pubid
int32 113k
27.9M
| question
stringlengths 17
664
| context
sequence | long_answer
stringlengths 1
3.34k
| final_decision
stringclasses 2
values | conversations
listlengths 2
2
|
|---|---|---|---|---|---|
18,564,130 | Does peroperative transrectal ultrasonography-guided bladder neck dissection ease the learning of robot-assisted laparoscopic prostatectomy? | {
"contexts": [
"To study the role of peroperative transrectal ultrasonography (peTRUS) for the dissection of the bladder neck during robot-assisted laparoscopic prostatectomy (RALP).",
"Integrated peTRUS in the da Vinci S system (Intuitive Surgical, Sunnyvale, CA, USA) was used for bladder neck identification and dissection in the initial 80 patients with clinically localized prostate cancer operated by two urologists. The clinical and pathological results were compared with the initial 80 patients who had RALP with no peTRUS. The location of positive margins was recorded.",
"The operative duration, blood loss, hospital stay, catheter dependency, clinical and pathological T-stage and Gleason sum score were no different between the groups. The prostate-specific antigen level at time of diagnosis was slightly higher for patients in the peTRUS group. Basal surgical margins (bladder neck and basal areas of both prostate lobes) were positive for tumour in 9.1% and 2.3% of patients treated without and with peTRUS, respectively (P = 0.001). Although the use of peTRUS improved the basal margin rate in the initial 30 patients in each group, it did not in the last 30 in each group, when the urologist's experience apparently improved. In a multivariate analysis the use of peTRUS and pathological T-stage were the best predictors of basal margin status. Pad use at 6 months after surgery was similar for both groups."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Blood Loss, Surgical",
"Clinical Competence",
"Humans",
"Laparoscopy",
"Length of Stay",
"Male",
"Middle Aged",
"Multivariate Analysis",
"Prostate-Specific Antigen",
"Prostatectomy",
"Prostatic Neoplasms",
"Retrospective Studies",
"Robotics",
"Ultrasonography, Interventional",
"Urinary Bladder",
"Urology"
]
} | peTRUS during RALP decreased the positive surgical margin rate at the base of the prostate during the initial experience of RALP. | yes | [
{
"from": "human",
"value": "Question: Does peroperative transrectal ultrasonography-guided bladder neck dissection ease the learning of robot-assisted laparoscopic prostatectomy?\nContext: {'contexts': ['To study the role of peroperative transrectal ultrasonography (peTRUS) for the dissection of the bladder neck during robot-assisted laparoscopic prostatectomy (RALP).', 'Integrated peTRUS in the da Vinci S system (Intuitive Surgical, Sunnyvale, CA, USA) was used for bladder neck identification and dissection in the initial 80 patients with clinically localized prostate cancer operated by two urologists. The clinical and pathological results were compared with the initial 80 patients who had RALP with no peTRUS. The location of positive margins was recorded.', \"The operative duration, blood loss, hospital stay, catheter dependency, clinical and pathological T-stage and Gleason sum score were no different between the groups. The prostate-specific antigen level at time of diagnosis was slightly higher for patients in the peTRUS group. Basal surgical margins (bladder neck and basal areas of both prostate lobes) were positive for tumour in 9.1% and 2.3% of patients treated without and with peTRUS, respectively (P = 0.001). Although the use of peTRUS improved the basal margin rate in the initial 30 patients in each group, it did not in the last 30 in each group, when the urologist's experience apparently improved. In a multivariate analysis the use of peTRUS and pathological T-stage were the best predictors of basal margin status. Pad use at 6 months after surgery was similar for both groups.\"], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Blood Loss, Surgical', 'Clinical Competence', 'Humans', 'Laparoscopy', 'Length of Stay', 'Male', 'Middle Aged', 'Multivariate Analysis', 'Prostate-Specific Antigen', 'Prostatectomy', 'Prostatic Neoplasms', 'Retrospective Studies', 'Robotics', 'Ultrasonography, Interventional', 'Urinary Bladder', 'Urology']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,572,230 | Do several distinct properties of the IgE repertoire determine effector cell degranulation in response to allergen challenge? | {
"contexts": [
"On cross-linking of receptor-bound IgE antibodies by allergens, effector cells (basophils and mast cells) involved in type I allergic reactions degranulate and release the potent chemical mediators stored inside their granules. Total and allergen-specific IgE concentrations, IgE affinity for allergen, and IgE clonality are all distinct properties of allergic patients' IgE repertoires. However, the inability to isolate individual IgE antibodies from allergic patients' sera presents a major barrier to understanding the importance of patient-specific IgE repertoires for the manifestation and severity of allergic symptoms.",
"We sought to investigate how individual properties of an IgE repertoire affect effector cell degranulation.",
"A panel of recombinant IgE (rIgE) antibodies specific for the major house dust mite allergen Der p 2 was developed and characterized in regard to Der p 2 affinity, as well as Der p 2 epitope specificity, by using surface plasmon resonance technology. Human basophils were sensitized with different combinations of rIgEs, and degranulation responses were measured by means of flow cytometry after challenge with Der p 2.",
"A total of 31 Der p 2-specific rIgEs were produced. They bound a total of 9 different Der p 2 epitopes in the affinity range (K(D) value) of 0.0358 to 291 nM. Factors increasing human basophil degranulation were increased total IgE concentrations, increased concentrations of allergen-specific IgE relative to non-allergen-specific IgE, more even concentration of individual allergen-specific IgE clones, increased IgE affinity for allergen, and increased number of allergen epitopes recognized by the IgE repertoire (increased IgE clonality)."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Antibody Affinity",
"Antibody Specificity",
"Antigens, Dermatophagoides",
"Arthropod Proteins",
"Basophils",
"Cell Degranulation",
"Cell Line",
"Epitope Mapping",
"Epitopes",
"Humans",
"Hypersensitivity, Immediate",
"Immunoglobulin E",
"Mast Cells",
"Recombinant Fusion Proteins"
]
} | This study demonstrates how distinct properties of the IgE repertoire, such as total and allergen-specific IgE antibody concentration, IgE affinity, and IgE clonality, affect effector cell degranulation. | yes | [
{
"from": "human",
"value": "Question: Do several distinct properties of the IgE repertoire determine effector cell degranulation in response to allergen challenge?\nContext: {'contexts': [\"On cross-linking of receptor-bound IgE antibodies by allergens, effector cells (basophils and mast cells) involved in type I allergic reactions degranulate and release the potent chemical mediators stored inside their granules. Total and allergen-specific IgE concentrations, IgE affinity for allergen, and IgE clonality are all distinct properties of allergic patients' IgE repertoires. However, the inability to isolate individual IgE antibodies from allergic patients' sera presents a major barrier to understanding the importance of patient-specific IgE repertoires for the manifestation and severity of allergic symptoms.\", 'We sought to investigate how individual properties of an IgE repertoire affect effector cell degranulation.', 'A panel of recombinant IgE (rIgE) antibodies specific for the major house dust mite allergen Der p 2 was developed and characterized in regard to Der p 2 affinity, as well as Der p 2 epitope specificity, by using surface plasmon resonance technology. Human basophils were sensitized with different combinations of rIgEs, and degranulation responses were measured by means of flow cytometry after challenge with Der p 2.', 'A total of 31 Der p 2-specific rIgEs were produced. They bound a total of 9 different Der p 2 epitopes in the affinity range (K(D) value) of 0.0358 to 291 nM. Factors increasing human basophil degranulation were increased total IgE concentrations, increased concentrations of allergen-specific IgE relative to non-allergen-specific IgE, more even concentration of individual allergen-specific IgE clones, increased IgE affinity for allergen, and increased number of allergen epitopes recognized by the IgE repertoire (increased IgE clonality).'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Antibody Affinity', 'Antibody Specificity', 'Antigens, Dermatophagoides', 'Arthropod Proteins', 'Basophils', 'Cell Degranulation', 'Cell Line', 'Epitope Mapping', 'Epitopes', 'Humans', 'Hypersensitivity, Immediate', 'Immunoglobulin E', 'Mast Cells', 'Recombinant Fusion Proteins']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,552,465 | Is insulin resistance the major determinant for microalbuminuria in severe hypertriglyceridemia : implication for high-risk stratification? | {
"contexts": [
"The significance of high triglyceride levels as a risk factor for coronary heart disease is uncertain. We hypothesized that oral glucose tolerance test (OGTT) and certain novel markers may help to identify high-risk patients.",
"We recruited 80 subjects with severe hypertriglyceridemia (age 27-73 years) without clinical proteinuria and diabetes mellitus (DM) which were diagnosed by fasting glucose <126 mg/dL from Hyperlipidemia Clinic of National Taiwan University Hospital for this study. We applied OGTT to evaluate occult DM and homeostasis model assessment (HOMA)-insulin resistance (IR) score to evaluate insulin resistance, and the measurements of microalbuminuria as a marker of vascular damage. In addition, serum or plasma markers of inflammation and fibrinolysis, fasting glucose and insulin as well as traditional cardiovascular risk factors were also evaluated.",
"The serum level of triglyceride was higher in patients with microalbuminuria than in those without (14.1+/-5.7 vs. 9.6+/-3.9 mmol/L, p=0.025). Patients with microalbuminuria had higher fasting blood glucose and insulin, higher post-OGTT glucose and insulin, higher prevalence of newly developed diabetes mellitus (DM) (39% vs. 11%, p=0.007) and higher HOMA-IR (6.2+/-4.4 vs. 3.3+/-2.0, p<0.001). Among all the inflammatory and fibrinolytic markers, only soluble intercellular adhesion molecule showed significant different between these two groups. Multiple logistic regression analysis showed that among the serum markers, only HOMA-IR level was significantly related to microalbuminuria."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Albuminuria",
"Biomarkers",
"Cohort Studies",
"Female",
"Fibrinolysis",
"Glucose Tolerance Test",
"Humans",
"Hypertriglyceridemia",
"Inflammation",
"Insulin Resistance",
"Male",
"Middle Aged",
"Odds Ratio",
"Prediabetic State",
"Risk Factors"
]
} | HOMA-IR is the major determinant for microalbuminuria in patients with severe hypertriglyceridemia. Impaired glucose metabolism is evident in patients with both severe hypertriglyceridemia and microalbuminuria. | yes | [
{
"from": "human",
"value": "Question: Is insulin resistance the major determinant for microalbuminuria in severe hypertriglyceridemia : implication for high-risk stratification?\nContext: {'contexts': ['The significance of high triglyceride levels as a risk factor for coronary heart disease is uncertain. We hypothesized that oral glucose tolerance test (OGTT) and certain novel markers may help to identify high-risk patients.', 'We recruited 80 subjects with severe hypertriglyceridemia (age 27-73 years) without clinical proteinuria and diabetes mellitus (DM) which were diagnosed by fasting glucose <126 mg/dL from Hyperlipidemia Clinic of National Taiwan University Hospital for this study. We applied OGTT to evaluate occult DM and homeostasis model assessment (HOMA)-insulin resistance (IR) score to evaluate insulin resistance, and the measurements of microalbuminuria as a marker of vascular damage. In addition, serum or plasma markers of inflammation and fibrinolysis, fasting glucose and insulin as well as traditional cardiovascular risk factors were also evaluated.', 'The serum level of triglyceride was higher in patients with microalbuminuria than in those without (14.1+/-5.7 vs. 9.6+/-3.9 mmol/L, p=0.025). Patients with microalbuminuria had higher fasting blood glucose and insulin, higher post-OGTT glucose and insulin, higher prevalence of newly developed diabetes mellitus (DM) (39% vs. 11%, p=0.007) and higher HOMA-IR (6.2+/-4.4 vs. 3.3+/-2.0, p<0.001). Among all the inflammatory and fibrinolytic markers, only soluble intercellular adhesion molecule showed significant different between these two groups. Multiple logistic regression analysis showed that among the serum markers, only HOMA-IR level was significantly related to microalbuminuria.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Albuminuria', 'Biomarkers', 'Cohort Studies', 'Female', 'Fibrinolysis', 'Glucose Tolerance Test', 'Humans', 'Hypertriglyceridemia', 'Inflammation', 'Insulin Resistance', 'Male', 'Middle Aged', 'Odds Ratio', 'Prediabetic State', 'Risk Factors']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,564,000 | Are fecal calprotectin concentrations higher in exclusively breastfed infants compared to those who are mixed-fed? | {
"contexts": [
"Previous studies have shown that giving other foods while breastfeeding increases the risk of mother-to-child transmission of human immunodeficiency virus (HIV) type 1. The mechanism is speculated to be increased inflammation of the gastrointestinal tract.",
"In a prospective longitudinal study, we compared fecal calprotectin, a marker of intestinal inflammatory disease, in healthy U.S. infants 0-6 months of age who were exclusively breastfed compared to those given additional liquids or solids.",
"In comparison to infants who were mixed-fed, fecal calprotectin was significantly higher in the exclusively breastfed group (p = 0.01) by a mean of 60 mg/kg (SE = 23)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Biomarkers",
"Bottle Feeding",
"Breast Feeding",
"Feces",
"Female",
"HIV Infections",
"HIV-1",
"Humans",
"Infant",
"Infant Food",
"Infant, Newborn",
"Infectious Disease Transmission, Vertical",
"Inflammatory Bowel Diseases",
"Leukocyte L1 Antigen Complex",
"Longitudinal Studies",
"Male",
"Prospective Studies",
"Risk Factors",
"Weaning"
]
} | Introducing complementary food does not increase intestinal inflammation according to this marker. Studies to assess fecal calprotectin levels in breastfeeding and mixed-fed infants born to HIV-infected mothers living in resource-constrained settings, and to evaluate potential protective effects of calprotectin in early infancy, are recommended in the continuing effort to elucidate the mechanisms responsible for increased risk of HIV transmission through mixed-feeding. | yes | [
{
"from": "human",
"value": "Question: Are fecal calprotectin concentrations higher in exclusively breastfed infants compared to those who are mixed-fed?\nContext: {'contexts': ['Previous studies have shown that giving other foods while breastfeeding increases the risk of mother-to-child transmission of human immunodeficiency virus (HIV) type 1. The mechanism is speculated to be increased inflammation of the gastrointestinal tract.', 'In a prospective longitudinal study, we compared fecal calprotectin, a marker of intestinal inflammatory disease, in healthy U.S. infants 0-6 months of age who were exclusively breastfed compared to those given additional liquids or solids.', 'In comparison to infants who were mixed-fed, fecal calprotectin was significantly higher in the exclusively breastfed group (p = 0.01) by a mean of 60 mg/kg (SE = 23).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Biomarkers', 'Bottle Feeding', 'Breast Feeding', 'Feces', 'Female', 'HIV Infections', 'HIV-1', 'Humans', 'Infant', 'Infant Food', 'Infant, Newborn', 'Infectious Disease Transmission, Vertical', 'Inflammatory Bowel Diseases', 'Leukocyte L1 Antigen Complex', 'Longitudinal Studies', 'Male', 'Prospective Studies', 'Risk Factors', 'Weaning']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,542,929 | Does epinephrine administration at birth prevent long-term changes in dopaminergic parameters caused by Cesarean section birth in the rat? | {
"contexts": [
"Obstetric complications involving birth hypoxia are implicated in the etiology of disorders with dopaminergic dysfunction, such as schizophrenia. Cesarean section (C-section) birth in both humans and rats is associated with increased mild respiratory distress and with reduced levels of circulating catecholamines at birth, which normally serve to prime the lungs and activate other processes promoting extrauterine adaptation. Using a rat model, it has been found that C-section birth can produce long-term changes in central nervous system (CNS) dopamine function, compared to vaginal birth.",
"The present experiments tested if administering exogenous epinephrine at birth could reverse long-term changes in dopaminergic parameters in C-sectioned rats.",
"In the absence of stress at adulthood, no differences were observed between C-sectioned and vaginally born rats in levels of in vivo tyrosine hydroxylase (TH) activity and dopamine transporter (DAT) binding. However, after repeated mild stress at adulthood, C-sectioned rats showed increased TH activity in nucleus accumbens and increased DAT in dorsal striatum and accumbens, compared to vaginally born controls. A single injection of epinephrine to C-sectioned rats just after birth prevented the increased TH activity and DAT binding seen in C-sectioned rats after repeated mild stress at adulthood. There was also a trend for epinephrine at birth to partially reverse an increase in amphetamine-induced locomotion seen in C-sectioned rats at adulthood."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"RESULTS"
],
"meshes": [
"Age Factors",
"Amphetamine",
"Animals",
"Arousal",
"Cesarean Section",
"Corpus Striatum",
"Dopamine",
"Dopamine Plasma Membrane Transport Proteins",
"Epinephrine",
"Female",
"Motor Activity",
"Nucleus Accumbens",
"Pregnancy",
"Rats",
"Social Isolation",
"Tyrosine 3-Monooxygenase"
]
} | These results suggest that variations in levels of circulating catecholamines in the neonate at the time of birth could contribute to subtle long-term changes in CNS function. | yes | [
{
"from": "human",
"value": "Question: Does epinephrine administration at birth prevent long-term changes in dopaminergic parameters caused by Cesarean section birth in the rat?\nContext: {'contexts': ['Obstetric complications involving birth hypoxia are implicated in the etiology of disorders with dopaminergic dysfunction, such as schizophrenia. Cesarean section (C-section) birth in both humans and rats is associated with increased mild respiratory distress and with reduced levels of circulating catecholamines at birth, which normally serve to prime the lungs and activate other processes promoting extrauterine adaptation. Using a rat model, it has been found that C-section birth can produce long-term changes in central nervous system (CNS) dopamine function, compared to vaginal birth.', 'The present experiments tested if administering exogenous epinephrine at birth could reverse long-term changes in dopaminergic parameters in C-sectioned rats.', 'In the absence of stress at adulthood, no differences were observed between C-sectioned and vaginally born rats in levels of in vivo tyrosine hydroxylase (TH) activity and dopamine transporter (DAT) binding. However, after repeated mild stress at adulthood, C-sectioned rats showed increased TH activity in nucleus accumbens and increased DAT in dorsal striatum and accumbens, compared to vaginally born controls. A single injection of epinephrine to C-sectioned rats just after birth prevented the increased TH activity and DAT binding seen in C-sectioned rats after repeated mild stress at adulthood. There was also a trend for epinephrine at birth to partially reverse an increase in amphetamine-induced locomotion seen in C-sectioned rats at adulthood.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'RESULTS'], 'meshes': ['Age Factors', 'Amphetamine', 'Animals', 'Arousal', 'Cesarean Section', 'Corpus Striatum', 'Dopamine', 'Dopamine Plasma Membrane Transport Proteins', 'Epinephrine', 'Female', 'Motor Activity', 'Nucleus Accumbens', 'Pregnancy', 'Rats', 'Social Isolation', 'Tyrosine 3-Monooxygenase']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,542,920 | Are central venous to mixed venous blood oxygen and lactate gradients associated with outcome in critically ill patients? | {
"contexts": [
"Blood O(2) saturation and lactate concentration gradients from superior vena cava (SVC) to pulmonary artery (PA) occur in critically ill patients. These gradients (DeltaSO(2) and Delta[Lac]) may be positive or negative. We tested the hypothesis that positive DeltaSO(2) and Delta[Lac] are associated with improved survival in critically ill patients.",
"Multinational, prospective observational study conducted in six medical and surgical ICUs.",
"Consecutive sample of 106 adults requiring insertion of a pulmonary artery catheter (PAC). Average age was 59.5 +/- 15.5 years, APACHE II score was 15.5 +/- 6.7 (mean +/- SD). Main outcome measure was 28-day mortality.",
"None.",
"We drew blood samples from the proximal and distal ports of PACs every 6 h from the time of PAC insertion (Initial measurement) until its removal (Final measurement). Samples were analyzed for SO(2), [Lac], glucose concentration and blood gases. Hemodynamic measurements were obtained after blood samples. We monitored patients for 30.9 +/- 11.0 h. Overall mortality rate was 25.5%. More survivors had mean and final DeltaSO(2) > or = 0 and Delta[Lac] > or = 0 than decedents (p < 0.01; p < 0.05 respectively). On the average, DeltaSO(2) and Delta[Lac] were positive in survivors and negative in decedents. Survival odds ratios for final measurements of DeltaSO(2) > or = 0 and Delta[Lac] > or = 0 were 19.22 and 7.70, respectively (p < 0.05)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"APACHE",
"Catheterization, Central Venous",
"Critical Illness",
"Female",
"Hemodynamics",
"Humans",
"Intensive Care Units",
"Lactates",
"Logistic Models",
"Male",
"Middle Aged",
"Oxygen",
"Postoperative Complications",
"Predictive Value of Tests",
"Sepsis",
"Survival Analysis"
]
} | A strong association exists between positive DeltaSO(2) and Delta[Lac] and survival in critically ill patients. Whether therapy aimed at increasing DeltaSO(2) and Delta[Lac] results in improved ICU survival remains to be determined. | yes | [
{
"from": "human",
"value": "Question: Are central venous to mixed venous blood oxygen and lactate gradients associated with outcome in critically ill patients?\nContext: {'contexts': ['Blood O(2) saturation and lactate concentration gradients from superior vena cava (SVC) to pulmonary artery (PA) occur in critically ill patients. These gradients (DeltaSO(2) and Delta[Lac]) may be positive or negative. We tested the hypothesis that positive DeltaSO(2) and Delta[Lac] are associated with improved survival in critically ill patients.', 'Multinational, prospective observational study conducted in six medical and surgical ICUs.', 'Consecutive sample of 106 adults requiring insertion of a pulmonary artery catheter (PAC). Average age was 59.5 +/- 15.5 years, APACHE II score was 15.5 +/- 6.7 (mean +/- SD). Main outcome measure was 28-day mortality.', 'None.', 'We drew blood samples from the proximal and distal ports of PACs every 6 h from the time of PAC insertion (Initial measurement) until its removal (Final measurement). Samples were analyzed for SO(2), [Lac], glucose concentration and blood gases. Hemodynamic measurements were obtained after blood samples. We monitored patients for 30.9 +/- 11.0 h. Overall mortality rate was 25.5%. More survivors had mean and final DeltaSO(2) > or = 0 and Delta[Lac] > or = 0 than decedents (p < 0.01; p < 0.05 respectively). On the average, DeltaSO(2) and Delta[Lac] were positive in survivors and negative in decedents. Survival odds ratios for final measurements of DeltaSO(2) > or = 0 and Delta[Lac] > or = 0 were 19.22 and 7.70, respectively (p < 0.05).'], 'labels': ['OBJECTIVE', 'METHODS', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['APACHE', 'Catheterization, Central Venous', 'Critical Illness', 'Female', 'Hemodynamics', 'Humans', 'Intensive Care Units', 'Lactates', 'Logistic Models', 'Male', 'Middle Aged', 'Oxygen', 'Postoperative Complications', 'Predictive Value of Tests', 'Sepsis', 'Survival Analysis']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,565,254 | Does anti-TNF-alpha therapy modulate resistin in patients with rheumatoid arthritis? | {
"contexts": [
"Chronic systemic inflammation plays a pivotal role in the development of atherosclerosis in rheumatoid arthritis (RA). In the present study, we investigated whether anti-TNF-alpha antagonist-monoclonal antibody-infliximab administration alters circulating levels of resistin, a proinflammatory adipokine. We further assessed associations of circulating resistin concentrations with CRP and ESR levels, platelet counts and metabolic syndrome and demographic characteristics in RA patients on periodical treatment with infliximab.",
"We investigated 33 patients with RA on periodical treatment with infliximab. Serum resistin levels were determined immediately prior to and after infliximab infusion.",
"Upon infliximab administration, mean (SD) serum resistin concentrations (ng/ml) decreased from 21.9 (9.9) to 17.4 (8.9) (p=0.005). Also, a significant association between the mean ESR (r=0.405; p=0.03) and CRP (r=0.571; p=0.0005) from disease diagnosis and ESR (r=0.486; p=0.004), CRP (r=0.599; p=0.0005) and platelet count (r=0.559; p=0.0007) at the time of the study and baseline resistin levels was found."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Antibodies, Monoclonal",
"Antirheumatic Agents",
"Arthritis, Rheumatoid",
"Biomarkers",
"Blood Sedimentation",
"C-Reactive Protein",
"Female",
"Humans",
"Infliximab",
"Male",
"Middle Aged",
"Resistin",
"Tumor Necrosis Factor-alpha"
]
} | The present study shows that anti-TNF-alpha therapy results in a rapid reduction of serum resistin levels in patients with RA. It also confirms a close association between laboratory markers of inflammation, particularly CRP and resistin levels. These observations support a potential role of resistin in the inflammatory cascade in RA. | yes | [
{
"from": "human",
"value": "Question: Does anti-TNF-alpha therapy modulate resistin in patients with rheumatoid arthritis?\nContext: {'contexts': ['Chronic systemic inflammation plays a pivotal role in the development of atherosclerosis in rheumatoid arthritis (RA). In the present study, we investigated whether anti-TNF-alpha antagonist-monoclonal antibody-infliximab administration alters circulating levels of resistin, a proinflammatory adipokine. We further assessed associations of circulating resistin concentrations with CRP and ESR levels, platelet counts and metabolic syndrome and demographic characteristics in RA patients on periodical treatment with infliximab.', 'We investigated 33 patients with RA on periodical treatment with infliximab. Serum resistin levels were determined immediately prior to and after infliximab infusion.', 'Upon infliximab administration, mean (SD) serum resistin concentrations (ng/ml) decreased from 21.9 (9.9) to 17.4 (8.9) (p=0.005). Also, a significant association between the mean ESR (r=0.405; p=0.03) and CRP (r=0.571; p=0.0005) from disease diagnosis and ESR (r=0.486; p=0.004), CRP (r=0.599; p=0.0005) and platelet count (r=0.559; p=0.0007) at the time of the study and baseline resistin levels was found.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Antibodies, Monoclonal', 'Antirheumatic Agents', 'Arthritis, Rheumatoid', 'Biomarkers', 'Blood Sedimentation', 'C-Reactive Protein', 'Female', 'Humans', 'Infliximab', 'Male', 'Middle Aged', 'Resistin', 'Tumor Necrosis Factor-alpha']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,565,255 | Does methotrexate selectively modulate TH1/TH2 balance in active rheumatoid arthritis patients? | {
"contexts": [
"The mechanism by which low dose methotrexate (MTX, the gold standard treatment for rheumatoid arthritis) exerts its anti-inflammatory effect in rheumatoid arthritis (RA) patients is still debated. Lately, the MTX immunosuppressive effect has been related to apoptosis, especially in active RA patients, with ROS involvement.",
"In the present research we investigated MTX oxidative effect and its ability to modulate immune balance in active versus non-active RA patients.",
"Our results show that MTX induces IL-10 secretion (a TH2 cytokine) and significantly reduces TH1 profile in Peripheral Mononuclear Cells (PMNC) derived from active RA patients (n=28). Additionally, we found that MTX modulates the immune status towards TH2 dominance by decreasing the IL-12R and the CXCR3 receptors typical for the TH1 population. Moreover, MTX was found to inhibit the production of nitric oxide (NO) in these patients, a phenomenon that might contribute to MTX action toward cytokine homeostasis. A significant correlation was found between MTX IL-10 induction and NO inhibition in active RA patients."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Acute Disease",
"Antirheumatic Agents",
"Apoptosis",
"Arthritis, Rheumatoid",
"Humans",
"Interleukin-10",
"Methotrexate",
"Nitric Oxide",
"Reactive Oxygen Species",
"Receptors, CXCR3",
"Receptors, Interleukin-12",
"Th1 Cells",
"Th2 Cells"
]
} | Our data suggest that, in active RA patients, apoptosis induction by MTX may be primarily due to IL-10 production via modulation of oxidative stress, which may restore the critically important immune balance. These findings may contribute to determining which group of RA patients may better respond to MTX therapy. | yes | [
{
"from": "human",
"value": "Question: Does methotrexate selectively modulate TH1/TH2 balance in active rheumatoid arthritis patients?\nContext: {'contexts': ['The mechanism by which low dose methotrexate (MTX, the gold standard treatment for rheumatoid arthritis) exerts its anti-inflammatory effect in rheumatoid arthritis (RA) patients is still debated. Lately, the MTX immunosuppressive effect has been related to apoptosis, especially in active RA patients, with ROS involvement.', 'In the present research we investigated MTX oxidative effect and its ability to modulate immune balance in active versus non-active RA patients.', 'Our results show that MTX induces IL-10 secretion (a TH2 cytokine) and significantly reduces TH1 profile in Peripheral Mononuclear Cells (PMNC) derived from active RA patients (n=28). Additionally, we found that MTX modulates the immune status towards TH2 dominance by decreasing the IL-12R and the CXCR3 receptors typical for the TH1 population. Moreover, MTX was found to inhibit the production of nitric oxide (NO) in these patients, a phenomenon that might contribute to MTX action toward cytokine homeostasis. A significant correlation was found between MTX IL-10 induction and NO inhibition in active RA patients.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Acute Disease', 'Antirheumatic Agents', 'Apoptosis', 'Arthritis, Rheumatoid', 'Humans', 'Interleukin-10', 'Methotrexate', 'Nitric Oxide', 'Reactive Oxygen Species', 'Receptors, CXCR3', 'Receptors, Interleukin-12', 'Th1 Cells', 'Th2 Cells']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,565,252 | Is the differential expression of osteoprotegerin ( OPG ) and receptor activator of nuclear factor kappaB ligand ( RANKL ) in human osteoarthritic subchondral bone osteoblasts an indicator of the metabolic state of these disease cells? | {
"contexts": [
"We previously reported that human OA subchondral bone osteoblasts could be discriminated into two subpopulations identified by their levels of endogenous production (low [L] or high [H]) of PGE(2). Here, we investigated the OPG and RANKL expression levels, the histologic analysis of the subchondral bone as well as the osteoclast differentiation effect of osteoblasts on normal and both OA subpopulations (L and H), and further examined on the L OA osteoblasts the modulation of bone remodelling factors on the OPG and RANKL levels, as well as on the resorption activity.",
"Gene expression was determined using real-time PCR, PGE2 and OPG levels by specific ELISA, and membranous RANKL by flow cytometry. Histological observation of the subchondral bone was performed on human knee specimens. Osteoclast differentiation and formation was assayed by using the pre-osteoclastic cell line RAW 264.7. OPG and RANKL modulation on L OA osteoblasts was monitored following treatment with osteotropic factors, and the resorption activity was studied by the co-culture of differentiated PBMC/osteoblasts.",
"Human OA subchondral bone osteoblasts expressed less OPG than normal. Compared to normal, RANKL gene expression levels were increased in L OA and decreased in H OA cells. The OPG/RANKL mRNA ratio was significantly diminished in L OA compared to normal or H OA (p<0.02, p<0.03), and markedly increased in H OA compared to normal. Inhibition of endogenous PGE(2) levels by indomethacin markedly decreased the ratio of OPG/RANKL on the H OA. In contrast to H OA osteoblasts, L OA cells induced a significantly higher level of osteoclast differentiation and formation (p<0.05). Histological analysis showed a reduced subchondral bone on the L OA and an increased bone mass on the H OA compared to normal. Treatment of L OA osteoblasts with osteotropic factors revealed that the OPG/RANKL mRNA expression ratio was significantly reduced by vitamin D(3) and significantly increased by TNF-alpha, PTH and PGE(2), while IL-1Beta demonstrated no effect. OPG protein levels showed similar profiles. No true effect was noted on membranous RANKL upon treatment with IL-1Beta, PGE(2) and PTH, but a significant increase was observed with vitamin D3 and TNF-alpha. The resorption activity of the L OA cells was significantly inhibited by all treatments except IL-1Beta, with maximum effect observed with vitamin D(3) and PGE(2)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Aged, 80 and over",
"Bone Resorption",
"Cartilage, Articular",
"Cell Differentiation",
"Dinoprostone",
"Energy Metabolism",
"Enzyme-Linked Immunosorbent Assay",
"Femur",
"Humans",
"Middle Aged",
"Osteoarthritis, Knee",
"Osteoblasts",
"Osteoclasts",
"Osteoprotegerin",
"RANK Ligand",
"Reverse Transcriptase Polymerase Chain Reaction"
]
} | OPG and RANKL levels, and consequently the OPG/RANKL ratio, differed according to human OA subchondral bone osteoblast classification; it is decreased in L and increased in H OA. These findings, in addition to those showing that L OA osteoblasts have a reduced subchondral bone mass and induce a higher level of osteoclast differentiation, strongly suggest that the metabolic state of the L OA osteoblasts favours bone resorption. | yes | [
{
"from": "human",
"value": "Question: Is the differential expression of osteoprotegerin ( OPG ) and receptor activator of nuclear factor kappaB ligand ( RANKL ) in human osteoarthritic subchondral bone osteoblasts an indicator of the metabolic state of these disease cells?\nContext: {'contexts': ['We previously reported that human OA subchondral bone osteoblasts could be discriminated into two subpopulations identified by their levels of endogenous production (low [L] or high [H]) of PGE(2). Here, we investigated the OPG and RANKL expression levels, the histologic analysis of the subchondral bone as well as the osteoclast differentiation effect of osteoblasts on normal and both OA subpopulations (L and H), and further examined on the L OA osteoblasts the modulation of bone remodelling factors on the OPG and RANKL levels, as well as on the resorption activity.', 'Gene expression was determined using real-time PCR, PGE2 and OPG levels by specific ELISA, and membranous RANKL by flow cytometry. Histological observation of the subchondral bone was performed on human knee specimens. Osteoclast differentiation and formation was assayed by using the pre-osteoclastic cell line RAW 264.7. OPG and RANKL modulation on L OA osteoblasts was monitored following treatment with osteotropic factors, and the resorption activity was studied by the co-culture of differentiated PBMC/osteoblasts.', 'Human OA subchondral bone osteoblasts expressed less OPG than normal. Compared to normal, RANKL gene expression levels were increased in L OA and decreased in H OA cells. The OPG/RANKL mRNA ratio was significantly diminished in L OA compared to normal or H OA (p<0.02, p<0.03), and markedly increased in H OA compared to normal. Inhibition of endogenous PGE(2) levels by indomethacin markedly decreased the ratio of OPG/RANKL on the H OA. In contrast to H OA osteoblasts, L OA cells induced a significantly higher level of osteoclast differentiation and formation (p<0.05). Histological analysis showed a reduced subchondral bone on the L OA and an increased bone mass on the H OA compared to normal. Treatment of L OA osteoblasts with osteotropic factors revealed that the OPG/RANKL mRNA expression ratio was significantly reduced by vitamin D(3) and significantly increased by TNF-alpha, PTH and PGE(2), while IL-1Beta demonstrated no effect. OPG protein levels showed similar profiles. No true effect was noted on membranous RANKL upon treatment with IL-1Beta, PGE(2) and PTH, but a significant increase was observed with vitamin D3 and TNF-alpha. The resorption activity of the L OA cells was significantly inhibited by all treatments except IL-1Beta, with maximum effect observed with vitamin D(3) and PGE(2).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Aged, 80 and over', 'Bone Resorption', 'Cartilage, Articular', 'Cell Differentiation', 'Dinoprostone', 'Energy Metabolism', 'Enzyme-Linked Immunosorbent Assay', 'Femur', 'Humans', 'Middle Aged', 'Osteoarthritis, Knee', 'Osteoblasts', 'Osteoclasts', 'Osteoprotegerin', 'RANK Ligand', 'Reverse Transcriptase Polymerase Chain Reaction']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,559,244 | Does [ Electroacupuncture protect the brain against acute ischemic injury via up-regulation of delta-opioid receptor in rats ]? | {
"contexts": [
"To explore the effect of delta-opioid receptor (DOR) in electroacupuncture (EA) protecting the brain against acute ischemic injury.",
"Fifty-one rats were randomly divided into sham ischemia group, ischemia group, sham EA group, EA group, and EA+DOR antagonist (naltrindole) group. Transient focal cerebral ischemia (1 hour) was induced in rat brain by middle cerebral artery occlusion (MCAO) method. EA was applied on Shuigou (GV 26) and Neiguan (PC 6) for 30 min, starting immediately after the onset of reperfusion. Neurological deficit scores and volume of cerebral infarction were detected after 24-hour reperfusion. Other 12 rats were randomly divided into sham ischemia group, ischemia group, EA group and EA + naltrindole group. DOR protein expressions were assessed by Western blotting after 24-hour reperfusion.",
"In comparison with the ischemia group and sham EA group, EA significantly reduced ischemic infarction and neurological deficits (P<0.05); EA significantly increased the expression of 60 kD DOR protein (P<0.05) and tended to increase that of 36 kD DOR protein (P>0.05). When naltrindole was combined with EA, the naltrindole completely abolished the EA-induced protection in ischemic infarction and neurological deficits, and also arrested the expression of DOR."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Electroacupuncture",
"Infarction, Middle Cerebral Artery",
"Male",
"Random Allocation",
"Rats",
"Rats, Sprague-Dawley",
"Receptors, Opioid, delta",
"Reperfusion Injury",
"Up-Regulation"
]
} | EA can up-regulate DOR expression and protect the brain from ischemia-reperfusion injury. | yes | [
{
"from": "human",
"value": "Question: Does [ Electroacupuncture protect the brain against acute ischemic injury via up-regulation of delta-opioid receptor in rats ]?\nContext: {'contexts': ['To explore the effect of delta-opioid receptor (DOR) in electroacupuncture (EA) protecting the brain against acute ischemic injury.', 'Fifty-one rats were randomly divided into sham ischemia group, ischemia group, sham EA group, EA group, and EA+DOR antagonist (naltrindole) group. Transient focal cerebral ischemia (1 hour) was induced in rat brain by middle cerebral artery occlusion (MCAO) method. EA was applied on Shuigou (GV 26) and Neiguan (PC 6) for 30 min, starting immediately after the onset of reperfusion. Neurological deficit scores and volume of cerebral infarction were detected after 24-hour reperfusion. Other 12 rats were randomly divided into sham ischemia group, ischemia group, EA group and EA + naltrindole group. DOR protein expressions were assessed by Western blotting after 24-hour reperfusion.', 'In comparison with the ischemia group and sham EA group, EA significantly reduced ischemic infarction and neurological deficits (P<0.05); EA significantly increased the expression of 60 kD DOR protein (P<0.05) and tended to increase that of 36 kD DOR protein (P>0.05). When naltrindole was combined with EA, the naltrindole completely abolished the EA-induced protection in ischemic infarction and neurological deficits, and also arrested the expression of DOR.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Electroacupuncture', 'Infarction, Middle Cerebral Artery', 'Male', 'Random Allocation', 'Rats', 'Rats, Sprague-Dawley', 'Receptors, Opioid, delta', 'Reperfusion Injury', 'Up-Regulation']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,551,036 | Is disposition of ezetimibe influenced by polymorphisms of the hepatic uptake carrier OATP1B1? | {
"contexts": [
"Genetic variability in hepatic uptake was recently shown to influence the disposition and cholesterol-lowering effects of statins. Ezetimibe, an inhibitor of the intestinal cholesterol uptake protein Niemann-Pick C 1 like 1, is another drug for which genetic polymorphisms of hepatic organic anion transporting polypeptides (OATPs) are expected to be of clinical relevance because ezetimibe undergoes intensive enterohepatic circulation for which hepatic uptake transporters may be rate-limiting determinants.",
"Using OATP1B3-, OATP2B1-, and OATP1B1-transfected HEK cells, including the OATP1B1 variants OATP1B1*1b and OATP1B1*5, we measured the uptake of ezetimibe and its glucuronide and we analyzed the competition with the common OATP-substrate bromosulfophthalein. Disposition and sterol-lowering effects of 20-mg ezetimibe were measured in 35 healthy participants genotyped for OATP1B1, ABCB1, ABCC2, and UGT1A1.",
"Ezetimibe glucuronide inhibited bromosulfophthalein uptake in all OATP-transfected cells (50% inhibitory concentration (IC50): 0.14-0.26 mumol/l) whereas ezetimibe was 30-100 times less potent. Only the glucuronide was accumulated significantly in cells expressing OATP1B1 and OATP2B1. Its uptake in cells expressing OATP1B1*1b and *5 was reduced. In-vivo studies showed there was a gene-dose-dependent decrease in the area under the curve of ezetimibe in participants with the OATP1B1*1b protein (*1a/*1a, N=12, 112+/-66 ngxh/ml vs. *1a/*1b, N=8, 88+/-39 ngxh/ml vs. *1b/*1b, N=5, 55+/-18 ngxh/ml; Jonkheere-Terpstra, P=0.041) and a tendency for increased glucuronide exposure (704+/-296 vs. 878+/-369 vs. 1059+/-363 ngxh/ml; P=0.092). Fecal ezetimibe excretion was significantly decreased whereas renal glucuronide excretion was increased in carriers of *1b/*1b. Fecal excretion was also diminished in carriers of OATP1B1*5 and *15. The sterol-lowering effect of ezetimibe was not influenced by OATP1B1 polymorphisms."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Azetidines",
"Cells, Cultured",
"Ezetimibe",
"Female",
"Genotype",
"Humans",
"Inactivation, Metabolic",
"Liver",
"Liver-Specific Organic Anion Transporter 1",
"Male",
"Organic Anion Transporters",
"Polymorphism, Single Nucleotide",
"Sterols",
"Sulfobromophthalein"
]
} | Pharmacokinetics of ezetimibe is influenced by OATP1B1 polymorphisms in healthy participants after single dose administration. | yes | [
{
"from": "human",
"value": "Question: Is disposition of ezetimibe influenced by polymorphisms of the hepatic uptake carrier OATP1B1?\nContext: {'contexts': ['Genetic variability in hepatic uptake was recently shown to influence the disposition and cholesterol-lowering effects of statins. Ezetimibe, an inhibitor of the intestinal cholesterol uptake protein Niemann-Pick C 1 like 1, is another drug for which genetic polymorphisms of hepatic organic anion transporting polypeptides (OATPs) are expected to be of clinical relevance because ezetimibe undergoes intensive enterohepatic circulation for which hepatic uptake transporters may be rate-limiting determinants.', 'Using OATP1B3-, OATP2B1-, and OATP1B1-transfected HEK cells, including the OATP1B1 variants OATP1B1*1b and OATP1B1*5, we measured the uptake of ezetimibe and its glucuronide and we analyzed the competition with the common OATP-substrate bromosulfophthalein. Disposition and sterol-lowering effects of 20-mg ezetimibe were measured in 35 healthy participants genotyped for OATP1B1, ABCB1, ABCC2, and UGT1A1.', 'Ezetimibe glucuronide inhibited bromosulfophthalein uptake in all OATP-transfected cells (50% inhibitory concentration (IC50): 0.14-0.26 mumol/l) whereas ezetimibe was 30-100 times less potent. Only the glucuronide was accumulated significantly in cells expressing OATP1B1 and OATP2B1. Its uptake in cells expressing OATP1B1*1b and *5 was reduced. In-vivo studies showed there was a gene-dose-dependent decrease in the area under the curve of ezetimibe in participants with the OATP1B1*1b protein (*1a/*1a, N=12, 112+/-66 ngxh/ml vs. *1a/*1b, N=8, 88+/-39 ngxh/ml vs. *1b/*1b, N=5, 55+/-18 ngxh/ml; Jonkheere-Terpstra, P=0.041) and a tendency for increased glucuronide exposure (704+/-296 vs. 878+/-369 vs. 1059+/-363 ngxh/ml; P=0.092). Fecal ezetimibe excretion was significantly decreased whereas renal glucuronide excretion was increased in carriers of *1b/*1b. Fecal excretion was also diminished in carriers of OATP1B1*5 and *15. The sterol-lowering effect of ezetimibe was not influenced by OATP1B1 polymorphisms.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Azetidines', 'Cells, Cultured', 'Ezetimibe', 'Female', 'Genotype', 'Humans', 'Inactivation, Metabolic', 'Liver', 'Liver-Specific Organic Anion Transporter 1', 'Male', 'Organic Anion Transporters', 'Polymorphism, Single Nucleotide', 'Sterols', 'Sulfobromophthalein']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,551,039 | Is common variation in the NOS1AP gene associated with reduced glucose-lowering effect and with increased mortality in users of sulfonylurea? | {
"contexts": [
"The single nucleotide polymorphism rs10494366 in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene is associated with QTc prolongation, through an effect on the intracellular Ca levels. As sulfonylurea stimulate insulin secretion by an increased influx of Ca, we hypothesized that this polymorphism is associated with the glucose-lowering effect and mortality risk in sulfonylurea users.",
"Associations between the NOS1AP polymorphism, prescribed doses, and mortality rates in sulfonylurea, metformin, and insulin users were assessed in the Rotterdam Study, a population-based cohort study of 7983 elderly people.",
"We identified 619 participants who were prescribed oral antidiabetic drugs during follow-up. In glibenclamide users carrying the TG genotype, the prescribed doses were higher compared with the glibenclamide users carrying the TT genotype [0.38 defined daily dose units, 95% confidence interval (CI) 0.14-0.63]. Glibenclamide users with the TG or GG genotype had an increased mortality risk compared with glibenclamide users with the TT genotype [hazard ratio (HR) 2.80, 95% CI: 1.09-7.22]. Tolbutamide users with the TG or GG genotype (HR: 0.30, 95% CI: 0.14-0.63) and glimepiride users with the TG or GG genotype (HR: 0.18, 95% CI: 0.04-0.74) had a decreased mortality risk compared with tolbutamide and glimepiride users with the TT genotype."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adaptor Proteins, Signal Transducing",
"Aged",
"Aged, 80 and over",
"Blood Glucose",
"Cohort Studies",
"Diabetes Mellitus, Type 2",
"Drug Resistance",
"Female",
"Follow-Up Studies",
"Genotype",
"Humans",
"Hypoglycemic Agents",
"Male",
"Middle Aged",
"Polymorphism, Single Nucleotide",
"Sulfonylurea Compounds",
"Survival Analysis"
]
} | In participants with the TG or GG genotype at rs10494366 in the NOS1AP gene, glibenclamide is less effective in reducing glucose levels and mortality rates were higher compared with glibenclamide users with the TT genotype. In tolbutamide and glimepiride users, the TG and GG genotype were associated with a reduced mortality rate. | yes | [
{
"from": "human",
"value": "Question: Is common variation in the NOS1AP gene associated with reduced glucose-lowering effect and with increased mortality in users of sulfonylurea?\nContext: {'contexts': ['The single nucleotide polymorphism rs10494366 in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene is associated with QTc prolongation, through an effect on the intracellular Ca levels. As sulfonylurea stimulate insulin secretion by an increased influx of Ca, we hypothesized that this polymorphism is associated with the glucose-lowering effect and mortality risk in sulfonylurea users.', 'Associations between the NOS1AP polymorphism, prescribed doses, and mortality rates in sulfonylurea, metformin, and insulin users were assessed in the Rotterdam Study, a population-based cohort study of 7983 elderly people.', 'We identified 619 participants who were prescribed oral antidiabetic drugs during follow-up. In glibenclamide users carrying the TG genotype, the prescribed doses were higher compared with the glibenclamide users carrying the TT genotype [0.38 defined daily dose units, 95% confidence interval (CI) 0.14-0.63]. Glibenclamide users with the TG or GG genotype had an increased mortality risk compared with glibenclamide users with the TT genotype [hazard ratio (HR) 2.80, 95% CI: 1.09-7.22]. Tolbutamide users with the TG or GG genotype (HR: 0.30, 95% CI: 0.14-0.63) and glimepiride users with the TG or GG genotype (HR: 0.18, 95% CI: 0.04-0.74) had a decreased mortality risk compared with tolbutamide and glimepiride users with the TT genotype.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adaptor Proteins, Signal Transducing', 'Aged', 'Aged, 80 and over', 'Blood Glucose', 'Cohort Studies', 'Diabetes Mellitus, Type 2', 'Drug Resistance', 'Female', 'Follow-Up Studies', 'Genotype', 'Humans', 'Hypoglycemic Agents', 'Male', 'Middle Aged', 'Polymorphism, Single Nucleotide', 'Sulfonylurea Compounds', 'Survival Analysis']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,551,038 | Does altered expression of methylenetetrahydrofolate reductase modify response to methotrexate in mice? | {
