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Biomedical subjects

Satoshi Ogawa

Publications and source records attributed to Satoshi Ogawa.

At least 91 records · Page 5Linked to original sources
PubMed2004

Can the life span of human marrow stromal cells be prolonged by bmi-1, E6, E7, and/or telomerase without affecting cardiomyogenic differentiation?

BACKGROUND: Cell transplantation has recently been challenged to improve cardiac function of severe heart failure. Human mesenchymal stem cells (hMSCs) are multipotent cells that can be isolated from adult marrow stroma, but because of their limited life span, it is difficult to study them further. To overcome this problem, we attempted to prolong the life span of hMSCs and investigate whether the hMSCs modified with cell-cycle-associated genes can differentiate into cardiomyocytes in vitro. METHODS: We attempted to prolong the life span of hMSCs by infecting retrovirus encoding bmi-1, human papillomavirus E6 and E7, and/or human telomerase reverse transcriptase genes. To determine whether the hMSCs with an extended life span could differentiate into cardiomyocytes, 5-azacytidine-treated hMSCs were co-cultured with fetal cardiomyocytes in vitro. RESULT: The established hMSCs proliferated over 150 population doublings. On day 3 of co-cultivation, the hMSCs became elongated, like myotubes, began spontaneously beating, and acquired automaticity. Their rhythm clearly differed from that of the surrounding fetal mouse cardiomyocytes. The number of beating cardiomyocytes increased until 3 weeks. hMSCs clearly exhibited differentiated cardiomyocyte phenotypes in vitro as revealed by immunocytochemistry, RT-PCR, and action potential recording. CONCLUSIONS: The life span of hMSCs was prolonged without interfering with cardiomyogenic differentiation. hMSCs with an extended life span can be used to produce a good experimental model of cardiac cell transplantation and may serve as a highly useful cell source for cardiomyocytic transplantation.

Action Potentials↗
PubMed2004

Brain natriuretic peptide response is heterogeneous during beta-blocker therapy for congestive heart failure.

BACKGROUND: Plasma brain natriuretic peptide (BNP) levels are useful marker to guide medical treatment in patients with congestive heart failure (CHF). We tested the hypothesis that the plasma BNP concentration would be a useful marker of beta-blocker therapy for CHF. METHODS AND RESULTS: Eighty-four patients with New York Heart Association class II-IV CHF and a left ventricular ejection fraction (LVEF) <40% were treated with beta-blockers, including metoprolol and carvedilol, for at least 16 weeks. End-diastolic and end-systolic dimensions decreased, and radionuclide LVEF increased 4 weeks after introduction of beta-blockers (early phase). LV end-diastolic and end-systolic dimensions both decreased, and LVEF increased 16 to 48 weeks after the therapy (late phase). However, the BNP concentration did not change during the observation period. Overall LV function improved in all 4 subgroups divided according to the baseline BNP levels. CONCLUSIONS: Plasma BNP concentration is not a sensitive marker of successful beta-blocker therapy for CHF.

Adrenergic beta-Antagonists↗
PubMed2004

Autoantibodies against M2-muscarinic acetylcholine receptors: new upstream targets in atrial fibrillation in patients with dilated cardiomyopathy.

AIM: To characterise the clinical significance of M2-muscarinic acetylcholine receptor autoantibodies (M2-AAB) in patients with dilated cardiomyopathy (DCM). METHODS AND RESULTS: Sera from 104 patients with DCM, age-matched with 104 patients with idiopathic atrial fibrillation (Af) and 104 healthy control subjects, were screened for M2-AAB by enzyme-linked immunosorbent assay (ELISA). IgG purified by Protein-A column was also used as a primary antibody in ELISA. In DCM, M2-AAB were detected in 40% of patients using whole sera and in 36% of patients using purified IgG. M2-AAB were also found in several patients with idiopathic Af (23%, 23%), and these frequencies were significantly higher than those in healthy subjects (8%, 8%). Af was more common in AAB-positive than in AAB-negative patients with DCM. Multivariable analysis confirmed that M2-AAB were independent predictors of the presence of Af in such patients. We determined electrophysiological changes by adding patient purified M2-AAB to chick embryos. Purified IgG from both Af and DCM patients exhibited negative chronotropic effects and induced supraventricular arrhythmias. CONCLUSION: M2-AAB may play a role in mediating the development of Af in patients with DCM.

