Biomedical subjects

N Mori

Publications and source records attributed to N Mori.

At least 253 records · Page 14Linked to original sources

PubMed1998

[Clinical and bacteriological studies on panipenem/betamipron in pediatrics. Kanagawa Research Group for Infectious Diseases of Children].

Following its introduction into the market, PAPM/BP (panipenem/betamipron) was clinically studied in 188 evaluable cases out of 207 cases primarily of respiratory infectious diseases treated at the pediatric departments of 15 hospitals. In the clinical evaluation, the drug proved effective in three of three cases of sepsis; three of three cases of suppurative meningitis; nine of ten cases of laryngopharyngitis, six of seven cases of tonsillitis, 56 of 63 cases of acute bronchitis, 90 of 98 cases of pneumonia, and one of one case of phyothorax, all of which are respiratory infectious diseases; one of one case of secondary infection of a chronic respiratory disease; and two of two cases of lymphadenitis, which is a disease of the soft dermal structure. The overall efficacy rate was 91.0% (171/188 cases). In the bacteriological study, Gram-positive bacteria were eliminated in five of five strains of S. aureus, 30 of 31 strains of S. pneumoniae (96.8%), and three of three strains of S. pyogenes. Gramnegative bacteria were eliminated in 15 of 17 strains of H. influenzae (88.2%), three of four strains of M. catarrhalis, and two of two strains of K. pneumoniae. The overall elimination rate was 92.1% (70/76 strains). In the 23 strains of S. pneumoniae that were examined, penicillin-resistant strains accounted for 56.5%, showing an elimination rate of 100%. No serious adverse effects were observed, and the incidence of adverse effects was 1.45%. As for abnormalities in laboratory tests, levels of GOT and GPT increased in eight cases (3.88%), LDH increased in one case (0.48%), and neutropenia occurred in one case (0.51%). These results suggest that PAMP/BP could be considered the first choice in the treatment of infectious diseases in pediatrics, due to its effectiveness and high level of safety.

Adolescent↗

PubMed1998

Effect of acetazolamide on cation concentration in the endolymph of the endolymphatic sac.

Acetazolamide (ACTZ), a carbonic anhydrase inhibitor, has been reported to decrease the endolymphatic sac (ES) DC potential (ESP) in the guinea pig. To assess the involvement of cation transport in the ESP change by ACTZ we examined the effect of ACTZ upon the K+ and Na+ activities of the ES endolymph in the guinea pig using ion-sensitive microelectrode. ACTZ (10 mg/kg), a dose that produces the ESP maximum reduction, produced a significant increase in Na+ activity of the ES endolymph with no change in K+ activity. The results suggest that Na+ transport may be directly or indirectly involved in ESP reduction by ACTZ, and that a Na(+)-H+ exchanger may be involved in Na+ influx pathway from endolymph to the ES epithelial cells.

Acetazolamide↗

PubMed1998

Putative tumor suppressor gene region within 0.85 cM on chromosome 12 in radiation-induced murine lymphomas.

Analyses of genetic alterations in tumors from F1 hybrid mice produced by inter-subspecific crosses between genetically well-characterized inbred strains provide precise and comprehensive evidence for genetic abnormalities such as allelic loss. We performed loss of heterozygosity (LOH) analyses of 125 radiation-induced lymphomas of (BALB/cHeA x MSM/Ms)F1 hybrid mice by polymerase chain reaction (PCR) analysis of microsatellite DNA polymorphic markers. Very frequent LOH was found at a distal region on chromosome 12. To precisely define the most common region of LOH, we first determined the order of and distances between the available microsatellite loci around the region by using 586 (CXSD x MSM/Ms)F2 hybrid mice (1172 meiosis). The locus order and distances were [centromere]-D12Mit132-(0.34 cM)-D12Mit5O-(2.05 cM)-[D12Mit122, D12Mit53]-(0.85 cM)-D12Mit233-(0.43 cM)-D12Mit279-(O.17 cM)-D12Mit181-[telomere]. We then investigated the features of LOH at these loci. The highest frequency of LOH (83 of 125, 66%) was found at D12Mit233. The LOH patterns of individual lymphomas indicated that the most common region of LOH was within the 0.85 cM between D12Mit53 and D12Mit233, a region homologous to human chromosome 14q32.1. These results suggest that a putative novel tumor suppressor gene exists within this region.

Animals↗

PubMed1997

Repression of transcription from the human T-cell leukemia virus type I long terminal repeat and cellular gene promoters by wild-type p53.

