tbuckley/cabot-search huggingface dataset:
Spontaneously increased production of nitric oxide and aberrant expression of the inducible nitric oxide synthase in vivo in the transforming growth factor beta 1 null mouse.
Authors: Y Vodovotz, A G Geiser, L Chesler, J J Letterio, A Campbell, M S Lucia, M B Sporn, A B Roberts
Journal: The Journal of Experimental Medicine (1996)

Transforming growth factor beta 1 null mice (TGF-beta 1-/-) suffer from multifocal inflammation and die by 3-4 wk of age. In these mice, levels of nitric oxide (NO) reaction products in serum are elevated approximately fourfold over levels in controls, peaking at 15-17 d of life. Shortterm treatment of TGF-beta 1-/- mice with NG-monomethyl-L-arginine suppressed this elevated production of NO. Expression of inducible NO synthase (iNOS) mRNA and protein is increased in the kidney and heart of TGF-beta 1-/- mice. These findings demonstrate that TGF-beta 1 negatively regulates iNOS expression in vivo, as had been inferred from mechanistic studies on the control of iNOS expression by TGF-beta 1 in vitro.
Heparin regulates endothelin production through endothelium-derived nitric oxide in human endothelial cells.
Authors: K Yokokawa, H Tahara, M Kohno, A K Mandal, M Yanagisawa, T Takeda
Journal: Journal of Clinical Investigation (1993)

Heparin shows blood pressure lowering effect in hypertensive patients and animal models. The present study examined the effect of heparin on vasoconstrictor endothelin-1 (ET-1) production in cultured human umbilical vein endothelial cells (ECs) to elucidate the mechanism of antihypertensive effect of heparin. Heparin suppressed both basal and thrombin-stimulated ET-1 mRNA expression paralleled with a decrease in ET-1 peptide release in a dose-dependent manner. Heparin concomitantly enhanced nitric oxide (NO) formation measured by NO2/NO3 levels and cGMP production in ECs. These enhancements were more marked when ECs were stimulated by thrombin. However, these heparin's effects were blunted in the presence of endothelium-derived nitric oxide (EDNO) synthesizing inhibitor NG-monomethyl L-arginine. Therefore, these results suggest that suppression of ET-1 production by heparin is EDNO mediated.
Unusual Case of Meningococcal Septicaemia
Authors: J. J. Linehan
Journal: BMJ (1948)

MEDICALTISHURNAL 27believe she was pregnant.Reckoning, somewhat academically be it admitted in view of this particular patient's irregular menstrua- tion, on a 28-day cycle and a missed period, the date of onset coincided with the probable time of ovulation in the new cycle.Examination under anaesthesia was carried out.Nothing definite could be felt, but an impression was received of a vague soft swell- ing in the left fornix.Needling of the posterior fornix was con- templated but not undertaken, as the finding of blood in such a case would not have further clarified the diagnosis.The abdomen was opened under curarine and cyclopropane anaesthesia.A moderate amount of free blood was found in the pelvis.The uterus appeared normal in size and consistency.The left ovary was found to have a ruptured follicle which appeared to have been about the size of a marble.A half-handful of blood clot was adherent to this.Immediately adjacent was a dark swelling occupying approximately the base of what had been the follicle.A light prick of the scalpel showed the yellow convolutions of a recent corpus luteum.It seemed impossible to say whether one was dealing with one or two structures-a cystic corpus luteum of preg- nancy or a ruptured Graafian follicle adjacent to a recent corpus luteum.The other ovary was normal in appearance.Apart from removing the blood clot and making sure that bleeding had ceased, nothing was done and the abdomen was closed.Next morning a specimen of urine was taken for an Aschheim- Zondek test.On the third day the patient announced that she was menstruating.She had a painless loss, which ceased after four days.The Aschheim-Zondek test was reported weakly positive.Such a result can be obtained immediately before the onset of menstruation.In view of the events outlined it was thus interpreted at first.Two days later bleeding per vaginam was resumed and was followed by slight brownish discharge which continued.Finally on Aug. 8 curettage was undertaken and fragments of an early ovum were found in process of extrusion.Histological examination confirmed the presence of chorionic villi.Recovery thereafter was uneventful.The events subsequent to laparotomy make it clear that the- emergency had been due to rupture of the corpus luteum of pregnancy.Whether or not this had been cystic it is impossible to say, as the normal size is known to have wide variations.It seems likely, though not necessarily conclusive, that the abortion was attributable to the impairment of the integrity of the corpus luteum from traumatic rupture.
Implantable left ventricular assist systems (LVAS): Recent results. A report from a series of meetings sponsored by the Study Group on Advanced Heart Failure of the Working Group on Heart Failure
Authors: Paul Mohacsi, Mario C. Deng, Richard Murphy, Claes‐Håkan Bergh, Edoardo Gronda, Michel Komajda, Richard Pacher, Jindrich Spinar, Karl Swedberg, John F. Cleland
Journal: European Journal of Heart Failure (2000)
A way forward
Authors: Mayur Lakhani
Journal: BMJ (2005)

