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Biomedical subjects

H Miyauchi

Publications and source records attributed to H Miyauchi.

At least 19 recordsLinked to original sources
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

[A case of myotonic dystrophy showing proximal dominant muscle involvement but not myotonia].

A 45-year-old female had progressive difficulty in climbing stairs and standing from a chair for 10 years. She had binocular cataracts which were operated at the age of 42 years. On examination, she had marked muscle wasting in the proximal limbs, scapular and sternomastoid muscles. She presented as marked muscle weakness in the proximal portion of the lower extremities and moderate in the upper extremities and the legs. Deep tendon reflexes were absent in all limbs. There was no grip myotonia, or percussion myotonia of the thenar muscle and tongue. Myotonia was not elucidated even after the hands were exposed to cold water. Moreover, none of the examined muscles revealed insertion myotonic discharge on electromyography. Serum CK level was normal and IgG value decreased to 546 mg/dl. Muscle biopsy of the left biceps muscle showed the variation in fiber size, increased central nuclei and many fiber with pyknotic nuclear clumps on HE staining. Sarcoplasmic mass and ring fibers were also found on HE staining. There were a few percents of ragged-red fibers on Gomori-trichrome staining, and type 1 fiber atrophy was found on pH 4.5 ATP-ase staining. The expansion of lymphocyte CTG trinucleotide repeats in the myotonin protein kinase gene was about 733, so that she was diagnosed as having myotonic dystrophy (MD). MRI of skeletal muscles exhibited marked atrophy especially in the femoral region and the biceps muscle. This patient had the proximal dominant muscle weakness, and absent myotonia even on electromyographic examination, which are unusual clinical features of adult onset MD.

Atrophy↗
PubMed1998

Bovine lactoferrin stimulates the phagocytic activity of human neutrophils: identification of its active domain.

Bovine LF (bLF) at concentrations in the range of 50-250 micrograms/ml enhanced the phagocytic activity of human neutrophils as determined by measuring the incorporation of FITC-labeled latex beads by flow cytometry. The stimulatory effect of bLF was not abrogated by hydrolysis with pepsin. Bovine lactoferricin (bLFcin), which is a bactericidal fragment purified from a pepsin hydrolysate of bLF (bLFH), also enhanced the phagocytic activity, whereas, in contrast, the fraction of bLFH depleted of bLFcin showed no stimulatory effect. The phagocytosis-enhancing activity of bLF still remained after washing the neutrophils, following exposure to bLF. Also, bLF pretreatment of the latex beads stimulated their uptake. These results demonstrate that bLF is effective in promoting the phagocytic activity of human neutrophils. This activity appears to be due to its bLFcin domain and may involve dual mechanisms of direct binding to neutrophils and opsonin-like activity.

Animals↗
PubMed1998

Evidence on N-acetyltransferase allele-associated metabolism of hydrazine in Japanese workers.

Hydrazine (N2H4), which has been categorized as a weak carcinogen, is a chemical with the one of the largest production rates in Japan. We have investigated the effects of acetylation phenotypes on the metabolism of hydrazine. Genotypes of N-acetyl transferases, NAT2*, were determined using polymerase chain reaction for 297 male workers. Biological and exposure monitoring were also conducted. The rapid and intermediate acetylators accounted for 45% each, and the slow acetylators accounted for 10%. Biological half-lives were significantly different among the three acetylation phenotypes (analysis of variance, P < 0.05): 3.94+/-1.70 hours for slow acetylators, 2.25+/-0.37 hours for intermediate acetylators, and 1.86+/-0.67 hours for rapid acetylators. Among Japanese, rapid and intermediate acetylators are the major phenotypes, which is in sharp contrast with those among Caucasians. We conclude that biological monitoring should take genetic factors, which may vary dramatically among different populations, into account.

Adult↗
PubMed1998

The contribution of trace elements from smokeless powder to post firing residues.

The smokeless powders in 22 kinds of ammunitions seized from one of the Japanese gang groups were analyzed by scanning electron microscopy/energy dispersive X-ray microanalysis (SEM/EDX). Copper(Cu), sulfur(S), potassium(K), silicon(Si), aluminum(Al), calcium(Ca), iron(Fe), chlorine(Cl), and barium(Ba) were detected. Cu was found in all samples. One sample contained a high amount of Ba. One part of the burnt smokeless powder was found to contain Cu, K, Ca, Fe and S, the other part contained Cu, Fe, and zinc(Zn). It has been reported that the elements in gunshot residues originate from a bullet and/or a primer. However, this demonstrates that smokeless powder could be the source of some of the elements detected.

Aluminum↗
PubMed1998

A cross-sectional observation of the health effects of hydrazine hydrate and differences of its metabolism by NAT2 polymorphism.

OBJECTIVES: To summarize the results of two studies that attempted to clarify: (1) the health effects of hydrazine hydrate (HH) (N2H4 x H2O: CAS No. 7803-57-8); and (2) the influence of allelic polymorphism of N-acetyltransferase (NAT2) on the metabolism of HH. METHODS: A cross-sectional survey was carried out on 172 male HH-exposed workers and 125 male referent workers at five factories in Japan. The biological half-lives of HH after 1 h of exposure were determined in 12 workers, four workers in each of three NAT2 phenotypes. Clinical examinations were performed and acute and chronic subjective symptoms related to HH were examined by self-administered questionnaires. NAT2 phenotypes were assessed. RESULTS: No hydrazine was detected in either the breathing zones or the urine of the referent workers. The mean hydrazine concentration in the breathing zones, hydrazine and acetylhydrazine in urine, and the cumulative exposure level were 0.0109 ppm, 0.8660 micromol/g x Cr, and 2.80 ppm-years, respectively. There was no difference and no dose-dependent change in the health examination items between HH-exposed and referent workers after adjusting confounding factors, nor in terms of the differences of NAT2 phenotypes. Of 90 subjective symptoms, complaints of nightmares were significantly related to HH exposure. The half-life of urinary hydrazine and acetylhydrazine on rapid, intermediate, and slow phenotypes was 1.68, 3.01, and 4.46 h, respectively. CONCLUSION: This study suggested that current and cumulative exposure to HH did not affect the workers' health, and the half-life of the slow phenotype was longer than those of the rapid and intermediate phenotypes.

