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Biomedical subjects

S Fujieda

Publications and source records attributed to S Fujieda.

At least 19 recordsLinked to original sources
PubMed2001

Granulocyte colony-stimulating factor (G-CSF)-mediated signaling regulates type IV collagenase activity in head and neck cancer cells.

Granulocyte colony-stimulating factor (G-CSF), a hematopoietic cytokine, regulates the proliferation and differentiation of granulocytic progenitor cells and functionally activated mature neutrophils. G-CSF also affects nonhematopoietic tumor cells through its binding to the specific receptor (G-CSFR) on the cells. The type IV collagenase [matrix metalloproteinase 2 (MMP-2)] is known to play a main role in the process of invasion and metastasis, but its regulation, for example, in expression or in activation, is not clearly understood. In this study, we investigated the role of G-CSF in the regulation of tumor cell invasion and the synthesis of MMP-2. G-CSFs producing the head and neck carcinoma cell line T3M-1 cells with metastatic ability and no G-CSF receptor (G-CSFR) expression were transfected with G-CSFR expression vector. In vitro treatment of G-CSFR-transfectant T3M-1 cells with recombinant G-CSF (rG-CSF) significantly augmented their invasive potential in a reconstituted basement membrane (Matrigel) system compared with that of parental cells. Moreover, MMP-2 activity of G-CSFR-transfectant T3M-1 cells was enhanced by the stimulation with rG-CSF, as assessed by gelatin zymography. These results identify G-CSF as a regulator of MMP-2 and cellular invasion.

Carcinoma, Squamous Cell↗
PubMed2001

IL-1 induced chemokine production through the association of Syk with TNF receptor-associated factor-6 in nasal fibroblast lines.

The fibroblasts stimulated by cytokines released the chemokine and recruited the infiltrating cells, including eosinophils, that play a key role in the pathogenesis of airway disease. We established the human fibroblast lines showing high Syk expression and the lines showing low Syk expression from pieces of nasal polyp. IL-1 induces the interaction of TNFR-associated factor (TRAF) 6 with IL-1R-associated kinase, which is rapidly recruited to the IL-1R after IL-1 induction, whereas TRAF2 participates in TNF-alpha-signaling. In the present study, we found that Syk played a different role in IL-1- and TNF-alpha-induced chemokine production through a signaling complex involving Syk and TRAF6. Overexpression of wild-type Syk by gene transfer enhanced RANTES production from nasal fibroblasts stimulated with IL-1. The decrease of Syk expression by the administration of Syk antisense inhibited RANTES production in response to IL-1. However, the change of Syk expression did not affect RANTES production by TNF-alpha stimulation. We concluded that Syk is required for the IL-1-induced chemokine production through the association with TRAF-6 in fibroblasts of nasal polyps.

Cell Line↗
PubMed2001

Protein-tyrosine kinase Syk expressed in human nasal fibroblasts and its effect on RANTES production.

Fibroblasts, a rich source of chemokines, interact with eosinophils and play a key role in the pathogenesis of airway disease. RANTES is produced by fibroblasts to attract and activate eosinophils. LPS is known to induce RANTES and cause protein tyrosine phosphorylation. Nonreceptor protein tyrosine kinase Syk is widely expressed and an important role in intracellular signal transduction in hemopoietic cells. In the present study, we examined whether Syk was expressed in a number of primary human nasal polyp tissue-derived fibroblast lines and whether it played some role in cellular function. Syk proteins were expressed in human nasal fibroblasts, but the expression level varied. There were positive correlations between the level of Syk expression and RANTES production induced by LPS. Overexpression of wild-type Syk by gene transfer enhanced RANTES production from nasal fibroblasts stimulated with LPS. The decrease of Syk expression by the administration of Syk antisense inhibited RANTES production. These results suggest that Syk expression affects RANTES production in fibroblasts of nasal polyps.

Blotting, Western↗
PubMed2001

Effect of gravity field on the nonequilibrium/nonlinear chemical oscillation reactions.

