tbuckley/cabot-search huggingface dataset:
Bone mineral density and serum testosterone in chronically trained, high mileage 40–55 year old male runners
Authors: K J MacKelvie, J E Taunton, H A McKay, K M Khan
Journal: British Journal of Sports Medicine (2000)

Objectives —To identify physical activity that is beneficial for the maintenance of bone strength with increasing age by examining the relation between bone mineral density (BMD) and chronic endurance training in men. BMD at the proximal femur, its subregions, and the lumbar spine, and serum testosterone were compared between two groups of long distance runners with more than 20 years of training experience and non-athletic controls. Methods —Runners (n = 12) were divided into ( a ) high volume runners (n = 7), running 64–80 km a week, and ( b ) very high volume runners (n = 5), running more than 95 km a week, and compared with non-athletic male controls, exercising in non-endurance oriented activities two to four times a week. BMD (g/cm 2 ) at the total proximal femur, femoral neck, trochanteric region, and lumbar spine was measured by dual energy x ray absorptiometry. Total testosterone (nmol/l) and free testosterone (pmol/l) in serum were measured by radioimmunoassay from single fasting blood samples. Results —Height, weight, and age (range = 40–55 years) were not significantly different between groups. The high volume runners had significantly higher BMD at the total proximal femur (1.09 (0.17) v 0.94 (0.056)), femoral neck (0.91 (0.16) v 0.78 (0.071)), and trochanteric region (0.85 (0.14) v 0.73 (0.053)) than controls (p&lt;0.05). The differences in BMD for the proximal femur between the very high volume runners and the other two groups were not significant. There was no difference in lumbar spine BMD, total testosterone, or free testosterone between groups. However, there was a significant negative correlation between total testosterone ( r = −0.73, p&lt;0.01) and free testosterone ( r = −0.79, p&lt;0.005) and running volume in the distance runners. Conclusions —Long term distance running with training volumes less than 80 km a week had a positive effect on BMD of the proximal femur. With running volumes greater than 64 km a week, training was inversely related to testosterone levels, but levels remained within the normal range.
Target platelet antigens of autoantibodies in patients with primary biliary cirrhosis
Authors: S M Feistauer, E Penner, W R Mayr, S Panzer
Journal: Hepatology (1997)

Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver, frequently associated with thrombocytopenia. As various immune abnormalities have been described in PBC, we hypothesized that thrombocytopenia is also an autoimmune phenomenon in these patients. We therefore assessed the frequency of platelet antibodies and their target platelet glycoprotein (GP) specificities. We investigated 66 PBC patients with a median disease duration of 25 months. Twenty-two patients with alcoholic liver disease and thrombocytopenia served as controls. Specificities of platelet antibodies were determined by the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay using monoclonal antibodies directed against GPIIb/IIIa and GPIb/IX. The notion that immunoglobulins are nonspecifically bound to platelets was further evaluated by the production of eluates from antibody-coated platelets. The specificities of antibodies in these eluates were again determined by the MAIPA assay. Twenty-six PBC patients had platelet antibodies, whereas antibodies were not detectable in control alcoholic patients. Seven of 13 thrombocytopenic PBC patients had detectable antibodies. Overall, GP Ib/IX and GP IIb/IIIa served in a similar frequency as target antigens. Antibody specificities were confirmed by the production of eluates from platelets. These studies provide evidence that antibodies are specifically bound to platelets in patients with PBC and that the development of immune phenomena in PBC may also involve immuno-mediated platelet destruction.
Phase III Comparison of Two Irinotecan Dosing Regimens in Second-Line Therapy of Metastatic Colorectal Cancer
Authors: Charles S. Fuchs, Melvin R. Moore, Graydon Harker, Luis Villa, David Rinaldi, J. Randolph Hecht
Journal: Journal of Clinical Oncology (2003)