Atrial Fibrillation↗
PubMed2004

The expression of '150-kDa oxygen regulated protein (ORP-150)' in human brain and its relationship with duration time until death.

The expression of oxygen regulated protein 150-kDa (ORP-150) was strongly induced in human brain under the hypoxic conditions. We examined the expression of ORP-150 in the brain samples, and discussed its significance in forensic practice. The cerebral cortexes of 31 cases (asphyxia: 9 cases, hypothermia: 4, exsanguinations: 5, CO intoxication (CO): 6, sudden cardiac death (SCD): 7) were used for this study. Each tissue section was incubated with anti-ORP-150 polyclonal antibody and the number of ORP-150 positive cells were counted. In the multiple linear regression method, the estimated regression coefficient of ORP-150 on age was significant (P=0.039) thus, we could find that the ORP-150 expression level depended on age. Using analysis of covariance, we compared the means of ORP-150, LSMEAN, which means hypothetic average value excluding influence of age, for each cause of death. The LSMEAN+/-SE was 84.74+/-9.03 in hypothermia, 57.52+/-6.34 in asphyxia, 46.68+/-6.70 in CO, 24.84+/-8.05 in exsanguinations, and 16.24+/-7.35 in SCD. As a result of the analysis, the LSMEAN of the ORP-150 expression level was related to the cause of death. There might be differences in the duration of brain ischemia before death. For example, SCD is presumed to be instant death, while brain ischemia continues for several minutes in asphyxia, CO and exsanguinations, and for several hours in hypothermia cases. Therefore, the immunohistochemical and morphometrical analysis of ORP-150 in the brain may be very useful to determine the duration of brain ischemia before death in forensic autopsy cases.

Adolescent↗
PubMed2004

The 150-kilodalton oxygen-regulated protein ameliorates lipopolysaccharide-induced acute lung injury in mice.

The 150-kd oxygen-regulated protein is a novel stress protein that is located in the endoplasmic reticulum and contributes to cell survival when this organelle is under stress. Expression of this protein was strongly increased in alveolar macrophages and alveolar epithelial cells from mice with acute lung injury induced by lipopolysaccharide. Transgenic mice overexpressing the 150-kd protein showed decreased histological severity of this lung injury, accompanied by lower total protein concentrations, and lactate dehydrogenase activity in bronchoalveolar lavage fluid. As indicated by nick end-labeling, lipopolysaccharide induced apoptosis in fewer alveolar wall cells in transgenic than in wild-type mice. Transgenic mice also showed increased survival after lipopolysaccharide injection (a log-rank test). Thus, the 150-kd protein, an endoplasmic reticulum-related molecular chaperone, is pivotal in resisting acute lung injury from lipopolysaccharide.

Animals↗
PubMed2004

Cardiomyocytes undergo cells division following myocardial infarction is a spatially and temporally restricted event in rats.

Dividing cardiomyocytes are observed in autopsied human hearts following recent myocardial infarction, however there is a lack of information in the literature on the division of these cells. In this study we used a rat model to investigate how and when adult mammalian cardiomyocytes proliferate by cell division after myocardial infarction. Myocardial infarction was induced in Wistar rats by ligation of the left coronary artery. The rats were sacrificed periodically up to 28 days following induced myocardial infarction, and the hearts subjected to microscopic investigation. Cardiomyocytes entering the cell cycle were assayed by observation of nuclear morphology and measuring expression of Ki-67, a proliferating cell marker. Ki-67 positive cardiomyocytes and dividing nuclei were observed initially after 1 day. After 2 days dividing cells gradually increased in number at the ischemic border zone, reaching a peak increase of 1.12% after 3 days, then gradually decreasing in number. Dividing nuclei increased at the ischemic border zone after 3 days, peaked by 0.14% at day 5, and then decreased. In contrast, Ki-67 positive cells and dividing nuclei were limited in number in the non-ischemic area throughout all experiments. In conclusion, mitogenic cardiomyocytes are present in the adult rat heart following myocardial infarction, but were spatially and temporally restricted.

