Biomedical subjects
Publications and source records attributed to T Nohara.
Three pyridoxine derivatives have been isolated from the fresh stem bark of Albizzia julibrissin DURAZZ.. One of them, named julibrin II, was found to exhibit arrhythmic-inducing action. However, neither the others having the same aglycone nor some glycosides having the same sugar unit showed the action.
The effects of pH on the formation and dissociation of the complex of trypsin and PSTI was investigated using pancreatic juice of two patients. Pancreatic juice was eluted from a Sephadex G100 column with the buffer in different pH values, and the trypsin inhibitory activity in the eluate was measured. Under alkaline and neutral conditions, the complex of PSTI and trypsin was observed, while in acidic condition, dissociation of the complex was occurred. Molar ratio of PSTI and trypsin in the complex was found to be one mole/one mole. Human serum, alpha 1-antitrypsin, and alpha 2-macroglobulin dissociated the complex of PSTI and trypsin.
Secreting and producing capacities of alpha-fetoprotein (AFP) and albumin (ALB) by human hepatoma cell line (HH2-6) exposed to oxygen free radicals generated by dihydroxyfumarate (DHF) were studied in vitro. It was found that cell number were declined in proportion to DHF concentrations for 48 hrs culture and cell proliferations were inhibited by DHF in growth curve. The amount of AFP secreted per cell (secreting capacity) was decreased at high concentration of DHF (50 micrograms/ml) for 48 hrs culture, and remarkable elevation of AFP-secreting capacity for growth stage was inhibited even by DHF (10 micrograms/ml). On the other hand, ALB-secreting capacity was not affected with DHF. Producing capacities of AFP and ALB were correlated with secreting capacities. Cu, Zn-superoxide dismutase (Cu, Zn-SOD) interfered these reactions. These results suggest that oxygen free radicals inhibit cell proliferations and suppress AFP-secreting and producing capacities of HH2-6 cells selectively.
Methanolic extracts of the stalks of Mucuna birdwoodiana on acid hydrolysis and subsequent methylation with diazomethane provided four triterpene sapogenols. On the other hand, investigation of glycosides after methylation of the same extract led to the isolation of four triterpene glycosides. On the basis of chemical and spectral evidence, their structures were characterized as methyl asiatate, methyl maslinate, two new sapogenols, methyl 1 beta,2 alpha,3 beta,23-tetrahydroxyolean-12-en 28-oate (mucunagenin a), its urs-12-en isomer (mucunagenin b), 3-O-(6-O-methyl-beta-D-glucuronopyranosyl) methyl asiatate 3-O-[alpha-L-arabinopyranosyl(1----2)]-6-O-methyl-beta-D-glucur onopyranosyl methyl maslinate, 3-O-[alpha-L-arabinopyranosyl(1----2)]-6-O-methyl-beta-D-glucur onopyranosyl methyl asiatate and 3-O-(6-O-methyl-beta-D-glucuronopyranosyl) asiatic acid 28-O-beta-D-glucopyranoside.
The structures of two new steroidal glycosides named soladulcosides A and B, isolated from the aerial parts of Solanum dulcamara including new sapogenols, were elucidated as (22R, 25R)-3 beta, 15 alpha, 23 alpha-trihydroxy-5 alpha-spirostan-26-one 3-O-alpha-L-rhamnopyranosyl-(1----2)-beta-D-glucopyranoside and (22R, 25R)-3 beta,23 alpha-dihydroxy-5 alpha-spirostan-26-one 3-O-alpha-L-rhamnopyranosyl-(1----2)-[alpha-L-rhamnopyranosyl-(1----4)]- beta-D-glucopyranoside, respectively.
The present study was designed to examine the effects of methanolic extract (PE-ME), isoflavonoid fraction (PF-IF), triterpenoid saponin fraction (PF-SP) and N-acyl-N1-glucosyl-tryptophan (PF-P) isolated from puerariae flos on alcohol-induced unusual metabolism (as for glucose (BG), triglyceride (TG), and urea nitrogen (BUN) level in blood) and experimental liver injury (model: CCl4- and high fatty food induced) in mice. These alcohol-induced increasing responses were inhibited by the extracted and refined substances from puerariae flos. In short, PF-ME (4500 mg/kg) and PF-P (400 mg/kg) inhibited an increase in BG level induced by alcohol, whereas PF-IF (1000 mg/kg) and PF-SP (1000 mg/kg) did not. Similary, PF-ME and PF-SP inhibited an increase in TG induced by alcohol, whereas PF-IF did not. In addition, PF-IF and PF-SP inhibited increasing BUN level. Still more, PF-IF and PF-SP significantly inhibited an increase in gulutamate oxalacetate transaminase or gulutamate pyruvate transaminase level induced by high-fatty food and CCl4 in control animals. Especially PF-IF (250 mg/kg) administration showed a remarkable effect (inhibition: 76.3%) in control animals. These results suggested that puerariae flos or its combination drugs may be a useful drug as a traditional medicinal system for counteraction to drinking.