Purpose: Randomized trials in fluorouracil (FU)-refractory colorectal cancer demonstrate significant survival advantages for patients receiving irinotecan. We prospectively compared the efficacy and tolerability of two irinotecan regimens (once a week for 4 weeks followed by a 2-week rest period [weekly] v once every 3 weeks) in such patients. Patients and Methods: This multicenter, open-label, phase III study randomly assigned patients in a 1:2 ratio to irinotecan given either weekly (125 mg/m 2 ) or once every 3 weeks (350 mg/m 2 , or 300 mg/m 2 in patients who were ≥ 70 years of age, who had Eastern Cooperative Oncology Group performance status equal to 2, or who had prior pelvic irradiation). Results: With median follow-up of 15.8 months, there was no significant difference in 1-year survival (46% v 41%, respectively; P = .42), median survival (9.9 v 9.9 months, respectively; P = .43), or median time to progression (4.0 v 3.0 months, respectively; P = .54) between the two regimens. Grade 3/4 diarrhea occurred in 36% of patients treated weekly and in 19% of those treated once every 3 weeks (P = .002). Grade 3/4 neutropenia occurred in 29% of patients treated weekly and 34% of those treated once every 3 weeks (P = .35). Treatment-related mortality occurred in five patients (5.3%) receiving irinotecan weekly and three patients (1.6%) given therapy once every 3 weeks (P = .12). Global quality of life was not statistically different between treatment groups. Conclusion: Irinotecan schedules of weekly and of once every 3 weeks demonstrated similar efficacy and quality of life in patients with FU-refractory, metastatic colorectal cancer. The regimen of once every 3 weeks was associated with a significantly lower incidence of severe diarrhea.
Identification of a <i>Prg4</i>‐Expressing Articular Cartilage Progenitor Cell Population in Mice
Authors: Elena Kozhemyakina, Minjie Zhang, Andreia Ionescu, Ugur M. Ayturk, Noriaki Ono, Akio Kobayashi, Henry Kronenberg, Matthew L. Warman, Andrew B. Lassar
Journal: Arthritis & Rheumatology (2015)

Objective To generate knockin mice that express a tamoxifen‐inducible Cre recombinase from the Prg4 locus ( Prg4 GFPCreERt2 mice) and to use these animals to fate‐map the progeny of Prg4 ‐positive articular cartilage cells at various ages. Methods We crossed Prg4 GFPCreERt2 mice with Rosa26 floxlacZ or Rosa26 mTmG reporter strains, admin‐istered tamoxifen to the double heterozygous offspring at different ages, and assayed Cre‐mediated recom‐bination by histochemistry and/or fluorescence microscopy. Results In 1‐month‐old mice, the expression of the Prg4 GFPCreERt2 allele mirrored the expression of endogenous Prg4 and, when tamoxifen was admin‐istered for 10 days, caused Cre‐mediated recombination in ∼70% of the superficial‐most chondrocytes. Prg4 GFPCreERt2 ‐expressing cells were mostly confined to the top 3 cell layers of the articular cartilage in 1‐month‐old mice, but descendants of these cells were located in deeper regions of the articular cartilage in aged mice. On embryonic day 17.5, Prg4 GFPCreERt2 ‐expressing cells were largely restricted to the superficial‐most cell layer of the forming joint, yet at ∼1 year, the progeny of these cells spanned the depth of the articular cartilage. Conclusion Our results suggest that Prg4 ‐expressing cells located at the joint surface in the embryo serve as a progenitor population for all deeper layers of the mature articular cartilage. Also, our findings indicate that Prg4 GFPCreERt2 is expressed by superficial chondrocytes in young mice, but expands into deeper regions of the articular cartilage as the animals age. The Prg4 GFPCreERt2 allele should be a useful tool for inducing efficient Cre‐mediated recombination of loxP‐flanked alleles at sites of Prg4 expression.
Prostate-Specific Antigen and Pain Surrogacy Analysis in Metastatic Hormone-Refractory Prostate Cancer
Authors: Andrew J. Armstrong, Elizabeth Garrett-Mayer, Yi-Chun Ou Yang, Michael A. Carducci, Ian Tannock, Ronald de Wit, Mario Eisenberger
Journal: Journal of Clinical Oncology (2007)

