tbuckley/cabot-search huggingface dataset:
Mental Health Bill for England and Wales may be postponed
Authors: Clare Dyer
Journal: BMJ (2006)

The government's controversial bill on mental health is expected to be shelved for this parliamentary session, amid widespread opposition from mental health professionals, fears about its effect on ethnic minority groups, and reported second thoughts in the Department for Constitutional Affairs.

The bill was due to be introduced before last Christmas but was held up while a racial impact assessment was carried out. A Department …
Human immunodeficiency virus (HIV)‐1 infects human hepatic stellate cells and promotes collagen I and monocyte chemoattractant protein‐1 expression
Authors: Ana C. Tuyama, Feng Hong, Yedidya Saiman, Chuansheng Wang, Derya Ozkok, Arevik Mosoian, Ping Chen, Benjamin K. Chen, Mary E. Klotman, Meena B. Bansal
Journal: Hepatology (2010)

Patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) develop more rapid fibrosis than those infected with HCV only. In HIV/HCV-coinfected patients, fibrosis progression correlates with HIV RNA levels, suggesting a direct role of HIV in liver fibrogenesis. Chemokine (C-C motif) receptor 5 (CCR5) and cysteine-X-cysteine receptor 4 (CXCR4), the two major coreceptors required for HIV entry into cells, are expressed on activated hepatic stellate cells (HSCs), the principle fibrogenic cell type in the liver. We therefore examined whether HIV can infect HSCs, explored the potential mechanisms of viral entry, and assessed the impact of infection as reflected by the ability of HSCs to transfer virus to T lymphocytes and elicit a proinflammatory and profibrogenic response. We report that the laboratory-adapted viruses HIV-IIIB (CXCR4-tropic or X4) and HIV-BaL (CCR5-tropic or R5) and primary HIV isolates can infect both a human stellate cell line, LX-2, and primary human HSCs. HIV entry and gene expression in HSCs was confirmed using HIV–green fluorescent protein (GFP) expression viral constructs in the presence or absence of the reverse-transcriptase inhibitor azidothymidine. CD4 expression on a subset of primary HSCs was demonstrated using fluorescence-activated cell sorting and immunofluorescence staining. Blocking experiments in the presence of anti-CD4, anti-CXCR4, and anti-CCR5 revealed that HIV entry into HSCs is predominantly CD4/chemokine coreceptor–independent. HIV infection promoted HSC collagen I expression and secretion of the proinflammatory cytokine monocyte chemoattractant protein-1. Furthermore, infected LX-2 cells were capable of transferring GFP-expressing virus to T lymphocytes in a coculture system. Conclusion: Taken together, our results suggest a potential role of HIV in liver fibrosis/inflammation mediated through effects on HSCs. The role of early highly active antiretroviral therapy initiation in patients with HIV/HCV coinfection warrants further investigation. (HEPATOLOGY 2010)
REPORT OF COMMITTEE ON LYE LEGISLATION TO THE SECTION ON LARYNGOLOGY, OTOLOGY AND RHINOLOGY
Authors: Chevalier Jackson
Journal: JAMA (1923)

Last year your committee submitted a report of a survey of the situation as to legislation providing for the labeling conspicuously with the word "poison" all retail packages of caustic alkalis on which survey a campaign for such legislation was to be based. We beg now to report that such a campaign was planned and carried out in Pennsylvania in support of House Bill No. 395, a copy of which is hereto attached. This bill was introduced by Dr. Benjamin Patterson, was passed by both branches of the legislature, was signed by Governor Pinchot, and has therefore become a law. Your committee acknowledges with gratitude the utmost courtesy and open-mindedness with which its communications were received and considered by Governor Pinchot and by the members of the legislature. The work of Hon. Benjamin Patterson is deserving of the highest commendation. Thanks for wise counsel and earnest support are due to
Positron Emission Tomography Measurement of Periodontal 18F-Fluorodeoxyglucose Uptake Is Associated With Histologically Determined Carotid Plaque Inflammation
Authors: Kenneth M. Fifer, Sadia Qadir, Sharath Subramanian, Jayanthi Vijayakumar, Amparo L. Figueroa, Quynh A. Truong, Udo Hoffman, Thomas J. Brady, Ahmed Tawakol
Journal: Journal of the American College of Cardiology (2011)
<i>PIK3CA</i> Mutation H1047R Is Associated with Response to PI3K/AKT/mTOR Signaling Pathway Inhibitors in Early-Phase Clinical Trials
Authors: Filip Janku, Jennifer J. Wheler, Aung Naing, Gerald S. Falchook, David S. Hong, Vanda M. Stepanek, Siqing Fu, Sarina A. Piha-Paul, J. Jack Lee, Rajyalakshmi Luthra, Apostolia M. Tsimberidou, Razelle Kurzrock
Journal: Cancer Research (2012)

