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991.
Cotsiki M Lock RL Cheng Y Williams GL Zhao J Perera D Freire R Entwistle A Golemis EA Roberts TM Jat PS Gjoerup OV 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(4):947-952
The mitotic spindle checkpoint protein Bub1 has been found to be mutated at low frequency in certain human cancers characterized by aneuploidy. Simian virus 40 large T antigen efficiently immortalizes rodent cells and occasionally transforms them to tumorigenicity. T antigen can also cause genomic instability, inducing chromosomal aberrations and aneuploidy. Here, we report an interaction between Bub1 and T antigen. T antigen coimmunoprecipitates with endogenous Bub1 and Bub3, another component of the spindle checkpoint complex. Genetic analysis demonstrates that the interaction of T antigen with Bub1 is not required for immortalization but is closely correlated with transformation. T antigen induces an override of the spindle checkpoint dependent on Bub1 binding. This interaction with proteins of the spindle checkpoint machinery suggests another role for T antigen and provides insight into its ability to cause chromosomal aberrations, aneuploidy, and transformation. 相似文献
992.
Olson JC Erbey JR Forrest KY Williams K Becker DJ Orchard TJ 《Metabolism: clinical and experimental》2002,51(2):248-254
The purpose of this study was to determine the predictors of lower extremity arterial disease (LEAD) events in a type 1 diabetes population. Data are from the Pittsburgh Epidemiology of Diabetes Complications Study of childhood onset type 1 diabetes. At baseline, the study population had a mean age 28 (range, 8 to 47) years and duration 19 (range, 7 to 37) years. LEAD events, assessed by questionnaire or clinical examination, were defined as claudication (Rose questionnaire), foot ulceration, or lower extremity amputation. Estimated glucose disposal rate (eGDR), a measure of insulin resistance, was calculated from glycosylated hemoglobin (HbA(1)), waist-to-hip ratio (WHR), and hypertension using an equation previously validated with hyperinsulinemic euglycemic clamp studies. There were incident LEAD events in 70 of 586 subjects during 10 years follow-up, giving an incidence density of 1.3 events/100 person-years. Incidence did not differ by gender. Major predictors of LEAD events were diabetes duration, low-density lipoprotein-cholesterol (LDL-C), heart rate, eGDR, log albumin excretion rate (AER), systolic blood pressure (SBP), hypertension, proliferative retinopathy, distal symmetric polyneuropathy, and overt nephropathy (each P <.001). HbA(1), low ankle brachial index (ABI) (<0.9), and a high ankle brachial difference (ABD) (SBP > or = 75 mm Hg) also predicted LEAD events. Cox modeling suggested that duration (P <.001), HbA(1) (P <.001), hypertension (P =.006), log albumin excretion rate (P =.011), and heart rate (P =.028) predicted events independently. The overall model with HbA(1) and hypertension was significantly better than with eGDR, while the alternate models in men were similar. In women, the model with eGDR showed a significantly better fit. Glycemia, insulin resistance, hypertension and renal disease are powerful predictors of symptomatic lower extremity arterial disease in type 1 diabetes. 相似文献
993.
Diabetes self-management education (DSME) has been shown to improve health outcomes. Yet, relatively little is known about
how DSME has its effects. Literature reviewed from the past 3 years indicates that if DSME is to become more effective interventions
need to be theory-based, to increase patient involvement in their care, and to encompass a broader array of evidenced-based
outcomes. Outcomes reviewed go beyond knowledge and glycemic control to include prevention of diabetes, quality of life, and
reduction of cardiovascular risk. The ability of practitioners and health care systems to implement, adopt, and maintain patient-centered
interventions over time is discussed. By linking theory to behavior, and broadening the outcomes examined, advances can continue
to be made in closing the gap between the scientific base for the treatment of diabetes, and the care and outcomes patients
experience. Further research on patient-centered approaches that promote self-management is seen as critical in closing this
gap. 相似文献
994.
