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Biomedical subjects

Y Fujii

Publications and source records attributed to Y Fujii.

At least 37 records · Page 2Linked to original sources

Degradation pathways of cyclic alkanes in Rhodococcus sp. NDKK48.

The degradation pathways for cyclic alkanes (c-alkanes) in Rhodococcus sp. NDKK48 were investigated. Strain NDKK48 used dodecylcyclohexane as a sole carbon and energy source, and five metabolites in the dodecylcyclohexane degradation pathway were detected by gas-chromatography/mass spectra. The metabolites were identified as cyclohexanecarboxylic acid, cyclohexylacetic acid, 1-cyclohexene-1-acetic acid, 4-dodecylcyclohexanol, and 4-dodecylcyclohexanone. The strain degrades dodecylcyclohexane via a ring oxidation pathway and an alkyl side chain oxidation pathway. Cyclohexanecarboxylic acid was further oxidized to muconic acid via 1-cyclohexene-1-carboxylic acid and benzoic acid, and the muconic acid was finally used by strain NDKK48 for growth. Methylcyclohexane and cyclohexane were co-oxidized with hexadecane by strain NDKK48. Methylcyclohexane was degraded via a ring oxidation pathway, and the degradation pathway contained part of the Baeyer-Villiger oxidation for ring cleavage. Cyclohexane was also degraded by the same pathway as methylcyclohexane. Thus, strain NDKK48 has two pathways for the complete degradation of c-alkanes.

Biodegradation, Environmental↗

A randomized, double-blind, placebo-controlled trial of ramosetron for preventing nausea and vomiting during termination of pregnancy.

Women undergoing general anesthesia for dilatation and curettage have a high risk for postoperative nausea and vomiting. We therefore evaluated the efficacy and safety of ramosetron, a new compound having serotonin receptor antagonist activity, for preventing nausea and vomiting in termination of pregnancy. Eighty women scheduled for dilatation and curettage received, in a randomized, double-blind manner, an intravenous placebo or ramosetron at three different doses (0.15 mg, 0.3 mg, 0.6 mg) at the end of surgery (n = 20 per group). Emetic episodes and safety were assessed. The percentage of patients who were emesis-free (no nausea, no retching, no vomiting) during 0-24 h after anesthesia was 55% with ramosetron 0.15 mg (P = 0.5), 85% with ramosetron 0.3 mg (P = 0.02), and 90% with ramosetron 0.6 mg (P = 0.007), compared with 50% in the placebo group. No clinically serious adverse events due to the study drugs were observed in any group. Our results suggest that ramosetron 0.3 mg is an effective antiemetic for prophylaxis against emetic symptoms after dilatation and curettage. Increasing the dose to 0.6 mg provides no further benefit.

Abortion, Induced↗

Indometacin up-regulates TFF2 expression in gastric epithelial cells.

BACKGROUND: Trefoil factor family peptides are expressed in gastrointestinal epithelial cells and play a critical role in maintaining mucosal integrity. Although non-steroidal anti-inflammatory drugs (NSAIDs) are important causative agents of gastric mucosal lesions, few data are available about the effect of NSAIDs on trefoil family peptides in gastric mucosa. AIM: To examine whether indometacin, a widely used NSAID, affects trefoil factor family expression in gastric epithelial cells. METHODS: MKN45, a cell line derived from human gastric cancer, was used. TFF1, TFF2, and TFF3 mRNA expression was assessed by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). TFF2 gene transcription was also examined by luciferase reporter gene assay. RESULTS: Relative expression level of TFF1, TFF2, TFF3 mRNA was 616: 12: 1 in unstimulated MKN45 cells. Although indometacin (1-250 micro mol/L) had no significant effect on the expression of TFF1 and TFF3 mRNA, it up-regulated TFF2 mRNA expression in a dose- and time-dependent manner. Luciferase reporter gene assay confirmed the up-regulation of TFF2 gene transcription by indometacin. Indometacin-induced up-regulation of TFF2 expression was not antagonized by externally applied prostaglandin E2. CONCLUSION: These results suggest that indometacin up-regulates gastric epithelial cell TFF2 expression through a COX-independent mechanism. Since TFF peptides play an important role in gastric mucosal protection, indometacin-induced TFF2 may reduce the degree of gastric mucosal damage induced by indometacin.

