tbuckley/cabot-search huggingface dataset:
Glucocorticoid Receptor Isoforms α and β in<i>in Vitro</i>Cytokine-induced Glucocorticoid Insensitivity
Authors: Alfons Torrego, Laura Pujols, Jordi Roca-Ferrer, Joaquim Mullol, Antoni Xaubet, César Picado
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

We stimulated peripheral blood mononuclear cells from 14 healthy subjects, 14 patients with stable asthma, and 13 patients with unstable asthma with interleukin (IL)-2 and IL-4 to induce glucocorticoid insensitivity and we examined the relationship between insensitivity and the expression of glucocorticoid receptor (GR) isoforms. Results are expressed as IC(50) (nanomolar) values (means +/- SD) in proliferation assays and as 10(3) cDNA molecules per microgram of total RNA (means +/- SD) in real-time polymerase chain reaction analysis. Cells from patients with unstable asthma were less sensitive (316 +/- 7 nM) to dexamethasone antiproliferative effects than those from healthy control subjects (102 +/- 4 nM, p < 0.05) and patients with stable asthma (107 +/- 2 nM, p < 0.05). Coincubation with IL-2 and IL-4 repressed the inhibitory effect of dexamethasone on proliferation in all groups (unstable: 851 +/- 47 nM, p < 0.01; stable: 912 +/- 52 nM, p = 0.001; control subjects: 537 +/- 45 nM, p = 0.001). GR-alpha mRNA baseline expression was higher in patients with unstable asthma [(1.95 +/- 0.40) x 10(3) cDNA molecules/microg total RNA, p < 0.05] than in patients with stable asthma [(1.46 +/- 0.35) x 10(3) cDNA molecules/microg total RNA] and healthy subjects [(1.35 +/- 0.25) x 10(3) cDNA molecules/microg total RNA]. GR-beta mRNA was 600 times lower than GR-alpha in the three groups. Coincubation with IL-2 and IL-4 significantly increased GR-alpha mRNA expression in the three groups (p < 0.01), but caused no significant change in GR-beta mRNA. GR-alpha, but not GR-beta, protein was detected at baseline and after cytokine exposure. Our data do not support the hypothesis that increased GR-beta expression can contribute to cytokine-induced glucocorticoid insensitivity.
Relationship between breathlessness and hypoxic and hypercapnic ventilatory response in patients with COPD
Authors: S Kobayashi, M Nishimura, M Yamomoto, Y Akiyama, K Miyamoto, Y Kawamaki
Journal: European Respiratory Journal (1996)

The purpose of this study is to examine the relationship between breathlessness and the ventilatory response to hypercapnia or hypoxia in patients with chronic obstructive pulmonary disease (COPD). Fifteen male patients (mean forced expiratory volume in one second (FEV1): 1.13 L) underwent tests to determine hyperoxic hypercapnic ventilatory response (HCVR) and isocapnic hypoxic ventilatory response (HVR) with simultaneous quantification of breathlessness by modified Borg scale. The ventilatory output was evaluated by the ratio of minute ventilation (V'E) divided by measured maximal voluntary ventilation (MVV). The magnitude of HCVR or HVR was assessed as the slope value of the V'E/MVV-end-tidal carbon dioxide pressure (PET,CO2) or arterial oxygen saturation (Sa,O2) regression line, respectively. The breathlessness during the tests was evaluated not only linearly in relation to V'E/MVV, but also at given levels of PET,CO2 or Sa,O2. The mean value of the breathlessness at two different levels of ventilation was greater during HVR than during HCVR, suggesting that hypoxia is dyspnogenic independently of ventilatory stimulation. The HCVR was inversely correlated with the breathlessness response to ventilation, while similar correlation was partly present for HVR. The HVR was positively correlated with the breathlessness at an Sa,O2 of 80%, whilst there was no such correlation between the HCVR and the breathlessness related to PET,CO2. Therefore, patients with a higher breathlessness related to increased ventilation had a lower HCVR and HVR, whilst those with a higher breathlessness with desaturation, which might include a direct influence of hypoxia, had a higher HVR. These findings suggest an interaction between ventilatory response and breathlessness during the test, which may partly include behavioural modulation of HCVR and HVR through the breathlessness in various ways, depending on the origin and nature of the sensation.
Accelerated Liver Regeneration and Hepatocarcinogenesis in Mice Overexpressing Serine-45 Mutant β-Catenin
Authors: Kari N. Nejak-Bowen, Michael D. Thompson, Sucha Singh, William C. Bowen, Mohd Jamal Dar, Jaspal Khillan, Chunsun Dai, Satdarshan P.S. Monga
Journal: Hepatology (2010)

