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Hiromichi Ito

Publications and source records attributed to Hiromichi Ito.

At least 19 recordsLinked to original sources
PubMed2006

A case of Kabuki syndrome presenting West syndrome.

A 6-month-old girl visited our hospital because of mental retardation, regression, and tonic spasms in cluster. We diagnosed her as West syndrome because of hypsarrhythmia on electroencephalogram (EEG) and tonic spasms in cluster. We also diagnosed her as Kabuki syndrome because of multiple malformations, especially a characteristic peculiar face (resembling a Kabuki actor). She was first administered clonazepam, but this was not effective. Later, she was administered vitamin B6, valproic acid, and zonisamide. Zonisamide was effective, and her tonic spasms were suppressed. Her EEG at 9 months of age showed the disappearance of hypsarrhythmia and sporadic spike and wave complexes on P3, P4, O1, and O2. At 2 years of age, she still showed mental retardation, despite the good control of West syndrome. To the best of our knowledge, Kabuki syndrome presenting West syndrome has been reported in only one previous case. We must pay attention to the occurrence of West syndrome in Kabuki syndrome.

Abnormalities, Multiple↗
PubMed2006

Patients with West syndrome whose ictal SPECT showed focal cortical hyperperfusion.

To clarify the mechanism of clustered spasms in West syndrome (WS), we examined ictal SPECT and EEG, as well as those during the interictal period, in three patients with symptomatic WS who had apparent focal cerebral lesions. For ictal SPECT and EEG, we monitored the patients with EEG, and as soon as we noticed the occurrence of clustered spasms clinically and electroencephalographically, [(99m)Tc]ECD was injected intravenously and flushed thoroughly with saline. In these three patients, regional cerebral blood flow (rCBF) increased during ictus and decreased during the interictal period in the area that coincided with the focal cerebral lesion recognized by CT/MRI. The ictal hyperperfusion of bilateral basal ganglia was also detected in two of the three patients. The ictal EEG showed a diffuse slow wave complex corresponding to a clinical spasm. The sharp waves that preceded the diffuse slow wave complex and the spasm appeared in the same area in which rCBF increased during ictus. None of the patients showed partial seizure before or after clustered spasms clinically or electroencephalographically during the ictal SPECT study. Secondary generalization from a cerebral focus may explain the mechanism of spasms in these patients with WS: focal cortical discharge may primarily generate clustered spasms and trigger the brainstem and basal ganglia structures to produce spasms.

Cerebral Cortex↗
PubMed2006

Favorable response of ADHD with giant SEP to extended-release valproate.

We treated three boys with attention deficit/hyperactivity disorder (ADHD) associated with giant somatosensory evoked potentials (SEP). All responded well to extended-release valproate (EVA), a gamma-aminobutyric acid (GABA) enhancer. Improvement particularly involved hyperactivity and impulsivity. When methylphenidate previously was administered to two patients, symptoms worsened. EVA therefore may be preferable for ADHD with giant SEP.

Adolescent↗
PubMed2006

Carcinomatous meningitis from non-small-cell lung cancer responding to gefitinib.

The prognosis for carcinomatous meningitis remains poor, and focal neurological dysfunctions usually do not improve despite the available treatment options. We report a case of carcinomatous meningitis from non-small-cell lung cancer treated with gefitinib, which brought about a sustained clinical response. A 40-year-old Japanese man was diagnosed with adenocarcinoma in the right lower lobe of the lung, and with multiple pulmonary and brain metastases. Six courses of carboplatin and paclitaxel chemotherapy and gamma-knife radiosurgery induced a near complete response in all lesions. However, 2 months later, cauda equina syndrome and left oculomotor paralysis from carcinomatous meningitis developed rapidly. Magnetic resonance imaging of the brain and spinal cord revealed the enhancement of leptomeningeal disseminations. The patient was treated with 250 mg/day gefitinib. All his neurological symptomatology disappeared within 2 weeks. The shrinkage of the leptomeningeal disseminations was confirmed by follow-up magnetic resonance imaging. The patient is currently doing well and is able to work. Cancer relapse was not observed at 4 months after the initiation of gefitinib. Although the survival benefit is controversial, gefitinib may have a role in the treatment of carcinomatous meningitis from non-small-cell lung cancer to improve neurological dysfunctions.

Adult↗
PubMed2005

RNA interference demonstrates a novel role for integrin-linked kinase as a determinant of pancreatic adenocarcinoma cell gemcitabine chemoresistance.

