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Biomedical subjects

Hajime Arai

Publications and source records attributed to Hajime Arai.

At least 19 recordsLinked to original sources

Expression of TGF-betas and TGF-beta type II receptor in cerebrospinal fluid of patients with idiopathic normal pressure hydrocephalus.

We investigated cerebrospinal fluid (CSF) samples from 21 patients with idiopathic normal pressure hydrocephalus (INPH) and 14 controls without neurological disease. The concentrations of leucine-rich alpha-2-glycoprotein (LRG), transforming growth factor (TGF)-beta1, 2, 3 and TGF-beta type II receptor (TbetaR-II) in CSF were measured using ELISA. TGF-beta1, TbetaR-II and LRG CSF levels of patients with INPH were significantly higher than controls, whereas no significant differences in TGF-beta2 levels were found between INPH patients and controls. The present study suggests that TGF-betas expressions may be modulated differently in patients with INPH. These results also indicate that the CSF level assay of TGF-beta1, TbetaR-II and LRG is useful for the diagnosis of patients with INPH, and TGF-beta1, TbetaR-II and LRG may be involved in the pathogenesis of the disease.

Aged↗

Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: Curcumin is a biologically active phytochemical substance present in turmeric and has pharmacologic actions that might benefit patients with ulcerative colitis (UC). The aim in this trial was to assess the efficacy of curcumin as maintenance therapy in patients with quiescent ulcerative colitis (UC). METHODS: Eighty-nine patients with quiescent UC were recruited for this randomized, double-blind, multicenter trial of curcumin in the prevention of relapse. Forty-five patients received curcumin, 1g after breakfast and 1g after the evening meal, plus sulfasalazine (SZ) or mesalamine, and 44 patients received placebo plus SZ or mesalamine for 6 months. Clinical activity index (CAI) and endoscopic index (EI) were determined at entry, every 2 months (CAI), at the conclusion of 6-month trial, and at the end of 6-month follow-up. RESULTS: Seven patients were protocol violators. Of 43 patients who received curcumin, 2 relapsed during 6 months of therapy (4.65%), whereas 8 of 39 patients (20.51%) in the placebo group relapsed (P=.040). Recurrence rates evaluated on the basis of intention to treat showed significant difference between curcumin and placebo (P=.049). Furthermore, curcumin improved both CAI (P=.038) and EI (P=.0001), thus suppressing the morbidity associated with UC. A 6-month follow-up was done during which patients in both groups were on SZ or mesalamine. Eight additional patients in the curcumin group and 6 patients in the placebo group relapsed. CONCLUSIONS: Curcumin seems to be a promising and safe medication for maintaining remission in patients with quiescent UC. Further studies on curcumin should strengthen our findings.

Administration, Oral↗

Management of a suprasellar arachnoid cyst identified using prenatal sonography.

We present a rare case of suprasellar arachnoid cyst discovered incidentally on routine fetal sonographic examination. Serial sonographic and MRI scanning led to a prenatal diagnosis and appropriate endoscopic treatment at 5 months of age. The patient is currently developing normally at 3 years of age. Careful screening of fetal intracranial abnormalities is important in routine prenatal sonographic examination for early intervention, which will prevent irreversible complications such as endocrine disorders and visual impairment.

Adult↗

Late rapid deterioration after endoscopic third ventriculostomy: additional cases and review of the literature.

