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Biomedical subjects

T Fujioka

Publications and source records attributed to T Fujioka.

At least 19 recordsLinked to original sources
PubMed1997

The hupC gene product is a component of the electron transport system for hydrogen oxidation in Pseudomonas hydrogenovora.

The hydrogenase gene cluster containing nine genes (hupSLCDFGHIJ) was identified by sequencing of an 8.8-kb DNA region from Pseudomonas hydrogenovora. To investigate the function of the hupC gene product, we isolated a hupC-null mutant (HID3) of P. hydrogenovora by introducing an in-frame deletion into the hupC. The mutant, HID3, could not grow autotrophically but retained half the level of hydrogenase activity of the wild-type strain. Results of the oxygen consumption test and Western blot analysis revealed that the hupC gene product is a b-type cytochrome but not involved in the hydrogenase maturation process.

Amino Acid Sequence↗
PubMed1997

Effects of single administration of pravastatin sodium on hepatic cholesterol metabolism in rats.

Pravastatin sodium, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, was administered to rats at 500 mg/kg, and the changes in several parameters concerning the metabolism of cholesterol in the liver were determined over 12 h. HMG-CoA reductase activity began to be induced 6 h after pravastatin dosage and continued to increase for an additional 6 h. A significant reduction of serum and liver microsomal cholesterol was observed only at 9 h. At this time point, the protein mass and activity of cholesterol 7 alpha-hydroxylase were significantly decreased by 31% and 34%, respectively. Hepatic low density lipoprotein (LDL) receptor expression was not affected by pravastatin throughout the experimental period. These results suggest that, in rats, the compensatory mechanism to restore the cholesterol balance after depletion of liver cholesterol produced by a single administration of pravastatin might primarily depend on the induction of HMG-CoA reductase and might be facilitated by a reduction in cholesterol 7 alpha-hydroxylase, without the induction of hepatic LDL receptor.

Animals↗
PubMed1997

Helicobacter pylori infection accelerates human gastric mucosal cell proliferation.

Helicobacter pylori causes chronic atrophic gastritis and intestinal type gastric cancer arises against a background of atrophic gastritis. Increased proliferation of epithelial cells is an important indicator of increased risk for gastric adenocarcinoma. We investigated gastric mucosal cell proliferation in H. pylori-associated gastritis and the effect of eradication therapy on this proliferation in 45 patients endoscopically diagnosed (31 with persistent eradication and 14 in whom H. pylori) recurred. H. pylori status was determined by culture and histology in biopsied specimens from the gastric antrum and corpus. Eradication of the infection was defined as reversal to negative on both tests. In vitro Ki-67 immunostaining of endoscopic biopsy specimens was used to measure mucosal cell proliferation in H. pylori-associated gastritis before and after therapy. The proliferative zone was defined as the distance of Ki-67-positive gastric epithelial cells between the highest and the lowest cells. In patients in whom H. pylori was eradicated, cell proliferation in both the antral and corpus mucosa had decreased 4 weeks after completion of the eradication therapy (P < 0.01, P < 0.001), and 6 months later, it had markedly decreased (P < 0.05, P < 0.05) and returned to normal. In patients in whom H. pylori recurred, only antral epithelial cell proliferation was reduced 4 weeks after eradication therapy, but when H. pylori recurred, determined by culture and histology, cell proliferation level was the same as that before eradication. These results suggest that H. pylori infection accelerates cell proliferation in gastric mucosa and may play a causal role in the chain of events leading to gastric carcinoma.

Amoxicillin↗
PubMed1997

Characterization of sphingosine 1-phosphate-induced actions and its signaling pathways in rat hepatocytes.

