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Biomedical subjects

S Fujii

Publications and source records attributed to S Fujii.

At least 793 records · Page 44Linked to original sources

Left ventricular function in patients with diabetes mellitus.

The left ventricular function was assessed in 70 diabetics under 60 years of age without clinically evident heart disease using established non-invasive methods, these include systolic time interval method and echocardiography. The ratio of pre-ejection period to left ventricular ejection time (PEP/ET) was remarkably elevated in diabetics with severe microangiopathy (0.431 +/- 0.037). Even in diabetics without microangiopathy PEP/ET ratio was significantly higher (0.374 +/- 0.037) compared with that in controls (0.331 +/- 0.023, P less than 0.01). Most of diabetics with a PEP/ET value of higher than 0.40 were not under proper care with regard to diabetic control. A tendency toward normalization of PEP/ET values was often observed with the improvement in diabetic control during six to twelve months among the inadequately controlled diabetics. Isovolumic relaxation time in diabetics was longer than in controls (80 +/- 14 msec, 59 +/- 11 msec, P less than 0.005). Our results suggest that abnormalities of left ventricular function in diabetics may be related to not only severity of microangiopathy but also the state of diabetic control. The maintenance of adequate control of diabetes seems to play an important role in the prevention of congestive heart failure in patients with diabetes mellitus.

Adolescent↗

Molecular epidemiology of adenovirus type 8 (Ad 8) in Taiwan: four subtypes recovered during the period of 1980-1981 from patients with epidemic keratoconjunctivitis.

Adenovirus type 8 (Ad 8) has been the major and important causative agent of epidemic keratoconjunctivitis (EKC). By enzymatic cleavage analysis with five endonucleases, PstI, HindIII, BamHI, SalI and SstI, 27 out of 149 Ad 8 isolates recovered from patients with EKC during the period from July, 1980 to July, 1981 in Kaohsiung, Taiwan, were studied. By cleavage patterns, 27 Ad 8 isolates in Kaohsiung were classified into four subtypes which were found to be different from the subtypes (Ad 8A, Ad 8B) prevalent in Sapporo (1).

Adenoviruses, Human↗

[Development of fluoropyrimidine derivatives].

5-Fluorouracil (5-FU), first synthesized by Heidelberger et al. in 1957 has been used extensively in the treatment of cancer. In the process of development antitumor drugs in fluoropyrimidine, 5-FU and 5-fluorodeoxyuridine (FdUrd) were chosen because these two drugs relatively were incorporated into tumor tissues more than into normal tissues. The toxicity of 5-FU seems to be proportional to its concentration in blood. To be effective clinically, the concentration of a therapeutic drugs (5-FU and FdUrd) should be high in the tumor and low in the blood. In this paper, the characterization of masked forms of 5-FU and FdUrd were described as follows: Metabolism of 5-FU and uracil. Conversion of FT-207 to 5-FU (P-450). Prove in chemotherapy of cancer by oral administration of FT-207. Theory of co-administration of FT-207 with uracil (UFT-therapy). Conversion of 5'DFUR (5'deoxy-5-fluorouridine) to 5-FU (Pyrimidine nucleoside phosphorylase). Conversion of FF-705a 2'-deoxy-3', 5'-O- diacetyl-5-fluoro-3-(3-methylbenzoyl)-uridine to FdUrd and 5-FU, and fluctuation of 5-FU and FdUrd levels in the blood after oral administration of FF-705a.

Animals↗

[A light and electron microscopic studies of müllerian adenofibroma of the uterus].

