tbuckley/cabot-search huggingface dataset:
Metabolic Response during Impending Myocardial Infarction
Authors: L. H. OPIE
Journal: Circulation (1972)

Both glucose and free fatty acids (FFA) are major fuels for the normally oxygenated heart with the dominant contribution being derived from glucose in the resting, fed state and FFA in the resting, fasted state. In anoxia, all energy must be produced anaerobically from glycogen or glucose. Anoxia by itself accelerates glycolysis, but further increases may follow an increased circulating glucose concentration and the addition of insulin. Even maximal rates of anaerobic glycolysis, achieved at high coronary flow rates, can only sustain the energy needs of the K + -arrested heart but not of the working heart. FFA cannot be utilized for energy in anoxia and may accumulate intracellularly as triglyceride or FFA. From these and other animal data have grown the concepts that glucose is "good" for the survival of the ischemic heart, and that FFA is "bad." However, glucose-fatty acid interaction has not been well studied in the infarcting, ischemic myocardium. While a "toxic" effect of FFA has been shown in many experimental models, there are other reports of increased FFA concentrations having no harmful effect or even a beneficial effect on the infarcting myocardium. The possible benefits of administration of glucose (with insulin) to patients with acute myocardial infarction could only be assessed by a controlled therapeutic trial.
Immune modulation of metalloproteinase production in human macrophages. Selective pretranslational suppression of interstitial collagenase and stromelysin biosynthesis by interferon-gamma.
Authors: S D Shapiro, E J Campbell, D K Kobayashi, H G Welgus
Journal: Journal of Clinical Investigation (1990)

Interferon-gamma (IFN-gamma) is a lymphokine that activates mononuclear phagocytes. To test the hypothesis that IFN-gamma might have important effects upon the ability of human mononuclear phagocytes to degrade extracellular matrix, we have studied the action of this cytokine on the production of metalloproteinases and the counterregulatory tissue inhibitor of metalloproteinases (TIMP) by the human alveolar macrophage. We have found that IFN-gamma potently and selectively suppresses the lipopolysaccharide-induced production of two metalloproteinases--interstitial collagenase and stromelysin--by 50-90% at doses greater than or equal to 10 U/ml. The synthesis of TIMP and 92-kD type IV collagenase was also diminished by IFN-gamma, but these responses required 50- to 100-fold higher concentrations of the cytokine. All doses of IFN-gamma increased total and secreted protein synthesis slightly, indicating a highly specific effect on metalloenzyme biosynthesis. Inhibition of metalloproteinase expression occurred at a pretranslational level, as evidenced by parallel reductions in enzyme biosynthesis and collagenase-specific steady-state mRNA levels. Interestingly, the effect of IFN-gamma on metalloenzyme production was not readily reversible. Therefore, while IFN-gamma activates the macrophage and renders it tumoricidal, this enhanced function appears to be attained at the expense of the cell's capacity to degrade extracellular matrix.
Mitogen-inducible gene-6 is a negative regulator of epidermal growth factor receptor signaling in hepatocytes and human hepatocellular carcinoma
Authors: Markus Reschke, Ingvar Ferby, Ewa Stepniak, Nina Seitzer, David Horst, Erwin F. Wagner, Axel Ullrich
Journal: Hepatology (2009)

The mitogen-inducible gene-6 (mig-6) is a multi-adaptor protein implicated in the regulation of the HER family of receptor tyrosine kinases. We have reported recently that mig-6 is a negative regulator of epidermal growth factor receptor (EGFR)-dependent skin morphogenesis and tumor formation in vivo. In the liver, ablation of mig-6 leads to an increase in EGFR protein levels, suggesting that mig-6 is a negative regulator of EGFR function. In line with this observation, primary hepatocytes isolated from mig-6 knockout and wild-type control mice display sustained mitogenic signaling in response to EGF. In order to explore the role of mig-6 in the liver in vivo, we analyzed liver regeneration in mig-6 knockout and wild-type control mice. Interestingly, mig-6 knockout mice display enhanced hepatocyte proliferation in the initial phases after partial hepatectomy. This phenotype correlates with activation of endogenous EGFR signaling, predominantly through the protein kinase B pathway. In addition, mig-6 is an endogenous inhibitor of EGFR signaling and EGF-induced tumor cell migration in human liver cancer cell lines. Moreover, mig-6 is down-regulated in human hepatocellular carcinoma and this correlates with increased EGFR expression. Conclusion: Our data implicate mig-6 as a regulator of EGFR activity in hepatocytes and as a suppressor of EGFR signaling in human liver cancer. (HEPATOLOGY 2009.)
Ventilation-Perfusion Mismatch in Tumor Embolism
Authors: ROBERT J. BOUDREAU, ROBERT LISBONA, H SHELDON
Journal: Clinical Nuclear Medicine (1982)

