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Biomedical subjects

M Sakaguchi

Publications and source records attributed to M Sakaguchi.

At least 451 records · Page 25Linked to original sources

[Separation of HT and HTO in the atmosphere with porous Vycor glass tube].

The continuous selective monitoring of tritium gas (HT) in the air containing HT and tritiated water vapor (HTO) was investigated by using the separation cell made of porous Vycor glass tube. On admitting the air containing HT or HTO into the separation cell, HT permeated immediately through the Vycor tube depending on the partial pressure, however, HTO permeated very slowly through the Vycor tube after initial induction period. The initial induction period was elongated with a rise of the temperature of separation cell and then the permeability of HTO decreased remarkably. In the air containing HT and water vapor, the permeation of HT through the Vycor tube was considerably restricted by the water vapor adsorbed on the Vycor tube at lower temperature (at 25 degrees C) but it was hardly affected by water vapor at higher temperature (greater than 50 degrees C) since water vapor was difficult to adsorb on the Vycor tube. These results indicated that HT in the air containing HT and water vapor can be continuously monitored by using the separation cell made of the porous Vycor glass tube.

Air Pollutants↗

Mechanism of hepatic megamitochondria formation by ammonia derivatives. Correlation between structure of chemicals and their ability to induce the formation of megamitochondria.

Correlation between the chemical structure and the ability to induce hepatic megamitochondria formation was studied by feeding mice and rats diets containing a wide spectrum of ammonia derivatives. Ammonia derivatives with electron-releasing groups, such as hydrazine, phenylhydrazine, hydroxylamine and aniline were effective in inducing megamitochondria. Ammonia derivatives with electron-withdrawing groups, such as formamide, sulfamic acid, acetamide were ineffective in inducing megamitochondria. Inducibility of ammonia derivatives with electron-releasing groups plus electron-withdrawing groups for the megamitochondria formation was dependent upon nucleophilicity of the chemical: 2,4-dinitrophenylhydrazine induced megamitochondria, while acetanilide did not induce megamitochondria. The megamitochondria formation induced by ammonia derivatives was a reversible process. Freeze-fracture studies on megamitochondria indicated that megamitochondria were formed by the fusion of adjacent mitochondria. Phosphorylating capacity of megamitochondria (hydrazine-induced megamitochondria, for example) were normal despite morphological changes. These data might suggest that the nucleophilicity of chemicals plays a key role in the induction of hepatic megamitochondria. These data might also suggest that the phenomenon is an adaptive process to changes of intracellular milieu.

Ammonia↗

Citrullinemia presenting as uncontrollable epilepsy.

We report the case of a 16-year-old girl with a variant form of citrullinemia who had been treated with anticonvulsants for uncontrolled epilepsy during the last 4 years. The diagnosis of citrullinemia was made because she had elevated values for serum citrulline (about 10 times control levels), elevated blood ammonia (over 400 micrograms/dl) and reduced activity of argininosuccinate synthetase in the biopsied liver tissue. Her EEG showed high voltage slow activity, but not triphasic waves, when she had high concentrations of blood ammonia. Treatment with a low-protein diet and sodium benzoate resulted in a normalized blood ammonia level, but her plasma citrulline levels remained unchanged. After the therapy she had neither convulsions nor seizure discharges on EEG, even when all anticonvulsant drug therapy was stopped. Thus it is suggested that hyperammonemia may account for the observed abnormal EEG findings, and triphasic waves on EEG are not always recorded in cases of hyperammonemia.

Adolescent↗

Signal recognition particle is required for co-translational insertion of cytochrome P-450 into microsomal membranes.

