tbuckley/cabot-search huggingface dataset:
<i>In Utero</i> Exposure to Di( <i>n</i> -butyl) Phthalate and Testicular Dysgenesis: Comparison of Fetal and Adult End Points and Their Dose Sensitivity
Authors: I. Kim Mahood, Hayley M. Scott, Richard Brown, Nina Hallmark, Marion Walker, Richard M. Sharpe
Journal: Environmental Health Perspectives (2007)

BackgroundFetal exposure of male rats to di(n-butyl) phthalate (DBP) induces reproductive disorders similar to those in human testicular dysgenesis syndrome (TDS), including infertility, cryptorchidism, focal “dysgenetic areas,” and Sertoli cell–only tubules in the adult testis. Humans are widely exposed to DBP, but at much lower levels than those causing adverse effects in rats.ObjectivesThe objective of this study was to evaluate end points affected by DBP action in rats in fetal and adult life that are relevant to human TDS, and to compare their dose sensitivity.MethodsPregnant rats were gavaged daily with corn oil (control) or with 4, 20, 100, or 500 mg/kg DBP. We examined adult end points of TDS (infertility, cryptorchidism) and indicators within the fetal testis of dysgenesis [abnormal Leydig cell (LC) aggregation, multinucleated gonocytes (MNGs)], as well as conditions that may result from these indicators in adulthood (occurrence of focal dysgenetic areas). Fetal testis weight and testicular testosterone levels were also evaluated.ResultsThe fetal end points analyzed (testicular testosterone levels, abnormal LC aggregation, occurrence of MNGs) were most sensitive to disruption by DBP, as all were significantly affected at a dose of 100 mg/kg/day DBP, with a trend toward effects occurring at 20 mg/kg/day DBP; adult end points were affected consistently only by 500 mg/kg/day DBP.ConclusionsThe fetal end points we evaluated can be objectively quantified and may prove helpful in evaluating the health risk of exposure to DBP and other phthalates, as well as identifying DBP-sensitive fetal events that have adult consequences/end points that are identifiable in human TDS.
A European multicentre photopatch test study
Journal: British Journal of Dermatology (2012)

The two most common agent groups currently responsible for photoallergic contact dermatitis (PACD) are organic ultraviolet (UV) absorbers in sunscreens and topical nonsteroidal anti-inflammatory drugs (NSAIDs). However, availability of information on the photoallergenic potential of these agents is scarce.To obtain current information on the frequency of PACD to 19 organic UV absorbers and five topical NSAIDs, including newer agents, in common usage in Europe.A prospective, multicentre photopatch test study was conducted with 1031 patients attending for investigation of suspected PACD in 30 centres across 12 European countries.A total of 346 PACD reactions in 200 (19·4%) subjects occurred. PACD was most commonly caused by the topical NSAIDs, ketoprofen (128 subjects) and etofenamate (59 subjects). Of the organic UV absorbers, octocrylene, benzophenone-3 and butyl methoxydibenzoylmethane most frequently elicited PACD. The 'newer' organic sunscreen absorbers rarely led to PACD. There appeared to be an association between the agents ketoprofen, octocrylene and benzophenone-3, with several subjects developing PACD to two or all three agents concomitantly. Allergic contact dermatitis (ACD) was less commonly observed than PACD, comprising 55 reactions in 47 (5%) subjects. Irritant reactions and photoaugmentation and photoinhibition of ACD occurred infrequently.The European multicentre photopatch test study has provided current information on the relative frequency of PACD to common photoallergens. Such data will be of value when deciding on which agents to include in a future European 'baseline' photopatch test series.
Mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80. Identification of resident macrophages in renal medullary and cortical interstitium and the juxtaglomerular complex
Authors: DA Hume, S Gordon
Journal: The Journal of Experimental Medicine (1983)

