Biomedical subjects

Toru Suzuki

Publications and source records attributed to Toru Suzuki.

At least 19 recordsLinked to original sources

PubMed2006

Differential serum proteomic analysis in a model of metabolic disease.

Protein profiling would aid in better understanding the pathophysiology of metabolic disease. Here, we report on differential proteomic analysis using an animal model of diabetes mellitus and associated metabolic disorders (Otsuka Long-Evans Tokushima Fatty rat). Serum was analyzed by a new two-dimensional liquid chromatography system which separated proteins by chromatofocusing and subsequent reversed-phase chromatography. This is the first application of this approach to differential serum proteomics. Differentially expressed proteins, identified with MALDI-TOF mass spectrometry, included apolipoproteins and alpha2-HS-glycoprotein. These findings add to our understanding of the underlying pathophysiology. This new proteomic analysis is a promising tool to elucidate disease mechanisms.

Animals↗

PubMed2006

Degradation of Tob1 mediated by SCFSkp2-dependent ubiquitination.

Tob1, a member of the Tob/BTG family, is involved in the control of G(1)-S progression by suppressing cyclin D1 expression and acts as a tumor suppressor gene. Tob1 was reported to have a quick turnover through the ubiquitin-proteasome pathway, but proteins involved in this process are still unknown. We showed that Skp2, a substrate-targeting subunit of the SCF (Skp1/Cul1/F-box protein) ubiquitin ligase complex, was involved in ubiquitin-dependent degradation of Tob1. Skp2 interacted with Tob1 and facilitated ubiquitination of Tob1 in intact cells as well as in vitro. Skp2 mutants without the F-box or leucine rich repeat were not able to bind to Tob1 and did not enhance ubiquitination of Tob1. Tob1 was stabilized in both Skp2(-/-) mouse fibroblasts and Skp2 knockdown HeLa cells. Moreover, cyclin D1 expression was suppressed in Skp2 knockdown HeLa cells. These data suggest that Tob1 is a novel target for degradation by the SCF-Skp2 ubiquitin ligase.

Cell Cycle↗

PubMed2006

Role and results of surgery in acute type B aortic dissection: insights from the International Registry of Acute Aortic Dissection (IRAD).

BACKGROUND: The clinical profiles and outcomes of patients treated surgically for acute type B aortic dissection (ABAD) are often reported for those in small series or for those cared for at a single institution over a long time period, during which a continuous evolution in techniques has occurred. Accordingly, we sought to evaluate the clinical features and surgical results of patients enrolled in the International Registry of Acute Aortic Dissection by identifying primary factors that influenced surgical outcome and estimating average surgical mortality for ABAD in the current era. METHODS AND RESULTS: A comprehensive analysis of 290 clinical variables and their relation to surgical outcomes for 82 patients who required surgery for ABAD (from a population of 1256 patients; mean+/-SD age, 60.6+/-15.0 years; 82.9% male) and who were enrolled in the International Registry of Acute Aortic Dissection was performed. The overall in-hospital mortality was 29.3%. Factors associated with increased surgical mortality based on univariate analysis were preoperative coma or altered consciousness, partial thrombosis of the false lumen, evidence of periaortic hematoma on diagnostic imaging, descending aortic diameter >6 cm, right ventricle dysfunction at surgery, and shorter time from the onset of symptoms to surgery. Factors associated with favorable outcomes included radiating pain, normotension at surgery (systolic blood pressure 100 to 149 mm Hg), and reduced hypothermic circulatory arrest time. The 2 independent predictors of surgical mortality were age >70 years (odds ratio, 4.32; 95% confidence interval, 1.30 to 14.34) and preoperative shock/hypotension (odds ratio, 6.05; 95% confidence interval, 1.12 to 32.49). CONCLUSIONS: The present study provides insights into current-day clinical profiles and surgical outcomes of ABAD. Knowledge about different preoperative clinical conditions may help surgeons in making treatment decisions among these high-risk patients.

Acute Disease↗

PubMed2006

Glass transition and enthalpy relaxation of amorphous lactose glass.

