Biomedical subjects

M Suzuki

Publications and source records attributed to M Suzuki.

At least 55 records · Page 3Linked to original sources

PubMed2006

Predictors of long-term survival with pulmonary metastasectomy for osteosarcomas and soft tissue sarcomas.

AIM: The control of pulmonary metastases is important for long-term survival of the patients with osteosarcomas and soft tissue sarcomas. METHODS: To evaluate the efficacy of aggressive pulmonary metastasectomy for those patients, we reviewed 105 cases (44 osteosarcomas, and 61 soft tissue sarcomas) treated in our hospital. RESULTS: The number of metastases was only the significant risk factor for the curability of the metastasectomy (logistic regression analysis, P=0.0274). The 5-year and 10-year survival rate were 43.6% and 32%. The curability was only independent prognostic factor on multivariate analysis (P=0.0008). CONCLUSIONS: Early detection of pulmonary metastasis, multimodal perioperative treatment, and design for minimizing the volume of resected lung tissues will enable complete and repeat resections for the achievement of long-term survival.

Adolescent↗

PubMed2005

Intraoperative monitoring of penile and buttock blood flow during endovascular abdominal aortic aneurysm repair.

OBJECTIVE: The purpose of this study was to assess the pelvic circulation during endovascular abdominal aortic aneurysm repair (EVAR) with a new monitoring system measuring penile and buttock blood flow. METHODS: We measured penile brachial pressure index (PBI) during EVAR by pulse-volume-plethysmography (form PWV/ABItrade mark). We also measured bilateral gluteal tissue oxygen metabolism with near-infrared spectroscopy to provide a gluteal tissue oxygenation index (TOI). Twenty-two men who underwent aortouni-iliac stentgraft with crossover bypass for exclusion of abdominal aortic aneurysm were studied. Twelve patients underwent aorto-uni-common iliac artery stentgraft (CIA) and ten underwent aorto-uni-external iliac artery stentgraft (EIA). RESULTS: In all patients, there was an immediate reduction in PBI during the EVAR procedure. After revascularization of the ipsilateral limb of the stent graft, the recovery of PBI was significantly less in EIA group. After the completion of crossover bypass, PBI in both groups recovered to the baseline values. In both groups there was a bilateral reduction in gluteal TOI during malperfusion of the internal iliac artery. After revascularization of ipsilateral limb of the stent graft, the ipsilateral TOI recovered to the baseline level in CIA patients, but recovery was incomplete in EIA patients. In contrast, contra-lateral TOI remained low in both groups after revascularization of ipsilateral limb of the stent graft. Only after completion of crossover bypass did the contra-lateral TOI recover to baseline level in both groups. CONCLUSIONS: Both TOI at the buttocks and PBI are a sensitive reflection of pelvic haemodynamics. Penile blood flow and bilateral gluteal blood flow are supplied via different circulations and both should be monitored for full assessment of the pelvic circulation.

Aged↗

PubMed2005

DNA methylation-associated inactivation of TGFbeta-related genes DRM/Gremlin, RUNX3, and HPP1 in human cancers.

The transforming growth factor beta (TGFbeta)-signalling pathway is deregulated in many cancers. We examined the role of gene silencing via aberrant methylation of DRM/Gremlin and HPP1, which inhibit TGFbeta signalling, and RUNX3, which facilitates TGFbeta-signalling, of all genes that are thought to be tumour suppressors, are aberrantly expressed, and are thus thought to have important role in human cancers. We examined DRM/Gremlin mRNA expression in 44 cell lines and the promoter methylation status of DRM/Gremlin, HPP1, and RUNX3 in 44 cell lines and 511 primary tumours. The loss of DRM/Gremlin mRNA expression in human cancer cell lines is associated with DNA methylation, and treatment with the methylation inhibitor-reactivated mRNA expression (n=13). Methylation percentages of the three genes ranged from 0-83% in adult tumours and 0-50% in paediatric tumours. Methylation of DRM/Gremlin was more frequent in lung tumours in smokers, and methylation of all three genes was inversely correlated with prognosis in patients with bladder or prostate cancer. Our results provide strong evidence that these TGFbeta-related genes are frequently deregulated through aberrant methylation in many human malignancies.

Aged↗

PubMed2005

A short gamma-ray burst apparently associated with an elliptical galaxy at redshift z = 0.225.

