[Electric dichroism].
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Biomedical subjects
Publications and source records attributed to M Shirai.
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Methimazole (MMI) (>0.1 mmol kg(-1), p.o.) given in combination with DL-buthionine sulphoximine (BSO) (3 mmol kg(-1), i.p., 1 h before MMI administration), an inhibitor of glutathione (GSH) synthesis, caused liver injury in mice. The injury was characterized by centrilobular necrosis of hepatocytes and an increase in serum alanine transaminase (ALT) activity. Methionazole (2 mmol kg(-1)) alone resulted in only a marginal increase in serum ALT activity, but produced no histopathological changes in the liver. Pretreatment with hepatic cytochrome P-450 monooxygenase inhibitors--cobalt chloride, isosafrole, methoxsalen, metyrapone and piperonyl butoxide-prevented or tended to suppress the hepatotoxicity induced by MMI in combination with BSO. Treatment with N,N-dimethylaniline and ethyl methyl sulphide, competitive substrates of flavin-containing monooxygenases (FMO), also resulted in remarkable suppression of the hepatotoxicity caused by MMI in combination with BSO. These results suggest that MMI is activated by reactions mediated by both cytochrome P-450 monooxygenases and FMO, and that the inadequate rates of detoxification of the resulting metabolite are responsible for the hepatotoxicity in GSH-depleted mice.
To provide an alternative to presently available subjective ways of measuring sperm motility which often yield inconsistent data, we devised a method for determining sperm motile efficiency with it one can express objectively the amount of active sperm movement. Using a melangeur for counting white cell, semen is diluted 20-fold in normal saline solution. With the diluted semen on Thoma's hemocytometer, spermatozoa passing its small quarter line in one minute are counted, and the value is divided by the estimated number of spermatozoa per ml. The quotient is multiplied by 100 and expressed by %/min. This shows the active movement of a spermatozoon per minute. In the present study, we measured sperm motile efficiency in 162 male sterility patients, 64 cases showed values of 49%/min or less, with a mean of 20.3%/min, 46, between 50%/min and 99%/min, with a mean of 70.1%/min; and the remaining 52 over 100%/min, with a mean of 195.9%/min. Among these there were 10 cases of successful pregnancy with a mean sperm motile efficiency of 152.7%/min, and 69.0%/min at the lowest. Our new method requiring no special equipment can easily identify active sperm movement and is easily reproducible,
The motility rate of sperm during capacitation process was determined by calculating a sperm motile efficiency index (SMEI) using a hemocytometer. The SMEI values for the sperm from 100% of normal fertile men and 64% of infertile patients increased significantly by the fourth hour of incubation, while for 36% of infertile patients there was no increase. A correlation between the increase of SMEI and original motility, original SMEI and original semen amount was not possible. In addition, a decrease of the SMEI value was observed after sperm incubated for 3 hours were added to the seminal plasma of the donor. It is concluded that in human spermatozoa "hyperactivation and dehyperactivation" can be measured by SMEI.
The effects of OK-432 (streptococcal preparation) on murine fulminant hepatitis were investigated. Hepatitis was induced by injection of mouse hepatitis virus type 2 (MHV-2) at a strength of either 1 x 10(3) or 1 x 10(4) plaque-forming units (PFU). Mice without OK-432 treatment died within 5 days, whereas mice preinoculated with OK-432 showed survival rates of 50% (1 x 10(3) PFU) or 10% (1 x 10(4) PFU) after 60 days. Survival time was not prolonged if OK-432 was injected after MHV-2. Examined histologically, mice not treated with OK-432 showed severe haemorrhagic necrosis of the liver, often panlobular. Treated mice showed less necrosis; the least necrosis was observed in those injected with OK-432 before MHV-3. In those mice injected first with OK-432 and then with 1 x 10(3) PFU of MHV-2 that survived 7 days, autopsy showed a very slight and focal hepatic necrosis, with follicular infiltration by lymphocytes and macrophages. Mitogenic reaction of spleen cells was remarkably less than normal in mice with MHV-2 injection. However, mice injected with OK-432 before MHV-2 (same treatment as mice showing high survival rates) showed relatively high reactivity in comparison with mice not treated with OK-432.
The in vitro lymphokine-activated killer (LAK) activity of peripheral blood mononuclear cells (PBMC) from 36 patients with hepatocellular carcinoma was investigated. The activity was greatly diminished in 13 patients and enhanced in seven patients. A flow cytometric study showed that the percentage of OKM1+, Leu-7+-11b+, and Leu-7-11b+ fractions in PBMC was decreased and the percentage of OKT8+ and Leu7+11- fractions was increased significantly in the 13 patients with lower LAK activity, compared with the values of the seven higher LAK activity patients. Furthermore, the response of PBMC to interleukin-2 (IL-2) was deficient in the lower activity group. However, there was no significant difference in IL-2 production by PBMC, IL-2 receptor (p55) expression of PBMC and mitogen (Con-A, PHA) response of PBMC between the two groups. These findings indicate the possibility that diminished LAK activity in hepatoma patients is due to a decreased number of LAK precursor cells and a defective response of LAK precursor cells to IL-2.
Electron microscopic studies of peripheral blood mononuclear cells (PBMC) in chronic type C hepatitis revealed several interesting structures after interferon-alpha (IFN-alpha) therapy. Fifteen of 20 patients were treated with IFN-alpha. Tubuloreticular inclusions (TRI) were observed in only one patient who did not receive therapy. In contrast, TRI were observed in 10 of 15 (66.7%) patients who underwent the therapy for 2 weeks to 6 months. Cylindric confronting cisternae (CCC) were identified in the cytoplasm of PBMC in 4 of 16 (25%) patients who underwent the therapy. CCC were found only after IFN-alpha therapy. The appearance of both TRI and CCC in the PBMC was significantly correlated to IFN-alpha therapy. Although there is little evidence about the morphogenesis of TRI and CCC, these structures may be a host response to IFN-alpha induced by hepatitis C virus infection.