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Mitochondrial development in Trypanosoma brucei brucei transitional bloodstream forms. Intermediate and short stumpy bloodstream forms of Trypanosoma brucei brucei are transitional stages in the differentiation of mammal-infective long slender bloodstream forms into the procyclic forms found in the midgut of the tsetse vector. Although the mitochondria of the proliferative long slender forms do not accumulate rhodamine 123, the mitochondria of the transitional forms attain this ability thus revealing the development of an electromotive force (EMF) across the inner mitochondrial membrane. The EMF is inhibited by 2,4-dinitrophenol, rotenone and salicylhydroxamic acid but not by antimycin A or cyanide. Consequently, NADH dehydrogenase, site I of oxidative phosphorylation, is the source of the EMF and the plant-like trypanosome alternative oxidase (TAO) supports the electron flow serving as the terminal oxidase of the chain. Although the TAO is present in the long slender forms as well, it serves only as the terminal oxidase for electrons from glycerol-3-phosphate dehydrogenase. The data presented here, combined with older data, lead to the conclusion that the mitochondria of transitional intermediate and short stumpy forms likely produce ATP. This putative production is either by F1F0 ATPase driven by the complex I proton pump or by mitochondrial substrate level phosphorylation, or most likely by both. These conclusions contrast with the previously held dogma that all bloodstream form mitochondria are incapable of ATP production.
{ "pile_set_name": "PubMed Abstracts" }
Prognostic significance of p53 mutation in suboptimally resected advanced ovarian carcinoma treated with the combination chemotherapy of paclitaxel and carboplatin. The prognostic significance of p53 mutation, microsattelite instability and DNA mismatch protein hMLH1 expression in suboptimally resected advanced ovarian carcinoma treated with the combination chemotherapy of paclitaxel and carboplatin was evaluated. The overall combination chemotherapy response rate and the complete remission rate were significantly higher among patients with mutant p53 tumors than those with wild-type p53 tumors (35/42 (83%) vs. 32/58 (55%); P=0.003 and 18/42 (43%) vs. 16/58 (28%); P=0.03, respectively). This tendency apparently existed in non-serous carcinoma, but not in serous carcinoma. Univariate analysis showed that the risk of death due to disease and risk of progression was significantly lower among patients with p53 mutation (P=0.0357 and 0.0281, respectively). However, the presence of microsattelite instability or loss of hMLH1 expression was not associated with either the clinical response or prognosis. Determining p53 mutational status can be useful in predicting therapeutic response to drugs in ovarian carcinoma, especially in non-serous tumors.
{ "pile_set_name": "PubMed Abstracts" }
Acute exercise induced changes in rat skeletal muscle mRNAs and proteins regulating type IV collagen content. This experiment tested the hypothesis that running-induced damage to rat skeletal muscle causes changes in synthesis and degradation of basement membrane type IV collagen and to proteins regulating its degradation. Samples from soleus muscle and red and white parts of quadriceps femoris muscle (MQF) were collected 6 h or 1, 2, 4, or 7 days after downhill running. Increased muscle beta-glucuronidase activity indicated greater muscle damage in the red part of MQF than in the white part of MQF or soleus. In the red part of MQF, type IV collagen expression was upregulated at the pretranslational level and the protein concentration decreased, whereas matrix metalloproteinase-2 (MMP-2), a protein that degrades type IV collagen, and tissue inhibitor of metalloproteinase-2 (TIMP-2), a protein that inhibits degradation, were increased in parallel both at mRNA and protein levels. Type IV collagen mRNA level increased in the white part of MQF and soleus muscle. The protein concentration increased in the white part of MQF and was unchanged in soleus muscle. MMP-2 and TIMP-2 changed only slightly in the white part of MQF and soleus muscle. The changes seem to depend on the severity of myofiber injury and thus probably reflect reorganization of basement membrane compounds.
{ "pile_set_name": "PubMed Abstracts" }
Towards a more comprehensive concept for prebiotics. The essential role of the gut microbiota for health has generated tremendous interest in modulating its composition and metabolic function. One of these strategies is prebiotics, which typically refer to selectively fermented nondigestible food ingredients or substances that specifically support the growth and/or activity of health-promoting bacteria that colonize the gastrointestinal tract. In this Perspective, we argue that advances in our understanding of diet-microbiome-host interactions challenge important aspects of the current concept of prebiotics, and especially the requirement for effects to be 'selective' or 'specific'. We propose to revise this concept in an effort to shift the focus towards ecological and functional features of the microbiota more likely to be relevant for host physiology. This revision would provide a more rational basis for the identification of prebiotic compounds, and a framework by which the therapeutic potential of modulating the gut microbiota could be more fully materialized.
{ "pile_set_name": "PubMed Abstracts" }
Stroke subtypes and lesion sites in Akita, Japan. Stroke patients who underwent computed tomography (CT) were enrolled in a stroke registry in Akita, Japan, which comprised 7288 first-ever stroke cases during 1999 to 2001. Differences in age and sex were evaluated with respect to type-specific incidences and lesion sites. The incidence increased with age, except for subarachnoid hemorrhage (SAH) in men after age 40. The incidence of intracerebral hemorrhage (IH) and cerebral infarction (CI) was higher in men than in women, whereas that for SAH was lower. The mean age of putaminal hemorrhage was lower than that of thalamic hemorrhage, and the mean age of cortical infarction was higher than that of CI in perforator regions, the cerebellum, and the pons. In subjects age 70 years and older, the proportion of thalamic hemorrhage in IH was larger in women than in men; for those age 50 years and older, the proportion of cortical infarction in CI was larger in men than in women. The proportions of anterior communicating artery aneurysms in men and internal carotid artery aneurysms in women were largest in SAH for all age groups. In conclusion, thalamic hemorrhage was most common in elderly women and cortical infarction was most common in middle-aged and elderly men. The feature of SAH occurring at a higher incidence in women than in men, with a sexual difference in aneurysmal distribution, was also observed.
{ "pile_set_name": "PubMed Abstracts" }
Extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation: long-term survival. Primary graft dysfunction (PGD) after lung transplantation is a major cause of morbidity and mortality. Venovenous or venoarterial extracorporeal membrane oxygenation (ECMO) allows lung recovery; however, the optimal approach and impact on long-term survival are unknown. We analyzed outcomes after ECMO use for PGD after lung transplantation at a single center over a 15-year period and assessed long-term survival. From March 1991 to March 2006, 763 lung or heart-lung transplants were performed at our center. Fifty-eight patients (7.6%) required early (0 to 7 days after transplant) ECMO support for PGD. Venovenous or venoarterial ECMO was implemented (32 and 26 cases) depending on the patient's hemodynamic stability, surgeon's preference, and the era of transplantation. Mean duration of support was 5.5 days (range, 1 to 20). Mean follow-up was 4.5 years. Thirty-day and 1- and 5-year survivals were 56%, 40%, and 25%, respectively, for the entire group. Thirty-nine patients were weaned from ECMO, 21 venovenous and 18 venoarterial (53.8% and 46.2%), with 1- and 5-year survivals of 59% and 33%, inferior to recipients not requiring ECMO (p = 0.05). Survival at 30 days and at 1 and 5 years was similar for the patients supported with venoarterial or venovenous ECMO (58% versus 55%, p = 0.7; 42% versus 39%, p = 0.8; 29% versus 22%, p = 0.6). Extracorporeal membrane oxygenation can provide acceptable support for PGD irrespective of the method used. Long-term survival of patients with primary graft dysfunction requiring ECMO (overall and weaned) was inferior to that of patients who did not require ECMO.
{ "pile_set_name": "PubMed Abstracts" }
The effect of apramycin on colonization of pathogenic Escherichia coli in the intestinal tract of chicks. The purpose of the present study was to examine the effect of apramycin sulphate on the colonization of pathogenic E. coli in the intestines of chicks. Apramycin treatment (0.5g/l in the drinking water) of 3-to 5-week-old Leghorn chicks for 24 or 48 hours resulted in a reduction, to an undetectable level, in the number of coliforms in the digestive tract for at least the first 24 h. Per os inoculation of E. coli (O2:K1) after 24 to 48 h of treatment resulted in a significant decrease in colony forming units (cfu) in the digestive tract of the treated chicks. Food deprivation from the time of inoculation did not significantly change the results. However, food and water deprivation caused bacteraemia in a number of the control chicks but not in the treated chicks. Comparison of the level of protection between Leghorn and broiler (Anak strain) chicks revealed that there was a significantly higher (P<0.05) level of bacteraemia in the broiler than in the Leghorn chicks. Chicks treated with 0.25 g/l or 0.125 g/l apramycin for 24 or 48 h before E. coli inoculation showed significantly lower cfu in the colon and caecum than untreated control chicks, but significantly higher cfu were found in the colon than in chicks treated with 0.5 g/l apramycin. Although in vitro preincubation of apramycin with ileum cells did not decrease the percentage of cells to which the bacteria adhered, the number of bacteria adhered per cell decreased significantly. Taken together, our in vitro and in vivo results show that apramycin is effective against E. coli by preventing colonization of the gut by the bacteria, which could lead to a reduction of colibacillosis in poultry.
{ "pile_set_name": "PubMed Abstracts" }
Globin chain synthesis in Hb J Baltimore-beta (+)-thalassemia. An American black family in whom hemoglobin J Baltimore and beta (+)-thalassemia genes coexisted is described. The proposita is a 23-year-old woman with a hemoglobin (Hb) level of 11.5 g/dl, microcytic, hypochromic indices, increased values of Hbs A2 and F, and alpha/non-alpha synthetic ratio of 1.52. Hbs A and J Baltimore (beta 16 Gly---Asp) constituted 12% and 81.3%, respectively, of her total hemoglobin. Her sister had a very similar peripheral blood picture, but Hbs A and J Baltimore constituted 6.8% and 85.5%, respectively, of her total hemoglobin, and the alpha/non-alpha synthetic ratio was 1.39. The mother had beta(+)-thalassemia trait only, a moderate degree of anemia, and greater synthetic imbalance (alpha/non-alpha raio of 1.73). These findings suggest that the presence of the Hb J Baltimore gene ameliorates the effects of a coexistent beta-thalassemia gene.
{ "pile_set_name": "PubMed Abstracts" }
Early nutrition and the development of immune function in the neonate. The present review will concentrate on the development of the gut-associated lymphoid tissue and the role of early nutrition in promoting immune function. The intestine is the largest immune organ in the body, and as such is the location for the majority of lymphocytes and other immune effector cells. The intestine is exposed to vast quantities of dietary and microbial antigens, and is the most common portal of entry for pathogens, some of which are potentially lethal. The development of normal immune function of the intestine is therefore vital for survival, and is dependent on appropriate antigen exposure and processing, and also an intact intestinal barrier. In early life innate mechanisms of defence are probably more important than active or adaptive mechanisms in responding to an infectious challenge, since the healthy neonate is immunologically naïve (has not seen antigen) and has not acquired immunological memory. During this period maternal colostrum and milk can significantly augment resistance to enteric infections. The mechanisms of enhancing disease resistance are thought to be passive, involving a direct supply of anti-microbial factors, and active, by promoting the development of specific immune function. A tolerance response to dietary and non-invasive antigens is generally induced in the gut. However, it must also be able to mount an adequate immune response to ensure clearance of foreign antigens. It is now recognized that regulation of tolerance and active immune responses is critical to health, and failure to regulate these responses can lead to recurrent infections, inflammatory diseases and allergies. The education of the immune system in early life is thought to be critical in minimizing the occurrence of these immune-based disorders. During this phase of development maternal milk provides signals to the immune system that generate appropriate response and memory. One factor that has been proposed to contribute to the increase in the incidence of immune-based disorders, e.g. atopic diseases in Western countries, is thought to be the increased prevalence of formula-feeding.
{ "pile_set_name": "PubMed Abstracts" }
Cardiovascular effects of the essential oil of Croton zehntneri leaves in DOCA-salt hypertensive, conscious rats. This study investigated the cardiovascular effects of the essential oil of Croton zehntneri (EOCZ) in deoxycorticosterone-acetate (DOCA)-salt hypertensive rats. Furthermore, in vitro experiments using isolated thoracic aortic rings were performed to assess the vascular effects of the EOCZ. In conscious hypertensive rats, intravenous (i.v.) injections of EOCZ (1-20 mg/kg) induced rapid (2-4 s) and dose-dependent hypotension and bradycardia (phase 1). The hypotension was followed by a significant pressor effect that was more evident at the higher doses (10 and 20 mg/kg) of EOCZ. Hypotension and bradycardia of EOCZ (phase 1) were abolished and respectively reversed into pressor and tachycardiac effects by methylatropine (1 mg/kg, i.v.) pretreatment. In isolated endothelium-intact aortic preparations, increasing concentrations (1-1000 microg/mL) of EOCZ relaxed the potassium-induced contraction in a concentration-dependent manner with an IC50 (geometric mean [95% confidence interval]) value of 202.0 [92.0-443.7] microg/mL. This vasorelaxant effect remained unaffected by either mechanical removal of functional vascular endothelium (IC50 = 189.0 [159.4-224.7] microg/mL) or the addition of atropine (1 microM) (IC50 = 158.6 [79.8-316.2] microg/mL) in the perfusion medium. These data show that i.v. administration of EOCZ in DOCA-salt hypertensive rats induces a vago-vagal reflex decreases in heart rate and blood pressure (phase 1). EOCZ may induce a second and delayed hypotension due to its direct endothelium-independent vasorelaxant effects, but it seems to be buffered by the pressor component (subsequent to phase 1) of EOCZ. This pattern of blood pressure and heart rate responses to EOCZ seems unaltered by DOCA-salt hypertension, as was similar to that previously reported in conscious normotensive rats.
{ "pile_set_name": "PubMed Abstracts" }
Thermoregulatory control of expired air temperature in diving harp seals. Expired air temperature (Tex), metabolic rate (MR), and skin (Ts) and body (Tb; rectal) temperatures were recorded in four or five young (1-2 yr) harp seals (Phoca groenlandica) in air [mean air temperature (Ta) = -30, -10, or 10 degrees C] and in water [mean water temperature (Tw) = 2.3 or 24.8 degrees C, with Ta = -30, -10, 0, or 10 degrees C]. Apparent lower critical temperature was below -10 degrees C in air. Above this Ta, mean MR was 5.85 W.kg-0.75 (2.23 W.kg-1), while mean MR was 12.56 W.kg-0.75 (4.69 W.kg-1) at Ta -30 degrees C. When seals were immersed in water of 2.3 degrees C, mean MR was 6.13 W.kg-0.75 (2.31 W.kg-1), regardless of Ta. At Ta -30, -10, and 10 degrees C, mean Tex in air were 9.5, 13.0, and 25.0 degrees C, respectively. The corresponding values for seals in water (Tw = 2.3 degrees C) were 8.0, 9.5, and 15.5 degrees C, respectively. The low Tex recorded at Ta -30 and -10 degrees C in air and at all Ta in water (Tw = 2.3 degrees C) suggests that heat was conserved by nasal heat exchange. At Ta 10 degrees C, mean Tex of seals in air was approximately 10 degrees C higher than mean Tex of seals in water (Tw = 2.3 degrees C). Furthermore, seals subjected to a Tw of 24.8 degrees C at Ta 0 degrees C had a mean Tex 10 degrees C higher than when subjected to Tw 2.3 degrees C at the same Ta. These observations suggest that Tex in seals is under thermoregulatory control. In a series of forced dives of up to 5-min duration Tex was found to be the same before and after the dive regardless of dive duration and Ta.
