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Biomedical subjects

K Hata

Publications and source records attributed to K Hata.

At least 19 recordsLinked to original sources

Association of candidal activity with denture use and salivary flow in symptom-free adults over 60 years.

The purpose of this study was to examine the amount of palatal mucosa Candida species associated with denture use and stimulated salivary flow in symptom-free adults over 60 years. The subjects were 351 (189 men and 162 women) independently living elderly people with a mean age of 66.7 +/- 4.3 (SD) years. Candidal activity of palatal mucosa was evaluated by the pH change in the medium that was associated with the acid production of the yeast. Subjects whose stimulated salivary flow rate was less than 0.5 ml/min were placed in the hyposalivation group. A multiple logistic regression analysis was used to determine if an independent variable was statistically significant after controlling for other variables. Candidal activity of the palatal mucosa was significantly associated with the dental status of the maxillae (Kruskal-Wallis test, P < 0.001), but was not significantly associated with age or drug intake. In maxillary denture wearers, Candidal activity of palatal mucosa had a significantly positive correlation with candidal activity of tissue fitting surfaces of maxillary dentures (r = 0.806, P < 0.001). A multiple logistic regression analysis showed that high candidal activity of the palate was significantly associated with being male and wearing maxillary removable dentures. Stimulated salivary flow rate was likely to be negatively related to high candidal activity (P = 0.07). This study suggests that the activity of Candida species in the oral cavity is associated with the wearing of removable dentures and stimulated salivary flow, independent of age or gender even in the relatively healthy elderly.

Aged↗

Evolution of the vertebrate DNMT3 gene family: a possible link between existence of DNMT3L and genomic imprinting.

DNA methylation plays an essential role in genomic imprinting observed in eutherian mammals and marsupials. In mouse, one of the two de novo DNA methyltransferases, Dnmt3a, and a related protein, Dnmt3L have been shown to be essential for imprint establishment in the parental germline. To gain insights into the evolution of imprinting mechanisms, we have identified and characterized the DNMT3 family genes in other vertebrate species. We cloned cDNAs for chicken DNMT3A and DNMT3B, whose putative protein products shared 81.5% and 48.6% amino acid sequence identity with their mouse orthologues. Using computer-assisted database searches, we also identified DNMT3A and DNMT3B orthologues in fish (fugu and zebrafish) and marsupials (opossum). We found that, while opossums had an orthologue for DNMT3L, chickens and fish did not have this gene. Thus, unlike the other DNMT3 members, DNMT3L was restricted to the species in which imprinting occurs. The acquisition of DNMT3L by a common ancestor of eutherians and marsupials might have been closely related to the evolution of imprinting.

Amino Acid Sequence↗

Signaling mechanisms of axon growth inhibition.

Generally, the axons in the adult mammalian central nervous system (CNS) do not regenerate after injuries. This lack of regeneration results in partial disability or complete paralysis. To date, several axon growth inhibitors that are known to inhibit axon regeneration in the CNS have been identified in the myelin. Recent research has revealed the molecular mechanisms underlying the action of these inhibitors. RhoA and Rho-kinase--a downstream effector of RhoA--are key signals that elicit axon inhibition. These findings provide a number of promising strategies to promote axon regeneration after CNS injuries. Some strategies such as Rho/Rho-kinase inhibition have proved effective in animal models. Elucidation of the complete mechanism of the signal transduction will be useful for the development of efficient therapeutic strategies against injuries of the CNS.

Animals↗

A novel culture system for porcine odontogenic epithelial cells using a feeder layer.

