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Biomedical subjects

N Nakayama

Publications and source records attributed to N Nakayama.

At least 37 records · Page 2Linked to original sources

Differential properties of the optical-isomers of pranidipine, a 1,4-dihydropyridine calcium channel modulator.

Pranidipine is an optically-active 1,4-dihydropyridine (DHP) voltage-dependent L-type calcium channel inhibitor. Certain enantiomeric pairs display opposite effects, i.e., inhibition and activation of the calcium channel while others exhibit the same qualitative actions. We investigated pranidipine, a new DHP, using a paradigm of vascular smooth muscle reactivity. In isolated rat aorta, depolarized with 80 mM KCl, both isomers of pranidipine caused a right-ward shift of the concentration-contraction curves for extracellular Ca2+. The apparent pA2, values of the S-isomer and R-isomer were 10.03 and 8.36, respectively, providing evidence that the calcium channel blocking action of the S-isomer was 50 times more potent than that of the R-isomer. Antihypertensive actions of these two isomers studied in pentobarbital-anaesthetized spontaneously hypertensive rats, revealed that the S-isomer, at doses of 3-30 microg/kg i.v. decreased blood pressure in a dose-dependent manner, while the R-isomer had no effect on blood pressure at those doses. We conclude that the pair of enantiomers of pranidipine qualitatively display the same Ca2+ channel blocking action and that neither isomer exhibits Bay K 8644-like activation. Pranidipine may be useful in studies on the architecture of the DHP receptor 'pocket'.

Analysis of Variance↗

Skull metastasis of Ewing's sarcoma--three case reports.

Three cases of skull metastasis of Ewing's sarcoma were treated. The metastatic lesion was located at the midline of the skull above the superior sagittal sinus in all cases. Surgery was performed in two patients with solitary skull lesions involving short segments of the superior sagittal sinus without remarkable systemic metastasis, resulting in good outcome. The third patient had extensive, multiple tumors involving the superior sagittal sinus which could not be excised, and died due to intracranial hypertension. The surgical indication for skull metastasis of Ewing's sarcoma depends on the location and length of the involved superior sagittal sinus, and general condition.

Adolescent↗

Clinical application of three-dimensional anisotropy contrast magnetic resonance axonography. Technical note.

The utility of three-dimensional anisotropy contrast (3DAC) magnetic resonance (MR) axonography, a method sensitive to neuronal fibers and their directionality, was investigated in the clinical setting using a 3-tesla MR imaging system based on a General Electric Signa platform. The study focused on healthy volunteers and patients with common structural central nervous system disorders, namely chronic infarction, brainstem cavernous hemangioma, supratentorial meningioma, and astrocytoma. Three orthogonal anisotropic diffusion-weighted images were first obtained. Three primary colors were each assigned to a diffusion-weighted image, respectively, and the images were subsequently combined into a single-color image in full-color spectrum (3DAC MR axonography image). Fiber-tract definition in the cerebral peduncle of the midbrain of healthy volunteers showed intersubject variation, with two general patterns recognized: dispersed (60% of cases) and compact (40% of cases). Pathological alterations in the fiber tracts were readily identified in cases involving wallerian degeneration of the pyramidal tract, as illustrated in the cases of chronic infarction. Displacement of major tracts, such as the medial lemniscus or corticospinal tract, as well as fiber directionality, was also easily recognized in cases of mass lesions. As an imaging method uniquely capable of providing information regarding axonal connectivity, 3DAC MR axonography appears to have promising potential for routine clinical application.

Astrocytoma↗

[The role of discharge coordination nurses in a university hospital--changes in the role with timing of the discharge request].

