Biomedical subjects

S Okada

Publications and source records attributed to S Okada.

At least 631 records · Page 35Linked to original sources

PubMed1995

Chronic active Epstein-Barr virus infection in children in Japan.

The patients with chronic active Epstein-Barr virus infection (CAEBV) in childhood in Japan are described. Among 39 registered cases, 20 patients were males and 19 were females. Unlike the X-linked lymphoproliferative syndrome, there was no hereditary background. The incidence of hypersensitivity to mosquito bites was high (31.3%) as a past history. Most patients exhibited hepatomegaly (92.3%), splenomegaly (87.2%) and fever (84.6%). The incidence of absent anti-EB virus nuclear antigen titres was unexpectedly low (17.1%). Lymphoreticular disorders and cardiovascular diseases were major complications. Twenty-four (61.5%) patients died 6 months to 8 years after the onset, mainly of hepatic failure (eight cases), cardiac failure (five cases), virus-associated haemophagocytic syndrome (three cases) and haematological malignancies (two cases). This study reveals the CAEBV in Japan has several clinical features and should be informative for the pathogenesis of EB virus.

Antibodies, Viral↗

PubMed1995

Single photon emission computed tomography in systemic lupus erythematosus with psychiatric symptoms.

Single photon emission computed tomography (SPECT) with n-isopropyl-p-[123I]iodoamphetamine (IMP) was performed on 20 patients with systemic lupus erythematosus (SLE). Fifteen of the patients showed areas of hypoperfusion. All nine patients who had florid psychiatric manifestations at the time the SPECT was performed had hypoperfusion areas. Four patients who had abnormal SPECT findings during psychiatric remission had psychiatric exacerbation one to six months after the SPECT. Four patients who had no hypoperfusion during psychiatric remission had good psychiatric prognoses. Two patients who had no history of psychiatric abnormality but showed hypoperfusion had psychiatric manifestations one month after the SPECT. The IMP-SPECT may be useful as a biological marker that represents the activity of cerebral involvement underlying psychiatric manifestations and the presence of subclinical CNS involvement.

Adolescent↗

PubMed1995

Grades of exophthalmos and thyrotropin-binding inhibitory immunoglobulin in patients with myasthenia gravis.

Exophthalmos and thyrotropin-inhibitory immunoglobulin (TBII) were examined in myasthenia gravis (MG) patients with normal thyroid function. Exophthalmos was found in 7 of 31 (22.6%) MG patients, and TBII was detected in 4 of 21 (19.0%) MG patients. The grades of exophthalmos did not decrease after extraocular muscle weakness was improved by treatment. Patients with MG whose diplopia was Tensilon unresponsive were only found among those with exophthalmos. TBII was more frequently detected in MG patients with exophthalmos than in those without. The present study revealed that exophthalmos is not rare in MG patients, even if they do not show any signs of Graves' disease other than exophthalmos and their thyroid functions are within the normal limit. The presence of TBII in MG patients may relate to the development of exophthalmos, and exophthalmos itself might enhance ocular symptoms of MG.

Adult↗

PubMed1995

Does homozygosity advance the onset of dentatorubral-pallidoluysian atrophy?

We confirmed a homozygous type of relatively small expansion of CAG triplet repeats (57 repeats) in the short arm of chromosome 12 in a male patient with dentatorubral-pallidoluysian atrophy (DRPLA) by polymerase chain reaction. He showed early onset (age, 17 years) of DRPLA. There was good correlation of the age of onset with the number of triplet repeats. The homozygous state of the expansion of the triplet repeats was responsible for the early onset and severity of his DRPLA.

Adult↗

PubMed1995

Therapeutic efficacy of 5-fluorouracil prodrugs using endogenous serum proteins as drug carriers: a new strategy in drug delivery system.

