Search PubMed⌕ Search

Biomedical subjects

T Kawamoto

Publications and source records attributed to T Kawamoto.

At least 181 records · Page 10Linked to original sources
PubMed1994

Distribution of urinary hippuric acid concentrations by ALDH2 genotype.

OBJECTIVES: To clarify the relation between the genetic polymorphism of ALDH2 (low Km aldehyde dehydrogenase) and toluene metabolism. METHODS: The study subjects were 253 toluene workers (192 men and 61 women with an age range of 18-66). The genotypes of ALDH2 were classified by artificial restriction fragment length polymorphism into the homozygous genotype of normal ALDH2 (NN), the homozygous genotype of an inactive ALDH2 (DD), and the heterozygous genotype of normal and inactive ALDH2 (ND). The concentrations of hippuric acid (HA), the main metabolite of toluene, was determined in urine specimens of 253 toluene workers. The HA measurements in previous occupational health examinations were also referenced. The HA concentrations corrected for creatinine (HA/C) were compared with the biological exposure index (BEI) for toluene, which is 2.5 g/g creatinine. To estimate the toluene exposures, urinary o-cresol concentrations were also determined and compared with another BEI for toluene--that is, 1.0 mg urinary o-cresol/g creatinine. RESULTS: Incidence of each genotype in the toluene workers was almost the same as that in non-exposed controls who lived in the same area as the toluene workers. The incidence of each of the three genotypes also did not differ by smoking habit. Mean urinary HA concentrations were not significantly different in the groups with the different genotypes of ALDH2. The HA concentrations of > 70% of the 890 total samples were < 1.0 g/l. The number of urine samples > 3.0 g/l was 28 (5.4%) in the NN group and 19 (6.4%) in the ND group. No urine samples in the DD group were > 3.0 g/l HA. The distribution of urinary HA in the DD group was significantly different from those in both the NN and ND groups (P < 0.05). Seven (4.9%) of the 136 total specimens in the NN group and four (4.7%) of the 82 total specimens in the ND group exceeded the BEI. There were, however, no urine specimens that exceeded the BEI in the DD group. The maximum HA concentration after correction for creatinine in the DD group was 1.86 g/g creatinine. The percentages of urine specimens in which o-cresol concentrations exceeded this BEI were 14.3% in the NN group, 9.1% in the ND group, and 15.4% in the DD group. Therefore, the exposure rate for all three genotypic groups of workers was almost the same. CONCLUSIONS: The HA concentrations of toluene workers with ALDH2 DD genotype were lower than those of the NN and ND genotypes when they were exposed to relatively high concentrations of toluene. The exposures of the DD group were suspected to be underestimates because they were based on the BEI for the NN genotype.

Adolescent↗
PubMed1994

Serum hepatocyte growth factor in acute hepatic failure in comparison with acute hepatitis.

Serum hepatocyte growth factor (HGF) levels in patients with acute hepatic failure has been reported to increase. However, possible mechanisms responsible for HGF elevation in this syndrome remains to be determined. To explore the possible mechanisms, we measured serum HGF in patients with acute hepatic failure and self-limited acute hepatitis, using an immunoradiometric assay. Serum HGF levels in acute hepatic failure were 36-fold higher compared with those in acute hepatitis. Serum HGF values in acute hepatitis were significantly correlated with serum bilirubin and gamma-GTP levels, whereas those in acute hepatic failure were not. These clinical findings suggest that serum HGF levels in acute hepatic failure may be regulated by different mechanisms from those in self-limited acute hepatitis.

Acute Disease↗
PubMed1994

Craniofacial patterns of Japanese adults with various types of malocclusion: a counterpart analysis.

Craniofacial morphological characteristics of Japanese adults with various malocclusions were investigated. Cephalometric radiographs of 100 Class I, 100 Class II, and 100 Class III cases were selected and subjected to counterpart analysis as described by Enlow. Results of individuals with normal Class I occlusion revealed a mean value of 39.5 degrees for the angle of the middle cranial fossa relative to the posterior maxillary plane alignment (MCF/PM). This value was used as the basis for intrinsic alignment comparisons for all other skull points. Class I and II malocclusions were classified as either type A or B, depending on whether point A or B was protrusive in the functional occlusal plane (FOP). We found that type B was more common for both Class I and Class II malocclusion. Further, in both Classes, type B cases exhibited an underlying Class III character. We also noted that both B groups had different structural craniofacial patterns relative to those seen in A groups. Both dental Class IA and Class IB had a skeletal Class II tendency. The difference between Class IA and Class IIA, or between Class IB and Class IIB was slight but quantitative. Class III and Class IIA individuals had distinctly different and essentially opposite underlying patterns. Most compensatory effects were ineffective in both Class IIA and Class III groups. However, the composite compensatory result in Class IB case was, for the most part, effective.

