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Biomedical subjects

D Ho

Publications and source records attributed to D Ho.

At least 19 recordsLinked to original sources
PubMed1995

Assessment of abdominal aortic aneurysm with magnetic resonance imaging.

Pre-operative imaging of abdominal aortic aneurysms (AAA) is important in determining suitability for operation and operative approach. Ultrasound imaging is an excellent screening modality but is relatively poor at identifying renal arteries and the extent of iliac involvement. Computed tomography scanning with intravenous contrast and arteriography are invasive modalities that are associated with a small risk. Magnetic resonance imaging (MRI) offers the potential of accurate anatomical definition without use of contrast agents and passage of an intra-arterial catheter. Eight patients who had their AAA evaluated with MRI are reported. All had renal arteries accurately defined, intra-aneurysmal thrombosis was well delineated, and iliac extension was correctly identified in four cases. The initial experience has been most encouraging and the authors consider that MRI may become the investigation of choice for pre-operative AAA assessment.

Aged↗
PubMed1994

Correlation of perinatal transmission of human immunodeficiency virus type 1 with maternal viremia and lymphocyte phenotypes.

OBJECTIVE: To determine whether maternal transmission of human immunodeficiency virus (HIV) is correlated with increased quantities of HIV, decreased frequencies of CD4+ T cells, or increased levels of CD8+ T cells in the transmitting mother. METHODS: Peripheral blood obtained from HIV-infected women at different times during pregnancy was used to measure quantitative cell-associated HIV-1 and CD3+CD4+ and CD3+CD8+ proportions; the plasma was used to perform measurements of quantitative viremia by culture and subsequently to measure quantitative HIV-1 ribonucleic acid levels. These measurements were analyzed with respect to their association with HIV transmission to the baby, which occurred in one fourth of the cases. The children were also studied to determine whether HIV-1 was detected near birth or not until 1 to 8 weeks of life. RESULTS: Increased clonal frequencies of HIV-1-infected peripheral blood mononuclear cells were found in mothers of infected children; fivefold fewer cells were required for a positive culture result (median cell numbers of 10(4.5) vs 10(5.2); p = 0.008). Higher frequencies of infected cells were seen in mothers of babies with evidence of infection at birth than in mothers of infected babies without evidence of infection at birth (p < 0.05). Plasma viremia was measured in 10% of cultures without regard to whether the mothers transmitted virus to their babies. Increased levels of ribonucleic acid as detected by the branched-chain DNA method were measurable more often (45% vs 17%) in the mothers of infected children than in mothers of uninfected children. Proportions of CD4+ and CD8+ T cells were indistinguishable in these two groups of women. CONCLUSIONS: Increased viremia was present in mothers who transmitted HIV to their offspring. This variable could be used to select women at highest risk of transmitting HIV to their offspring for treatment to decrease the HIV burden five-fold.

CD4-CD8 Ratio↗
PubMed1992

Phase I trial of a 72-h continuous-infusion schedule of fazarabine.

Fazarabine (Ara-AC), a structural analog derived from the antitumor nucleoside cytosine arabanoside (Ara-C) and 5-azacytidine (5-AC), was studied in a phase I clinical trial. Doses ranging from 0.2 to 2.0 mg m-2 h-1 were given intravenously over 72 h every 28 days. The maximum tolerated dose (MDT) was 2.00 mg m-2 h-1. The dose-limiting toxicity was myelosuppression, with granulocytopenia being quantitatively more important than thrombocytopenia or anemia. Nonhematologic toxicity was minimal. Associated with the solvent dimethylsulfoxide (DMSO) was a bitter taste and a garlic-like odor.

Adult↗
PubMed1992

Relationship of the human immunodeficiency virus type 1 gp120 third variable loop to a component of the CD4 binding site in the fourth conserved region.

