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Biomedical subjects

M Kinoshita

Publications and source records attributed to M Kinoshita.

At least 37 records · Page 2Linked to original sources
PubMed2002

Fukuyama-type congenital muscular dystrophy: a case report in the Japanese population living in Brazil.

INTRODUCTION: We present herein clinical, histological and magnetic resonance imaging (MRI) findings in a patient with Fukuyama-type congenital muscular dystrophy (FCMD). He is the first case report in the Japanese population living in Brazil. CASE REPORT: The child presented with neonatal hypotonia, delayed motor abilities and speech, seizures, cerebral and cerebellar gyrus abnormalities with signal intensity change in the white matter by MRI, high serum level of creatinephosphokinase (CK), and dystrophic skeletal muscle with normal merosin, alpha-sarcoglycan and dystrophin expression. The fukutin gene study showed one founder 3-kb retrotransposal insertion in the 3'-non-coding region, and in the other allele no mutation was detected after screening all exons and flanking introns by sequencing. DISCUSSION: This case report emphasizes the importance to consider FCMD in Japanese people living in other countries.

Brain↗
PubMed2002

The effect of sildenafil on electrostimulation-induced erection in the rat model.

This study was conducted to show the effect of sildenafil on electrostimulation-induced erection in the rat model. Fifteen 12-week-old male Wistar Kyoto rats were used. The intracavernous pressure and arterial blood pressure were simultaneously monitored through electric cavernous nerve stimulation before and after the administration of sildenafil (2 mg/kg). Statistical analysis was performed on maximal intracavernous pressure (MIP), mean arterial blood pressure (MAP), the MIP/MAP and detumescence time. MAP decreased significantly by about 20 mmHg after sildenafil administration. The MIP/MAP increased significantly after sildenafil administration. The effect of sildenafil on the MIP/MAP was marked especially at lower (2-3 Hz) frequencies. The detumescence time significantly increased after sildenafil administration. We have shown that sildenafil is effective for enhancing erection at lower frequencies and prolonging penile erection in rats. After the administration of sildenafil, penile erection would be induced by weak stimuli that will not cause penile erection under normal conditions.

Animals↗
PubMed2002

Can coronary flow velocity reserve determined by transthoracic Doppler echocardiography predict the recovery of regional left ventricular function in patients with acute myocardial infarction?

OBJECTIVE: To determine whether the early assessment of coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography (TTDE) can predict myocardial viability after revascularisation in patients with acute myocardial infarction. METHODS: 29 patients with anterior acute myocardial infarction who were successfully treated by coronary angioplasty were studied. TTDE was used to record coronary flow velocities in the distal left anterior descending artery at rest and during hyperaemia induced by intravenous infusion of adenosine triphosphate. CFVR was calculated immediately and 24 hours after revascularisation and at discharge. Regional wall motion was analysed to calculate the anterior wall motion score index (A-WMSI) by two dimensional echocardiography before revascularisation and at discharge. RESULTS: CFVR immediately and 24 hours after revascularisation correlated significantly with A-WMSI at discharge (r = -0.58, p < 0.001 and r = -0.80, p < 0.0001, respectively). CFVR 24 hours after revascularisation was a better predictor of recovery of regional left ventricular function than CFVR immediately after revascularisation. The optimal cut off ratio for predicting viable myocardium was 1.5 for CFVR 24 hours after revascularisation (sensitivity = 94%, specificity = 91%). CONCLUSIONS: CFVR by TTDE was useful for predicting the recovery of left ventricular function after revascularisation in patients with acute myocardial infarction

Analysis of Variance↗
PubMed2001

FK506 suppressed the inflammatory change of EAM in SJL/J mice.

Experimental autoimmune myositis (EAM) is a good model of human inflammatory myopathy. We induced EAM in SJL/J mice by injection with myosin and treated inflammatory changes with FK506. The mice developed inflammatory changes after the fifth myosin injection. After treatment with FK506, inflammation was suppressed and central nuclei of the muscle fibers increased. These findings indicate that FK506 is effective in the treatment of EAM. The data suggests that FK506 inhibits interaction with calcineurin. Intercellular adhesion molecule-1 (ICAM-1) positive cells were present in the inflammatory and non-inflammatory areas of EAM. The FK506-treated group stained more weakly for ICAM-1 than the untreated EAM group.