Biological systems have evolved for a long time under the normal gravity. The Belousov-Zhabotinsky (BZ) reaction is a nonlinear chemical system far from the equilibrium that may be considered as a simplified chemical model of the biological systems so as to study the effect of gravity. The reaction solution is comprised of bromate in sulfuric acid as an oxidizing agent, 1,4-cyclohexanedione as an organic substrate, and ferroin as a metal catalyst. Chemical waves in the BZ reaction-diffusion system are visualized as blue and red patterns of ferriin and ferroin, respectively. After an improvement to the tubular reaction vessels in the experimental setup, the traveling velocity of chemical waves in aqueous solutions was measured in time series under normal gravity, microgravity, hyper-gravity, and normal gravity using the free-fall facility of JAMIC (Japan Microgravity Center), Hokkaido, Japan. Chemical patterns were collected as image data via CCD camera and analyzed by the software of NIH image after digitization. The estimated traveling velocity increased with increasing gravity as expected. It was clear experimentally that the traveling velocity of target patterns in reaction diffusion system was influenced by the effect of convection and correlated closely with the gravity field.

Bromates↗
PubMed2001

Expression of granulocyte colony-stimulating factor and its receptor in epithelial skin tumors.

Granulocyte colony-stimulating factor receptors (G-CSFR) have been observed on the surface of not only hematopoietic cells but also several cancer cells. In the present study, we investigated the expression of G-CSFR or G-CSF in epithelial skin tumors by immunohistochemical staining. The assessments were defined by the percentage of G-CSFR or G-CSF positive cells and expressed as G-CSFR and G-CSF scores. The G-CSFR score in SCC (77.6+/-20.0%) was significantly higher than that in Bowen's disease (BD) (51.0+/-35.6%), actinic keratosis (AK) (49.3+/-34.6%) or normal skin (30.0+/-32.1%) (P=0.0004, P=0.0003, P<0.0001, respectively). The mean G-CSF score in SCC (56.7+/-27.4%) or in BD (44.1+/-31.4%) was higher than that in normal skin (24.9+/-25.8%) (P=0.0075, P<0.001, respectively). G-CSF expression in AK (29.8+/-31.2%) was lower than that in SCC (P=0.0037). There was significant positive correlation between the G-CSFR score and the G-CSF score (gamma=0.274, P=0.0107) in skin tumors. These findings suggested that the assessment of G-CSFR expression might be associated with carcinogenesis of skin tumors.

Aged↗
PubMed2001

[Prognostic factors for head and neck cancer].

Smoking, alcohol and chronic stimulation of the teeth are acknowledged as determinants of the risk for head and neck squamous cell carcinoma (H&NSCC) through the loss or mutation of tumor suppressor genes. Despite diagnostic and therapeutic advance, the overall prognosis of H&NSCC remains poor except for laryngeal cancer. Although the prognosis of H&NSCC depends primarily on clinicopathological factors (ex. TNM), the predictive value has been limited for the identification of patients with high risk of disease relapse. Recently, the analysis of DNA, oncogen amplification, and protein expression have been used in attempts to identify a new prognostic indicator for the evaluation and selection of optimal cancer treatment. Here, I review the literature on prognostic factors including chromosomes, cell cycle, apoptosis, angiogenesis, cytokines and adhesion molecules for patients with H&NSCC.

Apoptosis↗
PubMed2001

Appearance of bax protein after preoperative chemoradiotherapy is a prognostic factor in maxillary cancer.

The prognosis for maxillary squamous cell carcinoma (SCC) remains poor, despite advances in combination therapy. Combined treatment with anticancer drugs and radiation therapy is aimed at inducing apoptosis. As apoptosis is regulated by several proteins, we investigated the expression of p53, Bax and Bcl-2 in maxillary SCC before treatment and after preoperative chemoradiotherapy using an immunohistochemical approach. Furthermore, apoptotic cells were visualized using an in situ apoptosis detection kit and the apoptosis index (AI) was defined as the number of positive cancer cells per 1,000 cancer cells. Expression of p53 and Bcl-2 and the Al in 23 maxillary SCCs were not associated with tumor size, lymph node metastasis, clinical stage, frequency of recurrence or 5-year survival rate either before treatment or after preoperative chemoradiotherapy. Bax expression before treatment was not correlated with any clinicopathological factors before treatment. However, no patients in the Bax-positive group (11/22 cases) after preoperative chemoradiotherapy had recurrence of maxillary SCC and all were alive after 5 years, while the 5-year survival rate was 34.1% in Bax-negative patients. These results suggest that the appearance of the Bax protein after preoperative chemoradiotherapy is a significant prognostic marker for maxillary SCC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Expression of fas (CD95) ligand is correlated with IL-10 and granulocyte colony-stimulating factor expression in oral and oropharyngeal squamous cell carcinoma.

