tbuckley/cabot-search huggingface dataset:
Immune thrombocytopenic purpura in Hodgkin disease
Authors: Kamran Hassidim, Robert McMillan, Michael S. Conjalka, John Morrison
Journal: American Journal of Hematology (1979)

Abstract Immune thrombocytopenic purpura is rarely seen in Hodgkin disease and the presence of platelet‐associated antibody has not been previously reported in these patients. A patient with Hodgkin disease is described who developed a destructive thrombocytopenia demonstrated by shortened platelet survival. In conjunction with his thrombocytopenia, he had marked elevation of platelet‐associated immunoglobulin G levels (nanograms IgG per 10 9 platelets: 15,187 prior to splenectomy and 71,130 and 81,900 after surgery). Mean values (± SD) of control subjects averaged 1,975 ± 381 and four patients with Hodgkin disease and normal platelet counts had levels ranging from 1,581 to 4,011. We suggest that this patient had immune‐mediated thrombocytopenia; whether the increase in platelet‐associated immunoglobulin G was due to antiplatelet antibody or to adsorbed or phagocytosed immune complexes cannot be demonstrated by these studies. The platelet‐associated immunoglobulin G test may be useful in evaluating these patients.
G Protein–Coupled Receptor Oligomerization
Authors: Gerda E. Breitwieser
Journal: Circulation Research (2004)

The cardiovascular system is richly endowed with G protein–coupled receptors (GPCRs), members of the largest family of plasma membrane-localized receptors. During the last 10 years, it has become increasingly clear that many, if not all, GPCRs function in oligomeric complexes, as either homo- or hetero-oligomers. This review explores the mechanistic implications of GPCR dimerization and/or oligomerization on receptor activation and interactions with G proteins. The effects of GPCR oligomerization on receptor pharmacology, GPCR-mediated signaling, and potential contributions to GPCR crosstalk will be considered in the context of receptors important in the cardiovascular system. Our evolving understanding of the structural and functional consequences of GPCR oligomerization may provide novel and more selective sites for pharmacological tuning of cardiovascular function.
Receptors for Luteinizing Hormone Releasing Hormone Expressed on Human Renal Cell Carcinomas Can Be Used for Targeted Chemotherapy with Cytotoxic Luteinizing Hormone Releasing Hormone Analogues
Authors: Gunhild Keller, Andrew V. Schally, Timo Gaiser, Attila Nagy, Benjamin Baker, Gabor Halmos, Jörg B. Engel
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To determine the expression of luteinizing hormone releasing hormone (LHRH) receptors in specimens and cell lines of human renal cell carcinoma (RCC) and to evaluate the antitumor efficacy of targeted therapy with a cytotoxic analogue of LHRH, AN-207, in vivo. AN-207, consisting of [D-Lys6] LHRH linked to a cytotoxic radical, 2-pyrrolinodoxorubicin (AN-201), binds with high affinity to LHRH receptors and can be targeted to tumors expressing these receptors. Experimental Design: The expression of LHRH receptors was investigated in 28 surgically removed specimens of human renal cell carcinoma (RCC) by immunohistochemistry and in three human RCC cell lines A-498, ACHN, and 786-0 by radioreceptor assays, Western immunoblotting, and reverse transcription-PCR analysis. Antitumor efficacy of AN-207 was examined in experimental models of these cell lines. Results: Positive staining for LHRH receptors was found in all (28 of 28) of the examined human RCC specimens. mRNA for LHRH receptor, receptor protein, and LHRH binding sites were detected in all three cell lines. AN-207 significantly (P &amp;lt; 0.05) inhibited the growth of A-498, ACHN, and 786-0 xenografts in vivo producing a 67.8% to 73.8% decrease in tumor volume and a 62.2% to 77.3% reduction in tumor weight. Nontargeted cytotoxic radical AN-201 had no significant antitumor effects. Blockade of LHRH receptors by an excess of LHRH agonist Decapeptyl suppressed tumor inhibitory effects of AN-207. Conclusions: Our findings indicate that LHRH receptors are expressed in human RCC specimens and can be used for targeted chemotherapy with cytotoxic LHRH analogues.
Effects of a new cardioselective beta-adrenergic blocker (tolamolol) on exercise tolerance in patients with angina pectoris
Authors: N. K. Sood, C. W. H. Havard
Journal: Thorax (1973)

