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Biomedical subjects
Publications and source records attributed to J Smith.
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The complete sequence of Punta Toro virus (Phlebovirus, Bunyaviridae) middle size (M), RNA has been determined. The RNA is 4330 nucleotides long (mol wt 1.46 X 10(6), base composition: 26.7% A, 33.6% U, 18.5% G, 21.2% C) and has 3'- and 5'-terminal sequences that, depending on the arrangement, are complementary for some 15 residues. The viral RNA codes in its viral-complementary sequence for a single primary gene product (the viral glycoprotein precursor) that is comprised of 1313 amino acids (146,376 Da) and is abundant in cysteine residues but has few potential asparagine-linked glycosylation sites. The 5'-noncoding region of the Punta Toro M viral-complementary RNA is short (16 nucleotides); the 3'-noncoding sequence is much longer (372 nucleotides). The latter is rich in short stretches of adenylate residues, like the 3'-noncoding regions of the Punta Toro S mRNA species (T. Ihara, H. Akashi, and D. H. L. Bishop, 1984, Virology 136, 293-306). No other large open reading frame has been identified in either the viral, or viral-complementary, M RNA sequences. Limited amino-terminal sequence analyses of the two viral glycoproteins have indicated the gene order and potential cleavage sites in the glycoprotein precursor. The data suggest the existence of a 30 X 10(3)-Da polypeptide (designated NSM) in the glycoprotein precursor that precedes the G1 protein (i.e., gene product order: NSM-G1-G2). Examination of the sequence of the Punta Toro M gene product reveals the presence of multiple hydrophobic sequences including a 19-amino acid, carboxy-proximal, hydrophobic region (G2). This hydrophobic sequence is followed by a 13-amino acid-terminal sequence rich in charged amino acids. The size and constitution of the carboxy-terminal region is consistent with a transmembranal and anchor function for the glycoprotein in the viral envelope. Other regions of the glycoprotein precursor contain sequences of amino acids with a predominantly hydrophobic character (23, 50, and 20 amino acids in length). Their functions are unknown. The amino terminus of the G1 protein is located near the end of the 23-amino acid-long hydrophobic sequence of the presumptive precursor, the hydrophobic 50-amino acid sequence lies within G1, and the amino terminus of G2 is located in the middle of the 20-amino acid-long hydrophobic sequence.(ABSTRACT TRUNCATED AT 400 WORDS)
The health care industry in general and hospitals in particular face an uncertain future as the federal government moved with unusual speed to enact sweeping Medicare legislation. These changing patterns of reimbursement reverse key economic incentives by which hospitals have been driven since the federal program for the elderly began 18 years ago. "Reasonable" cost reimbursement has been replaced by a policy that requires Medicare to establish and fix prices in advance, on a cost-per-case basis, using as a measure 467 categories called "diagnosis-related groups." These changes will present new challenges for the health care industry and will need innovative approaches to meet them. The prospective pricing system attempts to reverse the escalation of health care costs. Under this system, hospitals can realize greater profits only by reducing costs, not by incurring them. The prospective payment system will have profound effects on the practice of infectious diseases, and the potential impact on hospitals, the pharmaceutical industry, physicians, and patients will have to be studied in detail.
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The injection of mice with 800 micrograms of an affinity-purified goat antibody to mouse IgD (GaM delta) induces early, T-independent polyclonal increases in the expression of B cell surface Ia, and B cell size and DNA synthesis, as well as later, T-dependent polyclonal increases in spleen cell number and Ig secretion. We have now studied the effects of varying the doses of injected GaM delta on all phases of B cell activation, as well as the effects of supplementing GaM delta with varying quantities of normal goat IgG (GIgG). We have found that while 12.5 micrograms of GaM delta modulates most of the IgD from the surface of splenic B lymphocytes, it fails to activate these cells. Increases in the expression of B cell surface Ia are first seen when 50 micrograms of GaM delta is injected, while increases in B cell DNA synthesis usually require the injection of 200 micrograms of GaM delta and peak with doses of approximately 800 micrograms. Increases in splenic B cell number and DNA synthesis during the T-dependent phase of GaM delta-induced B cell activation are seen only in those mice that were injected with sufficient quantities of GaM delta to induce DNA synthesis during the T-independent phase. Supplementing the dose of GaM delta injected with additional GIgG has no significant effect on B cell DNA synthesis or B cell number but dramatically increases polyclonal IgG1 secretion. Although mice which have been injected with 50 micrograms of GaM delta or with 800 micrograms of GIgG alone have few polyclonal IgG1-secreting cells, substantial increases in the number of IgG1-secreting cells are seen in mice injected with 50 micrograms of GaM delta plus 750 micrograms of GIgG. GIgG and larger doses of GaM delta similarly act synergistically to increase polyclonal IgG1 secretion. In contrast to the induction of polyclonal IgG1 secretion, the stimulation of polyclonal IgM secretion requires the injection of mitogenic doses of GaM delta and is not enhanced by the injection of additional GIgG. These observations suggest that, in this model system, stimulatory signals that activate B cells through their surface Ig are limiting for the induction of polyclonal proliferation and IgM secretion, while the generation of T helper lymphokines that do not directly interact with B cells through their surface Ig may be more limiting for the stimulation of polyclonal IgG1 secretion.
