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Biomedical subjects

M McGrath

Publications and source records attributed to M McGrath.

At least 19 recordsLinked to original sources
PubMed1996

Effects of dietary n-3 fatty acid supplementation in men with weight loss associated with the acquired immune deficiency syndrome: Relation to indices of cytokine production.

Cytokines may be involved in weight loss and disturbances of metabolism associated with human immunodeficiency virus (HIV) infection. Dietary n-3 fatty acids reduce the production of interleukin-1 (IL-1) and tumor necrosis factor (TNF) by peripheral blood mononuclear cells (PBMC) in normal humans and prevent IL-1 and TNF anorexia in animals. Accordingly, we studied the nutritional and metabolic effects of a 10-week trial of dietary fish oil (MaxEPA 18 g/day) in men with weight loss due to acquired immune deficiency syndrome (AIDS). Twenty men were enrolled, and 16 completed the 10-week supplementation period. Prior weight loss was 13.7 +/- 1.8 kg(17.4 +/- 1.6% body weight, means +/- SE). Food intake, body composition, blood chemistries, serum cytokine concentrations, in vitro production of IL-1 and TNF by PBMC, and clinical course were followed. A subset of subjects (n=12) underwent stable isotope infusions to measure de novo hepatic lipogenesis (DNL), an in vivo metabolic index that is influenced by cytokine presence and has previously been found to be elevated in AIDS. An unsupplemented group of men with AIDS wasting (10.4 +/- 2.4 kg weight loss, 13.1 +/- 2.2% body weight) was monitored for 10 weeks as controls. Baseline food intake (2,395 +/- 177 kcal/day and 95.1 +/- 7.2 g protein/day), body weight, percent fat, and fat-free mass were unchanged over the 10-week supplementation period. Serum triglycerides were reduced in hypertriglyceridemic subjects, confirming compliance with fish oil supplementation and suggesting that their hypertriglyceridemia was at least in part due to overproduction. Serum TNF and IL-1 were undetectable before or after fish oil supplementation. Serum interferon alpha (IFN) was measurable but did not change. In vitro production of IL-1 and TNF by PBMC was markedly reduced both at baseline and after fish oil supplementation in this population, even in the presence of new AIDS complications, compared with normal controls. The metabolic measurement DNL fell and weight was gained (2.1 +/- 1.3 kg) in subjects who did not develop new AIDS-related complications, but further increases in DNL and further weight loss were observed in subjects who developed a new AIDS complication (p<0.05 for interaction between new complication and change in DNL). No changes in body weight, food intake, serum triglycerides, serum cytokines, or DNL were observed in the unsupplemented group. We conclude that fish oil is a weak anticytokine agent that is unable to overcome the metabolic and nutritional consequences of acute AIDS-related complications but may exert a clinical anticytokine effect in stable AIDS patients. Cytokine production by PBMC is not a useful or reliable marker of in vivo cytokine activity in AIDS patients with weight loss. In contrast, an integrative functional index that is sensitive to cytokine presence in tissues (hepatic DNL) correlated with clinical response. These findings are relevant to the design of future studies of more potent anticytokine agents, such as thalidomide.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Lytic growth of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in culture.

Kaposi's sarcoma (KS) is the leading neoplasm of AIDS patients, and HIV infection is known to be a major risk factor for its development. However, KS can occur in the absence of HIV infection and the risk of KS development varies widely even among HIV-infected patients, with homosexual men with AIDS being 20 times more likely to develop KS than AIDS-afflicted children or hemophiliacs. These and other data strongly suggest that a sexually transmitted agent or co-factor may be involved in KS pathogenesis. Recently, DNA sequences corresponding to the genome of a novel member of the herpesvirus family have been identified within AIDS-KS biopsies, and several reports indicate that these sequences are also present in all forms of HIV-negative KS. These and other findings suggest this new agent, referred to as KS-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8), as a candidate for the putative etiologic cofactor. However, the role of this agent in KS remains hotly debated. Further progress in understanding its biology has been severely hampered by the lack of a cell culture system for virus growth. Here we report the development of a system for the lytic growth of this virus in a latently infected B cell line and present the first ultrastructural visualization of the virus. This system will facilitate the detailed study of the molecular biology of viral replication, the testing of antiviral drugs and the development of diagnostic tests for viral infection.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Role of the cytoskeleton in the reaction of fibroblasts to multiple grooved substrata.