{ "pile_set_name": "PubMed Abstracts" }
Cold, pH and salt tolerant Penicillium spp. inhabit the high altitude soils in Himalaya, India. Twenty five fungal cultures (Penicillium spp.), isolated from soil samples from the high altitudes in the Indian Himalayan region, have been characterized following polyphasic approach. Colony morphology performed on five different media gave varying results; potato dextrose agar being the best for the vegetative growth and sporulation as well. Microscopic observations revealed 18 isolates to be biverticillate and 7 monoverticillate. Based on the phenotypic characters (colony morphology and microscopy), all the isolates were designated to the genus Penicillium. Exposure to low temperature resulted in enhanced sporulation in 23 isolates, while it ceased in case of two. The fungal isolates produced watery exudates in varying amount that in many cases increased at low temperature. All the isolates could grow between 4 and 37 °C, (optimum 24 °C), hence considered psychrotolerant. While all the isolates could tolerate pH from 2 to 14 (optimum 5-9), 7 isolates tolerated pH 1.5 as well. While all the fungal isolates tolerated salt concentration above 10 %; 10 isolates showed tolerance above 20 %. Based on ITS region (ITS1-5.8S-ITS2) analysis the fungal isolates belonged to 25 different species of Penicillium (showing similarity between 95 and 100 %). Characters like tolerance for low temperature, wide range of pH, and high salt concentration, and enhancement in sporulation and production of secondary metabolites such as watery exudates at low temperature can be attributed to the ecological resilience possessed by these fungi for survival under low temperature environment of mountain ecosystem.
{ "pile_set_name": "PubMed Abstracts" }
Randomized trial comparing continuous subcutaneous insulin infusion and conventional insulin therapy in type II diabetic patients poorly controlled with sulfonylureas. To compare the effects of continuous subcutaneous insulin infusion (CSII) and conventional insulin therapy (CIT) in patients with poorly controlled sulfonylurea-treated diabetes mellitus. Twenty-five patients aged 40-65 yr and poorly controlled with sulfonylureas and without severe diabetic complications comprised the study group. Five patients left the study (3 achieved satisfactory glycemic control without insulin, 1 defaulted, 1 developed ketonuria). Ten patients were treated with CSII and 10 with CIT. Outpatient treatment consisted of CIT (twice-daily injections of regular and NPH insulin) or CSII (basal infusion and prandial boluses of regular insulin). Glycosylated hemoglobin improved with both methods of insulin delivery (P less than 0.01), but 8 of 10 CSII-treated patients achieved satisfactory glycemic control (HbA1 less than 50 mmol hydroxymethylfurfural/mol Hb), whereas only 3 of 10 CIT-treated patients achieved this (P less than 0.05). Weight gain, insulin dosage, and prevalence of hypoglycemia were similar in the two groups. Retinal deterioration occurred in one CSII-treated patient and three CIT-treated patients, but there were no episodes of infusion site infection or metabolic decompensation. Patients' satisfaction with treatment improved during insulin therapy (P less than 0.02), and significant changes in beliefs about diabetes and its treatment were observed in CSII-treated patients (P less than 0.05). Glycemic control improved with both methods of insulin treated patients achieved satisfactory glycemic control (HbA1 less than 50 mmol hydroxymethylfurfural/mol Hb), whereas only 3 of 10 CIT-treated patients achieved this CSII. Patients' satisfaction with treatment improved during insulin therapy.
{ "pile_set_name": "PubMed Abstracts" }
A repeatable inverse kinematics algorithm with linear invariant subspaces for mobile manipulators. On the basis of a geometric characterization of repeatability we present a repeatable extended Jacobian inverse kinematics algorithm for mobile manipulators. The algorithm's dynamics have linear invariant subspaces in the configuration space. A standard Ritz approximation of platform controls results in a band-limited version of this algorithm. Computer simulations involving an RTR manipulator mounted on a kinematic car-type mobile platform are used in order to illustrate repeatability and performance of the algorithm.
{ "pile_set_name": "PubMed Abstracts" }
[An epidemiological study regarding the hearing acuity of residents in the area with high level of aircraft noise: results of hearing tests conducted in the vicinity of Kadena Air Base]. Hearing tests, primary and secondary, were conducted in two communities vicinal to Kadena US Air Base in Okinawa from May 1996 to July 1998. The noise exposure expressed in WECPNL as designated by the Defense Facilities Administration Agency ranged from 85 to 95 and above. A total of 2035 subjects aged between 25 and 69 years inclusive were considered eligible for inclusion in this study and among them 137 males and 206 females underwent the primary test. Before the test, subjects were asked about hearing difficulty, tinnitus, otological anamnesis and past experience of noise exposure at work and/or hobbies. The primary test was a pure tone audiometry using the ascending method of limits with 5 dB step at 7 test frequencies of 0.5 to 8 kHz. Forty individuals who were judged to have possible noise induced hearing loss were sent to Okinawa Chubu Hospital as subjects for the secondary test. The secondary test consisted of pure tone audiometry with 1 dB step at 9 test frequencies with the addition of 3 kHz and 6 kHz to the primary test frequencies, a Short Increment Sensitivity Index (SISI), test, tympanometry and audioscan audiometry. Based on test findings 12 subjects were considered to have noise induced hearing loss. The examiners interviewed the 12 subjects again to confirm that they had not experienced habitual or repeated intense noise exposure other than aircraft noise exposure around their homes. The geographical distribution of the subject's residences showed their proximity to the airfield, which strongly suggests that the cause of hearing loss may be exposure to aircraft noise from Kadena Air Base.
{ "pile_set_name": "PubMed Abstracts" }
Sonography-guided percutaneous microwave ablation of intrahepatic primary cholangiocarcinoma. To evaluate the efficacy and safety of sonography-guided percutaneous microwave ablation of intrahepatic primary cholangiocarcinoma. From May 2006 to March 2010, 15 patients (11 men, 4 women; mean age, 57.4 years) with 24 histologically proven intrahepatic primary cholangiocarcinoma lesions (mean tumor size, 3.2±1.9 cm; range, 1.3-9.9 cm) were treated with microwave ablation. Thirty-eight sessions were performed for 24 nodules in 15 patients. The follow-up period was 4-31 months (mean, 12.8±8.0 months). The ablation success rate, the technique effectiveness rate, and the local tumor progression rate were 91.7% (22/24), 87.5% (21/24), and 25% (6/24) respectively according to the results of follow-up. The cumulative overall 6, 12, 24 month survival rates were 78.8%, 60.0%, and 60.0%, respectively. Major complication occurred including liver abscess in two patients (13.3%) and needle seeding in one patient (6.7%). Both complications were cured satisfied with antibiotic treatment combined to catheter drainage for abscess and resection for needle seeding. The minor complications and side effects were experienced by most patients which subsided with supportive treatment. Microwave ablation can be used as a safe and effective technique to treat intrahepatic primary cholangiocarcinoma.
{ "pile_set_name": "PubMed Abstracts" }
Local level sustainability policies in the Baltic Sea area: Local Agenda 21 within the Union of the Baltic Cities network. Local Agenda 21 (LA21) processes have 2 central goals. i) On the basis of some of the empirical evidence in this study, the primary goal is to improve democratic (environmental) policy-making processes in such a manner that a larger share of the population will be able to participate in planning and decision making and will also be able to understand the consequences of these decisions. ii) The LA21 processes seek to improve (at least indirectly) the broadly defined environmental situation locally in a manner that takes into account both the local and the global contexts. The first part of this article discusses the concept and methods of LA21 and sheds light on the different action areas that are central to the Baltic LA21 processes. In addition, the study will describe and display the LA21 situation within one network of cities, the Union of the Baltic Cities (UBC). Networking, including transfer of information, models and ideas, has been among the main tools for the diffusion of LA21 ideas especially into newly democratized societies. Finally, the article will conclude with an overall assessment of the LA21 situation on the Baltic rim.
{ "pile_set_name": "PubMed Abstracts" }
Torsades de pointes ventricular tachycardia induced by clarithromycin and disopyramide in the presence of hypokalemia. We report a 76-year-old woman who developed TdP ventricular tachycardia induced by combined use of clarithromycin and disopyramide. She had a history of myocardial infarction 5 years earlier and has taken disopyramide for supraventricular arrhythmias. In addition, she had taken clarithromycin for upper respiratory tract infection. On admission, an ECG showed prolongation of QTc interval to 0.71 seconds and self-terminating TdP occurred several times. Disopyramide was metabolized by the cytochrome enzyme CYP3A4 and clarithromycin competitively inhibits this enzyme, probably resulting in an increase in plasma concentration of disopyramide. We should consider this possibility when prescribing clarithromycin in combination with antiarrhythmic agent disopyramide.
{ "pile_set_name": "PubMed Abstracts" }
Subcellular distribution and immunocytochemical localization of protein kinase C in myocardium, and phosphorylation of troponin in isolated myocytes stimulated by isoproterenol or phorbol ester. Protein kinase C (PKC) catalytic activity was found in the cytosol, sarcolemma and sarcoplasmic reticulum, and PKC immunoreactivity was found in the striated regions and sarcolemma of rat hearts. Enhanced phosphorylation of troponin T and, to a lesser extent, troponin I was noted in isolated rat cardiac myocytes incubated with PKC activator phorbol ester, but only the phosphorylation of troponin I was stimulated by isoproterenol. It is suggested that PKC-mediated phosphorylation of troponin might be involved in regulation of myocardial function or in pathophysiology of the heart.
{ "pile_set_name": "PubMed Abstracts" }
Effect of delta 9-tetrahydrocannabinol on short-term memory in the rat. We have reported that marihuana and its principal psycoactive compound, delta 9-tetrahydrocannabinol (delta 9-THC) produce alterations in several cerebral areas after acute treatment. Based on the involvement of 5-hydroxytryptamine (5-HT) on memory and learning and the reported effects of delta 9-THC on short-term memory, we designed an experiment to evaluate the memory performance and its possible relationship with serotonergic alterations after delta 9-THC administration. Male Wistar rats received an acute oral dose of THC (5 mg/kg). Short-Term memory was tested on a radial 8-arm maze with a 5 s delay, after 35 days of training. The animals were food deprived and adjusted for growth. 5-HT and its metabolite, 5-HIAA, levels were measured in cerebral cortex, dorsal hippocampus, ventral hippocampus, rostral neoestriatum and amygdala basal nucleus, by HPLC-ED. The experiment indicates an impairment of short-term memory in the radial maze test after delta 9-THC administration. The control group performed the test without errors, while the treated group made a significant number of errors (Z = 0.019, Mann-Whitney test). This behavioral effect did not seem to be related to serotonergic alterations, as the 5-HT turnover rate was not different between treated and control animals.
{ "pile_set_name": "PubMed Abstracts" }
The effect of temperature changes on in vitro slow wave activity in the equine ileum. Slow waves are rhythmic pacemaker currents generated by the gastrointestinal pacemaker cells, the interstitial cells of Cajal, and represent the rate-limiting step for small intestinal smooth muscle contractions. Therefore, factors that affect slow wave activity may also influence contractile activity. It is not known how temperature changes may influence slow wave activity in the horse. This could be of relevance during colic surgery if cooling of exposed intestine resulted in reduced slow wave activity potentially exacerbating post operative ileus. To evaluate the effect of temperature changes on in vitro slow wave activity of normal equine ileum using intracellular recording techniques. In vitro experimental study. A segment of ileum was collected immediately following euthanasia from 9 horses for reasons unrelated to the gastrointestinal tract. Intracellular recordings of membrane potentials were made from individual smooth muscle cells. The temperature of the tissue bath was altered during the course of each experiment across a range of 27-41°C. All data were recorded and stored using a computer-interfaced acquisition system. A software package was used to analyse slow wave frequency, duration, amplitude and resting membrane potential. In all 9 horses, slow wave frequency was highly temperature sensitive and approximately linearly related to the temperature over the range studied, increasing by 0.5 cycles/min for each 1°C increase in temperature (P<0.001). The initial slow wave frequency resumed when the temperature was returned to 37°C. The recovery time appeared to be directly related to the duration for which the temperature had been changed. Slow wave frequency in the equine ileum is highly temperature sensitive. As post operative ileus is a major cause of morbidity and mortality in the horse, the negative effect of lower temperatures on slow waves, and therefore contractile activity, should be considered.
{ "pile_set_name": "PubMed Abstracts" }
An acute stressor enhances sensitivity to a chemical irritant and increases 51CrEDTA permeability of the colon in adult rats. We investigated the effect of prior acute stress on colonic permeability induced by a chemical irritant known to induce symptoms similar to inflammatory bowel disease in rodents. Adult male rats (n = 12) were stressed by a single session of ten unpredictable, uncontrollable foot shocks, and half were home cage controls (n = 12). Twenty-nine days later, half of each treatment group was exposed to 4% DSS (dextran sulphate sodium) solution in their drinking water for 48 hours while half received pure water over two periods separated by 17 days. After food deprivation overnight and light isoflurane anaesthesia the following morning, the animals were given a colonic infusion of 2000 nCi (nanocurie) 51CrEDTA (51Cr-labelled ethylenediaminetetraacetic acid) and then placed individually in metabolic cages for a six hours continuous urine collection. Radioactivity in urine was measured by a gamma counter and percentage recovery of 51CrEDTA calculated as an indicator of colonic mucosal permeability. Results concluded that pre-shocked animals exposed to DSS showed significantly higher mucosal permeability than the pre-shocked animals given water, and the non-shocked animals given either DSS or water. Pre-shock in combination with two exposures to a chemical irritant separated by 17 days had a pronounced effect on colonic permeability, indicating that stress should be considered a possible initiating or contributory factor to increased intestinal permeability related to a mucosal challenge.
