Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this paper an immunodominant epitope of Topoisomerase I is described. An epitope expression sublibrary was constructed from Topoisomerase I cDNA. The subclones were screened with an antiserum from a patient with systemic sclerosis (SSc). The positive clones defined one immunodominant B cell epitope (epitope III), which was located at the carboxyterminal part of the protein. The epitope, 52 amino acids in length, neither contains the p30gag sequence nor the suggested active site Tyr-723, both presumed antibody recognition sites. More than 70% of our anti-TopoI sera recognize this epitope III, indicating that it is a major recognition site of the anti-TopoI autoantibodies in SSc sera. DNA relaxation experiments show that all sera that recognize epitope III and most sera with antibodies to other epitopes inhibit Topoisomerase I activity.
Mol Biol Rep 1992 May
PMID:Analysis of an immunodominant epitope of topoisomerase I in patients with systemic sclerosis. 131 98

The tight-skin (Tsk) mouse is a genetic model of pulmonary emphysema linked to a deficiency of serum antielastase. In this mouse occurrence of connective tissue abnormalities in various organs (systemic scleroderma) has been reported. The aim of the present work was to study lung collagen synthesis and deposition in Tsk mice. No differences in the collagen synthesis rate and morphology at the ultrastructural level were found in Tsk mice at birth. At 2 months of age, a marked increase in collagen was observed within the alveolar septa. At this time, an increased lung collagen synthesis, assessed by determining prolyl hydroxylase activity and incorporation of radiolabeled proline, was found in Tsk mice with respect to control mice. However, due to the ongoing parenchymal destruction, the values of total lung collagen at 6 and 12 months of age were only moderately but significantly increased with respect to those observed at 2 months. As a consequence, a progressive accumulation of lung collagen fibers was observed in the residual septa. The increase in collagen deposition was accompanied by a relative increase in type I collagen. Although the data in the literature would suggest a genetic cause for the lung collagen change in Tsk mice, the data presented here indicate that the change in lung collagen metabolism may be a part of a remodeling process taking place after lung destruction.
Exp Mol Pathol 1992 Apr
PMID:Lung collagen synthesis and deposition in tight-skin mice with genetic emphysema. 158 42

Protein patterns of Japanese newt papilloma in vivo at low (4 degrees C), normal (10 degrees C, control) and elevated (30 degrees C) temperature were investigated by two-dimensional gel electrophoresis. There were nine protein spots in normal skin (skin specific spots: SSS) which did not exist in papillomas. At 10 degrees C, the papillomas possessed three specific protein spots (papilloma specific spots: PSS) which did not appear in normal skin. At the reduced environmental temperature, eight of the nine missing proteins in papillomas had reappeared by 12 weeks exposure. Differential responses in reappearance of SSS in papillomas varied with environmental temperature. The PSS generally were unchanged by environmental temperature modulation, although one specific protein disappeared at 12 weeks at 4 degrees C. Reappearance of normal SSS in papillomas occurred early in treatment and reflected only minor variations in high versus low temperature exposures. These data suggest that temperature-induced tumor regression may be associated with changes in protein composition.
Cell Mol Biol 1989
PMID:Temperature-induced alterations in protein composition of newt papilloma cells. 262 5

Eleven axillary lymph nodes from patients with different cutaneous disorders (systemic scleroderma, atopic eczema, psoriasis, hairy cell erythroderma, dermatopathic lymphadenitis) were examined by electron microscopy. In systemic scleroderma interdigitating cells (IDC's) showed typical ultrastructural features as well as intimate contacts with neighboring lymphocytes. In atopic eczema IDC's were characterized by widespread invaginations of the cell membrane, and an increase in tubulo-vesicular structures and microfilaments. Similar observations have been made in dermatopathic lymphadenitis. In psoriasis and hairy cell erythroderma. IDC's showed only a few interdigitations and invaginations of the cell surface. It is supposed that these structural changes in IDC's reflect the different immunological conditions of the diverse cutaneous disorders.
Virchows Arch B Cell Pathol Incl Mol Pathol 1980
PMID:Ultrastructural differences of interdigitating cells in human lymph nodes. 610 48

In addition to its procoagulant properties, the serine protease thrombin increases endothelial permeability, stimulates granulocyte adherence, and serves as a fibroblast mitogen. We demonstrate that thrombin is mitogenic for human lung fibroblasts in vitro. The mitogenic effect of thrombin is associated with an increase in the expression of the ligand PDGF-AA and up-regulation of PDGF alpha-receptor. Since scleroderma (systemic sclerosis; SSc) is characterized by widespread microvascular injury and is frequently complicated by pulmonary fibrosis, we sought to determine the level of thrombin activity in bronchoalveolar lavage (BAL) fluid from SSc patients and normal controls. We report a significantly higher level of thrombin activity in BAL fluid from SSc patients compared with normal controls (P < 0.001). Taken together, the high levels of thrombin in BAL fluid and its demonstrated mitogenicity for lung fibroblasts suggest an important role for thrombin in the pathogenesis of SSc and perhaps other fibrotic lung diseases.
Am J Respir Cell Mol Biol 1994 Apr
PMID:Scleroderma bronchoalveolar lavage fluid contains thrombin, a mediator of human lung fibroblast proliferation via induction of platelet-derived growth factor alpha-receptor. 751 Sep 86

