Search PubMed⌕ Search

Biomedical subjects

T Komori

Publications and source records attributed to T Komori.

At least 73 records · Page 4Linked to original sources
PubMed2001

[Osteoblast differentiation and a transcriptional factor, Cbfa1].

Cbfa1 is a member of runt-domain gene family. Cbfa1-deficient mice lack of bone formation and introduction of Cbfa1 into non-osteoblastic cells induced the expression of osteoblast specific genes. Cbfa1-deficient calvarial cells were composed of immature mesenchymal cells and can differentiated into adipocytes and chondrocytes. Based on these findings, Cbfa1 has been identified as a master regulatory gene of the osteoblast differentiation and it has been suggested that Cbfa1 plays an essential role in determining the lineage of multipotential mesenchymal precursor cells.

English Abstract↗
PubMed2000

A fundamental transcription factor for bone and cartilage.

Cbfa1-deficient mice were found to show a complete lack of bone formation owing to the maturational arrest of osteoblasts. Cbfa1 plays key roles in the determination of osteoblastic lineage from multipotential mesenchymal cells, their differentiation into mature osteoblasts, and transcriptional regulation of bone matrix-related genes. Cbfa1 positively regulates chondrocyte maturation and osteoclast differentiation and is required for vascular invasion into cartilage. Therefore, complete elucidation of the function of Cbfa1 and its signaling would be of great benefit in understanding skeletogenesis.

Animals↗
PubMed2000

Enhanced motor cortical excitability in the unaffected hemisphere after hemispherectomy.

We evaluated motor cortical excitability of the unaffected hemisphere in three patients with intractable epilepsy who underwent hemispherectomy, using transcranial magnetic stimulation (TMS) and PET. TMS of the unaffected hemisphere evoked motor responses not only in the contralateral muscles but also in the ipsilateral ones in all the patients. A PET study in one patient showed activation of the unaffected motor cortex by movement of either arm. All of these responses were enhanced after the hemispherectomy, probably due to motor cortical disinhibition by transection of the corpus callosum. The PET study also showed postoperative activation of the premotor area of the unaffected hemisphere. These phenomena indicate posthemispherectomy neuroplastic reorganization leading to preservation of the motor function after the operation.

Adult↗
PubMed2000

iNOS and nitrotyrosine immunoreactivity in amyotrophic lateral sclerosis.

We carried out an immunohistochemical investigation of the spinal cords of 15 patients with sporadic amyotrophic lateral sclerosis (ALS), using antibodies to inducible nitric oxide synthase (iNOS) and nitrotyrosine; our purpose was to search for a possible role of increased oxidative damage in the motor system that may contribute to the neurodegenerative process in this disease. Specimens from 16 patients without any neurological disease served as controls. In the controls, normal-appearing neurons and their dendrites were negatively immunostained for iNOS. In the ALS patients, most of normal-appearing anterior horn neurons did not show iNOS immunoreactivity either in the perikarya or in their dendrites. However, many of the degenerated neurons showing central chromatolysis or simple atrophy demonstrated focally or diffusely positive iNOS immunoreactivity within the perikarya and their neuronal processes. In the neuropil of the anterior horns, the reactive astrocytes were more intensely immunostained for iNOS as compared with the controls. Some of the swollen proximal axons (spheroids) were focally or diffusely immunostained by the antibody. The corticospinal tracts demonstrated positive iNOS immunoreactivity of proliferated reactive astrocytes. The immunostaining pattern of nitrotyrosine in the anterior horn neurons of the spinal cord was similar to that of iNOS. These findings suggest that selective nitric oxide-mediated oxidative damage in the motor system plays a part in the pathomechanism of the neuronal degeneration in the spinal cord of sporadic ALS.

Adult↗
PubMed2000

Multilineage differentiation of Cbfa1-deficient calvarial cells in vitro.