The role of the cytoskeleton and cell attachments in the alignment of baby hamster kidney fibroblasts to ridge and groove substratum topography was investigated using confocal scanning microscopy. This was carried out with normal cells and cells treated with the cytoskeleton modifiers cytochalasin D, colcemid, and taxol. Actin was localised with fluorescent phalloidin. Tubulin, vinculin, and intracellular adhesion molecule-1 were visualised by indirect immunofluorescence. The spreading, elongation, and orientation of the cells after 24 h of culture in these conditions were measured on grooves of 5, 10, and 25 microns width and 0.5, 1, 2, and 5 microns depth. We have also observed events over the first 30 min of cell attachment. Five minutes after cell attachment, F-actin condensations were seen close to the intersection of groove wall and ridge top, that is, at a topographic discontinuity. The condensations were often at right angles to the groove edge and showed a periodicity of 0.6 microns. Vinculin arrangement at the early stages of cell spreading was similar to that of actin. Organisation of the microtubule system followed later, becoming obvious at about 30 min after cell plating. The Curtis and Clark theory (that cells react to topography primarily at lines of discontinuity in the substratum by actin nucleation) is supported by these results. The use of cytoskeletal poisons did not entirely abolish cell reaction to grooves. Colcemid increased cell spreading and reduced cell orientation and elongation. Cytochalasin D reduced cell spreading, orientation, and elongation. Taxol reduced cell elongation but did not affect cell spreading and orientation. We conclude that the aggregation of actin along groove/ridge boundaries is a primary driving event in determining fibroblast orientation on microgrooved substrata.

Animals↗
PubMed1995

Mastery motivation and cognitive development in 4-year-old children born at various degrees of medical risk.

Although technology has enabled premature infants to survive, longitudinal assessments have primarily focused on IQ outcomes. The purpose of this study was to establish the usefulness of mastery assessment in establishing developmental outcome. Mastery motivation and cognition were examined in 167 preschool children born at various degrees of medical risk. Mastery motivation was measured by a videotaped toy sequence designed to tap sensorimotor practice, effect production, and problem solving. Patterns of correlations indicate that the relationship between mastery and IQ were complementary and not redundant. Three regression models showed that significant interactions between perinatal status and mastery motivation behaviors confirm mastery assessment worthy of consideration in biologically high-risk children.

Achievement↗
PubMed1995

Early clinical experience with a hybrid bioartificial liver.

BACKGROUND: Severe liver failure is associated with high mortality. Orthotopic liver transplantation (OLT) is the only effective therapeutic modality; there is a need for a 'bridge' system to support patients until an organ becomes available. METHODS: A bioartificial liver (BAL) was used to treat 10 patients with severe liver failure. A plasmapheresis system was used to pump patient plasma through a module with porcine hepatocytes. Each treatment lasted 6-7 h. RESULTS: All patients tolerated the procedure(s) well. Eight patients underwent OLT following BAL treatment(s). There were two late deaths after recovery from liver failure. Five patients with increased intracranial pressure (ICP) and decerebration had ICP normalization, increased cerebral perfusion pressure and full neurologic recovery after OLT. There was improvement in the level of encephalopathy and a significant decrease in serum ammonia after BAL treatment(s). CONCLUSIONS: BAL treatment is safe and beneficial and can be successfully used as a 'bridge' to transplantation.

Adult↗
PubMed1994

A bioartificial liver to treat severe acute liver failure.

OBJECTIVE: To test the safety and efficacy of a bioartificial liver support system in patients with severe acute liver failure. SUMMARY BACKGROUND DATA: The authors developed a bioartificial liver using porcine hepatocytes. The system was tested in vitro and shown to have differentiated liver functions (cytochrome P450 activity, synthesis of liver-specific proteins, bilirubin synthesis, and conjugation). When tested in vivo in experimental animals with liver failure, it gave substantial metabolic and hemodynamic support. METHODS: Seven patients with severe acute liver failure received a double lumen catheter in the saphenous vein; blood was removed, plasma was separated and perfused through a cartridge containing 4 to 6 x 10(9) porcine hepatocytes, and plasma and blood cells were reconstituted and reinfused. Each treatment lasted 6 to 7 hours. RESULTS: All patients tolerated the procedure(s) well, with neurologic improvement, decreased intracranial pressure (23.0 +/- 2.3 to 7.8 +/- 1.7 mm Hg; p < 0.005) associated with an increase in cerebral perfusion pressure, decreased plasma ammonia (163.3 +/- 21.3 to 112.2 +/- 9.8 microMoles/L; p < 0.01), and increased encephalopathy index (0.60 +/- 0.17 to 1.24 +/- 0.22; p < 0.03). All patients survived, had a liver transplant, and were discharged from the hospital. CONCLUSIONS: This bioartificial liver is safe and serves as an effective "bridge" to liver transplant in some patients.

