Biomedical subjects

Toshiyuki Maki

Publications and source records attributed to Toshiyuki Maki.

12 recordsLinked to original sources

PubMed2005

Retrograde degeneration of the corticospinal tract associated with pontine infarction.

We report a 40-year-old man with myotonic dystrophy who survived for 5 years after pontine infarction. Serial MRI detected abnormal T2 elongation of the corticospinal tract at the cerebral peduncle 4 years after the infarction. An autopsy confirmed the existence of retrograde degeneration extending from the pons to the internal capsule, evidence that retrograde degeneration in the corticospinal tract occurs above the pontine level. MRI was suggested to be useful for detection of the degenerative process.

Adult↗

PubMed2005

Production and autocrine/paracrine effects of endogenous insulin-like growth factor-1 in rat cardiac fibroblasts.

Insulin-like growth factor (IGF)-1 appears to play an important role in cardiac hypertrophy or remodeling. However, the role of endogenous IGF-1 in the growth of cardiac myocytes and fibroblasts remains unclear. This study investigated the major site of the production of cardiac IGF-1 and the local effects of endogenous IGF-1 secreted from cardiac cells. A significant expression of IGF-1 mRNA was found in cultured neonatal and adult rat cardiac fibroblasts, but not in myocytes. In addition, an in vivo examination by in situ hybridization histochemical analyses demonstrated the IGF-1 transcripts in the interstitial fibrotic tissue of the ventricle. Time-dependent secretion of IGF-1 protein was also observed in cultured cardiac fibroblasts. An antibody against IGF-1 decreased collagen synthesis in cardiac fibroblasts under basal conditions. Fibroblast-conditioned medium, as well as exogenous IGF-1, increased protein synthesis in cardiac myocytes, and this increase was inhibited by antibodies against IGF-1 and IGF-1 receptor, IGF binding protein-3, and IGF-1 receptor antagonist. These observations suggest that IGF-1 is produced and released mainly from cardiac fibroblasts and that endogenous IGF-1 promotes collagen synthesis by cardiac fibroblasts and hypertrophy of myocytes as an autocrine and a paracrine factor. Cardiac IGF-1 may function as an endogenous modulator of cardiac hypertrophy or remodeling.

Animals↗

PubMed2005

Peroxisome proliferator-activated receptor (PPAR)alpha activation increases adiponectin receptors and reduces obesity-related inflammation in adipose tissue: comparison of activation of PPARalpha, PPARgamma, and their combination.

We examined the effects of activation of peroxisome proliferator-activated receptor (PPAR)alpha, PPARgamma, and both of them in combination in obese diabetic KKAy mice and investigated the mechanisms by which they improve insulin sensitivity. PPARalpha activation by its agonist, Wy-14,643, as well as PPARgamma activation by its agonist, rosiglitazone, markedly improved insulin sensitivity. Interestingly, dual activation of PPARalpha and -gamma by a combination of Wy-14,643 and rosiglitazone showed increased efficacy. Adipocyte size in Wy-14,643-treated KKAy mice was much smaller than that of vehicle- or rosiglitazone-treated mice, suggesting that activation of PPARalpha prevents adipocyte hypertrophy. Moreover, Wy-14,643 treatment reduced inflammation and the expression of macrophage-specific genes in white adipose tissue (WAT). Importantly, Wy-14,643 treatment upregulated expression of the adiponectin receptor (AdipoR)-1 and AdipoR2 in WAT, which was decreased in WAT of KKAy mice compared with that in nondiabetic control mice. Furthermore, Wy-14,643 directly increased expression of AdipoRs and decreased monocyte chemoattractant protein-1 expression in adipocytes and macrophages. Rosiglitazone increased serum adiponectin concentrations and the ratio of high molecular weight multimers of adiponectin to total adiponectin. A combination of rosiglitazone and Wy-14,643 increased both serum adiponectin concentrations and AdipoR expression in WAT. These data suggest that PPARalpha activation prevents inflammation in WAT and that dual activation of PPARalpha and -gamma enhances the action of adiponectin by increasing both adiponectin and AdipoRs, which can result in the amelioration of obesity-induced insulin resistance.

Animals↗

PubMed2004

Insulin/Foxo1 pathway regulates expression levels of adiponectin receptors and adiponectin sensitivity.

