[The relationship between disability status and scores of comprehensive geriatric assessment].
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Activities of Daily Living↗
Biomedical subjects
S Kanda
Publications and source records attributed to S Kanda.
Clinical evaluation of "veraviewpocs" digital panoramic X-ray system.
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Adult↗
Role of thrombospondin-1-derived peptide, 4N1K, in FGF-2-induced angiogenesis.
Angiogenesis involves proliferation of capillary endothelial cells and formation of lumen-containing tube-like structures. A recently established murine brain capillary endothelial cell line, IBE, can either proliferate or form tube-like structures (i.e., differentiate) in response to fibroblast growth factor-2 (FGF-2), dependent on the culture conditions. The 4N1K peptide (KRFYVVMWKK), which is derived from the C-terminal cell-binding domain of thrombospondin-1 (TSP-1), inhibited tube formation, but not proliferation of IBE cells. Polyclonal antibodies against 4N1K blocked TSP-1-induced inhibition of tube formation by IBE cells. 4N1K inhibited tyrosine phosphorylation of focal adhesion kinase and FGF-2-stimulated tyrosine phosphorylation of phospholipase C-gamma in tube-forming, but not proliferating, IBE cells. The peptide also inhibited FGF-2-induced neovascularization in mouse cornea. Our results indicate that TSP-1 may exert its inhibitory effects on angiogenesis via the C-terminal cell-binding domain containing the 4N1K sequence by inhibiting tube formation by endothelial cells.
Animals↗
Contribution of Src and Ras pathways in FGF-2 induced endothelial cell differentiation.
We have examined fibroblast growth factor (FGF) receptor-1 mediated signal transduction in differentiation of endothelial cells (EC). The activated FGFR-1 couples to Ras through two adaptor proteins, FRS2 and Shc. In FGF-2 treated proliferating EC, FRS2 as well as Shc are tyrosine phosphorylated and interact with Grb2. In contrast, in FGF-2 treated differentiating cells, Shc, but not FRS2, is engaged in Grb2-interactions. Sustained MAP kinase activity has previously been implicated in differentiation. In FGF stimulated proliferating and differentiating endothelial cells, the MAP kinase Erk2 is activated in a sustained manner. Inhibition of MEK and MAP kinase activity by PD98059 treatment of cells, still allows EC tube formation. The FGFR-1 mediates activation of protein kinase C (PKC) through direct binding and activation of phospholipase C-gamma (PLC-gamma), and has also been shown to activate the cytoplasmic tyrosine kinase Src. Treatment of the cells with the PKC inhibitor bisindolylmaleimide does not prevent tube formation. In contrast, Src kinase activity is a prerequisite for EC differentiation, since treatment of the cells with PP1, a Src family specific inhibitor, abrogates tube formation. In differentiating EC, FGF-2 induces complex formation between Src and focal adhesion kinase (FAK). These data indicate that the Ras pathway is initiated via Shc or FRS2, dependent on the cellular program. Blocking the function of Src family kinases, attenuates differentiation.
Adaptor Proteins, Signal Transducing↗
Induction of apoptotic cell death in vascular endothelial cells cultured in three-dimensional collagen lattice.
Endothelial cells derived from fetal bovine aorta (BAECs) undergo apoptosis in three-dimensional (3-D) type I collagen lattice in the absence of specific angiogenic factor. In the presence of angiogenic factor, BAECs survive and form a capillary-like tube structure in 3-D culture. In the present study we elucidate the mechanisms of BAECs apoptosis or survival and tube formation in 3-D culture. When BAECs embedded in collagen lattice were cultured with angiogenic factor (fibroblast growth factor-2 (FGF-2) or 4beta-phorbol 12-myristate 13-acetate (PMA)) in the presence of PD98059, a specific inhibitor of mitogen-activated protein kinase kinase, BAECs did not form tube structures and underwent apoptosis in collagen lattice. Function-blocking antibody against alphavbeta3 integrin also inhibited tube formation and induced apoptosis in 3-D culture in the presence of angiogenic factors. Exposure of BAECs to FGF-2 and PMA had no effect on the alphavbeta3 integrin expression but induced the activation of alphavbeta3 integrin. PD98059 attenuated alphavbeta3 integrin activation in response to angiogenic factor. KB-R8301, a hydroxamic acid-based matrix metalloproteinase (MMP) inhibitor, prevented apoptotic cell death in the absence of angiogenic factor in 3-D culture and enhanced capillary-like tube formation in the presence of angiogenic factor, which was not inhibited by the anti-alphavbeta3 integrin antibody. The results suggest that angiogenic factor-induced alphavbeta3 integrin activation through the MEK-ERK pathway regulates the BAEC fate between apoptosis and angiogenesis in collagen lattice. MMP derived from BAECs seems to play a key role in the release of cryptic ligands for alphavbeta3 integrin from intact collagen.
