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Biomedical subjects

T Komori

Publications and source records attributed to T Komori.

At least 91 records · Page 5Linked to original sources
PubMed2000

The role of radiotherapy for patients with adenoid cystic carcinoma of the salivary gland.

OBJECTIVE: Adenoid cystic carcinoma (ACC) is a rare malignant tumor occurring in the salivary gland that has some characteristic features, including slow growth, extremely diffuse invasion, and a high incidence of distant metastasis. The indication of radiotherapy (RT) for ACC is controversial. The aim of this study was to examine the usefulness of RT for patients with ACC. STUDY DESIGN: The study group was composed of 17 patients (18 lesions) with ACC of the salivary gland who underwent RT. They were divided into 3 groups: (1) those who underwent RT alone for a primary tumor, (2) those who underwent RT alone for a recurrent tumor after surgery, and (3) those who underwent postoperative RT because of a histologically positive surgical margin. The clinical course of each patient was examined retrospectively. RESULTS: Of the 11 patients undergoing RT alone for a primary or recurrent tumor, 5 showed complete remission of the tumor, and 3 were free from local recurrence for a long period. Seven patients who underwent postoperative RT seemed to show better local control than did those who did not undergo postoperative RT, although there were no significant differences. CONCLUSIONS: We find RT to be an effective treatment procedure, especially for those who had an inoperable, advanced tumor or who had distant metastasis. Postoperative RT was recommended for those who had a histologically positive surgical margin.

Carcinoma, Adenoid Cystic↗
PubMed2000

High-dose rate interstitial brachytherapy for stage I-II tongue cancer.

OBJECTIVE: This retrospective clinical study evaluated the usefulness of high-dose rate (HDR) brachytherapy for stage I-II tongue cancer in comparison with traditional low-dose rate (LDR) brachytherapy. MATERIALS AND METHODS: Twenty-five patients with stage I-II tongue cancer underwent HDR between 1995 and 1999. The status of local control and late neck metastasis, survival rate, and frequency of osteonecrosis in these patients were examined in comparison with a historical control made up of 71 patients who underwent LDR between 1980 and 1995. RESULTS: The local control rate and survival rate were lower in the HDR group than in the LDR group. There were no apparent differences in the frequency of late neck metastasis between the two groups. Osteonecrosis occurred earlier and more frequently in the HDR group. CONCLUSION: We would caution the use of HDR brachytherapy until further studies are done in many institutions.

Brachytherapy↗
PubMed2000

A case of local recurrent pheochromocytoma: usefulness of I-123 MIBG early SPECT and maximum intensity projection images.

It has been reported that 10% of patients with pheochromocytoma experience recurrence despite surgery. The authors administered I-123 MIBG to patients with recurrent pheochromocytoma and found that early images are more useful than delayed images to detect recurrence. Early imaging with I-123 MIBG is useful for postoperative follow-up studies in patients with pheochromocytoma and those with possible tumor recurrence.

3-Iodobenzylguanidine↗
PubMed2000

Tc-99m PMT whole-body scintigraphy for evaluated of therapeutic effect and for monitoring bone metastasis in a patient with hepatocellular carcinoma.

Detection of metastatic lesions by bone scintigraphy is highly sensitive but has a low rate of specificity. Often bone metastases from hepatocellular carcinoma are not detected by bone scintigraphy because of low uptake or a photopenic area in the tumor. In contrast, Tc-99m Sn-N-pyridoxy-5-methyltryptophan (Tc-99m PMT) whole-body scintigraphy reflects tumor viability, and the specificity of detection is so high that tumor structure can be shown well. Tc-99m PMT whole-body scintigraphy was helpful for evaluating the response to therapy and monitoring the course of the patient described here with bone metastasis from hepatocellular carcinoma.

Bone Neoplasms↗
PubMed2000

Runx2 is a common target of transforming growth factor beta1 and bone morphogenetic protein 2, and cooperation between Runx2 and Smad5 induces osteoblast-specific gene expression in the pluripotent mesenchymal precursor cell line C2C12.