The glass transition temperature, T(g), and enthalpy relaxation of amorphous lactose glass were investigated by differential scanning calorimetry (DSC) for isothermal aging periods at various temperatures (25, 60, 75, and 90 degrees C) below T(g). Both T(g) and enthalpy relaxation were found to increase with increasing aging time and temperature. The enthalpy relaxation increased approximately exponentially with aging time at a temperature (90 degrees C) close to T(g) (102 degrees C). There was no significant change observed in the enthalpy relaxation around room temperature (25 degrees C) over an aging period of 1month. The Kohlrausch-Williams-Watts (KWW) model was able to fit the experimental enthalpy relaxation data well. The relaxation distribution parameter (beta) was determined to be in the range 0.81-0.89. The enthalpy relaxation time constant (tau) increased with decreasing aging temperature. The observed enthalpy relaxation data showed that molecular mobility in amorphous lactose glass was higher at temperatures closer to T(g). Lactose glass was stable for a long time at 25 degrees C. These findings should be helpful for improving the processing and storage stability of amorphous lactose and lactose containing food and pharmaceutical products.

Calorimetry, Differential Scanning↗

PubMed2006

Low-temperature glass transitions of quenched and annealed bovine serum albumin aqueous solutions.

To investigate the glass transition behaviors of a 20% (w/w) aqueous solution of bovine serum albumin, heat capacities and enthalpy relaxation rates were measured by adiabatic calorimetry at temperatures ranging from 80 to 300 K. One series of measurements was carried out after quenching from 300 down to 80 K and another after annealing in 200-240 K. The quenched sample showed a heat capacity jump indicating a glass transition temperature T(g) = 170 K, and the annealed sample showed a smaller jump with the T(g) shifted toward the higher temperature side. The temperature dependence of the enthalpy relaxation rates for the quenched sample indicated the presence of two enthalpy relaxation effects: one at around 110 K and the other over a wide temperature range (120-190 K). The annealed sample showed three separate relaxation effects giving 1) T(g) = 110 K, 2) 135 K, and 3) temperature higher than 180 K, whereas nothing around 170 K. These effects were thought to originate, respectively, from the rearrangement motions of 1) primary hydrate water forming a direct hydrogen bond with the protein, 2) part of the internal water localized in the opening of a protein structure, and 3) the disordered region in the protein.

Phase Transition↗

PubMed2006

Enthalpy relaxation of freeze concentrated sucrose-water glass.

The enthalpy relaxation of freeze concentrated sucrose-water glass was investigated using 40% sucrose, differential scanning calorimetry (DSC) with isothermal ageing for 1-6 days at various temperatures (-70, -65, -60, and -55 degrees C). The enthalpy relaxation was observed as an endothermic peak superimposed on the endothermic step-wise change due to the glass transition around -47 degrees C. The enthalpy relaxation was found to increase with ageing time and temperature. An 80% sucrose glass was also investigated at ageing temperatures of -60 and -65 degrees C, and this material exhibited a similar glass transition and enthalpy relaxation to that observed with the frozen 40% sucrose solution. The calculated activation energy of the enthalpy relaxation of the sucrose-water glass was smaller than that reported for pure sucrose. These results suggest that the freeze concentrated sucrose-water glass could have a higher molecular mobility and less stability than pure sucrose glass.

Calorimetry, Differential Scanning↗

PubMed2006

Zygotically activated genes are suppressed in mouse nuclear transferred embryos.

Mammalian oocytes have the ability to confer totipotency to terminally differentiated somatic cell nuclei. Viable cloned animals have been produced by somatic cell nuclear transfer (NT) into oocytes in many mammalian species including mouse. However, the success rates of the production were quite low in all species. Many studies have measured differences in gene expression between NT and fertilized embryos in relatively advanced stages of development such as pre- and post-natal stages or the blastocyst stage. In the present study, we compared gene expression patterns using differential display RT-PCR (DDRT-PCR) between the NT and IVF embryos at the 2-cell stage to detect some abnormalities affecting later development of NT embryos. Aberrant gene expression was detected in NT embryos compared with IVF embryos, and MuERV-L and Dnaja2 genes were down-regulated and Inpp5b and Chst12 genes were up-regulated in the NT embryos. Further analysis showed that the expression of zygotically activated genes such as Interferon-gamma, Dub-1, Spz1, DD2106 (unknown gene), and DD2111 (unknown gene) were suppressed in NT embryos, suggesting that the cellular process involved in the nuclear reprogramming of somatic nucleus is not appropriately regulated.

Animals↗

PubMed2006

Plasma levels of metalloproteinases-9 and -2 in the acute and subacute phases of type A and type B aortic dissection.

