PubMed Health⌕ Search

Biomedical subjects

Jiro Nakamura

Publications and source records attributed to Jiro Nakamura.

At least 19 recordsLinked to original sources
PubMed2006

Protein kinase C attenuates beta-adrenergic receptor-mediated lipolysis, probably through inhibition of the beta1-adrenergic receptor system.

Lipolysis in rat white adipocytes is stimulated by beta-adrenergic agonists. Phorbol 12-myristate 13-acetate (PMA) attenuated the receptor-mediated lipolysis by causing a shift of the dose-response curve to the higher concentrations of norepinephrine and isoproterenol. Although the adipocytes possess beta1-, beta2-, and beta3-adrenergic receptor subtypes, the effect of PMA was observed only when a beta1-agonist (dobutamine) was used. No lipolysis-attenuating effect of PMA was found when cells were exposed to a beta2-agonist (procaterol) and beta3-agonists (BRL 37344 and CL 316243), or to forskolin and 8-bromo cAMP. CGP 20712A (beta1-antagonist) efficiently inhibited lipolysis by norepinephrine, isoproterenol, and dobutamine, but did not affect lipolysis by the beta2- and beta3-agonists. ICI 118551 (beta2-antagonist) had no significant effect on lipolysis by the beta-agonists examined. CGP 20712A abolished the lipolysis-attenuating effect of PMA, but ICI 118551 did not. The protein kinase C (PKC) inhibitors, GF 109203X or Gö 6976, suppressed the effect of PMA. Pretreatment of adipocytes with PMA for 6 h caused downregulation of conventional and novel PKCs in association with a decrease in the lipolysis-attenuating effect of PMA. These results indicate that conventional and novel PKCs attenuate lipolysis mediated by beta-adrenergic receptors, probably through inhibition of the beta1-adrenergic receptor system.

Adipocytes↗
PubMed2006

Soluble adhesion molecules and C-reactive protein in the progression of silent cerebral infarction in patients with type 2 diabetes mellitus.

The purpose of this study was to investigate the association between the progression of silent cerebral infarction (SCI) and levels of soluble adhesion molecules and high-sensitivity C-reactive protein (hs-CRP) in type 2 diabetic patients. One hundred twenty middle-aged and elderly diabetic patients without histories of vascular events were followed up for a period of 3 years. We measured levels of soluble intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1, E-selectin, and hs-CRP and assessed brain ischemic lesions by magnetic resonance imaging at baseline and 3 years later. Silent cerebral infarction was observed in 13% of the patients at baseline, and these patients were significantly older and had significantly higher blood pressure than those without SCI. Thirty-two patients had newly diagnosed SCI after 3 years. There were no significant differences in factors such as age, blood pressure, and diabetic control between patients without SCI and those in whom it was newly diagnosed. However, only sICAM-1 levels, but not the other soluble adhesion molecules or hs-CRP, were associated with the progression of SCI, and this relationship remains after adjustment for risk factors. On the other hand, higher levels of sICAM-1 and hs-CRP at baseline were observed in 7 patients who were excluded from the present study because of the onset of symptomatic cerebral infarction during follow-up. Our present study suggests that sICAM-1 levels may be a potential marker for SCI, which may lead to future stroke and vascular dementia, and that this marker could be useful in monitoring disease progression and as a surrogate marker in treatment studies.

Aged↗
PubMed2006

Effects of basic fibroblast growth factor on experimental diabetic neuropathy in rats.

Basic fibroblast growth factor (bFGF) stimulates angiogenesis and induces neural cell regeneration. We investigated the effects of bFGF on diabetic neuropathy in streptozotocin-induced diabetic rats. Diabetic rats were treated with human recombinant bFGF as follows: 1) intravenous administration, 2) intramuscular injection into thigh and soleus muscles with cross-linked gelatin hydrogel (CGH), and 3) intramuscular injection with saline. Ten or 30 days later, the motor nerve conduction velocity (MNCV) of the sciatic-tibial and caudal nerves, sensitivity to mechanical stimuli, sciatic nerve blood flow (SNBF), and retinal blood flow (RBF) were measured. Delayed MNCV in the sciatic-tibial and caudal nerves, hypoalgesia, and reduced SNBF in diabetic rats were all ameliorated by intravenous administration of bFGF after 10, but not 30, days. Intramuscular injection of bFGF with CGH also improved sciatic-tibial MNCV, hypoalgesia, and SNBF after 10 and 30 days, but caudal MNCV was not improved. However, intramuscular injection of bFGF with saline had no significant effects. bFGF did not significantly alter RBF in either normal or diabetic rats. These observations suggest that bFGF could have therapeutic value for diabetic neuropathy and that CGH could play important roles as a carrier of bFGF.

