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Biomedical subjects

N Mori

Publications and source records attributed to N Mori.

At least 325 records · Page 18Linked to original sources

Genetic dissection of susceptibility to radiation-induced apoptosis of thymocytes and mapping of Rapop1, a novel susceptibility gene.

Genetic dissection of susceptibility to radiation-induced apoptosis of thymocytes was performed by counting dead cells in histologically processed thymuses after 0.5 Gy of whole-body X-irradiation, using recombinant congenic (CcS/Dem) strains derived from inbred mouse strains BALB/cHeA (susceptible) and STS/A (resistant). A high (8/20) number of strains with lower dead cell scores than BALB/cHeA among CcS/Dem recombinant congenic strains (RCS), which contain 12.5% of STS/A genome in the genetic background of BALB/cHeA strain, indicates that the difference between BALB/cHeA and STS/A is caused by several genes and that susceptibility probably requires BALB/cHeA alleles at more than one locus. Similar results were obtained with CXS/Hg recombinant inbred (CXS/Hg) strains. Analysis of F2 hybrids between BALB/cHeA and CcS-7, one of the CcS/Dem strains that showed lower dead cell scores than BALB/cHeA, demonstrated that a novel gene (Rapop1, radiation-induced apoptosis 1) controlling susceptibility to radiation-induced apoptosis in the thymus is located in the proximal region of mouse chromosome 16.

Animals↗

Cyclin I: a new cyclin encoded by a gene isolated from human brain.

A new member of the cyclin family has been isolated from an equalized cDNA library derived from human forebrain cortex. This putative cyclin, designated cyclin I, contains a typical cyclin box near the N-terminus and a PEST sequence near the C-terminus. Cyclin I shows the highest sequence similarity in the cyclin box to cyclins G and E, while the similarity between cyclins I and G also extends toward the C-terminus from the cyclin box. Cyclin I mRNA was expressed at high levels in postmitotic tissues, including skeletal muscle, heart, and brain, and was expressed constantly during cell cycle progression. The expression of cyclin I mRNA does not correlate directly to the cell cycle, and therefore cyclin I may be a novel cyclin member that functions independently of the cell cycle control.

Adult↗

Overexpression of mitochondrial genes in alloplasmic common wheat with a cytoplasm of wheatgrass (Agropyron trichophorum) showing depressed vigor and male sterility.

An alloplasmic hybrid (nucleus-cytoplasm hybrid) of common wheat (Triticum aestivum) with a cytoplasm of wheatgrass (Agropyron trichophorum) shows highly depressed vigor and complete male sterility. The presence of one short-arm telocentric homeologous group 1 chromosome (telosome) of the cytoplasm donor, however, restores normal vigor and male fertility of the hybrid. To study role(s) of the telosome on vigor/fertility restoration, mitochondrial genome organization and gene expression were compared among seedlings of the alloplasmic line showing depressed vigor, the corresponding restored line having a pair of the telosomes, and a euplasmic nuclear donor as control. No differences were detected in the mitochondrial genome structure between the depressed line and the restored line. Northern blot analysis using ten mitochondrial genes as probes showed no differences in transcript size and number between the depressed and restored lines, although clear differences were found in size of the major transcripts of two genes (cob and orf25) between the alloplasmic lines and the euplasmic control. Steady-state transcript levels were higher in the depressed line than in the other lines for all the mitochondrial genes analyzed including rrn18&5 when the same amount of mitochondrial RNA was loaded. The amount of rrn18&5 transcript in the total cellular RNA, however, did not differ among the lines. Run-on transcription analysis demonstrated markedly elevated transcriptional activities of all the mitochondrial genes analyzed in the depressed line based on unit amount of mitochondrial DNA, RNA and protein. The presence of Agropyron telosomes apparently normalized the level of mitochondrial transcription. These observations suggest either direct or indirect association of the observed mitochondrial gene overexpression with the depressed vigor and male sterility of the alloplasmic hybrid.

