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Biomedical subjects

S Okuda

Publications and source records attributed to S Okuda.

At least 19 recordsLinked to original sources

Antioxidants, but not cAMP or high K+, prevent arachidonic acid toxicity on neuronal cultures.

Arachidonic acid (AA) showed profound toxicity against primary neuronal cultures prepared from fetal rat striatum. This toxicity was attenuated by nordihydroguaiaretic acid but not by indomethacin, indicating that lipoxygenase pathway of AA metabolism is involved in the toxicity. Furthermore, the neurotoxic action of AA was abolished by antioxidants butylated hydroxyanisole or N-acetylcysteine. In contrast, treatment with forskolin or high K+, which have been shown to prevent neuronal death induced by MPP+ or high oxygen conditions, showed no protection against AA toxicity. These results suggest that, although oxygen free radicals generated through lipoxygenase metabolism is responsible for the neurotoxicity, distinct mechanisms from those of other oxidative stress are operative in AA-induced neuronal injury.

Animals

Negative-ion fast atom bombardment tandem mass spectrometry for characterization of sulfated unsaturated disaccharides from heparin and heparan sulfate.

Negative-ion fast atom bombardment tandem mass spectrometry has been used in the characterization of non-, mono-, di- and trisulfated disaccharides from heparin and heparan sulfate. The positional isomers of the sulfate group of monosulfated disaccharides were distinguished from each other by negative-ion fast atom bombardment tandem mass spectra, which provide an easy way of identifying the positional isomers. This fast atom bombardment collision induced dissociation mass spectrometry/mass spectrometry technique was also applied successfully to the characterization of di- and trisulfated disaccharides.

Carbohydrate Sequence

The effect of azelastin hydrochloride on pruritus and leukotriene B4 in hemodialysis patients.

Pruritus is a very common complication in chronic hemodialysis (HD) patients, however the exact mechanism for this affliction is still not known. Anti-histaminics usually failed to alleviate uremic pruritus. In others, an anti-allergic drug, which inhibits the release of chemical mediators, such as leukotrienes or histamine from mast cells, was reported to be effective. We evaluated the values of leukotriene B4 and interleukin 6 in HD patients with pruritus and the effect of an anti-allergic drug on these factors. Leukotriene B4, interleukin-6, C3a, C5a, the number of eosinophil and IgE at 0, 15 and 180 minutes after the start of regular HD in 11 HD patients suffering from pruritus and as well as in 11 HD patients without pruritus were examined. These HD patients in both groups showed significantly higher (p < 0.001) values of leukotriene B4 and C3a compared to healthy non-HD subjects. There was no difference in the leukotriene B4, interleukin-6, IgE, C3a and C5a levels between the patients with and without pruritus. Two mg/day of azelastin hydrochloride, an anti-allergic drug was orally given to the pruritus group for 3 weeks. In 5 of 11 patients, the pruritus symptoms disappeared, while in 4 of 11 they improved. Independent of the effect of the drug on pruritus, leukotriene B4 levels significantly decreased compared with those before the administration of this drug in the pruritus group (p < 0.01). Interleukin 6, C3a, C5a and the number of eosinophils demonstrated no significant change. In conclusion, although azelastin hydrochloride was effective in treating pruritus and also suppressed leukotriene B4 levels in hemodialysis patients, the high leukotriene B4 activity itself did not seem to be related to the development of pruritus in these patients.

Histamine Antagonists

Localization of transforming growth factor-beta and latent transforming growth factor-beta binding protein in rat kidney.

TGF-beta plays an important role in maintaining the renal histological structure, and glomerular and tubular function. TGF-beta is usually secreted in a biologically inactive or latent form with high molecular weight by normal cells. The latent form of TGF-beta is composed of three distinct components: (a) mature TGF-beta (b) TGF-beta latency associated peptide (LAP) (c) latent TGF-beta binding protein (LTBP). LTBP plays a central role in the assembly, secretion and activation of TGF-beta 1. Most cells secrete a large latent TGF-beta with LTBP, while the other cells secrete a small latent TGF-beta without LTBP. However, the precise localization of TGF-beta and LTBP in the kidney is still not known. In the present study, we used the reverse transcription in combination with polymerase chain reaction (RT-PCR) to investigate the precise localization of TGF-beta 1 and LTBP in the microdissected glomeruli, renal tubules and arterioles. Our findings showed that TGF-beta 1 mRNA was detected in all nephron segments, glomeruli, and arterioles. On the other hand, LTBP mRNA was present in the glomeruli and arterioles, while it was absent in every segment of the renal tubules. Moreover, the immunohistochemical study of LTBP showed that the LTBP protein was localized on the glomeruli and arterioles but not on the renal tubules at the same localization as LTBP mRNA. These results indicate that the tubular epithelial cells secrete the small latent TGF-beta 1, while glomerular cells secrete the large latent TGF-beta 1, suggesting that they both have different structures and thus potentially different biological functions.

