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Biomedical subjects

Y Tatsuno

Publications and source records attributed to Y Tatsuno.

At least 37 records · Page 2Linked to original sources

Effect of the cytochrome P-450IIE1 genotype on ethanol elimination rate in alcoholics and control subjects.

We studied an influence of genetic polymorphisms in the cytochrome P-450IIE1 (CYP2E1) gene on ethanol elimination rate in alcoholic patients and healthy subjects. The CYP2E1 genotype was determined by polymerase chain reaction-restriction fragment length polymorphism method for 124 alcoholics and 54 healthy subjects. There was no significant difference in the gene frequency of CYP2E1 between alcoholics and healthy control subjects. Blood ethanol concentrations in the 65 alcoholics on admission ranged from 0.32 to 4.22 mg/ml. In the patients with the c1/c2 genotype, the elimination rate was significantly correlated with blood ethanol concentration. In each of the three genotypes of CYP2E1, the patients were divided into three groups based on ethanol concentrations. The average of the ethanol elimination rate in the patients with c1/c2 having blood ethanol levels of > or = 2.5 mg/ml was significantly higher than the rates in the two other groups of c1/c2. When blood ethanol levels were > or = 2.5 mg/ml, the elimination rate in the patients with c1/c2 was significantly higher than that in those with c1/c1. Regardless of the CYP2E1 genotype, the elimination rate in the alcoholics was higher than that in the control subjects when blood ethanol levels were < 1.0 mg/ml. These results suggest the possibility that the c2 allele of CYP2E1 Influences the rate of ethanol elimination at high ethanol levels. The rate of ethanol elimination was independent of liver disorder judged by serum total bilirubin values.

Adult↗

Identification of cholesta-3,5-dien-7-one by gas chromatography-mass spectrometry in the erythrocyte membrane of alcoholic patients.

Lipids and oxidized lipids were analyzed by gas chromatography-mass spectrometry in the erythrocyte membranes of alcoholic and control subjects. Cholesta-3,5-dien-7-one and cholesta-trienes were detected in alcoholic samples examined, but not in significant amounts in controls. Levels of polyunsaturated fatty acids (arachidonic acid, 20:4; docosahexaenoic acid, 22:6; and docosatetraenoic acid, 22:4) in alcoholic samples declined significantly, whereas cholesta-3,5-dien-7-one levels increased. A high level of total bilirubin was observed in most patients. A possible mechanism of the accumulation of cholesta-3,5-dien-7-one in the erythrocyte membrane of alcoholics is discussed.

Adult↗

Detection of measles virus nucleoprotein mRNA in autopsied brain tissues.

By means of RT-PCR, a portion of measles virus (MV) mRNA encoding nucleoprotein (NP) could be detected in 11 (18%) of 61 brain tissue samples obtained from administrative autopsy cases, who apparently had not suffered from subacute sclerosing panencephalitis (SSPE)-like central nervous system disorders. Most of the brain-derived NP sequences showed significant asynonymous nucleotide substitutions when compared with wild-type MV isolates and SSPE virus. Our present results suggest that MV commonly persists in the human brain without causing apparent clinical symptoms, probably due to decreased virus replication.

Adolescent↗

The effect of extraction methods. The kind of organ samples and the examination delay on the DNA yields and typing.

This study investigated the effect of DNA extraction methods, examination delay and the kind of organs samples to the DNA yields and typing. Thirty autopsy cases with postmortem period less than 12 hours were used as the sample resources. The DNA was successfully extracted from cerebral cortex, liver, spleen, lymph nodes, kidney, psoas muscle and prostate gland by Bar and Kirby methods. The spectrophotometric measurement showed that the spleen, lymph nodes, kidney and liver provided more DNA rather than the other organs. The agarose gel electrophoresis showed that the majority of the samples had High Molecular Weight-DNA (HMW-DNA) with variable degree of degradation. All of these DNA were successfully typed on the D1S80 locus using the PCR according to Kasai method. The spleen samples were collected from the same cases and stored at -20 degrees C for 1 to 6 weeks before the DNA extraction was performed. The analysis of the DNA extracted from these samples showed that the DNA yields and typing did not change significantly among the samples with examination delay up to 6 weeks after the sample collection. The comparison between the Bar and Kirby methods showed that the Kirby method resulted in more DNA yields with the same purity of DNA, but less HMW-DNA compared with Bar method.

Autopsy↗

Identification of four metabolites of 3-(phenylamino)alanine, a constituent in L-tryptophan products implicated in eosinophilia-myalgia syndrome, in rats.