Animals↗
PubMed2001

Specific distribution of sialic acids in animal tissues as examined by LC-ESI-MS after derivatization with 1,2-diamino-4,5-methylenedioxybenzene.

Simultaneous analysis of sialic acids has been a challenging target, because sialic acids having N- or O-acetyl, glycolyl, and sulfonic acid ester groups are labile during their release from carbohydrate chains and analytical procedures. In the present paper, we propose a method using high-performance liquid chromatography coupled with eletrospray ionization mass spectrometry (HPLC-ESI-MS). The method was evaluated by applying to the analysis of sialic acids in various tissues, especially digestive organs in mice and rats. The method was based on the in situ precolumn derivatization of sialic acids after releasing them by hydrolysis. The sialic acids were derivatized with 1,2-diamino-4,5-methylenedioxybenzene to form highly fluorescent quinoxaline derivatives. By using two different hydrolysis conditions (i.e., with 2 M acetic acid and with 0.1 M hydrochloric acid), both total sialic acids and sialic acid distributions were easily determined. We found that sialic acids showed characteristic distributions in the tissues of mice and rats. Further, HPLC-ESI-MS revealed that all the tissues examined in mice and rats commonly contained highly acetylated sialic acids and 8-O-sulfated N-acetylneuraminic acid.

Animals↗
PubMed2001

Relationship between transcardiac extraction of aldosterone and left ventricular remodeling in patients with first acute myocardial infarction: extracting aldosterone through the heart promotes ventricular remodeling after acute myocardial infarction.

OBJECTIVES: The purpose of this study was to evaluate whether plasma aldosterone (ALD) is extracted or produced through the heart in patients with acute myocardial infarction (AMI) and to determine the relationship between transcardiac extraction of plasma ALD and left ventricular (LV) remodeling. BACKGROUND: Although we demonstrated that circulating ALD was extracted through the failing heart and that transcardiac extraction of ALD correlated with LV end-diastolic volume index (LVEDVI) in patients with congestive heart failure, the existence and increase of ALD synthase in the hearts of infarct rats were reported, suggesting cardiac production of ALD in patients with AMI. METHODS: We measured plasma ALD in the aortic root (Ao) and coronary sinus (CS) in 57 consecutive patients who received successful revascularization and enalapril, with first AMI at acute phase and after one month. We also measured plasma procollagen type III aminoterminal peptide (PIIINP) in the CS. RESULTS: Plasma ALD was significantly lower in the CS than it was in the Ao at the acute phase (84.7 +/- 6.3 pg/ml vs. 105.5 +/- 8.0 pg/ml, p < 0.0001). Significant positive correlations exist between the transcardiac gradient of ALD at the acute phase and the LVEDVI at one month. Moreover, the transcardiac gradient of plasma ALD at the acute phase has a significant correlation with plasma PIIINP, a biochemical marker of fibrosis, after one month. Stepwise multivariate analysis showed that transcardiac extraction of plasma ALD at the acute phase had an independent and significant positive relationship with a large LVEDVI after one month. CONCLUSIONS: These results indicate that plasma ALD is extracted through the heart in patients with AMI at the acute phase and that the extracted ALD plays an important role in modulating post-infarct LV remodeling.

Acute Disease↗
PubMed2001

Relationship between plasma level of cardiotrophin-1 and left ventricular mass index in patients with dilated cardiomyopathy.

OBJECTIVES: The study evaluated the relationship between plasma cardiotrophin-1 (CT-1) concentration and left ventricular (LV) mass in dilated cardiomyopathy (DCM) patients with congestive heart failure (CHF). BACKGROUND: Cardiotrophin-1 is a newly identified member of the interleukin-6 (IL-6) family of cytokines and one of the endogenous ligands for gp130 signaling pathways in the heart, and it has potent hypertrophic and survival effects on cardiac myocytes. However, the clinical significance of CT-1 is poorly understood. METHODS: We measured the plasma CT-1 level in 51 consecutive patients with DCM. Patients were classified into two groups: small LV mass index group and large LV mass index group, based on the median level of LV mass index. RESULTS: The plasma CT-1 level was increased in DCM patients with the severity of CHF and was significantly higher in the large LV mass group than in the small LV mass group, despite the absence of a difference in LV ejection fraction between the two groups. In addition, there was a significant positive correlation between the plasma CT-1 level and the LV mass index (r = 0.627, p < 0.0001). According to stepwise multivariate analyses among hemodynamic and neurohumoral factors, a high plasma CT-1 level showed an independent and significant positive relationship with a large LV mass index in patients with DCM. CONCLUSIONS: These results indicate that the plasma CT-1 level is increased in patients with DCM and is significantly correlated with the LV mass index, suggesting that CT-1 plays an important role in structural LV remodeling in patients with DCM.