Angiogenesis Inducing Agents↗
PubMed2005

Therapeutic neovascularization using cord blood-derived endothelial progenitor cells for diabetic neuropathy.

Diabetic neuropathy is based on the impairment of nerve blood flow and the metabolic disorder. Although the vasodilating agents and anticoagulants improve nerve function and symptoms in diabetic neuropathy, more effective treatments are needed. Because endothelial progenitor cells (EPCs) have been identified in adult human peripheral blood, many studies have shown that transplantation of EPCs improves circulation to ischemic tissues. In this study, we have demonstrated that therapeutic neovascularization using human umbilical cord blood-derived EPCs reversed diabetic neuropathy. EPCs were isolated and expanded on day 7 of culture from cord blood mononuclear cells. Unilateral intramuscular injection of EPCs into hindlimb skeletal muscles significantly ameliorated impaired sciatic motor nerve conduction velocity and sciatic nerve blood flow in the EPC-injected side of streptozotocin-induced diabetic nude rats compared with the saline-injected side of diabetic nude rats. Histological study revealed an increased number of microvessels in hindlimb skeletal muscles in the EPC-injected side of diabetic rats. These findings suggest that transplantation of EPCs from cord blood may be a useful treatment for diabetic neuropathy.

Animals↗
PubMed2004

Augmentation of lipolysis in adipocytes from fed rats, but not from starved rats, by inhibition of rolipram-sensitive phosphodiesterase 4.

The sensitivity of adipocytes to lipolytic agents is increased after starvation. In this study, we found that LY294002, an inhibitor of phosphatidylinositol-3 kinase (PI3K), in the concentration of more than 50 microM potentiates lipolysis induced by adenosine deaminase in adipocytes from fed rats (f-adipocytes), but not from starved rats (s-adipocytes). It also enhanced the sensitivity to lipolytic action of isoproterenol in f-adipocytes much more than s-adipocytes. The target of LY294002 may be an anti-lipolytic regulator expressed in response to food intake. Since another PI3K inhibitor, wortmannin, or a phosphodiesterase 3 (PDE3) inhibitor, cilostamide, failed to cause any specific effect to f-adipocytes, the PI3K-PDE3B pathway cannot be a target of LY294002. We found that LY294002 inhibits efficiently the cytoplasmic PDE activity of adipocytes. Rolipram, a specific inhibitor of PDE4, also inhibited the cytoplasmic PDE and caused a preferential increase of lipolysis in f-adipocytes. LY294002 blunted the actions of rolipram on lipolysis and the PDE activity. LY294002 accelerated protein kinase A activation. These data suggest that the rolipram-sensitive PDE4 is an anti-lipolytic enzyme expressed according to food intake. LY294002 may potentiate lipolysis through inhibition of the PDE4.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2004

Suppression of 3-deoxyglucosone and heparin-binding epidermal growth factor-like growth factor mRNA expression by an aldose reductase inhibitor in rat vascular smooth muscle cells.

Reactive carbonyl compounds and oxidative stress have been recently shown to up-regulate the expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent mitogen for vascular smooth muscle cells (SMCs) produced by SMC themselves. Because the polyol pathway has been reported to influence the formation of carbonyl compounds and the oxidative stress in various cells, we conducted this study to investigate whether the polyol pathway affects HB-EGF expression along with the generation of carbonyl compounds and the oxidative stress in SMCs. We found that, compared with those cultured with 5.5mM glucose, SMCs cultured with 40 mM glucose showed the accelerated thymidine incorporation, elevated levels of intracellular sorbitol, 3-deoxyglucosone (3-DG), advanced glycation end products (AGEs), and thiobarbituric acid-reactive substances (TBARS) along with the enhanced expression of HB-EGF mRNA. An aldose reductase inhibitor (ARI), SNK-860, significantly inhibited all of these abnormalities, while aminoguanidine suppressed 3-DG levels and HB-EGF mRNA expression independent of sorbitol levels. The results suggest that the polyol pathway may play a substantial role in SMC hyperplasia under hyperglycemic condition in part by affecting HB-EGF mRNA expression via the production of carbonyl compounds and oxidative stress.

Aldehyde Reductase↗
PubMed2004

Clinical potential of aldose reductase inhibitors in diabetic neuropathy.