We characterized calvaria-derived cells of Cbfa1-deficient mice to determine their stages of differentiation. In long-term culture, Cbfa1-deficient calvarial cells did not acquire osteoblastic phenotypes, but numerous adipocyte foci appeared with an increase in the expression of marker genes for adipocyte differentiation. In culture with BMP-2, Cbfa1-deficient calvarial cells still failed to generate bone nodules but differentiated into chondrocytes and further to terminal hypertrophic chondrocytes, and adipocyte foci were decreased. Cbfa1-deficient calvarial cells transplanted into the peritoneal cavity of athymic mice using BMP-2-coated diffusion chambers generated cartilage but not bone. These data indicate that Cbfa1-deficient calvarial cells completely lack the ability to differentiate into mature osteoblasts and Cbfa1 has an inhibitory function in adipocyte differentiation. As Cbfa1-deficient calvarial cells were enriched with immature mesenchymal cells, which can differentiate into adipocytes and chondrocytes, it is suggested that Cbfa1 plays an essential role in determining the lineage of multipotential mesenchymal precursor cells.

Adipocytes↗
PubMed2000

Loss of the muscle silent period evoked by transcranial magnetic stimulation of the motor cortex in patients with cervical cord lesions.

The silent period following motor evoked potentials in small hand muscles after transcranial magnetic stimulation (TMS) of the human motor cortex is considered to be cortical origin. The authors report three patients with cervical spinal cord lesions who showed loss of the cortical silent period (CSP) after TMS. One patient had traumatic cervical cord injury, and the other two patients had cervical spondylosis. All the patients had cervical cord compression on magnetic resonance imaging. TMS study showed loss of the CSP in both the hand and foot muscles in two patients and only in the foot muscle in one patient. Paired TMS study in one patient with pseudoathetotic hands showed reduced inhibition within the motor cortex. The hand weakness or interrupted sensory afferents might have caused motor cortical reorganization or hyperexcitability, leading to the loss of the CSP.

Adult↗
PubMed2000

Differential expression of plastidic aldolase genes in Nicotiana plants under salt stress.

Two homologous genes of plastidic fructose-1,6-bisphosphate aldolase (AldP) isozymes were isolated from green leaves of a salt stress-tolerant Nicotiana species, Nicotiana paniculata, by differential screening. The products of the corresponding genes, NpAldP1 and NpAldP2, were 91% identical to each other and 70-85% identical to the other known plant plastidic aldolases. Although these two genes showed similar organ-specific expression and daily cycles, their responses to salt stress differed: mRNA accumulation of NpAldP2 increased, but that of NpAldP1 slightly decreased. The mRNA accumulations of their counterparts of two other Nicotiana species, NeAldP1 and NeAldP2 (Nicotiana excelsior), and NaAldP1 and NaAldP2 (Nicotiana arentsii) were studied under the same stress condition. N. arentsii conserved accumulation profiles similar to N. paniculata, but N. excelsior did not. In N. excelsior, accumulation of NeAldP1 decreased to 50% of the control after stress and gradually recovered thereafter, whereas accumulation of NeAldP2 temporarily decreased and reached 250% of the control by the third day of stress. Southern blot analysis indicated that NpAldP1, NpAldP2, NaAldP1, and NaAldP2 include one or two closely related genes and NeAldP1 and NeAldP2 several.

Journal Article↗
PubMed2000

Autonomic failure in ALS with a novel SOD1 gene mutation.

The authors report a patient with ALS and a novel SOD1 gene mutation who was in the totally locked-in state and developed autonomic failure followed by sudden cardiac arrest. A neuropathologic study showed widespread multisystem degeneration, including involvement of the autonomic nuclei in the medulla and spinal cord. SOD1 gene analysis detected a missense mutation of V118L in exon 4. These findings show notable phenotypic heterogeneity for SOD1-associated ALS.

Adult↗
PubMed2000

Cbfa1 is a positive regulatory factor in chondrocyte maturation.

