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Biomedical subjects

H Miyauchi

Publications and source records attributed to H Miyauchi.

At least 19 recordsLinked to original sources

Direct determination of interfacial magnetic moments with a magnetic phase transition in Co nanoclusters on Au(111).

The spin, in-plane and out-of-plane orbital and magnetic dipole moments of almost purely interfacial Co atoms were directly determined for Au/2-monolayer Co nanoclusters/Au(111) by angle-dependent magnetic circular x-ray dichroism (MCXD) measurements. The field- and temperature-dependent MCXD evidences a ferromagnetic(FM)-to-superparamagnetic phase transition in single-domain clusters with decreasing size. The interfacial moments are remarkably enhanced as compared with bulk values, verifying theoretical predictions. The FM clusters show strong perpendicular magnetic anisotropy, providing promise of applications for nanoscale magnetic bits.

Journal Article↗

Close correlation between the magnetic moments, lattice distortions, and hybridization in LaMnO3 and La(1-x)Sr(x)MnO3+delta: doping-dependent magnetic circular X-ray dichroism study.

The first observation of a magnetic circular x-ray dichroism (MCXD) at the Mn L2,3 core edges in antiferromagnetic LaMnO3 shows canted spin and orbital ( m(orb)) moments arising from lattice distortions. An L2,3-edge MCXD in ferromagnetic metals and insulators, La1-xSr(x)MnO3+delta, reveals that m(orb) of Mn strongly depends on x in the metallic regime but remains unchanged with the metal-to-insulator transition (x approximately 0.16). An O K-edge MCXD, which shows m(orb) of O caused by 2p-3d hybridization, is much larger in the ferromagnetic metal than insulator phases, sharply contrasting with m(orb) of Mn. Our findings indicate a close magnetism-lattice-hybridization coupling.

Journal Article↗

alpha-Keto heterocycle inhibitors of fatty acid amide hydrolase: carbonyl group modification and alpha-substitution.

Two sets of novel analogues of the recently disclosed alpha-keto heterocycle inhibitors of fatty acid amide hydrolase (FAAH), the enzyme responsible for regulation of endogenous oleamide and anandamide, were synthesized and evaluated in order to clarify a role of the electrophilic carbonyl group and structural features important for their activity. Both the electrophilic carbonyl and the degree of alpha-substitution markedly affect inhibitor potency.

Amidohydrolases↗

Does the polymorphism of cytochrome P-450 2E1 affect the metabolism of N,N-dimethylformamide? Comparison of the half-lives of urinary N-methylformamide.

The aim of this study was to clarify whether phenotypic variation exists when subjects with different genotypes of cytochrome P450 2E1 (CYP2E1) are exposed to N,N-dimethylformamide (DMF). The genotypes of CYP2E1 were confirmed in 123 healthy male volunteer subjects. Of the 123 subjects, the numbers of c1 homozygotes, c2 heterozygotes, and c2 homozygotes were 77, 45, and 1, respectively. Seven of the c1 homozygotes, five of the c2 heterozygotes, and the one c2 homozygote (mean age: 22.7 years, range: 20-27 years) were exposed to DMF vapor twice, once via the skin and once via the lung, for a total of 8 h per subject at a concentration below 10 ppm, the occupational exposure limit recommended by the Japan Society for Occupational Health, the American Conference of Governmental and Industrial Hygienists, and Deutsche Forschungsgemeinschaft, at 27 degrees C and 44% relative humidity. Exposure levels were 6.2+/-1.0 ppm in dermal exposure and 7.1+/-1.0 ppm in inhalation exposure. Urine samples were collected until 72 h after exposure. The half-lives of urinary N-methylformamide (NMF) were obtained as the phenotype. The average urinary NMF half-lives of the c1 homozygotes, the c2 heterozygotes, and the c2 homozygote were 3.86+/-1.90, 4.38+/-1.53, and 4.2 h after dermal exposure, and 1.58+/-0.42, 1.84+/-0.61, and 3.2 h after respiratory exposure. The NMF half-lives of the c1 homozygotes were not significantly different from those of the c2 heterozygotes, and there were no differences between the NMF half-lives on the subjects with and without the c2 allele. Even though the data were obtained from only one c2 homozygote, it is noteworthy that the NMF half-life of this subject was slightly less than that of the c1 homozygotes after respiratory exposure.