An unusual case of extensive tumor embolism is reported in which the lung scan was instrumental in demonstrating the underlying pathophysiology. Pulmonary arteriography failed to demonstrate vessel occlusion and the need to perform this study with special care is re-emphasized. A brief review of the literature indicates that tumor embolism occurs much more frequently than is clinically suspected.
A History of Epidemics in Britain
Authors: Lester S. King
Journal: JAMA (1965)

To the delight of historians, epidemiologists, and sociologists, Creighton's classic text is again available. Inadequately appreciated at the time of its publication, the book has steadily grown in stature. Charles Creighton (1847-1927) received his MD degree in 1871 and soon turned to pathology. While he achieved considerable recognition in this field, he could not accept the newer concepts of bacteriology that developed in the 1880's. He held unusual views on tuberculosis and engaged in unfortunate disputes on vaccination. Indeed, he acquired a reputation as an anti-vaccinationist and gradually was ostracized by the medical world. By the end of the first decade of the 20th century he had lapsed into virtual oblivion. His<i>History of Epidemics</i>, published in two volumes in 1891 and 1894, was far ahead of its time. The valuable portions lie in the painstaking and critical collection of original sources bearing on epidemics, and the consideration of epidemiology
Poor countries make the best teachers: discuss
Authors: Tessa Richards, James Tumwine
Journal: BMJ (2004)

Poor countries make the best teachers: discuss It is not only what you spend on health but how you spend itWe will meet in the developing world a level of will, skill, and constancy that may put ours to shame.We may find ourselves not the teachers we thought we were, but students of those who work under circumstances that would have stopped us long ago. 1
Cadmium Induces the Expression of Grp78, an Endoplasmic Reticulum Molecular Chaperone, in LLC-PK1 Renal Epithelial Cells
Authors: Fang Liu, Kiyoshi Inageda, Gen Nishitai, Masato Matsuoka
Journal: Environmental Health Perspectives (2006)

To reveal the effects of cadmium exposure on the endoplasmic reticulum (ER) stress response, we examined the expression and function of 78-kDa glucose-regulated protein (Grp78) , an ER-resident molecular chaperone, in LLC-PK1 cells. In cells treated with 10 microM cadmium chloride, Grp78 protein levels increased after 6 hr and remained elevated at 24 hr. When cells were incubated with 1-20 microM CdCl2 for 6 hr, Grp78 increased in a dose-dependent manner. In addition, Grp78 mRNA levels were elevated in response to CdCl2 exposure. After exposure to 10 microM CdCl2, the levels of activating transcription factor 4 (ATF4) were increased at 2 hr, with a further enhancement after that ; this accumulation followed the transient but marked phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2(alpha)) on serine 51. Although ATF4 mRNA levels increased mildly by CdCl2 exposure, treatment with actinomycin D did not suppress CdCl2-induced accumulation of ATF4 protein, suggesting the involvement of posttranscriptional and, in part, transcriptional mechanisms. Compared with other heavy-metal compounds such as manganese chloride, zinc chloride, mercuric chloride, and lead chloride, CdCl2 could increase the levels of Grp78, ATF4, and the phosphorylated form of eIF2(alpha) more markedly without definite cellular damage. The silencing of Grp78 expression using short-interference RNA enhanced CdCl2-induced cellular damage. These results show that cadmium induces the expression of Grp78 probably via phosphorylation of eIF2(alpha) and resultant translation of ATF4, and this ER stress response plays a role in protection against cadmium cytotoxicity in this renal epithelial cell.
Retail Clinics and Drugstore Medicine
Authors: Christine K. Cassel
Journal: JAMA (2012)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Mechanisms of Thrombus Formation
Authors: Bruce Furie, Barbara C. Furie
Journal: New England Journal of Medicine (2008)

