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Biomedical subjects

J A Tooze

Publications and source records attributed to J A Tooze.

26 records · Page 2Linked to original sources

Expression of lacto-N-fucopentaose III (CD15)- and sialyl-Lewis X-bearing molecules and their functional properties in eosinophils from patients with the idiopathic hypereosinophilic syndrome.

As the carbohydrate lacto-N-fucopentaose III (CD15 antigen or X-determinant) and its sialylated derivative sialyl-Lewis X are involved in the adhesion of cells rolling along the surface of endothelial cells, experiments were done to study the presence of these molecules on human eosinophils from patients with the idiopathic hypereosinophilic syndrome. Normal-density eosinophils from some patients showed higher levels of expression for lacto-N-fucopentaose III than light-density eosinophils. In contrast, sialyl-Lewis X was highly expressed by light-density eosinophils. Activation of normal-density eosinophils with calcium ionophore A23187 resulted in increased expression of these molecules for a short time. Monoclonal antibodies to these carbohydrates stimulated eosinophils to secrete eosinophil cationic protein, but not eosinophil peroxidase, and acted as costimulatory signals for C3b-induced degranulation of eosinophil cationic protein. It was suggested that CD15 and sialyl-Lewis X might contribute to eosinophil-mediated tissue injury in patients with the idiopathic hypereosinophilic syndrome.

Adult↗

Response of aplastic anaemia and scleroderma to cyclosporin.

Scleroderma and aplastic anaemia (AA) occurred simultaneously in a patient. Treatment with antilymphocyte globulin (ALG) resulted in some improvement of the scleroderma and a partial, temporary response of the AA. Both the scleroderma and AA then responded dramatically to cyclosporin (CSA) therapy. Subsequently, a positive Ham's test, together with a reduction in the phosphatidyl-inositolglycan (PIG) anchored membrane proteins decay accelerating factor (DAF, CD55) and membrane inhibitor of reactive lysis (MIRL, CD59), confirmed a diagnosis of paroxysmal nocturnal haemoglobinuria (PNH) affecting erythroid, myeloid and lymphoid cell lineages. We hypothesize that the pathogenesis of the bone marrow failure in this patient was a stem cell defect with a secondary immune response involving T-lymphocytes that may have simultaneously triggered the pancytopenia and scleroderma.

Anemia, Aplastic↗

Characterization of human umbilical vein endothelial cell lines produced by transfection with the early region of SV40.

Human umbilical vein endothelial cells were transfected by electroporation with the plasmid pSV3neo, containing the early region of simian virus 40. The resultant "cell lines" divide rapidly (population doubling time of 33 h) for up to 24 passages in medium supplemented with 5% (v/v) serum and 2.5 micrograms/ml endothelial cell growth supplement. Several of these lines express basal levels of ICAM-1 and MHC class I but not MHC class II. One cell line, designated SGHEC-7, retained a number of differentiated endothelial cell functions throughout its lifespan. These functions include increased production of tissue plasminogen activator in response to histamine, thrombin, and PMA. Stability of function and rapid growth over 24 passages endow these cells with a number of advantages over primary cultures. The homogeneous cell population and consistency of response make them ideal for biochemical and immunological studies hereto impractical with primary human endothelial cells. The success of this approach may allow the production of functional cell lines from other vascular beds.

Cell Adhesion Molecules↗

Acquired aplastic anemia and paroxysmal nocturnal hemoglobinuria: studies on clonality.

We used X-chromosome methylation patterns to study clonality in aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH). AA is usually not considered to be a clonal stem cell disorder, although this has not been directly investigated. PNH is generally assumed to be a clonal disorder, although there is contradictory evidence. Methylation analysis was performed on DNA from separated granulocytes and mononuclear cells, using the M27 beta and hypoxanthine phosphoribosyl transferase (HPRT) probes. Six of seven AA patients showed a polyclonal pattern of X inactivation. In contrast, five of five PNH patients showed a monoclonal pattern. These results imply that at least 80% of the cell population derives from a single stem cell. Because this high proportion of PNH cells might be considered surprising, three patients were studied for membrane expression of decay accelerating factor (DAF). In support of the DNA data, more than 95% of the granulocytes were DAF--ve in all three cases. We conclude that AA is predominantly a polyclonal disorder, whereas PNH is a clonal stem cell disorder. Our data support a model in which a single PNH stem cell has a growth advantage over other remaining stem cells and eventually dominates hematopoiesis.

Adult↗

Decreased expression of complement receptor type 2 (CR2) on neoplastic B cells of chronic lymphocytic leukaemia.

Neoplastic cells from 49 patients with B cell chronic lymphocytic leukaemia (B-CLL) were studied and compared with normal peripheral and tonsillar B cells using CD21 monoclonal antibodies. Membrane expression of CR2 was quantified by calibrated flow cytometry and by binding analysis with radiolabelled antibody. Both assays indicate that B-CLL cells express only 30% of the CR2 found on normal B cells. These findings are further evidence of the aberrant phenotype of B-CLL cells.

Antibodies, Monoclonal↗