It is currently unclear if early prostate-specific antigen (PSA) or pain improvements are adequate surrogates for overall survival in men with metastatic hormone-refractory prostate cancer (HRPC). Here we examined various degrees of PSA decline and pain response as surrogates for the survival benefit observed in the TAX327 trial.In the TAX327 trial, 1,006 men with HRPC were randomly assigned to receive docetaxel in two schedules, or mitoxantrone, each with prednisone: 989 men provided data on 3-month PSA decline. Surrogacy was examined for post-treatment changes in PSA and pain response using Cox proportional hazards models to calculate the proportion of treatment effect (PTE) explained by each potential surrogate.A > or = 30% PSA decline within 3 months of treatment initiation provides the highest degree of surrogacy, with a PTE of 0.66 (95% CI, 0.23 to 1.0), and was associated with a hazard ratio (HR) of 0.50 (95% CI, 0.43 to 0.58) for overall survival after adjusting for treatment effect. Introduction of a > or = 30% PSA decline is predictive of survival regardless of treatment arm. Other changes in PSA or PSA kinetics, PSA normalization, and pain responses were highly prognostic but weaker surrogates for survival.In the TAX327 trial, a PSA decline of > or = 30% within 3 months of chemotherapy initiation had the highest degree of surrogacy for overall survival, confirming data from the Southwest Oncology Group 9916 trial. However, given the wide CIs around the estimate of this moderate surrogate effect, overall survival should remain the preferred end point for phase III trials of cytotoxic agents in HRPC.
Group selection or categorical perception?
Authors: Craig T. Palmer, B. Eric Fredrickson, Christopher F. Tilley
Journal: Behavioral and Brain Sciences (1996)

Abstract Humans appear to be possible candidates for group selection because they are often said to live in bands, clans, and tribes. These terms, however, are only names for conceptual categories of people. They do not designate enduring bounded gatherings of people that might be “vehicles of selection.” Hence, group selection has probably not been a major force in human evolution.
A replication study confirms the association of <i>TNFSF4 (OX40L)</i> polymorphisms with systemic sclerosis in a large European cohort
Authors: Lara Bossini-Castillo, Jasper C A Broen, Carmen P Simeon, Lorenzo Beretta, Madelon C Vonk, Norberto Ortego-Centeno, Gerard Espinosa, Patricia Carreira, María Teresa Camps, Nuria Navarrete, María F González-Escribano, Esther Vicente-Rabaneda, Luis Rodríguez, Carlos Tolosa, José A Román-Ivorra, Inmaculada Gómez-Gracia, Francisco J García-Hernández, Iván Castellví, María Gallego, Antonio Fernández-Nebro, Rosa García-Portales, María Victoria Egurbide, Vicente Fonollosa, Paloma García de la Peña, Ana Pros, Miguel A González-Gay, Roger Hesselstrand, Gabriela Riemekasten, Torsten Witte, Marieke J H Coenen, Bobby P Koeleman, Frederic Houssiau, Vanessa Smith, Filip de Keyser, Rene Westhovens, Ellen De Langhe, Alexandre E Voskuyl, Annemie J Schuerwegh, Meng May Chee, Rajan Madhok, Paul Shiels, Carmen Fonseca, Christopher Denton, Kathleen Claes, Leonid Padykov, Annika Nordin, Øyvind Palm, Benedicte A Lie, Paolo Airó, Raffaella Scorza, Jacob M van Laar, Nicolas Hunzelmann, Alexander Kreuter, Ariane Herrick, Jane Worthington, Timothy R D J Radstake, Javier Martín, Blanca Rueda
Journal: Annals of the Rheumatic Diseases (2010)