Administration, Cutaneous↗

N,N-dimethylformamide: significance of dermal absorption and adjustment method for urinary N-methylformamide concentration as a biological exposure item.

OBJECTIVES: To clarify the potential for dermal absorption of N,N-dimethylformamide (DMF) (CAS No. 68-12-2) vapor, and the appropriate adjustment method and the half-lives of urinary concentrations of N-methylformamide (NMF) as the biological exposure item of DMF. METHODS: Thirteen healthy male volunteers (mean age: 22.7 years, range: 20-27) were exposed to DMF vapor twice, via both the skin and the lung, for 4 h at concentrations below 10 ppm, the recommended occupational exposure limit set by the Japan Society for Occupational Health, the American Conference of Governmental and Industrial Hygienists, and Deutsche Forschungsgemeinschaft, under conditions of 27 degrees C and 44% humidity. Each volunteer was exposed to DMF via the skin in a whole-body type exposure chamber and outside the chamber, via the lung by a respirator connected to the chamber. Exposure levels were 6.2 +/- 1.0 ppm in dermal exposure and 7.1 +/- 1.0 ppm in inhalation exposure. Urine samples were collected at every opportunity until 72 h after exposure; and NMF, as well as volume, creatinine, and specific gravity were measured. Dermal and inhalation intakes were compared after adjusting concentrations. RESULTS AND CONCLUSIONS: DMF vapor absorptions via the skin and the lung were estimated to be 40.4 and 59.6%, respectively. Workers need to be aware of the risk of dermal absorption of DMF vapor as well as of the liquid. Though NMF concentrations adjusted by creatinine, specific gravity, and urinary volume showed good correlation with total NMF excretion and the absolute amount of NMF at each sampling time, creatinine-adjusted NMF concentration correlated better than the others. The biological half-life of urinary NMF after dermal exposure, 4.75 +/- 1.63 h, was longer than that after respiratory exposure, 2.42 +/- 0.63 h.

Adult↗

Insertion polymorphism of CYP2E1 and urinary N-methylformamide after N,N- dimethylformamide exposure in Japanese workers.

OBJECTIVES: This study examined whether consideration of the *1C/*1D CYP2E1 insertion polymorphism is important for interpreting the biological monitoring of exposure to N,N-dimethylformamide (DMF) in Japanese workers. METHODS: The insertion genotype, airborne DMF exposure on the last day of a work week, and NMF in urine sampled just after the last workshift of the week were determined in 44 male and female Japanese workers. RESULTS AND CONCLUSIONS: The allelic frequency of this CYP2E1 polymorphism was 0.261 in this Japanese population of workers. The CYP2E1 insertion polymorphism did not contribute to NMF levels even after consideration of BMI or alcohol intake. The results indicate that CYP2E1 insertion polymorphism does not appear to be an important determinant for the interpretation of biological exposure to DMF by the measurement of urinary NMF.

Adult↗

Simultaneous determination of glycyrrhizin, glycyrrhetic acid and glycyrrhetic acid mono-glucuronide in Shakuyaku-kanzo-to incubated with rat feces by semi-micro high-performance liquid chromatography.

A method for semi-micro high-performance liquid chromatography (HPLC) has been established for the simultaneous determination of glycyrrhizin (GL), glycyrrhetic acid (GA) and glycyrrhetic acid mono-glucuronide (GAMG) in incubation mixtures of rat feces with Shakuyaku-kanzo-to decoction (combination of licorice root and peony root). The analysis could be accomplished within 20 min with a TSKgel ODS-80TsQA (150 x 2.0 mm i.d.) column by linear gradient elution using a mobile phase containing aqueous phosphoric acid and acetonitrile at a flow rate of 0.2 ml x min(-1), a thermostatic oven at 25 degrees C, and detection at 254 nm. The detection limits of these compounds were 0.1-0.85 pmol per injection (5 microl). The concentrations of GL and its metabolites in the incubation mixture after continuous consumption of Shakuyaku-kanzo-to were significantly different compared with those of untreated control. GL-hydrolysis of rat feces was enhanced by pre-consumption of Shakuyaku-kanzo-to.