OBJECTIVES: Aortic dissection is characterized by an acute phase of medial dissection and a subacute-chronic phase of vessel wall repair. Matrix metalloproteinases (MMPs), through degradation of extracellular matrix, may play an important role in these processes. Elevation of MMPs might represent an opportunity to diagnostically characterize acute or chronic aortic processes. We examined the potential diagnostic role of MMP-9 and MMP-2 in different phases of aortic dissection. METHODS: Plasma levels of MMPs were evaluated by enzyme-linked immunosorbent assay technique in 13 patients affected by acute aortic dissection (nine type A, four type B). Ten healthy subjects were used as controls. In patients with type B aortic dissection treated medically, plasma curves (1, 3, 6, 12, 24, 48 and 96 h; 1 and 2 weeks; and 2 months from symptom onset) were also assessed. Aortic tissue samples obtained during surgery were evaluated by immunohistochemistry and western blot for MM-9 and tissue inhibitor of metalloproteinase-1 expression. RESULTS: MMP-9 plasma levels were increased in patients affected by type A and type B aortic dissection presenting within 1 h from onset of symptoms compared to controls (29.3 +/- 16.1 and 16.7 +/- 2.1 ng/ml versus 7.74 +/- 1.6 ng/ml, P < 0.03, respectively). No differences were detected in MMP-2 plasma levels compared to controls (4.84 +/- 1.2 ng/ml for type A and 6.16 +/- 0.6 ng/ml versus 3.17 +/- 1.0 ng/ml for controls, P = NS, respectively). In type B aortic dissection, mean MMP-9 plasma levels increased significantly from hospital admission to 2-month follow-up (16.7 +/- 2.1 ng/ml versus 58.0 +/- 8.2 ng/ml, P < 0.0001). Conversely, no difference in MMP-2 plasma levels was evident during follow-up (6.16 +/- 0.6 ng/ml versus 4.28 +/- 0.4 ng/ml, P = NS, respectively). Low-moderate (+/++) expression of MMP-9 was evident at immunohistochemistry in the acute phase whereas a marked expression (++++) was detected in the subacute phase. CONCLUSIONS: This pilot study suggests that the acute and subacute phase of both type A and type B aortic dissection is characterized by an increase of MMP-9 plasma levels. A marked increase is also evident in the subacute phase of medically treated type B aortic dissection as an expression of aortic wall remodelling. An increase of proteolytic activity could accompany attempts of the dissected aorta to heal itself but such a phenomena might further weaken the aortic wall, predisposing it to dilation and/or rupture.

Acute Disease↗

PubMed2006

Hydrostatic pressure modulates mRNA expressions for matrix proteins in human meniscal cells.

There have been few reports describing the effects of mechanical loading on the metabolism of meniscal cells. The aim of this study was to investigate the effects of hydrostatic pressure on meniscal cell metabolism. Human meniscal cells were cultured in alginate beads for 3 days. They were then subjected to 4 MPa hydrostatic pressure for 4 hours in either a static or cyclic (1 Hz) mode using a specially designed and constructed system. Immediately after the pressure application, the messenger RNA levels for aggrecan, type I collagen, matrix metalloproteinases (MMP) -1, -3, -9, -13 and tissue inhibitors of metalloproteinases (TIMP) -1 and -2 were measured. It was found that the application of static hydrostatic pressure caused a significant decrease in mRNA expression for MMP-1 and -13 (p<0.05). In contrast, the application of cyclic hydrostatic pressure was associated with a significant increase in type I collagen (p<0.01), TIMP-1 and -2 mRNA expression (p<0.01). These results would suggest that hydrostatic pressure in isolation can modulate mRNA expressions for matrix proteins in meniscal cells.

Adolescent↗

PubMed2006

[Prostatic duct adenocarcinoma with pagetoid spread on the glans penis: a case report].

A 75-year-old male visited our division with asymptomatic erythema on the glans penis which he first noticed six months earlier. The patient underwent total cystoprostatectomy under the diagnosis of urothelial carcinoma of the urinary bladder four years earlier. At the time, the prostatectomy specimen incidentally revealed a prostatic acinar adenocarcinoma at the bilateral peripheral zone. A skin biopsy of the erythema revealed intraepithelial Paget's cells, and the patient underwent total penectomy under the diagnosis of extramammary Paget's disease. Histopathological examination revealed continuous intraepithelial Paget's cells from the glans penis to the urethral navicular fossa, and a ductal carcinoma was detected beneath the urethral mucosa to the excisional margin. Because the Paget's cells expressed cytokeratin 20, the tumor was diagnosed as Pagetoid spread rather than Paget's disease. Re-examination of the previous prostatectomy specimen revealed prostatic duct adenocarcinoma with prostatic acinar adenocarcinoma. Therefore, the final diagnosis was prostatic duct adenocarcinoma with Pagetoid spread to the glans penis. Follow up at nine months revealed neither local recurrence, nor distant metastases, although no adjuvant therapy has been given.

