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Biomedical subjects

T Imaizumi

Publications and source records attributed to T Imaizumi.

At least 19 recordsLinked to original sources
PubMed1999

Predictors of death from congestive heart failure in hypertrophic cardiomyopathy.

In 309 patients with hypertrophic cardiomyopathy during long-term follow-up (mean 9.4 years), independent predictors of death from congestive heart failure (n = 15) were smaller electrocardiographic SV1 + RV5 and smaller echocardiographic fractional shortening at the initial evaluation. Our data may contribute to the construction of therapeutic strategies for the prevention of heart failure death in patients with hypertrophic cardiomyopathy.

Adolescent↗
PubMed1999

Endothelial injuries of coronary arteries distal to thrombotic sites: role of adhesive interaction between endothelial P-selectin and leukocyte sialyl LewisX.

Intracoronary thrombus formation is associated with epicardial vasoconstriction distal to the thrombotic site. To investigate the mechanisms of abnormal vasomotor function of the artery distal to the thrombotic site, we studied coronary vessels in dogs with cyclic flow variations (CFVs) of the left anterior descending coronary artery (LAD) stenosis with endothelial injury. Coronary rings isolated from the LAD (proximal, stenotic, and distal sites) and control circumflex coronary arteries were tested for responsiveness to endothelium-dependent (acetylcholine and A23187) and endothelium-independent vasodilators (NaNO2). Endothelium-independent relaxation was intact in all 4 sites. Endothelium-dependent relaxation was intact in the control and proximal sites and impaired in the stenotic sites. Relaxations not only to acetylcholine and A23187 but also to serotonin, ADP, and thrombin were impaired in the distal sites after observing CFVs for 80 minutes. Electron microscopy revealed the loss of endothelial integrity with leukocyte adherence to the endothelium in the distal sites. Immunohistochemical expression of P-selectin on the endothelial cells was more upregulated in the distal site than in the proximal site, and P-selectin mRNA expression was significantly greater in the ischemic region distal to the thrombotic site than in the proximal nonischemic region. PB1.3, a neutralizing monoclonal antibody against P-selectin, and sialyl LewisX (SLeX)-containing oligosaccharide SLeX, a carbohydrate analogue of selectin ligand, preserved endothelial function without affecting CFVs. SLeX-containing oligosaccharide preserved endothelial integrity of the distal site and inhibited P-selectin expression of the distal site. Thus, the adhesive interaction between endothelial P-selectin and leukocyte SLeX may play an important role in endothelial injuries of the coronary artery distal to the thrombotic site.

Animals↗
PubMed1999

Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis.

BACKGROUND: Exposure to risk factors such as hypertension or hypercholesterolemia decreases the bioavailability of endothelium-derived nitric oxide (NO) and impairs endothelium-dependent vasodilation. Recently, a circulating endogenous NO synthase inhibitor, asymmetric dimethylarginine (ADMA), has been detected in human plasma. The purpose of this study was to examine the relationship between plasma ADMA and atherosclerosis in humans. METHODS AND RESULTS: Subjects (n=116; age, 52+/-1 years; male:female ratio, 100:16) underwent a complete history and physical examination, determination of serum chemistries and ADMA levels, and duplex scanning of the carotid arteries. These individuals had no symptoms of coronary or peripheral artery disease and were taking no medications. Univariate and multivariate analyses revealed that plasma levels of ADMA were positively correlated with age (P<0.0001), mean arterial pressure (P<0.0001), and Sigma glucose (an index of glucose tolerance) (P=0.0006). Most intriguingly, stepwise regression analysis revealed that plasma ADMA levels were significantly correlated to the intima-media thickness of the carotid artery (as measured by high-resolution ultrasonography). CONCLUSIONS: This study reveals that plasma ADMA levels are positively correlated with risk factors for atherosclerosis. Furthermore, plasma ADMA level is significantly correlated with carotid intima-media thickness. Our results suggest that this endogenous antagonist of NO synthase may be a marker of atherosclerosis.

Adult↗
PubMed1999

The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop.

