Immunohistochemical demonstration of GM2-ganglioside in the central nervous system of a 19-week-old fetus of Tay-Sachs disease.
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Brain↗
Biomedical subjects
S Okada
Publications and source records attributed to S Okada.
Study of pathogenesis in twitcher mouse, an enzymatically authentic model of human Krabbe's disease.
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Aging↗
Diabetes insipidus with spontaneous remission.
Pathogenesis of idiopathic diabetes insipidus is unknown and the clinical course of the disease is permanent. However, we observed one patient who was diagnosed of idiopathic diabetes insipidus spontaneously reverted after approximately 13 months. The cause and pathogenesis of the disease were not evident. However, some reversible abnormalities should have been encountered in the hypothalamic-neurohypophyseal system. It is suggested that some unknown reversible impairments of the supraopticohypophyseal tract can cause diabetes insipidus. This case represents a well-documented description of idiopathic diabetes insipidus with spontaneous remission.
Adult↗
Oxygen reduction and lipid peroxidation by iron chelates with special reference to ferric nitrilotriacetate.
A certain iron chelate, ferric nitrilotriacetate (Fe3+-NTA) is nephrotoxic and also carcinogenic to the kidney in mice and rats, a distinguishing feature not shared by other iron chelates tested so far. Iron-promoted lipid peroxidation is thought to be responsible for the initial events. We examined its ability to initiate lipid peroxidation in vitro in comparison with that of other ferric chelates. Chelation of Fe2+ by nitrilotriacetate (NTA) enhanced the autoxidation of Fe2+. In the presence of Fe2+-NTA, lipid peroxidation occurred as measured by the formation of conjugated diene in detergent-dispersed linoleate micelles, and by the formation of thiobarbituric acid-reactive substances in the liposomes of rat liver microsomal lipids. Addition of ascorbic acid to Fe3+-NTA solution promoted dose-dependent consumption of dissolved oxygen, which indicates temporary reduction of iron. On reduction, Fe3+-NTA initiated lipid peroxidation both in the linoleate micelles and in the liposomes. Fe3+-NTA also initiated NADPH-dependent lipid peroxidation in rat liver microsomes. Although other chelators used (deferoxamine, EDTA, diethylenetriaminepentaacetic acid, ADP) enhanced autoxidation, reduction by ascorbic acid, or in vitro lipid peroxidation of linoleate micelles or liposomal lipids, NTA was the sole chelator that enhanced all the reactions.
Adenosine Diphosphate↗
Endogenous virus genomes become hypomethylated tissue--specifically during aging process of C57BL mice.
In an attempt to find out a cause for age-dependent derepression of endogenous viruses, extents of DNA methylation at the endogenous B- and C-type ecotropic viruses in brain, liver and spleen of C57BL/6NJc1 were examined at three ages, newborn, young adult and old. Both endogenous viruses showed a slight but significant tissue-specific either hypo- or hypermethylation during post-natal developmental phase in the three tissues. After maturation, however, no such change was detectable at most of the sites examined. The exceptions were C-type ecotropic virus in brain and B-type virus in spleen, where the age-dependent decreases of methylation were observed. The changes seemed to be continuations of preceding developmental hypomethylation. They indicated that the hypomethylation could be one of the causes for the age-dependent derepression of endogenous virus. It was further suggested that a mechanism to stop the developmental changes of DNA methylation at the maturation of individuals would be important in considering the reasons for the changes in senescent phase.
Aging↗
Mechanical properties of hydroxyapatite-reinforced gelatin as a model system of bone.
The elastic Young's modulus of hydroxyapatite-reinforced gelatin as a mechanical model system of bone was measured as a function of the volume fraction of hydroxyapatite, phi h. Initially, the Young's modulus gradually increased with an increase in phi h and then increased rapidly in the vicinity of phi h approximately 0.2. The phi h dependence of the Young's modulus was analysed by means of the theory of composite materials. It was found that with the increase in phi h the initial uniform stress deformation mode of the sample changed to the uniform strain deformation mode. The non-linear character in phi h dependence of the Young's modulus of this system was considered to reproduce well the novel behaviour of the mechanical properties of bone as a function of the mineral fraction. The situation was considered to be similar to a percolation problem. A preliminary analysis revealed that the critical exponent about the viscosity of the system accorded with the theoretically expected value. The result may present the evidence that the discontinuous point in mechanical properties of bone would be originated from an interaction such as a percolation of mineral particles on a matrix protein.
