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1.
Bartonella quintana, the agent of trench fever and a cause of endocarditis and bacillary angiomatosis in humans, has the highest reported in vitro hemin requirement for any bacterium. We determined that eight membrane-associated proteins from B. quintana bind hemin and that a approximately 25-kDa protein (HbpA) was the dominant hemin-binding protein. Like many outer membrane proteins, HbpA partitions to the detergent phase of a Triton X-114 extract of the cell and is heat modifiable, displaying an apparent molecular mass shift from approximately 25 to 30 kDa when solubilized at 100 degrees C. Immunoblots of purified outer and inner membranes and immunoelectron microscopy with whole cells show that HbpA is strictly located in the outer membrane and surface exposed, respectively. The N-terminal sequence of mature HbpA was determined and used to clone the HbpA-encoding gene (hbpA) from a lambda genomic library. The hbpA gene is 816 bp in length, encoding a predicted immature protein of approximately 29.3 kDa and a mature protein of 27.1 kDa. A Fur box homolog with 53% identity to the Escherichia coli Fur consensus is located upstream of hbpA and may be involved in regulating expression. BLAST searches indicate that the closest homologs to HbpA include the Bartonella henselae phage-associated membrane protein, Pap31 (58.4% identity), and the OMP31 porin from Brucella melitensis (31.7% identity). High-stringency Southern blots indicate that all five pathogenic Bartonella spp. possess hbpA homologs. Recombinant HbpA can bind hemin in vitro; however, it does not confer a hemin-binding phenotype upon E. coli. Intact B. quintana treated with purified anti-HbpA Fab fragments show a significant (P < 0.004) dose-dependent decrease in hemin binding relative to controls, suggesting that HbpA plays an active role in hemin acquisition and therefore pathogenesis. HbpA is the first potential virulence determinant characterized from B. quintana. 相似文献
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Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. Results of a Veterans Administration Cooperative Study 总被引:31,自引:0,他引:31
H D Lewis J W Davis D G Archibald W E Steinke T C Smitherman J E Doherty H W Schnaper M M LeWinter E Linares J M Pouget S C Sabharwal E Chesler H DeMots 《The New England journal of medicine》1983,309(7):396-403
We conducted a multicenter, double-blind, placebo-controlled randomized trial of aspirin treatment (324 mg in buffered solution daily) for 12 weeks in 1266 men with unstable angina (625 taking aspirin and 641 placebo). The principal end points were death and acute myocardial infarction diagnosed by the presence of creatine kinase MB or pathologic Q-wave changes on electrocardiograms. The incidence of death or acute myocardial infarction was 51 per cent lower in the aspirin group than in the placebo group: 31 patients (5.0 per cent) as compared with 65 (10.1 per cent); P = 0.0005. Nonfatal acute myocardial infarction was 51 per cent lower in the aspirin group: 21 patients (3.4 per cent) as compared with 44 (6.9 per cent); P = 0.005. The reduction in mortality in the aspirin group was also 51 per cent--10 patients (1.6 per cent) as compared with 21 (3.3 per cent)--although it was not statistically significant; P = 0.054. There was no difference in gastrointestinal symptoms or evidence of blood loss between the treatment and control groups. Our data show that aspirin has a protective effect against acute myocardial infarction in men with unstable angina, and they suggest a similar effect on mortality. 相似文献
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Cognitive‐Behavioral Therapy for Insomnia to Reduce Chronic Migraine: A Sequential Bayesian Analysis 下载免费PDF全文
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Unstable angina pectoris: the first half century: natural history, pathophysiology, and treatment 总被引:1,自引:0,他引:1
T C Smitherman 《The American journal of the medical sciences》1986,292(6):395-406
Unstable angina pectoris as a distinct syndrome intermediate between chronic stable angina and acute myocardial infarction was first described about a half century ago. The incidence of death or myocardial infarction rises in the first few months after destabilization of angina. Hemodynamic, scintigraphic, and arteriographic studies in the last 15 years have shown that unstable angina is chiefly due to "dynamic" coronary stenoses, transient reversible limitations in coronary blood flow caused by a complex interaction between coronary vasoconstriction, transient platelet plugging, and transient thrombosis. The trigger for the onset of dynamic coronary stenoses is probably acute changes in coronary arterial morphology in or near atherosclerotic plaques making those areas more thrombogenic. A large fraction of patients with unstable angina restabilize initially with medical management. The role of beta blockers is unclear, but they may protect against development of coronary events for patients with unstable angina similar to that reported for patients with myocardial infarction. Nitrates and calcium blockers are probably superior to beta blockers in restabilization of angina, but protection against coronary events has not yet been demonstrated clearly. Further investigation is needed to distinguish the relative benefits of a two-drug (heart rate-limiting calcium blocker plus nitrates) regimen vs. a three-drug regimen including beta blocker. There is no basis for emergency coronary bypass surgery to prevent myocardial infarction or death. Urgent surgery should be limited to patients who do not stabilize readily with medical therapy. One third or more of the patients who initially restabilize with medical therapy will require coronary revascularization in the year after unstable angina because of severe angina. An antithrombotic regimen of aspirin (or possibly heparin) reduces the incidence of progression to death or myocardial infarction. Two important future directions for research should be promising: development of better antithrombotic regimens other than aspirin alone for protection against coronary events; and improved ability to distinguish the patients who initially respond to medical therapy who are at low risk for later severe angina from those at higher risk. 相似文献