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T Kawamoto

Publications and source records attributed to T Kawamoto.

At least 199 records · Page 11Linked to original sources
PubMed1993

In vitro pharmacology of a novel non-peptide angiotensin II-receptor antagonist, E4177.

E4177, 3-[(2'-carboxybiphenyl-4-yl)methyl]-2-cyclopropyl-7-methyl-3H- imidazo[4,5-b]pyridine, was characterized by in vitro autoradiography and by examining functional antagonism upon angiotensin II (Ang II)-induced contraction of isolated vessels. In rat adrenal cortex and liver, E4177 competitively inhibited the specific binding of 125I-[Sar1,Ile8]Ang II, with IC50 being (5.2 +/- 1.0) x 10(-8) M for the adrenal cortex and (1.2 +/- 0.3) x 10(-7) M for the liver. These IC50 values were similar to those for losartan, which showed an IC50 of (6.0 +/- 0.9) x 10(-8) M for the adrenal cortex and (1.3 +/- 0.5) x 10(-7) M for the liver. In contrast, E4177 and losartan had little effect on the binding to rat adrenal medulla where AT2-receptors predominate. These results indicate that E4177 is AT1-specific as is losartan. E4177 and losartan competitively antagonized the Ang II-induced contraction of human and rabbit arterial strips without any agonistic action. The obtained IC50 values indicated that E4177 was twice as potent as losartan in human arteries and three times more so in rabbit aortic strips. Responses to norepinephrine, serotonin, histamine or KCl were not affected by E4177. In addition, E4177 (10(-5) M) had no effect on angiotensin-converting enzyme activity. These data indicate that E4177 is a potent AT1 Ang II-receptor antagonist that may be clinically useful for the treatment of cardiovascular diseases such as hypertension.

Adrenal Cortex↗
PubMed1993

[Immunohistochemical detection of proliferating cell nuclear antigen (PCNA) in carcinoma at the confluence of the main hepatic ducts and its relationship to expression of CEA, CA19-9 and EGF receptor].

The Distribution pattern and proportion of the positive cells of proliferating cell nuclear antigen (PCNA) were examined immunohistochemically to study the proliferative activities of 33 cases of carcinoma found at the confluence of the main hepatic ducts. Expressions of CEA, CA19-9 and EGF receptor (R) were further examined with serial histological sections and comparatively analyzed with the result of PCNA staining and the clinico-pathological features of the carcinoma. PCNA positive cancer cells were observed in greatest abundance at the deeply infiltrated region of the carcinoma. CEA and CA19-9 were also expressed most strongly in this region and a stromal staining pattern was predominant. However, negative or apical staining patterns of CEA and CA19-9 were more frequent in the surface or the lateral spreading regions of the carcinoma, where the PCNA positive cancer cells were fewer in number. EGFR expression was rarely observed in the present study.

Adenocarcinoma↗
PubMed1993

Long-term survivors after salvage surgery combined with radiotherapy for recurrence of stage IV main hepatic duct cancer--report of two cases.

Main hepatic duct cancer is notorious for its poor prognosis and frequent locoregional failure of therapy even after curative resection. In this paper, two cases of recurrent carcinoma of the stage IVA main hepatic duct are presented. One patient had local failure 13 years after curative resection of the tumor and the other had regional failure 18 months after combination treatment with non-curative resection and intra-operative radiation therapy. Recurrent tumors were successfully treated with combined resection and postoperative radiation therapy or with combined intra-operative radiation therapy and postoperative radiation therapy. The patients are well 16.9 and 6.3 years, respectively, after primary tumor resection. We briefly review a number of other reports of salvage treatment in patients with recurrent carcinoma of the main hepatic ducts and discuss the results with particular reference to the advantage of salvage therapy for the main hepatic duct cancer.

Adenocarcinoma↗
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↗