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Biomedical subjects

K Uchida

Publications and source records attributed to K Uchida.

At least 379 records · Page 21Linked to original sources
PubMed1999

17beta-estradiol induces protein thiol/disulfide oxidoreductases and protects cultured bovine aortic endothelial cells from oxidative stress.

OBJECTIVE: To examine whether or not estrogens induced the expression of protein thiol/disulfide oxidoreductases such as protein disulfide isomerase (PDI), thioredoxin (Trx), Trx reductase, and glutaredoxin (Grx) in vascular endothelial cells. METHODS: The regenerative effects of the protein thiol/disulfide oxidoreductases, PDI, Trx and Grx, on oxidatively damaged proteins were assayed using H2O2-inactivated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a reporter enzyme. The induction of protein thiol/disulfide oxidoreductases and the accumulation of protein adducts generated by lipid peroxidation were examined by Western blotting in estrogen-treated bovine aortic endothelial cells (BAECs). RESULTS: Reduced PDI, Trx and Grx regenerated the H2O2-inactivated GAPDH in vitro. The levels of these protein disulfide oxidoreductases in BAECs were increased by pretreatment with 0.01-10 micromol/l 17beta-estradiol, the largest increase (about fourfold of the control) being found for PDI. Other sex hormones such as progesterone and testosterone did not affect the contents of these oxidoreductases in BAECs. 4-Hydroxy-2-nonenal (HNE)-protein adducts, which are generated by lipid peroxidation, were accumulated in BAECs exposed to paraquat, whereas the pretreatment of BAECs with 17beta-estradiol suppressed their accumulation. CONCLUSIONS: The estrogen-mediated induction of the protein thiol/disulfide oxidoreductases such as PDI, Trx, Trx reductase and Grx suggested a possible involvement of these oxidoreductases in the antioxidant protection of estrogen observed in the vascular system.

Animals↗
PubMed1999

Immunohistochemical evidence for an increased oxidative stress and carbonyl modification of proteins in diabetic glomerular lesions.

Advanced glycation end products (AGE) include a variety of protein adducts whose accumulation has been implicated in tissue damage associated with diabetic nephropathy (DN). It was recently demonstrated that among AGE, glycoxidation products, whose formation is closely linked to oxidation, such as carboxymethyllysine (CML) and pentosidine, accumulate in expanded mesangial matrix and nodular lesions in DN, in colocalization with malondialdehyde-lysine (MDA-lysine), a lipoxidation product, whereas pyrraline, another AGE structure whose deposition is rather independent from oxidative stress, was not found within diabetic glomeruli. Because CML, pentosidine, and MDA-lysine are all formed under oxidative stress by carbonyl amine chemistry between protein amino group and carbonyl compounds, their colocalization suggests a local oxidative stress and increased protein carbonyl modification in diabetic glomerular lesions. To address this hypothesis, human renal tissues from patients with DN or IgA nephropathy were examined with specific antibodies to characterize most, if not all, carbonyl modifications of proteins by autoxidation products of carbohydrates, lipids, and amino acids: CML (derived from carbohydrates, lipids, and amino acid), pentosidine (derived from carbohydrates), MDA-lysine (derived from lipids), 4-hydroxynonenal-protein adduct (derived from lipids), and acrolein-protein adduct (derived from lipids and amino acid). All of the protein adducts were identified in expanded mesangial matrix and nodular lesions in DN. In IgA nephropathy, another primary glomerular disease leading to end-stage renal failure, despite positive staining for MDA-lysine and 4-hydroxynonenal-protein adduct in the expanded mesangial area, CML, pentosidine, and acrolein-protein adduct immunoreactivities were only faint in glomeruli. These data suggest a broad derangement in nonenzymatic biochemistry in diabetic glomerular lesions, and implicate an increased local oxidative stress and carbonyl modification of proteins in diabetic glomerular tissue damage ("carbonyl stress").

Adult↗
PubMed1999

Effect of histamine H2-receptor antagonist on the phosphorus-binding abilities of calcium carbonate and calcium lactate in hemodialysis patients.

