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Transgenic mice overexpressing the pim-1 oncogene in their lymphoid compartments are predisposed to T-cell lymphomagenesis but only to the extent that approximately 10% of the transgenic mice develop lymphomas within 34 weeks after birth. Recently, we have shown that lymphomagenesis in pim-1 transgenic mice can be accelerated by infecting pim-1 transgenic mice with murine leukemia viruses or by treating the mice with a relatively low dose of 60 mg of the carcinogen N-ethyl-N-nitrosourea (ENU) per kg of body weight. Here we describe the incidence of tumors as a function of the dose of ENU. Either 200, 15, 4, 1, or 0.1 mg/kg ENU was injected into transgenic and control mice and the tumor incidence was monitored. T-cell lymphomas developed in 100 and 70% of the pim-1 transgenic mice treated with 200 and 15 mg/kg ENU, respectively. Approximately 20% of the Emu-pim-1 transgenic mice developed lymphomas after treatment with either 4, 1, or 0.1 mg/kg ENU. The nontransgenic mice developed lymphomas only after injection with 200 mg/kg (45%). The data show that Emu-pim-1 transgenic mice are approximately 25-fold more susceptible to ENU-induced lymphomagenesis than control mice. In most tumors the expression of c-myc was strongly elevated, probably as a direct or indirect effect of ENU. Analysis of the lymphomas for ras mutations revealed that approximately 10% of the lymphomas bear a ras mutation. The data indicate that at least some of these mutations are not the direct result of alkylation by ENU but rather represent spontaneous mutations that occurred later in the tumorigenic process.
The liver/islet (GLUT2) and muscle/adipose tissue (GLUT4) glucose-transporter gene products, membrane proteins that facilitate glucose uptake into cells, are important molecules for normal carbohydrate metabolism. Recent isolation of the genes encoding these proteins provides a means to assess the role of possible defects that might contribute to impaired glucose-stimulated insulin secretion or impaired insulin-mediated glucose uptake, both prominent phenotypic features of non-insulin-dependent diabetes (NIDDM). A GLUT2 cDNA clone was isolated from a human liver cDNA library to search for polymorphisms at this locus in American Blacks. Three highly polymorphic sites were identified, one of which (EcoRI-Hae III) appears to be due to an insertion and/or deletion of 200 base pairs of DNA. Significant linkage disequilibrium between these sites over approximately 30 kilobases of genomic DNA suggested that these polymorphisms could be in linkage disequilibrium with mutations at this locus if they exist. A GLUT4 cDNA clone was also utilized to search for polymorphisms at this locus, but only one previously described polymorphism was observed. GLUT2 and GLUT4 cDNA probes were used to evaluate DNA polymorphisms in genomic DNA from American Blacks with NIDDM. The allelic, genotypic, and haplotypic frequencies of the DNA polymorphisms at these loci did not differ from the frequencies in nondiabetic subjects. Because no associations with NIDDM were found, it appears unlikely that mutations at these loci contribute in a major way to the genetic susceptibility to NIDDM observed in American Blacks.
The expression of members of the family of matrix-degrading metalloproteinases (MMPs) is believed to contribute to the complex process of invasion and metastasis. In this study, specific cDNA probes for three members of the stromelysin subfamily of MMPs--stromelysin (MMP-3), stromelysin-2 (MMP-10), and pump-1 (MMP-7)--were used to examine the expression of these three different MMPs in human gastric and colonic carcinomas and in adjacent normal mucosa. The expression of pump-1 mRNA in malignant colon and stomach samples was striking. In a total of 10 gastric carcinoma samples examined, eight (80%) expressed pump-1 transcripts; similarly, 6 of 8 (75%) colon carcinoma samples were also positive. Stromelysin and stromelysin-2 mRNAs were not detected in any of these samples. Expression of the MMPs examined was not detected in any of the adjacent, grossly normal tissue samples. Using in situ hybridization and affinity purified anti-pump-1 antibodies, the expression of pump-1 mRNA and protein was localized to tumor cells and was not detected in stromal or lymphocytic cells. This data suggests that the inappropriate expression of pump-1 by malignant cells may contribute to the neoplastic phenotype.
To date, three closely-related TGF beta genes have been found in the mouse; TGF beta 1, TGF beta 2 and TGF beta 3. Previous experiments have indicated that TGF beta 1 and TGF beta 2 may play important roles during mouse embryogenesis. The present study now reports the distribution of transcripts of TGF beta 3 in comparison to the other two genes and reveals overlapping but distinct patterns of RNA expression. TGF beta 3 RNA is expressed in a diverse array of tissues including perichondrium, bone, intervertebral discs, mesenteries, pleura, heart, lung, palate, and amnion, as well as in central nervous system (CNS) structures such as the meninges, choroid plexus and the olfactory bulbs. Furthermore, in several organ systems, TGF beta 3 transcripts are expressed during periods of active morphogenesis suggesting that the protein may be an important factor for the growth and differentiation of many embryonic tissues.
We have developed a method for using short (30-42 base pair) synthetic oligonucleotide DNA probes in Northern blot assays. The method involves labeling the probes to high specific activity, very stringent hybridization and wash conditions, and the presence of several inhibitors of nonspecific binding in the hybridization buffer. We have tested this method with several probes obtained from local and commercial sources. The results with every probe used were high signal-to-noise ratios in an exposure time range of 30 min to 7 days.
A cross-sectional study was undertaken to determine the prevalence of Mycoplasma fermentans infection in patients with human immunodeficiency virus (HIV) infection using polymerase chain reaction methodology. Targeted M. fermentans DNA sequences could be amplified from the DNA extracted from the blood of 6 (11%) of 55 HIV-seropositive patients but from none of 26 HIV-seronegative subjects at low risk for HIV infection (P = .17). There was no correlation between M. fermentans infection and HIV clinical stage. There was a nonsignificant trend toward an association between M. fermentans infection and a history of syphilis. Infection with M. fermentans may occur more commonly in HIV-infected patients; however, a role as a copathogen or opportunistic infection was not established in this study.
A novel protein tyrosine kinase (PTK) substrate, p120, has been previously implicated in ligand-induced signaling through the epidermal growth factor, platelet-derived growth factor and colony-stimulating factor 1 receptors, and in cell transformation by p60v-src. We have isolated a near full-length cDNA encoding murine p120. The encoded protein lacks significant homology with any reported protein, but it contains four copies of an imperfect 42 amino acid repeat that occurs 12.5 times in the protein encoded by Drosophila armadillo (arm), and its direct homologs, human plakoglobin (plak) and Xenopus laevis beta-catenin (beta-cat). The presence of this motif implies that p120 may share at least one aspect of its function with the arm protein and its homologs.