Objectives The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features. Methods A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers. Results A pooled analysis revealed the association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI 1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant association of the four tested variants with patients with limited cutaneous SSc (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91, 95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR 1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904 minor alleles with patients positive for anti-centromere antibodies (ACA) remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25; OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR 0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to 0.97, respectively) and revealed a new risk haplotype associated with the same groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively). Conclusions The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.
Liver Disease in Children
Authors: Aymin Delgado-Borrego
Journal: JAMA (2008)

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The Relationship Between β-Cell Function and Glycated Hemoglobin
Authors: Mustafa Kanat, Diedre Winnier, Luke Norton, Nazik Arar, Chris Jenkinson, Ralph A. DeFronzo, Muhammad A. Abdul-Ghani
Journal: Diabetes Care (2011)

The study objective was to assess the relationship between β-cell function and HbA(1c).A total of 522 Mexican American subjects participated in this study. Each subject received a 75-g oral glucose tolerance test (OGTT) after a 10- to 12-h overnight fast. Insulin sensitivity was assessed with the Matsuda index. Insulin secretory rate was quantitated from deconvolution of the plasma C-peptide concentration. β-Cell function was assessed with the insulin secretion/insulin resistance (IS/IR) (disposition) index and was related to the level of HbA(1c).At HbA(1c) levels <5.5%, both the Matsuda index of insulin sensitivity and IS/IR index were constant. However, as the HbA(1c) increased >5.5%, there was a precipitous decrease in both the Matsuda index and the IS/IR index. Subjects with HbA(1c) = 6.0-6.4% had a 44 and 74% decrease in the Matsuda index and the IS/IR index, respectively, compared with subjects with HbA(1c) <5.5% (P < 0.01 for both indices). Subjects with normal glucose tolerance and HbA(1c) <5.7% had β-cell function comparable to that of subjects with normal glucose tolerance with HbA(1c) = 5.7-6.4%. However, subjects with impaired fasting glucose or impaired glucose tolerance had a marked decrease in β-cell function independent of their HbA(1c) level.The results of the current study demonstrate that in Mexican Americans, as HbA(1c) increases >6.0%, both insulin sensitivity and β-cell function decrease markedly. Performing an OGTT is pivotal for accurate identification of subjects with impaired β-cell function.
Osteoarthrosis of the hip in women and its relation to physical load at work and in the home
Authors: E. Vingard, L. Alfredsson, H. Malchau
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVES</h3> The aim of this case referent study was to investigate the relation between physical workload and osteoarthrosis of the hip in women. <h3>METHODS</h3> The study base comprised all women of ages 50-70 years, living in five counties and four towns in Sweden 1991-1994. Cases (n=230), who had undergone total hip replacement for primary osteoarthrosis of the hip were identified by means of the Swedish National Register of Total Hip Replacements, and the referents (n=273) were women without hip problems randomly selected from the study base. All women were interviewed about state of health, smoking habits, occupational history, work in the home, sports activities, etc. Each subject's history of occupational work and work in the home up to the age of 50 was divided into periods within each of which the work tasks were similar, and a questionnaire for each such period was filled in by the participants. On the basis of information given by the referents, the women were classified as having had low, medium, and high exposure to different factors. Relative risks (RRs) and 95% confidence intervals (CI) were calculated. <h3>RESULTS</h3> Physically demanding tasks at work and in the home were associated with increased RRs of osteoarthrosis of the hip in those with high exposure compared with the low exposure group. A RR in the range of 2 or higher was found for those who frequently jumped or moved between different levels (RR=2.1, CI 1.9, 4.2), who frequently climbed stairs (RR=2.1, CI 1.2, 3.6), and who had physically demanding tasks outside occupational life (RR=2.3, CI 1.5, 3.6). The highest RR (RR=4.3, CI 1.7, 11.0) was found for those exposed to high physical loads both at work and during sports activities. <h3>CONCLUSION</h3> High physical loads at work and in the home up to the age of 50 seem to be risk factors for development of severe osteoarthrosis of the hip in women.
Celecoxib and Curcumin Synergistically Inhibit the Growth of Colorectal Cancer Cells
Authors: Shahar Lev-Ari, Ludmila Strier, Diana Kazanov, Liora Madar-Shapiro, Hadas Dvory-Sobol, Ilya Pinchuk, Brigitte Marian, Dov Lichtenberg, Nadir Arber
Journal: Clinical Cancer Research (2005)