OBJECT: Late rapid deterioration after endoscopic third ventriculostomy (ETV) is a rare complication. The authors previously reported three deaths from three centers. Three other deaths and a patient who experienced rapid deterioration have also been reported. Following the death at the University of Toronto of an additional patient who underwent surgery elsewhere, they canvassed pediatric neurosurgeons in North America, Europe, Australia, and Asia for additional cases. METHODS: An email was sent to the members of the Canadian Congress of Neurological Sciences who are pediatric neurosurgeons, to the pediatric neurosurgery email list of the American Association of Neurological Surgeons, to the email list of the International Society for Pediatric Neurosurgery, and to designated neurosurgeons in the United Kingdom, France, Japan, Korea, Taiwan, and Australia, who in turn contacted pediatric neurosurgeons in their countries. A data form was provided, and data from previously reported cases were extracted. Nine additional cases were identified, and the results were collated with those of the seven cases previously reported. Patient age at surgery ranged from 2 days to 13 years (mean 7.6 years). The most common causes of hydrocephalus were aqueductal stenosis in 50% of patients and tectal glioma in 25% of patients. The time to treatment failure ranged from 5 weeks to 7.8 years (mean 2.5 years). Thirteen patients died, one patient was in a vegetative state, one patient was mildly disabled, and one patient whose condition deteriorated outside the operating room was alive and well. In the 13 patients in whom the ventriculostomy site was visualized at autopsy or repeated endoscopy, the ventriculostomy was shown to be occluded. CONCLUSIONS: Late rapid deterioration is a rare but lethal complication of ETV. The mechanism is unclear, but deterioration can occur long after the ETV becomes occluded. Patients and caregivers should be counseled regarding this potential complication. An indwelling ventricular access device is an option for patients undergoing ETV.

Adolescent↗

Expression of the water-channel protein aquaporin 4 in the H-Tx rat: possible compensatory role in spontaneously arrested hydrocephalus.

OBJECT: Aquaporin (AQP) water channels play an important role in water movement in the central nervous system. The authors used an animal model to examine the relationship between AQP4 expression and spontaneously arrested hydrocephalus. METHODS: . Congenitally hydrocephalic H-Tx (hH-Tx) rats and nonhydrocephalic H-Tx (nH-Tx) rats were used in the study. Brain tissue sections were obtained from animals in both groups at 1 day, 1 week, 4 weeks, and 8 weeks of age. Sections were immunostained using AQP4 antibodies, and AQP4 expression was assessed. In the nH-Tx group, no AQP4 expression was seen in 1-day-old rats, and AQP4 expression was found in astrocytes around capillaries of the cerebral cortex and in ependymal cells lining the ventricles in 1-week-old rats. In the 4- and 8-week-old nH-Tx animals, AQP4 expression was seen in subpial zones of the cortex, on foot processes of pericapillary astrocytes, and in periventricular regions. A marked increase in cerebral cortical expression of AQP4 was observed at 8 weeks in the hH-Tx rats but not in the nH-Tx rats. CONCLUSIONS: The authors hypothesize that the differences in cerebral AQP4 expression in the 1-day-old and 1-week-old nH-Tx rats compared with the 4- and 8-week-old nH-Tx rats may be related to the fact that the cerebrospinal fluid (CSF) circulation of newborns and infants differs from that of adults. It is also possible that the increased expression of AQP4 seen in the 8-week-old hH-Tx animals was related to the development of alternative pathways of CSF circulation, which also may occur in instances of spontaneously arrested hydrocephalus.

Age Factors↗

Analysis of cerebellum proteomics in the hydrocephalic H-Tx rat.

The H-Tx rat is a polygenic inherited model of hydrocephalus. In order to identify disease-specific biomarkers associated with congenital hydrocephalus, comparative proteomic analysis was used to screen cerebellum proteins in H-Tx rats at 1 day after birth. Seven proteins showed significant changes in hydrocephalic H-Tx rats compared with Sprague-Dawley and normal H-Tx rats, including HMG-1, CDCrel-1A, mitochondrial ATP synthase, ERp29, NADP+-ICDH, CCT beta and gamma. This indicates that the hydro-cephalus in H-Tx rats may be the result of a panel of proteins. In particular, the presence of HMG-1 and lack of CDCrel-1 in hydrocephalic H-Tx rats suggests that the use of two protein markers will provide further insight with respect to congenital hydrocephalus.

Animals↗

[A case of intracranial dural arteriovenous fistula presenting with brainstem infarction].

A 68-year-old female presented with the disturbance of brainstem function. Brain T2 weighted and FLAIR (fluid-attenuated inversion recovery) magnetic resonance imaging revealed the hyperintensity signal of the medulla oblongata, which led to diagnosis of brainstem infarction. Diagnostic cerebral angiography showed the dural arteriovenous fistula (DAVF) developed on the left transverse sinus (TS). Venous drainage route was consisted of retrograde leptomeningieal venous reflux of the cerebrum and spinal perimedullary vein via superior petrosal sinus. Venous hypertension of the brainstem was relieved by transvenous platinum coil selective embolization of superior petrosal sinus. The correct analysis of venous drainage pattern is essential for the curative endovascular surgery.

