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Biomedical subjects

J A Metcalf

Publications and source records attributed to J A Metcalf.

11 recordsLinked to original sources
PubMed1992

Indeterminate western blot patterns in a cohort of individuals at high risk for human immunodeficiency virus (HIV-1) exposure.

Our objective was to map serial patterns of Western blot reactivity over time of a cohort of initially ELISA-negative, Western blot-indeterminate individuals from a high-risk group and to determine if these individuals were at increased risk of harboring occult HIV-1 infection. A 2-year prospective study used serial ELISA, two types of Western blot, immunologic profiles, HIV-1 culture, and analysis by polymerase chain reaction. Subjects were 20 ELISA-negative, Western blot indeterminate homosexual volunteers and 20 matched seronegative controls. Results showed that 19 of 20 study subjects completed a mean of 17.0 months of clinical and laboratory follow-up. Reactivities with p24 and/or with p55 were the two most commonly observed Western blot patterns, occurring in 70% of individuals. Specific Western blot reactivity was dependent upon the particular immunoblot preparation being used and varied considerably on a longitudinal basis. No individual pattern appeared predictive of an increased likelihood of subsequent seroconversion to HIV-1 relative to controls. By all other criteria including polymerase chain reaction analysis, samples from 17 of 19 individuals remained negative for HIV-1 at each time point. Two individuals evolved from an indeterminate to a positive Western blot and, simultaneously, from a negative to a positive polymerase chain reaction analysis, during follow-up. Our conclusions were as follows. ELISA-negative, Western blot-indeterminate individuals from a high-risk group show marked variability in immunoblot findings over time, and these patterns do not appear predictive of an increased likelihood of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Variations in blood flow to and from the bovine mammary gland measured using transit time ultrasound and dye dilution.

Blood flow across the lactating bovine mammary gland was measured by two techniques. The use of transit time flow probes appeared to give flows which correlated well with dye dilution in only one of five cows, although the relative changes in flow were similar between the techniques in four of the cows. Further studies were made on the effect of posture on mammary blood flow using both techniques. The crossover of venous blood from one side of the mammary gland was also studied using the dye dilution technique, and revealed large differences between animals and also with posture. These observations suggest that particular care should be taken when sampling blood from the milk vein of cows, if a representative sample is required. Changes in blood flow with posture may be indicative of a repartitioning of flow within the body, and the physiology of such a mechanism would be of interest in itself. The control of this mechanism may be useful in modifying blood flow to the mammary gland and thus milk yield, since blood flow is related to the level of milk production.

Animals↗
PubMed1992

Isolation of HIV-1 from plasma of infected individuals: an analysis of experimental conditions affecting successful virus propagation.

Experimental conditions affecting the successful propagation of HIV-1 from the plasma of seropositive individuals were examined. It was determined that whole blood samples collected with lithium heparin as the anticoagulant, immediate plasma separation, and immediate culturing were best suited for obtaining viable virus from plasma. Virus was isolated by infecting fresh phytohemagglutinin-stimulated normal donor peripheral blood mononuclear cells (PBMCs) with plasma followed by weekly cocultivation with new target cells. The plasma virus isolation rate was the greatest and HIV-1 titers were the highest for those individuals with less than 200 CD4+ cells/mm3 and decreased as the level of CD4+ cells approached normal values. We were able to obtain positive cultures from 29.5% of those patients with CD4+ counts greater than 500/mm3. HIV-1 titers in plasma also correlated with high serum p24 antigen levels when serum was treated with glycine to dissociate antigen-antibody complexes.

Adult↗
PubMed1991

Insulin binding to skeletal muscle microsomes in lactating and dry sheep.

Microsomes were prepared from skeletal muscles taken from lactating and non lactating ewes. Insulin binding to these microsomes was not affected by reproductive status. There were significant differences in the ability of individual muscles to bind insulin. These differences correlated with the function of the muscle, as defined by the predominant muscle fibre type.

5'-Nucleotidase↗
PubMed1991

A phase I/II trial of zidovudine, interferon-alpha, and granulocyte-macrophage colony-stimulating factor in the treatment of human immunodeficiency virus type 1 infection.

