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Biomedical subjects

R Wright

Publications and source records attributed to R Wright.

At least 19 recordsLinked to original sources

Reversible inhibition of albumin production by rat hepatocytes maintained on a laminin-rich gel (Engelbreth-Holm-Swarm) in response to secretory products of Kupffer cells and cytokines.

Decreased albumin synthesis by hepatocytes in liver injury is thought to occur in response to Kupffer cell-derived acute-phase cytokines. In this study we used hepatocytes maintained in a differentiated phenotype, by culture on a laminin-rich gel substratum (Engelbreth-Holm-Swarm matrix), to investigate the effects of Kupffer cell-conditioned medium and purified cytokines (interleukin-1, interleukin-6 and tumor necrosis factor-alpha) on albumin synthesis. Kupffer cell-conditioned medium caused a reversible decrease in albumin synthesis to 64.7% of control (p less than 0.01, Wilcoxon's rank sum test, n = 11) on day 2. Repeated doses caused further dose-dependent reversible responses. The same result was obtained when protease inhibitors (alpha 1-antitrypsin and alpha 2-macroglobulin) were added to Kupffer cell-conditioned medium (n = 3), thus eliminating the potential effect of matrix degradation. Pure interleukin-1, interleukin-6 and tumor necrosis factor-alpha also inhibited albumin synthesis (p less than 0.05, Wilcoxon's rank sum test, n = 5), interleukin-6 having the greatest effect. After exposure to interleukin-1 (30 U.ml-1) and tumor necrosis factor-alpha (300 U.ml-1), decreased albumin synthesis was followed by a rebound increase (n = 3). Our results support the hypothesis that reduced albumin synthesis in the acute-phase response is modulated by cytokines released from Kupffer cells. Moreover, our results suggest that hepatocytes may exhibit a compensatory increase in albumin synthesis after cytokine withdrawal. These findings may be of physiological importance in the recovery from injury and the acute-phase response in vivo.

Albumins

Mutation of a tyrosine localization signal in the cytosolic tail of yeast Kex2 protease disrupts Golgi retention and results in default transport to the vacuole.

Kex2 protease processes pro-alpha-factor in a late Golgi compartment in Saccharomyces cerevisiae. The first approximately 30 residues of the 115 amino acid CO2H-terminal cytosolic tail (C-tail) of the Kex2 protein (Kex2p) contain a Golgi retention signal that resembles coated-pit localization signals in mammalian cell surface receptors. Mutation of one (Tyr713) of two tyrosine residues in the C-tail or deletion of sequences adjacent to Tyr713 results in loss of normal Golgi localization. Surprisingly, loss of the Golgi retention signal resulted in transport of C-tail mutant Kex2p to the vacuole (yeast lysosome), as judged by kinetics of degradation and by indirect immunofluorescence. Analysis of the loss of Kex2 function in vivo after shutting off expression of wild-type or mutant forms proved that mutations that cause rapid vacuolar turnover do so by increasing the rate of exit of the enzyme from the pro-alpha-factor processing compartment. The most likely explanation for these results is that mutation of the Golgi retention signal in the C-tail results in transport of Kex2p to the vacuole by default. Wild-type Kex2p also was transported to the vacuole at an increased rate when overproduced, although apparently not due to saturation of a Golgi-retention mechanism. Instead, the wild-type and C-tail mutant forms of Kex2p may follow distinct paths to the vacuole.

Amino Acid Sequence

Discriminators of willingness to consider cadaveric kidney donation among black Americans.

Black Americans were classified as either willing or unwilling to consider serving as kidney donors according to a combination of demographic and social psychological variables. Findings indicated that, in addition to selected religious variables, willingness to consider donation was associated with gender, age, source of information about organ donation, perceived need for transplants among blacks, self-acceptance of transplant organs and perception of bias in the selection of transplant recipients. Implications of the findings for social work practice and future research are discussed.

Adolescent

Complementation between Sindbis viral RNAs produces infectious particles with a bipartite genome.

Sindbis virus, the type member of the alpha-viruses, is an enveloped virus containing a nonsegmented positive-strand RNA genome. We show that the nonstructural and the structural genes can function to produce infectious virus particles when they are expressed on two different RNA segments. The nonstructural genes are translated from an RNA in which the structural genes have been replaced by the chloramphenicol acetyltransferase gene [Xiong, C., Levis, R., Shen, P., Schlesinger, S., Rice, C. M. & Huang, H. V. (1989) Science 243, 1188-1191]. The structural genes are encoded in a defective-interfering RNA but are translated from a subgenomic RNA. Both segments contain the cis-acting sequences required for replication and packaging and are copackaged. This type of genome provides a model for an ancestral intermediate between alphaviruses and the multipartite positive-strand RNA viruses of plants. These different viruses show sequence similarities in their replicative proteins and are thought to have evolved from a common ancestor.

Animals

Prevention of sepsis following endoscopic retrograde cholangiopancreatography.

Ora; ciprofloxacin was studied as a prophylactic antimicrobial agent in high- and low-risk patients undergoing endoscopic retrograde cholangiography. Ciprofloxacin appeared to be effective, good serum levels were attained, and the drug compared favourably on grounds of cost and convenience with a parenterally-administered cephalosporin.

