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Biomedical subjects

M Sakamoto

Publications and source records attributed to M Sakamoto.

At least 379 records · Page 21Linked to original sources
PubMed1995

Induction of metallothionein by thrombin in cultured vascular endothelial and smooth muscle cells.

Metallothionein induction by thrombin was investigated using a culture system of vascular endothelial and smooth muscle cells. It was found that the protease induced metallothionein in endothelial cells derived from human aorta and umbilical vein as well as bovine aorta in a concentration-dependent manner. Thrombin also induced metallothionein in vascular smooth muscle cells derived from bovine aorta but not in cells derived from human, rabbit and rat aortas. In bovine aortic endothelial and smooth muscle cells, induction of metallothionein by thrombin was unaffected by the protein kinase C inhibitor staurosporine; in addition, a protein kinase C activator, phorbol 12-myristate 13-acetate, failed to induce metallothionein, suggesting that the induction by thrombin occurred through pathway(s) other than protein kinase C activation. It is suggested that metallothionein may be induced during hemostasis in the vascular tissue through protein kinase C-independent pathway(s).

Animals↗
PubMed1995

Vascular smooth muscle cells in culture are highly sensitive to cadmium cytotoxicity without species-related differences: comparison with Chang liver cells.

Human, rabbit and rat aortic smooth muscle cells (hSMC, rSMC and A10 cells, respectively) were cultured with cadmium chloride and compared with human Chang liver cells to characterize the response of vascular smooth muscle cells to the metal. It was revealed that all tested vascular smooth muscle cells were markedly more sensitive to cadmium cytotoxicity than Chang liver cells. Cadmium accumulated more markedly in vascular smooth muscle cells than in Chang liver cells. After exposure to cadmium, metallothionein was induced in a concentration-dependent manner in Chang liver cells, it was constitutively high in hSMC, sensitively induced in rSMC and was constitutively low and induced within narrow limits in A10 cells. The intracellular content of reduced glutathione was greater and significantly enhanced by cadmium only in A10 cells. The present data suggest that vascular smooth muscle cells are, in general, sensitive to cadmium cytotoxicity without any species-related differences, mainly due to a higher accumulation of the metal within cells.

Animals↗
PubMed1995

Enantioselective biotransformation of 1-isopropylnaphthalene in rabbits.

1-Isopropylnaphthalene (1) was administered orally to rabbits and the following eight metabolites, 2-(1-naphthyl)-2-propanol (7), 2-(1-naphthyl)-1-propanol (8: R/S = 83:17), 2-(1-naphthyl)-1,2-propanediol (9:R/S = 40:60), 4-isopropyl-1,2-naphthoquinone (10), 4-isopropyl-1-naphthol (11), 4-isopropyl-2-naphthol (12), 5-isopropyl-2-naphthol (13), and 2-(1-naphthyl)propanoic acid (14') as its methyl ester (14: R/S = 52:48), were isolated from urine. Among them, three metabolites (8, 9, and 14), possessing an asymmetric carbon atom in the molecule, were formed enantioselectively and five metabolites (7, 10, 11, 12, and 13) were formed regioselectively. The presumed metabolic pathways of 1-isopropylnaphthalene (1) in rabbits leading to these metabolites are discussed.

Administration, Oral↗
PubMed1995

Longitudinal investigation of epidemiologic feature of adenovirus infections in acute respiratory illnesses among children in Yamagata, Japan (1986-1991).

Using human embryonic fibroblast (HEF) and HEp-2 cell cultures, adenoviruses were isolated from 989 (3.7%) out of 26,793 pediatric patients with ARI in Yamagata, Japan from January, 1986 to December, 1991. All isolates were identified as types 1 (Ad1)-6 and no other serotypes were identified. Epidemiologic feature was different depending on the subgenus group. Ad1, 2, 5 and 6 (group C) were endemic and the infections occurred frequently in the summer season. Ad3 (group B) was epidemic in the autumn to winter season, although the virus was isolated every month in non-epidemic season. No seasonal distribution of Ad4 (group E) could be determined because the number of patients was limited. Neutralizing antibody positive ratio for group C were more than 40% at 1-2 years of age and almost 100% by 10 years of age but those for Ad3 (group B) were 40% by 10 years of age. The neutralizing antibodies for Ad4 (group E) or Ad7 (group B) became negative by 10 years of age. With group C infections, most cases were infants and young children less than 2 years of age, but Ad3 infections were older children with the peak at 4 and 5 years of age.

