tbuckley/cabot-search huggingface dataset:
Breast-Feeding Modulates the Influence of the Peroxisome Proliferator–Activated Receptor-γ (<i>PPARG2</i>) Pro12Ala Polymorphism on Adiposity in Adolescents
Authors: Caroline Verier, Aline Meirhaeghe, Szilvia Bokor, Christina Breidenassel, Yannis Manios, Dénes Molnár, Enrique G. Artero, Esther Nova, Stefaan De Henauw, Luis A. Moreno, Philippe Amouyel, Idoia Labayen, Noemi Bevilacqua, Dominique Turck, Laurent Béghin, Jean Dallongeville, Frédéric Gottrand
Journal: Diabetes Care (2009)

OBJECTIVE The peroxisome proliferator–activated receptor-γ2 (PPARG2) Pro12Ala polymorphism has been associated with a higher BMI and a lower risk of type 2 diabetes in adulthood. The association between adiposity and PPARG variants can be influenced by environmental factors such as early growth, dietary fat, and (as recently shown) breast-feeding. The objectives of this study were to assess 1) the influence of the PPARG2 Pro12Ala polymorphism on adiposity markers in adolescents and 2) a possible modulating effect of breast-feeding on these associations. RESEARCH DESIGN AND METHODS Data on breast-feeding duration, BMI, and genotypes for the Pro12Ala polymorphism were available for 945 adolescents (mean age 14.7 years). The breast-feeding duration was obtained from parental records. We measured weight, height, waist circumference, and six skinfold thicknesses. RESULTS No significant associations between the Pro12Ala polymorphism and any of the above-mentioned anthropometric parameters were found. There were significant interactions between the PPARG2 Pro12Ala polymorphism and breast-feeding with regard to adiposity measurements (all adjusted P &amp;lt; 0.05). Indeed, in children who had not been breast-fed, Ala12 allele carriers had higher adiposity parameters (e.g., Δ BMI +1.88 kg/m2, adjusted for age, sex, and center, P = 0.007) than Pro12Pro adolescents. In contrast, in breast-fed subjects, there was no significant difference between Ala12 allele carriers and Pro12Pro children in terms of adiposity measurements, whatever the duration of breast-feeding. CONCLUSIONS Breast-feeding appears to counter the deleterious effect of the PPARG2 Pro12Ala polymorphism on anthropometric parameters in adolescents.
762 ADDITIONAL PEG-INTERFERON IN HBeAg-POSITIVE HIV CO-INFECTED PATIENTS ON cART INCLUDING TENOFOVIR: THE ANRS HB01 EMVIPEG STUDY
Authors: P. Miailhes, M. Maynard-Muet, F. Lebosse, F. Carrat, C. Bouix, C. Lascoux-Combe, P. Sogni, S. Pol, P. Cacoub, F. Zoulim, L. Piroth
Journal: Journal of Hepatology (2013)
Factor B, the complement alternative pathway serine proteinase, is a major constitutive protein synthesized and secreted by resident and elicited mouse macrophages.
Authors: J S Sundsmo, J R Chin, R A Papin, D S Fair, Z Werb
Journal: The Journal of Experimental Medicine (1985)

Factor B, the complement alternative pathway serine proteinase, a class III gene product of the major histocompatibility complex, is a major constitutive secretion product of mouse mononuclear phagocytes. This glycoprotein was synthesized and secreted by macrophages as a doublet of Mr 90,000 and 93,000 polypeptides that were immunoprecipitable with antibodies raised to human serum factor B, and that were indistinguishable from plasma factor B by immunoreactivity, peptide mapping, and molecular weight. Macrophage factor B was cleaved and activated to factor Bb- and Ba-like fragments by factor D and cobra venom factor. Some conversion of macrophage factor B to Bb-sized fragments occurred spontaneously in the conditioned culture medium after several hours. Factor B represented approximately 0.5% of newly synthesized protein and 4-6% of the secreted protein of resident peritoneal macrophages and macrophages elicited with thioglycollate broth, pyran copolymer, NaIO4, bacillus Calmette-Guerin, or Corynebacterium parvum. We detected synthesis of factor B immediately upon explanting these macrophages in culture; synthesis continued for several days in culture. The rate of secretion of factor B, as a proportion of total protein secretion in culture, remained constant with time. By radioimmunoassay, factor B antigens accumulated in the 24-h macrophage-conditioned culture medium at 2-10 nM, and was present in cell lysates at 4-8 nmol per 10(6) cells. We detected synthesis of factor B in bone marrow-derived macrophages as early as 5 d of culture. The P388D1 macrophage line synthesized factor B, but mouse L cells did not. In contrast, apolipoprotein E, another secreted protein of macrophages, was secreted by resident and thioglycollate-elicited macrophages but not by freshly harvested pyran copolymer-activated macrophages. Its synthesis was initiated at day 9 in culture of bone marrow-derived macrophages. These data support the classification of factor B as a constitutive biosynthetic and secreted protein of immature and mature macrophages in various states of activation. Production of factor B was modulated by treatment of macrophages in vivo or in culture with bacterial lipopolysaccharide endotoxin, which increased the synthesis, secretion, and accumulation of factor B up to 11-fold.
Role of the gonads in hypertension-prone rats.
Authors: L K Dahl, K D Knudsen, E V Ohanian, M Muirhead, R Tuthill
Journal: The Journal of Experimental Medicine (1975)

