tbuckley/cabot-search huggingface dataset:
Does Hypoadiponectinemia Explain the Increased Risk of Diabetes and Cardiovascular Disease in South Asians?
Authors: Ravi Retnakaran, Anthony J.G. Hanley, Bernard Zinman
Journal: Diabetes Care (2006)

A substantial body of evidence has documented the high prevalence of type 2 diabetes and cardiovascular disease (CVD) among people of South-Asian descent, defined on the basis of ancestral origin from the Indian subcontinent comprised of India, Pakistan, Bangladesh, and Sri Lanka (1–7). These observations relate to both native South Asians in urban settings and those living overseas in different countries (including the U.K., Canada, the U.S., South Africa, Singapore, Fiji, and Trinidad), leading to the suggestion that members of this ethnic group may share an underlying predisposition to metabolic and vascular disease (3,4,6–10). It has been postulated that a gene-environment interaction between underlying genetic susceptibility and urbanization-induced lifestyle changes (such as increased caloric intake and decreased energy expenditure) may promote the clinical expression of a high-risk phenotype (7). Clinically, this phenomenon translates to a 1.5- to 10-fold–higher incidence of coronary artery disease (CAD) in immigrant South Asians compared with the general populations of the host countries (2–4,10,11). Furthermore, South Asians exhibit clinical features suggestive of a distinctly aggressive cardiovascular pathophysiology compared with other ethnic groups. These features include significantly higher cardiovascular mortality (4,12) and earlier onset of CAD in young adults (7,13). Thus, identification of the determinants of vascular disease in South Asians may be relevant to both 1 ) our understanding of the pathophysiology of CVD and 2 ) preventive health care for the approximately one-fifth of the world’s population that comes from the Indian subcontinent.

A similarly worrisome problem is the rising prevalence of type 2 diabetes in South Asians. India currently has the highest number of cases of diabetes in the world (14). In addition, it has been projected that between 2000 and 2030, the number of patients with diabetes …
Regulation and expression of <scp>IL</scp>‐32 in chronic rhinosinusitis
Authors: M. B. Soyka, A. Treis, T. Eiwegger, G. Menz, S. Zhang, D. Holzmann, C. A. Akdis, N. Meyer
Journal: Allergy (2012)

Abstract Background Activated T lymphocytes and their interaction with resident tissue cells, particularly epithelium, play important roles in inflammatory processes in chronic rhinosinusitis ( CRS ). IL ‐32 is a recently described cytokine, which is expressed in a variety of tissue cells and involved in the pathogenesis of several chronic inflammatory diseases. Methods Human sinus epithelial cells were isolated from biopsies and stimulated with different cytokines, which play a role in the pathogenesis of CRS . IL ‐32 mRNA expression was analyzed using real‐time‐ PCR , IL ‐32 protein was determined by W estern blot and flow cytometry as well as immunofluorescent staining in primary sinus epithelial cells and nasal biopsies from patients with CRS and healthy controls. Results IL ‐32 mRNA was upregulated by TNF ‐α and IFN ‐γ in primary sinus epithelial cells, whereas IL ‐1 β, IL ‐4, IL ‐13, and IL ‐17 did not influence IL ‐32 expression. IL ‐32 mRNA expression was significantly higher in human primary sinonasal epithelial cells ( HSEC s) cocultured with Th1 cells compared with HSEC s cocultured with T h0 or T h2 cells. IL ‐32 mRNA expression was significantly higher in biopsies from sinus epithelial tissue of CRS patients with nasal polyps compared with healthy subjects ( P = 0.01). IL ‐32 was detected in biopsies from patients with CRS , whereas it was scarcely present in control tissues. Conclusion The induction of IL ‐32 by TNF ‐α, IFN ‐γ and T h1 cells as well as its increased expression in sinus tissues from CRS patients with nasal polyps demonstrated a potential role for IL ‐32 in the pathogenesis of CRS .
The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: Proposal for an Evidence-Based Stage Classification System for the Forthcoming (8th) Edition of the TNM Classification of Malignant Tumors
Authors: Frank C. Detterbeck, Kelly Stratton, Dorothy Giroux, Hisao Asamura, John Crowley, Conrad Falkson, Pier Luigi Filosso, Aletta A. Frazier, Giuseppe Giaccone, James Huang, Jhingook Kim, Kazuya Kondo, Marco Lucchi, Mirella Marino, Edith M. Marom, Andrew G. Nicholson, Meinoshin Okumura, Enrico Ruffini, Paul Van Schil
Journal: Journal of Thoracic Oncology (2014)
Multicenter randomized phase III study of the cardioprotective effect of dexrazoxane (Cardioxane®) in advanced/metastatic breast cancer patients treated with anthracycline-based chemotherapy
Authors: M. Marty, M. Espié, A. Llombart, A. Monnier, B.L. Rapoport, V. Stahalova
Journal: Annals of Oncology (2006)
Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study
Authors: Federico Cappuzzo, Tudor Ciuleanu, Lilia Stelmakh, Saulius Cicenas, Aleksandra Szczésna, Erzsébet Juhász, Emilio Esteban, Olivier Molinier, Wolfram Brugger, Ivan Melezínek, Gaëlle Klingelschmitt, Barbara Klughammer, Giuseppe Giaccone
Journal: The Lancet Oncology (2010)
The airway microvasculature and exercise induced asthma.
Authors: S D Anderson, E Daviskas
Journal: Thorax (1992)

