Biomedical subjects

H Mitani

Publications and source records attributed to H Mitani.

At least 19 recordsLinked to original sources

PubMed2006

Local RANKL gene transfer to the periodontal tissue accelerates orthodontic tooth movement.

It has been reported that not only selective alveolar-bone resorption, but also receptor activator of nuclear factor kappa B ligand (RANKL) expression is induced on the compressed side of an orthodontically moving tooth. Numerous reports have described the pharmacological acceleration of tooth movement (TM) through the activation of osteoclasts. However, because of rapid flush out by blood circulation, daily systemic administration or daily local injection is needed. Previously, we discovered that every-3-days OPG gene transfer to the periodontal-tissue inhibited RANKL-mediated osteoclastogenesis and diminished experimental TM. Therefore, we hypothesized that local RANKL gene transfer into the periodontal tissue would accelerate TM. The upper first molars of 6-week-old male Wistar rats were moved palatally using fixed orthodontic wires. The inactivated hemagglutinating-virus of Japan (HVJ) envelope vector containing the mouse RANKL expression plasmid was injected periodically into the palatal periodontal tissue of the upper first molars during TM. Local RANKL gene transfer significantly enhanced RANKL expression and osteoclastogenesis in periodontal tissue without any systemic effects. The TM rate was significantly increased in the RANKL gene transfer side. In conclusion, we demonstrated that transfer of the RANKL gene to the periodontal-tissue activated osteoclastogenesis and accelerated the amount of experimental TM. Local RANKL gene transfer might be a useful tool not only for shortening orthodontic treatment, but also for moving ankylosed teeth where teeth, fuse to the surrounding bone.

Animals↗

PubMed2006

Compressive force induces osteoblast apoptosis via caspase-8.

Periodontal remodeling during orthodontic tooth movement is a result of mechanical stresses. The application of excessive orthodontic force induces cell death. However, the nature of compressive force-induced cell death is unclear. We examined whether the in vitro application of continuous compressive force would induce apoptosis in human osteoblast-like cells (MG-63 cells), and investigated the mechanism by which apoptosis was initiated. The cells became aligned irregularly, and cell viability decreased, indicating that the compressive force caused cell death. According to the TUNEL analysis, the number of apoptotic cells increased significantly in a time-and force-dependent manner. Caspase-3 activity increased with the magnitude of the compressive force, and this effect was reduced significantly by a caspase-8 inhibitor, whereas a caspase-9 inhibitor had no such effect. We conclude that the in vitro application of compressive force can induce apoptosis in MG-63 cells through the activation of caspase-3 via the caspase-8 signaling cascade.

Analysis of Variance↗

PubMed2006

Cyclical tensile force on periodontal ligament cells inhibits osteoclastogenesis through OPG induction.

The periodontal ligament (PDL) maintains homeostasis of periodontal tissue under mechanical tensile-loading caused by mastication. Occlusal load inhibits atrophic alveolar bone resorption. Previously, we discovered that continuous compressive force on PDL cells induced osteoclastogenesis-supporting activity, with up-regulation of RANKL. We hypothesized that, unlike compression, cyclical tensile force up-regulates OPG expression in PDL cells via TGF-beta up-regulation, and does not induce osteoclastogenesis-supporting activity. PDL cells were mechanically stimulated by cyclical tensile force in vitro. The conditioned media of PDL cells that had been subjected to cyclical tensile force inhibited osteoclastogenesis. Cyclical tensile force up-regulated not only RANKL mRNA expression, but also OPG mRNA expression in PDL cells. Tensile force up-regulated TGF-beta expression in PDL cells as well. Administration of neutralizing antibodies to TGF-beta inhibited OPG up-regulation under cyclical tensile-force stimulation in a dose-dependent manner. Additionally, the osteoclastogenesis-inhibitory effect of the conditioned media of PDL cells under cyclical tensile force was partially rescued by the administration of TGF-beta neutralizing antibodies. In conclusion, tensile force inhibited the osteoclastogenesis-supporting activity of PDL cells by inducing the up-regulation of OPG via TGF-beta stimulation.

Adult↗

PubMed2006

Clodronate inhibits PGE(2) production in compressed periodontal ligament cells.