In a genetically hypertension-prone (S) strain of rats it was observed previously that males generally developed hypertension more rapidly on a high salt diet than did females although final pressure ultimately were similar in both sexes. A genetic study had shown that there was no sex-linkage involved in setting blood pressure levels, so it was thought that the gonads might be involved. In the present work, castration of males had no effect on blood pressure but in the females it caused a rise in pressure that could not be distinguished from that in males, both on a high and low salt diet. Castration resulted in greater growth in females than in controls, whereas it had the opposite effect in males. It was speculated that these changes were due to influences on pituitary growth hormone with castration increasing the net output of growth hormone (or enhancing receptor sensitivity to it) in the female and the opposite in the male. From the work of others, there are some data compatible with such an interpretation. Experimentally, growth hormone will induce hypertension in rats. Therefore, it is conceivable that growth hormone is involved in the increment in hypertension observed in these castrate females. Because the effect on blood pressure was observed in castrate females on both high and low NaCl diets, it was considered unlikely that the blood pressure effect was simply due to increased NaCl intake in the food associated with greater growth. It was suggested that this rise in blood pressure with cessation of ovarian function might bear on the unsettled question of "menopausal" hypertension in women: in the genetically susceptible individual an increase in growth hormone associated with declining ovarian funtion in the menopause could provide the stimulus for the appearance of hypertension some years earlier than would otherwise have been the case.
Viral Myocarditis
Authors: Peter P. Liu, M. Anne Opavsky
Journal: Circulation Research (2000)

iral myocarditis exhibits different clinical phenotypes depending on the age of the patient.In pediatric patients, viral myocarditis can present as acute heart failure and cardiogenic shock, and in older patients, it often presents as chronic, slowly progressive heart failure and dilated cardiomyopathy.The severity of viral myocarditis is determined by a delicate balance between the viral infection and the inflammatory response that is engendered in the host.The commonest viral causes of human myocarditis include coxsackievirus B group and adenovirus.It is no accident that these two viruses emerged as the commonest etiological agent of myocarditis.Recent elegant work by Bergelson et al 1 demonstrated that both of these viruses share a common cell surface receptor-coxsackie-adenoviral receptor (CAR).CAR is a 46-kDa member of the immunoglobulin (Ig) superfamily, featuring the Ig loops maintained by disulphide bonds between appropriately positioned cysteines.The extracellular domain is the key functional component for coxsackievirus internalization. 2 CAR also serves as an attachment receptor for adenovirus.However, the natural function and regulation of CAR are still relatively unknown.The efficiency in targeting the host cell by coxsackievirus and adenovirus depends on their distinct coreceptors.Coxsackievirus B (CVB) uses the complement deflecting protein decay accelerating factor (DAF, CD55) as its coreceptor, 3 whereas adenovirus uses integrin ␣ v ␤ 3 and ␣ v ␤ 5 as its coreceptors. 4DAF as a coreceptor serves an important function by significantly increasing the binding efficiency of coxsackievirus onto the DAF-CAR receptor complex to facilitate internalization by CAR. 5
Trastuzumab in the Treatment of Breast Cancer
Authors: Gabriel N. Hortobagyi
Journal: New England Journal of Medicine (2005)