Macrophages have been identified in mouse kidney by immunohistochemical localization of the macrophage-specific antigen F4/80. They constitute the majority of the renal medullary interstitial cell population and are also found in contact with cortical distal and proximal tubules and Bowman's capsule. They are a physical component of the juxtaglomerular complex.
Evaluation of the validity of the different arms of the ASAS set of criteria for axial spondyloarthritis and description of the different imaging abnormalities suggestive of spondyloarthritis: data from the DESIR cohort
Authors: Anna Moltó, Simon Paternotte, Désirée van der Heijde, Pascal Claudepierre, Martin Rudwaleit, Maxime Dougados
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The Assessment of Spondyloarthritis International Society (ASAS) criteria for axial spondyloarthritis (SpA) allows classification of patients with ('imaging' arm) and without ('clinical' arm) imaging abnormalities of the sacroiliac joints. <h3>Objective</h3> To compare the phenotype of early axial SpA with regard to the two arms of the ASAS axial SpA criteria. <h3>Methods</h3> Demographics, clinical and biological features of SpA, disease activity, severity parameters, and imaging abnormalities at the sacroiliac and spine levels were compared, in the two arms of the ASAS axial SpA criteria, in the patients of the French cohort of early SpA. <h3>Results</h3> Of the 615 patients analysed, 435 (70.7%) met the ASAS criteria (262 (60.2%) and 173 (39.8%) in the imaging and clinical arms, respectively). There were no major differences in the characteristics of the two groups except that those in the imaging arm were more likely to be younger, male and have higher concentrations of C-reactive protein. Imaging abnormalities other than those meeting the ASAS criteria for the imaging arm (ie, x-ray-determined structural damage or MRI-revealed inflammatory changes in the sacroiliac joint (SIJ)) were observed (MRI–SIJ structural damage (55.0% vs 3.5%), MRI–spine inflammatory changes (35.1% vs 12.9%), MRI–spine structural damage (10.3% vs 5.3%) and x-ray–syndesmophytes (11.8% vs 5.3%)) in the imaging versus clinical arm, respectively. <h3>Conclusions</h3> Our study confirms the external validity of the clinical arm of the ASAS criteria. It is notable that many patients in the clinical arm showed other imaging changes in SIJs and spine.
Pulmonary rehabilitation and readmissions in COPD: Authors' reply
Authors: William D-C Man, John Moxham
Journal: BMJ (2005)

Learning from low income countries Experience in low income countries should count towards specialist registrar trainingEditor-Richards and Tumwine ask for discussion on the subject of poor countries making the best teachers. 1When will the postgraduate tutors and royal colleges recognise that medical experience in developing countries should be counted towards specialist registrar training?I recently spoke to a specialist registrar whose 12 months in the main teaching hospital in Malawi counted for nothing towards his training.As a specialist registrar training in chest medicine, he will have seen more tuberculosis than most chest physicians working in provincial England will see in a lifetime.This is particularly frustrating as the numbers of cases of tuberculosis are rising progressively in the United Kingdom, and training in the diagnosis and management of this disease needs to be improved as much as possible.
Response assessment criteria for brain metastases: proposal from the RANO group
Authors: Nancy U Lin, Eudocia Q Lee, Hidefumi Aoyama, Igor J Barani, Daniel P Barboriak, Brigitta G Baumert, Martin Bendszus, Paul D Brown, D Ross Camidge, Susan M Chang, Janet Dancey, Elisabeth G E de Vries, Laurie E Gaspar, Gordon J Harris, F Stephen Hodi, Steven N Kalkanis, Mark E Linskey, David R Macdonald, Kim Margolin, Minesh P Mehta, David Schiff, Riccardo Soffietti, John H Suh, Martin J van den Bent, Michael A Vogelbaum, Patrick Y Wen
Journal: The Lancet Oncology (2015)
Setting Research Priorities to Reduce Mortality and Morbidity of Childhood Diarrhoeal Disease in the Next 15 Years
Authors: Kerri Wazny, Alvin Zipursky, Robert Black, Valerie Curtis, Christopher Duggan, Richard Guerrant, Myron Levine, William A. Petri, Mathuram Santosham, Rebecca Scharf, Philip M. Sherman, Evan Simpson, Mark Young, Zulfiqar A. Bhutta
Journal: PLoS Medicine (2013)

Zulfi Bhutta and colleagues lay out research priorities for global child diarrheal disease over the next 15 years, which they developed using the Child Health and Nutrition Research Initiative (CHNRI) method. Please see later in the article for the Editors' Summary
PEGylated Exendin-4, a Modified GLP-1 Analog Exhibits More Potent Cardioprotection than Its Unmodified Parent Molecule on a Dose to Dose Basis in a Murine Model of Myocardial Infarction
Authors: Zhongchan Sun, Guang Tong, Tae Hyung Kim, Nan Ma, Gang Niu, Feng Cao, Xiaoyuan Chen
Journal: Theranostics (2014)

