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Biomedical subjects

G Brown

Publications and source records attributed to G Brown.

At least 19 recordsLinked to original sources

Immune suppression in BALB/c mice bearing the plasmacytoma TEPC-183: evidence for normal lymphocyte but defective macrophage function.

This paper analyses impairment of the primary immune response of mice bearing the plasmacytoma TEPC-183. Healthy animals and mice bearing the reported non-immunosuppressive tumour MOPC-104E were used as controls. The defect was shown to affect both primary IgG and IgM responses to chicken cells (CRBC) and to be related to tumour size. However, the primary immune depression could be overcome either by increasing the antigen dose or by using Freund's complete adjuvant together with antigen. Secondary responses were also depressed. This depression was more pronounced if the animals was primed after, rather than before, tumour implantation. Further studies involved the measurement of primary immune responses of immunologically deprived syngeneic mice, after they had been reconstituted with cells from normal or tumour-bearing mice. Lymphocyte reconstitution experiments were carried out in mice which had been irradiated with 950R. Various lymphoid preparations from TEPC-183-bearing mice were unable to bring about such restoration. It is concluded that the impairment of the primary immune response of mice bearing the plasmacytoma TEPC-183 is due to a macrophage, rather than a lymphocyte, abnormality. However, none of these transfer studies suggested that positive suppression of primary immune responses was being mediated by cells from TEPC-183-bearing mice.

Animals

The carbohydrate prosthetic groups of rat fibrinogen plasmic fragment E.

Rat fibrinogen plasmic fragment E was found to contain one oligosaccharide chain per gamma-chain attached by a glycosylamine linkage. The oligosaccharide was composed of 1 sialic acid, 1 galactose, 2 mannose and 2 glucosamine residues. The probable sequence from the nonreducing end was sialic acid leads to galactose beta leads to mannose alpha leads to mannose alpha leads to glucosamine leads to glucosamine. No difference in the rate of clearance from the rat circulation could be detected between native and desialated fragment E. A non-denaturing method for the purification of fragment E is described.

Animals

The distribution of HLA on human lymphoid, bone marrow and peripheral blood cells.

The cellular distribution and the differential expression of HLA on cell suspensions and tissue sections has been investigated using the monoclonal antibody W6-32, which reacts with the high molecular weight chain of the major histocompatibility antigen. Lymphocytes and platelets, as assessed by autoradiographic and immunoperoxidase labeling, were the most densely labeled cells. Myeloid precursors showed more labeling than mature neutrophils. Electron microscopic immunoperoxidase labeling showed a continuous distribution of HLA antigen on lymphoid and myeloid cell membranes. Erythroid precursors (including reticulocytes), although very weakly labeled, were clearly positive, in comparison with mature erythrocytes. In the thymus, HLA-negative, thymocyte antigen-positive cells (85%) can be distinguished from HLA-positive, thymocyte antigen-negative cells (15%). By using immunofluorescence techniques on tissue sections, the former cells were shown to be cortical thymocytes and the latter medullary cells.

Antigens, Surface

Antibodies in human sera reacting with an insect pathogenic virus.

Precipitating antibodies to an insect pathogenic RNA virus of Darna trima from East Malaysia have been found in a small percentage of human sera from several different groups of persons in West Malaysia and the United Kingdom. No associated illness was identified. The results suggest that an antigenically related virus or viruses are present in the environment that may be associated with symptomless or inapparent infections in man.

Adolescent

A morphometric study of arterial intimal thickening in kidneys of dialyzed patients.

Arterial intimal thickening is common in the end-stage kidneys of patients maintained on hemodialysis. We measured the intimal thickening in patients dialyzed for varying periods and in patients with the malignant phase of essential hypertension and with scleroderma-associated renal failure. The ratio of intimal area to medical area in intrarenal arteries was used as a measure of intimal thickening. In the dialysis groups, intimal thickening was relatively constant in arteries of all sizes and correlated with duration of dialysis, particularly in larger arteries. In the malignant hypertension and scleroderma groups, the intimal thickening was greatest in arteries less than 200 mu in diameter and least in those over 500 mu in diameter. There was much less intimal thickening in arteries of all sizes in kidneys of patients with end-stage polycystic disease than in other end-stage kidneys from patients with a similar diastolic blood pressure and similar duration of dialysis. We believe that the intimal thickening in dialyzed patients is probably a disuse type of change and may be related to reduction in the area of the renal microvascular bed.

Adolescent

Fetal hyperinsulinism in rhesus isoimmunization.

Analyses of peritoneal ascitic fluid obtained prior to intrauterine transfusion show that some babies with severe rhesus isoimmunization develop raised insulin levels up to a month before delivery. The glucose content of fetal ascitic fluid is usually only about 10 mg. per 100 ml. less than the glucose content of maternal plasma and there is no evidence that this relation is influenced by the fetal or maternal insulin level. The electrolyte content of fetal ascitic fluid is very similar to that of maternal plasma, but fluid from babies with hyperinsulinism has an unusually high calcium content.

Ascitic Fluid

Hypopharyngeal perforations in neonates.

Hypopharyngeal perforations in the neonate have rarely been reported, although such a disorder may be a more common occurrence than suspected. The optimal therapy is controversial. A case is presented in which instrumentation of the upper airway led to a transmural hypopharyngeal perforation in a naonate. The infant did well with conservative therapy. The early recognition of hypopharyngeal lacerations is of great importance. When the correct diagnosis is made, the condition of infants with pseudodiverticulum of the hypopharynx can be managed successfully without surgery.

Diverticulum

Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-new tools for genetic analysis.

Antibody-secreting hybrid cells have been derived from a fusion between mouse myeloma cells and spleen cells from a mouse immunized with membrane from human tonsil lymphocyte preparations. Hybrids secreting antibodies to cell surface antigens were detected by assaying culture supernatants for antibody binding to human tonsil cells. Six different antibodies (called W6/1, /28, /32, /34, /45 and /46 were analyzed. These were either against antigens of wide tissue distribution (W6/32, /34, and /46) or mainly on erythrocytes (W6/1 and W6/28). One of the anti-erythrocyte antibodies (W6/1) detected a polymorphic antigen, since blood group A1 and A2 erythrocytes were labeled while B and O were not. Antibodies W6/34, /45 and /46 were all against antigens which were mapped to the short arm of chromosome 11 by segregation analysis of mouse-human hybrids. Immunoprecipitation studies suggest that W6/45 antigen may be a protein of 16,000 dalton, apparent molecular weight, while W6/34 and /46 antigens could not be detected by this technique. Antibody W6/32 is against a determinant common to most, if not all, of the 43,000 dalton molecular weight chains of HLA-A, B and C antigens. This was established by somatic cell genetic techniques and by immunoprecipitation analysis. Tonsil leucocytes bound 370,000 W6/32 antibody molecules per cell at saturation. The hybrid myelomas W6/32 and W6/34 have been cloned, and both secrete an IgG2 antibody. W6/32 cells were grown in mice, and the serum of the tumor-bearing animals contained greater than 10 mg/ml of monoclonal antibody. The experiments established the usefulness of the bybrid myeloma technique in preparing monospecific antibodies against human cell surface antigens. In particular, this study highlights the possibilities not only of obtaining reagents for somatic cell genetics, but also of obtaining mouse antibodies detecting human antigenic polymorphisms.

Antibody Formation