The effect of oral and intravenous tolamolol on exercise tolerance was assessed in 11 patients with angina pectoris. Patients were selected on the basis of an absence of placebo response and the reliable reproducibility of anginal pain and electrocardiographic changes with exercise on a constant load Schönander-Elema bicycle ergometer. The effect of tolamolol on exercise time and heart rate was compared with that of propranolol. Tolamolol was shown to increase exercise tolerance and the effect was comparable to that of propranolol. Tolamolol did not produce a significant increase in airways resistance nor were any untoward side effects noted.
Outdoor swimming pools and the risks of asthma and allergies during adolescence
Authors: A. Bernard, M. Nickmilder, C. Voisin
Journal: European Respiratory Journal (2008)

Exposure to indoor chlorinated swimming pools can be detrimental to the airways of swimmers and increase asthma risks but it is unknown whether these effects concern outdoor pools. The present study examined 847 secondary school adolescents who had attended residential or nonresidential outdoor chlorinated pools at a variable rate. The main outcomes were: ever asthma (physician-diagnosed at any time); current asthma (ever asthma under medication and/or with exercise-induced bronchoconstriction); elevated exhaled nitric oxide; and aeroallergen-specific immunoglobulin (Ig)E in serum. The prevalence of ever and current asthma significantly increased with the lifetime number of hours spent in outdoor pools by up to four and eight times, respectively, among adolescents with the highest attendance (>500 h) and a low exposure to indoor pools (<250 h). Odds for asthma were significantly increased among adolescents with total serum IgE >25 kIU x L(-1), on average by 1-2 units for each 100-h increase in pool attendance. Use of residential outdoor pools was also associated with higher risks of elevated exhaled nitric oxide and sensitisation to cat or house dust mite allergens. Outdoor chlorinated swimming pool attendance is associated with higher risks of asthma, airways inflammation and some respiratory allergies.
Guidelines for time-to-event end point definitions in sarcomas and gastrointestinal stromal tumors (GIST) trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)
Authors: C.A. Bellera, N. Penel, M. Ouali, S. Bonvalot, P.G. Casali, O.S. Nielsen, M. Delannes, S. Litière, F. Bonnetain, T.S. Dabakuyo, R.S. Benjamin, J.-Y. Blay, B.N. Bui, F. Collin, T.F. Delaney, F. Duffaud, T. Filleron, M. Fiore, H. Gelderblom, S. George, R. Grimer, P. Grosclaude, A. Gronchi, R. Haas, P. Hohenberger, R. Issels, A. Italiano, V. Jooste, A. Krarup-Hansen, C. Le Péchoux, C. Mussi, O. Oberlin, S. Patel, S. Piperno-Neumann, C. Raut, I. Ray-Coquard, P. Rutkowski, S. Schuetze, S. Sleijfer, E. Stoeckle, M. Van Glabbeke, P. Woll, S. Gourgou-Bourgade, S. Mathoulin-Pélissier
Journal: Annals of Oncology (2014)
Superior performance in WAIS-R block design among top-level rugby players: Table 1
Authors: S Kasahara, H Mashiko, S-I Niwa
Journal: British Journal of Sports Medicine (2008)

Following a report that a well-known soccer player achieved a perfect score on the Block Design subtest of WAIS-R, WAIS-R was conducted on 31 skilled rugby players.Twenty-seven of the 31 players were recruited for further analyses.In 14 of 27 players, Block Design scores were the highest of the 11 subtests. In addition to Block Design scores that exceeded the scores for the other subtests, the players' Block Design scores were also better than scores for the standard sample.The Block Design is related to spatial cognitive ability. These results showed that highly skilled players of field and ball games possess high spatial cognitive abilities.
A clinical microchip for evaluation of single immune cells reveals high functional heterogeneity in phenotypically similar T cells
Authors: Chao Ma, Rong Fan, Habib Ahmad, Qihui Shi, Begonya Comin-Anduix, Thinle Chodon, Richard C Koya, Chao-Chao Liu, Gabriel A Kwong, Caius G Radu, Antoni Ribas, James R Heath
Journal: Nature Medicine (2011)
Response of the rat small-intestine epithelium to methotrexate.
Authors: J A Taminiau, D G Gall, J R Hamilton
Journal: Gut (1980)