PIK3CA mutations may predict response to PI3K/AKT/mTOR inhibitors in patients with advanced cancers, but the relevance of mutation subtype has not been investigated. Patients with diverse cancers referred to the Clinical Center for Targeted Therapy were analyzed for PIK3CA and, if possible, KRAS mutations. Patients with PIK3CA mutations were treated, whenever possible, with agents targeting the PI3K/AKT/mTOR pathway. Overall, 105 (10%) of 1,012 patients tested harbored PIK3CA mutations. Sixty-six (median 3 prior therapies) of the 105 PIK3CA-mutant patients, including 16 individuals (of 55 PIK3CA-mutant patients tested) with simultaneous KRAS mutations, were treated on a protocol that included a PI3K/AKT/mTOR pathway inhibitor; 17% (11/66) achieved a partial response (PR). Patients with a PIK3CA H1047R mutation compared with patients who had other PIK3CA mutations or patients with wild-type PIK3CA treated on the same protocols had a higher PR rate (6/16, 38% vs. 5/50; 10% vs. 23/174, 13%, respectively; all P ≤ 0.02). None of the 16 patients with coexisting PIK3CA and KRAS mutations in codon 12 or 13 attained a PR (0/16, 0%). Patients treated with combination therapy versus single-agent therapies had a higher PR rate (11/38, 29% vs. 0/28, 0%; P = 0.002). Multivariate analysis showed that H1047R was the only independent factor predicting response [OR 6.6, 95% confidence interval (CI), 1.02-43.0, P = 0.047). Our data suggest that interaction between PIK3CA mutation H1047R versus other aberrations and response to PI3K/AKT/mTOR axis inhibitors warrants further exploration.
Bronchogenic Cysts of the Mediastinum in Infancy
Authors: A. J. Eraklis, N. T. Griscom, J. B. McGovern
Journal: New England Journal of Medicine (1969)

Of 10 infants with mediastinal bronchogenic cysts seven were in severe or moderate respiratory distress at admission. In none was the precise diagnosis of bronchogenic cyst made before operation. In four, including all three fatal ones, the presence of a mediastinal mass was not even recognized. Seven of the eight infants operated upon survived and were alive and well up to 20 years later. Two infants died without surgery. Variable clinical and radiographic findings of bronchogenic cysts of the mediastinum may obscure diagnosis and delay treatment. Chest films may show severe hyperaeration, areas of collapse, atelectasis of an entire lung, or a mediastinal mass. Complete obstruction of a bronchus in utero can lead to retention of fetal fluid within the lung, which may be mistaken for a pulmonary tumor.
Genomic Medicine — A Primer
Authors: Alan E. Guttmacher, Francis S. Collins
Journal: New England Journal of Medicine (2002)

This review article launches our series on genomic medicine. It provides definitions of terms commonly used in genetics, delineates the distinction between genetics and genomics, and supplies examples of the ways in which genetic information can be used in the day-to-day care of patients. The mechanisms leading to the availability of more than 100,000 proteins from only approximately 30,000 genes are described. The various common types of mutations are identified and defined, and modes of inheritance — from simple mendelian to complex to mitochondrial — are detailed.
Certainly Not the First Neuroimaging Treatment Selection Biomarker
Authors: Theodore Henderson, Robert Tarzwell
Journal: JAMA Psychiatry (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Insulin Resistance, Impaired Early Insulin Response, and Insulin Propeptides as Predictors of the Development of Type 2 Diabetes
Authors: Björn Zethelius, C. Nicholas Hales, Hans O. Lithell, Christian Berne
Journal: Diabetes Care (2004)

