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Biomedical subjects

M Miyazaki

Publications and source records attributed to M Miyazaki.

At least 901 records · Page 50Linked to original sources

[Combined therapy with polyamine biosynthesis inhibitors and mitomycin C].

An attempt was made to analyse tumor growth after cessation of combined therapy with the polyamine biosynthesis inhibitors, alpha-difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG), as well as mitomycin C (MMC). DFMO 1000 mg/kg, MGBG 50 mg/kg and/or MMC 2 mg/kg were given intraperitoneally to BALB/c nu/nu mice xenotransplanted human gastric cancer, and its growth as well as DNA biosynthesis were measured daily, after cessation of these combined treatments. Histological observation of the tumor was also performed by hematoxylin-eosin staining. The combination with DFMO and MGBG stunted tumor growth during the treatment, but 3 days later its growth and DNA biosynthesis were accelerated distinctly. MMC injection halted tumor growth, and 5 days after termination of MMC injection its growth rate and DNA biosynthesis almost completely recovered. The microscopic findings on the 4th day after termination of MMC injection were similar to those of DFMO + MGBG treatment. The combination DFMO, MGBG and MMC suppressed not only tumor growth during the treatment, but also tumor growth and DNA biosynthesis over 7 days. The histologic observation 4 days later revealed extensive damage.

Animals↗

[Experimental studies on hepatic cancer chemo-embolization].

Mitomycin microspheres (MMC MS), which contain about 5% of MMC and have an average diameter of 45 +/- 8 microns, were administered into the rat hepatic artery in a preclinical study on antitumor treatment for human hepatic cancer. Plasma GOT and GPT activities increased markedly 24 hours after MMC MS injection; they decreased to within the normal range within 3 days of the injection. Hepatic necrobiosis was observed in the area adjacent to the hepatic arterioles containing MMC MS, but was not observed in rats injected with placebo microspheres. The hepatic vein blood of MMC MS treated rats contained a markedly high level of MMC, compared to rats treated in the conventional fashion with MMC. Furthermore, MMC MS remained within hepatic arterioles for over 3 weeks.

Alanine Transaminase↗

[Experimental hyperthermo-chemotherapy for human gastric carcinoma transplanted in the nude mice].

Human gastric carcinomas serially xenotransplanted into BALB/c nu/nu mice were treated by hyperthermo-chemotherapy with mitomycin C (MMC). The antitumor efficacy was assessed by both single and double treatments of 25-minute hyperthermia (43.5 degrees C) and/or 2.0 mg/kg of MMC (ip). Tumor weight was estimated using Battelle's Columbus Laboratories protocol. To assess DNA biosynthesis in the tumor cells, the xenotransplanted tumors were excised at prescribed times after these treatments 60 minutes after 3H-thymidine injection (ip), and were examined microscopically. In the group treated twice by hyperthermo-chemotherapy marked growth inhibition and microscopic damage of the tumors were observed, while such features were not recorded in groups treated twice by hyperthermia only and chemotherapy only, nor in groups given single hyperthermo-chemotherapy, or hyperhermia and chemotherapy. In the single-treated groups, DNA biosynthesis was remarkably inhibited by hyperthermo-chemotherapy over 24 hours. The present results suggest that repeated treatments of hyperthermo-chemotherapy with MMC may be effective in the treatment of human gastrointestinal cancer.

Animals↗

Poly(U)-dependent polyphenylalanine and polytyrosine synthesis in vitro by a tRNATyr variant with an enzymatically altered anticodon, G-A-A.

A variant of T. utilis tRNATyr containing a base substitution (psi----A) in the middle position of the anticodon has been constructed by enzymatic procedures in vitro. This variant is unique in that it can accept both tyrosine and phenylalanine. This tRNA was shown to be active in transferring both tyrosine and phenylalanine into polypeptides in a cell-free, poly (U)-directed translation system from yeast. This result gives further support to the adapter hypothesis since tyrosine, attached to the variant tRNATyr with an anticodon G-A-A, is incorporated into polypeptides in response to poly (U) message.

Anticodon↗

[Diaphragm pacemaker implantation: a case report of central hypoventilation due to cerebellar bleeding].

A 60-year-old male developed chronic respiratory failure due to central hypoventilation after cerebellar bleeding. We implanted a diaphragm pacemaker (radio-frequency type) to the patient, and his respiratory status was improved. Although this apparatus devised by Glenn has been widely used in the United States, clinical applications in Japan were rarely reported. Diaphragm pacing might be one of the effective treatments to the patient with chronic respiratory failure. We discussed the indication, mechanical subject and surgical approach concerning diaphragm pacemaker implantation in this paper.

