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Biomedical subjects

J B Faust

Publications and source records attributed to J B Faust.

13 recordsLinked to original sources

Amplification and expression of the bcl-1 gene in human solid tumor cell lines.

The bcl-1 gene maps to chromosome 11q13 and has recently been shown to be a member of the cyclin gene family. Amplification of the chromosome region containing bcl-1 occurs frequently in breast cancer, squamous cell cancer, and other tumor types. We have hypothesized that amplification results in altered expression of the bcl-1 gene, contributing to carcinogenesis. In this work, we studied bcl-1 gene amplification and expression in a panel of human cell line. bcl-1 is expressed in all cell lines studied. The level of expression tends to be higher in amplified cell lines. We also screened these cell lines for int-2 and hst-1 expression, genes which are frequently coamplified with bcl-1. No int-2 expression was detected, and the two cell lines expressing hst-1 were unamplified. Our data provide support for the importance of bcl-1 in carcinogenesis.

Blotting, Northern↗

Characterization of liver epithelial cells transfected with myc and/or ras oncogenes.

While many liver tumors contain activated myc and ras oncogenes, the mechanisms by which these genes contribute to cellular transformation is poorly understood. Activated versions of the cellular oncogenes, c-myc and/or c-H-ras were transfected into normal rat liver epithelial cells to identify cellular pathways that are altered in the cells containing the oncogenes. The results of these and other investigations indicate that the biological properties associated with the transfection of c-myc include immortalization, reduced contact inhibition of growth, activation of phospholipase A2-mediated pathways, increased sensitivity to transformation with a ras gene, and greatly increased sensitivity to growth factors. The biological properties associated with the transfection of the ras gene include morphological transformation, anchorage-independent growth, tumorigenicity, increased phosphatidylinositol metabolism, the induction of growth-factor processing and secretion, which leads to (exogenous) growth factor-independent tumor growth, and a marked resistance to normal inhibitors of growth such as TGF-beta. It is proposed that the complementary actions of the myc and ras genes in cellular transformation may be related to the ras-induced secretion of autocrine growth factors by cells sensitized to their effects by the myc gene. The increased stimulus for growth coupled to a ras-induced insensitivity to growth inhibitors may lead to clonal expansion of these cells and tumor development.

Animals↗

Strontium toxicity in Drosophila melanogaster.

The Drosophila strains v;bw and Austin represent the extremes in resistance and sensitivity, respectively, to the toxic effects of CdCl2 in the diet. Using the six genotypes containing the possible combinations of the three main chromosomes for v;bw and Austin, we had shown previously that the gene(s) for cadmium resistance is on the X-chromosome. In this paper it is shown, using the same six genotypes, that the gene(s) for strontium resistance is on the second chromosome, as measured by LC50 values.

Animals↗

Characterization of a candidate bcl-1 gene.

The t(11;14)(q13;q32) translocation has been associated with human B-lymphocytic malignancy. Several examples of this translocation have been cloned, documenting that this abnormality joins the immunoglobulin heavy-chain gene to the bcl-1 locus on chromosome 11. However, the identification of the bcl-1 gene, a putative dominant oncogene, has been elusive. In this work, we have isolated genomic clones covering 120 kb of the bcl-1 locus. Probes from the region of an HpaII-tiny-fragment island identified a candidate bcl-1 gene. cDNAs representing the bcl-1 mRNA were cloned from three cell lines, two with the translocation. The deduced amino acid sequence from these clones showed bcl-1 to be a member of the cyclin gene family. In addition, our analysis of expression of bcl-1 in an extensive panel of human cell lines showed it to be widely expressed except in lymphoid or myeloid lineages. This observation may provide a molecular basis for distinct modes of cell cycle control in different mammalian tissues. Activation of the bcl-1 gene may be oncogenic by directly altering progression through the cell cycle.

Amino Acid Sequence↗

Ecological toxicology and human health effects of heptachlor.

