tbuckley/cabot-search huggingface dataset:
Persistent Downregulation of Calcium-Sensing Receptor mRNA in Rat Parathyroids when Severe Secondary Hyperparathyroidism Is Reversed by an Isogenic Kidney Transplantation
Authors: Ewa Lewin, Bartolome Garfia, Fernando Luque Recio, Mariano Rodriguez, Klaus Olgaard
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Experimental severe secondary hyperparathyroidism (HPT) is reversed within 1 wk after reversal of uremia by an isogenic kidney transplantation (KT) in the uremic rats. Abnormal parathyroid hormone (PTH) secretion in uremia is related to downregulation of CaR and vitamin D receptor (VDR) in the parathyroid glands (PG). The aim of this investigation was to examine the expression of CaR and VDR genes after reversal of uremia and HPT in KT rats. 5/6 nephrectomized rats were kept on a normal or high-phosphorus (hP) diet for 8 wk to induce severe HPT (n = 8 in each group). In another group of seven uremic hP rats, uremia was reversed by an isogenic KT and PG were harvested within 1 wk posttransplant. Plasma urea, creatinine, total calcium, phosphorus, and PTH levels were measured. Parathyroid CaR and VDR mRNA were measured by quantitative PCR. Uremic hP rats had significantly elevated levels of creatinine, urea, and phosphorus (P < 0.001) and developed significant hypocalcemia (plasma calcium 1.83 ± 0.2 mmol/L; P < 0.001) compared with normal control rats. After KT, the levels were normalized from day 3 to 7: creatinine from 0.117 ± 0.016 to 0.050 ± 0.002 mmol/L; urea from 23 ± 4 to 7 ± 0.3 mmol/L; phosphorus from 3.9 ± 0.6 to 1.5 ± 0.06 mmol/L; calcium from 1.8 ± 0.2 to 2.5 ± 0.02 mmol/L. Plasma PTH levels fell from 849 ± 224 to a normal level of 38 ± 9 pg/ml (P < 0.01). In uremic rats on a standard diet, CaR mRNA was similar to that of normal control rats, whereas VDR mRNA was significantly decreased. In uremic rats kept on hP diet, CaR mRNA was significantly decreased to 26 ± 7% of control rats (P = 0.01) and VDR mRNA reduced to 36 ± 11% (P < 0.01). In KT, previously hP uremic rats, both CaR mRNA and VDR mRNA remained severely reduced (CaR, 39 ± 7%; VDR, 9 ± 3%; P < 0.01) compared with normal rats. In conclusion, circulating plasma PTH levels normalized rapidly after KT, despite persisting downregulation of CaR and VDR gene expression. This indicates that upregulation of CaR mRNA and VDR mRNA is not necessary to induce the rapid normalization of PTH secretion from hyperplastic parathyroid glands.
Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data
Authors: Oliver J Ziff, Deirdre A Lane, Monica Samra, Michael Griffith, Paulus Kirchhof, Gregory Y H Lip, Richard P Steeds, Jonathan Townend, Dipak Kotecha
Journal: BMJ (2015)