Hemostasis is the process that maintains the integrity of a closed, high-pressure circulatory system after vascular damage. Vessel-wall injury and the extravasation of blood from the circulation rapidly initiate events in the vessel wall and in blood that seal the breach. Circulating platelets are recruited to the site of injury, where they become a major component of the developing thrombus; blood coagulation, initiated by tissue factor, culminates in the generation of thrombin and fibrin. These events occur concomitantly (Figure 1A; also see Video, available with the full text of this article at www.nejm.org), and under normal conditions, regulatory mechanisms contain . . .
ROS-dependent activation of the TRAF6-ASK1-p38 pathway is selectively required for TLR4-mediated innate immunity
Authors: Atsushi Matsuzawa, Kaoru Saegusa, Takuya Noguchi, Chiharu Sadamitsu, Hideki Nishitoh, Shigenori Nagai, Shigeo Koyasu, Kunihiro Matsumoto, Kohsuke Takeda, Hidenori Ichijo
Journal: Nature Immunology (2005)
Extracellular vesicles and reproduction–promotion of successful pregnancy
Authors: Dionne Tannetta, Rebecca Dragovic, Zahraa Alyahyaei, Jennifer Southcombe
Journal: Cellular and Molecular Immunology (2014)

Extracellular vesicles (EVs) are membrane-bound complexes secreted from cells under both physiological and pathological conditions. They contain proteins, nucleic acids and lipids and act as messengers for cell-cell communication and signalling, particularly between immune cells. EV research is a rapidly evolving and expanding field, and it appears that all biological fluids contain very large numbers of EVs; they are produced from all cells that have been studied to date, and are known to have roles in several reproductive processes. This review analyses the evidence for the role of EVs throughout human reproduction, starting with the paternal and maternal gametes, followed by the establishment and continuation of successful pregnancies, with specific focus, where possible, on the interaction of EVs with the maternal immune system. Importantly, variations within the EV populations are identified in various reproductive disorders, such as pre-term labour and pre-eclampsia.
Medical Practice under the Clinton Reforms -- Avoiding Domination by Business
Authors: A S Relman
Journal: New England Journal of Medicine (1993)

The Clinton proposal for health care reform is based on managed competition, as are the alternatives offered by Republicans in the Senate and by a bipartisan group in the House of Representatives. So the odds are good that managed competition will be part of the final health reform legislation, whatever changes Congress may decide to make in the rest of the Clinton proposal.Managed competition, as almost everyone knows by now, means regulated competition among managed-care plans. Under the Clinton proposal medical care would be delivered by managed-care entities called “health plans,” which would provide a uniform package of medical . . .
On the Mode of Performing the Operation of Ventro-Fixation of the Uterus, or Hysteropexy, in Cases of Intractable Retroflexion
Authors: J. Braithwaite
Journal: BMJ (1894)

CIHLOROSIS WITII SYMPTOMS OF IBRAIN DISEASE.[IML2I& 1073 and all thle patients died of seconlary ha,morrlage with the eiception ot two, who (tied before the usual period wlhen tlhis came on.So maniy branches come oil from this part of thl vessel that no satisfactory clot is formed.On the left si(le Sir AstleY ('ooPer failed to secuire the vessel, and is said to have wounded thie tlhoracic duct.This deterred me from attenipt- ilng ligature even witlh our modern absorbable lig.atures on the metlhod whtichl aims at tlhei non-division of the inner and jmiddle (oats.
AMBLYOPIA FROM AUTO-INTOXICATION.
Authors: H. B. YOUNG
Journal: JAMA (1898)

Within the past year I have had under observation six cases of amblyopia differing in degree, and more or less transitory in character, for which I have been at a loss to give a definitive diagnosis. The possibility of an hysteric origin has not been overlooked. Indeed with two of the six this idea is still entertained. But with the others, the presence of a particular symptom, coupled with intestinal derangement, and this more or less uniform in all, seems to allow the characterization which appears in the title of this paper. I will endeavor to describe briefly these four cases: <h3>Case 1.</h3> —Mrs. C. S., age 40, mother of four children, hitherto vivacious and apparently healthy, aborted lastMay in the sixth week of her pregnancy. She was making good progress toward recovery under the care of her family physician, when on the evening of the third day, without any
Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture
Authors: Xingnan Li, Lincoln Nadauld, Akifumi Ootani, David C Corney, Reetesh K Pai, Olivier Gevaert, Michael A Cantrell, Paul G Rack, James T Neal, Carol W-M Chan, Trevor Yeung, Xue Gong, Jenny Yuan, Julie Wilhelmy, Sylvie Robine, Laura D Attardi, Sylvia K Plevritis, Kenneth E Hung, Chang-Zheng Chen, Hanlee P Ji, Calvin J Kuo
Journal: Nature Medicine (2014)
Activation of the respiratory burst enzyme from human neutrophils in a cell-free system. Evidence for a soluble cofactor.
Authors: L C McPhail, P S Shirley, C C Clayton, R Snyderman
Journal: Journal of Clinical Investigation (1985)