Adolescent↗
PubMed1993

Fate of right ventricular hypertrophy in tetralogy of Fallot after corrective surgery.

To elucidate the reversibility of right ventricular (RV) myocardial hypertrophy in tetralogy of Fallot (TF), 30 patients underwent RV endomyocardial biopsies 1 to 25 years (mean 9.7 +/- 6.6) after corrective surgery. Myocardial cell diameter was evaluated by comparing histopathologic data with preoperative patients with TF and normal subjects. As a whole, postoperative cell diameter was smaller than that of age-matched preoperative patients with TF, and larger than that of age-matched normal subjects. In 7 patients without significant residual pulmonary stenosis whose preoperative data were also available, cell diameter significantly decreased after surgery (17.1 +/- 2.1 to 14.0 +/- 2.1 microns, p < 0.01). There was a positive correlation between postoperative cell diameter and age at study (p < 0.01). To negate the influence of age, cell diameter was expressed in terms of a percentage of age-matched normal values (percent cell diameter). There was no significant correlation between percent cell diameter and age at surgery, age at study or the follow-up periods. There were positive correlations between percent cell diameter and the following parameters: RV systolic pressure (p < 0.05), percent normal RV end-diastolic (p < 0.05) and end-systolic (p < 0.01) volumes. These results demonstrate that RV myocardial hypertrophy in TF can regress to some extent after corrective surgery if significant residual pulmonary stenosis is avoided.

Adolescent↗
PubMed1993

Extralysosomal degradation of high-density lipoproteins in a human hepatoma cell line, Mahlavu.

Lipoprotein metabolism has been investigated in a novel human hepatoma cell line, Mahlavu, which has been reported to possess the characteristics of hepatocytes. Low-density lipoprotein (LDL) was degraded by Mahlavu cells. LDL taken up by the cells suppressed intracellular cholesterol biosynthesis and promoted cholesterol esterification in a manner similar to that of HepG2 cells. High-density lipoprotein (HDL) was also degraded by Mahlavu cells, whereas it was not degraded by fibroblasts. We compared the mode of intracellular metabolism of HDL to that of LDL. In contrast to the LDL receptor pathway, the degradation of HDL was not inhibited by 100 microM chloroquine added to the medium, indicating that the degradation may not occur in lysosomes. Cholesterol taken up as HDL-cholesterol by the Mahlavu cells had no effect on the intracellular biosynthesis of cholesterol nor on cholesterol esterification. The conditioned media in which Mahlavu cells had been cultured did not promote the degradation of HDL, suggesting that HDL is degraded intracellularly. These data suggest that HDL is taken up and degraded by the liver cells in contrast to extrahepatic peripheral cells such as fibroblasts and macrophages in which the degradation of HDL does not occur. The results indicate that HDL-associated cholesterol may be processed via a pathway different from that of LDL metabolism and that the degradation of HDL occurs extralysosomally.

Carcinoma, Hepatocellular↗
PubMed1993

Congenitally defective aldosterone biosynthesis in humans: inactivation of the P-450C18 gene (CYP11B2) due to nucleotide deletion in CMO I deficient patients.

CYP11B2, the gene coding for steroid 18-hydroxylase (P-450C18), has been recently shown to be the same gene as that for corticosterone methyl oxidase type I and type II (CMO I & II) which were previously postulated to catalyze the final two steps in the biosynthesis of aldosterone in humans. Molecular genetic analysis of CYP11B2 of three patients affected with CMO I deficiency has revealed that deletion of 5 nucleotides occurs exclusively in exon 1, resulting in a frameshift to form a stop codon in the same exon. Thus, P-450C18 is not produced at all due to the mutation, causing a complete lack of aldosterone biosynthesis in the patients. Restriction fragment length polymorphism analysis has demonstrated that the patients are homozygous and the unaffected parent is heterozygous as for the mutation, indicating that CMO I deficiency is inherited in an autosomal recessive manner. These results provide the molecular genetic basis for the characteristic biochemical phenotype of CMO I deficient patients.

Aldosterone↗
PubMed1993

Dependence of the thymidylate synthase inhibition rate on the interval after the last administration of tegafur in sigmoid colon cancer patients.

