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Biomedical subjects

K Uchida

Publications and source records attributed to K Uchida.

At least 217 records · Page 12Linked to original sources

Antiplatelet and anticancer isothiocyanates in Japanese domestic horseradish, wasabi.

6-Methylsulfinylhexyl isothiocyanate (MS-ITC) was isolated from wasabi (Wasabia japonica, Japanese domestic horseradish) as a potential inhibitor of human platelet aggregation in vitro through our extensive screening of vegetables and fruits. In the course of another screening for the induction of glutathione S-transferase (GST) activity in RL34 cells. MS-ITC was inadvertently isolated from wasabi as a potential inducer of GST. MS-ITC administered to rats or mice also showed both activities in vivo. As a result from elucidation of the platelet aggregation inhibition and the GST induction mechanisms of MS-ITC, the isothiocyanate moiety of MS-ITC plays an important role for antiplatelet and anticancer activities because of its highly reactivity with sulfhydryl (-SH) groups in biomolecules (GSH, cysteine residue in a certain protein, etc.).

Antineoplastic Agents, Phytogenic↗

Localization of Smad6 and Smad7 in the rat kidney and their regulated expression in the anti-Thy-1 nephritis.

Under normal conditions, kidney expresses Smad6 and Smad7 most abundantly among the organs of the body. To understand the physiological roles of these Smad expressions in the kidney, we first identified the sites of Smad6 and Smad7 expression in the rat kidney by in situ hybridization. The expression of Smad7 in the rat kidney was only observed in the glomeruli, while Smad6 was expressed in both the glomeruli and thick ascending limb of Henle's loop. In order to investigate whether Smad6 and 7 are also involved in the negative feedback loop of TGF-beta signaling in vivo, we examined the changes of mRNA levels of these Smads in the glomeruli of rat anti-Thy1 (1-22-3) nephritis, a model where the expression of TGF-beta in the glomeruli has been shown to be most up-regulated from day 4 to 14 after the antibody injection. Unexpectedly, 7 days after injection, the levels of Smad6 and Smad7 did not increase but rather decreased to approximately 70% of the levels on day 0. During that period, Smad7 immunostaining was observed in the glomerular endothelial cells (GEN) where Smad3 immunostaining was also observed. This suggested that Smad7 expression was not augmented by the TGF-beta signal in GEN in vivo in anti-Thy-1 nephritis. The absence of up-regulation of these inhibitory Smads may be involved in the pathogenesis of anti-Thy-1 nephritis.

Animals↗

NO(x) contamination in laboratory ware and effect of countermeasures.

Contamination of various types of laboratory wares with NO(x) (NO(-)(2) and NO(-)(3)) was assessed systematically and the effect of extensive washing as a countermeasure was evaluated. Mean NO(x) contamination arising from a model procedure for NO(x) determination in plasma was 0.93 microM (range, 0.35-1.49 microM). The major source of contamination included conical tubes (54.8%) and pipette tips used for transfer of solution (12.3-16.3%). Except for soft glassware, most NO(x) contamination could be washed out by pure water. Although NO(x) contamination in respective laboratory wares could be reduced below detection levels by extensive washing, summation of the contamination through the model procedure could not be completely abolished (but the effect of washing persisted at least 10 days). Heavy contamination was noted in glassware (especially soft glass) and ultrafiltration units, which was difficult to remove. Several types of vacuum blood sampling tubes contained various levels of NO(x). Our results indicated that a small but significant amount of contamination remained in laboratory ware even after extensive washing, and that it is advisable to avoid the use of glassware (soft glass), ultrafiltration units, and vacuum blood sampling tubes during the processing of clinical sampling for the measurement of NO(x).

Blood Specimen Collection↗

Heat-shock preconditioning reduces oxidative protein denaturation and ameliorates liver injury by carbon tetrachloride in rats.