Periodontal ligament (PDL) cells play an essential role in orthodontic tooth movement. We recently reported that clodronate, a non-N-containing bisphosphonate, strongly inhibited tooth movement in rats, and thus could be a useful adjunct for orthodontic treatment. However, it is not clear how clodronate affects the responses of PDL cells to orthodontic force. In this study, we hypothesized that clodronate prevents the mechanical stress-induced production of prostaglandin E(2) (PGE(2)), interleukin-1beta (IL-1beta), and nitric oxide (NO) in human PDL cells. A compressive stimulus caused a striking increase in PGE(2) production, while the responses of IL-1beta and NO were less marked. Clodronate concentration-dependently inhibited the stress-induced production of PGE(2). Clodronate also strongly inhibited stress-induced gene expression for COX-2 and RANKL. These results suggest that the inhibitory effects of clodronate on tooth movement and osteoclasts may be due, at least in part, to the inhibition of COX-2-dependent PGE(2) production and RANKL expression in PDL cells.

Adult↗

PubMed2005

Osteoclastogenic activity during mandibular distraction osteogenesis.

Mandibular distraction osteogenesis is a well-developed clinical modality for the treatment of craniofacial deformities and dental arch discrepancies, in combination with orthodontic treatment. However, in our previous study, orthodontic tooth movement into the distraction gap caused severe root resorption. The present study aimed to clarify the osteoclastogenic activity of cells in the distraction gap. We hypothesized that the gene expression of osteoclastogenic- and osteoclast-supporting molecules in osteoblasts and stromal cells would increase at distraction sites during the consolidation period. An animal model experiment involving rabbits was designed for mandibular distraction osteogenesis and subjected to in situ hybridization analysis. The number of osteoclasts was larger in the distraction gap during the early consolidation period than in normal controls, due to an increase of gene expression for osteoclastogenic cytokines in osteoblasts. It was concluded that osteoclastogenic and osteoclastic activities are stimulated at distraction sites during the early consolidation period.

Animals↗

PubMed2005

[Successful removal of an intrapulmonary aberrant needle under video-assisted thoracoscopic surgery; report of a case].

Intrapulmonary aberrant needles are rare in clinical practice. We report the successful removal of intrapulmonary aberrant needle. A 59-year-old man, though he was asymptomatic, was referred to our department after an abnormal shadow had been detected on a chest X-ray. Chest X-ray and chest computed tomography (CT) showed a foreign body suspected to be a metal artifact in the left upper lobe. It was diagnosed as an intrapulmonary aberrant needle and an operation under video-assisted thoracoscopic surgery was performed. Using perioperative fluoroscopy, we could confirm the location of the needle and remove it successfully. An intrapulmonary aberrant needle should be removed surgically, even if the patient is asymptomatic, due to the development of lung abscess or pyothorax and the risk containing harmful matter to health.

Foreign Bodies↗

PubMed2004

Large-scale isolation of ESTs from medaka embryos and its application to medaka developmental genetics.

The medaka is becoming an attractive model organism for the study of vertebrate early development and organogenesis and large-scale mutagenesis projects that are aimed at creating developmentally defective mutants are now being conducted by several groups in Japan. To strengthen the study of medaka developmental genetics, we have conducted a large-scale isolation of ESTs from medaka embryos and developed tools that facilitate mutant analysis. In this study, we have characterized a total of 132,082 sequences from both ends of cloned insert cDNAs from libraries generated at different stages of medaka embryo development. Clustering analysis with 3-prime sequences finally identified a total of 12,429 clusters. As a pilot analysis, 924 clusters were subjected to in situ hybridization to determine the spatial localization of their transcripts. Using EST sequence data generated in the present study, a 60-mer oligonucleotide microarray with 8,091 unigenes (Medaka Microarray 8K) was constructed and tested for its usefulness in expression profiling. Furthermore, we have developed a rapid and reliable mutant mapping system using a set of mapped EST markers (M-marker 2003) that covers the entire medaka genome. These resources will accelerate medaka mutant analyses and make an important contribution to the medaka genome project.

Animals↗

PubMed2004

The mitochondrial genomes of soft ticks have an arrangement of genes that has remained unchanged for over 400 million years.