The Wnt/β-catenin pathway is implicated in the pathogenesis of hepatocellular cancer (HCC). We developed a transgenic mouse (TG) in the FVB strain that overexpresses Ser45-mutated-β-catenin in hepatocytes to study the effects on liver regeneration and cancer. In the two independent TG lines adult mice show elevated β-catenin at hepatocyte membrane with no increase in the Wnt pathway targets cyclin-D1 or glutamine synthetase. However, TG hepatocytes upon culture exhibit a 2-fold increase in thymidine incorporation at day 5 (D5) when compared to hepatocytes from wildtype FVB mice (WT). When subjected to partial hepatectomy (PH), dramatic increases in the number of hepatocytes in S-phase are evident in TG at 40 and WT at 72 hours. Coincident with the earlier onset of proliferation, we observed nuclear translocation of β-catenin along with an increase in total and nuclear cyclin-D1 protein at 40 hours in TG livers. To test if stimulation of β-catenin induces regeneration, we used hydrodynamic delivery of Wnt-1 naked DNA to control mice, which prompted an increase in Wnt-1, β-catenin, and known targets, glutamine synthetase (GS) and cyclin-D1, along with a concomitant increase in cell proliferation. β-Catenin-overexpressing TG mice, when followed up to 12 months, showed no signs of spontaneous tumorigenesis. However, intraperitoneal delivery of diethylnitrosamine (DEN), a known carcinogen, induced HCC at 6 months in TG mice only. Tumors in TG livers showed up-regulation of β-catenin, cyclin-D1, and unique genetic aberrations, whereas other canonical targets were unremarkable. Conclusion: β-Catenin overexpression offers growth advantage during liver regeneration. Also, whereas no spontaneous HCC is evident, β-catenin overexpression makes TG mice susceptible to DEN-induced HCC. Hepatology 2010
The Value of Participation in Research in the Continuing Education of the Practising Doctor
Authors: R. F. Farquharson
Journal: BMJ (1959)

The discovery is usually very modest.Often it is a negative finding, the posting of a warning on a dead- end street.Yet it is a discovery, new knowledge, light into the darkness, a penetration beyond the frontier.Discovery, great or small, of what was never known before is an adventure to be cherished, an experience likely to colour a physician's entire outlook on his work.The physician who is imbued with the spirit of investigation, augmented by research experience, will be a little more persistent in his diagnostic searchings, in his therapeutic efforts, or in his self-evaluation.Summary Experience in research as a medical or graduate student may stimulate a continuation of some investigation throughout life.Even if the physician does no research after his formal education, his earlier experience in investigation will prove of tremendous value, because research sharpens the physician's judgments of the scientific pronouncements of others, it reveals the painful difficulty of discovery, it stimulates the pursuit of a scientific hobby.Research promotes an awareness of unobtrusive " accidental " phenomena which may be of great importance, it provides lessons in team-work, it fosters a respect for persistent routine.Research acquaints the investigator and physician with one of the highways of discovery leading into the unknown.
The Hygiene of Transmissible Diseases: their Causation, Modes of Dissemination and Methods of Prevention.
Authors: A. C. Abbott
Journal: JAMA (1901)