The Fas/Fas ligand (FasL) pathway has been shown to be an important cellular pathway mediating apoptosis. In this study we investigated the expression of Fas and FasL and the rate of spontaneous apoptosis in 58 oral and oropharyngeal squamous cell carcinoma (SCC) by using immunohistochemical techniques. There was no correlation between Fas or FasL expression and clinicopathological factors. The expression of Fas in the tumor did not affect spontaneous apoptosis of the tumor cells. However, FasL expression was associated with IL-10 and granulocyte colony-stimulating factor expression in oral and oropharyngeal SCC. These results suggested that the Fas/FasL system is connected with the expression of various factors including cytokines in tumor cells.

Aged↗
PubMed2000

Intractable pediatric chronic sinusitis with antrochoanal polyp.

It has been reported that pediatric chronic sinusitis with antrochoanal polyp is difficult to cure because it tends to recur easily even with surgery. Therefore, in order to improve its cure rate, aggressive treatment combining polypectomy, intra-maxillary intubation through the inferior meatus, macrolide administration, etc., was attempted. Thirty-seven sides of pediatric chronic sinusitis with antrochoanal polyp and 44 sides of chronic sinusitis without polyp were evaluated after the same treatments. The mean age of patients was 9.7 years, and the mean intubation period was 20 months. Since subjective improvements in children are questionable, the efficacy was evaluated strictly on the basis of X-ray alone focusing on the maxillary sinus. Twenty-four percent of the group with antrochoanal polyp showed 'excellent' effect, i.e. almost complete resolution of the sinus findings, while 45% of the group without polyp showed 'excellent' effect, with a mean follow-up period of 3 years and 6 months. This difference was significant (P<0. 01, chi(2)-test). These results further document the intractableness of chronic sinusitis with choanal polyp in children.

Adolescent↗
PubMed2000

Conventional tumor markers are prognostic indicators in patients with head and neck squamous cell carcinoma.

We tested for squamous cell carcinoma-related antigen (SCC), carcinoembryonic antigen (CEA), ferritin, immunosuppressive acid protein (IAP) and sialic acid in the serum from 247 patients with head and neck squamous cell carcinoma prior to therapy. Significant correlations were found between IAP and tumor size, lymph node metastasis, and clinical stage (P<0.0001, P<0.001, and P<0.0001). Also, sialic acid and SCC were also correlated with tumor size, lymph node metastasis, and clinical stage. Moreover IAP, sialic acid and SCC were strongly associated with survival rate (P<0.0001, P = 0.0230 and P = 0.0159). A multivariate Cox proportional hazard model demonstrated that being positive for IAP was an independent predictor for patients with H&NSCC (P = 0.0115). The results indicate that IAP, sialic acid and SCC are useful as prognostic factors.

Antigens, Neoplasm↗
PubMed2000

Induction of IgA against Haemophilus parainfluenzae antigens in tonsillar mononuclear cells from patients with IgA nephropathy.

Much evidence suggests that IgA production in vivo and in vitro is enhanced in patients with IgA nephropathy (IgAN). We have demonstrated glomerular deposition of the outer membranes of Haemophilus parainfluenzae (HP) antigens (OMHP) and the presence of HP-specific IgA in the serum of patients with IgAN. In this study, we investigated the production of IgA and several cytokines by tonsillar mononuclear cells (TMC) from IgAN patients induced by stimulation with OMHP. The spontaneous production of total IgA and TGF-beta by TMC from IgAN patients was higher than that by TMC from patients with chronic tonsillitis (CT) (P < 0.05). Stimulation with OMHP in vitro enhanced the production of HP-specific IgA by TMC from IgAN patients (P < 0.01), but not by TMC from CT patients. OMHP stimulation also enhanced the production of TGF-beta and IL-10 by TMC from IgAN patients (P < 0.001). These results suggest that the infection of HP in the tonsil may be involved in the etiology of IgAN.

Adolescent↗
PubMed2000

Expression of platelet-derived endothelial cell growth factor and vascularity in the nasal mucosa from allergic rhinitis.