A Site-specifically PEGylated exendin-4 (denoted as PEG-Ex4) is an exendin-4 (denoted as Ex4) analog we developed by site-specific PEGylation of exendin-4 with a high molecular weight trimeric poly(ethylene glycol) (tPEG).It has been shown to possess prolonged half-life in vivo with similar receptor binding affinity compared to unmodified exendin-4 by our previous work.This study is sought to test whether PEG-Ex4 is suitable for treating myocardial infarction (MI).In the MI model, PEG-Ex4 was administered every 3 days while equivalent amount of Ex4 was administered every 3 days or twice daily.Animal survival rate, heart function, remodeling and neoangiogenesis were evaluated and compared.Tube formation was examined in endothelial cells.In addition, Western blotting and histology were performed to determine the markers of cardiac hypertrophy and angiogenesis and to explore the possible molecular mechanism involved.PEG-Ex4 and Ex4 showed comparable binding affinity to GLP-1 receptor.In MI mice, PEG-Ex4 given at 3 days interval achieved similar extent of protection as Ex4 given twice daily, while Ex4 given at 3 days interval failed to produce protection.PEG-Ex4 elevated endothelial tube formation in vitro and capillary density in the border area of MI.PEG-Ex4 increased Akt activity and VEGF production in a GLP-1R dependent manner in endothelial cells and antagonism of GLP-1R, Akt or VEGF abolished the protection of PEG-Ex4 in the MI model.PEG-Ex4 is a potent long-acting GLP-1 receptor agonist for the treatment of chronic heart disease.Its protection might be attributed to enhanced angiogenesis mediated by the activation of Akt and VEGF.
Renal Myogenic Response
Authors: Rodger Loutzenhiser, Anil Bidani, Lisa Chilton
Journal: Circulation Research (2002)

The kinetic attributes of the afferent arteriole myogenic response were investigated using the in vitro perfused hydronephrotic rat kidney. Equations describing the time course for pressure-dependent vasoconstriction and vasodilation, and steady-state changes in diameter were combined to develop a mathematical model of autoregulation. Transfer functions were constructed by passing sinusoidal pressure waves through the model. These findings were compared with results derived using data from instrumented conscious rats. In each case, a reduction in gain and increase in phase were observed at frequencies of 0.2 to 0.3 Hz. We then examined the impact of oscillating pressure signals. The model predicted that pressure signals oscillating at frequencies above the myogenic operating range would elicit a sustained vasoconstriction the magnitude of which was dependent on peak pressure. These predictions were directly confirmed in the hydronephrotic kidney. Pressure oscillations presented at frequencies of 1 to 6 Hz elicited sustained afferent vasoconstrictions and the magnitude of the response depended exclusively on the peak pressure. Elevated systolic pressure elicited vasoconstriction even if mean pressure was reduced. These findings challenge the view that the renal myogenic response exists to maintain glomerular capillary pressure constant, but rather imply a primary role in protecting against elevated systolic pressures. Thus, the kinetic features of the afferent arteriole allow this vessel to adjust tone in response to changes in systolic pressures presented at the pulse rate. We suggest that the primary function of this mechanism is to protect the glomerulus from the blood pressure power that is normally present at the pulse frequency.
Serum periostin levels correlate with airway hyper-responsiveness to methacholine and mannitol in children with asthma
Authors: J.-S. Song, J.-S. You, S.-I. Jeong, S. Yang, I.-T. Hwang, Y.-G. Im, H.-S. Baek, H.-Y. Kim, D.-I. Suh, H.-B. Lee, K. Izuhara
Journal: Allergy (2015)