Human T-cell leukemia virus type-I (HTLV-I), the etiologic agent of adult T-cell leukemia (ATL) transforms human T cells both in vivo and in vitro. However, the long latency period between infection and development of ATL, as well as the small fraction of the infected population that actually develops this disease, suggest that factors in addition to the virus are involved in its pathogenesis. Mutation of tumor suppressor gene p53 has been found in both HTLV-I-transformed T-cell lines and ATL cases at relatively low frequency. However, increasing evidence supports p53 functional impairment in HTLV-I-transformed T cells. Tax, the major transactivator of HTLV-I, is critical for the initial events involved in transformation. We have considered the possibility that p53 may regulate transcription of viral and cellular genes important for viral replication and transformation. Inactivation of p53 function might then permit constitutive expression of these viral and cellular genes. We have investigated the effects of wild-type and mutant p53 on Tax-mediated activation of the HTLV-I long terminal repeat (LTR) and the promoters of several cellular genes including the interleukin (IL)-1alpha, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF ), and IL-2 receptor alpha chain gene. Jurkat, HuT78, and U937 cells were cotransfected with plasmids containing a chloramphenicol acetyltransferase (CAT ) reporter gene under viral or cellular promoter control and the Tax expression vector, in addition to vectors for a wild-type or mutant p53. Wild-type p53 is a potent repressor of viral and cellular activation by Tax. Mutations within p53 severely inhibit this downregulation. We also show that wild-type p53 suppresses transcription from the HTLV-I LTR in Jurkat-Tax, a T-cell line stably expressing Tax, and MT-2, a HTLV-I-transformed T-cell line. Wild-type, but not mutant, p53 interfered with the binding of TATA-binding protein (TBP) to the TATA motif of the HTLV-I LTR. These results suggest that p53 inactivation may lead to upregulation of viral and cellular genes and may also be important for establishment of productive viral infection and development of ATL.

Gene Expression Regulation↗

PubMed1997

Upregulation of stathmin (p19) gene expression in adult rat brain during injury-induced synapse formation.

Stathmin (p19) is developmentally regulated as a neural-enriched phosphoprotein associated with neurite outgrowth and synaptic formation during cell proliferation and differentiation, and remains highly abundant in adult rat brain. Whether stathmin is involved in injury-induced reactive synaptogenesis in adult rat was examined in this study. Following unilateral cortical lesion, a significant increase in stathmin mRNA expression was found in the cells of contralateral homotypic cortex and in the subventricular zone of the lateral ventricle. This increase coincided in time with the corticostriatal axon sprouting and synaptic remodeling previously found in denervated striatum. Our data suggest that stathmin plays an important role in regulation of reactive synaptogenesis in adult brain.

Animals↗

PubMed1997

Anticipation and imprinting in schizophrenia.

Anticipation, i.e., a decrease in the age of onset and/or an increase in the severity of a disease in subsequent generations, and imprinting, i.e., different modes of parental transmission, have been suggested in trinucleotide repeat amplification diseases. The purpose of this study was to determine if anticipation and imprinting are associated with familial schizophrenia. Two generations of 49 schizophrenics from 24 families were studied. Ages of onset, numbers hospitalized, diagnostic subclasses of schizophrenia, amounts of antipsychotics, positive symptoms, negative symptoms, treatment resistance, and clinical course ratings, were compared between the two generations. The age of onset was significantly lower in the offspring generation, although there was no difference in the severity between the two generations. The negative symptom scores and clinical course scores in the offspring generation for paternal transmission were significantly higher than those for maternal transmission. Our results suggest the presence of imprinting and anticipation in schizophrenia.

Adolescent↗

PubMed1997

Allelotype analysis in the evolution of chronic myelocytic leukemia.