"contexts": [
"Folates provide one-carbon units for nucleotide synthesis and methylation reactions. A common polymorphism (677C-->T) in methylenetetrahydrofolate reductase (MTHFR) encodes an enzyme with reduced activity. Response to the antifolate methotrexate (MTX) may be modified in 677TT individuals because MTHFR converts nonmethylated folates, used for thymidine and purine synthesis, to 5-methyltetrahydrofolate, used in homocysteine remethylation to methionine. To study potential interactions between MTHFR activity and MTX, we examined the impact of decreased and increased MTHFR expression on MTX response in mice.",
"Mthfr-deficient (Mthfr and Mthfr) and wild-type (Mthfr) mice were injected with MTX or saline and assessed for hematological parameters (hematocrit, hemoglobin, red, and white blood cell numbers), plasma homocysteine, nephrotoxicity, hepatotoxicity, and splenic 2'-deoxyuridine 5'-triphosphate/2'-deoxythymidine 5'-triphosphate ratios. MTHFR-overexpressing transgenic mice (MTHFR-Tg) were generated, metabolites and folate distributions were measured, and response to MTX was assessed.",
"MTX-treated Mthfr and Mthfr mice displayed hyperhomocysteinemia and decreased hematocrit, hemoglobin, and red blood cell numbers compared with wild-type animals. Mthfr mice also showed increased nephrotoxicity and hepatotoxicity. MTHFR-Tg mice were generated and confirmed to have increased levels of MTHFR with altered distributions of folate and thiols in a tissue-specific manner. After MTX treatment, MTHFR-Tg mice exhibited the same decreases in hematological parameters as Mthfr-deficient mice, and significantly decreased thymidine synthesis (higher 2'-deoxyuridine 5'-triphosphate/2'-deoxythymidine 5'-triphosphate ratios) compared with wild-type mice, but they were protected from MTX-induced hyperhomocysteinemia."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Cells, Cultured",
"Female",
"Gene Expression",
"Homocysteine",
"Immunosuppression",
"Immunosuppressive Agents",
"Kidney Diseases",
"Male",
"Methotrexate",
"Methylenetetrahydrofolate Reductase (NADPH2)",
"Mice",
"Mice, Inbred BALB C",
"Mice, Inbred C57BL",
"Mice, Knockout",
"Models, Biological",
"Polymorphism, Single Nucleotide"
]
} | Underexpression and overexpression of Mthfr/MTHFR increase MTX-induced myelosuppression but have distinct effects on plasma homocysteine and nephrotoxicity. Pharmacogenetic analysis of polymorphisms in folate-dependent enzymes may be useful in optimization of MTX therapy. | yes | [
{
"from": "human",
"value": "Question: Does altered expression of methylenetetrahydrofolate reductase modify response to methotrexate in mice?\nContext: {'contexts': ['Folates provide one-carbon units for nucleotide synthesis and methylation reactions. A common polymorphism (677C-->T) in methylenetetrahydrofolate reductase (MTHFR) encodes an enzyme with reduced activity. Response to the antifolate methotrexate (MTX) may be modified in 677TT individuals because MTHFR converts nonmethylated folates, used for thymidine and purine synthesis, to 5-methyltetrahydrofolate, used in homocysteine remethylation to methionine. To study potential interactions between MTHFR activity and MTX, we examined the impact of decreased and increased MTHFR expression on MTX response in mice.', \"Mthfr-deficient (Mthfr and Mthfr) and wild-type (Mthfr) mice were injected with MTX or saline and assessed for hematological parameters (hematocrit, hemoglobin, red, and white blood cell numbers), plasma homocysteine, nephrotoxicity, hepatotoxicity, and splenic 2'-deoxyuridine 5'-triphosphate/2'-deoxythymidine 5'-triphosphate ratios. MTHFR-overexpressing transgenic mice (MTHFR-Tg) were generated, metabolites and folate distributions were measured, and response to MTX was assessed.\", \"MTX-treated Mthfr and Mthfr mice displayed hyperhomocysteinemia and decreased hematocrit, hemoglobin, and red blood cell numbers compared with wild-type animals. Mthfr mice also showed increased nephrotoxicity and hepatotoxicity. MTHFR-Tg mice were generated and confirmed to have increased levels of MTHFR with altered distributions of folate and thiols in a tissue-specific manner. After MTX treatment, MTHFR-Tg mice exhibited the same decreases in hematological parameters as Mthfr-deficient mice, and significantly decreased thymidine synthesis (higher 2'-deoxyuridine 5'-triphosphate/2'-deoxythymidine 5'-triphosphate ratios) compared with wild-type mice, but they were protected from MTX-induced hyperhomocysteinemia.\"], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Cells, Cultured', 'Female', 'Gene Expression', 'Homocysteine', 'Immunosuppression', 'Immunosuppressive Agents', 'Kidney Diseases', 'Male', 'Methotrexate', 'Methylenetetrahydrofolate Reductase (NADPH2)', 'Mice', 'Mice, Inbred BALB C', 'Mice, Inbred C57BL', 'Mice, Knockout', 'Models, Biological', 'Polymorphism, Single Nucleotide']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,559,082 | Does the HIV Tat protein affect processing of ribosomal RNA precursor? | {
"contexts": [
"Inside the cell, the HIV Tat protein is mainly found in the nucleus and nucleolus. The nucleolus, the site of ribosome biogenesis, is a highly organized, non-membrane-bound sub-compartment where proteins with a high affinity for nucleolar components are found. While it is well known that Tat accumulates in the nucleolus via a specific nucleolar targeting sequence, its function in this compartment it still unknown.",
"To clarify the significance of the Tat nucleolar localization, we induced the expression of the protein during oogenesis in Drosophila melanogaster strain transgenic for HIV-tat gene. Here we show that Tat localizes in the nucleoli of Drosophila oocyte nurse cells, where it specifically co-localizes with fibrillarin. Tat expression is accompanied by a significant decrease of cytoplasmic ribosomes, which is apparently related to an impairment of ribosomal rRNA precursor processing. Such an event is accounted for by the interaction of Tat with fibrillarin and U3 snoRNA, which are both required for pre-rRNA maturation."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Animals",
"Animals, Genetically Modified",
"Cell Nucleolus",
"Chromosomal Proteins, Non-Histone",
"Drosophila melanogaster",
"Female",
"HIV-1",
"Humans",
"RNA Precursors",
"RNA Processing, Post-Transcriptional",
"RNA, Ribosomal",
"RNA, Small Nucleolar",
"Ribosomes",
"tat Gene Products, Human Immunodeficiency Virus"
]
} | Our data contribute to understanding the function of Tat in the nucleolus, where ribosomal RNA synthesis and cell cycle control take place. The impairment of nucleolar pre-rRNA maturation through the interaction of Tat with fibrillarin-U3snoRNA complex suggests a process by which the virus modulates host response, thus contributing to apoptosis and protein shut-off in HIV-uninfected cells. | yes | [
{
"from": "human",
"value": "Question: Does the HIV Tat protein affect processing of ribosomal RNA precursor?\nContext: {'contexts': ['Inside the cell, the HIV Tat protein is mainly found in the nucleus and nucleolus. The nucleolus, the site of ribosome biogenesis, is a highly organized, non-membrane-bound sub-compartment where proteins with a high affinity for nucleolar components are found. While it is well known that Tat accumulates in the nucleolus via a specific nucleolar targeting sequence, its function in this compartment it still unknown.', 'To clarify the significance of the Tat nucleolar localization, we induced the expression of the protein during oogenesis in Drosophila melanogaster strain transgenic for HIV-tat gene. Here we show that Tat localizes in the nucleoli of Drosophila oocyte nurse cells, where it specifically co-localizes with fibrillarin. Tat expression is accompanied by a significant decrease of cytoplasmic ribosomes, which is apparently related to an impairment of ribosomal rRNA precursor processing. Such an event is accounted for by the interaction of Tat with fibrillarin and U3 snoRNA, which are both required for pre-rRNA maturation.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Animals', 'Animals, Genetically Modified', 'Cell Nucleolus', 'Chromosomal Proteins, Non-Histone', 'Drosophila melanogaster', 'Female', 'HIV-1', 'Humans', 'RNA Precursors', 'RNA Processing, Post-Transcriptional', 'RNA, Ribosomal', 'RNA, Small Nucleolar', 'Ribosomes', 'tat Gene Products, Human Immunodeficiency Virus']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,558,398 | Are nondiagnostic thyroid fine-needle aspiration biopsies no longer a dilemma? | {
"contexts": [
"Nondiagnostic fine-needle aspiration biopsy (ND-FNAB) of the thyroid leads to unnecessary thyroidectomy. The aims of this study were as follows: (1) to determine the risk of malignancy in ND-FNABs, and (2) to evaluate factors that may identify patients at risk for a ND-FNAB.",
"A total of 241 patients who underwent FNAB and thyroidectomy were evaluated for factors associated with a ND-FNAB.",
"A total of 215 women and 26 men underwent FNAB and thyroidectomy. ND-FNAs occurred in 51 of 241 (21%) patients. Ultrasound guidance did not reduce the likelihood of a ND biopsy. Patients with nodules greater than 3 cm had more ND-FNAs. Twenty-one of 51 with a ND biopsy underwent a repeat FNAB. Repeat FNAB was ND in 29% of patients. There was malignant disease in 7 of 51 (14%) with a ND-FNAB. Patient age, sex, thyroid function, gland size, multiple nodules, and final pathology were not related to a ND-FNAB (P > .05)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Biopsy, Fine-Needle",
"Female",
"Humans",
"Male",
"Middle Aged",
"Thyroid Gland",
"Thyroid Nodule",
"Thyroidectomy"
]
} | Most patients with a ND-FNAB have benign disease and low-risk patients with a ND-FNAB on repeat FNA warrant a more conservative approach. | yes | [
{
"from": "human",
"value": "Question: Are nondiagnostic thyroid fine-needle aspiration biopsies no longer a dilemma?\nContext: {'contexts': ['Nondiagnostic fine-needle aspiration biopsy (ND-FNAB) of the thyroid leads to unnecessary thyroidectomy. The aims of this study were as follows: (1) to determine the risk of malignancy in ND-FNABs, and (2) to evaluate factors that may identify patients at risk for a ND-FNAB.', 'A total of 241 patients who underwent FNAB and thyroidectomy were evaluated for factors associated with a ND-FNAB.', 'A total of 215 women and 26 men underwent FNAB and thyroidectomy. ND-FNAs occurred in 51 of 241 (21%) patients. Ultrasound guidance did not reduce the likelihood of a ND biopsy. Patients with nodules greater than 3 cm had more ND-FNAs. Twenty-one of 51 with a ND biopsy underwent a repeat FNAB. Repeat FNAB was ND in 29% of patients. There was malignant disease in 7 of 51 (14%) with a ND-FNAB. Patient age, sex, thyroid function, gland size, multiple nodules, and final pathology were not related to a ND-FNAB (P > .05).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Biopsy, Fine-Needle', 'Female', 'Humans', 'Male', 'Middle Aged', 'Thyroid Gland', 'Thyroid Nodule', 'Thyroidectomy']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,565,283 | Does lentiviral vector-mediated siRNA knockdown of SR-PSOX inhibit foam cell formation in vitro? | {
"contexts": [
"To investigate the expression of scavenger receptor that binds phosphatidylserine and oxidized lipoprotein (SR-PSOX)/CXC chemokine ligand 16 (CXCL16) in the human monocyte-derived cell line THP-1, and the effect of lentiviral vectors for the stable delivery of SR-PSOX/CXCL16 short hairpin RNA on foam cell formation.",
"A lentiviral expression vector containing enhanced green fluorescence protein (GFP) and SR-PSOX small interfering RNA (siRNA) (Lenti-SR-PSOXsi), or the control siRNA (Lenti-NC) gene was constructed. A human monocyte-derived cell line THP-1 was transfected with a different multiplicity of infection (MOI) of Lenti-SR-PSOXsi or Lenti-NC, and cultured to obtain stably-transfected THP- 1KD and THP-1NC cells. After incubation with oxidatively-modified, low-density lipoprotein (Ox-LDL), the expression of SR-PSOX/CXCL16 mRNA was determined by real-time PCR. The expression of the SR-PSOX/CXCL16 protein was detected by flow cytometry analysis. The effect of Lenti-SR-PSOXsi on foam cell formation was assessed by Oil red O-stain analysis.",
"Ox-LDL increased the expression of SR-PSOX/CXCL16 mRNA in a time- and dose-dependent manner in THP-1 cells. Four days after transfection with Lenti-SR-PSOXsi (MOI: 100), the percentage of GFP expression cells was over 89.3%. The expression of the SR-PSOX/ CXCL16 mRNA and protein in THP-1KD cells significantly decreased compared with the parent cells, even the THP-1KD cells stimulated with 40 mg/L Ox-LDL. Ox-LDL uptake experiments in THP-1- and THP-1KD-derived macrophages indicated that SR-PSOX/CXCL16 deficiency decreased the development of macrophage- derived foam cell formation."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Cell Line",
"Cell Survival",
"Chemokine CXCL16",
"Chemokines, CXC",
"Cholesterol, LDL",
"Dose-Response Relationship, Drug",
"Foam Cells",
"Genetic Vectors",
"Humans",
"Lentivirus",
"Monocytes",
"RNA, Messenger",
"RNA, Small Interfering",
"Receptors, Scavenger",
"Reverse Transcriptase Polymerase Chain Reaction",
"Transduction, Genetic"
]
} | The above data showed that SRPSOX siRNA delivered by using lentiviral vectors in THP-1 cells was a powerful tool for studying the effect of SR-PSOX, and decreased the expression of the SRPSOX gene by inhibiting macrophage-derived foam cell formation. | yes | [
{
"from": "human",
"value": "Question: Does lentiviral vector-mediated siRNA knockdown of SR-PSOX inhibit foam cell formation in vitro?\nContext: {'contexts': ['To investigate the expression of scavenger receptor that binds phosphatidylserine and oxidized lipoprotein (SR-PSOX)/CXC chemokine ligand 16 (CXCL16) in the human monocyte-derived cell line THP-1, and the effect of lentiviral vectors for the stable delivery of SR-PSOX/CXCL16 short hairpin RNA on foam cell formation.', 'A lentiviral expression vector containing enhanced green fluorescence protein (GFP) and SR-PSOX small interfering RNA (siRNA) (Lenti-SR-PSOXsi), or the control siRNA (Lenti-NC) gene was constructed. A human monocyte-derived cell line THP-1 was transfected with a different multiplicity of infection (MOI) of Lenti-SR-PSOXsi or Lenti-NC, and cultured to obtain stably-transfected THP- 1KD and THP-1NC cells. After incubation with oxidatively-modified, low-density lipoprotein (Ox-LDL), the expression of SR-PSOX/CXCL16 mRNA was determined by real-time PCR. The expression of the SR-PSOX/CXCL16 protein was detected by flow cytometry analysis. The effect of Lenti-SR-PSOXsi on foam cell formation was assessed by Oil red O-stain analysis.', 'Ox-LDL increased the expression of SR-PSOX/CXCL16 mRNA in a time- and dose-dependent manner in THP-1 cells. Four days after transfection with Lenti-SR-PSOXsi (MOI: 100), the percentage of GFP expression cells was over 89.3%. The expression of the SR-PSOX/ CXCL16 mRNA and protein in THP-1KD cells significantly decreased compared with the parent cells, even the THP-1KD cells stimulated with 40 mg/L Ox-LDL. Ox-LDL uptake experiments in THP-1- and THP-1KD-derived macrophages indicated that SR-PSOX/CXCL16 deficiency decreased the development of macrophage- derived foam cell formation.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Cell Line', 'Cell Survival', 'Chemokine CXCL16', 'Chemokines, CXC', 'Cholesterol, LDL', 'Dose-Response Relationship, Drug', 'Foam Cells', 'Genetic Vectors', 'Humans', 'Lentivirus', 'Monocytes', 'RNA, Messenger', 'RNA, Small Interfering', 'Receptors, Scavenger', 'Reverse Transcriptase Polymerase Chain Reaction', 'Transduction, Genetic']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,565,281 | Does chronic angiotensin ( 1-7 ) injection accelerate STZ-induced diabetic renal injury? | {
"contexts": [
"The renin-angiotensin system (RAS) plays a critical role in blood pressure control and body fluid and electrolyte homeostasis. In the past few years, angiotensin (Ang) (1-7) has been reported to counteract the effects of Ang II and was even considered as a new therapeutical target in RAS. The present study aimed to investigate the effect of Ang (1-7) administration on a diabetic animal model and the modulation on local RAS.",
"Streptozotocin (STZ) injection-induced diabetic rats were used in the experiment. The animals were divided into 3 groups: (1) control; (2) STZ-induced diabetes; and (3) STZ-induced diabetes with chronic Ang (1-7) treatment [D+Ang(1-7)]. In the D+Ang(1-7) group, a dose of 25 microg x kg(-1) x h(-1) of Ang (1-7) was continually injected through the jugular vein by embedding miniosmotic pump for 6 weeks. Plasma glucose, ratio of kidney to body weight, and 24 h urine protein and serum creatinine were monitored by conventional measurement. Plasma and renal Ang II levels were measured by radioimmunoassay. Ang-converting enzyme (ACE), ACE2, Ang II type 1 (AT1) receptor, Ang II type 2 (AT2) receptor, Ang (1-7) Mas receptor, and TGF- beta1 mRNA levels were measured by real time PCR; ACE, ACE2, and TGF- beta1 protein levels were analyzed by Western blotting.",
"The renal function of diabetic rats was significantly retrogressed when compared with that of control rats. After the treatment by constant Ang (1-7) vein injection for 6 weeks, renal function was found to be even worse than diabetic rats, and both TGF-beta1 mRNA and protein levels were elevated in the D+Ang(1-7) group compared with the diabetic rats. The real-time PCR result also showed an increase in ACE mRNA expression and decrease in ACE2 mRNA level in the D+Ang(1-7) group when compared with diabetic rats. The number of AT1 receptors increased in the Ang (1-7)-injected group, while the number of AT2 and Mas receptors decreased."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Angiotensin I",
"Animals",
"DNA, Complementary",
"Diabetes Mellitus, Experimental",
"Diabetic Neuropathies",
"Male",
"Peptide Fragments",
"RNA",
"Rats",
"Rats, Sprague-Dawley",
"Renin-Angiotensin System",
"Reverse Transcriptase Polymerase Chain Reaction"
]
} | Exogenous Ang (1-7) injection did not ameliorate STZinduced diabetic rat renal injury; on the contrary, it accelerated the progressive diabetic nephropathies. | yes | [
{
"from": "human",
"value": "Question: Does chronic angiotensin ( 1-7 ) injection accelerate STZ-induced diabetic renal injury?\nContext: {'contexts': ['The renin-angiotensin system (RAS) plays a critical role in blood pressure control and body fluid and electrolyte homeostasis. In the past few years, angiotensin (Ang) (1-7) has been reported to counteract the effects of Ang II and was even considered as a new therapeutical target in RAS. The present study aimed to investigate the effect of Ang (1-7) administration on a diabetic animal model and the modulation on local RAS.', 'Streptozotocin (STZ) injection-induced diabetic rats were used in the experiment. The animals were divided into 3 groups: (1) control; (2) STZ-induced diabetes; and (3) STZ-induced diabetes with chronic Ang (1-7) treatment [D+Ang(1-7)]. In the D+Ang(1-7) group, a dose of 25 microg x kg(-1) x h(-1) of Ang (1-7) was continually injected through the jugular vein by embedding miniosmotic pump for 6 weeks. Plasma glucose, ratio of kidney to body weight, and 24 h urine protein and serum creatinine were monitored by conventional measurement. Plasma and renal Ang II levels were measured by radioimmunoassay. Ang-converting enzyme (ACE), ACE2, Ang II type 1 (AT1) receptor, Ang II type 2 (AT2) receptor, Ang (1-7) Mas receptor, and TGF- beta1 mRNA levels were measured by real time PCR; ACE, ACE2, and TGF- beta1 protein levels were analyzed by Western blotting.', 'The renal function of diabetic rats was significantly retrogressed when compared with that of control rats. After the treatment by constant Ang (1-7) vein injection for 6 weeks, renal function was found to be even worse than diabetic rats, and both TGF-beta1 mRNA and protein levels were elevated in the D+Ang(1-7) group compared with the diabetic rats. The real-time PCR result also showed an increase in ACE mRNA expression and decrease in ACE2 mRNA level in the D+Ang(1-7) group when compared with diabetic rats. The number of AT1 receptors increased in the Ang (1-7)-injected group, while the number of AT2 and Mas receptors decreased.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Angiotensin I', 'Animals', 'DNA, Complementary', 'Diabetes Mellitus, Experimental', 'Diabetic Neuropathies', 'Male', 'Peptide Fragments', 'RNA', 'Rats', 'Rats, Sprague-Dawley', 'Renin-Angiotensin System', 'Reverse Transcriptase Polymerase Chain Reaction']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,565,287 | Do natural jasmonates of different structures suppress the growth of human neuroblastoma cell line SH-SY5Y and its mechanisms? | {
"contexts": [
"Recent evidence has indicated that members of natural jasmonates, a family of plant stress hormones, exhibit anticancer activity. The current study was undertaken to investigate the effects of jasmonates on the in vitro growth of human neuroblastomas, one of the most common solid tumors in children.",
"Cellular proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide colorimetry and colony formation assay. Apoptosis was detected by Hoechst 33258 staining and flow cytometry. Western blotting was applied to assay gene expression.",
"The administration of natural jasmonates, methyl jasmonate, cis-jasmone, and jasmonic acid to cultured neuroblastoma cell line SH-SY5Y, resulted in a decrease of cell proliferation in a doseand time-dependent manner. However, the in vitro growth of cultured human embryonic kidney (HEK) cell line HEK 293 was not affected by jasmonates. The cell cycles of jasmonate-treated SH-SY5Y cells were arrested at the G2/M phase. The incubation of SH-SY5Y cells with jasmonates resulted in characteristic changes of apoptosis. The anticancer activities of natural jasmonates on SH-SY5Y cells are as follows: methyl jasmonate>cis-jasmone>jasmonic acid. In addition, the expressions of proliferating cell nuclear antigen and N-myc were downregulated by methyl jasmonate. Moreover, methyl jasmonate decreased the expression of the Xlinked inhibitor of apoptosis protein and survivin, critical members of inhibitors of the apoptosis protein family, in SH-SY5Y cells."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Antineoplastic Agents, Phytogenic",
"Apoptosis",
"Cell Cycle",
"Cell Line, Tumor",
"Cell Proliferation",
"Cyclopentanes",
"Humans",
"Inhibitor of Apoptosis Proteins",
"Jasminum",
"Mice",
"Mice, Inbred C57BL",
"Microtubule-Associated Proteins",
"Oxylipins",
"Proliferating Cell Nuclear Antigen",
"Proto-Oncogene Proteins c-myc",
"Structure-Activity Relationship",
"Survivin",
"Tumor Stem Cell Assay",
"X-Linked Inhibitor of Apoptosis Protein"
]
} | Jasmonates suppress the growth of human neuroblastoma cell line SH-SY5Y via inhibiting cell proliferation and inducing apoptosis, which lays the groundwork for further investigation into the anticancer activities and its mechanisms of natural jasmonates on human neuroblastomas. | yes | [
{
"from": "human",
"value": "Question: Do natural jasmonates of different structures suppress the growth of human neuroblastoma cell line SH-SY5Y and its mechanisms?\nContext: {'contexts': ['Recent evidence has indicated that members of natural jasmonates, a family of plant stress hormones, exhibit anticancer activity. The current study was undertaken to investigate the effects of jasmonates on the in vitro growth of human neuroblastomas, one of the most common solid tumors in children.', 'Cellular proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide colorimetry and colony formation assay. Apoptosis was detected by Hoechst 33258 staining and flow cytometry. Western blotting was applied to assay gene expression.', 'The administration of natural jasmonates, methyl jasmonate, cis-jasmone, and jasmonic acid to cultured neuroblastoma cell line SH-SY5Y, resulted in a decrease of cell proliferation in a doseand time-dependent manner. However, the in vitro growth of cultured human embryonic kidney (HEK) cell line HEK 293 was not affected by jasmonates. The cell cycles of jasmonate-treated SH-SY5Y cells were arrested at the G2/M phase. The incubation of SH-SY5Y cells with jasmonates resulted in characteristic changes of apoptosis. The anticancer activities of natural jasmonates on SH-SY5Y cells are as follows: methyl jasmonate>cis-jasmone>jasmonic acid. In addition, the expressions of proliferating cell nuclear antigen and N-myc were downregulated by methyl jasmonate. Moreover, methyl jasmonate decreased the expression of the Xlinked inhibitor of apoptosis protein and survivin, critical members of inhibitors of the apoptosis protein family, in SH-SY5Y cells.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Antineoplastic Agents, Phytogenic', 'Apoptosis', 'Cell Cycle', 'Cell Line, Tumor', 'Cell Proliferation', 'Cyclopentanes', 'Humans', 'Inhibitor of Apoptosis Proteins', 'Jasminum', 'Mice', 'Mice, Inbred C57BL', 'Microtubule-Associated Proteins', 'Oxylipins', 'Proliferating Cell Nuclear Antigen', 'Proto-Oncogene Proteins c-myc', 'Structure-Activity Relationship', 'Survivin', 'Tumor Stem Cell Assay', 'X-Linked Inhibitor of Apoptosis Protein']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,558,197 | Does donor major histocompatibility complex class I expression determine the outcome of prenatal transplantation? | {
"contexts": [
"The failure of in utero transplantation in immune-competent recipients suggests the existence of a fetal immune barrier. The importance of donor major histocompatibility complex (MHC) class I expression in the induction of prenatal tolerance remains undefined. We hypothesized that donor cell MHC class I expression facilitates engraftment in prenatal allogeneic recipients rather than promoting immune rejection.",
"B6.Ly5.2 (class I(+)) or B6.TAP(-/-) (class I(-)) murine fetal liver cells were transplanted into age-matched allogeneic fetal recipients. Survival to weaning and subsequent growth was assessed. Engraftment rates and peripheral blood chimerism levels were measured serially.",
"The presence or absence of class I expression did not affect survival or growth of recipients and no graft-vs-host disease developed. Allogeneic recipients of B6.Ly5.2 cells exhibited significantly higher levels of donor hematopoietic chimerism when compared to recipients of B6.TAP(-/-) cells (27% + 10% vs 11% + 8%; P = .004) that deteriorated further over time."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Disease Models, Animal",
"Female",
"Fetal Tissue Transplantation",
"Graft Rejection",
"Graft Survival",
"Histocompatibility Antigens Class I",
"Liver",
"Liver Transplantation",
"Major Histocompatibility Complex",
"Mice",
"Mice, Inbred BALB C",
"Mice, Inbred C57BL",
"Mice, Inbred Strains",
"Pregnancy",
"Pregnancy, Animal",
"Probability",
"Random Allocation",
"Sensitivity and Specificity",
"Tissue Donors",
"Transplantation Chimera",
"Transplantation Immunology",
"Transplantation, Homologous"
]
} | Donor class I MHC antigen expression is essential for stable long-term engraftment and maintenance of donor-specific tolerance. Further studies are needed to better characterize the role of the fetal innate immune system in prenatal allotransplantation. | yes | [
{
"from": "human",
"value": "Question: Does donor major histocompatibility complex class I expression determine the outcome of prenatal transplantation?\nContext: {'contexts': ['The failure of in utero transplantation in immune-competent recipients suggests the existence of a fetal immune barrier. The importance of donor major histocompatibility complex (MHC) class I expression in the induction of prenatal tolerance remains undefined. We hypothesized that donor cell MHC class I expression facilitates engraftment in prenatal allogeneic recipients rather than promoting immune rejection.', 'B6.Ly5.2 (class I(+)) or B6.TAP(-/-) (class I(-)) murine fetal liver cells were transplanted into age-matched allogeneic fetal recipients. Survival to weaning and subsequent growth was assessed. Engraftment rates and peripheral blood chimerism levels were measured serially.', 'The presence or absence of class I expression did not affect survival or growth of recipients and no graft-vs-host disease developed. Allogeneic recipients of B6.Ly5.2 cells exhibited significantly higher levels of donor hematopoietic chimerism when compared to recipients of B6.TAP(-/-) cells (27% + 10% vs 11% + 8%; P = .004) that deteriorated further over time.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Disease Models, Animal', 'Female', 'Fetal Tissue Transplantation', 'Graft Rejection', 'Graft Survival', 'Histocompatibility Antigens Class I', 'Liver', 'Liver Transplantation', 'Major Histocompatibility Complex', 'Mice', 'Mice, Inbred BALB C', 'Mice, Inbred C57BL', 'Mice, Inbred Strains', 'Pregnancy', 'Pregnancy, Animal', 'Probability', 'Random Allocation', 'Sensitivity and Specificity', 'Tissue Donors', 'Transplantation Chimera', 'Transplantation Immunology', 'Transplantation, Homologous']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,573,120 | Does postoperative PTH measurement facilitate day 1 discharge after total thyroidectomy? | {
"contexts": [
"A new protocol for postoperative calcium management was developed with the aim of achieving an increase in the proportion of patients being safely discharged on the first postoperative day. We present our experience with the first 50 patients treated under this new protocol.",
"A cohort study was performed involving the first 50 patients admitted for total or completion thyroidectomy, those data were then compared with a control group. Intact PTH (iPTH) was measured at 4-h postoperatively and patients with iPTH in the normal range were discharged on the first postoperative day.",
"Mean age and sex distribution were similar in both groups. Mean lowest postoperative corrected calcium levels in the study group were 2.19 mmol/l and 2.15 mmol/l in the control group (P = 0.24). Parathyroid auto-transplantation was associated with low PTH levels (risk ratio = 0.49). Over 50% of patients (n = 27) were successfully discharged on the first postoperative day in the study group and no patient required readmission. Length of stay was significantly shorter in the study group, mean 1.64 vs. 2.20 days (P < 0.05)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Calcium",
"Cohort Studies",
"Female",
"Humans",
"Hypocalcemia",
"Immunoassay",
"Length of Stay",
"Male",
"Middle Aged",
"Parathyroid Hormone",
"Patient Discharge",
"Postoperative Period",
"Predictive Value of Tests",
"Thyroidectomy",
"Time Factors"
]
} | The use of iPTH accurately predicts hypocalcaemia after total thyroidectomy and can be used to facilitate safe early discharge for patients. | yes | [
{
"from": "human",
"value": "Question: Does postoperative PTH measurement facilitate day 1 discharge after total thyroidectomy?\nContext: {'contexts': ['A new protocol for postoperative calcium management was developed with the aim of achieving an increase in the proportion of patients being safely discharged on the first postoperative day. We present our experience with the first 50 patients treated under this new protocol.', 'A cohort study was performed involving the first 50 patients admitted for total or completion thyroidectomy, those data were then compared with a control group. Intact PTH (iPTH) was measured at 4-h postoperatively and patients with iPTH in the normal range were discharged on the first postoperative day.', 'Mean age and sex distribution were similar in both groups. Mean lowest postoperative corrected calcium levels in the study group were 2.19 mmol/l and 2.15 mmol/l in the control group (P = 0.24). Parathyroid auto-transplantation was associated with low PTH levels (risk ratio = 0.49). Over 50% of patients (n = 27) were successfully discharged on the first postoperative day in the study group and no patient required readmission. Length of stay was significantly shorter in the study group, mean 1.64 vs. 2.20 days (P < 0.05).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Calcium', 'Cohort Studies', 'Female', 'Humans', 'Hypocalcemia', 'Immunoassay', 'Length of Stay', 'Male', 'Middle Aged', 'Parathyroid Hormone', 'Patient Discharge', 'Postoperative Period', 'Predictive Value of Tests', 'Thyroidectomy', 'Time Factors']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,550,262 | Do mouse neutrophils lacking lamin B-receptor expression exhibit aberrant development and lack critical functional responses? | {
"contexts": [
"The capacity of neutrophils to eradicate bacterial infections is dependent on normal development and activation of functional responses, which include chemotaxis and generation of oxygen radicals during the respiratory burst. A unique feature of the neutrophil is its highly lobulated nucleus, which is thought to facilitate chemotaxis, but may also play a role in other critical neutrophil functions. Nuclear lobulation is dependent on expression of the inner nuclear envelope protein, the lamin B receptor (LBR), mutations of which cause hypolobulated neutrophil nuclei in human Pelger-Huët anomaly and the \"ichthyosis\" (ic) phenotype in mice. In this study, we have investigated roles for LBR in mediating neutrophil development and activation of multiple neutrophil functions, including chemotaxis and the respiratory burst.",
"A progenitor EML cell line was generated from an ic/ic mouse, and derived cells that lacked LBR expression were induced to mature neutrophils and then examined for abnormal morphology and functional responses.",
"Neutrophils derived from EML-ic/ic cells exhibited nuclear hypolobulation identical to that observed in ichthyosis mice. The ic/ic neutrophils also displayed abnormal chemotaxis, supporting the notion that nuclear segmentation augments neutrophil extravasation. Furthermore, promyelocytic forms of ic/ic cells displayed decreased proliferative responses and produced a deficient respiratory burst upon terminal maturation."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Cell Differentiation",
"Cell Line",
"Cell Nucleus Shape",
"Chemotaxis",
"Female",
"Gene Deletion",
"Ichthyosis",
"Male",
"Mice",
"Mice, Inbred C57BL",
"Neutrophils",
"Receptors, Cytoplasmic and Nuclear",
"Receptors, Immunologic",
"Respiratory Burst"
]
} | Our studies of promyelocytes that lack LBR expression have identified roles for LBR in regulating not only the morphologic maturation of the neutrophil nucleus, but also proliferative and functional responses that are critical to innate immunity. | yes | [
{
"from": "human",
"value": "Question: Do mouse neutrophils lacking lamin B-receptor expression exhibit aberrant development and lack critical functional responses?\nContext: {'contexts': ['The capacity of neutrophils to eradicate bacterial infections is dependent on normal development and activation of functional responses, which include chemotaxis and generation of oxygen radicals during the respiratory burst. A unique feature of the neutrophil is its highly lobulated nucleus, which is thought to facilitate chemotaxis, but may also play a role in other critical neutrophil functions. Nuclear lobulation is dependent on expression of the inner nuclear envelope protein, the lamin B receptor (LBR), mutations of which cause hypolobulated neutrophil nuclei in human Pelger-Huët anomaly and the \"ichthyosis\" (ic) phenotype in mice. In this study, we have investigated roles for LBR in mediating neutrophil development and activation of multiple neutrophil functions, including chemotaxis and the respiratory burst.', 'A progenitor EML cell line was generated from an ic/ic mouse, and derived cells that lacked LBR expression were induced to mature neutrophils and then examined for abnormal morphology and functional responses.', 'Neutrophils derived from EML-ic/ic cells exhibited nuclear hypolobulation identical to that observed in ichthyosis mice. The ic/ic neutrophils also displayed abnormal chemotaxis, supporting the notion that nuclear segmentation augments neutrophil extravasation. Furthermore, promyelocytic forms of ic/ic cells displayed decreased proliferative responses and produced a deficient respiratory burst upon terminal maturation.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Cell Differentiation', 'Cell Line', 'Cell Nucleus Shape', 'Chemotaxis', 'Female', 'Gene Deletion', 'Ichthyosis', 'Male', 'Mice', 'Mice, Inbred C57BL', 'Neutrophils', 'Receptors, Cytoplasmic and Nuclear', 'Receptors, Immunologic', 'Respiratory Burst']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,565,828 | Does genetic variability in progranulin contribute to risk for clinically diagnosed Alzheimer disease? | {
"contexts": [
"Loss-of-function mutations in the progranulin gene (PGRN) were identified in frontotemporal lobar degeneration (FTLD) with ubiquitin-immunoreactive neuronal inclusions (FTLD-U). We assessed whether PGRN also contributes to genetic risk for Alzheimer disease (AD) in an extended Belgian AD patient group (n = 779, onset age 74.7 +/- 8.7 years).",
"A mutation analysis of the PGRN coding region was performed. The effect of missense mutations was assessed using in silico predictions and protein modeling. Risk effects of common genetic variants were estimated by logistic regression analysis and gene-based haplotype association analysis.",
"We observed seven missense mutations in eight patients (1.3%). Convincing pathogenic evidence was obtained for two missense mutations, p.Cys139Arg and p.Pro451Leu, affecting PGRN protein folding and leading to loss of PGRN by degradation of the misfolded protein. In addition, we showed that PGRN haplotypes were associated with increased risk for AD."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Aged, 80 and over",
"Alzheimer Disease",
"Amino Acid Sequence",
"DNA Mutational Analysis",
"Female",
"Genetic Markers",
"Genetic Predisposition to Disease",
"Genetic Testing",
"Genetic Variation",
"Haplotypes",
"Humans",
"Intercellular Signaling Peptides and Proteins",
"Male",
"Middle Aged",
"Mutation, Missense",
"Progranulins",
"Protein Folding"
]
} | Our data support a role for PGRN in patients with clinically diagnosed Alzheimer disease (AD). Further, we hypothesize that at least some PGRN missense mutations might lead to loss of functional protein. Whether the underlying pathology in our cases proves to be AD, frontotemporal lobar degeneration, or a combination of the two must await further investigations. | yes | [
{
"from": "human",
"value": "Question: Does genetic variability in progranulin contribute to risk for clinically diagnosed Alzheimer disease?\nContext: {'contexts': ['Loss-of-function mutations in the progranulin gene (PGRN) were identified in frontotemporal lobar degeneration (FTLD) with ubiquitin-immunoreactive neuronal inclusions (FTLD-U). We assessed whether PGRN also contributes to genetic risk for Alzheimer disease (AD) in an extended Belgian AD patient group (n = 779, onset age 74.7 +/- 8.7 years).', 'A mutation analysis of the PGRN coding region was performed. The effect of missense mutations was assessed using in silico predictions and protein modeling. Risk effects of common genetic variants were estimated by logistic regression analysis and gene-based haplotype association analysis.', 'We observed seven missense mutations in eight patients (1.3%). Convincing pathogenic evidence was obtained for two missense mutations, p.Cys139Arg and p.Pro451Leu, affecting PGRN protein folding and leading to loss of PGRN by degradation of the misfolded protein. In addition, we showed that PGRN haplotypes were associated with increased risk for AD.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Aged, 80 and over', 'Alzheimer Disease', 'Amino Acid Sequence', 'DNA Mutational Analysis', 'Female', 'Genetic Markers', 'Genetic Predisposition to Disease', 'Genetic Testing', 'Genetic Variation', 'Haplotypes', 'Humans', 'Intercellular Signaling Peptides and Proteins', 'Male', 'Middle Aged', 'Mutation, Missense', 'Progranulins', 'Protein Folding']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,560,542 | Do perinatal androgens and adult behavior vary with nestling social system in siblicidal boobies? | {
"contexts": [
"Exposure to androgens early in development, while activating adaptive aggressive behavior, may also exert long-lasting effects on non-target components of phenotype. Here we compare these organizational effects of perinatal androgens in closely related Nazca (Sula granti) and blue-footed (S. nebouxii) boobies that differ in neonatal social system. The older of two Nazca booby hatchlings unconditionally attacks and ejects the younger from the nest within days of hatching, while blue-footed booby neonates lack lethal aggression. Both Nazca booby chicks facultatively upregulate testosterone (T) during fights, motivating the prediction that baseline androgen levels differ between obligately siblicidal and other species.",
"We show that obligately siblicidal Nazca boobies hatch with higher circulating androgen levels than do facultatively siblicidal blue-footed boobies, providing comparative evidence of the role of androgens in sociality. Although androgens confer a short-term benefit of increased aggression to Nazca booby neonates, exposure to elevated androgen levels during this sensitive period in development can also induce long-term organizational effects on behavior or morphology. Adult Nazca boobies show evidence of organizational effects of early androgen exposure in aberrant adult behavior: they visit unattended non-familial chicks in the colony and direct mixtures of aggression, affiliative, and sexual behavior toward them. In a longitudinal analysis, we found that the most active Non-parental Adult Visitors (NAVs) were those with a history of siblicidal behavior as a neonate, suggesting that the tendency to show social interest in chicks is programmed, in part, by the high perinatal androgens associated with obligate siblicide. Data from closely related blue-footed boobies provide comparative support for this interpretation. Lacking obligate siblicide, they hatch with a corresponding low androgen level, and blue-footed booby adults show a much lower frequency of NAV behavior and a lower probability of behaving aggressively during NAV interactions. This species difference in adult social behavior appears to have roots in both pleiotropic and experiential effects of nestling social system."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Androgens",
"Animals",
"Behavior, Animal",
"Birds",
"Female"
]
} | Our results indicate that Nazca boobies experience life-long consequences of androgenic preparation for an early battle to the death. | yes | [
{
"from": "human",
"value": "Question: Do perinatal androgens and adult behavior vary with nestling social system in siblicidal boobies?\nContext: {'contexts': ['Exposure to androgens early in development, while activating adaptive aggressive behavior, may also exert long-lasting effects on non-target components of phenotype. Here we compare these organizational effects of perinatal androgens in closely related Nazca (Sula granti) and blue-footed (S. nebouxii) boobies that differ in neonatal social system. The older of two Nazca booby hatchlings unconditionally attacks and ejects the younger from the nest within days of hatching, while blue-footed booby neonates lack lethal aggression. Both Nazca booby chicks facultatively upregulate testosterone (T) during fights, motivating the prediction that baseline androgen levels differ between obligately siblicidal and other species.', 'We show that obligately siblicidal Nazca boobies hatch with higher circulating androgen levels than do facultatively siblicidal blue-footed boobies, providing comparative evidence of the role of androgens in sociality. Although androgens confer a short-term benefit of increased aggression to Nazca booby neonates, exposure to elevated androgen levels during this sensitive period in development can also induce long-term organizational effects on behavior or morphology. Adult Nazca boobies show evidence of organizational effects of early androgen exposure in aberrant adult behavior: they visit unattended non-familial chicks in the colony and direct mixtures of aggression, affiliative, and sexual behavior toward them. In a longitudinal analysis, we found that the most active Non-parental Adult Visitors (NAVs) were those with a history of siblicidal behavior as a neonate, suggesting that the tendency to show social interest in chicks is programmed, in part, by the high perinatal androgens associated with obligate siblicide. Data from closely related blue-footed boobies provide comparative support for this interpretation. Lacking obligate siblicide, they hatch with a corresponding low androgen level, and blue-footed booby adults show a much lower frequency of NAV behavior and a lower probability of behaving aggressively during NAV interactions. This species difference in adult social behavior appears to have roots in both pleiotropic and experiential effects of nestling social system.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Androgens', 'Animals', 'Behavior, Animal', 'Birds', 'Female']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,560,548 | Is free Brick1 a trimeric precursor in the assembly of a functional wave complex? | {
"contexts": [
"The Wave complex activates the Arp2/3 complex, inducing actin polymerization in lamellipodia and membrane ruffles. The Wave complex is composed of five subunits, the smallest of which, Brick1/Hspc300 (Brk1), is the least characterized. We previously reported that, unlike the other subunits, Brk1 also exists as a free form.",
"Here we report that this free form of Brk1 is composed of homotrimers. Using a novel assay in which purified free Brk1 is electroporated into HeLa cells, we were able to follow its biochemical fate in cells and to show that free Brk1 becomes incorporated into the Wave complex. Importantly, incorporation of free Brk1 into the Wave complex was blocked upon inhibition of protein synthesis and incorporated Brk1 was found to associate preferentially with neosynthesized subunits. Brk1 depleted HeLa cells were found to bleb, as were Nap1, Wave2 or ARPC2 depleted cells, suggesting that this blebbing phenotype of Brk1 depleted cells is due to an impairment of the Wave complex function rather than a specific function of free Brk1. Blebs of Brk1 depleted cells were emitted at sites where lamellipodia and membrane ruffles were normally emitted. In Brk1 depleted cells, the electroporation of free Brk1 was sufficient to restore Wave complex assembly and to rescue the blebbing phenotype."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Amino Acid Sequence",
"Biopolymers",
"Cell Line",
"Cytoskeletal Proteins",
"Electrophoresis, Polyacrylamide Gel",
"Electroporation",
"Humans",
"Immunoprecipitation",
"Molecular Sequence Data",
"Transfection"
]
} | Together these results establish that the free form of Brk1 is an essential precursor in the assembly of a functional Wave complex. | yes | [
{
"from": "human",
"value": "Question: Is free Brick1 a trimeric precursor in the assembly of a functional wave complex?\nContext: {'contexts': ['The Wave complex activates the Arp2/3 complex, inducing actin polymerization in lamellipodia and membrane ruffles. The Wave complex is composed of five subunits, the smallest of which, Brick1/Hspc300 (Brk1), is the least characterized. We previously reported that, unlike the other subunits, Brk1 also exists as a free form.', 'Here we report that this free form of Brk1 is composed of homotrimers. Using a novel assay in which purified free Brk1 is electroporated into HeLa cells, we were able to follow its biochemical fate in cells and to show that free Brk1 becomes incorporated into the Wave complex. Importantly, incorporation of free Brk1 into the Wave complex was blocked upon inhibition of protein synthesis and incorporated Brk1 was found to associate preferentially with neosynthesized subunits. Brk1 depleted HeLa cells were found to bleb, as were Nap1, Wave2 or ARPC2 depleted cells, suggesting that this blebbing phenotype of Brk1 depleted cells is due to an impairment of the Wave complex function rather than a specific function of free Brk1. Blebs of Brk1 depleted cells were emitted at sites where lamellipodia and membrane ruffles were normally emitted. In Brk1 depleted cells, the electroporation of free Brk1 was sufficient to restore Wave complex assembly and to rescue the blebbing phenotype.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Amino Acid Sequence', 'Biopolymers', 'Cell Line', 'Cytoskeletal Proteins', 'Electrophoresis, Polyacrylamide Gel', 'Electroporation', 'Humans', 'Immunoprecipitation', 'Molecular Sequence Data', 'Transfection']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,562,166 | Is the Brugada type 1 electrocardiographic pattern common among Filipinos? | {
"contexts": [
"To measure the prevalence of the Brugada type 1 ECG pattern in the general population in the Philippines. STUDY SETTING AND DESIGN: Sudden unexplained death syndrome is rare in the West but is common among Southeast Asians. Ventricular fibrillation is the terminal event. The Brugada type 1 electrocardiographic (ECG) pattern with J point and coved ST elevation in right precordial leads, is a marker for sudden unexplained death syndrome. Its prevalence in the general population is unknown. A cross-sectional nationwide survey was performed in the Philippines in 2003 using a stratified multistage sampling design covering all the regions and provinces in the country. ECGs were performed in all adults surveyed. The prevalences of the Brugada type 1 ECG pattern (coved type) and any type Brugada ECG pattern were determined.",
"The Brugada type 1 (coved) ECG pattern in the general population in the Philippines was found in 0.2% (95% Confidence Interval [CI] 0.03%-0.36%) of the population. Among males the prevalence was 0.3% (+/-0.1). The prevalence of any type Brugada ECG was 2% (95% CI 1.5%-2.6%)."
