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N Seo

Publications and source records attributed to N Seo.

At least 55 records · Page 3Linked to original sources
PubMed1999

Lymphocyte stimulation test with drug-photomodified cells in patients with quinolone photosensitivity.

Quinolone antibacterial agents, known to elicit photosensitive dermatitis as an adverse effect, have both phototoxicity and photoallergenicity. The latter potency is mainly derived from their photohaptenic moiety; quinolones covalently bind to protein and cells upon exposure to ultraviolet A (UVA) light. Our previous study has shown the in vivo and in vitro antigenicity of quinolone-photomodified cells in mice. Here, we examined the presence of sensitized lymphocytes that react with quinolone-photomodified autologous cells in patients with photosensitivity to quinolones. A flow cytometric analysis using a monoclonal antibody specific to quinolone photoadducts demonstrated that peripheral blood mononuclear cells (PBMC) were successfully photomodified with quinolones upon exposure to UVA. PBMC from quinolone-photosensitive patients were cocultured with autologous PBMC photomodified with the causative drug. Modest but significant proliferative responses of responder lymphocytes were found in patients photosensitive to lomefloxacin, fleroxacin, and enoxacin, indicating photoallergic mechanism in these patients. On the other hand, sparfloxacin-photosensitive patients exhibited negative lymphocyte stimulation test, suggesting that its photosensitivity is mainly phototoxic. When UVA-preirradiated quinolones were used as stimulators, only fleroxacin exceptionally stimulated patients' PBMC, indicating its prohaptenic as well as photohaptenic properties. These findings suggest the presence of circulating sensitized T cells in patients with photosensitivity to certain quinolones.

Aged↗
PubMed1999

Modulation of T-lymphocyte proliferation by exogenous natural ceramides and sphingosylphosphorylcholine.

Sphingolipids such as ceramide and sphingosine are abundantly present in the stratum corneum of epidermis. In atopic stratum corneum, sphingosylphosphorylcholine (SPC) is present in association with a reduction in the amount of ceramides. We have previously shown that the cellular kinetics of T cells are affected by exogenous addition of sphingosine and synthetic ceramides, raising the possibility that sphingolipids diffusing from the stratum corneum modulate skin-infiltrating T cells. By using two natural ceramides and murine T cells, this study further clarified the conditions under which exogenous ceramides enhance the proliferation of T cells. KLH-specific T cell clones 28-4 and 24-2 proliferated in response to natural ceramides when cultured for 44-48 h in the presence of concanavalin A at 1 microg per ml. Elongation of culture periods adversely inhibited the T cell proliferation, suggesting the existence of an optimal exposure time. Augmentation of DNA synthesis by natural ceramides was more pronounced in tumor necrosis factor alpha (TNFalpha)-sensitive 28-4 cells than in less sensitive 24-2 cells, and TNFalpha-induced proliferation of 28-4 cells was suppressed by the concomitant addition of natural ceramides. Similar to ceramides, SPC augmented the proliferation of resting spleen cells. Our study suggests that ceramide modulation of T cell proliferation depends on the TNFalpha sensitivity and activation level of T cells and that SPC also has a mitogenic potential for T cells.

Animals↗
PubMed1999

Treatment of T lymphocytes with 8-methoxypsoralen plus ultraviolet A induces transient but biologically active Th1-skewing cytokine production.

8-Methoxypsoralen plus ultraviolet A light is suggested to shift T lymphocytes from Th2 to Th1 cells. To clarify this issue, we examined the effects of 8-methoxypsoralen/ultraviolet A on the expression/production of cytokines in peripheral blood mononuclear cells from normal subjects and a Sézary syndrome patient. 8-Methoxypsoralen/ultraviolet A augmented the expression of mRNAs for interferon-gamma and interleukin-2 and reduced those for interleukin-4 and interleukin-10. It seems that this enhancement of Th1 cytokines is caused by increment of cytokine production by Th1 cells but not by conversion of Th2 cells to produce Th1 cytokines. The number of interferon-gamma-secreting lymphocytes was markedly increased in 8-methoxypsoralen/ultraviolet A-treated peripheral blood mononuclear cells 20 h after treatment, whereas that of Th2 cytokine-producing cells was decreased. Accordingly, the amount of interferon-gamma was elevated in culture supernatants from 8-methoxypsoralen-phototreated peripheral blood mononuclear cells, whereas interleukin-4 was significantly reduced. This enhanced production of interferon-gamma, however, was found only until 3 d after 8-methoxypsoralen phototreatment and was declined by 5 d after treatment. Finally, 8-methoxypsoralen/ultraviolet A treatment of T cells regulated their ability to induce keratinocyte CD54 expression. Our results show that 8-methoxypsoralen/ultraviolet A has a transient but biologically active Th1-skewing action in human T cells, suggesting that 8-methoxypsoralen/ultraviolet A exerts a beneficial therapeutic effect on Th2-mediated or Th2-malignant diseases.