Periostin is a matricellular protein, and its synthesis in airway epithelial cells and lung fibroblasts is induced by interleukin (IL)-4 and IL-13. The significance of periostin as a biomarker of TH 2-induced airway inflammation, and (importantly) as a measure of the response to TH 2-targeted therapy, has recently been emphasized. We explored the relationship between periostin and airway hyperresponsiveness (AHR) in asthmatic children.The study included 83 children aged 6-15 years in an asthmatic group (n = 54) and healthy controls (n = 29). We measured the periostin levels in serum and performed methacholine and mannitol provocation challenges. The responses to mannitol were expressed as the provocative dose causing a 15% fall in the FEV1 (the PD15 dose).Of the 54 subjects with asthma, all had positive methacholine bronchial provocation test (BPT) results and 38 had positive mannitol BPT results. Children with asthma had significantly higher periostin levels than controls [76.0 (65.0-91.8) vs 71.0 (57.5-80.0) ng/mL; P = 0.017]. Periostin levels were significantly correlated with both the methacholine PC20 and mannitol PD15 values.Serum levels of periostin, a new biomarker induced by IL-13, were higher in asthmatic children, and were associated with AHR to methacholine and mannitol.
Serum High-Density Lipoprotein Cholesterol, Metabolic Profile, and Breast Cancer Risk
Authors: A.-S. Furberg, M. B. Veierod, T. Wilsgaard, L. Bernstein, I. Thune
Journal: JNCI Journal of the National Cancer Institute (2004)

The prevalence of metabolic syndrome (obesity, glucose intolerance, low serum high-density lipoprotein cholesterol [HDL-C], high serum triglycerides, hypertension) is high and increasing in parallel with an increasing breast cancer incidence worldwide. HDL-C represents an important aspect of the syndrome, yet its role in breast cancer is still undefined.In two population-based screening surveys during 1977-1983 and 1985-1987, serum HDL-C was assayed enzymatically among 38,823 Norwegian women aged 17-54 years at entry. Height, weight, blood pressure, serum lipids, fat and energy intake, physical activity, parity, oral contraceptive use, hormone therapy use, alcohol intake, and tobacco use were also assessed. We used Cox proportional hazards modeling to estimate the relative risk (RR) of breast cancer associated with serum HDL-C levels and to adjust for potential confounding variables. We performed stratified analyses to evaluate effect modification by body mass index (BMI) and menopausal status. All statistical tests were two-sided.During a median follow-up of 17.2 years, we identified 708 cases of invasive breast cancer. In multivariable analysis, the risk of postmenopausal breast cancer was inversely related to quartile of HDL-C (P(trend) =.02). Among women with HDL-C above 1.64 mmol/L (highest quartile) versus below 1.20 mmol/L (lowest quartile), the relative risk was 0.75 (95% confidence interval [CI] = 0.58 to 0.97). The HDL-C association was confined to women in the heavier subgroup (BMI > or =25 kg/m2), for whom the relative risk of postmenopausal breast cancer in those with HDL-C above 1.64 mmol/L versus below 1.20 mmol/L was 0.43 (95% CI = 0.28 to 0.67; P(trend)<.001; P(interaction) =.001).Low HDL-C, as part of the metabolic syndrome, is associated with increased postmenopausal breast cancer risk.
Lack of cellular and humoral immunological responses to oats in adults with coeliac disease
Authors: E K Janatuinen
Journal: Gut (2000)

Recent research suggests that oats do not harm intestinal villi in adults with coeliac disease. As the immunological effects of oats have not been examined in detail, it was decided to compare the immunological responses of a gluten free diet including oats with those of a conventional gluten free diet.A randomised controlled intervention study over 6-12 months.Forty adults with newly diagnosed coeliac disease and 52 with coeliac disease in remission were examined.The effects of a gluten free diet including oats and a conventional gluten free diet were compared.Serum levels of gliadin and reticulin antibodies as well as numbers of intraepithelial lymphocytes (IELs) in intestinal mucosa were examined before and after the intervention.The rate of disappearance of gliadin and reticulin antibodies did not differ between the diet groups in patients with newly diagnosed coeliac disease. Oats also had no effect on gliadin or reticulin antibody levels in the patients with remission. The number of IELs decreased similarly regardless of the diet of newly diagnosed patients, and no increase in the number of IELs was found in the patients in remission with or without oats.These results strengthen the view that adult patients with coeliac disease can consume moderate amounts of oats without adverse immunological effects.
Membrane permeability as a cause of transport defects in experimental Fanconi syndrome. A new hypothesis.
Authors: M Bergeron, L Dubord, C Hausser, C Schwab
Journal: Journal of Clinical Investigation (1976)