Plasma PGE2 level of 45 patients with digestive cancers, 10 patients with digestive benign diseases and 10 healthy controls were examined. Some patients were also examined plasma levels of TXB2, 6-keto-PGF1 alpha and PGF2 alpha. Plasma PGE2 level of digestive cancer patients (53.5 +/- 69.1 pg/ml, mean +/- SD) were about 10 times higher compared to healthy controls (5.2 +/- 3.8 pg/ml, p less than 0.01). Patients with digestive benign diseases also revealed elevated level of plasma PGE2, but the change of value were smaller than those of digestive cancer patients. Furthermore, in the case of digestive cancer patients, significantly elevated levels of TXB2 (49.7 +/- 60.3 pg/ml, p less than 0.05) and 6-keto-PGF1 alpha (33.9 +/- 31.5 pg/ml, p less than 0.01), and significantly reduced levels of PGF2 alpha (246 +/- 63 pg/ml, p less than 0.01) were noted. The changes in plasma prostaglandin levels of digestive cancer patients may reflect, even though prostaglandins are present in normal human body and are inactivated rapidly, the biological characteristics of tumors and in vivo reactions of the host.
A deceased 59-year-old woman with insulin dependent diabetes mellitus complicated by chronic thyroiditis and chronic hepatitis was autopsied. She had had diabetes mellitus since she was 30 years old, and insulin therapy was started at 34 years. Laboratory findings were as follows: s-GOT 85, s-GPT 31, gamma-globulin 2.45 g/dl. Immunological tests were positive for anti-smooth muscle antibody and anti-ENA antibody with high titers of antithyroglobulin and anti-microsome antibodies. HLA analysis revealed the presence of DR-4. The thyroid biopsy specimen showed microscopic features characteristic of chronic thyroiditis at 52 years of age. She had been repeatedly admitted for the control of diabetes mellitus. She was admitted for the 9th time in June, 1987 following complaints of abdominal pain. After admission, her general condition became gradually worse, and she died of peritonitis in September, 1987. Pathological examination of the liver revealed an expansion of fibrous tissue on Glisson's capsule accompanied by lymphocytic infiltration and was diagnosed to be chronic inactive hepatitis. As for the thyroid gland, fibrous tissue replaced an extensive area of the thyroid gland, and normal thyroid tissue was not observed. Lymphocytic infiltration was less in comparison with that in the previous biopsy. As for the pancreas, atrophy of exocrine pancreatic tissue and fibrous change in interstitial tissue was observed. Lymphocytic infiltration was also seen in the interstitial exocrine tissue but not in the islet. Immunohistochemical examination of the islets using anti-insulin, glucagon and somatostatin antibodies by ABC peroxidase method showed the selective disappearance of B cells in the islets. The pathological changes in the thyroid gland, liver and pancreas suggest that autoimmune mechanism may be involved in the pathogenesis of chronic thyroiditis, chronic hepatitis and IDDM with exocrine pancreatic impairment in this case.
The proton and carbon-13 nuclear magnetic resonance signals of cytochalasin E (1) were assigned with the aid of 1H-1H, 1H-13C and 1H-13C long-range chemical shift correlation spectroscopy spectra, and the structure of the decomposition product (2) generated under neutral conditions was determined.
Two triterpenoid saponins (1 and 2) were isolated from Desmodii Herba [the dried whole plants of Desmodium styracifolium (Osbeck) Merr. (Leguminosae)] and their chemical structures were characterized as soyasaponin I and a new saponin, 3-O-[alpha-L-rhamnopyranosyl-(1----2)-beta-D-galactopyranosyl- (1----2)-beta-D-glucuronopyranosyl]soyasapogenol E, respectively, by chemical and spectroscopic means.
The 70% acetone extract of Monochasma savatierii FRANCH. et MAXIM. showed very strong inhibition of rabbit lens aldose reductase (AR). From the active fraction, five iridoid glucosides along with the two phenolic glycosides, acteoside and dehydroacteoside, have been isolated. Among them, acteoside showed the highest activity, being about 2.5 times more potent than baicalein, a known natural inhibitor of AR (IC50 = 9.8 x 10(-7) M). Demethylmussaenoside and 7-O-acetyl-8-epi-loganic acid, which are iridoid glucosides, had weak inhibitory activity.
