tbuckley/cabot-search huggingface dataset:
A unique control mechanism in the regulation of insulin secretion. Secretagogue-induced somatostatin receptor recruitment.
Authors: B Draznin, J W Leitner, K E Sussman
Journal: Journal of Clinical Investigation (1985)

In this study, we have correlated the translocation of somatostatin (SRIF) receptors from the cell interior to the plasma membrane with the ability of SRIF to inhibit insulin release. Islets were perifused with glucose (30, 100, 165, 200, or 300 mg/dl) in the presence of sodium isethionate. Sodium isethionate inhibits insulin release, but not the recruitment of SRIF receptors. Thus, the recruitment of SRIF receptors to the surface membrane continued without the lysis of secretion vesicles. SRIF binding rose from 3.75 +/- 0.16 to 6.46 +/- 0.28 fmol/10 islets as glucose concentration increased. Sodium isethionate was then removed, islets perifused with low glucose (30 mg/dl), and challenged with 400 microM isobutylmethylxanthine (IBMX) with or without SRIF (5 micrograms/ml). In the islets perifused with high glucose concentration, IBMX lysed a greater number of vesicles and caused enhanced release of insulin. The greater the number of secretion vesicles marginated to the plasma membrane by glucose, the greater the response to IBMX. Colchicine (1 mM) prevented secretion vesicle migration and this potentiation effect of higher concentrations of glucose was eliminated. In experiments with IBMX and SRIF, the degree of inhibition of IBMX-induced insulin release by SRIF was proportional to the magnitude of SRIF binding to these islets. SRIF inhibited insulin release by 20 microU/100 islets initially perifused with low glucose (30 mg/dl) and by 875 microU/100 islets perifused with high glucose (300 mg/dl). The maximal effect of SRIF was observed when its binding reached a level of 5.4 fmol/10 islets. We conclude that inhibition of insulin release by SRIF is proportional to the SRIF receptor concentration, and that translocation of SRIF receptors during exocytosis plays an important role in paracrine regulation of insulin secretion by rendering the islets more sensitive to SRIF.
Mechanisms of Angina Pectoris or Heart Pain.
Authors: Joseph T. Roberts
Journal: Annals of Internal Medicine (1964)

s1 February 1964Mechanisms of Angina Pectoris or Heart Pain.Joseph T. Roberts, M.D., F.A.C.P.Joseph T. Roberts, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-2-318_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptCardiac referred pain is best explained on the basis of a reflex vasoneuropathy due to ischemia of peripheral somatic nerves in the area of referred pain of cardiac origin. This neural ischemia is due to spasm of the vasa nervorum or small blood vessels in the peripheral nerves affecting the various types of axones in such nerves and thereby increasing or blocking their usual functions according to the degree of ischemia. A reflex has been demonstrated in dogs and rabbits whereby the vasa nervorum of the left arm especially constrict sharply after acute coronary artery ligation in a reversible and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Buffalo, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1964Volume 60, Issue 2_Part_1Page: 318-319KeywordsAnginaBlood vesselsCoronary arteriesHeartIschemiaLigation assayNervesRabbitsReflexes Issue Published: 1 February 1964 PDF DownloadLoading ...
Single cell analysis shows decreasing FoxP3 and TGFβ1 coexpressing CD4+CD25+ regulatory T cells during autoimmune diabetes
Authors: Shannon M. Pop, Carmen P. Wong, Donna A. Culton, Stephen H. Clarke, Roland Tisch
Journal: The Journal of Experimental Medicine (2005)

Natural CD4+CD25+ regulatory T (CD4+CD25+ T reg) cells play a key role in the immunoregulation of autoimmunity. However, little is known about the interactions between CD4+CD25+ T reg cells and autoreactive T cells. This is due, in part, to the difficulty of using cell surface markers to identify CD4+CD25+ T reg cells accurately. Using a novel real-time PCR assay, mRNA copy number of FoxP3, TGFβ1, and interleukin (IL)-10 was measured in single cells to characterize and quantify CD4+CD25+ T reg cells in the nonobese diabetic (NOD) mouse, a murine model for type 1 diabetes (T1D). The suppressor function of CD4+CD25+CD62Lhi T cells, mediated by TGFβ, declined in an age-dependent manner. This loss of function coincided with a temporal decrease in the percentage of FoxP3 and TGFβ1 coexpressing T cells within pancreatic lymph node and islet infiltrating CD4+CD25+CD62Lhi T cells, and was detected in female NOD mice but not in NOD male mice, or NOR or C57BL/6 female mice. These results demonstrate that the majority of FoxP3-positive CD4+CD25+ T reg cells in NOD mice express TGFβ1 but not IL-10, and that a defect in the maintenance and/or expansion of this pool of immunoregulatory effectors is associated with the progression of T1D.
US doctors want to be paid for email communication with patients
Authors: Scott Gottlieb
Journal: BMJ (2004)

