We'd manage to care more if industry changed its name.
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Biomedical subjects
Publications and source records attributed to C W Bell.
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A gene in equine herpesvirus 1 (EHV-1, equine abortion virus) homologous to the glycoprotein H gene of herpes simplex virus (HSV) was identified and characterised by its nucleotide and derived amino acid sequence. The EHV-1 gH gene is located at 0.47-0.49 map units and contains an open reading frame capable of specifying a polypeptide of 848 amino acids, including N- and C-terminal hydrophobic domains consistent with signal and membrane anchor regions respectively, and 11 potential sites for N-glycosylation. Alignment of the amino acid sequence with those published for HSV gH, varicella zoster virus gpIII, Epstein Barr virus gp85 and human cytomegalovirus p86 shows similarity of the EHV gene with the 2 other alpha-herpesviruses over most of the polypeptide, but only the C-terminal half could be aligned for all 5 viruses. The identical positioning of 6 cysteine residues and a number of highly conserved amino acid motifs supports a common evolutionary origin of this gene and is consistent with its role as an essential glycoprotein of the herpesvirus family. An origin of replication is predicted to occur at approximately 300 nucleotides downstream of the EHV-1 gH coding region, on the basis of similarity to other herpesvirus origins.
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Transcript mapping of the equine herpesvirus 1 (EHV-1) glycoprotein B (gB) gene homologue by Northern blot, S1 nuclease and primer extension analyses indicated that two overlapping transcripts of 3.4 and 4.6 kb originated from the same strand and were transcribed from left to right between coordinates 0.40 and 0.43 of the EHV-1 genome. The 3.4 kb transcript encoded EHV-1 gB and the 5' RNA terminus was located approximately 30 bases downstream from a probable TATA element. The coding region of the gB gene homologue was reconstructed from two subclones using oligonucleotide mutagenesis and inserted into vaccinia virus by homologous recombination. Cells infected with the recombinant virus synthesized EHV-1 gB antigen, which was detectable in the cytoplasm and on the cell surface by immunofluorescence using an EHV-1 neutralizing horse serum and EHV-1 monoclonal antibodies. On Western blots, bands of 138K to 143K, 80K to 90K and 55K to 57K were identified in recombinant virus-infected cells, by both EHV-1 monoclonal antibodies and the polyclonal horse serum. These were similar in Mr to bands identified by these sera in EHV-1-infected cells. Mice vaccinated with the recombinant virus produced antibodies which recognized proteins of the same Mr as EHV-1 gB, on Western blots, but did not have in vitro neutralizing activity.
It was hypothesized that subjects with chronic obstructive pulmonary disease (COPD) receiving long-term oxygen via nasal cannulas have an impaired sense of smell and/or taste. To objectively evaluate the sense of smell and taste, this study used the University of Pennsylvania Identification Test (UPSIT), a 40-item "scratch-n-sniff" test and a 20-item taste test using the four basic taste sensations of sweet, salt, sour, and bitter. Twenty subjects (15 male, 5 female) with severe COPD receiving long-term oxygen therapy (group 1), and an equal number of age- and sex-matched subjects with COPD not receiving oxygen therapy (group 2), and a healthy control group (group 3) were studied. Twelve subjects (seven male, five female) from group 1 subsequently underwent transtracheal oxygen catheter installation. Mean +/- SD for the basic smell test was significantly greater in group 3 (35.35 +/- 3.58) as compared with group 1 (27.70 +/- 6.07) or group 2 (31.10 +/- 4.95) (p less than 0.005). The difference between group 1 and 2 was not significant (p = 0.066). However, when adjusted for pack years of smoking, there were no significant differences between the three groups. Mean +/- SD correct responses for the basic taste test were significantly greater in group 3 (15.75 +/- 1.81) as compared with group 2 (12.8 +/- 2.78) (p less than 0.005) and group 1 (14.00 +/- 2.33) (p less than 0.05). There was no significant difference between group 1 and 2. The corrected data for taste, adjusted for years since quitting smoking, did not alter the basic differences between the groups. Mean smell and taste test scores were essentially unchanged in 12 subjects after six months of transtracheal oxygen therapy. Long-term oxygen use via nasal cannulas in this group of subjects with COPD did not appear to impair their sense of smell and taste. Smoking had a significant but variable effect on the sense of smell and taste.
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We describe the establishment of two human unknown primary tumor (UPT) cell lines and a comparison of their cytogenetic properties with two direct harvests from two tumor biopsy specimens. Histopathological analysis of all four tumor specimens revealed them to be undifferentiated adenocarcinomas of unknown origin. The chromosome numbers in these samples vary between 38 and 144. Consistent structural anomalies involving chromosome 1 were observed in all cases. These included a deletion of the short arm (4 of 4), duplication of 1q (3 of 4) and the presence of homogeneously staining region (2 of 4). Several additional chromosomal changes involving chromosomes 7, 8, and 9 were also observed, but these were less consistent and their importance is not yet clear. Abnormalities in chromosome 1 have generally been associated with advanced malignancy. The finding of consistent chromosome 1 changes in UPT supports our hypothesis that these are type 2 progressors in that benign or less malignant stages are not readily identified. In short, UPT are likely malignant soon after transformation occurs, and this is reflected in their rapid acquisition of the metastatic phenotype and abnormalities in chromosome 1. We are therefore characterizing a number of additional UPT cases to determine if chromosome 1 and other cytogenetic changes are consistently associated with this unique subgroup of tumors.
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A gene in equine herpesvirus 1 (EHV-1; equine abortion virus) equivalent to the gB glycoprotein gene of herpes simplex virus (HSV) has been identified by DNA hybridization and nucleotide sequencing. A 4.3 kbp EHV-1 PstI-ClaI sequence (0.40 to 0.43 map units) contained an open reading frame flanked by appropriate control elements and was capable of encoding a polypeptide of 980 amino acids. This had 50 to 60% identity over a 617 amino acid conserved region with the gB gene products of HSV and three other alphaherpesviruses, and 20 to 30% identity with those of human cytomegalovirus and Epstein-Barr virus. Analysis of the amino acid sequence predicts a long signal peptide, hydrophobic and hydrophilic domains and N-glycosylation sites, and has identified a probable internal proteolytic cleavage site. The EHV-1 gB open reading frame appears to be overlapped at its 5' end by 135 nucleotides of the 3' end of an upstream open reading frame the potential translation product of which has approximately 50% identity with HSV gene ICP 18.5 and VZV gene 30 products.
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We examined various human carcinomas and cells populating a single human neoplasm to determine whether they exhibit a heterogeneous response to the effects of transforming growth factor-beta 1 (TGF-beta). Using recently established human colon carcinoma and renal cell carcinoma under defined in vitro conditions, we observed intertumoral and intratumoral heterogeneity and polarity of responses to TGF-beta (growth inhibition or stimulation) that did not correlate with the metastatic phenotype of the cancer cells as assessed in athymic nude mice. TGF-beta mediated both cytostatic and cytolytic effects against sensitive tumor cells, and these responses were not related to the effects of TGF-beta on the cell-cycle traverse. The human colon carcinoma and renal cell carcinoma, however, exhibited differences in the expression of TGF-beta receptors.
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