Search PubMed⌕ Search

Biomedical subjects

Y Koga

Publications and source records attributed to Y Koga.

At least 37 records · Page 2Linked to original sources
PubMed2001

Inducible nitric oxide synthase deficiency does not affect the susceptibility of mice to atherosclerosis but increases collagen content in lesions.

BACKGROUND: Although endothelial nitric oxide synthase (NOS) is antiatherogenic, the role of inducible NOS (iNOS) in the development of atherosclerosis is not established. METHODS AND RESULTS: We compared the susceptibility of iNOS knockout (iNOS(-/-)) and wild-type (iNOS(+/+)) mice to the development of atherosclerosis induced by feeding an atherogenic diet for 15 weeks. Plasma lipid level, atherosclerotic lesion size, and cellular density in the lesions were all similar in the 2 strains (lesion size: iNOS(+/+) 285+/-73x10(3) microm(2), iNOS(-/-) 293+/-82x10(3) microm(2), n=10). iNOS mRNA was detected in the lesions of iNOS(+/+) but not iNOS(-/-) mice through RT-PCR. Immunohistochemically, iNOS(+/+) mice showed iNOS staining in macrophages and medial smooth muscle cells in the lesions. Nitrotyrosine staining showed a similar distribution, whereas it was absent in iNOS(-/-) mice. There was no apparent difference in the intensity or distribution of vascular cell adhesion molecule-1 staining in the lesions of the 2 strains. However, the lesions of iNOS(+/+) mice showed a markedly decreased extracellular collagen content compared with those of iNOS(-/-) mice CONCLUSIONS: iNOS induction does not affect the development of atherosclerosis in mice fed an atherogenic diet, but the resulting lesions show decreased levels of extracellular collagen and may be more fragile.

Animals↗
PubMed2001

Binding of small alcohols to a lipid bilayer membrane: does the partitioning coefficient express the net affinity?

The total vapor pressures at 26 degreesC of binary (water-alcohol) and ternary (water-alcohol-vesicle) systems were measured for six short chain alcohols. The vesicles were unilamellar dipalmitoyl phosphatidylcholine (DMPC). The data was used to evaluate the effect of vesicles on the chemical potential of alcohols expressed as the preferential binding parameter of the alcohol-lipid interaction, gamma23. This quantity is a thermodynamic (model-free) measure of the net strength of membrane-alcohol interactions. For the smaller investigated alcohols (methanol, ethanol and 1-propanol) gamma23 was negative. This is indicative of so-called preferential hydration, a condition where the affinity of the membrane for water is higher than the affinity for the alcohol. For the longer alcohols (1-butanol, 1-pentanol, 1-hexanol) gamma23 was positive and increasing with increasing chain length. This demonstrates preferential binding, i.e. enrichment of alcohol in the membrane and a concomitant depletion of the solute in the aqueous bulk. The measured values of gamma23 were compared to the number of alcohol-membrane contacts specified by partitioning coefficients from the literature. It was found that for the small alcohols the number of alcohol-membrane contacts is much larger than the number of preferentially bound solutes. This discrepancy, which is theoretically expected in cases of very weak binding, becomes less pronounced with increasing alcohol chain length, and when the partitioning coefficient exceeds approximately 3 on the molal scale (10(2) in mole fraction units) it vanishes. Based on this, relationships between structural and thermodynamic interpretations of membrane partitioning are discussed.

Alcohols↗
PubMed2001

Small molecular mass inhibitor of growth of MDCK cells derived from pig spinal cord.

We have discovered cell growth inhibitory activity in a salt extract of pig spinal cords. The growth inhibitory factor was purified by gel-filtration, ion-exchange and high performance liquid chromatography. Incubation of MDCK cells with the inhibitor arrested their locomotion within half an hour, suppressed their proliferation, and caused them to become round. The round cells that were still attached to the culture plate were alive. Upon removal of the inhibitor these cells flattened out and resumed locomotion and proliferation. The inhibitor was 100 times less effective on CHO-K1 cells. The reversible effects of the inhibitor on MDCK cells and its little effects on CHO-K1 cells indicate that the inhibitory activity is not due to a non-specific toxic mechanism. The inhibitor was both heat-stable and resistant to several chemical treatments, including proteases. Its behavior upon ion exchange chromatography suggested that it was positively charged at neutral pH, whilst its molecular mass was estimated to be 350 or larger by gel-filtration FPLC analysis. The inhibitory fraction reacted extensively with fluorescamine, suggesting that the inhibitory factor has amine groups, which are a possible candidate for its positive charges. Since spermine and spermidine, unlike the inhibitor in the present study, irreversibly inhibited the growth of the MDCK cells, the inhibitory activity in the present study is thus not due to contamination by these polyamines. Our experiments also support that the inhibitor is not a peptide.