3-(Phenylamino)alanine (PAA), a contaminant found in L-tryptophan tablets, has been discussed as a possible cause of eosinophilia-myalgia syndrome (EMS). We administered PAA (100 mg/kg) by gastric gavage to Wistar rats to determine its distribution and metabolism. We developed a purification procedure, using Bond Elut SCX cartridges followed by high performance liquid chromatography (HPLC) in order to determine levels of PAA. The level of PAA in blood was 4.22 micrograms/ml at 5 h and urinary excretion was 21.7 micrograms for 5 h and 84.6 micrograms between 5 and 24 h. The amount of PAA in the contents of the large intestine at 5 h was 0.76 microgram, indicating poor transfer of PAA to the large intestine. However, the highest concentration of PAA was 12.3 micrograms/g in the brain, indicating the passage of PAA through the blood-brain barrier. In addition to detecting PAA in the blood and organs, we also detected four metabolites of PAA in urine. We used gas chromatography mass spectrometry to identify PAA in rat liver, as well as N-(hydroxyphenyl)glycine, N-phenylglycine, 3-(pheylamino)lactic acid, and 3-(hydroxyphenylamino)-lactic acid in rat urine. These results suggest that the degradation pathway of PAA is similar to that of phenylalanine.

Administration, Oral↗

Acetaldehyde-induced formation of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid in rats.

1-Methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (MTCA) is one of the metabolites of peak E substance, which, based on epidemiological studies, has been thought to be a possible causative agent of the tryptophan-induced eosinophilia-myalgia syndrome. Acute ethanol and L-tryptophan administration in rats pretreated with cyanamide resulted in the formation of MTCA. Concentrations of MTCA were estimated at 27 ng/g in blood and 33 ng/g in kidneys. Chronic treatment with a liquid diet containing ethanol as 36% of the total calories for 6 weeks increased these levels. MTCA was barely observed in rats that had received acute or chronic ethanol in the absence of cyanamide, or in the cyanamide-tryptophan controls. Cyanamide facilitation of ethanol-dependent MTCA biosynthesis may be due to a potentiation of the blood level of acetaldehyde derived from ethanol. The blood acetaldehyde level in rats that had been acutely treated with cyanamide, ethanol and L-tryptophan was 348 microM, and averaged 503 microM in rats that received the same treatment after chronic consumption of ethanol. In contrast to the above findings, L-tryptophan intake promoted the formation of 1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (TCCA) in rats. This is the first report of MTCA in mammalian tissue during tryptophan and ethanol metabolism.

Acetaldehyde↗

Metabolism and distribution in the rat of peak E substance, a constituent in L-tryptophan product implicated in eosinophilia-myalgia syndrome.

Peak E substance, 1,1'-ethylidenebis[tryptophan], a contaminant found in L-tryptophan tablets, has been suggested as a causative agent for eosinophilia-myalgia syndrome (EMS). Peak E substance (50 mg/kg) was administered perorally to Wistar rats to determine its metabolism and distribution. A purification procedure using Bond Elut C8 cartridges followed by HPLC was developed for the determination of peak E substance. The plasma concentration of peak E substance was 136 ng/ml at 1 h, and urinary excretion was 717 ng at 5 h and 10342 ng for 5-24 h, showing slow excretion of peak E substance into urine. The amount of peak E substance in the contents of the large intestine at 5 h, however, was 3136 micrograms, much greater than urinary excretion for 24 h, indicating considerable transfer of peak E substance to large intestine without decomposition by gastric fluid in the stomach. We have detected for the first time not only the occurrence of peak E substance in plasma and urine, but also 1-methyl-tetrahydro-beta-carboline-3-carboxylic acid (MTCA) in blood and organs of rats treated with peak E substance, thereby suggesting MTCA as one of the the metabolites of peak E substance. The amount of MTCA in the contents of the large intestine as well as in urine of rats treated with peak E substance was significantly greater than in L-tryptophan-treated rats (50 mg/kg p.o.), demonstrating that MTCA was more readily produced from peak E substance than from L-tryptophan. Finally, we propose acetaldehyde-induced production of MTCA from peak E substance.

Animals↗

Accumulation of 1-methyl-tetrahydro-beta-carboline-3-carboxylic acid in blood and organs of rat. A possible causative substance of eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan.

