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Biomedical subjects

S A Becker

Publications and source records attributed to S A Becker.

At least 19 recordsLinked to original sources
PubMed2000

Dissociation of DDB1-binding and transactivation properties of the hepatitis B virus X protein.

The hepatitis B virus (HBV) X protein (HBx) is a transactivator encoded by mammalian hepadnaviruses, and is thought to stimulate transcription by interacting with one or more host cell factors. Numerous cellular proteins have been reported to interact with HBx including a component of the nucleotide excision repair complex called ultraviolet damaged DNA binding (UV-DDB, or DDB1) protein. Recent studies have identified a role for DDB1 in transcription, raising the possibility that HBx may acquire its broad transcriptional properties by interacting with DDB1. A panel of HBx mutant proteins, some of which no longer bind to DDB1, was used to test this hypothesis. Plasmid DNAs encoding HBx wildtype and mutant derivatives were transfected into HepG2 cells, and their ability to transactivate a cotransfected reporter plasmid tested. Results from the transactivation assays in HepG2 cells were then compared with data obtained from HBx-DDB1 binding studies performed in yeast. Several HBx mutant proteins unable to bind DDB1 remained competent for transactivation, indicating that HBx binding to DDB1 is not required for HBx transactivation of the ETS1 promoter. It remains possible that a subset of HBx transactivation function targets an as yet undefined DDB1-specific pathway.

DNA-Binding Proteins↗
PubMed1998

Dietary lipids alter fatty acid composition and PGE2 production in colonic lymphocytes.

The immune system can influence the development and growth of tumors, including those of the colon. Most studies of immune function utilize immune cells from the blood. Colonic mucosa, however, contains independently functioning lymphocytes that may have significant impact on colon tumor formation. Dietary lipids are known to influence the development of colon tumors and the function of peripheral immune cells. This study was designed to determine dietary lipid effect colonic lymphocytes (CL). CL were isolated from rats fed a diet high in corn oil or menhaden oil and cultured for 72 hours in the presence of absence of mitogen stimulation. Fatty acid composition of CL was measured by gas chromatography. Prostaglandin E2 levels were measured in conditioned media by enzyme-linked immunosorbent assay. CL proliferation rates were determined by colorimetric assay and thymidine incorporation. Results showed that CL from rats fed a diet high in corn oil had greater membrane concentrations of linoleic and arachidonic acids and higher levels of prostaglandin E2 production than those from rats fed a menhaden oil diet. Mitogen stimulation did not increase CL proliferation. Antitumor effects of n-3 fatty acids in the colon may involve anti-inflammatory responses by colonic lymphocytes.

Animals↗
PubMed1998

Hepatitis B virus X protein interferes with cellular DNA repair.

The hepatitis B virus X protein (HBx) is a broadly acting transactivator implicated in the development of liver cancer. Recently, HBx has been reported to interact with several different cellular proteins, including our report of its binding to XAP-1, the human homolog of the simian repair protein UVDDB. In the present study, several HBx mutants were used to localize the minimal domain of HBx required for binding to XAP-1/UVDDB to amino acids 55 to 101. The normal function of XAP-1/UVDDB is thought to involve binding to damaged DNA, the first step in nucleotide excision repair (NER); therefore, we hypothesized that this interaction may affect the cell's capacity to correct lesions in the genome. When tested in two independent assays that measure NER (unscheduled DNA synthesis and host cell reactivation), the expression of HBx significantly inhibited the ability of cells to repair damaged DNA. Under the assay conditions, HBx was expressed at a level similar to that previously observed during natural viral infection and was able to transactivate several target reporter genes. These results are consistent with a model in which HBx acts as a cofactor in hepatocarcinogenesis by preventing the cell from efficiently repairing damaged DNA, thus leading to an accumulation of DNA mutations and, eventually, cancer. An adverse effect on cellular DNA repair processes suggests a new mechanism by which a tumor-associated virus might contribute to carcinogenesis.