The effect of histamine H2-receptor antagonist (famotidine) on the phosphorus-binding abilities of calcium carbonate and calcium lactate were examined in 13 chronic hemodialysis patients. In seven patients receiving calcium carbonate, famotidine (20 mg/d) was given because of gastroduodenal disorders, and calcium carbonate was replaced with calcium lactate as a phosphorus binder after 4 wk of treatment with famotidine. With the 4-wk administration of famotidine accompanied by calcium carbonate, the serum phosphorus level increased from 6.3+/-0.9 to 7.1+/-0.5 mg/dl (P<0.05). However, with the substitution of calcium lactate, the serum phosphorus level decreased significantly when compared to that before substitution (6.3+/-0.2 and 6.0+/-0.9 mg/dl after 4 and 8 wk of substitution, respectively), despite continued administration of famotidine. Serum calcium, creatinine, alkaline phosphatase, high sensitive parathyroid hormone, blood urea nitrogen, arterial blood pH, and bicarbonate were not significantly altered during the trial period. In six control patients treated with calcium carbonate alone, there were no statistical changes in serum calcium and phosphorus levels after substitution of calcium lactate for calcium carbonate. These results suggest that famotidine significantly affects the phosphorus-binding ability of calcium carbonate, but not that of calcium lactate. A careful observation of changes in the serum phosphorus level should be required in hemodialysis patients receiving calcium carbonate and histamine H2-receptor antagonists. Calcium lactate may be useful as a phosphorus binder in such hemodialysis patients.

Adult↗
PubMed1999

Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats, a model of type 2 diabetes.

Reactive oxygen species are involved in a diversity of biological phenomena such as inflammation, carcinogenesis, aging, and atherosclerosis. We and other investigators have shown that the level of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker for oxidative stress, is increased in either the urine or the mononuclear cells of the blood of type 2 diabetic patients. However, the association between type 2 diabetes and oxidative stress in the pancreatic beta-cells has not been previously described. We measured the levels of 8-OHdG and 4-hydroxy-2-nonenal (HNE)-modified proteins in the pancreatic beta-cells of GK rats, a model of nonobese type 2 diabetes. Quantitative immunohistochemical analyses with specific antibodies revealed higher levels of 8-OHdG and HNE-modified proteins in the pancreatic beta-cells of GK rats than in the control Wistar rats, with the levels increasing proportionally with age and fibrosis of the pancreatic islets. We further investigated whether the levels of 8-OHdG and HNE-modified proteins would be modified in the pancreatic beta-cells of GK rats fed with 30% sucrose solution or 50 ppm of voglibose (alpha-glucosidase inhibitor). In the GK rats, the levels of 8-OHdG and HNE-modified proteins, as well as islet fibrosis, were increased by sucrose treatment but reduced by voglibose treatment. These results indicate that the pancreatic beta-cells of GK rats are oxidatively stressed, and that chronic hyperglycemia might be responsible for the oxidative stress observed in the pancreatic beta-cells.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

[Taxonomy of genus Malassezia: progress and problems].

The genus Malassezia is composed of lipophilic basidiomycetous yeasts which were recently shown to consist of seven species, one lipid-independent species, M. pachydermatis and six lipid-dependent species, M. furfur, M. sympodialis, M. globosa, M. obtusa, M. restricta and M. slooffiae. Based on this classification, we will be able to analyze pathogenicity or relationship between Malassezia-related diseases and each species.

Malassezia↗
PubMed1999

[The expression of thymidylate synthase and thymidine phosphorylase in the early-stage of gastric cancer].

The immunohistochemical expression of thymidylate synthase (TS) and thymidine phosphorylase (TP) was investigated in 116 of early gastric cancer, in order to know whether or not these reflect malignity in an early stage. The materials conditioned on early gastric cancer with submucosal invasion and over 1 cm2 in size, were 57 with and 59 without lymph node metastasis. They were divided into two by the depth of invasion. The expressions of TS and TP in these group were compared with corresponding histopathological findings. Overall expressions of TS and TP were 54.3% and 34.5%, respectively. The TS-expression was not related with the depth of invasion and lymph node metastasis. The TP-expression, however, showed significant difference between with and without lymph node metastasis, and was so on the depth of submucosal invasion in the group without the nodal metastasis. Multivariate analysis showed that mucosal spread bordering 4 cm2 in size (p = 0.024) and lymphatic permeation (p = 0.099) in TS-expression, and lymph node metastasis (p = 0.041), submucosal invasion (p = 0.076) and venous permeation (p = 0.111) in TP-expression were the noticeable factors regarding to their high expression rates. Although these results were considered not to exceed gastric resection on the prognosis, they might be applicable as one of the indicators in postoperative follow-up on the minor resection of early gastric cancer such as EMR or local resection.

Female↗
PubMed1999

[Therapeutic efficacy of a topical antifungal solution preparation formulated with pyrrolnitrin and clotrimazole in combination (Pyroace W) in guinea pig model of tinea pedis].

