PubMed Health⌕ Search

Biomedical subjects

Manabu Minami

Publications and source records attributed to Manabu Minami.

At least 19 recordsLinked to original sources
PubMed2006

Mulberry leaf aqueous fractions inhibit TNF-alpha-induced nuclear factor kappaB (NF-kappaB) activation and lectin-like oxidized LDL receptor-1 (LOX-1) expression in vascular endothelial cells.

Mulberry (Morus Alba L., family Moraceae) leaf extracts have various biological effects including inhibition of oxidative modification of low-density lipoprotein (LDL), which is the major cause of atherosclerosis. Endothelial dysfunction elicited by oxidized LDL (Ox-LDL) has been implicated in atherogenesis. Lectin-like Ox-LDL receptor-1 (LOX-1), a cell-surface receptor for atherogenic Ox-LDL, appears to mediate Ox-LDL-induced inflammation, which may be crucial in atherogenesis. Previous studies revealed that expression of LOX-1 is highly inducible by proinflammatory stimuli, including tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), and transforming growth factor-beta (TGF-beta). Therefore, we examined whether mulberry leaf aqueous fractions inhibit LOX-1 expression induced by proinflammatory stimuli. Pretreatment of cultured bovine aortic endothelial cells (BAECs) with mulberry leaf aqueous fractions inhibited TNF-alpha- and LPS-induced expression of LOX-1 at both protein and mRNA levels in a time- and concentration-dependent manner. In contrast, mulberry leaf aqueous fractions did not affect TGF-beta-induced LOX-1 expression. Furthermore, mulberry leaf aqueous fractions inhibited TNF-alpha-induced activation of nuclear factor-kappaB (NF-kappaB) and phosphorylation of inhibitory factor of NF-kappaB-alpha (IkappaB-alpha) in a time- and concentration-dependent fashion. Thus, mulberry leaf aqueous fractions suppress TNF-alpha- and LPS-induced LOX-1 gene expression, by inhibiting NF-kappaB activation.

Animals↗
PubMed2006

A case of metastatic testicular cancer complicated by tumour lysis syndrome and choriocarcinoma syndrome.

A 26-year-old man was referred to our hospital for treatment of metastatic testicular cancer. The pathological diagnosis was choriocarcinoma with seminoma. Sequential computerized tomography examinations revealed rapidly progressing bulky liver metastases and a lung metastasis. Chemotherapy with bleomycin, etoposide and cisplatin (BEP) was started on the day of admission. Subsequently, the patient suffered from tumour lysis syndrome (TLS) and massive haemorrhage at metastatic sites. The latter complication is also called choriocarcinoma syndrome. To our knowledge, this is the first case report of testicular cancer complicated with both critical conditions. Intensive care and radiological intervention barely prevented a fatal outcome. The urological oncologist should be aware of the potential complications TLS and choriocarcinoma syndrome in cases of rapidly progressive and high-volume choriocarcinoma.

Adult↗
PubMed2006

Rapid degradation of Bim by the ubiquitin-proteasome pathway mediates short-term ischemic tolerance in cultured neurons.

A previous exposure to a non-harmful ischemic insult (preconditioning) protects the brain against subsequent harmful ischemia (ischemic tolerance). In contrast to delayed gene-mediated ischemic tolerance, little is known about the molecular mechanisms that regulate rapid ischemic tolerance, which occurs within 1 h following preconditioning. Here we have investigated the degradation of the pro-apoptotic Bcl-2 family member Bim as a mechanism of rapid ischemic tolerance. Bim protein levels were reduced 1 h following preconditioning and occurred concurrent with an increase in Bim ubiquitination. Ubiquitinated proteins are degraded by the proteasome, and inhibition of the proteasome with MG132 (a proteasome inhibitor) prevented Bim degradation and blocked rapid ischemic tolerance. Inhibition of p42/p44 mitogen-activated protein kinase activation by U0126 reduced Bim ubiquitination and Bim degradation and blocked rapid ischemic tolerance. Finally, inhibition of Bim expression using antisense oligonucleotides also reduced cell death following ischemic challenge. Our results suggest that following preconditioning ischemia, Bim is rapidly degraded by the ubiquitin-proteasome system, resulting in rapid ischemic tolerance. This suggests that the rapid degradation of cell death-promoting proteins by the ubiquitin-proteasome pathway may represent a novel therapeutic strategy to reduce cell damage following neuropathological insults, e.g. stroke.

