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Biomedical subjects

M Takigawa

Publications and source records attributed to M Takigawa.

At least 73 records · Page 4Linked to original sources
PubMed2001

Lupus erythematosus profundus with unusual skin manifestation: subcutaneous nodules coexisting with eyelid plaques.

A 71-year-old Japanese woman presented with erythematous plaques on the eyelids and subcutaneous indurations or nodules with or without overlying erythema on the hands, thigh, and leg. She also had oral ulcers, arthralgia and a low grade fever. Laboratory tests revealed an elevated titer of antinuclear antibody, an increased erythrocyte sedimentation rate and anemia. Skin biopsy specimens from the hand and thigh showed lymphocytic perivascular and periappendageal infiltrates and vacuolar alterations at the basement membrane zone of the skin appendages. Moreover, there was a dense lymphocytic infiltrate deep in the dermis with extension into the subcutaneous fat, which was compatible with the diagnosis of lupus erythematosus profundus. Although the biopsy specimen from the eyelid lesion did not contain the subcutaneous fat, the changes in the dermis were essentially the same as those of the hand and thigh. The eruption as well as the other symptoms promptly responded to oral prednisolone.

Aged↗
PubMed2001

Percutaneous peptide immunization via corneum barrier-disrupted murine skin for experimental tumor immunoprophylaxis.

Percutaneous peptide immunization is a method in which tumor-specific cytotoxic T lymphocytes (CTL) are primed in the lymph nodes and spleen following application of tumor peptides to corneum barrier-disrupted murine skin. Immunized mice are protected against subsequent challenge with corresponding tumors and suppress the growth of established tumors. CTL expansion after peptide application seems to be mediated by epidermal Langerhans' cells. In the human, disruption of permeability barrier by tape stripping also induces activation of epidermal Langerhans' cells. Thus, percutaneous peptide immunization provides a simple and noninvasive means of inducing potent antitumor immunity that may be exploited for cancer immunotherapy in the human.

Administration, Cutaneous↗
PubMed2001

Photoactivational cytokine-modulatory action of 8-methoxypsoralen plus ultraviolet A in lymphocytes, monocytes, and cutaneous T cell lymphoma cells.

Treatment with 8-methoxypsoralen (8-MOP) and ultraviolet A light (UVA) has been reported to modulate cytokine production in various cells. Our study was conducted to see the effects of 8-MOP/UVA on the expression/production of cytokines in peripheral blood lymphocytes and monocytes in relation to the therapeutic mechanisms of extracorporeal photochemotherapy. 8-MOP/UVA augmented the expression of mRNAs for interferon-gamma (IFN-gamma) and interleukin (IL)-2 and reduced those for IL-4 and IL-10 in peripheral blood mononuclear cells (PBMCs) from normal subjects and Sézary syndrome patients. This enhancement of Th1 cytokines was caused by increment of cytokine production by Th1 cells but not by conversion of Th2 cells to produce Th1 cytokines. The number of IFN-gamma-secreting lymphocytes was markedly increased in 8-MOP/UVA-treated PBMCs 20 h after treatment, and its amount was elevated in culture supernatants. However, this enhanced production of IFN-gamma was found only until three days after 8-MOP phototreatment, and its level was rapidly declined by five days after treatment. In addition to this Th1-polarized action, 8-MOP/UVA-treated PBMCs produced enhanced amounts of IL-8 upon stimulation with anti-CD3/CD28 antibodies. Phototreated CD4+ but not CD8+ cells provided excellent T cell help for monocytes to produce IL-8 via a direct cell-to-cell contact mechanism. These findings suggest that 8-MOP/UVA has a transient but biologically active Th1-skewing action in T cells, and the phototreated T cells simultaneously stimulate monocytes to produce IL-8. It is suggested that 8-MOP/UVA exerts a beneficial therapeutic effect on malignant Th2 neoplasms as a Th1-skewing cytokine modifier and that 8-MOP-phototreated CD4+ T cells allow monocytes to become effective tumor antigen-presenting cells for tumor-specific cytotoxic T cells.

Cytokines↗
PubMed2001

Recognition of YKL-39, a human cartilage related protein, as a target antigen in patients with rheumatoid arthritis.

