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T Komori

Publications and source records attributed to T Komori.

At least 127 records · Page 7Linked to original sources
PubMed1998

Transcriptional regulation of osteopontin gene in vivo by PEBP2alphaA/CBFA1 and ETS1 in the skeletal tissues.

Osteopontin (Opn) and polyoma enhancer-binding protein (PEBP) 2alphaA/core binding factor (CBFA) 1 have been suggested to play important roles in ossification. The overlapping localization of opn and PEBP2alphaA/CBFA1 mRNA, and the marked decrease of opn mRNA expression in PEBP2alphaA knockout mice, indicated that the transcription of opn gene was controlled by PEBP2alphaA. In the present study, we determined the direct regulation of PEBP2alphaA on the opn promoter activity. Opn promoter activity was markedly enhanced by PEBP2alphaA and ETS1 in a synergistic manner. The synergistic effect was diminished when either the PEBP2alphaA or ETS1 binding site was mutated, or the spatial arrangement of these sites was mutated by a 4-nt insertion. The distance between these sites was important for transactivation but not protein-DNA binding. The direct interaction between PEBP2alphaA and ETS1 was depended on protein-DNA binding. These results suggested that the specific spatial arrangement of both sites and direct interaction between PEBP2alphaA and ETS1, were essential for promoter function. Furthermore, endogenous opn mRNA was decreased with the introduction of dominant negative PEBP2alphaA to MC3T3/E1 cells expressing endogenous PEBP2alphaA, ETS1 and opn. These findings suggest that PEBP2alphaA and ETS1 cooperate in vivo to regulate expression of the opn gene in the skeletal tissue. Cell type-specific regulation of Opn gene expression will also be discussed.

3T3 Cells↗
PubMed1998

Growth disturbance in fetal liver hematopoiesis of Mll-mutant mice.

The MLL (ALL-1, HRX) gene is frequently involved in chromosomal translocations in acute leukemia and has homology with Drosophila trithorax, which controls homeobox gene expression and embryogenesis. To elucidate the function of Mll, we generated mice with a mutated Mll locus. Mice with a homozygous mutation were embryonic lethal and died at embryonic day 11.5 to 14.5, showing edematous bodies and petechiae. Histological examination revealed that hematopoietic cells were decreased in the liver of homozygous embryos, although they were composed of erythroid, myeloid, monocytic, and megakaryocytic cells with normal differentiation. Colony-forming assays using cells from fetal livers and yolk sacs showed that the number of colonies was markedly reduced and many of the colonies delayed to be recognized in Mllmu/mu embryos, although some of the colonies from Mllmu/mu embryos developed similarly with that from Mll+/+ and Mll+/mu embryos, suggesting the delayed onset of the proliferation of hematopoitic precursors. These data show that the hematopoietic precursors were greatly reduced in mutant mice, and suggest that Mll functions as a regulator of the growth of hematopoietic precursors.

Animals↗
PubMed1998

Presence of Cu/Zn superoxide dismutase (SOD) immunoreactivity in neuronal hyaline inclusions in spinal cords from mice carrying a transgene for Gly93Ala mutant human Cu/Zn SOD.

This investigation deals with the immunocytochemical localization of Cu/Zn superoxide dismutase (SOD) in the spinal cord neurons of transgenic mice that overexpress Gly93Ala mutant human Cu/Zn SOD and demonstrate clinicopathological features similar to human amyotrophic lateral sclerosis (ALS) with Cu/Zn SOD mutation. At low magnification of light microscopy, the gray and white matter of the spinal cord of Gly93Ala mice showed more intense Cu/Zn SOD immunoreactivity than that of control mice. At higher magnification, the cytoplasm of control mice neurons displayed a distinct staining for Cu/Zn SOD, whereas the surrounding neuropil was only weakly stained. In contrast, the intensity of Cu/Zn SOD immunoreactivity in the cytoplasm of the majority of Gly93Ala mice neurons was similar to that in the neuropil. Almost all neuronal hyaline inclusions (NHIs) of Gly93Ala mice were positively immunostained by antibodies to Cu/Zn SOD, ubiquitin and phosphorylated neurofilament protein (NFP), the intensities of which were much higher in the NHIs than in the surrounding cytoplasm. In control mice, significant Cu/Zn SOD precipitation was not observed to be limited to any particular region of the neuronal cytoplasm. Intracytoplasmic vacuoles in the neuronal soma and processes of Gly93Ala mice were not stained by any of these antibodies. These results indicate that Cu/Zn SOD colocalizes with ubiquitin and phosphorylated NFP in NHIs of mice expressing mutant Cu/Zn SOD; similar findings have been shown for Lewy body-like inclusions of familial ALS patients with Cu/Zn SOD mutation. Moreover, our results point to the possibility that Cu/Zn SOD mutation may have a role in the abnormal Cu/Zn SOD accumulation in the NHIs, in association with motor neuron degeneration.

