tbuckley/cabot-search huggingface dataset:
Premature Ovarian Failure and Ovarian Autoimmunity*
Authors: A. Hoek, J. Schoemaker, H. A. Drexhage
Journal: Endocrine Reviews (1997)

Premature ovarian failure (POF) is defined as a syndrome characterized by menopause before the age of 40 yr. The patients suffer from anovulation and hypoestrogenism. Approximately 1% of women will experience menopause before the age of 40 yr. POF is a heterogeneous disorder with a multicausal pathogenesis involving chromosomal, genetic, enzymatic, infectious, and iatrogenic causes. There remains, however, a group of POF patients without a known etiology, the so-called "idiopathic" form. An autoimmune etiology is hypothesized for the POF cases with a concomitant Addison's disease and/or oöphoritis. It is concluded in this review that POF in association with adrenal autoimmunity and/or Addison's disease (2-10% of the idiopathic POF patients) is indeed an autoimmune disease. The following evidence warrants this view: 1) The presence of autoantibodies to steroid-producing cells in these patients; 2) The characterization of shared autoantigens between adrenal and ovarian steroid-producing cells; 3) The histological picture of the ovaries of such cases (lymphoplasmacellular infiltrate around steroid-producing cells); 4) The existence of various autoimmune animal models for this syndrome, which underlines the autoimmune nature of the disease. There is some circumstantial evidence for an autoimmune pathogenesis in idiopathic POF patients in the absence of adrenal autoimmunity or Addison's disease. Arguments in support of this are: 1) The presence of cellular immune abnormalities in this POF patient group reminiscent of endocrine autoimmune diseases such as IDDM, Graves' disease, and Addison's disease; 2) The more than normal association with IDDM and myasthenia gravis. Data on the presence of various ovarian autoantibodies and anti-receptor antibodies in these patients are, however, inconclusive and need further evaluation. A strong argument against an autoimmune pathogenesis of POF in these patients is the nearly absent histological confirmation (the presence of an oöphoritis) in these cases (< 3%). However, in animal models using ZP immunization, similar follicular depletion and fibrosis (as in the POF women) can be detected. Accepting the concept that POF is a heterogenous disorder in which some of the idiopathic forms are based on an abnormal self-recognition by the immune system will lead to new approaches in the treatment of infertility of these patients. There are already a few reports on a successful ovulation-inducing treatment of selected POF patients (those with other autoimmune phenomena) with immunomodulating therapies, such as high dosages of corticosteroids (288-292).
The three Rs: relicensing, recertification and revalidation
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2008)

By the time you read this I might be on holiday. I say ‘might’ because the organization of our family holiday, which is unwisely left to me, traditionally scores high marks for strategy but low marks on implementation. Incidentally, this is also the soundbite verdict on Lord Darzi's review of the NHS – and most other policy documents ever produced.
A Pharmacodynamic Study of Rapamycin in Men with Intermediate- to High-Risk Localized Prostate Cancer
Authors: Andrew J. Armstrong, George J. Netto, Michelle A. Rudek, Susan Halabi, David P. Wood, Patricia A. Creel, Kelly Mundy, S. Lindsay Davis, Ting Wang, Roula Albadine, Luciana Schultz, Alan W. Partin, Antonio Jimeno, Helen Fedor, Phillip G. Febbo, Daniel J. George, Robin Gurganus, Angelo M. De Marzo, Michael A. Carducci
Journal: Clinical Cancer Research (2010)

