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Biomedical subjects

W Marsh

Publications and source records attributed to W Marsh.

At least 73 records · Page 4Linked to original sources
PubMed1987

Orthotopic liver transplantation for alpha-1-antitrypsin deficiency: an experience in 29 children and ten adults.

Thirty-nine patients (29 children and ten adults) underwent OLT for liver disease associated with A1AD from March 1980 to March 1986. Thirty of thirty-six patients (83%) with available data were homozygous phenotype PiZZ. The other six were Pi heterozygotes, being either PiMZ or PiSZ. The mean A1A activity in homozygous and heterozygous patients was 38.8 mg/dL and 114.3 mg/dL respectively. Eight patients died during the first 3 months after OLT (20%). The 5-year actuarial survival is 83% and 60% in pediatric and adult recipients respectively. Today 30 (76%) of the recipients are alive, with follow-ups of 8 to 64 months (average 27 months). The quality of life in the surviving patients is excellent.

Adolescent↗
PubMed1986

Dimethylsulfoxide, retinoic acid and 12-O-tetradecanoylphorbol-13-acetate induce a selective decrease in the phosphorylation of P150, a surface membrane phosphoprotein of HL60 cells resistant to adriamycin.

Studies have been carried out to analyze protein phosphorylation in membranes isolated from adriamycin resistant HL60 cells which have been grown for various time periods in the presence of dimethylsulfoxide (DMSO), retinoic acid (RA) or 12-O-tetradecanoylphorbol-13-acetate (TPA). The results show that membranes isolated from cells treated with these agents are defective in the phosphorylation of P150, a membrane phosphoprotein associated with drug resistance in HL60 cells. This response is highly selective since only a few membrane proteins show decreased phosphorylation levels under these conditions. Magnesium dependent protein kinase activity in membranes from cells treated with DMSO, RA or TPA is not altered relative to untreated membranes under conditions where there is a major decrease in P150 phosphorylation. Additional studies also show that treatment of resistant cells with TPA results in a major decrease in the in vivo phosphorylation of P150. These results thus demonstrate that agents capable of inducing differentiation in HL60 cells can selectively modulate the phosphorylation of P150. This system should be of value in clarifying mechanisms involved in the phosphorylation of this protein.

Dimethyl Sulfoxide↗
PubMed1986

Isolation and characterization of adriamycin-resistant HL-60 cells which are not defective in the initial intracellular accumulation of drug.

Two human leukemia cell lines (Molt-4 and HL-60) have been used for establishing cells which exhibit a low level resistance to Adriamycin. Analysis of drug uptake patterns shows that the Molt-4 resistant cells are defective in the initial intracellular accumulation of drug. In contrast to Molt-4 the levels of drug which accumulate in the sensitive and resistant HL-60 cells during a 60-min incubation period are essentially the same. However, when incubations are continued there is a major reduction in intracellular drug levels in the resistant cell. Further studies show that resistant cells incubated in the presence of drug for extended time periods efflux drug at a rate considerably greater than that exhibited by the sensitive parent line. Similar efflux patterns are obtained with nuclei isolated from drug-sensitive and -resistant cells. Additional studies using an in vitro phosphorylation system demonstrate distinct protein changes in membranes of Molt-4 and HL-60 resistant cells. Thus, we have found that a membrane fraction from the Molt-4 resistant line contains a Mr 170,000 protein which is not detected in a similar fraction from cells sensitive to drug. HL-60 resistant membranes contain two proteins with molecular weights of 150,000 and 120,000 which are also not found in membranes from drug-sensitive cells. The results of this study suggest that drug resistance in HL-60 cells is related to an efflux mechanism which is triggered only after cells are exposed to drug for prolonged periods.

Cell Line↗
PubMed1985

Evidence for the involvement of two distinct membrane proteins in adriamycin resistance in Chinese hamster lung cells.