Sphingosine 1-phosphate (S-1-P) and lysophosphatidic acid (LPA) stimulated glycogen phosphorylase, a rate-limiting enzyme responsible for glycogenolysis, in association with Ca2+ mobilization and phospholipase C (PLC) activation in rat hepatocytes. S-1-P, but not LPA, also inhibited adenosine 3',5'-cyclic monophosphate accumulation reflecting adenylyl cyclase inhibition. S-1-P-induced PLC activation, Ca2+ mobilization, and phosphorylase activation were markedly enhanced by primary culture of the cells for 24 h, whereas the inhibitory adenosine 3',5'-cyclic monophosphate response was unchanged by increasing culture time. Activation of the PLC-Ca2+ system during primary culture was specific to the lysosphingolipid; PLC and Ca2+ responses to LPA and NaF were unchanged or slightly attenuated by increasing culture time. Pertussis toxin treatment almost completely suppressed the S-1-P-induced inhibition of adenylyl cyclase but hardly influenced the lipid-induced activation of PLC and its cascade reactions. We conclude that S-1-P, through an LPA receptor-independent mechanism, stimulates two signaling pathways, i.e., activation of the PLC-Ca2+ system and inhibition of adenylyl cyclase, through distinct S-1-P receptor-transducer systems, resulting in the modulation of glycogenolysis in rat hepatocytes.

Animals↗
PubMed1997

Antitumor agents. 169 Dysoxylum cumingianum. V. Cumingianosides P and Q, new cytotoxic triterpene glucosides with an apotirucallane-type skeleton from Dysoxylum cumingianum.

Detailed chemical studies on the cytotoxic fraction from the leaves of Dysoxylum cumingianum have resulted in the isolation of two new triterpene glucosides, cumingianosides P (18) and Q (19), with an apotirucallane-type skeleton. The structures of 18 and 19 were determined by spectral examinations, and by conversion of cumingianosides C (3) and A (1) into 18 and 19, respectively. The cytotoxicities of cumingianosides P and Q against over 50 human cancer cell lines were evaluated. Cumingianoside P exhibited significant (EC50 < 4 microM) cytotoxicity against 37 human cancer cell lines. Among them, the UO-31 (renal cancer) cell line was the most sensitive to this compound (EC50 0.267 microM). In contrast, cumingianoside Q showed selective cytotoxicity against NCI-H522 (non-small cell lung cancer) cells with an EC50 value of 1.67 microM, and exhibited no cytotoxicity (EC50 > 10 microM) against most of the remaining cancer cell lines.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Antitumor agents. 168. Dysoxylum cumingianum. IV. The structures of cumingianosides G-O, new triterpene glucosides with a 14,18-cycloapotirucallane-type skeleton from Dysoxylum cumingianum, and their cytotoxicity against human cancer cell lines.

Nine new triterpene glucosides, named cumingianosides G-O (4-7, 9, 12-15), containing a 14,18-cycloapotirucallane-type skeleton were isolated from a cytotoxic fraction of the leaves of Dysoxylum cumingianum. The structures of the new compounds were established on the basis of chemical and spectral examinations. Evaluation of the cytotoxic activity of cumingianosides G-O showed that cumingianoside M exhibited significant (< 4 microM) cytotoxicity, especially against leukemia and melanoma cell lines.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Molecular typing of Helicobacter pylori: differences in pathogenicity among diverse strains.

Helicobacter pylori appears to be a species with strain diversity, according to studies carried out using various molecular biological techniques. Differences in pathogenicity caused by the strain diversity of H. pylori were therefore investigated. Two hundred and thirty strains were divided into four types by polymerase chain reaction-restriction fragment length polymorphism, and their relationship to endoscopic diagnosis, ammonia concentration of gastric juice, and urease activity were assessed. With regard to incidence by type, patients infected with type 1, type 2, and type 3 exhibited the highest incidences of gastric ulcer, duodenal ulcer, and gastritis, respectively. The urease activity of type 2 was significantly lower than that of types 1 and 3 (P < 0.05). These observations suggest differences in pathogenicity due to the strain diversity of H. pylori. However, the diversity of diseases related to H. pylori is also presumed to be caused by both the diversity of H. pylori strains and differences in the host immunological reaction. Future studies should be directed toward clarifying the entire pathogenic mechanism of H. pylori infection.