OBJECTIVE—Defects in insulin secretion and insulin action are the major abnormalities in the development of type 2 diabetes. In middle-aged subjects, elevated plasma proinsulin has been found to predict type 2 diabetes. Therefore, our aim was to study the longitudinal relationships between baseline determinations of insulin sensitivity index (Si) assessed by euglycemic insulin clamp, the early insulin response (EIR) at an oral glucose tolerance test (OGTT), fasting intact proinsulin, 32–33 split proinsulin and specific insulin, and the development of type 2 diabetes in a population-based cohort of 70-year-old nondiabetic men (n = 667) with 7-year follow-up. RESEARCH DESIGN AND METHODS—A euglycemic insulin clamp study and a 75-g OGTT were performed at baseline, and fasting peptide concentrations were measured using specific two-site immunometric assays. Results from logistic regression models are presented as odds ratios (ORs) with 95% CIs for a 1-SD increase in the predictor variable. RESULTS—In separate multivariate analyses adjusted for EIR (OR 0.72, 95% CI 0.59–0.89) and Si (0.68, 0.58–0.88), 32–33 split proinsulin (1.49, 1.18–1.88) or intact proinsulin (1.30, 1.04–1.63) were significantly associated with the development of type 2 diabetes, whereas specific insulin (1.24, 0.91–1.66) was not. The significant associations between 32–33 split or intact proinsulin and the development of type 2 diabetes were unaltered after adjustment for BMI and glucose tolerance. CONCLUSIONS—Insulin propeptides predicted type 2 diabetes over a 7-year period in elderly men, independent of the EIR and Si.
HLA-matched allogeneic stem cell transplantation improves outcome of higher risk myelodysplastic syndrome A prospective study on behalf of SFGM-TC and GFM
Authors: M Robin, R Porcher, L Adès, E Raffoux, M Michallet, S François, J-Y Cahn, A Delmer, E Wattel, S Vigouroux, J-O Bay, J Cornillon, A Huynh, S Nguyen, M-T Rubio, L Vincent, N Maillard, A Charbonnier, R P de Latour, O Reman, H Dombret, P Fenaux, G Socié
Journal: Leukemia (2015)
Abnormal Excretion of Corticosteroid Sulphates in Patients with Breast Cancer
Authors: P. C. Ghosh, E. Lockwood, G. W. Pennington
Journal: BMJ (1973)

In a preliminary study, the 24-hour urinary excretion of corticosteroid sulphates and free cortisol have been measured in a group of patients with breast cancer and compared with the excretion of the same compounds in a group of normal women of similar age. Excretion of corticosteroid sulphates in the breast cancer group was found to be markedly raised. In a small number of patients with localized cancer of sites other than the breast the level of corticosteroid sulphate was not raised. If proved metastases were present a noticeable rise was observed.
Methimazole Toxicity from High Doses
Authors: James J. Wiberg, Frank Q. Nuttall
Journal: Annals of Internal Medicine (1972)

The toxic effects of high-dose methimazole therapy (120 mg/day) were studied in 25 consecutive patients receiving such therapy. Nine of the 25 patients had toxic reactions, 8 of which were severe. Rashes were most commonly seen, but two cases of agranulocytosis syndrome occurred. Although hyperthyroidism may be controlled more rapidly with high doses of this blocking agent, the observed morbidity suggests that such doses should not be used routinely.
Perspectives in the Treatment of Breast Cancer: 1976
Authors: ROBERT C. YOUNG
Journal: Annals of Internal Medicine (1977)

Breast cancer is the major cancer killer of women in the United States. Recent advances in therapy promise more effective control of this illness. The development of hormone receptor analysis permits us to better understand the mechanisms of action of steroid and peptide hormones and increases the likelihood of using there hormonal agents effectively. Prospective surgical and surgical adjuvant trials offer the opportunity to define accurately the appropriate surgical procedure and most effective postoperative therapy after initial surgery. The development of chemotherapy, first singly and now in combination, has led to improved treatment of patients with advanced disease and defined better chemotherapy for use in adjuvant settings. The investigation of a matrix of marker substances in breast cancer may uncover new methods to assess residual disease and to monitor disease recurrence.
Mercury in Fish
Authors: Thomas H. Jukes
Journal: JAMA (1975)

