tbuckley/cabot-search huggingface dataset:
The Association of Rate of Weight Gain During Early Adulthood With the Prevalence of Subclinical Coronary Artery Disease in Recently Diagnosed Type 2 Diabetes: The MAXWEL-CAD Study
Authors: Soo Lim, Sung Hee Choi, Kyoung Min Kim, Sang Il Choi, Eun Ju Chun, Min Joo Kim, Kyong Soo Park, Hak Chul Jang, Naveed Sattar
Journal: Diabetes Care (2014)

OBJECTIVE To investigate the association of the rate of weight gain (Ratemax_wt) between the age of 20 years and the age of maximum lifetime weight gain with indicators of subclinical coronary artery disease (CAD) at the time of diagnosis of type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS We studied 1,724 consecutive Korean subjects aged ≥30 years with recently diagnosed (within 3 months) T2D and one or more cardiovascular risk factors to investigate the association of Ratemax_wt with subclinical CAD. We used 64-slice cardiac computed tomography angiography to evaluate the degree of coronary artery stenosis, multivessel involvement, plaque characteristics, and coronary artery calcium score (CACS). Body weight at age 20 years (Wt20y) was obtained from participant records. Participants recalled their maximum weight (Wtmax) before T2D diagnosis and age at maximum weight (Agemax_wt). The Ratemax_wt was calculated as (Wtmax – Wt20y) / (Agemax_wt – 20 years). RESULTS The prevalence of coronary artery stenosis (≥50%), multivessel involvement (two or more vessels), plaque characteristics, and CACS ≥100 were 11.4%, 6.6%, 19.7%, and 12.8%, respectively. Mean Wt20y and Wtmax were 60.1 ± 10.5 and 73.0 ± 11.5 kg, respectively. Mean Agemax_wt was 41.3 ± 10.7 years, and Ratemax_wt was 0.59 ± 0.56 kg/year. After adjusting for cardiovascular risk factors, including current BMI, the highest quarter of prior weight gain was significantly associated with coronary artery stenosis, multivessel involvement, and plaque characteristics, particularly mixed and noncalcified plaque. CONCLUSIONS The findings suggest that a greater rate of prior weight gain may accelerate the development of subclinical vascular complications in patients with newly diagnosed T2D.
Lymphovascular Invasion Is Independently Associated With Overall Survival, Cause-Specific Survival, and Local and Distant Recurrence in Patients With Negative Lymph Nodes at Radical Cystectomy
Authors: Yair Lotan, Amit Gupta, Shahrokh F. Shariat, Ganesh S. Palapattu, Amnon Vazina, Pierre I. Karakiewicz, Patrick J. Bastian, Craig G. Rogers, Gilad Amiel, Paul Perotte, Mark P. Schoenberg, Seth P. Lerner, Arthur I. Sagalowsky
Journal: Journal of Clinical Oncology (2005)

Purpose We hypothesized that bladder cancer patients with associated lymphovascular invasion (LVI) are at increased risk of occult metastases. Methods A multi-institutional group (University of Texas Southwestern [Dallas, TX], Baylor College of Medicine [Houston, TX], Johns Hopkins University [Baltimore, MD]) carried out a retrospective study of 958 patients who underwent cystectomy for bladder cancer between 1984 and 2003. Of patients with transitional-cell carcinoma (n = 776), LVI status was available for 750. LVI was defined as the presence of tumor cells within an endothelium-lined space. Results LVI was present in 36.4% (273 of 750) overall, involving 26% (151 of 581) and 72% (122 of 169) of node-negative and node-positive patients, respectively. Prevalence of LVI increased with higher pathologic stage (9.0%, 23%, 60%, and 78%, for T1, T2, T3, and T4, respectively; P &lt; .001). Using multivariate Cox regression analyses including age, stage, grade, and number of pelvic lymph nodes removed, LVI was an independent predictor of local (HR = 2.03, P = .049), distant (HR = 2.60, P = .0011), and overall (HR = 2.02, P = .0003) recurrence in node-negative patients. LVI was an independent predictor of overall (HR = 1.84, P = .0002) and cause-specific (HR = 2.07, P = .0012) survival in node-negative patients. LVI maintained its independent predictor status in competing risks regression models (P = .013), where other-cause mortality was considered as a competing risk. LVI was not a predictor of recurrence or survival in node-positive patients. Conclusion LVI is an independent predictor of recurrence and decreased cause-specific and overall survival in patients who undergo cystectomy for invasive bladder cancer and are node-negative. These patients represent a high risk group that may benefit from integrated therapy with cystectomy and perioperative systemic chemotherapy.
Biomarkers and Mechanistic Approaches in Environmental Epidemiology
Authors: Jonathan M. Links, Thomas W. Kensler, John D. Groopman
Journal: Annual Review of Public Health (1995)

