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Biomedical subjects

Y Yano

Publications and source records attributed to Y Yano.

At least 73 records · Page 4Linked to original sources

Novel prenyltransferase gene encoding farnesylgeranyl diphosphate synthase from a hyperthermophilic archaeon, Aeropyrum pernix. Molecularevolution with alteration in product specificity.

Prenyltransferases catalyse sequential condensations of isopentenyl diphosphate with allylic diphosphates. Previously, we reported the presence of farnesylgeranyl diphosphate (FGPP) synthase activity synthesizing C25 isoprenyl diphosphate in Natronobacterium pharaonis which is a haloalkaliphilic archaeon having C20-C25 diether lipids in addition to C20-C20 diether lipids commonly occurring in archaea [Tachibana, A. (1994) FEBS Lett. 341, 291-294]. Recently, it was found that a newly isolated aerobic hyperthermophilic archaeon, Aeropyrum pernix, had only C25-C25 diether lipids, not the usual C20-containing lipids [Morii, H., Yagi, H., Akutsu, H., Nomura, N., Sako, Y. & Koga, Y. (1999) Biochim. Biophys. Acta 1436, 426-436]. In this report, we describe the isoloation from A. pernix of the novel prenyltransferase gene, fgs, encoding FGPP synthase. The protein encoded by fgs was expressed in Escherichia coli as a glutathione S-transferase fusion protein and produced FGPP as a final product. Phylogenetic analysis of fgs with other prenyltransferases revealed that the short-chain prenyltransferase family is divided into three subfamilies: bacterial subfamily I, eukaryotic subfamily II, and archaeal subfamily III. fgs is clearly contained within the archaeal geranylgeranyl diphosphate (GGPP) synthase group (subfamily III), suggesting that FGPP synthase evolved from an archaeal GGPP synthase with an alteration in product specificity.

Alkyl and Aryl Transferases↗

Troglitazone reduces plasma levels of tumour necrosis factor-alpha in obese patients with type 2 diabetes.

We evaluated the effect of troglitazone (given orally 400 mg/day) on glucose intolerance and on the plasma levels of tumour necrosis factor-alpha (TNF-alpha) in 12 obese patients with type 2 diabetes for 12 weeks. Troglitazone significantly decreased fasting plasma glucose, serum C-peptide, serum insulin and HbA1c levels. Plasma levels of TNF-alpha were significantly reduced by troglitazone administered for 8 and 12 weeks. Troglitazone administration significantly improved insulin resistance, but did not affect pancreatic beta-cell function as evaluated by the homeostasis model assessment (HOMA). In the present study, we reported for the first time that troglitazone administration significantly reduces plasma levels of TNF-alpha in obese patients with type 2 diabetes.

Blood Glucose↗

Vitamin E inhibits cell proliferation and the activation of extracellular signal-regulated kinase during the promotion phase of lung tumorigenesis irrespective of antioxidative effect.

We have already reported that the activation of extracellular signal-regulated kinase (Erk) is critical in the stimulation of cell proliferation during the promotion stage of urethane-induced lung tumorigenesis in mice. Also, we have found that vitamin E suppresses lung tumorigenesis by inhibiting cell proliferation at the promotion stage. However, it is still unclear whether this inhibitory effect at the promotion stage is based on the antioxidative effect of vitamin E or not. In order to address this question, we examined the inhibitory effect of alpha-tocopheryloxybutyric acid (TSE), an ether derivative of vitamin E that cannot act as an antioxidant in vivo, on cell proliferation and the activation of Erk during promotion of lung tumorigenesis. On day 30 after urethane injection (750 mg/kg, i. p.) in A/J mice, TSE or vitamin E at 100 micromol/kg, p.o. was administered. Twenty-four hours after the final administration, the mice were killed to analyze cell proliferation and related parameters. The labeling index of proliferating cell nuclear antigen (a marker of cell proliferation) and ornithine decarboxylase activity (a marker of the promotion stage in lungs) were attenuated by treatment with TSE or vitamin E. TSE or vitamin E treatment also inhibited urethane-induced activation of Erk and suppressed the activation of other essential members of the Erk cascade (Ras, Raf and Mek). These results suggest that vitamin E inhibits cell proliferation and activation of the Erk cascade during promotion of urethane-induced lung tumorigenesis in mice, independent of its antioxidative effect.

