Biomedical subjects

Toru Suzuki

Publications and source records attributed to Toru Suzuki.

At least 37 records · Page 2Linked to original sources

PubMed2005

Acute aortic dissection presenting with primarily abdominal pain: a rare manifestation of a deadly disease.

The objective of this study was to determine the morbidity and mortality of patients with acute thoracic aortic dissections who present primarily with abdominal pain. Nine hundred ninety-two patients (mean age, 62.1 years +/- 14.1; 68% male) encountered from 1996 to 2001 with acute thoracic aortic dissections from the International Registry of acute Aortic Dissection were studied. Patient demographics, presenting symptoms, signs of aortic dissection, aortic pathology, and mortality were compared in patients presenting primarily with abdominal pain (group I, 46 patients, 4.6%) versus all others (group II). Demographics were similar between the two groups. When signs of aortic dissection were examined, 63% of patients in group I presented with hypertension compared to only 47% of patients in group II (p = 0.04). Patients in group I were less likely to present with evidence of end-organ malperfusion. Importantly, mortality in patients with a type B dissection, specifically following surgery for the dissection, was significantly increased in patients who presented primarily with abdominal pain (group I, 28% mortality vs. group II, 10.2% mortality; p = 0.02). This study documented increased mortality in patients with acute thoracic aortic dissections who present primarily with abdominal pain, underscoring the importance of maintaining a high index of suspicion for an aortic dissection in patients who have appropriate risk factors.

Abdominal Pain↗

PubMed2005

Comparative investigation by two analytical approaches of enthalpy relaxation for glassy glucose, sucrose, maltose, and trehalose.

PURPOSE: In an effort to understand the stability of glassy sugars such as glucose, sucrose, maltose, and trehalose, the molecular mobility below the glass transition temperature (Tg) was investigated by an enthalpy relaxation measurement with differential scanning calorimetry (DSC). METHODS: The glassy sample was aged over several days at (Tg - 10) K to (Tg - 30) K, before a DSC heating scan was taken. The relaxed enthalpy (deltaHrelax) was estimated from the endothermic peak area. The enthalpy relaxation time was analyzed from the time course of deltaHrelax using two different approaches; Kohlrausch-Williams-Watts (KWW) and extended Adam-Gibbs (exAG). RESULTS: TauKWW, which is defined as the mean average enthalpy relaxation time in a distribution, and tau(eff)0 and tau(eff)infinity, which correspond to the enthalpy relaxation time of the initial minimum and final maximum cooperative rearrangement region, were estimated by KWW and exAG, respectively. And three activation energies for enthalpy relaxation were calculated from the Arrhenius plot. CONCLUSIONS: Although these deltaEs originated from different theoretical backgrounds, almost the same trend was observed for a comparison of the values of the four sugars. The finding that the deltaEs of glassy trehalose were the largest among the four sugars may support the reason that glassy trehalose is an effective stabilizer.

Calorimetry, Differential Scanning↗

PubMed2005

Contemporary results of surgery in acute type A aortic dissection: The International Registry of Acute Aortic Dissection experience.

BACKGROUND: Surgical mortality for acute type A aortic dissection reported in different experiences from single centers or surgeons varies from 7% to 30%. The International Registry of Acute Aortic Dissection, collecting patients from 18 referral centers worldwide, identifies a preoperative risk stratification scheme and a real average surgical mortality for acute type A aortic dissection in the current era. METHODS: A comprehensive analysis was completed of 290 clinical variables and their relationship to surgical outcomes in 526 of 1032 patients enrolled in the International Registry of Acute Aortic Dissection from 1996 through 2001. Extracted cases, categorized according to risk profile, were defined as unstable (group I) in the presence of cardiac tamponade; shock; congestive heart failure; cerebrovascular accident; stroke; coma; myocardial ischemia, infarction, or both; electrocardiograms with new Q waves or ST elevation; acute renal failure; or mesenteric ischemia-infarction at the time of the operation. Outside of an unstable condition, patients were categorized as stable (group II). RESULTS: The overall in-hospital mortality was 25.1%. Mortality in group I was 31.4% compared with 16.7% in group II ( P < .001). Independent preoperative predictors of operative mortality were history of aortic valve replacement (odds ratio = 3.12), migrating chest pain (odds ratio = 2.77), hypotension as sign of acute type A aortic dissection (odds ratio = 1.95), shock or tamponade (odds ratio = 2.69), preoperative cardiac tamponade (odds ratio = 2.22), and preoperative limb ischemia (odds ratio = 2.10). CONCLUSIONS: The International Registry of Acute Aortic Dissection experience confirms that patient selection plays an important role in determining surgical outcomes in patients with acute type A aortic dissection. Knowledge of significant risk factors for operative mortality can contribute to better management and a more defined risk assessment in patients affected by acute type A aortic dissection.