Twenty-four patients infected with human immunodeficiency virus type 1 (HIV-1) who had CD4+ counts of 0.2-0.5 x 10(9) cells/l received granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with zidovudine plus escalating doses of daily subcutaneous interferon-alpha. Mean neutropenia-inducing doses of interferon-alpha were 9.4 x 10(6) and 10.6 x 10(6) IU/day for groups receiving 100 or 200 mg zidovudine every 4 h, respectively. Mean GM-CSF doses used to reverse neutropenia were 0.64 and 0.63 microgram/kg/day for these two groups, respectively, although the mean minimum effective GM-CSF dose for both was only 0.30 microgram/kg/day. Serum p24 antigen declined greater than 70% in all 5 antigenemic patients. Toxicities included a dose-dependent increase in lymphokine-like side effects (100%), anorexia and weight loss (42%), fatigue (42%), and anemia (50%). While toxicities of the combination can be significant, low-dose GM-CSF readily ameliorated neutropenia associated with zidovudine and interferon-alpha therapy without adversely affecting the antiviral properties of the combination.

Administration, Oral↗
PubMed1991

The influence of insulin and amino acid supply on amino acid uptake by the lactating bovine mammary gland.

Four lactating dairy cows received arterial infusions of insulin (1.41 U/h), an AA mixture (threonine, methionine, leucine, phenylalanine, and lysine at 5.87, 1.90, 3.55, 2.17, and 4.21 mmol/h, respectively), and a combination of the two in a 4 x 4 Latin square. The infusions were performed over a 3-d period directly into the extra pudic artery on both sides of the mammary gland, and samples were taken simultaneously of the downstream extra pudic arterial blood and also of subcutaneous abdominal venous blood. Blood flow was measured by dye dilution using p-amino-hippuric acid and was increased by 37% by infusion of insulin plus AA (P less than .05). Infusions of AA tended to increase the arteriovenous difference and uptake of the infused AA (P less than .05 for phenylalanine) and had varying effects on the uninfused AA. Inclusion of insulin in the AA infusion tended to increase uptake of infused AA, whereas infusions of insulin alone tended to decrease uptake. There were no significant effects of infusion on milk yield or composition.

Amino Acids↗
PubMed1990

Interferon-alpha in patients with asymptomatic human immunodeficiency virus (HIV) infection. A randomized, placebo-controlled trial.

STUDY OBJECTIVE: To evaluate the toxicity and clinical efficacy of interferon-alpha 2b (IFN-alpha) in patients with asymptomatic human immunodeficiency virus (HIV) infection. DESIGN: Randomized, placebo-controlled, and double-blind study. SETTING: Outpatient clinic of a government referral-based research hospital. PATIENTS: Volunteer sample of 34 patients with asymptomatic HIV infection who had CD4 counts of 400 cells/mm3 or more, positive peripheral blood mononuclear cell cultures for HIV, or p24 antigenemia. INTERVENTIONS: Patients were randomly assigned to receive either IFN-alpha or placebo, 35 x 10(6) units per day subcutaneously. Doses of IFN-alpha or placebo were modified according to predefined laboratory and clinical criteria. Therapy lasted at least 12 weeks. MEASUREMENTS AND MAIN RESULTS: Seventeen patients were randomly assigned to each group. The two groups had similar mean CD4 counts at study entry. Thirty-five percent of patients assigned to receive IFN-alpha withdrew from the study because of toxicity. The average daily dose of IFN-alpha was 17.5 x 10(6) units. All patients receiving IFN-alpha reported flu-like symptoms; other toxicities included granulocytopenia (55%) and elevated liver enzyme levels (45%). While receiving IFN-alpha, 7 patients (41%) became HIV culture negative (three or more consecutive negative peripheral blood mononuclear cell cultures taken at least 2 weeks apart). In contrast, 2 patients in the placebo group (13%) became culture negative while on study (P = 0.05). During the treatment period, CD4 lymphocyte percentages were sustained at or above the baseline level in patients receiving IFN-alpha and declined slightly in patients receiving placebo. Of the 32 study patients followed after study (range, 5 to 33 months), no patients in the IFN-alpha group developed an acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection, compared with 5 patients in the placebo group (P = 0.02). CONCLUSIONS: Treatment of early-stage HIV infection with IFN-alpha can result in a decrease in frequency of viral isolation. Although its use may be accompanied by dose-dependent toxicities, IFN-alpha may have a role in slowing progression of HIV disease.

Adolescent↗
PubMed1979

Granulocyte function during lithium therapy.

