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Biomedical subjects

M E North

Publications and source records attributed to M E North.

27 records · Page 2Linked to original sources
PubMed1983

Human B cell growth factors overcome T cell-mediated inhibition of specific antibody production: a possible mechanism for the exacerbation of autoimmune disease.

Under normal circumstances, antigen-dependent antibody production in man requires autologous T cells, B cells and macrophages. If allogeneic T cells are substituted, then antibodies are not synthesized, due to the development of inhibitory interactions. Addition of B cell growth and differentiation factors changes this pattern of response, and allows antibodies to be produced even when allogeneic T cells are the source of help. There is evidence that such B cell growth factors are released during most normal immune responses: we suggest that their ability to allow B cells to escape from inhibitory interactions and secrete antibodies, may underlie the observed exacerbation of certain autoimmune diseases by intercurrent infection.

Antibody Formation↗
PubMed1983

The interaction of specific T-cell help and non-specific B-cell growth factors in the production of anti-tetanus antibody by human B cells grown in serum-free microcultures.

Apart from a brief period after in-vivo immunization, only a minority of human donors provide peripheral lymphocytes that synthesize specific antibody on stimulation with tetanus toxoid in vitro. A 20 microliters hanging drop microculture technique using serum-free medium has been adapted to analyse the conditions under which B cells mature into antibody-secreting cells. Multiple permutations of antigen dose, cell concentration and T:B cell ratios have been examined. The results indicate that in-vitro failure of antigen response by the majority of donors is not due simply to an inappropriate choice of culture conditions. The addition to antigen-stimulated cultures of a lectin-free conditioned medium derived from pokeweed mitogen-stimulated peripheral lymphocytes, enables B cells from the majority of donors to produce high titres of specific antibody, in a T-dependent manner, for up to 24 months after immunization. The observed failure of prolonged antigen responsiveness in vitro thus appears to represent a failure to expand a population of antigen-specific B cells, rather than indicating an absence of such clones.

Antibodies, Bacterial↗
PubMed1982

Bactericidal activity of serum for Klebsiella rhinoscleromatis: studies on serum from a patient with rhinoscleroma and sera deficient in antibody or complement.

The in-vitro bactericidal effect of serum for Klebsiella rhinoscleromatis was tested. Experiments with C2-deficient and hypogammaglobulinaemic human sera suggested that killing depended on activation of the classical complement pathway, although the alternative pathway probably amplified the effect. Serum from a patient with active rhinoscleroma, and another cured of the disease, showed normal killing.

Agammaglobulinemia↗
PubMed1982

Activities of enzymes involved in purine metabolism and some related adenine nucleotide concentrations of leucocytes in renal failure.

We have studied purine metabolism in mononuclear and polymorphonuclear cells from uraemic patients using microradiochemical enzyme assays and high-pressure liquid chromatography. In mononuclear cell lysates the mean activities of adenosine deaminase (EC 3.5.4.4) and 5'-nucleotidase (EC 3.1.3.5) were significantly diminished. The activities of adenylate kinase (EC 2.7.4.3), purine nucleoside phosphorylase (EC 2.4.2.1), adenine phosphoribosyltransferase (EC 2.4.2.7), and hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) were not significantly different in the two groups. The activities of adenosine deaminase and adenine phosphoribosyltransferase were reduced in the polymorphonuclear cell lysates. No clear differences emerged in the concentration of adenine nucleotides in the mononuclear cells. The significance of these changes, which are less marked than those in erythrocytes, is discussed with reference to the immunodeficiency associated with uraemia.

Adenine Nucleotides↗
PubMed1981

Effect of renal failure on erythrocyte purine nucleotide, nucleoside and base concentrations and some related enzyme activities.

1. We have studied purine metabolism in renal failure using high-pressure liquid chromatography to determine metabolite concentrations in erythrocytes and plasma, and microradiochemical assays of enzyme activity in erythrocytes. 2. The mean activities of some of the enzymes involved in purine metabolism were raised in renal failure. Significant elevations of adenylate kinase (EC 2.7.4.3), purine nucleoside phosphorylase (EC 2.4.2.1), hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) and adenosine deaminase (EC 3.5.4.4) but not of adenine phosphoribosyltransferase (EC 2.4.2.7) and ribosephosphate pyrophosphokinase (phosphoribosylpyrophosphate synthetase; EC 2.7.6.1) activities were demonstrated. However, there was an overlap between results from patients with renal failure and normal (control) subjects. Erythrocyte phosphoribosylpyrophosphate levels were also unchanged. 3. Erythrocyte nucleotide concentrations especially those of inosine were raised in renal failure. 4. The plasma inosine was reduced in renal failure. 5. The significance of these changes is discussed.

Adolescent↗
PubMed1980

Lymphocyte cyclic AMP levels in primary hypogammaglobulinaemia: lack of correlation with response to phytohaemagglutinin.

Normal levels of lymphocyte cyclic AMP were found in fourteen of fifteen patients with primary hypogammaglobulinaemia. One patient with adult-onset hypogammaglobulinaemia had low cyclic AMP levels with a very poor rise after prostaglandin E1 stimulation. Five of the patients had severely depressed thymidine uptake by their phytohaemagglutinin-stimulated lymphocytes but there was no significant difference between their lymphocyte cyclic AMP levels and those of patients with normal lymphocyte responses. Removal of monocytes from concanavalin A-stimulated lymphocyte cultures from three of these patients did not affect the severe depression of leucine uptake. These findings indicate that the depression of lymphocyte response to mitogens seen in some patients with late-onset primary hypogammaglobulinaemia is not due to raised levels of lymphocyte cyclic AMP; and not usually due to prostaglandins released by monocytes in the cultures.

Adult↗
PubMed1980

Phosphorylation of deoxyguanosine by B and T lymphocytes: evidence against selective trapping of deoxyguanosine by T lymphocytes in purine nucleoside phosphorylase deficiency.

T and B lymphocytes from blood and tonsils, as well as T and B lymphoid cell lines, phosphorylate deoxyguanosine which is probably the major toxic metabolite in purine nucleoside phosphorylase (PNP) deficiency. T and B cells also have similar activities of purine nucleoside phosphorylase. These findings indicate that the selective T cell defect in patients with PNP deficiency is unlikely to be due to a selective 'trapping' of deoxyguanosine by T lymphocytes.

Adenosine Deaminase↗
PubMed1977

Lymphocyte purine 5'-nucleotidase edficiency in primary hypogammaglobulinaemia.

The mean activity of purine 5'-nucleotidase (E.C.3.1.3.5) in lymphocytes was significantly lower in patients with non-familial adult onset "variable" primary hypogammaglobulinaemia than in non-hypogammaglobulinaemic control subjects. These findings suggest that 5'-nucleotidase activity is necessary for normal lymphocyte function. This may be related to its role in facilitating the transfer of newly formed purines across cell membranes by converting them from nucleotides to nucleosides. This enzyme defect may be a characteristic metabolic lesion in at least some of the patients; alternatively, it may be secondary to some other metabolic defect or plasma-membrane change.

Agammaglobulinemia↗