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Biomedical subjects

H Ovadia

Publications and source records attributed to H Ovadia.

11 recordsLinked to original sources

Chronic-relapsing experimental autoimmune encephalomyelitis (CR-EAE): treatment and induction of tolerance, with high dose cyclophosphamide followed by syngeneic bone marrow transplantation.

We examined the effect of acute immunosuppression with high dose cyclophosphamide (CY), followed by syngeneic T-cell-depleted bone marrow transplantation (SBMT) on chronic-relapsing autoimmune encephalomyelitis (CR-EAE) induced in SJL/J mice by immunization with mouse spinal cord homogenate (MSCH) in adjuvant. Treatment of mice on day 9 post immunization, before the appearance of clinical signs of the disease, delayed the onset of paralysis, but did not affect its clinical course. Treatment on day 2-3 after the first clinical signs led to complete regression of the disease. During a period of 3 months, only one of the 15 mice treated after the the onset of CR-EAE relapsed, as compared to a total of 21 relapses in the 15 untreated animals. A rechallenge with MSCH in adjuvant on day 78 after immunization induced a severe relapse in all untreated mice, with 78% mortality; in contrast, only 25% of mice treated with CY and SBMT relapsed when similarly rechallenged. Lymphocytes from mice treated with CY and SBMT showed reduced in vitro proliferative responses to myelin basic protein (GMBP) and PPD, even after the rechallenge with MSCH. Our results show that high dose CY for elimination of immunocompetent lymphocytes, followed by SBMT rescue, suppresses CR-EAE and induces tolerance to the immunizing antigens. These results may encourage attempts to apply a similar therapeutic principle in life-threatening human neurological autoimmune diseases.

Animals

[Mathematical modelling of open-wedge tibial osteotomy and correction tables].

This study analyzes mathematically the orientation of the superior tibial epiphysis in frontal and sagittal planes for knees with genu varum arthrosis. The assessment of the opening is determined mathematically for the osteotomies; this leads to the establishment of tables which can be used in practise during upper tibial osteotomies.

Humans

Normal immunosuppressive protein inhibition of human and murine lymphoblastoid cell line proliferation.

Normal immunosuppressive protein, prepared from human plasma by DEAE-cellulose chromatography, inhibits DNA synthesis in human cell lines of lymphocytes of both T and B origin. It also inhibits [3H]thymidine incorporation in mouse cell lines. Normal immunosuppressive protein was able to inhibit the proliferation of these cells, although they were already transformed and had a high rate of DNA synthesis. On the other hand, it does not inhibit myeloid cells or fibroblasts.

Alpha-Globulins

Normal immunosuppressive protein purification and quantitative estimation experiments.

An improved method for the preparation and purification of normal immunosuppressive protein (NIP) is described. The purified material has a molecular weight between 10,000 and 25,000. Its biological and serological activity is approximately 10--20 times higher than that of the crude fraction. An antibody to normal immunosuppressive protein prepared in rabbits made the quantitative estimation of NIP by a haemaggluination inhibition test possible. Similarly, a very sensitive assay for the quantitative determination of NIP by its inhibitory effect on the proliferation of EL-4 tumor cells is also described. Eluates prepared from polyacrylamide gels were active in inhibiting EL-4 tumor cell proliferation and neutralized the anti-NIP activity in the haemagglutination inhibition test.

Animals

Normal immunosuppressive protein: in vitro inhibition of DNA synthesis in T and B lymphocytes and lymphoid cell lines.

The biologic activity of normal immunosuppressive protein (NIP) isolated from human plasma was studied. NIP was found to inhibit the proliferation of both T and B lympohcytes in vitro. It suppressed the DNA synthesis of normal mouse lymphocytes responding to the mitogens phytohemagglutinin and lipopolysaccharide, as well as the [3H]Thymidine and [3H]leucine uptake by T and B lymphoid cell lines of human and murine origin. The lymphoid specificity of NIP was demonstrated by showing that DNA and protein synthesis of normal and transformed fibroblasts and other nonlympohid cell lines was not affected by NIP treatment. Furthermore, by using lymphoid cell lines we were able to show that 1) NIP inhibits the process of ongoing DNA and protein synthesis; 2) the duration of the cells' exposure to NIP is crucial for obtaining optimal effect; and 3) the inhibitory effect of NIP is totally reversible.

Animals

Normal immunosuppressive protein: inhibitory effect on immune response against tumour cells.

Normal immunosuppressive protein isolated from human plasma was found to inhibit the generation of primary cytotoxic effector lymphocytes against allogeneic tumour cells in vitro. Total inhibition was observed when NIP was present during the early stages of the sensitization process. In contrast, the generation of secondary cytotoxic lymphocytes in vitro was only slightly inhibited even though large amounts of NIP were used. The inhibition of target cell lysis by sensitized lymphocytes required long preincubation of a relatively small number of effector cells with large amounts of NIP and was most significant when tested at low effector: target cell ratios. Under the same conditions NIP showed no inhibitory effect on the cytotoxic activity of immune macrophages. The present in vitro experiments suggest that NIP exerts its effect through inhibition of DNA synthesis and cellular proliferation and to a limited extent only, by inducing specific suppressor cells.

Alpha-Globulins