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Y Hori

Publications and source records attributed to Y Hori.

At least 55 records · Page 3Linked to original sources

In vitro hyperprocessing of tRNAs by Bacillus subtilis ribonuclease P RNA.

We have previously reported that the catalytic RNA subunit of ribonuclease P (RNase P) of Escherichia coli (M1 RNA) cleaves Drosophila initiator methionine tRNA (tRNA(i)Met), alanine tRNA (tRNA(Ala)) and histidine tRNA (tRNA(His)) within the mature tRNA sequences to produce specific fragments. We call this further cleavage hyperprocessing. These cleavages were dependent on the occurrence of altered conformations of the tRNAs. Here, we found that the RNase P RNA of Bacillus subtilis can hyperprocess these three tRNAs at the same sites as does M1 RNA. The hyperprocessing activity may probably be common feature for Bacterial RNase P RNAs.

Animals↗

Therapeutic time-window of a group IIA phospholipase A2 inhibitor in rabbit acute lung injury: correlation with lung surfactant protection.

OBJECTIVE: We attempted to determine whether group IIA secretory phospholipase A2 (sPLA2-IIA) blockade after the onset of lung injury exerted therapeutic efficacy in the treatment of oleic acid (OA)-induced acute lung injury by using S-5920/LY315920Na, a novel specific inhibitor of sPLA2-IIA, with special interest in the changes of lung surfactant. DESIGN: Prospective animal study. SETTING: University laboratory. SUBJECTS: Forty Japanese white rabbits. INTERVENTIONS: The rabbits, under anesthesia, were endotracheally intubated and mechanically ventilated and then were divided into the following groups: OA + vehicle groups, intravenous infusion of OA for the first 2 hrs (0.1 mL x kg(-1) x hr(-1)) with the addition of vehicle (1 or 2 hrs after OA administration, each n = 9, total 18 rabbits); OA + S-5920/LY315920Na groups, treated identically to the OA control with the addition of S-5920/LY315920Na (1 mg/kg bolus followed by infusion at 0.5 mg x kg(-1) x hr(-1)) after OA (1 or 2 hrs after OA administration, each n = 9, total 18 rabbits); saline control groups, treated with saline instead of OA with the addition of vehicle (1 hr after OA administration, 4 rabbits). Arterial blood gas, lung mechanics, lung inflammation, lung surfactant phospholipids, and production of inflammatory mediators in the lung were measured. MEASUREMENTS AND MAIN RESULTS: Treatment with S-5920/LY315920Na 1 hr after OA infusion, but not 2 hrs after infusion, significantly attenuated the lung injury, as estimated by hypoxemia, decreased lung compliance, pulmonary edema, and vascular permeability. The therapeutic efficacy was similar to that found in our previous pretreatment study. The treatment after 1 hr dramatically inhibited OA-induced surfactant degradation in the bronchoalveolar lavage fluid (BALF), without affecting the concentrations of thromboxane A2, leukotriene B4, and interleukin-8 in BALF. The degree of surfactant degradation in BALF paralleled well with the severity of the lung injury. Furthermore, recombinant human sPLA2-IIA reproduced the similar hydrolysis pattern of isolated surfactant in vitro, which was inhibited by S-5920/LY315920Na. CONCLUSIONS: Our results indicate that therapeutic blockade of sPLA2-IIA ameliorated lung dysfunction via protection of surfactant degradation in an animal model of acute lung injury, and they suggest a new strategy in treating clinical acute lung injury.

Acetates↗

Plasma levels of agouti-related protein are increased in obese men.

