tbuckley/cabot-search huggingface dataset:
Abstract 3869: Exploration of mechanisms for chromothripsis by irradiation
Authors: Maki Morishita, Tomoki Muramatsu, Shin Hayashi, Momoki Hirai, Yumiko Suto, Teruaki Konishi, Keiji Moriyama, Johji Inazawa
Journal: Cancer Research (2015)

Abstract Chromothripsis is the massive but highly localized chromosome rearrangements within a one-step catastrophic event rather than a series of subsequent and random alterations. Chromothripsis occurs commonly in various human cancers and it is thought to be associated with increasing malignancy and oncogenesis. However the causes and consequences of chromothripsis remain unclear. Therefore, to explore mechanisms of chromothripsis, we investigated whether chromothripsis was artificially induced by irradiation. We elicited DNA double-strand breaks in the oral cancer cell line HOC313, or its highly metastatic subline HOC313-LM by The Single Particle Irradiation system to Cell (SPICE), a focused vertical micro-beam system designed to irradiate the nuclei of adhesive cells. We established irradiated monoclonal sublines and analyzed the copy number variations (CNVs) and SNPs using SNP array. Chromosomal alterations, induced by irradiation including CNVs, were detected in some monoclonal sublines. Interestingly SNP array analysis showed that one subline named LM200-#25 had multiple chromosomal alterations which happened locally in chromosome 7. Moreover, we detected several chromosomal alterations such as t(12;7;11) translocation in LM200-#25 subline by Multi-Color FISH analysis. These results suggested that chromothripsis might be induced by irradiation in LM200-#25 subline. Citation Format: Maki Morishita, Tomoki Muramatsu, Shin Hayashi, Momoki Hirai, Yumiko Suto, Teruaki Konishi, Keiji Moriyama, Johji Inazawa. Exploration of mechanisms for chromothripsis by irradiation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3869. doi:10.1158/1538-7445.AM2015-3869
A Polycomb Repression Signature in Metastatic Prostate Cancer Predicts Cancer Outcome
Authors: Jindan Yu, Jianjun Yu, Daniel R. Rhodes, Scott A. Tomlins, Xuhong Cao, Guoan Chen, Rohit Mehra, Xiaoju Wang, Debashis Ghosh, Rajal B. Shah, Sooryanarayana Varambally, Kenneth J. Pienta, Arul M. Chinnaiyan
Journal: Cancer Research (2007)

Abstract The Polycomb Group (PcG) protein EZH2 is a critical component of a multiprotein complex that methylates Lys27 of histone 3 (H3K27), which consequently leads to the repression of target gene expression. We have previously reported that EZH2 is overexpressed in metastatic prostate cancer and is a marker of aggressive diseases in clinically localized solid tumors. However, the global set of genes directly regulated by PcG in tumors is largely unknown, and thus how PcG mediates tumor progression remains unclear. Herein we mapped genome-wide H3K27 methylation in aggressive, disseminated human prostate cancer tissues. Integrative analysis revealed that a significant subset of these genes are also targets of PcG in embryonic stem cells, and their repression in tumors is associated with poor prognosis. By stepwise cross-validation, we developed a “Polycomb repression signature” composed of 14 direct targets of PcG in metastatic tumors. Notably, solid tumor subtypes in which this gene signature is repressed show poor clinical outcome in multiple microarray data sets of tumors including breast and prostate cancer. Taken together, our results show a fingerprint of PcG-mediated transcriptional repression in metastatic prostate cancer that is reminiscent of stem cells and associated with cancer progression. Therefore, PcG proteins play a central role in the epigenetic silencing of target genes and functionally link stem cells, metastasis, and cancer survival. [Cancer Res 2007;67(22):10657–63]
ELECTRONARCOSIS—A THERAPY IN SCHIZOPHRENIA
Authors: ESTHER BOGEN TIETZ, GEORGE N. THOMPSON, A. VAN HARREVELD, C. A. G. WIERSMA
Journal: American Journal of Psychiatry (1945)

1. Electronarcosis is a safe and practical method of treatment for schizophrenia. Over 1000 treatments have been given without fatality or significant complications. 2. The therapeutic effects of electronarcosis in a group of schizophrenic patients were superior to those expected of electroshock treatment and about the same as results expected from insulin shock therapy.
Doxorubicin Affects Testicular Lipids with Long-Chain (C18-C22) and Very Long-Chain (C24-C32) Polyunsaturated Fatty Acids
Authors: Samanta R. Zanetti, Eduardo N. Maldonado, Marta I. Aveldaño
Journal: Cancer Research (2007)