],
"labels": [
"OBJECTIVE",
"RESULTS"
],
"meshes": [
"Adult",
"Age Distribution",
"Aged",
"Brugada Syndrome",
"Cross-Sectional Studies",
"Electrocardiography",
"Female",
"Humans",
"Male",
"Middle Aged",
"Philippines",
"Prevalence",
"Sex Distribution",
"Signal Processing, Computer-Assisted",
"Young Adult"
]
} | The Brugada ECG pattern is common among Filipinos. There is a need to determine the risk of sudden death among individuals with this marker in the general population. | yes | [
{
"from": "human",
"value": "Question: Is the Brugada type 1 electrocardiographic pattern common among Filipinos?\nContext: {'contexts': ['To measure the prevalence of the Brugada type 1 ECG pattern in the general population in the Philippines. STUDY SETTING AND DESIGN: Sudden unexplained death syndrome is rare in the West but is common among Southeast Asians. Ventricular fibrillation is the terminal event. The Brugada type 1 electrocardiographic (ECG) pattern with J point and coved ST elevation in right precordial leads, is a marker for sudden unexplained death syndrome. Its prevalence in the general population is unknown. A cross-sectional nationwide survey was performed in the Philippines in 2003 using a stratified multistage sampling design covering all the regions and provinces in the country. ECGs were performed in all adults surveyed. The prevalences of the Brugada type 1 ECG pattern (coved type) and any type Brugada ECG pattern were determined.', 'The Brugada type 1 (coved) ECG pattern in the general population in the Philippines was found in 0.2% (95% Confidence Interval [CI] 0.03%-0.36%) of the population. Among males the prevalence was 0.3% (+/-0.1). The prevalence of any type Brugada ECG was 2% (95% CI 1.5%-2.6%).'], 'labels': ['OBJECTIVE', 'RESULTS'], 'meshes': ['Adult', 'Age Distribution', 'Aged', 'Brugada Syndrome', 'Cross-Sectional Studies', 'Electrocardiography', 'Female', 'Humans', 'Male', 'Middle Aged', 'Philippines', 'Prevalence', 'Sex Distribution', 'Signal Processing, Computer-Assisted', 'Young Adult']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,559,744 | Is early laparoscopic cholecystectomy the preferred management of acute cholecystitis? | {
"contexts": [
"Early laparoscopic cholecystectomy (LC) results in a shorter length of stay and acceptable conversion and complication rates when compared with antibiotic therapy plus interval LC or percutaneous cholecystostomy in patients admitted to a surgical service because of acute cholecystitis. However, actual practice does not conform to current evidence.",
"Retrospective cohort study.",
"Urban teaching hospital.",
"Data were abstracted from the medical records of all patients with acute cholecystitis admitted to the surgical service via the emergency department during 36 months (October 1, 2002, to September 30, 2005). Patients were divided into 5 groups on the basis of treatment received. Length of stay, duration of symptoms, major complications, and conversion rates were analyzed.",
"Of 173 patients with acute cholecystitis, 71 (41%) underwent early LC. Of 102 patients treated with antibiotic therapy alone (59%), 57 were discharged; antibiotic therapy was unsuccessful in 45 patients. Of the patients in whom antibiotic therapy was unsuccessful, 26 underwent late LC and 19 underwent percutaneous cholecystostomy. Interval LC was eventually performed in 55 patients who did not undergo surgery during the index admission. Length of stay was significantly shorter in the early LC group compared with the interval LC group (P < .001). Conversion rates were not statistically different for the 3 LC groups (early LC, 5.6%; late LC, 11.5%; and interval LC, 9.1%). The only biliary complication occurred in the interval LC group."
],
"labels": [
"OBJECTIVE",
"METHODS",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Cholecystectomy, Laparoscopic",
"Cholecystitis, Acute",
"Female",
"Follow-Up Studies",
"Humans",
"Incidence",
"Length of Stay",
"Los Angeles",
"Male",
"Middle Aged",
"Postoperative Complications",
"Retrospective Studies",
"Time Factors",
"Treatment Outcome",
"Urban Population"
]
} | Early laparoscopic cholecystectomy resulted in a significantly reduced length of stay, no major complications, and no significant difference in conversion rates when compared with initial antibiotic treatment and interval LC. Despite these advantages, early LC is not the most common treatment for acute cholecystitis in practice. | yes | [
{
"from": "human",
"value": "Question: Is early laparoscopic cholecystectomy the preferred management of acute cholecystitis?\nContext: {'contexts': ['Early laparoscopic cholecystectomy (LC) results in a shorter length of stay and acceptable conversion and complication rates when compared with antibiotic therapy plus interval LC or percutaneous cholecystostomy in patients admitted to a surgical service because of acute cholecystitis. However, actual practice does not conform to current evidence.', 'Retrospective cohort study.', 'Urban teaching hospital.', 'Data were abstracted from the medical records of all patients with acute cholecystitis admitted to the surgical service via the emergency department during 36 months (October 1, 2002, to September 30, 2005). Patients were divided into 5 groups on the basis of treatment received. Length of stay, duration of symptoms, major complications, and conversion rates were analyzed.', 'Of 173 patients with acute cholecystitis, 71 (41%) underwent early LC. Of 102 patients treated with antibiotic therapy alone (59%), 57 were discharged; antibiotic therapy was unsuccessful in 45 patients. Of the patients in whom antibiotic therapy was unsuccessful, 26 underwent late LC and 19 underwent percutaneous cholecystostomy. Interval LC was eventually performed in 55 patients who did not undergo surgery during the index admission. Length of stay was significantly shorter in the early LC group compared with the interval LC group (P < .001). Conversion rates were not statistically different for the 3 LC groups (early LC, 5.6%; late LC, 11.5%; and interval LC, 9.1%). The only biliary complication occurred in the interval LC group.'], 'labels': ['OBJECTIVE', 'METHODS', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Cholecystectomy, Laparoscopic', 'Cholecystitis, Acute', 'Female', 'Follow-Up Studies', 'Humans', 'Incidence', 'Length of Stay', 'Los Angeles', 'Male', 'Middle Aged', 'Postoperative Complications', 'Retrospective Studies', 'Time Factors', 'Treatment Outcome', 'Urban Population']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,547,908 | Are higher plasma myeloperoxidase levels associated with an increased risk for cardiovascular events in HIV-infected adults? | {
"contexts": [
"Elevated myeloperoxidase (MPO) levels are predictive of high cardiovascular (CV) risk in the general population. The value of MPO as a CV marker in the HIV population has not been investigated.",
"Medical records were reviewed to identify HIV+ patients with a documented CV event (myocardial ischemia/infarction) and stored plasma samples within 12 months prior to the event. HIV+ adults with no CV history and with similarly available stored plasma samples were site-, age-, and gender-matched 1:1 to cases.",
"We identified 124 participants (62 case-control pairs): 94% male, median age 46 years. Median (IQR) MPO levels (pmoles/L) were lower in cases vs. controls: 292 (235-376) vs. 320 (249-467); p= .004. Cases were more likely to have other CV risk factors, including smoking, hypertension, and higher cholesterol and triglycerides. The observed MPO directional difference persisted after controlling for CV risk factors. In the reduced model, observed differences in MPO remained independently and negatively associated with CV event (p= .03) after adjusting for two positively associated risk factors, differences in cholesterol levels (p= .01), and differences in smoking history (ever smoked vs. never smoked; p= .04). Differences in triglyceride levels and hypertension were not statistically significant independent risk factors in this sample (p> .05). Within cases, MPO was negatively correlated with CD4 count (rs= -0. 40, p= .0023) and age (rs= -0. 34, p= .01). In contrast, age at blood draw was positively correlated with MPO in controls (rs= 0.28, p= .031) and CD4 was uncorrelated (rs= -0. 01, p> .9). No other factors were significantly correlated with MPO within groups."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Biomarkers",
"Cardiovascular Diseases",
"Case-Control Studies",
"Female",
"HIV Infections",
"Humans",
"Male",
"Middle Aged",
"Peroxidase",
"Risk Factors"
]
} | In contrast to the general population, higher MPO levels were not predictive of CV events in this study, underscoring the fact that pathways operative in HIV arteriopathy may be distinct from traditional CV disease pathogenesis. | no | [
{
"from": "human",
"value": "Question: Are higher plasma myeloperoxidase levels associated with an increased risk for cardiovascular events in HIV-infected adults?\nContext: {'contexts': ['Elevated myeloperoxidase (MPO) levels are predictive of high cardiovascular (CV) risk in the general population. The value of MPO as a CV marker in the HIV population has not been investigated.', 'Medical records were reviewed to identify HIV+ patients with a documented CV event (myocardial ischemia/infarction) and stored plasma samples within 12 months prior to the event. HIV+ adults with no CV history and with similarly available stored plasma samples were site-, age-, and gender-matched 1:1 to cases.', 'We identified 124 participants (62 case-control pairs): 94% male, median age 46 years. Median (IQR) MPO levels (pmoles/L) were lower in cases vs. controls: 292 (235-376) vs. 320 (249-467); p= .004. Cases were more likely to have other CV risk factors, including smoking, hypertension, and higher cholesterol and triglycerides. The observed MPO directional difference persisted after controlling for CV risk factors. In the reduced model, observed differences in MPO remained independently and negatively associated with CV event (p= .03) after adjusting for two positively associated risk factors, differences in cholesterol levels (p= .01), and differences in smoking history (ever smoked vs. never smoked; p= .04). Differences in triglyceride levels and hypertension were not statistically significant independent risk factors in this sample (p> .05). Within cases, MPO was negatively correlated with CD4 count (rs= -0. 40, p= .0023) and age (rs= -0. 34, p= .01). In contrast, age at blood draw was positively correlated with MPO in controls (rs= 0.28, p= .031) and CD4 was uncorrelated (rs= -0. 01, p> .9). No other factors were significantly correlated with MPO within groups.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Biomarkers', 'Cardiovascular Diseases', 'Case-Control Studies', 'Female', 'HIV Infections', 'Humans', 'Male', 'Middle Aged', 'Peroxidase', 'Risk Factors']}"
},
{
"from": "gpt",
"value": "Answer: no"
}
]
|
18,572,351 | Is the antithrombotic effect of dextran-40 in man due to enhanced fibrinolysis in vivo? | {
"contexts": [
"Dextran-40 is effective in reducing postoperative Doppler-detectable embolization in patients undergoing carotid endarterectomy (CEA). Dextrans are thought to have antithrombotic and antiplatelet effects. The mode of action is unclear. In rats, dextran blocks uptake of tissue plasminogen activator (tPA) by mannose-binding receptors. Because this would have the effect of enhancing endogenous fibrinolysis, we explored this effect of dextran-40 on fibrinolysis in man.",
"Twenty patients undergoing endovascular stenting for abdominal aortic aneurysm were randomized to receive 100 mL of 10% dextran-40 or saline, over 1 hour, during their operation in addition to heparin. Blood samples were taken preoperatively, intraoperatively (immediately after operative procedure), and 24 hours postoperatively. Thrombi were formed in a Chandler loop and used to assess endogenous fibrinolysis over 24 hours, measured as the fall in thrombus weight, and the release of fluorescently labelled fibrinogen from the thrombus. Plasma samples were analyzed for markers of fibrinolysis; plasmin-antiplasmin (PAP), PAI-1, and t-PA, and for functional von Willebrand factor (vWF). Platelet response to thrombin and other agonists was measured by flow cytometry.",
"Thrombi formed ex vivo from the intraoperative blood samples from the dextran-treated patients exhibited significantly greater fibrinolysis vs preoperative samples, seen both as a significantly greater percentage reduction in thrombus weight (from 34.7% to 70.6% reduction) and as an 175% increase in the release of fluorescence (P < .05). Fibrinolysis returned to baseline levels the next day. No change was seen in the saline-treated group. Plasma levels of PAP and PAI-1 increased significantly postoperatively in the dextran-treated group vs the saline group (P < .05). The postoperative level of functional VWF was significantly lower in the dextran-treated group vs controls. A specific reduction occurred in the platelet response to thrombin, but not to other agonists, in the intraoperative samples from the dextran-treated group (11.1% vs 37.1%; P = .022), which was not seen in the controls."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Aged, 80 and over",
"Aortic Aneurysm, Abdominal",
"Blood Platelets",
"Dextrans",
"Double-Blind Method",
"Fibrinolysin",
"Fibrinolysis",
"Fibrinolytic Agents",
"Flow Cytometry",
"Humans",
"Infusions, Intra-Arterial",
"Male",
"Plasminogen Activator Inhibitor 1",
"Platelet Activation",
"Prospective Studies",
"Stents",
"Thrombin",
"Thromboembolism",
"Time Factors",
"Tissue Plasminogen Activator",
"Treatment Outcome",
"Vascular Surgical Procedures",
"alpha-2-Antiplasmin",
"von Willebrand Factor"
]
} | These data are consistent with a rise in plasmin due to dextran blockade of tPA uptake in vivo, leading to enhanced fibrinolysis, cleavage of vWF and of the platelet protease-activated receptor-1 (PAR-1) thrombin receptor. This suggests that dextran exerts a combined therapeutic effect, enhancing endogenous fibrinolysis, whilst also reducing platelet adhesion to vWF and platelet activation by thrombin. The proven antithrombotic efficacy of low-dose dextran in carotid surgery may be applicable to wider therapeutic use. | yes | [
{
"from": "human",
"value": "Question: Is the antithrombotic effect of dextran-40 in man due to enhanced fibrinolysis in vivo?\nContext: {'contexts': ['Dextran-40 is effective in reducing postoperative Doppler-detectable embolization in patients undergoing carotid endarterectomy (CEA). Dextrans are thought to have antithrombotic and antiplatelet effects. The mode of action is unclear. In rats, dextran blocks uptake of tissue plasminogen activator (tPA) by mannose-binding receptors. Because this would have the effect of enhancing endogenous fibrinolysis, we explored this effect of dextran-40 on fibrinolysis in man.', 'Twenty patients undergoing endovascular stenting for abdominal aortic aneurysm were randomized to receive 100 mL of 10% dextran-40 or saline, over 1 hour, during their operation in addition to heparin. Blood samples were taken preoperatively, intraoperatively (immediately after operative procedure), and 24 hours postoperatively. Thrombi were formed in a Chandler loop and used to assess endogenous fibrinolysis over 24 hours, measured as the fall in thrombus weight, and the release of fluorescently labelled fibrinogen from the thrombus. Plasma samples were analyzed for markers of fibrinolysis; plasmin-antiplasmin (PAP), PAI-1, and t-PA, and for functional von Willebrand factor (vWF). Platelet response to thrombin and other agonists was measured by flow cytometry.', 'Thrombi formed ex vivo from the intraoperative blood samples from the dextran-treated patients exhibited significantly greater fibrinolysis vs preoperative samples, seen both as a significantly greater percentage reduction in thrombus weight (from 34.7% to 70.6% reduction) and as an 175% increase in the release of fluorescence (P < .05). Fibrinolysis returned to baseline levels the next day. No change was seen in the saline-treated group. Plasma levels of PAP and PAI-1 increased significantly postoperatively in the dextran-treated group vs the saline group (P < .05). The postoperative level of functional VWF was significantly lower in the dextran-treated group vs controls. A specific reduction occurred in the platelet response to thrombin, but not to other agonists, in the intraoperative samples from the dextran-treated group (11.1% vs 37.1%; P = .022), which was not seen in the controls.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Aged, 80 and over', 'Aortic Aneurysm, Abdominal', 'Blood Platelets', 'Dextrans', 'Double-Blind Method', 'Fibrinolysin', 'Fibrinolysis', 'Fibrinolytic Agents', 'Flow Cytometry', 'Humans', 'Infusions, Intra-Arterial', 'Male', 'Plasminogen Activator Inhibitor 1', 'Platelet Activation', 'Prospective Studies', 'Stents', 'Thrombin', 'Thromboembolism', 'Time Factors', 'Tissue Plasminogen Activator', 'Treatment Outcome', 'Vascular Surgical Procedures', 'alpha-2-Antiplasmin', 'von Willebrand Factor']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,573,428 | Does persistent N2 disease after induction therapy jeopardize early and medium term outcomes of pneumonectomy? | {
"contexts": [
"Operative management of patients with persistent N2 disease after induction therapy is still debated.",
"One hundred fifty-three consecutive patients underwent pneumonectomy from January 1999 until July 2005; 28 patients (18.3%) had persistent N2 disease after induction therapy (group 1), 32 patients (20.9%) had pathologic stage N0 or N1 after induction therapy (group 2), and 93 patients (60.8%) with pathologic N2 disease underwent immediate surgery (group 3). Short-term end points were operative mortality at 30 and 90 days and major complications. Long-term end points were 5-year survival and disease-free survival rates.",
"Demographics of the three groups were similar (age, sex, side of operation, type of chemotherapy, smoking status, and comorbidity such as coronary artery disease, diabetes, and chronic obstructive pulmonary disease). Thirty-day postoperative mortality was 10.7% in group 1, 3.1% in group 2 (p = 0.257), and 4.3% in group 3 (p = 0.201); 90-day postoperative mortality was 10.7% in group 1, 12.5% in group 2 (p = 0.577), and 9.7% in group 3 (p = 0.558). Incidence of major postoperative complications was similar. Five-year survival rate was 32.2% (median, 28 months; 95% confidence interval, 7 to 43) in group 1, 34.8% (median, 27 months; 95% confidence interval, 7 to 47) in group 2 (p = 0.685), and 12.4% (median, 15 months; 95% confidence interval, 11 to 19) in group 3 (p = 0.127). No statistical difference was found in terms of 5-year event-free survival, or regarding the side of pneumonectomy."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Carcinoma, Non-Small-Cell Lung",
"Chemotherapy, Adjuvant",
"Cohort Studies",
"Female",
"Follow-Up Studies",
"Humans",
"Kaplan-Meier Estimate",
"Lung Neoplasms",
"Male",
"Middle Aged",
"Neoplasm Invasiveness",
"Neoplasm Recurrence, Local",
"Neoplasm Staging",
"Pneumonectomy",
"Probability",
"Radiotherapy, Adjuvant",
"Remission Induction",
"Retrospective Studies",
"Risk Assessment",
"Statistics, Nonparametric",
"Survival Analysis",
"Time Factors",
"Treatment Outcome"
]
} | Our results suggest that pneumonectomy is justified in patients with persistent N2 disease after induction chemotherapy. | no | [
{
"from": "human",
"value": "Question: Does persistent N2 disease after induction therapy jeopardize early and medium term outcomes of pneumonectomy?\nContext: {'contexts': ['Operative management of patients with persistent N2 disease after induction therapy is still debated.', 'One hundred fifty-three consecutive patients underwent pneumonectomy from January 1999 until July 2005; 28 patients (18.3%) had persistent N2 disease after induction therapy (group 1), 32 patients (20.9%) had pathologic stage N0 or N1 after induction therapy (group 2), and 93 patients (60.8%) with pathologic N2 disease underwent immediate surgery (group 3). Short-term end points were operative mortality at 30 and 90 days and major complications. Long-term end points were 5-year survival and disease-free survival rates.', 'Demographics of the three groups were similar (age, sex, side of operation, type of chemotherapy, smoking status, and comorbidity such as coronary artery disease, diabetes, and chronic obstructive pulmonary disease). Thirty-day postoperative mortality was 10.7% in group 1, 3.1% in group 2 (p = 0.257), and 4.3% in group 3 (p = 0.201); 90-day postoperative mortality was 10.7% in group 1, 12.5% in group 2 (p = 0.577), and 9.7% in group 3 (p = 0.558). Incidence of major postoperative complications was similar. Five-year survival rate was 32.2% (median, 28 months; 95% confidence interval, 7 to 43) in group 1, 34.8% (median, 27 months; 95% confidence interval, 7 to 47) in group 2 (p = 0.685), and 12.4% (median, 15 months; 95% confidence interval, 11 to 19) in group 3 (p = 0.127). No statistical difference was found in terms of 5-year event-free survival, or regarding the side of pneumonectomy.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Carcinoma, Non-Small-Cell Lung', 'Chemotherapy, Adjuvant', 'Cohort Studies', 'Female', 'Follow-Up Studies', 'Humans', 'Kaplan-Meier Estimate', 'Lung Neoplasms', 'Male', 'Middle Aged', 'Neoplasm Invasiveness', 'Neoplasm Recurrence, Local', 'Neoplasm Staging', 'Pneumonectomy', 'Probability', 'Radiotherapy, Adjuvant', 'Remission Induction', 'Retrospective Studies', 'Risk Assessment', 'Statistics, Nonparametric', 'Survival Analysis', 'Time Factors', 'Treatment Outcome']}"
},
{
"from": "gpt",
"value": "Answer: no"
}
]
|
18,562,950 | Are objective hot flashes negatively related to verbal memory performance in midlife women? | {
"contexts": [
"To test the hypothesis that hot flashes specifically relate to verbal memory performance by examining the relationship between objective hot flashes and cognitive test performance in women with moderate to severe vasomotor symptoms.",
"In an observational study, 29 midlife women (mean age, 53 y) with moderate to severe hot flashes provided measures of objective hot flashes with an ambulatory hot flash monitor, subjective hot flashes with a diary and questionnaire, and objective measures of verbal memory and other cognitive functions with standardized neuropsychological tests.",
"The mean number of objective hot flashes was 19.5 per day (range, 6 to 35), including 15.3 (range, 6 to 35) during waking hours and 4.2 (range, 0 to 9) during sleep. The mean sensitivity (ie, subjective detection of objectively measured hot flashes) was 60%. Regression analyses revealed that total number of objective hot flashes, sleep duration, and verbal knowledge were significant predictors of delayed verbal memory. Verbal fluency correlated positively with objective daytime hot flashes. Hot flashes did not predict performance on any of the other secondary cognitive measures (ie, attention, working memory, visual memory), although poor sleep predicted worse performance on several outcome measures."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Cognition",
"Female",
"Hot Flashes",
"Humans",
"Memory",
"Memory Disorders",
"Menopause",
"Middle Aged",
"Neuropsychological Tests",
"Regression Analysis",
"Severity of Illness Index",
"Surveys and Questionnaires",
"Verbal Learning",
"Women's Health"
]
} | Highly symptomatic women underreport the number of objective hot flashes that they experience by 43%. Verbal memory performance relates significantly to the objective number of hot flashes women experience but not to the number of hot flashes that they report. These findings suggest that physiological factors related to hot flashes, rather than psychological factors, predict poorer verbal memory function. | yes | [
{
"from": "human",
"value": "Question: Are objective hot flashes negatively related to verbal memory performance in midlife women?\nContext: {'contexts': ['To test the hypothesis that hot flashes specifically relate to verbal memory performance by examining the relationship between objective hot flashes and cognitive test performance in women with moderate to severe vasomotor symptoms.', 'In an observational study, 29 midlife women (mean age, 53 y) with moderate to severe hot flashes provided measures of objective hot flashes with an ambulatory hot flash monitor, subjective hot flashes with a diary and questionnaire, and objective measures of verbal memory and other cognitive functions with standardized neuropsychological tests.', 'The mean number of objective hot flashes was 19.5 per day (range, 6 to 35), including 15.3 (range, 6 to 35) during waking hours and 4.2 (range, 0 to 9) during sleep. The mean sensitivity (ie, subjective detection of objectively measured hot flashes) was 60%. Regression analyses revealed that total number of objective hot flashes, sleep duration, and verbal knowledge were significant predictors of delayed verbal memory. Verbal fluency correlated positively with objective daytime hot flashes. Hot flashes did not predict performance on any of the other secondary cognitive measures (ie, attention, working memory, visual memory), although poor sleep predicted worse performance on several outcome measures.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Cognition', 'Female', 'Hot Flashes', 'Humans', 'Memory', 'Memory Disorders', 'Menopause', 'Middle Aged', 'Neuropsychological Tests', 'Regression Analysis', 'Severity of Illness Index', 'Surveys and Questionnaires', 'Verbal Learning', \"Women's Health\"]}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,560,369 | Are serum phospholipid and cholesteryl ester fatty acids and estimated desaturase activities related to overweight and cardiovascular risk factors in adolescents? | {
"contexts": [
"The objective of this study was to describe the relation of serum fatty acids and desaturase activity (DA) to overweight, insulin sensitivity and cardiovascular disease (CVD) risk factors in adolescents.",
"The relations of % serum phospholipid (PL) and cholesteryl ester (CE) fatty acids and estimated DA with CVD risk factors were examined in 264 adolescents (average age 15 years). Fatty acids were determined by gas liquid chromotography. Surrogate measures of DA were expressed as ratios of serum fatty acids: Delta9 DA=16:0/16:1; Delta6 DA=20:3,n6/18:2,n6 (PL) or 18:3,n6/18:2,n6 (CE); and Delta5 DA=20:4,n6/20:3,n6. Spearman partial correlations of fatty acids (%) and DA ratios with CVD risk factors were reported, adjusting for age, sex, race, Tanner stage, energy intake and physical activity.",
"Overweight adolescents compared to normal weight had more adverse levels of CVD risk factors, composition of PL and CE fatty acids in serum, and Delta6 DA and Delta5 DA ratios. Linoleic acid was inversely related to body mass index (BMI), waist circumference and triglycerides (P<or=0.01). Dihomo-gamma-linolenic acid was positively related to BMI, waist, insulin, and triglycerides, and inversely related to high-density lipoprotein-cholesterol levels (P<or=0.01). Delta6 DA was adversely associated with most of the risk factors (P<or=0.01), whereas triglycerides and fasting insulin were beneficially related to Delta5 DA (P<or=0.01)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Body Mass Index",
"Cardiovascular Diseases",
"Cholesterol Esters",
"Fatty Acid Desaturases",
"Fatty Acids",
"Female",
"Humans",
"Insulin Resistance",
"Male",
"Overweight",
"Phospholipids",
"Risk Factors",
"Waist Circumference"
]
} | These findings support those observed in adults, that factors, such as type of dietary fat, physical activity, and obesity, may influence fatty acid metabolism and are important in the development of adverse CVD risk factors as early as adolescence. | yes | [
{
"from": "human",
"value": "Question: Are serum phospholipid and cholesteryl ester fatty acids and estimated desaturase activities related to overweight and cardiovascular risk factors in adolescents?\nContext: {'contexts': ['The objective of this study was to describe the relation of serum fatty acids and desaturase activity (DA) to overweight, insulin sensitivity and cardiovascular disease (CVD) risk factors in adolescents.', 'The relations of % serum phospholipid (PL) and cholesteryl ester (CE) fatty acids and estimated DA with CVD risk factors were examined in 264 adolescents (average age 15 years). Fatty acids were determined by gas liquid chromotography. Surrogate measures of DA were expressed as ratios of serum fatty acids: Delta9 DA=16:0/16:1; Delta6 DA=20:3,n6/18:2,n6 (PL) or 18:3,n6/18:2,n6 (CE); and Delta5 DA=20:4,n6/20:3,n6. Spearman partial correlations of fatty acids (%) and DA ratios with CVD risk factors were reported, adjusting for age, sex, race, Tanner stage, energy intake and physical activity.', 'Overweight adolescents compared to normal weight had more adverse levels of CVD risk factors, composition of PL and CE fatty acids in serum, and Delta6 DA and Delta5 DA ratios. Linoleic acid was inversely related to body mass index (BMI), waist circumference and triglycerides (P<or=0.01). Dihomo-gamma-linolenic acid was positively related to BMI, waist, insulin, and triglycerides, and inversely related to high-density lipoprotein-cholesterol levels (P<or=0.01). Delta6 DA was adversely associated with most of the risk factors (P<or=0.01), whereas triglycerides and fasting insulin were beneficially related to Delta5 DA (P<or=0.01).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Body Mass Index', 'Cardiovascular Diseases', 'Cholesterol Esters', 'Fatty Acid Desaturases', 'Fatty Acids', 'Female', 'Humans', 'Insulin Resistance', 'Male', 'Overweight', 'Phospholipids', 'Risk Factors', 'Waist Circumference']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,559,637 | Is baseline serum cholesterol selectively associated with motor speed and not rates of cognitive decline : the Women 's Health and Aging Study II? | {
"contexts": [
"Although several studies have investigated the association between cholesterol and dementia, few have examined cholesterol and decline across cognitive domains. We examined serum total and high-density lipoprotein (HDL) cholesterol, total-to-HDL ratio, and trajectories across cognitive domains.",
"Participants were 436 community-residing women (70-79 years old) in the Women's Health and Aging Study II; they were screened to be physically high-functioning and cognitively intact at baseline. Cognition and other health-related variables were assessed at five intervals spanning 9 years. Cognitive assessments included Trail Making Test Parts A (TMT-A) and B (TMT-B), Hopkins Verbal Learning Test-Revised, Purdue Pegboard, and Mini-Mental State Examination (MMSE). The association between baseline levels of serum lipids and cognitive trajectories were evaluated using Generalized Estimating Equations (GEE). Covariates included age, education, race, vascular disease, serum creatinine, depression, and lipid-lowering medications.",
"In multivariate analyses, baseline higher total (p =.02) and HDL (p =.03) cholesterol were associated with better performance on the Purdue Pegboard. Using clinical cholesterol cutoffs, baseline serum total cholesterol levels >240 mg/dL were associated with the best performance (p =.02). Baseline lipids were not associated with any other cognitive tests; there were no Lipid x Time interactions."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Cholesterol",
"Cholesterol, HDL",
"Cognition",
"Female",
"Humans",
"Lipoproteins, HDL",
"Motor Activity",
"Multivariate Analysis",
"Prospective Studies"
]
} | Higher baseline serum lipid levels predicted better performance over time on a measure of motor speed, but not memory or psychomotor or executive functioning in this population of elderly women. This association suggests that peripheral cholesterol levels, measured in late-life, may not be a good predictor of subsequent cognitive decline. Future research examining peripheral cholesterol over the life span and its relationship with cognition is needed. | yes | [
{
"from": "human",
"value": "Question: Is baseline serum cholesterol selectively associated with motor speed and not rates of cognitive decline : the Women 's Health and Aging Study II?\nContext: {'contexts': ['Although several studies have investigated the association between cholesterol and dementia, few have examined cholesterol and decline across cognitive domains. We examined serum total and high-density lipoprotein (HDL) cholesterol, total-to-HDL ratio, and trajectories across cognitive domains.', \"Participants were 436 community-residing women (70-79 years old) in the Women's Health and Aging Study II; they were screened to be physically high-functioning and cognitively intact at baseline. Cognition and other health-related variables were assessed at five intervals spanning 9 years. Cognitive assessments included Trail Making Test Parts A (TMT-A) and B (TMT-B), Hopkins Verbal Learning Test-Revised, Purdue Pegboard, and Mini-Mental State Examination (MMSE). The association between baseline levels of serum lipids and cognitive trajectories were evaluated using Generalized Estimating Equations (GEE). Covariates included age, education, race, vascular disease, serum creatinine, depression, and lipid-lowering medications.\", 'In multivariate analyses, baseline higher total (p =.02) and HDL (p =.03) cholesterol were associated with better performance on the Purdue Pegboard. Using clinical cholesterol cutoffs, baseline serum total cholesterol levels >240 mg/dL were associated with the best performance (p =.02). Baseline lipids were not associated with any other cognitive tests; there were no Lipid x Time interactions.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Cholesterol', 'Cholesterol, HDL', 'Cognition', 'Female', 'Humans', 'Lipoproteins, HDL', 'Motor Activity', 'Multivariate Analysis', 'Prospective Studies']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,558,091 | Does constitutive CXCL12 expression induce anoikis in colorectal carcinoma cells? | {
"contexts": [
"CXCL12 and CXCR4 signaling plays critical roles in development, homeostasis, and tumor metastasis. Previously, we have shown that epigenetic silencing of CXCL12 in colorectal and mammary carcinomas promotes metastasis. Anoikis is an essential process of colonic epithelial turnover and limits the metastatic progression of carcinoma. We sought to determine the role for anoikis in limiting tumor metastasis following reexpression of CXCL12 in human colorectal carcinoma cells.",
"Tumor formation and metastasis of colonic carcinoma cells was monitored using in vivo bioluminescence imaging. Anoikis was defined by using caspase-3/7, focal adhesion kinase (FAK) and p130Cas cleavage, DNA fragmentation, and cell survival assays. Phosphorylation of extracellular-regulated kinase-1/2 (ERK1/2) was monitored by immunoblot and immunohistochemistry, and activity was inhibited by using U0126.",
"Constitutive expression of CXCL12 in human colorectal carcinoma cells reduced orthotopic tumor formation and inhibited metastasis in severe combined immunodeficient mice. Further, CXCL12 expression induced apoptosis specifically in nonadherent colorectal carcinoma cells. Apoptotic cell death was preceded by hypophosphorylation and cleavage of FAK and p130Cas, leading to increased cellular detachment in culture, and depended on alterations in the extracellular matrix. Similar to in vivo colonic epithelium, CXCL12-induced anoikis of carcinoma cells depended on basal ERK1/2 activation."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Anoikis",
"Autocrine Communication",
"Butadienes",
"Caspase 3",
"Caspase 7",
"Cell Adhesion",
"Cell Survival",
"Chemokine CXCL12",
"Colorectal Neoplasms",
"Crk-Associated Substrate Protein",
"DNA Fragmentation",
"Focal Adhesion Protein-Tyrosine Kinases",
"Focal Adhesions",
"HCT116 Cells",
"HT29 Cells",
"Humans",
"Immunoblotting",
"Immunohistochemistry",
"Luminescent Measurements",
"Mice",
"Mice, SCID",
"Mitogen-Activated Protein Kinase 1",
"Mitogen-Activated Protein Kinase 3",
"Neoplasm Metastasis",
"Nitriles",
"Phosphorylation",
"Protein Kinase Inhibitors",
"Signal Transduction",
"Time Factors",
"Transfection"
]
} | These data significantly expand the current paradigm of chemokine signaling in carcinogenesis by showing that endogenous CXCL12, in marked contrast to exogenous ligand, inhibits tumor metastasis through increased anoikis. Altered ERK1/2 signaling provides a mechanism for the dichotomy between the physiologic and pathophysiologic roles of CXCL12-CXCR4 signaling in the intestinal epithelium. | yes | [
{
"from": "human",
"value": "Question: Does constitutive CXCL12 expression induce anoikis in colorectal carcinoma cells?\nContext: {'contexts': ['CXCL12 and CXCR4 signaling plays critical roles in development, homeostasis, and tumor metastasis. Previously, we have shown that epigenetic silencing of CXCL12 in colorectal and mammary carcinomas promotes metastasis. Anoikis is an essential process of colonic epithelial turnover and limits the metastatic progression of carcinoma. We sought to determine the role for anoikis in limiting tumor metastasis following reexpression of CXCL12 in human colorectal carcinoma cells.', 'Tumor formation and metastasis of colonic carcinoma cells was monitored using in vivo bioluminescence imaging. Anoikis was defined by using caspase-3/7, focal adhesion kinase (FAK) and p130Cas cleavage, DNA fragmentation, and cell survival assays. Phosphorylation of extracellular-regulated kinase-1/2 (ERK1/2) was monitored by immunoblot and immunohistochemistry, and activity was inhibited by using U0126.', 'Constitutive expression of CXCL12 in human colorectal carcinoma cells reduced orthotopic tumor formation and inhibited metastasis in severe combined immunodeficient mice. Further, CXCL12 expression induced apoptosis specifically in nonadherent colorectal carcinoma cells. Apoptotic cell death was preceded by hypophosphorylation and cleavage of FAK and p130Cas, leading to increased cellular detachment in culture, and depended on alterations in the extracellular matrix. Similar to in vivo colonic epithelium, CXCL12-induced anoikis of carcinoma cells depended on basal ERK1/2 activation.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Anoikis', 'Autocrine Communication', 'Butadienes', 'Caspase 3', 'Caspase 7', 'Cell Adhesion', 'Cell Survival', 'Chemokine CXCL12', 'Colorectal Neoplasms', 'Crk-Associated Substrate Protein', 'DNA Fragmentation', 'Focal Adhesion Protein-Tyrosine Kinases', 'Focal Adhesions', 'HCT116 Cells', 'HT29 Cells', 'Humans', 'Immunoblotting', 'Immunohistochemistry', 'Luminescent Measurements', 'Mice', 'Mice, SCID', 'Mitogen-Activated Protein Kinase 1', 'Mitogen-Activated Protein Kinase 3', 'Neoplasm Metastasis', 'Nitriles', 'Phosphorylation', 'Protein Kinase Inhibitors', 'Signal Transduction', 'Time Factors', 'Transfection']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,560,567 | Do formin 1-isoform IV deficient cells exhibit defects in cell spreading and focal adhesion formation? | {
"contexts": [
"Regulation of the cytoskeleton is a central feature of cell migration. The formin family of proteins controls the rate of actin nucleation at its barbed end. Thus, formins are predicted to contribute to several important cell processes such as locomotion, membrane ruffling, vesicle endocytosis, and stress fiber formation and disassociation.",
"In this study we investigated the functional role of Formin1-isoform4 (Fmn1-IV) by using genetically null primary cells that displayed augmented protrusive behaviour during wound healing and delayed cell spreading. Cells deficient of Fmn1-IV also showed reduced efficiency of focal adhesion formation. Additionally, we generated an enhanced green fluorescence protein (EGFP)-fused Fmn1-IV knock-in mouse to monitor the endogenous subcellular localization of Fmn1-IV. Its localization was found within the cytoplasm and along microtubules, yet it was largely excluded from adherens junctions."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Animals",
"Base Sequence",
"Cell Line",
"Cell Movement",
"DNA Primers",
"Fetal Proteins",
"Fluorescent Antibody Technique",
"Green Fluorescent Proteins",
"Mice",
"Mice, Transgenic",
"Microfilament Proteins",
"Microscopy, Electron",
"Nuclear Proteins",
"Protein Isoforms"
]
} | It was determined that Fmn1-IV, as an actin nucleator, contributes to protrusion of the cell's leading edge and focal adhesion formation, thus contributing to cell motility. | yes | [
{
"from": "human",
"value": "Question: Do formin 1-isoform IV deficient cells exhibit defects in cell spreading and focal adhesion formation?\nContext: {'contexts': ['Regulation of the cytoskeleton is a central feature of cell migration. The formin family of proteins controls the rate of actin nucleation at its barbed end. Thus, formins are predicted to contribute to several important cell processes such as locomotion, membrane ruffling, vesicle endocytosis, and stress fiber formation and disassociation.', 'In this study we investigated the functional role of Formin1-isoform4 (Fmn1-IV) by using genetically null primary cells that displayed augmented protrusive behaviour during wound healing and delayed cell spreading. Cells deficient of Fmn1-IV also showed reduced efficiency of focal adhesion formation. Additionally, we generated an enhanced green fluorescence protein (EGFP)-fused Fmn1-IV knock-in mouse to monitor the endogenous subcellular localization of Fmn1-IV. Its localization was found within the cytoplasm and along microtubules, yet it was largely excluded from adherens junctions.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Animals', 'Base Sequence', 'Cell Line', 'Cell Movement', 'DNA Primers', 'Fetal Proteins', 'Fluorescent Antibody Technique', 'Green Fluorescent Proteins', 'Mice', 'Mice, Transgenic', 'Microfilament Proteins', 'Microscopy, Electron', 'Nuclear Proteins', 'Protein Isoforms']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,573,676 | Does voxel-based morphometry reveal extra-nigral atrophy patterns associated with dopamine refractory cognitive and motor impairment in parkinsonism? | {
"contexts": [
"To determine overall patterns of brain atrophy associated with memory, executive function (EF) and dopamine non-responsive motor measures in older parkinsonian patients.",
"Forty-three older PD patients (>or=65 years) and matched controls underwent a neurological examination (Unified Parkinson's Disease Rating Scale, separated into dopamine responsive and dopamine non-responsive signs) and neuropsychological testing (memory: California Verbal Learning Test (CVLT)) and a composite of index of executive function (EF): Stroop Interference, Trail Making Test Part B, and digit ordering. All underwent volumetric MRI scans analyzed using voxel-based morphometry (VBM). Group comparisons, and the correlations between MRI gray and white matter volume and motor and cognitive measures were controlled for age, sex and intracranial volume. Cerebellar volume was independently measured using a validated extraction method.",
"Patients and controls were matched for demographics and global cognitive measures. VBM indicated significant gray matter (GM) atrophy in the cerebellum in PD and was confirmed independently. Poor memory was associated with GM atrophy in the left (uncus, middle temporal and fusiform gyri) and right temporal lobes and left putamen. Dopamine non-responsive motor signs and EF were associated with caudate atrophy. EF was also associated with GM atrophy in the middle temporal gyri, the left precuneus and cerebellum."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Analysis of Variance",
"Atrophy",
"Brain Mapping",
"Case-Control Studies",
"Cognition Disorders",
"Dopamine",
"Dopamine Agents",
"Female",
"Humans",
"Magnetic Resonance Imaging",
"Male",
"Movement Disorders",
"Neurologic Examination",
"Neuropsychological Tests",
"Parkinsonian Disorders",
"Statistics as Topic",
"Substantia Nigra"
]
} | Cortical and striatal atrophy were associated with dopamine non-responsive motor signs and cognitive impairment and provide a morphologic correlate for progression of PD. Cerebellar atrophy was found in older PD patients. | yes | [
{
"from": "human",
"value": "Question: Does voxel-based morphometry reveal extra-nigral atrophy patterns associated with dopamine refractory cognitive and motor impairment in parkinsonism?\nContext: {'contexts': ['To determine overall patterns of brain atrophy associated with memory, executive function (EF) and dopamine non-responsive motor measures in older parkinsonian patients.', \"Forty-three older PD patients (>or=65 years) and matched controls underwent a neurological examination (Unified Parkinson's Disease Rating Scale, separated into dopamine responsive and dopamine non-responsive signs) and neuropsychological testing (memory: California Verbal Learning Test (CVLT)) and a composite of index of executive function (EF): Stroop Interference, Trail Making Test Part B, and digit ordering. All underwent volumetric MRI scans analyzed using voxel-based morphometry (VBM). Group comparisons, and the correlations between MRI gray and white matter volume and motor and cognitive measures were controlled for age, sex and intracranial volume. Cerebellar volume was independently measured using a validated extraction method.\", 'Patients and controls were matched for demographics and global cognitive measures. VBM indicated significant gray matter (GM) atrophy in the cerebellum in PD and was confirmed independently. Poor memory was associated with GM atrophy in the left (uncus, middle temporal and fusiform gyri) and right temporal lobes and left putamen. Dopamine non-responsive motor signs and EF were associated with caudate atrophy. EF was also associated with GM atrophy in the middle temporal gyri, the left precuneus and cerebellum.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Analysis of Variance', 'Atrophy', 'Brain Mapping', 'Case-Control Studies', 'Cognition Disorders', 'Dopamine', 'Dopamine Agents', 'Female', 'Humans', 'Magnetic Resonance Imaging', 'Male', 'Movement Disorders', 'Neurologic Examination', 'Neuropsychological Tests', 'Parkinsonian Disorders', 'Statistics as Topic', 'Substantia Nigra']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,572,865 | Does [ Over-expression of hypoxia-inducible factor 1 alpha increase angiogenesis of LNCaP cells in vivo ]? | {
"contexts": [
"To observe the influence of hypoxia-inducible factor 1 alpha (HIF-1alpha) on angiogenesis in prostate carcinoma in vivo and to investigate its molecular mechanism.",
"LNCaP/HIF-1alpha and LNCaP cells were cultured, the level of PSA in the supernatant of the culture medium detected by ELISA assay before and after the transfection, and the cellular cycle measured by flow cytometry. Nude mouse models of subcutaneous tumor were established with LNCaP/HIF-1alpha and LNCaP cells, the tumor growth observed, and tumor specimens collected for immunohistochemical staining.",
"Compared with the LNCaP cells, LNCaP/HIF-1alpha cells showed an obviously decreased PSA level (t = 8.243, P < 0.05) and enhanced proliferous activity. The tumorigenesis rate increased and the tumorigenesis time advanced in the LNCaP/HIF-1alpha group of the nude mice. Immunohistochemistry displayed higher expressions of VEGF, iNOS and Ang-2 in the LNCaP/HIF-1alpha than in the LNCaP group."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Cell Cycle",
"Cell Line, Tumor",
"Cell Proliferation",
"Flow Cytometry",
"Gene Expression Regulation, Neoplastic",
"Humans",
"Hypoxia-Inducible Factor 1, alpha Subunit",
"Immunohistochemistry",
"Male",
"Mice",
"Mice, Nude",
"Neoplasms, Experimental",
"Neovascularization, Pathologic",
"Nitric Oxide Synthase Type II",
"Prostatic Neoplasms",
"Transfection",
"Transplantation, Heterologous",
"Tumor Burden",
"Vascular Endothelial Growth Factor A"
]
} | The over-expression of HIF-1alpha can up-regulate VEGF and iNOS involved in angiogenesis in vivo and contribute to the invasive potency of LNCaP cells. HIF-1alpha may have no influence on Ang-2 either in vitro or in vivo, while the expression of Ang-2 is regulated by other factors in vivo. | yes | [
{
"from": "human",
"value": "Question: Does [ Over-expression of hypoxia-inducible factor 1 alpha increase angiogenesis of LNCaP cells in vivo ]?\nContext: {'contexts': ['To observe the influence of hypoxia-inducible factor 1 alpha (HIF-1alpha) on angiogenesis in prostate carcinoma in vivo and to investigate its molecular mechanism.', 'LNCaP/HIF-1alpha and LNCaP cells were cultured, the level of PSA in the supernatant of the culture medium detected by ELISA assay before and after the transfection, and the cellular cycle measured by flow cytometry. Nude mouse models of subcutaneous tumor were established with LNCaP/HIF-1alpha and LNCaP cells, the tumor growth observed, and tumor specimens collected for immunohistochemical staining.', 'Compared with the LNCaP cells, LNCaP/HIF-1alpha cells showed an obviously decreased PSA level (t = 8.243, P < 0.05) and enhanced proliferous activity. The tumorigenesis rate increased and the tumorigenesis time advanced in the LNCaP/HIF-1alpha group of the nude mice. Immunohistochemistry displayed higher expressions of VEGF, iNOS and Ang-2 in the LNCaP/HIF-1alpha than in the LNCaP group.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Cell Cycle', 'Cell Line, Tumor', 'Cell Proliferation', 'Flow Cytometry', 'Gene Expression Regulation, Neoplastic', 'Humans', 'Hypoxia-Inducible Factor 1, alpha Subunit', 'Immunohistochemistry', 'Male', 'Mice', 'Mice, Nude', 'Neoplasms, Experimental', 'Neovascularization, Pathologic', 'Nitric Oxide Synthase Type II', 'Prostatic Neoplasms', 'Transfection', 'Transplantation, Heterologous', 'Tumor Burden', 'Vascular Endothelial Growth Factor A']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,544,621 | Does the T cell factor/beta-catenin antagonist PKF115-584 inhibit proliferation of adrenocortical carcinoma cells? | {
"contexts": [
"Mutations of the beta-catenin (CTNNB1) gene are frequently found in adrenocortical tumors. This has important consequences to deregulate the expression of transcriptional targets of the Wnt pathway, which may contribute to tumorigenesis.",
"The objective of the study was to investigate the effect of the small-molecule inhibitor of the T cell factor (Tcf)/beta-catenin complex PKF115-584 on beta-catenin-dependent transcription and proliferation of H295R adrenocortical tumor cells, which harbor mutations in CTNNB1 as well as the TP53 tumor suppressor gene.",
"Immunofluorescence, transient transfection, proliferation assays, and flow cytometric analyses were used.",
"Nuclear localization of beta-catenin and constitutive activation of beta-catenin-dependent transcription was observed in H295R cells. PKF115-584 dose-dependently inhibited beta-catenin-dependent transcription and H295R proliferation, even in the presence of increased steroidogenic factor-1 levels, which augment proliferation in this cell line. The drug had no effect on HeLa cells, a cell line in which the beta-catenin pathway is not activated. PKF115-584 decreased the percentage of H295R cells in S-phase and increased the percentage of apoptotic cells."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adrenal Cortex Neoplasms",
"Cell Proliferation",
"Genes, p53",
"Humans",
"Mutation",
"TCF Transcription Factors",
"Tumor Cells, Cultured",
"beta Catenin"
]
} | Inhibitors of the Tcf/beta-catenin complex may prove useful in the treatment of adrenocortical tumors in which multiple genetic alterations have accumulated. | yes | [
{
"from": "human",
"value": "Question: Does the T cell factor/beta-catenin antagonist PKF115-584 inhibit proliferation of adrenocortical carcinoma cells?\nContext: {'contexts': ['Mutations of the beta-catenin (CTNNB1) gene are frequently found in adrenocortical tumors. This has important consequences to deregulate the expression of transcriptional targets of the Wnt pathway, which may contribute to tumorigenesis.', 'The objective of the study was to investigate the effect of the small-molecule inhibitor of the T cell factor (Tcf)/beta-catenin complex PKF115-584 on beta-catenin-dependent transcription and proliferation of H295R adrenocortical tumor cells, which harbor mutations in CTNNB1 as well as the TP53 tumor suppressor gene.', 'Immunofluorescence, transient transfection, proliferation assays, and flow cytometric analyses were used.', 'Nuclear localization of beta-catenin and constitutive activation of beta-catenin-dependent transcription was observed in H295R cells. PKF115-584 dose-dependently inhibited beta-catenin-dependent transcription and H295R proliferation, even in the presence of increased steroidogenic factor-1 levels, which augment proliferation in this cell line. The drug had no effect on HeLa cells, a cell line in which the beta-catenin pathway is not activated. PKF115-584 decreased the percentage of H295R cells in S-phase and increased the percentage of apoptotic cells.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adrenal Cortex Neoplasms', 'Cell Proliferation', 'Genes, p53', 'Humans', 'Mutation', 'TCF Transcription Factors', 'Tumor Cells, Cultured', 'beta Catenin']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,568,197 | Does detection of hyaluronic acid receptor in human vocal fold by immunohistochemistry? | {
"contexts": [
"Hyaluronic acid receptor is a glycoprotein of the plasmatic membrane, and the CD44 is its representative, expressed in many cell types where it has the task of cell adhesion.",
"the goal of the present experimental study is to investigate the possibility of using immunohistochemistry to identify the distribution of hyaluronic acid along the vocal fold.",
"We resected the normal vocal folds from a normal 23 year-old male black individual. The slides were analyzed by means of a histomorphometric study, comparing the color intensity in the superficial, middle and deep layers of the lamina propria. In the silanized slides we used immunohistochemistry, and evaluated the slides under light microscopy with 40x magnification, and the color changed to brown when there was a reaction with the receptor for hyaluronic acid.",
"Immunohistochemical findings showed the presence of hyaluronic acid receptors in the epithelium covering the vocal fold, being more concentrated in the central region of the vocal fold."