Animals↗

Chemopreventive effect of 24R,25-dihydroxyvitamin D(3) in N, N'-dimethylhydrazine-induced rat colon carcinogenesis.

In this study we investigated the effects of 24R,25-dihydroxyvitamin D(3) [24R,25(OH)(2)D(3)] on N,N'-dimethylhydrazine (DMH)-induced rat colon carcinogenesis. For experiments 1 and 2, 50 F344 male, 6-week-old rats were divided into five groups in each experiment. Animals were given s.c. injections of DMH once a week for 4 weeks. Those in groups 1-5 were given 24R,25(OH)(2)D(3) in the diet (10, 5, 2.5, 1.25 or 0 p.p.m., respectively) during the post-initiation stage in experiment 1 and during the initiation stage in experiment 2. At termination, the numbers of aberrant crypt foci (ACF) in the rat colonic mucosa were decreased dose-dependently in rats treated with 24R,25(OH)(2)D(3) during the post-initiation stage, but not in the initiation stage. For experiment 3, 15 male, 9-week-old rats were divided into three groups and given 24R,25(OH)(2)D(3) in the diet (10, 5 or 0 p.p.m.). Animals were injected with 5-bromo-2'-deoxyuridine (BrdU) i.p. 1 h before death to examine DNA synthesis in the colon mucosa. BrdU labeling indices were decreased dose-dependently in colonic crypts of rats treated with 24R, 25(OH)(2)D(3). In experiment 4, using the multicarcinogenic protocol we could analyze our data with respect to not only one separate organ, but at the organism level. Sixty-eight male, 6-week-old rats were treated with DMH, N-methylnitrosourea, 2, 2'-dihydroxy-di-n-propylnitrosamine, diethylnitrosamine and N-butyl-N-(4-hydroxybutyl)nitrosamine in weeks 1-4 and were then given 24R,25(OH)(2)D(3) in the diet (5, 1 or 0 p.p.m.) throughout weeks 5-30. Examination of the development of tumors and preneoplastic lesions in various organs revealed that 24R, 25(OH)(2)D(3) inhibited colonic tumor development significantly but exerted no effects on tumor induction in other organs. In conclusion, these results strongly indicate that 24R,25(OH)(2)D(3) inhibits colon carcinogenesis specifically, without any enhancement of carcinogenesis in other organs, when administered in the post-initiation phase.

1,2-Dimethylhydrazine↗

Inhibitory effects of 1,3-diaminopropane, an ornithine decarboxylase inhibitor, on rat two-stage urinary bladder carcinogenesis initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine.

Overexpression of ornithine decarboxylase (ODC) has been shown to be characteristic of tumor development and progression in humans and experimental animals. Therefore, we have examined the effects of 1, 3-diaminopropane dihydrochloride (DAP), a potent inhibitor of ODC, on rat two-stage urinary bladder carcinogenesis initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). In experiment 1 (36 weeks), 6-week-old F344 male rats were administered 0.05% BBN in drinking water for 4 weeks and then divided into four groups. Animals of groups 1 and 2 received basal diet and drinking water supplemented with or without DAP (2 g/l). Groups 3 and 4 were given diet containing 5% sodium L-ascorbate (NaAsA), a typical urinary bladder tumor promoter, and drinking water with or without DAP. Administration of DAP to group 1 significantly reduced tumor size, multiplicity and incidence, particularly of papillomas, when compared with group 2 values. DAP together with NaAsA (group 3) also decreased tumor size relative to the group 4 case. To determine the effects of DAP on the early stages of bladder carcinogenesis and its mechanisms, a similar protocol was conducted (experiment 2) with death after 20 weeks. DAP treatment caused complete inhibition (0% incidence) of papillary and/or nodular hyperplasia in group 1 but was without influence in group 3, as compared with the respective controls. Moreover, the ODC activity, bromodeoxyuridine labeling indices and mRNA expression levels of cyclin D1 in the urinary bladder mucosa, determined by northern blotting, were markedly lower in group 1 than in group 2, but values were comparable for both groups administered NaAsA. Assessment of mRNA expression levels of the angiogenic vascular endothelial growth factor suggested no involvement in the inhibitory effects of DAP on urinary bladder carcinogenesis. The results indicate that inhibition of ODC could reduce urinary bladder carcinogenesis in rats, particularly in the early stages, through antiproliferative mechanisms.

