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Biomedical subjects

Toru Suzuki

Publications and source records attributed to Toru Suzuki.

18 recordsLinked to original sources
PubMed2003

Clinical profiles and outcomes of acute type B aortic dissection in the current era: lessons from the International Registry of Aortic Dissection (IRAD).

BACKGROUND: Clinical profiles and outcomes of patients with acute type B aortic dissection have not been evaluated in the current era. METHODS AND RESULTS: Accordingly, we analyzed 384 patients (65+/-13 years, males 71%) with acute type B aortic dissection enrolled in the International Registry of Acute Aortic Dissection (IRAD). A majority of patients had hypertension and presented with acute chest/back pain. Only one-half showed abnormal findings on chest radiograph, and almost all patients had computerized tomography (CT), transesophageal echocardiography, magnetic resonance imaging (MRI), and/or aortogram to confirm the diagnosis. In-hospital mortality was 13% with most deaths occurring within the first week. Factors associated with increased in-hospital mortality on univariate analysis were hypotension/shock, widened mediastinum, periaortic hematoma, excessively dilated aorta (>or=6 cm), in-hospital complications of coma/altered consciousness, mesenteric/limb ischemia, acute renal failure, and surgical management (all P<0.05). A risk prediction model with control for age and gender showed hypotension/shock (odds ratio [OR] 23.8, P<0.0001), absence of chest/back pain on presentation (OR 3.5, P=0.01), and branch vessel involvement (OR 2.9, P=0.02), collectively named 'the deadly triad' to be independent predictors of in-hospital death. CONCLUSIONS: Our study provides insight into current-day profiles and outcomes of acute type B aortic dissection. Factors associated with increased in-hospital mortality ("the deadly triad") should be identified and taken into consideration for risk stratification and decision-making.

Aged↗
PubMed2003

Functional interaction of the DNA-binding transcription factor Sp1 through its DNA-binding domain with the histone chaperone TAF-I.

Transcription involves molecular interactions between general and regulatory transcription factors with further regulation by protein-protein interactions (e.g. transcriptional cofactors). Here we describe functional interaction between DNA-binding transcription factor and histone chaperone. Affinity purification of factors interacting with the DNA-binding domain of the transcription factor Sp1 showed Sp1 to interact with the histone chaperone TAF-I, both alpha and beta isoforms. This interaction was specific as Sp1 did not interact with another histone chaperone CIA nor did other tested DNA-binding regulatory factors (MyoD, NFkappaB, p53) interact with TAF-I. Interaction of Sp1 and TAF-I occurs both in vitro and in vivo. Interaction with TAF-I results in inhibition of DNA-binding, and also likely as a result of such, inhibition of promoter activation by Sp1. Collectively, we describe interaction between DNA-binding transcription factor and histone chaperone which results in negative regulation of the former. This novel regulatory interaction advances our understanding of the mechanisms of eukaryotic transcription through DNA-binding regulatory transcription factors by protein-protein interactions, and also shows the DNA-binding domain to mediate important regulatory interactions.

Amino Acid Sequence↗
PubMed2003

Mice lacking a transcriptional corepressor Tob are predisposed to cancer.

tob is a member of antiproliferative family genes. Mice lacking tob are prone to spontaneous formation of tumors. The occurrence rate of diethylnitrosamine-induced liver tumors is higher in tob(-/-) mice than in wild-type mice. tob(-/-)p53(-/-) mice show accelerated tumor formation in comparison with single null mice. Expression of cyclin D1 mRNA is increased in the absence of Tob and is reduced by Tob. Tob acts as a transcriptional corepressor and suppresses the cyclin D1 promoter activity through an interaction with histone deacetylase. Levels of tob mRNA are often decreased in human cancers, implicating tob in cancer development.

Animals↗
PubMed2003

Neoendothelialization after peripheral blood stem cell transplantation in humans: a case report of a Tokaimura nuclear accident victim.

