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Biomedical subjects

M Seki

Publications and source records attributed to M Seki.

At least 433 records · Page 24Linked to original sources

Concanavalin-A-induced suppressor cell activity in idiopathic membranous nephropathy.

Suppressor cell activity (SCA) was analyzed in 8 patients with idiopathic membranous nephropathy (MN) and in 11 patients with chronic proliferative glomerulonephritis (CGN). We have assessed the ability of peripheral blood lymphocytes (PBL) stimulated by concanavalin A (Con A) to inhibit the proliferative response on normal allogenic lymphocytes by both Con A and phytohemagglutinin (PHA). It was found that the MN patients with nephrotic syndrome (NS) had significantly increased levels of suppression index (SI) when compared to the values obtained with normal controls. In contrast, the mean suppression values in the PBL from MN patients in remission and CGN patients with or without NS, whether the mitogen used was Con A or PHA, were similar to those of the control subjects. Thus, the majority of MN patients wih NS demonstrated an alteration in Con-A-induced SCA. The possible significance of these phenomena in the pathophysiology of MN is discussed.

Adult↗

Acute and subacute toxicity studies on collagen wound dressing (CAS) in mice and rats.

Single administration of collagen wound dressing (CAS) made from bovine derm in the form of finely ground powders was given to mice and rats via i.p., s.c. and p.o. routes and via i.v. route in the form of physiological saline extracts and it was continuously injected into mice for 28 days via s.c. route to study its acute and subacute toxicity. Examinations were made of on general conditions, body weight, food and water consumption, hematology, serum biochemistry, organ weight, and gross and microscopic findings. Results showed no marked toxicity except for local irritation which was seen only after parenteral administration. We concluded on the basis of these animal experiments that there should be no problem in regard to safety after somewhat more extensive therapeutic application of CAS as a wound dressing in clinical practice.

Animals↗

HB Handa [alpha 90 (FG 2) Lys replaced by Met]: structure and biosynthesis of a new slightly higher oxygen affinity variant.

Hb Handa, an abnormal hemoglobin which isoelectrofocused anodally to Hb A, was found in a 15-year-old Japanese girl and her mother, who were apparently healthy. Clinical and hematological examinations showed no abnormality in individual heterozygous for this mutant gene except for a slight increase of reticulocyte count (2.1-2.4%). Structural studies disclosed an alpha chain anomaly and substitution of alpha 90 (FG 2) Lys replaced by Met. The content of the abnormal hemoglobin in the hemolysate was 17.5-18.3% of the hemoglobin. The isopropanol precipitation test was negative. The purified abnormal hemoglobin showed a slightly higher oxygen affinity than that of Hb A, but Hill's n constant, Bohr effect and organic phosphate effect were within the normal range. Globin chain biosynthesis in reticulocytes indicated that the production rate of the abnormal alpha chain was suppressed to 38% of the normal level.

Adolescent↗

Perinatal changes of alpha-fetoprotein concentration in the serum and its synthesis in the liver of analbuminemic rats.

The profile of appearance of disappearance of alpha-fetoprotein (AFP) in the serum of analbuminemic rats, which have a genetically controlled lack of serum albumin, was studied. During the perinatal stage, AFP was present in the serum of analbuminemic rats, its concentration at birth being 10 mg/ml as in normal rats. In analbuminemic rats, the concentration of serum AFP remained at about 10 mg/ml during the first week after birth and then decreased rapidly during the next 2 weeks, becoming undetectable about 4 weeks after birth. In normal rats, the serum AFP concentration reached a maximum of 11.5 mg/ml at birth and then decreased sharply to an undetectable level within 4 weeks after birth, although a small rebound of AFP concentration was observed about 1 week after birth. AFP synthesis in analbuminemic and normal rats was examined by injecting [3H]leucine i.p. and then measuring the radioactivity incorporated into the acid-insoluble fraction and immunoprecipitable fraction using anti-AFP antiserum. In analbuminemic rats, synthesis of AFP amounted to 7.5% of the total protein synthesis at birth and was maintained at about 7% of the total for the first week after birth and then decreased to 2% at 2 weeks after birth. In normal rats, AFP synthesis also amounted to 7.5% of the total protein synthesis at birth but decreased to about 2% at 2 days after birth and then remained at a low level for about 2 weeks. In both normal and analbuminemic rats, AFP synthesis was undetectable at 4 weeks after birth. These data show that AFP synthesis is shutoff after birth irrespective of the serum albumin concentration during neonatal development.

Animals↗

[Evaluation of pre-operative chemotherapy using FT-207 suppositories combined with glutathione--with special reference to histopathological antitumor effect].

