tbuckley/cabot-search huggingface dataset:
Decreased insulin activation of glycogen synthase in skeletal muscles in young nonobese Caucasian first-degree relatives of patients with non-insulin-dependent diabetes mellitus.
Authors: A Vaag, J E Henriksen, H Beck-Nielsen
Journal: Journal of Clinical Investigation (1992)

Insulin resistance in non-insulin-dependent diabetes is associated with a defective insulin activation of the enzyme glycogen synthase in skeletal muscles. To investigate whether this may be a primary defect, we studied 20 young (25 +/- 1 yr) Caucasian first-degree relatives (children) of patients with non-insulin-dependent diabetes, and 20 matched controls without a family history of diabetes. Relatives and controls had a normal oral glucose tolerance, and were studied by means of the euglycemic hyperinsulinemic clamp technique, which included performance of indirect calorimetry and muscle biopsies. Insulin-stimulated glucose disposal was decreased in the relatives (9.2 +/- 0.6 vs 11.5 +/- 0.5 mg/kg fat-free mass per (FFM) min, P less than 0.02), and was due to a decreased rate of insulin-stimulated nonoxidative glucose metabolism (5.0 +/- 0.5 vs 7.5 +/- 0.4 mg/kg fat-free mass per min, P less than 0.001). The insulin-stimulated, fractional glycogen synthase activity (0.1/10 mmol liter glucose-6-phosphate) was decreased in the relatives (46.9 +/- 2.3 vs 56.4 +/- 3.2%, P less than 0.01), and there was a significant correlation between insulin-stimulated, fractional glycogen synthase activity and nonoxidative glucose metabolism in relatives (r = 0.76, P less than 0.001) and controls (r = 0.63, P less than 0.01). Furthermore, the insulin-stimulated increase in muscle glycogen content over basal values was lower in the relatives (13 +/- 25 vs 46 +/- 9 mmol/kg dry wt, P = 0.05). We conclude that the defect in insulin activation of muscle glycogen synthase may be a primary, possibly genetically determined, defect that contributes to the development of non-insulin-dependent diabetes.
Headache caused by caffeine withdrawal among moderate coffee drinkers switched from ordinary to decaffeinated coffee: a 12 week double blind trial.
Authors: M van Dusseldorp, M B Katan
Journal: BMJ (1990)

Lemeshow. There were no significant differences between the two control groups with any of the risk factors considered. Body mass index was 25-55 (SD 3-59) in patients; 26-20 (3-63) in the general population controls; and 25-47 (5-15) in hospital controls. Comparing patients with each control group we found a significantly increased risk of myocardial infarction among patients who snored every night (table). Multiple logistic regression analysis showed that this association was independent of other risk factors.
Notch alters VEGF responsiveness in human and murine endothelial cells by direct regulation of VEGFR-3 expression
Authors: Carrie J. Shawber, Yasuhiro Funahashi, Esther Francisco, Marina Vorontchikhina, Yukari Kitamura, Stephanie A. Stowell, Valeriya Borisenko, Nikki Feirt, Simona Podgrabinska, Kazuko Shiraishi, Kallayanee Chawengsaksophak, Janet Rossant, Domenico Accili, Mihaela Skobe, Jan Kitajewski
Journal: Journal of Clinical Investigation (2007)

The Notch family of cell surface receptors and its ligands are highly conserved proteins that regulate cell fate determination, including those involved in mammalian vascular development. We report that Notch induces VEGFR-3 expression in vitro in human endothelial cells and in vivo in mice. In vitro, Notch in complex with the DNA-binding protein CBF-1/suppressor of hairless/Lag1 (CSL) bound the VEGFR-3 promoter and transactivated VEGFR-3 specifically in endothelial cells. Through induction of VEGFR-3, Notch increased endothelial cell responsiveness to VEGF-C, promoting endothelial cell survival and morphological changes. In vivo, VEGFR-3 was upregulated in endothelial cells with active Notch signaling. Mice heterozygous for null alleles of both Notch1 and VEGFR-3 had significantly reduced viability and displayed midgestational vascular patterning defects analogous to Notch1 nullizygous embryos. We found that Notch1 and Notch4 were expressed in normal and tumor lymphatic endothelial cells and that Notch1 was activated in lymphatic endothelium of invasive mammary micropapillary carcinomas. These results demonstrate that Notch1 and VEGFR-3 interact genetically, that Notch directly induces VEGFR-3 in blood endothelial cells to regulate vascular development, and that Notch may function in tumor lymphangiogenesis.
Prevalence of Diabetes in Chinese Adults
Authors: Chuanwen Lu, Wenjie Sun
Journal: JAMA (2014)

