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Biomedical subjects

A Murakami

Publications and source records attributed to A Murakami.

At least 379 records · Page 21Linked to original sources

Monovalent carboxylic ionophores inhibit transport of carbamoyl-phosphate synthetase I into mitochondria in Reuber hepatoma H-35 cells and cause accumulation of enzyme precursor.

Transport of the precursor for carbamoyl-phosphate synthetase I into mitochondria in Reuber hepatoma H-35 cells was inhibited by adding monensin or nigericin to the culture medium at a concentration of 0.5 microM, and the enzyme precursor accumulated, mainly in the cytosolic fraction. Accumulated precursor was degraded slowly with a half-life of more than 16 min. Valinomycin, nonactin, A23187, X-537A (lasalocid), bromo-lasalocid, and carbonyl cyanide m-chlorophenylhydrazone did not exhibit these effects at concentrations at which they did not inhibit protein synthesis of the cells.

Animals↗

Role of antral mucosa in intestinal phase of gastric secretion in dogs.

This study was performed to investigate the mechanisms and significance of the intestinal phase of gastric secretion. With infusion of 10% liver extract into the duodenum of dogs, serum gastrin levels of the right gastroepiploic vein increased significantly (p less than 0.01). With infusion of the pH 7.0 liver extract, acid and pepsin outputs in non- antrectomized dogs increased significantly (p less than 0.01), as did serum gastrin levels (p less than 0.01). Post-infusion acid output in these dogs was 48 +/- 16% of tetragastrin-stimulated output. With the same infusion, antrectomized dogs showed no significant increase of acid and pepsin outputs and serum gastrin levels. Acid output and serum gastrin levels in non- antrectomized dogs that were infused with pH 2.0 liver extract did not increase significantly. The values of almost all serum amino acids in both types of dogs increased slightly, but insignificantly, with pH 7.0 liver extract. We obtained the following conclusions. The intestinal phase of gastric secretion operates by the mediation of the antral mucosa, from which gastrin is released. Although this phase has some effect, the acid-secretory ability of this phase is masked by inhibitory systems under certain physical conditions.

Animals↗

Platelet cyclo-oxygenase deficiency in a Japanese.

A case of platelet cyclo-oxygenase deficiency in a Japanese was investigated. There was a marked decrease of aggregation with collagen and absence of aggregation with epinephrine and arachidonic acid. The platelet response to a labile aggregation stimulating substance (LASS) was normal. There was no biosynthesis of prostaglandin endoperoxides from arachidonate. The platelets, including granular volume, showed no ultrastructural abnormalities. The responses to various inducers of platelet aggregation, except for arachidonate, were different from the cases described by others. It is concluded that the defective platelet function, due to a deficiency of platelet cyclo-oxygenase, is heterogeneous.

Adult↗

Different concanavalin A binding patterns of malignant and nonmalignant mouse mammary epithelia in monolayer culture.

Concanavalin A (Con A) binding of fixed malignant and nonmalignant C3H/He mouse mammary epithelia in monolayer cultures was examined with markers and labels of various sizes. In Con A-mediated hemadsorption, high epithelial cell densities resulted in the adsorbance of more guinea pig red blood cells per culture dish but fewer per cell. Malignant epithelia adsorbed twice as many red blood cells as did nonmalignant cells at the same cell density. Ferritin-Con A tagged the budding particles of mouse mammary tumor virus and other parts of the epithelial surface evenly. Hemadsorption occurred at the particle-free part of the apical membrane. The amount of 125I-Con A bound per dish, however, was not related to cell density but was almost identical for cells from the same source. Nonmalignant cells bound twice as much 125I-Con A as did malignant cells. The calculated association constants of Con A-binding sites on malignant cells, however, were twice as large as those on nonmalignant cells. This explains, at least partly, the greater number of red blood cells adsorbed by malignant cells. Con A-labeled Sepharose 4B beads were not useful for our purposes, and fluorescein isothiocyanate-Con A did not distinguish between malignant and nonmalignant epithelia.

