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Biomedical subjects

J W Stoop

Publications and source records attributed to J W Stoop.

At least 37 records · Page 2Linked to original sources
PubMed1985

Heterogeneity of immune defects in three children with a chronic active Epstein-Barr virus infection.

Three children, all girls, showed long-lasting clinical and serologic evidence of chronic active Epstein-Barr virus (EBV) infection. Extremely high serum titers of IgG- and IgA-type VCA antibodies and EA antibodies were present, whereas EBNA antibody titers were in the range of those found in seropositive individuals. All three patients repeatedly showed the presence of nonspecific pokeweed mitogen (PWM)-activatable suppressor cells in the peripheral blood. The analysis of EBV-specific cytotoxic T cells showed that one patient exhibited normal cytotoxicity, whereas a second patient demonstrated no EBV-specific cytotoxicity together with unusually high levels of virus-infected B cells in the blood and lymph node. The third patient repeatedly showed refractoriness of the circulating B cells to EBV infection, probably on the basis of some developmental defect. It was concluded that each patient has his or her own peculiar defect in the virus-host balance, indicating that heterogeneity may underlie the syndrome of chronic active EBV infection in humans.

Adolescent↗
PubMed1984

The effect of deoxyguanosine on human lymphocyte function. I. Analysis of the interference with lymphocyte proliferation in vitro.

The effect of deoxyguanosine on mitogen- and antigen-induced proliferation of peripheral blood lymphocytes from healthy donors was studied. Deoxyguanosine was found to inhibit the proliferative response to mitogens and antigens. Concentrations of deoxyguanosine causing 50% inhibition of the proliferation proved to be dependent on the activity of catabolic enzymes, such as purine nucleoside phosphorylase (PNP), in sera used in the culture media. The inhibitory effect of deoxyguanosine on phytohemagglutinin (PHA)-induced cell proliferation was prevented by deoxycytidine as well as by hypoxanthine. These findings were analyzed further by determination of intracellular (deoxy)-nucleotide levels. Stimulation of lymphocytes by PHA in the presence of deoxyguanosine leads to intracellular accumulation of dGTP. The presence of hypoxanthine in addition to deoxyguanosine abolished the inhibitory effect but did not prevent dGTP accumulation. On the other hand, the addition of deoxycytidine in combination with deoxyguanosine did not lead to intracellular accumulation of detectable amounts of dGTP, but only gave partial protection against the toxic effect. Furthermore, guanosine inhibited mitogen-induced cell proliferation to the same extent as did deoxyguanosine provided that the culture media were supplemented with pretreated fetal calf serum. Peripheral blood lymphocytes of a PNP-deficient or a HGPRT-deficient patient in cultures stimulated with PHA or pokeweed mitogen were resistant to the inhibitory effects of guanosine and were less sensitive to deoxyguanosine than cells of normal donors. The present results clearly show the involvement of two pathways contributing to deoxyguanosine-mediated inhibition of the proliferation of normal lymphocytes, i.e., on the one hand degradation of deoxyguanosine by PNP, salvage of guanine by HGPRT, and (possibly) phosphorylation of GMP eventually leading to GTP, and on the other hand formation of dGTP by direct phosphorylation of deoxyguanosine by deoxycytidine kinase.

Deoxycytidine↗
PubMed1984

The effect of deoxyguanosine on human lymphocyte function. II. Analysis of the interference with B lymphocyte differentiation in vitro.

The differentiation of normal human peripheral blood B lymphocytes into plasma cells in vitro, studied in mononuclear cells stimulated with PWM or in purified B cells stimulated with a T cell-replacing factor (TRF), can be inhibited by both deoxyguanosine (dGuo) and guanosine. The mechanism underlying this effect, which differs from the in vivo findings in PNP deficiency, was analyzed. dGuo toxicity can be antagonized by hypoxanthine but not by deoxycytidine. PNP-deficient and HGPRT-deficient B lymphocytes are not sensitive to the intoxicating properties of (deoxy)guanosine. Inhibition of PNP activity in normal B lymphocytes by 8-aminoguanosine decreases the sensitivity for dGuo intoxication. Incubation of purified B cells (stimulated with TRF) with dGuo leads to increased intracellular levels of guanosine di- and triphosphate (GDP and GTP), whereas deoxyguanosine triphosphate (dGTP) levels remain low. These observations lead to the conclusion that inhibition of B lymphocyte differentiation by dGuo is brought about by one of the end products of the pathway starting with degradation of dGuo by PNP, followed by guanine salvage by HGPRT, and possibly further phosphorylation of GMP into GDP and GTP. According to this mechanism, B lymphocyte differentiation in PNP deficiency is not sensitive to (deoxy)guanosine; because of the absence of PNP activity, these cells cannot accumulate GMP, GDP, and GTP, and therefore escape dGuo intoxication.

