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Biomedical subjects

N Mori

Publications and source records attributed to N Mori.

At least 127 records · Page 7Linked to original sources

Molecular cloning of three homoeologous cDNAs encoding orthologs of the maize KNOTTED1 homeobox protein from young spikes of hexaploid wheat.

The plant knotted1 (kn1)-like homeobox genes are known to play important roles in the maintenance of shoot apical meristem (SAM), determination of cell fate and differentiation of vegetative tissues. To study structural diversity of the three homologous loci encoding a KN1-like homeobox protein in the hexaploid wheat genome, we isolated clones from a cDNA library of young spikes of Japanese common wheat cultivar 'Norin 26'. Three different but highly homologous cDNAs were isolated and their sequences were determined. The mean homology of the deduced amino acid sequences was 96% as compared to the barley ortholog KNOX3. The wheat kn1-like homeobox proteins named WKNOX1 are encoded by a single set of homologous genes on the homologous group 4 chromosomes in the three component genomes of common wheat, i.e. 4A, 4B and 4D. The nucleotide sequence data and the Southern blot pattern suggested that the three homologous loci of wknox1 genes are highly conserved through polyploid evolution of wheat. They were expressed in SAM-containing shoots and young spikes but not in developed leaves, glumes and lemmas and callus tissues. The ectopic expression of the wknox1 was observed in lemma of wheat Hooded (Hd) mutants. The result suggested that the Hd gene is a dominant allele of the wknox1 locus on chromosome 4A.

Amino Acid Sequence↗

D-beta-hydroxybutyrate protects neurons in models of Alzheimer's and Parkinson's disease.

The heroin analogue 1-methyl-4-phenylpyridinium, MPP(+), both in vitro and in vivo, produces death of dopaminergic substantia nigral cells by inhibiting the mitochondrial NADH dehydrogenase multienzyme complex, producing a syndrome indistinguishable from Parkinson's disease. Similarly, a fragment of amyloid protein, Abeta(1-42), is lethal to hippocampal cells, producing recent memory deficits characteristic of Alzheimer's disease. Here we show that addition of 4 mM d-beta-hydroxybutyrate protected cultured mesencephalic neurons from MPP(+) toxicity and hippocampal neurons from Abeta(1-42) toxicity. Our previous work in heart showed that ketone bodies, normal metabolites, can correct defects in mitochondrial energy generation. The ability of ketone bodies to protect neurons in culture suggests that defects in mitochondrial energy generation contribute to the pathophysiology of both brain diseases. These findings further suggest that ketone bodies may play a therapeutic role in these most common forms of human neurodegeneration.

1-Methyl-4-phenylpyridinium↗

Nasal natural killer cell lymphoma in a post-renal transplant patient.

Posttransplant lymphoproliferative disorders in organ allograft recipients are most commonly of B-cell origin and only occasionally of T-cell origin. We present here a case of nasal natural killer cell lymphoma associated with Epstein-Barr virus that occurred in a recipient of a renal transplant 4 years posttransplantation. Immunohistochemically, the lymphoma cells showed CD2-, surface CD3-, cytoplasmic CD3E+, CD56+, CD57-, CD16-, and CD43+ phenotype. Analyses of T-cell receptor beta and gamma genes showed germ line configurations. EBER-1 was detectable in the lymphoma cells. The patient was diagnosed as having natural killer cell lymphoma and was treated with six courses of combination chemotherapy for non-Hodgkin's lymphoma He has been in remission for more than 3 years thereafter. To the best of our knowledge, this is the first report of a posttransplant NK cell lymphoma associated with Epstein-Barr virus.

Adult↗

The SCG10-related gene family in the developing rat retina: persistent expression of SCLIP and stathmin in mature ganglion cell layer.