Animals↗
PubMed2006

Expression of lectin-like oxidized LDL receptor-1 in smooth muscle cells after vascular injury.

Lectin-like oxidized LDL receptor-1 (LOX-1) is an oxidized LDL receptor, and its role in restenosis after angioplasty remains unknown. We used a balloon-injury model of rabbit aorta, and reverse transcription-polymerase chain reaction revealed that LOX-1 mRNA expression was modest in the non-injured aorta, reached a peak level 2 days after injury, and remained elevated until 24 weeks after injury. Immunohistochemistry and in situ hybridization showed that LOX-1 was not detected in the media of non-injured aorta but expressed in both medial and neointimal smooth muscle cells (SMC) at 2 and 24 weeks after injury. Low concentrations of ox-LDL (10 microg/mL) stimulated the cultured SMC proliferation, which was inhibited by antisense oligonucleotides of LOX-1 mRNA. Double immunofluorescence staining showed the colocalization of LOX-1 and proliferating cell nuclear antigen in human restenotic lesion. These results suggest that LOX-1 mediates ox-LDL-induced SMC proliferation and plays a role in neointimal formation after vascular injury.

Animals↗
PubMed2006

Detection of hepatic metastases using ferucarbotran-enhanced MR imaging: feasibility and diagnostic accuracy of three-dimensional sensitivity-encoding water-excitation multishot echo-planar sequence (3D-SWEEP).

PURPOSE: To evaluate the diagnostic accuracy of a ferucarbotran-enhanced three-dimensional sensitivity-encoding water-excitation multishot echo-planar sequence (3D-SWEEP) for detecting hepatic metastases compared to a T2*-weighted fast field-echo (FFE) sequence. MATERIALS AND METHODS: Twenty-five consecutive patients with hepatic metastases underwent ferucarbotran-enhanced MRI on a 1.5-T unit before hepatic resections. Eighty-two foci of metastases were confirmed by histopathology or intraoperative ultrasonography (US). Signal-intensity decay (SID), tumor-to-liver contrast (TLC), and image quality were compared between T2*-weighted FFE and 3D-SWEEP. Three independent observers reviewed three imaging sets: set 1, without 3D-SWEEP or T2*-weighted FFE; set 2, with T2*-weighted FFE; and set 3, with 3D-SWEEP. The mean values of areas under alternative free response receiver operating characteristic curves (Az) and sensitivities were compared among the three sets. RESULTS: SID and TLC were significantly greater for 3D-SWEEP than T2*-weighted FFE, although 3D-SWEEP had poorer image quality. The mean Az and sensitivity were significantly greater for set 3 compared to set 1 for detecting overall lesions, and compared to sets 1 and 2 for detecting lesions of 1-2 cm in diameter. CONCLUSION: Despite relatively prominent artifacts, ferucarbotran-enhanced 3D-SWEEP was more sensitive and accurate than T2*-weighted FFE for detecting hepatic metastases.

Aged↗
PubMed2006

In vivo localized 1H MR spectroscopy of rat testes: stimulated echo acquisition mode (STEAM) combined with short TI inversion recovery (STIR) improves the detection of metabolite signals.

