tbuckley/cabot-search huggingface dataset:
Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome
Authors: Tetsuya Niihori, Yoko Aoki, Yoko Narumi, Giovanni Neri, Hélène Cavé, Alain Verloes, Nobuhiko Okamoto, Raoul C M Hennekam, Gabriele Gillessen-Kaesbach, Dagmar Wieczorek, Maria Ines Kavamura, Kenji Kurosawa, Hirofumi Ohashi, Louise Wilson, Delphine Heron, Dominique Bonneau, Giuseppina Corona, Tadashi Kaname, Kenji Naritomi, Clarisse Baumann, Naomichi Matsumoto, Kumi Kato, Shigeo Kure, Yoichi Matsubara
Journal: Nature Genetics (2006)
Redox modification of ryanodine receptors underlies calcium alternans in a canine model of sudden cardiac death
Authors: Andriy E. Belevych, Dmitry Terentyev, Serge Viatchenko-Karpinski, Radmila Terentyeva, Arun Sridhar, Yoshinori Nishijima, Lance D. Wilson, Arturo J. Cardounel, Kenneth R. Laurita, Cynthia A. Carnes, George E. Billman, Sandor Gyorke
Journal: Cardiovascular Research (2009)

AimsAlthough cardiac alternans is a known predictor of lethal arrhythmias, its underlying causes remain largely undefined in disease settings. The potential role of, and mechanisms responsible for, beat-to-beat alternations in the amplitude of systolic Ca2+ transients (Ca2+ alternans) was investigated in a canine post-myocardial infarction (MI) model of sudden cardiac death (SCD).
Patterns of Gene Expression That Characterize Long-term Survival in Advanced Stage Serous Ovarian Cancers
Authors: Andrew Berchuck, Edwin S. Iversen, Johnathan M. Lancaster, Jennifer Pittman, Jingqin Luo, Paula Lee, Susan Murphy, Holly K. Dressman, Phillip G. Febbo, Mike West, Joseph R. Nevins, Jeffrey R. Marks
Journal: Clinical Cancer Research (2005)

Abstract Purpose: A better understanding of the underlying biology of invasive serous ovarian cancer is critical for the development of early detection strategies and new therapeutics. The objective of this study was to define gene expression patterns associated with favorable survival. Experimental Design: RNA from 65 serous ovarian cancers was analyzed using Affymetrix U133A microarrays. This included 54 stage III/IV cases (30 short-term survivors who lived &amp;lt;3 years and 24 long-term survivors who lived &amp;gt;7 years) and 11 stage I/II cases. Genes were screened on the basis of their level of and variability in expression, leaving 7,821 for use in developing a predictive model for survival. A composite predictive model was developed that combines Bayesian classification tree and multivariate discriminant models. Leave-one-out cross-validation was used to select and evaluate models. Results: Patterns of genes were identified that distinguish short-term and long-term ovarian cancer survivors. The expression model developed for advanced stage disease classified all 11 early-stage ovarian cancers as long-term survivors. The MAL gene, which has been shown to confer resistance to cancer therapy, was most highly overexpressed in short-term survivors (3-fold compared with long-term survivors, and 29-fold compared with early-stage cases). These results suggest that gene expression patterns underlie differences in outcome, and an examination of the genes that provide this discrimination reveals that many are implicated in processes that define the malignant phenotype. Conclusions: Differences in survival of advanced ovarian cancers are reflected by distinct patterns of gene expression. This biological distinction is further emphasized by the finding that early-stage cancers share expression patterns with the advanced stage long-term survivors, suggesting a shared favorable biology.
Photochemically induced colonic ischaemic lesions: a new model of ischaemic colitis in rats
Authors: Y Yano, H Yao, K Aoyagi, K Kawakubo, S Nakamura, K Doi, S Ibayashi, M Fujishima
Journal: Gut (1997)

