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Biomedical subjects

Y Takeuchi

Publications and source records attributed to Y Takeuchi.

At least 163 records · Page 9Linked to original sources

Lichen planus with involvement of all twenty nails and the oral mucous membrane.

A 57-year-old man had had deformities of all ten fingernails for one and a half years before presentation and deformities of all ten toenails for the previous six months. The surfaces of the nails were rough, with excessive longitudinal striations. The bases of the nails were slightly hypertrophic, and the tips were atrophic and itchy. A longitudinal nail biopsy including the nail matrix revealed the typical histology of lichen planus. Reticulated pigmentation, maceration, and erosion on the buccal mucous membrane were also discovered. Histological analysis of the buccal mucous membrane revealed lichen planus intermingled with eosinophils. Immunological blood analysis revealed elevated CD4+ T cells and CD4/CD8 ratio. He worked as a tinsmith and had dental metal. The metal series patch test revealed positive reactions to chromate and tin. Treatment with systemic steroids was quite effective in treating the nail lesions.

Atrophy↗

In vitro antitumor activity, intracellular accumulation, and DNA adduct formation of cis-[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)] platinum (II) suspended in lipiodol.

SM-11355, cis-[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)] platinum (II), is a lipophilic platinum complex under clinical development that targets primary hepatocellular carcinoma using Lipiodol as a carrier. SM-11355 was compared with cisplatin (CDDP) using an in vitro evaluation system capable of examining the release characteristics and the cytotoxicity of drugs suspended in Lipiodol. SM-11355 suspended in Lipiodol (SM-11355/Lipiodol) and CDDP suspended in Lipiodol (CDDP/Lipiodol) showed cytotoxic activity against rat ascites hepatoma AH-109A cells in a dose-dependent manner. Their IC50 values following 7-day exposure were 22.3 and 0.40 microg/ml, respectively. Following the subsequent 7-day exposure, from day 7 to day 14 after preparation of the suspension, SM-11355/Lipiodol showed an almost equivalent activity, but CDDP/Lipiodol did not show any activity at all. SM-11355/Lipiodol showed a sustained release into the culture medium over the course of a 14-day exposure. Following the exposure to CDDP/Lipiodol, the platinum concentration in the medium was at its maximum on the first day and remained constant thereafter. Intracellular platinum uptake and formation of platinum-DNA adducts were dependent on the release characteristics of each drug suspension. For SM-11355/Lipiodol, the drug release, intracellular drug uptake, and formation of platinum-DNA adducts over the course of the subsequent 7-day exposure were similar to those observed during the first 7 days. DPC, one of the compounds released from SM-11355/Lipiodol, was taken up by cells and showed formation of platinum-DNA adducts. Thus, this study suggests that SM-11355/Lipiodol may release active platinum compound(s) that bind to nuclear DNA and mediate the cytotoxic activity of SM-11355/Lipiodol.

Animals↗

Cytotoxicity of cis-[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)]-platinum (II) suspended in Lipiodol in a newly established cisplatin-resistant rat hepatoma cell line.

The cytotoxic activity of cis-[((1R,2R)-1,2-cyclohexanediamine-N, N')bis(myristato)]platinum (II) (SM-11355) was evaluated in a cisplatin (CDDP)-resistant tumor cell line, and compared with that of CDDP. H4-II-E / CDDP with acquired resistance to CDDP was established by continuous exposure of a rat hepatic tumor line, H4-II-E, to increasing concentrations of CDDP over 12 months. Compared with the parental cell line, this cell line exhibited an 8.8-fold increase in resistance to CDDP and was not cross-resistant to 1,2-diaminocyclohexane platinum (II) dichloride (DPC). There were no differences in sensitivity to six non-platinum antitumor drugs between H4-II-E and H4-II-E / CDDP, which suggests that H4-II-E / CDDP is not multidrug-resistant. Intracellular platinum accumulation and the formation of a platinum-DNA adduct following CDDP exposure were significantly reduced in H4-II-E / CDDP compared to the parental cell line. The acquired CDDP resistance in H4-II-E / CDDP appeared to be predominantly due to reduced CDDP uptake. H4-II-E / CDDP was also resistant to CDDP suspended in Lipiodol (CDDP / Lipiodol), but was not cross-resistant to SM-11355 suspended in Lipiodol (SM-11355 / Lipiodol). Also, there were no differences in intracellular platinum accumulation or the formation of platinum-DNA adducts after SM-11355 / Lipiodol exposure between H4-II-E and H4-II-E / CDDP. These results suggest that acquired CDDP resistance in H4-II-E / CDDP does not influence the cytotoxic activity of SM-11355 / Lipiodol.