Adolescent↗
PubMed2001

Fluorescence polarization: analysis of carbohydrate-protein interaction.

Fluorescence polarization has been widely used for the studies on the molecular motion in solution and has been applied to immunoassays for proteins, therapeutic drug monitoring in clinical pharmacy, and assays for environmentally toxic compounds. Because fluorescence polarization is most readily applicable to the kinetic analysis of the binding reaction between a substance having small molecular mass and a receptor molecule, this method is easily applied to the analysis of carbohydrate-lectin binding. In this tutorial Thematic Review, we briefly introduce the principles of fluorescence polarization and some applications of fluorescence polarization technique to glycobiology.

Aspergillus oryzae↗
PubMed2001

Endothelin-1 promotes vascular structural remodeling during the progression of heart failure prevention of vascular remodeling using a specific endothelin-converting enzyme inhibitor.

To evaluate the effects of endothelin (ET)-converting enzyme (ECE) inhibitor on vascular remodeling in dogs with congestive heart failure (CHF), we chronically administered an ECE inhibitor, FR901533 (FR, iv. 0.3mg/kg/hr, n=6), to dogs with CHF induced by rapid ventricular pacing. Vehicle CHF dogs were given saline (n=7). In the vehicle CHF group after 3 weeks of pacing, the ET system was activated in the plasma and vasculature (3 and 5 times higher than normal, respectively). Inward remodeling occurred in the femoral artery; medial thickness (MT, 225+/-5 vs 193+/-4 microm, P<0.05) and deposition of collagen (DC, 22+/-2 vs 17+/-1%, P<0.01) significantly increased, while lumen diameter (LD, 1173+/-39 vs 1481+/-44 microm, P<0.05) decreased in the femoral artery with CHF compared with the normal femoral artery. There were significant correlations between the number of ET-1 positive cells and MT, DC, LD and systemic vascular resistance. FR significantly suppressed the changes in these vascular parameters compared with the changes in the vehicle CHF group despite the lack of an effect on blood pressure, and moreover FR caused decreases in ET-1 levels in both the plasma and femoral artery (reduced to 43% and 54%, respectively, of the levels in the vehicle CHF group, P<0.05). In conclusion, ET-1 plays a critical role in the structural deterioration of the vasculature during the progression of CHF, and ECE inhibitors can prevent the development of vascular remodeling.

Animals↗
PubMed2001

The see-through medaka: a fish model that is transparent throughout life.

The see-through medaka is a vertebrate model with a transparent body in the adult stage, as well as during the embryonic stages, that was generated from a small laboratory fish, medaka (Oryzias latipes). In this fish model, most of the pigments are genetically removed from the entire body by a combination of recessive alleles at four loci. The main internal organs, namely, heart, spleen, blood vessels, liver, gut, gonads, kidney, brain, spinal cord, lens, air bladder, and gills, in living adult fish are visible to the naked eye or with a simple stereoscopic microscope. This fish is healthy and fertile. A transgenic see-through medaka was produced by using the green fluorescent protein (GFP) gene fused to the regulatory regions of the medaka vasa gene, in which germ cell-specific expression of GFP was visualized. The fluorescent tag also efficiently improved visibility of gonadal tissues. The process of oocyte maturation in the ovary was monitored by repeated observations from the outside of the body during one spawning cycle in the same living females of the transgenic see-through stock. The see-through medaka will provide an opportunity for noninvasive studies of morphological and molecular events that occur in internal organs in the later stages of life.

Animals↗
PubMed2001

Stimulus time-locked responses of motoneurons during forelimb fictive locomotion evoked by repetitive stimulation of the lateral funiculus.

