tbuckley/cabot-search huggingface dataset:
Long-Term Survival After Surgical Treatment of Patients With Takayasu’s Arteritis
Authors: Tetsuro Miyata, Osamu Sato, Hiroyuki Koyama, Hiroshi Shigematsu, Yusuke Tada
Journal: Circulation (2003)

Background— Surgical interventions have been performed to ameliorate the complications of Takayasu’s arteritis. However, the efficacy of surgery to increase long-term survival has not been established. Methods and Results— A retrospective review was performed on the survival of 106 consecutive patients with Takayasu’s arteritis who underwent surgical treatment during the past 40 years. Their ages ranged from 5 to 69 years (mean±SEM, 31.7±1.3 years). Survival was compared with the reported results of medically treated patients according to Ishikawa’s prognostic classification. There were 12 hospital deaths, and the remaining 94 patients were followed up from 8 months to 41.8 years (mean, 19.8 years). A serious long-term complication was anastomotic aneurysm, with a cumulative incidence at 20 years of 13.8%. Thirty-one late deaths were observed, and the major cause was congestive heart failure. The overall cumulative survival rate at 20 years was 73.5%. The prognostic classification by Ishikawa had little influence on the survival of surgically treated patients. For stage 3 patients, surgery seemed to increase survival; however, surgery-related complications conversely decreased the survival of stage 1 patients. Conclusions— Surgery seems to increase the long-term survival of patients with stage 3 Takayasu’s arteritis, whereas conservative treatment is recommended for those with stage 1 or 2 disease. An anastomotic aneurysm may occur at any time after surgery, and regular follow-up using imaging modalities such as multi-detector CT, MRI, or ultrasonography at least once every several years for the rest of the patient’s life is mandatory for the early detection of anastomotic aneurysm.
p21/Cip1 and p27/Kip1 Are Essential Molecular Targets of Inositol Hexaphosphate for Its Antitumor Efficacy against Prostate Cancer
Authors: Srirupa Roy, Mallikarjuna Gu, Kumaraguruparan Ramasamy, Rana P. Singh, Chapla Agarwal, Sunitha Siriwardana, Robert A. Sclafani, Rajesh Agarwal
Journal: Cancer Research (2009)

Inositol hexaphosphate (IP6) causes G(1) arrest and increases cyclin-dependent kinase inhibitors p21/Cip1 and p27/Kip1 protein levels in human prostate cancer (PCa) DU145 cells lacking functional p53. However, whether cyclin-dependent kinase inhibitor I induction by IP6 plays any role in its antitumor efficacy is unknown. Herein, we observed that either p21 or p27 knockdown by small interfering RNA has no considerable effect on IP6-induced G(1) arrest, growth inhibition, and death in DU145 cells; however, the simultaneous knockdown of both p21 and p27 reversed the effects of IP6. To further confirm these findings both in vitro and in vivo, we generated DU145 cell variants with knockdown levels of p21 (DU-p21), p27 (DU-p27), or both (DU-p21+p27) via retroviral transduction of respective short hairpin RNAs. Knocking down p21 or p27 individually did not alter IP6-caused cell growth inhibition and G(1) arrest; however, their simultaneous ablation completely reversed the effects of IP6. In tumor xenograft studies, IP6 (2% w/v, in drinking water) caused a comparable reduction in tumor volume (40-46%) and tumor cell proliferation (26-28%) in DU-EV (control), DU-p21, and DU-p27 tumors but lost most of its effect in DU-p21+p27 tumors. IP6-caused apoptosis also occurred in a Cip/Kip-dependent manner because DU-p21+p27 cells were completely resistant to IP6-induced apoptosis both in cell culture and xenograft. Together, these results provide evidence, for the first time, of the critical role of p21 and p27 in mediating the anticancer efficacy of IP6, and suggest their redundant role in the antiproliferative and proapoptotic effects of IP6 in p53-lacking human PCa cells, both in vitro and in vivo.
Why Do Nonwhite Patients Undergo Amputation More Commonly Than White Patients?
Authors: Karl A. Illig
Journal: JAMA Surgery (2013)