B-Lymphocytes↗
PubMed1983

Therapy in adenosine deaminase and purine nucleoside phosphorylase deficient patients.

The discovery of the causal association of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiency with some forms of primary immunodeficiency disease had led to new approaches to therapy, such as enzyme replacement. In ADA deficiency, bone marrow transplantation remains the primary method of choice. If no suitable bone marrow donor is available, enzyme replacement with irradiated erythrocyte transfusions should be considered. The latter therapy may be sustained by treatment with thymic factors. In ADA deficiency, bone marrow transplantation and, in about 50% of the cases, also enzyme replacement, may result in clinical and neurological improvement with concurrent (partial) restoration of immune function and (partial) disappearance of the metabolic abnormalities present before treatment. In PNP deficiency, enzyme replacement has been evaluated carefully in only two patients. The results disclose profound changes in the purine excretion patterns after each transfusion, and a slow but partial restoration of in vitro T cell function. Treatment of ADA and PNP deficiency with continued enzyme replacement by erythrocyte transfusions has certain risks which hopefully can be overcome in the near future by loading the patient's own blood cells with the missing enzyme.

Adenosine Deaminase↗
PubMed1983

Adolescents with cystic fibrosis in The Netherlands.

In a survey-study of all living Dutch patients with cystic fibrosis (CF) born before 1971 data have been gathered on sex, age, age at diagnosis; height and weight; treatment and social development. The group consists of 102 schoolchildren (8-11 years), 179 adolescents (12-21 years) and 28 young adults (22-40 years). Males are in the majority, especially in the 12 to 17 age group (61%). In 51% of all patients CF was diagnosed before the age of 2, and in 75% before the age of 5. Male CF patients are on average 6 cm (0.84 SD) shorter than normal and female patients 3 cm (0.48 SD). As far as weight for height is concerned, 54% of the CF patients fall below the 10th percentile. Weight for height is slightly lower in females than in males. CF patients usually leave primary school at an older age than their healthy peers. In comparison to healthy adolescents of the same age, adolescents with CF attend full-time day-school for a longer time, more of them receive general education and fewer take vocational training. Adolescents and young adults with CF do not stay longer than normal in the protective environment of their parental home.

Adolescent↗
PubMed1983

Inherited deficiency of the third component of complement associated with recurrent pyogenic infections, circulating immune complexes, and vasculitis in a Dutch family.

A family is described in which 3/11 children showed a homozygous deficiency of C3, and both parents and six other children had subnormal levels of C3. The three children with selective C3 deficiency suffered repeatedly from bacterial infections, whereas the parents and the other siblings were clinically healthy. During infectious episodes the patients showed a maculopapular skin rash, and at such times immune complexes were present in the serum. Biopsy specimens of the skin lesions showed the picture of leukocytoclastic vasculitis.

Adolescent↗
PubMed1980

The serum IgG subclass levels in healthy infants of 13--62 weeks of age.

The levels of IgG1, IgG2, IgG3, and IgG4 were determined in serum samples of 160 infants aged 13--62 weeks, and of their mothers. In addition the serum IgM, IgG, IgA, and IgD levels of the infants are presented. The results show that IgM, IgG1, and IgG3 slightly increase during the first year of life, whereas IgG2, IgG4, IgA, and IgD hardly do. This difference in the development of the various immunoglobulin isotypes reflects differences in the terminal maturation of subsets of B-lymphocytes into plasma cells. About 50% of the infants of this age had no detectable IgG4 and three children had no IgG2. These observations indicate that longitudinal investigations are needed in children suspected of a IgG2 or IgG4 subclass deficiency. No statistically significant influence of sex on the IgG subclasses could be demonstrated in these infants.

Adolescent↗
PubMed1980

Lymphocyte subpopulations in patients with various immunodeficiencies.

We have studied patients with various immunodeficiencies for the occurrence of blood lymphocytes bearing six different surface markers: the affinity to sheep erythrocytes (Es) to identify T cells, the presence of surface-bound immunoglobulins (sIg) to distinguish B cells, the affinity to mouse erythrocytes (Em) as a second B cell marker, and the receptors for the Fc part of IgM (IgM-FcR), the Fc part of IgG (IgG-FcR) and for complement (CR). IgG-FcR bearing lymphocytes were present in normal proportions and the same was found for CR-positive lymphocytes. None of the patients with congenital agammaglobulinaemia had sIg-bearing or Em-binding B lymphocytes. Four patients with ataxia teleangiectasia had low B cells and 3 out of 4 also had low proportions of IgM-FcR-bearing (T) cells. A child with partial DiGeorge syndrome did not have a grossly abnormal marker pattern although there appeared to be a shift in the T/B cell ratio in favour of the B cells. In a patient with selective cellular immunodeficiency associated with a purine nucleoside phosphorylase deficiency, who was followed during reconstitution therapy with plasma and red cells, a positive change in the marker pattern was seen. Similar observations were made in a child with combined immunodeficiency during treatment. The findings are being discussed in the light of the current knowledge of the functions and ontogeny of lymphocyte subsets.