To investigate the relationship between peripheral blood levels of agouti-related protein (AGRP) and various parameters of obesity, we measured the plasma level of AGRP in 15 obese and 15 nonobese men and evaluated its relationship with body mass index (BMI), body fat weight, and visceral, sc, and total fat areas measured by computed tomography, fasting insulin levels, glucose infusion rate during an euglycemic hyperinsulinemic clamp study, serum leptin, and plasma alpha-MSH. Obese men had significantly higher plasma concentrations of AGRP than nonobese men (P < 0.01). Univariate analysis showed that the plasma levels of AGRP are proportionally correlated with BMI, body fat weight, and sc fat area in obese men (BMI: r = 0.732, P < 0.01; body fat weight: r = 0.603, P < 0.02; sc fat area: r = 0.668, P < 0.01) and in all men (BMI: r = 0.839, P < 0.0001; body fat weight: r = 0.818, P < 0.0001; sc fat area: r = 0.728, P < 0.0001). In all men, the plasma levels of AGRP were significantly correlated with the visceral fat area (r = 0.478, P < 0.01), total fat area (r = 0.655, P < 0.0001), fasting insulin level (r = 0.488, P < 0.01), glucose infusion rate (r = -0.564, P < 0.01), serum level of leptin (r = 0.661, P < 0.0001), and the plasma level of alpha-MSH (r = 0.556, P < 0.01). In all subjects, multiple regression analysis showed that the plasma levels of AGRP are significantly (F = 15.522, r = 0.801, P < 0.03) correlated with the plasma levels of alpha-MSH, independently from the total fat area. However, the correlation between plasma levels of AGRP and serum levels of leptin was found to be dependent on the total fat area. In brief, these findings showed that the circulating levels of AGRP are increased in obese men and that they are correlated with various parameters of obesity. Although correlation does not prove causation, the results of this study suggest that peripheral AGRP may play a role in the pathogenesis of obesity.

Adult↗

Effects of chondroitin sulfate on colitis induced by dextran sulfate sodium in rats.

Chondroitin sulfate (CS) is currently marketed as a therapeutic drug for neurodynia, lumbago and arthrodynia. Recently, many clinical studies have demonstrated the therapeutic effects of orally administered CS against diseases with inflammation. Furthermore, these reports suggest CS plays an important role in the protection of the base of ulcers and has anti-inflammatory activity. We investigated the effects of CS against dextran sulfate sodium (DSS)-induced rat colitis. Rats were given 3% DSS solution for 10 days ad libitum. CS and 5-aminosalicylic acid (5-ASA) were orally administered daily. The doses of the CS groups were 20 or 100 mg/kg and that for the 5-ASA group was 100 mg/kg. Evaluations were made of bloody stools, areas of erosion and hematological data. CS improved the symptoms of bloody stools, erosion and increase of white blood cells. Especially, CS (100 mg/kg) group showed markedly more improvement than the 5-ASA group. We think that the major mechanism of the therapeutic effects of CS are the prevention of tissue damage by the protection of digestive mucosa and anti-inflammatory effects. Therefore, CS may have therapeutic value for alimentary tract diseases such as inflammatory bowel disease or ulcer.

Animals↗

Human tyrosine tRNA is also internally cleavable by E. coli ribonuclease P RNA ribozyme in vitro.

Transfer RNA is an essential molecule for biological system, and each tRNA molecule commonly has a cloverleaf structure. Previously, we experimentally showed that some Drosophila tRNA (tRNA(Ala), tRNA(His), and tRNA(iMet)) molecules fit to form another, non-cloverleaf, structure in which the 3'-half of the tRNA molecules forms an alternative hairpin, and that the tRNA molecules are internally cleaved by the catalytic RNA of bacterial ribonuclease P (RNase P). Until now, the hyperprocessing reaction of tRNA has only been reported with Drosophila tRNAs. This time, we applied the hyperprocessing reaction to one of human tRNAs, human tyrosine tRNA, and we showed that this tRNA was also hyperprocessed by E. coli RNase P RNA. This tRNA is the first example for hyperprocessed non-Drosophila tRNAs. The results suggest that the hyperprocessing reaction can be a useful tool detect destablized tRNA molecules from any species.

Base Sequence↗

Homeostasis model assessment is a reliable indicator of insulin resistance during follow-up of patients with type 2 diabetes.

