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Biomedical subjects

T Kadono

Publications and source records attributed to T Kadono.

At least 37 records · Page 2Linked to original sources
PubMed1997

Circulating intercellular adhesion molecule-1 in the sera of patients with systemic sclerosis: enhancement by inflammatory cytokines.

We measured serum levels of circulating intercellular adhesion molecule-1 (cICAM-1) in patients with systemic sclerosis (SSc) and normal controls. The levels of cICAM-1 were determined by sandwich enzyme-linked immunosorbent assay in sera from 88 patients with SSc and in 20 healthy controls. In addition, these levels were examined in the supernatants of cultured peripheral blood mononuclear cells (PBMC) and dermal fibroblasts from 10 patients with SSc and 10 healthy control subjects. Serum levels of cICAM-1 were significantly higher in patients with SSc than in healthy controls. Serum cICAM-1 levels were significantly higher in patients with diffuse cutaneous SSc (dcSSc) than in patients with limited cutaneous SSc (lcSSc). These serum levels were correlated with the presence of contracture of phalanges, pulmonary fibrosis, joint involvement and increased erythrocyte sedimentation rate. The release of cICAM-1 was significantly increased in the supernatants of cultured PBMC from patients with SSc. Moreover, inflammatory cytokines (interferon-gamma, interleukin-1 and tumor necrosis factor-alpha) enhanced the release of cICAM-1 in vitro in SSc cells. These findings suggest that cICAM-1 may be involved in immune reactions in this disease.

Cells, Cultured↗
PubMed1997

Tissue inhibitor of metalloproteinase 1 (TIMP-1) may be an autocrine growth factor in scleroderma fibroblasts.

In scleroderma (systemic sclerosis, SSc), an autoimmune disorder in which excessive extracellular matrix is deposited in skin and internal organs, one of the suggested contributory factors to the development of fibrosis is a decrease in collagenase activity that may be related to levels of serum tissue inhibitors of metalloproteinases 1 (TIMP-1). We recently reported that the serum TIMP-1 levels in SSc patients were elevated compared with normal controls. To determine the biologic significance of TIMP-1 in SSc, we compared the proliferative effects of TIMP-1 between normal and SSc fibroblasts. TIMP-1 showed significant mitogenic activity for both normal and SSc fibroblasts. The mitogenic responses to TIMP-1 (33-100 ng/ml) in SSc fibroblasts, however, were significantly greater than those in normal controls and were completely neutralized in the presence of anti-TIMP-1 IgG. Moreover, anti-TIMP-1 IgG partially but significantly blocked the basal mitogenic activities of SSc fibroblasts. SSc fibroblasts produced increased amounts of TIMP-1 relative to normal fibroblasts, as confirmed by western blotting, ELISA, and RT-PCR techniques. In contrast, transforming growth factor beta1 (TGF-beta1) upregulated TIMP-1 production in normal fibroblasts but not in SSc fibroblasts with elevated spontaneous secretion of TIMP-1. These observations suggest that TIMP-1 may play an important role as an autocrine growth factor in the fibrotic process in SSc.

Female↗
PubMed1996

Decreased ET(B) receptor expression in human metastatic melanoma cells.

In this study, we examined the endothelin (ET) receptor subtype involved in mitogenic signaling in human primary and metastatic melanoma cell lines. In a reverse transcriptase-polymerase chain reaction (RT-PCR) study, ET(B) mRNA expression in metastatic melanoma cells was decreased from that of primary melanoma. Only RPM-EP, a primary recurrent melanoma cell line, showed strong ET(A) mRNA expression. ET-1 and ET-3 stimulated DNA synthesis of primary and recurrent cutaneous melanoma cells in serum-deprived cultures. The growth response to ET-1 in metastatic melanoma cells was decreased from that in primary melanoma cells. [125I]-IRL-1620 binding to PM-WK, a primary melanoma cell line, was significantly blocked by excessive amounts of unlabeled BQ-788. [125I]-IRL-1620 binding to metastatic melanoma cells was significantly decreased from that of primary melanoma cells. From these results, we conclude that the mitogenic effects of ET in human primary melanoma are mainly mediated through ET(B) receptors and that down-regulation of ET(B) receptors causes the decreased growth response of ET-1 in metastatic melanoma cells.

Amino Acid Sequence↗
PubMed1996

Serum concentrations of basic fibroblast growth factor in collagen diseases.