ABSTRACT. Macrophages are prominent participants in crescentic glomerulonephritis (GN) and have been suggested to be the major source of TNF in this cell-mediated form of glomerular inflammation. Intrinsic renal cells also have the capacity to produce TNF. For dissecting the contribution of local <i>versus</i> bone marrow (BM)-derived TNF in inflammatory renal injury, TNF chimeric mice were created by transplanting normal wild-type (WT) BM into irradiated TNF-deficient recipients (WT→TNF<sup>−</sup><sup>/</sup><sup>−</sup> chimeras) and <i>vice versa</i> (TNF<sup>−</sup><sup>/</sup><sup>−</sup>→WT chimeras). A model of crescentic GN induced by an intravenous injection of sheep anti-murine glomerular basement membrane antibody was studied in WT mice, mice with complete TNF deficiency (TNF−/−), and chimeric mice. Crescentic GN was attenuated in TNF−/− mice with fewer crescents (crescents, 13.7 ± 1.7% of glomeruli) and reduced functional indices of renal injury (serum creatinine, 15.2 ± 0.8 μmol/L). Similar protection (crescents, 14.3 ± 1.9% of glomeruli; serum creatinine, 18.9 ± 1.1 μmol/L) was observed in chimeric mice with intact BM but absent renal-derived TNF (WT→TNF<sup>−</sup><sup>/</sup><sup>−</sup> chimeras), suggesting a minor contribution of infiltrating leukocytes to TNF-mediated renal injury. Chimeric mice with TNF-deficient leukocytes but intact intrinsic renal cell-derived TNF (crescents, 20.5 ± 2.0% of glomeruli; serum creatinine, 21.6 ± 1.4 μmol/L) developed similar crescentic GN to WT mice (crescents, 22.3 ± 1.4% of glomeruli; serum creatinine, 24.8 ± 1.9 μmol/L). Cutaneous delayed-type hypersensitivity after subdermal challenge with the nephritogenic antigen was attenuated in the absence of BM cell-derived TNF but unaffected in WT→TNF<sup>−</sup><sup>/</sup><sup>−</sup> chimeric mice. These studies suggest that intrinsic renal cells are the major cellular source of TNF contributing to inflammatory injury in crescentic GN. E-mail: peter.tipping@med.monash.edu.au
Impact of comorbidity on physical function in patients with rheumatoid arthritis
Authors: Helga Radner, Josef S Smolen, Daniel Aletaha
Journal: Annals of the Rheumatic Diseases (2009)

Background Physical disability is a main outcome in rheumatoid arthritis (RA) which tends to increase with comorbidities. However, the extent to which comorbidities contribute to the multifactorial process of disability has not been investigated. Objective To quantify the contribution of comorbidity to physical disability in patients with RA. Methods In a prospective cohort study, age-adjusted Charlson comorbidity index (CCI A ), serial measurements of disease activity and functional disability (evaluated by the Health Assessment Questionnaire Disability Index, HAQ) of 380 patients with established RA seen at an outpatient clinic over 1 year (June 2007 to July 2008) were ascertained. The association between comorbidity and physical disability was assessed using analysis of variance (ANOVA) and adjusted general linear regression models. Results Four patient groups with increasing levels of comorbidity (CCI A 0, 1–2, 3–4 and 5–9; potential range 0–38) were defined. Mean HAQ scores were significantly different across these groups (0.67, 0.80, 1.24, 1.40, respectively; p&lt;0.001) and also when adjusted for disease activity, gender and disease duration in the regression model (0.84, 0.88, 1.14, 1.48, respectively; p&lt;0.001). The effects of CCI A on disability were similar within different strata of disease activity: namely, remission (0.26, 0.31, 0.48 and 0.88, p&lt;0.01); low disease activity (0.83, 0.78, 0.98 and 1.36, p&lt;0.01); and moderate to high disease activity (1.22, 1.33, 1.70 and 1.91, p&lt;0.01), and thus were independent of disease activity. Several sensitivity analyses, including the use of the Short Form Health Survey (SF-36), confirmed these observations. Conclusion Physical disability becomes worse with increasing levels of comorbidity, irrespective of disease activity.
HLA-DRB1*0901 lowers anti-cyclic citrullinated peptide antibody levels in Japanese patients with rheumatoid arthritis
Authors: Y. Okada, A. Suzuki, R. Yamada, Y. Kochi, K. Shimane, K. Myouzen, M. Kubo, Y. Nakamura, K. Yamamoto
Journal: Annals of the Rheumatic Diseases (2009)