OBJECTIVE: To investigate whether autoimmunity to YKL-39, a recently cloned cartilage protein, occurs in patients with rheumatoid arthritis (RA). METHODS: Autoantibody to YKL-39 was assayed by enzyme linked immunosorbent assay (ELISA) and western blotting in serum samples from patients with RA, systemic lupus erythematosus (SLE), and healthy donors, using recombinant YKL-39 protein. This reactivity was compared with that against a YKL-39 homologue, YKL-40 (human cartilage gp-39/chondrex), which has been reported to be an autoantigen in RA. RESULTS: Autoantibody to YKL-39 was detected in seven of 87 patients with RA (8%), but not in serum samples from patients with SLE or healthy donors. YKL-40 reactivity was found in only one of 87 RA serum samples (1%), with no cross reactivity to YKL-39. CONCLUSION: The existence of anti-YKL-39 antibody in a subset of patients with RA is reported here for the first time. Further, it was shown that the immune response to YKL-39 was independent of that to YKL-40. Clarification of the antibody and T cell responses to autoantigens derived from chondrocyte, cartilage, or other joint components may lead to a better understanding of the pathophysiology of joint destruction in patients with RA.

Adipokines↗
PubMed2001

Involvement of CTGF, a hypertrophic chondrocyte-specific gene product, in tumor angiogenesis.

Connective tissue growth factor (CTGF) is a potent secreted signaling factor which functions in multiple stages of angiogenesis. In the present study, we examined the role of CTGF in tumor angiogenesis and made the following observations: (1) Histological analysis of human breast cancer (MDA231) cell and human fibrosarcoma (HT1080) cell xenografts in BALB/c nude mice showed a high level of neovascularization. Human squamous cell carcinoma (A431) xenografts induced only a low level of neovascularization. (2) CTGF mRNA was strongly expressed in MDA231 and in HT1080 cells in vivo and in vitro, but not in A431 cells. (3) CTGF protein was markedly produced in MDA231 cells and HT1080 cells and secreted into culture medium, and its production was greater during phases of growth rather than confluency. (4) Production of CTGF in bovine aorta endothelial cells was induced by CTGF, VEGF, bFGF and TGF-beta. (5) Neovascularization induced by HT1080 cells or MDA231 cells on chicken chorioallantoic membrane was suppressed in the presence of neutralizing CTGF-specific polyclonal antibody. These results suggest that CTGF regulates progression in tumor angiogenesis and the release or secretion of CTGF from tumor cells is essential for the angiogenesis.

Allantois↗
PubMed2001

Mechanical stimulation induces CTGF expression in rat osteocytes.

Connective tissue growth factor (CTGF), which is encoded by an immediate early gene and a member of the CCN family, has been shown to be expressed in osteoblasts, fibroblasts, and chondrocytes. Although CTGF is expressed in bone and cartilage tissues, we tested the hypothesis that CTGF is regulated in mechanotransduction. In the alveolar bone during experimental tooth movement, CTGF mRNA was expressed in osteoblasts and in osteocytes localized around the periodontal ligament under control conditions. Interestingly, 12 hrs after the start of experimental tooth movement, the expression of CTGF mRNA in osteocytes and osteoblasts became more intense around the periodontal ligament, and the intense expression of CTGF extended to osteocytes situated deep in alveolar bone matrix apart from periodontal ligament in both tension and compression sides. Our present findings indicate that CTGF could play a role in regulation of osteocyte function during the mechanical stimulation of bone.

Alveolar Process↗
PubMed2001

Mitogenic effects of neutrophins on a periodontal ligament cell line.

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) are three representative neurotrophins responsible for the differentiation and survival of neurons, and their high-affinity receptors are tropomyosin-receptor-kinase (TRK)A, TRKB, and TRKC, respectively. In this study, we investigated the expression of neurotrophins in a mouse periodontal ligament cell line (MPL), by reverse transcription-polymerase chain-reaction (RT-PCR) and enzyme-linked immunoabsorbent assay (ELISA). We also studied the expression of TRK receptors on MPL by immunostaining and the effects of neurotrophins on the proliferation of MPL, with a hypothesis of autocrine mechanism of neurotrophins. Each neurotrophin and TRK receptor was expressed, and neurotrophins enhanced the proliferation of MPL. These findings suggest that the MPL has functional neurotrophin receptors involved in an autocrine function of neurotrophins. The expression level of neurotrophins and TRKs showed the reverse pattern, and we propose an auto-regulatory mechanism of ligands and receptors in accordance with the level of synthesized neurotrophins.