Random migration, chemotaxis, phagocytosis, and bactericidal ability of neutrophils from 5 patients receiving lithium carbonate were compared with those of neutrophils from healthy donors. These cells functioned normally in all respects. Neither sera from patients receiving lithium carbonate nor the addition of lithium chloride to control cells in vitro significantly altered their functional capacity. These findings suggest that neutrophil function in patients receiving lithium therapy is preserved, and they support the potential utility of this drug as a leukopoietic agent in neutropenic states.

Adult↗
PubMed1978

Inhibition of human granulocyte function by methotrexate.

Patients receiving cytotoxic drugs are at an increased risk of bacterial infection. Drug-induced leukopenia may be responsible for depression of host defenses; however, there is little information concerning the qualitative effects, if any, of cytotoxic agents on granulocyte antibacterial activity. Since methotrexate is now being used in massive doses in vivo, we investigated the effects of this drug on antibacterial and metabolic functions of normal polymorphonuclear leukocytes in vitro. Phagocytosis, quantitative protein iodination, and staphylococcal killing of normal polymorphonuclear leukocytes were found to decrease with exposure to increasing concentrations of methotrexate. The effects of methotrexate on these cell functions were rapid in onset and readily reversed by washing the cells, suggesting a locus of action on the cell membrane rather than at the level of nucleic acid synthesis. Exposure of cells to similar concentrations of folic acid or folinic acid produced no impairment of bacterial phagocytosis, suggesting that the observed effects are specific for methotrexate. The concentrations of methotrexate that produced these impairments are readily achieved in vivo and may alter antibacterial defenses in patients receiving this therapy.

Blood Bactericidal Activity↗
PubMed1977

H2O2 release from human granulocytes during phagocytosis. Relationship to superoxide anion formation and cellular catabolism of H2O2: studies with normal and cytochalasin B-treated cells.

Normal and cytochalasin B-treated human granulocytes have been studied to determine some of the interrelationships between phagocytosis-induced respiration and superoxide and hydrogen peroxide formation and release into the extracellular medium by intact cells. By using the scopoletin fluorescent assay to continuously monitor extracellular hydrogen peroxide concentrations during contact of cells with opsonized staphylococci, it was demonstrated that the superoxide scavengers ferricytochrome c and nitroblue tetrazolium significantly reduced the amount of H(2)O(2) released with time from normal cells but did not abolish it. This inhibitory effect was reversed by the simultaneous addition of superoxide dismutase (SOD), whereas the addition of SOD alone increased the amount of detectable H(2)O(2) in the medium. The addition of sodium azide markedly inhibited myeloperoxidase-H(2)O(2)-dependent protein iodination and more than doubled H(2)O(2) release, including the residual amount remaining after exposure of the cells to ferricytochrome c, suggesting its origin from an intracellular pool shared by several pathways for H(2)O(2) catabolism. When cells were pretreated with cytochalasin B and opsonized bacteria added, reduced oxygen consumption was observed, but this was in parallel to a reduction in specific binding of organisms to the cells when compared to normal. Under the influence of inhibited phagosome formation by cytochalasin B, the cells released an increased amount of superoxide and peroxide into the extracellular medium relative to oxygen consumption, and all detectable peroxide release could be inhibited by the addition of ferricytochrome c. Decreased H(2)O(2) production in the presence of this compound could not be ascribed to diminished bacterial binding, decreased oxidase activity, or increased H(2)O(2) catabolism and was reversed by the simultaneous addition of SOD. Furthermore, SOD and ferricytochrome c had similar effects on another H(2)O(2)-dependent reaction, protein iodination, in both normal and cytochalasin B cells. When oxygen consumption, O(2.) (-), and H(2)O(2) release were compared in the presence of azide under identical incubation conditions, the molar relationships for normal cells were 1.00:0.34:0.51 and for cytochalasin B-treated cells 1.00:0.99:0.40, respectively. Nonopsonized, or opsonized but disrupted, bacteria did not stimulate any of these metabolic functions. The results indicate that with normal cells approximately 50% of H(2)O(2) released during phagocytosis is derived directly from O(2.) (-) by dismutation, the remainder appearing from an (intra)cellular source shared by azide-inhibitable heme enzymes. With cytochalasin B treatment the evidence is consistent with the derivation of all H(2)O(2) from an O(2.) (-) precursor which is released from the cell surface. Furthermore, when activated by phagocytic particle binding, the neutrophil O(2.) (-) generating system appears to make more of this compound than can be accounted for by dismutation to H(2)O(2). This establishes conditions for the direct participation of both compounds in the microbicidal and cytocidal activity of these cells.

Azides↗