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Biomedical subjects

M Sakamoto

Publications and source records attributed to M Sakamoto.

At least 19 recordsLinked to original sources
PubMed1992

Possible mechanism for zinc protection against cadmium cytotoxicity in cultured vascular endothelial cells.

We investigated the effect of zinc on cadmium cytotoxicity in vascular endothelial cells in a culture system. The cytotoxicity was evaluated by [3H]adenine release assay. Cadmium at 2 microM concentration and above significantly increased the [3H]adenine release, but zinc at 80 microM and below did not induce such a response after a 24-h incubation. Metallothionein was induced by cadmium at 0.1 microM and above but not by zinc at 300 microM and below; however, zinc at 10 microM and above significantly decreased cadmium-(2 and 5 microM) induced cytotoxicity. Zinc protection against cadmium cytotoxicity was also observed in the presence of 1 microM cycloheximide. Zinc caused significantly less accumulation of cadmium in the cell layer accompanied with a significant accumulation of zinc. The distribution (%) of cadmium in the particulate fraction of the cells was significantly decreased by zinc. In contrast, cadmium in the cytosol fraction was increased in the cells treated with both cadmium and zinc. Gel filtration chromatography of the cytosol showed that cadmium was capable of being bound to high-molecular-weight proteins and metallothionein. The metallothionein-bound cadmium was not increased by zinc; however, the relative distribution of cadmium in the high-molecular-weight fraction in the cytosol was decreased in cadmium plus zinc-treated cells. From these results, it was suggested that the mechanism by which zinc protects endothelial cells from cadmium cytotoxicity was decreased accumulation of cadmium in the particulate fraction and in the high-molecular-weight fraction in the cytosol of the cells. This alteration is postulated to be caused by both zinc-induced decrease in the intracellular cadmium accumulation and the sequestration of cadmium by cadmium-induced metallothionein.

Adenine↗
PubMed1992

p53 gene mutation spectrum in hepatocellular carcinoma.

In order to clarify the significance of mutation of the p53 tumor suppressor gene in the genesis and development of human hepatocellular carcinoma (HCC) in an aflatoxin B1 low-exposure area, the spectrum, i.e., incidence, type, and site, of p53 gene mutations was examined in 169 tissue samples resected mainly from Japanese patients using single-strand conformation polymorphism analysis and direct sequencing. Forty-nine tumors (29%) showed a p53 mutation (39 point mutations and 10 frameshifts). The point mutations comprised 18 transitions, only 4 of which occurred at CpG sites, and 21 transversions. Two evolutionarily conserved domains, IV and V, contained 65% of all mutations and codon 249 was the most frequent mutation site (7/49). The spectrum of p53 mutation did not differ among HCCs in relation to the type of hepatitis virus infection, sex, age, and background liver disease of patients, tumor size, or presence of metastasis, but incidence and site were significantly associated with the degree of differentiation of cancer cells. In poorly differentiated HCC, p53 mutation was frequent (54%) and clustered on domains IV and V, whereas in well or moderately differentiated HCC, the mutation was less frequent (21%) and equally distributed on domains II to V. Restriction fragment length polymorphism analysis revealed loss of heterozygosity on chromosome 17p in 55 (69%) of 80 informative cases and in 34 (95%) of 36 cases with p53 mutation. Therefore, p53 gene mutation is suggested to occur independently of the type of viral infection or status of preexisting liver disease and to occur preferentially in moderately and poorly differentiated HCCs in association with or after loss of another p53 allele as a late event of HCC progression.

Adult↗
PubMed1992

Mutation pattern of the p53 gene as a diagnostic marker for multiple hepatocellular carcinoma.

Hepatocellular carcinoma, sometimes shows multiple tumor nodules, therefore poses a problem of differential diagnosis between cancers of multifocal and those of metastatic origin. Conventionally, pathological criteria have been used for this purpose, but these are largely subjective. In order to facilitate more objective differential diagnosis of multiple hepatocellular carcinoma, we used the pattern of mutation of the p53 gene as a marker for each tumor nodule. We studied 58 nodules from 26 cases of multiple hepatocellular carcinoma using polymerase chain reaction-single strand conformation polymorphism analysis, a simple method for detecting mutations. p53 gene mutations were detected in 65% (17 of 26) of cases. The internodule mutation patterns were heterogeneous in 11 cases and homogeneous in 6, enabling a multifocal origin to be diagnosed in the former and a metastatic origin in the latter at the genetic level. Moreover, the origin of recurrent tumors was determined from the mutation pattern. It is concluded that analysis of p53 mutations seems to be useful for differentiating the origin of multiple cancers, since the information it yields is essentially objective.

