Biomedical subjects
Publications and source records attributed to S Matsui.
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Rat liver glutathione S-transferases (RX: glutathione R-transferase, EC 2.5.1.18) were found to adsorb S-carbamidomethyl glutathione linked to Sepharose CL-4B via lysyl or aliphatic diamine spacers of various carbon chain lengths (-NH-(CH2)n-NH-, n = 2, 4, 5, 6, 8 and 10). Proteins were eluted specifically by reduced glutathione. The affinity of the enzymes for the adsorbent increased with increase in the carbon chain length of aliphatic diamine spacers used. Adsorbent having a free carboxyl group within the spacer moiety had high capacity and was specific for glutathione S-transferases. The transferases were specifically eluted from the column in high yield by low concentrations of glutathione. Enzymes purified by the lysyl spacer adsorbent were homogeneous in sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and contained most of the hepatic glutathione S-transferase isozymes in isoelectric focusing. Oxidized glutathione and S-methyl glutathione were equally effective as reduced glutathione in eluting glutathione S-transferases from the adsorbent, but gamma-glutamylcysteinylglycineamide or gamma-glutamylcysteinylglycine-1-methyl ester were not effective. These data suggested that the free carboxyl group of glycyl moiety of glutathione might also be important for the specific binding of the transferases to this adsorbent.
Fusion of fresh lymphocytes from a Bloom syndrome (BS) patient with those of normal subjects or a BS heterozygote resulted in complete normalization of the frequency of sister chromatid exchanges in the chromosomes of BS cells. This normalization took place by the first mitosis in hybrid cells. In contrast, cultivation of BS lymphocytes with those of normal subjects or the BS heterozygote had no effect on sister chromatid exchanges. The cell fusion experiments suggest that the normalization on the sister chromatid exchanges. The cell fusion experiments suggest that the normalization of the sister chromatid exchange frequencies in BS cells can be achieved by factors conserved in the cells of various mammalian species. These findings are compatible with the concept that BS is a recessive genetic mutation at regulatory levels of the DNA repair function.
Mechanical and enzymatic disaggregation procedures have been utilized for the preparation of materials suitable for chromosome examination of tissues from various kinds of solid tumors. A great number of the cells disaggregated with the latter procedure were observed to attach to the bottom of culture flasks after 2 days in vitro; cells obtained with the former method were not attached. In general, the enzymatic procedure yielded a significantly larger number of viable cells that would undergo mitosis after short term culture and considerably improved the quality of banding as compared to the mechanical method. However, there were no significant differences among the basic karyotypes observed in the cells obtained by the mechanical approach versus those seen following the enzymatic method. This evidence, together with the high success rate of karyotyping in the enzyme-treated preparations, suggest that this should be the procedure of preference for cytogenetic examination of various tumors, particularly where in the past karyotypic examination has been very difficult, e.g., the early stages of tumor development.
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Nifedipine, the Ca++ antagonistic coronary vasodilator, was administered by oral, sublingual and enema routes. 1) In 6 severe hypertensive patients (systolic pressure greater than or equal to 200 mmHg, diastolic greater than or equal to 120 mmHg), nifedipine, administered orally, induced prompt and reliable fall of arterial pressure (systolic pressure: -28% of control level, diastolic: -27%). 2) In 10 patients with hypertensive emergencies, including malignant hypertension, intracranial bleeding, hypertensive encephalopathy and acute hypertensive heart failure, sublingual and enema administration of nifedipine were performed with excellent hypotensive efficacy. 3) Pressure began to fall within 5--15 min, 30 min and 30--60 min after sublingual (or dissolved), enema and oral (capsule), respectively, and reached its lowest levels in the next 10--20 min. The fall of pressure lasts for 2--4 hours. 4) In the combination of nifedipine with alpha-methyldopa, antihypertensive response in short-term was increased about +11% over nifedipine alone and lasted for 8 hours. In combination with beta-blocker (propranolol), hypotensive efficacy increased +39% over nifedipine alone, but the effective duration of this combination was the same as nifedipine alone. 5) Side effects, including dryness of the mouth and burning sensation in face and legs, were observed in few patients.