Biomechanical Phenomena↗
Chemical form of tumor-tropic 99mTc-DL-homocysteine.
Analyses of the chemical forms of 99mTc-complexes provide important information for the development of a new tumor-tropic 99mTc-labeled radiopharmaceutical. We attempted to determine the chemical form of 99mTc-DL-homocysteine (99mTc-Hcy) which was previously reported to be tumor-tropic. By analyzing the functional residues of Hcy in the 99mTc-Hcy molecule, it was estimated that the sulfhydryl and amino residues participated in the chelate formation. Gel filtration analysis of 99mTc-Hcy indicated that its molecular size was bigger than that of 99mTc-penicillamine monomer. The analysis also indicated that 99mTc-Hcy complex seemed to be a relatively small oligomer. Although an uncertainty remains on the valency of Tc in 99mTc-Hcy molecule and the accurate molecular size of this complex, its putative chemical form is described.
Adsorption↗
Intensification of tumor affinity of 99mTc-DL-homocysteine by cooperative use of SH-containing compounds.
The enhancement of tumor-specific distribution was investigated on 99mTc-DL-homocysteine (99mTc-Hcy), a possible tumor-imaging agent. In vitro HPLC analysis showed that 99mTc-Hcy did not bind to nonmercaptalbumin but to mercaptalbumin in blood. When glutathione, homocysteine or cysteine, which converts albumin from the mercapto- to nonmercapto-form, was intravenously injected into 99mTc-Hcy predosed mice bearing Ehrlich solid tumor, the SH-containing compounds did not affect the radioactivity distribution in tumor, but decreased that in blood to less than half that of untreated animals. In vitro gel filtration analysis showed that glutathione released 99mTc-Hcy from albumin. Free 99mTc-Hcy produced in blood by the treatment was rapidly excreted into urine. These results suggest that the combination of 99mTc-Hcy and SH-containing compounds is useful for tumor-imaging.
Animals↗
Age-associated changes in DNA methylation and mRNA level of the c-myc gene in spleen and liver of mice.
Age-associated changes in DNA structure and mRNA level were studied for the c-myc gene in spleen and liver of mice at 2, 14 and 26 months of age. Neither amplification nor rearrangement of the gene was detected in either tissue at any age. However, a significant alteration was observed in the methylation profile. The profile of the gene and its vicinity was determined using various methylation-sensitive restriction enzymes. In both tissues, the gene had an unmethylated domain ranging from -2 kb upstream of the 5' end of the first exon to the 3' end of the first intron. It was flanked by partially methylated regions, where age-dependent changes as well as tissue specificity were observed. In the spleen, age-related hypomethylation was observed at both the 3' and 5' sides of the domain. In contrast, hypermethylation was found in the liver only at the 3' side. The steady-state level of c-myc mRNA showed a drastic decrease in liver from youth to middle age, while splenic mRNA changed little. The correlation between the changes of mRNA and DNA methylation is discussed.
Aging↗
Induction of mesothelioma by intraperitoneal injections of ferric saccharate in male Wistar rats.
Iron appears to play a major role in catalysing free radical production, leading to lipid peroxidation and DNA damage. We, therefore, investigated the effect of colloidal iron deposited in the peritoneum. Wistar male rats were given either ferric saccharate, ferric saccharate and nitrilotriacetic acid (NTA), NTA or saline. NTA was shown previously to 'free' iron to promote lipid peroxidation and an iron chelate of NTA is known to be carcinogenic to the kidney. Iron at a dose of 5 mg kg-1 day-1, and saline at a dose of 0.5 ml day-1 were injected i.p. for 3 months. NTA at a dose of 83.5 mg kg-1 day-1 was give i.p. for 5 months. All the rats were killed about a year later for histological examination. In nine of the 19 rats treated with ferric saccharate, mesothelial tumors were induced in the serosa of the tunica vaginalis or the length of the spermatic cord. Among rats treated with ferric saccharate and NTA, seven had localised mesotheliomas in the above locations and six had wide-spread peritoneal mesotheliomas. No mesothelial tumors developed in either NTA treated or saline treated rats. No pleural mesotheliomas were found in any group. These findings add to the evidence that iron is involved in some carcinogenic processes.
Animals↗
Effect of tritiated water on female germ cells: mouse oocyte killing and RBE.