Acute Disease↗
PubMed1995

Effects of the neonatal vitamin A exposure on behaviors of adult rats.

The effects of neonatal vitamin A exposure on six behavioral parameters in adult Wistar rats were investigated. Newborn male rats were injected intraperitoneally with 80,000 IU/kg/day of retinol palmitate (vitamin A) dissolved in physiological saline or vehicle alone (controls) during 1-5 days after birth. The animals were examined using the open field test (at 36 weeks of age), the rotarod test (38 weeks), the Biel water-maze test (40 weeks), the conditioned avoidance test (42 weeks), the running-wheel activity with pentobarbital challenge test (44 weeks), and the tail flick test (45 weeks). The vitamin A-exposed rats made significantly more errors and took significantly longer times in the Biel water-maze test, and showed significantly slower responses in the tail flick test than the controls. No significant effects of treatment with vitamin A were observed in any of the other behavioral tests. These results indicate that a long-lasting defect in learning in water-maze task and depression of the heat-pain response are induced in rats exposed neonatally to vitamin A.

Animals↗
PubMed1995

CT diagnosis of early hepatocellular carcinoma: sensitivity, findings, and CT-pathologic correlation.

OBJECTIVE: The purpose of this study was to determine the sensitivity of CT in detecting early hepatocellular carcinoma and to evaluate its CT appearance. An early hepatocellular carcinoma is a nodular lesion with no fibrous capsule composed of well-differentiated tumor histologically. It differs from a small hepatocellular carcinoma, which is an overt tumor that is moderately to poorly differentiated and has a fibrous capsule. Size is not a criterion for distinguishing between early and small hepatocellular carcinomas. MATERIALS AND METHODS: Thirty-one patients with 39 histopathologically proved early hepatocellular carcinomas (mean diameter, 1.7 cm) found by sonography, MR imaging, and/or intraoperative sonography were included in a retrospective study. We reviewed unenhanced CT scans of the entire liver in 30 patients (37 lesions) and early and late (35 sec and 5 min after the beginning of injection of contrast material) contrast-enhanced CT scans of the entire liver in all 31 patients (table incremental CT in 21; helical CT in 10; 39 lesions). Eighteen histologically proved small hepatocellular carcinomas (< or = 3 cm; mean diameter, 2.3 cm), present in the same patients, served for comparison. Histopathologically, nine patients had chronic hepatitis, and 22 had cirrhosis. RESULTS: The overall sensitivity of CT in detecting early hepatocellular carcinoma was 56%. These tumors were usually isodense with respect to surrounding liver on unenhanced, early enhanced, and late enhanced CT scans (iso-iso-iso). This pattern was seen in 17 (46%) of 37 lesions; thus, these 17 histologically proved early hepatocellular carcinomas were not detected with CT. An iso-iso-low density pattern was recognized in eight (22%), a low-low-low pattern in seven (19%), and several different patterns in five (13%) of the 37 lesions. Only two (5%) of 39 early hepatocellular carcinomas had a high-density appearance on early enhanced CT scans. In comparison, the most common pattern of small overt hepatocellular carcinomas on CT scans was low-high-low, seen in 17 lesions (94%) detected with CT. When the density of lesions on unenhanced CT scans was compared with the histopathologic appearance of the masses, low-density lesions showed mild to moderate fatty change and isodense lesions showed no or minimal fatty change (p = .006). CONCLUSION: The sensitivity of CT in detecting early hepatocellular carcinoma is poor (56%). However, the diagnosis of early hepatocellular carcinoma should be considered if CT scans show a small lesion with an iso-low or low-low density enhancement pattern on early and late contrast-enhanced CT scans, respectively, in patients with chronic liver disease.