Amanitins↗

The action of substance P methyl ester on cochlear potentials in the guinea pig.

The action of the substance P agonist, substance P methyl ester (SPME) on cochlear potentials was examined in the guinea pig. Previous studies have shown that SPME is a selective agonist for neurokinin 1 (NK1) receptor. Perfusion with SPME at a concentration of more than 10(-6)M produced an increase in the amplitudes of the compound action potential and negative summating potential in a dose-dependent manner. N1 latency showed a tendency to be shortened, but this change was not significant. Amplitudes of the cochlear microphonics and endocochlear potential remained unchanged. Substance P fragment 7-11, an inactive analogue, produced no changes in the cochlear potentials. In contrast, the substance P antagonist [D-Pro2, D-Trp7,9]-SP blocked the action of SPME on the cochlear potentials. These results suggest that substance P may modulate neurotransmission through NK1 receptors in the cochlea.

Action Potentials↗

Adenosquamous carcinoma of the pancreas.

A 58-year-old Japanese man was admitted complaining of abdominal pain. An abdominal computed tomography examination demonstrated a tumor in the head of the pancreas and multiple calcifications. A laparotomy was performed and the tumor was removed by Whipple's operation. Histologically, the neoplasm that invaded the duodenal wall and the papilla of Vater was composed of nests of malignant squamous cells with intercellular bridges and showed the formation of keratinized pearls with a small area of concurrently neoplastic glandular and squamous elements. On the basis of these features, the diagnosis of adenosquamous carcinoma of the pancreas was made. The patient died 18 months after the operation. The neoplastic behavior of this rare primary pancreatic carcinoma is similar to that of duct cell carcinoma as well as pure squamous cell carcinoma of the pancreas. As the pancreas can be the target of metastases of squamous carcinomas from other organs it is wise to be aware of this rare entity.

Carcinoma, Adenosquamous↗

Endothelin-1 and big endothelin-1 increase in human endometrium during menstruation.

OBJECTIVES: Although the physiologic and pathologic roles of endothelin-1 in reproduction have been investigated, little is known about human uterine tissue levels. We studied the levels of immunoreactive endothelin-1 and immunoreactive big endothelin-1 in human endometrium and myometrium during each menstrual phase. STUDY DESIGN: Materials were obtained at hysterectomy (endometrium, n = 33; myometrium, n = 27). We measured immunoreactive endothelin-1 and immunoreactive big endothelin-1 by radioimmunoassay and performed an immunohistochemical study of the tissue. Data were analyzed by the Mann-Whitney U test. RESULTS: We detected larger amounts of immunoreactive endothelin-1 and immunoreactive big endothelin-1 in the endometrium than in the myometrium throughout the menstrual, proliferative, and secretory phases. Endometrial immunoreactive endothelin-1 and immunoreactive endothelin-1 were significantly increased in the menstrual phase (endothelin-1 68.8 +/- 23.3 pg/mg protein, n = 5, p < 0.005; big endothelin-1 45.2 +/- 5.7 pg/mg protein, n = 5, p < 0.003) compared with the other phases (endothelin-1 30.7 +/- 9.5 and 30.5 +/- 14.0 pg/mg protein; big endothelin-1 19.9 +/- 6.7 and 24.1 +/- 7.4 pg/mg protein). Immunohistochemistry demonstrated that the endometrial stromal cells were positive for antiendothelin monoclonal antibody only in the premenstrual and menstrual phases. CONCLUSION: Levels of immunoreactive endothelin-1 and immunoreactive big endothelin-1 are different in each type of uterine tissue and in each phase of the menstrual cycle. These changes may indicate some role of endothelin-1 in menstruation.

Antibodies↗

Mutations of the p53 gene in myelodysplastic syndrome and overt leukemia.