OBJECTIVES: Neoendothelialization by circulating endothelial progenitor cells has been a topic of recent research. The extent and scale of this process in humans is not well understood. We examined the extent of neoendothelialization of the aorta and peripheral arteries in the case of a patient who underwent peripheral blood stem cell transplantation for acute radiation syndrome. METHODS: Human tissue samples from the aorta and peripheral arteries were obtained at autopsy. Endothelial cells were isolated, confirmed by von Willebrand factor immunostaining, and then subjected to fluorescent in situ hybridization analysis using X- and Y-chromosome specific probes to examine neoendothelialization by donor cells as possible in this case in which the donor and recipient were of different genders. RESULTS: The aorta showed almost 25% of all endothelial cells to be replaced by donor-origin endothelial cells. The peripheral arteries were also replaced but to a lesser extent. DISCUSSION: The present study provides evidence that peripheral blood is a source of endothelial progenitor cells in humans. Neoendothelialization of the aorta occurs to a significant extent under certain conditions suggesting the potential for exploitation of therapeutic neovascularization by transplantation of circulating endothelial progenitor cells.

Adult↗
PubMed2002

Resistance to neointimal hyperplasia and fatty streak formation in mice with adrenomedullin overexpression.

OBJECTIVE: Several in vitro studies have implicated that adrenomedullin (AM) plays an important role in the pathogenesis of vascular injury and fatty streak formation. To test this possibility in vivo, we evaluated 2 experimental models using transgenic mice overexpressing AM in a vessel-selective manner (AMTg mice). METHODS AND RESULTS: Placement of a periarterial cuff on femoral arteries resulted in neointimal formation at 2 to 4 weeks to a lesser extent in AMTg mice than in their wild-type littermates (at 28 days, intima/media area ratio 0.45+/-0.14 versus 1.31+/-0.41, respectively; P<0.001). This vasculoprotective effect observed in AMTg mice was inhibited by N(omega)-nitro-L-arginine methyl ester. We further examined the effect of AM on hypercholesterolemia-induced fatty streak formation by crossing AMTg mice with apolipoprotein E knockout mice (ApoEKO mice). The extent of the formation of fatty streak lesions was significantly less in ApoEKO/AMTg mice than in ApoEKO mice (percent lesion area 12.0+/-3.9% versus 15.8+/-2.8%, respectively; P<0.05). Moreover, endothelium-dependent vasodilatation as indicative of NO production was superior in AMTg/ApoEKO mice compared with ApoEKO mice. CONCLUSIONS: Taken together, our data demonstrated that AM possesses a vasculoprotective effect in vivo, which is at least partially mediated by NO.

Adipose Tissue↗
PubMed2002

Krüppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling.

We recently isolated a Krüppel-like zinc-finger transcription factor 5 (KLF5; also known as BTEB2 and IKLF), which is markedly induced in activated vascular smooth-muscle cells and fibroblasts. Here we describe our analysis of the in vivo function of KLF5 using heterozygous KLF5-knockout mice (Klf5(+/-)). In response to external stress, Klf5(+/-) mice showed diminished levels of arterial-wall thickening, angiogenesis, cardiac hypertrophy and interstitial fibrosis. Also, angiotensin II induced expression of KLF5, which in turn activated platelet-derived growth factor-A (PDGF-A) and transforming growth factor-beta (TGF-beta) expression. In addition, we determined that KLF5 interacted with the retinoic-acid receptor (RAR), that synthetic RAR ligands modulated KLF5 transcriptional activity, and that in vivo administration of RAR ligands affected stress responses in the cardiovascular system in a KLF5-dependent manner. KLF5 thus seems to be a key element linking external stress and cardiovascular remodeling.