Doxorubicin disrupts spermatogenesis by causing apoptosis of spermatogonia and primary spermatocytes. The aim of this study was to examine the effect of this agent on adult rat testicular lipids and their fatty acids. A single dose (7.5 mg/kg) and a multidose regime (3 mg/kg once a week for 4 weeks) were evaluated. Both treatments resulted in the gradual loss of spermatogenic cells and determined a marked reduction in testicular size and weight 9 weeks after their start. Germ cell loss was accompanied by a decrease in phospholipids, including glycerophospholipids and sphingomyelin. Concomitantly, glycerophospholipids lost selectively their major polyunsaturated fatty acid (PUFA), 22:5n-6, and sphingomyelin lost its major very long-chain PUFA (VLCPUFA), 28:4n-6 and 30:5n-6. The molecular species from which the lost polyenes originated were thus a trait of germ cells. A transient peak of 16:0-ceramide was observed 48 h after the single dose. In both doxorubicin regimes, sphingomyelin and ceramide with reduced amounts of VLCPUFA after about 4 weeks and with no VLCPUFA after 9 weeks resulted. By contrast, triglycerides and especially cholesterol esters (CE) tended to accumulate in the testes undergoing germ cell death, probably in the surviving Sertoli cells, their fatty acid patterns suggesting that initially, these lipids retained part of the PUFA coming from, or no longer used for, the synthesis of germ cell glycerophospholipids. As the latter decreased, CE accumulated massively 9 weeks after starting doxorubicin treatment, 20:4n-6 becoming their major PUFA. Part of these CEs may derive from surviving steroidogenic cells.
NHS prescription charges work against aims of new white paper
Authors: Adrian O'Dowd
Journal: BMJ (2006)

The current prescription charging system could seriously undermine the aims of the government's new white paper to make healthcare services more accessible to people who need them most, MPs heard last week.

The charges are likely to hinder attempts to make the health service better at helping groups of people who currently find it difficult to get the right health care, such as people in underserved deprived areas, witnesses told the health select committee as part of its continuing inquiry into NHS charges.

Witnesses were asked how the present system of prescription charges affected the policy set out in the …
Anticitrullinated protein/peptide antibody assays in early rheumatoid arthritis for predicting five year radiographic damage
Authors: O Meyer
Journal: Annals of the Rheumatic Diseases (2003)

To study the value of antibodies to citrullinated proteins/peptides for predicting joint outcomes in patients with recent onset rheumatoid arthritis (RA).191 patients with RA onset within the past year were followed up prospectively for five years. Serum samples obtained from 145 patients at baseline before disease modifying antirheumatic drug treatment were examined using three anticitrullinated protein/peptide antibody assays: antiperinuclear factor (APF) by indirect immunofluorescence (IIF), antikeratin antibodies (AKA) by IIF, and anti-cyclic citrullinated peptide (CCP) antibodies by enzyme linked immunosorbent assay (ELISA). Radiographs of the hands and feet taken at baseline and after three and five years were evaluated using Sharp scores modified by van der Heijde.Anti-CCP ELISA was positive in 58.9% of patients. APF/anti-CCP agreement was 77%. The likelihood of a total Sharp score increase after five years was significantly greater among patients with anti-CCP antibodies (67%; odds ratio (OR) 2.5; 95% confidence interval (95% CI) 1.2 to 5.0) or APF (57%; OR 2.4; 95% CI 1.2 to 4.9) but not rheumatoid factor (RF; OR 0.7; 95% CI 0.3 to 1.5). Mean values for radiographic damage, erosion, and joint narrowing scores at the three times were significantly higher in patients with anti-CCP or APF than in those without. AKA did not significantly predict radiographic damage. In separate analyses of patients with and without RF, anti-CCP or APF was better than RF for predicting total joint damage and joint damage progression after five years.Antibodies to citrullinated proteins/peptides determined early in the course of RA by APF IIF or anti-CCP ELISA are good predictors of radiographic joint damage. Further studies of clinical, laboratory, and genetic parameters are needed to improve RA outcome prediction in clinical practice.
Atrial Septal Defect: Factors Affecting the Surgical Mortality Rate
Authors: DWIGHT C. MCGOON, H. J. C. SWAN, ROBERT O. BRANDENBURG, DANIEL C. CONNOLLY, JOHN W. KIRKLIN
Journal: Circulation (1959)