When C2C12 pluripotent mesenchymal precursor cells are treated with transforming growth factor beta1 (TGF-beta1), terminal differentiation into myotubes is blocked. Treatment with bone morphogenetic protein 2 (BMP-2) not only blocks myogenic differentiation of C2C12 cells but also induces osteoblast differentiation. The molecular mechanisms governing the ability of TGF-beta1 and BMP-2 to both induce ligand-specific responses and inhibit myogenic differentiation are not known. We identified Runx2/PEBP2alphaA/Cbfa1, a global regulator of osteogenesis, as a major TGF-beta1-responsive element binding protein induced by TGF-beta1 and BMP-2 in C2C12 cells. Consistent with the observation that Runx2 can be induced by either TGF-beta1 or BMP-2, the exogenous expression of Runx2 mediated some of the effects of TGF-beta1 and BMP-2 but not osteoblast-specific gene expression. Runx2 mimicked common effects of TGF-beta1 and BMP-2 by inducing expression of matrix gene products (for example, collagen and fibronectin), suppressing MyoD expression, and inhibiting myotube formation of C2C12 cells. For osteoblast differentiation, an additional effector, BMP-specific Smad protein, was required. Our results indicate that Runx2 is a major target gene shared by TGF-beta and BMP signaling pathways and that the coordinated action of Runx2 and BMP-activated Smads leads to the induction of osteoblast-specific gene expression in C2C12 cells.

Animals↗
PubMed2000

Regulation of osteoblast differentiation mediated by bone morphogenetic proteins, hedgehogs, and Cbfa1.

Osteoblasts arise from common progenitors with chondrocytes, muscle and adipocytes, and various hormones and local factors regulate their differentiation. We review here regulation of osteoblast differentiation mediated by the local factors such as bone morphogenetic proteins (BMPs) and hedgehogs and the transcription factor, core-binding factor alpha-1 (Cbfa1). BMPs are the most potent regulators of osteoblast differentiation among the local factors. Sonic and Indian hedgehogs are involved in osteoblast differentiation by interacting with BMPs. Cbfa1, a member of the runt domain gene family, plays a major role in the processes of a determination of osteoblast cell lineage and maturation of osteoblasts. Cbfa1 is an essential transcription factor for osteoblast differentiation and bone formation, because Cbfa1-deficient mice completely lacked bone formation due to maturation arrest ofosteoblasts. Although the regulatory mechanism of Cbfa1 expression has not been fully clarified, BMPs are an important local factor that up-regulates Cbfa1 expression. Thus, the intimate interaction between local factors such as BMPs and hedgehogs and the transcription factor, Cbfa1, is important to osteoblast differentiation and bone formation.

Animals↗
PubMed2000

Epalrestat, an aldose reductase ihibitor, reduces the levels of Nepsilon-(carboxymethyl)lysine protein adducts and their precursors in erythrocytes from diabetic patients.

OBJECTIVE: To clarify the role of the polyol pathway in the intracellular formation of advanced glycation end products in human tissues, we examined the effects of epalrestat, an aldose reductase inhibitor, on the level of Nepsilon-(carboxymethyl)lysine (CML) along with 3-deoxyglucosone (3-DG) and triosephosphates in erythrocytes from diabetic patients. Plasma thiobarbituric acid-reactive substances (TBARS) were also determined as indicators of oxidative stress. RESEARCH DESIGN AND METHODS: Blood samples were collected from 12 nondiabetic volunteers, 38 untreated type 2 diabetic patients, and 16 type 2 diabetic patients who had been treated with 150 mg epalrestat/day. Blood samples were also collected from 14 of the untreated type 2 diabetic patients before and after the administration of epalrestat for 2 months. The amount of erythrocyte CML was determined by a competitive enzyme-linked immunosorbent assay, and 3-DG was measured by high-performance liquid chromatography RESULTS: In diabetic patients not treated with epalrestat, the erythrocyte CML level was significantly elevated above levels seen in nondiabetic individuals (49.9 +/- 5.0 vs. 31.0 +/- 5.2 U/g protein, P < 0.05) and was significantly lower in patients receiving epalrestat (33.1 +/- 3.8 U/g protein, P < 0.05). Similar results were observed with 3-DG. The treatment of patients with epalrestat for 2 months significantly lowered the level of erythrocyte CML (46.2 +/- 5.6 at baseline vs. 34.4 +/- 5.0 U/g protein, P < 0.01) along with erythrocyte 3-DG (P < 0.05), triosephosphates (P < 0.05), fructose (P < 0.05), sorbitol (P < 0.05), and plasma TBARS (P < 0.05) without changes in plasma glucose and HbA(1c) levels. A positive correlation was evident between the erythrocyte CML and sorbitol (r = 0.49, P < 0.01) or fructose (r = 0.40, P < 0.05) levels in diabetic patients. CONCLUSIONS: The results indicate that epalrestat administration lowers CML and associated variables and that polyol metabolites are correlated with CML in the erythrocytes of diabetic patients. The observed results suggest that aldose reductase activity may play a substantial role in the intracellular formation of CML in the mediation of reactive intermediate metabolites and oxidative stress.