{ "pile_set_name": "PubMed Abstracts" }
Combined depth and subdural electrode investigation in uncontrolled epilepsy. We used both depth and subdural electrodes to obtain localization of the seizure focus in 47 medically refractory epileptic patients. Seizures were localized in 33 patients. Onset was consistently localized by the depth electrodes in 23 patients, was variable or simultaneous in depth and subdural electrodes in 6 (in the same lobe), and was consistently localized to subdural electrodes in 4. All patients localized with subdural electrodes were extratemporal and 3 of the 4 had lesions on imaging studies which helped guide location of electrode placement. Eighty-seven percent of temporal lobe seizures began in hippocampus (recorded by the depth electrode), and 80% were eventually propagated to the ipsilateral temporal neocortex (recorded by the subdural electrode). In 8 patients with bilateral temporal depth and subdural recording, seizures never spread to the contralateral neocortex before the ipsilateral neocortex. Subdural electrodes were 20% less sensitive than depth electrodes in detection of seizures beginning in hippocampus but were accurate when lateralized. Variable or simultaneous unilateral neocortical versus hippocampal temporal lobe seizure onset, determined by the combined study, was significantly correlated with less favorable seizure control after anteromedial temporal lobectomy and hippocampectomy.
{ "pile_set_name": "PubMed Abstracts" }
A new method of culturing and transferring iris pigment epithelium. To optimize a culture technique and transfer iris pigment epithelial (IPE) cells for cellular studies in vitro. Porcine iris tissues were obtained, and IPE cells were isolated and cultured at high densities by plating them in the form of drops. Spherically shaped structures containing a high concentration of cells were formed after 7 to 10 days of culture. Cells were subcultured by transferring spheres to new culture dishes without employing enzymatic dissociation. The purity of IPE cells was determined by pigmentation and cytokeratin labeling. Proliferation was assessed by incorporation of 5-bromo-2'-deoxyuridine. Cellular structure was analyzed under the light and electron microscopes and function was assayed by rod outer segment phagocytosis. Iris pigment epithelial cells, when cultured at high densities, tended to form elevated spherical structures containing viable cells. The cultured cells were pigmented and showed positive labeling with a monoclonal cytokeratin antibody. The IPE cells proliferated and migrated from the spheres to form monolayers. Cells originating from the transferred spheres also continued to proliferate and to migrate in a similar manner to the originally cultivated cells to form monolayers after 7 to 10 days. These cells were able to phagocytose rod outer segments. This new method provides a simple method of culturing a large quantity of IPE cells. The high yield of pure IPE cells and the ease of transfer provide an ideal means to study them at the cellular level.
{ "pile_set_name": "PubMed Abstracts" }
Unusual site of guide-wire entrapment during central venous catheterization. We are reporting a case of possible entrapment of guide wire in the region of tricuspid valve, which made it impossible to remove the guide wire from internal jugular (IJ) vein for a short while. Awareness about this rare complication is emphasized.
{ "pile_set_name": "PubMed Abstracts" }
[Genetic linkage of blood group, egg and serum protein and plumage color loci in chickens]. Genetic relationship of six blood group (A, B, C, D, E, x5), three egg (G2, G3, Ov) and one serum (Alb) protein loci and two plumage colour (I-dominant white, E-extended black) loci were investigated. 3250 gametes have been analysed for 21 loci combinations, 11 from them have never been studied on linkage. Blood group loci A, B, C, D, E, x5 segregated independently on egg protein loci G2, G3, and Ov, serum protein locus Alb and plumage colour locus E. No linkage was observed between blood group locus B and dominant white locus I. Close linkage for two egg protein loci G3 and Ov is confirmed. Independent segregation of investigated blood group, egg and serum protein loci suggests their localization on different autosomes in the chicken genome. The recent literature and the authors' data on genetic relationship between blood group, polymorphic protein loci and morphological traits are reviewed.
{ "pile_set_name": "PubMed Abstracts" }
Management of 1,590 consecutive cases of liver trauma. Between 1939 and 1974, more than 1,500 patients have been treated for penetrating or blunt liver trauma at our institution. Gunshot wounds and major blunt trauma have increased, stab wounds decreased, as percent of total. In most cases techniques other than partial hepatic resection were used, although this was performed in 49 instances. Choledochostomy was infrequently employed. Intracaval shunts were useful in 15 selected patients with massive hepatic, concomitant suprarenal vena caval, or hepatic vein injuries. The overall mortality of this group was 13.1%. The improvement in mortality from liver injuries is attributable to (1) early exploration for suspected intra-abdominal traumatic injury, (2) a conservative approach to the liver injury, and (3) the limitation of lobar resection, vascular cannulae, and afferent vascular compression to highly selected cases.
{ "pile_set_name": "PubMed Abstracts" }
Effect of age on survival in patients undergoing resection of hepatocellular carcinoma. The benefit of surgical intervention for cancer should be estimated in relation to the life expectancy of the general population. The aim of this study was to provide a measure of relative survival after hepatectomy for hepatocellular carcinoma (HCC). Consecutive patients with liver cirrhosis and HCC who underwent hepatectomy were divided into age quartiles for analysis. Short- and mid-term survival rates were used to estimate survival until death for all patients, in relation to age and other co-variables. Years of life lost (YLL) were estimated using a reference cohort, derived from the general population matched for sex, age and year of diagnosis. Some 919 patients were included in the study. The following age quartiles were identified: less than 60 years (229 patients), 60-66 years (230), 67-70 years (231) and over 70 years (229). Postoperative mortality rates were similar between age quartiles, as were survival rates up to 3 years (P = 0·404). A statistically significant reduction in 5-10-year survival rates was observed with ageing (P = 0·001). Relative survival calculation showed that the youngest age quartile (less than 60 years) experienced the longest entire postoperative lifespan (15·6 years) but also the greatest number of YLL (11·0 years). Patients aged over 70 years had the shortest entire postoperative lifespan (6·4 years) but also the smallest number of YLL (3·7 years). Although survival after liver resection for HCC is shortest in elderly patients, relative survival estimates suggest that hepatectomy can be of benefit in these patients, with a small loss of the entire individual lifespan.
{ "pile_set_name": "PubMed Abstracts" }
Simultaneous analysis of 2-methylimidazole, 4-methylimidazole, and 5-hydroxymethylfurfural potentially formed in fermented soy sauce by "quick, easy, cheap, effective, rugged, and safe" purification and UHPLC with tandem mass spectrometry. 2-Methylimidazole, 4-methylimidazole and 5-hydroxymethylfurfural are harmful by-products potentially formed via Maillard reaction in fermented soy sauce. The present study proposed a new method based on "quick, easy, cheap, effective, rugged, and safe" purification and ultra high performance liquid chromatography with tandem mass spectrometry for the simultaneous analysis of 2-methylimidazole, 4-methylimidazole and 5-hydroxymethylfurfural in fermented soy sauce. The sample was dissolved in water after addition of internal standard 4-methylimidazole-d6 and extracted with acetonitrile. After dehydration, it was centrifuged and the supernatant was subsequently purified using two sorbents namely primary-secondary amine and multi-walled carbon nanotube. Three target analytes were separated by gradient elution and determined under multiple reactions monitoring mode. The limit of detection, matrix effect, recovery and precision of the developed method were investigated. Results found that three target analytes displayed excellent linearity in concentration range of 1-250 μg/L. Limit of detection was in the range of 0.3-1 μg/kg for three target analytes. The mean recoveries for fermented soy sauce samples at three spiked concentrations were in the range of 91.2-112.5%, and the intra- and interday precision were in the ranges of 3.6-9.2 and 7.1-10.8%, respectively. This validated method was successfully applied to determine 2-methylimidazole, 4-methylimidazole and 5-hydroxymethylfurfural concentrations in fermented soy sauce.
{ "pile_set_name": "PubMed Abstracts" }
Vein of Galen Malformations: The Texas Children's Hospital Experience in the Modern Endovascular Era. Vein of Galen malformations (VOGM) comprise nearly a third of pediatric cerebrovascular anomalies, with potentially devastating neurological and systemic complications. Advances in endovascular therapies have dramatically improved outcomes compared to historical surgical treatments, and neurosurgeons are an essential component of the multidisciplinary critical care team. To retrospectively review pediatric patients with VOGM treated at Texas Children's Hospital (TCH), a quaternary referral center, over 15 yr, and present lessons learned in treating children with modern endovascular techniques. Charts from TCH were retrospectively reviewed for the past 15 yr. Patients with diagnosis including "Vein of Galen," "Vein of Galen malformation," "Vein of Galen aneurysmal malformation," or any abbreviations (ie, VOG, VOGM, VOGAM) were reviewed. Presentation, imaging, treatment specifics, and clinical outcomes were reported. There were 18 patients with VOGM managed at TCH from 2002 to 2018 with a total of 29 embolizations. Seventeen were performed with a single embolisate (NBCA or Onyx), and 12 with a combination. A dual lumen balloon catheter was used as an adjunct in 3 embolizations. Complications occurred in 5 embolizations (24%), including hemorrhage, embolisate migration, and femoral vessel occlusion. Surviving patients were followed for a mean of 38 mo, with 12 having normal or near-normal neurological development. VOGM can present with a myriad of neurological and systemic symptoms, potentially in extremis. Neurosurgical involvement in these cases is critical, as urgent treatment can be lifesaving. Patients may require multiple treatment sessions using a variety of endovascular tools and techniques.
{ "pile_set_name": "PubMed Abstracts" }
Factors for efficiency of the Salmonella/microsome mutagenicity assay. Factors were studied which modify the enzymatic capacity of mouse liver microsomal mixed-function oxidase to convert vinylidene chloride (1.1-dichloroethylene) (VDC) into mutagens in the Salmonella/microsome mutagenicity test. A microsomal fraction incorporated in soft agar layer converted VDC into mutagens during 7 h at a constant rate; these were detected with S. typhimurium TA100. In absence of VDC the enzymatic activity declined gradually to nil after 14 h of incubation at 37 degrees C. The presence of EDTA greatly enhanced the microsome-mediated mutagenicity of VDC and led to prolonged enzymatic viability, but only when liver fractions from phenobarbitone (PB) pretreated mice were used. The efficiency of the plate incorporation assay for the detection of mutagens is discussed in comparison with assays in liquid suspension.
{ "pile_set_name": "PubMed Abstracts" }
WITHDRAWN: NCAM and the FGF-Receptor. In this review, the structural biology of interaction between the neural cell adhesion molecule (NCAM) and the fibroblast growth factor (FGF) receptor is described and a possible mechanism of the FGF-receptor activation by NCAM is discussed. Most of the FGF-receptor molecules are thought to be constantly involved in a transient interaction with NCAM. However, the FGF-receptor becomes activated only when NCAM is involved the trans-homophilic binding (mediating cell-cell adhesion). The trans-homophilic binding between the NCAM molecules is believed to result in formation of either one- or two-dimensional 'zipper'-like arrays of the NCAM molecules, which leads to NCAM clustering and as a result to clustering of the FGF-receptor, which in turn may lead to its activation through a direct receptor-receptor dimerization (and thus activation) due to an increase in the local concentration of the receptor.
{ "pile_set_name": "PubMed Abstracts" }
Perivenular fibrosis as precursor lesion of cirrhosis. Thirty-four male alcoholics underwent sequential liver biopsies as part of their evaluation. Of 19 subjects with simple fatty livers, only three showed progression of liver disease: one developed perivenular fibrosis after two years; a second showed no progression after three years, but developed perivenular fibrosis after four years; the third subject likewise showed no progression after one year, but developed incomplete cirrhosis after six years. In contrast, of 15 subjects with perivenular fibrosis at the time of the initial biopsy, 13 progressed to more severe stages of liver disease during a one- to four-year follow-up interval. Nine developed fibrosis, one developed incomplete cirrhosis and three developed cirrhosis. Thus, patients with perivenular fibrosis at the fatty liver stage are likely to progress to more severe stages of alcoholic liver disease if they continue to consume alcohol.
{ "pile_set_name": "PubMed Abstracts" }
Prevalence of obesity in American Indians and Alaska Natives. Obesity is an important risk factor for cardiovascular diseases and non-insulin-dependent diabetes, which are chronic diseases that afflict American Indians and Alaska Natives today. Because American Indians are not represented in most national health and nutrition surveys, there is a paucity of data on actual prevalence of obesity in American Indians. We estimated prevalence of overweight and obesity for American Indian adults, school-age children, and preschool children from existing data. The prevalence of obesity in adults was estimated from self-reported weights and heights obtained from a special survey of American Indians performed as part of the 1987 National Medical Expenditure Survey. Prevalence of obesity in American Indians was 13.7% for men and 16.5% for women, which was higher than the US rates of 9.1% and 8.2%, respectively. Obesity rates in American Indian adolescents and preschool children were higher than the respective rates for US all-races combined.
{ "pile_set_name": "PubMed Abstracts" }
A new hypothesis for the pathophysiology of complex regional pain syndrome. Complex Regional Pain Syndrome (CRPS) has defied a clear unified pathological explanation to date. Not surprisingly, treatments for the condition are limited in number, efficacy and their ability to enact a cure. Whilst many observations have been made of physiological abnormalities, how these explain the condition and who does and doesn't develop CRPS remains unclear. We propose a new overarching hypothesis to explain the condition that invokes four dynamically changing and interacting components of tissue trauma, pathological pain processing, autonomic dysfunction (both peripheral and central) and immune dysfunction, primarily involving excessive and pathological activation of dendritic cells following trauma or atrophy. We outline pathophysiological changes that may initiate a cascade of events involving dendritic cells and the cholinergic anti-inflammatory pathway resulting in the condition, and the changes that maintain the condition into its chronic phase. This hypothesis should provide fertile ground for further investigations and development of new treatments that holistically address the nature of the disorder along its developmental continuum.
