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Biomedical subjects

T Nakata

Publications and source records attributed to T Nakata.

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

Reduction of insulin resistance attenuates the development of hypertension in sucrose-fed SHR.

We examined the effect of pioglitazone, a thiazolidinedione derivative that increases insulin sensitivity without increasing insulin secretion, on the development and maintenance of hypertension in sucrose-fed SHR. Nine-week-old male SHR received 12% sucrose dissolved in tap water as drinking water. For 5 weeks, half of the rats were given regular rat chow, and the rest were fed with rat chow containing 0.03% pioglitazone. In week 6, blood glucose and plasma insulin levels were examined before and after oral glucose administration by gavage. Sucrose treatment elicited a significant elevation of systolic blood pressure 3 weeks after the beginning of treatment; pioglitazone treatment attenuated this elevation. The insulin resistance and hyperinsulinemia observed in sucrose-fed SHR were prevented by pioglitazone treatment. Pioglitazone treatment also significantly reduced the urinary excretion of catecholamines and plasma renin activity, both of which were significantly greater in sucrose-fed SHR than in control SHR. Along with improving insulin sensitivity, pioglitazone treatment also attenuated the development of hypertension in SHR fed the regular rat chow, but not in WKY rats. These results indicate that insulin resistance and hyperinsulinemia play an important role in the development of hypertension in SHR probably through the activation of the renin-angiotensin system and sympathetic nervous outflow. This study also shows that chronic sucrose treatment exacerbated the development of hypertension through these mechanisms, precipitating insulin resistance.

Animals↗
PubMed1997

Bruceine B, a potent inhibitor of leukocyte-endothelial cell adhesion.

Leukocyte adhesion to vascular endothelial cells is an essential step in the development of inflammatory diseases. We have searched for inhibitors of leukocyte-endothelial cell adhesion that could be used as anti-inflammatory drugs and found that bruceine B (0.2 microgram/ml; 0.44 microM) inhibited human neutrophil or T cell adhesion to tumor necrosis factor-alpha (TNF) stimulated human umbilical vein endothelial cells (HUVEC). The inhibition of neutrophil adhesion to TNF-stimulated HUVEC by bruceine B was not derived from cytotoxic effects, as determined by measurement of the level of lactate dehydrogenase (LDH) activity in conditioned medium. The effect of bruceine B on neutrophil adhesion to HUVEC was not seen when the neutrophils were preincubated with bruceine B. However, inhibitory effects were evident when the HUVEC were preincubated with bruceine B. Bruceine B also inhibited neutrophil adhesion to lipopolysaccharide-stimulated HUVEC and T cell adhesion to TNF-stimulated HUVEC. These findings suggest that bruceine B may have anti-inflammatory activity.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Crossover trial of simvastatin versus pravastatin in patients with primary hypercholesterolemia.

The effects of simvastatin and pravastatin administered alone at initial doses of 5 and 10 mg/day, respectively, on normalization of abnormal lipid metabolism in patients with hypercholesterolemia were evaluated by a crossover method. Patients whose serum levels of total cholesterol (TC) were > or = 220 mg/dl were randomly divided into two groups, and one of the groups (group S-P: 17 patients) was treated with simvastatin first and then with pravastatin whereas the other group (group P-S: 19 patients) was treated with pravastatin first and then with simvastatin. Simvastatin or pravastatin was replaced with the other drug after 8-week administration in each group. These drugs were administered for 8 weeks each. Simvastatin and pravastatin significantly reduced the following serum lipids as compared with the levels in the observation period: TC by 23.2 +/- 8.1% and 18.1 +/- 10.9%, triglyceride (TG) by 13.0 +/- 24.7% and 5.8 +/- 47.1%, and low-density lipoprotein cholesterol (LDL-C) by 31.3 +/- 10.1% and 23.1 +/- 14.3%, respectively. TC and LDL-C levels were significantly (p < 0.001) lower and decreased to significantly (p < 0.001) greater degrees after simvastatin treatment than after pravastatin treatment. TC was normalized in 77.8% of the patients (28 of 36) after simvastatin treatment and in 68.9% of the patients (23 of 36) after pravastatin treatment. LDL-C was normalized in 63.9% of the patients (23 of 36) after simvastatin treatment and in 44.4% of the patients (16 of 36) after pravastatin treatment. The percentage of patients whose LDL-C was normalized by simvastatin was significantly (p < 0.05) higher as compared with pravastatin. Results of this trial, which was conducted by a crossover method, show that the initial dose of simvastatin reduces serum cholesterol and LDL-C more potently than the initial dose of pravastatin in patients with hypercholesterolemia.