Animals↗
PubMed1998

Inducible nitric oxide synthase (iNOS)-like immunoreactivity in argyrophilic, tau-positive astrocytes in progressive supranuclear palsy.

The immunoreactivity to the free radical-related enzymes, nitric oxide synthase (NOS) and superoxide dismutase (SOD), was examined in brain tissue in progressive supranuclear palsy (PSP). To determine the relationship between the immunoexpression of these enzymes and tau-positive, argyrophilic cytoplasmic inclusions, which are constantly present in PSP brains, double-label immunohistochemistry was applied. We demonstrated for the first time that strong inducible NOS-like immunoreactivity (iNOS-ir) was detected in tau-positive astrocytes that bore tufts of abnormal fibers (TAF), but not in oligodendrocytes containing argyrophilic/tau-positive coiled bodies nor in microglia. No brain NOS-ir was detected in neurons with neurofibrillary tangles. MnSOD-ir was also detected in tau-positive astrocytes and oligodendrocytes. Nitrotyrosine-ir of variable intensity was observed in astrocytes, oligodendrocytes and neurons. Our results indicate: (1) that TAF-bearing astrocytes may be a major source of excessive NO in PSP brains; (2) that after the induction of iNOS by unknown stimulating factors, TAF-bearing astrocytes produce an excessive amount of NO that exceeds the detoxification capability of SOD; and (3) that peroxynitrite and excessive NO, both cytotoxic, may be present in astrocytes, oligodendrocytes and neurons. Although the precise relationship between NO production and neuronal cell death in PSP remained uncertain, based on the specificity of TAF for PSP brains, our results indicated a possible mechanism of NO-mediated cytotoxicity that may contribute to the neuronal and glial cell damage followed by abnormal tau accumulation in this disease.

Aged↗
PubMed1998

Astrocytic plaques and tufts of abnormal fibers do not coexist in corticobasal degeneration and progressive supranuclear palsy.

Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) are characterized by their unique clinical features and neuronal pathology. Although astrocytic plaques and tufts of abnormal fibers have been suggested to be specific histopathologic markers, recent studies have revealed significant clinicopathologic overlap between CBD and PSP. Based on the distinctive camera lucida profile of astrocytic inclusions on Gallyas-Braak silver staining, we found that astrocytic plaques and tufts of abnormal fibers did not coexist in the same patient among 30 cases of clinically diagnosed CBD, PSP and atypical Parkinson's disease. Using Tau immunohistochemistry it was difficult to verify the absence of tufts of abnormal fibers. A morphometric analysis revealed that the two groups classified by the presence or absence of astrocytic plaques and tufts of abnormal fibers exhibited significant differences in the density of ballooned neurons and neurofibrillary tangles and degeneration of the subcortical nuclei. Assessment using the NINDS neuropathologic criteria revealed that the cases with astrocytic plaques and tufts of abnormal fibers closely correspond to CBD and typical PSP, respectively. In addition, the cases lacking either of these two astrocytic inclusions had atypical PSP according to the NINDS criteria, and were associated with novel tau-positive astrocytes (spiny astrocytes). We thus conclude that astrocytic plaques and tufts of abnormal fibers are highly characteristic structures for CBD and typical PSP, respectively. We emphasize the importance of strict differentiation between different astrocytic inclusions not only for diagnosis, but also for further studies for elucidation of their role in the disease mechanisms of CBD and PSP.

Aged↗
PubMed1998

The expressions of mRNAs for interleukin-6 (IL-6) and the IL-6 receptor (IL-6R) in the rat hypothalamus and midbrain during restraint stress.