1-Methyl-tetrahydro-beta-carboline-3-carboxylic acid (MTCA) may cause eosinophilia-myalgia syndrome (EMS) associated with ingestion of L-tryptophan. The distribution and excretion of MTCA were studied in rats which had received perorally a single 1.6 mg/kg dose of MTCA. MTCA concentrations in blood, kidney, liver, brain, heart, spleen, lung and gastrocnemius muscle were measured by HPLC combined with fluorometric detection. The concentration of MTCA in each organ reached a maximum at 1 h and then gradually declined. However, a significant level of MTCA still remained at 5 h, when 52% of ingested MTCA remained in the contents of the large intestine. Twenty-nine percent of the ingested MTCA was excreted in urine over the course of 24 h. A higher dose (10 mg/kg) of MTCA resulted in significant elevations in the concentrations and amounts of MTCA in the various organs. In addition, chronic treatment with a 10 mg/kg dose of MTCA for 6 weeks further increased the concentrations and amounts of MTCA in each organ. However, no histological changes were observed in any of the organs after chronic treatment. This is the first report which demonstrates accumulation of MTCA in the blood and various organs, including muscle, of rats.

Animals↗

[Recent advances in the study on the mechanism of brain injury].

A cerebral contusion and DAI (diffuse axonal injury) are practically very important in a medico-legal case of the closed head injury. In this paper, we will report the epitome of the recent advances in the study on the mechanism of them. Coup contusion can be mainly attributed to the skull inbending and/or the skull fracture which develop in the impact region. As to the mechanism of the contrecoup contusion, several theories are reported. During rotational movement of the head, intracerebral shear strains would be produced because of brain lag (Holbourn's rotation theory). Anatomical features of the skull plays an important role (Gurdjian). Relative movement between a brain and a skull induces intracranial cavitation due to pressure gradient (Gross's cavitation theory). Brain is injured by deformation pressure induced by skull deformation and acceleration one done by a movement of the head (Lindenberg). The last one is Courville's transmitted waves of force theory. As to DAI, there is Gennarelli's theory. During a rotational movement of a brain caused by high rate of angular acceleration operating for a long period, intracerebral shear strains occur and injure a brain. As to the brain injuries which include a cerebral contusion and DAI, two theories are reported. Centripetal progression of strains to the core of a brain injuries the brain (Ommaya). Natural frequency of impact determines the nature of resulting injury to the brain (Willinger).

Biomechanical Phenomena↗

Histo-pathological findings of abraded skins in the cases of automobile dragging.

We histologically examined skin which had been abraded by automobile dragging. In the first case, the victim was a 57-year-old drunken male. He was hit by a passenger car while walking on a road and dragged for a distance of 30 m. He soon died from the pelvic bone fractures. Extensive and deep abrasions were observed on both shoulders and the back. In the second case, a 20-year-old drunken male was lying on a road. He was run over by a passenger car and dragged for a distance of 800 m. During the dragging the car's underbody strongly compressed his thoraco-abdominal region and killed him by causing insufficiency in breathing. Deep abrasions were found in the right temporal region and right back at the waist. In the third case, when a 50-year-old woman was riding a moped it collided with a passenger car at an intersection and she fell to the ground. Soon after, she was run over by another passenger car and dragged for a distance of 718 m. The cause of death was profuse bleeding from the crushed right axillary artery and vein. Autopsy revealed very extensive and severe abrasions in the right upper arm, right axilla, lateral surface of the right chest and abdomen, right back, back pelvic region, and lateral surface of the right lower leg and foot. Especially in the arm, axilla and chest, the skin and soft tissues were worn away, muscles and bones were exposed, and the right axillary artery and vein were crushed.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Traffic↗

[A case of death within 3 hours due to systemic embolism of fat from tibial fractures].

We experienced a case dying of systemic fat embolism shortly after a traffic accident. The man of 83 years old suffered an accident by a car while wheeling his bicycle on a lane through rice fields. His both legs were run over by a wheel of the car. He was fully conscious for some while after the accident. However, while he was taken to a hospital by an ambulance, he suddenly lost consciousness and died 2 hours and 45 minutes after the accident. The autopsy examination revealed the severely fractured tibiae in both legs. The left clavicle and sternum as well as the ribs of both sides were also fractured. Organs in the thoracic and abdominal cavities were slightly congested. The histopathological examinations revealed fat droplets in the small vessels in interlobular connective tissues and many alveolar capillaries of the lungs, many glomeruli of the kidneys and a few capillaries in parietal region of the cerebrum.

Accidents, Traffic↗

Genetic polymorphism of alcohol and aldehyde dehydrogenase and the effects on alcohol metabolism.