Email is becoming a more common tool of clinical practice, enabling doctors to communicate with patients between office visits, improve diagnosis and compliance with medical treatments, and facilitate medical record keeping, says a report in the New England Journal of Medicine (2004;350: 1705-7).

“Judging from our early experience in a practice that offers secure electronic communication, e-mail gives doctors and patients more …
Centres for treatment of drug addiction. Importance of research.
Authors: P. H. Connell
Journal: BMJ (1967)

Centres for Treatment of Drug AddictionBIwNT '=L 499 At present the projected legislation will restrict the prescribing of only heroin and cocaine.As cocaine is not a drug that can produce physical dependence there is no reason to prescribe this drug in any circumstances.There may have to be an extension of the drugs restricted at a later date, as already many addicts who have taken heroin and cocaine in the past take intravenous methadone combined with methedrine at present.Prescribing methadone for addicts is not desirable.If there is to be medical control it is better dispensed and given orally under supervision.Whether patients of this type can best be treated voluntarily or compulsorily will have to be considered.The most convincing follow-up studies up to the present have shown that a period of compulsory treatment followed by a probationary period on licence produced better results than purely voluntary or purely custodial methods of treatment.4
Membrane potential of rat ventricular myocytes responds to axial stretch in phase, amplitude and speed‐dependent manners
Authors: S NISHIMURA, Y KAWAI, T NAKAJIMA, Y HOSOYA, H FUJITA, M KATOH, H YAMASHITA, R NAGAI, S SUGIURA
Journal: Cardiovascular Research (2006)

Objective: To elucidate the interdependence between the mechanical state of the myocardium and its electrical activity, previous studies have been performed at the cellular level. However, the information to date has been limited by the technical difficulties associated with stretching single myocytes.
On Revision of the Code.
Authors: E. Cutter
Journal: JAMA (1894)

New York, April 24, 1894. <h3>To the Editor:</h3> —The venerable father of theAssociationin the issue of April 4,1894, in his disapproval of the revision of the Code of Ethics asks the question: "In what direction this progress?—that of science and honor, or that of mammon and dishonor?" Now, as he has asked, it is discourteous not to reply. Also, this is the time for members to speak out their sentiments, as a matter of history and material for action. Dr. Davis says the Committee has<i>emasculated</i>the section on patents and proprietary medicines, making it prohibit only patents "for secret nostrums" (<i>i</i>.<i>e</i>., ours, from<i>nos</i>—we); "a medicine the ingredients of which are kept secret to restrict profits to proprietor or inventor."—Webster; in other words, for " mammon and dishonor." I have no doubt that the majority of the members have used antipyrin, phenacetin and sulfonal, out of
Causes of pulmonary impairment in asbestos-exposed individuals with diffuse pleural thickening.
Authors: S T Kee, G Gamsu, P Blanc
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

To examine whether diffuse pleural thickening (DPT) causes impairment of pulmonary function independent of other manifestations of asbestos-related disease, we studied individuals selected from 1,150 men with occupational asbestos exposure who had undergone pulmonary function testing and computed tomographic (CT) scanning. The CT scans revealed 84 subjects with DPT as defined for CT. Of these 84 subjects, 53 eligible study cases were matched by age with a referent group without DPT from the same exposed group. No difference was demonstrated between cases and referents in smoking history, length of exposure, latency, or the proportion with either interstitial fibrosis or pleural plaques. Individuals with DPT demonstrated significantly reduced forced vital capacity (FVC) (p = 0.002) and diffusing capacity for carbon monoxide (DLCO) (p = 0.002) as compared with the referents. No difference was found in the two groups' FEV1 to FVC ratio (FEV1/FVC). Individuals with DPT and either interstitial fibrosis or pleural plaques showed a significantly lower FVC than did those with fibrosis or pleural plaques alone. Individuals with DPT and rounded atelectasis had similar pulmonary function to those with DPT and no rounded atelectasis. Subjects with DPT had a more frequent history of coronary bypass surgery than referents (19% versus 2%; p = 0.008). We conclude that subjects with DPT have restrictive pulmonary function and reduced diffusing capacity independent of other manifestations of asbestos-related disease.
Recombinant human tumor necrosis factor alpha suppresses autoimmune diabetes in nonobese diabetic mice.
Authors: J Satoh, H Seino, T Abo, S Tanaka, S Shintani, S Ohta, K Tamura, T Sawai, T Nobunaga, T Oteki
Journal: Journal of Clinical Investigation (1989)

