Search PubMed⌕ Search

Biomedical subjects

N Mori

Publications and source records attributed to N Mori.

At least 163 records · Page 9Linked to original sources
PubMed2000

A susceptibility locus for radiation lymphomagenesis on mouse chromosome 16.

BALB/cHeA (BALB/c) mice are sensitive to radiation lymphomagenesis, while STS/A (STS) mice are resistant. We have selected a recombinant mouse, R1, with a STS-derived D16Mit165-D16Mit34 segment in the vicinity of the centromere of chromosome 16 among progeny from a (CcS-7/Dem x BALB/c)F1 x BALB/c backcross. To test the susceptibility to radiation lymphomagenesis, we generated a genetic cross by mating the male and female R1 progeny obtained by 4-6 backcrosses of R1 to BALB/c. The mice were subjected to 4 x 1.7 Gy of X-irradiation. Of 120 mice analyzed, 94 developed lymphomas (91, of thymic type; 3, of nonthymic type) within 315 days of observation. The analysis indicated a link between the susceptibility to lymphomagenesis and the marker D16Mit34 on chromosome 16. The mice heterozygous for the BALB/c and STS alleles at D16Mit34 were less sensitive to lymphomagenesis than the mice homozygous at this locus. There was no significant difference in latency among the genotypes. Our study showed the existence of a susceptibility locus for radiation lymphomagenesis on chromosome 16 and revealed aspects of the genetics of lymphoma susceptibility.

Animals↗
PubMed2000

Chronic myelomonocytic leukemia derived from a possible common progenitor of monocytes and natural killer cells.

The neural cell adhesion molecule, CD56, is expressed on acute myelogenous leukemia (AML) cells in 17-20% of the patients. However, the clinical and biological significance of its expression in AML has not been well analyzed from the standpoint of CD56 expression and its association with differentiation to a natural killer (NK) cell lineage. Here we present a 78-year-old patient with chronic myelomonocytic leukemia (CMML) whose leukemic cells had features of both monocytes and NK cells. We demonstrated that the leukemic cells were positive for CD4, CD56 and interleukin-2 (IL-2) receptor beta chain (CD112) in addition to myelomonocytic markers such as CD33, CD11b and CD11c. These leukemic cells proliferated well in vitro in response to 10-100 U/ml of IL-2, and functionally showed significant cytotoxicity against K562 target cells in a 4-hour (51) Cr release assay. All the above data indicate that these cells possessed at least some of the biological features of NK cells. Accordingly, we speculate that the leukemic cells in this patient may have been derived from a possible common progenitor of monocytes and NK cells.

Aged↗
PubMed2000

Midkine expression in Reed-Sternberg cells of Hodgkin's disease.

Midkine (MK) was originally cloned as a product of a retinoic acid-responsive gene. The rationale for studying MK expression is based on previous reports showing that it transforms 3T3 cells, and that it acts as an autocrine growth factor in Wilm's tumors, and that its overexpression has been associated with worse outcome in bladder carcinoma. Besides bladder carcinoma, its expression was reported in various solid tumors. We investigated the expression of MK protein and/or MK gene in biopsied specimens from 40 patients with primary malignant lymphoma, 21 with Hodgkin's disease (HD) and 19 with non-Hodgkin's lymphoma (NHL). Reed-Sternberg (R-S) cells were stained positive in 10 of 16 HD cases evaluated by immunohistochemical method, whereas 18 of 19 NHL cases did not stain, and one B-cell NHL stained weakly positive. Immunostaining analysis was extended to established cell lines and to normal lymphocytes with or without lectin stimulation or with EB virus transformation. Among hematopoietic cells examined, erythro- or megakaryoblastic leukemia cell lines (K562, MEG-01 and UT7) were positive, while normal lymphocytes (except the EB virus-transformed one) and most myeloid and lymphoid cell lines (except Raji cells) were negative. On the contrary, solid tumor cell lines showed high and strongly positive staining including cell lines derived from of lung gastric, colon, and a pancreatic cancer. Using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), which is suitable for the detection of weakly expressed mRNA, the relative ratio of MK mRNA to beta-actin mRNA of samples was measured and compared in cases where RNA was available. The mean values of relative ratio (MK/beta-actin) of HD were almost twice as those of NHL samples, peripheral blood T cells, and spleen B cells. Our findings showed that MK is expressed in Reed-Sternberg cells of HD, and that MK might play a role in the pathogenesis of HD.

