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Biomedical subjects

M Takigawa

Publications and source records attributed to M Takigawa.

At least 163 records · Page 9Linked to original sources
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

Influence of dietary zinc on convulsive seizures and hippocampal NADPH diaphorase-positive neurons in seizure susceptible EL mouse.

Adequate, high and deficient dietary levels of zinc (Zn) were compared in seizure-susceptible EL mice with respect to convulsions and to nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase-positive hippocampal neurons. Diaphorase positivity is associated with nitric oxide (NO) production. Convulsive seizures in the EL mice given the various diets did not differ over 1-4 weeks, but convulsions in EL mice given the Zn-deficient diet for 4 weeks were more effectively suppressed by injection of zonisamide (ZNS) (75 mg/kg intraperitoneally) than in mice receiving high- or adequate-Zn diet for the same period. Numbers of NADPH diaphorase-positive neurons in the CA1/CA2 region of the hippocampal formation were significantly higher in mice given the Zn-deficient diet for 4 weeks than in mice fed adequate Zn. Mice receiving the high-Zn diet for the same period had significantly fewer NADPH diaphorase-positive neurons in the subiculum than mice with adequate Zn. These results suggest that Zn deficiency inhibits convulsive seizures of EL mice, and that dietary Zn influences numbers of NO producing neurons in the hippocampal formation.

Animals↗
PubMed1998

Mental status of the elderly receiving home health services and the associated stress of home helpers.

One hundred and ninety elderly people receiving home health service were investigated. The intellectual levels, depressive state evaluated by the Cornell scale for depression in dementia (CSDD) scale, abnormal behaviors evaluated by the dementia behavior disturbance (DBD) scale, and activities of daily living (ADL) were examined. These assessments were performed by 72 skilled home helpers who also assessed the severity of their own level of stress using the Burnout scale. The intellectual level and mood-related signs, based on the CSDD scale, of the elderly living with families or with a spouse were diminished significantly as compared to the elderly living alone. The elderly living with families also performed worse on all ADL categories except for visual acuity as compared to the elderly living with a spouse or living alone. There was no significant correlation between the Burnout scale score and age or frequency of working as a home helper. These results suggest that elderly people living with families as compared to the elderly living with a spouse or living alone have greater mental health needs as well as more profound physical limitations.

Activities of Daily Living↗
PubMed1998

Increased expression of connective tissue growth factor in the infarct zone of experimentally induced myocardial infarction in rats.

Connective tissue growth factor (CTGF), a 36- to 38-kDa peptide, is selectively induced by transforming growth factor-beta and has been suggested to contribute to tissue repair. To test the hypothesis that CTGF is expressed in myocardial infarct tissue following acute myocardial infarction (AMI), we examined CTGF expression after AMI was experimentally induced in rats. Myocardial infarction was induced by left coronary artery ligation in male Sprague-Dawley rats. Northern blotting demonstrated that the CTGF mRNA expression on days 2, 7 and 14 was increased by 6-, 23- and 8-fold, respectively, compared to that in the pre-ligation hearts. In situ hybridization revealed CTGF mRNA signals on day 2 in myocytes in the infarct marginal zone and spindle-shaped mesenchymal cells (presumably myofibroblasts and fibroblasts) located between surviving myocytes in the infarct peripheral zone. On day 7, the signals were observed in the inner lesion of the infarct around infarct granulation tissue. Western blotting demonstrated that the CTGF protein expression on days 2, 7 and 14 was increased compared to the pre-ligation hearts. Immunopositive staining for CTGF was observed in the inner lesion of the infarct tissue on day 7. In conclusion, the findings demonstrated the increased expression of CTGF in the infarct tissue. Myocytes in the infarct marginal zone and spindle-shaped mesenchymal cells (presumably myofibroblasts and fibroblasts) were the cells responsible for CTGF production.

Animals↗
PubMed1998

Regulation of peripheral blood mononuclear cell responses to Dermatophagoides farinae by substance P in patients with atopic dermatitis.