The therapeutic efficacy of a topical antifungal solution containing a mixture of 0.2% pyrrolnitrin and 0.4% clotrimazole (Pyroace W) was tested in a guinea pig model of tinea pedis using a 1% newly solution formulated preparation of miconazole (Dermalin-L) as a reference drug. Infected animals were treated once or twice daily with the testing drug and once daily with the reference drug for 4 weeks. Therapeutic efficacy was evaluated on the basis of the extent of the yield of fungal cultures from the infected skin tissues (infection intensity) and the relative number of culture-negative animals at the end of the treatment period. In an animal group treated once daily with the testing drug, the infection intensity was significantly lower than that for untreated or vehicle-treated control group (p < 0.0001) although there was no culture-negative animal. A similar extent of therapeutic efficacy was obtained with a once daily treatment with the reference drug, yielding one of ten culture-negative animal. A better efficacy was seen in animals treated twice daily with the testing drug; the infection intensity was further decreased to a significant level and eight of ten animals became culture-negative. These results demonstrated that twice daily treatment with the testing drug was highly effective in guinea pig model of tinea pedis, 80% of infected animals being mycologically cured. It confirms the clinical usefulness of this regimen in the treatment of patients with tinea pedis or other types of dermatophytosis.

Animals↗
PubMed1999

[The maximum safe dosage of the low molecular weight hydroxyethyl starch, HESPANDAR (HES), estimated from HES induced changes in coagulation parameters and clinical bleeding].

The effects of hydroxyethyl starch on the coagulation system have received attention, and safe dosage of high molecular weight hydroxyethyl starch is generally found to be 20 ml.kg-1. Low molecular weight hydroxyethyl starch, HESPANDAR (HES), seems to induce weaker specific effects on blood coagulation than high molecular weight hydroxyethyl starch. The aims of this study are to estimate the maximum safe dosage of HES, and to investigate the etiology for coagulopathy induced by HES. Forty three patients (18 to 75 years old) who were free of bleeding disorders scheduled for abdominal operations received 20, 30, or 40 ml.kg-1 of HES. We measured coagulation parameters of them including platelet, hematocrit, total protein, activated partial thromboplastin time, prothrombin time and Factor 8, and observed the evidence of clinical microbleeding. As the HES was infused, the values of coagulation parameters except Factor 8 changed with blood dilution. Factor 8 decreased more than expected from the values calculated for hemodilution. The evidences of clinical microbleeding were observed when patients had received HES more than 30 ml.kg-1. The decrease of Factor 8 and the observed tendency of clinical microbleeding showed a significant positive relationship (P = 0.0002). We conclude from our results that the maximum safe dosage of HES is about 30 ml.kg-1, and HES may affect blood coagulation by lowering the plasma concentration of Factor 8.

Abdomen↗
PubMed1999

[The in vitro properties of a new hydroxypyridone antimycotic rilopirox, with special reference to its anti-Candida activity].

In vitro properties of a new hydroxypyridone antimycotic rilopirox (RIL) with special reference to its anti-Candida activities were studied in comparison with the three reference drugs, ciclopirox olamine (CPO), oxiconazole nitrate (OCZ) and isoconazole nitrate (ICZ), using several strains of Candida albicans and Candida glabrata as the test organisms. RIL was potently fungicidal for growing cultures of these Candida strains, whereas all the three reference drugs were slightly fungicidal or fungistatic. Unlike OCZ and ICZ whose anti-Candida activity was decreased by lowering pH or adding serum to culture media, the activity of RIL was scarecely affected by change in pH or serum addition. However, RIL became less potent in the presence of Fe3+ at concentrations of 10(-5) mmol/ml or above. These findings suggest that RIL will be useful as a topical anti-Candida agent.

Antifungal Agents↗
PubMed1999

Functional analysis of poly(ADP-ribose) polymerase in Drosophila melanogaster.

Poly(ADP-ribose) polymerase (PARP) is conserved in eukaryotes. To analyze the function of PARP, we isolated and characterized the gene for PARP in Drosophila melanogaster. The PARP gene consisted of six translatable exons and spanned more than 50 kb. The DNA binding domain is encoded by exons 1-4. Although the consensus cleavage site of CED-3 like protease during apoptosis is conserved from human to Xenopus laevis PARPs, it is neither conserved in the corresponding region of Drosophila nor Sarcophaga peregrina. There are two cDNAs species in Drosophila. One cDNA could encode the full length PARP protein (PARP I), while the other is a truncated cDNA which could encode a partial-length PARP protein (PARP II), which lacks the automodification domain and is possibly produced by alternative splicing. The expression of these two forms of PARP in E. coli demonstrated that while PARP II has the catalytic NAD-binding domain and DNA-binding domain it is enzymatically inactive. On the other hand PARP I is active. A deletion mutant of PARP gene could grow to the end of embryogenesis but did not grow to the adult fly. These results suggest that the PARP gene plays an important function during the development of Drosophila.

