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Biomedical subjects

B E Stewart

Publications and source records attributed to B E Stewart.

11 recordsLinked to original sources
PubMed1995

Differentiation-associated expression of the proto-oncogene pim-1 in cultured human keratinocytes.

The proto-oncogene pim-1 was expressed in nine human tissues (including epidermis) examined by Northern blotting. Expression of pim-1 was also observed in a number of carcinoma-derived keratinocyte lines in addition to strains derived from normal epidermis. With the exception of a squamous carcinoma line that exhibits little differentiated character in culture (SCC-4), where it was not detected, pim-1 expression was substantially higher after confluence than during log-phase growth in each case. The differentiation marker keratinocyte transglutaminase showed the same pattern of expression as pim-1 in relation to confluence in each of the cell lines and strains studied. The influences on pim-1 mRNA levels of several known effectors of keratinocyte differentiation were studied in the squamous carcinoma line SCC-9. pim-1 mRNA was stimulated by hydrocortisone and suppressed by the tumor promoter tetradecanoyl phorbol acetate. pim-1 mRNA was also regulated by calcium ion concentration in the culture medium, with expression being threefold higher in 0.15 mM than in 0.03 mM calcium ion. Keratinocyte transglutaminase was regulated similarly by these effectors. Thus pim-1 expression was associated with keratinocyte differentiation in these cultured cells.

Blotting, Northern↗
PubMed1992

Genomic structure of keratinocyte transglutaminase. Recruitment of new exon for modified function.

The gene for keratinocyte transglutaminase (TGK) spans 14 kilobase pairs and contains 15 exons. Many features of the TGK gene are very similar, if not identical, to those of the gene encoding the catalytic subunit of human clotting factor XIII: they have the same number of exons, corresponding introns always interrupt the coding region in the same phase of the codon, and most exons are of similar size (10 or 15 are exactly the same size). In these respects, the TGK and factor XIII catalytic subunit genes resemble each other more than either resembles the gene for erythrocyte band 4.2, a noncatalytic transglutaminase superfamily member. Exon II in both the TGK and factor XIII genes encodes an amino-terminal extension of nonhomologous sequence which in each protein confers a specialized function (membrane anchorage or activation of cross-linking, respectively). This suggests that the evolution of these genes included recruitment of a new exon to modify the enzyme action. Southern blots of genomic DNA reveal the presence of a TGK-like gene in birds, amphibians, and fish, but not in flies.

Amino Acid Sequence↗
PubMed1990

Primary structure of keratinocyte transglutaminase.

The nucleotide and deduced amino acid sequences of the coding regions of human and rat keratinocyte transglutaminases (protein-glutamine: amine gamma-glutamyltransferase; EC 2.3.2.13) have been determined. These yield proteins of approximately 90 kDa that are 92% identical, indicative of the conservation of important structural features. Alignments of amino acid sequences show substantial similarity among the keratinocyte transglutaminase, human clotting factor XIII catalytic subunit, guinea pig liver tissue transglutaminase, and the human erythrocyte band-4.2 protein. The keratinocyte enzyme is most similar to factor XIII, whereas the band-4.2 protein is most similar to the tissue transglutaminase. A salient feature of the keratinocyte transglutaminase is its 105-residue extension beyond the N terminus of the tissue transglutaminase. This extension and the unrelated activation peptide of factor XIII (a 37-residue extension) appear to be added for specialized functions after divergence of the tissue transglutaminase from their common lineage.

Amino Acid Sequence↗
PubMed1989

Prognosticating speech performance in multichannel cochlear implant patients.

Twenty patients received multichannel cochlear implants between April 1984 and May 1986 at the University of Utah Medical Center. All patients have been followed for at least 1 year postimplant. Preimplant screening included audiometric testing, electronystagmogram (ENG), promontory stimulation, computed tomography (CT) scanning, and psychological evaluation. Based on postimplant audio-only CID sentence discrimination scores, these patients were divided into three groups: good (CID greater than 79%), intermediate (CID, 21% to 79%), and poor (CID less than 21%). Preimplant factors that correlated with CID scores were hearing loss duration, previous use of hearing aids, lip-reading ability, tinnitus, positive ENG calorics, preimplant pure-tone average, promontory stimulation threshold, and understanding of the project. Only previous hearing aid usage approached statistical significance (p = 0.05). A larger patient sample is needed to verify these results.

Adult↗
PubMed1988

Activity of 1,1,1- and 1,1,3-trichloroacetones in a chromosomal aberration assay in CHO cells and the micronucleus and spermhead abnormality assays in mice.