BACKGROUND: Angiogenesis plays critical roles in various pathological mechanisms. It has been hypothesized that the vascularity in allergic nasal mucosa is different from that in normal mucosa, and that changes in the vascular network contributes the pathogenesis of allergic rhinitis. OBJECTIVE: To determine whether hypervascularity and overexpression of the platelet-derived endothelial cell growth factor (PD-ECGF), an angiogenic factor, are found in allergic nasal mucosa and whether these two factors are associated with the allergic reaction. METHODS: We investigated the expression of PD-ECGF and counted microvessels in 51 nasal mucosae (30 samples from patients with allergic rhinitis and 21 samples as control from normal subjects) using an immunohistochemical technique. RESULTS: PD-ECGF expression in allergic nasal mucosae was significantly higher than that in control mucosae at the interstitium of the lamina propria (P = 0.0024) and nasal gland (P = 0.024). PD-ECGF positive areas were coincident with areas of high vascularity in the sections. The microvessel count in the lamina propria of allergic mucosae was higher than that of control mucosae (P = 0.050). Regarding the correlation with various clinical factors, the total nasal symptom score was significantly associated with both the PD-ECGF expression in the interstitium of the lamina propria (P < 0.05) and in the nasal gland (P < 0.005), as well as with the number of vessels (P < 0.05). CONCLUSION: PD-ECGF and hypervascularity in the nasal mucosa may be involved in the pathogenesis of allergic rhinitis.

Blood Platelets↗
PubMed2000

Immune response of tonsillar lymphocytes to Haemophilus parainfluenzae in patients with IgA nephropathy.

The pathogenesis of IgA nephropathy (IgAN) is unclear. We have previously shown glomerular deposition of Haemophilus parainfluenzae (HPI) antigens and the presence of IgA antibody against HPI antigens in patients with IgAN. We examined the immune response to HPI antigens in tonsillar lymphocytes from patients with IgAN. Lymphocytes isolated from the palatine tonsils of 13 IgAN patients and 16 patients with chronic tonsillitis but without renal disease were used as controls. We examined lymphocyte proliferation and production of IgA antibody against HPI antigens by measuring thymidine uptake and IgA antibody in culture supernatants after lymphocyte incubation with HPI antigens. Patients with IgAN showed a significantly higher stimulation index to HPI antigens (thymidine incorporation in tonsillar lymphocytes with HPI/thymidine incorporation in unstimulated tonsillar lymphocytes) than controls (P < 0.002). Lymphocytes from patients with IgAN also showed a significantly higher level of IgA antibody and IgA1 antibody against HPI antigens in culture supernatants than lymphocytes from controls (P = 0.0002 and P = 0.004, respectively). Our results suggest that HPI antigens stimulate tonsillar T and B lymphocytes in patients with IgAN and that an immune response to HPI antigens may play a role in the pathogenesis of this disease in some cases.

Adolescent↗
PubMed2000

Eosinophilic apoptosis in sinus mucosa: relationship to tissue eosinophilia and its resolution in allergic sinusitis.

BACKGROUND: Apoptosis, which is regulated by both cell survival and death signals, is important for the swift clearance of unwanted cells. OBJECTIVE: We sought to elucidate whether eosinophilic apoptosis is associated with tissue eosinophilia and to determine its resolution in allergic sinusitis (AS). METHODS: Numbers of eosinophils, numbers of IL-5(+) cells, and the apoptosis index of eosinophils were calculated in the submucosa (both superficial and deep layers) of patients with AS by using histochemical methods before and after prednisolone treatment. Patients without AS were used for control groups. Anti-EG2 antibody was used to identify eosinophils. IL-5, Fas, or Bax expression of eosinophils was evaluated to elucidate the role of the factors affecting eosinophilic apoptosis. RESULTS: EG2 and IL-5(+) cells were abundant in the submucosa of patients with AS, especially in the superficial layer. About 50% to 60% of the IL-5-producing cells were eosinophils. Apoptotic eosinophils were less numerous in the superficial layer than the deep layer in these diseases. After prednisolone treatment, an induction of eosinophilic apoptosis was accompanied by a significant decrease in the number of EG2(+) and IL-5(+) cells. No remarkable difference was observed in the Fas or Bax expression of eosinophils after prednisolone treatment. CONCLUSION: Autocrine secretion of IL-5 from eosinophils may be one reason why eosinophilic disease is difficult to manage. Induction of eosinophilic apoptosis is critical for reversing tissue eosinophilia in patients with AS.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Production of interferon-gamma by tonsillar mononuclear cells in IgA nephropathy patients.

