tbuckley/cabot-search huggingface dataset:
Editorial: Nostalgia: a vanished disease.
Journal: BMJ (1976)

acute exacerbations of SLE.Comparisons of cyclophosphamide, azathioprine, and placebo have also been made in lupus nephritis.7 8 Cyclophosphamide was found to have a more beneficial effect on urine sediment, proteinuria, and serum complement in one study7 and produced symptomatic improvement and a fall in DNA antibody titre in the other.8Recently the results of two larger trials using these agents in SLE have been published9 10 in which the benefits produced were marginal.Hahn and her colleagues9 carried out a prospective randomised trial comparing prednisone (60 mg per day initially) to prednisone plus azathioprine (3-4 mg/kg body weight per day) in 24 patients with life-threatening SLE.During a mean follow-up period of 18-24 months there were no significant differences in outcome as assessed by the number of deaths, renal and extrarenal manifestations, serum complement levels, and DNA antibodies.There was no convincing evidence of a steroid-sparing effect of azathioprine.In the second study, cyclophosphamide or azathioprine was added to low-dose corticosteroid therapy in 38 patients with diffuse lupus glomerulonephritis.The cytotoxic agents added only marginally to the control of the disease, though it was noted that no SLE-related death, renal or otherwise, occurred among the 12 patients treated with cyclophosphamide.10These important studies throw doubt on the value of immunosuppressive drugs in SLE, but it might be said that the patients were at the severe end of the disease spectrum.In most patients SLE may be a mild disease with a reasonable prognosis,11 and it is among these patients that any potential therapeutic effect of immunosuppressive agents requires critical analysis.The long-term risk of malignancy, especially in a disease in which immunodeficiency may play an aetiological part,'2 must be high, and the case for therapeutic conservatism is strong.When nephritis is established powerful alternatives to corticosteroids are still required; unfortunately the case for immunosuppressives, on present evidence, remains unproved.
Harrower's Monographs on the Internal Secretions. Hyperthyroidism: Medical Aspects.
Journal: JAMA (1921)

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
P08.40 The prognostic and predictive value of an explant assay of gliomas in response to temozolomide
Authors: J. F. Megyesi, A. Wolf, W. MacDonald, D. R. Macdonald, P. Costello
Journal: Neuro-Oncology (2017)

Introduction: Glioblastoma multiforme (GBM) is the most common and lethal primary adult brain tumor, with significant variability in therapeutic response due to its underlying molecular and pathological heterogeneity. This study investigated the prognostic and predictive value of an established explant assay in response to the clinically relevant chemotherapy temozolomide (TMZ). METHODS: 138 patients with pathologically-verified gliomas and ongoing follow-up of clinical outcomes were included in the study. Tumor specimens at the time of resection were plated onto a collagen matrix with and without TMZ. Using photo-microscopy, the migratory distance of invading cells was quantified over 5 days. Results: 111 viable and malignant explant assays were collected in glioma patients with overall survival outcomes available on 80% of them. GBMs showed increased invasiveness compared to anaplastic and grade II gliomas on the assay. Glioma patients whose tumors showed a greater invasive distance on the assay at 5 days had reduced overall survival. Inhibition of invasion by 20% by TMZ on the explant assay predicted the time to recurrence after TMZ treatment and the overall survival of GBM patients. Response in this assay was compared to additional parameters including induction of apoptosis and MGMT methylation status. There was a correlation of 75% with TMZ sensitivity and MGMT methylation. Apoptosis marker caspase was increased in TMZ sensitive tumours by 15 % over non-treated control tumours when examined post-treatment. This increase in caspase was only 5% in non-sensitive tumors. CONCLUSION: This study demonstrates that an explant assay, by reproducing the in vivo environment, can predict overall survival of gliomas patients and response to temozolomide. This study demonstrates that this assay is of individualized prognostic value.
Abstracts
Journal: Annals of the Rheumatic Diseases (1952)

At the end of each section is a list of titles of articles noted but not abstracted.Not all sections may be represented in any one issue.The section " ACTH, Cortisone, and other Steroids " includes abstracts and titles of articles dealing with steroid research, which, although not directly concerned with the rheumatic diseases, may make an important contribution to knowledge of the scope and modus operandi of steroid therapy. Acute RheumatismRheumatic Fever in Young Adults.ZIMDAHL, W. T. (1952).Brit.Hearf J
Biomarker Research in Neurotoxicology: The Role of Mechanistic Studies to Bridge the Gap between the Laboratory and Epidemiological Investigations
Authors: Lucio G. Costa
Journal: Environmental Health Perspectives (1996)

