Biomedical subjects
Publications and source records attributed to S Ramakrishnan.
A case is described of subcutaneous and mediastinal emphysema developing as a complication of lung function tests in an immunocompromised patient with presumed Pneumocystis carinii pneumonia.
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Transferrin plays a central role in cellular proliferation and proliferating cells have been shown to express transferrin receptors with increased density. We examined the effect of an immunotoxin consisting of anti-transferrin receptor monoclonal antibody (454A12) conjugated to recombinant ricin A chain (rRTA) on the proliferation of human corneal endothelium (HCE) in vitro. In proliferating cultures an immunotoxin (454A12-rRTA) concentration of 50 ng/mL reduced cell counts at day 7 by at least 89%, with no effect observed at 0.01 ng/ml. In contrast, cell counts were only minimally reduced in confluent cultures, even after 7 days' exposure to high concentrations of immunotoxin. These data suggest that 454A12-rRTA may be used to prevent growth of human corneal endothelium in pathological conditions such as the iridocorneal endothelial (ICE) syndrome.
A single subcutaneous injection of 0.5 mg cadmium chloride in Amphibian Ringer solution caused a significant decrease in secondary spermatogonial and primary spermatocytic stages in the semineferous tubules of frogs in 7 days. B3 cells of adenohypophysis and the activities of delta 5-3 beta-hydroxy steroid dehydrogenase and 17 beta-dehydrogenase in the Leydig cells were significantly increased in the same period. There were no significant changes in 3 days.
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Studies reported here indicate that an anti-Ia immunotoxin can eliminate the allostimulatory subpopulation of cells present within the islets of Langerhans without damaging the hormone-secreting cells. Such studies made use of an in vitro correlate of transplantation rejection, the mixed lymphocyte islet cell (MLIC) reaction. Using the MLIC, it was demonstrated that an anti-Ia immunotoxin removed cells capable of stimulating the MLIC in a dose-dependent fashion without altering the hormone-secreting functions of the remaining cells when challenged with glucose and theophylline. These studies suggest the feasibility of using such anti-Ia immunotoxins in islet allograft transplantation models to circumvent problems inherent in complement-mediated cytotoxicity, a previously documented effective form of inducing islet allotransplantation tolerance.
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Testicular synthesis of (14C)cholesterol and (14C)testosterone from (14C)acetate were investigated in mice treated with 5-thio-D-glucose at a dose of 33 mg/kg body weight/day for 21 days. The testicular synthesis of free cholesterol as well as steroids were significantly decreased. The steroid synthesizing enzymes, cholesterol esterase, cholesterol side-chain cleaving enzyme, total alpha-hydroxysteroid dehydrogenase and total beta-hydroxysteroid dehydrogenase, were also analysed. Cholesterol esterase and total beta-hydroxysteroid dehydrogenase were significantly reduced whereas total alpha-hydroxysteroid dehydrogenase was unaffected. Hence, a decrease in free cholesterol for steroid synthesis and a decreased activity of the steroidogenic enzyme, beta-hydroxysteroid dehydrogenase, were responsible for the diminished synthesis of testosterone.
ASTA Z 7557 potentiated the ex vivo efficiency of a T-cell directed immunotoxin containing pokeweed antiviral protein (PAP). We used an immunotoxin of pan-T monoclonal antibody 3-A1 directed against p41 antigen expressed both on normal and leukemic T-cells. Treatment with 3A1-PAP in combination with ASTA Z 7557 produced 7-8 logs elimination of target lymphoblastic leukemia cells. Our data suggest that this new strategy shows potential for more effective ex vivo marrow purging in autologous marrow transplantation for acute lymphoblastic leukemia.
Studies were performed to evaluate the anti-tumor activity of mafosfamid, a new synthetic derivative of cyclophosphamide. We tested its ability to eliminate lymphoblastic leukemia cells from autologous bone marrow grafts following a 30 min preincubation in a highly sensitive clonogenic assay. Treatment with 50-100 micrograms mafosfamid/ml eliminated more than 4 logs of contaminating clonogenic tumor cells from a 200-fold excess of normal bone marrow. Flow cytometric studies showed differences in cell cycle kinetics between mafosfamid-resistant and mafosfamid-susceptible tumor cell clones. Compared to drug susceptible clonogenic tumor cells, clones that resisted treatment with 100 micrograms mafosfamid/ml exhibited a smaller percentage of cells in S-phase, indicating that mafosfamid is mostly cytotoxic to rapidly cycling tumor cells. The combination of mafosfamid and a target cell selective immunotoxin containing pokeweed anti-viral protein was superior to mafosfamid alone or immunotoxin alone for purging mafosfamid-resistant leukemic cells from human marrow.
The effect of short surgical procedures on paracetamol elimination was studied in seven male patients undergoing surgery with epidural anaesthesia. Five healthy volunteers who did not undergo surgery served as a control group. Paracetamol concentration was measured in saliva at various intervals 1 day before and after surgery. Paracetamol half-life (t1/2,z) decreased and metabolic clearance rate (CL) increased after surgery as compared to preoperative values. The results suggest that surgical stress may enhance the hepatic metabolism of paracetamol.
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An immunotoxin was synthesized with pokeweed antiviral protein and an IgG1 monoclonal antibody directed against human B and pre-B cells. The B43 murine monoclonal antibody does not react with normal human bone marrow precursor cells. The immunotoxin bound to all Burkitt's lymphoma cell lines that were tested but not to human peripheral blood T cells. The ability of antibody-toxin conjugate to inhibit human lymphoblast cell lines was checked in a clonogenic assay system. The immunotoxin in the presence of chloroquine elicited 5.8 logs of killing of Burkitt's lymphoma cells (B-ALL). The efficient inhibition of clonogenic growth of B-ALL cells was not affected by the presence of normal bone marrow cells. The immunotoxin was not very toxic to pluripotent stem cells; less than 50% of the stem cells were lost under conditions where 5.6 logs of clonogenic lymphoma cells were eliminated from a 100-fold excess of normal marrow cells. Further, when assayed by long-term human bone marrow cultures, immunotoxin treatment did not result in a significant loss of pluripotent precursor cells.