OBJECTIVE: To investigate the usefulness of the homeostasis model assessment as an index of insulin resistance (HOMA-IR) for evaluating the clinical course of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The usefulness of HOMA-IR and its relationship with insulin resistance assessed by the hyperinsulinemic-euglycemic clamp study (clamp IR) were evaluated in 55 Japanese patients with type 2 diabetes before and after treatment. The patients were subjected to diet (approximately 1,440-1,720 kcal/day) and exercise therapy (walking 10,000 steps daily) for 6 weeks during their hospitalization. RESULTS: Univariate regression analysis disclosed a significant correlation between log-transformed HOMA-IR and log-transformed clamp IR before (r = -0.613, P < 0.0001) and after ( = -0.734, P < 0.0001) treatment. Neither the slopes (-0.71 +/- 0.12 vs. -0.79 +/- 0.09, F = 0.25, P = 0.61) nor the intercepts (y-intercept = 1.67 vs. 1.70, x-intercept = 2.36 vs. 2.15, F = 0.02, P = 0.88) of the regression lines between HOMA-IR and clamp IR were significantly different before and after treatment. There was a significant correlation between the decrease in log-transformed HOMA-IR and the increase in clamp IR during treatment (r = -0.617, P < 0.0001). CONCLUSIONS: HOMA-IR may constitute a useful method not only for diagnosing insulin resistance, but also for follow-up during the treatment of patients with type 2 diabetes.

Adult↗

[Significance of CT findings and catecholamine determination in peripheral blood of asymptomatic pheochromocytoma and paraganglioma].

The purpose of this study was to assess the CT findings and significance of hormone determination in the peripheral blood of asymptomatic patients with pheochromocytoma and paraganglioma. CT findings in 29 patients with surgically proven pheochromocytoma(n = 19) and paraganglioma(n = 10) were reviewed. Nine patients(31%) were symptomatic and 20 (69%) were asymptomatic. Tumor size ranged from 39 mm to 114 mm(mean: 60 mm) in symptomatic patients and 11 mm to 100 mm(mean: 50 mm) in asymptomatic ones. Of the 9 symptomatic patients and 18 asymptomatic patients, a homogeneous solid pattern was seen in 4 and 4, mixed pattern in 2 and 6, and massive necrotic pattern in 3 and 8 patients, respectively, on CT scans. The CT attenuation values in symptomatic cases ranged from 30 HU to 50 HU(mean: 41 HU) on precontrast CT scans and 60 HU to 111 HU(mean: 77 HU) on postcontrast CT scans, while those in asymptomatic cases ranged from 15 HU to 48 HU(mean: 33 HU) on precontrast CT scans and 66 HU to 133 HU(mean: 95 HU) on postcontrast CT scans. There were no statistically significant differences in tumor size, homogeneity, or CT attenuation values between symptomatic and asymptomatic patients. All symptomatic patients and 17(89%) of 19 asymptomatic cases showed elevated levels of catecholamine (epinephrine) or norepinephrine in the peripheral blood. Our study showed that the CT findings in asymptomatic patients were similar to those in symptomatic patients, and 89% of asymptomatic patients showed elevation of catecholamine in the peripheral blood. Determination of catecholamine level in the peripheral blood is recommended for preoperative diagnosis in patients suspected of having asymptomatic pheochromocytoma or paraganglioma on CT scans.

Adrenal Gland Neoplasms↗

Tissue engineering of the small intestine by acellular collagen sponge scaffold grafting.

Tissue engineering of the small intestine will prove a great benefit to patients suffering from short bowel disease. However cell seeding in tissue engineering, such as fetal cell use, is accompanied by problems of ethical issues, rejection, and short supply. To overcome these problems, we carried out an experimental study on tissue engineering of the small intestine by acellular collagen sponge scaffold grafting. We resected the 5 cm long jejunum from beagle dogs and reconstructed it by acellular collagen sponge grafting with a silicon tube stent. The graft was covered with the omentum. At 1 month after operation, the silicon stent was removed endoscopically. Animals were sacrificed 1 and 4 months after operation, and were examined microscopically. Neo-intestinal regeneration was observed and the intestinal mucosa covered the luminal side of the regenerated intestine across the anastomosis. Thus, the small intestine was regenerated by tissue engineering technology using an acellular collagen sponge scaffold.

Animals↗

[Effects of topical prostaglandin analogues on the aqueous flare intensity in rabbit eyes at an early phase of endotoxin-induced uveitis].

