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Biomedical subjects

A Kawamoto

Publications and source records attributed to A Kawamoto.

At least 19 recordsLinked to original sources

Proximity of pseudogapped superconductor and commensurate antiferromagnet in a quasi-two-dimensional organic system.

We performed the single-crystal 13C NMR studies on a quasi-two-dimensional system, deuterated kappa-(BEDT-TTF)2Cu[N(CN)(2)]Br, which is just on the border of the Mott transition. The NMR spectra are separated into two parts coming from the metallic (superconducting) and insulating phases due to the phase separation at low temperature. The examination of the separated spectra revealed that the Mott transition in this system is characterized by the first-order transition between the pseudogapped superconductor and the simplest commensurate antiferromagnet with a moment of 0.26 mu(B)/dimer.

Journal Article↗

Ferromagnetic and antiferromagnetic fluctuations of pi-d itinerant electrons disclosed by band-selective NMR.

We present a band-selective NMR method to probe the constituent electronic bands separately in the condensed molecular matter. This method is applied to an organic-inorganic pi-d hybrid metal, and its utility to give the static and dynamic spin susceptibilities for the constituent bands is demonstrated. The analysis of the results uncovers an exotic feature; the antiferromagnetic and ferromagnetic correlations are enhanced in separate bands in a single material. This finding provides a novel scope connecting the metal-insulator transitions in this system and the manganese oxides.

Journal Article↗

Ischemic preconditioning upregulates vascular endothelial growth factor mRNA expression and neovascularization via nuclear translocation of protein kinase C epsilon in the rat ischemic myocardium.

Ischemic preconditioning (IP) exerts cardioprotection through protein kinase C (PKC) activation, whereas myocardial ischemia enhances vascular endothelial growth factor (VEGF) mRNA expression. However, the IP effect or the involvement of PKC on the VEGF expression is unknown in myocardial infarction. We investigated whether IP enhances VEGF gene expression and angiogenesis through PKC activation in the in vivo myocardial infarction model. Sprague-Dawley rats were assigned into the following 3 groups: the sham group; the IP group, which underwent 3 cycles of 3 minutes of ischemia and 5 minutes of reperfusion (IP procedure); and the non-IP group. The latter 2 groups were subsequently subjected to left anterior descending coronary artery occlusion. To examine the involvement of PKC, the PKC inhibitor chelerythrine (5 mg/kg) or bisindolylmaleimide (1 mg/kg) was injected intravenously before the IP procedures. PKCepsilon was translocated to the nucleus after 10 minutes of ischemia after the IP procedure but was not translocated in the non-IP and the sham groups. VEGF mRNA expression 3 hours after infarction was significantly higher in the IP group than in the non-IP and the sham groups. Capillary density in the infarction was significantly higher, whereas the infarct size was smaller in the IP group than in the non-IP group at 3 days of infarction. Chelerythrine but not bisindolylmaleimide blocked all of the IP effects on the nuclear translocation of PKCepsilon, enhancement of VEGF mRNA expression and angiogenesis, and infarct size limitation. These results show that IP may enhance VEGF gene expression and angiogenesis through nuclear translocation of PKCepsilon in the infarcted myocardium.

Active Transport, Cell Nucleus↗

Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia.

BACKGROUND: We investigated the therapeutic potential of ex vivo expanded endothelial progenitor cells (EPCs) for myocardial neovascularization. METHODS AND RESULTS: Peripheral blood mononuclear cells obtained from healthy human adults were cultured in EPC medium and harvested 7 days later. Myocardial ischemia was induced by ligating the left anterior descending coronary artery in male Hsd:RH-rnu (athymic nude) rats. A total of 10(6) EPCs labeled with 1,1'-dioctadecyl-1 to 3,3,3',3'-tetramethylindocarbocyanine perchlorate were injected intravenously 3 hours after the induction of myocardial ischemia. Seven days later, fluorescence-conjugated Bandeiraea simplicifolia lectin I was administered intravenously, and the rats were immediately killed. Fluorescence microscopy revealed that transplanted EPCs accumulated in the ischemic area and incorporated into foci of myocardial neovascularization. To determine the impact on left ventricular function, 5 rats (EPC group) were injected intravenously with 10(6) EPCs 3 hours after ischemia; 5 other rats (control group) received culture media. Echocardiography, performed just before and 28 days after ischemia, disclosed ventricular dimensions that were significantly smaller and fractional shortening that was significantly greater in the EPC group than in the control group by day 28. Regional wall motion was better preserved in the EPC group. After euthanization on day 28, necropsy examination disclosed that capillary density was significantly greater in the EPC group than in the control group. Moreover, the extent of left ventricular scarring was significantly less in rats receiving EPCs than in controls. Immunohistochemistry revealed capillaries that were positive for human-specific endothelial cells. CONCLUSIONS: Ex vivo expanded EPCs incorporate into foci of myocardial neovascularization and have a favorable impact on the preservation of left ventricular function.

