Tuberculide of the penis without ulceration.
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Biomedical subjects
Publications and source records attributed to T Kadono.
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Nuclear palisading is a characteristic feature which is typically seen in neural tumours such as neurilemmoma, and also in some other tumours. We report here three patients with basal cell carcinoma who showed histological patterns similar to nuclear palisading. To our knowledge, this is the first such case report in the medical literature; we apply the term 'neuroid-type nuclear palisading' to these cases. In our patients, the spindle-shaped tumour cells were tightly packed and the nuclei were arranged uniformly to form this rare feature.
Vascular endothelial growth factor (VEGF) is an angiogenic cytokine which has been reported to be important in the pathogenesis of rheumatoid arthritis (RA). In this study, the serum level of VEGF was measured using enzyme-linked immunosorbent assay in 17 patients with systemic lupus erythematosus, 49 patients with polymyositis/dermatomyositis (PM/DM), 40 patients with systemic lupus erythematosus, 49 patients with polymyositis/dermatomyositis (PM/DM), 40 patients with systemic sclerosis (SSc), 11 patients with RA and 20 control subjects. The VEGF level was 184 +/- 62 pg/mL (mean +/- SD) in the serum of normal individuals. The mean VEGF levels in the patients with PM/DM or RA were significantly higher than in the normal controls. In 21 of the 49 patients with PM/DM and nine of the 11 patients with RA, the serum VEGF level was considered to be elevated. In patients with SSc, those with diffuse cutaneous SSc showed elevated VEGF levels in comparison with normal controls. An elevated serum VEGF level was correlated with the frequency of lung fibrosis and reduced vital capacity in the patients with SSc.
OBJECTIVE: To determine additional abnormal characteristics related to cytokines in fibroblasts derived from systemic sclerosis (SSc), we examined the production of interleukin 6 (IL-6) and IL-8 and their mRNA levels both in scleroderma fibroblasts and in those from normal skin. METHODS: Cultured fibroblasts from patients with SSc and healthy controls were examined. Production of IL-6 and IL-8 was assessed by specific ELISA, and the levels of IL-6 and IL-8 mRNA were determined by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Basal production of both IL-6 and IL-8 was significantly increased in scleroderma fibroblasts compared with controls. When cells were stimulated with either IL-1beta (50 pg/ml) or tumor necrosis factor-alpha (TNF-alpha: 10 ng/ml), the production of IL-6 and IL-8 was predominantly increased in both cell strains and there was no significant difference in the production of IL-6 and IL-8 between them. When normal fibroblasts were stimulated with IL-1beta for 48 h and subcultured, both IL-6 and IL-8 production were significantly increased, and production remained elevated even after 3 passages. RT-PCR revealed that IL-6 and IL-8 mRNA were detected in scleroderma fibroblasts but not in normal skin fibroblasts without cytokine stimulation. When stimulated with IL-1beta, both cell strains expressed IL-6 and IL-8 mRNA to almost the same extent. CONCLUSION: Increased production of IL-6 and IL-8 by scleroderma fibroblasts suggests that these cells may have been stimulated by certain cytokines in vivo.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.