To establish a novel drug delivery system for 5-fluorouracil (5FU), we have developed a system in which the low-molecular-weight prodrugs of 5FU bound to endogenous serum proteins, thus circulating like those proteins. Subsequently, the prodrugs were slowly hydrolyzed to generate active 5FU in the bloodstream. To examine the therapeutic effect of these prodrugs, we injected them into BALB/c mice previously implanted subcutaneously with Meth A sarcoma. Among the prodrugs, 1-(N-4-chlorophenyl-N-methylcarbamoyl)-5-fluorouracil (5FU-1pCPMC) was effective in reducing tumors and prolonging survival time. The non-hydrolyzable compound, 1-(4-chlorobenzyl)-5-fluorouracil, did not show any therapeutic effect, suggesting that the therapeutic efficacy of 5FU-1pCPMC is due to the sustained release of 5FU from the serum protein-prodrug complex. The data shown here may create a new field in drug delivery system technology.

Animals↗

PubMed1995

DNA-strand breaks induced by dimethylarsinic acid, a metabolite of inorganic arsenics, are strongly enhanced by superoxide anion radicals.

We previously reported that dimethylarsinic acid (DMAA), a major metabolite of inorganic arsenics, induced DNA single-strand breaks (ssb) both in vivo and in cultured alveolar type II (L-132) cells in vitro, possibly via the production of dimethylarsenic peroxyl radicals. Here, the interaction of superoxide anion radicals (O2-) in the induction of ssb in L-132 cells was investigated using paraquat, an O2(-)-producing agent. A significant enhancement of ssb formation was observed in the DMAA-exposed cells when coexposed to paraquat. This enhancement occurred even when post-exposed to DMAA after washing, suggesting that the DMAA exposure caused some modification of DNA such as DNA-adducts, which was recognized by active oxygens to form ssb. An experiment with UV-irradiation, which was likely to induce ssb at the modified region, supported the possibility of DNA modification by DMAA exposure. An ESR study indicated that O2- produced by paraquat in DMAA-exposed cells was more consumed than in non-exposed cells, assumingly through the reaction with the dimethylarsenic-modified region of DNA. The species of active oxygens were estimated by using diethyldithiocarbamate, aminotriazole, diethylmaleate, hydrogen peroxide (H2O2), gamma-irradiation and ethanol. O2- but neither H2O2 nor hydroxyl radicals was very likely to contribute to the ssb-enhancing action of paraquat.

Cacodylic Acid↗

PubMed1995

Pharmaceutical characterization of commercially available intravenous fat emulsions: estimation of average particle size, size distribution and surface potential using photon correlation spectroscopy.

Particle profiles such as the average diameter, size distribution and dispersion, as well as the zeta potential, of commercially available intravenous fat emulsions of high-calorie nutrient fluids (6 products) and drug carriers (4 products) were examined using photon correlation spectroscopy (dynamic light scattering). Wide variations were observed in number-weighted (dn), weight-weighted (dw) and z-average diameters, and dw/dn ratios as a measure of polydispersity. Average size is not sufficient for the pharmaceutical characterization of particles and the determination of size distribution or dw/dn value is essential for more precise information. Although measuring the zeta potential of fat emulsions is of considerable value in estimating their stability on long-term storage, a medium which accurately reflects the environment of the droplets in the system of interest should be chosen when diluting the emulsion.

Absorptiometry, Photon↗

PubMed1995

[Interaction between sodium hyaluronate and tetracyclines].

The interaction between sodium hyaluronate (HA) and 6 kinds of tetracycline (TCs) was investigated by dissolution tests, conductivity, viscosity and turbidity measurements. The 6 TCs were tetracycline (TEC), oxytetracycline (OTC), doxycycline (DOC), methacycline (METC), minocycline (MINC) and chlortetracycline (CTC). In dissolution tests, the release of TCs from the HA solution contained in the cellulose tube was measured and it was found that the 50% release time (T50) of TCs was prolonged with the increase of HA concentration. And the dependence of T50 on HA concentration was different in TCs: the release of METC was most delayed and that of OTC was least affected. By measuring the conductivity of TCs solutions, the binding of TCs to HA was suggested. In viscosity measurements of the HA solution at various pHs, the increase of viscosity was observed by the addition of METC. However in the case of OTC such an increase was not observed. The dissolution tests at various pHs were further tried and the release rate of METC depended on the pH, while that of OTC showed no dependency. Finaly, it was found that T50 of TCs from the HA solution correlates well with the literature values of apparent partition coefficients of TCs between n-octanol and aqueous buffers. Comparing T50 of 6 TCs from carboxymethylchitin (DS = 0.56) solution, it was clarified that the lipophilicity of TCs are more effective to retard the release in the case of the HA solution. From the above results, an electrostatic interaction between HA and TCs can be assumed to be almost similar among 6 TCs.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Interactions↗

PubMed1995

[Activation of retinoic acid (RA)-differentiated HL-60 cells by saponins].

