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Single- and multiple-dose pharmacokinetics and tolerability of limaprost in healthy Chinese subjects.
Limaprost, a prostaglandin E1 analogue, is used to treat various symptoms in patients with ischemic diseases. The present study was designed to determine the pharmacokinetics and tolerability of single and multiple oral doses of limaprost 5 μg tablets in healthy Chinese subjects. Single and multiple doses of 5-μg limaprost were orally administered to 12 healthy Chinese subjects. There was a 2-week washout period between single and multiple dosing. Blood samples were collected at various times. Indomethacin and aspirin were added to the blood samples to inhibit the endogenous release of prostaglandins during the sample processing. Plasma limaprost was measured by a two-dimensional liquid chromatography-tandem mass spectrometry method. After single dosing, limaprost was rapidly absorbed (time to reach maximum plasma concentration [t max] = 22.50 min) and eliminated (elimination half-life [t ½] = 21.70 min), with the maximum plasma concentration (C max) being 2.56 pg/mL and area under the concentration-time curve (AUC) from time 0 to the last quantifiable time point (AUC0-t) being 70.68 pg·min/mL. There were significant inter-individual variations in the AUCs for both single- and multiple-dose regimens. The values of C max, AUC, t ½ and t max were not statistically different between single and multiple dosing. The accumulation factor R was 0.609 ± 0.432 (R < 1), indicating that there was no accumulation after multiple dosing. There were no statistically significant differences in pharmacokinetic parameters for both single and multiple dosing between female and male subjects. The drug was well tolerated, with no severe adverse events being observed. Limaprost is rapidly absorbed after oral administration and is rapidly eliminated, with no accumulation after multiple dosing. The drug is well tolerated and no serious adverse events occurred. | {
"pile_set_name": "PubMed Abstracts"
} |
Early emergence of opportunistic infections after starting direct-acting antiviral drugs in HIV/HCV-coinfected patients.
Varicella-zoster virus and hepatitis B virus reactivations have been reported after starting interferon-free direct-acting antiviral agent (DAA) combinations. HIV/HCV-coinfected patients could be a high-risk group for the reactivation of latent infections. Because of these, we report the occurrence of severe infections after starting DAA regimens in HIV/HCV-coinfected patients. Individuals included in the HEPAVIR-DAA (NCT02057003) cohort were selected if they had received all-oral DAA combinations. A retrospective review of clinical events registered between the start of DAAs and 12 months after SVR12 was carried out. Overall, 38 (4.5%) of 848 patients presented infections. The incidence (95% confidence interval) of infections was 4.6 (3.3-6.3) cases per 100 person-years. The median (Q1-Q3) time to the infection since baseline was 23 (7.3-33) weeks. Five (13%) of the patients with infections died; four of them had cirrhosis. The frequency of previous AIDS was 21 (54%) for patients with infections and 324 (40%) for those without infections (P = 0.084). The median (Q1-Q3) nadir CD4 cell count of individuals with and without infections was 75 (53-178) and 144 (67-255) cells/μL, respectively (P = 0.047). Immunodepression-associated infections were observed in 9 (1.1%) patients. All of them had suppressed HIV replication with antiretroviral therapy. In conclusion, severe infections are relatively common among HIV/HCV-coinfected patients receiving all-oral DAA combinations. Some unusual reactivations of latent infections in patients with suppressed HIV replication seem to be temporally linked with DAA use. | {
"pile_set_name": "PubMed Abstracts"
} |
Orthogonal Regulatory Circuits for Escherichia coli Based on the γ-Butyrolactone System of Streptomyces coelicolor.
Chemically inducible transcription factors are widely used to control gene expression of synthetic devices. The bacterial quorum sensing system is a popular tool to achieve such control. However, different quorum sensing systems have been found to cross-talk, both between themselves and with the hosts of these devices, and they are leaky by nature. Here we evaluate the potential use of the γ-butyrolactone system from Streptomyces coelicolor A3(2) M145 as a complementary regulatory circuit. First, two additional genes responsible for the biosynthesis of γ-butyrolactones were identified in S. coelicolor M145 and then expressed in E. coli BL21 under various experimental conditions. Second, the γ-butyrolactone receptor ScbR was optimized for expression in E. coli BL21. Finally, signal and promoter crosstalk between the γ-butyrolactone system from S. coelicolor and quorum sensing systems from Vibrio fischeri and Pseudomonas aeruginosa was evaluated. The results show that the γ-butyrolactone system does not crosstalk with the quorum sensing systems and can be used to generate orthogonal synthetic circuits. | {
"pile_set_name": "PubMed Abstracts"
} |
Inhibitory control is not lateralized in Parkinson's patients.
Parkinson's disease (PD) is often characterized by asymmetrical symptoms, which are more prominent on the side of the body contralateral to the most extensively affected brain hemisphere. Therefore, lateralized PD presents an opportunity to examine the effects of asymmetric subcortical dopamine deficiencies on cognitive functioning. As it has been hypothesized that inhibitory control relies upon a right-lateralized pathway, we tested whether left-dominant PD (LPD) patients suffered from a more severe deficit in this key executive function than right-dominant PD patients (RPD). To this end, via a countermanding task, we assessed both proactive and reactive inhibition in 20 LPD and 20 RPD patients, and in 20 age-matched healthy subjects. As expected, we found that PD patients were significantly more impaired in both forms of inhibitory control than healthy subjects. However, there were no differences either in reactive or proactive inhibition between LPD and RPD patients. All in all, these data support the idea that brain regions affected by PD play a fundamental role in subserving inhibitory function, but do not sustain the hypothesis according to which this executive function is predominantly or solely computed by the brain regions of the right hemisphere. | {
"pile_set_name": "PubMed Abstracts"
} |
Determination of Labeled Fatty Acids Content in Milk Products, Infant Formula, and Adult/Pediatric Nutritional Formula by Capillary Gas Chromatography: Collaborative Study, Final Action 2012.13.
A collaborative study was conducted on AOAC First Action Method 2012.13 "Determination of Labeled Fatty Acids Content in Milk Products and Infant Formula by Capillary Gas Chromatography," which is based on an initial International Organization for Standardization (ISO)-International Dairy Federation (IDF) New Work Item that has been moved forward to ISO 16958:2015|IDF 231:2015 in November 2015. It was decided to merge the two activities after the agreement signed between ISO and AOAC in June 2012 to develop common standards and to avoid duplicate work. The collaborative study was performed after having provided highly satisfactory single-laboratory validation results [Golay, P.A., & Dong, Y. (2015) J. AOAC Int. 98, 1679-1696] that exceeded the performance criteria defined in AOAC Standard Method Performance Requirement (SMPR(®)) 2012.011 (September 29, 2012) on 12 products selected by the AOAC Stakeholder Panel on Infant Formula (SPIFAN). After a qualification period of 1 month, 18 laboratories participated in the fatty acids analysis of 12 different samples in duplicate. Six samples were selected to meet AOAC SPIFAN requirements (i.e., infant formula and adult nutritionals in powder and liquid formats), and the other Six samples were selected to meet ISO-IDF requirements (i.e., dairy products such as milk powder, liquid milk, cream, butter, infant formula with milk, and cheese). The fatty acids were analyzed directly in all samples without preliminary fat extraction, except in one sample (cheese). Powdered samples were analyzed after dissolution (i.e., reconstitution) in water, whereas liquid samples (or extracted fat) were analyzed directly. After addition of the internal standards solution [C11:0 fatty acid methyl ester (FAME) and C13:0 triacylglycerols (TAG)] to the samples, fatty acids attached to lipids were transformed into FAMEs by direct transesterification using methanolic sodium methoxide. FAMEs were separated using highly polar capillary GLC and were identified by comparison with the retention times of pure analytical standards. Quantification of fatty acids was done relative to C11:0 FAME as internal standard and to instrument response factors (determined separately using calibration standards mixture). The performance of the method (i.e., transesterification) was monitored in all samples using the second internal standard, C13:0 TAG. RSDR values were summarized separately for labeled fatty acids in SPIFAN materials and ISO-IDF materials due to different expression of results. This method was applied to representative dairy, infant formula, and adult/pediatric nutritional products and demonstrated global acceptable reproducibility precision for all fatty acids analyzed (i.e., 46 individuals and/or groups) for these categories of products. | {
"pile_set_name": "PubMed Abstracts"
} |
Intramedullary tuberculomas of the spinal cord: case report and review.
Intramedullary spinal tuberculomas are a rare cause of spinal cord compression. We report a recent case and review 17 cases described in the literature since 1960. Intramedullary spinal tuberculomas occurred in relatively young patients (mean age, 28.6 years) and more frequently in women (63% of cases) than in men. The commonest symptoms were those of subacute spinal cord compression (mean duration, 2.3 months) with progressive lower-limb weakness (94%), paresthesia, and bowel and bladder dysfunction. The major physical finding was paraplegia, either spastic (61%) or flaccid (33%). The majority of patients (55%) had a thoracic sensory level. Extraspinal tuberculous disease, predominantly pulmonary, occurred in 69% of reported cases. Myelography efficiently localized the lesion. The diagnosis was made surgically in 16 patients (89%) and clinically in two (11%). Eleven (65%) of 17 patients improved. Four deaths occurred, three in the perioperative period. Though rare, intramedullary spinal cord tuberculoma should be considered in the differential diagnosis of spinal cord compression, particularly when clinical disease compatible with tuberculosis is present. | {
"pile_set_name": "PubMed Abstracts"
} |
T lymphocyte subpopulations in leprosy patients and their relation with circulating immune complexes.
The possible relationship between circulating immune complexes (CIC) and peripheral T lymphocyte populations was studied in thirteen active multibacillary leprosy (10 lepromatous--LL--and 3 borderline lepromatous--BL--) and 19 matched controls. Theophylline-resistant T cells (The-R, a lymphocyte subpopulation displaying helper activity on B cells) and total T cells were assessed by means of the E rosette technique, with and without previous theophylline incubation, 1h 37 degrees C, respectively. CIC were quantified by 125I-C1q binding test. Although leprosy patients showed a statistical non significant light depression in total T cells the remarkable variability in circulating levels of The-R T cells enabled us to separate them into two well delineated groups (in relation to this variable p less than 0.001) with no difference in age, sex and bacteriologic state: a) leprosy patients with The-R T cells proportionally conserved (6LL and 2BL); b) leprosy patients with The-R T cells proportionally depressed (4LL and 1BL). Patients belonging to the latter group showed the highest statistically significant levels of CIC. Even though we do not discard an unknown factor being responsible for our findings, we believe that this inverse relationship between elevated CIC and depressed The-R circulating T cells might be representing a lower helper activity on antibody synthesis intending to reduce its excessive production. | {
"pile_set_name": "PubMed Abstracts"
} |
Biotransformation and pharmacokinetics of 4-(3,4-dihydroxybenzoyloxymethyl)phenyl-O-beta-D-glucopyranoside, an antioxidant isolated from Origanum vulgare.
4-(3,4-Dihydroxybenzoyloxymethyl)phenyl- O-beta-D-glucopyranoside (OV-16) is a polyphenolic glycoside isolated from oregano (Origanum vulgare L.), which is a popular Chinese herb and a common spice in Western diet. To understand the biotransformation and pharmacokinetics of OV-16, rats were orally administered OV-16 and oregano decoction. Blood samples were withdrawn at specific time points. The presence of OV-16 and its metabolites protocatechuic acid (PCA) and p-hydroxybenzyl alcohol (HBA) in serum were determined by HPLC method, whereas their conjugated metabolites were assayed indirectly through hydrolysis with beta-glucuronidase and sulfatase. Our results showed that when OV-16 was orally administered, free forms of OV-16, PCA, and HBA were not present in blood and the major metabolites were the glucuronides/sulfates of PCA and HBA sulfate. The serum metabolites of OV-16 exhibited free radical scavenging activity. When oregano decoction was given, the glucuronides and sulfates of PCA were the major metabolites in blood. | {
"pile_set_name": "PubMed Abstracts"
} |
The DNA restriction endonuclease of Escherichia coli B. I. Studies of the DNA translocation and the ATPase activities.
Electron microscopic examination of DNA intermediates formed by the restriction endonuclease of Escherichia coli B revealed supercoiled loops that are presumably formed during an ATP-dependent DNA translocation process in which the enzyme remains bound to the recognition site while tracking along the DNA helix to a cleavage site. The rate of DNA translocation during this process is at least 5000 base pairs/min at 37 degrees C. Even after all cleavages have been completed, complexes are seen that contain terminal loops or loop plus tail structures. During this later phase of the reaction, ATP is hydrolyzed at a rate which is dependent upon the size of the largest possible loop (or loop plus tail); this ATP hydrolysis can be terminated by one double-strand cleavage within the loop region between the recognition site and the terminus. To explain these results, it is hypothesized that after cleavage the enzyme cycles between a tracking (and possibly back-tracking) mode which is fueled by ATP hydrolysis and a relatively long static period in which ATP hydrolysis does not occur. While tracking, the enzyme would be bound both to the recognition site and to a distal site but, while static, the enzyme would be bound only at the recognition site of nonlooped molecules. This post-nuclease phase of the reaction is hypothesized to reflect a reaction whereby the enzyme initially scans DNA molecules before making a strand cleavage. | {
"pile_set_name": "PubMed Abstracts"
} |
Parasitic arthropods of sympatric meadow voles and white-footed mice at Fort Detrick, Maryland.
Twelve species of parasitic arthropods (one sucking louse, two fleas, one tick, and eight mites) were recovered from 51 meadow voles, Microtus pennsylvanicus (Ord); whereas nine species (one sucking louse, one bot, three fleas, one tick, and three mites) were collected from 48 white-footed mice, Peromyscus leucopus (Rafinesque), live-trapped on the grounds of Fort Detrick, Frederick County, MD., during 1990 and 1991. The most commonly collected arthropods from M. pennsylvanicus were the fur mite, Listrophorus mexicanus Fain (approximately 2,720 specimens); the tropical rat mite, Ornithonyssus bacoti (Hirst) (987); the laelapid mites, Laelaps kochi Oudemans (733) and Androlaelaps fahrenholzi (Berlese (322); the sucking louse, Hoplopleura acanthopus (Burmeister) (121); the tick, Dermacentor variabilis (Say) (47); and the chigger mite, Neotrombicula whartoni (Ewing) (45). Arthropod densities were lower on P. leucopus, from which the most frequently recorded species were the sucking louse, Hoplopleura hesperomydis (Osborn) (98 specimens); the fleas, Epitedia wenmanni (Rothschild) (85) and Orchopeas leucopus (Baker) (61); and the mite, A. fahrenholzi (83). Although six species of arthropods parasitized both species of rodents, only two of these, A. fahrenholzi and D. variabilis, were relatively common on both hosts. Therefore, although the habitats of both host species partially overlap, their associated parasitic arthropods remain principally host specific. The potential significance of these findings with respect to vector-borne disease transmission is discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
The antidepressants maprotiline and fluoxetine induce Type II autophagic cell death in drug-resistant Burkitt's lymphoma.
Resistance to chemotherapy is a major obstacle for the success of cancer therapy and is most commonly attributed to the inability of cancer cells to die by apoptosis, the archetypal programed cell death (PCD) response. The development of anticancer drugs that can overcome this resistance to apoptosis and induce other forms of cell death is therefore paramount for efficient cancer therapy. We report that the antidepressants maprotiline and fluoxetine induce autophagic PCD in the chemoresistant Burkitt's lymphoma (BL) cell line DG-75, which does not involve caspases, DNA fragmentation or PARP cleavage, but is associated with the development of cytoplasmic vacuoles, all consistent with an autophagic mode of PCD. Autophagic PCD was confirmed by transmission electron microscopy, upregulation of Beclin-I and the extent of PCD being reduced by the autophagic inhibitor 3-MA. In contrast, these compounds induced apoptotic PCD in the biopsy-like chemosensitive BL MUTU-I cell line. We provide evidence that the chemoresistant DG-75 cells do not express the proapoptotic Bcl-2 proteins Bax and Bak, show diminished levels of stored intracellular calcium and display shortened rod-like mitochondria, all of which are known to be associated with a defective "apoptotic" response in cancer cells. PCD in the two cell lines has different Ca(2+) responses to maprotiline and fluoxetine, which may also account for their differential PCD responses. Our study, therefore, supports a new mechanistic role for maprotiline and fluoxetine as novel proautophagic agents in the treatment of resistant BL, and thus an alternative therapeutic application for these compounds. | {
"pile_set_name": "PubMed Abstracts"
} |
Daptomycin for the treatment of infective endocarditis: results from a European registry.