Base Sequence↗
PubMed1992

Chlorination of cellulose with N-chlorosuccinimide-triphenylphosphine under homogeneous conditions in lithium chloride-N,N-dimethylacetamide.

Microcrystalline cellulose was chlorinated with N-chlorosuccinimide-triphenylphosphine under homogeneous conditions in LiCl-N,N-dimethylacetamide. At the early stage of the reaction only replacement of the 6-hydroxyl groups with chlorine was observed, and 3-hydroxyl groups were replaced at a lower rate with Walden inversion. The effects of reaction conditions on the extent of chlorination were studied in detail. More than two equivalents of chlorination reagents per glucose residue were necessary to attain a high degree of substitution (ds) by chlorine, and the maximum ds attained was 1.86. Chlorinated disaccharides were found in the hydrolyzates of chlorodeoxycelluloses hydrolyzed under mild conditions, and their structures were studied by mass spectrometry.

Acetamides↗
PubMed1992

Plasmin stimulates the release of dermatan sulfate from vascular smooth muscle cells in culture.

We investigated the effect of plasmin on the release of sulfated glycosaminoglycans (GAG) from cultured vascular smooth muscle cells. Confluent cultures of vascular smooth muscle cells from bovine aorta were labelled with [35S]sulfate and incubated at 37 degrees C for principally 60 min in a serum-free medium in the presence of plasmin. Plasmin at 10 mU/ml (approximately 2.7 micrograms/ml) and above significantly increased the release of [35S]sulfate-labeled GAG (35S-GAG) from the cell layer after a 60 min incubation. A time course study showed that plasmin at 10 mU/ml significantly increased the 35S-GAG release after 20 min and longer. However, plasminogen at 100 mU/ml and below did not cause a significant change of the 35S-GAG release after a 90 min incubation. A characterization of 35S-GAG revealed that plasmin increased both dermatan sulfate and the other 35S-GAG in the medium. Plasmin at 100 mU/ml enhanced the cell detachment significantly but only slightly. From these results, it was suggested that a endogenous thrombin inhibitor heparin cofactor II may be activated in the liquid phase by dermatan sulfate released from plasmin-stimulated vascular smooth muscle cells when the vascular is disrupted and plasma is exposed to extravessel.

Animals↗
PubMed1992

Different pattern of chromosomal allele loss in multiple hepatocellular carcinomas as evidence of their multifocal origin.

One of the most problematic aspects of surgery for hepatocellular carcinoma (HCC) is the frequent development of multiple tumors. Determination of the origin of multiple tumors, i.e., multifocal or metastatic, is important for predicting the clinical course of the disease after surgery. In order to clarify the origin of multiple tumors of HCC genetically, we examined patterns of loss of heterozygosity (LOH) on chromosome 16 for DNA isolated from 43 HCCs resected from 19 patients by analysis of restriction fragment length polymorphism. The cases were classified macro- and microscopically into 3 groups: multifocal origin; metastatic origin; and undetermined. Classification based on morphological features was shown to be well correlated with patterns of LOH in multiple tumors of HCC. Different patterns of LOH on chromosome 16 were detected in 8 of 11 patients with tumors of morphologically multifocal origin, whereas they were detected in none of 5 patients with tumors of morphologically metastatic origin. Among five patients with tumors of morphologically undetermined origin, a difference of LOH pattern among the tumors was detected in two, whereas in the other three, the pattern was identical between the tumors. A different pattern of LOH among HCCs arising in situ showed that they were composed of different clones, strongly suggesting their independent clonal origin and multifocal development. These results show that not only appropriate morphological observation but also examination of the LOH pattern on a particular chromosome is useful in diagnosis of multifocal HCC.

Alleles↗
PubMed1992

Disposition, behavior, and toxicity of methylcyclopentadienyl manganese tricarbonyl in the mouse.

The disposition and toxicity of methylcyclopentadienyl manganese tricarbonyl (MMT), a potential substitute for lead in gasoline, was studied to investigate the different adverse effects in ddY mice after chronic oral administration at 0.5 g/kg in food for 12 months. There was no significant difference in intake between the control mice and the mice exposed to MMT (MMT group), but those given MMT suppressed weight significantly. The manganese content in the organs of the MMT group was 4.4-1.5 times significantly higher than that of the control group. In the MMT group, the manganese content was highest in the kidney, followed by the liver, thyroid gland, sublingual gland, and prostate gland. The blood manganese level in the MMT group was about 8 times higher than that in the control group. The urinary excretion of manganese in the MMT group was 5.4% of the daily oral intake. The organometallic form of the manganese involved is apparently absorbed more readily than inorganic forms. The stronger toxicity of MMT to the tissue than that of inorganic manganese is attributed to the significantly higher blood and tissue levels of manganese in the MMT group.