Chinese hamster lung cells resistant to Adriamycin were labeled with inorganic [32P]orthophosphate and thereafter incubated with low levels of N-ethylmaleimide. Plasma membranes and endoplasmic reticulum were isolated and the phosphorylated proteins were analyzed after polyacrylamide gel electrophoresis. The results demonstrate that both plasma membranes and endoplasmic reticulum from resistant cells contain two highly phosphorylated proteins [Mr 180,000 (p180) and Mr 220,000 (p220)] which are present in very low levels in these membrane fractions prepared from drug sensitive cells. p220 is present in much higher levels in the endoplasmic reticulum as compared to the plasma membranes whereas p180 is equally distributed in these two membrane fractions. When resistant cells revert to drug sensitivity there is a parallel loss in the phosphorylation levels of p180 and p220. Labeling of membrane proteins with 125I in the presence of chloramine-T also reveals that p180 and p220 are present in significantly greater levels in resistant membranes as compared to similar fractions prepared from drug sensitive cells. Partial digests of phosphorylated p180 and p220 produced with chymotrypsin or V8 protease reveal that each protein has a distinct phosphopeptide pattern. Both p180 and p220 are phosphorylated exclusively at serine residues. The results of this study therefore suggest that resistance to Adriamycin in Chinese hamster lung cells requires the involvement of two distinct proteins which are both bound to cell membranes.

Animals↗
PubMed1984

Modulation of the late asthmatic response by antigen-specific immunoglobulin G in an animal model.

The late asthmatic response (LAR) occurs 4 to 12 h after antigenic challenge and has been related to the severity of asthma. In addition, improvement of asthmatic symptoms after immunotherapy has also been related to loss of the LAR. Because the LAR seems to be a critical component of asthma, we employed an animal model of the LAR to study its immunopathogenesis, concentrating on the role of antigen-specific rabbit homocytotropic (IgE) and heterocytotropic (IgG) antibodies to Alternaria tenuis. Serum samples from rabbits previously immunized with Alternaria extract were infused into age-matched previously nonimmunized recipients. Groups of recipients were categorized according to the immune status of the transfused serum: E-only, E/G, subdivided into E/low G (1:256 to 1:512) and E/high G 1:2,048), G (serum heat-treated to minimize IgE), and Control (transfused with serum from nonimmunized rabbits). Subsequently, pulmonary function was measured before and for 6 h after challenge with aerosolized Alternaria tenuis by recording pulmonary resistance, functional residual capacity by helium dilution, specific conductance, and dynamic compliance. The E-only recipients showed an immediate asthmatic response followed by a marked LAR comparable in magnitude to actively immunized animals. The E/G recipients showed blunting of the LAR in a dose-dependent fashion, with increasing titers of IgG antibody. The G recipients showed no immediate or late responses. Immunofluorescent studies in selected animals from each group failed to show any granular deposition of immunoglobulin or C3 in either the airways or blood vessels of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Improvements in hepatic parenchymal transection for living related liver donor.

INTRODUCTION: To eliminate mortality and morbidity risk in living related liver donors, we developed a new surgical technique to resect hepatic parenchyma using an ultrasonic surgical aspirator in association with a monopolar floating ball cautery. METHODS: We performed 17 right hepatectomies and 2 left hepatectomies using this technique. We performed a retrospective analysis of perioperative mortality, length of hospitalization (LOS), blood transfused during surgery (IBT), intraoperative blood lost (IBL), biliary complications (BC), and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) peak in the first postoperative week. This group of patients (Group A) was compared, using the analysis of variance (ANOVA) test (P < .05) with 2 different groups of 19 patients: Group B with liver neoplasms that had the same technique as Group A, and Group C wherein a crushing clamp technique was used. RESULTS: All of the analyzed variables showed significative statistical differences, especially between Group A and Group C (IBL, P < .000; IBT, P < .006; LOS, P < .028; BC, P < .000; AST peak, P < .041; and ALT peak, P < .023). DISCUSSION: The association of these 2 techniques seems to reduce the LOS, and the need for intraoperative blood transfusions. Moreover, the surgical complications (biliary leaks) and the postoperative parenchymal cytonecrosis seem to be less using this technique.

Adult↗
PubMedDate not supplied

Prevalence of psychiatric disorders in patients with irritable bowel syndrome.

Thirty-five patients with irritable bowel syndrome were referred from the gastroenterology service and underwent structured psychiatric interviews to assess the prevalence of psychiatric illness. Thirty-three (94%) of 35 patients were found to have a lifetime prevalence of any Axis I disorder; the predominant diagnoses were mood and anxiety disorders. Theoretical and practical implications of these findings are discussed.

Adult↗