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Biomedical subjects

M Larkin

Publications and source records attributed to M Larkin.

At least 145 records · Page 8Linked to original sources
PubMed1989

Oligosaccharide-mediated interactions of the envelope glycoprotein gp120 of HIV-1 that are independent of CD4 recognition.

In this study carbohydrate-mediated interactions of the envelope glycoprotein, gp120, of HIV-1 were investigated. Oligosaccharide probes (neoglycolipids), prepared from the N-glycosidically-linked chains of the natural and recombinant forms of gp120, were used in conjunction with the intact glycoprotein to investigate reactivities with a soluble carbohydrate-binding protein (lectin) known as mannose-binding protein in human serum. Evidence is presented that the high-mannose-type oligosaccharides with seven, eight and nine mannose residues from both forms of gp120 are recognized by the serum lectin, and that these reactivities are unrelated to CD4 recognition. Reactivities of the two forms of envelope glycoprotein with macrophages derived from human blood monocytes and with the mannose-specific macrophage endocytosis receptor isolated from human placental membranes were also investigated. Evidence is presented that both forms of gp120 bind to the macrophage surface by multiple interactions in addition to CD4 binding, and that among these interactions is a carbohydrate-mediated binding to the endocytosis receptor. We propose that such carbohydrate-mediated interactions could form the basis of viral attachment to a variety of healthy and diseased tissues.

CD4 Antigens↗
PubMed1988

Carbohydrate structures of the human-immunodeficiency-virus (HIV) recombinant envelope glycoprotein gp120 produced in Chinese-hamster ovary cells.

The present paper describes the structures of the N-linked oligosaccharides of the human-immunodeficiency-virus (HIV) envelope glycoprotein gp120 (cloned from the HTLV-III B isolate and expressed as a secreted fusion protein after transfection of Chinese-hamster ovary cells), which is known to bind with high affinity to human T4-lymphocytes. Oligosaccharides were released from peptide by hydrazinolysis, fractionated by paper electrophoresis, high-performance lectin-affinity chromatography and Bio-Gel P-4 column chromatography, and their structures determined by sequential exoglycosidase digestions in conjunction with methylation analysis. The glycoprotein was found to be unique in its diversity of oligosaccharide structures. These include high-mannose type and hybrid type, as well as four categories of complex-type chains: mono-, bi-, tri- and tetra-antennary, with or without N-acetyl-lactosamine repeats, and with or without a core-region fucose residue. Among the sialidase-treated oligosaccharides, no less than 29 structures were identified as follows: (formula; see text) where G is galactose, GN is N-acetylglucosamine, M is mannose, F is fucose, and '+/- ' means that residues are present in a proportion of chains. The actual number of oligosaccharide structures is much greater, since before desialylation there was evidence that, among the hybrid and complex-type chains, all but 6% contained sialic acid at the C-3 position of terminal galactose residues, and partially sialylated forms of the bi- and multi-antennary chains were present. Detailed evidence for the proposed oligosaccharide sequences will be published as a supplementary paper [T. Mizuochi, M. W. Spellman, M. Larkin, J. Solomon, L. J. Basa & T. Feizi (1988) Biomed. Chromatogr., in the press].

Animals↗
PubMed1988

Structural characterization by chromatographic profiling of the oligosaccharides of human immunodeficiency virus (HIV) recombinant envelope glycoprotein gp120 produced in Chinese hamster ovary cells.

This report together with the paper by T. Mizuochi, M. W. Spellman, M. Larkin, J. Solomon, L. J. Basa and T. Feizi (1988) Biochem. J. 254, 599-603 describes the structural elucidation of the N-linked oligosaccharides of the HIV envelope glycoprotein, gp120 (cloned from the HTLV-III B isolate and expressed as a secreted fusion protein after transfection of Chinese hamster ovary cells), which is known to bind with high affinity to human T4 lymphocytes. Oligosaccharides were released from peptide by hydrazinolysis, fractionated by paper electrophoresis, high performance lectin affinity chromatography and Bio-Gel P-4 column chromatography, and their structures determined by sequential exoglycosidase digestions in conjunction with methylation analysis. The glycoprotein was found to be unique in its diversity of oligosaccharide structures. These include high-mannose type and hybrid type, as well as four categories of complex type chains: mono-, bi-, tri- and tetra-antennary, with or without N-acetyllactosamine repeats, and with or without a core region fucose residue. Among the sialidase-treated oligosaccharides no less than 29 structures were identified as follows: (formula; see text) where G = galactose; GN = N-acetylglucosamine; M = mannose; F = fucose; +/- = residues present in a proportion of chains. The actual number of oligosaccharide structures is much greater since before desialylation there was evidence that among the hybrid and complex type chains all but 6% contained sialic acid at the C-3 position of terminal galactose residues, and partially sialylated forms of the bi- and multiantennary chains were present.

