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81.
82.
D. Michal Freedman Kenneth P. Cantor Mary H. Ward Kathy J. Helzlsouer 《Archives of environmental & occupational health》2013,68(5):326-329
Nitrate in drinking water has been implicated as a possible risk factor for non-Hodgkin's lymphoma. The authors examined the association between non-Hodgkin's lymphoma and waterborne nitrate through a population-based case-control study of white men in Minnesota. The authors, by linking residential histories with community water records, estimated average long-term exposure to nitrate in drinking water from 1947 to 1975 for 73 cases diagnosed between 1980 and 1982 and for 147 controls who used community water supplies. No association was found between nitrate levels in community water supplies and non-Hodgkin's lymphoma within the range of study exposures (median of highest exposure category = 2.4 mg nitrate/l [range = 0.1-7.2 mg/l]). The findings provide some safety assurance for those who use water systems that have nitrate levels that are less than 2.4 mg/l. 相似文献
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Rashmi Chandra Yu Wang Rafiq A. Shahid Steven R. Vigna Neil J. Freedman Rodger A. Liddle 《The Journal of clinical investigation》2013,123(8):3343-3352
Cholecystokinin (CCK) is a satiety hormone produced by discrete enteroendocrine cells scattered among absorptive cells of the small intestine. CCK is released into blood following a meal; however, the mechanisms inducing hormone secretion are largely unknown. Ingested fat is the major stimulant of CCK secretion. We recently identified a novel member of the lipoprotein remnant receptor family known as immunoglobulin-like domain containing receptor 1 (ILDR1) in intestinal CCK cells and postulated that this receptor conveyed the signal for fat-stimulated CCK secretion. In the intestine, ILDR1 is expressed exclusively in CCK cells. Orogastric administration of fatty acids elevated blood levels of CCK in wild-type mice but not Ildr1-deficient mice, although the CCK secretory response to trypsin inhibitor was retained. The uptake of fluorescently labeled lipoproteins in ILDR1-transfected CHO cells and release of CCK from isolated intestinal cells required a unique combination of fatty acid plus HDL. CCK secretion secondary to ILDR1 activation was associated with increased [Ca2+]i, consistent with regulated hormone release. These findings demonstrate that ILDR1 regulates CCK release through a mechanism dependent on fatty acids and lipoproteins and that absorbed fatty acids regulate gastrointestinal hormone secretion. 相似文献
86.
S B Freedman D R Richmond M Alwyn D T Kelly 《The American journal of cardiology》1986,57(15):1261-1263
From a series of 37 patients with coronary artery spasm and less than 70% diameter narrowing treated initially with verapamil and nitrates, 33 were followed up 41 to 102 months (mean 62). One patient died from carcinoma of the lung and 3 could not be traced. Before diagnosis, 3 had nontransmural myocardial infarction and 10 had either ventricular tachycardia and fibrillation or atrioventricular block. During follow-up there were no cardiac deaths or myocardial infarctions. Asymptomatic periods of more than 3 months occurred in 23 patients during follow-up: 18 with asymptomatic periods of more than 1 year were pain free at the time of study and 5 with asymptomatic periods of 3 to 6 months had infrequent pain. Ten patients had no asymptomatic periods. Symptomatic status at last review was related to initial response to therapy: 13 of 18 patients (72%) currently asymptomatic became asymptomatic with initial therapy compared with 5 of 15 patients (33%) currently experiencing pain (p = 0.06). Twenty-six patients were currently receiving therapy: 22 verapamil, 80 to 640 mg/day (mean 280), 2 nifedipine, 1 diltiazem and amiodarone and 1 isosorbide (15 were receiving additional isosorbide). Twelve patients were not receiving therapy or were receiving very low dosage therapy, including 8 with asymptomatic periods of more than 1 year. Patients with coronary spasm and less than 70% diameter narrowing treated medically have low mortality and morbidity rates over 5-year follow-up. Many have long asymptomatic periods and some may be able to stop therapy indefinitely. 相似文献
87.
