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Biomedical subjects

R J Levinsky

Publications and source records attributed to R J Levinsky.

At least 145 records · Page 8Linked to original sources
PubMed1983

Phorbol myristate acetate stimulated NBT test: a simple method suitable for antenatal diagnosis of chronic granulomatous disease.

When endotoxin was compared with phorbol myristate acetate (PMA) for stimulation of phagocytes in the nitroblue tetrazolium (NBT) test, both methods discriminated between affected patients with X-linked chronic granulomatous disease (CGD) and controls, but only the PMA NBT test distinguished female carriers of CGD. Endotoxin provided no stimulation of normal fetal blood whereas PMA was an effective stimulator. Our results indicate the superiority of the PMA NBT test for diagnosis of patients and carriers of CGD and should allow accurate antenatal diagnosis of the disease.

Adolescent↗
PubMed1983

Impaired production of interleukins in patients with cell-mediated immunodeficiencies.

The poor mitogen response to phytohaemagglutinin (PHA) of lymphocytes from three patients with cell-mediated immunodeficiencies was restored to normal when supernatants containing interleukin 2 (IL-2) were added. One of three children with severe combined immunodeficiency also showed a partial response. There was no improvement in the normal mitogenic response of the lymphocytes from patients with either the X linked or common variable forms of hypogammaglobulinaemia. All three patients with cell-mediated immunodeficiencies showed gross imbalance in the ratio of helper/inducer (OKT4+) to suppressor/cytotoxic (OKT8+) T cells. The PHA stimulated culture supernatant from one of these patients failed to induce proliferation of a cytolytic continuous T cell line. Our data suggests that the underlying defect in these patients may be a failure in production of interleukins but not in the acquisition of IL-2 receptors.

Adult↗
PubMed1983

Intestinal antigen handling at mucosal surfaces in health and disease: human and experimental studies.

Intestinal uptake of antigenically intact food proteins was measured by a solid phase radioimmunoassay on serum samples after instillation of food proteins into a closed intestinal loop of adult Wistar rats. Compared to normal controls, rats fed protein deficient diets during five months had a higher macromolecular uptake. During the course of Nippostrongylus brasiliensis infection this uptake was decreased. In cholera toxin induced secretory states of the intestinal mucosa uptake of food proteins was increased. In human studies the uptake of Beta-Lactoglobulin after a milk meal was shown to be increased in premature compared to full-term neonates. In children suffering from intestinal helminth infection the macromolecular uptake was higher before treatment compared to that after treatment. These studies show that various pathological situations can alter the antigen handling at mucosal surfaces.

Adolescent↗
PubMed1982

Reciprocal relationship between erythrocyte ATP and deoxy-ATP levels in inherited ADA deficiency.

A reciprocal relationship between erythrocyte ATP and deoxy-ATP levels has been noted in an immunodeficient child with adenosine deaminase (ADA) deficiency during therapy with red cell transfusions. The sum of red cell ATP plus deoxy-ATP equalled the normal complement of ATP prior to any form of therapy. dATP, dADP and dAMP levels were found in the same ratio (10:1:0.1) as the adenine nucleotides ATP, ADP and AMP. Red cell ATP levels were low, not high or normal as found by others in ADA deficiency, but no deoxyadenosine nucleotides could be found in peripheral blood mononuclear cells. Erythrocyte ATP depletion has recently been identified as a serious consequence of anti-leukaemic therapy with ADA inhibitors; it may thus be an important but hitherto unrecognised contributing factor in the clinical expression of inherited ADA deficiency.

Adenosine↗
PubMed1982

Phenotypic analysis of fetal blood leucocytes: potential for prenatal diagnosis of immunodeficiency disorders.

