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Biomedical subjects

T Komori

Publications and source records attributed to T Komori.

At least 19 recordsLinked to original sources
PubMed2006

Complete overlap of interleukin-31 receptor A and oncostatin M receptor beta in the adult dorsal root ganglia with distinct developmental expression patterns.

Interleukin-31 receptor A (IL-31RA) is a newly identified type I cytokine receptor, that is related to gp130, the common receptor of the interleukin (IL) -6 family cytokines. Recent studies have shown that IL-31RA forms a functional receptor complex for IL-31 together with the beta subunit of oncostatin M receptor (OSMRbeta). However, little is known about the target cells of IL-31 because it remains unclear which types of cells express IL-31RA. In our previous reports, we demonstrated that OSMRbeta is expressed in a subset of small-sized nociceptive neurons of adult dorsal root ganglia (DRGs). In the present study, we investigated the IL-31RA expression in the adult and developing DRGs. From a northern blot analysis and in situ hybridization histochemistry, IL-31RA mRNA was found to be expressed in the adult DRGs. According to reverse-transcriptase polymerase chain reaction, IL-31RA mRNA was detected in the DRGs and trigeminal ganglia, while no expression of IL-31RA mRNA was observed in the CNS. Double immunofluorescence staining revealed IL-31RA to be expressed in a subset of small-sized neurons, all of which colocalized with OSMRbeta. In addition, the expression of IL-31 RA was detected in afferent fibers in the spinal cord and the dermis of the skin. We also found that the developmental expression pattern of IL-31RA was different from that of OSMRbeta; IL31RA-positive neurons in DRGs first appeared at postnatal day (PN) 10 and reached the adult level at PN14, whereas OSMRbeta-positive neurons were observed at PN0 for the first time. We previously demonstrated OSMRbeta-expressing neurons to decrease, however, they were not found to disappear in oncostatin M (OSM) -deficient mice. These findings suggest that IL-31 and OSM may thus have redundant functions in the development of OSMRbeta-expressing neurons.

Aging↗
PubMed2006

Induction of brain-derived neurotrophic factor by leptin in the ventromedial hypothalamus.

Leptin, an adipocyte-derived hormone, reduces food intake by regulating orexigenic and anorexigenic factors in the hypothalamus. Although brain-derived neurotrophic factor is an important anorexigenic factor in the hypothalamus, little is known about the regulation of brain-derived neurotrophic factor expression by leptin in the hypothalamus. In the present study, we examined the effect of leptin on the expression of brain-derived neurotrophic factor in the hypothalamus. I.V. administration of leptin (10 microg/g) led to the increase in the expression of brain-derived neurotrophic factor mRNA, which was observed in the dorsomedial part of the ventromedial hypothalamic nucleus. The increased expression of brain-derived neurotrophic factor mRNA was detected in phosphorylated signal transducer and activator of transcription 3-positive neurons, suggesting that leptin induced brain-derived neurotrophic factor expression in neurons of the dorsomedial part of the ventromedial hypothalamic nucleus. In addition, the expression of brain-derived neurotrophic factor was increased at the protein level in the ventromedial hypothalamic nucleus of leptin-injected mice. Interestingly, brain-derived neurotrophic factor-positive fibers also increased in the ventromedial hypothalamic nucleus and dorsomedial hypothalamic nucleus of leptin-injected mice, which were in close apposition to tyrosine kinase receptor B-immunoreactive neurons and colocalized with synaptophysin, a marker of presynaptic terminals. These results suggest that leptin induces brain-derived neurotrophic factor expression in the dorsomedial part of the ventromedial hypothalamic nucleus and brain-derived neurotrophic factor may exert as anorexigenic factors possibly through the activation of tyrosine kinase receptor B in the ventromedial hypothalamic nucleus and dorsomedial hypothalamic nucleus.

Animals↗
PubMed2005

A comparison of brachytherapy and surgery for the treatment of stage I-II squamous cell carcinoma of the tongue.

