Search PubMed⌕ Search

Biomedical subjects

N Shibata

Publications and source records attributed to N Shibata.

At least 91 records · Page 5Linked to original sources
PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 15). Two-week and 4-week administration study of methyl methanesulfonate (MMS).

This study was conducted to assess whether a 2-week treatment period is as effective as 4-week treatment for detection of drug-induced toxicity on the male rat reproductive organs using methyl methanesulfonate (MMS). A two-week study at dose levels of 20 or 40 mg/kg and a 4-week study with 20 mg/kg were conducted. The results can be summarized as follows. No deaths and no apparent clinical signs were observed. Body weights and food consumption were decreased at 40 mg/kg in the 2-week study along with testis and epididymis weights. In the 4-week study, epididymis weights were decreased at 20 mg/kg. The rats treated with 20 mg/kg in the 4-week study and those treated with 40 mg/kg in the 2-week study showed decrease of germ cells, exfoliation of germ cells, vacuolar degeneration of Sertoli cell and cell debris in epididymal ducts on histopathological observation. MMS impairment of spermatogenesis was confirmed by stage analysis. It was concluded that a treatment period of 2 weeks is sufficient to allow evaluation of toxic effects of MMS on the male reproductive organs.

Administration, Oral↗
PubMed2000

Laboratory evaluation of welder's exposure and efficiency of air duct ventilation for welding work in a confined space.

CO2 arc welding in a confined space was simulated in a laboratory by manipulating a welding robot which worked in a small chamber to experimentally evaluate the welder's exposure to welding fumes, ozone and carbon monoxide (CO). The effects of the welding arc on the air temperature rise and oxygen (O2) concentration in the chamber were also investigated. The measuring points for these items were located in the presumed breathing zone of a welder in a confined space. The time averaged concentrations of welding fumes, ozone and CO during the arcing time were 83.55 mg/m3, 0.203 ppm and 0.006%, respectively, at a welding current of 120A-200A. These results suggest serious exposure of a welder who operates in a confined space. Air temperature in the chamber rose remarkably due to the arc heat and the increase in the welding current. No clear decrease in the O2 concentration in the chamber was recognized during this welding operation. A model of air duct ventilation was constructed in the small chamber to investigate the strategy of effective ventilation for hazardous welding contaminants in a confined space. With this model we examined ventilation efficiency with a flow rate of 1.08-1.80 m3/min (ventilation rate for 0.40-0.67 air exchanges per minute) in the chamber, and proved that the exposure level was not drastically reduced during arcing time by this air duct ventilation, but the residual contaminants were rapidly exhausted after the welding operation.

Carbon Dioxide↗
PubMed2000

Numerical simulations to determine the most appropriate welding and ventilation conditions in small enclosed workspace.

In order to improve arc welding work in a small enclosed workspace, numerical simulations were conducted to find the most appropriate welding and ventilation conditions, such as welding currents, hood position and flow rates with no blowhole formation. In the simulations, distributions of airflow vectors and fume concentrations were calculated for two hood opening positions: one faced a welder's breathing zone, the other a contaminant source. As a result it was predicted that a hood opening facing a breathing zone remarkably lowered the fume concentration in the breathing zone compared with that facing a contaminant source. The reliability was confirmed in CO2 arc welding experiments in the enclosed workspace by using a welding robot. In addition, the number of blowholes in welds, examined with x-ray, decreased with the increase in the welding current and with the decrease in the exhaust flow rate. These results showed that the fume concentration near welder's breathing zone and the number of blowholes could be reduced effectively by appropriate selection of the welding current and hood position, and it was confirmed that the numerical simulations were sufficiently useful to predict these appropriate welding conditions.

Air Movements↗
PubMed2000

[Comparison of combined operation and nasal CPAP treatments for sleep disorders].

