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Biomedical subjects

N Sakamoto

Publications and source records attributed to N Sakamoto.

At least 127 records · Page 7Linked to original sources
PubMed1997

A two-dimensional compartment model for the reaction-diffusion system of acetylcholine in the synaptic cleft at the neuromuscular junction.

A minimal compartment model of the reaction-diffusion system (RD system) of a neurotransmitter in a two-dimensional space of axis-symmetrical disc is proposed to represent the chemical transmission process of a quantum of acetylcholine (ACh) in the synaptic cleft at the neuromuscular junction. The behavior of the RD system for ACh is expressed by a two-dimensional diffusion equation with nonlinear reaction terms due to the rate processes for ACh receptor and acetylcholinesterase. The simulation analysis of the RD system reveals that the radial diffusion process of ACh has more distinctive effects on spontaneous generation of the miniature endplate current (MEPC) than the transverse process. The anisotropic diffusion is effective in the RD system since the diffusion coefficient of ACh in the radial direction is evaluated to be about 1.0 x 10(-6) cm2 sec-1 for appropriate characterization of the MEPC, on which the diffusion coefficient in the transverse direction larger than 2.0 x 10(-6) cm2 sec-1 has virtually no effects. The compartment model is thus appropriately constructed to comprise three elements on the transverse coordinate and ten elements on the radial coordinate in the disc with 500 nm of radius and 50 nm of height.

Acetylcholine↗
PubMed1997

Prion protein is necessary for latent learning and long-term memory retention.

1. The cellular prion protein, designated PrPc, is a key molecule in the prion diseases but its physiological function remains unknown. To elucidate whether PrPc plays some role in the central nervous system, we established a line of mice in which the PrP gene had been disrupted and subsequently conducted long-term observations. 2. Performance in latent learning and passive avoidance was evaluated using water-finding and step-through tests, respectively. 3. PrP-/- mice showed impaired performance in the water-finding test, indicating a disturbance in latent learning, at 23 weeks of age. In the step-through test, although the PrP-/- mice showed normal learning ability and short-term memory retention, they evidenced a significant disturbance in long-term memory retention. 4. These results indicate that PrPc is needed for certain types of learning and memory and that the loss of function of this protein may contribute to the pathogenesis of prion diseases.

Animals↗
PubMed1997

Dual effects of endothelins on the muscarinic K+ current in guinea pig atrial cells.

Effects of endothelins (ETs) on the acetylcholine receptor-operated K+ current (I(KACh)) were examined in isolated guinea pig atrial cells using patch-clamp techniques. ET-1 or ET-3 produced a transient activation of I(KACh) in atrial cells held at -40 mV. When I(KACh) was preactivated by 1 microM carbachol, however, both ETs produced a transient potentiation followed by a sustained inhibition of the current. When I(KACh) was maximally activated by 10 microM carbachol or 100 microM adenosine, these ETs produced only a sustained inhibition of the I(KACh). Their inhibitory effects on the preactivated I(KACh) were concentration dependent, and the half-maximal effective concentrations were 314 pM for ET-1 and 1.13 nM for ET-3. The inhibitory effect of ET-1 was antagonized by BQ-485, a specific ET(A) receptor antagonist, but not by BQ-788, a specific ET(B) receptor antagonist, indicating that the ET-1 effect is mediated by ET(A) receptors. On the other hand, the inhibitory effect of ET-3 was antagonized by BQ-788 and more effectively by BQ-485, suggesting the involvement of "atypical" ET receptors. Both ETs partly reversed the carbachol-induced shortening of the action potential recorded in the current-clamp mode. Inhibitory effects of ET-1 and ET-3 on the preactivated I(KACh) may contribute to the positive inotropic and chronotropic effects of ETs in atrial tissues.

Acetylcholine↗
PubMed1997

The mechanism of anticoagulant activity of a novel heparinoid sulfated glucoside-bearing polymer.

In our previous study on glycoside polymer, it was discovered that sulfated poly(glucosyloxyethyl methacrylate) [poly(GEMA)-sulfate], which bears sulfated D-(+)-glucose, exhibited anticoagulant activity. The anticoagulant activity of poly(GEMA)-sulfate in solution was prolonged by increasing the dose or degree of sulfation of the polymer. In this study, to recognize the mechanism of anticoagulant activity of poly(GEMA)-sulfate, we estimated the binding capacity of antithrombin III to thrombin and some in vitro clotting tests in the presence of poly(GEMA)-sulfate. These results revealed that poly(GEMA)-sulfate had an anticoagulant mechanism which differed to that of heparin. We concluded that the anticoagulant activity of poly(GEMA)-sulfate is responsible for inhibiting fibrin network formation by the insoluble ion complex between fibrinogen and poly(GEMA)-sulfate.

Anticoagulants↗
PubMed1997

[An anaphylactic shock case after hepatic arterial infusion of zinostatin stimalamer suspension improved by anti-histaminics].