],
"labels": [
"UNLABELLED",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"African Continental Ancestry Group",
"Alcian Blue",
"Cadaver",
"Coloring Agents",
"European Continental Ancestry Group",
"Humans",
"Hyaluronan Receptors",
"Hyaluronic Acid",
"Immunohistochemistry",
"Male",
"Vocal Cords"
]
} | immunohistochemistry, used to assess the distribution of hyaluronic acid receptors in the central portion of the vocal fold, proved it to be present in the vocal fold epithelium and it prevailed in its middle third. | yes | [
{
"from": "human",
"value": "Question: Does detection of hyaluronic acid receptor in human vocal fold by immunohistochemistry?\nContext: {'contexts': ['Hyaluronic acid receptor is a glycoprotein of the plasmatic membrane, and the CD44 is its representative, expressed in many cell types where it has the task of cell adhesion.', 'the goal of the present experimental study is to investigate the possibility of using immunohistochemistry to identify the distribution of hyaluronic acid along the vocal fold.', 'We resected the normal vocal folds from a normal 23 year-old male black individual. The slides were analyzed by means of a histomorphometric study, comparing the color intensity in the superficial, middle and deep layers of the lamina propria. In the silanized slides we used immunohistochemistry, and evaluated the slides under light microscopy with 40x magnification, and the color changed to brown when there was a reaction with the receptor for hyaluronic acid.', 'Immunohistochemical findings showed the presence of hyaluronic acid receptors in the epithelium covering the vocal fold, being more concentrated in the central region of the vocal fold.'], 'labels': ['UNLABELLED', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'African Continental Ancestry Group', 'Alcian Blue', 'Cadaver', 'Coloring Agents', 'European Continental Ancestry Group', 'Humans', 'Hyaluronan Receptors', 'Hyaluronic Acid', 'Immunohistochemistry', 'Male', 'Vocal Cords']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,570,934 | Are sophorolipids and their derivatives lethal against human pancreatic cancer cells? | {
"contexts": [
"We have previously demonstrated that sophorolipids, a class of easily chemoenzymatically modifiable glycolipids, possess anti-inflammatory effects in vitro and in vivo. Since glycolipids have been shown to have anticancer activity, we investigated the effects of sophorolipids and their derivatives against pancreatic cancer.",
"Human pancreatic carcinoma cells were treated with increasing concentrations of sophorolipid natural mixture or select derivatives (ethyl ester, methyl ester, ethyl ester monoacetate, ethyl ester diacetate, acidic sophorolipid [AS], lactonic sophorolipid diacetate [LSD]) for 24 h and assessed for cell necrosis (cytotoxicity-lactate dehydrogenase release). Controls consisted of cells treated with media or vehicle alone and sophorolipid treatment of peripheral blood mononuclear cells.",
"Sophorolipids demonstrated anticancer activity against human pancreatic carcinoma cells. Natural mixture mediated consistent cytotoxicity at all doses tested (20 +/- 4%). However, methyl ester derivative mediated much greater levels of cytotoxicity (63 +/- 5%) compared with other derivatives (ethyl ester diacetate, 36 +/- 6%, ethyl ester monoacetate, 18 +/- 7%; P < 0.05). In contrast, LSD- and AS-mediated toxicity was inversely proportional with dose (LSD, 40.3% at 0.5 mg/mL, 3.4% at 2.0 mg/mL; AS, 49% at 0.5 mg/mL, 0% at 2.0 mg/mL). Sophorolipid treatment did not affect peripheral blood mononuclear cells at all doses tested."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adenocarcinoma",
"Antineoplastic Agents",
"Cell Line, Tumor",
"Dose-Response Relationship, Drug",
"Glycolipids",
"Humans",
"Pancreatic Neoplasms"
]
} | These results suggest that sophorolipids and select derivatives may be effective in treating human pancreatic cancer. Furthermore select derivatives may use different mechanisms toward this end. The ability to chemoenzymatically modify sophorolipids can provide effective lead compounds toward the treatment of pancreatic cancer. | yes | [
{
"from": "human",
"value": "Question: Are sophorolipids and their derivatives lethal against human pancreatic cancer cells?\nContext: {'contexts': ['We have previously demonstrated that sophorolipids, a class of easily chemoenzymatically modifiable glycolipids, possess anti-inflammatory effects in vitro and in vivo. Since glycolipids have been shown to have anticancer activity, we investigated the effects of sophorolipids and their derivatives against pancreatic cancer.', 'Human pancreatic carcinoma cells were treated with increasing concentrations of sophorolipid natural mixture or select derivatives (ethyl ester, methyl ester, ethyl ester monoacetate, ethyl ester diacetate, acidic sophorolipid [AS], lactonic sophorolipid diacetate [LSD]) for 24 h and assessed for cell necrosis (cytotoxicity-lactate dehydrogenase release). Controls consisted of cells treated with media or vehicle alone and sophorolipid treatment of peripheral blood mononuclear cells.', 'Sophorolipids demonstrated anticancer activity against human pancreatic carcinoma cells. Natural mixture mediated consistent cytotoxicity at all doses tested (20 +/- 4%). However, methyl ester derivative mediated much greater levels of cytotoxicity (63 +/- 5%) compared with other derivatives (ethyl ester diacetate, 36 +/- 6%, ethyl ester monoacetate, 18 +/- 7%; P < 0.05). In contrast, LSD- and AS-mediated toxicity was inversely proportional with dose (LSD, 40.3% at 0.5 mg/mL, 3.4% at 2.0 mg/mL; AS, 49% at 0.5 mg/mL, 0% at 2.0 mg/mL). Sophorolipid treatment did not affect peripheral blood mononuclear cells at all doses tested.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adenocarcinoma', 'Antineoplastic Agents', 'Cell Line, Tumor', 'Dose-Response Relationship, Drug', 'Glycolipids', 'Humans', 'Pancreatic Neoplasms']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,570,930 | Are homeobox genes Hoxd3 and Hoxd8 differentially expressed in fetal mouse excisional wounds? | {
"contexts": [
"Cell signaling pathways underlying wound repair are under extensive investigation; however, there is still a poor understanding of the mechanisms orchestrating these processes. Hox genes, which are a subgroup of homeobox genes, encode for a family of transcription factors that play a critical role in tissue migration and cell differentiation during embryogenesis and may also serve as master regulatory genes of postnatal wound repair. We have developed a fetal excisional wound healing model whereby mid-gestational wounds heal in a regenerative manner while late-gestational wounds display scar formation. We theorize that Hoxd3 and Hoxd8 will be differentially expressed in mid- and late-gestational wounds compared with normal skin.",
"Pregnant FVB mice underwent hysterotomy at mid (E15)- or late (E18)-gestational time points, and 3-mm excisional wounds were made on the dorsum of each fetus. Wound samples (w) were collected at the site of injury as well as near wound normal skin (nwc) on the same fetus. Control (c) skin samples were also obtained from unwounded adjacent fetuses. Samples were harvested at 3 and 6 h and real-time polymerase chain reaction was performed for Hoxd3 and Hoxd8 and normalized to glyceraldehyde-3-phosphate dehydrogenase. Data were analyzed by analysis of variance with statistical significance of P < 0.05.",
"Hoxd3 levels were increased in all of the mid-gestational groups, with a significant increase at 3 h compared with late-gestational control groups. In the 3-h time group, Hoxd8 is increased in mid-gestational wounds compared with late-gestational control skin. This is repeated in the 6-h time group, where Hoxd8 is increased in mid-gestational wounds compared with all groups. Also, Hoxd8 in the mid-gestational near wound controls is significantly greater than that in the late-gestational near wound control and control groups."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Cicatrix",
"Female",
"Fetus",
"Gene Expression Regulation, Developmental",
"Gestational Age",
"Homeodomain Proteins",
"Mice",
"Pregnancy",
"Signal Transduction",
"Skin",
"Transcription Factors",
"Up-Regulation",
"Wound Healing",
"Wounds and Injuries"
]
} | These data suggest that Hoxd3 is constitutively expressed in the skin of mid-gestational mice. However, Hoxd8 expression is increased in the mid-gestational wounds compared with normal control groups and late gestational wounds, suggesting that it may play a role in scarless wound repair. | yes | [
{
"from": "human",
"value": "Question: Are homeobox genes Hoxd3 and Hoxd8 differentially expressed in fetal mouse excisional wounds?\nContext: {'contexts': ['Cell signaling pathways underlying wound repair are under extensive investigation; however, there is still a poor understanding of the mechanisms orchestrating these processes. Hox genes, which are a subgroup of homeobox genes, encode for a family of transcription factors that play a critical role in tissue migration and cell differentiation during embryogenesis and may also serve as master regulatory genes of postnatal wound repair. We have developed a fetal excisional wound healing model whereby mid-gestational wounds heal in a regenerative manner while late-gestational wounds display scar formation. We theorize that Hoxd3 and Hoxd8 will be differentially expressed in mid- and late-gestational wounds compared with normal skin.', 'Pregnant FVB mice underwent hysterotomy at mid (E15)- or late (E18)-gestational time points, and 3-mm excisional wounds were made on the dorsum of each fetus. Wound samples (w) were collected at the site of injury as well as near wound normal skin (nwc) on the same fetus. Control (c) skin samples were also obtained from unwounded adjacent fetuses. Samples were harvested at 3 and 6 h and real-time polymerase chain reaction was performed for Hoxd3 and Hoxd8 and normalized to glyceraldehyde-3-phosphate dehydrogenase. Data were analyzed by analysis of variance with statistical significance of P < 0.05.', 'Hoxd3 levels were increased in all of the mid-gestational groups, with a significant increase at 3 h compared with late-gestational control groups. In the 3-h time group, Hoxd8 is increased in mid-gestational wounds compared with late-gestational control skin. This is repeated in the 6-h time group, where Hoxd8 is increased in mid-gestational wounds compared with all groups. Also, Hoxd8 in the mid-gestational near wound controls is significantly greater than that in the late-gestational near wound control and control groups.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Cicatrix', 'Female', 'Fetus', 'Gene Expression Regulation, Developmental', 'Gestational Age', 'Homeodomain Proteins', 'Mice', 'Pregnancy', 'Signal Transduction', 'Skin', 'Transcription Factors', 'Up-Regulation', 'Wound Healing', 'Wounds and Injuries']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,548,919 | Does type 2 diabetes impair implant osseointegration capacity in rats? | {
"contexts": [
"The effect of type 2 diabetes mellitus (adult-onset non-insulin-dependent), which is the most common form of diabetes in humans, on osseointegration capacity has not been addressed in an appropriate animal model. This study histologically and histomorphometrically examines bone healing around titanium implants in the type 2 diabetes rat model.",
"Titanium implants with a chamber were placed into the femurs of normal male rats and genetically modified male rats with a close symptomatic resemblance to human type 2 diabetes, as characterized by late-onset hyperglycemia and obesity. Cross-sectional histology for the tissue grown into the implant chamber was examined.",
"Bone volume around implants was consistently (from weeks 4 to 8 postimplantation) smaller for the diabetes group than for the control group in the cortical area, while the bone volume in the marrow area was not affected by the diabetes. Bone-implant contact percentage was considerably lower for the diabetes group in both the cortical and marrow areas, with the week 4 bone-implant contact in the cortical area being 12% for the diabetes group and 61% for the control group. A 2-fold difference remained at week 8. Bone morphogenesis in the diabetic rats was characterized by fragmented bone tissues and extensive soft tissue intervention."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Analysis of Variance",
"Animals",
"Dental Implantation, Endosseous",
"Dental Implants",
"Diabetes Mellitus, Type 2",
"Femur",
"Implants, Experimental",
"Male",
"Models, Animal",
"Osseointegration",
"Rats",
"Rats, Long-Evans",
"Rats, Mutant Strains",
"Titanium"
]
} | Type 2 diabetes mellitus impaired osseointegration capacity disproportionally between the cortical bone and bone marrow areas. The reduction of the bone quantity in the cortical area and the bone-implant contact in both the cortical and marrow areas was remarkable. | yes | [
{
"from": "human",
"value": "Question: Does type 2 diabetes impair implant osseointegration capacity in rats?\nContext: {'contexts': ['The effect of type 2 diabetes mellitus (adult-onset non-insulin-dependent), which is the most common form of diabetes in humans, on osseointegration capacity has not been addressed in an appropriate animal model. This study histologically and histomorphometrically examines bone healing around titanium implants in the type 2 diabetes rat model.', 'Titanium implants with a chamber were placed into the femurs of normal male rats and genetically modified male rats with a close symptomatic resemblance to human type 2 diabetes, as characterized by late-onset hyperglycemia and obesity. Cross-sectional histology for the tissue grown into the implant chamber was examined.', 'Bone volume around implants was consistently (from weeks 4 to 8 postimplantation) smaller for the diabetes group than for the control group in the cortical area, while the bone volume in the marrow area was not affected by the diabetes. Bone-implant contact percentage was considerably lower for the diabetes group in both the cortical and marrow areas, with the week 4 bone-implant contact in the cortical area being 12% for the diabetes group and 61% for the control group. A 2-fold difference remained at week 8. Bone morphogenesis in the diabetic rats was characterized by fragmented bone tissues and extensive soft tissue intervention.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Analysis of Variance', 'Animals', 'Dental Implantation, Endosseous', 'Dental Implants', 'Diabetes Mellitus, Type 2', 'Femur', 'Implants, Experimental', 'Male', 'Models, Animal', 'Osseointegration', 'Rats', 'Rats, Long-Evans', 'Rats, Mutant Strains', 'Titanium']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,552,872 | Is emodin a novel alkaline nuclease inhibitor that suppresses herpes simplex virus type 1 yields in cell cultures? | {
"contexts": [
"Most antiviral therapies directed against herpes simplex virus (HSV) infections are limited to a small group of nucleoside analogues that target the viral polymerase. Extensive clinical use of these drugs has led to the emergence of resistant viral strains, mainly in immunocompromised patients. This highlights the need for the development of new anti-herpesviral drugs with novel targets. Herein the effects of a plant anthraquinone, emodin, on the HSV-1 alkaline nuclease activity and virus yields were investigated.",
"HSV-1 alkaline nuclease activity was examined by nuclease activity assay. Inhibition of virus yields was measured by plaque reduction assay and immunohistochemical staining. Interaction between emodin and alkaline nuclease was analysed by docking technology.",
"Emodin specifically inhibited the nuclease activity of HSV-1 UL12 alkaline nuclease in a biochemical assay. Plaque reduction assay revealed that emodin reduced the plaque formation with an EC(50) of 21.5+/-4.4 muM. Immunohistochemical staining using the anti-nucleocapsid protein antibody demonstrated that emodin induced the accumulation of viral nucleocapsids in the nucleus in a dose-dependent manner. Docking analysis further suggested that the inhibitory effect of emodin on the UL12 activity may result from the interaction between emodin and critical catalytic amino acid residues of UL12."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Capsid",
"Cell Culture Techniques",
"Cells, Cultured",
"Cercopithecus aethiops",
"Emodin",
"Herpesvirus 1, Human",
"Recombinant Proteins",
"Ribonucleases",
"Vero Cells",
"Virus Replication"
]
} | Our findings suggest that emodin is a potent anti-HSV agent that inhibits the yields of HSV-1 via the suppression of a novel target, UL12. | yes | [
{
"from": "human",
"value": "Question: Is emodin a novel alkaline nuclease inhibitor that suppresses herpes simplex virus type 1 yields in cell cultures?\nContext: {'contexts': ['Most antiviral therapies directed against herpes simplex virus (HSV) infections are limited to a small group of nucleoside analogues that target the viral polymerase. Extensive clinical use of these drugs has led to the emergence of resistant viral strains, mainly in immunocompromised patients. This highlights the need for the development of new anti-herpesviral drugs with novel targets. Herein the effects of a plant anthraquinone, emodin, on the HSV-1 alkaline nuclease activity and virus yields were investigated.', 'HSV-1 alkaline nuclease activity was examined by nuclease activity assay. Inhibition of virus yields was measured by plaque reduction assay and immunohistochemical staining. Interaction between emodin and alkaline nuclease was analysed by docking technology.', 'Emodin specifically inhibited the nuclease activity of HSV-1 UL12 alkaline nuclease in a biochemical assay. Plaque reduction assay revealed that emodin reduced the plaque formation with an EC(50) of 21.5+/-4.4 muM. Immunohistochemical staining using the anti-nucleocapsid protein antibody demonstrated that emodin induced the accumulation of viral nucleocapsids in the nucleus in a dose-dependent manner. Docking analysis further suggested that the inhibitory effect of emodin on the UL12 activity may result from the interaction between emodin and critical catalytic amino acid residues of UL12.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Capsid', 'Cell Culture Techniques', 'Cells, Cultured', 'Cercopithecus aethiops', 'Emodin', 'Herpesvirus 1, Human', 'Recombinant Proteins', 'Ribonucleases', 'Vero Cells', 'Virus Replication']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,552,876 | Do low concentrations of tetrodotoxin interact with tetrodotoxin-resistant voltage-gated sodium channels? | {
"contexts": [
"Tetrodotoxin (TTX) is used to distinguish between two classes of voltage-gated sodium channel (VGSC)--TTX sensitive (TTXS) and TTX resistant (TTXR). The resistance of TTXR VGSCs is thought to result from a low binding affinity of TTX, although at high TTX concentrations channel block does occur. Here, we show that, at concentrations below those which produce block, TTX can bind to TTXR VGSCs.",
"Whole-cell voltage clamp recordings were made from dissociated rat dorsal root ganglion neurones that expressed both TTXS and TTXR sodium currents. Voltage-gated calcium currents were blocked by 10 microM extracellular lanthanum chloride. TTXS, but not TTXR, current was suppressed by using a holding potential of -50 mV, and the effect of TTX on the isolated TTXR current was explored.",
"Extracellular application of 0.5 microM TTX produced a 40% increase in TTXR current amplitude, a negative shift in the voltage-dependence of current activation (approximately -8 mV) and inactivation (approximately -10 mV) and increased rates of current activation and inactivation. The effect of TTX on current amplitude was dose-dependent (EC50 = 364 nM). Removal of lanthanum prevented the effect of TTX on TTXR current amplitude, whereas reducing extracellular calcium did not."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Calcium",
"Cells, Cultured",
"Dose-Response Relationship, Drug",
"Ganglia, Spinal",
"Lanthanum",
"Membrane Potentials",
"NAV1.8 Voltage-Gated Sodium Channel",
"NAV1.9 Voltage-Gated Sodium Channel",
"Nerve Tissue Proteins",
"Neurons",
"Neuropeptides",
"Rats",
"Rats, Inbred Lew",
"Rats, Sprague-Dawley",
"Sodium Channel Blockers",
"Sodium Channels",
"Tetrodotoxin",
"Time Factors"
]
} | The findings are consistent with an interpretation that TTX relieves a tonic block of the TTXR VGSC by lanthanum. We conclude that TTX binds to the TTXR VGSC at low concentrations, without blocking it. This appears to be the first demonstration of a clear distinction between binding affinity and blocking potency of a channel-blocking agent. | yes | [
{
"from": "human",
"value": "Question: Do low concentrations of tetrodotoxin interact with tetrodotoxin-resistant voltage-gated sodium channels?\nContext: {'contexts': ['Tetrodotoxin (TTX) is used to distinguish between two classes of voltage-gated sodium channel (VGSC)--TTX sensitive (TTXS) and TTX resistant (TTXR). The resistance of TTXR VGSCs is thought to result from a low binding affinity of TTX, although at high TTX concentrations channel block does occur. Here, we show that, at concentrations below those which produce block, TTX can bind to TTXR VGSCs.', 'Whole-cell voltage clamp recordings were made from dissociated rat dorsal root ganglion neurones that expressed both TTXS and TTXR sodium currents. Voltage-gated calcium currents were blocked by 10 microM extracellular lanthanum chloride. TTXS, but not TTXR, current was suppressed by using a holding potential of -50 mV, and the effect of TTX on the isolated TTXR current was explored.', 'Extracellular application of 0.5 microM TTX produced a 40% increase in TTXR current amplitude, a negative shift in the voltage-dependence of current activation (approximately -8 mV) and inactivation (approximately -10 mV) and increased rates of current activation and inactivation. The effect of TTX on current amplitude was dose-dependent (EC50 = 364 nM). Removal of lanthanum prevented the effect of TTX on TTXR current amplitude, whereas reducing extracellular calcium did not.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Calcium', 'Cells, Cultured', 'Dose-Response Relationship, Drug', 'Ganglia, Spinal', 'Lanthanum', 'Membrane Potentials', 'NAV1.8 Voltage-Gated Sodium Channel', 'NAV1.9 Voltage-Gated Sodium Channel', 'Nerve Tissue Proteins', 'Neurons', 'Neuropeptides', 'Rats', 'Rats, Inbred Lew', 'Rats, Sprague-Dawley', 'Sodium Channel Blockers', 'Sodium Channels', 'Tetrodotoxin', 'Time Factors']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,552,877 | Do vitamin D and glucocorticoids differentially modulate chemokine expression in human airway smooth muscle cells? | {
"contexts": [
"Chemokines play a critical role in the pathogenesis of asthma and facilitate the recruitment of inflammatory cells in the airways. Evidence now suggests that airway smooth muscle (ASM) may serve as a source of chemokines in inflamed airways. Although vitamin D has potent anti-inflammatory properties in vitro in some cell types, its effects on ASM cells remain unclear. Here, we investigated whether 1alpha, 25-dihydroxy vitamin D3 (calcitriol) modulated chemokine production in ASM.",
"Human ASM cell cultures were derived from tracheal samples taken during surgery. ASM cells were treated with tumour necrosis factor alpha (TNFalpha) and/or interferon gamma (IFNgamma) for 24 h in the presence of calcitriol and/or the glucocorticoid fluticasone added 2 h before. RANTES (regulated upon activation, normal T-cell expressed and secreted), interferon-inducible protein 10 (IP-10) and fractalkine (FKN) levels in cell supernatants were measured by ELISA.",
"In TNFalpha-treated cells, calcitriol inhibited RANTES and IP-10 secretion in a concentration-dependent manner. FKN levels were negligible. In TNFalpha/IFNgamma-treated cells, whereas fluticasone or calcitriol alone partially inhibited RANTES secretion (by 38 and 20%, respectively), the combination of both drugs additively inhibited RANTES secretion (by 60%). No effect was observed on IP-10 secretion. Whereas fluticasone enhanced FKN secretion (by 50%), calcitriol significantly decreased FKN levels (by 50%). Interestingly, calcitriol blocked the stimulatory effect of fluticasone on FKN secretion, which was inhibited by 60% with the combination of calcitriol and fluticasone."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Androstadienes",
"Anti-Asthmatic Agents",
"Anti-Inflammatory Agents",
"Calcitriol",
"Cells, Cultured",
"Chemokine CCL5",
"Chemokine CX3CL1",
"Chemokine CXCL10",
"Chemokines",
"Dose-Response Relationship, Drug",
"Drug Resistance",
"Fluticasone",
"Glucocorticoids",
"Humans",
"Interferon-gamma",
"Muscle, Smooth",
"Myocytes, Smooth Muscle",
"Receptors, Calcitriol",
"Time Factors",
"Trachea",
"Tumor Necrosis Factor-alpha"
]
} | These findings suggest that vitamin D uniquely modulates human ASM expression of chemokines and may exert some beneficial effects in the treatment of steroid-resistant patients with asthma. | yes | [
{
"from": "human",
"value": "Question: Do vitamin D and glucocorticoids differentially modulate chemokine expression in human airway smooth muscle cells?\nContext: {'contexts': ['Chemokines play a critical role in the pathogenesis of asthma and facilitate the recruitment of inflammatory cells in the airways. Evidence now suggests that airway smooth muscle (ASM) may serve as a source of chemokines in inflamed airways. Although vitamin D has potent anti-inflammatory properties in vitro in some cell types, its effects on ASM cells remain unclear. Here, we investigated whether 1alpha, 25-dihydroxy vitamin D3 (calcitriol) modulated chemokine production in ASM.', 'Human ASM cell cultures were derived from tracheal samples taken during surgery. ASM cells were treated with tumour necrosis factor alpha (TNFalpha) and/or interferon gamma (IFNgamma) for 24 h in the presence of calcitriol and/or the glucocorticoid fluticasone added 2 h before. RANTES (regulated upon activation, normal T-cell expressed and secreted), interferon-inducible protein 10 (IP-10) and fractalkine (FKN) levels in cell supernatants were measured by ELISA.', 'In TNFalpha-treated cells, calcitriol inhibited RANTES and IP-10 secretion in a concentration-dependent manner. FKN levels were negligible. In TNFalpha/IFNgamma-treated cells, whereas fluticasone or calcitriol alone partially inhibited RANTES secretion (by 38 and 20%, respectively), the combination of both drugs additively inhibited RANTES secretion (by 60%). No effect was observed on IP-10 secretion. Whereas fluticasone enhanced FKN secretion (by 50%), calcitriol significantly decreased FKN levels (by 50%). Interestingly, calcitriol blocked the stimulatory effect of fluticasone on FKN secretion, which was inhibited by 60% with the combination of calcitriol and fluticasone.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Androstadienes', 'Anti-Asthmatic Agents', 'Anti-Inflammatory Agents', 'Calcitriol', 'Cells, Cultured', 'Chemokine CCL5', 'Chemokine CX3CL1', 'Chemokine CXCL10', 'Chemokines', 'Dose-Response Relationship, Drug', 'Drug Resistance', 'Fluticasone', 'Glucocorticoids', 'Humans', 'Interferon-gamma', 'Muscle, Smooth', 'Myocytes, Smooth Muscle', 'Receptors, Calcitriol', 'Time Factors', 'Trachea', 'Tumor Necrosis Factor-alpha']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,567,558 | Is survival status of veterans with lung cancer poorer than that among civilians due to age and sex differences : a study of Chinese veterans in Taiwan? | {
"contexts": [
"This study was undertaken to analyze and compare the clinical characteristics and survival difference among veterans and civilians in Taiwan with lung cancer, especially non-small-cell lung cancer, and to determine whether or not veterans have a poorer prognosis than civilians.",
"We retrospectively reviewed the medical records and computer files of lung cancer patients diagnosed between 1996 and 2000 at our hospital. Patients' clinical characteristics, marital status, staging, treatment modality, and overall survival were analyzed and compared, based on the patients' standing as veterans or civilians.",
"During this period, 3,727 lung cancer patients (2,386 veterans, 1,341 civilians) were diagnosed. The overall survival of all lung cancer patients showed that civilians had better survival than veterans (median, 12 months vs. 8 months, p < 0.001). Survival of non-small-cell lung cancer patients was also better for civilians than veterans (median, 13 months vs. 9 months, p < 0.001). Surgery was the main treatment modality in both stage I and II civilians and veterans. A greater proportion of veterans in stage II and III received radiotherapy than civilians in the same stage, with a statistically significant difference in stage III patients (p < 0.001). Multivariate survival analysis showed that age and sex were independent risk factors for mortality, while standing (veteran or civilian) was not, in both all lung cancers and non-small-cell lung cancer alone."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Age Factors",
"Aged",
"Carcinoma, Non-Small-Cell Lung",
"Female",
"Humans",
"Lung Neoplasms",
"Male",
"Marriage",
"Middle Aged",
"Multivariate Analysis",
"Neoplasm Staging",
"Retrospective Studies",
"Sex Characteristics",
"Survival Rate",
"Taiwan",
"Veterans"
]
} | Veterans, who mainly came from China, had a poorer prognosis than civilians when suffering from lung cancer in Taiwan, due to age and gender, rather than standing. | yes | [
{
"from": "human",
"value": "Question: Is survival status of veterans with lung cancer poorer than that among civilians due to age and sex differences : a study of Chinese veterans in Taiwan?\nContext: {'contexts': ['This study was undertaken to analyze and compare the clinical characteristics and survival difference among veterans and civilians in Taiwan with lung cancer, especially non-small-cell lung cancer, and to determine whether or not veterans have a poorer prognosis than civilians.', \"We retrospectively reviewed the medical records and computer files of lung cancer patients diagnosed between 1996 and 2000 at our hospital. Patients' clinical characteristics, marital status, staging, treatment modality, and overall survival were analyzed and compared, based on the patients' standing as veterans or civilians.\", 'During this period, 3,727 lung cancer patients (2,386 veterans, 1,341 civilians) were diagnosed. The overall survival of all lung cancer patients showed that civilians had better survival than veterans (median, 12 months vs. 8 months, p < 0.001). Survival of non-small-cell lung cancer patients was also better for civilians than veterans (median, 13 months vs. 9 months, p < 0.001). Surgery was the main treatment modality in both stage I and II civilians and veterans. A greater proportion of veterans in stage II and III received radiotherapy than civilians in the same stage, with a statistically significant difference in stage III patients (p < 0.001). Multivariate survival analysis showed that age and sex were independent risk factors for mortality, while standing (veteran or civilian) was not, in both all lung cancers and non-small-cell lung cancer alone.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Age Factors', 'Aged', 'Carcinoma, Non-Small-Cell Lung', 'Female', 'Humans', 'Lung Neoplasms', 'Male', 'Marriage', 'Middle Aged', 'Multivariate Analysis', 'Neoplasm Staging', 'Retrospective Studies', 'Sex Characteristics', 'Survival Rate', 'Taiwan', 'Veterans']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,572,757 | Do antiviral resistance mutations potentiate hepatitis B virus immune evasion through disruption of its surface antigen a determinant? | {
"contexts": [
"The hepatitis B virus (HBV) pol gene overlaps the S gene encoding surface antigen (HBsAg). It has been reported previously that drug-induced changes in HBsAg alter its binding to sera from humans immunized against HBV. We investigate here the changes to specific epitopes in the a determinant (the major target of neutralizing antibody) caused by a number of drug-resistant mutations.",
"Recombinant HBsAgs, produced by transfection of Chinese hamster ovary cells with S gene plasmids into which lamivudine, adefovir and entecavir resistance and common antibody-escape mutations had been introduced, were probed with monoclonal antibodies to epitopes in the first and second loops of the a determinant.",
"The mutations rtF166L/sF158Y (lamivudine-associated, compensatory) and rtl169T/sF161L (entecavir-associated, primary) acting alone, and the mutations rtV173L/sE164D (lamivudine-associated, compensatory) and rtSilent/sD144E (antibody escape-associated) each when combined with rtM204V/sl195M (lamivudine-associated, primary) led to decreases in antibody reactivity to epitopes in the first or second loop, or in both loops. The rtM204V/sl195M + rtV173L/sE164D mutations yielded an epitope-antibody profile similar to the rtR153Q/sG145R vaccine escape mutant. The rtM204V/sl195M mutation combined with the rtF166L/sF158Y or rtR153Q/sG145R mutation restored reactivity to second-loop epitopes previously abrogated by single mutations."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adenine",
"Animals",
"Antibodies, Monoclonal",
"Antigen-Antibody Reactions",
"Antiviral Agents",
"CHO Cells",
"Cricetinae",
"Cricetulus",
"Drug Resistance, Multiple, Viral",
"Enzyme-Linked Immunosorbent Assay",
"Epitope Mapping",
"Gene Expression Regulation, Enzymologic",
"Gene Expression Regulation, Viral",
"Gene Products, pol",
"Guanine",
"Hepatitis B Antibodies",
"Hepatitis B Surface Antigens",
"Hepatitis B virus",
"Humans",
"Immunodominant Epitopes",
"Lamivudine",
"Mutagenesis, Site-Directed",
"Mutation",
"Organophosphonates",
"Transfection"
]
} | Mutations associated with resistance to nucleos(t)ide analogue therapy, singly or in combination with each other or antibody escape-associated mutations, alter HBsAg immunoreactivity through concomitant amino acid substitutions at codons within and downstream of the a determinant. The findings have implications for understanding the native structure of HBsAg, optimizing treatment of chronic hepatitis B and evaluating the success of immunization programmes. | yes | [
{
"from": "human",
"value": "Question: Do antiviral resistance mutations potentiate hepatitis B virus immune evasion through disruption of its surface antigen a determinant?\nContext: {'contexts': ['The hepatitis B virus (HBV) pol gene overlaps the S gene encoding surface antigen (HBsAg). It has been reported previously that drug-induced changes in HBsAg alter its binding to sera from humans immunized against HBV. We investigate here the changes to specific epitopes in the a determinant (the major target of neutralizing antibody) caused by a number of drug-resistant mutations.', 'Recombinant HBsAgs, produced by transfection of Chinese hamster ovary cells with S gene plasmids into which lamivudine, adefovir and entecavir resistance and common antibody-escape mutations had been introduced, were probed with monoclonal antibodies to epitopes in the first and second loops of the a determinant.', 'The mutations rtF166L/sF158Y (lamivudine-associated, compensatory) and rtl169T/sF161L (entecavir-associated, primary) acting alone, and the mutations rtV173L/sE164D (lamivudine-associated, compensatory) and rtSilent/sD144E (antibody escape-associated) each when combined with rtM204V/sl195M (lamivudine-associated, primary) led to decreases in antibody reactivity to epitopes in the first or second loop, or in both loops. The rtM204V/sl195M + rtV173L/sE164D mutations yielded an epitope-antibody profile similar to the rtR153Q/sG145R vaccine escape mutant. The rtM204V/sl195M mutation combined with the rtF166L/sF158Y or rtR153Q/sG145R mutation restored reactivity to second-loop epitopes previously abrogated by single mutations.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adenine', 'Animals', 'Antibodies, Monoclonal', 'Antigen-Antibody Reactions', 'Antiviral Agents', 'CHO Cells', 'Cricetinae', 'Cricetulus', 'Drug Resistance, Multiple, Viral', 'Enzyme-Linked Immunosorbent Assay', 'Epitope Mapping', 'Gene Expression Regulation, Enzymologic', 'Gene Expression Regulation, Viral', 'Gene Products, pol', 'Guanine', 'Hepatitis B Antibodies', 'Hepatitis B Surface Antigens', 'Hepatitis B virus', 'Humans', 'Immunodominant Epitopes', 'Lamivudine', 'Mutagenesis, Site-Directed', 'Mutation', 'Organophosphonates', 'Transfection']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,558,092 | Does transcription factor foxq1 control mucin gene expression and granule content in mouse stomach surface mucous cells? | {
"contexts": [
"The gastric mucosa provides a stringent epithelial barrier and produces acid and enzymes that initiate digestion. In this regenerating tissue, progenitors differentiate continually into 4 principal specialized cell types, yet underlying mechanisms of differentiation are poorly understood. We identified stomach-restricted expression of the forkhead transcription factor FOXQ1.",
"We used a combination of genetic, histochemical, ultrastructural, and molecular analysis to study gastric cell lineages with respect to FOXQ1.",
"Within the developing and adult gastrointestinal tract, Foxq1 messenger RNA (mRNA) is restricted to the stomach and expressed predominantly in foveolar (pit) cells, the abundant mucin-producing cells that line the mucosal surface. Mice carrying Foxq1 coding mutations show virtual absence of mRNA and protein for the backbone of the major stomach mucin MUC5AC. These observations correspond to a paucity of foveolar cell secretory vesicles and notable loss of stomach but not intestinal mucus. Transcriptional profiling identified a surprisingly restricted set of genes with altered expression in Foxq1 mutant stomachs. MUC5AC is a highly tissue-restricted product that similarly depends on FOXQ1 in its other major site of expression, conjunctival goblet cells."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Base Sequence",
"Cell Differentiation",
"Cell Lineage",
"Conjunctiva",
"Epithelial Cells",
"Forkhead Transcription Factors",
"Gastric Mucosa",
"Gene Expression Profiling",
"Gene Expression Regulation",
"Mice",
"Mice, Inbred C57BL",
"Mice, Mutant Strains",
"Molecular Sequence Data",
"Mucin 5AC",
"Mucins",
"Mutation",
"RNA, Messenger",
"Secretory Vesicles",
"Transcription, Genetic",
"Ultrasonography"
]
} | Taken together, these observations imply that promotion of gastric MUC5AC synthesis is a primary, cell-autonomous function of FOXQ1. This study is the first to implicate a transcription factor in terminal differentiation of foveolar cells and begins to define the requirements to assemble highly specialized organelles and cells in the gastric mucosa. | yes | [
{
"from": "human",
"value": "Question: Does transcription factor foxq1 control mucin gene expression and granule content in mouse stomach surface mucous cells?\nContext: {'contexts': ['The gastric mucosa provides a stringent epithelial barrier and produces acid and enzymes that initiate digestion. In this regenerating tissue, progenitors differentiate continually into 4 principal specialized cell types, yet underlying mechanisms of differentiation are poorly understood. We identified stomach-restricted expression of the forkhead transcription factor FOXQ1.', 'We used a combination of genetic, histochemical, ultrastructural, and molecular analysis to study gastric cell lineages with respect to FOXQ1.', 'Within the developing and adult gastrointestinal tract, Foxq1 messenger RNA (mRNA) is restricted to the stomach and expressed predominantly in foveolar (pit) cells, the abundant mucin-producing cells that line the mucosal surface. Mice carrying Foxq1 coding mutations show virtual absence of mRNA and protein for the backbone of the major stomach mucin MUC5AC. These observations correspond to a paucity of foveolar cell secretory vesicles and notable loss of stomach but not intestinal mucus. Transcriptional profiling identified a surprisingly restricted set of genes with altered expression in Foxq1 mutant stomachs. MUC5AC is a highly tissue-restricted product that similarly depends on FOXQ1 in its other major site of expression, conjunctival goblet cells.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Base Sequence', 'Cell Differentiation', 'Cell Lineage', 'Conjunctiva', 'Epithelial Cells', 'Forkhead Transcription Factors', 'Gastric Mucosa', 'Gene Expression Profiling', 'Gene Expression Regulation', 'Mice', 'Mice, Inbred C57BL', 'Mice, Mutant Strains', 'Molecular Sequence Data', 'Mucin 5AC', 'Mucins', 'Mutation', 'RNA, Messenger', 'Secretory Vesicles', 'Transcription, Genetic', 'Ultrasonography']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,556,963 | Does growth hormone ( GH ) treatment restore endothelial function in children with GH deficiency? | {
"contexts": [
"In adults with growth hormone (GH) deficiency (GHD), GH treatment restores impaired endothelial function, a precursor of cardiovascular disease. Its effect in children with GHD is unknown.",
"Three months of GH (0.3 mg/kg/wk) were given to nine children with GHD. Endothelial function was measured via reactive hyperemic response. Forearm blood flow (FBF, strain gauge plethysmography) was measured before and after 5 min of upper arm arterial occlusion. Blood pressure and lipid, insulin and glucose levels were measured. Pretreatment endothelial function was compared to 18 previously studied control children.",
"Percent fall in forearm vascular resistance was greater in controls (81.2 +/- 1.9%) than in children with GHD (69.6 +/- 5.3%, p = 0.021) but was not affected by GH (60.6 +/- 7.5%). GH markedly increased HOMAIR (21 +/- 7 versus 43 +/- 8, p = 0.004). Plasma lipid levels did not significantly differ."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Blood Flow Velocity",
"Blood Pressure",
"Child",
"Deficiency Diseases",
"Endothelium, Vascular",
"Female",
"Forearm",
"Hormone Replacement Therapy",
"Human Growth Hormone",
"Humans",
"Male"
]
} | These results indicate that endothelial function is impaired in children with GHD. GH therapy does not restore the impairment. | no | [
{
"from": "human",
"value": "Question: Does growth hormone ( GH ) treatment restore endothelial function in children with GH deficiency?\nContext: {'contexts': ['In adults with growth hormone (GH) deficiency (GHD), GH treatment restores impaired endothelial function, a precursor of cardiovascular disease. Its effect in children with GHD is unknown.', 'Three months of GH (0.3 mg/kg/wk) were given to nine children with GHD. Endothelial function was measured via reactive hyperemic response. Forearm blood flow (FBF, strain gauge plethysmography) was measured before and after 5 min of upper arm arterial occlusion. Blood pressure and lipid, insulin and glucose levels were measured. Pretreatment endothelial function was compared to 18 previously studied control children.', 'Percent fall in forearm vascular resistance was greater in controls (81.2 +/- 1.9%) than in children with GHD (69.6 +/- 5.3%, p = 0.021) but was not affected by GH (60.6 +/- 7.5%). GH markedly increased HOMAIR (21 +/- 7 versus 43 +/- 8, p = 0.004). Plasma lipid levels did not significantly differ.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Blood Flow Velocity', 'Blood Pressure', 'Child', 'Deficiency Diseases', 'Endothelium, Vascular', 'Female', 'Forearm', 'Hormone Replacement Therapy', 'Human Growth Hormone', 'Humans', 'Male']}"
},
{
"from": "gpt",
"value": "Answer: no"
}
]
|
18,556,142 | Is dose escalation of gemcitabine possible with concurrent chest three-dimensional rather than two-dimensional radiotherapy : a phase I trial in patients with stage III non-small-cell lung cancer? | {
"contexts": [
"To determine in a Phase I study the maximum tolerated dose of weekly gemcitabine concurrent with radiotherapy in locally advanced non-small-cell lung cancer (NSCLC), as well as the relationship between the volume of the esophagus irradiated and severe esophagitis.",
"Twenty-one patients with Stage III NSCLC received gemcitabine initially at 150 mg/m(2)/wk over 7 weeks concurrently with chest radiotherapy to 63 Gy in 34 fractions. The first 9 patients underwent treatment with two-dimensional (2D) radiotherapy; the remaining 12 patients, with three-dimensional conformal radiotherapy (3D-CRT) and target volume reduced to clinically apparent disease. Consolidation was 4 cycles of gemcitabine at 1000 mg/m(2)/wk and cisplatin 60 mg/m(2).",
"In the 2D group, the dose-limiting toxicity, Grade 3 esophagitis, occurred in 3 of 6 patients in the 150-mg/m(2)/wk cohort and 2 of 3 patients in the 125-mg/m(2)/wk cohort. No cases of Grade 3 esophagitis occurred at these doses in the 3D group. At gemcitabine 190 mg/m(2)/wk, 2 of 6 patients in the 3D cohort had Grade 3 esophagitis. The mean percentages of esophagus irradiated to 60 Gy were 68% in the 2D cohort and 18% in the 3D cohort."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Abdomen",
"Adult",
"Aged",
"Aged, 80 and over",
"Antimetabolites, Antineoplastic",
"Carcinoma, Non-Small-Cell Lung",
"Combined Modality Therapy",
"Deoxycytidine",
"Dose-Response Relationship, Drug",
"Dose-Response Relationship, Radiation",
"Feasibility Studies",
"Female",
"Humans",
"Lung Neoplasms",
"Male",
"Middle Aged",
"Radiation-Sensitizing Agents",
"Radiotherapy, Conformal",
"Treatment Outcome"
]
} | We could not escalate the dose of gemcitabine with concurrent radiotherapy when using 2D planning because of severe acute esophagitis. However, we could escalate the dose of gemcitabine to 190 mg/m(2)/wk when using 3D planning. The Phase II dose is 150 mg/m(2)/wk. Three-dimensional CRT permitted the use of higher doses of gemcitabine. | yes | [
{
"from": "human",
"value": "Question: Is dose escalation of gemcitabine possible with concurrent chest three-dimensional rather than two-dimensional radiotherapy : a phase I trial in patients with stage III non-small-cell lung cancer?\nContext: {'contexts': ['To determine in a Phase I study the maximum tolerated dose of weekly gemcitabine concurrent with radiotherapy in locally advanced non-small-cell lung cancer (NSCLC), as well as the relationship between the volume of the esophagus irradiated and severe esophagitis.', 'Twenty-one patients with Stage III NSCLC received gemcitabine initially at 150 mg/m(2)/wk over 7 weeks concurrently with chest radiotherapy to 63 Gy in 34 fractions. The first 9 patients underwent treatment with two-dimensional (2D) radiotherapy; the remaining 12 patients, with three-dimensional conformal radiotherapy (3D-CRT) and target volume reduced to clinically apparent disease. Consolidation was 4 cycles of gemcitabine at 1000 mg/m(2)/wk and cisplatin 60 mg/m(2).', 'In the 2D group, the dose-limiting toxicity, Grade 3 esophagitis, occurred in 3 of 6 patients in the 150-mg/m(2)/wk cohort and 2 of 3 patients in the 125-mg/m(2)/wk cohort. No cases of Grade 3 esophagitis occurred at these doses in the 3D group. At gemcitabine 190 mg/m(2)/wk, 2 of 6 patients in the 3D cohort had Grade 3 esophagitis. The mean percentages of esophagus irradiated to 60 Gy were 68% in the 2D cohort and 18% in the 3D cohort.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Abdomen', 'Adult', 'Aged', 'Aged, 80 and over', 'Antimetabolites, Antineoplastic', 'Carcinoma, Non-Small-Cell Lung', 'Combined Modality Therapy', 'Deoxycytidine', 'Dose-Response Relationship, Drug', 'Dose-Response Relationship, Radiation', 'Feasibility Studies', 'Female', 'Humans', 'Lung Neoplasms', 'Male', 'Middle Aged', 'Radiation-Sensitizing Agents', 'Radiotherapy, Conformal', 'Treatment Outcome']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,556,146 | Do impulsive suicide attempts predict post-treatment relapse in alcohol-dependent patients? | {
"contexts": [
"The present study was designed to examine the influence of suicidality on relapse in alcohol-dependent patients. Specifically, a lifetime suicide attempt at baseline was used to predict relapse in the year after treatment. Also, the unique contribution of impulsive suicide attempts was examined.",
"A total of 154 patients with alcohol dependence, consecutively admitted to four addiction treatment facilities in Warsaw, Poland participated in the study. Of the 154 eligible patients, 118 (76.6%) completed a standardized follow-up assessment at 12 months.",
"Previous suicide attempts were common in adults treated for alcohol dependence with 43% patients in the present sample reporting an attempt at some point during their lifetime. Additionally, more than 62% of those with a lifetime suicide attempt reported making an impulsive attempt. Lifetime suicide attempts were not associated with post-treatment relapse (chi-square=2.37, d.f.=1, p=0.124). However, impulsive suicide attempts strongly predicted relapse (OR=2.81, 95% CI=1.13-6.95, p=0.026) and time to relapse (OR=2.10, 95% CI=1.18-3.74, p=0.012) even after adjusting for other measures of baseline psychopathology, depression, impulsivity, hopelessness and alcohol use severity."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Alcoholism",
"Catchment Area (Health)",
"Female",
"Follow-Up Studies",
"Humans",
"Impulsive Behavior",
"Male",
"Mental Health Services",
"Poland",
"Prospective Studies",
"Recurrence",
"Suicide, Attempted"
]
} | This study is the first to document the relationship between pre-treatment impulsive suicide attempts and higher likelihood of post-treatment relapse in alcohol-dependent patents. Clinicians should routinely conduct an assessment for previous suicide attempts in patients with alcohol use disorders, and when impulsive suicidality is reported, they should recognize the increased risk for relapse and formulate their patients' treatment plans accordingly with the goals of reducing both alcoholic relapse and suicide rates. | yes | [
{
"from": "human",