Most reported cases of inorganic mercury poisoning are from mercuric chloride. We report a case of mercuric oxide (HgO) powder ingestion. A 31-year-old man presented to an emergency department after ingestion of approximately 40 g of HgO. Soon after ingestion, he developed nausea, vomiting, and abdominal cramping. Abdominal radiograph revealed densely radiopaque material in the stomach. Gastrointestinal decontamination was accomplished with activated charcoal and whole-bowel irrigation with polyethylene glycol solution (Golytely) for 24 hours until repeat abdominal radiographs no longer demonstrated the substance in the gastrointestinal tract. He was also chelated with British anti-Lewisite for 5 days, followed by succimer for 10 days. He had markedly elevated urine and blood mercury levels after ingestion, but except for a mildly depressed serum bicarbonate (19 mEq/L), his chemistry results remained normal including blood urea nitrogen and creatinine. He had an uncomplicated hospital course and remained asymptomatic at 6 months postingestion. Despite elevated urine and blood mercury levels after ingestion of HgO, our patient did not develop the end-organ toxicity typical of inorganic mercury poisoning. 相似文献
995.
Sawitzke AD Shi H Finco MF Dunlop DD Bingham CO Harris CL Singer NG Bradley JD Silver D Jackson CG Lane NE Oddis CV Wolfe F Lisse J Furst DE Reda DJ Moskowitz RW Williams HJ Clegg DO 《Arthritis and rheumatism》2008,58(10):3183-3191
OBJECTIVE: Osteoarthritis (OA) of the knee causes significant morbidity and current medical treatment is limited to symptom relief, while therapies able to slow structural damage remain elusive. This study was undertaken to evaluate the effect of glucosamine and chondroitin sulfate (CS), alone or in combination, as well as celecoxib and placebo on progressive loss of joint space width (JSW) in patients with knee OA. METHODS: A 24-month, double-blind, placebo-controlled study, conducted at 9 sites in the United States as part of the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), enrolled 572 patients with knee OA who satisfied radiographic criteria (Kellgren/Lawrence [K/L] grade 2 or grade 3 changes and JSW of at least 2 mm at baseline). Patients with primarily lateral compartment narrowing at any time point were excluded. Patients who had been randomized to 1 of the 5 groups in the GAIT continued to receive glucosamine 500 mg 3 times daily, CS 400 mg 3 times daily, the combination of glucosamine and CS, celecoxib 200 mg daily, or placebo over 24 months. The minimum medial tibiofemoral JSW was measured at baseline, 12 months, and 24 months. The primary outcome measure was the mean change in JSW from baseline. RESULTS: The mean JSW loss at 2 years in knees with OA in the placebo group, adjusted for design and clinical factors, was 0.166 mm. No statistically significant difference in mean JSW loss was observed in any treatment group compared with the placebo group. Treatment effects on K/L grade 2 knees, but not on K/L grade 3 knees, showed a trend toward improvement relative to the placebo group. The power of the study was diminished by the limited sample size, variance of JSW measurement, and a smaller than expected loss in JSW. CONCLUSION: At 2 years, no treatment achieved a predefined threshold of clinically important difference in JSW loss as compared with placebo. However, knees with K/L grade 2 radiographic OA appeared to have the greatest potential for modification by these treatments. 相似文献
996.
Nazim Uddin Azam Khan M.D. Assad Movahed M.D. Pabitra Kumar Saha M.D. Jaffar Ali Raza M.D. Jaafer Golzar M.D. J. Mark Williams M.D. Rony L. Shammas M.D. 《The International journal of angiology》2005,14(2):94-96
Acute left main coronary artery occlusion is a catastrophic and mostly fatal event. Patients may present with sudden death
or cardiogenic shock. Intra-aortic balloon pump support and emergency revascularization is indicated to preserve the left
ventricular function. We describe a case of left main thrombus in a health 24-year-old young male with no risk factors for
coronary atherosclerosis. 相似文献
997.