Acute Disease↗

PubMed2005

Transcriptional regulation at the chromatin level in the cardiovasculature through protein-protein interactions and chemical modifications.

Transcriptional regulation in eukaryotes requires an understanding of the regulation of the chromatin structure. Chromatin is the eukaryotic-specific packaging/compaction of DNA with nucleosomal histones. This present review discusses recent advancements made in the field of chromatin-associated transcriptional regulation and their implications to the cardiovasculature.

Cardiovascular Physiological Phenomena↗

PubMed2005

Development of a novel type of shoe to improve the efficiency of knee-ankle-foot orthoses with a medial single hip joint (Primewalk orthoses): a novel type of shoe for Primewalk orthosis.

The purpose of the study was to develop and evaluate a new heel cushion in shoes for use with knee-ankle-foot orthoses having a medial single hip joint (Primewalk orthoses) in order to improve walking velocity and efficiency. Primewalk orthoses and shoes were made for a 24-year-old man having paraplegia with flaccid paresis (level T-7; grade A, ASIA impairment scale) of 2 years' duration. Walking exercises were assigned. Shoes were modified with the sole made of hard rubber and the addition of soft rubber heel cushions. The walking speed, centre of foot pressure during walking, and ground reaction force were evaluated. The patient also subjectively assessed the devices. The modifications to the shoes resulted in a 1.94-fold increase in walking speed (8.6 to 16.7 m/min), a 1.87-fold increase in step length (16.7 to 31.3 cm) and a 54.8% decrease in the physiological cost index (7.7 to 3.48 beats/min). The centre of foot pressure during walking was found to deviate towards the lateral margin of the foot. The horizontal rotation of the pelvis increased simultaneously. The patient reported increased amplitude of flail motion of the trunk and decreased burden to the upper limbs. It was concluded that the modified new heel cushion of the shoe provided freedom to the lower legs and thereby increased walking efficiency.

Adult↗

PubMed2005

Interaction of anti-proliferative protein Tob with poly(A)-binding protein and inducible poly(A)-binding protein: implication of Tob in translational control.

Tob is a member of an emerging family of anti-proliferative proteins that suppress cell growth when over-expressed. tob mRNA is highly expressed in anergic T cells and over-expression of Tob suppresses transcription of interleukin-2 (IL-2) through its interaction with Smads. Here, we identified two types of cDNA clones coding for poly(A)-binding protein (PABP) and inducible PABP (iPABP) by screening an expression cDNA library with the GST-Tob probe. Co-immunoprecipitation and GST-pull down experiments showed that Tob associated with the carboxyl-terminal region of iPABP. We then found that iPABP, like PABP, was involved in regulation of translation: iPABP enhanced translation of IL-2 mRNA in vitro. The enhanced translation of IL-2 mRNA required the 3'UTR and poly(A) sequences. Tob abrogated the enhancement of translation through its interaction with carboxyl-terminal region of iPABP in vitro. Consistently, over-expression of Tob in NIH3T3 cells, in which exogenous iPABP was stably expressed, resulted in suppression of IL-2 production from the simultaneously transfected IL-2 expression plasmid. Finally, Tob, whose expression was induced by anergic stimulation, was co-immunoprecipitated with iPABP in human T cells. These findings suggest that Tob is involved in the translational suppression of IL-2 mRNA in anergic T cells through its interaction with iPABP.

3' Untranslated Regions↗

PubMed2004

Nuclear localization of Tob is important for regulation of its antiproliferative activity.

TOB: is a member of an antiproliferative gene family that includes btg1, pc3/tis21/btg2, pc3b, ana/btg3, and tob2. Exogenous overexpression of the family proteins suppresses cell proliferation. These proteins participate in transcriptional regulation of several genes. Here, we show that Tob is a nuclear protein that is imported into the nucleus through a nuclear localization signal (NLS)-mediated mechanism. Mutation in the NLS sequence of Tob affects its nuclear localization and impairs antiproliferative activity. Additionally, Tob contains a nuclear export signal (NES). In oncogenic ErbB2-transformed cells, nuclear export of Tob is facilitated by NES-mediated mechanism, resulting in decrease of its antiproliferative activity. These results indicate that regulation of nuclear localization of Tob is important for its antiproliferative activity.