The effect of saponins on the one of major functions of neutrophil, namely the generation of superoxide anion (O2-), was investigated using retinoic acid (RA)-differentiated HL-60 cells (promyelocytic leukemia cells). The generation of O2- from the cells induced by saponins was monitored by the reduction of cytochrome c. All five species of crude saponins studied here, i.e. tea-leaf saponins, tea-seed saponins, ginsenosides, soyasaponins and saikosaponins, stimulated the generation of O2- from RA-differentiated HL-60 cells. Tea-leaf saponins showed the highest stimulating activity, followed by soyasaponins and ginsenosides. The cytotoxic activity of saponins was determined by the dye exclusion method after the incubation of RA-differentiated HL-60 cells with various concentrations of saponins. Saikosaponins and tea-seed saponins exhibited considerable cytotoxic activity and hemolytic activity. To examine the involvement of protein kinase C (PKC) in the neutrophil activation by saponins, the effect of H-7, an antagonist of PKC, on the generation of O2- induced by saponins was investigated. H-7 was found to inhibit the generation of O2- in a dose-dependent manner, suggesting the participation of PKC in the neutrophil stimulating process by saponins. Tea-leaf saponins, ginsenosides and soyasaponins, which had high neutrophil stimulating activity and low cytotoxic activity, seemed to be useful as a biological response modifier (BRM) for the activation of neutrophil.

Cell Differentiation↗

PubMed1995

[Inhibitory effects of hydroquinone-alpha-glucoside on melanin synthesis].

Inhibitory effects of hydroquinone-alpha-glucoside (HQ-alpha-G) on the melanogenesis were investigated and compared with those of arbutin. The levels of inhibitory effects of HQ-alpha-G and arbutin on the tyrosinase activity were nearly the same. Inhibitory effects of both compounds on the melanogenesis, were studied using cultured B16 melanoma cells, and HQ-alpha-G was also found to have a similar effect to that of arbutin without inhibiting cell growth. In this experiment, while HQ-alpha-G hardly inhibited cell growth at 1 mM, arbutin inhibit it significantly at the same concentration. From these results it is suggested that HQ-alpha-G as well as arbutin inhibited the melanogenesis by affecting tyrosinase rather than by killing melanocytes. Furthermore, the melanogenesis of guinea-pigs with brown hair was reduced to about 80% by applying them each compound. The great differences in toxicity to normal human keratinocyte were not recognized between these two glucosides. It is, therefore, considered that HQ-alpha-G is an effective and safe ingredient for cosmetics.

Animals↗

PubMed1995

Further application and evaluation of critical cell number and modifying factors in radiocurability of multicellular spheroids.

Relationship of cure and surviving clonogenic cell number after various doses of X-irradiation was examined in multicellular spheroids of LCT1 human lung adenocarcinoma cells, LCT2 human lung small cell carcinoma cells and FSA1233 mouse fibrosarcoma cells. Some of these spheroids were cured at such doses that considerable number of clonogenic cells still survived after irradiation. Radiocurability was analyzed by comparing total clonogenic cell number in spheroids, cellular radiosensitivity and critical cell number Nc, i.e., the minimum number of clonogenic cells required to produce regrowth. (Nc-1) cells were killed by post-radiation processes and the larger the critical cell number, the more radiocurable. The LCT2 spheroids had the largest critical cell number and were most radiocurable. To investigate underlying mechanisms, modifying effect of heavily irradiated (HIR) tumor cells on the clonogenicity, i.e., plating efficiency of unirradiated tumor cells was investigated. Plating efficiencies with HIR cells showed significant decrease in LCT2 cells, no change in LCT1 cells and increase in FSA1233 cells. The results indicated that in case of LCT2 spheroids some of viable cells surrounded by dying or dead cells might have been killed with unknown toxic effect additional to direct irradiation effect. Thus, critical cell number analysis may be useful to quantify and to compare modifying effect of cellular/environmental factors in curing process of spheroids or tumors.