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
Management of Symptomatic Polycystic Liver Disease With Hepatic Resection
Authors: Jennifer Tseng, Susan L. Orloff
Journal: JAMA Surgery (2014)

In conclusion, the preferred approach for patients with severely symptomatic polycystic liver disease with preserved liver and renal function is hepatic resection with drainage, partial liver resection, sclerosis, and marsupialization of the remaining cysts.This safe and feasible strategy helps patients avoid a liver transplant, experience resolution of their symptoms, and have an improved quality of life.Our series of patients experienced long-term success in eradiating symptoms after the majority of them had failed previous, less aggressive surgical options.There were no major complications, no need for reoperation, and no deaths.The use of postoperative long-acting octreotide has the potential to reduce the growth of remaining cysts and prevent new cysts from developing, and it should be considered in the management of these patients after surgery.
Tuberculosis and the Health Care Worker
Authors: David Nicholson
Journal: Annals of Internal Medicine (1994)

Letters1 June 1994Tuberculosis and the Health Care WorkerDavid Nicholson, MDDavid Nicholson, MDUniversity of Arkansas for Medical Sciences; Little Rock, AR 72205Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-11-199406010-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:C.T. Williams of the Brompton Hospital, London, may have averred in 1882 that consumption might not be contagious [1], but shortly thereafter the Board of Governors differed.In the knowledge that diagnosis was imprecise and that many new employees were already infected, the Board provided and paid for a resident's health insurance policy with the Medical Sickness and Annuity Group. One was wise to continue the premiums afterward. Indeed, the Board went further and consolidated our good nutrition by providing each of us with a bottle of stout at dinner. Fortunately, my dinner partner, who was not ...REFERENCE1. Sepkowitz KA. Tuberculosis and the health care worker: a historical perspective. Ann Intern Med. 1993; 120:71-9. Google Scholar Author, Article, and Disclosure InformationAuthors: David Nicholson, MDAffiliations: University of Arkansas for Medical Sciences; Little Rock, AR 72205 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1994Volume 120, Issue 11Page: 971KeywordsHealth care providersHealth insuranceNutrition ePublished: 15 August 2000 Issue Published: 1 June 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Year in review in Intensive Care Medicine 2013: I. Acute kidney injury, ultrasound, hemodynamics, cardiac arrest, transfusion, neurocritical care, and nutrition
Authors: Giuseppe Citerio, Jan Bakker, Matteo Bassetti, Dominique Benoit, Maurizio Cecconi, J. Randall Curtis, Glenn Hernandez, Margaret Herridge, Samir Jaber, Michael Joannidis, Laurent Papazian, Mark Peters, Pierre Singer, Martin Smith, Marcio Soares, Antoni Torres, Antoine Vieillard-Baron, Jean-François Timsit, Elie Azoulay
Journal: Intensive Care Medicine (2013)
Thrombocytopenic Purpura in Narcotics Addicts
Authors: STEVEN SAVONA
Journal: Annals of Internal Medicine (1985)

Since November 1982 we have seen an association of thrombocytopenic purpura with chronic narcotic addiction in 70 patients with a mean platelet count of 53 000 ±4000 (SE); 33 had stopped taking intravenous drugs for an average of 21.2 ±4.7 months; 13 of 15 had elevated antibody titers for a virus related to the acquired immunodeficiency syndrome. Platelet-bound IgG, IgM and complement levels were 16.7-, 5.6-, and 3.1-fold greater than control values, respectively, and 2.6-, 1.9-, and 2.4-fold greater than values in 25 patients with classic autoimmune thrombocytopenic purpura studied at the same time. Thirty-three of thirty-six addicts had elevated circulating immune complexes, whereas 8 patients with autoimmune thrombocytopenia had no elevation. Eleven of eighteen addicts had positive serum platelet-reactive IgG titers, compared to 5 of 19 patients with classic autoimmune thrombocytopenia. The platelet-reactive IgG in sera of addicts was composed of 7S IgG antibody as well as high molecular weight (immune complex) IgG. Thus, chronic addicts appear to have a new immunologic platelet disorder associated with the presence of 7S IgG antiplatelet antibody, like patients with classic autoimmune thrombocytopenic purpura, and immune complex associated nonspecific platelet IgG, like male homosexual patients with thrombocytopenia.
Key Facts in Cardiology
Authors: C. S LAWSON
Journal: Cardiovascular Research (1992)