Anti-Inflammatory Agents, Non-Steroidal↗

Intracerebroventricular administration of histamine H3 receptor antagonists decreases seizures in rat models of epilepsia.

The effects of histamine H3 antagonists on amygdaloid kindled and maximal electroshock seizures in rats were studied to determine their potential as new antiepileptic drugs. Under pentobarbital anesthesia, rats were fixed to a stereotaxic apparatus and a stainless steel guide cannula for drug administration was implanted into the lateral ventricle. In amygdaloid kindled seizures, electrodes were implanted into the right amygdala and electroencephalogram was recorded bipolarly; stimulation was applied bipolarly every day by a constant current stimulator and continued until a generalized convulsion was obtained. In the maximal electroshock (MES) seizure test, electroconvulsion was induced by stimulating animals through ear-clip electrodes, and the durations of tonic and clonic seizures were measured. Thioperamide, clobenpropit, iodophenpropit, VUF5514, VUF5515 and VUF4929 caused a dose-dependent inhibition of both seizure stage and afterdischarge (AD) duration of amygdaloid kindled seizures. The duration of tonic seizure induced by MES was also inhibited by H3 antagonists, but the duration of clonic seizures were unchanged. Among the H3 antagonists tested, clobenpropit and iodophenpropit were somewhat more potent than the other drugs on amygdaloid kindled seizures and MES seizures, respectively. These results indicate that some H3 antagonists may be useful as antiepileptic drugs, especially for secondary generalized seizures and/or tonic-clonic seizures in humans.

Amygdala↗

Effect of metoclopramide on pain on injection of propofol.

We undertook a randomized, double-blind, placebo-controlled study to examine the efficacy of metoclopramide at three different doses (2.5 mg, 5 mg, 10 mg) for reducing pain on injection of propofol in 100 patients scheduled for elective surgery. Patients received intravenously the study drug, with venous occlusion for one minute, followed by propofol 2 mg/kg into a dorsal hand vein. The incidence of pain was significantly less in patients receiving metoclopramide 5 mg (32%) or 10 mg (28%) than in patients receiving placebo (80%) (P<0.01). No difference between metoclopramide 2.5 mg and the placebo groups was found. We conclude that pretreatment of a dorsal hand vein with metoclopramide in a dose of 5 or 10 mg, with venous occlusion for one minute, effectively decreases the incidence of pain caused by propofol injection.

Adult↗

High resolution spectroscopy of the 12Lambda B hypernucleus produced by the (e,e'K+) reaction.

High-energy, cw electron beams at new accelerator facilities allow electromagnetic production and precision study of hypernuclear structure, and we report here on the first experiment demonstrating the potential of the (e,e'K+) reaction for hypernuclear spectroscopy. This experiment is also the first to take advantage of the enhanced virtual photon flux available when electrons are scattered at approximately zero degrees. The observed energy resolution was found to be approximately 900 keV for the (12)(Lambda)B spectrum, and is substantially better than any previous hypernuclear experiment using magnetic spectrometers. The positions of the major excitations are found to be in agreement with a theoretical prediction and with a previous binding energy measurement, but additional structure is also observed in the core excited region, underlining the future promise of this technique.

Journal Article↗

SAGE mRNA expression in advanced-stage lung cancers.

AIMS: SAGE and HAGE are recently isolated genes, which were thought to be expressed tumour-specifically, and are potentially coding for tumour-specific antigens recognized by T lymphocytes. The expression of these genes may serve as a useful diagnostic marker in detecting malignant disease. We report the correlation of SAGE and HAGE expression with clinicopathological features in patients with lung cancer who had undergone surgery. METHODS: Expression of SAGE and HAGE messenger RNA was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) in 102 lung carcinomas and adjacent histological normal lung samples using LightCycler. RESULTS: SAGE/GAPDH mRNA expression was not significantly different between the tumour of lung cancer tissue (3.777+/-10.802) and normal lung tissue (3.028+/-3.356, p=0.7283). There was no relationship between SAGE gene expression and age, gender or N-status. SAGE/GAPDH expression was significantly higher in stage III-IV lung cancer (6.180+/-16.475) than in stage I lung cancer (1.534+/-2.591, p=0.0393). SAGE/GAPDH expression was also significantly higher in T4 lung cancer (9.183+/-23.117) than in T2 lung cancer (2.676+/-5.943, p=0.0362) and T1 lung cancer (2.373+/-3.433, p=0.0371). CONCLUSIONS: Detection for SAGE mRNA expression is possible in lung cancer samples. There was no relationship between HAGE gene expression and clinicopathological factor, such that the usefulness of detection for HAGE mRNA expression is limited for lung cancer.