There is a compelling amount of data showing that amputation and revascularization rates between white and nonwhite patients are different. What accounts for this? The current analysis suggests that access to care, socioeconomic status, and clinical category of disease at presentation do not account for such differences.1 In their discussion, the authors suggest 3 general factors to consider: (1) differing access to care, (2) patient factors such as noncompliance, and (3) physician factors including bias and prejudice; however, they ultimately cite reasonably good arguments against most. Nowhere do they claim that health care provider bias is the reason, but this seems to be the only factor that cannot be excluded. There isa fourthpossibleexplanation,especiallyas theothers do not seem to be causative: genetic differences in the behavior of peripheral vascular disease between groups. While the authorspointedout that dividingpeople into separate categories (race) is a social construct, there are clearly biological differences between any 2 broadly defined groups (eg, resistance to malaria, response to alcohol, behavior of breast cancer, and response to certain drugs, in addition to the amount of melanin in the skin). What if there were differences in the behavior, composition, or anatomic patterns of atherosclerosis itself? In other words, 2 people may have the same access tocare, socioeconomicstatus,andcompliance,but (evenwithin the same clinical class at presentation) one has disease that is more often amenable to bypasswhen symptomatic,while the otherhasagreaterchanceofpresentingwithanatomicallynonreconstructable occlusion—all because of genetic factors. It is politically dangerous to raise the issue of consistent biologic variability between groups, but such variability unequivocally exists for certain genetically determined entities. If we ignore this issue, we run the risk of doing just what we are trying to avoid—giving one group of patients inferior carebecausewehavenot recognizedthe truecauseof theproblem. Durazzo and colleagues1 have shown that it is not access to care or economic factors that account for the (real) differences in amputation rates—thus,weare leftwith either health care provider bias or genetic differences in the disease process itself. It may be the former, but we must investigate the latter to provide the best possible care for all our patients.
Sarcomeric proteins and inherited cardiomyopathies
Authors: S. Morimoto
Journal: Cardiovascular Research (2007)

Over the last two decades, a large number of mutations have been identified in sarcomeric proteins as a cause of hypertrophic, dilated or restrictive cardiomyopathy. Functional analyses of mutant proteins in vitro have revealed several important functional changes in sarcomeric proteins that might be primarily involved in the pathogenesis of each cardiomyopathy. Creation of transgenic or knock-in animals expressing mutant proteins in their hearts confirmed that these mutations in genes for sarcomeric proteins induced distinct types of cardiomyopathies and provided useful animal models to explore the molecular pathogenic mechanisms and potential therapeutics of cardiomyopathy in vivo. In this review, I discuss the functional consequences of mutations in different sarcomeric proteins found in hypertrophic, dilated, and restrictive cardiomyopathies in conjunction with their effects on cardiac structure and function in vivo and their possible molecular and cellular mechanisms, which underlie the pathogenesis of these inherited cardiomyopathies.
Endothelium-Derived Nitric Oxide Plays a Larger Role in Pulmonary Veins Than in Arteries of Newborn Lambs
Authors: Yuansheng Gao, Haiyan Zhou, J. Usha Raj
Journal: Circulation Research (1995)

Abstract In perinatal lungs, veins contribute substantially to total pulmonary vascular resistance. The present study was designed to determine the role of endothelium-derived nitric oxide (EDNO) in modulating the responsiveness of pulmonary veins and arteries in newborn lambs. Fourth-order pulmonary arterial and venous rings of newborn lambs were suspended in organ chambers filled with modified Krebs-Ringer bicarbonate solution (95% O 2 /5% CO 2 , 37°C), and their isometric force was measured. Nitro- l -arginine had no effect on the resting tension of pulmonary arteries but caused an endothelium-dependent contraction of pulmonary veins. During contraction to endothelin-1 or U46619, acetylcholine, bradykinin, and calcium ionophore A23187 induced larger endothelium-dependent relaxation in pulmonary veins than in arteries. The endothelium-dependent relaxation of pulmonary vessels was abolished by nitro- l -arginine. In vessels without endothelium, nitric oxide induced significantly greater relaxation in pulmonary veins than in arteries. All vessels relaxed similarly to 8-bromo-cGMP. Radioimmunoassay showed that the basal level of intracellular cGMP of pulmonary veins with endothelium was higher than that of arteries with endothelium. Acetylcholine, bradykinin, and calcium ionophore A23187 induced a significantly larger endothelium-dependent increase in the intracellular content of cGMP in pulmonary veins than in arteries. In vessels without endothelium, nitric oxide induced a larger increase in cGMP content in pulmonary veins than in arteries. The present study suggests that EDNO may play a larger role in modulation of pulmonary venous than arterial reactivity, which may be mainly due to a difference in the activity of soluble guanylate cyclase in vascular smooth muscle.
Amantadine triple therapy for non-responder hepatitis C patients. Clues for controversies (ANRS HC 03 BITRI)
Authors: Marianne Maynard, Pierre Pradat, François Bailly, Frédéric Rozier, Chantal Nemoz, Si Nafa Si Ahmed, Patrice Adeleine, Christian Trépo, and a French Multicenter Group
Journal: Journal of Hepatology (2005)
Myocardin-Related Transcription Factor A Mediates OxLDL-Induced Endothelial Injury
Authors: Fei Fang, Yuyu Yang, Zhibin Yuan, Yuqi Gao, Jiliang Zhou, Qi Chen, Yong Xu
Journal: Circulation Research (2011)