Animals↗

[Evaluation of influenza virus type A detection kit].

We evaluated a new Influenza Virus Type A Detection Kit (InfluA-AD "Seiken") and compared it to virus isolation and RT-PCR using throat swab specimens. Our results were as follows: 1) From 13 specimens in which Influenza virus type A was isolated, InfluA-AD "Seiken" detected 12 while RT-PCR detected 9. 2) From 7 specimens in which Influenza virus type B was isolated, InfluA-AD "Seiken" detected 0 while RT-PCR detected 1. 3) From 2 specimens in which Adeno virus was isolated, InfluA-AD "Seiken" detected 0 and RT-PCR detected 0. 4) From 28 specimens in which no virus was isolated, InfluA-AD "Seiken" detected 6 while RT-PCR detected 8. InfluA-AD "Seiken" showed a sensitivity of 92.3% and specificity of 83.8% when compared to virus isolation. We conclude that the new test will be useful for the diagnosis of Influenza virus type A infection particularly in big commercial laboratories.

Evaluation Studies as Topic↗

Infection of nonhuman primate cells by pig endogenous retrovirus.

The ongoing shortage of human donor organs for transplantation has catalyzed new interest in the application of pig organs (xenotransplantation). One of the biggest concerns about the transplantation of porcine grafts into humans is the transmission of pig endogenous retroviruses (PERV) to the recipients or even to other members of the community. Although nonhuman primate models are excellently suited to mimic clinical xenotransplantation settings, their value for risk assessment of PERV transmission at xenotransplantation is questionable since all of the primate cell lines tested so far have been found to be nonpermissive for PERV infection. Here we demonstrate that human, gorilla, and Papio hamadryas primary skin fibroblasts and also baboon B-cell lines are permissive for PERV infection. This suggests that a reevaluation of the suitability of the baboon model for risk assessment in xenotransplantation is critical at this point.

Animals↗

Associations of self estimated workloads with musculoskeletal symptoms among hospital nurses.

OBJECTIVES: To investigate the prevalence of neck, shoulder, and arm pain (NSAP) as well as low back pain (LBP) among hospital nurses, and to examine the association of work tasks and self estimated risk factors with NSAP and LBP. METHODS: A cross sectional study was carried out in a national university hospital in Japan. Full time registered nurses in the wards (n = 314) were selected for analysis. The questionnaire was composed of items on demographic conditions, severity of workloads in actual tasks, self estimated risk factors for fatigue, and musculoskeletal pain in the previous month. Rate ratios (RRs) and 95% confidence intervals (95% CIs) were calculated by the Cox's proportional hazards model to study the association of pain with variables related to work and demographic conditions. RESULTS: The prevalences of low back, shoulder, neck, and arm pain in the previous month were 54.7%, 42.8%, 31.3%, and 18.6%, respectively. The prevalence of musculoskeletal symptoms among hospital nurses was higher than in previous studies. In the Cox's models for LBP and NSAP, there were no significant associations between musculoskeletal pain and the items related to work and demographic conditions. The RRs for LBP tended to be relatively higher for "accepting emergency patients" and some actual tasks. Some items of self estimated risk factors for fatigue tended to have relatively higher RRs for LBP and NSAP. CONCLUSIONS: It was suggested that musculoskeletal pain among hospital nurses may have associations with some actual tasks and items related to work postures, work control, and work organisation. Further studies, however, are necessary, as clear evidence of this potential association was not shown in the study.

Adult↗

The human serotonin receptor gene (HTR2) MspI polymorphism in Japanese schizophrenic and alcoholic patients.