There are two major groups of ticks: soft ticks and hard ticks. The hard ticks comprise the prostriate ticks and the metastriate ticks. The mitochondrial (mt) genomes of one species of prostriate tick and two species of metastriate ticks had been sequenced prior to our study. The prostriate tick has the ancestral arrangement of mt genes of arthropods, whereas the two metastriate ticks have rearrangements of eight genes and duplicate control regions. However, the arrangement of genes in the mt genomes of soft ticks had not been studied. We sequenced the mt genomes of two species of soft ticks, Carios capensis and Ornithodoros moubata, and a metastriate tick, Haemaphysalis flava. We found that the soft ticks have the ancestral arrangement of mt genes of arthropods, whereas the metastriate tick, H. flava, shares the rearrangements of mt genes and duplicate control regions with the other two metastriate ticks that have previously been studied. Our study indicates that gene rearrangements and duplicate control regions in mt genomes occurred once in the most recent common ancestor of metastriate ticks, whereas the ancestral arrangement of arthropods has remained unchanged for over 400 million years in the lineages leading to the soft ticks and the prostriate ticks.

Animals↗

PubMed2004

Local OPG gene transfer to periodontal tissue inhibits orthodontic tooth movement.

Previously, we discovered that RANKL expression is induced in compressed periodontal ligament cells, and that this promotes osteoclastogenesis on the compression side in orthodontic tooth movement. We hypothesized that local OPG gene transfer to the periodontium would neutralize the RANKL activity induced by mechanical compressive force, thereby inhibiting osteoclastogenesis and diminishing tooth movement. The upper first molars of six-week-old male Wistar rats were moved palatally by means of a fixed-orthodontic wire. A mouse OPG expression plasmid [pcDNA3.1(+)-mOPG] was constructed, and the production of functional OPG protein was confirmed in vitro. The inactivated HVJ envelope vector containing pcDNA3.1(+)-mOPG or PBS was injected periodically into the palatal periodontal tissue of upper first molars. When this local OPG gene transfer was performed, OPG production was induced, and osteoclastogenesis was inhibited. Local OPG gene transfer significantly diminished tooth movement. In this study, we report that OPG gene transfer to periodontal tissue inhibited RANKL-mediated osteoclastogenesis and inhibited experimental tooth movement.

Animals↗

PubMed2004

Repressive effects of yeast extract on photoreactivation of Escherichia coli.

Photoreactivation of Escherichia coli K12 (IFO 3301), in the presence or absence of yeast extract (YE), was investigated after inactivation by low-pressure UV lamp. An endonuclease sensitive site (ESS) assay was used to determine the UV-induced pyrimidine dimers in the genome of E. coli, while a colony-forming ability (CFA) test was also used to examine the survival ratio of E. coli. The YE solution reduced the CFA recovery at a final concentration of 125 mg/L. A dialysis of the YE solution indicated that the YE fraction (with nominal molecular weight >1,000 and <3,500) was effective at repressing the CFA recovery. Interestingly, the repair of ESS was equivalent regardless of the presence of the YE dialysate, while the CFA recovery was significantly repressed in the presence of YE. It was, therefore, suggested that YE components, probably with molecular weights of 1,000-3,500, were effective at repressing the CFA recovery of E. coli without affecting the ESS repair during photoreactivation.

Colony Count, Microbial↗

PubMed2003

Expression of MMP-8 and MMP-13 genes in the periodontal ligament during tooth movement in rats.

Periodontal ligament tissue is remodeled on both the tension and compression sides of moving teeth during orthodontic tooth movement. The present study was designed to clarify the hypothesis that the expression of MMP-8 and MMP-13 mRNA is promoted during the remodeling of periodontal ligament tissue in orthodontic tooth movement. We used the in situ hybridization method and semi-quantitative reverse-transcription/polymerase chain-reaction analysis to elucidate the gene expression of MMP-8 and MMP-13 mRNA. Expression of MMP-8 and MMP-13 mRNA transiently increased on both the compression and tension sides during active tooth movement in vivo. The gene expression of MMP-8 and MMP-13 was induced by tension, while compression indirectly promoted the gene expression of MMP-8 and MMP-13 through soluble factors in vitro. Thus, we concluded that the expression of MMP-8 and MMP-13 is differentially regulated by tension and compression, and plays an important role in the remodeling of the periodontal ligament.

Animals↗

PubMed2002

Estrous-cycle-dependent variation in orthodontic tooth movement.

