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L Walker

Publications and source records attributed to L Walker.

At least 109 records · Page 6Linked to original sources
PubMed1992

Localized conformational changes in the N-terminal domain of CD4 identified in competitive binding assay of monoclonal antibodies and HIV-1 envelope glycoprotein.

The CD4 antigen is established as a major cellular receptor for the human immunodeficiency virus (HIV). Previous studies have suggested that certain anti-CD4 monoclonal antibodies (MAbs) can inhibit or enhance the binding of the viral envelope glycoprotein gp120 to CD4 by allosteric effects. In the study reported here, 17 anti-CD4 MAbs were tested for their ability to influence the binding of each other to recombinant soluble CD4 in a solid-phase radioimmunoassay. Marked enhancement of binding between specific pairs of MAbs was seen, as well as inhibition or lack of interaction. Enhancement was seen less often when CD4+ cells were used as the target antigen. Information on patterns of enhancement and inhibition permitted grouping of MAbs on the basis of epitope specificity, and this grouping was in agreement with published findings based on X-ray crystallographic studies. These results demonstrate connectivity between epitopes in the first domain of recombinant CD4 and suggest a high degree of flexibility of surface structure. These findings may be of physiological significance both in the normal function of CD4 and in the interaction of CD4 with HIV. The data have implications for research or therapeutic strategies based on recombinant CD4 or CD4 mutants and highlight the problems of interpreting experimental findings based on abrogation of MAb binding.

Antibodies, Monoclonal↗
PubMed1992

Inhibitory activity of HIV envelope gp120 dominates over its antigenicity for human T cells.

HIV-1 envelope glycoprotein (gp120), as a CD4-binding reactant, has been shown to inhibit in its native form human T cell responses to several antigens. Here we show that gp120 in soluble form also inhibits activation of a specific human T cell line that responds to gp120-pulsed autologous antigen-presenting cells. In addition the inhibitory property of gp120 for antigen-driven T cell proliferation depends upon its ability to bind CD4 and is lost when CD4-binding capacity is abolished by denaturation, or blocked by complexing with soluble CD4 or with polyclonal antibodies. In contrast, antigenicity of denatured or complexed gp120 for specific human T cells is preserved. Similar effects are also observed with another CD4-binding reactant (i.e. anti-Leu 3a MoAb), which stimulates and/or inhibits human T cells specific for mouse immunoglobulins depending on native or denatured conformation.

Antibodies, Monoclonal↗
PubMed1992

Power to the portables.

Portable computing devices generally are classified into four categories: laptop, palmtop, notebook, and pen-based computers. If a portable unit weighs over eight pounds, call it a laptop. If a stylus is used to input data, call it pen-based or a pen computer. Palmtops frequently are electronic organizers or resources: Sharp's Wizard line stores appointments and addresses; Franklin's Med-Spell contains Stedman's medical dictionary. Notebooks often incorporate a QWERT keyboard, and sometimes include a pointing device. NEC's notebooks in 1988 were the first sub-laptop computers. According to a 1992 report from Market Intelligence Research Corp., Mountain View, Calif., 4.6 million sub-laptops were sold in 1991 for $2.6 billion. By 1998 the market may reach $25 billion. The report predicts that one sub-category of pen computers, which are designed to be held in one hand while information is input with a pen-like stylus, will prove most useful to the health-care industry. Pen tablets, as opposed to pen clipboards, use faster, more expensive processors, store more data, and "are expected to allow [caregivers] to carry full patient charting with them ... and allow information to be recorded directly to patient files." Sub-laptops are on-line in many healthcare facilities: Greenwich hospital, Stanford University Medical Clinic, Humana Hospital Audubon, Rancho Los Amigos Medical Center, and others.

Catalogs, Commercial as Topic↗
PubMed1991

Nucleotide sequence and expression of the human gene encoding apolipoprotein H (beta 2-glycoprotein I).

Human apolipoprotein H (ApoH), also called beta 2-glycoprotein I, is a 50-kDa serum glycoprotein whose function is not clearly defined. We have cloned and sequenced ApoH cDNAs both from human liver and from a human hepatoma cell line (HepG2). Both cDNA sequences predict a protein 345 amino acids (aa) in length. This sequence includes a 19-aa hydrophobic, N-terminal signal sequence which is not present in the mature protein [Lozier et al., Proc. Natl. Acad. Sci. USA 81 (1984) 3640-3644]. It differs from this previously reported aa sequence at two positions, both of which strengthen the conservation among the four short consensus repeats within the ApoH molecule. COS-1 cells transiently transfected with the ApoH cDNA in a eukaryotic expression vector produced a single species of ApoH mRNA and secreted in the ApoH protein. The level of ApoH mRNA expressed by HepG2 cells is downregulated by incubation with inflammatory mediators, implying that ApoH is a negative acute-phase protein.