Epidemiological and genetic studies of alcoholism and schizophrenia have been performed, and in this study, the human serotonin receptor (HTR2) polymorphism was examined in 75 alcoholics and 31 schizophrenic patients. We found that there might not be a significant difference between these psychiatric disease patients and controls in the frequency of the C1/C2 HTR2 gene (MspI polymorphism). The results suggest that the human HTR2 MspI polymorphism might not be associated with a risk factor for developing alcohol dependence or susceptibility to schizophrenia. It is possible that there may be a racial difference in the frequency of the C1/C2 gene between Japanese and Caucasians. Further studies are required to determine whether or not the novel serotonin receptor polymorphism reflects the pathogenesis of alcoholism or schizophrenia.

Alcoholism↗

Developmental changes in cerebrospinal fluid concentrations of monoamine-related substances revealed with a Coulochem electrode array system.

The relationship between age and cerebrospinal fluid concentrations of monoamine-related substances, including kynurenine, were investigated using a Coulochem electrode array system, to clarify developmental changes in monoamine-related substances in the human central nervous system. In neurologically normal children, significant inverse correlations with age were observed for the cerebrospinal fluid concentrations of 5-hydroxytryptophan, 5-hydroxyindole-acetic acid, kynurenine, homovanillic acid, 3-methoxy-4-hydroxyphenyl glycol, and 3-O-methyl-dopamine. The concentrations of their precursors, tryptophan and tyrosine, were not related to age. This is the first comprehensive study revealing developmental changes in monoamine-related substances including their precursors and metabolites.

Age Factors↗

Extensive cell death in thymocytes in colon 26-induced cachectic mice.

Extensive atrophy has been reported to occur in the thymus in a cancer-burden state but the mechanisms of this atrophy have not been fully elucidated. We investigated changes in the thymus in tumour-bearing mice inoculated with two subclones of the murine colon 26 adenocarcinoma cell line: clone 5 (non-cachectic) and clone 20 (cachectic). In clone 20 mice, body weights and thymocyte numbers decreased significantly compared with controls. Flow cytometric analysis of the thymocytes demonstrated that the frequency of single positive cells (CD4+ CD8- and CD4- CD8+) was significantly increased and that of double positive cells (CD4+ CD8+) was significantly decreased in clone 20 mice and, to a lesser extent, in clone 5 mice compared with controls. Serum levels of interleukin 6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) were significantly elevated. These results suggested that thymocyte apoptosis was accelerated in the cancer-cachectic state, and increased GM-CSF might be partly responsible for thymic atrophy.

Adenocarcinoma↗

Regulation of insulin secretion by overexpression of Ca2+/calmodulin-dependent protein kinase II in insulinoma MIN6 cells.

Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) may play a key role in Ca2+-induced insulin secretion. We have previously reported that treatment of insulinoma MIN6 cells with secretagogues activated CaM kinase II and increased the phosphorylation of synapsin I, followed by insulin secretion. Here, we identified isoforms of CaM kinase II in MIN6 cells and rat islets. Immunoblot analysis suggested that the major isoforms of CaM kinase II were beta'e and delta2 at the protein level in MIN6 cells. Only the beta'e isoform was detected in rat islets by both RT-PCR and immunoblot analysis. We transiently overexpressed beta'e and delta2 isoforms in MIN6 cells and confirmed that treatment of cells with tolbutamide and glucose activated the isoforms. Immunoblot analysis with an antibody against synapsin I phosphorylated by CaM kinase II demonstrated that treatment with tolbutamide and glucose rapidly increased phosphorylation of synapsin I and that phosphorylation was potentiated by overexpression of the isoforms. The secretagogue-induced insulin secretion was potentiated by overexpression of the isoforms. Our results further support our conclusion that activation of CaM kinase II and the concomitant phosphorylation of synapsin I contribute to insulin secretion from pancreatic beta-cells.

Amino Acid Sequence↗

Antitumor effects of a novel lipophilic platinum complex (SM-11355) against a slowly-growing rat hepatic tumor after intra-hepatic arterial administration.

