Search PubMed⌕ Search

Biomedical subjects

K Okada

Publications and source records attributed to K Okada.

At least 127 records · Page 7Linked to original sources

Curcumin and especially tetrahydrocurcumin ameliorate oxidative stress-induced renal injury in mice.

Protective effects of curcumin (U1), one of the major yellow pigments in turmeric and its derivative, tetrahydrocurcumin (THU1), against ferric nitrilotriacetate (Fe-NTA)-induced oxidative renal damage were studied in male ddY mice. Single Fe-NTA treatment (5 mg Fe/kg body intraperitoneally) transiently causes oxidative stress, as shown by the accumulation of lipid peroxidation products and 8-hydroxy-2'-deoxyguanosine in the kidney. Mice were fed with a diet containing 0.5 g/100 g U1 or THU1 for 4 wk. THU1 significantly inhibited 2-thiobarbituric acid reactive substances and 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2'-deoxyguanosine formation in the kidney; U1 inhibited only 4-hydroxy-2-nonenal-modified protein formation. To elucidate the mechanisms of protection by U1 and THU1, the pharmacokinetics and radical-scavenging capacities of U1 and THU1 were investigated by HPLC and electron spin resonance spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide, respectively. Induction of antioxidant enzymes was also investigated. The amounts of THU1 and its conjugates (as sulfates and glucuronides) in the liver and serum were larger in the THU1 group than in the U1 group. The amounts of U1 and its conjugates were small even in the U1 group. These results suggest that THU1 is more easily absorbed from the gastrointestinal tract than U1. Furthermore, THU1 induced antioxidant enzymes, such as glutathione peroxidase, glutathione S-transferase and NADPH: quinone reductase, as well as or better than U1 and scavenged Fe-NTA-induced free radicals in vitro better than U1. These results suggest that U1 is converted to THU1 in vivo and that THU1 is a more promising chemopreventive agent.

Animals↗

Intravascular ultrasound imaging before and after angioplasty for stenosis of arteriovenous fistulae in haemodialysis patients.

BACKGROUND: Complications of haemodialysis vascular access have emerged as a major cause of patient morbidity. Intravascular ultrasound imaging is a new technical modality providing visualization of the vessel lumen and wall structure in a cross-sectional fashion. Percutaneous transluminal angioplasty has long been used in the treatment of stenoses of arteriovenous fistulae. However, there is no detailed quantitative information on the stenotic lesion and the morphological change by angioplasty. METHODS: Intravascular ultrasound studies were performed in 40 haemodialysis patients with 63 stenoses in arteriovenous fistulae who had percutaneous transluminal angioplasty. The patients were qualitatively and quantitatively evaluated for echogenic patterns and morphological changes before and after angioplasty. RESULTS: Morphological plaque features in stenotic lesions were classified as 37 soft (58%), five hard (8%), 20 mixed (32%), and one calcified sites. Plaque fractures after angioplasty were detected in 45/63 (71%) instances. The lumen cross-sectional area was found to be dilated approximately threefold (from 3.8+/-2.4 to 11.1+/-4.5 mm(2)) and the external elastic membrane cross-sectional area was dilated approximately twofold (from 11.1+/-5.3 to 19.8+/-8.1 mm(2)) after angioplasty. CONCLUSION: These results indicate that intravascular ultrasound allows both qualitative and quantitative assessments of arteriovenous fistulae in haemodialysis patients. The results further suggest that the mechanism of expansion of arteriovenous fistulae stenoses by percutaneous transluminal angioplasty involves stretching of the vessel wall as well as plaque fractures.

Adult↗

Erythropoietin modulates angiotensin II- or noradrenaline-induced Ca(2+) mobilization in cultured rat vascular smooth-muscle cells.

