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Biomedical subjects

R J Levinsky

Publications and source records attributed to R J Levinsky.

At least 127 records · Page 7Linked to original sources
PubMed1985

Differences in surface antigen expression of human fibroblasts cultured from bone marrow compared with those obtained from skin and embryo lung tissue.

We have described the optimal conditions for the culture of human fibroblast cells from whole bone marrow aspirates and have shown that these fibroblasts differ in surface markers from those obtained from the skin and embryo lung tissue. All three fibroblast types express HLA class 1 antigens, together with an antigen found on T cells, granulocytes, white matter of brain and breast epithelial cells, but none of them expressed HLA class 2 antigens. In addition, skin fibroblasts expressed an antigen found on common acute lymphoblastic leukaemia cells, while bone marrow fibroblasts expressed an antigen found on human natural killer cells. Hence, all three types of fibroblasts can be separated on the basis of their surface markers, thereby suggesting a difference in maturation pathways.

Antigens, Surface↗
PubMed1984

Spontaneous remission of multi-system histiocytosis X.

Two infants presented with biopsy-proven histiocytosis X affecting multiple sites. Since neither showed evidence of organ failure or of constitutional upset, no specific therapy was given. In each case there was long-lasting spontaneous regression of disease. Analysis of blood mononuclear cells revealed a raised T4:T8 (helper:suppressor T lymphocyte) ratio at diagnosis but a normal ratio during remission. These observations support the argument that multi-system histiocytosis X, even in infants (Letterer-Siwe disease), is not a malignancy and that an "expectant" treatment policy may be indicated in selected patients.

Biopsy↗
PubMed1984

dATP accumulation and ATP depletion in platelets in adenosine deaminase deficiency: significance for the immune response?

High levels of dATP and dADP, accompanied by ATP depletion, were found in the platelets of two ADA-deficient children with severe combined immunodeficiency (SCID). In vitro studies demonstrated that even normal platelets had the ability to make dATP from deoxyadenosine (dAR) under physiological conditions. This capability was greatly enhanced by conditions simulating ADA deficiency. These results question whether the platelet has a specific role in the normal immune response.

Adenosine Deaminase↗
PubMed1984

Prenatal diagnosis of three cases of severe combined immunodeficiency: severe T cell deficiency during the first half of gestation in fetuses with adenosine deaminase deficiency.

The prenatal diagnosis of severe combined immunodeficiency (SCID) was made in three fetuses by staining fetal blood obtained at fetoscopy with a panel of monoclonal antibodies. There were less than 100 T cells/mm3 of fetal blood in these three cases compared to 2,500/mm3 in 14 immunologically normal fetuses. Cells bearing the cortical thymocyte antigen (NA1/34) were not detected in any of the normal or affected fetal blood samples. Two of the affected fetuses were also homozygous for a deficiency of adenosine deaminase (ADA) with undetectable levels of red cell ADA. All three affected fetuses were aborted and postmortem tissue was obtained in two cases. In both of these cases the thymus was markedly hypoplastic and contained no lymphoid cells. One of these fetuses was homozygous for ADA deficiency and the virtual absence of T cells or thymocytes during the second trimester of pregnancy indicates that placental access to the maternal circulation does not prevent damage to the T lineage stem cells in this disease. Prenatal diagnosis of SCID has previously only been possible in patients with a defined metabolic defect such as ADA deficiency, but these studies indicate that prenatal diagnosis now may be offered for most at risk pregnancies.

Adenosine Deaminase↗
PubMed1983

Successful bone-marrow transplantation for reticular dysgenesis.

A male infant with reticular dysgenesis received a bone-marrow transplant from his HLA-identical brother. Severe graft-versus-host disease developed but he responded to high-dose methylprednisolone. 3 years after grafting, the child is thriving with full haematological reconstitution and normal cell-mediated and humoral immunity. This is the first report of the survival beyond 17 weeks of a child with reticular dysgenesis.

Acute Disease↗
PubMed1983

Allogeneic bone-marrow transplantation in infantile malignant osteopetrosis.