Animals↗
PubMed1992

A visual field quantification system for the Goldmann Perimeter.

We have developed a visual field quantification system that can accurately quantify the measurement results by the Goldmann Perimeter (GP). This system calculates the plural indexes introduced in published papers. In recent years, several isopter quantification methods have been proposed. In these methods, the isopters are digitized and the data are input into a computer, after which a computer program evaluates the changes in the isopters quantitatively. However, each program is only able to evaluate private indexes. We have developed a system that quantifies data using multiple methods. This system used five methods that have been introduced in published papers. With this system, a physician can analyze GP data with multiple methods and can diagnose diseases accurately. We have already input about 2500 GP recording papers into the computer by this system. We then calculated the plural indexes, and visualized the temporal changes in the perimetry.

Humans↗
PubMed1992

The effect of a multiple literature database search--a numerical evaluation in the domain of Japanese life science.

In literature database searching, we show that it is necessary to use plural databases for a more improved search. We also compare the results of a single database search with that of multiple database search in the domain of Japanese life sciences. We searched the MEDLINE and EMBASE using the same search terms. There were some differences in the results, owing to differences in the journals and recording methods. We herein show some of the differences in the journals contained in both databases. Furthermore, we show the differences in the number of papers derived from the same journal. Next, as an example of a practical search, we selected some universities in Japan, searched both databases regarding papers published from these universities and then merged the results by hand. According to our results, only 63% of all papers were common to both databases.

Biological Science Disciplines↗
PubMed1992

Effect of cadmium on the monolayer maintenance of vascular endothelial cells in culture.

We investigated the effect of cadmium on the maintenance of the monolayer of vascular endothelial cells to clarify a possible involvement of endothelium injury in cadmium-induced vascular disorders. Endothelial cells from bovine aorta were cultured with cadmium chloride (0.5, 1.0, 2.0 or 5.0 microM) for 24 or 72 h. A histological observation revealed that a de-endothelialized space was formed in the monolayer by cadmium treatment; the number of endothelial cells was significantly decreased by the metal. Cadmium significantly decreased the number of growing endothelial cells with a significant decrease in the [3H]thymidine incorporation, suggesting that cadmium inhibited the cell proliferation. On the other hand, cadmium significantly increased the detachment of [3H]thymidine-labeled endothelial cells from the monolayer with a parallel increase in the lactate dehydrogenase activity in the medium. From these results, it was suggested that cadmium impairs the endothelial cell monolayer; the de-endothelialized space was formed by both an increase in the cell detachment by cadmium cytotoxicity and a retardation of the repair of the space which was due to an inhibition of the cell proliferation caused by the metal.

Animals↗
PubMed1992

Inhibitory effect of lead on the release of tissue plasminogen activator from human vascular endothelial cells in culture.

To evaluate the toxicity of lead on the blood fibrinolytic system, vascular endothelial cells from human umbilical vein were cultured in the presence of lead and the content of tissue plasminogen activator antigen (t-PA:Ag) released into the medium was determined by enzyme immunoassay. It was found that lead significantly decreased the t-PA:Ag release from the cells. Although heavy metals including cadmium, mercury, cobalt, manganese, nickel, zinc and copper as well as lead each had an inhibitory effect, lead was the potent inhibitor. Lead significantly disturbed thrombin up-regulation of t-PA:Ag release and significantly amplified endothelin-1 down-regulation of it. Incorporation of [3H]thymidine into the acid-insoluble fraction of the cell layer was significantly increased by lead; however, that of [14C]leucine was unchanged by the metal. In lead-treated cells, a significant accumulation of lead was observed but calcium content was increased slightly. From these results, it was suggested that lead decreased the release of t-PA:Ag from cultured endothelial cells without nonspecific inhibition of protein synthesis; lead may stimulate the calcium-dependent down-regulation of endothelial cell t-PA:Ag release by calcium or by mimicking calcium.

Calcium↗
PubMed1992

Reversibility of the inhibitory effect of rhodamine B on the proliferation of cultured human lip fibroblasts.

To investigate the reversibility of rhodamine B inhibition of cell proliferation, human lip fibroblast KD cells were cultured for 3 days in the presence of 25 or 50 micrograms/ml of the dye and the effect of removal of the dye from the culture medium on cell histology and on incorporation of [3H]thymidine into the acid-insoluble fraction of the cell layer was investigated. Removal of rhodamine B on the last 1 or 2 days resulted in an increase in cell number, and incorporation of [3H]thymidine was also restored after removal of the dye; [3H]thymidine incorporation by the cells treated with the dye for only the 1st day was the same as that by the control cells cultured without the dye. In conclusion, it was shown that the decrease in KD cell proliferation caused by rhodamine B can be reversed by removal of the dye.

