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Biomedical subjects

M Matsuzaki

Publications and source records attributed to M Matsuzaki.

At least 37 records · Page 2Linked to original sources

Eicosapentaenoic acid (EPA) induces Ca(2+)-independent activation and translocation of endothelial nitric oxide synthase and endothelium-dependent vasorelaxation.

Eicosapentaenoic acid (EPA), but not its metabolites (docosapentaenoic acid and docosahexaenoic acid), stimulated nitric oxide (NO) production in endothelial cells in situ and induced endothelium-dependent relaxation of bovine coronary arteries precontracted with U46619. EPA induced a greater production of NO, but a much smaller and more transient elevation of intracellular Ca(2+) concentration ([Ca(2+)]i), than did a Ca(2+) ionophore (ionomycin). EPA stimulated NO production even in endothelial cells in situ loaded with a cytosolic Ca(2+) chelator 1,2-bis-o-aminophenoxythamine-N',N',N'-tetraacetic acid, which abolished the [Ca(2+)]i elevations induced by ATP and EPA. The EPA-induced vasorelaxation was inhibited by N(omega)-nitro-L-arginine methyl ester. Immunostaining analysis of endothelial NO synthase (eNOS) and caveolin-1 in cultured endothelial cells revealed eNOS to be colocalized with caveolin in the cell membrane at a resting state, while EPA stimulated the translocation of eNOS to the cytosol and its dissociation from caveolin, to an extent comparable to that of the eNOS translocation induced by a [Ca(2+)]i-elevating agonist (10 microM bradykinin). Thus, EPA induces Ca(2+)-independent activation and translocation of eNOS and endothelium-dependent vasorelaxation.

Animals↗

Autologous bone marrow implantation induced angiogenesis and improved deteriorated exercise capacity in a rat ischemic hindlimb model.

BACKGROUND: Bone marrow possesses endothelial progenitor cells that secrete several growth factors and can contribute to the formation of new capillaries. In the present study, we investigated the extent of angiogenesis induced by implantation of autologous bone marrow cells (BMCs) in a rat ischemic hindlimb model and studied whether the increased collateral vessels can improve deteriorated physical function. MATERIALS AND METHODS: Ischemic hindlimb was created by ligation of the femoral artery and its branches in Dark Agouti (DA) rats. BMCs (1 x 10(7)) were injected percutaneously at six points into the gastrocnemius muscle. To assess angiogenesis, histologic evaluation and microangiography were performed at 2 weeks postligation. Severity of the ischemic insult was evaluated by measuring blood flow in the adductor and gastrocnemius muscles using nonradioactive colored microspheres and by determining the femoral arteriovenous oxygen difference (AVDO(2)) at 2 weeks postligation. Running time on a motor-driven treadmill was used to represent exercise capacity. RESULTS: The histologic evaluation and microangiogram showed that the implanted BMCs induce angiogenesis. Blood flow to the adductor muscle on the treated side in the bone marrow cell implantation (BMI) group was significantly restored to 77.3 +/- 19.3% of that of the normally perfused limb in comparison to that in control groups (P < 0.05). AVDO(2) in the BMI group significantly decreased when compared with AVDO(2) in control groups. Rats in the BMI group ran approximately 1.5 times longer than rats in control groups at 2 and 4 weeks postligation (P < 0.01). CONCLUSIONS: Implantation of autologous BMCs induced angiogenesis and improved deteriorated exercise capacity in our rat ischemic hindlimb model.

Angiography↗

Large amounts of apicoplast nucleoid DNA and its segregation in Toxoplasma gondii.