Two articles in this issue of the Journal report on the considerable therapeutic benefit of trastuzumab, a monoclonal antibody, in primary breast cancer, as measured by reductions in the rates of both recurrence and death.1,2 These reports, which complete the bench-to-bedside cycle, are elegant examples of translational research. The human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor (EGFR) family of transmembrane tyrosine kinases and is normally involved in the regulation of cell proliferation. The HER2 gene, located on the short arm of chromosome 17, was discovered and cloned in 1983 and . . .
The Experience of Symptoms of Depression in Men vs Women
Authors: Lisa A. Martin, Harold W. Neighbors, Derek M. Griffith
Journal: JAMA Psychiatry (2013)

When men are depressed they may experience symptoms that are different than what is included in the current diagnostic criteria.To explore whether sex disparities in depression rates disappear when alternative symptoms are considered in the place of, or in addition to, more conventional depression symptoms. DESIGN, SETTING, PARTICIPANTS, AND MAIN OUTCOMES AND MEASURES: Using data from the National Comorbidity Survey Replication, a nationally represented mental health survey, we evaluated sex differences in symptom endorsement in 2 new scales that included alternative depression symptoms. We analyzed sex differences in symptom endorsement using 2-sided, design-based, .05-level t tests and multivariate logistic regression to identify predictors of depression. RESULTS; Men reported higher rates of anger attacks/aggression, substance abuse, and risk taking compared with women. Analyses using the scale that included alternative, male-type symptoms of depression found that a higher proportion of men (26.3%) than women (21.9%) (P = .007) met criteria for depression. Analyses using the scale that included alternative and traditional depression symptoms found that men and women met criteria for depression in equal proportions: 30.6% of men and 33.3% of women (P = .57).When alternative and traditional symptoms are combined, sex disparities in the prevalence of depression are eliminated. Further study is needed to clarify which symptoms truly describe men's experiences of depression.
Caspase-3 Gene Deletion Prolongs Survival in Polycystic Kidney Disease
Authors: Yunxia Tao, Iram Zafar, Jun Kim, Robert W. Schrier, Charles L. Edelstein
Journal: Journal of the American Society of Nephrology (2008)

Pan-caspase inhibition reduces tubular apoptosis and proliferation and slows progression of disease in a rat model of polycystic kidney disease (PKD). It is unknown, however, which specific caspases are involved in PKD progression. Because caspase-3 is a major mediator of apoptosis, its role in
Boron-Containing Nucleosides as Potential Delivery Agents for Neutron Capture Therapy of Brain Tumors
Authors: Rolf F. Barth, Weilian Yang, Ashraf S. Al-Madhoun, Jayaseharan Johnsamuel, Youngjoo Byun, Subhash Chandra, Duane R. Smith, Werner Tjarks, Staffan Eriksson
Journal: Cancer Research (2004)

Abstract The purpose of the present study was to evaluate both in vitro and in vivo a series of boron-containing nucleosides that potentially could be used as delivery agents for neutron capture therapy. The rationale for their synthesis was based on the fact that proliferating neoplastic cells have increased requirements for nucleic acid precursors, and, therefore, they should preferentially localize in the tumor. A series of 3-carboranlyalkyl thymidine analogs has been synthesized and a subset, designated N4, N5, and N7, and the corresponding 3-dihydroxypropyl derivatives, designated N4–2OH, N5–2OH, and N7–2OH, have been selected for evaluation. Using these compounds as substrates for recombinant human thymidine kinase-1 and the mitochondrial isoenzyme thymidine kinase-2, the highest phosphorylation levels relative to thymidine were seen with N5 and the corresponding dihydroxypropyl analog N5–2OH. In contrast, N4, N4-OH, N7, and N7-OH had substantially lower phosphorylation levels. To compare compounds with high and low thymidine kinase-1 substrate activity, N5 and N7 and the corresponding dihydroxypropyl derivatives were selected for evaluation of their cellular toxicity, uptake and retention by the F98 rat glioma, human MRA melanoma, and murine L929 cell lines, all of which are thymidine kinase-1(+), and a mutant L929 cell line that is thymidine kinase-1(−). N5–2OH was the least toxic (IC50, 43–70 μm), and N7 and N7–2OH were the most toxic (IC50, 18–49 μm). The highest boron uptake was seen with N7–2OH by the MRA 27 melanoma and L929 wild-type (wt) cell lines. The highest retention was seen with L929 (wt) cells, and this ranged from 29% for N5–2OH to 46% for N7. Based on the in vitro toxicity and uptake data, N5–2OH was selected for in vivo biodistribution studies either in rats bearing intracerebral implants of the F98 glioma or in mice bearing either s.c. or intracerebral implants of L929 (wt) tumors. At 2.5 hours after convection-enhanced delivery, the boron values for the F98 glioma and normal brain were 16.2 ± 2.3 and 2.2 μg/g, respectively, and the tumor to brain ratio was 8.5. Boron values at 4 hours after convection-enhanced delivery of N5–2OH to mice bearing intracerebral implants of L929 (wt) or L929 thymidine kinase-1(−) tumors were 39.8 ± 10.8 and 12.4 ± 1.6 μg/g, respectively, and the corresponding normal brain values were 4.4 and 1.6 μg/g, thereby indicating that there was selective retention by the thymidine kinase-1(+) tumors. Based on these favorable in vitro and in vivo data, neutron capture therapy studies will be initiated using N5–2OH in combination with two non-cell cycle dependent boron delivery agents, boronophenylalanine and sodium borocaptate.
Quantifying Transient Hypoxia in Human Tumor Xenografts by Flow Cytometry
Authors: Kevin L. Bennewith, Ralph E. Durand
Journal: Cancer Research (2004)