The treatment method for early stage tongue cancer is still controversial in Japan. The aim of this study is to compare the prognosis for patients with early tongue cancer treated with brachytherapy and surgery. A retrospective study was conducted to compare the efficacy of low-dose-rate brachytherapy (LDR), high-dose-rate brachytherapy (HDR), and surgery for early tongue cancer. A total of 180 patients with stage I-II tongue cancer were divided into three treatment groups: LDR (78), HDR (26), and surgery (71). Local recurrence was seen in thirteen patients (17%) of the LDR, nine (35%) of the HDR, and four (6%) of the surgery group. After salvage therapy, final local cure was obtained for 71 patients (91%) of the LDR, 22 (85%) of the HDR, and 71 (100%) of the surgery group. Neck failure was recorded for eight patients in the LDR, six in the HDR, and three in the surgery group. The respective 5-year overall survival rates for the LDR, HDR and surgery groups were 84.0%, 72.9%, 95.4% for stage I, and 72.2%, 51.5%, 93.8% for stage II. These findings show that surgery is the optimal treatment method for patients with stage I-II tongue cancer.

Adolescent↗
PubMed2005

Hemodynamic infarction of the spinal cord: involvement of the gray matter plus the border-zone between the central and peripheral arteries.

OBJECTIVE: Hemodynamic infarction of the spinal cord that affected an 81-year-old female having a dissecting aortic aneurysm is presented. During the graft replacement operation, systemic hypotension occurred and the patient was subsequently complicated with paraplegia of the lower limbs. The patient died 2 weeks after the surgery due to gastrointestinal bleeding. An autopsy, which did not include the brain, was performed and the spinal cord was sampled. The aim of this report is to describe the pathologic profile of the spinal cord of the patient, and to gain insight into the pathogenesis of the lesion. METHODS: Histochemical and immunohistochemical methods were employed to study the spinal cord ranging from the lower thoracic to sacral segments. RESULTS: The whole central areas of the spinal cord showed coagulation and/or liquefaction necroses, while the white matter on the circumference of the cord remained unaffected, thus exhibiting a 'ring-like' appearance. CONCLUSION: This case is an example of hemodynamic infarction of the spinal cord involving the gray matter that is supplied by the central artery, plus the border-zone that is supplied by both the central and peripheral arteries. The former is probably associated with selective vulnerability of the gray matter to ischemia, while the latter is probably associated with intrinsic vulnerability of the border-zone to systemic hypotension or low blood-flow states.

Aged↗
PubMed2005

Experimental study on the morphological and functional recovery following partial glossectomy in rabbits: a comparison between CO2 laser and electrocautery.

OBJECTIVE: The aim of the present study was to evaluate and compare the morphological and functional recovery following partial glossectomy in rabbits with the CO(2) laser and electrocautery. METHODS: Partial glossectomy with the CO(2) laser or electrocautery in rabbits was performed to investigate changes in the body weight and tongue width after surgery. The study models were classified into three groups. In group 1, the excised edges of the wound were left unsutured after partial glossectomy with the CO(2) laser. In group 2, the wound was closed after CO(2) laser surgery. In group 3, as a control group, the wound was closed after partial glossectomy with electrocautery. The specimens of the tongues obtained from the rabbit were microscopically assessed. RESULTS: No significant differences were found in the percent change in the body weight among the three groups. There was a significant difference in the tongue width between groups 1 and 3 at each time point: 2 weeks (p < 0.05), 4 weeks (p < 0.01), and 8 weeks (p < 0.001) postoperatively. Furthermore, there was a significant difference in the tongue width between groups 2 and 3 at 8 weeks (p < 0.02) postoperatively. Histologically, the scar tissue of the wound was extensive in the control group, although it was localized in the laser group. CONCLUSION: Postoperative dysfunction was reduced when excised edges were left unsutured after partial glossectomy with the CO(2) laser.

Animals↗
PubMed2004

Runx2-deficient mice lack mandibular condylar cartilage and have deformed Meckel's cartilage.