Animals↗
PubMed1999

Effects of high temperature on the emergence and survival of adult Culex pipiens molestus and Culex quinquefasciatus in Japan.

The emergence rate and adult survival (longevity) of Japanese strains of Culex pipiens molestus and Culex quinquefasciatus were compared at temperatures of 21, 25, and 30 degrees C. The pupation and emergence rates in both strains were higher at 21 and 25 degrees C than at 30 degrees C. The adult emergence rate, especially in females, was lower in Cx. p. molestus than in Cx. quinquefasciatus. Longevity of females and males was lower in Cx. p. molestus at 25 degrees C and above. The survival of Cx. p. molestus was adversely affected by temperatures of 28 degrees C and higher. High temperature may restrict the distribution of this species. Therefore, if Cx. p. molestus infests the Okinawa region, the likelihood that it will become established is minimal.

Animals↗
PubMed1999

[Clinical outcome of emergency coronary artery bypass grafting for acute myocardial infarction with cardiogenic shock].

From January 1993 through December 1998, Emergency Coronary Artery Bypass Grafting was Performed within 24 Hours after the Onset of Acute Myocardial Infarction (AMI) with Cardiogenic Shock in 22 Patients (17 men and 5 women; aged, 52-81 years). The incidence of AMI involving the left main coronary artery was 50%. The incidence of interventional therapy was 40.9% (PTCA 31.8%; PTCR 9.1%). The condition in 95.5% of the patients could be stabilized hemodynamically by preoperative intraaortic balloon pumping; 4 of the 5 patients suffered from cardiopulmonary arrest required percutaneous cardiopulmonary support. There were 4 (18.2%) deaths overall. Operative mortality was related to the intervals between AMI and operation (less than 6 hours, 25%; 6 to 24 hours, 10%). Three of the 4 patients who received cardiopulmonary support survived. We conclude that early revascularization and minimal reperfusion injury caused by mechanical devices are important determinants of survival in patients who have AMI with cardiogenic shock.

Aged↗
PubMed1999

Increased serum levels of vascular endothelial growth factor in human crescentic glomerulonephritis.

OBJECTIVE: To investigate the serum levels of vascular endothelial growth factor (VEGF) in human crescentic glomerulonephritis (CRGN). METHODS: The serum VEGF levels in CRGN patients were compared with those in healthy subjects and in various types of glomerulonephritis. In addition, we investigated the relationship between serum VEGF levels and creatinine levels (Scr) and pathological parameters. RESULTS: The serum VEGF levels of the CRGN patients were significantly higher than in the healthy subjects and patients with MCNS, IgAN, and FGS. No correlation was found between serum VEGF levels and Scr in the RPGN patients. The serum VEGF levels in 6 CRGN patients had significantly decreased after 6 months of corticosteroid therapy. Moreover, there was a significant correlation between the serum VEGF levels and the crescent frequency or the grade of interstitial injury, and the rates of glomerular infiltration by macrophages. CONCLUSIONS: In the CRGN patients, severe glomerular and interstitial damages would result in increased serum VEGF levels and corticosteroid therapy may exert its efficacy through reduction of serum VEGF levels.

Adrenal Cortex Hormones↗
PubMed1999

Gains of 1q21-q22 and 13q12-q14 are potential indicators for resistance to cisplatin-based chemotherapy in ovarian cancer patients.

The mechanism of drug resistance in ovarian cancer is multifactorial, and accumulation of multiple genetic changes may lead to the drug-resistant phenotype. In our attempt to find characteristic genetic changes in drug-resistant tumors, we screened the whole genome for gene aberrations in 28 primary ovarian cancers using the comparative genomic hybridization method. These cancers included 14 tumors from patients who did not respond to cisplatin-based combination chemotherapy and 14 tumors from patients who had complete response to the chemotherapy. We found gains in chromosomal regions 1q21-q22 and 13q12-q14 to be related to the drug-resistant phenotype in ovarian cancer patients. Several genes encoding transcription factors, oncogenes, cell cycle regulators, and regulators of the apoptotic pathway are located on these regions of the chromosomes, and these genes are potential modulators for toxic insults in cancer cells. This is the first report that shows the relationship between certain genomic aberrations and clinical resistance to cisplatin-based chemotherapy in ovarian cancer patients based on the comparative genomic hybridization analysis. Present findings suggest that these chromosomal gains may be potential indicators for prediction of resistance in ovarian cancer patients before cisplatin-based chemotherapy.

Antineoplastic Agents↗