In the general rule, Puerariae Flos or it's combination drugs are used in traditional medicinal system for counteraction to drinking among Japanese and Chinese therapy. One of such drugs is Kakkakaiseito. Here we report the results of investigation on some pharmacological actions including alcoholic metabolism. The experiments were carried out to confirm its actual effect on alcohol, acetaldehyde and ketone body metabolism in the blood and the alteration of behaviour pattern of mice. Drugs used in this study were methanolic extract (PF-ME), isoflavonoid fraction (PF-IF) and triterpenoid saponin fraction (PF-SP) isolated from Puerariae Flos. Each drug was orally administrated to mice. These results were shown as follows: the concentrations of blood alcohol and acetaldehyde decreased more after the treatment with PF-IF (800 mg/kg) than those of the control group. This fact was evidenced remarkable effects with area under the blood concentration-time curve, mean residence time, and variance residence time and values on the moment analysis. However, a reduction effect was not recognized by the treatment with PF-SP (1000 mg/kg). Moreover, PF-ME and PF-IF suppressed the increment of spontaneous movement induced by alcohol administration, whereas PF-SP did not prevent the decrease in the increment caused by alcohol administration. These results support the basis that Puerariae Flos or its combination drugs is used in a traditional medicinal system for counteraction to drinking. However, further investigation is necessary.
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M-GTFI, an inhibitor of glucosyltransferase from S. mutans was produced by Micromonospora narashinoensis strain No. 731. The isolation procedure for M-GTFI was improved and established for spectroscopic analyses, and some properties of the inhibitor were investigated. The structure of M-GTFI was shown to be trisodium [2-sulphonato-(E)-9-undecenyll-oxacyclotriacont-(E)-3- en-2-one, 16, 18-bis sulphonate. The chemical structure of M-GTFI was therefore similar to that of izumenolide which is a beta-lactamase inhibitor containing sulfate ester groups in its molecule. The inhibitory characteristics of M-GTFI were parallel to that of other inhibitory compounds containing sulphate esters but the spectrum of activity was wider.
In order to investigate the production of PGE2 and its' function in human hepatocellular carcinoma, the effects of indomethacin and PGE2 on tumor growth were examined using in vivo and in vitro techniques. HH2-6 cells produced PGE2 in the culture media, and the inverse relationship was observed in between the cell proliferation and the culture supernatant PGE2 levels. While in vivo, plasma and tumor tissue PGE2 levels of tumor bearing nude mice were significantly increased for 1 or 2 weeks after tumor inoculation. In the case of which indomethacin was injected daily into the abdominal cavity (4 mg/kg body weight), the elevation of plasma and tissue PGE2 levels was remarkably suppressed, and the latent time of tumor growth was also prolonged. On the other hand, another case of which PGE2 was injected (10 micrograms or 0.1 microgram i.p.) at first 10 days revealed shortened latent time. These results indicate the intimate relation between PGE2 and latent time on tumor growth. Furthermore, histological findings suggest that tumor derived PGE2 might play an important role in tumor angiogenesis.
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In this study, we investigated protein (total protein) synthesis and production of such as alpha-fetoprotein (AFP) and albumin (ALB) in the media for cultured human hepatocellular carcinoma cells. Consequently, it was found that total protein (TP) in the medium was consumed rapidly in the first day, thereafter TP consumption was not quantitatively significant. Since this cell line was also found to produce transferrin (TF) and fibronectin (FN), we investigated the AFP, ALB and TF production of this cell line by adding dexamethasone, a glucocorticoid involved in protein metabolism. As a result of adding dexamethasone, it was found that AFP and ALB (or TF) production increased simultaneously.
We experienced two primary lung cancer patients who showed high levels of CA19-9 (Carbohydrate Antigen 19-9). One case was small cell carcinoma and the other was adenocarcinoma. In contrast to malignancies of digestive organ origin, rare CA19-9 positive cases are reported in lung cancer. To get evidences that these lung cancer tissues were producing CA19-9, PAP stain (Peroxidase anti peroxidase method: Sternberger) was performed, and positive stains were obtained in tumors surgically removed from these two patients. Especially in a patient who showed very high level of CA19-9 (27,369 U/ml), almost every tumor cell was positively stained. From these findings, we suggest the importance of checking CA19-9 in patients with lung cancer.