Search PubMed⌕ Search

Biomedical subjects

N Hotta

Publications and source records attributed to N Hotta.

At least 55 records · Page 3Linked to original sources
PubMed2000

Molecular cloning and partial characterization of rat procarboxypeptidase R and carboxypeptidase N.

Carboxypeptidase R (EC 3.4.17.20) (CPR) and carboxypeptidase N (EC 3.4.17.3) (CPN) cleave carboxy-terminal arginine or lysine residues from biologically active peptides such as kinins or anaphylatoxins in the circulation thereby regulating their activities. Although CPN is present in a stable active form in plasma, CPR is generated from proCPR, a plasma zymogen, by proteolytic enzymes such as thrombin, thrombin-thrombomodulin complex and plasmin. We have isolated rat proCPR and CPN cDNA clones which can induce enzymatic activities in culture supernatants of the transfected cells. mRNA of proCPR was detected only in rat liver by Northern hybridization and showed hepatocyte-specific expression. Expression of proCPR mRNA was enhanced following LPS injection, indicating that proCPR production is increased under inflammatory conditions.

Animals↗
PubMed2000

Physiological responses and RPE during underwater treadmill walking in women of middle and advanced age.

The purpose of this study was to examine the physiological responses and RPE during water walking using the Flowmill, which has a treadmill at the base of a water flume, in order to obtain basic data for prescribing water walking for people of middle and advanced age. Twenty healthy female volunteers with an age of 59.1 +/- 5.2 years took part in this study. They belonged to the same swimming club and regularly swam and exercised in water. Walking in water took place in the Flowmill. Subjects completed four consecutive bouts of 4 min duration at progressively increasing speeds (20, 30, 40 and 50 m/min) with 1 min rest between each bout. In addition, water velocity was adjusted to the walking speed of each bout. Subjects were instructed to swing both arms in order to maintain their balance during walking in water. The water depth was to the level of the xiphoid process and the water temperature was 30.31 +/- 0.08 degrees C. Both heart rate (HR) and oxygen uptake (VO2) increased exponentially as walking speed increased. HR was 125 +/- 15 bpm, and VO2 was 18.10 +/- 2.72 ml/kg.min-1 during walking in water at 50 m/min, which was the highest speed. The exercise intensity at this speed was equivalent to 5.2 +/- 0.8 Mets. The relationship between HR and VO2 during walking in water showed a highly significant linear relationship in each subject. There was also a highly significant linear relationship in the mean HR and VO2 of all subjects. Blood lactate concentration (LA) measured at rest and immediately after each bout was 1.1 +/- 0.4 mmol/l at rest, 1.0 +/- 0.2 mmol/l at 20 m/min, 1.0 +/- 0.3 mmol/l at 30 m/min, 1.1 +/- 0.2 mmol/l at 40 m/min, and 2.4 +/- 0.7 mmol/l at 50 m/min. LA at 50 m/min was significantly higher than at rest and at the other speeds. The relationship between HR and RPE during walking in water showed a highly significant linear relationship. The relationship between walking speed and energy expenditure calculated from VO2 and the respiratory exchange ratio (R) showed a high significant exponential relationship. These results suggested that HR and RPE can be effective indices for exercise prescription during Flowmill walking as with land walking.

Aged↗
PubMed2000

Epalrestat, an aldose reductase ihibitor, reduces the levels of Nepsilon-(carboxymethyl)lysine protein adducts and their precursors in erythrocytes from diabetic patients.