Revalidation is a summative assessment and must be seen as separate from appraisal and clinical governanceThe General Medical Council's proposals for recertifying doctors in the United Kingdom every five years have been thrown into confusion.A recent judicial inquiry into the case of Harold Shipman, who murdered at least 215 patients, found that the method for revalidating doctors based on regular appraisal would not detect poorly performing doctors. 1 The government suspended plans for revalidation and ordered an urgent review led by the chief medical officer. 2 This article gives a proposal for a way forward.Although the article is from general practice, the framework described is applicable to other specialties.
Prevention of hyaline membrane disease.
Authors: L D Courtney
Journal: BMJ (1973)

knowledge of the height and nude weight of the child and ready access to the nomogram itself.These surface area formulae are themselves subject to considerable error and discrepancy.To relate the dose of nalorphine to 1-73 m2 surface area entails further com- plicated mathematics, since not even the most precocious child is likely to have a surface area approaching that figure.Let us leave mathematics to the mathe- maticians and allow clinicians faced with res,piratory depression due to Lomotil to ventilate wit-h oxygen and to give the anti- dote based on the less complicated measurement of body weight.-Iam, etc.,
Symptoms, Pathogeny, Diagnosis, and Treatment of Addisonian Anaemia
Authors: A. T. Todd
Journal: BMJ (1926)

BRms_~~~~~~~~~~_ r EIA ORA from the residue of the broth filtrate titred 1 in 5,000 and 1 in 500.Ani autolysate from an agar culture.not previously manipulated in any way gave ani agglutinationi titre of 1 in 7,000.We have concluded from these results that auitolysates and aggressins are antigenie, not because
The effects of an abrasive agent on normal skin and on photoaged skin in comparison with topical tretinoin
Authors: R. MARKS, S. HILL, S.P. BARTON
Journal: British Journal of Dermatology (2006)

Two studies were designed to assess the effect of abrasive preparations on the skin and to test the specificity of the effect of topical tretinoin in the management of chronic photodamage to the skin. In the first study two abrasive preparations (Brasivol® fine and Brasivol® medium) were compared with white soft paraffin and no treatment in eight volunteer subjects for their effects on the epidermis. The study was conducted over 3 days and measurements were taken of the effects on dansyl chloride‐induced fluorescence to assess desquamation, epidermal thickness, and the tritiated thymidine autoradiographic labelling index. The abrasives were found to increase the desquamation rate significantly and to increase epidermal thickness and the epidermal labelling index compared to white soft paraffin and no treatment. In the second study the effect of one of the abrasive preparations (Brasivol® medium) was compared with 0.05% tretinoin cream (Retin A®) on the photodamaged skin of the dorsal aspects of the forearms of 12 subjects over an 8‐week period. Cutaneous blood flow measured by the laser‐Doppler flowmeter was found to be significantly increased in the abrasive‐treated sites, but there was only a non‐significant trend to increased blood flow in the tretinoin‐treated sites. Measurements of skin thickness using pulsed A‐scan ultrasound demonstrated that both treatments produced significant increases in thickness over the 8‐week period but the increase was greater for the abrasive treated site. Measurements of the skin extensibility at the treated sites were made using a uniaxial extensometer. Forces needed for 30% skin extension were increased in the abrasive‐treated sites only. Measurements of epidermal thickness and of [3H]‐thymidine autoradiographic labelling indices showed greater increases in the abrasivetreated sites than in tretinoin‐treated sites compared to untreated sites, but these increases were not statistically significant. No significant inflammation and no changes in the degree of elastosis or the presence of a'repair zone' were found in any of the post‐treatment biopsies. The results indicate that some of the changes produced in the skin by topical tretinoin that are taken to indicate a specific antiphotoageing effect may not in fact be specific and can be achieved by an abrasive preparation.
Fc receptors in immune thrombocytopenias: a target for immunomodulation?
Authors: Bethan Psaila, James B. Bussel
Journal: Journal of Clinical Investigation (2008)