Acetyltransferases↗

Chemotherapy for hepatocellular carcinoma with portal hypertension due to tumor thrombus.

A case of hepatocellular carcinoma (HCC) complicated by tumor thrombosis of the main trunk is presented. Four courses of hepatic arterial infusion therapy, via a subcutaneously implanted injection port, were performed using cisplatin (10 mg for 1 hour on days 1-5) and 5-fluorouracil (250 mg for 5 hours on days 1-5). After four courses of the chemotherapy, marked reduction in size of HCC and the tumor markers were noted. The esophageal varices and ascites were improved after the chemotherapy with a recanalization of the left branch of the portal vein. The patient was doing well with a survival period of 28 months after the chemotherapy. These encouraging results suggested that the present therapy, based on the biochemical modulation, was a useful option for advanced HCC with portal hypertension due to tumor thrombosis of the main portal vein.

Aged↗

Characterization and identification of Borrelia isolates as Borrelia valaisiana in Taiwan and Kinmen Islands.

Eleven pure cultures of Borrelia from 3 species of wild rodents (Apodemus agrarius, Mus formosanus, Rattus losea) captured in Taichung, located in the center of Taiwan island, and on Kinmen Island were characterized. Five isolates showed restriction fragment length polymorphism (RFLP) patterns of 5S-23S rRNA gene intergenic spacer sequences identical to those of strains 5MT and 10MT, identified as Borrelia valaisiana, which were isolated in the southern tip of South Korea. Although the remaining six isolates showed novel RFLP patterns, these isolates showed more similarity to members of B. valaisiana from Korea, Japan and Europe based on 16S rRNA gene and flagellin gene sequences. This led us to speculate that transmission and proliferation of this type of borrelia occurred between Taiwan and the southern part of South Korea.

Animals↗

Chemopreventive effects of bovine lactoferrin on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced rat bladder carcinogenesis.

Chemopreventive effects of bovine lactoferrin (bLF), which is found at high concentrations in colostrum, on rat bladder carcinogenesis were investigated using a rat bladder medium-term bioassay. In experiment 1, a total of 80 F344 male rats, 6 weeks old, were divided into 5 groups. Groups 1 and 2 were treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in the drinking water for 8 weeks and after a 1-week interval, received dietary supplementation with 2% and 0.2% bLF, respectively. Group 3 received 0.05% BBN for 8 weeks and then no treatment. Group 4 was administered 2% bLF alone from week 9, without prior carcinogen exposure. Group 5 was maintained without any treatment throughout the experiment. All rats were killed at the end of week 36. Group 1 demonstrated a significantly decreased multiplicity of the bladder tumors (carcinomas and papillomas) as compared with group 3. Maximum cut surface areas of bladder tumors were also significantly decreased in groups 1 and 2 compared with group 3. No bladder tumors were observed in groups 4 or 5. In experiment 2, a total of 60 rats were divided into two groups (30 rats each); both were treated with 0.05% BBN for 4 weeks and after a 1-week interval, one received 2% bLF (group 1) and the other, basal diet (group 2) for 4 weeks. Group 1 demonstrated a tendency for decrease of the 5-bromo-2'-deoxyuridine (BrdU) labeling index. bLF was detected in the urine of rats fed bLF by ELISA as well as western blot analysis. The findings indicate that 2% bLF can inhibit BBN-induced rat bladder carcinogenesis, and that this may be due to bLF in the urine.

Acetyltransferases↗

Inhibitory effects of S-methylcysteine and cysteine on the promoting potential of sodium phenobarbital on rat liver carcinogenesis.

The effects of S-methylcysteine (SMC) and cysteine on the promotion stages of rodent hepatocarcinogenesis in a medium-term bioassay previously developed by Ito were examined. Initiation was induced by a single dose of diethylnitrosamine (DEN), followed by dietary administration of the promoter sodium phenobarbital (NaPB) 2 weeks later, for 6 weeks. Partial hepatectomy was conducted on all the animals at week 3. Inhibitory potential was evaluated by analyzing two markers of carcinogenesis, namely numbers of glutathione S-transferase placental form (GST-P)-positive foci, and proliferating cell nuclear antigen (PCNA). In addition, the level of ornithine decarboxylase (ODC), one of the rate-limiting enzymes of polyamine metabolism induced by promoters, was analyzed. SMC and cysteine induced significant reduction in the areas of GST-P-positive foci. A significant reduction in the PCNA index was observed in the entire liver as well as in GST-P-positive areas. SMC also induced down-regulation of the ODC enzyme activity. Thus, SMC and cysteine were found to inhibit the promotion stage of DEN-induced hepatocarcinogenesis. No cocarcinogenic effects were evident on administration of either of these chemicals with NaPB.