<b>Objective</b> To clarify the impact of digoxin on death and clinical outcomes across all observational and randomised controlled trials, accounting for study designs and methods. <b>Data sources and study selection</b> Comprehensive literature search of Medline, Embase, the Cochrane Library, reference lists, and ongoing studies according to a prospectively registered design (PROSPERO: CRD42014010783), including all studies published from 1960 to July 2014 that examined treatment with digoxin compared with control (placebo or no treatment). <b>Data extraction and synthesis</b> Unadjusted and adjusted data pooled according to study design, analysis method, and risk of bias. <b>Main outcome measures</b> Primary outcome (all cause mortality) and secondary outcomes (including admission to hospital) were meta-analysed with random effects modelling. <b>Results</b> 52 studies were systematically reviewed, comprising 621 845 patients. Digoxin users were 2.4 years older than control (weighted difference 95% confidence interval 1.3 to 3.6), with lower ejection fraction (33% v 42%), more diabetes, and greater use of diuretics and anti-arrhythmic drugs. Meta-analysis included 75 study analyses, with a combined total of 4 006 210 patient years of follow-up. Compared with control, the pooled risk ratio for death with digoxin was 1.76 in unadjusted analyses (1.57 to 1.97), 1.61 in adjusted analyses (1.31 to 1.97), 1.18 in propensity matched studies (1.09 to 1.26), and 0.99 in randomised controlled trials (0.93 to 1.05). Meta-regression confirmed that baseline differences between treatment groups had a significant impact on mortality associated with digoxin, including markers of heart failure severity such as use of diuretics (P=0.004). Studies with better methods and lower risk of bias were more likely to report a neutral association of digoxin with mortality (P&lt;0.001). Across all study types, digoxin led to a small but significant reduction in all cause hospital admission (risk ratio 0.92, 0.89 to 0.95; P&lt;0.001; n=29 525). <b>Conclusions </b>Digoxin is associated with a neutral effect on mortality in randomised trials and a lower rate of admissions to hospital across all study types. Regardless of statistical analysis, prescription biases limit the value of observational data.
Glycine <b> <i>N</i> </b>-Methyltransferase Tumor Susceptibility Gene in the Benzo(<b> <i>a</i> </b>)pyrene-Detoxification Pathway
Authors: Shih-Yin Chen, Jane-Ru Vivan Lin, Ramalakshmi Darbha, Pinpin Lin, Tsung-Yun Liu, Yi-Ming Arthur Chen
Journal: Cancer Research (2004)

Abstract Glycine N-methyltransferase (GNMT) affects genetic stability by (a) regulating the ratio of S-adenosylmethionine to S-adenosylhomocystine and (b) binding to folate. Based on the identification of GNMT as a 4 S polyaromatic hydrocarbon-binding protein, we used liver cancer cell lines that expressed GNMT either transiently or stably in cDNA transfections to analyze the role of GNMT in the benzo(a)pyrene (BaP) detoxification pathway. Results from an indirect immunofluorescent antibody assay showed that GNMT was expressed in cell cytoplasm before BaP treatment and translocated to cell nuclei after BaP treatment. Compared with cells transfected with the vector plasmid, the number of BaP-7,8-diol 9,10-epoxide-DNA adducts that formed in GNMT-expressing cells was significantly reduced. Furthermore, the dose-dependent inhibition of BaP-7,8-diol 9,10-epoxide-DNA adduct formation by GNMT was observed in HepG2 cells infected with different multiplicities of infection of recombinant adenoviruses carrying GNMT cDNA. According to an aryl hydrocarbon hydroxylase enzyme activity assay, GNMT inhibited BaP-induced cytochrome P450 1A1 enzyme activity. Automated BaP docking using a Lamarckian genetic algorithm with GNMT X-ray crystallography revealed a BaP preference for the S-adenosylmethionine-binding domain of the dimeric form of GNMT, a novel finding of a cellular defense against potentially damaging exposures. In addition to GNMT, results from docking experiments showed that BaP binds readily with other DNA methyltransferases, including HhaI, HaeIII, PvuII methyltransferases and human DNA methyltransferase 2. We therefore hypothesized that BaP-DNA methyltransferase and BaP-GNMT interactions may contribute to carcinogenesis.
Interaction of Dendritic Cells with Skin Endothelium: A New Perspective on Immunosurveillance
Authors: Caroline Robert, Robert C. Fuhlbrigge, J. David Kieffer, Seyoum Ayehunie, Richard O. Hynes, Guiying Cheng, Stephan Grabbe, Ulrich H. von Andrian, Thomas S. Kupper
Journal: The Journal of Experimental Medicine (1999)

The goal of this study was to determine the mechanisms by which dendritic cells (DCs) in blood could interact with endothelium, a prerequisite to extravasation into tissues. Our results indicate that DCs express both HECA-452-reactive and nonreactive isoforms of P-selectin glycoprotein ligand 1 (PSGL-1) and can tether and roll efficiently on E- and P-selectin under flow conditions in vitro. Freshly isolated blood DCs were further observed to roll continuously along noninflamed murine dermal endothelium in vivo. This interaction is strictly dependent on endothelial selectins, as shown by experiments with blocking antibodies and with E- and P-selectin-deficient mice. We hypothesize that DCs in blood are constitutively poised at the interface of blood and skin, ready to extravasate upon induction of inflammation, and we showed that cutaneous inflammation results in a rapid recruitment of DCs from the blood to tissues. We propose that this is an important and previously unappreciated element of immunosurveillance.
Increased Sensitivity of Measurement of Drug Effects in Expert Swimmers
Authors: G M SMITH, M WEITZNER, H K BEECHER
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
THE TREATMENT OF INVOLUTIONAL PSYCHOSES WITH DIETHYL STILBESTROL
Authors: EUGENE DAVIDOFF, E. C. REIFENSTEIN, GERALD L. GOODSTONE
Journal: American Journal of Psychiatry (1943)