Recent technological advances allow the detection and quantitation of subsets of leucocytes using monoclonal antibodies. We have taken advantage of this to study the ontogeny of fetal blood leucocytes, using very small blood samples obtained at fetoscopy. By 14 weeks gestation T cells represent 35 per cent or more of fetal leucocytes and the distribution of the helper/inducer and suppressor/cytotoxic subsets is similar to that of adults. B lymphocytes before 16 1/2 weeks are low (4-20 per cent), but rise to a mean of 28 per cent in 17-26 week fetuses. Granulocytic cells, many of which are phenotypically immature, represent 18-34 per cent of total leucocytes. The methodology employed is very reliable and offers the opportunity for the prenatal diagnosis of some immunodeficiency disorders, since using the same reagents we have diagnosed children with severe combined immunodeficiency shortly after birth.

Antibodies, Monoclonal↗
PubMed1982

Formation and degradation of deoxyadenosine nucleotides in inherited adenosine deaminase deficiency.

dATP, dADP, and dAMP equalled or exceeded the depleted levels of ATP, ADP, and AMP in erythrocytes from two children with adenosine deaminase (ADA; EC 3.5.4.4) deficiency. dATP and dADP were identified in the mononuclear cells of only one child. The levels of deoxyadenosine compounds fell dramatically after enzyme replacement therapy and were no longer detectable in the urine or in mononuclear cells. Erythrocyte adenosine nucleotide levels showed a corresponding increase. Intact erythrocytes prior to treatment contained adenine, presumed to be from deoxyadenosine degraded during extraction. Adenosine at high concentrations in vitro increased both dATP and ATP levels and decreased intracellular deoxyadenosine levels. There was no significant deamination of either [8-14C]adenosine or deoxyadenosine by intact ADA-deficient erythrocytes. About 90% of adenosine was metabolized to ATP at substrate concentrations from 10-100 microM, compared to 40-60% of deoxyadenosine metabolized to dATP. These studies suggest that (i) high intracellular deoxyadenosine levels may be necessary in vivo to sustain the raised dATP levels in ADA deficiency. (ii) When ADA is inhibited or absent, deoxyadenosine is removed rapidly from the circulation by the human erythrocyte utilizing an adenosine transport system linked to both ADA and adenosine kinase (EC 2.7.1.20).

Adenosine↗
PubMed1982

Milk antigen absorption in the preterm and term neonate.

The concentrations of beta-lactoglobulin was measured in the sera of 47 preterm an term neonates during the first few days of life under standardised conditions after feeding with a cows' milk'based formula. Preterm neonates, particularly those of less than 33 weeks' gestation, had higher serum concentrations of beta-lactoglobulin than term neonates given an equivalent mild feed. Prior feeding with breast milk did not diminish the amount of beta-lactoglobulin absorbed. Our results suggest tha te ability of the gastrointestinal tract to exclude antigenically intact food proteins increases with gestational age and that gut closure occurs normally before birth in man.

Breast Feeding↗
PubMed1982

Intestinal absorption of food antigens in coeliac disease.

Serum concentrations of ovalbumin, beta-lactoglobulin, and antigen-antibody complexes were measured after jejunal administration of milk and raw egg in 6 children with active coeliac disease and in 4 controls. The results did not support the hypothesis of a generalised increase in absorption of antigens from the intestinal lumen in coeliac disease.

Antigen-Antibody Complex↗
PubMed1982

Circulating soluble immune complexes containing pseudomonas antigens in cystic fibrosis.

In order to investigate whether circulating immune complexes containing Pseudomonas aeruginosa antigens mediate pulmonary damage in cystic fibrosis, we studied lung function, serum immune complex levels, and immunoglobulin concentrations in relationship to chronic pseudomonas colonisation in 69 affected children. Sixteen of the children with cystic fibrosis had increased levels of immune complexes which contained pseudomonas antigens. There was no significant relationship between lung function corrected for the effect of chronic pseudomonas colonisation and the presence of such complexes or increased levels of complexes detected by Cl1 binding or raised serum immunoglobulin concentrations. Our results suggest that these abnormalities in cystic fibrosis are secondary effects of chronic infection and they do not provide evidence for immune complex mediated lung damage in this disease.