Animals↗
PubMed1996

Frequent loss of chromosome 8p in hepatitis B virus-positive hepatocellular carcinomas from China.

The majority of hepatocellular carcinomas (HCCs) from hepatitis B virus (HBV)-endemic areas contain integrated viral sequences. To better understand the role of HBV DNA insertion in tumorigenesis, we examined the integration site of a HCC harboring a single insert. Cellular DNAs flanking the viral sequences were mapped to chromosomes 17 and 8, indicating a translocation had occurred at the site of viral integration. Regional mapping of chromosome 17 demonstrated that HBV had integrated in 17p12-pter, a region that harbors the p53 tumor suppressor gene. Many studies have shown that chromosome 17p allele loss occurs frequently in HCCs from certain geographical areas. To investigate the chromosome 8 allele status in Chinese HCCs, a panel of 37 matched normal and HCC DNAs from Qidong, China was analyzed for tumor-specific allele loss with RFLP probes from both arms of chromosome 8. Tumor-specific loss of heterozygosity was highest on the short arm with 71.4% (10/14) and 85.0% (17/20) of the informative patients missing an allele for 8p23 (YNM3) or 8p21 (NEFL), respectively. Allele loss from the long arm of chromosome 8 was also observed with 30.0% (6/20) and 33.3% (7/21) of the samples informative for 8q22 (CA2) and 8q24 (MCT128.2), respectively. The high allele loss on 8p correlates with recent studies of other human cancers and is interpreted to indicate that a tumor suppressor gene(s) whose loss is important for carcinogenesis lies within this region. These findings also support a model in which HBV insertions associated with gross chromosomal changes can identify genomic regions where alteration is important for development of some HCCs.

Carcinoma, Hepatocellular↗
PubMed1993

Morphological response of Bilophila wadsworthia to imipenem: correlation with properties of penicillin-binding proteins.

The penicillin-binding protein (PBP) patterns of six strains of Bilophila wadsworthia were investigated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and subsequent fluorography of membrane preparations labelled with [3H]benzylpenicillin. The PBP profiles among the strains were similar; generally, seven to nine PBP-reactive bands could be visualized; their molecular weights ranged from 31 to 137 kDa. The relative affinities of the PBPs of four strains of B. wadsworthia for imipenem were examined and correlated with the morphological responses of the cells to imipenem. Morphological changes were examined by light and electron microscopies. Light microscopy revealed that at low concentrations (less than the MIC), imipenem induced the formation of rounded and bulging cells; rarely, elongation without filamentation was observed. In the presence of imipenem at the MIC, spheroplast formation was observed. Scanning and transmission electron microscopies revealed round forms together with larger, multilobate cells in the presence of subinhibitory concentrations of imipenem, suggesting that new growth sites were initiated while cell division was inhibited. Peeling of the outer membrane was also seen. Spheroplasts were very large (up to 30 microns in diameter) and stable in aqueous solution. Inhibition of the PBPs could be seen in the presence of low imipenem concentrations.

Bacterial Proteins↗
PubMed1992

Ultrastructure and molecular characterization of Fusobacterium necrophorum biovars.

The ultrastructural features and molecular components of 18 strains of Fusobacterium necrophorum biovars A, AB and B, isolated from animal and human infections, were examined by electron microscopy, multilocus enzyme electrophoresis (MEE) and by sodium dodecyl sulfate-gradient polyacrylamide gel electrophoresis (SDS-PAGE). High resolution scanning electron microscopy revealed that the strains possessed a convoluted surface pattern. Transmission electron microscopy showed that all strains possessed a cell wall structure typical of gram-negative bacteria. Bleb formation was not uncommon. Numerous extracellular materials, resembling lipopolysaccharide (LPS) fragments, surrounded cells of both human strains and biovar B animal strains. Biovar A field strains revealed capsules as stained by ruthenium red whereas a stock culture strain showed the capsule only when immunostabilized with hyperimmune serum. Starch gel electrophoresis showed all strains to possess adenyl kinase, glutamate dehydrogenases and lactate dehydrogenase; each enzyme migrated uniformly (monomorphic) among the strains and represented an electrotype. However, SDS-PAGE indicated differences in the protein profiles between all of the strains; the most distinctly different was a human isolate (FN 606). Silver staining to detect LPS showed extensive "ladder" patterns among the majority of biovar A strains but not in the animal biovar B strains. Immunoblotting of LPS with a rabbit antiserum prepared against phenol extracted LPS from a biovar A animal isolate (LA 19) suggested marked variability in the LPS antigens among the isolates studied.