Animals↗

Vascular endothelial growth factor mRNA synthesis by peripheral blood mononuclear cells in patients with acute myocardial infarction.

We studied vascular endothelial growth factor (VEGF) mRNA synthesis by peripheral blood mononuclear cells (PBMCs) in 30 patients with acute myocardial infarction (AMI) and 20 healthy individuals. PBMCs were isolated from all patients on days 3 and 14 after the onset of aMI, and from all of control individuals. To prepare samples containing identical amounts of GAPDH cDNA, competitive PCR was performed by co-amplifying serial dilutions of GAPDH mutant templates. Next, to measure VEGF cDNA quantitatively in the samples containing identical amounts of GAPDH, we also used competitive PCR by co-amplifying mutant templates of VEGF. The serum VEGF concentrations on day 14 in patients with aMI were measured by an ELISA method. Higher levels of VEGF mRNA in PBMCs were present on day 14 than either on day 3 or in the control group. Serum VEGF concentrations correlated with the VEGF mRNA levels of PBMCs on day 14. Peak serum CK levels correlated well with VEGF mRNA levels of PBMCs on day 14. The present findings suggest that PBMCs may be one of the candidates responsible for elevated circulatory VEGF protein following aMI. In addition, VEGF mRNA may be overexpressed in PBMCs in response to cardiac muscle damage.

Aged↗

Bone marrow as a source of endothelial cells for natural and iatrogenic vascular repair.

Postnatal neovascularization has previously been considered synonymous with angiogenesis, but the finding that circulating endothelial progenitor cells (EPCs) may home to sites of neovascularization and there differentiate into endothelial cells (ECs) is consistent with "vasculogenesis," through which the primordial vascular network is established in the embryo. Our findings suggest that growth and development of new blood vessels in the adult are not restricted to angiogenesis but encompass vasculogenesis as well, although the proportional contributions remain to be clarified. Likewise, augmented or retarded neovascularization probably involves enhancement or impariment of the vasculogenesis process.

Animals↗

HMG-CoA reductase inhibitor mobilizes bone marrow--derived endothelial progenitor cells.

Endothelial progenitor cells (EPCs) have been isolated from circulating mononuclear cells in peripheral blood and shown to incorporate into foci of neovascularization, consistent with postnatal vasculogenesis. These circulating EPCs are derived from bone marrow and are mobilized endogenously in response to tissue ischemia or exogenously by cytokine stimulation. We show here, using a chemotaxis assay of bone marrow mononuclear cells in vitro and EPC culture assay of peripheral blood from simvastatin-treated animals in vivo, that the HMG-CoA reductase inhibitor, simvastatin, augments the circulating population of EPCs. Direct evidence that this increased pool of circulating EPCs originates from bone marrow and may enhance neovascularization was demonstrated in simvastatin-treated mice transplanted with bone marrow from transgenic donors expressing beta-galactosidase transcriptionally regulated by the endothelial cell-specific Tie-2 promoter. The role of Akt signaling in mediating effects of statin on EPCs is suggested by the observation that simvastatin rapidly activates Akt protein kinase in EPCs, enhancing proliferative and migratory activities and cell survival. Furthermore, dominant negative Akt overexpression leads to functional blocking of EPC bioactivity. These findings establish that augmented mobilization of bone marrow-derived EPCs through stimulation of the Akt signaling pathway constitutes a novel function for HMG-CoA reductase inhibitors.