Activation of the respiratory burst in phagocytic cells, an important host defense process, is not yet well understood. We now report the development of a cell-free system for activation of NADPH oxidase, the respiratory burst enzyme, in human neutrophils. Activation was achieved by the addition of arachidonic acid to a postnuclear supernatant (500 g) from disrupted unstimulated cells (no arachidonate, 0.2; with arachidonate, 3.4 nmol superoxide anion/min per mg) and was dependent on both the concentration of arachidonate and on the amount of cellular material present. Activity stimulated by arachidonate appeared to be NADPH oxidase based on a Michaelis constant for NADPH of 32 microM and a pH optimum of 7.0-7.5. Separation of the 500-g supernatant by high speed centrifugation revealed a requirement for both soluble and particulate cofactors. Activation of NADPH oxidase by arachidonate did not occur in the high speed pellet fraction from unstimulated cells but could be restored by the addition of the high speed supernatant. In addition, priming of intact neutrophils with low concentrations of the chemoattractant N-formyl-methionyl-leucyl-phenylalanine or the tumor promoter phorbol myristate acetate replaced the soluble factor requirement for NADPH oxidase activation by arachidonate in the high speed pellet. This cell-free system can now be used to provide further insight into the biochemical basis of priming and the terminal mechanisms involved in the activation of NADPH oxidase.
IS INCREASED INTESTINAL PERMEABILITY ASSOCIATED WITH ALTERED INFLAMMATORY BALANCE AND CORONARY ARTERY DISEASE?
Authors: Luigi M. Biasucci, Alessia Romito, Maria Giulia Marini, Annalisa Caroli, Chiara Sonnino, Sara Ucci, Giovanna Liuzzo, Venanzio Valenza, Francesca Graziani, Filippo Crea
Journal: Journal of the American College of Cardiology (2014)
Left Heart Hemodynamics During Angina Pectoris Induced by Atrial Pacing
Authors: JOSEPH W. LINHART, FRANK J. HILDNER, S. SERGE BAROLD, JOHN W. LISTER, PHILIP SAMET
Journal: Circulation (1969)

In order to determine the associated hemodynamic events, angina pectoris was induced by an atrial pacing technic. In all patients developing angina pectoris, ischemic changes were noted electrocardiographically. The hemodynamic findings were variable: in some patients no changes were noted; in others, significant increases in cardiac output, left ventricular end-diastolic pressures (LVEDP), and femoral arterial and pulmonary arterial pressures occurred. These changes suggest that, initially, ischemia produces a decrease in myocardial compliance and this may also be associated with enhanced sympathetic nervous system activity. Myocardial failure may subsequently ensue, however. The administration of nitroglycerin, during angina at a fixed rapid heart rate, resulted in a reduction in LVEDP and cardiac work. Chest pain was always relieved following these hemodynamic changes, indicating a dependence upon these changes for the effectiveness of nitroglycerin.
Once-daily simeprevir (TMC435) with pegylated interferon and ribavirin in treatment-naïve genotype 1 hepatitis C: The randomized PILLAR study
Authors: Michael W. Fried, Maria Buti, Gregory J. Dore, Robert Flisiak, Peter Ferenci, Ira Jacobson, Patrick Marcellin, Michael Manns, Igor Nikitin, Fred Poordad, Morris Sherman, Stefan Zeuzem, Jane Scott, Leen Gilles, Oliver Lenz, Monika Peeters, Vanitha Sekar, Goedele De Smedt, Maria Beumont-Mauviel
Journal: Hepatology (2013)

