tbuckley/cabot-search huggingface dataset:
Risk Factors for the Development of Type II Diabetes Among Men Enrolled in the Usual Care Group of the Multiple Risk Factor Intervention Trial
Authors: B Jessica Shaten, George Davey Smith, Lewis H Kuller, James D Neaton
Journal: Diabetes Care (1993)

OBJECTIVE To study the association between selected risk factors and the subsequent incidence of type II diabetes over a 5-yr period. RESEACH DESIGN AND METHODS Between 1973 and 1976, a cohort of men from 22 clinical centers throughout the U.S. enrolled in the Usual Care group of the Multiple Risk Factor Intervention Trial. The men (5420 white, 428 black, 56 Asian, 70 Hispanic, and 26 other) were nondiabetic at baseline, were in the upper 15% of risk for coronary heart disease, and had at least two annual follow-up visits for fasting glucose measurements. The average age was 46 yr and average body mass index was 27.6 kg/m . Incidence of diabetes was defined as use of insulin or hypoglycemic agents, fasting glucose ≥140 mg/dl on two consecutive annual visits, or fasting glucose ≥ 140 mg/dl followed the next year by insulin or hypoglycemic use. Observations were taken annually over a 5-yr period. RESULTS Cumulative incidence of diabetes over 5 yr was 4.1%, with 247 incident cases. Development of diabetes was directly associated with race (blacks higher than non-blacks), reported parental history of diabetes, and with baseline levels of body mass index, fasting glucose, and glucose 1 h after a 75-g oral glucose load. These associations were statistically significant in both univariate and multivariate models. A significant interaction was observed between race and reported parental history of diabetes in development of diabetes, particularly within black men who reported a parental history. These individuals had higher than expected rates of diabetes development. CONCLUSIONS The data from men in the Usual Care group enrolled in the Multiple Risk Factor Intervention Trial confirm previous findings regarding the associations between the development of diabetes and baseline glucose levels, obesity, race, and parental history of diabetes. The identification of these risk factors provides very powerful tools to identify individuals at high risk of diabetes mellitus who may be amenable to intervention, thereby reducing their risk of developing the disease and its complications.
Abstract 4463: Activation of FGFR signaling as a mechanism of acquired resistance to erlotinib in EGFR-mutant lung cancer associated with an EMT.
Authors: Xiaofen Ye, Peng Yue, Rajesh Patel, Zora Modrusan, Jeff Settleman, Avi Ashkenazi, Robert L. Yauch
Journal: Cancer Research (2013)

Abstract Treatment of NSCLC patients harboring activating EGFR mutations with EGFR TKIs results in anti-tumor responses to therapy, however patients ultimately progress on therapy due to the acquisition of drug resistance. Known mechanisms of resistance include secondary mutations in the EGFR gene (EGFRT790M) or MET gene amplification, however the underlying mechanism of resistance remains to be elucidated in ∼40-45% of cases. Previous studies provide evidence for an epithelial-to-mesenchymal transition (EMT) in a subset of cases that is not associated with the known mechanisms of resistance. In this study, we identify 2 models of acquired resistance to erlotinib that are associated with an EMT phenotype and a dependence on autocrine FGF-FGFR signaling for resistance. Evidence for FGFR pathway activation in the erlotinib-resistant cell population included an increase in FGF2, FGFR1 and phospho-FRS2. Inhibition of FGFR signaling using a small molecule kinase inhibitor or FGFR1-Fc neutralization of FGFR1 ligands re-sensitized resistant cells to erlotinib. Re-sensitization was accompanied by an inhibition of downstream signaling. In contrast, inhibition of AXL, a kinase that has recently been identified as an EMT-associated driver of erlotinib resistance in some pre-clinical models, failed to re-sensitize erlotinib-resistant cells. Our findings are consistent with autocrine FGFR pathway activation, as FGF ligand neutralization in the absence of an exogenous source of ligand can re-sensitize cells to erlotinib. Finally, FGFR pathway inhibition suppressed the development of resistance to erlotinib in sensitive parental cells. These data indicate that FGFR activation could potentially serve as a mechanism of acquired resistance to erlotinib in cases associated with an EMT and suggest that combined inhibition of EGFR and FGFR signaling could be beneficial in treating such cases. Citation Format: Xiaofen Ye, Peng Yue, Rajesh Patel, Zora Modrusan, Jeff Settleman, Avi Ashkenazi, Robert L. Yauch. Activation of FGFR signaling as a mechanism of acquired resistance to erlotinib in EGFR-mutant lung cancer associated with an EMT. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4463. doi:10.1158/1538-7445.AM2013-4463
Prospective assessment of donor blood screening for antibody to hepatitis C virus by first- and second-generation assays as a means of preventing posttransfusion hepatitis
Authors: S Takano, K Nakamura, S Kawai, O Yokosuka, Y Satomura, M Omata
Journal: Hepatology (1996)