Angiogenesis Inducing Agents↗
Signaling via fibroblast growth factor receptor-1 is dependent on extracellular matrix in capillary endothelial cell differentiation.
Differentiation of endothelial cells, i.e., formation of a vessel lumen, is a prerequisite for angiogenesis. The underlying molecular mechanisms are ill defined. We have studied a brain capillary endothelial cell line (IBEC) established from H-2Kb-tsA58 transgenic mice. These cells form hollow tubes in three-dimensional type I collagen gels in response to fibroblast growth factor-2 (FGF-2). Culture of IBEC on collagen gels in the presence of FGF-2 protected cells from apoptosis and allowed tube formation (i.e., differentiation) but not growth of the cells. FGF-induced differentiation, but not cell survival, was inhibited by treatment of the cells with an anti-beta1-integrin IgG. Changes in integrin expression in the collagen-gel cultures could not be detected. Rather, cell-matrix interactions critical for endothelial cell differentiation were created during the culture, as indicated by the gradual increase in tyrosine phosphorylation of focal adhesion kinase in the collagen-gel cultures. Inclusion of laminin in the collagen gels led to FGF-2-independent formation of tube structures, but cells were not protected from apoptosis. These data indicate that FGF receptor-1 signal transduction in this cell model results in cell survival. Through mechanisms dependent on cell-matrix interactions, possibly involving the alpha3beta1-integrin and laminin produced by the collagen-cultured IBE cells, FGF stimulation also leads to differentiation of the cells.
Amino Acid Sequence↗
Prognostic significance of beta-microseminoprotein mRNA expression in prostate cancer.
BACKGROUND: Human beta-microseminoprotein (beta-MSP or PSP94) is a small protein secreted by prostatic epithelial cells. We recently reported the presence of low levels of beta-MSP mRNA expression and protein in most prostate cancer tissues. METHODS: Beta-MSP and mRNA expression was examined by in situ hybridization in biopsy specimens obtained from 92 patients with prostate cancer. All tissue specimens were obtained by needle biopsies prior to treatment. All patients subsequently received endocrine therapy. To estimate the influence of beta-MSP mRNA expression and three possible prognostic factors, i.e., patient age, clinical stage, and Gleason score, on time to progression under endocrine therapy, univariate and multivariate analyses were performed using Cox's proportional hazards regression model. RESULTS: Multivariate survival analysis showed that clinical stage was the strongest prognostic factor (P = 0.006) and that beta-MSP mRNA expression was the second strongest factor (P = 0.038) in 92 patients with stage B-D disease. Analysis of only 51 patients with stage D disease showed that beta-MSP mRNA expression was the only significant prognostic indicator for progression under endocrine therapy (P = 0.003). CONCLUSIONS: The presence of cells that express the beta-MSP transcript may be a novel indicator of potentially aggressive prostate cancer.
Aged↗
Development and clinical application of high performance liquid chromatography for the simultaneous determination of plasma levels of theophylline and its metabolites without interference from caffeine.
A high performance liquid chromatography (HPLC) method has been developed for the simultaneous determination of plasma levels of theophylline and its metabolites without interference from caffeine or caffeine metabolites. The method is simple and of practical use because it is applicable even to plasma samples from patients who take caffeine-containing beverages. The method was also reproducible with a coefficient of variation of less than 5% for each analyte. The levels of theophylline, determined by HPLC, were validated by their high correlation to the levels obtained by fluorescence polarization immunoassay. HPLC was used to determine theophylline levels in patients with bronchial asthma. The data revealed that the ratio of 1,3-dimethyluric acid, the major metabolite of theophylline, to theophylline concentration in the plasma was within a narrow range in most patients (0.055 +/- 0.01, n = 66), regardless of the method of theophylline administration or the time of blood sampling. Conversely, this ratio was as low as 0.027 +/- 0.005 in the patient with a long plasma half-life of theophylline. These results suggest that it may be possible to predict the plasma half-life of theophylline for each patient from a single blood sample. This may be useful when planning theophylline administration, especially in patients with abnormal theophylline metabolism.
