tbuckley/cabot-search huggingface dataset:
Attenuation by Gemfibrozil of Expression of Plasminogen Activator Inhibitor Type 1 Induced by Insulin and its Precursors
Authors: Thomas K. Nordt, Katharina Kornas, Karlheinz Peter, Satoshi Fujii, Burton E. Sobel, Wolfgang Ku¨bler, Christoph Bode
Journal: Circulation (1997)

Background Insulin and its precursors found in increased plasma concentrations in non–insulin-dependent diabetes mellitus (NIDDM) augment synthesis of plasminogen activator inhibitor type 1 (PAI-1) in Hep G2 cells in vitro and in rabbit liver in vivo. Reduced endogenous fibrinolysis secondary to increased PAI-1 activity may exacerbate atherogenesis. Recently, the reduction of the coronary heart disease incidence in the Helsinki Heart Study has implicated favorable modulation of endogenous fibrinolysis by gemfibrozil. Methods and Results In Hep G2 cells, 500 (700) μmol/L gemfibrozil decreased basal secretion of PAI-1 by 26% (43%) ( P =.012 and P =.021, respectively) and attenuated insulin-induced (10 nmol/L) augmentation of PAI-1 in conditioned media by 61% (109%) ( P =.010) within 24 hours. Inhibition was dependent on the duration of exposure (0 to 48 hours) and on the concentration of gemfibrozil (0 to 700 μmol/L) but not on the concentration of insulin (0.1 to 100 nmol/L). Gemfibrozil attenuated the augmentation of PAI-1 secretion induced by proinsulin (&gt;100%), by des(31,32)proinsulin (75%), and by des(64,65)proinsulin (77%) as well (10 nmol/L each). The specificity of these effects was confirmed by the unaltered levels of newly synthesized protein (metabolic labeling) and of total protein (both in conditioned media and cell lysates). Secretion of fibrinogen by Hep G2 cells was not affected by gemfibrozil. Changes in PAI-1 protein levels reflected modulation of PAI-1 gene expression as manifested by changes in levels of 3.2-kb PAI-1 mRNA (Northern blots). Conclusions Gemfibrozil attenuated the augmentation of synthesis and secretion of PAI-1 induced by insulin and its precursors directly and specifically. Accordingly, gemfibrozil may exert favorable therapeutic effects normalizing impaired fibrinolysis in patients with hyperinsulinemia such as NIDDM.
"COUGH AS A MANIFESTATION OF HYPERSENSITIVENESS"
Authors: George L. Waldbott
Journal: JAMA (1930)

<h3>To the Editor:</h3> —In the article by Colmes and Rackemann on "Cough as a Manifestation of Human Hypersensitiveness" (The Journal, July 19), the statement is made that "allergic cough (without the presence of wheezing or râles in the chest) has not been emphasized in the literature." In an article on "Allergic Bronchitis" (<i>J. Lab. &amp; Clin. Med.</i><b>13</b>:943 [July] 1928, abstracted inThe Journal, Sept. 1, 1928, p. 676) I have given a summary of the literature available on this subject and a detailed description of the clinical picture of this condition with case reports similar to the ones described. In the discussion of this paper before the Association for the Study of Allergy (The Journal, Oct. 20, 1928, p. 1220) the resemblance of this cough to pertussis and its importance in the diagnosis of incipient bronchial asthma was emphasized. In a recent publication (<i>Klin. Wchnschr.</i><b>9</b>:220 [Feb.]
Kinking of the Brachial Artery
Authors: Daniel F. Casten, Donald Forman
Journal: New England Journal of Medicine (1962)

ARTERIOSCLEROTIC disease of the major vessels may result in elongation, tortuosity, kinking or aneurysm formation. Aneurysms of the abdominal aorta are relatively common, and tortuosity and elongation of the thoracic aorta also occur rather frequently. Kinking of the carotid artery has been documented by Deterling,1 but kinking of the brachial artery has not been reported hitherto.This report details the first reported case of kinking of the brachial artery. As pointed out by Deterling,1 kinking of a peripheral artery may masquerade as an aneurysm. This was the clinical diagnosis in the present case, but arteriography clearly delineated the exact nature . . .
Extensive Pelvic Infarction Diagnosed by Radionuclide Skeletal and Bone Marrow Imaging
Authors: ANDREW E. SOUTHEE, KENNETH J. LEE, MONICA A. ROSSLEIGH, JOHN G. MORRIS
Journal: Clinical Nuclear Medicine (1988)