BACKGROUND: Basic fibroblast growth factor (bFGF), a cytoplasmic polypeptide growth regulator that induces endothelial cell and fibroblast proliferation, is produced by endothelial cells and skeletal muscle. OBJECTIVE: We hypothesized that this factor is involved in fibrotic changes in muscle and skin in collagen diseases. METHODS: The serum level of bFGF was measured in 74 patients with systemic sclerosis, 12 with systemic lupus erythematosus, 33 with dermatomyositis, 13 with Raynaud's disease, and 20 control subjects. RESULTS: bFGF was undetectable in the serum of normal persons, but detectable levels were found in 31 of 74 patients with systemic sclerosis and 7 of 33 patients with dermatomyositis. Elevated serum bFGF level was correlated with an elevated plasma endothelin level and anticentromere antibody in patients with systemic sclerosis. An elevated serum bFGF level correlated with lung fibrosis and an elevated creatine kinase level in the patients with dermatomyositis. CONCLUSION: Measurement of the serum bFGF level may be useful to detect vascular damage in patients with systemic sclerosis and muscule fibrosis in patients with dermatomyositis.

Adolescent↗
PubMed1995

Impaired growth response to endothelin-1 in scleroderma fibroblasts.

Systemic sclerosis (SSc) is characterized by vascular damage and dermal fibrosis. In this study, we examined the endothelin (ET) receptor subtype involved in mitogenic signaling in scleroderma and normal skin fibroblasts. ET-1 stimulated DNA synthesis of normal fibroblasts in serum-deprived cultures. ET-3 had lesser effects on DNA synthesis of normal fibroblasts than ET-1. The growth response to ET-1 in scleroderma fibroblasts was decreased compared to normal fibroblasts. [125I]-ET-1 binding to normal fibroblasts was significantly blocked by excessive amount of unlabeled ET-1 and BQ-123. [125I]-ET-1 binding to scleroderma fibroblasts was significantly decreased compared with normal controls. Immunoblotting analysis showed that the expression of ETA receptor in scleroderma fibroblasts was diminished compared with normal controls. ETA mRNA expression in scleroderma fibroblasts was decreased compared with that of normal fibroblasts. From these results, we conclude that the mitogenic effects of ET in human dermal fibroblasts are mainly mediated through ETA receptors, and that down-regulation of ETA receptors caused the decreased growth response of ET-1 in scleroderma fibroblasts.

Biopsy↗
PubMed1995

Elevated plasma endothelin levels in systemic sclerosis.

Endothelin is a novel potent vasoconstrictor peptide produced mainly by endothelial cells. Thrombomodulin is a high-affinity thrombin receptor on vascular endothelial cells that plays an important role as a natural anticoagulant. In this study, we measured plasma levels of endothelin and thrombomodulin in patients with systemic sclerosis or Raynaud's disease. Plasma levels of endothelin and the ratio of thrombomodulin to creatinine were significantly increased in patients with systemic sclerosis compared with normal controls, and there was a positive correlation between these two indicators (r = 0.615, P = 0.004). Moreover, plasma levels of endothelin were significantly higher in patients with diffuse systemic sclerosis than in patients with limited systemic sclerosis. In contrast, plasma levels of endothelin in patients with Raynaud's disease were not significantly increased. These results suggest that increased plasma levels of endothelin and thrombomodulin may reflect microvascular damage in systemic sclerosis.

Adult↗
PubMed1995

Growth regulation in scleroderma fibroblasts: increased response to transforming growth factor-beta 1.

We investigated the responses of normal and scleroderma fibroblasts to various growth factors, especially transforming growth factor-beta 1 (TGF-beta 1). The effects of various growth factors on [3H]thymidine incorporation in normal and scleroderma fibroblasts were examined. [125I]-labeled platelet-derived growth factor (PDGF)-BB binding in scleroderma and normal fibroblasts was examined both in the presence and absence of TGF-beta 1 (1 ng/ml). Cytoplasmic protein was isolated and analyzed by Western blotting. Total RNA from fibroblasts was also isolated and analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) using specific primer sets. Mitogenic responses to TGF-beta 1 (0.33-1 ng/ml) in seven scleroderma fibroblast strains were significantly greater than those in normal controls. [125I]-PDGF-BB binding to scleroderma fibroblasts was increased after TGF-beta 1 stimulation. The increased response to TGF-beta 1 was shown to be mediated through PDGF-like protein induction; TGF-beta 1-treated scleroderma fibroblasts produced greater amounts of 36-kD PDGF-like protein, which was reported previously as connective tissue growth factor (CTGF), than did TGF-beta 1-treated normal fibroblasts. TGF-beta 1 treatment also upregulated PDGF-alpha receptor expression in scleroderma fibroblasts but not in normal dermal fibroblasts. mRNA expression of CTGF and PDGF-alpha receptor was correlated with the above protein expression. These observations suggest that the increased growth response to TGF-beta 1 in scleroderma fibroblasts is mediated through the induction of CTGF and PDGF-alpha receptor.