Integrin-linked kinase (ILK) facilitates signal transduction between extracellular events and important intracellular survival pathways involving protein kinase B/Akt. We examined the role of ILK in determining pancreatic adenocarcinoma cellular chemoresistance to the nucleoside analogue gemcitabine. Cellular ILK expression was quantified by Western blot analysis. We examined the effects of overexpression of active ILK and of ILK knockdown induced by RNA interference on gemcitabine chemoresistance. We also examined the effects of modulating ILK expression on gemcitabine-induced caspase 3-mediated apoptosis, phosphorylation status of Akt (Ser473) and glycogen synthase kinase. Overexpression of ILK increased cellular gemcitabine chemoresistance, whereas ILK knockdown induced chemosensitization via increased caspase 3-mediated apoptosis. ILK knockdown attenuated Akt Ser473 and glycogen synthase kinase phosphorylation, whereas overexpression of constitutively active myristoylated Akt was sufficient to induce significant recovery in gemcitabine chemoresistance in the presence of ILK knockdown. Levels of ILK expression affect gemcitabine chemoresistance in pancreatic adenocarcinoma cells. This novel finding suggests that therapies directed against ILK and its downstream signaling targets may have the potential to enhance the efficacy of gemcitabine-based chemotherapy.

Adenocarcinoma↗
PubMed2005

Risk factors and outcomes of pancreatitis after open heart surgery.

BACKGROUND: We sought to analyze the risk factors and natural history associated with post-cardiac surgery acute pancreatitis. METHODS: Retrospective analysis of all patients having undergone cardiac surgery at our hospital between January 1, 1992, and October 1, 2001. RESULTS: A total of 10,249 cardiac operations were performed. Thirty-nine (0.4%) patients developed postoperative pancreatitis. There was a higher incidence during the period spanning 1992 through 1996 than 1997 through 2001 (0.6% versus 0.2%, P< .05). Patients with pancreatitis had longer postoperative length of stay (51+/-5 days versus 10+/-1 days, P<.05) and a greater in-hospital mortality rate (28% versus 4%, P<.05) than patients who did not develop pancreatitis. A history of alcohol abuse, cardiac surgery performed during 1992 to 1996, increased cardiopulmonary bypass time, and increased cross-clamp time were independent risk factors for the development of pancreatitis. Multiple-organ failure was an independent predictor for death among patients with pancreatitis. CONCLUSIONS: Although the frequency of post-cardiac surgery pancreatitis is diminishing, it is still associated with significant mortality.

Acute Disease↗
PubMed2005

A case of acute encephalitis with refractory, repetitive partial seizures, presenting autoantibody to glutamate receptor Gluepsilon2.

An 11-year-old male was admitted to our hospital because of high-grade fever, repetitive seizures, and prolonged impairment of consciousness (Glasgow coma scale E1, M5, V1). His seizures were repetitive complex partial seizures that expanded from the unilateral face to the corresponding side of the body. He sometimes developed secondary generalized seizures. While most seizures lasted 1 or 2 min, intractable seizures also frequently (about 5 times/h) occurred. We diagnosed him as encephalitis/encephalopathy, and treated him with artificial respiration, thiamylal sodium, mild hypothermia therapy, steroid pulse therapy, massive gamma-globulin therapy, etc. Afterwards, he had sequelae, such as post-encephalitic epilepsy (same seizures continued to recur), hyperkinesia, impairment of immediate memory, change in character (he became sunny and obstinate), dysgraphia, and mild atrophy of the hippocampus, amygdala, and cerebrum. However, he could still attend a general junior high school. He was diagnosed as acute encephalitis with refractory, repetitive partial seizures (AERRPS). In this case, he was positive for autoantibody to glutamate receptor Gluepsilon2 IgG or IgM in an examination of blood and spinal fluid, and we presumed that this may have influenced his sequelae. In this case, a combination of mild hypothermia therapy, steroid pulse therapy, and massive gamma-globulin therapy was effective.

Autoantibodies↗
PubMed2005

Findings of brain 99mTc-ECD SPECT in high-functioning autism--3-dimensional stereotactic ROI template analysis of brain SPECT.