Infective endocarditis (IE) is a complex infection associated with high mortality. Daptomycin, a cyclic lipopeptide antibiotic highly active against Gram-positive bacteria, has recently been incorporated into IE treatment guidelines. This retrospective analysis provides insights into the use of daptomycin in IE in the European Cubicin(®) Outcomes Registry Experience (EU-CORE(SM)) between 2006 and 2010. Three hundred and seventy-eight (10%) of 3621 enrolled patients received daptomycin for treatment of IE. Two hundred and fifty-nine (69%) had left-sided IE (LIE) and 182 patients (48%) underwent concomitant surgery. Staphylococcus aureus was the most frequently identified pathogen (n=92; methicillin susceptible, n=50) and daptomycin was used empirically in 134 patients. Among cases of second-line therapy (n=312), the most common reason for switching to daptomycin was failure of the previous regimen (including glycopeptides and penicillins). Daptomycin was administered at 6 mg/kg in 224 patients and at ≥ 8 mg/kg in 72 patients. Clinical success rates were 80% overall, 91% for right-sided IE (RIE) and 76% for LIE, with similar rates seen for infections caused by methicillin-susceptible S. aureus (84%) and methicillin-resistant S. aureus (81%). The clinical success rate in patients treated with ≥ 8 mg/kg daptomycin was 90% [n=72 (RIE, 91%; LIE, 89%)]. No new safety signals were observed. In patients with IE registered in EU-CORE, daptomycin was most frequently used as second-line treatment after treatment failure. The majority of patients had LIE and most commonly received daptomycin for the treatment of staphylococcal infections. Clinical success was high in this difficult-to-treat population. The role of doses ≥ 8 mg/kg per day in the empirical treatment of IE deserves further investigation. | {
"pile_set_name": "PubMed Abstracts"
} |
Nutritionally induced relationships between insulin levels during the weaning-to-ovulation interval and reproductive characteristics in multiparous sows: I. Luteinizing hormone, follicle development, oestrus and ovulation.
To get more insight in how insulin secretion patterns and corresponding insulin-like growth factor-1 (IGF-1) levels are related to luteinizing hormone (LH) secretion, follicle development and ovulation, 32 multiparous sows were fed either a dextrose plus lactose-containing diet at 4 h intervals (DL; each 150 g/day) or an isocaloric control diet at 12 h intervals (CTRL; containing soybean oil) during the weaning-to-ovulation interval (WOI). Insulin parameters (basal, peak levels and mean insulin) and IGF-1 levels during the WOI were similar for both treatments, but the insulin secretion pattern differed (related with feeding frequency and meal sizes). Oestrus and ovulation characteristics were not influenced by treatment. The LH surge was higher in CTRL compared with DL sows (3.73 vs 3.00 ng/ml; p = 0.03). Average diameter (6.5 vs 6.1 mm; p = 0.08) and uniformity (CV: 11 vs 15%, p = 0.02) of follicles ≥3 mm at day 4 after weaning was higher in CTRL compared with DL sows. Basal insulin levels were positively related with follicle diameter at ovulation (β = 0.05 mm/(μU/ml); p = 0.04) and negatively related with LH surge level (β = -0.07 (ng/ml)/(μU/ml); p = 0.01). Insulin area under the curve (AUC) (β = 0.037 (ng/ml)/1000 μU; p = 0.02) and IGF-1 levels (β = 0.002 (ng/ml)/(ng/ml); p < 0.01) were positively related to basal LH level around the LH surge. From these data, we conclude that insulin and IGF-1 levels during the WOI are related to LH secretion and follicle development. Not only the absolute level of insulin seems important, but also the pattern within a day in which insulin is secreted seems to affect LH secretion and development of pre-ovulatory follicles. | {
"pile_set_name": "PubMed Abstracts"
} |
Prevalence of acute kidney injury in intensive care units: the "COrte de prevalencia de disFunción RenAl y DEpuración en críticos" point-prevalence multicenter study.
This study aimed to measure the point prevalence of kidney dysfunction (KD) in the intensive care setting. A point-prevalence, single-day, prospective study was conducted. Of 919 patients present in 42 Intensive care units (ICUs) for 2 specific days (September 2009 and March 2010), 832 cases were included. Mild KD was defined as a measured creatinine clearance of 90 to 60 mL min(-1) 1.73 m(-2), and severe KD was defined as a creatinine clearance less than 60 mL min(-1) 1.73 m(-2). Prevalence of mild KD was 15.9/100 patients/d (13.5-18.5), and severe KD was 42.4/100 patients/d (39.1-45.8). We considered as having a low probability of experiencing KD those patients without chronic kidney disease, acute kidney injury network stage 0, and a serum creatinine less than 1.2 mg/dL, but among them (557 patients), 18.1% (15.2%-21.6%) had mild KD and 24.2% (20.9%-28%) had severe KD. ICU mortality was 10.6% (7.81%-14.4%) for patients without dysfunction, 16.6% (11.2%-24%) for patients with mild KD, and 29.7% (25.2%-34.7%; P<.001) for patients with severe KD, with a relative risk for severe KD vs no KD of 2.54 (1.90-3.40). In 54.3% patients, at least 1 renal insult was reported. One nephrotoxic drug was administered to 34.4% and 2 or more to 14.9% patients, with a lower frequency among those with chronic kidney disease (30.6% vs 50.8%; P<.05). Each day of study, more that half of the patients admitted to the ICU showed some derangement in kidney function. More than 25% of patients not fulfilling the KD criteria by serum creatinine or acute kidney injury network showed, in fact, a severe KD, and this finding was associated with higher mortality. More than 50% of the patients admitted to the ICU were subjected to at least 1 renal insult. | {
"pile_set_name": "PubMed Abstracts"
} |
The monthly rhythm of incidence and age at menarche: thirty five years of research. The circa-vacation-study expectancy rhythm of incidence and age at menarche.
The hypothesis that the vacation-study-expectancy scholar regime produces most of the monthly rhythm of the age at menarche (AaM) was tested. Studies on monthly menarche incidence (MI) refuted climatic factors as a main factor in this rhythm, and indicated that the main factor of this rhythm is the succession of expectancies of study (Stu-months) or vacation (Vac-months) months within a year. Thus the hypothesis of seasonal circa-annual rhythm should be modified to the circa-[vacation (fiesta)]-[study (non-fiesta)]-expectancies rhythm for the MI and age at menarche annual rhythms. In several countries Vac-months had higher MI than Stu-months. The high MI of Vac-months was followed by a large decrease when girls started their studies and a MI increase occurred as vacations approached. The hypothesis proposes that at the end of vacations and at the beginning of the study period the AaM should be lowest, and then the mean of AaM should increase because of the menarche delay of girls whose menarche was arrested by the initiation of school work. This pattern was found in four independent samples, from Chile, Colombia, USA and Brazil. The probability that this result be due to random fluctuation of means is extraordinarily low (P<10⁻⁸). I conclude that the influence of the expectancy of vacation and study periods on the monthly rhythm of the age at menarche is a real process that accounts for most of this rhythm. | {
"pile_set_name": "PubMed Abstracts"
} |
Open pore block of connexin26 and connexin32 hemichannels by neutral, acidic and basic glycoconjugates.
The mechanisms of molecular discrimination by connexin channels are of acute biological and medical importance. The availability of affinity or open-pore blocking reagents for reliable and specific study of the connexin permeability pathway, would make possible the rigorous cellular and physiological studies required to inform, in molecular terms, the underlying role of intercellular communication pathways in development and disease. Previous work utilized a series of glucosaccharides labeled with an uncharged fluorescent aminopyridine (PA-) group to establish steric constraints to permeability through connexin hemichannels. In that work, the smallest probe permeable through homomeric Cx26 and heteromeric Cx26-Cx32 channels was the PA-disaccharide, and the smallest probe permeable through homomeric Cx32 channels was the PA-trisaccharide. The larger impermeable probes did not block permeation of the smaller probes. Building on this work, a new set of glucosaccharide probes was developed in which the label was one of a homologous series of novel anthranilic acid derivatives (ABG) that carry negative or positive formal charge or remain neutral at physiological pH. When the PA-label of the smallest impermeant PA-derivatized oligosaccharides was replaced by ABG label, the resulting probes acted as reversible, high-affinity inhibitors of large molecule permeation through connexin pores in a size and connexin-specific manner. | {
"pile_set_name": "PubMed Abstracts"
} |
1,25-Dihydroxyvitamin D3-induced upregulation of the thyrotropin-releasing hormone receptor in clonal rat pituitary GH3 cells.
1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) is active in primary dispersed and clonal pituitary cells where it stimulates pituitary hormone production and agonist-induced hormone release. We have studied the effect of 1,25-(OH)2D3 on thyrotropin-releasing hormone (TRH) binding in clonal rat pituitary tumour (GH3) cells. Compared with vehicle-treated cells, 1,25-(OH)2D3 (10 nmol/l) increased specific [3H]MeTRH binding by 26% at 8 h, 38% at 16 h, 35% at 24 h and reached a maximum at 48 h (90%). In dose-response experiments, specific [3H]MeTRH binding increased with 1,25-(OH)2D3 concentration and reached a maximum at 10 nmol/l. Half-maximal binding occurred at 0.5 nmol 1,25-(OH)2D3/l. The vitamin D metabolite, 25-OH D3, increased [3H]MeTRH binding but was 1000-fold less potent than 1,25-(OH)2D3. In equilibrium binding assays, treatment with 10 nmol 1,25-(OH)2D3/l for 48 h increased the maximum binding from 67.4 +/- 8.8 fmol/mg protein in vehicle-treated cells to 96.7 +/- 12.4 fmol/mg protein in treated cells. There was no difference in apparent Kd (1.08 +/- 0.10 nmol/l for 1,25-(OH)2D3-treated and 0.97 +/- 0.11 nmol/l for vehicle-treated cells). Molecular investigations revealed that 10 nmol 1,25-(OH)2D3/l for 24 h caused an 8-fold increase in TRH receptor-specific mRNA. Actinomycin D (2 micrograms/ml, 6 h) abrogated the 1,25-(OH)2D3-induced increase in [3H]MeTRH binding. Cortisol also increased [3H]MeTRH binding but showed no additivity or synergism with 1,25-(OH)2D3. TRH-stimulated prolactin release was not enhanced by 1,25-(OH)2D3. We conclude that the active vitamin D metabolite, 1,25-(OH)2D3, caused a time- and dose-dependent increase in [3H]MeTRH binding. The effect was vitamin D metabolite-specific and resulted from an upregulation of the TRH receptor. Further studies are needed to determine the functional significance of this novel finding. | {
"pile_set_name": "PubMed Abstracts"
} |
Test of the usefulness of a paradigm to identify potential cardiovascular liabilities of four test articles with varying pharmacological properties in anesthetized guinea pigs.
The evaluation of proarrhythmic and hemodynamic liabilities for new compounds remains a major concern of preclinical safety assessment paradigms. Contrastingly, albeit functional liabilities can also translate to clinical morbidity and mortality, lesser preclinical efforts are focused on the evaluation of drug-induced changes in inotrope and lusitrope, particularly in the setting of concomitant hemodynamic/arrhythmic liabilities. This study aimed to establish the feasibility of an anesthetized guinea pig preparation to assess functional liabilities in the setting of simultaneous drug-induced electrocardiographic/hemodynamic changes, by evaluating the effects of various compounds with known cardiovascular properties on direct and indirect indices of left ventricular function. In short, twenty nine male guinea pigs were instrumented to measure electrocardiograms, systemic arterial pressure, and left ventricular pressure-volume relationships. After baseline measurement, all animals were given intravenous infusions of vehicle and two escalating concentrations of either chromanol 293B (n = 8), milrinone (n = 6), metoprolol (n = 7), or nicorandil (n = 8) for 10 minutes each. In all cases, these compounds produced the expected changes. The slope of preload-recruitable stroke work (PRSW), a pressure-volume derived load independent index, was the most sensitive marker of drug-induced changes in inotropy. Among the indirect functional indices studied, only the "contractility index" (dP/dtmax normalized by the pressure at its occurrence) and the static myocardial compliance (ratio of end diastolic volume and pressure) appeared to be adequate predictors of drug-induced changes in inotropy/lusitropy. Overall, the data confirms that both electrophysiological and mechanical liabilities can be accurately assessed in an anesthetized guinea pig preparation. | {
"pile_set_name": "PubMed Abstracts"
} |
New autosomal recessive syndrome of progressive sensorineural hearing loss and cataracts: report on two Brazilian patients.
We report on two sisters with cataracts and progressive sensorineural hearing loss, starting in infancy. They were born to consanguineous parents, and there were no similar cases in the family. To our knowledge this is the first report on this autosomal recessive condition. Clinical and genetic aspects are discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Recurrent tears following successful retinal detachment surgery.
In 17 cases of recurrent retinal tears occurring after successful retinal detachment surgery, the new tears developed on or near the treated primary tear in seven cases and away from the treated tear in ten cases. It took an average of 25.6 months for the second tears to develop, and almost all of the recurrent tears were the same distance from the limbus as the primary tear. The benefit of the 360 degree encircling band and the relationship of the thermal injury to production of a second tear is discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Attainment of low-density lipoprotein cholesterol goal after endovascular treatment is associated with reduced cardiovascular events in patients with peripheral arterial disease.
The relationship between attainment of low-density lipoprotein cholesterol (LDL-C) levels and clinical outcomes in patients with peripheral arterial disease (PAD) has received little attention. We sought to investigate clinical outcomes in relation to attainment of LDL-C goals in patients with PAD after endovascular treatment. We reviewed 342 PAD patients treated with endovascular therapy from 2010 through 2012. We categorized patients into two groups based on the attained LDL-C levels at short-term follow-up (mean, 4.8 ± 2.8 months): group A (n = 160), with LDL-C <70 mg/dL; and group B (n = 182), with LDL-C ≥70 mg/dL. The primary end point was major adverse cardiovascular events (MACEs), a composite of all-cause death, nonfatal myocardial infarction, and stroke. Baseline characteristics were similar between group A and group B except for obstructive pulmonary disease (0% vs 7%; P = .001). More patients in group A received statin therapy than those in group B (93% vs 76%; P < .001). MACEs (4% vs 10%; P = .002) and all-cause mortality (2% vs 7%; P = .007) occurred less frequently in group A than in group B at 2 years. A Cox proportional hazards multivariate regression model identified attainment of LDL-C goal <70 mg/dL at short-term follow-up as an independent predictor of reduced MACEs (hazard ratio, 0.25; 95% confidence interval, 0.09-0.67; P = .006) along with age as a predictor of increased MACEs (hazard ratio, 1.04; 95% confidence interval, 1.00-1.08; P = .031). Attainment of LDL-C goal <70 mg/dL at short-term follow-up is an independent predictor of reduced mortality and cardiovascular events after endovascular therapy in patients with PAD. | {
"pile_set_name": "PubMed Abstracts"
} |
[Animal experimental studies on immunogenicity, humoral response and danger of anaphylaxis in parenteral administration of hyaluronidase].
The widespread intravenous application of hyaluronidase rises questions for its potential immunogenicity, formation of humoral antibodies, and danger of anaphylaxis. In experiments on 21 rabbits and 40 rats, the authors searched for precipitating antibodies after subcutaneous, intramuscular, and intravenous application of hyaluronidase in doses equivalent to the human. Intravenous and intramuscular shots of 150 to 75 000 IU of Hylase were applied in order to test anaphylaxis. By all proving procedures antibodies against Hylase were found. The formation of antibodies occurred earlier and in higher concentrations after subcutaneous and intramuscular application. The antibodies belonged to the IgG group. One third of the animals showed anaphylactic responses at doses which were 13 to 630 times as high. 26 per cent of human patients developed antibodies after application of Hylase. No anaphylactic reactions were observed in 17 patients with antibodies when intravenous application of hyaluronidase was continued. In the dosage used in the man anaphylactic response is obviously rare though it is possible. | {
"pile_set_name": "PubMed Abstracts"
} |
Exploratory Factor Analysis With Small Sample Sizes.
Exploratory factor analysis (EFA) is generally regarded as a technique for large sample sizes (N), with N = 50 as a reasonable absolute minimum. This study offers a comprehensive overview of the conditions in which EFA can yield good quality results for N below 50. Simulations were carried out to estimate the minimum required N for different levels of loadings (λ), number of factors (f), and number of variables (p) and to examine the extent to which a small N solution can sustain the presence of small distortions such as interfactor correlations, model error, secondary loadings, unequal loadings, and unequal p/f. Factor recovery was assessed in terms of pattern congruence coefficients, factor score correlations, Heywood cases, and the gap size between eigenvalues. A subsampling study was also conducted on a psychological dataset of individuals who filled in a Big Five Inventory via the Internet. Results showed that when data are well conditioned (i.e., high λ, low f, high p), EFA can yield reliable results for N well below 50, even in the presence of small distortions. Such conditions may be uncommon but should certainly not be ruled out in behavioral research data. ∗ These authors contributed equally to this work. | {
"pile_set_name": "PubMed Abstracts"
} |
Estimating the public costs of teenage childbearing.