Neutralizing antibodies that recognize the human immunodeficiency virus gp120 exterior envelope glycoprotein and are directed against either the third variable (V3) loop or conserved, discontinuous epitopes overlapping the CD4 binding region have been described. Here we report several observations that suggest a structural relationship between the V3 loop and amino acids in the fourth conserved (C4) gp120 region that constitute part of the CD4 binding site and the conserved neutralization epitopes. Treatment of the gp120 glycoprotein with ionic detergents resulted in a V3 loop-dependent masking of both linear C4 epitopes and discontinuous neutralization epitopes overlapping the CD4 binding site. Increased recognition of the native gp120 glycoprotein by an anti-V3 loop monoclonal antibody, 9284, resulted from from single amino acid changes either in the base of the V3 loop or in the gp120 C4 region. These amino acid changes also resulted in increased exposure of conserved epitopes overlapping the CD4 binding region. The replication-competent subset of these mutants exhibited increased sensitivity to neutralization by antibody 9284 and anti-CD4 binding site antibodies. The implied relationship of the V3 loop, which mediates post-receptor binding steps in virus entry, and components of the CD4 binding region may be important for the interaction of these functional gp120 domains and for the observed cooperativity of neutralizing antibodies directed against these regions.

Animals↗
PubMed1991

Isolation of mitotic p34cdc2 apoenzyme from human cells.

A simple procedure was devised for isolating from homogenates of mitotic cells the human homolog to the fission yeast cdc2 gene product. The identity of the purified protein was established with anti-p34cdc2 antibodies and p13suc 1, both specific ligands for p34cdc2. Active-site labeling with oxidized [alpha 32P]ATP showed the purified molecule to be an ATP-binding protein. Its ability to phosphorylate casein but not histone, and its phosphorylation on tyrosine, detected by anti-phosphotyrosine antibodies, indicates the form of p34cdc2 purified is the inactive or apoenzyme form. Purified quantities of human p34cdc2 should be of considerable value in establishing the mechanism of its activation at mitosis by phosphatases.

Apoenzymes↗
PubMed1991

In vitro activity of cefpodoxime against bacterial isolates obtained from patients with cancer.

The in vitro activity of cefpodoxime, an oral cephalosporin ester, against 792 bacterial isolates representing 36 species was evaluated in comparison to that of ciprofloxacin and trimethoprim/sulfamethoxazole (TMP/SMX). Cefpodoxime inhibited the majority of Streptococcus spp., Haemophilus influenzae and Proteus mirabilis at a concentration of less than or equal to 0.12 microgram/ml. It was also active against Citrobacter diversus, Escherichia coli, Klebsiella spp., Proteus vulgaris, Serratia marcescens and methicillin-susceptible Staphylococcus aureus isolates. Overall, cefpodoxime appeared to be less active than ciprofloxacin and TMP/SMX against many pathogens common in cancer patients.

Bacteria↗
PubMed1986

Effects of various doses of latamoxef (moxalactam) on haemostasis.

The effects of intravenous latamoxef therapy at two doses of 3g and 6g daily for 7 days was assessed by various haemostatic parameters. With both doses, the prothrombin time, thrombin time and activated partial thromboplastin time remained within the normal range throughout the study. However, with the 6g day-1 dose there was a marked prolongation of the bleeding time associated with defective platelet aggregation to adenosine diphosphate and low dose collagen after 7 days therapy. With the 3g day-1 dose of latamoxef, there was no prolongation of the bleeding time and only minor changes in platelet aggregation responses.

Bleeding Time↗
PubMed1985

The haemostatic effects of hydroxyethyl starch (HES) used as a volume expander.

Hydroxyethyl starch (HES 450.000/0.7; Hespan 6.0 g/100 ml) was compared with standard crystalloid solutions in postoperative volume replacement in 20 patients undergoing routine orthopaedic surgery. The HES group showed no clinical evidence of haemorrhage and no laboratory evidence of significant haemostatic defects as assessed by standard coagulation tests, platelet aggregation and fibrinogen concentrations. There was a slight shortening in the thrombin time and a smaller increase in post-operative FVIII RAg and FVIII RCof levels in the HES group. HES is a safe and effective volume expander for postoperative use.

Adolescent↗
PubMed1985

Integration of a mutant c-Ha-ras oncogene into C3H/10T1/2 cells and its relationship to tumorigenic transformation.