Aged↗
PubMed1995

[Predicting renal stone fragility against ESWL].

BACKGROUND: The mineral content (MC) and mineral density (MD) of renal stones, measured by dual energy X-ray absorptiometry, were compared with the experimental and clinical results of stone disintegration by shock wave. METHODS AND RESULTS: In the experimental study, the MC and MD values correlated significantly with the total shock wave energy used, with a correlation coefficient (r) for MC being 0.814 and for MD, 0.706 (n = 46). The mean MC and MD values were 0.521 +/- 0.387g and 0.317 +/- 0.121 g/cm2 (n = 14) respectively in patients undergoing clinically successful ESWL, while those were 4.27 +/- 6.19g and 0.626 +/- 0.302 g/cm2 (n = 6) respectively in patients undergoing clinically unsuccessful ESWL. Those values differed significantly between the two groups (p < 0.05, p < 0.01, respectively). The combination of MC, MD and area values of a stone was shown to be the best predictor of treatment outcome, with a predictive value of incorrect discrimination being 17% and that of correct discrimination, 85% using linear discriminant analysis. CONCLUSION: The mineral content and mineral density, measured by dual energy X-ray absorptiometry, may provide the best prediction of outcome of patients undergoing ESWL treatment.

Absorptiometry, Photon↗
PubMed1995

Two distinct patterns of peritoneal involvement shown by in vitro and in vivo ovarian cancer dissemination models.

We established an in vitro peritoneal dissemination model using six ovarian cancer cell lines and cultured mesothelial cells. Ovarian cancer cells were classified into two types, invasive or adhesive, on the basis of their interaction with the mesothelial cell monolayer. The ovarian cancer cell lines derived from mucinous cystadenocarcinoma, poorly differentiated adenocarcinoma and undifferentiated carcinoma, which belonged to the invasive type, began to invade beneath the mesothelial monolayer from several hours after seeding in vitro, expelling the mesothelial cells at the periphery and forming colonies directly on the dish surface. On the other hand, cancer cell lines of clear cell carcinoma, which belonged to the adhesive type, showed colony formation with adhesion on the mesothelial monolayer even 18 h after seeding. Invasive-type cell lines invaded into the mesothelial monolayer at various rates in vitro, and the degree of invasiveness showed good correlation with the degree of peritoneal dissemination in vivo after intraperitoneal injection of cancer cells into nude mice. Adhesive-type cells showed rather higher dissemination rates in vivo. Microscopic observation of in vivo peritoneal dissemination at one day after inoculation also revealed two patterns of peritoneal involvement similar to those in vitro. In the in vitro model, anti-integrin alpha 2- and beta 1-antibodies inhibited the infiltration of invasive-type cells into the mesothelial monolayer, but did not affect colony formation by adhesive-type cells on the monolayer, indicating that invasion by both cell types was mediated by different molecules. This in vitro model is thought to be useful for analysis of the molecular mechanisms of peritoneal dissemination.

Animals↗
PubMed1995

Antioxidant effects of "beta catechin".

The free radical scavenging effect of "beta catechin", an antioxidant preparation containing green tea extract, ascorbic acid, sunflower seed extract, dunaliella carotene and natural vitamin E, was evaluated. Two techniques were used: electron spin resonance (ESR) spectrometry to measure radical-scavenging activity, and measurement of its effect on iron-induced lipid peroxidation in brain. A 0.05% solution of "beta catechin" completely scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals (6.1 x 10(15)spins/ml). A 10% solution of "beta catechin" completely scavenged superoxide (4.2 x 10(15) spins/ml) generated by the hypoxanthine-xanthine oxidase system. An undiluted solution of "beta catechin" scavenged about 90% of hydroxyl radicals (3.5 x 10(15) spins/ml) generated by the Fenton reaction. "beta catechin"s effect on the accumulation of thiobarbituric acid-reactive substances (TBARS) was evaluated from tissue obtained from the ipsilateral cortex of FeCl3-induced epileptic rats. Oral administration of "beta catechin" (1 or 2ml/kg body weight) both inhibited TBARS formation and increased the activity of superoxide dismutase (SOD) in the ipsilateral cortex 30 min after iron-salt injection into the left sensory motor cortex. These data suggest that "beta catechin" has an antioxidant effect and may have a prophylactic effect against aging and other neurological diseases related to free radical mechanisms.