A formula for making national, state and local estimates of the cost to the public of teenage childbearing is derived from a review of 12 studies. The formula is then applied to U.S. data. The calculations yield a single-year cost for 1985 of $16.65 billion paid through three programs--Aid to Families with Dependent Children, food stamps and Medicaid--for women who first gave birth as teenagers. The calculations also show that the public will pay an average of $13,902 over the next 20 years for the family begun by each first birth to a teenager in 1985 and $5.16 billion over the same period for the families of all teenagers experiencing a first birth in 1985. If all teenage births were delayed until the mother was 20 or older, the potential savings to the public would be $5,560 for each birth delayed and $2.06 billion for the entire cohort of teenagers who would otherwise have had a first birth in 1985. | {
"pile_set_name": "PubMed Abstracts"
} |
Clinician screening and treatment of alcohol, drug, and mental problems in primary care: results from healthcare for communities.
We sought to estimate national rates of screening and treatment of alcohol, drug, and mental (ADM) problems in primary care. This was a cross-sectional survey administered from 1997 to 1998. Our study included a nationally representative household probability sample of 7301 primary care patients. We used patient self-reports from a telephone survey to estimate rates of screening and treatment of common ADM problems, to examine the types of screening and treatment received, and to investigate adherence with treatment recommendations. Covariates included measures of ADM conditions, physical health, and sociodemographic indicators. Among adult primary care patients, 38.6% (95% confidence intervals [CI] 37.2-40.0) reported clinician screening for an ADM problem. Alcohol or drug screening occurred more frequently (28.3%; 95% CI 27.0-29.6) than screening for depression and anxiety (21.2%; 95% CI 20.1-22.2). Among those screened, 30.1% (95% CI; 27.8-32.4) reported ADM treatment in primary care. Medications (16.4%; 95% CI 14.3-18.5) and counseling (18.2%; 95% CI 16.1-20.3) were the most common treatments. Rates of screening were higher among individuals with ADM disorders, the young and middle aged, and the college educated. Treatment rates were higher among individuals with ADM disorders. Substantial effort is expended screening and treating common ADM problems in primary care, and these efforts are targeted towards those with ADM disorders. However, only about half of individuals with an ADM disorder report being screened, and among this group, about 60% report receiving any treatment. | {
"pile_set_name": "PubMed Abstracts"
} |
Nipple-areola transposition by the superolateral-rotation pedicle technique in reduction mammaplasty: surgical description.
We report on a modified nipple-aerola transposition, employing a superolateral dermoglandular pedicle for primary use in reduction mammaplasty. We have found the method to be safe, technically simple, and quick. The cosmetic results have been satisfactory with a high rate of consistency in appearance. | {
"pile_set_name": "PubMed Abstracts"
} |
Endogenous factors and mechanisms of renoprotection and renal repair.
An imbalance between renal damaging molecules and nephroprotective factors contributes to the development and progression of kidney diseases. Molecules with renoprotective properties might serve as biomarkers, drug targets as well as therapeutic options themselves. For this review, we generated a set of renoprotective factors based on GeneRIF (Gene Reference Into Function) information available at NCBI's PubMed. The final set of manually curated renoprotective factors was investigated with respect to tissue-specific expression, subcellular location distribution and involvement in biological processes using information from gene ontology as well as information from protein-protein interaction databases. We furthermore investigated the factors in the context of clinical trials of renal disease and diabetes. One hundred and ninety-three factors could be retrieved from the set of GeneRIFs on nephroprotection and renal repair. A large number of factors were either secretory molecules or plasma membrane receptors. Next to the elevated expression in renal tissue, also higher expression in connective tissue and pancreas was observed. The proteins could be assigned to the broad functional categories of cell proliferation and signalling, inflammatory response, apoptosis, blood pressure regulation as well as cellular response to different kinds of insults such as hypoxia, heat or mechanical stimulus. Eight factors are studied in clinical trials with additional ones being targeted by compounds. We have generated a set of renoprotective factors based on the literature information, which was functionally annotated and evaluated with respect to tested compounds in kidney disease and diabetes clinical trials. | {
"pile_set_name": "PubMed Abstracts"
} |
Retrograde movement of digesta in the duodenum of the chick: extent, frequency, and nutritional implications.
Movement of digesta from the duodenum to the gizzard of chicks was assessed by injection of 99mTc-diethyl-triamino-pentaacetic acid via an indwelling cannula in the hepatic bile duct. The change in location of isotope with time was followed with a Gamma Camera. About 40% of the injected isotope refluxed to the gizzard within 2 minutes of injection. Clearance of the isotope from the gizzard had a T1/2 of some 20 minutes. Some possible implications of retrograde movement of digesta were examined. Cholesterol, bile salts and pancreatic enzymes were found in the gizzard at 10% to 20% of duodenal concentrations. The proteolysis and lipolysis in the gizzard and duodenum were determined in chicks fed a duet containing 91Y as a non-absorbed reference substance. Thirty percent of the feed triglycerides were found hydrolysed in the gizzard as compared to 50% to 60% in the duodenum. Proteins were 30% to 50% trichloroacetic acid soluble in the gizzard reaching almost 70% in the duodenum. A small net secretion of both fatty acids and protein was observed in the gizzard, probably due to reflux of endogenous secretions from the duodenum. The nutritional significance of these results is discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Clinical characteristics of heart disease patients with a good prognosis in spite of markedly increased plasma levels of type-B natriuretic peptide (BNP): anomalous behavior of plasma BNP in hypertrophic cardiomyopathy.
Although it is not rare to encounter patients with plasma B-type natriuretic peptide (BNP) levels unequivalent to the severity of heart failure (HF), there has been little investigation to clarify the causative background of this phenomenon. Among the 1,838 outpatients whose plasma BNP was measured, persistently increased levels of BNP above 500 pg/ml was observed for more than 6 months in 14 subjects with few HF symptoms. Among these, all of 4 patients without any following cardiac events (E-/high) for 12 months showed hypertrophic nonobstructive cardiomyopathy (HNCM). When we compared the clinical parameters of these patients with those of 22 HNCM patients without any following cardiac events whose plasma BNP levels were less than 200 pg/ml, there were only 2 clinical characteristics to be distinguished: (i) plasma renin activity (PRA) and norepinephrine (NE) levels were low in spite of markedly increased levels of plasma BNP in E-/high HNCM; and (ii) echocardiographic investigation revealed that only global left atrial fractional shortening was significantly lower in E-/high HNCM. Plasma BNP levels do not always reflect the severity of HF in HNCM. It might be considered to utilize other clinical parameters such as NE and PRA to recognize HF severity in such patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Current relevance of incomplete synthesis and neo-synthesis for cancer-associated alteration of carbohydrate determinants--Hakomori's concepts revisited.
Incomplete synthesis and neo-synthesis are two major concepts for cancer-associated alterations of cell surface carbohydrate determinants, formulated by Hakomori and collaborators almost 25 years ago. These concepts are still as relevant and useful as ever for cancer-associated alteration of carbohydrate determinants. Incomplete synthesis of carbohydrate determinants occurs through the epigenetic silencing of glycogenes through DNA methylation and/or histone modification in the early stage cancers. The natural selection of more malignant cancer cells occurs through acquisition of hypoxia resistance by constitutively activated hypoxia inducible factors (HIFs) in the advanced stages of cancers. HIFs induce transcription of several important glycogenes, and lead to neo-synthesis of carbohydrate determinants. For instance, expression of sialyl Lewis A/X is induced by epigenetic silencing of glycogenes in the early stages, and is further accelerated in the advanced stages by hypoxia-induced transcription of several glycogenes. Expression of GM2 ganglioside is induced in cancers by altered glycosyltransferase activities, and its N-glycolyl sialic acid content increases by hypoxia-induced transcription of a sialic acid transporter gene. N-glycolyl GM2 thus reflects two cancer-associated genetic abnormalities in a single determinant, and has high cancer specificity. Every carbohydrate determinant is synthesized through multiple steps, each of which is affected by cancer-associated genetic abnormality. Superiority of carbohydrate determinants as cancer-specific molecules over protein determinants is demonstrated in that a single carbohydrate determinant can reflect multiple cancer-associated genetic abnormalities. | {
"pile_set_name": "PubMed Abstracts"
} |
One-pot synthesis of phenylphosphonic acid imprinted polymers for tyrosine phosphopeptides recognition in aqueous phase.
The tyrosine phosphorylation of proteins plays a vital role in signal transduction pathways. The highly selective enrichment of tyrosine phosphopeptides remains a significant challenge in this area of research because of the low levels of tyrosine phosphorylation in cells. Herein, we report the development of a novel molecularly imprinted polymer (MIP)-based method for the recognition of tyrosine phosphopeptides in aqueous media using an epitope approach. Phenylphosphonic acid, which has been regarded the "epitope" of phosphotyrosine, was used as a template, and commercially available zinc acrylate was used as a functional monomer to prepare the MIP. The one-pot synthetic process was simple, efficient, and the resulting MIPs were low-cost, robust, and recyclable. The MIP demonstrated significant higher levels of adsorption capacity and selectivity for phenylphosphonic acid than the non-imprinting polymer (NIP) over its structural analog benzoic acid. The MIP was also used as a molecular receptor to recognize tyrosine phosphopeptides in aqueous media, and showed a clear preference for tyrosine phosphopeptides over interfering serine peptides compared to TiO2. These results revealed the feasibility of the use of MIPs to effectively mimic the epitope approach, and provided a promising alternative to the immunoaffinity techniques commonly used for capturing tyrosine phosphopeptides. | {
"pile_set_name": "PubMed Abstracts"
} |
Role of Leptin and SOCS3 in Inhibiting the Type I Interferon Response During Obesity.
Obesity provokes an imbalance in the immune system, including an aberrant type I interferon response during some viral infections and after TLR stimulation. SOCS3 overexpression and altered systemic leptin levels could be responsible for the reduced type I interferon production in people with obesity and, eventually, significantly increase the risk of viral infection. The aim of this study was to determine whether SOCS3- and leptin-induced tolerance are responsible for the reduced type I interferon production in people with obesity. SOCS3 overexpression in PBMCs from people with obesity was inhibited with the small interfering RNA (siRNA) assay, and leptin-induced tolerance was evaluated in PBMCs from non-obese volunte\ers and U937 cells treated with TLR ligands. SOCS3, but not SOCS1, gene silencing via siRNA increased the type I interferon response in PBMCs obtained from people with obesity. On the other hand, leptin induced SOCS3 expression and inhibited type I interferons in PBMCs from healthy donors and in U937 monocytes stimulated with TLR ligands. Taken together, these results demonstrate that reduced type I interferon production in obesity is caused by SOCS3 overexpression as well as tolerance induced by leptin. Here, we demonstrate a key role of leptin and SOCS3 in inhibiting the type I interferon response during obesity. | {
"pile_set_name": "PubMed Abstracts"
} |
In situ synthesis of Na2Ti7O15 nanotubes on a Ti net substrate as a high performance anode for Na-ion batteries.
Na2Ti7O15 nanotubes on a Ti net substrate were fabricated for the first time and used directly as a binder-free anode for Na-ion batteries. This material exhibited high reversible capacity and excellent stability which might be due to its unique characteristics including the porous substrate, nanoscale large surface area, nanotube structure and so on. | {
"pile_set_name": "PubMed Abstracts"
} |
The value of endothelium dependent vasodilatation in diagnosing coronary artery disease and its comparison with the results of routine diagnostic tests.
To determine the predictive value of flow-mediated vasodilation (FMD) compared with angina pectoris, exercise electrocardiography, and myocardial perfusion imaging (MPI). This study was carried out in Shahid Madani Heart Center, Tabriz, Iran from April 2004 to September 2006. A total of 92 patients with chest pain syndrome were enrolled in this study. Using high resolution ultrasound system endothelial function was evaluated, and the result of the flow-mediated dilation (FMD%) was defined as the percent change in the internal diameter of the brachial artery during reactive hyperemia related to baseline. Coronary artery disease (CAD) was documented in 77 (83.7%) patients. The percentage of FMD was lower in patients with CAD compared with those +/- 4.61, p=0.001). In comparison with typical anginal chest pain (sensitivity 46.7%, specificity 80%), exercise stress test (sensitivity 75%, specificity 60%), and MPI (sensitivity 96.5, specificity 55.6%) the receiver operator characteristic curve showed the percentage FMD optimal cut-off value as </=7.41 with a sensitivity of 87.0%, specificity of 66.7%, negative predictive value of 93.0%, and positive predictive value of 50%. In patients with chest pain syndrome, the FMD is a sensitive indicator of CAD with moderate specificity that is unable to predict accurately the extent and severity of it. | {
"pile_set_name": "PubMed Abstracts"
} |
Combined photon and electron three-dimensional conformal versus intensity-modulated radiotherapy with integrated boost for adjuvant treatment of malignant pleural mesothelioma after pleuropneumonectomy.
The optimal technique for postoperative radiotherapy (RT) after extrapleural pleuropneumonectomy (EPP) of malignant pleural mesothelioma (MPM) remains debated. The data from 8 right-sided and 9 left-sided consecutive cases of MPM treated with RT after radical EPP were reviewed. Of the 17 patients, 8 had been treated with three-dimensional (3D) conformal RT (3D-CRT) and 9 with intensity-modulated RT (IMRT) with 6-MV photons. The clinical outcome and adverse events were assessed. For comparative planning, each case was replanned with 3D-CRT using photons and electrons or with IMRT. Homogeneity, doses to the organs at risk, and target volume coverage were analyzed. Both techniques yielded acceptable plans. The dose coverage and homogeneity of IMRT increased by 7.7% for the first planning target volume and 9.7% for the second planning target volume, ensuring >or=95% of the prescribed dose compared with 3D-CRT (p < 0.01). Compared with 3D-CRT, IMRT increased the dose to the contralateral lung, with an increase in the mean lung dose of 7.8 Gy and an increase in the volume receiving 13 Gy and 20 Gy by 20.5% and 7.2%, respectively (p < 0.01). A negligible dose increase to the contralateral kidney and liver was observed. No differences were seen for the spinal cord and ipsilateral kidney. Two adverse events of clinical relevant lung toxicity were observed with IMRT. Intensity-modulated RT and 3D-CRT are both suitable for adjuvant RT. IMRT improves the planning target volume coverage but delivered greater doses to the organs at risk. Rigid dose constraints for the lung should be respected. | {
"pile_set_name": "PubMed Abstracts"
} |
Effect of sildenafil, a phosphodiesterase-5 inhibitor, on oesophageal peristalsis and lower oesophageal sphincter function in cats.
The propagation of oesophageal peristaltic contractions and lower oesophageal sphincter (LOS) relaxation depends on neural release of nitric oxide (NO) which acts to increase intracellular cGMP. Sildenafil, a phosphodiesterase-5 inhibitor that increases cGMP, reduces basal LOS pressure in patients with achalasia. We investigated the effect of sildenafil on the propagation of oesophageal contractions and LOS relaxation in the cat. Oesophageal manometry was performed in five cats under light sedation. Peristaltic contractions were monitored at 1, 2, 3, 4 and 8 cm proximal to the LOS, at the LOS using a Dent sleeve, and at 3 cm distal to the upper oesophageal sphincter. Swallow-induced oesophageal contractions and LOS relaxation were recorded during 30 min before and 30 min after intravenous administration of sildenafil. Sildenafil reduced the amplitude of oesophageal contractions only in the smooth muscle oesophagus. The latency from swallow to distal oesophageal contractions was significantly delayed. LOS pressure was significantly reduced but the relaxation nadir was not modified by sildenafil. Sildenafil has profound effects on oesophageal motility: it modifies propagation and amplitude of oesophageal contractions and reduces LOS pressure. Slowing down the propagation of contractions in the transitional zone between the striated and smooth muscle can be a useful tool in patients with segmental aperistalsis or intermittent simultaneous contractions, while the effect on the LOS can benefit patients with achalasia. | {
"pile_set_name": "PubMed Abstracts"
} |
Differentiating specialists and generalists within college students' social support networks.
In order to examine the relationships among social network structure, types of social support, and determinants of support satisfaction, an alternative method was used to score the Social Support Questionnaire (SSQ). Factor analysis procedures suggested that college students' (N=198) social networks consisted of four groups: nuclear family, other family, friends, and others. Satisfaction with support was positively related to the proportion of the network occupied by nuclear family and negatively related to the proportion of friends in the network. Evidence was found for the presence of both support specialists and support generalists in the networks of the college students. These results are discussed from a developmental perspective with attention to the implications for interventions. | {
"pile_set_name": "PubMed Abstracts"
} |
Labour and delivery routines in English consultant maternity units.
