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Biomedical subjects

N Arai

Publications and source records attributed to N Arai.

At least 109 records · Page 6Linked to original sources
PubMed1997

Cytokine signal networks and a new era in biomedical research.

Elucidation of the biochemical nature of the signal transduction pathway that regulate transcription and replication is the focus of attention in molecular biology. This research may make feasible manipulation of growth and differentiation of mammalian cells, which in turn would have profound implication in biomedical research on cell and gene therapy, and development of pharmaceutical products. Cytokines control growth, differentiation, death, and function of cells of lymphocytic, hemopoietic systems, and together with nerve cells provide a pertinent model to study intercellular communications and intercellular signal networks. This review outlines general features of signal transduction and several aspects of cytokine networks are discussed with emphasis on: transcriptional regulation of Th1 and Th2-specific cytokine genes in T cells, the roles of cytokines and their receptors in growth and differentiation of hemopoietic cells, and the manipulation of cytokine networks.

Animals↗
PubMed1997

Neuropathology of the dentate nucleus in developmental disorders.

The dentate nucleus was examined histologically and immunohistochemically in 47 cases of nonprogressive developmental disorders. Neuronal loss and/or atrophy was observed in 13 cases, while mild neuronal lesions, characterized by dendritic swelling and/or the appearance of eosinophilic materials around the neurons, were exhibited in 20 cases. The former change was accompanied by diffuse central nervous system involvement, and the etiology was perinatal hypoxic ischemic encephalopathy, acute encephalopathy, and meningoencephalitis in most cases. On the other hand, most of the patients with kernicterus showed the latter change. Immunohistochemically, the mild neuronal lesions mimicking grumose, degeneration, described in some neurodegenerative diseases, seemed to reflect the changes of Purkinje cell terminals. It is suggested that secondary structural alteration of the dentate neurons in the absence of severe atrophy can occur in nonprogressive developmental disorders.

Adolescent↗
PubMed1997

Surgical treatment of epilepsy from schizencephaly with fused lips.

BACKGROUND: Surgical treatment of schizencephaly with fused lips has been reported in few cases. In all of the previously reported cases, temporal lobectomy was selected as a major surgical treatment, except for one case with cortical resection. We present a case of direct resection of dysplastic walls of the schizencephalic cleft and the surrounding epileptic area. CASE: This 20-year-old college student with medication-resistant epilepsy was surgically treated by subpial cortical resection of the epileptogenic area around a schizencephalic cleft. Magnetic resonance imaging showed an unilateral schizencephalic cleft with fused lips in the right parietal lobe. Pathologic examination demonstrated dysplastic neurons in the epileptogenic cortex. Intraoperative electrocorticography clearly detected epileptiform discharges around the cleft, and the epileptogenic lesion was completely resected. He has been seizure-free for 1 year since the operation and he has no neurologic deficits. CONCLUSION: Subpial resection of the dysplastic cortex surrounding the cleft under the guide of electrocorticography is an effective and minimally invasive procedure for the treatment of schizencephaly.

Adult↗
PubMed1997

Apolipoprotein E in progressive supranuclear palsy in Japan.

Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease which shows several psychiatric and neurologic symptoms: pseudobulbar palsy, supranuclear ocular palsy, extrapyramidal rigidity, gait ataxia, and dementia. Almost all cases seem to be sporadic; therefore, the elucidation of risk factors is important to clarify the pathological mechanism. Apolipoprotein E4 (ApoE4) is now well established as a risk factor of Alzheimer's disease (AD). Here we report the ApoE allele frequency in PSP, which shares pathological findings such as neurofibrillary tangle (NFT) with AD. NFT is an important sign for the derangement of normal cytoskeletons in degenerating neurons. Although there was no significant increase in epsilon 4 allele frequency in the present series of PSP cases compared with that in the Japanese controls, there was a significant increase in the epsilon 2 allele frequency in PSP compared to controls.

Aged↗
PubMed1997

Calcineurin-dependent nuclear translocation of a murine transcription factor NFATx: molecular cloning and functional characterization.