1,1,1- and 1,1,3-trichloroacetones (TCA) result from the disinfection of municipal water supplies with chlorine, and are direct-acting mutagens in the Ames/Salmonella assay. The objective of this study was to further investigate the genotoxicity of these compounds in mammalian cells using an in vitro chromosomal aberration assay in Chinese hamster ovary (CHO) cells and the micronucleus and spermhead abnormality assays in mice. Both compounds induced significant increases in structural chromosomal aberrations in CHO cells in the presence and in the absence of rat S9 metabolic activation (MA). 1,1,3-TCA was more cytotoxic to CHO cells but 1,1,1-TCA resulted in a higher proportion of cells with aberrations. The clastogenic activities of both compounds were reduced in assays conducted with MA. Neither compound resulted in the induction of a significant increase in micronucleated polychromatic erythrocytes from bone marrow of Swiss-Webster mice when administered by oral gavage; nor were effects seen on the incidence of sperm with head-shape abnormalities, testis weight, or epididymal sperm concentration in B6C3F1 mice 21 or 35 days after treatment. These data indicate that the drinking water contaminants 1,1,1- and 1,1,3-TCA are clastogenic in vitro, but are not clastogenic to bone marrow cells in vivo, and do not adversely affect several indicators of testicular function in mice.

Acetone↗
PubMed1988

Multichannel cochlear implantation: Utah-design.

The Utah-design multichannel cochlear implant consists of six intracochlear monopolar electrodes, one promontory electrode, and an indifferent electrode. Connection of the intracochlear system to the external sound processor is via a percutaneous pedestal system. Four of the intracochlear electrodes receive simultaneous stimulation. Twenty patients implanted at the University of Utah with more than 1 year of sound processor use were evaluated for the study. All patients wear their sound processors on a daily basis. Seven of the 20 are able to use the telephone without special devices. Nineteen patients were tested with open set CID sentences with an average 42.2% response. A comparison was made between live voice and taped voice open-set spondee word list performance, showing slightly better overall performance with live voice.

Adult↗
PubMed1986

Chromosome analysis of trifluorothymidine-resistant L5178Y mouse lymphoma cell colonies.

Cells from small (sigma) and large (lambda) trifluorothymidine-resistant (TFTr) colonies induced by chemical mutagen treatment of TK+/-L5178Y mouse lymphoma cells were examined for chromosomal abnormalities. Analysis of G-banded metaphase chromosomes from 34 sigma-TFTr colonies revealed that cells from 20 (59%) possessed one or more chromosomal abnormalities. The most frequent (16/20 colonies) abnormality observed in cells from sigma-TFTr colonies involved the addition of extra chromatin to the distal region of one chromosome number 11. In 13 of these 16 colonies, the origin of the chromatin translocated to chromosome number 11 could not be identified; the chromatin was not missing elsewhere in the genome. The remaining three sigma-TFTr colonies with an abnormal chromosome number 11 had apparently whole chromosomes translocated, in tandem, to the distal region of chromosome number 11. Chromosomal abnormalities observed in cells from sigma-TFTr colonies with normal number 11 chromosomes included 2N/4N and 2N/4N/8N mosaicism (two colonies), a Robertsonian translocation involving chromosome 10 and a marker chromosome (one colony), and trisomy 7 (one colony). In most (14/16) sigma-TFTr colonies with structural damage to chromosome number 11, the cells within a colony were heterogeneous in that some possessed chromosomal damage whereas others were apparently normal. Analysis of chromosomes in cells from eight lambda-TFTr colonies revealed one colony in which all cells had a Robertsonian translocation involving chromosomes 1 and 16 plus other structural abnormalities. The chromosomes of cells from the remaining lambda-TFTr colonies were apparently normal.

Animals↗
PubMed1986

Stable dicentric chromosomes induced by chemical mutagens in L5178Y mouse lymphoma cells.

Stable, tandem dicentric chromosomes were discovered in two mutant cell colonies resulting from exposure of L5178Y mouse lymphoma cells to chemical mutagens. These unusual dicentrics were present in all metaphase cells examined from these colonies, even after approximately 65 cell generations in culture. Observation of cells in metaphase and anaphase suggests that the interstitial centromere in these dicentrics is non-functional, and that the terminal centromere is solely responsible for their orderly anaphase segregation.

Acrolein↗
PubMed1985

Potential indicators of reproductive toxicity: testicular sperm production and epididymal sperm number, transit time, and motility in Fischer 344 rats.

Comprehensive assessment of the effects of chemicals on male reproductive functioning requires study of effects on spermatogenesis and the quality of spermatozoa produced. As potential indicators of toxic effects, we have examined sperm production rate (SPR) and epididymal sperm numbers, transit time, and motility (percentage motile cells and swimming speeds) in Fischer-344 (F-344) rats. Groups (n = 14 or 15) of rats at 6, 8, 10, 15, and 20 weeks of age were studied to investigate the suitability of these indicators for detecting toxic effects, and to establish the age at which this strain of rat sexually matures. Mean SPRs (10(6) sperm/rat/day), as measured by enumerating spermatids in testicular homogenates, were 2 +/- 3, 22 +/- 6, 41 +/- 7, 49 +/- 6, and 46 +/- 7 at 6, 8, 10, 15, and 20 weeks, respectively. Epididymal sperm numbers and the percentage of motile spermatozoa also increased with age. No correlation was found between SPR and either testis weight or epididymal sperm number at 10, 15, or 20 weeks of age. Our results indicate that male F-344 rats become sexually mature between 10 and 15 weeks of age, and that testis weight and epididymal sperm number are unreliable quantitative indicators of sperm production rate. The low variability among adult rats in SPR and some of the other indicators of testicular and epididymal functioning examined in this study suggest that they should be sensitive measures of male reproductive toxicity.

Age Factors↗