Insertion of newly synthesized P-450(1), the major phenobarbital-inducible form of rabbit liver microsomal cytochrome P-450, into microsomal membranes was studied in a wheat germ cell-free translation system programed with total RNA from the liver of a phenobarbital-treated rabbit. P-450(1) synthesized in vitro had the same molecular weight as the mature molecule and was co-translationally inserted into dog pancreas rough microsomal membranes. In the presence of salt-washed microsomes, instead of unwashed ones, the insertion was greatly diminished. It could, however, be restored by supplementation of the system with purified signal recognition particle (SRP), a known component of the membrane translocation machinery for secretory proteins. In the absence of microsomes, SRP inhibited the translation of mRNA encoding P-450(1) and this translation arrest was released by the addition of salt-washed microsomes. On the other hand, SRP did not affect the translation of mRNAs encoding yeast porin and reticulocyte globin, which are mitochondrial and cytosolic proteins, respectively. We conclude that co-translational insertion of P-450(1) into microsomal membranes requires SRP and postulate that P-450(1) possesses an uncleavable signal sequence that can be recognized by SRP.

Cytochrome P-450 Enzyme System↗

Growth of measles and subacute sclerosing panencephalitis viruses in human neural cell lines.

Growth of cell-free subacute sclerosing panencephalitis (SSPE) virus was compared with that of measles virus in three human neural cell lines; neuroblastoma, oligodendroglioma, and glioblastoma. The Edmonston strain of measles virus replicated in these neural cells as efficiently as in Vero cells. In contrast, the growth of the Mantooth strain of SSPE virus was suppressed moderately in neuroblastoma cells and markedly in oligodendroglioma and glioblastoma cells in spite of the induction of apparent cytopathic effects in these cells. Virus adsorption, defective interfering particles, interferon, and temperature sensitivity were not responsible for this low yield of SSPE virus in neural cell lines. Synthesis of viral proteins of SSPE virus was slower than that of measles virus in oligodendroglioma and glioblastoma cells. These results suggest that the slow rate of synthesis of viral proteins may be relevant to the low yield of SSPE virus in neural cells.

Cell Line↗

Induction of megamitochondria in the rat liver by N-propyl alcohol and N-butyl alcohol.

Propyl alcohol and butyl alcohol had similar effects to ethyl alcohol on ultrastructure of liver mitochondria. Rats were given 32% ethyl alcohol, 32% n-propyl alcohol, and 6.9% n-butyl alcohol in drinking water for up to three months. After one month, mitochondria in hepatocytes obtained from the experimental animals became elongated, constricted or cup-shaped with scanty cristae. After two months, mitochondria in some hepatocytes became gigantic. In extreme cases, the megamitochondria exceeded 10 micron in diameter. Coupling efficiencies of hepatic mitochondria obtained from alcohol-fed animals were well preserved despite their drastic morphologic changes.

1-Butanol↗

Effect of dietary unsaturated and saturated fats on azoxymethane-induced colon carcinogenesis in rats.

The effects of dietary unsaturated and saturated fats on chemically induced colon carcinogenesis were examined in male Donryu rats. The rats were fed two types of semipurified diets consisting of 5% linoleic acid or 4.7% stearic acid plus 0.3% essential fatty acid as dietary fats. The rats were treated with azoxymethane (7.4 mg/kg body weight) s.c. once a week for 11 weeks and sacrificed 15 weeks after the last injection of the carcinogen. The rats fed unsaturated fat diet demonstrated a significantly higher incidence of colon tumors [100%], more tumors per rat [2.68 +/- 1.60 (S.D.)], and greater malignant differentiation histologically than did those fed saturated fat diet [76%, 1.79 +/- 1.59, respectively]. Lipid analysis of colon tumors and colon mucosa showed that unsaturated fat diet altered the phosphatide fatty acyl composition of colon mucosa markedly and increased the content of arachidonic acid in the neutral lipid of colon tumors. The altered lipid composition of the mucosa may increase the sensitivity of the colon to the carcinogen, and the excess of arachidonic acid or its metabolites may be the primary agents of cocarcinogenesis of colon tumors. These findings suggest that dietary unsaturated fats have potent cocarcinogenic effects on colon carcinogenesis.

Animals↗

Induction of megamitochondria in the mouse and rat livers by hydrazine.