Adolescent↗
PubMed1980

Erythrocyte metabolism in purine nucleoside phosphorylase deficiency after enzyme replacement therapy by infusion of erythrocytes.

Purine nucleoside phosphorylase deficiency is associated with a severely defective T-cell immunity. A patient with purine nucleoside phosphorylase deficiency was treated with transfusions of irradiated erythrocytes and plasma. This resulted in a remarkable correction of the metabolic disturbances in the patient. The urinary excretion of inosine, deoxyinosine, guanosine, and deoxyguanosine decreased, whereas uric acid excretion as well as serum uric acid concentration increased. It could be shown that the enzyme activity of the circulating erythrocytes correlated inversely with the urinary excretion of nucleosides and directly with the excretion of uric acid. As a consequence of the therapy, several glycolytic intermediates of the erythrocytes were increased, especially 2,3-diphosphoglycerate. The high 2,3-diphosphoglycerate level caused a shift to the right of the oxygen dissociation curve (P50 = 32.9 mm Hg). The immunological status of the patient showed definite improvement after the enzyme replacement therapy.

Blood Transfusion↗
PubMed1980

Phagocytic and chemotactic function of polymorphonuclear and mononuclear leucocytes in patients with recurrent staphylococcal infections.

From 21 patients with chronic or recurrent staphylococcal infections, phagocytosis and intracellular killing of Staphylococcus aureus by polymorphonuclear (PMN) and mononuclear (MN) leucocytes were evaluated. Also chemotactic responsiveness and the capacity of their sera to opsonize Staph. aureus was tested. The chemotactic, phagocytic and bactericidal capacity of PMN's and MN's from patients was significantly decreased. The mean uptake of Staph. aureus by patient PMN's and MN's was 65% and 44%, respectively, as compared to 85% and 75% observed with PMN's and MN's from 38 healthy donors. The phagocytic activity of 17/21 patients (81%) was below the normal range. A decreased chemotactic mobility and bactericidal capacity of patient leukocytes was also found and was always accompanied by a decreased rate of ingestion. Although a great variability was noted in the phagocytic capacity of leucocytes from patients tested repeatedly over periods up to 82 weeks, the mean value for phagocytosis remained below the normal range in 10/11 patients included in the follow-up study. Except for 1 patient with dysgammaglobulinemia, sera from the patients contained normal amounts of immunoglobulins and complement (CH50 and C3), and they all effectively opsonized Staph. aureus. The results indicate that defects in leucocyte function may be frequently involved in the pathogenesis of recurrent Staph. aureus infections.

Adolescent↗
PubMed1979

Urinary excretion of orotic acid, orotidine and other pyrimidines in a patient with purine nucleoside phosphorylase deficiency.

Urinary orotidine and orotic acid have been determined in a patient with purine nucleoside phosphorylase (PNP) deficiency under various dietary therapeutic conditions. For this purpose a new procedure for the analysis of both compounds has been developed, consisting of prefractionation with Dowex 1X8, followed by two HPLC steps on a micro Bondapak NH2 and a micro Bondapak C18 column. With this method normal as well as slightly elevated excretions of orotic acid have been found in our patient. No evidence was obtained for inhibition of OPRT by purine (deoxy)nucleosides as a cause of pyrimidine starvation. A significant increase of urinary orotidine was found after loading with allopurinol. For comparison excretory values in a patient with ornithine transcarbamylase deficiency and also in a patient with orotic aciduria type I are shown. The possible cause of the slight increase in urinary orotic acid in our patient has been discussed.

Allopurinol↗
PubMed1979

Congenital ichthyosis: concurrent immunodeficiency and atypical T cells.

A patient with congenital ichthyosis and progressive neurologic anomalies showed disturbances in the specific humoral and cellular defense as well as the presence of atypical lymphoid cells in skin and lymph node. The latter resembled the atypical T cells found in mycosis fungoides and Sézary syndrome. The possibility of the presence of either a cutaneous T cell lymphoma or unregulated T cell stimulation leading to concurrent immunodeficiency in this patient is discussed.

Decerebrate State↗