Animals↗

[Significance of retardation of abnormal uptake of iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid myocardial scintigraphy in patients with vasospastic angina].

OBJECTIVES: This study investigated retardation of abnormal uptake of iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid(BMIPP) scintigraphy in patients with vasospastic angina. METHODS: Twenty-three patients with vasospastic angina showed abnormal uptake of BMIPP before medical treatment and had coronary vasospasm induced by acetylcholine. The patients were divided into two groups according to uptake of BMIPP after medical treatment: retardation of abnormal uptake of BMIPP(Group R, n = 4) and normal uptake of BMIPP(Group N, n = 19). Frequency of chest pain, medical treatment and autonomic nervous activity were compared between the two groups. Furthermore, the frequency of chest pain and uptake of BMIPP in group R were obtained after intensive medical treatment. Autonomic nervous activity was evaluated by heart rate variability on Holter electrocardiography. Heart rate variability contained high-frequency elements(HF; 0.15-0.4 Hz) and low-frequency elements(LF; 0.04-0.15 Hz). LF/HF was estimated for sympathetic nervous activity and HF was estimated for parasympathetic nervous activity. Daytime and nighttime autonomic nervous activity were compared between the two groups. RESULTS: The frequency of chest pain was higher in Group R than in Group N(p < 0.05). Medical treatment was not different between the two groups. Circadian variation of sympathetic and parasympathetic nervous activity were absent in Group R. During the nighttime, Group R showed higher sympathetic nervous activity(p < 0.05) and lower parasympathetic nervous activity(p < 0.01) than Group N. The frequency of chest pain was significantly lower after intensive medical treatment(p < 0.05), and uptake of BMIPP returned to normal in Group R. We suspected that the disorder in autonomic nervous activity was more severe in Group R, and thus induced coronary vasospasm. CONCLUSIONS: Retardation of abnormal uptake of BMIPP in patients with vasospastic angina indicates poor control of coronary vasospasm. Uptake of BMIPP is useful in the evaluation of coronary vasospasm control in such patients.

Adult↗

Efficacy of adding multiple doses of oxitropium bromide to salbutamol delivered by means of a metered-dose inhaler with a spacer device in adults with acute severe asthma.

BACKGROUND: The efficacy of combination therapy adding multiple doses of anticholinergics to beta(2)-agonists to improve outcome has not been established in adults with acute severe asthma. OBJECTIVE: This study was undertaken to compare the outcome of adults with acute severe asthma treated with 4 puffs of salbutamol (100 microg/actuation) every 20 minutes for 3 doses plus 4 puffs of oxitropium bromide (100 microg/actuation) with each of the 3 salbutamol doses versus salbutamol alone administered by means of a metered-dose inhaler with a spacer device. METHODS: A randomized, single-blind, placebo-controlled study was performed in 74 patients between 18 and 55 years old presenting to the emergency department (ED) for treatment of acute asthma with a peak expiratory flow (PEF) of 50% or less than the normal predicted value. The primary endpoint was improvement in PEF over the course. The secondary endpoint was the need for additional ED treatment at 120 minutes. RESULTS: The increase in PEF over the course was significantly greater in the oxitropium plus salbutamol treatment group (P <.0001). The mean absolute difference in PEF at 120 minutes for combination therapy compared with salbutamol alone was 37.8 L/min (P =.001). In addition, the proportion of need for additional ED treatment was less in the combination group than the group receiving salbutamol alone (odds ratio, 0.32; 95% confidence interval, 0.11-0.90). CONCLUSION: Adding multiple doses of oxitropium bromide to salbutamol delivered by means of a metered-dose inhaler with a spacer device for acute severe asthma produces a significant improvement in lung function and reduces the need for additional ED treatment.

Acute Disease↗

Two-color fluorescence staining of lectin and anti-CD46 antibody to assess acrosomal status.