Environmental epidemiological research involves the identification of relationships between previous exposures to putative causative agents and subsequent biological effects with study populations. Such relationships are often hard to fully characterize because of difficulties in accurately quantifying exposure, dose, and effect. Biomarkers are indicators, residing in biological systems or samples, of exposure, dose, effect, or susceptibility. Biomarkers of exposure indicate the presence of previous exposure to an environmental agent; a biomarker of dose bears a quantitative relationship to previous exposure or dose; these include exogenous substances, interactive products, or interactions that change the status of the target molecule. Biomarkers of effect indicate the presence and magnitude of a biological response to exposure to an environmental agent; these include endogenous components, or measures of the functional capacity or state of the system. Biomarkers of susceptibility indicate an elevated sensitivity to the effects of an environmental agent; these include the presence or absence of an endogenous component, or abnormal functional responses to an administered challenge. The development of molecular biomarkers for environmental agents is based upon specific knowledge of metabolism, interactive product formation, and general mechanisms of action. The validation of any biomarker-effect link requires parallel experimental animal and human epidemiological studies.
Use of influenza and pneumococcal vaccines in people with diabetes.
Authors: S A Smith, G A Poland
Journal: Diabetes Care (2000)

p roviders are not convinced of the threat of c e rtain infectious illnesses or the likelihood of benefit from vaccination. Altern a t i v e l y, immunization of individuals with diabetes may be one of the many clinical pro c e s s e s of care that has been shown to be deficient for this group of patients (7‐10). Initially for practical reasons and later for ethical reasons, there have been few p l a c e b o - c o n t rolled studies designed to demonstrate the efficacy of influenza and pneumococcal immunization specifically in individuals with diabetes. In addition, there a re few clinical studies that have examined the benefit of glycemic control, antibiotics, antiviral agents, and other nonvaccine meas u res in preventing and controlling infection. Current vaccine recommendations for people with diabetes are based on historical o b s e rvations in studies from population g roups that have included only a minority of patients with diabetes. What is the evidence that people with diabetes benefit f rom these immunizations? For the purpose of this re v i e w, we will examine the impact of two vaccine-preventable illnesses: influenza and pneumococcal infection. We will first examine the evidence re g a rding the immune re s p o n s e to viral and bacterial illness in people with diabetes. We will also review the evidence for the risks of infection in diabetes as it relates to antibody response, cell-mediated i m m u n i t y, leukocyte function, colonization rates, epidemiologic evidence for infection, immune response to immunization, and e fficacy of vaccination. We will then systematically review the clinical re p o rts of infection, vaccine immunogenicity, and vaccine effectiveness for influenza and pneumococcus in people with diabetes. F i n a l l y, we will review general vaccine implementation strategies. Because most studies re p o rting patient c o h o rts and outcomes give limited and variable information about patients with diabetes, we felt that combining re s e a rch re s u l t s (a meta-analysis) would not be valid. In addition to our concerns about this heterog e n e i t y, confounders such as age and underlying card i o p u l m o n a ry disease make risk assessment of diabetes by itself diff i c u l t . T h e re f o re, we have elected to provide a narrative re v i e w. Primary articles were identified f rom a Medline literature search without time restriction, using the key words immunization, vaccination, influenza, pneumococcus, and diabetes. Additional sourc e s w e re then identified from the re f e re n c e s listed from these primary sources. Searc h e s w e re perf o rmed using the last 2 years of C u rrent Contents. Further information was also obtained from contacts with the prim a ry authors of published art i c l e s .
Three Ia species with different structures and alloantigenic determinants in an HLA-homozygous cell line.
Authors: N Tanigaki, R Tosi, R J Duquesnoy, G B Ferrara
Journal: The Journal of Experimental Medicine (1983)