Over the past few years, it has been reported that physical and psychological stress elevate plasma interleukin-6 (IL-6), and that neural cells can produce IL-6 and have receptors for IL-6 (IL-6R). However, it is unknown whether IL-6 plays a role in regulating the functions of neural cells in response to stress. We demonstrated recently, using the reverse transcriptase-polymerase chain reaction (RT-PCR), that the levels of mRNAs for IL-6 and IL-6R in the rat brain are changed by restraint stress for four hours. In the present study, we investigated the expression of mRNAs for IL-6 and the IL-6R in the rat hypothalamus and midbrain during restraint stress. After rats had been restrained for 10, 30, 60, 120 or 240 min, the hypothalamus and midbrain were removed immediately and levels of IL-6 mRNA and of IL-6R mRNA in these regions were determined by RT-PCR. The expression of mRNAs for IL-6 and IL-6R in both regions was reduced after short-term (30-60 min) restraint stress and tended to return toward the control level after 120 min restraint stress. After long-term (240 min) restraint stress, the level of IL-6 mRNA was significantly increased in the midbrain, while the level of IL-6R mRNA was significantly reduced in both regions. These findings suggest that the need for IL-6 might decline after short-term restraint stress and, moreover, that the synthesis and secretion of IL-6 might be enhanced and IL-6 might be needed as a neurotrophic factor in the midbrain after long-term stress.

Animals↗
PubMed1998

Cbfa1 in bone development.

A factor fundamental to bone formation has been identified. Gene targeting shows that core-binding factor alpha 1 (Cbfa1) plays an essential role in bone formation and osteoblast differentiation. Thus, it is now possible to begin examining the molecular mechanism of bone formation--especially osteoblast differentiation.

Animals↗
PubMed1998

Molecular analysis of two pre-mutations in myotonic dystrophy.

Here we report two families with myotonic dystrophy (DM) in which the asymptomatic parent proved to be in a pre-mutation state. Polymerase chain reaction (PCR) analysis of the region spanning the CTG expansion demonstrated that one father of the proband possessed (CTG)n repeats of n = 12 and 44 copies and the other of 15 and 47. Clinical examination showed no definite signs of DM in these two men. Haplotype analysis of DNA markers close to the DM protein kinase (DMPK) gene suggested a common ancestral DM mutation. A continuous gradient of repeat sizes from normal to abnormal range can explain this phenomenon.

Adult↗
PubMed1998

Secondary lengthening of the reconstructed mandible using a gradual distraction technique--two case reports.

We have performed mandibular lengthening to restore oral function in 2 cases after tumour resection. Both cases had already undergone a vascularised fibular graft for mandibular reconstruction and had severe contracture and absence of an alveolar ridge for dentures. Gradual distraction was applied after corticotomy of the fibular bone at 0.9 mm per day. After completion of bone lengthening of 20-30 mm, both patients underwent a split thickness skin graft to obtain a good alveolar ridge for dentures and implants. Osteointegrated implants have since been applied in one of these cases, and the other patient has been able to eat a normal diet using dentures. Gradual distraction is applicable for vascularised bone grafts and useful for restoration of the alveolar ridge to accommodate dentures in cases with severe contracture of the oral space after tumour ablation.

Humans↗
PubMed1998

Papillary glioneuronal tumor: a new variant of mixed neuronal-glial neoplasm.

We describe the clinicopathologic features of nine cases of a unique papillary glioneuronal tumor (PGNT) exhibiting astrocytic as well as extensive and varied neuronal differentiation. The four male and five female patients studied ranged in age from 11 to 52 years (mean 27.7 years). They either presented with mild neurologic symptoms or were asymptomatic. Magnetic resonance imaging showed demarcated cystic, 1.5-cm to 7-cm contrast-enhancing masses; five involved the temporal lobe, two the parietal, and two the frontal. All but one were totally resected. No recurrence was noted despite a follow-up period of 3 years. Two microscopic components were evident: 1) compact pseudopapillae composed of hyalinized vessels covered by a single layer of glial fibrillary acid protein (GFAP)-positive astrocytes and 2) synaptophysin-positive neuronal cells of varying size, including neurocytes, ganglioid cells, and ganglion cells within neuropil. Immunostains for chromogranin-A were negative, as was in situ hybridization for chromogranin-A mRNA. Ultrastructurally, neuronal cells featured microtubule-containing processes and aberrant synaptic terminals, but dense core granules were rare. Overall, cellularity was moderate and atypia was minimal. No mitotic activity or necrosis was noted. The proportions of the two components varied, but essential morphologic findings were identical in all cases. In that the clinical, radiographic, and morphologic characteristics of PGNT are distinctive, it appears to represent a previously undescribed form of mixed neuronal-glial tumor of the central nervous system.