Neuropeptides mediate stress-induced cutaneous inflammation such as atopic dermatitis. The effect of substance P on proliferation and cytokine mRNA expression of peripheral blood mononuclear cells in response to Dermatophagoides farinae (Der f) was studied in atopic dermatitis patients with positive RAST scores to Der f. Upon stimulation with Der f peripheral blood mononuclear cells from patients proliferated in a B7-dependent (CD80- and CD86-dependent) manner, while those from the patients with negative scores, nonatopic eczematous dermatitis patients or normal individuals, did not. Based on the reactivity of normal individuals, atopic dermatitis patients with a stimulation index greater than 1.8 were tentatively defined as high responders, who comprised two-thirds of the patients. Proliferation in high responders was associated with upregulation of IL-2 mRNA expression and induction of IL-5 mRNA expression. Substance p at 10(-10) to 10(-8) M promoted the Der f-induced proliferation when added at the start of culture and upregulated IL-10 MRNA expression while downregulating IL-5 mRNA expression. Our results suggest that substance P modifies immune responses of atopic T cells to Der f by promoting proliferation and altering cytokine profiles, and thus modulates the clinical manifestations of atopic dermatitis.

Adolescent↗
PubMed1998

Expression of osteopontin in Meckel's cartilage cells during phenotypic transdifferentiation in vitro, as detected by in situ hybridization and immunocytochemical analysis.

The localization of osteopontin (OP) was examined in Meckel's cartilage cells that bipotentially expressed cartilage and bone phenotypes during cellular transformation in vitro. Cultured cells were analyzed by in situ hybridization, immunostaining followed by light and electron microscopy, electron microscopy, and electron probe microanalysis. The combination of ultrastructural analysis and immunoperoxidase staining indicated that OP-synthesizing cells were cells that were autonomously undergoing a change from chondrocytes to bone-forming cells at the top of nodules. Double immunofluorescence staining of 2-week-old cultures revealed that OP was first synthesized by chondrocytic cells at the top of nodules. After further time in culture, the distribution of OP expanded from the central toward the peripheral regions of the nodules. Electron probe microanalysis revealed that the localization of OP was associated with matrices of calcified cartilage and osteoid nodules that contained calcium and phosphorus. Immunoperoxidase electron microscopy revealed that, in addition to the intracellular immunoreactivity in chondrocytes and small round cells that were undergoing transformation, matrix foci of calcospherites and matrix vesicles, in particular, included growing crystals that were immunopositive for OP. An intense signal due to mRNA for OP in 3-week-old cultures was detected in nodule-forming round cells, while fibroblastic cells, spreading in a monolayer over the periphery of nodules, were only weakly labeled. These findings indicate that OP might be expressed sequentially by chondrocytes and by cells that are transdifferentiating further and exhibit an osteocytic phenotype, and moreover, that expression of OP is closely associated with calcifying foci in the extracellular matrix.

Animals↗
PubMed1998

Collagenase-3 (MMP-13) expression in chondrosarcoma cells and its regulation by basic fibroblast growth factor.

Human collagenase-3 (MMP-13) is a member of the matrix metalloproteinase family of enzymes that was originally identified in breast carcinomas and subsequently detected during fetal ossification and in arthritic processes. In this work, we have found that collagenase-3 is produced by HCS-2/8 human chondrosarcoma cells. An analysis of the ability of different cytokines and growth factors to induce the expression of collagenase-3 in these cells revealed that basic fibroblast growth factor (bFGF or FGF-2) strongly up-regulated the expression of this gene. By contrast, other factors, including interleukin-1beta and transforming growth factor-beta, previously found to induce collagenase-3 expression in other cell types, did not exhibit any effect on the expression of this gene in chondrosarcoma cells. Further analysis of the bFGF-induced expression of collagenase-3 in human chondrosarcoma cells revealed that its effect was time and dose dependent, but independent of the de novo synthesis of proteins. Western blot analysis revealed that the up-regulatory effect of bFGF on collagenase-3 was also reflected at the protein level as demonstrated by the increase of immunoreactive protein in the conditioned medium of HCS-2/8 cells treated with bFGF. Immunohistochemical analysis of the presence of collagenase-3 in a series of 8 benign and 16 malignant cartilage-forming neoplasms revealed that all analyzed malignant chondrosarcomas stained positively for collagenase-3, whereas only 2 of 8 benign lesions produced this protease. In addition, the finding that bFGF was detected in all analyzed chondrosarcomas, together with the above in vitro studies on HCS-2/8 cells, suggest that this growth factor may be an in vivo modulator of collagenase-3 expression in these malignant tumors. These results extend the pattern of tumor types with ability to produce this matrix metalloproteinase and suggest that collagenase-3 upregulation may contribute to the progression of human chondrosarcomas.