In November 1989, the Japanese Red Cross began screening blood donors for the hepatitis C virus antibody (anti-HCV) by first-generation assay and high-titer hepatitis B virus core antigen antibody. A significant reduction in the incidence of acute posttransfusion hepatitis was reported; however, the incidence still ranged from 2% to 4%. The Red Cross changed to the second-generation assay in February 1992, the objective being the complete elimination of potential posttransfusion hepatitis. The aim was to elucidate the advantage of second-generation assay as a blood-donor screening test. The incidence of posttransfusion hepatitis after the introduction of second-generation assay was compared with that before the introduction of the first-generation assay and with that during its use. The incidence of posttransfusion hepatitis was 9.6% (216/2,240) before anti-HCV-s donor screening. It was 3.7% (24/655) and 0.9% (3/326) after the introductions of the first-and second-generation hepatitis C virus (HCV) assays, respectively (χ 2 = 50.0, P &lt; .01). Blood-donor screening by second-generation anti-HCV provided a significant benefit compared with the first-generation assay.
Prognostic Significance of Left Anterior Hemiblock in Patients With Suspected Coronary Artery Disease
Authors: Elena Biagini, Abdou Elhendy, Arend F.L. Schinkel, Stefan Nelwan, Vittoria Rizzello, Ron T. van Domburg, Claudio Rapezzi, Guido Rocchi, Maarten L. Simoons, Jeroen J. Bax, Don Poldermans
Journal: Journal of the American College of Cardiology (2005)
Abstract LB-80: Exome sequencing of murine p53-knockout T-cell lymphomas reveals Pten loss and Cdk6 amplification as key steps toward cellular transformation
Authors: Crissy Dudgeon, Chang Chan, Yvonne Sun, Arnold J. Levine
Journal: Cancer Research (2014)

Abstract Loss of the tumor suppressor, p53, occurs in over 50% of cancers. The ability for p53 to protect the cell from tumorigenesis is based on its ability to induce cell cycle arrest, apoptosis, and senescence following genotoxic stress. Furthermore, genetic deletion of p53 in mice gives rise to spontaneous thymic (T-cell) lymphomas and sarcomas. In this study, we used the p53-knockout (KO) mouse as a model for progression of tumorigenesis. We first analyzed genomic DNA of p53-KO and WT normal thymus at various ages and p53-KO thymic lymphomas using TCRβ sequencing, allowing us to determine the clonality of the T cell repertoire. These data suggest that p53-KO thymic lymphomas were mostly oligoclonal, with some tumors comprising of a dominant clone. We further analyzed tumors with dominant clones for genomic instability by exome sequencing. Sequencing analysis revealed that there were many non-synonymous mutations occurring in each tumor, but with no similarities between tumors. On the other hand, all of the murine tumors had deletion of Pten and amplification of Cdk6. This is in stark contrast to what is seen in most human T cell lymphoblastic leukemias, which have activating mutations in Notch1 and loss of Arf. Interestingly, loss of Pten not only occurred in all tumors, but also in most, if not all, clones in the tumor. This suggests that Pten loss is an early event driving T cell transformation in a p53-KO background. Using this data, we found the somatic mutation rate in the tumors to be 1000-fold greater than the germline mutation rate. Loss of p53 also caused chromosomal abnormalities as seen with increased copy number variations. Taken together, our work suggests that, with initial loss of p53, the path to T cell tumorigenesis is vastly different from that of human tumors. Without p53, the somatic genome increases in mutation rate and copy number variations, thus solidifying p53's role as guardian of the genome. Citation Format: Crissy Dudgeon, Chang Chan, Yvonne Sun, Arnold J. Levine. Exome sequencing of murine p53-knockout T-cell lymphomas reveals Pten loss and Cdk6 amplification as key steps toward cellular transformation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-80. doi:10.1158/1538-7445.AM2014-LB-80
Subthreshold Hypomanic Symptoms in Progression From Unipolar Major Depression to Bipolar Disorder
Authors: Jess G. Fiedorowicz, Jean Endicott, Andrew C. Leon, David A. Solomon, Martin B. Keller, William H. Coryell
Journal: American Journal of Psychiatry (2010)

