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S Fujieda

Publications and source records attributed to S Fujieda.

At least 55 records · Page 3Linked to original sources
PubMed1998

CD1-restricted T-cells influence IgG subclass and IgE production.

BACKGROUND: Human CD1 has recently emerged as a third family of antigen-presenting molecules that is distinct from either major histocompatibility complex class I or class II. OBJECTIVE: We investigated whether the CD1b-restricted T-cell interaction with antigen alters human IgG subclass and IgE isotype production. METHODS: CD1b-restricted antigen-specific T cells derived from the skin lesion of a patient with leprosy were stimulated with their cognate antigen, lipoarabinomman (LAM) of Mycobacterium leprae, in the presence of CD1+ antigen-presenting cells and tested for their ability to alter IgG subclass and IgE production from IgD+ B cells. RESULTS: CD1-restricted T cells cultured with CD1+ antigen-presenting cells in the absence of LAM induced IgG1, IgG3, IgG4, and IgE, whereas CD1b-restricted T cells cultured in the presence of LAM induced IgG1 and IgG3 and inhibited production of IgG4 and IgE. Production of IgG4 and IgE was rescued in the CD1-restricted system by the addition of anti-interferon-gamma. IgG2 production was not induced under any circumstances. CONCLUSION: In this study we demonstrated that a specific CD1b-restricted T-cell line can behave similarly to classically-restricted Th1-type T cells. CD1b-restricted T-cells of this type may regulate immune responses to microbial pathogens by simultaneously enhancing cell-mediated immunity and downregulating IgG4 and IgE responses.

Antigen-Presenting Cells↗
PubMed1998

Combined nasal challenge with diesel exhaust particles and allergen induces In vivo IgE isotype switching.

In this study we undertook to provide evidence for local in vivo isotype switching to IgE following nasal challenges. Detection of deleted switch circular DNA (switch circles) by a novel nested polymerase chain reaction-based approach was employed as definitive molecular evidence of Ig isotype switching. Nasal challenge in humans with diesel exhaust particles (DEP) plus ragweed antigen has been shown to enhance local IgE production, stimulate local cytokine production, and markedly increase mucosal IgE antibody to ragweed. Four days after combined intranasal DEP plus ragweed challenge, we detected and characterized clones of deleted switch circular DNA (Sepsilon /Smu) representing switching from mu to epsilon from nasal lavage cells. No switch circular DNA was detected in nasal lavage cells following challenge with DEP alone nor with ragweed allergen alone. These results indicate that the combination of mucosal stimulation with DEP and ragweed allergen is capable of driving in vivo isotype switching to IgE in humans with ragweed allergy. These results are the first direct demonstration of in vivo IgE isotype switching in humans.

Adult↗
PubMed1998

CD40 stimulation inhibits cell growth and Fas-mediated apoptosis in a thyroid cancer cell line.

CD40 plays a critical role in the humoral immune response, especially in B-cell proliferation, differentiation, production of antibody, secretion of cytokines, and apoptosis. Here, we examined CD40 expression on six head and neck cancer cell lines by flow cytometry. Only the HTC/C3 cell line, which originated from a thyroid cancer, expressed CD40 on the surface of the cells. Coculture with anti-CD40 mAb inhibited colony formation of HTC/C3 cells. CD40 stimulation enhanced Fas expression on HTC/C3 cells. Although HTC/C3 cells are sensitive to Fas-mediated apoptosis, CD40 stimulation inhibited Fas-mediated apoptosis in HTC/C3 cells. CD40 stimulation enhanced Bcl-2 expression, and antisense oligonucleotide against bcl-2 canceled the inhibition of HTC/C3 cell growth caused by CD40 stimulation. Additionally, more anti-CD40 mAb-treated HTC/C3 cells were accumulated in G1 phase, and fewer in S phase, compared to nontreated cells. These results suggest that CD40 stimulation might be involved in the slow growth rate of CD40-bearing cancer cells, and they suggest a new biological approach to the treatment of cancers.

Antibodies, Monoclonal↗
PubMed1998

Expression of platelet-derived endothelial cell growth factor in oral and oropharyngeal carcinoma.