UNLABELLED: We studied the role of discharge assisting nurses who coordinate discharge planning (DP). The requests for DP were ordered at different periods during the admission. The periods were mainly divided into three phases in which the DP was ordered from the wards, which were type 1: just before discharge, type 2: after the decision to discharge, and type 3: between admission and the decision to discharge. We analyzed 8 cases, DP ordered in the type 3 phase provided the most satisfactory outcome for patients' home lives, since the nurse, other medical staff and patients had sufficient time to prepare and provide the needed services. CONCLUSION: It was clarified that type 3 provided the best outcome of discharge planning.

Hospitals, University↗

Arteriovenous malformation in association with moyamoya disease. Report of two cases.

The authors report two rare cases of arteriovenous malformation (AVM) associated with moyamoya disease. An AVM, supplied by transdural communicating arteries, was located in the right occipital lobe in one patient who presented with ischemia. The second AVM, which was supplied by basal moyamoya vessels, was located in the posterior part of the left frontal lobe in a patient who developed intracerebral hemorrhage that occupied the left basal ganglion. A review of the literature revealed a total of 12 AVMs in 11 patients with moyamoya disease including our cases. All AVMs were cerebral and two were supplied by normal cerebral arteries, whereas six AVMs were supplied by basal moyamoya vessels at the base of the brain and four AVMs were supplied by external carotid arteries through the transdural communicating arteries. Every AVM drained into deep or cortical cerebral veins. These findings suggest that the hyperangiogenic character of moyamoya disease occasionally induces the development of acquired arteriovenous shunts that mimic AVM.

Journal Article↗

Functions of the two glutamate transporters GLAST and GLT-1 in the retina.

In the retina, the glutamate transporter GLAST is expressed in Müller cells, whereas the glutamate transporter GLT-1 is found only in cones and various types of bipolar cells. To investigate the functional role of this differential distribution of glutamate transporters, we have analyzed GLAST and GLT-1 mutant mice. In GLAST-deficient mice, the electroretinogram b-wave and oscillatory potentials are reduced and retinal damage after ischemia is exacerbated, whereas GLT-1-deficient mice show almost normal electroretinograms and mild increased retinal damage after ischemia. These results demonstrate that GLAST is required for normal signal transmission between photoreceptors and bipolar cells and that both GLAST and GLT-1 play a neuroprotective role during ischemia in the retina.

ATP-Binding Cassette Transporters↗

Natural killer and B-lymphoid potential in CD34+ cells derived from embryonic stem cells differentiated in the presence of vascular endothelial growth factor.

Differentiation of totipotent mouse embryonic stem (ES) cells to various lymphohematopoietic cells is an in vitro model of the hematopoietic cell development during embryogenesis. To understand this process at cellular levels, differentiation intermediates were investigated. ES cells generated progeny expressing CD34, which was significantly enhanced by vascular endothelial growth factor (VEGF). The isolated CD34+ cells were enriched for myeloid colony-forming cells but not significantly for erythroid colony-forming cells. When cultured on OP9 stroma cells in the presence of interleukin-2 and interleukin-7, the CD34+ cells developed two types of B220+ CD34- lymphocytes: CD3- cytotoxic lymphocytes and CD19+ pre-B cells, and such lymphoid potential was highly enriched in the CD34+ population. Interestingly, the cytotoxic cells expressed the natural killer (NK) cell markers, such as NKR-P1, perforin, and granzymes, classified into two types, one of which showed target specificity of NK cells. Thus, ES cells have potential to generate NK-type cytotoxic lymphocytes in vitro in addition to erythro-myeloid cells and pre-B cells, and both myeloid and lymphoid cells seem to be derived from the CD34+ intermediate, on which VEGF may play an important role.

Animals↗

Enhanced expression of hepatic acyl-coenzyme A synthetase and microsomal triglyceride transfer protein messenger RNAs in the obese and hypertriglyceridemic rat with visceral fat accumulation.

