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991.
992.
Yukinori Hirota Malcolm Gefter Leonard Mindich 《Proceedings of the National Academy of Sciences of the United States of America》1972,69(11):3238-3242
A mutant of E. coli defective in DNA polymerase II activity was isolated. Extracts had about 0.1% of the normal activity of the DNA polymerase. The effect of the mutation on the ability of cells to replicate DNA of various sources was analyzed. Mutant bacteria grow normally, at 41 degrees as well as at 30 degrees . All bacteriophages, F factors, and R factors examined so far grow normally in the mutant. Sensitivity of the mutant to ultraviolet radiation and alkylating reagents in growth media was the same as that of the wild type.The mutation, polB1, is recessive with respect to wild type. The polB1 mutation can coexist with recombination-defective mutations. Genetic mapping studies show the mutation to be located at about 2 min on the E. coli map. 相似文献
993.
Jaya Chandrasekhar Usman Baber Samantha Sartori Melissa Aquino Annapoorna S. Kini Sunil Rao William Weintraub Timothy D. Henry Serdar Farhan Birgit Vogel Sabato Sorrentino Zhen Ge Samir Kapadia Joseph B. Muhlestein Sandra Weiss Craig Strauss Catalin Toma Anthony DeFranco Roxana Mehran 《The Canadian journal of cardiology》2018,34(3):319-329
Background
Potent P2Y12 inhibitors might offer enhanced benefit against thrombotic events in complex percutaneous coronary intervention (PCI). We examined prasugrel use and outcomes according to PCI complexity, as well as analyzing treatment effects according to thienopyridine type.Methods
PROMETHEUS was a multicentre observational study that compared clopidogrel vs prasugrel in acute coronary syndrome patients who underwent PCI (n = 19,914). Complex PCI was defined as PCI of the left main, bifurcation lesion, moderate-severely calcified lesion, or total stent length ≥ 30 mm. Major adverse cardiac events (MACE) were a composite of death, myocardial infarction, stroke, or unplanned revascularization. Outcomes were adjusted using multivariable Cox regression for effect of PCI complexity and propensity-stratified analysis for effect of thienopyridine type.Results
The study cohort included 48.9% (n = 9735) complex and 51.1% (n = 10,179) noncomplex patients. Second generation drug-eluting stents were used in 70.1% complex and 66.2% noncomplex PCI patients (P < 0.0001). Complex PCI was associated with greater adjusted risk of 1-year MACE (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.20-1.39; P < 0.001). Prasugrel was prescribed in 20.7% of complex and 20.1% of noncomplex PCI patients (P = 0.30). Compared with clopidogrel, prasugrel significantly decreased adjusted risk for 1-year MACE in complex PCI (HR, 0.79; 95% CI, 0.68-0.92) but not noncomplex PCI (HR, 0.91; 95% CI, 0.77-1.08), albeit there was no evidence of interaction (P interaction = 0.281).Conclusions
Despite the use of contemporary techniques, acute coronary syndrome patients who undergo complex PCI had significantly higher rates of 1-year MACE. Adjusted magnitude of treatment effects with prasugrel vs clopidogrel were consistent in complex and noncomplex PCI without evidence of interaction. 相似文献994.
BACKGROUND: Small bowel adenocarcinoma is an uncommon complication of Crohn's disease. We sought to describe the clinical features, outcomes, and risk factors of small bowel adenocarcinoma in Crohn's disease. METHODS: A centralized diagnostic index identified all patients with Crohn's disease with small bowel adenocarcinoma evaluated at our institution between 1976 and 2000, and the medical records were abstracted. Two controls with Crohn's disease were selected for each case, matched by gender and age. RESULTS: Nine cases (four males) were identified. The patients presented with abdominal pain (89%), obstruction (89%), and weight loss (78%). Cancer was located in the ileum in 8 patients (89%) and the jejunum in 1 patient (11%). All cases but 1 had either lymph node involvement or metastasis. All cases had surgery, with 1 receiving adjuvant chemotherapy. No significant risk factors were found. The mortality rates at 1 and 2 years were 42% and 61%. CONCLUSIONS: Small bowel adenocarcinoma is a rare complication of Crohn's disease that typically involves the ileum. Affected patients have symptomatic, advanced malignancies upon diagnosis. No significant risk factors were identified. 相似文献
995.
