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Biomedical subjects

T Kawabe

Publications and source records attributed to T Kawabe.

At least 19 recordsLinked to original sources

ADF (adult T cell leukemia-derived factor)/human thioredoxin and viral infection: possible new therapeutic approach.

ADF (adult T-cell leukemia-derived factor), originally defined as an inducer of interleukin 2 receptor/alpha (IL-2R/alpha), is a homologue of thioredoxin. ADF is constitutively produced by human lymphoid cell lines transformed by human T-lymphotropic virus type I (HTLV-I) or Epstein-Barr virus (EBV). ADF augments the proliferation of HTLV-I and EBV transformed cells as an autocrine growth factor. These data are indicative of the possible involvement of ADF in virus-related transformation of cells and their autocrine growth. On the other hand, thioredoxin contains a redox active disulfide and has a reducing activity in the presence of thioredoxin reductase and NADPH. To clarify the role of ADF/thioredoxin system in the viral transformation, we tested the effect of 13-cis-retinoic acid (RA), which is a competitive inhibitor of thioredoxin reductase, on the growth of ADF high producing cells. The expression of IL-2R/alpha on HTLV-I (+) cells was suppressed by RA. RA dose-dependently reduced the cell number and viability of ADF high producing lymphoid cells. Moreover, it had a suppressive effect on the proliferation of ADF high producing cells. It is suggested that RA has an inhibitory effect on the activation and the growth of cells producing ADF and that inhibition of the ADF/thioredoxin system may be a new therapeutic approach for retrovirus-related disorders.

Amino Acid Sequence

Cushing's syndrome induced by hypersecretion of cortisol from only one of bilateral adrenocortical tumors.

A case of Cushing's syndrome induced by the unilateral (right side) dominance of cortisol secretion in the face of bilateral adrenal tumors is reported. The adrenal tumor resected on the right side was a so-called black adenoma and histologically without any findings of nodular hyperplasia. After resection of the adrenal adenoma, no findings of cortisol hypersecretion from the remaining adrenal tumor on the left side were observed until the present, suggesting that the tumor of the left adrenal gland is a nonfunctioning adenoma. These data imply that the adrenal adenomas have primarily developed from the adrenal gland itself, rather than from micronodular hyperplasia by corticotropin stimulation, and that one of these tumors produces excess hormones initially by corticotropin stimulation, but the other remains in cell proliferation.

Adenoma

Mercury concentration correlates with the nitrogen stable isotope ratio in the animal food of Papuans.

The relationships among element concentrations (Na, Mg, Al, P, K, Ca, Cr, Fe, Mn, Cu, Zn, Sr, total Hg, organic Hg, inorganic Hg, Pb) and stable carbon and nitrogen isotope ratios (13C/12C and 15N/14N) in animals consumed by the people called Gidra, who inhabit the lowland of Papua New Guinea, were examined. Animals analyzed included mammal, bird, fish, shellfish, reptile, crustacean, and insect. Highly significantly positive correlations were observed between total Hg concentrations and 15N/14N (r = 0.796), between organic Hg concentrations and 15N/14N (r = 0.781), and between inorganic Hg concentrations and 15N/14N (r = 0.739). This was interpreted to indicate that Hg was an element which accumulates in animals along the food chain. Based on the regression function of Hg on delta 15N, the bioconcentration factor for total, organic, and inorganic Hg was estimated to be 5.

Diet

Induction and function of Fc epsilon RII on YT cells; possible role of ADF/thioredoxin in Fc epsilon RII expression.

The regulation of low-affinity Fc receptor for IgE (Fc epsilon RII) and the characteristics of both membrane and soluble forms of Fc epsilon RII were studied using YT cell line. We found that YT cells, a human NK like cell line, expressed Fc epsilon RII after IL-1 stimulation. Cross-linking of Fc epsilon RII on IL-1-stimulated YT cells as well as the transfectant of Fc epsilon RII-cDNA (YTSER) resulted in the up-regulation of IL-2R alpha (p55/Tac). A 59 kDa protein phosphorylated at tyrosine residues was co-immunoprecipitated with Fc epsilon RII from YTSER lysate using H107 anti-Fc epsilon RII mAb. YTSER not only expressed Fc epsilon RII on their surface but also secreted soluble form of Fc epsilon RII (sFc epsilon RII/sCD23; IgE binding factor). Affinity purification revealed that sFc epsilon RII released from YTSER is heterogeneous and consisted of several proteins differing in molecular weight. Both EBV+ B cells and HTLV-1+ T cells are high producers of ATL derived factor (ADF)/thioredoxin (TRX) and express Fc epsilon RII and IL-2R alpha respectively. To clarify the mechanism of Fc epsilon RII and IL-2R alpha induction by ADF/TRX, we examined the effect of ADF/TRX on the bindability of nuclear factor kappa B (NF-kappa B), which is known to regulate IL-2R alpha gene expression. In the gel shift assay, ADF/TRX was shown to enhance the bindability of NF-kappa B to its responsive element.