OBJECTIVE: To clarify the role of the polyol pathway in the intracellular formation of advanced glycation end products in human tissues, we examined the effects of epalrestat, an aldose reductase inhibitor, on the level of Nepsilon-(carboxymethyl)lysine (CML) along with 3-deoxyglucosone (3-DG) and triosephosphates in erythrocytes from diabetic patients. Plasma thiobarbituric acid-reactive substances (TBARS) were also determined as indicators of oxidative stress. RESEARCH DESIGN AND METHODS: Blood samples were collected from 12 nondiabetic volunteers, 38 untreated type 2 diabetic patients, and 16 type 2 diabetic patients who had been treated with 150 mg epalrestat/day. Blood samples were also collected from 14 of the untreated type 2 diabetic patients before and after the administration of epalrestat for 2 months. The amount of erythrocyte CML was determined by a competitive enzyme-linked immunosorbent assay, and 3-DG was measured by high-performance liquid chromatography RESULTS: In diabetic patients not treated with epalrestat, the erythrocyte CML level was significantly elevated above levels seen in nondiabetic individuals (49.9 +/- 5.0 vs. 31.0 +/- 5.2 U/g protein, P < 0.05) and was significantly lower in patients receiving epalrestat (33.1 +/- 3.8 U/g protein, P < 0.05). Similar results were observed with 3-DG. The treatment of patients with epalrestat for 2 months significantly lowered the level of erythrocyte CML (46.2 +/- 5.6 at baseline vs. 34.4 +/- 5.0 U/g protein, P < 0.01) along with erythrocyte 3-DG (P < 0.05), triosephosphates (P < 0.05), fructose (P < 0.05), sorbitol (P < 0.05), and plasma TBARS (P < 0.05) without changes in plasma glucose and HbA(1c) levels. A positive correlation was evident between the erythrocyte CML and sorbitol (r = 0.49, P < 0.01) or fructose (r = 0.40, P < 0.05) levels in diabetic patients. CONCLUSIONS: The results indicate that epalrestat administration lowers CML and associated variables and that polyol metabolites are correlated with CML in the erythrocytes of diabetic patients. The observed results suggest that aldose reductase activity may play a substantial role in the intracellular formation of CML in the mediation of reactive intermediate metabolites and oxidative stress.

Aldehyde Reductase↗
PubMed1999

Observation of Multi-TeV Gamma Rays from the Crab Nebula using the Tibet Air Shower Array.

The Tibet experiment, operating at Yangbajing (4300 m above sea level), is the lowest energy air shower array, and the new high-density array constructed in 1996 is sensitive to gamma-ray air showers at energies as low as 3 TeV. With this new array, the Crab Nebula was observed in multi-TeV gamma-rays and a signal was detected at the 5.5 sigma level. We also obtained the energy spectrum of gamma-rays in the energy region above 3 TeV which partially overlaps those observed with imaging atmospheric Cerenkov telescopes. The Crab spectrum observed in this energy region can be represented by the power-law fit dJ&parl0;E&parr0;&solm0;dE=&parl0;4.61+/-0.90&parr0;x10-12&parl0;E&solm0;3 TeV&parr0;-2.62+/-0.17 cm-2 s-1 TeV-1. This is the first observation of gamma-ray signals from point sources with a conventional air shower array using scintillation detectors.

Journal Article↗
PubMed1999

An aldose reductase inhibitor prevents the glucose-induced increase in PDGF-beta receptor in cultured rat aortic smooth muscle cells.

To examine the role of platelet-derived growth factor (PDGF) and the polyol pathway in the growth activity of smooth muscle cells (SMCs), [(3)H]-thymidine incorporation, [(125)I]-PDGF-BB binding and expression of PDGF-beta receptor protein were measured in rat aortic SMCs cultured with 5.5 or 20 mM glucose with or without anti-PDGF antibody or an aldose reductase inhibitor, epalrestat. SMCs cultured with 20 mM glucose demonstrated an accelerated thymidine incorporation compared with SMCs cultured with 5.5 mM glucose, which was prevented by anti-PDGF antibody. This acceleration of growth activity by 20 mM glucose was accompanied by an increase in PDGF-BB binding, which was due to the increased number of PDGF-beta receptors and the overexpression of PDGF-beta receptor protein. Epalrestat prevented all these abnormalities. These observations suggest that polyol pathway hyperactivity plays an important role in the proliferation of SMCs which may be mediated through the accelerated expression of PDGF-beta receptor protein.

Aldehyde Reductase↗
PubMed1999

An aldose redutase inhibitor prevents the intimal thickening in coronary arteries of galactose-fed beagle dogs.

