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Biomedical subjects

T L Wright

Publications and source records attributed to T L Wright.

At least 127 records · Page 7Linked to original sources
PubMed1991

Persistent hepatitis B virus following interferon alfa therapy and liver transplantation.

A 44-year-old man with chronic hepatitis B virus infection and cirrhosis was treated with recombinant human interferon alfa for 67 days immediately before orthotopic liver transplantation and immunoprophylaxis with hyperimmune globulin to hepatitis B virus in the peritransplant period. Dot blots for hepatitis B virus DNA demonstrated marked reduction in viremia after 41 days of interferon alfa treatment. Southern analysis for hepatitis B virus in liver showed a pronounced decrement in actively replicating forms in the explant, although hepatic infection was still detectable. After liver transplantation, tests for serum hepatitis B virus DNA and hepatitis B surface antigen remained negative. The patient died 32 days after transplantation of causes unrelated to hepatitis B virus. DNA isolated from liver and other visceral organs at autopsy showed infection of the engrafted liver and the persistence of monomeric relaxed circular forms of hepatitis B virus DNA in pancreas, kidney, and spleen. Thus, graft reinfection occurred despite aggressive antiviral therapy and immunoprophylaxis combined with liver transplantation. Existing viral serological markers appear insufficiently sensitive to assess residual infectivity.

Adult↗
PubMed1991

Hepatitis C in liver transplant recipients.

HCV infection is commonly found in patients with chronic liver disease undergoing liver transplantation. However, the presence of antibody to HCV does not appear to be associated with the development of hepatitis posttransplant. No other risk factors were identified that appear to predispose patients to development of hepatitis in the posttransplant period, including amount of blood product exposure. The role of immunosuppression in the acquisition and expression of liver disease caused by HCV remains to be determined.

Hepacivirus↗
PubMed1990

Mechanisms of transport of nontransferrin-bound iron in basolateral and canalicular rat liver plasma membrane vesicles.

Although most iron in plasma is bound to transferrin, recent evidence suggests that the nontransferrin-bound fraction contributes to hepatic iron loading and toxicity seen in iron-overload disorders. Our studies of isolated perfused rat liver previously demonstrated saturable uptake of nontransferrin-bound iron that continues despite hepatic iron overload. To further characterize the mechanism of transport of this form of iron, we measured binding of 55Fe-labeled ferrous ascorbate to rat liver plasma membrane vesicles under varying conditions. Binding of 5 mumol/L iron by both basolateral and canalicular membranes was time-dependent and linear for the first 5 sec. Initial rate of binding of ferrous ascorbate to basolateral membrane vesicles was temperature dependent and increased by calcium but, in contrast to the perfused rat liver, was not inhibited by other divalent cations. Binding velocities by basolateral membrane vesicles were saturable at increasing iron concentration (Km = 33 mumol/L, Vmax = 16 pmol/mg protein/sec). Ferrous iron binding by canalicular membrane vesicles was also temperature dependent, but initial association rates were not saturable over the concentration range studied (2 to 20 mumol/L). We conclude that nontransferrin-bound iron associates with basolateral liver plasma membrane vesicles by a saturable mechanism sensitive to temperature and calcium and consistent with a membrane carrier. Other divalent cations do not inhibit membrane association but may compete for a subsequent cytosolic binding site.

Animals↗
PubMed1989

Age differences in coping: does less mean worse.

Previous research suggests that elderly people utilize fewer coping strategies than younger people. Some researchers suggest that these quantitative changes reflect decreases in the use of maladaptive strategies; others contend that they reflect decreases in the use of adaptive strategies by older adults. The present article reports the findings of three studies of coping in older people, two addressing coping with health problems, and the other addressing coping with moving. In all three studies, the number of self-reported coping strategies decreases with age. Results do not support the idea that decreases in the number of strategies imply decrements in the quality of coping, however: in two studies, age was unrelated to the effectiveness of strategies, in the third, effectiveness ratings were higher for older subjects. The need for evaluation of specific outcomes of coping strategies is discussed, along with the need for task-specific measurement of coping. It is proposed that decreases in the number of coping strategies reflect improved coping efficiency, rather than a deterioration of adaptational skills.

Adaptation, Psychological↗
PubMed1988

Non-transferrin-bound iron uptake by rat liver. Role of membrane potential difference.

Non-transferrin-bound iron is efficiently cleared from serum by the liver and may be primarily responsible for the hepatic damage seen in iron-overload states. We tested the hypothesis that transport of ionic iron is driven by the negative electrical potential difference across the liver cell membrane. Extraction of 55Fe-labeled ferrous iron (1 microM) from Krebs bicarbonate buffer by the perfused rat liver was continuously monitored as the transmembrane potential difference (measured using conventional microelectrodes) was altered over the physiologic range by isosmotic ion substitution. Resting membrane potential in Krebs bicarbonate buffer was -28 +/- 1 mV. Perfusion with 1 microM ferrous iron caused a reversible 3 +/- 1 mV depolarization, and higher concentrations of iron caused even greater depolarization. Conversely, depolarization of the liver cells consistently reduced iron extraction. Replacement of sodium with potassium (70 mM) or choline (131 mM) depolarized the hepatocytes to -15 and -20 mV and decreased iron extraction by 28 and 31%, respectively. Perfusion with bicarbonate-free solutions containing tricine buffer (10 mM) reduced the membrane potential to -23 mV and reduced iron extraction by 18%. In contrast, the high basal extraction of iron (91.1 +/- 1.4%) was not further increased by substitution of nitrate for chloride (-46 mV) or infusion of glucagon (-34 mV). All effects were reversible, suggesting that perfusion with 1 microM iron produced little toxicity. These findings are consistent with an electrogenic transport mechanism for uptake of non-transferrin-bound iron that is driven by the transmembrane potential difference.

