Determinant selection is a macrophage dependent immune response gene function

Immune response (Ir) genes are linked to the species histocompatibility complex and define as yet uncharacterised phenotypic products which control the immune response to thymus dependent antigens. Antibody formation and antigen induced T lymphocyte proliferation are two examples of immune phenomena which, in vivo and in vitro, operate under Ir gene influence. To clarify their mechanism of action and cellular location, we have examined the contribution of antigen structure (amino acid sequence and conformation to Ir gene control of antigen recognition by T lymphocytes) as well as to the critical role played by the antigen presenting macrophage in expression of that control. We report that immune response gene control of antigen recognition operates at least in part at the level of the macrophage.     

Two monoclonal antibodies against different antigens using the same VH germ-line gene

Immunoglobulin diversity seems to arise largely by three mechanisms: (1) the existence of several germ-line genes, which must be rearranged before expression--that is, V and J for the light (L) chains, V, D and J for the heavy (H) chains; (2) somatic events, including mutations and gene conversion; and (3) combinatorial association of heavy and light chains, leading to the proposal that random pairing of p X H and q X L chains might generate p X q antibody molecules expressing discrete specificities. As heavy and light chains derived from the same immunoglobulin molecule would frequently reassociate preferentially, it is likely that only a fraction of potential heavy--light pairs actually provides "valid' antibodies. As a consequence of combinatorial heavy--light chain pairing, antibodies of discrete specificities sharing the same VH region, associated with distinct light chains (or vice versa) should be encountered. We report here that two heavy chains, derived from the same VH germ-line gene, may be present in anti-NP or anti--GAT antibodies, depending on their association with a specific lambda or kappa light chain, respectively.     

Dissociation of glucocorticoid effects of C-21 steroids at high concentrations in thymocytes

Summary A dissociation between inhibition of RNA synthesis and cell lysis was observed when thymocytes of adrenalectomized rats were incubated with high concentrations of pregn-4-ene-11-ol-3, 20-dione and pregna-1,4-diene-11-ol-3,20-dione. In contrast, no dissociation of these effects was found with the typical glucocorticoids cortisol and corticosterone, nor with their 1,4-diene analogs under the same conditions.Acknowledgments. This work was supported by grants from the Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina to the Instituto de Biologia y Medicina Experimental and the Programa de Regulación Hormonal y Metabólica as well as by financial help from the Secretaría de Ciencia y Tecnología.     

Serum inhibitory activity on granulocyte-macrophage colony formation

Summary Normal and chloroform-extracted human sera, fractionated by Sephadex column chromatography, have been tested for inhibitory activity on granulocyte-macrophage (GM) colony formation. It was found that this activity is connected with lipoproteins (inhibitors of granulocyte-macrophage colony stimulating factor) and low molecular weight substances (7000; 13,000) which can act as specific polypeptide chalones.     

Proteolytic activity on endogeneous substrates in cell-free extracts ofTrypanosoma cruzi

Summary Cell-free extracts ofTrypanosoma cruzi contain proteolytic activity able to degrade endogenous substrates. The activity was maximal at pH 3 to 4, had an optimal temperature of 65°C, and was strongly inhibited by N--p-tosyl-L-lysine chloromethyl ketone.This investigation received financial support from the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, the Fundación Julio Cherny, and the Ministerio de Salud Pública y Medio Ambiente de la República Argentina. The authors gratefully acknowledge the technical assistance of Mr Esteban Bontempi.     

Survival and endogenous spleen colonies of irradiated mice after skin wounding and hydroxyurea treatment

Summary Wound trauma-induced survival from radiation may be related to increased mitosis in hematopoietic cells. This is supported by the cell cycle-dependent drug hydroxyurea, which 1. blocked survival of wounded mice injected 2 or 3 days after 900 rad and 2. reduced the number of endogenous CFU-s in wounded mice injected shortly before 700 rad.Supported by the Armed Forces Radiobiology Research Institute, Defense Nuclear Agency, under Research Work Unit MJ00018. Views presented in this paper are those of the authors; no endorsement by the Defense Nuclear Agency has been given or should be inferred.Research was conducted according to the principles enunciated in the Guide for the Care and Use of Laboratory Animals prepared by the Institute of Laboratory Research, National Research Council.     

The free radical oxidation of the tetrahydrocannabinols

Summary The free radical oxidation of ¹ and ⁶-tetrahydrocannabinol has been examined by spin trapping techniques and intermediates that would lead to cannabinol have been trapped. The 1st step in the oxidation of ¹-THC involves the removal of 3-H, while for ⁶-THC, either 2-H or 5-H. Intermediates were isolated which could be pyrolysed to the diene and cannabinol.