AIMS/HYPOTHESIS: Although increased polyol pathway activity has been implicated in the pathogenesis of diabetic microangiopathy, the relation with diabetic macroangiopathy remains unclear. Galactose feeding is known to stimulate the polyol pathway and to develop abnormalities similar to those in diabetic microangiopathy. Our study was conducted to investigate whether an activation of polyol pathway by long-term treatment with galactose produced morphological changes in coronary arteries of dogs and the effect of an aldose reductase inhibitor, epalrestat, was also studied. METHODS: Dogs received either normal chow or chow containing 30% galactose with or without epalrestat given orally (20 or 50 mg x kg(-1)). After 44 months, morphometric analyses of coronary arteries were carried out and the galactitol contents in aortas were measured. RESULTS: The ratio of areas of the intimal layer to those of the medial layer, an indicator of intimal thickening, was statistically significantly increased in galactose-fed dogs compared with control dogs. Galactose-fed dogs had a remarkable accumulation of galactitol in their aortas. These morphological and biochemical deficits were reduced by treatment with epalrestat. CONCLUSION/INTERPRETATION: This report morphologically shows diabetes-like macrovascular abnormalities in galactosaemic animals, suggesting that polyol pathway hyperactivity is closely related to the development of diabetic macroangiopathy, which could be prevented by aldose reductase inhibition.

Aldehyde Reductase↗
PubMed1999

Effect of vitamin E and allylamine on the proliferation of cultured aortic smooth muscle cells from streptozotocin-induced diabetic rats.

To investigate the effect of vitamin E on the proliferation activity of vascular smooth muscle cells (SMCs) in diabetes mellitus, [3H]-thymidine incorporation was measured in cultured SMCs isolated from normal and streptozotocin-induced diabetic rats treated with or without vitamin E and/or allylamine. Untreated diabetic rats demonstrated significantly elevated concentrations of serum total cholesterol, triglycerides and malondialdehyde (MDA). Allylamine caused a further increase in serum MDA. Treatment with vitamin E decreased the serum concentrations of triglycerides and MDA in both allylamine-treated and -untreated diabetic rats. [3H]-Thymidine incorporation in cultured SMCs from diabetic rats was significantly increased compared with that from normal rats. SMCs from allylamine-treated diabetic rats showed an enhanced increase in thymidine incorporation compared with that from untreated diabetic rats. The increase in thymidine incorporation in SMCs from untreated and allylamine-treated diabetic rats was significantly reduced by the treatment with vitamin E. These observations suggest that vitamin E has a preventive effect on the proliferation of vascular SMCs in diabetes, and that this effect may be mediated through an enhancement of free radical scavenging.

Allylamine↗
PubMed1999

Risk factors for IgA nephropathy: a case-control study in Japan.

To disclose the risk factors for immunoglobulin A nephropathy (IgAN), we conducted a case-control study in the Tokai area of central Japan. The subjects were 94 patients, aged 20 years or older at diagnosis, who had histologically confirmed IgAN. Two sex-, age-, and residence-matched controls were randomly selected for each case from the general population. Information on medical history and lifestyle was collected using a self-administered questionnaire. The strength of association between IgAN and a potential risk factor was assessed by calculating an odds ratio. A family history of chronic nephritis, susceptibility to the common cold, preference for salty foods, frequent consumption of raw eggs, and a high intake of carbohydrates, including rice, were significantly associated with an increased risk for IgAN. Alcohol consumption, use of antioxidant vitamin supplements, and a high intake of protein, fat, monounsaturated fatty acids, and all/n-3 polyunsaturated fatty acids were somewhat protective against IgAN. Episodes of tonsillitis and exposure to organic solvents were found not to be associated with the risk in the present study. Our findings may provide some clues to the cause of IgAN.

Adult↗
PubMed1999

Effect of aldose reductase inhibitors on glucose-induced changes in sorbitol and myo-inositol metabolism in human neutrophils.

