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Biomedical subjects

N Mori

Publications and source records attributed to N Mori.

At least 91 records · Page 5Linked to original sources

Induction of monocyte chemoattractant protein 1 by Helicobacter pylori involves NF-kappaB.

Helicobacter pylori stimulates secretion of monocyte chemoattractant protein 1 (MCP-1) from gastric epithelial cells. Secretion of this chemokine may be instrumental in monocyte infiltration of the gastric epithelium that characterizes H. pylori gastritis. The aim of this study was to identify the mechanism by which H. pylori induces MCP-1 production. Induction of MCP-1 mRNA was assessed by reverse transcription-PCR. We used luciferase reporter assays to monitor activation of the MCP-1 gene promoter and electrophoretic mobility shift assays to explore binding of transcription factors to this promoter. H. pylori infection increased MCP-1 mRNA expression from gastric epithelial cells. Induction of MCP-1 mRNA relies on an intact cag pathogenicity island. We identified two closely spaced NF-kappaB-binding sites within the MCP-1 distal enhancer as required for H. pylori-induced MCP-1 gene transcription. H. pylori infection led to the specific activation of NF-kappaB complexes containing p50 and p65. Kinase-deficient mutants of NF-kappaB-inducing kinase (NIK) and IkappaB kinases (IKK) caused suppression of MCP-1 distal enhancer-dependent reporter activity following H. pylori infection. H. pylori infection induces the activation of NF-kappaB via the NIK-IKK signaling complex, leading to MCP-1 gene transcription in gastric epithelial cells.

Chemokine CCL2↗

Immunological and PCR analyses for Borna disease virus in psychiatric patients and blood donors in Japan.

The involvement of Borna disease virus (BDV) in psychiatric diseases in humans remains controversial. T-cell memory response and seroprevalence of BDV in patients with psychiatric disorders and blood donors in Japan were evaluated collectively by Western blot (WB) analysis with inhibition test, electrochemiluminescence immunoassay, immunofluorescence assay, and T-cell proliferative response as well as detection of BDV p24 RNA in peripheral blood mononuclear cells (PBMCs). Positive proliferative responses to both BDV p40 and p24 proteins were detected in 9% of patients with mood disorders (4 of 45), 4% of schizophrenic patients (2 of 45), and 2% of blood donors (1 of 45). By WB analysis, the antibody to BDV p40 was detected only in 2% of patients with mood disorders (1 of 45). The BDV p24 antibody was detected in 2% of patients with mood disorders (1 of 45) and 9% of schizophrenic patients. (4 of 45) No plasma reacted with both BDV proteins. The finding of a lower seroprevalence than previously reported suggests the presence of false-positive cases in the previous report. BDV RNA was detected only in 2% of patients with mood disorders (1 of 45). In these three serological assays, T-cell responses, and PCR analysis, there was no significant difference in the prevalence among the three groups. However, we found three psychiatric patients who were positive for both BDV antibodies and T-cell proliferative responses and one patient who was positive for BDV RNA in PBMCs. These findings suggest the usefulness of the proliferative T-cell response and that certain individuals are infected with BDV or a BDV-related virus.

Adolescent↗

The neuron-restrictive silencer element-neuron-restrictive silencer factor system regulates basal and endothelin 1-inducible atrial natriuretic peptide gene expression in ventricular myocytes.

Induction of the atrial natriuretic peptide (ANP) gene is a common feature of ventricular hypertrophy. A number of cis-acting enhancer elements for several transcriptional activators have been shown to play central roles in the regulation of ANP gene expression, but much less is known about contributions made by transcriptional repressors. The neuron-restrictive silencer element (NRSE), also known as repressor element 1, mediates repression of neuronal gene expression in nonneuronal cells. We found that NRSE, which is located in the 3' untranslated region of the ANP gene, mediated repression of ANP promoter activity in ventricular myocytes and was also involved in the endothelin 1-induced increase in ANP gene transcription. The repression was conferred by a repressor protein, neuron-restrictive silencer factor (NRSF). NRSF associated with the transcriptional corepressor mSin3 and formed a complex with histone deacetylase (HDAC) in ventricular myocytes. Trichostatin A (TSA), a specific HDAC inhibitor, relieved NRSE-mediated repression of ANP promoter activity, and chromatin immunoprecipitation assays revealed the involvement of histone deacetylation in NRSE-mediated repression of ANP gene expression. Furthermore, in myocytes infected with recombinant adenovirus expressing a dominant-negative form of NRSF, the basal level of endogenous ANP gene expression was increased and a TSA-induced increase in ANP gene expression was apparently attenuated, compared with those in myocytes infected with control adenovirus. Our findings show that an NRSE-NRSF system plays a key role in the regulation of ANP gene expression by HDAC in ventricular myocytes and provide a new insight into the role of the NRSE-NRSF system outside the nervous system.