Apicoplasts (apicomplexan plastids) are nonphotosynthetic, secondary endosymbiotic plastids that are found in most apicomplexans. Although these organelles are essential for parasite survival, their functions, activities, and structures are not well understood. We examined the apicoplast nucleoid of Toxoplasma gondii from a morphological aspect by high-resolution epifluorescence microscopy and electron microscopy. We found unexpectedly large amounts of DNA in the nucleoid and the presence of several division-related structures. Initially, we identified the organellar nucleoids by staining with the DNA-specific dye 4',6-diamidino-2-phenylindole. A single nucleoid was observed per apicoplast, and the fluorescent spot representing the nucleoid was bright and spherical in contrast to the weak and filamentous spot representing the mitochondrial nucleoid. We also measured the DNA content of each apicoplast nucleoid by a video-intensified microscope photon-counting system and determined that the genomic copy number was at least 25, a figure over four times greater than that reported previously. Moreover, several groups of apicoplasts had significantly higher genomic copy numbers. The DNA molecules were accurately divided into two daughter apicoplasts just before nuclear division. In addition, we examined nucleoid segregation and the division apparatus using electron microscopy. However, we failed to observe nucleoid structures, suggesting that the apicoplasts are predominantly composed of nucleoid material. In addition, we observed "cap" structures at the termini of dividing apicoplasts, a possible plastid-dividing ring, and a microbody-like granule around the constriction. These structures may be involved in apicoplast division.

Animals↗

Bronchiolitis obliterans organizing pneumonia (BOOP) with suspected liver graft-versus-host disease after allogeneic bone marrow transplantation.

We report on a patient with chronic myelogenous leukemia who developed bronchiolitis obliterans organizing pneumonia (BOOP) after allogeneic bone marrow transplantation (BMT). A 19-year-old Japanese male complained of dry cough and dyspnea 7 months after BMT. The chest X-ray and computed tomography revealed patchy infiltrates bilaterally. Lung function test, lung biopsy and bronchoalveolar lavage were consistent with the diagnosis of BOOP. The patient also suffered from suspected graft-versus-host disease (GVHD) of the liver, after discontinuation of cyclosporine. Furthermore, prednisolone proved effective against the BOOP and the liver dysfunction. These findings indicate that BOOP is a possible pulmonary manifestation of chronic GVHD, and that immunological mechanisms may have effected the onset of BOOP after BMT in this case.

Adult↗

Direct closure of ostium primum defect in the repair of atrioventricular septal defect.

BACKGROUND: Patch closure is generally performed for atrial septation of an atrioventricular septal defect. We recently developed a new surgical technique for repairing atrioventricular septal defects that avoids the use of any patch material for closing the atrial septal defect. We report our experience with this procedure. METHODS: Seven patients (complete type: 5, partial type: 2) underwent this new operation. The diameters of the atrial septal defects were measured by transesophageal echocardiography. The preoperative electrocardiograms were compared with those taken after the operations. RESULTS: Diameters of the atrial defects ranged from 3 to 10 mm. Electrocardiograms before and after the operations did not change. No significant atrioventricular valve regurgitation and no residual shunts were detected by postoperative echocardiography. CONCLUSIONS: This method simplifies the repair of atrioventricular septal defects. In the short-term results, no arrhythmia and no valve regurgitation was seen.

Blood Vessel Prosthesis Implantation↗

Glycerol affects vestibular evoked myogenic potentials in Meniere's disease.

OBJECTIVES: to show that abnormal vestibular evoked myogenic potentials on the sternocleidomastoid muscle (SCM) in patients with unilateral Meniere's disease are caused by endolymphatic hydrops. SUBJECTS: six normal volunteers and 17 patients with unilateral Meniere's disease were examined. METHODS: click-evoked myogenic potentials were recorded with surface electrodes over each SCM. Responses evoked by clicks recorded after oral administration of glycerol (1.3 g/kg body weight) were compared with those recorded before administration. RESULTS: the change rate of the p13-n23 amplitude was calculated. The mean+standard deviation (S.D.) of the change rate was 3.52+14.6% in normal subjects. On the unaffected side of patients the change rates were within the normal range (within the mean+/-2S.D.) in 13 patients, and three ears showed significant decrease. Only one ear showed significant increase. On the affected side, five ears showed significant increase of the amplitude while two ears showed significant decrease after oral administration of glycerol. Effects on evoked myogenic potentials were independent of those on pure tone hearing. CONCLUSION: vestibular evoked myogenic potentials in some patients with unilateral Meniere's disease were improved by oral administration of glycerol. This result suggests that abnormal vestibular evoked myogenic potentials in patients with unilateral Meniere's disease could result from endolymphatic hydrops.

Administration, Oral↗

Improvement of afterload mismatch of left atrial booster pump function with positive inotropic agent.

