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T Kawamoto

Publications and source records attributed to T Kawamoto.

At least 19 recordsLinked to original sources
PubMed1992

The chimeric gene linked to glucocorticoid-suppressible hyperaldosteronism encodes a fused P-450 protein possessing aldosterone synthase activity.

Glucocorticoid-suppressible hyperaldosteronism (GSH) is one variety of primary aldosteronism with hypertension and is inherited in an autosomal dominant mode. A recent report has indicated that GSH is caused by a gene duplication arising from unequal crossing over between the two genes, CYP11B1 and CYP11B2, encoding P-450(11 beta) and P-450C18, respectively (Lifton et al. Nature (1992) 355, 262-265). The nucleotide sequence analysis in the present study has demonstrated that unequal crossing over in the chimeric gene formed by the gene duplication occurs within the region from the 3'-portion of exon 4 through the 5'-portion of intron 4 in Australian GSH patients. Namely, the chimeric gene encodes a fused P-450 protein consisting of the amino-terminal side of P-450(11 beta) (encoded by exons 1-4 of CYP11B1) and the carboxyl-terminal side of P-450C18 (encoded by exons 5-9 of CYP11B2). When a cDNA corresponding to the chimeric gene is transfected into COS-7 cells, the fused P-450 protein expressed in the mitochondria exhibits steroid 18-hydroxylase or aldosterone synthase activity. These results provide the molecular genetic basis for the characteristic biochemical phenotype of GSH patients.

Animals↗
PubMed1992

The effect of ethylene glycol monomethyl ether and diethylene glycol monomethyl ether on hepatic gamma-glutamyl transpeptidase.

In this paper, we determined whether ethylene glycol monomethyl ether (EGME) and diethylene glycol monomethyl ether (diEGME) induce hepatic gamma-glutamyl transpeptidase activity. Male adult Wistar rats weighing 220 g were used as experimental animals. EGME (100, 300 mg/kg per day) and diEGME (500, 1000, 2000 mg/kg per day) were administered by gavage for 1, 2 or 5 days or 4 weeks. In the 4-week study, experimental animals were administered EGME or diEGME once a day orally, 5 days/week. EGME treatment increased the serum gamma-glutamyl transpeptidase (GGT) level significantly, however, diEGME did not. The activities of three other enzymes (SGOT, SGPT and ALP) in serum were not altered by EGME or diEGME treatment and thus there was no biochemical indices of hepatic damage by EGME or diEGME. EGME treatment increased the GGT activities in the liver and lungs. Of the organs examined, the induction of GGT was the greatest in the liver. The inducibility in the liver was 216% for the 5-day treatment and 460% for the 4-week treatment. A dose-dependent increase of hepatic microsomal GGT activity by EGME was observed. On the other hand, renal GGT activities were declined to 72% and 60% of control by the 5-day and 4-week EGME treatments, respectively. DiEGME did not affect the GGT activities in any of the tissues except those of the brain. In the histochemical study, most hepatocytes at the periportal zones were stained with GGT staining after the 4-week treatment. However, the hepatocytes at the central zones were negative.

Animals↗
PubMed1992

Characterization of a cis-acting regulatory element involved in human-aromatase P-450 gene expression.

The characteristics of a cis-acting regulatory region involved in the human-aromatase P-450 gene have been examined by transient expression analysis. The region spans from -242 - -166 relative to the cap site of the gene. A fragment containing the region excised from the gene enhances heterologous promoter activity as well as its own promoter activity in a position-independent and orientation-independent manner. The fragment exerts its enhancer activity in human BeWo choriocarcinoma cells in which the aromatase P-450 gene is expressed, but not in other cell lines tested. Deletion of 38 bp from the 3' end of the fragment results in a complete loss of enhancer activity. A gel-retardation assay with nuclear extracts from BeWo cells suggests the existence of a nuclear factor(s) which interacts with the fragment. These results suggest that the regulatory element in the fragment is involved in efficient transcription of the human-aromatase P-450 gene.