AIM: To investigate the influence of glucose and the efficacy of two different aldose reductase (AR) inhibitors, epalrestat and SNK-860, on the polyol pathway and myo-inositol metabolism in human neutrophils. METHODS: We incubated neutrophils with various concentrations of glucose and AR inhibitors. The neutrophils from healthy volunteers were incubated in the media containing 5-40 mmol/l glucose with or without an AR inhibitor. The sorbitol and myo-inositol contents, and myo-inositol uptake were measured by high performance liquid chromatography and radio isotope technique with 2-[3H]-myo-inositol. RESULTS: After 2 h incubation, the sorbitol content increased with rising extracellular glucose concentrations, while the myo-inositol content decreased. Both AR inhibitors reduced the sorbitol content in neutrophils exposed to 40 mmol/l glucose medium. A 70% fall in the myo-inositol content in neutrophils exposed to 40mmol/glucose medium was attenuated approximately 40% by the addition of AR inhibitors. myo-Inositol uptake into neutrophils was inhibited by high glucose. AR inhibitors significantly ameliorated the decrease in myo-inositol uptake, but did not completely normalize it. CONCLUSIONS: Our present in vitro studies showed that the glucose-induced metabolic alterations in human neutrophils were similar to those in tissues prone to diabetic complications, and that AR inhibitors effectively corrected glucose-induced imbalances of the polyol pathway and myo-inositol uptake in neutrophils. In addition, our study suggests that glucose-induced metabolic alterations may result in the neutrophil dysfunction and that an AR inhibitor may be capable ameliorating it.

Adult↗
PubMed1999

Characterization of a newly found stretch-activated KCa,ATP channel in cultured chick ventricular myocytes.

With the use of the patch-clamp technique, five kinds of stretch-activated (SA) ion channels were identified on the basis of their single-channel conductances and ion selectivities in cultured chick ventricular myocytes. Because a high-conductance K+-selective channel predominated among these channels, we concentrated on characterizing its properties mostly using excised inside-out patches. With 145 mM KCl solution in the pipette and the bath, the channel had a conductance of 199.8 +/- 8.2 pS (n = 22). The ion selectivities among K+, Na+, Ca2+, and Cl- as estimated from their permeability ratios were PNa/PK = 0.03, PCa/PK = 0.025, and PCl/PK = 0.026. The probability of the channel being open (Po) increased with the Ca2+ concentration in the bath ([Ca2+]b; dissociation constant Kd = 0.51 microM at +30 mV) and membrane potential (voltage at half-maximal Po = 39.4 mV at 0.35 microM [Ca2+]b). The channel was blocked by gadolinium, tetraethylammonium, and charybdotoxin from the extracellular surface and, consequently, was identified as a Ca2+-activated K+ (KCa) channel type. The channel was also reversibly activated by ATP applied to the intracellular surface (Kd = 0.74 mM at 0.10 microM [Ca2+]b at +30 mV). From these data taken together, we concluded that the channel is a new type of KCa channel that could be designated as an "SA KCa,ATP channel." To our knowledge, this is the first report of KCa channel in heart cells.

Adenine Nucleotides↗
PubMed1999

Central nervous system-mediated hyperglycemic effects of NIK-247, a cholinesterase inhibitor, and MKC-231, a choline uptake enhancer, in rats.

We investigated the effects of intracerebroventricular administration of NIK-247 (9-amino-2,3,5,6,7,8-hexahydro-1H-cyclo-penta(b)-quinoline monohydrate hydrochloride; a cholinesterase inhibitor) or MKC-231 (2-(2-oxypyrrolidin-1-yl)-N-(2,3-dimethyl-5,6,7,8-tetrahydrofur o[2,3-b]quinolin-4-yl) acetoamide; a choline uptake enhancer) on plasma glucose level in comparison with that of neostigmine administration in rats. The extents of NIK-247- and MKC-231-induced hyperglycemia were considerably less than that by neostigmine, suggesting that the potencies of the drugs to produce the peripheral hyperglycemia may be pharmacologically negligible.

Aminoquinolines↗
PubMed1999

A protein kinase C-beta-selective inhibitor ameliorates neural dysfunction in streptozotocin-induced diabetic rats.

