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Biomedical subjects

L Hope

Publications and source records attributed to L Hope.

11 recordsLinked to original sources

Oxidative stress, hepatocellular integrity, and hepatic function after initial reperfusion in human hepatic transplantation.

BACKGROUND: The mechanisms underlying liver graft dysfunction are not completely defined, although much of the injury derives from oxidative stress in organ reperfusion. The antioxidant glutathione in its reduced form (GSH) is an important agent to detoxify oxygen species after reperfusion. However, this effect might be limited by low concentrations at the end of cold storage. The objective of this study was to evaluate GSH and glutathione oxidized (GSSG) hepatic levels pre- and postreperfusion and correlate with hepatocellular injury and liver function in the 5 subsequent days after transplantation. METHODS: Liver biopsies were taken immediately before implant and 2 hours after venous reperfusion in 34 grafts, determining GSH, GSSG levels, and GSSG/GSH ratio. Aminotransferases (ALT, AST) and PT were measured for 5 days. RESULTS: There was a strong decrease in GSH concentration (P <.0001), increase of GSSG levels (P <.01), and increase of the GSSG/GSH ratio (P <.0001). No correlations were found between GSH, GSSG, or GSH/GSSH levels and AST, ALT, and PT. CONCLUSION: Glutathione levels showed significant changes after 2 hours of reperfusion, due to intense oxidative stress. Therapies to replenish GSH should be considered as a protective measure to avoid liver graft dysfunction after transplantation.

Adenosine↗

Genetic evidence supporting the role of peroxisome assembly factor (PAF)-1 in peroxisome biogenesis. Polymerase chain reaction detection of a missense mutation in PAF-1 of Chinese hamster ovary cells.

The peroxisome/plasmalogen-deficient Chinese hamster ovary (CHO) mutant cell line ZR-78.1 contains a missense mutation in its cDNA-encoding peroxisome assembly factor-1 (PAF-1). Using a rapid polymerase chain reaction assay, we now demonstrate that the genome of ZR-78.1 contains only the mutant allele. When mutant ZR-78.1 is fused with wild-type karyoplasts, occasional "negative nuclear hybrids" are observed that lack peroxisomes (Allen, L.-A. H., Morand, O. H., and Raetz, C. R. H. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 7012-7016). Despite the fact that negative nuclear hybrids are tetraploid, they do not contain the wild-type PAF-1 gene, suggesting that a chromosome fragment bearing the wild-type copy of PAF-1 was lost. Negative nuclear hybrids reconstituted with wild-type cytoplasts do contain a wild-type PAF-1 gene, indicating that the cytoplasts somehow reintroduced the wild-type PAF-1 allele without increasing ploidy. These findings support the role of PAF-1 and exclude the hypothesis of an additional cytoplasmic requirement for reinitiation of peroxisome biogenesis in peroxisome-deficient CHO cells. The plasmalogen deficiency and some other biochemical properties of ZR-78.1 are partially corrected in 5-azacytidine-treated subclones. However, such pseudo-revertants do not contain peroxisomes, consistent with the fact that there is no wild-type PAF-1 gene to reactivate by demethylation.

Acyltransferases↗

Production of host shutoff-defective mutants of herpes simplex virus type 1 by inactivation of the UL13 gene.

Two mutants of HSV-1(SC16) carrying disrupted UL13 genes have been generated independently by recombination of wild-type genomic DNA with a plasmid-cloned copy of the UL13 gene containing multiple stop codons. The two mutants were shown to be deficient in UL13 gene expression by Western blotting of infected cells. A revertant virus, in which UL13 expression was restored to a near-normal level, was generated by recombination of one of the UL13-negative mutants with a plasmid carrying the wild-type UL13 gene. The replication of the two UL13-negative viruses in cell culture was somewhat reduced compared to their wild-type parent, and the viruses were unable to produce shutoff of host protein synthesis. The replication of the revertant virus was intermediate between that of the UL13-negative and wild-type viruses, as was its ability to produce host shutoff. Cells infected with the UL13-negative mutants were shown to contain much lower levels than normal of the UL41 gene product, which is known to be required for virion host shutoff. However, there was no significant difference between levels of the UL41 gene product in wild-type and mutant virions. The UL13-negative viruses exhibited different patterns of protein phosphorylation from wild-type virus when infected cells were metabolically labeled with [32P]-orthophosphate and when lysates of infected cells and of virions were subjected to in vitro phosphorylation. However, the UL41 gene product could still be phosphorylated in lysates of UL13-negative virions. We conclude that the UL13 gene is necessary to produce the virion host shutoff effect, but it seems unlikely that the role of UL13 is simply to activate the UL41 gene product by phosphorylation.

