tbuckley/cabot-search huggingface dataset:
OT2-04-01: A Randomized Phase II Trial of Vitamin D vs Placebo in Premenopausal Women: CALGB 70806.
Authors: ME Wood, F Kingsley, AB Ambaye, L Yee, S-H Jung, JR Marshall, E Paskett
Journal: Cancer Research (2011)

Abstract Background Chemoprevention studies are long and expensive. Gaining information about the feasibility of an agent using biomarker endpoints can save money and ensure that only the most promising agents move forward. There is strong evidence to suggest breast cancer prevention properties for vitamin D. The safety and tolerability of this agent makes it a perfect candidate for a chemopreventive agent. This clinical trial will evaluate the effect of vitamin d on several breast cancer; providing important information regarding the feasibility of a larger chemoprevention study using cancer development as the endpoint. Successful completion of this study will also validate this design of biomarker testing of potential chemoprevention agents within a cooperative group setting and add to data validating these specific biomarkers. Methods: This is a randomized placebo controlled trial of one year of 2000 units of vitamin D (cholecalciferol) for premenopausal women (≥ 35 years) with increased breast density. The primary aim of this study is to evaluate the effect of vitamin D on breast density. Secondary aims include evaluation of vitamin D effects on IGF1 and markers of cellular proliferation (Ki-67 and atypia). In addition 3 methods of density analysis (Breast Imaging Reporting and Data System (BI-RADS), Visual Analogue Scale (VAS), and the Boyd method) will be compared. For the primary endpoint of change in mammographic density we will have an 87% power to detect a standardized effect size (difference in means divided by standard deviation) of 0.4 in change of mammographic density between two arms. The target effect size is 2.64%.This study was activated 10/15/2010 and has been opened at 75 sites with 15 patients enrolled. Target accrual is 250. Funding: This study is sponsored by the NCI and CALGB. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-04-01.
A2.16 Inhibition of lymphocyte activation in primary Sjögren syndrome (PSS)
Authors: N Legány, G Toldi, N Megyes, C Orbán, L Kovács, A Balog
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> Primary Sjögren's syndrome (pSS) is an autoimmune diseases characterised by ocular and oral dryness due to the progressive destruction of lachrymal and salivary glands by an inflammatory process. The short-term activation of peripheral blood and exocrin glands T lymphocytes plays a crucial role in initiating and maintaining the chronic inflammation. The transient increase of the cytoplasmic free calcium level plays a key role in the process of lymphocyte activation. Kv1.3 and IKCa1 potassium channels are important regulators of the maintenance of calcium influx during lymphocyte activation. The influx of calcium is maintained by the function of potassium channels that conserve the electrochemical potential gradient via the efflux of potassium from the cytoplasm. Recent reports raised the notion that the inhibition of lymphocyte potassium channels, especially that of the Kv1.3 channel would be an optimal solution for specific immunosuppression in autoimmune disorders. Therefore, in this study we aimed to characterise the effects of lymphocyte potassium channel inhibition on short-term peripheral blood T lymphocyte activation in major lymphocyte subsets in pSS. <h3>Methods</h3> We enrolled 8 healthy individuals and 15 pSS patients. We evaluated calcium influx kinetics following activation in CD4, Th1, Th2 and CD8 cells applying a novel flow cytometry approach. We assessed the sensitivity of the above subsets to specific inhibition of the Kv1.3 and IKCa1 potassium channels. We also assessed the Kv1.3 expression on lymphocytes. <h3>Results</h3> The peak of calcium influx in lymphocytes isolated from pSS patients is reached later, indicating that they respond more slowly to stimulation compared to controls. In healthy individuals, the inhibition of the IKCa1 channel decreased calcium influx in Th2 and CD4 cells to a lower extent than in Th1 and CD8 cells. On the contrary, the inhibition of Kv1.3 channels resulted in a larger decrease of calcium entry in Th2 and CD4 than in Th1 and CD8 cells. Neither the inhibition of IKCa1 channel nor the inhibition of Kv1.3 channels has an influence on intracellular calcium kinetic in pSS. The expression of Kv1.3 channels on CD4, Th2 and CD8 lymphocytes was significantly higher compared to controls. <h3>Conclusion</h3> There is an alteration of the short-term activation of peripheral lymphocytes in pSS. The inhibition of Kv1.3 and IKCa1 channels does not seem to be specific enough in peripheral pSS lymphocytes. The overexpression of Kv1.3 channels in pSS might be a compensatory mechanism of the dysfunction of Kv1.3 and IKCa1 channels, theoretically.
Tolbutamide and Truth
Authors: ARTHUR CHERNOFF
Journal: Annals of Internal Medicine (1971)