Adolescent↗
All-trans retinoic acid enhances gap junctional intercellular communication among renal epithelial cells in vitro treated with renal carcinogens.
Epidemiological and clinical studies imply that retinoids have a chemopreventative action against cancer and can suppress the growth of cancer cells. The regulation of connexin (Cx) expression by retinoids varies among tissues and organs. In this study, we investigated whether all-trans retinoic acid (ATRA) upregulates gap junctional intercellular communication (GJIC) in renal epithelial cells exposed to renal carcinogens. Madin Darby canine kidney (MDCK) cells were incubated with ATRA for 3 days, then briefly exposed to 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or renal carcinogens potassium bromate (KBrO3) and dimethylnitrosamine (DMN). ATRA increased the expression of connexin 43 mRNA and protein without affecting Cx 43 phosphorylation and prevented inadequate Cx 43 localisation caused by TPA/KBrO3 or DMN. Consequently, ATRA prevented the disruption of GJIC in MDCK cells. These data suggest that ATRA enhanced GJIC by upregulating Cx 43 expression and that ATRA might be useful for prevention of renal cell carcinoma.
Blotting, Western↗
Value of contrast-enhanced magnetic resonance imaging in differentiation of hemangiomas from lymphangiomas in the oral and maxillofacial region.
OBJECTIVE: The purpose of this study was to investigate the ability of contrast-enhanced magnetic resonance imaging to differentiate hemangioma from lymphangioma in the oral and maxillofacial region. STUDY DESIGN: Contrast-enhanced magnetic resonance imaging was performed in 20 patients (21 masses: 17 hemangiomas and 4 lymphangiomas) through use of either a 0.2-T permanent system or a 0. 5-T superconductive system and spin-echo pulse sequences. RESULTS: After intravenous administration of contrast medium, enhancement was observed in all hemangiomas in areas corresponding to those with high signal on T(2)-weighted images. Unequivocally increased signal was observed in 10 masses, and slightly increased signal was observed in 7 masses. On the other hand, none of the lymphangiomas showed an enhancing mass on contrast-enhanced T(1)-weighted images. CONCLUSIONS: Although contrast-enhanced T(1)-weighted imaging may not improve delineation of masses in all cases, it can be used to differentiate between deep hemangiomas and lymphangiomas.
Adolescent↗
Assessment of image quality in dental radiography, part 1: phantom validity.
OBJECTIVE: The purpose of this study was to describe and validate an image-quality phantom to be used in dental radiography for comparison of film and digitally acquired images. STUDY DESIGN: An aluminum block of 12 steps, with 7 holes in each step, was covered by acrylic blocks. This phantom was radiographed with Kodak Ultra-speed and Ektaspeed Plus films at 70, 65, and 60 kVp with the whole exposure range available. All together, 50 dental films were randomly sequenced and presented to 7 observers. The average number of perceptible holes from all steps was plotted against exposure for each tube voltage and film type, generating a modified perceptibility curve. The tentative optimum exposure level was determined from perceptibility curves in each experimental condition and compared with that determined by means of the standard aluminum stepwedge and the preset time of the x-ray machine. The density range of this phantom at the optimum exposure was compared with that of clinical dental radiographs. Validity of the phantom was evaluated according to the optimum exposure level from the modified perceptibility curves and the overall density range. Finally, the average maximum numbers of perceptible holes at the tentative optimum exposure level were compared for each tube voltage and film type. The statistical test used was a 2-way factorial analysis of variance. RESULTS: The exposure at the perceptibility curve peak approximated that obtained by means of the standard aluminum step-wedge and the time preset by the manufacturer. The overall density range at the perceptibility curve peak covered the clinical density range for each tube voltage and film type. There were no statistically significant differences between film types or among tube voltages. CONCLUSIONS: The x-ray attenuation range for this phantom seemed to approximate clinical conditions. In addition, differences in image quality could be quantitatively evaluated by means of the number of the holes seen in the phantom.
Absorptiometry, Photon↗
Assessment of image quality in dental radiography, part 2: optimum exposure conditions for detection of small mass changes in 6 intraoral radiography systems.