The relative biological effectiveness (RBE) of tritiated water (HTO) was investigated using mouse immature oocytes. Juvenile mice, having immature oocytes that are highly sensitive to radiation killing, were exposed to HTO, 137Cs gamma rays, 60Co gamma rays, or 252Cf fission neutrons. The 137Cs gamma rays were used to simulate the changing dose rate (but not the radiation quality) received from HTO (see section 2). On the 14th day after birth, female ICR strain mice were injected once in the abdominal cavity with HTO at levels of 1.70, 3.40, 6.81, or 10.21 MBq/10g body weight, and their ovaries were removed 2 weeks after the injection. (The cumulative doses are equivalent to 0.039, 0.077, 0.159 and 0.246 Gy, respectively.) The survival rate of oocytes was determined by light microscopy inspection of serial sections, and the results of the different exposures were compared. The number of surviving oocytes decreased exponentially with increasing dose of HTO or 137Cs, and RBEs of HTO compared to 137Cs gamma rays ranged from 1.1 to 3.5. The relative effectiveness of the different types of radiations was compared, and the results of the comparison, in order of increasing effectiveness, was 137Cs, 60Co, HTO, and 252Cf. The RBE of 252Cf compared to 60Co gamma rays ranged from 1.6 to 3.5.
Animals↗
Induction of chromosome aberrations in human lymphocytes by monochromatic X-rays of quantum energy between 4.8 and 14.6 keV.
The induction of chromosome aberrations was studied in human peripheral blood lymphocytes irradiated in vitro with synchrotron-produced monochromatic soft X-rays of quantum energy in a range between 4.8 and 14.6 keV. These X-rays were more effective in producing chromosome aberrations (dicentrics and rings) than 60Co gamma-rays. The efficiency increased with increasing LET of the photoelectrons and their associated Auger electrons, reaching a maximum at a track average LET (L delta = 100, T) of around 4 keV/microns, and tended to decrease or become rather refractory with further increase of LET. This unique LET dependency was consistent with the dual nature of chromosome aberration formation, and interpreted as a reflection of a limited range of photoelectrons as compared with the size and intranuclear geometry of the elemental chromatin fibres as vehicles of damage interaction.
Chromosome Aberrations↗
Prevalence of small round structured virus infections in acute gastroenteritis outbreaks in Tokyo.
During the three-year period from 1984 to 1987, 506 acute gastroenteritis outbreaks involving 14,383 patients were reported to the Bureau of Public Health, Tokyo Metropolitan Government. Eighty (4,324 patients) of 150 outbreaks (4,860 patients) from which etiologic agents were not identified were subjected to virological investigation. Spherical particles of 28-32 nm in diameter with capsomere-like structures on the surface were detected in patients' stool specimens. Buoyant density of the particles appeared to be 1.36 to 1.40 g/ml in CsCl. Seroconversion to the particles was observed in patients by immune electron microscopy. From these observations, we concluded that the detected particles were members of small round structured virus (SRSV), and that they were implicated in the etiologically ill-defined outbreaks encountered. Prevalence of SRSV infections in these outbreaks was examined by electron microscopy. SRSV was positive in 83.8% of the outbreaks, and 96.4% of the cases. SRSV-positive outbreaks usually occurred during winter in contrast to bacterial outbreaks which often occurred in the summer season. Of 80 outbreaks examined, 53 were associated with the ingestion of oysters, and the remaining 27 mostly with food other than oysters. Oyster-associated outbreaks usually occurred on a small scale, while unassociated ones on diverse scales ranged from family clusters to large outbreaks.
Acute Disease↗
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. Report of an autopsy.
We present an autopsy report on a 14-year-old girl with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), placing emphasis on the mitochondrial enzymatic histochemistry of the 3 types skeletal muscle and cardiomyocytes. Generalized muscular atrophy, cardiac hypertrophy, cerebral cortical laminar necrosis, basal ganglia calcification and liver steatosis were observed. In the skeletal muscles, modified Gomori's trichrome staining demonstrated scattered ragged red fibers, and histochemical staining for mitochondrial enzymes showed intense positivity in the subsarcolemmal zones of some muscle fibers. Some of the hypertrophic cardiomyocytes also showed a ragged red appearance with the modified Gomori's trichrome stain. Histochemical staining for mitochondrial enzymes showed patchy loss of enzymatic activity in the myocardium. Electron microscopically, extreme accumulation of enlarged mitochondria and severe loss of myofibrils was observed in both skeletal muscle fibers and cardiomyocytes. The arteriolar smooth muscle cells also showed a mild increase in mitochondria.
Acidosis, Lactic↗
Western blot (immunoblot) assay of small, round-structured virus associated with an acute gastroenteritis outbreak in Tokyo.