Angiotensin II↗
PubMed2002

Phosphorylation of three regulatory serines of Tob by Erk1 and Erk2 is required for Ras-mediated cell proliferation and transformation.

tob is a member of an emerging family of genes with antiproliferative function. Tob is rapidly phosphorylated at Ser 152, Ser 154, and Ser 164 by Erk1 and Erk2 upon growth-factor stimulation. Oncogenic Ras-induced transformation and growth-factor-induced cell proliferation are efficiently suppressed by mutant Tob that carries alanines but not glutamates, mimicking phosphoserines, at these sites. Wild-type Tob inhibits cell growth when the three serine residues are not phosphorylated but is less inhibitory when the serines are phosphorylated. Because growth of Rb-deficient cells was not affected by Tob, Tob appears to function upstream of Rb. Intriguingly, cyclin D1 expression is elevated in serum-starved tob(-/-) cells. Reintroduction of wild-type Tob and mutant Tob with serine-to-alanine but not to glutamate mutations on the Erk phosphorylation sites in these cells restores the suppression of cyclin D1 expression. Finally, the S-phase population was significantly increased in serum-starved tob(-/-) cells as compared with that in wild-type cells. Thus, Tob inhibits cell growth by suppressing cyclin D1 expression, which is canceled by Erk1- and Erk2-mediated Tob phosphorylation. We propose that Tob is critically involved in the control of early G(1) progression.

3T3 Cells↗
PubMed2002

Fractal analysis of ice crystals in frozen food.

Fractal analysis of the morphology of ice crystal particles in frozen food was attempted for frozen soybean curd (tofu). From a microscopic image analysis of the ice crystal particles, it was found that the perimeter of the ice crystal particles could be recognized as a fractal. Effects of the storage time and storage temperature on the fractal dimension (d(p)) of the perimeter of the ice crystal particles were also investigated. As storage time was increased, the d(p) value tended to decrease. When the storage temperature was increased, the value of d(p) decreased more rapidly. The changes corresponded to the visual observation of the shape change for the ice crystal particles during storage reported by many researchers, suggesting that the fractal dimension d(p) could be used as a quantitative indicator reflecting the surface roughness of ice crystal particles.

Crystallization↗
PubMed2002

Regulation of angiogenesis by the aging suppressor gene klotho.

Advanced age is a major risk factor of peripheral artery disease. We examined the effects of the aging-suppressor gene klotho on angiogenesis in response to ischemia by introducing ischemic hindlimb model in mice heterozygously deficient for the klotho gene and in wild type mice. Blood flow recovery as assessed by laser doppler perfusion imaging and angiogenesis as assessed by density of PECAM-1/CD31-positive positive capillaries were markedly impaired in mice heterozygously deficient for the klotho gene (both <0.05). Our findings show that the aging-suppressor gene klotho affects angiogenesis and the possibility that age-related impairment of angiogenesis might be regulated by the klotho gene. Our results present a new possibility of therapeutic angiogenesis for patients of advanced age.

Aging↗
PubMed2002

Predicting death in patients with acute type a aortic dissection.

BACKGROUND: Given the high mortality rates in patients with type A aortic dissection, predictive tools to identify patients at increased risk of death are needed to assist clinicians for optimal treatment. METHODS AND RESULTS: Accordingly, we evaluated 547 patients with this diagnosis enrolled in the International Registry of Acute Aortic Dissection (IRAD) between January 1996 and December 1999. Univariate testing followed by multivariate logistic regression analysis was performed to identify independent predictors of death. In-hospital mortality rate was 32.5% in type A dissection patients. In-hospital complications (neurological deficits, altered mental status, myocardial or mesenteric ischemia, kidney failure, hypotension, cardiac tamponade, and limb ischemia) were increased in patients who died compared with survivors (P<0.05 for all). Logistic regression identified the following presenting variables as predictors of death: age > or =70 years (OR, 1.70; 95% CI, 1.05 to 2.77; P=0.03), abrupt onset of chest pain (OR 2.60; 95% CI, 1.22 to 5.54; P=0.01), hypotension/shock/tamponade (OR, 2.97; 95% CI, 1.83 to 4.81; P<0.0001), kidney failure (OR, 4.77; 95% CI, 1.80 to 12.6; P=0.002), pulse deficit (OR, 2.03; 95% CI, 1.25 to 3.29, P=0.004), and abnormal ECG (OR, 1.77; 95% CI, 1.06 to 2.95; P=0.03) (area under receiver operating curve, 0.74; Hosmer-Lemeshow statistic, P=0.75). CONCLUSIONS: The in-hospital mortality rate in acute type A aortic dissection is high and can be predicted with the use of a clinical model incorporated in a simple risk prediction tool. This tool can be used to educate patients with dissection about their predicted risk and in clinical research for risk adjustment while comparing outcomes of different therapies.