Alkaline Phosphatase↗
PubMed2001

Type II alveolar epithelial cells and interstitial fibroblasts express connective tissue growth factor in IPF.

Connective tissue growth factor (CTGF) is a growth and chemotactic factor for fibroblasts encoded by an immediate early gene that is transcriptionally activated by transforming growth factor-beta. Previous studies have shown that both CTGF messenger ribonuclear acid (mRNA) and protein are expressed in renal fibrosis and bleomycin-induced pulmonary fibrosis in mice. The aim of the present study was to investigate the localization of CTGF protein and its mRNA expression in the fibrotic lung tissue of patients with idiopathic pulmonary fibrosis (IPF). Using human fibrotic lung tissue obtained from eight autopsy cases and four biopsy cases with IPF, immunohistochemical staining, in situ hybridization, and reverse transcription-polymerase chain reaction (RT-PCR) were performed. The cellular immunoreactivity for CTGF was markedly increased in the lung tissue of patients with IPF, compared to normal lungs. The immunolocalization of CTGF was confined predominantly to proliferating type II alveolar epithelial cells and activated fibroblasts. In the normal lung, type II alveolar epithelial cells stained for CTGF were sparsely distributed. CTGF mRNA was localized in proliferating type II alveolar epithelial cells and activated fibroblasts in the interstitium of fibrotic lung tissues. RT-PCR analysis showed that CTGF mRNA was expressed at a higher level in fibrotic lungs than in normal lungs. In both an autocrine and a paracrine manner, type II alveolar epithelial cells and activated fibroblasts may play a critical role in pulmonary fibrosis by producing connective tissue growth factor which modulates fibroblast proliferation and extracellular matrix production.

Adult↗
PubMed2001

Tumor necrosis factor alpha induces expression of genes for matrix degradation in human chondrocyte-like HCS-2/8 cells through activation of NF-kappaB: abrogation of the tumor necrosis factor alpha effect by proteasome inhibitors.

Tumor necrosis factor alpha (TNF-alpha) has been suggested to induce chondrocytic chondrolysis in both inflammatory and degenerative joint diseases. However, its intracellular signaling pathway leading to the chondrolysis has not been studied in detail. Thus, we investigated whether TNF-alpha activates a transcription factor nuclear factor kappaB (NF-kappaB) in human chondrocyte-like cells (HCS-2/8) and induces the expression of genes involved in the degradation of cartilage matrix. Treatment of the cells with TNF-alpha markedly increased the levels of matrix metalloproteinase 1 (MMP-1), MMP-3, intercellular adhesion molecule 1 (ICAM-1), and cyclo-oxygenase 2 (COX-2) messenger RNAs (mRNAs). The increase in the mRNAs was associated with the activation of p65/p50 heterodimer NF-kappaB. IkappaB-alpha and IkappaB-beta, cytoplasmic molecules preventing the nuclear translocation of NF-kappaB, were degraded rapidly by TNF-alpha followed by their synthesis to the basal level. Treatment with proteasome inhibitors inhibited the degradation of both IkappaB-alpha and IkappaB-beta and prevented the TNF-alpha-dependent nuclear translocation of p65. Furthermore, the inhibitors completely prevented the TNF-alpha-dependent induction of MMP-1, MMP-3, ICAM-1, and COX-2 mRNAs. Thus, it is shown that the activation of p65/p50 NF-kappaB by TNF-alpha plays a cardinal role in inducing the expression of MMP-1, MMP-3, ICAM-1, and COX-2 genes, which are involved in matrix degradation and inflammatory reaction in chondrocytes, leading to chondrocytic chondrolysis.

Blotting, Western↗
PubMed2001

Vegetarian diet ameliorates symptoms of atopic dermatitis through reduction of the number of peripheral eosinophils and of PGE2 synthesis by monocytes.