Aged↗

[Adams-Stokes attack due to complete atrioventricular block in a patient with acute promyelocytic leukemia during remission induction therapy using all-trans retinoic acid].

We describe a case of Adams-Stokes syncope due to complete atrioventricular block which occurred in a leukemic patient receiving all-trans retinoic acid (ATRA). Remission induction therapy was performed for a 46-year-old Japanese man with acute promyelocytic leukemia using ATRA (45 mg/m2), enocitabine (170 mg/m2, 5 days), and mitoxantrone (4 mg/m2, 3 days). On the 25th day of chemotherapy, syncope suddenly occurred. Electrocardiography revealed a complete atrioventricular block, and a temporary pacemaker was inserted on the following day. The block was persistent and the cardiac rhythm was dependent on the pacemaker. ATRA was discontinued on the 29th day because the arrhythmia was believed to be an adverse reaction to the ATRA regimen. The normal sinus rhythm was restored 15 days thereafter, and the patient eventually reached remission. He subsequently received 4 courses of consolidation therapy without any cardiovascular complications. Although ATRA sometimes induces arrhythmias, to the best of our knowledge this is the first report in the literature of such a critical ATRA-related arrhythmia.

Antineoplastic Combined Chemotherapy Protocols↗

Analysis of TGF-beta2 and TGF-beta3 expression in the hydrocephalic H-Tx rat brain.

INTRODUCTION: Transforming growth factor-beta (TGF-beta) is an important cytokine with modulatory actions in the nervous system. The development of hydrocephalus in mouse models resulting from the overexpression of TGF-beta1 has previously been described, but the mechanism by which this occurs remains obscure. METHODS: In order to evaluate the role of TGF-beta in hydrocephalus, we used SYBR Green I-based real-time quantitative RT-PCR method and Western blot analysis to analyze the TGF-beta2 and TGF-beta3 mRNA and protein expressions in the cerebral cortex of the H-Tx rat, a model of congenital hydrocephalus. RESULTS: The hydrocephalic H-Tx rat expressed significantly higher TGF-beta3 levels than their normal siblings (p<0.01) at 7 and 14 days of age. This difference became insignificant when analyzed at 21 days of age. On the other hand, such a difference has not been observed in the TGF-beta2 levels in the hydrocephalic H-Tx rat. CONCLUSIONS: These results suggest that TGF-beta2 and TGF-beta3 expression may be modulated differently in the hydrocephalus, and TGF-beta3 may contribute to the development of hydrocephalus in this rat model.

Age Factors↗

Effect of C-type natriuretic peptide (CNP) on water channel aquaporin-4 (AQP4) expression in cultured astrocytes.

Astrocytes play a vital role in volume and ion control in the central nervous system. C-type natriuretic peptide (CNP) may be involved in neuronal-glial signaling, but its physiological role has not yet been characterized. In our study, we found that CNP can regulate the water channel aquaporin-4 (AQP4) expression in cultured astrocytes. Using immunocytochemistry and enzyme immunoassay, we found that primary neuronal cultures exhibited a high level of reactivity to CNP, and that cultured astrocytes exhibited reactivity to cyclic GMP after exposure of CNP. Using RT-PCR, immunoblot and immunocytochemistry, we detected increased levels of AQP4 mRNA and AQP4 immunoreactivity in the cultured astrocytes after they had been exposed to CNP or cyclic GMP. These results suggest that CNP, which is mainly produced by the neurons, effects the level of AQP4 in the astrocytes. Therefore, CNP may be a regulator of water homeostasis in the central nervous system.

Animals↗

Apoptosis of gastric cancer cell line MKN45 by photodynamic treatment with photofrin.

