tbuckley/cabot-search huggingface dataset:
Efficacy of allopurinol and benzbromarone for the control of hyperuricaemia. A pathogenic approach to the treatment of primary chronic gout
Authors: F Perez-Ruiz, A Alonso-Ruiz, M Calabozo, A Herrero-Beites, G Garcia-Erauskin, E Ruiz-Lucea
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVES</h3> To study the efficacy of allopurinol and benzbromarone to reduce serum urate concentrations in patients with primary chronic gout. <h3>METHODS</h3> Prospective, parallel, open study of 86 consecutive male patients with primary chronic gout. Forty nine patients (26 normal excretors and 23 under excretors) were given allopurinol 300 mg/day and 37 under excretors benzbromarone 100 mg/day. After achieving steady plasma urate concentrations with such doses, treatment was then adjusted to obtain optimal plasmatic urate concentrations (under 6 mg/dl). <h3>RESULTS</h3> Patients receiving allopurinol 300 mg/day showed a mean reduction of plasmatic urate of 2.75 mg/dl (from 8.60 to 5.85 mg/dl) and 3.34 mg/dl (from 9.10 to 5.76 mg/dl) in normal excretors and under excretors respectively. Patients receiving benzbromarone 100 mg/day achieved a reduction of plasmatic urate of 5.04 mg/dl (from 8.58 to 3.54 mg/dl). Fifty three per cent of patients receiving allopurinol and 100% receiving benzbromarone achieved optimal plasma urate concentrations at such doses. The patients with poor results with allopurinol 300 mg/day achieved a proper plasma urate concentration with allopurinol 450 to 600 mg/day, the mean final dose being 372 mg/day. Renal fuction improved and no case of renal lithiasis was observed among benzbromarone treated patients, whose mean final dose was 76 mg/day. <h3>CONCLUSION</h3> Benzbromarone is very effective to control plasma urate concentrations at doses ranging from 50 to 100 mg/day. Uricosuric treatment is a suitable approach to the treatment of patients with gout who show underexcretion of urate.
Leptin and reproduction
Authors: R R González, C Simón, P Caballero-Campo, R Norman, D Chardonnens, L Devoto, P Bischof
Journal: Human Reproduction Update (2000)

Leptin, the product of the ob gene, is a small peptide molecule synthesized by white adipocytes with an important role in the regulation of body fat and food intake. Leptin and leptin receptor mRNA were first detected in the brain and hypothalamus but now their ubiquitous presence has been demonstrated. Leptin receptor signal transduction involves the activation of signal transducer and activator of transcription (STAT)-3, a member of the transcription family of proteins. Leptin is regulated by hormones and cytokines, interleukin-1, tumour necrosis factor-alpha and transforming growth factor-beta, linking this molecule with the inflammatory response. In addition, emerging evidence has demonstrated that this molecule is related to reproductive function. This small protein is present in the ovary and decidua, in mature oocytes and during embryonic development and trophoblast invasion. Animal models have demonstrated that leptin-deficient ob/ob mice are sterile; however, fertility can be restored by exogenous leptin. In addition, embryos implanted in STAT-3-deficient mice degenerate rapidly and are the target disruption of STAT-3-provoked embryonic lethality. Leptin acts as a novel placental hormone participating in the control of fetal growth and development. Leptin could be a modulator for invasive features of cytotrophoblast cells. We postulate that leptin may have an autocrine/paracrine role in human implantation and placentation.
Clinical and subclinical intestinal inflammation assessed by the mucosal patch technique: studies of mucosal neutrophil and eosinophil activation in inflammatory bowel diseases and irritable bowel syndrome
Authors: G Kristjansson
Journal: Gut (2004)