Animals↗
PubMed2001

Cross-checking of nanoelectrospray ionization mass spectrometry and computer simulation for the evaluation of the interaction strength of non-covalently bound enkephalins in solution.

Nanoelectrospray ionization mass spectrometry (nanoESI-MS) and computer simulation were applied to the characterization of non-covalent interactions of [Leu5]-enkephalin (LE) and its optical isomers, [D-Tyr1, Leu5]-enkephalin (Y-LE), [D-Phe4, Leu5]-enkephalin (F-LE) and [D-Tyr1, D-Phe4, Leu5]-enkephalin (YF-LE). The dimer formation tendencies of the optical isomers of LE were evaluated by nanoESI-MS using quadruply deuterated LE (H2N-Tyr-(2,2-d2)Gly-(2,2-d2)Gly-Phe-Leu-COOH, d4-LE) as an internal standard. The relative interaction strengths of the optical isomers of LE were estimated to be Y-LE < F-LE < LE < YF-LE. Geometry optimization calculations were performed for interactions in vacuo and in water using a semi-empirical SCF method (PM3). The initial coordinate of the dimer structure of LE was taken from that obtained from single-crystalline x-ray diffraction analysis. Estimates of the interaction strengths of the dimer complexes were based on the heats of formation of a dimer complex (Hd) and the corresponding monomers (Hm) using the equation DeltaH = Hd - 2Hm. The values of DeltaH obtained from the calculations for interactions in water decreased in the order Y-LE > F-LE > LE > YF-LE. Since the smaller values of DeltaH correspond to stronger interactions between peptides, the results from computer simulations were qualitatively consistent with those obtained from the nanoESI experiments. The possibility of cross-checking these independent techniques was demonstrated using medium-sized molecules of biological importance. The agreement of the results from the two techniques suggested that nanoESI experiments, at least qualitatively, reflected the relative interaction strengths of non-covalently bound enkephalins in aqueous solution.

Computer Simulation↗
PubMed2001

Bone tunnel enlargement after anterior cruciate ligament reconstruction using hamstring tendons.

We retrospectively reviewed 87 anterior cruciate ligament reconstructions using autogenous hamstring tendons with the Endobutton technique to investigate the relationship between bone tunnel enlargement and clinical outcome and to identify factors that contribute to the enlargement. The clinical outcome was evaluated using the Lysholm score and KT-1000 arthrometer. The location of the femoral tunnel with respect to Blumensaat's line, the tibial tunnel with respect to the tibial plateau, and the angle between the femoral tunnel and Blumensaat's line (femoral tunnel angle) were measured. Bone tunnel enlargement was observed in 32 patients (37%). Enlargement occurred in 22 of the femoral tunnels and 26 of the tibial tunnels. Enlargement of both tunnels occurred in 16 knees. There was no statistical difference in Lysholm scores or KT-1000 arthrometer measurements between the enlarged group and the unenlarged group. The femoral tunnel was placed more anteriorly in the enlarged femoral tunnel group than in the unenlarged femoral tunnel group. The tibial tunnel was placed more anteriorly in the enlarged tibial tunnel group than in the unenlarged tibial tunnel group. The femoral tunnel angle was significantly smaller in the enlarged femoral tunnel group than in the femoral unenlarged group. Gender, patient age, intraoperative isometricity, and graft size were not significant factors. Bone tunnel enlargement was not correlated with the clinical outcome measures. We conclude that the main factor associated with tunnel enlargement are the locations and angles of the tunnels. The windshield-wiper motion of the graft may be enhanced by changing tension in the graft due to tunnel malposition. An acute femoral tunnel angle may increase the mechanical stress on the anterior margin of the femoral tunnel.