To elucidate the genetic events that may play important roles in the progression of chronic myelocytic leukemia (CML), we performed allelotype analysis in 30 patients with CML as the disease transformed to accelerated phase or blast crisis (21 myeloid and 9 lymphoid cases). DNAs were extracted from slides of bone marrow smears or from freshly isolated bone marrow mononuclear cells. The DNAs from the same individuals in both chronic phase and either blast crisis or accelerated phase were analyzed at 82 microsatellite markers, which mapped to each of the autosomal arms except the short arms of the acrocentric chromosomes. Loss of heterozygosity (LOH) on at least one locus was observed in 21 of the 30 cases (70%) as the disease progressed. Frequent allelic loss of > or = 20% of the informative cases was observed on chromosome arms 1p (35%), 7p (21%), 19p (20%), and 20q (29%). Allelic losses were also analyzed according to phenotypes. LOH of > or = 20% was detected on 1p (29%), 18p (20%), and 20q (27%) in myeloid blast crisis, and on 1p (50%), 4p (25%), 7p (43%), 9p (29%), 18q (25%), 19p (43%), and 20q (33%) in lymphoid blast crisis. Serial cytogenetic information was available for most of our cases with LOH on these arms, and only one case had loss of both chromosomes 9 and 20. Fractional allelic loss, calculated for each sample as the total number of chromosomal arms lost/total number of arms with information, showed a median value of 0.06 and a mean of 0.098 (range 0 to 0.60). These results suggest that tumor suppressor genes especially on 1p, 7p, 19p, and 20q probably have an important role in the progression to blast crisis of CML.

Adult↗

PubMed1997

Construction and overexpression of a synthetic gene for human DNA methylguanine methyltransferase: renaturation and rapid purification of the protein.

A synthetic gene was constructed that encodes human DNA methylguanine methyltransferase (hMGMT). The synthetic gene was designed with a number of unique restriction sites to facilitate cassette mutagenesis and to reflect the preferences found among genes in Escherichia coli. Both the full-length gene and a gene for a functional variant (hMGMT delta C) that lacks the C-terminal 28 codons were constructed, and the genes were overexpressed using a T7 RNA polymerase promoter. The proteins are made in the form of insoluble aggregates but the truncated form of the protein (hMGMT delta C) has been successfully denatured, renatured, and purified to near homogeneity by ion exchange. Methyltransferase activity assays of hMGMT delta C demonstrate that the reconstituted protein has substantial DNA repair activity, though somewhat less than full-length hMGMT that had been expressed and purified in a soluble form. Mass spectrometry of a mixture of proteolytic fragments confirmed the protein sequence and indicated no detectable oxidation of the active site cysteine. The protein was determined to be monomeric by gel filtration chromatography, and circular dichroism spectra for renatured hMGMT delta C and fully soluble hMGMT are consistent with the renatured protein preparation being fully folded. Refolded hMGMT delta C had a curious propensity to form large aggregates in a time-dependent manner when injected into a dynamic light scattering instrument; this aggregation behavior was not observed for hMGMT purified in a soluble form. Differences in susceptibility to aggregation may account for differences in methyltransfer activity. Yields of purified protein were approximately 5 mg/liter of culture.

Amino Acid Sequence↗

PubMed1997

Mapping of new recessive cataract gene (lr2) in the mouse.

A new strain of mice with cataracts was developed in BALB/cHeA and STS/A recombinant inbred strain, CXS4 (D). In this study the mapping of spontaneous autosomal recessive cataract mutation is described. This mutation was characterized by ruptures of the lens nucleus, vitreous chamber through the posterior capsule, and the vacuolization of the lens. For the linkage analysis, we produced two kinds of backcross progenies, (BALB/cHeA x D)F1 and (STS/A x D)F1 females crossed to D male mice. The gene (lr2, lens rupture2) was mapped to the central part of Chromosome(Chr) 14, 0.7 +/- 0.7 cM from the micosatellite marker D14Mit28.

Age Factors↗

PubMed1997

Molecular genetic approaches to the genes of longevity, aging and neurodegeneration in mammals.

Accumulative evidence suggests that species life-span is determined, at least in part, genetically. Recent cloning works using yeast (Saccharomyces cerevisiae) and worms (Caenorhabditis elegans) revealed several potential candidate genes, e.g. SIR4, a transcriptional silencing factor, and age-1, a putative signal transduction molecule, respectively, that may be involved in determining and/or regulating species life-span in lower organisms. It is, however, not clear yet whether mammalian homologs of these genes are also relevant to controlling longevity in higher organisms. In mice and humans several silencing factors are essential for cell-type specific gene expression. A variety of signal transducing molecules are also known to play important roles in mammals. I will briefly summarize recent progress in molecular genetic studies on such longevity-related genes, and discuss these results with our recent findings on a neural-selective silencing factor and a neural-specific signaling molecule that are important for functioning of the nervous system.

Aging↗

PubMed1997

Ligand-induced down-regulation of Trk messenger RNA, protein and tyrosine phosphorylation in rat cortical neurons.

