Loss of heterozygosity and mutational analysis of the PTEN/MMAC1 gene in synchronous endometrial and ovarian carcinomas

Mutations of the human putative protein tyrosine phosphatase (PTEN/MMAC1) gene at chromosome 10q23 have been found frequently in type I endometrial carcinomas. Endometrioid adenocarcinoma is the most frequent histology seen in patients with clinically determined synchronous endometrial and ovarian carcinomas. We report a high incidence of PTEN/MMAC1 mutations and 10q23 loss of heterozygosity (LOH) in patients with synchronous endometrial and ovarian carcinomas. Paraffin-embedded precision microdissected tumors were analyzed for 10 matched synchronous endometrial and ovarian cancers and 11 matched control metastatic endometrial cancers. Single-stranded conformation polymorphism analysis was used to screen for mutations in all tumors and corresponding normal lymphocyte DNA. LOH was determined using a panel of four microsatellite markers within the PTEN/MMAC1 locus. PTEN/MMAC1 mutations were found in 43% (9 of 21) of the endometrial cancers studied, similarly represented in the clinically synchronous group (5 of 10 or 50%) and the advanced metastatic group (4 of 11; 36%; P = 0.53). In two of the five cases of clinically synchronous cancers, identical or progressive PTEN mutations were found in both the endometrial and ovarian cancers, suggesting that the ovarian tumor is a metastasis from the endometrial primary. PTEN/MMAC1 mutations in the advanced endometrial cancers were similar in the corresponding metastases. In one case, the mutation was seen in only one of two metastatic lymph nodes. The LOH analysis demonstrated 55% LOH in at least one PTEN/MMAC1 marker. These findings suggest that the putative tumor suppressor gene PTEN/MMAC1 may be a viable molecular marker to differentiate synchronous versus metastatic disease in a subset of clinically synchronous endometrial and ovarian carcinomas.     

迎接大数据和数据专家

导读 全球领先的信息技术研究和咨询公司Gartner近日在北京举行主题为“大数据时代及分析”的本地研讨会。来自Gartner的顶尖分析师们与大家共同聚焦信息管理，分析新型创新模式，探索如何提高绩效管理并创造新的收益，帮助客户向着商业目标不断前进。     

Serum digoxin in the presence of digibind: determination of digoxin by the Abbott AxSYM and Baxter Stratus II immunoassays by direct analysis without pretreatment of serum samples

We have reevaluated the feasibility of using direct immunochemical methods to track free digoxin in patients receiving Digibind. We report here that results obtained by the Stratus II and AxSYM immunoassays on patients receiving digoxin (without Digibind), digoxin-fortified serum samples supplemented with Digibind, and a digitoxic patient treated with Digibind, show no clinically significant biases. We conclude that useful free digoxin concentrations may be obtained for Digibind-treated patients using either the AxSYM or Stratus immunoassays without subjecting samples to ultrafiltration before analysis.     

Abnormal duodenal bile composition in patients with acalculous chronic cholecystitis

The purpose of this study was to evaluate the effects of the calcification inhibitors FeCl3 and sodium dodecyl sulfate (SDS) on the morphology of glutaraldehyde-crosslinked type I collagen sponges and on their serum conditioning. Scanning electron microscopy (SEM) showed that the morphology of the sponges, already modified by glutaraldehyde crosslinking, underwent further changes after treatment of the hydrogels with inhibitors. Coral-like structures were found to branch from the bulk of the material especially in the case of SDS-treated samples. The composition and morphology of the conditioning layers was characterized after 48 h incubation in serum by SDS-polyacrylamide gel electrophoresis-immunoblot of the adsorbed proteins, by energy-dispersive X-ray analysis of the elements (EDX), and by SEM of the conditioned surfaces. All the samples showed the adsorption of proteins with molecular weights ranging from 10 to 203 kD. However, the peculiar adsorption of an approximately 10-kD band (complement C3 fragment) and of fibronectin were detected in the case of glutaraldehyde-crosslinked collagen. On the other hand, glutaraldehyde-crosslinked collagen treated with 0.1M FeCl3 showed the remarkable adsorption of a 29-kD band. The glutaraldehyde-crosslinked hydrogels showed the massive precipitation of crystals on their exposed surfaces, whereas a disordered network structure surrounding the collagen fibrils was found in the case of the samples pretreated with inhibitors. A predominant precipitation of sodium and chloride was detected in all the sponges, although the ratio between the peaks changed from from one hydrogel to another. The results reported in this article clearly indicate that the treatments with SDS and FeCl3 change the surface conditioning of collagen sponges, suggesting a possible role of deposited serum solutes in affecting mineralization processes on bioprosthesis.     

Genetic requirements for local and systemic movement of tomato golden mosaic virus in infected plants

Tomato golden mosaic geminivirus (TGMV) has two DNA components, A and B. Replication of DNA A can be detected in inoculated leaves, but DNA B is additionally required for virus movement in planta. Using viral DNA accumulation as an indication of the number of infected cells, we show here that both the BL1 and BR1 genes are necessary for local TGMV movement. We also demonstrate that transient expression of BL1 and BR1 together allows wild-type TGMV DNA A to move systemically. When the transient movement assay was used to analyze various A component mutants, all were found to move locally in inoculated leaves, and only an ar1 (coat protein) mutant was unable to move systemically. In addition, we confirm that a TGMV al2 (AR1 and BR1 trans-activator) mutant has a defect in local movement which can be rescued by provision of exogenous BR1, but not BL1. Finally, we show that the ability of TGMV coat protein mutants to accumulate single-stranded (ss) DNA is dependent on BR1. These results provide experimental evidence obtained in planta which supports three predictions of published models for bipartite geminivirus movement: (i) BL1 and BR1 have distinct and essential roles in cell-to-cell movement as well as systemic movement; (ii) BR1 may interact with viral ssDNA in vivo; and (iii) AL2 is indirectly required for movement through its effect on BR1 expression. In addition, our data suggest that specific models of bipartite geminivirus systemic movement should accommodate a role for the coat protein.     

Use of hepatitis A vaccine in a community-wide outbreak of hepatitis A

Hepatitis A outbreaks in communities are often difficult to control. From July 1994 through June 1995, 676 cases of hepatitis A were reported in Shelby County, Tennessee. With the licensure of a hepatitis A vaccine in February 1995, a new tool for outbreak control became available. During August-October 1995, a mass vaccination campaign was conducted. A total of 34,054 children received the first dose of hepatitis A vaccine. From December 1995 through December 1996, the number of hepatitis A cases reported inside the intervention area declined by 64%; outside the intervention area, the number of cases declined by 40%. The precise contribution of the vaccine campaign to the decline in the number of outbreak cases is difficult to quantify because community outbreaks often wane over time. The vaccine campaign may have hastened the decline of the number of outbreak cases. Future interventions should consider an earlier campaign with greater vaccine coverage.