Adult↗
PubMed1997

Pulsatile compression of the rostral ventrolateral medulla in hypertension.

The rostral ventrolateral medulla (RVLM) has been known to be a major regulating center of sympathetic and cardiovascular activities. An association between essential hypertension and neurovascular compression of the RVLM has been reported in clinical observations, including magnetic resonance imaging (MRI) studies. To reconfirm this relationship, we performed MRI using a high-resolution 512 x 512 matrix in patients with essential and secondary hypertension and in normotensive subjects. The duration of hypertension and the degree of organ damage by hypertension were not significantly different between the two hypertension groups. Neurovascular compression of the RVLM was observed in 74% of the essential hypertension group, and the incidence of compression was significantly higher than in the secondary hypertension group (11%) or in the normotensive group (13%) (P < .01). These results from the clinical studies suggest that neurovascular compression of the RVLM is, at least in part, causally related to essential hypertension. Although blood pressure elevation by pulsatile compression of the RVLM in an experimental baboon model has already been reported, its underlying mechanism is not well known. Accordingly, we performed experiments to investigate whether pulsatile compression of the RVLM would increase arterial pressure and to elucidate the mechanism of the pressor response in rats. Sympathetic nerve activity, arterial pressure, heart rate, and plasma levels of epinephrine and norepinephrine were increased by pulsatile compression of the RVLM. The pressor response was abolished by intravenous treatment with hexamethonium or RVLM injection of kainic acid. In summary, the results from the MRI studies suggest that neurovascular compression of the RVLM is, at least in part, causally related to essential hypertension. This was supported by the results from experimental studies using rats indicating that pulsatile compression of the RVLM increases arterial pressure by enhancing sympathetic outflow.

Animals↗
PubMed1997

Neurovascular compression of the rostral ventrolateral medulla related to essential hypertension.

The rostral ventrolateral medulla (RVLM) is thought to serve as a final common pathway for the integration of central cardiovascular information and to be important for the mediation of central pressor responses. An association between essential hypertension and neurovascular compression of the RVLM has been reported. To confirm this relationship and to quantitatively measure the distances between the RVLM and the neighboring arteries, we performed magnetic resonance imaging using a high-resolution 512x512 matrix and magnetic resonance angiography in 49 subjects (21 patients with essential hypertension, 10 patients with secondary hypertension, and 18 normotensive subjects). One patient with essential hypertension was excluded from the evaluations because of inadequate assessment due to poor images. Neurovascular compression of the RVLM was observed in 15 of 20 (75%) patients with essential hypertension. In contrast, neurovascular compression was observed in only 1 of 10 (10%) patients with secondary hypertension and only 2 of 18 (11%) normotensive subjects. The rate of observed neurovascular compression in the essential hypertension group was significantly higher than that in the secondary hypertension group and the normotensive group (P<.01 for both). The distances between the RVLM and the nearest arteries in the essential hypertension group were significantly shorter than those in the other groups (P<.05 for all). On the other hand, the distances between the surface of the medulla oblongata and the nearest arteries did not differ among these three groups. These results suggest that neurovascular compression of the RVLM, but not of the other regions of the medulla oblongata, is particularly related to essential hypertension.

Adult↗
PubMed1997

Chronic angiotensin blockade with candesartan cilexetil in DOCA/salt hypertensive rats reduces cardiac hypertrophy and coronary resistance without affecting blood pressure.