Journal Article Key Facts in Cardiology Get access CLlVE S LAWSON CLlVE S LAWSON London, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 26, Issue 2, February 1992, Page 190, https://doi.org/10.1093/cvr/26.2.190a Published: 01 February 1992
Carotid Endarterectomy
Authors: Lewis L. Levy
Journal: JAMA (1991)

Many factors influence cerebral circulation in addition to carotid blood flow. The brain accounts for less than 2% of body weight but consumes 20% of the total circulation. Cerebral blood is not transported passively. Rather, complex control systems in the brain vasculature maintain almost constant total cerebral blood flow within a wide range of levels of systemic blood pressure and distribute circulation within the brain unevenly according to local metabolic needs. Signals that originate in pressure sensors in supply arteries initiate changes in systemic blood pressure and adjust resistance in cranial vasculature. These reflexes modify the direction of flow in extracranial arteries. Collateral channels bridge internal to external carotid and vertebral systems. Intracranial arteries link hemispheres, connect carotid and basilar artery territories, and—on the brain surface—join branches of middle cerebral, anterior cerebral, and posterior cerebral arteries. Within these vascular territories, blood flow is coupled to local brain metabolism. Parenchymal arteriolar
Vasopressin potentiates mineralocorticoid selectivity by stimulating 11 beta hydroxysteroid deshydrogenase in rat collecting duct.
Authors: N Alfaidy, M Blot-Chabaud, J P Bonvalet, N Farman
Journal: Journal of Clinical Investigation (1997)

Arginine vasopressin (AVP) and corticosteroid hormones are involved in sodium reabsorption regulation in the renal collecting duct. Synergy between AVP and aldosterone has been well documented, although its mechanism remains unclear. Both aldosterone and glucocorticoid hormones bind to the mineralocorticoid receptor (MR), and mineralocorticoid selectivity depends on the MR-protecting enzyme 11 beta hydroxysteroid deshydrogenase (11-HSD), which metabolizes glucocorticoids into derivatives with low affinity for MR. We have investigated whether the activity of 11-HSD could be influenced by AVP and corticosteroid hormones. This study shows that in isolated rat renal collecting ducts, AVP increases 11-HSD catalytic activity. This effect is maximal at 10(-8) M AVP (a concentration clearly above the normal physiological range of AVP concentrations) and involves the V2 receptor pathway, while activation of protein kinase C or changes in intracellular calcium are ineffective. The stimulatory effect of AVP on 11-HSD is largely reduced after adrenalectomy, and is selectively restored by infusion of aldosterone, not glucocorticoids. We conclude that this synergy between AVP and aldosterone in controlling the activity of 11-HSD is likely to play a pivotal role in resetting mineralocorticoid selectivity, and hence sodium reabsorption capacities of the renal collecting duct.
Hypertension and Borderline Isolated Systolic Hypertension Increase Risks of Cardiovascular Disease and Mortality in Male Physicians
Authors: Christopher J. O'Donnell, Paul M. Ridker, Robert J. Glynn, Klaus Berger, Umed Ajani, JoAnn E. Manson, Charles H. Hennekens
Journal: Circulation (1997)