Runx2 (runt-related transcription factor 2) deficient mice lacked the mandibular condylar cartilage and the mandibular bone. The anlage of the condylar process consisted of mesenchymal condensation, which expressed Type I collagen mRNA and alkaline phosphatase activity, but not Type II collagen and aggrecan mRNAs. Therefore, the differentiation of the mandibular condylar cartilage stopped at the preosteoblast (skeletoblast) stage. The lateral pterygoid muscle was attached to this anlage, and relatively abundant mesenchymal condensations were also formed at the muscle-attaching sites, e.g. the anlage of the mandibular body, the angular and coronoid processes. Three-dimensional reconstruction models showed that each mesenchymal condensation was connected to one another, and roughly outlined the shape of the mandible. Meckel's cartilage in the Runx2-deficient mice had two ectopic cartilaginous processes to which the digastric and myohyoid muscles were attached. These findings indicate that Runx2 is essential for the formation of the mandibular condylar cartilage, as well as for normal development of Meckel's cartilage and that muscle tissues influence mandible morphology.

Alkaline Phosphatase↗
PubMed2004

mRNA expression and protein localization of dentin matrix protein 1 during dental root formation.

Dentin matrix protein 1 (DMP1) is an acidic phosphoprotein. DMP1 was initially detected in dentin and later in other mineralized tissues including cementum and bone, but the DMP1 expression pattern in tooth is still controversial. To determine the precise localization of DMP1 messenger RNA (mRNA) and the protein in the tooth, we performed in situ hybridization and immunohistochemical analyses using rat molars and incisors during various stages of root formation. During root dentin formation of molars, DMP1 mRNA was detected in root odontoblasts in parallel with mineralization of the dentin. However, the level of DMP1 mRNA expression in root odontoblasts decreased near the coronal part and was absent in coronal odontoblasts. DMP1 protein was localized along dentinal tubules and their branches in mineralized root dentin, and the distribution of DMP1 shifted from the end of dentinal tubules to the base of the tubules as dentin formation progressed. During the formation of the acellular cementum, DMP1 mRNA was detected in cementoblasts lining the acellular cementum where its protein was localized. During the formation of the cellular cementum, DMP1 mRNA was detected in cementocytes embedded in the cellular cementum but not in cementoblasts, and its protein was localized in the pericellular cementum of cementocytes including their processes. During dentin formation of incisors, DMP1 mRNA was detected in odontoblasts on the cementum-related dentin, where its protein was localized along dentinal tubules near the mineralization front. The localization of DMP1 mRNA and protein in dentin and cementum was related to their mineralization, suggesting that one of the functions of DMP1 may be involved in the mineralization of dentin and cementum during root formation.

Animals↗
PubMed2004

Isolation and characterization of a mesenchymal cell line that differentiates into osteoblasts in response to BMP-2 from calvariae of GFP transgenic mice.

We established the clonal mesenchymal cell line, GFP-C3 (C3), which differentiates into osteoblasts in response to BMP-2 from calvariae of newborn green fluorescence protein (GFP) transgenic mice. This cell line cultured with control medium expressed low levels of alkaline phosphatase (ALP) activity and osterix mRNA and undetectable ALP and osteocalcin mRNA. Incubation of these cells with rhBMP-2 increased ALP activity dose-dependently and induced substantial levels of ALP, osteocalcin and osterix mRNA expression. C3 cells infected with adenovirus vector encoding BMP-2 (AdBMP-2) or Runx2 (AdRunx2) showed greatly increased ALP mRNA expression in a time-dependent fashion. Transduction with AdRunx2-induced expression of ALP and osteocalcin mRNA, but not osterix mRNA by day 3. Transduction with AdBMP-2 induced apparent expression of ALP and osterix mRNA by day 1 after transduction, but induced only weak expression of osteocalcin mRNA day 3 after transduction. Transplantation of C3 cells transduced with AdBMP-2 into back subfascia in wild-type mice with a complex of poly-d,l-lactic-co-glycolic acid/gelatin sponge (PGS) generated ectopic bone formation involving GFP-positive osteoblasts and osteocytes 2 weeks after transplantation. C3 cells transduced with AdRunx2 or AdLacZ failed to induce ectopic bone formation. Transplantation of C3 cells transduced with AdBMP-2 into craniotomy defects in wild-type mice using PGS as a carrier induced bone formation 2 weeks after transplantation, and replaced defects 4 weeks after transplantation. C3 cells transduced with AdRunx2 failed to induce bone repair after transplantation into craniotomy defects. These results indicate that C3 cells retain differentiation potential into osteoblasts in response to BMP-2. They are useful tools for analyzing the process of osteoblast differentiation in vivo after transplantation.