Animals↗
PubMed1992

Role of steroid 11 beta-hydroxylase and steroid 18-hydroxylase in the biosynthesis of glucocorticoids and mineralocorticoids in humans.

A gene encoding steroid 18-hydroxylase (P-450C18) was isolated from a human genomic DNA library. It was identified as CYP11B2, which was previously postulated to be a pseudogene or a less active gene closely related to CYP11B1, the gene encoding steroid 11 beta-hydroxylase (P-45011 beta) [Mornet, E., Dupont, J., Vitek, A. & White, P. C. (1989) J. Biol. Chem. 264, 20961-20967]. The nucleotide sequence of the promoter region of the P-450C18 gene is strikingly different from that of the P-45011 beta gene, although the sequences of their exons are 93% identical. The transient expression in Y-1 adrenal tumor cells of CAT constructs with a series of deletion mutants of promoter regions of both genes indicated that the two genes are regulated differently. P-450C18 as expressed in COS-7 cells exhibits steroid 18-hydroxylase activity to catalyze the synthesis of aldosterone and 18-oxocortisol and exhibits steroid 11 beta-hydroxylase activity as well. In contrast, P-45011 beta as expressed in the cultured cells exhibits steroid 11 beta-hydroxylase activity exclusively but fails to catalyze the synthesis of aldosterone and 18-oxocortisol. These results indicate that P-45011 beta and P-450C18 are products of two different genes and that the former participates in the synthesis of glucocorticoids whereas the latter participates in the synthesis of mineralocorticoids in humans.

Amino Acid Sequence↗
PubMed1992

Congenitally defective aldosterone biosynthesis in humans: the involvement of point mutations of the P-450C18 gene (CYP11B2) in CMO II deficient patients.

The gene for steroid 18-hydroxylase (P-450C18) has been recently assigned to encode corticosterone methyl oxidases Type I and Type II which were previously postulated to catalyze the final two steps in the biosynthesis of aldosterone in humans. Molecular genetic analysis of the P-450C18 gene is three patients from three different families affected with CMO II deficiency has indicated that a point mutation of CGG----TGG (181Arg----Trp) in exon 3 and one of GTG----GCG (386Val----Ala) in exon 7 occur exclusively in the gene of the patients. Analysis of PCR products by restriction enzymes (HapII and HphI) has indicated that the patients are homozygous and the unaffected parent is heterozygous for both mutations, in accordance with the established concept that CMO II deficiency is inherited in an autosomal recessive manner. These data clearly provide the molecular genetic basis for the characteristic biochemical phenotype of CMO II clinical variants.

Aldosterone↗
PubMed1992

Kinetic resolution of organosilicon compounds by stereoselective dehydrogenation with horse liver alcohol dehydrogenase.

Stereoselective dehydrogenation of three isomers of trimethylsilylpropanol was carried out with horse liver alcohol dehydrogenase (HLADH, EC 1.1.1.1.) and optically active organosilicon compounds were obtained in a water-organic solvent two-layer system with coenzyme regeneration. Furthermore, we examined the effects of the silicon atom on stereoselectivity of HLADH compared to the corresponding carbon compounds. Substitution of the silicon atom for the carbon atom was found to improve the stereoselectivity of HLADH. For example, the optical purity of the remaining 1-trimethylsilyl-2-propanol was higher than 99% enantiomeric excess (ee) at 50% conversion, whereas that of the carbon analogue was 84% ee. This phenomenon was probably ascribable to the bulkiness of the organosilicon compounds derived from their longer Si-C bond. Kinetic analysis in an aqueous monolayer system demonstrated that the specific properties of the silicon atom greatly affected the reactivity of these substrate compounds.

1-Propanol↗
PubMed1992

Craniofacial pattern of Class III deciduous dentition.

The purpose of this study was to investigate the morphological characteristics of the cranio-dento-facial complex of children with deciduous dentition and Class III malocclusion. Forty Chinese children in Taiwan with normal occlusion and 40 with Class III malocclusion in deciduous dentition were selected for cephalometric analysis. Mandibular length was significantly greater and the mandible was situated farther forward in the Class III group. The maxilla was also slightly backward in this group, perhaps in association with the shorter maxillary length. The mandibular incisors were tipped lingually to compensate for the intermaxillary skeletal dysplasia and the maxillary incisors were tipped lingually by the retroinclined mandibular incisors.