The Janus family of protein tyrosine kinases (JAKs) regulate cellular processes involved in cell growth, differentiation and transformation through their association with cytokine receptors. However, compared with other kinases, little is known about cellular regulators of the JAKs. We have recently identified a JAK-binding protein (JAB) that inhibits JAK signaling in cells. In the studies presented here we demonstrate that JAB specifically binds to the tyrosine residue (Y1007) in the activation loop of JAK2, whose phosphorylation is required for activation of kinase activity. Binding to the phosphorylated activation loop requires the JAB SH2 domain and an additional N-terminal 12 amino acids (extended SH2 subdomain) containing two residues (Ile68 and Leu75) that are conserved in JAB-related proteins. An additional N-terminal 12-amino-acid region (kinase inhibitory region) of JAB also contributes to high-affinity binding to the JAK2 tyrosine kinase domain and is required for inhibition of JAK2 signaling and kinase activity. Our studies define a novel type of regulation of tyrosine kinases and might provide a basis for the design of specific tyrosine kinase inhibitors.

Amino Acid Sequence↗
PubMed1999

The role of voltage-gated Ca2+ channels in anoxic injury of spinal cord white matter.

Dorsal column axons of the rat spinal cord are partially protected from anoxic injury following blockade of voltage-sensitive Na+ channels and the Na+/--Ca2+ exchanger. To examine the potential contribution of voltage-gated Ca2+ channels to anoxic injury of spinal cord axons, we studied axonal conduction in rat dorsal columns in vitro following a 60-min period of anoxia. Glass microelectrodes were used to record field potentials from the dorsal columns following distal local surface stimulation. Perfusion solutions containing blockers of voltage-gated Ca2+ channels were introduced 60 min prior to onset of anoxia and continued until 10 min after reoxygenation. Pharmacological blocking agents which are relatively selective for L- (verapamil, diltiazem, nifedipine) and N- (omega-conotoxin GVIA) type calcium channels were significantly protective against anoxia-induced loss of conduction, as was non-specific block using divalent cations. Other Ca2+ channel blockers (neomycin and omega-conotoxin MVIIC) that affect multiple Ca2+ channel types were also neuroprotective. Ni2+, which preferentially blocks R-type Ca2+ channels more than T-type channels, was also protective in a dose-dependent manner. These data suggest that the influx of Ca2+, through L-, N- and possibly R-type voltage-gated Ca2+ channels, participates in the pathophysiology of the Ca2+-mediated injury of spinal cord axons that is triggered by anoxia.

Animals↗
PubMed1999

Expression of the SART-1 tumor rejection antigen in breast cancer.

We investigated in breast cancers the expression of the SART-1 gene encoding tumor rejection antigens. SART-1 mRNA was expressed in all of the samples tested. The SART-1(800) antigen was detectable in 20 of 50 (40%) breast cancer tissues and all breast cancer cell lines tested, but not in normal breast tissues. The SART-1(800)+ breast cancer cells transfected with HLA-A2601 or HLA-A2402 cDNA were recognized by the HLA-A26-restricted and SART-1-specific cytotoxic T lymphocytes (CTLs) or the HLA-A24-restricted and SART-1-specific CTLs, respectively. Among the 20 SART-1(800)+ tumors, 9 or 8 tumors expressed estrogen receptor or progesterone receptor, respectively. Therefore, the patients with HLA-A26 or -A24 haplotype might be appropriate candidates for specific immunotherapy with the SART-1 peptides independently or in combination with hormone therapy.

Antigens, Neoplasm↗
PubMed1999

Comparison of ES cell fate in sandwiched aggregates and co-cultured aggregates during blastocyst formation by monitored GFP expression.

Markers and the means to detect them are required to monitor the fate of living cells. However, few suitable markers for living cells were known until a green fluorescent protein (GFP) was discovered. We have established mouse embryonic stem (ES) cell lines that express mutant GFP under the chicken beta-actin (CAG) promoter. Using these cell lines, we were able to follow the migration of ES cells during blastocyst formation both in sandwiching and coculture methods, even if only a single ES cell was used. Furthermore, the contribution of ES cells to the inner cell mass (ICM) was easily estimated at the blastocyst stage. We compared sandwiching with coculture aggregation relative to the contribution of the ES cell in the ICM, and the results indicated that there was no difference in the ratios of chimeric embryos having ICM contributed from cultured ES cells. Furthermore, an aggregated single ES cell was able to contribute three or four cells to the ICM at the blastocyst stage. Thus we conclude that one, instead of two, embryos is enough to make aggregation with ES cells, and a single ES cell attached to an embryo is enough to produce germline chimeras. Moreover, we could clearly observe single cell fate during blastocyst formation. This suggests that our established cell line can be used for monitoring single cell fate in vivo. In addition, we have shown that up to five doses of 30 sec of UV irradiation using GFP filters have no effect on the embryonic development.

Animals↗
PubMed1999

Coronary stent deployment in a young adult with Kawasaki disease and recurrent myocardial infarction.