Atherosclerosis proceeds through a multistep reaction that begins with endothelial injury caused by a host of stress signals, among which oxidized low-density lipoprotein (oxLDL) plays a critical role. OxLDL disrupts normal functionality of the endothelium by upregulating adhesion molecules (eg, ICAM-1) and concomitantly downregulating endothelial nitric oxide synthase (eNOS) expression. The transcriptional modulator that mediates the cellular response to oxLDL remains largely obscure.Our goal was to determine whether myocardin-related transcription factor (MRTF)-A, a key protein involved in the transcriptional regulation of smooth muscle cell phenotype, is responsible for the endothelial injury by oxLDL, and, if so, how MRTF-A promotes the proatherogenic agenda initiated by oxLDL.OxLDL stimulated the expression of MRTF-A in endothelial cells as evidenced by Western blotting and immunofluorescence. Overexpression of MRTF-A synergistically enhanced the induction of ICAM-1 and suppression of eNOS by oxLDL. In contrast, disruption of MRTF-A, either by small interfering RNA or dominant negative mutation, abrogated the pathogenic program triggered by oxLDL. Finally, chromatin immunoprecipitation assays indicate that oxLDL preferentially augmented MRTF-A binding to ICAM-1 and eNOS promoters and that MRTF-A drove differential epigenetic alterations taking place on these promoters in response to oxLDL.Therefore, our data provide the first demonstration that MRTF-A is critically linked to pivotal pathophysiological events in the vascular endothelium.
Suicide and Cardiovascular Death after a Cancer Diagnosis
Authors: Fang Fang, Katja Fall, Murray A. Mittleman, Pär Sparén, Weimin Ye, Hans-Olov Adami, Unnur Valdimarsdóttir
Journal: New England Journal of Medicine (2012)

Receiving a diagnosis of cancer is a traumatic experience that may trigger immediate adverse health consequences beyond the effects of the disease or treatment.Using Poisson and negative binomial regression models, we conducted a historical cohort study involving 6,073,240 Swedes to examine the associations between a cancer diagnosis and the immediate risk of suicide or death from cardiovascular causes from 1991 through 2006. To adjust for unmeasured confounders, we also performed a nested, self-matched case-crossover analysis among all patients with cancer who died from suicide or cardiovascular diseases in the cohort.As compared with cancer-free persons, the relative risk of suicide among patients receiving a cancer diagnosis was 12.6 (95% confidence interval [CI], 8.6 to 17.8) during the first week (29 patients; incidence rate, 2.50 per 1000 person-years) and 3.1 (95% CI, 2.7 to 3.5) during the first year (260 patients; incidence rate, 0.60 per 1000 person-years). The relative risk of cardiovascular death after diagnosis was 5.6 (95% CI, 5.2 to 5.9) during the first week (1318 patients; incidence rate, 116.80 per 1000 person-years) and 3.3 (95% CI, 3.1 to 3.4) during the first 4 weeks (2641 patients; incidence rate, 65.81 per 1000 person-years). The risk elevations decreased rapidly during the first year after diagnosis. Increased risk was particularly prominent for cancers with a poor prognosis. The case-crossover analysis largely confirmed results from the main analysis.In this large cohort study, patients who had recently received a cancer diagnosis had increased risks of both suicide and death from cardiovascular causes, as compared with cancer-free persons. (Funded by the Swedish Council for Working Life and Social Research and others.).
Comparing Phylogeographic Hypotheses by Simulating DNA Sequences under a Spatially Explicit Model of Coalescence
Authors: Simon Dellicour, Chedly Kastally, Olivier J Hardy, Patrick Mardulyn
Journal: Molecular Biology and Evolution (2014)