Members of the nuclear factor of activated T cells (NFAT) are involved in the induction of a number of cytokine genes. We report here cDNA cloning and chromosomal localization of a murine homologue of human NFATx, designated as mNFATx1, and its splicing variants mNFATx2 and m delta NFATx. Northern blot analysis showed mNFATx1 to be predominantly expressed in the thymus. mNFATx1, but not m delta NFATx, produced in COS-7 cells, bound to all NFAT-binding sites of the interleukin (IL)-2 and IL-4 promoters tested. Immunofluorescence assay showed that both mNFATx1 and m delta NFATx introduced into COS-7 cells localized predominantly to the cytoplasm, but did translocate to the nucleus, either by cotransfection with an active form of calcineurin or wild-type calcineurin followed by stimulation with calcium ionophore. Translocation of mNFATx1 correlated well with activation of the murine IL-2 promoter; mNFATx1 translocated under conditions described above, in combination with phorbol 12-myristate 13-acetate, activated the transiently transfected murine IL-2 promoter. Thus, nuclear-translocated mNFATx1 is involved in activation of the IL-2 promoter. These results provide the first evidence for the requirement of calcineurin in the control of mNFATx imported from the cytoplasm to the nucleus and implies that mNFATx may possibly be a substrate of calcineurin in vivo.

Amino Acid Sequence↗
PubMed1997

Four P-like elements are required for optimal transcription of the mouse IL-4 gene: involvement of a distinct set of nuclear factor of activated T cells and activator protein-1 family proteins.

We previously identified the P sequence as a critical regulatory element of the human IL-4 promoter. In the mouse IL-4 promoter, there are five elements homologous to the human P sequence designated conserved lymphokine element 0 (CLE0), P, P2, P3 and P4. To characterize the role of these P-like elements and their binding factors in the native promoter, we did transient transfection and electrophoretic mobility shift assays (EMSA). Transfection of EL-4 cells with the IL-4 promoter-reporter constructs carrying mutated P-like elements showed that four P-like elements, CLE0, P, P2 and P4, but not P3, were required for optimal activation of the IL-4 promoter. EMSA showed that both constitutive and inducible complexes bound to CLE0, P, P2 and P4, whereas only a constitutive complex bound to P3. In competition and antibody supershift assays in EMSA, complexes formed with P or P2 proved to contain nuclear factor of activated T cells (NFAT) family proteins as major components. Activator protein (AP)-1 family proteins interacted with CLE0, P, P2 and P4. NFAT/AP-1 complex formed only with P and P2. Cross-competition assays among the P-like elements revealed element-specific and common complexes. Six tandem repeats of the P element linked to the SV40 promoter responded to phorbol 12-myristate 13-acetate, while that of other elements did not. It would thus appear that components of each P-like element-binding complexes are not identical and may coordinately contribute to transcriptional activity.

Animals↗
PubMed1997

Control of NFATx1 nuclear translocation by a calcineurin-regulated inhibitory domain.

The nuclear factor of activated T cells (NFAT) regulates cytokine gene expression in T cells through cis-acting elements located in the promoters of several cytokine genes. NFATx1, which is preferentially expressed in the thymus and peripheral blood leukocytes, is one of four members of the NFAT family of transcription factors. We have performed domain analysis of NFATx1 by examining the effects of deletion mutations. We found that NFATx1 DNA binding activity and interaction with AP-1 polypeptides were dependent on its central Rel similarity region and that transcriptional activation was reduced by deletions of either its N-terminal domain or its C-terminal domain, suggesting the presence of intrinsic transcriptional activation motifs in both regions. We also identified a potent inhibitory sequence within its N-terminal domain. We show that the inactivation of the inhibition was dependent on the activity of calcineurin, a calcium-calmodulin-dependent phosphatase. We also show that calcineurin associated with the N-terminal domain of NFATx1 at multiple docking sites and caused a reduction of size, indicative of dephosphorylation, in NFATx1. We have mapped the inhibitory activity to less than 60 residues, containing motifs that are conserved in all NFAT proteins. Finally, we demonstrate that deletion in NFATx1 of the mapped 60 residues leads to its nuclear translocation independent of calcium signaling. Our results support the model proposing that the N-terminal domain confers calcium-signaling dependence on NFATx1 transactivation activity by regulating its intracellular localization through a protein module that associates with calcineurin and is a target of its phosphatase activity.