Animals↗
PubMed1988

Uptake and metabolism of polymerized albumin by rat liver. Role of the scavenger receptor.

Hepatitis B virus binds avidly to albumin polymers, which in turn may mediate viral attachment to liver cells. This hypothesis is critically dependent on prior results obtained using glutaraldehyde-polymerized human serum albumin as a model for naturally occurring albumin species. We used the perfused rat liver to characterize the uptake, cellular distribution, and metabolism of glutaraldehyde-polymerized human albumin. 125I-glutaraldehyde-polymerized human albumin was efficiently removed from the perfusate by the liver (29% extraction). However, few autoradiographic grains were located over hepatic parenchymal cells (6%). Instead, most glutaraldehyde-polymerized human albumin appeared to be removed by endothelial (59%) or Kupffer (31%) cells. Hepatic uptake was strongly inhibited by formaldehyde-treated monomeric albumin, a known ligand of the endothelial scavenger receptor for chemically modified proteins. After uptake, most glutaraldehyde-polymerized human albumin was rapidly degraded and released into the perfusate (74% within 60 min). This process was blocked by chloroquine and leupeptin, suggesting that it involves lysosomal acid hydrolases. We conclude that glutaraldehyde-polymerized albumin is efficiently cleared and degraded by the endothelial scavenger pathway. Glutaraldehyde-polymerized albumin therefore appears to be a poor model for predicting the hepatic handling of naturally occurring albumin species bound to hepatitis B virions. Even if viral particles were to follow this pathway, few would enter parenchymal hepatocytes.

Animals↗
PubMed1988

Hepatic efflux of glutathione by the perfused rat liver: role of membrane potential difference.

Glutathione (GSH) is released into hepatic sinusoids by a carrier-mediated process. The importance of transmembrane potential difference (PD) as a driving force for hepatic efflux of GSH from isolated perfused rat liver was investigated. The membrane PD was measured using intracellular microelectrodes as PD was altered over the physiological range by ion substitution in the perfusate. The effect of a change in membrane PD on the rate of efflux of GSH into the perfusate was determined. Because GSH carries a net negative charge at physiological values of pH, we predicted that hyperpolarization of cells would increase efflux, whereas depolarization would decrease efflux. Three different manipulations were used to depolarize the hepatocyte membrane to a similar degree, and variable effects on GSH efflux were observed. Substitution of Cl with gluconate in the perfusate depolarized the hepatocyte but had no effect on GSH efflux, whereas substitution of Na with choline in the perfusate increased GSH efflux to 110% of basal values. Perfusion with K+ inhibited GSH efflux by 21%. The latter two manipulations were associated with evidence of hepatic injury. Hyperpolarization of the hepatocyte also had variable effects on GSH efflux. Substitution of Cl with nitrate in the perfusate transiently increased the membrane PD and decreased GSH efflux, whereas perfusion with glucagon caused a sustained increase in membrane PD but did not alter GSH efflux rates. None of the latter manipulations was associated with hepatic injury and thus no consistent relationship between membrane PD and sinusoidal efflux of GSH was demonstrated. We conclude that in the isolated perfused rat liver, efflux of GSH is not driven directly by membrane PD.

Animals↗
PubMed1987

A social relations model test of Sullivan's anxiety hypothesis.

Interpersonal relationships and mutual influence are important aspects of both personality and behavior. However, empirical tests of mutual influence in anxiety have not occurred because of difficulties in design and assessment. In this report, we present a study of two training groups of graduate students and a study of an outpatient psychotherapy group. In both studies relationship-specific variance was significant and accounted for a substantial proportion of the systematic variance. In the training groups, there were also significant individual differences in experienced anxiety. These studies support the importance of relationships in anxiety but not Sullivan's hypothesis of the exclusive interpersonal nature of anxiety (Sullivan, 1964). The results address Endler and Magnusson's (1976a, 1976b) interactional approach to anxiety by assessing dynamic interaction rather than mechanistic interaction. In addition, these studies extend the use of the Social Relations Model to a new area, anxiety, and demonstrate its use in separating relationship-specific adjustments in anxiety from individual differences in anxiety.

Adjustment Disorders↗
PubMed1986

Characterization of non-transferrin-bound iron clearance by rat liver.