"value": "Question: Do impulsive suicide attempts predict post-treatment relapse in alcohol-dependent patients?\nContext: {'contexts': ['The present study was designed to examine the influence of suicidality on relapse in alcohol-dependent patients. Specifically, a lifetime suicide attempt at baseline was used to predict relapse in the year after treatment. Also, the unique contribution of impulsive suicide attempts was examined.', 'A total of 154 patients with alcohol dependence, consecutively admitted to four addiction treatment facilities in Warsaw, Poland participated in the study. Of the 154 eligible patients, 118 (76.6%) completed a standardized follow-up assessment at 12 months.', 'Previous suicide attempts were common in adults treated for alcohol dependence with 43% patients in the present sample reporting an attempt at some point during their lifetime. Additionally, more than 62% of those with a lifetime suicide attempt reported making an impulsive attempt. Lifetime suicide attempts were not associated with post-treatment relapse (chi-square=2.37, d.f.=1, p=0.124). However, impulsive suicide attempts strongly predicted relapse (OR=2.81, 95% CI=1.13-6.95, p=0.026) and time to relapse (OR=2.10, 95% CI=1.18-3.74, p=0.012) even after adjusting for other measures of baseline psychopathology, depression, impulsivity, hopelessness and alcohol use severity.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Alcoholism', 'Catchment Area (Health)', 'Female', 'Follow-Up Studies', 'Humans', 'Impulsive Behavior', 'Male', 'Mental Health Services', 'Poland', 'Prospective Studies', 'Recurrence', 'Suicide, Attempted']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,565,284 | Does tetrahydrocurcumin inhibit HT1080 cell migration and invasion via downregulation of MMPs and uPA? | {
"contexts": [
"Tetrahydrocurcumin (THC) is an active metabolite of curcumin. It has been reported to have similar pharmacological activity to curcumin. The proteases that participate in extracellular matrix (ECM) degradation are involved in cancer cell metastasis. The present study investigates the effect of an ultimate metabolite of curcumin, THC, on the invasion and motility of highly-metastatic HT1080 human fibrosarcoma cells.",
"The effect of THC on HT1080 cell invasion and migration was determined using Boyden chamber assay. Cell-adhesion assay was used for examining the binding of cells to ECM molecules. Zymography assay was used to analyze the effect of THC on matrix metalloproteinase (MMP)-2, MMP-9, and urokinase plasminogen activator (uPA) secretion from HT1080 cells. Tissue inhibitor of metalloproteinase (TIMP)-2 and membrane-type 1 matrix metalloproteinase (MT1-MMP) proteins levels were analyzed by Western blotting.",
"Treatment with THC reduced HT1080 cell invasion and migration in a dose-dependent manner. THC also decreased the cell adhesion to Matrigel and laminin-coated plates. Analysis by zymography demonstrated that treatment with THC reduced the levels of MMP-2, MMP-9, and uPA. THC also inhibited the levels of MT1-MMP and TIMP-2 proteins detected by Western blot analysis."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Anticarcinogenic Agents",
"Cell Line, Tumor",
"Cell Movement",
"Curcumin",
"Down-Regulation",
"Humans",
"Matrix Metalloproteinases",
"Mice",
"NIH 3T3 Cells",
"Neoplasm Invasiveness",
"Urokinase-Type Plasminogen Activator"
]
} | Our findings revealed that THC reduced HT1080 cell invasion and migration. The inhibition of cancer cell invasion is associated with the downregulation of ECM degradation enzymes and the inhibition of cell adhesion to ECM proteins. | yes | [
{
"from": "human",
"value": "Question: Does tetrahydrocurcumin inhibit HT1080 cell migration and invasion via downregulation of MMPs and uPA?\nContext: {'contexts': ['Tetrahydrocurcumin (THC) is an active metabolite of curcumin. It has been reported to have similar pharmacological activity to curcumin. The proteases that participate in extracellular matrix (ECM) degradation are involved in cancer cell metastasis. The present study investigates the effect of an ultimate metabolite of curcumin, THC, on the invasion and motility of highly-metastatic HT1080 human fibrosarcoma cells.', 'The effect of THC on HT1080 cell invasion and migration was determined using Boyden chamber assay. Cell-adhesion assay was used for examining the binding of cells to ECM molecules. Zymography assay was used to analyze the effect of THC on matrix metalloproteinase (MMP)-2, MMP-9, and urokinase plasminogen activator (uPA) secretion from HT1080 cells. Tissue inhibitor of metalloproteinase (TIMP)-2 and membrane-type 1 matrix metalloproteinase (MT1-MMP) proteins levels were analyzed by Western blotting.', 'Treatment with THC reduced HT1080 cell invasion and migration in a dose-dependent manner. THC also decreased the cell adhesion to Matrigel and laminin-coated plates. Analysis by zymography demonstrated that treatment with THC reduced the levels of MMP-2, MMP-9, and uPA. THC also inhibited the levels of MT1-MMP and TIMP-2 proteins detected by Western blot analysis.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Anticarcinogenic Agents', 'Cell Line, Tumor', 'Cell Movement', 'Curcumin', 'Down-Regulation', 'Humans', 'Matrix Metalloproteinases', 'Mice', 'NIH 3T3 Cells', 'Neoplasm Invasiveness', 'Urokinase-Type Plasminogen Activator']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,568,338 | Does the reversal of amphetamine-induced locomotor activation by a selective neurotensin-1 receptor agonist exhibit tolerance? | {
"contexts": [
"Neurotensin-1 (NT1) receptor agonists have been proposed as putative antipsychotic drugs. Recently, brain-penetrating NT analogs produced by stability-enhancing modification of the smallest NT fragment, NT(8-13), have demonstrated antipsychotic-like efficacy after acute systemic injection in several preclinical animal tests predictive for antipsychotic efficacy. However, the evidence regarding the persistence versus tolerance of these effects after repeated administration is ambiguous. Previous studies have used compounds that nonselectively activated both NT1 and NT2 receptors or used continuous slow, central infusion of doses rather than daily acute administration, both factors which may have contributed to the ambiguity in the literature regarding the emergence of tolerance.",
"To determine if tolerance develops to the antipsychotic-like effects of NT1 receptor agonists, we investigated the effects of subchronic daily systemic administration of PD149163, a brain-penetrating NT analog with selectivity for the NT1 receptor, on amphetamine-induced locomotor activation, a classic preclinical test of antipsychotic efficacy.",
"Sprague-Dawley rats were pretreated with eight consecutive daily subcutaneous (SC) injections of PD149163 or saline. On the ninth day, rats received a pair of SC injections consisting of PD149163 or saline, followed by amphetamine (0.5 mg/kg) or saline. Locomotor activity was then measured in photobeam-equipped cages.",
"The results indicated that repeated daily administration of PD149163 was able to antagonize amphetamine's locomotor-activating effect comparable to that of the first dose, despite that repeated administration of PD149163 produced an increase in baseline locomotor activity not seen after the first dose."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Amphetamine",
"Animals",
"Antipsychotic Agents",
"Central Nervous System Stimulants",
"Drug Tolerance",
"Injections, Subcutaneous",
"Male",
"Motor Activity",
"Neurotensin",
"Rats",
"Rats, Sprague-Dawley",
"Receptors, Neurotensin"
]
} | The results do not support the development of tolerance for the acute antipsychotic-like effect of NT1 agonists and thus lend support to the contention that NT1 agonists are viable candidates as putative novel antipsychotic drugs. | no | [
{
"from": "human",
"value": "Question: Does the reversal of amphetamine-induced locomotor activation by a selective neurotensin-1 receptor agonist exhibit tolerance?\nContext: {'contexts': ['Neurotensin-1 (NT1) receptor agonists have been proposed as putative antipsychotic drugs. Recently, brain-penetrating NT analogs produced by stability-enhancing modification of the smallest NT fragment, NT(8-13), have demonstrated antipsychotic-like efficacy after acute systemic injection in several preclinical animal tests predictive for antipsychotic efficacy. However, the evidence regarding the persistence versus tolerance of these effects after repeated administration is ambiguous. Previous studies have used compounds that nonselectively activated both NT1 and NT2 receptors or used continuous slow, central infusion of doses rather than daily acute administration, both factors which may have contributed to the ambiguity in the literature regarding the emergence of tolerance.', 'To determine if tolerance develops to the antipsychotic-like effects of NT1 receptor agonists, we investigated the effects of subchronic daily systemic administration of PD149163, a brain-penetrating NT analog with selectivity for the NT1 receptor, on amphetamine-induced locomotor activation, a classic preclinical test of antipsychotic efficacy.', 'Sprague-Dawley rats were pretreated with eight consecutive daily subcutaneous (SC) injections of PD149163 or saline. On the ninth day, rats received a pair of SC injections consisting of PD149163 or saline, followed by amphetamine (0.5 mg/kg) or saline. Locomotor activity was then measured in photobeam-equipped cages.', \"The results indicated that repeated daily administration of PD149163 was able to antagonize amphetamine's locomotor-activating effect comparable to that of the first dose, despite that repeated administration of PD149163 produced an increase in baseline locomotor activity not seen after the first dose.\"], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Amphetamine', 'Animals', 'Antipsychotic Agents', 'Central Nervous System Stimulants', 'Drug Tolerance', 'Injections, Subcutaneous', 'Male', 'Motor Activity', 'Neurotensin', 'Rats', 'Rats, Sprague-Dawley', 'Receptors, Neurotensin']}"
},
{
"from": "gpt",
"value": "Answer: no"
}
]
|
18,542,930 | Does acute tryptophan depletion dose dependently impair object memory in serotonin transporter knockout rats? | {
"contexts": [
"Acute tryptophan depletion (ATD) transiently lowers central serotonin levels and can induce depressive mood states and cognitive defects. Previous studies have shown that ATD impairs object recognition in rats.",
"As individual differences exist in central serotonin neurotransmission, the impact of ATD may vary accordingly. In this experiment, we investigated the hypothesis that male serotonin transporter knockout (SERT(-/-)), rats marked by a lower SERT function, are more vulnerable to the effects of ATD in an object recognition task than male wildtype (SERT(+/+)) and heterozygous (SERT(+/-)) rats.",
"Twelve male SERT(+/+), SERT(+/-), and SERT(-/-) rats were treated with standard dose and low-dose ATD using a gelatine-based protein-carbohydrate mixture lacking tryptophan. In the control treatment, L: -tryptophan was added to the mixture. Four hours after treatment, the rats were subjected to the object recognition task. In addition, the effects of ATD on plasma amino acid concentrations were measured, and concentrations of 5-HT and 5-HIAA were measured in the frontal cortex and hippocampus of these rats.",
"Plasma TRP levels and central 5-HT and 5-HIAA levels were decreased in all genotypes after ATD, but effects were stronger in SERT(-/-) rats. The standard dose of ATD impaired object recognition in all genotypes. SERT(-/-) and SERT(+/-) rats were more vulnerable to low dose of ATD in the object recognition task compared to SERT(+/+) rats."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Amino Acids",
"Animals",
"Dose-Response Relationship, Drug",
"Frontal Lobe",
"Gene Knockout Techniques",
"Genotype",
"Hippocampus",
"Hydroxyindoleacetic Acid",
"Male",
"Memory Disorders",
"Rats",
"Recognition (Psychology)",
"Serotonin",
"Serotonin Plasma Membrane Transport Proteins",
"Tryptophan"
]
} | These results indicate a greater sensitivity to ATD in SERT(-/-) and SERT(+/-) rats, which may be related to stronger central depletion effects in these rats. | yes | [
{
"from": "human",
"value": "Question: Does acute tryptophan depletion dose dependently impair object memory in serotonin transporter knockout rats?\nContext: {'contexts': ['Acute tryptophan depletion (ATD) transiently lowers central serotonin levels and can induce depressive mood states and cognitive defects. Previous studies have shown that ATD impairs object recognition in rats.', 'As individual differences exist in central serotonin neurotransmission, the impact of ATD may vary accordingly. In this experiment, we investigated the hypothesis that male serotonin transporter knockout (SERT(-/-)), rats marked by a lower SERT function, are more vulnerable to the effects of ATD in an object recognition task than male wildtype (SERT(+/+)) and heterozygous (SERT(+/-)) rats.', 'Twelve male SERT(+/+), SERT(+/-), and SERT(-/-) rats were treated with standard dose and low-dose ATD using a gelatine-based protein-carbohydrate mixture lacking tryptophan. In the control treatment, L: -tryptophan was added to the mixture. Four hours after treatment, the rats were subjected to the object recognition task. In addition, the effects of ATD on plasma amino acid concentrations were measured, and concentrations of 5-HT and 5-HIAA were measured in the frontal cortex and hippocampus of these rats.', 'Plasma TRP levels and central 5-HT and 5-HIAA levels were decreased in all genotypes after ATD, but effects were stronger in SERT(-/-) rats. The standard dose of ATD impaired object recognition in all genotypes. SERT(-/-) and SERT(+/-) rats were more vulnerable to low dose of ATD in the object recognition task compared to SERT(+/+) rats.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Amino Acids', 'Animals', 'Dose-Response Relationship, Drug', 'Frontal Lobe', 'Gene Knockout Techniques', 'Genotype', 'Hippocampus', 'Hydroxyindoleacetic Acid', 'Male', 'Memory Disorders', 'Rats', 'Recognition (Psychology)', 'Serotonin', 'Serotonin Plasma Membrane Transport Proteins', 'Tryptophan']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,563,787 | Are postoperative medical complications the main cause of early death after emergency surgery for colonic cancer? | {
"contexts": [
"Only a few small studies have evaluated risk factors related to early death following emergency surgery for colonic cancer. The aim of this study was to identify risk factors for death within 30 days after such surgery.",
"Some 2157 patients who underwent emergency treatment for colonic cancer from May 2001 to December 2005 were identified from the national colorectal cancer registry. Thirty-day mortality rates were calculated and risk factors for early death were identified using logistic regression analysis.",
"The overall 30-day mortality rate was 22.1 per cent. The strongest risk factor for early death was postoperative medical complications (cardiopulmonary, renal, thromboembolic and infectious), with an odds ratio of 11.7 (95 per cent confidence interval 8.8 to 15.5). Such complications occurred in 24.4 per cent of patients, of whom 57.8 per cent died. Other independent risk factors were age at least 71 years, male sex, American Society of Anesthesiologists grade III or more, palliative outcome, tumour perforation, splenectomy and adverse intraoperative surgical events. Postoperative surgical complications were noted in 20.4 per cent of the patients but had no statistically significant influence on mortality."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Adult",
"Age Factors",
"Aged",
"Aged, 80 and over",
"Cause of Death",
"Colectomy",
"Colonic Neoplasms",
"Denmark",
"Emergencies",
"Emergency Treatment",
"Female",
"Humans",
"Male",
"Middle Aged",
"Multivariate Analysis",
"Postoperative Complications",
"Registries",
"Risk Factors",
"Sex Factors",
"Treatment Outcome"
]
} | Emergency surgery for colonic cancer is still associated with an increased risk of death. There is a need for a system providing increased safety in the perioperative period. | yes | [
{
"from": "human",
"value": "Question: Are postoperative medical complications the main cause of early death after emergency surgery for colonic cancer?\nContext: {'contexts': ['Only a few small studies have evaluated risk factors related to early death following emergency surgery for colonic cancer. The aim of this study was to identify risk factors for death within 30 days after such surgery.', 'Some 2157 patients who underwent emergency treatment for colonic cancer from May 2001 to December 2005 were identified from the national colorectal cancer registry. Thirty-day mortality rates were calculated and risk factors for early death were identified using logistic regression analysis.', 'The overall 30-day mortality rate was 22.1 per cent. The strongest risk factor for early death was postoperative medical complications (cardiopulmonary, renal, thromboembolic and infectious), with an odds ratio of 11.7 (95 per cent confidence interval 8.8 to 15.5). Such complications occurred in 24.4 per cent of patients, of whom 57.8 per cent died. Other independent risk factors were age at least 71 years, male sex, American Society of Anesthesiologists grade III or more, palliative outcome, tumour perforation, splenectomy and adverse intraoperative surgical events. Postoperative surgical complications were noted in 20.4 per cent of the patients but had no statistically significant influence on mortality.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Adult', 'Age Factors', 'Aged', 'Aged, 80 and over', 'Cause of Death', 'Colectomy', 'Colonic Neoplasms', 'Denmark', 'Emergencies', 'Emergency Treatment', 'Female', 'Humans', 'Male', 'Middle Aged', 'Multivariate Analysis', 'Postoperative Complications', 'Registries', 'Risk Factors', 'Sex Factors', 'Treatment Outcome']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,549,878 | Is functional restoration of HCV-specific CD8 T cells by PD-1 blockade defined by PD-1 expression and compartmentalization? | {
"contexts": [
"The immunoinhibitory receptor programmed death-1 (PD-1) is up-regulated on dysfunctional virus-specific CD8 T cells during chronic viral infections, and blockade of PD-1/PD-ligand (PD-L) interactions can restore their function. As hepatitis C virus (HCV) persists in the liver with immune-mediated disease pathogenesis, we examined the role of PD-1/PD-L pathway in antigen-specific CD8 T-cell dysfunction in the liver and blood of HCV-infected patients.",
"PD-1 expression and function of circulating CD8 T cells specific for HCV, Epstein-Barr virus, and influenza virus were examined ex vivo and following antigenic stimulation in vitro in patients with acute, chronic, and resolved HCV infection using class I tetramers and flow cytometry. Intrahepatic CD8 T cells were examined from liver explants of chronically HCV-infected transplant recipients.",
"Intrahepatic HCV-specific CD8 T cells from chronically HCV-infected patients were highly PD-1 positive, profoundly dysfunctional, and unexpectedly refractory to PD-1/PD-L blockade, contrasting from circulating PD-1-intermediate HCV-specific CD8 T cells with responsiveness to PD-1/PD-L blockade. This intrahepatic functional impairment was HCV-specific and directly associated with the level of PD-1 expression. Highly PD-1-positive intrahepatic CD8 T cells were more phenotypically exhausted with increased cytotoxic T-lymphocyte antigen 4 and reduced CD28 and CD127 expression, suggesting that active antigen-specific stimulation in the liver induces a profound functional exhaustion not reversible by PD-1/PD-L blockade alone."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Acute Disease",
"Adult",
"Antibodies, Monoclonal",
"Antigens, CD",
"Antiviral Agents",
"Apoptosis Regulatory Proteins",
"B7-H1 Antigen",
"CD28 Antigens",
"CD8-Positive T-Lymphocytes",
"CTLA-4 Antigen",
"Case-Control Studies",
"Cell Compartmentation",
"Cell Proliferation",
"Cells, Cultured",
"Female",
"Flow Cytometry",
"Hepacivirus",
"Hepatitis C",
"Hepatitis C, Chronic",
"Histocompatibility Antigens Class I",
"Humans",
"Interleukin-7 Receptor alpha Subunit",
"Liver",
"Liver Transplantation",
"Lymphocyte Activation",
"Male",
"Middle Aged",
"Pennsylvania",
"Phenotype",
"Programmed Cell Death 1 Receptor"
]
} | HCV-specific CD8 T-cell dysfunction and responsiveness to PD-1/PD-L blockade are defined by their PD-1 expression and compartmentalization. These findings provide new and clinically relevant insight to differential antigen-specific CD8 T-cell exhaustion and their functional restoration. | yes | [
{
"from": "human",
"value": "Question: Is functional restoration of HCV-specific CD8 T cells by PD-1 blockade defined by PD-1 expression and compartmentalization?\nContext: {'contexts': ['The immunoinhibitory receptor programmed death-1 (PD-1) is up-regulated on dysfunctional virus-specific CD8 T cells during chronic viral infections, and blockade of PD-1/PD-ligand (PD-L) interactions can restore their function. As hepatitis C virus (HCV) persists in the liver with immune-mediated disease pathogenesis, we examined the role of PD-1/PD-L pathway in antigen-specific CD8 T-cell dysfunction in the liver and blood of HCV-infected patients.', 'PD-1 expression and function of circulating CD8 T cells specific for HCV, Epstein-Barr virus, and influenza virus were examined ex vivo and following antigenic stimulation in vitro in patients with acute, chronic, and resolved HCV infection using class I tetramers and flow cytometry. Intrahepatic CD8 T cells were examined from liver explants of chronically HCV-infected transplant recipients.', 'Intrahepatic HCV-specific CD8 T cells from chronically HCV-infected patients were highly PD-1 positive, profoundly dysfunctional, and unexpectedly refractory to PD-1/PD-L blockade, contrasting from circulating PD-1-intermediate HCV-specific CD8 T cells with responsiveness to PD-1/PD-L blockade. This intrahepatic functional impairment was HCV-specific and directly associated with the level of PD-1 expression. Highly PD-1-positive intrahepatic CD8 T cells were more phenotypically exhausted with increased cytotoxic T-lymphocyte antigen 4 and reduced CD28 and CD127 expression, suggesting that active antigen-specific stimulation in the liver induces a profound functional exhaustion not reversible by PD-1/PD-L blockade alone.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Acute Disease', 'Adult', 'Antibodies, Monoclonal', 'Antigens, CD', 'Antiviral Agents', 'Apoptosis Regulatory Proteins', 'B7-H1 Antigen', 'CD28 Antigens', 'CD8-Positive T-Lymphocytes', 'CTLA-4 Antigen', 'Case-Control Studies', 'Cell Compartmentation', 'Cell Proliferation', 'Cells, Cultured', 'Female', 'Flow Cytometry', 'Hepacivirus', 'Hepatitis C', 'Hepatitis C, Chronic', 'Histocompatibility Antigens Class I', 'Humans', 'Interleukin-7 Receptor alpha Subunit', 'Liver', 'Liver Transplantation', 'Lymphocyte Activation', 'Male', 'Middle Aged', 'Pennsylvania', 'Phenotype', 'Programmed Cell Death 1 Receptor']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,549,879 | Does a green tea component suppress posttranslational expression of basic fibroblast growth factor in colorectal cancer? | {
"contexts": [
"Green tea catechins are known to have anticarcinogenic effects. Epigallocatechin-3-gallate (EGCG) accounts for almost 50% of the total catechin content in green tea extract and has very potent antioxidant effects. EGCG also inhibits angiogenesis, possibly through the inhibition of proangiogenic factors including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which in turn, inhibits tumor growth and metastasis. However, the exact molecular mechanism by which EGCG suppresses bFGF expression is not known. Our objective was to elucidate the molecular mechanisms by which EGCG inhibits bFGF expression in colorectal cancer.",
"We examined posttranslational regulation of bFGF by EGCG in human colorectal cancer cells. We also examined bFGF in intestinal tumor formation of APC(Min/+) mice with and without catechin treatment.",
"The bFGF protein was quickly degraded in the presence of EGCG, but a proteasome inhibitor suppressed this degradation. EGCG was also found to increase ubiquitination of bFGF and trypsin-like activity of the 20S proteasome, thereby resulting in the degradation of bFGF protein. Furthermore, EGCG suppressed tumor formation in APC(Min/+) mice, compared with vehicle-treated mice, in association with reduced bFGF expression."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Acetylcysteine",
"Adenomatous Polyposis Coli",
"Animals",
"Antineoplastic Agents, Phytogenic",
"Camellia sinensis",
"Catechin",
"Cell Transformation, Neoplastic",
"Colorectal Neoplasms",
"Cycloheximide",
"Cysteine Proteinase Inhibitors",
"Disease Models, Animal",
"Dose-Response Relationship, Drug",
"Down-Regulation",
"Fibroblast Growth Factor 2",
"Genes, APC",
"HCT116 Cells",
"HT29 Cells",
"Humans",
"Mice",
"Proteasome Endopeptidase Complex",
"Proteasome Inhibitors",
"Protein Processing, Post-Translational",
"Protein Synthesis Inhibitors",
"Time Factors",
"Transfection"
]
} | The ubiquitin-proteasome degradation pathway contributes significantly to down-regulation of bFGF expression by EGCG. Catechin compounds have fewer adverse effects than chemotherapeutic agents and hence can be used as proof-of-concept in cancer therapeutics to suppress growth and metastasis by targeting proteins such as bFGF. | yes | [
{
"from": "human",
"value": "Question: Does a green tea component suppress posttranslational expression of basic fibroblast growth factor in colorectal cancer?\nContext: {'contexts': ['Green tea catechins are known to have anticarcinogenic effects. Epigallocatechin-3-gallate (EGCG) accounts for almost 50% of the total catechin content in green tea extract and has very potent antioxidant effects. EGCG also inhibits angiogenesis, possibly through the inhibition of proangiogenic factors including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which in turn, inhibits tumor growth and metastasis. However, the exact molecular mechanism by which EGCG suppresses bFGF expression is not known. Our objective was to elucidate the molecular mechanisms by which EGCG inhibits bFGF expression in colorectal cancer.', 'We examined posttranslational regulation of bFGF by EGCG in human colorectal cancer cells. We also examined bFGF in intestinal tumor formation of APC(Min/+) mice with and without catechin treatment.', 'The bFGF protein was quickly degraded in the presence of EGCG, but a proteasome inhibitor suppressed this degradation. EGCG was also found to increase ubiquitination of bFGF and trypsin-like activity of the 20S proteasome, thereby resulting in the degradation of bFGF protein. Furthermore, EGCG suppressed tumor formation in APC(Min/+) mice, compared with vehicle-treated mice, in association with reduced bFGF expression.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Acetylcysteine', 'Adenomatous Polyposis Coli', 'Animals', 'Antineoplastic Agents, Phytogenic', 'Camellia sinensis', 'Catechin', 'Cell Transformation, Neoplastic', 'Colorectal Neoplasms', 'Cycloheximide', 'Cysteine Proteinase Inhibitors', 'Disease Models, Animal', 'Dose-Response Relationship, Drug', 'Down-Regulation', 'Fibroblast Growth Factor 2', 'Genes, APC', 'HCT116 Cells', 'HT29 Cells', 'Humans', 'Mice', 'Proteasome Endopeptidase Complex', 'Proteasome Inhibitors', 'Protein Processing, Post-Translational', 'Protein Synthesis Inhibitors', 'Time Factors', 'Transfection']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,549,877 | Are neither multiple tumors nor portal hypertension surgical contraindications for hepatocellular carcinoma? | {
"contexts": [
"The surgical indications for multiple hepatocellular carcinomas (HCCs) and for HCC with portal hypertension (PHT) remain controversial.",
"We reviewed 434 patients who had undergone an initial resection for HCC and divided them into a multiple (n = 126) or single (n = 308) group according to the number of tumors. We also classified 386 of the patients into a PHT group (n = 136) and a no-PHT (n = 250) group according to whether they had PHT (defined by the presence of esophageal varices or a platelet count of <100,000/microL in association with splenomegaly).",
"Among Child-Pugh class A patients, the overall survival rates in the multiple group were 58% at 5 years, and 56% in the PHT group, which were lower than those in the single group (68%, P = .035) and the no-PHT group (71%, P = .008). Among Child-Pugh class B patients with multiple HCCs, the 5-year overall survival rate was 19%. Multivariate analyses revealed that the presence of multiple tumors was an independent risk factor for postoperative recurrence (relative risk, 1.64; 95% confidence interval, 1.23-2.18; P = .001). A second resection resulted in satisfactory overall survival after the diagnosis of recurrence in the multiple (73% at 3 years) or PHT (73%) groups, as well as in the single (79%) or no PHT (81%) groups."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Adult",
"Aged",
"Aged, 80 and over",
"Carcinoma, Hepatocellular",
"Contraindications",
"Female",
"Follow-Up Studies",
"Hepatectomy",
"Humans",
"Hypertension, Portal",
"Kaplan-Meier Estimate",
"Liver Cirrhosis",
"Liver Neoplasms",
"Male",
"Middle Aged",
"Neoplasm Staging",
"Neoplasms, Multiple Primary",
"Patient Selection",
"Practice Guidelines as Topic",
"Recurrence",
"Reoperation",
"Risk Assessment",
"Risk Factors",
"Severity of Illness Index",
"Time Factors",
"Treatment Outcome"
]
} | Resection can provide survival benefits even for patients with multiple tumors in a background of Child-Pugh class A cirrhosis, as well as in those with PHT. | yes | [
{
"from": "human",
"value": "Question: Are neither multiple tumors nor portal hypertension surgical contraindications for hepatocellular carcinoma?\nContext: {'contexts': ['The surgical indications for multiple hepatocellular carcinomas (HCCs) and for HCC with portal hypertension (PHT) remain controversial.', 'We reviewed 434 patients who had undergone an initial resection for HCC and divided them into a multiple (n = 126) or single (n = 308) group according to the number of tumors. We also classified 386 of the patients into a PHT group (n = 136) and a no-PHT (n = 250) group according to whether they had PHT (defined by the presence of esophageal varices or a platelet count of <100,000/microL in association with splenomegaly).', 'Among Child-Pugh class A patients, the overall survival rates in the multiple group were 58% at 5 years, and 56% in the PHT group, which were lower than those in the single group (68%, P = .035) and the no-PHT group (71%, P = .008). Among Child-Pugh class B patients with multiple HCCs, the 5-year overall survival rate was 19%. Multivariate analyses revealed that the presence of multiple tumors was an independent risk factor for postoperative recurrence (relative risk, 1.64; 95% confidence interval, 1.23-2.18; P = .001). A second resection resulted in satisfactory overall survival after the diagnosis of recurrence in the multiple (73% at 3 years) or PHT (73%) groups, as well as in the single (79%) or no PHT (81%) groups.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Adult', 'Aged', 'Aged, 80 and over', 'Carcinoma, Hepatocellular', 'Contraindications', 'Female', 'Follow-Up Studies', 'Hepatectomy', 'Humans', 'Hypertension, Portal', 'Kaplan-Meier Estimate', 'Liver Cirrhosis', 'Liver Neoplasms', 'Male', 'Middle Aged', 'Neoplasm Staging', 'Neoplasms, Multiple Primary', 'Patient Selection', 'Practice Guidelines as Topic', 'Recurrence', 'Reoperation', 'Risk Assessment', 'Risk Factors', 'Severity of Illness Index', 'Time Factors', 'Treatment Outcome']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,559,571 | Is better life expectancy in women with BRCA2 compared with BRCA1 mutations attributable to lower frequency and later onset of ovarian cancer? | {
"contexts": [
"No formal assessment of life expectancy in women with BRCA1 and BRCA2 mutations in these genes has been reported previously. We have evaluated life expectancy using actuarial analysis and assessed the effect of breast and ovarian cancers on premature death in >1,000 BRCA1/2 carriers.",
"Families with pathogenic mutations in BRCA1 and BRCA2 have been ascertained in a 10-million population region of United Kingdom since 1996. Mutation carriers and their first-degree relatives were used in an analysis of breast and ovarian cancer incidence and mortality as well as to derive and compare an actuarial assessment of life expectancy.",
"Six hundred twelve BRCA1 and 482 BRCA2 female mutation carriers were identified from 482 families. Life expectancy was significantly reduced for BRCA1 carriers compared with BRCA2 (P = 0.0002). This effect was attributable to an increased death rate from ovarian cancer (P = 0.04). Kaplan-Meier analysis revealed a better long-term survival from early-stage ovarian cancer in BRCA2 carriers but no significant differences in deaths from breast cancer or from women presenting with late-stage ovarian cancer. There was no other major contributing cause to death other than breast/ovarian cancer in BRCA1/2 female carriers."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Aged, 80 and over",
"England",
"Female",
"Genes, BRCA1",
"Genes, BRCA2",
"Humans",
"Incidence",
"Life Expectancy",
"Middle Aged",
"Mutation",
"Ovarian Neoplasms",
"Risk Factors"
]
} | Interventions to reduce ovarian cancer incidence are likely to have a greater effect on life expectancy in BRCA1 compared with BRCA2 carriers. | yes | [
{
"from": "human",
"value": "Question: Is better life expectancy in women with BRCA2 compared with BRCA1 mutations attributable to lower frequency and later onset of ovarian cancer?\nContext: {'contexts': ['No formal assessment of life expectancy in women with BRCA1 and BRCA2 mutations in these genes has been reported previously. We have evaluated life expectancy using actuarial analysis and assessed the effect of breast and ovarian cancers on premature death in >1,000 BRCA1/2 carriers.', 'Families with pathogenic mutations in BRCA1 and BRCA2 have been ascertained in a 10-million population region of United Kingdom since 1996. Mutation carriers and their first-degree relatives were used in an analysis of breast and ovarian cancer incidence and mortality as well as to derive and compare an actuarial assessment of life expectancy.', 'Six hundred twelve BRCA1 and 482 BRCA2 female mutation carriers were identified from 482 families. Life expectancy was significantly reduced for BRCA1 carriers compared with BRCA2 (P = 0.0002). This effect was attributable to an increased death rate from ovarian cancer (P = 0.04). Kaplan-Meier analysis revealed a better long-term survival from early-stage ovarian cancer in BRCA2 carriers but no significant differences in deaths from breast cancer or from women presenting with late-stage ovarian cancer. There was no other major contributing cause to death other than breast/ovarian cancer in BRCA1/2 female carriers.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Aged, 80 and over', 'England', 'Female', 'Genes, BRCA1', 'Genes, BRCA2', 'Humans', 'Incidence', 'Life Expectancy', 'Middle Aged', 'Mutation', 'Ovarian Neoplasms', 'Risk Factors']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,544,144 | Does ultrasound-guided supraclavicular vs infraclavicular brachial plexus block in children? | {
"contexts": [
"Supraclavicular brachial plexus blocks are not common in children because of risk of pneumothorax. However, infraclavicular brachial plexus blocks have been described in paediatric patients both with nerve stimulation and ultrasound (US)-guidance. US-guidance reduces the risk of complications in supraclavicular brachial plexus blocks in adults.",
"To compare the success rate, complications and time of performance of US-guided supraclavicular vs infraclavicular brachial plexus blocks in children.",
"Eighty children, 5-15 years old, scheduled for upper limb surgery were divided into two randomized groups: group S (supraclavicular), n = 40, and group I (infraclavicular), n = 40. All blocks performed were exclusively US-guided, by a senior anaesthesiologist with at least 6 months of experience in US-guided blocks. For supraclavicular blocks the probe was placed in coronal-oblique-plane in the supraclavicular fossa and the puncture was in-plane (IP) from lateral to medial. For infraclavicular blocks the probe was placed parallel and below the clavicle and the puncture was out-of-plane. Ropivacaine 0.5% was administered up to a maximum of 0.5 ml x kg(-1) until appropriate US-guided-spread was achieved. Block duration and volumes of ropivacaine used (mean+/-1SD) in the supraclavicular approach were recorded. Success rate (mean +/- 1 SD, 95%confidence interval), complications rate and time to perform the block (two-tailed Student's test) were recorded both for supraclavicular and infraclavicular approaches.",
"In the US-guided supraclavicular brachial plexus blocks, the duration of the sensory block was 6.5 +/- 2 h and of the motor block was 4 +/- 1 h. The volume of ropivacaine used in this group was 6 +/- 2 ml. In group I, 88% of blocks achieved surgical anaesthesia without any supplemental analgesia compared with 95% in group S (P = 0.39; difference=7%; 95% CI: -10% to 24%). Failures in group I were because of arterial puncture and insufficient ulnar or radial sensory block. Failures in group S were because of insufficient ulnar sensory block. No pneumothorax or Horner's syndrome was recorded in either group. The mean time (SD) to perform the block was in group I: 13 min (range 5-16) and in group S: 9 min (range 7-12); the 95% CI for this difference was 2-6 min and was statistically significant (P < 0.05)."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Amides",
"Anesthetics, Local",
"Brachial Plexus",
"Child",
"Child, Preschool",
"Clavicle",
"Electric Stimulation",
"Female",
"Humans",
"Male",
"Nerve Block",
"Postoperative Complications",
"Ropivacaine",
"Time Factors",
"Treatment Outcome",
"Ultrasonography, Interventional"
]
} | (i) Ultrasound-guided supraclavicular and infraclavicular brachial plexus blocks are effective in children. (ii) There has been no pneumothorax in 40 US-guided supraclavicular brachial plexus blocks performed by anaesthesiologists already trained in US-guided regional anaesthesia using an IP technique in children > or =5 years old. (iii) In this study, the supraclavicular approach of the brachial plexus was faster to perform than the infraclavicular one. | yes | [
{
"from": "human",
"value": "Question: Does ultrasound-guided supraclavicular vs infraclavicular brachial plexus block in children?\nContext: {'contexts': ['Supraclavicular brachial plexus blocks are not common in children because of risk of pneumothorax. However, infraclavicular brachial plexus blocks have been described in paediatric patients both with nerve stimulation and ultrasound (US)-guidance. US-guidance reduces the risk of complications in supraclavicular brachial plexus blocks in adults.', 'To compare the success rate, complications and time of performance of US-guided supraclavicular vs infraclavicular brachial plexus blocks in children.', \"Eighty children, 5-15 years old, scheduled for upper limb surgery were divided into two randomized groups: group S (supraclavicular), n = 40, and group I (infraclavicular), n = 40. All blocks performed were exclusively US-guided, by a senior anaesthesiologist with at least 6 months of experience in US-guided blocks. For supraclavicular blocks the probe was placed in coronal-oblique-plane in the supraclavicular fossa and the puncture was in-plane (IP) from lateral to medial. For infraclavicular blocks the probe was placed parallel and below the clavicle and the puncture was out-of-plane. Ropivacaine 0.5% was administered up to a maximum of 0.5 ml x kg(-1) until appropriate US-guided-spread was achieved. Block duration and volumes of ropivacaine used (mean+/-1SD) in the supraclavicular approach were recorded. Success rate (mean +/- 1 SD, 95%confidence interval), complications rate and time to perform the block (two-tailed Student's test) were recorded both for supraclavicular and infraclavicular approaches.\", \"In the US-guided supraclavicular brachial plexus blocks, the duration of the sensory block was 6.5 +/- 2 h and of the motor block was 4 +/- 1 h. The volume of ropivacaine used in this group was 6 +/- 2 ml. In group I, 88% of blocks achieved surgical anaesthesia without any supplemental analgesia compared with 95% in group S (P = 0.39; difference=7%; 95% CI: -10% to 24%). Failures in group I were because of arterial puncture and insufficient ulnar or radial sensory block. Failures in group S were because of insufficient ulnar sensory block. No pneumothorax or Horner's syndrome was recorded in either group. The mean time (SD) to perform the block was in group I: 13 min (range 5-16) and in group S: 9 min (range 7-12); the 95% CI for this difference was 2-6 min and was statistically significant (P < 0.05).\"], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Amides', 'Anesthetics, Local', 'Brachial Plexus', 'Child', 'Child, Preschool', 'Clavicle', 'Electric Stimulation', 'Female', 'Humans', 'Male', 'Nerve Block', 'Postoperative Complications', 'Ropivacaine', 'Time Factors', 'Treatment Outcome', 'Ultrasonography, Interventional']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,564,283 | Does a histopathologic study of arthropod bite reactions in 20 patients highlight relevant adnexal involvement? | {
"contexts": [
"Insect bites produce diverse skin reactions. Although quite common, the histopathologic features of arthropod assaults have not ever been studied systemically.",
"Twenty biopsies from cases, clinically diagnosed as arthropod bite reactions between January 2003 and June 2007 were reviewed retrospectively. The aim of the study was to verify as to whether reliable histopathologic criteria could be established based on the frequency of findings observed.",
"Epidermal spongiosis (present in 16 of 20 cases), in particular spongiosis of the infundibular epithelium and acrosyringia as well as eosinophilic spongiosis, emerge as relevant diagnostic clues. A moderately dense, superficial and deep infiltrate consisting mainly of lymphocytes and eosinophils was prevalent in the dermis, with eosinophils tending to interstitial and periadnexal distribution. Of note, 19 of 20 (95%) cases revealed periadnexal involvement, whereas 16 of 20 (80%) had the infiltrate extending particularly along the sweat ducts and the coiled glands. In three biopsies, concomitant involvement of sweat glands, hair follicles and sebaceous glands was noted."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Hair Follicle",
"Humans",
"Insect Bites and Stings",
"Retrospective Studies",
"Sebaceous Glands",
"Skin Diseases",
"Sweat Glands"
]
} | A practical histopathologic algorithm of arthropod bite recognition is proposed. The involvement of the sweat glands in the pattern of arthropod bite reaction is suggested as a new reliable diagnostic clue. | yes | [
{
"from": "human",
"value": "Question: Does a histopathologic study of arthropod bite reactions in 20 patients highlight relevant adnexal involvement?\nContext: {'contexts': ['Insect bites produce diverse skin reactions. Although quite common, the histopathologic features of arthropod assaults have not ever been studied systemically.', 'Twenty biopsies from cases, clinically diagnosed as arthropod bite reactions between January 2003 and June 2007 were reviewed retrospectively. The aim of the study was to verify as to whether reliable histopathologic criteria could be established based on the frequency of findings observed.', 'Epidermal spongiosis (present in 16 of 20 cases), in particular spongiosis of the infundibular epithelium and acrosyringia as well as eosinophilic spongiosis, emerge as relevant diagnostic clues. A moderately dense, superficial and deep infiltrate consisting mainly of lymphocytes and eosinophils was prevalent in the dermis, with eosinophils tending to interstitial and periadnexal distribution. Of note, 19 of 20 (95%) cases revealed periadnexal involvement, whereas 16 of 20 (80%) had the infiltrate extending particularly along the sweat ducts and the coiled glands. In three biopsies, concomitant involvement of sweat glands, hair follicles and sebaceous glands was noted.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Hair Follicle', 'Humans', 'Insect Bites and Stings', 'Retrospective Studies', 'Sebaceous Glands', 'Skin Diseases', 'Sweat Glands']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,566,467 | Do amyloid-beta deposits lead to retinal degeneration in a mouse model of Alzheimer disease? | {
"contexts": [
"To compare the temporal and spatial expression patterns of amyloid precursor protein (APP), amyloid-beta deposits, inflammatory chemokines, and apoptosis in the retina of a mouse model of Alzheimer disease (AD).",
"Retinas of transgenic mice harboring a mutant presenilin (PS1) and a mutant APP gene were processed for TUNEL and immunohistochemistry with antibodies against APP, amyloid-beta, monocyte chemotactic protein (MCP)-1, and F4/80. Comparisons were made between age groups and between transgenic and wild-type congeners.",
"The neuroretina demonstrated age-dependent increases in APP in the ganglion cells (RGCs) and in neurons of the inner nuclear layer (INL). Amyloid-beta demonstrated significant age-dependent deposition in the nerve fiber layer (NFL). TUNEL-positive RGC increased in an age-dependent fashion and in transgenic compared with wild-type congeners. Concomitant overexpression of MCP-1 and intense immunoreactivity for F4/80 suggested that RGCs upregulate MCP-1 in response to amyloid-beta. Activated microglia proliferated in response to MCP-1. In the outer retina, retinal pigment epithelium (RPE) demonstrated moderate age-dependent APP immunoreactivity, but nearby drusenlike deposits were not present. Amyloid-beta was observed in the choriocapillaris of the older animals."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Alzheimer Disease",
"Amyloid beta-Peptides",
"Animals",
"Antigens, Differentiation",
"Apoptosis",
"Biomarkers",
"Chemokine CCL2",
"Disease Models, Animal",
"Immunohistochemistry",
"In Situ Nick-End Labeling",
"Membrane Glycoproteins",
"Mice",
"Mice, Transgenic",
"Retina",
"Retinal Degeneration"
]
} | Amyloid-beta deposits accumulate with age in the retina of a transgenic mouse model of AD. The amyloid-beta loads are accompanied by increased immunoreactivity for MCP-1, F4/80, and TUNEL-positive profiles in the RGC layer. The results suggest that amyloid-beta causes neurodegeneration in the retina of the doubly mutant transgenic mouse model of AD. | yes | [
{
"from": "human",
"value": "Question: Do amyloid-beta deposits lead to retinal degeneration in a mouse model of Alzheimer disease?\nContext: {'contexts': ['To compare the temporal and spatial expression patterns of amyloid precursor protein (APP), amyloid-beta deposits, inflammatory chemokines, and apoptosis in the retina of a mouse model of Alzheimer disease (AD).', 'Retinas of transgenic mice harboring a mutant presenilin (PS1) and a mutant APP gene were processed for TUNEL and immunohistochemistry with antibodies against APP, amyloid-beta, monocyte chemotactic protein (MCP)-1, and F4/80. Comparisons were made between age groups and between transgenic and wild-type congeners.', 'The neuroretina demonstrated age-dependent increases in APP in the ganglion cells (RGCs) and in neurons of the inner nuclear layer (INL). Amyloid-beta demonstrated significant age-dependent deposition in the nerve fiber layer (NFL). TUNEL-positive RGC increased in an age-dependent fashion and in transgenic compared with wild-type congeners. Concomitant overexpression of MCP-1 and intense immunoreactivity for F4/80 suggested that RGCs upregulate MCP-1 in response to amyloid-beta. Activated microglia proliferated in response to MCP-1. In the outer retina, retinal pigment epithelium (RPE) demonstrated moderate age-dependent APP immunoreactivity, but nearby drusenlike deposits were not present. Amyloid-beta was observed in the choriocapillaris of the older animals.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Alzheimer Disease', 'Amyloid beta-Peptides', 'Animals', 'Antigens, Differentiation', 'Apoptosis', 'Biomarkers', 'Chemokine CCL2', 'Disease Models, Animal', 'Immunohistochemistry', 'In Situ Nick-End Labeling', 'Membrane Glycoproteins', 'Mice', 'Mice, Transgenic', 'Retina', 'Retinal Degeneration']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,558,628 | Does high-mobility group box 1 restore cardiac function after myocardial infarction in transgenic mice? | {
"contexts": [
"High-mobility group box 1 (HMGB1) is a nuclear DNA-binding protein and is released from necrotic cells, inducing inflammatory responses and promoting tissue repair and angiogenesis. To test the hypothesis that HMGB1 enhances angiogenesis and restores cardiac function after myocardial infarction (MI), we generated transgenic mice with cardiac-specific overexpression of HMGB1 (HMGB1-Tg) using alpha-myosin heavy chain promoter.",
"The left anterior descending coronary artery was ligated in HMGB1-Tg and wild-type littermate (Wt) mice. After coronary artery ligation, HMGB1 was released into circulation from the necrotic cardiomyocytes of HMGB1-overexpressing hearts. The size of MI was smaller in HMGB1-Tg than in Wt mice. Echocardiography and cardiac catheterization demonstrated that cardiac remodelling and dysfunction after MI were prevented in HMGB1-Tg mice compared with Wt mice. Furthermore, the survival rate after MI of HMGB1-Tg mice was higher than that of Wt mice. Immunohistochemical staining revealed that capillary and arteriole formation after MI was enhanced in HMGB1-Tg mice."