OBJECTIVES: The objective of this study was to examine the hypothesis that a positive inotropic agent improves left ventricular (LV) filling during left atrial (LA) contraction in the presence of markedly elevated LV filling pressure. BACKGROUND: In patients with old myocardial infarction (MI), an increase in the operational LV chamber stiffness reduces LV filling during the LA contraction, resulting from an "afterload mismatch" of the LA booster pump function. METHODS: We investigated the effect of dobutamine infusion (3 microg/kg/min) on the LA pump function in the presence of elevated LV filling pressure induced by aortic constriction (Aoc) during acute MI in 10 dogs. Transmitral flow velocity was determined by transesophageal echocardiography, LV pressure by a micromanometer and LV volume by a conductance catheter. We measured the early (E) and late (A) diastolic peak transmitral flow velocities (cm/s) and LV chamber stiffness (deltaP/deltaV: mm Hg/ml; where deltaP is developed pressure and deltaV is the absolute filling volume during LA contraction). RESULTS: When the deltaP/deltaV was increased by Aoc during MI (from 1.1 +/- 0.8 to 3.1 +/- 2.6 mm Hg/ml, p < 0.01), A decreased significantly (from 30 +/- 5 to 22 +/- 8 cm/s, p < 0.01), and the ratio of E to A increased (from 1.0 +/- 0.3 to 1.4 +/- 0.8, p < 0.05) compared with MI without Aoc, showing the pseudonormal transmitral flow pattern, the so called "LA afterload mismatch." Dobutamine under this condition significantly reduced the deltaP/deltaV (to 1.7 +/- 1.2 mm Hg/ml, p < 0.05), resulting in an increase in A (to 31 +/- 8 cm/s, p < 0.01) and a decrease in E/A (to 1.0 +/- 0.3, p < 0.05), and the transmitral flow became a prolonged relaxation pattern as in MI without Aoc in all dogs. There was an inverse correlation between the deltaP/deltaV and the time-velocity integral of A (r = -0.70, p < 0.01). CONCLUSIONS: Dobutamine improved the afterload mismatch of the LA booster pump function. This effect may have been due to the reduction in LV operational chamber stiffness, resulting in an increase in the LA forward ejection into the LV.

Animals↗

Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons.

Dendritic spines serve as preferential sites of excitatory synaptic connections and are pleomorphic. To address the structure-function relationship of the dendritic spines, we used two-photon uncaging of glutamate to allow mapping of functional glutamate receptors at the level of the single synapse. Our analyses of the spines of CA1 pyramidal neurons reveal that AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptors are abundant (up to 150/spine) in mushroom spines but sparsely distributed in thin spines and filopodia. The latter may be serving as the structural substrates of the silent synapses that have been proposed to play roles in development and plasticity of synaptic transmission. Our data indicate that distribution of functional AMPA receptors is tightly correlated with spine geometry and that receptor activity is independently regulated at the level of single spines.

Animals↗

Severe cardiac toxicity in hematological stem cell transplantation: predictive value of reduced left ventricular ejection fraction.

Eighty patients receiving hematological stem cell transplantation (HCT) with a preparative regimen consisting of total body irradiation (12.5 Gy), cyclophosphamide (4000 or 4500 mg/m2), and thiotepa (400 mg/m2) were evaluated for the development of cardiac toxicity. Patients in whom the pretransplant cumulative dose of anthracycline was more than or equal to 300 mg/m2 showed a lower left ventricular ejection fraction (EF) before HCT compared to patients with less than 300 mg/m2 (0.61 +/- 0.09 vs 0.67 +/- 0.06, P = 0.0010). Patients who had undergone more than or equal to six courses of chemotherapy showed a decreased EF before HCT compared to those after less than six courses (0.67 +/- 0.05 vs 0.63 +/- 0.09, P = 0.03). Three of seven patients (43%) whose pretransplant EF had been less than or equal to 0.55 developed severe cardiac toxicity, characterized by congestive heart failure (CHF) compared with none of 83 patients (0%) whose pretransplant EF had been more than 0.55 (P = 0.00026). Of the three patients who developed severe cardiac toxicity, two were given more than 300 mg/m2 of cumulative anthracycline and underwent 23 courses and six courses of chemotherapy, while the other patient received only two courses of chemotherapy with a total dose of 139 mg/m2 of anthracycline. These results indicate that an increased cumulative dose of anthracycline and number of chemotherapy treatments are correlated with a decrease of the EF and that the EF before HCT is useful for predicting the risk of cardiac complications for recipients who have received chemotherapy.

