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Biomedical subjects

Hideki Fujita

Publications and source records attributed to Hideki Fujita.

At least 19 recordsLinked to original sources
PubMed2006

Psychophysical evaluation of calibration curve for diagnostic LCD monitor.

PURPOSE: In 1998, Digital Imaging Communications in Medicine (DICOM) proposed a calibration tool, the grayscale standard display function (GSDF), to obtain output consistency of radiographs. To our knowledge, there have been no previous reports of investigating the relation between perceptual linearity and detectability on a calibration curve. MATERIALS AND METHODS: To determine a suitable calibration curve for diagnostic liquid crystal display (LCD) monitors, the GSDF and Commission Internationale de l'Eclairage (CIE) curves were compared using psychophysical gradient delta and receiver operating characteristic (ROC) analysis for clinical images. RESULTS: We succeeded in expressing visually recognized contrast directly using delta instead of the just noticeable difference (JND) index of the DICOM standard. As a result, we found that the visually recognized contrast at low luminance areas on the LCD monitor calibrated by the CIE curve is higher than that calibrated by the GSDF curve. On the ROC analysis, there was no significant difference in tumor detectability between GSDF and CIE curves for clinical thoracic images. However, the area parameter Az of the CIE curve is superior to that of the GSDF curve. The detectability of tumor shadows in the thoracic region on clinical images using the CIE curve was superior to that using the GSDF curve owing to the high absolute value of delta in the low luminance range. CONCLUSION: We conclude that the CIE curve is the most suitable tool for calibrating diagnostic LCD monitors, rather than the GSDF curve.

Calibration↗
PubMed2006

Genome-wide screening of dioxin-responsive genes in fetal brain: bioinformatic and experimental approaches.

Many of the effects of dioxins, which are potent environmental pollutants and teratogens, are mediated through the aryl hydrocarbon receptor, also known as the dioxin receptor. The purpose of the present study was to characterize dioxin-responsive genes in a comprehensive manner using two complementary approaches: bioinformatic analysis and microarray analysis. First, we characterized the overall distribution of the cis-regulatory element for the dioxin-responsive element sequence (DRE) 'gcgtg' within putative promoter regions. We assembled the upstream sequences 10 kb from the transcription start site and evaluated their location and frequency in the human and mouse genomes. Second, we characterized the expression profile of mouse embryonic day 12 fetal brain exposed to 2,3,7,8-tetrarchlorodibenzo-p-dioxin. The distributions of 26,680 DREs among 2,843 human genes and 98,711 DREs among 18,541 mouse genes were examined. In both species, the DREs tended to be located close to the transcription start site. Forty genes exhibited significant induction or repression following dioxin exposure in fetal mice. The set of genes exhibited a strong functional coherence, with statistically significant enrichment in organogenesis and the DNA-dependent regulation of transcription, according to Gene Ontology annotations. In both humans and mice, DREs were preferentially distributed close to transcription start sites. Evolutionary conservation of this unique DRE distribution pattern suggests that DREs may be involved in transcriptional regulation. In mice, prenatal dioxin exposure altered the expression of 10 transcription factors, many of which have been documented to play a role in organogenesis. These genes may represent potential mediators of dioxin's effects in fetal tissues.

Animals↗
PubMed2005

Signaling through CD40 ligand decreases CD80 expression on murine Langerhans cells and enhances IL-12 p40 production.

We previously showed that murine Langerhans cells (LC) express CD40 ligand (CD40L). In this study, we further investigated the function of CD40L on LC using agonistic antibodies and CD40L knockout (KO) mice. Signaling through CD40L decreased CD80 expression on LC 48 h after stimulation and the decrease was more remarkable in the presence of interferon-gamma (IFN-gamma). Signaling through CD40 enhanced the production of IL-12 p40 from LC, and simultaneous signaling through CD40L slightly augmented this effect. Addition of IFN-gamma further enhanced IL-12 p40 production. LC from CD40L KO mice expressed similar levels of surface molecules such as CD40, CD80, CD86, and MHC class II, compared with those from wild-type mice. However, they produced less amount of IL-12 p40 during 48 h after purification. These results suggest that signaling through CD40L on LC is important in regulating IL-12 production, which is critical for Th1 type immune responses.

