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M Hirashima

Publications and source records attributed to M Hirashima.

At least 55 records · Page 3Linked to original sources

Selective regulation of chemotactic lymphokine production by monocytes and macrophage cell line cells.

Effects of lipopolysaccharides (LPS) on the production of chemotactic lymphokines for eosinophils and monocytes (ECF and MCF) from antigen- or mitogen-stimulated T cells were examined. Supernatants from monocytes stimulated with various LPS regulated concanavalin A (Con A)- and purified protein derivative (PPD)-induced ECF or MCF production. The regulation varied with LPS used for monocyte stimulation. The supernatant from monocytes stimulated with LPS from Escherichia coli, J-5 strain, selectively potentiated ECF production, whereas that from Salmonella minesota potentiated MCF production. In contrast, supernatant from monocytes stimulated with LPS from Salmonella typhimurium potentiated both ECF and MCF production, whereas that from Vibrio cholerae failed to potentiate production. The supernatants from monocytes stimulated with lipid A of S. typhimurium, S. minesota, and E. coli, however, failed to potentiate ECF and MCF production. The potentiating activity for each lymphokine was recovered from fractions ranging in molecular weight between 10 and 20 kD. Further purification with isoelectric electrophoresis revealed that the potentiating activity for the production of chemotactic lymphokine for eosinophils has a pI value of about 4-5, and that the activity for MCF production is detected in two fractions of pI about 5-6, and 7-8. Macrophage lineage cell line cells, such as THP-1 and U-937, also release similar factors after differential stimulation.

Alum Compounds↗

Heterogeneous eosinophils of allergic rhinitis in chemotactic response.

Chemotactic responses of eosinophils from patients with allergic rhinitis to 5 STO-2-derived eosinophil chemotactic factors (ECF), IL-3, IL-5 and GM-CSF were examined. The patients were divided into two groups: patients with perennial allergic rhinitis sensitive to Dermatophagoides farinae and those with seasonal allergic rhinitis sensitive to Japanese cedar pollen. There was no essential difference between chemotactic response of eosinophils from the former to STO-2-derived ECF and that from healthy individuals. However, eosinophils from patients with seasonal allergic rhinitis failed to respond to one of the STO-2-derived ECFs, ECF-P19. Before and after nasal antigen provocation, no change occurred in the chemotactic profiles. Furthermore, we found that eosinophils from both types of patients with allergic rhinitis responded not only to IL-3 and GM-CSF but also to IL-5 unlike those of healthy individuals.

Cell Line↗

Chemotactic heterogeneity of eosinophils in Kimura's disease.

We evaluated the chemotactic heterogeneity of eosinophils in Kimura's disease. Patients with Kimura's disease were divided into two groups according to their clinical findings: one group had no other symptoms (KD), and another was accompanied with atopic dermatitis (KD + AD). The chemotactic response of eosinophils from two groups to 5 eosinophil chemotactic factors (ECF) derived from STO-2, an established T cell line. Eosinophils from KD were attracted only by ECF-PI5 and PI6 but not by ECF-PI7, PI8 and PI9. On the other hand, eosinophils from KD + AD responded to all 5 ECF. Eosinophils were further fractionated into normodense and hypodense eosinophils, and assessed for their chemotactic response. We thus found that there was little essential difference in their chemotactic responses to STO-2-derived ECF except ECF-PI9, though random migration of hypodense eosinophils was enhanced. The hypothesis that hypodense eosinophils are in the activated form was not always true, especially in the chemotactic response to ECF.

Angiolymphoid Hyperplasia with Eosinophilia↗

Effects of eosinophilotropic cytokines on differentiation of an eosinophil cell line, YY-1.

Differentiation of an eosinophilic cell line, YY-1, was induced by treatment with 0.3 mM butyric acid (BA). The effects of eosinophilotropic cytokines, such as IL-3, IL-5, and GM-CSF on BA-induced differentiation, especially in the chemotactic response to ECF, was examined. Five STO-2-derived ECFs, IL-5, C5a, and fMLP were used as eosinophil chemoattractants. The effects of the cytokines on the chemotactic response of YY-1 greatly differed according to the ECF used. It was thus suggested that heterogeneity in the chemotactic response of eosinophils depends on the cytokines which act on eosinophils during differentiation.