Amino Acid Sequence↗

Fatal occupational accidents in Ontario, 1986-1989.

We examined 470 fatal occupational accidents in Ontario, 1986-1989, that met eligibility criteria. Homicides and most accidents on public roads were excluded. Information was obtained from coroners' files and records of the provincial Ministry of Labour. Levels of alcohol likely to produce impairment were found in six subjects (2% of the two-thirds of fatalities tested). Cannabis was detected in 3.9% of cases (17% of those tested), but other illegal drugs were not found. Recommendations of coroner's juries showed that organizational factors were considered relevant on many occasions, although language and literacy were rarely mentioned. The incidence rate rose steadily with age. Other data items were examined, although, because of missing information and/or lack of denominator data for many of them, the conclusions that can be drawn are limited. Among these tentative findings was that more fatal accidents occurred in the first half of the shift than in the second half.

Accidents, Occupational↗

Herpes simplex virus type 1 gene UL13 encodes a phosphoprotein that is a component of the virion.

The UL13 open reading frame of herpes simplex virus type 1 (HSV-1) has been expressed in insect cells by a recombinant baculovirus and in Escherichia coli. In the latter case, the UL13 gene was fused to the gene for glutathione S-transferase (GST) to allow high-level expression of an 80-kDa GST-UL13 fusion protein. Antibody raised against the fusion protein reacted specifically with the 55-kDa UL13 gene product expressed by the recombinant baculovirus. This antibody also recognized a late phosphoprotein in HSV-1-infected cell lysates and a component of purified HSV-1 virions, both with the same electrophoretic mobility as the baculovirus-expressed protein. The virion component was efficiently phosphorylated in vitro by a virion-associated protein kinase. Using the same antibody, the probable homolog of the UL13 gene product was identified in HSV-2-infected cells and purified virions.

Animals↗

Jejuno-ileal bypass for morbid obesity with 24 cm functioning ileum.

26 patients have had jejuno-ileal bypass for morbid obesity. 24 cm of proximal jejunum was anastomosed end-to-side to 24 cm of terminal ileum. Weight loss has been adequate, averaging 70% of ideal weight. Complications have mostly been transient and easily remediable on an out-patient basis. One patient was converted to gastric partitioning because of diarrhea. No other serious complications occurred. The authors recommend further trails with the 24/24 cm version of jejuno-ileal bypass for morbid obesity, complemented with cholecysto-jejunostomy to the proximal end of the excluded small bowel.

Adult↗

Role of adherent T cells and of B cells in the immune response to purified protein derivative of tuberculin.

The role of monocytes, B cells, and adherent and nonadherent T cells in the response of purified protein derivative of tuberculin (PPD) as measured by [3H]thymidine uptake in vitro has been explored. The response to PPD was found to be highly dependent on monocytes, to approximately the same extent as previously found for the responses to concanavalin A (Con A) and phytohemagglutinin. The response to PPD was also found to be highly dependent on a population of adherent T cells different from the adherent T cell population involved in the response to Con A. In the case of PPD, the effect was additive, as opposed to the potentiating effect seen for Con A. Further, the adherent T cells involved in the response to PPD were much more sensitive to hypotonic shock than those in the response to Con A. B cells were also found to be important in the response to PPD, although only to a slight extent.

B-Lymphocytes↗

Role of adherent cells in immune responses to phytohemagglutinin and concanavalin A.

The roles of adherent and nonadherent T cells in the responses to phytohemagglutinin (PHA) and concanavalin A (Con A) were studied. [3H]thymidine uptake by mononuclear cells from human thymus and peripheral blood was used to measure the relative influence of monocytes and B cells on the responses to these mitogens. The response to Con A was dependent on two populations of T cells, one adherent to cotton or nylon and the other nonadherent. The first population appeared to potentiate the latter. In contrast, the response to PHA was dependent only on the nonadherent T cell subpopulation. The responses to PHA and to Con A were both dependent on monocytes to approximately the same extent, but the response to Con A, unlike the response to PHA, was also slightly dependent on B cells.

Cell Adhesion↗

A tale of two tribes.

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Attitude of Health Personnel↗