UNLABELLED: Uvulopalatopharyngoplasty (UPPP) and nasal CPAP are used for the treatment of obstructive sleep apnea syndrome (OSAS) in different institutions. Although OSAS results from an abnormality in the soft-palate, almost no reports have been made on the selection of UPPP or nasal CPAP procedures according to the type of abnormality. The most probable reason for this is that a comparison of treatment methods in individuals cases is difficult. We performed CPAP titration before and after operations, and compared the treatment methods, and evaluated the medical therapy. METHOD: A sleep polygraph was performed on the first night, and cases diagnosed as OSAS received CPAP titration on the second night. The blocked region was identified by endoscopic examination. The results of the operation were evaluated after 1-2 months, and apnea hypopnea index (AHI) improvements of less than 50% received a second CPAP titration. RESULTS: The operation results were poor for cases where endoscopic examination showed full-circumference palatal type, and good for soft palate and tonsillar type abnormalities. When endoscopic examinations were performed in conjunction with nasal CPAP, the treatment was observed to act on the soft palate and expand the air way in all cases. Nasal CPAP was effective in cases with full-circumference palatal abnormalities because in these cases, the pressure was caused by inflamma. Combined medical treatments were effective in cases where CPAP alone was ineffective because the pressure was too high.

Adult↗
PubMed2000

[Gene examination methods (detection and genotyping of resistant genes)--metallo-beta-lactamase].

Metallo-beta-lactamases have a hydrolysing activity against various beta-lactams including carbapenems, and beta-lactamase inhibitors such as clavulanic acid and sulbactum. Infections caused by metallo-beta-lactamase producing gram-negative bacteria are becoming a serious problem in Japanese clinical settings despite the recent progress in medical technology. Current screening methods can not distinguish metallo-beta-lactamase producers from those producing AmpC beta-lactamase. Here we show a convenient method of detecting metallo-beta-lactamase producers using a thiol compound(2-mercaptopropionic acid) as well as a PCR method with metallo-beta-lactamase gene specific primers.

Bacteriological Techniques↗
PubMed1999

Genetic association between alpha-2 macroglobulin and Japanese sporadic Alzheimer's disease.

Alpha-2 macroglobulin (encoded by the gene A2M) is a serum pan-protease inhibitor that may be related with the pathogenesis of Alzheimer's disease (AD) because of its ability to mediate amyloid beta degradation. Recently, several groups have reported that the five-nucleotides deletion in A2M gene at the 5' splice site of exon 18 might increase risk for AD. In the present study, therefore, this mutation was studied in 69 healthy controls and 55 sporadic AD cases by polymerase chain reaction- restriction fragment length polymorphism method. The allelic frequencies with the deletion (A2M-2) are 9.4 and 6.4% in the control and AD groups, respectively. There is no significant difference in the A2M-2 frequencies between the controls and sporadic AD cases. This is the first report to study the frequencies of A2M-2 in Japanese AD cases, suggesting its no genetic association with sporadic AD.

Adult↗
PubMed1999

The kinase inhibitor fasudil (HA-1077) reduces intimal hyperplasia through inhibiting migration and enhancing cell loss of vascular smooth muscle cells.

Smooth muscle cell (SMC) migration plays an important role in restenosis after angioplasty. Myosin phosphorylation is necessary for cell migration. Fasudil is an inhibitor of protein kinases, including myosin light chain kinase and Rho associated kinase, thereby inhibiting myosin phosphorylation, and it has been clinically used to prevent vasospasm following subarachnoid hemorrage. Based on these findings, we examined the anti-migrative action of fasudil. In SMC (SM-3), fasudil (1-100 microM) inhibited SMC migration in a dose-dependent manner (p < 0.001). Fasudil suppressed actin stress fiber formation dose dependently. In rabbit carotid artery, fasudil (10 mg/kg/day) markedly reduced intimal hyperplasia 14 days following balloon injury. Cell kinetic study showed that fasudil did not affect proliferation but enhanced cell loss in the media after injury. We concluded that fasudil reduced neointimal formation after balloon injury through both inhibiting migration and enhancing cell loss of medial SMC.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1999

A new mode of B12 binding and the direct participation of a potassium ion in enzyme catalysis: X-ray structure of diol dehydratase.