Much evidence, both in vivo and in vitro, suggests that patients with IgA nephropathy (IgAN) have enhanced IgA production. We hypothesized that Haemophilus parainfluenzae (HP) in the tonsil plays an important role in the IgA production of IgAN patients. In this study, we focused on interferon-gamma (IFN-gamma) and IgA production by tonsillar mononuclear cells (TMC) in patients with IgAN. Tonsillectomies were performed in patients with IgAN and chronic tonsillitis (CT). The induction of IFN-gamma and IgA in vitro by TMC from IgAN patients was compared with that from CT patients. In addition, we investigated whether stimulation with the outer membranes of HP (OMHP) enhanced IFN-gamma and IgA induction by TMC from patients with IgAN. Spontaneous IFN-gamma production and spontaneous total IgA production by TMC were higher in IgAN patients than in those patients with CT (p < 0.05). IFN-gamma induction by OMHP stimulation was also higher in IgAN patients than in CT patients. The stimulation of OMHP enhanced HP-specific IgA in IgAN but had no influence on the production of IFN-gamma in patients with either IgAN or CT compared with spontaneous IFN-gamma production. IFN-gamma production was positively correlated with total IgA values in both IgAN and CT patients, but not with HP-specific IgA. These results suggest that increased IFN-gamma production in patients with IgAN is not associated with HP infection but may play a role in the pathogenesis of IgAN.

Adenoids↗
PubMed2000

Synthesis of immunoglobulins against Haemophilus parainfluenzae by tonsillar lymphocytes from patients with IgA nephropathy.

BACKGROUND: We previously demonstrated glomerular deposition of Haemophilus parainfluenzae (HP) antigens and the presence of IgA antibody against HP antigens in patients with IgA nephropathy (IgAN). In this report we examine the synthesis of immunoglobulins against HP antigens in tonsillar lymphocytes from patients with IgAN. METHODS: We used tonsillar lymphocytes isolated from the palatine tonsils of 15 patients with IgAN and 16 patients with chronic tonsillitis but without renal disease. We examined lymphocyte proliferation and production of IgA, IgG, and IgM antibodies against HP antigens by measuring thymidine uptake and concentrations of these antibodies in culture supernatants after lymphocyte incubation with HP antigens by ELISA. RESULTS: Lymphocytes from patients with IgAN showed a significantly higher stimulation index (SI) on exposure to HP antigens (thymidine incorporation in tonsillar lymphocytes exposed to HP (c.p.m.)/ thymidine incorporation in unstimulated tonsillar lymphocytes (c.p.m.)) than did controls (P=0. 0015). Lymphocytes from patients with IgAN also showed a significantly higher IgA SI (concentrations of IgA against HP antigens in supernatants from HP-stimulated lymphocytes/IgA against HP antigens in supernatants from unstimulated tonsillar lymphocytes) than did controls (P=0.0004). We found positive correlations between concentrations of IgA and IgG antibodies, between IgA and IgM antibodies, and between IgG and IgM antibodies against HP antigens after HP stimulation. CONCLUSIONS: Our results suggest that HP antigens stimulate tonsillar T and B lymphocytes in patients with IgAN and that these patients have polyclonal activation of lymphocytes against HP antigens, with isotype switching of antibody production from IgM to IgA.

Adolescent↗
PubMed2000

Synthetic oligodeoxynucleotides inhibit IgE induction in human lymphocytes.

Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs have the capacity to stimulate T-helper (Th)1-type responses in mice. Th1 cytokines are known to act as downregulators of IgE production. In this study we investigated whether synthetic ODNs inhibited IgE production in human peripheral blood mononuclear cells (PBMC) from normal donors stimulated with interleukin (IL)-4 plus anti-CD40 monoclonal antibody (mAb) in vitro. Thirty-mer single-stranded ODNs were randomly selected from the complementary DNA encoding the MPB-70 of Mycobacterium bovis Bacillus Calmette-Guerin. Two ODNs, containing CGTACG or AACGTT inhibited IgE production by human PBMC. When other oligonucleotides were substituted in a portion of the sequence of the core or flanking oligonucleotides in the ODN containing CGTACG, ODNs containing NACGTTCG or A/CTCGTTCG sequences specifically inhibited IgE production by human PBMC in vitro. The inhibition of IgE production by certain ODNs was mediated by both interferon (IFN)-gamma and IL-12, since the ODN-induced suppression was blocked by the addition of anti-IFN-gamma or anti-IL-12 mAb. Also, the ODNs inhibited induction of epsilon germline transcripts by IL-4. Our findings indicate that synthetic ODNs appear to be candidates for the treatment of IgE-dependent allergic disease in humans.

Animals↗