Animals↗
PubMed1995

Oral administration of clotrimazole and blockade of human erythrocyte Ca(++)-activated K+ channel: the imidazole ring is not required for inhibitory activity.

The Ca(++)-activated K+ (Gardos) channel of erythrocytes plays a crucial role in K+ loss and dehydration of sickle erythrocytes; a potential therapeutic strategy would be to prevent dehydration by specifically blocking this channel. The authors report here on the activity of the clotrimazole (CLT) metabolite, 2-chlorophenyl-bis-phenyl-methanol, which accounts for a portion of the blockade of the erythrocyte Gardos channel when CLT is given orally to normal volunteers. Administration of a single oral dose of 1 g of CLT to four normal healthy volunteers (approximately 15 mg/kg of body weight) resulted in 51% to 92% peak inhibition of the Gardos channel measured in whole blood 2 to 4 hr later. Inhibition remained detectable for 24 to 34 hr. Inhibition of the Gardos channel correlated best with the summed levels of CLT plus its two major metabolites (P < .002; apparent IC50 = 0.65 +/- 0.19 microM). In vitro experiments with 2-chlorophenyl-bis-phenyl-methanol revealed dose-dependent inhibition of K transport and displacement of specifically bound 125I-charybdotoxin. Thus, the imidazole ring of CLT, which is required for antimycotic activity and associated with most of the historically observed toxicity, is not necessary for inhibition of the Gardos channel.

Administration, Oral↗
PubMed1995

Solitary renal melanoma? A case with long survival after initial treatment.

A case of a solitary melanocytic renal tumor with no apparent primary lesion or metastasis is reported. Pathologically the tumor was composed of cells with brown pigmentation that strongly reacted to monoclonal antibody HMB-45 immunohistochemically. Few mitotic figures, mild nuclear atypia and nucleolar prominence were observed. These findings confirmed that the tumor cells were melanogenetic but the malignant potential of the tumor was low in comparison to that of typical malignant melanoma. The patient is doing well 44 months after partial resection of the renal tumor and postoperative chemotherapy. The interesting pathological feature may account for the unique clinical course.

Female↗
PubMed1995

Analysis of the neurofibromatosis 2 gene in human breast and hepatocellular carcinomas.

The neurofibromatosis 2 gene (NF2) mapped to chromosome 22q is a recently isolated tumor suppressor gene that participates in the tumorigenesis of cells of embryonic neural crest origin. The structural similarities between the NF2 product, merlin-schwannomin, and the band 4.1 family raise the possibility that merlin may participate in a wide range of cell activities, in which the cytoskeleton latticework has important roles to play. In order to examine the significance of NF2 in general carcinogenesis, comprehensive analyses of 68 cases of breast carcinoma, which shows frequent loss of heterozygosity at chromosome 22, and 48 hepatocellular carcinomas of different histological grade were performed. No mutation was detected by the polymerase chain reaction-single-strand conformation polymorphism method for six exons of NF2 in any of the cases examined, suggesting that NF2 may be less important in the tumorigenesis of breast and liver cancers than in that of cancers originating from the neural crest.

Base Sequence↗
PubMed1995

HPLC measurement, blood distribution, and pharmacokinetics of oral clotrimazole, potentially useful antisickling agent.

