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Biomedical subjects

Y Okayama

Publications and source records attributed to Y Okayama.

At least 19 recordsLinked to original sources
PubMed2001

A comparison of mediators released or generated by IFN-gamma-treated human mast cells following aggregation of Fc gamma RI or Fc epsilon RI.

The high affinity receptor for IgG (Fc gamma RI, CD64) is expressed on human mast cells, where it is up-regulated by IFN-gamma and, thus, may allow mast cells to be recruited through IgG-dependent mechanisms in IFN-gamma-rich tissue inflammation. However, the mediators produced by human mast cells after aggregation of Fc gamma RI are incompletely described, and it is unknown whether these mediators are distinct from those produced after activation of human mast cells via Fc epsilon RI. Thus, we investigated the release of histamine and arachidonic acid metabolites and examined the chemokine and cytokine mRNA profiles of IFN-gamma-treated cultured human mast cells after Fc gamma RI or Fc epsilon RI aggregation. Aggregation of Fc gamma RI resulted in histamine release and PGD(2) and LTC(4) generation. These responses were qualitatively indistinguishable from responses stimulated via Fc epsilon RI. Aggregation of Fc epsilon RI or Fc gamma RI led to an induction or accumulation of 22 cytokine and chemokine mRNAs. Among them, seven cytokines (TNF-alpha, IL-1beta, IL-5, IL-6, IL-13, IL-1R antagonist, and GM-CSF) were significantly up-regulated via aggregation of Fc gamma RI compared with Fc epsilon RI. TNF-alpha mRNA data were confirmed by quantitative RT-PCR and ELISA. Furthermore, we confirmed histamine and TNF-alpha data using IFN-gamma-treated purified human lung mast cells. Thus, aggregation of Fc gamma RI on mast cells led to up-regulation and/or release of three important classes of mediators: biogenic amines, lipid mediators, and cytokines. Some cytokines, such as TNF-alpha, were released and generated to a greater degree after Fc gamma RI aggregation, suggesting that selected biologic responses of mast cells may be preferentially generated through Fc gamma RI in an IFN-gamma-rich environment.

Cells, Cultured↗
PubMed2001

IgG-dependent activation of human mast cells following up-regulation of FcgammaRI by IFN-gamma.

It has been reported that FcgammaRI is up-regulated on human mast cells (huMC) by IFN-gamma and aggregation of this receptor using mouse F(ab')(2) specific for receptor-bound, mouse anti-CD64 F(ab')(2) results in activation. To determine whether huMC can similarly be stimulated by aggregation of FcgammaRI-bound human IgG, IFN-gamma-treated, CD34(+)-derived, cultured huMC were sensitized with human immunoglobulins and activation was evaluated following addition of antibodies specific for each IgG isotype. Degranulation was also examined following simultaneous IgG- and IgE-dependent aggregation of FcgammaRI and Fc(epsilon)RI. Activation of IFN-gamma-treated huMC sensitized with 100 ng/ml IgG(1) resulted in 40% beta-hexosaminidase (beta-hex) release; minimal degranulation was observed using IgG(2), IgG(3) or IgG(4). IgG(1)-dependent activation led to PGD(2) and LTC(4) generation as well as elevated cytokine production, most notably TNF-alpha. Preincubation of cells with F(ab')(2) from CD64-specific clones 10.1 and 32.2 reduced IgG(1)-mediated beta-hex release by 46% and 74%, respectively. While IgG-dependent cell stimulation induced half-maximal degranulation by 11 min, IgE-dependent activation resulted in half maximal responses within 1 min. Simultaneous activation of huMC via FcgammaRI and Fc(epsilon)RI led to additive degranulation using suboptimal concentrations of IgG(1) and IgE. Activation of huMC thus may occur via monomeric IgG and FcgammaRI thereby providing a novel paradigm for huMC recruitment into inflammation.

Cell Degranulation↗
PubMed2001

A solid cystic tumor of the pancreas with ossification and possible malignancy, coexisting nonfusion of the pancreatic ducts.

