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D Hicks

Publications and source records attributed to D Hicks.

At least 127 records · Page 7Linked to original sources
PubMed1985

Immunoassay for the detection and quantitation of infectious human retrovirus, lymphadenopathy-associated virus (LAV).

Detection of replicating human retroviruses has relied upon rather cumbersome reverse transcriptase, immunofluorescence, or electron microscopic assays. We describe a new sandwich enzyme-linked immunoassay (ELISA) for detecting the human retrovirus, lymphadenopathy-associated virus (LAV), in supernates of LAV-infected human lymphocyte cultures. This LAV capture immunoassay compares favorably with the reverse transcriptase assay, despite the fact that it is performed on 20-fold less supernate material. Because the assay can be performed on 0.1 ml of culture supernate and is done by an ELISA method, LAV inoculation of lymphocyte cultures can be monitored quite conveniently, and endpoint titrations of infectious virus (ID-50 assays) can be performed. We demonstrate the application of the capture assay and ID-50 assay to disinfectant and serum neutralization experiments.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Effect of tolrestat on red blood cell sorbitol levels in patients with diabetes.

The effect of the aldose reductase inhibitor, tolrestat, on red blood cell (RBC) sorbitol levels was studied in 23 patients with diabetes after oral dosing with tolrestat, 25 or 100 mg b.i.d. The mean (+/- SE) RBC sorbitol levels (measured 12 hours after the preceding dose) after 3, 7, and 13 days of dosing decreased after both dose levels. After 25 mg tolrestat the RBC sorbitol levels fell from 25.1 +/- 4.0 to 20.0 +/- 5.7 nmol/gm hemoglobin (21%) and after 100 mg tolrestat the level fell from 26.7 +/- 3.7 to 11.4 +/- 1.7 nmol/gm hemoglobin (57%; P less than 0.001). This latter RBC sorbitol concentration is similar to levels in individuals without diabetes. At both dosage levels the maximum decrease in RBC sorbitol levels occurred after only 3 days of dosing. Tolrestat had no effect on plasma glucose or hemoglobin A1 concentrations. The overall mean plasma unbound drug concentration measured 12 hours after 100 mg tolrestat (11.7 +/- 3.0 ng/ml; 3.3 X 10(-8) mol/L) was similar to the median inhibitory level (3 X 10(-8) mol/L) of tolrestat for sorbitol accumulation in human RBCs incubated in a high-glucose medium. Our results demonstrate the systemic bioavailability of tolrestat and its aldose reductase inhibitory activity in erythrocytes of patients with diabetes.

Administration, Oral↗
PubMed1985

Localization of lectin receptors on bovine photoreceptor cells using dextran-gold markers.

Using a newly developed dextran-gold particle preparation combined with both pre- and post-embedding labeling techniques, three lectins were investigated for their surface and intracellular binding patterns in bovine retinal photoreceptor cells. Concanavalin A staining revealed heavy labeling of both the inner and outer segment plasma membranes (preembedded labeling), and intense labeling of the outer segment with lower levels in the inner segment (postembedded labeling). Rods and cones had similar patterns. Ricinus communis agglutinin-120 revealed only sparse to moderate labeling of the rod inner and outer segments (preembedded labeling). Much heavier labeling was apparent on the cone outer and inner segments. Direct labeling of thin sections revealed generally sparse labeling of inner and outer segments, but there was a noticeably greater intensity of binding in the basal region of rod outer segments. Wheat germ agglutinin revealed heavy labeling of rod and cone outer segments, with much reduced binding in the corresponding inner segments (preembedded labeling). A similar pattern was visible in directly labeled thin sectioned tissue, with the additional appearance of heavy binding to the proximal region of the connecting cilium. This latter binding is suggestive of a specialized connecting cilium region, possibly involved in regulation of rhodopsin transport to or prevention of backflow from the outer segment.

Animals↗
PubMed1985

Cellular tropism of the human retrovirus HTLV-III/LAV. I. Role of T cell activation and expression of the T4 antigen.