Anti-cyclic citrullinated peptide (anti-CCP) antibody is a highly specific biomarker for rheumatoid arthritis (RA), and is recognised as a predictor of the development of RA.1 2 It has been demonstrated that some HLA-DRB1 alleles, such as shared epitope (SE) alleles, significantly contribute to the positivity of anti-CCP antibody and the susceptibility of anti-CCP antibody-positive RA.3 4 However, the quantitative effect of HLA-DRB1 alleles on anti-CCP antibody levels in RA patients is controversial.3 5 6 Therefore, we carried out a large-scale study to study the quantitative effects of HLA-DRB1 alleles on anti-CCP antibody levels in Japanese patients with RA.

A total of 2384 Japanese patients with RA was recruited through several medical institutes of Japan under the support of the BioBank Japan Project7 (age 61.5±11.8 years (mean±SD), 81.2% were women). All patients fulfilled the American College of Rheumatology revised criteria for RA, and provided written informed consent. Serum anti-CCP antibody levels were assayed using the second-generation anti-CCP ELISA kit (DIASTAT Anti-CCP; MBL, Nagoya, Japan) with …
AN EXPERIMENTAL STUDY OF BONE AND JOINT TUBERCULOSIS
Authors: John Fraser
Journal: The Journal of Experimental Medicine (1913)

While one can not assert that the conclusions which experiments appear to offer must of necessity correspond to the conditions which arise clinically in man, nevertheless these results, if definite, must tend to show the direction in which the truth lies. The conclusions which may be drawn from this research are as follows: 1. Direct infection of the medulla of a long bone is unlikely to lead to the development of a tuberculous osteomyelitis. 2. Inoculation of the interior of a joint with tubercle bacilli readily produces tubercle of the synovial membrane. 3. From such an infected joint the epiphysis or metaphysis of the bone becomes diseased. 4. Infection of the arterial heart blood does not result in the local development of tubercle of the bones or joints. 5. Infection of the main artery supplying a limb leads to the development of tuberculous disease of certain of the joints of that limb. 6. Direct infection of the nutrient artery does not result in tuberculous osteomyelitis of the bone.
Kidney Function and Risk of Peripheral Arterial Disease
Authors: Keattiyoat Wattanakit, Aaron R. Folsom, Elizabeth Selvin, Josef Coresh, Alan T. Hirsch, Beth D. Weatherley
Journal: Journal of the American Society of Nephrology (2007)