Cell Differentiation↗

[Radiological findings of gastric scirrhous cancer].

Gastric scirrhous cancer was classified from the radiological findings into three phases (typical, latent and early phases) by cancerous involvement in the gastric wall. Radiological findings in the typical phase were divided into a giant-fold type and a no giant-fold type. We made a differential diagnosis for scirrhous cancer and other diseases. Radiological findings in the typical phase of scirrhous cancer were characteristic stiffness and rigidity of the gastric wall; in the latent phase, they were swelling and winding of mucosal folds in appropriate distended stomach; and in the early phase, interrupted folds around barium fleck. The effect of chemotherapy against a gastric scirrhous cancer is decided by distensibility of the gastric wall in radiological findings.

Adenocarcinoma, Scirrhous↗

[Assessment of QOL in cancer drug therapy using 22-item questionnaire].

In order to integrate quality of life as the end point in the cancer drug therapy, a questionnaire form has been developed over the past four years by a Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare, Japan. Fifty-one items generated by questionnaires were forwarded to oncologists, nurses, psychologists and 121 patients. Then questionnaires were scaled down to 36 items based upon factor analysis considering correlation to State-Trait Anxiety Inventory (STAI) and Self-rating Depression Scale (SDS). These 36 items were administered to 536 patients. Finally, a 22-item questionnaire was completed by rechecking correlations with PS, STAI, SDS and Cronbach's alpha. It includes such components as physical activities (6 items), psychological (5 items) and social variables (5 items), symptoms (5 items) and global well-being (1 item: face scale). In our treatment of G. I. cancer by chemotherapy, NC patients showed improvement (+1.56 score), especially in physical functions (+2.43 score), but with slight deterioration (-0.25 score).

Female↗

Regulation of eosinophil migration by adult T cell leukemia-derived factor.

Adult T cell leukemia-derived factor (ADF), originally defined as an IL-2 receptor alpha-chain (IL-2R alpha)/p55 (Tac) inducer, is a human thioredoxin homologue and has many cytokine-like activities. In this study, we examined the regulatory effect of ADF on eosinophil migration using human eosinophils and an eosinophilic subline of HL-60 human promyelocytic leukemia cells, YY-1. rADF induced migration of eosinophils from patients with hypereosinophilia, although rADF exhibited little activity on eosinophils from healthy donors. When human eosinophils were incubated with rADF (0.1-10 micrograms/ml) at 37 degrees C for 24 h, both chemotactic and chemokinetic activity of the complement anaphylatoxin peptide C5a on eosinophil migration was markedly enhanced in a dose-dependent manner. Similarly, this enhancing effect of rADF was observed in the migration assay using YY-1 cells. In contrast, rADF showed no modulation of migratory behavior of human eosinophils and YY-1 cells by IL-3, IL-5, nor granulocyte-macrophage colony-stimulating factor. Scatchard analysis of C5a receptors on YY-1 cells using 125I-C5a showed that rADF modulated neither the density nor the affinity of the cell membrane significantly. Furthermore, mutant ADF (mADF), which had no reducing activity, had no enhancing effect on C5a-induced eosinophil migration. These results indicate a possible involvement of ADF in the recruitment of eosinophils through redox regulation by a dithiol reductase activity.

Adult↗

Induction of an eosinophil chemotactic factor production from T lymphocytes by a B cell lymphoma line.

Production of an eosinophil chemotactic factor (ECF) from human mononuclear leukocytes (MNL) was induced by coculture with an irradiated B cell lymphoma line, BALL-1. BALL-1 induced ECF production from OKT4-positive T lymphocytes without evident IL-2 production. Treatment of MNL with anti-IL-2 antibody failed to suppress the BALL-1-induced ECF production, whereas the treatment strongly inhibited IL-2-induced ECF production. Control supernatants of BALL-1 cells alone did not induce ECF production. BALL-1 fixed with periodate-lysine-paraformaldehyde, but not acetone or ethanol, induced evident ECF production. The isoelectric point of BALL-1-induced ECF (m.w. 10-30 kD) was around pI 7, whereas that of the IL-2-induced ECF was around pI 5. A combination of monoclonal antibodies against IL-3, IL-5, and GM-CSF suppressed the activity of the IL-2-induced ECF but not that of the BALL-1-induced ECF. BALL-1-induced ECF suppressed a respiratory burst from an eosinophilic cell line (YY-1) induced by N-formyl-L-methionyl-L-leucyl-L-phenylalanine, whereas the IL-2-induced ECF did not, suggesting that the biological function of these two ECF is different, at least in the effect on respiratory burst of eosinophils. From the present results we propose that one reason for infiltration of eosinophils into the stroma of tumors is that some tumor cells can stimulate OKT4-positive T lymphocytes to produce an ECF, and that eosinophils attracted by this ECF exhibit biological functions which are different from those of eosinophils attracted by other ECF.