Recent clinical studies suggest that ischaemic colitis is caused by a microcirculatory disturbance that involves thrombosis of the colon.To establish a new model of photochemically induced ischaemic colitis in rats.Thirty male Wistar rats were anaesthetised with amobarbital, the femoral veins were cannulated and laparotomies were performed. The serosal surface of the proximal colon was irradiated by using a krypton laser (wavelength 568 nm, 20 mW) for four minutes. An intravenous infusion of a photosensitising dye, rose bengal (20 mg/kg body weight), was administered over 90 seconds, beginning at the start of irradiation. Rats were killed immediately (n = 4), 12 hours (n = 2), 24 hours (n = 10), three days (n = 4), seven days (n = 4), 14 days (n = 2), or 28 days (n = 2) after irradiation. Two control rats received laser irradiation without dye infusion. Specimens of the irradiated sites were examined by using histopathology.Localised ulcers of the colon were present in rats killed at 12 hours, 24 hours, three days, and seven days after irradiation. Microscopy findings were consistent with the features of human ischaemic colitis. Reproducible ulcerative lesions were produced by photothrombosis of microvessels in the colon.This model may be useful for further investigation of the pathophysiology of ischaemic colitis.
Fifty-five per cent return to competitive sport following anterior cruciate ligament reconstruction surgery: an updated systematic review and meta-analysis including aspects of physical functioning and contextual factors
Authors: Clare L Ardern, Nicholas F Taylor, Julian A Feller, Kate E Webster
Journal: British Journal of Sports Medicine (2014)

The aim of this study was to update our original systematic review of return to sport rates following anterior cruciate ligament (ACL) reconstruction surgery.Electronic databases were searched from April 2010 to November 2013 for articles reporting the number of patients returning to sport following ACL reconstruction surgery. Return to sport rates, physical functioning and contextual data were extracted and combined using random-effects meta-analyses. Data from the original review (articles published up to April 2010) were combined with data from the updated search.Sixty-nine articles, reporting on 7556 participants, were reviewed. On average, 81% of people returned to any sport, 65% returned to their preinjury level of sport and 55% returned to competitive level sport after surgery. Symmetrical hopping performance (d=0.3) and the contextual factors of younger age (d=-0.3), male gender (OR=1.4), playing elite sport (OR=2.5) and having a positive psychological response (d=0.3) favoured returning to the preinjury level sport. Receiving a hamstring tendon autograft favoured returning to competitive level sport (OR=2.4), whereas receiving a patellar tendon autograft favoured returning to the preinjury level sport (OR=1.2).Returning to sport varied according to different physical functioning and contextual factors, which could warrant additional emphasis in postoperative rehabilitation programmes to maximise participation.
A Phylum-Level Bacterial Phylogenetic Marker Database
Authors: Zhang Wang, Martin Wu
Journal: Molecular Biology and Evolution (2013)

