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Hiroshi Arai

Publications and source records attributed to Hiroshi Arai.

17 recordsLinked to original sources
PubMed2005

Expression of the adrenomedullin gene in adipose tissue.

Adrenomedullin (AM) is a potent vasodilating peptide originally isolated from human pheochromocytoma cells. This report concerns the expression and secretion of AM from adipose tissue. Northern blot analysis demonstrated marked expression of AM mRNA in mouse adipose tissue. Expression levels in adipose tissues were 2.5-3.2 times higher than in the kidney. AM mRNA level in mature adipocytes was 7.3 times higher than in the stroma-vascular fraction of adipose tissue. In mature adipocyte culture, time-dependent increase of AM peptide concentration in the culture medium was detected. AM expression was also detected in human subcutaneous adipose tissue. Adipose AM expression significantly increased in obesity mouse model, high-fat diet fed mice and ob/ob mice. These results suggest that adipose tissue, especially mature adipocytes, is major source of AM in the body, and that adipocyte-derived AM plays a pathophysiological role in obesity.

Adipocytes↗
PubMed2005

A case of type 2 diabetes mellitus developing hypothyroidism discovered as a result of a discrepancy between glycated hemoglobin and glycated albumin values.

We report a case of type 2 diabetes mellitus presenting hypothyroidism due to overeating of seaweed that was noticed as a result of a discrepancy between glycated albumin (GA) and glycated hemoglobin (GHb). A 71-year-old woman was undergoing managed treatment with oral medicines and insulin for diabetes mellitus with no sign of thyroid disease. Her thyroid function was euthyroid without aid of thyroid hormone. All of the patient's thyroid autoantibodies were negative. Fifteen weeks prior to indications of hypothyroidism, she had started to consume large amounts (100-200 g dry weight equivalent) of cooked "wakame" seaweed every morning. Just before admission to our hospital, her GA was 26.9%, while GHb and fasting plasma glucose remained within normal ranges (less than 5.6%, and 106 mg, respectively). This discrepancy between GA and GHb drew our attention to the development of complications. Naive interview of the patient led us to believe a thyroid hormone deficiency existed, though without any related complaints or findings, such as non-pitting edema, cold intolerance, or easy fatiguing. Seaweed consumption was stopped and periodic observation of thyroid function started. As thyroid hormone levels moved into normal range, GA and GHb returned to their normal relative ratio after 3 months. Thus, measurement of the relative ratio of GA and GHb may be useful for glycemic monitoring, with the potential as a readily available glycemic control marker for patients with changeable complications.

Aged↗
PubMed2005

Angiotensin II suppresses growth arrest specific homeobox (Gax) expression via redox-sensitive mitogen-activated protein kinase (MAPK).

Oxidative stress is known to be involved in growth control of vascular smooth muscle cells (VSMCs). We and others have demonstrated that angiotensin II (Ang II) has an important role in vascular remodeling. Several reports suggested that VSMC growth induced by Ang II was elicited by oxidative stress. Gax, growth arrest-specific homeobox is a homeobox gene expressed in the cardiovascular system. Over expression of Gax is demonstrated to inhibit VSMC growth. We previously reported that Ang II down-regulated Gax expression. To address the regulatory mechanism of Gax, we investigated the significance of oxidative stress in Ang II-induced suppression of Gax expression. We further examined the involvement of mitogen-activated protein kinases (MAPKs), which is crucial for cell growth and has shown to be activated by oxidative stress, on the regulation of Gax expression by Ang II. Ang II markedly augmented intracellular H2O2 production which was decreased by pretreatment with N-acetylcystein (NAC), an anti-oxidant. Ang II and H2O2 decreased Gax expression dose-dependently and these effects were blocked by administration of both NAC and pyrrolidine dithiocarbamate (PDTC), another anti-oxidant. Ang II and H2O2 induced marked activation of extracellular signal-responsive kinase1/2 (ERK1/2), which was blocked by NAC. Ang II and H2O2 also activated p38MAPK, and they were blocked by pre-treatment with NAC. However, the level of activated p38MAPK was quite low in comparison with ERK1/2. Ang II- or H2O2 -induced Gax down-regulation was significantly inhibited by PD98059, an ERK1/2 inhibitor but not SB203580, a p38MAPK inhibitor. The present results demonstrated the significance of regulation of Gax expression by redox-sensitive ERK1/2 activation.