There is an increasing interest in the development and validation of biomarkers for use in biochemical/molecular epidemiological studies.Though the area of neurotoxicology has received much attention in the past several years, it still lags behind with regard to the development of biomarkers, particularly those of health effects and susceptibility.This review discusses several aspects of biomarker research as it relates to neurotoxic compounds and focuses on selected agents (organophosphorus insecticides, styrene, n-hexane, carbon disulfide, acrylamide), which have been the subject of a number of investigations in animals and humans.While traditional biomonitoring approaches and novel techniques (e.g., hemoglobin adducts) provide several measurements for monitoring exposure to neurotoxic chemicals, potential markers of genetic susceptibility have been seldom investigated in a neurotoxicology context.Furthermore, the complexity of the nervous system, together with the multiplicity of end points and the limited knowledge of the exact mechanism(s) of action of neurotoxicants, has led to only limited advancements in the development of biomarkers for neurotoxic effects.Significant progress in this area will depend upon an increased understanding of the cellular, biochemical, and molecular targets directly involved in neurotoxicity.Environ Health Perspect 1 04(Suppl 1): 55-67 (1996)
THE PERIODICITY OF DREAMS.
Journal: JAMA (1905)

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
Genetic Screening by Insurance Carriers
Authors: Alan L. Engelberg
Journal: JAMA (1992)

<h3>To the Editor.</h3> —The article by the American Medical Association's Council on Ethical and Judical Affairs on genetic testing by employers<sup>1</sup>and the accompanying article by Dr Juengst<sup>2</sup>raise important issues about the use of medical testing for decisions about employment. It is gratifying to see that both articles stress the value of the Americans With Disabilities Act (ADA) in protecting individuals against adverse employment decisions based on an unwarranted use of and interpretation of medical information. However, both articles barely make mention of a glaring loophole in the ADA through which the results of genetic testing, or any other medical information unrelated to job assignment, will fall: the ADA does not prohibit insurance companies from denying health insurance coverage to individuals for "preexisting" conditions.<sup>3</sup>To underscore that point, the report of the House of Representatives committee that drafted the Act states: "[W]ith respect to group health
Health is poorer in US states with larger income inequalities
Journal: BMJ (1998)

No clustering of anophthalmia occurs in England, but prevalence is higher in rural areas On p 905 Dolk et al describe a study set up to answer public concern after media allegations that clusters of babies were born with anophthalmia and microphthalmia in England and a link with pesticide exposure postulated.The results suggest little localised geographical clustering in babies born in 1988-94.However, the condition is more prevalent in rural areas and this observation requires confirmation and investigation.
ORIENTALISM.
Journal: JAMA (1906)

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
Protein kinase Cδ amplifies ceramide formation via mitochondrial signaling in prostate cancer cells
Authors: Makoto Sumitomo, Motoi Ohba, Junichi Asakuma, Takako Asano, Toshio Kuroki, Tomohiko Asano, Masamichi Hayakawa
Journal: Journal of Clinical Investigation (2002)

We studied the role of protein kinase C isoform PKCδ in ceramide (Cer) formation, as well as in the mitochondrial apoptosis pathway induced by anticancer drugs in prostate cancer (PC) cells. Etoposide and paclitaxel induced Cer formation and apoptosis in PKCδ-positive LNCaP and DU145 cells but not in PKCδ-negative LN-TPA or PC-3 cells. In contrast, these drugs induced mitotic cell cycle arrest in all PC cell lines. Treatment with Rottlerin, a specific PKCδ inhibitor, significantly inhibited drug-induced Cer formation and apoptosis in LNCaP cells, as did overexpression of dominant negative–type PKCδ. Overexpression of wild-type PKCδ had an opposite effect in PC-3 cells. Notably, etoposide induced biphasic Cer formation in LNCaP cells. The early and transient Cer increase resulted from de novo Cer synthesis, while the late and sustained Cer accumulation was derived from sphingomyelin hydrolysis by neutral sphingomyelinase (nSMase). Cer, in turn, induced mitochondrial translocation of PKCδ and stimulated the activity of this kinase, promoting cytochrome c release and caspase-9 activation. Furthermore, the specific caspase-9 inhibitor LEHD-fmk significantly inhibited etoposide-induced nSMase activation, Cer accumulation, and PKCδ mitochondrial translocation. These results indicate that PKCδ plays a crucial role in activating anticancer drug–induced apoptosis signaling by amplifying the Cer-mediated mitochondrial amplification loop.
Esophageal Angina
Authors: John T. Larkin
Journal: JAMA (1983)