A survey of midwifery policies in English Health Districts shows that consultant maternity units vary in the extent to which aspects of care during labour and at delivery come within the scope of unit policies. In addition, the details of policies vary considerably, to the extent that a midwife moving from one maternity unit to another might find herself dealing with a policy that was diametrically opposed to that in the unit from which she had come. The implications of these variations are discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Stable and sensitive flow-through monitoring of phenol using a carbon nanotube based screen printed biosensor.
A stable and sensitive biosensor for phenol detection based on a screen printed electrode modified with tyrosinase, multiwall carbon nanotubes and glutaraldehyde is designed and applied in a flow injection analytical system. The proposed carbon nanotube matrix is easy to prepare and ensures a very good entrapment environment for the enzyme, being simpler and cheaper than other reported strategies. In addition, the proposed matrix allows for a very fast operation of the enzyme, that leads to a response time of 15 s. Several parameters such as the working potential, pH of the measuring solution, biosensor response time, detection limit, linear range of response and sensitivity are studied. The obtained detection limit for phenol was 0.14 x 10(-6) M. The biosensor keeps its activity during continuous FIA measurements at room temperature, showing a stable response (RSD 5%) within a two week working period at room temperature. The developed biosensor is being applied for phenol detection in seawater samples and seems to be a promising alternative for automatic control of seawater contamination. The developed detection system can be extended to other enzyme biosensors with interest for several other applications. | {
"pile_set_name": "PubMed Abstracts"
} |
Low serum vitamin D is independently associated with unexplained elevated ALT only among non-obese men in the general population.
There are inconsistent findings on the association between human non-alcoholic fatty liver disease (NAFLD) and vitamin D, perhaps due to insufficient specificity for gender and obesity status. We aimed to assess whether serum levels of 25-hydroxyvitamin D are associated with unexplained elevated alanine aminotransferase (ALT) in general population across gender and body mass index (BMI) levels. A cross-sectional analysis of a population-based cohort with a nationwide-distribution using electronic medical database. The population consisted of individuals aged 20-60 years who underwent blood tests for ALT and vitamin D. A total of 82,553 subjects were included (32.5% men, mean age 43.91±10.15 years). The prevalence of elevated ALT was higher among men and women with vitamin D insufficiency or deficiency, but in multivariate analysis, adjusting for: age, BMI, serum levels of glucose, total cholesterol, triglycerides, statin use and season, only the association among men remained significant for the vitamin D deficiency category (OR=1.16, 95%CI 1.04-1.29, P=0.010). Stratification by BMI revealed that only among normal weight and overweight men vitamin D deficiency was associated with elevated ALT (OR=1.27, 95%CI 1.01-1.59, P=0.041 and OR=1.27, 95%CI 1.08-1.50, P=0.003, respectively). No independent association was shown among women at all BMI categories. In a "real-life" general population, the association between vitamin D deficiency and unexplained elevated ALT is specific for non-obese men. The clinical significance of vitamin D for human NAFLD should be further elucidated with attention for a modifying effect of gender and adiposity. | {
"pile_set_name": "PubMed Abstracts"
} |
Gefitinib and chemotherapy combination studies in five novel human non small cell lung cancer xenografts. Evidence linking EGFR signaling to gefitinib antitumor response.
The epidermal growth factor receptor (EGFR) signaling pathway is often activated in NSCLC, and thus represents a promising therapeutic target. We studied the antitumor activity of gefitinib (Iressa), an orally active EGFR-tyrosine kinase inhibitor, alone and in combination with standard chemotherapy in 5 recently established human NSCLC xenografts with wild-type EGFR. Mice were treated with 2 protocols of chemotherapy based on cisplatin (CDDP) combined with either gemcitabine (GEM) or vinorelbine (VNR). Gefitinib alone significantly inhibited tumor growth (TGI) in 4 of the 5 tumor xenografts (mean TGI of 58%, range: 25-70%). CDDP+VNR alone failed to achieve any significant responses, while CDDP+GEM achieved significant responses in 2 xenografts (TGI of 93 and 47%). Addition of gefitinib to CDDP+GEM potentialized chemotherapy in the 3 CDDP+GEM-resistant xenografts, but did not potentialize the CDDP+VNR combination. The effect of gefitinib treatment on the activity of extra cellular-regulated kinase (Erk), Akt, JNK and p38 kinases was assessed in IC9LC11 and IC1LC131, two NSCLC xenografts selected for their sensitivity and resistance to gefitinib, respectively. In IC9LC11, gefitinib strongly inhibited Erk, Akt and Jnk phosphorylation, but P38 remained active. Inversely, in IC1LC131, Erk and Akt pathways remained active, while Jnk and P38 pathways were inhibited by gefitinib. The data indicate that the antitumor activity of gefitinib in NSCLC, alone or in combination with chemotherapy, is tumor-dependent and is influenced by downstream signaling events independent of EGFR status. | {
"pile_set_name": "PubMed Abstracts"
} |
Recurrent abdominal laxity following interpositional human acellular dermal matrix.
Repair of large complex abdominal hernias with significant loss of domain requires component separation in combination with either a synthetic or biologic interpositional material. We previously described an algorithm for complex abdominal hernia repair, which incorporates Alloderm as an interpositional material and selective use of prolene mesh as an overlay. We now report recurrent laxity in a series of patients who were repaired with interpositional Alloderm alone without prolene mesh overlay. We reviewed all patients who underwent repair of massive ventral hernias and identified 7 patients who presented with abdominal wall laxity following component separation with interpositional Alloderm alone. All patients developed laxity within 12 months and required a secondary procedure. At the time of re-exploration, severe attenuation in the Alloderm was noted. The segment was excised, the edges closed primarily, and prolene mesh was placed as an onlay. Although Alloderm has been reported to be an effective biologic material for abdominal hernia reconstruction, we have noted significant laxity requiring secondary intervention. | {
"pile_set_name": "PubMed Abstracts"
} |
Characterization of the adrenal 11 beta-hydroxylase in inbred salt-sensitive and resistant rats.
Rats have been bred for susceptibility and resistance to the hypertensive effect of dietary salt (S/JR & R/JR). S/JR have an abnormal adrenal steroid 11 beta,18-hydroxylase activity resulting in increased production of 18-OH-DOC. S/JR also produce increased quantities of 19-nor-DOC, which may be related, since the 11 beta,18-hydroxylase also catalyzes the 19-hydroxylation of DOC, a pivotal step in 19-nor-DOC biosynthesis. The purpose of the present studies was to further characterize the mutant S/JR adrenal steroid 11 beta,18-hydroxylase. Preliminary studies are also presented on assessing the renal 19-desmolase, the last step in 19-nor-DOC biosynthesis. Adrenal glands were harvested from R/JR and S/JR and prepared for incubation studies, protein immunoblotting, and RNA analysis. Kidneys from Sprague-Dawley rats were also used for isolated renal perfusion studies. Both S/JR and R/JR strains had a single immunostaining band for 11 beta,18-hydroxylase at 51,000 molecular weight which were equal in intensity. Both strains had a single RNA transcript at 4.3 kilobases which hybridized with equal intensity to the bovine cDNA (pB11-9). The Km for 11 beta- and 18-hydroxylation was identical within strains but was different between strains. The Km for 19-hydroxylation was different between S/JR and R/JR, and was much greater than 11 beta- and 18-hydroxylation in both strains. This suggests that the catalytic site for 19-hydroxylation is different than that for 11 beta- and 18-hydroxylation and that the S/JR enzyme binds the substrate with higher affinity than the R/JR enzyme. In the isolated perfusion studies the rat kidneys converted 80% of 19-oxo-DOC to either 19-oic-DOC or 19-nor-DOC. These data demonstrate that the difference in S/JR enzyme activity is probably due to a point mutation in the enzyme or to a change in a regulatory protein. | {
"pile_set_name": "PubMed Abstracts"
} |
Bhargavaea changchunensis sp. nov. isolated from soil in China.
A Gram-staining-positive, aerobic, rod-shaped (201802YP6T) bacteria was isolated from soil, Northeast of China. Growth occurred at 10-40 °C (optimum 25-30 °C), at pH 6.0-8.0 (optimum 7.0) and at 0-2% NaCl. Based on 16S rRNA gene sequence analysis, the nearest phylogenetic neighbors of strain 201802YP6T were identified as Bhargavaea cecembensis DSE10T (99.52%), Bhargavaea beijingensis ge10T (99.45%), Bhargavaea indica KJW98T (99.45%), Bhargavaea ullalensis ZMA19T (98.81%), and Bhargavaea ginsengi ge14T (98.76%). Levels of similarity among strain 201802YP6T and other Bhargavaea species were lower than 98.76%. GyrB amino acid sequence-based analysis supported the phylogenetic position and also distinguished strain 201802YP6T from the other species of the genus Bhargavaea. DNA-DNA hybridization values between strain 201802YP6T and B. cecembensis, B. beijingensis, B. indica, B. ullalensis, B. ginsengi were 43.5%, 43%, 32.5%, 30.5% and 20.4%, respectively. The DNA G + C content of strain 201802YP6T was 51.23 mol%. The average nucleotide identity (ANI) of the draft genome was 87.04% to B. cecembensis DSE10T. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, glycolipids, phosphatidylethanolamine, and phosphatidyllipid. The predominant menaquinone was MK-8. The major fatty acids were iso-C15:0 (39.91%), anteiso-C15:0 (28.86%), anteiso-C17:0 (6.30%) and C16:0 (6.13%). On the basis of the phylogenetic analysis, chemotaxonomic data, physiological characteristics and DNA-DNA hybridization data, strain 201802YP6T represents a novel species of the genus Bhargavaea, for which the name Bhargavaea changchunensis sp. nov. is proposed. The type strain is 201802YP6T (= CGMCC 1.13508T = KCTC 33975T). | {
"pile_set_name": "PubMed Abstracts"
} |
Comparing the characteristics, utilization, efficiency, and outcomes of VA and non-VA inpatient care provided to VA enrollees: a case study in New York.
To compare the characteristics, utilization, and outcomes of Veterans Health Administration (VA) and non-VA inpatient care provided to VA enrollees in New York. Using VA and New York State administrative and clinical databases, we conducted a retrospective study examining 110,716 residents of New York State who were enrolled in the VA and had 266,869 inpatient admissions in VA and non-VA hospitals in New York. For each admission, we determined the system of care used (VA or non-VA), patient demographics, and characteristics of the admission, and we calculated VA patients' relative reliance on the VA for inpatient care. For each Major Diagnostic Category (MDC), we examined reliance, patient characteristics, and lengths-of-stay for 2 groups: veterans who were younger than age 65 and those age 65 or older. Fifty-three percent of younger patients' inpatient admissions were in the VA, whereas 32% of older patients' were; however, relative reliance on the VA varied dramatically across the 19 MDCs examined. Across age groups, patients admitted to VA hospitals were younger, less likely to be white, and less likely to live in a rural setting. Those using VA hospitals had lower Charlson scores and received less complex care. For both age groups and across all MDCs, admissions to VA hospitals had substantially higher diagnosis related group-specific observed-to-expected lengths-of-stay. Younger and older veterans use VA and non-VA hospitals differently for inpatient services. Comprehensive inpatient datasets could inform planners about VA's service market and VA managers about achievable performance benchmarks that are relevant to VA's service population. | {
"pile_set_name": "PubMed Abstracts"
} |
One-stage repair of skin and tendon digital defects using the arterialized venous flap with palmaris longus tendon: an additional four cases.
The use of the arterialized venous flap with a palmaris longus tendon transfer has previously been reported. Further trials of this technique were conducted in four patients to reconstruct complicated finger injuries involving loss of skin and extensor tendon. In contrast to the results of previous cases, those of recent cases are more encouraging. This technique may be the procedure of choice in patients with digital skin defects, where there are associated extensor tendon defects with exposed bone. | {
"pile_set_name": "PubMed Abstracts"
} |
Morphology Evolution of Polymer Blends under Intense Shear During High Speed Thin-Wall Injection Molding.
The morphology evolution under shear during different processing is indeed an important issue regarding the phase morphology control as well as final physical properties of immiscible polymer blends. High-speed thin wall injection molding (HSTWIM) has recently been demonstrated as an effective method to prepare alternating multilayered structure. To understand the formation mechanism better and explore possible phase morphology for different blends under HSTWIM, the relationship between the morphology evolution of polymer blends based on polypropylene (PP) under HSTWIM and some intrinsic properties of polymer blends, including viscosity ratio, interfacial tension, and melt elasticity, is systematically investigated in this study. Blends based on PP containing polyethylene (PE), ethylene vinyl alcohol copolymer (EVOH), and polylactic acid (PLA) are used as examples. Compatibilizer has also been added into respective blends to alter their interfacial interaction. It is demonstrated that dispersed phase can be deformed into a layered-like structure if interfacial tension, viscosity ratio, and melt elasticity are relatively small. While some of these values are relatively large, these dispersed droplets are not easily deformed under HSTWIM, forming ellipsoidal or fiber-like structure. The addition of a moderate amount of compatibilizer into these blends is shown to be able to reduce interfacial tension and the size of dispersed phase, thus, allowing more deformation on the dispersed phase. Such a study could provide some guidelines on phase morphology control of immiscible polymer blends under shear during various processing methods. | {
"pile_set_name": "PubMed Abstracts"
} |
Dopamine fails to stimulate protein kinase C activity in renal proximal tubules of spontaneously hypertensive rats.
We have previously reported that dopamine-1 receptor-mediated activation of phospholipase C is diminished in renal cortical slices of spontaneously hypertensive rats. The present study was carried out to examine the effect of dopamine on protein kinase C (PKC), which is one of the enzymes involved in the signal-transduction pathway leading to dopamine-induced inhibition of Na+/K(+)-ATPase in the renal proximal tubule. Renal proximal tubule suspensions were obtained from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats of 10-12 weeks old. The tubules were incubated with dopamine in the presence or absence of DA-1 receptor antagonist SCH 23390. The PKC activity was measured by using a specific fluorescent peptide substrate (sequence, PKSRTLSVAAK). We found that dopamine produced a concentration-dependent increase in protein kinase C activity in the WKY rats, however, it failed to stimulate PKC activity in the SHR. Peak stimulation of 3.828 +/- 0.35 (ng/micrograms) protein in the WKY rats was observed at dopamine concentration of 1 microM, which was blocked in a concentration-dependent manner by SCH 23390 (0.25 microM). These results provide evidence that dopamine directly stimulates PKC activity via activation of DA-1 receptors in WKY rats. Furthermore, we discovered that dopamine fails to stimulate PKC activity in the SHR. This phenomenon may be responsible for the failure of dopamine to inhibit Na+/K(+)-ATPase activity in the hypertensive animals. | {
"pile_set_name": "PubMed Abstracts"
} |
Understanding Variation-Part 2: The Control Chart.
Both run and control charts can be used to answer the question "How will we know that a change is an improvement?". Run charts are advantageous at the start of an improvement effort, when little is known about the system and how it performs. Over time, transitioning to a control chart may provide more specific information and insight into the data being measured. The type of numeric data being collected helps guide the most appropriate choice of control chart. Control chart rules exist and should be used to determine if a change in the data represents common cause or special cause variation. Similar to run charts, it is important not to over- or under-react to a single point on a control chart. Control chart rules help quality improvers determine whether interventions being tested are having a meaningful impact on the system. | {
"pile_set_name": "PubMed Abstracts"
} |
Behavioral and neurochemical evaluation of phenylpropanolamine.
(+/-)-Phenylpropanolamine (PPA), a widely available anorectic and decongestant, was evaluated in several behavioral paradigms in rhesus monkeys and for central nervous system neurotoxicity in rats. PPA (1-30 mg/kg intragastric) reduced food intake in rhesus monkeys but was not self-administered i.v. (0.3-10 mg/kg/injection) by monkeys experienced in drug self-administration. PPA (30-100 mg/kg intragastric) resulted in amphetamine-like responding in two of four monkeys trained in a drug discrimination paradigm to discriminate d-amphetamine from saline. In rats, a 4-day injection regimen of high doses of PPA (200 and 400 mg/kg/day) resulted in approximately a 20% depletion of dopamine in the frontal cortex but failed to deplete dopamine, norepinephrine or serotonin in any other brain region studied. Thus, PPA is an effective anorectic in rhesus monkeys that, based upon drug discrimination results, would be expected to have limited amphetamine-like subjective effects and only at doses well in excess of effective anorectic doses. However, based upon self-administration results, PPA would not be predicted to have amphetamine-like dependence potential. Moreover, repeated administration of PPA did not produce the severe central nervous system neurotoxicity associated with many other amphetamine congeners. | {
"pile_set_name": "PubMed Abstracts"
} |
Time-Dependent Quantum Wave Packet Study of the Si + OH → SiO + H Reaction: Cross Sections and Rate Constants.