C3H/10T1/2-CL8 mouse cells were shown to take up and express a plasmid-cloned drug resistance gene (Ecogpt) after DNA transfection at a frequency (2-6 X 10(-4) which is acceptable for routine recovery of gene-transformed populations. Transfection of 10T1/2 cells with a mutant c-Ha-ras oncogene (pEJ6.6 plasmid) results in neoplastically transformed 10T1/2 cell populations as judged by colony morphology and tumorigenic growth in nude mice. The levels of mutant c-Ha-ras gene integration and expression in the tumorigenic cell populations and 10T1/2 cell controls were determined, and the highest level of mutant ras transcript was seen in the most tumorigenic cell population. A preliminary comparison of 10T1/2 and NIH/3T3 cells showed similar frequencies for pEJ 6.6-induced transformed foci and a similar lack of sensitivity to the transforming effects of a cloned B-lym oncogene. The results identify a genetic event, which has previously been shown to be carcinogen-inducible, that is permissive for neoplastic transformation of the widely used carcinogen-transformable 10T1/2 mouse cell line.

Animals↗
PubMed1984

Modification of glutathione levels in C3H/10T1/2 cells and its relationship to benzo(a)pyrene anti-7,8-dihydrodiol 9,10-epoxide-induced cytotoxicity.

Levels of reduced glutathione (GSH) in C3H/10T1/2 cells were selectively altered to determine what quantitative role GSH transferase-catalyzed conjugation plays in regulating the cytotoxic effects of benzo(a)pyrene anti-7,8-dihydrodiol 9,10-epoxide (r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene, anti-diol epoxide). A 65% decrease in 10T1/2 cell GSH content from 0.16 mM (control cell GSH concentration) to 0.06 mM was accompanied by a 46% decrease in the anti-diol epoxide LD80; a 98% increase in GSH content resulted in a 44% increase in anti-diol epoxide LD80. This nonlinear relationship between changes in cellular GSH concentration and anti-diol epoxide LD80 was directly relatable to the nonlinear change in the rate of anti-diol epoxide conjugation which was catalyzed by 10T1/2 cell GSH transferases. Purified 10T1/2 cell cytosol catalyzed the GSH conjugation of anti-diol epoxide to yield a GSH conjugation product with a distinct UV absorbance spectrum; the apparent GSH Km for this cell cytosol-catalyzed reaction was 0.20 mM. Variations in the cellular GSH concentration around the GSH Km resulted in a nonlinear change in the amount of anti-diol epoxide-GSH conjugate formed, and a reciprocal change in the amount of free anti-diol epoxide available for cytotoxic alkylation events. These results clarify in quantitative, biochemical terms how GSH transferase-catalyzed conjugation can regulate the level of an electrophilic carcinogen metabolite in a biological system.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1984

Recombination following transformation of Escherichia coli by heteroduplex plasmid DNA molecules.

Circular heteroduplex DNA molecules introduced into Escherichia coli-competent cells are converted to new recombinant plasmids as a result of enzymatic actions in vivo. A pair of plasmids with partial sequence homology were each linearized at a different position with restriction enzymes, and the termini were made flush with the single-strand-specific S1 nuclease. Duplex molecules were then formed by melting and annealing these plasmid DNAs together. In contrast to linear homoduplex molecules, heteroduplexes circularize and therefore transform E. coli efficiently. Unique DNA sequences on each of the parental strands in the transforming heteroduplexes can be selectively incorporated or deleted as a result of in vivo enzymatic activities in transformed cells. This method permits the generation of new recombinant sequences in vivo without relying solely on the presence of convenient restriction sites for manipulation of DNA fragments in vitro.

DNA Restriction Enzymes↗
PubMed1984

Quantitative significance of glutathione and glutathione-S-transferase in regulating benzo[a]pyrene anti diol-epoxide level in reconstituted C3H/10T1/2 cell lysates, and comparison to rat liver.