Large-scale, genome-level molecular phylogenetic analyses present both opportunities and challenges for bacterial evolutionary and ecological studies. We constructed a phylum-level bacterial phylogenetic marker database by surveying all complete bacterial genomes and identifying single-copy genes that were widely distributed in each of the 20 bacterial phyla. We showed that phylum trees made using these markers were highly resolved and were more robust than the bacterial genome tree based on 31 universal bacterial marker genes. In addition, using the Global Ocean Sampling data set as an example, we demonstrated that the expanded marker database greatly increased the power of metagenomic phylotyping. We incorporated the database into an automated phylogenomic inference application (Phyla-AMPHORA) and made it publicly available. We believe that this centralized resource should have broad applicability in bacterial systematics, phylogenetics, and metagenomic studies.
Double-Blind, Placebo-Controlled Comparison of Intramuscular Olanzapine and Intramuscular Haloperidol in the Treatment of Acute Agitation in Schizophrenia
Authors: P Wright, M Birkett, S R David, K Meehan, I Ferchland, K J Alaka, J C Saunders, J Krueger, P Bradley, L San, M Bernardo, M Reinstein, A Breier
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The authors evaluated the comparative efficacy and safety of intramuscular olanzapine, intramuscular haloperidol, and intramuscular placebo for the treatment of acute agitation in schizophrenia. METHOD: Hospitalized patients with schizophrenia received one to three injections of intramuscular olanzapine, 10 mg, intramuscular haloperidol, 7.5 mg, or intramuscular placebo over a 24-hour period. Agitation was measured with the excited component of the Positive and Negative Syndrome Scale and two additional scales. RESULTS: According to scores on the excited component of the Positive and Negative Syndrome Scale, both intramuscular olanzapine and intramuscular haloperidol reduced agitation significantly more than intramuscular placebo 2 and 24 hours following the first injection. Intramuscular olanzapine reduced agitation significantly more than intramuscular haloperidol 15, 30, and 45 minutes following the first injection. No patients treated with intramuscular olanzapine experienced acute dystonia, compared with 7% of those who were treated with intramuscular haloperidol. No significant QTc interval changes were observed in any patients. CONCLUSIONS: Intramuscular olanzapine represents a rapid, effective, and safe treatment for acute agitation in schizophrenia.
BCR–ABL Transcript Dynamics Support the Hypothesis That Leukemic Stem Cells Are Reduced during Imatinib Treatment
Authors: Andrew M. Stein, Dean Bottino, Vijay Modur, Susan Branford, Jaspal Kaeda, John M. Goldman, Timothy P. Hughes, Jerald P. Radich, Andreas Hochhaus
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Imatinib induces a durable response in most patients with Philadelphia chromosome–positive chronic myeloid leukemia, but it is currently unclear whether imatinib reduces the leukemic stem cell (LSC) burden, which may be an important step toward enabling safe discontinuation of therapy. In this article, we use mathematical models of BCR–ABL levels to make inferences on the dynamics of LSCs. Experimental Design: Patients with at least 1 BCR–ABL transcript measurement on imatinib were included (N = 477). Maximum likelihood methods were used to test 3 potential hypotheses of the dynamics of BCR–ABL transcripts on imatinib therapy: (i) monoexponential, in which there is little, if any, decline in BCR–ABL transcripts; (ii) biexponential, in which patients have a rapid initial decrease in BCR–ABL transcripts followed by a more gradual response; and (iii) triexponential, in which patients first exhibit a biphasic decline but then have a third phase when BCR–ABL transcripts increase rapidly. Results: We found that most patients treated with imatinib exhibit a biphasic decrease in BCR–ABL transcript levels, with a rapid decrease during the first few months of treatment, followed by a more gradual decrease that often continues over many years. Conclusions: We show that the only hypothesis consistent with current data on progenitor cell turnover and with the long-term, gradual decrease in the BCR–ABL levels seen in most patients is that these patients exhibit a continual, gradual reduction of the LSCs. This observation may explain the ability to discontinue imatinib therapy without relapse in some cases. Clin Cancer Res; 17(21); 6812–21. ©2011 AACR.
Aldose Reductase Genotypes and Cardiorenal Complications
Authors: Wing-Yee So, Ying Wang, Maggie C.Y. Ng, Xilin Yang, Ronald C.W. Ma, Vincent Lam, Alice P.S. Kong, Peter C.Y. Tong, Juliana C.N. Chan
Journal: Diabetes Care (2008)

We report the independent risk association of type 2 diabetic nephropathy with the z-2 allele of the 5'-(CA)(n) microsatellite and C-106T promoter polymorphisms of the aldose reductase gene (ALR2) using a case-control design. In this expanded cohort, we examined their predictive roles on new onset of cardiorenal complications using a prospective design.In this 8-year prospective cohort of 1,074 type 2 diabetic patients (59% male, median age 61 years; disease duration 7 years) with an observation period of 8,592 person-years, none had clinical evidence of coronary heart disease (CHD) or chronic kidney disease at recruitment. The renal end point was defined as new onset of estimated glomerular filtration rate <60 ml/min per 1.72 m(2) or hospitalizations with dialysis or death due to renal disease, and CHD was defined as hospitalizations with myocardial infarction, ischemic heart disease, or related deaths.After controlling for baseline risk factors and use of medications, we found that the ALR2 z-2 allele of (CA)(n) microsatellite carriers had increased risk of renal (hazard ratio 1.53 [95% CI 1.14-2.05], P = 0.005) or combined cardiorenal (1.31 [1.01-1.72], P = 0.047) end points. Carriers of the ALR2 C-106T polymorphism also had increased risk of renal (1.54 [1.15-2.07], P = 0.004) and cardiorenal (1.49 [1.14-1.95], P = 0.004) end points. Compared with noncarriers, patients with two risk-conferring genotypes had a twofold increased risk of renal (2.41 [1.57-3.70], P < 0.001) and cardiorenal (1.94 [1.29-2.91], P = 0.002) end points.In Chinese type 2 diabetic patients, genetic polymorphisms of ALR2 independently predicted new onset of renal and cardiorenal end points, with the latter being largely mediated through renal disease.
Peroxisome Proliferator-Activated Receptor Activators Inhibit Thrombin-Induced Endothelin-1 Production in Human Vascular Endothelial Cells by Inhibiting the Activator Protein-1 Signaling Pathway
Authors: Philippe Delerive, Françoise Martin-Nizard, Giulia Chinetti, François Trottein, Jean-Charles Fruchart, Jamila Najib, Patrick Duriez, Bart Staels
Journal: Circulation Research (1999)