Cytokines↗
PubMed1999

Downregulation of innate and acquired antitumor immunity by bystander gammadelta and alphabeta T lymphocytes with Th2 or Tr1 cytokine profiles.

It has been thought that natural killer (NK) cells appearing early in tumor lesions play a pivotal role in the innate immunity against tumor cells. Although NK cells serve as the first tumoricidal effector cells, they subsequently promote a shift in effectors from themselves to tumor-specific cytotoxic T lymphocytes (CTLs) that mediate the acquired immunity. The mechanism of this shift has not been fully elucidated, however, NK cell-derived T helper (Th) 1 cytokines such as interferon (IFN)-gamma seem to play a key role. Another NK-lineage, termed natural killer T (NK T) cells, may also participate in the innate period when they acquire the ability to secrete Th1 cytokines. Interleukin-4 (IL-4) and IL-10, belonging to Th2, and transforming growth factor-beta (TGF-beta), belonging to T regulatory (Tr) 1 cytokines, are known to suppress the development of NK, NK T cells, as well as CTLs and to block Th0 cell differentiation to Th1 cells, suggesting that tumor cells can evade the innate and acquired immunity by virtue of cells producing these inhibitory cytokines. In early tumor lesions of murine B16 melanoma, gammadelta T and alphabeta intermediate (int) T cells that co-infiltrate with NK and NK T cells can produce Th2 cytokines and inhibit the innate immunity. In MM2 mammary tumor-bearing mice, gammadelta T cells appearing both lesionally and systemically secrete Tr1-type cytokines and depress the acquired immunity. These Th2- or Tr1-type gammadelta T and alphabeta(int) T cells downregulate the tumoricidal cells by means of both their secreted cytokines and express major histocompatibility complex (MHC) class I molecules.

Animals↗
PubMed1999

[Problems with employment of a staff anesthesiologist in a local hospital].

Yukiguni Yamato General Hospital (199 beds) is one of main local hospitals of Minamiuonuma area in Niigata prefecture. From June 1997, an anesthesiologist has been employed as a staff of this hospital instead of parttimers. We examined whether employment of an anesthetic staff was useful for a local hospital or not, in terms of clinical and cost advantages. There were benefits in explaining the nature of anesthesia, possible risks, operating room and pre-postoperative procedures to the patients. And there were advantages in reducing anesthetic management fee, in shortening the staying time in operating room. We conclude that there are many benefits in obtaining an anesthesiologist for a local hospital staff, but there are some drawbacks in having to work alone.

Anesthesiology↗
PubMed1998

Down-regulation of tumoricidal NK and NK T cell activities by MHC Kb molecules expressed on Th2-type gammadelta T and alphabeta T cells coinfiltrating in early B16 melanoma lesions.

We examined whether gammadelta T and alphabeta T cells accumulating in early B16 melanoma lesions regulate NK and NK T cells that attack tumor cells. Freshly isolated and cultured tumor-infiltrating lymphocyte (TIL) populations of NK and NK T cells lysed B16 and produced IFN-gamma, whereas gammadelta T and a large part of alphabeta T cell populations had no substantial cytotoxicity against B16 and secreted Th2 cytokines. Furthermore, the freshly isolated NK1.1+ TIL population exhibited a higher anti-B16 effect than did splenocytes. Gammadelta T and alphabeta T cell populations dramatically inhibited the cytotoxicity of NK and NK T cells in an MHC Kb-dependent manner. Culture supernatant from gammadelta T and alphabeta T cell populations inhibited the proliferation of NK and NK T cell populations but did not affect their cytotoxicity, suggesting that the released Th2 cytokines are merely partly involved in the down-modulation of NK-lineage cells. NK1.1+ cells obtained from TIL of gammadelta T cell-depleted mice significantly lysed B16 cells compared with those from control mice. Finally, anti-Kb Fab mAb injected intralesionally at an early, but not at a late, stage of development of B16 melanoma inhibited tumor growth. These findings suggest that Th2-type gammadelta T and alphabeta T cells infiltrating in early B16 development inhibit the tumoricidal activity of NK-lineage cells using their class I molecules and partly their suppressive cytokines.