Letters, Comments, and Corrections1 November 1971Tolbutamide and TruthARTHUR CHERNOFFARTHUR CHERNOFFSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-75-5-807_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Dr. Schwartz's article on the tolbutamide controversy (ANNALS75:303-306, 1971) is revealing in its presentation of the moral dilemmas that face the physician-researcher. After analyzing the methods of the UGDP study, as well as the madness of its critics, he asks the reader to consider that neither the pitfalls in the study nor the rhetorical skills of its opponents could "erase the impact of what is reproduced in Figure 1." This figure shows that the cumulative mortality rate in the tolbutamide therapy group was the greatest of all groups in the study. Dr. Schwartz states that after... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1971Volume 75, Issue 5Page: 807-807KeywordsDeath rates Issue Published: 1 November 1971 PDF DownloadLoading ...
Early Revascularization in Acute Myocardial Infarction Complicated by Cardiogenic Shock
Authors: Judith S. Hochman, Lynn A. Sleeper, John G. Webb, Timothy A. Sanborn, Harvey D. White, J. David Talley, Christopher E. Buller, Alice K. Jacobs, James N. Slater, Jacques Col, Sonja M. McKinlay, Michael H. Picard, Mark A. Menegus, Jean Boland, Vladimir Dzavik, Christopher R. Thompson, S. Chiu Wong, Richard Steingart, Robert Forman, Philip E. Aylward, Emilie Godfrey, Patrice Desvigne-Nickens, Thierry H. LeJemtel
Journal: New England Journal of Medicine (1999)

The leading cause of death in patients hospitalized for acute myocardial infarction is cardiogenic shock. We conducted a randomized trial to evaluate early revascularization in patients with cardiogenic shock.
Endogenous Sex Hormones and Type 2 Diabetes Risk—Reply
Authors: Eric L. Ding, Yiqing Song, Simin Liu
Journal: JAMA (2006)

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
THE IMPACT OF OXYGEN TENSION ON CD8+ T CELL FUNCTION AND INTERACTION WITH GLIOMA CELLS
Authors: P. R. Walker, R. V. de Silly, M. Derouazi
Journal: Neuro-Oncology (2014)