Animals↗
PubMed2004

A comparison between calcium channel blocking drugs with different potencies for T- and L-type channels in preventing atrial electrical remodeling.

Calcium overload plays a key role in the development of atrial electrical remodeling. The effect of an L-type Ca channel blocker in preventing this remodeling has been reported to be short lasting, partly due to down-regulation of this channel and persisting Ca entry through the T-type Ca channel. To prove if efonidipine, a dual L- and T-type Ca channel blocker exerts a greater effect than an L-type Ca channel blocker verapamil, 21 dogs underwent rapid atrial pacing at 400 bpm for 14 days, pretreatment with efonidipine in 7 (E), verapamil in 7 (V), and none in 7 (C). We measured the atrial effective refractory period (ERP) serially during 14 days of rapid pacing. In response to rapid pacing, ERP decreased progressively in C. In contrast, in E and V, ERP remained greater than ERP in C (P < 0.01) on days 2 through 7. However, on the 14th day, ERP in V decreased to the level seen in C, whereas ERP in E remained significantly longer than ERPs in C or V (P < 0.01). The blockade L-type Ca channel alone is not sufficient, but the addition of a T-type Ca channel blockade shows a more sustained effect to prevent atrial electrical remodeling.

Administration, Oral↗
PubMed2004

An evolutionarily conserved gene required for proper microtubule architecture in Caenorhabditis elegans.

Microtubules are involved in many cellular events during the cell cycle and also in a variety of early embryonic developmental processes. Their architecture and properties change dramatically during the cell cycle and are properly regulated. However, these regulatory mechanisms have not been fully elucidated. C05D11.3 gene of Caenorhabditis elegans encodes a low molecular weight protein that is evolutionarily conserved from yeasts to mammals. A mouse homolog of the C05D11.3 product, APACD (ATP binding protein associated with cell differentiation), contains a thioredoxin-like domain and P-loop, and is present in both the nucleus and the cytoplasm, showing often localization to centrosomes and midbody. In C. elegans, C05D11.3 is expressed throughout development with higher levels of expression in most cells of the nervous system and in vulva. C05D11.3 RNAi-treated embryos show apparent defects in pronuclear migration or nuclear-centrosome rotation, and exhibit little astral microtubules and defective small spindles. These results indicate that C05D11.3, an evolutionarily conserved gene, is essential for proper microtubule organization and function in C. elegans. This gene family may be a conserved regulator of microtubule dynamics and function.

Amino Acid Sequence↗
PubMed2004

Role of Herp in the endoplasmic reticulum stress response.

Application of differential display to cultured rat astrocytes allowed cloning of Herp cDNA. Although Herp was strongly induced by endoplasmic reticulum (ER) stress, it decayed rapidly consequent to proteasome-mediated degradation. To investigate the role of this molecule in terms of the stress response, Herp knockout cells were developed using F9 embryonic carcinoma cells. F9 Herp null cells were more vulnerable to ER stress compared with F9 wild-type cells. In the early period of ER stress (0-8 h after tunicamycin treatment), Herp null cells displayed enhanced ER stress signalling and stabilization of an endogenous ERAD substrate, compared with wild-type cells. In the intermediate period (8-20 h after tunicamycin treatment), Herp null cells displayed reduced ER stress signalling, whereas in the late period (20-40 h after tunicamycin treatment), Herp null cells manifested irreversible cellular changes that lead to apoptotic cell death. Transfection analysis revealed that the N-terminal region, including the ubiquitin-like domain of Herp, was required for the survival of F9 cells under ER stress. These results indicate that Herp is a short-lived Ub-like protein improving the balance of folding capacity and protein loads in the ER and plays crucial roles for the ER stress resistance in F9 cells.

