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Biomedical subjects

L Powell

Publications and source records attributed to L Powell.

At least 19 recordsLinked to original sources
PubMed1992

Improved diagnosis of chronic hepatitis C virus infection by detection of antibody to multiple epitopes: confirmation by antibody to synthetic oligopeptides.

Serum samples from 226 patients covering a wide spectrum of liver disease were tested for antibodies to hepatitis C virus (HCV) using both first and second generation enzyme linked immunosorbent assays. Selected sera were also tested by peptide immunoassays, by the four-antigen recombinant immunoblot assay (RIBA II), and for viral genome by the polymerase chain reaction. Antibody to c100-3 was detected in 61% of patients with chronic non-A, non-B (NANB) hepatitis and/or 46.5% with presumed NANB-related cirrhosis by the first generation test. These figures increased to 77% and 58% when antibodies to recombinant structural and non-structural HCV antigens were sought by the second generation assay. Supplemental testing against peptide Sp75 and Sp65/sp67 confirmed that reactivity of sera by second generation assays was due to antibodies to the additional structural and non-structural antigens. Samples negative by the first generation assay were not confirmed by the supplemental assay using peptides Sp75 and Sp65/Sp67. HCV RNA was detected in 60% of the anti-HCV positive sera tested, most of which were also RIBA II positive. Our findings confirm that the introduction of the structural and non-structural antigens, especially the putative nucleocapsid protein, improves sensitivity of detection of antibodies to HCV, and facilitates diagnosis in patients with "cryptogenic" chronic hepatitis.

Antigens, Viral↗
PubMed1992

Physical and genetic mapping of the telomeric major histocompatibility complex region in man and relevance to the primary hemochromatosis gene (HFE).

We performed pulsed-field gel electrophoresis (PFGE) on genomic DNA from a radiation hybrid (RH) cell line and constructed a high-resolution physical map of the major histocompatibility complex class I region in 6p21.3, where the gene for primary hemochromatosis (HFE) is believed to be located. Due to the intact microsegment of hemizygous human genomic DNA preserved in the RH cell line, simplified and distinct restriction fragment banding patterns were generated. Using the RH cell line, we were able to extend the physical map of the HLA class I region to about 3000 kb, order the known HLA class I genes from centromere to telomere: HLA-B, -C, -E, (-A, -H, -G), and -F, and orient the HLA-F gene along the chromosome. The proximity of HLA-F to HLA-A was confirmed by linkage and linkage disequilibrium analysis. This study shows that RH cell lines can be useful for constructing long-range physical maps in specific regions of the human genome with PFGE. Physical and genetic mapping studies of this region are consistent with a localization of the HFE gene proximal or distal to HLA-A.

Animals↗
PubMed1991

Polymorphism in a ferritin H gene from chromosome 6p.

This paper addresses the question of whether abnormalities in ferritin expression in the iron storage disease hemochromatosis (HC) involve major deletions or alterations in regions containing the two ferritin H genes that lie near the disease locus on chromosome 6p. We present evidence from analyses of Southern blots that neither gene is deleted in hemochromatosis. We also describe a polymorphism in one of the genes that we have previously shown to be a processed pseudogene. This polymorphism does not correlate with the presence of HC. The PIC value for this polymorphism was calculated as 0.49.

Blotting, Southern↗
PubMed1990

Anesthetic considerations for gynecologic cancer surgery.

Preoperative, intraoperative, and postoperative anesthetic considerations in gynecologic cancer surgery are discussed. Preoperatively, the anesthetist must document the patient's disease state, physical condition, responses to prior chemotherapeutic regimens and toxic side effects, particularly from Adriamycin and bleomycin. Laboratory studies should include electrolytes, hepatic, renal, and hematologic indices. The anesthetist should also recognize that patients may be under great emotional stress, which may require prescribing anti-anxiety medications for several days prior to surgery. Planning the anesthetic includes consultation with the surgeon relative to procedure planned, positioning requirements, anticipated blood loss, monitoring and postoperative care requirements. Intraoperative considerations again involve close communication with the surgeon. The use and benefits of a combined regional/general anesthetic technique are discussed. Postoperative considerations are directed toward hemodynamic stability and control of postoperative pain. Techniques of epidural narcotic and local anesthetic administration, as well as patient-controlled analgesia (PCA) are discussed.

Anesthesia, Conduction↗
PubMed1990

Internal deletions in the yeast transcriptional activator HAP1 have opposite effects at two sequence elements.

In this report we study the effects of internal deletions of the yeast transcriptional activator HAP1 (CYP1) on activity at two dissimilar DNA binding sites, upstream activation sequence 1 (UAS1) of CYC1 (iso-1-cytochrome c) and CYC7 (iso-2-cytochrome c). These deletions remove up to 1061 amino acids of the 1483-residue protein and bring the carboxyl-terminal acidic activation domain closer to the amino-terminal DNA-binding domain. Surprisingly, the deletions have opposite effects at the two sites; activity at UAS1 increases with deletion size, while activity at CYC7 decreases. The mutant with the largest deletion, mini-HAP1, has no measurable activity at CYC7 but binds normally to the site in vitro. In contrast, a protein with the DNA-binding domain of HAP1 fused to the acidic activation domain of GAL4 is active at both UAS1 and CYC7. These findings are discussed in the context of two models that suggest how the DNA sequence can alter the activity of the bound HAP1. In a separate experiment, we generate a mutation in the DNA-binding domain of HAP1 that requires the addition of zinc for binding to either UAS1 or CYC7 in vitro. This finding shows that a zinc finger anchors DNA binding to both types of HAP1 sites.