Adenocarcinoma↗

PubMed2005

Nodal domain distribution for a nonintegrable two-dimensional anharmonic oscillator.

We investigate the transition from integrable to chaotic dynamics in the quantum mechanical wave functions from the point of view of the nodal structure by employing a two-dimensional quartic oscillator. We find that the number of nodal domains is drastically reduced as the dynamics of the system changes from integrable to nonintegrable, and then gradually increases as the system becomes chaotic. The number of nodal intersections with the classical boundary as a function of the level number shows a characteristic dependence on the dynamics of the system, too. We also calculate the area distribution of nodal domains and study the emergence of the power law behavior with the Fisher exponent in the chaotic limit.

Journal Article↗

PubMed2005

CD24 is expressed specifically in the nucleus pulposus of intervertebral discs.

Intervertebral disc (IVD) consists of a soft gelatinous material in its center, the nucleus pulposus (NP), bounded peripherally by fibrocartilage, annulus fibrosus (AF). Despite the number of patients with IVD degeneration, gene expression analysis has not been undertaken in NP and therefore little is known about the molecular markers expressed in NP. Here, we undertook a microarray screen in NP with the other nine tissues to identify the specific cell surface markers for NP. Five membrane associating molecules out of 10,490 genes were identified as highly expressing genes in NP compared with the other tissues. Among them, we identified CD24, a glycosylphosphatidylinositol (GPI) anchor protein as a cell surface marker for NP. CD24 expression was also detected in the herniated NP and chordoma, a malignant primary tumor derived from notochordal cells, while it was absent in chondrosarcoma. Therefore, CD24 is a molecular marker for NP as well as the diseases of IVD.

Animals↗

PubMed2005

Implications of periaortic hematoma in patients with acute aortic dissection (from the International Registry of Acute Aortic Dissection).

The clinical profiles, presentation, and outcomes of patients with acute aortic dissections and associated periaortic hematomas on aortic imaging have not been described in a large cohort. This study sought to assess the prognostic implications of periaortic hematomas in patients with aortic dissections and to identify factors associated with in-hospital mortality in patients with periaortic hematomas. The study population was 971 patients with acute aortic dissections enrolled in the International Registry of Acute Aortic Dissection with available imaging data on presentation with the presence or absence of periaortic hematomas. Patients with periaortic hematomas (n = 227, 23.4%) were more likely to be women, to have a history of hypertension and atherosclerosis, and to present early to the hospital. At presentation, they had greater frequencies of shock, cardiac tamponade, coma, and/or altered consciousness. Clinical outcomes were significantly worse in patients with periaortic hematomas, including significantly greater mortality (33% vs 20.3%, p <0.001). A multivariate model demonstrated periaortic hematomas to be an independent predictor of mortality in patients with aortic dissections (odds ratio 1.71, 95% confidence interval 1.15 to 2.54, p = 0.007). In conclusion, this study provides insight into the profiles, presentation, and outcomes of patients with periaortic hematomas and acute aortic dissections. The early identification and aggressive management of patients with periaortic hematomas may potentially improve clinical outcomes.

Acute Disease↗

PubMed2005

DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells.

Osteoclasts are bone-resorbing cells that play a pivotal role in bone remodeling. Osteoclasts form large multinuclear giant cells by fusion of mononuclear osteoclasts. How cell fusion is mediated, however, is unclear. We identify the dendritic cell-specific transmembrane protein (DC-STAMP), a putative seven-transmembrane protein, by a DNA subtraction screen between multinuclear osteoclasts and mononuclear macrophages. DC-STAMP is highly expressed in osteoclasts but not in macrophages. DC-STAMP-deficient mice were generated, and osteoclast cell fusion was completely abrogated in homozygotes despite normal expression of osteoclast markers and cytoskeletal structure. As osteoclast multinucleation was restored by retroviral introduction of DC-STAMP, loss of cell fusion was directly attributable to a lack of DC-STAMP. Defects in osteoclast multinucleation reduce bone-resorbing activity, leading to osteopetrosis. Similar to osteoclasts, foreign body giant cell formation by macrophage cell fusion was also completely abrogated in DC-STAMP-deficient mice. We have thus identified an essential regulator of osteoclast and macrophage cell fusion, DC-STAMP, and an essential role of osteoclast multinucleation in bone homeostasis.