It has been proposed that exercise induced asthma is a result of "rapid expansion of the blood volume of peribronchial plexi" (McFadden ER, Lancet 1990;335:880-3). This hypothesis proposes that the development of exercise induced asthma depends on the thermal gradient in the airways at the end of hyperpnoea. The events that result in exercise induced asthma are vasoconstriction and airway cooling followed by reactive hyperaemia. We agree that the airway microcirculation has the potential for contributing to the pathophysiology of exercise induced asthma. We do, however, question whether reactive hyperaemia, in response to airway cooling, is the mechanism whereby hyperpnoea provokes airways obstruction in asthmatic patients. Further, we question whether vasoconstriction accompanies dry air breathing and whether an abnormal temperature gradient and rapid rewarming of the airways are prerequisites for exercise induced asthma. From published experiments we conclude that dry air breathing is associated with vasodilation and increase in airway blood flow rather than vasoconstriction and a decrease in blood flow to the airways. We propose that the stimulus for the increase in airway blood flow is an increase in osmolarity of the airway submucosa. This osmotic change is caused by the movement of water to the airway lumen in response to evaporative water loss during hyperpnoea. The increase in airway blood flow may occur directly or indirectly by the osmotic release of mediators. Exercise induced asthma is most likely to be due to the contraction of bronchial smooth muscle caused by the same mediators. Whether it is enhanced or inhibited by alterations in airway blood flow is not yet established in man.
Absence of biologically important Kaposi sarcoma–associated herpesvirus gene products and virus-specific cellular immune responses in multiple myeloma
Authors: Christian Brander, Noopur Raje, Paula G. O'Connor, Faith Davies, Jennifer Davis, Darminder Chauhan, Teru Hideshima, Jeff Martin, Dennis Osmond, Dean H. Kedes, Bruce D. Walker, David T. Scadden, Kenneth C. Anderson
Journal: Blood (2002)
Cost-Effectiveness of Preventing Loss to Follow-up in HIV Treatment Programs: A Côte d'Ivoire Appraisal
Authors: Elena Losina, Hapsatou Touré, Lauren M. Uhler, Xavier Anglaret, A. David Paltiel, Eric Balestre, Rochelle P. Walensky, Eugène Messou, Milton C. Weinstein, François Dabis, Kenneth A. Freedberg
Journal: PLoS Medicine (2009)

Data from HIV treatment programs in resource-limited settings show extensive rates of loss to follow-up (LTFU) ranging from 5% to 40% within 6 mo of antiretroviral therapy (ART) initiation. Our objective was to project the clinical impact and cost-effectiveness of interventions to prevent LTFU from HIV care in West Africa.
Androgen Deprivation as a Strategy for Prostate Cancer Chemoprevention
Authors: J. W. Aquilina, J. J. Lipsky, D. G. Bostwick
Journal: JNCI Journal of the National Cancer Institute (1997)

Why Androgen Deprivation?The prostate gland requires androgens for proper growth, maintenance, and function.Men with 5␣-reductase deficiency (21,22) and men castrated when young (eunuchs) do not develop prostate cancer (23).
The Temporal Lag Structure of Short-term Associations of Fine Particulate Matter Chemical Constituents and Cardiovascular and Respiratory Hospitalizations
Authors: Sun-Young Kim, Jennifer L Peel, Michael P Hannigan, Steven J Dutton, Lianne Sheppard, Maggie L Clark, Sverre Vedal
Journal: Environmental Health Perspectives (2012)