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The preferential association of choriocarcinoma with complete moles has long been recognized. In fact, of all forms of pregnancy that lead to choriocarcinoma, the risk associated with hydatidiform moles is 2000 to 4000 times greater than that of normal pregnancy or abortion. In order to corroborate the cell lineage between hydatidiform moles and choriocarcinoma, we investigated the chromosomal constitution and polymorphisms in the latter cells. Three choriocarcinomas from three women with a previous history of hydatidiform moles were examined chromosomally. Two hundred thirteen cells were analyzed for their chromosome number by conventional Giemsa staining; karyotyping of 33 cells with Q- and C-banding revealed 13 kinds of structural abnormalities unequivocally identified as of clonal origin. Two cases exhibited involvement of the long arm of chromosome 1 in rearrangements. Complete homozygosity and exclusive inheritance of a paternal genome would be expected if the tumor arose from a preceding molar pregnancy. However, the heterozygosity observed in choriocarcinoma cells suggests no common cellular lineage with complete moles; the latter originate through fertilization of an "empty egg" by a haploid sperm, followed by duplication of the chromosomes. Several possibilities have to be considered for the origin of choriocarcinomas, since it seems unlikely that alterations in the paracentric areas of the marker chromosomes occurred during tumor development. One possibility is that moles which are characterized by heterozygosity may transform into choriocarcinomas. Another possibility is that such tumors may originate from trophoblasts of the conceptuses rather than from moles.
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To determine the structural basis of chromatin assembly that leads to chromosome formation in mitosis, crosslinks were introduced by formaldehyde between contiguous components within chromosomes. Crosslinked stable products were then observed by electronmicroscopy after non-crosslinked portions were briefly digested by trypsin to unfold chromosomes.--When the DNA-histone crosslink was the primary product, trypsin readily unfolded the whole chromosome structure while preserving the 250 A unit chromatin fiber intact; only a single unit fiber was tracked within the centromere region connecting the arms of each chromatid. When a histone polymer was formed by a prolonged formaldehyde crosslinking, trypsin digestion gave rise to chromatin fibers interacting with others at certain distances, and the typical chromosome structure remained unchanged. Regardless of the degree of crosslinking, there were neither thick supercoiled unit fibers nor proteinaceous cores.--These results suggest that the fiber connection may represent, to some extent, the interacting sites of folded chromatin fibers in situ within chromosomes, and also that the 250 A unit fibers are the sole, highest structural basis in chromosomes. Since virtually no appreciable histone digestion took place in the crosslinked chromosomes, the observation that even after DNA-histone crosslinking the fiber interacting sites were accessible to trypsin preferentially over other portions, may be consistent with our recent results that the exposed, lysine-rich tails of histones represent such interacting sites.
Comparative metabolic fate of labelled chromium chloride and sodium chromate and interaction of these compounds in the rat liver and blood were investigated after their oral and intravenous administration. Gastrointestinal absorption of both compounds was below 1% of the oral dose, but trivalent chromium showed higher radioactivity than the hexavalent form in rats (biological half-life: CrCl3 91.79 days, Na2CrO4 22.24 days). The higher residual activity of the trivalent chromium was also observed after intravenous administration. Both forms of chromium were excreted more in the urine via the kidney than in the intestinal tract after intravenous administration. When 51CrCl3 and Na251CrO4 were injected into rats, in the time-distribution patterns of 51Cr in the organs, a significant difference was shown between oxidation states of the two compounds, especially in subcellular fractions of the liver and blood constituents. This significant difference mainly observed in the rat blood came from the fact that trivalent chromium possessed a high binding activity for transferrin in plasma, while hexavalent chromium was permeable into red cells and bound with hemoglobin.
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