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Biomedical subjects

Y Inoue

Publications and source records attributed to Y Inoue.

At least 55 records · Page 3Linked to original sources
PubMed2004

Inhibition of the metabolism of etizolam by itraconazole in humans: evidence for the involvement of CYP3A4 in etizolam metabolism.

OBJECTIVE: To clarify the involvement of cytochrome P450 (CYP) 3A4 in the metabolism of etizolam. METHODS: The effects of itraconazole, a potent and specific inhibitor of CYP3A4, on the single oral dose pharmacokinetics and pharmacodynamics of etizolam were examined. Twelve healthy male volunteers received itraconazole (200 mg/day) or placebo for 7 days in a double-blind randomized crossover manner, and on the 6th day they received a single oral 1-mg dose of etizolam. Blood samplings and evaluation of psychomotor function using the Digit Symbol Substitution Test and Stanford Sleepiness Scale were conducted up to 24 h after etizolam dosing. Plasma concentration of etizolam was measured by means of high-performance liquid chromatography. RESULTS: Itraconazole treatment significantly increased the total area under the plasma concentration-time curve (AUC; 213+/-106 ng rectangle h/ml versus 326+/-166 ng rectangle h/ml, P<0.001) and the elimination half-life (12.0+/-5.4 h versus 17.3+/-7.4 h, P<0.01) of etizolam. The 90% confidence interval of the itraconazole/placebo ratio of the total AUC was 1.38-1.68, indicating a significant effect of itraconazole. No significant change was induced by itraconazole in the two pharmacodynamic parameters. CONCLUSION: The present study suggests that itraconazole inhibits the metabolism of etizolam, providing evidence that CYP3A4 is at least partly involved in etizolam metabolism.

Adult↗
PubMed2004

Rapid and sensitive screening for and chemical diagnosis of Canavan disease by gas chromatography-mass spectrometry.

The use of a rapid and sensitive assay for N-acetylaspartate (NAA) in urine or eluates from dried urine on filter paper to make a chemical diagnosis of Canavan disease (CD) is described. It involves a simplified urease pretreatment for sample preparation and gas chromatography-mass spectrometry (EI, scanning mode) with or without stable isotope dilution. Significant improvements in the recovery of NAA and the GC-MS data-handling device made the assay without stable isotope dilution sensitive and quantitative enough to diagnose CD: Its coefficient of variation (CV) was below 12%. The CV obtained with stable isotope dilution was below 9%. One patient with CD had an abnormal NAA level that was more than 6 S.D. above the mean of the age-matched controls. This diagnostic procedure is accurate for screening and for the chemical diagnosis of CD, with a good cost:benefit ratio. The urinary NAA levels of the healthy controls decreased significantly with age. This change should be considered in making a chemical diagnosis of this disease.

Aspartic Acid↗
PubMed2004

Anti-monocyte chemoattractant protein-1 gene therapy attenuates nephritis in MRL/lpr mice.

OBJECTIVE: Monocyte chemoattractant protein-1 (MCP-1) is up-regulated and recruits and activates inflammatory cells in human diffuse proliferative lupus nephritis (DPLN) and in nephritis of lupus model MRL/lpr mice. The aim of this study was to examine whether anti-MCP-1 gene therapy inhibits the progression of nephritis in MRL/lpr mice. METHOD: An NH(2)-terminal deletion mutant of the MCP-1 gene, 7ND, was injected into skeletal muscles of MRL/lpr mice with advanced stage nephritis to blockade MCP-1 and its receptor (CCR2) signalling pathway. RESULT: Histological findings of kidneys in treated mice, which received more than four injections of 7ND, showed that protection against renal injury resulted from reduced infiltration of leucocytes. Therefore, this therapy has been shown to prolong the life span of MRL/lpr mice. CONCLUSION: Anti-MCP-1 gene therapy is specifically effective in the localized inflammatory region. The data presented here indicate that this anti-MCP-1 gene therapy may be effective adjunct in the management of DPLN.

Animals↗
PubMed2004

A novel antipsychotic, perospirone, has antiserotonergic and antidopaminergic effects in human brain: findings from neuroendocrine challenge tests.

