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Biomedical subjects

J R Hobbs

Publications and source records attributed to J R Hobbs.

At least 19 recordsLinked to original sources

Bone marrow transplants in genetic diseases.

The first paper [9] advocating the displacement use of bone marrow transplantation (DBMT) to treat a variety of genetic metabolic diseases (including thalassaemia major) was put before a European Working Party in 1978. It evolved from mainly Westminster experience which showed the need [6] for DBMT and first successfully used donors other than matched siblings [9]. The principles of using DBMT to install a donor marrow as a component factory which can last a lifetime are outlined. It is not a panacea, being applicable to only about 7% of known inborn errors. Worthwhile correction of some 50 previously disabling diseases in over 700 patients has already been achieved worldwide and for most of the survivors no further treatment is used after 1 year. Guidelines for future extension, including gene transplants, are offered. The superior results of elective DBMT (about 95%) should encourage paediatricians to aim for earlier diagnoses and evaluations for transplants.

Bone Marrow Transplantation

Timing of cyclosporin-A therapy for abrogation of HVG and GVH responses in rats.

Treatment with cyclosporin A was most effective in abrogating popliteal-lymph-node enlargement induced by host-versus-graft and graft-versus-host reactivity in rats when started before injection of donor-strain lymphocytes. Popliteal lymph-node enlargement was never completely abolished, and splenic lymphocytes from recipients treated with cyclosporin A showed no significant reduction in their response to donor-strain lymphocytes in mixed lymphocyte cultures, suggesting that clonal deletion had not taken place. Mixed lymphocyte cultures also indicated that cyclosporin treatment had not reduced the antigenicity of recipient lymphocytes towards donor strain.

Animals

Thymosin-inducible 'null' cells in atopic eczema.

Thirty children with atopic eczema were compared with an equal number of age-matched healthy children. The mean peripheral blood T-lymphocyte level was lower in the eczema group (mean 1,197/mm2 as against 1,702/mm3; P = 0 . 003). This difference was abolished in vitro by thymosin, a thymic hormone extract. Positive correlations were found between eczema severity and: eosinophilia; hyperimmunoglobulinaemia E; but not T lymphopaenia. Thymosin-inducible T-cell (Ti) counts correlated with plasma IgE levels, suggesting that these Ti cells may be immature suppressor T cells. If this T-cell deficiency represents inadequate suppression of IgE responses, then a trial of treatment with thymosin appears to be warranted.

Adolescent

Crossreaction of antilymphocyte globulin with human granulocyte colony-forming cells.

Clinical preparations of horse antilymphocyteglobulin (ALG) were found to inhibit human bone marrow granulocyte colony growth. This effect was enhanced by complement and was dose dependent, being almost complete at ALG concentrations of 100 microgram/ml. Inhibition was a property of ALG but not of normal horse globulin. However, short incubation of ALG with bone marrow cells occasionally stimulated colony growth and normal horse globulin regularly stimulated it. Three hours' incubation of bone marrow cells with ALG was needed to produce consistent colony inhibition, which was measurable as a reduction in the expected number of colonies and as a fall in the colony: cluster ratio of surviving cell aggregates. Absorption of ALG on acute myeloid leukaemia blast cells removed the inhibiting property of the ALG while preserving its lymphocytotoxic action. Serum from two patients receiving ALG treatment inhibited colony growth for up to 48 hours after ALG administration. The results suggest the presence in ALG of antibodies specifically cytotoxic to myeloid stem cells which may relate to its myleosuppressive properties in vivo, and also indicate that it should be possible to remove antimyeloid antibodies from ALG by absorption. The use of such purified ALG would have advantages in clinical bone marrow transplantation.

Antilymphocyte Serum

An evaluation of the Hyland laser nephelometer PDQ system for the measurement of immunoglobulins.

The Hyland laser nephelometer PDQ system for the assay of specific proteins is described. The results of evaluating the system to measure immunoglobulins IgA, IgG, and IgM are summarised. Within-batch and between-batch precision, accuracy, reliability, and safety are discussed. This instrument represents an important development in the immunochemical assay of proteins in clinical medicine. The speed, precision, and convenience of this new generation of discrete nephelometric analysers make such systems attractive to the clinical chemist.

Autoanalysis

T-cell depletion and in vitro thymosin inducibility in asthmatic children.

Thirty asthmatic children were compared with an equal number of age-matched healthy children. The mean peripheral blood T-lymphocyte level without foetal calf serum was lower in the asthmatic group (mean 970/mm3, as against 1740/mm3; P less than 0.0001), but this difference was abolished by adding foetal calf serum or thymosin, thus explaining how quite severe T-cell deficiency can be missed by widely used methods. The degree of eosinophilia and the degree of elevation of the plasma IgE level in the asthmatic patients were positively correlated. Positive correlations were also shown between the degree of severity of the asthma, the degree of eosinophilia and the degree of elevation of the plasma IgE level, but not the degree of depression of the T-cell numbers. If this T-cell deficiency reflects an inadequate suppression of IgE responses, a clinical trial of thymosin appears to be warranted.

Adolescent

Thymosin-inducible lymphocytes in the peripheral blood of patients with malignant melanoma.

E rosette-forming (T) lymphocytes and surface immunoglobulin-bearing lymphocytes were estimated in 85 patients with malignant melanoma. The melanoma patient group had lower mean levels of T lymphocytes and higher mean levels of immunoglobulin-bearing (? B) lymphocytes than did normal subjects. The absolute and percentage depressions of T-cell levels in the melanoma patients were stage-related, as was the depression of total lymphocyte and B-lymphocyte levels. The T lymphopenia in the melanoma patients could, in vitro, be partially abolished by fetal calf serum (as used in many E rosetting methods), and could be totally abolished by thymosin fraction 5 (Hoffmann-La Roche) at optimum concentration. In view of the ability of thymosin to restore T cells to normal levels in all of the T-lymphopenic patients, a clinical trial of this hormone in selected melanoma patients of all stages appears to be warranted.

Adolescent