BACKGROUND: Diol dehydratase is an enzyme that catalyzes the adenosylcobalamin (coenzyme B12) dependent conversion of 1,2-diols to the corresponding aldehydes. The reaction initiated by homolytic cleavage of the cobalt-carbon bond of the coenzyme proceeds by a radical mechanism. The enzyme is an alpha2beta2gamma2 heterooligomer and has an absolute requirement for a potassium ion for catalytic activity. The crystal structure analysis of a diol dehydratase-cyanocobalamin complex was carried out in order to help understand the mechanism of action of this enzyme. RESULTS: The three-dimensional structure of diol dehydratase in complex with cyanocobalamin was determined at 2.2 A resolution. The enzyme exists as a dimer of heterotrimers (alphabetagamma)2. The cobalamin molecule is bound between the alpha and beta subunits in the 'base-on' mode, that is, 5,6-dimethylbenzimidazole of the nucleotide moiety coordinates to the cobalt atom in the lower axial position. The alpha subunit includes a (beta/alpha)8 barrel. The substrate, 1,2-propanediol, and an essential potassium ion are deeply buried inside the barrel. The two hydroxyl groups of the substrate coordinate directly to the potassium ion. CONCLUSIONS: This is the first crystallographic indication of the 'base-on' mode of cobalamin binding. An unusually long cobalt-base bond seems to favor homolytic cleavage of the cobalt-carbon bond and therefore to favor radical enzyme catalysis. Reactive radical intermediates can be protected from side reactions by spatial isolation inside the barrel. On the basis of unique direct interactions between the potassium ion and the two hydroxyl groups of the substrate, direct participation of a potassium ion in enzyme catalysis is strongly suggested.

Amino Acid Sequence↗
PubMed1999

Crystal structure of carboxylase reaction-oriented ribulose 1, 5-bisphosphate carboxylase/oxygenase from a thermophilic red alga, Galdieria partita.

Ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco, EC 4.1.1. 39) obtained from a thermophilic red alga Galdieria partita has the highest specificity factor of 238 among the Rubiscos hitherto reported. Crystal structure of activated Rubisco from G. partita complexed with the reaction intermediate analogue, 2-carboxyarabinitol 1,5-bisphosphate (2-CABP) has been determined at 2.4-A resolution. Compared with other Rubiscos, different amino residues bring the structural differences in active site, which are marked around the binding sites of P-2 phosphate of 2-CABP. Especially, side chains of His-327 and Arg-295 show the significant differences from those of spinach Rubisco. Moreover, the side chains of Asn-123 and His-294 which are reported to bind the substrate, ribulose 1,5-bisphosphate, form hydrogen bonds characteristic of Galdieria Rubisco. Small subunits of Galdieria Rubisco have more than 30 extra amino acid residues on the C terminus, which make up a hairpin-loop structure to form many interactions with the neighboring small subunits. When the structures of Galdieria and spinach Rubiscos are superimposed, the hairpin region of the neighboring small subunit in Galdieria enzyme and apical portion of insertion residues 52-63 characteristic of small subunits in higher plant enzymes are almost overlapped to each other.

Algal Proteins↗
PubMed1999

Tranilast suppresses vascular chymase expression and neointima formation in balloon-injured dog carotid artery.