The chlorinated cyclodiene heptachlor was registered in 1952 as an agricultural and domestic insecticide. By early 1984, registration for all purposes, except subterranean termite control and for limited use in the control of fire ants, had been cancelled. This restriction of use arose primarily from concerns over the environmental persistance and bioaccumulation potential of the organochlorine pesticides. Currently, sale of heptachlor has been voluntarily suspended over questions about its carcinogenic potential, and the absence of safe and effective application methods. As a persistent organochlorine pesticide, heptachlor residues are detected in all components of the environment. In historical use, heptachlor was directly applied to terrestrial systems, while air and water were secondarily contaminated via volatilization and land run-off, respectively. Within each environmental compartment, heptachlor undergoes a variety of metabolic and abiotic transformations. In vivo studies indicate that heptachlor epoxide is the predominant metabolite, formed as a product of the mixed-function oxidase system, while 1-hydroxychlordene is the major soil metabolite. For quantification, heptachlor and its metabolites are extracted from air, soil and sediment, water, or biological materials using various organic solvents and analyzed by gas chromatography or thin-layer chromatography. Residue reports comprise most of the literature concerning the effects of heptachlor on the biota. In many such reports, toxic effects cannot be conclusively attributed to heptachlor exposure. Toxicity to organisms seems more dependent on acute exposure, while the chronic effects of low level exposure to heptachlor are poorly defined. Maximal terrestrial residues coincide with temporal and spatial proximity to application; peak residues in aquatic systems on the other hand, correlate to periods of maximum run-off. The lipophilic nature of both heptachlor and heptachlor epoxide results in the potential for significant bioaccumulation in all lipid-type compartments in the environment. The toxic effects of heptachlor are not specific for any one organ system. The liver and the central nervous system are most significantly affected by heptachlor, although effects can also be seen in the reproductive, hematopoietic, immune, and renal systems. An important consideration is the relation of relevant environmental exposure levels to toxicity. The concentrations necessary to elicit results in laboratory experiments do not translate directly to the same results upon environmental exposure, nor do experimental laboratory animal models absolutely equate with native-state organisms or with humans.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Oncogene activation and hepatocarcinogenesis.

Dominant-transforming oncogenes are frequently detected in mouse liver tumors, but are rare or inconsistently detected in rat liver tumors. Most of those that have been identified are members of the ras family. While altered expression of many oncogenes has been reported, an increase in the expression of the c-myc gene is consistently observed in both rat and mouse hepatocellular tumors. Both hepatocytes and liver epithelial cells have been immortalized or transformed with viral or cellular oncogenes. Immortalization of cells occurs without the loss of differentiated functions, while transformation induces the expression of many genes/gene products associated with liver cancer in vivo. Cells transformed with chemical carcinogens or oncogenes display a phenotype of growth factor independence or greatly reduced growth factor requirements. Transformation is frequently associated with a substantial decrease in the expression of the exogenous growth factor receptor in the hepatocellular tumors.

Animals↗

Cadmium resistance in Drosophila: a small cadmium binding substance.

A small cadmium-binding substance (CdBS) has been observed in adult Drosophila melanogaster that were raised for their entire growth cycle on a diet that contained 0.15 mM CdCl2. Induction of CdBS was observed in strains that differed widely in their sensitivity to CdCl2. This report describes the induction of CdBS and some of its characteristics.

Animals↗

The consumer health information library in the hospital setting.

Consumer health information has become an accepted and fast-growing facet of the consumer movement. The questions now center on the feasibility of providing such information and the best way of offering this service in the hospital setting. This paper examines one hospital-based lay health library and discusses staffing, services, administration, physical facilities, accessibility, and librarian liability.

Consumer Advocacy↗

Microcomputers as on-line catalogs in special libraries.

This article discusses the rationale for the conversion of a card catalog to an on-line system in a special library owning approximately 4000 titles. Equipment, software, and procedures are described. Pros and cons of the use of a microcomputer for such a project, as well as costs and personnel needs, are outlined.

Catalogs, Library↗