PURPOSE: We examined the effects of prostaglandin analogues on the blood-aqueous barrier(BAB) permeability in rabbit eyes at an early phase of endotoxin-induced uveitis(EIU). SUBJECTS AND METHODS: One drop of 0.005% latanoprost or 0.12% unoprostone were applied to rabbit eyes. Escherichia coli lipopolysaccharides were injected to induce uveitis. The changes in flare intensity in normal eyes and EIU eyes after application of eye drops were evaluated. The effect of cyclooxygenase inhibitor on the flare intensity changes caused by the application of unoprostone was also examined. RESULTS: Flare intensity increased significantly after a single instillation of unoprostone, and the increase was not prevented by pretreatment with cyclooxygenase inhibitor. In eyes with EIU, unoprostone caused an additional increase of flare intensity to uveitis induced flare change. Latanoprost had no effects on BAB in eyes with normal and with uveitic conditions. CONCLUSION: Latanoprost and unoprostone did not cause an excessive inflammatory reaction in rabbit eyes at an early phase of EIU.

Animals↗

The effect of TGF-beta1 on differential gene expression profiles in human corneal epithelium studied by cDNA expression array.

PURPOSE: TGF-betas regulate cell proliferation and differentiation, and they play important roles in maintenance of corneal epithelium. However, the precise function of TGF-betas in the corneal epithelium remains unclear. In this study, cDNA expression array technology was used to demonstrate the effect of TGF-beta1 on the simultaneous expression of a large number of genes in cultured human corneal epithelial cells (HCECs). The change in protein level expression of the specific genes influenced by TGF-beta1 was also investigated. METHODS: Human cDNA expression array technology was used to study the simultaneous expression of 1176 specific cellular genes in HCECs incubated with TGF-beta1 (10 ng/ml). Moreover, gene-specific semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to confirm the gene expression pattern measured by the cDNA expression array. Western blot analysis was used to examine protein expression of the specific genes in the presence or absence of TGF-beta1. RESULTS: TGF-beta1 significantly upregulated the expression of 19 genes and significantly downregulated ras-related protein, caspase10, and beta4-integrin in the treated HCECs. The expression of 277 genes including alpha3-integrin, PAI-2, transferrin receptor, and cyclin-D1 was studied. Semiquantitative RT-PCR analysis confirmed the TGF-beta1-mediated changes in expression patterns of these genes. Furthermore, Western blot analysis revealed that TGF-beta1 remarkably decreased PAI-2, transferrin receptor, and integrin alpha3, and increased caspase10 on the protein level. CONCLUSIONS: TGF-beta1 regulates the expression of specific types of genes in HCECs. These results strongly suggest that TGF-beta1 is critically involved in the maintenance of the corneal epithelium through the control of a network of various signal-transduction pathways.

Blotting, Western↗

[Determination of 4-O-methylpyridoxine (MPN) by HPLC with diode-array detector].

We have developed a simple and rapid method for measuring 4-O-methylpyridoxine (MPN) in the serum of an acute poisoning patient by high-performance liquid chromatograph (HPLC) with a diode-array detector. MPN, a poisonous ingredient of ginkgo seeds was extracted using an Isolute C18 solid-phase extraction column. Equal volumes of the extract were injected into a C18 HPLC column using acetonitrile-10 mM phosphate buffer (pH 3) as the mobile phase. Excellent linearity was obtained over the range of 1-1000 ng at a wavelength of 290 nm, and its detection limit of approximately 0.5 ng was considered to be satisfactory. The mean recovery of MPN in the serum was 92.9 +/- 6.1%. The method was used successfully in a case of acute poisoning.

Chromatography, High Pressure Liquid↗

[A case of fatal acute sodium azide poisoning].

A case of fatal sodium azide poisoning induced by suicidal ingestion was reported. When the patient arrived, her vital signs such as consciousness and blood pressure, were normal. But 25 hours after ingestion, she died from metabolic acidosis, ARDS (acute respiratory distress syndrome) and acute cardiac failure. We detected the azide ion in patient's serum using GCMS method and measured the blood concentration of sodium azide using the GC/NPD method. The half-life period of sodium azide in blood was calculated as about 2.5 hours.