Bacterial Typing Techniques↗
PubMed1996

In vitro contraction of the canine corpus cavernosum penis by direct perfusion with prolactin or growth hormone.

PURPOSE: It is well established that hyperprolactinemia, most typically seen in prolactinoma patients, causes hypogonadism and impotence. There seems to be a good possibility that hyperprolactinemia causes impotence, at least partially via some intrinsic property of prolactin (PRL), rather than through its suppressive effects on the hypothalamic-pituitary-gonadal testosterone dynamics. In the present investigation, we used an in vitro canine model to attempt to clarify whether direct action of PRL on the corpus cavernosum penis may lead to erectile insufficiency. Growth hormone (GH) and placental lactogen (PL), both having close structural and functional homologies to PRL, were also studied. MATERIALS AND METHODS: Isometric tension measurement with cavernous strips was performed in the presence or absence of 10(-5) to 10(-9) M. PRL, GH, or PL in the perfusion medium. The tension change induced by the test substances was normalized relative to that induced by 120 mEq KCl. RESULTS: Both PRL and GH produced dose-related elevations (p < 0.01) of the cavernous tension, whereas PL and thiol-cleaved PRL in comparable doses were without effect (p > 0.05). When the tension rise produced by 120 mEq KCl was taken as 100%, the maximum contractions produced by PRL and GH were 80% and 110%. The minimum effective concentration was 10(-8) to 10(-7) M. for both PRL and GH. Pretreatment with indomethacin (10(-5) M.), but not tetrodotoxin (10(-5) M., partially suppressed (p < 0.05) the effects of PRL. CONCLUSION: These results suggest that PRL and GH directly and specifically produced contraction of the corpus cavernosum penis, resulting in erectile insufficiency, and that the effect of PRL is partially mediated by prostaglandin.

Animals↗
PubMed1996

Helicobacter pylori infection delays the healing of acetic acid-induced gastric ulcer in Japanese monkeys.

To clarify the relationship between Helicobacter pylori and the healing of gastric ulcers, we investigated the healing of acetic acid-induced gastric ulcers in the antral mucosa of Japanese monkeys (n = 5) infected with H. pylori and in control monkeys without H. pylori infection (n = 6). Using H. pylori-infected Japanese monkeys as an experimental model, gastric ulcers were induced endoscopically with acetic acid. Healing of ulcers and factors that influenced healing were studied. Continuous colonization with H. pylori was confirmed in the infected group throughout the observation period; no H. pylori were isolated from the gastric mucosa of the control group. White scarring was not observed in any infected monkeys 4 weeks after ulcer formation, but was observed in one (20%) of five monkeys at 6 weeks and in all five monkeys eight weeks after ulcer formation. In the control group, white scarring was observed in one (16.7%) of six monkeys at 4 weeks and in six monkeys at 6 (P < 0.01 vs infected group) and 8 weeks. The ammonia concentration of the gastric secretions and the grade of inflammation were significantly increased in the H. pylori-infected group compared with the control group (P < 0.01 and P < 0.001, respectively). The volume of intracellular PAS-positive substance was decreased (P < 0.025-0.01) at the ulcer margin in the infected group compared with the ulcer margin in the control group. The proliferation of gastric epithelial cells was markedly accelerated at the ulcer margin in the infected group compared with the ulcer margin in control group (P < 0.025-0.01). Our results strongly suggest that H. pylori infection delays the healing of gastric ulcers.

Acetic Acid↗
PubMed1996

Mechanisms of veno-occlusion within and outside the canine corpus cavernosum penis using a pressure-flow technique and cavernoso-venography.