Thirty patients with gastric cancer were clinically studied by rectal administration of FT-207 suppository at a dose of 1500mg per day as a preoperative adjuvant chemotherapy. Eighteen of thirty patients were divided into two groups, 13 patients of which were only administrated with tegafur (FT-207) suppository (Group A) and 5 patients were administrated with glutathione (GSH) at a dose of 1200mg daily with FT-207 suppository (Group B): The tissue concentration of FT-207 and 5-FU in normal and cancer tissues was measured following the resection of the stomach. In addition, we studied anticancer effect of FT-207 suppository on the basis of our original pathological criteria. Experimental results revealed that 5-FU concentration in serum was reached to maximum at 3 to 4 hours following administration in both groups. The serum concentration in most cases of the former group was decreased to the lower level of the effective concentration for 8 hours, however the latter could be kept the effective concentration for more than 10 hours. The correlation between the tissue concentration and total dose was analyzed. 5-FU concentration, which was active substance of FT-207, in cancer tissue was higher than in normal one, especially in Borrmann II type cancer, but the difference of concentration was not found between group A and B. The correlation between total dose and anticancer effect was also analyzed. Histopathological effect in group A showed a mild change, such as necrosis of cancer nest. On the other hand, group B revealed a markedly effective change like scarring formation. As the result, administration of FT-207 suppository with GSH was clinically and histopathologically effective procedure as preoperative adjuvant chemotherapy.

Antineoplastic Agents↗

[First results of in vitro fertilization in the human (author's transl)].

In vitro fertilization was studied in human egg cells obtained by laparoscopy. In 1979 our studies included 65 women with long term infertility and proven tubal factor infertility. The primary diagnostic laparoscopy established disease of uterus, tubes and ovaries and was used to correct pathology. Lysis of adhesions was used to make aspiration of a spontaneous mature follicle for in vitro fertilization easier. The aspiration laparoscopy was performed after stimulation with HMG and HPG. Our prerequisite was the presence of at least one ovary with ovulatory cycles. In almost all cases the ovaries wer accessible only following lysis of ovarian and tubal adhesions. Aspiration of the follicle was successful in 55 of the patients stimulated with HMG/HCG. In 10 cases no follicle for aspiration was available. In 21 cases one egg cell was found. In 11 cases more than one egg cell was found. The maximum was 8 egg cells in one patient. In 34 patients only cumulus cells were aspirated following stimulation. Under the in vitro fertilization conditions described in this paper it was possible to obtain twice a pro-nucleus formation, twice the two cell and twice the four cell stage following conjugation with sperm of the partner. Of the 47 patients with a tubal occlusion, 30 were isthmic or utero-isthmic and 17 tubal occlusions were peripheral. In 15 patients chromo-tubation showed recanalization.

Chorionic Gonadotropin↗

[Application of flow cytometric analysis to brain tumor chemotherapy. Report 1: Changes of cell kinetics induced by anticancer drugs (author's transl)].

It has been reported that flow cytometric analysis offers good indicators to select drugs for chemotherapy of malignant neoplasms, however, there are still few reports to try to apply these data to clinical treatment. For this purpose perturbation of cell cycle traverse which induced by several anticancer drugs was studied to determined the fundamental factors to indicate the sensitivity of each drugs. Results were: 1) Drugs showed high efficiency of accumulation of cells in SG2M phase even in low concentration; MMC, AD, CQ. 2) Drugs showed high efficiency of accumulation of cells in SG2M from low concentration high concentration; Vincristine. 3) Drugs which showed accumulation of SG2M in high concentration; ACNU, BCNU. 9L rat glioma cells treated with BCNU showed high efficiency of accumulation of cells in SG2M phase. In this cell line cytocidal effect was high. However, C6 cells which showed low accumulation in SG2M even by treatment with high concentration of BCNU revealed quite resistant to anticancer drugs from nitrosourea derivatives (ACNU, BCNU). Cytocidal effect of MMC and ACNU on C6 glioma cells was studied by colony forming efficiency assay using multicell spheroids treated with these drugs and it was discussed the correlation between percent of accumulated cells and cytocidal effect of each drug.

Animals↗

[Biosynthesis of steroids by human fetal kidney perfused in vitro (author's transl)].

In the present experiments, human fetal kidneys obtained from two fetuses aborted at mid-term (gestational age 21 weeks) were perfused in vitro with labeled precursor including 14G-dehydroepiandrosterone (DHA) and 14C-dehydroepiandrosterone-sulfate (DHA-S). Radioactive metabolites extracted after the termination of perfusion from the perfusate and the tissue were separated the free fraction by ether and conjugate fraction by n-butanol. Furthermore, recovery of the radioactivities were separated and purified by thin layer chromatography. Radiochemical purity of the metabolites were achieved by recrystallization to constant specific activity. When DHA was used as a precursor, in the perfusate, DHA-S, delta 5-Androstenediol, delta 5-Androstenetriol were identified as the metabolites derived from DHA, and they were successively recrystallized. But, when DHA-S was used as a precursor, the radioactive purity of the metabolite was not obtained. The result of this perfusion studies demonstrate a powerful activity of steroids sulfokinase and a slight activity of steroids 16 alpha-hydroxylase, 17 beta-hydroxysteroid dehydrogenase in fetal kidney.

Aryl Hydrocarbon Hydroxylases↗