Abstract —Endothelin-1 (ET-1), a 21-amino acid vasoactive peptide mainly produced by vascular endothelial cells, is involved in the regulation of vascular tone and smooth muscle cell proliferation. Peroxisome proliferator-activated receptors (PPARs), key players in lipid and glucose metabolism, have been implicated in metabolic disorders that are predisposing to atherosclerosis. Because of the potential role of ET-1 in vascular disorders such as hypertension and atherosclerosis, we investigated the regulation of ET-1 expression by PPAR activators. Western blot and reverse transcription–polymerase chain reaction analyses demonstrated that both PPARα and PPARγ are expressed in human coronary artery endothelial cells as well as in endothelial cell lines such as HMEC-1 and ECV304. In bovine aortic endothelial cells and HMEC-1 cells, both PPARα and PPARγ ligands inhibited thrombin-induced ET-1 secretion, whereas basal ET-1 secretion was only slightly suppressed. Reverse transcription–polymerase chain reaction experiments showed that this inhibition of ET-1 production occurs at the gene expression level. Using transient transfection assays, we demonstrated that PPARs downregulate thrombin-activated transcription of the human ET-1 promoter. Transactivation studies with c-Jun and c-Fos expression plasmids indicated that PPARs negatively interfere with the activator protein-1 signaling pathway, which mediates thrombin activation of ET-1 gene transcription. Furthermore, electrophoretic mobility shift assays demonstrated that PPAR activators reduce the thrombin-stimulated binding activity of bovine aortic endothelial cell nuclear extracts as well as c-Jun binding to an activator protein-1 consensus site. Taken together, these data indicate that (1) both PPARα and PPARγ are expressed in human vascular endothelial cells and (2) PPAR activators inhibit thrombin-induced ET-1 biosynthesis, indicating a novel role for PPARs in vascular endothelial function.
Estrogen, Estrogen Plus Progestin Therapy, and Risk of Breast Cancer
Authors: Graham A. Colditz
Journal: Clinical Cancer Research (2005)

Abstract Epidemiologic evidence relating use of postmenopausal hormones to risk of breast cancer by nature relies on trends in prescribing practices. Data on the adverse effect of combination estrogen plus progestin used for long durations has only become available over the past decade. Evidence is reviewed relating estrogen alone and estrogen plus progestin to increased risk of breast cancer. Whereas current evidence indicates that longer duration of use increases risk of invasive breast cancer regardless of formulation, the rate of increase in risk is greater for combination estrogen plus progestin therapy. Although data are limited, continuous combined therapy and sequential therapy seem to have comparable impact on breast cancer risk. Combination therapy is more strongly related to lobular breast cancer than is estrogen alone. Unresolved issues remain about dose of estrogen and progestin in relation to risk, and about identification of women for whom short-term use to relieve menopausal symptoms may be safe and effective.
Hemophilia A in a Phenotypically Normal Female with XX/XO Mosaicism
Authors: Gerald S. Gilchrist, Denman Hammond, John Melnyk
Journal: New England Journal of Medicine (1965)

HEMOPHILIA in females has been the subject of a number of reports in recent years.1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Excluding patients who conform to the classic sex-linked mode of transmission and are truly homozygous for the hemophilia gene,5 , 9 , 11 , 12 , 14 , 17 a residual group of apparent females who exhibit varying degrees of clinical disease remains. The deficiency of antihemophilic globulin (AHG, factor VIII) in these persons who are assumed to be heterozygotes has generally been explained on the basis of mutation in the normal X chromosome. Five such persons have had chromosome analyses performed,4 , 6 , 8 , 10 , 16 and in only 110 was an abnormal karyotype detected.It is the purpose . . .
Effect of intense wrestling exercise on leucocytes and adhesion molecules in adolescent boys
Authors: D Nemet, P J Mills, D M Cooper
Journal: British Journal of Sports Medicine (2004)