Animals↗
PubMed1998

Cross-reactivity in murine fluoroquinolone photoallergy: exclusive usage of TCR Vbeta13 by immune T cells that recognize fluoroquinolone-photomodified cells.

Fluoroquinolone antibacterial agents are well known to elicit photosensitivity as an adverse effect, and their cross-reactivity has been clinically documented. The photoallergenicity of fluoroquinolones is mainly derived from their photohaptenic moiety, and photomodification of skin epidermal cells with fluoroquinolones is thought to be an initial step for this photoallergy. Here we have explored, both in vivo and in vitro, T cell responses to fluoroquinolone-photomodified cells, focusing on their photoantigenic cross-reactivity. Cells were derivatized with fluoroquinolones under exposure to UV-A, and fluoroquinolone photoadducts were detected in photomodified cells by immunostaining, flow cytometry, and cell ELISA using fluoroquinolone-specific mAb. T cell-mediated hypersensitivity induced and elicited by s.c. injection of fluoroquinolone-photomodified epidermal cells was cross-reactive among six fluoroquinolones. In addition, lymph node cells from mice sensitized with fluoroquinolone-photomodified cells proliferated well in vitro not only to Langerhans cell-enriched epidermal cells photoderivatized with corresponding fluoroquinolone, but also to those photomodified with any of five other fluoroquinolones, supporting their cross-reactivity. In three fluoroquinolones tested, Th1 populations that expanded after in vitro photoantigenic stimulation of immune lymph node cells expressed the same Vbeta13 of TCR. The sensitivity could be transferred by the i.v. administration of this Vbeta13+ T cell line into naive recipients, in which a high percentage of Vbeta13+ cells infiltrated at the challenge site. These findings suggest that these fluoroquinolones carry the same photoantigenic epitope, which is recognized by Vbeta13+ T cells, leading to fluoroquinolone photosensitivity and cross-reactivity.

Adoptive Transfer↗
PubMed1998

Tumour-specific cytotoxic T lymphocyte activity in Th2-type Sézary syndrome: its enhancement by interferon-gamma (IFN-gamma) and IL-12 and fluctuations in association with disease activity.

Sézary syndrome (SzS) is the leukaemic variant of cutaneous T cell lymphoma (CTCL), whose malignant T cells are of the Th2 type in most cases. In this study we investigated the tumouricidal activity of cytotoxic T lymphocytes (CTL) present in peripheral blood of a patient with Th2-type SzS, focusing on the effect of IL-2, IFN-gamma and IL-12 on their cytotoxic activity, and the relationship between their lytic capacity and the patient's clinical course. At four different time points during a 2-month clinical period, CD4+CD7- Sézary cells and CD8+ cells were separated from the patient's circulating cells. CD8+ cells were cultured with chemically attenuated, purified Sézary cells in the presence of IL-2 to develop specific cytotoxicity. The CD8+ cells thus cultured exhibited lytic activity against autologous Sézary cells. Concomitant addition of IFN-gamma or IL-12 exerted a synergistic cytolytic effect with IL-2 on the tumour cells. Cytotoxicity inhibition studies using MoAbs revealed that the cytotoxicity operated in MHC class I-, CD8- and alphabeta T cell receptor-dependent manners. Furthermore, eight CD8+ T cell clones generated from cultured CD8+ cells exhibited a strong cytotoxicity against Sézary cells in an MHC class I-restricted fashion. During the clinical course, the activity of generated CTL and the number of CD8+ cells were inversely correlated with disease activity as assessed by the serum level of lactate dehydrogenase. These findings suggest that CTL down-regulate the growth of malignant T cells in this long-standing disease. Since Th2 cytokines such as IL-4 down-modulate CTL activity, CTL are assumed to be usually suppressed in SzS, whose malignant T cells are of Th2 type. It is likely that the administration of IFN-gamma normalizes this Th2-skewing state, activates CTL, and thus exerts the therapeutic effectiveness in the treatment of CTCL.

Antigens, Neoplasm↗
PubMed1998

[Anesthesia for abdominal surgery after percutaneous transluminal coronary angioplasty (PTCA)].

From December 1989 to October 1996, 1,318 PTCAs (percutaneous transluminal coronaly angioplasty) were performed for AMI (acute myocardial infarction) or postinfarction angina in our institute. Within 7 days to 71 days after successful PTCA, five patients who had been diagnosed as cholelithiasis or gastric cancer were operated under general anesthesia. Performed operations were cholecystectomy in the first patient, subtotal gastrectomy in the second, third and fourth patients, and total gastrectomy and cholecystectomy in the fifth patient. There was no serious cardiac complication during the operations and perioperative period. PTCA is considered to have decreased cardiac complications in patients with ischemic heart disease having undergone abdominal surgery.