Antibodies, Monoclonal↗

Detection of precore/core-mutant hepatitis B virus genome in patients with acute or fulminant hepatitis without serological markers for recent HBV infection.

To confirm the possibility that some hepatitis B virus (HBV) variants do not induce HB s antigen (HBsAg), anti-HB core antibody (anti-HBc) and anti-HBc IgM in a transient infection, polymerase chain reaction (PCR) was performed in 20 patients with acute hepatitis and 7 patients with fulminant hepatitis. Patients were diagnosed with non-A, non-B hepatitis by serological markers at admission. PCR successfully amplified the precore/core gene in 5 (25%) of the patients with acute hepatitis and 2 (29%) of the patients with fulminant hepatitis. Subsequent sequencing revealed frequent mutations including precore-defects in the precore/core gene.

Acute Disease↗

[Type IV allergic reaction (delayed type)].

In guinea pig system, we have shown that a T cell-derived eosinophil chemotactic factor (ECF) plays a role especially in delayed-in-time tissue eosinophilia. In Kimura's disease characterized by blood and tissue eosinophilia, OKT4-positive T cells from the patients spontaneously produce an ECF (LDECF-HES; pI 6) without any additional stimulation. A monocyte-derived factor with mw of greater than 100,000 induce LDECF-HES production from T cells. On the other hand, OKT4-positive T cells from patients with parasite infection produce another ECF (LDECF-PD; pI 7-8) during mitogenic or antigenic stimulation. LDECF-PD production is selectively potentiated by ECF-potentiating factor derived from monocytes. Furthermore we have shown that the two ECF differ in their effects on eosinophil chemotaxis, eosinophil cationic protein release and Fc receptor expression. Recently we have established a T cell line, STO-2, constitutively producing 5 ECF with different pI (5, 6, 7, 8 and 9). These 5 ECF have different biological activities in eosinophil survival, Fc receptor expression and induction of specific eosinophilic granules. Comparison of chemotactic response of eosinophils from various patients with eosinophilia to respective ECF has revealed that eosinophils are heterogeneous in their chemotactic activity.

Animals↗

Characterization of an eosinophilic leukemia cell differentiation factor (ELDF) produced by a human T cell leukemia cell line, HIL-3.

An adult T cell leukemia cell line, HIL-3, constitutively secretes a factor which induces the phenotypical and functional eosinophilic differentiation of a human eosinophilic leukemia cell line, EoL-1. Biochemical characteristics of the factor, termed eosinophilic leukemia cell differentiation factor (ELDF), were examined. ELDF was precipitated by 35 to 65% saturated ammonium sulfate from the culture supernatants of HIL-3 cells (HIL-3 sup). ELDF was eluted in a peak corresponding to a molecular weight of 30 to 40 kd by gel filtration. Isoelectric focusing in the Rotofor showed that ELDF had isoelectric points of 5 to 6. ELDF was trypsin-sensitive and stable to heat treatment at 65 degrees C for 30 minutes but labile at 80 degrees C or pH lower than 3. Half of the activity adhered to lentil-lectin but not to Con-A, indicating that a part of ELDF is glycoprotein with an N-linked carbohydrate moiety, which did not seem to be essential for ELDF activity. The biochemical characteristics of ELDF and blocking experiments using cytokine-specific neutralizing antibodies suggest that ELDF is different from gamma-interferon (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-5 (IL-5) and interleukin-2 (IL-2), which may exist in HIL-3 sup, and that ELDF may be a previously unrecognized leukemia differentiation factor.

Cell Differentiation↗

Nucleotide sequence of the third cytokine LD78 gene and mapping of all three LD78 gene loci to human chromosome 17.