Given discrepancies between preclinical and clinical observations of mammalian target of rapamycin (mTOR) inhibition in prostate cancer, we sought to determine the pharmacodynamic effects of the mTOR/TORC1 inhibitor rapamycin in men with intermediate- to high-risk prostate cancer undergoing radical prostatectomy.Rapamycin was given at 3 or 6 mg orally for 14 days before radical prostatectomy in men with multifocal Gleason sum > or =7 prostate cancer; 10 untreated control subjects were included. The primary outcome was inhibition of phosphorylation of ribosomal S6 in posttreatment radical prostatectomy versus pretreatment biopsy tumor tissue, evaluated using a Simon two-stage design for pharmacodynamic efficacy.Thirty-two subjects were accrued: 20 at 3 mg, 2 at 6 mg, and 10 controls. No dose-limiting toxicities were observed at 3 mg; however, two of two men enrolled at 6 mg experienced dose-limiting toxicities including thrombocytopenia and fever with grade 3 stomatitis. Adverse events observed at 3 mg included stomatitis, rash, ileus, and neutropenia. Pharmacodynamic studies showed tumor S6 phosphorylation inhibition in 50% of 10 evaluable rapamycin-treated men with sufficient paired tissue [median 58% inhibition (P = 0.049) versus 2% inhibition in controls (P = 0.75)] with no significant effect on AKT activity. We observed no change in Ki-67 or caspase-3 cleavage but noted a reduction in cytoplasmic p27 staining with increased nuclear localization with rapamycin treatment. Prostate tissue rapamycin concentrations were 3- to 4-fold higher than blood.At 3 mg daily, rapamycin successfully and safely inhibited prostate cancer S6 phosphorylation and achieved relatively high prostate tissue concentrations. No effect on AKT phosphorylation, tumor proliferation, or apoptosis was observed.
Pulmonary Physiology and Pathophysiology: J B West. Lippincott Williams &amp; Wilkins, 2000. $31.95. ISBN 0 7817 2910 6
Authors: W Kinnear
Journal: Thorax (2002)

IL-5 in asthmaWe have recently published two manuscripts on the effects of interleukin (IL)-5 administration to patients with mild asthma in the American Journal of Respiratory & Critical Care Medicine 1 and in Thorax. 2 We are addressing this letter to the Editors of both journals.The data described in both papers have been obtained from one experiment performed in the same group of patients with mild asthma.While the paper in the American Journal of Respiratory & Critical Care Medicine reports primarily on the phenotypic changes in circulating blood eosinophils and CD34+ cells, the Thorax paper describes the changes in the airways with measurements of bronchial responsiveness and of eosinophil counts in sputum, together with eotaxin levels in the serum.Both manuscripts, however, detail the changes in blood eosinophil counts and serum
Asynchronous left ventricular diastolic filling in patients with isolated disease of the left anterior descending coronary artery: assessment with radionuclide ventriculography.
Authors: T Yamagishi, M Ozaki, T Kumada, T Ikezono, T Shimizu, Y Furutani, H Yamaoka, H Ogawa, M Matsuzaki, Y Matsuda
Journal: Circulation (1984)

To study the relationship between global and regional filling of the left ventricle, we conducted resting gated radionuclide ventriculographic studies in 15 control subjects (group 1) and 22 patients with isolated disease of the left anterior descending coronary artery (group 2). None had had a previous myocardial infarction. A computer program subdivided the image of the left ventricle into four regions. The time-activity and first-derivative curves of the global and regional left ventricles were computed. In the global left ventricle, the normalized peak filling rate (PFR) was decreased (p less than .01) and the ratio of the time to PFR (time interval from global end-systole to PFR) to the diastolic time, TPFR/DT, was greater (p less than .02) in group 2 than in group 1. In the regional left ventricle, in the side perfused by the stenosed vessel (septal and apical), PFR was slightly decreased in the apical (p less than .05), but not the septal region (p = NS); TPFR/DT was greater in the apical (p less than .02) and in the septal region (p less than .01) in group 2. In the normally perfused lateral side, there were no significant differences in PFR or in TPFR/DT between group 1 and group 2. Total delta t/DT, which was defined as the ratio of the sum of the absolute values of the time differences from global PFR to regional PFR (septal, apical, and lateral) to the diastolic time, was significantly greater in group 2 (0.09 +/- 0.05 vs 0.16 +/- 0.05; p less than .001). This indicates the existence of asynchronous diastolic filling in the different regions of the left ventricle in group 2. A negative correlation existed between total delta t/DT and global PFR (r = -.64, p less than .001). Thus, in patients with one-vessel disease, asynchronous diastolic filling occurs due to the filling disturbance in the affected regions, which may cause impairment of the filling of the global left ventricle.
Management of the HIV-HCV coinfected patient
Authors: D MUTIMER
Journal: Gut (2000)