In autoimmune disease, Fc receptors (FcRs) form the interface between immune effector cells and their antibody-coated targets, and as such are attractive targets for immunomodulatory therapy. In this issue of the JCI, two highly novel studies of Fc-FcR interactions provide new insights into the role of FcRs in immune thrombocytopenia. Asahi et al. utilized a comprehensive platform of immunological assays to examine the mechanism underlying Helicobacter pylori-associated immune thrombocytopenic purpura, and Ghevaert et al. describe a specially designed antibody that saturates binding sites on fetal platelets without initiating FcgammaR-mediated platelet phagocytosis, preventing the binding of pathological maternal anti-HLA antibodies that cause fetomaternal alloimmune thrombocytopenia (see the related articles beginning on pages 2939 and 2929, respectively). These reports illustrate how a remarkably detailed molecular understanding of the FcR network may translate into new therapeutic strategies with high clinical impact.
Expression of hypoxia-inducible carbonic anhydrases in brain tumors
Authors: Martin A. Proescholdt, Christina Mayer, Marion Kubitza, Thomas Schubert, Shu-Yuan Liao, Eric J. Stanbridge, Sergey Ivanov, Edward H. Oldfield, Alexander Brawanski, Marsha J. Merrill
Journal: Neuro-Oncology (2005)

Malignant brain tumors exhibit distinct metabolic characteristics. Despite high levels of lactate, the intracellular pH of brain tumors is more alkaline than normal brain. Additionally, with increasing malignancy, brain tumors display intratumoral hypoxia. Carbonic anhydrase (CA) IX and XII are transmembrane isoenzymes that are induced by tissue hypoxia. They participate in regulation of pH homeostasis by catalyzing the reversible hydration of carbon dioxide. The aim of our study was to investigate whether brain tumors of different histology and grade of malignancy express elevated levels of CA IX and XII as compared to normal brain. We analyzed 120 tissue specimens from brain tumors (primary and metastatic) and normal brain for CA IX and XII expression by immunohistochemistry, Western blot, and in situ hybridization. Whereas normal brain tissue showed minimal levels of CA IX and XII expression, expression in tumors was found to be upregulated with increased level of malignancy. Hemangioblastomas, from patients with von Hippel-Lindau disease, also displayed high levels of CA IX and XII expression. Comparison of CA IX and XII staining with HIF-1α staining revealed a similar microanatomical distribution, indicating hypoxia as a major, but not the only, induction factor. The extent of CA IX and XII staining correlated with cell proliferation, as indicated by Ki67 labeling. The results demonstrate that CA IX and XII are upregulated in intrinsic and metastatic brain tumors as compared to normal brain tissue. This may contribute to the management of tumor-specific acid load and provide a therapeutic target.
miR-29b as a Therapeutic Agent for Angiotensin II-induced Cardiac Fibrosis by Targeting TGF-β/Smad3 signaling
Authors: Yang Zhang, Xiao-Ru Huang, Li-Hua Wei, Arthur CK Chung, Cheuk-Man Yu, Hui-Yao Lan
Journal: Molecular Therapy (2014)

