Biomedical subjects
Publications and source records attributed to S Tsuru.
The adsorption and chromatographic properties of hydroxyapatite sorbents for application to different viruses have been investigated. The strong adsorption of viruses was observed on macroporous hydroxyapatite with hydrophilic properties of the sorbent surface. The viruses were purified on this sorbent without loss of biological activity. The column can be used for virus vaccine production.
The undifferentiated carcinoma cell line (HMG) was established from a nude mouse tumor which had been produced by transplantation of a intraperitoneal tumor of 27-year-old woman. The HMG cell line has the following biological properties. 1. The HMG cells are round to oval in shape and grow as floating cell aggregates like a rouleau or a cluster of grapes. 2. 100 passages have been carried out over a year, and the population doubling time is about 17 hrs. 3. In the original tumor, keratin and vimentin were expressed simultaneously, in HMG cells, however, only localization of vimentin was confirmed. 4. By chromosomal analysis, over 90% of the cells revealed 46, XX, with no karyological abnormalities, at passage 82. 5. When heterotransplanted into the subcutis of a nude mouse, HMG cells produced a undifferentiated carcinoma resembling the original tumor.
General practitioners (GPs) play an important part in community health care. Their opinion regarding introduction of a medical information network system using a personal computer and factors influencing the decision to introduce such a system were surveyed among 977 randomly sampled GPs. A response from 727 GPs was obtained. Based on a two stage selection method, 20 factors were selected as effective factors among the 73 factors surveyed, with the following results: (1) Responses to the question concerning the approval of system introduction were classified into three groups: "not necessary + too early to make a decision (DA)" (DA group), "approve (A)" (A group) and "undecided (UD)" (UD group). Each group had nearly equal numbers of respondees. (2) Significant effective factors were "experience with personal computers", "a desire to use a personal computer", "a desire to use a computer-diagnosis-system", "cost", and "a volition to operate a computer by himself". (3) The "A group" had high experience and affirmative opinions, while the "DA group" had low experience and negative opinions. The "UD group" also tended to respond with "do not know" regarding the factors. (4) Approval of system introduction requires providing basic knowledge on computers, opportunities for positive experience with computers, and practical examples of problem solutions in a general practitioner's work.
The cell content of the peritoneal exudate was examined 4 days after an intraperitoneal injection of glycogen in uninfected and Paragonimus westermani-infected guinea pigs. In uninfected animals a reduction in macrophage count and an accumulation of granulocytes in the exudate were observed at 3 and 6 hr after an intraperitoneal injection of purified neutral thiol protease from P. westermani metacercariae. No such effect occurred after the enzyme was injected into infected animals. At 9 hr after enzyme injection, vacuoles were found in the cytoplasm of macrophages in uninfected animals.
Relationship between tumor cell growth and cell cycle and influence of antitumor drugs on the cell cycle regulation were investigated by the use of murine EL-4 tumor. Cell growth curve of EL-4 cells was well related to the cell cycle pattern analyzed by two color flow cytometry both in vivo and in vitro. The ratio of S phase rapidly increased in early log phase and decreased from late log to plateau phases. The ratio of G0/G1 phase showed a reciprocal change. Minimum effective doses of 5-fluorouracil (5-FU) and CDDP on EL-4 growth in vitro were 1 x 10(-6) M and 0.5 micrograms/ml, respectively. At such doses, 5-FU showed an accumulation in early S phase and CDDP showed a partial synchronization in S phase and subsequent accumulation in late S and G2 + M phase. In case of in vivo administration with 5-FU (20 mg/kg/day) ratio of S phase was higher than in untreated control mice at day 2-3 but decreased rapidly thereafter. Mice administered with CDDP (5 mg/kg/day) showed a decrease in S phase from day 2 and completely rejected the tumors by day 5. From these results, each phase of cell cycle was influenced by the cell growth characteristics and the cell cycle pattern was dynamically changed according to the mode of action of antitumor drugs. Moreover, in vivo effects of these drugs can be evaluated adequately by the analysis of the cell cycle.