Aged↗
PubMed2002

Diagnostic implications of circulating oxidized low density lipoprotein levels as a biochemical risk marker of coronary artery disease.

OBJECTIVES: To examine the diagnostic performance of circulating oxidized low density lipoprotein levels as a biochemical risk marker of coronary heart disease. DESIGN AND METHODS: 361 patients with coronary artery disease and 710 healthy volunteers as normal controls were examined. Receiver-operating characteristics curve analysis in addition to statistical analysis (univariate, multivariate) were done to determine the usefulness of the assay. RESULTS: Patients with coronary artery disease showed significantly elevated circulating oxidized low density lipoprotein levels. Males less than 70 years of age showed a significant association between oxidized low density lipoprotein levels and coronary artery disease. Receiver-operating characteristics curve analysis showed superior performance (e.g., sensitivity, specificity) of oxidized low density lipoprotein as a diagnostic marker of coronary artery disease as compared against other lipid markers (total cholesterol, triglyceride, high density lipoprotein, lipoprotein (a), and total cholesterol to high density lipoprotein ratio) with optimal performance in younger males. CONCLUSIONS: Oxidized low density lipoprotein levels may be a promising biochemical risk marker of atherosclerotic disease, especially in young males.

Adult↗
PubMed2002

Factors affecting the uptake of DMSO by the eggs and embryos of medaka, Oryzias latipes.

High performance liquid chromatography (HPLC) was used to assess the uptake dynamics of the cryoprotectant DMSO by intact unfertilized eggs (stage 0), 8-cell (stage 5) and eyed embryos (stage 30) of medaka, Oryzias latipes, the relation of the internal concentration (Cin) of DMSO with fertilization and survival rates, and the effects of several factors on these processes. The factors examined were: cryoprotectant concentration (0.6, 1.2, 1.9 and 2.5 M), impregnation time (1, 3, 5, 10, 15 and 20 min), temperature (0, 5 and 20 degrees C), hydrostatic pressure (0 and 50 atm), and the osmotic conditions of the materials (normal or partially dehydrated). Cryoprotectant permeation, estimated from the initial rates of DMSO uptake, was higher in embryos than in eggs and increased with embryonic development; however, the DMSO Cin in eyed embryos reached a plateau at 1-5 min and could not be increased by prolonging impregnation. The highest fertilization and survival rates for any given DMSO Cin were obtained with high concentrations and short times of impregnation rather than low concentrations and long impregnation times. Application of hydrostatic pressure (50 atm) and exposure for 3 min to a 1 M trehalose solution prior to impregnation induced a substantial increase in the DMSO Cin of 8-cell embryos in comparison to untreated controls with no significant effect on survival. Hydrostatic pressure also promoted DMSO uptake in unfertilized eggs, but with rapid loss of viability, and was ineffective in eyed embryos. The uptake of DMSO and its toxicity to 8-cell embryos were directly proportional to the temperature of impregnation. The results of this study reveal important interactions between cryoprotectant concentration, impregnation time and the developmental stage (or type) of the materials and provide evidence that hydrostatic pressure, temperature of impregnation and the osmotic conditions of the materials can be manipulated to increase the uptake of cryoprotectant by fish eggs and embryos.

Animals↗
PubMed2002

Transmeatal low-power laser irradiation for tinnitus.

