Search PubMed⌕ Search

Biomedical subjects

D E Joshua

Publications and source records attributed to D E Joshua.

At least 73 records · Page 4Linked to original sources

Automated enumeration of reticulocytes using acridine orange.

Manual methods of counting reticulocytes using supravital stains, such as new methylene blue, have long been recognized to be subject to technical errors. Automated reticulocyte enumeration has recently become available with the development of an automated cell flow-cytometer, the Ortho Spectrum III. In this method a fluorescent dye, acridine orange, which stains RNA in a manner similar to supravital stains, is used to distinguish reticulocytes from mature erythrocytes. We have evaluated this technique and found that it compares favourably with manual counting methods.

Acridine Orange↗

Monoclonal antibodies to human FVIIIR:Ag and FVIIIC.

A series of monoclonal antibodies have been produced which recognize different epitopes of the factor VIII molecule. The antibodies were raised in mice against high purity factor VIII (FVIII) and the mouse spleens used in cell fusion experiments. Following cell fusion the hybridoma supernatants were used for screening with a solid phase radioimmunoassay (RIA) technique. The antibodies detected were differentiated by their degree of attachment to 2 components of the FVIII molecule, FVIII related antigen (FVIIIR:Ag) (also called von Willebrand's Factor) and FVIII coagulant (FVIIIC). Immunofluorescence and immunoperoxidase studies both showed the FVIIIR:Ag antibodies to be localized to the endothelial cells of the blood vessel walls. They can, therefore, be used for histological identification of these cells on cryostat and paraffin sections. The anti-FVIIIR:Ag antibodies have no anticoagulant properties, whereas the anti-FVIIIC antibody reacts as an instant inhibitor with a strength of 35,000 new Oxford U/ml. These antibodies are stable reagents and suitable for radioimmunoassay for both FVIIIR:Ag and FVIIIC.

Animals↗

Monitoring myeloma: light chain isotype suppression. A new parameter.

Optimal therapy in patients with multiple myeloma relies on methods which indicate stability or progression of disease. At present, patients are assessed by monitoring the myeloma M-component in the serum and the urinary light chain excretion levels, or by calculating the myeloma cell mass. However, clinical disease activity does not always correlate with changes in these indices. Recent studies suggest that monitoring the expression of light chain isotypes on peripheral blood lymphocytes may provide evidence of progressive disease before clinical deterioration. Stable plateau phase disease has been shown to be associated with suppression of the expression, on peripheral blood lymphocytes, of the light chain isotype concordant with the malignant paraprotein. Loss of this suppression has been associated with active disease.

Antineoplastic Combined Chemotherapy Protocols↗

Light chain isotype associated suppression of surface immunoglobulin expression on peripheral blood lymphocytes in myeloma during plateau phase.

Light chain isotype suppression in multiple myeloma has been reported in the plasma cells of the lamina propria of the gut (Leonard et al, 1979). In this paper we present further evidence of systemic suppression of the light chain isotype of the paraprotein expressed on normal peripheral blood lymphocytes in myeloma. Twenty patients with myeloma in plateau phase were monitored over 6 months for the expression of either kappa or lambda light chains on the surface of peripheral blood lymphocytes using monoclonal antibodies. The surface markers were analysed on an Ortho Spectrum III flow cytometer. Results of these studies indicate a selective suppression of the cells expressing the light chain isotype of the paraprotein in stable myeloma. Thus, in kappa myeloma there is a low kappa/lambda ratio and in lambda myeloma there is a high kappa/lambda ratio, and this suppression is lost with progressive disease.

B-Lymphocytes↗

Abnormal T-cell subpopulations in hemophilic patients receiving factor VIII concentrates from voluntary donors.