1. Large doses of diethyl stilbestrol were administered to 45 women with involutional psychoses. 2. Twenty-seven (60 per cent) were improved, while in a control series of 128 women, only 54 (42 per cent) were improved. 3. (A) The simple cases of involutional psychosis responded well to estrogenic therapy. (B) The cases of moderate severity and those of the mixed type reacted favorably, particularly when adjuvant therapy was employed, but relapses occurred and the degree of improvement was not as marked. (C) The psychotic manifestations in the severe cases were not materially affected. These cases may represent a different clinical entity than the mild cases. (D) Therefore, a therapeutic test with estrogenic substance may possess some diagnostic value in involutional psychoses. 4. Cases of dementia præcox, manic-depressive psychosis, and chronic psychoneurosis occurring during the involutional period were not favorably influenced by estrogenic therapy. 5. Diethyl stilbestrol administered orally was about as effective as alpha estradiol injected intramuscularly. About half of those who were given the former preparation exhibited some form of toxic reaction which for the most part did not seriously interfere with the treatment régime. Both substances produced similar psychologic effects. 6. It is concluded that adequate estrogenic therapy has a definite value in the treatment of cases of involutional psychosis of the simple type.
Ensuring Competency in End-of-Life Care
Authors: Charles F. von Gunten, Frank D. Ferris, Linda L. Emanuel
Journal: JAMA (2000)

Physician competence in end-of-life care requires skill in communication, decision making, and building relationships, yet these skills were not taught to the majority of physicians during their training. This article presents a 7-step approach for physicians for structuring communication regarding care at the end of life. Physicians should prepare for discussions by confirming medical facts and establishing an appropriate environment; establish what the patient (and family) knows by using open-ended questions; determine how information is to be handled at the beginning of the patient-physician relationship; deliver the information in a sensitive but straightforward manner; respond to emotions of the patients, parents, and families; establish goals for care and treatment priorities when possible; and establish an overall plan. These 7 steps can be used in situations such as breaking bad news, setting treatment goals, advance care planning, withholding or withdrawing therapy, making decisions in sudden life-threatening illness, resolving conflict around medical futility, responding to a request for physician-assisted suicide, and guiding patients and families through the last hours of living and early stages after death. Effective application as part of core end-of-life care competencies is likely to improve patients' and families' experiences of care. It may also enhance physicians' professional fulfillment from satisfactory relationships with their patients and patients' families.
Defective histamine release in chronic urticaria.
Authors: F Kern, L M Lichtenstein
Journal: Journal of Clinical Investigation (1976)

Histamine release from peripheral blood leukocytes challenged with anti-human IgE was studied in patients with chronic urticaria and nonatopic controls. 19 of 23 controls, but only 6 of 20 patients, released over 20% of the total available leukocyte histamine. The response to anti-IgE concentrations of 1.66, 0.33, 0.066, and 0.013 mug antibody N/ml was significantly lower in patients than in controls. Serum IgE levels were significantly higher in the patients but total histamine content of about 10(7) leukocytes was not. Deuterium oxide (D2O) greatly increased histamine release (in both groups), indicating that the anti-IgE interacted with the basophils of urticaria patients. Passive sensitization of leukocytes with biologically active IgE was achieved in both patients and control subjects whose cells responded to anti-IgE, but was not achieved in either patients or control subjects whose cells were nonresponsive to anti-IgE challenge. 125I-anti-IgE autoradiographic studies revealed no obvious quantitative abnormality in the amount of basophil-bound IgE in chronic urticaria patients. Ionophore stimulation of aliquots of the same leukocytes used for anti-IgE challenge demonstrated that the urticaria patients' basophils were capable of releasing normal amounts of histamine. Leukocyte cyclic AMP levels in the two groups were not significantly different either in base-line levels or in responsiveness to stimulation with isoproterenol. These data indicate that chronic urticaria patients have a (acquired?) defect in leukocyte histamine release that occurs after the anti-IgE-IgE interaction, but before the actual (second-stage) release process, and that is comparable to the phenomenon of desensitization.
Experts devise strategy to fight new TB strain
Authors: Peter Moszynski
Journal: BMJ (2006)

Delegates at a conference in Johannesburg last week drew up a seven point action plan to counter the threat of extensively drug resistant tuberculosis (TB), a newly emergent strain that seems to be resistant to nearly all existing drugs.