The injection of sodium maleate (200-400 mg/kg) into rats produces aminoaciduria along with glycosuria and phosphaturia, resembling the Fanconi syndrome. This experimental model was studied by means of microinjections into proximal convoluted tubules of the kidney, stop-flow diuresis, and microperfusion of single nephrons. Our results show that, in maleate-treated rats, competition between amino acids or related structures (L-proline, L-OH-proline, and glycine) possesses the same characteristics, and net influx of amino acids appear normal at the proximal nephron. Data obtained by classical stop-flow techniques and single nephron microperfusions also indicate a normal entry of labeled amino acids (L-lysine, glycine, L-valine, L-proline, L-cystine), and 3-0-methyl-D-[3H]glucose and [32P]phosphate from the luminal side of the proximal tubule cell. However, the efflux of molecules from the cell appears enhanced throughout the proximal and distal tubule; molecules that exit at this site are excreted directly into the urine. Our results suggest that the phosphaturia, aminoaciduria, and glycosuria of the experimental Fanconi syndrome can be explained by a modification of the cell membrane permeability (increased efflux) at distal sites of the nephron rather than by a modification of the membrane transport (decreased influx) at the proximal sites, as is currently accepted. Our data also stress the importance of efflux phenomena in membrane transport.
Heart-type fatty acid-binding protein for risk assessment of chronic thromboembolic pulmonary hypertension
Authors: M. Lankeit, C. Dellas, A. Panzenböck, N. Skoro-Sajer, D. Bonderman, M. Olschewski, K. Schäfer, M. Puls, S. Konstantinides, I. M. Lang
Journal: European Respiratory Journal (2008)

Heart-type fatty acid-binding protein (H-FABP) is a reliable marker of myocardial injury and was recently identified as a predictor of outcome in acute pulmonary embolism. The aim of the present study was to investigate the prognostic value of H-FABP in chronic thromboembolic pulmonary hypertension (CTEPH). In total, 93 consecutive patients with CTEPH were studied. During long-term follow-up (median duration 1,260 days, interquartile range (IQR) 708–2,460 days), 46 (49%) patients had an adverse outcome, defined as CTEPH-related death, lung transplantation or persistent pulmonary hypertension after pulmonary endarterectomy (PEA). Baseline H-FABP levels in plasma ranged from 0.69–24.3 ng·mL −1 (median (IQR) 3.41 (2.28–4.86) ng·mL −1 ). Cox regression analysis revealed a hazard ratio of 1.10 (95% confidence interval 1.04–1.18) for each increase of H-FABP by 1 ng·mL −1 , and continuous elevations of H-FABP emerged as an independent predictor of adverse outcome by multivariable analysis. PEA was performed in 52 patients and favourably affected the long-term outcome. Kaplan–Meier analysis revealed that patients with baseline H-FABP concentrations &gt;2.7 ng·mL −1 , the median value of the biomarker in the surgically treated population, had a lower probability of event-free survival after PEA. Heart-type fatty acid-binding protein is a promising novel biomarker for risk stratification of patients with chronic thromboembolic pulmonary hypertension.
OVERLAP STIMULATION OF PRIMARY AND SECONDARY B CELLS BY CROSS-REACTING DETERMINANTS
Authors: N. R. Klinman, J. L Press, G. P. Segal
Journal: The Journal of Experimental Medicine (1973)

Experiments were carried out to test the validity of the hypothesis that postulated differences in the nature of the antigen receptors of primary and secondary B cells should be reflected in a greater specificity in primary B-cell stimulation (2). Enumeration of clonal precursors stimulated by either DNP-Hy, TNP-Hy, or a mixture of both antigens confirmed this hypothesis. Since the sum of primary B cells stimulated by DNP-Hy and TNP-Hy is approximately equal to the number stimulated by a mixture of both, overlap stimulation of primary B cells by these antigens could be considered negligible. In contrast, the stimulation of B cells from mice previously immunized with DNP-Hy showed extensive overlap of stimulation by DNP-Hy and TNP-Hy. Thus secondary B cells appear less fastidious in their affinity requirements for stimulation than primary B cells.
Evolution is important but it is not simple: Defining cultural traits and incorporating complex evolutionary theory
Authors: Agustín Fuentes
Journal: Behavioral and Brain Sciences (2006)

Examining homology in biological and cultural evolution is of great importance in investigations of humanity. The proposal presented in the target article retains substantial methodological weaknesses in the identification and use of “cultural traits.” However, with refined toolkits and the incorporation of recent advances in evolutionary theory, this overall endeavor can result in substantial payoffs for biological and social scientists.