BACKGROUND: (blind field) METHODS: We studied a clonal population of gp100 antigen-specific CD8+ T cells from pmel-1 mice and the assays were performed in vitro in a hypoxia work station. 5% O2 corresponds to the expected oxygen fraction in lymph nodes where most T cells are physiologically primed. Interactions with glioma were modelled using gp100-expressing GL261 glioma cells. RESULTS: In vitro activation of CD8+ T cells at physiologic O2 fraction generated cytotoxic T cells (CTLs) with higher effector functions (cytotoxicity and IFN-γ secretion) than at the 21% used in conventional culture. After activating CD8+ T cells at different O2 fractions, we then studied their function under hypoxia (1% O2), mimicking conditions after migration and infiltration of the glioma. Co-culture of CTLs and GL261 glioma cells at 1% O2 resulted in efficient tumor cell lysis, indicating that in the short term, hypoxia does not inhibit the killing capacities of CTLs, and that glioma cells are susceptible to immune-mediated elimination in this microenvironment. However, we also measured negative effects of hypoxia on anti-tumour immunity: CTL secretion of the immunosuppressive cytokine IL-10 and reduced T cell proliferation. CONCLUSIONS: Overall, these results validate the potential of T cell-based glioma therapy, even for glioma cells in hypoxic regions of the tumor. However, if sustained T cell responses are required for clinical efficacy, local amplification of anti-glioma effector cells may be limited by oxygen availability in the microenvironment, with the risk of accumulation of the immunosuppressive cytokine IL-10. SECONDARY CATEGORY: n/a.
Trimethoprim-Sulfamethoxazole or Pentamidine for Pneumocystis Pneumonia in the Acquired Immunodeficiency Syndrome
Authors: TERRY DENNIS
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 October 1986Trimethoprim-Sulfamethoxazole or Pentamidine for Pneumocystis Pneumonia in the Acquired Immunodeficiency SyndromeTERRY DENNIS, M.D.TERRY DENNIS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-105-4-629_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The report by Wharton and colleagues (1) in the July issue on the use of trimethoprim-sulfomethoxazole or pentamidine for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS) was a valuable addition to the knowledge on treatment of this disorder. Although the trial appears to have been well designed, I believe the results (20% mortality in the trimethoprim-sulfamethoxazole group compared with 5% in the pentamidine group) are too easily discounted by the authors.The ñ value of 0.09 did not attain the alpha = 0.05 level; however, when the mortality rate is...References1. WHARTONCOLEMANWOFSY JDC. Trimethoprim-sulfamethoxazole or pentamidine for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome: a prospective randomized trial. Ann Intern Med. 1986;105:37-44. LinkGoogle Scholar2. LEOUNGMILLSHOPEWELLHUGHESWOFSY GJPWC. Dapronetrimethoprim for Pneumocystis carinii pneunonia in the acquired immunodeficiency syndrome. Ann Intern Med. 1986;105:45-8. LinkGoogle Scholar1. WHARTONCOLEMANWOFSY JDC. Trimethoprim-sulfamethoxazole or pentamidine for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome: a prospective randomized trial. Ann Intern Med. 1986;105:37-44. LinkGoogle Scholar2. SACKETTGENT DM. Controversy in counting and attributing events in clinical trials. N Engl J Med. 1979;301:1410-2. CrossrefMedlineGoogle Scholar3. REMINGTONSCHORK RM. Statistics, with Applications to the Biological and Health Sciences. 2nd ed. Englewood Cliffs, New Jersey: Prentice-Hall; 1985:192-4. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByTreatment of Pneumocystis jirovecii pneumonia in HIV-infected patients: a reviewPneumocystis Jiroveci (Pneumocystis Carinii) InfectionsSilence, Death, and the Invisible Enemy: AIDS Activism and Social Movement "Newness"Management of Pneumocystis carinii Pneumonia in Patients with AIDS and Other Conditions: Experience in a Philadelphia University Teaching HospitalTrimethoprim-Sulfamethoxazole or Pentamidine for Pneumocystis carinii PneumoniaPAUL BÉGIN, M.D., JAMES HANLEY, Ph.D. 1 October 1986Volume 105, Issue 4Page: 629-630KeywordsAIDSDeath ratesMortalityPneumocystisPneumocystis carinii pneumoniaPneumonia Issue Published: 1 October 1986 PDF DownloadLoading ...
Peripheral mononuclear leucocyte beta adrenoceptors and non-specific bronchial responsiveness to methacholine in young and elderly normal subjects and asthmatic patients.
Authors: M J Connolly, J J Crowley, C P Nielson, N B Charan, R E Vestal
Journal: Thorax (1994)

