Biomedical subjects

Y Fujii

Publications and source records attributed to Y Fujii.

At least 271 records · Page 15Linked to original sources

PubMed1999

Perceptual processing of stereopsis in humans: high-field (3.0-tesla) functional MRI study.

Cortical activation associated with stereopsis was studied in eight right-handed neurosurgeons professionally trained in stereoscopic vision. The activation map associated with viewing three-dimensional images, as contrasted to viewing the corresponding two-dimensional images of identical contents (images of MR angiography), showed consistent activation in the cortex adjacent to the intraparietal sulcus. The study further demonstrated a dominant role of the right hemisphere in perceptual processing of stereopsis in humans.

Adult↗

PubMed1999

Double-layered membrane vesicles released from mammalian cells infected with Sendai virus expressing the matrix protein of vesicular stomatitis virus.

The matrix (M) protein of vesicular stomatitis virus (VSV) was reported to form vesicles on the cell surface and subsequently to be released into the cultured medium when expressed from cDNA by virus vectors. To further investigate VSV M activity, we generated a recombinant Sendai virus (SeV) expressing the VSV M protein (SeV-M(VSV)). When cells were infected with SeV-M(VSV), VSV M was found abundantly in the culture medium. Electron microscopy demonstrated the budding of two-membraned vesicles (>/= 0.8 microm in diameter) from the infected cells. The outer membrane of the vesicle was derived from the plasma membrane and the inner one possibly derived from the membrane of an intracellular vesicle. Immuno-gold labeling showed that VSV M was exclusively located in a double-layered region. The released membranes were divided into three parts: the VSV M vesicles with SeV F and HN glycoproteins, SeV particles, and vesicles associated with the cytosolic components. The last abundantly contained phosphorylated SeV matrix (M) protein, which is not released in a usual SeV infection. Furthermore the VSV M protein expressed without using a virus vector was efficiently released into the culture medium. These results suggest that the VSV M protein has a budding activity per se and that SeV proteins are passively involved in the release of VSV M.

Animals↗

PubMed1999

Crystal structure of an IRF-DNA complex reveals novel DNA recognition and cooperative binding to a tandem repeat of core sequences.

There has been growing interest in the role of the IRF (interferon regulatory factor) family of transcription factors in the regulation of immune responses, cytokine signaling, and oncogenesis. These members are characterized by their well-conserved DNA binding domains at the N-terminal regions. Here we report the 2.2 A resolution crystal structure of the DNA binding domain of one such family member, IRF-2, bound to DNA. The structure reveals its recognition sequence, AANNGAAA (here, recognized bases are underlined and in bold, and N indicates any base), and its cooperative binding to a tandem repeat of the GAAA core sequence induced by DNA structure distortions. These facts explain well the diverse binding properties of the IRF family members, which bind to both single and tandemly repeated sequences. Furthermore, we also identified the 'helix-hairpin-strand motif' at the C terminus of the recognition helix as a metal binding site that is commonly found in certain classes of DNA-interactive proteins. Our results provide new insights into the structure and function of this family of transcription factors.

Amino Acid Sequence↗

PubMed1999

Effects of histamine on MK-801-induced memory deficits in radial maze performance in rats.

The effects of histamine on the spatial memory deficits induced by MK-801 were investigated using the eight-arm radial maze paradigm in rats. Intracerebroventricular (i.c.v.) injection of histamine or thioperamide, and intraperitoneal (i.p.) injection of histidine improved the spatial memory deficits induced by MK-801. Similar results were obtained with 2-thiazolylethylamine. In contrast, 4-methylhistamine showed no significant effect. Based on these observations, it seems likely that the protective effect of histamine on MK-801-induced spatial memory deficit is mediated by H(1)-receptors.

Analysis of Variance↗

PubMed1999

Hemolysin of Aeromonas sobria stimulates production of cyclic AMP by cultured cells.

Hemolysin of Aeromonas sobria possesses both cytotoxic activity against mammalian cells and enterotoxic activity. Histopathological examination revealed that hemolysin causes diarrhea without damaging the intestinal epithelial cells. And the fluid accumulated in the mouse intestinal loop by the action of the hemolysin is watery. These observations indicated that the enterotoxic activity of hemolysin is not dependent on its cytotoxic activity. To clarify the mechanism of the enterotoxic action of hemolysin, we examined cyclic nucleotide levels in cultured cells exposed to this toxin. These results showed that hemolysin stimulates the production of cyclic AMP in cultured cells and the cyclic AMPs thus produced emerge in the milieu of cells.

Aeromonas↗

PubMed1999

Nitric oxide production by bronchoalveolar cells during allograft rejection in the rat.