Cytokine LD78 is a member of a newly identified cytokine superfamily. We cloned the third human gene for the LD78, termed LD78 gamma and the sequence analysis showed that it is a 5'-truncated pseudogene. Exons 2 and 3 and the intron between them are highly homologous to those of the LD78 beta gene, hence, the gamma gene was probably derived from the beta gene. Southern blot analysis of human x mouse somatic hybrid cell DNAs and in situ hybridization experiments mapped all the three gene loci on human chromosome 17q21.1-q21.3. Analysis of DNAs from family members supports our previous finding that the beta and gamma genes on each of the paired chromosome 17 vary in copy number and that the LD78 alpha gene is presumably a single copy. In our analyses of cosmid clones, the LD78 beta gene and the second gene for AT744, which is also a member of the superfamily are closely linked in a head-to-head arrangement. The mechanism of generation of the three LD78 genes is discussed.

Base Sequence↗

Establishment of a human T-cell line constitutively producing several eosinophil chemotactic lymphokines and their functional heterogeneity on eosinophils.

We established a T-cell line, STO-2, by human T-cell lymphoma-leukemia virus-induced transformation of normal human T cells. Partial purification with isoelectric electrophoresis revealed that STO-2 liberated several eosinophil chemotactic factors (ECF) for eosinophils from healthy individuals with different isoelectric point of PI5, PI6, PI7, PI8, and PI9. Molecular weight of all the ECF was about 30,000 to 45,000. None of the ECF except ECF-PI5 was suppressed when they were incubated with monoclonal antibodies against IL-3, IL-5, and GM-CSF together, suggesting that ECF activity of ECF-PI5 is mainly comprised of IL-3, IL-5, and GM-CSF. ECF-PI5, PI6, and PI7 also exhibited enhancing activity on ex vivo eosinophil survival whereas ECF-PI8 and PI9 failed. Expression of Fc epsilon receptor II on eosinophils was potentiated by ECF-PI6 and ECF-PI7. In contrast, expression of Fc gamma receptor III was potentiated by ECF-PI7, ECF-PI8, and ECF-PI9. ECF-PI6 could also change an eosinophilic cell line, EOL-1, to eosinophilic granule-positive cells, whereas the rest of ECF failed. The above results suggested that eosinophils attracted by an ECF exhibit their biological functions, which differ from those of eosinophils attracted by other ECF. In further experiments, the chemotactic response of eosinophils from patients with eosinophilia was compared to that of eosinophils from healthy individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Line, Transformed↗

Functional heterogeneity of human eosinophil chemotactic lymphokines.

We have previously isolated two OKT4-positive T lymphocyte-derived eosinophil chemotactic factors (LDECF) with MW of about 45-60 kDa of which production is different in antigen or mitogen dependency (1-4). The production of a LDECF from patients with parasite disease (LDECF-PD) is dependent on antigen or mitogen stimulation, whereas another LDECF from patients with hypereosinophilic syndrome (HES) is independent. Further purification of these LDECF with isoelectric focusing reveals that an isoelectric point of LDECF-HES is about 6.0 and that of LDECF-PD is around 7.0 to 8.0. Little or no activity of partially purified LDECF-HES and LDECF-PD is suppressed by treatment with monoclonal antibodies against GM-CSM, IL-3, and IL-5, which activate eosinophils. LDECF-HES and LDECF-PD attract eosinophils from healthy individuals. In contrast, eosinophils from patients with HES are attracted by LDECF-HES but not LDECF-PD. LDECF-HES enhances the expression of Fc epsilon receptor II (Fc epsilon RII) and Fc gamma receptor III (Fc gamma RIII) but not that of CR1 on eosinophils, whereas LDECF-PD enhances their CR1 and Fc gamma RIII expression but not Fc epsilon RII expression. Moreover, treatment with LDECF-PD suppresses the release of eosinophilic cationic protein (ECP) from eosinophils, whereas that with LDECF-HES fails. Treatment of eosinophils with phorbol myristate acetate enhances ECP release from eosinophils but it fails to enhance the intracellular ECP level. However, the intracellular ECP level is elevated by stimulation with phorbol myristate acetate if eosinophils were previously treated with LDECF-HES but not with LDECF-PD. These results suggest that various kinds of LDECF are produced according to the nature of diseases, and that each LDECF has functional heterogeneity on eosinophils.