Cell Division↗
PubMed1995

Effects of various growth factors and histamine on cultured keloid fibroblasts.

OBJECTIVE AND METHODS: We investigated the effects of several growth factors on [3H]thymidine incorporation and procollagen type I carboxyterminal propeptide (P1CP) production, which reflects type I collagen metabolism, in keloid and normal fibroblasts. RESULTS: Six fibroblast cell strains, derived from keloid or normal skin, exhibited similar growth responses to platelet-derived growth factor, transforming growth factor beta 1 (TGF-beta 1), gamma-interferon (gamma-IFN) and histamine. In contrast, keloid fibroblasts showed significantly greater growth response to epidermal growth factor (EGF) than normal fibroblasts. P1CP production was 4.4 times higher in 6 strains of keloid fibroblasts than in 6 controls. Treatment with gamma-IFN (100 U/ml) decreased P1CP production in both groups; the effect was significantly greater in keloid fibroblasts. TGF-beta 1 treatment upregulated P1CP production in both groups. Treatment with histamine increased P1CP production in keloid fibroblasts, although it did not change that in the controls. CONCLUSION: EGF and histamine may play some role in the development of keloids.

Cell Division↗
PubMed1995

Elevated procollagen type I carboxyterminal propeptide production in cultured scleroderma fibroblasts.

BACKGROUND: We recently reported that the serum concentration of procollagen type I carboxyterminal propeptide (P1CP) in patients with systemic sclereosis (SSc) was elevated. In the present study, we investigated collagen metabolism in in vitro cultured scleroderma fibroblasts by measuring P1CP levels in the culture medium. METHODS AND RESULTS: Spontaneous P1CP production was 4.2 times higher in fibroblast cultures from patients with SSc (n = 11) than in those from healthy controls (n = 10). P1CP production in fibroblasts derived from diffuse cutaneous SSc patients was significantly greater than that from limited cutaneous SSc patients. The serum P1CP level in SSc patients was correlated with the P1CP production of cultured fibroblasts (r = 0.815, p < 0.005). Transforming growth factor beta increased P1CP production, and gamma-interferon decreased P1CP production similarly in both SSc and normal fibroblasts. In contrast, histamine dihydrochloride increased P1CP production only in SSc fibroblasts but not in controls. CONCLUSION: These findings suggest that P1CP production in SSc fibroblasts is relevant to in vivo collagen synthesis in SSc patients.

Adolescent↗
PubMed1994

The growth regulation of neurofibroma cells in neurofibromatosis type-1: increased responses to PDGF-BB and TGF-beta 1.

In neurofibromatosis type-1 (NF-1), abnormal growth regulation may be related to the formation of multiple neurofibromas. We investigated the growth responses of neurofibroma-derived cells (NF cells) and control skin fibroblasts to various growth factors. The responses to platelet-derived growth factor (PDGF-BB) and transforming growth factor-beta 1 (TGF-beta 1) in NF cells were significantly greater than those in control fibroblasts. The increased response to PDGF-BB in NF cells was accompanied by an increased number of PDGF beta receptors, which was demonstrated by both 125I PDGF-BB binding assay and immunoblotting analysis. The increased response to TGF-beta 1 was assumed to be mediated through PDGF-like protein induction; TGF-beta 1-treated NF cells produced greater amounts of 36-kD PDGF-like protein than TGF-beta 1-treated control fibroblasts. These observations suggest that certain growth factors, e.g., PDGF-BB and TGF-beta, may play some role in the development of neurofibromas in NF-1.

Becaplermin↗
PubMed1994

Serum concentration of procollagen type I carboxyterminal propeptide in localized scleroderma.

BACKGROUND AND DESIGN: Recently, we reported that the serum procollagen type I carboxyterminal propeptide (P1CP) level of patients with systemic sclerosis was elevated and correlated with disease severity. In this study, the serum level of P1CP was measured using the enzyme-linked immunosorbent assay in 39 patients with localized scleroderma and in 30 control subjects. RESULTS: The mean P1CP level in the patients was significantly higher than that in the normal control subjects. In 30% of the patients with localized scleroderma, the serum P1CP level was considered to be elevated (> 305 ng/mL; ie, 2 SDs above the mean control value). The mean serum P1CP level in the patients with generalized morphea was significantly higher than in the patients with morphea or linear scleroderma. In addition, the serum P1CP level in the patients with localized scleroderma was correlated with the number of sclerotic lesions, and it was negatively correlated with the duration of the disease. Anti-single-stranded DNA antibody and antihistone antibody were detected significantly more frequently in the patients with elevated P1CP than in the patients with normal P1CP. CONCLUSION: These findings suggest that the serum P1CP level is a useful indicator of disease severity in patients with localized scleroderma, as it has been found to be in those with systemic sclerosis.