<h3>To the Editor.—</h3> The article on esophageal angina was timely. This variant of esophageal disease has received too little attention in the literature. Many physicians, especially those engaged in an active emergency service, are well aware of this condition. After retirement from general practice, I spent five years with an active metropolitan emergency room group. When a patient had severe chest pain that was not of evident cardiac origin, he was given an immediate dose of liquid antacid orally. In esophageal angina, the relief was immediate. On further questioning, a number of these patients gave a history of recurrent pyrosis. After cardiac studies were completed, these patients were usually discharged from the hospital with an antacid prescription and urged to see their physician for further evaluation of their conditions. In the article inThe Journal, therapy was not discussed. I presume that antacids and other appropriate measures were used. The
Influenza Activity—United States, 2000-01 Season
Journal: JAMA (2001)

1 Influenza activity was low to moderate but increasing in the United States.Since October 1, the most frequently isolated viruses were influenza A (H1N1) and were well matched antigenically with the 2000-01 influenza A (H1N1) vaccine strain.During October 1, 2000-January 13, 2001, World Health Organization collaborating laboratories and National Respiratory and Enteric Virus Surveillance System laboratories in the United States tested 26,789 specimens for influenza: 1545 (6%) were positive.Of these, 1132 (73%) were influenza A and 413 (27%) were influenza B. Of the 1132 influenza A isolates collected, 457 (40%) have been subtyped: 441 (96%) were A (H1N1) and 16 (4%) were A (H3N2).Of the 56 influenza A (H1N1) isolates characterized antigenically at CDC, 53 (95%) were A/New Caledonia/ 20/99-like (H1N1) viruses, the H1N1 component of the 2000-01 vaccine strain, and three (5%) were A/Bayern/ 07/95-like (H1N1) viruses.The A/New Caledonia/20/99 vaccine strain produces high titers of antibody that are cross-reactive to A/Bayern/07/95-like (H1N1) viruses. 2 Ten influenza A (H3N2) viruses and 20 influenza B viruses were characterized; all were similar antigenically to vaccine strains A/Panama/2007/99 (H3N2) and B/Beijing/184/93, respectively.The percentage of positive influenza infections, an important indicator of influenza activity, increased from 4% during the week ending November 25 to 15% during the week ending January 13.During November 6, 2000-January 13, 2001, 2%-3% of patient visits to U.S. sentinel physicians were for influenzalike illness (ILI).* During the week ending January 13 (week 2), patient visits for ILI were at baseline levels (0-3%) in seven of nine surveillance regions.Levels were above baseline in the Pacific (6%) and West South Central (4%) regions.During the same week, widespread † influenza activity was reported in Rhode Island and Virginia, and regional activity was reported in 21 states (Alabama, Arizona, Colorado, Connecticut, Idaho, Iowa, Kansas, Kentucky, Louisiana, Maryland, Massachusetts, Minnesota, Mississippi, Nevada, North Carolina, Oregon, Tennessee, Texas, Utah, Washington, and Wyoming); 26 states reported sporadic activity, and one state did not report.The 122 Cities Mortality Reporting System attributed 7.7% of recorded deaths to pneumonia and influenza (P&I).This percentage was below the epidemic threshold ‡ of 8.5% for week 2. The percentage of P&I deaths has remained below the epidemic threshold for each week since October 1.
Rheumatology
Authors: George E. Ehrlich
Journal: JAMA (1978)

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
Tissue eicosanoids and vascular permeability in rats with chronic biliary obstruction
Authors: N Ohara
Journal: Hepatology (1993)