Adiponectin/Acrp30 is a hormone secreted by adipocytes, which acts as an antidiabetic and antiatherogenic adipokine. We reported previously that AdipoR1 and -R2 serve as receptors for adiponectin and mediate increased fatty acid oxidation and glucose uptake by adiponectin. In the present study, we examined the expression levels and roles of AdipoR1/R2 in several physiological and pathophysiological states such as fasting/refeeding, obesity, and insulin resistance. Here we show that the expression of AdipoR1/R2 in insulin target organs, such as skeletal muscle and liver, is significantly increased in fasted mice and decreased in refed mice. Insulin deficiency induced by streptozotocin increased and insulin replenishment reduced the expression of AdipoR1/R2 in vivo. Thus, the expression of AdipoR1/R2 appears to be inversely correlated with plasma insulin levels in vivo. Interestingly, the incubation of hepatocytes or myocytes with insulin reduced the expression of AdipoR1/R2 via the phosphoinositide 3-kinase/Foxo1-dependent pathway in vitro. Moreover, the expressions of AdipoR1/R2 in ob/ob mice were significantly decreased in skeletal muscle and adipose tissue, which was correlated with decreased adiponectin binding to membrane fractions of skeletal muscle and decreased AMP kinase activation by adiponectin. This adiponectin resistance in turn may play a role in worsening insulin resistance in ob/ob mice. In conclusion, the expression of AdipoR1/R2 appears to be inversely regulated by insulin in physiological and pathophysiological states such as fasting/refeeding, insulin deficiency, and hyper-insulinemia models via the insulin/phosphoinositide 3-kinase/Foxo1 pathway and is correlated with adiponectin sensitivity.

Adenoviridae↗

PubMed2004

Insulin receptor substrate 2 plays a crucial role in beta cells and the hypothalamus.

We previously demonstrated that insulin receptor substrate 2 (Irs2) KO mice develop diabetes associated with hepatic insulin resistance, lack of compensatory beta cell hyperplasia, and leptin resistance. To more precisely determine the roles of Irs2 in beta cells and the hypothalamus, we generated beta cell-specific Irs2 KO and hypothalamus-specific Irs2 knockdown (betaHT-IRS2) mice. Expression of Irs2 mRNA was reduced by approximately 90% in pancreatic islets and was markedly reduced in the arcuate nucleus of the hypothalamus. By contrast, Irs2 expression in liver, muscle, and adipose tissue of betaHT-IRS2 mice was indistinguishable from that of control mice. The betaHT-IRS2 mice displayed obesity and leptin resistance. At 4 weeks of age, the betaHT-IRS2 mice showed normal insulin sensitivity, but at 8 and 12 weeks, they were insulin resistant with progressive obesity. Despite their normal insulin sensitivity at 8 weeks with caloric restriction, the betaHT-IRS2 mice exhibited glucose intolerance and impaired glucose-induced insulin secretion. beta Cell mass and beta cell proliferation in the betaHT-IRS2 mice were reduced significantly at 8 and 12 weeks but not at 10 days. Insulin secretion, normalized by cell number per islet, was significantly increased at high glucose concentrations in the betaHT-IRS2 mice. We conclude that, in beta cells and the hypothalamus, Irs2 is crucially involved in the regulation of beta cell mass and leptin sensitivity.

Animals↗

PubMed2003

Direct inhibition of neutral endopeptidase in vasopeptidase inhibitor-mediated amelioration of cardiac remodeling in rats with chronic heart failure.

Vasopeptidase inhibitors possess dual inhibitory actions on neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) and have beneficial effects on cardiac remodeling. However, the contribution of NEP inhibition to their effects is not yet fully understood. To address the role of cardiac NEP inhibition in the anti-remodeling effects of a vasopeptidase inhibitor, we examined the effects of omapatrilat on the development of cardiac remodeling in rats with left coronary artery ligation (CAL) and those on collagen synthesis in cultured fibroblast cells. In vivo treatment with omapatrilat (30 mg/kg/day for 5 weeks) inhibited cardiac NEP activity in rats with CAL, which was associated with a suppression of both cardiac hypertrophy and collagen deposition. In cultured cardiac fibroblasts, omapatrilat (10(-7) to approximately 10(-5) M) inhibited NEP activity and augmented the ANP-induced decrease in [3H]-proline incorporation. ONO-BB, an active metabolite of the NEP selective inhibitor ONO-9902, also augmented the ANP-induced response, whereas captopril, an ACE inhibitor, did not. The angiotensin I-induced increase in [3H]-proline incorporation was prevented by omapatrilat and captopril, but not by ONO-BB. The results suggest that vasopeptidase inhibitor suppressed cardiac remodeling in the setting of chronic heart failure, possibly acting through the direct inhibition of cardiac NEP. Vasopeptidase inhibitors may have therapeutic advantages over the classical ACE and NEP inhibitors alone with respect to the regression of cardiac fibrosis.

