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Biomedical subjects

Koichi Kato

Publications and source records attributed to Koichi Kato.

At least 73 records · Page 4Linked to original sources
PubMed2003

Oxidation of the Si(001) surface: lateral growth and formation of P(b0) centers.

More than 100 oxygen-adsorbed configurations with oxygen coverage of up to two monolayers (ML) were studied through first-principles calculations. It was found that oxidation proceeds almost laterally. When the coverage exceeds 1.25 ML, oxygen atoms introduced between the second and third layers are captured at a bridging site in the second layer, generating twofold-coordinated Si atoms. Emission of such twofold-coordinated Si atoms leaves weakly bonded Si pairs in the fourth layer. When such pairs happen to be generated close to each other, they transform into a chain of Si trimers with one P(b0) center at each end.

Journal Article↗
PubMed2003

Active arsenic species produced by GSH-dependent reduction of dimethylarsinic acid cause micronuclei formation in peripheral reticulocytes of mice.

Dimethylarsine and trivalent dimethylated arsenic, metabolites of inorganic arsenics, have received considerable attention in current research because of their biological activities. We attempted to determine the appearance of micronucleated reticulocytes (MNRETs) in mouse peripheral blood following intraperitoneal administration of dimethylarsinous iodide (DMI) and trimethylarsine (TMA), model compounds of trivalent dimethylated arsenic and dimethylarsine, respectively. A significant increase in the number of MNRETs was observed with TMA, but not with DMI. Furthermore, MNRETs only appeared with 10.6 mg/kg of dimethylarsinic acid (DMA) following its co-injection with reduced glutathione (GSH). These results suggest that micronucleus formation may need further metabolic reduction of trivalent dimethylated arsenic, i.e. the production of dimethylarsine, by an excess amount of GSH. Meanwhile, the increase in MNRETs by administration of arsenite at 7.6 mg/kg, an equivalent dose to DMA as As, was remarkably diminished by co-administration with GSH. These results indicate that GSH plays an important role in the genotoxic process of arsenics, particularly by dimethylated arsenic.

Animals↗
PubMed2003

The role of polyol pathway in glucose-induced apoptosis of cultured retinal pericytes.

The pathogenesis of pericyte loss, an initial deficit in the early stage of diabetic retinopathy, remains unclear. Recent studies have suggested that polyol pathway hyperactivity and apoptosis may be involved in pericyte loss. The mechanisms of the glucose-induced apoptosis in retinal pericytes were investigated to evaluate the pathogenesis of diabetic retinopathy. Under the 20 mM glucose condition, intracellular calcium concentrations and caspase-3 activities were significantly increased, and reduced glutathione (GSH) contents were significantly decreased compared with those under the 5.5 mM glucose condition. These abnormalities were all significantly prevented by an aldose reductase inhibitor, SNK-860. Glucose-induced apoptosis was partially but significantly prevented by SNK-860, an inhibitor of calcium-dependent cysteine protease, calpain, or GSH supplementation, and completely normalized by a caspase-3 inhibitor. These observations suggest that glucose-induced apoptosis in retinal pericytes, as one of the pathogenic factors of diabetic retinopathy, would be mediated through an aldose reductase-sensitive pathway including calcium-calpain cascade and increased oxidative stress, and that caspase-3 would be located furthest downstream of these apoptotic signals.

Aldehyde Reductase↗
PubMed2003

Parkin binds the Rpn10 subunit of 26S proteasomes through its ubiquitin-like domain.

Parkin, a product of the causative gene of autosomal-recessive juvenile parkinsonism (AR-JP), is a RING-type E3 ubiquitin ligase and has an amino-terminal ubiquitin-like (Ubl) domain. Although a single mutation that causes an Arg to Pro substitution at position 42 of the Ubl domain (the Arg 42 mutation) has been identified in AR-JP patients, the function of this domain is not clear. In this study, we determined the three-dimensional structure of the Ubl domain of parkin by NMR, in particular by extensive use of backbone (15)N-(1)H residual dipolar-coupling data. Inspection of chemical-shift-perturbation data showed that the parkin Ubl domain binds the Rpn10 subunit of 26S proteasomes via the region of parkin that includes position 42. Our findings suggest that the Arg 42 mutation induces a conformational change in the Rpn10-binding site of Ubl, resulting in impaired proteasomal binding of parkin, which could be the cause of AR-JP.