Adolescent↗
PubMed1993

Dermatofibrosarcoma protuberans: increased growth response to platelet-derived growth factor BB in cell culture.

Dermatofibrosarcoma protuberans (DFSP) is a malignant tumor originating in the dermis. Although it is locally aggressive and recurs unless completely excised, it only rarely metastasizes. In the present study, we established 4 cultured DFSP cell strains, which were almost identical to normal skin fibroblasts when observed under a phase-contrast-microscope, and we observed their responses to various growth factors. DFSP cells showed significantly greater response to platelet-derived growth factor BB(PDGF BB) and transforming growth factor beta 1(TGF beta 1) than normal fibroblasts. We also determined upregulation of PDGF beta receptors in DFSP cells by both 125I PDGF-BB binding assay and immunoblotting analysis. These findings suggest that the interaction between the PDGF-B chain and the overexpression of PDGF beta receptors might play a role in the development of DFSP tumors.

Cell Division↗
PubMed1989

[Transplantable osteosarcomas in rats. I. The growth behavior of spontaneous and 4-HAQO induced osteosarcomas in rats].

While there are a number of experimental animal models for osteosarcoma development, the available rat systems are limited both in number and applicability. The present report concerns our attempts to establish an appropriate rat model to allow development of new experimental approaches to human osteosarcoma. A spontaneously occurring osteosarcoma (J. H. 1-OS) was found in a 35 week old male rat. The tumor could be transplanted and grew well and although the bone forming activity decreased after the 18th generation, the growth potential remained high.

4-Hydroxyaminoquinoline-1-oxide↗
PubMed1986

The developmental changes of the extracerebral space seen on ultrasonography in neonates and infants.

Ultrasonographic examination was performed in 70 healthy neonates and infants using a real-time sector scanner array machine with a 7.5-MHz transducer and a 4 cm waterbag. The skin, subcutaneous tissue, dura mater, interhemispheric fissure, gyri, sulci and sagittal sinus could be clearly visualized on ultrasonography (US), and the distance from the dura mater to the brain surface was determined. The extracerebral space under the anterior fontanel increased until 3 months after birth, and decreased gradually from 3 months to 12 months. The width and structure of the extracerebral space seen on US can be useful as parameters for assessing the process of brain growth and for detecting extra- and intracerebral pathologies in neonates and infants.

Brain↗
PubMed1982

Induction of immunological tolerance to single-stranded and double-stranded DNA.

Single-stranded (ss) and double-stranded (ds) DNA were conjugated with the copolymers of d-glutamic acid and d-lysin (d-GL). Administration of ss-DNA-d-GL conjugates to C3H/H3 and NZB/W F1 mice could render the mice tolerant to both direct and indirect anti-ss-DNA antibody-forming cell responses, irrespective of their immune status. Repeated administration of ss-DNA- or ds-DNA-d-GL conjugates decreased the levels of anti-ss-DNA and anti-ds-DNA antibody titres and reduced the occurrence of ss-DNA and ds-DNA antibody-forming cells even in old female NZB/W F1 mice that had already developed an autoimmune state with lupus nephritis. The unresponsiveness was DNA-specific, and the state of tolerance was stable in vitro at the cellular level after the removal of the tolerogen. This tolerance model would be useful in analysing the regulatory mechanisms in anti-ss-DNA nd anti-ds-DNA antibody production, and application of this kind of therapy in the treatment of systemic lupus erythematosus is suggested.

Aging↗
PubMed1982

Relationship between complement-fixing (hemolytic) antibodies to single-stranded and double-stranded DNA and the prognosis in systemic lupus erythematosus.

Hemolytic (complement-fixing) antibodies to single-stranded (ss) or double-stranded (ds) DNA, measured by recently developed PHL assay, occurred closely correlated with renal activity in patients with systemic lupus (SLE). Approximately one third of the patients with renal disease had hemolytic antibodies to ss-DNA but never to ds-DNA. Hemolytic antibodies were scarcely detectable in patients with mild course. Serial studies also revealed that the estimation of the hemolytic antibodies to ds- and/or ss-DNA was particularly valuable in predicting the future course of the SLE. The emergence of hemolytic antibodies to DNA may be an ominous sign suggestive of grave prognosis in SLE.

Adolescent↗