See article on page 694 

Parenterally acquired infection by human immunodeficiency virus (HIV) is frequently associated with chronic hepatitis C virus (HCV) infection. Last year, the European Association for the Study of the Liver (EASL) released a consensus statement including guidelines for the management of HCV infection.1 Concerning the antiviral treatment of HCV in HIV coinfected patients, the guidelines suggested that treatment may be indicated in those patients in whom treatment has stabilised the HIV infection . Certainly, recent improvement in the antiviral treatment of each of these infections demands a reappraisal of the management of the HIV-HCV coinfected patient.

The study of Zylerberg and colleagues2 in this issue of Gut addresses one aspect of this problem—that is, the treatment of HCV during concurrent antiretroviral therapy (see page 694). The study cohort comprised 21 coinfected patients whose anti-HIV treatment included zidovudine, stavudine, and a protease inhibitor. HCV infection was treated with α interferon and ribavirin, a combination that has an established role for treatment of selected immunocompetent patients with HCV infection.3 The study concludes that combination therapy of HCV infection can be safely given …
Inflammatory Responses Induced by the Filarial Nematode <i>Brugia malayi</i> Are Mediated by Lipopolysaccharide-like Activity from Endosymbiotic <i>Wolbachia</i> Bacteria
Authors: Mark J. Taylor, Helen F. Cross, Katja Bilo
Journal: The Journal of Experimental Medicine (2000)

The pathogenesis of filarial disease is characterized by acute and chronic inflammation. Inflammatory responses are thought to be generated by either the parasite, the immune response, or opportunistic infection. We show that soluble extracts of the human filarial parasite Brugia malayi can induce potent inflammatory responses, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and nitric oxide (NO) from macrophages. The active component is heat stable, reacts positively in the Limulus amebocyte lysate assay, and can be inhibited by polymyxin B. TNF-α, IL-1β, and NO responses were not induced in macrophages from lipopolysaccharide (LPS)-nonresponsive C3H/HeJ mice. The production of TNF-α after chemotherapy of microfilariae was also only detected in LPS-responsive C3H/HeN mice, suggesting that signaling through the Toll-like receptor 4 (TLR4) is necessary for these responses. We also show that CD14 is required for optimal TNF-α responses at low concentrations. Together, these results suggest that extracts of B. malayi contain bacterial LPS. Extracts from the rodent filaria, Acanthocheilonema viteae, which is not infected with the endosymbiotic Wolbachia bacteria found in the majority of filarial parasites, failed to induce any inflammatory responses from macrophages, suggesting that the source of bacterial LPS in extracts of B. malayi is the Wolbachia endosymbiont. Wolbachia extracts derived from a mosquito cell line induced similar LPS-dependent TNF-α and NO responses from C3H/HeN macrophages, which were eliminated after tetracycline treatment of the bacteria. Thus, Wolbachia LPS may be one of the major mediators of inflammatory pathogenesis in filarial nematode disease.
Comparison of Changes in Physical Self-Concept, Global Self-Esteem, Depression and Anxiety following Two Different Psychomotor Therapy Programs in Nonpsychotic Psychiatric Inpatients
Authors: Jan Knapen, Peter van de Vliet, Herman van Coppenolle, Ans David, Joseph Peuskens, Guido Pieters, Koen Knapen
Journal: Psychotherapy and Psychosomatics (2005)