3' Untranslated Regions↗

Detection of minimal residual disease in a patient having acute myelogenous leukemia with t(16;21)(p11;q22) treated by allogeneic bone marrow transplantation.

A 29-year-old woman having acute myelogeneous leukemia-M1 subtype with the chromosomal abnormality t(16;21)(p11;q22) is presented. Complete blood count at onset showed a hemoglobin level of 7.2 g/dl, a platelet count of 48 x 10(9)/l, and a white blood cell count of 161.2 x 10(9)/l with 99% blasts and 1% lymphocytes. Bone marrow aspiration revealed massive proliferation of blasts that were positive for CD13, CD33, CD34, CD56 and myeloperoxidase, and negative for other T-cell, B-cell and monocytic markers. After achieving complete remission following conventional chemotherapy, she received an HLA-matched bone marrow transplantation (BMT) from her sibling after conditioning with busulfan, etoposide and cyclophosphamide. However, 9 months later, the leukemia relapsed as a painful extramedullary mass in her left femur. In spite of intensive re-induction chemotherapy, she died of progressive disease and sepsis. Although we could not detect the TLS/FUS-ERG fusion transcripts by reverse transcriptase-polymerase chain reaction in pre-BMT remission phase, they were clearly detectable in bone marrow cells obtained 6 months after transplantation with no translocation detected by conventional cytogenetics. We consider that even high-dose chemotherapy with BMT may not be effective in the eradication of this type of leukemia, and that the detection of minimal residual disease possibly contributes to the better planning of the therapeutic strategy.

Adult↗

Methamphetamine-related psychiatric symptoms and reduced brain dopamine transporters studied with PET.

OBJECTIVE: A positron emission tomography (PET) study has suggested that dopamine transporter density of the caudate/putamen is reduced in methamphetamine users. The authors measured nucleus accumbens and prefrontal cortex density, in addition to caudate/putamen density, in methamphetamine users and assessed the relation of these measures to the subjects' clinical characteristics. METHOD: PET and 2-beta-carbomethoxy-3beta-(4-[(11)C] fluorophenyl)tropane, a dopamine transporter ligand, were used to measure dopamine transporter density in 11 male methamphetamine users and nine male comparison subjects who did not use methamphetamine. Psychiatric symptoms in methamphetamine users were evaluated by using the Brief Psychiatric Rating Scale and applying a craving score. RESULTS: The dopamine transporter density in all three of the regions observed was significantly lower in the methamphetamine users than the comparison subjects. The severity of psychiatric symptoms was significantly correlated with the duration of methamphetamine use. The dopamine transporter reduction in the caudate/putamen and nucleus accumbens was significantly associated with the duration of methamphetamine use and closely related to the severity of persistent psychiatric symptoms. CONCLUSIONS: These findings suggest that longer use of methamphetamine may cause more severe psychiatric symptoms and greater reduction of dopamine transporter density in the brain. They also show that the dopamine transporter reduction may be long-lasting, even if methamphetamine use ceases. Further, persistent psychiatric symptoms in methamphetamine users, including psychotic symptoms, may be attributable to the reduction of dopamine transporter density.

Adult↗

Cell type-specific localization of sphingosine kinase 1a in human tissues.