Animals↗
PubMed2004

Endothelin-1 regulates cardiac sympathetic innervation in the rodent heart by controlling nerve growth factor expression.

The cardiac sympathetic nerve plays an important role in regulating cardiac function, and nerve growth factor (NGF) contributes to its development and maintenance. However, little is known about the molecular mechanisms that regulate NGF expression and sympathetic innervation of the heart. In an effort to identify regulators of NGF in cardiomyocytes, we found that endothelin-1 specifically upregulated NGF expression in primary cultured cardiomyocytes. Endothelin-1-induced NGF augmentation was mediated by the endothelin-A receptor, Gibetagamma, PKC, the Src family, EGFR, extracellular signal-regulated kinase, p38MAPK, activator protein-1, and the CCAAT/enhancer-binding protein delta element. Either conditioned medium or coculture with endothelin-1-stimulated cardiomyocytes caused NGF-mediated PC12 cell differentiation. NGF expression, cardiac sympathetic innervation, and norepinephrine concentration were specifically reduced in endothelin-1-deficient mouse hearts, but not in angiotensinogen-deficient mice. In endothelin-1-deficient mice the sympathetic stellate ganglia exhibited excess apoptosis and displayed loss of neurons at the late embryonic stage. Furthermore, cardiac-specific overexpression of NGF in endothelin-1-deficient mice overcame the reduced sympathetic innervation and loss of stellate ganglia neurons. These findings indicate that endothelin-1 regulates NGF expression in cardiomyocytes and plays a critical role in sympathetic innervation of the heart.

Animals↗
PubMed2004

Stenting after directional coronary atherectomy compared with directional coronary atherectomy alone and stenting alone: a serial intravascular ultrasound study.

BACKGROUND: Directional coronary atherectomy prior to stent implantation (DCA-stent) is expected to be an effective approach to reduce restenosis. The purpose of this study was to determine whether DCA-stent has advantages over DCA alone or stenting alone using serial intravascular ultrasound (IVUS). METHODS AND RESULTS: Serial (pre-, post- and follow-up) IVUS was performed in 187 native coronary lesions treated with each of the 3 strategies. External elastic membrane cross-sectional area (CSA), lumen CSA and plaque CSA were measured. Baseline characteristics were similar. Postprocedural lumen CSA was largest after DCA-stent (11.2+/-2.7 mm2) and DCA (10.8+/-2.5 mm2) than stenting alone (9.0+/-2.9 mm2) (p<0.0005). Follow-up lumen loss was similar. As a result, follow-up lumen CSA was largest after DCA-stent (DCA-stent: 9.1+/-3.4 mm2, DCA: 7.8+/-4.2 mm2, stent: 6.3+/-2.6 mm2, p<0.0005). There was a trend toward a lower rate of restenosis with DCA-stent (DCA-stent, 12.5%; DCA, 18.3%; stent, 18.8%; p=0.57). CONCLUSIONS: DCA-stent is superior to both DCA alone and stent alone in terms of the ability to gain a larger lumen as assessed by IVUS.

Aged↗
PubMed2004

Oral verapamil attenuates the progression of pacing-induced electrical and mechanical remodeling of the atrium.