RATIONALE: Perospirone is a new antipsychotic drug in which dopamine D(2) antagonist and serotonin 5-HT(2) antagonist effects have been found in animal studies. It was developed by a Japanese pharmaceutical company and launched in 2001. Perospirone's receptor binding profile may resemble that of atypical antipsychotic drugs, but to date there has been no evidence relating to its receptor binding affinity in the human brain. OBJECTIVE: The purpose of this study was to investigate the receptor binding profile of perospirone via neuroendocrine challenge tests. METHODS: Twenty subjects (ten females and ten males) were tested on four occasions in a double-blind, cross-over design receiving: (a) placebo, (b) perospirone 4 mg, (c) paroxetine 20 mg, and (d) paroxetine 20 mg plus perospirone 4 mg, administered orally at 8.00 a.m. Plasma cortisol and prolactin levels were measured prior to administration and every hour for 6 h thereafter. In addition, psychological responses rated by visual analog scales and vital signs such as body temperature, pulse, and blood pressure were assessed in combination with blood sampling. RESULTS: Perospirone 4 mg increased prolactin levels significantly higher than placebo, whereas paroxetine 20 mg plus perospirone 4 mg significantly attenuated cortisol responses induced by paroxetine 20 mg. CONCLUSIONS: The present findings suggest that perospirone has the characteristics of both D(2) and 5-HT(2) antagonist in the human brain. Further PET studies in the human brain are required in order to directly investigate these effects.

Adult↗
PubMed2004

Achievement of ultralow emittance beam in the accelerator test facility damping ring.

For high luminosity in electron-positron linear colliders, it is essential to generate low vertical emittance beams. We report on the smallest vertical emittance achieved in single-bunch-mode operation of the Accelerator Test Facility, which satisfies the requirement of the x-band linear collider. The emittances were measured with a laser-wire beam-profile monitor installed in the damping ring. The bunch length and the momentum spread of the beam were also recorded under the same conditions. The smallest vertical rms emittance measured at low intensity is 4 pm at a beam energy of 1.3 GeV, which corresponds to the normalized emittance of 1.0x1.0(-8) m. It increases by a factor of 1.5 for a bunch intensity of 10(10) electrons. The measured data agreed to the calculation of intrabeam scattering within much better than a factor of 2.

Journal Article↗
PubMed2004

Anatomical variations of occipital bone impressions for dural venous sinuses around the torcular Herophili, with special reference to the consideration of clinical significance.

Venous blood flow through the cerebral dural sinus is variable and clinically significant. It has been investigated by cadaver dissection or radiology; however, we thought that osteology might be informative. A total of 160 dried skulls were macroscopically examined for impressions on the inner surface of the occipital bone in order to interpret the sinus flow around the torcular Herophili. The continuity between the grooves for the superior sagittal sinus (SSS) and the transverse sinuses was categorized into four types. Confluence type was noted in 56 specimens (35%), in which SSS drained into a common pool of venous sinuses. Bifurcation type was noted in 22 cases (14%), in which SSS was divided to drain into the bilateral transverse sinuses. Right dominant type was the most frequent one with 66 cases (41%), in which SSS drained only into the right transverse sinus. Left dominant type was the least frequent one with 16 cases (10%), in which SSS drained to the left, in a mirror image to the right dominant type. Clinical significance is discussed with our preliminary trial for the optimization of the inner skull surface and venous flow using computed tomography and magnetic resonance imaging, and demonstration of cerebrovascular disease.

Adult↗
PubMed2004

Detection and localization of periodontopathic bacteria in abdominal aortic aneurysms.

OBJECTIVES: We examined a possible link between periodontal disease and abdominal aortic aneurysm (AAA) by studying resected aneurysmal specimens from AAA patients for the presence of periodontopathic bacteria. DESIGN: Prospective case control study. MATERIAL AND METHODS: Thirty-two AAA patients were enrolled in the study. Periodontitis was classified according to the probing depth of periodontal pocket. Thirty-two aneurysmal walls, 16 mural thrombi, 5 atherosclerotic occlusive aorta and 5 control arterial tissue, were examined for 7 periodontal bacteria using polymerase chain reaction (PCR) method. The localization of the bacteria in the aneurysmal/atherosclerotic wall was determined by thromboendarterectomy. RESULTS: All patients had periodontal disease, and most cases were severe. PCR examination of the aneurysmal specimens showed that 86% were positive for periodontal bacterial DNA. No bacteria were detected in the control specimens. The bacteria were found in both the intimal/medial layer and the adventitial layer of the aneurysmal wall but only in intimal/medial layer of the atherosclerotic occlusive aorta. CONCLUSION: Periodontopathic bacteria were present in a high percentage of specimens of diseased arteries from AAA patients and were found throughout the whole aneurysmal wall. These bacteria may play a role in the development of AAAs and/or contribute to weakening the aneurysmal wall.

Aged↗
PubMed2004

Metal contents in Porites corals: Anthropogenic input of river run-off into a coral reef from an urbanized area, Okinawa.

