[Analysis of lymphocyte subpopulations of the spleen in patients with gastric cancer and liver cirrhosis].
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Biomedical subjects
Publications and source records attributed to A Kameda.
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To elucidate the role of the spleen on immunosuppression of gastric and esophageal cancer, suppressor cell activities of spleen cells (SCs), splenic vein lymphocytes (SVLs) and peripheral blood lymphocytes (PBLs) were investigated. Concanavalin-A induced suppressor cell (Con-AS) activity of SCs was significantly higher in patients with gastric cancer than in those with benign diseases. Higher Con-AS activity of SCs was observed in esophageal cancer patients with tumors located in the lower portion of the esophagus. In comparison with suppressor activities of SCs and SVLs, the decrease of the predominance of suppressor precursors in SCs and the increase of the spontaneously activated suppressor cells in SVLs were noted with the advance of the tumors. Culture supernatants from splenic adherent cells significantly induced suppressor cell activities as well as did sera from splenic venous blood. From these results, it is concluded that the generation of suppressor precursors in the spleen is dependent on the location of tumors and that the maturation of suppressor cells occurs in the spleen by factors released from splenic adherent cells, then migrates into the peripheral blood.
Seven different recombinant viruses from the virulent Mahoney and the attenuated Sabin parental strains of type 1 poliovirus were constructed in vitro by using infectious cDNA clones. Monkey neurovirulence tests (lesion score, spread value, and incidence of paralysis) using these recombinant viruses revealed that the loci influencing attenuation were spread over several areas of the viral genome, including the 5' noncoding region. In vitro phenotypic marker tests corresponding to temperature sensitivity of growth (rct marker), plaque size, and dependency of growth on bicarbonate concentration (d marker) were performed to identify the genomic loci of these determinants and to investigate their correlation with attenuation. Determinants of temperature sensitivity mapped to many areas of the viral genome and expressed strong but not perfect correlation with attenuation. Recombinant viruses with Sabin-derived capsid proteins showed a small-plaque phenotype, and their growth was strongly dependent on bicarbonate concentration, suggesting that these determinants map to the genomic region encoding the viral capsid proteins. Plaque size and the d marker, however, were found to be poor indicators of attenuation. Moreover, virion surface characteristics such as immunogenicity and antigenicity had little or no correlation with neurovirulence. Nevertheless, viruses carrying Sabin-derived capsid proteins had an apparent tendency to exhibit less neurovirulence in tests on monkeys compared with recombinants carrying Mahoney-derived capsid proteins. Our results suggest that the extent of viral multiplication in the central nervous system of the test animals might be one of the most important factors determining neurovirulence. Moreover, we conclude that the expression of the attenuated phenotype of the Sabin 1 strain of poliovirus is the result of several different biological characteristics. Finally, none of the in vitro phenotypic markers alone can serve as a good indicator of neurovirulence or attenuation.
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The enhancement of antitumor effects by combination of biological response modifiers (BRM) was investigated on the basis of their action mechanisms. Experimentally, significant inhibition of tumor growth by combination treatment with BRM, which eliminated immune suppressive mechanisms and in turn enhanced immune responses, was observed. Furthermore, inhibition of tumor growth was observed under conditions of uniform biorhythm in mice and the effect of modification of biorhythm was enhanced by combination with BRM. Clinically, combination treatment of plasma exchange and LAK-cell adoptive immunotherapy was discussed.
The effects of intraperitoneal administration of OK-432 on tumor cells in ascites, in relation to the infiltration of effector cells and on the immune responses of the host, particularly, with regard to immune suppressive mechanisms, were investigated in 25 patients with cancerous ascites. The effects of OK-432 depended on frequency of the repeated and continuous administrations through a tube placed in the peritoneum during laparotomy. Infiltrations of neutrophils and lymphocytes were observed in the ascites within a short period after the administration and monocyte infiltration followed. Disappearance of tumor cells correlated well with the infiltration of these cells. No marked changes in the proliferative responses of peripheral blood lymphocytes were noted and decreases in serum inhibitory factor levels in sera were observed in patients given larger doses of OK-432. A marked reduction in Concanavalin-A-induced suppressor cell activities was observed after OK-432 administration. OK-432 administration probably leads to a disappearance of tumor cells by enhancing peritoneal effector cell activities and by inhibiting the induction of suppressor cell activities, in a dose dependent manner.
Infectious cDNA corresponding to the entire genome of the attenuated Sabin strain of type 1 poliovirus has been inserted into EcoRI site of bacterial plasmid pBR325. Two consecutive PstI fragments (nucleotide positions 1814 to 3421) of the infectious cDNA of the Sabin 1 strain were replaced by the corresponding DNA fragments prepared from an infectious DNA clone of the genome of the virulent Mahoney strain of poliovirus type 1. The exchanged segment encodes capsid protein VP1 and part of capsid protein VP3, a region in which a large number of amino acid differences between the attenuated Sabin and the parental, neurovirulent Mahoney strain cluster. The recombinant virus was obtained by DNA transfection of HeLa S3 cells, and several in vitro phenotypes of the virus were compared with those of the parental viruses. The recombinant virus was recognized by a neutralizing monoclonal antibody specific to the Mahoney strain. Growth of the Sabin strain of poliovirus has been shown to be quite dependent upon the bicarbonate concentration (d marker). The growth of the recombinant virus, however, was not highly dependent upon the concentration of bicarbonate in cell culture media, and thus resembled that of the Mahoney strain. On the other hand, the temperature-sensitive multiplication (rct marker) and the small-plaque morphology of the recombinant virus corresponded to the phenotype of the Sabin 1 strain. The in vitro recombination of infectious cDNA clones of genomic RNA and subsequent analysis of the growth properties of the recombinant virus have allowed us to correlate specific mutations in the genome of an RNA virus with certain biological characteristics of that virus.
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Plasma exchange was undertaken to remove the immunosuppressive factors in 25 advanced cancer patients who did not respond to immunochemotherapy. In the present studies, a postcentrifugal filter was tried, and the filtrated autologous plasma was replaced in 10 patients replaced by about 1000 ml in eight and by about 1600 ml in two. The improvement of subjective symptoms and reduction of tumors were observed in 15 (60%) and seven (28%) patients, respectively. It was suggested that immunosuppressive factors of a large molecular size could be selectively removed by the postcentrifugal filter.