The liver plays a central role in lipoprotein metabolism. In particular, very-low density lipoprotein (VLDL) is assembled in the hepatocytes and secreted into the blood circulation. The VLDL is then catabolized to low-density lipoprotein by lipoprotein lipase and hepatic triglyceride lipase. Obese subjects, especially those with visceral fat accumulation, are frequently associated with hyperlipidemia, non-insulin-dependent diabetes mellitus (NIDDM), and hypertension. The mechanism of hyperlipidemia in visceral fat obesity has not yet been elucidated. Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model of NIDDM, characterized by obesity with visceral fat accumulation, hyperlipidemia, and late-onset insulin resistance. To elucidate the mechanism of hyperlipidemia observed in OLETF rats, we focused on the production of VLDL by the liver and investigated hepatic messenger RNA (mRNA) levels of microsomal triglyceride transfer protein (MTP), acyl-coenzyme A synthetase (ACS), and apolipoprotein B (apo B), which play important roles in VLDL synthesis and secretion. In 6-week-old OLETF rats, in which insulin resistance had not been manifested, visceral fat weight was already higher and portal free fatty acid (FFA) and VLDL-triglyceride levels were elevated compared with the control rats. Hepatic ACS activity and mRNA levels, and MTP mRNA levels were also increased in OLETF rats, whereas apo B mRNA levels were similar; these results suggest that the enhanced expression of both ACS and MTP genes associated with visceral fat accumulation before developing insulin resistance may be involved in the pathogenesis of hyperlipidemia in obese animal models with NIDDM.

Adipose Tissue↗

Elevated serum levels of soluble Fas/APO-1 (CD95) in patients with hepatocellular carcinoma.

Fas (APO-1/CD95)-mediated apoptosis plays an important role in liver cell destruction in viral hepatitis. Using sandwich ELISA, we measured serum levels of soluble Fas (sFas) in patients with hepatocellular carcinoma (HCC) who were positive for hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV) antibody. sFas levels were significantly higher in HCC patients (median 4.07 ng/ml; range 0.14-29.18 ng/ml) than levels in age-matched healthy donors (0.29 ng/ml; 0-4.90 ng/ ml) (P < 0.0001) and HBsAg or anti-HCV antibody-positive patients with liver cirrhosis (LC) (2.16 ng/ ml; 0.24-8.39 ng/ml) (P = 0.0015). An arbitrary cut-off level of 3.03 ng/ml (mean + 3 s.d. of controls) revealed the positive frequency of sFas in each group: 1.7% in healthy subjects, 25.9% in LC, and 59.0% in HCC (sensitivity 59.0% and specificity 74.1%). All HCC sera tested contained transmembrane-deleted sFas and some contained another sFas lacking the Fas C-terminal. The positive frequency of either sFas (59.0%) or alpha-fetoprotein (AFP) (57.4%) in HCC patients reached 77.0%. HCC patients with multiple tumour foci (7.53 ng/ml; 1.40-29.18 ng/ml) had significantly higher sFas levels than did patients with a solitary tumour (2.70 ng/ml; 0.14-19.0 ng/ml) (P = 0.003). In all of the sFas-positive patients with a solitary tumour, surgical removal of the tumour reduced sFas levels to the negative in the first post-op week. These findings suggest that sFas may be closely linked with HCC and may be a candidate for a clinical parameter for HCC.

Adult↗

Effects of closed-system drain in surgery: focus on methicillin-resistant Staphylococcus aureus.