Cell type-specific localization of sphingosine kinase 1a (SPHK1a) in tissues was analyzed with a rabbit polyclonal antibody against the 16 C-terminal amino acids derived from the recently reported mouse cDNA sequence of SPHK1a. This antibody (anti-SPHK1a antibody) can react specifically with SPHK1a of mouse, rat, and human tissues. Utilizing its crossreactivity to human SPHK1a, the cell-specific localization of SPHK1a in human tissues was histochemically examined. Strong positive staining for SPHK1a was observed in the white matter in the cerebrum and cerebellum, the red nucleus and cerebral peduncle in the midbrain, the uriniferous tubules in the kidney, the endothelial cells in vessels of various organs, and in megakaryocytes and platelets. The lining cells of sinusoids in the liver and splenic cords in the spleen showed moderate staining. Columnar epithelia in the intestine and Leydig's cells in the testis showed weak staining patterns. In addition, TPA-treated HEL cells, a human leukemia cell line, showed a megakaryocytic phenotype accompanied with increases in immunostaining of both SPHK1a and SPHK enzyme activity, suggesting that SPHK1a may be a novel marker of megakaryocytic differentiation and that this antibody is also useful for in vitro study of differentiation models.(J Histochem Cytochem 49:845-855, 2001)

Animals↗

Single nucleotide polymorphisms in an STS region linked to the Ncc-tmp1A locus are informative for characterizing the differentiation of chromosome 1A in wheat.

Homoeoalleles of Ncc confer nucleus-cytoplasm (NC) compatibility on NC hybrids of wheat with the D plasmon of Aegilops squarrosa. To dissect the chromosomal region containing Ncc, a RAPD marker linked to the Ncc-tmplA locus, which is located on chromosome 1A of T timopheevi, was sequenced and converted to a PCR-based sequence-tagged-site (STS) marker. Five single nucleotide polymorphisms (SNPs) between T timopheevi and T turgidum. were detected in a 509-bp genomic DNA fragment. Based on the SNPs, the STS alleles in 164 accessions from emmer wheat, timopheevi wheat and two einkorn wheats, T. urartu and T. boeoticum were surveyed by PCR-RFLP analysis. The sequence comparisons and PCR-RFLP analyses revealed nine alleles based on six SNPs. These SNPs were highly conserved within each group of wheat, and all groups could be distinguished by particular combinations of the SNPs. All accessions of T. urartu had one unique STS allele as compared with the others. Our results indicate that the SNPs in the STS marker linked to the Ncc-tmplA locus would be informative for studies of the differentiation of chromosome 1A in wheat.

Alleles↗

(4E)-dehydrocitrals [(2E,4E)- and (2Z,4E )-3,7-dimethyl-2,4,6-octatrienals] from acarid mite Histiogaster sp. A096 (Acari: Acaridae).

A mixture of two monoterpenes was obtained as the opisthonotal gland secretion from unidentified Histiogaster sp. A096 (Acari: Acaridae), and their structures were elucidated to be (4E)-dehydrocitrals [(2E,4E)- and (2Z,4E)-3,7-dimethyl-2,4,6-octatrienals] by GC/MS, GC/FT-IR, UV and 1H-NMR spectra. Both isomers of (4E)-dehydrocitral prepared by syntheses in 4 steps from 3-methyl-2-butenal with 34.2% yields (based on the ylide) were separated by column chromatography into the (2E,4E)- and (2Z,4E)-3,7-dimethyl-2,4,6-octatrienal. Mass spectra together with GC retention times of the purified natural (4E)-dehydrocitrals were identical with those of synthetic (2E,4E)-3,7-dimethyl-2,4,6-octatrienal and (2Z,4E)-3,7-dimethyl-2,4,6-octatrienal. The geometry at the 2-C position of both synthetic (4E)-dehydrocitrals was confirmed by NOESY analyses. This is the first identification of (4E)-dehydrocitrals from the animal kingdom.

Acari↗

Phenotypes associated with replacement of His by Arg in the Pendred syndrome gene.

BACKGROUND: Pendred syndrome is often associated with inner ear malformations, especially enlarged vestibular aqueduct (EVA). Recently, mutations in the Pendred syndrome gene (PDS) have been reported in patients with EVA, in addition to those with classical Pendred syndrome. OBJECTIVE: The aim of this study was to investigate the genotype-phenotype correlations of PDS. METHODS: Each of the 21 exons and flanking splice regions of PDS was analysed by direct DNA sequencing in nine patients with EVA; allele-specific amplification was performed to confirm the mutation. Genetic analyses were compared with thyroid function tests, perchlorate discharge tests, thyroid volume and pure-tone audiogram. Magnetic resonance imaging was used to determine the volume of the endolymphatic duct and sac of each patient. RESULTS: A missense mutation, H723R, was identified in the homozygous state in three patients and in the heterozygous state in another three. Although none of the patients had goitre, increased serum thyroglobulin and an abnormal degree of iodide release were correlated with the number of mutant alleles identified. However, there was no relationship between the degree of hearing loss and the number of mutant alleles. CONCLUSION: The present study reveals that the number of mutant alleles correlates with the degree of subclinical thyroid abnormality, but not with the degree of hearing loss in Japanese patients with the PDS missense mutation H723R.