Harry Gibbs Ben Freedman Mårten Rosenqvist Saverio Virdone Wael Al Mahmeed Giuseppe Ambrosio A. John Camm Barry Jacobson Carlos Jerjes-Sanchez Gloria Kayani Ali Oto Elizaveta Panchenko Hany Ragy Ajay K. Kakkar 《The American journal of medicine》2021,134(7):893-901.e11
BackgroundAsymptomatic atrial fibrillation is often detected incidentally. Prognosis and optimal therapy for asymptomatic compared with symptomatic atrial fibrillation is uncertain. This study compares clinical characteristics, treatment, and 2-year outcomes of asymptomatic and symptomatic atrial fibrillation presentations.MethodsGlobal Anticoagulant Registry in the Field-Atrial Fibrillation (GARFIELD-AF) is a global, prospective, observational study of newly diagnosed atrial fibrillation with ≥1 stroke risk factors (http://www.clinicaltrials.gov, unique identifier: NCT01090362). Patients were characterized by atrial fibrillation-related symptoms at presentation and the CHA2DS2-VASc score. Two-year follow-up recorded anticoagulation patterns (vitamin K antagonist, direct oral anticoagulants, parenteral therapy) and outcomes (stroke/systemic embolism, all-cause mortality, and bleeding).ResultsAt presentation, of 52,032 eligible patients, 25.4% were asymptomatic and 74.6% symptomatic. Asymptomatic patients were slightly older (72 vs 70 years), more often male (64.2% vs 52.9%), and more frequently initiated on anticoagulation ± antiplatelets (69.4% vs 66.0%). No difference in events (adjusted hazard ratios, 95% confidence interval) for nonhemorrhagic stroke/systemic embolism (1.19, 0.97-1.45), all-cause mortality (1.06, 0.94-1.20), or bleeding (1.02, 0.87-1.19) was observed. Anticoagulation was associated with comparable reduction in nonhemorrhagic stroke/systemic embolism (0.59, 0.43–0.82 vs 0.78, 0.65–0.93) and all-cause mortality (0.69, 0.59-0.81 vs 0.77, 0.71-0.85) in asymptomatic versus symptomatic, respectively.ConclusionsMajor outcomes do not differ between asymptomatic and symptomatic atrial fibrillation presentations and are comparably reduced by anticoagulation. Opportunistic screening-detected asymptomatic atrial fibrillation likely has the same prognosis as asymptomatic atrial fibrillation at presentation and likely responds similarly to anticoagulation thromboprophylaxis. 相似文献
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Recent studies suggest that lymphoid blast crisis cells of chronic myelogenous leukemia (CML) expressing the common acute lymphoblastic leukemia antigen (CALLA) are B precursor cells, based on the demonstration of immunoglobulin (Ig) gene rearrangement similar to common acute lymphocytic leukemia. There is little evidence to suggest whether the cells with similar lymphoid characteristics in the mixed blast crisis of CML are also committed to B cell lineage. A patient in "mixed" blast crisis of CML was studied. On the basis of morphology, cytochemistry, and immunological studies, the blasts were classified as having either lymphoid or myeloid characteristics. A proportion of the leukemic blasts expressed CALLA, whereas others expressed My7 antigen. In order to characterize both populations of cell further, CALLA+ blasts and My7+ (myeloid) blasts were isolated by fluorescence-activated cell sorting. The My7+ cells were highly proliferative in cell culture blast colony assays, retained the Ph1 chromosome, and were indistinguishable from acute myelogenous leukemia blasts. The CALLA+ cells were also Ph1-chromosome positive, but in contrast, were poorly proliferative in vitro. Of particular note was their retention of germline configuration of Ig genes, thus distinguishing them from blasts in the lymphoid crisis of CML. We conclude that the lymphoid component in mixed blast crisis may represent a stage of differentiation prior to commitment to B lineage. 相似文献
89.
Left coronary artery spasm causing severe left ventricular dysfunction without myocardial infarction
Freedman RJ Fuentes F Smalling RW Kirkeeide RL Sterling RP Walker WE Gould KL 《Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital》1986,13(2):223-231
This report describes a patient with persistent, recurrent left anterior descending coronary artery spasm, which causes marked left ventricular dysfunction in a clinical course that is typical of acute myocardial infarction with hyperacute electrocardiographic changes. However, after emergency coronary artery bypass surgery, the patient had complete reversal of left ventricular dysfunction, with no residual evidence of acute myocardial infarction by electrocardiograph or gated blood pool imaging and no CPK enzyme rise. The patient therefore demonstrates that coronary spasm in some instances clearly precedes the sequence of pathophysiologic events leading to acute myocardial infarction. Our report also demonstrates for the first time in man that massive left ventricular dysfunction may occur in this intermediate coronary syndrome, presenting clinically as impending myocardial infarction. With aggressive surgical intervention and emergency bypass surgery, left ventricular function was restored to normal. Despite the semantic problems of categorizing such patients as having impending myocardial infarction, the severe left ventricular dysfunction and alarming course of this patient's illness was resolved by emergency surgery, suggesting that, in some instances, aggressive therapy is warranted. 相似文献
90.
Monoclonal antibodies reveal receptor specificity among G-protein-coupled receptor kinases. 总被引:2,自引:0,他引:2 下载免费PDF全文
M Oppermann M Diversé-Pierluissi M H Drazner S L Dyer N J Freedman K C Peppel R J Lefkowitz 《Proceedings of the National Academy of Sciences of the United States of America》1996,93(15):7649-7654
Guanine nucleotide-binding regulatory protein (G protein)-coupled receptor kinases (GRKs) constitute a family of serine/threonine kinases that play a major role in the agonist-induced phosphorylation and desensitization of G-protein-coupled receptors. Herein we describe the generation of monoclonal antibodies (mAbs) that specifically react with GRK2 and GRK3 or with GRK4, GRK5, and GRK6. They are used in several different receptor systems to identify the kinases that are responsible for receptor phosphorylation and desensitization. The ability of these reagents to inhibit GRK- mediated receptor phosphorylation is demonstrated in permeabilized 293 cells that overexpress individual GRKs and the type 1A angiotensin II receptor. We also use this approach to identify the endogenous GRKs that are responsible for the agonist-induced phosphorylation of epitope-tagged beta2- adrenergic receptors (beta2ARs) overexpressed in rabbit ventricular myocytes that are infected with a recombinant adenovirus. In these myocytes, anti-GRK2/3 mAbs inhibit isoproterenol-induced receptor phosphorylation by 77%, while GRK4-6-specific mAbs have no effect. Consistent with the operation of a betaAR kinase-mediated mechanism, GRK2 is identified by immunoblot analysis as well as in a functional assay as the predominant GRK expressed in these cells. Microinjection of GRK2/3-specific mAbs into chicken sensory neurons, which have been shown to express a GRK3-like protein, abolishes desensitization of the alpha2AR-mediated calcium current inhibition. The intracellular inhibition of endogenous GRKs by mAbs represents a novel approach to the study of receptor specificities among GRKs that should be widely applicable to many G-protein-coupled receptors. 相似文献