Animals↗

PubMed2003

Beneficial effects of sampatrilat, a novel vasopeptidase inhibitor, on cardiac remodeling and function of rats with chronic heart failure following left coronary artery ligation.

Sampatrilat is a novel vasopeptidase inhibitor that may offer a greater benefit than traditional angiotensin-converting enzyme (ACE) inhibitors in the treatment of chronic heart failure (CHF). The present study was undertaken to determine whether sampatrilat improves hemodynamic function and cardiac remodeling through a direct action on the failing heart in rats with CHF following left coronary artery ligation (CAL). Sampatrilat (30 mg/kg a day) was administered orally to the animals from the 1st to 6th week after the operation. Sampatrilat reduced the mortality of the rats with CAL (20 versus 57% for untreated rats). Treatment with sampatrilat for 5 weeks suppressed tissue ACE and neutral endopeptidase (NEP) activities. Sampatrilat did not affect the arterial blood pressure, whereas it attenuated the CAL-induced increases in the left ventricular end-diastolic pressure, heart weight, and collagen content of the viable left ventricle. To assess the direct effects of sampatrilat on collagen synthesis, we measured the incorporation of [(3)H]proline into cultured cardiac fibroblasts. Sampatrilat at concentrations that inhibited NEP activity in vitro augmented the atrial natriuretic peptide-induced decrease in [(3)H]proline incorporation by the cells. In addition, sampatrilat prevented the angiotensin I-induced increase in [(3)H]proline incorporation, whereas captopril did not. The results suggest that long-term treatment with sampatrilat regresses cardiac remodeling in rats with CAL, which is associated with improvement of hemodynamic function. The mechanism by which sampatrilat improved cardiac remodeling may be attributable to the direct inhibition of cardiac fibrosis, possibly acting through the cardiac natriuretic peptide system.

Animals↗

PubMed2003

Gene expression, secretion, and autocrine action of C-type natriuretic peptide in cultured adult rat cardiac fibroblasts.

C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is known to be synthesized in the central nervous system and vascular endothelial cells, in contrast to atrial natriuretic peptide and brain natriuretic peptide. However, there have been no studies concerning CNP production in cultured cardiac cells. Here, we examined the production and the local effect of CNP in cultured ventricular cells. Under serum-free conditions, adult rat cardiac fibroblasts secreted immunoreactive CNP time dependently. TGF-beta1, basic fibroblast growth factor, and endothelin-1 significantly stimulated CNP secretion. Northern blot analysis detected significant expressions of CNP and its specific receptor (guanylyl cyclase-B) mRNA in cardiac fibroblasts. CNP stimulated intracellular cGMP production in fibroblasts more intensely than atrial and brain natriuretic peptides. CNP inhibited both DNA and collagen syntheses of cardiac fibroblasts, and these inhibitory effects by CNP were stronger than by atrial and brain natriuretic peptides. The inhibition by CNP of DNA and collagen syntheses was reproduced by a cGMP analog, 8-bromo cGMP. The present findings demonstrate that CNP is synthesized in and secreted from cardiac fibroblasts and suggest that CNP has a suppressive effect on fibroblast proliferation and extracellular matrix production, probably via the guanylyl cyclase-B-mediated cGMP-dependent process. CNP produced by cardiac fibroblasts may play a role as an autocrine regulator against excessive cardiac fibrosis.

Age Factors↗

PubMed2002

Disturbance-free high-speed sinusoidal phase-modulating laser diode interferometer.

A surface profiler that incorporates a feedback controller to eliminate external disturbances is proposed and demonstrated. Its overall performance is dependent on the frequency response of the feedback loop. The frequency of the modulating signal strongly influences the response of the feedback controller. When we used the integrating-bucket method, the CCD camera had to be operated at a low-frequency video rate. Our technique uses a CCD camera equipped with an electronic shutter. The shutter function enables us to apply high-speed sinusoidal phase modulation to the conventional integrating-bucket method under the standard video rate.

Journal Article↗

PubMed2002

Utilization behavior as a white matter disconnection syndrome.