Recently, Acquired Immune Deficiency Syndrome (AIDS) has been reported in hemophiliacs in the USA, Canada and Spain, and this has caused considerable concern amongst hemophiliacs regarding the use of factor VIII concentrates. The aim of this study was to determine whether hemophiliacs in Australia have T-lymphocyte subpopulation changes similar to those observed in patients with AIDS. Factor VIII produced in Australia is derived from a totally volunteer blood donor system and none of the hemophiliacs in this study had received commercial blood products. For the hemophiliacs, the T-helper cell to T-suppressor cell ratio was 1.1 +/- 0.6 (mean +/- SD) which was significantly less (p less than 0.001) than that of the normal age and sex-matched controls. There was a significant relative (p less than 0.001) and absolute (p less than 0.05) reduction of the helper cell subsets and a significant relative (p less than 0.001) and absolute (p less than 0.05) increase of the suppressor cell subsets, in the hemophiliacs compared to the normal controls. There appears to be no correlation between the amount of factor VIII therapy received during the last three years and the T-cell subset changes. All patients with Christmas disease had T-cell subsets within the normal range. All patients were negative for the hepatitis B virus antigen, but all were positive for the antibody, indicating that there had been exposure to the hepatitis virus in all cases. Cytomegalovirus titres were uniformly low and immunoglobulin levels were normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Chronic myeloid leukaemia presenting as femoral head necrosis.

A 17-year-old male whose initial presentation of chronic myeloid leukaemia (CML) was necrosis of the right femoral head is reported. This is the first case report to our knowledge of CML presenting with such a lesion and is of further interest in that almost all reported cases of destructive bony lesions in this disease have been associated with blast transformation. Our patient in contrast has remained in stable chronic phase for over 30 months.

Adolescent↗

Immunosuppression in BALB/c mice bearing the plasmacytoma TEPC-183: massive increase in red pulp macrophages induced by the tumour.

An increase was found in total macrophage numbers in the spleens of BALB/c mice bearing the plasmacytoma TEPC-183 compared with controls. The increase was shown to be confined to red pulp macrophage; white pulp macrophage numbers were normal as were the number of macrophages which took up hydroxyethyl starch. It is suggested that this increase in red pulp macrophages may account for the suppression of primary immune responses caused by spleen cells from TEPC-183 bearing mice. This effect may be due to increased numbers of normal macrophages rather than the generation of distinctive suppressor macrophages as suggested previously.

Animals↗

Immune suppression in BALB/c mice bearing the plasmacytoma TEPC-183: evidence for normal lymphocyte but defective macrophage function.

This paper analyses impairment of the primary immune response of mice bearing the plasmacytoma TEPC-183. Healthy animals and mice bearing the reported non-immunosuppressive tumour MOPC-104E were used as controls. The defect was shown to affect both primary IgG and IgM responses to chicken cells (CRBC) and to be related to tumour size. However, the primary immune depression could be overcome either by increasing the antigen dose or by using Freund's complete adjuvant together with antigen. Secondary responses were also depressed. This depression was more pronounced if the animals was primed after, rather than before, tumour implantation. Further studies involved the measurement of primary immune responses of immunologically deprived syngeneic mice, after they had been reconstituted with cells from normal or tumour-bearing mice. Lymphocyte reconstitution experiments were carried out in mice which had been irradiated with 950R. Various lymphoid preparations from TEPC-183-bearing mice were unable to bring about such restoration. It is concluded that the impairment of the primary immune response of mice bearing the plasmacytoma TEPC-183 is due to a macrophage, rather than a lymphocyte, abnormality. However, none of these transfer studies suggested that positive suppression of primary immune responses was being mediated by cells from TEPC-183-bearing mice.

Animals↗

Androgen-induced hepatoma.

Three cases of hepatocellular carcinoma are reported in young men who had been taking androgenic-anabolic steroids. The tumours were histologically similar to those described in previous reports. The tumour progressed slowly in two patients during four and seven years of observation, but in the latter bony metastases occurred. In two patients the tumours regressed after administration of the drug was discontinued. These cases strengthen the evidence that exogenous androgenic-anabolic steroids may produce liver tumours. The use of these drugs should be confined to serious conditions in which they are known to be effective. Biochemical tests of liver function and serum alphs-fetoprotein estimation are not useful as screening-tests for hepatoma in patients taking androgens, and regular isotopic liver-scanning is recommended.

Adult↗