Administration, Oral

Health, stress, psychological resources, and subjective well-being among older blacks.

This study examines the structural relationships among sociodemographic characteristics, health status, stress, psychological resources, and subjective well-being (SWB) among the Black elderly. A structural equation model of SWB was evaluated with data from the 1979-1980 National Survey of Black Americans. The results revealed that poor subjective health status was predictive of lower levels of personal efficacy and SWB. Stressful life events tended to depress subjective assessments of health and had negative effects on self-esteem and SWB. Marital status and age had positive effects on SWB. Chronic health conditions and other demographic variables, however, had indirect effects on SWB.

Adaptation, Psychological

Isolation and characterization of PEP3, a gene required for vacuolar biogenesis in Saccharomyces cerevisiae.

The Saccharomyces cerevisiae PEP3 gene was cloned from a wild-type genomic library by complementation of the carboxypeptidase Y deficiency in a pep3-12 strain. Subclone complementation results localized the PEP3 gene to a 3.8-kb DNA fragment. The DNA sequence of the fragment was determined; a 2,754-bp open reading frame predicts that the PEP3 gene product is a hydrophilic, 107-kDa protein that has no significant similarity to any known protein. The PEP3 predicted protein has a zinc finger (CX2CX13CX2C) near its C terminus that has spacing and slight sequence similarity to the adenovirus E1a zinc finger. A radiolabeled PEP3 DNA probe hybridized to an RNA transcript of 3.1 kb in extracts of log-phase and diauxic lag-phase cells. Cells bearing pep3 deletion/disruption alleles were viable, had decreased levels of protease A, protease B, and carboxypeptidase Y antigens, had decreased repressible alkaline phosphatase activity, and contained very few normal vacuolelike organelles by fluorescence microscopy and electron microscopy but had an abundance of extremely small vesicles that stained with carboxyfluorescein diacetate, were severely inhibited for growth at 37 degrees C, and were incapable of sporulating (as homozygotes). Fractionation of cells expressing a bifunctional PEP3::SUC2 fusion protein indicated that the PEP3 gene product is present at low abundance in both log-phase and stationary cells and is a vacuolar peripheral membrane protein. Sequence identity established that PEP3 and VPS18 (J. S. Robinson, T. R. Graham, and S. D. Emr, Mol. Cell. Biol. 11:5813-5824, 1991) are the same gene.

Adaptor Proteins, Vesicular Transport

Deoxyribonucleic acid amplification and hybridisation in Crohn's disease using a chlamydial plasmid probe.

The possibility that Crohn's disease is caused by infection with Chlamydia trachomatis was examined by probing for chlamydial plasmid deoxyribonucleic acid (DNA) in DNA extracts from Crohn's disease tissue and by means of a serological study. Gut DNA extracts were obtained from 10 patients with Crohn's disease and four control subjects and were probed with a chlamydial plasmid probe after Southern blotting. The polymerase chain reaction was also used to amplify any chlamydial plasmid DNA present in tissue DNA extracts, before Southern blotting and probing. Chlamydial proctitis control specimens were not available: gut DNA extracts mixed with traces of chlamydia plasmid served as positive controls. Using these techniques, no chlamydial plasmid DNA sequences were found in Crohn's disease tissue. An enzyme linked immunosorbent assay for C trachomatis LI was performed on 48 patients with Crohn's disease and 48 control subjects. Seropositivity was present in 14.6% of patients and 29% of control subjects and was not statistically significant (p greater than 0.05). The failure to show chlamydial DNA and the lack of serological response to chlamydia make C trachomatis infection a very unlikely factor in the pathogenesis of Crohn's disease.

Adult

Adult age and the rate of an internal clock.

Two experiments were conducted to determine whether young and old adults differ in the rate of a hypothetical internal clock. Clock rate was measured as the slope of the function relating actual duration to perceived duration. No age differences were apparent when subjects were asked to judge the duration of a flash of light in Exp. I, or to judge the duration of a dark interval between two light flashes in Exp. II. It was concluded that there is no evidence to support the hypothesis that perceptual and motor speed differences associated with increased age can be attributable to a slower rate of internal time.

Adolescent

Serum lysozyme levels in malignant histiocytosis of the intestine.

Serum lysozyme levels were significantly raised in a group of eight patients with malabsorption associated with gastrointestinal lymphomas of a type recently characterised as malignant histiocytosis of the intestine. In four of the cases, levels were markedly raised. In contrast there was no significant difference between groups of patients with uncomplicated adult coeliac disease and healthy controls. The estimation of serum lysozyme is a simple test to perform and may be valuable in the diagnosis of malignant histiocytosis of the intestine, in particular differentiating it from uncomplicated adult coeliac disease.

Adolescent

Antibodies to maize in patients with Crohn's disease, ulcerative colitis and coeliac disease.

The incidence of antibodies to maize using an immunofluorescent technique has been found to be 14% in controls, 33% in Crohn's disease, 50% in ulcerative colitis and 44% in coeliac disease. This result indicates that humoral immunity to maize is probably unimportant in the pathogenesis of Crohn's disease. The similar incidence of antibodies in the inflammatory bowel disease and coeliac groups suggests absorption of dietary antigen secondary to an increased mucosal permeability.

Antibodies