Platelet-derived endothelial cell growth factor (PD-ECGF) was isolated as an endothelial cell mitogen from platelets. In this study, we investigated the expression of PD-ECGF and counted microvessels in 58 oral and oropharyngeal squamous cell carcinoma (SCC) specimens by an immunohistochemical technique to examine their prognostic significance and performed tumor in vitro sensitivity to 5-fluorouracil (5-FU) and cisplatin as determined by a bioluminescence assay of the ATP values of tumor cells after continuous exposure. The percentage of PD-ECGF-positive tumor cells (PD-ECGF score) was correlated with the frequency of the recurrence of disease (P=0.0043) but not with sex, tumor size, metastasis, or clinical stage. Overall survival of the high PD-ECGF expression group (>40% PD-ECGF score) was shorter than the low expression (<40%) group (P=0.0365). Vessel count was correlated with lymph node metastasis and clinical stage. The survival of patients with hypervascularity (more than the median of intratumor vessel counts, >82) was shorter than that of those with hypovascularity (vessel count <81, P=0.0446). However, there was no association between PD-ECGF expression and vessel count. Cox proportional multivariate analysis showed that PD-ECGF expression was the most significant independent prognostic indicator for overall survival. The susceptibility to 5-FU cytotoxicity in the extremely high PD-ECGF expression groups (>70% of PD-ECGF score) was significantly higher than that in the low group, whereas there was no difference in their sensitivity to cisplatin. These results showed that carcinoma cells with high PD-ECGF expression were sensitive to 5-FU in spite of poor prognosis. These data provide further information when deciding on adjuvant therapy for oral and oropharyngeal SCCs.

Analysis of Variance↗
PubMed1996

Multiple types of chimeric germ-line Ig heavy chain transcripts in human B cells: evidence for trans-splicing of human Ig RNA.

Germ-line transcripts from Ig heavy chain loci precede the occurrence of isotype switching and are thought to play an important though still controversial role in Ig class switching. In this study, we employed a reverse transcriptase-PCR approach to detect human chimeric Ig germ-line mRNA transcripts. Multiple types of chimeric Ig germ-line transcripts (Imu-Cepsilon, Iepsilon-Cmu, Imu-Cgamma4, Igamma-Cmu, Igamma-Cepsilon, Iepsilon-Cgamma, and Igamma4-Calpha1 transcripts) were readily detected in human B cells stimulated with IL-4 alone. Sequence analysis revealed that all of these chimeric Ig germ-line transcripts represented the I exons from one Ig locus spliced to the CH exons from another locus by using consensus sequences for splicing donor and acceptor sites, indicating that they were generated through splicing machinery. In the case of stimulation of human resting B cells with IL-4 alone, the chimeric Ig germ-line transcripts are likely derived from a trans-splicing mechanism, as the extensive searching did not find evidence that Ig class-switch recombination had occurred, which alternatively could give rise to chimeric Ig mRNA by mechanisms other than trans-splicing. Similarly, an EBV-transformed gamma2 rearranged B cell line, GM1500, which produces IgG2 and contains both gamma2 productive and epsilon germ-line transcripts, also expressed chimeric germ-line RNA (Iepsilon-Cgamma2) and epsilon-productive transcripts (VDJ-Cepsilon). This line had no further sequential Sgamma2-Sepsilon rearrangements, providing evidence that the productive VDJ-Cepsilon mRNA was derived from a transcriptionally active unrearranged epsilon gene locus by trans-splicing. Taken together, these results provide possible evidence that trans-splicing of germ-line Ig RNA transcripts occurs in human B cells.

Antibody Diversity↗
PubMed1996

Vasoactive intestinal peptide induces S(alpha)/S(mu) switch circular DNA in human B cells.