A noninvasive NMR technique for evaluating testicular function was explored in this study. Localized in vivo 1H NMR spectroscopy was performed on rat testes using a stimulated echo acquisition mode (STEAM) sequence with a short echo time (TE). In the 1H spectra, large lipid signals dominated the chemical shift range of 0.89-2.78 ppm, which prevented the observation of metabolite signals in this region. To suppress these lipid signals, short inversion time (TI) inversion recovery (STIR) was combined with STEAM (STIR-STEAM). The optimal TI was typically 320 ms. STIR-STEAM with a TE of 15 ms allowed successful suppression of the lipid signals and the sensitive detection of several new metabolite signals. In normal testes, choline, creatine, glutamate, and glycine signals were identified. In addition to these metabolites, a lactate signal was observed in ischemic testes. To our knowledge, the signals of glutamate, glycine, and lactate have not been previously assigned in 1H MR spectra of testes in vivo. Lipid suppression by STIR aided in the detection of these metabolites, which would otherwise have been masked by the lipid signals.

Animals↗
PubMed2006

Detection of intraductal component around invasive breast cancer using ultrasound: correlation with MRI and histopathological findings.

PURPOSE: The purpose of this study was preoperatively to diagnose the intraductal component, which is indispensable in planning for breast conservation therapy, and also to minimize local recurrence. This study investigated the efficacy of ultrasound (US) in the detection of intraductal component in comparison with magnetic resonance imaging (MRI) and histopathological findings. PATIENTS AND METHODS: In 47 patients with invasive breast cancer, US features of the intraductal component were classified as (a) solid ductal dilatation radiating from the tumor, (b) presence of satellite lesion in the same segment without ductal dilatation, and (c) ductal dilatation between the main tumor and satellite lesion. MRI depicted intraductal extension as the most enhanced area during the first or second phase of the dynamic study. Other criteria for the detection of the intraductal component by MRI were as follows: (a) a satellite lesion around the main tumor, (b) bridging enhancement between the main tumor and satellite lesions. The extent of the intraductal component was measured and classified as mimimal (0-5 mm), moderate (6-15 mm) or wide (>15 mm). RESULTS: In 28 of 47 (60.0%) patients, a wide intraductal component of more than 15 mm was proved histopathologically. Of 28 patients, US and MRI could accurately detect wide intraductal components in 16 patients and 14 patients, respectively. Sensitivity, specificity, and accuracy were 57.1%, 84.2%, and 68.1% respectively for US and 50.0%, 89.5% and 65.9% for MRI, respectively. When both US and MRI results were combined, sensitivity, specificity, and accuracy were 75.0%, 84.2%, and 78.7%. CONCLUSION: Current US examination depicted the intraductal component of breast cancer more accurately than MRI. Further, our study suggests that the use of both US and MRI together is complementary and offers more advantage than US alone.

Adult↗
PubMed2006

Trends in oncological CT imaging: clinical application of multidetector-row CT and 3D-CT imaging.

Computed tomography (CT) plays an essential role in oncological imaging as the modality of screening for malignancies, mapping out the treatment strategy at staging, assessing response to the treatment, and following up patient outcome after the treatment. The advent of multidetector-row CT (MDCT) has brought about dramatic changes in clinical oncological imaging. The very superior temporal and spatial resolution of MDCT has transformed CT imaging from a transaxial cross-sectional technique into an isotropic volume-imaging technique. MDCT facilitates multiphasic contrast-enhanced study for a wide range of body scanning in a single examination, as well as providing flexibility of multidirectional reconstruction and high-quality three-dimensional imaging. With increases in the number of detector rows year by year, systems with 64-detector rows have become commercially available in 2006. The purpose of this article is to review the status of CT imaging in oncological imaging: (1) to outline the impact of MDCT, focusing on oncological imaging and (2) to review the clinical applications of oncological CT imaging with MDCT.

Humans↗
PubMed2006

Perfusion-weighted magnetic resonance imaging of the spinal cord in cervical spondylotic myelopathy.