],
"labels": [
"OBJECTIVE",
"RESULTS"
],
"meshes": [
"Animals",
"Coronary Vessels",
"HMGB1 Protein",
"Heart",
"Ligation",
"Mice",
"Mice, Transgenic",
"Myocardial Infarction",
"Myocardium",
"Myosin Heavy Chains",
"Neovascularization, Physiologic",
"Promoter Regions, Genetic",
"Ventricular Myosins",
"Ventricular Remodeling"
]
} | We report the first in vivo evidence that HMGB1 enhances angiogenesis, restores cardiac function, and improves survival after MI. These results may provide a novel therapeutic approach for left ventricular dysfunction after MI. | yes | [
{
"from": "human",
"value": "Question: Does high-mobility group box 1 restore cardiac function after myocardial infarction in transgenic mice?\nContext: {'contexts': ['High-mobility group box 1 (HMGB1) is a nuclear DNA-binding protein and is released from necrotic cells, inducing inflammatory responses and promoting tissue repair and angiogenesis. To test the hypothesis that HMGB1 enhances angiogenesis and restores cardiac function after myocardial infarction (MI), we generated transgenic mice with cardiac-specific overexpression of HMGB1 (HMGB1-Tg) using alpha-myosin heavy chain promoter.', 'The left anterior descending coronary artery was ligated in HMGB1-Tg and wild-type littermate (Wt) mice. After coronary artery ligation, HMGB1 was released into circulation from the necrotic cardiomyocytes of HMGB1-overexpressing hearts. The size of MI was smaller in HMGB1-Tg than in Wt mice. Echocardiography and cardiac catheterization demonstrated that cardiac remodelling and dysfunction after MI were prevented in HMGB1-Tg mice compared with Wt mice. Furthermore, the survival rate after MI of HMGB1-Tg mice was higher than that of Wt mice. Immunohistochemical staining revealed that capillary and arteriole formation after MI was enhanced in HMGB1-Tg mice.'], 'labels': ['OBJECTIVE', 'RESULTS'], 'meshes': ['Animals', 'Coronary Vessels', 'HMGB1 Protein', 'Heart', 'Ligation', 'Mice', 'Mice, Transgenic', 'Myocardial Infarction', 'Myocardium', 'Myosin Heavy Chains', 'Neovascularization, Physiologic', 'Promoter Regions, Genetic', 'Ventricular Myosins', 'Ventricular Remodeling']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,568,139 | Does the culture site of the gallbladder affect recovery of bacteria in symptomatic cholelithiasis? | {
"contexts": [
"Traditional methods for bile culturing may miss a large number of underlying bacterial infections that could lead to acute or chronic cholecystitis.",
"to evaluate possible differences regarding the site of material collection and thus to detect the most suitable sample site for gallbladder culture.",
"A cohort of 137 patients with symptomatic cholelithiasis was enrolled. After surgical excision of the gallbladder, bile cultures were separately performed from fundus, body and neck. Identification of bacteria as well as computation of mean bacterial concentrations were performed with standard microbiological techniques. Wilcoxon's paired and Chi-square tests were used for comparison between continuous and discrete parameters, respectively.",
"Thirty-one patients (22.6%) demonstrated at least one positive culture sample. Positivity was 31/31 (100.0%) in neck samples, 20/31 (64.5%) in body and 13/31 (41.9%) in fundus samples (P<0.001). The microorganisms identified were Escherichia coli (14 cases) and Enterococcus faecalis (10 cases), followed by Staphylococcus aureus (3 cases), Pseudomonas aeruginosa, Enterococcus faecium, Enterobacter aerogenes and Enterobacter cloacae (1 case each). Mean bacterial concentrations in positive samples derived from the neck (272.2 +/- 187.5) were higher (P<0.01) when compared to those derived from both the body (38.2 +/- 28.7) and the fundus (12.5 +/- 11.3). Mean bacterial concentrations in positive samples derived from the body were higher (P<0.01) than those derived from the fundus."
],
"labels": [
"OBJECTIVE",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Bacteria",
"Bacterial Infections",
"Bile",
"Cholecystectomy, Laparoscopic",
"Cholecystitis",
"Cholelithiasis",
"Colony Count, Microbial",
"Follow-Up Studies",
"Gallbladder",
"Humans"
]
} | The neck of the gallbladder hosts the biggest bacterial load in comparison with the body and the fundus. This difference might be attributed to the presence of Rokitansky-Aschoff sinuses, which is the main histological characteristic of the region. | yes | [
{
"from": "human",
"value": "Question: Does the culture site of the gallbladder affect recovery of bacteria in symptomatic cholelithiasis?\nContext: {'contexts': ['Traditional methods for bile culturing may miss a large number of underlying bacterial infections that could lead to acute or chronic cholecystitis.', 'to evaluate possible differences regarding the site of material collection and thus to detect the most suitable sample site for gallbladder culture.', \"A cohort of 137 patients with symptomatic cholelithiasis was enrolled. After surgical excision of the gallbladder, bile cultures were separately performed from fundus, body and neck. Identification of bacteria as well as computation of mean bacterial concentrations were performed with standard microbiological techniques. Wilcoxon's paired and Chi-square tests were used for comparison between continuous and discrete parameters, respectively.\", 'Thirty-one patients (22.6%) demonstrated at least one positive culture sample. Positivity was 31/31 (100.0%) in neck samples, 20/31 (64.5%) in body and 13/31 (41.9%) in fundus samples (P<0.001). The microorganisms identified were Escherichia coli (14 cases) and Enterococcus faecalis (10 cases), followed by Staphylococcus aureus (3 cases), Pseudomonas aeruginosa, Enterococcus faecium, Enterobacter aerogenes and Enterobacter cloacae (1 case each). Mean bacterial concentrations in positive samples derived from the neck (272.2 +/- 187.5) were higher (P<0.01) when compared to those derived from both the body (38.2 +/- 28.7) and the fundus (12.5 +/- 11.3). Mean bacterial concentrations in positive samples derived from the body were higher (P<0.01) than those derived from the fundus.'], 'labels': ['OBJECTIVE', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Bacteria', 'Bacterial Infections', 'Bile', 'Cholecystectomy, Laparoscopic', 'Cholecystitis', 'Cholelithiasis', 'Colony Count, Microbial', 'Follow-Up Studies', 'Gallbladder', 'Humans']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,558,183 | Does laparoscopic cholecystectomy for biliary dyskinesia in children provide durable symptom relief? | {
"contexts": [
"The purpose of this study was to determine the effectiveness of laparoscopic cholecystectomy in children with biliary dyskinesia.",
"Reports of children with an abnormal cholecystokinin (CCK)-stimulated HIDA scan between January 2001 and July 2006 who underwent laparoscopic cholecystectomy were reviewed. Postoperatively, a 23-item Likert scale, symptom questionnaire was administered to parents.",
"Sixty-four children with chronic abdominal pain and no gallstones on ultrasound had an abnormal CCK-HIDA scan. Twenty-three children (median age, 14 years; 16 girls), with mean (SD) ejection fraction of 17% (8), underwent laparoscopic cholecystectomy and were further analyzed. Preoperatively, these children had right upper quadrant/epigastric pain (78%), nausea (52%), vomiting (43%), and generalized abdominal pain (22%) lasting for a median of 3 months (range, 1 month to 2.5 years). Median postoperative follow-up was 2.7 years. Sixteen (70%) parents completed the questionnaire. Of those who responded, 63% indicated that their children had no abdominal pain, 87% had no vomiting, and 69% had no nausea in the month preceding the questionnaire. Overall, 67% of parents indicated that their children's symptoms were completely relieved after cholecystectomy, whereas 7% indicated that the symptoms were not relieved."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Abdominal Pain",
"Adolescent",
"Biliary Dyskinesia",
"Child",
"Cholecystectomy, Laparoscopic",
"Chronic Disease",
"Female",
"Humans",
"Male",
"Pain Measurement",
"Patient Satisfaction",
"Postoperative Complications",
"Preoperative Care",
"Prognosis",
"Quality of Life",
"Retrospective Studies",
"Risk Assessment",
"Severity of Illness Index",
"Surveys and Questionnaires"
]
} | Laparoscopic cholecystectomy is effective in providing both short-term and long-term improvement of symptoms in children with biliary dyskinesia. | yes | [
{
"from": "human",
"value": "Question: Does laparoscopic cholecystectomy for biliary dyskinesia in children provide durable symptom relief?\nContext: {'contexts': ['The purpose of this study was to determine the effectiveness of laparoscopic cholecystectomy in children with biliary dyskinesia.', 'Reports of children with an abnormal cholecystokinin (CCK)-stimulated HIDA scan between January 2001 and July 2006 who underwent laparoscopic cholecystectomy were reviewed. Postoperatively, a 23-item Likert scale, symptom questionnaire was administered to parents.', \"Sixty-four children with chronic abdominal pain and no gallstones on ultrasound had an abnormal CCK-HIDA scan. Twenty-three children (median age, 14 years; 16 girls), with mean (SD) ejection fraction of 17% (8), underwent laparoscopic cholecystectomy and were further analyzed. Preoperatively, these children had right upper quadrant/epigastric pain (78%), nausea (52%), vomiting (43%), and generalized abdominal pain (22%) lasting for a median of 3 months (range, 1 month to 2.5 years). Median postoperative follow-up was 2.7 years. Sixteen (70%) parents completed the questionnaire. Of those who responded, 63% indicated that their children had no abdominal pain, 87% had no vomiting, and 69% had no nausea in the month preceding the questionnaire. Overall, 67% of parents indicated that their children's symptoms were completely relieved after cholecystectomy, whereas 7% indicated that the symptoms were not relieved.\"], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Abdominal Pain', 'Adolescent', 'Biliary Dyskinesia', 'Child', 'Cholecystectomy, Laparoscopic', 'Chronic Disease', 'Female', 'Humans', 'Male', 'Pain Measurement', 'Patient Satisfaction', 'Postoperative Complications', 'Preoperative Care', 'Prognosis', 'Quality of Life', 'Retrospective Studies', 'Risk Assessment', 'Severity of Illness Index', 'Surveys and Questionnaires']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,554,706 | Does surfactant protein D inhibit TNF-alpha production by macrophages and dendritic cells in mice? | {
"contexts": [
"Surfactant protein (SP) D shares target cells with the proinflammatory cytokine TNF-alpha, an important autocrine stimulator of dendritic cells and macrophages in the airways.",
"We sought to study the mechanisms by which TNF-alpha and SP-D can affect cellular components of the pulmonary innate immune system.",
"Cytokine and SP-D protein and mRNA expression was assessed by means of ELISA, Western blotting, and real-time PCR, respectively, by using in vivo models of allergic airway sensitization. Macrophage and dendritic cell phenotypes were analyzed by means of FACS analysis. Maturation of bone marrow-derived dendritic cells was investigated in vitro.",
"TNF-alpha, elicited either by allergen exposure or pulmonary overexpression, induced SP-D, IL-13, and mononuclear cell influx in the lung. Recombinant IL-13 by itself was also capable of enhancing SP-D in vivo and in vitro, and the SP-D response to allergen challenge was impaired in IL-13-deficient mice. Allergen-induced increase of SP-D in the airways coincided with resolution of TNF-alpha release and cell influx. SP-D-deficient mice had constitutively high numbers of alveolar mononuclear cells expressing TNF-alpha, MHC class II, CD86, and CD11b, characteristics of proinflammatory, myeloid dendritic cells. Recombinant SP-D significantly suppressed all of these molecules in bone marrow-derived dendritic cell cultures."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Dendritic Cells",
"Interleukin-13",
"Lung",
"Macrophages",
"Mice",
"Mice, Inbred BALB C",
"Mice, Inbred C57BL",
"Mice, Knockout",
"Mice, Transgenic",
"Pulmonary Surfactant-Associated Protein D",
"Tumor Necrosis Factor-alpha"
]
} | TNF-alpha can contribute to enhanced SP-D production in the lung indirectly through inducing IL-13. SP-D, on the other hand, can antagonize the proinflammatory effects of TNF-alpha on macrophages and dendritic cells, at least partly, by inhibiting production of this cytokine. | yes | [
{
"from": "human",
"value": "Question: Does surfactant protein D inhibit TNF-alpha production by macrophages and dendritic cells in mice?\nContext: {'contexts': ['Surfactant protein (SP) D shares target cells with the proinflammatory cytokine TNF-alpha, an important autocrine stimulator of dendritic cells and macrophages in the airways.', 'We sought to study the mechanisms by which TNF-alpha and SP-D can affect cellular components of the pulmonary innate immune system.', 'Cytokine and SP-D protein and mRNA expression was assessed by means of ELISA, Western blotting, and real-time PCR, respectively, by using in vivo models of allergic airway sensitization. Macrophage and dendritic cell phenotypes were analyzed by means of FACS analysis. Maturation of bone marrow-derived dendritic cells was investigated in vitro.', 'TNF-alpha, elicited either by allergen exposure or pulmonary overexpression, induced SP-D, IL-13, and mononuclear cell influx in the lung. Recombinant IL-13 by itself was also capable of enhancing SP-D in vivo and in vitro, and the SP-D response to allergen challenge was impaired in IL-13-deficient mice. Allergen-induced increase of SP-D in the airways coincided with resolution of TNF-alpha release and cell influx. SP-D-deficient mice had constitutively high numbers of alveolar mononuclear cells expressing TNF-alpha, MHC class II, CD86, and CD11b, characteristics of proinflammatory, myeloid dendritic cells. Recombinant SP-D significantly suppressed all of these molecules in bone marrow-derived dendritic cell cultures.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Dendritic Cells', 'Interleukin-13', 'Lung', 'Macrophages', 'Mice', 'Mice, Inbred BALB C', 'Mice, Inbred C57BL', 'Mice, Knockout', 'Mice, Transgenic', 'Pulmonary Surfactant-Associated Protein D', 'Tumor Necrosis Factor-alpha']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,573,482 | Is age-related renal disease in female Dahl salt-sensitive rats attenuated with 17 beta-estradiol supplementation by modulating nitric oxide synthase expression? | {
"contexts": [
"The incidence of chronic renal disease in women increases with aging, especially after menopause, suggesting that loss of sex hormones may contribute to the development and progression of renal disease. However, the mechanisms by which sex hormones, particularly estrogens, contribute to the disease process are unclear.",
"The present study examined the effects of ovariectomy (OVX) with or without 17 beta-estradiol (E2) supplementation (OVX+E2) on the expression of inducible (iNOS) and endothelial (eNOS) nitric oxide synthase in the kidney.",
"The study was performed in young (4 months [4M]) and aged (12 months [12M]) female Dahl salt-sensitive rats fed a low-sodium (0.1% NaCl) diet. At 3 months of age, the animals were either subjected to sham surgery, OVX, or OVX with implantation of an E2 silastic pellet. The treatments were administered for either 1 or 9 months, rendering the animals 4 months of age or 12 months of age at the time of sacrifice, respectively. Renal expression of NOS isoforms was measured by Western blotting and immunohistochemistry.",
"OVX in the aged rats was associated with 35% and 25% decreases in medullary iNOS (mean [SEM] relative optical density [ROD]: 4M OVX, 1.81 [0.14] vs 12M OVX, 1.17 [0.16]; P < 0.05) and eNOS (mean ROD: 4M OVX, 1.91 [0.09] vs 12M OVX, 1.43 [0.15]; P < 0.05) protein expression, respectively, and a 25-fold increase in the abundance of CD68-positive cells, indicating macrophage infiltration (mean cells/mm2: 4M OVX, 1.18 [0.09] vs 12M OVX, 30.0 [0.74]; P < 0.001). E2 supplementation either partially or completely attenuated these changes in iNOS (mean ROD: 4M OVX+E2, 2.26 [0.08] vs 12M OVX+E2, 1.70 [0.09]; P < 0.05), eNOS (mean ROD: 4M OVX+E2, 2.03 [0.07] vs 12M OVX+E2, 1.77 [0.11]; P = NS) and CD68 (mean cells/mm2: 4M OVX+E2, 1.46 [0.07] vs 12M OVX+E2, 6.87 [1.6]; P < 0.01) associated with OVX in the aging kidney."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aging",
"Animals",
"Blotting, Western",
"Diet, Sodium-Restricted",
"Disease Models, Animal",
"Down-Regulation",
"Estradiol",
"Female",
"Kidney",
"Kidney Failure, Chronic",
"Nitric Oxide Synthase Type II",
"Nitric Oxide Synthase Type III",
"Postmenopause",
"Rats",
"Rats, Inbred Dahl"
]
} | These data suggest that ovarian E2 loss with aging may contribute to the development of age-related renal disease through downregulation of iNOS and eNOS protein abundance and increased renal inflammation in this animal model. Furthermore, E2 supplementation may be protective in the aging kidney by attenuating these changes. | yes | [
{
"from": "human",
"value": "Question: Is age-related renal disease in female Dahl salt-sensitive rats attenuated with 17 beta-estradiol supplementation by modulating nitric oxide synthase expression?\nContext: {'contexts': ['The incidence of chronic renal disease in women increases with aging, especially after menopause, suggesting that loss of sex hormones may contribute to the development and progression of renal disease. However, the mechanisms by which sex hormones, particularly estrogens, contribute to the disease process are unclear.', 'The present study examined the effects of ovariectomy (OVX) with or without 17 beta-estradiol (E2) supplementation (OVX+E2) on the expression of inducible (iNOS) and endothelial (eNOS) nitric oxide synthase in the kidney.', 'The study was performed in young (4 months [4M]) and aged (12 months [12M]) female Dahl salt-sensitive rats fed a low-sodium (0.1% NaCl) diet. At 3 months of age, the animals were either subjected to sham surgery, OVX, or OVX with implantation of an E2 silastic pellet. The treatments were administered for either 1 or 9 months, rendering the animals 4 months of age or 12 months of age at the time of sacrifice, respectively. Renal expression of NOS isoforms was measured by Western blotting and immunohistochemistry.', 'OVX in the aged rats was associated with 35% and 25% decreases in medullary iNOS (mean [SEM] relative optical density [ROD]: 4M OVX, 1.81 [0.14] vs 12M OVX, 1.17 [0.16]; P < 0.05) and eNOS (mean ROD: 4M OVX, 1.91 [0.09] vs 12M OVX, 1.43 [0.15]; P < 0.05) protein expression, respectively, and a 25-fold increase in the abundance of CD68-positive cells, indicating macrophage infiltration (mean cells/mm2: 4M OVX, 1.18 [0.09] vs 12M OVX, 30.0 [0.74]; P < 0.001). E2 supplementation either partially or completely attenuated these changes in iNOS (mean ROD: 4M OVX+E2, 2.26 [0.08] vs 12M OVX+E2, 1.70 [0.09]; P < 0.05), eNOS (mean ROD: 4M OVX+E2, 2.03 [0.07] vs 12M OVX+E2, 1.77 [0.11]; P = NS) and CD68 (mean cells/mm2: 4M OVX+E2, 1.46 [0.07] vs 12M OVX+E2, 6.87 [1.6]; P < 0.01) associated with OVX in the aging kidney.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Aging', 'Animals', 'Blotting, Western', 'Diet, Sodium-Restricted', 'Disease Models, Animal', 'Down-Regulation', 'Estradiol', 'Female', 'Kidney', 'Kidney Failure, Chronic', 'Nitric Oxide Synthase Type II', 'Nitric Oxide Synthase Type III', 'Postmenopause', 'Rats', 'Rats, Inbred Dahl']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,555,976 | Do saliva indices track hypohydration during 48h of fluid restriction or combined fluid and energy restriction? | {
"contexts": [
"To investigate whether unstimulated whole saliva flow rate (UFR) and osmolality (Sosm) track changes in hydration status during 48h of restricted fluid intake (RF) or combined fluid and energy restriction (RF+RE). Following the 48h periods, UFR and Sosm were assessed after acute exercise dehydration and rehydration.",
"Thirteen healthy males completed three trials in a randomised order: control (CON) where participants received their estimated energy (12,154+/-230kJ/d: mean+/-S.E.M) and fluid (3912+/-140ml/d) requirements, RF trial where participants received their energy requirements and 193+/-19ml/d water to drink (total fluid 960+/-15ml/d) and RF+RE where participants received 1214+/-25kJ/d and 962+/-16ml/d. After 48h, participants completed 30min of maximal exercise followed by rehydration (0-2h) and refeeding (2-6h).",
"At 48h body mass loss exceeded 3% on RF and RF+RE. UFR decreased during 48h on RF (510+/-122 to 169+/-37microl/min) and RF+RE (452+/-92 to 265+/-53microl/min) and was lower than CON at 48h (441+/-90microl/min: P<0.05). Sosm increased during 48h on RF (54+/-3 to 73+/-5mOsmol/kg) and RF+RE (52+/-3 to 68+/-5mOsmol/kg) and was greater than CON at 48h (52+/-2mOsmol/kg: P<0.05). Unlike UFR, Sosm identified the additional hypohydration associated with exercise (P<0.05) and returned to within 0h values with rehydration."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Biomarkers",
"Dehydration",
"Energy Intake",
"Exercise",
"Fluid Therapy",
"Humans",
"Male",
"Motor Activity",
"Osmolar Concentration",
"Saliva",
"Salivation",
"Water Deprivation",
"Weight Loss",
"Young Adult"
]
} | Sosm, and to a lesser extent UFR, track hydration status during a 48h period of RF or RF+RE and after subsequent exercise and rehydration. | yes | [
{
"from": "human",
"value": "Question: Do saliva indices track hypohydration during 48h of fluid restriction or combined fluid and energy restriction?\nContext: {'contexts': ['To investigate whether unstimulated whole saliva flow rate (UFR) and osmolality (Sosm) track changes in hydration status during 48h of restricted fluid intake (RF) or combined fluid and energy restriction (RF+RE). Following the 48h periods, UFR and Sosm were assessed after acute exercise dehydration and rehydration.', 'Thirteen healthy males completed three trials in a randomised order: control (CON) where participants received their estimated energy (12,154+/-230kJ/d: mean+/-S.E.M) and fluid (3912+/-140ml/d) requirements, RF trial where participants received their energy requirements and 193+/-19ml/d water to drink (total fluid 960+/-15ml/d) and RF+RE where participants received 1214+/-25kJ/d and 962+/-16ml/d. After 48h, participants completed 30min of maximal exercise followed by rehydration (0-2h) and refeeding (2-6h).', 'At 48h body mass loss exceeded 3% on RF and RF+RE. UFR decreased during 48h on RF (510+/-122 to 169+/-37microl/min) and RF+RE (452+/-92 to 265+/-53microl/min) and was lower than CON at 48h (441+/-90microl/min: P<0.05). Sosm increased during 48h on RF (54+/-3 to 73+/-5mOsmol/kg) and RF+RE (52+/-3 to 68+/-5mOsmol/kg) and was greater than CON at 48h (52+/-2mOsmol/kg: P<0.05). Unlike UFR, Sosm identified the additional hypohydration associated with exercise (P<0.05) and returned to within 0h values with rehydration.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Biomarkers', 'Dehydration', 'Energy Intake', 'Exercise', 'Fluid Therapy', 'Humans', 'Male', 'Motor Activity', 'Osmolar Concentration', 'Saliva', 'Salivation', 'Water Deprivation', 'Weight Loss', 'Young Adult']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,560,454 | Does [ Hepatitis B surface antigen terminate codon bias selection ]? | {
"contexts": [
"To investigate the existence condition of hepatitis B surface antigen(HBsAg) termination codon bias.",
"A total of 174 reference sequences of all kinds of Hepatitis B virus(HBV) genotypes were chosen from GenBank, and compared by BioEdit. Then secondary structure of RNA was constructed and analyzed together.",
"(1) There were two types of HBsAg termination codon: TAA and TGA in 174 reference sequences. TAA was in 124 cases (71.26%); and TGA in 50 cases (28.74%). (2) There was codon bias selection in HBsAg termination codon, and it could affect the secondary structure of RNA and amino acid sequence encoding protein."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Base Sequence",
"Codon, Terminator",
"Genotype",
"Hepatitis B Surface Antigens",
"Hepatitis B virus",
"Humans",
"Molecular Sequence Data",
"Nucleic Acid Conformation",
"RNA",
"Selection Bias"
]
} | HBsAg termination codon bias exists and may be related to RNA structure and the conservation of protein function in the evolutionary progress. | yes | [
{
"from": "human",
"value": "Question: Does [ Hepatitis B surface antigen terminate codon bias selection ]?\nContext: {'contexts': ['To investigate the existence condition of hepatitis B surface antigen(HBsAg) termination codon bias.', 'A total of 174 reference sequences of all kinds of Hepatitis B virus(HBV) genotypes were chosen from GenBank, and compared by BioEdit. Then secondary structure of RNA was constructed and analyzed together.', '(1) There were two types of HBsAg termination codon: TAA and TGA in 174 reference sequences. TAA was in 124 cases (71.26%); and TGA in 50 cases (28.74%). (2) There was codon bias selection in HBsAg termination codon, and it could affect the secondary structure of RNA and amino acid sequence encoding protein.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Base Sequence', 'Codon, Terminator', 'Genotype', 'Hepatitis B Surface Antigens', 'Hepatitis B virus', 'Humans', 'Molecular Sequence Data', 'Nucleic Acid Conformation', 'RNA', 'Selection Bias']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,564,254 | Do autogenous osteochondral grafting for treatment of stifle osteochondrosis in dogs? | {
"contexts": [
"To develop and assess clinical outcomes for osteochondral autografting for treatment of stifle osteochondrosis (OC) in dogs.",
"Retrospective case series.",
"Dogs with stifle OC (n=10).",
"Osteochondral autografting was developed and optimized in canine cadavers and purpose-bred research dogs using the Osteochondral Autograft Transfer System (OATS). Dogs with stifle OC (n=10 dogs, 12 stifles) were then treated using the OATS system. Outcomes were assessed by radiography (n=12), magnetic resonance imaging (1), second-look arthroscopy (9), lameness scoring (12), and telephone survey of owners (10 clients, 12 stifles) 6-15 months after surgery.",
"Complications were documented in 4 of the 12 stifles treated and included peri-incisional seromas (3) and marked stifle effusion (1). Subjective assessment of follow-up radiographs revealed evidence of integration of the grafts with maintenance of subchondral bone surface architecture. Subjective assessment of follow-up MRI in 1 stifle revealed evidence for incorporation of grafts with restoration of articular surface contour. Second-look arthroscopy 6-30 weeks after surgery revealed maintenance of articular cartilage at the graft site. Dogs were significantly (P<.001) less lame at follow-up compared with preoperative scores. Based on follow-up owner surveys, only 2 dogs had no pain or lameness; the other dogs were judged to have mild pain and/or lameness. All owners noticed improvement in the dogs' quality of life after surgery."
],
"labels": [
"OBJECTIVE",
"METHODS",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Bone Transplantation",
"Dog Diseases",
"Dogs",
"Female",
"Follow-Up Studies",
"Lameness, Animal",
"Magnetic Resonance Imaging",
"Male",
"Osteochondritis",
"Postoperative Complications",
"Quality of Life",
"Retrospective Studies",
"Stifle",
"Treatment Outcome"
]
} | Osteochondral autografting deserves consideration and further evaluation as a primary treatment option for stifle OC in dogs. | yes | [
{
"from": "human",
"value": "Question: Do autogenous osteochondral grafting for treatment of stifle osteochondrosis in dogs?\nContext: {'contexts': ['To develop and assess clinical outcomes for osteochondral autografting for treatment of stifle osteochondrosis (OC) in dogs.', 'Retrospective case series.', 'Dogs with stifle OC (n=10).', 'Osteochondral autografting was developed and optimized in canine cadavers and purpose-bred research dogs using the Osteochondral Autograft Transfer System (OATS). Dogs with stifle OC (n=10 dogs, 12 stifles) were then treated using the OATS system. Outcomes were assessed by radiography (n=12), magnetic resonance imaging (1), second-look arthroscopy (9), lameness scoring (12), and telephone survey of owners (10 clients, 12 stifles) 6-15 months after surgery.', \"Complications were documented in 4 of the 12 stifles treated and included peri-incisional seromas (3) and marked stifle effusion (1). Subjective assessment of follow-up radiographs revealed evidence of integration of the grafts with maintenance of subchondral bone surface architecture. Subjective assessment of follow-up MRI in 1 stifle revealed evidence for incorporation of grafts with restoration of articular surface contour. Second-look arthroscopy 6-30 weeks after surgery revealed maintenance of articular cartilage at the graft site. Dogs were significantly (P<.001) less lame at follow-up compared with preoperative scores. Based on follow-up owner surveys, only 2 dogs had no pain or lameness; the other dogs were judged to have mild pain and/or lameness. All owners noticed improvement in the dogs' quality of life after surgery.\"], 'labels': ['OBJECTIVE', 'METHODS', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Bone Transplantation', 'Dog Diseases', 'Dogs', 'Female', 'Follow-Up Studies', 'Lameness, Animal', 'Magnetic Resonance Imaging', 'Male', 'Osteochondritis', 'Postoperative Complications', 'Quality of Life', 'Retrospective Studies', 'Stifle', 'Treatment Outcome']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,560,559 | Does directed evolution generate a novel oncolytic virus for the treatment of colon cancer? | {
"contexts": [
"Viral-mediated oncolysis is a novel cancer therapeutic approach with the potential to be more effective and less toxic than current therapies due to the agents selective growth and amplification in tumor cells. To date, these agents have been highly safe in patients but have generally fallen short of their expected therapeutic value as monotherapies. Consequently, new approaches to generating highly potent oncolytic viruses are needed. To address this need, we developed a new method that we term \"Directed Evolution\" for creating highly potent oncolytic viruses.",
"Taking the \"Directed Evolution\" approach, viral diversity was increased by pooling an array of serotypes, then passaging the pools under conditions that invite recombination between serotypes. These highly diverse viral pools were then placed under stringent directed selection to generate and identify highly potent agents. ColoAd1, a complex Ad3/Ad11p chimeric virus, was the initial oncolytic virus derived by this novel methodology. ColoAd1, the first described non-Ad5-based oncolytic Ad, is 2-3 logs more potent and selective than the parent serotypes or the most clinically advanced oncolytic Ad, ONYX-015, in vitro. ColoAd1's efficacy was further tested in vivo in a colon cancer liver metastasis xenograft model following intravenous injection and its ex vivo selectivity was demonstrated on surgically-derived human colorectal tumor tissues. Lastly, we demonstrated the ability to arm ColoAd1 with an exogenous gene establishing the potential to impact the treatment of cancer on multiple levels from a single agent."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Adenoviridae",
"Animals",
"Cell Line, Tumor",
"Colonic Neoplasms",
"Directed Molecular Evolution",
"Humans",
"Liver Neoplasms",
"Mice",
"Neoplasm Transplantation",
"Oncolytic Virotherapy",
"Oncolytic Viruses"
]
} | Using the "Directed Evolution" methodology, we have generated ColoAd1, a novel chimeric oncolytic virus. In vitro, this virus demonstrated a >2 log increase in both potency and selectivity when compared to ONYX-015 on colon cancer cells. These results were further supported by in vivo and ex vivo studies. Furthermore, these results have validated this methodology as a new general approach for deriving clinically-relevant, highly potent anti-cancer virotherapies. | yes | [
{
"from": "human",
"value": "Question: Does directed evolution generate a novel oncolytic virus for the treatment of colon cancer?\nContext: {'contexts': ['Viral-mediated oncolysis is a novel cancer therapeutic approach with the potential to be more effective and less toxic than current therapies due to the agents selective growth and amplification in tumor cells. To date, these agents have been highly safe in patients but have generally fallen short of their expected therapeutic value as monotherapies. Consequently, new approaches to generating highly potent oncolytic viruses are needed. To address this need, we developed a new method that we term \"Directed Evolution\" for creating highly potent oncolytic viruses.', 'Taking the \"Directed Evolution\" approach, viral diversity was increased by pooling an array of serotypes, then passaging the pools under conditions that invite recombination between serotypes. These highly diverse viral pools were then placed under stringent directed selection to generate and identify highly potent agents. ColoAd1, a complex Ad3/Ad11p chimeric virus, was the initial oncolytic virus derived by this novel methodology. ColoAd1, the first described non-Ad5-based oncolytic Ad, is 2-3 logs more potent and selective than the parent serotypes or the most clinically advanced oncolytic Ad, ONYX-015, in vitro. ColoAd1\\'s efficacy was further tested in vivo in a colon cancer liver metastasis xenograft model following intravenous injection and its ex vivo selectivity was demonstrated on surgically-derived human colorectal tumor tissues. Lastly, we demonstrated the ability to arm ColoAd1 with an exogenous gene establishing the potential to impact the treatment of cancer on multiple levels from a single agent.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Adenoviridae', 'Animals', 'Cell Line, Tumor', 'Colonic Neoplasms', 'Directed Molecular Evolution', 'Humans', 'Liver Neoplasms', 'Mice', 'Neoplasm Transplantation', 'Oncolytic Virotherapy', 'Oncolytic Viruses']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,551,562 | Do unilateral versus bilateral stage I neuromodulator lead placement for the treatment of refractory voiding dysfunction? | {
"contexts": [
"To determine if bilateral S3 lead placement during the stage I trial period improves the \"success\" rate for advancing to stage II (permanent) sacral neuromodulator placement.",
"A retrospective chart review of 124 (20 male and 104 female) patients undergoing stage I sacral neuromodulation (InterStim, Medtronic, Minneapolis, Minnesota) implantation for the treatment of refractory voiding dysfunction was performed. Patients were divided into two cohorts based on unilateral versus bilateral stage I lead placement in the S3 foramina. Both groups were then evaluated and compared with regards to overall \"success\", defined as progression from stage I to stage II placement.",
"Fifty-five (44%) patients underwent unilateral stage I lead placement and 69 (56%) received bilateral S3 leads. Successful stage I trials were reported in 32/55 (58%) and 53/69 (76%) of unilateral and bilateral cohorts, respectively (P = 0.03). Five wound infections were reported-2 (3.6%) following unilateral and 3 (4.3%) after bilateral stage I lead placement. No other complications were encountered."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Chronic Disease",
"Electric Stimulation Therapy",
"Electrodes, Implanted",
"Female",
"Humans",
"Lumbosacral Plexus",
"Male",
"Middle Aged",
"Pain Measurement",
"Pelvic Pain",
"Retrospective Studies",
"Treatment Outcome",
"Urinary Incontinence",
"Urinary Retention",
"Urodynamics"
]
} | Bilateral stage I neuromodulation trial provides a significantly higher rate of improvement in refractory voiding symptoms to allow for the progress to stage II implantation. | yes | [
{
"from": "human",
"value": "Question: Do unilateral versus bilateral stage I neuromodulator lead placement for the treatment of refractory voiding dysfunction?\nContext: {'contexts': ['To determine if bilateral S3 lead placement during the stage I trial period improves the \"success\" rate for advancing to stage II (permanent) sacral neuromodulator placement.', 'A retrospective chart review of 124 (20 male and 104 female) patients undergoing stage I sacral neuromodulation (InterStim, Medtronic, Minneapolis, Minnesota) implantation for the treatment of refractory voiding dysfunction was performed. Patients were divided into two cohorts based on unilateral versus bilateral stage I lead placement in the S3 foramina. Both groups were then evaluated and compared with regards to overall \"success\", defined as progression from stage I to stage II placement.', 'Fifty-five (44%) patients underwent unilateral stage I lead placement and 69 (56%) received bilateral S3 leads. Successful stage I trials were reported in 32/55 (58%) and 53/69 (76%) of unilateral and bilateral cohorts, respectively (P = 0.03). Five wound infections were reported-2 (3.6%) following unilateral and 3 (4.3%) after bilateral stage I lead placement. No other complications were encountered.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Chronic Disease', 'Electric Stimulation Therapy', 'Electrodes, Implanted', 'Female', 'Humans', 'Lumbosacral Plexus', 'Male', 'Middle Aged', 'Pain Measurement', 'Pelvic Pain', 'Retrospective Studies', 'Treatment Outcome', 'Urinary Incontinence', 'Urinary Retention', 'Urodynamics']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,552,031 | Do [ Guinea pig as often object to otoneurological experimental examinations ]? | {
"contexts": [
"The aim of this research was to describe nomograms of brainstem auditory evoked potentials, oscillating stimulation of the vestibular organs and ultrastructural research methodology of a spiral organ of guinea-pigs.",
"For the experimental purposes 60 guinea-pigs of both sexes, weight 250-300 grams, were used as research materials. After general anesthesia with Ketalar dosed 100 milligrams per kilogram and with Fentanyl dosed 0.1 milliliter per kilogram of the body mass, brainstem auditory evoked potentials were registered and the oscillating chair test (no prior anesthesia). Was placed on an assistant's knees, who was sitting on a chair. Then the guinea-pigs were anesthetized with 35 per cent solution of chloral hydrate intraperitoneally (dosed 1 milliliter per kilogram of the body mass). For electron microscopic research membranous helix was collected bilaterally by the method of micropreparation. Qualitative observation was conducted in the Philips' electron microscope (EM 300).",
"On the basis of the obtained results it was concluded that the time of transmission between elements P1-P2 is constant and figures between 3.1 and 3.6 ms independently from a force of stimulation. Vestibular organs of a guinea-pig are more sensitive to high accelerations (17-12 degree/s2) than human vestibularl organs. However, their reaction is much weaker to lower accelerations (12-0 degree/s2)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Evoked Potentials, Auditory, Brain Stem",
"Female",
"Guinea Pigs",
"Humans",
"Male",
"Vestibular Function Tests",
"Vestibule, Labyrinth"
]
} | The processed nomograms of the brainstem auditory evoked potentials, oscillating stimulation of vestibular organs and methodology of ultrastructural research in guinea-pigs' spiral organs are expected to facilitate using them in experimental research. | yes | [
{
"from": "human",
"value": "Question: Do [ Guinea pig as often object to otoneurological experimental examinations ]?\nContext: {'contexts': ['The aim of this research was to describe nomograms of brainstem auditory evoked potentials, oscillating stimulation of the vestibular organs and ultrastructural research methodology of a spiral organ of guinea-pigs.', \"For the experimental purposes 60 guinea-pigs of both sexes, weight 250-300 grams, were used as research materials. After general anesthesia with Ketalar dosed 100 milligrams per kilogram and with Fentanyl dosed 0.1 milliliter per kilogram of the body mass, brainstem auditory evoked potentials were registered and the oscillating chair test (no prior anesthesia). Was placed on an assistant's knees, who was sitting on a chair. Then the guinea-pigs were anesthetized with 35 per cent solution of chloral hydrate intraperitoneally (dosed 1 milliliter per kilogram of the body mass). For electron microscopic research membranous helix was collected bilaterally by the method of micropreparation. Qualitative observation was conducted in the Philips' electron microscope (EM 300).\", 'On the basis of the obtained results it was concluded that the time of transmission between elements P1-P2 is constant and figures between 3.1 and 3.6 ms independently from a force of stimulation. Vestibular organs of a guinea-pig are more sensitive to high accelerations (17-12 degree/s2) than human vestibularl organs. However, their reaction is much weaker to lower accelerations (12-0 degree/s2).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Evoked Potentials, Auditory, Brain Stem', 'Female', 'Guinea Pigs', 'Humans', 'Male', 'Vestibular Function Tests', 'Vestibule, Labyrinth']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,556,938 | Do the efficacy of retrobulbar block anesthesia only in pars plana vitrectomy and transconjunctival sutureless vitrectomy? | {
"contexts": [
"To evaluate the adequacy of retrobulbar block anesthesia only in vitreoretinal surgery.",
"The study involved 90 patients, 25 who underwent 25-gauge transconjunctival sutureless vitrectomy and 65 who underwent 20-gauge standard pars plana vitrectomy. Twenty-five of the 90 patients also underwent combined phacoemulsification and posterior intraocular lens implantation. The efficacy of retrobulbar block anesthesia only was assessed by monitoring vital signs during surgery, reviewing patient responses to a questionnaire regarding their experience during surgery, and analyzing surgical outcomes.",
"Four patients complained of moderate pain during surgery, but no patient complained of severe pain. Infiltrative anesthesia was additionally required in 14 patients. No patient experienced intraoperative complications due to head movement. Increased systolic blood pressure greater than 15 mm Hg occurred in 11 patients and increased respiratory rate by 3 breaths per minute or greater occurred in 7 patients. Anatomical and functional success rates were 95% and 80%, respectively. Complications included manageable retrobulbar bleeding (1 patient) and postoperative neovascular glaucoma (2 patients)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Aged, 80 and over",
"Anesthesia, Local",
"Anesthetics, Combined",
"Anesthetics, Local",
"Bupivacaine",
"Conjunctiva",
"Diazepam",
"Female",
"Humans",
"Lens Implantation, Intraocular",
"Lidocaine",
"Male",
"Microsurgery",
"Middle Aged",
"Nerve Block",
"Orbit",
"Pain Measurement",
"Pain, Postoperative",
"Phacoemulsification",
"Retinal Diseases",
"Suture Techniques",
"Vitrectomy",
"Vitreous Body"
]
} | Vitreoretinal surgery, particularly 25-gauge transconjunctival sutureless vitrectomy, can be safely and efficiently performed under retrobulbar block anesthesia only. Retrobulbar block anesthesia only could become a more acceptable anesthesia for vitreoretinal surgery for selected patients. | yes | [
{
"from": "human",
"value": "Question: Do the efficacy of retrobulbar block anesthesia only in pars plana vitrectomy and transconjunctival sutureless vitrectomy?\nContext: {'contexts': ['To evaluate the adequacy of retrobulbar block anesthesia only in vitreoretinal surgery.', 'The study involved 90 patients, 25 who underwent 25-gauge transconjunctival sutureless vitrectomy and 65 who underwent 20-gauge standard pars plana vitrectomy. Twenty-five of the 90 patients also underwent combined phacoemulsification and posterior intraocular lens implantation. The efficacy of retrobulbar block anesthesia only was assessed by monitoring vital signs during surgery, reviewing patient responses to a questionnaire regarding their experience during surgery, and analyzing surgical outcomes.', 'Four patients complained of moderate pain during surgery, but no patient complained of severe pain. Infiltrative anesthesia was additionally required in 14 patients. No patient experienced intraoperative complications due to head movement. Increased systolic blood pressure greater than 15 mm Hg occurred in 11 patients and increased respiratory rate by 3 breaths per minute or greater occurred in 7 patients. Anatomical and functional success rates were 95% and 80%, respectively. Complications included manageable retrobulbar bleeding (1 patient) and postoperative neovascular glaucoma (2 patients).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Aged, 80 and over', 'Anesthesia, Local', 'Anesthetics, Combined', 'Anesthetics, Local', 'Bupivacaine', 'Conjunctiva', 'Diazepam', 'Female', 'Humans', 'Lens Implantation, Intraocular', 'Lidocaine', 'Male', 'Microsurgery', 'Middle Aged', 'Nerve Block', 'Orbit', 'Pain Measurement', 'Pain, Postoperative', 'Phacoemulsification', 'Retinal Diseases', 'Suture Techniques', 'Vitrectomy', 'Vitreous Body']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,552,133 | Does motion-frozen myocardial perfusion SPECT improve detection of coronary artery disease in obese patients? | {
"contexts": [
"In this study, we compared the diagnostic performance of the standard SPECT with motion-frozen (MF) myocardial perfusion SPECT (MPS) in obese patients.",
"A total of 90 consecutive obese patients (body mass index, 30.1-46.8, average, 34.3 +/- 3.6; age, 63 +/- 12 y; 30% women) underwent standard supine rest (201)Tl/stress (99m)Tc dual-isotope gated MPS and cardiac catheterization within 3 mo. MF images were obtained by nonlinear warping of cardiac phases to the end-diastolic position. Total perfusion deficit (TPD) was obtained for summed (S-TPD) and motion-frozen (MF-TPD) datasets with sex-specific standard and MF normal limits.",
"The area under the receiver-operating-characteristic (ROC) curve for detection of coronary artery disease (CAD) by MF-TPD was significantly larger than that for S-TPD (0.93 +/- 0.25 vs. 0.88 +/- 0.32, P < 0.05). MF-TPD had higher specificity (77% vs. 55%, P < 0.05) and accuracy (89% vs. 80%, P < 0.05) than did S-TPD."