<b>Background and aims:</b> There is a clear need for a rapid, simple, safe, and sensitive method of determining the type and intensity of inflammation in the gut mucosa in clinical practice. In this study, we have evaluated the potential of a new method, the mucosal patch technique, in patients with and without apparent gut inflammation, as assessed by conventional diagnostic procedures. <b>Subjects and methods:</b> The technique tested is based on the idea that inflammatory mediators released from the rectal mucosa can be absorbed by and then extracted from cellulose patches brought into contact with the mucosa by use of an instrument with an inflatable balloon. Measurements were performed in healthy controls (n = 16) and in patients with active (n = 19) and inactive ulcerative colitis (UC, n = 8), collagen colitis (CC, n = 12), coeliac disease (n = 13), and irritable bowel syndrome (IBS, n = 13). <b>Results:</b> Inflammatory mediators from neutrophils (myeloperoxidase (MPO)) and eosinophils (eosinophil cationic protein (ECP)) were increased on average 300- and 10-fold, respectively, in patients with active UC compared with healthy controls and were correlated with the endoscopic score. Patients with inactive UC, CC, coeliac disease, and IBS exhibited no endoscopic signs of inflammation. These patient groups had significantly lower levels of MPO and ECP than the active UC group but showed on average a four- to sevenfold increase in MPO compared with healthy controls. <b>Conclusion:</b> The mucosal patch technique was well tolerated by patients and easily applied by the investigator. Pronounced neutrophil and eosinophil involvement in UC was demonstrated. With the high sensitivity of the technique, low degree mucosal neutrophil activation could also be quantified in patients with CC and UC in clinical remission. The finding of increased neutrophil involvement in patients with IBS contributes to the pathophysiological ideas of this disease.
Preventive Counseling Among Women With Histories of Gestational Diabetes Mellitus
Authors: Catherine Kim, Laura N. McEwen, Eve A. Kerr, John D. Piette, Mark C. Chames, Assiamira Ferrara, William H. Herman
Journal: Diabetes Care (2007)

The purpose of this study was to examine the association between recall of recommendations for diabetes prevention and both health behaviors and screening among women with histories of gestational diabetes mellitus (GDM).We surveyed 228 women with histories of GDM within the past 5 years who were enrolled in a university-affiliated managed care plan. In a cross-sectional analysis, we assessed the association between recall of health care provider advice and both postpartum lifestyle behaviors and reported performance of postpartum diabetes screening. Multivariate models were constructed that adjusted for correlates of counseling including postpartum diabetes, dyslipidemia, insulin use during pregnancy, and provider type.Participants were predominantly non-Hispanic white, college educated and affluent, and overweight or obese. The majority reported that they received counseling on lifestyle modification and postpartum diabetes screening. Postpartum physical activity levels, fruit and vegetable intake, and screening were suboptimal. No significant association existed between recall of advice and physical activity or between recall of advice and diet. Recall of advice along with distribution of laboratory slips for glucose testing was associated with performance of postpartum diabetes screening using self-report (adjusted odds ratio 2.07 [95% CI 1.51-2.84]) or claims data (1.64 [1.16-2.32]).Women with histories of GDM who recalled advice regarding postpartum glucose testing and received laboratory slips were significantly more likely to report having had postpartum diabetes screening. Although women's recall of services may not reflect the actual services received, simple counseling may not be sufficient to optimize postpartum behaviors to reduce future risk of diabetes.
Contrasting gender differences on two measures of exercise dependence: Table 1
Authors: M Weik, B D Hale
Journal: British Journal of Sports Medicine (2008)

Recent studies using multidimensional measures have shown that men (Exercise Dependence Scale; EDS-R) are more exercise-dependent than women, whereas others have found that women (Exercise Dependence Questionnaire; EDQ) are more exercise-dependent than men. This study investigated whether there may be sex differences in exercise dependence or whether the questionnaires may be measuring different dimensions of exercise dependence.Regular exercisers voluntarily completed the EDS-R, EDQ and Drive for Thinness (DFT) subscale before or after a workout.A local health club in the eastern USA.Male (n = 102) and female (n = 102) exercisers completed the three questionnaires, but 11 participants (1 man, 10 women) were excluded from further analysis because scores indicated possible secondary exercise dependence (eating disorder).Eight subscales of the EDQ, seven subscales of the EDS, the DFT subscale, and several demographic variables served as dependent measures.A multivariate analysis of variance (MANOVA) on the EDS-R showed that men were significantly higher than women on the Withdrawal, Continuance, Tolerance, Lack of Control, Time, and Intention Effect subscales. Another MANOVA on the EDQ indicated that women scored significantly higher than did men on the Interference, Positive Rewards, Withdrawal, and Social Reasons subscales. Statistical analysis using t tests revealed that men had significantly higher total EDS-R scores than women, but women had significantly higher EDQ and DFT scores.These results suggest that both questionnaires measure different aspects of exercise dependence that favour either gender. It remains for further research to determine whether these instruments are equally viable for measurement of ED in both men and women.
The tumor suppressor semaphorin 3B triggers a prometastatic program mediated by interleukin 8 and the tumor microenvironment
Authors: Charlotte Rolny, Lorena Capparuccia, Andrea Casazza, Massimiliano Mazzone, Antonella Vallario, Alessandro Cignetti, Enzo Medico, Peter Carmeliet, Paolo M. Comoglio, Luca Tamagnone
Journal: The Journal of Experimental Medicine (2008)