The dynamics of the Si(3P) + OH(X2Π) → SiO(X1Σ+) + H(2S) reaction is investigated by means of the time-dependent wave packet (TDWP) approach using an ab initio potential energy surface recently developed by Dayou et al. ( J. Chem. Phys. 2013 , 139 , 204305 ) for the ground X2A' electronic state. Total reaction probabilities have been calculated for the first 15 rotational states j = 0-14 of OH(v=0,j) at a total angular momentum J = 0 up to a collision energy of 1 eV. Integral cross sections and state-selected rate constants for the temperature range 10-500 K were obtained within the J-shifting approximation. The reaction probabilities display highly oscillatory structures indicating the contribution of long-lived quasibound states supported by the deep SiOH/HSiO wells. The cross sections behave with collision energies as expected for a barrierless reaction and are slightly sensitive to the initial rotational excitation of OH. The thermal rate constants show a marked temperature dependence below 200 K with a maximum value around 15 K. The TDWP results globally agree with the results of earlier quasi-classical trajectory (QCT) calculations carried out by Rivero-Santamaria et al. ( Chem. Phys. Lett. 2014 , 610-611 , 335 - 340 ) with the same potential energy surface. In particular, the thermal rate constants display a similar temperature dependence, with TDWP values smaller than the QCT ones over the whole temperature range. | {
"pile_set_name": "PubMed Abstracts"
} |
Improvements in event-related desynchronization and classification performance of motor imagery using instructive dynamic guidance and complex tasks.
The motor-imagery based brain-computer interface supplies a potential approach for motor-impaired patients, not only to control rehabilitation facilities but also to promote recovery from motor dysfunctions. To improve event-related desynchronization during motor imagery and obtain improved brain-computer interface classification accuracy, we introduce dynamic video guidance and complex motor tasks to the motor imagery paradigm. Eleven participants were included in the experiment; 64-channel electroencephalographic data were collected and analyzed during four motor imagery tasks with different guidance. Time-frequency analysis, spectral-time variation analysis, topographical distribution maps, and statistical analysis were utilized to analyze the event-related desynchronization patterns. Common spatial patterns were used to extract spatial pattern features and support vector machines were used to discriminate the offline classification accuracies in three bands (the alpha band, beta band, alpha and beta band) for comparison. The experimental outcomes showed that complex motor imagery tasks coupled with dynamic video guidance induced significantly stronger event-related desynchronization than other paradigms, which use simple motor imagery tasks or static guidance. Similar results were obtained during analysis of the motor imagery brain-computer interface classification performance; namely, the highest average classification accuracy in complex and dynamic guidance was improved by approximately 14%, compared with static guidance. For individually specified paradigms, all participants obtained a classification accuracy that exceeded or was equal to 87.5%. This study provides an optional route to enhance the event-related desynchronization activities and classification accuracy of a motor imagery brain-computer interface through optimization of motor imagery tasks and instructive guidance. | {
"pile_set_name": "PubMed Abstracts"
} |
Effect of calcium to reverse the electrocardiographic effects of hyperkalemia in the isolated rat heart: a prospective, dose-response study.
To determine: a) any heart site or tissue-specific differences in the response to increased perfusion potassium concentrations, and b) the cellular site (intracellular vs. extracellular) of the effect of calcium on reversing electrocardiographic effects of hyperkalemia. In vitro prospective, repeated-measures, dose-response study. University/medical school experimental physiology laboratory. Adult male Sprague-Dawley rats whose hearts were studied in an in vitro perfusion preparation. One group of hearts was perfused with modified Krebs-Henseleit physiologic salt solution onto which were superimposed infusions of concentrated potassium and/or calcium solutions. Infusion rates increased stepwise the respective ions in order to calculate increased concentrations through the course of the experiment. Calcium concentration was at either 4.0 or 5.4 mEq/L (2.0 or 2.7 mmol/L); potassium concentration was increased from 5.8 to 7.3, 8.0, 8.8, 10.2 and 11.8 mmol/L. Two more groups of hearts were perfused with Krebs-Henseleit solution containing the lower calcium concentration to which was added the calcium ionophore A23187 in one of two doses. A fourth group of hearts was perfused with Krebs-Henseleit solution containing the higher calcium concentration to which was added the a single dose of the calcium-channel blocking agent verapamil. We tested the effects of a series of ion and drug concentrations on epicardial EKG variables (atrial and ventricular rates, P-wave amplitude, PR interval, QRS complex amplitude and duration, and T-wave amplitude and duration). The effects of these variables were tested by increasing the ionized calcium in the perfusate of isolated rat hearts from 4.0 mEq/L (2.0 mmol/L) to 5.4 mEq/L (2.7 mmol/L) as perfusate potassium was increased stepwise from normal (5.8 mEq/L or mmol/L) to as high as 11.8 mEq/L (mmol/L). In addition, we studied the effect of adding the calcium ionophore A23187 to the perfusate with the lower ionized calcium concentration, and we also studied the effect of adding the calcium-channel blocking agent verapamil to the perfusate containing the higher ionized calcium while increasing the perfusate potassium concentration in a stepwise manner in each of the series. The higher calcium concentration (5.4 mEq/L or 2.7 mmol/L) prevented most of the adverse effects of the highest potassium concentration in the first drug-free series of experiments. When the calcium ionophore A23187 was added to the perfusate, most electrocardiographic variables remained normal even in the presence of a lower ionized calcium concentration. However, the higher ionized calcium concentration was not able to prevent electrical abnormalities in hearts perfused with high potassium when verapamil was in the solution. We conclude that the mechanism whereby calcium reverses the clinically observable electrocardiographic effects of hyperkalemia is an intracellular one. | {
"pile_set_name": "PubMed Abstracts"
} |
Changes in bacterial communities accompanied by aggregation in a fed-batch composting reactor.
The contents of fed-batch composting (FBC) reactors often aggregate after prolonged operation. This process leads to irreversible breakdown of the decomposition reaction and possible alteration of the bacterial communities. We compared the structures of bacterial communities in reactors under aggregate and optimal conditions. The results of 16S rRNA gene clone analysis showed that populations of the family Bacillaceae (such as Bacillus spp., Cerasibacillus spp., Gracilibacillus spp.), which dominate (98%) under optimal condition, were significantly decreased under aggregate condition. In contrast, populations of the family Staphylococcaceae considerably increased after aggregation and accounted for 53% of the total. Phylogenetic analysis also showed that anaerobes or facultative anaerobes related to Tetragenococcus halophilus, Atopostipes suicloacalis, Jeotgalicoccus pinnipedialis, and Staphylococcus spp. were dominant in the aggregates. These results suggested that aerobic Gram-positive bacteria mainly contributed to organic degradation and that aggregation created some anaerobic environment, which promoted the growth of bacterial communities usually not found in well-functioning FBC reactors. | {
"pile_set_name": "PubMed Abstracts"
} |
Maternal antibody reactivity to lymphocytes of offspring with autism.
The study examined whether maternal serum antibodies from mothers of autistic children preferentially bind to lymphocytes of their autistic children compared with unaffected siblings. In a previous study, maternal serum antibodies from mothers mediated cytotoxicity with complement to lymphocytes of their autistic children. Here, maternal serum antibody binding was examined by flow cytometry. We compared levels of mothers' serum binding against peripheral blood monocytes of their autistic children vs unaffected siblings. Because the level of binding to peripheral blood monocytes could be low, binding was examined in specific lymphocyte subpopulations. In 19 samples, the mean level of maternal serum immunoglobulin G binding to CD4 and CD8 T cells, B cells, natural killer cells, and macrophages was not significantly different from the mean level of binding to unaffected siblings. The percentages of different subpopulations were not significantly different between autistic children and unaffected siblings, although a trend (P < 0.1) emerged, i.e., autistic children displayed a higher percentage of natural killer cells and a lower percentage of B cells. These findings cast doubt on a direct effect of maternal antibodies, but do not preclude potential intrauterine pathogenic immune mechanisms in autism. | {
"pile_set_name": "PubMed Abstracts"
} |
Interleukin-6 in combination with its soluble IL-6 receptor sensitises rat skin nociceptors to heat, in vivo.
Interleukin-6 (IL-6) contributes to increased pain and hyperalgesia in inflamed tissue. We have investigated the effects of IL-6, alone or in combination with its soluble receptor (sIL-6R), on the sensitivity of nociceptors to noxious heat, using dermal microdialysis. Plasmapheresis membranes were inserted into the abdominal skin of adult male Wistar rats (n=46) and perfused with modified Ringer solution. After three control samples (20 min each), the skin area above the membrane was heated to 48 degrees C for 20 min. The stimulation was followed by two washout samples. The calcitonin gene-related peptide (CGRP) content of the dialysate was measured with an enzyme immunoassay. Heat stimulation provoked a significant CGRP increase in the dialysate. Intradermal application of IL-6 (200 ng ml-1) did not significantly alter heat-induced CGRP release. However, a significant sensitisation of the heat-induced CGRP release was observed when sIL-6R (25 ng ml-1) was applied, either alone or in combination with IL-6. Neutralisation of endogenous IL-6 with a sheep anti-rat IL-6 serum did not alter heat-induced CGRP release, but abolished the sIL-6R-mediated sensitising effect. We show that IL-6 in combination with its soluble receptor can sensitise nociceptors to heat and provide evidence for the constitutive expression of the signalling molecule gp130, but not of the IL-6-membrane-bound (specific) receptor, in nociceptors. | {
"pile_set_name": "PubMed Abstracts"
} |
The morphology and distribution of striate cortex terminals in the inferior and lateral subdivisions of the Macaca monkey pulvinar.
The origin of the various types of axon terminals in Macaca pulvinar remains uncertain because of the contradictory results obtained in EM degeneration studies. We have used EM-autoradiography to determine the morphology of terminals in the inferior and lateral pulvinar which originate from neurons in visual cortex. After injections of H3 proline into area 17, both the small diameter (RS) and the large diameter (RL) terminals containing round vesicles and making asymmetric contacts are labeled in the two pulvinar subdivisions. Labeled and unlabeled terminals are intermixed within the pulvinar focus which suggests that the dendrites of the same pulvinar neuron receive overlapping inputs from several cortical areas. Because only 5% of the pulvinar terminals are RLs (Ogren and Hendrickson, '79), and this small number of RLs originates from at least two visual cortical areas plus the superior colliculus (Partlow et al., '77), superior colliculus input to inferior pulvinar is small compared to the combined RS and RL cortical input. Together the findings from this study and the preceding paper (Ogren and Henderickson, '79), show that while pulvinar is typical of other thalamic nuclei in the structure of its neurons and synapses, it differs in that the input from subcortical structures is minimal. It is suggested that inferior and lateral pulvinar function principally as integrators of visula cortical information. | {
"pile_set_name": "PubMed Abstracts"
} |
Long-term treatment with leuprorelin for spinal and bulbar muscular atrophy: natural history-controlled study.
To evaluate the prognosis and progression of spinal and bulbar muscular atrophy (SBMA), a rare X-linked motor neuron disorder caused by trinucleotide repeat expansion in the AR (androgen receptor) gene, after long-term androgen suppression with leuprorelin acetate treatment. In the present natural history-controlled study, 36 patients with SBMA treated with leuprorelin acetate for up to 84 months (leuprorelin acetate-treated group; LT group) and 29 patients with SBMA with no specific treatment (non-treated group; NT group) were analysed. Disease progression was evaluated by longitudinal quantitative assessment of motor functioning using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and the modified Norris score. In addition, we selected two major clinical endpoint events, namely the occurrence of pneumonia requiring hospitalisation and death, to evaluate disease prognosis following long-term leuprorelin acetate treatment. In our analysis of the longitudinal disease progression using the random slope model, we observed a significant difference in the ALSFRS-R total score, the Limb Norris Score, and the Norris Bulbar Score (p=0.005, 0.026 and 0.020, respectively), with the LT group exhibiting a slower per-12-months decline compared with the NT group. As for the event analysis, the prognosis of the LT group was better in comparison to the NT group as for the event-free survival period (p=0.021). Long-term treatment with leuprorelin acetate appears to delay the functional decline and suppress the incidence of pneumonia and death in subjects with SBMA. | {
"pile_set_name": "PubMed Abstracts"
} |
Optimal oxidative folding of the novel antimicrobial cyclotide from Hedyotis biflora requires high alcohol concentrations.
Hedyotide B1, a novel cyclotide isolated from the medicinal plant Hedyotis biflora, contains a cystine knot commonly found in toxins and plant defense peptides. The optimal oxidative folding of a cystine knot encased in the circular peptide backbone of a cyclotide poses a challenge. Here we report a systematic study of optimization of the oxidative folding of hedyotide B1, a 30-amino acid cyclic peptide with a net charge of +3. The linear precursor of hedyotide B1, synthesized as a thioester by solid phase synthesis, was cyclized quantitatively by a thia-zip cyclization to form the circular backbone and then subjected to oxidative folding in a thiol-disulfide redox system under 38 different conditions. Of the oxidative conditions examined, the nature of the organic cosolvent appeared to be critical, with the use of 70% 2-propanol affording the highest yield (48%). The disulfide connectivity of the folded hedyotide was identical to that of the native form as determined by partial acid hydrolysis. The use of such a high alcohol concentration suggests that a partial denaturation may be necessary for the oxidative folding of a cyclotide with the inverse orientation of hydrophobic side chains that are externalized to the solvent face to permit the formation of the interior cystine core in the circularized backbone. We also show that synthetic hedyotide B1 is an antimicrobial, exhibiting minimal inhibitory concentrations in the micromolar range against both Gram-positive and -negative bacteria. | {
"pile_set_name": "PubMed Abstracts"
} |
Assessing alcohol problems in college students.
Alcohol abuse among college students is prevalent, yet few instruments with sound reliability and validity are available to assess these problems in this population. As part of a large, baseline assessment battery for a prospective study of offspring of alcoholics, the 27-item Young Adult Alcohol Problems Screening Test (YAAPST) was given to 490 freshmen at a large midwestern university; approximately 9 months later, 482 subjects completed the scale again. In addition to asking about such traditional problems as experiencing blackouts and driving while intoxicated, the YAAPST included specific items relating to college experiences (eg, getting into sexual situations that were later regretted, missing classes, and receiving lower grades than usual). The YAAPST was designed to assess these drinking consequences over two different time frames, lifetime and past year, and also to indicate the frequency of occurrence during the past year. Results indicated that the YAAPST is a unidimensional scale with good psychometric properties (good internal consistency and test-retest reliability). Three different approaches were used to demonstrate the validity of the YAAPST. Findings supported criterion validity (with interview-based alcohol abuse/dependence diagnoses as the criterion), concurrent validity (comparing the YAAPST with other drinking measures), and construct validity (correlating the YAAPST with etiologically relevant personality, motivational, and peer influence variables). The YAAPST is a promising screening instrument for alcohol problems in college students. It has excellent psychometric properties and the potential to provide a range of useful information to the clinician or researcher. | {
"pile_set_name": "PubMed Abstracts"
} |
Age-related changes in muscle.
Sarcopenia is a debilitating condition that occurs with senescence. The present study places this entity in the context of life expectancy, then discusses the mechanism of muscle loss. The findings show deficits in muscle protein synthesis with advancing age and suggest that these deficits are specific to certain muscle protein components. Synthesis rates of myosin heavy chain and mitochondrial protein decline with advancing age; however, there are no specific conclusions as to causation of these reduced muscle protein syntheses. The utility of protein dynamic measurements in evaluating potential therapies is discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Ultraviolet resonance Raman studies of quaternary structure of hemoglobin using a tryptophan beta 37 mutant.