Cbfa1 is a transcription factor that belongs to the runt domain gene family. Cbfa1-deficient mice showed a complete lack of bone formation due to the maturational arrest of osteoblasts, demonstrating that Cbfa1 is an essential factor for osteoblast differentiation. Further, chondrocyte maturation was severely disturbed in Cbfa1-deficient mice. In this study, we examined the possibility that Cbfa1 is also involved in the regulation of chondrocyte differentiation. mRNAs for both Cbfa1 isotypes, type I Cbfa1 (Pebp2alphaA/Cbfa1) and type II Cbfa1 (Osf2/Cbfa1 or til-1), which are different in N-terminal domain, were expressed in terminal hypertrophic chondrocytes as well as osteoblasts. In addition, mRNA for type I Cbfa1 was expressed in other hypertrophic chondrocytes and prehypertrophic chondropcytes. In a chondrogenic cell line, ATDC5, the expression of type I Cbfa1 was elevated prior to differentiation to the hypertrophic phenotype, which is characterized by type X collagen expression. Treatment with antisense oligonucleotides for type I Cbfa1 severely reduced type X collagen expression in ATDC5 cells. Retrovirally forced expression of either type I or type II Cbfa1 in chick immature chondrocytes induced type X collagen and MMP13 expression, alkaline phosphatase activity, and extensive cartilage-matrix mineralization. These results indicate that Cbfa1 is an important regulatory factor in chondrocyte maturation.

Animals↗
PubMed2000

Aldose reductase inhibition prevents glucose-induced apoptosis in cultured bovine retinal microvascular pericytes.

The pathogenesis of pericyte loss, an initial deficit in the early stage of diabetic retinopathy, remains unclear. Polyol pathway hyperactivity has been implicated in the pathogenesis of diabetic retinopathy, and recent studies have suggested that apoptosis may be involved in pericyte loss. The present study was conducted to investigate whether high glucose induces apoptosis in cultured bovine retinal pericytes. The effect of an aldose reductase inhibitor, SNK-860, was also examined. After a 5 day incubation with various concentrations of glucose (5.5-40 m M) in the presence or absence of SNK-860, the cell viability and the percentages of dead cells were measured, and staining with the TUNEL method and Hoechst 33342, and DNA electrophoresis were performed. High glucose reduced the viability and increased the percentages of dead cells. TUNEL-positive cells were observed in pericytes under high glucose, but not in those under 5.5 m M glucose. In the staining of nuclei with Hoechst 33342, the percentage of apoptotic cells in total cells counted under high glucose was higher than that under 5.5 m M glucose. DNA electrophoresis of pericytes cultured with high glucose demonstrated a 'ladder pattern'. Hyperosmolarity also induced apoptosis in pericytes, but less than that by high glucose. SNK-860 inhibited the glucose-induced apoptosis in pericytes. These observations suggest that the pericyte loss in diabetic retinopathy involves an apoptotic process, and that the polyol pathway hyperactivity plays an important role in inducing apoptosis in pericytes by high glucose.

Aldehyde Reductase↗
PubMed2000

Serial changes in N-isopropyl-p[125I]-iodoamphetamine in mouse lung observed with a confocal laser scanning microscope.

Serial changes in N-isopropyl-p[125I]-iodoamphetamine (125I-IMP) in mouse lungs were observed with a confocal laser scanning microscope. Male mice were intravenously injected with 125I-IMP and subjected to autoradiographic procedures 20 minutes, and 3 and 24 hours after injection. Differential interference contrast (DIC) images and confocal images were obtained with a confocal laser scanning microscope, and superimposed images were evaluated. Large numbers of silver grains were observed in the interstitium, bronchioles, and alveolar sacs 20 minutes after the injection, and lamellar distribution of the grains was observed on the ciliary surface. The numbers of silver grains in the interstitium and bronchioles had decreased 3 hours after the injection of 125I-IMP, but the numbers of silver grains in the alveolar spaces had not. Although small numbers of silver grains remained in both the bronchioles and alveolar sacs 24 hours after the injection, most of them had washed out. Confocal laser scanning microscopy is considered to be a useful procedure for studying the distribution of radioisotopes by microautoradiography, because it allows clear autoradiographs to be obtained in which tissues and silver grains are perfectly matched and all silver grains are in focus.

Animals↗
PubMed2000

Technetium-99m MIBI single photon emission computed tomography as an indicator of prognosis for patients with lung cancer-preliminaly report.