The thymidylate synthase (TS) inhibition rate was measured after tegafur (FT) administration (1.5 g/day, at least 10 days) in 7 sigmoid colon cancer patients. The TS inhibition rate decreased as the interval between the time of the last administration and the time of the tumor resection increased longer. This study provides basic data for considering methods of drug administration and assessment of modification, for example, by leucovorin.

Adenocarcinoma↗
PubMed1993

Effect of side-stream cigarette smoke on the hepatic cytochrome P450.

The effect of inhalation of side-stream cigarette smoke on the hepatic microsomal cytochrome P450 was investigated Rats were placed in a chamber of 0.1 m3 in volume, in which cigarettes were burned at the rate of 1, 3, or 5 cigarettes per h, 8 h/day for 5 days. Cytochrome P450 and NADPH-cytochrome c reductase showed no significant changes; however, cytochrome b5 increased significantly. On the other hand, the activity of aryl hydrocarbon hydroxylase (AHH) decreased in the rats treated with a high concentration of cigarette smoke. In order to study the changes of isoforms of cytochrome P450, western blot analyses were performed. The inductions of three kinds of isoforms, cytochromes P450IA1, IA2, and IIB1, were demonstrated immunochemically. However, there were disagreements between the results of the western blot analyses and the measurements of total cytochrome P450 content and AHH activity.

Animals↗
PubMed1993

Personal exposure to nitrogen dioxide from indoor heaters and cooking stoves.

The personal exposure to NO2 generated from various heaters and cooking stoves were studied, using 85 university students. The students attached NO2 filter badges to their chests or collars and wrote down the period of time for heating and cooking for 1 week. Types of heaters and smoking habits were described through a questionnaire. The urinary hydroxyproline/creatinine ratio (HOP/C) was examined as a biomarker for health effects. The outdoor NO2 concentration during the study period was 13.5-13.7 micrograms/m3. Smoking and the usage of electric heaters did not affect the exposure to NO2. Exposure increased according to the length of time kerosene heaters or oil fan heaters were used. The NO2 concentration during the heating by a kerosene heater and an oil fan heater was calculated to be 219 and 474 micrograms/m3, respectively. The correlation between the period of cooking and personal exposure was also observed. The NO2 levels during cooking were calculated to be 290 micrograms/m3. Using these calculated values of NO2 concentration, it is possible to presume the personal exposure levels from the length of time heaters and cooking stoves are used even if the subjects do not attach the filter badges. Neither smoking nor exposure to NO2 were associated with the increase of urinary HOP/C.

Adult↗
PubMed1993

Biological monitoring of toluene and DNA polymorphism in humans.

The effects of genetic polymorphism in aldehyde dehydrogenase 2 (ALDH2) on alcohol intakes and toluene metabolism were studied in workers who handle toluene. The genotypes of ALDH2 were divided into three groups, which were the homozygous genotype of normal ALDH2 (NN), the homozygous genotype of an inactive one (DD) and the heterozygous genotype of normal and inactive ones (ND), using the polymerase chain reaction (PCR) method in a solution containing ddGTP. The alcohol intake of the DD group was very small. On the other hand, the alcohol intake of NN group was higher than that of DD group. That of ND group was about half way between those of NN group and DD group. The alteration of toluene metabolism by the polymorphism of ALDH2 was not clear because the exposure levels of the workers to toluene were low.

Adult↗
PubMed1993

Use of intraoperative mapping to optimize surgical ablation of atrial flutter.

The purpose of this study was to develop a surgical treatment for atrial flutter using intraoperative activation sequence mapping to minimize the surgical procedure necessary to ablate the flutter. A canine model (n = 10) of left atrial enlargement was developed by creating a shunt from the left subclavian artery to the left superior pulmonary vein. Sustained atrial flutter was easily induced in this model. The flutter consisted of a single reentrant circuit that rotated around one or two anatomic obstacles linked by a region of functional block. Epicardial templates, consisting of 252 bipolar electrodes, were used to record activation time maps. After localization of the reentrant circuit, surgical incisions were placed to interrupt the pathways. In all 10 animals, flutter could be induced and intraoperative mapping localized the reentrant circuit. Seven circuits were in the right atrium and three were in the left atrium. The operation ablated all of the preoperative circuits. However, in 5 of the animals, flutter originating from a new circuit could be induced. Activation sequence mapping before and after operation demonstrates that there are multiple potential reentrant pathways in this canine model of atrial flutter. Therefore, all potential pathways must be surgically interrupted to prevent inducibility of atrial flutter.

Animals↗
PubMed1993

Skin barrier defect in atopic dermatitis: increased permeability of the stratum corneum using dimethyl sulfoxide and theophylline.