Adolescent↗
PubMed2001

Inter- and/or intra-organ distribution of mitochondrial C3303T or A3243G mutation in mitochondrial cytopathy.

Fatal infantile mitochondrial cytopathy associated with a C3303T mutation in the mitochondrial tRNA(Leu(UuR)) gene has been reported clinically, biochemically and genetically. Here we have analyzed the percentage of this mutation in various autopsied tissues, and also in single muscle fibers using a micromanupulator, to evaluate the correlation between the pathology and heteroplasmic condition using polymerase chain reaction/restriction fragment length polymorphism. A 5-month-old Japanese girl was admitted to our hospital showing generalized muscle weakness, hepatomegaly, and cardiomegaly with lactic acidosis, and died at 6 months of age. Skeletal muscle showed severe degenerating myopathy found to be full of ragged-red fibers (RRFs), an increased number of lipid droplets, and severe cytochrome c oxidase (COX) deficiency. Microscopically hepatocytes showed massive accumulation in lipid droplets, and the heart muscle showed a network pattern suggesting metabolic cardiomyopathy. The activities of respiratory chain enzyme complex I and complex IV in the skeletal muscle were significantly decreased to 23.4% and 5.0%, respectively, of the control value. The percentage of C3303T mutation in the patient tissues were variable, and ranged from 25% in the pancreas to 99% in the spinal cord. By single fiber analysis, the percentages of C3303T mutation in RRFs with COX negative (group 1; 42.4+/-7.0) and with COX positive (group 2; 58.2+/-5.8) were significantly higher than in non RRFs with normal COX staining (group 3; 10.7+/-6.3) (both P>0.001). Our patient showed a fatal infantile form of encephalopathy, myopathy and cardiomyopathy associated with widely distributed C3303T mutation in all of somatic cells.

DNA Mutational Analysis↗
PubMed2001

Effect of infraorbital nerve block under general anesthesia on consumption of isoflurane and postoperative pain in endoscopic endonasal maxillary sinus surgery.

PURPOSE: The efficacy of infraorbital nerve block in reducing isoflurane consumption and postoperative pain was evaluated in patients undergoing endoscopic endonasal maxillary sinus surgery (ESS) under general anesthesia. METHODS: Fifty patients were randomly allocated to either the block group (n =15) or the nonblock group (n = 25). After the establishment of general anesthesia with isoflurane, nitrous oxide, and oxygen, the patients received infraorbital nerve block with 1.0 ml of either 0.5% bupivacaine (block group) or normal saline (nonblock group) administered into the soft tissue in front of the infraorbital foramen. Systolic blood pressure during anesthesia and surgery was maintained at 85-90 mmHg by adjusting the inspiratory concentration of isoflurane, and its consumption was evaluated in both groups. Pain intensity at 15 min after the end of anesthesia was also evaluated on a five-point pain scale. RESULTS: The consumption of isoflurane under a fresh gas flow of 6 l.min(-1) was 17.3 +/- 6.5 ml.kg(-1).h(-1) (mean +/- SD) in the block group and 27.4 +/- 9.4 ml.kg(-1).h(-1) in the nonblock group during surgery ( P < 0.001). Nicardipine was required during surgery less frequently in the block group than in the nonblock group ( P < 0.01). Postoperative pain intensity was lower in the block group than in the nonblock group ( P < 0.01). CONCLUSION: General anesthesia combined with infraorbital nerve block is effective in reducing the consumption of isoflurane and postoperative pain intensity in ESS.

Clinical Trial↗
PubMed2001

Nitric oxide targets bronchiolar epithelial cells in murine cytomegalovirus-associated disease in lungs that are free of the virus.