Animals↗

PubMed2004

Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta.

Spermatogenesis is a complex process that involves cooperation of germ cells and testicular somatic cells. Various genetic disorders lead to impaired spermatogenesis, defective sperm function and male infertility. Here we show that Cnot7(-/-) males are sterile owing to oligo-astheno-teratozoospermia, suggesting that Cnot7, a CCR4-associated transcriptional cofactor, is essential for spermatogenesis. Maturation of spermatids is unsynchronized and impaired in seminiferous tubules of Cnot7(-/-) mice. Transplantation of spermatogonial stem cells from male Cnot7(-/-) mice to seminiferous tubules of Kit mutant mice (Kit(W/W-v)) restores spermatogenesis, suggesting that the function of testicular somatic cells is damaged in the Cnot7(-/-) condition. The testicular phenotypes of Cnot7(-/-) mice are similar to those of mice deficient in retinoid X receptor beta (Rxrb). We further show that Cnot7 binds the AF-1 domain of Rxrb and that Rxrb malfunctions in the absence of Cnot7. Therefore, Cnot7 seems to function as a coregulator of Rxrb in testicular somatic cells and is thus involved in spermatogenesis.

Animals↗

PubMed2004

Purification, crystallization and preliminary X-ray diffraction analysis of human oncoprotein SET/TAF-1beta.

The human oncoprotein SET/TAF-1beta has been crystallized by the sitting-drop vapour-diffusion method using ammonium sulfate as a precipitant. The crystal belongs to space group C2, with unit-cell parameters a = 119.6, b = 62.8, c = 61.0 A, beta = 89.7 degrees, and contains two molecules in the asymmetric unit. A complete data set was collected to 2.8 A resolution using synchrotron radiation.

Chromosomal Proteins, Non-Histone↗

PubMed2004

Maillard reaction rate in various glassy matrices.

The Maillard Reaction (MR) rate below the glass transition temperature (T(g)) for various model glassy food systems was studied at temperatures between 40 degrees C and 70 degrees C. As a sample, freeze-dried glucose and lysine systems embedded in various glassy matrices (e.g., polyvinylpyrrolodone and trehalose) were used, and the MR rate below the T(g) was compared among the various glassy matrices. The extent of MR was estimated spectrophotometrically from the optical density at 280 nm (OD(280)), and the MR rate (k(280)) was determined as a pseudo zero order reaction rate from the time course of OD(280). Although k(280) was described by the Arrhenius plot, the temperature dependence of k(280) was almost the same and the intercept was different among the matrices. From the comparison of k(280), it was suggested that the MR rate in glassy matrix was affected not only by the T(g), but also by the hydrogen bonding between MR reactants and glassy matrix.

Calorimetry, Differential Scanning↗

PubMed2004

Association of painless acute aortic dissection with increased mortality.

OBJECTIVE: To evaluate the clinical characteristics and outcomes of patients with painless acute aortic dissection (AAD). PATIENTS AND METHODS: For this study conducted from 1997 to 2001, we searched the International Registry of Acute Aortic Dissection to identify patients with painless AAD (group 1). Their clinical features and in-hospital events were compared with patients who had painful AAD (group 2). RESULTS: Of the 977 patients in the database, 63 (6.4%) had painless AAD, and 914 (93.6%) had painful AAD. Patients in group 1 were older than those in group 2 (mean +/- SD age, 66.6 +/- 13.3 vs 61.9 +/- 14.1 years; P = .01). Type A dissection (involving the ascendIng aorta or the arch) was more frequent in group 1 (74.6% vs 60.9%; P = .03). Syncope (33.9% vs 11.7%; P < .001), congestive heart failure (19.7% vs 3.9%; P < .001), and stroke (11.3% vs 4.7%; P = .03) were more frequent presenting signs in group 1. Diabetes (10.2% vs 4.0%; P = .04), aortic aneurysm (29.5% vs 13.1%; P < .001), and prior cardiovascular surgery (48.1% vs 19.7%; P < .001) were also more common in group 1. In-hospital mortality was higher in group 1 (33.3% vs 23.2%; P = .05), especially due to type B dissection (limited to the descending aorta) (43.8% vs 10.4%; P < .001), and the prevalence of aortic rupture was higher among patients with type B dissection in group 1 (18.8% vs 5.9%; P = .04). CONCLUSION: Patients with painless AAD had syncope, congestive heart failure, or stroke. Compared with patients who have painful AAD, patients who have painless AAD have higher mortality, especially when AAD is type B.