We report a case of utilization behavior that was examined neuropathologically. A 72-year-old right-handed male patient, who was admitted with a complaint of transient loss of consciousness, displayed utilization behavior several times. He used daily objects that were placed in front of him, such as a teacup and a toothbrush, without instructions to do so. If the examiner asked the patient not to use the objects, the patient did not use them. MRI revealed acute infarction of the left superior frontal gyrus, where decreased blood flow was revealed by SPECT. The patient died of an acute worsening of dilated cardiomyopathy. Neuropathological examination demonstrated an acute phase infarction of the subcortical white matter of the left superior frontal lobe, which correlated well with neuroradiological findings. Utilization behavior has been thought a "frontal lobe symptom". However, we propose that utilization behavior might be considered a white matter disconnection syndrome.

Aged↗

PubMed2002

Effects of tanshinone VI on the hypertrophy of cardiac myocytes and fibrosis of cardiac fibroblasts of neonatal rats.

The possible effects of tanshinone VI (tsh), a diterpene from the root of Tan-Shen (Salvia miltiorrhiza, Bunge (Labiatae)) on hypertrophy and fibrosis in cultured neonatal rat cardiac myocytes and fibroblasts were examined. Tsh had no significant effect on protein synthesis, which was evaluated by [3H]-leucine incorporation into the acid insoluble fraction in the cells, in the absence of stimulatory factors in cardiac myocytes. The amount of protein produced in cardiac myocytes was increased by 10(-8) M endothelin-1 (ET-1), 10(-6) M phenylephrine (PE), or 10(-8) M insulin-like growth factor-1 (IGF-1), suggesting that hypertrophy of cardiac myocytes in vitro was induced by these factors. The ET-1-, PE-, or IGF-1-induced increase in protein synthesis was attenuated by treatment with 10(-5) M tsh. Treatment with 10(-5) M tsh significantly decreased the synthesis of collagen by cardiac fibroblasts, which was evaluated by [3H]-proline incorpolation into acid-insoluble fraction of the fiblobrasts, in the absence of stimulatory factors for the production. Fetal bovine serum (FBS) or IGF-1 increased collagen synthesis in a concentration-dependent manner. The increase at 5% FBS or 10(-8) M IGF-1 was inhibited by 10(-5) M tsh. Fibroblast-conditioned medium (FB-CM) increased protein synthesis in cardiac myocytes in a concentration-dependent manner (10; - 100 %). Tsh attenuated the FB-CM-induced increase in protein synthesis by cardiac myocytes. These results show that tsh may attenuate the humoral factor-induced hypertrophy of cardiac myocytes and fibrosis of cardiac fibroblasts. The findings suggest that tsh may improve the development of cardiac remodeling under pathophysiological conditions. Abbreviations. ANP:atrial natriuretic peptide DMEM:Dulbecco-modified Eagle's medium ET-1:endothelin-1 FB-CM:fibroblast-conditioned medium FBS:fetal bovine serum IGF-1:insulin-like growth factor-1 PE:phenylephrine tsh:tanshinone VI

Animals↗

PubMedDate not supplied

Magnetic resonance imaging findings of Machado-Joseph disease: histopathologic correlation.

PURPOSE: To determine the characteristic magnetic resonance imaging (MRI) findings of early- and late-stage Machado-Joseph disease (MJD) and to examine correlation with pathologic specimens. PATIENTS AND METHODS: Four patients genetically diagnosed with MJD and a familial case of MJD were all examined using MRI. Machado-Joseph disease was pathologically confirmed in one of the four genetically diagnosed patients, and the findings were compared with the MRI results. RESULTS: In all three patients who had MJD for less than 8 years, MRI confirmed mild cerebellar atrophy, particularly in the vermis, and atrophic changes in the superior cerebellar peduncle. Mild pontine atrophy was observed in these three patients. Atrophic changes in the pontine tegmentum were more prominent than those of the pontine base in these patients. Two of the three patients showed mild frontal atrophy. Of the five total patients, two had the disease for over 10 years and showed progressive atrophy of the brainstem and mild frontal atrophy. These two patients also showed pallidal atrophy. One autopsied case in which the disease duration was 17 years showed a typical pathologic picture of MJD. Macroscopic findings for this patient showed marked atrophy of the pons, mild cerebellar atrophy (particularly in the vermis), marked atrophy of the superior cerebellar peduncle, severe involvement of motor nuclei, and atrophy and discoloration of the pallidum and subthalamic nuclei. CONCLUSION: In the early stages of MJD, mild pontine atrophy, particularly in the tegmentum, and mild cerebellar atrophy are typical MRI findings. Atrophic changes in the brainstem may be progressive. Pallidal atrophy may be observed in patients with long disease duration. These findings correlated with the pathologic findings.

Adult↗