Amino Acid Sequence↗
PubMed1997

Focal cortical dysplasia: appearance on MR images.

PURPOSE: To clarify the magnetic resonance (MR) imaging characteristics of focal cortical dysplasia (FCD). MATERIALS AND METHODS: The authors reviewed the MR images of 14 patients with FCD, which was confirmed with histologic examination. RESULTS: MR images exhibited FCD in 13 of the 14 patients. All lesions were localized to part of one hemisphere. T2-weighted images showed blurring of the gray matter-white matter junction and abnormal signal intensity in the white matter in 11 patients. T1-weighted images showed blurring of the gray matter-white matter junction in seven patients, broad gyri in nine, thick cortices in nine, abnormal sulci in 10, and focal enlargement of the overlying subarachnoid space or adjacent ventricle in eight. Surgical specimens exhibited disruption of cortical lamination without abnormal gyration in all patients, cytomegalic neurons in the cortex in three, disorganized bizarre glial cells in the cortex in seven, ectopic neurons or bizarre glial cells in the white matter in nine, and blurring of the gray matter-white matter junction in one. CONCLUSION: Blurring of the gray matter-white matter junction with abnormal signal intensity in the white matter on T2-weighted images is characteristic of FCD. The presence of ectopic neurons and bizarre glial cells, dysmyelination, and a reduction in the number of myelinated fibers might have been responsible for the MR imaging characteristics.

Adolescent↗
PubMed1997

Coexistence of ganglioglioma and cortical dysplasia in a patient with intractable epilepsy--case report.

An 8-year-old girl presented with coexistence of ganglioglioma and cortical dysplasia manifesting as intractable epilepsy. Preoperative computed tomography demonstrated a small calcified lesion in the left frontal lobe which was not diagnosed as ganglioglioma. Magnetic resonance imaging also failed to demonstrate positive evidence of ganglioglioma or cortical dysplasia. A calcified tumor and the surrounding epileptogenic areas were resected under electrocorticography (ECoG) guidance. Histological examination revealed coexistence of ganglioglioma and cortical dysplasia. The patient became seizure-free after surgery. Resection of the ganglioglioma together with the adjacent epileptogenic area under intraoperative ECoG guidance is important to achieve a successful surgical result in patients with ganglioglioma.

Brain Mapping↗
PubMed1997

Amphistin, a new melanogenesis inhibitor, produced by an actinomycete.

A new melanogenesis inhibitor, named amphistin, was isolated from the fermentation broth of an actinomycete strain KP-3052. Amphistin was purified from the culture filtrate by the combination of cation exchange, gel filtration, and aminosilyl silica gel chromatographic methods. The structure of amphistin was elucidated as gamma-(beta-histidinoalanino)homoalanine by NMR experiments including 1H-15N HMBC experiment and other spectroscopic analyses. Amphistin inhibited the melanogenesis of B16 melanoma cells at concentration of 6.8 microM.

Actinomycetaceae↗
PubMed1997

Expression of cyclooxygenase genes and involvement of endogenous prostaglandin during osteogenesis in the rat tibial bone marrow cavity.

Many researchers have demonstrated that the administration of prostaglandins (PGs), especially PGE2, increases the bone volume in vivo. It is still not clear how endogenous PG is associated with such bone formation. Cyclooxygenase (COX), which acts in the synthesis of PG from arachidonic acid, has been recently revealed to have two subtypes, a constitutive type (COX-1) and an inducible one (COX-2). We examined the expression of each COX subtype during osteogenesis with the established model of the rat tibial medullary cavity in which osteogenesis can be induced by the injection of colchicine. The expression of both COX-1 and COX-2 genes was enhanced after colchicine injection in the early stage before the start of bone formation. Only the COX-2 gene expression was elevated again later during the beginning of bone formation. Furthermore, the daily administration of indomethacin, COX inhibitor, could reduce the bone mass induced by colchicine in the rat tibiae. These data indicate that endogenous PGs are associated with osteogenesis in this model. Moreover, the present study suggests that COX-2 and COX-1 would both be involved in the early stage of osteogenesis, and COX-2 is likely to be more associated with the maturation of osteoblasts in the later stage.