A 19-year-old man developed a huge coronary aneurysm and stenosis in the right coronary artery as a sequela of Kawasaki disease (KD) that resulted in recurrent episodes of myocardial infarction. Coronary ischemic events were successfully prevented after balloon angioplasty followed by coronary stent implantation into the stenotic lesion. The stent deployment may have an advantage compared with balloon angioplasty and other new devices for the treatment for patients with KD showing stenotic lesions without dense calcification.

Adult↗
PubMed1999

Erythropoietic protoporphyria with fatal liver failure.

A 33-year-old woman with a history of photosensitivity, persistent abdominal pain, and liver dysfunction was admitted to our department because of abdominal pain and progression of liver dysfunction. On admission, levels of protoporphyrin and coproporphyrin within erythrocytes were markedly increased. Autofluorescent erythrocytes were also detected, leading to a diagnosis of erythropoietic protoporphyria. A liver biopsy specimen revealed cirrhosis with dark brown granules filling hepatocytes, bile canaliculi, and bile ductules. Transfusion of washed erythrocytes, hemodialysis, and administration of cholestyramine and beta-carotene transiently improved levels of porphyrins and liver function. The patient died of rupture of esophageal varices followed by multiple organ failure. However, the treatments were believed to have extended survival.

Adult↗
PubMed1999

Detection of concealed left sided accessory atrioventricular pathway by P wave signal averaged electrocardiogram.

OBJECTIVES: The purpose of this study was to examine whether P wave signal-averaged electrocardiogram (P-SAECG), which detects subtle changes in P wave, detects the concealed accessory atrioventricular pathway (AP). BACKGROUND: It is difficult to differentiate atrioventricular reciprocating tachycardia (AVRT) due to the AP from atrioventricular nodal reentrant tachycardia (AVNRT) when the ventricular preexcitation is absent on 12-lead electrocardiograms. By electrophysiological studies, the anterograde conduction in the concealed AP is shown to be blocked near the AP-ventricular interface during sinus rhythm. METHODS: P-SAECG during sinus rhythm was performed in 20 normal volunteers (control), 21 patients with AVRT due to the concealed AP, 19 with AVNRT, 22 with paroxysmal atrial fibrillation (PAF), and 7 with automatic atrial tachycardia (AT). The filtered P wave duration (FPD) and AR20 (power spectrum area ratio of 0-20 to 20-100 Hz) were measured and repeated in AVRT, AVNRT and AT groups at one week after catheter ablation. RESULTS: The anterograde conduction in the concealed left-sided AP was confirmed in all cases by an electrophysiological study. The FPD in AVRT group was more prolonged than that in controls or AVNRT group. Although the FPD was similar between AVRT and PAF groups, AR20 differentiated between the two groups. Ablation of the concealed AP shortened FPD in AVRT group but that of the slow pathway or the atrial focus did not shorten in the AVNRT or AT groups, respectively. The changes in FPD after ablation were correlated with those in the duration of atrial activity by an electrophysiological study (r=0.67). CONCLUSIONS: Our findings suggest that P-SAECG detects the concealed left-sided AP, providing a clinical tool in noninvasively assessing atrial activation patterns.

Adolescent↗
PubMed1999

Dispersion of filtered P wave duration by P wave signal-averaged ECG mapping system: its usefulness for determining efficacy of disopyramide on paroxysmal atrial fibrillation.

INTRODUCTION: Although it is desirable to know drug efficacy before initiating antiarrhythmic therapy, there have been no methods for this evaluation. P wave signal-averaged ECG (P-SAECG) is useful to detect subtle changes in disturbance of atrial conduction. The purpose of this present study was to test whether P-SAECG mapping system would give any information on the efficacy of disopyramide on the prevention of paroxysmal atrial fibrillation (PAF). METHODS AND RESULTS: P-SAECG was performed before disopyramide treatment, at 3 hours after a single dose of oral disopyramide (200 mg), and after 4 weeks of disopyramide treatment (300 mg/day). After measuring the filtered P wave duration by the vector magnitude and mapping methods, we calculated filtered P wave duration dispersion, difference between the maximal and minimal filtered P wave duration within 16 chest leads at these three time points. Filtered P wave duration and filtered P wave duration dispersion before treatment were longer in 32 patients with symptomatic PAF than in 31 healthy volunteers. Disopyramide was effective for suppression of PAF in 17 patients and ineffective in 15 patients after 4 weeks of treatment. Filtered P wave duration was similarly prolonged at 3 hours in the two groups, whereas filtered P wave duration dispersion at 3 hours after the disopyramide administration behaved differently; it decreased in all of the effective group and increased in all of the ineffective group. The effective patients were prospectively followed with the same treatment for 6 months. In 16 (94%) of these 17 effective patients, no PAF was documented and they remained to be asymptomatic. CONCLUSIONS: Thus, measuring filtered P wave duration dispersion with the P-SAECG mapping method after a single administration may predict the long-term efficacy of disopyramide in patients with PAF.