Abdomen↗
PubMed1997

Spontaneous hair follicle cycling may influence the development of murine contact photosensitivity by modulating keratinocyte cytokine production.

The development of murine contact hypersensitivity is influenced by hair follicle cycling. Here, we have examined hair cycle-associated fluctuations of murine contact photosensitivity (CPS) to tetrachlorosalicylanilide (TCSA) and its immunologic mechanism(s). When the CPS outcome was monitored in correlation with their spontaneous, synchronized hair cycling, mice aged 8 and 14 weeks, with most of their hair follicles in telogen, exhibited strong CPS responses, whereas 4-, 11-, and 16-week-old mice with a predominance of anagen follicles in a large area of their integument exhibited lower responses. This suggests that the development of CPS is inhibited in mice with anagen hair follicles. Antigen-specific, T-cell receptor V beta 7+ suppressor T cells, which are recognized to down-regulate the CPS response to TCSA, were not generated in sensitized anagen mice. Culture supernatants of epidermal cells derived from mice with anagen hair follicles contained factor(s) that suppress in vivo the development of CPS. It was found that levels of mRNA for tumor necrosis factor alpha (TNF alpha) were markedly decreased in epidermal cells from early anagen to telogen mice, whereas message for IL-1 receptor antagonist (IL-1ra) was transcribed increasingly during this hair cycling. These findings suggest that altered keratinocyte production of these cytokines is involved in mediating the anagen-associated depression of CPS.

Age Factors↗
PubMed1997

Magnetic resonance imaging of the extradural space of the thoracic spine.

To clarify the anatomy of the extradural space of the thoracic spine, we have compared magnetic resonance (MR) images of the thoracic spine with those of the lumbar spine. In 20 healthy volunteers, T2-weighted axial MR images were obtained at the levels of the C7-T1, T7-8, T11-12 and L2-3 vertebrae. The posterior extradural space seen in the slice through the intervertebral disc varied in shape and size depending on the vertebral level, and the shape of the space converted from triangular to crescent-shaped on moving from the lumbar to the thoracic spine. In particular, the posterior extradural space was almost absent at the C7-T1 level, indicating that the posterior extradural fat was rudimentary or non-existent at the thoracocervical level. At this level, the dura mater seemed to be in direct contact with the ligamentum flavum. Segmentation of the posterior extradural space was commonly observed at the L2-3 and T11-12 levels; however, incomplete segmentation of the posterior extradural space was often present at the T7-8 level.

Adult↗
PubMed1997

Altered permeability and disordered cutaneous immunoregulatory function in mice with acute barrier disruption.

In vivo and in vitro T-cell-activating ability of murine epidermal cells (EC) was investigated in acutely barrier-disrupted skin by extraction of epidermal lipids with acetone or removal of corneocytes by tape stripping. Contact sensitivity (CS) to 2,4-dinitrofluorobenzene (DNFB) and picryl chloride (PCl) and contact photosensitivity (CPS) to tetrachlorosalicylanilide (TCSA) were significantly augmented when challenged or sensitized at sites treated with acetone 24 h before, compared with the intact skin. CS to DNFB was also enhanced by tape stripping, but not by water rubbing, suggesting that physical stress or a toxic effect of acetone was not responsible for the augmentation. Semi-quantification of TCSA-EC photoadducts showed markedly increased permeability of hapten in the epidermis 24 h after acetone treatment. Bioactive IL-1alpha was more pronounced in barrier-disrupted than in intact skin. Lymph node T cells from PCl-sensitized mice proliferated significantly more in a hapten-specific and co-stimulatory molecule-dependent manner in response to trinitrophenylated (TNP) EC from acetone-treated skin than to those from untreated skin. Immunofluorescence staining of epidermal sheets and flow cytometric analysis of dispersed EC showed that subpopulations of Langerhans cells (LC) in acetone-rubbed or tape-stripped skin expressed major histocompatibility complex class II CD54 and CD86 molecules at levels higher than the rest of LC and LC from water-treated or untreated epidermis. Therefore, not only increased permeability of hapten through the epidermis but also altered immune functions of EC potentiate T-cell activation in acute barrier disruption. Such augmentation of immune reactivity may be critical to elimination of environmental noxious agents that penetrate easily into the barrier-disrupted epidermis.

Acetone↗
PubMed1997

Transient rise in serum cytokines during coronary artery bypass graft surgery.