Small, round-structured virus (SRSV) was detected in a stool specimen of a patient during an acute gastroenteritis outbreak in Tokyo and was tentatively named SRSV-9. SRSV-9 was purified by sucrose velocity gradient centrifugation after CsCl density gradient centrifugation. The buoyant density of SRSV-9 appeared to be 1.36 g/ml in CsCl. A Western blot (immunoblot) assay using the biotin-avidin system revealed that SRSV-9 was antigenically related to the Hawaii agent but distinct from the Norwalk agent and contained a single major structural protein with a molecular size of 63.0 +/- 0.6 kilodaltons. The prevalence of SRSV-9 infection in Tokyo was surveyed by the Western blot antibody assay by using a crude virus preparation as the antigen. Seroconversion was observed in 56.5% of the patients involved in the outbreaks from which SRSV was detected by electron microscopy.
Acute Disease↗
Promotion of nasal absorption of insulin by glycyrrhetinic acid derivatives. I.
Nasal absorption of insulin in rats was enhanced by addition of sodium glycyrrhetinate (GA Na), dipotassium glycyrrhizinate (GZ K2), and carbenoxolone (glycyrrhetinic acid hydrogen succinate) disodium salt (GAHS Na2). The latter agent was the most effective. On addition of 1% GAHS Na2, plasma immunoreactive insulin levels in rats showed a maximum level of 0.75 mU/ml at 15 min and plasma glucose levels were decreased to about 25 mg/dl after nasal administration of 10 U/kg insulin. In a comparison of the absorption rates of insulin by nasal and intravenous (i.v.) routes in rats, nasal absorptions of 10 U/kg insulin in the presence of 1% GAHS Na2, 0.5% GA Na and 1% GZ K2 were 26.5%, 13.2% and 14.5% of that in the case of a 5 U/kg i.v. dose, respectively. Hemolytic activies of GAHS Na2, GA Na and GZ K2 were milder than those of Na caprate and Na laurate, and nasal leucine aminopeptidase activity was more strongly inhibited by GAHS Na2 than by medium chain fatty acid salts, sodium glycocholate, GA Na or GZ K2. Therefore, it is suggested that GAHS Na2 is a very useful promoter which dose not irritate the nasal mucosal membrane or degrade insulin.
Absorption↗
Liposomes prepared from synthetic amphiphiles. I. Their technetium labeling and stability.
In order to apply liposomes prepared from synthetic amphiphiles containing amino acid residues to radiopharmaceuticals, their labeling with 99Tc or 99mTc and stability in saline or in serum were investigated. These liposomes were highly labeled by embedding stearylamine-diethylenetriamine pentaacetic acid as a ligand of technetium. The labeling was more efficient at pH 7.0 than at pH 4.0 or 8.5. Among these technetium-labeled liposomes tested, liposomes containing the alanine residue were stable in saline or in 50% serum at 37 degrees C for at least 24 h, in contrast to liposomes (phosphatidylcholine: cholesterol = 1:1 molar ratio) whose stability had been enhanced by adding cholesterol.
Chemical Phenomena↗
Mutagenicity of dimethylated metabolites of inorganic arsenics.
The genotoxic effects of dimethylarsinic acid (DMAA), one of the main metabolites of inorganic arsenics in mammals, and its further metabolites were investigated using Escherichia coli B tester strains. When H/r30R (wild-type; Exc+Rec+) and Hs30R (uvrA-; Exc-Rec+) cells were incubated with DMAA for 3 h in liquid NB medium, many more revertants appeared in sealed tubes than in the control, but this was not the case in unsealed tubes, suggesting that volatile metabolites of DMAA caused the mutagenesis. By gas chromatography-mass spectrometry (GC-MS), dimethylarsine and trimethylarsine, known to be volatile metabolites in microorganisms, were detected in the gas phase of DMAA-added tester strain cell suspensions in sealed tubes. Among these arsines, dimethylarsine was mutagenic in WP2 (wild-type; Exc+Rec+) and WP2uvrA (uvrA-; Exc-Rec+), while trimethylarsine was not. The mutagenesis induced by dimethylarsine required oxygen gas in the assay system; the number of revertants markedly increased in an oxygen-replaced system and diminished in a nitrogen-replaced one. These results suggest that the reaction product(s) between dimethylarsine and molecular oxygen is responsible for the mutagenesis. The significance of this mutagenesis in the genetoxic action of inorganic arsenics is discussed.
Arsenic↗