{ "pile_set_name": "PubMed Abstracts" }
A combination of nonionic surfactants and iontophoresis to enhance the transdermal drug delivery of ondansetron HCl and diltiazem HCl. The present work reports the evaluation of three nonionic ether-monohydroxyl surfactants (C(12)E(1), C(12)E(5,) and C(12)E(8)) as skin permeation enhancers in the transdermal drug delivery of two drugs: ondansetron hydrochloride and diltiazem hydrochloride, formulated as hydrogels. The enhancers are used alone, or in combination with iontophoresis (0.3 mA - 8h). After 1h of pre-treatment with 0.16 M enhancer solutions in propylene glycol (PG), passive and iontophoretic 24 h in vitro studies across dermatomed porcine skin were performed using vertical Franz diffusion cells. Data obtained showed that the nonionic surfactant C(12)E(5) was the most effective permeation enhancer, both for the passive process as well as for samples subjected to iontophoresis, resulting in cumulative amounts of ondansetron HCl after 24h of approximately 93 μg/cm(2) and 336 μg/cm(2), respectively. Data obtained using diltiazem HCl showed a similar trend. The use of the nonionic surfactant C(12)E(5) resulted in higher enhancement ratios (ER) in passive studies, but C(12)E(8) yielded slightly higher values of drug permeated (2678 μg/cm(2)) than C(12)E(5) (2530 μg/cm(2)) when iontophoresis was also employed. Skin integrity studies were performed to assess potential harmful effects on the tissues resulting from the compounds applied and/or from the methodology employed. Skin samples used in permeation studies visualized by light microscopy and Scanning Electron Microscopy (SEM) at different levels of magnification did not show significant morphological and structural changes, when compared to untreated samples. Complementary studies were performed to gain information regarding the relative cytotoxicity of the penetration enhancers on skin cells. MTS assay data using human epidermal keratinocytes (HEK) and human dermal fibroblasts (HDF) indicated that HEK are more sensitive to the presence of the enhancers than HDF and that the toxicity of these compounds is enhancer molecular weight dependent.
{ "pile_set_name": "PubMed Abstracts" }
Interaction of enzymes of the tricarboxylic acid cycle in Bacillus subtilis and Escherichia coli: a comparative study. We studied the interaction of the tricarboxylic acid cycle enzymes citrate synthase, isocitrate dehydrogenase and malate dehydrogenase in the bacteria Bacillus subtilis and Escherichia coli in vivo. In B. subtilis, the genes encoding citrate synthase, isocitrate dehydrogenase and malate dehydrogenase form an operon (citZ-icd-mdh) and predominantly are co-transcribed from a single promoter. In E. coli the corresponding genes gltA, icd and mdh do not form a transcription unit, are scattered around the chromosome and are expressed from different promoters. We found that co-transcription of genes and subsequent co-translation of the corresponding mRNAs promotes the formation of protein complexes and give support for the previous findings that in B. subtilis citrate synthase, isocitrate dehydrogenase and malate dehydrogenase form an enzyme complex (metabolon).
{ "pile_set_name": "PubMed Abstracts" }
Measurement of the frequency response of the electrostrictive nonlinearity in optical fibers. The electrostrictive contribution to the nonlinear refractive index is investigated by use of frequency-dependent cross-phase modulation with a weak unpolarized cw probe wave and a harmonically modulated pump copropagating in optical fibers. Self-delayed homodyne detection is used to measure the amplitude of the sidebands imposed upon the probe wave as a function of pump intensity for pump modulation frequencies from 10 MHz to 1 GHz. The ratio of the electrostrictive nonlinear coefficient to the cross-phase-modulation Kerr coefficient for unpolarized light is measured to be 1.58:1 for a standard step-index single-mode fiber and 0.41:1 for dispersion-shifted fibers, indicating a larger electrostrictive response in silica fibers than previously expected.
{ "pile_set_name": "PubMed Abstracts" }
Correlation of electrotonic monophasic action potential shortening with short-term memory in human atrium. To determine the presence of memory in human atria, we recorded monophasic action potential (MAP) at the high right atrium (HRA) in 21 patients. After reaching a steady state at 600 ms, HRA pacing was switched to the coronary sinus (CS) pacing to alter the activation sequence. After 20 minutes of CS pacing, pacing was continued at HRA to record the memory effect of CS pacing. Atrial memory was defined as the change in HRA MAP duration (MAPd) after 20 minutes of altered activation sequence. Baseline MAPd was 229 +/- 31 ms, which was shortened to 226 +/- 24 ms immediately after CS pacing. After 20 minutes of CS pacing, HRA MAPd during HRA pacing was 220 +/- 28 ms, which was significantly shorter than the baseline MAPd (P = 0.003). The degree of atrial memory was associated with the degree of initial electrotonic MAPd changes caused by the altered activation sequence. These results suggest that memory phenomenon exists in human atria, and it can be expressed as a change in MAPd.
{ "pile_set_name": "PubMed Abstracts" }
Infective endocarditis complicated with thalamic infarction and mycotic aneurysm rupture: a case report. A 39-year-old female with mitral valve prolapse experienced left side hemisensory disturbance four months after gastric surgery. Echocardiogram disclosed vegetation on the mitral valve and blood cultures showed growth of enterococcus. With a diagnosis of thalamic infarction complicating infective endocarditis, she was hospitalized for further treatment. After four weeks of antibiotic therapy, she developed sudden headache and obtundation. Imaging studies revealed intracerebral hemorrhage (ICH), resulting from mycotic aneurysm rupture. She survived and recovered after emergency craniotomy and evacuation of the hematoma. However, the ICH recurred six weeks later and the patient died after five days in a deep coma. Patients with mitral valve prolapse are common. Those who have systolic murmur or valvular thickening and redundancy are at particular risk of infective endocarditis and should receive antibiotic prophylaxis perioperatively as recommended by the American Heart Association. Clinical manifestations of infective endocarditis and its complications, as in our patient, are often trivial. Prompt diagnosis and intervention are crucial. In view of the poor prognosis associated with ICH due to mycotic aneurysm rupture, we suggest cerebral angiography be performed in patients presenting with focal neurologic deficits or with warning headache for early detection of accessible lesions for excision.
{ "pile_set_name": "PubMed Abstracts" }
Induction of CD25 expression in human B lymphocytes by pharmacological activators of cellular signalling pathways. IL-4 promotes simultaneous expression of both the CD23 and CD25 antigens in resting human B lymphocytes in a dose-dependent manner. Simultaneous three-colour flow cytometric analysis revealed that CD19+/CD23+/CD25+ triple-positive cells were derived from a CD19+/CD23-/CD25- pool, and that induction of CD23 required lower doses of IL-4 than did induction of CD25. Although the concentrations of IL-4 required for half-maximal up-regulation of CD23 (35 pM) and CD25 (150 pM) expression were different, the capacity of IL-4 to promote expression of the two markers could be mimicked by the same combination of pharmacological agents. Thus, maximal expression of CD23 and CD25 was obtained with a 30 (or 120) second pulse with phorbol ester and/or ionomycin followed by a sustained (20 minute) treatment with forskolin. Use of BAPTA to chelate intracellular calcium suggested that IL-4 driven CD25 expression required mobilization of intracellular Ca2+. Finally, down-regulation of cellular protein kinase C by chronic treatment of resting B lymphocytes with phorbol ester abolished the ability of IL-4 to elevate CD23 and CD25 expression; phorbol ester treatment similarly abrogated the ability of anti-CD40 and anti-Ig reagents to promote expression of CD25. The data are consistent with the proposal that IL-4 influences CD23 and CD25 expression via a similar signal transduction pathway which involves both protein kinase C activation and elevation of intracellular cAMP levels.
{ "pile_set_name": "PubMed Abstracts" }
Species, tissue and gender-related organochlorine bioaccumulation in white-sided dolphins, pilot whales and their common prey in the northwest Atlantic. Organochlorine concentrations were measured in white-sided dolphins, pilot whales, and their prey from the Gulf of Maine and used to identify species, tissue, and gender differences, and trophic transfer trends, in bioaccumulation. Polychlorinated biphenyl concentrations ([PCB]) in dolphin blubber (13 +/- 7.1 micrograms/g fresh wt.) were twice those in pilot whales, but pesticide concentrations (20 +/- 13 micrograms/g fresh) were similar between species. 4,4'-DDE, trans-non-achlor, Cl6(153) and Cl6(138) concentrations were highest. Skin tissues had more recalcitrant organochlorines than the internal organs. Male dolphins bioaccumulated higher concentrations of nonmetabolizable PCBs and hexachlorocyclohexane (HCH) isomers, whereas pilot whales had no gender-related differences in bioaccumulation. Pilot whales, mackerel, and herring had proportionately higher concentrations of DDTs, whereas [PCB] were higher in dolphins and squid. Although these odontocetes feed at the same trophic level and store a similar suite of contaminants, dolphins bioaccumulated higher and potentially hazardous 4,4'-DDE and PCB concentrations from food in their more geographically restricted range.
{ "pile_set_name": "PubMed Abstracts" }
ErbB-2 nuclear function in breast cancer growth, metastasis and resistance to therapy. Approximately 15-20% of breast cancers (BC) show either membrane overexpression of ErbB-2 (MErbB-2), a member of the ErbBs family of receptor tyrosine kinases, or ERBB2 gene amplification. Until the development of MErbB-2-targeted therapies, this BC subtype, called ErbB-2-positive, was associated with increased metastatic potential and poor prognosis. Although these therapies have significantly improved overall survival and cure rates, resistance to available drugs is still a major clinical issue. In its classical mechanism, MErbB-2 activates downstream signaling cascades, which transduce its effects in BC. The fact that ErbB-2 is also present in the nucleus of BC cells was discovered over twenty years ago. Also, compelling evidence revealed a non-canonical function of nuclear ErbB-2 as a transcriptional regulator. As a deeper understanding of nuclear ErbB-2 actions would be crucial to the disclosure of its role as a biomarker and a target of therapy in BC, we will here review its function in BC, in particular, its role in growth, metastatic spreading and response to currently available MErbB-2-positive BC therapies.
{ "pile_set_name": "PubMed Abstracts" }
Zinc and vitamin A supplementation in Indigenous Australian children hospitalised with lower respiratory tract infection: a randomised controlled trial. To evaluate the efficacy of supplementation with zinc and vitamin A in Indigenous children hospitalised with acute lower respiratory infection (ALRI). Randomised controlled, 2-by-2 factorial trial of supplementation with zinc and vitamin A. 187 Indigenous children aged < 11 years hospitalised with 215 ALRI episodes at Alice Springs Hospital (April 2001 to July 2002). Vitamin A was administered on Days 1 and 5 of admission at a dose of 50 000 IU (infants under 12 months), or 100 000 IU; and zinc sulfate was administered daily for 5 days at a daily dose of 20 mg (infants under 12 months) or 40 mg. Time to clinical recovery from fever and tachypnoea, duration of hospitalisation, and readmission for ALRI within 120 days. There was no clinical benefit of supplementation with vitamin A, zinc or the two combined, with no significant difference between zinc and no-zinc, vitamin A and no-vitamin A or zinc + vitamin A and placebo groups in time to resolution of fever or tachypnoea, or duration of hospitalisation. Instead, we found increased morbidity; children given zinc had increased risk of readmission for ALRI within 120 days (relative risk, 2.4; 95% CI, 1.003-6.1). This study does not support the use of vitamin A or zinc supplementation in the management of ALRI requiring hospitalisation in Indigenous children living in remote areas. Even in populations with high rates of ALRI and poor living conditions, vitamin A and zinc therapy may not be useful. The effect of supplementation may depend on the prevalence of deficiency of these micronutrients in the population.
{ "pile_set_name": "PubMed Abstracts" }
[The implementation process of a new model of intensive rehabilitation in a hospital setting: the development of an innovative practice within the context of integration of settings, services and treatment models]. This article describes the process of implementation of an internal intensive rehabilitation program at Douglas hospital for people with severe mental disorders. A discussion of contemporary paradigms of rehabilitation implies the integration of biological and psychosocial perspectives in the characterization and treatment of the pathology. The discussion of the reorganization of the entire rehabilitation services of the Program for severe mental disorders leads to specifying the organizational and regional context of the implementation. The axes of implementation in priority are the following : analysis of needs, training, reorganization of work and modification of the setting of care. These activities are implemented in reference to scientific developments that are empirically relevant and assessed regularly. Future challenges include the pursuit of integration of treatment models, of settings and services within the context of the hierarchy of mental health care in Québec.
{ "pile_set_name": "PubMed Abstracts" }
[Effects of ligaments and plantar fascia on the foot finite element analysis]. Some 3D finite element systemic models are currently established and used to simulate the foot biomechanical state. However, during most of these 3D foot finite element static analyses, ligaments and plantar fascia are generally defined by connecting the corresponding attachment points on the bones, and the spaces between the bones are fused together by solid elements with given cartilage stiffness to simulate the connection of bones. This "connection of bones" takes the place of the real interactions between neighbored bones and enhances the structure of foot, which possibly leads to the result that the effects of ligaments and other soft tissues are completely replaced by the effect of articular cartilages. Thereby, ligaments and other soft tissues maybe not play an inherent role in the finite element analysis. The objective of this study was to estimate whether there exists the effect of ligaments and plantar fascia on the biomechanical behaviors of the foot tissue stress distribution and foot structure deformation during the balanced standing stance and static finite element analysis.
{ "pile_set_name": "PubMed Abstracts" }
Fetal health stagnation: Have health conditions in utero improved in the United States and Western and Northern Europe over the past 150 years? Many empirical studies have shown that health conditions in utero can have long lasting consequences for health across the life course. However, despite this evidence, there is no clear consensus about how fetal health has changed in the very long run. This paper analyses historical birth weights and perinatal mortality rates to construct a coherent picture of how health conditions in utero have changed over the past 150 years. In short, the evidence suggests that fetal health has been relatively stagnant. Limited evidence on birth weights shows that they had already reached their current levels in North America and Northern and Western Europe by the late nineteenth century, and they have changed very little in between. Perinatal mortality rates have fallen dramatically since the late 1930s, but this decline was mainly caused by improvements in intrapartum treatments after the introduction of Sulfa drugs and antibiotics. Thus, the health benefits associated with the perinatal mortality decline were concentrated among those at risk and did not influence the population at large. Finding stagnant fetal health during a period when many other indicators of health improved dramatically is provocative and suggests two conclusions: either fetal health did not improve or the indicators used to measure fetal health, indicators still widely used today, may not accurately capture all aspects of health in utero. If fetal health has been stagnant, then better conditions in utero cannot explain cohort improvements in life expectancy over the twentieth century. If the indicators of fetal health are problematic, then researchers must move beyond birth weight and perinatal mortality to understand how developmental plasticity based on the prenatal environment influences later life health.
{ "pile_set_name": "PubMed Abstracts" }
Fraunhofer diffraction of atomic matter waves: electron transfer studies with a laser cooled target. We have constructed an apparatus combining the experimental techniques of cold target recoil ion momentum spectroscopy and a laser cooled target. We measure angle differential cross sections in Li(+)+Na-->Li+Na(+) electron transfer collisions in the keV energy regime with a momentum resolution of 0.12 a.u. yielding an order of magnitude better angular resolution than previous measurements. We resolve Fraunhofer-type diffraction patterns in the differential cross sections. Good agreement with predictions of the semiclassical impact parameter method is obtained.
{ "pile_set_name": "PubMed Abstracts" }
Beyond the river: the benefits of cooperation on international rivers. Management of international rivers can be a cause of conflict or cooperation between states. Benefits of cooperation include benefits to the ecological river, the economic river, the political river and the catalytic river. The challenges are in balancing the trade-offs between states.