The relationship between depression of early protection against influenza virus infection and the decrease in the number of peripheral polymorphonuclear leukocytes in cyclophosphamide-treated mice was investigated by means of a novel synthetic compound, Y-19995 [2,4'-bis(1-methyl-2-dimethyl-aminoethoxyl)-3-benzoylpyridine dimaleate], which had been shown to exert a potent restorative effect on leukocytopenia in immunocompromised hosts. Following intranasal inoculation with influenza virus (1.5 x 10(3) plaque-forming units) into untreated mice, the pulmonary virus titer progressively increased during 3 days and decreased gradually from day 7 after infection. The treatment with cyclophosphamide 2 days before infection markedly enhanced the pulmonary virus multiplication from the early phase of infection, and the higher virus titer was maintained thereafter. When mice were given Y-19995 after cyclophosphamide treatment, virus titers from the early to late phases of infection were lower than those in untreated mice. The number of peripheral polymorphonuclear leukocytes in cyclophosphamide-treated mice rapidly decreased and returned to normal levels only 9 days after the treatment, while such leukocytopenia was prevented to some extent and the leukocyte count was restored completely up to 7 days by postcyclophosphamide treatment with Y-19995. Furthermore, the treatment with Y-19995 augmented the inactivation of virus by the polymorphonuclear leukocytes. However, the virus inactivation by alveolar macrophages was modified only slightly by Y-19995 treatment. In addition, Y-19995 treatment could potentiate antibody-dependent cell-mediated cytotoxicity of polymorphonuclear leukocytes against the virus-infected target cells, and the production of serum neutralizing antibody to influenza virus in untreated and cyclophosphamide-treated mice. Y-19995 revealed neither antiviral nor interferon-inducing activities.(ABSTRACT TRUNCATED AT 250 WORDS)
We have developed a simple method for assessing the oxidative metabolic burst of peripheral blood leukocytes with a minute amount of whole peripheral blood by flow cytometry according to the method of Bass et al. with some modification. By this method, we can measure the H2O2 production by both granulocytes and monocytes in the same blood sample. The oxidative product formation by peripheral blood neutrophils can be monitored sequentially in the same mouse infected with E. coli. The mice infected intravenously with 0.1 LD50 of the bacteria showed increased basal activities from an early stage of infection; those infected intraperitoneally with the same dose of the bacteria showed a delayed enhancement. In case of infection with 0.01 LD50, the enhanced basal activities lasted for only a short period of time. The H2O2 production was correlated well with the clearance of the infected bacteria. These results demonstrated that the oxidative-product formation by peripheral blood neutrophils is affected by both the route and the dose of infection.
In the present report, we compared activities of polymorphonuclear leukocytes (PMN) such as phagocytosis and bactericidal activity in vivo with those in vitro in sarcoma 180 (S 180)-bearing mice. Mice showed a remarkable leukocytosis and in increase in PMN fraction of peripheral blood leukocytes (PBL) after intraperitoneal injection of S 180 cells. Tumor-bearing mice infected with Escherichia coli (E. coli) intravenously and intraperitoneally showed an apparent delay in the clearance of bacteria compared to the non-tumor-bearing control mice. However, PBL of tumor-bearing mice showed a high phagocytic activity against beads and a high chemiluminescence (CL) activity. Dichlorofluorescein (DCFH) oxidation capacity of peripheral blood PMN in S 180-bearing mice after stimulation with phorbol myristate acetate (PMA) was about the same or a little stronger than that in control mice. On the contrary, serum and ascites of tumor-bearing mice strongly suppressed the phagocytic and bactericidal activities of casein-induced PMN against E. coli. During the early phase of E. coli infection, serum level of complement (C3) was not depressed in tumor-bearing hosts. From these results, it is concluded that leukocytosis and activation of functions of PMN in tumor-bearing mice were observed in vitro but they were not effective for the protection in the early phase of actual E. coli infection in vivo. The delay of in vivo clearance may be accounted for by a suppressive effect of serum components in tumor-bearing mice.