Animals↗
PubMed2000

[Significance of reduction surgery for giant hepatocellular carcinoma with diffuse lung metastases and multiple intrahepatic metastases].

Continuous systemic infusion of low-dose cisplatin (CDDP) (10 mg/body/day) and 5-fluorouracil (5-FU) (500 mg/body/day) was performed for advanced hepatocellular carcinoma (HCC) after hepatectomy with diffuse lung metastases and multiple intrahepatic metastases. This infusion chemotherapy, cisplatin was continued for five days, and discontinued for two days, whereas 5-fluorouracil was administered every day and repeated four weeks as one course basally. Remnant metastases had almost disappeared after systemic chemotherapy for 10 weeks. In our experience, the response rate in 13 patients who underwent reduction surgery for multiple HCC was 84.6%. Continuous infusion of low-dose CDDP/5-FU may be effective in patients having absolute non-curative resection.

Adult↗
PubMed2000

[Hepatocellular carcinoma with tumor thrombus in the portal and hepatic veins treated successfully with hepatectomy and chemotherapy--a case report].

A 39-year-old woman was admitted to our hospital because of advanced hepatocellular carcinoma. She had good liver function with clinical Stage I. Abdominal ultrasonographic study and CT scan revealed a huge tumor of 12 cm in diameter in the left lobe of the liver, with tumor thrombi in the portal and hepatic veins. A chest CT scan demonstrated multiple bilateral lung metastases from 5 to 10 mm in size. An extended left hemihepatectomy with extirpation of the portal and hepatic venous tumor thrombi was performed. On postoperative day 7, low-dose cisplatin (10 mg/day-5 days/week) and 5-fluorouracil (250 mg/day-continuous for 7 days/week) were administered intravenously. Four weeks after chemotherapy, CT scan revealed no recurrence in the liver and no change in the lung metastases. The patient is now being treated on an outpatient basis with no change in the metastatic tumors.

Adult↗
PubMed2000

Clinicopathological analyses of 5 Japanese patients with CD56+ primary cutaneous lymphomas.

We analyzed the clinicopathological features of 5 Japanese patients with CD56+ primary cutaneous lymphomas (3 men and 2 women aged 25 to 73 years). Except for 1 patient in whom bone marrow involvement was simultaneously observed, all patients presented with cutaneous lesions. Based on their Epstein-Barr virus (EBV) status, we categorized these patients into 2 groups, namely EBV-encoded small RNA-1 (EBER-1) (3 patients) and EBER-1- (2 patients). Generalized lymphadenopathy and bone marrow involvement were observed only in EBER-1 patients. Morphologically, angiocentric proliferation was more prominent in EBER-1+ patients and was accompanied by panniculitis-like changes. The lymphomas in EBER-1- patients featured monomorphic proliferation of lymphoblastic cells with no cytoplasmic granules. Phenotypically, CD3-, cytoplasmic CD3 epsilon+, and CD56+ were common findings in both types. The EBER-1- type showed an additional distinguishing feature, CD7+, CD4+, CD8-, HLA-DR+, and terminal deoxynucleotidyl transferase-positive (TdT+) phenotype. The lymphoma was primarily resistant in the EBER-1+ type, and the patients died within 6 months of admission. In contrast, the lymphoma in the EBER-1- patients was originally chemosensitive. Collectively, we consider there to be at least 2 types of CD56+ primary cutaneous lymphomas, corresponding to nasal-type natural killer (NK)/T-cell lymphomas (EBER-1+) and blastic NK-cell lymphomas (EBER-1-).