Multiple studies have indicated that cyclooxygenase-2 (COX-2) inhibitors may prevent colon cancer, which is one of the leading causes of cancer death in the western world. Recent studies, however, showed that their long-term use may be limited due to cardiovascular toxicity. This study aims to investigate whether curcumin potentiates the growth inhibitory effect of celecoxib, a specific COX-2 inhibitor, in human colon cancer cells.HT-29 and IEC-18-K-ras (expressing high levels of COX-2), Caco-2 (expressing low level of COX-2), and SW-480 (no expression of COX-2) cell lines were exposed to different concentrations of celecoxib (0-50 micromol/L), curcumin (0-20 micromol/L), and their combination. COX-2 activity was assessed by measuring prostaglandin E(2) production by enzyme-linked immunoassay. COX-2 mRNA levels were assessed by reverse transcription-PCR.Exposure to curcumin (10-15 micromol/L) and physiologic doses of celecoxib (5 micromol/L) resulted in a synergistic inhibitory effect on cell growth. Growth inhibition was associated with inhibition of proliferation and induction of apoptosis. Curcumin augmented celecoxib inhibition of prostaglandin E(2) synthesis. The drugs synergistically down-regulated COX-2 mRNA expression. Western blot analysis showed that the level of COX-1 was not altered by treatment with celecoxib, curcumin, or their combination.Curcumin potentiates the growth inhibitory effect of celecoxib by shifting the dose-response curve to the left. The synergistic growth inhibitory effect was mediated through a mechanism that probably involves inhibition of the COX-2 pathway and may involve other non-COX-2 pathways. This synergistic effect is clinically important because it can be achieved in the serum of patients receiving standard anti-inflammatory or antineoplastic dosages of celecoxib.
Cystic fibrosis transmembrane conductance regulator (CFTR) gene defects in patients with primary sclerosing cholangitis
Authors: Emmanuelle Girodon, Damien Sternberg, Olivier Chazouillères, Cécile Cazeneuve, Danielle Huot, Yvon Calmus, Raoul Poupon, Michel Goossens, Chantal Housset
Journal: Journal of Hepatology (2002)
Population based endoscopic screening for colorectal cancer
Authors: W S Atkin
Journal: Gut (2003)

We propose that there should be a national colorectal cancer screening programme in the UK, and that there is a good case to base it on a single flexible sigmoidoscopy (FS) at approximately 60 years of age, possibly supplemented by faecal occult blood testing (FOBT) after age 60 years, predominantly for the detection of early proximal cancers.

There is no longer doubt that screening is an effective method of reducing colorectal cancer (CRC) incidence and mortality rates. The US Preventive Services Task Force1 recently reviewed the evidence and gave a grade A recommendation that all men and women over the age of 50 years should be screened for CRC. In the UK, the Department of Health has demonstrated its commitment to CRC screening by funding a national demonstration pilot to assess the feasibility and acceptability of FOBT in the general population.2 Together with the MRC it is also funding a randomised trial of a single FS screen offered at around age 60 years with colonoscopy for those found at FS to have high risk adenomas. The trial recently reported3 that FS is acceptable, feasible, and safe but has yet to report on the magnitude and duration of efficacy. The FOBT pilot was completed in mid-2002 and results are due to be presented to ministers in early 2003. Colonoscopy is not considered a feasible option for mass screening in the UK because of the personal commitment required of the screenee, the risks of perforation, and manpower issues.

The FOBT regimen under consideration in …