Antigens, Neoplasm↗

FHIT mRNA expression in thymoma.

AIMS: The FHIT gene is located at 3p14.2 a region frequently lost in multiple tumour types. Loss of FHIT expression has been found to occur frequently in multiple tumour types. We wished to investigate that FHIT mRNA levels in a series of thymomas. METHODS: Expression of FHIT messenger ribonucleic acid (RNA) was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) using a LightCycler in 49 thymomas and 11 adjacent histologically normal thymus samples from patients. RESULTS: FHIT transcripts in tumour samples (28.6+/-35.8) at levels significantly lower than those in normal thymus samples (573.9+/-1028.0, p=0.001). No relationship was seen between FHIT gene expression and age, gender, or pathological thymoma subtypes. FHIT mRNA expression in invasive thymomas (stage II-IV, 34.5+/-39.2) was significantly higher than that in stage I thymomas (20.7+/-29.7, p=0.01). Immunohistochemistry showed that p21 protein positive thymoma had a tendency towards higher FHIT gene expression than in p21 negative thymoma. CONCLUSIONS: Decreased FHIT expression might be seen in early stage thymoma, suggesting that loss of FHIT expression may associate with tumorigenesis of thymoma.

Acid Anhydride Hydrolases↗

Clinical significance of tissue inhibitor of metalloproteinase and matrix metalloproteinase mRNA expression in thymoma.

BACKGROUND: Matrix metalloproteinases (MMPs) are proteolytic enzymes which degrade extracellular matrix and basement membrane. There is much evidence that their increased expression is correlated with tumor aggressiveness in various carcinomas. Tissue inhibitor of metalloproteinases (TIMPs) are the specific inhibitors of MMPs. MMPs and TIMPs are considered to play an important role in carcinoma invasion and metastasis. We hypothesized that MMPs and TIMPs also play an important role in thymoma. MATERIALS AND METHODS: This study included 34 thymoma cases. The mRNA levels of MMP-1, -7, and -9, TIMP-1 and -2, and GAPDH were quantified by real-time polymerase chain reaction using LightCycler. We also performed immunohistochemistry for TIMP-1. RESULTS: The TIMP-1/GAPDH mRNA expression level was significantly higher in invasive (stage II-IV) thymomas (means +/- SE, 81.4 +/- 28.1) than in noninvasive (stage I) thymomas (30.9 +/- 8.3, P = 0.026). The MMP-1/GAPDH mRNA expression level was also higher in invasive thymomas (19.7 +/- 7.5) than in non invasive thymomas (2.26 +/- 1.72, P = 0.020). Immunopositivity of TIMP-1 was localized in stromal cells adjacent to the advancing margin of the tumor. CONCLUSIONS: These findings suggest that TIMPs and MMPs play an important role in the invasion of thymoma.

Gene Expression↗

Role of AMPA and NMDA receptors in the nucleus accumbens shell in turning behaviour of rats: interaction with dopamine receptors.