],
"labels": [
"UNLABELLED",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Aged, 80 and over",
"Coronary Artery Disease",
"Coronary Circulation",
"Female",
"Heart",
"Humans",
"Image Interpretation, Computer-Assisted",
"Male",
"Middle Aged",
"Motion",
"Obesity",
"Tomography, Emission-Computed, Single-Photon"
]
} | MF processing of MPS improves CAD detection in obese patients. | yes | [
{
"from": "human",
"value": "Question: Does motion-frozen myocardial perfusion SPECT improve detection of coronary artery disease in obese patients?\nContext: {'contexts': ['In this study, we compared the diagnostic performance of the standard SPECT with motion-frozen (MF) myocardial perfusion SPECT (MPS) in obese patients.', 'A total of 90 consecutive obese patients (body mass index, 30.1-46.8, average, 34.3 +/- 3.6; age, 63 +/- 12 y; 30% women) underwent standard supine rest (201)Tl/stress (99m)Tc dual-isotope gated MPS and cardiac catheterization within 3 mo. MF images were obtained by nonlinear warping of cardiac phases to the end-diastolic position. Total perfusion deficit (TPD) was obtained for summed (S-TPD) and motion-frozen (MF-TPD) datasets with sex-specific standard and MF normal limits.', 'The area under the receiver-operating-characteristic (ROC) curve for detection of coronary artery disease (CAD) by MF-TPD was significantly larger than that for S-TPD (0.93 +/- 0.25 vs. 0.88 +/- 0.32, P < 0.05). MF-TPD had higher specificity (77% vs. 55%, P < 0.05) and accuracy (89% vs. 80%, P < 0.05) than did S-TPD.'], 'labels': ['UNLABELLED', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Aged, 80 and over', 'Coronary Artery Disease', 'Coronary Circulation', 'Female', 'Heart', 'Humans', 'Image Interpretation, Computer-Assisted', 'Male', 'Middle Aged', 'Motion', 'Obesity', 'Tomography, Emission-Computed, Single-Photon']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,545,987 | Does a schizophrenia-linked mutation in PIP5K2A fail to activate neuronal M channels? | {
"contexts": [
"Evidence for an association between phosphatidylinositol-4-phosphate 5-kinase II alpha (PIP5K2A) and schizophrenia was recently obtained and replicated in several samples. PIP5K2A controls the function of KCNQ channels via phosphatidylinositol-4,5-bisphosphate (PIP2) synthesis. Interestingly, recent data suggest that KCNQ channels suppress basal activity of dopaminergic neurons and dopaminergic firing. Activation of KCNQ accordingly attenuates the central stimulating effects of dopamine, cocaine, methylphenidate, and phenylcyclidine.",
"The aim of this study was to explore the functional relevance of PIP5K2A, which might influence schizophrenic behavior.",
"Here, we study the effects of the neuronal PIP5K2A on KCNQ2, KCNQ5, KCNQ2/KCNQ3, and KCNQ3/KCNQ5 in the Xenopus expression system.",
"We find that wild-type PIP5K2A but not the schizophrenia-associated mutant (N251S)-PIP5K2A activates heteromeric KCNQ2/KCNQ3 and KCNQ3/KCNQ5, the molecular correlate of neuronal M channels. Homomeric KCNQ2 and KCNQ5 channels were not activated by the kinase indicating that the presence of KCNQ3 in the channel complex is required for the kinase-mediated effects. Acute application of PI(4,5)P2 and a PIP2 scavenger indicates that the mutation N251S renders the kinase PIP5K2A inactive."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Alleles",
"Animals",
"DNA Mutational Analysis",
"Dopamine",
"Humans",
"KCNQ Potassium Channels",
"Neurons",
"Oocytes",
"Patch-Clamp Techniques",
"Phenotype",
"Phosphotransferases (Alcohol Group Acceptor)",
"Schizophrenia",
"Substrate Specificity",
"Xenopus laevis"
]
} | Our results suggest that the schizophrenia-linked mutation of the kinase results in reduced KCNQ channel function and thereby might explain the loss of dopaminergic control in schizophrenic patients. Moreover, the addictive potential of dopaminergic drugs often observed in schizophrenic patients might be explained by this mechanism. At least, the insufficiency of (N251S)-PIP5K2A to stimulate neuronal M channels may contribute to the clinical phenotype of schizophrenia. | yes | [
{
"from": "human",
"value": "Question: Does a schizophrenia-linked mutation in PIP5K2A fail to activate neuronal M channels?\nContext: {'contexts': ['Evidence for an association between phosphatidylinositol-4-phosphate 5-kinase II alpha (PIP5K2A) and schizophrenia was recently obtained and replicated in several samples. PIP5K2A controls the function of KCNQ channels via phosphatidylinositol-4,5-bisphosphate (PIP2) synthesis. Interestingly, recent data suggest that KCNQ channels suppress basal activity of dopaminergic neurons and dopaminergic firing. Activation of KCNQ accordingly attenuates the central stimulating effects of dopamine, cocaine, methylphenidate, and phenylcyclidine.', 'The aim of this study was to explore the functional relevance of PIP5K2A, which might influence schizophrenic behavior.', 'Here, we study the effects of the neuronal PIP5K2A on KCNQ2, KCNQ5, KCNQ2/KCNQ3, and KCNQ3/KCNQ5 in the Xenopus expression system.', 'We find that wild-type PIP5K2A but not the schizophrenia-associated mutant (N251S)-PIP5K2A activates heteromeric KCNQ2/KCNQ3 and KCNQ3/KCNQ5, the molecular correlate of neuronal M channels. Homomeric KCNQ2 and KCNQ5 channels were not activated by the kinase indicating that the presence of KCNQ3 in the channel complex is required for the kinase-mediated effects. Acute application of PI(4,5)P2 and a PIP2 scavenger indicates that the mutation N251S renders the kinase PIP5K2A inactive.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Alleles', 'Animals', 'DNA Mutational Analysis', 'Dopamine', 'Humans', 'KCNQ Potassium Channels', 'Neurons', 'Oocytes', 'Patch-Clamp Techniques', 'Phenotype', 'Phosphotransferases (Alcohol Group Acceptor)', 'Schizophrenia', 'Substrate Specificity', 'Xenopus laevis']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,568,131 | Does overexpression of a mutant form of TGFBI/BIGH3 induce retinal degeneration in transgenic mice? | {
"contexts": [
"Despite ubiquitous expression of the keratoepithelin (KE) protein encoded by the transforming growth factor beta induced/beta induced gene human clone 3 (TGFBI/BIGH3) gene, corneal dystrophies are restricted to the cornea, and no other tissues are affected. We investigated the role of TGFBI/BIGH3 in Groenouw corneal dystrophies by generating transgenic mice overexpressing TGFBI/BIGH3 containing the R555W mutation.",
"Transgenic animals expressing the Groenouw mutation of human TGFBI/BIGH3 were generated using lentiviral vectors. The line expressed TGFBI/BIGH3 containing the R555W mutation under the control of the phosphoglycerate kinase (PGK) promoter. Expression of the transgene was monitored by Southern and western blotting and by RT-PCR. Electroretinogram analysis was performed and four mice were subjected to complete necroscopy.",
"Transgene expression was observed in different organs although without specific expression in the cornea. The overall morphology of the transgenic animals was not severely affected by KE overexpression. However, we observed an age-dependent retinal degeneration both functionally and histologically. Female-specific follicular hyperplasia in the spleen and increased levels of lipofuscin in the adrenal gland were also seen in transgenic animals."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Blotting, Southern",
"Blotting, Western",
"Electroretinography",
"Extracellular Matrix Proteins",
"Female",
"Gene Expression Regulation",
"Humans",
"Hyperplasia",
"Lentivirus",
"Male",
"Mice",
"Mice, Transgenic",
"Mutant Proteins",
"Organ Size",
"Organ Specificity",
"Phosphoglycerate Kinase",
"Promoter Regions, Genetic",
"RNA, Messenger",
"Reproducibility of Results",
"Retinal Degeneration",
"Spleen",
"Transforming Growth Factor beta",
"Virus Integration"
]
} | Cellular degeneration in the retina of transgenic animals suggest that perturbation of the transforming growth factor beta (TGFbeta) family regulation may affect photoreceptor survival and may induce possible accelerated aging in several tissues. No corneal phenotype could be observed, probably due to the lack of transgene expression in this tissue. | yes | [
{
"from": "human",
"value": "Question: Does overexpression of a mutant form of TGFBI/BIGH3 induce retinal degeneration in transgenic mice?\nContext: {'contexts': ['Despite ubiquitous expression of the keratoepithelin (KE) protein encoded by the transforming growth factor beta induced/beta induced gene human clone 3 (TGFBI/BIGH3) gene, corneal dystrophies are restricted to the cornea, and no other tissues are affected. We investigated the role of TGFBI/BIGH3 in Groenouw corneal dystrophies by generating transgenic mice overexpressing TGFBI/BIGH3 containing the R555W mutation.', 'Transgenic animals expressing the Groenouw mutation of human TGFBI/BIGH3 were generated using lentiviral vectors. The line expressed TGFBI/BIGH3 containing the R555W mutation under the control of the phosphoglycerate kinase (PGK) promoter. Expression of the transgene was monitored by Southern and western blotting and by RT-PCR. Electroretinogram analysis was performed and four mice were subjected to complete necroscopy.', 'Transgene expression was observed in different organs although without specific expression in the cornea. The overall morphology of the transgenic animals was not severely affected by KE overexpression. However, we observed an age-dependent retinal degeneration both functionally and histologically. Female-specific follicular hyperplasia in the spleen and increased levels of lipofuscin in the adrenal gland were also seen in transgenic animals.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Blotting, Southern', 'Blotting, Western', 'Electroretinography', 'Extracellular Matrix Proteins', 'Female', 'Gene Expression Regulation', 'Humans', 'Hyperplasia', 'Lentivirus', 'Male', 'Mice', 'Mice, Transgenic', 'Mutant Proteins', 'Organ Size', 'Organ Specificity', 'Phosphoglycerate Kinase', 'Promoter Regions, Genetic', 'RNA, Messenger', 'Reproducibility of Results', 'Retinal Degeneration', 'Spleen', 'Transforming Growth Factor beta', 'Virus Integration']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,563,791 | Is intermittent Pringle manoeuvre associated with adverse long-term prognosis after resection for colorectal liver metastases? | {
"contexts": [
"Intermittent clamping of the porta hepatis, or the intermittent Pringle manoeuvre (IPM), is often used to control inflow during parenchymal liver transection. The aim of this study was to determine whether IPM is associated with an adverse long-term outcome after liver resection for colorectal liver metastasis (CRLM).",
"All patients undergoing resection for CRLM in 1993-2006, for whom data on IPM were recorded, were included in the study. A total of 563 patients was available for analysis.",
"IPM was performed in 289 (51.3 per cent) of the patients. The duration of IPM ranged from 2 to 104 (median 22) min. There were no differences in clinicopathological features or postoperative morbidity between patients who had an IPM and those who did not. The median survival of patients undergoing IPM was 55.7 months compared with 48.9 months in those not having an IPM (P = 0.406). There was no difference in median disease-free survival between the two groups (22.1 versus 19.9 months respectively; P = 0.199)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Blood Loss, Surgical",
"Colorectal Neoplasms",
"Constriction",
"Epidemiologic Methods",
"Female",
"Hepatectomy",
"Humans",
"Liver Neoplasms",
"Male",
"Prognosis",
"Treatment Outcome"
]
} | IPM is not associated with an adverse long-term prognosis in patients undergoing liver resection for CRLM. | no | [
{
"from": "human",
"value": "Question: Is intermittent Pringle manoeuvre associated with adverse long-term prognosis after resection for colorectal liver metastases?\nContext: {'contexts': ['Intermittent clamping of the porta hepatis, or the intermittent Pringle manoeuvre (IPM), is often used to control inflow during parenchymal liver transection. The aim of this study was to determine whether IPM is associated with an adverse long-term outcome after liver resection for colorectal liver metastasis (CRLM).', 'All patients undergoing resection for CRLM in 1993-2006, for whom data on IPM were recorded, were included in the study. A total of 563 patients was available for analysis.', 'IPM was performed in 289 (51.3 per cent) of the patients. The duration of IPM ranged from 2 to 104 (median 22) min. There were no differences in clinicopathological features or postoperative morbidity between patients who had an IPM and those who did not. The median survival of patients undergoing IPM was 55.7 months compared with 48.9 months in those not having an IPM (P = 0.406). There was no difference in median disease-free survival between the two groups (22.1 versus 19.9 months respectively; P = 0.199).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Aged', 'Blood Loss, Surgical', 'Colorectal Neoplasms', 'Constriction', 'Epidemiologic Methods', 'Female', 'Hepatectomy', 'Humans', 'Liver Neoplasms', 'Male', 'Prognosis', 'Treatment Outcome']}"
},
{
"from": "gpt",
"value": "Answer: no"
}
]
|
18,554,641 | Are posterior urethral valves often associated with cryptorchidism and inguinal hernias? | {
"contexts": [
"We evaluated the incidence of cryptorchidism and inguinal hernias in patients with posterior urethral valves, and compared characteristics in patients with and without cryptorchidism or inguinal hernia.",
"A total of 200 patients with posterior urethral valves treated between 1953 and 2003 were identified from a hospital database. Patient records were retrospectively reviewed. The state of testicular descent and the presence of inguinal hernias were recorded in 192 patients. Patient characteristics were analyzed.",
"Of 192 patients 31 (16%) had cryptorchidism, which was bilateral in 9 (29%). A total of 21 patients (11%) had inguinal hernias that were not associated with cryptorchid testes. The patients with cryptorchidism, and to some extent the patients with hernias, appeared to have a more severe form of posterior urethral valves than those without cryptorchidism. At the time of diagnosis the median serum creatinine concentration was 100 mumol/l (range 38 to 460) in boys with cryptorchidism and 87 (14 to 593) in boys without cryptorchidism (p = 0.131). At 6-month followup the median serum creatinine levels were 90 mumol/l (range 31 to 573) in patients with cryptorchidism and 45 (19 to 504) in patients without cryptorchidism (p = 0.006). Cryptorchidism was also more common in cases diagnosed neonatally compared to those diagnosed at a later age (14 of 52 patients, 27% vs 14 of 112, 12.5%, respectively, p = 0.027)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Age Factors",
"Case-Control Studies",
"Child",
"Child, Preschool",
"Cryptorchidism",
"Follow-Up Studies",
"Hernia, Inguinal",
"Humans",
"Incidence",
"Infant",
"Infant, Newborn",
"Male",
"Probability",
"Reference Values",
"Registries",
"Retrospective Studies",
"Statistics, Nonparametric",
"Treatment Outcome",
"Urethra",
"Urogenital Abnormalities"
]
} | The incidence of cryptorchidism and inguinal hernias requiring surgery is high in patients with posterior urethral valves. Patients with cryptorchidism appear to have a more severe form of posterior urethral valves than those with normal testes. | yes | [
{
"from": "human",
"value": "Question: Are posterior urethral valves often associated with cryptorchidism and inguinal hernias?\nContext: {'contexts': ['We evaluated the incidence of cryptorchidism and inguinal hernias in patients with posterior urethral valves, and compared characteristics in patients with and without cryptorchidism or inguinal hernia.', 'A total of 200 patients with posterior urethral valves treated between 1953 and 2003 were identified from a hospital database. Patient records were retrospectively reviewed. The state of testicular descent and the presence of inguinal hernias were recorded in 192 patients. Patient characteristics were analyzed.', 'Of 192 patients 31 (16%) had cryptorchidism, which was bilateral in 9 (29%). A total of 21 patients (11%) had inguinal hernias that were not associated with cryptorchid testes. The patients with cryptorchidism, and to some extent the patients with hernias, appeared to have a more severe form of posterior urethral valves than those without cryptorchidism. At the time of diagnosis the median serum creatinine concentration was 100 mumol/l (range 38 to 460) in boys with cryptorchidism and 87 (14 to 593) in boys without cryptorchidism (p = 0.131). At 6-month followup the median serum creatinine levels were 90 mumol/l (range 31 to 573) in patients with cryptorchidism and 45 (19 to 504) in patients without cryptorchidism (p = 0.006). Cryptorchidism was also more common in cases diagnosed neonatally compared to those diagnosed at a later age (14 of 52 patients, 27% vs 14 of 112, 12.5%, respectively, p = 0.027).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Age Factors', 'Case-Control Studies', 'Child', 'Child, Preschool', 'Cryptorchidism', 'Follow-Up Studies', 'Hernia, Inguinal', 'Humans', 'Incidence', 'Infant', 'Infant, Newborn', 'Male', 'Probability', 'Reference Values', 'Registries', 'Retrospective Studies', 'Statistics, Nonparametric', 'Treatment Outcome', 'Urethra', 'Urogenital Abnormalities']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,545,685 | Is tamoxifen effective in the treatment of Leishmania amazonensis infections in mice? | {
"contexts": [
"Chemotherapy is still a critical issue in the management of leishmaniasis. Until recently, pentavalent antimonials, amphotericin B or pentamidine compounded the classical arsenal of treatment. All these drugs are toxic and have to be administered by the parenteral route. Tamoxifen has been used as an antiestrogen in the treatment and prevention of breast cancer for many years. Its safety and pharmacological profiles are well established in humans. We have shown that tamoxifen is active as an antileishmanial compound in vitro, and in this paper we analyzed the efficacy of tamoxifen for the treatment of mice infected with Leishmania amazonensis, an etiological agent of localized cutaneous leishmaniasis and the main cause of diffuse cutaneous leishmaniasis in South America.",
"BALB/c mice were infected with L. amazonensis promastigotes. Five weeks post-infection, treatment with 15 daily intraperitoneal injections of 20 mg/kg tamoxifen was administered. Lesion and ulcer sizes were recorded and parasite burden quantified by limiting dilution. A significant decrease in lesion size and ulcer development was noted in mice treated with tamoxifen as compared to control untreated animals. Parasite burden in the inoculation site at the end of treatment was reduced from 10(8.5+/-0.7) in control untreated animals to 10(5.0+/-0.0) in tamoxifen-treated mice. Parasite load was also reduced in the draining lymph nodes. The reduction in parasite number was sustained: 6 weeks after the end of treatment, 10(15.5+/-0.5) parasites were quantified from untreated animals, as opposed to 10(5.1+/-0.1) parasites detected in treated mice."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Animals",
"Female",
"Leishmania",
"Leishmaniasis",
"Mice",
"Mice, Inbred BALB C",
"Tamoxifen",
"Trypanocidal Agents"
]
} | Treatment of BALB/c mice infected with L. amazonensis for 15 days with tamoxifen resulted in significant decrease in lesion size and parasite burden. BALB/c mice infected with L. amazonensis represents a model of extreme susceptibility, and the striking and sustained reduction in the number of parasites in treated animals supports the proposal of further testing of this drug in other models of leishmaniasis. | yes | [
{
"from": "human",
"value": "Question: Is tamoxifen effective in the treatment of Leishmania amazonensis infections in mice?\nContext: {'contexts': ['Chemotherapy is still a critical issue in the management of leishmaniasis. Until recently, pentavalent antimonials, amphotericin B or pentamidine compounded the classical arsenal of treatment. All these drugs are toxic and have to be administered by the parenteral route. Tamoxifen has been used as an antiestrogen in the treatment and prevention of breast cancer for many years. Its safety and pharmacological profiles are well established in humans. We have shown that tamoxifen is active as an antileishmanial compound in vitro, and in this paper we analyzed the efficacy of tamoxifen for the treatment of mice infected with Leishmania amazonensis, an etiological agent of localized cutaneous leishmaniasis and the main cause of diffuse cutaneous leishmaniasis in South America.', 'BALB/c mice were infected with L. amazonensis promastigotes. Five weeks post-infection, treatment with 15 daily intraperitoneal injections of 20 mg/kg tamoxifen was administered. Lesion and ulcer sizes were recorded and parasite burden quantified by limiting dilution. A significant decrease in lesion size and ulcer development was noted in mice treated with tamoxifen as compared to control untreated animals. Parasite burden in the inoculation site at the end of treatment was reduced from 10(8.5+/-0.7) in control untreated animals to 10(5.0+/-0.0) in tamoxifen-treated mice. Parasite load was also reduced in the draining lymph nodes. The reduction in parasite number was sustained: 6 weeks after the end of treatment, 10(15.5+/-0.5) parasites were quantified from untreated animals, as opposed to 10(5.1+/-0.1) parasites detected in treated mice.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Animals', 'Female', 'Leishmania', 'Leishmaniasis', 'Mice', 'Mice, Inbred BALB C', 'Tamoxifen', 'Trypanocidal Agents']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,543,025 | Is thrombosis confined to the portal vein a contraindication for living donor liver transplantation? | {
"contexts": [
"There is a lack of agreement regarding preexisting portal vein thrombosis (PVT) in patients undergoing living donor liver transplantation (LDLT). We report the results of a single-center study to determine the impact of PVT on outcomes of adult LDLT recipients.",
"Of 133 cases of adult LDLT performed between January 2000 and December 2004, a thrombectomy was performed on 22 patients (16.5%) with PVT during the transplant procedure. One hundred eleven patients without PVT (group 1) were compared with those with a thrombosis confined to the portal vein (group 2; n = 15) and patients with the thrombosis beyond the portal vein (group 3; n = 7).",
"The sensitivities of Doppler ultrasound and CT in detecting PVT were 50 and 63.6%. A prior history of variceal bleeding (OR = 10.6, p = 0.002) and surgical shunt surgery (OR = 28.1, p = 0.044) were found to be an independent risk factors for PVT. The rate of postoperative PVT was significantly higher in patients with PVT than in those without (18.2 vs. 2.7%; p = 0.014). In particular, the rethrombosis rate in group 3 was 28.6%. The actuarial 3-year patient survival rate in PVT patients (73.6%) was similar to that of the non-PVT patients (85.3%; p = 0.351). However, the actuarial 3-year patient survival rate in group 3 was 38.1%, which was significantly lower than that in groups 1 and 2 (p = 0.006)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Contraindications",
"Female",
"Graft Survival",
"Humans",
"Liver Transplantation",
"Living Donors",
"Logistic Models",
"Male",
"Middle Aged",
"Portal Vein",
"Prospective Studies",
"Risk Factors",
"Statistics, Nonparametric",
"Survival Rate",
"Thrombectomy",
"Tomography, X-Ray Computed",
"Treatment Outcome",
"Ultrasonography, Doppler",
"Venous Thrombosis"
]
} | A thrombosis confined to the portal vein per se should not be considered a contraindication for LDLT. | no | [
{
"from": "human",
"value": "Question: Is thrombosis confined to the portal vein a contraindication for living donor liver transplantation?\nContext: {'contexts': ['There is a lack of agreement regarding preexisting portal vein thrombosis (PVT) in patients undergoing living donor liver transplantation (LDLT). We report the results of a single-center study to determine the impact of PVT on outcomes of adult LDLT recipients.', 'Of 133 cases of adult LDLT performed between January 2000 and December 2004, a thrombectomy was performed on 22 patients (16.5%) with PVT during the transplant procedure. One hundred eleven patients without PVT (group 1) were compared with those with a thrombosis confined to the portal vein (group 2; n = 15) and patients with the thrombosis beyond the portal vein (group 3; n = 7).', 'The sensitivities of Doppler ultrasound and CT in detecting PVT were 50 and 63.6%. A prior history of variceal bleeding (OR = 10.6, p = 0.002) and surgical shunt surgery (OR = 28.1, p = 0.044) were found to be an independent risk factors for PVT. The rate of postoperative PVT was significantly higher in patients with PVT than in those without (18.2 vs. 2.7%; p = 0.014). In particular, the rethrombosis rate in group 3 was 28.6%. The actuarial 3-year patient survival rate in PVT patients (73.6%) was similar to that of the non-PVT patients (85.3%; p = 0.351). However, the actuarial 3-year patient survival rate in group 3 was 38.1%, which was significantly lower than that in groups 1 and 2 (p = 0.006).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Contraindications', 'Female', 'Graft Survival', 'Humans', 'Liver Transplantation', 'Living Donors', 'Logistic Models', 'Male', 'Middle Aged', 'Portal Vein', 'Prospective Studies', 'Risk Factors', 'Statistics, Nonparametric', 'Survival Rate', 'Thrombectomy', 'Tomography, X-Ray Computed', 'Treatment Outcome', 'Ultrasonography, Doppler', 'Venous Thrombosis']}"
},
{
"from": "gpt",
"value": "Answer: no"
}
]
|
18,557,830 | Do children with heavy prenatal alcohol exposure demonstrate deficits on multiple measures of concept formation? | {
"contexts": [
"Children with heavy prenatal alcohol exposure have documented impairments in executive functioning (EF). One component of EF, concept formation, has not been well studied in this group.",
"Children (8 to 18 years) with histories of heavy prenatal alcohol exposure, with and without fetal alcohol syndrome (FAS), were compared to typically developing controls on 2 measures of concept formation and conceptual set shifting: the Wisconsin Card Sorting Test and the Card Sorting Test from the Delis-Kaplan Executive Functioning System. In addition to between-group comparisons, performance relative to overall intellectual functioning was examined.",
"Children with histories of heavy prenatal alcohol exposure showed impairment on both tests of concept formation compared to non-exposed controls. These deficits included difficulty generating and verbalizing concepts, increased error rates and perseverative responses, and poorer response to feedback. However, in comparison to controls, alcohol-exposed children performed better on measures of concept formation than predicted by their overall IQ scores. Exploratory analyses suggest that this may be due to differences in how the measures relate at different IQ levels and may not be specific to prenatal alcohol exposure."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Activities of Daily Living",
"Adolescent",
"Case-Control Studies",
"Child",
"Concept Formation",
"Data Interpretation, Statistical",
"Female",
"Fetal Alcohol Spectrum Disorders",
"Humans",
"Intelligence Tests",
"Male",
"Neuropsychological Tests",
"Pregnancy",
"Prenatal Exposure Delayed Effects",
"Psychological Tests"
]
} | Deficits in concept formation and conceptual set shifting were observed in alcohol-exposed children with or without the diagnosis of FAS and in the absence of mental retardation. These deficits likely impact problem solving skills and adaptive functioning and have implications for therapeutic interventions in this population. | yes | [
{
"from": "human",
"value": "Question: Do children with heavy prenatal alcohol exposure demonstrate deficits on multiple measures of concept formation?\nContext: {'contexts': ['Children with heavy prenatal alcohol exposure have documented impairments in executive functioning (EF). One component of EF, concept formation, has not been well studied in this group.', 'Children (8 to 18 years) with histories of heavy prenatal alcohol exposure, with and without fetal alcohol syndrome (FAS), were compared to typically developing controls on 2 measures of concept formation and conceptual set shifting: the Wisconsin Card Sorting Test and the Card Sorting Test from the Delis-Kaplan Executive Functioning System. In addition to between-group comparisons, performance relative to overall intellectual functioning was examined.', 'Children with histories of heavy prenatal alcohol exposure showed impairment on both tests of concept formation compared to non-exposed controls. These deficits included difficulty generating and verbalizing concepts, increased error rates and perseverative responses, and poorer response to feedback. However, in comparison to controls, alcohol-exposed children performed better on measures of concept formation than predicted by their overall IQ scores. Exploratory analyses suggest that this may be due to differences in how the measures relate at different IQ levels and may not be specific to prenatal alcohol exposure.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Activities of Daily Living', 'Adolescent', 'Case-Control Studies', 'Child', 'Concept Formation', 'Data Interpretation, Statistical', 'Female', 'Fetal Alcohol Spectrum Disorders', 'Humans', 'Intelligence Tests', 'Male', 'Neuropsychological Tests', 'Pregnancy', 'Prenatal Exposure Delayed Effects', 'Psychological Tests']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,560,376 | Are escherichia coli colonizing the neurogenic bladder similar to widespread clones causing disease in patients with normal bladder function? | {
"contexts": [
"Clonal typing of neurogenic clones.",
"To determine whether neurogenic clones carried over weeks in the urine of asymptomatic children with neurogenic bladder were similar to known uropathogenic clones associated with disease.",
"Michigan State University; VA Medical Center, Minneapolis, MN, USA.",
"Escherichia coli isolates from the urine of 15 children previously followed were typed by multilocus sequence typing and compared to 2 human pyelonephritis genome strains, 29 pediatric or adult symptomatic urinary tract infection strains, 15 pediatric asymptomatic bacteriuria strains, 6 animal urinary tract infection strains and a neonatal meningitis-septicemia prototype K1 strain. Phylotypes and virulence genotypes were determined using PCR.",
"Twenty-nine E. coli isolates were classified into 15 clones. Six of 15 clones were the same sequence type or a close relative to a clone that caused disease in a human or animal. These clones were considered uropathogens. The remaining nine clones were not closely related to a clone that caused disease and were considered commensal clones. Uropathogens were predominantly group B2, exhibited more virulence genes and were carried for more weeks in the neurogenic bladder compared to commensal clones. Nine of 15 children carried one or more uropathogenic clones; 4 children carried one or more commensal clones and 2 children carried both uropathogenic and commensal clones."
],
"labels": [
"METHODS",
"OBJECTIVE",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Bacterial Adhesion",
"Bacteriuria",
"Base Sequence",
"Child",
"Clone Cells",
"Colony Count, Microbial",
"Cystitis",
"Escherichia coli",
"Escherichia coli Infections",
"Female",
"Genotype",
"Humans",
"Male",
"Phylogeny",
"Urinary Bladder, Neurogenic",
"Urinary Tract Infections",
"Virulence Factors"
]
} | Children with neurogenic bladder most commonly carried commensal clones. Uropathogenic clones were associated with prolonged carriage, however, carriage was not associated with symptomatic disease or deterioration of the upper urinary tract. | yes | [
{
"from": "human",
"value": "Question: Are escherichia coli colonizing the neurogenic bladder similar to widespread clones causing disease in patients with normal bladder function?\nContext: {'contexts': ['Clonal typing of neurogenic clones.', 'To determine whether neurogenic clones carried over weeks in the urine of asymptomatic children with neurogenic bladder were similar to known uropathogenic clones associated with disease.', 'Michigan State University; VA Medical Center, Minneapolis, MN, USA.', 'Escherichia coli isolates from the urine of 15 children previously followed were typed by multilocus sequence typing and compared to 2 human pyelonephritis genome strains, 29 pediatric or adult symptomatic urinary tract infection strains, 15 pediatric asymptomatic bacteriuria strains, 6 animal urinary tract infection strains and a neonatal meningitis-septicemia prototype K1 strain. Phylotypes and virulence genotypes were determined using PCR.', 'Twenty-nine E. coli isolates were classified into 15 clones. Six of 15 clones were the same sequence type or a close relative to a clone that caused disease in a human or animal. These clones were considered uropathogens. The remaining nine clones were not closely related to a clone that caused disease and were considered commensal clones. Uropathogens were predominantly group B2, exhibited more virulence genes and were carried for more weeks in the neurogenic bladder compared to commensal clones. Nine of 15 children carried one or more uropathogenic clones; 4 children carried one or more commensal clones and 2 children carried both uropathogenic and commensal clones.'], 'labels': ['METHODS', 'OBJECTIVE', 'METHODS', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Bacterial Adhesion', 'Bacteriuria', 'Base Sequence', 'Child', 'Clone Cells', 'Colony Count, Microbial', 'Cystitis', 'Escherichia coli', 'Escherichia coli Infections', 'Female', 'Genotype', 'Humans', 'Male', 'Phylogeny', 'Urinary Bladder, Neurogenic', 'Urinary Tract Infections', 'Virulence Factors']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,559,622 | Does pTEN loss predict for response to RAD001 ( Everolimus ) in a glioblastoma orthotopic xenograft test panel? | {
"contexts": [
"Hyperactivation of the phosphatidylinositol 3-kinase/Akt signaling through disruption of PTEN function is common in glioblastoma multiforme, and these genetic changes are predicted to enhance sensitivity to mammalian target of rapamycin (mTOR) inhibitors such as RAD001 (everolimus).",
"To test whether PTEN loss could be used as a predictive marker for mTOR inhibitor sensitivity, the response of 17 serially transplantable glioblastoma multiforme xenografts was evaluated in an orthotopic therapy evaluation model. Of these 17 xenograft lines, 7 have either genomic deletion or mutation of PTEN.",
"Consistent with activation of Akt signaling, there was a good correlation between loss of PTEN function and elevated levels of Akt phosphorylation. However, of the 7 lines with disrupted PTEN function, only 1 tumor line (GBM10) was significantly sensitive to RAD001 therapy (25% prolongation in median survival), whereas 1 of 10 xenograft lines with wild-type PTEN was significantly sensitive to RAD001 (GS22; 34% prolongation in survival). Relative to placebo, 5 days of RAD001 treatment was associated with a marked 66% reduction in the MIB1 proliferation index in the sensitive GBM10 line (deleted PTEN) compared with a 25% and 7% reduction in MIB1 labeling index in the insensitive GBM14 (mutant PTEN) and GBM15 (wild-type PTEN) lines, respectively. Consistent with a cytostatic antitumor effect, bioluminescent imaging of luciferase-transduced intracranial GBM10 xenografts showed slowed tumor growth without significant tumor regression during RAD001 therapy."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Antineoplastic Agents",
"Apoptosis",
"Brain Neoplasms",
"Cell Proliferation",
"ErbB Receptors",
"Everolimus",
"Glioblastoma",
"Humans",
"Mice",
"Mice, Nude",
"Neovascularization, Pathologic",
"PTEN Phosphohydrolase",
"Prognosis",
"Protein Kinases",
"Sirolimus",
"TOR Serine-Threonine Kinases",
"Transplantation, Heterotopic",
"Xenograft Model Antitumor Assays"
]
} | These data suggest that loss of PTEN function is insufficient to adequately predict responsiveness to mTOR inhibitors in glioblastoma multiforme. | no | [
{
"from": "human",
"value": "Question: Does pTEN loss predict for response to RAD001 ( Everolimus ) in a glioblastoma orthotopic xenograft test panel?\nContext: {'contexts': ['Hyperactivation of the phosphatidylinositol 3-kinase/Akt signaling through disruption of PTEN function is common in glioblastoma multiforme, and these genetic changes are predicted to enhance sensitivity to mammalian target of rapamycin (mTOR) inhibitors such as RAD001 (everolimus).', 'To test whether PTEN loss could be used as a predictive marker for mTOR inhibitor sensitivity, the response of 17 serially transplantable glioblastoma multiforme xenografts was evaluated in an orthotopic therapy evaluation model. Of these 17 xenograft lines, 7 have either genomic deletion or mutation of PTEN.', 'Consistent with activation of Akt signaling, there was a good correlation between loss of PTEN function and elevated levels of Akt phosphorylation. However, of the 7 lines with disrupted PTEN function, only 1 tumor line (GBM10) was significantly sensitive to RAD001 therapy (25% prolongation in median survival), whereas 1 of 10 xenograft lines with wild-type PTEN was significantly sensitive to RAD001 (GS22; 34% prolongation in survival). Relative to placebo, 5 days of RAD001 treatment was associated with a marked 66% reduction in the MIB1 proliferation index in the sensitive GBM10 line (deleted PTEN) compared with a 25% and 7% reduction in MIB1 labeling index in the insensitive GBM14 (mutant PTEN) and GBM15 (wild-type PTEN) lines, respectively. Consistent with a cytostatic antitumor effect, bioluminescent imaging of luciferase-transduced intracranial GBM10 xenografts showed slowed tumor growth without significant tumor regression during RAD001 therapy.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Antineoplastic Agents', 'Apoptosis', 'Brain Neoplasms', 'Cell Proliferation', 'ErbB Receptors', 'Everolimus', 'Glioblastoma', 'Humans', 'Mice', 'Mice, Nude', 'Neovascularization, Pathologic', 'PTEN Phosphohydrolase', 'Prognosis', 'Protein Kinases', 'Sirolimus', 'TOR Serine-Threonine Kinases', 'Transplantation, Heterotopic', 'Xenograft Model Antitumor Assays']}"
},
{
"from": "gpt",
"value": "Answer: no"
}
]
|
18,559,621 | Is dNA-dependent protein kinase a therapeutic target and an indicator of poor prognosis in B-cell chronic lymphocytic leukemia? | {
"contexts": [
"del(17p), del(11q), and associated p53 dysfunction predict for short survival and chemoresistance in B-cell chronic lymphocytic leukemia (CLL). DNA-dependent protein kinase (DNA-PK) is activated by DNA damage and mediates DNA double-strand break repair. We hypothesized that inhibiting DNA-PK would sensitize CLL cells to drug-induced DNA damage and that this approach could increase the therapeutic index of agents used to treat CLL.",
"Fifty-four CLL cases were characterized for poor prognosis markers [del(17p), del(11q), CD38, and ZAP-70]. In selected cases, DNA-PK catalytic subunit (DNA-PKcs) expression and activity and p53 function were also measured. Ex vivo viability assays established sensitivity to fludarabine and chlorambucil and also tested the ability of a novel DNA-PK inhibitor (NU7441) to sensitize CLL cells to these drugs. The effects of NU7441 on fludarabine-induced DNA damage repair were also assessed (Comet assays and detection of gammaH2AX).",
"DNA-PKcs levels correlated with DNA-PK activity and varied 50-fold between cases but were consistently higher in del(17p) (P = 0.01) and del(11q) cases. NU7441 sensitized CLL cells to chlorambucil and fludarabine, including cases with del(17p), del(11q), p53 dysfunction, or high levels of DNA-PKcs. NU7441 increased fludarabine-induced double-strand breaks and abrogated drug-induced autophosphorylation of DNA-PKcs at Ser2056. High DNA-PK levels predicted for reduced treatment-free interval."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Aged, 80 and over",
"Biomarkers, Tumor",
"Chromones",
"DNA-Activated Protein Kinase",
"Drug Delivery Systems",
"Drug Evaluation, Preclinical",
"Drug Resistance, Neoplasm",
"Female",
"Humans",
"Leukemia, Lymphocytic, Chronic, B-Cell",
"Male",
"Middle Aged",
"Morpholines",
"Prognosis",
"Tumor Cells, Cultured"
]
} | These data validate the concept of targeting DNA-PKcs in poor risk CLL, and demonstrate a mechanistic rationale for use of a DNA-PK inhibitor. The novel observation that DNA-PKcs is overexpressed in del(17p) and del(11q) cases indicates that DNA-PK may contribute to disease progression in CLL. | yes | [
{
"from": "human",
"value": "Question: Is dNA-dependent protein kinase a therapeutic target and an indicator of poor prognosis in B-cell chronic lymphocytic leukemia?\nContext: {'contexts': ['del(17p), del(11q), and associated p53 dysfunction predict for short survival and chemoresistance in B-cell chronic lymphocytic leukemia (CLL). DNA-dependent protein kinase (DNA-PK) is activated by DNA damage and mediates DNA double-strand break repair. We hypothesized that inhibiting DNA-PK would sensitize CLL cells to drug-induced DNA damage and that this approach could increase the therapeutic index of agents used to treat CLL.', 'Fifty-four CLL cases were characterized for poor prognosis markers [del(17p), del(11q), CD38, and ZAP-70]. In selected cases, DNA-PK catalytic subunit (DNA-PKcs) expression and activity and p53 function were also measured. Ex vivo viability assays established sensitivity to fludarabine and chlorambucil and also tested the ability of a novel DNA-PK inhibitor (NU7441) to sensitize CLL cells to these drugs. The effects of NU7441 on fludarabine-induced DNA damage repair were also assessed (Comet assays and detection of gammaH2AX).', 'DNA-PKcs levels correlated with DNA-PK activity and varied 50-fold between cases but were consistently higher in del(17p) (P = 0.01) and del(11q) cases. NU7441 sensitized CLL cells to chlorambucil and fludarabine, including cases with del(17p), del(11q), p53 dysfunction, or high levels of DNA-PKcs. NU7441 increased fludarabine-induced double-strand breaks and abrogated drug-induced autophosphorylation of DNA-PKcs at Ser2056. High DNA-PK levels predicted for reduced treatment-free interval.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Aged, 80 and over', 'Biomarkers, Tumor', 'Chromones', 'DNA-Activated Protein Kinase', 'Drug Delivery Systems', 'Drug Evaluation, Preclinical', 'Drug Resistance, Neoplasm', 'Female', 'Humans', 'Leukemia, Lymphocytic, Chronic, B-Cell', 'Male', 'Middle Aged', 'Morpholines', 'Prognosis', 'Tumor Cells, Cultured']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,568,479 | Is childhood caries still in force : a 15-year follow-up? | {
"contexts": [
"To examine changes in caries prevalence among 3 to 15-year-old adolescents.",
"Of 1582 eligible mothers, 1443 gave informed consent. Participating children and their parents were followed up continuously from 3 to 15 years of age in a pre-planned fashion and at regular intervals. Data on dental health status were obtained from 1066/1287 adolescents (82%) during regular clinical dental examinations.",
"Dentinal untreated caries (D) was seen among more than 26% of the adolescents at 15 years of age. Altogether, 4.9 carious teeth surfaces were affected in each case (mean). Close to 18% of the adolescents (186/1066) had poor dental health (DMFT was 5 or more) and 26% (271/1066) had DMFS 5 or more."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Age Distribution",
"Child",
"Child, Preschool",
"Cohort Studies",
"Dental Caries",
"Dental Health Surveys",
"Female",
"Finland",
"Follow-Up Studies",
"Humans",
"Male",
"Population Surveillance",
"Prevalence"
]
} | Dental caries continues to constitute an increasing challenge in dental health care: any caries at 3, 5, 7, or 10 years of age was a predictor of poor dental health at 15 years of age. | yes | [
{
"from": "human",
"value": "Question: Is childhood caries still in force : a 15-year follow-up?\nContext: {'contexts': ['To examine changes in caries prevalence among 3 to 15-year-old adolescents.', 'Of 1582 eligible mothers, 1443 gave informed consent. Participating children and their parents were followed up continuously from 3 to 15 years of age in a pre-planned fashion and at regular intervals. Data on dental health status were obtained from 1066/1287 adolescents (82%) during regular clinical dental examinations.', 'Dentinal untreated caries (D) was seen among more than 26% of the adolescents at 15 years of age. Altogether, 4.9 carious teeth surfaces were affected in each case (mean). Close to 18% of the adolescents (186/1066) had poor dental health (DMFT was 5 or more) and 26% (271/1066) had DMFS 5 or more.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Age Distribution', 'Child', 'Child, Preschool', 'Cohort Studies', 'Dental Caries', 'Dental Health Surveys', 'Female', 'Finland', 'Follow-Up Studies', 'Humans', 'Male', 'Population Surveillance', 'Prevalence']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,572,870 | Does [ Longbixiao capsule reduce expressions of TGF-beta1 and Smoothelin in human prostatic stromal cells cultured in vitro ]? | {
"contexts": [
"To investigate the effects of the Chinese herbal medicine of Longbixiao (LBX) Capsule on the expressions of TGF-beta1 and Smoothelin in human prostatic stromal cells cultured in vitro.",
"Blood serum medicated with LBX was incubated with the stromal cells isolated from men with benign prostatic hyperplasia (BPH) and cultured in vitro. The mRNA expression levels of TGF-beta1 and Smoothelin were detected by real-time RT-PCR and other relevant techniques.",
"In the high and low concentration groups, the gene relative expressions of TGF-beta1 were (0.158 +/- 0.020) and (0.169 +/- 0.020) , while those of Smoothelin were (0.035 +/- 0.007) and (0.036 +/- 0.007) respectively, both significantly decreased in comparison with the control group(P < 0.01)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Capsules",
"Cells, Cultured",
"Cytoskeletal Proteins",
"Dose-Response Relationship, Drug",
"Drugs, Chinese Herbal",
"Gene Expression",
"Humans",
"Male",
"Muscle Proteins",
"Prostatic Hyperplasia",
"Rabbits",
"Reverse Transcriptase Polymerase Chain Reaction",
"Serum",
"Stromal Cells",
"Transforming Growth Factor beta1"
]
} | LBX reduces the mRNA expressions of TGF-beta1 and Smoothelin in human prostatic stromal cells and can be used in the treatment of BPH. | yes | [
{
"from": "human",
"value": "Question: Does [ Longbixiao capsule reduce expressions of TGF-beta1 and Smoothelin in human prostatic stromal cells cultured in vitro ]?\nContext: {'contexts': ['To investigate the effects of the Chinese herbal medicine of Longbixiao (LBX) Capsule on the expressions of TGF-beta1 and Smoothelin in human prostatic stromal cells cultured in vitro.', 'Blood serum medicated with LBX was incubated with the stromal cells isolated from men with benign prostatic hyperplasia (BPH) and cultured in vitro. The mRNA expression levels of TGF-beta1 and Smoothelin were detected by real-time RT-PCR and other relevant techniques.', 'In the high and low concentration groups, the gene relative expressions of TGF-beta1 were (0.158 +/- 0.020) and (0.169 +/- 0.020) , while those of Smoothelin were (0.035 +/- 0.007) and (0.036 +/- 0.007) respectively, both significantly decreased in comparison with the control group(P < 0.01).'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Capsules', 'Cells, Cultured', 'Cytoskeletal Proteins', 'Dose-Response Relationship, Drug', 'Drugs, Chinese Herbal', 'Gene Expression', 'Humans', 'Male', 'Muscle Proteins', 'Prostatic Hyperplasia', 'Rabbits', 'Reverse Transcriptase Polymerase Chain Reaction', 'Serum', 'Stromal Cells', 'Transforming Growth Factor beta1']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,545,662 | Does intestinal colonization of IL-2 deficient mice with non-colitogenic B. vulgatus prevent DC maturation and T-cell polarization? | {
"contexts": [
"IL-2 deficient (IL-2(-/-)) mice mono-colonized with E. coli mpk develop colitis whereas IL-2(-/-)-mice mono-colonized with B. vulgatus mpk do not and are even protected from E. coli mpk induced colitis.",
"We investigated if mono-colonization with E. coli mpk or B. vulgatus mpk differentially modulates distribution, activation and maturation of intestinal lamina propria (LP) dendritic cells (DC). LP DC in mice mono-colonized with protective B. vulgatus mpk or co-colonized with E. coli mpk/B. vulgatus mpk featured a semi-mature LP DC phenotype (CD40(lo)CD80(lo)MHC-II(hi)) whereas mono-colonization with colitogenic E. coli mpk induced LP DC activation and maturation prior to onset of colitis. Accordingly, chemokine receptor (CCR) 7 surface expression was more strikingly enhanced in mesenteric lymph node DC from E. coli mpk than B. vulgatus mpk mono- or co-colonized mice. Mature but not semi-mature LP DC promoted Th1 polarization. As B. vulgatus mpk promotes differentiation of semi-mature DC presumably by IL-6, mRNA and protein expression of IL-6 was investigated in LP DC. The data demonstrated that IL-6 mRNA and protein was increased in LP DC of B. vulgatus mpk as compared to E. coli mpk mono-colonized IL-2(-/-)-mice. The B. vulgatus mpk mediated suppression of CCR7 expression and DC migration was abolished in IL-6(-/-)-DC in vitro."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Animals",
"Bacillus",
"Dendritic Cells",
"Interleukin-2",
"Interleukin-6",
"Intestines",
"Lymphocyte Activation",
"Mice",
"Mice, Inbred C57BL",
"Mice, Knockout",
"T-Lymphocytes",
"Tumor Necrosis Factor-alpha"
]
} | From this data we conclude that the B. vulgatus triggered IL-6 secretion by LP DC in absence of proinflammatory cytokines such as IL-12 or TNF-alpha induces a semi-mature LP DC phenotype, which might prevent T-cell activation and thereby the induction of colitis in IL-2(-/-)-mice. The data provide new evidence that IL-6 might act as an immune regulatory cytokine in the mucosa by targeting intestinal DC. | yes | [
{
"from": "human",
"value": "Question: Does intestinal colonization of IL-2 deficient mice with non-colitogenic B. vulgatus prevent DC maturation and T-cell polarization?\nContext: {'contexts': ['IL-2 deficient (IL-2(-/-)) mice mono-colonized with E. coli mpk develop colitis whereas IL-2(-/-)-mice mono-colonized with B. vulgatus mpk do not and are even protected from E. coli mpk induced colitis.', 'We investigated if mono-colonization with E. coli mpk or B. vulgatus mpk differentially modulates distribution, activation and maturation of intestinal lamina propria (LP) dendritic cells (DC). LP DC in mice mono-colonized with protective B. vulgatus mpk or co-colonized with E. coli mpk/B. vulgatus mpk featured a semi-mature LP DC phenotype (CD40(lo)CD80(lo)MHC-II(hi)) whereas mono-colonization with colitogenic E. coli mpk induced LP DC activation and maturation prior to onset of colitis. Accordingly, chemokine receptor (CCR) 7 surface expression was more strikingly enhanced in mesenteric lymph node DC from E. coli mpk than B. vulgatus mpk mono- or co-colonized mice. Mature but not semi-mature LP DC promoted Th1 polarization. As B. vulgatus mpk promotes differentiation of semi-mature DC presumably by IL-6, mRNA and protein expression of IL-6 was investigated in LP DC. The data demonstrated that IL-6 mRNA and protein was increased in LP DC of B. vulgatus mpk as compared to E. coli mpk mono-colonized IL-2(-/-)-mice. The B. vulgatus mpk mediated suppression of CCR7 expression and DC migration was abolished in IL-6(-/-)-DC in vitro.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Animals', 'Bacillus', 'Dendritic Cells', 'Interleukin-2', 'Interleukin-6', 'Intestines', 'Lymphocyte Activation', 'Mice', 'Mice, Inbred C57BL', 'Mice, Knockout', 'T-Lymphocytes', 'Tumor Necrosis Factor-alpha']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,556,623 | Does triiodo-L-thyronine rapidly stimulate alveolar fluid clearance in normal and hyperoxia-injured lungs? | {