Adult↗
PubMed1999

Neural restrictive silencer factor recruits mSin3 and histone deacetylase complex to repress neuron-specific target genes.

Accumulative evidence suggests that more than 20 neuron-specific genes are regulated by a transcriptional cis-regulatory element known as the neural restrictive silencer (NRS). A trans-acting repressor that binds the NRS, NRSF [also designated RE1-silencing transcription factor (REST)] has been cloned, but the mechanism by which it represses transcription is unknown. Here we show evidence that NRSF represses transcription of its target genes by recruiting mSin3 and histone deacetylase. Transfection experiments using a series of NRSF deletion constructs revealed the presence of two repression domains, RD-1 and RD-2, within the N- and C-terminal regions, respectively. A yeast two-hybrid screen using the RD-1 region as a bait identified a short form of mSin3B. In vitro pull-down assays and in vivo immunoprecipitation-Western analyses revealed a specific interaction between NRSF-RD1 and mSin3 PAH1-PAH2 domains. Furthermore, NRSF and mSin3 formed a complex with histone deacetylase 1, suggesting that NRSF-mediated repression involves histone deacetylation. When the deacetylation of histones was inhibited by tricostatin A in non-neuronal cells, mRNAs encoding several neuronal-specific genes such as SCG10, NMDAR1, and choline acetyltransferase became detectable. These results indicate that NRSF recruits mSin3 and histone deacetylase 1 to silence neural-specific genes and suggest further that repression of histone deacetylation is crucial for transcriptional activation of neural-specific genes during neuronal terminal differentiation.

3T3 Cells↗
PubMed1999

Expression of human inducible nitric oxide synthase gene in T-cell lines infected with human T-cell leukemia virus type-I and primary adult T-cell leukemia cells.

We examined the expression of messenger RNA (mRNA) of the human inducible nitric oxide synthase (hiNOS) gene in a panel of human T-cell lines. Reverse transcriptase-polymerase chain reaction showed that human T-cell leukemia virus type-I (HTLV-I)-infected T-cell lines (MT-1, SLB-1, and C5/MJ) expressed mRNA for the hiNOS, but TL-Om1 or uninfected Jurkat, H9, and CCRF-CEM did not. The MT-1, SLB-1, and C5/MJ cell lines are infected with HTLV-I and express the viral transactivator Tax, whereas TL-Om1 cells, although derived from adult T-cell leukemia (ATL) leukemic cells, do not express Tax. There was, thus, a correlation between Tax and hiNOS mRNA expression. The transcriptional regulatory region of the hiNOS gene was activated by Tax in Jurkat, in which endogenous hiNOS is induced by Tax. Deletion analysis showed that the region of hiNOS encompassing nucleotides -159 to -111 contained the minimum Tax-responsive elements. Mutations in the NF-kappaB element at position -115 and -106 bp in the hiNOS promoter were still activated by Tax, and a Tax mutant defective for activation of the NF-kappaB pathway retained the ability to activate the hiNOS promoter. In addition, overexpression of the dominant-negative mutants of IkappaBalpha and I kappaBbeta failed to reduce Tax-induced activation of hiNOS gene. Furthermore, hiNOS mRNA was detected in leukemic cells from ATL patients. Our results show that the hiNOS promoter contains a minimum Tax-responsive element located between nucleotides -159 and -111, and imply that the expression of the hiNOS gene is involved in the pathogenesis of HTLV-I-associated diseases.

Adult↗
PubMed1999

Induction of human beta-defensin-2 mRNA expression by Helicobacter pylori in human gastric cell line MKN45 cells on cag pathogenicity island.