Chronic exposure of brain neurons to nerve growth factor in vitro and in vivo results in increased levels of the nerve growth factor receptor TrkA. In contrast, in the present study, we have found that chronic exposure of rat embryonic cortical neurons to brain-derived neurotrophic factor (BDNF) leads to a pronounced reduction of the levels of protein and messenger RNA for the full-length but not the truncated BDNF receptor TrkB. Similar effects were observed with the other TrkB ligands neurotrophin-3 and neurotrophin-4/5. After pretreatment with BDNF, neurotrophin-3 or neurotrophin-4/5, subsequent tyrosine phosphorylation responses of the remaining Trks to the same factors were greatly reduced. Three days exposure of rat embryonic cortical neurons to BDNF induced an absolute refractory period of several hours, with no subsequent response to the same factor. Similar but less pronounced refractory effects were observed with neurotrophin-3 and neurotrophin-4/5. Our results suggest a negative regulatory effect of BDNF and other TrkB ligands on TrkB receptors. Down-regulation of the TrkB response by its ligands might play a role in the control of BDNF action during early development, when BDNF levels significantly increase. Our findings are also of potential clinical relevance, since the possibility of ligand-induced down-regulation of the receptor response needs to be addressed when considering BDNF or other neurotrophins for the therapy of neurodegeneration.

Animals↗

PubMed1997

Breast carcinoma with myeloid metaplasia--a case report.

A 49 year-old female had been suffering from primary myelofibrosis since February 1987 without receiving any treatment. In 1994, a breast mass was detected. Breast tumor biopsy revealed tubular carcinoma with intraductal components and multinucleated giant cells in the loose and myxoid stroma. The giant cells were thought to be megakaryocytes because both Factor VIII and platelet glycoprotein GP IIIa were detected in their cytoplasm. While additional mastectomy specimens and the axillary lymph nodes also revealed prominent myeloid metaplasia, there was no proliferation of the cancer cells. Granulocytic series stained for chloroacetate esterase and very few erythrocytic series were observed. This is the first case in which breast carcinoma and myeloid metaplasia coexisted in the same breast tumor.

Adenocarcinoma↗

PubMed1997

Hydrogen peroxide augmentation in a rat striatum after methamphetamine injection as monitored in vivo by a Pt-disk microelectrode.

We fabricated a Pt-disk microelectrode (diameter 30 microns) to conduct differential double-pulse amperometry (first step: 750 mV, 1 s; second step: 1,100 mV, 1 s) to detect hydrogen peroxide in the brain of a freely moving animal. This measurement determined hydrogen peroxide (detection limit, 0.03 microM) without any observable influence from other oxidizable species, such as dopamine (DA), ascorbic acid, or uric acid. The electrode was implanted into the right striatum of a rat. After intraperitoneal injection of methamphetamine (MAP), hydrogen peroxide concentrations were directly detected while the behavioral changes were monitored. MAP injection led to significant augmentation of hydrogen peroxide, the elevation of which depended on the dose of MAP. This is consistent with a previous report on the increase of DA-release caused by amphetamines and indirect evidence of the production of hydrogen peroxide via DA-metabolism.

Animals↗

PubMed1997

Absence of microsatellite instability during the progression of chronic myelocytic leukemia.

Microsatellites are highly polymorphic, short-tandem repeat sequences dispersed throughout the genome. To test the occurrence of genetic instability in the progression of chronic myelocytic leukemia (CML), we studied microsatellite instability (MSI) in 17 patients with CML. The DNAs from both chronic phase and blast crisis were analyzed at 10 loci. No MSI was observed in any of the 17 cases of blast crisis. These results indicate that MSI is rare and is not associated with progression to blast crisis in most cases of CML.

Blast Crisis↗

PubMed1997

Effects of intestinal stasis on intercellular adhesion molecule 1 expression in the rat: role of enteric bacteria.

BACKGROUND & AIMS: The mechanisms underlying the inflammatory changes associated with intestinal stasis are poorly understood. The objective of this study was to assess whether endothelial expression of intercellular adhesion molecule 1 (ICAM-1) and leukocyte recruitment are altered after intestinal stasis. METHODS: ICAM-1 expression and granulocyte recruitment were quantified in different tissues of Sprague-Dawley rats using the double-radiolabeled monoclonal antibody technique and peroxidase activity, respectively. RESULTS: Both constitutive and endotoxin-induced ICAM-1 expression were significantly higher in the cecum than in distal colon, a finding that cannot be explained by a difference in endothelial surface area between the two organs. Surgical procedures to improve cecal stool flow (cecostomy, ileocecostomy) elicited a significant decrease in constitutive ICAM-1 expression in both cecum and distal colon. Tissue peroxidase activity was normally higher in cecum than in distal colon, and this difference was significantly reduced by ileocecostomy. Oral administration of antibiotics (kanamycin and/or metronidazole for 2 days) significantly reduced constitutive ICAM-1 expression in the cecum, but not in the distal colon. CONCLUSIONS: This study indicates that intestinal stasis is associated with an increased expression of ICAM-1 and granulocyte infiltration, which may be mediated by enteric bacteria.