Amino Acid Sequence↗
PubMed2003

N-Glycan structures of squid rhodopsin.

To determine the glycoforms of squid rhodopsin, N-glycans were released by glycoamidase A digestion, reductively aminated with 2-aminopyridine, and then subjected to 2D HPLC analysis [Takahashi, N., Nakagawa, H., Fujikawa, K., Kawamura, Y. & Tomiya, N. (1995) Anal. Biochem.226, 139-146]. The major glycans of squid rhodopsin were shown to possess the alpha1-3 and alpha1-6 difucosylated innermost GlcNAc residue found in glycoproteins produced by insects and helminths. By combined use of 2D HPLC, electrospray ionization-mass spectrometry and permethylation and gas chromatography-electron ionization mass spectrometry analyses, it was revealed that most (85%) of the N-glycans exhibit the novel structure Manalpha1-6(Manalpha1-3)Manbeta1-4GlcNAcbeta1-4(Galbeta1-4Fucalpha1-6)(Fucalpha1-3)GlcNAc.

Animals↗
PubMed2003

Mechanisms of increased insulin resistance in non-cirrhotic patients with chronic hepatitis C virus infection.

BACKGROUND AND AIM: Evidence showing a higher prevalence of diabetes mellitus (DM) in patients with chronic hepatitis C virus (HCV) infection has been accumulating. However, the reason why chronic HCV infection promotes DM remains unknown. In the present study, the authors focused on non-cirrhotic and non-diabetic patients with chronic HCV infection and evaluated the factors responsible for increases in insulin resistance. METHODS: Fifty-six patients diagnosed with HCV-related chronic liver disease were included. Biochemical information including body mass index (BMI), aspartate aminotransferase (AST), alanine aminotransferase, cholinesterase, triglyceride, total cholesterol, hemoglobin, platelet count, glycosylated hemoglobin, immunoreactive insulin (IRI), and serum levels of tumor necrosis factor (TNF)-alpha and HCV-RNA were determined using venous blood samples obtained from each patient after overnight fasting. Homeostasis model assessment of insulin resistance (HOMA-IR), a simple and convenient measure of insulin resistance, was also calculated. The relationship between the stage of liver fibrosis and HOMA-IR, and the clinical factors responsible for the increase in HOMA-IR in non-diabetic patients was investigated. RESULTS: Homeostasis model assessment of insulin resistance and IRI levels increased parallel with the progression of fibrosis. Among the non-diabetic patients with mild to moderate liver fibrosis, BMI, serum levels of AST and TNF-alpha were related with HOMA-IR (BMI: r = 0.395, P = 0.041; AST: r = 0.465, P = 0.014; TNF-alpha: r = 0.396, P = 0.040). In contrast, HOMA-IR related to TNF-alpha (r = 0.526, P = 0.013) in non-diabetic patients with advanced liver fibrosis. CONCLUSION: Collectively, hepatic fibrosis and inflammation appear to play key roles in the increase in insulin resistance in patients with chronic HCV infection.

Aged↗
PubMed2003

Ethyl icosapentate (omega-3 fatty acid) causes accumulation of lipids in skeletal muscle but suppresses insulin resistance in OLETF rats. Otsuka Long-Evans Tokushima Fatty.

Ethyl icosapentate (EPA) is known to improve insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM); however, its mechanism is unclear. In this study, we attempted to determine the mechanism of EPA's effects on insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Administration of EPA caused a reduction in plasma cholesterol and triglycerides, but increased cholesterol and triglyceride contents in skeletal muscle. EPA did not have an effect on glucose or insulin levels. EPA accelerated the glucose infusion rate (GIR) and improved the endothelium-dependent relaxation of OLETF rat the thoracic aorta caused by addition of acetylcholine. However, the improvement observed in endothelium-dependent relaxation disappeared after addition of N(w)-nitro-L-arginine (L-NA). Furthermore, when L-NA and indomethacine were added to the medium, relaxation of the aorta in EPA-treated rats was weaker than that in control rats. These actions may cause NO induction in the endothelium and an increase in prostaglandin I(2) (PGI(2)) and prostaglandin I(3) (PGI(3)) action, which in turn may result in improvement of insulin resistance.