POLLUTION and contamination with mercury is an interesting and complex story, for in a toxicological sense there are "two mercurys." On the one hand, mercuric chloride and methylmercury are highly poisonous. Compounds of mercury, especially in fish and shellfish, have caused widely publicized incidents of poisoning in human beings. On the other hand, mercurous chloride was used as a laxative, and mercury and its compounds are employed in chemotherapy, in diuretics, and by dentists. All of the poisonings with mercury were tragic; some were caused by flagrant and inexcusable neglect by industry; others by illiteracy or even stupidity. The uproar over mercury in swordfish and canned tuna was unnecessary and somewhat ludicrous. The discovery of the protective effect of selenium was fascinating, and did much to clear the air. "All the rivers run into the sea, yet the sea is not full; unto the place from whence the rivers come,
The relationships of proteinuria, serum creatinine, glomerular filtration rate with cardiovascular disease mortality in Japanese general population
Authors: F. Irie, H. Iso, T. Sairenchi, N. Fukasawa, K. Yamagishi, S. Ikehara, M. Kanashiki, Y. Saito, H. Ota, T. Nose
Journal: Kidney International (2006)
Municipal solid wastes and their disposal.
Authors: R Stone
Journal: Environmental Health Perspectives (1978)

A brief overview is given of the sources, characteristics, and toxic constituents of municipal solid wastes. Several methods are presented for handling, treating, and disposal of solid wastes. Monitoring the landfill site is necessary; there has been a trend to recognize that municipal solid wastes may be hazardous and to provide separate secure handling, treatment, and disposal for their dangerous constituents. Under current state and Federal regulations, permits are being required to assure that proper handling of conventional solid wastes and more hazardous constituents are carefully managed.
ANAPHYLACTIC SHOCK WITH THE PARTIAL ANTIGEN OF THE TUBERCLE BACILLUS
Authors: John F. Enders
Journal: The Journal of Experimental Medicine (1929)

1. Typical lethal anaphylactic shock has been produced in guinea pigs by means of the specific carbohydrate derived from a human strain of tubercle bacillus. The phenomenon has been observed in animals both actively and passively sensitized. 2. Typical contractions have been evoked in the isolated uterus of guinea pigs upon the addition of the specific carbohydrate to the bath. 3. True anaphylactic shock against the specific carbohydrate in guinea pigs sensitized with the tubercle bacillus does not prevent or diminish the cutaneous reaction to O. T. in those animals which recover.
Testosterone and Androstenedione Blood Production Rates in Normal Women and Women with Idiopathic Hirsutism or Polycystic Ovaries*
Authors: C. Wayne Bardin, Mortimer B. Lipsett
Journal: Journal of Clinical Investigation (1967)

The average plasma testosterone concentration of women with either hirsutism or polycystic ovaries and hirsutism was higher (p < 0.01) than that of normal women although the ranges overlapped. Testosterone blood production rates averaged 830 +/- 120 SE and 1,180 +/- 310 SE mug per day in the two groups of hirsute women and 230 +/- 33 SE mug per day in normal women. The ranges did not overlap. The testosterone metabolic clearance rates of hirsute women (1,090 +/- 140 SE L per day) and of men (1,240 +/- 136 SE L per day) were significantly higher than those of normal women (590 +/- 44 SE L per day). These differences persisted when the metabolic clearance rates were corrected for surface area. We suggest that testosterone metabolic clearance rates vary directly with some function of testosterone production. The mean plasma androstenedione levels (2.8 +/- 0.35 SE and 2.8 +/- 0.30 SE mug per L) and production rates (6,060 +/- 450 SE and 7,360 +/- 345 SE mug per day) of the women with hirsutism or polycystic ovaries, respectively, were significantly higher than those of normal women (1.5 +/- 0.22 SE mug per L; 3,300 +/- 830 SE mug per day). The androstenedione metabolic clearance rates were the same in each group. Plasma androstenedione was the precursor of 49% of plasma testosterone in normal women and of 26% of plasma testosterone in hirsute women. Thus, 74% of the plasma testosterone in these subjects must have been either secreted or derived from a precursor that did not enter the plasma androstenedione pool.
Impact of Associated Conditions on Glycemic Control of NIDDM Patients
Authors: Eleuterio Ferrannini, Michael P Stern, Alfredo Quinones Galvan, Braxton D Mitchell, Steven M Haffner
Journal: Diabetes Care (1992)