Semaphorins are a large family of evolutionarily conserved morphogenetic molecules originally identified for their repelling role in axonal guidance. Intriguingly, semaphorins have recently been implicated in cancer progression (Neufeld, G., T. Lange, A. Varshavsky, and O. Kessler. 2007. Adv. Exp. Med. Biol. 600:118–131). In particular, semaphorin 3B (SEMA3B) is considered a putative tumor suppressor, and yet we found that it is expressed at high levels in many invasive and metastatic human cancers. By investigating experimental tumor models, we confirmed that SEMA3B expression inhibited tumor growth, whereas metastatic dissemination was surprisingly increased. We found that SEMA3B induced the production of interleukin (IL) 8 by tumor cells by activating the p38–mitogen-activated protein kinase pathway in a neuropilin 1–dependent manner. Silencing the expression of endogenous SEMA3B in tumor cells impaired IL-8 transcription. The release of IL-8, in turn, induced the recruitment of tumor-associated macrophages and metastatic dissemination to the lung, which could be rescued by blocking IL-8 with neutralizing antibodies. In conclusion, we report that SEMA3B exerts unexpected functions in cancer progression by fostering a prometastatic environment through elevated IL-8 secretion and recruitment of macrophages coupled to the suppression of tumor growth.
The Supraventricular Tachycardias
Authors: K Robinson, D Krikler
Journal: Annual Review of Medicine (1988)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Doxorubicin coupled to lactosaminated albumin inhibits the growth of hepatocellular carcinomas induced in rats by diethylnitrosamine
Authors: Luigi Fiume, Luigi Bolondi, Corrado Busi, Pasquale Chieco, Felix Kratz, Marcella Lanza, Alessandro Mattioli, Giuseppina Di Stefano
Journal: Journal of Hepatology (2005)
Derivation and Validation of a Renal Risk Score for People With Type 2 Diabetes
Authors: C. Raina Elley, Tom Robinson, Simon A. Moyes, Tim Kenealy, John Collins, Elizabeth Robinson, Brandon Orr-Walker, Paul L. Drury
Journal: Diabetes Care (2013)

Diabetes has become the leading cause of end-stage renal disease (ESRD). Renal risk stratification could assist in earlier identification and targeted prevention. This study aimed to derive risk models to predict ESRD events in type 2 diabetes in primary care.The nationwide derivation cohort included adults with type 2 diabetes from the New Zealand Diabetes Cohort Study initially assessed during 2000-2006 and followed until December 2010, excluding those with pre-existing ESRD. The outcome was fatal or nonfatal ESRD event (peritoneal dialysis or hemodialysis for ESRD, renal transplantation, or death from ESRD). Risk models were developed using Cox proportional hazards models, and their performance was assessed in a separate validation cohort.The derivation cohort included 25,736 individuals followed for up to 11 years (180,497 person-years; 86% followed for ≥5 years). At baseline, mean age was 62 years, median diabetes duration 5 years, and median HbA1c 7.2% (55 mmol/mol); 37% had albuminuria; and median estimated glomerular filtration rate (eGFR) was 77 mL/min/1.73 m2. There were 637 ESRD events (2.5%) during follow-up. Models that included sex, ethnicity, age, diabetes duration, albuminuria, serum creatinine, systolic blood pressure, HbA1c, smoking status, and previous cardiovascular disease status performed well with good discrimination and calibration in the derivation cohort and the validation cohort (n=5,877) (C-statistics 0.89-0.92), improving predictive performance compared with previous models.These 5-year renal risk models performed very well in two large primary care populations with type 2 diabetes. More accurate risk stratification could facilitate earlier intervention than using eGFR and/or albuminuria alone.
ImmunoCAP<sup>TM</sup> Phadiatop<sup>®</sup> Infant – a new blood test for detecting IgE sensitisation in children at 2 years of age
Authors: N. Ballardini, C. Nilsson, M. Nilsson, G. Lilja
Journal: Allergy (2005)