Adipose Tissue↗
PubMed2003

Immobilized culture of nonadherent cells on an oleyl poly(ethylene glycol) ether-modified surface.

Microarrays of living cells are an emerging tool in systems such as reverse transfection. These studies are limited to adherent cells partly because of the difficulty of cell immobilization. Using a newly developed reagent, the biocompatible anchor for membrane (BAM), we show herein the rapid and strong attachment of living nonadherent cells and adherent cells on BAM-modified surfaces. Normal cellular growth was observed for over 7 days on BAM-modified surfaces. We expect this methodology to greatly expand the scope of current cell microarray technology.

Animals↗
PubMed2002

A study of the alumina-silica gel adsorbent for the removal of silicic acid from geothermal water: increase in adsorption capacity of the adsorbent due to formation of amorphous aluminosilicate by adsorption of silicic acid.

Two kinds of adsorbents (Si adsorbent and Al adsorbent) for the removal of silicic acid from geothermal water to retard the formation of silica scales were prepared using silicic acid contained in geothermal water. The Si adsorbent was prepared by evaporating geothermal water, and the Al adsorbent was prepared by evaporating geothermal water after the addition of aluminum chloride. The specific surface area of the Si adsorbent was small and it's adsorption capacity of silicic acid was low. Although the specific surface area of the Al adsorbent was also small, it was significantly increased by the adsorption of silicic acid and it's adsorption capacity was high. Based on the change in the local structure of aluminum ion by the adsorption of silicic acid, the Al adsorbent was considered to be silica particles covered with crystalline aluminum hydroxide. Moreover, it was concluded that the increase in the specific surface area of the Al adsorbent and the decrease in the zeta potential were due to the formation of an amorphous aluminosilicate with a large surface area and a negative charge (one 4-coordinated Al) by the reaction between aluminum ions and silicic acids.

Adsorption↗
PubMed2002

Rational structure-based design of a novel carboxypeptidase R inhibitor.

A novel carboxypeptidase R (CPR) inhibitor, related to potato carboxypeptidase inhibitor (PCI), was designed using rational structure-based strategies, incorporating two principle facts: CPR has a strong affinity for basic amino acids, and the two lysine and arginine residues of PCI are orientated in the same direction and held in close spatial proximity by three disulfide bonds. Initially, a disulfide-bonded fragment of PCI was synthesized showing weak competitive inhibitory activity against CPR. Subsequently, a smaller linear 9-mer peptide, designated CPI-2KR, was designed/synthesized and found to be a more efficient competitive inhibitor of CPR, without affecting the activity of the other plasma carboxypeptidase, carboxypeptidase N. In vitro studies showed that, together with tissue plasminogen activator, CPI-2KR synergistically accelerated fibrinolysis, representing a lead compound for the design of smaller organic molecules for use in thrombolytic therapy.

Amino Acid Sequence↗
PubMed2002

N-glycosylation profile of recombinant human soluble Fcgamma receptor III.

N-glycans of human Fcgamma receptor III (FcgammaR III) are believed to be involved in the interaction with complement receptor type 3 (CR3) (Sehgal et al. [1993] J. Immunol., 150, 4571-4580). Recombinant human soluble FcgammaRIII (rhsFcgammaRIII), which is produced in baby hamster kidney (BHK) cells, has been shown to interact with CR3 in a manner similar to native FcgammaRIII. We elucidated the N-glycosylation profiles of rhsFcgammaRIII by the 3D high-performance liquid chromatography mapping technique. It was revealed that the N-glycans of rhsFcgammaRIII are much more divergent (consisting of 20 neutral, 7 monosialyl, 4 disialyl, 5 trisialyl, and 1 tetrasialyl oligosaccharides) than those previously determined for BHK-expressed mouse sFcgammaRII, notwithstanding close structural similarity of polypeptide chains between the two sFcgammaRs. Particularly, high-mannose type oligosaccharides are specifically expressed on rhsFcgammaRIII.