BACKGROUND: Calcium overload plays a major role in the development of electrical and mechanical remodeling during atrial fibrillation, but the potential of verapamil, a Ca blocker, for preventing atrial electrical remodeling remains controversial. METHODS AND RESULTS: Pacing and recording electrodes were sutured to the right atrium in 16 dogs. After a 5-day recovery period, rapid atrial pacing at 400 ppm was initiated in 8 dogs (control group). In the remaining 8 dogs, oral administration of verapamil (8 mg/kg per day) was started 1 week before the initiation of rapid pacing (verapamil group). On the day before and at 2, 7, 14 days after rapid pacing, electrophysiological (EP) and transesophageal echocardiographic (TEE) studies were performed under autonomic blockade. In response to rapid pacing, EP and TEE parameters changed progressively in the control group (p<0.05 vs day 0), whereas in the verapamil group, no significant changes in the various parameters were observed for the first 7 days. However, verapamil failed to prevent progression of both types of remodeling after 14 days of pacing. CONCLUSION: Verapamil can attenuate the progression of electrical and mechanical remodeling of the atrium for at least 7 days.

Administration, Oral↗
PubMed2004

Prominent expression of spinocerebellar ataxia type-1 (SCA1) gene encoding ataxin-1 in LH-producing cells, LbetaT2.

The LH-producing cell line, LbetaT2, and non LH-producing cell line, alphaT3-1 cells, established from a pituitary tumor, were employed for cDNA subtraction cloning to identify genes with expression unique to LH producing cells. Several cDNAs that code for known as well as for many unidentified clones were discovered. Most clones were the spinocerebellar ataxia type-1 (SCA1) gene encoding ataxin-1, the abnormality of which causes neurodegeneration and loss of cerebellar Purkinje cells. We examined whether the expression of SCA1 gene in LbetaT2 cells is related to hormone production. We also compared the expression of SCA1 with that in various other pituitary tumor derived cell lines, and confirmed the prominent expression of SCA1 in LbetaT2 cells. The effect of gonadal factor(s) for SCA1 gene expression was examined. The expression level in female rats was low and did not change during the estrus cycle, but increased significantly after ovariectomy and did not return to the normal level under low and high doses of estrogen. In the male pituitary SCA1 gene expression increased markedly after castration and was not decreased by estrogen or testosterone. The Ontogeny of SCA1 gene expression was investigated in porcine fetal and postnatal pituitaries and revealed biphasic and sexually dimorphic expression. Transient expression of SCA1 gene was observed at fetal day 50 and 65 in males and day 40 in females, followed by a decline and increased expression before birth in both genders. Thus the expression of SCA1 gene is prominent in LH-producing cells and is not under direct control of gonadal factor(s) in both genders. In addition to the variable expression of SCA1 gene during the fetus period, the present results provide a novel aspect to the understanding of Boucher-Neuhauser syndrome (Ataxia Hypogonadism Choroidal Dystrophy).

Androgens↗
PubMed2004

Association between serum C-reactive protein elevation and left ventricular thrombus formation after first anterior myocardial infarction.

STUDY OBJECTIVES: Most left ventricular (LV) thrombi that occur after acute myocardial infarction (AMI) are formed within 2 weeks, when inflammatory cells have infiltrated into the necrotic myocardium. Inflammatory changes on the endocardial surface may induce platelet deposition and fibrin net formation through interaction with proinflammatory cytokines. We sought to determine the significance of the inflammatory response reflected by serum C-reactive protein (CRP) elevation in LV thrombus formation after AMI. DESIGN: We examined 160 patients with first anterior AMI. Peak serum creatine kinase (CK) and CRP levels were determined by serial measurements. Echocardiography was performed 10 to 14 days after the onset. We assessed the association between the elevation of serum CRP levels and LV thrombus formation after AMI. RESULTS: LV thrombus was observed in 13 patients (8%). There was no difference in age, sex, coronary risk factors, preinfarction angina, use of revascularization therapy and anticoagulant therapy, platelet count, and fibrinogen level on hospital admission between the two groups. The mean (+/- SD) peak serum CRP level was markedly increased in patients with LV thrombus compared to those without (18.0 +/- 12.6 vs 9.4 +/- 8.1 mg/dL; p = 0.001), despite their having similar peak CK levels. Multivariate analysis showed that a peak CRP level of > or =20 mg/dL was an independent predictor of thrombus formation (relative risk, 4.82; p = 0.037) among variables including older age (> or =60 years old), peak CK level (> or =3,000 IU/L), and peak WBC count (> or =12,000 cells/ microL). CONCLUSION: A greater elevation of serum CRP level was associated with a higher incidence of LV thrombus after AMI, suggesting an important role of the inflammatory response in mural thrombus formation.