Membrane lipids and cytosolic proteins are major targets of oxidative injury. This study examined the effect of heat-shock preconditioning associated with the induction of heat-shock protein 72 on liver injury, from the aspect of lipid peroxidation and protein denaturation after carbon tetrachloride (CCl4) administration in rats--one of the representative oxidative injuries. Male Wistar rats were divided into two groups, group HS (preconditioned by heat exposure) and group C (not preconditioned). Expression of HSP72 in the liver tissue was confirmed by Western blot analysis. After a 48-h recovery period, all rats were given CCl4 intragastrically. Liver damage was assessed by measuring serum liver-related enzyme levels and adenine nucleotide concentration in the liver tissue. Lipid peroxidation and protein denaturation were evaluated by measuring tiobarbituric acid reactive substances (TBARS) and by immunohistochemical staining of 4-hydroxy-2-nonenal(HNE)-modified proteins in the liver. Survival rates of the rats after CCl4 administration were also compared. Expression of HSP72 was clearly detected in group HS, but not in group C. Heat-shock preconditioning significantly improved the survival rate, suppressed the increase in liver-related enzyme levels and maintained adenosine triphosphate levels (P<0.01 each). HNE-modified proteins--denatured proteins by free radical attack--were significantly less stained in group HS than in group C (P<0.05). However, TBARS levels did not differ between groups. Because heat-shock preconditioning did not alter TBARS levels but reduced HNE-modified proteins in association with the expression of HSP72, it is suggested that HSP72 did not prevent lipid peroxidation but decreased the lipid peroxidation-induced denaturation of proteins. This seemed to be a mechanism of heat-shock preconditioning to ameliorate oxidative liver injury.

Alanine Transaminase↗

Spontaneous remission of a solitary intraspinal synovial cyst of the lumbar spine.

We report on a 15-year-old boy in whom a spontaneous remission of a symptomatic synovial cyst, possibly emanating from the L4-5 facet joint, was noted. The medical history suggested that sport-related overactivity and/or minor trauma was the underlying cause. Conservative treatment for several months may be one treatment option if the cyst wall is not calcified and the symptoms and signs related to radiculopathy show a gradual decrease.

Adolescent↗

Predictability of the progress of secondary osteoarthritis after developmental dislocation of the hip, utilizing inferior edge (of the teardrop)--center (of the femoral head) distance.

We followed-up a group of patients in their youth and then in middle age after they had been treated for developmental dislocation of the hip, and studied whether we could predict the progress of osteoarthritis of the hip when the patients were in the "youth" stage. We studied 21 hips of 21 patients with unilateral dislocation that could be examined twice, in 1975 and 1995, in patients who were treated at our hospital between 1953 and 1963. We measured the acetabular-head index (AHI), center-edge angle (CE angle), and the Sharp angle, and our created index (inferior edge of the teardrop - center of the femoral head distance), and we divided this index by the distance of the inferior edges of the teardrops on both sides. Using these measured values, we studied whether we could predict changes in clinical and radiographic evaluation after a follow-up of 20 years. There was no significant correlation of clinical and radiographic results and AHI, CE angle, and the Sharp angle; however, there was a significant correlation with our created index. The index we created is relatively easily measured and enables us to make a more precise prognosis, in comparison with previously developed indices.

Adolescent↗

Comparison of the therapeutic efficacy of oral doses of fluconazole and itraconazole in a guinea pig model of dermatophytosis.

The therapeutic efficacy of orally administered fluconazole (FLCZ) and itraconazole (ITCZ) in a guinea pig model of dermatophytosis was compared, using the infection intensity of local skin tissue as an index. After Trichophyton mentagrophytes infections had been established in the test animals, the antifungal agents were administered once per day for 14 days. FLCZ had a dose-dependent therapeutic effect and significantly ameliorated infections at doses of 10 and 20 mg/kg per day (both P < 0.01) compared with the untreated control group. The pathogen could not be cultured from previously infected skin tissue from 11% of the animals treated with FLCZ at 10 mg/kg per day, and from 20% of the animals treated with FLCZ at 20 mg/kg per day. The therapeutic efficacy of FLCZ was approximately equal to that of ITCZ administered at the same doses. These results suggest that FLCZ may be a useful treatment for dermatophytosis.