Gamma-ray bursts (GRBs) come in two classes: long (> 2 s), soft-spectrum bursts and short, hard events. Most progress has been made on understanding the long GRBs, which are typically observed at high redshift (z approximately 1) and found in subluminous star-forming host galaxies. They are likely to be produced in core-collapse explosions of massive stars. In contrast, no short GRB had been accurately (< 10'') and rapidly (minutes) located. Here we report the detection of the X-ray afterglow from--and the localization of--the short burst GRB 050509B. Its position on the sky is near a luminous, non-star-forming elliptical galaxy at a redshift of 0.225, which is the location one would expect if the origin of this GRB is through the merger of neutron-star or black-hole binaries. The X-ray afterglow was weak and faded below the detection limit within a few hours; no optical afterglow was detected to stringent limits, explaining the past difficulty in localizing short GRBs.

Journal Article↗

PubMed2005

Discovery of the short gamma-ray burst GRB 050709.

Gamma-ray bursts (GRBs) fall into two classes: short-hard and long-soft bursts. The latter are now known to have X-ray and optical afterglows, to occur at cosmological distances in star-forming galaxies, and to be associated with the explosion of massive stars. In contrast, the distance scale, the energy scale and the progenitors of the short bursts have remained a mystery. Here we report the discovery of a short-hard burst whose accurate localization has led to follow-up observations that have identified the X-ray afterglow and (for the first time) the optical afterglow of a short-hard burst; this in turn led to the identification of the host galaxy of the burst as a late-type galaxy at z = 0.16 (ref. 10). These results show that at least some short-hard bursts occur at cosmological distances in the outskirts of galaxies, and are likely to be caused by the merging of compact binaries.

Journal Article↗

PubMed2005

Modulation of the Ca2 permeable cation channel TRPV4 by cytochrome P450 epoxygenases in vascular endothelium.

TRPV4 is a broadly expressed Ca2+-permeable cation channel in the vanilloid subfamily of transient receptor potential channels. TRPV4 gates in response to a large variety of stimuli, including cell swelling, warm temperatures, the synthetic phorbol ester 4alpha-phorbol 12,13-didecanoate (4alpha-PDD), and the endogenous lipid arachidonic acid (AA). Activation by cell swelling and AA requires cytochrome P450 (CYP) epoxygenase activity to convert AA to epoxyeicosatrienoic acids (EETs) such as 5,6-EET, 8,9-EET, which both act as direct TRPV4 agonists. To evaluate the role of TRPV4 and its modulation by the CYP pathway in vascular endothelial cells, we performed Ca2+ imaging and patch-clamp measurements on mouse aortic endothelial cells (MAECs) isolated from wild-type and TRPV4(-/-) mice. All TRPV4-activating stimuli induced robust Ca2+ responses in wild-type MAECs but not in MAECs isolated from TRPV4(-/-) mice. Upregulation of CYP2C expression by preincubation with nifedipine enhanced the responses to AA and cell swelling in wild-type MAECs, whereas responses to other stimuli remained unaffected. Conversely, inhibition of CYP2C9 activity with sulfaphenazole abolished the responses to AA and hypotonic solution (HTS). Moreover, suppression of EET hydrolysis using 1-adamantyl-3-cyclo-hexylurea or indomethacin, inhibitors of soluble epoxide hydrolases (sEHs), and cyclooxygenases, respectively, enhanced the TRPV4-dependent responses to AA, HTS, and EETs but not those to 4alpha-PDD or heat. Together, our data establish that CYP-derived EETs modulate the activity of TRPV4 channels in endothelial cells and shows the unraveling of novel modulatory pathways via CYP2C modulation and sEH inhibition.

8,11,14-Eicosatrienoic Acid↗

PubMed2005

Antisense transcription in the mammalian transcriptome.

Antisense transcription (transcription from the opposite strand to a protein-coding or sense strand) has been ascribed roles in gene regulation involving degradation of the corresponding sense transcripts (RNA interference), as well as gene silencing at the chromatin level. Global transcriptome analysis provides evidence that a large proportion of the genome can produce transcripts from both strands, and that antisense transcripts commonly link neighboring "genes" in complex loci into chains of linked transcriptional units. Expression profiling reveals frequent concordant regulation of sense/antisense pairs. We present experimental evidence that perturbation of an antisense RNA can alter the expression of sense messenger RNAs, suggesting that antisense transcription contributes to control of transcriptional outputs in mammals.

Animals↗

PubMed2005

Transcription factor specificity protein 1 (Sp1) is the main regulator of nerve growth factor-induced sphingosine kinase 1 gene expression of the rat pheochromocytoma cell line, PC12.