OBJECTIVE: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has made a strong impact on the strategy of peri-operative antibiotic prophylaxis, since MRSA has become one of the most common causative organisms of nosocomial infection in recent years. In this study, we conducted a bacteriological evaluation of surgical drains before and after introducing strategies to decrease MRSA infection rates. DESIGN AND PATIENTS: Between January 1987 and December 1994, we performed a total of 2, 755 surgical operations on inpatients, including 1,635 major and 1, 120 minor operations. Almost all surgical drains were examined bacteriologically when they were removed. The number of drains examined was 460 +/- 47 (mean +/- SEM) per year. Since the increased incidence of MRSA infection, we started exclusively using a closed drainage system and first-generation cephalosporins in 1991. The strategy was evaluated by comparing the positive rates of drain cultures, changes in bacteriological features, and incidence of MRSA infection for the 4-year periods before and after 1991. RESULTS: The positive rate of bacteria in the drains decreased significantly (p < 0.01) from 25 +/- 2 to 16 +/- 1%. Bacteriologically, the positive rate of Staphylococcus spp. decreased significantly (p < 0.05) from 7 +/- 2 to 3 +/- 0.3%. Positive rates of MRSA decreased significantly (p < 0.05) from 2.1 +/- 0.3 to 1.3 +/- 0.3%. Streptococcus declined dramatically from 3.0 +/- 0.3 to 0.3 +/- 0.1%. Of gram-negative strains, Pseudomonas and Escherichia coli were most often isolated. They showed no significant difference in positive rates between the terms. CONCLUSION: A closed drainage system and thorough use of the first-generation cephalosporins for prophylaxis were effective in decreasing positive bacterial culture of drains and reducing the incidence of MRSA on drains after surgery.

Adult↗

Changes of ischemic heart disease in Utsunomiya, Japan, over 10 years: a survey of primary care physicians.

A total of 502 patients presenting in Utsunomiya city and its suburbs during a 10-year period were studied to determine the clinical features of ischemic heart disease and to identify coronary risk factors. The male/female ratio was 1.21, but the ratio decreased with increasing age. The duration of chest pain showed a continuous spectrum between angina and infarction, with a short duration of chest pain not being useful for excluding the diagnosis of myocardial infarction. Hypertension was more common than hypercholesterolemia in this study, although the prevalence of the latter increased slightly with time, along with the shift towards a modernized occupational pattern. Smoking was a more important risk factor for ischemic heart disease in younger individuals than in the elderly, and diabetes mellitus was highly associated with the development of myocardial infarction. The incidence of radiologically diagnosed cardiac hypertrophy and aortic calcification decreased over time. These changes may have resulted in part from improved blood pressure control and the development of new anti-hypertensive and cholesterol-lowering agents.

Age Factors↗

High-resolution T2-reversed magnetic resonance imaging on a high magnetic field system. Technical note.

Because of the high signal-to-noise (S/N) ratio, T2-weighted images obtained using high-field magnetic resonance (MR) imaging systems can be expected to provide high anatomical and contrast resolution. Furthermore, the improved structural and contrast resolution of these high S/N T2-weighted images can be processed for optimum perceptual resolution through the application of gray-scale reversal and expansion of the gray-scale window, known as T2-reversed (T2R) imaging. In this study, the authors investigated high-resolution T2R MR imaging performed on a high-field (3-tesla) system for its clinical utility in detecting various physiological and pathological conditions.

Adolescent↗

[Diffusion tensor analysis with nuclear magnetic resonance in human central nervous system].

Nuclear magnetic resonance has been used to measure the diffusivity of water molecules. In central nervous system, anisotropic diffusion, which is characterized by apparent diffusion tensor Dapp zeta, is thought to be related to neuronal fiber tract orientation. For precise observation of anisotropic diffusion, it is needed to determine the diagonal and off-diagonal elements of Dapp zeta. Once Dapp zeta is estimated from a series of diffusion weighted images, a tissue's orthotropic principal axes and diffusivity of each direction are determined from eigenvalues and eigenvectors of Dapp zeta. There are several methods to represent anisotropic diffusion with Dapp zeta. Examples are diffusion ellipsoids constructed in each voxel depicting both these principal axes and the mean diffusion length in these directions, trace invariant values and its mapping image, largest eigenvalue, and ratio of largest eigenvalue to the other eigenvalue. In this study, the author investigated practical procedure to analyze diffusion tensor Dapp zeta using both of spin-echo and echo-planer diffusion weighted imagings with 3-tesla magnetic resonance machine in human brain. The ellipsoid representation provided particularly useful information about microanatomy including neuronal fiber tract orientation and molecular mobility reflective of microstructure. Furthermore, in the lesion of Wallerian degeneration, the loss of anisotropy of local apparent diffusion was observed. It is suggested that the function of axons can be observed via degree of anisotropy of apparent diffusion. Consequently, diffusion tensor analysis is expected to be a powerful, noninvasive method capable of quantitative and functional evaluation of the central nervous system.