Analysis of accumulated experience with the repair of atrial septal defect in 119 adults has revealed several factors determinable preoperatively that appear to have a strong influence on the operative risk. These factors are related to the presence of pulmonary vascular disease or heart failure and contribute importantly to the selection of patients for operation.
IL-25 regulates Th17 function in autoimmune inflammation
Authors: Melanie A. Kleinschek, Alexander M. Owyang, Barbara Joyce-Shaikh, Claire L. Langrish, Yi Chen, Daniel M. Gorman, Wendy M. Blumenschein, Terrill McClanahan, Frank Brombacher, Stephen D. Hurst, Robert A. Kastelein, Daniel J. Cua
Journal: The Journal of Experimental Medicine (2007)

Interleukin (IL)-25 is a member of the IL-17 family of cytokines. However, unlike the other members of this family, IL-25 promotes T helper (Th) 2 responses. We now show that IL-25 also regulates the development of autoimmune inflammation mediated by IL-17-producing T cells. We have generated IL-25-deficient (il25-/-) mice and found that they are highly susceptible to experimental autoimmune encephalomyelitis (EAE). The accelerated disease in the il25-/- mice is associated with an increase of IL-23 in the periphery and a subsequent increase in the number of inflammatory IL-17-, IFNgamma-, and TNF-producing T cells that invade the central nervous system. Neutralization of IL-17 but not IFNgamma in il25-/- mice prevented EAE, suggesting that IL-17 is a major disease-promoting factor. IL-25 treatment at several time points during a relapse-remitting model or chronic model of EAE completely suppressed disease. IL-25 treatment induced elevated production of IL-13, which is required for suppression of Th17 responses by direct inhibition of IL-23, IL-1beta, and IL-6 expression in activated dendritic cells. Thus, IL-25 and IL-17, being members of the same cytokine family, play opposing roles in the pathogenesis of organ-specific autoimmunity.
Natriuretic Effect of Angiotensin in Dogs Revealed after Administration of Reserpine and Guanethidine
Authors: JOHN C. MCGIFF
Journal: Circulation Research (1967)

In untreated dogs anesthetized with morphine-chloralose, a small dose of angiotensin (0.0375 µg/kg per min) produced a large reduction in renal blood flow, a smaller reduction in glomerular filtration rate and an antinatriuresis. A graded change in the excretion of sodium in response to angiotensin occurred after the successive administration of reserpine and guanethidine. In reserpinetreated dogs, angiotensin did not produce an antinatriuresis, whereas in the same dogs after giving guanethidine, a natriuresis occurred in response to angiotensin (from a control of 60 to 189 µEq Na/min). The effects of angiotensin on blood pressure and glomerular filtration rate were similar in all dogs. The renal vasoconstrictor effect of angiotensin was decreased in 3 of 8 dogs after guanethidine. At the high dose of angiotensin (0.375 µg/kg per min), the natriuresis was larger (from a control of 75 to 353 µEq Na/min) and was unrelated to changes in glomerular filtration rate or renal blood flow. In reserpine- and guanethidine-treated dogs, angiotensin increased sodium excretion sufficiently during renal arterial constriction to produce a large reduction in renal blood flow and the filtered load of sodium. These results suggest that angiotensin has a renal tubular action that is uncovered by sympathetic blockade produced by reserpine and guanethidine.
Physiological characteristics of top level off-road motorcyclists
Authors: A W Gobbi, R A Francisco, B Tuy, R S Kvitne
Journal: British Journal of Sports Medicine (2005)