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
Parkinson's Law in Medicine
Authors: Geza de Takats
Journal: New England Journal of Medicine (1960)

IN a delightful satire,1 which every executive, department head or hospital administrator ought to read, C. Northcote Parkinson, professor of history at the University of Malaya, enunciated an important law. It was during the war, while he was in the British Army, that the workings of "The Law" dawned on him. He was serving at a combined headquarters under four officers. At one point the colonel took sick; his assistant had to go away, the third in command soon left on business, and, finally, the fourth was called away for some reason or other. While this was happening, Parkinson noticed . . .
Smoking Habits of Men Employed in Industry, and Mortality
Authors: G. Z. Brett, B. Benjamin
Journal: BMJ (1968)

A study of the relation between smoking habits and lung cancer in male industrial workers over a period of three years has confirmed the earlier findings in doctors that the death-rate from lung cancer correlates closely with the number of cigarettes smoked. Of 54,460 men studied 68.7% were current cigarette smokers. The annual mortality rate from lung cancer was 0.33 per thousand in non-smokers and ex-smokers, and 1.2 per thousand for all cigarette smokers, and higher in heavy smokers. Heavy cigarette smokers who retained the cigarette in the mouth between puffs (“drooping” cigarette habit) had an annual mortality rate of 4.1 per thousand. The mortality from coronary thrombosis in smokers was nearly three times that in non-smokers. A mortality gradient with rising consumption of cigarettes was observed. Some correlation between smoking and cancer of other sites and from non-neoplastic lung disease was observed in older men, but no correlation was found with other cardiovascular diseases and cerebrovascular diseases.
Intense Myocardial Uptake of Gallium-67 Citrate and Technetium-99m Pyrophosphate in a Uremic Patient
Authors: TAPAN K. CHAUDHURI
Journal: Clinical Nuclear Medicine (1985)

A uremic patient showed marked myocardial uptake of Ga-67 citrate and Tc-99m pyrophosphate. The pattern and distribution of the uptake suggested that the concentration of the activity was mainly in the myocardium. The mechanism of intense myocardium tracer uptake may be attributed to one or both of the diffuse pathological processes (uremic myocarditis and/or uremic microcalcification) that occur in uremia.
Diplopia Following Ibuprofen Administration
Authors: Jack Asherov
Journal: JAMA (1982)

To the Editor.—  Ocular symptoms related to ibuprofen (Motrin) administration are rare and include reduced visual acuity, 1 toxic amblyopia, 2 severe pain behind the eyes, visual hallucinations, visual field defect, uveitis, conjunctivitis, and keratosis. 3 Recently, we observed a patient who experienced diplopia following ibuprofen administration.  Report of a Case.—  A 52-year-old woman with seronegative rheumatoid arthritis began treatment with ibuprofen, 400 mg four times daily. No other medications were taken by the patient. Three days later, diplopia appeared. Ibuprofen therapy was discontinued and aspirin therapy was started. An eye examination was performed and all test results were within normal limits. Her complaints disappeared two days after she discontinued taking ibuprofen. In the last year, while receiving buffered aspirin, she has had no visual disturbances.
Regional wall motion from radiopaque markers after intravenous and intracoronary injections of nifedipine.
Authors: P W Serruys, R W Brower, H J ten Katen, A H Bom, P G Hugenholtz
Journal: Circulation (1981)