{ "pile_set_name": "PubMed Abstracts" }
Clinical application and outcome of the internal mammary artery perforator (IMAP) free flap for soft tissue reconstructions of the upper head and neck region in three patients. The fasciocutaneous internal mammary artery perforator (IMAP) island flap allows for superior esthetical and functional skin cover in the head and neck region in combination with limited donor site morbidity. Its modification as a free flap allows reconstruction of more cranial defects. Three IMAP free flaps varying from 7 × 4 cm² to 10 × 6 cm² were transplanted in three patients with a mean age of 59 years (range, 54-69 years). Enhancement of the flap's vascular pedicle at least doubles the diameter of the internal mammary vessels to be anastomosed. Coverage with excellent texture and color match was uneventfully obtained and the flaps' donor sites were primarily closed in all three cases. Our experience proves the consistent feasibility of successful transplantation of the IMAP free flap. Because of its characteristics, we suggest contemplating the use of this flap in the upper head and neck region.
{ "pile_set_name": "PubMed Abstracts" }
[The hyperventilation syndrome]. Acute hyperventilation (HV) rarely poses diagnostic or therapeutic problems. Chronic hyperventilation, however, with vague and multiple symptomatology due to respiratory alkalosis and increased breathing work, is often overlooked or misinterpreted, though it is a very common disorder of the general patient population. Chronic HV is frequently associated with emotional disturbances such as anxiety, panic and depression, or with psychosomatic disorders such as irritable bowel, effort syndrome and chronic pain. The diagnosis of chronic HV relies primarily on taking of a thorough history and is confirmed by an HV provocation test and arterial or cutaneous measurements of pCO2. Therapeutic measurements include psychotherapy, psychoactive drugs (antidepressants and benzodiazepines), beta-blockers and modification of abnormal breathing patterns.
{ "pile_set_name": "PubMed Abstracts" }
Pediatric tracheostomy: timing of the first tube change. No consensus exists on appropriate timing for the first tracheostomy tube change. The purpose of this study is to evaluate the safety of early tracheostomy change in the pediatric population. A case series of all children undergoing tracheostomy at a tertiary children's hospital between 2008-2013 was retrospectively reviewed. A total of 151 children undergoing tracheostomy were identified. The average age was 48.1±66 months and median age was 10 months. The initial tracheostomy tube change occurred on postoperative day 3 (POD 3) in 65 children (43.0%) safely without any complications. Early tracheostomy tube change was safely performed in a significant portion of this population. Routine tube change on POD 3 in many children could save resources by reducing the length of ICU and hospital stays.
{ "pile_set_name": "PubMed Abstracts" }
Laparoscopic management of malignant ovarian cysts: a 78-case national survey. Part 1: Pre-operative and laparoscopic evaluation. This paper reports a retrospective multi-institutional French survey carried out in 1992 to determine the incidence of laparoscopic management of malignant ovarian cysts. Of 5307 ovarian lesions treated endoscopically, 78 were malignant (1.47%) including 60 borderline tumors and 18 ovarian cancers. In 33% of cases preoperative diagnosis indicated that the tumor was benign. Preoperative findings were suspicious in 59%. Laparoscopic treatment was puncture in 23% of cases, partial exeresis in 51% and total removal in 26%.
{ "pile_set_name": "PubMed Abstracts" }
[Surgery of adrenal tumors]. From 1983 to 2003 examination and surgical treatment were performed in 463 patients with different adrenal tumors. Hormone-active tumors were revealed in 249 of them, non-active - in 214. Combination of CT or MRT with study of adrenal hormones is the basis of the diagnosis. In different cases multispiral computed tomography, angiography, selected taking of blood from inferior caval vein, US- or CT-guided biopsy were used. Open surgery through thoracofrenolumbotomy was performed in 392 patients, videolaparoscopic surgery - in 71. Expediency of laparoscopic surgery in line with open surgery is demonstrated.
{ "pile_set_name": "PubMed Abstracts" }
Highly enantioselective organocatalytic direct aldol reaction in an aqueous medium. We have demonstrated that small organic molecules 1 and 2 catalyzed the direct aldol reaction of both acyclic and cyclic ketones with different aldehydes in an excess of water/brine. Excellent enantioselectivities up to >99% and diastereoselectivities up to 99% with very good yields were obtained by using much lower catalyst loadings (0.5 mol %).
{ "pile_set_name": "PubMed Abstracts" }
Coping, commitment, and attitude: quantifying the everyday burden of enuresis on children and their families. To develop and evaluate a parent-completed questionnaire for use by clinicians as part of routine care to assess the burden of diurnal and nocturnal enuresis on children and their families. The questionnaire consisted of items that measure the impact on the child and his/her parent, the child's coping ability and commitment to treatment, previous treatment success, family frustration and overall cohesion, and parental attitudes about enuresis and its treatment. Questionnaires (n = 208) were completed by parents during the child's scheduled office visit for enuresis at 5 specialty clinics across the United States. Traditional criteria were used to assess reliability and validity of the questionnaire, including analysis of variance. Success rates provide evidence that many of the items in the child scale (79%) and all items in the parent scale (100%) met stringent criteria. alpha values were.62 and.77, respectively. Statistically significant differences were observed for the scales across responses on all but 1 global item, the majority of parental attitude items, whether the child urinated at bedtime, and the number of pads used. These findings suggest that the child's coping ability and commitment and the family's overall cohesion and frustration with the problem influence parental perceptions about the impact of enuresis on the child and the family. Findings about the performance of the new measure were satisfactory and suggest that, after further refinement, it should prove as a useful tool for clinicians treating enuresis in children.
{ "pile_set_name": "PubMed Abstracts" }
Validation of the Portuguese version of the Clinical Impairment Assessment (CIA) in eating disorders' patients. The purpose of the study was to assess the psychometric properties of the Portuguese version of the Clinical Impairment Assessment (CIA) in eating disorders (ED) patients. The CIA is a 16-item brief self-reported instrument developed to assess psychosocial impairment secondary to EDs. The CIA was administered to a clinical sample of 237 women with EDs and a college sample of 196 women. The clinical sample completed the Eating Disorders Examination Questionnaire, the Beck Depression Inventory and the Outcome-45 Questionnaire. Reliability, confirmatory factor analysis, validity, and clinically significant change were calculated. Confirmatory factor analysis validated the original 3-factor structure showing an adequate model fit. CIA showed good psychometric properties with high internal consistency, good convergent validity with the EDE-Q, the OQ-45, and the BDI. For divergent validity, participants CIA scores in the clinical sample were significantly higher than in the non-clinical sample. ROC curve analysis provided a cutoff of 15. For known-groups validity participants' scoring above CIA cutoff reported significantly higher CIA scores. In addition, non-underweight participants and participants reporting the presence of dysfunctional ED behaviors had significantly higher CIA scores. Finally, for clinically significant change, a reliable change index of 5 points was obtained to consider a reliable change in the CIA global score. Our findings support the validity and clinical utility of the CIA as a good self-report measure to be used in both clinical and research settings. Level V. Cross-sectional descriptive study.
{ "pile_set_name": "PubMed Abstracts" }
Acute suppurative thyroiditis following fine-needle aspiration biopsy in an immunocompetent patient. The thyroid gland is remarkably resistant to infectious agents owing to several protective mechanisms. Acute suppurative thyroiditis after fine-needle aspiration (FNA) in an immunocompetent patient is very rare. We report the case of a 50-year-old immunocompetent male patient who presented with painful cervical swelling, fever, and chills after an FNA of the thyroid. His physical and laboratory examination suggested an acute suppurative thyroiditis. Repeat FNA results were consistent with thyroid abscess. Physicians should be aware of the probability of acute bacterial thyroiditis after FNA.
{ "pile_set_name": "PubMed Abstracts" }
Marfanoid habitus is a nonspecific feature of Perrault syndrome. The objective of this study was to report the clinical and biological characteristics of two Perrault syndrome cases in a Moroccan family with homozygous variant c.1565C>A in the LARS2 gene and to establish genotype-phenotype correlation of patients with the same mutation by review of the literature. Whole-exome sequencing was performed. Data analysis was carried out and confirmed by Sanger sequencing and segregation. The affected siblings were diagnosed as having Perrault syndrome with sensorineural hearing loss at low frequencies; the female proband had primary amenorrhea and ovarian dysgenesis. Both affected individuals had a marfanoid habitus and no neurological features. Both patients carried the homozygous variant c.1565C>A; p.Thr522Asn in exon 13 of the LARS2 gene. This variant has already been reported as a homozygous variant in three other Perrault syndrome families. Both affected siblings of a Moroccan consanguineous family with LARS2 variants had low-frequency sensorineural hearing loss, marfanoid habitus, and primary ovarian insufficiency in the affected girl. According to the literature, this variant, c.1565C>A; p.Thr522Asn, can be correlated with low-frequency hearing loss. However, marfanoid habitus was been considered a nonspecific feature in Perrault syndrome, but we believe that it may be more specific than considered previously. This diagnosis allowed us to provide appropriate management to the patients and to provide more accurate genetic counseling to this family.
{ "pile_set_name": "PubMed Abstracts" }
Analysis of publicly available LDLR, APOB, and PCSK9 variants associated with familial hypercholesterolemia: application of ACMG guidelines and implications for familial hypercholesterolemia diagnosis. PurposeFamilial hypercholesterolemia (FH) is an autosomal disorder of lipid metabolism presenting with increased cardiovascular risk. Although more than 1,700 variants have been associated with FH, the great majority have not been functionally proved to affect the low-density lipoprotein receptor cycle. We aimed to classify all described variants associated with FH and to establish the proportion of variants that lack evidence to support their pathogenicity.MethodsWe followed American College of Medical Genetics and Genomics (ACMG) guidelines for the classification, and collected information from a variety of databases and individual reports. A worldwide overview of publicly available FH variants was also performed.ResultsA total of 2,104 unique variants were identified as being associated with FH, but only 166 variants have been proven by complete in vitro functional studies to be causative of disease. Additionally, applying the ACMG guidelines, 1,097 variants were considered pathogenic or likely pathogenic. Only seven variants were found in all five continents.ConclusionThe lack of functional evidence for about 85% of all variants found in FH patients can compromise FH diagnosis and patient prognosis. ACMG classification improves variant interpretation, but functional studies are necessary to understand the effect of about 40% of all variants reported. Nevertheless, ACMG guidelines need to be adapted to FH for a better diagnosis.
{ "pile_set_name": "PubMed Abstracts" }
Canine leishmaniasis. A review based on 95 cases in The Netherlands. The clinically relevant aspects of canine leishmaniasis are reviewed. Included are data from 92 dogs imported from the Mediterranean basin and at least 2 autochthonous cases. New aspects on pathogenesis are presented, including evidence that canine leishmaniasis is an immune complex disease. Therapy with meglumine antimonate (Glucantime) is evaluated. The hazards of imported canine leishmaniasis for public health are discussed.
{ "pile_set_name": "PubMed Abstracts" }
Chronic therapy with nipradilol, a beta-adrenergic blocker, attenuated left ventricular remodeling following myocardial infarction in rats. We determined whether chronic treatment with nipradilol, a beta-blocker with vasodilating action, reduces left ventricular cavity dilation (LV remodeling) following myocardial infarction and improves cardiac performance. Myocardial infarction was produced by coronary artery ligation in 16-week-old female rats and then the rats were treated for 3-4 months with nipradilol (10 mg/kg/day) or vehicle (0.5% carboxymethylcellulose). The effect of nipradilol on LV remodeling was evaluated by assessing the left ventricular end-diastolic volume index (LVEDVI) and passive pressure-volume relation curve. Since LVEDVI depends on the infarct size, LVEDVI was compared between the vehicle- and nipradilol-treated rats with similar infarct size (10-40%). At 3-4 months after myocardial infarct production, the left ventricular end-diastolic volume index in the vehicle-treated rats with myocardial infarction was significantly increased, compared with that in the sham-operated rats without infarction. The nipradilol-treated rats had a significantly smaller left ventricular volume index than the vehicle-treated rats (2.04 +/- 0.16 ml/kg in the vehicle-treated group vs 1.36 +/- 0.10 ml/kg in the nipradilol-treated group, P < 0.01). The maximum cardiac index achieved by volume loading as an index of cardiac performance was significantly greater in the nipradilol group than the vehicle group (254.5 +/- 12.6 ml/min kg in the vehicle group vs 347.9 +/- 20.2 ml/min kg in the nipradilol group, P < 0.01). These results suggest that chronic treatment of nipradilol attenuated left ventricular cavity dilation after myocardial infarction and improved cardiac performance.
{ "pile_set_name": "PubMed Abstracts" }
Anhedonia and depressed mood in adolescence: course, stability, and reciprocal relation in the TRAILS study. Adolescence is marked by increases in the incidence of major depression (MDD), a disorder recognized as one of the leading causes of disability. Anhedonia and depressed mood predict both onset and chronicity of major depression (MDD), but have never been studied together longitudinally in the general adolescent population. The present study examined (1) the course and the stability of anhedonia and depressed mood and (2) their cross-sectional and longitudinal relations during adolescence. The study cohort consisted of 2,230 adolescents. Anhedonia and depressed mood were assessed with items of the YSR and ASR self-report forms at four measurement waves between ages 11 and 19. The proportion of adolescents reporting anhedonia decreased between ages 11 and 19, while the proportion of female adolescents reporting depressed mood increased. The stability of anhedonia and the cross-sectional association between anhedonia and depressed mood was larger at age 19 than at age 11. We found a mutual association between anhedonia and depressed mood without a clear temporal sequence. The presence of anhedonia at the end of adolescence might put adolescents at increased risk for MDD given the increasingly stronger stability and association with depressed mood. This suggests that it becomes more difficult to prevent MDD during late adolescence compared with early and middle adolescence.