Acidosis↗

[A case of carbamate poisoning in which GCMS was useful to identify causal substance and to decide the appropriate treatment].

We often have cases of insecticide poisoning where the patient is unconscious and the causal substances are unknown. We report an 83-year-old unconscious man who had apparently ingested several agricultural chemicals, possibly organophosphate or carbamate. According to his family, there were three kinds of containers of agricultural chemicals with their caps opened around him. When he was transferred to our hospital, he presented hypertension, hypersalivation, and muscle fasciculation. His pupils were markedly miotic. In order to identify the substances ingested we used a gas chromatographymass spectrometer (GCMS) using his gastric content. Within 30 minutes we were able to identify the causal substance as methomyl, one of the popular carbamates, thereby eliminating the need to use pralidoxime (PAM). GCMS makes it possible to identify unknown substances quickly and accurately and is therefore extremely useful in deciding the appropriate treatment.

Aged↗

Intravenous nedaplatin and intraarterial cisplatin with transcatheter arterial embolization for patients with locally advanced uterine cervical cancer.

Nedaplatin is a platinum analog that has less renal toxicity and higher efficacy for uterine cervical cancer than cisplatin. Intraarterial cisplatin has been shown to be more effective than intravenous cisplatin in the treatment of cervical cancer. To improve the prognosis of cervical cancer, we studied combination chemotherapy of intravenous nedaplatin and intraarticular cisplatin with transcatheter arterial embolization (TAE). The criteria for selecting patients for this study were as follows: age 16-75 years, stage Ib2-IV according to the classification of the International Federation of Gynecology and Obstetrics (FIGO), performance status between 0 and 2, a creatinine clearance of >40 ml/min, adequate bone marrow and adequate renal and hepatic function. Thirty-two patients, aged 29-72 years (median: 55) were treated. FIGO stage was Ib2 in seven patients, IIa in seven patients, IIb in four, IIIa in one, IIIb in seven and IVa in six. Twenty-four patients had squamous cell carcinoma, three had adenocarcinoma and five had adenosquamous carcinoma. Written informed consent was obtained from all patients. Nedaplatin (30-70 mg/m2) was administered intravenously on day 1 and cisplatin (70 mg/m2) was administered intraarticularly via both uterine arteries on day 3 using the Seldinger method. TAE was then performed. This course of treatment was repeated every 3 weeks for 2-3 cycles. Response to the therapy was defined by magnetic resonance imaging. Partial response was found in 59% patients (19/32) and complete response in 34% (11/32), with an overall response rate of 94% (30/32). Myelosuppression was manageable. No grade 2 neurotoxicity was observed. The median follow-up was 32 months (6-53 months), with 84% of patients showing an overall survival of 1 year and 77% showing an overall survival of 2 years. These results show that this combination chemotherapy effected a high response rate. However, its influence on long-term survival remains to be determined.

Adenocarcinoma↗

Well maintained expression of CYP genes in sandwich-culturing hepatocytes: quantitative analysis using real-time PCR method.

Sandwich-culturing is an excellent hepatocyte culturing method in drug metabolism studies, however, its advantages for gene expression of cytochrome P450 (CYP) have not been evaluated so far. The present study was undertaken to determine the utilities of sandwich-culturing hepatocytes for evaluation of CYP genes expression. Hepatocytes from male rats were cultured for 5 days between two layers of type-I collagen gel (sandwich-culturing) or over type-I collagen gel (single gel culturing). To determine the expression of CYP genes rapidly and accurately, the time course study using real-time RT-PCR quantification was conducted in the present study, and CYP2B1, CYP2B2, CYP3A2, CYP3A9 and CYP3A23 genes were measured. Albumin secretion was also measured by ELISA to evaluate cell viability. Higher expression and excellent maintenance of all CYP genes were confirmed in sandwich-culturing hepatocytes than those in single gel culturing. Particularly, significant difference in the amounts of CYP genes expression was observed between both methods after 3 days culturing. Albumin secretion was also higher in sandwich-culturing after 3 days culturing, suggesting that the cell viability of hepatocytes was maintained. These results indicate that sandwich-culturing method is much more advantageous than the ordinate method in maintaining the CYP gene expression and cell viability.

Animals↗