To assess the impact of associated conditions (obesity, dyslipidemia, and hypertension) on the glycemic control of non-insulin-dependent diabetes mellitus (NIDDM) patients under home-life conditions.We analyzed the metabolic data of 271 NIDDM patients (89% Mexican American) screened in a population-based survey (the San Antonio Heart Study).Obesity was present in 77% of the patients, hypertension in 23%, hypertriglyceridemia (serum triglycerides greater than 2.9 mM) in 23%, and hypercholesterolemia (serum total cholesterol greater than 6.5 mM) in 14%. Forty percent of the patients had two or more comorbid conditions. With the use of a multiple linear regression model, which was adjusted for age, sex, ethnicity, distribution of body fat (waist-hip ratio), plasma insulin, and treatment (of both diabetes and hypertension), we found that the presence of higher serum triglyceride concentrations was associated with significantly higher plasma glucose levels both in the fasting state (1.4 mM, P less than 0.001) and 2 h after an oral glucose load (1.2 mM, P = 0.003). The presence of obesity, hypertension, or high serum cholesterol levels was not associated with significant changes in glycemic control. When the entire group was stratified by diabetes treatment (untreated n = 89, diet n = 75, oral agents n = 82, insulin n = 25) and after adjusting for age, sex, ethnicity, and waist-hip ratio, only fasting and 2-h plasma glucose and insulin concentrations were significantly different across treatment groups, with diet and oral agents being associated with higher fasting (P less than 0.001) and postglucose (P less than 0.005) plasma glucose levels and lower plasma insulin concentrations (P less than 0.005) compared with newly diagnosed patients. Neither serum lipids nor blood pressure differed across treatment.In NIDDM patients under home-life conditions, higher serum triglycerides are associated with higher fasting and postglucose hyperglycemia regardless of antidiabetic treatment. The presence of obesity, hypertension, or high serum cholesterol levels is not associated with significant changes in glycemic control.
Abstract 1642: Preclinical studies of MK-8745: Correlation between Aurora-A inhibitor sensitivity and Aurora-A activator
Authors: Aparajita Chowdhury, Ming Y. Tsai
Journal: Cancer Research (2010)

Abstract Selective small-molecule kinase inhibitors have emerged as an important class of anti-cancer agents, and have demonstrated encouraging clinical efficacy in several different malignancies. However, it has become clear that the clinical activity of these agents is typically limited to a subset of patients, indicating the need to develop a clear understanding of the various factors that influence clinical benefit. To date, most studies have identified cancer patients whose tumors have genetic alterations of the targeted kinase and have demonstrated their greatest clinical efficacy for the kinase inhibitors. However, recent drug discovery efforts are also being aimed at targeting kinases within oncogene-associated signaling pathways and the pathway-specific determinants of sensitivity. Aurora-kinase family members (Aurora kinases -A, B, C) have been implicated as key mitotic regulators essential for genomic stability. Aurora kinase A (AURKA) is highly expressed in multiple human cancers and has been shown to be a promising therapeutic target. In this study, we examined the effects of small molecule AURKA specific inhibitor MK-8745 on non-Hodgkin lymphoma (NHL) cells. Our results indicate that MK-8745 treatment leads to cell cycle arrest at G2/M phase with accumulation of tetraploid DNA followed by mitotic catastrophe and cell death in five cell lines (Granta 519, Jeko1, JVM2, Z138C and Akata). More importantly, we found that the sensitivity of the cell to the AURKA inhibitor is strongly correlated to the expression level of AURKA activators. We found that siRNA knockdown of one of the AURKA activators TPX2 increased MK-8745 sensitivity in drug resistant cell lines (Granta 519), whereas overexpression of TPX2 in MK-8745 sensitive cell (Z138C) lines increased drug resistance. This differential drug-sensitivity is specific to MK-8745 since treatment with pan-Aurora inhibitor (VE465, inhibitor of Aurora-A, B and C) and another mitotic drug, Taxol, did not show a differential sensitivity in these cell lines. The AURKA phosphorylation was decreased by MK-8745 treatment with simultaneous reduction in endogenous AURKA substrate TPX2, Eg5 and TACC3 protein levels. Our results suggest, beside p53, AURKA activators should be potential biomarkers for selecting subpopulations of patients for AURKA inhibitor treatment, while AURKA substrates can be the potential biomarkers for the effect of Aurora-A inhibitor treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1642.