Background: In air pollution time-series studies, the temporal pattern of the association of fine particulate matter (PM2.5; particulate matter ≤ 2.5 µm in aerodynamic diameter) and health end points has been observed to vary by disease category. The lag pattern of PM2.5 chemical constituents has not been well investigated, largely because daily data have not been available.Objectives: We explored the lag structure for hospital admissions using daily PM2.5 chemical constituent data for 5 years in the Denver Aerosol Sources and Health (DASH) study.Methods: We measured PM2.5 constituents, including elemental carbon, organic carbon, sulfate, and nitrate, at a central residential site from 2003 through 2007 and linked these daily pollution data to daily hospital admission counts in the five-county Denver metropolitan area. Total hospital admissions and subcategories of respiratory and cardiovascular admissions were examined. We assessed the lag structure of relative risks (RRs) of hospital admissions for PM2.5 and four constituents on the same day and from 1 to 14 previous days from a constrained distributed lag model; we adjusted for temperature, humidity, longer-term temporal trends, and day of week using a generalized additive model.Results: RRs were generally larger at shorter lags for total cardiovascular admissions but at longer lags for total respiratory admissions. The delayed lag pattern was particularly prominent for asthma. Elemental and organic carbon generally showed more immediate patterns, whereas sulfate and nitrate showed delayed patterns.Conclusion: In general, PM2.5 chemical constituents were found to have more immediate estimated effects on cardiovascular diseases and more delayed estimated effects on respiratory diseases, depending somewhat on the constituent.
Drug–Induced Hepatitis Associated With Anticytoplasmic Organelle Autoantibodies
Authors: Jean-Claude Homberg, Nielsen Abuaf, Samir Helmy-Khalil, Michel Biour, Raoul Poupon, Shamsul Islam, François Darnis, Victor Georges Levy, Pierre Opolon, Michel Beaugrand, Jacques Toulet, Gaby Danan, Jean-Pierre Benhamou
Journal: Hepatology (1985)

A study from five hepatology units documenting 157 cases of drug-induced hepatitis and a second study from a laboratory of immunology which tested more than 100,000 sera permitted us to establish the frequency of antiorganelle antibodies and their diagnostic value in drug-induced hepatitis. In drug-induced hepatitis caused by a heterogenous group of drugs consisting of ajmaline, aminopterine, isaxonine, isoniazid, perhexiline, phenylbutazone and troleandromycine, antiorganelle antibodies were absent or rare. In drug-induced hepatitis caused by another heterogenous group of drugs, including clometacin, fenofibrate, oxyphenisatin and papaverine, antismooth muscle, antinucleus and antimitochondria antibodies were found in isolation or in different combinations in 70% of cases. From the presence of antismooth muscle antibodies in sera, we could trace 30 cases of clometacin-induced hepatitis. The third group included drug-induced hepatitis with special antibody:iproniazid-induced hepatitis with antimitochondrial antibody 6 and tienilic acid (ticrynafen)-induced hepatitis with antiliver/kidney microsome antibody 2 (anti-LKM2). These two antibodies are rare in routine sera and were absent in patients who received the drug and had no liver damage. From the presence of corresponding antibodies, we detected six cases of iproniazid-induced hepatitis and 67 cases of tienilic acid-induced hepatitis. Antiorganelle antibodies found in high titers disappeared in 2 to 24 months following withdrawal of the offending drug. The fourth group was represented by halothane-induced hepatitis; antiliver/kidney microsome antibody 1 was weak and infrequent. Similarities between drug-induced hepatitis of the second group and lupoïd hepatitis suggest that drugs may reveal this spontaneous disorder.(ABSTRACT TRUNCATED AT 250 WORDS)
Baseline serum RANKL levels may serve to predict remission in rheumatoid arthritis patients treated with TNF antagonists
Authors: I. Gonzalez-Alvaro, A. M Ortiz, E. G Tomero, A. Balsa, J. Orte, A. Laffon, R. Garcia-Vicuna
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Aims:</h3> The objective of this study was to investigate whether baseline receptor activator for nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) serum (s) levels can predict the therapeutic response to TNF antagonists (a-TNF). <h3>Methods:</h3> We studied 75 rheumatoid arthritis patients (81% female) with a longstanding refractory disease. The variables of disease activity, physical function and sRANKL and sOPG levels were determined before and after both 12–14 and 28–30 weeks of a-TNF therapy (65 adalimumab, 10 infliximab). Remission was defined by a 28 joint count disease activity score (DAS28) ⩽2.6 and clinical response by a reduction in DAS28⩾1.2 at both 3- and 7-month follow-up visits. <h3>Results:</h3> In most patients, disease activity was severe, as reflected by a baseline DAS28 score of 5.9±1 (mean±SD), an HAQ of 1.6 (1.1 to 2.1) (median (interquartile range (IQR))) and a CRP 15 mg/l (IQR: 9 to 24). The sRANKL levels and RANKL/OPG ratio in patients that achieved remission were significantly lower at baseline than in the remaining patients at both 3 and 7 months of follow-up. The sOPG levels correlated with the HAQ and the physician's disease assessment and diminished significantly after a-TNF treatment. However, no significant association was detected between the therapeutic response profile and sOPG levels. <h3>Conclusions:</h3> These data suggest that in patients receiving a-TNF treatment, lower serum levels of RANKL and RANKL/OPG ratio may serve to predict remission.
Apopain/CPP32 cleaves proteins that are essential for cellular repair: a fundamental principle of apoptotic death.
Authors: L Casciola-Rosen, D W Nicholson, T Chong, K R Rowan, N A Thornberry, D K Miller, A Rosen
Journal: The Journal of Experimental Medicine (1996)

