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Biomedical subjects

K Miyake

Publications and source records attributed to K Miyake.

At least 559 records · Page 31Linked to original sources

[Cerebroprotective action of naftidrofuryl oxalate. I: Prolongation of survival time and protection of cerebral energy metabolism in bilateral carotid artery-ligated mice].

The present study was designed to elucidate whether naftidrofuryl oxalate (LS-121) may exert a beneficial effect on survival time and cerebral energy metabolism of bilateral carotid artery (BCA)-ligated mice. Survival time of BCA-ligated mice ranged from 100 to 308 sec. Administration of 15, 45 and 100 mg/kg, i.p. and 100 mg/kg, p.o. LS-121 significantly prolonged the survival time. Cerebral adenosine triphosphate (ATP), creatine phosphate (CP) and glucose contents were markedly reduced at 2 min after BCA-ligation. Cerebral lactate content was increased by the ligation, whereas the pyruvate content was not altered. Pretreatment of mice with 15, 45 mg/kg, i.p. and 100 mg/kg, p.o. LS-121 suppressed BCA-ligation induced decrease in high-energy phosphates of the mouse brain. Ligation-induced decrease in glucose and increase in lactate content tended to be attenuated by the treatment with 45 mg/kg, i.p. LS-121. Time course of changes in metabolic variables altered by BCA-ligation with and without the pretreatment with 45 mg/kg, i.p. LS-121 showed a significant suppression of ligation-induced decrease in cerebral high-energy phosphates. The results suggest that LS-121 is beneficial for ischemic mouse brain energy metabolism, which may be related to the prolongation of the survival time.

Animals↗

[A study of postoperative adjuvant chemotherapy of advanced urinary epithelial cancer].

The effect of postoperative adjuvant chemotherapy was studied in 22 cases of advanced urinary epithelial cancer. Vincristine, mitomycin C and bleomycin (VMB) was administered in combination to 9 prophase cases from December, 1980 to March, 1982 and cis-dichlorodiamine platinum, peplomycin and mitomycin C (PPM) in combination to 13 anaphase cases from April, 1982 to November, 1984. The site was renal pelvic cancer in 3 cases, cancer of the ureter in 3 cases, cancer of the bladder in 13 cases, cancer of the pelvis, ureter, and bladder in 1 case, and recurrence of pelvic cancer following bladder cancer in 2 cases. The degree of invasion was pTa in 2 cases, pT1 in 1 case, pT2 in 1 case, pT3 in 11 cases and pT4 in 5 cases. Lymph node metastasis had occurred in 9 cases, no metastasis in 8 cases and it was unclear in the remaining 6 cases. The mean observation period was 16.5 months; 10 patients were alive without any tumors, one patient was alive with a tumor, 11 patients died of cancer, and one patient died intercurrently. The mean postoperative survival period in the mortality cases was 14.5 months. According to the classified type of chemotherapy received, there were 3 out of 9 cases (33.3%) who survived without tumors after receiving VMP and 7 out of 13 cases (53.8%) in the PPM group who survived without tumors. Although a simple comparison cannot be made, it appears that PPM therapy is superior. No severe side-effects were observed.

Aged↗

[Female urethral carcinoma: results of irradiation in 2 patients].

Urethral carcinoma in 2 females has been treated with irradiation together with adjunct chemotherapy. In case 1, a 73-year-old female with squamous cell carcinoma was successfully treated with irradiation of 4,000 rad and peplomycin of 60 mg intravenously given. She has been free from the disease for the past 43 months. In case 2, a 61-year-old female with transitional cell carcinoma was initially treated with irradiation of 5,000 rad together with peplomycin 90 mg, which was followed by another 5,000 rad irradiation. The tumor recurred and the patient was operated on for cystourethrectomy and partial resection of the vagina. A further chemotherapy of cisplatin, peplomycin, and mitomycin C was instituted. She died of the tumor recurrence 23 months after the first visit to our clinic. Diagnosis and treatment modalities on the female urethral carcinoma are briefly discussed.

Aged↗

[Multivariate evaluation of survival factors and postoperative adjuvant chemotherapy in patients with bladder cancer treated by radical cystectomy].