Angiotensin II↗
PubMed2005

Complementary antagonistic actions between C-type natriuretic peptide and the MAPK pathway through FGFR-3 in ATDC5 cells.

We previously reported that C-type natriuretic peptide (CNP) stimulates endochondral ossification and corrects the reduction in body length of achondroplasia model mouse with constitutive active fibroblast growth factor receptor 3 (FGFR-3). In order to examine the interaction between CNP and FGFR-3, we studied intracellular signaling by using ATDC5 cells, a mouse chondrogenic cell line, and found that FGF2 and FGF18 markedly reduced CNP-dependent intracellular cGMP production, and that these effects were attenuated by MAPK inhibitors. Western blot analysis demonstrated that the level of GC-B, a particulate guanylyl cyclase specific for CNP, was not changed by treatment with FGFs. Conversely, CNP and 8-bromo-cGMP strongly and dose-dependently inhibited the induction of ERK phosphorylation by FGF2 and FGF18 without changing the level of FGFR-3, although they did not affect the phosphorylation of STAT-1. In the organ-cultured fetal mouse tibias, CNP and FGF18 counteracted on the longitudinal bone growth, and both the size and number of hypertrophic chondrocytes. The FGF/FGFR-3 pathway is known as the negative regulator of endochondral ossification. We found that FGFs inhibited CNP-stimulated cGMP production by disrupting the signaling pathway through GC-B while CNP antagonized the activation of the MAPK cascade by FGFs. These results suggest that the CNP/GC-B pathway plays an important role in growth plate chondrocytes and constitutes the negative cross talk between FGFs and the activity of MAPK. Our results may explain one of the molecular mechanisms of the growth stimulating action of CNP and suggest that activation of the CNP/GC-B pathway may be effective as a novel therapeutic strategy for achondroplasia.

Animals↗
PubMed2005

[Subfrontal schwannoma: case report].

Schwannoma are benign, slowly growing nerve sheath tumors. They can arise from any peripheral nerve containing Schwann cells including distal portions of cranial nerves. Intracranial schwannomas arising from a subfrontal lesion are very rare. We report a case of subfrontal schwannoma in a 38-year-old woman who presented with seizures in February 2003. MRI features resembled an olfactory groove meningioma. The left carotid angiography revealed that the tumor was supplied from the anterior ethomoidal artery, but no remarkable tumor stain was detected. Bifrontal craniotomy with total excision of the tumor revealed a tumor in the left subfrontal lesion. The tumor was attached to the falx, the left frontal lobe, and the skull base, but those structures were not invaded. Unfortunately, we could not detect the left olfactory nerve. Subsequent histological examination proved that this tumor was schwannoma. A review of the literature found 27 cases including this case previously described. Arguments are raised that schwannomas in a subfrontal lesion are comparable to or even occur as intracranial schwannomas with frontal localization. Subfrontal schwannomas are very rare. For this reason they have not been diagnosed preoperatively. Further cases of subfrontal schwannoma are necessary to solve the enigma of the origin of this tumor.

Adult↗
PubMed2004

Therapeutic potential of thiazolidinediones in activation of peroxisome proliferator-activated receptor gamma for monocyte recruitment and endothelial regeneration.