In cultures of normal human lymphocytes infected with the human retrovirus HTLV-III/LAV, detectable cytoplasmic virus appears and then disappears in a proportion (1 to 10%) of cells, followed by release of virus detected by particulate reverse transcriptase activity, virus antigen assay, and infectivity titer. Virus infection is associated with loss of detectable T4 antigen on infected cells and, ultimately, complete loss of T4+ cells from the culture. Residual non-T4+ cells are not susceptible to a second infection with HTLV-III/LAV, and in cultures of separated cell populations, substantial virus replication occurred in T4+ T cells and minimally, if at all, in non-T4+ cells. We could not detect a disproportionate loss of cell surface phenotype (other than T4) in comparison of infected and noninfected cultures of lymphocytes or purified T4+ T cells when these cultures were monitored with a panel of monoclonal antibodies that detect the major mononuclear cell types (alpha-T11, alpha-T3, alpha-Mo2, alpha-B1), functional T cell subsets (alpha-T8, alpha-Leu-8, alpha-T17), or activated/proliferating cells (alpha-T10, alpha-Ia, alpha-T9, alpha-4F2, alpha-Tac). HTLV-III/LAV replication was quantitatively greatest in lymphocytes stimulated with phytohemagglutinin (PHA) and cultured in the presence of interleukin 2 (IL 2). Once activated by PHA, virus production in nondividing (irradiated) cells was similar to that in nonirradiated cells, but was substantially reduced if radiation was performed before PHA stimulation. Omission of PHA, IL 2, or both resulted in progressively lower amounts of virus replication. However, virus replication was detected and T4+ T cell depletion occurred in all cultures, regardless of medium supplement or radiation. T4+ T cells absorb infectious virus, and the binding of HTLV-III/LAV to the surface of T4+ T cells, but not to non-T4+ cells, was directly demonstrated. Binding is equivalent in activated and nonactivated cells and at 4 degrees and 37 degrees C. Reciprocal inhibition of binding was observed with alpha-T4a monoclonal antibody and virus. Exposure of cells to alpha-T4a before and during HTLV-III/LAV inoculation inhibited subsequent virus replication. We conclude that T4+ T cells are the major target for HTLV-III/LAV replication, that this tropism is related to expression of the T4 antigen that serves as a binding site for virus, that infection is inexorable in T4+ T cells regardless of subset or activation state, and that the activation/proliferative state of the cells is not a necessary determinant of infectivity, but rather, determines the amount of replication that will ensue.

Adsorption↗
PubMed1984

Improved survival of newborns receiving leukocyte transfusions for sepsis.

To determine the role of polymorphonuclear (PMN) leukocyte transfusions in neonates with sepsis, 23 consecutive newborns were prospectively randomly selected during an 18-month period in a treatment plan to receive polymorphonuclear leukocyte transfusions with supportive care or supportive care alone. Thirteen neonates received transfusions every 12 hours for a total of five transfusions. Each transfusion consisting of 15 mL/kg of polymorphonuclear leukocytes was subjected to 1,500 rads of radiation. The polymorphonuclear leukocytes were obtained by continuous-flow centrifugation leukapheresis and contained 0.5 to 1.0 X 10(9) granulocytes per 15 mL with less than 10% lymphocytes. Pretreatment demographic, clinical, and laboratory variables that were found to be insignificant in prognosis between newborns who received transfusions and newborns who did not receive transfusions included weight, gestational and postnatal age, hypoxia, acidosis, hypotension, initial absolute granulocyte count (AGC), initial levels of immunoglobulins (IgA, IgG, and IgM), and total hemolytic complement. Positive findings on blood cultures were obtained in 14/23 patients and seven were randomly selected for each treatment group. Absolute granulocyte counts were less than 1,500/microL in 13 patients but tibial bone marrow examinations revealed that the neutrophil supply pool was depleted in only three patients. The survival was significantly greater in the treatment group (13/13, 100%) compared with the group that did not receive transfusions (6/10, 60%, P less than .02).(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗
PubMed1983

Absorption and excretion of isosorbide dinitrate and isosorbide-2-mononitrate in dogs.

In a crossover design four male dogs were given orally or i.v. [14C]isosorbide dinitrate (ISDN) or [14C]isosorbide-2-mononitrate (2-ISMN) at a dose of 1 mg kg-1 (70-80 microCi). Virtually all of the oral dose was absorbed and all of the radioactivity was excreted in the urine. The profile of serum radioactivity was similar after all drug administrations. ISDN was rapidly denitrated, giving rise to isosorbide-5-mononitrate (5-ISMN) as a major metabolite, and 2-ISMN as a minor metabolite. The apparent elimination half-life from serum of 2-ISMN and 5-ISMN was 2-3 h. More than 50% of the serum radioactivity after [14C]2-ISMN was due to unchanged drug. The apparent volume of distribution of 2-ISMN averaged 8.3 litres. The results show that, in contrast to ISDN, administration of 2-ISMN resulted in relatively high unchanged drug levels in the serum; the disposition of radioactivity after [14C]ISMN was however similar to that after [14C]ISDN. The findings support the concept that the concentrations of ISDN, 2-ISMN and 5-ISMN in the blood are inversely related to the rates of denitration, and that the vascular activity of the nitrates of isosorbide relates to the rates of their dinitration.

Absorption↗
PubMed1982

Fine structure of Periplaneta americana neurons in long-term culture.

A new culture technique is described for dissociated ganglia of embryos of Periplaneta americana. Neurons obtained by the mechanical dissociation of ganglia from 23-26 day old embryos were grown for seven days in a combination of Schneider's Drosophila Medium and Eagle's Basal Medium and then transferred to a combination of Leibovitz's L-15 Medium and Yunker's Modified Grace's Medium supplemented with ecdysone. Neurons cultured in this way survived for periods in excess of one month. The cells had a typically neuronal ultrastructure and produced axonal processes that associated to form fibre bundles. Within these processes neurosecretory granules, dense-core vesicles and clear vesicles were found. In some instances these vesicles aggregated at points of contact between fibres giving the appearance of presynaptic endings. These cultures would appear to be suitable for pharmacological studies of the insect nervous system.