The first objective of this study was to compare the changes in physical self-concept, global self-esteem, depression and anxiety after participation in one of two 16-week psychomotor therapy programs for nonpsychotic psychiatric inpatients. The second objective was to study the relationship between changes in these variables.One hundred and ninety-nine inpatients were randomly assigned to either a personalized psychomotor fitness program, consisting of aerobic exercise and weight training, or a general program of psychomotor therapy, consisting of different forms of physical exercises and relaxation training. Physical self-concept was evaluated using the Dutch version of the Physical Self-Perception Profile at baseline, after 8 weeks, and after completion of the 16-week interventions. At the same time points, additional variables of global self-esteem, depression and anxiety were assessed by means of the Rosenberg Self-Esteem Inventory, the Beck Depression Inventory and the Trait Anxiety Inventory, respectively.After 16 weeks, both groups showed significant improvements in all outcome measures (p values ranged from 0.01 to < 0.0001), with no between-group differences. In both groups, the improvement in physical self-concept was correlated with increased global self-esteem and decreased depression and anxiety levels (p < 0.01).The results suggest that both psychomotor therapy programs are equally effective in enhancing physical self-concept. The relationship between improvements in physical self-concept and enhancements in global self-esteem, depression and anxiety supports the potential role of the physical self-concept in the recovery process of depressed and anxious psychiatric inpatients.
Type I collagen degradation does not diminish with RA disease duration
Authors: M Hakala
Journal: Annals of the Rheumatic Diseases (2001)

To assess the relation between type I collagen degradation and the duration of rheumatoid arthritis (RA).The serum concentrations of cross linked carboxyterminal telopeptide of type I collagen (ICTP) measured earlier in a community based series (90 patients) and a hospital based series (59 patients) were re-evaluated with reference to the duration of RA.The serum ICTP showed a positive correlation with the duration of the disease in the hospital based series (r(s)=0.40, p<0.01) but not in the community based one (r(s)=0.18, p=0.10).Type I collagen degradation predominantly reflecting pathological bone destruction does not seem to diminish in longlasting RA.
Methotrexate toxicity precipitated by azapropazone
Authors: HELENA M. DALY, G.L. SCOTT, J. BOYLE, C.J.C. ROBERTS
Journal: British Journal of Dermatology (1986)

We report an episode of bone marrow hypoplasia following the administration of azapropazone to a patient stabilized on regular methotrexate for psoriasis. A pharmacokinetic interaction is postulated.
Colon Cancer Survival Is Associated With Increasing Number of Lymph Nodes Analyzed: A Secondary Survey of Intergroup Trial INT-0089
Authors: T.E. Le Voyer, E.R. Sigurdson, A.L. Hanlon, R.J. Mayer, J.S. Macdonald, P.J. Catalano, D.G. Haller
Journal: Journal of Clinical Oncology (2003)

To determine the relationship, in patients with adenocarcinoma of the colon, between survival and the number of lymph nodes analyzed from surgical specimens.Intergroup Trial INT-0089 is a mature trial of adjuvant chemotherapy for high-risk patients with stage II and stage III colon cancer. We performed a secondary analysis of this group with overall survival (OS) as the main end point. Cause-specific survival (CSS) and disease-free survival were secondary end points. Rates for these outcome measures were estimated using Kaplan-Meier methodology. Log-rank test was used to compare overall curves, and Cox proportional hazards regression was used to multivariately assess predictors of outcome.The median number of lymph nodes removed at colectomy was 11 (range, one to 87). Of the 3411 assessable patients, 648 had no evidence of lymph node metastasis. Multivariate analyses were performed on the node-positive and node-negative groups separately to ascertain the effect of lymph node removal. Survival decreased with increasing number of lymph node involvement (P =.0001 for all three survival end points). After controlling for the number of nodes involved, survival increased as more nodes were analyzed (P =.0001 for all three end points). Even when no nodes were involved, OS and CSS improved as more lymph nodes were analyzed (P =.0005 and P =.007, respectively).The number of lymph nodes analyzed for staging colon cancers is, itself, a prognostic variable on outcome. The impact of this variable is such that it may be an important variable to include in evaluating future trials.
TRAC Variants Associate with IgA Nephropathy
Authors: Ru Li, Chao Xue, Caixia Li, Tanqi Lou, Yu Tao, Youji Li, Weijun Huang, Jun Zhang, Joseph C. K. Leung, Man F. Lam, Tim J. Vyse, Kar N. Lai, Changyou Wu, Yiming Wang
Journal: Journal of the American Society of Nephrology (2009)