Acute-Phase Reaction↗
PubMed1991

Phenotypic inhibition of the renin-angiotensin system, emergence of the Ren-2 gene, and adaptive radiation of mice.

The renin-angiotensin system in sub-genus Mus displays unique features including duplication of the renin gene in most strains, strong expression of the second gene in submandibular gland of males, and inhibited responses to injected renin. Our findings indicate that this inhibition results from a paucity of renin substrate and is consistent with first-order kinetics. We find substrate paucity to be a feature of both sexes and all sub-species and strains of Mus irrespective of gene duplication. Attempts to increase the level of substrate in blood by intravenous injection caused marked increases in blood pressure in Mus, suggesting that substrate paucity was a phenotypic prerequisite for successful emergence of enhanced renin expression in salivary gland. We propose that these phenomena are linked to salivary "lethal factor", possibly transferred by biting, in an evolutionary sequence that has provided a major selective advantage for Mus and influenced the ecology and evolution of rodents.

Angiotensinogen↗
PubMed1991

Rectal bioavailability of delta-9-tetrahydrocannabinol from various esters.

The bioavailability of delta-9-tetrahydrocannabinol (delta 9-THC) from suppository formulations containing several polar esters was studied. The esters tested were the hemisuccinate, N-formyl alaninate, N-methyl carbamate, and methoxy acetate. These esters were administered to monkeys in both lipophilic and hydrophilic suppository bases, namely, Witepsol H15 and polyethylene glycol, respectively. Each suppository contained a dose equivalent to 10 mg delta 9-THC. Blood samples were analyzed for both delta 9-THC and its carboxylic acid metabolite (ll-nor-delta 9-THC-9-COOH) using gas chromatography/mass spectrometry. The data showed that, with the exception of the hemisuccinate, no delta 9-THC or its metabolite was detected in the blood samples using the Witepsol H15. Using polyethylene glycol, low levels of delta 9-THC and its metabolite were detected in blood for all esters tested. The levels, however, were lower than those observed with delta 9-THC hemisuccinate using Witepsol H15. Subsequent studies in the conscious dog using the hemisuccinate in Witepsol H15 showed 67% bioavailability of delta 9-THC with a linear response in the dose range equivalent to 5-20 mg of delta 9-THC. No significant bioavailability differences were found when delta 9-THC hemisuccinate ester was administered in various lipophilic bases (Hydrokote 25, Kaomel, Suppocire AIML, and Witepsol H15).

Administration, Rectal↗
PubMed1991

Ethanol influences class I and class II MHC antigen expression on human fetal islet-like cell clusters.

Several autoimmune diseases have been linked to an aberrant expression of major histocompatibility complex (MHC) products Ethanol enhances Class I and Class II products on a variety of cell types, and there is evidence for an autoimmune etiology in numerous pathologies associated with alcoholism. We examined whether ethanol alters the expression of Class I and Class II MHC products on human fetal islet-like cell clusters. Incubation of islet-like clusters for 48 hr in ethanol at a starting concentration of 1.5% increased the percentage of single cells expressing Class I. The percentage of cells expressing Class II did not change, but their relative mean fluorescence increased significantly. These findings suggest that alcohol ingestion could alter MHC expression on pancreatic islet cells in vivo perhaps affecting the development of diabetes in genetically predisposed individuals. These findings also support the hypothesis that the rising incidence of type 1 diabetes seen in areas of the world where the per capita consumption of alcohol is also increasing may be a consequence of the immunological effects of alcohol intake.

Ethanol↗
PubMed1991

Prohibitin, an evolutionarily conserved intracellular protein that blocks DNA synthesis in normal fibroblasts and HeLa cells.

Genes that act inside the cell to negatively regulate proliferation are of great interest because of their implications for such processes as development and cancer, but these genes have been difficult to clone. This report details the cloning and analysis of cDNA for prohibitin, a novel mammalian antiproliferative protein. Microinjection of synthetic prohibitin mRNA blocks entry into S phase in both normal fibroblasts and HeLa cells. Microinjection of an antisense oligonucleotide stimulates entry into S phase. By sequence comparison, the prohibitin gene appears to be the mammalian analog of Cc, a Drosophila gene that is vital for normal development.

Amino Acid Sequence↗
PubMed1991

Windows on Henry Ford.

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Computer Communication Networks↗