Animals

Isolation and identification of adenosine triphosphoribosyl nicotinamide adenine dinucleotidephosphate from Azotobacter vinelandii.

A novel type of pyridine nucleotide, containing two adenosine triphosphate ribose residues rather than one, was isolated from Azotobacter vinelandii strain O. The nucleotide was shown to be 2"- or 3"-(2'-phosphoadenosine-5'-diphosphoribosyl)nicotinamide adenine dinucleotide phosphate, in which 2'-phospho-5'-diphosphoadenosylribose was glycosidically linked to the NADP at position 2' or 3' of the nicotinamide mononucleotide moiety. The ATPribosylNADP did not show coenzyme activity for yeast glucose 6-phosphate dehydrogenase, nor was it cleaved by Neurospora crassa NAD(P) glycohydrolase, indicating that the biological properties conferred on the beta-NADP molecule were largely modified by the attachment of the ATP-ribose group.

Adenosine Triphosphate

[Growth factors in tubular cells].

Tubular cells are a major source of growth factors in the kidney, while the growth factors may play a crucial role for maintaining the histological structure or functions of renal tubulus. EGF, IGF-1 and HGF are important for the development of tubular segment, renal hypertrophy, regeneration after acute tubular necrosis and renal cyst formation. In contrast, TGF-beta is closely related to tubulo interstitial fibrosis. Since the tubulo interstitial lesions determine the progression or prognosis of the renal diseases, the regulation of these growth factors may be needed for the prevention of the irreversible tubular injury or for the regeneration of tubular cells.

Animals

Matrix-associated latent TGF-beta with latent TGF-beta binding protein in the progressive process in adriamycin-induced nephropathy.

BACKGROUND: A progressive increase in latent transforming growth factor-beta (TGF-beta) secretion from diseased tissue was revealed in our previous work using adriamycin (ADR)-nephropathy (Kidney Int 45:525-36, 1994). Latent TGF-beta is composed of mature TGF-beta and latency-associated peptide (LAP) with or without latent TGF-beta-binding protein (LTBP). LTBP has been reported to contribute to either matrix-association or activation of latent TGF-beta. LTBP also seems to play a key role in the renal lesions of this model. The present study was designed to show the secretion of latent TGF-beta with LTBP and the location of LTBP in renal tissue in ADR-nephropathy. EXPERIMENTAL DESIGN: The renal cortical tissue specimens were sampled at Weeks 4, 8, and 16 after the injection of ADR or saline (control) for cortical tissue culture and immunohistology. TGF-beta in the conditioned medium was assayed by immunoprecipitation and bioassay using mink lung epithelial cells. An immunohistochemical study was performed to examine the localization of LTBP, ED-1-positive macrophages, and extracellular matrix proteins including laminin, fibronectin, and collagen type I and type III. RESULTS: A TGF-beta bioassay revealed a progressive increase in latent TGF-beta secretion from the cortex of diseased kidney. Free LTBP and LTBP-LAP complex with mature TGF-beta were immunoprecipitated by anti-LTBP Ab from the cortical culture medium. An immunohistochemical study using anti-LTBP Ab demonstrated that LTBP localization was restricted to the glomeruli and the arterioles in the control cortex. In the ADR rats at Week 4, a faint deposition of LTBP was observed in the interstitium around the glomeruli. At Week 8 or 16, LTBP was accumulated in the sclerosing glomeruli or fibrous interstitium, where ECM proteins and infiltrating ED-1-positive macrophages were intensely located. CONCLUSIONS: Our results indicated that latent TGF-beta with LTBP was localized in association with the extracellular matrix in the sclerotic and fibrotic tissue in this model. Matrix-associated latent TGF-beta with LTBP may thus play an important role in the progressive process of glomerulosclerosis and interstitial fibrosis in ADR-nephropathy.