We have previously shown that the mouse c-H-ras gene acquires transforming activity in chemically induced skin tumours. We have now investigated the pattern of DNA methylation at HpaII and XhoI sites around the c-H-ras locus in various tissues and stages of epidermal tumour progression. The results of this study suggest a correlation between the methylation state of the c-H-ras gene and its susceptibility to oncogenic conversion by a point-mutation. The locus is substantially undermethylated in normal epidermis in comparison with NIH/3T3 fibroblasts. Intermediate levels of methylation were observed in the other tissues investigated. The undermethylation at HpaII sites in epidermal DNA persists through the morphologically distinct phases of hyperplasia, benign papilloma and malignant carcinoma. Methylation at a specific XhoI site close to the c-H-ras gene is significantly reduced with respect to normal epidermis in some, but not all epidermal tumours. The methylation state of the c-H-ras locus in specific tumours is stably maintained following transfection of these DNAs into NIH/3T3 cells and selection of transformed foci. Demethylation of the locus is not essential in vitro for the transforming activity of DNA from epidermal tumours. The significance of changes in the methylation pattern of the c-H-ras gene in different tissues and during tumour progression is discussed.
The nucleotide sequences of a 1279-bp sheep elastin cDNA clone, pcSEL1 [Yoon et al. (1984) Biochem. Biophys. Res. Commun. 118, 261-269], and a 1230-bp sheep elastin genomic subclone, pSS1 [Davidson et al. (1984) Biochem. J. 220, 643-652], corresponding to a portion of the cDNA clone, were determined. These analyses permitted determination of the 100 amino acids at the carboxy terminus of sheep tropoelastin. A portion of this sequence showed strong homology to known sequences of pig tropoelastin, but most of the sequence had not been previously determined through protein sequencing. Novel aspects of the tropoelastin molecule which have been revealed by the present analyses are (i) the presence of an unusual sequence, KPPKP, which may contribute to crosslink formation; and (ii) the finding of cysteine within a sequence, CLGKSCGRKRK, at the putative carboxy terminus of tropoelastin. Because of the presence of these sequences, it is speculated that the carboxy-terminal region may be of importance in crosslinking tropoelastin molecules to themselves or to other matrix macromolecules. The nucleotide analyses revealed that sheep elastin mRNA contains a 974-bp untranslated sequence at the 3' end, which appears to be strongly conserved among species.
We report on a study of the cytogenetic and hepatotoxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mice of the C57B1/6J (with high-affinity TCDD receptor) or DBA/2J (with low-affinity TCDD receptor) strains were given single intraperitoneal injections of 50, 100 or 150 micrograms of TCDD/kg body weight. At various times (8-48 h) after injection, we examined bone marrow cells for cytogenetic effects by performing structural aberration, sister-chromatid exchange, and micronucleus tests. 1 month after exposure, liver sections were studied for hepatotoxic effects. We found no evidence of chromosome damage by TCDD given in doses that cause liver damage in both strains of mice.
Patients referred to a centralized glaucoma laboratory obtained intraocular pressure measurements every two hours from 5:00 am to 3:00 pm. Analysis revealed 400 eyes with visual field defects and 400 eyes without visual field defects as determined by Octopus perimetry of the central 20 degrees. The diurnal variation in intraocular pressure was 6.2 mmHg +/- 3.6 for those with visual field defects and 5.5 mmHg +/- 2.7 for those without visual field defects. There was no statistical significance in the mean diurnal variation between the two groups (P = 0.91). The highest intraocular pressure tended to occur at either 5:00 am to 7:00 am or 11:00 am to 1:00 pm in both groups. The lowest intraocular pressure tended to occur between 7:00 am to 9:00 am or 1:00 pm to 3:00 pm in both groups. No significant differences were noted in the distribution between the two groups with regard to the time of the highest or lowest intraocular pressure. In the group with visual field defects, 30% had an intraocular pressure of less than 23 mmHg and 23% had an intraocular pressure of greater than or equal to 23 mmHg at all five time periods.
To estimate the risk of hepatitis B virus (HBV) infection among hospital workers, we measured the prevalence of HBV infection in employees in five hospitals in different parts of the country and examined the effect of occupational and non-occupational factors on HBV prevalence. Among 5,697 persons studied, serologic markers of HBV infection were found in 807 (14%). Prevalence of infection was strongly related to race (Asian greater than Black greater than White), sex (male greater than female) and increasing age. Risk related to health occupation, studied by examining the change in HBV prevalence with duration in occupational group, was most strongly correlated with frequency of contact with blood during work. Workers having frequent blood contact had the highest estimated infection rate (1.05 per 100 person-years) and those with moderate contact an intermediate infection rate, compared to a negligible infection rate in workers with no blood contact. Frequency of needle accidents had an independent, positive effect on HBV infection rates, while degree of patient contact had no effect. Infection risk was uniform among all hospitals for groups with frequent blood contact. Among different occupation groups, risk of HBV infection also correlated closely with degree of blood-needle contact during daily work. This study provides a general approach to assessing risk of HBV infection in hospital personnel, and indicates that risk may be most easily estimated by quantitating degree of blood-needle contact during daily work.