Acute Disease↗

PubMed2003

Alteration of expression or phosphorylation status of tob, a novel tumor suppressor gene product, is an early event in lung cancer.

Tob is a member of the Tob/BTG family, a novel class of anti-proliferative proteins. To investigate the involvement of tob as a tumor suppressor gene in human lung cancer, we analyzed the expression of tob mRNA and protein in lung cancer tissue and adjacent normal lung tissue. Immunohistochemical analysis using anti-Tob antibody showed decreased expression of Tob in 72% (31/43) of lung cancer tissues. Furthermore, 95% (19/20) of squamous cell carcinoma patients showed an apparent decrease in Tob in cancer tissues, associated with smoking status. The phosphorylated form of Tob, an inactive form of Tob, was detected in 76% (16/21) of cancer tissues of adenocarcinoma patients, but not in normal alveolar epithelial cells. Either a decrease in Tob expression or an accumulation of phosphorylated Tob was observed from early clinical stages, even in bronchial dysplasia, a premalignant lesion of squamous cell carcinoma. The above findings suggest that the disruption of anti-proliferative Tob plays a distinct part in the early stage of lung carcinogenesis.

Adenocarcinoma↗

PubMed2003

Regulation of platelet-derived growth factor-A chain by Krüppel-like factor 5: new pathway of cooperative activation with nuclear factor-kappaB.

The transcription factor Krüppel-like factor 5 (KLF5) and its genetically downstream target gene platelet-derived growth factor-A (PDGF-A) chain are key factors in regulation of cardiovascular remodeling in response to stress. We show that KLF5 mediates a novel distinct delayed persistent induction of PDGF-A chain in response to the model agonist, phorbol ester, through a cis-element previously shown to mediate phorbol ester induction on to PDGF-A chain through the early growth response factor (Egr-1). Interestingly, the nuclear factor-kappaB (NF-kappaB) p50 subunit further cooperatively activates PDGF-A chain through protein-protein interaction with KLF5 but not Egr-1. RNA interference analysis confirmed that KLF5 and p50 are important for induction of PDGF-A chain. Collectively, we identify a novel regulatory pathway in which PDGF-A chain gene expression, under the control of KLF5, is cooperatively activated by the NF-kappaB p50 subunit and a pathophysiological stimulus.

Base Sequence↗

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↗

PubMed2003

KLF5/BTEB2, a Krüppel-like zinc-finger type transcription factor, mediates both smooth muscle cell activation and cardiac hypertrophy.

Cardiac and vascular biology need to be approached interactively because they share many common biological features as seen in activation of the local renin-angiotensin system, angiogenesis, and extracellular matrix production. We previously reported KLF5/BTEB2, a Krüppel-like zinc-finger type transcription factor, to activate various gene promoters that are activated in phenotypically modulated smooth muscle cells, such as a nonmuscle type myosin heavy chain gene SMemb, plasminogen activator inhibitor-1 (PAI-1), iNOS, PDGF-A, Egr-1 and VEGF receptors at least in vitro. KLF5/BTEB2 mRNA levels are downregulated with vascular development but upregulated in neointima that is produced in response to vascular injury. Mitogenic stimulation activates KLF5/BTEB2 gene expression through MEK1 and Egr-1. Chromatin immunoprecipitation assay showed KLF5/BTEB2 to be induced and to bind the promoter of the PDGF-A gene in response to angiotensin II stimulation. In order to define the role of KLF5/BTEB2 in cardiovascular remodeling, we targeted the KLF5/BTEB2 gene in mice. Homozygous mice resulted in early embryonic lethality whereas heterozygous mice were apparently normal. However, in response to external stress, arteries of heterozygotes exhibited diminished levels of smooth muscle and adventitial cell activation. Furthermore, cardiac fibrosis and hypertrophy induced by continuous angiotensin II infusion. We also found that RARa binds KLF5/BTEB2, and that Am80, a potent synthetic RAR agonist, inhibits angiotensin II-induced cardiac hypertrophy. These results indicate that KLF5/BTEB2 is an essential transcription factor that causes not only smooth muscle phenotypic modulation but also cardiac hypertrophy and fibrosis.

Angiotensin II↗