SlUMMARY In 11 patients, 1 mg of i.v.nifedipine was administered over 3 minutes and regional wall motion was studied during atrial pacing.The dominant effect of nifedipine at basal heart rate (HR) was a lowering of peak left ventricular pressure (152 to 128 mm Hg) with an increase in HR from 70 to 86 beats/min.During pacing, nifedipine produced (p < 0.02) a similar reduction in pressure at all rates, which is a mechanism reduc- ing or sparing myocardial oxygen consumption.At the highest paced rate, the maximal velocity (Vmax) of the contractile element was significantly (p < 0.02) increased from 61 to 68 sec-' and the regional shortening frac- tions were increased over the entire pacing range: basal HR, 13.7% to 14.6% (p < 0.025); HR 120 beats/min, 11.6% to 13.5% (p < 0.005); maximal HR, 10.9% to 11.8% (p < 0.05).No evidence of a negative inotropic effect after i.v.administration of nifedipine was observed, myocardial oxygen consumption was probably reduced and there was an increase in regional function.Nifedipine (0.1 mg within 10 seconds) was selectively injected into bypass grafts at a constant paced rate in 10 patients.Seventeen marker pair regions were directly supplied by bypasses selectively injected with nifedipine (group A), and nine were independently perfused (group B).The pressure-derived variables showed a direct negative inotropic effect and a slowed relaxation phase.Thirty seconds after injection, minimal marker separation in group A occurred 78 msec after end-systole (ES), whereas before injection, minimal marker separation occurred 39 msec before ES (p < 0.0001).At the same time, the relation between minimal marker separation and ES in group B was unaffected.In consequence, the regional shortening fraction in group A con- tributing to left ventricular ejection decreased significantly 30 seconds after injection (-32%, p < 0.01), while that calculated simply from minimal and maximal marker separation remained unchanged (-9%, NS).Active regional contraction starting after the beginning of ejection and ending after ES must be considered as asynchrony and can be considered responsible for the slowed isovolumic contraction and relaxation of the whole ventricle.The dominant effect of i.v.nifedipine at clinical dosage levels is a lowering of systemic blood pressure, possibly reducing oxygen demand.When regionally administered, nifedipine exerts a direct negative inotropic effect, but after i.v.injection, this effect is overridden by reflex increases in contractility and in heart rate as a result of lowered systemic arterial pressure.
Pattern Of Cd28 Expression On Cd8+ T Cells In A Group Of Coinfected And Monoinfected HIV And HCV Patients
Authors: A. Paravisini, M.S. Cianchetta, R. Garcia, S. Raso, P. Llorente, M. Fernandez-Guerrero, M. Gorgolas
Journal: Journal of Allergy and Clinical Immunology (2007)
Localization of Tc-99m MDP in the Rectus Abdominis Muscle Without Associated Symptoms
Authors: Leonard P. Connolly, Laura A. Drubach, S. Ted Treves
Journal: Clinical Nuclear Medicine (2003)

Skeletal tracer localization in the rectus abdominis muscle of a 17-year-old girl whose training regimen included vigorous abdominal exercise but who had no abdominal soreness is described. The case illustrates that bone tracers may localize to skeletal muscle without associated symptoms. This is consistent with bone tracer localization in skeletal muscle reflecting subtle fiber abnormalities rather than necrosis.
Osteoclast-Derived Matrix Metalloproteinase-7, but Not Matrix Metalloproteinase-9, Contributes to Tumor-Induced Osteolysis
Authors: Sophie Thiolloy, Jennifer Halpern, Ginger E. Holt, Herbert S. Schwartz, Gregory R. Mundy, Lynn M. Matrisian, Conor C. Lynch
Journal: Cancer Research (2009)

Abstract The matrix metalloproteinases MMP-2, MMP-3, MMP-7, MMP-9, and MMP-13 are highly expressed in the tumor-bone microenvironment, and, of these, MMP-7 and MMP-9 were found to be localized to bone-resorbing osteoclasts in human breast-to-bone metastases. In a bid to define the roles of host-derived MMP-7 and MMP-9 in the tumor-bone microenvironment, the tibias of MMP-7 and MMP-9 null mice were injected with osteolytic luciferase–tagged mammary tumor cell lines. Our data show that osteoclast-derived MMP-7 significantly contributes to tumor growth and tumor-induced osteolysis whereas osteoclast-derived MMP-9 had no effect on these processes. MMP-7 is capable of processing a number of nonmatrix molecules to soluble active forms that have profound effects on cell-cell communication, such as RANKL, a crucial mediator of osteoclast precursor recruitment and maturation. Therefore, the ability of osteoclast-derived MMP-7 to promote RANKL solubilization in the tumor-bone microenvironment was explored. Results revealed that levels of soluble RANKL were significantly lower in the MMP-7 null mice compared with wild-type (WT) controls. In keeping with this observation, MMP-7 null mice had significantly fewer osteoclast numbers at the tumor-bone interface compared with the WT controls. In summary, we propose that the solubilization of RANKL by MMP-7 is a potential mechanism through which MMP-7 mediates mammary tumor–induced osteolysis. Our studies indicate that the selective inhibition of MMP-7 in the tumor-bone microenvironment may be of benefit for the treatment of lytic breast-to-bone metastases. [Cancer Res 2009;69(16):6747–55]
Developing a register of randomised controlled trials in primary care.
Authors: C Silagy
Journal: BMJ (1993)