The phase IIb, double-blind, placebo-controlled PILLAR trial investigated the efficacy and safety of two different simeprevir (SMV) doses administered once-daily (QD) with pegylated interferon (Peg-IFN)-α-2a and ribavirin (RBV) in treatment-naïve patients with HCV genotype 1 infection. Patients were randomized to one of five treatments: SMV (75 or 150 mg QD) for 12 or 24 weeks or placebo, plus Peg-IFN and RBV. Patients in the SMV arms stopped all treatment at week 24 if response-guided therapy (RGT) criteria were met; patients not meeting RGT continued with Peg-IFN and RBV until week 48, as did patients in the placebo control group. Sustained virologic response (SVR) rates measured 24 weeks after the planned end of treatment (SVR24) were 74.7%-86.1% in the SMV groups versus 64.9% in the control group (P < 0.05 for all comparisons [SMV versus placebo], except SMV 75 mg for 24 weeks). Rapid virologic response (HCV RNA <25 IU/mL undetectable at week 4) was achieved by 68.0%-75.6% of SMV-treated and 5.2% of placebo control patients. According to RGT criteria, 79.2%-86.1% of SMV-treated patients completed treatment by week 24; 85.2%-95.6% of these subsequently achieved SVR24. The adverse event profile was generally similar across the SMV and placebo control groups, with the exception of mild reversible hyperbilirubinemia, without serum aminotransferase abnormalities, associated with higher doses of SMV.SMV QD in combination with Peg-IFN and RBV significantly improves SVR rates, compared with Peg-IFN and RBV alone, and allows the majority of patients to shorten their therapy duration to 24 weeks.
Distal Protection Improved Reperfusion and Reduced Left Ventricular Dysfunction in Patients With Acute Myocardial Infarction Who Had Angioscopically Defined Ruptured Plaque
Authors: Isamu Mizote, Yasunori Ueda, Tomohito Ohtani, Masahiko Shimizu, Yasuharu Takeda, Takafumi Oka, Masahiko Tsujimoto, Atsushi Hirayama, Masatsugu Hori, Kazuhisa Kodama
Journal: Circulation (2005)

Distal protection, in the Saphenous Vein Graft Angioplasty Free of Emboli (SAFER) trial, is demonstrated to prevent distal embolism in the percutaneous coronary intervention of saphenous vein graft. However, in the Enhanced Myocardial Efficacy and Recovery by Aspiration of Liberated Debris (EMERALD) trial, it was not effective in the percutaneous coronary intervention of native coronary arteries in patients with acute myocardial infarction (AMI). We hypothesized that its effectiveness would be determined by lesion characteristics. Therefore, we classified the type of culprit lesion by angioscopy and examined its influence on the effectiveness of distal protection, comparing patients with AMI treated with and without distal protection.Consecutive patients with AMI treated without distal protection (n=110) from July 2000 to July 2002 and those treated with distal protection (n=81) from July 2002 to July 2004 were included. Patients in each group were subdivided according to whether or not they had angioscopically defined ruptured plaque at culprit lesion. Among those groups, incidence of no-reflow phenomenon, ST-segment resolution, myocardial blush grade, and left ventricular ejection fraction at 6 months were compared. Aspirated samples by distal protection were semiquantitatively and histologically analyzed and compared between patients with and without ruptured plaque. No-reflow phenomenon was most frequently (P<0.05) observed in patients with ruptured plaque treated without distal protection. ST-segment resolution (68+/-15% versus 40+/-21%, P<0.001), myocardial blush grade (2.6+/-0.5 versus 1.8+/-0.3, P<0.001), and left ventricular ejection fraction (47.2+/-6.7% versus 41.0+/-9.7%, P<0.01) were improved by distal protection among patients with ruptured plaque but not among patients without ruptured plaque. Aspirated samples >1 mm were detected more frequently (97.3% versus 78.5%, P<0.05) in patients with ruptured plaque than those without ruptured plaque. Histologically, aspirated samples contained plaque debris (95.3% versus 31.1%, P<0.05) more frequently in patients with ruptured plaque than in those without ruptured plaque.Distal protection reduced microcirculation damage and left ventricular dysfunction in patients with AMI who had angioscopically defined ruptured plaque. Distal embolization of plaque debris was detected more frequently in patients with ruptured plaque. These results suggest that microcirculation damage and left ventricular dysfunction are increased mainly by distal embolization of plaque debris rather than of thrombus.