Loss of miR-29 is associated with cardiac fibrosis. This study examined the role and therapeutic potential of miR-29 in mouse model of hypertension induced by angiotensin II (AngII). By using microRNA microarray, in situ hybridization, and real-time polymerase chain reaction, we found that AngII-induced cardiac fibrosis in the hypertensive heart and in cultured cardiac fibroblasts were associated with downregulation of miR-29a-c via a Smad3-dependent mechanism. In vitro knockdown of miR-29b enhanced but overexpression of miR-29b inhibited AngII-induced fibrosis, revealing a protective role of miR-29b in cardiac fibrosis in response to AngII. This was further demonstrated in vivo by the ability of overexpressing miR-29b in the mouse heart to prevent AngII-mediated cardiac fibrosis and cardiac dysfunction. Importantly, we also found that restored miR-29b in the established hypertensive heart was capable of blocking progressive cardiac fibrosis and improving cardiac dysfunction, demonstrating a therapeutic potential of miR-29b for chronic heart disease. Further studies revealed that targeting the transforming growth factor (TGF)-β1 coding sequence region, thereby inhibiting TGF-β/Smad3 signaling, could be a new mechanism by which miR-29b inhibited AngII-induced cardiac fibrosis. In conclusion, miR-29b plays a protective role in AngII-mediated cardiac remodeling and may be a therapeutic agent for cardiac fibrosis by targeting the TGF-β/Smad3 pathway. Loss of miR-29 is associated with cardiac fibrosis. This study examined the role and therapeutic potential of miR-29 in mouse model of hypertension induced by angiotensin II (AngII). By using microRNA microarray, in situ hybridization, and real-time polymerase chain reaction, we found that AngII-induced cardiac fibrosis in the hypertensive heart and in cultured cardiac fibroblasts were associated with downregulation of miR-29a-c via a Smad3-dependent mechanism. In vitro knockdown of miR-29b enhanced but overexpression of miR-29b inhibited AngII-induced fibrosis, revealing a protective role of miR-29b in cardiac fibrosis in response to AngII. This was further demonstrated in vivo by the ability of overexpressing miR-29b in the mouse heart to prevent AngII-mediated cardiac fibrosis and cardiac dysfunction. Importantly, we also found that restored miR-29b in the established hypertensive heart was capable of blocking progressive cardiac fibrosis and improving cardiac dysfunction, demonstrating a therapeutic potential of miR-29b for chronic heart disease. Further studies revealed that targeting the transforming growth factor (TGF)-β1 coding sequence region, thereby inhibiting TGF-β/Smad3 signaling, could be a new mechanism by which miR-29b inhibited AngII-induced cardiac fibrosis. In conclusion, miR-29b plays a protective role in AngII-mediated cardiac remodeling and may be a therapeutic agent for cardiac fibrosis by targeting the TGF-β/Smad3 pathway.
New UK guidance on resuscitation calls for open decision making
Authors: S. Mayor
Journal: BMJ (2001)

Decisions about cardiopulmonary resuscitation should be based on open communication between health professionals, the patient, and people close to the patient, taking note of patients' informed decisions and reflecting their best interests, recommends new guidance published for the United Kingdom this week.

The guidance, Decisions Relating to Cardiopulmonary Resuscitation , is a joint statement from the BMA, the Resuscitation Council (UK), and the Royal College of Nursing, setting out legal and ethical standards for planning patient care and decision making in relation to resuscitation.

It acknowledges recent public concern about “do not resuscitate” (DNR) orders after …
Forkhead box protein 3 (FOXP3) hypermethylation is associated with diesel exhaust exposure and risk for childhood asthma
Authors: Kelly J. Brunst, Yuet-Kin Leung, Patrick H. Ryan, Gurjit K. Khurana Hershey, Linda Levin, Hong Ji, Grace K. LeMasters, Shuk-Mei Ho
Journal: Journal of Allergy and Clinical Immunology (2012)
Oxyphenisatin and Jaundice
Authors: Knut Naess
Journal: JAMA (1970)

To the Editor.—  Your journal has recently presented two publications and one editorial concerning the puzzling jaundice seen after the administration of oxyphenisatin acetate, which seem to have taken the cause-effect relationship for granted ( 211 :83-85, 86-90,1970).  This cathartic has been used much more in Europe than in the United States, and as far as I know no complications have previously been described. The discrepancies between the findings in these cases and the lack of similar European cases suggests itself.  The drug used in all six cases was not a pure one consisting of the single constituent, oxyphenisatin, but a mixture of this substance with sodium methyl cellulose and dioctyl sodium sulfosuccinate. Of these two compounds, methyl cellulose is surely innocent.  But what do we know about dioctyl sodium sulfosuccinate? Most textbooks describe this only as a wetting agent, which is not absorbed from the intestinal tract. I do not
Psychiatry and Medicine, 1973
Authors: JOHN ROMANO
Journal: Annals of Internal Medicine (1973)

Major changes have occurred since World War I in both the place of psychiatry in medical education and the education of the psychiatrist. The number of psychologists and their kinds of service have grown. The concerns of psychiatry are shifting from the problems of neurosis to those of psychosis and those in the community. Psychiatry has gained more responsibility for care in general hospitals. More conceptual models now offer a wider theoretical base for research and care. Some current developments may be going in the wrong direction, but today's crisis offers chances for fruitful new developments.
Serum 25-Hydroxyvitamin D Levels and Prediabetes Among Subjects Free of Diabetes
Authors: Anoop Shankar, Charumathi Sabanayagam, Sita Kalidindi
Journal: Diabetes Care (2011)