Anaerobiosis↗

Causal relationship between a case of severe hepatic dysfunction and low exposure concentrations of N,N-dimethylformamide in the synthetics industry.

A 19-year-old man suffered hepatic dysfunction after 5 months of exposure to N,N-dimethylformamide (DMF) at his job in the synthetic resins industry. Laboratory data revealed elevated levels of AST (578 IU/l), ALT (1193 IU/l), and gamma-GTP (107 IU/l), no viral infection with HAV, HBV, or HCV, and no history or evidence of hepatic injury, although he did have a slight abdominal abnormality and swelling which was detected by palpation. His urinary N-methylformamide level, as a biological exposure index of DMF, was 42.8 mg/l, indicating 10-30 ppm of DMF exposure. After 2 months he was reinstated in two workplaces, the former where he worked in the morning and the other in the afternoon where environmental DMF concentrations were less than those in the former workplace. On the 18th day after his reinstatement, his liver function became exasperated again. After the second period of medication and one month of rest from work, he had fully recovered and was reinstated, but to a workshop without DMF exposure.

Adult↗

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (1)--Single oral and intravenous dose toxicity studies in rats].

A single oral dose toxicity study of Cefmatilen hydrochloride hydrate (S-1090) and a single intravenous dose toxicity study of its sodium salt (S-1090-Na) were conducted in rats. One dose level of 2000 mg potency/kg was set in both studies. Single oral dose toxicity study of S-1090 No deaths occurred. Diarrhea occurred on the dosing day and slightly soft feces lasted until 6 days after administration. These changes were considered to result from changes of intestinal flora induced by the antibiotic activity of S-1090. Reddish-brown feces (due to chelated products of S-1090 or its decomposition products with Fe3+ in the diet) were also observed until the next day after administration. Body weights increased favorably, and no S-1090-related pathological changes were observed. The oral lethal dose of S-1090 was estimated to be more than 2000 mg potency/kg. Single intravenous dose toxicity study of S-1090-Na No deaths occurred. The rats showed characteristic clinical signs such as hypoactivity, abnormal gait and hypopnea immediately after dosing, and some rats showed prone position or paleness of eyeballs and ear auricles in due course. These signs disappeared by 4 hr after administration. Slightly soft feces and reddish-brown feces were observed much the same as in the orally-treated rats. Body weights increased favorably. In the pathological examinations, slight cecal enlargement and increased basophilia, dilatation and calcification of the renal tubules in the kidney were observed. The intravenous lethal dose of S-1090-Na was estimated to be more than 2000 mg potency/kg.

Administration, Oral↗

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (4)--One- and three-month repeated oral dose toxicity studies in dogs].

One- or three-month repeated oral dose toxicity studies of Cefmatilen hydrochloride hydrate (S-1090) were conducted in beagle dogs. Doses were set at 25, 100 and 400 mg potency/kg/day in both studies. In both studies, no deaths occurred, and reddish-brown feces (due to chelated products of S-1090 and its decomposition products with Fe3+ in the diet) were observed in all treated groups. A transient excretion of reddish urine was observed in the 400 mg potency/kg group and a slight increase in plasma irons was also observed in the 100 and 400 mg potency/kg groups of both studies. However, as no changes suggesting anemia or hepatic injury were noted in these groups, the change of plasma irons was considered to have no toxicological significance. Plasma S-1090 concentrations increased in a manner less than dose-proportional in both studies. In the one-month toxicity study, no toxicologically significant changes, including the above findings, were noted, so the NOAEL was assessed to be 400 mg potency/kg/day. In the three-month toxicity study, urinalysis in the 400 mg potency/kg group revealed a positive reaction to occult blood and erythrocytes in sediments. In the pathological examinations, submucosal edema, hemorrhage, inflammatory cell infiltration and occasionally focal mucosal thickening were observed in the urinary bladder of the 400 mg potency/kg group. The cystisis was considered to result from chronic stimulation with the metabolite(s) of S-1090 in urine, and the reversibility was demonstrable upon one-month drug withdrawal. From these results, the NOAEL of S-1090 in the three-month toxicity study was assessed to be 100 mg potency/kg/day.