Aldehyde Reductase↗
PubMed2000

[Infections with drug resistant bacteria and their treatment methods--VRE infections].

Vancomycin-resistant enterococci(VRE) is a worldwide threat now. Because we have lost a last resort vancomycin for enterococcal infections, and their resistant genes can be transferred to other more pathogenic gram-positive bacteria. We have only a few of optional therapeutic agents against VRE. VRE causes urinary tract infections, intra-abdominal infections, bacteremias, endocarditis and wound infections. Especially bacteremias caused by VRE result in high mortality. VRE infections including colonization and infectious diseases must be controlled by rapid detection of VRE, appropriate diagnosis of infections, followed by effective antimicrobial therapies and infection control measures.

Enterococcus↗
PubMed2000

Establishment of a novel human squamous cell carcinoma cell line from oral primary tumor by geneticin treatment.

A novel cultured cell line NOS-1, derived from a human oral primary squamous cell carcinoma (SCC) of the lower gingiva, was established without xenografting the tumor into nude mice by means of "Geneticin" treatment, which allowed for elimination of contaminated fibroblasts and produced enriched tumor cells at an early stage of the culture. NOS-1 cells showed numerous desmosome structures and some intermediate filaments. To determine tumorigenicity and to establish an orthotopic tissue invasion model for oral carcinoma, the NOS-1 cells were injected into the back and the tongue of male athymic nude mice. The back tumors showed an expansive growth pattern without significant invasion of surrounding tissues, while the tongue-implanted tumors exhibited invasive growth. The establishment of a novel oral primary tumor cell line and a new orthotopic tissue invasion model is expected to be useful for the study of biological characterization and for the identification of the invasive mechanism of human oral cancers.

Animals↗
PubMed2000

Tensile stress induced osteoblast differentiation and osteogenesis in mouse calvarial suture in culture: possible involvement of BMP-4 and other genes.

Mechanical stress is one of the most potent inducer of bone formation. The mechanism by which cells receive and transduce the signal into osteogenesis, however, remains unknown. Previous studies have demonstrated that mechanical stress causes changes in expression levels of many genes in osteoblasts and osteocytes both in vivo and in vitro. However, none of these changes are specific to bone cells. Moreover it is not clear which types of cells contributed to the increased osteoblasts induced by mechanical stress. The purpose of this study, therefore, was to identify which cells differentiate into osteoblasts and to examine how the expression of genes that are specific to osteogenic cells changes.

Animals↗
PubMed1999

Effects of restraint stress on alpha(1) adrenoceptor mRNA expression in the hypothalamus and midbrain of the rat.

We examined the effects of restraint stress on alpha(1) adrenoceptor mRNA expression in the rat brain using reverse transcriptase-polymerase chain reaction (RT-PCR). After rats had been restrained for 10, 30, 60, 120 or 240 min, the hypothalamus and midbrain were removed immediately and alpha(1) adrenoceptor mRNA levels in these regions were determined by RT-PCR. Blood samples were also collected for simultaneous measurement of serum adrenocorticotropic hormone (ACTH) and corticosterone. Restraint stress resulted in a variety of changes in the hypothalamus and midbrain. In the hypothalamus, 30 and 60 min of stress resulted in a significant fall in the level of alpha(1) adrenoceptor mRNA relative to the control. This was associated with a rise in serum ACTH and corticosterone. In the midbrain, significant elevation of alpha(1) adrenoceptor mRNA was noted after 60, 120 and 240 min of restraint stress. Our findings indicated that the influence of restraint stress on alpha(1) adrenoceptor mRNA level in the hypothalamus is different to that of the midbrain region in rats.

Adrenocorticotropic Hormone↗
PubMed1999

Isolation and characterization of the distal promoter region of mouse Cbfa1.

Cbfa1 is an essential transcription factor for bone formation, and as such little is known about the region responsible for the transcriptional regulation of this gene. Here we report the determination of the transcription start sites, isolation and partial characterization of distal promoter region of this gene. Three transcription start sites were identified by the 5'-Cap site method, recently invented for rapid examination of the 5'-end of genes of interest. A reporter construct containing 1.8 kb of 5' of transcription start sites had approximately 25-fold more luciferase activity than the promoter-less vector in osteoblastic cell lines. Deletion analysis of the reporter construct demonstrated that the minimal region to express promoter activity lies between bp -168 and -99, taking the most downstream transcription start site as +1. By Northern blot analysis, mRNA expression from the distal promoter was detected in the differentiated osteoblastic cell lines, UMR-106, ROS17/2.8 and MC3T3-E1, but not in cell lines of immature phenotype or originated from other organs. Luciferase activity was strongest in UMR-106 and ROS17/2.8, and weakest in COS-1 and HepG2, which are cell lines originating from other organs, corresponding to the level of mRNA expression. These results demonstrated that the distal promoter region examined here is important for tissue- and cell-type-specific gene expression of Cbfa1.