The role of AMPA and NMDA receptors in the shell of the nucleus accumbens in turning behaviour of rats was investigated. Unilateral injection of the AMPA receptor agonist, AMPA (0.25, 0.4, 0.5 and 1 microg), into the shell of the nucleus accumbens dose-dependently produced contraversive pivoting, namely tight head-to-tail turning marked by abnormal hindlimb backward stepping, while injection of AMPA (0.5 microg) into the core produced only a marginal effect. This shell-specific AMPA effect was dose-dependently inhibited by the AMPA receptor antagonist, NBQX (1 and 10 ng), which alone did not produce turning behaviour. The AMPA-induced pivoting was also dose-dependently inhibited by the non-competitive NMDA receptor antagonist, MK-801 (0.1 and 0.5 microg). Neither MK-801 (0.1, 0.5 and 5 microg) nor the NMDA receptor agonist, NMDA (0.5 and 1 microg), injected unilaterally into the shell, produced turning behaviour. Unilateral injection of a mixture of dopamine D(1) (SKF 38393, 5 microg) and D(2) (quinpirole, 10 microg) receptor agonists into the shell has been found to elicit contraversive pivoting. The dopamine D(1)/D(2) receptor antagonist, cis-(Z)-flupentixol (1 and 10 microg), injected into the shell, in doses known to block dopamine D(1)/D(2) receptor-mediated pivoting, also significantly inhibited AMPA (0.5 microg)-induced pivoting. Moreover, both NBQX (1 and 10 ng) and MK-801 (0.1 and 0.5 microg), injected into the shell, significantly inhibited dopamine D(1)/D(2) receptor-mediated pivoting. It is therefore concluded that unilateral stimulation of AMPA receptors in the shell of the nucleus accumbens can elicit contraversive pivoting, and that both AMPA and dopamine D(1)/D(2) receptors play a critical role in shell-specific pivoting in contrast to NMDA receptors that at best play only a modulatory role.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Association of fulminant type 1 diabetes with pregnancy.

It has been reported that fulminant type 1 diabetes is a novel subtype of type 1B diabetes. However, whether the etiology of fulminant type 1 diabetes is associated with an autoimmune or nonautoimmune process remains to be solved. In order to further characterize fulminant type 1 diabetes, we compared the clinical, immunological and genetic characteristics with those of acute-onset type 1A diabetes. Nine patients with fulminant diabetes and nine patients with acute-onset type 1A diabetes, who had been newly diagnosed during 1998-2001, were analyzed. In female patients of child-bearing age, the onset of diabetes occurred during pregnancy or after delivery in three cases of six fulminant cases, but not in any of seven type 1A diabetes. Eight of nine fulminant patients had fever immediately prior to the onset of hyperglycemic symptoms, whereas only one of nine type 1A patients had this (P=0.002). In Japanese type 1 susceptible HLA haplotypes, DRB1*0901-DQB1*0303 was more frequent in type 1A diabetes than fulminant diabetes (7/18 vs. 0/18, P=0.004), whereas the frequency of DRB1*0405-DQB1*0401 was similar (type 1A 4/18 vs. fulminant 6/18). Therefore, pregnancy, possible viral infection, or HLADRB1*0405-DQB1*0401 may contribute to the onset of fulminant type 1 diabetes.

Adult↗

Angioarrestin mRNA expression in early-stage lung cancers.

AIMS: Angioarrestin is a recently isolated gene, which has a novel function as an angiogenesis inhibitor. Angiogenesis plays an important role in tumorigenesis. It has been reported that the angioarrestin expression was decreased in lung cancer. We attempted to determine the influence of angioarrestin expression on clinicopathological features in patients with lung cancer who had undergone surgery. METHODS: Expression of angioarrestin messenger RNA was evaluated by a quantitative reverse transcription-polymerase chain reaction (RT-PCR) in 93 lung carcinomas and adjacent histological normal lung samples using LightCycler. RESULTS: Angioarrestin/GAPDH mRNA expression was significantly decreased in the tumor of lung cancer tissue (86.676+/-123.505) than in the normal lung tissue (1154.218+/-2003.508, p<0.0001), although only four lung cancer tissues had more than one tumor/normal ratio of angioarrestin/GAPDH mRNA expression. There was no relationship between angioarrestin gene expression and age, gender or T-status. However, decreased angioarrestin/GAPDH expression was especially seen at stage I lung cancer (54.156+/-62.783) when compared to stage II-IV lung cancer (110.315+/-151.359, p=0.0316). Decreased angioarrestin/GAPDH expression was especially seen at N0 lung cancer (56.396+/-69.941) when compared to N2 lung cancer (137.522+/-180.489, p=0.0362). CONCLUSIONS: The decreased expression of angioarrestin mRNA was the early phase phenomena for tumor progression from lung cancer. Alternatively, loss of antianiogenesis might play a role in oncogenesis for lung cancer.

