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Biomedical subjects

A D Webster

Publications and source records attributed to A D Webster.

At least 181 records · Page 10Linked to original sources
PubMed1983

Increased serum concentration of T4-binding globulin in patients with hypogammaglobulinaemia.

Patients with hypogammaglobulinaemia have been regularly found to have abnormal conventional thyroid function test results. The abnormality is due to an increased plasma concentration of T4-binding globulin (TBG). As the prevalence of autoimmune thyroid disease is probably increased in hypogammaglobulinaemia this further abnormality in the plasma proteins may lead to diagnostic confusion. Administration of gammaglobulin by infusion causes a rapid but transient fall in plasma concentrations of TBG and T4 which is probably due to a temporary redistribution of the plasma proteins.

Agammaglobulinemia↗
PubMed1983

Primary late-onset hypogammaglobulinaemia associated with inflammatory polyarthritis and septic arthritis due to Mycoplasma pneumoniae.

A case is reported of primary late-onset hypogammaglobulinaemia associated with a chronic seronegative, nonerosive arthritis, which was complicated by an episode of septic arthritis due to Mycoplasma pneumoniae. The patient had subcutaneous nodules which have not been regarded previously as a feature of the chronic arthritis associated with hypogammaglobulinaemia. The diagnosis of septic arthritis was delayed for 2 months until synovial fluid was specifically cultured for mycoplasmas. This delay resulted in considerable joint destruction. The importance of searching for mycoplasmas in similar cases is emphasised.

Adult↗
PubMed1983

Serum immunoglobulin concentrations in preschool children measured by laser nephelometry: reference ranges for IgG, IgA, IgM.

Serum immunoglobulin concentrations were determined on sera from 298 healthy children aged six months to six years using the Hyland laser nephelometer PDQ system. Age-specific 95% reference ranges for serum IgG, IgA and IgM are presented; considerable care has been taken to ensure statistical validity of the reference ranges. The wide range of values in children under two years suggest that measuring immunoglobulin concentrations in this age group is of little value in diagnosing immunodeficiency.

Aging↗
PubMed1983

Effects of cyclosporin A on immunoglobulin production by EB virus stimulated lymphocytes.

Cyclosporin A (Cy A) enhances immunoglobulin (Ig) production by EB virus stimulated peripheral blood lymphocytes from normal subjects with prior immunity to EB virus. In 11 normal adults, this enhancement of Ig production correlated with T cell-mediated cytotoxic regression. Cultures from normal healthy adults without prior immunity showed a diminution of Ig production when Cy A was added. However, Cy A had no effect on Ig production by cord blood lymphocytes in the first week of culture but there was definite enhancement after 3 weeks. Cy A thus inhibits both the early phase of T cell help (which is lymphokine- or interferon-mediated) and the later phase of cytotoxicity manifested as regression. Furthermore, Cy A tended to inhibit IgG and IgA production in T depleted cultures, and had little effect on IgM or IgD, suggesting a differential effect on B cell subsets. These reactions to EB virus in vitro were investigated in two diseases in which EB virus immunity may be relevant. Six of 14 adult patients with primary hypogammaglobulinaemia showed no T cell-mediated regression nor Cy A enhancement, probably because of an underlying defect in both T and B cells. Regression was variable in 12 cases of rheumatoid arthritis, but Cy A initially diminished and later enhanced immunoglobulin production in all cases, suggesting a defect in the normal early response to EB virus in vitro.

Adolescent↗
PubMed1983

Lymphocyte enzyme activities in immunodeficiency syndromes with particular reference to common variable hypogammaglobulinaemia.

Circulating non-T lymphocytes had higher activities of 5'nucleotidase (plasma membrane), neutral alpha-glucosidase (endoplasmic reticulum) and basal leucine amino-peptidase than did T lymphocytes. Activities of catalase (peroxisomes), malate dehydrogenase (mitochondria), lactate dehydrogenase (cytosol) and N-acetyl-beta-glucosaminidase, beta-glucuronidase and acid phosphatase (lysosomes), were similar in the lymphocyte subfractions. Lymphocyte 5'nucleotidase (plasma membrane) in patients with common variable hypogammaglobulinaemia is much lower than normal. However, the decrease is less marked in X-linked hypogammaglobulinaemia, chronic lymphatic leukaemia or protein loosing enteropathy or in lymphocytes isolated from cord blood. Cells from patients with nephrotic syndrome had normal levels of 5'nucleotidase. Other plasma membrane marker enzymes (gamma-glutamyl transferase, leucine amino-peptidase) were normal in lymphocytes from patients with common variable hypogammaglobulinaemia. There is a selective reduction of mitochondrial (malate dehydrogenase) and cytosolic (lactate dehydrogenase) enzymes, with normal activities of lysosomal, peroxisomal and endoplasmic reticulum enzymes, in patients with common variable hypogammaglobulinaemia. The lymphocyte subcellular organelles in normal subjects and patients with common variable hypogammaglobulinaemia have similar properties on sucrose density gradient centrifugation. It is suggested that lymphocytes from patients with common variable hypogammaglobulinaemia show a specific enzymopathy and that this is not simply a reflection of cellular immaturity.

5'-Nucleotidase↗
PubMed1982

A radioimmunoassay for antibody to pneumococcal polysaccharides.

A radioimmunoassay for type specific pneumococcal polysaccharides is described. This involves obtaining specific polysaccharides from culture supernatants by precipitation with ethanol saturated with potassium acetate, and then after further purification labelling the tyraminated polysaccharide with 125 iodine. The radioimmunoassay itself is a standard ammonium sulphate precipitation technique (Farr assay) using IgG myeloma protein as a carrier. We have found that measuring antibodies after test immunization with a polyvalent pneumococcal vaccine is a useful aid in diagnosing functional antibody deficiency.