We report the case of a 34-year-old woman with a solid cystic tumor (SCT) of the pancreas accompanied by ossification and possible malignancy, coexisting nonfusion of the pancreatic ducts. There was a 24 x 29 x 33-mm mass with a prominent calcified lesion in the tail of the pancreas detected by abdominal ultrasonography, computed tomography, and magnetic resonance imaging. There were no distal metastases detected. Endoscopic retrograde pancreatography revealed nonfusion of the pancreatic ducts. The resected tumor consisted of solid and cystic components. The tumor was not encapsulated and included a severely ossified lesion inside. On microscopy, the tumor cells were small, eosinophilic, and proliferated in a solid or pseudo-papillary pattern. The tumor cells infiltrated into the surrounding normal pancreas parenchyma and invaded part of the mesentery. The immunostaining was positive for alpha-1-antitrypsin, neuron-specific enolase, vimentin, and chromogranin A. In the literature, only a few cases of SCT of the pancreas described ossification. As far as we know, only three cases of SCT of the pancreas, which demonstrated nonfusion of the pancreatic ducts, have been reported. Thus, SCT of the pancreas with ossification, possible malignancy, and coexisting nonfusion of the pancreatic ducts is extremely rare.

Adult↗
PubMed2001

Secretion of interleukin-1 receptor antagonist from human mast cells after immunoglobulin E-mediated activation and after segmental antigen challenge.

Mast cells produce substances with antiinflammatory properties in addition to their capacity to release proinflammatory mediators. To further probe the antiinflammatory aspect of mast-cell function we investigated the ability of human mast cells (huMCs) to produce interleukin (IL)-1 receptor antagonist (IL-1ra) in response to high-affinity Fc receptor for immunoglobulin E (Fcalpha RI) aggregation, and examined IL-1ra in bronchoalveolar lavage fluid (BALF) to determine whether it might be of mast-cell origin. Using a ribonuclease protection assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA), IL-1ra message and protein were found to be constitutively expressed in cultured huMCs. Upon stimulation through Fcalpha RI, IL-1ra message was upregulated in huMCs and IL-1ra protein secreted from cultured huMCs and isolated human lung mast cells. By immunoblot analysis, huMCs were found to produce the 17-kD form of IL-1ra and the presence of IL-1ra in human lung mast cells was confirmed by immunohistochemistry. In BALF obtained from allergic asthmatic subjects, IL-1ra production increased after specific antigen challenge, with the 17-kD isoform of IL-1ra predominating. These findings demonstrate that huMCs produce and release IL-1ra after Fcalpha RI aggregation, which may contribute to a local inhibition of IL-1-dependent effects on inflammation in the lung.

Allergens↗
PubMed2000

Expression of a functional high-affinity IgG receptor, Fc gamma RI, on human mast cells: Up-regulation by IFN-gamma.

Biologically relevant activation of human mast cells through Fc receptors is believed to occur primarily through the high-affinity IgE receptor Fc epsilon RI. However, the demonstration in animal models that allergic reactions do not necessarily require Ag-specific IgE, nor the presence of a functional IgE receptor, and the clinical occurrence of some allergic reactions in situations where Ag-specific IgE appears to be lacking, led us to examine the hypothesis that human mast cells might express the high-affinity IgG receptor Fc gamma RI and in turn be activated through aggregation of this receptor. We thus first determined by RT-PCR that resting human mast cells exhibit minimal message for Fc gamma RI. We next found that IFN-gamma up-regulated the expression of Fc gamma RI. This was confirmed by flow cytometry, where Fc gamma RI expression on human mast cells was increased from approximately 2 to 44% by IFN-gamma exposure. Fc epsilon RI, Fc gamma RII, and Fc gamma RIII expression was not affected. Scatchard plots were consisted with these data where the average binding sites for monomeric IgG1 (Ka = 4-5 x 108 M-1) increased from approximately 2,400 to 12,100-17,300 per cell. Aggregation of Fc gamma RI on human mast cells, and only after IFN-gamma exposure, led to significant degranulation as evidenced by histamine release (24.5 +/- 4.4%): and up-regulation of mRNA expression for specific cytokines including TNF-alpha, GM-CSF, IL-3 and IL-13. These findings thus suggest another mechanism by which human mast cells may be recruited into the inflammatory processes associated with some immunologic and infectious diseases.

Antibody Affinity↗
PubMed1999

Interleukin-3 production by mast cells from human lung.

The cytokine interleukin (IL)-3 is important in the proliferation of eosinophils and basophils in the airway. We investigated IL-3 production by human lung mast cells as a possible mechanism of the airway inflammation constituting the late asthmatic response. Mast cells were purified using affinity magnetic selection with the monoclonal antibody YB5.B8 and then stimulated with anti-human IgE antibody. IL-3 release was detectable by enzyme-linked immunosorbent assay 8 h after anti-IgE stimulation. IL-3 release 24 h after anti-IgE stimulation was significantly greater than its controls. By reverse transcription-polymerase chain reaction, IL-3 mRNA was detected weakly 2 h after anti-IgE stimulation, peaking at 4 h and waning at 8 h. Immunocytochemistry to localize IL-3 demonstrated mast cell staining. These results suggest that mast cells release IL-3 in response to high-affinity IgE receptor.