BACKGROUND: We reported the increased nitric oxide (NO) level in exhaled air of rat lung transplant recipients during acute rejection (AR). The aim of this study was to determine the site and level of NO production in the rejected graft. METHODS: Rat lung transplantation was performed in isografts and allografts. RESULTS: In isografts, no AR and no significant increase in NO production was identified. In allografts, grades I-II of AR was seen on postoperative day (POD) 3 and grade III on POD 5. NO produced by BAL cells increased on both POD 3 (11.8+/-2.0 parts per billion [ppb]) and POD 5 (115.3+/-66.9 ppb). There was a highly significant correlation between the level of NO and the severity of AR (p=0.862, P<0.005). BAL cells from allografts expressed iNOS mRNA. Among them, macrophages, lymphocytes and neutrophils were immunostained for iNOS. CONCLUSION: NO produced by BAL cells was detected in the early stages of rejection. Therefore, it may serve as a sensitive indicator of AR in lung transplantation.

Animals↗

PubMed1999

The oxidized forms of dATP are substrates for the human MutT homologue, the hMTH1 protein.

The possibility that Escherichia coli MutT and human MTH1 (hMTH1) hydrolyze oxidized DNA precursors other than 8-hydroxy-dGTP (8-OH-dGTP) was investigated. We report here that hMTH1 hydrolyzed 2-hydroxy-dATP (2-OH-dATP) and 8-hydroxy-dATP (8-OH-dATP), oxidized forms of dATP, but not (R)-8,5'-cyclo-dATP, 5-hydroxy-dCTP, and 5-formyl-dUTP. The kinetic parameters indicated that 2-OH-dATP was hydrolyzed more efficiently and with higher affinity than 8-OH-dGTP. 8-OH-dATP was hydrolyzed as efficiently as 8-OH-dGTP. The preferential hydrolysis of 2-OH-dATP over 8-OH-dGTP was observed at all of the pH values tested (pH 7.2 to pH 8.8). In particular, a 5-fold difference in the hydrolysis efficiencies for 2-OH-dATP over 8-OH-dGTP was found at pH 7.2. However, E. coli MutT had no hydrolysis activity for either 2-OH-dATP or 8-OH-dATP. Thus, E. coli MutT is an imperfect counterpart for hMTH1. Furthermore, we found that 2-hydroxy-dADP and 8-hydroxy-dGDP competitively inhibited both the 2-OH-dATP hydrolase and 8-OH-dGTP hydrolase activities of hMTH1. The inhibitory effects of 2-hydroxy-dADP were 3-fold stronger than those of 8-hydroxy-dGDP. These results suggest that the three damaged nucleotides share the same recognition site of hMTH1 and that it is a more important sanitization enzyme than expected thus far.

Bacterial Proteins↗

PubMed1999

Decreased expression of myotonic dystrophy protein kinase and disorganization of sarcoplasmic reticulum in skeletal muscle of myotonic dystrophy.

Pathological expression of myotonic'dystrophy protein kinase (DMPK) in skeletal muscle of myotonic dystrophy (DM) was studied by Western blot analysis, immunohistochemistry, and immunoelectron microscopy of DMPK. Western blot analysis showed that DMPK protein in DM skeletal muscles dramatically decreased. DMPK-positive muscle fibers showed typical DM pathological changes such as type I atrophy, central nuclei, nuclear chains, and sarcoplasmic masses. In degenerated DMPK-positive muscle fibers, cross-striated bands disappeared, and irregular granular DMPK-positive materials appeared in sarcoplasm. By immunoelectron microscopy, DMPK was localized in the terminal cisternae of the sarcoplasmic reticulum (SR) in DM muscle. Swollen DMPK-positive SRs were detected between well preserved myofibrils in the early stage of DM muscle degeneration, and degenerated intramembranous structures with DMPK and an accumulation of mitochondria were observed between disorganized myofibrils in degenerated DM muscle. We concluded that SR is the primary site of the degeneration of DM skeletal muscle and that the decreased DMPK might cause dysregulation of intracellular calcium metabolism, which is followed by DM muscle degeneration.

Adenosine Triphosphatases↗

PubMed1999

cDNA cloning, expression, and mutagenesis study of liver-type prostaglandin F synthase.