Animals↗
PubMed2004

Expression of dentin matrix protein 1 (DMP1) during fracture healing.

Dentin matrix protein 1 (DMP1) is one of the acidic phosphorylated extracellular matrix proteins called the SIBLING (small integrin-binding ligand, N-linked glycoproteins) family. Recent studies showed that DMP1 is expressed in the mineralized tissues and suggested that DMP1 is involved in the mineralization. We investigated the precise localization of DMP1 messenger RNA (mRNA) and protein during fracture healing. In situ hybridization demonstrated that DMP1 mRNA was strongly expressed in preosteocytes and osteocytes in the bony callus during intramembranous and endochondral ossification while DMP1 mRNA was not detected in osteoblasts and chondrocytes. During endochondral ossification, however, a low number of DMP1-expressing cells were identified in the cluster of hypertrophic chondrocytes. However, these DMP1-expressing cells were not hypertrophic and were likely to be osteoblast-lineage cells, which were embedded in the matrix of bone or cartilage, because type I collagen-expressing cells and invasion of capillary vessels were observed in the same area. Northern blot, in situ hybridization, and immunohistochemical analyses showed that DMP1 mRNA and protein expressions were increased until day 14 postfracture, when bony callus was formed, and then declined to a lower level during remodeling of the bony callus. Therefore, DMP1 is likely to play an important role in the mineralization of the bony callus.

Animals↗
PubMed2004

Metformin ameliorates treatment of obese type 2 diabetic patients with mental retardation; its effects on eating behavior and serum leptin levels.

The metabolic effects of a biguanide, metformin, on glycemic control and eating behavior were investigated in 16 type 2 diabetic subjects with mental retardation who were habitual overeaters and had difficulty in controlling their appetites. The subjects (n = 16) received metformin (750 mg/day) for 6 months and body weight, body mass index (BMI) were measured monthly. They had repetitive metabolic and hormonal studies. Their eating behavior was analyzed by questionnaires given by their guardians before and after treatment. Metformin treatment significantly reduced their body weights (p < 0.01), body mass index (BMI) (p < 0.01), the levels of HbA1c (p < 0.001), fasting blood glucose (FBG) (p < 0.05), serum insulin (p < 0.05), C-peptide (p < 0.01), triglyceride (p < 0.01), and total cholesterol (p < 0.05). Insulin resistance index (FBG (mg/dl) x serum insulin levels ( micro U/ml) x 1/405) was significantly reduced after 1-month treatment. The serum leptin levels were significantly decreased after 4 month's treatment and thereafter (p < 0.05). Analysis of the questionnaires before and after treatment showed that the daily intake of regular and additional foods significantly decreased after treatment (p < 0.01 and p < 0.001, respectively) with improvements of eating behavior. We conclude that metformin may have beneficial effects not only to control glycemia but also to correct eating behavior in obese type 2 diabetic patients with the difficulty in controlling their appetites. The improvement was related to the reduction of insulin resistance and serum leptin levels.

Adult↗
PubMed2004

Identification of differentially expressed genes involved in colorectal carcinogenesis using a cDNA microarray.

To identify candidate genes involved in human colorectal carcinogenesis, we constructed the gene expression profiles of 50 colorectal cancers (CRCs) and 12 normal colorectal epithelia using a cDNA microarray specially constructed for CRC. Hierarchical clustering analysis and principal component analysis could clearly distinguish the gene profiles of cancer tissues from those of normal tissues. Our results confirm there are indeed differences in gene expression between cancer and normal mucosa. Our cDNA microarray identified 22 up-regulated genes and 32 down-regulated genes in CRC. Many of these genes have been previously identified in relation to human carcinogenesis, 68% and 78%, respectively. Subsequent validation of selected genes by serial analysis of gene expression and reverse transcription polymerase chain reaction, demonstrated expression patterns that were almost identical to our microarray analysis. Using a four-fold larger sample relative to that used in our previous study, candidate genes involved in human colorectal carcinogenesis were reproducibly identified. Further studies of comprehensive gene expression using our technique may elucidate the mechanism of CRC tumorigenesis.