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This study was undertaken to examine the effects of immunization with Sporothrix schenckii and oral potassium iodide (KJ) administration on the chemiluminescence (CL) response of mouse polymorphonuclear leukocytes (PMNs) in experimental murine sporotrichosis. When N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) particles were used as foreign bodies to be phagocytosed, the time to the peak CL response of the PMNs in an immunized group was shortened in comparison with a non-immunized control group, and the CL intensity was found to be prolonged. Whereas administration of KJ resulted in a reduction of the CL intensity in non-immunized mice, in immunized mice it caused a rise in CL intensity. When the foreign bodies used as targets for phagocytosis were Sp. schenckii, changes similar to the above occurred, but CL production was reduced.
The purpose of this study was to elucidate the availability of hydroxyapatite (HAp) granules as a chemoembolic agent in chemo embolization therapy. A mixture of adriamycin (ADM) and an embolic agent (HAp, Lipiodol) was injected via hepatic artery in normal Wistar rats. Then the concentration of ADM in the liver serum transaminase level were measured serially. The remaining ADM in the liver was higher in groups with HAp granules than the others. The serum transaminase, however, were lower in the HAp groups. There are some advantages of HAp using as a chemo embolic agent. (1) HAp is a physiological biomaterial and seem to be safe for human. (2) HAp granules injected into the liver are easily detectable by X ray and ultrasonography. (3) HAp granules have a large surface area and this characteristic is suitable for a carrier of drugs. It is concluded that HAp granules have some necessary prerequisites for a chemo embolic agent and the application to clinical practice may be expected.
Antigenicity of tricalcium phosphate (TCP) ceramics which were supplied by two Japanese manufacturers and a manufacturer of United States was studied by means of delayed skin reactions in guinea pigs. Skin reactions were elicited 13 days after being immunized by intradermal injection of the ceramics into the dorsal flanks of guinea pigs. After 24 and 48 hr, these reactions were assessed by measuring the diameter of the erythema, the degree of hemorrhaging and its induration. Antigenicity was not detected in the TCP obtained from the Asahi Optical Co., Ltd. and the Kyocera Corporation by means of skin reactions. In contrast, TCP from Miter, Inc. (Synthograft) raised a delayed type hypersensitivity (DTH) 24 hr after antigen elicitation. The reaction appeared to be based on tuberculin type and Jones-Mote type of reactions. Arthus reactions were not observed in either the normal groups or groups immunized with TCP.
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Immunomodulatory effects of cholera toxin (CT) were investigated in a murine model using various immunological parameters. C3H/HeN mice were injected with 2 micrograms of CT at various intervals (from 6 h to 21 days) before the immunological assays. Thymocytes were markedly decreased in their absolute number, and the phenotypes in such cells were clearly shifted from Thy1.2high+ PNAhigh+ to Thy1.2low+ PNAlow+ 2-4 days after the CT treatment. Spleen T cells were relatively increased, while surface IgM positive B cells were rather decreased. Natural killer activity and in vivo and in vitro cytotoxic T lymphocyte activity were markedly suppressed during the early stages after the CT treatment but recovered completely within 21 days. Mixed lymphocyte reaction was profoundly suppressed at least for the 1st week after the CT treatment. Furthermore, EL-4 tumor of C57BL/6 origin grew progressively and killed the recipient C3H mice when such tumor cells were inoculated 6 h after the CT treatment. On the contrary, a marked augmentation of direct (IgM) and indirect (IgG) plaque-forming cell responses to sheep red blood cells was seen after CT treatment. Delayed footpad reaction to SRBC was also augmented after CT treatment. As the mechanisms, both direct augmentation of CD4+ T cells and direct suppression of CD8+ T cells appeared to occur at a time due to the CT treatment. An indirect effect of CT through the release of the endogenous steroids was dismissed in the present study. Taken together, CT appears to have differential immunomodulatory effects on various immune effector cells through various mechanisms.
Passage of peripheral blood lymphocytes through a column of hydroxyapatite resulted in a 7-20-fold depletion of immunoglobulin-bearing cells, a 20-fold depletion of monocytes, and a 1.3-fold enrichment of T cells. The effluent population was virtually devoid of B lymphocyte precursors and monocytes, whereas helper cell and suppressor cell populations remained intact. This method will facilitate the rapid preparation of T-enriched cell populations.
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