The growth of cells in vitro can provide useful models for investigating their behaviour and improving our understanding of their function in vivo. Although the developmental regulation of enamel matrix formation has been comprehensively analysed, the detailed cellular characteristics of ameloblasts remain unclear because of the lack of a system of long-term in vitro culture. Therefore, the establishment of odontogenic epithelial cell lines has taken on a new significance. Here, we report on a novel porcine odontogenic epithelial cell-culture system, which has permitted serial culture of these cells. Epithelial cells were harvested from third molar tooth buds in the fresh mandibles of 6-month-old pigs, and seeded on dishes in D-MEM containing 10% FBS. Before the cells reached confluence, the medium was changed to LHC-9 to select the epithelial cells. When trypsinized epithelial cells were plated together with 3T3-J2 cells as a feeder layer, the epithelial cells grew from single cells into colonies. The colonies then expanded and became confluent, and could be sub-cultured for up to 20 passages. The long-term culture cells expressed mRNA for amelogenin and ameloblastin, as well as enamelysin (MMP-20), which is a tissue-specific gene product unique to ameloblasts. These results show that the system is capable of sustaining the multiplication of odontogenic epithelial cells with the characteristics of ameloblasts.

3T3 Cells↗

Allelic loss at 19q12 and Xq11-12 predict an adverse clinical outcome in patients with mucinous ovarian tumours of low malignant potential.

Ovarian tumours of low malignant potential (LMP) are intermediate between adenomas and ovarian carcinomas. These tumours are often associated with a significantly better prognosis than ovarian carcinomas. However, a subset of these tumours can progress and become lethal. In order to seek sensitive diagnostic tools for monitoring patients after surgical operation, we performed a genome-wide scan for loss of heterozygosity (LOH) in 41 mucinous LMPs using 91 polymorphic microsatellite markers at an average interval of 50 cM across all of the human chromosomes and 25 LOH markers reportedly associated with ovarian carcinoma. In addition, we assessed whether clinicopathological parameters, microvessel density, Ki-67 labeling index, apoptotic index or p53 overexpression would be useful for predicting the postoperative outcome of LMP patients. Of the 116 markers examined, 19q12 and Xq11-12 showed significant correlation between postoperative progression-free survival time and LOH status (P<0.05). Patients with a high Ki-67 labeling index had a significantly poorer progression-free survival time than those with lower levels (P=0.042). Other clinicopathological factors and immunohistochemical analysis had no correlation with progression-free survival time in this series of patients. When the combination of LOH at 19q12 and/or Xq11-12 was assessed using Cox's regression analysis, patients with tumours that showed LOH at these positions were at greatest risk of progression (P=0.0073). These findings suggest that the identification of LOH at 19q12 and/or Xq11-12 in former mucinous LMP sites should alert the clinician to the presence of a potentially aggressive lesion in the coelomic epithelium, even if a distinction between second primary tumours or recurrence could not be determined.

Adenocarcinoma, Mucinous↗

Transplantation of cultured salivary gland cells into an atrophic salivary gland.

Patients with dry mouth have been treated with salivary substitutes and/or medications such as pilocarpine or cevimeline hydrochloride. These treatments temporarily relieve their symptoms and induce salivation from residual tissue. However, no treatment is available for the purpose of regenerating an atrophic gland. In this study, the feasibility of a cell transplantation therapy for the atrophic submandibular glands was investigated in rats. Further, the potential of cell differentiation into a useful phenotype was assessed by immunohistochemistry together with cell tracking with the fluorescent dye PKH 26. Rat submandibular glands were excised, and the salivary gland epithelial cells were cultured for 3 weeks with 3T3 cells as a feeder layer. Ductal ligation of the submandibular gland was employed to generate an atrophic gland. One week after the operation, the ligation was removed, and the cultured cells labeled with PKH 26 were injected into the atrophic submandibular glands. As a control, the cultured cells were also injected into normal submandibular glands. Two weeks after cell transplantation, the transplanted cells were detectable in both the experimental and control groups. The cells were clustered in the connective tissue between the lobules. Four weeks after transplantation, the labeled cells were detectable in the experimental group but not in the control group. In the atrophic glands, the scattered transplanted cells were observed over a broad area of the gland but localized mainly around the acini and ductal region. Immunostaining results showed a possible involvement of the transplanted cells in ductal regeneration, while neither myoepithelial nor acinar differentiations were observed within the 4 weeks since transplantation. This study demonstrated that cell transplantation to the salivary gland is feasible, and that the transplanted cells were selectively attracted to and remained in the damaged area without affecting normal tissue.