Prostaglandin (PG) F synthase catalyzes the reduction of PGD2 to 9alpha,11beta-PGF2 and that of PGH2 to PGF2alpha on the same molecule. PGF synthase has at least two isoforms, the lung-type enzyme (Km value of 120 microM for PGD2 (Watanabe, K., Yoshida, R., Shimizu, T., and Hayaishi, O. (1985) J. Biol. Chem. 260, 7035-7041) and the liver-type one (Km value of 10 microM for PGD2 (Chen, L. -Y., Watanabe, K., and Hayaishi, O. (1992) Arch. Biochem. Biophys. 296, 17-26)). The liver-type enzyme was presently found to consist of a 969-base pair open reading frame coding for a 323-amino acid polypeptide with a Mr of 36,742. Sequence analysis indicated that the bovine liver PGF synthase had 87, 79, 77, and 76% identity with the bovine lung PGF synthase and human liver dihydrodiol dehydrogenase (DD) isozymes DD1, DD2, and DD4, respectively. Moreover, the amino acid sequence of the liver-type PGF synthase was identical with that of bovine liver DD3. The liver-type PGF synthase was expressed in COS-7 cells, and its recombinant enzyme had almost the same properties as the native enzyme. Furthermore, to investigate the nature of catalysis and/or substrate binding of PGF synthase, we constructed and characterized various mutant enzymes as follows: R27E, R91Q, H170C, R223L, K225S, S301R, and N306Y. Although the reductase activities toward PGH2 and phenanthrenequinone (PQ) of almost all mutants were not inactivated, the Km values of R27E, R91Q, H170C, R223L, and N306Y for PGD2 were increased from 15 to 110, 145, 75, 180, and 100 microM, respectively, indicating that Arg27, Arg91, His170, Arg223, and Asn306 are essential to give a low Km value for PGD2 of the liver-type PGF synthase and that these amino acid residues serve in the binding of PGD2. Moreover, the R223L mutant among these seven mutants especially has a profound effect on kcat for PGD2 reduction. The Km values of R223L, K225S, and S301R for PQ were about 2-10-fold lower than the wild-type value, indicating that the amino acid residues at 223, 225 and 301 serve in the binding of PQ to the enzyme. On the other hand, the Km value of H170C for PGH2 was 8-fold lower than that of the wild type, indicating that the amino acid residue at 170 is related to the binding of PGH2 to the enzyme and that Cys170 confer high affinity for PGH2. Additionally, the 5-fold increase in kcat/Km value of the N306Y mutant for PGH2 compared with the wild-type value suggests that the amino acid at 306 plays an important role in catalytic efficiency for PGH2.

Amino Acid Sequence↗

PubMed1999

Intestinal energy metabolism during ischemia and reperfusion.

BACKGROUND: In order to evaluate acute ischemic damage in the small intestine induced by superior mesenteric artery occlusion (SMAO) and subsequent reperfusion, changes in ATP, ADP, and AMP were measured by high-performance liquid chromatography, and changes in tissue blood flow were measured (from the serosal surface) by the laser doppler flow meter in a rat model. MATERIALS AND METHODS: The superior mesenteric artery of the rat was occluded for 30, 60, 90, and 120 min and then reopened. Core temperature was maintained carefully at 37 +/- 0.3 degrees C. RESULTS: All rats that underwent 90 and 120 min of SMAO died within 2 days, but those with 30 and 60 min of SMAO survived. ATP (10.39 +/- 0.90 micromol/g dry weight), ADP (3.34 +/- 0.33), and total adenine nucleotides (TAN; 14.08 +/- 0. 86) decreased with longer SMAO times. After 30 and 60 min of SMAO followed by reperfusion, recoveries of ATP and TAN were relatively good and ADP levels remained fairly steady, but little or no recovery of these levels was observed after 90 and 120 min of SMAO followed by reperfusion. There were linear correlations between the levels of ATP and TAN after 30 min of reperfusion and the time of SMAO. Tissue blood flow levels were constant during SMAO. After reperfusion, those levels were recovered along with the SMAO periods. But recovery rates compared with control values were not related with those of ATP. CONCLUSIONs. ATP and TAN levels, particularly at 30 min after reperfusion, seemed to be in good agreement with the tissue damage and the viability of the small intestine. We propose that the measurement of these levels may be useful for the evaluation of intestinal damage and viability.

Adenosine Diphosphate↗

PubMed1999

Flow cytometric study of lymphocytes associated with thymoma and other thymic tumors.