Aged↗
PubMed2004

Effect of cilostazol, a phosphodiesterase inhibitor, on carotid IMT in Japanese type 2 diabetic patients.

The aim of this study was to investigate the effect of cilostazol, a cAMP phosphodiesterase inhibitor, on carotid artery intima-media thickness (IMT) and on the incidence of cardiovascular events in Japanese subjects with type 2 diabetes. A total of 62 type 2 diabetic subjects were allocated equally to the cilostazol treatment group (n = 31) and the control group (n = 31). Carotid IMT was evaluated before and after treatment using B-mode ultrasonography. After the study period (mean +/- SD: 2.6 +/- 0.17 years), carotid IMT showed a significantly greater increase in the control group than in the cilostazol group (0.12 +/- 0.14 mm vs. 0.04 +/- 0.02 mm, p < 0.05). In the control group, 1 out of 31 patients suffered from symptomatic cerebral infarction and 1 had angina pectoris during the observation period. On the other hand, no subject in the cilostazol group developed cardiovascular events during the study period. At baseline, the diabetic patients given cilostazol had a significantly lower HbA1c level than the control subjects, but the other atherosclerotic risk factors (BMI, blood pressure, and serum lipids) and the duration of diabetes did not differ between the two groups. These results indicate that cilostazol therapy can attenuate the increase of carotid artery IMT in Japanese subjects with type 2 diabetes.

Aged↗
PubMed2004

Marked improvement with sildenafil in a patient with primary pulmonary hypertension unresponsive to epoprostenol.

We report a 48-year-old woman with right heart failure due to primary pulmonary hypertension. Continuous infusion of epoprostenol (prostaglandin I2) for 1.5 years failed to control her condition, but she was later successfully treated with additional sildenafil for a few months. Her mean pulmonary artery pressure was originally 57 mmHg, increased to 62 mmHg with epoprostenol, and decreased to 45 mmHg with sildenafil. Additional sildenafil may be an effective and life-saving agent in patients with primary pulmonary hypertension who show a poor response to epoprostenol, which is considered to be very powerful medical treatment for the disease.

Antihypertensive Agents↗
PubMed2003

Usefulness of residual percent plaque area after percutaneous coronary intervention in predicting peristent positive remodeling.

The aim of this study was to determine whether a stented coronary artery might be positively remodeled, which factors predict this phenomenon, and whether positive remodeling has an association with late outcome. The study population consisted of 230 lesions in 230 patients who received bare-metal stents. We performed intravascular ultrasound analyses before and after the procedure and at follow-up. An artery was defined as positively remodeled if the ratio of follow-up to postvessel area was > or =1.1. The following indexes were calculated and defined: (1) late loss = postluminal area - follow-up luminal area; (2) percent plaque area = ([vessel area - luminal area]/vessel area x 100), (3) Delta% plaque area = follow-up percent plaque area - postprocedure percent plaque area. Although late loss in the positively remodeled group was significantly smaller than that in the nonremodeled group (p<0.05), d% plaque area in the former group was significantly larger than that in the latter group (p<0.05). The rate of restenosis in the positive remodeling group (16.4%) was significantly lower than that in the nonremodeling group (28.2%) (p<0.05). In multivariate analysis, postprocedure percent plaque area was the only powerful independent predictor for peristent positive remodeling and was inversely associated with this phenomenon in both groups (odds ratio 0.944, 95% confidence interval 0.914 to 0.975, p=0.0004). This study indicates that postprocedure percent plaque area could predict the occurrence of peristent positive remodeling at follow-up and that this phenomenon might influence late outcome.

Angioplasty, Balloon, Coronary↗