The existence of a defect in the skin barrier of patients with atopic dermatitis (AD) was demonstrated and its importance in the pathogenesis of AD was emphasized. In order to evaluate the penetration properties of the stratum corneum of AD patients, the in vivo skin response to the penetration of dimethyl sulfoxide (DMSO) and in vitro response to the penetration of theophylline utilizing a diffusion chamber were studied. Both methods demonstrated an increasing level of penetration through the epidermal stratum corneum, with greatest penetration being evident with lesional skin, followed by AD non-lesional and then the normal control. However, statistical significances existed only between non-lesional and lesional skins in the case of the DMSO test, and between the normal control and non-lesional skin in the case of the diffusion chamber analysis using theophylline. Increased penetration of a non-specific nature is important in the pathogenesis of AD.

Adolescent↗
PubMed1993

A study of the growth changes in facial configuration.

In order to explore the growth changes in facial configuration, 160 subjects (80 young adults and 80 children aged 11-12) with normal occlusion were selected for roentgenocephalometric analysis. The present study led to the following conclusions: (a) The ratios of anterior upper to anterior total facial heights, anterior lower to anterior total facial heights, and anterior upper to anterior lower facial heights in both sexes stayed constant around 45, 55, and 81 per cent, respectively. (b) The change in the ratio of the posterior total to anterior total facial heights was mainly due to the greater potentiality of the posterior part of the lower face. (c) The increases of the lower anterior and posterior dental heights were larger than that of the upper anterior and posterior dental heights, respectively. The increases of the upper and lower posterior dental heights were larger than that of the upper and lower anterior dental heights, respectively. (d) On average, the mandibular plane and the occlusal plane tended to rotate forwards with age while the cant of the sella-nasion plane, the Frankfort horizontal plane, and the palatal plane remained fairly unchanged. (e) The saddle angle, the articular angle, and the FNA angle remained relatively stable with age, while the gonial angle and the FNB angle seemed to be age-related. The decrease in the size of the gonial angle might contribute mainly to the flattening tendency of the mandibular growth coincident with general growth. (f) Both the inclination of upper incisor to palatal plane and lower incisor to mandibular plane remained reasonably constant throughout maturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Cell proliferation kinetics of the bile duct epithelium of the rat.

Cell proliferation kinetics of the extrahepatic bile duct were studied by flash and cumulative labelling methods and immunohistochemical techniques. We compared the cell kinetics of the epithelium of the intra- and extra-pancreatic bile ducts and of the bile duct of the ampulla in rats administered intraperitoneally with bromodeoxyuridine (BrdUrd). After a single injection of BrdUrd (flash labelling), labelled cells appeared in the lower portion of the downgrowths of the epithelium in the intra- and extra-pancreatic bile ducts. A gradual accumulation of the labelled cells at the surface epithelium was observed during the cumulative labelling. After cumulative labelling the labelled cells gradually decreased in number and were finally confined to the degenerative cell zone of the surface epithelium 30 days later. Similarly, after a single injection of BrdUrd, the labelled cells in the bile duct of the ampulla appeared at the lower half of the crypt from where they migrated to the upper portion during cumulative labelling. These findings indicate that epithelial cells of the bile duct are renewed at the lower portion of the downgrowths of the epithelium, or crypt, and shed from the surface epithelium or upper portion of the fold. The labelling indices reached 23.83 +/- 7.47% in the intra-pancreatic bile duct, 14.74 +/- 7.99% in the extra-pancreatic bile duct and 43.42 +/- 4.40% in the bile duct of the ampulla at the end of 70 h cumulative labelling. The fluctuating values of the labelling index were higher in the bile duct of the ampulla than in the intra- or extra-pancreatic bile ducts. These results indicate that the bile-duct epithelium undergoes a slower renewal rate than the other parts of the gastrointestinal tract, and that the renewal time of the epithelial cells is shorter at the bile duct of the ampulla than at the intra- or extra-pancreatic bile ducts.

Animals↗
PubMed1993

Simultaneous epicardial and endocardial activation sequence mapping in the isolated canine right atrium.