Abstract Transient hypoxia is a poorly understood and potentially important factor that may limit tumor response to various forms of therapy. We assessed transient hypoxia on a global scale in two different human tumor xenografts by sequentially administering two hypoxia markers followed by quantification of hypoxic cells using flow cytometry. High levels of the first hypoxia marker (pimonidazole) were maintained in the circulation over an 8-hour period by multiple hourly injections, providing a “time-integrated” hypoxia measure showing an asymptotic increase in the total number of hypoxic cells. Subsequent administration of a second hypoxia marker (CCI-103F) showed that substantial numbers of the previously pimonidazole-labeled cells were no longer hypoxic during the circulation lifetime of the second marker. The overall fraction of tumor cells that demonstrated changes in hypoxic status with time increased with different kinetics and by different magnitudes in the two xenograft systems. Specifically, up to 20% of the cells in SiHa (human cervical squamous cell carcinoma) tumors and up to 8% of the cells in WiDr (human colon adenocarcinoma) tumors were intermittently hypoxic over an 8-hour period. Also, the tumor cells that demonstrated transient hypoxia were typically not adjacent to functional tumor blood vessels. Similar approaches could be used in the clinic to provide information on the duration of intermittent hypoxia episodes and the fraction of transiently hypoxic tumor cells, which would, in turn, have important implications for the strategic improvement of cancer therapy.
Glass Microelectrode Studies on Intramural Papillary Muscle Cells
Authors: LLOYD E. SOLBERG, DONALD H. SINGER, ROBERT E. TEN EICK, EDWIN G. DUFFIN
Journal: Circulation Research (1974)

Although the electrophysiological properties of intramural ventricular myocardial cells are important to an understanding of cardiac excitation and conduction, they have not been well defined. The paucity of information stems from limitations on the depth of penetration by glass microelectrodes and from difficulties in perfusing the deep layers. Therefore, a tissue slicing technique that satisfactorily exposes all the layers of a papillary muscle specimen from the endocardium to the epicardium was developed for electrophysiological examination. Glass microelectrodes were then used to explore these slice preparations to define the electrophysiological characteristics of intramural cells in the normal dog. Transmem-brane potentials recorded from subendocardial and deep myocardial cells in the papillary muscle slices were comparable to those recorded from standard preparations. Similarities included action potential duration and configuration, relationships among resting potential, action potential configuration, and extracellular potassium concentration, and dependency of action potential duration on cycle length. However, the average magnitudes of measured electrophysiological characteristics were consistently greater in the subsurface cells tested in papillary muscle slices than they were in the surface cells tested in the standard preparations, i.e., resting potential was 2-4 my more negative, action potential amplitude was 7-9 my larger, and maximum rate of voltage change (maximum dV/dt) was 40-140 v/sec larger. Deep myocardial tissues also exhibited enhanced responsiveness (the curve relating activation potential to maximum dV/dt of the response shifted up and to the left), cell populations with large maximum dV/dt, and estimated conduction velocities in excess of three times those in the surface cell layers. These findings provide a reasonable explanation for (1) discrepancies between previously reported values for ventricular conduction velocity, (2) rapid impulse spread to the papillary muscle tip, and (3) bidirectional activation of the papillary muscle and large trabeculae. They also suggest the possibility of functional pathways that facilitate rapid activation of the deep myocardial lavers.
The Hurrider I Go the Behinder I Get: The Deteriorating International Ranking of U.S. Health Status
Authors: Stephen Bezruchka
Journal: Annual Review of Public Health (2012)