BACKGROUND: It has been reported that human recombinant erythropoietin (rHuEpo) modulates the sensitivity of the cardiovascular system to angiotensin II (Ang II) or noradrenaline (NA). In the present study, we explored the effect of rHuEpo on the responsiveness of Ang II- or NA-induced cytosolic free calcium ([Ca(2+)]i) mobilization in cultured rat vascular smooth-muscle cells (VSMC). METHODS: [Ca(2+)]i concentrations in VSMC were measured by using the calcium-sensitive fluorescent dye fura-2. RESULTS: The addition of rHuEpo (250 U/ml) alone induced elevation in [Ca(2+)]i, which remained significantly elevated above basal level for at least 60 min in the presence of extracellular Ca(2+). Pre-incubation with specific protein kinase C (PKC) inhibitor calphostin C (1 micromol/l) significantly reduced the peak and the sustained elevations of [Ca(2+)]i. Pre-treatment with rHuEpo for 60 min increased both basal [Ca(2+)]i and the changes in [Ca(2+)]i by Ang II or NA in a dose-dependent manner in the presence of extracellular Ca(2+). The synergistic effects of rHuEpo with Ang II or NA were also retained when VSMC were bathed in the Ca(2+)-free medium after the pre-incubation of rHuEpo. Conversely, they were diminished in the presence of extracellular Ca(2+) combined with intracellular Ca(2+) release inhibitor 8-(NN-diethylamino)octyl-1,3,4,5-trimethoxybenzoate (TMB-8). The synergistic effects of rHuEpo were also diminished by PKC depletion or by PKC inhibitor. CONCLUSIONS: These observations suggest that rHuEpo has synergistic effects on Ang II- or NA-induced [Ca(2+)]i mobilization, particularly on intracellular Ca(2+) release, in VSMC. This may be a potential mechanism contributing to hypertension associated with rHuEpo therapy.

Angiotensin II↗

Subcellular localization and targeting of glucocorticoid receptor protein fusions expressed in transgenic Arabidopsis thaliana.

An animal system of inducible activation of protein fusions with the binding domain of glucocorticoid receptor (BDGR) was tested in Arabidopsis thaliana by monitoring dexamethasone (DEX)-induced nuclear targeting of reporter constructs. Two constructs containing green fluorescent protein (GFP), human homeobox protein Hanf-1 and Xenopus laevis BDGR were used, GFP/Hanf-1/BDGR and GFP/BDGR. The control construct contained GFP alone. In the absence of DEX both fusion proteins were uniformly distributed in the cytoplasm of root cells, but showed strong association with plastids in plant aerial parts. DEX treatment of roots prompted a strong and reversible nuclear accumulation of GFP/Hanf-1/BDGR, but not GFP/BDGR. Thus, in roots, the specific nuclear translocation of GFP/Hanf-1/BDGR was driven by Hanf-1 and tightly regulated by BDGR. However, in plant aerial parts treated with DEX, nuclear translocation of GFP/Hanf-1/BDGR was observed only in a few cases, and most part of the fusion protein was incorrectly and irreversibly targeted to plastids. Protease X digestion of isolated chloroplasts showed that BDGR fusion proteins were translocated into the chloroplast envelope and bound to envelope membranes, probably due to association with the chloroplast import apparatus. Thus, for efficient use of the glucocorticoid-inducible system in plants, it will be necessary to modify BDGR structure to prevent incorrect targeting of fusion proteins.

Animals↗

The relationship between plasma concentration of mature adrenomedullin and jugular venous oxygen saturation during and after cardiopulmonary bypass.

UNLABELLED: Adrenomedullin (AM), a vasodilatory peptide, increases during cardiac surgery. However, the physiological role of AM during cardiac surgery remains unclear. AM dilates cerebral arterioles and increases cerebral blood flow in rats. Therefore, we investigated whether AM is related to cerebral oxygen balance during cardiac surgery. In nine patients undergoing coronary artery bypass grafts, plasma concentrations of mature AM from the radial artery (mAMa) and jugular bulb (mAMj) were measured, and jugular venous oxygen saturation was obtained before surgery (baseline), before aortic cross-clamp (preclamp), after aortic declamp (postclamp), and 20 min after weaning from the cardiopulmonary bypass (post-CPB). Plasma concentrations of mAMa and mAMj were significantly increased at postclamp (P < 0.01 for both) and post-CPB (P < 0.01 for both) compared with baseline values. SjO(2) correlated with plasma mAMj concentrations at preclamp (r = 0.79, P < 0.01), postclamp (r = 0.71, P < 0.05), and post-CPB (r = 0.72, P < 0.05), as well as with mAMa concentrations at preclamp (r = 0.79, P < 0.01) and postclamp (r = 0.72, P < 0.05). This suggests a relationship between AM and cerebral oxygen balance during cardiac surgery. IMPLICATIONS: Plasma concentrations of mature-form adrenomedullin, a vasodilatory peptide, was correlated with jugular venous oxygen saturation during cardiac surgery. This suggests a relationship between adrenomedullin and cerebral oxygen balance during cardiac surgery.