Animals↗

[Intra-hepato-arterial administration of cis-diammine-dichloroplatinum II (CDDP) for primary or metastatic hepatic cancer].

To study the effectiveness of CDDP for hepatic cancer, intra-hepato-arterial administration of CDDP (0.8-1.0 mg/kg/week) combined with 5-FU (250 mg/body/day) was performed for 10 patients with primary or metastatic hepatic cancer. As the results, partial response was obtained in 6 of 8 evaluable patients. However, the adverse effect was very high rate; leucopenia, thrombocytopenia and vomiting (nausea) were observed in 9, 6 and 6 of 10 patients respectively. The dose limiting factor of CDDP was not a nephrotoxicity but a bone marrow depression in this series. Though a noticeable antitumor effect of this modality was obtained, some improvements should be applied to it to decrease the adverse effect.

Adult↗

Preparation of oligodeoxyribonucleoside methylphosphonates on a polystyrene support.

An efficient procedure is described for synthesizing deoxyribonucleoside methylphosphonates on polystyrene polymer supports which involves condensing 5'-dimethoxytrityldeoxynucleoside 3'-methylphosphonates. The oligomers are removed from the support and the base protecting groups hydrolyzed by treatment with ethylenediamine in ethanol, which avoids hydrolysis of the methylphosphonate linkages. Two types of oligomers were synthesized: those containing only methylphosphonate linkages, d-Np(Np)nN, and those which terminate with a 5' nucleotide residue, dNp (Np)nN. The latter oligomers can be phosphorylated by polynucleotide kinase, and are separated by polyacrylamide gel electrophoresis according to their chain length. Piperdine randomly cleaves the oligomer methylphosphonate linkages and generates a series of shorter oligomers whose number corresponds to the length of the original oligomer. Apurinic sites introduced by acid treatment spontaneously hydrolyze to give oligomers which terminate with free 3' and 5' OH groups. These reactions may be used to characterize the oligomers.

Base Sequence↗

Use of methylphosphonic dichloride for the synthesis of oligonucleoside methylphosphonates.

Methylphosphonic dichloride was used to prepare protected deoxyribonucleoside 3'-methylphosphonate beta-cyanoethyl esters, d-[(MeO)2Tr]NpCNEt, and protected oligonucleoside methylphosphonates in solution. Reaction of d-[(MeO)2Tr]N with methylphosphonic dichloride gives d-[(MeO)2Tr]NpCl. The phosphonylation and subsequent esterification or condensation reactions are each complete within 60 min. The products are readily purified by "flash chromatography" on silica gel columns. d-[(MeO)2Tr]NpCl, or its tetrazole derivative, d-[(MeO)2Tr]Nptet, were tested as intermediates for the synthesis of oligothymidine methylphosphonates on a silica gel polymer support. The average yield per coupling step was 76% and did not increase with addition of more d-[(MeO)2Tr]TpCl. The formation of (5'-5') linked thymidine dimers indicated that the thymidine monomers are clustered closely together on the support. When N is ibuG, the yield for the coupling step on the support is very low. This may be due to steric hindrance of the 3'-phosphonate group by the N-2 isobutryl protecting group.

Indicators and Reagents↗

Induction of carbamoyl-phosphate synthetase I in Reuber hepatoma H-35 by dexamethasone.

Reuber hepatoma H-35 was found to retain the activity of carbamoyl-phosphate synthetase I. The content of this enzyme in H-35 grown in Eagle's minimal essential medium was about half that in rat liver. The enzyme from H-35 was the same as that from rat liver in molecular weight estimated by SDS-polyacrylamide gel electrophoresis, specific enzyme activity, kinetic parameters for ATP and N-acetyl-L-glutamate, and immunological crossreactivity. The enzyme in H-35 was induced by dexamethasone (1.4-fold) but not by glucagon or dibutyryl cAMP. Incorporation of [35S] methionine into the enzyme indicated that the effect of dexamethasone was due to increased synthesis of the enzyme protein (2.1-fold). By labeling with [35S]methionine, the precursor and the mature forms of carbamoyl-phosphate synthetase I were observed in the post-mitochondrial and mitochondrial fractions, respectively. By chasing the labeled cells with unlabeled methionine and cycloheximide, it was observed that the rate of translocation of the precursor into mitochondria is not affected by dexamethasone.