Adolescent↗

Differential vulnerability of inner and outer hair cell systems to chronic mild hypoxia and glutamate ototoxicity: insights into the cause of auditory neuropathy.

OBJECTIVE: To describe the effects of long-term mild hypoxia and of glutamate poisoning on the functional properties of the cochlea. METHODS: Outer hair cell activity was monitored using otoacoustic emissions and cochlear microphonics, and inner hair cell/cochlear afferent function was measured using neural responses (cochlear action potentials or auditory brainstem responses [ABRs]). RESULTS: In contrast to the effects of acute anoxia, in which all aspects of cochlear function are simultaneously lost, mild, long-term hypoxia results in a clear differential effect on outer versus inner hair cell systems. During a 2-hour period of mild hypoxia, ABR amplitude and threshold deteriorate significantly, whereas outer hair cell function, as reflected by otoacoustic emissions, shows little or no change. A similar dissociation between inner and outer hair cell function is observed during instillation of glutamate (1-10 mM), where the cochlear microphonic and the otoacoustic emissions are unchanged, whereas cochlear action potential amplitudes are reduced. CONCLUSION: These studies demonstrate a difference in vulnerability of inner and outer hair cell systems. The inner hair cell/cochlear afferent system is vulnerable to long-term, mild hypoxia; this may be an etiologic factor in hearing loss of cochlear origin, particularly in high-risk birth infants with auditory neuropathy.

Animals↗

Vascular endothelial growth factor and cellular chemotaxis: a possible autocrine pathway in adult T-cell leukemia cell invasion.

Our previous report (T. Hayashibara et al., Leukemia, 13: 1634-1635, 1999) revealed a possible link between high plasma vascular endothelial growth factor (VEGF) concentration and leukemic cell invasion in adult T-cell leukemia (ATL). However, the biological mechanism of this link has not been elucidated. The purpose of this study was to address that mechanism. Our present observations showed that VEGF mRNA was expressed in ATL cell lines. The corresponding protein was secreted into the extracellular environment, which suggested that the major source of plasma VEGF is ATL cells themselves. More interestingly, all of the cell lines examined were found to express the mRNA and protein for fms-like tyrosine kinase-1 (Flt-1), which is one of the receptors for VEGF. Cytofluorometric analysis demonstrated the VEGF binding potency of these cells. In clinical specimens, expression of VEGF and Flt-1 mRNAs was detected in all (100%) of 11 and 8 (73%) of 11 ATL patients, respectively. Cytofluorometric analysis revealed that VEGF effectively bound only to Flt-1-expressing cells. These findings are highly suggestive of an autocrine pathway involving VEGF operating in ATL. The proliferation of ATL cell lines was not affected by treatment with an anti-VEGF antibody or exogenous VEGF, which indicated that VEGF has no mitogenic effect on ATL cells. In contrast, we made the interesting finding that treatment with exogenous VEGF enhanced the chemotactic activities of some ATL cell lines, which may play a key role in ATL cell invasion. Collectively, these data lead us to propose a possible autocrine mechanism involving VEGF operating by way of Flt-1, in which ATL cells up-regulate their own chemotaxis to facilitate their invasion into various organs.

Adult↗

Aggregation pheromone activity of the female sex pheromone, beta-acaridial, in Caloglyphus polyphyllae (Acari: Acaridae).

Caloglyphus (= Sancasania) polyphyllae discharges from a pair of opisthonotal glands a characteristic set of volatiles, i.e. three monoterpenes and seven hydrocarbons. Among them, beta-acaridial, which is known as the female sex pheromone of the species and has antifungal activity, was newly identified as the aggregation pheromone for unfeeding and unmating mites. Feeding mites, however, exhibited sexually aroused behavior instead of the tendency to cluster when exposed to beta-acaridial. This is the first example of the compound demonstrating two pheromone functions depending upon the circumstances faced by the mites.

Acari↗