Animals↗
PubMed2005

Differential production of Th1- and Th2-type chemokines by mouse Langerhans cells and splenic dendritic cells.

Some chemokines specifically attract T helper 1 (Th1) cells, whereas others attract T helper 2 (Th2) cells. In this study, we investigated the capacity of Langerhans cells (LC) to produce Th1- and Th2-type chemokines in comparison with that of splenic CD11c(+) dendritic cells (DC). We prepared highly purified (>95%) LC from BALB/c mouse skin using the panning method. With regard to Th1-type chemokines, exogenous stimulus, such as interferon-gamma (IFN-gamma), lipopolysaccharide, or polyinosinic-polycytidylic acid, was mandatory for the production of substantial amounts of CXCL10, CXCL9, and CXCL11 both in LC and splenic DC. LC, as a whole, exhibited low ability to produce Th1-type chemokines in comparison with splenic DC. As for Th2-type chemokines, LC, but not splenic DC, produced high levels of CCL22 and CCL17 constitutively during culture even without exogenous stimuli. The production of Th2-type chemokines was regulated in a complicated manner. In particular, interleukin-4 upregulated, and IFN-gamma downregulated both CCL22 and CCL17 production by LC. Of note, LC produced much more amounts of Th2-type chemokines than splenic DC under any conditions tested. Finally, Th1- and Th2-type chemokines produced by LC were shown to be functional using chemokine receptor-transfected-2B4 T cells. The high production of CC chemokine receptor 4 ligands by LC in the absence of IFN-gamma may be an important character discriminating LC from other DC.

Animals↗
PubMed2005

Type I interferons inhibit maturation and activation of mouse Langerhans cells.

Type I interferons (IFN) have an essential role in antiviral defense, and they are produced upon viral infection in a variety of cells. IFN-alpha/beta treatment of immature dendritic cells (DC) is known to induce their phenotypic and functional maturation, but it remains unclear whether stimulation by this cytokine family influences the functions and maturation of Langerhans cells (LC). We used highly enriched (>95%) LC directly isolated from BALB/c mouse skin and addressed this issue, comparing LC with splenic CD11c(+) DC. Type I IFN-treated LC exhibited impaired ability to produce IL-12 and inflammatory cytokines, IL-6 and TNF-alpha, whereas IL-10 production was not augmented. In splenic DC, the production of inflammatory cytokines was rather enhanced by type I IFN treatment. With regard to chemokines, in both LC and splenic DC, type I IFN upregulated the production of inflammatory chemokines, such as CXCL10, CXCL11, CCL3, CCL4, and CCL5. Strikingly, IFN-beta treatment reduced the expression of CD40, CD54, CD80, and CD86 on LC, whereas IFN-beta-treated splenic DC showed enhanced expression of these molecules. Furthermore, IFN-beta-treated LC had impaired costimulatory activity for anti-CD3-induced proliferation of T cells. Finally, treatment with IFN-alpha/beta reduced the migratory capacity of LC to CCL21. These results indicate that type I IFN inhibit maturation and activation of LC in a direct manner. Our observations may provide a novel explanation for the reported inability of LC to act as potent antigen-presenting cells in cutaneous and mucosal viral infection.

Animals↗
PubMed2005

Mycosis fungoides associated with intestinal mucosa-associated lymphoid tissue lymphoma.

Coexistence of cutaneous T-cell lymphoma (CTCL) and a B-cell malignancy is rare. We report a case of mycosis fungoides (MF) associated with intestinal mucosa-associated lymphoid tissue (MALT) lymphoma, which is a low-grade B-cell lymphoma of marginal cell origin. To the best of our knowledge, there have been only two cases of coexistent CTCL and MALT lymphoma, and this is the first case with typical MF and intestinal MALT lymphoma. The coexistence in our case might be coincidental, but genetic predisposition and the immunoregulatory capacity of neoplastic T lymphocytes may be factors contributing to this association.