Animals↗
PubMed1991

Mycobacterium paratuberculosis antigen D: characterization and evidence that it is a bacterioferritin.

By using a combination of agarose and polyacrylamide gel electrophoresis, Mycobacterium paratuberculosis antigen D was resolved from a crude sonicated preparation of the organism and characterized as a component with a molecular mass of approximately 400,000 Da. While this component was composed mainly of protein, with unusually high proportions of glutamic acid and leucine, it was resistant to digestion with a number of proteolytic enzymes. Structural detail revealed by electron microscopy, amino acid sequence data, and the demonstration of a Soret band in its absorption spectrum indicated that antigen D was similar to an Escherichia coli bacterioferritin.

Amino Acid Sequence↗
PubMed1989

The comparative leakage behavior of reverse filling materials.

This study compares the in vitro apical seal achieved with thermoplasticized gutta-percha used with and without a sealer cement and that achieved with dental amalgam and a varnish liner following an apicoectomy and a Class I preparation of single root teeth. The teeth were immersed in methylene blue dye for 10 days, were sectioned longitudinally, and the amount of leakage was determined. No difference in leakage was found between the apical seals achieved with thermoplasticized gutta-percha used with a sealer cement and that obtained with dental amalgam with varnish. The leakage found with thermoplasticized gutta-percha used without a sealer cement was significantly greater.

Dental Amalgam↗
PubMed1989

Adenocarcinoma of the salivary gland in a white Swiss mouse.

A salivary gland adenocarcinoma in a white Swiss mouse used in a titration of the scrapie agent is reported. The neoplasm originated from the serous cells of the parotid salivary gland. Retroviral particles were detected in the neoplastic salivary gland cells by electron microscopy.

Adenocarcinoma↗
PubMed1988

Experimental peste des petits ruminants (goat plague) in goats and sheep.

In order to study the pathomorphology and immunohistochemistry of peste des petits ruminants, four goats and two sheep were inoculated intranasally with the Malig-Yemen strain of peste des petits ruminants virus. The animals developed fever, nasal discharge, oral erosions, cough and diarrhea. One goat and one sheep died and one moribund goat was killed. Three animals survived the infection. At necropsy, erosive stomatitis, pneumonia and gastroenteritis were found. Histopathologically the pneumonocytes and epithelial cells of the ileum had eosinophilic cytoplasmic and nuclear inclusions. By an indirect immunoperoxidase method, the nuclei and cytoplasm of the ileal epithelial cells of one goat contained positively (brown) stained antigen, which corresponded to viral nucleocapsids by electron microscopy. Virus appeared to be released through the microvilli of the epithelial cells. We also confirmed the formation of giant cells due to peste des petits ruminants virus.

Animals↗
PubMed1986

Gold-induced ileitis.

We describe a patient with rheumatoid arthritis who developed severe ileitis after being treated with gold salts; the patient responded to elimination of the gold therapy and to BAL.

Arthritis, Rheumatoid↗
PubMed1985

Crohn's ileitis complicated by amyloidosis: observations and therapeutic considerations.