Adolescent↗
PubMed1998

Treatment of maxillary molars with vertical fractures.

To date, there has been no reliable method for treating bucco-palatal fractured maxillary molar teeth. We have developed a simple repositioning method to fix teeth fractured in this way using wire. The effectiveness of this new approach was evaluated in both in vitro experimental research and clinical studies.

Calcium Hydroxide↗
PubMed1998

Effects of repeated clarithromycin administration on the pharmacokinetic properties of pindolol in rats.

The goal of the present work was to determine the effect of clarithromycin (CAM) administration on the pharmacokinetic properties of pindolol in rats. The binding of pindolol to serum components increases proportionally with increasing alpha1-acid glycoprotein (AGP) concentration, indicating that AGP might play a major role in the binding of pindolol. After intravenous administration of pindolol to rats, the CAM-treated group showed a decrease in the volume of distribution, an increase in AUC and no change in the half-life as compared to the control group. Treatment with CAM increased the AGP concentration only. The serum concentration of albumin and creatinine, as well as the metabolic activity of hepatic microsomes towards pindolol, were not altered. Good correlation was observed between the AUC of pindolol in rats and the AGP concentration in serum. Moreover, at 5 min after the administration of an intravenous bolus dose of pindolol to CAM-treated rats, the free concentration of pindolol was lower but the total concentration was higher, compared with the control rats. These results suggested that the influence of CAM on the pharmacokinetic properties of pindolol in CAM-treated rats can be explained by protein binding which, in turn, may be associated with variations in AGP concentration.

Adrenergic beta-Antagonists↗
PubMed1998

[Clinical usefulness of scatter and attenuation correction for brain single photon emission computed tomography (SPECT) in pediatrics].

This investigation was undertaken to study clinical usefulness of scatter and attenuation correction (SAC) of brain SPECT in infants to compare the standard reconstruction (STD). The brain SPECT was performed in 31 patients with 19 epilepsy, 5 cerebro-vascular disease, 2 brain tumor, 3 meningitis, 1 hydrocephalus and psychosis (mean age 5.0 +/- 4.9 years old). Many patients was necessary to be injected sedatives for restraining body motion after Technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) was injected at the convulsion or rest. Brain SPECT data were acquired with triple detector gamma camera (GCA-9300 Toshiba Japan). These data were reconstructed by filtered backprojection after the raw data were corrected by triple energy windows method of scatter correction and Chang filtered method of attenuation correction. The same data was reconstructed by filtered backprojection without these corrections. Both SAC and STD SPECT images were analyzed by the visual interpretation. The uptake ratio of cerebral basal nuclei was calculated by the counts of the thalamus or lenticular nuclei divided by the cortex. All images of SAC method were excellent than that of STD method. The thalamic uptake ratio in SAC method was higher than that of STD method (1.22 +/- 0.09 > 0.87 +/- 0.22 p < 0.01). The lenticular nuclear uptake ratio in SAC method was higher than that of STD method (1.26 +/- 0.15 > 1.02 +/- 0.16 p < 0.01). Transmission scan is the most suitable method of absorption correction. But the transmission scan is not adequate for examination of children, because this scan needs a lot of time and the infants are exposed by the line source radioisotope. It was concluded that these scatter and absorption corrections were most suitable method for brain SPECT in pediatrics.

Adolescent↗
PubMed1998

[CBFA1/PEBP2 alpha A].

A transcription factor, Cbfa1/Pebp2 alpha A, which belongs to runt-domain gene family, is preferentially expressed in the osteoblast lineage. Cbfa1/Pebp2 alpha A-deficient mice lacked both intramembranous and endochondral ossification completely. The differentiation of osteoblast was blocked, and the maturational disturbance of osteoclasts was also observed in the mutant mice. Further, the Cbfa1/Pebp2 alpha A expression in nonosteoblastic cells induced osteoblastic markers in vitro. These data demonstrate that Cbfa1 is an essential transcription factor for osteoblast differentiation and bone formation. Heterozygously mutated mice in the Cbfa1/Pebp2 alpha A locus showed the similar phenotype with cleidocranial dysplasia, which is an autosomal inherited disease. And the mutations of CBFA1/PEBP2 alpha A locus were identified in the patients with cleidocranial dysplasia.

Animals↗