The new strain was already present on every continent, but a recent outbreak in South Africa was particularly worrying, experts told the meeting, which was hosted by the South African Medical …
A CASE OF SEVERE HYPERMETABOLISM OF NONTHYROID ORIGIN WITH A DEFECT IN THE MAINTENANCE OF MITOCHONDRIAL RESPIRATORY CONTROL: A CORRELATED CLINICAL, BIOCHEMICAL, AND MORPHOLOGICAL STUDY
Authors: Rolf Luft, Denis Ikkos, Genaro Palmieri, Lars Ernster, Björn Afzelius
Journal: Journal of Clinical Investigation (1962)

ISO.0 0 .* Abbreviations: BMR = basal metabolic rate, PBI = protein-bound iodine.t After triiodothyronine 100 ug daily for 6 days; BMR before +183 per cent and +172 per cent immediately after triiodothyronine.t During i.v.ACTH (25 IU for 8 hours).§ Normal values 2-8.
Written asthma action plans
Authors: M R Partridge
Journal: Thorax (2004)

More widespread use of written asthma action plans should be encouraged

The first British guidelines for the management of asthma in adults published in 1990 clearly recommended self-management of asthma. The exact statement read: “As far as possible, patients should be trained to manage their own treatment rather than be required to consult their doctor before making changes”.1 Similar advice has been repeated in subsequent revisions of the UK guidelines2–4 and in the NHLBI global strategy for asthma management and prevention.5

The evidence base for these recommendations is strong, and 36 trials comparing self-management education with usual care were reviewed for the Cochrane Library.6 This review suggested that self-management education could be associated with a reduction in hospital admissions of up to 40%, a reduction in emergency room visits of 20%, and similarly impressive reductions in unscheduled visits to the doctor, night time symptoms, and days off work or school. The authors concluded that training programmes that enabled people to adjust their medication using a written asthma action plan appeared to be more effective than other forms of self-management. In this issue of Thorax Gibson and Powell7 report the results of a further review to determine what is important about personalised written asthma action plans. They conclude that such plans are best when using 2–4 action points which involve increasing the dose of inhaled steroid and initiation of oral steroid therapy for exacerbations. Plans using peak flow should be based on personal best peak expiratory flow.

The evidence, however, is that—despite a 13 year history of such advice being recommended—implementation of these recommendations is poor. Indeed, in one study of a stratified group of 785 adults and children with asthma, only 3% of respondents had been given a written self-management action plan setting out …
Exercise enhances vasorelaxation in experimental obesity associated hypertension
Authors: P Arvola
Journal: Cardiovascular Research (1999)

Objective: Regular exercise is recommended for the non-pharmacological treatment of hypertension, but the mechanisms underlying the lowering of blood pressure remain controversial. Therefore, we studied the effects of 22-week-long training on blood pressure, arterial reactivity, and metabolic abnormalities in a model of genetic obesity and moderate hypertension. Methods: Obese and lean Zucker rats were subjected to treadmill exercise from 8 to 30 weeks of age. Blood pressures were measured by the tail-cuff method, and urine was collected in metabolic cages. At the end of the study, the samples for biochemical determinations were taken, and reactivity of isolated mesenteric and carotid arterial rings was examined in standard organ chambers. Results: The exercise prevented the elevation of blood pressure which was observed in non-exercised obese Zucker rats, and also reduced blood pressure in the lean rats. The relaxations of norepinephrine-preconstricted mesenteric and carotid arterial rings to acetylcholine and nitroprusside were clearly improved by exercise in the obese rats. In the lean rats exercise enhanced vasorelaxation to nitroprusside in the mesenteric and carotid rings, and to acetylcholine in the carotid preparations. The exercise-induced improvement of endothelium-mediated dilatation to acetylcholine was abolished by nitric oxide synthesis inhibition with NG-nitro-l-arginine methyl ester, but not by cyclooxygenase inhibition with diclofenac or functional inhibition of endothelium-dependent hyperpolarization by precontractions with KCl. The urinary excretion of the systemic prostacyclin metabolite (2,3-dinor-6-ketoprostaglandin F1α) was increased two-fold by exercise in the obese and lean rats, whereas that of the thromboxane A2 metabolite (11-dehydrothromboxane B2) remained unaffected. Treadmill training reduced blood glucose, cholesterol, and triglycerides, but did not affect the high levels of insulin in obese Zucker rats. Conclusions: These results suggest that the antihypertensive effect of long-term exercise in experimental obesity related hypertension is associated with improved vasodilatation. This is expressed as enhanced relaxation via endogenous and exogenous nitric oxide, and increased endothelial prostacyclin production. The improved control of arterial tone after training could be attributed to the alleviation of hyperlipidemia and insulin resistance, whereas hyperinsulinaemia per se remained unaffected.
The limbic basal-ganglia-thalamocortical circuit and goal-directed behavior
Authors: Daphna Joel
Journal: Behavioral and Brain Sciences (1999)