The health of societies can be measured by a range of mortality indicators, and comparisons of national parameters with those of other societies can be symbolic of health status and progress. Over the past century, health outcomes have been steadily improving almost everywhere in the world, but the rates of improvements have varied. In the 1950s, the United States, having among the lowest mortality and other indicators of good health, ranked well among nations. Since then, the United States has not seen the scale of improvements in health outcomes enjoyed by most other developed countries, despite spending increasing amounts of its economy on health care services. Trends in personal health-related behaviors are only part of the explanation. Structural factors related to inequality and conditions of early life are important reasons for the relative stagnation in health. Reversing this relative decline would require a major national coordinated long-term effort to expose the problem and create the political will to address it.
A Systematic Review of Single-Session Psychological Interventions (‘Debriefing’) following Trauma
Authors: Suzanna Rose, Jonathan Bisson, Simon Wessely
Journal: Psychotherapy and Psychosomatics (2003)

Single-session psychological interventions such as psychological debriefing have become widely used following traumatic events. The evidence for their effectiveness has been widely debated. This review aimed to consider the evidence for the effectiveness of one-off early interventions within 1 month of a traumatic event.A systematic review using the standard Cochrane Collaboration methodology. Literature searches of various databases were performed to identify randomised controlled trials. The methodological quality of the studies identified was determined using standard measures, and the results were pooled to consider the overall evidence for effectiveness.Eleven randomised controlled trials were found, all of individual or couple interventions. Three studies associated the intervention with a positive outcome, 6 demonstrated no difference in outcome between intervention and non-intervention groups and 2 showed some negative outcomes in the intervention group (these studies had the longest follow-up periods). The methodological quality of the studies varied widely, but was generally poor. This review suggests that early optimism for brief early psychological interventions including debriefing was misplaced and that it should not be advocated for routine use. There remains an urgent need for randomised controlled trials of group debriefing and other early interventions.
Human CLC-KB Gene Promoter Drives the EGFP Expression in the Specific Distal Nephron Segments and Inner Ear
Authors: Katsuki Kobayashi, Shinichi Uchida, Hiro-oki Okamura, Fumiaki Marumo, Sei Sasaki
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Human CLC-KB has been identified as a kidney-specific member of the CLC chloride channel family, and mutations of the human CLC-KB gene are known to cause Bartter syndrome type III. A precise understanding of the localization of this channel in the human kidney is imperative to our understanding of the pathophysiology, but this has remained unclear due to the high homology between human CLC-KB and CLC-KA, another kidney-specific member of the same family. The high intraspecies homology also rules out an exact correlation of the human isoforms (CLC-KA and CLC-KB) to the mouse and rat isoforms (CLC-K1 and CLC-K2, respectively). This study created transgenic mice harboring the enhanced green fluorescence protein (EGFP) gene driven by an 11-kbp human CLC-KB gene promoter. Three transgenic lines were generated, and all of them showed EGFP fluorescence in the kidney, with an identical pattern of localization to the thick ascending limb of Henle's loop, distal tubules, connecting tubules, and intercalated cells of the collecting duct. This localization is exactly the same as that of mouse CLC-K2 identified in a previous report (Kobayashi et al. J Am Soc Neph 12: 1327–1334, 2001). EGFP fluorescence was also detected in the inner ear, more specifically in marginal cells of the stria vascularis and dark cells of the vestibular labyrinth, suggesting that human CLC-KB could play an important role in the fluid transport mechanism of the inner ear. The results (1) confirmed that CLC-KB is the true human homologue of rat and mouse CLC-K2 and (2) established that the 11-kbp human CLC-KB gene promoter is sufficient to elicit the precise expression in specific cell types of the kidney and inner ear.