OBJECTIVE: To evaluate effectiveness of 60-mW laser irradiation in the treatment of tinnitus. STUDY DESIGN: Prospective, randomized double-blind study. METHODS: This investigation included 68 ears in 45 patients with disabling unilateral or bilateral tinnitus. The active or placebo laser treatment was administered transmeatally once a week for 6 minutes. Laser irradiation was performed four times during a 4-week period. A questionnaire was administered to evaluate the loudness, duration, quality, and annoyance of tinnitus before and after irradiation. The loudness and pitch match for tinnitus were obtained, and distortion product otoacoustic emissions were also examined. RESULTS: No significant difference was observed between the active and placebo laser groups with regard to outcome of loudness, duration, quality, and annoyance of tinnitus. In one patient who received active laser treatment, acute hearing deterioration occurred after the third irradiation. CONCLUSION: Transmeatal low-power laser irradiation with 60 mW is not effective for the treatment of tinnitus.

Adult↗
PubMed2002

In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage.

The klotho gene, originally identified by insertional mutagenesis in mice, suppresses the expression of multiple aging-associated phenotypes. This gene is predominantly expressed in the kidney. Recent studies have shown that expression of renal klotho gene is regulated in animal models of metabolic diseases and in humans with chronic renal failure. However, little is known about the mechanisms and the physiological relevance of the regulation of the expression of the klotho gene in the kidney in some diseased conditions. In the present study, we first investigated the role of angiotensin II in the regulation of renal klotho gene expression. Long-term infusion of angiotensin II downregulated renal klotho gene expression at both the mRNA and protein levels. This angiotensin II-induced renal klotho downregulation was an angiotensin type 1 receptor-dependent but pressor-independent event. Adenovirus harboring mouse klotho gene (ad-klotho, 3.3x10(10) plaque forming units) was also intravenously administered immediately before starting angiotensin II infusion in some rats. This resulted in a robust induction of Klotho protein in the liver at day 4, which was still detectable 14 days after the gene transfer. Ad-klotho gene transfer, but not ad-lacZ gene transfer, caused an improvement of creatinine clearance, decrease in urinary protein excretion, and amelioration of histologically demonstrated tubulointerstitial damage induced by angiotensin II administration. Our data suggest that downregulation of the renal klotho gene may have an aggravative role in the development of renal damage induced by angiotensin II, and that induction of the klotho gene may have therapeutic possibilities in treating angiotensin II-induced end organ damage.

Angiotensin II↗
PubMed2000

Serum levels of smooth muscle heavy-chain myosin in patients with ectopic pregnancy.

STUDY OBJECTIVE: Previous studies have suggested that serum markers of smooth muscle destruction have utility in predicting ectopic pregnancy. Our goal was to determine whether a novel marker of muscle destruction, smooth muscle heavy-chain myosin (SMHC), is elevated in the serum of patients with ectopic pregnancy. METHODS: We conducted a prospective cohort study, with consecutive enrollment, of all women in the first trimester of pregnancy who presented to our urban emergency department with complaints of lower abdominal pain with or without vaginal bleeding. Patients were excluded if there was a history of recent surgery or major trauma. Means were compared using 2-tailed Student's t test with P values less than.05 set for significance. Data analysis included calculation of receiver operating characteristic (ROC), 95% confidence intervals (CIs), and a regression model. RESULTS: A total of 175 patients were enrolled; ectopic pregnancy was diagnosed in 29, and 146 had other diagnoses. Patients with ectopic pregnancy had a mean serum SMHC concentration of 2.53 ng/dL (95% CI 1.84 to 3.22), whereas those in the non-ectopic pregnancy group had a mean concentration of 1.41 ng/dL (95% CI 1.23 to 1.60; P <.0001). ROC analysis demonstrated an area under the curve of 0.72 (95% CI 0.65 to 0.79). Regression analysis to examine confounders in each group analyzed the effects of race, maternal age, estimated gestational age, and serum levels of human chorionic gonadotropin beta-subunit. Our analysis identified only a positive correlation between estimated gestational age and SMHC in the non-ectopic pregnancy group. CONCLUSION: There is a statistically significant elevation of serum SMHC levels in tubal pregnancy, although our data suggest that the assay has limited clinical utility as a lone marker for ectopic pregnancy. Further investigation is needed to determine whether the assay has a role as an adjunct in the evaluation of suspected ectopic pregnancy.

Abdominal Pain↗