BACKGROUND--As beta adrenoceptor dysfunction occurs in both the normal elderly subject and in young asthmatic patients, the hypothesis was examined that age related beta adrenoceptor changes are important in the pathogenesis of late onset asthma in old age. METHODS--Subjects were non-smokers who comprised 17 young normal subjects of mean (SE) age 29.4 (1.3) years, 17 elderly normal subjects of 67.2 (1.3) years, seven young asthmatic patients of 31.0 (2.8) years, and 17 elderly asthmatic patients of 68.5 (1.4) years. All asthmatic patients withheld inhalers for 12 hours and oral treatment for 24 hours before each study day. Subjects underwent an inhaled methacholine challenge (Newcastle dosimeter method) on two nonconsecutive days. The slope of the flow at 50% of the vital capacity (FEF50) dose-response curve was derived from the percentage fall in FEE50 divided by methacholine dose (sFEF50). Beta-adrenoceptor density (Bmax) and affinity (%KH) were determined with (125I)iodocyanopindolol as the radioligand in membranes prepared from mononuclear leucocytes. RESULTS--Log sFEF50 was shown to be reproducible (repeatability coefficient 0.41) on the two study days and was inversely related to %KH but not to Bmax. Multiple regression analysis (all 58 subjects, overall R2 = 0.57) revealed an inverse relation between log sFEF50 and %KH, and between log sFEF50 and Bmax. The inverse relation between log sFEF50 and %KH was preserved whereas that between log sFEF50 and Bmax was lost when young asthmatic subjects or when all asthmatic subjects were excluded from multiple regression analysis. CONCLUSIONS--The beta adrenoceptor dysfunction observed in late onset asthma may be similar to that seen during ageing. Thus late onset asthma may represent the extreme of a spectrum of age associated beta adrenoceptor dysfunction.
Liver-specific deletion of prohibitin 1 results in spontaneous liver injury, fibrosis, and hepatocellular carcinoma in mice
Authors: Kwang Suk Ko, Maria Lauda Tomasi, Ainhoa Iglesias-Ara, Barbara A. French, Samuel W. French, Komal Ramani, Juan José Lozano, Pilsoo Oh, Lina He, Bangyan L Stiles, Tony W.H Li, Heping Yang, M. Luz Martínez-Chantar, José M. Mato, Shelly C. Lu
Journal: Hepatology (2010)

Prohibitin 1 (PHB1) is a highly conserved, ubiquitously expressed protein that participates in diverse processes including mitochondrial chaperone, growth and apoptosis. The role of PHB1 in vivo is unclear and whether it is a tumor suppressor is controversial. Mice lacking methionine adenosyltransferase 1A (MAT1A) have reduced PHB1 expression, impaired mitochondrial function, and spontaneously develop hepatocellular carcinoma (HCC). To see if reduced PHB1 expression contributes to the Mat1a knockout (KO) phenotype, we generated liver-specific Phb1 KO mice. Expression was determined at the messenger RNA and protein levels. PHB1 expression in cells was varied by small interfering RNA or overexpression. At 3 weeks, KO mice exhibit biochemical and histologic liver injury. Immunohistochemistry revealed apoptosis, proliferation, oxidative stress, fibrosis, bile duct epithelial metaplasia, hepatocyte dysplasia, and increased staining for stem cell and preneoplastic markers. Mitochondria are swollen and many have no discernible cristae. Differential gene expression revealed that genes associated with proliferation, malignant transformation, and liver fibrosis are highly up-regulated. From 20 weeks on, KO mice have multiple liver nodules and from 35 to 46 weeks, 38% have multifocal HCC. PHB1 protein levels were higher in normal human hepatocytes compared to human HCC cell lines Huh-7 and HepG2. Knockdown of PHB1 in murine nontransformed AML12 cells (normal mouse hepatocyte cell line) raised cyclin D1 expression, increased E2F transcription factor binding to cyclin D1 promoter, and proliferation. The opposite occurred with PHB1 overexpression. Knockdown or overexpression of PHB1 in Huh-7 cells did not affect proliferation significantly or sensitize cells to sorafenib-induced apoptosis.Hepatocyte-specific PHB1 deficiency results in marked liver injury, oxidative stress, and fibrosis with development of HCC by 8 months. These results support PHB1 as a tumor suppressor in hepatocytes.
Case 20-1978
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Roman W. DeSanctis, John T. Fallon
Journal: New England Journal of Medicine (1978)

Presentation of CaseA 58-year-old man was admitted to the hospital because of dyspnea and anasarca.He was well until eight years previously, when an enlarged right cervical lymph node was found. Examination was otherwise negative. An x-ray film of the chest (Fig. 1) demonstrated widening of the right superior mediastinum and slight elevation of the right hemidiaphragm. An intravenous pyelographic examination showed calcified mesenteric lymph nodes; the spleen appeared slightly enlarged; the right kidney was normal in size and configuration; a rounded mass, 8 cm in diameter, projected from the lower pole of the left kidney and distorted the . . .
Coronary vasospasm and sumatriptan.
Authors: B. H. Stricker
Journal: BMJ (1992)

metal's angina are both given as contraindications in the datasheet for sumatriptan; the datasheet also includes advice against the concomitant use of ergotamine.Willett and colleagues' report there- fore clearly highlights the need for these warnings and emphasises that sumatriptan should be avoided if there is a history of ischaemic heart disease or undiagnosed chest pain.
Metastatic Basal Cell Carcinoma in Acquired Immunodeficiency Syndrome—Related Complex
Authors: Karl V. Sitz
Journal: JAMA (1987)

