tbuckley/cabot-search huggingface dataset:
Glomerulopathy in rats with streptozotocin diabetes. Accumulation of glomerular basement membrane analogous to human diabetic nephropathy.
Authors: M P Cohen, C V Klein
Journal: The Journal of Experimental Medicine (1979)

Glomeruli from streptozotocin-diabetic and age-matched nondiabetic rats were quantitatively isolated by a differential sieving technique. The insoluble glomerular basement membranes were purified following sonic disruption in the presence of proteolytic inhibitors. The yield of glomeruli and of glomerular basement membrane relative to the amount of renal cortex and the body weight of the animals, as well as the calculated amount of basement membrane per glomerulus, were all significantly greater in diabetic rats when compared to non-diabetic controls. Glomerular basement membranes from normal and diabetic rats were solubilized by reduction and denaturation in the presence of SDS and subjected to agarose gel analysis. About 65% of both normal and diabetic basement membrane was solubilized by this procedure, and the elution profiles of non-diabetic and diabetic preparations were similar. These results suggest that rat renal basement membrane is qualitatively similar but quantitatively increased in streptozotocin-diabetes. Since glomerular enlargement and accumulation of basement membrane are characteristic of human diabetic nephropathy, the findings also suggest that the streptozotocin-diabetic rat is an appropriate animal model for studies relating to the pathogenesis of this complication of diabetes.
Sickle cell anemia and β‐gene cluster haplotypes in Cuba
Authors: A. Muniz, L. Corral, C. Alaez, E. Svarch, E. Espinosa, N. Carbonell, R. Di Leo, L. Felicetti, R. L. Nagel, G. Martinez
Journal: American Journal of Hematology (1995)

We have studied 91 patients with SS genotype, 44 children and 47 adults. Excluding the Cameroon and atypical haplotypes, the distribution in the children's sample exhibited 43% Benin, 38% Bantu, and 3% Senegal. In adults, the sample exhibited 46% Benin, 30% Bantu, and 9% Senegal (chi 2: 13.511, 2 df, P = 0.001). When the whole sample of 198 chromosomes (SS, SC, and S/beta thal) is considered, we find that the beta s chromosome is linked 51% to the Benin haplotype, 41% with the Bantu, and 8% with the Senegal. After adjusting for the different frequencies of beta s in Africa, these numbers would predict the port of origin to be 16% from Atlantic West Africa, 37.3% from Central West Africa, and 46% from Bantu-speaking Africa. This is in direct contradiction with the historical record that establishes a higher percentage from Bantu-speaking Africa (55%) and a much lower percentage from Senegal (3.4%). The overall conclusions from these findings is that there is a loss of Bantu haplotypes in sickle cell syndromes in Cuba, particularly among adults, and that there is an excess of Senegal haplotype, also among adults. These differences might reflect the differential survival and severity of the sickle cell disease linked to these haplotypes.
Gαq and Gα11 contribute to the maintenance of cellular electrophysiology and Ca2+ handling in ventricular cardiomyocytes
Authors: Sara Pahlavan, Martin Oberhofer, Benjamin Sauer, Sandra Ruppenthal, Qinghai Tian, Anke Scholz, Lars Kaestner, Peter Lipp
Journal: Cardiovascular Research (2012)

AimsGαq and Gα11 signalling pathways contribute to cardiac diseases such as hypertrophy and arrhythmia, but their role in cardiac myocytes from healthy hearts has remained unclear. We aimed to investigate the contribution of Gαq and Gα11 signalling to the basal properties of ventricular myocytes.
Fasting Insulin Level Is Positively Associated With Incidence of Hypertension Among American Young Adults
Authors: Pengcheng Xun, Kiang Liu, Wenhong Cao, Stephen Sidney, O. Dale Williams, Ka He
Journal: Diabetes Care (2012)