Cephalometry↗
PubMed1992

[Application of visual analogue scale of happiness to elderly Himalayan highlanders].

Visual analogue scale of happiness (VAS-H) was applied to elderly Himalayan highlanders to investigate the influence of life-style and socio-cultural background on subjective happiness. The score of "VAS-H" and neuropsychological function tests in 733 Himalayan highlanders who belonged to 5 separate villages were compared with those in 313 Japanese elderly subjects. The places of study consisted of 4 villages (Khalimabad; K, Gulmit; G, Pasu; P, Shimshal; S) in Hunza area in Pakistan, and Namche Bazar; N in Nepal. Degree of modern civilization was highest in K, followed by N, G, P and lowest was that in S by historical and sociological aspects. The mean VAS-H sore in Himalayan highlanders and the degree of modern civilization in the area was in inverse proportion. Himalayan elderly women showed a significant lower score on VAS-H compared with elderly Himalayan men or elderly Japanese subjects. The VAS-H score in the Japanese elderly correlated significantly with the stability of posture and walk, and that of Himalayan highlanders correlated significantly with manual skill. In conclusion, the life style or socio-cultural background strongly affected subjective happiness in the elderly. The VAS-H was useful in comparing subjective happiness in different cultures.

Adult↗
PubMed1992

[Anatomical observations on the attachment of human temporalis and masseter muscles].

It is very important for orthodontics to investigate the bone remodeling pattern in the area of the attachment of the masticatory muscles induced by the changing muscular function. In the present study, the insertion pattern of Sharpey's fibers and the bone structure are comparatively studied on the temporalis and the masseter muscles macroscopically, light microscopically and electron microscopically, respectively. The following results are obtained: 1) The periosteum on the squamous part of the temporal bone is thinner, while the one on the lower ridge of the zygomatic arch is relatively thicker. 2) The fine and loose Sharpey's fibers are found mostly on the squamous part of the temporal bone, while the ones on the lower ridge of the zygomatic arch are relatively coarse and dense. 3) Comparing with the squamous part of the temporal bone, the fibrous bone is thinner and also few reversal lines and resting lines are observed at the lower ridge of the zygomatic arch. These findings seem to prove the fact that the bone remodeling proceeds frequently within the limited narrow area. These differences are directly due to the differences of the anatomical site and the muscular function.

Aged↗
PubMed1992

[Pulsed Doppler echocardiographic observation of left ventricular filling dynamics after aortic valve replacement in patients with chronic aortic regurgitation].

The 23 patients who underwent aortic valve replacement (AVR) for aortic regurgitation (AR) from 1977 to 1990 were studied with pulsed Doppler echocardiography. The patients were divided into two groups. The A group consisted of 5 patients whose end-systolic volume index (ESVI) were more than 200 ml/m2 and/or left ventricular ejection fraction (EF) were less than 0.35 before AVR. The B group consisted of 18 patients whose ESVI were less than 200 ml/m2 and EF were more than 0.35 before AVR. A Doppler volume sampler was placed at the center of mitral orifice to measure the transmitral inflow velocity after AVR (mean 28 months). Left ventricular filling dynamics were assessed by the peak velocity in the rapid filling phase (R), the peak velocity in the atrial contraction phase (A) and the ratio of A by R (A/R ratio) of mitral flow velocity pattern. The deceleration rate of early diastolic rapid inflow (DeR) determined as the slope a straight line drawn between the peak of early diastolic inflow and a point at half peak velocity on the fall side of the envelope. Result was as follows; 1) The DeR showed significant correlation with the EF (r = 0.56, p < 0.01). The DeR showed significant inverse correlation with the ESVI (r = -0.52, p < 0.05). 2) The R velocity (mean 43.9 +/- 7.9 cm/sec) in group A was significantly lower than in group B (mean 61.4 +/- 18.6 cm/sec), (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[The pulmonary venous obstruction following repair with absorbable sutures in total anomalous pulmonary venous drainage--a case report].