The T cell receptor alpha constant gene (TRAC) encodes the constant region of the alpha chain for the T cell receptor, and the association of its gene variants with IgA nephropathy remains controversial. The authors resequenced the gene in 100 patients with IgA nephropathy and 100 controls, tested its linkage disequilibrium pattern, constructed haplotypes, and performed association and functional studies. First, the association between TRAC variants and IgA nephropathy was tested in 704 patients and 704 controls. Next, these 704 patients were divided into two independent datasets--310 with family member(s) and 394 single patients--to test the association separately. Results showed that the gene is located in a recombination hot spot, with nine linkage disequilibrium blocks within a 6.9-kb region. There is a hypervariable region with six single-nucleotide polymorphisms (SNPs) in an 85-bp stretch in intron 1. We identified multiple SNPs and two haplotypes that associate with IgA nephropathy (P = 0.0000013-0.0096 by logistic regression for SNPs; P = 0.0003 and P = 0.0398 for haplotype associations). The family-based study replicated both haplotype findings, and the 394 single-patient case-control study replicated the association with haplotype 1 (P = 0.0033). The overtransmitted/observed haplotypes demonstrated reduced transcription activity compared with the undertransmitted/observed haplotypes. In conclusion, this study suggests an association between TRAC variants and susceptibility to IgA nephropathy.
Thyroid hormone modulation of glucocorticoid-induced polycystic kidney disease.
Authors: J F Crocker, M E Schenk, D A Hamilton, D E Cole, A T McDonald, P D Acott
Journal: Journal of the American Society of Nephrology (1996)

Crocker, J F; Schenk, M E; Hamilton, D A; Cole, D E; McDonald, A T; Acott, P D Author Information
Effect of Supervised Progressive Resistance-Exercise Training Protocol on Insulin Sensitivity, Glycemia, Lipids, and Body Composition in Asian Indians With Type 2 Diabetes
Authors: Anoop Misra, Narendra K. Alappan, Naval K. Vikram, Kashish Goel, Nidhi Gupta, Kanchan Mittal, Suryaprakash Bhatt, Kalpana Luthra
Journal: Diabetes Care (2008)

To evaluate the effect of supervised progressive resistance-exercise training (PRT) protocol on insulin sensitivity, glycemia (blood glucose and A1C levels), lipids, and body composition in Asian Indians with type 2 diabetes.Thirty patients with type 2 diabetes underwent 12 weeks of PRT of six muscle groups (two sets, 10 repetitions each). The subjects were evaluated with detailed anthropometry and with measurements of the disappearance of glucose per unit time (K) during the short insulin tolerance test (K(ITT)) for assessment of insulin sensitivity; of fasting blood glucose, A1C, lipids, and high-sensitivity C-reactive protein (hsCRP); of total body fat, regional fat, and lean body mass by dual-energy X-ray absorptiometry; and of cross-sectional skeletal muscle area of upper arm and thigh by computed tomography scan.Insulin sensitivity improved significantly from mean +/- SD K(ITT) 1.22 +/- 0.73 to 2.13 +/- 0.75 (P < 0.0001) after the intervention. Significant decline (mean difference +/- SD) from baseline was recorded in levels of the following parameters: A1C (0.54 +/- 0.4%, P < 0.001), fasting blood glucose (2.7 +/- 2.2 mmol/l, P < 0.001), total cholesterol (0.39 +/- 0.7 mmol/l, P = 0.003), serum triglycerides (0.39 +/- 0.5 mmol/l, P < 0.001), and truncal and peripheral subcutaneous adipose tissue compartments (SCAT) (P < 0.001). However, no significant changes were noticed in BMI or levels of total body fat, truncal fat, lean body mass, cross-sectional skeletal muscle area of the extremities, or hsCRP levels.Moderate-intensity PRT for 3 months resulted in significant improvement in insulin sensitivity, glycemia, lipids, and truncal and peripheral SCAT in patients with type 2 diabetes. Resistance training should be an integral part of exercise regimen in Asian Indians with type 2 diabetes.
Extrarenal Vitamin D Activation and Interactions Between Vitamin D<sub>2</sub>, Vitamin D<sub>3</sub>, and Vitamin D Analogs
Authors: Glenville Jones
Journal: Annual Review of Nutrition (2013)