We analysed p53 mutations in 24 patients with myelodysplastic syndrome (MDS) and overt acute myeloid leukaemia after a period of MDS, using polymerase chain reaction-single strand conformation polymorphism analysis. In exons 5 to 8, mobility shifts were detected in five of the 24 patients. Sequence analysis was subsequently performed, and four missense mutations (16.7%) and one silent nucleotide substitution were identified. Patients harbouring mutations were characterized as having advanced disease. Loss of the wild type allele was observed in three of the four patients with missense mutations. No mobility shifts of the N-ras or FMS gene were detected in these four patients. We next analysed the correlation of the p53 mutations with the progression of MDS in three patients. The mutation was accompanied by the progression in two of the three patients. These findings suggest that mutations of the p53 gene are associated with progression in some cases of MDS, while being compatible with stable disease or clonal evolution in others.

Base Sequence↗

Differential regulation of catalytic and non-catalytic trkB messenger RNAs in the rat hippocampus following seizures induced by systemic administration of kainate.

Ribonuclease protection analysis and quantitative in situ hybridization histochemistry were used to investigate the coordination and regional expression of catalytic and non-catalytic trkB messenger RNAs in the adult rat hippocampus following systemic kainate-induced seizures. Changes in trkB expression were compared with the messenger RNA expression of its neurotrophic ligands, brain-derived neurotrophic factor and neurotrophin-3. TrkB messenger RNA expression was increased in the dentate granule cells at 1-4 h following the onset of seizures, and returned to control levels 16-24 h thereafter. In addition, seizures also induced expression of trkB messenger RNA in putative non-neuronal cells at four to seven days in the molecular layer of the dentate gyrus and the stratum lacunosum moleculare of the CA1 region. Hybridization with probes specific for the non-catalytic trkB receptor and the catalytic trkB receptor revealed that the increases at four and seven days in the molecular layers of the hippocampus reflected an up-regulation of only the non-catalytic form of the receptor. Furthermore, the neuronal increases observed 1-4 h were due to an up-regulation of both trkB TK- and trkB TK+ messenger RNAs. It was established that systemic administration of kainate increased brain-derived neurotrophic factor messenger RNA levels in the pyramidal and granule cell regions of the hippocampus 1-4 h following the onset of behaviorally manifested seizure activity. Early changes in neuronal expression of trkB TK- and trkB TK+ messenger RNA paralleled changes in brain-derived neurotrophic factor messenger RNA in the dentate granule cell and CA1 pyramidal cell layers, but not in the CA3 subregion. These data suggest that concomitant regulation of brain-derived neurotrophic factor and its cognate receptor may play a role in the selective vulnerability of hippocampal subregions to kainate-induced neuropathology. Furthermore, these data suggest a dual function for trkB receptor expression in the hippocampus following kainate-induced seizures, possibly related to both the plastic and degenerative consequences of seizure induction by kainate.

Animals↗

Role of endolymphatic anion transport in forskolin-induced Cl- activity increase of scala media.

To determine the role of anion transport in the forskolin-induced Cl- increase of scala media (SM), effects of forskolin on the EP (endocochlear potential) and Cl- activity (ACl) in SM were examined with double-barrelled Cl(-)-selective microelectrodes. The experiments were carried out on guinea pig cochleae, using a few anion transport inhibitors: IAA-94 for a Cl- channel blocker, bumetanide (BU) for an Na+/K+/2Cl- cotransport blocker, and SITS and DIDS for Cl-/HCO3- exchange blockers. The application of forskolin (200 microM) into scala vestibuli (SV) caused a 20 mEq increase of endolymphatic ACl and a 15 mV elevation of EP, and IAA-94 with forskolin completely abolished these responses. Although each application of BU, SITS or DIDS did not completely suppress EP elevation, the concurrent application of these inhibitors completely suppressed EP with endolymphatic ACl increase. The results indicate the involvement of Cl- channels, Na+/K+/2Cl- cotransport and Cl-/HCO3- exchange in forskolin-induced increase of ACl and EP. The role of adenylate cyclase activation and Cl- transport in endolymph homeostasis was discussed.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

The effect of protein kinase C stimulator and inhibitor on cochlear potentials in the guinea pig.