The study aims to analyse the physiological characteristics of top level off-road motocross, enduro, and desert rally motorcyclists to facilitate the design of a specific training program.Twenty seven off-road top level riders participated in this study which measured anthropometric data, maximum aerobic power with incremental tests of both arms and legs, isokinetic dynamometry of the knee and elbow, handgrip strength, heart rate, and blood lactate concentrations during competition.The physical demands of the various races appear to influence the development of distinct musculoskeletal characteristics, as well as aerobic and anaerobic metabolism. Motocross riders have more muscle mass, higher isokinetic handgrip strength, and greater aerobic power than enduro and desert rally riders. However, there are no significant anthropometric and physiological differences between desert rally and enduro riders. Desert rally riders tend to be overweight with maximum aerobic power similar to that of healthy individuals. The mechanical characteristics of the motorcycle and the technical and tactical skills of the riders seem to be more important for race success than the metabolic capabilities of the rider.Desert rally and enduro riders present similar anthropometric and physiological characteristics. Both have a maximum aerobic power similar to that of healthy normal individuals, although desert rally riders tend to be overweight. Motocross riders on the other hand, have more muscle mass, more strength, and greater aerobic power. The differences observed suggest the need for a specific training program to address the requirements of different riders to reduce the possibility of injury.
Angiogenic Switch of Angiopietins-Tie2 System and Its Prognostic Value in Bladder Cancer
Authors: Tibor Szarvas, Tobias Jäger, Martin Tötsch, Frank Vom Dorp, Carsten Kempkensteffen, Ilona Kovalszky, Imre Romics, Süleyman Ergün, Herbert Rübben
Journal: Clinical Cancer Research (2008)

Vascular endothelial growth factor (VEGF), angiopoietins (Ang-1 and Ang-2), and their receptor Tie2 are critically involved in both normal and pathologic angiogenesis. The aim of this study was to explore the role of Ang-1, Ang-2, VEGF, and Tie2 in the development and progression of bladder cancer as well as to examine their prognostic value in this tumor type.Tumor samples of 113 bladder cancer patients, normal bladder epithelium of 5 noncancer patients, and two low-grade (UMUC3 and RT4) and two high-grade (J82 and T24) bladder cancer cell lines were analyzed by quantitative real-time PCR. The expression data were analyzed performing Wilcoxon rank-sum and Kaplan-Meier log-rank tests as well as univariate Cox analyses and Cox proportional hazards regression model.In tissues of noninvasive bladder tumors, Ang-1 expression was significantly lower (P < 0.001), whereas VEGF expression was significantly higher (P = 0.031) than in normal bladder tissue. These findings were also confirmed at the protein level by immunohistochemistry. In contrast, Tie2 and Ang-2 abundance in tumor did not differ significantly from that in normal bladder tissue. Multivariate analysis identified Ang-2 as a strong and independent predictor of tumor recurrence [hazard ratio (HR), 10.18; 95% confidence interval (95% CI), 2.69-38.49; P < 0.001] and Tie2 expression as an independent favorable prognostic factor for both metastasis (HR, 0.31; 95% CI, 0.11-0.89; P = 0.029) and disease-specific survival (HR, 0.25; 95% CI, 0.10-0.62; P = 0.003).These data show the strongest change in expression of VEGF and Ang-1 in superficial bladder cancer in comparison with normal bladder epithelium and the invasive tumor stages. The prognostic significance of Ang-2 and Tie2 underlines the essential role of angiopoietins-Tie2 system in progression of bladder cancer.
Diabetic Nephropathy and Proliferative Retinopathy with Normal Glucose Tolerance
Authors: J Y C Chan, E Cole, A K Hanna
Journal: Diabetes Care (1985)

A 61-yr-old man presented with the nephrotic syndrome and normal oral glucose tolerance. Renal biopsy showed the nodular (Kimmelstiel-Wilson) and diffuse glomerulosclerosis lesions characteristic of diabetes. Direct ophthalmoscopy and fluorescein angiography demonstrated a picture of advanced proliferative diabetic retinopathy. The patient had no history of diabetes mellitus and upon testing had normal glucose values in response to an oral glucose tolerance test. Insulin response to an intravenous glucose tolerance test was abnormally low. It is concluded that the nodular glomerulosclerosis lesions and proliferative retinopathy, thought to be specific for diabetes mellitus, may present in the absence of either overt clinical diabetes or impaired glucose tolerance.
Poor Survival for US Pacific Islander Cancer Patients: Evidence From the Surveillance, Epidemiology, and End Results Database: 1991 to 2004
Authors: William B. Goggins, Grace K.C. Wong
Journal: Journal of Clinical Oncology (2007)