OBJECTIVE: The purpose of this study was to compare 2 film systems and several digital intraoral systems with regard to visual image quality through use of a test phantom developed for this purpose. STUDY DESIGN: The detectors used for digital imaging were as follows: Computed Dental Radiography (CDR), Digora, Dixel, and Sens-A-Ray without scintillator layer. Two types of digital images were prepared for the observer performance test: one with original gray scales and another with contrast enhancement. Images with and without enhancement from the 4 systems were displayed to 7 observers. The change in the average number of perceptible holes was plotted against exposure, and modified perceptibility curves were created and compared with curves for the film systems. The exposure level at which the maximum number of holes was perceived was defined to be optimum. The optimum exposure levels were determined for each digital system and compared with that of the film systems. At the optimum exposure, the average maximum numbers of perceptible holes in each digital system with and without contrast enhancement were compared with the maximum numbers for the film systems. The minimum exposure levels were determined to be those at which the number of perceptible holes exceeded the number for film, and the possibility of exposure reduction was evaluated. RESULTS: All digital systems except the Digora system showed lower optimum exposures than E-speed film. In all digital images without enhancement, however, the maximum number of perceptible holes was significantly lower than that for the film systems at that exposure. With contrast enhancement, all digital systems except the Sens-A-Ray system showed visibility superior to that of the film systems. With the CDR, Digora, and Dixel systems, exposures could be further reduced by a considerable amount, with greater retention of information than was associated with film. CONCLUSIONS: Our results strongly suggest that digital systems, if properly used, can exceed film systems in the detection of small mass changes.
Contrast Media↗
Vascular endothelial growth factor-C expression in human prostatic carcinoma and its relationship to lymph node metastasis.
Lymph node dissemination is a major prognostic factor in human cancer. However, the molecular mechanisms underlying lymph node metastasis are poorly understood. Recently, vascular endothelial growth factor-C (VEGF-C) was identified as a ligand for VEGF receptor-3 (VEGFR-3/Flt-4) and the expression of VEGFR-3 was found to be highly restricted to the lymphatic endothelial cells. In this report, we investigated the expression of VEGF-C and VEGFR-3 in human prostatic carcinoma tissue by using in situ hybridization and immunohistochemical staining respectively. Expression of VEGF-C mRNA in prostatic carcinoma was significantly higher in lymph node-positive group than in lymph node-negative group. In addition, the number of VEGFR-3-positive vessels was increased in stroma surrounding VEGF-C-positive prostatic carcinoma cells. These results suggest that the expression of VEGF-C in prostatic carcinoma cells is implicated in the lymph node metastasis.
Adenocarcinoma↗
Prediction of perceptibility curves of direct digital intraoral radiographic systems.
OBJECTIVES: To derive and test a method to predict Perceptibility Curves (PCs) for direct digital intraoral radiographic systems. METHODS: A test object was used to determine the performance of an average observer with respect to the threshold contrast and internal noise of the human visual system. These data were combined with system parameters to predict PCs mathematically. RESULTS: Data on the performance of an average observer could be defined to obtain values of the effective threshold contrast as a function of background gray level. This function combined with the gamma-value of the system predicted PCs that agreed well with PCs obtained in the conventional way. CONCLUSION: It is possible to predict PCs from a limited number of system parameters together with predetermined data on an average observer.
Artifacts↗
Physical evaluation of a system for direct digital intra-oral radiography based on a charge-coupled device.
OBJECTIVES: To determine technical properties of a direct digital intra-oral radiographic system, the Dixel(R) (J Morita Corporation, Kyoto, Japan). METHODS: A dose response function and the dark current were calculated from two series of exposures to a homogeneous radiation field. The line spread function (LSF) and the modulation transfer function (MTF) were determined from radiographs of an edge. The noise power spectrum (NPS) was determined at three exposures from radiographs exposed to homogeneous radiation fields. Noise equivalent quanta (NEQ) were calculated from the one-dimensional NPS and the MTF. The detective quantum efficiency (DQE) was determined from the NEQ and a representative value of the photon fluence. Signal-to-noise ratios (SNR) were calculated from the NEQs and different signal contrasts. RESULTS: The dose response function demonstrated a slight curvature. There was no effect of the dark current. NPS ranged from 10-5 - 10-7 mm2 depending on exposure and frequency. At a peak of about 2 cycles/mm the DQE is on an average about 30 per cent. SNRs are favorable. CONCLUSION: The technical properties found in this study indicate that the Dixel(R) system is suitable for intra-oral dental radiography.
Artifacts↗
Magnetic resonance imaging of experimentally-induced sialadenitis in rat submandibular glands.