At 4 weeks after intraperitoneal (i.p.) injection of 0.2LD50 (50% lethal dose) of murine cytomegalovirus (MCMV) in adult BALB/c mice, productive virus and the viral DNA were detected only in the salivary glands, but not in the lungs. A single i.p. injection of anti-CD3 mAb to these mice provoked pulmonary lesions, which included a thickening of the interstitium and peribronchiolar areas, accompanied with a cellular infiltration in those areas. As a result, half of the mice died. In a histochemical analysis with anti-nitrotyrosine polyclonal Ab, bronchiolar epithelial cells were stained with this Ab, thus demonstrating that peroxynitrite, which was biochemically derived from nitric oxide (NO), injured those cells. Similarly, when T cells of iNOS+/+ mice, which had been infected with MCMV 4 weeks before, were activated by a single injection of anti-CD3 mAb, 37.5% of the mice died. Nitrotyrosine was also detected in the bronchiolar epithelial cells in these mice. In contrast, none of MCMV-infected iNOS-/- mice died after the anti-CD3 injection. No pathological changes were noted in the histological findings of the lungs of those mice. An intranasal injection of bacterial superantigen, staphylococcal enterotoxin B (SEB), demonstrated the same histopathological changes in the lungs and mortality in BALB/c mice as those in mice i.p. injected with anti-CD3. Therefore, T-cell responsiveness to stimulation with anti-CD3 or a superantigen was presumably modified by MCMV infection. MCMV-associated pneumonitis in the present study was thus mediated not by a direct viral attack but by iNOS-derived NO, which can be induced by the cytokines from the T cells. In addition, it was demonstrated that the NO produced by the cytokine-mediated pathway targeted bronchiolar epithelial cells.

Animals↗
PubMed2001

Multiple osteochondroses of bilateral knee joints.

We experienced a patient with a combination of multiple osteochondroses: Blount's disease, bipartite patella, and Sinding-Larsen-Johansson disease in the left knee, and a combination of bipartite patella and Osgood-Schlatter disease in the right knee. The patient was a healthy, active 12-year-old boy with bilateral knee pain. He had been diagnosed with Blount's disease of the left tibia at 2 years of age, and had been treated with open wedge osteotomy. He was diagnosed with bilateral bipartite patellae at the age of 9 years, and was diagnosed with Osgood-Schlatter disease in the right knee and Sinding-Larsen-Johansson disease in the left knee at 10 years of age. The second growth spurt was observed during this period. At 11 years of age, he was diagnosed with an osteochondral fracture of the left lateral femoral condyle and was observed without surgery. This patient showed the sequential appearance of an ossification disorder, probably due to the abnormal response of enchondral ossification to mechanical stress. Overuse in this growth period may have played a role in the development of these osteochondroses. The osteochondral fracture was probably caused by a disruption at one of the weakest parts of the developing skeleton, between the ossification center and the overlying cartilage in the background of an ossification disorder.

Body Height↗
PubMed2001

Long-term results of non-operative treatment of anterior cruciate ligament injury.

We retrospectively reviewed the record of 89 patients with complete anterior cruciate ligament injury, documented by arthroscopic examination to investigate the long-term results in relation to the generation of osteoarthritis. The mean age of the patients was 34.9 years at follow-up and the mean duration of follow-up was 12.0 years. The mean Lysholm score was 89 points at follow-up. The mean Tegner activity score was 5.7 points before injury and 4.5 points at follow-up. Plain radiographs revealed 63% of osteoarthritis and 37% of which had joint space narrowing. The age of the patients, the level of sports activity, the history of meniscectomy, obesity and the osteoarthritis of the contralateral knee were found to be significant risk factors in osteoarthritis after anterior cruciate ligament injury. The most influential factor for osteoarthritis was considered meniscectomy, in combination with the risk factors of primary osteoarthritis. It should also be noted that modification of sports activity level was the most important factor for avoiding the combined injury of meniscus and osteoarthritis.

Adult↗
PubMed2001

Development of a three-dimensional jaw-tracking system implanted in the freely moving mouse.