OBJECTIVE: To examine potential methods for distinguishing between the acrosome reaction and acrosomal loss. DESIGN: Prospective randomized study. SETTING: Department of Obstetrics and Gynecology, Osaka University Hospital, Suita, Japan. PATIENT(S): Five healthy volunteers and 34 patients with normozoospermia who were participating in an IVF program. INTERVENTION(S): Semen samples were collected from the volunteers before the hamster egg penetration assay and from the patients at the time of IVF. MAIN OUTCOME MEASURE(S): The numbers of oocytes penetrated and spermatozoa bound were determined with the hamster egg penetration assay. Acrosomal status was assessed with two-color fluorescence staining using fluorescein isothiocyanate-conjugated Pisum sativum agglutinin (FITC-PSA) and MH61 (anti-CD46 monoclonal antibody) with Texas red-conjugated antimouse immunoglobulin G antiserum. RESULT(S): The MH61 monoclonal antibody inhibited the penetration of human spermatozoa into hamster oocytes but did not reduce the number of spermatozoa bound to the zona-free hamster oocytes. Two-color fluorescence staining revealed four staining patterns of the acrosomal region. The percentage of PSA-negative/CD46-positive spermatozoa increased to a greater extent than that of PSA-negative/CD46-negative spermatozoa with an increase in the incubation time. CONCLUSION(S): Two-color fluorescence staining with FITC-PSA and the anti-CD46 monoclonal antibody may be useful for distinguishing between the acrosome reaction and acrosomal loss.

Acrosome↗

Endometrial development was improved by transdermal estradiol in patients treated with clomiphene citrate.

The objective of this study was to examine the effect of transdermal estrogen therapy on the endometrial thickness and serum hormone levels in anovulatory patients treated with clomiphene citrate (CC). There was a significant difference in endometrial thickness between the CC + transdermal estrogen group and the CC only group from day -2 to day +2. Serum estradiol (E2) levels in the CC + transdermal estrogen group were significantly higher than those in the CC only group on day -2 and day 0. Our results support that addition of transdermal E2 to the treatment protocol of the women treated with CC elicited a favorable response of the endometrium.

Administration, Cutaneous↗

A case of eosinophilic myocarditis complicated by Kimura's disease (eosinophilic hyperplastic lymphogranuloma) and erythroderma.

This report describes a patient with eosinophilic myocarditis complicated by Kimura's disease (eosinophilic hyperplastic lymphogranuloma) and erythroderma. A 50-year-old man presented with a complaint of precordial pain. However, the only abnormal finding on examinatioin was eosinophilia (1617 eosinophils/microl). Three years later, the patient developed chronic eczema, and was diagnosed with erythroderma posteczematosa. One year later, a tumor was detected in the right auricule, and a diagnosis of Kimura's disease was made, based on the biopsy findings. The patient developed progressive dyspnea 6 months later and was found to have cardiomegaly and a depressed left ventricular ejection fraction (17%). A diagnosis of eosinophilic myocarditis was made based on the results of a right ventricular endomyocardial biopsy. The eosinophilic myocarditis and erythrodrema were treated with steroids with improvement of both the eosinophilia and left ventricular function.

Angiolymphoid Hyperplasia with Eosinophilia↗

[An elderly case of triple-vessel coronary artery disease with alternating bundle branch blocks in serial electrocardiograms].

An 82-year-old woman was admitted with severe chest pain and orthopnea on January 17, 1997. Physical examination revealed bilateral leg edema and cyanosis at the periphery of the extremities. The serum CK level was 488 IU/l on admission and increased to a maximum value of 4,866 IU/l 8 hours after admission. An echocardiogram demonstrated diffuse severe hypokinesis in the left ventricle. Serial electrocardiograms showed transient right bundle branch block, left bundle branch block, and normal sinus rhythm. The patient was diagnosed as having congestive heart failure. Artificial ventilation was performed, and furosemide, isosorbide dinitrate and dopamine were administered. A right ventricular endomyocardial biopsy performed on the 13th hospital day demonstrated moderate hypertrophy and disparity of cardiac myocytes and fibrosis around the myocytes, and few inflammatory cells in the specimens. This biopsy finding was not compatible with acute myocarditis but with the chronic stage of myocarditis. The patient was discharged on the 45th hospital day, but returned because of a recurrence of congestive heart failure. After an improvement of the heart failure, a coronary angiography was performed on the 20th hospital day. The coronary angiography revealed significant stenosis in three vessels. This elderly patient had congestive heart failure and triple-vessel coronary artery disease with transient alternating bundle branch blocks on serial electrocardiograms. Alternating bundle branch blocks and diffuse left ventricular dysfunction was considered to be induced by the aging process, postmyocarditic change of myocytes, and triple-vessel coronary artery disease in this case.