The antitumor effects of cis[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)] platinum(II) (SM-11355) were evaluated in a rat hepatic tumor model, and were compared with those of cisplatin (CDDP). A novel slowly-growing rat hepatic tumor model was established by the successive transplantation of rat AH109A tumor into the liver. The drugs, which were suspended in Lipiodol, were administered into the proper hepatic artery of tumor-bearing rats. Tumor growth was suppressed in the group that received SM-11355 suspended in Lipiodol (SM-11355/Lipiodol). Mean tumor growth rates in the groups administered 20 microl of Lipiodol containing 0, 0.02, 0.04, 0.1, 0.2, or 0.4 mg of SM-11355 were 244, 86, 110, 81, 51, and 40%, respectively, 1 week after treatment. Those in the groups administered 20 microl of Lipiodol containing 0.1, 0.2, or 0.4 mg of CDDP were 240, 110, and 45%, respectively. In the groups administered 0.2 and 0.4 mg of SM-11355 or 0.4 mg of CDDP, massive necrosis was observed in the tumor tissue 1 week after drug administration, and the tumors disappeared 4 weeks after drug administration. Serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels were measured as markers of liver damage one day after the drug was administered into the hepatic artery of rats. The minimum toxic dose, which raised serum GOT and GPT levels significantly compared with Lipiodol alone, was 0.2 mg for SM-11355/Lipiodol and 0.1 mg for CDDP/Lipiodol, respectively. The results demonstrated that SM-11355/Lipiodol exerted antitumor activity at a dose that showed no hepatic toxicity in the rat model, but CDDP/Lipiodol did not.

Alanine Transaminase↗

In vitro cytotoxicity of cis[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)] platinum(II) suspended in lipiodol in rat hepatoma AH-109A cells and human tumor cell lines.

SM-11355, cis[((1R,2R)-1,2-cyclohexanediamine-N,N ')bis(myristato)] platinum(II), is a lipophilic platinum complex. SM-11355 suspended in Lipiodol (SM-11355/Lipiodol) was shown to have antitumor activity against hepatic tumors after intra-hepatic arterial administration in animal models. In this study, the in vitro growth inhibitory activities of SM-11355 and cisplatin (CDDP) following 7-d drug exposure were examined using rat ascite hepatoma AH-109A cells and various human tumor cell lines. In monolayer or suspension cell cultures, SM-11355 did not inhibit the cell growth, whereas SM-11355/Lipiodol had dose-dependent growth inhibitory activities, as did CDDP suspended in Lipiodol (CDDP/Lipiodol). This was also the case in the colony formation assay in agarose gel. CDDP/Lipiodol released platinum compound into the culture medium rapidly, whereas SM-11355/Lipiodol released it slowly but constantly for 7 d. Furthermore, a significant amount of platinum was detected in the cells treated with CDDP/Lipiodol and SM-11355/Lipiodol. These results suggest that Lipiodol plays an important role in the in vitro cytotoxicity of SM-11355, and certain platinum compounds released from SM-11355/Lipiodol have growth inhibitory effects on these cells.

Animals↗

In vitro release of SM-11355, cis[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)] platinum(II) suspended in lipiodol.

SM-11355, cis[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)] platinum(II) is a lipophilic platinum complex. SM-11355 suspended in Lipiodol (SM-11355/Lipiodol) was previously shown to have antitumor effects against rat hepatic tumors after intra-arterial administration. In the present study, the in vitro release of platinum compounds from SM-11355/Lipiodol was examined. A test tube containing 10 ml of saline and 1 ml of SM-11355/Lipiodol was rotated at 5 rpm in a vertical orientation. The platinum concentration in saline gradually increased for 28 d. From HPLC analysis, cyclohexane-1,2-diamineplatinum(II) dichloride (DPC) and cyclohexane-1,2-diamineplatinum(II) chloroiodide (DPCI) were detected in the saline, and the sum of these two compounds was equivalent to the total platinum amount in the saline determined by atomic absorption spectrophotometry at days 21 and 28. DPC showed significant growth inhibitory activities, with IC50 values of 0.1-0.7 nmol/ml in rat hepatoma AH-109A cells and 5 human tumor cell lines, as effective as cisplatin. These findings suggest that SM-11355/Lipiodol exerts antitumor effects by releasing active platinum compounds, and that DPC is one of the candidates of the active compounds.

Animals↗

Use of electroporation to accelerate the skin permeability enhancing action of oleic acid.