Sex hormones, including estradiol, play important physiological roles in bone metabolism. The purpose of this study was to investigate whether there is estrous-cycle-dependent variation in orthodontic tooth movement, and, if so, to determine the mechanism. Ten-week-old female Wistar rats were used. They received repeated orthodontic force during specific phases in the estrous cycle. Tooth movement in animals that received force principally in estrus was about 33% greater than that in animals that received such force principally in pro-estrus (p < 0.05). Serum estradiol levels also varied according to the estrous cycle, with a peak during pro-estrus and a nadir during estrus, and were inversely related to tooth movement. Furthermore, there were negative correlations between estradiol and both serum TRAP activity and pyridinoline (r = -0.42, p < 0.05; r = -0.59, p < 0.001). These results suggest that cyclic changes in the estradiol level may be associated with the estrous-cycle-dependent variation in tooth movement through its effects on bone resorption.

Acid Phosphatase↗

PubMed2002

Diurnal variation in the response of the mandible to orthopedic force.

Bone and cartilage metabolism is known to be more active during rest than during periods of activity. The purpose of this study was to examine the hypothesis that mandibular retractive force could be more effective when applied to rats during rest. Mandibular retractive force caused a considerable reduction in the condylar length in experimental groups, and the magnitude of this reduction was greater in the Light-period (08:00-20:00) group than in the Dark-period (20:00-08:00) group. The differentiation and proliferation of chondrocytes were inhibited in animals in the Light-period group, compared with those in the Dark-period group. These results suggest that the orthopedic effects of mandibular retractive force vary depending on the time of day the force is applied, and that such force may be more effective while animals are resting than while they are active.

Analysis of Variance↗

PubMed2001

The medaka rs-3 locus required for scale development encodes ectodysplasin-A receptor.

The bodies of most teleost fish species are covered with specialized subepithelial structures known as scales. The scale is an epithelial appendage that differentiates from the dermal mesenchyme. Mammals, on the other hand, have no scales, but instead their bodies are covered with hair. Although their appearances are quite different, scales and hair can be considered structurally similar in that both of them are epithelial appendages distributed over the body surface in an orderly pattern. This analogy suggests that they may have the same evolutionary origin. But, to date, no molecular evidence has been presented that links scales and hair. A mutation at the rs-3 locus of medaka (Oryzias latipes) leads to almost complete loss of scales. We demonstrated that the rs-3 locus encodes ectodysplasin-A receptor (EDAR), which is required for the initiation of hair development in mammals. We identified a novel transposon inserted in the first intron of EDAR, which causes aberrant splicing. This work shows that EDAR is required for scale development in fish and suggests that it is an evolutionarily conserved molecule that is required for the development of epithelial appendages in vertebrates.

Amino Acid Sequence↗

PubMed2001

A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice.

Tuberous sclerosis (TS) is characterized by the development of hamartomas in various organs and is caused by a germ-line mutation in either TSC1 or TSC2 tumor suppressor genes. From the symptomatic resemblance among TS patients, involvement of TSC1 and TSC2 products in a common pathway has been suggested. Here, to analyze the function of the Tsc1 product, we established a line of Tsc1 (TSC1 homologue) knockout mouse by gene targeting. Heterozygous Tsc1 mutant (Tsc1(+/-)) mice developed renal and extra-renal tumors such as hepatic hemangiomas. In these tumors, loss of wild-type Tsc1 allele was observed. Homozygous Tsc1 mutants died around embryonic days 10.5-11.5, frequently associated with neural tube unclosure. As a whole, phenotypes of Tsc1 knockout mice resembled those of Tsc2 knockout mice previously reported, suggesting that the presumptive common pathway for Tsc1 and Tsc2 products may also exist in mice. Notably, however, development of renal tumors in Tsc1(+/-) mice was apparently slower than that in Tsc2(+/-) mice. The Tsc1 knockout mouse described here will be a useful model to elucidate the function of Tsc1 and Tsc2 products as well as pathogenesis of TS.

Animals↗

PubMed2001

Multistep renal carcinogenesis as gene expression disease in tumor suppressor TSC2 gene mutant model--genotype, phenotype and environment.