BACKGROUND: Activation of vascular chymase plays a major role in myointimal hypertrophy after vascular injury by augmenting the production of angiotensin (ANG) II. Because chymase is synthesized mainly in mast cells, we assumed that the chymase-dependent ANG II formation could be downregulated by tranilast, a mast cell-stabilizing antiallergic agent. We have assessed inhibitory effects of tranilast on neointima formation after balloon injury in the carotid artery of dogs, which share a similar ANG II-forming chymase with humans, and further explored the pathophysiological significance of vascular chymase. METHODS AND RESULTS: Either tranilast (50 mg/kg BID) or vehicle was orally administered to beagles for 2 weeks before and 4 weeks after balloon injury. Four weeks after the injury, remarkable neointima was formed in the carotid arteries of vehicle-treated dogs. Chymase mRNA levels and chymaselike activity of vehicle-treated injured arteries were increased 10.2- and 4.8-fold, respectively, those of uninjured arteries. Angiotensin-converting enzyme (ACE) activity was slightly increased in the injured arteries, whereas ACE mRNA levels were not. Tranilast treatment completely prevented the increase in chymaselike activity, reduced the chymase mRNA levels by 43%, and decreased the carotid intima/media ratio by 63%. In vehicle-treated injured arteries, mast cell count in the adventitia showed a great increase, which was completely prevented by the tranilast treatment. Vascular ACE activity and mRNA levels were unaffected by tranilast. CONCLUSIONS: Tranilast suppressed chymase gene expression, which was specifically activated in the injured arteries, and prevented neointima formation. Suppression of the chymase-dependent ANG II-forming pathway may contribute to the beneficial effects of tranilast.

Animals↗
PubMed1999

A study of motor dysfunction associated with schizophrenia based on analyses of movement-related cerebral potentials and motor conduction time.

BACKGROUND: Several reports have shown that schizophrenics have motor dysfunction. The aim of this study was to identify the site of the nerve damage responsible for the motor dysfunction in schizophrenics by measuring both movement-related cerebral potentials (MRCPs) and motor conduction times. METHODS: The subjects were 27 patients and 31 controls. There was no significant difference in age, nor in the length of the subjects' arms between the two groups. MRCPs were recorded during voluntary self-paced index movements of the thumb. The motor nerve conduction time was determined by magnetically stimulating the motor cortex and the spinal root. RESULTS: Six of 27 schizophrenics had normal MRCPs, but the remaining 21 showed abnormal MRCPs. Of the 31 controls, 27 were normal, whereas 4 showed abnormal MRCPs. The difference between the two groups was significant; however, no significant differences were found in the motor conduction times, the motor root conduction times, or the central motor conduction times between the two groups. CONCLUSIONS: Our results suggest that the responsible focus of motor nerve disorder in schizophrenia lies in the motor-integrating system in frontal lobe, and not in the nervous conduction system from the brain to the muscles.

Adult↗
PubMed1999

Novel insight into the copper-ligand geometry in the crystal structure of Ulva pertusa plastocyanin at 1.6-A resolution. Structural basis for regulation of the copper site by residue 88.

The crystal structure of plastocyanin from a green alga, Ulva pertusa, has been determined at 1.6-A resolution. At its copper site, U. pertusa plastocyanin has a distorted tetrahedral coordination geometry similar to other plastocyanins. In comparison with structures of plastocyanins reported formerly, a Cu(II)-Sdelta(Met92) bond distance (2.69 A) is shorter by about 0.2 A and a Cu(II)-Sgamma(Cys84) distance is longer by less than 0.1 A in U. pertusa plastocyanin. These subtle but significant differences are caused by the structural change at a His-Met loop (His87-Met92) due to an absence of a O(Asp85)-Ogamma(Ser88) hydrogen bond which is found in Enteromorpha prolifera plastocyanin. In addition, poplar and Chlamydomonas reinhardtii plastocyanins with a glutamine at residue 88 have a weak cation-pi interaction with Tyr83. This interaction lengthens the Cu(II)-Sdelta(Met92) bond of poplar and C. reinhardtii plastocyanins by 0.14 and 0.20 A, respectively. As a result of structural differences, U. pertusa plastocyanin has a less distorted geometry than the other plastocyanins. Thus, the cupric geometry is finely tuned by the interactions between residues 85 and 88 and between residues 83 and 88. This result implies that the copper site is more flexible than reported formerly and that the rack mechanism would be preferable to the entatic theory. The His-Met loop may regulate the electron transfer rate within the complex between plastocyanin and cytochrome f.

Amino Acid Sequence↗
PubMed1999

Expression of vasa(vas)-related genes in germline cells and totipotent somatic stem cells of planarians.