Müllerian adenofibroma composed of both histologically benign epithilia and benign mesenchyme is considered to be a rare entity of mixed müllerian tumor. A case of müllerian adenofibroma of the uterus was studied by light and electron microscopy. Light microscopically, the cleft-like glands lined by single-layered columnar or cuboidal epithelial cells were distributed in the proliferation of surrounding fibroblast-like mesenchymal cells. Mitotic figures of mesenchymal cells were less than 1--2 in 10 high power fields, and no nuclear atypia or heterologous elements were observed. Electron microscopically, the epithelial cells had well-developed mitochondria, r-ERs, tonofilaments in the cytoplasm, and short microbilli or cilia protruding into the lumen. In the mesenchyme, two types of cells were observed. One was spindle-shaped cells resembling fibroblasts, and the other was cells resembling immature smooth muscle cells. The histological and ultrastructural features of müllerian adenofibroma were felt to resemble those of müllerian adenosarcoma, which may pursue a clinically malignant course. These findings suggest that müllerian adenofibroma and adenosarcoma may be in the common spectrum of mixed müllerian tumor.

Adenofibroma↗

[Role of hysteroscopy in diagnosis and management of trophoblastic disease].

To confirm complete removal of trophoblastic tissues, hysteroscopy was performed in 21 patients after evacuation of hydatidiform mole with an interval of a week. In 15 of these cases, hysteroscopy employed within a week after evacuation of the mole revealed a residue of mole or necrotic decidua. Although complete removal was confirmed in 14 cases on the second hysteroscopy, re-curettage was necessary in 6 patients because necrotic tissues were still found in the uterine cavity. Possible diagnosis of invasive mole was made in 2 cases within 2 weeks after evacuation of the mole by hysteroscopic findings. Hysteroscopy was also performed in 27 patients who were suspected of having a trophoblastic disease from the clinical signs and urinary hCG titer. Hysteroscopic findings which suggested trophoblastic diseases were summarized in the following four categories; 1) the existence of vesicles, 2) buldging or 3) recess of the uterine wall with bleeding or dilated blood vessels and 4) hematoma of the uterine wall. In 9 of the 21 cases with choriocarcinoma, invasive mole or persistent trophoblastic disease, one or two of the above mentioned findings were noted. Moreover, it was possible to differentiate syncytial endometritis from trophoblastic disease from the hysteroscopic findings. Therefore, hysteroscopy seems to be a useful aid not only in confirming complete evacuation of hydatidiform mole but also in the diagnosis and management of malignant sequela.

Chorionic Gonadotropin↗

[Regulation of enzyme activities involved in pyrimidine synthesis and its application to cancer chemotherapy].

We examined the enhancing effect of antitumor activity by co-administration of 5-FU or its masked form (FT-207) with bases or nucleosides of purine and pyrimidine. It was found that the antitumor activity of 5-FU or FT-207 on sarcoma-180 and AH-130 tumor was oral administration of uracil, deoxyuridine, uridine, thymine or thymidine. Uracil had more effect than other pyrimidine nucleotides in enhancing antitumor effect of these drug to FT-207 without toxicity. In contrast to the results with FT-207, co-administration of uracil with 5-FU increased its antitumor activity and also the toxicity of 5-FU. On the ther hand, no enhancing antitumor activity of dRib-1-P, Rib-1-P, Ado, Xao, Guo, Ino, dAdo, dIno and dGuo to FT-207 was observed. Concentration of 5-FU in the tumor, blood and various organs of AH-130-bearing rats after oral administration of clinical doses of FT-270 and uracil was examined. On oral administration of FT-207 plus uracil in various combinations, the highest T/B (ratio of concentration of 5-FU in the tumor to that in blood) value was obtained at a ratio of uracil to FT-207 of 4. Moreover, it was found that 5-FU was mainly phosphorylated in the tumor tissues whereas it was mainly degraded in liver slices. Degradation of 5-FU in vitro was inhibited more by thymine than by uracil. Phosphorylation of 5-FU, however, was not inhibited by uracil, thymine or thymidine, even times the concentration of 5-FU. These findings suggest that the enhancement of antitumor activity of 5-FU-masked form is more important the inhibition of 5-FU degradation than the stimulation of 5-FU phosphorylation.