Cancer is an inheritable disorder of somatic cells. Environment and heredity both operate in the origins of human cancer. These environmental and genetic determinants of cancer can be classified into four groups designated "Oncodemes" [1]. Oncodeme 1 is the irreducible "background" level of cancer due to spontaneous mutagenesis. Oncodeme 2 is "environmentally induced" cancer, whose causative agents are chemical carcinogens, radiation and viruses. Oncodeme 3 is basically "environmentally induced" cancer, but there are genetically determined differences among persons, e.g. the activation or inactivation of carcinogenes. Most human cancers are believed to belong to Oncodemes 2 and/or 3 (about 80%), for which the probability of the occurrence of the initial carcinogenic step(s) is increased, although the number of steps is not decreased. Oncodeme 1 would contain the approximately 20% that would remain if "environmentally induced" cancers (Oncodeme 2 and/or 3) were prevented. Lastly, Oncodeme 4 is "hereditary" cancer. Hereditary cancers could prove valuable in elucidating carcinogenesis, even though only a small proportion of cancers belong to this group. Here, we present a unique animal model of Oncodeme 4 for the study of problems in carcinogenesis; e.g. cell stage and tissue/cell-type-specific tumorigenesis, multistep carcinogenesis, species-specific differences in tumorigenesis, modifier gene(s) in renal carcinogenesis and cancer prevention.

Animals↗

PubMed2001

1,25-Dihydroxyvitamin D(3) prevents the conversion of adipose tissue into fibrous tissue in skin exposed to chronic UV irradiation.

The hormonally active form of vitamin D (1,25(OH)2D3) is known to be a physiological regulator of the proliferation and differentiation of skin cells including keratinocytes, fibroblasts, and adipocytes. In the present study, the efficacy of 1,25(OH)2D3 on the conversion of adipose tissue to fibrous tissue in photodamaged skin was investigated in a murine animal model. Groups of hairless mice were exposed to solar-simulating UV irradiation (lambdamax, 352 nm; UV distribution: 300-310 nm, 0.9%; 310-320 nm, 2.0%; 320-420 nm, 97.1%) for 20 weeks at a dose of 10.8 J/cm2 five times weekly on weekdays. At the end of 20 weeks irradiation, wrinkling in the dorsal skin was induced. The histological and biochemical studies indicated that UV irradiation caused a disappearance of adipocytes and concomitant accumulation of the extracellular matrix components (fibrosis), including collagen, hyaluronan, and chondroitin/dermatan, which are synthesized by fibroblasts. Application of 1,25(OH)2D3 on the dorsal skin prior to UV irradiation dramatically prevented both the disappearance of adipocytes and the accumulation of extracellular matrix components in the lower dermis, resulting in antiwrinkling. These findings indicate that 1,25(OH)2D3 prevents the UV-induced abnormal differentiation and proliferation of adipocytes and fibroblasts, which arise from a common progenitor, mesenchymal cells.

Adipose Tissue↗

PubMed2001

Additional t(11;17)(q23;q21) in a patient with Philadelphia-positive mixed lineage antigen-expressing leukemia.

We describe very uncommon phenotypic and cytogenetic findings in a 40-year-old female with blast phase of Philadelphia chromosome (Ph)-positive CML. In addition to the t(9;22)(q34;q11) that was detected in all metaphases, a t(11;17)(q23;q21) was identified in 15 of 20 metaphases. Reverse transcription-polymerase chain reaction showed the major and minor bcr/abl fusion transcripts in the cells from a bone marrow (BM) sample. Fluorescence in situ hybridization (FISH) analysis also showed that fusion signals of the bcr and abl probes were found in 95% of blastic cells and in 64% of neutrophils. MLL gene rearrangement was also detected in some blastic cells but not in neutrophils by FISH analysis. Phenotypically, blastic cells expressed mixed lineage antigens such as CD34, CD33, CD13, CD19, CD7, and CD41. Immunogenotypically, some population of BM cells showed monoclonal rearrangements of immunoglobulin heavy chain and T-cell receptor gamma chain genes by Southern blot analysis. Clinical course was aggressive, and therapy was poorly tolerated. Such findings seem to support an association between Ph and an abnormality of 11q23 with poor prognosis, and suggest that the expression of both abnormal genes may be related to this mixed lineage antigen-expressing leukemia.

Adult↗