We previously reported that administration of a streptococcal preparation (OK-432) inhibited insulitis and development of autoimmune diabetes in nonobese diabetic (NOD) mice and BB rats as animals models of insulin-dependent diabetes mellitus. In this study, we screened various cytokines that could be induced by OK-432 in vivo, for their preventive effect against diabetes in NOD mice. Among recombinant mouse IFN gamma, human IL1 alpha, human IL2, mouse granulocyte-macrophage colony-stimulating factor and human TNF alpha, only human TNF alpha suppressed insulitis and significantly (P less than 0.001) inhibited development of diabetes. NOD mice were the lowest producers of the mRNA of TNF and serum TNF on stimulation with OK-432 or with IFN gamma plus LPS, compared with C57BL/6, C3H/He, and Balb/c mice. The results imply a role for low productivity of TNF in the pathogenesis of autoimmune diabetes in NOD mice.
Inhibition of the mitochondrial oxidation of fatty acids by tetracycline in mice and in man: Possible role in microvesicular steatosis induced by this antibiotic
Authors: Eric Fréneaux, Gilles Labbe, Philippe Letteron, The Le Dinh, Claude Degott, Jean Genève, Dominique Larrey, Dominique Pessayre
Journal: Hepatology (1988)

Intravenous administration of high doses of tetracycline may produce severe microvesicular steatosis of the liver in man. A similar disease is observed after ingestion of drugs which inhibit hepatic mitochondrial fatty acid beta-oxidation and in subjects with various inborn defects in this metabolic pathway. We therefore determined the effects of tetracycline on the mitochondrial oxidation of fatty acids in mice and in man. In vitro, addition of tetracycline 0.25, 0.5, 1 or 2 mM inhibited by 15, 38, 56 and 65%, respectively, the formation of beta-oxidation products during incubation of palmitic acid with mouse liver mitochondria and the various cofactors necessary for beta-oxidation. Inhibition was reversible. Inhibition appeared even greater with human liver mitochondria. Tricarboxylic acid cycle activity, assessed by the in vitro formation of [14C]CO2 from [1-14C]acetylcoenzyme A by mouse liver mitochondria, was inhibited by 25, 32 and 43%, respectively, in the presence of 0.5, 1 or 2 mM of tetracycline. In vivo, administration of tetracycline, 0.25 or 1 mmole per kg, inhibited by 53 and 84%, respectively, the exhalation of [14C]CO2 during the first 3 hours following the administration of a tracer dose of [U-14C]palmitic acid. Administration of tetracycline, 0.0625, 0.25 or 1 mmole per kg, 6 hr before the measurement, increased hepatic triglycerides by 100, 170 and 250%, respectively. After 1 mmole per kg, accumulation of hepatic triglycerides was maximum at 24 hr, reaching 9-fold the control value; liver histology showed microvesicular steatosis at 6 and 24 hr. We conclude that tetracycline inhibits the mitochondrial oxidation of fatty acids in mice and in man.(ABSTRACT TRUNCATED AT 250 WORDS)
Fractalkine Over Expression Suppresses α-Synuclein-mediated Neurodegeneration
Authors: Kevin R Nash, Peter Moran, Dylan J Finneran, Charles Hudson, Jesse Robinson, Dave Morgan, Paula C Bickford
Journal: Molecular Therapy (2014)