Dr. Walter A. Koltun M.D. Robert J. Smith M.D. Donna Loehner R.N. Mr. Paul Durdey M.S. F.R.C.S. John A. Coller M.D. John J. Murray M.D. Patricia L. Roberts M.D. Malcolm C. Veidenheimer M.D. Dr. David J. Schoetz Jr. M.D. 《Diseases of the colon and rectum》1993,36(10):922-926
PPURPOSE: The physiologic changes that occur when the small bowel is used as a reservoir, as in the ileal pouchanal anastomosis, are poorly understood. Alterations in bowel permeability, which may lead to bacterial translocation that could result in illness or dysfunction of the pouch, may be one such consequence of the pouch procedure. METHODS: Whole-bowel permeability was evaluated in patients with and without the pouch through the use of an orally consumed nonmetabolizable sugar clearance technique. Patients in whom the ileal pouchanal anastomosis was performed for ulcerative colitis (17 patients) and patients with familial polyposis (7 patients) were compared with normal healthy volunteers (10 patients) and patients with ulcerative colitis with and without curative colectomy and ileostomy (6 and 5 patients, respectively). RESULTS: Measured by this technique, no differences were noted in bowel permeability between the volunteers and patients with ulcerative colitis, even after colectomy and ileostomy (1.7±0.4 in normal healthy volunteers, 1.8±0.5 in patients with ulcerative colitis without stoma, and 1.4±0.2 in patients with ulcerative colitis with ileostomy). The group of patients with an ileal reservoir, however, had a significantly increased index of measured bowel permeability (3.5±0.5 in patients with ulcerative colitis and 5.1±0.7 in patients with familial polyposis;
P<0.05 by analysis of variance compared with normal healthy volunteers and patients with ulcerative colitis with or without ileostomy). CONCLUSION: The exact site, cause, and consequence of this possible alteration of bowel permeability are unclear but appear to be related to the presence of the pouch and are not caused by the underlying pathologic diagnosis.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, May 12 to 17, 1991. Winner of the New Jersey Society of Colon and Rectal Surgeons Award, 1991. 相似文献
996.
A DNA-Unwinding Protein Isolated from Escherichia coli: Its Interaction with DNA and with DNA Polymerases 总被引:42,自引:34,他引:42 下载免费PDF全文
Nolan Sigal Hajo Delius Thomas Kornberg Malcolm L. Gefter Bruce Alberts 《Proceedings of the National Academy of Sciences of the United States of America》1972,69(12):3537-3541
A DNA-unwinding protein has been purified to homogeneity from E. coli. This protein has a molecular weight of about 22,000, as judged by its electrophoretic mobility on polyacrylamide gels containing sodium dodecylsulfate, and it appears to be present in about 800 copies per log-phase cell. It binds tightly and cooperatively to single-stranded DNA, and much less tightly, if at all, to RNA or double-stranded DNA.Like the T4 gene-32 protein characterized previously, the E. coli DNA-unwinding protein depresses the melting temperature of double-stranded DNAs, with regions rich in A-T base-pairs being preferentially melted. The E. coli protein strongly stimulates in vitro DNA synthesis by E. coli DNA polymerase II on appropriate templates; however, no stimulation is found with purified polymerases I or III of E. coli, or with T4 DNA polymerase. In contrast, gene-32 protein stimulates only the T4 DNA polymerase in a parallel assay. 相似文献
997.
998.