A case of extensive pelvic infarction, where radionuclide studies provided the initial diagnosis and have shown subsequent evolutionary changes, is presented. Radiographs were initially normal and only became abnormal after 12 months.
Abstract 1855: Regulation of proliferation of colon cancer cells by compounds affecting glycolysis including 3-bromopyruvate, 2-deoxyglucose and biguanides.
Authors: Michael A. Lea, Mehreen Qureshi, Michael Buxhoeveden, Nicolette Gengel, Jessica Kleinschmit, Charles desBordes
Journal: Cancer Research (2013)

Abstract In earlier work we found that incubation of colon cancer cells with 2-deoxyglucose had an additive inhibitory effect on proliferation with the biguanides, metformin and phenformin, and blocked the acidification of the medium caused by incubation of cells with biguanides. In the present work, studies were performed with Caco-2, HCT116, HT29 and SW1116 colon cancer cells. Metabolism of glucose and acidification of the medium was greater with the more rapidly proliferating cells being greatest with HCT116 cells and least with SW1116 cells. We have seen that, as with 2-deoxyglucose, 3-bromopyruvate can also prevent the lowering of medium pH caused by biguanide treatment. . Inhibition of glucose metabolism paralleled the decrease in acidification of the medium. 3-bromopyruvate inhibited colon cancer cell proliferation. Additive effects with metformin and 3-bromopyruvate were not observed in any of the four colon cancer cell lines but some additive effects were seen with phenformin and 3-bromopyruvate. An additive effect was more notable in combined treatment with 3-bromopyruvate and 2-deoxyglucose. Induction of alkaline phosphatase activity serves as a marker of differentiation in colon cancer cells. The induction of alkaline phosphatase activity by butyrate was not consistently affected by combination with other agents that modified glucose metabolism. The drug combinations that were examined inhibited proliferation in wild type and P53 null HCT116 cells and affected colon cancer lines with different growth rates. Although metformin and phenformin increase glucose metabolism by colon cancer cells while 3-bromopyruvate and 2-deoxyglucose inhibit glucose metabolism, all these compounds have potential inhibitory action on the proliferation of colon cancer cells. Citation Format: Michael A. Lea, Mehreen Qureshi, Michael Buxhoeveden, Nicolette Gengel, Jessica Kleinschmit, Charles desBordes. Regulation of proliferation of colon cancer cells by compounds affecting glycolysis including 3-bromopyruvate, 2-deoxyglucose and biguanides. [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 1855. doi:10.1158/1538-7445.AM2013-1855
The Role of Public-Sector Research in the Discovery of Drugs and Vaccines
Authors: Ashley J. Stevens, Jonathan J. Jensen, Katrine Wyller, Patrick C. Kilgore, Sabarni Chatterjee, Mark L. Rohrbaugh
Journal: New England Journal of Medicine (2011)

Historically, public-sector researchers have performed the upstream, basic research that elucidated the underlying mechanisms of disease and identified promising points of intervention, whereas corporate researchers have performed the downstream, applied research resulting in the discovery of drugs for the treatment of diseases and have carried out development activities to bring them to market. However, the boundaries between the roles of the public and private sectors have shifted substantially since the dawn of the biotechnology era, and the public sector now has a much more direct role in the applied-research phase of drug discovery.We identified new drugs and vaccines approved by the Food and Drug Administration (FDA) that were discovered by public-sector research institutions (PSRIs) and classified them according to their therapeutic category and potential therapeutic effect.We found that during the past 40 years, 153 new FDA-approved drugs, vaccines, or new indications for existing drugs were discovered through research carried out in PSRIs. These drugs included 93 small-molecule drugs, 36 biologic agents, 15 vaccines, 8 in vivo diagnostic materials, and 1 over-the-counter drug. More than half of these drugs have been used in the treatment or prevention of cancer or infectious diseases. PSRI-discovered drugs are expected to have a disproportionately large therapeutic effect.Public-sector research has had a more immediate effect on improving public health than was previously realized.
Reactivation of a major histocompatibility complex class II gene in mouse plasmacytoma cells and mouse T cells.
Authors: C H Chang, W L Fodor, R A Flavell
Journal: The Journal of Experimental Medicine (1992)