Vasoactive intestinal peptide (VIP), a major neurotransmitter of peripheral nerves, has been suggested to function in host defense by regulating local human immune function. Indirect evidence has been marshaled that VIP can function as a switch factor for IgA in human Ig isotype recombination. In this study we directly tested the ability of VIP to function as a factor driving human B cells into IgA producing cells by assessing its ability to induce switch circular DNA representing direct mu to alpha switching. In addition we determined the generation of alpha germ-line transcripts and measured the level of IgA protein produced. Stimulation with VIP and CD40 mAb induced IgA production by human IgD+ B cells while VIP or CD40 alone failed to do so. Stimulation of purified IgD+ B cells with VIP plus CD40 mAb induced generation of switch circular DNA representing in vitro driven isotype switching from mu to alpha. CD40 mAb alone induced alpha germ-line transcripts but not IgA switch circles. Thus VIP, a neurogenic factor, can induce alpha-specific switching in CD40-activated human B cells and may thereby play an important role in directing the humoral immune response at mucosal surfaces.

B-Lymphocytes↗
PubMed1996

Direct evidence that gamma 1 and gamma 3 switching in human B cells is interleukin-10 dependent.

Interleukin-10 (IL-10) has various effects on B cell immunoglobulin (Ig) production. Indirect evidence suggests that IL-10 functions as a switch factor for IgG production. In this study, the switch deleted Ig gene DNA was isolated and characterized, as direct evidence that IL-10 induced isotype switching in human B cells. In addition, 16 chimeric Ig fragments were isolated, representing deleted DNA generated by in vitro isotype switching from mu to gamma in human B cells, following stimulation with IL-10 and anti-CD40 monoclonal antibodies (CD40 mAb). These clones consisted solely of S gamma 1/S mu and S gamma 3/S mu chimeric switch circular DNAs, no S gamma 2/S mu or S gamma 4/S mu switch DNA was observed. In addition, IL-10 alone induced only gamma 1 and gamma 3 germ-line mRNA transcripts, as determined by restriction digestion of the reverse transcription-polymerase chain reaction products. Three modes of mu-gamma 3 isotype switching were detected: (1) direct switching; (2) internal deletion of S mu proceeding mu to gamma 3 switching; and (3) internal deletion of S gamma 3 proceeding mu to gamma 3 switching. These results directly demonstrate that gamma 1 and gamma 3 switching in human B cells is specifically induced by IL-10 in the presence of CD40 mAb.

Antibodies, Monoclonal↗
PubMed1995

IL-4 plus CD40 monoclonal antibody induces human B cells gamma subclass-specific isotype switch: switching to gamma 1, gamma 3, and gamma 4, but not gamma 2.

Stimulation with IL-4 plus CD40 mAb is known to induce production of IgE and IgG4. In this study, we determined the IgG subclass specificity of IL-4 plus CD40 mAb stimulation for human purified B cells. We determined true in vitro switching by the generation of switch circular DNA (S gamma/S mu) representing primary S mu/S gamma events and production of gamma subclass-specific germ-line transcripts by a combination of reverse transcription-PCR and restriction endonuclease digestion. We simultaneously measured changes in the levels of IgG subclass proteins produced. Forty-two clones of circular switch DNA were identified and sequenced. The IgG subclass of S gamma fragment in the S gamma/S mu chimeric PCR products was determined by analyzing key S gamma nucleotides. The switch-deleted clones were found to consist of S gamma 1/S mu, S gamma 3/S mu, and S gamma 4/S mu chimeric switch sequences, showing that such switching had occurred. No S gamma 2/S mu chimeric switch sequences were found. While a consensus sequence was not identified at the S gamma/S mu breakpoints, four contiguous guanines (GGGG) were noticeably present in the S gamma region near the breakpoint. The induction of gamma 1, gamma 3, and gamma 4 switch circles in human purified B cells was accompanied by enhanced production of IgG1, IgG3, and IgG4 but not IgG2. Similarly, stimulation with IL-4 alone induced gamma 1, gamma 3, and gamma 4 but not gamma 2 germ-line transcripts. These results demonstrate that IL-4 plus CD40 mAb induces Ig isotype switch from mu to gamma 1, gamma 3, and gamma 4 but not to gamma 2.

Antibodies, Monoclonal↗
PubMed1995

Heat shock enhances the susceptibility of tumor cells to lysis by lymphokine-activated killer cells.