Helicobacter pylori is an etiological agent of gastritis, peptic ulcer, and gastric cancer. Human beta-defensin-2 (hBD-2) is an antimicrobial peptide which belongs to one of the most important host defense systems against bacterial infection in several epithelial tissues. We studied the effect of H. pylori on the expression of hBD-2 mRNA in MKN45 gastric mucosal cells. H. pylori, but not culture filtrate, increased the hBD-2 mRNA level in MKN45 cells; the inductive effect of H. pylori was not detected with Intestine 407 cells. Among H. pylori strains, strain OHPC0002, which lacks a cag Pathogenicity Island (PAI), did not induce hBD-2 mRNA in MKN45 cells. These results suggested that H. pylori cag PAI is critical for the induction of hBD-2 mRNA in MKN45 cells. Exposure of MKN45 cells to Salmonella typhimurium, S. enteritidis, S. typhi, and S. dublin, but not Escherichia coli ML35, also resulted in induction of hBD-2 mRNA.

Blood Bactericidal Activity↗
PubMed1999

Difference in induction of uncoupling protein genes in adipose tissues between young and old rats during cold exposure.

Induction of uncoupling protein (UCP) genes in adipose tissues from young and old rats exposed to cold was compared. UCP1 mRNA expression in brown adipose tissue (BAT) was enhanced in both young and old rats after cold exposure, but the expression was downregulated at 72 h after the exposure only in the young rats. The UCP2 gene was induced notably in BAT of young rats instead of the downregulation of the UCP1 gene, whereas the induction in old rats was almost blunted. The pattern of UCP3 expression was similar to that of UCP1 expression in each group. The effect of cold exposure on the expression of UCP2 genes was also observed in white adipose tissue from the young rats. These results indicate a change in induction of UCP genes in adipose tissues with aging.

Adipose Tissue↗
PubMed1999

Childhood-onset schizophrenia and obstetric complications: a case--control study.

Obstetric complications (OCs) may be a risk factor for developing schizophrenia. In a recent study of a meta-analysis, the odds ratio for the development of the disorder in adulthood associated with OCs has been reported to be about 2.0 (i.e., a two-fold increase in risk). However, little attention has been paid to the involvement of OCs in risk of the development of childhood-onset schizophrenia. Therefore, the authors examined the relationship between OCs and childhood-onset schizophrenia. Thirty-three children, aged 8-13 years (average 12.4 years), meeting the DSM-III-R criteria for schizophrenia, were compared with controls (children with anxiety disorder) matched for sex and age. Childhood-onset schizophrenics showed significantly greater scores in all of the three measures of OCs according to Parnas et al.'s scale compared with controls. Moreover, those individuals exposed to OCs were 3.5 times as likely to develop schizophrenia as were those without OCs. The risk association between OCs and the disorder was far greater for male than for female schizophrenics. Our results, together with those in previous studies showing the association between OCs and adult-onset schizophrenia, suggest that childhood- and adult-onset schizophrenia may, at least in part, share a common neuropathogenesis.

Adolescent↗
PubMed1999

Silencer-mediated repression and non-mediated activation of BDNF and c-fos gene promoters in primary glial or neuronal cells.

Although the neuron-restrictive silencer element (NRSE/Regard) has been shown to function as a negative-acting DNA regulatory element to prevent the expression of neuron-specific genes in non-neuronal cells, little is known about its silencing effect on transcription in primary glial cells nor its effect on transcriptional activation in primary neurons. By DNA transfection in primary cultures of rat cortical neuronal or glial cells, we investigated the effect of NRSE on transcription mediated by the BDNF promoter I or c-fos promoter to which NRSE sequences derived from the SCG10 gene were linked. Transfection of plasmid DNAs to NIH3T3 fibroblasts resulted in a marked repressive effect of NRSE on BDNF promoter I- or c-fos promoter-mediated transcription. In primary neuronal cells, however, NRSE did not repress the basal promoter activities of BDNF and c-fos genes and allowed the transcriptional activation of these genes induced by membrane depolarization although NRSE slightly reduced the magnitude of BDNF promoter I activation. In contrast to neuronal cells, a marked repression of basal promoter activities of both genes was detected in primary glial culture and a two base pair-mutation of NRSE partially recovered the repression. These results indicate that NRSE negatively acts on its linked promoters in primary glial cells and does not interfere an activation of linked promoters in neuronal cells.