The aim of this study was to investigate the mechanism of cell death by photodynamic therapy (PDT) in the gastric cancer cell line MKN45 with focus on the mechanism of apoptosis. Gastric cancer cells (MKN45) were incubated with Photofrin for up to 24 h before exposure to He-Cd laser (441 nm, 1 J/cm2). Cell viability was assessed by the methyl-tetra-zolium assay after exposure to light. A 95% cell death (LD95) was measured with 10 microg/ml of Photofrin. DNA ladder formation and chromatin condensation were seen within 60 min. Caspase-3-like and caspase-9-like activities increased from 15 min after exposure to light. Reduction of rhodamine 123 uptake started at 30 min. Caspase-inhibitor VAD-fmk (10 mM) inhibited apoptosis, but did not influence cell viability. In conclusion, Photofrin-mediated PDT in the gastric cancer cell line MKN45 induces apoptosis within 60 min, and mitochondrial damage is likely as the first event of apoptosis.

Antineoplastic Agents↗

Treatment of unilateral lambdoid synostosis with cranial distraction.

The accurate diagnosis and treatment of posterior plagiocephaly have been a source of controversy. The unilateral lambdoid synostosis that is characterized by flattening of ipsilateral occipital bone is a rare type of craniosynostosis. An 8-month-old infant with unilateral lambdoid synostosis is reported. The patient exhibited right occipital flattening, mastoid bulge, and right frontal bone prominence, with the right auricle displaced anteroinferiorly on gross examination. A Towne projection radiograph of the skull and three-dimensional computed tomography scans revealed that the right lambdoid suture was prematurely fused. Correction of the cranial shape was performed using distraction osteogenesis combined with a barrel stave osteotomy. Significant improvement in the skull was observed 1 year after surgery.

Cranial Sutures↗

Sensitization of human glioblastomas to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by NF-kappaB inhibitors.

Glioblastoma is the most malignant form of primary brain tumor in adults, with no effective therapy and a low survival rate. TRAIL is a member of the TNF family, which selectively induces apoptosis in certain neoplastic cells, but not normal cells. In this study, we investigated the sensitivity of 7 human glioblastoma cell lines to TRAIL and the expression in them of TRAIL receptors. TRAIL exhibited significant cytotoxicity in 5 of 7 glioma cell lines. These glioblastoma cell lines expressed TRAIL-R2, but not TRAIL-R1, R3, or R4. However, no correlation was observed between the TRAIL sensitivity and the TRAIL-R2 expression level, suggesting that there is an additional determinant of TRAIL sensitivity. Treatments with NF-kappaB inhibitors, such as LLnL, MG132, and SN50, significantly increased the sensitivity of glioma cells to TRAIL. These results suggested that activation of NF-kappaB is a protective mechanism against TRAIL-induced cell death in some glioma cells, and thus NF-kappaB inhibitors may be useful to improve the clinical treatment of glioblastoma with TRAIL.

Apoptosis Regulatory Proteins↗

Correlation of EPHA2 overexpression with high microvessel count in human primary colorectal cancer.

Evidence suggests that the erythropoietin-producing hepatocellular (EPH) receptor tyrosine kinases (RTKs) and their ephrin (EFN) ligands are involved in human carcinogenesis. Expression of two of them, EFNA1 ligand and its receptor, EPHA2, has been proposed to contribute to tumor-induced neovascularization. Colorectal cancers were examined for expressions of EPHA2 and its ligand EFNA1 by semi-quantitative RT-PCR, and double-immunostained for EPHA2 and CD34. Microvessels in the tumors were counted. Double-staining was also performed in 25 cases of adenoma with focal cancer for comparison. Trends of overexpression of both EPHA2 and EFNA1 was found in tumor tissue compared to the corresponding normal tissue in the same specimen [22/37 (59.5%) and 25/37 (67.5%), respectively; P = 0.100 for EPHA2 and P = 0.009 for EFNA1]. Overexpression of EPHA2 and EFNA1 was noted more frequently in the early stage than in the late stage [EPHA2, 15/21 (71.4%) vs. 7/16 (43.8%), P = 0.007; EFNA1, 15/21 (71.4%) vs. 10/16 (62.5%), P = 0.007]. Both EPHA2 and EFNA1 were more frequently overexpressed in smaller tumors (less than 5 cm) than in larger tumors [EPHA2, 15/21 (71.4%) vs. 7/16 (43.8%), P = 0.017; EFNA1, 16/21 (76.2%) vs. 8/16 (50%), P = 0.001]. Tumors less than 5 cm in diameter and in stages I and II were significantly more likely to overexpress EPHA2 and EFNA1 (P = 0.001 for EPHA2, P = 0.001 for EFNA1). Microvessel counts (MVCs) after immunostaining for CD34 were significantly correlated (r = 0.343, P = 0.037) with overexpression of EPHA2. EPHA2-expressing focal cancer also surrounded microvessels in adenomas with focal cancers. These findings suggest an involvement of EPHA2 in colon carcinogenesis, mainly in stages I and II, and probably through their effect on microvessel induction.