Administration, Oral↗

[Studies on the mechanism of antitumor activity of 5-FU and its derivatives--relationship between the inhibition of tumor growth and the inhibition of thymidylate synthetase in vivo].

The relationship between the antitumor activity and the inhibition of thymidylate synthase after oral administration of 5-FU, FT-207 or UFT was examined. The inhibition of tumor growth on sarcoma-180 after oral administration of 5-FU (20 mg/kg), FT-207 (120 mg/kg) or UFT (30 mg/kg) was 40%, 50% or 70%, respectively. It was found that the inhibition of thymidylate synthase in sarcoma-180 tumor tissue after single oral administration of 5-FU (20 mg/kg), FT-207 (30 or 120 mg/kg) or UFT (30 mg/kg) were about 45%, 20%, 50% or 65%, respectively, but the activities of other enzymes involved in DNA synthesis were not almost inhibited. Thymidylate synthase was inhibited more severely by oral administration of UFT (30 mg/kg). The activities of other enzymes were not inhibited even by continuous oral administration of these drugs for 6 or 11 days. The extent of inhibition of thymidylate synthase seemed to be parallel to that of inhibition of tumor growth. These results suggest that the inhibition of thymidylate synthase by FdUMP converted from 5-FU, FT-207 or UFT plays a major role in their antitumor actions.

Animals↗

Development of smooth muscle in the human fetal uterus: an ultrastructural study.

Prenatal development of uterine smooth muscle was studied by light and electron microscopy in specimens obtained from ten human fetuses between 12 and 40 weeks gestation. Light microscopical observation of transverse sections of the body of the uterus revealed that the outer, subserosal layer of elongated cells was distinguishable from 14 weeks. This layer was more cellular than the inner layer and increased its thickness with advancing age. Ultrastructurally, the mesenchymal cells of the uterus did not contain myofilaments until 16 weeks. At 18 weeks, however, spindle shaped cells in the outer layer had a few filaments with dense bodies and well developed organelles and were identified as immature smooth muscle cells. By 31 weeks, the cells in this layer developed into almost mature smooth muscle cells, which contained abundant cytoplasmic filaments, dense plaques and surface vesicles along the cell membrane, and an external lamina. Therefore, in the human fetal uterus, smooth muscle differentiation begins at about 18 weeks and myometrium is formed in the outer layer of the wall by 31 weeks gestation. In the inner layer of the uterus that corresponds to the endometrial stroma, in addition to fibroblast-like cells, there were cells with plump cytoplasm which contained well developed granular endoplasmic reticulum and Golgi apparatus and which were identified around blood vessels by 26 weeks. These features resembled those of predecidual cells, and suggested the influence of sex steroids on the human fetal uterus.

Cell Differentiation↗

Characterization of the activity of growth factor from AH-130 tumor cells.

The activation of DNA synthesis induced by growth factor from the cytosol of AH-130 tumor cells (AH-130GF) was inhibited by alkylamines (methylamine, ethylamine, and dansylcadaverine), which inhibit the intracellular processing of hormone-receptor complexes. Calmodulin inhibitors (trifluoperazine and W-7) also inhibited the mitogenic action of AH-130GF, suggesting that the Ca-calmodulin system and proteolytic processing in lysosomes are necessary for stimulation of DNA synthesis by AH-130GF after its binding to the cell surface. Membrane phosphorylation induced by AH-130GF or epidermal growth factor (EGF) was investigated by using rat liver plasma membranes and 3T3 cell membranes in vitro. EGF increased the phosphorylation of two protein components with molecular weights of 160K and 130K in rat plasma membranes, but AH-130GF increased the phosphorylation of only the 130K protein. No specific phosphorylation induced by AH-130GF was detected in 3T3 cell membranes, but EGF induced phosphorylation of the 160K receptor protein.

Animals↗

[Histogenetic considerations of experimentally induced adenomatoid tumor-like nodules produced by sex steroids].