OBJECTIVE Animal studies suggest that low serum 25-hydroxyvitamin D (25[OH]D) may impair insulin synthesis and secretion and be involved in the pathogenesis of diabetes. Results in studies in humans have not been consistent, however. Prediabetes is a stage earlier in the hyperglycemia/diabetes continuum where individuals are at increased risk of developing diabetes and where prevention efforts have been shown to be effective in delaying or preventing the onset of diabetes. However, previous studies have not examined the association between low serum 25(OH)D levels and prediabetes. RESEARCH DESIGN AND METHODS We examined the 12,719 participants (52.5% women) in the third National Health and Nutrition Examination Survey aged &amp;gt;20 years who were free of diabetes. Serum 25(OH)D levels were categorized into quartiles (≤17.7, 17.8–24.5, 24.6–32.4, &amp;gt;32.4 ng/mL). Prediabetes was defined as a 2-h glucose concentration of 140–199 mg/dL, or a fasting glucose concentration of 110–125 mg/dL, or an A1C value of 5.7–6.4%. RESULTS Lower serum 25(OH)D levels were associated with prediabetes after adjusting for age, sex, race/ethnicity, season, geographic region, smoking, alcohol intake, BMI, outdoor physical activity, milk consumption, dietary vitamin D, blood pressure, serum cholesterol, C-reactive protein, and glomerular filtration rate. Compared with quartile 4 of 25(OH)D (referent), the odds ratio of prediabetes associated with quartile 1 was 1.47 (95% CI 1.16–1.85; P = 0.001 for trend). Subgroup analyses examining the relation between 25(OH)D and prediabetes by sex, BMI, and hypertension categories also showed a consistent positive association. CONCLUSIONS Lower serum 25(OH)D levels are associated with prediabetes in a representative sample of U.S. adults.
THE APPLICATION OF THE AMBULANT METHOD IN FRACTURE OF THE LEG IN CHILDREN.
Authors: JAMES PORTER FISKE
Journal: JAMA (1897)

I wish to call attention to the possibility of applying the ambulant method to leg fractures in children, and to discuss the method used and results obtained in fractures occurring in children from the age when they first begin to walk up to the age of puperty, say 14 years. This was discussed, in a measure, by the writer at the New York Academy of Medicine, Jan. 11, 1897, and reported in the<i>Medical News</i>Feb. 13, 1897. When we consider how trying a long confinement is to the young and growing child, how rapidly a general muscular atrophy develops, how easily the onset of anemia presents itself, how insidiously a latent cachexia may develop, the possibility of auto-infection occurring at the site of trauma, we realize to some extent the risks of keeping our fracture cases in bed. A method which admits of a child with a broken leg
Types of Pacemakers
Authors: Victor Parsonnet
Journal: JAMA (1969)

<h3>To the Editor:—</h3> Two different types of pacemakers have been built that avoid competition between the electrical impulse and idiocardiac contractions. One of these is the "standby" pacemaker (of which there are two models). We had the privilege of publishing our first experience with this pacemaker inThe Journal, and subsequently elaborated on this experience elsewhere.<sup>1-3</sup>At the same time others developed a "demand" pacemaker.<sup>4</sup> The article by Goetz (<b>205</b>:657, 1968) as well as your editorial, "Apace With Pacemakers," continued to refer to demand pacemakers without reference to "standby" pacemakers, as if the two were somehow different and unrelated. Despite the slight difference in mode of operation of "standby" and "demand" units, the distinction between them is largely semantic. In both cases a spontaneous idioventricular contraction will affect the next scheduled pacemaker impulse to prevent the implanted pacemaker from firing a stimulus into the vulnerable period of
An inexpensive method of determining body composition by underwater weighing.
Authors: B. A. Clark, J. L. Mayhew
Journal: British Journal of Sports Medicine (1980)

A simple inexpensive densiometric method of determining body composition was compared to a more sophisticated one. Body density (Db), lean body mass (LBM), and relative fat content (%fat) were determined for 16 volunteers, 9 men and 7 women using a simple T-bar apparatus suspended in a swimming pool, and an electronic apparatus in conjunction with a metal tank. Residual volumes (RV) used in the determinations were estimated from age and height (RV-1), held constant at 1,300 ml for men and 1.000 ml for women (RV-2), and measured by the nitrogen washout method (RV-3). No significant difference was observed between the two methods of weighing, although significant differences did exist among the RV techniques. It was concluded that a simplified method of determining body composition is acceptable for screening purposes, but long term studies might require more sophisticated techniques with RV measured at the time of weighing.