Antigens, CD20↗
PubMed2005

Verification imaging using a computed radiography system for high-energy electron beam therapy.

PURPOSE: The aim of this study was to examine a method to more conveniently acquire verification images. A computed radiography (CR) system was employed using a photostimulable phosphor plate and diagnostic cassette used for taking diagnostic X-ray photographs. MATERIALS AND METHODS: Verification images were acquired using the diagnostic cassette and therapy cassette. Image processing parameters were adjusted to improve the image quality. Verification images were printed using optimum parameters, and 10 radiation technicians visually evaluated the images. The sign test was used, and image quality was evaluated using a two-sided test at a 5% level of significance. To assess its clinical value, a radiation oncologist evaluated patient verification images. RESULTS: Verification image quality was improved by the adjustment of image processing parameters. As a result of the image quality evaluation, there were no significant differences between the two types of cassette (p>0.05). In most of the clinical cases (98%), the verification images were useful. CONCLUSION: We found that good quality verification images were acquired by a CR system with a diagnostic cassette. This system is suitable for practical use to acquire daily verification images, and it is considered useful for maintaining quality assurance (QA) in high-energy electron beam therapy.

Humans↗
PubMed2004

Langerhans cells exhibit low responsiveness to double-stranded RNA.

Double-stranded RNA (dsRNA) is a viral product recognized by Toll-like receptor 3 (TLR3), and it is a potent activator of dendritic cells (DC). We compared Langerhans cells (LC) and splenic CD11c(+) DC and investigated the responsiveness to dsRNA. We prepared highly purified LC (> 95%) using the panning method. TLR3 mRNA was expressed in LC, splenic DC, and keratinocytes (KC). The expression of IFN-beta mRNA was enhanced in LC and splenic DC by Poly(I:C) stimulation. However, cytokine/chemokine production in response to Poly(I:C) by LC was much lower than that by splenic DC. In addition, Poly(I:C) induced further maturation in splenic DC, but not in LC. Finally, we found that the mouse KC cell line, PAM212, produced a great amount of IL-1alpha by Poly(I:C) stimulation, and that IL-1alpha promoted the maturation of LC. These data altogether indicate that LC exhibit low responsiveness to dsRNA. It is possible that KC may primarily trigger anti-viral immune responses in the skin via cytokine production such as IL-1alpha.

Animals↗
PubMed2004

Differential effects of LPS and TGF-beta on the production of IL-6 and IL-12 by Langerhans cells, splenic dendritic cells, and macrophages.

We examined modulatory effects of lipopolysaccharide (LPS) on IL-6 and IL-12 production by mouse Langerhans cells (LC), spleen-derived CD11c+ dendritic cells (DC), and macrophages (Mphi). Low dose LPS (1 ng/ml) increased IL-6 and IL-12 p40 production by Mphi. LPS slightly augmented IL-6 production but showed no effect on IL-12 p40 production by DC. In contrast, only high dose LPS (1 microg/ml) induced IL-6 but not IL-12 p40 production by LC. CD14 expression was the highest on Mphi and then on DC, but not on LC, which may explain the difference in responsiveness to LPS. We also found that TGF-beta inhibited IL-6 and IL-12 p40 production by LPS-stimulated Mphi. However, TGF-beta did not inhibit IL-6 production and even enhanced IL-12 p40 production by anti-CD40/IFN-gamma-stimulated Mphi. Concerning LC, TGF-beta enhanced IL-6 and IL-12 p40 production when stimulated with anti-CD40/IFN-gamma alone or with anti-CD40/IFN-gamma and LPS. Taken together, these findings indicate diverse effects of LPS and TGF-beta on these antigen presenting cells, which probably represents their differential roles in the innate immunity.

Animals↗
PubMed2004

Differential expression and function of Toll-like receptors in Langerhans cells: comparison with splenic dendritic cells.