Cell Line, Tumor↗
PubMed2003

Neuropathological analysis in spinal muscular atrophy type II.

We performed a neuropathological analysis, including in situ nick end labeling (ISEL) and immunohistochemistry, of two cases of clinicogenetically confirmed infantile spinal muscular atrophy (SMA) type II. Both cases showed severe reduction of the motor neurons and gliosis in the spinal cord and brain stem, although the occurrences of central chromatolysis and ballooned neurons were not frequent. Clark's and lateral thalamic nuclei, which are usually altered in SMA type I, were spared, whereas Betz cells in the precentral gyrus and large myelinated fibers in the lateral funiculus were reduced in number. Regarding apoptosis, only the younger case demonstrated a few ISEL-positive nuclei in the dorsal horn, with reduced Bcl-x expression level in the Purkinje cells. Unlike SMA type I, the expression of neurofilaments was not disturbed and the reduction in synaptophysin expression level in the anterior horn was mild. An oxidative stress-related product was deposited in atrophic motor neurons in the spinal cord, and neurons with nuclei immunoreactive for 8-hydroxy-2'-deoxyguanosine were found in the lateral thalamus. In contrast, the expression of glial glutamate transporters was not altered. These data suggest that oxidative stress and, to a lesser extent, apoptotic cell death, but not disturbed neurofilament metabolism or excitotoxicity, may be involved in neurodegeneration in SMA type II.

Adult↗
PubMed2003

Laser surgery as a treatment for oral leukoplakia.

Various treatment procedures for oral leukoplakia have been reported. However, after some treatments, oral leukoplakia show recurrence and/or malignant transformation, even following complete resection. Furthermore, patients with oral leukoplakia may develop new lesions in other oral cavity locations. Laser surgery for oral mucosal lesions has been reported to have many advantages, and it is widely used in the treatment of oral leukoplakia. In previous studies, recurrence and malignant transformation from the lesion have occasionally been observed following laser surgery. We reviewed the records of oral leukoplakia patients treated with laser surgery to assess its clinical usefulness. It has been reported that the rate of recurrence was 7.7-38.1%, while malignant transformation was 2.6-9% for oral leukoplakia treated with laser surgery. In the present study, there was 29.3% recurrence and 1.2% malignant transformation after laser surgery. This was similar to previous findings. This suggests that non-homogeneous leukoplakia on nonkeratinized epithelia, i.e. the tongue mucosa has a high risk for malignant transformation, so lesions should be excised after detecting abnormal epithelia using vital tissue staining. The wound healing process after laser surgery was satisfactory and no significant complications were observed. Management of oral leukoplakia prevents not only recurrence and malignant transformation, but also postoperative dysfunction: laser surgery is an excellent procedure that is able to overcome these problems.

Adult↗
PubMed2003

Transplantation of skin fibroblasts expressing BMP-2 promotes bone repair more effectively than those expressing Runx2.

We investigated the osteogenic potential of skin fibroblasts that overexpressed BMP-2 or Runx2 by using adenoviral vectors. In in vitro experiments, skin fibroblasts infected with adenovirus vector encoding BMP-2 (AdBMP-2) released substantial levels of BMP-2 proteins into culture media, and those infected with adenovirus vector encoding Runx2 (AdRunx2) produced its protein. Transduction of BMP-2 or Runx2, respectively, increased alkaline phosphatase (ALP) activity and induced expression of mRNAs of ALP, osteocalcin, and osterix in skin fibroblasts. In in vivo experiments, we investigated the bone induction activity by transplantation of a complex composed of carrier [poly-D,L-lactic-co-glycolic acid/gelatin sponge (PGS)] and skin fibroblasts (PGS/SF complex). Transplantation of PGS/SF complexes composed of skin fibroblasts transduced with AdBMP-2-induced ectopic bone formation when transplanted into the subfascia of back muscle, unlike those infected with AdRunx2. Transplantation of PGS/SF complexes composed of skin fibroblasts transduced with AdBMP-2 into craniotomy defects induced bone formation from 2 weeks after transplantation, and almost all PGS was replaced by newly synthesized bone at 6 weeks. To investigate the fate of the transplanted cells, we transplanted skin fibroblasts isolated from green fluorescence protein transgenic mice into craniotomy defects. Transplantation of these skin fibroblasts transfected with AdBMP-2 generated green fluorescence protein-positive osteoblasts and osteocytes, indicating that the transplanted skin fibroblasts differentiated into osteoblastic lineage cells during bone repair. In contrast, transplantation of PGS/SF complexes composed of skin fibroblasts transduced with AdRunx2 induced a few ALP-positive cells at 1 week after transplantation, but their number decreased depending on time after transplantation. In addition, transplantation of these complexes was insufficient to induce bone repair. Taken together, our results suggest that skin fibroblasts expressing BMP-2 are more suitable for cell-mediated therapy of bone repair than those expressing Runx2.