Proteolysis mediated by the interleukin 1 beta-converting enzyme (ICE) homologues is an important mechanism of the apoptotic process. The ICE homologue apopain/CPP-32/Yama (subsequently referred to as apopain) cleaves poly(ADP-ribose)polymerase (PARP) early during apoptosis. Additional apoptosis-specific protein cleavages have been observed in which the direct involvement of ICE-like proteases has been postulated. These substrates include the 70-kD protein component of the U1-ribonucleoprotein (U1-70kD), and the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs). The present studies demonstrate that U1-70kD and DNA-PKcs are excellent substrates for apopain, with cleavage occurring at sites that are highly similar to the cleavage site within PARP. The fragments generated from isolated protein substrates by apopain are identical to those observed in intact apoptotic cells, in apoptotic cell extracts, and in normal cell extracts to which apopain has been added. Like PARP, cleavage of these substrates in apoptotic cell extracts is abolished by nanomolar concentrations of Ac-DEVD-CHO and micromolar amounts of Ac-YVAD-CHO, confirming the involvement of apopain or an apopain-like activity. We propose that a central function of apopain or similar homologues in apoptosis is the cleavage of nuclear repair proteins, thereby abolishing their critical homeostatic functions.
Comprehensive Pharmacogenetic Analysis of Irinotecan Neutropenia and Pharmacokinetics
Authors: Federico Innocenti, Deanna L. Kroetz, Erin Schuetz, M. Eileen Dolan, Jacqueline Ramírez, Mary Relling, Peixian Chen, Soma Das, Gary L. Rosner, Mark J. Ratain
Journal: Journal of Clinical Oncology (2009)

Purpose We aim to identify genetic variation, in addition to the UGT1A1*28 polymorphism, that can explain the variability in irinotecan (CPT-11) pharmacokinetics and neutropenia in cancer patients. Patients and Methods Pharmacokinetic, genetic, and clinical data were obtained from 85 advanced cancer patients treated with single-agent CPT-11 every 3 weeks at doses of 300 mg/m 2 (n = 20) and 350 mg/m 2 (n = 65). Forty-two common variants were genotyped in 12 candidate genes of the CPT-11 pathway using several methodologies. Univariate and multivariate models of absolute neutrophil count (ANC) nadir and pharmacokinetic parameters were evaluated. Results Almost 50% of the variation in ANC nadir is explained by UGT1A1*93, ABCC1 IVS11 –48C&gt;T, SLCO1B1*1b, ANC baseline levels, sex, and race (P &lt; .0001). More than 40% of the variation in CPT-11 area under the curve (AUC) is explained by ABCC2 –24C&gt;T, SLCO1B1*5, HNF1A 79A&gt;C, age, and CPT-11 dose (P &lt; .0001). Almost 30% of the variability in SN-38 (the active metabolite of CPT-11) AUC is explained by ABCC1 1684T&gt;C, ABCB1 IVS9 –44A&gt;G, and UGT1A1*93 (P = .004). Other models explained 17%, 23%, and 27% of the variation in APC (a metabolite of CPT-11), SN-38 glucuronide (SN-38G), and SN-38G/SN-38 AUCs, respectively. When tested in univariate models, pretreatment total bilirubin was able to modify the existing associations between genotypes and phenotypes. Conclusion On the basis of this exploratory analysis, common polymorphisms in genes encoding for ABC and SLC transporters may have a significant impact on the pharmacokinetics and pharmacodynamics of CPT-11. Confirmatory studies are required.
Initial experience with routine administration of etanercept in psoriasis
Authors: M. De Groot, M. Appelman, P.I. Spuls, M.A. De Rie, J.D. Bos
Journal: British Journal of Dermatology (2006)