Chronic kidney disease (CKD) is associated with an increased risk for cardiovascular disease, but its association with peripheral arterial disease (PAD) is unclear. With the use of data from the Atherosclerosis Risk in Communities (ARIC) Study, 14,280 middle-aged adults were categorized on the basis of estimated GFR >/=90, 60 to 89, and 15 to 59 ml/min per 1.73 m(2) for normal kidney function, mildly decreased kidney function, and stages 3 to 4 CKD, respectively. Incident PAD was defined as a new onset of ankle-brachial index <0.9 assessed at regular examinations, new intermittent claudication assessed by annual surveillance, or PAD-related hospital discharges. Incidence rates and relative risks (RR) for PAD were compared across these categories. During a mean follow-up time of 13.1 yr (186,616 person-years), 1016 participants developed PAD. The incidence rates per 1000 person-years were 4.7, 4.9, and 8.6 for the normal kidney function, mildly decreased kidney function, and CKD groups, respectively. Compared with participants with normal kidney function, the age-, gender-, race-, and ARIC field center-adjusted RR for PAD was 1.04 (95% confidence interval [CI] 0.91 to 1.18) for those with mildly decreased kidney function and 1.82 (95% CI 1.34 to 2.47) for those with CKD. After additional adjustment for cardiovascular disease risk factors, an increase in risk for incident PAD still was observed in participants with CKD, with a multivariable adjusted RR of 1.56 (95% CI 1.13 to 2.14). Patients with CKD are at increased risk for incident PAD. Development of strategies for screening and prevention of PAD in this high-risk population seems warranted.
Systematic Review: Glucose Control and Cardiovascular Disease in Type 2 Diabetes
Authors: Tanika N. Kelly
Journal: Annals of Internal Medicine (2009)

Background: Results from clinical trials examining the effect of intensive glucose control on cardiovascular disease have been conflicting. Purpose: To summarize clinical benefits and harms of intensive versus conventional glucose control for adults with type 2 diabetes. Data Sources: Studies were retrieved by systematically searching the MEDLINE database (January 1950 to April 2009) with no language restrictions. Study Selection: Two independent reviewers screened abstracts or full-text articles to identify randomized trials that compared clinical outcomes in patients with type 2 diabetes receiving intensive glucose control and those receiving conventional glucose control. Data Extraction: Two investigators independently abstracted data on study variables and outcomes, including severe hypoglycemia, cardiovascular disease, and all-cause mortality. Data Synthesis: 5 trials involving 27 802 adults were included. Intensive glucose targets were lower in the 3 most recent trials. Summary analyses showed that compared with conventional control, intensive glucose control reduced the risk for cardiovascular disease (relative risk [RR], 0.90 [95% CI, 0.83 to 0.98]; risk difference per 1000 patients per 5 years [RD], −15 [CI, −24 to −5]) but not cardiovascular death (RR, 0.97 [CI, 0.76 to 1.24]; RD, −3 [CI, −14 to 7]) or all-cause mortality (RR, 0.98 [CI, 0.84 to 1.15]; RD, −4 [CI, −17 to 10]). Intensive glucose control increased the risk for severe hypoglycemia (RR, 2.03 [CI, 1.46 to 2.81]; RD, 39 [CI, 7 to 71]). As was seen in the overall analyses, pooled findings from the early and more recent trials showed that intensive glucose control reduced the risk for cardiovascular disease and increased the risk for severe hypoglycemia. Limitation: Summary rather than individual data were pooled across trials. Conclusion: Intensive glucose control reduced the risk for some cardiovascular disease outcomes (such as nonfatal myocardial infarction), did not reduce the risk for cardiovascular death or all-cause mortality, and increased the risk for severe hypoglycemia.
Potent Antitumor Activity of Interleukin-27
Authors: Masayuki Hisada, Sadahiro Kamiya, Koji Fujita, Maria Laura Belladonna, Tatuya Aoki, Yasuhisa Koyanagi, Junichiro Mizuguchi, Takayuki Yoshimoto
Journal: Cancer Research (2004)