Although hyperinsulinemia, a surrogate of insulin resistance, may play a role in the pathogenesis of hypertension (HTN), the longitudinal association between fasting insulin level and HTN development is still controversial. We examined the relation between fasting insulin and incidence of HTN in a large prospective cohort.A prospective cohort of 3,413 Americans, aged 18-30 years, without HTN in 1985 (baseline) were enrolled. Six follow-ups were conducted in 1987, 1990, 1992, 1995, 2000, and 2005. Fasting insulin and glucose levels were assessed by a radioimmunoassay and hexokinase method, respectively. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs of incident HTN (defined as the initiation of antihypertensive medication, systolic blood pressure ≥140 mmHg, or diastolic blood pressure ≥90 mmHg).During the 20-year follow-up, 796 incident cases were identified. After adjustment for potential confounders, participants in the highest quartile of insulin levels had a significantly higher incidence of HTN (HR 1.85 [95% CI 1.42-2.40]; P(trend) < 0.001) compared with those in the lowest quartile. The positive association persisted in each sex/ethnicity/weight status subgroup. A similar dose-response relation was observed when insulin-to-glucose ratio or homeostatic model assessment of insulin resistance was used as exposure.Fasting serum insulin levels or hyperinsulinemia in young adulthood was positively associated with incidence of HTN later in life for both men and women, African Americans and Caucasians, and those with normal weight and overweight. Our findings suggested that fasting insulin ascertainment may help clinicians identify those at high risk of HTN.
Role of the Aggresome Pathway in Cancer: Targeting Histone Deacetylase 6–Dependent Protein Degradation
Authors: Agustin Rodriguez-Gonzalez, Tara Lin, Alan K. Ikeda, Tiffany Simms-Waldrip, Cecilia Fu, Kathleen M. Sakamoto
Journal: Cancer Research (2008)

Abstract Misfolded or aggregated proteins have two fates: they are either refolded with the help of chaperones or degraded by the proteasome. Cells also have an alternative pathway that involves intracellular “storage bins” for misfolded intracellular proteins known as aggresomes. Aggresomes recruit motor proteins that transport misfolded or aggregated proteins to chaperones and proteasomes for subsequent destruction. There is emerging evidence that inhibiting the aggresome pathway leads to accumulation of misfolded proteins and apoptosis in tumor cells through autophagy. We discuss the role of aggresomes in cancer and the potential to target this pathway for therapy. [Cancer Res 2008;68(8):2557–60]
The effect of cooling prior to and during exercise on exercise performance and capacity in the heat: a meta-analysis
Authors: Christopher James Tyler, Caroline Sunderland, Stephen S Cheung
Journal: British Journal of Sports Medicine (2013)

Exercise is impaired in hot, compared with moderate, conditions. The development of hyperthermia is strongly linked to the impairment and as a result various strategies have been investigated to combat this condition. This meta-analysis focused on the most popular strategy: cooling. Precooling has received the most attention but recently cooling applied during the bout of exercise has been investigated and both were reviewed. We conducted a literature search and retrieved 28 articles which investigated the effect of cooling administered either prior to (n=23) or during (n=5) an exercise test in hot (wet bulb globe temperature >26°C) conditions. Mean and weighted effect size (Cohen's d) were calculated. Overall, precooling has a moderate (d=0.73) effect on subsequent performance but the magnitude of the effect is dependent on the nature of the test. Sprint performance is impaired (d=-0.26) but intermittent performance and prolonged exercise are both improved following cooling (d=0.47 and d=1.91, respectively). Cooling during exercise has a positive effect on performance and capacity (d=0.76). Improvements were observed in studies with and without cooling-induced physiological alterations, and the literature supports the suggestion of a dose-response relationship among cooling, thermal strain and improvements in performance and capacity. In summary, precooling can improve subsequent intermittent and prolonged exercise performance and capacity in a hot environment but sprint performance is impaired. Cooling during exercise also has a positive effect on exercise performance and capacity in a hot environment.
In Vivo Modeling of Myosin Binding Protein C Familial Hypertrophic Cardiomyopathy
Authors: Qinglin Yang, Atsushi Sanbe, Hanna Osinska, Timothy E. Hewett, Raisa Klevitsky, Jeffrey Robbins
Journal: Circulation Research (1999)

Abstract —Myosin binding protein C (MyBP-C) is an integral part of the striated muscle sarcomere. As is the case for other sarcomeric genes in human populations, multiple mutations within the gene have been linked to familial hypertrophic cardiomyopathy. Although some MyBP-C lesions are the result of missense mutations, most show truncated polypeptides lacking either the myosin or myosin and titin binding sites. Previously, we generated transgenic (TG) mice with cardiac-specific expression of a MyBP-C mutant lacking the myosin and titin binding domains. Surprisingly, the mutant protein was stable and made up a majority of the MyBP-C species, with concomitant reductions in endogenous MyBP-C such that overall MyBP-C stoichiometry was conserved. In the present study, we created a second series of TG mice that express, in the heart, a mutant MyBP-C lacking only the myosin binding site. In contrast to the previous data for the MyBP-C lacking both titin and myosin binding sites, only very modest levels of protein were found, consistent with data obtained from human biopsies in which mutated MyBP-C could not be detected. Despite normal levels of wild-type MyBP-C, there were significant changes in the structure and ultrastructure of the heart. Fiber mechanics showed decreased unloading shortening velocity, maximum shortening velocity, and relative maximal power output.
D<scp>IFFERENT</scp> A<scp>PPROACHES TO</scp> D<scp>EFINE</scp> I<scp>NDIVIDUAL</scp> A<scp>MINO</scp> A<scp>CID</scp> R<scp>EQUIREMENTS</scp>
Authors: Paul B. Pencharz, Ronald O. Ball
Journal: Annual Review of Nutrition (2003)