{ "pile_set_name": "PubMed Abstracts" }
Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. The standard treatment for patients with multiple myeloma who are not candidates for high-dose therapy is melphalan and prednisone. This phase 3 study compared the use of melphalan and prednisone with or without bortezomib in previously untreated patients with multiple myeloma who were ineligible for high-dose therapy. We randomly assigned 682 patients to receive nine 6-week cycles of melphalan (at a dose of 9 mg per square meter of body-surface area) and prednisone (at a dose of 60 mg per square meter) on days 1 to 4, either alone or with bortezomib (at a dose of 1.3 mg per square meter) on days 1, 4, 8, 11, 22, 25, 29, and 32 during cycles 1 to 4 and on days 1, 8, 22, and 29 during cycles 5 to 9. The primary end point was the time to disease progression. The time to progression among patients receiving bortezomib plus melphalan-prednisone (bortezomib group) was 24.0 months, as compared with 16.6 months among those receiving melphalan-prednisone alone (control group) (hazard ratio for the bortezomib group, 0.48; P<0.001). The proportions of patients with a partial response or better were 71% in the bortezomib group and 35% in the control group; complete-response rates were 30% and 4%, respectively (P<0.001). The median duration of the response was 19.9 months in the bortezomib group and 13.1 months in the control group. The hazard ratio for overall survival was 0.61 for the bortezomib group (P=0.008). Adverse events were consistent with established profiles of toxic events associated with bortezomib and melphalan-prednisone. Grade 3 events occurred in a higher proportion of patients in the bortezomib group than in the control group (53% vs. 44%, P=0.02), but there were no significant differences in grade 4 events (28% and 27%, respectively) or treatment-related deaths (1% and 2%). Bortezomib plus melphalan-prednisone was superior to melphalan-prednisone alone in patients with newly diagnosed myeloma who were ineligible for high-dose therapy. (ClinicalTrials.gov number, NCT00111319.)
{ "pile_set_name": "PubMed Abstracts" }
Poorly differentiated adenocarcinoma of the rectum in a nephrotic patient with focal segmental glomerulosclerosis. We report herein a case of poorly differentiated adenocarcinoma of the rectum occurring in a nephrotic patient with focal segmental glomerulosclerosis. The neoplasm which first appeared to be a submucosal tumor occurred in a 29-year old Japanese man with a nephrotic syndrome for 2 years and 6 months. Autopsy disclosed a large tumor located between the rectum and urinary bladder. Renal specimens showed changes consistent with focal segmental glomerulosclerosis.
{ "pile_set_name": "PubMed Abstracts" }
Is amodiaquine failing in Rwanda? Efficacy of amodiaquine alone and combined with artesunate in children with uncomplicated malaria. We investigated the safety and efficacy of amodiaquine alone (AQ) and combined with artesunate (AQ + AS) in 308 Rwandan children 6-59 months old with uncomplicated Plasmodium falciparum malaria attending three sentinel sites. The two treatment regimes were well tolerated and no serious adverse events were recorded. After excluding new infections, children treated with AQ + AS had fewer clinical failures at day 28 after treatment than those treated with AQ alone: OR = 0.20 [95% CI: 0.06-0.57 (P = 0.001)]. Total (parasitological and clinical) failure was also significantly less frequent in the AQ + AS group: OR = 0.34 [95% CI: 0.17-0.67 (P = 0.001)]. When adjusting for study site, the hazard ratio for treatment failure was 0.37 [95% CI: 0.20-0.68 (P = 0.001)]. Combining AQ with AS increases the efficacy of the treatment but the apparent increase of AQ resistance observed in just a 1-year period is worrying and casts doubts on the suitability of implementing AQ + AS as first-line treatment in Rwanda. Alternative treatments should be identified and tested.
{ "pile_set_name": "PubMed Abstracts" }
Obesity in Switzerland: a critical assessment of prevalence in children and adults. The objective was to analyze the situation in Switzerland regarding the prevalence of overweight or obesity in children, adolescents and adults. The data were compared with France, an adjacent much larger country. The results showed that there is a definitive lack of objective information in Switzerland on the prevalence of obesity at different ages. As in other European studies, the fact that many national surveys are classically based on subject interviews (self-reported weights and heights rather than measured values) implies that the overweight/obesity prevalence is largely underestimated in adulthood. For example, in a recent Swiss epidemiological study, the prevalence of obesity (BMI greater than 30 kg/m(2)) averaged 6-7% in young men and women (25-34 y), the prevalence being underestimated by a factor of two to three when body weight was self-reported rather than measured. This phenomenon has already been observed in previous European studies. It is concluded that National Surveys based on telephone interviews generally produce biased obesity prevalence results, although the direction of the changes in prevalence of obesity and its evolution with repeated surveys using strict standardized methodology may be evaluated correctly. Therefore, these surveys should be complemented by large-scale epidemiological studies (based on measured anthropomeric variables rather than declared) covering the different linguistic areas of Switzerland. An epidemiological body weight (BMI) monitoring surveillance system, using a harmonized methodology among European countries, would help to accurately assess differences in obesity prevalence across Europe without methodological bias. It will permit monitoring of the dynamic evolution of obesity prevalence as well as the development of appropriate strategies (taking into account the specificity of each country) for obesity prevention and treatment.
{ "pile_set_name": "PubMed Abstracts" }
[Matter production and storage of Leymus chinensis clonal populations in restoration succession process of flooded meadow in Songnen Plain of China]. In this paper, the tiller matter production and the rhizome matter storage of Leymus chinensis clonal populations in the patches with radius of 0.5, 1, 3, 5 and 10 m were studied in the restoration succession process of flooded meadow in Songnen Plain. The results indicated that in each patch, 1 and 2 age classes had the most tiller matter production, while in the patches except in the center of 10 m patch, the rhizome matter storage of 1 age class was predominant. The proportion of the matter production and storage increased with increasing patch radius. On the whole, young tillers and rhizomes had vigorous matter productivity and storage capacity. From the center to the edge of each patch, the matter production and storage were consistent with the trend of patch expansion, and the variation of tiller matter productivity and rhizome matter storage capacity was the biggest at the edge of each patch. The matter production and storage strategies of L. chinensis clonal population modules settled the matter basis for population expansion and progressive succession of community in the restoration succession process of flooded meadow.
{ "pile_set_name": "PubMed Abstracts" }
Activation of PPARgamma may mediate a portion of the anticancer activity of conjugated linoleic acid. A number of human cancer cell lines express the PPARgamma transcription factor, and agonists for PPARgamma are reported to promote apoptosis in these cell lines and impede their clonal expansion both in vitro and in vivo. Conjugated linoleic acid (CLA) can activate PPARgamma in rat adipocytes, possibly explaining CLA's antidiabetic effects in Zucker fatty rats. It is thus reasonable to suspect that a portion of CLA's broad spectrum anticarcinogenic activity is mediated by PPARgamma activation in susceptible tumors.
{ "pile_set_name": "PubMed Abstracts" }
Orbital Analysis and Excited-State Calculations in an Energy-Based Fragmentation Method. Covalently bound molecular arrays composed of porphyrins or related pigments have gained a lot of interest as components of artificial light-harvesting systems and molecular photonic devices. The large size of these arrays, however, makes their theoretical investigation employing the ab initio or density functional methodologies difficult. Energy-based fragmentation methods (EBF) represent a set of conceptually simple approaches to theoretical investigation of large systems and were therefore chosen as a tool to study these systems. Here a new approach to EBF, EBF-MO, is introduced that enables one to obtain orbitals and orbital energies and to perform population analysis and excited-state calculations of large systems composed of hundreds of atoms. This approach was implemented into a parallel program, JETT, and the benchmark calculations have shown its accuracy and applicability to the ground- and excited-state calculations of systems containing transition metals and extended π-conjugation. EBF-MO was then applied to the density functional theory (DFT) and the time-dependent density functional theory (TDDFT) calculations of ground- and excited-state properties of a porphyrin-based molecular photonic wire composed of 472 atoms and 4265 basis functions at the B3LYP/LANL08,6-31G* level. The TDDFT calculations have revealed the character of the excited states, and the unidirectionality of the excitation energy transfer across the array relevant to its signal transfer function. The computational approaches introduced here have widened the applicability of the ab initio and density functional methodologies to calculations of extended systems such as natural and artificial light-harvesting systems and molecular photonic devices.
{ "pile_set_name": "PubMed Abstracts" }
Combined effect of tumour necrosis factor-alpha and interleukin-13 polymorphisms on bronchial hyperresponsiveness in Korean children with asthma. TNF-alpha and IL-13, two pivotal pro-inflammatory cytokines, are increased in asthmatic airways and may be linked to asthma susceptibility and/or bronchial hyperresponsiveness (BHR). We investigated the association between the TNF-alpha-308G/A polymorphism and asthma susceptibility or asthma-related phenotypes in Korean children with asthma, and tested for a combined effect with IL-13 polymorphisms. Asthmatic children (n=719) and non-atopic healthy control children (n=243) were evaluated for asthma phenotypes including total serum IgE and BHR to methacholine. Genotypes were determined by PCR-restriction fragment length polymorphism analysis. The allele frequency of TNF-alpha-308A in asthmatics (14.1%) was higher than that in control children [8.7%, odds ratio (OR) 1.72, 95% confidence interval (CI) 1.05-2.82]. Significantly lower PC(20) values were found in asthmatic children carrying one or two copies of the TNF-alpha risk allele (-308A) vs. those homozygous for the common allele (P=0.026). Combined analysis revealed that atopic asthmatic children co-inherited the risk alleles of TNF-alpha-308G/A and IL-13 +2044G/A more frequently than control children (aOR 1.91, 95% CI 1.00-3.65), and asthmatic children co-inheriting both risk alleles had significantly lower PC(20) values vs. asthmatic children homozygous for the common alleles (P=0.024). The TNF-alpha promoter polymorphism (-308G/A) may be associated with asthma susceptibility and BHR in Korean children with asthma. In addition, there appears to be a synergistic effect between the TNF-alpha promoter polymorphism and an IL-13 coding region polymorphism in terms of asthma susceptibility and BHR in this population.
{ "pile_set_name": "PubMed Abstracts" }
Two cases of feline malignant craniopharyngioma. Tumors at the cranial base in 2 cats (a 9 1/2-year-old, castrated male Chinchilla and a 7-year-old, castrated male American Shorthair) were diagnosed as malignant craniopharyngioma. The tumor lesion was histopathologically divided into four parts: 1) a small acinus part, in which relatively large cells with a pale cytoplasm composed small acini; 2) a duct part, in which small cuboidal cells composed ducts; 3) a cyst part, in which there were large cysts lined with flat cells; and 4) a pavement part, in which large multi-angular-shaped cells proliferated in a pavement pattern. The epithelial cells of some parts were positive for keratin by immunohistochemistry. Histopathologic findings of the present feline cases were identical to those of malignant craniopharyngioma in other animal species.
{ "pile_set_name": "PubMed Abstracts" }
Development of a biodosimeter for radiation triage using novel blood protein biomarker panels in humans and non-human primates. In a significant nuclear event, hundreds of thousands of individuals will require rapid triage for absorbed radiation to ensure effective medical treatment and efficient use of medical resources. We are developing a rapid screening method to assess whether an individual received an absorbed dose of ≥2 Gy based on the analysis of a specific panel of blood proteins in a fingerstick blood sample. We studied a data set of 1051 human blood samples obtained from radiotherapy patients, normal healthy individuals, and several special population groups. We compared the findings in humans with those from irradiation studies in non-human primates (NHPs). We identified a panel of three protein biomarkers, salivary alpha amylase (AMY1), Flt3 ligand (FLT3L), and monocyte chemotactic protein 1 (MCP1), which are upregulated in human patients receiving fractionated doses of total body irradiation (TBI) therapy as a treatment for cancer. These proteins exhibited a similar radiation response in NHPs after single acute or fractionated doses of ionizing radiation. Our work provides confidence in this biomarker panel for biodosimetry triage using fingerstick blood samples and in the use of NHPs as a model for irradiated humans.
{ "pile_set_name": "PubMed Abstracts" }
Biomarkers to detect Wilms tumors in pediatric patients: where are we now? Wilms tumor (WT) is the most common pediatric renal tumor. Survival rates are high, whether treated according to the European protocols (SIOP-RTSG) that use prenephrectomy chemotherapy or the Children's Oncology Group (COG) protocols, with immediate nephrectomy. However, the more intensive treatment given to higher risk subgroups may result in late effects. Current risk stratification does not identify all tumors that relapse and loss of heterozygosity of 16q and 1p are the only molecular biomarkers used in risk stratification. In this review we describe recent new genetic and epigenetic findings in WT and discuss their potential use as biomarkers. We discuss approaches to ensure representative sampling of WTs including the potential for 'liquid biopsy' to circumvent intratumoral heterogeneity.
{ "pile_set_name": "PubMed Abstracts" }
Medication beliefs and adherence to antidepressants in primary care. The aim of this study was to determine whether patient beliefs about the necessity and concerns about medication were associated with adherence among those presenting with depression in primary care. At the end of a routine consultation with their general medical practitioner, patients completed questionnaires including measures of beliefs about medication, self reported adherence, depression severity, and demographic information. A significant relationship between beliefs in the necessity of antidepressants and adherence was not found. However, patient concerns with medications were positively associated with non-adherence. Where beliefs about the necessity outweighed concerns about taking the medication, significantly greater adherence was observed. Fewer depressive symptoms were also associated with greater adherence. This study extended prior research on the role of patient beliefs in medication adherence for chronic physical health problems by showing the belief-adherence relationship in a depressed patient sample. A balance between beliefs about the costs and benefits of medication are likely to be important in understanding adherence with other medications.
{ "pile_set_name": "PubMed Abstracts" }
Analysis time and lactation stage influence on lactoperoxidase system components in dairy ewe milk. To study the effect of time elapsed from the moment of taking samples on lactoperoxidase system components, we analyzed the activity of the lactoperoxidase enzyme and the concentrations of thiocyanate and hydrogen peroxide in 46 individual samples of Manchega ewe milk. Samples were maintained at a temperature of 4 degrees C until analysis, which took place at 6, 12, 24, and 48 h after extraction. Decreases were observed in lactoperoxidase activity when the analyses were performed at 48 h and in the thiocyanate and hydrogen peroxide concentrations at 12 h compared with those carried out earlier. Consequently, when the components of the lactoperoxidase system or its antibacterial activity are studied, the time elapsed since the sampling commenced must be taken into account. Similarly, the time elapsed is important when carrying out bacterial counts or residue screening by microbiological methods, during which the lactoperoxidase system may interfere. To study the component changes in the lactoperoxidase system during lactation, samples obtained 15, 30, 45, 60, 75, 90, 105, 120, and 135 d postpartum from 48 Manchega ewes were used. Average lactoperoxidase activity, thiocyanate, and hydrogen peroxide concentrations were 3.46 U/ml, 6.89 mg/L, and 0.39 mg/L, respectively, with significant variations throughout lactation. The thiocyanate and hydrogen peroxide levels at different lactation stages seemed to be insufficient to activate the lactoperoxidase system. Nevertheless, this could be achieved by adding 5 mg/L of thiocyanate and 8 mg/L of hydrogen peroxide at any time during lactation.