Environmental changes of tyrosine and tryptophan residues of hemoglobin (Hb) upon its T to R transition of quaternary structure were investigated with ultraviolet resonance Raman (UVRR) spectroscopy excited at 235 nm. DeoxyHb A (T-form) showed a UVRR spectrum distinctly different from those of the ligated Hbs (R-form) including oxyHb, COHb, and metHb A, whereas the ligated Hbs exhibited similar UVRR spectra irrespective of the ligand species and the oxidation state of the heme. To characterize the spectral change of Trp-beta 37 at the alpha 1 beta 2 interface due to the quaternary structure transition, the UVRR spectra of Hb A were compared with the corresponding spectra of Hb Hirose (Trp-beta 37-->Ser). A difference spectrum between deoxyHb A and deoxyHb Hirose showed only Trp resonance Raman (RR) bands, which were reasonably ascribed to Trp-beta 37 in deoxyHb A. RR bands at 873 cm-1 (W17) and at 1360 and 1343 cm-1 (W7, Fermi doublet) indicated that the indole ring of Trp-beta 37 in deoxyHb A formed a strong hydrogen bond at the N1H site in hydrophobic environments. Tyr residues in deoxyHb Hirose seemed to be in the same environments as those of deoxyHb A. In contrast, the difference spectrum between Hb A and Hb Hirose in the ligated state displayed peaks for RR bands of both Trp and Tyr. The difference spectra were unaltered by the addition of 5 mM inositol hexaphosphate. This means that the differences were not caused by the tetramer to dimer dissociation but by a conformation change within a tetramer. Comparison of the Hb A-Hb Hirose difference spectra in the oxy and deoxy states revealed that the oxygenation-induced changes of Trp RR bands arose mostly from Trp-beta 37 with the small portion of remaining changes coming from Trp-beta 15, demonstrating that Trp-beta 37 plays a pivotal role in the quaternary structural change in Hb A. | {
"pile_set_name": "PubMed Abstracts"
} |
[Virus-specific structures in Sendai virus infected Ehrlich ascitic carcinoma cells].
A virus-specific structure representing a ribonucleoprotein (RNP) associated with cell membranes was found in the cytoplasm of Sendai virus-infected cells of Ehrlich ascitic carcinoma. RNP could be separated from the membranes by recentrifugation of this structure in cesium chloride density gradient. In the liquid fraction, a structure with the same buoyant density possessing infectious activity was found. All structural polypeptides of virions with the exception of the membrane protein are found in the composition of the intracellular and extracellular structures. | {
"pile_set_name": "PubMed Abstracts"
} |
Dietary restriction modifies certain aspects of the postoperative acute phase response.
Lifespan extension is achieved through long-term application of dietary restriction (DR), and benefits of short-term dietary restriction on acute stress and inflammation have been observed. So far, the effects of short-term DR in humans are relatively unknown. We hypothesized that short-term DR in humans reduces the acute phase response following a well defined surgical trauma. Thirty live kidney donors were randomized between 30% preoperative dietary restriction followed by 1 d of fasting (n=17) or a 4 d ad libitum regimen (n=13) prior to surgery. Leukocyte subsets and numbers and serum cytokine levels were determined. Whole blood was stimulated with lipopolysaccharide (LPS) and cytokine production was determined. A clear trend towards lower numbers of postoperative circulating leukocytes was observed in the DR group. IL-8 serum levels were significantly higher in the DR group over the first 6 postoperative d (P=0.018). After LPS stimulation, significantly less TNF-α (P=0.001) was produced by blood obtained postoperatively compared with preoperative blood from the DR group. This was not observed in the control group. A relatively short preoperative dietary restriction regimen was able to modify certain aspects of the postoperative acute phase response. These data warrant further studies into the dietary conditions that improve stress resistance in humans. (Dutch Trial Registry number: NTR1875). | {
"pile_set_name": "PubMed Abstracts"
} |
DNA binding factors that bind to the negative regulatory element of the human immunodeficiency virus-1: regulation by nef.
The nef gene has been reported to be a silencer of human immunodeficiency virus (HIV) transcription that requires the presence of the negative regulatory element (NRE) located at the 5' end of the HIV long terminal repeat (LTR) to exert its negative effect. We have examined nuclear extracts from human, nontransformed T cells for factors that bind to the NRE of HIV-1 and to determine whether binding of factors to this region can be affected by the nef gene. Using gel retardation and methylation interference assays, we have observed several DNA binding factors that bind to a region between nucleotides -315 and -240 upstream of the cap site, within the NRE segment of the 5' LTR. Furthermore, the precise locations of the binding sites for two of these factors, termed here A1 and R, were determined. Factor A1 appears to belong to a family of cellular activation associated factors (called here A1-A4), but it is distinct in that it is the only DNA binding factor so far observed that appears to be downregulated by the nef gene or its product and that it has been found only in cells undergoing lymphokine-driven cell division. In contrast to the A factors, factor R appears to be associated with cellular quiescence and binds to a nearby but distinct site in the NRE. Experiments in which extracts were mixed before gel retardation suggest that the binding of factors R and A1 are mutually exclusive. Based on these observations we propose a model in which the nef gene aids in the maintenance of HIV latency by downregulating the binding of proliferation associated DNA binding factor, which we have called A1. | {
"pile_set_name": "PubMed Abstracts"
} |
Deciphering the role of Gi2 in opioid-induced adenylyl cyclase supersensitization.
Prolonged opioid treatment of HEK 293 cells expressing opioid receptors are known to induce adenylyl cyclase supersensitization, a process that requires pertussis toxin (PTX)-sensitive G(i/o) proteins. Here, the role of Gi2 in adenylyl cyclase supersensitization was investigated. A PTX-insensitive G alpha(i2)/z chimera was stably co-expressed with mu-, kappa- or delta-opioid receptors in HEK 293 cells. Functional coupling of G alpha(i2)/z to the opioid receptors was demonstrated by opioid-induced inhibition of adenylyl cyclase and stimulation of ERK1/2 phosphorylation in PTX-treated cells. Chronic opioid treatment of each cell line led to adenylyl cyclase supersensitization but this response was blocked by PTX. Our results demonstrated that although PTX-sensitive G proteins are obligatory for opioid-induced adenylyl cyclase supersensitization, Gi2 alone was insufficient to mediate this response. | {
"pile_set_name": "PubMed Abstracts"
} |
Financial factor influence on scaling and memory of trading volume in stock market.
We study the daily trading volume volatility of 17,197 stocks in the US stock markets during the period 1989-2008 and analyze the time return intervals τ between volume volatilities above a given threshold q. For different thresholds q, the probability density function P(q)(τ) scales with mean interval 〈τ〉 as P(q)(τ)=〈τ〉(-1)f(τ/〈τ〉), and the tails of the scaling function can be well approximated by a power law f(x)∼x(-γ). We also study the relation between the form of the distribution function P(q)(τ) and several financial factors: stock lifetime, market capitalization, volume, and trading value. We find a systematic tendency of P(q)(τ) associated with these factors, suggesting a multiscaling feature in the volume return intervals. We analyze the conditional probability P(q)(τ|τ(0)) for τ following a certain interval τ(0), and find that P(q)(τ|τ(0)) depends on τ(0) such that immediately following a short (long) return interval a second short (long) return interval tends to occur. We also find indications that there is a long-term correlation in the daily volume volatility. We compare our results to those found earlier for price volatility. | {
"pile_set_name": "PubMed Abstracts"
} |
The 1.1 A crystal structure of human TGF-beta type II receptor ligand binding domain.
Transforming growth factor beta (TGF-beta) is involved in a wide range of biological functions including development, carcinogenesis, and immune regulation. Here we report the 1.1 A resolution crystal structure of human TGF-beta type II receptor ectodomain (TBRII). The overall structure of TBRII is similar to that of activin type II receptor ectodomain (ActRII) and bone morphogenic protein receptor type IA (BRIA). It displays a three-finger toxin fold with fingers formed by the beta strand pairs beta1-beta2, beta3-beta4, and beta5-beta6. The first finger in the TBRII is significantly longer than in ActRII and BRIA and folds tightly between the second finger and the C terminus. Surface charge distributions and hydrophobic patches predict potential TBRII binding sites. | {
"pile_set_name": "PubMed Abstracts"
} |
Modified potential for atomistic simulation of the growth of carbon materials from binary alloy catalysts.
A new hybrid bond order potential has been developed and implemented to describe carbon-bimetallic alloy interactions, which are involved in the catalytic growth of carbon materials such as graphene and carbon nanotubes on the surface of binary alloy catalysts. In carefully adjusting the parameters, the potential energy fitting correlated with the results calculated from the density functional theory (DFT) method leads to a high quality empirical force field with an average error of <4.5% only. With the PES accuracy, in total 16 (n,m) have been successfully obtained from the MD trajectories in this work, and the structural evolution including random chirality and diameter formation has been identified. The newly modified force field is expected to be useful for modelling the spontaneous growth of carbon materials, particularly tubes on binary alloy clusters, giving an idea of how these C-C, C-M, and M-M interactions affect the growth behavior of carbon nanotubes. In addition, the new FF is only valid for liquid alloy nanoparticles at this time, but the use of solid alloy nanocatalysts with the new FF can be further employed for 2-D material growth such as graphene layer growth. | {
"pile_set_name": "PubMed Abstracts"
} |
High-throughput evaluation of quiescent hematopoietic progenitor cells using a micro-multiwell plate.
Conventional assays for hematopoietic progenitor cells (HPCs) require long-term culturing, a labor-intensive procedure, and technique proficiency. We aimed to develop a high-throughput method to determine frequency of quiescent primitive HPCs by a combination of the micro-multiwell plate and 5-fluorouracil (5-FU) treatment. The micro-multiwell plate was made of a silicone sheet with a 6 x 6 array of 1-mm diameter holes and a glass substrate. To enrich primitive HPCs in a CD34 population, CD34 cells and stromal cells were applied to micro-multiwells and cultured in the presence of 5-FU for 2 days. The quiescent primitive HPCs that survived after 5-FU treatment were then expanded with cytokines in the absence of 5-FU for a further 10 days. After culturing, cells were immunostained and the number of primitive HPCs in inoculated CD34 cells was estimated from fluorescent intensity for each well under a stereoscopic fluorescent microscope. The frequencies of primitive HPCs correlated well with frequencies of cobblestone area-forming cells for two CD34 cell lots. Our method allows high-throughput screening for primitive HPCs in CD34 cells. | {
"pile_set_name": "PubMed Abstracts"
} |
On the presence of lysozyme in the Nuclei of Leukocytes.
The purified chromatin of leukocyte nuclei from two patients, one with chronic granulocytic and another with acute myelomonocytic leukemia, has been investigated for lysozyme activity. The chromatin contained 4.8% resp. 4% of the total amount of lysozyme found in the leukocytes. The function of lysozyme in the nucleus remains unclear. | {
"pile_set_name": "PubMed Abstracts"
} |
Shrapnel splinter in the common bile duct.
Obstructive jaundice is infrequently caused by a foreign body. We report a 42-year-old man who presented with obstructive jaundice by an impacted shrapnel splinter in the common bile duct (CBD) 23 years after a combat injury. To our knowledge, this is the first case report of this type in Iranian literature, although there are a few reports of combat related injuries in other countries. This diagnosis should be considered in the assessment of any patient with jaundice and abdominal pain who has experienced a previous combat injury. | {
"pile_set_name": "PubMed Abstracts"
} |
Bent Knee Temporary Prosthesis to Support Early Ambulation after Transtibial Amputation: A Case Report.
Postoperative immobility can exacerbate the physical and psychologic effects of limb loss. This case report presents a 37-year-old mother of two children who required a transtibial amputation. She received an early ambulation device called the bent knee temporary prosthesis (BKTP), which aids in early postoperative ambulation. Several early ambulation devices have been utilized in the past but have not found widespread favor. Although there is a paucity of research on this topic, available data suggest patient tolerance and benefit of early ambulation. A customizable, temporary below knee prosthesis such as the BKTP is valuable to study the safety and efficacy of early postoperative ambulation for improving outcomes for transtibial amputees. | {
"pile_set_name": "PubMed Abstracts"
} |
Screening for borderline personality disorder in outpatient youth.
Young people with borderline personality disorder (BPD) commonly seek help but often go unrecognized. Screening offers a means of identifying individuals for more detailed assessment for early intervention and for research. This study compared the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD), Borderline Personality Questionnaire (BPQ), the BPD items from the International Personality Disorder Examination Screening Questionnaire and the BPD items from the Structured Clinical Interview for DSM-IV Axis II disorders (SCID-II) Personality Questionnaire. 101 outpatient youth (aged 15-25 years) completed the screening measures and were interviewed, blind to screening status, with the SCID-II BPD module. The screening measures were readministered two weeks later to assess test-retest reliability. All four instruments performed similarly but the BPQ had the best mix of characteristics, with moderate sensitivity (0.68), the highest specificity (0.90), high negative predictive value (0.91) and moderate positive predictive value (0.65). Compared to the other three instruments, the BPQ had the highest overall diagnostic accuracy (0.85), a substantially higher kappa (0.57) with the criterion diagnosis, the highest test-retest reliability (ICC = 0.92) and the highest internal consistency (alpha = 0.92). The only clear difference to emerge in the Receiver Operator Curve (ROC) analysis was that the BPQ significantly outperformed the MSI (p = 0.05). Screening for BPD in out-patient youth is feasible but is not a replacement for clinical diagnosis. | {
"pile_set_name": "PubMed Abstracts"
} |
Unequal crossover dynamics in discrete and continuous time.
We analyze a class of models for unequal crossover (UC) of sequences containing sections with repeated units that may differ in length. In these, the probability of an 'imperfect' alignment, in which the shorter sequence has d units without a partner in the longer one, scales like qd as compared to 'perfect' alignments where all these copies are paired. The class is parameterized by this penalty factor q. An effectively infinite population size and thus deterministic dynamics is assumed. For the extreme cases q = 0 and q = 1, and any initial distribution whose moments satisfy certain conditions, we prove the convergence to one of the known fixed points, uniquely determined by the mean copy number, in both discrete and continuous time. For the intermediate parameter values, the existence of fixed points is shown. | {
"pile_set_name": "PubMed Abstracts"
} |
Korean American health insurance and health services utilization.
The purpose of this ethnic group study was to describe the unique pattern of Korean Americans, as compared with the aggregate of Asian Americans, for: (a) the predisposing, enabling, and need factors for health service utilization, focusing specifically on the role of health insurance coverage; and (b) predictors of health insurance coverage. Using the behavioral model for health service utilization, data were selected from the 1992 National Health Insurance Survey (NHIS, 1994) for Korean Americans (n = 345) and Asian Americans (n = 3,059). Results differed between the Korean American group and the Asian American group. Health insurance coverage was the strongest predictor of Korean American utilization, and need factors lacked significance, suggesting that uninsured Korean Americans have less access regardless of need. For the aggregate Asian American group, need factors tempered the influence of health insurance on utilization. Results of this type of study may be helpful for designing and implementing health care services tailored for specific ethnic at-risk markets. | {
"pile_set_name": "PubMed Abstracts"
} |
The International Liaison Committee on Resuscitation (ILCOR) consensus on science with treatment recommendations for pediatric and neonatal patients: pediatric basic and advanced life support.