Animals

Ameliorative effects of tea catechins on active oxygen-related nerve cell injuries.

Active oxygen species are suggested to be concerned with various senile disorders. Tea catechins, (+)catechin (CA), (-)epicatechin (EC) and (-)epigallocatechin gallate, are polyhydroxy-fravan derivatives from tea leaves and have been proposed to possess active oxygen scavenging effect. Tea catechins protected the cultured newborn-mouse cerebral nerve cells from death induced by glucose oxidase. The protective potency of (-)epigallocatechin gallate was weaker than those of EC and CA. Learning ability of mice was assessed by a step-down-type passive avoidance test, and memory impairment of mice was achieved by intracisternal injection of glucose oxidase or cerebral ischemia induced by 10 min occlusion of the common carotid arteries. Intracisternal injection of EC improved the memory impairment induced by intracisternal glucose oxidase, and i.v. injection of CA or EC improved that induced by the cerebral ischemia. CA and EC depressed carrageenin-induced edema in rat hind paw, but (-)epigallocatechin gallate did not. These results suggest that tea catechins ameliorate the injuries or impairments induced by active oxygens through scavenging intracellular active oxygens, and might become useful for protecting human from senile disorders such as dementia.

Animals

Tandem mass spectrometry for characterization of unsaturated disaccharides from chondroitin sulfate, dermatan sulfate and hyaluronan.

Fast atom bombardment tandem mass spectrometry has been used in the characterization of non-, mono-, di- and trisulfated disaccharides from chondroitin sulfate, dermatan sulfate and hyaluronan. The positional isomers of the sulfate group of mono- and disulfated disaccharides were distinguished from each other by both positive- and negative-ion fast atom bombardment tandem mass spectra, which gave sufficient information characteristic of the isomers. The anomeric isomers of nonsulfated disaccharides were characterized by the technique in the positive-ion mode. This fast atom bombardment collision induced dissociation mass spectrometry/mass spectrometry technique was also applied successfully to the characterization of trisulfated disaccharide.

Carbohydrate Conformation

Two cases of urogenital malignancies in male patients undergoing maintenance haemodialysis.

We report two cases of urogenital malignancies, prostatic cancer in a 72-year-old man and urinary bladder carcinoma in a 50-year-old man, that developed during maintenance haemodialysis. The former patient responded to hormonal therapy with diethylstilboestrol and is still alive on maintenance haemodialysis, but the latter patient did not respond to treatment, being past cure in the far advanced stage. There are few clinical symptoms suggesting the existence of urogenital malignancies in dialysis patients and screening methods such as urine cytology or roentgenology must be restricted because of extremely reduced urine volume. However, the high incidence of urogenital malignancies in such patients is well recognized. Screening examinations with ultrasonography and/or CT scan following digital rectal examination or testing for serum prostate-specific antigen should be performed at least every 6 months.

Aged

Increased expression of Na+/H+ exchanger in the injured renal tissues of focal glomerulosclerosis in rats.

The renal mRNA expression of Na+/H+ exchanger (NHE) and the effects of NHE inhibitor, amiloride, on renal injury were investigated in adriamycin (ADR)-induced glomerulosclerosis model in rats, which progressively developed extensive glomerulosclerosis and interstitial fibrosis. NHE-1 mRNA from the cortex of the ADR rats progressively increased at weeks 4 and 8 and then peaked at week 16, which paralleled with the degree of glomerular sclerosis and interstitial fibrosis. The interstitial fibrosis in the ADR-rats was prevented by a daily administration of amiloride. A simultaneous analysis of the effects of a high salt diet on NHE-1 mRNA expression or renal injury was performed in the ADR rats at weeks 2 and 8. Renal or glomerular hypertrophy was observed in the control or ADR rats fed an 8% NaCl diet at week 2 and 8 compared to a 1% NaCl diet, while the NHE-1 mRNA expression was not up-regulated by an 8% NaCl diet at week 2. At week 8, the NHE-1 mRNA expression or glomerulosclerosis and interstitial fibrosis were enhanced in the ADR rats fed an 8% NaCl diet compared to a 1% NaCl diet. This histological aggravation by an 8% NaCl diet was prevented by a daily administration of amiloride but not by furosemide. In conclusion, the increased NHE-1 mRNA expression and the preventive effects of amiloride on the renal lesions suggest a potential importance of NHE in the progressive process of ADR-nephropathy. The high salt diet had a hypertrophic and destructive effect on kidney or glomeruli in the ADR rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride

Cytologic examination of pure pancreatic juice in the diagnosis of pancreatic carcinoma. The endoscopic retrograde intraductal catheter aspiration cytologic technique.

BACKGROUND: Although cytologic examination of pure pancreatic juice obtained with a duodenofiberscope has been useful for the diagnosis of pancreatic carcinoma, the rate of false-negative results is reported to be high. To eliminate these false-negative results, the authors developed a new technique, endoscopic retrograde intraductal catheter aspiration cytology, especially for an accurate cytologic diagnosis of carcinoma of the body or tail of the pancreas. METHODS: The accuracy of conventional cytologic examination of pure pancreatic juice was assessed in 25 patients with pancreatic carcinoma, 29 patients with pancreatitis, and 52 control subjects. Pure pancreatic juice was collected from the pancreatic duct by endoscopic cannulation using a videoimaging duodenoscope after intravenous administration of secretin. The new endoscopic retrograde intraductal catheter aspiration technique was used in four patients with carcinoma of the body or tail of the pancreas and five patients with localized pancreatitis in whom a correct diagnosis was not made by previous cytologic examination of pure pancreatic juice. RESULTS: Positive cytologic findings were obtained in 76% of the patients with pancreatic carcinoma. Positive cytologic results were more frequent in patients with carcinoma of the head of the pancreas than in those with carcinoma of the body or tail. By the new technique, positive cytologic results were obtained in all of the patients with pancreatic carcinoma. This technique caused no severe complications. CONCLUSIONS: This procedure of endoscopic retrograde intraductal catheter aspiration cytology seems useful for diagnosis of pancreatic carcinoma.

Catheterization

Measurement of glycated albumin by the nitroblue tetrazolium colorimetric method.

A method has been developed for the measurement of glycated albumin (albumin-fructosamine) by the nitroblue tetrazolium (NBT) colorimetric method. In this method, polyethylene glycol was added to the serum and then the mixture was centrifuged to separate globulin proteins from albumin proteins. This made it possible to measure the glycated albumin in the supernatant by the NBT colorimetric method, without the interference of globulin proteins. This measurement method correlated with the measurement of glycated albumin using boronate affinity chromatography with an r value of 0.942 (P < 0.001). Our method using polyethylene glycol permits easy measurement of albumin fructosamine and is therefore useful as an index of diabetic control and for diabetic screening.

Chromatography, Affinity

Early depressed adenocarcinomas of the large intestine.

From January 1987 to December 1990, five cases of early depressed cancer of the large intestine were seen. Endoscopically, almost all of these tumors were located in the proximal colon and looked like a reddish depression (similar to the sucker of an octopus). Histologically, all of these cancers were well differentiated and tended to reach deeper layers at an early stage. Four (80%) of these cancers were not associated with adenoma and were thought to have arisen de novo.

Adenocarcinoma

Enhancement by thyroxine of experimental carcinogenesis induced in rat colon by azoxymethane.

The effect of thyroxine (T4) on the incidence, number and histology of colon tumors induced by azoxymethane (AOM), and on the labeling index of colon mucosa were investigated in Wistar rats. Rats were given AOM by injection once a week for 10 weeks, together with T4 in depot form until the end of the experiment. Administration of T4 resulted in a significant increase in the incidence of colon tumors in week 35. However, it did not influence the histological appearance of the colon tumors or the histological types and depths of involvement of colon adenocarcinomas. Furthermore, it caused a significant increase in the labeling index of the colon during, but not after, AOM treatment. Our findings indicate that T4 enhances the development of colon tumors, which may be related to its effect in increasing proliferation of epithelial cells in the colon mucosa during administration of the carcinogen.

Adenocarcinoma