Animals↗
PubMed2002

[A patient with advanced gastric cancer surviving for more than 5 years after neoadjuvant chemotherapy and curative resection].

The patient was a 54-year-old female who was diagnosed as a Borrmann 4 type gastric cancer with invasion to the descending part of the duodenum and hepatic flexure of the colon. Curative resection was considered to be impossible from the clinical findings, so low-dose CDDP + 5-FU therapy and MTX/5-FU sequential therapy were given. After the chemotherapy, the primary lesion was decreased remarkably and the invasive foci disappeared. Therefore total gastrectomy with perigastric lymphadenectomy and splenic preservation was performed. The histological findings revealed that viable cancer cells remained only in the mucosal layer of the primary lesion. The patient has been alive without recurrence for 66 months after the curative resection. This case report suggests that patients who have good response to neoadjuvant chemotherapy with curative resection appear to have prolonged disease-free and overall survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Apolipoprotein A-I induces translocation of cholesterol, phospholipid, and caveolin-1 to cytosol in rat astrocytes.

Intercellular cholesterol transport in the brain is carried by high density lipoprotein (HDL) generated in situ by cellular interaction with the apolipoprotein apoE, which is mainly synthesized by astrocytes, and with apoA-I secreted by cells such as endothelial cells. Rat astrocytes in fact generate HDL with extracellular apoA-I in addition to releasing HDL with endogenously synthesized apoE, seemingly by the same mechanism as the HDL assembly for systemic circulation. Relating to this reaction, apoA-I induced translocation of newly synthesized cholesterol and phospholipid to the cytosol prior to extracellular assembly of HDL, accompanied by an increase of caveolin-1 in the cytosol, activation of sterol regulatory element-binding protein, and enhancement of cholesterol synthesis. The lipid translocated into the cytosol was recovered in the fraction with a density of 1.09-1.16 g/ml as well as caveolin-1 and cyclophilin A. Cyclosporin A inhibited these apoA-I-mediated reactions and suppressed apoA-I-mediated cholesterol release. The findings suggest that such translocation of cholesterol and phospholipid into the cytosol is related to the apo A-I-mediated HDL assembly in astrocytes through functional association with caveolin-1 and a cyclosporin A-sensitive cyclophilin protein(s).

Animals↗
PubMedDate not supplied

Transition metals and polyol pathway in the development of diabetic neuropathy in rats.

BACKGROUND: The transition metal-catalyzed reaction is a major source of oxygen free radicals, which play an important role in vascular dysfunction leading to ischemia in diabetic tissues. The inhibition of polyol pathway hyperactivity has been reported to ameliorate neurovascular abnormalities in diabetic rats and has been proposed to improve the oxygen free radical scavenging capacity. The present study was conducted to compare the effect of a transition metal chelating agent, trientine (TRI), on diabetic neuropathy with that of an aldose reductase inhibitor, NZ-314 (NZ). METHODS: Diabetic rats were divided into three groups: (1). untreated, (2). TRI-treated, and (3). NZ-treated. TRI (20 mg/kg) or NZ (100 mg/kg) was administered by gavage or chow containing NZ, respectively, for 8 weeks. Motor nerve conduction velocity (MNCV), coefficient of variation of the R - R interval on electrocardiogram (CVr-r), sciatic nerve blood flow (SNBF), platelet aggregation activities, and serum concentrations of malondialdehyde were measured. RESULTS: Untreated diabetic rats showed delayed MNCV, decreased CV(R-R), and reduced SNBF compared to normal rats. TRI or NZ completely prevented these deficits. Platelet hyperaggregation activities in diabetic rats were prevented by NZ, but not by TRI. Increased concentrations of malondialdehyde in diabetic rats were partially but significantly ameliorated by either TRI or NZ. CONCLUSIONS: These observations suggest that increased free radical formation through the transition metal-catalyzed reaction plays an important role in the development of diabetic neuropathy and that the preventive effect of an aldose reductase inhibitor on diabetic neuropathy may also be mediated by decreasing oxygen free radicals.

Aldehyde Reductase↗