Neuronal growth-associated proteins (GAPs), such as GAP-43 and SCG10, are thought to play crucial roles in both axonal and dendritic outgrowth during neural development and regeneration, although the underlying mechanisms remain largely unknown. The recent finding that SCG10 is a microtubule regulator and also the identification of RB3 and SCLIP as two new SCG10-related members prompted us to investigate the roles of SCG10-related family in neural development, using the retina as a model system. We determined the temporal expression and the spatial distribution of SCG10-related mRNAs in the developing rat retina. Semiquantitative analysis by RT-PCR revealed that in prenatal retina, levels of SCG10 and stathmin mRNAs were higher than those of RB3 and SCLIP. In the postnatal retina, the level of SCLIP increased, whereas the level of RB3 remained low. In situ hybridization revealed that GAP-43 and all of the SCG10-related family mRNAs were present in the retinal ganglion cells (RGCs) at all stages of retinal development, and that stathmin mRNA was present in mitotic neuroblastic cells. Differential expression of SCG10 and other members of the family became more evident as retinal development proceeded; SCG10 and RB3 expression were relatively specific in the RGCs and amacrine cells, whereas SCLIP was also evident in bipolar and horizontal cells. Stathmin mRNA was highly expressed both in the RGCs and other interneurons. These results indicate that multiple SCG10-related proteins are expressed in single neurons including RGCs, and suggest that these nGAPs play similar but distinct roles in differentiation and functional maintenance of retinal neurons.

Animals↗

Alleviation of graft-versus-host disease after conditioning with cobalt-protoporphyrin, an inducer of heme oxygenase-1.

BACKGROUND: Recently, we demonstrated that elevated expression of heme oxygenase-1 (HO-1 or Hsp-32) resulted in the modulation of several immune effector functions. Here we evaluated whether induction of HO-1 after administration of cobalt protoporphyrin (CoPP) can prevent the development of acute graft-versus-host-disease (GVHD). METHODS: Acute GVHD was initiated by injection of unfractionated spleen cells from C57BL/6 into B6D2/F1 mice. RESULTS: Administration of CoPP resulted in increased survival: 85% of CoPP-treated animals survived for >100 days compared with only 29% of saline-treated control animals (P<0.05). In contrast, administration of ZnPP, a well-known inhibitor of HO, accelerated GVHD development. The protective effect of CoPP therapy seemed to be caused by immunomodulation of donor cells, because treatment of cell donors prevented development of acute GVHD in 80% of recipients compared with 0% in control animals. Spontaneous lymphocyte proliferation could be measured with splenocytes harvested from animals developing GVHD but not with splenocytes from recipients of CoPP-treated donor cells. CoPP-treatment had no effect on interleukin-2 or interleukin-4 synthesis but inhibited interferon-gamma production. Mice with active GVHD demonstrated a defective lympho-proliferative response to alloantigens or concanavalin A. However, spleen cells isolated from survivors (on day 100) responded normally. Flow cytometric analysis of splenic T cell populations revealed a severe reduction in recipient type (H-2b,d) cells in mice with active GVHD, whereas in protected mice the number of cells remained normal. CONCLUSION: The results from this study confirmed our previous observation that up-regulation of HO-1 activity is associated with down-regulation of several immune effector functions. This resulted in protection from acute GVHD in a parent into F1 mouse model.

Animals↗

Analysis of highly frequent allelic loss region on distal chromosome 12 in murine radiation-induced lymphomas.

Recent genetic studies of tumorigenesis have strongly suggested an existence of tumor suppressor gene(s) on murine chromosome 12 and human chromosome 14q32. We previously described that putative tumor suppressor gene(s) might reside between D12Mit53 and D12Mit233. We analyzed three genes, Tcl1, Yy1 and Tnfalphaip2, which had been mapped around the region, as the candidates in radiation lymphomagenesis of (BALB/c x MSM/Ms)F1 hybrid mice. The locus order and distances of the three genes and microsatellite loci were estimated as follows: [centromere] - Tcl1-(> or =0.085 cM)-D12Mit50-(0.085 cM)D12Mit132-(1.96 cM)D12Mit122-(0.085 cM)D12Mit53-(1.37 cM)-[D12Mit233,D12Mit279,Yy1]-(0.085 cM)-D12Mit181-(> or =0.17 cM)-Tnfalphaip2 - [telomere]. Allele losses at Tcl1, Yy1 genes and D12Mit233 were observed in 94(45%), 143(68%) and 147(70%) of 210 lymphomas, respectively. In semi-quantitative analysis of Yy1 mRNA levels by RT-PCR, kinetics of the yield of the Yy1-cDNA-specific PCR products showed almost the same profiles among thymic lymphomas with allelic loss at Yy1, lymphomas with both alleles retained and normal thymus. These results suggest that Tcl1, Yy1 and Tnfalphaip2 genes are not predominantly involved in radiation lymphomagenesis of mice. In further analysis of the common allelic loss region, we found new loci, Y152pR1 and Y184pR2, from YACs which located in the hot region between D12Mit53 and D12Mit233, and the highest frequency of allelic loss (71%) was observed at the Y184pR2 locus. The LOH patterns of individual lymphomas suggest that putative tumor suppressor gene(s) lies between Y152pR1 and Y184pR2.