Principles of echo shifting with a train of observations was used to perform magnetic susceptibility-weighted magnetic resonance imaging with bolus-tracking in 14 patients with spondylotic myelopathy to assess changes in perfusion parameters of the spinal cord before and after decompression surgery for cervical spondylotic myelopathy. The mean transit time (MTT), bolus arrival time (T0), and time to peak (TTP) were obtained from regions of interest (ROIs) and assessed as the ratio between the spinal cord and the pons (MTT index = MTT(ROI)/MTT(pons), T0 index = T0(ROI)/T0(pons), TTP index = TTP(ROI)/TTP(pons)). The patients were divided into two groups according to percentage improvement on the Neurosurgical Cervical Spine Scale. The MTT index in patients with good recovery (> or =50%) was significantly reduced. The T0 index and TTP index showed no significant change in both groups. Reduction of MTT index may indicate improved perfusion of the spinal cord following surgery for cervical spondylotic myelopathy.

Aged↗
PubMed2005

Efficacy of spectral presaturation of inversion recovery in evaluating delayed myocardial enhancement.

OBJECTIVE: Delayed myocardial enhancement is caused by a variety of cardiovascular diseases. The extent of the enhanced area has been examined by the inversion recovery (IR) method, whereby at the inversion time (TI), normal myocardium shows a low signal intensity. In this sequence, as pericardial fat shows a very high intensity, a delayed enhancement just below the pericardium may be indistinct. To improve the accuracy of delayed myocardial enhancement, we employed the spectral presaturation of inversion recovery (SPIR) method. MATERIALS AND METHODS: Thirty-five patients with symptoms of cardiovascular disease aged between 36 and 80 years old (mean age, 62 years old) were investigated. Thirty were men and five were women. Inversion recovery and SPIR images were obtained 25 min after initial administration of a gadolinium-based contrast material. Each TI, when the signal intensity of the normal myocardium was null, was determined by images obtained at serial different TIs. A radiologist and a cardiologist examined each image by a consensus reading. The extent of myocardial enhancement was described as none, subendocardial, transmural and a random pattern in each case. Images were ranked over three levels and were based on whether myocardial enhancement could be easily detected or whether the contour of the myocardium was visualized precisely. Student's t-test was conducted to compare the quality of two sequences in all patients and in 22 patients who showed delayed myocardial enhancement. RESULTS: The imaging quality in evaluating delayed myocardial enhancement in all patients was superior with IR compared with SPIR, although it was not statistically significant. The imaging quality in the patients with delayed myocardial enhancement was similar between SPIR and IR. SPIR was superior to the IR sequence in two of the four patients who exhibited transmural enhancement. CONCLUSION: SPIR exhibited equivalent image quality to IR in evaluating delayed myocardial enhancement. As it has the potential advantage in patients with rich adipose tissue surrounding the myocardium, it can be an alternative sequence to evaluate myocardial viability.

Adult↗
PubMed2005

Serum soluble lectin-like oxidized low-density lipoprotein receptor-1 levels are elevated in acute coronary syndrome: a novel marker for early diagnosis.

BACKGROUND: Markers of cardiac injury, including troponin-T (TnT), are used to diagnose acute coronary syndrome (ACS); however, markers for plaque instability may be more useful for diagnosing ACS at the earliest stage. Lectin-like oxidized LDL receptor-1 (LOX-1) appears to play crucial roles in the pathogenesis of atherosclerotic plaque rupture and ACS onset. LOX-1 is released in part as soluble LOX-1 (sLOX-1) by proteolytic cleavage. METHODS AND RESULTS: We examined serum sLOX-1 levels in 521 patients, consisting of 427 consecutive patients undergoing coronary angiography, including 80 ACS patients, 173 symptomatic coronary heart disease patients, 122 patients with significant coronary stenosis without ischemia, and 52 patients without apparent coronary atherosclerosis plus 34 patients with noncardiac acute illness and 60 patients with noncardiac chronic illness. Time-dependent changes in sLOX-1 and TnT levels were analyzed in an additional 40 ACS patients. Serum sLOX-1 levels were significantly higher in ACS than the other groups and were associated with ACS as shown by multivariable logistic regression analyses. Given a cutoff value of 1.0 ng/mL, sLOX-1 can discriminate ACS from other groups with 81% and 75% of sensitivity and specificity, respectively. sLOX-1 can also discriminate ACS without ST elevation or abnormal Q waves and ACS without TnT elevation from non-ACS with 91% and 83% of sensitivity, respectively. Peak values of sLOX-1 in ACS were observed earlier than those of TnT. CONCLUSIONS: sLOX-1 appears to be a useful marker for early diagnosis of ACS.