To determine whether angiotensin II participates in the pathogenesis of cardiac hypertrophy and impairs coronary circulation in DOCA/salt hypertension, DOCA hypertensive rats were treated with candesartan cilexetil for 8 wk. DOCA/salt hypertension was induced in Wistar rats by removing the right kidney and subcutaneously injecting deoxycorticosterone acetate once a week. Control rats were given subcutaneous injections of saline and maintained on a normal diet. After 4 wk of observation, the angiotensin II receptor antagonist candesartan cilexetil was administered by oral gavage for 8 wk to 14 rats. Systolic blood pressure was measured weekly with the tail-cuff method. After 12 wk, the rats were killed and prepared. The isolated hearts were perfused by a Langendorff apparatus at constant flow. Perfusion pressure was measured by a small-volume transducer, and perfusion flow was recorded by a drop counter. Development of hypertension was not prevented by candesartan cilexetil treatment, but development of cardiac hypertrophy was inhibited. Minimum coronary vascular resistance (MCVR) obtained upon infusing adenosine into the isolated hearts was significantly higher in DOCA/salt hypertensive rats than in sham-operated controls. The elevated MCVR in DOCA/salt hypertensive rats was decreased by the administration of candesartan cilexetil for 8 wk. Thus, candesartan cilexetil regressed cardiac hypertrophy and improved coronary vascular resistance without affecting high blood pressure. These findings suggest that angiotensin II plays an important role in the pathogenesis of cardiac hypertrophy in DOCA/salt hypertension and that cardiac hypertrophy increases coronary vascular resistance.

Angiotensin Receptor Antagonists↗
PubMed1997

Appropriate hematocrit levels of erythropoietin supplementary therapy in end-stage renal failure complicated by coronary artery disease.

OBJECTIVE: To investigate an appropriate hematocrit (Hct) for managing renal anemia complicated by angina pectoris at rest. DESIGN: Nonrandomized, retrospective and prospective observational study. SETTING: Sapporo Medical University Hospital, Sapporo, Japan. PATIENTS: Thirty-two anemic patients (aged 62 +/- 10 years, range 40 to 78) with rest angina in end-stage renal failure. INTERVENTIONS: Serial changes of exercise tolerance (estimated metabolic equivalents [METs] on stress electrocardiography produced by improvement of patients' Hct, using recombinant human erythropoietin (rHuEPO). Adverse effects, such as deteriorating systemic hypertension, were investigated with regard to the severity of coronary arteriographic findings (Leaman's score) and cardiac events within a six-month period. MAIN RESULTS: Higher Hct was clearly correlated with better estimated METs: when Hct was less than 20%, MET was 1.4 +/- 0.5; with 20% < or = Hct < 25% 2.1 +/- 1.4; with 25% < or = Hct < 30% 3.1 +/- 1.6; and with 30% < or = Hct < 35% 4.9 +/- 1.1. Patients with cardiac events (elective balloon angioplasty [n = 5], bypass surgery [n = 1], myocardial infarction [n = 2] and hospital death from congestive heart failure [n = 3]) had advanced coronary lesions compared with patients without coronary events (Leaman's score 15.9 +/- 9.3 versus 7.3 +/- 4.4, respectively, P < 0.01) and lower exercise capacity at 25% < or = Ht < 30% (estimated METs 2.4 +/- 1.2 versus 3.9 +/- 1.9, respectively, P < 0.05). Moreover, there was an inverse linear correlation between estimated METs and Leaman's score only when Hct was over 25%. In prospectively examined subjects (n = 16), Hct 35% or greater without systemic hypertension was obtained in only seven (44%), and no additional effect on exercise tolerance was expected when Hct was 35% or greater. CONCLUSIONS: Managing renal anemia with 30% < or = Hct < 35% with rHuEPO is considered an appropriate therapy in patients with end-stage renal failure complicated by rest angina.

Adult↗
PubMed1997

Sustained right ventricular dyskinesis complicated by right ventricular infarction.