Our understanding of the mechanism of action of vitamin D has been broadened by the discovery of the extrarenal 1α-hydroxylase (CYP27B1) in various vitamin D target tissues around the body and the implications of this for the putative paracrine actions of 1α,25-dihydroxyvitamin D₃. This review updates our current knowledge of the cytochrome P450-mediated steps of vitamin D activation (CYP2R1, CYP27B1) and inactivation (CYP24A1, CYP3A4) and the newest physiological roles of vitamin D. The review goes on to examine how well exogenously supplied vitamin D compounds, whether dietary vitamin D₂ supplements or prescribed vitamin D analogs, substitute for their natural counterparts; how in some cases vitamin D can be used in conjunction with vitamin D analogs; and the overall impact of these supplements and drugs on the components of the vitamin D signal transduction machinery.
The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification
Authors: Daniel C. Cattran, Rosanna Coppo, H. Terence Cook, John Feehally, Ian S.D. Roberts, Stéphan Troyanov, Charles E. Alpers, Alessandro Amore, Jonathan Barratt, Francois Berthoux, Stephen Bonsib, Jan A. Bruijn, Vivette D'Agati, Giuseppe D'Amico, Steven Emancipator, Francesco Emma, Franco Ferrario, Fernando C. Fervenza, Sandrine Florquin, Agnes Fogo, Colin C. Geddes, Hermann-Josef Groene, Mark Haas, Andrew M. Herzenberg, Prue A. Hill, Ronald J. Hogg, Stephen I. Hsu, J. Charles Jennette, Kensuke Joh, Bruce A. Julian, Tetsuya Kawamura, Fernand M. Lai, Chi Bon Leung, Lei-Shi Li, Philip K.T. Li, Zhi-Hong Liu, Bruce Mackinnon, Sergio Mezzano, F. Paolo Schena, Yasuhiko Tomino, Patrick D. Walker, Haiyan Wang, Jan J. Weening, Nori Yoshikawa, Hong Zhang
Journal: Kidney International (2009)
The Okinawa Screening Program
Authors: Kunitoshi Iseki
Journal: Journal of the American Society of Nephrology (2003)

Predictors of ESRD were identified using independent registries of both ESRD patients and the general population in Okinawa, Japan. Besides male gender, we found that the significant predictors of ESRD to be proteinuria, hematuria, and hypertension, especially diastolic BP. Among the laboratory findings, a high serum creatinine level was shown to be a strong predictor of ESRD. The effects of age, obesity, and hypercholesterolemia were insignificant, but this needs to be confirmed in a larger cohort and other registries.
299 SPONTANEOUS BACTERIAL PERITONITIS (SBP) PROPHYLAXIS: A RANDOMISED CONTROLLED TRIAL COMPARING TRIMETHOPRIM-SULFAMETHOXAZOLE AND NORFLOXACIN
Authors: S. Lontos, P.J. Gow, S.K. Roberts, R.B. Vaughan, P.W. Angus
Journal: Journal of Hepatology (2008)