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91.
Stroke following coronary-artery bypass surgery. A case-control estimate of the risk from carotid bruits 总被引:4,自引:0,他引:4
G L Reed D E Singer E H Picard R W DeSanctis 《The New England journal of medicine》1988,319(19):1246-1250
The causes of stroke following coronary-artery bypass surgery are largely unknown. To determine whether carotid bruits increase the risk of these events, we compared 54 patients with postoperative stroke or transient ischemic attacks with 54 randomly selected control patients. Both groups were drawn from 5915 consecutive patients who had coronary bypass surgery at our hospital from 1970 to 1984. Carotid bruits were noted preoperatively in 13 patients with postoperative stroke and in 4 control patients. Case-control analysis showed that the presence of carotid bruits increased the risk of stroke or transient ischemic attacks by 3.9-fold (95 percent confidence interval, 1.2 to 12.8; P less than 0.05). This increased risk remained essentially unchanged after adjustment for potentially confounding variables in a multiple logistic regression analysis. Other factors associated with a significantly increased risk (P less than 0.05) of these neurologic deficits were a history of stroke or transient ischemic attack (odds ratio, 6.0; 95 percent confidence interval, 1.6 to 22.1), a history of congestive heart failure (odds ratio, 5.3; confidence interval, 1.6 to 17.0), mitral regurgitation (odds ratio, 4.3; confidence interval, 1.4 to 12.9), postoperative atrial fibrillation (odds ratio, 3.0; confidence interval, 1.4 to 6.7), a cardiopulmonary-bypass pump time of more than two hours (odds ratio, 2.7; confidence interval, 1.1 to 6.7), and a previous myocardial infarction (odds ratio, 2.3; confidence interval, 1.1 to 5.1). We conclude that the presence of carotid bruits increases the risk of stroke after coronary-artery bypass surgery. However, the absolute magnitude of this risk, 2.9 percent, is small and comparable to the reported risk of stroke from carotid endarterectomy. 相似文献
92.
93.
BAG1 over-expression in brain protects against stroke 总被引:3,自引:0,他引:3
Kermer P Digicaylioglu MH Kaul M Zapata JM Krajewska M Stenner-Liewen F Takayama S Krajewski S Lipton SA Reed JC 《Brain pathology (Zurich, Switzerland)》2003,13(4):495-506
The co-chaperone BAG1 binds and regulates 70 kDa heat shock proteins (Hsp70/Hsc70) and exhibits cytoprotective activity in cell culture models. Recently, we observed that BAG1 expression is induced during neuronal differentiation in the developing brain. However, the in vivo effects of BAG1 during development and after maturation of the central nervous system have never been examined. We generated transgenic mice over-expressing BAG1 in neurons. While brain development was essentially normal, cultured cortical neurons from transgenic animals exhibited resistance to glutamate-induced, apoptotic neuronal death. Moreover, in an in vivo stroke model involving transient middle cerebral artery occlusion, BAG1 transgenic mice demonstrated decreased mortality and substantially reduced infarct volumes compared to wild-type littermates. Interestingly, brain tissue from BAG1 transgenic mice contained higher levels of neuroprotective Hsp70/Hsc70 protein but not mRNA, suggesting a potential mechanism whereby BAG1 exerts its anti-apoptotic effects. In summary, BAG1 displays potent neuroprotective activity in vivo against stroke, and therefore represents an interesting target for developing new therapeutic strategies including gene therapy and small-molecule drugs for reducing brain injury during cerebral ischemia and neurodegenerative diseases. 相似文献
94.