BACKGROUND: Since the atria are thin-walled structures, most studies that have examined the spread of activation in the atria have assumed that they behave electrophysiologically as a two-dimensional surface. It was the objective of this study to determine whether or not this assumption is true by simultaneously mapping the epicardial and endocardial activation sequences in the right atrium. METHODS AND RESULTS: Identical precisely superpositioned epicardial and endocardial electrode templates with 250 unipolar electrodes each were used to map the isolated canine right atrium (n = 8) during continuous perfusion and superfusion with Krebs-Henseleit buffer. Data were recorded during control conditions (normal sinus rhythm), continuous pacing (S1S1 = 300 msec), and premature stimulation (S1S2 = effective refractory period + 5 msec). Pacing was performed at two sites, one located on the inferior crista terminalis and one lateral to the crista terminalis on a pectinate muscle. Tachyarrhythmias were induced by a single extrastimulus during the continuous perfusion of acetylcholine (10(-3.5) mol/L). Individual electrode sites were correlated with the gross anatomy and histology. Activation time differences were calculated between each two corresponding epicardial and endocardial sites. There were differences in the activation times between the epicardium and endocardium during all experimental conditions. However, the average difference for each condition was < 1 msec, suggesting that overall activation did not spread faster on either the epicardium or the endocardium, even though in certain regions one surface could lead the other. The dispersion of time differences was smallest during normal sinus rhythm and continuous pacing (SD = 5.6-5.8 msec) and largest after premature stimulation (SD = 6.3 msec for crista pacing, p < 0.05; SD = 8.1 msec for pacing lateral to the crista, p < 0.001). Differences in the activation sequence correlated with the underlying anatomic architecture. The largest differences in activation times between the epicardium and endocardium were associated with those regions of the atrium where pectinate muscles ran below the epicardial surface. The pectinate muscles in those areas were often discontinuous with the epicardial surface and facilitated the discordant epicardial-endocardial activation. The discordant activation was also found in regions where the atrial wall thickness was < 0.5 mm and correlated with transmural differences in fiber orientation. A tachyarrhythmia induced in the presence of acetylcholine, which demonstrated a focal activation pattern, was shown to have a reentrant loop that used free-running muscle bundles connecting the epicardial and endocardial surfaces, resulting in a three-dimensional pathway. CONCLUSIONS: The findings of this study demonstrate that epicardial and endocardial activation can be discordant in specific regions and that discordance increases with abnormal activation sequences. Many of the differences in the epicardial and endocardial activation can be correlated with the heterogeneity of the anatomic architecture of the right atrium. The study also demonstrates that reentry can occur in a three-dimensional plane using the epicardial and endocardial surfaces connected by transmural muscle fibers.

Animals↗
PubMed1993

A nonsense mutation (TGG [Trp116]-->TAG [Stop]) in CYP11B1 causes steroid 11 beta-hydroxylase deficiency.

Steroid 11 beta-hydroxylase deficiency (11 beta OHD), an autosomal recessive hereditary disease, accounts for 5-8% of cases of congenital adrenal hyperplasia. In this study, we carried out a molecular genetic analysis of CYP11B1 encoding steroid 11 beta-hydroxylase (P450c11) from a Japanese patient affected with this disease. Nucleotide sequence analysis of polymerase chain reaction-amplified products of the patient's genome revealed the occurrence of a stop codon in exon 2 due to a point mutation, TGG-->TAG (Trp116-->Stop). To further analyze the role of CYP11B2 encoding steroid 18-hydroxylase (P450c18) in the 11 beta OHD patient, CYP11B2 of the patient was also amplified and sequenced. In contrast to CYP11B1, there was no mutation in CYP11B2. Restriction fragment length polymorphism analysis indicated that the 11 beta OHD patient is homozygous and his unaffected parents are heterozygous for the mutation. When a cDNA corresponding to CYP11B1 of the 11 beta OHD patient was transfected into COS-7 cells, steroid 11 beta-hydroxylase activity was not detectable in mitochondria of the cells. These results demonstrate that intact P450c11 was not produced at all due to the nonsense mutation in CYP11B1 of the patient without any mutation in CYP11B2.

Adrenal Hyperplasia, Congenital↗
PubMed1993

Marked species-difference in the vascular angiotensin II-forming pathways: humans versus rodents.

Using isolated arteries, we demonstrated a marked difference in the angiotensin II-forming systems between human and rodent vessels. In human arteries, only 30-40% of the conversion of angiotensin I to angiotensin II depended on the angiotensin-converting enzyme (ACE), and the rest of the angiotensin II formation was ascribed to chymostatin-sensitive angiotensin II-generating enzyme (CAGE). On the contrary, angiotensin II formation in rodent arteries totally depended upon ACE, without any sign of CAGE involvement. Such a marked species-difference can be relevant to the reported difference between humans and rodents in the ACE inhibitor effects on the myointimal hyperplasia after intimal balloon injury.

Adult↗