We encountered a 66-yr-old man with acute left inferior and right ventricular infarction. Tomographic radionuclide ventriculography and Fourier analysis clearly demonstrated reduced wall motion in the inferior walls of both ventricles and markedly delayed phase angles in the inferior right ventricular segment, indicating dyskinesis, which was confirmed by two-dimensional echocardiography and contrast right ventriculography. Four years later, right ventricular dyskinesis was still present and corresponded to a right ventricular perfusion defect on 99mTc-labeled tetrofosmin tomogram. Right ventricular imaging with tomographic radionuclide ventriculography with Fourier analysis and 99mTc-labeled myocardial tomography demonstrates that, even after improved global function and hemodynamics, right ventricular dyskinesis related to right ventricular perfusion defect can be sustained for several years. Thus, these imaging techniques may contribute to diagnosing right ventricular infarction and investigating the pathophysiology.

Aged↗
PubMed1997

[A family with facioscapulohumeral muscular dystrophy and hereditary long QT syndrome].

We describe a family with facioscapulohumeral muscular dystrophy (FSHD) and hereditary long QT syndrome (LQT) for three generations. The proband, a 50-year-old woman, had noticed difficulty in raising the upper extremities since the age of 40. At the age of 48, she was admitted to our hospital because of arrhythmia attack. She, her mother, and one of her three children were diagnosed as having LQT. These three individuals and the proband's two siblings were clinically diagnosed as having FSHD which was confirmed by genetic analysis using EcoR1. FSHD is an autosomal dominant disorder and the gene locus is mapped to chromosome 4q35-ter, but the gene has not been isolated. LQT is a group of disorders which cause syncope and sudden death from ventricular arrhythmia in an autosomal dominant fashion. Four loci for this syndrome (LQT1-4) have been known, and three of the genes have been shown to encode ion-channels. Genetic analysis of the proband failed to detect any of previously known mutations in the LQT1, LQT2, and LQT3 genes. The locus for LQT4 has been mapped to chromosome 4q25-7. There have so far been no report of FSHD associated with LQT. Although the pathogenesis is unclear, we speculate that these two diseases are linked each other on chromosome 4q.

Chromosomes, Human, Pair 4↗
PubMed1996

Visualization of slow axonal transport in vivo.

In axons, cytoskeletal constituents move by slow transport. However, it remains controversial whether axonal neurofilaments are dynamic structures in which only subunits are transported or whether filaments assemble in the proximal axon and are transported intact as polymers to the axon terminus. To investigate the form neurofilament proteins take during transport, neurons of transgenic mice lacking axonal neurofilaments were infected with a recombinant adenoviral vector encoding epitope-tagged neurofilament M. Confocal and electron microscopy revealed that the virally encoded neurofilament M was transported in unpolymerized form along axonal microtubules. Thus, neurofilament proteins are probably transported as subunits or small oligomers along microtubules, which are major routes for slow axonal transport.

Adenoviridae↗
PubMed1996

Cloning and characterization of KAP3: a novel kinesin superfamily-associated protein of KIF3A/3B.

We previously reported that KIF3A and KIF3B form a heterodimer that functions as a microtubule-based fast anterograde translocator of membranous organelles. We have also shown that this KIF3A/3B forms a complex with other associated polypeptides, named kinesin superfamily-associated protein 3 (KAP3). In the present study, we purified KAP3 protein by immunoprecipitation using anti-KIF3B antibody from mouse testis. Microsequencing was carried out, and we cloned the full-length KAP3 cDNA from a mouse brain cDNA library. Two isoforms of KAP3 exist [KAP3A (793 aa) and KAP3B (772 aa)], generated by alternative splicing in the carboxyl terminus region. Their amino acid sequences have no homology with those of any other known proteins, and prediction of their secondary structure indicated that almost the entire KAP3 molecule is alpha-helical. We produced recombinant KAP3 and KIF3A/3B using a baculovirus-Sf9 expression system. A reconstruction study in Sf9 cells revealed that KAP3 is a globular protein that binds to the tail domain of KIF3A/3B. The immunolocalization pattern of KAP3 was similar to that of KIF3A/3B in nerve cells. In addition, we found that KAP3 does not affect the motor activity of KIF3A/3B. KAP3 was associated with a membrane-bound form of KIF3A/3B in a fractional immunoprecipitation experiment, and since the KIF3 complex was found to bind to membranous organelles in an EM study, KAP3 may regulate membrane binding of the KIF3 complex.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Regional cardiac sympathetic nerve dysfunction and the diagnostic efficacy of metaiodobenzylguanidine tomography in stable coronary artery disease.