OBJECTIVE: To determine whether heat-treated thyroid cancer cells augment the susceptibility of target cells to lysis by autologous lymphokine-activated killer cells. DESIGN: Peripheral blood lymphocytes from patients with thyroid cancer were incubated with recombinant interleukin 2 (100 U/mL) for 7 days, and thyroid cancer cells obtained from surgical specimens were heated at 44 degrees C for 20 minutes and incubated at 37 degrees C for 18 hours before performing the radioactive chromium Cr 51 release assay. RESULTS: The susceptibility of heat-treated thyroid cancer cells to lysis by autologous and allogeneic lymphokine-activated killer cells was significantly greater than that of untreated tumor cells. The mechanism of enhanced susceptibility was unclear. However, the effect depended on de novo protein synthesis, because inhibition of RNA synthesis by dactinomycin completely abolished the heat-enhanced susceptibility of tumor cells. CONCLUSION: Immunotherapy combined with hyperthermia may be useful in management of thyroid cancer.

Adenocarcinoma, Papillary↗
PubMed1994

Swainsonine augments the cytotoxicity of human lymphokine-activated killer cells against autologous thyroid cancer cells.

OBJECTIVE: Swainsonine (SW), an inhibitor of mammalian Golgi alpha-mannosidase II, blocks the processing of high mannose to complex type oligosaccharides. In this study, the effect of SW on the cytotoxicity of lymphokine-activated killer (LAK) cells against autologous thyroid cancer was investigated. DESIGN: Peripheral blood lymphocytes from patients with thyroid cancer were incubated with recombinant interleukin 2 (100 U/mL) and 0.5 mg/L of SW for 7 days, and thyroid cancer cells obtained from surgical specimens were pretreated with SW (0.5 mg/L) for 18 hours. The cytotoxicity of SW-treated LAK cells against tumor cells tested in a standard 4-hour radioactive chromium Cr 51 release assay. RESULTS: The cytotoxicity of SW-treated LAK cells against autologous thyroid cancer cells was found to be significantly greater than that of standard LAK cells incubated with interleukin 2 alone. The N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester esterase activity of LAK cells, this activity being a cytotoxic factor that is necessary for the lethal hit stage, was also increased by SW treatment. Further, thyroid cancer cells incubated with SW, as compared with nontreated tumor cells, showed much higher susceptibility to LAK killing. CONCLUSIONS: Our results suggest that SW might have potential immunomodulatory properties in the treatment of thyroid cancer.

Adenocarcinoma, Papillary↗
PubMed1993

Free peroneal and its composite flap: a distant donor for head and neck reconstruction.

Free peroneal or its composite flap from the leg has been transferred in four patients for oro-mandibular and hypopharyngeal defects following surgery for malignancy. These flaps were successfully transplanted in all patients: two cases of free peroneal flap and two of free fibular graft with skin with no resulting problems with the leg. The peroneal osteocutaneous flap offers the following advantages: The axial vessels are preferable for microvascular surgery. Two flaps can be used with two cutaneous branches. A flap measuring up to 16 x 4.5 cm can be utilized with primary closure at the donor site. A long bone can be obtained together with skin. Surgery on the neck and harvesting of the flap can be done at the same time. The donor site is not conspicuous.

Aged↗
PubMed1992

The presence of concanavalin-A(Con-A)-like molecules on natural-killer (NK)-sensitive target cells: their possible role in swainsonine-augmented human NK cytotoxicity.