A high-resolution mandibular tracking system was designed and tested in a freely moving mouse. A sensor unit, which consisted of four small magnetic sensors, was employed to trace small magnet movements in the three-dimensional space. After the sensor's output-to-displacement transformation equations were obtained from a multiple regression analysis of pre-experimental calibration data, the magnet and the sensors were transferred to the mouse, being kept at the same configuration as determined in the calibration system. In order to measure the three-dimensional jaw movements, the magnet was glued on the mandibular surface of the mouse and the sensor unit was implanted in the nasal bone. Jaw-movement trajectories were obtained as electrical signals from the sensors after being compensated by the output-to-displacement transformation equations of the sensors with a personal computer. This sensor system, applied to the freely moving mouse, could trace the jaw trajectories with an accuracy of better than 20 microm in three-dimensional space. Consequently, the typical pattern of the rhythmical jaw movements of the mouse during mastication was obtained. The mouse protruded the mandible to the most anterior position in the jaw-opening phase and retruded to it the most posterior position in the jaw-closing phase. This tracking system may also be applied to other small animals.

Animals↗
PubMed2001

In vivo measurement of the elastic modulus of the human periodontal ligament.

The present study was designated to determine the elastic properties of the periodontal ligament (PDL) in human subjects. A maxillary central incisor was experimentally translated so that stress or strain could be uniformly distributed in the PDL by applying a single force passing through the center of resistance. Displacements were measured under different magnitudes of load using a magnet-magnetic sensing system. From the load-displacement relations, Young's modulus of the PDL was calculated. The values determined were approximately 0.12 MPa under load ranging from 0 to 0.5 N, 0.25 MPa within the range of 0.5-1.0 N, 0.44 MPa under load 1.0-1.5 N, and between 0.69 and 0.96 MPa with 1.5-2.0 N. The values of Young's moduli increased almost exponentially with the increment of load due to a non-linear elasticity of the PDL.

Adult↗
PubMed2001

Transcription-mediated amplification is more useful in the follow-up of patients with chronic hepatitis B treated with lamivudine.

Changes in the HBV DNA level during the treatment of patients with chronic hepatitis B with lamivudine were investigated by the transcription-mediated amplification (TMA) assay. Twenty-four patients treated with lamivudine (males:female= 20:4, age: 44.0+/-9.0 years, chronic hepatitis: 14, cirrhosis: 7, cirrhosis with hepatocellular carcinoma: 3) were investigated. The dosage of lamivudine was 75 mg/day in 3, 100 mg/day in 8, and 150 mg/day in 13 patients, and the administration period was 48+/-16 weeks (24-79 weeks). Sixteen patients were HBe antigen-positive before treatment, and the HBV DNA level was 7.4+/-1.2 (4.0- more than 8.7) LGE/ml. The HBV DNA level was measured every 1-6 months by the TMA assay and the branched DNA signal amplification technology (b-DNA assay). Serum HBV DNA disappeared in all patients by the b-DNA during the treatment period, while six patients had persistent HBV DNA by the TMA. The time of HBV DNA disappearance by the TMA in 18 patients was 2-5 months after initiation of treatment. The disappearance rate of HBV DNA was 3/8 (38%) in patients whose HBV DNA level before treatment was 8.0 LGE/ml or higher, 7/8 (88%) in those with 7-7.9 LGE/ml, and 8/8 (100%) in those with 6.9 LGE/ml or lower, showing that disappearance of HBV DNA became difficult when the HBV DNA level before treatment was high (P<0.01). In six patients, the HBV DNA level disappeared once, then increased thereafter. The present findings suggested that these increases in the HBV DNA level were due to an increase of YMDD mutant in three of these six patients, and due to a decrease in the dosage in two patients. In treatment with lamivudine, the TMA assay is more useful for understanding the changes in the HBV DNA level than b-DNA assay.

Journal Article↗
PubMed2001

Pharmacodynamic effects and kinetic disposition of rabeprazole in relation to CYP2C19 genotypes.