Three distinct molecular subsets with different structures and alloantigenic determinants were identified in human Ia antigens from cells of an HLA-Dw7 homozygous cell line. The subsets carried DR7 specificity, BR4X7 supertypic specificity and MB2 supertypic specificity, respectively, and were immunospecifically separated by the use of operationally monospecific alloantisera. These specificities showed HLA-linked segregation in families and they were distributed in the population according to different but partially overlapping patterns. On peptide mapping analysis, the three subsets showed marked differences in the beta-chains. The alpha-chains of DR7 and BR4X7 subsets were very similar to each other, whereas the alpha-chains of MB2 subset were distinctive from those of DR7 and BR4X7. These data indicate the presence of a minimum of three HLA-linked loci; DR locus, a locus that encodes BR4X7, and a locus that encodes MB2, and substantiate the three-loci concept for the genetic control of human I antigens.
1,25-Dihydroxyvitamin D <sub>3</sub> Increases In Vitro Vascular Calcification by Modulating Secretion of Endogenous Parathyroid Hormone–Related Peptide
Authors: Shuichi Jono, Yoshiki Nishizawa, Atsushi Shioi, Hirotoshi Morii
Journal: Circulation (1998)

A significant association between vascular calcification and osteoporosis has been noted, suggesting that calcium homeostasis is important in vascular calcification as well as in osteoporosis. Moreover, results of our previous studies suggest that calcium-regulating hormones such as parathyroid hormone-related peptide (PTHrP) may modulate vascular calcification. Therefore, we hypothesized that 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] may have a direct impact on the calcium-regulating system of vascular smooth muscle cells, resulting in deposition of calcium in vascular wall.We investigated the effect of 1,25(OH)2D3 on in vitro calcification by bovine vascular smooth muscle cells (BVSMCs). 1,25(OH)2D3 dose dependently increased BVSMC calcification and alkaline phosphatase activity. 1,25(OH)2D3 also decreased secretion of PTHrP by BVSMCs in a dose-dependent manner and depressed its gene expression. Furthermore, exogenous PTHrP (fragment 1-34) antagonized the stimulatory effect of 1,25(OH)2D3 on BVSMCs. Finally, 1,25(OH)2D3 dose dependently increased the expression of the osteopontin gene, one of the bone matrix proteins in BVSMCs, contributing to its stimulatory action on BVSMC calcification.These data suggest that 1,25(OH)2D3 exerts a stimulatory effect on vascular calcification through direct inhibition of the expression of PTHrP in BVSMCs as an endogenous inhibitor of vascular calcification. Moreover, the stimulatory effects of 1,25(OH)2D3 on alkaline phosphatase activity and osteopontin expression may contribute to its promoting action in vascular calcification.
Oxygen Consumption of Normal and Atherosclerotic Intima
Authors: ARTHUR F. WHEREAT
Journal: Circulation Research (1961)

This investigation has been a comparison of the intimal metabolism of the aorta in normal and atherosclerotic rabbits, and at various aortic locations. The thinnest possible layer of tissue was separated from the inner surface of the aorta. This layer proved to be intima with a small and fairly constant amount of media (smooth muscle). The intima from the animals rendered atherosclerotic by cholesterol-feeding showed a much higher rate of oxygen consumption than the controls when succinate was used as a substrate. Moreover, the most atherosclerotic area (the aortic arch) showed a higher oxygen consumption than the less atherosclerotic areas (the thoracic and abdominal areas). This acceleration of oxygen consumption is presumably due to either an increased energy requirement (for either accelerated synthesis or catabolism) or an uncoupling of oxidative phosphorylation.
Depolarization and cAMP Elevation Rapidly Recruit TrkB to the Plasma Membrane of CNS Neurons
Authors: Anke Meyer-Franke, George A Wilkinson, Alex Kruttgen, Minjie Hu, Elizabeth Munro, Martin G Hanson, Louis F Reichardt, Ben A Barres
Journal: Neuron (1998)

Here, we describe a novel mechanism for the rapid regulation of surface levels of the neurotrophin receptor TrkB. Unlike nodose ganglion neurons, both retinal ganglion cells (RGCs) and spinal motor neurons (SMNs) in culture display only low levels of surface TrkB, though high levels are present intracellularly. Within minutes of depolarization or cAMP elevation, surface TrkB levels increase by nearly 4-fold, and this increase is not blocked by cycloheximide. These findings suggest that activity and cAMP elevation rapidly recruit TrkB to the plasma membrane by translocation from intracellular stores. We propose that a fundamental difference between peripheral nervous system (PNS) and central nervous system (CNS) neurons is the activity dependence of CNS neurons for responsiveness to their peptide trophic factors and that differences in membrane compartmentalization of the receptors underlie this difference.
Lifetime Recreational Exercise Activity and Breast Cancer Risk Among Black Women and White Women
Authors: Leslie Bernstein, Alpa V. Patel, Giske Ursin, Jane Sullivan-Halley, Michael F. Press, Dennis Deapen, Jesse A. Berlin, Janet R. Daling, Jill A. McDonald, Sandra A. Norman, Kathleen E. Malone, Brian L. Strom, Jonathan Liff, Suzanne G. Folger, Michael S. Simon, Ronald T. Burkman, Polly A. Marchbanks, Linda K. Weiss, Robert Spirtas
Journal: JNCI Journal of the National Cancer Institute (2005)