Multivariate analysis by Cox's proportional hazard model was performed on 71 bladder cancer patients treated by radical cystectomy to clarify factors affecting survival and to evaluate the efficacy of postoperative adjuvant chemotherapy. Clinicopathologic data included in the analysis were age, sex, interval from onset of symptoms to first consultation, prior tumor history, year of operation and tumor characteristics: size, number, growth pattern, stage, grade, mode of infiltration, lymphatic invasion, lymph-node metastasis and lymphocyte infiltration around tumors. Analysis revealed that stage is the most statistically significant factor for survival (p less than 0.0001); followed by year of operation (p less than 0.05) and lymph node metastasis (p less than 0.1). The above three determinants yielded hazard ratios of 16.6 for stage (pT3a-pT4 vs. pTis-pT2), 2.7 for year of operation (1978-1982 vs. 1983-1987) and 2.4 for lymph node metastasis (positive vs. negative). Postoperative adjuvant chemotherapy consisting of cisplatin, peplomycin and mitomycin C (PPM therapy) seemed to improve survival, when the influence of the major prognostic factors were adjusted by the proportional hazards model. The authors conclude that stage and lymph node metastasis should be considered when postoperative adjuvant treatment is selected for patients with bladder cancer treated by radical cystectomy, and that further prospective randomized trials are mandatory to confirm the efficacy of postoperative adjuvant PPM therapy suggested by the present retrospective multivariate analysis.

Adult↗

Cardioprotective action of alpha-blocking agents, phentolamine and bunazosin, on hypoxic and reoxygenated myocardium.

The present study was undertaken to determine whether alpha-blocking agents, phentolamine and bunazosin, may exert a cardioprotective effect on hypoxic and subsequently reoxygenated hearts. For this purpose, rabbit hearts were perfused for 20 min under hypoxic conditions, followed by a 45 min-reoxygenation. Agents were administered between the 8th and 20th min of hypoxic perfusion. Hypoxic perfusion for 8 min resulted in a decline of cardiac contractile force and myocardial high-energy phosphates and a loss of adenine nucleotide metabolites from the heart, whereas a rise in resting tension was not observed. Neither increase in perfusion pressure, release of creatine kinase from hearts nor increase in tissue calcium was observed. At 20 min-hypoxia, significant changes in resting tension and perfusion pressure of the heart and release of creatine kinase from the heart were observed. Cardiac contractile force after 45 min of reoxygenation was less than 10% of the initial value. Treatment with 83 microM phentolamine or 46 microM of bunazosin resulted in a significant suppression of hypoxia-induced increase in tissue calcium, release of creatine kinase and adenine nucleotide metabolites and rise in perfusion pressure and resting tension. Treatment with either phentolamine or bunazosin resulted in appreciable recovery of cardiac contractile force. Reoxygenation-induced release of creatine kinase was also suppressed significantly. Two possible mechanisms for the protective effect of this treatment are considered; 1) preservation of ATP metabolites which may be utilized as substrates for a salvage synthesis of ATP during reoxygenation and 2) prevention of a nonselective transmembrane flux of cellular constituents due to changes in cell membrane permeability.

Adenosine Triphosphate↗

[A morphological study of the testis in patients with idiopathic male infertility--quantification and ultrastructure of Leydig cells].