Toll-like receptors are key elements in pathogen recognition by the host immune system. Although the expression pattern and functions of Toll-like receptors have been studied in a variety of cytokine-induced dendritic cells, it remains unknown whether Toll-like receptor stimulation influences maturation and cytokine production of authentic Langerhans cells. We purified murine epidermal Langerhans cells along with splenic dendritic cell using a panning method. Langerhans cells expressed Toll-like receptor 2, 4, and 9 but not 7, the pattern of which suggests Langerhans cells are the closest to one of the murine dendritic cell lineage, CD11c+11b+8 alpha-4-. Then we stimulated Toll-like receptor 2, 4, and 9 with the corresponding ligand, Staphylococcus aureus Cowan 1, lipopolysaccharide, and CpG, and found that all of these stimuli upregulated expression of B7-1 and B7-2 in splenic dendritic cells but not in Langerhans cells. As in human Langerhans cells, stimulation of murine Langerhans cells with Staphylococcus aureus Cowan 1, lipopolysaccharide, and CpG overall resulted in T helper 1-polarizing cytokine production (namely, induction of IL-12p40 and inhibition of TARC (thymus and activation-regulated chemokine)/CCL17). Exceptionally, lipopolysaccharide exhibited no effect on IL-12p40 production by Langerhans cells and inhibited IL-12p40 production by splenic dendritic cells. These results may represent the functional heterogeneity between Langerhans cells and splenic dendritic cells, and are important for better understanding of innate immunity to bacterial infections differentially regulated in the skin and spleen. MeSH terms: Toll-like receptors, Langerhans cells, dendritic cells.

Animals↗
PubMed2004

Lack of association of CCR4 single nucleotide polymorphism with atopic dermatitis in Japanese patients.

CCR4, a member of the CC chemokine receptor family, is believed to play an important role in the pathogenesis of atopic dermatitis. To examine whether CCR4 single nucleotide polymorphism (SNP) is associated with susceptibility to atopic dermatitis, we investigated the allele and genotype frequencies of C1014T SNP of CCR4 in 198 Japanese patients with atopic dermatitis and controls by a PCR-restriction fragment length polymorphism method. There was no significant difference in allele or genotype frequencies between patients with atopic dermatitis and controls. Serum IgE levels and peripheral blood eosinophil counts were not significantly different among genotypes. There was also no significant difference in allele or genotype frequencies between the patient subgroup with and without asthma, with mild or moderate disease, with and without family history of atopic dermatitis, or with and without family history of atopic disorders. C1014T SNP of CCR4 does not appear to be associated with susceptibility to atopic dermatitis in Japanese patients.

Adolescent↗
PubMed2004

The -431C>T polymorphism of thymus and activation-regulated chemokine increases the promoter activity but is not associated with susceptibility to atopic dermatitis in Japanese patients.

BACKGROUND: Thymus and activation-regulated chemokine (TARC) plays an important role in the pathogenesis of atopic dermatitis (AD). We recently detected the single nucleotide polymorphism (SNP) (-431C>T) in the 5'-flanking region of TARC gene. OBJECTIVES: To examine whether the -431C>T SNP of the TARC gene is associated with susceptibility to AD and whether it affects the promoter activity of the TARC gene. METHODS: We investigated the genotype and allele frequencies of the SNP in 193 AD patients and 158 healthy controls by polymerase chain reaction-restriction fragment length polymorphism method. We compared the promoter activities between TARC promoter carrying 431C and that carrying -431T by transient-transfection assay in DJM-1 cell line. RESULTS: There were no significant differences in genotype or allele frequencies between AD patients and controls (genotype: P = 0.38, allele: P = 0.22). Luciferase activity was higher in -431T constructs than in -431C constructs (2.3-fold, P = 9.5 x 10(-6)). CONCLUSION: These results suggest that the -431C>T SNP of the TARC gene enhances the promoter activity of TARC gene but is not associated with susceptibility to AD in Japanese population.

Adolescent↗