Antibodies, Anti-Idiotypic↗
PubMed1999

Interleukin-10 is localized to and released by human lung mast cells.

BACKGROUND: Mast cells control the local inflammation by producing many kinds of cytokines. Interleukin (IL)-10 is one of the important cytokine that upregulate or downregulate inflammation. OBJECTIVE: The aim of this study is to ascertain whether IL-10 is produced from human lung mast cells by cross-linkage of high-affinity Fcepsilon receptors (FcepsilonRI). METHODS: Mast cells were purified using affinity magnetic selection with mAb YB5.B8 (> 93% pure). Mast cells were precultured with human myeloma IgE (3 microg/mL) for 16 h and then washed, and stimulated with anti-IgE in the presence or absence of recombinant human stem cell factor (rhSCF). We have studied the production of IL-10 by using reverse transcription-PCR, enzyme-linked immunosorbent assay and immunocytochemistry. RESULTS: We found that human lung mast cells were immunocytochemically stained with anti-IL-10 mAb after IgE-dependent stimulation. The activation of mast cells via FcepsilonRI enhanced the intensity of the IL-10 mRNA signal. Anti-IgE (1 microg/mL) induced a median IL-10 release of 301.7 (7.8-1532.4) pg/106 mast cells/24 h. In contrast, mast cells released only a small amount of IL-10 in the absence of anti-IgE. This difference was statistically significant (P = 0.02, n = 11). CONCLUSION: Our findings indicate that human lung mast cells are capable of producing IL-10 in response to IgE-dependent stimulation.

Antibodies, Anti-Idiotypic↗
PubMed1998

Human lung mast cells are enriched in the capacity to produce granulocyte-macrophage colony-stimulating factor in response to IgE-dependent stimulation.

By using reverse transcription-PCR, in situ hybridization, enzyme-linked immunosorbent assay and immunocytochemistry, we have studied the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) in human lung mast cells induced by cross-linkage of high-affinity Fc epsilon receptors (Fc epsilonRI). We have also confirmed the bioactivity of GM-CSF released from lung mast cells by investigating the effect of the supernatant from lung mast cells activated with anti-IgE on the release of eosinophil cationic protein (ECP) from eosinophils. Mast cells were purified using affinity magnetic selection with monoclonal antibody (mAb) YB5.B8 (93-99% pure). Purified mast cells were precultured with IgE for 16 h before challenge with 1 microg/ml anti-IgE with or without stem cell factor (SCF). Eosinophils were purified by immunomagnetic negative selection (> 98% pure). The activation of mast cells via Fc epsilonRI enhanced the intensity of the GM-CSF signal within 2 h and the cells produced GM-CSF protein 4 h after the activation. In the absence of recombinant human (rh) SCF, anti-IgE induced a median GM-CSF response of 202 (< 15 to approximately 681) pg/10(6) mast cells/24 h, whereas in the presence of rhSCF the median IgE-dependent GM-CSF release was 356 (152 to approximately 1216) pg/10(6) mast cells/24 h. This difference was statistically significant (p = 0.0029, n = 12). In contrast, mast cells produced only a small amount of GM-CSF in the absence of anti-IgE. The mast cell supernatant induced ECP release from eosinophils and the release was significantly inhibited by blocking mAb against GM-CSF. These findings indicate that human mast cells are an important cellular source of GM-CSF and as such may contribute to chronic eosinophil-mediated inflammation.

Blood Proteins↗
PubMed1998

Production of IL-13 by human lung mast cells in response to Fcepsilon receptor cross-linkage.