Animals↗

Pharmacodynamics of S-2150, a simultaneous calcium-blocking and alpha1-inhibiting antihypertensive drug, in rats.

The in-vivo pharmacodynamics of S-2150, a newly developed dual-blocking type antihypertensive drug, was evaluated following intravenous infusion to rats. Previous in-vitro studies showed that the drug has two distinct mechanisms of antihypertensive effect--calcium-channel blocking activity and alpha1-adrenoceptor antagonism--which could be explained by a combination of two different pharmacodynamic models. The present in-vivo study showed that S-2150 also displays a complex pharmacodynamic profile (as measured by the decrease in mean blood pressure), which could be described by a combination of two sigmoid Emax models independently connected with the central compartment and the effect compartment. These results suggested that the dual-blocking mechanism of S-2150, which has been observed in in-vitro experiments, was also evaluated by the pharmacodynamic analysis of in-vivo experimental data.

Adrenergic alpha-1 Receptor Antagonists↗

Atypical aortic coarctation with resistant hypertension treated with axilloiliac artery bypass.

A 68-year-old woman was found to have atypical coarctation of the aorta, accompanied by systolic hypertension of the upper extremities despite administration of five types of antihypertensive drugs. Since the systolic hypertension was resistant to the conventional antihypertensive therapy, axilloiliac artery bypass grafting with a subcutaneous tunnel was performed to alleviate the pressure gradient. Systolic blood pressure was successfully reduced and hypertension was controlled after surgery.

Aged↗

A case of obesity, diabetes and hypertension treated with very low calorie diet (VLCD) followed by successful pregnancy with intrauterine insemination (IUI).

The patient was a 32-year-old obese woman with a history of type 2 diabetes and hypertension for 6 years. Although she was treated with antihypertensive agents and intensive insulin therapy, her hyperglycemia was difficult to control. She wanted to have a baby but pregnancy was not recommended because her diabetes was under poor control and the use of antihypertensive medication. To achieve good control of obesity, diabetes and hypertension, she was admitted to our clinical department for weight reduction using very low calorie diet (VLCD). During VLCD she had a 19.8 kg reduction in body weight and her blood glucose and blood pressure were in good control without the use of drugs. Five months later, she became pregnant after the fourth trial of intrauterine insemination (IUI) and gave birth to a female baby under insulin therapy. This is the first report that showed the usefulness of VLCD for prepregnant control of glucose metabolism and blood pressure in an obese hypertensive patient with type 2 diabetes mellitus.

Adult↗

Tumor-like splenic extramedullary hematopoiesis in a patient with myelofibrosis.

A 61-year-old woman, who was diagnosed in 1982 as having polycythemia vera, was admitted to our hospital in July 1998 because of a splenic tumor in an enlarged spleen due to myelofibrosis. As it was difficult to identify the etiology of the splenic tumor, partial splenectomy was carried out. The resected tumor proved to be an extremely proliferative lesion as the result of extramedullary hematopoiesis. Since it is difficult to diagnose the etiology of splenic tumor, the collection and analysis of reports of relevant cases may well facilitate diagnosis.

Diagnosis, Differential↗

[A case of alcoholic multiple nervous system degeneration].

Chronic ethyl alcohol abuse is associated with different types of neurological involvement. We report a 51-year-old woman with alcoholic encephalopathy, neuropathy and autonomic dysfunction. After the alcohol abuse of about thirty years, gait disturbance, dysphagia and dysarthria progressively worsened. We thought that the disease was caused by poor nutrition due to chronic alcohol abuse and vitamin B1, B12 deficiency. Her neurological symptoms and signs improved after discontinuation of alcohol and nutritional treatment.

Alcohol-Induced Disorders, Nervous System↗