BACKGROUND: Physiological erection of the penis requires multiple mechanisms causing an increase in the arterial blood influx into, and decrease in the venous drainage out of the cavernous space. METHODS: We investigated the extent and location of the venous occlusion that occurs with penile erection within (intrinsic mechanism) and outside (extrinsic mechanism) the corpus cavernosum penis, using 15 adult male mongrel dogs. Under controlled flows produced by a combination of aortic ligation and constant infusion of saline into the corpus cavernosum penis, or into the deep dorsal vein, pressures within the cavernous space or deep dorsal vein were measured before and after electrical stimulation of the pelvic splanchnic (pelvic nerve), the hypogastric, and pudendal nerve. An increase in pressure following nerve stimulations represented an increase in outflow resistance due to occlusion of the venous system. Pre-and post-stimulation radiologic evaluations were performed to determine the site(s) of venous occlusion. RESULTS: Unilateral stimulation of the pelvic nerve caused leftward shift of the corporeal pressure-flow curve. Bilateral stimulation of the pudendal nerve caused a marked rise in deep dorsal vein pressure. CONCLUSIONS: Both intrinsic and extrinsic venous occlusion mechanisms exist and that the former is activated primarily by unilateral stimulation of the pelvic nerve and the latter by bilateral stimulation of the pudendal nerve. The occlusion site for the extrinsic mechanism was localized to where the dorsal vein penetrates the muscles at the base of the pelvis, whereas the precise site for the intrinsic mechanism could not be determined.

Animals↗
PubMed1996

Testicular cancer in father and son.

The occurrence of testicular tumors in closely related family members is rare. We report a case of testicular cancers in a father and son. The father had pure seminoma, and his son developed a mixed nonseminomatous germ cell tumor. The peripheral blood lymphocytes in both patients were tested for 52 HLA specificities, and the patients were found to have six in common. The son was homozygous for HLA A24. The association between certain HLA antigens, other genetic factors, and testicular cancer requires further study to improve the care and counseling of patients and their families.

Adult↗
PubMed1996

Synthesis and biological activities of optically active 6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-quinolinone (OPC-18790).

The enantiomers of 6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-quinolinon e (OPC-18790), a novel cardiotonic agent, were synthesized and evaluated for positive inotropic activity. The key intermediates, 2,3-epoxypropoxy derivatives, were obtained by the alkylation of 6-hydroxy-2(1H)-quinolinone with optically active epichlorohydrin and subsequent ring closure. In an in vitro study, the (R)-(+)-isomer was about 10-fold more potent than the (S)-(-)-isomer.

Animals↗
PubMed1996

The mechanism of comparable serum cholesterol lowering effects of pravastatin sodium, a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor, between once- and twice-daily treatment regimens in beagle dogs and rabbits.

In dogs, no significant difference in the reduction of serum cholesterol was observed among three dosing regimens of pravastatin: once in the morning (3 mg/kg), once in the evening (3 mg/kg), and twice-daily (1.5 mg/kg x 2) for 21 days. In rabbits, pravastatin was administered at a dose of 50 mg/kg once-daily given in the evening or 25 mg/kg twice-daily for 14 days; the respective serum and liver cholesterol levels were decreased by 41% and 7% in the once-daily dosing and by 51% and 11% in the twice-daily dosing. The amount of low density lipoprotein (LDL) receptor protein was increased 1.2-1.3-fold (P < 0.05) by both treatments, and no significant difference was noted between these treatment regimens. In addition, there was no significant difference in the extent of up-regulated LDL receptor protein between once-daily dosing in the evening and once-daily dosing in the morning. In the experiments with rabbit hepatocytes, the up-regulated LDL receptor activity induced by preincubation with pravastatin was retained even 24 hr after the removal of pravastatin. These results suggest that the comparable efficacy of pravastatin between once- and twice-daily treatment could be explained by retention of up-regulated LDL receptor activity for more than 24 hr in vitro and in vivo.

Administration, Oral↗
PubMed1996

[Atherosclerosis regression in the elderly--correlation between centrally depressed lesions and risk factors].