BACKGROUND: Cross-linkage of the high affinity Fcepsilon receptors (FcepsilonRI) on the surface of the mast cell by the allergen-IgE complex is a central event in the induction of allergic inflammatory reactions. However, the precise roles of human mast cells in the perpetuation of allergic inflammation is not well known. IL-13 plays an important role in the regulation of allergic inflammation, especially being involved in the induction of IgE synthesis. OBJECTIVE: We investigated whether human lung mast cells have the capacity to produce IL-13 by cross-linking of the FcepsilonRI. METHODS: Lung mast cells were purified by affinity magnetic selection with monoclonal antibody YB5.B8 against c-kit to achieve a final mast cell purity of more than 93%. Purified mast cells were precultured with human myeloma IgE (3 microg/mL) for 16 h before challenge with stem cell factor (SCF) (50 ng/mL) and anti-IgE (1 microg/mL). By RT-PCR, ELISA and immunocytochemistry, we evaluated the capacity of human lung mast cells to express and produce IL-13. RESULTS: IgE-dependent activation of human lung mast cells caused an increase in IL-13 mRNA expression which persisted for up to 12 h. Immunoreactive IL-13 was detectable 24 h after activation of sensitized lung mast cells with SCF and anti-IgE in 6 of 13 non-asthmatic donors and a million of mast cells secreted 106.7 +/- 42.65 (mean +/- SE) pg of IL-13 into the culture supernatants. SCF alone induced 61.63 +/- 31.12 pg of IL-13 from 106 mast cells. This difference was statistically significant (P = 0.028, n = 13). Furthermore, we confirmed by immunocytochemistry that immunological activation induced an increase of intracellular IL-13. CONCLUSION: These findings demonstrate the capacity of human lung mast cells to transcribe IL-13 after IgE-dependent activation and to synthesize and release IL-13.

Cells, Cultured↗
PubMed1998

Human skin mast cells produce TNF-alpha by substance P.

Using in situ hybridization and the reverse transcriptase polymerase chain reaction (RT-PCR) we show that messenger RNA for IL-4, IL-5 and tumor necrosis factor-alpha (TNF-alpha) is induced by cross-linkage of high-affinity Fc(epsilon) receptors (Fc(epsilon)RI) on human skin mast cells, but that only TNF-alpha mRNA is selectively induced by substance P. Skin mast cells were purified using the Percoll density technique. T cells were removed by serial negative selection using a CD2 monoclonal antibody (mAb) to achieve a final mast cell purity >95%. Purified mast cells were precultured with recombinant human stem cell factor (rhSCF; 10 ng/ml) and myeloma IgE (3 microg/ml) for 16 h before challenge with sheep polyclonal antihuman IgE antibody (anti-IgE; 1 or 10 microg/ml) in the presence of rhSCF (50 ng/ml). Using in situ hybridization, we demonstrated that IgE-dependent stimulation induces the expression of IL-4, IL-5 and TNF-alpha mRNA in skin mast cells. We have investigated the expression of IL-4, IL-5 and TNF-alpha mRNA by substance P, with the result that substance P, 0.003-30 microM, selectively induced TNF-alpha mRNA. However, substance P did not induce IL-4 mRNA and did not enhance IL-5 mRNA. Furthermore, we confirmed the release of TNF-alpha by substance P from skin mast cells using an ELISA technique. These findings demonstrate the capacity of human skin mast cells to transcribe IL-4, IL-5 and TNF-alpha by immunological activation and to transcribe and release TNF-alpha by substance P.

Base Sequence↗
PubMed1998

Retroperitoneal malignant fibrous histiocytoma causing variegated colonic lesions.

A 68-year-old man visited our hospital because of heartburn. A firm mass was palpated in the left upper abdominal quadrant. Ultrasonography and computed tomography revealed a large left sided retroperitoneal tumor. A barium enema examination showed shallow irregularly depressed or elevated lesions. Colonoscopy revealed an irregularly shaped ulcer and multiple submucosal masses suggesting invasion by an extrinsic malignant tumor. Although colonoscopic biopsy was negative, a resected tumor was histologically diagnosed as a malignant fibrous histiocytoma (MFH). When such varigated lesions are detected in the colon, MFH should be considered, and an attempt to sample the submucosal layer may be necessary.

Aged↗
PubMed1997

Activation of eosinophils with cytokines produced by lung mast cells.