Administration, Oral↗

Composition of cecal bile acids in ex-germfree mice inoculated with human intestinal bacteria.

Germfree (GF) mice were orally inoculated with human fecal suspension or various components of human fecal microbiota. Three weeks after the inoculation, cecal bile acid composition of these mice was examined. More than 80% of total bile acids was deconjugated in the cecal contents of ex-GF mice associated with human fecal dilutions of 10(-2) or 10(-6), or anaerobic growth from a dilution of 10(-6). In these ex-GF mice, deoxycholic acid accounted for about 20% of total bile acids. In the cecal contents of ex-GF mice associated only with clostridia, unconjugated bile acids made up less than 40% of total bile acids, about half of those in other ex-GF groups. However, the percentage of deoxycholic acid in these mice was the same as that in the other groups. These results indicate that dominant anaerobic bacterial combination is efficient for deconjugation of primary bile acids, and that clostridia in the human feces may play an important role in 7alpha-dehydroxylation of unconjugated primary bile acids in the intestine.

Animals↗

Autoimmune-related pancreatitis is associated with autoantibodies and a Th1/Th2-type cellular immune response.

BACKGROUND & AIMS: Although autoimmunity may be involved in some cases of pancreatitis, the mechanism is still unknown. To clarify this, we studied serum autoantibodies, subsets of lymphocytes, and the Th1/Th2 balance of cellular immune responses in patients with autoimmune-related pancreatitis (AIP). METHODS: Seventeen patients with AIP (8 men and 9 women; age, 53.2 +/- 13.0 years) were studied. Autoantibodies including antilactoferrin (ALF) or carbonic anhydrase II antibody (ACA-II) were examined using the enzyme-linked immunosorbent assay (ELISA) or the indirect fluorescein antibody method. Intracellular cytokines (interferon gamma and interleukin 4) and subtypes of peripheral blood lymphocytes were examined by flow cytometry and ELISA. RESULTS: More than one autoantibody was observed in all 17 patients. Serum antinuclear antibody was detected in 13 of 17 patients, ALF antibody in 13, ACA-II antibody in 10, rheumatoid factor in 5, and anti-smooth muscle antibody in 3, but antimitochondrial antibody in none. The serum levels of ACA-II and LF antibody were not correlated. HLA-DR(+)CD8(+) and HLA-DR(+)CD4(+) cells were significantly increased in peripheral blood (P < 0.05). CD4(+) cells producing interferon gamma and the secreted levels were significantly increased compared with those in controls (P < 0.05), but interleukin 4 was not increased. CONCLUSIONS: An autoimmune mechanism against CA-II or LF, and Th1-type immune response, may be involved in AIP.

Adult↗

Mode of action of sesame lignans in protecting low-density lipoprotein against oxidative damage in vitro.

We investigated the antioxidant properties of sesaminol, a major component of sesame oil, on the oxidative modification of human low-density lipoprotein (LDL) in vitro. Sesaminol inhibited the Cu2+-induced lipid peroxidation in LDL in a concentration-dependent manner with an IC50 36.0 +/- 10.0 nM. Sesaminol was a more effective scavenger than either alpha-tocopherol or probucol in reducing the peroxyl radicals derived from 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) in aqueous solution. In addition, as determined by the secondary products of lipid peroxidation identified by using immunochemical methods, sesaminol completely inhibited the formation of 4-hydroxy-nonenal (4-HNE)- and malondialdehyde (MDA)-adducts in a concentration-dependent manner. Probucol and alpha-tocopherol at the same concentration exhibited a lesser inhibitory effect. Our findings suggest that sesaminol is a potentially effective antioxidant that can protect LDL against the oxidation.

Antioxidants↗