3T3 Cells↗
PubMed1999

Neuron-targeted gene transfer by adenovirus carrying neural-restrictive silencer element.

Adenovirus transfers genes to a wide range of cell types, but its application to neurons has been hampered by its reduced efficiency of infection as compared with that for glia. To achieve neuron-targeted gene transfer, we have produced an adenovirus carrying the reporter lacZ gene driven by the SCG10 minimum promoter containing the neural-restrictive silencer element (NRSE), which element selectively represses the transcription of genes in non-neuronal cells. When rat hippocampal slice cultures were infected with NRSE-bearing adenovirus, beta-galactosidase-positive cells were mostly pyramidal and granular neurons, whereas infection with virus carrying a mutated NRSE resulted in beta-galactosidase expression in both neurons and glia. The results suggest that the adenovirus carrying NRSE to be a useful tool for neurontargeted gene transfer.

Adenoviridae↗
PubMed1999

Modulations of glucocorticoid-induced apoptosis linked to the p53 deletion and to the apoptosis susceptibility gene Rapop1 (Radiation-induced apoptosis 1).

We have analysed the effects of p53 and of the apoptosis susceptibility gene Rapop1 (Radiation-induced apoptosis 1) located on chromosome 16 on glucocorticoid- and radiation-induced in vivo apoptosis of thymocytes. For those analyses, we used Rapop1 semicongenic mice heterozygous for the STS and BALB/cHeA alleles in the chromosomal segment containing Rapop1 in the BALB/cHeA background, mice bearing a p53 deficient allele in the BALB/cHeA background and the genetic crosses between these mice. The p53 wild type mice with a STS/A allele at the Rapop1 locus were less susceptible to both radiation- and glucocorticoid-induced apoptosis than those with homozygous BALB/cHeA alleles at this locus. Surprisingly, glucocorticoid-induced apoptosis was enhanced in the p53 hemizygous mice and considerably increased in the p53 nullizygous mice. In contrast, a sizable reduction of radiation-induced apoptosis was seen in the p53 hemizygous mice. The low susceptiblity to glucocortocoid-induced apoptosis linked to the STS allele of Rapop1 was less pronounced in the p53 hemizygous mice and a diminished effect of Rapop1 on radiation-induced apoptosis was seen in these mice. Although it remains to be established whether the genes modulating glucocortocoid-induced apoptosis are identical to p53 and Rapop1, our data suggest that p53 and Rapop1 may participate in glucocorticoid-induced apoptosis of thymocytes.

Animals↗
PubMed1999

Daily rhythm of serum melatonin levels and effect of light exposure in patients with dementia of the Alzheimer's type.

BACKGROUND: Several studies have suggested that patients with dementia experience a deterioration of biological rhythms. We investigated the daily profile of serum melatonin levels in patients with dementia of the Alzheimer's type (AD), since daily melatonin rhythm is thought to reflect the functioning of the biological clock. METHODS: Seventeen inpatients with AD, 10 psychiatric inpatients without dementia, and 11 elderly healthy volunteers participated in this study. Serum melatonin was assessed every 3 hours by radioimmunoassay. RESULTS: A daily fluctuation of melatonin levels with a significant nocturnal increase was observed in all three subject groups. However, both the AD patients and psychiatric patients without dementia showed significantly higher levels of melatonin in the daytime compared with the healthy subjects. When the effect of bright light exposure on melatonin secretion was investigated in six AD patients and five psychiatric patients without dementia, the daytime levels were markedly decreased in the patients without dementia, while no change was observed in the AD patients. CONCLUSIONS: The high levels of melatonin in the daytime associated with a lack of response to light exposure in AD patients may be due to the neurodegenerative process of this disease.

Aged↗