In Parkinson's disease, α-synuclein is known to activate microglia and this activation has been proposed as one of the mechanisms of neurodegeneration. There are several signals produced by neurons that have an anti-inflammatory action on microglia, including CX3CL1 (fractalkine). We have shown that a soluble form of CX3CL1 is required to reduce neuron loss in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice and that fractalkine agonism can reduce neuron loss in a 6-hydroxydopamine lesion model. Here, we show that fractalkine can reduce α-synuclein-mediated neurodegeneration in rats. Rats that received fractalkine showed abrogated loss of tyrosine hydroxylase and Neu-N staining. This was replicated in animals where we expressed fractalkine from astrocytes with the glial fibrillary acid protein (GFAP) promoter. Interestingly, we did not observe a reduction in MHCII expression suggesting that soluble fractalkine is likely altering the microglial state to a more neuroprotective one rather than reducing antigen presentation. In Parkinson's disease, α-synuclein is known to activate microglia and this activation has been proposed as one of the mechanisms of neurodegeneration. There are several signals produced by neurons that have an anti-inflammatory action on microglia, including CX3CL1 (fractalkine). We have shown that a soluble form of CX3CL1 is required to reduce neuron loss in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice and that fractalkine agonism can reduce neuron loss in a 6-hydroxydopamine lesion model. Here, we show that fractalkine can reduce α-synuclein-mediated neurodegeneration in rats. Rats that received fractalkine showed abrogated loss of tyrosine hydroxylase and Neu-N staining. This was replicated in animals where we expressed fractalkine from astrocytes with the glial fibrillary acid protein (GFAP) promoter. Interestingly, we did not observe a reduction in MHCII expression suggesting that soluble fractalkine is likely altering the microglial state to a more neuroprotective one rather than reducing antigen presentation.
Cap Polyposis of the Colon and Rectum: An Analysis of Endoscopic Findings
Authors: M. Esaki, T. Matsumoto, H. Kobayashi, T. Yao, S. Nakamura, M. Mizuno, M. Iida, M. Fujishima
Journal: Endoscopy (2001)

Because of the rarity of cap polyposis of the colon and rectum, the endoscopic features of this condition have not been specified to date. The aim of this study is to characterize the endoscopic features of cap polyposis.The diagnosis of cap polyposis was established by histologic findings in specimens obtained endoscopically or surgically from four patients. Colonoscopic findings in the four patients were retrospectively reviewed.The endoscopic features were divided into semipedunculated type (three patients) and flat-topped protruding type (one patient). In the semipedunculated type, the polyps were characterized by reddish protrusions of various configurations with eroded surface in the rectosigmoid colon. In the remaining patient, all the lesions were flat protrusions with a reddish central depression. The polyps of both types became smaller in size and fewer in number at the proximal part of the sigmoid colon. Multiple white specks were observed in the intervening mucosa in all four patients.The prominence of the polyps at the distal part of the colon and rectum and multiple white specks in the intervening mucosa seem to be the additional endoscopic features suggestive of cap polyposis.
Simplified scoring system for newborn.
Authors: W. F. Morrow, T. J. Myles
Journal: BMJ (1969)

A-ActivityNo active movements Some movement but sleepy Good active movements and sluggish B-BreathingNo spontaneous breathing Unsatisfactory breathing-for Unrestricted rhythmical example, gasping, jerky, sustained breathing irregular C-Circulation No heart action Heart rate below 100.Heart rate above 100.Facial cyanosis or pallor No facial cyanosis
Immunologic characterization of the recombinant fire ant venom allergen Sol i 3
Authors: M. Schmidt, T. J. McConnell, D. R. Hoffman
Journal: Allergy (2003)

Individuals sensitized to fire ant stings show immunoglobulin (Ig)E antibodies against the venom protein Sol i 3. We determined the full-length complementary DNA (cDNA) sequence of this protein and expressed recombinant Sol i 3 in immunogenic form. The complete cDNA of Sol i 3 was obtained by reverse transcription polymerase chain reaction (RT-PCR) and PCR + 1 reactions using gene-specific oligonucleotides, and oligonucleotides designed from the amino acid sequence of this protein. The encoding cDNA is 705 bp in length corresponding to 235 amino acids. The first 22 amino acids are a leader sequence. The protein with an added C-terminal hexahistidine tag was expressed in insect cells using a baculovirus system. The recombinant protein was secreted into the supernatant and affinity purified with a cobalt chelating resin. The recombinant fire ant venom allergen Sol i 3 showed similar IgE binding activity to the native protein in radioallergosorbent test (RAST) and RAST inhibition assays. It was produced in both a glycosylated and an unglycosylated form. A three-dimensional reconstruction of Sol i 3 was compared with the experimentally determined structure of the related allergen Ves v 5. This model is supported by results of circular dichroism spectroscopy.
A syndrome of ichthyosis, hepatosplenomegaly and cerebellar degeneration
Authors: P.J. Dykes, R. Marks, P.S. Harper
Journal: British Journal of Dermatology (1979)