Adolescent↗
PubMed1998

Peripheral type benzodiazepine receptor in T lymphocyte rich preparation.

Some types of mood disorders and drugs are suggested to affect peripheral type benzodiazepine receptors (PBR), but their mechanisms are unclear. The isolation of pure lymphocytes is requisite for the investigation of the function of PBR on lymphocytes, since platelets and monocytes also have many PBR. The objective of this study was to establish a method of binding assay for PBR using pure T lymphocytes. Mononuclear cells and T lymphocytes were prepared by using a density gradient material and magnetic beads, respectively. The cells were analyzed using flow cytometry and a counting chamber. Binding studies were performed using T lymphocytes from 10 normal volunteers. The T lymphocytes were incubated with [3H]PK11195, harvested on glass fiber filters, and counted with a plate scintillation counter. The binding data were analyzed by the Scatchard method. With the magnetic bead technique, pure T cells were selected that contained only 1.5% monocytes and platelet/cell ratio of 1.4. The Scatchard plot of the data indicated that only one type of specific binding site was involved in the binding. The dissociation constant (Kd) was 3.8+/-1.3nM (mean+/-SD), and the Bmax was 379+/-124 fmol//10(6) cells (mean+/-SD). The density gradient- magnetic beads technique can be used as an appropriate method of preparation of T cells for PBR binding assay.

Binding Sites↗
PubMed1998

Recurrent pemphigus vulgaris limited to the surgical area after mastectomy.

A 45-year-old Japanese female presented with bullae and erosions on the trunk in December 1987. The histologic findings revealed a suprabasal cleft and acantholytic cells. Immunofluorescence staining showed IgG autoantibodies in the intercellular spaces. With a working diagnosis of pemphigus vulgaris, she was treated successfully with low dosage prednisolone. Adenocarcinoma of the right breast was found in March 1994, and she received a mastectomy followed by breast reconstruction that used a transverse rectus abdominis muscle flap. Six months later, vesicobullous eruptions developed and were limited to the surgical area (right chest and abdomen). The histopathologic and direct immunofluorescence findings were consistent with pemphigus vulgaris. Although these skin lesions improved with high dosages of prednisolone, she died of multiple metastases due to the breast cancer.

Abdomen↗
PubMed1998

Bullous systemic lupus erythematosus: detection of antibodies against noncollagenous domain of type VII collagen.

A 9-year-old girl with systemic lupus erythematosus developed bullous eruption. Histopathologic examination showed subepidermal blistering and immunoglobulins (IgG, IgM, IgA) and complement components (C1q, C3) deposited linearly at the basement membrane zone. IgG in this patient's serum bound to the dermal side of 1 mol/L sodium chloride-split normal human skin, and a 290 kd protein was identified in the dermal extract. The patient's serum recognized various epitopes on the noncollagenous domain as demonstrated by the use of fusion proteins of type VII collagen. Resolution of the bullous eruption occurred after treatment with dapsone.

Antimetabolites↗
PubMed1998

Roxithromycin down-modulates antigen-presenting and interleukin-1 beta-producing abilities of murine Langerhans cells.