Purpose Although racial and ethnic differences in cancer survival in the United States have been studied extensively, little is known about cancer survival in US Pacific Islanders (PIs), a fast-growing and economically disadvantaged minority group. Methods Using data from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registries, we compared cause-specific and all-cause survival for female breast, prostate, lung, colorectal, stomach and liver cancer for Native Hawaiians, Samoans, other PIs (including Tongans, Guamanians, and others), African Americans, and Native Americans with non-Hispanic whites using Cox proportional hazards models. Separate models were fitted adjusting for demographic factors only and demographic and disease severity variables. Results Among all groups, Samoans were the most likely to present with advanced disease and had the worst cause-specific survival for all sites considered. Samoans had particularly poor results (adjusted for demographic variables only) for female breast (relative risk [RR] = 3.05; 95% CI, 2.31 to 4.02), colorectal (RR = 1.82; 95% CI, 1.37 to 2.41) and prostate (RR = 4.82; 95% CI, 3.38 to 6.88) cancers. Native Hawaiians and other PIs also had significantly worse cause-specific survival than did non-Hispanic whites for most sites, but generally had better survival than African Americans or Native Americans. Conclusion Much of the survival disadvantage for PI groups appears to be a result of late diagnosis, and thus targeted interventions have much potential to reduce cancer mortality in this group. More research is needed to find explanations for the particularly poor cancer survival for Samoans in the United States.
The Effect of Magnesium Supplementation in Increasing Doses on the Control of Type 2 Diabetes
Authors: Maria de Lourdes Lima, Thomaz Cruz, Judith Carreiro Pousada, Luiz Erlon Rodrigues, Karyne Barbosa, Valquiria Canguçu
Journal: Diabetes Care (1998)

OBJECTIVE Hypomagnesemia occurs in 25–38% of patients with type 2 diabetes. Several studies have suggested an association between magnesium (Mg) depletion and insulin resistance and/or reduction of insulin secretion in these cases. Our purpose was to evaluate if Mg supplementation (as magnesium oxide [MgO]) would improve metabolic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS We studied 128 patients with type 2 diabetes (32 men, 96 women, aged 30–69 years), treated by diet or diet plus oral antidiabetic drugs, in the Bahia Federal University Hospital, Brazil. Patients at risk for hypomagnesemia or with reduced renal function were excluded. This study was a clinical randomized double-blind placebo-controlled trial. Patients received either placebo, 20.7 mmol MgO, or 41.4 mmol MgO daily(elementary Mg) for 30 days. Mg concentrations were measured in plasma, in mononuclear cells, and in 24-h urine samples. Fasting blood glucose, HbA1, and fructosamine were used as parameters of metabolic control. RESULTS Of the patients, 47.7% had low plasma Mg, and 31.1% had low intramononuclear Mg levels. Intracellular Mg in patients with diabetes was significantly lower than in the normal population (62 blood donors; 1.4 ± 0.6 vs. 1.7 ± 0.6 μg/mg of total proteins). No correlation was found between plasma and intracellular Mg concentrations (r = −0.179; P = 0.15) or between Mg concentrations and glycemic control (r = −0.165; P = 0.12). Intracellular Mg levels were lower in patients with peripheral neuropathy than in those without (1.2 ± 0.5 vs. 1.5 ± 0.6 μg/mg). Similar findings were observed in patients with coronary disease (1.0 ± 0.5 vs. 1.5 ± 0.6 μg/mg). In the placebo and in the 20.7 mmol Mg groups, neither a change in plasma and intracellular levels nor an improvement in glycemic control were observed. Replacement with 41.4 mmol Mg tended to increase plasma, cellular, and urine Mg and caused a significant fall (4.1 ± 0.8 to 3.8 ± 0.7 mmol/1) in fructosamine (normal, 1.87–2.87 mmol/1). CONCLUSIONS Mg depletion is common in poorly controlled patientswith type 2 diabetes, especially in those with neuropathy or coronary disease. More prolonged use of Mg in doses that are higher than usual is needed toestablish its routine or selective administration in patients with type 2 diabetes to improve control or prevent chronic complications.
A RESEARCH MODEL FOR THE EVALUATION OF THE EFECT OF PSYCHOPHARMACOLOGICAL AGENTS
Authors: DAVID W. MCCREIGHT, NOLAN D. C. LEWIS, MORRIS REBY, JOSEPH M. TOBIN
Journal: American Journal of Psychiatry (1961)

Our results indicate that minimal results were obtained from the use of this drug in our study of 47 patients. The study has also indicated that the design and methodology used in this research provided an acceptable basis for collaboration between a central Bureau of Research and a state hospital staff.