The aim of this study is confirmation of an abnormal regional cerebral blood flow (rCBF) pattern in high-functioning autism (HFA). Confirmation of an abnormal rCBF pattern in HFA may be useful for elucidate of its pathophysiology and a differential diagnosis, such as with attention-deficit/hyperactivity disorder (AD/HD). Brain 99mTc-ECD SPECT was performed in 16 cases of HFA. The HFA group consisted of 16 cases of HFA. They were all male, with an IQ of 76-126. They had normal brain MRI findings, and had an age of 9-14 years. We examined abnormal rCBF in HFA by comparing the results to those in the control group. The control group consisted of 1 male and 4 females cryptogenic epilepsy patients with normal intelligence. They have no problems in learning at school or mental or behavioral traits. They had normal brain MRI or SPECT findings, and had an age of 7-15 years. 3-dimensional stereotactic ROI template (3DSRT) was used to analyze SPECT data. We calculated the 'relative rCBF (%)' (RI count of each segment x 100/Sum of RI count of the corresponding hemisphere), and compared the values between the two groups. We found a significantly low 'relative rCBF (%)' in the left temporal region in the HFA group. We also calculated the 'L/R ratio' (the 'relative rCBF (%)' of a segment on the left side / the 'relative rCBF (%)' of the corresponding segment on the right side), and compared the value for each segment between the two groups. There were no significant differences in any segments between the two groups. We also checked for differences in the 'relative rCBF (%)' between segments on the right side and corresponding segments on the left side in both the HFA and control groups. We found significant right < left perfusion in the angular region and significant left < right perfusion in the pericallosal, thalamus, and hippocampus region in the HFA group. We also found significant right < left perfusion in the temporal region in the control group. Significant hypoperfusion in the left temporal region due to an unidentified underlying brain pathology and abnormal laterality in the angular, temporal (lack of right < left perfusion), pericallosal, thalamus, and hippocampus regions may influence the symptoms of autism.

Adolescent↗
PubMed2005

[Autistic disorders].

Autism is a syndrome that consists of disturbances in social interactions, communication and imagination, and its first-choice of therapy is education. Of special interest is the period of the onset and early diagnosis of autism, and its relation to the period of intervention. In retrospective studies from questionnaire and home videotape analysis, it has been reported that autistic children display significantly less social interaction, joint attention behavior and communicative behavior compared to typical children, before 12 to 18 months of age. Although there is less evidence of a marked reduction in autistic symptomatology, early intervention studies have been found to have positive effects with significant improvements being reported in social behavior, self care, and academic skill. However, early interventions are controversial. We discuss early diagnosis and interventions in children with autism in this paper.

Autistic Disorder↗
PubMed2004

RETRACTED: Prostaglandin E2 enhances pancreatic cancer invasiveness through an Ets-1-dependent induction of matrix metalloproteinase-2.

Accumulating evidence suggests an important role for cyclooxygenase-2 (COX-2) in the pathogenesis of a wide range of malignancies. Here we tested the hypothesis that the COX-2 product prostaglandin E(2) (PGE(2)) increases cellular invasive potential by inducing matrix metalloproteinase-2 (MMP-2) expression and activity through an extracellular signal-regulated kinase (ERK)/Ets-1-dependent mechanism in pancreatic cancer. PANC-1 and MIAPaCa-2 pancreatic cancer cells were treated with PGE(2) or rofecoxib, a selective COX-2 inhibitor. MMP-2 expression and activity were assayed using Western blot analysis and zymography, respectively. MMP-2 promoter activity was analyzed with a luciferase-based assay. Ets-1 activity was analyzed using gel shift assay. Ets-1 expression was specifically silenced using RNA interference. Cellular invasive and migratory potentials were determined using a Boyden chamber assay with or without Matrigel, respectively. Exogenous PGE(2) induced MMP-2 expression and activity and increased ERK1/2 phosphorylation, Ets-1 binding activity, and MMP-2 promoter activity. PGE(2) also increased cellular migratory and invasive potentials. The mitogen-activated protein kinase kinase inhibitor PD98059 and Ets-1 silencing each abolished PGE(2)-induced increases in MMP-2 expression. PD98059 and Ets-1 silencing each abrogated the effect of PGE(2) on cellular invasive potential but not on cellular migratory potential. Rofecoxib suppressed MMP-2 expression and activity, Ets-1 binding activity, MMP-2 promoter activity, and cellular migratory and invasive potentials. These results suggest that PGE(2) mediates pancreatic cancer cellular invasiveness through an ERK/Ets-1-dependent induction of MMP-2 expression and activity. They also suggest that COX-2 inhibition may represent a strategy to inhibit invasive potential in pancreatic cancer.