Animals↗

PubMed1997

Immunohistochemical study of necrotizing lymphadenitis: a possible mechanism for apoptosis involving perforin and granzyme-producing cytotoxic T cells.

Twelve lymph node specimens with necrotizing lymphadenitis and which had florid necrotic lesions were studied immunohistochemically. The majority of viable lymphoid cells in the necrotic foci were CD8+ lymphocytes and KP1+ or PGM1+ phagocytizing macrophages. The CD8+ T cells were Leu1+, Leu2+, Leu3-, Leu4+, Leu5b+, Leu7-, Leu11b- and Leu19-, indicating a suppressor/cytotoxic T cell phenotype. In addition, the cytoplasm of these cells was immunoreactive for perforin and granzyme B in a granular pattern. With a nick end-labeling technique, fragmented nuclei and some lymphoid cell nuclei were positively stained. These results suggest that the necrosis in necrotizing lymphadenitis is apoptotic necrosis of T cells targeted by CD8+, perforin and granzyme-producing, activated cytotoxic T cells, supporting a viral infection etiology.

Apoptosis↗

PubMed1997

High levels of the DNA-binding activity of E2F in adult T-cell leukemia and human T-cell leukemia virus type I-infected cells: possible enhancement of DNA-binding of E2F by the human T-cell leukemia virus I transactivating protein, Tax.

Transcription factor E2F binds to cellular promoters of certain growth- and cell cycle-controlling genes and forms distinct heteromeric complexes with other nuclear proteins. It has therefore been proposed that E2F is involved in cellular proliferation control. Human T-cell leukemia virus type I (HTLV-I) is an etiological agent of adult T-cell leukemia (ATL). We show here by mobility-shift assay that E2F-containing DNA-binding complexes were detected in HTLV-I-infected T-cell lines and leukemic cells obtained from ATL patients but not in an uninfected T-cell line, Jurkat, and normal peripheral blood mononuclear cells. The Tax protein, encoded by HTLV-I, is a potent transcription activator of viral and several cellular genes. We demonstrate that expression of Tax can induce the E2F-containing DNA-binding complexes in Jurkat T cells. Thus, Tax, through enhancement of the DNA-binding activity of E2F, may be capable of regulating cellular gene expression implicated in the proliferation and transformation of T cells in ATL. This activity may be relevant to the mechanisms whereby HTLV-I which does not contain oncogenes induces neoplasia.

Adult↗

PubMed1997

Activation of the interleukin-10 gene in the human T lymphoma line HuT 78: identification and characterization of NF-kappa B binding sites in the regulatory region of the interleukin-10 gene.

Interleukin-10 (IL-10) is a pleiotropic cytokine which has potent inhibitory effects on macrophages and T cells, and contributes to the regulation of proliferation and differentiation of B cells. Resting HuT 78, a T-cell line derived from a Sezary lymphoma, produced significant amounts of IL-10 compared with another T-cell line, Jurkat. To elucidate the mechanisms by which the IL-10 is expressed, we have analyzed their activity in human T-cell lines. We report here evidence that members of the family of transcription factors nuclear factor-kappa B (NF-kappa B)/Rel can specifically recognize 3 identical sequences located in the 5'-regulatory region of IL-10 gene in resting HuT 78 cells, whereas Jurkat cells expressed high levels of NF-kappa B consisting of p65 and p50 only upon activation with tumor necrosis factor-alpha (TNF-alpha). In HuT 78 cells, p50 was the major component in the NF-kappa B complexes. Exogenous TNF-alpha and the monoclonal antibody to TNF-alpha did not affect IL-10 production and constitutive NF-kappa B binding levels in HuT 78 cells. This study is the first demonstration of a role for NF-kappa B in the IL-10 gene expression, and suggests that its expression does not require TNF-alpha. These novel findings may account for the specific IL-10 gene expression in T cells.

Antibodies, Monoclonal↗