Animals↗

Pathogenesis of retinoic acid-induced abnormal pad patterns on mouse volar skin.

BACKGROUND: Abnormal dermatoglyphs on human volar skin have been reported in many syndromes, but little is known about the pathogenesis. Patterns of pads on rodent limb volar skin are homologous to human dermatoglyphs. METHODS: In previous studies, we showed that transplacental exposure to teratogens induced abnormal pads in mouse fetuses. Moreover, teratogens caused abnormal pad patterns at levels below those that caused skeletal malformations. In this study, we examined morphology and cytokinetics in developing abnormal pads. Pregnant mice were treated with all-trans-retinoic acid at 20 mg/kg orally at embryonal day (E) 12.5 (vaginal plug = E0). The hindlimbs of the embryos were harvested and observed under a light microscope and by scanning electron microscopy. Cell proliferation and cell death were estimated by 5-bromo-2'-deoxyuridine (BrdU) labeling, Nile blue A vital staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). RESULTS: Retinoic acid induced aplasia of the fibular tarsal pad and supernumerary interdigital pads on hindlimbs. Cell proliferation was observed in the area of developing pad, but cell death was very rarely seen in either normal or abnormal pads. CONCLUSIONS: Retinoic acid disturbed pad patterning as a whole rather than individual pad formation.

Abnormalities, Drug-Induced↗

Influence of angiotensin-converting enzyme gene polymorphism on development of athlete's heart.

BACKGROUND AND HYPOTHESIS: Genetic influence on development of athlete's heart is uncertain. This study investigated whether angiotensin-converting enzyme (ACE) gene polymorphism influenced development of athlete's heart. METHODS: Forty-three participants in a 100-km ultramarathon were classified on the basis of ACE gene polymorphism into a deletion group (n = 26) and an insertion group (n = 17). Echocardiograms were recorded to determine left ventricular end-diastolic and end-systolic diameters, interventricular septal thickness, left ventricular posterior wall thickness, left ventricular mass, and ejection fraction. RESULTS: Left ventricular end-diastolic diameter (65.5 +/- 4.0 mm) and left ventricular mass (369.5 +/- 73.9 g) were significantly larger in the subjects with deletion than in those with insertion (57.4 +/- 4.2 mm, 306.5 +/- 93.7 g). However, no significant differences in the other parameters were noted. CONCLUSIONS: In long-distance runners, ACE gene polymorphism of the D/D and D/I genotypes has a stronger influence on left ventricular hypertrophy than polymorphism of the I/I genotype.

Adult↗

Three distinct auditory areas of cortex (AI, AII, and AAF) defined by optical imaging of intrinsic signals.

Using pure-tone sound stimulation, three separate auditory areas are revealed by optical imaging of intrinsic signals in the temporal cortex of the chinchilla (Chinchilla laniger). These areas correlate with primary auditory cortex (AI) and two secondary areas, AII and the anterior auditory field (AAF). We have distinguished AI on the basis of concurrent single-unit electrophysiological recording; neurons within the AI intrinsic signal region have short (<15 ms) onset-response latencies compared with neurons recorded in AII and the AAF. Within AI, AII, and AAF we have been able to define cochleotopic or tonotopic organization from the differences in intrinsic signal areas evoked by pure tones at octave-spaced frequencies from 500 Hz to 16 kHz. The maps in AI and AII are arranged orthogonal to each other.

Animals↗

MELAS with the mitochondrial DNA 3243 point mutation: a neuropathological study.

We performed a neuropathological examination of the central nervous system from seven autopsied patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Five of the seven cases were confirmed to have the mitochondrial DNA (mtDNA) 3243 point mutation. In addition to the changes reported previously, diffuse atrophy of the cerebral and cerebellar cortices, diffuse gliosis of cerebral and cerebellar white matter, and cactus formation of Purkinje cells were observed. Electron microscopy revealed accumulation of mitochondria in the cactus formations. These lesions are common in MELAS with the mtDNA 3243 point mutation, but cannot be explained solely by mitochondrial angiopathy, and suggest that intrinsic mitochondrial malfunction contributes to neuronal damage in MELAS pathology. Moreover, the pathological changes observed in the cerebellum suggest that cerebellar function should be evaluated more carefully at the clinical level.