Adolescent↗
PubMed1982

Pseudomonas infection, allergy, and cystic fibrosis.

The clinical significance of the high prevalence of positive immediate skin tests in cystic fibrosis is unclear. Using analysis of variance, we have tested the hypothesis that patients with allergic cystic fibrosis have worse lung disease than non-allergic patients. Clinical data, skin prick tests, total or specific IgE antibody levels, chest radiographs, and pulmonary function tests were obtained in 104 cystic fibrosis patients. Patients with positive immediate skin reactions to at least one allergen were more likely to be persistently colonised by Pseudomonas aeruginosa than skin test negative patients. The skin test positive patients were also significantly older (mean difference 2.15 years). Analysis of variance showed that pseudomonas infection was the most significant factor contributing to lung damage and the effect of allergy was not significant. Similar longitudinal analysis of pulmonary function over 5 years and study of the hospital admission rate showed that the only statistically significant factor associated with deterioration was colonisation with P. aeruginosa.

Adolescent↗
PubMed1982

Treatment of cell-mediated immunodeficiency with calf thymic hormone (T.P.I.).

Eight children, four with combined immunodeficiencies and four with isolated T cell defects were treated with TPI, a crude calf thymic extract. Assessment of response was made on clinical grounds and by monitoring of immune function (T and B cell numbers, immunoglobulin levels, PHA response and delayed cutaneous reaction to Candida antigen). One child with severe combined immunodeficiency showed marked clinical improvement together with reconstitution of T cell numbers and, surprisingly, B cell numbers and immunoglobulin production. Two further children, one with a form of combined immunodeficiency and the other with a T cell defect and extensive cutaneous herpes simplex infection, showed benefit from therapy though in the latter we could not demonstrate that this was important in clearing the virus infection. None of the other children showed any consistent improvement either clinically or on testing. We found no evidence of toxicity, allergy or other adverse effects of therapy.

Animals↗
PubMed1982

Quantitative and functional deficit of suppressor T cells in children with atopic eczema.

Helper (OKT4+) and suppressor (OKT8+) T cells were enumerated in 16 children with severe atopic eczema. Compared to controls (median 1 . 8) the ratio of OKT4+/OKT8+ cells in the patients was significantly higher (median 2 . 65, P less than 0 . 002). Functional suppressor activity in these patients was assessed by concanavalin A (Con A) activation and suppression of pokeweed mitogen (PWM) induced immunoglobulin production by plasma cells and Con A proliferation of T cells. In both assays a lack of suppression was shown (Con A/PWM, P less than 0 . 02; Con A/Con A, P less than 0 . 05). There was a significant inverse correlation between the helper/suppressor ratio and functional suppressor activity (P less than 0 . 01). These results indicate that a defect of T cell regulation does exist in atopic eczema and if it is of primary pathogenic importance, immunotherapy to restore the balance may prove useful.

Adolescent↗
PubMed1982

Defective immune interferon production and natural killer activity associated with poor neutrophil mobility and delayed umbilical cord separation.

Two infants with recurrent infections and a history of delay in separation of the umbilical cord (1 month and 17 days) had severely impaired neutrophil mobility. In addition very poor natural killer cell (NK) activity of blood lymphocytes against a leukaemia cell line (Molt 4F) was found. Incubation of lymphocytes with lymphoblastoid interferon increased NK activity in the one case tested. No immune (gamma) interferon production was detected in Raji cell and phytohaemagglutinin (PHA) stimulated cultures from the other case. Apart from an abnormal dose-response curve in thymidine uptake after PHA stimulation of blood lymphocytes, no other abnormalities were found in a range of immunological tests. Ascorbic acid improved neutrophil mobility but had no effect, on NK activity. Both children have subsequently died from septicaemic illnesses.

Cells, Cultured↗