BACKGROUND: A large number of immature T lymphocytes in thymoma may reflect the biological function of the neoplastic epithelial cells. However, to confirm that this lymphocyte-inducing activity is unique to thymoma, lymphocytes associated with other thymic tumors need to be studied. MATERIALS AND METHODS: We used flow cytometry to study lymphocytes recovered from various thymic tumors (65 thymomas, 24 with myasthenia gravis; 5 thymic cancers; 5 germ cell tumors including 3 needle biopsy samples; and 2 other tumors) and results were analyzed in reference to those from 36 normal thymuses. RESULTS: The frequency of CD4(+)CD8(+) (DP) thymocytes in the normal thymus declined with age (0.9-94%, r = -0.83, P < 0.001) reflecting the physiological involution. Association of lymphocytes with this DP phenotype was unique to thymoma: 61 of 65 thymomas but none of the other thymic tumors had more than 3% DP cells (frequency of DP cells; thymoma without MG, 59.5 +/- 31.4%; thymoma with MG, 59.4 +/- 22.1%; and other thymic tumors, 0.8 +/- 1.0; mean +/- SD). All the thymic tumors associated with myasthenia gravis were thymomas and had more than 18% DP cells. CONCLUSION: The presence of DP cells in thymomas but not in other tumors suggests that DP cells are induced by the epithelial cells of thymoma. This characteristic may help diagnose thymic tumors; the presence of more than 3% DP cells suggests a thymoma. Also, association of myasthenia gravis suggests a thymoma.

Adult↗

PubMed1999

Identification and characterization of the Aeromonas sobria hemolysin glycoprotein receptor on intestine 407 cells.

Aeromonas sobria hemolysin is important in the pathogenesis of diarrhoea caused by this enteropathogenic bacterium. By immunoprecipitation analysis using hemolysin and anti-hemolysin antibody, a 66 kDa protein (p66) was identified as a receptor for A. sobria hemolysin on Intestine 407 cells. Treatment of p66 with N-glycosidase F reduced the apparent sized of p66 to 60 kDa on SDS-polyacrylamide gels. p66, released from Intestine 407 cells following incubation with phosphatidylinositol-specific phospholipase C (PI-PLC) treatment, bound A. sobria hemolysin. Thus treatment of Intestine 407 cells with PI-PLC resulted in the remarkable decrease of the sensitivity to A. sobria hemolysin. These results are consistent with the hypothesis that p66, the binding protein for A. sobria hemolysin, is a glycosylphosphatidylinositol-anchored glycoprotein expressed on the surface of Intestine 407 cells and probably plays a role as a receptor for A. sobria hemolysin on the intestinal cells.

Aeromonas↗

PubMed1999

Combined diltiazem and lidocaine reduces cardiovascular responses to tracheal extubation and anesthesia emergence in hypertensive patients.

PURPOSE: Hypertensive patients exhibit exaggerated cardiovascular responses to tracheal extubation. This study was undertaken to compare the efficacy of combined diltiazem and lidocaine with each drug alone in suppressing the hemodynamic changes during tracheal extubation. METHODS: Sixty hypertensive patients (ASA II), defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg (WHO), undergoing elective orthopedic surgery received, in a randomized, double-blind manner, 0.2 mg x kg(-1) diltiazem, 1.0 mg x kg(-1) lidocaine, or 0.2 mg x kg(-1) diltiazem plus 1.0 mg x kg(-1) lidocaine (n=20 of each) i.v. before tracheal extubation. Changes in heart rate (HR), mean arterial pressure (MAP) and rate-pressure product (RPP) were measured before and after tracheal extubation. RESULTS: Hemodynamic changes during tracheal extubation were less in patients receiving diltiazem plus lidocaine than in those receiving diltiazem or lidocaine as a sole medicine (RPP; 10322 +/- 1674 (combined) vs 11532 +/- 1802 (diltiazem), 15388 +/- 2050 (lidocaine), mean +/- SD, P < 0.05). CONCLUSION: Combined diltiazem and lidocaine is more effective prophylaxis than diltiazem or lidocaine alone for attenuating the cardiovascular responses to tracheal extubation and emergence from anesthesia in hypertensive patients.

Aged↗

PubMed1999

Ramosetron vs granisetron for the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy.

PURPOSE: To compare the efficacy of ramosetron with granisetron for the prevention of postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy. METHODS: In a randomized, double-blind study, 80 female inpatients received 3 mg granisetron or 0.3 mg ramosetron i.v. (n=40 of each) at the completion of surgery The standardized anesthetic included isoflurane and nitrous oxide in oxygen. RESULTS: Complete response, defined as no PONV, during the first 24 hr (0-24 hr) after anesthesia was 85% with granisetron and 93% with ramosetron, respectively (P=0.241); the corresponding incidence during the next 24 hr (24-48 hr) after anesthesia was 63% and 90% (P=0.004). No clinically important adverse events due to the study drug were observed in any of the groups. CONCLUSION: Ramosetron was more effective than granisetron for prevention of PONV during 0-48 hr after anesthesia for laparoscopic cholecystectomy.