Many patients with atopic dermatitis are dissatisfied with conventional treatments based on topical steroids and have experienced some traditional remedies and alternative therapies. However, most of such therapies have not been evaluated scientifically and clinically by specialists. This study was designed to assess whether a certain vegetarian diet might be effective for atopic dermatitis and if so, to identify the mechanisms of this remedy through analyses of immunological parameters. An open-trial study was carried out in twenty patients with atopic dermatitis. An improvement of dermatitis was evaluated by SCORAD index and serological and immunological parameters were monitored. After a two-month treatment, the severity of dermatitis was strikingly inhibited, as assessed by SCORAD index and serological parameters including LDH5 activity and a number of peripheral eosinophils. A sharp reduction in eosinophils and neutrophils was observed prior to improvement in the skin inflammation. In addition, PGE2 production by peripheral blood mononuclear cells was reduced by this treatment. In contrast, serum IgE levels did not change during the same period. Although this study is an open-trial one, it suggests that this treatment may be useful for the treatment of adult patients with severe atopic dermatitis.

Adolescent↗
PubMed2001

Expression of transduced HSP70 gene protects chondrocytes from stress.

OBJECTIVE: To investigate the efficacy of adenovirus vector mediated transduction of heat shock protein 70 (HSP70) gene to human chondrocyte-like cell (HCS-2/8) against heat stress. METHODS: Two adenovirus vectors that contain wild-type (AxSHEwt) or mutant-type (AxSHEmt) HSP70 gene, and that are regulated by SRalpha promoter, were constructed. The mutant-type lacks the area that expresses stress durability. One of the 2 adenovirus vectors was added to the cultures of human chondrocyte-like cells (HCS-2/8). Heat stress (48 degrees C) was applied to the transduced cells for 2 h, and the efficacy of adenovirus vector mediated transduction of HSP70 gene against heat stress in the chondrocytes was investigated using alamar blue assay and MTT assay. RESULTS: Absorbance levels at 48 degrees C were 300.3 +/- 51.9 and 1.173 +/- 0.011 in the controls, 278.5 + 33.8 and 1.217 +/- 0.018 in the AxSHEmt transduced cells, and 349 +/- 14.7 and 1.371 +/- 0.033 in the AxSHEwt transduced cells. The level in the AxSHEwt transduced cells was significantly higher than in the other 2 groups (p < 0.05). With 37 degrees C treatment, no significant difference was observed. CONCLUSION: Chondrocytes to which HSP70 gene was transduced had a significantly higher metabolic activity and viability under heat stress.

Adenoviridae↗
PubMed2001

[Evaluation of the conjunctiva of leprosy patients using impression cytology].

OBJECTIVE: To evaluate ocular surface disorders (OSD) similar to cicatricial pemphigoid in leprosy patients. SUBJECT AND METHOD: Sixteen leprosy patients were examined. They were under treatment as inpatients at the Tama Zenshoen National Sanatorium, an institution for the treatment of leprosy. In addition to routine ophthalmological examinations, the patients conjunctival goblet cells were examined using impression cytology. OSD similar to ocular cicatricial pemphigoid were defined as the presence of at least two items of the following: symblepharon, cicatricial contraction of the conjunctival sac, corneal neovascularization, and palpebral entropion. RESULTS: OSD was present in 8 of the 16 patients (50%). Goblet cells were either decreased in number or absent in 7 cases(44%), and included 4 cases with OSD. Six of the 7 cases(86%) with reduced or absent goblet cells had been diagnosed as leprosy prior to 1944. CONCLUSION: Reduction or absence of goblet cells is a frequent feature in leprosy patients, particularly in longstanding ones of 56 years or more. Insufficient initial treatment appears to be a major cause of this finding.

Aged↗
PubMed2000

Characterization of a mouse ctgf 3'-UTR segment that mediates repressive regulation of gene expression.