Recent evidence suggests that the hepatic iron-loading characteristic of hemochromatosis may result in part from efficient hepatic clearance of non-transferrin-bound iron, which is increased in this disorder. However, this hypothesis assumes that hepatic clearance remains highly efficient despite excess iron stores. We therefore studied hepatic uptake of non-transferrin-bound iron in the single-pass perfused rat liver under varying conditions. Animals were iron loaded or depleted by dietary manipulation, but no changes in the efficiency of ferrous iron uptake or the kinetic parameters were seen (single-pass extraction, 59-74%; Km, 16-19 microM; Vmax, 30-32 nmol X min-1 X g liver-1). Added divalent zinc, cobalt, and manganese ions reversibly inhibited ferrous iron uptake and the inhibition by zinc was shown to be competitive. Uptake required calcium, was markedly temperature-sensitive (delta E = 14.3 Kcal/mol), and was relatively insensitive to inhibition of cellular energy metabolism. Particles consistent with ferritin cores were seen in lysosomes of hepatic parenchymal cells within 30 min of perfusion with ferrous iron. These results suggest that ferrous iron is cleared from plasma by a passive, saturable transport process that is not regulated by the iron content of the liver and that may be shared with other transition metal ions. Because clearance is highly efficient, increased levels of non-transferrin-bound iron in plasma may present the liver with an obligatory iron load resulting in progressive accumulation and toxicity.

Anaerobiosis↗
PubMed1985

Gastrointestinal Kaposi's sarcoma in patients with acquired immunodeficiency syndrome. Endoscopic and autopsy findings.

Homosexual men with acquired immunodeficiency syndrome and Kaposi's sarcoma (KS) have been studied to define the extent of gastrointestinal KS. In 50 patients examined by both upper endoscopy and flexible fiberoptic sigmoidoscopy, 20 (40%) had visible lesions consistent with KS. Ten patients (20%) had upper and lower tract involvement, 6 (12%) patients had upper tract involvement alone, and 4 (8%) had lower tract disease alone. Only 23% of endoscopic biopsies of KS lesions were positive for KS. Gastrointestinal KS was not more frequent in patients with nodal KS (41%) than in patients with skin KS (50%). No clinical sequelae of gastrointestinal KS lesions were seen. Mortality was significantly greater in those patients with endoscopic evidence of gastrointestinal KS. Postmortem examination of 13 men with KS and acquired immunodeficiency syndrome revealed abdominal visceral involvement in 10 patients (77%). Antemortem endoscopic findings correlated with subsequent autopsy data in 5 patients. Our findings suggest that visceral involvement, though rarely symptomatic, may be associated with a poorer prognosis.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Efficient clearance of non-transferrin-bound iron by rat liver. Implications for hepatic iron loading in iron overload states.

In hemochromatosis and other disorders associated with iron overload, a significant fraction of the total iron in plasma circulates in the form of low molecular weight complexes not bound to transferrin. Efficient and unregulated clearance of this form of iron by the liver may account for the hepatic iron loading and toxicity that characterize these diseases. We tested this possibility by examining the hepatic removal process for representative iron complexes in the single-pass perfused rat liver. Hepatic uptake of both ferrous and ferric 55Fe from ultrafiltered human serum was found to be highly efficient and effectively irreversible (single-pass extraction of 1 microM iron, 58-75%). Similar high efficiencies were seen for iron complexed to specific physiologic and nonphysiologic coordinators, including histidine, citrate, fructose, oxalate and glutamate, and tricine. Because of lower plasma flow rates, single-pass extraction of these iron complexes in vivo should be even greater. Autoradiography confirmed that most iron had been removed by parenchymal cells. Hepatic removal from Krebs-tricine buffer was saturable with similar kinetic parameters for ferrous and ferric iron (apparent Km, 14-22 microM; V max, 24-38 nmol min-1 g liver-1). These findings suggest that high levels of non-transferrin-bound iron in plasma may be an important cause of hepatic iron loading in iron overload states.

Anaerobiosis↗
PubMed1984

Listeners' discrimination of real and human-imitated animal sounds.

To determine if listeners can accurately distinguish between real and human-imitated animal sounds, a total of 165 recorded sounds (55 real and 110 human-imitated) of cats, cows, dogs, pigs, and sheep were randomly arranged on a master tape and presented to 30 listeners for discriminative judgments. Results indicate that, in general, listeners can accurately discriminate real from human-imitated animal sounds. Suggestions for future research are discussed.

Animals↗
PubMed1983

Self-efficacy expectancies, outcome expectancies, and the persistence of pain control in childbirth.

Bandura's (1977) self-efficacy theory of mastery behavior distinguishes self-efficacy expectancies from outcome expectancies. The relative roles of self-efficacy expectancies, outcome expectancies, and importance were studied as predictors of persistence of pain control in medication-free childbirth. Fifty-two primiparous women made self-efficacy judgments before and during labor and then reported in postdelivery interviews the timing and amount of medication use during labor and delivery. Self-efficacy expectancies predicted persistence in pain control without medication better than outcome expectancies, importance, and seven other alternative predictors, supporting several aspects of construct validation of the self-efficacy expectancy construct. However, self-efficacy and outcome expectancies were very highly correlated and largely redundant in their correlations with mastery. Three possible reasons and implications for the lack of differentiation of self-efficacy and outcome expectancies are discussed.

Adult↗