Antigens, Surface↗

Selective potentiation of lymphocyte-derived macrophage chemotactic factor release in complete Freund's adjuvant-treated guinea pigs.

Dinitrophenol (DNP)-ovalbumin(OA)-induced tissue macrophage reaction in sensitized guinea pigs is enhanced by treatment with complete Freund's adjuvant (CFA). The enhancement of the reaction may be due to the increased production of a T-lymphocyte-derived macrophage chemotactic factor (LDMCF) because treatment of animals with CFA potentiates antigen- and concanavalin A(ConA)-induced release of LDMCF activity from spleen cells of the CFA-treated animals in vitro. This potentiating effect by CFA seems to be ascribed to the release of an adherent-cell-derived soluble factor from the CFA-treated animals. The adherent cell-derived factor, LDMCF-potentiating factor (LDMCF-PF), preferentially potentiates the release of LDMCF activity but not of eosinophil chemotactic activity from antigen- or Con-A-stimulated T lymphocytes. Protein synthesis is required for release of LDMCF-PF. Molecular weight of LDMCF-PF activity is assumed to be about 10,000-20,000. LDMCF-PF activity is sensitive to trypsin, to neuraminidase, and also to alkalinity at pH 11, suggesting that LDMCF-PF is a glycoprotein. The present study provides one explanation for the enhanced macrophage reaction in delayed-type hypersensitivity reactions.

Animals↗

Production of an eosinophil chemotactic lymphokine by a monocyte-derived factor from patients with hypereosinophilia.

Peripheral OKT4-positive T lymphocytes from patients with hypereosinophilia spontaneously and selectively produced an eosinophil chemotactic factor (ECF) with chemokinetic activity. The molecular weight of the ECF was about 45,000 to 70,000. A possible mechanism of its spontaneous production by T lymphocytes was analyzed. Culture supernatants of blood monocytes from the patients showed little or no ECF activity, but they had a potency to induce the ECF production from T lymphocytes from normal donors when the cells were stimulated by the supernatants, which suggests that a monocyte-derived soluble factor (MDF) stimulated T lymphocytes to produce an ECF resembling this spontaneously produced ECF from the patients. MDF seemed to be a synthesized protein by the cells. Gel filtration indicated that molecular weight of MDF ranged between 70,000 and 100,000. MDF activity was stable at 56 degrees C for 30 min but more, supernatants of stimulated monocytes by lipopolysaccharide or silica particles failed to show ECF-producing activity, whereas they showed evident lymphocyte-activation activity. Neither recombinant IL-1 nor IL-2 had ECF and ECF-producing activity. From the present experiments, it was suggested that MDF was at least partly involved in the induction of ECF production by OKT4-positive T lymphocytes in patients with hypereosinophilia.

Adult↗

The regulation of tissue eosinophilia. V. Induction of lymphocyte-derived eosinophil chemotactic inhibitory factor production by a macrophage product from complete Freund's adjuvant-treated guinea pigs.

Splenic T lymphocytes of complete Freund's adjuvant (CFA)-treated guinea pigs spontaneously produce a lymphokine, eosinophil-directed chemotactic inhibitory factor (ECIF), which selectively inhibits the chemotactic response of the treated eosinophils to a certain chemotactic lymphokine for eosinophils. In the present paper, induction of spontaneous ECIF production was examined in CFA-treated guinea pigs. Although short-time (3-hr) cultured supernatants of CFA-treated spleen cells exhibited little or no ECIF activity, the supernatants could stimulate normal T lymphocytes to produce and release distinct ECIF activity. The factor with ECIF-releasing activity (ECIF-RF) was produced by splenic adherent cells of CFA-treated animals. ECIF-RF activity was absorbed only by T lymphocytes, suggesting that target cells of ECIF are T lymphocytes. ECIF-RF activity was eluted near cytochrome c (MW 12,500) on a Sephadex G-100 column. It was further found that ECIF-RF was sensitive to heating at 56 degrees C, to enzyme treatment with trypsin and neuraminidase, and to acid and alkaline condition. We thus concluded that ECIF-RF derived from adherent cells of CFA-treated animals may be involved in the suppression of cell-mediated tissue eosinophilia by stimulation of T lymphocytes to produce and release ECIF activity.

Animals↗