Induced 10T1/2 cell microsomes were independently reconstituted with [3H]benzo[a]pyrene (BP) and glutathione (GSH) or purified GSH-transferases. Levels of the primary BP anti 7,8-dihydrodiol 9,10-epoxide (r-7,t-8 dihydroxy-t-9,10-oxy-7,8,9,10 tetrahydrobenzo[a]pyrene) hydrolysis product, 7,10/8,9-tetrol, were measured in incubation extracts, enabling us to monitor the level of free anti diol-epoxide in incubations and to determine the independent effects of GSH or GSH-transferases upon it. GSH alone had no effect on anti diol-epoxide levels over the concentration range tested (0-4.0 mM), however, the addition of purified GSH-transferase from rat liver resulted in a dose-dependent conjugation of anti diol-epoxide as well as 9,10-epoxide and 7,8-epoxide with 50% conjugation occurring at 0.036, 0.039 and 0.17 units GSH-transferase/ml, respectively. Free anti diol-epoxide was reduced by greater than 95% when we reconstituted with the GSH-transferase concentration which we measured in 10T1/2 cells (0.15-0.27 units/ml cell cytosol); this GSH-transferase concentration represents only 6% of that found in rat liver. The results suggest that in both 10T1/2 cells and rat hepatocytes GSH-transferase catalyzed GSH conjugation is quantitatively significant in determining the intracellular level of anti diol-epoxide.

Animals↗
PubMed1981

Beta-endorphin-induced increases in plasma epinephrine, norepinephrine and dopamine in rats: inhibition of adrenomedullary response by intracerebral somatostatin.

Synthetic human beta-endorphin, 7.25 nmol intracisternally, in unanesthetized, freely moving, chronically cannulated, adult male rats increased plasma concentrations of all 3 catecholamines: epinephrine, norepinephrine and dopamine, for the 2 h period studied. Blockade of these endorphin effects by the prior systemic administration of naloxone supports mediation of the effects at opioid receptors. Acute systemic administration of guanethidine, which decreases norepinephrine release induced by sympathetic nerve stimulation, blunted the plasma norepinephrine response to intracerebral beta-endorphin. Thus, it seems likely that in addition to secretion by adrenal medulla a considerable portion of the beta-endorphin-induced increase in norepinephrine is derived from sympathetic nerve endings. Simultaneous intracisternal administration of another neuropeptide, somatostatin, together with beta-endorphin markedly inhibited the plasma epinephrine response to beta-endorphin, while decreasing the dopamine and norepinephrine responses to a much lesser degree. The dats suggest that beta-endorphin stimulates central sympathetic outflow to both adrenal medulla and sympathetic nerve endings, and further that somatostatin inhibits the effect of endorphin to stimulate outflow to adrenal medulla but does not affect outflow to sympathetic nerve endings.

Adrenal Medulla↗
PubMed1981

beta-Endorphin-induced stimulation of central sympathetic outflow: beta-endorphin increases plasma concentrations of epinephrine, norepinephrine, and dopamine in rats.

Intracisternal administration of synthetic human beta-endorphin (0.058-7.25 nmol) in chronically cannulated, conscious, freely moving, adult male rats increased plasma concentrations of epinephrine, norepinephrine, and dopamine in a dose-related manner. Epinephrine secretion was the most sensitive to the stimulatory effect of intracerebral beta-endorphin; plasma epinephrine increased transiently in response to 0.058 nmol. Of the three catecholamines, plasma epinephrine showed the greatest and most rapid response to the largest dose (7.25 nmol) studied. Plasma norepinephrine increased significantly in response to 1.45 nmol, peaking later than plasma epinephrine. Plasma dopamine increased only in response to the highest dose examined. These beta-endorphin effects on plasma catecholamines were inhibited by intraarterial naloxone (1.1 mumol/kg), supporting mediation at opioid receptors. Pretreatment with the ganglionic blocking agent chlorisondamine inhibited the responses of all three catecholamines to intracisternal beta-endorphin. Bilateral adrenal denervation completely prevented the plasma epinephrine response to beta-endorphin and blunted the plasma norepinephrine and dopamine responses. Prior intracisternal administration of hemicholinium-3 blocked the plasma responses of all three catecholamines to intracisternal beta-endorphin, providing evidence for the involvement of central cholinergic neurons in the mechanism mediating beta-endorphin-induced increases in plasma catecholamines. The data are consistent with the hypothesis that endorphins act at a presently unknown brain site(s) to increase the central sympathetic outflow to adrenal medulla and peripheral sympathetic nerve endings, thus stimulating peripheral catecholamine release and increasing plasma concentrations of epinephrine, norepinephrine, and dopamine.

Animals↗