Adenoviridae↗
PubMed2003

In vitro effect of platelet-derived growth factor-BB on collagen synthesis and proliferation of human periodontal ligament cells.

OBJECTIVES: Platelet-derived growth factor (PDGF)-BB is a polypeptide growth factor which has been shown to stimulate periodontal regeneration. In this study, we investigated the time- and dose-dependent effect of PDGF-BB on the proliferation and collagen synthesis of human periodontal ligament (PDL) cells. MATERIALS AND METHODS: For the proliferation assay, PDL cells were cultured in 0.01-10 ng ml(-1) of PDGF-BB for 12 or 24 h, and cell numbers were counted. For the collagen synthesis assay, PDL cells were cultured in 0.1-10 ng ml(-1) of PDGF-BB for 1 to 24 h. The ratio of collagen content in total protein was evaluated, and the gene expression of type I collagen was assessed quantitatively by Northern blotting analysis. RESULT AND CONCLUSIONS: PDGF-BB stimulated the proliferation of PDL cells in a time- and dose-dependent manner with the maximum effect at 10 ng ml(-1). PDGF-BB induced the collagen synthesis of PDL cells with the maximum effect for 24-h treatment, and 1 ng ml(-1) of PDGF-BB. PDGF-BB exhibits an inverse dose-dependent effect on proliferation and collagen synthesis by PDL cells. These findings suggest that PDGF-BB is one of the important regulators of the maintenance of the extracellular matrix in PDL, and may play an important role in the regeneration of PDL.

Becaplermin↗
PubMed2003

Runx2 expression and action in chondrocytes are regulated by retinoid signaling and parathyroid hormone-related peptide (PTHrP).

OBJECTIVE: Runx2 (also known as Cbfa1) is a transcription factor required for chondrocyte maturation and osteoblast differentiation. While there is information on the regulation of its expression during osteogenesis, much less is known about it during cartilage maturation. Here we asked whether Runx2 expression and function are affected by retinoic acid (RA) and parathyroid hormone-related peptide (PTHrP), which represent an important stimulator and inhibitor of chondrocyte maturation, respectively. DESIGN: We first cloned and characterized Runx2 expressed by chick chondrocytes (cRunx2). We then constructed expression vectors of cRunx2 and a dominant-negative form (DN-cRunx2) and determined their effects on chondrocyte maturation in culture before and during retinoid and PTHrP treatment. RESULTS: cRunx2 showed similar transactivation activity to that of its mammalian counterparts although it has a very short QA domain and lacks a small portion of the PST domain. cRunx2 over-expression stimulated chondrocyte maturation, as indicated by increases in alkaline phosphatase activity (APase), mineralization, and type X collagen and MMP-13 expression, and by maintenance of Indian hedgehog (Ihh) expression. RA treatment stimulated cRunx2 gene expression and boosted its pro-maturation effects. PTHrP treatment blocked Runx2 expression and its pro-maturation effects. Over-expression of DN-cRunx2 inhibited maturation and even prevented RA from exerting its pro-maturation role. CONCLUSIONS: As previously indicated by mammalian studies, cRunx2 has chondrocyte pro-maturation activity. Its expression and roles are favorably modulated by retinoid signaling but are completely inhibited by PTHrP. A model integrating cRunx2 with PTHrP, Ihh and retinoid signaling and operating during skeletogenesis is proposed.

Animals↗