Glandlike structures with intervening fibrous stroma were observed in about 20% of subperitoneal nodules produced in the abdominal cavities of guinea pigs treated with various doses of estradiol benzoate (E) for 3 months. These glandlike structures were composed of cells resembling mesothelium, ciliated cells, cells with mucin in the cytoplasm and cells with a squamous appearance. Glandlike structures similar to those following estrogen treatment alone were also observed in about 20% of the nodules produced in the guinea pigs by pre-treatment with E and followed by combination treatment with E and progesterone (P) for 1 to 3 months. However, the glandlike structures were composed only of cells resembling mesothelium and cells with cilia. Both of these glandlike structures resembled adenomatoid tumors. We therefore conjecture that the formation of gland-like structures in the subperitoneal nodules is the result of mesothelial inclusions and their proliferation, and that some of these mesothelial cells were differentiated into ciliated, mucinous and squamous cells by estrogen.

Abdominal Neoplasms↗

Glutathione-dependent protection against oxidative damage of the human red cell membrane.

Glutathione (GSH) dependent protection against oxidative damage of human red cell membrane was examined. An artificial system was used in which chloroform/methanol-extracted red cell lipids, in the form of liposomes, were subjected to attack by a peroxidation system consisting of ascorbate-Fe3+. Human erythrocytes contained a nondialyzable factor, completely inactivated by heating in a boiling water bath for 3 min, which showed GSH-dependent inhibition against lipid peroxidation and was devoid of GSH peroxidase activity. On the other hand, GSH-S transferase, highly purified by affinity chromatography, had no inhibitory activity. These findings strongly indicate that the GSH-dependent protection against lipid peroxidation of human red cell membrane is mediated by one or more proteins other than GSH peroxidase and GSH-S transferase.

Erythrocyte Membrane↗

19-Hydroxylation of 18-hydroxy-11-deoxycorticosterone catalyzed by cytochrome P-45011 beta of bovine adrenocortex.

When 18-hydroxy-11-deoxycorticosterone was incubated with adrenocortical mitochondria fortified by adding exogenously adrenodoxin reductase and adrenodoxin in the presence of an NADPH-generating system, the steroid was converted to two products which were separated by high performance liquid chromatography. The retention time of one product was identical with that of 18-hydroxycorticosterone, an expected product of 11 beta-hydroxylation, whereas the retention time of the other was not coincident with those of any other corticosteroids examined. Production of the unidentified substance was also shown when 18-hydroxy-11-deoxycorticosterone was incubated with purified cytochrome P-45011 beta and its electron transport system. The ratio of the two products was always constant, even when various incubation conditions were employed with regard to reaction time, the substrate concentration, and the cytochrome concentration. Structural determination of the unidentified product was conducted by mass spectrometry and 1H NMR spectrometry. The results of these analyses indicated that the substance was 18,19-dihydroxy-11-deoxycorticosterone, a hitherto unreported corticosteroid.

18-Hydroxydesoxycorticosterone↗

Effects of histamine on mechanical performance and biochemical and electrical activity in the heart of monkeys (Macaca fuscata).

The properties of the cardiac effects of histamine on the isolated heart muscles of the Japanese monkey (Macaca fuscata) were investigated. Histamine had a concentration-dependent positive inotropic effect on left atria and papillary muscles and a positive chronotropic effect on right atria. Histamine increased the levels of cyclic AMP and shortened the duration of the action potential in Purkinje fibers, measures of its biochemical and electrophysiological effects. All of these effects of histamine were blocked by 10(-5) M cimetidine. These results indicate that histamine H2-receptors mediate the cardiac effects of histamine on the monkey heart. Histamine (10(-5) M) also restored the action potentials and contractility of K+-depolarized preparations. These effects were inhibited by verapamil (10(-6)-10(-5) M) but not by TTX (10(-5) M), suggesting that, in the monkey heart, histamine may act by increasing the slow inward current.

Action Potentials↗