A 47-year-old man with hepatocellular carcinoma (HCC) at anterior and medical segment in the liver was treated with hepatic arterial infusion of Zinostatin Stimalamer-lipiodol suspension (SMANCS). After the 2nd infusion of SMANCS, the accumulation of lipiodol in the tumor was not good (Grade II), so additional administration was undertaken at five-weeks intervals. His systolic blood pressure immediately decreased from 120 to 60 mmHg, and he had numbness of hands, shaking chills, sweating, chest pain and numerous urticaria-like red exanthema. In spite of treatment by anti-shock agents such as steroid and catecholamines, these symptoms did not disappear, but antihistaminics greatly improved them without any serious side effects. Because of the remarkable effects of the antihistaminics and possibility of antibody production (IgE) after repeated infusions of high molecular SMANCS, this patient may have suffered anaphylactic shock caused by massive histamine release from mast cells.

Anaphylaxis↗
PubMed1997

Tumor-specific synergistic therapy of mitomycin C: modulation of bioreductive activation.

The bioreductive activation of mitomycin C (MMC) has been investigated using 10 human cancer cell lines. Except for 2 lines (COLO201 and COLO320DM), the cellular NAD(P)H: quinone oxidoreductase (DTD) activities correlated well with MMC-induced DNA damage and cytotoxicity. In addition, when the DTD activity was inhibited with 50 mM dicoumarol, the MMC activity decreased significantly. On the other hand, no correlation between the NADPH cytochrome P450 reductase (P450) activity and MMC efficacy was observed. We postulate that two electron reduction by DTD may be more important in MMC activation than one electron reduction by P450. The DTD-mediated metabolism was pH-dependent. In a nude mouse experimental model, the pH in the tumor decreased under hyperglycemic conditions due to unique glycolysis. The administration of m-iodobenzyl-guanidine (MIBG) enhanced the decrease in the pH of the tumor without affecting the pH of normal tissue (liver). It also significantly increased the antitumor activity of MMC. However, this biochemical modulation had no effect in the COLO201 and COLO320DM cells. Other mechanisms may be involved in the regulation of MMC activity in these cells. In conclusion, DTD may be an important target of MMC. Biochemical modulation using MIBG and glucose may selectively enhance the activity of MMC within cancer cells.

3-Iodobenzylguanidine↗
PubMed1997

[Regional cerebral hypoperfusion reduces the effect of rectal midazolam in children with Moyamoya disease].

To investigate the effect of regional cerebral blood flow on the effect of midazolam, we evaluated 99mTc-hexamethylpropylene-amine-oxime-single photon emission computed tomography (SPECT) in 37 cases of childhood moyamoya disease. They were divided into two groups according to the findings of SPECT; one group showed hypoperfusion in the bifrontal regions (n = 20), and the other did not (n = 17). Both groups received 1 mg.kg-1 of midazolam transrectally 30 min before the anesthesia induction and level of sedation was measured with six point scales. Significantly lower level of sedation score was recognized in the group that showed hypoperfusion in bifrontal regions (P < 0.05). Our finding may suggest that regional cerebral hypoperfusion may modify the sedative effect of midazolam in children with moyamoya disease.

Administration, Rectal↗
PubMed1997

Relationship between mortality rate of stomach cancer and cerebrovascular disease and concentrations of magnesium and calcium in well water in Hyogo prefecture.

The concentration of Mg, Ca and total hardness of well and tap water were examined in 98 towns and cities in Hyogo prefecture. The annual mortality rates of stomach cancer and CVD in these areas during 1975-1979 were analyzed by the concentration of Mg and Ca in well water. The mortality rate of stomach cancer was correlated significantly positively to Mg2+/Ca2+ ratio of well water, and a similar tendency was shown in tap water. A covariance analysis indicated Mg2+ to be correlated significantly to the mortality rate of stomach cancer. Thus, it is suggested that the relatively high concentration of Mg2+ compared to Ca2+ in drinking water might be one of the causes of stomach cancer in Japanese. But the concentration of Ca2+ was correlated significantly negatively to the mortality rate of CVD.

Calcium↗
PubMed1996

Intracellular cleavage of hepatitis C virus RNA and inhibition of viral protein translation by hammerhead ribozymes.

