Stimulation of thrombopoiesis in mice bearing experimental tumors

Significant increase (p less than 0.05) in circulating platelet counts was observed in a wide spectrum of experimental tumors in mice. The mechanism of this abnormality was investigated in strain A mice bearing a transplantable ascites tumor, Sarcoma 180 (S 180). Thrombocytosis observed in the tumor hosts was not due to prolonged platelet surviva], as 51Cr platelet half-life was normal. On the other hand, stimulation of thrombopoiesis, expressed in terms of platelet 75Selenomethionine (75SeM) incorporation, appeared to be the primary reason for elevated platelet counts in the tumor-bearers. Evaluation of thrombopoietic activity in the femoral marrow and spleen by measuring organ uptake of 75SeM and megakaryocyte counts indicated that tumor-induced stimulation in thrombopoiesis may be attributed to enhancement in splenic activity. Pretreatment of normal mice with tumor ascites or tumor cell-conditioned medium resulted in enhancement in thrombopoiesis. The findings suggest the production of some factor(s) by the tumor cells which probably mediate the stimulation of platelet production in tumor hosts.     

The first mechanism-based inactivators for angiotensin-converting enzyme.

The first example of mechanism-based inactivation of angiotensin-converting enzyme (ACE) is described for N-[N-(cyanoacetyl)-L-phenylalanyl]-L-phenylalanine (compound 1). It is proposed that an ACE-mediated deprotonation of 1 unmasks a ketenimine intermediate, which traps an active-site nucleophile, and hence irreversibly modifies the enzyme. In competition with the inactivation reaction, ACE also hydrolyzes 1 with a partition ratio of 8300 (i.e., kcat/kinact). Since the corresponding keto analogue, N-[(R)-2-benzyl-5-cyano-4-oxopentanyl]-L-phenylalanine (compound 4), does not inactivate the enzyme, it is suggested that the NH in compound 1 is critical for the proper active-site anchoring of the inhibitor for the inactivation process to take place.     

Evaluation of ceruloplasmin concentration in prognosis of human cancer

The serum ceruloplasmin concentration was determined in cancer patients before and after radiotherapy, and after relapse of cancer, The ceruloplasmin concentration in patients who responded to therapy, decreased to the range of normal controls. In patients who did not respond to treatment, the ceruloplasmin concentration was more or less elevated. In patients with relapse of cancer, the ceruloplasmin concentration was higher than before treatment.     

Studies on capsaicin inhibition of chemically induced lipid peroxidation in the lung and liver tissues of rat

Previous work from this laboratory has already indicated that capsaicin, stabilizes the rat lung membrane lipid system on long-term treatment. This stabilization of the membrane is further supported by our present findings that capsaicin pretreatment causes significant inhibition of various chemically induced lipid peroxidative changes at both cellular and subcellular levels. Both in vivo and in vitro studies, using whole lung and liver tissue slices and mitochondrial and microsomal fractions, have shown that capsaicin pretreatment inhibits peroxidative changes at both cellular and subcellular levels. Both in vivo and in vitro studies, using whole lung and liver tissue slices and mitochondrial and microsomal fractions, have shown that capsaicin pretreatment inhibits peroxidative changes induced by different chemical irritants such as chloroform, dichloromethane, carbon tetrachloride as well as ferrous sulphate.     

Biotype traits and antibiotic susceptibility of Vibrio cholerae serogroup O1 before, during and after the emergence of the O139 serogroup.

Sixty-nine strains of Vibrio cholerae O1 isolated at different times were analysed to investigate if there were any differences among the O1 strains isolated before, during and after the advent of the O139 serogroup. Of the 69 O1 strains examined, 68 belonged to the Ogawa serotype while one belonged to the Inaba serotype. With the exception of one strain all other strains of V. cholerae O1 belonged to the eltor biotype. A single O1 strain isolated before the emergence of the O139 serogroup could not be classified as either eltor or classical biotype because it was resistant to both classical and eltor specific bacteriophages. Marked variations in the susceptibility to antibiotics of V. cholerae O1 isolated during the different periods were observed. In addition, strains of V. cholerae isolated after the epidemic of serogroup O139 in Calcutta showed an expanding R-type with resistance to a variety of drugs as compared to the O1 strains isolated before the advent of the O139 serogroup. From this study, it is clear that there is a substantial mobility in genetic elements of V. cholerae O1 which necessitates a continuous monitoring to keep abreast of the changing traits of the etiologic agent of cholera.     

Immunomodulation during prolonged treatment with combined interleukin-2 and interferon-alpha in patients with advanced malignancy.

Treatment with combined IL-2 and alpha-IFN has resulted in synergistic antitumour efficacy in animal studies. The mechanisms responsible for this synergy remain unclear. In this study, several immune parameters which might be involved in mediating antitumour activity have been monitored serially in 15 patients with advanced malignant melanoma or renal cell cancer during treatment with concurrent IL-2 and alpha-IFN. Both drugs were given subcutaneously in low to moderate (outpatient) dosages but for a prolonged duration. This treatment resulted in remarkable immunomodulation. In vivo induction of cytotoxicity against K562 and Daudi target cells was consistently seen, and percentages of peripheral blood cells expressing CD 25 (IL-2 receptor) and CD 56 (Leu-19) increased. In vitro proliferation of lymphocytes in response to IL-2 was enhanced during the treatment periods, whereas spontaneous proliferation was inhibited. Moreover, correlations between immune parameters and subsequent clinical responses were present in the early phase of the study. Cytotoxicity levels generated in vivo as well as the percentage of CD 56+ lymphocytes were higher in patients who responded to treatment than in non-responders. In contrast, responders had lower levels of CD 25+ cells. These findings indicate that it might be possible to select patients who are likely to benefit from prolonged immunotherapy.     

Epidemiological study of the victims of vehicular accidents in Delhi.

The mortality and morbidity connected with road traffic accidents are increasing at an alarming rate throughout the world as a direct result of the rapid industrialization and increase of fast moving vehicles combined with lack of traffic sense of road users of this country. Epidemiological aspects manifested in vehicular accidents in New Delhi during the year 1983-84 are illustrated here.