Acta Medica Okayama volume41 issue2

The effects of seizure activity on the mossy fiber endings of El mice were studied by electron microscopy. During epileptic seizures of El mice, the number of clear round vesicles (50 nm) in the mossy fiber endings of the hippocampal formation decreased, while the number of large densecore vesicles (100 nm) increased. In these endings, the large dense-core vesicles were scattered during the resting state, but after seizure activity they tended to accumulate together and attach to the presynaptic membrane. Omega-shaped profiles, which seemed to be due to exocytosis of the large dense-core vesicles, were seen in the presynaptic membrane.

The analysis of bile acids in human bile was tried by high-performance liquid chromatography (HPLC). Bile acids in human bile were first prefractionated into free, glycine- and taurine-conjugated bile acids using a Seppak C18 cartridge and a piperidinohydroxypropyl Sephadex LH-20 (PHP-LH-20) column. Each fraction was then processed through a HPLC system consisting of a Zorbax ODS column and a 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) column. By these procedures the major 15 bile acids were clearly separated, and each bile acid of 10-125 ng was accurately analyzed. More than 400 times of analysis could be repeated on one 3 alpha-HSD column without loss of sensitivity. Thus the pretreatment through Seppak C18 and PHP-LH-20 made the HPLC analysis of human bile acids accurate and applicable to clinically obtained materials.

Antibody activity, especially that involved in the reaction of antibody-dependent cell-mediated cytotoxicity (ADCC), of five commercially available human gammaglobulin preparations (standard, pepsin-treated, plasmin-treated, polyethylene glycol-fractionated and S-sulfonated gammaglobulin) was measured. All these gammaglobulin preparations had high titers of hemagglutination inhibition and neutralizing antibody against measles virus. In ADCC reaction, the pepsin-treated gammaglobulin preparation showed no antibody activity. The standard gammaglobulin preparation showed weak activity only when highly diluted. The remaining three preparations showed high activity. Though the S-sulfonated gammaglobulin preparation showed no activity in ADCC reaction, it showed high activity after reconversion by means of oxidation and reduction in vitro. The plasmin-treated gammaglobulin preparation showed greater activity than the polyethylene glycol-fractionated preparation of the optimal concentration. In ADCC tests using the plasmin-treated gammaglobulin preparation, K cell activity was strongly inhibited by Hg (thimerosal), while, in those using the standard gammaglobulin preparation, the activity was hardly influenced by Hg, suggesting that the low ADCC activity of the standard gammaglobulin preparation of high concentrations was due to the inhibitory effect of aggregated immunoglobulin G molecules.

We administered serum fractions obtained from cancer patients by double-filtration plasmapheresis (DFPP) to cancer-bearing mice to examine the effects on tumor growth and metastasis. Fraction 1 (whole plasma), fraction 2 (a plasma fraction containing substances with higher particle size), fraction 3 (a plasma fraction containing substances with smaller particle size) and saline were administered intravenously to cancer-bearing mice for 10 days following the inoculation of tumor cells. The tumor growth and metastasis in mice administered fraction 2 was far more rapid than that in the control mice. On the other hand, tumor growth in mice administered fraction 3 was significantly delayed compared with that in mice injected with fraction 2. These results suggest that factors in the higher particle-size fraction of cancer patients' sera promote the growth and the metastasis of tumors in mice, and that DFPP, which remove these factors, is an effective therapy against cancer.

A clinical trial was performed to investigate the efficacy of hyperthermia in combination with chemotherapy for gynecological malignancies. Sixty-nine patients with vaginal or vulvar malignancies (9 primary vulvar, 3 recurrent vulvar, 11 primary vaginal, 4 primary cervical, 40 recurrent cervical, and 2 recurrent ovarian carcinomas) were treated by thermochemotherapy (42 cases) or chemotherapy alone (27 cases). After treatment, 7 patients underwent surgery and 46 patients irradiation. The chemotherapeutic schedule was mainly a combination therapy with bleomycin and mitomycin C (B-M). Microwaves of 2.45 GHz were applied to induce local hyperthermia. The side effects of chemotherapy were not increased by hyperthermia. The rate of partial response plus complete response increased to 84% (16/19) in primary cancers and 45% in recurrent cancers by hyperthermia, compared to the respective values of 40% (2/5) and 17% (3/17) for chemotherapy alone. However, a satisfactory prognosis cannot be expected with thermochemotherapy, unless additional treatments are performed. Subsequent surgery or radiation treatment improved the progression-free interval.

A significant amount of anticoagulant substance was released along with histamine, when human lung mast cells were stimulated with anti-IgE and Ca-ionophore A23187. Its activity was lost by heparinase, not by chondroitin-ABC lyase or chondroitin-AC lyase, and also inhibited by Polybrene, suggesting it would be heparin.