Background: In adults, exercise is a powerful and natural stimulator of immune cells and adhesion molecules. Far less is known about exercise responses during childhood and adolescence and whether or not exercise in “real life” activities of healthy adolescents influences immune responses. Objective: To determine if strenuous exercise leads to significant changes in leucocyte number and adhesion molecule expression in adolescent boys. Methods: Eleven healthy, high school boys, aged 14–18.5 years, performed a single, typical, 1.5 hour wrestling practice session. Blood was sampled before and after the session. Flow cytometry was used to evaluate changes in immune responses. Results: The exercise led to significant (p&lt;0.05) and robust increases in granulocytes, monocytes, and all lymphocyte subpopulations. The most significant changes were observed for natural killer cells (p&lt;0.0005). The number of T cytotoxic and T helper cells expressing CD62L increased significantly (p&lt;0.002 and p&lt;0.0005 respectively), as did the number of T cytotoxic and T helper cells not expressing CD62L (p&lt;0.003 and p&lt;0.009 respectively). The density of CD62L on lymphocytes decreased significantly with exercise (p&lt;0.0005), whereas CD11a (p&lt;0.01) and CD54 (p&lt;0.01) increased. Conclusions: The data show that an intense wrestling bout in adolescent boys leads to profound stimulation of the immune system. The role of these common changes in overall immune status and the development of the immune and haemopoietic systems has yet to be determined.
Musculoskeletal and Neurologic Outcomes in Patients with Previously Treated Lyme Disease
Authors: Nancy A. Shadick, Charlotte B. Phillips, Oliver Sangha, Eric L. Logigian, Richard F. Kaplan, Elizabeth A. Wright, Anne H. Fossel, Karin Fossel, Victor Berardi, Robert A. Lew, Matthew H. Liang
Journal: Annals of Internal Medicine (1999)

Background: Previous follow-up studies of patients with Lyme disease suggest that disseminated infection may be associated with long-term neurologic and musculoskeletal morbidity. Objective: To determine clinical and functional outcomes in persons who were treated for Lyme disease in the late 1980s. Design: Population-based, retrospective cohort study. Setting: Nantucket Island, Massachusetts. Participants: 186 persons who had a history of Lyme disease (case-patients) and 167 persons who did not (controls). Measurements: Standardized medical history, physical examination, functional status measure (Medical Outcomes Study 36-Item Short Form Health Survey [SF-36]), mood state assessment (Profile of Mood States), neurocognitive tests, and serologic examination. Results: The prevalence of Lyme disease among adults on Nantucket Island was estimated to be 14.3% (95% CI, 9.3% to 19.1%). In multivariate analyses, persons with previous Lyme disease (mean time from infection to study evaluation, 6.0 years) had more joint pain (odds ratio for having joint pain in any joint, 2.1 [CI, 1.2 to 3.5]; P = 0.007), more symptoms of memory impairment (odds ratio for having any memory problem, 1.9 [CI, 1.1 to 3.5]; P = 0.003), and poorer functional status due to pain (odds ratio for 1 point on the SF-36 scale, 1.02 [CI, 1.01 to 1.03]; P < 0.001) than persons without previous Lyme disease. However, on physical examination, case-patients and controls did not differ in musculoskeletal abnormalities, neurologic abnormalities, or neurocognitive performance. Persons with previous Lyme disease who had persistent symptoms after receiving treatment (n = 67) were more likely than those who had completely recovered to have had fever, headache, photosensitivity, or neck stiffness during their acute illness (87% compared with 13%; odds ratio, 2.4 [CI, 1.0 to 5.5]; P = 0.045); however, the performance of the two groups on neurocognitive tests did not significantly differ. Conclusions: Because persons with previous Lyme disease exhibited no sequelae on physical examination and neurocognitive tests a mean of 6.0 years after infection, musculoskeletal and neurocognitive outcomes seem to be favorable. However, long-term impairment of functional status can occur.