Terminally differentiated plasma cells and mouse T cells do not express major histocompatibility complex (MHC) class II genes although class II gene expression is observed in pre-B and mature B cells as well as in activated human T cells. Transient heterokaryons were prepared and analyzed to investigate the mechanisms of inactivation of MHC class II gene in mouse plasmacytoma cells and mouse T cells. The endogenous MHC class II genes in both mouse plasmacytoma cells and mouse T cells can be reactivated by factors present in B cells. This reactivation of class II gene is also observed by fusion with a human T cell line which expresses MHC class II genes, but not with a class II negative human T cell line. It appears that the loss of MHC class II gene expression during the terminal differentiation of B cells or T cell lineage is due to absence of positive regulatory factor(s) necessary for class II transcription.
Association of Angiotensin I-Converting Enzyme Gene Polymorphism With Myocardial Ischemia and Patency of Infarct-Related Artery in Patients With Acute Myocardial Infarction
Authors: Habib A. Dakik, John J. Mahmarian, Mario S. Verani, John A. Farmer, Guiling Zhao, Ali J. Marian
Journal: Journal of the American College of Cardiology (1997)
Metformin in Heart Failure
Authors: Silvio E. Inzucchi, Frederick A. Masoudi, Darren K. McGuire
Journal: Diabetes Care (2007)

We recently learned of an important change in the prescribing information for metformin, previously contraindicated in patients with type 2 diabetes accompanied by heart failure (HF) requiring pharmacological therapy. The contraindication was introduced to the label soon after the drug's U.S. release, when case reports emerged of HF patients taking metformin who developed lactic acidosis. It was never clear, however, whether either the HF or the medication were contributing factors. Subsequent analyses revealed a miniscule risk of lactic acidosis associated with metformin …
Predictions of Hospital Mortality Rates: A Comparison of Data Sources
Authors: Michael Pine
Journal: Annals of Internal Medicine (1997)

Comparing hospital mortality rates requires accurate adjustment for patients' intrinsic differences. Commercial severity systems require either administrative data that omit vital clinical facts about patients' conditions at hospital admission or costly, time-consuming abstraction of medical records. The validity of supplementing administrative data with laboratory data has not been assessed.To compare risk-adjusted mortality predictions using administrative data alone; administrative data plus laboratory values; and the combination of administrative, laboratory, and clinical data.Retrospective cohort study.30 acute care hospitals.46,769 patients hospitalized with acute myocardial infarction, cerebrovascular accident, congestive heart failure, or pneumonia.Each patient's probability of dying was estimated by using administrative data only (unrestricted administrative models), administrative data restricted to secondary diagnoses that are unlikely to be hospital-acquired complications (restricted administrative models), restricted administrative data plus laboratory data (laboratory models), and restricted administrative data plus laboratory and abstracted clinical data (clinical models).The unrestricted administrative models predicted death better than the restricted administrative models (average areas under the receiver-operating characteristic [ROC] curves, 0.87 and 0.75, respectively) and as well as the laboratory models and the clinical models (average areas under the ROC curves, 0.86 and 0.87, respectively). The good mortality predictions obtained by using the unrestricted administrative models result from inclusion of hospital-acquired complications that commonly precede death. The laboratory models ranked 93% of patients and 95% of hospitals in a manner similar to the clinical models; in comparison, rankings provided by the laboratory models were similar to those provided for 75% of patients and 69% of hospitals by the unrestricted administrative models and for 72% of patients and 77% of hospitals by the restricted administrative models.Adding laboratory data (often available electronically) to restricted administrative data sets can provide accurate predictions of inpatient death from acute myocardial infarction, cerebrovascular accident, congestive heart failure, or pneumonia. This alternative avoids the cost of data abstraction and the serious errors associated with using administrative data alone.
Non-biopsy detection of intestinal metaplasia and dysplasia in Barrett’s esophagus: a prospective multicenter study
Authors: P. Sharma, N. Marcon, S. Wani, A. Bansal, S. Mathur, R. Sampliner, C. Lightdale
Journal: Endoscopy (2006)