Base Sequence

Exercise performance in essential hypertension with special reference to blood pressure response and left ventricular hypertrophy.

Exercise performance in essential hypertension (EH) and its relations to blood pressure (BP) response and left ventricular hypertrophy (LVH) were studied. Twenty-three patients with mild to moderate EH and 12 controls underwent symptom-limited (except BP elevation more than 250 mm Hg) ergometer exercise. Exercise performance was evaluated by the oxygen uptake (VO2/kg) at anaerobic threshold (AT) and at peak exercise (Peak). Left ventricular geometry and function, and left ventricular mass index (LVMI) were measured using echocardiography. The endpoints of 12 patients (group A) and controls were fatigue. The endpoints of 11 patients (group B) were BP elevation. Though both group A and group B had concentric hypertrophy, group B showed severe LVH compared to group A and controls. The VO2/kg at AT or at Peak was not different among the three groups. Neither BP response or LVMI correlated with exercise performance in EH. We conclude that exercise performance is not disturbed in EH; that BP response to exercise is not related to exercise performance in EH; and that concentric LVH may be a compensatory mechanism to maintain exercise capacity against exaggerated BP elevation in EH.

Adult

Human thioredoxin/adult T cell leukemia-derived factor activates the enhancer binding protein of human immunodeficiency virus type 1 by thiol redox control mechanism.

Transcription from the human immunodeficiency virus type 1 (HIV-1) provirus is activated by a cellular factor, NF kappa B, recognizing the tandemly repeated 10-base-pair sequences, termed the kappa B sequence, present in the enhancer region within the viral long terminal repeat (LTR). Using electrophoretic mobility shift assay (EMSA), which demonstrates specific DNA-protein interaction in vitro, we could demonstrate that reducto-oxidative modulation of NF kappa B dramatically changes its DNA binding activity and that a cellular physiological reducing catalyst, thioredoxin (TRX) also known as adult T cell leukemia derived factor (ADF), fully restored the DNA-binding activity of the oxidized NF kappa B. We also observed that purified TRX/ADF protein could augment gene expression from HIV LTR as demonstrated by transient chloramphenicol acetyltransferase (CAT) assay. These observations confirmed the previous notion that ADF might be an inducing factor of cellular interleukin-2 receptor alpha subunit (IL-2R alpha) through the kappa B sequence that is a common central cis-regulatory element in both IL-2R alpha and HIV gene expression. These observations indicate that reducto-oxidative regulation (or redox regulation) of a cysteine residue(s) on the NF kappa B molecule might play an important role in its specific DNA interaction and that it might provide a clue to the understanding of a pathway of cellular signal transduction to NF kappa B that is independent from the known pathways involving protein phosphorylation.

Amino Acid Sequence

[Comparison of treadmill exercise, handgrip, and cold-pressor tests: with particular reference to the effects on hemodynamics, respiratory gas exchange, and sympathetic nervous activity].

The treadmill test (TM), handgrip test (HG) and cold-pressor test (CP) are now frequently used clinically for multiple purposes. However, gas exchange analysis has not been a common procedure during HG. In particular, during CP, it has not been previously reported. Relationships between these 3 tests and blood pressure, heart rate (HR), respiratory gas exchange and the sympathetic nervous activity of normal subjects have not been reported, either. This study was undertaken to clarify these points. Symptom-limited TM was performed in 11 normal male subjects with a mean age of 45 +/- 8 yrs according to the Bruce protocol, with the HG using the weight-sustaining method (equal weight of 50% maximal voluntary contraction) for 3 min, and CP for 2 min. Systolic and diastolic blood pressures (Ps, Pd) were recorded; HR was measured every 30 sec, and gas exchange variables, such as oxygen uptake (VO2) and carbon dioxide production, were documented every 10 sec using an aereomonitor AE-280 (Minato Medical Science Co). In 10 of 11 subjects, concentrations of plasma noradrenaline (PNA) and plasma adrenaline (PAD) were measured at rest and at the times of peak values of the 3 tests. The peak values of Ps and HR were much higher during TM than during HG and CP (p < 0.01), while the peak values of Pd during HG and CP were higher than during TM (p < 0.01). The VO2 increased significantly for all of the 3 tests (TM: +781%, HG: +65%, CP: +20%), with the increment being the greatest during TM. Both PNA and PAD increased significantly for the 3 tests, with the increments of PNA and PAD being the greatest during TM. The percent change in PAD was more prominent during HG and CP than during TM. This tendency was not as clear for PNA as for PAD. There was no correlation of delta Ps and delta Pd between the 3 tests, but values of delta HR correlated partially. No significant correlations of peak VO2 were observed between the 3 tests. The peak PNA correlated between HG and CP (r = 0.77, p < 0.01), and the peak PAD correlated between TM and CP (r = 0.67, p < 0.05). In summary, numerous differences in hemodynamic and respiratory responses and in sympathetic nervous activation were observed in the 3 tests. When the 3 tests are undertaken, careful attention should be paid for their characteristics, discrepancies and limitations.