Thiazolidinediones, a new class of antidiabetic drugs that increase insulin sensitivity, have been shown to be ligands for peroxisome proliferator-activated receptor gamma (PPARgamma). Recent studies demonstrating that PPARgamma occurs in macrophages have focused attention on its role in macrophage functions. In this study, we investigated the effect of thiazolidinediones on monocyte proliferation and migration in vitro and the mechanisms involved. In addition, we examined the therapeutic potentials of thiazolidinediones for injured atherosclerotic lesions. Troglitazone and pioglitazone, the two thiazolidinediones, as well as 15-deoxy-delta12,14-prostaglandin J2 inhibited in a dose-dependent manner the serum-induced proliferation of THP-1 (human monocytic leukemia cells) and of U937 (human monoblastic leukemia cells), which permanently express PPARgamma. These ligands for PPARgamma also significantly inhibited migration of THP-1 induced by monocyte chemoattractant protein-1 (MCP-1). Troglitazone and 15-deoxy-delta12,14-prostaglandin J2 significantly suppressed the mRNA expression of the MCP family-specific receptor CCR2 (chemokine CCR2 receptor) in THP-1 at the transcriptional level. Furthermore, troglitazone significantly inhibited MCP-1 binding to THP-1. Oral administration of troglitazone to Watanabe heritable hyperlipidemic (WHHL) rabbits after balloon injury suppressed acute recruitment of monocytes/macrophages and accelerated re-endothelialization. These results suggest that thiazolidinediones have therapeutic potential for the treatment of diabetic vascular complications.

Alitretinoin↗
PubMed2003

Combined treatment with LDL-apheresis, chenodeoxycholic acid and HMG-CoA reductase inhibitor for cerebrotendinous xanthomatosis.

The effects of combined treatment with low-density lipoprotein (LDL)-apheresis, chenodeoxycholic acid (CDCA) and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor were studied in 2 patients with cerebrotendinous xanthomatosis. Patient 1 was initially treated with LDL-apheresis alone: serum cholestanol levels decreased by 50% after each apheresis, but returned to their initial levels within 2 weeks. After an addition of CDCA administration, the serum cholestanol levels steadily decreased, resulting in slight improvement of neurological symptoms. Patient 2 received a combined treatment with LDL-apheresis, CDCA and HMG-CoA reductase inhibitor. This combination showed less LDL-apheresis-dependent fluctuation and more rapid decrease of serum cholestanol levels than those in Patient 1, resulting in improvement and stabilization of the symptoms. Our results suggest that LDL-apheresis in combination with CDCA and HMG-CoA reductase inhibitor may have beneficial effects and can be one of the treatment options.

Adult↗
PubMed2003

Detection of amplified oncogenes by genome DNA microarrays in human primary esophageal squamous cell carcinoma: comparison with conventional comparative genomic hybridization analysis.

Oncogene amplification in 20 surgically resected esophageal squamous cell carcinomas (ESCC) was examined with DNA microarrays that detected 57 oncogenes and two reference DNA. Alterations in DNA copy numbers detected by microarrays were compared to those obtained by conventional comparative genomic hybridization (CGH). Amplification of eight oncogenes (CCND1, FGF3/FGF4, EMS1, SAS, ERBB2, PDGFRA, MYC, and BCL2) was detected by DNA microarrays in 9 of 20 tumors. Although ERBB2 was 23.2 times higher than the control level in one case, the average magnitude of gene amplification was approximately two to four times that of the control level. EMS1, CCND1, and FGF3/FGF4, which are all located on 11q13, were amplified in 7, 5, and 4 of 20 ESCC, respectively, and they were coamplified in 3 tumors. A comparison of genome DNA microarrays and CGH data revealed that although most amplified oncogenes were included in chromosomal regions for which DNA copy number gains were detected by conventional CGH, not all amplified genes on microarrays showed concomitant DNA copy number gains on CGH. In conclusion, microarrays of oncogenes are useful for the comprehensive identification of amplified oncogenes and for analysis of areas of specific amplification within chromosomal regions with DNA copy number increases detected by CGH analysis.

Aged↗
PubMed2003

Detection of gene amplification and deletion in high-grade gliomas using a genome DNA microarray (GenoSensor Array 300).