Sphingosine kinase (SPHK) is known to exert an anti-apoptic role in various cells and cell lines. We previously reported that human brain is rich in SPHK1 (Murate et al. 2001). After showing a high expression of SPHK1 in rat brain, we examined the gene expression mechanism using nerve growth factor (NGF)-stimulated rat PC12 cells. With RT-PCR, we found that both rat brain and PC12 utilized exon 1d mostly out of eight untranslated first exons. NGF induced an increase in SPHK enzyme activity and protein about double those in PC12 cells, and NGF-induced SPHK1 mRNA was three times higher than in the control. The minimal 5' promoter was determined, and TrkA specific inhibitor K252a inhibited the NGF-induced promoter activity of SPHK1. The truncation or mutation of putative transcription factor-binding motifs revealed that one specificity protein 1 (Sp1) binding motif of the 5' region of exon 1d is prerequisite. Electrophoresis mobility shift assay confirmed the promoter analysis, indicating increased Sp1 protein binding to this motif after NGF treatment. Chromatin immunoprecipitation assay also showed the binding of Sp1 and the promoter region in vivo. These results suggest the signal transduction pathway from NGF receptor TrkA to transcription factor Sp1 protein binding to the promoter Sp1-like motif in NGF-induced rat SPHK1 gene expression.

Animals↗

PubMed2005

Four-electron shell structures and an interacting two-electron system in carbon-nanotube quantum dots.

Low-temperature transport measurements have been carried out on single-wall carbon-nanotube quantum dots in a weakly coupled regime in magnetic fields. Four-electron shell filling was observed, and the magnetic field evolution of each Coulomb peak was investigated. Excitation spectroscopy measurements have revealed Zeeman splitting of single particle states for one electron in the shell, and demonstrated singlet and triplet states with direct observation of the exchange splitting at zero-magnetic field for two electrons in the shell, the simplest example of Hund's rule.

Journal Article↗

PubMed2005

A giant gamma-ray flare from the magnetar SGR 1806-20.

Two classes of rotating neutron stars-soft gamma-ray repeaters (SGRs) and anomalous X-ray pulsars-are magnetars, whose X-ray emission is powered by a very strong magnetic field (B approximately 10(15) G). SGRs occasionally become 'active', producing many short X-ray bursts. Extremely rarely, an SGR emits a giant flare with a total energy about a thousand times higher than in a typical burst. Here we report that SGR 1806-20 emitted a giant flare on 27 December 2004. The total (isotropic) flare energy is 2 x 10(46) erg, which is about a hundred times higher than the other two previously observed giant flares. The energy release probably occurred during a catastrophic reconfiguration of the neutron star's magnetic field. If the event had occurred at a larger distance, but within 40 megaparsecs, it would have resembled a short, hard gamma-ray burst, suggesting that flares from extragalactic SGRs may form a subclass of such bursts.

Journal Article↗

PubMed2005

NK105, a paclitaxel-incorporating micellar nanoparticle formulation, can extend in vivo antitumour activity and reduce the neurotoxicity of paclitaxel.

Paclitaxel (PTX) is one of the most effective anticancer agents. In clinical practice, however, high incidences of adverse reactions of the drug, for example, neurotoxicity, myelosuppression, and allergic reactions, have been reported. NK105, a micellar nanoparticle formulation, was developed to overcome these problems and to enhance the antitumour activity of PTX. Via the self-association process, PTX was incorporated into the inner core of the micelle system by physical entrapment through hydrophobic interactions between the drug and the well-designed block copolymers for PTX. NK105 was compared with free PTX with respect to their in vitro cytotoxicity, in vivo antitumour activity, pharmacokinetics, pharmacodynamics, and neurotoxicity. Consequently, the plasma area under the curve (AUC) values were approximately 90-fold higher for NK105 than for free PTX because the leakage of PTX from normal blood vessels was minimal and its capture by the reticuloendothelial system minimised. Thus, the tumour AUC value was 25-fold higher for NK105 than for free PTX. NK105 showed significantly potent antitumour activity on a human colorectal cancer cell line HT-29 xenograft as compared with PTX (P<0.001) because the enhanced accumulation of the drug in the tumour has occurred, probably followed by its effective and sustained release from micellar nanoparticles. Neurotoxicity was significantly weaker with NK105 than with free PTX. The neurotoxicity of PTX was attenuated by NK105, which was demonstrated by both histopathological (P<0.001) and physiological (P<0.05) methods for the first time. The present study suggests that NK105 warrants a clinical trial for patients with metastatic solid tumours.

Animals↗

PubMed2005

Aberrant methylation of SPARC in human lung cancers.