The correlation between structures of chemicals and their inducibility for megamitochondrial formation was investigated. Since the chemical structure universal to the inducers of megamitochondria previously reported (cuprizone and isonicotinic acid derivatives) is the carbazoyl group (-CONHNH2), semicarbazide (NH2NHCONH2) was tested first. Then, hydrazine (NH2NH2) was tested, replacing the carbazoyl group of semicarbazide by an amino group (-NH2). The present study demonstrates that (1) megamitochondria were induced in mouse and rat hepatocytes by feeding the animals with a diet containing semicarbazide or hydrazine, suggesting that the carbazoyl group was not essential for megamitochondrial formation; (2) hydrazine-induced megamitochondrial formation was a reversible process. Coupling efficiencies and activities of ATPase and cytochrome oxidase of megamitochondria induced by hydrazine were slightly decreased, while the activity of monoamine oxidase was moderately decreased. Freeze-fracture electron microscopy revealed particle-free regions in the outer membranes of megamitochondria fixed with glutaraldehyde at 22 degrees C; the regions disappeared at 25 degrees C, indicating that the temperature of the liquid crystalline to gel state lipid phase transition in the megamitochondrial outer membrane was elevated. It is speculated that chemical structure of inducer of megamitochondria could be simplified to NH2-G (G, substituting group).

Aging↗

Effects of dietary trimethylamine on free amino acid and nonprotein nitrogen levels in muscle of the guppy, Poecilia reticulata, in relation to seawater adaptation.

Guppies Poecilia reticulata acclimated to 100% seawater (SW) had lower taurine and alanine levels in muscle than fish kept in freshwater (FW). The glycine level, in contrast, was higher in SW fish than in FW fish. Levels of other free amino acids (FAA) were comparatively low and little different between fish adapted in FW and in SW. In both FW and SW fish almost all of muscle FAA showed little difference in levels between fish kept on diets containing three different levels of trimethylamine (TMA) (0, 223, and 334 mumol TMA/kg dry weight of diet). Total FAA and nonprotein nitrogen levels in muscle were unaffected by the difference in either the diet species or the ambient salinities. Muscle trimethylamine oxide levels were higher in SW fish than in FW fish. In both salinities, muscle trimethylamine oxide levels in fish on the diets containing 223 and 334 mumol TMA/kg were slightly greater than the level in fish on the TMA-free diet.

Adaptation, Physiological↗

Potential radiosensitizing agents. 6. 2-Nitroimidazole nucleosides: arabinofuranosyl and hexopyranosyl analogues.

New 2-nitroimidazole nucleosides have been synthesized as radiosensitizers of hypoxic mammalian cells in an attempt to reduce the neurotoxicity and to increase the therapeutic efficacy of this class of agents. The trimethylsilyl derivative of 2-nitroimidazole was condensed with 1-bromo-2,3,5-tri-O-benzoylarabinofuranose in the presence of mercuric cyanide to yield anomeric isomers of arabinofuranosides, which were separated by preparative thin-layer chromatography. Reaction of 2-deoxy-1,3,4,6-tetra-O-acetyl-D-glucose or 3,4,6-tri-O-acetyl-D-glucal with 2-nitroimidazole in the presence of an acid catalyst produced alpha and beta isomers of 2',3'-dideoxy-D-erythro-hex-2'-enopyranosides and an isomeric 3-substituted 1,2,3-trideoxy-D-erythro-hex-1-enopyranose. Hydrolysis of the esters was accomplished with sodium methoxide in methanol at 0 degrees C. The radiosensitizing efficacy of these agents was determined against Chinese hamster (V-79) cells in vitro. The 1-(2',3'-dideoxy-alpha-D-erythro-hex-2'-enopyranosyl)-2-nitroimidazole was the most active agent of this series and was found to be superior to misonidazole as a radiosensitizer.

Animals↗

Characterization of canine distemper viruses adapted to neural cells and their neurovirulence in mice.