{ "pile_set_name": "PubMed Abstracts" }
The long road of biopharmaceutical drug development: from inception to marketing. The development of therapeutics is costly, time-consuming and has high attrition rates. Biopharmaceutical medications differ from traditional agents in their discovery, design, structure and formulation. Prior to marketing a drug must show efficacy and acceptable toxicity in both preclinical and clinical trials. Regulatory bodies have a pivotal role in the licensing, naming and marketing of an agent.
{ "pile_set_name": "PubMed Abstracts" }
Start-up evaluations and biocarriers transfer from a trickling filter to a moving bed bioreactor for synthetic mariculture wastewater treatment. Mariculture wastewater treatment by nitrification requires a long start-up time due to high salinity stress. This study aimed to verify the faster start-up of a trickling filter (TF) compared to a moving bed bioreactor (MBBR) treating synthetic mariculture wastewater, and to investigate the feasibility of transferring mature biocarriers from the TF to a new MBBR (TF-MBBR). The nitrogen removal performance, biofilm physicochemical properties and microbial communities were investigated. The results obtained showed that, the TF started up 41 days faster than the MBBR, despite the richer microbial diversity in the latter. Lower biofilm roughness and protein content as well as higher adhesive force and polysaccharide content in the TF were obtained compared to the MBBR. Adhesive force was found to be negatively correlated with roughness (r = -0.630, p = 0.069). Transmittance assigned to amide II (1538 cm-1) and amid III (1243 cm-1) through Fourier transform infrared spectroscopy (FTIR) determination was only obtained in the TF, which was likely related to the faster start-up. Nitrosomonas and Nitrospira were detected as the predominant nitrifiers in both reactors. In addition, the new MBBR, incubated with the mature biocarriers transferred from the TF, had a satisfactory nitrification performance with no lag time. Interestingly, the transfer action increased the microbial diversity and made the biofilm physicochemical characteristics shift toward those of the MBBR. Taken together, the study confirmed that MBBR nitrification start-up can be accelerated via TF and biocarrier transfer.
{ "pile_set_name": "PubMed Abstracts" }
Meeting Youth Where They Are: Substance Use Disorder Treatment in Schools. Providing school-based mental health treatment offers an opportunity to reach a greater number of affected youth by providing services in the setting where youth spend the majority of their time. In some contexts, even a single session of assessment has been linked with significant decreases in substance use; however, more robust treatments are likely needed to sustain these decreases over time. Empirically based individual and group treatments designed for delivery in clinic settings can readily be adapted for implementation in school settings. School-based delivery of substance use services offers an important opportunity to bridge a significant gap in services.
{ "pile_set_name": "PubMed Abstracts" }
New dihexadecyldithiophosphate SAMs on gold provide insight into the unusual dependence of adsorbate chelation on substrate morphology in SAMs of dialkyldithiophosphinic acids. We report the formation and characterization of new self-assembled monolayers (SAMs) formed from dihexadecyldithiophosphate (C16)2DDP and compare their properties with those of SAMs formed from the structurally similar adsorbate dihexadecyldithiophosphinic acid (C16)2DTPA. The new (C16)2DDP SAMs were characterized using X-ray photoelectron spectroscopy, reflection-absorption infrared spectroscopy, contact angle measurements, and electrochemical impedance spectroscopy. The data indicate that (C16)2DDP forms SAMs on gold films formed by e-beam evaporation in which all adsorbates chelate to gold, in contrast to (C16)2DTPA SAMs, in which 40% of the adsorbates are monodentate. The alkyl chains of the (C16)2DDP SAM are also less densely packed and ordered than those of the (C16)2DTPA SAM. To understand these differences, we present density functional theory calculations that show that there are only minimal differences between the geometric and electronic structures of the two adsorbates and that the energetic difference between monodentate and bidentate binding of a gold(I) ion are surprisingly small for both adsorbates. This study leads to the conclusion that differences in intermolecular interactions within the SAM are the driving force for the difference in chelation between the two adsorbates.
{ "pile_set_name": "PubMed Abstracts" }
Diaphragm myoclonus followed by generalised atonia in a patient with trisomy 4p: unusual semiology in an unusual condition. In this report, we describe a female patient with trisomy 4p, a rare genetic condition, with unusual seizure semiology. The patient is one of the oldest reported survivors with this condition. This semiology was noted while she was being monitored by inpatient video telemetry. We observed a series of myoclonic shoulder jerks, followed by hiccup-like episodes, and finally an atonic head drop. Corresponding ictal EEG showed semi-rhythmic high-amplitude slow waves with spikes superimposed over the frontotemporal areas. This semiology was confirmed as habitual by her parents. Subsequent hiccup-like episodes had no EEG correlate, and the head drop was again associated with semi-rhythmic high-amplitude slow waves and superimposed spikes, more prominent over the right hemisphere. In addition, we review the several cases in which hiccups have been associated with seizures and how this may relate to the neural pathways involved in the pathophysiology of hiccups. We believe the ictal hiccup-like episodes followed by atonia to be a seizure semiology that has not previously been documented. [Published with video sequence].
{ "pile_set_name": "PubMed Abstracts" }
Chemistry of odortypes in mice: Fractionation and bioassay. Mice can discriminate samples of urine obtained from two groups of inbred mice that are genetically identical except in their major histocompatibility complex (MHC) haplotype (congenic mice), whereas they cannot distinguish urine samples from two genetically identical groups of mice. Chemical fractions of urine samples obtained from MHC congenic mice were tested in a Y-maze olfactometer using a method modified to accommodate the bioassay to chemical fractions that might differ in sensory properties from the unfractionated urine. Fractions depleted in protein by several methods were consistently discriminable by mice in the Y maze, providing a direct demonstration that the airborne MHC genotype information can be conveyed by volatile compounds alone.
{ "pile_set_name": "PubMed Abstracts" }
[Clinical target volume : Principles and limits]. The clinical target volume (CTV) is regarded fundamental for radiotherapy planning by the International Commission on Radiation Units and Measurements (ICRU). The aim of this article is to give an overview on the basics and problems of defining the CTV for radiotherapy planning. After briefly defining CTV, a short description of the process to homogenize CTV in intraindividual comparisons is given, where special attention is paid to radiological requirements. This information is summarized in a number of tables. CTV is the most complex volume among the target volumes that have been defined by the ICRU. A survey of the determinants of the definition of CTV is given. This overview on the basic rules of how to define CTVs can help to increase the understanding of the radiological requirements for optimum imaging to support radiotherapy planning regardless of the specialty of the physician.
{ "pile_set_name": "PubMed Abstracts" }
Decreased NKG2D expression on NK cells correlates with impaired NK cell function in patients with gastric cancer. Although malignant diseases are known to be associated with immune suppression, the detailed mechanisms involved are still unknown. NKG2D is an activating cell surface receptor expressed by natural killer (NK) cells and CD8+ T cells, and the engagement of NKG2D is extremely important for NK cell activation. Although decreased NKG2D expression on NK cells is closely related to immune evasion by some cancers, the immunopathological importance of this phenomenon in gastric cancer patients remains unclear. NKG2D expression on NK cells was determined, using multicolor flow cytometry, to investigate the mechanisms responsible for immune evasion in gastric cancer patients. NKG2D expression on NK cells from gastric cancer patients was significantly lower than that in healthy controls. Also, NKG2D expression in advanced gastric cancer was significantly lower than that in early gastric cancer. NK cells from patients with lymph node metastasis expressed significantly lower levels of NKG2D than the NK cells from those without lymph node metastasis, and NKG2D expression on NK cells in gastric cancer tissue was significantly lower than that of circulating NK cells. NKG2D expression on NK cells obtained from cancer patients was restored after 48 h in culture with RPMI containing 10% AB serum. Furthermore, NKG2D expression on NK cells obtained after surgery was significantly higher than that before surgery. Decreased NKG2D expression on NK cells may be one of the key mechanisms responsible for NK cell dysfunction in gastric cancer.
{ "pile_set_name": "PubMed Abstracts" }
Sun awareness and behaviour in healthcare professionals and the general public. The knowledge, attitudes and behaviour of healthcare professionals and the general public towards issues of sun awareness were assessed in this questionnaire-based study. The findings indicated that junior doctors and nurses were no different from the general public when it came to seeking a tan or experiencing sunburn. The increased level of knowledge in doctors was not sufficient to have changed their behaviour and the medical profession should be targeted in education campaigns at an early stage in career development.
{ "pile_set_name": "PubMed Abstracts" }
Different spatio-temporal electroencephalography features drive the successful decoding of binaural and monaural cues for sound localization. The human ability to localize sound is essential for monitoring our environment and helps us to analyse complex auditory scenes. Although the acoustic cues mediating sound localization have been established, it remains unknown how these cues are represented in human cortex. In particular, it is still a point of contention whether binaural and monaural cues are processed by the same or distinct cortical networks. In this study, participants listened to a sequence of auditory stimuli from different spatial locations while we recorded their neural activity using electroencephalography (EEG). The stimuli were presented over a loudspeaker array, which allowed us to deliver realistic, free-field stimuli in both the horizontal and vertical planes. Using a multivariate classification approach, we showed that it is possible to decode sound source location from scalp-recorded EEG. Robust and consistent decoding was shown for stimuli that provide binaural cues (i.e. Left vs. Right stimuli). Decoding location when only monaural cues were available (i.e. Front vs. Rear and elevational stimuli) was successful for a subset of subjects and showed less consistency. Notably, the spatio-temporal pattern of EEG features that facilitated decoding differed based on the availability of binaural and monaural cues. In particular, we identified neural processing of binaural cues at around 120 ms post-stimulus and found that monaural cues are processed later between 150 and 200 ms. Furthermore, different spatial activation patterns emerged for binaural and monaural cue processing. These spatio-temporal dissimilarities suggest the involvement of separate cortical mechanisms in monaural and binaural acoustic cue processing.
{ "pile_set_name": "PubMed Abstracts" }
Hydrogen sulfide prevents homocysteine‑induced endoplasmic reticulum stress in PC12 cells by upregulating SIRT‑1. It was previously confirmed that hydrogen sulfide (H2S) has a neuroprotective effect, preventing homocysteine‑induced neurotoxicity. However, the exact molecular mechanisms underlying this protective effect remain to be fully elucidated. Endoplasmic reticulum (ER) stress contributes to homocysteine‑induced neurotoxicity. Silent mating type information regulator 2 homolog 1 (SIRT‑1) can attenuate ER stress, exerting its neuroprotective effect. Therefore, the present study aimed to investigate whether H2S protects PC12 cells against homocysteine‑induced ER stress and whether SIRT‑1 mediates this protective effect of H2S. Western blotting was used to detect the expression of SIRT‑1, glucose‑regulated protein 78 (GRP78), and cleaved caspase‑12 in PC12 cells. It was observed that sodium hydrosulfide (NaHS), an exogenous H2S donor, significantly attenuated the homocysteine‑induced ER stress responses, including increases in the protein expression levels of GRP78 and cleaved caspase‑12. Simultaneously, NaHS upregulated the expression of SIRT‑1 and reversed the homocysteine‑induced downregulation of SIRT‑1 in PC12 cells. Sirtinol, a specific inhibitor of SIRT‑1, eliminated the protective effects of H2S in homocysteine‑induced ER stress. These data indicated that H2S prevented homocysteine‑induced ER stress via enhancing the expression of SIRT‑1. These findings offer novel insight into the protective mechanisms of H2S against homocysteine‑induced neurotoxicity.
{ "pile_set_name": "PubMed Abstracts" }
Control of Q-switched mode locking by active feedback. It is demonstrated that Q-switching dynamics in mode-locked lasers can be controlled by use of an active feedback loop. Analytic design rules for the feedback loop are presented. Suppression of Q-switched mode locking in a diode-pumped, passively mode-locked Nd:YVO(4) laser is shown experimentally and numerically.
{ "pile_set_name": "PubMed Abstracts" }
[Gingival hyperplasia during treatment with nifedipine]. Nifedipine is a relatively new and increasingly used medication for treatment of all kinds of angina pectoris and arterial hypertension. The principal action of nifedipine is to inhibit the influx of extracellular calcium ions across the membranes of cardiac and vascular smooth muscle cells, without changing serum calcium concentration (1). One of the side effects of this drug is gingival hyperplasia which was first described in 1984 by Lederman (2). He noted that gingival hyperplasia is mostly marked on the labial gingiva of the upper and lower anterior teeth and appeared 1 to 2 months after nifedipine therapy began at a dose of 90 mg per day, and never occurs in edentulous areas. This paper reports gingival hyperplasia in a patient treated with nifedipine. A 73-year-old man referred to the dental clinic for evaluation of gingival enlargement in the maxillar left quadrant which he had noticed about 3 months after starting the nifedipine therapy. Clinical examination showed gingival enlargement around the teeth 22, 23, 24 and 27, but with normal edentulous area (Fig. 1). The enlarged gingiva was red, smooth and shiny, with no pain on touch, and bled easily on probing. There were metal crowns with overhanging margins and pseudopockets--6 mm with dental plaque and calculus. Radiographs showed moderate alveolar bone resorption of horizontal type. The patient's maxillar left first premolar exhibited severe bone loss, resulting in a hopeless prognosis. This tooth was extracted under local anesthesia. The dental treatment included replacement of the ill-fitting metal crowns, scaling and root planning, and instructions on appropriate method for brushing teeth. 6 weeks later, the hyperplastic tissues were removed surgically. In a 1-year follow-up period, the patient was recalled at regular intervals for control, and no signs of recurrence of gingival hyperplasia have been observed in spite of continued nifedipine treatment. Biopsies taken from the gingivectomy specimens were handled with standard histological method. Histological examination showed a thick epithelium with parakeratosis and acanthosis, and irregular elongation of the rete peg. The underlying connective tissues contained dense fibers with inflammatory cell infiltrate mainly composed of plasma cells. The exact mechanism of action of nifedipine in causing gingival enlargement is unknown at present. There is also no answer to the question why gingival enlargement appears in some patients treated with nifedipine, but in others not. The clinical findings (3, 4, 5, 6, 7) and results of in vitro study (8) and this case report showed that hyperplastic change of gingiva started only in areas displaying signs of inflammation, but not in healthy and edentulous areas. These observations suggest that local factors and associated inflammation is essential for onset of the nifedipine-induced gingival hyperplasa. Moreover, it was suggested that duration of nifedipine therapy (more than 2 months) and drug dosage (90 mg per day) could be important (1,2,3). This case report also demonstrates that no signs of recurrence of hyperplasia were observed after elimination of the local inflammatory factors: extensive dental pluque control and surgical removal of the hyperplastic gingival tissue even though administration of nifedipine was continued. It was concluded that gingival enlargement occurs in patients with nifedipine therapy only in the areas where local inflammatory factors are present.