Animals↗

Structural features of very fast sedimenting DNA formed by gene 49 defective T4.

Very fast sedimenting DNA (VFS DNA) of T4 phage, which is formed by infection with a mutant in gene 49, was examined by electron microscopy after mild treatment with DNase I. It showed Y-shaped, branched strands in addition to linear strands. Each branch contained a single-stranded interruption about 60 nucleotides long at its proximal end. The average number of branches per T4 DNA unit was close to the average number of sites susceptible to gene 49 nuclease. Both numbers were consistently changed by the addition of a secondary mutation in a gene involving recombination.

Centrifugation, Density Gradient↗

In vivo study of developmental changes in carbamoyl-phosphate synthetase I in rat liver. Repression of the enzyme synthesis immediately after birth.

The regulatory mechanism of the developmental increase of carbamoyl-phosphate synthetase I in fetal and neonatal rat liver was studied in vivo. The appearance and rapid increase of the enzyme in late fetal period were caused by de novo synthesis of the enzyme protein. The amount of the enzyme protein analyzed by SDS-polyacrylamide gel electrophoresis was proportional to the enzyme activity throughout the period of development. No indication was observed for preexisting protein which could be converted into the active protein. A novel system for the in vivo study of carbamoyl-phosphate synthetase I synthesis was developed. Hepatocytes, mechanically dispersed by repeated passage of the tissue through a pipet, incorporated [35S]methionine into the enzyme. Taking advantage of this system, the regulation of the enzyme synthesis was studied. In vivo synthesis of the enzyme was detected at 4 days before birth and rapidly increased until 1 day before birth. However, the enzyme synthesis was markedly repressed after birth, when the amount of carmamoyl-phosphate synthetase I itself reached the adult level. This result was in a clear contrast with the constant level of the translatable mRNA (Raymond, Y. and Shore, G.C. (1981) Biochim. Biophys. Acta 656, 111-119) and suggested that post-transcriptional regulation is important in addition to the level of mRNA for the regulation of the carbamoyl-phosphate synthetase I level.

Aging↗

Usefulness of antithrombin III and alpha 2-plasmin inhibitor in early differentiation of fulminant hepatitis and severe form of acute hepatitis.

To evaluate the usefulness of antithrombin III (AT III) and alpha 2-plasmin inhibitor (alpha 2PI) in early differential diagnosis of fulminant hepatitis from the severe form of acute hepatitis, the activities of AT III and alpha 2PI were measured in plasma of 15 patients with fulminant hepatitis and 6 patients with severe form of acute hepatitis. The activities of prothrombin time (PT), hepaplastintest (HPT) and thrombotest (TT) were also evaluated. The mean values and the standard errors (SE) for PT, HPT and TT were 21.1 +/- 2.6%, 14.0 +/- 1.6% and 10.3 +/- 1.7%, respectively, in the early stage of fulminant hepatitis and 25.3 +/- 2.4%, 21.6 +/- 4.6% and 15.8 +/- 3.6%, respectively, in the severe form of acute hepatitis. No significant difference in the tests between these two diseases was noted. On the other hand, the mean values +/- SE for AT III and alpha 2PI were 13.7 +/- 4.6% and 25.6 +/- 8.6% in fulminant hepatitis and 70.2 +/- 28.5% and 98.7 +/- 9.7% in the severe form of acute hepatitis. A significant difference between the two diseases was observed. From the above, it is concluded that measuring AT III and alpha 2PI along with PT, HPT and TT is useful for early diagnosis of fulminant hepatitis.