In cat forelimb fictive locomotion evoked by repetitive stimulation of the upper cervical lateral funiculus, locomotor discharges consisted of activities time-locked to each stimulus, which were rhythmically modulated. The stimulus time-locked activities were investigated by intracellular recording from motoneurons. In both elbow flexor and extensor motoneurons, there observed stimulus time-locked disynaptic EPSPs, trisynaptic IPSPs and polysynaptic EPSPs, all of which were rhythmically modulated with specific patterns. The disynaptic EPSPs of flexor motoneurons were facilitated in the flexor phase of locomotion, whereas those of extensor motoneurons were facilitated from the flexor phase to the flexor-to-extensor transition phase. Modulation depth was larger in flexor motoneurons. Trisynaptic IPSPs changed in amplitude in parallel with the disynaptic EPSPs of the antagonistic motoneurons. Late, polysynaptic EPSPs of both flexor and extensor motoneurons increased in amplitude along with corresponding nerve discharges. After lesions of the lateral funiculus at C6/C7, both the disynaptic EPSPs and trisynaptic IPSPs were abolished in the motoneurons located caudally to the lesions. However, only trisynaptic IPSPs were lost in the rostrally located motoneurons. Furthermore, the lesions disclosed that extensor motoneurons received another kind of stimulus time-locked EPSPs, trisynaptic EPSPs, which were transmitted through the ventral part of the spinal cord, and rhythmically facilitated in the extensor phase. Stimulus time-locked PSPs observed in this study may at least in part be evoked by last-order interneurons of the central pattern generator, which may be reciprocally organized.

Action Potentials↗
PubMed2001

Identification of human endomucin-1 and -2 as membrane-bound O-sialoglycoproteins with anti-adhesive activity.

Using a signal sequence trap method and database search, we identified a series of human cDNAs encoding two structurally related type I membrane proteins of approximately 25 kDa with multiple glycosylation motifs. These genes, termed endomucin-1/-2, are expressed in several human tissues including heart, kidney, and lung. Exogenously expressed human endomucin-1/-2 proteins were modified into 80-120 kDa glycoproteins, which were susceptible to O-sialoglycoprotein endopeptidase digestion. Transient overexpression of endomucin-1/-2 reduced the number of adhesion plaques and reduced cell attachment to the substrate. This phenotype was suppressed by laminin or the protein kinase inhibitor staurosporine. Our findings suggest that human endomucin-1/-2 negatively regulate cell adhesion to the extracellular matrix.

Amino Acid Sequence↗
PubMed2001

Relationship between tumor necrosis factor-alpha production and oxidative stress in the failing hearts of patients with dilated cardiomyopathy.

OBJECTIVES: This study evaluated oxidative stress in the failing ventricle in patients with dilated cardiomyopathy (DCM). BACKGROUND: Oxidative stress appears to increase in the failing myocardium and may contribute to ventricular dysfunction in patients with DCM. Tumor necrosis factor-alpha (TNF-alpha), which is expressed in the failing heart, may stimulate oxidative stress. METHODS: We measured plasma oxidized low density lipoprotein (oxLDL) by sandwich enzyme-linked immunosorbent assay using specific antibodies against oxLDL in the aortic root (AO) and the coronary sinus (CS) in control subjects (n = 8) and in 22 patients with DCM and mild congestive heart failure. We also measured the plasma levels of TNF-alpha and angiotensin II. RESULTS: There was no difference in oxLDL between the AO and CS in control subjects. In contrast, plasma oxLDL was significantly higher in the CS than the AO in patients with DCM, suggesting that the transcardiac gradient ofoxLDL reflects oxidative stress in the failing heart in these patients. Plasma TNF-alpha levels were significantly higher in the CS than the AO with a significant positive correlation of the transcardiac gradient of TNF-alpha and the transcardiac gradient of oxLDL. Moreover, a significant negative correlation existed between the transcardiac gradient of oxLDL and left ventricular ejection fraction. The transcardiac gradient of plasma oxLDL was significantly lower in 6 patients who received carvedilol than in 16 patients who did not receive carvedilol. CONCLUSIONS: These findings indicate that the transcardiac gradient of oxLDL may be a marker of oxidative stress in the heart and that left ventricular dysfunction may be partly due to the oxidative stress in patients with DCM. In addition, TNF-alpha may stimulate oxidative stress in the failing heart in patients with DCM.

Adolescent↗
PubMed2001

Binding of G alpha(o) N terminus is responsible for the voltage-resistant inhibition of alpha(1A) (P/Q-type, Ca(v)2.1) Ca(2+) channels.