The immunomodulatory effect of the macrolide antibiotic, roxithromycin (RXM) on Langerhans cells (LC) was studied in mice. RXM inhibited the ability of LC to present superantigen and hapten to T cells at 100 microM. The superantigen-presenting activity of LC was more profoundly abrogated by RXM than the hapten-presenting activity. This functional reduction was partly attributed to an RXM-induced decrease in promotion of the expression of major histocompatibility complex class II molecules on LC. On the other hand, RXM down-modulated the production of interleukin-1 beta by LC at a lower concentration of 10 microM than concentrations that inhibited antigen presentation. These results imply that RXM exerts therapeutic effectiveness via not only bacteriocidal action but also inhibitory effect on the LC ability in T-cell-mediated cutaneous diseases that can be exacerbated by skin-colonized Staphylococcus aureus.

Animals↗
PubMed1998

Subcutaneous phaeohyphomycosis caused by Geniculosporium species; a new fungal pathogen.

A 70-year-old Japanese timberworker dealing with imported timber from the U.S.A. and Russia had an asymptomatic subcutaneous nodule with a small fistula on his left knee. Histopathological examination of the nodule revealed brownish hyphal elements in encapsulated pyogranuloma. The fungus isolated from a discharge of the fistula and an excised specimen of the lesion was identified as Geniculosporium sp., which represents a conidial state (anamorph) of several genera such as Anthostomella, Biscogniauxia, Euepixylon, Leprieuria, Nemania, Phylacia and Rosellina in the Xylariaceae. Whereas this dematiaceous hyphomycete is commonly found on decaying wood and bark of various trees, to our knowledge, this is the first case of a phaeomycotic cyst caused by fungi belonging to the genus Geniculosporium.

Aged↗
PubMed1998

8-hydroxydeoxyguanosine in urine as an index of oxidative damage to DNA in the evaluation of atopic dermatitis.

8-hydroxydeoxyguanosine (8-OHdG) is one of the products which are excreted in urine as a result of oxidative damage to DNA. We investigated the feasibility of using 8-OHdG in urine as an index for oxidative damage to DNA in atopic dermatitis (AD). Seventeen patients with long-standing AD and 17 healthy volunteers were enrolled in this study. The severity of AD was evaluated by SCORAD index. Eosinophils, total IgE and lactate dehydrogenase-5 in peripheral blood were measured as clinical parameters for AD. A newly developed enzyme-linked immunosorbent assay method was used to measure urine 8-OHdG. The AD patients showed significantly higher levels (P < 0.0001) of 8-OHdG in their urine than corresponding controls. Urine 8-OHdG levels showed as strong a positive correlation as other haematological parameters did using the SCORAD index. Thus, we conclude that the urine 8-OHdG levels can also serve as a biochemical index of tissue damage and can act as a useful tool in the clinical evaluation of AD.

8-Hydroxy-2'-Deoxyguanosine↗
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

Examination of the diagnostic value and estimation of the chaos phenomenon in masticatory movement using fractal dimension in patients with temporomandibular dysfunction syndrome.

The aim of this study was to estimate the chaos phenomenon (chaos) in masticatory movements using the fractal dimension (FD), and to examine the diagnostic value of the fractal dimension in comparing stomatognathic functional disturbances with normal stomatognathic function. The subjects were all high school students and included nine subjects presenting with acceptable normal occlusion, 18 subjects with TMJ dysfunction syndrome and seven subjects with tooth crowding. Masticatory movements were obtained during free, right side, and left side gum-chewing and were used to calculate the capacity dimension in the FD. Chaos in the masticatory movement was estimated by the FD saturated with some constant value to an increase of embedding dimension (approached a plateau). In the crowding group, the FD was also significantly high on the sagittal plane in comparison with the normal. In the patients with pain, the FD on the sagittal plane was significantly high. In the patients with pain and closed lock, the FD on the frontal plane was significantly high. However, in the patients with pain and with reduction of anterior disc displacement, the FD was significantly low on the horizontal plane. These findings suggest that chaos is present in masticatory movements and the difference in the FD are of diagnostic value in evaluation of the relationship between FD and stomatognathic functional disturbance.

Adolescent↗