Adenocarcinoma↗

PubMed1995

Inhibitory effect of phosphorylated oligosaccharides prepared from potato starch on the formation of calcium phosphate.

The inhibitory effect of phosphorylated oligosaccharides, which were prepared from potato starch, on the formation of calcium phosphate in vitro were investigated. Phosphorylated oligosaccharides from potato were fractionated by ion-exchange chromatography into two fractions, PO-1 and PO-2. Fraction PO-1 was composed of maltotriose, maltotetraose, and maltopentaose to which one phosphate group was attached. Fraction PO-2 was predominantly composed of maltopentaose and maltohexaose to which at least two phosphate groups were attached. The average degree of polymerization of dephosphorylated PO-1 and PO-2 was evaluated to be 4.02 and 5.82, respectively. Fraction PO-2 was the main component having an inhibitory effect on calcium phosphate formation. In addition, among the phosphorylated monosaccharides, glucose-1,6-diphosphate and fructose-1,6-diphosphate were more effective inhibitors of the formation of calcium phosphate than glucose-6-phosphate and fructose-6-phosphate. These results suggest that the strength of the inhibitory effect might depend on the number of phosphate groups attached to each sugar molecule.

Calcium↗

PubMed1995

Effects of growth hormone antagonists on 3T3-F442A preadipocyte differentiation.

We have previously shown that a bovine (b) GH antagonist, bGH-M8, which possesses three amino acid substitutions in its third alpha-helix, inhibits mouse 3T3-F442A preadipocyte differentiation. In the current studies, we used the bGH and human (h) GH analogs with single amino acid substitution, bGH-G119R and hGH-G120R, for determining their biological activity using the preadipocyte differentiation assay. Short-term and long-term GH-inducible events were studied during adipose differentiation, including late marker gene expression (adipocyte protein 2), immediate early gene induction (c-fos), and tyrosine phosphorylation of intracellular proteins. The results demonstrated that these GH analogs not only failed to induce these three events, but also antagonized GH induction of c-fos expression and phosphorylation of proteins of apparent molecular mass of 95 kDa. Our present study agrees with the notion that GH must bind to the GH receptor via site one and with a second GH receptor molecule (or with some yet unidentified 'second target') through GH binding site two. This interaction is important for subsequent GH-dependent biological events.

Adipocytes↗

PubMed1995

Blood microvascular organization of the nasal-associated lymphoid tissue of the guinea pig: a scanning electron microscopic study of corrosion casts.

It has previously been confirmed that the guinea pig has aggregations of 10-20 lymphoid follicles at the junction of the nasal cavity and the nasopharyngeal duct. The vascular architecture of this nasal-associated lymphoid tissue (NALT) was studied by the corrosion cast/scanning electron microscope method. The NALT was supplied by branches of the inferior nasal artery. These afferent arterial branches gave off arterioles to the follicles and the interfollicular regions, where the arterioles ramified into capillaries. Some of these arterioles reached the subepithelial region to form a single-layer dense capillary network. The subepithelial capillaries gathered into short collecting venules, which in turn drained into high endothelial venules (HEV) in the interfollicular region. The HEV, which also receives tributaries from the follicular and interfollicular capillary plexuses, descended in the interfollicular regions and finally flowed into the efferent veins at the bottom of the NALT. Indentations impressed by high endothelial cells (HEC) were prominent on the surface of the HEV casts, and their frequency was larger in the upper course or segments than in the lower. This suggests that the incidence of HEC in the upper segments is higher than in the lower segments, and these findings are consistent with the hypothesis that some substances which are taken up into the subepithelial capillaries and transported to the venules induce differentiation and maintain of HEVs.

Animals↗

PubMed1995

Serum bleomycin-detectable iron in patients with thalassemia major with normal range of serum iron.