Administration, Oral↗
PubMed1999

Adhesive interaction between P-selectin and sialyl Lewis(x) plays an important role in recurrent coronary arterial thrombosis in dogs.

Cell adhesion molecules may play an important role in the disease process of acute coronary syndromes. We have shown a neutralizing anti-P-selectin monoclonal antibody and a sialyl Lewis(x)-containing oligosaccharide (SLe(x)-OS), an analogue of selectin ligand on leukocytes, reduce cyclic flow variations (CFVs) in a canine model of recurrent coronary arterial thrombosis, suggesting the important interaction between P-selectin and SLex for the pathophysiology of these syndromes. However, the functional role of these adhesion molecules in the thrombotic process remains unclear. Therefore, we investigated effects of SLe(x)-OS on CFVs, platelet P-selectin expression, and morphology of the stenotic site in the same model. Anesthetized open-chest dogs (n=34) were randomly divided into 4 groups after developing CFVs. Dogs intravenously received saline or graded doses of SLe(x)-OS (5, 20, or 40 mg/kg bolus) infusion followed by a continuous infusion (5 mg. kg-1. h-1) for 60 minutes. By flow cytometric analysis, P-selectin expression on platelets after CFVs was significantly upregulated during CFVs. Immunohistochemical analysis revealed the incorporation of platelets with upregulated P-selectin within thrombi at the stenotic site. Microscopic observations revealed the presence of numerous platelets adhered to leukocytes at the stenotic site on the damaged endothelium. SLe(x)-OS significantly reduced CFVs, inhibited the P-selectin expression on platelets, and prevented the adherence of platelets and leukocytes. These findings further support the notion that the adhesive interaction between P-selectin on platelets and SLe(x) on leukocytes plays an important role in platelet-mediated thrombus formation in this model.

Animals↗
PubMed1999

[Monozygotic twins with suspected hereditary sensory and autonomic neuropathy (HSAN) type V].

We report a pair of 1-year-5-month-old female monozygotic twins with generalized loss of pain sensation, but without impairment of other sensory modalities and the diaphoretic function. Routine electrophysiological investigations revealed no abnormalities. Morphometric analysis of biopsied sural nerve showed that the number of small myelinated fibers was reduced and that of unmyelinated fibers was normal or mildly reduced. On the basis of these findings, we suspected a diagnosis of a rare disorder, HSAN type V, which has not previously been reported in Japan.

Diseases in Twins↗
PubMed1999

Endothelial dysfunction by acute hyperhomocyst(e)inaemia: restoration by folic acid.

Recent evidence demonstrates that hyperhomocyst(e)inaemia is a novel risk factor for cardiovascular diseases. In patients with chronic hyperhomocyst(e)inaemia, endothelial function is impaired. However, whether hyperhomocyst(e)inaemia per se is a cause or an epiphenomenon of endothelial dysfunction remains unknown. In this study, we examined the effects of methionine-induced acute hyperhomocyst(e)inaemia on human endothelial function. In healthy volunteers we administered methionine (0.1 g/kg body weight, per os), a substrate of homocyst(e)ine, with or without folic acid (20 mg, per os) and examined flow-mediated vasodilatation of the brachial artery by high-resolution ultrasonography as a non-invasive measure of endothelial function. We also measured plasma levels of homocyst(e)ine before and 3, 8 and 24 h after methionine loading. Methionine administration increased plasma levels of homocyst(e)ine by four times the basal level at 8 h (P<0.0001, ANOVA). The plasma levels returned to baseline at 24 h. Flow-mediated vasodilatation was significantly decreased to half of the baseline value at 8 h and returned to baseline at 24 h (P<0.0001, ANOVA), whereas endothelium-independent vasodilatation by glyceryl trinitrate was not affected by the methionine loading. Co-administration of folic acid did not attenuate methionine-induced hyperhomocyst(e)inaemia but completely prevented endothelial dysfunction. Our results suggest that in humans a methionine-rich diet may acutely impair endothelial function, which can be prevented by folic acid supplementation.

Acute Disease↗