Adult↗

Adsorption Characteristics of Silica Gels Treated with Fluorinated Silylation Agents

Branched-chain polyfluorosilane (monochlorodimethyl[4,4-bis(trifluoromethyl)-5,5,6,6,7,7,7-heptafluoroheptyl)-bonded silica gels were prepared. The surface properties of the silica gels modified with various organic silanes were evaluated by the adsorption density of polar and nonpolar gases calculated from adsorption isotherms of nitrogen, carbon dioxide, and normal butane gases. The polyfluorocarbon-bonded silica gel surface was found to be both hydrophobic and oleophobic in nature, whereas the hydrocarbon-bonded silica gel surface was characterized only as hydrophobic. The trifunctional fluorinated silane provides the silica gel surface with a more hydrophilic nature than the monofunctional silane because of the formation of a denser polymeric coating layer with a larger number of silanols.

Journal Article↗

Glucose transporter levels in a male spontaneous non-insulin-dependent diabetes mellitus rat of the Otsuka Long-Evans Tokushima Fatty strain.

Otsuka Long-Evans Tokushima Fatty (OLETF) rats are a new strain of spontaneous non-insulin-dependent diabetes mellitus (NIDDM) models. To evaluate the role of glucose transporters (GLUT) in the development of diabetes in this model, we examined the action of insulin on the translocation of GLUT4 and GLUT1 in isolated adipocytes, and the GLUT4 protein levels in muscles. Long-Evans Tokushima Otsuka (LETO) rats were used as a control strain. In adipocytes, the GLUT4 protein levels in OLETF rats at 30 weeks of age (diabetic stage) were considerably lower than those in LETO rats at the same age. At a pre-diabetic stage (7 weeks), there were no significant differences in GLUT4 protein levels in adipocytes between LETO and OLETF rats. However, the degree of GLUT4 translocation in OLETF rats was lower than that in LETO rats at 7 weeks of age. There were no differences in GLUT1 levels in adipocytes between the two strains. In muscles, the decrease in GLUT4 protein was observed in OLETF rats at 30 weeks of age. Whether such a difference is under the influence of hyperglycemia was also examined using rats rendered diabetic by 70% pancreatectomy. OLETF rats aged 7 weeks were subjected to partial pancreatectomy (Px) and sham pancreatectomy (sham). At 4 weeks after surgery, GLUT4 protein levels in adipose tissues and skeletal muscles were determined. GLUT4 decrease was observed for both tissues of hyperglycemic Px rats compared with euglycemic sham. Moreover, we examined the direct effect of glucose on GLUT4 protein using primary cultured adipocytes of OLETF rats at 5 weeks of age. After 7-day culture with normal (5.6 mmol/l) or high (25 mmol/l) concentrations of glucose, the GLUT4 protein levels in adipocytes decreased at 25 mmol/l glucose compared with 5.6 mmol/l glucose. These findings suggest an early defect in the insulin resistance of OLETF rats probably reflects impaired GLUT4 translocation. The GLUT4 decrease, which occurs later in the process appears to be a consequence, rather than a cause of diabetes in OLETF rats.

Adipocytes↗

Copper concentration in hyperintense hepatocellular carcinomas of Long-Evans cinnamon rats on T1-weighted images.