Phosphorylation of histone H3 at serine 10 is correlated with chromosome condensation during mitosis and meiosis in Tetrahymena 总被引:10,自引:0,他引:10 下载免费PDF全文
Yi Wei Craig A. Mizzen Richard G. Cook Martin A. Gorovsky C. David Allis 《Proceedings of the National Academy of Sciences of the United States of America》1998,95(13):7480-7484
H3 phosphorylation has been correlated with mitosis temporally in mammalian cells and spatially in ciliated protozoa. In logarithmically growing Tetrahymena thermophila cells, for example, H3 phosphorylation can be detected in germline micronuclei that divide mitotically but not in somatic macronuclei that divide amitotically. Here, we demonstrate that micronuclear H3 phosphorylation occurs at a single site (Ser-10) in the amino-terminal domain of histone H3, the same site phosphorylated during mitosis in mammalian cells. Using an antibody specific for Ser-10 phosphorylated H3, we show that, in Tetrahymena, this modification is correlated with mitotic and meiotic divisions of micronuclei in a fashion that closely coincides with chromosome condensation. Our data suggest that H3 phosphorylation at Ser-10 is a highly conserved event among eukaryotes and is likely involved in both mitotic and meiotic chromosome condensation. 相似文献
999.
Suppressor screen in Mpl-/- mice: c-Myb mutation causes supraphysiological production of platelets in the absence of thrombopoietin signaling 下载免费PDF全文
Carpinelli MR Hilton DJ Metcalf D Antonchuk JL Hyland CD Mifsud SL Di Rago L Hilton AA Willson TA Roberts AW Ramsay RG Nicola NA Alexander WS 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(17):6553-6558
Genetic screens in lower organisms, particularly those that identify modifiers of preexisting genetic defects, have been used successfully to order components of complex signaling pathways. To date, similar suppressor screens have not been used in vertebrates. To define the molecular pathways regulating platelet production, we have executed a large-scale modifier screen with genetically thrombocytopenic Mpl(-/-) mice by using N-ethyl-N-nitrosourea mutagenesis. Here we show that mutations in the c-Myb gene cause a myeloproliferative syndrome and supraphysiological expansion of megakaryocyte and platelet production in the absence of thrombopoietin signaling. This screen demonstrates the utility of large-scale N-ethyl-N-nitrosourea mutagenesis suppressor screens in mice for the simultaneous discovery and in vivo validation of targets for therapeutic discovery in diseases for which mouse models are available. 相似文献
1000.
Treatment of nasopharyngeal carcinoma with Epstein-Barr virus--specific T lymphocytes 总被引:15,自引:0,他引:15 下载免费PDF全文
Straathof KC Bollard CM Popat U Huls MH Lopez T Morriss MC Gresik MV Gee AP Russell HV Brenner MK Rooney CM Heslop HE 《Blood》2005,105(5):1898-1904
Conventional treatment for nasopharyngeal carcinoma (NPC) frequently fails and is accompanied by severe long-term side effects. Since virtually all undifferentiated NPCs are associated with Epstein-Barr virus (EBV), this tumor is an attractive candidate for cellular immunotherapy targeted against tumor-associated viral antigens. We now demonstrate that EBV-specific cytotoxic T-cell (CTL) lines can readily be generated from individuals with NPC, notwithstanding the patients' prior exposure to chemotherapy/radiation. A total of 10 patients diagnosed with advanced NPC were treated with autologous CTLs. All patients tolerated the CTLs, although one developed increased swelling at the site of pre-existing disease. At 19 to 27 months after infusion, 4 patients treated in remission from locally advanced disease remain disease free. Of 6 patients with refractory disease prior to treatment, 2 had complete responses, and remain in remission over 11 to 23 months after treatment; 1 had a partial remission that persisted for 12 months; 1 has had stable disease for more than 14 months; and 2 had no response. These results demonstrate that administration of EBV-specific CTLs to patients with advanced NPC is feasible, appears to be safe, and can be associated with significant antitumor activity. 相似文献