PURPOSE: We performed technetium-99m hexakis-2-methoxyisobutylisonitrile (Tc-99m MIBI) single photon emission computed tomography (SPECT) in 23 patients with primary lung cancer between July 1993 and March 1996. We evaluated the relationships among the uptake ratio, retention index and the prognosis after radiation therapy and/or chemotherapy. MATERIALS AND METHODS: Tc-99m MIBI SPECT was performed at 30 minutes and at 3 hours after intravenous injection of 600 MBq of Tc-99m MIBI with three gamma camera detectors (GCA-9300A/HG) on transverse SPECT images. Regions of interest were set in the area of abnormal uptake of Tc-99m MIBI and in the contralateral normal lung. The ratio of uptake in the lesion to that in the contralateral normal lung was obtained on early images (early ratio; ER) as well as delayed images (delayed ratio: DR). The retention index (RI) was calculated as follows: RI = (DR - ER)/ER x 100. The ratio was compared with survival time and prognostic factors. RESULTS: There was no correlation between ER and DR. The patients with high RI survived longer than those with low RI (median survival, 19.4 months vs. 9.4 months; p = 0.0104 by the Mantel-Cox test). CONCLUSION: These results suggest that RI is the most useful among Tc-99m MIBI indices of primary lung cancer in predicting prognosis.

Adult↗
PubMed2000

Excitatory amino acid transporter 1 and 2 immunoreactivity in the spinal cord in amyotrophic lateral sclerosis.

The spinal cord of 20 patients with amyotrophic lateral sclerosis (ALS) and 5 patients with lower motor neuron disease (LMND) were investigated immunohistochemically using anti-human excitatory amino acid transporter 1 (EAAT1) and EAAT2 antibodies which are the astrocytic transporters. The purpose of the study was to examine relationships between EAAT1 and EAAT2 immunoreactivity and degeneration of anterior horn neurons. Specimens from 20 patients without any neurological disease served as controls. In controls, spinal cord gray matter was densely immunostained by antibodies, whereas the white matter was generally not immunostained. In motor neuron disease (MND) patients, EAAT1 immunoreactivity was relatively well preserved in the gray matter despite neuronal loss of anterior horn cells. On the other hand, EAAT2 immunoreactivity in anterior horns correlated with the degree of neuronal loss of anterior horn cells: in the patients with mild neuronal depletion, anterior horns were densely immunostained by the antibody, whereas in the patients with severe neuronal loss, EAAT2 expression was markedly reduced. Degenerated anterior horn cells frequently showed a much denser EAAT1 and EAAT2 immunoreactivity around the surface of the neurons and their neuronal processes than that observed in normal-appearing neurons. There was no difference in the expression of EAAT1 and EAAT2 immunoreactivity between LMND and ALS patients. These findings suggest that in the early stage of degeneration of anterior horn cells, EAAT1 and EAAT2 immunoreactivity is preserved in the astrocytic foot directly attached to normal-appearing neurons, whereas levels of EAAT1 and EAAT2 protein rather increase in the astrocytic foot directly attached to degenerated anterior horn neurons; the latter effect most probably reduces the elevated glutamate level, compensates for the reduced function of astroglial glutamate transporters, or represents a condensation of EAAT1 and EAAT2 immunoreactivity secondary to loss of neurites and greater condensation of astrocytic processes. Thus, we demonstrate a difference in EAAT1 and EAAT2 immunoreactivity in different stages of progression in ALS, as a feature of the pathomechanism of this disease.

ATP-Binding Cassette Transporters↗
PubMed2000

Effects of repeated stress on expression of interleukin-6 (IL-6) and IL-6 receptor mRNAs in rat hypothalamus and midbrain.