Glioblastoma is a rapidly growing tumor that accounts for more than 50% of all primary gliomas. Amplification of oncogenes and deletion of tumor suppressor genes frequently affects tumor progression. Thus, the goal of this study was to conduct a comprehensive analysis of gene aberrations of individual glioblastomas. A genome DNA microarray (GenoSensor Array 300), spotted with 287 target genes, was used to analyze resected tissue from 11 different high-grade gliomas. The average number of gene aberrations was 9.0 per case (WHO grade III) and 13.3 per case (WHO grade IV). EGFR was the most frequent amplified gene in this series (4 of 11 cases), and high-level amplification was also detected for EGFR, SAS/CDK4, and AKT1. A high frequency of deleted genes was observed in 6 of 11 cases (54.5%), including FGFR2, MTAP, and DMBT1. The detected gene aberrations were matched to the classical primary glioblastoma pathway in five of nine cases. We conclude that the GenoSensor Array 300 genomic DNA microarray is a useful method for the comprehensive identification of amplified and deleted genes in glioblastoma.

Adult↗
PubMed2003

A phase II study of radiotherapy after hyperbaric oxygenation combined with interferon-beta and nimustine hydrochloride to treat supratentorial malignant gliomas.

Hypoxic cells play a key role in the radioresistance of malignant glioma. Interferon-beta, ACNU as nimustine hydrochloride and radiotherapy (IAR) is a common therapy for malignant glioma in Japan. Since hyperbaric oxygenation (HBO) increases oxygen pressure in glioma tissue, we applied a modified IAR therapy, radiotherapy after HBO combined with interferon-beta and ACNU (HBO/IAR therapy), for supratentorial malignant gliomas. Daily radiation therapy was completed within 15 min after HBO. We assessed HBO/IAR with respect to toxicity, response rates and the time of tumor progression (TTP). We also examined the incidence of responses by some prognostic factors before HBO/IAR, namely, age, Karnofsky performance scale (KPS), histological type, tumor size, tumor site and operation type. Of 39 patients who participated in this study, 35 underwent a complete schedule of HBO/IAR therapy in which toxicity was permissible. Thirty patients (76.9%) either maintained or increased KPS during HBO/IAR with a mean duration of 68 +/- 14 days. The response rates (CR + PR%) for glioblastoma, anaplastic astrocytoma and overall were 50%, 30% and 43%, respectively. The incidence of therapeutic responses among all prognostic factors before HBO/IAR did not significantly differ. Median TTP for patients with glioblastoma, patients with anaplastic astrocytoma, and overall were 38, 56 and 43 weeks, respectively. The present study suggested that HBO/IAR therapy could be applied to especially patients with poor prognostic factors, because of its short treatment period, its permissible toxicity and identical response to patients with good prognostic factors.

Adult↗
PubMed2003

Measurement of fractional anisotropy using diffusion tensor MRI in supratentorial astrocytic tumors.

In vivo, water diffusion displays directionality due to presence of complex microstructural barriers in tissue. The extent of directionality of water diffusion can be expressed as a fractional anisotropy (FA) value, using diffusion tensor MR imaging (DTI). The aim of this study was to determine whether FA values indicate microstructures in astrocytic tumors. We performed DTI in 31 patients with astrocytic tumor, and measured the FA values of tumor and normal brain regions prior to CT-guided stereotactic biopsy. After biopsy, FA values were compared to assess the cellularity and vascularity of tumor tissue. Although mean FA values trended to differ among histological types, all mean tumor FA values were lower than those of normal brain regions. Positive correlation was observed between FA values and both cellularity (r = 0.65, p < 0.05) and vascularity (r = 0.45, p < 0.05). We had hypothesized that the FA value of an astrocytic tumor would be determined by a balance between factors increasing the directionality of water diffusion, such as high cellularity and/or vascularity, and factors decreasing the directionality of water diffusion, such as fiber destruction. However, our results suggest that the FA values of glioblastoma, anaplastic astrocytoma, diffuse astrocytoma and pilocytic astrocytoma are largely affected by cellularity and/or vascularity, whereas that of gliomatosis cerebri are largely affected by the preservation of nerve fibers. Measurement of FA value using DTI will allow prediction of histological characteristics such as cellularity, vascularity and/or fiber structure in astrocytic tumors.