In order to examine the specificity of cytokine production during coronary artery bypass graft (CABG) surgery, we serially measured serum levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF), in twenty patients between 52 and 80 years of age, during surgery and 2 days afterwards. Serum MCP-1, as well as IL-8 and IL-6, increased significantly during the surgery (P < 0.05), while IL-1 beta and TNF did not. MCP-1, IL-8 and IL-6 concentrations were not different in the sera of three patients tested at three different sites, i.e., the hepatic vein, pulmonary artery and radial artery. They increased in parallel in each patient, although the actual timing of the increase relative to the surgical step varied among individuals. In complicated patients, MCP-1, IL-8 and IL-6 showed higher peaks and persisted longer than in patients without complications. The universal and simultaneous appearance of MCP-1, IL-8 and IL-6 could indicate that these three cytokines may be stimulated by a yet undiscovered stimulus (or stimuli) which occurs systemically despite the independent pathways of production.

Aged↗
PubMed1995

Suppression of cytotoxic T lymphocyte activity by gamma/delta T cells in tumor-bearing mice.

Spleen cells derived from tumor-bearing mice prove useful for the elucidation of the mechanism determining how tumor cells evade cytotoxic T lymphocytes (CTL) in tumor-bearing hosts. Our data indicate that inactive CTL or precursor CTL specific for tumor antigens are present among lymphocytes of tumor-bearing mice. However, their activity is inhibited by a soluble factor produced by other cells present in the same source. Inhibition of the cytolytic reaction was also detected in the culture supernatant of spleen cells obtained from normal mice, precultured in the presence of tumor cell culture supernatant and interleukin-2 (IL-2). Cell-depletion and cell-purification studies let us conclude that cells that produced the CTL-inhibitory factor (CTL-IF) were gamma/delta T cells. The gamma/delta T cells that were activated in vivo in tumor bearers were able to produce CTL-IF after isolation and in vitro culture. Maximum activation of gamma/delta T cells was achieved by antigenic stimulation and by suppression of cells that interfered with the activation of gamma/delta T cells. CTL-IF, which was assayed by use of CTL clones, did not show antigen specificity. Inhibition depended on a relatively heat- and acid-stable, but alkali-labile molecule with a molecular mass of less than 10 kDa. The latter characteristics imply that CTL-IF does not resemble any of the known lymphokines produced by gamma/delta T cells. These observations emphasize the crucial role of the gamma/delta T cells in the escape of tumor cells from the attack of tumor-specific CTL.

Animals↗
PubMed1995

Protection against metastasis by immunization with an allogeneic lymphocyte antigen.

Q5 antigens are expressed on the surface of various experimental murine tumor cells. They share partially common antigenicity with Qa-2 alloantigens expressed on normal lymphocytes. For that reason we tested the immunoprotection by anti-Qa-2 immunization of mice against a Q5+ tumor. Nerve fibrosarcoma (NSFA) tumor, which specifically develops metastasis in the lung, has been reported to be poorly immunogenic. However, expression of the Q5 antigen was evident on the surface of NFSA cells. After immunizing (C3H/He x B6.K1)F1 (Qa-2-) mice with B6 (Qa-2+) lymphocytes, the protection against the proliferation of the semi-syngeneic NFSA tumor was examined. First, immunization of normal mice induced resistance to NFSA cell transplants. Second, when the tumor cells were transplanted to the hind foot of a mouse and the resulting tumor was removed by amputating the leg, the mice were protected against the development of lung metastasis after immunization by intraperitoneal inoculation of B6 cells 3 days after tumor removal. Immunization with attenuated NFSA cells in this system failed to protect the mice from lung metastasis. On the other hand, inoculation of the mice with B6 cells without removal of the original tumor on the foot showed little effect on the progression of the tumor. Thus, cytotoxic T lymphocytes (CTL), which seemed to be present in an inactive form in the mice from which the tumor had not been removed, were induced in the mice after the removal of the major tumor followed by immunization with B6 lymphocytes. The induction of CTL by the immunization was suppressed in mice bearing large tumors. Cells stimulated by the tumor antigen seemed to be involved in the suppression. It was also shown that the Q5 antigen is the direct recognition target of the CTL since the activity of Q5-specific CTL clones in lysing tumor cells was inhibited by a monoclonal antibody specific for the Q5 antigen. In contrast to immunization with attenuated tumor cells, our novel allogeneic lymphocyte immunization procedure offers high CTL activation, by-passing the induction of T cell unresponsiveness.

Amputation, Surgical↗