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Biomedical subjects

S Okada

Publications and source records attributed to S Okada.

At least 1,081 records · Page 60Linked to original sources

[Pyridoxine Hydrochloride Reference Standard (Control 871) of National Institute of Hygienic Sciences].

The raw material of pyridoxine hydrochloride was examined for the preparation of "Pyridoxine Hydrochloride Reference Standard". Analytical data for the sample were as follows: loss on drying is 0.01%; pH 2.94; melting point 205.2 degrees C (decomposition); IR spectrum same as the Pyridoxine Hydrochloride Reference Standard (Control 801); TLC indicates no impurities; nitrogen is 6.77% (Theoretical value 6.81%); and assay 99.5% by non-aqueous titration, 99.8% by UV spectroscopy, and 100.2% by measuring chloride ion. Based on the above results, this raw material was authorized to be Reference Standard of National Institute of Hygienic Sciences.

Chemical Phenomena↗

[Tocopherol Acetate Reference Standard (Control 881) of National Institute of Hygienic Sciences].

Tocopherol acetate was tested for the preparation of "Tocopherol Acetate Reference Standard (Control 881)". Analytical data obtained were as follows: infrared spectrum, same as Tocopherol Acetate Reference Standard (Control 851); absorbance, E1%1cm (284 nm) = 43.7; thin-layer chromatography, contaminants were not detected; high-performance liquid chromatography, one contaminant was detected; assay, 100.0%. On the basis of those results, this material was authorized as the Japanese Pharmacopoeia Standard (Control 881).

Chromatography, High Pressure Liquid↗

[Neutrophil dysfunction in chronic neutrophilic leukemia without rearrangements of bcr and immunoglobulin heavy chain genes].

A 67-year-old man was admitted to our hospital with abdominal distension due to hepatosplenomegaly. The peripheral blood revealed Hb content 6.5 g/dl, platelet count 4.7 x 10(4)/microliter, and WBC count 105.8 x 10(3)/microliter with 88% of mature neutrophils. The neutrophil alkaline phosphatase score was 421. Bone marrow aspiration revealed hypercellularity with increased megakaryocytes and myeloid hyperplasia. 46, XY, del 20(q 11) without Philadelphia chromosome was identified by cytogenetic study. The patient was diagnosed as having chronic neutrophilic leukemia and was successfully treated with busulfan, but he died of atypical mycobacteriosis about 20 months later. Analysis of neutrophil function demonstrated diminution of deformability, random mobility, and chemotaxis, but almost normal phagocytosis and bactericidal capacity. Southern analysis showed no rearrangements of breakpoint cluster region (bcr) gene and immunoglobulin heavy chain gene.

Aged↗

[Analysis of tumor curability in terms of cellular radiosensitivity and its application to physico-chemical therapy modes].

Analysis of curability of multicellular spheroids (a model of solid tumor) in terms of cellular radiosensitivity showed that radiosensitivity of spheroids is determined by four factors; total cell number, two parameters (mean lethal dose and extrapolation number) of cellular radiosensitivity and critical cell number. For example, an increase of cell number and two parameters make spheroids more radioresistant, while an increase of critical cell number makes them more radiosensitive. Various therapy modes could be analyzed by this analysis: Increased radioresistant of larger tumors could be attributed mostly to increased cell number and increased cellular radiosensitivity. Radiosensitization by fast neutrons could be due to increased radiosensitivity of composite cells. Hyperthermia showed a critical cell number below 1, indicating a killing mechanism different from X-rays. One of the future areas to be explored for better therapy mode could be how to increase the critical cell number through modification of environmental conditions (e.g., making the irradiated cells more able to survive or easy to die.)

Cell Count↗

Impaired cholesterol esterification in cultured skin fibroblasts from patients with I-cell disease and pseudo-Hurler polydystrophy.

Cholesterol esterification was examined in cultured skin fibroblasts from patients with I-cell disease and pseudo-Hurler polydystrophy by incubating cells pretreated without fetal calf serum for 48h, with (14C) cholesterol for 24h. Impaired cholesterol esterification was found in these cells and free cholesterol was accumulated in plasma membrane and Golgi fractions. This impairment was also induced in control cells by adding leupeptin (20 micrograms/ml) or monensin (2 micrograms/ml). These findings suggest the importance of the role of lysosomes for esterification of cholesterol and give a hint as to the basic defect in type C Niemann-Pick disease.

Autoradiography↗

Cirrhosis of the liver induced by cupric nitrilotriacetate in Wistar rats. An experimental model of copper toxicosis.

Rats intraperitoneally injected with a daily dose of cupric nitrilotriacetate (Cu-NTA), which contained 4 to 7 mg of copper/kg body weight, showed submassive liver necrosis, hemolytic anemia, and acute renal tubular necrosis at the beginning of the experiment and intermittently after 4 weeks of injections. All rats that survived over 8 weeks exhibited liver fibrosis with portal-portal, portal-central, and central-central bridging. In all rats that survived over 16 weeks, micronodular cirrhosis of the liver or extensive liver fibrosis was observed. The copper content of the cirrhotic/fibrotic liver was above 250 micrograms/g dry weight. Electron-microscopic x-ray analysis at day 93 revealed that copper stored in secondary lysosomes was always accompanied by a proportional amount of sulfur (correlation coefficient, 0.98; P less than 0.005). An experimental model of copper toxicosis in terms of copper-induced cirrhosis of the liver was established with exogenous copper chelated by nitrilotriacetate.