Adult↗

PubMed1999

Landiolol decreases a dysrhythmogenic dose of epinephrine in dogs during halothane anesthesia.

PURPOSE: To examine the effect of landiolol (ONO-1101), a new ultra-short acting and highly selective beta blocker, on epinephrine-induced ventricular arrhythmias in halothane-anesthetized dogs. METHODS: We administered five different doses (0, 0.1, 0.5, 1.0, 10 microg x kg(-1) x min(-1)) landiolol and determined the dysrhythmogenic dose of epinephrine (DDE), defined as the smallest dose producing four or more PVCs within 15 sec, at each dose of landiolol and after cessation of infusion. RESULTS: The control value of DDE during 1.3 MAC halothane anesthesia was 1.26 +/- 0.44 (mean +/- SD) microg x kg(-1) x min(-1) and the corresponding plasma concentration of epinephrine (PCE) was 12.2 +/- 8.3 ng x ml(-1). Concomitant administration of 10 microg x kg(-1) x min(-1) landiolol increased DDE and corresponding PCE (P < 0.05). At 30 min after cessation of landiolol infusion, DDE and corresponding PCE returned to the control values. CONCLUSIONS: Landiolol, at a dose of 10 microg x kg(-1) x min(-1), has an antiarrhythmic effect on epinephrine-induced ventricular arrhythmias in dogs during anesthesia with halothane.

Adrenergic beta-Agonists↗

PubMed1999

Aortic dissection in an elderly patient with atrial septal defect.

We report a case of acute aortic dissection that occurred in the late course of surgically untreated atrial septal defect. A 60-year-old man with acute aortic dissection and atrial septal defect was operated on successfully, and we discuss the causal relationship between these two unusual conditions.

Aortic Dissection↗

PubMed1999

Tacrolimus versus cyclosporin A: a comparative study on rat renal allograft survival.

Although tacrolimus has been studied in a wide variety of experimental animal models, we are the first group to systematically study the effect of tacrolimus on rat renal allograft survival, as primary therapy and as anti-rejection therapy, in comparison with cyclosporin A (CyA). Renal grafts were transplanted from BN to LEW rats. Tacrolimus and CyA were administrated orally from day 0 for 50 days as primary therapy after grafting. Allografts were rejected after a median survival time (MST) of 8 days. Both tacrolimus und CyA significantly prolonged renal allograft survival, in a dose-dependent manner compared with the allograft controls. The most effective dose was 3.2 mg/kg, per day for tacrolimus, and 10 mg/kg per day for CyA. There was no significant difference in renal function between the group treated with the most effective dose of tacrolimus and the CyA-treated group. The percentage of detectable serum IL-2 level was 45% in the allograft control group, but was undetectable in groups treated with the most effective dose of tacrolimus or CyA at days 3 and 6 after grafting. On the other hand, no side effects were noted in recipient rats by daily inspection, body weight change, and histological studies, although minimal tubular vacuolation was encountered in the group treated with CyA 32 mg/kg per day. In addition, the most effective doses of tacrolimus and CyA were studied as anti-rejection therapy. All of the 5 recipients treated with tacrolimus from days 2-14, and 3 of the 5 treated from days 4-16 after grafting, survived for more than 50 days. However, the MST was 19 days for recipients treated with CyA from days 2-14, and 13 days for those treated from days 4-16 after grafting. In summary, tacrolimus as primary therapy induced rat renal allograft survival with renal function and side effects comparable with those of CyA. Interestingly, when both agents were used as anti-rejection therapy, tacrolimus, but not CyA, could significantly overcome ongoing renal allograft rejection in the rat.

Administration, Oral↗

PubMed1999

Measurement of forearm bone in children by peripheral computed tomography.

By means of peripheral computed tomography (pQCT), adult cortical bone density and volume was shown to be under a fixed rectilinear relationship regardless of age, sex, and presence or absence of osteoporosis. In children, however, the density-volume regression line followed a clearly different slope from that for adults (P < 0. 001), indicating a difference in property and composition of the cortical bone between growing bone of children and grown-up bone of adults. Although both relative cortical volume and density increased with age in both boys and girls, no significant increase of trabecular bone was noted in either during the growth period. When the same technique was applied to the bone of rats known to continue growing with indefinite modeling without remodeling, the regression line between cortical bone density and volume was different from that of adult humans and similar to that of growing human children. Growing bone in a constant process of modeling and mineralization thus seems to have cortical bone possibly with less complete mineralization somewhat different from those of grown-up bone only undergoing remodeling. Selective cortical bone measurement by pQCT appears to be useful in characterizing the unique properties of the cortex of the growing bone.

Adolescent↗