Clotrimazole (CLT) has recently been shown to be a potent and specific inhibitor of the Ca(2+)-activated K+ channel and to thereby prevent K+ loss and cellular dehydration of sickled erythrocytes. This evidence suggests that oral CLT may be a useful new therapy for sickle cell disease. Here, we describe the development of an HPLC assay to measure CLT, a method we used to study the pharmacokinetics and transport of CLT in normal volunteers. The assay's linear range extended to 10 mumol/L; the detection limit was 0.1 mumol/L, analytical recovery 97.7%, and run-to-run imprecision (CV) < 4.7%. In unaffected subjects, CLT concentration peaked within 6 h of oral administration and returned to close to baseline by 24 h. High-density lipoproteins appear to be the main carriers of this drug in both normo- and hypertriglyceridemic plasma. We conclude that the method described here is ideally suited for therapeutic monitoring of CLT concentrations.

Adenosine Triphosphatases↗
PubMed1995

Etiology and prognosis of liver cirrhosis in elderly patients.

We compared the etiology and prognosis of liver cirrhosis in patients age 60 and older with that of patients under age 60 during the 1980s (1981-89, n = 207). Non-A, non-B hepatitis (NANB) was significantly more prevalent in the elderly (p < 0.05), and the mean age of NANB and alcoholic cirrhosis (Alc) were significantly older than those with hepatitis B virus (HBV) (p < 0.05). Evaluation using hepatitis C virus (HCV) antibody also revealed significantly higher mean age of HCV (p < 0.05). Male patient was predominant in the younger patients than in the elderly patients. (M/F = 2.94 and 1.33, respectively) The estimated 5-year survival rate was 73.1% in the younger patients and 60.2% in the elderly patients (p < 0.05). Multivariate analysis revealed that male sex, a lower serum albumin level, and the presence of the encephalopathy were significantly associated with poor prognosis in the elderly, while a lower serum cholinesterase level and a higher indocyanin green retention rate at 15 minutes (ICGR15) were significantly associated with poor prognosis in younger patients. However, causes of deaths were not significantly different between the younger patients and the elderly patients, the proportion of deaths unrelated to liver disease predominated in the elderly patients. Thus, the etiology and the prognostic factors of liver cirrhosis in elderly patients differ from those in younger patients.

Age Factors↗
PubMed1994

Purification and characterization of a rhamnogalacturonase with protopectinase activity from Trametes sanguinea.

In a culture filtrate of Trametes sanguinea IFO 6490, we found a protopectin-solubilizing enzyme, protopectinase-T, that did not degrade polygalacturonic acid. The enzyme was purified to homogeneity with hydrophobic, cation-exchange, anion-exchange, and size-exclusion chromatographies. It had an apparent molecular mass of 55 kDa by SDS/PAGE and 39 kDa by size-exclusion chromatography on Superose 12. The isoelectric point was at pH 8.1. Protopectinase-T was stable from pH 3.0 to 6.0 and at temperatures up to 50 degrees C. The optimum pH for enzyme activity was 4.0 at 37 degrees C, and the optimum temperature was 50 degrees C at pH 5.0. Protopectinase-T catalyzed the release of highly polymerized pectin from lemon peel protopectin.

Chromatography, Gel↗
PubMed1994

Different mutations of the p53 gene in nodule-in-nodule hepatocellular carcinoma as a evidence for multistage progression.

The p53 gene was analysed for mutation in three macro- and micro-scopically different areas of a nodule-in-nodule hepatocellular carcinoma (HCC). Two inner nodules revealed distinct mutations while the surrounding early HCC lesion was negative for mutation. This case clearly demonstrated that the p53 mutation was associated with the progression of HCC from an early to a more advanced stage, and that the primary HCC lesion was composed of genetically heterogeneous subclones. These findings provide direct proof of the involvement of genetic abnormalities in one step of multistage tumor progression.

Carcinoma, Hepatocellular↗
PubMed1994

Generation of hiccup by electrical stimulation in medulla of cats.

The present study has revealed that a hiccup-like response (a brief powerful inspiratory activity accompanied by glottic adduction) can be generated by electrical stimulation to a limited area within the medullary reticular formation of the cat. This finding indicates that there is a neuronal network coordinating the hiccup reflex within the lower brain stem.

Animals↗