Increased protein kinase C (PKC) activity has been implicated in the pathogenesis of diabetic retinopathy and nephropathy. However, the role of PKC in diabetic neuropathy remains unclear. The present study was conducted to compare the effect of PKC inhibition by a PKC-beta-selective inhibitor, LY333531 (LY), on diabetic nerve dysfunction with that of an aldose reductase inhibitor, NZ-314 (NZ). Streptozotocin-induced diabetic rats were treated with or without LY and/or NZ for 4 weeks, and motor nerve conduction velocity (MNCV), coefficient of variation of R-R interval (CVR-R), sciatic nerve blood flow (SNBF), peak latencies of oscillatory potentials on electroretinogram, PKC activities in membranous and cytosolic fractions of sciatic nerves, and polyol contents in the tail nerves were measured. Untreated diabetic rats demonstrated delayed MNCV, decreased CVR-R, reduced SNBF, and prolonged peak latencies of oscillatory potentials. Treatment with LY as well as NZ prevented all these deficits in diabetic rats. There were no significant differences in PKC activities in membranous or cytosolic fractions of sciatic nerves between normal and diabetic rats. Treatment with neither LY nor NZ altered PKC activities. Nerve myo-inositol depletion in diabetic rats was ameliorated not only by NZ, but also by LY. These observations suggest that inhibition of PKC-beta by LY may have a beneficial effect in preventing the development of diabetic nerve dysfunction, and that this effect may be mediated through its action on the endoneurial micro-vasculature.

Aldehyde Reductase↗
PubMed1999

Hyaluronan activates mitogen-activated protein kinase via Ras-signaling pathway.

Hyaluronan (HA) triggers a wide variety of cellular functions, yet its signaling pathway remains largely unclear. We found that HA-treatment of 3Y1 cells activated tyrosine phosphorylation of cellular proteins and mitogen-activated protein (MAP) kinase in a time- and dose-dependent manner, and, subsequently, stimulated cell growth. This HA-activity was resistant to boiling at 100 degrees C but completely abolished by treatment with hyaluronidase, suggesting that HA itself, but not any HA-associated proteins, has the activity. In addition, we found that HA-dependent activation of MAP kinase was strongly suppressed by the expression of dominant negative ras (S17N ras). These results suggest that Ras-MAP kinase pathway is activated by HA and may play an important role in HA-dependent signaling.

Adjuvants, Immunologic↗
PubMed1999

[Aldose reductase].

Explore the source record for details and available documents.

Aldehyde Reductase↗
PubMed1998

Effects of propionyl-L-carnitine on cardiac dysfunction in streptozotocin-diabetic rats.

The effects of orally administered propionyl-L-carnitine on cardiac dysfunction in rats with streptozotocin-induced diabetes were investigated. Wistar male rats were divided into four groups: untreated normal, propionyl-L-carnitine (daily for 4 weeks with 3 g/kg orally) -treated normal, untreated diabetic, propionyl-L-carnitine-treated diabetic. Four weeks after streptozotocin administration, plasma lipid levels were increased and myocardial carnitine content was decreased in untreated diabetic rats. These changes were significantly reversed by the propionyl-L-carnitine treatment. Assessment of cardiac function with isolated perfused working hearts revealed a depression of left ventricular developed pressure as well as both maximum positive and negative dP/dt in untreated diabetic as compared with that in normal hearts. Cardiac function at the higher left atrial filling pressures in the propionyl-L-carnitine-treated diabetic rats was improved significantly compared to that in untreated hearts. The data thus suggest that oral administration of propionyl-L-carnitine can reduce abnormalities of cardiac function, correlated with a significant increase in myocardial carnitine content and improved lipid metabolism in terms of lowered plasma lipids.

Administration, Oral↗
PubMed1998

Demonstration of a Ca2+/calmodulin dependent protein kinase cascade in the hog heart.

Members of the Ca2+/calmodulin dependent protein kinase (CaMK) family and a CaMK cascade have been identified and well characterized in the brain, but little is known about their equivalents in the heart. Thus only CaMKII and its function have been reported so far. Therefore, we purified and characterized CaMKI and CaMK kinase (CaMKK) as an associated activator from the hog heart for the first time. The heart CaMKI was revealed to be the alpha isoform of brain CaMKI with a molecular weight of 41 kDa to phosphorylate cardiac phospholamban peptide, and to exhibit autophosphorylation requiring CaMKK. Heart CaMKK was found as a 67 kDa band and proved to be a different kinase from that in brain. These data indicate the existence of a heart specific CaMK cascade, consisting of CaMKI and CaMKK, along with CaMKII, which should be taken into account in any consideration of Ca2+ signal transduction.

Amino Acid Sequence↗