Angiopoietin-Like Protein 1↗

Endostatin gene therapy on murine lung metastases model utilizing cationic vector-mediated intravenous gene delivery.

Tumors require ongoing angiogenesis to support their growth. Inhibition of angiogenesis by production of antiangiogenic factors should be a viable approach for cancer gene therapy. In this study, we investigated whether intravenous administration of endostatin gene complexed with a cationic vector (GL67/DOPE or PEI22K) could inhibit the development of lung tumors in mice injected i.v. with NFSa Y83 fibrosarcoma cells (5 x 10(5)) which frequently form lung metastasis. mRNA and protein of the transfected gene were produced in the lung and other organs of the transfected mice as assessed by immunohistochemistry, Western blotting and reverse transcription-polymerase chain reaction. Single intravenous injection of the endostatin gene (60 microg) complexed with either GL67/DOPE or PEI22K on day 3 or day 7 after fibrosarcoma cell inoculation significantly inhibited tumor formation in the lung as evidenced by the reduced number of lung tumors and lung weight, and prolonged survival of the endostatin gene-transfected mice compared with control mice. These findings suggested that the endostatin gene therapy, using cationic vector-mediated intravenous gene transfer, might be a feasible strategy for organ-targeted prevention and regulation of possible disseminated cancers.

Animals↗

Long-term outcome of bladder papillary urothelial neoplasms of low malignant potential.

OBJECTIVE: To evaluate the long-term outcome of bladder papillary urothelial neoplasms of low malignant potential (PUNLMP). PATIENTS AND METHODS: Of 475 consecutive patients with newly diagnosed bladder tumours between 1976 and 1993, 330 (69%) had superficial (Ta and T1) tumours and 53 (11%) were diagnosed as having PUNLMP. Fifty patients (mean age at presentation 57.2 years, range 26-83; male-to-female ratio 6 : 1) who were followed for> 5 years or until they died, were included in the present study. All histological slides were reviewed, and fulfilled the diagnostic criteria of the 1998 World Health Organization/International Society of Urological Pathology classification system. RESULTS: The mean (median, range) follow-up was 11.7 (10.8, 1.3-24.4) years. During the follow-up, 30 patients (60%) had local recurrences. The 2, 5 and 10-year recurrence-free rates were 66%, 51% and 36%, respectively. No patients developed high-grade or muscle-invasive (>/= T2) carcinomas, or upper urinary tract tumours, or died from the disease. At the last follow-up, 34 patients (68%) had been disease-free for> 5 years. CONCLUSIONS: Despite a high recurrence rate, PUNLMP carries a very low malignant potential. We agree with the use of the term 'papillary urothelial neoplasms of low malignant potential' instead of 'superficial bladder carcinoma (cancer)' for these tumours.

Adult↗

Expression of Id2 mRNA in neuroblastoma and normal ganglion.

AIMS: Inhibitors of DNA binding 2 (Id2) has been reported to be overexpressed in neuroblastoma cell lines carrying extra copies of the N-myc gene. It has been suggested that Id2 may be involved in the disturbed regulation of cell cycle by interfering with retinoblastoma protein. METHODS: In this report we assessed Id2 gene expression in 20 neuroblastoma samples and eight normal ganglion tissues using quantitative reverse transcription-PCR (RT-PCR). Id2 expression in resected clinical samples of neuroblastoma needs to be studied. RESULTS: Id2 messenger RNA (mRNA) was expressed in all the neuroblastoma samples. The level of Id2 mRNA expression was not influenced by the patient's age, gender, tumor's clinical stage, DNA ploidy pattern, histological pattern, the level of N-myc mRNA expression and whether the patient was found by mass screening or by symptom. Id2 was also expressed in comparable levels in normal differentiated sympathetic ganglion in adult. CONCLUSION: Our data suggest that Id2's role in the oncogenesis or progression of neuroblastoma is minimal.

DNA-Binding Proteins↗