Aged↗

Phylogenic analysis of echovirus type 30 isolated from a large epidemic of aseptic meningitis in Japan during 1997-1998.

During 1997 to 1998, a nationwide epidemic of aseptic meningitis occurred in Japan. More than 4,500 isolates from patients with aseptic meningitis were identified as echovirus type 30. To investigate the character of these isolates, we examined the nucleotide sequences of thirty-seven geographical representatives and compared them with 50 strains isolated during the past 20 years. The phylogenic analysis used partial sequences from either the VP1 or VP4-VP2 region of the viral capsid. This analysis revealed that the isolates were divided into six genomic groups. All isolates identified during 1997-1998 belonged to only two genomic groups; these two groups are thought to be the causative viral agents involved in the recent epidemic.

Enterovirus B, Human↗

Serum levels of VEGF and basic FGF in the subacute phase of myocardial infarction.

We examined serial changes in serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) measured by ELISAs in 45 patients with acute myocardial infarction (AMI) who received heparin intravenously for 3 to 5 days after the onset and in 30 control subjects with an old myocardial infarction. To evaluate the effect of heparin on these serum levels, heparin was administered intravenously in 10 patients with AMI on day 21. Blood samples were obtained from all AMI patients on days 1, 2, 3, 7, 14, 21, and 28 and from 10 AMI patients before and 1 h after heparin administration. Serum VEGF level was significantly reduced after heparin administration (P<0.001). Serum samples from day 1 to 3 were therefore excluded from the subsequent analysis. Serum VEGF level in AMI patients was significantly higher on day 7 than in the control subjects (P<0.0001), and then decreased over time (P<0.0001). The serum VEGF level on day 7 was independently associated with the peak serum CK level (P<0.05). The serum bFGF level did not differ significantly between the AMI patients and the control subjects. In conclusion, the serum VEGF level may be selectively elevated during the healing process after AMI.

Anticoagulants↗

Estimation of coronary flow reserve by intracoronary administration of nicorandil: comparison with intracoronary administration of papaverine.

We investigated the usefulness of the intracoronary administration of nicorandil (NIC) compared with that of papaverine (PAP) in the evaluation of coronary flow reserve (CFR) in 17 patients, including 10 patients with old myocardial infarction and 7 patients with angina pectoris. CFR was measured with a Doppler guidewire inserted into the distal site of the left anterior descending coronary artery during intracoronary administration of 10 mg PAP, and of 0.5 mg, 1.0 mg, 2.0 mg, and 3.0 mg NIC. We examined the changes in heart rate (HR), mean blood pressure (mBP), the total score of QTc interval on a 12-lead electrocardiogram (sigma QTc), and ST-T segment, before and after drug administration. CFR was significantly lower during administration of 0.5 mg (1.9 +/- 0.9) and 1.0 mg (2.2 +/- 0.9) NIC than during administration of PAP (2.6 +/- 1.1) (P < 0.01). There was no significant difference in the CFR during administration of 2.0 mg (2.6 +/- 1.0) or 3.0 mg (2.5 +/- 1.0) NIC and that observed during administration of PAP. The CFR during administration of PAP was significantly correlated with that during administration of 2.0 mg NIC (r2 = 0.72, P < 0.0001) and 3.0 mg NIC (r2 = 0.70, P < 0.0001). PAP, but not NIC, significantly altered the HR, mBP, and sigma QTc. Inverted T waves were observed in 14 patients, and elevation of the ST segment was observed in 4 patients during administration of PAP (including 1 patient with ventricular tachycardia). The administration of 0.5 mg to 2.0 mg NIC was not associated with ST-T segment changes, except in 1 patient, but inverted T waves were observed in 2 patients and depression of the ST segment was observed in 2 patients during administration of 3.0 mg NIC. Intracoronary administration of NIC is useful and safe for evaluating the CFR. The appropriate dose for measuring CFR is 2.0 mg nicorandil.

Angina Pectoris↗