Adult↗

Identification of paternal mitochondrial DNA sequences in the nucleus-cytoplasm hybrids of tetraploid and hexaploid wheat with D and D2 plasmons from Aegilops species.

Mitochondrial (mt) DNA structures were studied in 12 nucleus-cytoplasm (NC) hybrids of tetraploid and hexaploid wheat in which nuclear genomes of the recurrent paternal wheat parents were combined with D and D2 plasmons from Aegilops species. RFLP analysis of 15 mtDNA regions indicated the presence of the paternal sequences in six regions encompassing 11 structural genes in all the NC hybrids. PCR-RFLP analysis showed that one region (a nad3-orf156 region) consisted of a mixture of the maternal, paternal and novel paternal-like sequences. The presence of unexpectedly high levels of the paternal sequences was confirmed by random PCR cloning and sequencing of this region. PCR-RFLP analysis of the random clones further showed that the relative stoichiometry of the maternal and paternal sequences varied depending on the plasmons from the maternal parents and the nuclear backgrounds of the paternal parents. Our results suggest that the differential amplification of the paternal mtDNA sequences is under the control of NC interaction in these NC hybrids.

Base Sequence↗

Underexpression of neural cell adhesion molecule and neurotrophic factors in rat brain following thromboxane A(2)-induced intrauterine growth retardation.

Intrauterine growth retardation (IUGR) often results in clinical neurodevelopmental disorders. To clarify the influence of uteroplacental insufficiency on central nervous system development, we have created a model of IUGR in rats using maternal administration of synthetic thromboxane A(2). We investigated expression patterns of neural cell adhesion molecule (NCAM) and reelin in this model by semiquantitative competitive polymerase chain reactions. On postnatal day 2, NCAM expression was decreased in rat cerebral cortex, and reelin expression was decreased in hippocampus from levels in controls without maternal thromboxane exposure. No significant differences in NCAM expression were seen in hippocampus, nor did reelin expression differ in cerebral cortex between control and IUGR groups. We also examined expression of two neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). In cerebral cortex the IUGR group showed less BDNF and NT-3 expression than controls. Delay of neuronal migration and histological changes observed in our IUGR rats may be related to altered expression of these molecules.

Animals↗

A unique monoclonal antibody mNI-11 rapidly enhances spread formation in human umbilical vein endothelial cells.

We previously reported a novel monoclonal antibody (MAb), designated mNI-11, recognizing an adhesion-associated antigen distinct from any previously reported ones. In this article, this adhesion-associated antigen with a molecular weight of about 97 kDa was found to be strongly expressed on human umbilical vein endothelial cells (HUVECs) by fluorescence-activated cell sorter (FACS) analysis. Expression of this antigen on HUVECs was slightly increased in response to the exposure to tumor necrosis factor-alpha (TNF-alpha) or phorbol myristate acetate (PMA). As a biological function exerted by this antigen, it was of great interest that immobilized mNI-11 directly and rapidly enhanced the spread formation of HUVECs, whereas MAbs binding other adhesion-associated antigens such as mNI-58A (anti-CD11a), L130 (anti-CD18), L133.1 (anti-CD31), L178 (anti-CD44), L25.3 (anti-CD49d), or LB-2 (anti-CD54) did not carry such activity under the same conditions. The HUVECs spread formation enhanced by mNI-11 was completely blocked in the presence of a microfilament formation inhibitor, cytochalasin D (CyD), a Ca2+ calmodulin inhibitor, W-7, EDTA, and was partially blocked by a microtubule formation inhibitor, nocodazole, a protein kinase C (PKC) inhibitor, H-7, and a protein synthesis inhibitor, cycloheximide (CHX). However, a protein tyrosine kinase (PTK) inhibitor, genistein, did not affect the spread formation under the same conditions. Taken together, it was suggested that the spread formation of HUVECs enhanced by mNI-11 was mainly associated with the influx of Ca2+ and microfilament reorganization. In addition, the novel property associated with mNI-11 to enhance the spread formation of HUVECs was possibly mediated through its reaction against a unique epitope on HUVECs.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Lactacystin activates FLICE (caspase 8) protease and induces apoptosis in Fas-resistant adult T-cell leukemia cell lines.