Adolescent↗
PubMed1997

Lactoferrin as a suppressor of cell migration of gastrointestinal cell lines.

The effects of lactoferrin (Lf), an iron-binding glycoprotein, on cell migration were investigated. Lf inhibited the cell migration of three gastrointestinal cell lines (Caco-2 cells, AGS cells, and IEC-18 cells) in vitro. Both iron-saturated (holo) and iron-depleted (apo) Lf showed this inhibitory effect. Chelation of iron in the culture medium by desferrioxamine did not affect the activity of either form of Lf. A pepsin hydrolysate of Lf exhibited effectiveness similar to that of intact Lf. These results demonstrate a novel activity of Lf and suggest a potential role for this molecule in gastrointestinal wound healing, which is independent of its iron-binding capacity.

Adenocarcinoma↗
PubMed1997

Beta-lactoglobulin suppresses melanogenesis in cultured human melanocytes.

The effects of whey proteins from bovine milk on melanogenesis in cultured human melanocytes were examined. Among the major protein components of milk whey including beta-lactoglobulin (BLG), alpha-lactalbumin, serum albumin, and IgG, only BLG exhibited the depigmenting effect at a concentration of 1 mg/ml. Also, BLG suppressed the activity of tyrosinase in these cells. Retinol, to which BLG is known to bind, slightly increased the pigmentation of the cells at concentrations in the range of 1-100 nM, and retinoic acid, a metabolite of retinol, exhibited a strong pigmentation-promoting effect within the same concentration range. Treatment of the cells with 1 mg/ml BLG completely abrogated the pigmentation induced by these A vitamins. These results demonstrate a novel biological activity of BLG and suggest that this activity is dependent on its ability to bind retinol.

Animals↗
PubMed1997

Pharmacological properties of YM17E, an acyl-CoA:cholesterol acyltransferase inhibitor, and diarrheal effect in beagle dogs.

YM17E (1,3-bis[[1-cycloheptyl-3-(p-dimethylaminophenyl)ureido]methyl]ben zene dihydrochloride) was found to be a potent inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT) in rabbit liver and intestine microsomes. Dixon plot analysis revealed that YM17E inhibited microsomal ACAT in a non-competitive manner. YM17E induced a marked decrease in serum cholesterol, especially in non-high-density lipoprotein (HDL) fractions, in cholesterol-fed rats and rats fed normal chow. Measurement of bile secretion after oral administration of YM17E in cholesterol-fed rats showed that the drug markedly accelerated the secretion of bile acids and neutral sterols. Furthermore, absorption of [3H]cholesterol from the gut of cholesterol-fed rats was significantly inhibited by YM17E. From these results, the hypocholesterolemic activity of YM17E in these animals resulted from both a decrease in cholesterol absorption from the gut and the stimulation of excretion of cholesterol from the liver into bile. However, YM17E caused secretory diarrhea in beagle dogs at near lipid lowering doses. When YM17E was administered at the same total dosage but divided into 5 daily administrations, the incidence of diarrhea was significantly reduced while its cholesterol lowering effect became stronger. These results suggest that the inhibition of intestinal and/or liver ACAT increases the risk of diarrhea development which, however, can be avoided by controlled drug administration in beagle dogs.

Animals↗
PubMed1997

Immunomodulatory effect of bovine lactoferrin pepsin hydrolysate on murine splenocytes and Peyer's patch cells.

The effects were examined of a pepsin hydrolysate of bovine lactoferrin on the proliferation of murine splenocytes. The hydrolysate enhanced [3H]thymidine uptake by splenocytes, but undigested bovine lactoferrin exerted an inhibitory effect. The hydrolysate had the ability to inhibit the blastogenesis that was induced by mitogens such as concanavalin A, phytohemagglutinin, and lipopolysaccharide; inhibition was similar to that with undigested lactoferrin. These results suggested that the hydrolysate contained both immunostimulatory and immunoinhibitory peptides. The stimulatory effect of the hydrolysate in the absence of mitogens was then explored in more detail using nonadherent splenocytes. The proliferative response of splenocytes to the hydrolysate was much greater in the fraction that was enriched with B cells than in the fraction that was enriched with T cells. The hydrolysate did not affect thymocyte proliferation. These data indicated that the adherent cells resembling macrophages and found among the splenocytes were not the target cells of the hydrolysate. The stimulatory effect of the hydrolysate was due to the activation of B cells by the hydrolysate and enhanced immunoglobulin production by splenocytes. Because the hydrolysate also enhanced the proliferation and immunoglobulin A production of Peyer's Patch cells, the immunostimulatory effect of the hydrolysate in vivo was examined using mice that had been orally immunized with cholera toxin. The concentrations of immunoglobulin A conjugated against cholera toxin in bile and in the intestinal contents of mice fed liquid diets containing 1% (wt/vol) lactoferrin hydrolysate were greater than those of mice fed control diets. This result suggested that the use of the lactoferrin hydrolysate is beneficial to enhance mucosal immunity.

Adjuvants, Immunologic↗