Testicular biopsy was performed on 51 patients with idiopathic male infertility and 13 normal fertile adults. The biopsied specimens were examined by light and electron microscopy. A quantitative evaluation of Leydig cell number was made by determining the mean number of Leydig cells per one cross section of seminiferous tubule in the entire histologic section of each specimen, which was defined as "Leydig cell index". In both oligospermic and azoospermic groups, the Leydig cell index was significantly elevated as compared with in that the normal group, which indicated the presence of Leydig cell hyperplasia in the infertile testis. In addition, this index significantly correlated with serum luteinizing hormone and follicle stimulating hormone levels but not with serum testosterone level. Leydig cells were classified into three types based upon their morphological characteristics. Type I Leydig cells were functionally active and mature ones, with a smooth-surfaced round or oval nucleus, had abundant smooth endoplasmic reticulum (SER), characteristic mitochondria and relatively few lysosomes. Type II Leydig cells were functionally less active, and contained an irregularly shaped nucleus, less abundant SER, mitochondria with undeveloped cristae and relatively few lysosomes. Type III Leydig cells included immature and regressive cells, which were considered to have almost no hormone secreting function. The immature Leydig cells were spindle-shaped and had few cell organelles. The regressive cells had poorly developed SER and many secondary lysosomes in the cytoplasm. In the normal group, type I Leydig cells are the most numerous but in the infertile groups type II Leydig cells are the most numerous. However, in the latter, there is no significant difference in relative number of each Leydig cell type among the groups classified according to the number of sperm or Leydig cell. In summary, Leydig cell hyperplasia observed in the testis of the infertile patients was supposed to be induced by the elevation of the serum LH. Despite of the significant increase in Leydig cell number, the serum testosterone was not elevated, and this was considered to be due to the fact that the hyperplastic cells are mainly composed of functionally less active type II Leydig cells. In addition, especially in the severe hyperplastic group, not only type II but also type I Leydig cells increased in number. However, in this group, the serum testosterone level was not elevated. Therefore, the function of type I Leydig cells was suggested to be impaired.

Follicle Stimulating Hormone↗

Synthesis of prostaglandin E in rabbit eyes with topically applied epinephrine.

Using radioimmunoassay techniques, we measured the amounts of prostaglandin E (PGE) in the aqueous humor and vitreous body of 22 phakic and ten aphakic rabbit eyes. Either epinephrine and placebo, epinephrine and indomethacin, indomethacin and placebo, or placebo and placebo were administered topically for 5 months. Treatment of aphakic eyes was initiated 1 month after intracapsular lens extraction. Topically applied epinephrine apparently induced the synthesis of prostaglandin, manifested by elevated PGE in the aqueous and vitreous. Phakic eyes treated with epinephrine and placebo had mean PGE levels of 407.33 pg/ml in the aqueous and 177.0 pg/ml in the vitreous, whereas control eyes given only placebo had mean levels of 165.83 in aqueous and 59.17 in vitreous. Topically applied indomethacin inhibited epinephrine-induced synthesis of PGE in the aqueous humor, but had no significant effect in the vitreous. PGE levels, higher in placebo-treated aphakic eyes than in phakic ones, were elevated further by epinephrine treatment (from 388.40 to 1851.60 pg/ml in aqueous of aphakic eyes, and from 236.40 to 850.60 pg/ml in vitreous also of aphakic eyes). Our findings relate to the pathogenesis of epinephrine-induced maculopathy and to the mechanism of the ocular hypotensive effect of epinephrine.

Administration, Topical↗

Role of ATP metabolites in induction of incomplete recovery of cardiac contractile force after hypoxia.

The present study was designed to elucidate metabolic factors related to reoxygenation-induced recovery of cardiac contractile force after a period of hypoxia, from the view point of energy metabolism in the myocardium. Rabbit hearts were perfused for 20 mins under various degrees of hypoxic conditions, followed by 45 mins of reoxygenation. Hypoxia induced a rise in resting tension, a cessation of cardiac contractile force, a depletion of high energy phosphates, an increase in tissue calcium and an increase in UV absorbance of the perfusate. High performance liquid chromatography analysis of the perfusate indicated that the increase in UV absorbance of the perfusate was attributed to the release of ATP metabolites from the perfused heart. Reoxygenation-induced recovery of cardiac contractile force after 20 mins of hypoxia was predicted by the degree of the rise in resting tension at the final period of hypoxia. The recovery was related to the level of high energy phosphates in the reoxygenated heart as well as the loss of ATP metabolites from the heart but not to the tissue calcium content. The loss of ATP metabolites also correlated with myocardial ATP levels at 45 mins of reoxygenation and a rise in resting tension at 20 mins of hypoxia. The results suggest that loss of ATP metabolites is a vital step in the induction of incomplete recovery of cardiac contractile force after hypoxia.

Adenosine Triphosphate↗