Planarians are known for their strong regenerative ability. This ability has been considered to reside in the totipotent somatic stem cell called the "neoblast." Neoblasts contain a unique cytoplasmic structure called the "chromatoid body," which has similar characteristics to the germline granules of germline cells of other animals. The chromatoid bodies decrease in number and size during cytodifferentiation and disappear in completely differentiated cells during regeneration. However, germ cells maintain the chromatoid body during their differentiation from neoblasts. These observations suggest that the chromatoid body is concerned with the totipotency of cells. To understand the molecular nature of the chromatoid body in the neoblast, we focused on vasa (vas)-related genes, since VAS and VAS-related proteins are known to be components of the germline granules in Drosophila and Caenorhabditis elegans. By PCR, two vas-related genes (Dugesia japonica vasa-like gene, DjvlgA and DjvlgB) were isolated, and they were shown to be expressed in germ cells. Interestingly, DjvlgA was also expressed in a number of somatic cells in the mesenchymal space. In regenerating planarians, accumulation of DjvlgA-expressing cells was observed in both the blastema and the blastema-proximal region. In X-ray-irradiated planarians, which had lost regenerative capacity, the number of DjvlgA-expressing cells decreased drastically. These results suggest that the product of DjvlgA may be a component of the chromatoid body and may be involved in the totipotency of the neoblast.

Amino Acid Sequence↗
PubMed1999

Pharmacokinetics of cisplatin in analbuminemic rats.

The effect of protein binding on the pharmacokinetics of cisplatin (cis-diamminedichloroplatinum (II); CDDP) has been studied in analbuminemic rats, which genetically lack albumins, in comparison with normal rats. CDDP was reported to highly bind to serum components, and the major binder was thought to be an albumin. However, there were no significant differences in the serum disappearance profiles of platinum after intravenous (iv) bolus injection of CDDP to analbuminemic rats as compared with normal rats. The total body clearance, Cl(tot), of platinum in normal rats was 48.7+/-22.0 mL h(-1) (5 mg kg(-1)), 55.9+/-4.04 mL h(-1) (10 mg kg(-1)) and 49.0+/-3.57 mL h(-1) (20 mg kg(-1)), whereas Cl(tot) in analbuminemic rats was 52.0+/-8.48 mL h(-1) (5 mg kg(-1)), 62.9+/-10. 8 mL h(-1) (10 mg kg(-1)) and 62.8+/-6.81 mL h(-1) (20 mg kg(-1)). The serum blood urea nitrogen (BUN) and creatinine levels at 6 h after iv injection were higher in both groups of rats who received CDDP than those of pre-dose level. However, there were no significant differences in the renal function tests between analbuminemic rats and normal rats. The binding of CDDP to the serum samples obtained from analbuminemic rats and normal rats was measured by a centrifuging filtration method. The binding percentages were 68.0+/-5.9% (2.0 microg mL(-1)), 56.8+/-4.1% (5.0 microg mL(-1)) and 64.6+/-4.4% (10.0 microg mL(-1)) in analbuminemic rats and 52.9+/-3.5% (2.0 microg mL(-1)), 52.2+/-3.4% (5.0 microg mL(-1)), 56.9+/-1.9% (10.0 microg mL(-1)) in normal rats. Higher binding percentages were obtained in analbuminemic rats than in normal rats. In vitro binding studies under the two incubation conditions (5 min and 2 h) showed that the binding percentages of CDDP to serum proteins were 59.2+/-3.2% (5 min) and 72.3+/-6.5% (2 h) for albumin, 42.3+/-1.9% (5 min) and 39.5+/-2.5% (2 h) for alpha(1)-acid glycoprotein (AAG) and 51.7+/-5.3% (5 min) and 49. 2+/-1.9% (2 h) for gamma-globulin. From these studies, it was elucidated that albumin is not the major ligand in the rat serum and that other proteins also have important roles in the pharmacokinetics of CDDP.

Animals↗