Adult

Immunosuppressive activity induced by nitric oxide in culture supernatant of activated rat alveolar macrophages.

Alveolar macrophages (AM) from normal rats had immunosuppressive activity to mitogen-induced proliferative responses of splenic lymphocytes. We studied the mechanism and the implication of the nitric oxide synthetase pathway in AM-mediated suppression of concanavalin A (Con A)-induced lymphocyte proliferation. The culture supernatant from AM cultures alone did not have immunosuppressive activity to Con A-induced proliferative responses of non-adherent spleen cells (n-ad SC), but the culture supernatant from co-culture of AM and autologous n-ad SC had this activity. Con A-pulsed AM also liberated the immunosuppressive factor. When AM and autologous n-ad SC were cultured separately under the condition that medium could freely communicate, the culture supernatant did not suppress the Con A-induced proliferative response of n-ad SC. This indicated that the immunosuppressive factor was liberated when AM was activated by cell-to-cell contact with n-ad SC. Further, we examined the immunosuppressive activity of the culture supernatant of co-culture of AM and autologous n-ad SC to Con A-induced responses of allogeneic n-ad SC and xenogeneic murine n-ad SC, and allogeneic mixed leucocyte reaction, and found that this culture supernatant could suppress all these proliferative responses. Nitrate (NO2-) synthesis was markedly augmented in the culture supernatants of Con A-pulsed AM and co-culture of AM and n-ad SC. NG-monomethyl-L-arginine (MMA), a specific competitive inhibitor of the nitric oxide synthetase pathway (NOSP), extinguished both NO2- synthesis by AM and AM-mediated immunosuppressive activity. These data suggest that NOSP was important in AM-mediated suppression of Con A-induced lymphocyte proliferation.

Animals

Induction of Fc epsilon RII/CD23 on PHA-activated human peripheral blood T lymphocytes and association of fyn tyrosine kinase with Fc epsilon RII/CD23.

Despite the evidence for the expression of Fc epsilon RII/CD23, a glycoprotein that is a low-affinity Fc receptor for IgE, obtained on T cell lines and some pathological T cells, that of Fc epsilon RII/CD23 on normal human T cells is still unclear. We studied the emergence of T cells bearing Fc epsilon RII/CD23 in short-term culture of normal human peripheral blood mononuclear cells stimulated with 15 microliters/ml phytohemagglutinin (PHA). Using two-dimension flow cytometry, more than 10% of Fc epsilon RII/CD23(+) cells were shown to co-express CD3 antigen. Both CD4(+) and CD8(+) T cells expressed Fc epsilon RII/CD23. The expression of mRNA for Fc epsilon RII/CD23 on PHA and IL-4 stimulated PBMC was demonstrated by northern blotting and in-situ hybridization. The mechanism of signal transduction through Fc epsilon RII/CD23 was dissected by transfection of cDNA coding for Fc epsilon RII to the human natural killer-like cell line YT, activation of which was easily detected by the induction of interleukin-2 receptor/p55 (Tac). Cross-linking of Fc epsilon RII/CD23 with H107 anti-Fc epsilon RII monoclonal antibody enhanced IL-2R/p55 expression on YT cells transfected with Fc epsilon RII cDNA (YTSER). A possible involvement of protein-tyrosine kinase in the Fc epsilon RII-mediated signal transduction was studied using YTSER. Fc epsilon RII was physically associated with an src-family tyrosine kinase p59fyn and not with p56lck, which was also found in YT cells. Recently it was reported that p59fyn was associated with T-cell antigen receptor. Our results collectively suggest the multiple function of p59fyn which may be implicated in the Fc epsilon RII-mediated activation signal in YT cells.

Blotting, Northern

Fyn tyrosine kinase associated with Fc epsilon RII/CD23: possible multiple roles in lymphocyte activation.