"contexts": [
"Edema fluid resorption is critical for gas exchange and requires active epithelial ion transport by Na, K-ATPase and other ion transport proteins.",
"In this study, we sought to determine if alveolar fluid clearance (AFC) is stimulated by 3,3',5 triiodo-L-thyronine (T(3)).",
"AFC was measured in in situ ventilated lungs and ex vivo isolated lungs by instilling isosmolar 5% bovine serum albumin solution with fluorescein-labeled albumin tracer and measuring the change in fluorescein isothiocyanate-albumin concentration over time.",
"Systemic treatment with intraperitoneal injections of T(3) for 3 consecutive days increased AFC by 52.7% compared with phosphate-buffered saline-injected control rats. Membranes prepared from alveolar epithelial cells from T(3)-treated rats had higher Na, K-ATPase hydrolytic activity. T(3) (10(-6) M), but not reverse T(3) (3,3',5' triiodo-L-thyronine), applied to the alveolar space increased AFC by 31.8% within 1.5 hours. A 61.5% increase in AFC also occurred by airspace instillation of T(3) in ex vivo isolated lungs, suggesting a direct effect of T(3) on the alveolar epithelium. Exposure of rats to an oxygen concentration of greater than 95% for 60 hours increased wet-to-dry lung weights and decreased AFC, whereas the expression of thyroid receptor was not markedly changed. Airspace T(3) rapidly restored the AFC in rat lungs with hyperoxia-induced lung injury."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Cells, Cultured",
"Injections, Intraperitoneal",
"Male",
"Pulmonary Edema",
"Rats",
"Rats, Sprague-Dawley",
"Respiratory Distress Syndrome, Adult",
"Respiratory Mucosa",
"Sodium-Potassium-Exchanging ATPase",
"Triiodothyronine"
]
} | Airspace T(3) rapidly stimulates AFC by direct effects on the alveolar epithelium in rat lungs with and without lung injury. | yes | [
{
"from": "human",
"value": "Question: Does triiodo-L-thyronine rapidly stimulate alveolar fluid clearance in normal and hyperoxia-injured lungs?\nContext: {'contexts': ['Edema fluid resorption is critical for gas exchange and requires active epithelial ion transport by Na, K-ATPase and other ion transport proteins.', \"In this study, we sought to determine if alveolar fluid clearance (AFC) is stimulated by 3,3',5 triiodo-L-thyronine (T(3)).\", 'AFC was measured in in situ ventilated lungs and ex vivo isolated lungs by instilling isosmolar 5% bovine serum albumin solution with fluorescein-labeled albumin tracer and measuring the change in fluorescein isothiocyanate-albumin concentration over time.', \"Systemic treatment with intraperitoneal injections of T(3) for 3 consecutive days increased AFC by 52.7% compared with phosphate-buffered saline-injected control rats. Membranes prepared from alveolar epithelial cells from T(3)-treated rats had higher Na, K-ATPase hydrolytic activity. T(3) (10(-6) M), but not reverse T(3) (3,3',5' triiodo-L-thyronine), applied to the alveolar space increased AFC by 31.8% within 1.5 hours. A 61.5% increase in AFC also occurred by airspace instillation of T(3) in ex vivo isolated lungs, suggesting a direct effect of T(3) on the alveolar epithelium. Exposure of rats to an oxygen concentration of greater than 95% for 60 hours increased wet-to-dry lung weights and decreased AFC, whereas the expression of thyroid receptor was not markedly changed. Airspace T(3) rapidly restored the AFC in rat lungs with hyperoxia-induced lung injury.\"], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Cells, Cultured', 'Injections, Intraperitoneal', 'Male', 'Pulmonary Edema', 'Rats', 'Rats, Sprague-Dawley', 'Respiratory Distress Syndrome, Adult', 'Respiratory Mucosa', 'Sodium-Potassium-Exchanging ATPase', 'Triiodothyronine']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,570,928 | Does valproic acid induce Notch1 signaling in small cell lung cancer cells? | {
"contexts": [
"Small cell lung cancer (SCLC) is an aggressive malignancy. Current treatments yield dismal survival rates. We have previously demonstrated that histone deacetylase (HDAC) inhibitors can inhibit neuroendocrine tumor growth. Activation of the Notch1 signaling pathway also impairs SCLC cell viability. In this study, we investigated the ability of the HDAC inhibitor valproic acid (VPA) to activate Notch1 signaling and inhibit proliferation in SCLC cells.",
"DMS53 human SCLC cells were treated with VPA (0-10 mM) for 2 d. Light microscopy was used to examine changes in cell morphology. Western analysis was performed using antibodies against various Notch1 pathway proteins to assess Notch1 activation. Additionally, immunoblotting was performed for two neuroendocrine tumor markers, chromogranin A and achaete-scute complex-like 1. Finally, a cell proliferation assay was used to measure the effects of VPA on SCLC growth over 8 d.",
"After treatment with VPA, DMS53 cells underwent dramatic changes in morphology. VPA induced expression of the full-length and active forms of Notch1 protein. Furthermore, VPA suppressed levels of neuroendocrine tumor markers chromogranin A and ASLC-1. Importantly, VPA treatment led to dose-dependent inhibition of SCLC cell proliferation."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Antineoplastic Agents",
"Basic Helix-Loop-Helix Transcription Factors",
"Biomarkers, Tumor",
"Blotting, Western",
"Carcinoma, Small Cell",
"Cell Line, Tumor",
"Cell Proliferation",
"Chromogranin A",
"Down-Regulation",
"Gene Expression Regulation, Neoplastic",
"Humans",
"Lung Neoplasms",
"Phenotype",
"Receptor, Notch1",
"Signal Transduction",
"Valproic Acid"
]
} | The HDAC inhibitor VPA activates Notch1 signaling in SCLC cells. VPA induces changes in cell morphology and suppresses neuroendocrine tumor markers, indicating a change in phenotype. Additionally, VPA profoundly inhibits SCLC cell growth. These results suggest that VPA has potential as a novel therapeutic agent for SCLC. | yes | [
{
"from": "human",
"value": "Question: Does valproic acid induce Notch1 signaling in small cell lung cancer cells?\nContext: {'contexts': ['Small cell lung cancer (SCLC) is an aggressive malignancy. Current treatments yield dismal survival rates. We have previously demonstrated that histone deacetylase (HDAC) inhibitors can inhibit neuroendocrine tumor growth. Activation of the Notch1 signaling pathway also impairs SCLC cell viability. In this study, we investigated the ability of the HDAC inhibitor valproic acid (VPA) to activate Notch1 signaling and inhibit proliferation in SCLC cells.', 'DMS53 human SCLC cells were treated with VPA (0-10 mM) for 2 d. Light microscopy was used to examine changes in cell morphology. Western analysis was performed using antibodies against various Notch1 pathway proteins to assess Notch1 activation. Additionally, immunoblotting was performed for two neuroendocrine tumor markers, chromogranin A and achaete-scute complex-like 1. Finally, a cell proliferation assay was used to measure the effects of VPA on SCLC growth over 8 d.', 'After treatment with VPA, DMS53 cells underwent dramatic changes in morphology. VPA induced expression of the full-length and active forms of Notch1 protein. Furthermore, VPA suppressed levels of neuroendocrine tumor markers chromogranin A and ASLC-1. Importantly, VPA treatment led to dose-dependent inhibition of SCLC cell proliferation.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Antineoplastic Agents', 'Basic Helix-Loop-Helix Transcription Factors', 'Biomarkers, Tumor', 'Blotting, Western', 'Carcinoma, Small Cell', 'Cell Line, Tumor', 'Cell Proliferation', 'Chromogranin A', 'Down-Regulation', 'Gene Expression Regulation, Neoplastic', 'Humans', 'Lung Neoplasms', 'Phenotype', 'Receptor, Notch1', 'Signal Transduction', 'Valproic Acid']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,570,927 | Does ischemic preconditioning of skeletal muscle mitigate remote injury and mortality? | {
"contexts": [
"Ischemic preconditioning (IPC) mitigates ischemia-reperfusion (I/R) injury in experimental models. However, the clinical significance of this protection has been unclear and a mortality reduction has not been previously reported in noncardiac models. This study examined the local and remote protection afforded by skeletal muscle IPC and sought to determine the significance of this protection on mortality.",
"Mice subjected to 2 h hindlimb ischemia/24 h reperfusion (standard I/R injury) were compared with those undergoing a regimen of two 20-min cycles of IPC followed by standard I/R injury. Local injury was assessed via gastrocnemius histology, and remote injury was evaluated via intestinal histology and pulmonary neutrophil infiltration (n = 7). Mortality was compared in parallel groups for 1 week (n = 6). Groups were analyzed using an unpaired Student's t-test for gastrocnemius and pulmonary injury, and a Mann-Whitney rank sum test for intestinal injury. Mortality differences were interpreted through a hazard ratio.",
"Significant protection was observed in preconditioned animals. There was a 35% local injury reduction in skeletal muscle (71.2% versus 46.0%, P < 0.01), a 50% reduction in remote intestinal injury (2.3 versus 1.1, P < 0.01), and a 43% reduction in remote pulmonary injury (14.9 versus 8.5, P < 0.01) compared with standard injury controls. Preconditioned animals were also significantly protected from mortality, demonstrating a 66.7% survival at 1 wk compared with 0% survival after standard injury alone (hazard ratio 0.20, 95% CI: 0.02-0.59)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Hindlimb",
"Ischemic Preconditioning",
"Male",
"Mice",
"Muscle, Skeletal",
"Reperfusion Injury"
]
} | We have developed a murine model of IPC that demonstrates local and remote protection against I/R injury, and exhibits significant mortality reduction. This model demonstrates the powerful effect of IPC on local and remote tissues and will facilitate further study of potential mechanisms and therapies. | yes | [
{
"from": "human",
"value": "Question: Does ischemic preconditioning of skeletal muscle mitigate remote injury and mortality?\nContext: {'contexts': ['Ischemic preconditioning (IPC) mitigates ischemia-reperfusion (I/R) injury in experimental models. However, the clinical significance of this protection has been unclear and a mortality reduction has not been previously reported in noncardiac models. This study examined the local and remote protection afforded by skeletal muscle IPC and sought to determine the significance of this protection on mortality.', \"Mice subjected to 2 h hindlimb ischemia/24 h reperfusion (standard I/R injury) were compared with those undergoing a regimen of two 20-min cycles of IPC followed by standard I/R injury. Local injury was assessed via gastrocnemius histology, and remote injury was evaluated via intestinal histology and pulmonary neutrophil infiltration (n = 7). Mortality was compared in parallel groups for 1 week (n = 6). Groups were analyzed using an unpaired Student's t-test for gastrocnemius and pulmonary injury, and a Mann-Whitney rank sum test for intestinal injury. Mortality differences were interpreted through a hazard ratio.\", 'Significant protection was observed in preconditioned animals. There was a 35% local injury reduction in skeletal muscle (71.2% versus 46.0%, P < 0.01), a 50% reduction in remote intestinal injury (2.3 versus 1.1, P < 0.01), and a 43% reduction in remote pulmonary injury (14.9 versus 8.5, P < 0.01) compared with standard injury controls. Preconditioned animals were also significantly protected from mortality, demonstrating a 66.7% survival at 1 wk compared with 0% survival after standard injury alone (hazard ratio 0.20, 95% CI: 0.02-0.59).'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Hindlimb', 'Ischemic Preconditioning', 'Male', 'Mice', 'Muscle, Skeletal', 'Reperfusion Injury']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,560,547 | Is ammonium-acetate sensed by gustatory and olfactory neurons in Caenorhabditis elegans? | {
"contexts": [
"Caenorhabditis elegans chemosensation has been successfully studied using behavioral assays that treat detection of volatile and water soluble chemicals as separate senses, analogous to smell and taste. However, considerable ambiguity has been associated with the attractive properties of the compound ammonium-acetate (NH(4)Ac). NH(4)Ac has been used in behavioral assays both as a chemosensory neutral compound and as an attractant.",
"Here we show that over a range of concentrations NH(4)Ac can be detected both as a water soluble attractant and as an odorant, and that ammonia and acetic acid individually act as olfactory attractants. We use genetic analysis to show that NaCl and NH(4)Ac sensation are mediated by separate pathways and that ammonium sensation depends on the cyclic nucleotide gated ion channel TAX-2/TAX-4, but acetate sensation does not. Furthermore we show that sodium-acetate (NaAc) and ammonium-chloride (NH(4)Cl) are not detected as Na(+) and Cl(-) specific stimuli, respectively."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Acetates",
"Animals",
"Behavior, Animal",
"Caenorhabditis elegans",
"Neurons",
"Olfactory Receptor Neurons",
"Taste"
]
} | These findings clarify the behavioral response of C. elegans to NH(4)Ac. The results should have an impact on the design and interpretation of chemosensory experiments studying detection and adaptation to soluble compounds in the nematode Caenorhabditis elegans. | yes | [
{
"from": "human",
"value": "Question: Is ammonium-acetate sensed by gustatory and olfactory neurons in Caenorhabditis elegans?\nContext: {'contexts': ['Caenorhabditis elegans chemosensation has been successfully studied using behavioral assays that treat detection of volatile and water soluble chemicals as separate senses, analogous to smell and taste. However, considerable ambiguity has been associated with the attractive properties of the compound ammonium-acetate (NH(4)Ac). NH(4)Ac has been used in behavioral assays both as a chemosensory neutral compound and as an attractant.', 'Here we show that over a range of concentrations NH(4)Ac can be detected both as a water soluble attractant and as an odorant, and that ammonia and acetic acid individually act as olfactory attractants. We use genetic analysis to show that NaCl and NH(4)Ac sensation are mediated by separate pathways and that ammonium sensation depends on the cyclic nucleotide gated ion channel TAX-2/TAX-4, but acetate sensation does not. Furthermore we show that sodium-acetate (NaAc) and ammonium-chloride (NH(4)Cl) are not detected as Na(+) and Cl(-) specific stimuli, respectively.'], 'labels': ['BACKGROUND', 'RESULTS'], 'meshes': ['Acetates', 'Animals', 'Behavior, Animal', 'Caenorhabditis elegans', 'Neurons', 'Olfactory Receptor Neurons', 'Taste']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,559,659 | Does rapamycin monotherapy in patients with type 1 diabetes modify CD4+CD25+FOXP3+ regulatory T-cells? | {
"contexts": [
"Rapamycin is an immunosuppressive drug currently used to prevent graft rejection in humans, which is considered permissive for tolerance induction. Rapamycin allows expansion of both murine and human naturally occurring CD4(+)CD25(+)FOXP3(+) T regulatory cells (nTregs), which are pivotal for the induction and maintenance of peripheral tolerance. Preclinical murine models have shown that rapamycin enhances nTreg proliferation and regulatory function also in vivo. Objective of this study was to assess whether rapamycin has in vivo effects on human nTregs.",
"nTreg numbers and function were examined in a unique set of patients with type 1 diabetes who underwent rapamycin monotherapy before islet transplantation.",
"We found that rapamycin monotherapy did not alter the frequency and functional features, namely proliferation and cytokine production, of circulating nTregs. However, nTregs isolated from type 1 diabetic patients under rapamycin treatment had an increased capability to suppress proliferation of CD4(+)CD25(-) effector T-cells compared with that before treatment."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"CD4 Antigens",
"CD4 Lymphocyte Count",
"Combined Modality Therapy",
"Diabetes Mellitus, Type 1",
"Female",
"Flow Cytometry",
"Forkhead Transcription Factors",
"Graft Rejection",
"Humans",
"Immunosuppressive Agents",
"Interleukin-2 Receptor alpha Subunit",
"Islets of Langerhans Transplantation",
"Male",
"Middle Aged",
"Preoperative Care",
"Sirolimus",
"T-Lymphocytes, Regulatory"
]
} | These findings demonstrate that rapamycin directly affects human nTreg function in vivo, which consists of refitting their suppressive activity, whereas it does not directly change effector T-cell function. | yes | [
{
"from": "human",
"value": "Question: Does rapamycin monotherapy in patients with type 1 diabetes modify CD4+CD25+FOXP3+ regulatory T-cells?\nContext: {'contexts': ['Rapamycin is an immunosuppressive drug currently used to prevent graft rejection in humans, which is considered permissive for tolerance induction. Rapamycin allows expansion of both murine and human naturally occurring CD4(+)CD25(+)FOXP3(+) T regulatory cells (nTregs), which are pivotal for the induction and maintenance of peripheral tolerance. Preclinical murine models have shown that rapamycin enhances nTreg proliferation and regulatory function also in vivo. Objective of this study was to assess whether rapamycin has in vivo effects on human nTregs.', 'nTreg numbers and function were examined in a unique set of patients with type 1 diabetes who underwent rapamycin monotherapy before islet transplantation.', 'We found that rapamycin monotherapy did not alter the frequency and functional features, namely proliferation and cytokine production, of circulating nTregs. However, nTregs isolated from type 1 diabetic patients under rapamycin treatment had an increased capability to suppress proliferation of CD4(+)CD25(-) effector T-cells compared with that before treatment.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adult', 'CD4 Antigens', 'CD4 Lymphocyte Count', 'Combined Modality Therapy', 'Diabetes Mellitus, Type 1', 'Female', 'Flow Cytometry', 'Forkhead Transcription Factors', 'Graft Rejection', 'Humans', 'Immunosuppressive Agents', 'Interleukin-2 Receptor alpha Subunit', 'Islets of Langerhans Transplantation', 'Male', 'Middle Aged', 'Preoperative Care', 'Sirolimus', 'T-Lymphocytes, Regulatory']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,567,547 | Does the RR genotype of codon 72 of p53 gene reduce the development of intestinal metaplasia? | {
"contexts": [
"Mutations of p53 gene can contribute to the development of gastric cancer. Our aims were to evaluate the premalignant gastric intestinal metaplasia-related p53 alterations, using and comparing capillary sequencing and p53 resequencing chip in gastric biopsy and peripheral blood samples. Furthermore we examined the effect of p53 polymorphism on the protein expression level.",
"Deoxyribonucleic acid was extracted from antral gastric biopsy samples of 50 intestinal metaplasia patients (27 Helicobacter pylori positive, 23 H. pylori negative) and 51 controls (all H. pylori negative). Exon 4 of p53 gene was examined by capillary sequencing (CS). From 7 intestinal metaplasia patients extra deoxyribonucleic acid samples were extracted from blood and from the corpus and from the antrum of the stomach and 5 additional exons were examined by CS and 10 with GeneChip p53 Assay (Affymetrix). In 19 patients p53 immunohistochemistry was performed.",
"RR genotype on codon 72 was found to significantly (p=0.0087) reduce the chance of intestinal metaplasia in H. pylori positive patients as compared to the normal controls. The p53 alterations were identical in antral, corpus and blood samples. The p53 protein expression was in significant correlation with the genetic alterations. CS and chip method-based sequencing results were not in correlation."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Biopsy",
"Case-Control Studies",
"Codon",
"DNA",
"Electrophoresis, Capillary",
"Exons",
"Gastric Mucosa",
"Gene Expression Profiling",
"Gene Frequency",
"Genes, p53",
"Genotype",
"Helicobacter pylori",
"Humans",
"Immunohistochemistry",
"Metaplasia",
"Polymerase Chain Reaction",
"Polymorphism, Genetic",
"Precancerous Conditions",
"Sequence Analysis, DNA",
"Stomach",
"Tumor Suppressor Protein p53"
]
} | According to our results RR genotype decreases the incidence of IM. The genetic background is reflected in the expression of p53 protein. Chip method-based deoxyribonucleic acid sequence data need careful confirmation. | yes | [
{
"from": "human",
"value": "Question: Does the RR genotype of codon 72 of p53 gene reduce the development of intestinal metaplasia?\nContext: {'contexts': ['Mutations of p53 gene can contribute to the development of gastric cancer. Our aims were to evaluate the premalignant gastric intestinal metaplasia-related p53 alterations, using and comparing capillary sequencing and p53 resequencing chip in gastric biopsy and peripheral blood samples. Furthermore we examined the effect of p53 polymorphism on the protein expression level.', 'Deoxyribonucleic acid was extracted from antral gastric biopsy samples of 50 intestinal metaplasia patients (27 Helicobacter pylori positive, 23 H. pylori negative) and 51 controls (all H. pylori negative). Exon 4 of p53 gene was examined by capillary sequencing (CS). From 7 intestinal metaplasia patients extra deoxyribonucleic acid samples were extracted from blood and from the corpus and from the antrum of the stomach and 5 additional exons were examined by CS and 10 with GeneChip p53 Assay (Affymetrix). In 19 patients p53 immunohistochemistry was performed.', 'RR genotype on codon 72 was found to significantly (p=0.0087) reduce the chance of intestinal metaplasia in H. pylori positive patients as compared to the normal controls. The p53 alterations were identical in antral, corpus and blood samples. The p53 protein expression was in significant correlation with the genetic alterations. CS and chip method-based sequencing results were not in correlation.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Biopsy', 'Case-Control Studies', 'Codon', 'DNA', 'Electrophoresis, Capillary', 'Exons', 'Gastric Mucosa', 'Gene Expression Profiling', 'Gene Frequency', 'Genes, p53', 'Genotype', 'Helicobacter pylori', 'Humans', 'Immunohistochemistry', 'Metaplasia', 'Polymerase Chain Reaction', 'Polymorphism, Genetic', 'Precancerous Conditions', 'Sequence Analysis, DNA', 'Stomach', 'Tumor Suppressor Protein p53']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,546,066 | Do factors for accessing a medical home vary among CSHCN from different levels of socioeconomic status? | {
"contexts": [
"The purpose of this research study was to identify factors that are associated with receiving care in a medical home for children with special health care needs (CSHCN) and to identify how these factors vary among different socioeconomic levels.",
"Data were obtained from the National Survey of Children with Special Health Care Needs, 2000-2002. Access to a medical home was derived using an algorithm. This survey analysis also included demographic characteristics, geographical location of household, severity of condition, and social factors. Multiple logistic regression models were constructed for socioeconomic status (SES) levels defined by federal poverty level (FPL): <133%; 133-199%; 200-299%; > or =300%.",
"Age group was significant in all but the 200-299% of FPL stratum. Severity of condition was significant in all strata. Race was significant in all but the > or =300% stratum. Maternal education was borderline significant in the lowest and highest strata. Insurance type/status was significant in all but the 133-199% of FPL stratum. Geographical location was significant in the lowest and highest strata. The language of the interview was only significant in the lowest stratum. The relationship of the respondent to the child was significant in the middle two strata. The total number of adults in the household was significant in the highest stratum, and the total number of children in the household was significant in the 200-299% of FPL stratum."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Child",
"Child, Preschool",
"Disabled Children",
"Female",
"Health Care Surveys",
"Health Services Accessibility",
"Humans",
"Infant",
"Infant, Newborn",
"Logistic Models",
"Male",
"Maternal-Child Health Centers",
"Patient-Centered Care",
"Social Class"
]
} | Factors affecting access to a medical home differed among socioeconomic groups. Future research should explore the CSHCN population by income groups to better serve this population. | yes | [
{
"from": "human",
"value": "Question: Do factors for accessing a medical home vary among CSHCN from different levels of socioeconomic status?\nContext: {'contexts': ['The purpose of this research study was to identify factors that are associated with receiving care in a medical home for children with special health care needs (CSHCN) and to identify how these factors vary among different socioeconomic levels.', 'Data were obtained from the National Survey of Children with Special Health Care Needs, 2000-2002. Access to a medical home was derived using an algorithm. This survey analysis also included demographic characteristics, geographical location of household, severity of condition, and social factors. Multiple logistic regression models were constructed for socioeconomic status (SES) levels defined by federal poverty level (FPL): <133%; 133-199%; 200-299%; > or =300%.', 'Age group was significant in all but the 200-299% of FPL stratum. Severity of condition was significant in all strata. Race was significant in all but the > or =300% stratum. Maternal education was borderline significant in the lowest and highest strata. Insurance type/status was significant in all but the 133-199% of FPL stratum. Geographical location was significant in the lowest and highest strata. The language of the interview was only significant in the lowest stratum. The relationship of the respondent to the child was significant in the middle two strata. The total number of adults in the household was significant in the highest stratum, and the total number of children in the household was significant in the 200-299% of FPL stratum.'], 'labels': ['OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Child', 'Child, Preschool', 'Disabled Children', 'Female', 'Health Care Surveys', 'Health Services Accessibility', 'Humans', 'Infant', 'Infant, Newborn', 'Logistic Models', 'Male', 'Maternal-Child Health Centers', 'Patient-Centered Care', 'Social Class']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,564,112 | Does 24-Hour colonic manometry in pediatric slow transit constipation show significant reductions in antegrade propagation? | {
"contexts": [
"The physiological basis of slow transit constipation (STC) in children remains poorly understood. We wished to examine pan-colonic motility in a group of children with severe chronic constipation refractory to conservative therapy.",
"We performed 24 h pan-colonic manometry in 18 children (13 boys, 11.6 +/- 0.9 yr, range 6.6-18.7 yr) with scintigraphically proven STC. A water-perfused, balloon tipped, 8-channel, silicone catheter with a 7.5 cm intersidehole distance was introduced through a previously formed appendicostomy. Comparison data were obtained from nasocolonic motility studies in 16 healthy young adult controls and per-appendicostomy motility studies in eight constipated children with anorectal retention and/or normal transit on scintigraphy (non-STC).",
"Antegrade propagating sequences (PS) were significantly less frequent (P < 0.01) in subjects with STC (29 +/- 4 per 24 h) compared to adult (53 +/- 4 per 24 h) and non-STC (70 +/- 14 per 24 h) subjects. High amplitude propagating sequences (HAPS) were of a normal frequency in STC subjects. Retrograde propagating sequences were significantly more frequent (P < 0.05) in non-STC subjects compared to STC and adult subjects. High amplitude retrograde propagating sequences were only identified in the STC and non-STC pediatric groups. The normal increase in motility index associated with waking and ingestion of a meal was absent in STC subjects."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Adult",
"Age Factors",
"Case-Control Studies",
"Child",
"Chronic Disease",
"Colon",
"Constipation",
"Female",
"Gastrointestinal Transit",
"Humans",
"Male",
"Manometry",
"Monitoring, Ambulatory",
"Myoelectric Complex, Migrating",
"Radiography",
"Radionuclide Imaging",
"Walking"
]
} | Prolonged pancolonic manometry in children with STC showed significant impairment in antegrade propagating motor activity and failure to respond to normal physiological stimuli. Despite this, HAPS occurred with normal frequency. These findings suggest significant clinical differences between STC in children and adults. | yes | [
{
"from": "human",
"value": "Question: Does 24-Hour colonic manometry in pediatric slow transit constipation show significant reductions in antegrade propagation?\nContext: {'contexts': ['The physiological basis of slow transit constipation (STC) in children remains poorly understood. We wished to examine pan-colonic motility in a group of children with severe chronic constipation refractory to conservative therapy.', 'We performed 24 h pan-colonic manometry in 18 children (13 boys, 11.6 +/- 0.9 yr, range 6.6-18.7 yr) with scintigraphically proven STC. A water-perfused, balloon tipped, 8-channel, silicone catheter with a 7.5 cm intersidehole distance was introduced through a previously formed appendicostomy. Comparison data were obtained from nasocolonic motility studies in 16 healthy young adult controls and per-appendicostomy motility studies in eight constipated children with anorectal retention and/or normal transit on scintigraphy (non-STC).', 'Antegrade propagating sequences (PS) were significantly less frequent (P < 0.01) in subjects with STC (29 +/- 4 per 24 h) compared to adult (53 +/- 4 per 24 h) and non-STC (70 +/- 14 per 24 h) subjects. High amplitude propagating sequences (HAPS) were of a normal frequency in STC subjects. Retrograde propagating sequences were significantly more frequent (P < 0.05) in non-STC subjects compared to STC and adult subjects. High amplitude retrograde propagating sequences were only identified in the STC and non-STC pediatric groups. The normal increase in motility index associated with waking and ingestion of a meal was absent in STC subjects.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Adolescent', 'Adult', 'Age Factors', 'Case-Control Studies', 'Child', 'Chronic Disease', 'Colon', 'Constipation', 'Female', 'Gastrointestinal Transit', 'Humans', 'Male', 'Manometry', 'Monitoring, Ambulatory', 'Myoelectric Complex, Migrating', 'Radiography', 'Radionuclide Imaging', 'Walking']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,552,575 | Are hypokalemia and hypothermia associated with 30-day mortality in patients with acute paraquat poisoning? | {
"contexts": [
"Clinical predictors associated with acute paraquat (PQ) poisoning have not been systematically studied.",
"To identify independent predictors of death in patients with acute PQ poisoning.",
"This is a retrospective study executed in the emergency department of a university hospital. One hundred three consecutive patients poisoned with PQ between January 1999 and December 2004 were enrolled. Urine PQ concentration, electrolyte and renal function, detailed history, and Acute Physiology and Chronic Health Evaluation II were extracted from medical records. The outcome measure was 30-day mortality. Multivariate analysis was done by Cox-proportional hazard regression model. Receiver operating characteristics area under the curve was calculated for selected predictors.",
"The crude 30-day mortality was 67.9% (70 of 103). Independent predictors of death were acute renal failure (hazard ratio, 3.53; 95% confidence interval, 1.97-6.32), hypokalemia (2.07, 1.21-3.51), hypothermia (2.91, 1.67-5.07), suicide (2.11, 1.04-4.29), and self-reported ingested dose (2.06, 1.38-3.06). The receiver operating characteristics area under the curve of serum potassium concentrations, maximal urine PQ concentrations, and Acute Physiology and Chronic Health Evaluation II scores were 0.75 (95% confidence interval, 0.60-0.81), 0.71 (0.66-0.84), and 0.80 (0.71-0.88), respectively. Under the cutoff value of 3.6 mEq/L, hypokalemia had a sensitivity of 75% and specificity of 54% in predicting mortality."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"APACHE",
"Acute Disease",
"Adult",
"Female",
"Hospitals, University",
"Humans",
"Hypokalemia",
"Hypothermia",
"Male",
"Paraquat",
"Poisoning",
"Prognosis",
"Proportional Hazards Models",
"Retrospective Studies",
"Risk Factors",
"Survival Analysis"
]
} | The identified risk factors may allow better identification of those at greater mortality risk. Future development of a tailored clinical scoring system incorporating the identified risk factors for acute PQ poisoning may be of great help. | yes | [
{
"from": "human",
"value": "Question: Are hypokalemia and hypothermia associated with 30-day mortality in patients with acute paraquat poisoning?\nContext: {'contexts': ['Clinical predictors associated with acute paraquat (PQ) poisoning have not been systematically studied.', 'To identify independent predictors of death in patients with acute PQ poisoning.', 'This is a retrospective study executed in the emergency department of a university hospital. One hundred three consecutive patients poisoned with PQ between January 1999 and December 2004 were enrolled. Urine PQ concentration, electrolyte and renal function, detailed history, and Acute Physiology and Chronic Health Evaluation II were extracted from medical records. The outcome measure was 30-day mortality. Multivariate analysis was done by Cox-proportional hazard regression model. Receiver operating characteristics area under the curve was calculated for selected predictors.', 'The crude 30-day mortality was 67.9% (70 of 103). Independent predictors of death were acute renal failure (hazard ratio, 3.53; 95% confidence interval, 1.97-6.32), hypokalemia (2.07, 1.21-3.51), hypothermia (2.91, 1.67-5.07), suicide (2.11, 1.04-4.29), and self-reported ingested dose (2.06, 1.38-3.06). The receiver operating characteristics area under the curve of serum potassium concentrations, maximal urine PQ concentrations, and Acute Physiology and Chronic Health Evaluation II scores were 0.75 (95% confidence interval, 0.60-0.81), 0.71 (0.66-0.84), and 0.80 (0.71-0.88), respectively. Under the cutoff value of 3.6 mEq/L, hypokalemia had a sensitivity of 75% and specificity of 54% in predicting mortality.'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'METHODS', 'RESULTS'], 'meshes': ['APACHE', 'Acute Disease', 'Adult', 'Female', 'Hospitals, University', 'Humans', 'Hypokalemia', 'Hypothermia', 'Male', 'Paraquat', 'Poisoning', 'Prognosis', 'Proportional Hazards Models', 'Retrospective Studies', 'Risk Factors', 'Survival Analysis']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,552,570 | Does partial adherence to antihypertensive therapy fail to achieve full cardiovascular benefits in hypertensive rats? | {
"contexts": [
"Partial adherence to antihypertensive therapy remains a public health challenge and may be associated with increased cardiovascular risk. We quantitatively evaluated cardiovascular risk inherent in partial therapy adherence in spontaneously hypertensive rats with accelerated hypertension.",
"Adult spontaneously hypertensive rats were divided into 5 groups; Group 1 (controls) did not receive any treatment, whereas all other rats (Groups 2-5) were given nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester (L-NAME) to exacerbate hypertension. Group 2 (untreated/nonadherers) was given L-NAME but not antihypertensive medication; Group 3 (Perfect Adherers) was treated daily with candesartan (10 mg/kg); Group 4 was given candesartan 3 times a week, whereas Group 5 received candesartan only during the last 6 days of the 3-week experiment (Partial Adherers). At the end, indices of systemic and regional (kidneys, brain, and heart) hemodynamics, and indices of left ventricular function were determined.",
"Treatment with L-NAME aggravated hypertension, adversely affected target organ blood flows and resistances, and grossly impaired ventricular function. Perfect adherence with candesartan completely reversed the adverse cardiovascular effects of L-NAME intervention. In partial adherers (Groups 4 and 5), arterial pressure decreased and reached control values. However, target organ hemodynamics and heart function showed only slight improvements, if any."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Antihypertensive Agents",
"Benzimidazoles",
"Body Weight",
"Disease Models, Animal",
"Drug Administration Schedule",
"Hemodynamics",
"Hypertension",
"Male",
"Organ Size",
"Patient Compliance",
"Rats",
"Rats, Inbred SHR",
"Tetrazoles",
"Treatment Outcome",
"Ventricular Function, Left"
]
} | The results demonstrate that partial adherence to therapy reduces arterial pressure, but may not prevent target organ damage. If replicated in humans, these results may have important clinical implications in hypertensive patients. | yes | [
{
"from": "human",
"value": "Question: Does partial adherence to antihypertensive therapy fail to achieve full cardiovascular benefits in hypertensive rats?\nContext: {'contexts': ['Partial adherence to antihypertensive therapy remains a public health challenge and may be associated with increased cardiovascular risk. We quantitatively evaluated cardiovascular risk inherent in partial therapy adherence in spontaneously hypertensive rats with accelerated hypertension.', 'Adult spontaneously hypertensive rats were divided into 5 groups; Group 1 (controls) did not receive any treatment, whereas all other rats (Groups 2-5) were given nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester (L-NAME) to exacerbate hypertension. Group 2 (untreated/nonadherers) was given L-NAME but not antihypertensive medication; Group 3 (Perfect Adherers) was treated daily with candesartan (10 mg/kg); Group 4 was given candesartan 3 times a week, whereas Group 5 received candesartan only during the last 6 days of the 3-week experiment (Partial Adherers). At the end, indices of systemic and regional (kidneys, brain, and heart) hemodynamics, and indices of left ventricular function were determined.', 'Treatment with L-NAME aggravated hypertension, adversely affected target organ blood flows and resistances, and grossly impaired ventricular function. Perfect adherence with candesartan completely reversed the adverse cardiovascular effects of L-NAME intervention. In partial adherers (Groups 4 and 5), arterial pressure decreased and reached control values. However, target organ hemodynamics and heart function showed only slight improvements, if any.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Animals', 'Antihypertensive Agents', 'Benzimidazoles', 'Body Weight', 'Disease Models, Animal', 'Drug Administration Schedule', 'Hemodynamics', 'Hypertension', 'Male', 'Organ Size', 'Patient Compliance', 'Rats', 'Rats, Inbred SHR', 'Tetrazoles', 'Treatment Outcome', 'Ventricular Function, Left']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,571,985 | Does percutaneous coronary intervention for acute MI prevent in-hospital development of cardiogenic shock compared to fibrinolysis? | {
"contexts": [
"It has been speculated that invasive revascularization prevents development of cardiogenic shock. Data from randomised trials comparing angioplasty with fibrinolysis on the development of cardiogenic shock are lacking.",
"To elucidate the effect of angioplasty on in-hospital development of cardiogenic shock compared to fibrinolysis. To evaluate whether mortality in patients who develop cardiogenic shock after treatment is dependent on revascularization strategy.",
"DANAMI-2 randomly assigned 1572 STEMI patients to fibrinolysis (782 patients) or angioplasty (790 patients). Data on patients with in-hospital development of cardiogenic shock after randomisation were included. Of the 103 patients (6.6%) patients developing cardiogenic shock 57% were randomised to angioplasty with an unadjusted odds ratio of 1.39 (0.92-2.11, p=0.14). During the three year follow-up 58% of the total mortality was due to cardiogenic shock, and treatment strategy did not influence the risk associated with shock (hazard ratio of 1.05 (0.67-1.64) for angioplasty vs. fibrinolysis)."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Aged, 80 and over",
"Angioplasty, Balloon, Coronary",
"Chi-Square Distribution",
"Denmark",
"Female",
"Hospital Mortality",
"Humans",
"Incidence",
"Male",
"Middle Aged",
"Myocardial Infarction",
"Proportional Hazards Models",
"Registries",
"Shock, Cardiogenic",
"Thrombolytic Therapy",
"Treatment Outcome"
]
} | Angioplasty does not prevent the in-hospital development of cardiogenic shock complicating acute MI compared to fibrinolysis. Cardiogenic shock is still the leading cause of death in patients hospitalised for acute MI. There was no difference in mortality, with regards to treatment strategy in patients developing cardiogenic shock after the initial treatment. | no | [
{
"from": "human",
"value": "Question: Does percutaneous coronary intervention for acute MI prevent in-hospital development of cardiogenic shock compared to fibrinolysis?\nContext: {'contexts': ['It has been speculated that invasive revascularization prevents development of cardiogenic shock. Data from randomised trials comparing angioplasty with fibrinolysis on the development of cardiogenic shock are lacking.', 'To elucidate the effect of angioplasty on in-hospital development of cardiogenic shock compared to fibrinolysis. To evaluate whether mortality in patients who develop cardiogenic shock after treatment is dependent on revascularization strategy.', 'DANAMI-2 randomly assigned 1572 STEMI patients to fibrinolysis (782 patients) or angioplasty (790 patients). Data on patients with in-hospital development of cardiogenic shock after randomisation were included. Of the 103 patients (6.6%) patients developing cardiogenic shock 57% were randomised to angioplasty with an unadjusted odds ratio of 1.39 (0.92-2.11, p=0.14). During the three year follow-up 58% of the total mortality was due to cardiogenic shock, and treatment strategy did not influence the risk associated with shock (hazard ratio of 1.05 (0.67-1.64) for angioplasty vs. fibrinolysis).'], 'labels': ['BACKGROUND', 'OBJECTIVE', 'RESULTS'], 'meshes': ['Adult', 'Aged', 'Aged, 80 and over', 'Angioplasty, Balloon, Coronary', 'Chi-Square Distribution', 'Denmark', 'Female', 'Hospital Mortality', 'Humans', 'Incidence', 'Male', 'Middle Aged', 'Myocardial Infarction', 'Proportional Hazards Models', 'Registries', 'Shock, Cardiogenic', 'Thrombolytic Therapy', 'Treatment Outcome']}"
},
{
"from": "gpt",
"value": "Answer: no"
}
]
|
18,571,988 | Are demographic , clinical , and pain characteristics associated with average pain severity groups in a sample of oncology outpatients? | {
"contexts": [
"Cut-points (CP) for pain severity are useful because they may help clinicians to identify patients with clinically significant pain. However, a need exists to evaluate whether different pain severity groups differ on selected demographic, clinical, and pain characteristics, as well as on factors that may be amenable to psychoeducational interventions such as self-efficacy for pain management, coping strategies, and barriers to pain management. In this cross-sectional study of 210 oncology outpatients with pain, an optimal CP of 4 was found using ratings of average pain intensity. The variables that provided a unique contribution to the prediction of membership in the >4 CP group were gender, presence of breakthrough pain, comorbidities, barriers to pain management, and total self-efficacy for pain management. In addition, patients in the >4 CP group reported lower scores on physical, role, cognitive, and global health function."
],
"labels": [
"UNLABELLED"
],
"meshes": [
"Aged",
"Cross-Sectional Studies",
"Female",
"Humans",
"Male",
"Middle Aged",
"Neoplasms",
"Norway",
"Outpatients",
"Pain",
"Pain Measurement",
"Reference Values",
"Severity of Illness Index",
"Surveys and Questionnaires"
]
} | An average pain CP of >4 could be used to screen oncology outpatients with clinically significant pain. Clinicians must consider a number of demographic, clinical, and pain characteristics as part of their pain assessment procedures. The effectiveness of psychoeducational interventions aimed at barriers and patients self-efficacy for pain management need to be tested. | yes | [
{
"from": "human",
"value": "Question: Are demographic , clinical , and pain characteristics associated with average pain severity groups in a sample of oncology outpatients?\nContext: {'contexts': ['Cut-points (CP) for pain severity are useful because they may help clinicians to identify patients with clinically significant pain. However, a need exists to evaluate whether different pain severity groups differ on selected demographic, clinical, and pain characteristics, as well as on factors that may be amenable to psychoeducational interventions such as self-efficacy for pain management, coping strategies, and barriers to pain management. In this cross-sectional study of 210 oncology outpatients with pain, an optimal CP of 4 was found using ratings of average pain intensity. The variables that provided a unique contribution to the prediction of membership in the >4 CP group were gender, presence of breakthrough pain, comorbidities, barriers to pain management, and total self-efficacy for pain management. In addition, patients in the >4 CP group reported lower scores on physical, role, cognitive, and global health function.'], 'labels': ['UNLABELLED'], 'meshes': ['Aged', 'Cross-Sectional Studies', 'Female', 'Humans', 'Male', 'Middle Aged', 'Neoplasms', 'Norway', 'Outpatients', 'Pain', 'Pain Measurement', 'Reference Values', 'Severity of Illness Index', 'Surveys and Questionnaires']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
18,559,352 | Does neostigmine but not sugammadex impair upper airway dilator muscle activity and breathing? | {
"contexts": [
"Cholinesterase inhibitor-based reversal agents, given in the absence of neuromuscular block, evoke a partial upper airway obstruction by decreasing skeletal upper airway muscle function. Sugammadex reverses neuromuscular block by encapsulating rocuronium. However, its effects on upper airway integrity and breathing are unknown.",
"Fifty-one adult male rats were anaesthetized with isoflurane, tracheostomized, and a femoral artery and vein were cannulated. First, we compared the efficacy of sugammadex 15 mg kg(-1) and neostigmine 0.06 mg kg(-1) to reverse respiratory effects of rocuronium-induced partial paralysis [train-of-four ratio (T4/T1)=0.5]. Subsequently, we compared the safety of sugammadex and neostigmine given after recovery of the T4/T1 to 1, by measuring phasic genioglossus activity and breathing.",
"During partial paralysis (T4/T1=0.5), time to recovery of minute volume to baseline values was 10.9 (2), 75.8 (18), and 153 (54) s with sugammadex, neostigmine, and placebo, respectively (sugammadex was significantly faster than neostigmine and placebo, P<0.05). Recovery of T4/T1 was also faster for sugammadex than neostigmine and placebo. Neostigmine administration after complete recovery of T4/T1 decreased upper airway dilator muscle activity to 64 (30)% of baseline and decreased tidal volume (P<0.05 for both variables), whereas sugammadex had no effect on either variable."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Androstanols",
"Anesthesia Recovery Period",
"Anesthetics, Inhalation",
"Animals",
"Cholinesterase Inhibitors",
"Electromyography",
"Isoflurane",
"Male",
"Neostigmine",
"Neuromuscular Blockade",
"Neuromuscular Nondepolarizing Agents",
"Rats",
"Rats, Sprague-Dawley",
"Respiration",
"Respiratory Muscles",
"Rocuronium",
"Sugammadex",
"gamma-Cyclodextrins"
]
} | In contrast to neostigmine, which significantly impairs upper airway dilator muscle activity when given after recovery from neuromuscular block, a reversal dose of sugammadex given under the same conditions does not affect genioglossus muscle activity and normal breathing. Human studies will be required to evaluate the clinical relevance of our findings. | yes | [
{
"from": "human",
"value": "Question: Does neostigmine but not sugammadex impair upper airway dilator muscle activity and breathing?\nContext: {'contexts': ['Cholinesterase inhibitor-based reversal agents, given in the absence of neuromuscular block, evoke a partial upper airway obstruction by decreasing skeletal upper airway muscle function. Sugammadex reverses neuromuscular block by encapsulating rocuronium. However, its effects on upper airway integrity and breathing are unknown.', 'Fifty-one adult male rats were anaesthetized with isoflurane, tracheostomized, and a femoral artery and vein were cannulated. First, we compared the efficacy of sugammadex 15 mg kg(-1) and neostigmine 0.06 mg kg(-1) to reverse respiratory effects of rocuronium-induced partial paralysis [train-of-four ratio (T4/T1)=0.5]. Subsequently, we compared the safety of sugammadex and neostigmine given after recovery of the T4/T1 to 1, by measuring phasic genioglossus activity and breathing.', 'During partial paralysis (T4/T1=0.5), time to recovery of minute volume to baseline values was 10.9 (2), 75.8 (18), and 153 (54) s with sugammadex, neostigmine, and placebo, respectively (sugammadex was significantly faster than neostigmine and placebo, P<0.05). Recovery of T4/T1 was also faster for sugammadex than neostigmine and placebo. Neostigmine administration after complete recovery of T4/T1 decreased upper airway dilator muscle activity to 64 (30)% of baseline and decreased tidal volume (P<0.05 for both variables), whereas sugammadex had no effect on either variable.'], 'labels': ['BACKGROUND', 'METHODS', 'RESULTS'], 'meshes': ['Androstanols', 'Anesthesia Recovery Period', 'Anesthetics, Inhalation', 'Animals', 'Cholinesterase Inhibitors', 'Electromyography', 'Isoflurane', 'Male', 'Neostigmine', 'Neuromuscular Blockade', 'Neuromuscular Nondepolarizing Agents', 'Rats', 'Rats, Sprague-Dawley', 'Respiration', 'Respiratory Muscles', 'Rocuronium', 'Sugammadex', 'gamma-Cyclodextrins']}"
},
{
"from": "gpt",
"value": "Answer: yes"
}
]
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.