G-protein-mediated inhibition of presynaptic voltage-dependent Ca(2+) channels is comprised of voltage-dependent and -resistant components. The former is caused by a direct interaction of Ca(2+) channel alpha(1) subunits with G beta gamma, whereas the latter has not been characterized well. Here, we show that the N terminus of G alpha(o) is critical for the interaction with the C terminus of the alpha(1A) channel subunit, and that the binding induces the voltage-resistant inhibition. An alpha(1A) C-terminal peptide, an antiserum raised against G alpha(o) N terminus, and a G alpha(o) N-terminal peptide all attenuated the voltage-resistant inhibition of alpha(1A) currents. Furthermore, the N terminus of G alpha(o) bound to the C terminus of alpha(1A) in vitro, which was prevented either by the alpha(1A) channel C-terminal or G alpha(o) N-terminal peptide. Although the C-terminal domain of the alpha(1B) channel showed similar ability in the binding with G alpha(o) N terminus, the above mentioned treatments were ineffective in the alpha(1B) channel current. These findings demonstrate that the voltage-resistant inhibition of the P/Q-type, alpha(1A) channel is caused by the interaction between the C-terminal domain of Ca(2+) channel alpha(1A) subunit and the N-terminal region of G alpha(o).

Amino Acid Sequence↗
PubMed2001

Intravenous atrial natriuretic peptide prevents left ventricular remodeling in patients with first anterior acute myocardial infarction.

OBJECTIVES: The study evaluates the effect of atrial natriuretic peptide (ANP) compared with nitroglycerin (GTN) on left ventricular (LV) remodeling after first anterior acute myocardial infarction (AMI). BACKGROUND: Compared with GTN, ANP suppresses the renin-angiotensin-aldosterone system and endothelin-1 (ET-1), which stimulate LV remodeling. METHODS: Sixty patients with a first anterior AMI were randomly divided into the ANP (n = 30) or GTN (n = 30) groups after direct percutaneous transluminal coronary angioplasty. We evaluated LV ejection fraction (LVEF), end-diastolic volume index (LVEDVI) and end-systolic volume index (LVESVI) at the acute phase and after one month. We also measured neurohumoral factors during study drug infusion. RESULTS: There was no difference in the baseline characteristics or LVEF (46.9+/-1.0 vs. 46.8+/-1.3%) between the two groups. Although there was no difference in hemodynamics during the infusion periods, the LVEF was significantly improved after one month compared with the baseline value in both groups, but it was improved more in the ANP group than in the GTN group (54.6+/-1.1%, 50.8+/-1.3%, p < 0.05). Left ventricular enlargement was prevented in the ANP group (LVEDVI, 85.8+/-3.1 ml/m2 to 87.3+/-2.7 ml/m2; p = ns, LVESVI, 45.6+/-1.8 ml/m2 to 41.0+/-2.1 ml/m2, p < 0.05) but not in the GTN group (LVEDVI, 86.2+/-4.1 to 100.2+/-3.7, p < 0.01; LVESVI, 46.3+/-2.8 ml/m2 to 51.1+/-3.0 ml/m2, p = ns). During the infusion, ANP suppressed plasma levels of aldosterone, angiotensin II and ET-1 compared with GTN. CONCLUSIONS: These findings indicate that in patients with a first anterior AMI, an ANP infusion can prevent LV remodeling better than can GTN, and effectively suppresses aldosterone, angiotensin II and ET-1.

Atrial Natriuretic Factor↗
PubMed2001

Capillary electrophoresis of sialic acid-containing glycoprotein. Effect of the heterogeneity of carbohydrate chains on glycoform separation using an alpha1-acid glycoprotein as a model.

alpha1-Acid glycoprotein (AGP) showed multiple peaks on separation using capillary electrophoresis in a chemically modified capillary with dimethylpolysiloxane at slightly acidic conditions. We analyzed glycoforms of AGP species after separation by ion-exchange chromatography, Con A affinity chromatography, and Cu(II)-chelating affinity chromatography. The AGP species thus obtained were digested with N-glycosidase F, and the released carbohydrate chains were analyzed by high-performance liquid chromatography after labeling with 3-aminobenzoic acid. The results afforded basic information on the contribution of carbohydrate chains to the separation mechanism of glycoforms of AGP by capillary electrophoresis. In addition, we describe an easy method for AGP analysis in serum samples using the electrokinetic injection.

Carbohydrate Sequence↗