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

An analysis of the lymphocytotoxic activity found in sera from patients with hypogammaglobulinaemia.

Sera from 59 patients with hypogammaglobulinaemia (hypogamma) were assessed for lymphocytotoxic activity. The activity was compared with that found in sera from patients with systemic lupus erythematosus (SLE) in titre, class of antibody, target cell, and complement requirements. Sera from patients with hypogamma showed cytotoxic activity when compared with sera from normal donors; however, the activity was far less than that in sera from SLE patients, The cytotoxic titre of both hypogamma and SLE sera was greater against T cells than non-T cells. Sera showing activity could be used to sensitize lymphocytes and render them susceptible to subsequent lysis, but IgM was not detectable on the surface of the sensitized cells. Following sucrose density gradient fractionation of the sera the lymphocytotoxic activity was recovered in those fractions that contained IgM. Lymphocytotoxic activity was dependent on classical complement pathway activity. In all the experiments the hypogamma sera showed the same pattern of activity as the SLE sera, but the activity was always far weaker than that found in SLE sera. The evidence does not suggest that lymphocytotoxicity is likely to be more important in the pathogenesis of hypogamma.

Agammaglobulinemia↗
PubMed1982

Chronic cystitis and urethritis associated with ureaplasmal and mycoplasmal infection in primary hypogammaglobulinaemia.

Six of 58 patients with primary hypogammaglobulinaemia developed chronic urethritis and/or cystitis. We have some evidence that this complication may be caused by infection with strains Rof Ureaplasma urealyticum. This is important because ureaplasmas are usually resistant to most antibiotics routinely used to treat lower urinary tract infections. It appears that hypogammaglobulinaemic patients develop less localised and more severe ureaplasmal infections than immunocompetent subjects, which indicates that antibodies are important in controlling the growth of these organisms in the bladder and urethra.

Adult↗
PubMed1982

Studies on the kinetic properties and subcellular localization of adenine nucleotide phosphatases in peripheral blood lymphocytes from control subjects and patients with common variable primary hypogammaglobulinaemia.

Specific assays for 5'-nucleotidase, adenosine diphosphatase (ADPase) and Mg2+-dependent adenosine triphosphatase (Mg2+-ATPase) have been optimized for human lymphocytes and their subcellular localizations determined by sucrose density gradient centrifugation. 5'-Nucleotidase was localized solely to the plasma membrane of the lymphocyte. ADPase activity has been shown to have a dual localization to the plasma membrane and mitochondria, whilst Mg2+-ATPase was mainly located in the mitochondria. No [Na+,K+] activated Mg2+-dependent ATPase could be measured in these cells. We have confirmed the striking decrease in the specific activity of 5'-nucleotidase activity in lymphocytes from patients with common variable primary hypogammaglobulinaemia. In contrast, the specific activities of ADPase and Mg2+-ATPase showed no alteration in lymphocytes from the patient group when compared to controls. Thus the deficiency of ecto-5'-nucleotidase in the lymphocytes of patients with hypogammaglobulinaemia is a highly selective defect in purine metabolism.

5'-Nucleotidase↗
PubMed1982

Metabolic defects in immunodeficiency diseases.

There are two ways to find the cause of primary immunodeficiency diseases. One approach is to start with the immune defect and work backwards, using in vitro techniques to define where the primary abnormality lies in the immune response. Immunologists favour this approach for obvious reasons; and it is not without virtue since, for example, it has shown that the defect in most cases of primary hypogammaglobulinaemia is due to a failure of B lymphocyte maturation. The alternative approach is to screen empirically for defects in biochemical pathways in the hope of finding a clue which will eventually lead to the underlying disorder. This is a sensible approach in diseases which are clearly inherited (e.g. X-linked hypogammaglobulinaemia) but is less attractive in a disease such as late onset hypogammaglobulinaemia which is not obviously inherited. In practice, such procedures involve screening the urine for abnormalities in the quality or quantity of excreted compounds. Another way is to screen for abnormalities in organelle integrity by measuring the activity of various enzymes in subcellular fractions. In reality, the clue to the metabolic defect is usually discovered by accident, the prime example in our field being the discovery of adenosine deaminase (ADA) deficiency.

5'-Nucleotidase↗
PubMed1982

Effects of deoxyadenosine on the activation of ADA inhibited T & B cells.

Using an in vitro model of adenosine deaminase deficiency, we have shown that the triggering of T lymphocyte proliferation by PHA is inhibited by concentrations of deoxyadenosine likely to occur in the plasma of ADA deficient children with severe combined immunodeficiency (ADA-SCID). Prostaglandin E1 increases the sensitivity of T cells to this inhibition, suggesting that derangement of cyclic nucleotide metabolism underlies the profound T lymphopaenia seen in ADA-SCID and in patients treated with the ADA inhibitor, deoxycoformycin. The proliferation and Ig synthesis of ADA inhibited B cells stimulated with protein A and EBV is in general less sensitive to the inhibitory effects of deoxyadenosine. However, this sensitivity varies widely between experiments suggesting that other cells present in the cultures may modify the inhibitory effect of deoxyadenosine. This may help explain the variability in B cell numbers and function in patients with ADA-SCID.

Adenosine Deaminase↗
PubMed1982

Pre-B cell suppression by thymoma patient lymphocytes.

T lymphocytes from the blood of two thymoma patients with hypogammaglobulinaemia suppressed the in vitro proliferation of allogeneic pre-B cells. Both patients lacked pre-B and B cells in blood and bone marrow. It is possible that pre-B cells, as well as B cells, may be targets for suppression by T cells in thymoma patients with hypogammaglobulinaemia.

Adult↗