Objective: The authors assessed whether subthreshold hypomanic symptoms in patients with major depression predicted new-onset mania or hypomania. Method: The authors identified 550 individuals followed for at least 1 year in the National Institute of Mental Health Collaborative Depression Study with a diagnosis of major depression at intake. All participants were screened at baseline for five manic symptoms: elevated mood, decreased need for sleep, unusually high energy, increased goal-directed activity, and grandiosity. Participants were followed prospectively for a mean of 17.5 years and up to 31 years. The Longitudinal Interval Follow-up Examination was used to monitor course of illness and to identify any hypomania or mania. The association of subthreshold hypomanic symptoms at baseline with subsequent hypomania or mania was determined in survival analyses using Cox proportional hazards regression. Results: With a cumulative probability of one in four on survival analysis, 19.6% (N=108) of the sample experienced hypomania or mania, resulting in revision of diagnoses for 12.2% to bipolar II disorder and 7.5% to bipolar I disorder. Number of subthreshold hypomanic symptoms, presence of psychosis, and age at illness onset predicted progression to bipolar disorder. Decreased need for sleep, unusually high energy, and increased goal-directed activity were specifically implicated. Conclusions: Symptoms of hypomania, even when of low intensity, were frequently associated with subsequent progression to bipolar disorder, although the majority of patients who converted did not have any symptoms of hypomania at baseline. These results suggest that continued monitoring for the possibility of progression to bipolar disorder is necessary over the long-term course of major depressive disorder.
Book Review Non-Hodgkin's Lymphomas Edited by Peter M. Mauch, James O. Armitage, Bertrand Coiffier, Riccardo Dalla-Favera, and Nancy Lee Harris. Philadelphia, Lippincott Williams &amp; Wilkins, 2004. $189. 0-7817-3526-2
Authors: Bruce D. Cheson
Journal: New England Journal of Medicine (2004)
Rifaximin, gut microbes and mucosal inflammation: unraveling a complex relationship
Authors: Jun Gao, Merritt Gillilland, Chung Owyang
Journal: Gut Microbes (2014)

Rifaximin is a non-systemic, broad-spectrum antibiotic that acts against gram-positive, gram-negative, and anaerobic bacteria. Clinical studies indicate that rifaximin is beneficial in treating irritable bowel syndrome (IBS). The mechanism responsible for the beneficial effects of rifaximin is not clear. In a recent study, we reported that rifaximin alters the bacterial population in the ileum of rats, leading to a relative abundance of Lactobacillus species. These changes prevent gut inflammation and visceral hyperalgesia caused by chronic stress. To more closely mirror human clinical studies in which rifaximin is used to treat IBS symptoms, we performed additional studies and showed that rifaximin reversed mucosal inflammation and barrier dysfunction evoked by chronic stress. These beneficial effects were accompanied by a striking increase in the abundance of Lactobacillaceae and a marked reduction in the number of segmented filamentous bacteria after rifaximin treatment. These microbial changes may contribute to the antiinflammatory effects of rifaximin on the intestinal mucosa.
A comparatively inexpensive implantable miniature pressure transducer
Authors: G. C. V. D. BOS, J. DOLFING, F. NASSENSTEIN, B. HEEROOMS, R. BUITENWEG, W. ENGEL, F. K. DIJKEMA
Journal: Cardiovascular Research (1974)

An implantable pressure transducer has been constructed from a pressure sensitive transistor. The electronic as well as the mechanical construction are outlined together with the construction of the implantable skin button.
BIRTH CONTROL AND CONTRACEPTION
Authors: Haven Emerson
Journal: JAMA (1934)

To the Editor:—   editorial on Birth Control and Contraception inThe Journal, September 8, is naturally of interest to the National Committee on Maternal Health, which since 1923 has been studying these and allied questions as problems of public health and the practice of medicine. Since 1929 we have conducted a systematic and comprehensive investigation into the nature and merits of various contraceptive products and methods.  result of the first three years study, done in cooperation with the University of Edinburgh, was published in a volume by Cecil I. B. Voge, Ph.D., F.R.S.E., F.R.S.M., under the title of The Chemistry and Physics of Contraceptives (London, Jonathan Cape, 1933).  Voge's study established the factual basis for the evaluation of contraceptives in terms of physics, chemistry and biology.  next step was obviously to apply the tests to the commercial products now most widely used and exploited, and concomitantly the
Quantification of Extracellular and Intracellular Adenosine Production
Authors: Andreas Deussen, Margit Stappert, Stefan Schäfer, Malte Kelm
Journal: Circulation (1999)