There have been no multicenter studies investigating the use of magnification chromoendoscopy (MCE) for the detection of intestinal metaplasia and dysplasia/cancer in Barrett's esophagus. Our aims were to assess the ability of MCE to predict the histological diagnosis (non-biopsy detection), to compare the yield of MCE-targeted versus random biopsies for dysplasia, and to compare procedure times.In this prospective multicenter study, patients with known or suspected Barrett's esophagus underwent MCE with indigo carmine dye staining. Three mucosal patterns (ridge/villous, circular, and irregular/distorted) were standardized, based on past experience. Mucosal patterns were noted and target biopsies were obtained only if irregular/distorted patterns were identified. Otherwise, random four-quadrant biopsies were obtained.A total of 56 patients (mean age 64 years, mean length of Barrett's esophagus 2.7cm) were prospectively evaluated: 38 patients (67.8 %) had ridge/villous patterns, four patients (7.1 %) had circular patterns, four patients (7.1 %) had irregular/distorted patterns, and ten patients (17.8 %) had a combination of patterns. Histologically, intestinal metaplasia was not shown in eight patients (14.2 %), nondysplastic Barrett's esophagus was diagnosed in 30 patients (53.5 %), low-grade dysplasia was detected in 12 patients (21.4 %), and high-grade dysplasia was detected in six patients (10.7 %). An irregular/distorted pattern either throughout the entire segment of Barrett's esophagus or in combination with a ridge/villous or circular pattern had a sensitivity or 83 %, a specificity of 88 %, a positive predictive value of 45 %, and a negative predictive value of 98 % for high-grade dysplasia. The yield of high-grade dysplasia was similar for the two techniques but the time taken to perform MCE was less than the time taken to perform random biopsies.An irregular/distorted pattern is specific for high-grade dysplasia and so it may not be necessary to perform biopsies in patients with ridge/villous or circular mucosal patterns.
The cases for and against prescribing generic drugs: don't take innovative research based pharmaceutical companies for granted.
Authors: J. M. Cruickshank
Journal: BMJ (1988)

The cases for and against prescribing generic drugs: don't take innovative research based pharmaceutical companies for granted John M Cruickshank In a cost conscious society the research based pharma- ceutical company is increasingly being portrayed as a profiteer and the company manufacturing generic drugs as a cutter of costs to the NHS.Clearly such an extreme view is both shortsighted and wrong, particu- larly as unreasonable profits are prevented by the direct control of the Department of Health.In putting the case for prescribing drugs with brand names both medical and economic arguments have to be con- sidered.
The Choroid Plexus in Systemic Lupus Erythematosus
Authors: CHRISTOPHER J. ATKINS
Journal: Annals of Internal Medicine (1972)

Gamma globulin deposits were found in the choroid plexus of two patients with systemic lupus erythematosus and mental disturbances but not in the choroid plexus of controls. The cerebrum, cerebellum, and brain stem were examined, but no striking neuropathologic or immunopathologic abnormalities were found in the brain substance or cerebral vessels. Immunological and electron microscopy studies suggest that these deposits are immune complexes, probably derived from the blood, like those deposited in the glomerulus in lupus nephritis. These previously unreported observations focus attention on the possible role of the choroid plexus in the pathogenesis of the nervous and mental manifestations of systemic lupus erythematosus.
Matricellular proteins in the heart: possible role during stress and remodeling
Authors: M SCHELLINGS
Journal: Cardiovascular Research (2004)

Matricellular proteins are extracellular matrix proteins that modulate cell–matrix interactions and cell function, and do not seem to have a direct structural role. The family includes tenascin-C (TN-C), tenascin-X (TN-X), osteonectin, osteopontin, thrombospondin-1 (TSP1) and thrombospondin-2 (TSP2). Expression of matricellular proteins is high during embryogenesis, but almost absent during normal postnatal life. Interestingly, it re-appears in response to injury. Left ventricular remodeling is a complicated process that occurs in the stressed heart, and is still not completely understood. Several members of the matricellular protein family, like tenascin-C, osteopontin, and osteonectin are up-regulated after cardiac injury. Therefore, this group of proteins may have crucial functions in the heart coping with stress. This review will focus on the expression, regulation and function of these matricellular proteins, and will discuss the crucial functions that these proteins might exert during remodeling of the stressed heart.
Cine magnetic resonance imaging after surgical repair in patients with transposition of the great arteries.
Authors: K J Chung, I A Simpson, R F Glass, D J Sahn, J R Hesselink
Journal: Circulation (1988)