Acute Disease↗

New beta-lactam antibiotics, carpetimycins C and D.

Two new carbapenem antibiotics, carpetimycins C and D have been isolated from the culture broth of Streptomyces sp. KC-6643, which produced carpetimycins A and B. The structures of carpetimycins C and D have been determined to be (5R,6R)-3-[2-acetamidoethyl-(R)-sulfinyl]-6-(1-hydroxy-1-methylethyl) -7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid and (5R,6R)-3-[2-acetamidoethyl-(R)-sulfinyl]-6-(1-hydroxysulfonyloxy-1 -methylethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid, respectively. Studies on the fermentation, isolation and physico-chemical properties of these antibiotics are also described.

Bacteria↗

[New chemotherapeutic method for the treatment of tracheal and bronchial cancers--nebulization chemotherapy].

A new chemotherapeutic method for the treatment of tracheal and bronchial tree cancers, and of lung cancer with invasion to the bronchial tree has been developed. It is named Nebulization Chemotherapy or NC therapy. This method is based on vaporizing the anti-cancer drug (5-Fluorouracil, 5-FU) solution with a supersonic nebulizer, and inhaling the vaporized anticancer drug trans-orally through the bronchial tree. Patients were divided into two groups. The first group, where NC therapy was the main method of treatment used, included 6 patients. Of these, 4 (2CR and 2PR) showed a good anti-cancer response to the treatment. The other was a group receiving combination treatment with our CMAF protocol (cis-platinum, mitomycin C, adriamycin and 5-FU) and NC therapy. This group included 6 patients, 5 of whom (2CR, 2PR and 1MR) showed a remarkable anti-tumor response. Side-effects to the bronchial tree, pulmonary parenchyma or other systemic toxicity have not been noted so far after NC therapy. However, a few patients showed glottitis. Only trace amounts of circulating 5-FU were detected in serial serum samples.

Adenocarcinoma↗

Suppressive B-cell factor (SBF) produced by FcR-bearing B cells; suppression of B, but not non-B-cell proliferation.

B cells that have receptors for the Fc portion of IgG (FcR gamma + B cell) elaborate an immunoregulatory lymphokine termed suppressive B-cell factor (SBF) after binding immune complexes, such as sheep erythrocytes sensitized with IgG anti-sheep erythrocyte antibody (EA). For producing SBF, de novo protein is required, but not DNA or DNA-dependent RNA synthesis. This mediator is released into the culture supernatant of FcR gamma + B cells during 6 to 48 hr after stimulation by EA. SBF suppresses the proliferation of B, but not non-B cells. Thus, it suppressed (i) plaque-forming cell responses in the induction phase in an antigen-non-specific manner, (ii) DNA synthesis of lipopolysaccharide-activated B cells, but neither concanavalin A nor phytohaemagglutinin-activated T cells, and (iii) the proliferation of B but not non-B tumour-cell lines by acting at the G1-S junction in the cell cycle. Concordance of H-2 haplotype between SBF-producing mice and target B cells is necessary for the suppression. Thus, the action of SBF is B-cell specific and antigen-non-specific. Immune complex-mediated negative feedback regulation seems to be operated by lymphokines such as SBF which may be also involved in the surveillance for B-cell tumours.

Animals↗

[Report on 15 cases of multiple primary cancers in our department].

Of 512 gynecological malignant cases treated in our department, 22 were suspected of multiple primary cancer; 15 were confirmed by clinical and pathological findings, representing an incidence of 2.9% (15/512) of all malignant cases. The most frequent sites of other cancers in patients with cervical cancer were intestinal (5/15), mammary (3/15) and urinary (2/15). Nine (60%) of 15 multiple primary cancers were noted within 12 months. Two rare combinations are also reported. There was a patient with Grawitz's tumor (kidney) and epidermoid cancer (uterine cervix) and one with leiomyosarcoma (uterine corpus) and epidermoid cancer (uterine cervix).

Aged↗