A murine model of bone marrow micrometastasis in breast cancer 总被引:3,自引:0,他引:3
Murphy BO Joshi S Kessinger A Reed E Sharp JG 《Clinical & experimental metastasis》2002,19(7):561-569
Bone marrow (BM) is one of the most common sites and often the first clinical indication of metastatic progression of breast
cancer. Multivariate analyses have shown that the presence of cytokeratin positive tumor cells in the marrow of women with
newly diagnosed stage I, II or III breast cancer is an independent predictor of survival. The objective of this study was
to develop an orthotopic model of spontaneous BM metastasis to facilitate studies of this process. A murine mammary adenocarcinoma
cell line, Clone 66, was transduced with the neomycin resistance gene (Cl66neo) and injected orthotopically into female Balb/c mice. Polymerase chain reaction (PCR) for the neo gene performed on BM cells
harvested from tumor bearing mice demonstrated as few as 102 injected tumor cells produced BM micrometastases at 4 weeks post-injection. Small foci of tumor cells were identified in
the mammary fatpad (mfp) without gross evidence of primary tumors. Higher doses of tumor cells produced BM micrometastases,
detectable by PCR, at one week post-injection. Constructs containing green fluorescent protein (GFP) and the neomycin resistance
gene (neo) were also transduced into Clone 66 cells (Cl66-GFPneo) and injected into the mfp. GFP transduced tumor cells were identified in multiple tissues in addition to BM by flow cytometric
analysis (FACS) but less 13% of the animals developed gross metastases. This model is a clinically relevant tool for the analysis
of organ specificity of metastasis.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
95.
We have cloned four cyclin-B homologs from Saccharomyces cerevisiae, CLB1-CLB4, using the polymerase chain reaction and low stringency hybridization approaches. These genes form two classes based on sequence relatedness: CLB1 and CLB2 show highest homology to the Schizosaccharomyces pombe cyclin-B homolog cdc13 involved in the initiation of mitosis, whereas CLB3 and CLB4 are more highly related to the S. pombe cyclin-B homolog cig1, which appears to play a role in G1 or S phase. CLB1 and CLB2 mRNA levels peak late in the cell cycle, whereas CLB3 and CLB4 are expressed earlier in the cell cycle but peak later than the G1-specific cyclin, CLN1. Analysis of null mutations suggested that the CLB genes exhibit some degree of redundancy, but clb1,2 and clb2,3 cells were inviable. Using clb1,2,3,4 cells rescued by conditional overproduction of CLB1, we showed that the CLB genes perform an essential role at the G2/M-phase transition, and also a role in S phase. CLB genes also appear to share a role in the assembly and maintenance of the mitotic spindle. Taken together, these analyses suggest that CLB1 and CLB2 are crucial for mitotic induction, whereas CLB3 and CLB4 might participate additionally in DNA replication and spindle assembly. 相似文献
96.
Previous research indicates that rats fed a high-fat (HF) diet increase their intake and preference for oil compared with rats fed a high-carbohydrate (HC) diet. To assess whether this increased intake was due to the sensory or postingestive properties of oil, rats were adapted to either the HF or HC diet and then allowed to sham-feed pure corn oil daily for 30 min. During the first 4 trials, rats fed the HF diet sham-fed more oil than did rats fed the HC diet; however, this difference diminished with repeated testing and was absent after 8 trials. In both diet groups, 4-5 calories (approximately 25%) of sham-fed oil could not be recovered and may have escaped to the intestine. These results suggest that, compared with rats fed a HC diet, rats fed a HF diet are initially attracted to the sensory properties of oil, but that the differential oil intakes of rats fed the HF or HC diet are maintained by postingestive, rather than sensory factors. 相似文献
97.
A genome-wide scan suggests a locus on chromosome 1q21-q23 contributes to normal variation in plasma cholesterol concentration 总被引:3,自引:0,他引:3
Reed DR Nanthakumar E North M Bell C Price RA 《Journal of molecular medicine (Berlin, Germany)》2001,79(5-6):262-269
To identify genes that influence plasma cholesterol, triglyceride, and high-density and low-density lipoproteins concentrations we conducted a genome-wide scan using 354 polymorphic markers spaced at 10-cM intervals in 75 obese but otherwise normal human families. The results of the genome scan using sibling pair analysis of quantitative phenotypes suggested that 1q21-q23 contains a locus that influences plasma cholesterol concentration. Chromosome 12 gave evidence of linkage to plasma triglyceride concentration (D12SPAH) and chromosomes 3, 6, 7, 10, 11, 17, and 20 yielded additional evidence of linkage for lipid phenotypes at lower levels of statistical significance. Allele sharing for markers near prominent candidate genes was either very weakly related or unrelated to sibling similarity for lipid concentrations. Together these results suggest that genes with important roles in regulating normal cholesterol and triglyceride concentrations do not coincide with the location of previously known candidate genes. 相似文献
98.