A 4-month-old boy with infracardiac type of total anomalous pulmonary venous drainage (TAPVD) who underwent anastomosis between left atrium and common pulmonary vein at age of one month with absorbable suture of polydioxanone (PDS), was suffered from pulmonary venous obstruction (PVO). The ostia of pulmonary veins were stenosed severely. The histological findings showed that there were inflammatory changes and fibrosis around PDS suture. These findings suggested that PDS would cause inflammatory change of tissues around, which might be occurred following repair of TAPVD.

Anastomosis, Surgical↗
PubMed1991

Absorption of cadmium after a long-term oral administration of cadmium to dogs.

A long-term experiment using beagle dogs to investigate the absorption of cadmium was conducted. The dogs in the experimental groups were given a commercial diet and pelleted food containing 1, 3, 10, 50, and 100 mg of cadmium per day. The cadmium concentration in the blood increased continuously, gradually reaching a steady state following the administration of cadmium. The cadmium excreted daily in urine increased continuously. The cumulative excreted amount of cadmium in urine was calculated by using the trapezoidal rule based on the data of excretion of cadmium in urine. Then the absorbed fraction of administered cadmium was estimated on the basis of the relationship between the cumulative excreted amount of cadmium in urine and the cumulative administered dose of cadmium after the cadmium concentration in blood reached a steady state. The absorbed fraction of cadmium decreased with an increase in the administered dose of cadmium. A dose-dependent increase between the absorbed amount and the administered dose was observed.

Administration, Oral↗
PubMed1991

Toxic effects of ingested lead shots in domestic fowls.

Lead poisoning from ingested shots is thought to be a major cause of high mortality in waterfowls throughout the world, and some millions of fowls die each year. However, there have been no other Japanese studies regarding lead toxicity in birds from ingested lead shots. We used domestic fowls instead of waterfowls as the experimental birds, in order to make clear the distribution and the toxic effects of lead shot in the birds. In a 1-wk follow-up study, two, four, and eight #4 lead shots were administered orally. A dose-dependent increase of the lead concentrations in blood, brain, liver, kidney, lung, spleen, bone, and epidermis of the gizzard was observed. In the 12-wk follow-up study, twenty domestic fowls were used and eight #4 lead shots were administered to the experimental birds. Lead concentrations in brain, liver, kidney, bone, ovary, fat tissue, and breast muscle increased more than in the 1-wk follow-up study. The observed lead concentrations of organs in the domestic fowls were lower than those of the other species used in past studies. The blood lead concentrations increased up to the third week and a remarkable suppression of delta-aminolevulinic acid dehydratase activity in red blood cells and elevation of free erythropoietic protoporphyrin were observed in the exposed group. Body weight loss, loss of hair, and neurological symptoms were also observed. However, there were no mortalities during the 1- and 12-wk studies.

Administration, Oral↗
PubMed1991

Isolation of a full-length cDNA encoding mouse aromatase P450.

A full-length cDNA clone for aromatase P450 has been isolated from a pregnant mouse ovarian cDNA library. The insert of this clone (2394 bp) contains a 1509-bp open reading frame encoding 503 amino acid residues together with a 46-bp 5'-untranslated stretch and an 839-bp 3'-untranslated region to which a poly(A) tract is attached. Northern blot analysis of ovarian RNA from pregnant mice reveals a major mRNA band of 2.5 kb with a minor band of 2.1 kb. Comparison of mouse aromatase P450 with that of rat, human, and chicken shows 91, 81, and 69% identity in the nucleotide sequence and 92, 79, and 69% identity in the deduced amino acid sequence, respectively. The membrane-spanning domain of mouse aromatase P450 is estimated to be an extremely hydrophobic segment located within the N-terminal region of the molecule. Furthermore, a highly conserved heme-binding domain is noticed.

Amino Acid Sequence↗
PubMed1991

Selective depletion of immature thymocytes by oral administration of ethylene glycol monomethyl ether.