Adolescent↗
PubMed1993

Breaking the adhesions of a cell with its substratum.

Investigation of the relative slowness with which trypsin detaches epithelial cells from their adhesions with a substratum suggests that the adherent surface of the cells is normally rather inaccessible to the enzyme. Trypsinisation of cells through a porous filter allowing access of the enzyme to the underside of the cells greatly accelerated detachment: a result consistent with this explanation.

Animals↗
PubMed1993

A non-lymphoma idiotype is indicative and predictive for B cell malignancies in AIDS.

The 1F7 idiotype previously defined (J Immunol 147:933;1991 and Eur J Immunol 22:1749;1992) is expressed on antibodies reactive to different proteins of HIV (gp41, p24, gp120). Since serum levels of 1F7 (IgM or IgG) are significantly higher in patients with HIV lymphoma as opposed to HIV-infected individuals, normal controls and non-HIV lymphoma patients, we hypothesized the B-cell neoplasms were the source of the idiotype. However, immunohistochemistry on cryostat sections revealed no 1F7 idiotype signal on neoplastic B-cells nor tumor infiltrative T-cells (n = 8). Interestingly, reactive lymphocytosis adjacent to tumor masses and reactive follicular hyperplastic controls (n = 5) exhibited significant 1F7 reactivity. The reactivity appeared in paracortical and perifollicular lymphoid regions, predominantly regions of B, T and antigen presenting cells in lymph nodes or tonsils. A survey of electrophoretically defined paraproteins with anti-HIV specificities derived from HIV-infected patients showed no Western blot reactivity with the 1F7 anti-idiotypic antibody. Therefore, the idiotype does not appear to be a direct product of B-cell neoplasia or abnormal B-cell proliferation, but is produced by B cell clones responding to HIV infection. This high level of serum 1F7 reactivity could be an important clue in the pathogenesis of HIV lymphomas and confers a highly predictive serological test for HIV lymphoma.

Animals↗
PubMed1993

Nailfold capillary circulation in osteoarthritis.

Nailfold capillaries in 28 patients with OA affecting the distal interphalangeal joints were compared to 23 age- and sex-matched controls without OA. Patients with OA showed a significantly lower density of capillaries in their nailfolds and significantly more capillary morphological abnormalities including haemorrhage, 'drop out', dilatation and irregularity. There was a trend for OA patients to have warmer fingers with reduced finger to brachial blood pressure ratios. There were significant correlations between nailfold capillary numbers and average joint tenderness and between capillary morphological changes and joint swelling. These results reveal a relationship between interphalangeal joint OA and nailfold capillary abnormalities and density. As changes in microcirculation may be pertinent to the pathogenesis of OA, further studies which could explore possible causal relationships are warranted.

Aged↗
PubMed1992

Appropriateness of the Draw-A-Person test with Alaskan Native populations.

The appropriateness of the Draw-A-Person test with Alaskan Native populations was assessed by matching 33 White subjects to 33 Alaskan Native subjects, asking them to perform the DAP, and rating their performance according to eight criteria chosen for their clinical relevancy. Results indicated that neither level of commitment to Native culture nor ethnicity per se affected drawing ratings. It is hypothesized that the DAP is a useful clinical tool appropriate for use with Alaskan Native populations.

Acculturation↗
PubMed1992

Molecular and immunophenotypic characterization of AIDS-associated, Epstein-Barr virus-negative, polyclonal lymphoma.