Cell Division↗
PubMed1992

Rhodamine B inhibits collagen synthesis by human lip fibroblasts in culture.

To investigate the effect of the cosmetic dye, rhodamine B, on the metabolism of collagen in fibroblasts, confluent KD cells, an established cell line of fibroblasts from human lip, were cultured for 6 h in a serum-free medium in the presence of the dye at 100 micrograms/ml and below. It was found that rhodamine B significantly decreased the content of procollagen type I C-terminal peptide antigen in both the cell layer and the medium with an only slight decrease in the cell number. Rhodamine B significantly decreased the incorporation of [3H]proline into either the collagen-digestible protein or the non-collagen protein in the cell layer. The incorporation of both [3H]thymidine and [14C]leucine into the acid-insoluble fraction of the cell layer was significantly decreased by rhodamine B; the activity of lactate dehydrogenase that leaked into the medium was not changed by the dye. From these results, it was suggested that rhodamine B has the capacity of decreasing the collagen content of the fibroblast cell layer of the human lip, which may result from a non-specific inhibition of protein synthesis without non-specific cell damage. Rhodamine B may impair the formation of extracellular matrix which is important for the maintenance of the lip tissue.

Cell Count↗
PubMed1992

Protective effect of copper against cadmium cytotoxicity on cultured vascular endothelial cells.

We investigated the effect of copper on cadmium-induced cytotoxicity on vascular endothelial cells from bovine aorta in a culture system. Cytotoxicity was evaluated by the [3H]adenine release assay and the histological observation. After a 24-h incubation, cadmium exhibited a significant cytotoxicity on confluent cultures of endothelial cells in a dose-dependent manner, while copper only slightly did after a 24-h incubation. It was found that copper (5 microM) significantly decreased cadmium (1 and 2 microM) cytotoxicity; histologically, formation of de-endothelialized areas in the cell layer caused by cadmium was reduced by copper. The accumulation of cadmium in the cell layer was significantly decreased by copper; however, that of copper was unaffected by cadmium. It was therefore suggested that copper significantly protects cadmium-induced cytotoxicity on cultured endothelial cells primarily through decreasing the cellular cadmium accumulation.

Animals↗
PubMed1992

Effects of manganese forms on biogenic amines in the brain and behavioral alterations in the mouse: long-term oral administration of several manganese compounds.

This work has identified the relative toxicity of four forms of manganese, using biogenic amine levels, tissue retention, weight gain, and activity scores as criteria. Male mice were chronically treated with four forms of manganese administered orally, mixed with the diet, for 12 months. The food intake for the control mice and the mice exposed to manganese was similar, but the manganese treatment reduced normal weight gain in the mice. The Mn levels were higher in some parts of brain after feeding insoluble salts than after the soluble salts. The concentration of manganese was significantly increased in the liver and spleen of the manganese carbonate-exposed group, compared with the concentration in the control group. Manganese dioxide feeding lowered dopamine and increased homovanilic acid. Since manganese dioxide is a powerful oxidizing agent in organic chemistry, it possibly enhanced the oxidative metabolite of dopamine. Accumulation of manganese in the brain correlated with reduced hypothalamic dopamine levels in the manganese acetate-exposed group; and the amount of manganese accumulated correlated with the intensity of suppression of motor activity. These findings indicate that manganese dioxide is more toxic than divalent manganese. Of the divalent manganese compounds, manganese acetate seemed to have the greatest toxic effect.

Animals↗
PubMed1992

Characterization of Trypanosoma cruzi isolates from Paraguay, using restriction enzyme analysis of kinetoplast DNA.

Eleven Paraguayan strains of Trypanosoma cruzi, from Chagas' disease patients and the bug vectors, were examined by restriction endonuclease analysis of kinetoplast DNA using Hae III, Msp I, Eco RI, HinfI, Taq I and Rsa I. Four schizodeme-profile groups were identified. Group 1 had much simpler profiles than groups 2, 3 and 4 and, although there were homogeneous profiles in the latter three groups, each group could be distinguished from the others. The profiles of group 1 could not be matched with any of the standard strains from Brazil, Chile and Columbia included in the schizodeme comparison. The profiles of groups 3 and 4 shared most features with those standards of the Brazilian Z2 zymodeme.

Adolescent↗