Background —Inhibitors of adenosine membrane transport cause vasodilation and enhance the plasma adenosine concentration. However, it is unclear why the plasma adenosine concentration rises rather than falls when membrane transport is inhibited. We tested the hypothesis that the cytosolic adenosine concentration exceeds the interstitial concentration under well-oxygenated conditions. Methods and Results —In isolated, isovolumically working guinea pig hearts (n=50), the release rate of adenosine and accumulation of S -adenosylhomocysteine (after 20 minutes of 200 μmol/L homocysteine), a measure of the free cytosolic adenosine concentration, were determined in the absence and presence of specific and powerful blockers of adenosine membrane transport (nitrobenzylthioinosine 1 μmol/L), adenosine deaminase (erythro-9-hydroxy-nonyl-adenine 5 μmol/L), and adenosine kinase (iodotubericidine 10 μmol/L). Data analysis with a distributed multicompartment model revealed a total cardiac adenosine production rate of 2294 pmol · min −1 · g −1 , of which 8% was produced in the extracellular region. Because of a high rate of intracellular metabolism, however, 70.3% of extracellularly produced adenosine was taken up into cellular regions, an effect that was effectively eliminated by membrane transport block. The resulting ≈2.8-fold increase of the interstitial adenosine concentration evoked near-maximal coronary dilation. Conclusions —We rejected the hypothesis that the cytosolic adenosine concentration exceeds the interstitial. Rather, there is significant extracellular production, and the parenchymal cell represents a sink, not a source, for adenosine under well-oxygenated conditions.
Gland Extracts in Experimental Carcinoma and Sarcoma of Albino Rats
Authors: O. M. GRUHZIT
Journal: Annals of Internal Medicine (1931)

Article1 June 1931Gland Extracts in Experimental Carcinoma and Sarcoma of Albino RatsO. M. GRUHZIT, M. D.O. M. GRUHZIT, M. D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-4-12-1589 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptRecent publications directed to the possible beneficial effect of organ extracts in cancer, have led us to evaluate a number of these extracts in experimental carcinoma and sarcoma of rats.EXPERIMENTALA series of albino rats were inoculated with the Flexner-Jobling carcinoma* or Jensen sarcoma* of rats. When the tumor reached in size about one square centimeter, the animals were divided into three groups and placed under treatment. One group was treated with the hormone extract; the second group remained as untreated controls and the third group was placed on treatment with an extract of oxen testis prepared in a...Bibliography1 COFFEYHUMBER WBLD: Extract of Adrenal Cortex Substance. California and Western Medicine 33: 640, 1930. MedlineGoogle Scholar2 HANSON AM: Treatment of Cancer with Thymus Extract. J.A.M.A. 94:652, 1930. CrossrefGoogle Scholar3 BISHOFFMAXWELL FLC: Hormones in Cancer. Jour. Pharm. and Exp. Therapy 40: 97, 1930. Google Scholar4 ITAMIMCDONALD SE: Adrenal Cortex Extracts and Cancer. Science 72 (no. 1870) : 460, 1930. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Research and Biological Laboratories Parke, Davis and Company Detroit, Michigan*Original tumor bearing rats were obtained from Dr. F. C. Wood and the U. S. National Institute of Health.**U. S. Patent 1771976 granted to Coffey and Humber on July 29, 1930. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1931Volume 4, Issue 12Page: 1589-1597KeywordsHormonesSarcoma Issue Published: 1 June 1931 PDF DownloadLoading ...
Preferences of Community Physicians for Cancer Screening Guidelines
Authors: Ronald Czaja
Journal: Annals of Internal Medicine (1994)