BACKGROUND: S-mephenytoin 4'-hydroxylase (CYP2C19) catalyses the metabolism of rabeprazole to some extent. Based on the metabolic and pharmacokinetic differences among other proton pump inhibitors such as omeprazole, lansoprazole and pantoprazole, rabeprazole appears to be the least affected proton pump inhibitor by the CYP2C19-related genetic polymorphism. AIM: To determine whether the pharmacodynamic effects of rabeprazole on intragastric pH and serum gastrin levels, and its pharmacokinetics depend on the CYP2C19 genotype status. METHODS: Eighteen healthy subjects, whose CYP2C19 genotype status was previously determined, participated in the study. They consisted of six each of homozygous extensive metabolisers (homo EMs), heterozygous extensive metabolisers (hetero EMs), and poor metabolisers (PMs). Helicobacter pylori status was determined by serology. After a single oral dose of 10 mg or 20 mg rabeprazole or water only (baseline data), intragastric pH values were monitored for 24 h. Plasma levels of rabeprazole and serum gastrin were also measured for 24 h post-dose. RESULTS: Five homo EM, six hetero EM and four PM subjects were H. pylori-negative. After rabeprazole administration, significant differences in intragastric mean pH values, serum gastrin AUC(0-24) and plasma levels of rabeprazole were observed among the three different genotype groups. CONCLUSION: The pharmacodynamic effects of rabeprazole and its pharmacokinetics depend on the CYP2C19 genotype status.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Experimental evaluation of initial tooth displacement, center of resistance, and center of rotation under the influence of an orthodontic force.

The purpose of this study was to determine the location of the center of resistance and the center of rotation of the maxillary central incisors under the influence of a single simple force and to investigate related geometric parameters of the teeth and the surrounding periodontal tissues. By measuring the initial displacement of the central incisors with a magnetic sensing system, the location of the center of resistance and the centers of rotation associated with various forces were determined in 3 human subjects. The results show that the location of the center of resistance of the maxillary central incisor depends on the palatal bone level and is at approximately two-thirds of the palatal alveolar bone height, measured from the root apex. A greater moment-to-force ratio is needed for any controlled movement of the maxillary incisors during retraction in patients with reduced palatal alveolar bone height. This study suggests a method for estimating the location of the center of resistance of a tooth.

Alveolar Bone Loss↗
PubMed2001

The failure of oral tolerance induction is functionally coupled to the absence of T cells in Peyer's patches under germfree conditions.

Although intestinal bacterial flora has been thought to play a role in the induction of oral tolerance, the mechanism has yet to be elucidated. We therefore examined the bacterial flora-dependent acquisition of susceptibility to oral tolerance induction using a gnotobiotic murine model. Germ-free (GF) mice exhibited a significant shortage of T cells in the PPs in comparison to SPF mice. A recovery in the number of such T cells was accomplished in the gnotobiotic mice associated with Bifidobacterium infantis or Escherichia coli but not in the gnotobiotic mice with Clostridium perfringens or Staphylococcus aureus. To examine the susceptibility to oral tolerance induction, these mice were orally given ovalbumin (OVA) as a tolerogen and then injected i.p. with the Ag. The Ag-specific IgG1 in the serum remained at a low level in both SPF and those gnotobiotic mice groups containing a sufficient number of T cells in the PPs. However, no such unresponsiveness in the Ab response was observed in GF or the other gnotobiotic mice groups containing only a few T cells in the tissues. Adoptive cell transfer analysis clearly showed that a sufficient number of T cells in the PPs is required for the induction of oral tolerance. Furthermore, the reduced expression of SLC (secondary lymphoid-tissue chemokine), which is responsible for T-cell migration to lymphoid organs, was observed in the PPs of GF mice, resulting in a shortage of T cells in the tissues. However, the reduced expression of SLC was restored even in the GF mice after conventionalization, thus suggesting that the failure of oral tolerance induction is functionally coupled to the innate absence of T cells under the GF condition.

Administration, Oral↗
PubMed2001

Scanning electron microscopic observation of the architecture of collagen fibres in chicken M. iliotibialis lateralis.

1. The collagen architecture of M. iliotibialis lateralis in chicken was observed under the scanning electron microscope after muscle maceration in NaOH. 2. Immunohistochemical methods showed Type I and III collagens to be distributed over both perimysium and endomysium. 3. Thick perimysium around secondary myofibre fasciculi was composed of many large longitudinal collagen bundles and a few small circumferential bundles. In contrast, thin perimysium around primary myofibre fasciculi showed mainly circumferential bundles. 4. Endomysium had a honeycomb-like structure and consisted of a fine collagen mesh, its main fibre striation being circumferential. 5. It is suggested that functional demand differs between thick perimysium and thin endomysium.

Animals↗