3T3 Cells↗

High pressure nmr study of dihydrofolate reductase from a deep-sea bacterium Moritella profunda.

We have investigated the effect of pressure and temperature on the structural and thermodynamic stability of a protein dihydrofolate reductase from a deep-sea bacterium Moritella profunda in its folate-bound form in the pressure range between 3 and 375 MPa and the temperature range between -5 and 30 degrees C. The on-line cell variable pressure 1H NMR spectroscopy has been used to analyze the chemical shift and signal intensity in one-dimensional 1H NMR spectra. Thermodynamic analysis based on signal intensities from protons in the core part indicates that the thermodynamic stability of Moritella profunda DHFR is relatively low over the temperature range between -5 and 30 degrees C (deltaG0=15.8 +/- 4.1 kJ/mol at 15 degrees C), but is well adapted to the living environment of the bacterium (2 degrees C and 28 MPa), with the maximum stability around 5 degrees C (at 0.1 MPa) and a relatively small volume change upon unfolding (deltaV= 66 +/- 19 ml/mol). Despite the relatively low overall stability, the conformation in the core part of the folded protein remains intact up to approximately 200 MPa, showing marked stability of the core of this protein.

Adaptation, Physiological↗

Earlier surveillance colonoscopy programme improves survival in patients with ulcerative colitis associated colorectal cancer: results of a 23-year surveillance programme in the Japanese population.

Patients with long-standing ulcerative colitis (UC) are known to have an increased risk for the development of colorectal cancer (CRC). The aim of this study was to clarify the cumulative risk for the development of dysplasia or invasive cancer and the effectiveness of surveillance colonoscopy in the Japanese population. A total of 217 patients received a total of 1027 surveillance colonoscopies between January 1979 and December 2001 at the University of Tokyo hospital. Patients with invasive cancer found in the surveillance group were compared to those referred to our hospital from the other hospitals without surveillance colonoscopy. Surveillance colonoscopy confirmed 15 patients with definite dysplasia. Of these, five were proved to have invasive cancer in the resected specimens. The cumulative risk for the development of invasive cancer at 10, 20, and 30 years was 0.5, 4.1, and 6.1%, respectively, while that for the development of definite dysplasia at 10, 20, and 30 years was 3.1, 10.0, and 15.6%, respectively. All the patients with invasive cancer in the surveillance group remained alive, while three out of four patients in the nonsurveillance group died. Our surveillance programme is useful for detecting UC-associated CRC, and survival may be improved by surveillance colonoscopy.

Adolescent↗

Rat costochondral cell characteristics on poly (L-lactide-co-epsilon-caprolactone) scaffolds.

This study was designed to examine the adhesion, proliferation, and morphology of chondrocytes on new scaffolds; and to examine these cells histologically for the ability of the chondrocytes to maintain chondrogenic properties after subcutaneous implantation into nude mice. Both 75:25 poly (L-lactide-co-epsilon-caprolactone) (75PLC) and 50:50 poly (L-lactide-co-epsilon-capro-lactone) scaffold (50PLC) were tested as a scaffold for rat costochondral resting zone chondrocytes in comparison with a type I collagen sponge scaffold (collagen scaffold). Both of the poly (L-lactide-co-epsilon-caprolactone) scaffolds (75PLC and 50PLC) were coated with type I collagen solution and the effects of the collagen coat (hybrid-PLC) were also examined. The hybrid-75PLC bound the same number of cells as the collagen scaffold, whereas the 75PLC and the 50PLC bound 60% and 50% fewer cells than the collagen scaffold, respectively. The cell growth on the scaffolds progressed with culture time in all scaffolds. Cell morphology was assessed by scanning electron microscopy for differences in the structure of cellular interaction. Chondrocytes on every scaffold maintained a spherical shape. The hybrid-PLCs were superior to the PLCs with respect to the number of cells attached. The PLCs had an advantageous degradation characteristic in that they retained their original shape better than the collagen scaffold. Additionally, in the PLCs seeded, the cells retained their integrity 4 weeks after implantation, although the volume of collagen scaffold decreased by 50%.