Background: Correct diagnosis of immunoglobulin E (IgE)‐mediated disease is the prerequisite for secondary allergy prevention during early childhood. Objective: To evaluate the diagnostic efficacy of a new blood test, Phadiatop ® Infant, in detecting IgE sensitisation to food and inhalant allergens among children at 2 years of age. Methods: Children ( n = 239) were followed prospectively from birth to 2 years of age for the presence of IgE sensitisation and the development of atopic manifestations. Immunoglobulin E sensitisation was evaluated by skin prick test (SPT) and analysis of allergen‐specific IgE antibodies in plasma to food and inhalant allergens. The children were classified into three groups: IgE‐sensitised, non‐IgE sensitised and inconclusive, depending on SPT and allergen‐specific IgE results. Results: Twenty‐six (11%) of the children were classified as IgE‐sensitised, 182 (76%) as non‐IgE sensitised and 31 (13%) as inconclusive. Phadiatop Infant was positive in 50 (21%) of the children. Ten children (4%) with identified IgE antibodies against the selected food and inhalant allergens showed negative Phadiatop Infant. Three children showed positive Phadiatop Infant but were negative in the other tests performed. These results correspond to positive and negative predictive values for Phadiatop Infant of 89 and 99%, respectively. Children with clinical symptoms of atopic diseases had significantly increased levels for Phadiatop Infant ( P &lt; 0.01). Conclusion: Phadiatop Infant appears to be a reliable alternative to SPT and the measurement of allergen‐specific IgE antibodies in plasma for detecting clinically important IgE sensitisation among children at 2 years of age.
Kidney Transplantation with Early Corticosteroid Withdrawal
Authors: Sapna P. Iyer, Lucas E. Nikkel, Kyle K. Nishiyama, Elzbieta Dworakowski, Serge Cremers, Chiyuan Zhang, Donald J. McMahon, Stephanie Boutroy, X. Sherry Liu, Lloyd E. Ratner, David J. Cohen, X. Edward Guo, Elizabeth Shane, Thomas L. Nickolas
Journal: Journal of the American Society of Nephrology (2014)

The use of early corticosteroid withdrawal (ECSW) protocols after kidney transplantation has become common, but the effects on fracture risk and bone quality are unclear. We enrolled 47 first-time adult transplant recipients managed with ECSW into a 1-year study to evaluate changes in bone mass, microarchitecture, biomechanical competence, and remodeling with dual energy x-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HRpQCT), parathyroid hormone (PTH) levels, and bone turnover markers obtained at baseline and 3, 6, and 12 months post-transplantation. Compared with baseline, 12-month areal bone mineral density by DXA did not change significantly at the spine and hip, but it declined significantly at the 1/3 and ultradistal radii (2.2% and 2.9%, respectively; both P<0.001). HRpQCT of the distal radius revealed declines in cortical area, density, and thickness (3.9%, 2.1%, and 3.1%, respectively; all P<0.001), trabecular density (4.4%; P<0.001), and stiffness and failure load (3.1% and 3.5%, respectively; both P<0.05). Findings were similar at the tibia. Increasing severity of hyperparathyroidism was associated with increased cortical losses. However, loss of trabecular bone and bone strength were most severe at the lowest and highest PTH levels. In summary, ECSW was associated with preservation of bone mineral density at the central skeleton; however, it was also associated with progressive declines in cortical and trabecular bone density at the peripheral skeleton. Cortical decreases related directly to PTH levels, whereas the relationship between PTH and trabecular bone decreases was bimodal. Studies are needed to determine whether pharmacologic agents that suppress PTH will prevent cortical and trabecular losses and post-transplant fractures.
Plasma fibronectin depletion enhances platelet aggregation and thrombus formation in mice lacking fibrinogen and von Willebrand factor
Authors: Adili Reheman, Hong Yang, Guangheng Zhu, Wuxun Jin, Feng He, Christopher M. Spring, Xufang Bai, Peter L. Gross, John Freedman, Heyu Ni
Journal: Blood (2008)
Expression in Hematological Malignancies of a Glucocorticoid Receptor Splice Variant That Augments Glucocorticoid Receptor-mediated Effects in Transfected Cells
Authors: Pieter de Lange, Christine M. Segeren, Jan W. Koper, Erik Wiemer, Pieter Sonneveld, Albert O. Brinkmann, Anne White, Iain J. Brogan, Frank H. de Jong, Steven W. J. Lamberts
Journal: Cancer Research (2001)