OBJECTIVE--To determine the number, nature, site of publication, and feasibility of identifying randomised controlled trials relevant to primary care. DESIGN--Review of literature using three strategies: approaching journal editors, Medline search, and manual search of individual journals. SETTING--Journals containing publications of studies based in primary care. MAIN OUTCOME MEASURES--The number, site of publication, and subject of trials identified. RESULTS--No journal had a system which enabled identification of all the randomised controlled trials it published. 266 trials relevant to primary care were identified from 110 different journals during 1987-91 by Medline. Of these, only 62 trials were published in primary care journals. Hand searching of seven major primary care research journals showed that between 13% and 38% of the trials had been missed by the Medline search. Of the trials identified, 47 (18%) were concerned with mental disease (including neuroses, tobacco misuse and alcohol misuse) and 43 (16%) were concerned with hypertension. CONCLUSION--Given the diversity of publication sources and topics, this supports the need for a centrally based register of randomised controlled trials that may be relevant to primary care overviews in the future.
Tumour necrosis factor is an important mediator of portal and systemic haemodynamic derangements in alcoholic hepatitis
Authors: R P Mookerjee, S Sen, N A Davies, S J Hodges, R Williams, R Jalan
Journal: Gut (2003)

The role of proinflammatory cytokines in the pathogenesis of portal hypertension is unclear.This study tests the hypothesis that tumour necrosis factor alpha (TNF-alpha) is an important mediator of the circulatory disturbances in alcoholic hepatitis (AH) and evaluates the acute and short term effect of a single infusion of the monoclonal chimeric anti-TNF-alpha antibody (Infliximab) on portal and systemic haemodynamics in 10 patients with severe biopsy proven AH. Cardiovascular haemodynamics, hepatic venous pressure gradient (HVPG), and hepatic and renal blood flow were measured before, 24 hours after Infliximab, and prior to hospital discharge.Serum bilirubin (p<0.05), C reactive protein (p<0.001), and white cell count (p<0.01) were reduced significantly, as were plasma levels of interleukin (IL)-6 and IL-8 after treatment. Of the 10 patients, nine were alive at 28 days. Mean HVPG decreased significantly at 24 hours (23.4 (2.8) to 14.3 (1.9) mm Hg; p<0.001) with a sustained reduction prior to discharge (12.8 (1.9) mm Hg; p<0.001). Mean arterial pressure and systemic vascular resistance increased significantly (p<0.001and p<0.01, respectively), mirrored by a reduction in cardiac index (5.9 (0.5) to 4.7 (0.5) l/min/m(2); p<0.05) prior to discharge. Hepatic and renal blood flow also increased significantly (506.2 (42.9) to 646.3 (49.2) ml/min (p=0.001) and 424.3 (65.12) to 506.3 (85.7) ml/min (p=0.001), respectively) prior to discharge.The results of this study illustrate that anti-TNF-alpha treatment in AH patients produces a highly significant, early, and sustained reduction in HVPG, possibly through a combination of a reduction in cardiac output and intrahepatic resistance. In addition, there was a reduction in hepatic inflammation and improved organ blood flow, suggesting an important role for TNF-alpha in mediating the circulatory disturbances in AH.
Discordance between Expression and Genome Transfer Titering of HSV Amplicon Vectors: Recommendation for Standardized Enumeration
Authors: W.J. Bowers, D.F. Howard, H.J. Federoff
Journal: Molecular Therapy (2000)