Administration, Oral↗

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (2)--Single oral dose toxicity study in dogs].

Cefmatilen hydrochloride hydrate (S-1090) was administered at 500 and 1000 mg potency/kg once orally to beagle dogs. No deaths occurred. Vomiting, diarrhea or mucous feces occurred on the dosing day, and reddish-brown feces (due to chelated products of S-1090 and its decomposition products with Fe3+ in the diet) were also observed on the dosing and next day. Increases of plasma urea nitrogen and iron were observed on the next day after dosing. No remarkable changes were noted in other examination items. The animals in both groups were considered to be exposed to a similar level of S-1090 based on the toxicokinetic data. The oral lethal dose of S-1090 in dogs was estimated to be more than 1000 mg potency/kg.

Administration, Oral↗

Fatty acid amide hydrolase substrate specificity.

Fatty acid amide hydrolase (FAAH), also referred to as oleamide hydrolase and anandamide amidohydrolase, is a serine hydrolase responsible for the degradation of endogenous oleamide and anandamide, fatty acid amides that function as chemical messengers. FAAH hydrolyzes a range of fatty acid amides, and the present study examines the relative rates of hydrolysis of a variety of natural and unnatural fatty acid primary amide substrates using pure recombinant rat FAAH.

Amidohydrolases↗

Exceptionally potent inhibitors of fatty acid amide hydrolase: the enzyme responsible for degradation of endogenous oleamide and anandamide.

The development of exceptionally potent inhibitors of fatty acid amide hydrolase (FAAH), the enzyme responsible for the degradation of oleamide (an endogenous sleep-inducing lipid), and anandamide (an endogenous ligand for cannabinoid receptors) is detailed. The inhibitors may serve as useful tools to clarify the role of endogenous oleamide and anandamide and may prove to be useful therapeutic agents for the treatment of sleep disorders or pain. The combination of several features-an optimal C12-C8 chain length, pi-unsaturation introduction at the corresponding arachidonoyl Delta(8,9)/Delta(11,12) and oleoyl Delta(9,10) location, and an alpha-keto N4 oxazolopyridine with incorporation of a second weakly basic nitrogen provided FAAH inhibitors with K(i)s that drop below 200 pM and are 10(2)-10(3) times more potent than the corresponding trifluoromethyl ketones.

Amidohydrolases↗

Internal carotid artery aneurysm visualized during successful endovascular treatment of carotid embolism.

We herein present a case of an internal carotid artery embolism associated with a hidden internal carotid artery aneurysm. The aneurysm was visualized during successful endovascular treatment of the carotid embolism. In retrospect, the aneurysm was at risk of rupture during the procedure. In the endovascular treatment of cerebral embolism, the possibility that aneurysms are hidden by emboli must be borne in mind. Care should be taken not to injure unidentified arterial walls while advancing a catheter blindly.

Aneurysm↗

Improvement of oral ingestion in patients with inoperable esophageal cancer treated with radiotherapy, chemotherapy and insertion of a self-expanding nitinol stent.

Radiotherapy, chemotherapy and self-expanding nitinol stent insertion were performed in patients with inoperable esophageal cancer to improve oral ingestion. Twelve patients underwent radiotherapy and chemotherapy. A stent was inserted in patients with dysphagia after radiotherapy and chemotherapy. Patients' capacity for oral ingestion was classified into three categories: grade I patients were able to ingest enough food; grade II patients could ingest food but required nutritional support; and grade II patients found it impossible to ingest anything. After radiotherapy and chemotherapy, the number of grade I patients increased from three to five but seven patients remained in grades II and III. Four grade II and III patients were treated with stents, after which dysphagia was reduced to grade I. In the grade I patients after treatment with radiotherapy and chemotherapy, the duration of grade I was on average 167 days and survival was 191 days. In the patients subjected to stent insertion, grade I lasted 65 days and survival was 149 days. Before the introduction of the stent, grade II patients died, on average, after 91 days. After the introduction of self-expanding nitinol stents, all patients could ingest enough food and were discharged.

Aged↗