To determine a possible role of protein kinase C (PKC) in the cochlear, the effects of a PKC stimulator (phorbol-12-myristate-13-acetate; PMA), an inactive analogue of PKC stimulator (4 alpha-phorbol-12,13-didecanoate; 4 alpha-PDD) and a PKC inhibitor (D-sphingosine) on cochlear potentials were examined in the guinea pig. The perilymphatic perfusion with PMA (3 x 10(-6) M) produced an increase in compound action potential (CAP) amplitude and no change in N1 latency, the amplitudes of negative summating potential (-SP), cochlear microphonics (CM) and endocochlear potential (EP). The perfusion with 4 alpha-PDD (3 x 10(-6) M) did not change the sound-evoked cochlear potentials and the EP. The perfusion with D-sphingosine (10(-5) M) produced a decrease in CAP amplitude and no change in N1 latency and the amplitudes of -SP, CM and EP. The results suggest that PKC may be involved in the mechanism underlying the CAP generation.

Acoustic Stimulation↗

Role of ATP-sensitive K+ channels in anoxia-sensitive negative potential of endolymph.

To investigate the possible role of the ATP-sensitive K+ channels (KATP channels) in the generation of the anoxia-sensitive negative potential (ASNP), the effects of the treatment with glybenclamide and diazoxide on the endocochlear potential (EP) and K+ activity (AK) in the scala media were examined with double-barrelled K(+)-selective microelectrodes. The experiments were carried out in guinea pig cochleae, using glybenclamide as a KATP channel blocker and diazoxide as a KATP channel opener. Perilymphatic perfusion of glybenclamide decreased the amplitude of the ASNP and shortened its duration, whereas perfusion of diazoxide increased ASNP amplitude and prolonged its duration. Glybenclamide enhanced the decrease of endolymphatic AK by anoxia, whereas diazoxide suppressed this AK decrease. The results suggest that KATP channels may be involved in the generation of the ASNP.

Adenosine Triphosphate↗

Detection of mRNA encoding guanylate cyclase A/atrial natriuretic peptide receptor in the rat cochlea by competitive polymerase chain reaction and in situ hybridization.

Expression of mRNA encoding guanylate cyclase A (GC-A)/atrial natriuretic peptide (ANP) receptor in the rat cochlea was examined by polymerase chain reaction (PCR) and in situ hybridization (ISH). After reverse-transcription, PCR amplification, subcloning, and sequencing, we found that GC-A mRNA with sequence identical to that previously cloned from the rat brain (Chinkers et al., 1989) was expressed in the rat spiral ligament as well as in the spiral ganglion. However, GC-A mRNA was not detected in the stria vascularis. Competitive PCR using internal standard DNAs indicated that the expression of GC-A in the cochlea occurred at a level approximately 16 times less than that measured in kidney cortex. ISH histochemistry using a 35S-labeled antisense riboprobe showed the highest level of expression of GC-A mRNA to be in oligodendrocytes of the cochlear nerve root. The results suggest that ANP may play a role in the cochlear nerve function.

Amino Acid Sequence↗

Reduced expression of the molecular markers of dopaminergic neuronal atrophy in the aging rat brain.

Expression of mRNAs encoding the dopamine transporter (DAT) and tyrosine hydroxylase (TH) in dopaminergic neurons of the substantia nigra (SN) was examined in young and aged Fischer 344 rats by in situ hybridization. Quantitative analysis revealed a statistically significant decline in both DAT and TH mRNA expression in 24-month-old rats in comparison to 6-month-old rats. In addition, it was noted that DAT mRNA expression tended to decrease by 18 months, while TH mRNA reduction did not occur until 24 months. The age-related loss of DAT and TH mRNA expressions was accompanied by diminished expression of mRNA for a neuronal growth-associated protein GAP-43, but not for SCG10 or alpha 1-tubulin. The loss of GAP-43 mRNA became evident when both DAT and TH gene expression declined with advanced age. Our findings indicate that DAT may be a marker of atrophy in dopamine neurons during normal aging.

Aging↗