Herpes simplex virus-derived amplicon vectors are well suited to the development of gene-based therapy for neurodegenerative diseases. The plasmid-based amplicon vector system allows for facile introduction of transcription units, possesses the potential for carrying gene inserts up to approximately 130 kb in length, and can be packaged into infectious virus devoid of contaminating cytotoxic helper virus. For accurate assessments to be made regarding vector comparison and improvements in vector design, a standard for titering prepared virus stocks must be established. At present, packaged amplicon vectors are routinely titered using reporter gene expression units to quantitate numbers of infectious amplicon virions. The strength of the promoter, sensitivity of detection of the gene product, and choice of titering cell type can greatly influence the apparent numbers of infectious virus particles. This is especially evident when comparisons are made between two amplicon vectors that possess different promoters. To this end, we have developed a new titering method based on a real-time quantitative PCR technique that allows for enumeration of transducing particles. This new approach ensures that amplicon comparison experiments are initiated with equivalent transduction units, thus allowing for a fair assessment of expression and therapeutic efficacy differences.
Intestinal lymphoma complicating dermatitis herpetiformis
Authors: D.B.A. SILK, N.A.G. MOWAT, R.H. RIDDELL, J.D. KIRBY
Journal: British Journal of Dermatology (1977)

A case is reported of a patient with dermatitis herpetiformis who has developed an intestinal lymphoma and a bladder carcinoma during the course of his illness. When considered in conjunction with three recently reported cases it is suggested that intestinal lymphoma may complicate the enteropathy of dermatitis herpetiformis.
Programme to encourage self-examination for breast cancer.
Authors: G Gastrin
Journal: BMJ (1980)

Carboxyhaemoglobin concentrations were used to assess compliance.Only patients in whom the concentrations fell to under 2% during the no-smoking period were included in the study.Concentrations of up to 2% during no-smoking periods are acceptable: non-smokers living and working in the City of London have a mean concentration of 1-3%.12During the smoking periods our patients had carboxyhaemoglobin concentrations in excess of 4%.This study has shown that smoking in addition to its known epidemiological associations has direct and adverse effects on the heart.These were still evident after treatment with propranolol and represent a hindrance to the effective medical treatment of angina pectoris.
Autoimmune thrombocytopenia in Waldenstr�m's macroglobulinemia
Authors: R.G. Owen, A. Lubenko, J. Savage, L.A. Parapia, A.S. Jack, G.J. Morgan
Journal: American Journal of Hematology (2001)

Autoimmune phenomena are well-recognised complications of Waldenström's macroglobulinemia (WM) and IgM monoclonal gammopathy. Peripheral neuropathy and cold agglutinin hemolytic anemia are the most common reported and occur in 5-10% of patients. Autoimmune thrombocytopenia has been rarely reported in WM and its incidence is not known. In this study we report the case of a 67-year-old man who presented with autoimmune thrombocytopenia who was subsequently found to have WM. Laboratory investigation demonstrated that platelet-associated IgM (PAIgM) but not PAIgG was clearly elevated compared to normal controls. In addition the patient's serum reacted strongly with a panel of donor platelets analysed with an indirect platelet immunofluorescence assay utilising an anti-IgM secondary antibody. Glycoprotein specificity could not however be demonstrated by ELISA techniques for platelet glycoproteins IIbIIIa, IaIIa, IbIXa, and IV. We also reviewed the case records of 104 additional cases of WM diagnosed at our institution between 5/93 and 5/99. Three further cases with clinically significant autoimmune thrombocytopenia were identified. The overall incidence of autoimmune thrombocytopenia (4/105, 3.8%) in this cohort of patients was similar to the incidence of peripheral neuropathy (7/105, 6.7%) and cold agglutinins (3/105, 2.9%).
Topical Use of Hydroquinone for Depigmentation
Authors: Malcolm C. Spencer
Journal: JAMA (1965)

Autoxidation of hydroquinone in ointments used for depigmentation may reduce its effectiveness. In this study low concentrations (2%, 3%, 5%) of stabilized hydroquinone were used for depigmenting "old age spots" on the hands of 94 white men. Also treated were 43 Negro men with normal skin. Higher concentrations of hydroquinone may produce sensitization. Lower concentrations are less likely to. Although the depigmentation produced by topical hydroquinone is limited, it is, in our experience, the best available depigmenting agent.
Relief of Profound Feedback Inhibition of Mitogenic Signaling by RAF Inhibitors Attenuates Their Activity in BRAFV600E Melanomas
Authors: Piro Lito, Christine A. Pratilas, Eric W. Joseph, Madhavi Tadi, Ensar Halilovic, Matthew Zubrowski, Alan Huang, Wai Lin Wong, Margaret K. Callahan, Taha Merghoub, Jedd D. Wolchok, Elisa de Stanchina, Sarat Chandarlapaty, Poulikos I. Poulikakos, James A. Fagin, Neal Rosen
Journal: Cancer Cell (2012)