In order to monitor pollutants from urban areas to coral reefs, metal contents in Porites coral samples collected from the Hija River mouth and at nearby sites from the estuary were analyzed. The corals were cleaned by oxidative and reductive treatments to effectively eliminate detritus and organic materials. Metal-to-calcium (Me/Ca) ratios in the samples were determined by ICP-MS. Filtered samples of river water were also measured similarly for metal concentrations. The extent of anthropogenic contribution by riverine input was assessed by comparing the Me/Ca values in corals to those of Rukan-sho, an unpolluted coral reef. High riverine inputs of Mn, Cd, Zn and Ag were observed from Me/Ca values in the coral samples. Manganese in the coral samples showed strong dependence on salinity, varying inversely to the distance from terrestrial sources. Considering a lead background of 25.0 nmol/mol measured in the Rukan-sho corals, Pb/Ca in corals of the Hija River estuary that are two and three times higher may indicate lead enrichment in the river mouth. Because Pb is only moderately high in the Hija River water compared to its concentration in surface seawater, lead may have accumulated in the estuarine water and sediments, resulting in an elevated concentration of lead available for coral uptake.

Animals↗
PubMed2004

Transpupillary thermotherapy for treatment of exudative age-related macular degeneration in Japanese patients.

PURPOSE: To report the therapeutic outcome of transpupillary thermotherapy (TTT) for subfoveal choroidal neovascularizarion (CNV) in brown retina using a diode-laser with the setting of lower energy level compared to the previous studies on light-pigmented Caucasian patients. METHODS: A total of 19 subfoveal CNVs in 18 patients were treated with TTT. The power of diode-laser was set 160 mW for 1.2 mm beam, 270 mW for 2.0 mm beam, and 400 mW for 3.0 mm beam, and the laser was delivered for 1 min through a slit-lamp mounted-delivery system. Patients were followed up for a mean of 8.8 months (4-12 months). Visual acuity and the fundus change as judged by funduscopic examination and simultaneous fluorescein and indocyanine green angiography were evaluated. Visual acuity was measured by a Japanese standard Landolt visual acuity chart and converted to logarithm of the minimal angle resolution (log MAR) visual acuity for statistical analysis. Improvement or decline in vision was defined as change of more than 0.2 in log MAR visual acuity. RESULTS: In eyes with minimally classic or occult only CNV, visual acuity improved in two eyes (18%) stabilized in seven eyes (64%) and worsened in two eyes (18%). In eyes with predominantly classic CNV, visual acuity improved in two eyes (25%), stabilized in four eyes (50%) and worsened in two eyes (25%). In all, 15 (84%) eyes of all studied subjects had improvement in exudation. Two (11%) and one (5%) eye(s) were noted to have a significant post-treatment haemorrhage and retinal pigment epithelial tear, respectively. CONCLUSION: In patients with brown retinal colour, the treatment outcome of TTT was comparable to that of light-pigmented Caucasian patients with approximately half the laser power energy. Further randomized control studies are warranted.

Aged↗
PubMed2004

Sexual activities and social relationships of people with HIV in Japan.

Sixty-one Japanese with sexually transmitted HIV were investigated to clarify the state of, and difficulties in, their sexual activities and social relationships. The study revealed the following difficulties in social relationships due to HIV infection. Thirty-one per cent had experienced discrimination or breach of confidentiality. Self-restriction due to anxiety over discrimination was observed in approximately 90%, and the self-restriction score tended to be higher in those who were not employed, those with economic problems, those who were in a relatively poor state of health, those who had developed AIDS and those who had previously experienced discrimination or breach of confidentiality. The experience of discrimination or breach of confidentiality, and the experience of receiving negative support tended to increase as the respondents had a wider emotional support network. About 60% were dissatisfied with their sex lives, and the degree of satisfaction was significantly lower in those who had fewer sexual contacts and those who had a suppressive attitude toward sexual contacts. A low degree of satisfaction with sex life was found to be an important factor that escalates the level of depression or anxiety.

Adaptation, Psychological↗
PubMed2004

Expression of RUNX3 protein in human gastric mucosa, intestinal metaplasia and carcinoma.

BACKGROUND: Human runt-related transcription factor gene 3 (RUNX3) is considered as a possible candidate of tumour suppressor gene in human gastric carcinoma. MATERIALS AND METHODS: To investigate the RUNX3 protein expression in human gastric mucosa and carcinoma, we generated a polyclonal antibody, AS251, which recognized amino acid sequences from 251 to 266 of human RUNX3. The AS251 antibody was immunoreactive with only RUNX3 protein, but not with RUNX1 and RUNX2. The AS251-antibody was available for Western blotting and immunohistochemistry using paraffin-embedded specimens. RESULTS: Western-blot analysis revealed that three (MKN-1, -7 and -45) of six human gastric carcinoma cell lines variably expressed RUNX3 protein, consistent with the expression pattern of RUNX3 mRNA reported previously by Li et al. (Cell 2002;109:113-24). Immunohistochemistry disclosed RUNX3 protein in most chief cells and a few gastrin-containing G cells in normal mucosa, but not in intestinal metaplasia and carcinoma cells. CONCLUSIONS: These data suggest that RUNX3 may play a physiologic role in chief cells and G cells in gastric mucosa, and that suppression of RUNX3 expression in intestinal metaplasia and carcinoma of human stomach may be implicated in gastric carcinogenesis.