The Long-Evans Cinnamon (LEC) rat has abnormal intrahepatic copper accumulation and spontaneously develops hepatocellular carcinomas following hereditary hepatitis. The hepatocellular carcinomas are very similar to human well-differentiated hepatocellular carcinoma in histopathological features and on MR images. Copper is believed to be one of the causes of hyperintensity of hepatocellular carcinomas compared to surrounding non-cancerous tissues on T1-weighted MR image. Eight LEC rats were studied by MR imaging. We measured copper concentrations from the hepatocellular carcinomas and surrounding non-cancerous liver tissues. Signal intensity of hepatocellular carcinomas without cystic areas was iso- to slightly hyperintense relative to surrounding non-cancerous tissues on T1-weighted images. Histopathologically, most of the tumors resembled human highly or well-differentiated hepatocellular carcinomas. Copper concentrations of the hepatocellular carcinomas were lower than the surrounding non-cancerous liver tissues. Copper may not be the cause of increased signal intensity typically observed on T1-weighted images of hepatocellular carcinomas.

Animals↗

A fluorometric assay for measuring deamidase (lysosomal protective protein) using high-performance liquid chromatography.

A rapid and sensitive assay method for the determination of deamidase activity is reported. This method is based on fluorometric detection of a dansylated dipeptide, 5-dimethylaminonaphthalene-1-sulfonyl-D-Tyr-Val (N-Dns-D-Tyr-Val), enzymatically formed from the substrate 5-dimethylaminonaphthalene-1-sulfonyl-D-Tyr-Val-NH2 (N-Dns-D-Tyr-Val-NH2), after separation by high-performance liquid chromatography (HPLC) using a C-18 reversed-phase column by isocratic elution. This method is sensitive enough to measure N-Dns-D-Tyr-Val at concentrations as low as 100 fmol, yields highly reproducible results and requires less than 8.5 min per sample for separation and quantitation. The optimum pH for deamidase activity was 4.0-4.5. Greater than 5 mM of reduced glutathione was needed for maximal enzyme activity. The Km and Vmax values were respectively 125 microM and 14.12 pmol/micrograms/h with the use of enzyme extract obtained from mouse spleen. Deamidase activity was strongly inhibited by Ag+, Cu2+, diisopropylfluorophosphate, and p-chloromercuriphenylsulfonic acid. Among the organs examined in a mouse, the highest specific activity of the enzyme was found in spleen. The sensitivity and selectivity of this method will aid in efforts to examine the physiological role of this enzyme.

Animals↗

Hepatocyte growth factor and c-met expression in Long-Evans Cinnamon rats with spontaneous hepatitis and hepatoma.

The Long-Evans Cinnamon (LEC) rat is characterized by the spontaneous onset of acute and chronic hepatitis, followed by occurrence of liver cancer, and is thus able to provide a unique experimental model for human genetical liver disease, Wilson's disease. Hepatocyte growth factor (HGF) is a potent hepatotrophic factor in liver regeneration, and its expression is up-regulated in response to liver injuries. We found that the plasma HGF level in LEC rats rose markedly during the fulminant hepatitis phase, fell during the phase of chronic/cholangiofibrosis, and fluctuated during the hepatoma phase. Immunohistological staining of the liver revealed that the number of HGF-positive cells increased remarkably during the fulminant hepatitis phase, and that many of these cells were localized at the portal triads. Fewer HGF-positive cells were observed during the phase of chronic hepatitis. The surface of the hepatocellular carcinoma (HCC) cells and the cytoplasm of the nonepithelial cells in cancerous liver tissues were HGF-positive. The HGF-messenger RNA (mRNA) level in the liver rose in the fulminant hepatitis phase, fell in the chronic hepatitis phase, and was intermediate or high during the hepatoma phase. The expression of c-met mRNA was strong in the tissues of LEC rats with fulminant hepatitis and, especially, in the cholangiofibrosis tissues. c-met mRNA was also detected in HCCs. These results suggest that the HGF-c-met system may play an important role in the regeneration of hepatocytes as well as in the development of HCC in paracrine or autocrine mechanisms.

Animals↗