Atherosclerotic plaque with central depression (depressed lesion) may indicate regression of atherosclerosis in the aorta. Aortic depressed lesions have a solitary elevated area of plaque with a sharply-bordered roung depression in its center and no area ulceration. This may be interpretable as a sign of regression of atherosclerosis. To clarify the pathogenesis of depressed lesion, we studied clinical risk factors such as hypercholesterolemia in patients with depressed lesions that were confirmed at autopsy. The patients were divided into 3 groups according to their total cholesterol level at autopsy: a high-risk group (> or = 220 mg/dl), a moderate-risk group (180-220 mg/dl), and a low-risk group (< or = 180 mg/dl). Depressed lesions were found in 16.4% of those in the high-risk group, in 14.6% of those in the moderate-risk group and in 69.0% of those in the low-risk group. Severe aortic atherosclerosis was found in 69.8% of the patients; 50.9% of those with severe disease were in the-low risk group. Depressed lesions were also found in those with low levels of low-density lipoprotein cholesterol (< or = 140 mg/dl), 58.8% of whom were found to have severe atherosclerosis. There was no relationship between total cholesterol level and the presence of depressed lesions. However, a clinical prevention trial may result in sufficient control of ahterosclerosis among those in the high-risk group and may also lead to regression of aortic lesions.

Aortic Diseases↗
PubMed1996

Epi-cochlioquinone A, a novel acyl-CoA : cholesterol acyltransferase inhibitor produced by Stachybotrys bisbyi.

A novel acyl-CoA : cholesterol acyltransferase (ACAT) inhibitor, designated epi-cochlioquinone A has been isolated from the fermentation broth of Stachybotrys bisbyi SANK 17777. The molecular formula, physicochemical properties, NMR spectroscopic analysis and X-ray crystallographic analysis revealed that this compound was a stereoisomer of cochlioquinone A, which has been previously reported as a nematocidal agent. It inhibited ACAT activity in an enzyme assay using rat liver microsomes with an IC50 value of 1.7 microM. However, it showed about 10-fold less potent inhibitory effect on plasma lecithin cholesterol acyltransferase (LCAT) than on ACAT. In addition, it inhibited in vivo cholesterol absorption in rats by 50% at 75 mg/kg.

Animals↗
PubMed1996

Schizostatin, a novel squalene synthase inhibitor produced by the mushroom, Schizophyllum commune. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.

In the process of screening for squalene synthase inhibitors from microbial fermentation products we have isolated a novel compound, named schizostatin (Fig. 1), from the culture broth of the mushroom, Schizophyllum commune SANK 17785. Schizostatin inhibited rat liver microsomal squalene synthase dose dependently and the IC50 value was 0.84 microM. The inhibition was competitive with respect to farnesylpyrophosphate with a Ki value of 0.45 microM.

Alkyl and Aryl Transferases↗
PubMed1996

Antitumor effects of angiogenesis inhibitor 0-(chloroacetyl-carbamoyl) fumagillol (TNP-470) against murine renal cell carcinoma.

PURPOSE: The effect of 0-(chloroacetyl-carbamoyl) fumagillol (TNP-470) on tumor growth and metastasis is investigated. MATERIALS AND METHODS: BALB/c mice were inoculated with Renca murine tumor and graded doses of TNP-470 were given subcutaneously every other day beginning on day 1 and ending on day 9. Tumor angiogenesis was measured quantitatively by a colorimetric assay. RESULTS: TNP-470 inhibited tumor growth and prolonged the life span of Renca-bearing mice in a dose-dependent manner. Body weight-loss was not observed in the mice given less than 30 mg./kg./day. When the treatment was delayed on day 6, TNP-470 did not inhibit tumor growth, pointing to the importance of the timing of drug administration in relation to disease stage. Tumor angiogenesis was inhibited 33 to 62% of the control level by TNP-470. Furthermore, TNP-470 reduced pulmonary and hepatic metastatic foci of intravenously inoculated Renca and of the tumor inoculated in the spleen. CONCLUSION: These data suggest that TNP-470 may be effective as a treatment of renal cell carcinoma, especially when micrometastases are involved.

Animals↗