Cine magnetic resonance imaging (MRI) was used for postoperative evaluation of eight patients who underwent intra-atrial baffle procedure for surgical repair of D-transposition of the great arteries (D-TGA). Their ages ranged from 9 months to 8 years. Younger patients were sedated with chloral hydrate (80 to 100 mg/kg) orally. MRI was performed with use of a General Electric Signa system operating at a field strength of 1.5 tesla. A body or head coil was used depending on the size of the patient. Images were obtained by use of a technique of gradient-recalled acquisition in steady state (GRASS) that utilizes a low flip angle and shorter repetition and echo times. Five patients had widely patent venae cavae and three had superior vena caval obstruction at the junction of the right atrium with a dilated azygos vein. There was no evidence of pulmonary venous obstruction in any of the patients. Right ventricular function was assessed in four patients and their ejection fractions ranged from 58% to 81%. Tricuspid and mitral regurgitation were observed in three and two patients, respectively. Both right and left ventricular outflow tracts were well visualized and showed no evidence of obstruction. Cine MRI is an entirely noninvasive, nonionizing, and safe procedure in young patients and appears to be a valuable alternative method for evaluating patients after surgical repair of D-TGA. With advancing technologies and an accumulation of experience with cine MRI, it appears that this new technique will play an important role in patient care for children with congenital heart disease.
Comparison of Adjuvant Chemotherapy With Methotrexate and Fluorouracil With and Without Cyclophosphamide in Breast Cancer Patients With One to Three Positive Axillary Lymph Nodes
Authors: C. L. Shapiro, R. S. Gelman, D. F. Hayes, R. Osteen, A. Obando, G. P. Canellos, E. Frei, I. C. Henderson
Journal: JNCI Journal of the National Cancer Institute (1993)

Background : Alkylating agents administered as single agents or incombination with antimetabolites or anthracyclines delay the appearance of metastases and prolong the survival of breast cancer patients after surgery. Purpose : This phase III clinical trial was designed to evaluate the therapeutic efficacy and toxicity of the alkylating agent cyclophosphamide in combination with the antimetabolites methotrexate and fluorouracil adjuvant to breast cancer surgery. Methods : This study consisted of 255 breast cancer patients ( a ) with one to three histologically positive axillary lymph nodes and either no detectable primary tumor or operable primary tumors 5 cm or less (T0-T2) (95% of the patients) or ( b ) with tumors larger than 5 cm (T3) and with negative axillary nodes. Patients were randomly allocated to receive either methotrexate (60 mg/m 2 ) and fluorouracil (600 mg/m 2 ) (MF) intravenously on days 1 and 8 every 28 days for eight cycles or cyclophosphamide (100 mg/m 2 ) orally on days 1–14 plus MF (CMF) every 28 days for the same duration. Median follow-up was 7.8 years, and maximum follow-up was 13 years. Results : There were no statistically significant differences in time to treatment failure or overall survival for patients treated with MF or CMF. At 8 years after completion of treatment, time to treatment failure was 55% (95% confidence interval [CI] = 50%–60%) and 59% (95% CI = 54%–64%) and overall survival was 69% (95% CI = 65%–73%) and 67% (95% CI = 62%–72%) for MF-and CMF-treated patients, respectively. The hazard ratios (MF to CMF) for time to treatment failure and for survival, estimated with a proportional hazards model, were 1.02 (95% CI = 0.69–1.50) and 0.87 (95% CI = 0.56–1.34), respectively. Myelosuppression was significantly greater (P<.0001) in CMF-treated patients during cycles 1–6. Median white blood cell count nadirs were between 4.4 × 10 3 /μL and 3.5 × 10 3 /μL in those receiving CMF. Dose reductions were more frequent in CMF-treated patients, which led to statistically significant differences (P<.0001) in amounts of methotrexate and fluorouracil administered. Primary cancers at other sites occurred in 14 patients (5.5%)—-six treated with MF and eight treated with CMF. Conclusions : Our findings suggest that the addition of cyclophosphamide to adjuvant chemotherapy with MF offers no therapeutic advantage but results in increased myelosuppression. Implications : Future trials will define the possible advantages of antimetabolites in adjuvant therapy. Further information will also become available when results of the ongoing National Surgical Adjuvant Breast and Bowel Project trial comparing adjuvant MF to CMF in node-negative breast cancer patients are presented. [J Natl Cancer Inst 85: 812–817, 1993]