A full review of the strengths and limitations of the various methods used to define amino acid requirements is provided. The focus is on the recent development of carbon oxidation techniques such as indicator amino acid oxidation and 24-h amino acid balance to determine dietary indispensable (essential) amino acid needs in adults. All approaches depend on the change in a metabolic parameter in response to graded intake of the test amino acid. In humans, the within-subject variance is less than the between-subject variance, which has led to an appreciation of the need to study each subject across a range of intakes, above and below the mean requirement level. The data can then be analyzed using two-phase linear regression crossover and a precise population mean requirement can be determined. Several approaches have been used to define the variance of the mean requirement. Finally, a minimally invasive indicator amino acid oxidation model has been developed which allows the determination of dietary essential amino acid requirements in children and other vulnerable populations.
Intravenous nitroglycerin in the treatment of spontaneous angina pectoris: a prospective, randomized trial.
Authors: G D Curfman, J A Heinsimer, E C Lozner, H L Fung
Journal: Circulation (1983)

A prospective, randomized study of i.v. nitroglycerin (TNG) in the management of repetitive spontaneous angina pectoris was undertaken in 40 consecutive patients. The clinical effectiveness of i.v. TNG (group A) was compared with that of oral isosorbide dinitrate (ISDN) and topical 2% nitroglycerin ointment (NO) in combination (group B) during a 72-hour treatment period. The doses of both nitrate regimens were adjusted so that the mean arterial pressure in the two groups was reduced by 15 +/- 3% of control values to the same level (77 mm Hg). The i.v. TNG dose of 10-200 micrograms/min yielded arterial plasma TNG levels of 1.2-65.3 ng/ml and estimated plasma (arterial) clearance of 106 +/- 55 ml/min/kg of body weight (mean +/- SD). In group B, the doses were 20-60 mg (oral ISDN) and 1/2-2 inches (NO) every 6 hours. Intravenous TNG reduced the number of spontaneous ischemic episodes from 3.3 +/- 0.8 per 24 hours during the control period to 1.0 +/- 0.3 per 24 hours during the treatment period (p less than 0.01), while the ISDN/NO combination reduced the number of episodes from 3.1 +/- 0.4 to 1.4 +/- 0.3 (p less than 0.01). Overall, the magnitude of the therapeutic effect of i.v. TNG was statistically indistinguishable from that of ISDN/NO, although i.v. TNG did have somewhat greater clinical benefit on day 2 of the 3-day treatment period. Furthermore, the data suggested more consistent control of ischemic episodes with i.v. TNG during the first 24 hours of the trial. Although both regimens markedly reduced the frequency of spontaneous ischemic episodes, only 36% of patients in group A and 17% in group B experienced no ischemic episodes during the study period (NS). Forty-three percent of patients in group A and 61% in group B (NS) required early coronary artery bypass surgery to control recurrent ischemic episodes refractory to medical therapy. We conclude that i.v. TNG and ISDN/NO, when administered in doses adjusted to produce similar effects on systemic arterial pressure, have nearly equivalent clinical effects in the management of patients with frequent episodes of spontaneous angina pectoris. Intravenous TNG offers the advantage of more consistent control of ischemic episodes during the first 24 hours of treatment. Nevertheless, the recurrence rate of spontaneous ischemic episodes during medical therapy is high with both regimens, and early coronary artery bypass surgery may be required for long-term management.
Diagnostic Tests in Allergy to Green Coffee
Authors: K. Osterman, S. G. O. Johanssons, O. Zetterström
Journal: Allergy (1985)