Animals↗
PubMed1999

Effects of single and repeated stresses on the expression of mRNA for alpha1-adrenoceptors in the rat hypothalamus and midbrain.

We examined the effects of single or repeated stress on the expression of mRNA for alpha1-adrenoceptors in the rat hypothalamus and midbrain using the reverse transcriptase-polymerase chain reaction (RT-PCR). Single stress significantly increased the mRNA level for alpha1-adrenoceptors in the midbrain, but had no effect on mRNA levels in the hypothalamus. Repeated stress significantly decreased mRNA levels for alpha1-adrenoceptors in both regions.

Animals↗
PubMed1999

An aldose reductase inhibitor prevents the glucose-induced increase in PDGF-beta receptor in cultured rat aortic smooth muscle cells.

To examine the role of platelet-derived growth factor (PDGF) and the polyol pathway in the growth activity of smooth muscle cells (SMCs), [(3)H]-thymidine incorporation, [(125)I]-PDGF-BB binding and expression of PDGF-beta receptor protein were measured in rat aortic SMCs cultured with 5.5 or 20 mM glucose with or without anti-PDGF antibody or an aldose reductase inhibitor, epalrestat. SMCs cultured with 20 mM glucose demonstrated an accelerated thymidine incorporation compared with SMCs cultured with 5.5 mM glucose, which was prevented by anti-PDGF antibody. This acceleration of growth activity by 20 mM glucose was accompanied by an increase in PDGF-BB binding, which was due to the increased number of PDGF-beta receptors and the overexpression of PDGF-beta receptor protein. Epalrestat prevented all these abnormalities. These observations suggest that polyol pathway hyperactivity plays an important role in the proliferation of SMCs which may be mediated through the accelerated expression of PDGF-beta receptor protein.

Aldehyde Reductase↗
PubMed1999

Cbfa1 isoforms exert functional differences in osteoblast differentiation.

Cbfa1 is an essential transcription factor for osteoblast differentiation and bone formation. We investigated functional differences among three isoforms of Cbfa1: Type I (originally reported as Pebp2alphaA by Ogawa et al. (Ogawa, E., Maruyama, M., Kagoshima, H., Inuzuka, M., Lu, J., Satake, M., Shigesada, K., and Ito, Y. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 6859-6863), Type II (originally reported as til-1 by Stewart et al. (Stewart, M., Terry, A., Hu, M., O'Hara, M., Blyth, K., Baxter, E., Cameron, E., Onions, D. E., and Neil, J. C. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 8646-8651), and Type III (originally reported as Osf2/Cbfa1 by Ducy et al. (Ducy, P., Zhang, R., Geoffroy, V., Ridall, A. L., and Karsenty, G. (1997) Cell 89, 747-754). A reverse transcriptase-polymerase chain reaction analysis demonstrated that these isoforms were expressed in adult mouse bones. The transient transfection of Type I or Type II Cbfa1 in a mouse fibroblastic cell line, C3H10T1/2, induced the expression of alkaline phosphatase (ALP) activity. This induction was synergistically enhanced by the co-introduction of Xenopus BMP-4 cDNA. In contrast, the transient transfection of Type III cDNA induced no ALP activity. In C3H10T1/2 cells stably transfected with each isoform of Cbfa1, the gene expression of ALP was also strongly induced in cells transfected with Type I and Type II Cbfa1 but not in cells with Type III Cbfa1. Osteocalcin, osteopontin,and type I collagen gene expressions were induced or up-regulated in all of the cells stably transfected with each isoform of Cbfa1, and Type II transfected cells exhibited the highest expression level of osteocalcin gene. A luciferase reporter gene assay using a 6XOSE2-SV40 promoter (6 tandem binding elements for Cbfa1 ligated in front of the SV40 promoter sequence), a mouse osteocalcin promoter, and a mouse osteopontin promoter revealed the differences in the transcriptional induction of target genes by each Cbfa1 isoform with or without its beta-subunit. These results suggest that all three of the Cbfa1 isoforms used in the present study are involved in the stimulatory action of osteoblast differentiation, but they exert different functions in the process of osteoblast differentiation.

Animals↗