We present a patient with clinically asymptomatic amyloidosis associated with Crohn's ileitis. A distinction should be made between immunocytic dyscrasia associated with amyloidosis (formerly primary or myeloma-associated amyloidosis) and acquired systemic amyloidosis (formerly secondary amyloidosis). We compare the natural course of amyloidosis complicating Crohn's disease with these complicating familial Mediterranean fever (FMF), and discuss the role of resection and the rationale behind colchicine therapy. Our patient is the first reported case in which colchicine therapy alone has been successful in the prophylactic treatment of amyloidosis complicating Crohn's ileitis.

Adult↗
PubMed1984

Ultrastructural comparison of Oncovirinae (type C), Spumavirinae, and Lentivirinae: three subfamilies of Retroviridae found in farm animals.

The successive steps of maturation of seven retroviruses from five species of farm animals and one retrovirus from a mouse were compared in cell cultures. The viruses included three type C oncoviruses, one spumavirus, and three lentiviruses. Although members of the 3 subfamilies shared some gross morphologic features such as budding on plasma membranes, core, and surface projections, differences were noted in the ultrastructural detail of these features. Type C oncoviruses did not show any structural differentiation in identifiable form in the cytoplasm as opposed to characteristic features observed in the spumavirus and lentivirus subfamilies, respectively. Budding viruses were distinct among the 3 subfamilies. The type C bovine leukemia virus budding on vacuole membranes differed from the two other type C viruses by lacking an electron-lucent intermediate layer as did the lentiviruses. Differentiation between type C oncoviruses and lentiviruses could be confusing because of the similarity of the fully mature virions appearing in the intercellular space. However, each subfamily of retroviruses can be readily differentiated from one another when each morphologic stage of virus replication is examined by electron microscopy.

Animals↗
PubMed1981

Myopericarditis associated with inflammatory bowel disease.

Myopericarditis is a rare but important manifestation of inflammatory bowel disease. It can be the sole or one of several extracolonic manifestations of either ulcerative colitis or Crohn's disease. Because of the therapeutic implications, we report a patient with ulcerative colitis associated with myopericarditis, with a review of the literature documenting this association.

Adult↗
PubMed1980

Influence of temperature and unstirred layers on the kinetics of glycine transport in isolated gills of Mytilus californianus.

The effect of temperature on the kinetics of glycine influx in isolated gills of Mytilus californianus was studied. Increases in temperature resulted in significant increases in the Jimax for glycine influx over the range 7--23 degrees C (Q10 = 5). Concomitant with this increase in Jimax was an increase in experimentally determined Kt, from 23 microM to 134 microM. The relationship between changes in Jimax and measured Kt was adequately described by an equation that takes into account the influence of unstirred layers on the kinetics of carrier-mediated transport. Use of this equation indicated that the changes in measured Kt could be explained by the presence of an unstirred layer approximately 400 micrometer thick over the transporting surfaces(s) of the isolated gill, and that the "true" Kt of the transport process is 1 microM. The very low values of Kt for amino acid uptake measured in intact muscles (1--3 microM) are revealed to be the product of transport processes of high affinity for substrate and a perfusion system which effectively minimizes the influence of unstirred layers, thereby permitting efficient utilization of substrate at the low concentrations characteristic of these animals' environment.

Animals↗
PubMed1979

The fine structure of mature and germinating chlamydospores of Fusarium oxysporum.

A number of features not described previously has been revealed in electron-microscope studies of mature chlamydospores of Fusarium oxysporum. On the maturation of one isolate, many spores formed a thick matrix-like layer containing electron-dense particles on the exterior surface of the spore wall. In thin sections of mature chlamydospores of the same isolate, cisternae of endoplasmic reticulum surrounding, and in close apposition to, the limiting boundary of the lipid bodies were revealed. The germination of chlamydospores was accompanied by (a) the rapid appearance of polysaccharide deposits and changes in the configuration of some subcellular organelles, (b) the formation of a new wall layer between the plasma membrane and the innermost layer of the spore wall, (c) the rupture of the outermost coats of the spore wall, and (d) the emergence of the germ tube as an extension of the new wall layer.

Cell Wall↗