SPARC (secreted protein acidic and rich in cysteine) is an extracellular Ca2+-binding matricellular glycoprotein associated with the regulation of cell adhesion and growth. We investigated loss of expression of SPARC gene and promoter methylation in lung cancers and correlated the data with clinicopathological features. We observed loss of SPARC expression in 12 of 20 (60%) lung cancer cell lines. Treatment of expression-negative cell lines with a demethylating agent restored expression in all cases. Methylation frequencies of SPARC gene were 55% in 20 lung cancer cell lines. Primary tumours had methylation at a rate of 69% (119 of 173), while nonmalignant lung tissues (n=60) had very low rates (3%). In lung adenocarcinomas, SPARC methylation correlated with a negative prognosis (P=0.0021; relative risk 4.65, 95% confidence interval 1.75-12.35, multivariate Cox's proportional-hazard model). Immunostaining revealed protein expression in bronchial epithelium (weak intensity) and in juxtatumoral stromal tissues (strong intensity) accompanied by frequent loss in cancer cells that correlated with the presence of methylation (P<0.001). Our findings are of biological interest and potentially of clinical importance in human lung cancers.

Adenocarcinoma↗

PubMed2005

A new three-dimensional automatic bodymarker system for transvaginal ultrasonography.

OBJECTIVE: To evaluate the accuracy and usefulness of a newly developed three-dimensional automatic bodymarker system for transvaginal ultrasonography. METHODS: A bodymarker system which utilizes an electromagnetic field to specify the probe position was developed. Software was written which enabled the positional information of the probe and the ultrasound image to be simultaneously displayed on a personal computer. The bodymarker was displayed as a three-dimensional graphic model. The differences between the estimated and the actual position--i.e. the error--for both position (x, y and z) and angles (azimuth, elevation and roll) of the probe were measured. The movement of the probe was then evaluated in healthy female volunteers and the comparative time required for ultrasound examination was determined. RESULTS: Both the position and the angles of the probe were accurately shown in the computer display. The errors were 1.0 mm and 0.7 degrees (median) for position and angle, respectively. The system was also shown to work well in healthy female volunteers. Calibration of the new system required only 5.0 seconds, compared with an average of 7.6 seconds for the conventional bodymarker. CONCLUSION: The newly developed three-dimensional automatic transvaginal bodymarker system provides an accurate indication of probe position and its tilting angle. It works well in healthy female volunteers and speeds up the examination time. It may be clinically useful for transvaginal ultrasound examination.

Calibration↗

PubMed2005

Extensor mechanism laxity at the metacarpophalangeal joint as identified by a new provocative test: predisposition to dislocation.

A tendon subluxation test was performed on the unaffected side in 13 patients with traumatic extensor tendon dislocation of the middle finger and on both middle fingers in 800 healthy controls to identify extensor mechanism laxity at the metacarpophalangeal joint. Ten of the 13 patients with dislocation had laxity of middle finger extensor tendon, compared with 174 of the 800 (22%) controls. The difference in these rates of extensor tendon laxity is significant (P<0.0001), and suggests that extensor mechanism laxity at the metacarpophalangeal joint may predispose to traumatic extensor tendon dislocation.

Adult↗

PubMed2005

Autoantibodies against the amino terminal of alpha-enolase are a useful diagnostic marker of Hashimoto's encephalopathy.

We investigated autoantibodies and their epitope(s) in Hashimoto's encephalopathy associated with Hashimoto's thyroiditis. In a proteomic analysis, they proved to recognize alpha-enolase. We further searched the epitope region in alpha-enolase using different regions of recombinant proteins expressed in cultured human cells. The amino terminal region was recognized by autobodies from a much higher proportion of patients with Hashimoto's encephalopathy (83.3%; 5/6) than from patients with Hashimoto's thyroiditis (11.8%; 2/17), and not at all by sera from controls (25 healthy individuals and 25 controls with other neurological disorders) (0%; 0/50). Neither the carboxyl terminal nor the mid-region of alpha-enolase showed specificity for Hashimoto's encephalopathy. Autoantibodies against the amino terminal of alpha-enolase are a useful diagnostic marker for Hashimoto's encephalopathy.

Adult↗

PubMed2005

Involvement of Rho-kinase in inflammatory and neuropathic pain through phosphorylation of myristoylated alanine-rich C-kinase substrate (MARCKS).