Acute Disease↗
PubMed2005

Neuroprotection by osteopontin in stroke.

Osteopontin (OPN) is a secreted extracellular phosphoprotein involved in diverse biologic functions, including inflammation, cell migration, and antiapoptotic processes. Here we investigate the neuroprotective potential of OPN to reduce cell death using both in vitro and in vivo models of ischemia. We show that incubation of cortical neuron cultures with OPN protects against cell death from oxygen and glucose deprivation. The effect of OPN depends on the Arg-Gly-Asp (RGD)-containing motif as the protective effect of OPN in vitro was blocked by an RGD-containing hexapeptide, which prevents integrin receptors binding to their ligands. Osteopontin treatment of cortical neuron cultures caused an increase in Akt and p42/p44 MAPK phosphorylation, which is consistent with OPN-inducing neuroprotection via the activation of these protein kinases. Indeed, the protective effect of OPN was reduced by inhibiting the activation of Akt and p42/p44 MAPK using LY294002 and U0126, respectively. The protective effect of OPN was also blocked by the protein synthesis inhibitor cycloheximide, suggesting that the neuroprotective effect of OPN required new protein synthesis. Finally, intracerebral ventricular administration of OPN caused a marked reduction in infarct size after transient middle cerebral artery occlusion in a murine stroke model. These data suggest that OPN is a potent neuroprotectant against ischemic injury.

Animals↗
PubMed2005

CREB-mediated Bcl-2 protein expression after ischemic preconditioning.

Bcl-2 plays a pivotal role in the control of cell death and is upregulated by ischemic tolerance. Because Bcl-2 expression is regulated by the transcription factor cyclic AMP response element-binding protein (CREB), we investigated the role of CREB activation in two models of ischemic preconditioning: focal ischemic tolerance after middle cerebral artery occlusion (MCAO) and in vitro ischemic tolerance modeled by oxygen-glucose deprivation (OGD). After preconditioning ischemia (30 minutes MCAO or 30 minutes OGD), phosphorylation of CREB was increased, and there was an increased interaction between the bcl-2 cyclic AMP-responsive element (CRE) promoter and nuclear proteins after preconditioning ischemia in vivo and in vitro. Chromatin immunoprecipitation revealed an increased interaction between CREB-binding protein and the bcl-2 CRE rather than CREB, after preconditioning ischemia. Ischemic tolerance was blocked by a CRE decoy oligonucleotide, which also blocked Bcl-2 expression. The protein kinase A inhibitor H89, the calcium/calmodulin kinase inhibitor KN62, and the MEK inhibitor U0126 blocked ischemic tolerance, but not the phosphatidylinositol 3-kinase inhibitor LY294002. H89, KN62, and U0126 reduced CREB activation and Bcl-2 expression. Taken together, these data suggest that after ischemic preconditioning CREB activation regulates the expression of the prosurvival protein Bcl-2.

Animals↗
PubMed2004

Different mechanisms involved in interhemispheric transfer of visuomotor information.

Twenty-one subjects underwent event-related fMRI while carrying out a simple visuomotor task in which they responded to stimuli flashed either onto the right visual field, onto the left visual field, or onto both visual fields at once. The aim of this study was to clarify areas of brain activity associated with crossed-uncrossed differences (CUD) and to investigate differences of the brain activity between CUD and redundancy gain. An intriguing brain activation related to CUD was found in the genu of the corpus callosum (CC). The sites of activation related to redundancy gain were the extrastriate cortex and the cingulate cortex. Our results suggested that CUD depended on the interhemispheric transfer via the CC, and that CUD and redundancy gain involved different brain mechanisms.