We examined the effects of single and repeated stress on the expression of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) mRNAs in the rat midbrain and hypothalamus using reverse transcriptase-polymerase chain reaction (RT-PCR). Following a single episode of restraint stress for 4 hours (1R) or 4 hours per day on two (2R) or three (3R) consecutive days, the hypothalamus and midbrain were removed immediately and the levels of IL-6 and IL-6R mRNAs in both regions were determined. Regional differences in stress-related changes in mRNA levels were noted. The expression of IL-6 mRNA in the hypothalamus did not change in 1R group but decreased in 2R and 3R groups. The expression of IL-6R mRNA in the same region significantly diminished in all groups. In the midbrain, the expression of IL-6 mRNA increased in 1R group and decreased in 2R and 3R, while the expression of IL-6R mRNA significantly diminished in 1R and 3R groups but was not different from control in 2R group. Our findings indicate that repeated stress in rats produce changes in IL-6 and IL-6R mRNAs in the midbrain and hypothalamus that are different than those of a single stress episode.

Animals↗
PubMed2000

Forced expression of terminal deoxynucleotidyl transferase in fetal thymus resulted in a decrease in gammadelta T cells and random dissemination of Vgamma3Vdelta1 T cells in skin of newborn but not adult mice.

The repertoire of lymphocyte receptor genes encoded in a germline is further diversified by a number of processes, including the template-independent addition of nucleotides (N regions) by means of terminal deoxynucleotidyl transferase (TdT). Normally, mouse gammadelta T cells in the early fetal thymus, whose T-cell receptor (TCR) genes lack N regions and are encoded by Vgamma3-Jgamma1 and Vdelta1-Ddelta2-Jdelta2 with canonical junctions (invariant Vgamma3Vdelta1), are thought to be the precursors of dendritic epidermal T cells (DETC). We generated mutant mice whose endogenous TdT promoter was replaced with the lck promoter through homologous recombination. These mutant mice expressed TdT in fetal thymus, had abundant N regions and infrequent canonical junctions in gamma and delta rearrangements, and showed a decreased number of gammadelta T cells. Various Vgamma3Vdelta1 T cells, most of which had N regions in their TCR genes, were found to disseminate in the skin of newborn mutant mice, whereas normal numbers of DETCs with the invariant Vgamma3Vdelta1 rearrangement were observed in adult mutants. These data demonstrate that the regulation of TdT expression during fetal development is important for the generation of gammadelta T cells, and that Vgamma3Vdelta1 T cells, which have various junctional sequences in their TCR genes, randomly disseminate in skin, but invariant Vgamma3Vdelta1 T cells have a great advantage for proliferation in skin.

Animals↗
PubMed2000

Eicosapentaenoic acid stimulates nitric oxide production and decreases cardiac noradrenaline in diabetic rats.

1. The aim of the present study was to investigate whether long-term oral administration of eicosapentaenoic acid increases nitric oxide (NO) production and affects cardiac sympathetic activity in rats with diabetes mellitus. 2. We measured changes in urinary excretion of NO3-, a stable NO metabolite, and cardiac noradrenaline (NA) concentrations in non-diabetic rats and streptozotocin-induced diabetic rats treated with either ethyl icosapentate (EPA-E; 100 mg/kg per day; n = 10), a purified ethyl esterification product of eicosapentaenoic acid, or vehicle (distilled water; n = 10) for 6 weeks. The effects of N(G)-nitro-L-arginine (L-NNA), a NO synthase inhibitor, on urinary NO3- excretion and cardiac NA concentrations were also investigated in diabetic rats treated with EPA-E. 3. Urinary NO3- excretion was higher at weeks 5 and 6 in diabetic rats treated with EPA-E than in diabetic rats treated with vehicle (week 5: 120+/-8 vs 51+/-11 micromol/g per day, respectively (P<0.01); week 6: 279+/-83 vs 73+/-9 micromol/g per day, respectively (P<0.01)). Cardiac NA concentrations were higher in diabetic rats than in non-diabetic rats and were decreased in the left atrium and both ventricles in diabetic rats treated with EPA-E compared with control. Systemic administration of L-NNA abolished the increase in urinary excretion of NO3- and the decrease in cardiac NA concentrations in diabetic rats treated with EPA-E. 4. Long-term oral administration of EPA-E may stimulate NO production and increased NO is likely to play a role in inhibiting enhanced cardiac sympathetic activity in diabetic rats.

Animals↗