Adult↗
PubMed2003

[Granulomatous change of the pituitary stalk caused by Rathke's cleft cyst: a case report].

We report a case of granulomatous change of the pituitary stalk caused by Rathke's cleft cyst. A 50-year-old woman complained of thirst and polyuria in December 2000. In January 2001, the patient was suspected to have diabetes inspidus, and MR Imaging showed a suprasellar mass of the pituitary stalk. The mass was totally resected by the trans-sylvian approach. Pathological diagnosis was Rathke's cleft cyst with subsequent granulomatous change. To our knowledge, there have been 11 cases of Rathke's cleft cyst and subsequent granulomatous change. In the literature, diabetes inspidus was not improved by surgical procedures. However, we suggest that the mass should be totally resected, because some cases in literature showed visual disturbance or hypo-pituitarism under observation.

Central Nervous System Cysts↗
PubMed2003

[Not Available].

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Journal Article↗
PubMed2002

Physiological concentration of atrial natriuretic peptide induces endothelial regeneration in vitro.

Both nitric oxide (NO) and natriuretic peptides produce apoptosis of vascular smooth muscle cells. However, there is evidence that NO induces endothelial cell proliferation, which suggests that there is a difference in the response of endothelial cells to natriuretic peptides. The purpose of this study was to investigate the effect of atrial natriuretic peptide (ANP) on human endothelial cell survival. ANP within the physiological concentration (10(-11) mol/l) induced a 52% increase in the number of human coronary arterial endothelial cells and a 63% increase in human umbilical vein endothelial cells at a low concentration of serum. The increase in cell numbers was blocked by pretreatment with RP8-CPT-cGMP (RP8), a cGMP-dependent protein kinase inhibitor, with wortmannin, an Akt/PKB inhibitor, and with PD-98059, an ERK1/2 inhibitor. In a Transwell migration test, ANP also increased the cell migration, and RP8, wortmannin, and PD-98059 blocked this increase. A wound healing assay was performed to examine the effects of ANP on regeneration in vitro. ANP increased both cell numbers and migration, but the effects were blocked by the above three kinase inhibitors. ANP increased the expression of phospho-Akt and of phospho-ERK1/2 within 1.5 h. These results suggest that ANP can potentiate endothelial regeneration by cGMP-dependent protein kinase stimulation and subsequent Akt and ERK1/2 activations.

Actins↗
PubMed2002

Change of oxygen pressure in glioblastoma tissue under various conditions.

Measurement of oxygen pressure (pO2) in tumor tissue is important, because pO2 is a major factor for radiosensitivity in malignant glioma treatment. We attempted to elucidate the changes in pO2 level in glioblastoma tissue of patients under various conditions. Eighteen patients with newly diagnosed glioblastoma were recruited to this study. Disposable Clark-type electrodes were inserted using CT guided stereotactic surgery under local anesthesia and left in the intra- and peritumoral regions. pO2 was measured in patients under conditions of being awake and asleep, inhaling 100% O2, being administered osmotic diuretics and following hyperbaric oxygen exposure (HBO). Peritumoral tissue had a significantly higher pO2 value in both awake and sleeping patients. O2 inhalation could not significantly increase the pO2 level, whereas administration of osmotic diuretics induced an increase in pO2 levels in peritumoral tissue alone. The pO2 levels were significantly increased in both regions after HBO, and a high pO2 level was maintained until 15 min after HBO in both regions. It is possible that the pO2 level in peritumoral tissue is affected by intracranial pressure, whereas that in the intratumoral tissue is usually low. HBO was the optimal procedure for oxygenation, but its benefit was reduced over time.

Administration, Inhalation↗