Rat skin permeability after treatment by electroporation (newly developed frog type electrode, 100V, 10 pulses), oleic acid/propylene glycol (PG) and a combination of both were investigated using Fourier transformed infrared attenuated total reflectance (FT-IR/ATR) analysis. Electroporation immediately disordered the stratum corneum lipid structure up to a certain threshold level. This action lasted throughout the experiment. This may be attributed to the formation of long lifetime of metastable lipid structures, which may allow molecules to pass to the inside of the stratum corneum due to the electroporation-induced fluidized lipid membranes. Electroporation also altered the protein structure of the stratum corneum. When electroporation was combined with 0.05 M oleic acid/PG, uptake of oleic acid and PG into the stratum corneum was remarkably accelerated compared to the application of only 0.05 M oleic acid/PG to the skin. This indicates that electroporation enables oleic acid and PG to penetrate the stratum corneum easily by disrupting the structure of the latter. PG transfer into the dermis from the epidermis was accelerated, not because of the direct action of electroporation on the dermis, but because electroporation induced the rapidly disordering action of oleic acid on the stratum corneum. Lipid-soluble indomethacin permeated the skin more rapidly when the skin was treated with electroporation plus oleic acid/PG than with 0.05 M oleic acid/PG in vitro.

Animals↗

Novel enantioselective fluorinating agents, (R)- and (S)-N-fluoro-3-tert-butyl-7-nitro-3,4-dihydro-2H-benzo[e][1,2]thiazine 1,1-dioxides.

Enantioselective fluorinating agents, (R)- and (S)-,N-fluoro-3-tert-butyl-7-nitro-3,4-dihydro-2H-benzo[e][1,2]thiazine 1,1-dioxides (BNBT-F, 2) are readily prepared in 3 steps from racemic 3-tert-butyl-7-nitro-3,4-dihydro-2H-benzo[e][1,2]thiazine 1,1-dioxides (5) via optical resolution and fluorination. These agents make accessible both enantiomers of optically active quaternary alpha-fluoro carbonyl compounds in modest to high enantioselectivities. X-ray crystallographic analysis of chiral 2 reveals a unique structure wherein the nitrogen atom is highly pyramidalized and fluorine occupies an axial position.

Crystallography, X-Ray↗

Alpha-bromo-alpha,alpha-difluoroallyl derivatives as synthetic intermediate: nucleophilic substitution of alpha-bromo-alpha,alpha-difluoroallyl derivatives in the presence of palladium catalysts.

The palladium catalyzed nucleophilic substitution of alpha-bromo-alpha,alpha-difluoroallyl derivatives turned out to be an efficient method for the preparation of several fluorinated organic molecules. Several soft carbon nucleophiles regioselectively reacted with 3-bromo-3,3-difluoropropene (BDFP) to give the 3-substituted 1,1-difluoroalkenes. Phenylzinc chloride and tributylphenyltin afforded 1-fluoro-1,3-diphenylpropene. The radical bromination of 3-substituted 1,1-difluoroalkenes provided 1-substituted BDFPs, and a 1-substituted BDFP reacted with carbon nucleophiles to give 1,3-disubstituted 3,3-difluoroalkenes. For the reaction of nitrogen nucleophiles with BDFP, an amine and the sodium salts of the carbamates reacted with BDFP at the gamma-position. However, the sodium salts of the sulfoneamide predominantly attacked at the alpha-position.

Catalysis↗

The aetiology of non-tumorous enhancement in the hepatic hilum shown on CT hepatic arteriography.

The causes of non-tumorous abnormalities in the hepatic hilum seen on CT hepatic arteriography were investigated. 13 patients with non-tumorous defects of portal perfusion in the hepatic hilum on CT arterial portography underwent both CT hepatic arteriography from the common hepatic artery and CT obtained during proper hepatic arteriography. The findings of non-tumorous portal defects on these two angiographic studies using helical CT were compared. In the 13 patients, 14 non-tumorous defects of portal perfusion in the hepatic hilum on CT arterial portography were detected as enhanced areas in 10 regions (dorsum of segment IV, 7/10; dorsum of the lateral segment, 3/4) on CT hepatic arteriography via the common hepatic artery, but none were enhanced on CT obtained during proper hepatic arteriography. In conclusion, the main cause of non-tumorous enhancement in the hepatic hilum seen on CT hepatic arteriography is non-portal direct inflow via the parabiliary venous system.

Aged↗