Biomedical subjects

Jun-ichi Satoh

Publications and source records attributed to Jun-ichi Satoh.

5 recordsLinked to original sources

PubMed2003

Detection of the 14-3-3 protein in the cerebrospinal fluid of Japanese multiple sclerosis patients presenting with severe myelitis.

Recent studies showed that the 14-3-3 protein is detectable in the cerebrospinal fluid (CSF) of prion-unrelated neurological diseases, such as meningoencephalitis and myelitis. To investigate the possible association between the amounts of the 14-3-3 protein in the CSF and the clinical severity of multiple sclerosis (MS), its levels were determined by Western blot in the CSF of the patients with relapsing-remitting MS (RRMS) (n=10), secondary progressive MS (SPMS) (n=7), primary progressive MS (PPMS) (n=2), and non-MS inflammatory diseases of the CNS (n=5). The 14-3-3 protein was identified in seven CSF samples, including four patients with SPMS in acute relapse, one with SPMS in remission accompanied by fresh cerebral infarction, one with RRMS in acute relapse, and one with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy. The patients positive for the CSF 14-3-3 protein immunoreactivity showed more severe disability and higher levels of pleocytosis, protein, IgG, beta2-microglobulin, and neuron-specific enolase in the CSF, compared with those negative for its immunoreactivity. Four of these patients exhibited extensive lesions distributed along multiple vertebral segments in the spinal cord on MRI. In contrast, none of the MS patients without an extensive involvement of the spinal cord showed the CSF 14-3-3 protein immunoreactivity. These results suggest that detection of the 14-3-3 protein in the CSF provides a marker for severe inflammation-induced extensive damage of the central nervous system tissues responsible for poor therapeutic responses and irreversible neurological deficits in MS.

14-3-3 Proteins↗

PubMed2003

Interferon therapy-responsive brain metabolic abnormalities in a case of adult-onset subacute sclerosing panencephalitis evaluated by 1H MRS analysis.

We describe a 22-year-old woman with an adult-onset, slowly progressive form of subacute sclerosing panencephalitis (SSPE), who was repeatedly evaluated by brain magnetic resonance spectroscopy (MRS). The brain lesion spectrum showed a decrease in N-acetylaspartate (NAA) resonance, an increase in inositol (Ins) resonance, and an unaltered choline signal. These findings suggest neuronal loss and reactive gliosis without inflammation, consistent with brain biopsy findings showing astrocytic proliferation unaccompanied by lymphocytic infiltrates. The unusually protracted clinical course might be attributable to an absence of inflammatory infiltrates in the brain. Intraventricular interferon injection plus oral inosine pranobex treatment produced a substantial improvement in the MRS findings, suggesting the validity of monitoring MRS in SSPE.

Adult↗

PubMed2003

Microarray analysis identifies interferon beta-regulated genes in multiple sclerosis.

The molecular mechanisms for the interferon beta (IFNbeta) treatment of multiple sclerosis (MS) remain to be characterized. Using cDNA microarray technology, we have compared the gene expression profile of T and non-T cells derived from relapsing-remitting MS before and after treatment with IFNbeta-1b. IFNbeta treatment significantly altered expression of 21 genes out of 1263 at 3 and 6 months after treatment. These genes included nine with IFN-responsive promoter elements. Whereas there was no change in Th1 or Th2 marker genes, some of the changes were unexpected but coincided with the beneficial effect of IFNbeta in MS.

Adult↗

PubMed2002

Mg2+ transport in the kidney.

Magnesium is abundant in biological systems and an important divalent cation in the human body. Mg2+ helps mediate cellular energy metabolism, ribosomal and membrane integrity. Additionally Mg2+ modulates the activity of several membrane transport and signal transduction systems. Despite its importance however, little is known about the molecular mechanisms of Mg2+ transport and homeostasis in mammals. In mammals the amount of Mg2+ absorption is about the same as the amount of Mg2+ excretion in urine. Additionally, when total Mg2+ intake is deficient, the kidney is capable of reabsorbing all filtered Mg2+. This balance between intake and excretion indicates that the kidney plays a principal role in maintenance of total body Mg2+ homeostasis. Within the kidney, Mg2+ filtered by the glomerulus is handled in different ways along the nephron. About 10-20% of Mg2+ is reabsorbed by the proximal tubule. the bulk of Mg2+ (about 50-70%) is reabsorbed by the cortical thick ascending limb of the loop of Henle. In this region, Mg2+ moves across the epithelium through the paracellular pathway, driven by the positive lumenal transepithelial voltage. A recently cloned human gene, paracellin-1 was shown to encode a protein localized to the tight junctions of the cortical thick ascending limb and is thought to mediate Mg2+ transport via the paracellular space of this epithelium. The distal convoluted tubule reabsorbs the remaining 5-10% of filtered Mg2+. This segment seems to play an important role in determining final urinary excretion, since there is no evidence for significant Mg2+ absorption beyond the distal tubule. Although many renal Mg2+ transport activities have been characterized, no Mg2+ transporter cDNAs have been cloned from mammalian tissues. Recent research has certainly expanded our knowledge of Mg2+ transport in kidney; but details of the transport processes and the mechanisms by which they control Mg2+ excretion must await cloning of renal Mg2+ transporters and/or channels. Such information would provide new concepts in our understanding of renal Mg2+ handling.

Animals↗

PubMed2002

The constitutive and inducible expression of Nurr1, a key regulator of dopaminergic neuronal differentiation, in human neural and non-neural cell lines.

Nur-related factor 1 (Nurr1), nerve growth factor-induced gene B (NGFI-B) and neuron-derived orphan receptor-1 (NOR-1) constitute the orphan nuclear receptor subfamily of transcription factors. Previous studies showed that midbrain dopaminergic neuronal precursor cells failed to differentiate in Nurr1-deficient mice. To investigate a role of Nurr1 in human neuronal function, Nurr1 mRNA expression was studied in human neural cell lines by RT-PCR and northern blot analysis. Nurr1, NGFI-B and NOR-1 mRNA were coexpressed in all human neural and nonneural cell lines under the serum-containing culture condition, except for SK-N-SH neuroblastoma, in which Nurr1 mRNA was undetectable. The levels of Nurr1, NGFI-B and NOR-1 mRNA were elevated markedly in NTera2 teratocarcinoma-derived neurons (NTera2-N), a model of differentiated human neurons, following a 1.5 or 3 h-exposure to 1 mM dibutyryl cyclic AMP or 100 nm phorbol 12-myristate 13-acetate. NGFI-B mRNA levels were also elevated in NTera2-N cells by exposure to 100 ng/mL brain-derived neurotrophic factor (BDNF). To identify Nurr1-target genes, the mRNA expression of 27 genes potentially involved in dopaminergic neuronal differentiation and survival, including BDNF, glia-derived neurotrophic factor, their receptors, tyrosine hydroxylase and alpha-synuclein, were studied in HEK293 cells following overexpression of Nurr1. None of these genes examined, however, showed significant changes. These results indicate that Nurr1, NGFI-B and NOR-1 mRNA are expressed constitutively in various human neural and non-neural cell lines under the serum-containing culture condition, and their levels are up-regulated in human neurons by activation of protein kinase A or protein kinase C pathway, although putative coactivators expressed in dopaminergic neuronal precursor cells might be required for efficient transcriptional activation of Nurr1-target genes.

Blotting, Northern↗