Activation of the Ki-ras protooncogene in spontaneously occurring and chemically induced lung tumors of the strain A mouse.

The strain A mouse has a high incidence of spontaneous lung tumors and is susceptible to lung tumor induction by chemical carcinogens. By utilizing transfection assay, Southern blot analysis, and DNA amplification techniques, we have detected an activated Ki-ras gene in the DNAs of both spontaneously occurring and chemically induced lung tumors of strain A mice. The point mutations in the spontaneous lung tumors were in both codon 12 (60%) and codon 61 (30%). In contrast, 100% of the mutations in the Ki-ras gene detected in methylnitrosourea-induced lung tumors and 93% of the mutations in the Ki-ras genes detected in benzo[a]pyrene-induced lung tumors were in codon 12, whereas 90% of the mutations in the Ki-ras genes detected in ethyl carbamate-induced lung tumors were in codon 61. The selectivity of mutations in the Ki-ras oncogene observed in chemically induced tumors, as compared to spontaneous tumors, suggests that these chemicals directly induce point mutations in the Ki-ras protooncogene. These data indicate that the strain A mouse lung tumor model is a very sensitive system to detect the ability of chemicals to activate the Ki-ras protooncogene in lung tissue.     

Inhibitory effects of phenethyl isothiocyanate on N-nitrosobenzylmethylamine carcinogenesis in the rat esophagus

F-344 rats fed diets containing phenethyl isothiocyanate (PEITC; 3 and 6 mumol/g diet), a naturally occurring constituent of cruciferous vegetables, before and during treatment with the carcinogen N-nitrosobenzylmethylamine (NBMA), developed 99-100% fewer esophageal tumors than NBMA-treated control rats. PEITC exhibited inhibitory effects against both preneoplastic lesions (acanthosis and hyperkeratosis, leukoplakia, leukokeratosis) and neoplastic lesions (papilloma, carcinoma). Tumors were not observed in rats treated with PEITC alone. The effects of PEITC (10, 25, 50, 100 microM) on the metabolism and DNA binding of NBMA in cultured explants of rat esophagus were also investigated. PEITC produced a marked (53-97%) dose-dependent inhibition in the binding of NBMA metabolites to DNA and in the levels of DNA methylation at the N7 (20-89%) and O6 (55-93%) positions of guanine. This isothiocyanate also reduced the metabolism of NBMA by esophageal tissues as indicated by increased amounts of unmetabolized NBMA in the medium of cultures containing PEITC. Collectively, these data indicate that PEITC is a potent inhibitor of NBMA-induced esophageal carcinogenesis in rats.     

Safety and efficacy of intravascular ultrasound-guided inferior vena cava filter in super obese bariatric patients.

BACKGROUND: The morbidly obese (body mass index >40 kg/m(2)) are at significant risk of postoperative venous thromboembolism (VTE). Pulmonary embolism is the leading cause of death after Roux-en-Y gastric bypass, approximating .5%. Because of the technical limitations with fluoroscopy and table weight limits, it has been our practice at our university-based bariatric center to offer intravascular ultrasound (IVUS)-guided inferior vena cava filter (IVCF) placement at Roux-en-Y gastric bypass to patients with a history of VTE, hypercoagulable state, or profound immobility. METHODS: The hospital and outpatient records of all 594 patients who underwent Roux-en-Y gastric bypass from January 1, 2004 to October 31, 2006 were reviewed. The patients who had undergone concurrent IVUS-guided IVCF placement were selected. The co-morbidities, outcomes, and complications were recorded. RESULTS: Of the 594 patients, 31 (mean body mass index 71.2 +/- 2.96 kg/m(2)) had undergone concurrent IVUS-guided IVCF placement. The indications included a history of VTE (n = 5), a known hypercoagulable state (n = 2), and profound immobility (n = 25). The technical success rate was 96.8%. One filter was malpositioned in the iliac vein. No catheter site complications occurred. A ventilation/perfusion scan and computed tomography scan each detected pulmonary embolism in 2 surviving patients within 2 months postoperatively. Two patients died, 1 on postoperative day 8 and 1 on postoperative day 15 (6.4%). The mean follow-up time was 262.8 +/- 37.3 days. Autopsy excluded VTE or IVCF-related issues as the cause of death in both patients. CONCLUSION: These results suggest the efficacy of IVUS-guided IVCF placement in preventing mortality from pulmonary embolism in high-risk bariatric patients. IVUS-guided IVCF placement can be safely performed with an excellent success rate in high-risk patients who would not otherwise be candidates for intervention because of the technical limitations of fluoroscopy.     