Adrenomedullin↗

Serum uric acid and the risk for hypertension and Type 2 diabetes in Japanese men: The Osaka Health Survey.

OBJECTIVE: To investigate the association of serum uric acid level with the risk for hypertension and Type 2 diabetes. DESIGN: Prospective cohort study. SETTING: Work site in Osaka, Japan. PARTICIPANTS: A total of 6,356 Japanese men, aged 35-60 years with systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg, normal glucose intolerance, and no history of hypertension or diabetes at baseline. MAIN OUTCOME MEASURES: Blood pressure was measured by standard techniques, using 160/95 mmHg for diagnosis of hypertension. Type 2 diabetes was defined as a fasting plasma glucose level > or = 126 mg/dl or a 2 h post-loaded plasma glucose level > or = 200 mg/dl. RESULTS: During the 61,716 person-years follow-up period, we confirmed 639 cases of hypertension and 454 cases of Type 2 diabetes. Serum uric acid level was associated with an increased risk for hypertension but not for Type 2 diabetes. After adjustment for known risk factors, including daily alcohol consumption, the serum uric acid level was associated with an increased risk for hypertension; the relative risks for hypertension were 1.00 for quintile 1 of the serum uric acid level, 1.24 [95% confidence interval (CI), 0.94-1.65] for quintile 2, 1.34 (CI, 1.03-1.76) for quintile 3, 1.76 (CI, 1.35-2.29) for quintile 4, and 2.01 (CI, 1.56-2.60) for quintile 5 (P for trend < 0.001). Even among both non-drinkers and lean subjects, serum uric acid level was associated with an increased risk for hypertension. CONCLUSIONS: Serum uric acid level was associated with an increased risk for hypertension but not for Type 2 diabetes.

Adult↗

FDG PET for evaluating the change of glucose metabolism in prostate cancer after androgen ablation.

In the clinical study of prostate cancer, the effect of androgen ablation on glucose metabolism in cancer tissue has not been elucidated. The purpose of this study was to investigate the change in glucose utilization due to endocrine therapy for prostate adenocarcinoma. Ten patients with histologically proven prostate cancer were prospectively investigated with (18)F-fluorodeoxyglucose and positron emission tomography (FDG PET) prior to and after the initiation of endocrine therapy. FDG uptake was calculated to measure glucose utilization in cancer tissue. The change in FDG accumulation was compared with changes in serum prostate specific antigen (PSA) level and prostate size. FDG accumulation in the prostate decreased in all patients 1-5 months after the initiation of hormone therapy. The serum PSA level and prostate size measured on computerized tomography (CT) also decreased in these periods. A decrease in FDG accumulation was also demonstrated in metastatic sites. In this study, there appeared to be a decrease in FDG uptake in prostate cancer after endocrine therapy not only in primary prostate cancer lesions but also at metastatic sites, suggesting that the glucose utilization by tumours was suppressed by androgen ablation.

Adenocarcinoma↗

Mathematical and optimal clustering of test points of the central 30-degree visual field of glaucoma.