Depue &amp; Collins's model of incentive-motivational modulation of goal-directed behavior subserved by a medial orbital prefrontal cortical (MOC) network is appealing, but it leaves several questions unanswered: How are the stimuli that elicit an incentive motivational state selected? How does the incentive motivational state created by the MOC network modulate behavior? What is the function of the dopaminergic input to the striatum? This commentary suggests possible answers, based on the open-interconnected model of basal-ganglia-thalamocortical circuits, in which the limbic circuit selects goals and, via its connections with the motor and the associative circuits, directs behavior according to those goals, elaborating on the role of dopamine.
Cell-Destructive Activity in the Serum of a Tumor Patient After Infusion of Alkyl Lysophospholipid&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="author-notes" rid="fn3"&gt;3&lt;/xref&gt;
Authors: R Andreesen, P G Munder
Journal: JNCI Journal of the National Cancer Institute (1983)

Sera collected from 1 tumor patient after a 12-hour infusion of 30-50 mg alkyl lysophospholipids (ALP)/kg induced a progressive destruction of human leukemia cells (HL60) in vitro. This cytotoxic serum activity correlated with the dose of ALP administered and was inhibited by the addition of a metabolizable lysophospholipid analogue. Human bone marrow cells and concanavalin A-stimulated lymphoblasts were affected to a much lesser degree, whereas cells of the erythroleukemia line K562 appeared to be relatively resistant. When cells were cultured in postinfusion sera, the cytotoxicity of ALP in vitro was enhanced as much as fifteenfold when compared with the cytotoxicity of ALP when the cells were cultured in normal sera. No change in either relative or absolute distribution of phospholipids in postinfusion sera could be detected.
Advances in the Pathogenesis, Diagnosis, and Treatment of Thrombotic Thrombocytopenic Purpura
Authors: Han-Mou Tsai
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Thrombotic thrombocytopenic purpura (TTP) and the hemolytic uremic syndrome (HUS) are both characterized by thrombocytopenia, microangiopathic hemolysis, and organ dysfunction. Other disorders occasionally present with similar manifestations. Recent studies have demonstrated that deficiency in the von Willebrand factor cleaving protease ADAMTS13, due to genetic mutations or autoimmune inhibitors, causes TTP. Molecular cloning of ADAMTS13 elucidates the structure of the protease, raising the prospect for advances in diagnosis and treatment of the disease. Assay of ADAMTS13 activity distinguishes TTP from HUS and other types of thrombotic microangiopathy (TMA); therefore, the term TTP/HUS should be avoided because it obscures the known or potential differences among the various types of TMA. E-mail: [email protected]
Body mass index as a prognostic feature in operable breast cancer: the International Breast Cancer Study Group experience
Authors: G. Berclaz, S. Li, K.N. Price, A.S. Coates, M. Castiglione-Gertsch, C.-M. Rudenstam, S.B. Holmberg, J. Lindtner, D. Erien, J. Collins, R. Snyder, B. Thürlimann, M.F. Fey, C. Mendiola, I. Dudley Werner, E. Simoncini, D. Crivellari, R.D. Gelber, A. Goldhirsch
Journal: Annals of Oncology (2004)