Cell Line, Tumor↗
PubMed2004

Ligation of EphA2 by Ephrin A1-Fc inhibits pancreatic adenocarcinoma cellular invasiveness.

The Eph tyrosine kinases interact with ligands of the Ephrin family and have diverse cellular functions. EphA2 has been recognized to be an oncoprotein of importance in a range of cancers. Here, we examine the effect of EphA2 overexpression and ligation by chimeric Ephrin A1-Fc on the invasive phenotype of pancreatic adenocarcinoma cells. We show that EphA2 overexpression induces a FAK-dependent increase in MMP-2 expression and invasiveness. EphA2 ligation induces proteosomal degradation of EphA2, attenuates the invasive phenotype, and decreases both FAK phosphorylation and MMP-2 expression. EphA2 appears to represent a rational therapeutic target and ligation by Ephrin A1-Fc is one strategy to modulate levels of this oncoprotein.

Adenocarcinoma↗
PubMed2004

Overexpression of CEACAM6 promotes insulin-like growth factor I-induced pancreatic adenocarcinoma cellular invasiveness.

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is a glycosylphosphatidylinositol-linked immunoglobulin superfamily member that is overexpressed in a variety of human cancers. We have recently reported that suppression of CEACAM6 expression impairs pancreatic adenocarcinoma progression in vivo. In order to characterize the mechanisms through which CEACAM6 influences the malignant phenotype, CEACAM6-overexpressing Capan2 pancreatic adenocarcinoma cells were established by stable transfection. We determined the effect of CEACAM6 overexpression on cellular invasiveness towards insulin-like growth factor I (IGF-I), a peptide of critical importance in pancreatic cancer malignant cellular behavior and tumor progression. IGF-I-induced cellular invasiveness and IGF-IR expression were significantly increased in clones overexpressing CEACAM6. Using inhibitory anti-IGF-IR antibody, a requirement for IGF-IR signaling in the enhanced invasiveness towards IGF-I induced by CEACAM6 overexpression was confirmed. CEACAM6-overexpressing clones exhibited increased Akt and c-Src kinase activities, as well as higher levels of matrix metalloproteinase-2 (MMP-2) expression and activity in the presence of IGF-I. While Akt kinase is both necessary and sufficient to induce IGF-IR upregulation, c-Src kinase activity is necessary, but alone is insufficient to upregulate IGF-IR expression. CEACAM6 is an important determinant of pancreatic adenocarcinoma malignant cellular behavior and, together with its downstream targets, warrants further investigation as a therapeutic target in this disease.

Adenocarcinoma↗
PubMed2004

A novel role for carcinoembryonic antigen-related cell adhesion molecule 6 as a determinant of gemcitabine chemoresistance in pancreatic adenocarcinoma cells.

Most patients with pancreatic adenocarcinoma present with surgically incurable disease. Gemcitabine, the principal agent used to treat such patients, has little impact on outcome. Overexpression of carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 6, a feature of this malignancy, is associated with resistance to anoikis and increased metastasis. The purpose of this study was to determine the role of CEACAM6 in cellular chemoresistance to gemcitabine. CEACAM6 was stably overexpressed in Capan2 cells, which inherently express very low levels of the protein. Suppression of CEACAM6 expression was achieved in BxPC3 cells, which inherently overexpress CEACAM6, by stable transfection of a CEACAM6 small interfering RNA-generating vector. The effects of modulating CEACAM6 expression on gemcitabine-induced cytotoxicity were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxicity assay, flow cytometric apoptosis quantification, caspase profiling, and Western analysis of cytoplasmic cytochrome c release. The roles of Akt and c-Src kinases as downstream targets of CEACAM6 signaling were examined. Stable overexpression of CEACAM6 in Capan2 increased gemcitabine chemoresistance, whereas CEACAM6 gene silencing in BxPC3 markedly increased the sensitivity of these cells to gemcitabine. Differential expression of CEACAM6 modulates Akt activity in a c-Src-dependent manner, and CEACAM6 overexpression appears to protect cells from cytochrome c-induced caspase 3 activation and apoptosis.

Adenocarcinoma↗
PubMed2004

Fibronectin-induced COX-2 mediates MMP-2 expression and invasiveness of rhabdomyosarcoma.