This publication contains the pediatric and neonatal sections of the 2005 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (COSTR). The consensus process that produced this document was sponsored by the International Liaison Committee on Resuscitation (ILCOR). ILCOR was formed in 1993 and consists of representatives of resuscitation councils from all over the world. Its mission is to identify and review international science and knowledge relevant to cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC) and to generate consensus on treatment recommendations. ECC includes all responses necessary to treat life-threatening cardiovascular and respiratory events. The COSTR document presents international consensus statements on the science of resuscitation. ILCOR member organizations are each publishing resuscitation guidelines that are consistent with the science in this consensus document, but they also take into consideration geographic, economic, and system differences in practice and the regional availability of medical devices and drugs. The American Heart Association (AHA) pediatric and the American Academy of Pediatrics/AHA neonatal sections of the resuscitation guidelines are reprinted in this issue of Pediatrics (see pages e978-e988). The 2005 evidence evaluation process began shortly after publication of the 2000 International Guidelines for CPR and ECC. The process included topic identification, expert topic review, discussion and debate at 6 international meetings, further review, and debate within ILCOR member organizations and ultimate approval by the member organizations, an Editorial Board, and peer reviewers. The complete COSTR document was published simultaneously in Circulation (International Liaison Committee on Resuscitation. 2005 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation. 2005;112(suppl):73-90) and Resuscitation (International Liaison Committee on Resuscitation. 2005 International Consensus Conference on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Resuscitation. 2005;67:271-291). Readers are encouraged to review the 2005 COSTR document in its entirety. It can be accessed through the CPR and ECC link at the AHA Web site: www.americanheart.org. The complete publication represents the largest evaluation of resuscitation literature ever published and contains electronic links to more detailed information about the international collaborative process. To organize the evidence evaluation, ILCOR representatives established 6 task forces: basic life support, advanced life support, acute coronary syndromes, pediatric life support, neonatal life support, and an interdisciplinary task force to consider overlapping topics such as educational issues. The AHA established additional task forces on stroke and, in collaboration with the American Red Cross, a task force on first aid. Each task force identified topics requiring evaluation and appointed international experts to review them. A detailed worksheet template was created to help the experts document their literature review, evaluate studies, determine levels of evidence, develop treatment recommendations, and disclose conflicts of interest. Two evidence evaluation experts reviewed all worksheets and assisted the worksheet reviewers to ensure that the worksheets met a consistently high standard. A total of 281 experts completed 403 worksheets on 275 topics, reviewing more than 22000 published studies. In December 2004 the evidence review and summary portions of the evidence evaluation worksheets, with worksheet author conflict of interest statements, were posted on the Internet at www.C2005.org, where readers can continue to access them. Journal advertisements and e-mails invited public comment. Two hundred forty-nine worksheet authors (141 from the United States and 108 from 17 other countries) and additional invited experts and reviewers attended the 2005 International Consensus Conference for presentation, discussion, and debate of the evidence. All 380 participants at the conference received electronic copies of the worksheets. Internet access was available to all conference participants during the conference to facilitate real-time verification of the literature. Expert reviewers presented topics in plenary, concurrent, and poster conference sessions with strict adherence to a novel and rigorous conflict of interest process. Presenters and participants then debated the evidence, conclusions, and draft summary statements. Wording of science statements and treatment recommendations was refined after further review by ILCOR member organizations and the international editorial board. This format ensured that the final document represented a truly international consensus process. The COSTR manuscript was ultimately approved by all ILCOR member organizations and by an international editorial board. The AHA Science Advisory and Coordinating Committee and the editor of Circulation obtained peer reviews of this document before it was accepted for publication. The most important changes in recommendations for pediatric resuscitation since the last ILCOR review in 2000 include: Increased emphasis on performing high quality CPR: "Push hard, push fast, minimize interruptions of chest compression; allow full chest recoil, and don't provide excessive ventilation" Recommended chest compression-ventilation ratio: For lone rescuers with victims of all ages: 30:2 For health care providers performing 2-rescuer CPR for infants and children: 15:2 (except 3:1 for neonates) Either a 2- or 1-hand technique is acceptable for chest compressions in children Use of 1 shock followed by immediate CPR is recommended for each defibrillation attempt, instead of 3 stacked shocks Biphasic shocks with an automated external defibrillator (AED) are acceptable for children 1 year of age. Attenuated shocks using child cables or activation of a key or switch are recommended in children <8 years old. Routine use of high-dose intravenous (IV) epinephrine is no longer recommended. Intravascular (IV and intraosseous) route of drug administration is preferred to the endotracheal route. Cuffed endotracheal tubes can be used in infants and children provided correct tube size and cuff inflation pressure are used. Exhaled CO2 detection is recommended for confirmation of endotracheal tube placement. Consider induced hypothermia for 12 to 24 hours in patients who remain comatose following resuscitation. Some of the most important changes in recommendations for neonatal resuscitation since the last ILCOR review in 2000 include less emphasis on using 100% oxygen when initiating resuscitation, de-emphasis of the need for routine intrapartum oropharyngeal and nasopharyngeal suctioning for infants born to mothers with meconium staining of amniotic fluid, proven value of occlusive wrapping of very low birth weight infants <28 weeks' gestation to reduce heat loss, preference for the IV versus the endotracheal route for epinephrine, and an increased emphasis on parental autonomy at the threshold of viability. The scientific evidence supporting these recommendations is summarized in the neonatal document (see pages e978-e988). | {
"pile_set_name": "PubMed Abstracts"
} |
PP037. Family history of cardiovascular disease and maternal vascular function during early pregnancy.
Women with a family history of cardiovascular disease (CVD) have an increased risk of hypertensive disorders during pregnancy. Pregnancy is associated with increased physical demands on the cardiovascular system and hemodynamic changes. Cardiac output increases by about 40-50%, blood volume by 10-20% and vascular resistance decreases. Our hypotheses was that women with a family history of CVD fail to have an adequate cardiovascular adaptation during pregnancy. Fifty healthy women with singleton viable pregnancies were included in the study who were recorded in the Ultrasound Department of UltraGyn Stockholm, Sweden for ultrasound dating in gestational week of 11-14. Of these, 25 women had a family history of CVD which was defined as having at least one first degree relative with the diagnosis of premature hypertension, myocardial infarct or stroke before the age of 55 (men) or 65 (women). Twenty five healthy women without a family history were included as controls. Smokers were excluded. Blood pressure was measured in the upper left arm in a conventional way. The pulse wave was registered in the radial artery (SphygmoCor Px and Vx, PWV Medical). The central blood pressure was calculated with a validated algorithm. The pulse wave was then registered in the femoral artery, the velocity was calculated and the arterial stiffness estimated. Flow mediated vasodilation was studied in the radial artery through measurement with ultrasound of diameter changes and blood flow before and after ischemia (Vivid 7, GE, 10MHz transducer). Systolic blood pressure in the upper left arm was significantly higher in women with a family history of CVD (median 109.5mmHg versus 105mmHg, p=0.04). Diastolic blood pressure did not differ. Aortic blood pressure also differed significantly in women with a family history of CVD, both systolic (median 95mmHg versus 86.3mmHg, p=0.0005) and diastolic (median 66mmHg versus 59.3mmHg, p=0.0024). No other results were significantly different. All values refer to examinations at gestational weeks 11-14. Changes in vascular function during the first trimester reflect important adaptations that are necessary for a normal pregnancy. Women with a family history of CVD had a significantly higher blood pressure at 11-14weeks of gestation although the values were within normal range. The pregnancy related decrease of vascular resistance may be less pronounced in women with a family history of CVD. Vascular function will be followed longitudinally during pregnancy and related to obstetric outcome in this group. | {
"pile_set_name": "PubMed Abstracts"
} |
Study of the antioxidant effect of several selenium and sulphur compounds.
Four selenium derivatives (sodium selenate, sodium selenite, selenourea and selenomethionine) and the sulphur analogues (sodium sulfate, sodium sulfite, thiourea and methionine), together with urea, were examined by means of polarography to study their reactivity towards superoxide ion O2. In order that experimental results could be applied to physiological conditions and to control the electroreduction of oxygen, most reactions were carried out in model systems (in the presence and in the absence of triphenyl phosphine oxide and at increasing pH) which are briefly described and discussed. Sodium sulfite and thiourea react with molecular oxygen; selenourea originates an anodic wave, although under other pH conditions. Other compounds (selenate, selenite, seleno-methionine and methionine) display an interesting antioxidant capacity because they catalyse the disproportion of the superoxide ion, as documented by the increase in the limiting current. Methionine appears to be particularly efficient in this respect, since it retains its catalytic ability in a poorly protic environment. Experimental results support the view that exogenous compounds, administered for particular purposes, can display unanticipated, and sometimes positive, side effects. | {
"pile_set_name": "PubMed Abstracts"
} |
Spectroscopic (FT-IR/FT-Raman) and computational (HF/DFT) investigation and HOMO/LUMO/MEP analysis on 2-amino-4-chlorophenol.
The spectra (FT-IR and FT-Raman) of the present compound; 2-amino-4-chlorophenol (2A4CP) were recorded in the range of 4000-100 cm(-1). All the computational calculations were made in the ground state using the HF and DFT (B3LYP and B3PW91) methods with 6-31++G(d,p) and 6-311++G(d,p) basis sets. From potential energy surface calculation, there are two conformers, Rot-1 and Rot-2 for this molecule. The computational results detected that Rot-1 form is the most stable conformer. Making use of the recorded data, the complete vibrational assignments were made and analysis of the observed fundamental bands of molecule is carried out. The complete assignments were performed on the basis of the total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanics (SQMs) method and PQS program. The shifting of the frequencies in the vibrational pattern of the title molecule due to the substitutions; NH(2) and Cl were deeply investigated by the vibrational analysis. Moreover, (13)C NMR and (1)H NMR chemical shifts were calculated by using the gauge independent atomic orbital (GIAO) method with HF/B3LYP/B3PW91 methods with 6-311++G(d,p). A study on the electronic properties, such as HOMO and LUMO energies, were performed by time-dependent DFT (TD-DFT) approach. Besides frontier molecular orbitals (FMOs), molecular electrostatic potential (MEP) was performed. NLO properties and Mulliken charges of the 2A4CP were also calculated and interpreted. The thermodynamic properties (heat capacity, entropy, and enthalpy) of the title compound at different temperatures were calculated in gas phase. | {
"pile_set_name": "PubMed Abstracts"
} |
Endoscopic treatment of biliary tract fistulas.
Endoscopic therapy was attempted in 24 patients with spontaneous or postoperative persistent biliary fistulas. Endoscopic retrograde cholangiography demonstrated the site of the fistula in 22 cases. Sphincterotomy or biliary stent placement resulted in rapid resolution of the fistula in 16 of 24 patients. Failures were attributed to exclusion of the injured intrahepatic bile duct in two cases, insufficient dilation of a bile duct stricture in one, the large size of the bile duct defect in two, and associated lesions in three (cirrhosis, arterial trauma, subhepatic abscess). Endoscopic management of biliary fistulae requires: (1) visualization of the location of the fistula by retrograde cholangiography especially in case of an intrahepatic lesion, (2) prior percutaneous drainage of associated subhepatic or subphrenic abscesses, and (3) appropriate relief of distal biliary obstruction in order to reduce the intraductal biliary pressure. The outcome is uncertain when endoprostheses are used to bridge large bile duct defects. | {
"pile_set_name": "PubMed Abstracts"
} |
Acute effects of ethanol and ethanol plus furosemide on pancreatic capillary blood flow in rats.
The effects of intravenous ethanol and ethanol plus furosemide on pancreatic capillary blood flow (PCBF) were investigated using a laser-Doppler flowmeter. Forty Sprague-Dawley male rats were divided into 4 groups: (1) control, (2) 80% ethanol, (3) 80% ethanol plus furosemide, and (4) furosemide. Mean arterial blood pressure and heart rate were monitored. Levels of serum amylase, calcium, electrolytes, ethanol, and furosemide (groups 3 and 4) were measured, and samples of pancreatic tissue were obtained. The ethanol and furosemide levels were statistically different (p < 0.05). PCBF significantly decreased (p < 0.05) in group 2, increased (p < 0.05) in group 3, and did not differ (p > 0.05) between groups 1 and 4. Histopathologic analysis revealed swollen acini in group 2 and sparse focal necrosis without acinar swelling in group 3. The depressant effect of ethanol on PCBF may be the result of its direct action on pancreatic cells causing edema and capillary compression rather than on primary vascular control mechanisms that adjust blood flow. Furosemide counters this effect. | {
"pile_set_name": "PubMed Abstracts"
} |
The echotextural characteristics for the diagnosis of the liver cirrhosis using the sonographic images.
Various statistical parameters have been tried for the computer-aided diagnosis of the liver fibrosis. The region of interest (ROI) for the liver and spleen parenchymas have been chosen, and the hepatolienal textural contrast for each ultrasound (US) image has been examined. The selectively chosen textural parameters are linearly combined with the pre-determined coefficients to give the computer-aided diagnostic parameter for the liver fibrosis, whose final stage is named as cirrhosis. From the comparison with the clinical diagnosis it is suggested that the proposed calculation scheme using the textural parameters show the quite promising classification performance for the computer-aided diagnosis of the liver cirrhosis. | {
"pile_set_name": "PubMed Abstracts"
} |
Evidence from beta-tubulin phylogeny that microsporidia evolved from within the fungi.
Microsporidia are obligate intracellular parasites that were thought to be an ancient eukaryotic lineage based on molecular phylogenies using ribosomal RNA and translation elongation factors. However, this ancient origin of microsporidia has been contested recently, as several other molecular phylogenies suggest that microsporidia are closely related to fungi. Most of the protein trees that place microsporidia with fungi are not well sampled, however, and it is impossible to resolve whether microsporidia evolved from a fungus or from a protistan relative of fungi. We have sequenced beta-tubulins from 3 microsporidia, 4 chytrid fungi, and 12 zygomycete fungi, expanding the representation of beta-tubulin to include all four fungal divisions and a wide diversity of microsporidia. In phylogenetic trees including these new sequences, the overall topology of the fungal beta-tubulins generally matched the expected relationships among the four fungal divisions, although the zygomycetes were polyphyletic in some analyses. The microsporidia consistently fell within this fungal diversification, and not as a sister group to fungi. Overall, beta-tubulin phylogeny suggests that microsporidia evolved from a fungus sometime after the divergence of chytrids. We also found that chytrid alpha- and beta-tubulins are much less divergent than are tubulins from other fungi or microsporidia. In trees in which the only fungal representatives were the chytrids, microsporidia still branched with fungi (i.e., with chytrids), suggesting that the affiliation between microsporidian and fungal tubulins is not an artifact of long-branch attraction. | {
"pile_set_name": "PubMed Abstracts"
} |
Health related quality of life in individuals with asthma related symptoms.
Where evidence is required for disease-area prioritisation (e.g. by national policymakers), impact on health related quality of life (HRQoL) can be considered equitably across diseases using quantitative data from generic HRQoL instruments. Before this can take place, it must be shown that the instrument captures HRQoL impairment associated with each disease area. To ascertain whether the HRQoL impairment associated with respiratory disease can be represented by responses to EQ-5D, a generic HRQoL questionnaire. EQ-5D and a respiratory health questionnaire were sent to 10,471 adults registered with two general practices in Manchester, UK. EQ-5D examines 5 domains (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and includes an overall rating via visual analogue scale. Societal valuations of domain responses were also considered. HRQoL was substantially reduced in respondents who were likely to have obstructive airways disease (mean EQ-5D(index) 0.63 compared to 0.82, t-test P < 0.001; mean EQ-5D(vas) 62.7 compared to 77.6, t-test P < 0.001) and was negatively associated with respiratory symptoms, older age and female gender. The association with respiratory problems remained following stratification by age and gender. The deficit in HRQoL associated with increasing age was more pronounced in those likely to have obstructive airways disease. HRQoL measured using EQ-5D is substantially reduced in respondents with respiratory symptoms enabling use of the instrument in inter-disease comparisons. | {
"pile_set_name": "PubMed Abstracts"
} |
CTLA-41g in combination with anti-CD40L prolongs xenograft survival and inhibits anti-gal ab production in GT-Ko mice.
The generation of GT-Ko mice has provided unique opportunities to study allograft and xenograft rejection in the context of anti-alpha1,3-Gal antibody (anti-Gal Ab) responses. In this study we used the allotransplantation model of C3H hearts into galactosyltransferase-deficient (GT-Ko) mice and the xenotransplantation model of baby Lewis rat hearts into GT-Ko mice to investigate the ability of CTLA-41g in combination with anti-CD40L mAb to control graft rejection and anti-Gal Ab production. Murine CTLA-41g or anti-CD40L monotherapy prolonged allograft survival, and the combination of these reagents was most immunosuppressive. However short-term treatment with murine cytotoxic T lymphocyte associated antigen-4 (muCTLA-41g) and/or CD40 ligand (CD154) monoclonal antibodies (anti-CD40L mAbs) was unable to induce indefinite allograft survival. CTLA-4-immunoglobulin fusion protein (CTLA-41g) or anti-CD40L monotherapy only marginally prolonged xenograft survival; the combination of human CTLA-41g and anti-CD40L significantly prolonged xenograft survival (74days), while the combination of murine CTLA-41g and anti-CD40L resulted in graft survival of >120days. CTLA-41g or anti-CD40L monotherapy or the combination of these agents inhibited the production of alloAbs, including anti-Gal Abs. CTLA-41g or anti-CD40L monotherapy partially controlled xenoAb and anti-Gal Ab production, while the combination was more effective. These observations corroborate our previous observations that humoral, including anti-Gal Ab, responses and rejection following allograft or concordant xenograft transplantation in GT-Ko mice are T-cell dependent and can be controlled by costimulation blockade. | {
"pile_set_name": "PubMed Abstracts"
} |
C-cell disease of the thyroid gland in multiple endocrine neoplasia, type 2b.