PURPOSE: A molecular analysis of non-Hodgkin's lymphomas (NHLs) from patients with AIDS was undertaken to determine the prevalence and immunophenotype of polyclonal B-cell lymphoma. MATERIALS AND METHODS: DNA was extracted from 40 diagnostic biopsy specimens obtained from patients seen at University of California, San Francisco (UCSF) between 1986 and 1990. Clonality, infection with Epstein-Barr virus (EBV), and presence of a rearranged c-myc gene were determined by Southern blot analysis. Lymphoma immunophenotypes were determined by frozen-section immunohistochemical analysis. RESULTS: The most prevalent genotype of lymphoma in this study was that of polyclonal, EBV-negative tumors with no evidence of c-myc rearrangement (14 of 40; 35%). Monoclonal, EBV-positive tumors with no evidence of c-myc rearrangement comprised the second most prevalent class (10 of 40; 25%), and polyclonal, EBV-positive tumors similar to those seen in transplant patients were observed in only a small subset (three of 40; 8%) of specimens analyzed. The immunophenotype of B cells in the polyclonal EBV-negative subset was equally divided into B-cell-predominant and mixed-phenotype lymphomas, with the latter category containing numerous infiltrating T cells. The B cells in each category were immunoglobulin M-positive (IgM+), CD20+, CD21-. All but one of the polyclonal NHLs had large-cell histology. CONCLUSIONS: EBV-negative, AIDS-associated, polyclonal B-cell lymphoma appears to be a new class of human immunodeficiency virus (HIV)-associated disease more prevalent in the current study than any other molecular subclass. The absence of CD21, the EBV receptor, may explain in part the absence of EBV within this polyclonal B-cell population.

Blotting, Southern↗
PubMed1992

Localised application of an activating signal to a cell: experimental use of fibronectin bound to beads and the implications for mechanisms of adhesion.

Small beads derivatised with fibronectin or with bovine serum albumin are allowed to attach to BHK cells in suspension at low ratios of beads to cells. In this way populations of cells bearing predominantly one bead per cell can be prepared. We show that the attachment of one bead per cell affects the adhesion and spreading of that cell on substrata, raising adhesion and increasing spreading if the signal molecule is fibronectin, decreasing these quantities if the bead bears BSA. The experiments are conducted in the absence of other sources of exogenous fibronectin and in some cases in the additional absence of endogenous sources. The effects are especially marked if the substratum is adsorbed haemoglobin on which control cells show little attachment or spreading. We further show by interference reflection microscopy and by scanning electron microscopy that the beads are found on the non-adhering side (uppermost or outer) of the cell when fibronectin-bearing beads are used, presumably because fibronectin will not attach to haemoglobin. The increased adhesion and spreading found in such cases must be attributed to an activation produced by the bead, which spreads to other parts of the cell and which activates a fibronectin-independent mode of adhesion.

Animals↗
PubMed1991

A turnover prevention program for child care workers: a failed effort?

This study describes efforts to reduce turnover of child care workers, one of the many activities undertaken within the Milieu Enhancement Project. This 3-year endeavor, funded by the Division of Nursing of the Department of Health and Human Services, allowed nurses to provide care for orphaned and disadvantaged children, test the value of a nursing practice model, analyze the cost-benefit and the cost-effectiveness of the project, computerize existing and model-derived health care records, and allow faculty and graduate students to practice autonomously in a nontraditional setting. The research question was: What is causing job dissatisfaction in child care workers? Nurses and social workers used the Milieu Enhancement Model to conceptualize, address, and evaluate factors contributing to turnover. While statistical significance was not obtained in the turnover rates before and after implementation of the Turnover Prevention Program, the milieu was enhanced in many ways. Data are presented to support many aspects of the program's success.

Adult↗
PubMed1991

Human T cell lymphotropic virus types I and II in intravenous drug users in San Francisco: risk factors associated with seropositivity.

Serologic assays for human T cell lymphotropic virus types I and II (HTLV I/II) infection were done in 676 intravenous drug users (IVDUs) in San Francisco between 1985 and 1987: 150 in 1985, 44 in 1986, and 482 in 1987. All sera were tested by Western blot, ELISA, and p24 RIA. A total of 111 participants were seropositive in a minimum of two assays. Duration of intravenous heroin use was strongly associated with the risk of HTLV I/II seropositivity: greater than or equal to 21 years odds ratio, 6.1 (95% confidence interval [CI], 2.2-17.5), compared with less than 10 years of heroin use. Additional independent risk factors included black or Hispanic race, female sex, and the use of drugs in a shooting gallery. Coinfection of HTLV I/II and human immunodeficiency virus was less frequent than expected by chance (P less than .02). Longitudinal specimens were available in 154 participants. The age- and race-adjusted seroconversion rate was 3.4% (95% CI, 1.3-8.9) per person per year. Of the 349 homosexual men tested, none were HTLV I/II-seropositive.

Adult↗