Animals↗

PubMed2005

Phosphorylation and inactivation of Tob contributes to the progression of papillary carcinoma of the thyroid.

Tob, a member of the Tob/BTG family, is a novel anti-proliferative protein, but it becomes inactive when phosphorylated. In this study, we investigated whether Tob is phosphorylated and inactive in various thyroid neoplasms in order to elucidate how this event plays a role in their progression. Tob phosphorylation was only occasionally seen in normal follicular cells. A high level of Tob phosphorylation was observed in 42.1% of follicular adenoma, 14.3% of follicular carcinoma. In papillary carcinoma, the Tob phosphorylation level was elevated more frequently than that in follicular carcinoma, and 39.7% of specimens were classified in the high group. Tob phosphorylation level in papillary carcinoma was directly linked to tumor size, lymph node metastasis, extrathyroid extension and the presence of poorly differentiated lesion. In anaplastic carcinoma, surprisingly, Tob phosphorylation was not observed in any cases, but the deficiency of Tob expression was also observed in all these cases. These results suggest that (1) Tob phosphorylation contributes to the progression of papillary carcinoma especially in the later phase through cancellation of its anti-proliferative function, and (2) the deficiency of Tob expression is attributable to the lack of Tob phosphorylation in anaplastic carcinoma.

Adenoma↗

PubMed2005

Vascular implications of the Krüppel-like family of transcription factors.

The Krüppel-like factor (KLF) family is a recently highlighted group of zinc finger transcription factors given their important biological roles which include the vasculature. KLF2, KLF4, KLF5, and KLF6 are notable factors that have been implicated in developmental as well as pathological vascular processes. In this brief review, we provide an up-to-date summary of the physiological functions and cellular effects as well as transcriptional regulatory mechanisms of the vascular KLFs. Through such, we aim to provide a working view for understanding the pathological actions of KLFs in the vasculature.

Animals↗

PubMed2005

The deacetylase HDAC1 negatively regulates the cardiovascular transcription factor Krüppel-like factor 5 through direct interaction.

Transcription is regulated by a network of transcription factors and related cofactors that act in concert with the general transcription machinery. Elucidating their underlying interactions is important for understanding the mechanisms regulating transcription. Recently, we have shown that Krüppel-like factor KLF5, a member of the Sp/KLF family of zinc finger factors and a key regulator of cardiovascular remodeling, is regulated positively by the acetylase p300 and negatively by the oncogenic regulator SET through coupled interaction and regulation of acetylation. Here, we have shown that the deacetylase HDAC1 can negatively regulate KLF5 through direct interaction. KLF5 interacts with HDAC1 in the cell and in vitro. Gel shift DNA binding assay showed that their interaction inhibits the DNA binding activity of KLF5, suggesting a property of HDAC1 to directly affect the DNA binding affinity of a transcription factor. Reporter assay also revealed that HDAC1 suppresses KLF5-dependent promoter activation. Additionally, overexpression of HDAC1 suppressed KLF5-dependent activation of its endogenous downstream gene, platelet-derived growth factor-A chain gene, when activated by phorbol ester. Further, HDAC1 binds to the first zinc finger of KLF5, which is the same region where p300 interacts with KLF5 and, intriguingly, HDAC1 inhibits binding of p300 to KLF5. Direct competitive interaction between acetylase and deacetylase has been hitherto unknown. Collectively, the transcription factor KLF5 is negatively regulated by the deacetylase HDAC1 through direct effects on its activities (DNA binding activity, promoter activation) and further through inhibition of interaction with p300. These findings suggest a novel role and mechanism for regulation of transcription by deacetylase.

Acetyltransferases↗

PubMed2005

Stage-specific expression of microRNAs during Xenopus development.

MicroRNAs (miRNAs) repress target genes at the post-transcriptional level and play important roles in development and cell lineage decision. However, in vertebrates, both the targets of miRNAs and their expression profile during development are poorly understood. Here, we report the detailed expression profiles of miRNAs from oocyte stage to tadpole stage in Xenopus laevis. As development proceeds, a variety of miRNAs start to be expressed. Most miRNAs emerged at a specific stage and were continuously expressed until the tadpole stage. In addition, we identified a novel miRNA that was expressed only at specific stages of development and that is likely to have roles in midblastula transition.

Animals↗