Glucocorticoids play an important role in the treatment of a number of hematological malignancies, such as multiple myeloma. The effects of glucocorticoids are mediated through the glucocorticoid receptor alpha, the abundance of which can be modulated by alternative splicing of the glucocorticoid receptor mRNA. Two splice variants of the glucocorticoid receptor mRNA have been described: glucocorticoid receptor beta, which reportedly has a dominant negative effect on the actions of the glucocorticoid receptor alpha, and glucocorticoid receptor P, of which the effects are unknown. In this study, we have investigated the expression levels of these two splice variants at the mRNA level in multiple myeloma cells and in a number of other hematological tumors. Although the glucocorticoid receptor beta mRNA was, if at all, expressed at very low levels, considerable amounts (up to 50% of the total glucocorticoid receptor mRNA) glucocorticoid receptor P mRNA was present in most hematological malignancies. In transient transfection studies in several cell types and in multiple myeloma cell lines, the glucocorticoid receptor P increased the activity of the glucocorticoid receptor alpha. These results suggest that the relative levels of the glucocorticoid receptor alpha and the glucocorticoid receptor P may play a role in the occurrence of glucocorticoid resistance in tumor cells during the treatment of hematological malignancies with glucocorticoids.
THE CAPSULES OR SHEATHS OF BACILLUS ACTINOIDES
Authors: Theobald Smith
Journal: The Journal of Experimental Medicine (1921)

The production of capsules or sheaths is subject to considerable variation in this species. Thus far coagulated serum has been found the only substrate to stimulate its appearance. It is not known whether the capsular substance is induced by the parasitism. The presence of sheaths within epithelial cells and their absence in cellular exudates suggest the inference that the sheath is a protective substance when the parasite multiplies in living cells. The complete absence of sheaths in some strains might make the recognition of this species difficult, but if its other characters both positive and negative are kept in mind, this difficulty will not be serious. Next in importance to fluctuations in the presence or absence of capsules is the change in metabolic processes leading to the production and accumulation of fatty substances in the cultures. The original capsular material resembles in its optical characters myelins. In the course of artificial cultivation fat granules make their appearance at the expense of the original myelin-like substance. This process may be regarded as a degenerative one in the sense that it accompanies the gradual loss of the function of secreting the capsular substance.
Taurine Supplementation Reduces Oxidative Stress and Improves Cardiovascular Function in an Iron-Overload Murine Model
Authors: Gavin Y. Oudit, Maria G. Trivieri, Neelam Khaper, Taneya Husain, Greg J. Wilson, Peter Liu, Michael J. Sole, Peter H. Backx
Journal: Circulation (2004)

Iron overload has an increasing worldwide prevalence and is associated with significant cardiovascular morbidity and mortality. Elevated iron levels in the myocardium lead to impaired systolic and diastolic function and elevated oxidative stress. Taurine accounts for 25% to 50% of the amino acid pool in myocardium, possesses antioxidant properties, and can inhibit L-type Ca2+ channels. Thus, we hypothesized that this agent would reduce the cardiovascular effects of iron overload.Iron-overloaded mice were generated by intraperitoneal injection of iron either chronically (5 days per week for 13 weeks) or subacutely (5 days per week for 4 weeks). Iron overload causes increased mortality, elevated oxidative stress, systolic and diastolic dysfunction, hypotension, and bradycardia. Taurine supplementation increased myocardial taurine levels by 45% and led to reductions in mortality and improved cardiac function, heart rate, and blood pressure in iron-overloaded mice. Histological examination of the myocardium revealed reduced apoptosis and interstitial fibrosis in iron-overloaded mice supplemented with taurine. Taurine mediated reduced oxidative stress in iron-overloaded mice along with attenuation of myocardial lipid peroxidation and protection of reduced glutathione level.These results demonstrate that treatment with taurine reduces iron-mediated myocardial oxidative stress, preserves cardiovascular function, and improves survival in iron-overloaded mice. The role of taurine in protecting reduced glutathione levels provides an important mechanism by which oxidative stress-induced myocardial damage can be curtailed. Taurine, as a dietary supplement, represents a potential new therapeutic agent to reduce the cardiovascular burden from iron-overload conditions.