Amino Acid Sequence↗
PubMed2004

Absence of association between the MCP-1 gene polymorphism and histological phenotype of lupus nephritis.

Lupus nephritis presents two polar histological patterns, diffuse proliferative glomerulonephritis (DPGN) and membranous glomerulonephritis (MGN). In the kidney tissue of DPGN, numerous mononuclear cells were seen in the interstitium and glomeruli; on the other hand in MGN, infiltrating cells were less frequent. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemoattractant for monocytes, T-cells, and natural killer cells. In this study we assessed the significance of the MCP-1 gene in determination of the histological phenotype in lupus nephritis. There was no association between the risk of DPGN and the MCP-1 gene genotype.

Adolescent↗
PubMed2004

[Pulmonary thromboendarterectomy for an elderly patient].

We describe a case of successful pulmonary thromboendarterectomy for an elderly patient. A 75-year-old female suffered from severe dyspnea in spite of administration of pulmonary vascular dilators and anticoagulants. Her pulmonary vascular resistance was 545 dyn x sec x cm(-5) and, her pulmonary angiogram and perfusion scan revealed that almost all branches of her right pulmonary artery were occluded. Pulmonary thromboendarterectomy was performed under cardiopulmonary bypass. A videoscope was employed to see inside of the pulmonary artery. Flexible aspirator chip was used to peed abnormal intima easily. A non-invasive intracranial oxygen saturation monitor was used for secure circulatory arrest. The duration of cardiopulmonary bypass was 101 minutes and minimum body temperature was 24.5 degrees C. Her symptoms improved markedly after operation, and she went back to the ordinary life. Pulmonary thromboendarterectomy was useful even for elderly patients under some modifications of the operative procedures.

Aged↗
PubMed2004

[Pulmonary embolectomy followed by lobectomy to treat for massive endobronchial bleeding; report of a case].

We describe a case of successful pulmonary embolectomy that required lobectomy to treat for endobronchial bleeding. Sixty-nine-year-old female got into shock required CPR during rehabilitation after replacement of femur head. Her enhanced computed tomography (CT) showed massive embolism in pulmonary artery. Emergency embolectomy was performed under cardiopulmonary bypass (CPB). A videoscope was employed to see inside the pulmonary artery. At the end of the CPB, endobronchial bleeding occurred. The right bronchus was occluded by balloon and CPB was weaned. The right lower lobectomy was done on the next day. She had got pyothorax by methicillin-resistant Staphylococcus aureus (MRSA), and has recovered after intravenous administration of antibiotics and continuous wash out of pleural space by saline containing 0.02% povidon-iodine. Postoperative scan showed no defects of blood flow and ventilation except resected lobe.

Aged↗
PubMed2003

A screening system for antioxidants using thioredoxin-deficient yeast: discovery of thermostable antioxidant activity from Agaricus blazei Murill.

Previously, we found that cytosolic thioredoxin is a negative regulator for an oxidative stress responsive transcription factor, Yap1p (yeast AP-1-like transcription factor), i.e., this transcription factor is constitutively concentrated in the nucleus in the thioredoxin-deficient mutant ( trx1delta trx2delta) due to an impairment of the reactive oxygen species-scavenging activity of this mutant [Izawa et al. (1999) J Biol Chem 274:28459-28465]. Based on these findings, we developed a screening method to discover substances that show antioxidant activity. With this method, antioxidant activity was evaluated by monitoring the subcellular localization of Yap1p. Since Yap1p is oxidized and accumulates in the nucleus in trx1delta trx2Delta cells, it is easy to identify antioxidant activity by observing the localization of green fluorescent protein (GFP)-tagged Yap1p. If exogenous substances taken in by trx1delta trx2Delta cells were able to function as antioxidants to reduce the oxidized form of Yap1p, GFP1-Yap1p would diffuse into the cytoplasm. We used this system to screen for antioxidant activity in mushrooms, and found that the edible mushroom Agaricus blazei Murill is an excellent source of antioxidants.

Agaricus↗
PubMed2003

Increased TUNEL positive cells in human alcoholic brains.

Alcohol-sensitive neuronal cell loss, which has been reported in the superior frontal cortex and hippocampus, may underlie the pathogenesis of subsequent cognitive deficits. In the present study, we have used the TUNEL labeling to detect the DNA damage in human alcoholic brains. Seven out of eleven alcoholics exhibited TUNEL-positive cells in both superior frontal cortex and hippocampus, which were co-localized with GFAP immunoreactivity. In contrast, almost no positive cells were detected in the non-alcoholic controls. None of the TUNEL-positive cells showed any typical morphological features of apoptosis or necrosis. TUNEL-positive cells observed in the present study may indicate DNA damage induced by ethanol-related overproduction of reactive oxygen species.

Adult↗