Objective: To assess factors related to consensus among community physicians regarding appropriate screening intervals for eight cancer screening procedures for which guidelines have been published. Design: Interviews were conducted with a national random sample of 3436 physicians in family practice, internal medicine, general surgery, and gynecology by mail or telephone or both. The overall response rate was 67%. Measurements: Consensus by specialization and by physician and practice characteristics on the appropriate screening intervals for early detection of cancers of the breast, cervix, colon and rectum, and lung for asymptomatic adults at normal risk. Results: More than 60% of the physicians surveyed agreed on the length of the screening intervals for six of eight procedures. Consensus most closely followed American Cancer Society- and National Cancer Institute-recommended screening intervals for all procedures except chest roentgenogram. Acceptance of screening intervals was not related to the extent of agreement among published guidelines. Surgeons tended to favor more aggressive screening than family physicians and internists; gynecologists most consistently favored aggressive screening for cancers occurring in women. Older physicians and those in solo practice tended to favor outmoded procedures such as routine chest roentgenograms and to be more conservative about screening intervals. Conclusions: Physicians stated that they follow the American Cancer Society and National Cancer Institute guidelines for cancer screening more than the guidelines published by their own specialty societies, but they also reported procedures not recommended in any guidelines. These findings suggest that changing physician screening practices will be difficult.
THE BLOOD SERUM IN PERNICIOUS ANAEMIA: With Notes on the Nature of the Disease and its Treatment. A Preliminary Note
Authors: E. M. Brockbank
Journal: BMJ (1922)

I am of opinion that the toxic action of salvarsan compounds on the liver is not sufficiently borne in mind in the very extensive use of this drug at the present day.Professor Maclean has guggested that liver damage is less likely to follow salvarsan administration if the liver cells hiave stored in them a certain amount of glycogen, and he has recom- mended that danger may be avoided by taiing glucose slhortly before tlle drug is given.' This precautioin is undoubtedly of value, and it lhas been emphasized by tlhe use of a drua having like effects on tlhe liver namely, clhloroform in its production of delayed chloroform poisoninig after anaestlhesia.I wislh to express my sincere thianks to.Mr. J. Webster and
Narrative Review: The Enigma of Pulmonary Arterial Hypertension: New Insights from Genetic Studies
Authors: John H. Newman, John A. Phillips, James E. Loyd
Journal: Annals of Internal Medicine (2008)

Pulmonary arterial hypertension (PAH) occurs as an idiopathic disease (formerly called primary pulmonary hypertension) and as a consequence of other illnesses. These illnesses include connective tissue diseases, portal hypertension, diet and stimulant drug use, HIV infection, and congenital heart disease. Inherited susceptibility to PAH occurs in families and is almost always due to mutations in genes of the TGF-beta family of receptors. The most common mutation leading to PAH is in bone morphogenetic protein receptor type 2 (BMPR2), originally discovered to be involved in bone healing. Mutations in BMPR2 have also been found in patients with idiopathic PAH, although the true prevalence of this susceptibility has not been determined. About 20% of individuals with a BMPR2 mutation develop symptomatic pulmonary hypertension. Evidence is growing that imbalanced activation of other TGF-beta receptors coupled with reduced activity of mutated BMPR2 increases the likelihood of development of PAH. Many signaling systems have been found to participate in PAH, including K channels, serotonin, angiopoietin, and cyclooxygenases. An interaction of these signaling systems with BMPR2 is a focus of research in PAH. Approaches to altering the imbalance of activation of BMPR2 and other TGF-beta receptors may yield future therapies for PAH.
Cerebral Apoplexy: With Some General and Statistical Observations on the Causes of the Disease, and the Relative Frequency of its Occurrence at Different Periods of Life
Authors: R. Quain
Journal: BMJ (1849)

given way in a day or two after the stitches have been withdrawn, seemingly in consequence of the contraction induced by the soft struc- tures resuming their original attachment to the bones.Sometimes a small slough has formed in this locality, but I have not perceived that the opening has been larger on this account after the parts had been completely healed; the size of the fissure here being regulated chiefly by the deficiency of the bones.(To be concluded in next n?Kher.)
AT THE PUBLIC DISPENSARY WITH WILLAN AND BATEMAN*
Authors: HENRY MacCORMAC
Journal: British Journal of Dermatology (1933)

Journal Article AT THE PUBLIC DISPENSARY WITH WILLAN AND BATEMAN Get access HENRY MacCORMAC, C.B.E., M.D., F.R.C.P. HENRY MacCORMAC, C.B.E., M.D., F.R.C.P. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 45, Issue 10, 1 October 1933, Pages 385–395, https://doi.org/10.1111/j.1365-2133.1933.tb10109.x Published: 01 October 1933