Here we show that the supernatant from activated lung mast cells induced the release of eosinophil cationic protein (ECP) from eosinophils. Lung mast cells were purified using affinity magnetic selection with monoclonal antibody (mAb) YB5.B8 to achieve a final mast cell purity of 93-99%. Eosinophils were purified by immunomagnetic negative selection (>98.0% pure). The supernatant was obtained from lung mast cells activated for 24 h with 1 microg/ml anti-IgE and 50 ng/ml stem cell factor (SCF). Human eosinophils were incubated with various concentrations of the supernatants for 4 h and ECP released was measured by RIA. Using 4 different donors' supernatant from mast cells, each donor's supernatant caused a dose-dependent release of ECP from eosinophils. The dilutant of 1:2 (v/v) of the supernatant induced 657.5 +/- 55.6 ng/10(6) eosinophils of ECP which is statistically significant (p = 0.008, n = 4) compared with the culture medium alone. Anti-interleukin (IL-5 neutralizing mAb, 10 microg/ml, and anti-tumor necrosis factor-alpha (TNF alpha) neutralizing mAb, 10 microg/ml, significantly inhibited the supernatant-induced ECP release in 79.3 +/- 9.4 and 68.2 +/- 14.1% (mean +/- SEM, n = 6, p < 0.005), respectively. Anti-granulocyte/macrophage colony-stimulating factor (GM-CSF) neutralizing mAb, 50 microg/ml, caused 68.0 +/- 6.1% of inhibition (p = 0.002). The isotype negative control had no measurable inhibitory or stimulatory effect for the stimuli. We confirmed that mast cells produce IL-5, GM-CSF and TNF alpha in response to IgE-dependent stimulation by using RT-PCR, in situ hybridization, ELISA and immunocytochemistry. A million of lung mast cells generated 41.4 pg (7.0-273.6) (median with range) of TNF alpha, 252.6 pg (158.7-3,652) of GM-CSF and 735 pg (< 10-2,750) of IL-5 24 h after activation with SCF and anti-IgE. These findings indicate that the human mast cells may contribute to the chronicity of tissue inflammation.

Blood Proteins↗
PubMed1996

Single application extracorporeal shock wave lithotripsy is the first choice for patients with pancreatic duct stones.

OBJECTIVES: We performed extracorporeal shock wave lithotripsy (ESWL) as the treatment of first choice on 32 chronic pancreatitis patients with main pancreatic duct (MPD) stones prospectively to establish more convenient and safer treatment. METHODS: All patients were treated in a prone position, and shock waves were discharged from the ventral side. ESWL was performed once or twice a week, and no other treatments before ESWL had been applied. RESULTS: Disintegration of all MPD stones to 3 mm or less in diameter could be achieved in all treated patients. Complete clearance of the stones was obtained in 24 patients (75%) without the necessity of endoscopic extraction of fragments. Reduction of MPD diameters after ESWL was statistically significant (p < 0.01). Epigastric and/or back pain complaints before ESWL were completely alleviated in 79% (periods of follow-up: 16-63 months, mean 44), and the pancreatic exocrine function also improved in 61%. No severe complications occurred in any of the patients. CONCLUSIONS: ESWL, which is comparatively easy to perform, is a safe and efficient approach that changes endoscopy's status as an indispensable pretreatment. Therefore, ESWL can be recommended as the first choice treatment for patients with chronic pancreatitis accompanied by MPD stones that should be tried before consideration of either surgical or endoscopic procedures.

Adult↗
PubMed1995

IgE-dependent expression of mRNA for IL-4 and IL-5 in human lung mast cells.

By using the reverse transcriptase (RT)-PCR and in situ hybridization we have studied the expression of mRNA for IL-5 and IL-4 in human lung mast cells induced by cross-linkage of high affinity Fc epsilon Rs. Lung mast cells were purified using affinity magnetic selection with mAb YB5.B8 against c-kit to achieve a final mast cell purity > 93%. Purified mast cells were precultured with stem cell factor (SCF) (10 ng/ml) and myeloma IgE (3 micrograms/ml) for 16 h before challenge with anti-IgE (1 or 10 micrograms/ml). IgE-dependent activation of lung mast cells caused expression of IL-5 mRNA, which was evident by 2 h and persisted for up to 48-72 h in all of 12 experiments, whereas IL-4 mRNA expression was of a shorter duration and was demonstrable in 6 of 13 experiments. We confirmed that mast cells, and not T cells, were the source of these cytokine messages by using reverse transcriptase-PCR in cell preparations containing known numbers of mast cells and T cells, in situ hybridization in enriched mast cell preparations, and double in situ hybridization-immunocytochemical staining. IL-5 mRNA expression did not require the pretreatment of cells with SCF, whereas expression of IL-4 mRNA seemed to require both anti-IgE and SCF. The strength of IL-5 mRNA signal was related to anti-IgE concentration. Immunoreactive IL-5 was detectable 8 h after anti-IgE challenge, and 10(6) mast cells generated a mean of 731 +/- 400 pg of IL-5 into the supernatant during 48-h culture, but no IL-4 product was detectable. These findings demonstrate the capacity of human lung mast cells to transcribe IL-4 and IL-5 after IgE-dependent activation and to synthesize and release immunoreactive IL-5.

Base Sequence↗