Fumino Iwata Ernest M. Kuehl George F. Reed Lessie M. McCain William A. Gahl Muriel I. Kaiser-Kupfer 《Molecular genetics and metabolism》1998,64(4):237-242
In nephropathic cystinosis, corneal cystine crystals cause severe photophobia and corneal erosions. Topical cysteamine dissolves these crystals, but cannot be marketed because it rapidly oxidizes to the disulfide form, cystamine, at room temperature. Since cystamine itself could be used commercially, we compared the efficacy of cystamine and cysteamine with respect to cystine crystal dissolution in a randomized, double-masked clinical trial. One eye each of 14 patients with cystinosis was randomized to either cystamine or cysteamine, 0.5%, with 0.01% benzalkonium chloride; the companion eye was treated with the alternate preparation. Corneal crystals were photographed and a density score was assigned to each slide based on 13 standard slides. After 8–20 months, 6 patients showed significant reduction of the corneal crystal score in only one eye. In each case, the improved eye was the cysteamine-treated eye. Theoretically, cysteamine should dissolve both intracellular and extracellular crystals, whereas cystamine should dissolve only intracellular crystals because it must first be reduced to the free thiol by the cytoplasmic-reducing environment. Hence, the lack of efficacy of the disulfide cystamine suggests that some corneal cystine crystals in cystinosis patients are extracellular, and that another form of stable, topical cysteamine must be developed for cystinosis patients. 相似文献
99.
Granulocyte/macrophage colony stimulating factor. A potent activation signal for mature macrophages and monocytes 总被引:3,自引:0,他引:3
P J Morrissey K H Grabstein S G Reed P J Conlon 《International archives of allergy and applied immunology》1989,88(1-2):40-45
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a well-characterized hematopoietic growth factor. Recently, using purified recombinant-derived material, we have found that GM-CSF is also a potent activator of mature functional macrophages. Thus, we have found that exogenous GM-CSF augments the primary plaque-forming response to sheep red blood cells and that this effect is due to upregulation of Ia antigen expression and interleukin 1 production by the macrophages. We also show that GM-CSF inhibits the replication of Trypanosoma cruzi in cultured peritoneal macrophages and causes an accelerated clearance of Salmonella typhimurium from the peritoneal cavity of mice. These data indicate that GM-CSF is a multifunctional molecule stimulating both hematopoiesis and mature macrophage function. 相似文献
100.
Harrod KS Jaramillo RJ Rosenberger CL Wang SZ Berger JA McDonald JD Reed MD 《American journal of respiratory cell and molecular biology》2003,28(4):451-463
Although epidemiologic data strongly suggest a role for inhaled environmental pollutants in modulating the susceptibility to respiratory infection in humans, the underlying cellular and molecular mechanisms have not been well studied in experimental systems. The current study assessed the impact of inhaled diesel engine emissions (DEE) on the host response in vivo to a common pediatric respiratory pathogen, respiratory syncytial virus (RSV). Using a relatively resistant mouse model of RSV infection, prior exposure to either 30 microg/m3 particulate matter (PM) or 1,000 microg/m3 PM of inhaled DEE (6 h/d for seven consecutive days) increased lung inflammation to RSV infection as compared with air-exposed RSV-infected C57Bl/6 mice. Inflammatory cells in bronchoalveolar lavage fluid were increased in a dose-dependent manner with regard to the level of DEE exposure, concomitant with increased levels of inflammatory mediators. Lung histology analysis indicated pronounced peribronchial and peribronchiolar inflammation concordant with the level of DEE exposure during infection. Mucous cell metaplasia was markedly increased in the airway epithelium of DEE-exposed mice following RSV infection. Interestingly, both airway and alveolar host defense and immunomodulatory proteins were attenuated during RSV infection by prior DEE exposure. DEE-induced changes in inflammatory and lung epithelial responses to infection were associated with increased RSV gene expression in the lungs following DEE exposure. These findings are consistent with the concept that DEE exposure modulates the lung host defense to respiratory viral infections and may alter the susceptibility to respiratory infections leading to increased lung disease. 相似文献