Animals↗

Association between minor physical anomalies and lateral ventricular enlargement in childhood and adolescent onset schizophrenia.

OBJECTIVE: The primary purpose of this study was to investigate the association between morphological abnormalities of brain and minor physical anomalies (MPAs) in childhood and adolescent onset schizophrenia. METHOD: Twenty-seven patients who had been diagnosed with schizophrenia according to DSM-IV criteria before 18 years of age were included in the study. MPAs were evaluated with the modified version of Waldrop scale (WS) by Green et al. Morphological abnormalities of brain was evaluated with ventricular-brain ratio (VBR) by using cerebral magnetic resonance imaging (MRI) examination. RESULTS: A significant positive correlation was observed between WS scores and VBRs. CONCLUSION: This result indicates a relationship between MPAs and lateral ventricular enlargement, and supports neurodevelopmental etiology in childhood or adolescent onset schizophrenia.

Adolescent↗

Patients with extraintestinal manifestations have a higher risk of developing pouchitis in ulcerative colitis: multivariate analysis.

BACKGROUND: Restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) have been the surgical treatments of choice for ulcerative colitis (UC). However, the IPAA is sometimes complicated with pouchitis. Furthermore, the cumulative risk and risk factors for developing pouchitis in patients with UC undergoing IPAA have not been reported in any Asian population. The aim of our study is to clarify the cumulative risk and risk factors for developing pouchitis in Japanese patients with UC undergoing IPAA. METHODS: Fifty-eight patients with UC undergoing IPAA were retrospectively evaluated for the presence of pouchitis, gender, age of onset, history of smoking, presence of extraintestinal manifestations (EIMs) and type of operation. The diagnosis of pouchitis was based on the pouchitis disease activity index. The cumulative risk and risk factors for developing pouchitis were assessed. RESULTS: The cumulative risks for developing pouchitis at 1 and 5 years were 9.0% and 14.4%, respectively. The estimated risks of pouchitis at 5 years was 48.1% in patients with EIMs and 4.6% in those without. Both univariate and multivariate analyses revealed that the presence of EIMs is a significant risk factor (hazard ratio 16.85, 95% confidence interval 3.12-91.00; P=0.001). CONCLUSIONS: The presence of EIMs is a significant risk factor for the development of pouchitis in Japanese patients with UC undergoing IPAA.

Colitis, Ulcerative↗

Increased expression of interleukin 17 in inflammatory bowel disease.

BACKGROUND AND AIM: Interleukin (IL) 17 is a cytokine which exerts strong proinflammatory activities. In this study we evaluated changes in IL-17 expression in the inflamed mucosa and in the serum of patients with inflammatory bowel disease (IBD). METHODS: Tissue samples were obtained endoscopically or surgically from patients with ulcerative colitis (UC) (n=20), Crohn's disease (CD) (n=20), infectious colitis (n=5), ischaemic colitis (n=8), and normal colorectal tissues (n=15). IL-17 expression was evaluated by a standard immunohistochemical procedure. Serum IL-17 levels were determined by ELISA. IL-17 mRNA expression was analysed by reverse transcriptase-polymerase chain reaction. RESULTS: IL-17 expression was not detected in samples from normal colonic mucosa, infectious colitis, or ischaemic colitis. In the inflamed mucosa of active UC and CD patients, IL-17 expression was clearly detectable in CD3(+) T cells or CD68(+) monocytes/macrophages. The average number of IL-17(+) cells was significantly increased in active UC and CD patients compared with inactive patients. IL-17 mRNA expression was not detected in normal mucosa but was detectable in the mucosa from active UC and CD patients. IL-17 was not detected in the sera from normal individuals, infectious colitis, or ischaemic colitis patients but IL-17 levels were significantly elevated in IBD patients. CONCLUSIONS: IL-17 expression in the mucosa and serum was increased in IBD patients. It is likely that IL-17 expression in IBD may be associated with altered immune and inflammatory responses in the intestinal mucosa.