Animals↗
PubMed1997

[Pathological spectrum of neuronal migration disorder].

A variety of brain malformative lesions, resulting mainly from abnormalities in neuronal migration, have been recently highlighted with increasing knowledge on surgical pathology of intractable epilepsy. In this article, a wide spectrum of pathology in and around the neuronal migration period are reviewed. Morphological changes of lissencephalies, polymicrogyria, microdysgenesis and focal cortical dysplasia were described, as well as some problems in the classification of malformative brains.

Brain↗
PubMed1997

[Proton MR spectroscopy of hyperplastic hematopoietic marrow in aplastic anemia].

The purpose of this study was to compare the findings of magnetic resonance (MR) spectroscopy of hyperplastic hematopoietic marrow with those of normal bone marrow. Twenty-four samples of normal marrow from eight control subjects and 19 samples of hyperplastic marrow in aplastic anemia were examined with a 1.5T MR unit. The former showed low intensity on opposed-phase T1-weighted images, while the latter showed high intensity on both fast STIR and opposed-phase T1-weighted images. MR spectroscopy quantitatively confirmed that the water: fat ratio was increased and the transverse relaxation time of water was changed in hyperplastic bone marrow, compared with normal bone marrow. In summary, MR imaging is able to detect hematopoietic regions among a wide range of bone marrow of aplastic anemia, while MR spectroscopy allowed us to quantitatively analyze the cell population of hyperplastic hematopoietic marrow in aplastic anemia.

Adolescent↗
PubMed1997

Low epithelial cell proliferation and absence of oncoprotein expression in juvenile polyposis of the stomach, with or without tumors.

OBJECTIVES: To assess cell proliferation and analyze oncogenetic abnormalities in cases of juvenile polyposis of the stomach (JPs), with or without coexisting tumors. METHODS: The Ki-67 labeling indices (KLI) were compared for juvenile polyps and coexisting tumors in three cases of JPs along with values for gastritis, foveolar epithelial hyperplastic polyps, adenomas, and carcinomas. Expression of p53, Bcl-2, and c-ErbB-2 in tumors was examined immunohistochemically, and a search for c-Ki-ras mutations was made by DNA direct sequencing. RESULTS: The KLI for JPs did not significantly differ between cases, being consistently lower than the values for both hyperplastic polyps and gastritis. The KLI for the papillary tumors and a signet ring cell carcinoma found in association with JPs tended to be lower than those for their conventional counterparts. P53, but not Bcl-2 and c-ErbB-2, was focally expressed in the papillary tumors, whereas all three were absent in the signet ring cell carcinoma, in the JPs. No c-Ki-ras mutations were detected in the papillary tumors. CONCLUSIONS: The cell proliferation of JPs is relatively low and the polyps can be considered hamartomatous. However, neoplastic change clearly can occur in association with a relative increase in proliferative activity being observed in coexisting tumors. Low cellular proliferative activity and absence of oncogenetic abnormalities in tumors of JPs, compared with their conventional counterpart tumors, suggest that pathways of tumorigenesis and genetic alteration in JPs may be different from those in their conventional counterparts.

Adenocarcinoma↗
PubMed1997

[A case of pulmonary arteriovenous fistula presenting as multiple brain abscesses after a sustained period without treatment].

A 64-year-old man was admitted to our hospital with multiple brain abscesses accompanied by pulmonary arteriovenous fistula (PAVF). He had been diagnosed with PAVF eight years previously, but had refused any treatment despite a developing exertional dyspnea. Rendu-Osler-Weber disease was diagnosed as well because the patient exhibited teleangiectasis of the nasopharyngeal mucosa and persistent gastro-intestinal bleeding. Despite administration of antibiotics and corticosteroids the abscesses perforated into the lateral ventricle. The natural history of this rare disease is still incompletely understood. Thus, the time at which treatment should be commenced remains unclear. However the natural course of PAVF is unsatisfactory, and it appears that treatment by surgery and/or embolization should be considered in all cases.

Arteriovenous Fistula↗