Although immunotoxicity of ethylene glycol monomethyl ether (EGME) has been strongly suspected, functional evaluation of the immune response in EGME-treated animals was negative in previous studies. We observed a decrease in thymic cellularity and increases in the various ex vivo immunological assays in mice, orally administered with EGME 0.5 or 1.0 mg/g body weight daily for 5 or 10 days: ex vivo lymphoproliferative responses to concanavalin A, in vitro induction of trinitrophenyl (TNP)-specific cytotoxic T-cell activity of thymocytes and splenocytes. Histopathological examination of the thymus of the treated mice disclosed a markedly atrophic cortex and almost intact thymic medulla. Study of thymocyte surface markers revealed that CD4+/CD8+, Thy-1+, PNA+ immature thymocytes were relatively decreased in EGME-gavaged mice and that, thus, ratios of CD4-/CD8+, H2+ mature thymocytes were enriched. These findings indicate that oral administrations of EGME selectively deplete immature thymocytes in mice. Although the mechanism of action remains unknown, the EGME-induced immature thymocyte depletion is not considered to be due to lymphocidal action of corticosteroids.

Administration, Oral↗
PubMed1991

Expression of c-erbB-2 gene product in urinary bladder cancer.

Expression of the c-erbB-2 gene product and the epidermal growth factor receptor (EGF-R) was investigated in 54 cases of human bladder cancer immunohistologically and by Western blot analysis. For detection of the c-erbB-2 product, two specific antibodies, a rabbit polyclonal antibody directed to the intracellular domain and a murine monoclonal antibody recognizing an epitope in the extracellular domain, were used. Seventeen cases of bladder cancer were stained by the anti-c-erbB-2 polyclonal antibody, while 20 cases were stained by the monoclonal antibody, with good correlation on both stainings (p less than 0.01). There were four c-erbB-2 positive cases in 26 G1 tumors, four in 15 G2 tumors, and nine in 13 G3 tumors. There were also eight erbB-2 positive cases in nine muscle-invasive tumors, nine of 45 superficial tumors, four of five with lymph node metastasis, and seven of 14 without metastasis, as revealed by staining with the polyclonal antibody. Thus, the c-erbB-2 gene product was more frequently expressed in high grade tumors (p less than 0.01), in high stage tumors (p less than 0.01), and nodal metastatic tumors (N.S. by Chi-square test). Twenty-two of the 54 tumors were stained by an anti-EGF-R monoclonal antibody, 528 IgG. The expression of EGF-R was independent of histological grading, tumor stage, and nodal status, and no correlation was observed between expression of the c-erbB-2 product and EGF-R. The c-erbB-2 product may be applicable as a tumor marker for evaluation of malignant potential, invasiveness, and probably metastatic potential of human bladder cancer.

Antibodies, Monoclonal↗
PubMed1991

Quantitative assay of epidermal growth factor receptor in human squamous cell carcinomas of the oral region by an avidin-biotin method.

A quantitative assay method for epidermal growth factor receptors (EGFRs) of human tumor tissues was established, based on enzyme-labeled avidin-biotin (LAB) interaction with anti-human EGFR monoclonal antibody 528IgG. A standard calibration curve for EGFR estimation in human tumor tissues was obtained with A431#8 cells cloned from A431 human epidermoid carcinoma cell line. The coefficient of variance for the standard curve was below 35% in the application to tumor tissues from nude mice implanted with human tumor cell lines. The minimum tissue amount required for the quantitative assay was around 0.1 g (wet weight). Using the LAB method, the correlation between the level of EGFR number and tumor malignancy was examined for 14 human squamous cell carcinomas (SCCs) from the oral region. Seven of the SCCs showed a more than two-fold higher EGFR number compared to normal gingival tissues. Three highly aggressive carcinomas with poor prognosis possessed five to ten times higher levels of EGFR number than normal tissues. The elevated EGFR level in the SCCs seems to correlate to increasing tumor size and the stage of SCCs as clinically classified according to the 1987 UICC TNM system.

Adult↗