Computer simulations of genetic data are increasingly used to investigate the impact of complex historical scenarios on patterns of genetic variation. Yet, in most empirical studies, relatively large portions of species ranges are often treated as panmictic populations, ignoring the underlying spatial context. In some cases, however, a more accurate spatial model is required. We use a spatially explicit model of coalescence (easily constructed by overlaying a two-dimensional grid on maps displaying an estimate of past and current species ranges) to evaluate the potential of several summary statistics to differentiate three typical phylogeographic scenarios. We first explore the variation of each summary statistic within the boundaries of each phylogeographic scenario, and identify those that appear most promising for a comparison of historical scenarios and/or to infer historical parameters. We then combine a selected set of summary statistics in a single chi-square statistic and evaluate whether it can be used to differentiate past geographic fragmentation or range expansion from a simple scenario of isolation by distance. We also investigate the benefits of using a spatially explicit model by comparing its performance to alternative models that are less spatially explicit (lower geographic resolution). The results identify conditions in which each summary statistic is useful to infer the evolution of a species range, and allow us to validate our spatially explicit model of coalescence and our procedure to compare simulated and observed sequence data. We also provide a detailed description of the spatially explicit model of coalescence used, which is currently lacking.
Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial
Authors: W. Reinisch, W. J. Sandborn, D. W. Hommes, G. D'Haens, S. Hanauer, S. Schreiber, R. Panaccione, R. N. Fedorak, M. B. Tighe, B. Huang, W. Kampman, A. Lazar, R. Thakkar
Journal: Gut (2011)

<h3>Objective</h3> The aim of this study was to assess the efficacy and safety of adalimumab (ADA), a recombinant human monoclonal antibody against tumour necrosis factor α (TNF), for the induction of clinical remission in anti-TNF naïve patients with moderately to severely active ulcerative colitis. <h3>Methods</h3> This 8-week, multicentre, randomised, double-blind, placebo-controlled study (NCT00385736), conducted at 94 centres in North America and Europe, enrolled ambulatory adult patients with Mayo score of ≥6 points and endoscopic subscore of ≥2 points despite treatment with corticosteroids and/or immunosuppressants. Under the original study protocol, 186 patients were randomised (1:1) to subcutaneous treatment with ADA160/80 (160 mg at week 0, 80 mg at week 2, 40 mg at weeks 4 and 6) or placebo. Subsequently, at the request of European regulatory authorities, the protocol was amended to include a second induction group (ADA80/40: 80 mg at week 0, 40 mg at weeks 2, 4 and 6). The primary efficacy endpoint was clinical remission (Mayo score ≤2 with no individual subscore &gt;1) at week 8, assessed in 390 patients randomised (1:1:1) to ADA160/80, ADA80/40, or placebo. Safety was assessed in all enrolled patients. Patients, study site personnel, investigators, and the sponsor were blinded to treatment assignment. <h3>Results</h3> At week 8, 18.5% of patients in the ADA160/80 group (p=0.031 vs placebo) and 10.0% in the ADA80/40 group (p=0.833 vs placebo) were in remission, compared with 9.2% in the placebo group. Serious adverse events occurred in 7.6%, 3.8% and 4.0% of patients in the placebo, ADA80/40, and ADA160/80 groups, respectively. There were two malignancies in the placebo group, none in the ADA groups. There were no cases of tuberculosis and no deaths. <h3>Conclusions</h3> ADA160/80 was safe and effective for induction of clinical remission in patients with moderately to severely active ulcerative colitis failing treatment with corticosteroids and/or immunosuppressants. <h3>Clinical trial</h3> NCT00385736.
Recovery after open versus laparoscopic pyloromyotomy for pyloric stenosis: a double-blind multicentre randomised controlled trial
Authors: Nigel J Hall, Maurizio Pacilli, Simon Eaton, Kim Reblock, Barbara A Gaines, Aimee Pastor, Jacob C Langer, Antti I Koivusalo, Mikko P Pakarinen, Lutz Stroedter, Stefan Beyerlein, Munther Haddad, Simon Clarke, Henri Ford, Agostino Pierro
Journal: The Lancet (2009)
Prediction of Sensitivity of Rectal Cancer Cells in Response to Preoperative Radiotherapy by DNA Microarray Analysis of Gene Expression Profiles
Authors: Toshiaki Watanabe, Yasuhiro Komuro, Tomomichi Kiyomatsu, Takamitsu Kanazawa, Yoshihiro Kazama, Junichiro Tanaka, Toshiaki Tanaka, Yoko Yamamoto, Masatoshi Shirane, Tetsuichiro Muto, Hirokazu Nagawa
Journal: Cancer Research (2006)