We isolated a small segment of the 3'-untranslated region (3'-UTR) in the mouse connective tissue growth factor (ctgf/fisp12) gene and evaluated its functionality. Comparison of the nucleotide sequences of human and mouse ctgf 3'-UTRs revealed a conserved small segment of 91 bases. The corresponding segments of the 3'-UTRs shared as much as 82.4% homology, whereas the overall homology between the 3'-UTRs was 71.8%. To study the functionality of the conserved segment, the corresponding region of mouse ctgf cDNA was amplified from NIH3T3 cells. When it was fused downstream of a marker gene, it showed remarkable repressive effects on gene expression. The repressive effect of the sense form was more prominent than that of the antisense form. Computer analyses of these sequence predicted stable secondary structures, suggesting that they act at the RNA level. The predicted structures of the sense and antisense forms appeared to be slightly different, which is consistent with the difference in repressive function. These findings defined the conserved small element in the mouse ctgf gene as a potent negative regulator of gene expression, which may act at a posttranscriptional level.

3' Untranslated Regions↗
PubMed2000

Expression of connective tissue growth factor in cartilaginous tumors.

BACKGROUND: Connective tissue growth factor (CTGF) predominantly is expressed in hypertrophic chondrocytes and its specific receptors are demonstrated on chondrocytic cells. Therefore, CTGF may be involved in the proliferation and/or differentiation of cartilage cells. In the current study, CTGF expression was examined both in chondrosarcoma and enchondroma to clarify the relation between the expression of CTGF and the grade of malignancy. METHODS: The expression of CTGF and proliferating cell nuclear antigen (PCNA) were analyzed immunohistochemically in 34 cartilaginous tumor specimens. Eighteen tumors were determined to be chondrosarcoma including 8 Grade 1 tumors, 6 Grade 2 tumors, and 4 Grade 3 tumors. The percentage of CTGF positive and PCNA positive cells was quantified using at least 500 cells. RESULTS: CTGF was expressed in 70.1% of enchondroma cells, 84.0% of Grade 1 chondrosarcoma cells, 53.7% of Grade 2 tumor cells, and 26.8% of Grade 3 tumor cells (rho = -0.501; P = 0.0053). In chondrosarcoma cases, CTGF expression was correlated closely with tumor grade (rho = -0.920; P = 0.0001). There was a strong correlation between PCNA expression and tumor grade (rho = 0.907; P < 0.0001) and a strong negative correlation between CTGF and PCNA expression (rho = -0.493; P = 0.0061). In chondrosarcoma cases, patients with high expression of CTGF (>/= 30%) showed higher overall survival compared with those with low expression (< 30%) (P = 0.004). CONCLUSIONS: The current study revealed a correlation between the histologic grade of chondrosarcoma and prognosis, and the concomitant association between CTGF immunostaining and tumor grade and prognosis. Therefore, immunohistochemical staining with CTGF is a useful procedure for assessing the tumor grade and clinical course in patients with chondrosarcoma.

Adolescent↗
PubMed2000

Identification of an RNA element that confers post-transcriptional repression of connective tissue growth factor/hypertrophic chondrocyte specific 24 (ctgf/hcs24) gene: similarities to retroviral RNA-protein interactions.

The repressive effect of the 3'-untranslated region (3'-UTR) in human connective tissue growth factor/ hypertrophic chondrocyte specific 24 (ctgf/hcs24) mRNA on gene expression had been demonstrated in our previous study. Here, we identified a minimal RNA element in the 3'-UTR, which acts as a cis-acting element of structure-anchored repression (CAESAR). Deletion analyses of the 3'-UTR led us to minimize the element of 84 bases at the junction of the coding region and the 3'-UTR. The minimized RNA segment is predicted, and actually capable of forming a stable secondary structure in vitro. Mutational analyses disclosed a significant relationship between the predicted structure and repressive effect. The utility of CAESAR as a post-transcriptional regulatory element was represented by the fact that steady-state mRNA levels were not affected by CAESAR linked in cis, while protein levels from such a chimeric gene were markedly reduced. Of note, the CAESAR sequence exerted no effect, when it was placed upstream of the promoter. Finally, RNA gel electromobility-shift analyses demonstrated a nuclear factor that interacts with the folded CAESAR. Taken together, it was uncovered that CAESAR of ctgf is a novel post-transcriptional structured RNA regulatory element, probably acting through direct interactions with a nuclear factor as observed in retroviral RNA elements with certain proteins.

3' Untranslated Regions↗