Expression of low-affinity Fc receptor for IgE (Fc epsilon RII), which is identical to the lymphocyte differentiation antigen CD23, is associated with activation of lymphoid cells. The mechanism of signal transduction through Fc epsilon RII/CD23 was dissected by transfection of cDNA coding for Fc epsilon RII to the YT human natural killer-like cell line, activation of which was easily detected by the induction of interleukin 2 receptor/p55(Tac). Cross-linking of Fc epsilon RII/CD23 with H107 anti-Fc epsilon RII monoclonal antibody markedly enhanced interleukin 2 receptor/p55 expression on the YT cells transfected with Fc epsilon RII cDNA (YTSER cells). Similar induction of interleukin 2 receptor/p55 by the cross-linking of Fc epsilon RII was observed on an Epstein-Barr virus-transformed B-cell line, 3B6, and fresh leukemic cells isolated from a patient with B-cell chronic lymphoblastic leukemia. Thus Fc epsilon RII/CD23 provides activation signals not only in YTSER cells but also in activated B cells. A possible involvement of protein-tyrosine kinase in the Fc epsilon RII-mediated signal transduction was studied. Fc epsilon RII was physically associated with a src family tyrosine kinase p59fyn and not with p56lck, which was also found in YT cells. Recently it was reported that p59fyn was associated with T-cell antigen receptor. Our results collectively suggest the multiple functions of p59fyn that may be implicated in Fc epsilon RII-mediated activation signal in YT cells.

Antigens, CD

Induction of Fc epsilon RII/CD23 on phytohemagglutinin-activated human peripheral blood T lymphocytes. I. Enhancement by IL-2 and IL-4.

Despite evidence for the expression of low affinity Fc receptor for IgE (Fc epsilon RII)/CD23 in T cell lines and pathologic T cells, Fc epsilon RII/CD23 in normal human T cells is still unclear. We studied the expression of Fc epsilon RII/CD23 on T cells in short-term culture of normal human PBMC stimulated with 15 micrograms/ml PHA. PHA stimulation also resulted in the release of soluble Fc epsilon RII/CD23 (IgE binding factor). Using two-dimensional flow cytometry, more than 10% of the Fc epsilon RII/CD23+ cells were found to co-express CD3 Ag. Both CD4+ and CD8+ T cells expressed Fc epsilon RII/CD23. The induction of Fc epsilon RII/CD23 on PHA-activated T cells was enhanced by IL-2 as well as IL-4. Both IL-2 and IL-4 also augmented PHA-induced production of soluble Fc epsilon RII/CD23. The enhanced expression of Fc epsilon RII/CD23 on T cells by both lymphokines was suppressed by rabbit anti-IL-4 antiserum, suggesting the involvement of an IL-4-dependent process even in the IL-2-dependent Fc epsilon RII/CD23 expression on T cells. The expression of mRNA for Fc epsilon RII/CD23 on PHA and IL-4-stimulated PBMC was examined by Northern blot analysis. Fc epsilon RII/CD23 mRNA was detected in RNA prepared from the T cell fraction depleted of B cells and macrophages (Fc epsilon RII+CD3+ = 6.2%, Fc epsilon RII+CD3- = 0.8%). The expression of the mRNA for Fc epsilon RII/CD23 on CD3+ T cells was also confirmed by in situ hybridization with Fc epsilon RII/CD23 cDNA combined with CD3 rosette formation at the single cell level.

Antibodies, Monoclonal

A case of malignant lymphoma in the liver treated by percutaneous ethanol injection therapy under peritoneoscopic observation.

A 41-year-old woman with non-Hodgkin's lymphoma in the liver was treated with percutaneous ethanol injection therapy. Ethanol injection was performed twice under ultrasonographic guidance for a lesion inside the liver and once under peritoneoscopic observation for lesions on the surface of the liver. CT performed after treatment showed that sizes of the lesions decreased and that the lesions were not enhanced by contrast medium, indicating lack of blood supply and necrosis of the lesion. Ultrasonography performed after treatment did not show any lesions in the liver. There was no sign of recurrence or metastasis.

Adult

Serum levels of soluble IL-2 receptor, IL-4 and IgE-binding factors in childhood allergic diseases.