Influence of genetic polymorphism at the alcohol dehydrogenase2 (ADH2) and aldehyde dehydrogenase2 (ALDH2) loci on ethanol elimination and blood acetaldehyde level was studied in healthy subjects. Polymorphic regions of the ADH2 and ALDH2 genes were amplified for genomic DNA by using the technique of polymerase chain reaction. The ADH2 genotype was determined by digestion with the restriction enzyme MaeIII and the ALDH2 genotype was defined by hybridization with sequence specific oligonucleotide probes. Both loci were typed for unrelated 58 individuals by using the above methods. The gene frequencies of each locus were estimated as follows; 0.31 and 0.69 for ADH2*1 and ADH2*2, respectively, and 0.73 and 0.27 for ALDH2*1 and ALDH2*2, respectively. These values were consistent with the Hardy-Weinberg equilibrium. Pedigree analysis of 6 families with 46 subjects on both loci confirmed Mendelian inheritance. In order to investigate differences in ethanol elimination among ADH2 and ALDH2 genotype groups, 0.4 g/kg body weight of ethanol was administered to 93 subjects whose genotypes of both loci were determined by the above methods and blood ethanol and acetaldehyde levels were measured. None of the subjects homozygous for the ALDH2*1 allele showed facial flushing and any increase in blood acetaldehyde level. All the homozygotes and heterozygotes with the ALDH2*2 allele exhibited facial flushing, and the former showed a marked increase in blood acetaldehyde level and the latter did a mild increase. On the other hand, the influence of the ADH2 genotype on blood acetaldehyde level was not significant. The values of Widmark's beta 60 (mg/ml/hr) and ethanol elimination rate (mg/kg/hr) showed significant differences among the three groups of the ALDH2 genotypes in each group of the three ADH2 genotypes, and in decreasing order of both the values were ALDH 2*1/*1, ALDH2*1/*2, ALDH2*/*2, However, there were no significant differences in the values among the ADH2 genotypes.

Acetaldehyde↗

Thymus of abused/neglected children.

Forty-six cases of child abuse/neglect autopsied during the period of 1967 to 1990 were investigated. The weight and histological findings of the thymus were compared with those of control children. In most abused and/or neglected children, the weight of the thymus decreased conspicuously. Involution correlated well to the degree and period of maltreatment. In cases without weight loss of the thymus, i.e. spasmodic abuse by a mentally deranged parent or foster parent, a short history of maltreatment was noted. On the other hand, marked involution was observed in cases of prolonged physical abuse and/or neglect. Microscopically, a decrease in the number and pyknosis of lymphocytes were observed in the involuted thymus. Atrophy of the thymus was more conspicuous in the cortex than in medulla. Immunohistochemically, CD-1a positive cells (immature thymocytes) decreased in cases with thymic involution. This involution appears to be an important index of the degree and duration of child abuse/neglect. Furthermore, thymic involution in the early stage of childhood may also be related to insufficiency of the immune system.

Age Factors↗

[Fracture of the cervical spine caused by blow in patient with ankylosing spondylitis--a report of an autopsy case].

Fracture of the cervical spine in a patient with ankylosing spondylitis is presented. A 43-year-old male was involved in a fight when drinking. He received blows to his face and the lower jaw, and fell backward on the street and died. The postmortem examination showed abrasions and subcutaneous hemorrhages on the face and the lower jaw. A transverse fracture was observed through the intervertebral disc space between the fifth and sixth cervical vertebrae. The cervical spinal cord was completely ruptured at the fracture site. Ossification of the supporting ligaments and anterior surface of dics were found. The spine was bony ankylosed. The alcohol levels of blood and urine were 2.95 and 3.84 mg/ml, respectively. The cause of death was paralysis of respiration. The victim had suffered from the ankylosing spondylitis for many years. His neck had no mobility. The X-ray films taken at age 42 showed complete ankylosis of the spine, so-called "bamboo" spine. It seemed that the blow to his face and the lower jaw caused hyperextension of the neck and easily caused the cervical fracture because of the loss of flexibility and fragility from osteoporosis in the ankylosed spine.

Adult↗

[Morphometric and pathologic studies of the brain in autopsied cases of Alzheimer-type dementia].

Human brain sections were analysed by computer-assisted quantitative morphometry. The brains, autopsied at the Department of Legal Medicine, Kobe University School of Medicine and the Medical Examiner's Office of Hyogo Prefecture, included 63 cases of acute death consisting of 49 cases of non-demented and 14 cases of Alzheimer's disease (AD) or senile dementia of Alzheimer-type (SDAT). As for patients of AD and SDAT, they were clinically diagnosed at some medical facilities in their life time. Histopathological diagnosis for AD and SDAT was confirmed by the presence of abundant senile plaques and neurofibrillary tangles. In the non-demented control aging, a modest atrophy occurred throughout the cerebral cortex except the occipital cortex, whereas no sign of atrophy was seen in the medullary white matter. In the AD and SDAT cases, both cortical gray and medullary white matter showed significantly higher degrees of atrophy than in the controls. A further detailed study indicated that the parietotemporal association cortex was specifically affected in the demented brain as compared with the normal aging.