Physical inactivity is a potentially modifiable breast cancer risk factor. Because few data on this relationship exist for black women, we examined the relationship between breast cancer risk and lifetime and time- or age-specific measures of recreational exercise activity among white women and among black women.The Women's Contraceptive and Reproductive Experiences Study was a multicenter population-based case-control study of black women and white women aged 35-64 years with newly diagnosed invasive breast cancer. We collected detailed histories of lifetime recreational exercise activity during in-person interviews with 4538 case patients with breast cancer (1605 black and 2933 white) and 4649 control subjects (1646 black and 3033 white). Control subjects were frequency-matched to case patients on age, race, and study site. We examined associations between exercise activity measures (metabolic equivalents of energy expenditure [MET]-hours per week per year) and breast cancer risk overall and among subgroups defined by race, other breast cancer risk factors, and tumor characteristics by use of unconditional logistic regression. All statistical tests were two-sided.Among all women, decreased breast cancer risk was associated with increased levels of lifetime exercise activity (e.g., average MET-hours per week per year, P(trend) = .002). An average annual lifetime exercise activity that was greater than the median level for active control subjects was associated with an approximately 20% lower risk of breast cancer, compared with that for inactivity (for 6.7-15.1 MET-hours/week/year, odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.71 to 0.93; for > or =15.2 MET-hours/week/year, OR = 0.80, 95% CI = 0.70 to 0.92). The inverse associations did not differ between black and white women (for MET-hours/week/year, P(trend) = .003 and P(trend) = .09, respectively; homogeneity of trends P = .16). No modification of risk was observed by disease stage, estrogen receptor status, or any breast cancer risk factor other than first-degree family history of breast cancer.This study supports an inverse association between physical activity and breast cancer among black women and among white women.
Supplementation With Conjugated Linoleic Acid Causes Isomer-Dependent Oxidative Stress and Elevated C-Reactive Protein
Authors: Ulf Risérus, Samar Basu, Stefan Jovinge, Gunilla Nordin Fredrikson, Johan Ärnlöv, Bengt Vessby
Journal: Circulation (2002)

Conjugated linoleic acids (CLAs), a group of fatty acids shown to have beneficial effects in animals, are also used as weight loss supplements. Recently, we reported that the t10c12 CLA-isomer caused insulin resistance in abdominally obese men via unknown mechanisms. The aim of the present study was to examine whether CLA has isomer-specific effects on oxidative stress or inflammatory biomarkers and to investigate the relationship between these factors and induced insulin resistance.In a double-blind placebo-controlled trial, 60 men with metabolic syndrome were randomized to one of 3 groups receiving t10c12 CLA, a CLA mixture, or placebo for 12 weeks. Insulin sensitivity (euglycemic clamp), serum lipids, in vivo lipid peroxidation (determined as urinary 8-iso-PGF(2alpha) [F2-isoprostanes]), 15-ketodihydro PGF(2alpha), plasma vitamin E, plasma C-reactive protein, tumor necrosis factor-alpha, and interleukin-6 were assessed before and after treatment. Supplementation with t10c12 CLA markedly increased 8-iso-PGF(2alpha) (578%) and C-reactive protein (110%) compared with placebo (P<0.0001 and P<0.01, respectively) and independent of changes in hyperglycemia or dyslipidemia. The increases in 8-iso-PGF(2alpha), but not in C-reactive protein, were significantly and independently related to aggravated insulin resistance. Oxidative stress was related to increased vitamin E levels, suggesting a compensatory mechanism.t10c12 CLA supplementation increases oxidative stress and inflammatory biomarkers in obese men. The oxidative stress seems closely related to induced insulin resistance, suggesting a link between the fatty acid-induced lipid peroxidation seen in the present study and insulin resistance. These unfavorable effects of t10c12 CLA might be of clinical importance with regard to cardiovascular disease, in consideration of the widespread use of dietary supplements containing this fatty acid.
Comment on: Richter et al. Serum Levels of the Adipokine Progranulin Depend on Renal Function. Diabetes Care 2013;36:410–414
Authors: Jakob Triebel
Journal: Diabetes Care (2013)