Cerebellar Diseases↗

[Electron microscopic study of an experimental contusion cataract of a Japanese monkey].

The traumatic cataract was experimentally induced in the lens of a Japanese monkey and observed with the electron microscope. The purpose of this study was to shed some light on the origin of the cataract caused by various factors. The clinical examinations of the experimental animal showed the opacity of the posterior subcapsular cortex. Electronmicroscopic investigations revealed that lens fibers within the opaque region increased in number of mitochondrion, rough surfaced endoplasmic reticulum and other organelles when compared with those in the clinically normal region of the lens. Furthermore, the intercellular space in the opaque region increased to such an extent that large extracellular vacuoles were formed. Many of these lens fibers became swollen and decreased the interdigitation. Some swollen cells showed sparse arrangement of their cytoplasmic filaments. These morphological changes showed an acceleration of water absorption of the lens fibers from a relatively early stage of the traumatic contusion cataract. The increase in number of mitochondrion in such swollen (hydropic) fibers may play an important role in this process. The present experiment suggests that the appearance of so-called hydropic cells is an initial change in the cataractous lens.

Animals↗

Expression of gamma-glutamyltranspeptidase in cultures of spontaneously and chemically transformed rat liver cells.

The expression of gamma-glutamyltranspeptidase (gamma-GTP) and the relationship between this enzyme activity and tumorigenicity were studied in 38 tumorigenic and non-tumorigenic epithelial cell lines derived from livers of normal and aminoazo-dye-fed rats. Nine of 22 non-tumorigenic epithelial cell lines exhibited gamma-GTP-positive cells, whereas 9 of 16 tumorigenic epithelial cell lines did not exhibit gamma-GTP-positive cells. This finding revealed that no correlation existed between the acquisition of gamma-GTP activity and tumorigenicity. None of 10 spontaneously transformed epithelial cell lines, which consisted of 8 tumorigenic and 2 non-tumorigenic cell lines, exhibited gamma-GTP-positive cells. On the other hand, 16 of 28 transformed epithelial cell lines, which were derived from aminoazo-dye-fed rat livers and aminoazo-dye-treated cultures of normal rat liver cells, included gamma-GTP-positive cells in various percentages. As described above, in contrast to in vitro spontaneous transformation of rat liver cells, it is obvious that the carcinogen-induced transformation of rat liver cells in vitro as well as in vivo was frequently accompanied by the acquisition of gamma-GTP-activity. Therefore, it is concluded that the expression of gamma-GTP in liver cells may be mainly associated with exposure to chemical carcinogens.

Animals↗

Hyperthermochemotherapeutic in vivo isolated perfusion of the rat liver.

This report describes a system of in vivo isolated perfusion of the rat liver. The effects of perfusion with 5-fluorouracil (5-FU) (0.125-1.5 g/kg) on survival, liver function, and hepatic regeneration are studied. A dose of 0.125-0.25 g/kg of 5-FU produced acceptable toxicity with 0% and 25% mortality rate, but induced liver dysfunction indicated by abnormal biochemical values and severe inhibition of hepatic regeneration. Doses of 0.5 g/kg, 1.0 g/kg, and 1.5 g/kg produced a mortality of 60%, 100%, and 100%, respectively. Regional hyperthermia (37-43 degrees C) achieved by perfusion of the liver with heated saline produced an adverse effect on survival, liver function and hepatic regeneration, which are both temperature- and perfusion time-dependent. Hyperthermochemotherapy using in vivo isolated hepatic perfusion might be acceptable for the treatment of unresectable liver cancer, but should not be utilized as an adjuvant therapy prior to hepatic resection without the use of hepatic growth factors which could reverse the inhibitory effect of hepatic perfusion.

Alanine Transaminase↗

Clinical evaluation of prolonged chemotherapy combined with induction of hepatic drug-metabolizing enzymes as an adjuvant for treating patients with gastric cancer.