Multiple endocrine neoplasia, type 2b (MEN 2b) is a disorder characterized by C-cell disease of the thyroid gland (medullary carcinoma or C-cell hyperplasia, or both), pheochromocytoma, ganglioneuromatosis, and skeletal and connective tissue abnormalities. The medullary thyroid carcinoma (MTC) is bilateral and multicentric; it metastasizes locally and distally, often before the disease is recognized. Histologically proven C-cell disease was present in 89 of the 107 patients (83%) reported with the condition, including 17 Mayo Clinic patients (average age at diagnosis, 19.2 years). Nineteen of the 107 patients (18%) died of MTC (average age at death, 25.3 years); 9 (8%) succumbed to pheochromocytoma, 7 of these also having metastatic MTC; 13 12%) died of other or unknown causes, but 2 of these had disseminated MTC as well; 29 (27%) survive with metastatic MTC; an additional 21 (20%) are alive, but concentrations of plasma immunoreactive calcitonin (iCT) have not been measured; 6 more (6%), 5 of whom had thyroidectomy before the age of 12 years, are alive with normal plasma concentrations of iCT; and the remaining 10 (9%) have been lost to follow-up. Survival of patients with MEN 2b after operation was reduced when compared with that of a control population -- 80% versus 99% at 5 years and 50% versus 98% at 10 years. The only effective treatment for MTC is total thyroidectomy before metastasis occurs. "Cure" of MTC in patients with MEN 2b has generally been obtained in those having total thyroidectomy before age 12. Therefore, in young patients suspected of having MEN 2b, we recommend prompt evaluation of C-cell function by measurement of stimulated concentrations of iCT and treatment by total thyroidectomy if results are abnormal. | {
"pile_set_name": "PubMed Abstracts"
} |
The Effect of Gabapentin and Tramadol in Cancer Pain Induced by Glioma Cell in Rat Femur.
Preclinical Research The presence of pain as part of the cancer process is variable. Glioblastoma multiform (GBM) can produce bone metastasis, a condition that involves other pathological phenotypes including neuropathic and inflammatory pain. Tramadol and gabapentin are drugs used in the treatment of neuropathic pain. However, there are no studies evaluating their analgesic effects in bone metastasis. We produced a pain model induced by the inoculation of glioma cells (105 ) into the rat femur, by perforating the intercodiloid fossa. Painful behavior was evaluated by measuring mechanical allodynia using the Von Frey test while thermal hyperalgesia was assessed in the plantar test. Histopathological features were evaluated and antinociceptive responses were compared using tramadol and gabapentin. The inoculation of cells inside the right femur produced nociceptive behaviors. Tramadol and gabapentin produced an anti-allodynic effect in this condition, but tramadol did not produce an anti-hyperalgesic response. The development of this model will allow us to perform tests to elucidate the pathology of bone metastasis, cancer pain, and in particular the pain produced by glioma. Drug Dev Res 78 : 173-183, 2017. © 2017 Wiley Periodicals, Inc. | {
"pile_set_name": "PubMed Abstracts"
} |
Dieulafoy's lesion of the esophagus correctly diagnosed and successfully treated by the endoscopic injection of N-butyl-2-cyanoacrylate.
Dieulafoy's lesion is an arterial malformation in the subumucosal layer of the gastrointestinal tract that can cause massive bleeding. The esophagus is not a common location for this lesion. We present here a first report of Dieulafoy's lesion of the esophagus correctly diagnosed and successfully treated by the endoscopic injection of N-butyl-2-cyanoacrylate. | {
"pile_set_name": "PubMed Abstracts"
} |
Molecular Tumor Boards: current practice and future needs.
Due to rapid technical advances, steeply declining sequencing costs, and the ever-increasing number of targeted therapies, it can be expected that extensive tumor sequencing such as whole-exome and whole-genome sequencing will soon be applied in standard care. Clinicians will thus be confronted with increasingly complex genetic information and multiple test-platforms to choose from. General medical training, meanwhile, can hardly keep up with the pace of innovation. Consequently, there is a rapidly growing gap between clinical knowledge and genetic potential in cancer care. Multidisciplinary Molecular Tumor Boards (MTBs) have been suggested as a means to address this disparity, but shared experiences are scarce in literature and no quality requirements or guidelines have been published to date. Based on literature review, a survey among hospitals in The Netherlands, and our own experience with the establishment of a nationally operating MTB, this article evaluates current knowledge and unmet needs and lays out a strategy for successful MTB implementation. Having access to an MTB can improve and increase the application of genetics-guided cancer care. In our survey, however, <50% of hospitals and only 5% of nonacademic hospitals had access to an MTB. In addition, current MTBs vary widely in terms of composition, tasks, tools, and workflow. This may not only lead to variation in quality of care but also hinders data sharing and thus creation of an effective learning community. This article acknowledges a leading role for MTBs to govern (extensive) tumor sequencing into daily practice and proposes three basic necessities for successful MTB implementation: (i) global harmonization in cancer sequencing practices and procedures, (ii) minimal member and operational requirements, and (iii) an appropriate unsolicited findings policy. Meeting these prerequisites would not only optimize MTB functioning but also improve general interpretation and application of genomics-guided cancer care. | {
"pile_set_name": "PubMed Abstracts"
} |
[Influence of zafirlukast on pulmonary functions and quality of life in patients with asthma].
To explore the influence of zafirlukast on pulmonary functions and quality of life (QOL) in patients with mild-to-moderate asthma at the stage of attack and at the stable stage. Patients at the stage of attack were randomly divided into two groups: Group one is zafirlukast 20 mg twice daily plus inhaled the half quantity of glucocorticoid(budelade) of the Global Initiative for Asthma (GINA) standard quantity, long-effection aminophyllin 0.2 g twice daily and inhaled salbutamol when necessary; Group two: inhaled budelade of GINA standard quantity, long-effection aminophyllin 0.2 g twice daily and inhaled salbutamol when necessary). Patients' peak expiratory flow (PEF)/PEF predicted value % and delta PEFR% were determined at the second week and the forth week before and after the treatment. On the standard treatment, patients with the stable stage were added zafirlukast 20 mg twice a day. PEF values in the morning and evening and QOL were evaluated. After treating with zafirlukast, the PEF/PEF predicted value % and delta PEFR% in Group one were higher and lower than those of Group two respevtively. These changes were appeared in two days and were peaked in two weeks and the peak had been gone on for more than 4 weeks, but these were no significant difference between the Groups (P > 0.05); PEF values in the morning and evening in patients with the stable asthma increased 5.9% and 4.6% respectively and their QOL were improved in asthma symptoms, limitative activities, avoiding stimuli, and reacting on stimuli. Zafirlukast can improve pulmonary function, reduce the inhalation quantity of steroid in patients with mild-to-moderate asthma, and play an important role in treating and improving QOL in patients with the stable asthma. | {
"pile_set_name": "PubMed Abstracts"
} |
Prepregnancy weight status and the risk of adverse pregnancy outcome.
To examine the association between maternal pre-pregnancy weight status and the risk of stillbirth, pre-eclampsia and preterm delivery. Hospital-based cohort study using prospectively recorded data. Ten public hospitals in Buenos Aires, Argentina. 46,964 pregnant women who had a delivery during 2003-2006. Prepregnancy body mass index (BMI) was used to categorize women in four weight categories from underweight to obese. The reference group were women with BMI between 18.5 and 24.9. Crude and adjusted odds ratios were calculated using multiple logistic regression analysis. Preterm birth, pre-eclampsia and stillbirth. The risk of preterm delivery decreased with increasing BMI, with the highest risk among underweight women (OR: 1.45; 95% CI: 1.26-1.67), and the lowest risk among the overweight. The risk of pre-eclampsia was highest among overweight (OR: 1.55; 95%CI: 1.30-1.86) and obese women (OR: 3.10; 95%CI: 2.54-3.78). Obese or overweight women did not have an increased risk of stillbirth in this study. Overweight and obese women have an increased risk for pre-eclampsia, while underweight women have an increased risk for preterm delivery. There is a high prevalence of overweight women in the obstetric population in Buenos Aires. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of microbubbles on ultrasound-mediated gene transfer in human prostate cancer PC3 cells: comparison among Levovist, YM454, and MRX-815H.
We compared the enhancement effects of three different echo contrast agents (ECAs); Levovist, YM454, and MRX-815H as artificial microbubbles on ultrasound mediated gene transfection (USMGT) with 1MHz ultrasound at 0.2MPa using a luciferase expression vector in PC3 cells and elucidated the mechanisms of differences of USMGT facilitation by these ECAs. At a concentration of each ECA that induced iso-survival, ECAs with lipid shell (YM454 and MRX-815H) facilitated USMGT higher than those without shell (Levovist), and the order of the ECAs facilitating free radical formation by sonication was; YM454>MRX-815H>Levovist. These results suggested that the lipid shell type ECAs facilitated gene transfer higher than that by the non-shell type ECA. | {
"pile_set_name": "PubMed Abstracts"
} |
The N-nitrosoproline test as a measure of cancer risk in geographical comparison studies: results from Italy and an overall comparison.
The N-nitrosoproline (NPRO) test has been used in studies in which populations at high risk of cancer have been compared with equivalent populations at lower risk, to examine whether the geographical variation in cancer risk correlates with propensity for endogenous nitrosation, as assessed by the NPRO test. The usual method employed has been to determine NPRO in 12- or 24-h urine samples, after ingestion of L-proline, in a representative sample of the general population. We present results from one such geographical study conducted in two regions of Italy (Florence and Cagliari) with an approximately three-fold variation in gastric cancer mortality. The nonsignificant difference in mean NPRO excretion between the two populations was insufficient to explain the difference in cancer risk. The fact that there are appreciable international differences in formation of NPRO suggests, firstly, that nitrosation may be of relevance to cancer risk in some countries but not in others and, secondly, that variations within one country may not be large enough for significant geographical differences to be evident. Multivariate analysis of individual, rather than grouped, results from our Italian study made it possible to quantify the relevance of different factors to NPRO formation: a major factor is exposure to nitrate. Important relationships may be missed by analysing only grouped data. | {
"pile_set_name": "PubMed Abstracts"
} |
Overcome toxic management.
Ineffective, ill-tempered managers hurt employee morale and productivity. Learn what behaviors characterize toxic managers, how they damage an organization, and how to lessen their impact. | {
"pile_set_name": "PubMed Abstracts"
} |
Transcript mapping of the human chromosome 11q12-q13.1 gene-rich region identifies several newly described conserved genes.
Despite the localization of several human diseases to 11q13, the majority of the genes responsible for these disorders have not yet been cloned. Exon amplification and EST mapping were performed using clones derived from an approximately 1.65-Mb P1 artificial chromosome contig encompassing the region that reportedly harbors the gene mutated in the dominantly inherited eye disorder, Best disease. Fifty-eight exons isolated from the region were sequenced, resulting in 41.3% showing weak or no similarity to database sequences. Four exons had exact matches with human ESTs and 2 exons were highly similar to mouse ESTs. The sequence of 1 of these human ESTs was highly similar to that of the rat Rabin3 and mouse Pat-12 genes, which potentially encode Ras-like GTPase binding proteins. Three exon sequences were similar to those of the inner centromere proteins of Gallus gallus and Xenopus laevis, which are mitotic phosphoproteins, and 1 exon sequence had similarity to the epidermal growth factor-like repeat from several proteins. High-resolution mapping of 34 ESTs binned to the 11q12-q13 region by the Human Transcript Mapping Project identified 5 present in the PAC contig, with 1 of these ESTs identifying a human homologue of the rat synaptotagmin VII gene. Database searches identified two overlapping cDNA clones representing almost the entire open reading frame of this human gene and a sequenced cosmid indicating its partial genomic structure. Further database analyses identified another sequenced cosmid from this region that contained both exon-trap and mapped EST sequences. PowerBLAST and GRAIL analysis of this cosmid sequence identified matches with several other ESTs, the previously described FEN1 gene, and a novel evolutionarily conserved gene. These experiments identify candidate genes for disorders that map to this region and indicate that this is a gene-rich region of the human genome. | {
"pile_set_name": "PubMed Abstracts"
} |
[Influence of adjustment of balance of Th1/Th2 type cytokines on proliferation of glioma cells].
To study the influence of adjustment of balance of Th1/Th2 by external cytokines on proliferation of glioma cells. The gene expressions of Th1/Th2 type cytokines in C6, 9L, U251 and SHG44 glioma cells were detected by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). After the cells were induced with IFN-gamma + IL-4 McAb and IL-4 + IFN-gamma McAb respectively, we isolated the total RNA to proceed RT-PCR again. The evaluation of cell proliferation was proceeded by MTT assay method. There was obviously predominant expression of Th2 type cytokines in glioma cell lines (P < 0.01). The expression intensity of IFN-gamma was improved in IFN-gamma + IL-4 McAb groups and Th2 type cytokines were enhanced in IL-4 + IFN-gamma McAb groups. IFN-gamma and IL-4 McAb could cause the switch from Th2 to Th1, and could remarkably inhibit the proliferation of glioma cells in a dose-dependent way (P < 0.01). On the other hand, IL-4 and IFN-gamma McAb could strengthen the switch of Th2, and might stimulate the glioma cell growth, also in a dose-dependent way (P < 0.01). There is a Th2 preponderance in glioma cells. IFN-gamma and IL-4 McAb could regulate the switch from Th2 to Th0 or Th1, and inhibit the proliferation of glioma cells. | {
"pile_set_name": "PubMed Abstracts"
} |
Communities, collectivities, and the ethics of research.
Ethical concerns have always placed limits on research, but the spirit of the times has led to an expansion of the territory covered by ethics. This new approach is found in the code of ethics presently in final revision by the three major granting agencies. This code will give unprecedented power to "collectivities" in the research process. Some see this as a long overdue corrective to hit-and-run research, while others see it as a threat to unfettered inquiry. This paper argues a different point: Involvement of collectivities is essential for ethical research relationships, but it ought not to limit the sorts of questions we study or publication of the answers we find. The difference will be illustrated by two examples in which aboriginal communities asserted their collective rights against researchers. The difference between the examples will lead to an examination of the debate between those who believe community work is "all politics," and those who try to underpin it with ethical principles. Finally, I argue that ethical practice requires a knowledge base created by valid research. We should support an improved relationship with host communities, but not let the political agendas of contending community groups constrain the questions we can ask about social problems or our assessment of measures designed to solve them. | {
"pile_set_name": "PubMed Abstracts"
} |
Hyposalivation: the roles of radioactive iodine and stapes surgery.
The aim of this study is to call attention to the role that radioactive iodine ((131)I) and stapes surgery may play in causing hyposalivation. The manner in which (131)I and stapes surgery can cause salivary damage was reviewed. A case report is presented to illustrate the involved pathophysiology. The case report clearly shows the significant injury to the parotid glands caused by the (131)I. However, subjective symptoms of oral dryness only developed after injury to the chorda tympani nerve (CTN) during stapes surgery. The loss of function of both parotid glands after (131)I therapy for thyroid cancer was initially compensated by the secretions of the more radiation-resistant submandibular and sublingual salivary glands (SMSG/SLSG). Damage to the CTN's secretory fibers in one SMSG/SLSG complex led to subjective oral dryness by accentuating an existing objective hyposalivation. | {
"pile_set_name": "PubMed Abstracts"
} |
Response characteristics of neurons in the ventral posterior lateral nucleus of the monkey thalamus.
The activity of 132 neurons in the caudal part of the ventral posterior lateral nucleus (VPLc) of the thalamus was recorded from 23 anesthetized monkeys. All single thalamic units that could be excited by electrical search stimuli applied to the contralateral sciatic nerve were investigated. Responses of these cells to mechanical, thermal, and electrical stimuli applied in the periphery indicated that at least half of the sampled cells were nociceptive. Based on responses to graded mechanical stimuli applied to the periphery, 110 of the sampled cells that received a predominant input from cutaneous receptive fields were classified. There were 56 low-threshold, 39 wide dynamic range, and 15 high-threshold cells. The same neurons were also classified into five mechanical types based on a cluster analysis: types 1-5 contained 25, 34, 17, 10, and 24 cells, respectively. The fact that about half the population of cells belonged to either the wide dynamic or the high threshold group (or mechanical types 3-5) suggested that a large population of VPLc neurons respond to mechanical nociceptive stimuli either exclusively or preferentially. Responses of 63 thalamic neurons were tested to noxious heat pulses applied to their cutaneous receptive fields with a contact thermostimulator. Of these, 47 cells were excited, whereas only 16 cells did not respond. The peripheral nerve that innervated the receptive field of each of 82 thalamic neurons was stimulated with graded strengths to activate A fibers only or both A and C fibers. All tested cells responded to peripheral A fiber volleys. In addition, 42 of these cells responded to peripheral C fiber volleys. The C fiber responses could be either short lasting (a few hundreds of milliseconds) or long lasting (up to several seconds). The recording sites of 80 cells were reconstructed. Of these, 78 were in the VPLc nucleus and the remaining two were in the reticular nucleus of the thalamus. No obvious relationship between the response characteristics and the locations of the cells within the VPLc nucleus was found. Sampled thalamic units had a variety of sources of input from the periphery, including both cutaneous and/or deep tissue receptive fields. The majority of the cells, however, had exclusively cutaneous receptive fields. The sizes of the cutaneous receptive fields were often very small, so that nearly half (41%) of the receptive fields of cells sampled occupied an area of skin smaller than half the foot.(ABSTRACT TRUNCATED AT 400 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
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