Richter et al. (1) report an association between serum levels of the adipokine progranulin and chronic kidney disease (CKD) and demonstrate higher progranulin levels with deteriorating renal function—the highest progranulin levels being observed in stage 5 of CKD. The authors conclude that impaired renal clearance might account …
Prevalence and types of androgenetic alopecia in Shanghai, China: a community-based study
Authors: F. Xu, Y-Y. Sheng, Z-L. Mu, W. Lou, J. Zhou, Y-T. Ren, S-S. Qi, X-S. Wang, Z-W. Fu, Q-P. Yang
Journal: British Journal of Dermatology (2009)

There are ethnic differences in the prevalence and types of androgenetic alopecia (AGA). Although there have been several reports on the prevalence and types of AGA in caucasian and Asian populations, there are very few data on a Chinese population that have been derived from a sufficient number of samples.To estimate the prevalence and types of AGA in a Chinese population, and to compare the results with those in caucasians and Koreans reported previously in the literature.A population-based cross-sectional study was carried out in 7056 subjects (3519 men and 3537 women) from May 2006 to December 2006 in a community of Shanghai. Questionnaires were completed during face-to-face interviews at the subjects' homes. The degree of AGA was classified according to the Norwood and Ludwig classifications.The prevalence of AGA in Chinese men was 19.9%, and the prevalence of female pattern AGA in men was 0.1%. The most common type in men was type III vertex (3.5%). The prevalence of AGA in women was 3.1%, while male pattern AGA was found in those aged over 50 years (0.4%), and the most common type was type I (Ludwig classification) (1.4%). A family history of AGA was present in 55.8% of men and 32.4% of women with AGA.The prevalence of AGA in Chinese men was lower than in caucasian men but was similar to that in Korean men; however, over the age of 60 years it was approaching that in caucasian men but was higher than that in Korean men. The most common type in Chinese men with AGA was type III vertex. Interestingly, the prevalence of AGA in Chinese women was lower than that in Korean women and caucasian women, and type I was the most common type (Ludwig classification).
Prolonged immunostimulatory effect of low-dose polyethylene glycol interleukin 2 in patients with human immunodeficiency virus type 1 infection.
Authors: H Teppler, G Kaplan, K A Smith, A L Montana, P Meyn, Z A Cohn
Journal: The Journal of Experimental Medicine (1993)

13 patients with human immunodeficiency virus type 1 infection class II-IV, but without opportunistic infection or neoplasm, received 6 micrograms (3.6 x 10(4) IU) of polyethylene glycol recombinant human interleukin 2 (PEG IL-2) intradermally twice a week for 4 mo were then followed for an additional 6 mo. Clinical, immunological, and viral parameters were monitored in the patients, all of whom were taking zidovudine. The cutaneous administration of PEG IL-2 resulted in an indurated zone resembling a delayed-type hypersensitivity response of 26 +/- 1 mm diameter (676 mm2) at 72-96 h after injection throughout the 4 mo of administration. This dose, which was appreciably lower than in most previous trials, was not associated with local or systemic toxicity. No increase in the viral burden of circulating leukocytes or plasma occurred. A number of immunological functions were stimulated by this course of therapy. All patients demonstrated high levels of lymphokine-activated killer cell activity by cells freshly removed from the circulation and in the absence of in vitro exposure to IL-2. Natural killer cell activity was also enhanced. Limiting dilution analysis revealed an increase in the frequency of IL-2-responsive cells from abnormally low to levels above normal during the course of injections. In a subgroup of four patients with &amp;gt; or = 400 CD4+ T cells/microliter at entry, there was a trend to sustained increases in CD4+ T cell numbers. However, this increase did not reach statistical significance. This subset of patients also exhibited higher proliferative responses to phytohemagglutinin as mitogen. Several of these effects persisted for 3-6 mo after cessation of therapy. In conclusion, low-dose IL-2 regimens lead to sustained immune enhancement in the absence of toxicity. We suggest pursuit of this approach for further clinical trials both as prophylaxis and therapy.