Interaction of the Onderstepoort strain of canine distemper virus (CDV) with three established human neural cells, i.e. IMR-32 neuroblastoma, 118-MGC glioma and KG-1 oligodendroglioma, was examined, and adaptation of CDV to these cells was also attempted. The unadapted virus was found to grow at relatively low titers in the three neural cells inducing moderate to minimal cytopathic effects (CPE). The virus was successfully grown at high titers in these cells after 8 to 10 passages. Biological characteristics such as growth rate, morphology of CPE and plaque size changed after adaptation. Analysis by SDS-polyacrylamide gel electrophoresis, however, failed to show any difference in the molecular weight of component proteins among the unadapted and three adapted viruses. Inbred DDD strain of mice developed clinical signs after intracerebral inoculation with the unadapted virus but most of them survived with histological lesions of encephalitis. Neuroblastoma-adapted virus induced only transient clinical signs in some animals with mild encephalitic lesions in the gray matter. Increases in neurovirulence were found for viruses adapted to glioma and oligodendroglioma cells. Almost all mice inoculated with these two viruses at 3 weeks of age died within 8 days with histological lesions consisting of hyperemia, edema, severe degeneration of nerve cells and a few giant cells. Demyelinating lesions in the absence of inflammatory changes were observed in the cerebellum, pons and medulla oblongata of animals inoculated with oligodendroglioma-adapted virus.

Animals↗

[Role of the spleen in tumor immunity--with special reference to anti-tumor immunity induced by solubilized and purified tumor-associated antigen].

The effects of post-operative immunization with purified tumor-associated antigen on the development of lung metastases following resection of the Lewis lung carcinoma (3LL) were studied. The soluble tumor-associated antigens were isolated from 3LL cells by detergent solubilization and purified by affinity chromatography on peanut agglutinin (PNA)-agarose. The immunization with subcutaneous injections of PNA-binding glycoproteins at early phase following resection of primary footpad tumors of 3LL resulted in a significant decrease in incidence and size of lung metastases. The delayed immunization, however, failed to suppress the development and growth of metastatic lung tumors after surgery. The suppression of postoperative development of lung metastases was found to depend on timing of immunization following local tumor resection. Splenectomy performed simultaneously with amputation of tumor-bearing leg was completely abolished the decrease in the development and growth of postoperative lung metastases in immunized-mice. Evidence of lymphoid system involvement in the control of metastatic tumor growth was also supported by the observation of in vivo tumor neutralization assay utilizing the spleen cells.

Animals↗

Protective effect of saikosaponin-d isolated from Bupleurum falcatum L. on CCl4-induced liver injury in the rat.

The effects of saikosaponin-d extracted from the roots of Bupleurum falcatum L. on carbon tetrachloride-induced hepatic injury were studied in rats. Pretreatment with saikosaponin-d produced a remarkable inhibitory action on acute hepatic injury by CCl4. A significant inhibition of lipid peroxidation induced by an acute dose of CCl4 in the liver of rats pre-treated with saikosaponin-d was also noted. Continuous injection of CCl4 caused liver cirrhosis in rats but the severity of cirrhosis was reduced in rats treated simultaneously with CCl4 and saikosaponin-d.

Animals↗

Nelaton catheter in non-gravidas for a safe and gradual cervical softening and dilatation: a possible involvement of prostaglandins.

A short Nelaton catheter (No. 7 or 8; diameter: 4.5 or 5 mm) was inserted for 24 hours in the uterine cervix in 89 non-gravidas, including 67 nulliparas. Patients were distributed in four groups depending on the purpose of cervical dilatation: I.U.D. insertion (n = 16), diagnostic curettage (n = 37), hysteroscopy (n = 12), and insertion of radiation applicator in uterine cancer (n = 24). Comparative studies with a smaller number of patients (n = 18) were also performed with a laminaria tent prior to study of the Nelaton catheter. In both the Nelaton and laminaria groups, significant cervical softening and dilatation of the cervix was attained in all cases. After treatment, a Hegar dilator No. 6 to 10 (diameter: 6.5 to 8.8 mm) could be inserted easily without resistance and without the necessity for anesthesia in either group. In the Nelaton catheter group, the tigher the catheter in the cervical canal upon insertion, the higher was the efficiency. The overall efficiency of the Nelaton catheter did not differ significantly from that of laminaria. The Nelaton catheter had several advantages over that of laminaria. No serious side-effects were encountered during the use of the Nelaton catheter compared with laminaria. This simple device proved to be useful as a convenient clinical instrument, particularly in the field of fertility control and for diagnostic and therapeutic purposes of intra-uterine abnormalities. The possible involvement of prostaglandins in the mechanism of action of the catheters is discussed.

Catheterization↗