Acetates↗

[A case of reexpansion pulmonary edema during thoracotomy].

A case of reexpansion pulmonary edema during thoracotomy is presented. A high edema fluid-plasma protein concentration ratio suggested an increase in pulmonary vascular permeability. A marked increase in the percentages of polymorphonuclear leukocytes (PMN) and high concentration of PMN-elastase in edema fluid suggested activated PMN-mediated vascular endothelial injury, which caused an increase in permeability. Edema fluid and plasma contained high concentrations of Thromboxane B2 and 6-keto-PGF1 alpha at the stage of increased permeability. This suggested these chemical mediators participated in the mechanisms of increased permeability in reexpansion pulmonary edema.

Adult↗

Sex differences in ferric nitrilotriacetate-induced lipid peroxidation and nephrotoxicity in mice.

Since male A/J mice are much more susceptible to both acute and subacute nephrotoxicity and the carcinogenic effect of ferric nitrilotriacetate than female mice, sex differences in the lipid peroxidation level after ferric nitrilotriacetate use were examined. The effects of orchiectomy and testosterone were also investigated. Male and female A/J mice were given a single intraperitoneal injection of ferric nitrilotriacetate (3 mg of iron/kg of body weight) and then thiobarbituric acid reactivity was determined in the liver and the kidney. Only male mice showed high thiobarbituric acid reactivity after 30 min, with the kidney showing higher activity than the liver. Castrated male mice showed a reduction in thiobarbituric acid reactivity, whereas testosterone-pretreated castrated male or testosterone-pretreated female mice showed increased thiobarbituric acid reactivity. In addition, daily intraperitoneal injections of ferric nitrilotriacetate resulted in the death of all normal male mice within 6 days, whereas all female and castrated male mice survived 3 months of treatment. Thus, male and female mice showed differences in ferric nitrilotriacetate-induced toxicity as reflected in the degree of lipid peroxidation and mortality.

Animals↗

Effect of dietary vitamin E on ferric nitrilotriacetate-induced nephrotoxicity in rats.

The effect of dietary vitamin E on renal tissue damage and lipid peroxidation was investigated following treatment with ferric nitrilotriacetate (Fe-NTA) in rats. Almost 100% renal proximal tubular necrosis was observed in the vitamin E-deficient rats following Fe-NTA treatment (5 mgFe/kg body wt, ip) as early as 12 hr. In the vitamin E-supplemented rats, no injury was observed in the proximal convoluted (cortical) tubules, although some injury was seen in the medullary outer stripe (mostly pars recta of the proximal tubules) 24 hr after Fe-NTA treatment. The tissue lipid peroxidation was dose-dependently increased 1 hr after a single ip injection of Fe-NTA (1 to 10 mg Fe/kg body wt). Vitamin E-deficient animals had an increased tissue content of thiobarbituric acid-reactive substance following Fe-NTA treatment, whereas vitamin E-supplemented animals showed suppressed lipid peroxidation. This study indicates that vitamin E provides some protection against the nephrotoxicity and associated lipid peroxidation induced by Fe-NTA.

Animals↗

Chemical properties of technetium-99m-DL-homocysteine, a possible tumor-imaging agent.

The chemical properties of 99mTc-DL-homocysteine (99mTc-Hcy) showing high accumulation in several experimental tumors were investigated. The form of tumor-tropic 99mTc-Hcy was a polymeric complex which appeared at void volume on Sephadex G-15 by eluting with 5 mM Hcy. This complex changed into smaller complexes of ca. 600 molecular weight in the presence of 150 mM NaCl and 5 mM Hcy, suggesting that 99mTc-Hcy was a complex composed of smaller polymers which are weakly bound together by an ionic bond. The complex showed a negative charge. The Hcy/Tc molar ratio in the complex was approximately 2 and no Sn was detected.

Animals↗

A case of membranous lipodystrophy complicated by Fanconi's syndrome.

A case of membranous lipodystrophy complicated by Fanconi's syndrome is described. A 40-year old man complaining of pain in his legs was admitted to our hospital. Roentgenograms showed cystic changes in the long bones. Biopsy of the affected lesion of the femur revealed a peculiar membranocystic structure in the marrow that is typical of membranous lipodystrophy. He had a neuropsychiatric disorder which is often associated with this disease. Laboratory studies were remarkable for renal proximal tubular dysfunction, i.e., Fanconi's syndrome. Membranous lipodystrophy is a rare, hereditary disease that has been reported mainly from Japan and Finland. This is the first case of this disease complicated by Fanconi's syndrome. The possible relationship between these disorders is discussed.