Twenty‐two coffee roastery workers with work‐related symptoms of various degree from the eyes, nose or bronchi were tested with partly purified water‐soluble extract from dust of green coffee beans (GCB). Eighteen persons had a positive prick test, eight a positive bronchial provocation test and seven a positive nasal provocation test. Fourteen had a positive methacholine test, indicating unspecific bronchial hyperreactivity. Specific IgE antibodies to GCB extract were found in sera of 11 workers and to castor bean (CB) extract in 16. The workers measured their lung function with an air flow meter, three times a day for 1 week, and the values were lower in the second half of the week for the workers with IgE antibodies to GCB, but not for the others. It is concluded that the case history, prick test, RAST, and simple lung function tests for one or a few weeks are the best tools when investigating occupational allergy. When the allergen is unknown, but the occurrence of an IgE‐mediated allergy is suspected, serial lung function measurements and determinations of total serum IgE, in addition to taking a careful case history, are valuable methods with which to start the investigation.
Resistance of rat hepatocytes against bile acid-induced apoptosis in cholestatic liver injury is due to nuclear factor-kappa B activation
Authors: Marieke H Schoemaker, Willemijn M Gommans, Laura Conde de la Rosa, Manon Homan, Pieter Klok, Christian Trautwein, Harry van Goor, Klaas Poelstra, Hidde J Haisma, Peter L.M Jansen, Han Moshage
Journal: Journal of Hepatology (2003)
Even a low-dose of moderate-to-vigorous physical activity reduces mortality by 22% in adults aged ≥60 years: a systematic review and meta-analysis
Authors: David Hupin, Frédéric Roche, Vincent Gremeaux, Jean-Claude Chatard, Mathieu Oriol, Jean-Michel Gaspoz, Jean-Claude Barthélémy, Pascal Edouard
Journal: British Journal of Sports Medicine (2015)

Background The health benefits of 150 min a week of moderate-to-vigorous-intensity physical activity (MVPA) in older adults, as currently recommended, are well established, but the suggested dose in older adults is often not reached. Objectives We aimed to determine whether a lower dose of MVPA was effective in reducing mortality, in participants older than 60 years. Methods The PubMed and Embase databases were searched from inception to February 2015. Only prospective cohorts were included. Risk ratios of death were established into four doses based on weekly Metabolic Equivalent of Task (MET)-minutes, defined as inactive (reference), low (1–499), medium (500–999) or high (≥1000). Data were pooled and analysed through a random effects model using comprehensive meta-analysis software. Results Of the 835 reports screened, nine cohort studies remained, totalling 122 417 participants, with a mean follow-up of 9.8±2.7 years and 18 122 reported deaths (14.8%). A low dose of MVPA resulted in a 22% reduction in mortality risk (RR=0.78 (95% CI 0.71 to 0.87) p&lt;0.0001). MVPA beyond this threshold brought further benefits, reaching a 28% reduction in all-cause mortality in older adults who followed the current recommendations (RR=0.72 (95% CI 0.65 to 0.80) p&lt;0.0001) and a 35% reduction beyond 1000 MET-min per week (RR=0.65 (95% CI 0.61 to 0.70) p&lt;0.0001). Conclusions A dose of MVPA below current recommendations reduced mortality by 22% in older adults. A further increase in physical activity dose improved these benefits in a linear fashion. Older adults should be encouraged to include even low doses of MVPA in their daily lives.
Thalamic high-grade gliomas in children: a distinct clinical subset?
Authors: C. M. Kramm, S. Butenhoff, U. Rausche, M. Warmuth-Metz, R.-D. Kortmann, T. Pietsch, A. Gnekow, N. Jorch, G. Janssen, F. Berthold, J. E. Wolff
Journal: Neuro-Oncology (2011)

Pediatric high-grade gliomas (HGGs) of the thalamic region account for up to 13% of pediatric HGGs and usually result in only anecdotal long-term survival. Because very little is known about these tumors, we aimed to further characterize them. In our series of 99 pediatric thalamic HGGs, there were no significant differences in survival between patients with tumors affecting the thalamus alone (including bithalamic lesions) and patients with tumors affecting the thalamus plus adjacent structures. Tumor resection (event-free survival/overall survival) and an early treatment response to radiotherapy/chemotherapy (event-free survival) had independent prognostic significance, as shown by Kaplan-Meier and multivariate Cox regression analyses. When we compared clinical characteristics and outcomes of pediatric thalamic HGG with those of pediatric (nonthalamic) supratentorial (n = 177) as well as pediatric pontine HGG (including diffuse intrinsic pontine gliomas; n = 234), we found that thalamic HGG shared more similarities with pontine than with supratentorial HGG, but overall, it appeared to represent a clinically distinct subgroup of pediatric HGG. The varying extent of tumor resection in the different tumor localizations may play some role in the observed clinical differences, as shown by multivariate Cox regression analyses, but the tumor site itself was also identified as an independent prognostic parameter. Thus, an additional location-specific effect on survival and/or tumor biology, despite different neurosurgical accessibility, has to be considered. Therefore, future investigations should try to further characterize the obviously site-specific heterogeneity of pediatric HGG on a molecular genetic basis.
Exhaled nitric oxide predicts lung function decline in difficult-to-treat asthma
Authors: I. H. van Veen, A. ten Brinke, P. J. Sterk, J. K. Sont, S. A. Gauw, K. F. Rabe, E. H. Bel
Journal: European Respiratory Journal (2008)