A clinical trial of a protracted adjuvant cancer chemotherapy was carried out on 207 patients with operable gastric cancer, from April, 1977, in the First Department of Surgery, Chiba University Hospital and two closely related hospitals. These patients were given intravenously 0.4 mg/kg and 0.2 mg/kg of mitomycin C on the day of operation and the next day, respectively, and then 16 mg/kg intravenously of Futraful (FT-207) daily from the 10th postoperative day until discharge, followed by oral administration of FT-207, 12 mg/kg, for 24 to 36 months after discharge. Two mg/kg of phenobarbital and 30 mg/kg of glutathione were administered randomly to half the number of patients (induction group) to induce hepatic drug-metabolizing enzymes. Significantly higher levels of serum 5-Fluorouracil (5-FU) released from FT-207 were found in the induction group than in the controls. Five-year overall survival rates in the induction and control groups revealed no difference. However, the survival rates in Stage III patients in the induction group were significantly superior in the 3-5 postoperative years, compared to those in the Stage III of the control group, while Stage I, II and IV patients apparently received no benefit from this induction treatment.

Clinical Trials as Topic↗

Protection of thermochemotherapeutic-induced lethal acute hepatic necrosis in the rat by 16,16-dimethyl prostaglandin E2.

These studies further evaluate the hepatocytoprotective properties of 16,16-dimethyl prostaglandin E2 (dmPGE2) by assessing its effect on survival, liver function, and hepatic regeneration in a model of in vivo isolated perfusion of the rat liver with high concentrations of cytotoxic drugs and regional hyperthermia. Isolated perfusion with 1.0 g/kg of 5-FU or hyperthermia of 41 degrees C X 10 min resulted in 90-100% mortality in control rats, with extensive, patchy necrosis and infarction on histologic examination, and markedly elevated levels of SGOT and SGPT at 24 hr after perfusion. Pretreatment with dmPGE2 (10 micrograms/kg sc) at 30 min before, and at 6 and 24 hr after hepatic perfusion significantly improved survival to 80% (P less than 0.01) following 5-FU perfusion and to 40% (P less than 0.05) following hyperthermic perfusion. Animals were followed for at least 21 days after perfusion and demonstrated normal liver histology, dmPGE2-treated rats demonstrated significantly lower SGOT and SGPT levels at 24 hr after perfusion. dmPGE2 (2 micrograms/kg sc) given as above improved the length of time of survival but eventual mortality was not significantly improved. Oral administration (50 micrograms/kg po at 30 min before, 6 and 24 hr after perfusion) and posttreatment (10 micrograms/kg sc at 1, 6, and 24 hr after perfusion) had no significant effect on survival. Hepatic regenerative capacity following partial hepatectomy was severely suppressed following isolated hyperthermochemotherapeutic hepatic perfusion. Pretreatment with dmPGE2 (10 micrograms/kg sc) restored the DNA synthetic response in perfused rats to that seen in normal control rats after partial hepatectomy (P less than 0.05 and P less than 0.01). The results from these studies further confirm the role of dmPGE2 as a hepatocytoprotective agent and suggest potential clinical application in situations where there has been deliberate, therapeutic insult to the liver.

16,16-Dimethylprostaglandin E2↗

Controlled trial of thyrotropin releasing hormone tartrate in ataxia of spinocerebellar degenerations.

The clinical efficacy, dose-response relationship, and safety of TRH-T (thyrotropin releasing hormone tartrate) were assessed in 290 patients with spinocerebellar degeneration (SCD) in a 2-week, double-blind study using placebo as control. 254 patients satisfied the criteria for inclusion in evaluation of the drug efficacy. The patients were treated with TRH-T in an intramuscular dose of 2 mg, 0.5 mg or 0 mg (placebo) as TRH once a day for 2 weeks. Clinical responses to these treatments were evaluated 3 times: at the end of weeks 1 and 2 of treatment and a week after the end of treatment. The results of "global improvement rating" as well as those of "ataxia improvement rating" showed that both 2 mg and 0.5 mg TRH-T treatments were significantly superior to placebo treatment in patients with predominantly cerebellar form of SCD. The effect was well maintained a week after the end of the 2-week treatment in the patients who were given TRH-T in daily dose of 2 mg and showed improvement at the end of treatment. The results of "improvement rating of each symptom" revealed that 2 mg treatment was significantly more effective than placebo for disorders of standing, gait, speech and writing. In the patients who had no pyramidal involvement or disorder of deep sensation, the drug efficacy and dose-response relationship were evident. Adverse reactions to the drug such as headache, feeling febrile and nausea were observed in 50% of the patients on 2 mg treatment, in 38% of those on 0.5 mg treatment and in 21% of those on placebo patient, however, discontinued treatment because of adverse reactions.

Adult↗