Basal cell carcinoma is a common neoplasm that rarely metastasizes. Metastatic basal cell carcinoma has been associated with a deficiency of cellular immunity. Patients with acquired immunodeficiency syndrome, at greater risk for specific neoplasms, may be at greater risk for basal cell carcinoma and subsequent metastasis. We report a case of metastatic basal cell carcinoma in a patient with acquired immunodeficiency syndrome-related complex.
Surgical treatment of infective endocarditis with special reference to prosthetic valve endocarditis.
Authors: S Westaby, C Oakley, R N Sapsford, H H Bentall
Journal: BMJ (1983)

Patients with native valve endocarditis treated surgically between 1968 and 1978 (n = 15) and all patients presenting with prosthetic valve endocarditis during this period (n = 21) were followed up for at least four years. Five of the patients with native valve endocarditis required urgent early surgical intervention, of whom two died. The remaining 10 underwent valve replacement after a course of antibiotic treatment: all survived, though one required further valve replacement. The 21 patients with prosthetic valve endocarditis suffered 25 attacks. Nine were cured by medical treatment alone; two died before surgical intervention was possible; 11 required valve replacement, of whom three died; and two required valve replacement after a course of antibiotic treatment. The incidence of early prosthetic valve endocarditis--that occurring within two months of operation--was 0.67%, but that of late prosthetic valve endocarditis could not be determined. Medical treatment when started early should cure endocarditis in most patients, but vigilance should be maintained for the appearance of indications for surgery. When such indications exist surgery should not be delayed.
Arginine Vasopressin Levels Are Elevated and Correlate With Functional Status in Infants and Children With Congestive Heart Failure
Authors: Jack F. Price, Jeffrey A. Towbin, Susan W. Denfield, Sarah Clunie, E.O. Smith, Colin J. McMahon, Branislav Radovancevic, William J. Dreyer
Journal: Circulation (2004)

Arginine vasopressin (AVP) is a vasoactive hormone that acts on the kidney to conserve solute-free water and produces a potent vasoconstrictive effect during hypovolemic states. AVP levels are elevated in adults with congestive heart failure (CHF), and early clinical trials using AVP antagonists are being conducted. The purpose of this study was to determine if AVP levels (1) are elevated in children with CHF attributable to left ventricular dysfunction or pulmonary overcirculation attributable to large left-to-right shunts and (2) can predict functional clinical status.AVP levels were measured in patients with dilated cardiomyopathy (DCM) and CHF and in patients with large left-to-right intracardiac shunts. Each patient with DCM (ejection fraction percent <40%) was classified as NYHA functional class I through IV when the AVP level was drawn. Serum sodium was measured, serum osmolality was calculated, and echocardiograms and chest radiographs were performed on all study patients. AVP levels were also measured in age-matched controls. Mean AVP level in children with DCM (n=27) was 10.3 pg/mL (+/-12.8) versus 3.7 pg/mL (+/-2.4) in controls (n=15) (P<0.01). Mean AVP level in children with left-to-right shunts (n=14) was 13.9 pg/mL (+/-17.3) versus 3.5 pg/mL (+/-1.3) in controls (n=8) (P<0.04). In patients with DCM, AVP levels correlated directly with NYHA functional class (r2=0.73, P<0.001).Arginine vasopressin levels are elevated in infants and children with CHF attributable to left ventricular dysfunction and in infants with large left-to-right intracardiac shunts. Furthermore, there is a direct relationship between AVP level and the severity of heart failure in patients with DCM.
Long-Term Survival in Two Cases of Resected Gastric Metastasis of Pulmonary Pleomorphic Carcinoma
Authors: Keiju Aokage, Junji Yoshida, Genichiro Ishii, Shinichiro Takahashi, Masanori Sugito, Mitsuyo Nishimura, Atsushi Ochiai, Kanji Nagai
Journal: Journal of Thoracic Oncology (2008)