Adult↗
PubMed2004

Peroxisome proliferator-activated receptor alpha ligands activate transcription of lectin-like oxidized low density lipoprotein receptor-1 gene through GC box motif.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a receptor for oxidized LDL. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors regulating transcription of various genes. We examined effects of PPAR ligands on LOX-1 expression and their transcriptional regulation in vascular endothelial cells. PPARalpha-specific ligands, such as fenofibrate and WY-14643, but not PPARgamma-specific ligands induced LOX-1 expression. Reduced expression of PPARalpha by antisense oligonucleotides directed to PPARalpha blocked fenofibrate-induced LOX-1 expression. Luciferase reporter gene assays with deletion and point mutations in the LOX-1 promoter revealed that transcriptional activity of LOX-1 gene by fenofibrate was localized in the -114/-106 GC box. Electrophoretic mobility shift assays with the radiolabeled GC box sequence showed inducible bands by PPARalpha ligands, which is competitively suppressed by unlabeled GC box motif and by an antibody to PPARalpha. In conclusion, PPARalpha appears to be one of the key regulators that induce LOX-1 expression, utilizing the GC box as a promoter.

Animals↗
PubMed2004

Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels.

Ca2+ toxicity remains the central focus of ischemic brain injury. The mechanism by which toxic Ca2+ loading of cells occurs in the ischemic brain has become less clear as multiple human trials of glutamate antagonists have failed to show effective neuroprotection in stroke. Acidosis is a common feature of ischemia and is assumed to play a critical role in brain injury; however, the mechanism(s) remain ill defined. Here, we show that acidosis activates Ca2+ -permeable acid-sensing ion channels (ASICs), inducing glutamate receptor-independent, Ca2+ -dependent, neuronal injury inhibited by ASIC blockers. Cells lacking endogenous ASICs are resistant to acid injury, while transfection of Ca2+ -permeable ASIC1a establishes sensitivity. In focal ischemia, intracerebroventricular injection of ASIC1a blockers or knockout of the ASIC1a gene protects the brain from ischemic injury and does so more potently than glutamate antagonism. Thus, acidosis injures the brain via membrane receptor-based mechanisms with resultant toxicity of [Ca2+]i, disclosing new potential therapeutic targets for stroke.

Acid Sensing Ion Channels↗
PubMed2004

Endotoxin preconditioning prevents cellular inflammatory response during ischemic neuroprotection in mice.

BACKGROUND AND PURPOSE: Tolerance to ischemic brain injury is induced by several preconditioning stimuli, including lipopolysaccharide (LPS). A small dose of LPS given systemically confers ischemic protection in the brain, a process that appears to involve activation of an inflammatory response before ischemia. We postulated that LPS preconditioning modulates the cellular inflammatory response after cerebral ischemia, resulting in neuroprotection. METHODS: Mice were treated with LPS (0.2 mg/kg) 48 hours before ischemia induced by transient middle cerebral artery occlusion (MCAO). The infarct was measured by 2,3,5-triphenyltetrazolium chloride staining. Microglia/macrophage responses after MCAO were assessed by immunofluorescence and flow cytometry. The effect of MCAO on white blood cells in the brain and peripheral circulation was measured by flow cytometry 48 hours after MCAO. RESULTS: LPS preconditioning induced significant neuroprotection against MCAO. Administration of low-dose LPS before MCAO prevented the cellular inflammatory response in the brain and blood. Specifically, LPS preconditioning suppressed neutrophil infiltration into the brain and microglia/macrophage activation in the ischemic hemisphere, which was paralleled by suppressed monocyte activation in the peripheral blood. CONCLUSIONS: LPS preconditioning induces neuroprotection against ischemic brain injury in a mouse model of stroke. LPS preconditioning suppresses the cellular inflammatory response to ischemia in the brain and circulation. Diminished activation of cellular inflammatory responses that ordinarily exacerbate ischemic injury may contribute to neuroprotection induced by LPS preconditioning.

Animals↗