PURPOSE: To determine a mathematically optimal sector pattern of the central 30 degree visual field for the follow-up of glaucomatous visual field change based on a large number of actual visual field test data of patients with glaucoma. METHODS: Visual field test data obtained from 1,039 eyes of 1,039 patients with open-angle glaucoma (OAG) using the 30-2 program of the Humphrey Field Analyzer were used for sectorization of the central 30 degree visual field. Of the 1,039 visual field data, 698 (modeling data) were used for determining the sector pattern and 341 (testing data) for checking the sector pattern. The modeling data were further divided into three groups according to the mean deviation (MD) (MD > or = -10 dB, -20 < or = MD < -10 dB, and MD < -20 dB), and the sector pattern was constructed from visual field data of each group using a clustering procedure called VARCLUS. The testing data were used for determining the optimal sector pattern. In a separate set of repeated visual field data of 303 patients with OAG, the fluctuation of MD, sector values of each sector determined, and total deviation of each test point were calculated and compared. RESULTS: The sector pattern constructed from visual field data of MD > or = -10 dB summarized the visual field performance most effectively. The fluctuation of the sector value of each sector was roughly 1.5 times smaller than the total deviation of each test point. CONCLUSION: The sector pattern determined may be useful in analyses of the visual field data of patients with glaucoma.

Glaucoma, Open-Angle↗

The DEFECTIVE IN ANTHER DEHISCIENCE gene encodes a novel phospholipase A1 catalyzing the initial step of jasmonic acid biosynthesis, which synchronizes pollen maturation, anther dehiscence, and flower opening in Arabidopsis.

The Arabidopsis mutant defective in anther dehiscence1 (dad1) shows defects in anther dehiscence, pollen maturation, and flower opening. The defects were rescued by the exogenous application of jasmonic acid (JA) or linolenic acid, which is consistent with the reduced accumulation of JA in the dad1 flower buds. We identified the DAD1 gene by T-DNA tagging, which is characteristic to a putative N-terminal transit peptide and a conserved motif found in lipase active sites. DAD1 protein expressed in Escherichia coli hydrolyzed phospholipids in an sn-1-specific manner, and DAD1-green fluorescent protein fusion protein expressed in leaf epidermal cells localized predominantly in chloroplasts. These results indicate that the DAD1 protein is a chloroplastic phospholipase A1 that catalyzes the initial step of JA biosynthesis. DAD1 promoter::beta-glucuronidase analysis revealed that the expression of DAD1 is restricted in the stamen filaments. A model is presented in which JA synthesized in the filaments regulates the water transport in stamens and petals.

Amino Acid Sequence↗

[Acute subdural abscess due to mixed infection of Eikenella corrodens and Streptococcus constellatus].

Eikenella corrodens is a gram-negative, facultative anaerobic rod that frequently exists as part of normal human flora in the upper respiratory tract and gastrointestinal tract. Recently, E. corrodens is reported as a rare causative agent of empyematic lesion. We report a case of 10-year-old girl with acute subdural abscess. She developed a high grade fever, swelling of the left periorbital area, right sided partial seizure and hemiplegia. Brain CT and MRI showed left parietal subdural abscess. Because intravenous antibiotic therapy was not effective enough and her neurological symptoms progressed, surgical drainage was performed in order to decompress the brain and to determine the causative agents. Through careful bacterial cultures, E. corrodens and Streptococcus constellatus were detected from the subdural abscess. After the drainage operation and a three week course of appropriate chemotherapy, the abscess completely disappeared and no sequela remained.

Acute Disease↗

Pathogenesis of the gradually elongated nerve.

The rabbits' sciatic nerves were lengthened by 30 mm in increments of 2.0 mm/day (2-mm group) and 4.0 mm/day (4-mm group). In the 2-mm group, the phosphorylated neurofilament (p-NF) immunoreactivity of axons was similar to that of the control group. However, in the 4-mm group, number of p-NF positive axons decreased. The number of p-NF positive cells at the seventh lumbar dorsal root ganglion cells of the 4-mm group was significantly larger than that of the control group. Abnormal p-NF immunoreactivity in the 4-mm group suggested an impairment of the axonal flow. Leakage of Evans blue-albumin into the endoneurial space, which meant destruction of the blood-nerve barrier function, was clearly evident in the 4-mm group, but minor in the 2-mm group. A speed of 2.0 mm/day, therefore, appears to be critical for safe nerve elongation in this model.

Animals↗

Relationship between insulin resistance and uremic toxins in the gastrointestinal tract.