Two brothers are described with ichthyosis, hepatosplenomegaly and signs of cerebellar degeneration. The ichthyosis was similar to autosomal dominant ichthyosis both clinically and biochemically. No metabolic abnormality has yet been identified to account for this previously undescribed triad of abnormalities.
Careers of doctors qualifying in Britain in 1974
Authors: J A Gilmore
Journal: BMJ (1982)

Neither of the patients had used other drugs, changed their diet, had any serious illness, or taken more of either medicine than the recommended dose.Both patients were being assessed regularly in an experienced thrombosis service centre.Flurbiprofen is a known in-vitro inhibitor of platelet release and to a lesser degree platelet aggregation.2It has been successfully used in a patient with spontaneous platelet aggregation.4Unfortunately, the bleeding time was not assessed in these patients.A prolonged bleeding time, however, does not account for a prolongation of the prothrombin time as observed in these patients.The only documented investigation of an interaction between flurbiprofen and a coumarin (phenprocoumon) showed slightly enhanced anticoagulation.The authors con- sidered the interaction of little clinical importance.5We recommend that if these drugs are used concurrently, the Thrombotest time should be monitored regularly.Additional prospective interaction studies are required.
A new noninvasive index to predict sustained ventricular tachycardia and sudden death in the first year after myocardial infarction: Based on signal-averaged electrocardiogram, radionuclide ejection fraction and holter monitoring
Authors: J. Anthony Gomes, Stephen L. Winters, Debra Stewart, Steven Horowitz, Mark Milner, Philip Barreca
Journal: Journal of the American College of Cardiology (1987)
Measurement of Radiation Dosage
Authors: Stanley J. Malsky, Bernard Roswit, Charles G. Amato, Harold M. Jones, Blanche Ried, Herman Patterson
Journal: JAMA (1964)

THE IN VIVO MEASUREMENT of x and gamma radiation within human and biological systems is severely limited by the size and accuracy of the detecting system. In vivo dosimeters must be easily implanted and removed and be capable of reinsertion into the same body areas. There are, at the present time, several types of miniature solid state dosimeters that have indicated promise of use as in vivo dosimeters. The two systems considered are radiophotoluminescence ( RPL ) and thermoluminescence (TL). Each of the systems will be discussed separately. <h3>Radiophotoluminescent Glass</h3> The glass acts as a matrix or host which contains a homogeneously distributed fluorescent activator, silver metaphosphate. Upon exposure to x or gamma radiation, the silver metaphosphate is dissociated and some of the ionic silver is reduced to metallic silver of valence zero. Ionizing radiation has, once these reactions are completed, excited the glass so that upon proper stimulation, visible light will
Principles Governing the Genesis of Congenital Malformations Induced in Mice by Hypoxia
Authors: Theodore H. Ingalls, Francis J. Curley
Journal: New England Journal of Medicine (1957)

DURING the past ten years we have been conducting a systematic study of hypoxia as a cause of intra-uterine deaths and congenital defects in mice for the purpose of determining biologic laws underlying the genesis of congenital malformations in mammals.1 A progress report on work done since 19522 and a formulation of basic principles, particularly those determining the development of skeletal anomalies in newborn mice brought about by maternal hypoxia during pregnancy, is given here. The first basic principle to emerge clearly confirmed from work done since 1935 on mammals3 is that a specific kind of defect may be caused . . .
Characterisation of non-histone nuclear proteins cross reactive with purified rheumatoid factors.
Authors: J C Mason, P J Venables, P R Smith, R N Maini
Journal: Annals of the Rheumatic Diseases (1985)

In order to examine the interactions between isolated rheumatoid factors (RFs) and cell nuclear antigens we have prepared 10 RFs by affinity chromatography against IgG coupled to Sepharose. Of these, seven cross reacted with cell nuclei on indirect immunofluorescence. The nuclear antigen appeared to be DNA histones by indirect immunofluorescence on rat liver, though on immunoblotting the rheumatoid factors also reacted with three non-histone polypeptides which were identified in the soluble fraction of nuclear extracts. We were unable to show any relationship between these polypeptides and rheumatoid arthritis nuclear antigen. These reactions represent a hitherto unrecognised phenomenon, which extends the range of antigens recognised by rheumatoid factors. We suggest that the immunopathogenic significance of RFs may not be restricted to their reactivity with IgG, and that non-histone nuclear proteins merit further investigation.