Animals↗
PubMed1978

The way ahead.

Explore the source record for details and available documents.

Community Health Nursing↗
PubMedDate not supplied

Flavopiridol induces apoptosis and caspase-3 activation of a newly characterized Burkitt's lymphoma cell line containing mutant p53 genes.

Burkitt's lymphoma cell lines have been important in vitro models for studying the pathogenesis of Burkitt's lymphoma (BL) and for exploring new treatment strategies. A new EBV(-) Burkitt's lymphoma cell line (GA-10) was established from a patient with a clinically aggressive, chemorefractory BL and characterized. Although functional p-glycoprotein could not be demonstrated by dye-efflux assays, both p53 genes were mutated in the GA-10 cells, perhaps contributing to the resistant phenotype of the original neoplasm. Two properties of BL cells which may be useful targets for novel cytotoxic therapeutics are their surface expression of CD77, the receptor for Shiga toxin (Stx), and their high rate of proliferation. Expression of CD77 on the GA-10 cells was heterogeneous in that certain subclones expressed high levels of CD77 and correspondingly exhibited strong growth inhibition by Stx while others showed low levels of CD77 expression and weak Stx-induced growth inhibition. Flavopiridol, a potent inhibitor of cell cycle progression through G1 and G2, induced cytotoxicity of the GA-10 cells with an LC(50) of approximately 40 nM vs 70 nM for HL-60 cells (P < 0.05). The concentrations of flavopiridol at which only 10% of the cells were viable (LC(10)) were approximately 280 nM for the GA-10 cells and 520 nM for the HL-60 cells (P < 0.05). Dose-related induction of apoptosis in response to flavopiridol was demonstrated in the GA-10 cells by morphology, TUNEL assay, and activation of caspase-3. Flavopiridol was also cytotoxic to seven other BL cell lines tested. These data suggest that flavopiridol may have therapeutic value in the treatment of Burkitt's lymphoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Effect of hyperglycemia and the aldose reductase inhibitor tolrestat on sural nerve biochemistry and morphometry in advanced diabetic peripheral polyneuropathy. The Tolrestat Study Group.

Tolrestat is a well tolerated nonhydantoin aldose reductase inhibitor that has been reported to improve nerve conduction in diabetic animals and humans. Its effects on nerve biochemistry and structure have not been studied in patients with diabetic neuropathy. Patients with advanced diabetic neuropathy treated with long-term open-label tolrestat were randomly assigned to continuation on drug treatment or to placebo-controlled drug withdrawal for 12 months. At the end of this period, sural nerve biopsies were obtained for measurement of glucose, sorbitol, and fructose content, and for detailed morphometric analysis. Tolrestat ameliorated the glucose-mediated increase in sorbitol and fructose in sural nerve tissue. No statistically significant differences in nerve morphometry emerged between the two groups; however, both treatment groups exhibited increased nerve-fiber regeneration and normalization of axo-glial dysfunction and segmental demyelination following long-term tolrestat treatment. These findings are similar to those previously reported in a placebo-controlled sequential nerve biopsy study with the aldose reductase inhibitor sorbinil. Thus tolrestat is a biochemically effective aldose reductase inhibitor in human diabetic nerve with potential therapeutic efficacy for diabetic neuropathy.

Aldehyde Reductase↗
PubMedDate not supplied

Fibroblast growth factor receptor 4 (FGFR4) is expressed in adult rat and human retinal photoreceptors and neurons.

The fibroblast growth factor (FGF) family, with its prototype members acidic FGF (FGF-1) and basic FGF (FGF-2), binds to four related receptor tyrosine kinases, termed FGFR1, R2, R3, and R4, expressed on most types of cells in tissue culture. In many respects, the FGFR appear similar to other growth factor receptors; thus, dimerization of receptor monomers on ligand binding is likely to be a requisite for activation of the kinase domains, leading to receptor trans-phosphorylation. Within the central nervous system (CNS), including retina, FGFR1 and R2 have been widely described as the predominant forms. FGFR4 is reported to be strongly expressed only during early stages of development, and apart from one small region (the lateral habenular nucleus) is not detectable in adult CNS. Screening of different neural and nonneural tissues by reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that whereas FGFR1 and R2 were strongly expressed in adult cortex, cerebellum, retina, and kidney, robust FGFR4 expression was only seen in retina and kidney. FGFR4 mRNA was present within fractions of the outer and inner nuclear layers isolated from adult rat retinas, and could also be detected in pure photoreceptor cultures prepared from young rat retinas. On the contrary, FGFR4 mRNA could not be detected in primary cultures of retinal Müller glia or pigment epithelium, indicating specific enrichment in retinal neurons. In situ hybridization studies of adult rat retina showed FGFR4 expression in all retinal cellular layers, especially prominent in the outer nuclear layer. FGFR4 protein was detected by immunoblotting of homogenates of rat retina, with specific antibody binding to bands at 115, 47, and 30 kDa. FGFR4 mRNA and protein were also reliably detected in postmortem adult human retina. The potential roles of these signal transduction molecules in FGF-induced biological responses in the retina are discussed.

Animals↗