Kaoru Sekiba

Clinical evaluation of schizophyllan combined with irradiation in patients with cervical cancer: A randomized controlled study

To evaluate the clinical effects of the anti‐tumor polysaccharide Schizophyllan (SPG), a randomized study was done on 220 patients with Stage II or Stage III cervical cancer who had been given irradiation, concomitantly. The tumor‐reducing effect of SPG was significant in patients in either stage. The time to recurrence was longer in SPG‐dosed patients with Stage II cancer, compared with findings in the control group. There was no significant difference in the time to recurrence in patients with Stage III cancer between the SPG and control groups. When comparing the 48‐month survival curve, the survival time of patients with Stage II cancer in the SPG group was significantly longer than in the control group. However, there was no significant difference in the survival rate of patients with Stage III cancer between the SPG‐ dosed and control groups.

Changes of lipid peroxidation and superoxide dismutase activity in the human placenta

The oxygen radical may induce peroxidation of unsaturated fatty acids in vivo. We studied changes in superoxide dismutase (SOD) activity and lipid peroxidation using human placental tissue. Lipid peroxidation was marked in early stages (2 to 4 months) of gestation but decreased with growth and was very small by the end of pregnancy. The SOD activity of placental tissue in early gestation was approximately 250 to 500 U per gram of wet weight. The activity increased with growth of the placenta and reached a level of 400 to 1,500 U per gram of wet weight by the end of gestation. These results for SOD activity suggest that the oxygen requirement in the placenta at early stages of gestation is low compared with that at the end of gestation.

Superoxide Dismutase Activity and Lipid Peroxidation of the Rat Liver during Development

The present work was an attempt to understand the effects of oxygen toxicity in the early neonatal period and was performed using rat liver homogenate and mitochondria as examples of superoxide dismutase (SOD) activity and lipid peroxidation. SOD activity of the liver was extremely low during the fetal period and approximately the 5th day after birth. However, a rapid increase in the level of activity was observed from about the 10th day after birth. By the 20th day, this had reached 88% of the level in the adult rat. Peroxidated lipids, in an inverse relation to SOD activity, occurred at high levels during the fetal and early neonatal period, but rapidly decreased after the 10th day. It can be considered, therefore, that protection against oxygen toxicity is inadequate in such rat livers during the fetal and early neonatal periods, but that it is well established by the 10th day after birth.

Clinical evaluation of sizofiran combined with irradiation in patients with cervical cancer. A randomized controlled study; a five-year survival rate.

Following a previous report [1] we ascertained the effectiveness of sizofiran (Schizophyllan:SPG) to prolong the survival and time to recurrence of the patients with Stage II or III cervical cancer, as evaluated in a 5-year randomized controlled study conducted in 19 institutions in Japan.Of the overall patients with Stage II or III cancer, time to recurrence and survival rate in the group on SPG were significantly longer than in the control group. In the Stage II patients, there was significant difference in time to recurrence, and survival of SPG group tended to be longer than that of the control group. However, in the Stage III patients, there was no significant difference in either time to recurrence or survival rate.

Determination of tryptophan and its metabolites in human plasma and serum by high-performance liquid chromatography with automated sample clean-up system

An automated high-performance liquid chromatographic method that incorporates direct injection of biological samples followed by chromatographic sample clean-up in a precolumn is described for the determination of tryptophan and its metabolites in human plasma and serum. The system gave reproducible data with a coefficient of variation of less than 3% with a sample size of 100 microliters of human plasma. The major tryptophan metabolites found in 100 microliters of human plasma were kynurenine, indolelactic acid, indoleacetic acid, indolepropionic acid, serotonin and 5-hydroxyindoleacetic acid. The level of tryptophan and kynurenine in individuals was constant in comparison with other metabolites. Analysis of samples from normal controls, diabetics, gravida and their foetuses showed a tendency for tryptophan metabolites to be low in maternal plasma.

Urinary and Plasma Epidermal Growth Factor Levels Are Decreased in Neonates with Intrauterine Growth Retardation and in Their Mothers