Advanced cirrhosis is known to be associated with extrahepatic organ dysfunction, but the mechanism for this cirrhosis complication is largely unknown. We measured tissue albumin leakage in rats with biliary cirrhosis or acute cholestasis and tested the hypothesis that arachidonic acid metabolites contribute to the vascular permeability change. Six weeks after bile duct ligation, rats with biliary cirrhosis exhibited increased extravascular leakage of 125I-albumin in lung (p < 0.001) and kidney (p < 0.01) but not in heart or brain. In contrast, in cholestatic rats 10 days after bile duct ligation, only the kidney albumin leak was significantly increased (p < 0.01). Tissue thromboxane B2 levels, measured with an enzyme immunoassay, were increased in lung, kidney and liver of cirrhotic and cholestatic rats. To determine whether thromboxane A2 contributes to the vascular permeability defects in cirrhosis, we pretreated cirrhotic rats with the thromboxane synthase inhibitor dazoxiben (10 mg/kg intraperitoneally every 8 hr) for 20 hr before assessment of vascular permeability. Dazoxiben blocked the increase in thromboxane B2 level in lung but not in kidney and lowered the lung but not the kidney albumin leak index. In cholestatic rats given a higher dose of dazoxiben (40 mg/kg intraperitoneally every 8 hr) for 20 hr, the kidney thromboxane B2 level but not albumin leak was significantly lowered. We conclude that chronic biliary obstruction in rats leads to increased vascular permeability in selected extrahepatic organs and that thromboxane A2 contributes to the vascular permeability increase in the lung. Whether thromboxane A2 plays a role in renal albumin leakage will require further study. (HEPATOLOGY 1993;18:111–118).
Absence of Thyroid Hormone Activation during Development Underlies a Permanent Defect in Adaptive Thermogenesis
Authors: Jessica A. Hall, Scott Ribich, Marcelo A. Christoffolete, Gordana Simovic, Mayrin Correa-Medina, Mary Elizabeth Patti, Antonio C. Bianco
Journal: Endocrine Reviews (2010)

Abstract Type 2 deiodinase (D2), which is highly expressed in brown adipose tissue (BAT), is an enzyme that amplifies thyroid hormone signaling in individual cells. Mice with inactivation of the D2 pathway (D2KO) exhibit dramatically impaired thermogenesis in BAT, leading to hypothermia during cold exposure and a greater susceptibility to diet-induced obesity. This was interpreted as a result of defective acute activation of BAT D2. Here we report that the adult D2KO BAT has a permanent thermogenic defect that stems from impaired embryonic BAT development. D2KO embryos have normal serum T3 but due to lack of D2-generated T3 in BAT, this tissue exhibits decreased expression of genes defining BAT identity [i.e. UCP1, PGC-1α and Dio2 (nonfunctional)], which results in impaired differentiation and oxidative capacity. Coinciding with a reduction of these T3-responsive genes, there is oxidative stress that in a cell model of brown adipogenesis can be linked to decreased insulin signaling and decreased adipogenesis. This discovery highlights the importance of deiodinase-controlled thyroid hormone signaling in BAT development, where it has important metabolic repercussions for energy homeostasis in adulthood.
The interaction between <scp>L</scp>yn and <scp>F</scp>cε<scp>RI</scp>β is indispensable for <scp>F</scp>cε<scp>RI</scp>‐mediated human mast cell activation
Authors: Y. Okayama, J.‐I. Kashiwakura, A. Matsuda, T. Sasaki‐Sakamoto, S. Nunomura, N. Yokoi, N. Ebihara, K. Kuroda, K. Ohmori, H. Saito, C. Ra
Journal: Allergy (2012)

Abstract Background F cε RI β reportedly functions as an amplifier of the F cε RI γ‐mediated activation signal using a reconstitution system. However, the amplification mechanisms in human mast cells ( MC s) are poorly understood. We previously reported the hyperexpression of F cε RI β of MC s in giant papillae from vernal keratoconjunctivitis patients, compared with that in conjunctivae from nonallergic conjunctivitis patients. Elucidation of the molecular mechanisms of the amplification induced by F cε RI β should provide new targets for novel therapeutic interventions. The aim is to understand in greater details the function of F cε RI β in human MC F cε RI expression and signaling. Methods F cε RI β and L yn expression was reduced using a lentiviral sh RNA silencing technique. Localization of L yn and F cε RI β in cultured MC s was examined by confocal microscopic analysis. Mediators were measured by ELISA s. Results The diminution of F cε RI β significantly downregulated cell surface F cε RI expression and F cε RI ‐mediated mediator release/production. The downregulation of F cε RI ‐mediated degranulation was not only due to the decrease in F cε RI expression. The diminution of F cε RI β inhibited the redistribution of L yn within the cell membrane following I g E sensitization. The diminution of L yn in MC s significantly downregulated F cε RI ‐mediated degranulation. The recombinant cell‐penetrating forms of phosphorylated F cε RI β immunoreceptor tyrosine‐based activation motif ( ITAM ) for intracellular delivery disturbed the interaction between L yn and phosphorylated endogenous F cε RI β ITAM , resulted in inhibiting I g E ‐dependent histamine release from MC s in vitro and from giant papillae specimens ex vivo . Conclusion The interaction between L yn and F cε RI β is indispensable for F cε RI ‐mediated human MC activation, and specific inhibition of the interaction may represent a new therapeutic strategy for the treatment of human allergic diseases.