Adult↗

A case of late variant form of infantile Krabbe disease with a partial deficiency of galactocerebrosidase.

A female was diagnosed as a late variant form of infantile Krabbe disease at 1 year and 3 months because of the late onset of regressive clinical course, decreased motor nerve conduction velocities, high cerebrospinal protein concentration and partial deficiency of galactocerebrosidase (15.6%) in the cultured skin fibroblasts. She showed normal development until 8 months when she lost her ability of sitting alone after febrile infection, and died accidentally at 2 years and 4 months. A considerable residual enzyme activity may correlate to the milder clinical course of this case.

Cells, Cultured↗

Cure, cell killing, growth delay and fragmentation of X-irradiated human melanoma HMV-I multicellular spheroids.

Human melanoma, HMV-I, multicellular spheroids were irradiated and cure was determined by the absence of cellular outgrowth. Their cellular radiosensitivity was measured by the colony-forming ability of cells dispersed from the spheroid. Analysis of radiocurability of spheroids in terms of their cellular radiosensitivity predicted three necessary conditions: a linearity of dose versus the double-minus logarithm of curability; constancy of a critical cell number; and constancy of cellular radiosensitivity. These conditions were found to exist in the observed data for each of three size classes of spheroids. Analysis suggests that cellular radiosensitivity in multicellular spheroids with diameters of 250 and 400 microns was different from that of monolayers, and that the increase of spheroid-control doses was found to be a function of cellular radiosensitivity, total cell number per spheroid and a critical cell number. The critical cell number increased from 0.8 in a 150 microns spheroid to 4 in a 250 microns spheroid and to 57 in 400 microns spheroid. This number is a unique characteristic of multicellular systems and is one important factor in determining their radiocurability. X-ray-induced growth delay of spheroid size was increased with increasing dose. At high doses a sharp increase in delay time was seen, sometimes accompanying fragmentation of spheroids at late postirradiation times. The clonogenic activity of these fragments may serve as a model of exfoliation, the first step of radiation-induced metastasis.

Cell Aggregation↗

Effect of water-soluble iodinated contrast media on pressure-flow relationship of red cell suspension.

The effect of radiological contrast media on blood flow through a vascular network was investigated, taking physical and physiological conditions such as osmolality into account. The perfusion of the bullfrog's hind limbs was performed, with a slight modification of the vertical tube method. The effect of contrast media on red cell deformability was studied by perfusion with erythrocyte suspensions in glutaraldehyde-fixed hind limbs. The echinocytic shape change induced by metrizamide and hypertonic iothalamate solutions caused a marked increase in resistance to flow. When the perfusion with erythrocyte suspension was performed using intact hind limbs, the pressure-flow relationship was influenced by contrast media effects on both red cell deformability and the vascular bed. Ioxaglate had less rheologic effect on the pressure-flow relationship than metrizamide or iothalamate. It could be concluded that contrast media should be isotonic, of low viscosity and chemotoxicity, and that ioxaglate was preferable to metrizamide and iothalamate at equal iodine content.

Animals↗

Oxic and hypoxic cells in a murine squamous cell carcinoma.

[125I]Iododeoxyuridine labeling of a squamous cell carcinoma and follow-up of 125I activity at the tumor in situ revealed that the 125I activity remained at a constant level from the 24th to the 100th hour post-labeling and then decreased with a half time of about 200 hr. Autoradiographic studies with [3H]thymidine showed that the tumor cells were labeled around capillaries, spread through the corded structure (the cord) and finally reached the necrotic regions. One could speculate that the constant 125I period represents the transit time of the labeled cells through the cord and that the decline occurs mostly in the necrotic regions. X-Irradiation shortened the constant period of 125I activity by about 24 hr and accelerated the declining rate in a dose-dependent manner. When tumors were made hypoxic by clamping the legs, the declining rate decreased significantly. When misonidazole (a hypoxic radiosensitizer) was administered before X-rays, the declining rate increased to a level higher than that of the oxic tumors. From the time course studies, it was suggested that the tumor cells immediately after 125I-labeling were oxic, that they became gradually hypoxic during their transit through the cord and that they became anoxic when they reached the necrotic regions.

Animals↗

A family with pseudodeficiency of acid alpha-glucosidase.

A unique family is presented which consists of a patient with the juvenile muscular dystrophy form of glycogenosis type II and four healthy individuals, both parents and sisters, with low acid alpha-glucosidase activity. It was almost impossible to distinguish the homozygote from the heterozygous members by lymphocyte assay alone. In cultured skin fibroblasts, acid alpha-glucosidase activity measured with a synthetic substrate was less than 1% of the normal mean value in the patient and about 15% in the parents. The activity toward glycogen was not detectable in the patient and was about 30% of the normal mean value in the parents. These values are also lower than expected in heterozygotes. To explain these results properly, a new mutant allele of acid alpha-glucosidase is proposed. Both parents could be compound heterozygotes for the pseudodeficiency allele and the juvenile form of glycogenosis type II allele.

Adolescent↗