A number of aldose reductase inhibitors (ARIs) have been developed over the past few decades with the expectation of therapeutic effects for diabetic complications. Neuropathy is the complication that has been most intensively studied as a potential target for ARIs. Most ARIs have shown satisfactory effects in animal models. However, the clinical potential of ARIs in diabetic patients has been controversial due to the lack of conclusive evidence. The safety of this category of drugs is also uncertain. This article summarizes the results of clinical trials of ARIs for patients with diabetic neuropathy that have been performed to date. The efficacy and toxicity of each ARI will be briefly assessed by the clinical data. The theoretical background along with major issues in the evaluation of drug efficacy will also be discussed. Overall the observed efficacy varied among the compounds. A few ARIs showed favorable effects in multiple endpoints in the majority of trials, while the results from many ARIs seemed ambivalent. One drug barely exhibited positive effects on any endpoint. This discrepancy may be attributable at least in part to the different degree of inhibition of the polyol pathway in nerve tissues, which is determined not only by the pharmacokinetic properties of the drug but also by its penetration into nerve tissues. In addition to the uncertain potential of each ARI, the issues of design and analytical methods used for clinical trials may underlie the ambivalent outcomes. The power of analysis and the duration of trials were apparently inadequate in a large number of the studies. Various indices selected as endpoints are not necessarily sensitive or reproducible. Studies of longer duration, large-scale trials, better methods to assess neuropathy, and the selection of patients with a homogenous background would provide more conclusive evidence. The risk of serious adverse reactions, for example, hypersensitivity reactions and hepatic damage, has led to some ARIs being withdrawn from the market or from further development. These adverse effects, however, do not appear to result from the inhibition of aldose reductase activity per se but from specific reactions to each compound. In conclusion, sufficient inhibition of the nerve aldose reductase activity seems likely to prevent or ameliorate diabetic neuropathy, and further development of more potent and safe ARIs is necessary before extensive clinical application.

Aldehyde Reductase↗
PubMed2003

Magnetic resonance imaging measurements of extraocular muscle path shift and posterior eyeball prolapse from the muscle cone in acquired esotropia with high myopia.

PURPOSE: To investigate extraocular muscle (EOM) path shift and prolapse of posterior eyeball from muscle cone in acquired esotropia with high myopia (AEHM), using magnetic resonance imaging. DESIGN: A case-control study. METHODS: There were 16 eyes with AEHM, 11 with high myopia (HM), 12 with moderate myopia (MM), and 11 control eyes. Extraocular muscle shift was evaluated by measuring angles formed by the line connecting orbital centroids and the line connecting each orbital centroid and each EOM centroid. The ratio of the prolapse in the posterior eyeball from the muscle cone was also measured. RESULTS: Both inferior shift of lateral rectus (LR) and nasal shift of superior rectus (SR) muscle were observed in the AEHM group, compared with HM, MM, and control groups. Neither shifted significantly in the HM group compared with control group. The prolapse ratio in AEHM group was higher than in the HM, MM, and control groups. Greater EOM shifts and eyeball prolapse were observed when the AEHM was more severe, as in esotropia fixus. CONCLUSIONS: In AEHM, a prolapsing eyeball shifts LR inferiorly and SR nasally; these findings were not observed in high myopia with neither ocular deviation nor restriction. These shifts reduce abduction and supraduction and increase infraduction and adduction in AEHM. The shifts would be predicted to create a hypoesodeviation, which is a common finding in AEHM. Both EOM shifts and superotemporal eyeball prolapse tend to be greater in esotropia fixus.

Case-Control Studies↗
PubMed2003

The role of polyol pathway in glucose-induced apoptosis of cultured retinal pericytes.

The pathogenesis of pericyte loss, an initial deficit in the early stage of diabetic retinopathy, remains unclear. Recent studies have suggested that polyol pathway hyperactivity and apoptosis may be involved in pericyte loss. The mechanisms of the glucose-induced apoptosis in retinal pericytes were investigated to evaluate the pathogenesis of diabetic retinopathy. Under the 20 mM glucose condition, intracellular calcium concentrations and caspase-3 activities were significantly increased, and reduced glutathione (GSH) contents were significantly decreased compared with those under the 5.5 mM glucose condition. These abnormalities were all significantly prevented by an aldose reductase inhibitor, SNK-860. Glucose-induced apoptosis was partially but significantly prevented by SNK-860, an inhibitor of calcium-dependent cysteine protease, calpain, or GSH supplementation, and completely normalized by a caspase-3 inhibitor. These observations suggest that glucose-induced apoptosis in retinal pericytes, as one of the pathogenic factors of diabetic retinopathy, would be mediated through an aldose reductase-sensitive pathway including calcium-calpain cascade and increased oxidative stress, and that caspase-3 would be located furthest downstream of these apoptotic signals.