Adolescent↗

Immune reconstitution assessed during five years after allogeneic bone marrow transplantation.

Immune reconstitution is an important component of successful allogeneic bone marrow transplantation. Immune reconstitution was evaluated for 5 years after transplantation. While the number of CD8+ T cells and CD56+ cells recovered early post transplantation, a low number of CD4+ and CD4+ CD45RA+ T cells and reversal of the CD4/CD8 ratio continued up to 5 years. Although early recovery of IgG and IgM was seen at day 100 post transplantation, serum concentration of IgA was below the normal range at 6 months and increased gradually up to 5 years. Development of acute GVHD did not affect the numbers of CD4+, CD8+, CD4+ CD45RA+ and CD4+ CD29+ T cells, but the number of CD56+ cells in patients who developed grades II-IV acute GVHD was low. The number of CD4+ CD29+ T cells had a tendency to be higher in the patients with extensive chronic GVHD than in those without chronic GVHD 2 years after transplantation whereas the number of CD4+ CD45RA+ T cells was low in spite of the absence of chronic GVHD. Serum concentration of IgA was lower in patients with extensive chronic GVHD than in those without chronic GVHD at 180 days. The number of CD4+ CD45RA+ cells in 10-19-year-old patients was higher than that in 40-49-year-old patients. Response to the Con A and PHA in 10-19-year-old patients was higher than that in older patients at 1 and 2 years. There was no significant difference in the ability of immune reconstitution between related transplant recipients and unrelated transplant recipients. These results suggest that chronic GVHD and age of patients affected immune reconstitution post transplant.

Adolescent↗

Predominant inner-half wall thickening of left ventricle is attenuated in dilated cardiomyopathy: an application of tissue Doppler tracking technique.

The importance of the inner half (IH) of the left ventricular (LV) wall has been reported in hearts that contract normally. However, it is difficult to verify this fact in an in vivo human heart with clinical echocardiography. By using a recently developed tissue Doppler tracking technique, we could assess the systolic wall thickening of the IH and outer half (OH) of the LV wall in 11 normal and 7 dilated cardiomyopathic hearts. Percent wall thickening and the fractional contribution of the IH and OH to the transmural wall thickening were calculated. In healthy subjects, percent wall thickening of the IH, OH, and transmural wall of the left ventricle were 75.8% +/- 24.1%, 39.4% +/- 14.4% (P <.001 versus IH), and 57.6% +/- 17.6%, respectively. In patients with dilated cardiomyopathy, those values were 31.3% +/- 17.1%, 31.2% +/- 20.1% (not significant versus IH), and 31.2% +/- 16.5%, respectively. On the other hand, the fractional contributions of the IH and OH were 66.2% +/- 7.7% and 33.8% +/- 7.7% (P &lt.01 versus IH) in healthy subjects and 50.5% +/- 11.8% and 49.5% +/- 11.8% (not significant versus IH) in patients with dilated cardiomyopathy. Specifically, the IH contributed to the transmural wall thickening nearly twice as much as the OH did in healthy subjects, however, the predominance of IH contribution was attenuated in dilated cardiomyopathy. The tissue Doppler tracking technique is useful in assessing the IH and OH LV wall thickening separately in the clinical situation.

Adult↗

The importance of pulmonary venous flow measurement for evaluating left ventricular end-diastolic pressure in patients with coronary artery disease in the early stage of diastolic dysfunction.

Transmitral flow pattern assessed by pulsed Doppler echocardiography is widely used to evaluate left ventricular end-diastolic pressure (LVEDP). A restrictive mitral flow pattern is well recognized as a finding of severely elevated LVEDP. On the other hand, an abnormal relaxation pattern can be interpreted many ways. For example, some patients who display an abnormal relaxation pattern have a mild impairment of left ventricular (LV) relaxation as a result of aging, and others have severely impaired LV diastolic function. To evaluate LVEDP in patients with abnormal relaxation mitral filling patterns, we studied 55 patients who had coronary artery disease with abnormal relaxation pattern who underwent elective cardiac catheterization. We recorded the transmitral and pulmonary venous flow velocity curves and measured the duration of the mitral A wave (MAd) and pulmonary venous reversal wave during atrial contraction (PAd). Positive correlations were found between PAd and LVEDP (r = 0.65, P <.01) and between PAd-MAd and LVEDP (r = 0.7, P <.0001); however, MAd was not significantly correlated with LVEDP. In conclusion, PAd must be measured for an accurate evaluation of LV end-diastolic pressure in patients with an abnormal relaxation pattern in the transmitral flow velocity curve.