The present study endeavors to correlate regional myocardial sympathetic nerve dysfunction with reversible and persistent perfusion abnormalities and depressed regional wall motion, and to determine the diagnostic efficacy of radio-iodinated metaiodobenzylguanidine (MIBG) tomography for detecting coronary artery disease. In 28 consecutive patients with stable coronary artery disease and 7 patients with atypical chest pain but no coronary stenosis, regional MIBG uptake was semiquantitatively evaluated in 13 left ventricular segments early (30 minutes) and late (4 hours) after injection. Regional MIBG uptake was reduced in 68 of 90 segments (76%) showing reversible perfusion abnormality and 72 of 81 segments (89%) showing persistent abnormality 4 hours after injection. Although the sensitivity and negative predictive values of late MIBG scanning for detecting myocardial perfusion abnormalities were relatively high (82% and 85%, respectively), the specificity, positive predictive value, and kappa value were low (63%, 57%, and 0.41, respectively). Right coronary lesions were detected by late MIBG scanning with a high sensitivity (85%) but a low specificity (41%). Conversely, the sensitivities for detecting lesions in the other 2 major left coronary arteries were low (55%). The overall diagnostic accuracy of late MIBG scanning was 66% and the positive and negative predictive values and kappa value were low; 60%, 70%, and 0.31, respectively. Similarly, regional sympathetic dysfunction was observed in 42 of 49 asynergic segments (86%) on late MIBG scans, of which 32 segments were viable and 10 nonviable; but the low specificity (73%) and positive predictive value (44%) reduced the kappa value (0.43). Thus, regional cardiac sympathetic innervation is impaired in ischemic, asynergic but noninfarcted myocardium as well as in myocardium which is infarcted or has a persistent perfusion abnormality. The diagnostic efficacy of MIBG tomography to detect coronary artery disease, however, is limited probably because of nonspecific reductions of MIBG uptake in the inferior and posterolateral regions.

3-Iodobenzylguanidine↗
PubMed1996

Transgenic expression of L-gulono-gamma-lactone oxidase in medaka (Oryzias latipes), a teleost fish that lacks this enzyme necessary for L-ascorbic acid biosynthesis.

Transfer of the gene for L-gulono-gamma-lactone oxidase, the missing enzyme in L-ascorbic acid biosynthesis in scurvy-prone animals, into medaka (Oryzias latipes) was successfully done. The expression plasmid pSVL-GLO, carrying rat liver L-gulono-gamma-lactone oxidase cDNA, was microinjected into the cytoplasm of fertilized eggs during the one-cell stage. Four male F0 fish having the transgene in their germ cells came to maturity, and F1 progeny derived from one of the F0 fish possessed L-gulono-gamma-lactone oxidase activity, indicating that the transgene was functionally expressed in the fish. Genomic Southern blot analysis demonstrated that the transgene existed in both chromosome-integrated and extrachromosomal forms.

Animals↗
PubMed1996

The effect of combination splenectomy and low-dose FK506 therapy on graft survival after liver allograft transplantation in rats.

The effect of splenectomy on allograft survival was investigated using orthotopic liver transplantation in a rat experimental model (ACI rat liver grafted to LEW rat). Control rats without any immunosuppressive treatment died, on average, 10.4 +/- 1.4 days after operation. Splenectomy alone somewhat prolonged the survival (13.4 +/- 2.0 days), and low-dose FK506 therapy moderately prolonged it (22.7 +/- 7 days). The graft survival period was significantly prolonged (39.7 +/- 6.3 days) when them two treatments were combined. The elevation of cytotoxic antiallograft antibodies was suppressed by splenectomy but not by low-dose FK506 therapy. The development of jaundice was moderately suppressed by FK506 but not by splenectomy. There was no difference between the pattern of body weight decline in either of them two groups and that in control rats. When these two treatments were combined at the same time, the elevation of cytotoxic antibodies, development of jaundice and decline of body weight were suppressed. These data indicate that B cells play an important role in the acute rejection of the rat liver allograft at least partially via production of cytotoxic antiallograft antibody. Splenectomy or other immunosuppressive methods affecting B cells can be a supplement for immunosuppression when using reduced-dose FK506.