Aldehyde Reductase↗
PubMed2003

Imaging of (13)C-labeled glucose and sorbitol in bovine lens by (1)H-detected (13)C nuclear magnetic resonance spectroscopy.

Bovine lenses were incubated in a solution containing [1-(13)C]glucose (50 mM) for 1, 2 and 4 days. Spectroscopic images of [1-(13)C]glucose and [1-(13)C]sorbitol were constructed using (1)H-detected gradient-enhanced heteronuclear multiple-quantum coherence (GE-HMQC) in a 2.0-tesla magnetic field. Accumulations of [1-(13)C]glucose and [1-(13)C]sorbitol were mainly observed at the periphery of the lens. Their distributions corresponded to the cortex. (1)H-detected (13)C nuclear magnetic resonance (NMR) spectroscopic imaging by GE-HMQC successfully demonstrated the distribution of [1-(13)C]glucose and [1-(13)C]sorbitol at the periphery of bovine lenses.

Animals↗
PubMed2003

[Localization of glucose and sorbitol in incubated bovine lenses using chemical shift imaging].

PURPOSE: To use chemical shift imaging (CSI) to measure the metabolic changes in glucose metabolites in bovine lenses incubated in tissue culture medium 199(TCM 199) with a high concentration of glucose and to evaluate the viability of this method. METHODS: We detected an accumulation of 13C-labeled glucose and sorbitol in the bovine lenses incubated in TCM 199 containing 50 mM glucose-1-13C for 1, 2, 4, or 6 days using a 2 T CSI Omega system. 1H-13C gradient-selected heteronuclear multiple-quantum coherence (GH-HMQC) in nuclear magnetic resonance (NMR), an indirect method of detecting nuclei in low sensitivity by 1H NMR, was used to observe 13C-enriched metabolites in the bovine lens in vivo. RESULTS: We found an accumulation of 13C-labeled glucose and sorbitol using the 2 T CSI Omega system. The level of glucose increased rapidly in the posterior segment of the lens as well as the anterior segment at one day after the beginning of incubation. Then it diminished gradually, and could no longer be detected on the 6th day after the start of incubation possibly because of the breakdown of the cell membrane. The levels of sorbitol increased in the anterior area and the equator of the lens one day after the beginning of incubation, and remained unchanged for 6 days. CONCLUSION: We encountered many problems especially with the imaging resolution (consequently the time for measurement was prolonged), but this approach may be useful for non-invasive monitoring of 13C-labeled compounds. We believe this method will be especially useful for detecting various metabolites in vivo.

Animals↗
PubMed2002

Expression of protein gene product 9.5 in the anterior lens epithelial cells of atopic cataracts.

PURPOSE: To investigate the mechanisms of atopic cataract by immunohistochemically observing protein gene product 9.5 in lens epithelial cells (LECs) of atopic cataracts. SETTING: Departments of Ophthalmology and Anatomy, Shiga University of Medical Science, Shiga, Japan. METHODS: Specimens of anterior capsule obtained from 6 patients with atopic cataract and 8 patients with senile cataract were stained immunohistochemically and examined by light, electron, and confocal microscopy. RESULTS: In the LECs of the atopic cataracts, the arrangement and cell shape were varied. Immunohistochemistry for protein gene product 9.5 demonstrated selective localization, unlike with senile cataracts. This was especially prevalent in the spindle-shaped cells around the central opaque lesion. Protein gene product 9.5 positive cells overlapped with major basic protein positive cells in the atopic cataracts. CONCLUSIONS: The results indicate that the properties of LECs of atopic cataracts are different from those of senile cataracts. Protein gene product 9.5 and major basic protein seem to be concentrated in atopic cataracts.

Adult↗
PubMed2002

Magnetic resonance imaging studies of the volume of the rabbit eye with intravenous mannitol.

PURPOSE: Changes in the volume of rabbit eyes after intravenous mannitol injection were studied non-invasively using 3D-magnetic resonance imaging (MRI). METHODS: Images of eight rabbit eyes were obtained using a 3D-gradient echo technique before and at 30, 60 and 90 minutes after mannitol injection at 4 g/kg. To evaluate the volume, the cross-sectional area of the eye in the central 5 slices was traced and totaled. The intraocular pressure (IOP) of five rabbits was measured before and after administration. RESULTS: The total area of the eyeball decreased significantly at 60 minutes. The total area of the anterior chamber, iris plus ciliary body decreased rapidly and then recovered. The decrease in the vitreous and the IOP was consistently significant during the 90-minute observation period. CONCLUSIONS: Consecutive MRIs enabled us to measure the changes in eye volume of the same rabbit before and after mannitol injection in a non-invasive manner.

Animals↗