Both heterozygous and homozygous alpha+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya 下载免费PDF全文
Although the alpha+ thalassemias almost certainly confer protection against death from malaria, this has not been formally documented. We have conducted a study involving 655 case patients with rigorously defined severe malaria and 648 controls, frequency matched on area of residence and ethnic group. The prevalence of both heterozygous and homozygous alpha+ thalassemia was reduced in both case patients with severe malaria (adjusted odds ratios [ORs], 0.73 and 0.57; 95% confidence intervals [95% CIs], 0.57-0.94 and 0.40-0.81; P = .013 and P = .002, respectively, compared with controls) and among the subgroup of children who died after admission with severe malaria (OR, 0.60 and 0.37; 95% CI, 0.37-1.00 and 0.16-0.87; P = .05 and P = .02, respectively, compared with surviving case patients). The lowest ORs were seen for the forms of malaria associated with the highest mortality-coma and severe anemia complicated by deep, acidotic breathing. Our study supports the conclusion that both heterozygotes and homozygotes enjoy a selective advantage against death from Plasmodium falciparum malaria. 相似文献
998.
999.
Tumour necrosis factor alpha is an important mediator of portal and systemic haemodynamic derangements in alcoholic hepatitis 总被引:10,自引:0,他引:10 下载免费PDF全文
BACKGROUND: The role of proinflammatory cytokines in the pathogenesis of portal hypertension is unclear. AIMS AND METHODS: This study tests the hypothesis that tumour necrosis factor alpha (TNF-alpha) is an important mediator of the circulatory disturbances in alcoholic hepatitis (AH) and evaluates the acute and short term effect of a single infusion of the monoclonal chimeric anti-TNF-alpha antibody (Infliximab) on portal and systemic haemodynamics in 10 patients with severe biopsy proven AH. Cardiovascular haemodynamics, hepatic venous pressure gradient (HVPG), and hepatic and renal blood flow were measured before, 24 hours after Infliximab, and prior to hospital discharge. RESULTS: Serum bilirubin (p<0.05), C reactive protein (p<0.001), and white cell count (p<0.01) were reduced significantly, as were plasma levels of interleukin (IL)-6 and IL-8 after treatment. Of the 10 patients, nine were alive at 28 days. Mean HVPG decreased significantly at 24 hours (23.4 (2.8) to 14.3 (1.9) mm Hg; p<0.001) with a sustained reduction prior to discharge (12.8 (1.9) mm Hg; p<0.001). Mean arterial pressure and systemic vascular resistance increased significantly (p<0.001and p<0.01, respectively), mirrored by a reduction in cardiac index (5.9 (0.5) to 4.7 (0.5) l/min/m(2); p<0.05) prior to discharge. Hepatic and renal blood flow also increased significantly (506.2 (42.9) to 646.3 (49.2) ml/min (p=0.001) and 424.3 (65.12) to 506.3 (85.7) ml/min (p=0.001), respectively) prior to discharge. CONCLUSION: The results of this study illustrate that anti-TNF-alpha treatment in AH patients produces a highly significant, early, and sustained reduction in HVPG, possibly through a combination of a reduction in cardiac output and intrahepatic resistance. In addition, there was a reduction in hepatic inflammation and improved organ blood flow, suggesting an important role for TNF-alpha in mediating the circulatory disturbances in AH. 相似文献
1000.
K R Williams M B LoPresti M Setoguchi W H Konigsberg 《Proceedings of the National Academy of Sciences of the United States of America》1980,77(8):4614-4617
The primary structure of the T4 single-stranded DNA-binding protein coded by gene 32 has been determined by manual and autoated sequencing of peptides derived from partial proteolysis, cyanogen bromide cleavage, and digestion with trypsin, chymotrypsin, and staphylococcal protease. Tryptic digestion of citraconylated or succinylated gene 32 protein yields five peptides containing 4, 27, 42, 65, and 163 residues, which can be separated by Sephadex chromatography. Each of the tryptic peptides was subjected to automated sequencing and, if necessary, more extensive cleavage. The intact protein contains 301 amino acids, has a molecular weight of 33,487, and can be specifically cleaved at lysines 21 and 253 by limited trypsin digestion. Previous studies have shown that the "B" region (residues 1-21), which has a charge of +4, is important for the protein-protein interactions involved in gene 32 protein self-association and cooperaive binding to single-stranded DNA. The "A" region (residues 254-301) has been implicated in controlling the helix-destabilizing "activity" of gene 32 protein and in interacting with other T4 DNA replication proteins. The A region has a charge of -10 and, in addition, contains two unusual stretches of four serine residues separated by glycine 284. The region between positions 73 and 115 contains 75% of the tyrosine residues and may be important for DNA binding. 相似文献