Acute Disease↗

Core-binding factor alpha 1 (Cbfa1) induces osteoblastic differentiation of C2C12 cells without interactions with Smad1 and Smad5.

Core-binding factor alpha(1) (Cbfa1) is an essential transcription factor for osteoblastic differentiation and osteogenesis. Bone morphogenetic protein (BMP) is also a powerful inducer of differentiation of pluripotent mesenchymal cells to osteoblast lineage and bone formation. Recent studies suggest that Cbfa1 plays a critical role during BMP-induced osteoblastic differentiation through association with cytoplasmic BMP signaling molecules, Smads. However, other studies have suggested that Cbfa1 may exhibit its osteogenic function without interaction with Smads. Therefore, it remains unclear whether association with Smad is essential for Cbfa1 function. In this study we examine the effects of Cbfa1 on osteoblastic differentiation in the presence or absence of interactions with Smad1 or Smad5 using C2C12 undifferentiated mesenchymal cells. Cbfa1 expression was induced upon stimulation with BMP-2 in C2C12 cells. Introduction of Cbfa1 into C2C12 cells induced osteoblastic differentiation and promoted transactivation of osteocalcin gene promoter without forming the complex with Smad1 or Smad5. Furthermore, in C2C12 cells in which the association of Cbfa1 with Smad1/Smad5 was prevented by the overexpression of the natural antagonist, Smad6, Cbfa1 still induced osteoblastic differentiation and transactivated osteocalcin gene promoter, regardless of BMP-2 stimulation. These results suggest that the interactions with Smad1 or Smad5 are not essential for Cbfa1 to demonstrate its osteogenic actions. However, interactions with Smad1/Smad5 enhance these osteogenic actions of Cbfa1. Of note, BMP-2-induced or Smad-induced osteoblastic differentiation was inhibited by dominant-negative Cbfa1, suggesting that the function of Cbfa1 is critical for BMP-2-induced osteoblastic differentiation. Our results suggest that Cbfa1 is essential and also sufficient to induce osteoblastic differentiation in undifferentiated mesenchymal cells, and establishment of an association with Smad1/Smad5 enhances the osteogenic actions of Cbfa1. On the other hand, Cbfa1 expression requires the activation of Smad1/Smad5 by BMP-2.

Animals↗

Prognostic significance of ultrasound derived intratumoral peak systolic velocity in epithelial ovarian cancer.

OBJECTIVE: To evaluate the prognostic significance of ultrasound derived intratumoral peak systolic velocity in epithelial ovarian cancer. DESIGN: Color Doppler imaging and pulsed Doppler spectral analysis were used in the investigation of 49 patients with epithelial ovarian cancer (19 serous, 15 mucinous, eight endometrioid, four clear cell and three Brenner cell) immediately before laparotomy. Twenty-two were stage I, six were stage II, 17 were stage III and four were stage IV. Sections of malignant tumors were analyzed for the cellular expression of thymidine phosphorylase and the intratumoral density of microvessels by immunohistochemistry using antibodies to thymidine phosphorylase and factor VIII-related antigen, respectively. Moreover, the apoptotic index was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling method. Intratumoral peak systolic velocity was tested for correlation with patients' age at diagnosis, stage of disease, presence of a residual tumor, histological subtype and grade, thymidine phosphorylase expression, apoptotic index, microvessel count and patient survival. RESULTS: Histological grade (P = 0.025), thymidine phosphorylase expression (P = 0.044), apoptotic index (P = 0.039) and microvessel count (P = 0.014) were all significantly associated with peak systolic velocity. Stage of disease (P = 0.002), presence of residual disease (P = 0.0002) and peak systolic velocity (P = 0.041) were found by univariate Cox regression analysis to be significantly associated with a poor prognosis. Multivariate Cox regression analysis revealed that stage of disease (P = 0.006) and peak systolic velocity (P = 0.008) are independent prognostic factors. CONCLUSIONS: Intratumoral peak systolic velocity could be a preoperatively pertinent prognostic predictor of survival in patients with epithelial ovarian cancer.

Adult↗