Lactacystin (LC) is a specific inhibitor of the proteasome, and has recently been shown to induce apoptosis in certain cell lines. In the present study, we established Fas-resistant adult T-cell leukemia (ATL) cell subclones RSO4 and RST1 from their parental Fas-sensitive cell lines SO4 and ST1, and examined whether LC can overcome Fas resistance. LC completely inhibited proteasome function as determined by a peptidyl-MCA substrate (LLVY-MCA and LLE-MCA), and induced apoptosis in these cell lines irrespective of Fas sensitivity at low concentrations (approximately 10 microM). LC induced the activation of caspase 3 (CPP32/Yama) and caspase 6 proteases in an identical manner to Fas-mediated apoptosis. Moreover, LC induced the activation of caspase 8 (FLICE) protease, which is the initiator of the Fas-mediated apoptotic cascade. Synthesized proteasome inhibitory peptide MG-115 (ZLLnV-CHO) also induced apoptosis in these cell lines. These results indicated that proteasome inhibitors overcome Fas-resistance by bypassing the proximal part of the Fas signal. Inhibition of the proteasome function may be a new strategy for the treatment of ATL.

Acetylcysteine↗

Solar urticaria: report of two cases with augmentation spectrum.

Two adult Japanese patients with severe solar urticaria are reported. In both patients, an action spectrum existed in the visible light range, and an augmentation spectrum was demonstrated in the visible light range longer than the action spectrum. The augmentation phenomenon has rarely been documented, and in the previous reports, it was induced by preirradiation with the augmentation spectrum. In our cases, however, only postirradiation with the augmentation spectrum enhanced urticarial reactions.

Adult↗

Allelotype analysis of the myelodysplastic syndrome.

Myelodysplastic syndromes (MDS) are a group of clonal hematologic disorders found predominantly in the elderly. The molecular mechanisms underlying the development of MDS remain obscure. In order to begin to identify tumor suppressor genes involved in these disorders, we performed a detailed microsatellite allelotype of chromosomal deletions associated with MDS. DNAs from both bone marrow and peripheral blood of 32 MDS patients were studied using 84 highly informative microsatellite markers on all autosomal arms, excluding the short arms of the acrocentric chromosomes. A high percentage of loss of heterozygosity (LOH) was identified on chromosome 5q (40% of informative cases), 7q (45%), 17p (23%) and 20q (20%), which corresponds to the most common cytogenetic abnormalities reported in MDS. In addition, a high incidence of LOH (> or =20%) was observed on chromosomal arms which had not been previously reported including 1p (36%), 1q (35%), and 18q (23%). This extensive allelotype analysis focuses attention on several novel genomic regions that probably contain novel tumor suppressor genes whose loss of function contributes to the development of MDS.

Adult↗

Varied B-cell immunophenotypes of Hodgkin/Reed-Sternberg cells in classic Hodgkin's disease.

AIMS: Recent analyses have suggested that Hodgkin's or Reed-Sternberg (HRS) cells in most cases of classic Hodgkin's disease are derived from germinal centre B-cells. However, there is controversy over which B-cell antigens are expressed in HRS cells. METHODS AND RESULTS: We studied 51 cases of classic Hodgkin's disease to immunohistochemically characterize HRS cells for pan-B-cell markers and specific markers for plasma cells. HRS cells expressed CD20 (L26) in 18 cases (35%), CD19 (B4) in nine (18%) and CD79a (mb-1) in 13 (25%). Furthermore, HRS cells were positive for CD138 (B-B4) in 24 cases (45%) and for PCA-1 in 24 (45%). In 41 (80%) cases, HRS cells expressed more than one B-cell marker. We then subclassified cases into those positive for plasma cell markers (n = 27) (group 1) and those negative for them (n = 24) (group 2). The average age in group 1 (40 years) was younger than in group 2 (54 years) (P < 0.05). The percentage of nodular sclerosis (NS) subtype in group 1 (52%) was 1.5 times greater than in group 2 (33%) (P < 0.05). With regard to Epstein-Barr virus encoded small RNA (EBER) in-situ hybridization, 14 cases (64%) were positive in group 2, but only seven cases (31%) were positive in group 1 (P < 0.025). CONCLUSION: In most cases of classic Hodgkin's disease, HRS cells expressed later stage of B-cell development. We consider that two different clinicopathological groups may correlate with the two different expressions of B-cell markers.

Adolescent↗