Two infants with malignant osteopetrosis were treated by allogeneic bone-marrow transplantation after marrow ablation with busulphan and cyclophosphamide. Engraftment without graft-vs-host disease occurred in both cases. The first child established stable chimerism and is clinically well 30 months after receiving a histocompatible sibling bone-marrow graft: haematological, radiological, and biochemical features of osteopetrosis have completely resolved. The second child was non-identical with the marrow donor (his older sister) at a single HLA-B locus and received cyclosporin A as prophylaxis for graft-vs-host disease. 11 months after transplantation haematological abnormalities have resolved and radiological features have improved. The findings indicate that allogeneic bone-marrow transplantation should be considered the treatment of choice for infants with severe osteopetrosis who have histocompatible siblings.

Blood Grouping and Crossmatching↗
PubMed1983

Importance of platelet-free preparations for evaluating lymphocyte nucleotide levels in inherited or acquired immunodeficiency syndromes.

Low ATP/ADP ratios have been reported consistently for nucleotide levels of mononuclear cells separated from peripheral blood by conventional techniques. We have established that these low values (mean 2.3:1) were not due to cell damage or poor viability, but resulted from heavy platelet contamination, which is unavoidable when heparinized blood is used. The results reflect the low ATP/ADP ratios (mean 1.6:1) characteristic of platelets. Platelet-free extracts from defibrinated blood had very high ATP/ADP ratios (mean 17.4:1). The initial finding of detectable amounts of deoxy-ATP and deoxy-GTP in mononuclear cells from children with two distinct inherited immunodeficiency disorders [adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiency respectively] many have been due to contamination by nucleated erythrocytes as well as platelets in non-defibrinated preparations. Defibrination before nucleotide extraction of mononuclear cells from a patient with T-cell leukaemic/lymphoma treated with the ADA inhibitor deoxycoformycin enabled the demonstration of grossly raised deoxy-ATP levels relative to deoxy-ADP levels (ratio 16.1:1), associated with severe ATP depletion. This reciprocal relationship between ATP and dATP was found by us previously in the erythrocytes in inherited ADA deficiency. These findings underline the importance of extracts uncontaminated by platelets, or nucleated erythrocytes, in the evaluation of lymphocyte nucleotide levels in inherited or acquired immunodeficiency syndromes.

Adenosine Deaminase↗
PubMed1983

Differences between normal and milk allergic subjects in their immune responses after milk ingestion.

In order to understand why non-atopic people do not have adverse symptoms to food antigens which enter the circulation after eating, 8 non-atopic and 10 atopic eczema- and milk-allergic subjects were challenged with milk, and the types of circulating immune complexes formed were analysed. Although the amount of beta-lactoglobulin incorporated into complexes did not differ statistically between the groups, the type of immune complex did. Of the non-atopic individuals, 5 formed IgA and 2 IgG complexes. Of the milk-allergic group, all showed a rise in at least one type; 5 formed IgA, 7 IgG, 6 IgE, and 6 formed C1q-binding complexes. Our data suggest that serum IgA is concerned in safe food antigen handling in non-atopic people, and that the differences in the type of immune complexes formed in response to antigen challenge may underlie the systemic symptoms of food allergy.

Adolescent↗
PubMed1983

Lymphocyte subpopulations in primary immunodeficiency disorders.

Venous blood mononuclear cells from 42 children with primary immunodeficiency disorders and from controls matched for age were studied for lymphocyte subpopulations by E rosetting, surface immunoglobulin, and a panel of anti T cell monoclonal antibodies (OKT series). In 3 cases of severe combined immunodeficiency (SCID) due to adenosine deaminase deficiency, very few circulating T or B cells were found. The other 7 cases of SCID all had normal or, in 3 cases, very high numbers of circulating B cells, but in 6 of these very few cells showed T cell markers. One child had very high numbers of B cells and T cells with an immature pattern of reactivity similar to that found on common thymocytes. In T cell deficient children no consistent pattern was found, but in those with cartilage hair hypoplasia with immunodeficiency there was a low helper (OKT4) to suppressor (OKT8) ratio and high numbers of circulating OKT10 positive cells. In cases of X-linked agammaglobulinaemia circulating B cells were not found but the pattern of T cell markers was normal. In cases of common variable hypogammaglobulinaemia there was a wide scatter of helper (OKT4) to suppressor (OKT8) cell ratios. Five children were studied before and after treatment with the synthetic thymic hormone preparation TP5. There were appreciable alterations in the pattern of staining with anti T cell monoclonal antibodies in 4 of these cases, but in 1 case only was this accompanied by improvements in clinical and immune function.

Agammaglobulinemia↗