In the present study we examined the expression of concanavalin-A(Con-A)-like molecules on natural-killer (NK)-sensitive target cells and investigated their possible role in the human NK-cell phenomenon. The incubation of either peripheral-blood lymphocytes (PBL) or large granular lymphocytes (LGL) with swainsonine (SW), an inhibitor of mannosidase II, resulted in the augmentation of cytotoxicity against K562 leukemia cells. The enhanced cytotoxicity was associated with increased binding of fluorescein isothiocyanate-conjugated Con-A to SW-treated effector cells, and immunofluorescence staining of the target K562 cells using goat anti-Con-A antibody (Ab) showed a significant positive shift in the flow cytometric pattern. Electrophoretic separation and immunoblotting analysis revealed that 4 components with a molecular weight of approximately 95, 80, 60 and 50 kDa were recognized by anti-Con-A Ab from the detergent-extract of K562 cells. The addition of Con-A during the antibody incubation step of the Western blotting abolished their expression, thus excluding non-specific binding of the antibody. The addition of Con-A also strongly inhibited the cytotoxicity of SW-treated effector cells (PBL or LGL) against K562 cells, and this inhibition was abolished by 40 mM alpha-methyl-mannopyranoside (alpha-MM), which binds to Con-A. Furthermore, Con-A increased the binding frequency of SW-treated LGL to K562, in spite of the inhibited cytotoxicity, and this effect could be neutralized by the further addition of alpha-MM. Our results suggest that Con A-like molecules might play an important role in cell-cell interactions between SW-treated effector cells and NK target cells.

Adenosine Triphosphate↗
PubMed1992

Chemosensitivity of head and neck cancer with the rapid thymidine incorporation assay and its clinical application.

The chemosensitivity of various head and neck cancers was investigated with the 5-day rapid thymidine incorporation assay in soft agar culture. The evaluability rate was 56%. Head and neck cancers were sensitive in vitro, in decreasing order, to peplomycin, cisplatin, bleomycin, 5-fluorouracil, mitomycin C, and doxorubicin. Primary tumors and neck metastases exhibited the same sensitivity, with 21% of all specimens tested responding. In vitro chemosensitivities were similar among patients younger than 69 years of age and those older than 70. The predictive accuracy for sensitivity tested prospectively in five cases was 80% and that for resistance in four was 75%.

Aged↗
PubMed1991

[Reconstruction with peroneal free flap after ablation of head and neck cancer].

One-stage reconstruction of head and neck defects following radical surgery was performed for two patients with the peroneal flaps which had the peroneal artery, vein and their branches as a pedicle. These flaps were viable without any post-operative complications. The advantages of these flaps are described as follows. (1) The subcutaneous fat is thin, and thus the flap is flexible and not bulky. (2) The diameters of the peroneal artery and vein are relatively large and the pedicle is long. (3) A pretty large size of the flap can be utilized. (4) A relatively long bone can be obtained together with skin at the same time, and the angle of the fibula can be easily changed. (5) Bleeding is little when the flap is taken out. (6) The resection of the tumor and the harvest of the flap can be done at the same time, due to different surgical areas. (7) The skin graft to the donor defect is not necessary, and the defect can be closed at one-stage. (8) The donor site does not stand out. Thus, this method is cosmetically excellent. This procedure has many advantages. Reconstruction with the peroneal flap offers a safe, reliable, and versatile method.

Aged↗
PubMed1990

Responses of killer cells in head and neck cancer patients.

The immunological functions of 60 patients with head and neck cancers were evaluated using in vitro natural killer cell (NK) activity, lymphokine activated killer cells (LAK) and OK-432 activated killer cells, as well as by in vivo purified protein derivative (PPD) and Su-PS skin tests. There were significant differences of the above three activities between stage I cancer patients and stage III and/or IV. The PPD skin test corresponded significantly to LAK activity, while Su-PS corresponded significantly to OK-432 activated killer cell activity. Responses to interleukin-2 and OK-432 of stage IV patients with head and neck cancers were different from those of stage IV with gastrointestinal cancer. These in vitro assays were very useful for the evaluation of immunological function in head and neck cancer patients, especially before any biological response modifying treatment.

Adult↗
PubMed1990

Studies on the Caldwell-Luc operation with or without counteropening at the inferior meatus.

The Caldwell-Luc operation was performed on 38 patients with and without the counteropening at the inferior meatus in order to investigate whether the opening is necessary or not. The blood loss with the opening was 108 g more on average than that on the side without it. The operation time was 11 min longer in the group with a counteropening. The differences in these two items were statistically significant. The difference in cheek swelling with both methods was not statistically significant. Postoperative conditions followed up to over 2 years showed no significant differences on both sides. The establishment of the counterdrainage at the inferior meatus is not necessary considering operation time, blood loss, possibility of nasolacrimal duct injury and early postoperative conditions.

Ethmoid Sinusitis↗