To determine the effects of hammerhead ribozymes against hepatitis C virus (HCV) RNA on viral protein translation, a luciferase reporter gene vector, pCMV/T7-NCRCdelta-luc, was constructed containing the 5'-noncoding region (5'-NCR) and part of the core region of HCV. Four ribozymes, Rz1-Rz4, were designed to cleave at nucleotide positions 136-160, 313-337, 496-520, and 373-388, respectively. Each ribozyme cleaved the target RNA at expected positions under cell-free conditions. Rz2 and Rz4 significantly suppressed translation of NCRCdelta-luc RNA by 71 and 49%, respectively. Translation of control luciferase mRNA lacking viral elements was not affected by the ribozymes. Furthermore, when NCRCdelta-luc RNA and ribozymes were cotransfected into cells, Rz2 and Rz4 significantly suppressed expression by 73 and 56%, respectively. In contrast, cleavage-deficient ribozymes with a point mutation in the hammerhead domain had no significant effect. To determine the effects of endogenously produced ribozymes, eukaryotic expression vectors for Rz2 and Rz4 were constructed. Cotransfection of the vectors with CMV/T7-NCRCdelta-luc showed suppression of luciferase activities to 50 and 61%, respectively. Moreover, transfection of pCMV/T7-NCRCdelta-luc into stable Rz2 and Rz4 producer cells also showed substantial inhibition of luciferase activity. Ribozymes directed against the HCV genome can substantially and specifically inhibit viral gene expression under intracellular conditions.

Cells, Cultured↗
PubMed1996

Nerve function and blood flow in Otsuka Long-Evans Tokushima Fatty rats with sucrose feeding: effect of an anticoagulant.

To investigate the pathogenesis of diabetic neuropathy in non-insulin-dependent diabetes mellitus, Otsuka Long-Evans Tokushima Fatty rats, an animal model of non-insulin-dependent diabetes mellitus, and non-diabetic Long-Evans Tokushima Otsuka rats were fed with or without sucrose and/or cilostazol, an anticoagulant, for 8 weeks. Sucrose-fed diabetic rats showed a delayed motor nerve conduction velocity, decreased R-R interval variability of electrocardiogram, reduced sciatic nerve blood flow, increased platelet aggregability and a decreased erythrocyte 2,3-diphosphoglycerate concentration compared with non-sucrose-fed diabetic rats and non-diabetic rats. These abnormalities were significantly prevented by treatment with cilostazol without changes in the nerve tissue levels of polyols. These findings indicate that sucrose-fed Otsuka Long-Evans Tokushima Fatty rats may be a useful animal model of neuropathy in non-insulin-dependent diabetes mellitus, and that cilostazol may prevent the development of diabetic neuropathy by modifying vascular factors.

2,3-Diphosphoglycerate↗
PubMed1996

Effect of propionyl-L-carnitine on oscillatory potentials in electroretinogram in streptozotocin-diabetic rats.

The effect of propionyl-L-carnitine, an analogue of L-carnitine, and insulin on the oscillatory potentials of the electroretinogram was determined in rats with streptozotocin-induced diabetes. Propionyl-L-carnitine was administered at a daily dose of 0.5 g/kg by gavage for 4 weeks, while other rats were treated with subcutaneous injections of insulin (8-10 U/day). Both treatments shortened the peak latencies of the oscillatory potentials in the electroretinogram, which were significantly prolonged in untreated diabetic rats (O1, O2 and O3, and sigma (O1 + O2 + O3)) (P < 0.0001 vs. untreated normal rats). A significant decrease in the erythrocyte free carnitine level in diabetic rats was prevented by both treatments. Insulin produced a significant reduction of retinal glucose, sorbitol and fructose levels in diabetic rats, while propionyl-L-carnitine failed to do so. However, both treatments markedly reduced serum lipids levels in the diabetic rats. These findings provide information on the pathogenesis of diabetic retinopathy as well as suggesting the potential therapeutic value of propionyl-L-carnitine for retinopathy.

Analysis of Variance↗
PubMed1996

Dynamic Small-Angle X-ray Scattering System using an Imaging Plate.

A synchrotron-radiation dynamic small-angle X-ray scattering (Synchrotron Radiation-DSAXS) system using an imaging plate has been developed at the Photon Factory, National Laboratory for High Energy Physics, Japan, in collaboration with the Department of Polymer Chemistry, Kyoto University, Japan, for studying the dynamic response of mesoscopic structures in polymers to applied mechanical stimuli. Small-angle X-ray scattering patterns of 100 x 100 mm(2) have been successively recorded on a 400 x 200 mm(2) stage-mounted imaging plate with a minimum time interval of 0.5 s. X-ray data are simultaneously obtained with stress and strain measurements on specimens subjected to a mechanical deformation. The performance of the DSAXS system is demonstrated along with some experimental results concerning the dynamic deformation of a b.c.c. lattice with paracrystalline distortion in a co-polymer having spherical microdomains under a large oscillatory shear deformation.

Journal Article↗
PubMed1996

An impaired carotid sinus distensibility and baroreceptor sensitivity alter autonomic activity in patients with effort angina associated with significant coronary artery disease.

Baroreceptor sensitivity and carotid sinus distensibility were lower in patients with angina associated with significant coronary artery disease than in patients with vasospastic angina. Baroreceptor sensitivity was significantly correlated with carotid sinus distensibility in both groups of patients.

Angina Pectoris↗