Abstract Preoperative radiotherapy has been widely used to improve local control of disease and to improve survival in the treatment of rectal cancer. However, the response to radiotherapy differs among individual tumors. Our objective here was to identify a set of discriminating genes that can be used for characterization and prediction of response to radiotherapy in rectal cancer. Fifty-two rectal cancer patients who underwent preoperative radiotherapy were studied. Biopsy specimens were obtained from rectal cancer before preoperative radiotherapy. Response to radiotherapy was determined by histopathologic examination of surgically resected specimens and classified as responders or nonresponders. By determining gene expression profiles using human U95Av2 Gene Chip, we identified 33 novel discriminating genes of which the expression differed significantly between responders and nonresponders. Using this gene set, we were able to establish a new model to predict response to radiotherapy in rectal cancer with an accuracy of 82.4%. The list of discriminating genes included growth factor, apoptosis, cell proliferation, signal transduction, or cell adhesion–related genes. Among 33 discriminating genes, apoptosis inducers (lumican, thrombospondin 2, and galectin-1) showed higher expression in responders whereas apoptosis inhibitors (cyclophilin 40 and glutathione peroxidase) showed higher expression in nonresponders. The present study suggested the possibility that gene expression profiling may be useful in predicting response to radiotherapy to establish an individualized tailored therapy for rectal cancer. Global expression profiles of responders and nonresponders may provide insights into the development of novel therapeutic targets. (Cancer Res 2006; 66(7): 3370-4)
Phase I Study of C-TPF in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck
Authors: Robert I. Haddad, Roy B. Tishler, Charles Norris, Laura Goguen, Tracy A. Balboni, Rosemary Costello, Lori Wirth, Jochen Lorch, Britta Andreozzi, Donald Annino, Marshall R. Posner
Journal: Journal of Clinical Oncology (2009)

Phase I study to determine the maximum tolerated dose (MTD) of fluorouracil (FU) in the docetaxel/cisplatin/FU (TPF) regimen when combined with cetuximab (C) for induction treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN).Patients with previously untreated SCCHN were enrolled. FU cohorts were 700, 850, and 1,000 mg/m(2)/d for 4 days via continuous infusion. TPF given every 3 weeks for three cycles and C was given weekly for a total of 9 weeks, starting on day 1 of TPF. All patients received chemoradiotherapy after C-TPF.A total of 30 patients were enrolled and 28 were assessable. The median age was 57 years, 92% had stage 4 disease, 71% were oropharynx, and 100% had a performance status of 0. No dose-limiting toxicity (DLT) was encountered on dose levels 1 and 2. At dose level 3 of 1000 mg/m(2), one DLT was encountered and three more patients were enrolled with no DLTs. In the expansion cohort at the MTD, three DLT's were encountered. The decision was made to decrease the FU from 1,000 mg/m(2) to dose level 2 of 850 mg/m(2). A total of 13 patients were enrolled at the MTD of 850 mg/m(2). The number of average weeks that C was delivered was seven of nine planned.C-TPF appears to be safe and feasible as given in this study. GI toxicity (mucositis, enteritis, and diarrhea) appears to be the major combined DLT. Reducing the FU in TPF to 850 mg/m(2) reduces GI toxicity and is the recommended phase II dose.
Raymond Stewart Pine
Authors: Andrew Pine
Journal: BMJ (2004)

Former general practitioner Islington, London (b Portsmouth 1924; q St Bartholomew's Hospital, London, 1947), died from acute pancreatitis on 23 August 2004.​2004.




Figure 1




After national service Raymond became a general practitioner on the Isle of Wight. Two years later he took up practice in Hornsey Road, Islington, where he stayed until his retirement in 1984. He was a keen ornithologist, having recorded most species of the British Isles. He leaves a wife, Jane; three children; and two grandchildren.
Hyaluronectin in normal human skin and in basal cell carcinoma
Authors: ANNIE DELPECH, B. DELPECH, NICOLE GIRARD, MARIE CLAUDE BOULLIE, P. LAURET
Journal: British Journal of Dermatology (1982)

The localization of hyaluronectin has been studied in normal skin and in basal cell carcinoma. In fetal skin it is abundant in the dermis but absent from the epidermis, and in adult skin it is totally absent except in the hair sheaths and bulbs. In basal cell carcinoma it is abundant only in the stroma reaction. The presence of this protein in mesenchymatous tissues seems to be linked to zones of physiological or neoplastic proliferation.