Implications of progressive multifocal leukoencephalopathy and JC virus for the etiology of MS

JCV infects oligodendrocytes and, to a lesser extent, astrocytes in the brain and spinal cord and causes the demyelinating disease known as progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals. The possibility exists that this opportunistic infection reactivates from a latent state in the brain. It is proposed that the pathogenetic immune response in a multiple sclerosis (MS) brain may be directed predominantly toward antigens of a DNA virus, such as JCV, which is latent in glial cells. The target antigens could be synthesized only during transient viral reactivation or could persist, thus explaining the two basic patterns of neurological symptoms in MS. It is further proposed that the viral genome as a minichromosome becomes focally distributed in glial cells following vertical passage in dividing progenitor cells after infection early in life. The concept that the host response to a single agent can evoke two distinct pathologies (PML and MS) derives from a chronic mycobacterial infection of peripheral nerves-leprosy.     

医用聚乳酸类高分子材料的应用

目的:阐述医用聚乳酸类高分子材料的需求,综述聚乳酸类高分子材料在生物医学领域的应用,并对其在医学领域的应用前景进行展望。资料来源:应用计算机检索ACS美国化学学会数据库2000-01/2006-12关于医用聚乳酸类高分子材料的文章,检索词“polylactide”;利用Elsevier Science全文电子期刊数据库2000-01/2006-12进行检索,检索词“polylactide”和全文检索“Medical polymeric material”。同时利用计算机检索中国期刊全文数据库1994-01/2005-12的相关文章,限定文章语言种类为中文,检索词“聚乳酸类医用高分子材料”。资料选择:对资料进行初审,纳入标准:①关于聚乳酸类医用高分子材料的需求。②医用聚乳酸类高分子材料的合成及应用。排除标准:重复性研究。资料提炼:共收集到符合上述要求的文献100篇,排除70篇重复性研究。30篇符合纳入标准:其中6篇关于聚乳酸类医用高分子材料的需求,24篇关于医用聚乳酸类高分子材料的合成及应用。资料综合:聚乳酸是一种具有良好的生物相容性和可生物降解的聚合物,最终的降解产物是二氧化碳和水,对人体无毒、无刺激。目前,聚乳酸类材料产品在医学领域广泛用于药物控制释放载体、组织工程、骨内固定、修复、手术缝合线、人造皮肤以及三维多孔支架等。结论:医用聚乳酸类高分子材料有非常广阔的应用前景,今后研究的重点是研发高效低成本的聚乳酸制备方法,合成适应于不同医疗或其他用途的、具有优良生物相容性的聚乳酸共聚物高分子材料。     

Kinetics of peripheral blood mononuclear cell mobilization with chemotherapy and/or granulocyte-colony-stimulating factor: implications for yield of hematopoietic progenitor cell collections

BACKGROUND: Peripheral blood progenitor cells (PBPCs) are commonly collected and used to reconstitute hematopoiesis after high-dose chemotherapy. However, strategies for optimal collection and assessment of leukapheresis components are not standardized. STUDY DESIGN and METHODS: Hematopoietic progenitor cell assays were performed on 369 leukapheresis components collected from 95 patients who had received doxorubicin-based chemotherapy and/or granulocyte-colony-stimulating factor (G-CSF). Precollection patient hematologic values, leukapheresis collection values, component hematopoietic progenitor cell assays, and patient outcome measures were summarized. The kinetics of mononuclear cell (MNC) and PBPC mobilization were assessed among four patient groups. RESULTS: Patient group was a significant predictor of the peripheral blood MNC count on the day of collection (p<0.0001), and that value was a significant predictor of granulocyte-macrophage– colony-forming unit (CFU-GM) yield (p<0.0001). This relationship between the peripheral blood MNC count on the day of collection and CFU- GM yield differed according to patient group (p<0.0001). CFU-GM made up a larger fraction of peripheral blood MNCs collected from patients who received chemotherapy plus G-CSF than collected from those who received G-CSF alone. Moreover, the peripheral blood MNC count and the corresponding CFU-GM yield increased significantly on consecutive days of collection in patient groups receiving chemotherapy and G-CSF but were unchanged or decreased in patients receiving G-CSF alone. CONCLUSION: The relationship between peripheral blood MNC count and leukapheresis component CFU-GM yield differed significantly between patients who received chemotherapy and G-CSF and those who received G- CSF alone for the mobilization of PBPCs. Patient peripheral blood MNC count and component CFU-GM yield are useful for both assessing and suggesting revisions to PBPC mobilization and collection strategies.     

Black patients present with more severe vascular disease and a greater burden of risk factors than white patients at time of major vascular intervention

Background

Although many studies have demonstrated racial disparities after major vascular surgery, few have identified the reasons for these disparities, and those that did often lacked clinical granularity. Therefore, our aim was to evaluate differences in initial vascular intervention between black and white patients.