{ "pile_set_name": "PubMed Abstracts" }
Surgical observations on the endolymphatic sac in Meniere's disease. This study aimed to clarify the pathoanatomic characteristics of the endolymphatic sac in Meniere's disease by surgical observations. The study design was a retrospective case study conducted in the setting of University Hospital at Shiga University of Medical Science. Studied were 101 patients with Meniere's disease who underwent endolymphatic sac drainage surgery at the university hospital by the same surgical team between 1984 and 1995. Control group consisted of 23 patients with non-Meniere's disease. Photographs were taken of the sac in 101 patients with Meniere's disease during endolymphatic sac drainage surgery, and the pathoanatomic findings of the sacs were classified into three grades regarding position (types I, II, III), size (large, intermediate, small), color (red, intermediate, white), and vascularity (fair, intermediate, poor). Statistical difference was studied between Meniere's group and non-Meniere's group by chi-square test. The patients with Meniere's disease were found to have endolymphatic sacs located inferiorly to the posterior semicircular canal, very close to the jugular bulb (type III) (p < 0.001). The sacs also were smaller in size (p = 0.068), whiter in surface color (p = 0.0036, 0.01), and of less vascularity (p = 0.051) than those of the patients with non-Meniere's disease. The comparisons showed significant differences only in position and color. The patients with Meniere's disease were found to have endolymphatic sacs located inferiorly to the posterior semicircular canal, very close to the jugular bulb. The sacs also were whiter in surface color.
{ "pile_set_name": "PubMed Abstracts" }
[Interaction of work demands in the genesis of mental suffering]. Current working conditions and new forms of work organization are affecting workers' health in numerous ways which can only be explained by more complex theories and methodologies than those used traditionally. The authors analyze some important elements of the work process and the interaction among work demands as determinants of mental and psychosomatic disorders and fatigue (MPDF) among workers in a Mexican industrial plant. The workers studied (n = 830) were male, with a mean age of 32. MPDF represent one-third of the disease burden among these workers. An association was observed with the number of years worked, type of activity, and job area. Job-related demands and work organization, including excessive work, strict supervision, dangerous work, unnatural positions, and intense and hard physical labor were also closely related to these conditions. The most relevant problem is the combination of many different demands. Interaction among the combinations was found to be additive or synergistic. In the latter condition the risk of morbid effects increases beyond merely an additive effect.
{ "pile_set_name": "PubMed Abstracts" }
Metabolism of toad ventricle during alterations to the inotropic state. The heat produced by toad ventricle during manipulations of the inotropic state was measured using thermopiles, and some comparisons made to rat ventricle. The tension-independent heat, peak stress, and the tension-dependent heat increased when [Ca2+]o increased from 0.25 to 2 mM in Ringer. In 2 mM [Ca2+]o, tension-independent heat, peak stress, and tension-dependent heat were 3.1 +/- 0.4 mJ/g, 38.4 +/- 5.5 mN/mm2, and 0.49 +/- 0.06 units; about 25% of the tension-independent heat may relate to the Na(+)-K+ pump. At similar [Ca2+]o, rat ventricle produced a smaller tension-independent heat (1.6 +/- 0.2 mJ/g), and active heat per unit stress (0.22 +/- 0.01 units) than toad. Tension-independent heat, stress, and tension-dependent heat were increased by orciprenaline, and decreased by BDM. Ouabain increased the stress and tension-dependent heat but not the tension-independent heat. Five millimolar [Ca2+]o in HEPES buffer decreased the stress but increased the tension-dependent heat compared to 2 mM [Ca2+]o in Ringer. Ryanodine and CPA caused major reductions in force and tension-independent heat in rat, but had little effect on toad ventricle. In conclusion, our results suggest that in toad ventricle (a) the sarcoplasmic reticulum plays only a minor role in activation and relaxation, (b) the Na(+)-K+ pump contributes substantially to activation metabolism, (c) active metabolism is stimulated by increases in [Ca2+]o and (d) there is a larger tension-independent heat, a larger active metabolism per unit stress, and a lower basal metabolism than in rat papillary muscle. The energy cost of removing intracellular Ca2+ through the sarcolemma appears to be greater than uptake into sarcoplasmic reticulum.
{ "pile_set_name": "PubMed Abstracts" }
Ultrasonography of the hip in preterm neonates. Over the period of one year, the hips of 92 preterm neonates were examined by ultrasound. Using the Graf classification only 7% showed an angle alpha between 50 and 60 degrees, which is characteristic of type IIa hips. In all other cases the angle alpha was above 60 degrees (type I). Sonographically there were no pathological cases (type IIg or worse). A reason for the relatively low number of type IIa hips could be that the short osseous acetabular rim and the broad cartilagenous Y-joint in this age group result in a "false" increase of the angle alpha.
{ "pile_set_name": "PubMed Abstracts" }
Alpha-hydroxybutyrate dehydrogenase as a biomarker for predicting systemic lupus erythematosus with liver injury. To explore potential biomarkers for identifying systemic lupus erythematosus (SLE) with liver injury. This retrospective study examined the records of 158 SLE cases. The Apriori algorithm of association rules was employed to identify laboratory indexes related to liver injury in SLE patients. The ratio of albumin to globulin; levels of alpha-hydroxybutyrate dehydrogenase (α-HBDH), calcium, hemoglobin, urine protein, total cholesterol; absolute value of lymphocytes; red cell distribution width and hematocrit were identified by the Apriori algorithm from SLE-related liver injury patients. α-HBDH was identified as an independent risk factor for SLE-related liver injury. There were more SLE patients with liver injury in high-α-HBDH group than in low-α-HBDH group (64.63% vs. 21.05%; P < 0.001). In high-α-HBDH group, levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and gamma-glutamyl transpeptidase (GGT), and the AST/ALT ratio were significantly higher, and albumin and complement 3 (C3) were markedly lower. Moreover, α-HBDH level was significantly higher in the SLE-related liver injury patients than in the non-SLE-related liver injury patients. In addition, α-HBDH was positively correlated with levels of AST and LDH, the AST/ALT ratio, and the SLE Disease Activity Index 2000, and it was negatively correlated with albumin and C3. The optimal cutoff value of α-HBDH for distinguishing SLE patients with and without liver injury was 258.50 U/L, which provided a 60.94% sensitivity and a 94.67% specificity. α-HBDH could be used to evaluate the disease activity of SLE-related liver injury, and it may be a potential biomarker for diagnosing SLE-related liver injury.
{ "pile_set_name": "PubMed Abstracts" }
Intestinal parasites in Cambodians: comparison of diagnostic methods used in screening refugees with implications for treatment of populations with high rates of infestation. We performed a retrospective review of screening parasitology examinations on a Cambodian refugee population served by an urban neighborhood health center. Five-hundred twenty of 1084 patients were examined for ova and parasites either by purged stool, which was examined immediately, or preserved stool, examined at a teaching hospital and proprietary laboratories. Overall, 335 (64 percent) of the tested patients had at least one parasite. The prevalence of infection varied by test technique (purged stool examined immediately, 86 percent; preserved stool examined at a hospital, 65 percent; preserved stool sent to a proprietary laboratory, 31 percent, P less than 0.01). In this population where Entamoeba histolytica infection was 44 percent as measured by the purged warm stool technique, the cold preserved stool test had a measured relative sensitivity of 33 percent. Assuming a selectivity of 99 percent, it would take eight negative tests to reach a greater than 95 percent negative predictive value. The high rate of intestinal carriage of pathogenic parasites in this population and the insensitivity of commonly available diagnostic tests make routine presumptive treatment of intestinal parasites an option when the purged stool examination is unavailable.
{ "pile_set_name": "PubMed Abstracts" }
Differential affinities of visual arrestin, beta arrestin1, and beta arrestin2 for G protein-coupled receptors delineate two major classes of receptors. Visual arrestin, betaarrestin1, and betaarrestin2 comprise a family of intracellular proteins that desensitize G protein-coupled receptors (GPCRs). In addition, betaarrestin1 and betaarrestin2 target desensitized receptors to clathrin-coated pits for endocytosis. Whether arrestins differ in their ability to interact with GPCRs in cells is not known. In this study, we visualize the interaction of arrestin family members with GPCRs in real time and in live cells using green fluorescent protein-tagged arrestins. In the absence of agonist, visual arrestin and betaarrestin1 were found in both the cytoplasm and nucleus of HEK-293 cells, whereas betaarrestin2 was found only in the cytoplasm. Analysis of agonist-mediated arrestin translocation to multiple GPCRs identified two major classes of receptors. Class A receptors (beta2 adrenergic receptor, mu opioid receptor, endothelin type A receptor, dopamine D1A receptor, and alpha1b adrenergic receptor) bound betaarrestin2 with higher affinity than betaarrestin1 and did not interact with visual arrestin. In contrast, class B receptors (angiotensin II type 1A receptor, neurotensin receptor 1, vasopressin V2 receptor, thyrotropin-releasing hormone receptor, and substance P receptor) bound both betaarrestin isoforms with similar high affinities and also interacted with visual arrestin. Switching the carboxyl-terminal tails of class A and class B receptors completely reversed the affinity of each receptor for the visual and non-visual arrestins. In addition, exchanging the betaarrestin1 and betaarrestin2 carboxyl termini reversed their extent of binding to class A receptors as well as their subcellular distribution. These results reveal for the first time marked differences in the ability of arrestin family members to bind GPCRs at the plasma membrane. Moreover, they show that visual arrestin can interact in cells with GPCRs other than rhodopsin. These findings suggest that GPCR signaling may be differentially regulated depending on the cellular complement of arrestin isoforms and the ability of arrestins to interact with other cellular proteins.
{ "pile_set_name": "PubMed Abstracts" }
[Expression of WNK4 gene regulated by aldosterone]. To study the expression and mechanism of WNK4 gene regulated by aldosterone. Wistar rats were treated with aldosterone and potassium water. Serum aldosterone and ion as well as urine ion were measured. The expression of WNK4 gene in kidney tissues was detected by real-time PCR. Kidney-derived HEK293 cells were cultured, transfected with pGL3-WNK4, and then stimulated by aldosterone. After 24 h of transfection, luciferase activities of the plasmid were detected. Compared with those of the controls, serum aldosterone and urine K(+) of experimental rats were significantly elevated, whilst urine Na(+) was significantly decreased. And urine Cl(-) was significantly increased only in the group of high K(+). Serum K(+), Na(+) and Cl(-) showed no significant difference. Expression of WNK4 gene in kidney tissues was significantly decreased. The luciferase activity of pGL3-WNK4-484 plasmid has decreased after stimulated with aldosterone, while the activity of pGL3-WNK4-275 showed no change. Aldosterone can down-regulate the expression of WNK4 through binding with regulatory element in the upstream of the gene.
{ "pile_set_name": "PubMed Abstracts" }
How feasible is the life expectancy target in the Saudi Arabian vision for 2030? Over the period 2016-2030, Saudi Arabia seeks to increase life expectancy at birth by 6 years. The main aim was to analyse the feasibility of this gain using the demographic literature. The demographic literature on recorded high gains in life expectancy and the determinants of these gains were reviewed. The findings were examined considering the Saudi Arabian context. Explanations covered demographic and behavioural factors, inequalities, health care delivery system, public health provision, health-related policies and advancements in science and technology. However, the crucial factor is the country's position in the "cardiovascular revolution" (which combines smoking prevalence, obesity, lifestyle and related policies). In countries where life expectancy is in the 70s, average yearly gains are less than 0.31 years, much lower that the Saudi Arabian target of 0.43 years. For Saudi Arabia, an average yearly gain of about half this is achievable provided the fundamental drivers of life expectancy are addressed.
{ "pile_set_name": "PubMed Abstracts" }
The evolution of P2X7 antagonists with a focus on CNS indications. The P2X7 receptor is an ATP-gated nonselective cation channel that has been linked to a number of inflammatory diseases. Activation of the P2X7 receptor by elevated levels of ATP results in the release of proinflammatory cytokines and elevated levels of these cytokines has been associated with a variety of disease states. A number of research groups in both industry and academia have explored the identification of P2X7R antagonists as therapeutic agents. Much of this early effort focused on the treatment of diseases related to peripheral inflammation and resulted in several clinical candidates, none of which were advanced to market. The emerging role of the P2X7 receptor in neuroinflammation and related diseases has resulted in a shift in medicinal chemistry efforts toward the development of centrally penetrant antagonists. This review will highlight the biology supporting the role of P2X7 in diseases related to neuroinflammation and review the recent medicinal chemistry efforts to identify centrally penetrant antagonists.
{ "pile_set_name": "PubMed Abstracts" }
Expression of Hes6 and NeuroD in the olfactory epithelium, vomeronasal organ and non-sensory patches. Basic helix-loop-helix transcription factors NeuroD and Hes6 promote neuronal differentiation. The expression of their genes in the olfactory epithelium (OE), vomeronasal organ (VNO) and the non-sensory patches of the posterior nasal cavity of mice was examined. As detected by in situ hybridization, Hes6 was expressed in a basal progenitor layer of the embryonic OE. After birth, the expression of Hes6 was detected in a cell layer above the basement membrane, globose basal cells (GBCs). Expression of NeuroD in the embryonic OE was in agreement with that previously described; and in the postnatal OE, it was detected in cells of GBC layer and cells upper to GBCs. In the VNO, Hes6 was expressed throughout the sensory epithelium (S-VNO) at embryonic day 12, and later became restricted to a single layer of cells in the basal region of the S-VNO, where Hes5-expressing undifferentiated cells were present. NeuroD was expressed throughout the S-VNO during the embryonic stage. After birth, Hes6 and NeuroD expressions were observed in the border between the S-VNO and non-sensory VNO. Immunohistochemistry using anti-NeuroD antibody revealed that NeuroD-positive cells were still present not only at the edges but also in the center of the S-VNO until P3. These findings suggest that Hes6 and NeuroD are expressed in progenitors of chemoreceptor neurons and that the expression of Hes6 precedes that of NEUROD: Moreover, in the regenerating VNO of bulbectomized mice, NeuroD-positive cells were observed both at the edges and in the center of the S-VNO, suggesting that neuronal turnover occurred in both regions. Moreover, in the dorsal fossa of the posterior nasal cavity, several non-sensory patches are formed between postnatal (P) days 10 and 21 because of programmed death of ORNs and GBCs. During embryonic stages, the expression of Hes6 and NeuroD in the OE showed no regional differences. At P3-P7, expression of NeuroD and Hes6 disappeared in the region corresponding to the presumptive non-sensory patches. The loss of these genes may stop the differentiation and may cause apoptosis of GBCs and ORNs.
{ "pile_set_name": "PubMed Abstracts" }