Aged↗

New method of on-line quantification of regional wall motion with automated segmental motion analysis.

We have recently developed an automated segmental motion analysis (A-SMA) system, based on an automatic "blood-tissue interface" detection technique, to provide real-time and on-line objective echocardiographic segmental wall motion analysis. To assess the feasibility of A-SMA in detecting regional left ventricular (LV) wall motion abnormalities, we performed 2-dimensional echocardiography with A-SMA in 13 healthy subjects, 22 patients with prior myocardial infarction (MI), and 9 with dilated cardiomyopathy (DCM). Midpapillary parasternal short-axis and apical 2- and 4-chamber views were obtained to clearly trace the blood-tissue interface. The LV cavity was then divided into 6 wedge-shaped segments by A-SMA. The area of each segment was calculated automatically throughout a cardiac cycle, and the area changes of each segment were displayed as bar graphs or time-area curves. The systolic fractional area change (FAC), peak ejection rate (PER), and filling rate (PFR) were also calculated with the use of A-SMA. In the control group, a uniform FAC was observed in real time among 6 segments in the short-axis view (60% +/- 10% to 78% +/- 9%), or among 5 segments in either the 2-chamber (59% +/- 12% to 75% +/- 16%) or 4-chamber view (58% +/- 13% to 72% +/- 12%). The variations of FAC, PER, and PFR were obviously decreased in infarct-related regions in the MI group and were globally decreased in the DCM group. We conclude that A-SMA is an objective and time-saving method for assessing regional wall motion abnormalities in real time. This method is a reliable new tool that provides on-line quantification of regional wall motion.

Adult↗

Compensatory responses of left atrial conduit flow to atrial fibrillation with acute myocardial infarction in a canine model.

The aim of this study was to examine the interaction of acute atrial fibrillation (Af) and acute myocardial infarction (AMI) on left atrial (LA) and left ventricular (LV) filling in atrioventricular (A-V) sequential paced, open chest, anesthetized dogs. Left atrial conduit function was determined from pulmonary venous flow (PVF) and detailed analysis of early diastolic flow with the use of micromanometers and transmitral Doppler echocardiography. We studied 8 dogs with regular ventricular rates to avoid the confounding effect of ventricular arrhythmia in Af. In the control stage, Af increased the diastolic PVF volume to the left atrium compared with that during regular A-V pacing (from 0.58 +/- 0.11 mL/beat to 0.70 +/- 0.13 mL/beat, P <.05), as a compensatory response to the impaired systolic PVF volume (from 0.56 +/- 0.12 mL/beat to 0.41 +/- 0.11 mL/beat, P <.05). As a result, cardiac output was maintained. However, in the AMI stage, Af decreased cardiac output (from 0.95 +/- 0.32 L/min to 0.80 +/- 0.23 L/min, P <.05 versus AMI with A-V pacing), and decreased diastolic PVF volume (from 0.46 +/- 0.13 mL/beat to 0.33 +/- 0.14 mL/beat, P <.05 versus AMI with A-V pacing). These changes were associated with a prolonged LV isovolumic pressure decay rate. Our study demonstrates that Af does not affect cardiac output in the setting of normal LV function at a controlled ventricular rate because enhanced LA conduit flow compensates for impaired LA reservoir function. In contrast, in the setting of AMI, the compensatory response to Af is attenuated because of abnormal LV relaxation, resulting in a decrease in cardiac output.

Animals↗

The induction of angiogenesis by the implantation of autologous bone marrow cells: a novel and simple therapeutic method.