Although accumulating evidence suggests the importance of cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)) in the pathogenesis of many cancers, the mechanism by which this enzyme and its metabolite promote cancer progression is unknown. In this study, we investigated the role of COX-2 in fibronectin-induced up-regulation of rhabdomyosarcoma matrix metalloproteinase (MMP)-2 activity and cellular invasiveness. We tested three human rhabdomyosarcoma cell lines: RMS559, RD, and SJRH30. Cell attachment to fibronectin up-regulated both COX-2 expression and PGE(2) production and concomitantly enhanced MMP-2 activity. Exogenous PGE(2) stimulated MMP-2 promoter activity, increased MMP-2 expression, and increased cellular invasiveness. Aspirin and rofecoxib (non-selective and selective COX-2 inhibitor, respectively) each abolished fibronectin-associated induction of MMP-2 and induced dose-dependent reductions in cellular invasiveness. These data implicated a role for inducible COX-2 and PGE(2) in the regulation of rhabdomyosarcoma cellular invasiveness and MMP-2 activity.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

CEACAM6 as a novel target for indirect type 1 immunotoxin-based therapy in pancreatic adenocarcinoma.

Immunotoxins are a potentially powerful approach for targeted anticancer therapy. We evaluated a novel immunotherapeutic strategy targeting the immunoglobulin superfamily member carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6). Using pancreatic adenocarcinoma as a model, we show that crosslinking CEACAM6 induces its cytoplasmic accumulation and that this effect can be utilized to increase the efficacy of antibody-mediated delivery of the ribosomal inhibitory protein saporin. Exposure of cells to anti-CEACAM6 antibody, followed by secondary saporin-conjugated immunoglobulin (IgG), induced marked cytotoxicity, via caspase-mediated apoptosis, in vitro. In an in vivo nude mouse xenograft model, this immunotherapeutic approach markedly suppressed pancreatic adenocarcinoma tumor growth and enhanced tumor apoptosis. Given the prevalence of CEACAM6 overexpression among human malignancies, immunological targeting of this tumor antigen may have therapeutic applicability.

Adenocarcinoma↗
PubMed2004

Lymphangiogenesis in tissue-engineered small intestine.

BACKGROUND: Lymphangiogenesis, the formation of lymphatic vessels, has not been reported in engineered tissue. The purpose of this study was to characterize lymphangiogenesis in tissue-engineered small intestine. METHODS: Biodegradable polymer scaffolds seeded with intestinal organoid units were implanted into syngenic recipient rats. Twenty-three neointestinal grafts were harvested from adult rat recipients 1 to 8 weeks postimplantation. Cells expressing the lymphatic endothelial marker vascular endothelial growth factor receptor (VEGFR)-3 were detected immunohistochemically. The lymphangiogenic growth factor VEGF-C was quantified by enzyme-linked immunoadsorbent assay. RESULTS: Between the first and eighth weeks, neointestinal cysts increased in volume and mass. Muscular and mucosal layers increased in thickness and developed to resemble normal intestine histologically. The proportion of neointestinal VEGFR-3-positive cells increased and ultimately, tubular structures developed that resembled lymphatics architecturally, were distinct from CD34-positive blood vessels, and lacked luminal erythrocytes. CONCLUSION: Lymphangiogenesis occurs in tissue-engineered small intestine. This is the first demonstration of lymphatic vessels in an engineered tissue.

Animals↗
PubMed2004

c-Src-dependent cross-talk between CEACAM6 and alphavbeta3 integrin enhances pancreatic adenocarcinoma cell adhesion to extracellular matrix components.

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is an immunoglobulin superfamily member with a diversity of extracellular ligands that is implicated in the initiation and progression of a variety of malignancies. We sought to characterize the effects of CEACAM6 crosslinking on pancreatic adenocarcinoma cellular interaction with the extracellular matrix (ECM) components fibronectin and vitronectin. Antibody-mediated CEACAM6 crosslinking was performed and the ability of BxPC3 cells, which inherently overexpress CEACAM6, to adhere to fibronectin and vitronectin was quantified. The roles of the archetypal fibronectin (alpha5beta1 integrin) and vitronectin (alphavbeta3 integrin) receptors were determined. The effects of c-Src inhibition were investigated using the Src family kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) and c-Src specific RNA interference. CEACAM6 crosslinking initiates c-Src-dependent cross-talk between CEACAM6 and alphavbeta3 integrin, leading to increased ECM component adhesion. CEACAM6-mediated signaling events may contribute to the invasive and metastatic potential of pancreatic adenocarcinoma cells by promoting their interaction with ECM components.

Adenocarcinoma↗