The relationship between insulin resistance and local uremic toxins was examined using an oral adsorbent. Fourteen rats demonstrating a diabetic state underwent two-thirds, nephrectomy and were divided into two groups. The control group was fed standard rat chow, and the test group was fed standard rat chow containing 5% AST-120. The target level of blood glucose was achieved by controlling the dosage of exogenous insulin. All rats were sacrificed at week 6. Body weight, blood glucose level, and renal function at week 6 were not significantly different between both groups. However, the mean blood glucose level and the mean dose of exogenous insulin in the AST-120-fed group were significantly reduced as compared with the control group. The results of the present study indicate that administration of an oral adsorbent in diabetic nephropathy decreases the doses of exogenous insulin and improves insulin resistance, and that uremic toxins which exist in the gastrointestinal tract play important roles.

Adsorption↗

Analysis of pathological tremors using the autoregression model.

The usefulness of analysis of acceleration data using an autoregression model (AR) for differential diagnosis of Parkinson's disease and other diseases with tremors was investigated. The order of the AR model used in this study was 7, in accordance with Akaike's final prediction error criterion. The subjects included 19 patients with Parkinson's disease; 21 patients with essential tremor, which mainly appears in old people, as well as Parkinson's disease; and 13 healthy old people as a control group. The results of analysis of acceleration data showed that the first prediction coefficient, just as the main tremor frequency, was a useful parameter for differentiating patients in the Parkinson's disease patient group and essential tremor patient group. The seventh prediction coefficient was found to be a useful parameter for distinguishing pathological tremors observed in Parkinson's disease and essential tremor disease from physiological tremors observed in healthy people. Although the usefulness of other prediction coefficients for differential diagnosis of Parkinson's disease and other diseases with tremors has not yet been clarified, the results of this study showed that information obtained from AR model parameters in addition to information on main tremor frequency is useful for the diagnosis of Parkinson's disease.

Acceleration↗

Exercise improved accumulation of visceral fat and simultaneously impaired endothelium-dependent relaxation in old rats.

Exercise decreases plasma total cholesterol and triglycerides, and simultaneously, increases high density lipoprotein (HDL) cholesterol. Furthermore, it has been reported that exercise improves insulin resistance. As a result, exercise is believed to aid in preventing atherosclerosis. However, we do not know whether exercise protects against the development of atherosclerosis in the elderly. The aim of this study was to ascertain whether exercise prevented atherosclerosis in aorta of old rats. Exercise for three months did not affect plasma lipid levels but decreased accumulation of visceral fat and body weight without the reduction of food intake in two year old rats. Exercise also decreased triglycerides in liver and gastrocnemius white muscle. Exercise resulted in an elevation of plasma lipid peroxide (LPO) levels without affecting superoxide dismutase (SOD). Exercise impaired the endothelium-dependent relaxation of the thoracic aorta caused by acetylcholine in old rats. In summary, the results of our study indicate that exercise induces the reduction of visceral fat, body weight and triglyceride contents in tissues in old rats. These results seems to show that exercise improves insulin resistance. However, exercise simultaneously may cause impaired endothelium-dependent relaxation by elevation of LPO in old rats.

Adipose Tissue↗

Molecular analysis of defect healing in rat diaphyseal bone.

Spatial expression of messenger ribonucleic acid (mRNA) for osteoblastic marker in drill hole defect healing of adult male rats was analyzed by in situ hybridization. The defect was filled with hematoma 3 days after surgery, expressing Type I collagen mRNA. Hematoma was replaced with fibrous tissue on day 7, and then with new trabecular bone on day 10, originated from the intra-medullary space, respectively. mRNA for Type I collagen, parathyroid hormone 1 receptor (PTHIR), and alkaline phosphatase (ALP) were expressed in the same cell population of fibrous tissue adjacent to newly-formed trabecular bone, and in osteoblasts lining the newly-formed trabecular bone. Hematopoietic marrow with osteoclasts subsequently invaded the region, also from the intra-medullary space, replacing all the new trabecular bone by day 21, except for a thin sub-periosteal layer. mRNA for Type I collagen, PTH1R and ALP was expressed on the periosteal surface of thin layer. Although cartilage formation was not histologically visible, mRNA for Type II collagen was weakly detected in the majority of osteoblasts lining the newly-formed trabecular bone.

Alkaline Phosphatase↗