BACKGROUND: Bone marrow contains many kinds of primitive cells that could differentiate to endothelial cells and secrete several growth factors. In the current study, we attempted to induce therapeutic angiogenesis by implanting autologous bone marrow cells (BMCs) and using a rat ischemic hind limb model. METHODS: BMCs were prepared by removing red blood cells. A rat ischemic hind limb model was made by the ligation of the left femoral artery and its branches. BMCs were injected into 7 points of the ischemic muscles. To assess angiogenesis, a microangiogram, laser Doppler, and histologic evaluation were performed after the surgical procedure. RESULTS: A microangiogram and histologic evaluation showed that angiogenesis was significantly induced in the ischemic hind limb by the implantation of BMCs. Laser Doppler imaging analysis showed that blood flow was significantly increased after implantation of BMCs. Some implanted BMCs were stained positively with CD31 and vascular endothelial-cadherin (VE-cadherin), which might have been incorporated into the vasculature. The condition of ischemia caused an elevation in the level of basic fibroblast growth factor in the ischemic muscle and also in interleukin-1beta derived from the implanted BMCs, which might contribute to angiogenesis. CONCLUSION: These findings indicate that autologous bone marrow implantation may be a novel and simple method for inducing therapeutic angiogenesis.

Animals↗

Click- and short tone burst-evoked myogenic potentials in cerebellopontine angle tumors.

We report results of vestibular-evoked myogenic potentials (VEMPs) in patients with cerebellopontine angle tumors and compare results obtained using clicks with those obtained using 500 Hz short tone bursts (STB). We reviewed the records of 87 patients with cerebellopontine angle tumors. Clicks (0.1 ms, 95 dB nHL) were presented to all patients and STB (500 Hz, rise/fall time 1 ms, plateau time 2 ms, 95 dB nHL) were presented to 27 patients. Click-evoked VEMPs were abnormal in 69/87 patients (79%; no response in 55 patients, decreased response in 14 patients, normal response in 18 patients). STB-evoked VEMPs were abnormal in 22/27 patients (82%; no response in 18 patients, decreased response in 4 patients, normal response in 5 patients). Click- and STB-evoked VEMPs were identical in 23/27 patients (85%). Two patients showed normal STB-evoked VEMPs and decreased click- evoked VEMPs, and 2 patients showed decreased STB-evoked VEMPs and absent click- evoked VEMPs. These results confirm our previous study in a small number of patients. Vestibular afferents seem to respond better to 500 Hz STBs than to clicks.

Adolescent↗

Influence of timing and magnitude of arterial wave reflection on left ventricular relaxation.

The influence of timing and magnitude of arterial wave reflection (WR) on afterload-dependent relaxation was evaluated in patients with a variety of heart diseases (group 1, age < 30 yr; group 2, age > 40 yr) and in dogs. While both femoral arteries were compressed (FC), WR returned just after the dicrotic notch (early diastole) in group 1 but before the dicrotic notch (late systole) in group 2. The time constant of the left ventricular pressure decay (tau) was shortened during FC in group 1, whereas it was prolonged in group 2. In dogs, a constriction of the thoracic aorta induced a late systolic augmentation of WR with a prolongation of tau (cf. group 2), whereas constriction of the lower abdominal aorta induced an early diastolic augmentation of WR with a shortening of tau (cf. group 1). With aortic constriction, coronary flow increased, and there was a close correlation between the peak change in backward aortic pressure and that in coronary flow regardless of the timing of WR. Thus the time at which WR returns during the cardiac cycle may have an important effect on left ventricular relaxation and coronary flow.

Adult↗

Appropriate dosing of pilsicainide hydrochloride in patients on hemodialysis.

Appropriate dosing of pilsicainide hydrochloride, an anti-arrhythmic drug excreted via the kidney, was investigated in patients on dialysis. Ten chronic hemodialysis patients with coexisting severe palpitation of supraventricular premature contractions (SVPC) were treated with 25 mg of pilsicainide hydrochloride before dialysis. All of their plasma concentrations were maintained within the therapeutic range and their mean dialysis rate was 32%. After 2 weeks, 7 patients were followed with consecutive daily dose treatment. In 3 of them, the dosage was returned to the single pre-dialysis administration because of the elevated plasma concentration reaching the toxic range 1 month after the start of administration. The dose schedule was maintained, and plasma pilsicainide concentrations remained within the therapeutic range during the 6-month follow-up. No abnormal findings were found in any parameters of electrocardiography, echocardiography or biochemistry. The number of SVPC diminished > 90% compared to the pretreatment level.

Anti-Arrhythmia Agents↗