Abstract Although much promising data that interleukin (IL)-12 could be a powerful therapeutic agent against cancer were reported in animal models, its excessive toxicity has become a problem for its clinical application. IL-27 is a novel IL-12 family member that plays a role in the early regulation of T helper cell 1 initiation, including induction of T-bet and IL-12 receptor β2 expression. In the present study, we have evaluated the antitumor activity of IL-27 against a murine tumor model of colon carcinoma C26. C26 cells, which were transduced with the single-chain IL-27 cDNA and became secreting IL-27 (C26-IL-27), exhibited minimal tumor growth in vivo, and all of the mice inoculated with these cells survived healthily with complete tumor remission. Inoculation of mice with C26-IL-27 induced enhanced IFN-γ production and cytotoxic T-lymphocyte activity against C26 tumor in spleen cells. Recovered mice from the inoculation showed a tumor-specific protective immunity to the following challenge with parental C26 tumor. The antitumor activity of IL-27 was almost diminished in nude mice, and depletion of CD8+ T cells and neutralization of IFN-γ in immunocompetent mice reduced greatly the antitumor activity. Moreover, the antitumor activity was abolished in T-bet-deficient mice, whereas it was observed unexpectedly in mice deficient of signal transducer and activator of transcription (STAT) 4. These results suggest that IL-27 has potent abilities to induce tumor-specific antitumor activity and protective immunity and that the antitumor activity is mediated mainly through CD8+ T cells, IFN-γ, and T-bet but not through STAT4.
Polymorphisms Identified through Genome-Wide Association Studies and Their Associations with Type 2 Diabetes in Chinese, Malays, and Asian-Indians in Singapore
Authors: Jonathan T. Tan, Daniel P. K. Ng, Siti Nurbaya, Sandra Ye, Xiu Li Lim, Helen Leong, Lin Tze Seet, Wei Fong Siew, Winston Kon, Tien Yin Wong, Seang Mei Saw, Tin Aung, Kee Seng Chia, Jeannette Lee, Suok Kai Chew, Mark Seielstad, E. Shyong Tai
Journal: Endocrine Reviews (2009)

Context: Novel type 2 diabetes mellitus (T2DM) susceptibility loci, identified through genome-wide association studies (GWAS), have been replicated in many European and Japanese populations.However, the association in other East Asian populations is less well characterized.Objective: To examine the effects of SNPs in CDKAL1, CDKN2A/B, IGF2BP2, HHEX, SLC30A8, PKN2, LOC387761, and KCNQ1 on risk of T2DM in Chinese, Malays, and Asian-Indians in Singapore.Design: We genotyped these candidate single-nucleotide polymorphisms (SNPs) in subjects from three major ethnic groups in Asia, namely, the Chinese (2196 controls and 1541 cases), Malays (2257 controls and 1076 cases), and Asian-Indians (364 controls and 246 cases).We also performed a metaanalysis of our results with published studies in East Asians.Results: In Chinese, SNPs in CDKAL1 [odds ratio (OR) ϭ 1.19; P ϭ 2 ϫ 10 Ϫ4 ], HHEX (OR ϭ 1.15; P ϭ 0.013), and KCNQ1 (OR ϭ 1.21; P ϭ 3 ϫ 10 Ϫ4 ) were significantly associated with T2DM.Among Malays, SNPs in CDKN2A/B (OR ϭ 1.22; P ϭ 3.7 ϫ 10 Ϫ4 ), HHEX (OR ϭ 1.12; P ϭ 0.044), SLC30A8 (OR ϭ 1.12; P ϭ 0.037), and KCNQ1 (OR ϭ 1.19 -1.25; P ϭ 0.003-2.5 ϫ 10 Ϫ4 ) showed significant association with T2DM.The combined analysis of the three ethnic groups revealed significant associations between SNPs in CDKAL1 (OR ϭ 1.13; P ϭ 3 ϫ 10 Ϫ4 ), CDKN2A/B (OR ϭ 1.16; P ϭ 9 ϫ 10 Ϫ5 ), HHEX (OR ϭ 1.14; P ϭ 6 ϫ 10 Ϫ4 ), and KCNQ1 (OR ϭ 1.16 -1.20; P ϭ 3 ϫ 10 Ϫ4 to 3 ϫ 10 Ϫ6 ) with T2DM.SLC30A8 (OR ϭ 1.06; P ϭ 0.039) showed association only after adjustment for gender and body mass index.Metaanalysis with data from other East Asian populations showed similar effect sizes to those observed in populations of European ancestry.Conclusions: SNPs at T2DM susceptibility loci identified through GWAS in populations of European ancestry show similar effects in Asian populations.Failure to detect these effects across different populations may be due to issues of power owing to limited sample size, lower minor allele frequency, or differences in genetic effect sizes.