Etanercept and efalizumab recently became available and reimbursed for routine use in severe psoriasis in the Netherlands. The criteria for reimbursement are Psoriasis Area and Severity Index (PASI) > or = 10 (or Skindex-29 > or = 35 if PASI > or = 8 and < 10) and ineffectiveness of ultraviolet (UV) B/psoralen plus UVA, methotrexate and ciclosporin, or a contraindication to or serious side-effect(s) during these treatments.We hypothesized: (i) that efficacy would be lower than that obtained in published phase II and III studies because (a) resistance to all conventional therapies as a reimbursement condition would select for more resistant cases and (b) inclusion would be more restricted to severe cases (higher PASI), and (ii) that efficacy would be lower in obese patients due to the possible role of adipose tissue in tumour necrosis factor (TNF)-alpha homeostasis.We treated 50 patients (38 men, 12 women; mean PASI 15.8) with etanercept 25 mg or 50 mg twice weekly and evaluated in a retrospective analysis the efficacy and safety in comparison with data from published trials. Additionally, we related the clinical effect to the body mass index (BMI), for adipose tissue is thought to have a possible role in TNF-alpha homeostasis.Based on the literature, 30% and 49% of the patients treated with etanercept 25 mg and 50 mg twice weekly, respectively, should have achieved 75% or more improvement in PASI compared with baseline (PASI 75), and 10% and 21%, respectively, should have achieved 90% or more improvement (PASI 90). Our data showed that 21% in the 2 x 25 mg group and 23% in the 2 x 50 mg group achieved PASI 75. PASI 90 was only attained in 7% of patients treated with 2 x 25 mg and 6% of those treated with 2 x 50 mg. Contrary to our hypothesis, the mean initial PASI was comparable with the mean PASI mentioned in the phase II and III clinical trials. Although fatigue is not identified as a side-effect of etanercept, 10% of our patients reported fatigue as an adverse event during etanercept treatment. High BMI, indicating overweight or obesity, was found both in patients with little efficacy and in patients achieving PASI 75 or better.Use of etanercept in real practice gives impressive results, but these are generally less favourable than those published in clinical trial reports. This is probably due to the stringent conditions for reimbursement, which select for more treatment-resistant patients. Fatigue as a possible side-effect of etanercept should also be an issue for further investigation. Finally, the BMI does not seem to influence the patients' response to etanercept, although further investigations would be needed to confirm this.
Sunitinib Plus Erlotinib for the Treatment of Advanced/Metastatic Non–Small-Cell Lung Cancer: A Lead-In Study
Authors: George R. Blumenschein, Tudor Ciuleanu, Francisco Robert, Harry J.M. Groen, Tiziana Usari, Ana Ruiz-Garcia, Lesley Tye, Richard C. Chao, Erzsebet Juhasz
Journal: Journal of Thoracic Oncology (2012)
3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase and Isoprenylation Inhibitors Induce Apoptosis of Vascular Smooth Muscle Cells in Culture
Authors: Carlos Guijarro, Luis Miguel Blanco-Colio, Mónica Ortego, Covadonga Alonso, Alberto Ortiz, Juan José Plaza, Cristina Díaz, Gonzalo Hernández, Jesús Egido
Journal: Circulation Research (1998)

Abstract —Recent evidence suggests that apoptosis may be involved in the control of vascular smooth muscle cell (VSMC) number in atherosclerotic lesions. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been reported to induce apoptosis in a variety of tumor cell lines. To evaluate whether these agents also induce apoptosis of VSMCs, cultured rat VSMCs were treated with increasing doses of atorvastatin in the presence of FBS as a survival factor. The presence of apoptosis was evaluated by morphological criteria, annexin V binding, and DNA fragmentation and quantified as the proportion of hypodiploid cells by flow cytometry. Atorvastatin induced apoptosis in a dose-dependent manner, an effect also seen with simvastatin and lovastatin, but not with the hydrophilic drug pravastatin. The proapoptotic effect of statins was seen only when the inhibition of acetate incorporation into sterols was &gt;95% and was fully reversed by mevalonate, farnesyl pyrophosphate, and geranylgeranyl pyrophosphate but not by isopentenyl adenosine, ubiquinone, or squalene, suggesting a role for prenylated proteins in the regulation of VSMC apoptosis. To further assess the role of protein prenylation, VSMCs were exposed to the prenyl transferase inhibitors perillic acid and manumycin A. Both agents induced VSMC apoptosis as evaluated by the above-mentioned criteria. Finally, VSMC treatment with lipophilic statins was associated with decreased prenylation of p21-Rho B, further supporting the role of protein prenylation inhibition in statin-induced VSMC apoptosis. The present data suggest that interference with protein prenylation by HMG-CoA reductase inhibitors or other agents may provide new strategies for the prevention of neointimal thickening.