"Free" iron, a potentially radical-generating low mass iron, and not found in normal human blood, was increased in the serum of blood-transfused thalassemia major patients seen in the Yangon General Hospital, Yangon, Myanmar (Burma). The low mass iron was detected by the bleomycin assay. Fifty-one blood samples were analyzed (from 28 males and 23 females). High "free" iron was detected in 47 sera samples from thalassemia patients. Serum ferritin, which reflects the body store iron, was higher than the normal range (10-200 ng/ml) in 49 patients. On the other hand, serum iron of 39 sera samples fell within the normal range (50-150 micrograms/dl). Four were less than 50 micrograms/dl and eight were more than 150 micrograms/dl. Almost all the patients' sera of normal or higher serum iron level contained "free" iron. Thus, almost all the sera from thalassemic patients from Myanmar contain bleomycin-detectable iron, even when serum iron is within the normal range. In developing countries where undernutrition is prevalent (serum albumin in these patients was 3.6 +/- 0.4 g/dl, P < 0.0001 vs. control value of 4.0 - 4.8 g/dl), normal serum iron does not preclude the presence of free iron in the serum.

Adolescent↗

PubMed1995

Type II citrullinemia associated with neutropenia.

A 37-year-old Japanese man was admitted with delirium and hyperammonemia. He was diagnosed as having type II citrullinemia because of an elevated citrulline level on amino acid analysis and very low hepatic argininosuccinate synthetase activity. He also showed a low neutrophil count and a low serum level of granulocyte colony-stimulating factor. Reduced production of this cytokine and/or impairment of its feedback regulation by the neutrophil count may have played a role in the neutropenia of this patient.

Adult↗

PubMed1995

[A morphological study of interactions of Candida albicans and Streptococcus mutans].

Denture stomatitis is caused mainly by infection of Candida albicans and Streptococcus mutans, the most predominant members of the bacterial flora on denture surfaces. The purpose of this study was to investigate the adhesion in vitro of C. albicans and of S. mutans to acrylic surfaces and their interactions. Concentrations of C. albicans and of S. mutans (mutational phase I and III in which activities of glucosyltransferases are higher and lower respectively) were of high levels (> or = 5.0 x 107 colony-forming-units per ml; CFU/ml). The colonies in brain-heart-infusion (BHI) broth added 5% sucrose incubated at 37 degrees C for 18 and 72 hours. Then the samples were dried and evaporated, and examined by S-700 and S-4100 SEM (HITACHI). It was found that S. mutans (mutational phase I) synthesized water-insoluble glucans concomitantly with the adhesion of both S. mutans and C. albicans to the acrylic surfaces. Also, adhesion of C. albicans, mediated by cell-to-cell interactions with S. mutans (especially mutational phase III), to the surfaces was observed.

Acrylic Resins↗

PubMed1995

White matter changes caused by chronic solvent abuse.

PURPOSE: To examine the brain damage of solvent abusers in Japan, where pure industrial toluene is frequently abused. METHODS: Twenty solvent abusers 17 to 33 years of age with 7.2 +/- 4.0 years of abuse were examined with a 1.5-T MR imaging system. RESULTS: White matter hyperintensities in cerebrum, brain stem, and cerebellum on T2-weighted images were found in seven cases. The extent of white matter change was most clearly shown on proton density-weighted images. The patients with restricted white matter change and intermediate white matter change showed white matter hyperintensities in the brain stem and cerebellum on T2-weighted images, in some cases, with additional hypointensities in the corresponding T1-weighted images. These patients had mainly abused pure toluene. The patients with diffuse white matter change showed obvious brain atrophy, including hippocampal atrophy and thinning of the corpus callosum. These patients had mainly abused lacquer thinner. CONCLUSION: There are some patients with restricted but severe enough change to cause the neurologic symptoms in specific regions, such as the brain stem and/or cerebellum, before the brain atrophy becomes apparent. This suggests that the restricted white matter change represents not only an early change of diffuse white matter change, but at least in some cases also represents a qualitatively different change than that of diffuse white matter change. We suggest that pure toluene has a possible relation to this qualitative difference.

Adolescent↗