OBJECTIVES: To correlate the features of magnetic resonance (MR) images of experimentally induced obstructive sialadenitis in rat submandibular glands with the histopathological changes. METHODS: Changes in MR images of ligated and non-ligated rat submandibular glands were compared with the histopathological changes and wet weight ratios. Spin echo T1 weighted images (SE T1WI), fast spin echo T2 weighted images (FSE T2WI), and gradient echo T2 weighted images (GE T2WI) were obtained at 1, 2, 3, 4, 5, 7 and 21 days after duct ligation with a 0.3 T MR imaging system. RESULTS: There was a significant difference (P<0.05) between the signal intensity ratios of both ligated and non-ligated glands on each day, except at 21 days on GE T2WI. On SE T1WI, small interval changes of signal intensity ratios were observed on both glands, whereas there were large interval changes at 1 - 2 days, 4 - 7 days and 21 days after duct ligation with FSE T2WI. These three periods correlated highly with three phases of histopathological changes, swelling of acinar cells at 1 - 2 days, atrophy of acinar cells and increase of duct-like structures at 3 - 7 days, and proliferation of connective tissue at 21 days, and the changes in wet weight ratios. A similar tendency was observed on GE T2WI to FSE T2WI. CONCLUSIONS: As FSE T2WI showed large changes in signal intensity that correlated highly with histopathological three phases, it is recommended as the MR sequence of choice for diagnosing the degree of damage in obstructive sialadenitis.
Animals↗
Detection of bone invasion by gingival carcinoma of the mandible: a comparison of intraoral and panoramic radiography and computed tomography.
OBJECTIVE: To assess the diagnostic accuracy of panoramic radiography (PR), panoramic radiography combined with intraoral radiography (PR+IR), and CT in detecting the supero-inferior extent of tumor invasion of the mandible by gingival carcinoma. METHOD: PR, PR+IR, and CT images of the mandible in 37 patients with gingival carcinoma were evaluated by five oral radiologists for the supero-inferior extent of bone invasion using ROC analysis. The mean ROC curve area (Az) of each observer for the different imaging modalities was analysed by nonparametric two-way ANOVA. P<0.05 was considered statistically significant. RESULTS: The mean Az for the detection of bone invasion were 0.88+/-0.03 for PR, 0.77+/-0.12 for PR+IR, and 0.87+/-0.03 for CT (P=0.0907). The mean Az for the detection of bone invasion beyond the alveolus was 0.89+/-0.07 for PR, 0.85+/-0.08 for PR+IR, and 0.83+/-0.06 for CT (P=0.5438). The mean Az for the detection of bone invasion beneath the mandibular canal were 0.94+/-0.04 for PR, 0.94+/-0.02 for PR+IR, and 0.91+/-0. 04 for CT (P=0.2466). No statistically significant differences were observed in Az between PR, PR+IR, and CT. CONCLUSION: We consider that PR+IR should be adopted as the initial imaging modality to determine the extent of supero-inferior invasion of the mandible in gingival carcinoma.
Analysis of Variance↗
Does TUNEL staining during peri- and post-natal development of the mouse inner ear indicate apoptosis?
Terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labelling (TUNEL) is being used more frequently to investigate programmed cell death (PCD). We have applied this method in order to examine how PCD is involved in the development of the mouse inner ear. In a series of studies, we identified a population of TUNEL-positive cells in the perinatal mouse ear that could not be regarded as apoptosis based upon morphological features of the nuclei. Theoretically, TUNEL detects DNA fragmentation, which can also occur in necrosis. Other authors regard TUNEL-positive cells in the sensory epithelia of the rat equilibrium organs between gestational day (GD) 19 and 7 days after birth (DAB) as apoptosis. We determined whether or not cells in the inner ear of perinatal and post-natal mice were TUNEL-positive due to apoptosis. We stained the inner ears of BALB/c mice aged GD17.5-4 weeks by the TUNEL method and analysed morphology by light microscopy and transmission electron microscopy (TEM). TUNEL-positive cells were distinct in the saccule from DAB3, and in the cochlea from DAB8. The number of TUNEL-positive cells in the hair cells of the saccule and in the cochlea increased with age, and seemed to reach a plateau just before 2 weeks of age. However, morphological analyses did not reveal findings characteristic of apoptosis. We conclude that these TUNEL-positive cells were labelled not because of apoptosis, but due to necrosis or post-mortem autolysis. We surmise that TUNEL staining can identify vulnerable cells of the inner ear that consume high levels of oxygen and easily undergo autolysis.
Animals↗