Aging↗

Electrophoretic phenotyping of erythrocyte enzymes.

Erythrocyte acid phosphatase (EAP), esterase D (ESD) and phosphoglucomutase (PGM) phenotypes among the erythrocyte enzyme types of blood groups are surveyed and a modified cellulose acetate membrane isoelectric focusing (CAM-IEF) method for their exploration is described. The phenotyping procedures are usually classified as either equilibrium or non-equilibrium IEF. Equilibrium IEF, which is based on differences in pI values, includes three methods: (i) a narrow pH range of carrier ampholytes, (ii) a relatively narrow pH range of carrier ampholytes containing chemical separators and (iii) immobilized pH gradient gels. Among the three methods, immobilized pH gradients provides a better resolution of isozymes. Conversely, the disadvantages of immobilized pH gradients include longer focusing times and complex gel preparations. Moreover, immobilized pH gradients are unsuitable for stain analysis because of the insensitivity of PGM1 detection. A hybrid IEF system and a commercial immobilized pH gradient dry plate have overcome these problems. However, EAP typing is extremely expensive and ESD typing is not well distinguished by hybrid IEF. As each method has both merits and demerits, the most suitable technique should be selected based on the kind of erythrocyte enzyme types and sample conditions. On the other hand, non-equilibrium IEF is a rapid method because isozymes are detected on the basis of their charge differences under non-equilibrium conditions. Moreover, the appropriate addition separators increases the charge difference and provides a good resolution within a shorter time. Addition of more separators produces a narrow pH range in the gel and takes a substantially longer time to reach the optimum pH range for charge difference.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗

Endogenous formation of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3- carboxylic acid in man as the possible causative substance of eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan.

1-Methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (MTCA) is now thought to be a possible causative substance of eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan. In the present study a factor affecting endogenous formation of MTCA in 32 healthy men is studied. Urinary excretions of MTCA and 1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (TCCA) were measured by high-performance liquid chromatography (HPLC) with fluorometric detection after administration of a high or low protein diet as well as peroral tryptophan (0.5 g) or ethanol (0.4 g/kg). Blood ethanol and acetaldehyde levels were determined by gas chromatography after ethanol consumption. Both, the high protein diet and tryptophan resulted in a significant rise of urinary TCCA. In contrast, ethanol intake caused increased excretion of MTCA, though a relationship between blood acetaldehyde level and urinary excretion of MTCA was not shown. We showed for the first time that an elevation of urinary excretion of MTCA following ethanol consumption in man without ingestion of L-tryptophan tablets implicated eosinophilia-myalgia syndrome.

Acetaldehyde↗

A study on house fire victims: age, carboxyhemoglobin, hydrogen cyanide and hemolysis.

Correlation among age, concentrations of carboxyhemoglobin and hydrogen cyanide, oxygen density and hemolysis were studied in 120 house fire victims. Victims aged over 60 years comprised approximately 50% of the pooled subjects. Blood samples were mainly collected from the left ventricle, but sometimes from both the right and left ventricles. The concentration of carboxyhemoglobin ranged from 1-95%, of which 71 persons (59.7%) died with carboxyhemoglobin concentrations below 60%. Carboxyhemoglobin concentrations below 10% were found in 9 persons (7.5%). Most of these cases involved the elderly persons. In this paper, we report on the death of elderly victims as a result of low carboxyhemoglobin concentrations. A significant correlation of blood carboxyhemoglobin concentrations existed between the right and left ventricles. The concentration of carboxyhemoglobin in the left ventricle was significantly higher than that in the right. Two out of 31 victims whose hydrogen cyanide concentrations were determined, succumbed to hydrogen cyanide poisoning, having a high concentration of hydrogen cyanide and a low concentration of carboxyhemoglobin. On analysis, oxygen density was found to be low in 13 persons. A negative correlation was shown between carboxyhemoglobin concentration and hemolysis. Inasmuch as hemolysis may indicate the extent of heat dissociation, hemolysis should provide an index of carbon monoxide dissociation from carboxyhemoglobin. In the present study of victims, possible causes of death i.e., carbon monoxide gas poisoning, hydrogen cyanide poisoning, oxygen deprivation, burning, shock due to burns and others were estimated. The survival time for elderly victims was considered to be short.

Adolescent↗