Animals↗
PubMed1996

Postischemic functional recovery and BMIPP uptake after primary percutaneous transluminal coronary angioplasty in acute myocardial infarction.

To correlate asynergic wall motion after primary percutaneous transluminal coronary angioplasty with myocardial perfusion and fatty acid metabolism, quantitative tomographies using thallium and radioiodinated 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) were performed during the acute and recovery stages in 56 consecutive patients with acute myocardial infarction, of whom 32 underwent primary percutaneous transluminal coronary angioplasty (group A) and 24 were conservatively treated (group B); 44 patients (79%) had 1-vessel disease. Reduced myocardial uptakes of thallium and BMIPP and regional wall motion were quantified with a bull's eye technique and a centerline method using contrast left ventriculography, respectively. BMIPP activity was significantly lower than that of thallium at an acute stage in both groups. Abnormal BMIPP activities and the difference in thallium and BMIPP abnormalities (perfusion metabolism mismatch) at an acute stage decreased significantly during follow-up in group A (111 +/- 13 to 99 +/- 12 and 30 +/- 10 to 15 +/- 10, respectively), and not in group B (129 +/- 31 vs 118 +/- 29 and 29 +/- 13 vs 30 +/- 10, respectively). Improvement in regional wall motion abnormality correlated closely with the improved uptakes of thallium and BMIPP (y = 0.64x + 26.4, r = 0.56, p < 0.05; y = 1.1x + 11.1, r = 0.81, p < 0.001; respectively). The mismatched uptake of both tracers at an acute stage was significantly related to recovery from asynergic wall motion during follow-up in group A (y = 0.45x + 13.9, r = 0.65, p < 0.005). In conclusion, despite restored myocardial perfusion by primary coronary angioplasty, BMIPP uptake is impaired in salvaged myocardium at an acute stage of infarction. However, the degree and improvement of perfusion metabolism mismatch in acute myocardial infarction may reflect subsequent recovery from postischemic wall motion abnormality in metabolically impaired but viable myocardium after coronary reperfusion.

Adult↗
PubMed1996

Prognosis of hypertrophic cardiomyopathy: assessment by 123I-BMIPP (beta-methyl-p-(123I)iodophenyl pentadecanoic acid) myocardial single photon emission computed tomography.

123I-BMIPP (beta-methyl-iodophenyl pentadecanoic acid) has shown unique properties for potential use in assessing myocardial metabolism. Previous basic and clinical studies demonstrated that the disturbances of myocardial metabolism precede the occurrence of myocardial perfusion abnormalities by using 201Tl in hypertrophic myocardium. The present study was therefore undertaken to determine whether or not 123I-BMIPP myocardial SPECT is useful in predicting the prognosis of hypertrophic cardiomyopathy (HCM) in 65 patients in 6 facilities. There were 33 patients with non-obstructive HCM, 12 with obstructive HCM, 12 with apical HCM and 8 with dilated-phase HCM. Fasted patients at rest received an intravenous injection of 111 MBq of 123I-BMIPP. Twenty to thirty minutes later, myocardial SPECT was carried out. The BMIPP severity score (BMIPP SS) was evaluated semiquantitatively by using representative short axial SPECT images. We followed up the incidence of cardiac events for a mean period of 3.0 +/- 0.6 years. Cardiac events occurred in 13 patients. Of these, 11 developed heart failure and 6 died (4 from heart failure and 2 from sudden death). The BMIPP SS in the dilated-phase HCM was significantly lower than that for the nonsurvivors. The BMIPP SS was particularly high in patients with fatal heart failure. Furthermore, there was a close negative correlation between the BMIPP SS and percent fractional shortening measured by echocardiography (r = -0.49). Finally, the mortality over the three years increased according to the extent of the BMIPP SS. In conclusion, these results indicate that BMIPP SS is useful in evaluating the severity of HCM. We conclude that 123I-BMIPP is a valuable metabolic tracer in predicting the outcome of HCM.

Adult↗