Background The objective of this study was to examine whether definite hypertension and borderline isolated systolic hypertension predict subsequent cardiovascular disease and mortality. Methods and Results This was a prospective cohort study with a mean follow-up of 11.7 years. The subjects were a group of 18 682 apparently healthy US men, aged 40 to 84 years, participating in the Physicians' Health Study, a randomized trial of low-dose aspirin and β-carotene. The main outcome measures were total cardiovascular disease, myocardial infarction, stroke, cardiovascular death, and all-cause mortality. Hypertension was associated with substantially increased risks of total cardiovascular disease (relative risk [RR] 1.92; 95% confidence interval [CI], 1.70 to 2.18), myocardial infarction (RR, 1.78; 95% CI, 1.49 to 2.13), stroke (RR, 2.19; 95% CI, 1.78 to 2.69), and cardiovascular death (RR, 2.10; 95% CI, 1.68 to 2.63). Borderline isolated systolic hypertension was associated with significantly increased risks of cardiovascular disease (RR, 1.32; 95% CI, 1.09 to 1.59), stroke (RR, 1.42; 95% CI, 1.04 to 1.93), and cardiovascular death (RR, 1.56; 95% CI, 1.13 to 2.15), as well as a possible but nonsignificant increased risk of myocardial infarction (RR, 1.26; 95% CI, 0.95 to 1.67). Hypertension and borderline isolated systolic hypertension were associated with significantly increased risks of 41% and 22%, respectively, for all-cause mortality. Conclusions Hypertension as well as borderline isolated systolic hypertension are associated with elevated risks of cardiovascular diseases, especially stroke and cardiovascular death. Hypertension is associated with an increased risk of myocardial infarction, and borderline isolated systolic hypertension predicts a possible but more modest increase in risk. These data add to the existing evidence that hypertension is a major cardiovascular risk factor and extend the findings to borderline isolated systolic hypertension.
Funding for Patient-Oriented Research
Authors: Gordon H. Williams
Journal: JAMA (1997)

<h3>Context.</h3> —Interest in clinical investigative careers has declined over the past 2 decades. While several factors are likely involved in this decline, one is the perceived difficulty in obtaining support for investigator-initiated clinical research projects. <h3>Objective.</h3> —To analyze the priority scores and funding rates of patient-oriented research (POR) compared with laboratory-oriented research (LOR) when grant applications to the National Institutes of Health (NIH) are reviewed by study sections of the NIH Division of Research Grants. <h3>Design.</h3> —Research grant applications submitted to NIH were classified by the applicant as involving human subjects or not (LOR). Those classified as involving human subjects were divided into clinical (POR) and nonclinical research. The association of priority score and POR or LOR status was evaluated using ϰ<sup>2</sup>statistical techniques. <h3>Setting and Participants.</h3> —Twelve thousand investigator-initiated grant applications (RO1s) in 2 of the 1994 NIH review cycles. <h3>Main Outcome measures.</h3> —Grant application priority scores and funding rates. <h3>Results.</h3> —On the basis of the following 3 criteria, POR applications fare less well than LOR applications: (1) POR status and ranking in the total application pool; (2) percentage of POR vs LOR applications in the top 20th percentile; and (3) funding rates of POR applications. Furthermore, the fate of a POR application depended on which study section reviewed the application. Those applications that were reviewed in study sections that primarily reviewed POR applications fared equivalently to LOR applications; in contrast, POR applications reviewed in study sections that primarily reviewed LOR applications encountered a less favorable fate. <h3>Conclusions.</h3> —These objective data provide strong support to the clinical research community's concern that investigator-initiated POR applications are not reviewed equitably at the NIH. By restructuring the review process, fairness is likely to be restored. Without restructuring, the POR component of the medical research community may be critically damaged.
Electrocardiographic Leads
Authors: RICHARD MCFEE, FRANKLIN D. JOHNSTON
Journal: Circulation (1954)

This concluding paper of a series of three on electrocardiographic leads indicates how leads that should be superior to many now in use may be constructed. The design of leads to obtain accurate representations of the mean cardiac vector in the usual planes of reference, methods for the improvement of several of the conventional leads, and a unipolar lead of a new type are emphasized.