Animals↗
PubMed1985

Antibody response to varicella-zoster virus surface glycoproteins in chickenpox and shingles.

Varicella-zoster virus (VZV)-infected cell surface proteins were investigated using extrinsic radiolabelling of the cell surface, immunoprecipitation of detergent-solubilized extract of the same cell surface and fractionation of the immunoprecipitates using SDS-PAGE. Glycosylated proteins were identified by their affinity for Ricinus communis lectin. Six glycoproteins with apparent mol. wt. of 170K, 105K, 93K, 81K, 53K and 45K were identified. The 170K glycoprotein was shown to be disulphide-linked since under reducing conditions for SDS-PAGE it was cleaved to a protein of 63K mol. wt. The IgG responses to these glycoproteins during various clinical circumstances are described. In acute sera from all chickenpox patients and in the majority of acute shingles sera, antibodies reactive with glycoproteins could not be detected. In chickenpox convalescence, antibodies reactive with glycoproteins of mol. wt. 170K, 105K, 53K and 45K were identified, whilst during zoster convalescence antibodies to all six were prominent. Antibodies to the disulphide-linked glycoprotein persisted for many years following both the primary disease and its reactivation. Disseminated zoster was associated with significantly low levels of antibodies to these surface glycoproteins.

Adult↗
PubMed1983

Effect of low dose acyclovir (5 mg/kg) on virus shedding, interferon and humoral immunity in herpes zoster.

In a double-blind randomized trial, virological studies were carried out in non-immunocompromised patients with herpes zoster who received either acyclovir (5 mg/kg) or placebo intravenously three times daily for five days. Mean duration of virus shedding was not significantly different in the two groups and all patients developed high titres of antibody to varicella-zoster virus. Interferon levels in vesicle fluid reached a peak significantly sooner (P less than 0.025) and at a lower level in eight treated patients compared with eight given placebo, corresponding with significantly earlier cessation of vesicle formation in the treated group (P less than 0.05). Pretreatment virus isolates tested for sensitivity to the drug showed ED50 values from 4 +/- 0.7 to 17.5 +/- 1 microM acyclovir. Treatment with a dose of acyclovir greater than 5 mg/kg, but not exceeding 10 mg/kg, is recommended for herpes zoster.

Acyclovir↗
PubMed1980

Visual fields interpretation.

From the retina to the visual cortex, commonly encountered visual field defects are discussed. Retinal, optic nerve nerve head, optic nerve, optic tract, lateral geniculate, radiations and cortex lesion examples are described with predicted outcomes and possible variations of the field defects.

Brain Diseases↗
PubMedDate not supplied

Triglyceride levels affect cognitive function in noninsulin-dependent diabetics.

Noninsulin-dependent diabetes mellitus (NIDDM) is associated with decrements in several cognitive functions. Among the variables that apparently contribute to the decline in cognitive performance is poor glucose control, as measured by hemoglobin A1c. Elevated levels of triglycerides in diabetics may also contribute to this cognitive decline through the increased incidence of atherosclerosis in these patients. The authors examined the relationship between triglycerides and cognitive performance in 246 NIDDM outpatients, aged 55-74 years. The relationship between triglyceride levels and performance on three cognitive tasks and on a test of reaction time was measured. Elevated levels of triglycerides were associated with significant decrements in performance on the digit symbol substitution test, digit span (backward) test, and on a reaction time measure. High levels of triglycerides, independent of chronic glucose control, appear to contribute to the decreased ability to perform short-term memory tasks in NIDDM.

Blood Glucose↗