Chromosome Deletion↗
PubMed1990

Internuclear exchange of an inner nuclear membrane protein (p55) in heterokaryons: in vivo evidence for the interaction of p55 with the nuclear lamina.

The movement between nuclei of an integral protein of the inner nuclear membrane has been studied in rat/mouse and rat/hamster heterokaryons. This protein, p55, was found to equilibrate between nuclei over a period of approximately 6 h in the absence of new protein synthesis. When rat/mouse heterokaryons were constructed using an undifferentiated murine embryonal carcinoma (P19), which lacks lamins A and C, no accumulation of p55 in the mouse cell nucleus was observed. However, P19 nuclei could be rendered competent to accumulate p55 by transfecting the parent cells with human lamin A before cell fusion, supporting the notion that p55 may interact with the nuclear lamina. Since p55 does not appear to be able to dissociate from the nuclear membrane, it is concluded that this exchange between nuclei does not occur in the aqueous phase and instead is probably membrane mediated. It is proposed that this protein may be free to move between the inner and outer nuclear membranes via the continuities at the nuclear pore complexes and that transfer between nuclei occurs via lateral diffusion through the peripheral ER, which appears to form a single continuous membrane system in these heterokaryons. One implication of these observations is that accumulation of at least some integral proteins in the inner nuclear membrane may be mediated by interactions with other nuclear components and may not require a single defined targeting sequence.

Animals↗
PubMed1990

Falls efficacy as a measure of fear of falling.

We developed the Falls Efficacy Scale (FES), an instrument to measure fear of falling, based on the operational definition of this fear as "low perceived self-efficacy at avoiding falls during essential, nonhazardous activities of daily living." The reliability and validity of the FES were assessed in two samples of community-living elderly persons. The FES showed good test-retest reliability (Pearson's correlation 0.71). Subjects who reported avoiding activities because of fear of falling had higher FES scores, representing lower self-efficacy or confidence, than subjects not reporting fear of falling. The independent predictors of FES score were usual walking pace (a measure of physical ability), anxiety, and depression. The FES appears to be a reliable and valid method for measuring fear of falling. This instrument may be useful in assessing the independent contribution of fear of falling to functional decline among elderly people.

Accidental Falls↗
PubMed1988

Apolipoprotein B: a novel mechanism for deriving two proteins from one gene.

Evidence from antibody and peptide mapping, protein sequencing and amino acid composition studies suggests that intestinal apo-B48 is colinear with the amino terminal half of hepatic apo-B100. To investigate the mechanism of apo-B48 production we examined cDNA clones from human and rabbit small intestine. All clones contained a single C----T base difference from the hepatic sequence resulting in a translational stop at codon 2153. Amplification by the polymerase chain reaction of cDNA from human and rabbit small intestine, rabbit liver and the human hepatoma cell line HepG2 showed that the stop codon was only present in intestinal mRNA. Enterocyte genomic DNA did not contain the stop codon. We suggest that a co- or post-transcriptional C----U change may result in the production of apo-B48, which represents the amino terminal 2152 amino acids of apo-B100. This is the first example of tissue specific modification of a single mRNA nucleotide resulting in two different proteins from the same primary transcript.

Animals↗
PubMed1987

The Queensland Liver Transplant Programme: the first two years.

Orthotopic liver transplantation began in Brisbane in January 1985. During the first two years of the programme an assessment committee evaluated 55 patients (38 adults, 17 children). Patients were either accepted for transplantation, rejected as unsuitable or deferred for elective reassessment. All of the 10 adults who were rejected for transplantation because they had "too advanced" disease died within four months of assessment. Six children who were accepted for transplantation died before a suitable donor liver could be found. In the first two years, 21 orthotopic liver transplantations were performed on 18 patients (adults, 13 patients; children, five patients). Fifteen of 21 grafts were procured from within Queensland. Twelve (67%) patients are alive at three to 23 months and all have been discharged from hospital. Deaths in adults were due to sepsis (three patients), aspiration pneumonitis (one patient), rejection and hepatic artery thrombosis (one patient) and the recurrence of a hepatocellular carcinoma five months after discharge from hospital (one patient). Two patients underwent a second transplantation procedure because of chronic rejection at four months and at 11 months, respectively, after the initial operation. One patient received a second transplant for primary graft failure at four days after the operation. A scoring system which considered the presence of pre-operative patient factors, such as coma, ascites, malnutrition and previous abdominal surgery, partly predicted the operative blood loss and patient survival. In conclusion, orthotopic liver transplantation is being performed in Australia with survival rates that are comparable with those of established overseas units.

Adolescent↗
PubMed1986

Structure of the human apolipoprotein B gene.

Human apolipoprotein B100 cDNA is 14 kilobases in length and encodes a 4563-amino acid precursor protein. The corresponding human gene has been isolated as a series of overlapping lambda clones and extends over 43 kilobases. The gene comprises 29 exons and 28 introns. The distribution of introns is extremely asymmetrical, most of them appearing in the 5'-terminal one-third of the gene. Although most of the exons fall within the normal size limits for mammalian genes, two are unusually long: 1906 and 7572 base pairs. The latter exon is by far the longest reported for a vertebrate gene.

Apolipoproteins B↗