A subset of patients with asthma is known to have progressive loss of lung function despite treatment with corticosteroids. The aim of the present study was to identify risk factors of decline in forced expiratory volume in one second (FEV(1)) in patients with difficult-to-treat asthma. In total, 136 nonsmoking patients with difficult-to-treat asthma were recruited between 1998 and 1999. Follow-up assessment was performed 5-6 yrs later in 98 patients. The predictive effect of clinical characteristics and inflammatory markers were analysed at baseline (asthma onset and duration, atopy, airway hyperresponsiveness, blood and sputum eosinophils, and the fraction of nitric oxide in exhaled air (F(eNO))) on subsequent decline in post-bronchodilator FEV(1). Patients with high F(eNO) (> or =20 ppb) had an excess decline of 40.3 (95% confidence interval (CI) 7.3-73.2) mL.yr(-1) compared to patients with low F(eNO). F(eNO) > or =20 ppb was associated with a relative risk of 1.9 (95% CI, 1.1-2.6) of having an accelerated (> or =25 mL.yr(-1)) decline in FEV(1). In patients with baseline FEV(1) > or =80% of predicted, this relationship was even stronger: 90 versus 29% had accelerated decline in FEV(1) (F(eNO) > or =20 ppb versus F(eNO) <20 ppb respectively; relative risk 3.1 (95% CI, 1.7-3.4). Exhaled nitric oxide is a predictor of accelerated decline in lung function in patients with difficult-to-treat asthma, particularly if forced expiratory volume in one second is still normal.
Identification of a clonally restricted 90 kD heterodimer on two human cloned natural killer cell lines. Its role in cytotoxic effector function.
Authors: T Hercend, S Meuer, A Brennan, M A Edson, O Acuto, E L Reinherz, S F Schlossman, J Ritz
Journal: The Journal of Experimental Medicine (1983)

The present studies were carried out to identify surface molecules involved in the cytotoxic effector function of a human natural killer (NK) clone termed JT9. This clone represents a mature T lymphocyte (T3+T8+T11+) mediating NK-like activity. Using JT9 for immunization, one monoclonal antibody termed anti-NKTa was selected that blocked the cytotoxicity of the clone towards K562 cells. Reactivity of anti-NKTa antibody was assessed using a large panel of lymphoid and nonlymphoid cells including a variety of cloned cell lines with either cytotoxic T lymphocyte (CTL) or NK-like activity. Among all cells tested, only two individual clones, JT9 and JT10, were found to express NKTa antigen. JT10 was derived independently from the same individual as JT9 and also represents a mature T cell (T3+T8+T11+) mediating NK-like activity. Like the Ti structure on CTL clones, the molecule defined by anti-NKTa was shown to be membrane associated with T3 in co-modulation experiments. Moreover, anti-NKTa precipitated a 90 kD heterodimeric structure in sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of 125I surface-labeled JT9 cells. The blocking capacity of anti-NKTa was evaluated in cytotoxicity assays using a panel of target cells. The influence of anti-T3 was tested in parallel and it was found that both anti-NKTa and anti-T3 blocked the cytotoxicity of the cloned cells against all targets. Given the potential role of 90 kD molecules as antigen-receptor structures, the specificity of the two NKTa+ NK clones was compared and found superimposable when assessed using 15 in vitro established cell lines. However, in contrast to conventional CTL clones, the expression of cytotoxicity by JT9 and JT10 was not dependent upon recognition of class I or class II major histocompatibility complex gene products on the target cells. In addition, the cytotoxicity of these T8+ NK active clones could not be blocked by anti-T8 antibodies. Taken together, the present data suggest that the specificity of one population of human NK active lymphocytes is determined by clonotypic structures. The NKTa determinant identified here appears to belong to the same family of molecules as Ti structures, previously identified on antigen-specific T lymphocytes.
26 SEMAPHORIN 7A IS EXPRESSED IN HEPATIC STELLATE CELLS AND ENHANCES HEPATIC FIBROSIS IN A TGFβ-MEDIATED MECHANISM
Authors: S. De Minicis, C. Rychlicki, S. Saccomanno, L. Trozzi, C. Candelaresi, L. Agostinelli, F. Orlando, M. Marzioni, A. Benedetti, G. Svegliati-Baroni
Journal: Journal of Hepatology (2009)