Epidermal growth factor (EGF) concentrations in urine and plasma samples collected from pregnant women and neonates were measured by RIA. The EGF concentration of the first voided urine was higher in appropriate-for-date (AFD) neonates (33.9 +/- 23.0 ng/mg creatinine) than in those with intrauterine growth retardation (IUGR; 23.5 +/- 7.7 ng/mg creatinine, p less than 0.05) and heavy-for-date (19.8 +/- 5.2 ng/mg creatinine, p less than 0.05) neonates. The urinary EGF concentration of pregnant women showed no marked changes throughout pregnancy. Urinary EGF concentrations of women with AFD fetuses (45.9 +/- 31.2 ng/mg creatinine) did not differ significantly from those of women with diabetes (39.9 +/- 26.8 ng/mg creatinine) or women with multiple fetuses (44.6 +/- 30.6 ng/mg creatinine). However, women with IUGR fetuses showed lower urinary EGF concentrations (13.8 +/- 7.4 ng/mg creatinine, p less than 0.05) than women with AFD fetuses. Maternal and fetal platelet-poor plasma EGF concentrations at delivery were lower in the IUGR group (mother: 2.62 +/- 0.38 ng/ml, fetus: 2.16 +/- 0.07 ng/ml, respectively, p less than 0.05 and p less than 0.005) than in the AFD group (mother: 3.34 +/- 0.64 ng/ml, fetus: 3.24 +/- 0.93 ng/ml). In the IUGR group, the EGF concentration in fetal blood was always lower than that in maternal blood (p less than 0.05), although the AFD groups showed no such difference. These data suggest that EGF levels are closely related to fetal growth.

Immunotherapy using the streptococcal preparation OK-432 for the treatment of uterine cervical cancer. Cervical Cancer Immunotherapy Study Group.

The effectiveness of immunotherapy using a streptococcal preparation, OK-432, was evaluated for cervical cancer. The 382 eligible patients were stratified by presence/absence of surgical operation and clinical stage, and then, in each stratum, were randomly divided into two groups: an OK-432 treatment group and a control treatment group. The 3-year recurrence-free rates of 221 patients in the OK-432 group and 161 patients in the control group were 71.9% and 58.6%, respectively. The intergroup difference was statistically significant (P less than 0.05). Delayed skin reactions to phytohemagglutinin (PHA) and Su-polysaccharide extracted from Streptococcus pyogenes Su-strain (Su-PS) and peripheral lymphocyte counts were reduced within two months after the initiation of therapy in both groups. The observed immunological changes were apparently reversed by 3 months after the start of the therapy in the OK-432 group, but this took at least one year in the control group, with significant intergroup differences at 6 and 12 months of the therapy (P less than 0.01). These results indicate that OK-432 can be considered as one of the most effective and useful immunotherapeutic agents for cervical cancer.

Automated direct assay system for the measurement of sex steroid hormones in serum using high-performance liquid chromatography

An automated direct assay system using high-performance liquid chromatography was developed for the simultaneous measurement of estradiol, estrone, progesterone, 17 alpha-hydroxyprogesterone, 20 alpha-hydroxyprogesterone, testosterone and androstenedione in biological fluids. A comparison between the values measured by this method and by radioimmunoassay revealed good correlation for estradiol (r = 0.938, p less than 0.001) and progesterone (r = 0.903, p less than 0.001). Estradiol and estrone could be analysed above the level of 250 pg/ml, and progesterone, 17 alpha-hydroxyprogesterone, 20 alpha-hydroxyprogesterone, testosterone and androstenedione could be analysed above the level of 5.0-7.5 ng/ml. The method was applied to the clinical appraisal of placental function and maturation of ovarian follicles.

Lipid Peroxidation and Antioxidants in the Rat Lung during Development

The extent of lipid peroxidation and the levels of its antioxidants such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) were determined on lung tissues of the fetal, newborn and adult rat. Lipid peroxide formation was slight in the fetal period but augmented after birth reaching a peak at about 10 days after birth. The peroxide concentration then gradually declined with development and the adult level was found comparable to the fetal level. In the examination of the developmental defensive mechanism on the basis of assays for the aforementioned antioxidant enzymes in lung tissue, the SOD activity was low in fetuses reaching approximately 90% of the adult level at 10 days of life. Catalase was extremely low in concentration at all times, and age-related variations could not be definitely obtained. GSH-Px was also measured low in the fetal period and during 20 days after birth, but a subsequent gradual rise resulted in threefold greater activity in adults than in fetuses.

Effect of Guanidinoethyl Sulfonate on Taurine Concentrations and Fetal Growth in Pregnant Rats

Guanidinoethyl sulfonate (GES), a transport antagonist of taurine, was given to pregnant rats from day 11 to 21 of gestation as a 1% solution in drinking water. On day 21 of gestation in GES-treated pregnant rats, the concentration of taurine markedly decreased in the fetal whole body (54% of the control), the fetal liver (37%), the fetal whole brain (87%), the placenta (32%), the maternal liver (33%), the maternal whole brain (32%), and the maternal plasma (46%). The wet weight of fetal whole body, liver and brain of fetus, and placenta also showed a significant drop. But there were no differences of weight gain, in the liver and brain weights of the mother of the control and GES-treated pregnant rats. The urinary excretion of taurine in pregnant rats treated with GES was much higher than that of the controls. These results suggest that the administration of GES to pregnant rats induces much urinary taurine excretion with a resulting decrease in the tissue taurine content and readily produces taurine-deficient fetal rats.