The serum levels of soluble IL-2 receptor (sIL-2R), IL-4 and IgE-binding factors were examined in children with allergic diseases, and compared with those in non-allergic controls of the same age and sex. The results showed age-related decreases in the serum levels of sIL-2R and IgE-binding factors, but not in that of IL-4 in both allergic and non-allergic individuals. Significant elevation of sIL-2R was observed in sera from children with atopic eczema or history of an anaphylactic reaction to food, as compared with that in non-allergic controls. The serum concentration of IL-4 was elevated in all allergic groups, including cases of atopic eczema, bronchial asthma and anaphylaxis to food, compared with non-allergic controls, and was correlated significantly with the serum level of IgE (r = 0.59). The IgE-binding factor levels in sera from patients aged 6-10 years with bronchial asthma, or patients aged 1-5 years with a history of food anaphylaxis were elevated as compared with those in non-allergic controls of same age. There was no significant correlation between the serum levels of IgE-binding factors and IgE. Since sIL-2R is released by activated T cells, the present study is in favour of T cell activation causing allergic skin disorders. The serum levels of IL-4 as well as IgE did not differ among allergic patients of different clinical categories. The role of IgE in atopic eczema and other allergic diseases is not clearly established; however, it seems likely that IL-4 is deeply involved in the increased production of IgE seen in allergic individuals. The possible involvement of IgE-binding factors in the age-related changes of clinical manifestations in childhood allergic diseases was also discussed.

Adolescent

[Syntheses and antifungal activities of 1-[4-phenyl-2-(phenylthio or acyloxy)-n-butyl]-1H-imidazole derivatives].

The title compounds (4b, d-f, h-j) were prepared from 1-[4-(p-substituted phenyl)-2-chloro-n-butyl]-1H-imidazoles and the corresponding thiophenols or mercaptopyridines. Acyloxy compounds (5a-e) were prepared from alcohol (2b) and the corresponding acyl chlorides. In the antifungal activity test, p-tolyl compounds (4e, f) showed as good activity as butoconazole (4c).

Drug Resistance, Microbial

[Remarkable effect of the combination therapy of etoposide, epiadriamycin, and CDDP (EAP) in the treatment of metachronous lung metastases of breast cancer--a case report].

A case of metachronous lung metastasis treated by the combination therapy of Etoposide, Epiadriamycin and CDDP (modified EAP) is reported. A 47-year-old female who had undergone standard radical mastectomy for left. breast cancer was shown to have multiple metastases to the right. lung two years and seven months after surgery. The metastatic lesions disappeared after six series of modified EAP (VP 16 450 mg + ADR 40 mg + CDDP 100 mg/body) x 6 in seven months. Major side effects such as leukopenia and thrombocytopenia were not observed during the course. No recurrence had been noted for 14 months since the disappearance of the metastatic lesions. It is thus emphasized that the effect of EAP may be expected for the treatment of breast cancer.

Adult

Role of PAF and cytokines in the modulation of Fc epsilon RII/CD23 expression on human eosinophils.

IL-4 and gamma IFN profoundly modulate the expression of the cell surface and soluble Fc epsilon RII/CD23 molecule, which is a low affinity Fc receptor for IgE having regulatory activity on immune system. IL-4 is a general inducer of Fc epsilon RII/CD23 on B lymphocyte, monocyte/macrophage, and eosinophil lineages, while gamma IFN counteracts the enhancing effect of IL-4 on normal B lymphocytes. However, the effect of gamma IFN is more complex than that of IL-4. gamma IFN up-regulates those on monoblast cell line U937 and eosinophil cell line EoL. This differential regulation of Fc epsilon RII/CD23 on B cells and the other cell types may play important roles in immune system, as macrophages and eosinophils are critical cells in the allergic reactions. In addition to cytokines, we found that platelet activation factor (PAF) up-regulates the expression of Fc epsilon RII/CD23, whereas transforming growth factor-beta (TGF-beta) and glucocorticosteroid (dexamethasone) down-regulate it on U937 and EOL cells. Variable and strong effect of these factors on the expression of CD23/Fc epsilon RII may indicate the involvement of this receptor system in the allergic as well as immune reactions and possibly the pathophysiology of the allergic and immunological disorders.

Antigens, CD

[The expression of IgE Fc receptors on peripheral blood monocytes in asthmatic patients].

We measured the expression of the IgE Fc receptor, Fc epsilon RII, on peripheral blood monocytes isolated from asthmatic patients and normal subjects by laser flow cytometry. After peripheral blood mononuclear cells were incubated with monoclonal antibodies, H107, which recognize Fc epsilon RII, FITC-labeled second antibodies were reacted with them. The cells were then incubated with PE-labeled Leu M3 monoclonal antibodies and the ratios of H107 positive monocytes were measured by two color analysis. The ratio of H107 positive monocytes in atopic asthmatic patients was significantly greater than the ratio in normal subjects. But the ratio was not higher in 9 out of the 14 atopic asthmatic patients. This indicated that atopic asthmatic patients are divided into two groups by the expression of Fc epsilon RII on monocytes. Total serum IgE level was not related to the ratio of H107 positive monocytes.

Adult