Search PubMed⌕ Search

Biomedical subjects

J Biggs

Publications and source records attributed to J Biggs.

At least 91 records · Page 5Linked to original sources
PubMed1984

Cyclosporin-associated central nervous system toxicity after allogeneic bone marrow transplantation.

Five of 64 recipients of HLA-identical sibling marrow allografts who were given cyclosporin (CSP) to minimize graft-versus-host disease posttransplant had a serious neurological illness thought to be due to CSP. Characteristic clinical features included a motor spinal cord syndrome, a cerebellar-like syndrome, and mental confusion. All five recovered when the CSP dose was reduced or the drug was stopped.

Acute Kidney Injury↗
PubMed1984

Distribution and concentration of cyclosporin in human blood.

In patients receiving cyclosporin to minimise graft versus host disease after allogeneic bone marrow transplantation, whole blood cyclosporin concentration was roughly twice the serum concentration when blood was separated at 37 degrees C. In turn, blood separation at 37 degrees C resulted in a doubling of serum cyclosporin concentration compared with separation at room temperature. In vitro studies showed that the latter phenomenon was due to a temperature dependent partitioning of cyclosporin between plasma and red cells, such that increased cyclosporin was taken up from the serum into red cells at room temperature. Increasing delay in separation of patient blood (at either temperature) resulted in a gradually increasing cyclosporin serum concentration. Further in vitro studies showed that a distribution equilibrium between blood components was reached within 30 min incubation. Red cell uptake of cyclosporin was saturable at an incubation concentration of greater than 4 microgram/ml, while plasma and mononuclear cells showed a linear uptake to 7 micrograms/ml. The cellular cyclosporin content of a mononuclear cell was roughly 1000 times greater than that of an erythrocyte. For clinical monitoring we recommend the measurement of cyclosporin concentration either in whole blood or in serum separated at 37 degrees C without delay after venepuncture.

Bone Marrow Transplantation↗
PubMed1984

Tissue distribution and toxicity of cyclosporin A in the mouse.

Groups of mice were given cyclosporin A (CyA) subcutaneously for 6 wk at a dose of 12.5, 50 or 200 mg/kg/d. After 7, 21 and 42 days of CyA administration the CyA content of serum, thymus, mesenteric lymph nodes, spleen, kidney, liver, lung, small and large intestine and brain was measured, each organ was examined histologically, and the total viable nucleated cell content of thymus, mesenteric lymph nodes, spleen and femoral marrow was analysed. CyA was detected in every organ assayed at each concentration of CyA administered. The mean concentration of CyA per organ was consistently highest in organs of mice given CyA 200 mg/kg/d and lowest in those given 12.5 mg/kg/d at each time point, but there was pronounced variability in the concentration of CyA between individual mice. Repeated administration of CyA after the first week did not further elevate CyA tissue concentrations. At doses of 50 or 200 mg/kg/d CyA caused weight loss, diarrhea, intussusception and fatal neurotoxicity. In addition, the spleen, thymus and mesenteric lymph nodes of mice given CyA 50 or 200 mg/kg/d were hypocellular and disorganized, and all lymphoid organs contained numerous pyknotic lymphocytes. The liver showed fatty change and the kidney degeneration of proximal tubules. Femoral marrow showed enlarged and congested sinuses. No abnormalities were noted in mice given CyA 12.5 mg/kg/d.

Animals↗
PubMed1983

Bone marrow transplantation in 33 patients with malignant blood diseases and severe aplastic anaemia.

Allogeneic bone marrow transplantation using HLA-identical sibling donors was performed in 29 patients with malignant blood diseases and in four patients with severe aplastic anaemia. Twenty-five patients received immunosuppressive therapy with cyclosporin A to minimize graft-versus-host disease (GVHD) and eight received methotrexate. Twenty-one of 29 patients (72%) with malignant blood diseases and three of the four patients with severe aplastic anaemia remained alive and disease-free from 0.5 to 16 (median, seven) months after transplantation. Acute GVHD, predominantly of the skin, occurred in 25 of 28 evaluable cyclosporin A recipients (of whom two died), and in all five evaluable methotrexate recipients. Mild chronic GVHD occurred in 10 of 16 evaluable patients. Interstitial pneumonitis occurred in five patients, of whom two died. HLA-identical sibling marrow transplantation is associated with a mortality similar to that of induction chemotherapy for acute leukaemia, and should be considered in adults with acute leukaemia in remission or relapse, chronic myelogenous leukaemia in metamorphosis or blastic transformation, lymphoma unresponsive to conventional therapy, and in severe aplastic anaemia.

Adolescent↗
PubMed1983

Identification of a structural gene for a RNA polymerase II polypeptide in Drosophila melanogaster and mammalian species.

Using subclones representing 14 kilobase pairs (kb) of DNA from the Drosophila melanogaster RNA polymerase II (EC 2.7.7.6) X-linked genetic locus, RpII, we have identified four poly(A)+ RNA transcripts in adult flies. The DNA encoding only one of these, a 7-kb transcript, cross-hybridized to mammalian DNA. DNA from alpha-amanitin-resistant (AmaR) Chinese hamster ovary (CHO) and human cells was used to transform the temperature-sensitive (TS) RNA polymerase II Syrian hamster mutant TsAF8. The acquisition of the TS+ AmaR RNA polymerase II phenotype was accompanied by the appearance of donor-DNA-specific restriction fragments that cross-hybridize to the D. melanogaster 7-kb transcript DNA. This D. melanogaster DNA and the related DNA detected in mammalian species must therefore be the structural gene for a RNA polymerase II polypeptide.

Animals↗
PubMed1976

Antibody-dependent cell-mediated cytotoxicity against melanoma cells induced by plasmapheresis.

Patients with disseminated melanoma were treated by repeated plasmapheresis using a continuous-flow blood-cell separator, as part of a study to investigate methods of removing factors from tissue fluids which block cell-mediated immunity. Using 51Cr release cytotoxic assays, it was found that plasmapheresis resulted in removal of serum blocking activity. Post-plasmapheresis sera taken from several patients also increased cell-mediated cytotoxicity by induction of antibody-dependent cell-mediated killing. This effect may have resulted from removal or alteration of circulating immune complexes in the serum. It is not known whether cytotoxic activity induced in this way improves the patient's immune response against their tumours. However, the procedure is well tolerated and these preliminary in-vitro results indicate that this form of therapy could act as an adjunct to other forms of treatment of advanced melanoma.

Antigen-Antibody Complex↗