Aged↗

Reduced intensity allogeneic stem cell transplantation for systemic primary amyloidosis refractory to high-dose melphalan.

Complete elimination of the plasma cell dyscrasia is a rational therapeutic goal, as intercepting supply of precursor protein is a necessary condition for a major regression of amyloid deposits. High-dose melphalan with autologous stem cell transplantation has shown the ability to induce complete hematological response (HR) along with recovery of organ dysfunction. However, the rate of HR with this treatment rarely exceeds 40%. We describe here the first known case of successful reduced intensity allogeneic stem cell transplantation (RIST) for a patient with primary amyloidosis complicated with nephrotic syndrome but without cardiac disease, who had obtained only partial HR by high-dose melphalan with autologous stem cell transplantation. RIST may be feasible and be capable of achieving complete HR along with recovery from nephrotic syndrome with acceptable toxicity.

Amyloidosis↗

Microarray analysis of temporal gene responses to ionizing radiation in two glioblastoma cell lines: up-regulation of DNA repair genes.

To determine the patterns of gene expression responsible for the radiosensitivity of glioblastoma cells, we analyzed transcriptional changes after ionizing radiation in different cell lines. After completing clonogenic survival assays, we selected two glioblastoma cell lines with different radiosensitivities. Subsequently, they were investigated by using the technique of DNA microarray, and we then categorized the upregulated genes into 10 groups. Between the two cell lines, the difference in the percentage of DNA repair/replication category was the largest, and this category was present at a greater percentage with radioresistant cell line U87MG. Moreover, among the commonly upregulated genes, the DNA repair/replication category was present in the largest percentage. These genes included G22P1 (Ku70) and XRCC5 (Ku80) genes known as important members of the nonhomologous end-joining (NHEJ) pathway of DNA double strand break (DSB) repair. Furthermore, cell line that specifically upregulated genes included the members of major pathways of DNA DSB or single strand damage repair. These pathways were not only NHEJ, but also homologous recombination (HR) and postreplication repair (PRR). In conclusion, the distribution of genes involved in the DNA repair/replication category was most different between two human glioblastoma cell lines of different radiosensitivities. Among commonly upregulated genes, the DNA repair/replication category was present in the largest percentage.

Adaptation, Physiological↗

Spontaneous carotid-cavernous fistula in a patient with Ehlers-Danlos syndrome type IV--case report.

A 30-year-old female complained of sudden onset of severe proptosis, chemosis, diplopia, and bruit. Right carotid angiography showed a high-flow direct carotid-cavernous fistula (CCF) draining into the engorged superior ophthalmic vein, inferior petrosal sinus, and pterygoid plexus. The patient experienced retroperitoneal bleeding from a ruptured right renal artery after undergoing cerebral angiography. We suspected Ehlers-Danlos syndrome (EDS) type IV, which was confirmed by showing cultured fibroblasts failed to secrete procollagen type III. Endovascular surgery cannot be considered the treatment method of choice in view of the fragility of the arteries and veins in patients with EDS type IV. We treated our patient with extracranial internal carotid artery ligation. Currently, there is no ideal treatment for CCF in patients with EDS type IV. Since CCF is rarely life-threatening, the investigative approach and course of treatment must consider the associated vascular fragility.

Adult↗