Myristoylated alanine-rich C-kinase substrate (MARCKS) is a major in vivo substrate for protein kinase C in the brain and has been implicated in cellular processes associated with cytoskeletal restructuring such as synaptic trafficking and neurotransmitter release. A phosphorylation-site specific antibody against Ser159-phospho-MARCKS (pS159-Mar-Ab) revealed that MARCKS is phosphorylated at Ser159 by Rho-kinase and that its phosphorylation is inhibited by the Rho-kinase specific inhibitor H-1152. Since the function of MARCKS is regulated by phosphorylation at multiple sites, here we examined the involvement of Rho-kinase in relation to phosphorylation of MARCKS at Ser159 in inflammatory and neuropathic pain by H-1152. When intrathecally administered 10 min before s.c. injection of formalin, H-1152 at 10 and 100 ng attenuated the second-phase, but not the first-phase, pain-like behaviors in the formalin test. Neuropathic pain induced by selective L5 spinal nerve transection was also relieved by intrathecal injection of H-1152. Nitric oxide synthase activity visualized by NADPH diaphorase histochemistry increased in the superficial layer of the spinal cord 30 min after formalin injection and 7 days after nerve transection, which were blocked by H-1152. Phosphorylation of MARCKS at Ser159 was detected in the spinal cord by pS159-Mar-Ab and the level of phosphorylation increased in the superficial layer after nerve transection. In contrast, immunoreactivities of neuronal nitric oxide synthase and MARCKS did not change significantly in the spinal cord before and after nerve transection. Taken together, the present study demonstrates that Rho-kinase is involved in inflammatory pain and the maintenance of neuropathic pain through phosphorylation of MARCKS at Ser159.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2005

Morphological brain changes associated with Schneider's first-rank symptoms in schizophrenia: a MRI study.

BACKGROUND: Schneider's first-rank symptoms involve an alienated feature of the sense of one's own mental or physical activity. To clarify the brain morphological basis for the production of these symptoms, volumes of the frontal and medial temporal regions and their clinical correlates were examined in patients with schizophrenia. METHOD: Twenty-two patients with schizophrenia and 44 age- and gender-matched healthy control subjects were included. All patients were in their psychotic episodes with definite Schneiderian symptoms, rated by using the Scale for Assessment of Positive Symptoms. Volumetric measurements of high-resolution magnetic resonance imaging were performed in the prefrontal area, cingulate gyrus, and precentral gyrus, and the medial temporal structures such as the amygdala, hippocampus, and parahippocampal gyrus. RESULTS: Patients had significantly decreased volumes in the cingulate gray matter and the amygdala compared to controls. In the patient group, Schneiderian symptom severity showed significant inverse correlations with volumes of the right posterior cingulate gray matter and of the left anterior parahippocampal gyrus. CONCLUSIONS: Schneiderian symptoms may be associated with morphological abnormalities in the limbic-paralimbic regions such as the cingulate gyrus and parahippocampal gyrus, which possibly serve the self-monitoring function and the coherent storage and reactivation of information.

Adult↗

PubMed2005

Image-guided stereotactic radiosurgery with the CyberKnife for pituitary adenomas.

This study demonstrates the clinical usefulness of image-guided fractionated stereotactic radiosurgery with the CyberKnife system. Twenty-one patients with pituitary adenomas received image-guided stereotactic radiosurgery with the CyberKnife, and were followed up for more than 18 months. The patients consisted of 14 with non-functioning adenomas, 3 with prolactinomas, 2 with acromegaly, and 2 with ACTH-producing tumors. In 20 cases, fractionated radiosurgery was performed. The change in the tumor volume, visual acuity, hormonal function, and complications by this therapy were analyzed in each case. The volume of the tumors ranged from 0.2 cm (3) to 34.9 cm (3) (mean +/- SD: 11.3 +/- 9.2 cm (3)). The mean volumes of the non-functioning and functioning adenomas were 13.3 cm (3) and 7.5 cm (3), respectively. The marginal irradiation dose ranged from 6.4 Gy to 27.7 Gy (mean: non-functioning adenomas 12.6 Gy, functioning adenomas 17.5 Gy), as a dose of a single fraction. The follow-up periods ranged from 18 months to 59 months (mean +/- SD: 35.3 +/- 10.7 months). The tumor control rate was 95.2 %. In 1 case, visual acuity worsened due to cystic enlargement of the tumor. Hormonal function improved in all of the 7 functioning adenomas. The hormone level normalized in 1 prolactinoma, and decreased to less than normal in 1 ACTH-producing adenoma. In 2 cases, hypopituitarism occurred after the therapy. Image-guided stereotactic radiosurgery with the CyberKnife is effective and safe against relatively large pituitary adenomas. Careful long-term follow-up of the patients is necessary because of delayed cystic enlargement of the tumor in rare cases.

Adenoma↗