In the previous studies we have shown that tight-skin (TSK) mouse is an experimental model for systemic sclerosis. This mutant mouse develops autoantibodies specific for scleroderma target antigens. To determine whether the expansion of autoantibody repertoire in TSK mouse occurs by selective expansion of certain variable region gene families, and whether CD5+ B cells contribute significantly to the production of autoantibodies, we have analyzed a panel of 60 hybridomas producing autoantibodies specific for scleroderma target autoantigens. Northern analysis of RNAs from these hybridomas showed that 70% were expressing genes from VHJ558 family while genes from 36-09 and J606 families were not at all represented. In contrast, in the cDNA libraries derived from splenic B cells, the expression of VHJ558 and 36-09 gene families were at an expected frequency corresponding to their genomic complexity (44% and 11.6%, respectively). These results demonstrate that there is a strong bias toward the use of J558 genes in TSK mouse autoantibody repertoire. On the other hand the expression of VK gene families was mostly random and corresponded to their frequency in splenic C kappa cDNA library. The pairing of VH:VK genes was stochastic. Analysis of the expression of J segments, however, revealed that JH2 and JK2 were predominantly used in the autoantibodies. Analysis of the expression CD5 mRNA in these hybridomas indicate that CD5+ B cells do not contribute significantly to the autoimmunity in TSK mice. These findings suggest that the expansion of peripheral autoreactive B cells in TSK mouse is determined by their immunoglobulin variable region rather than the genetic properties linked to a particular B cell subset.
Mol Immunol 1993 Aug
PMID:Tight-skin mouse autoantibody repertoire: analysis of VH and VK gene usage. 768 52

Pulmonary fibrosis is a major cause of morbidity and mortality in patients with systemic sclerosis (SSc). The pathogenesis of this condition is poorly understood, but one of the earliest pathologic features is endothelial and epithelial cell injury with subsequent regeneration. Endothelial and epithelial cells can release several mediators, including endothelin-1 (ET-1). In this study, we investigated the levels of ET-1 in bronchoalveolar lavage fluid (BALF) from patients with SSc and assessed the contribution of ET-1 to the fibroblast mitogenic activity induced by these fluids. A total of 26 patients were evaluated and divided into those with evidence of pulmonary fibrosis, assessed by thin-section computed tomography (group I, n = 16), and those with a normal scan (group II, n = 10). BALF from both groups of patients stimulated fibroblast proliferation. Values expressed as median (range) percentage increase above media controls were 25.5% (5.0 to 47.8%) and 27.6% (10.9 to 51.6%) for groups I and II, respectively (P < 0.02 in both cases). Mitogenic activity was inhibited by about 40% in the presence of either a neutralizing antibody to ET-1 or two synthetic ET-1 receptor ligands. Levels of ET-1 in BALF, expressed as medians (range) were 2.90 ng/mg albumin (0.68 to 5.75) in patients with SSc and 1.23 ng/mg albumin (0.84 to 2.0) in control patients (P < 0.02). Furthermore, ET-1 levels in BALF from patients in group II (3.83 ng/mg albumin, range 1.76 to 5.75) were elevated compared with those in group I (2.62 ng/mg albumin, range 0.68 to 3.81; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1994 Oct
PMID:Increased levels of endothelin-1 in bronchoalveolar lavage fluid from patients with systemic sclerosis contribute to fibroblast mitogenic activity in vitro. 791 11

Anti-nucleolin antibodies have been detected in patients with systemic connective tissue diseases (SCTD) including systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). In vivo bound autoantibodies to nucleoli of epidermal keratinocytes have been demonstrated in skin from patients with SCTD. In this study, monoclonal antibody to nucleolin (D-3) was used to determine the distribution of nucleolin in different culture cells including HEp-2, HepG2, HRCC, Molt-4 and Wil2 cells. Nucleolin was found to be present on the surface of HEp-2 and HepG2 cells, but not on the surface of HRCC and lymphoblastoid (Molt-4 and Wil2) cells; in contrast, nucleolin was detected in the nucleoli of all permeabilized cells examined. In immunoprecipitation, using extracts from 32P-labeled HEp-2 cells as antigenic source, cell membrane as well as nuclear nucleolins were found to be phosphorylated with a molecular weight of 105 kDa. Viable HEp-2 and HepG2 cells were cocultured with IgG fraction of D-3 in a CO2 incubator for 1 to 24 h, and then permeabilized with acetone followed by immunofluorescence staining with FITC-labeled goat anti-mouse IgG antibodies. Nucleolar staining was observed in cells after 10 h or longer of coculture. These data indicated that D-3 antibody reacted with cell membrane nucleolin and subsequently gain access into cells in a process related to pinocytosis.
Mol Biol Rep 1996
PMID:Internalization of anti-nucleolin antibody into viable HEp-2 cells. 911 28

Computer retrieval in a database, comprising 7,225 muscle cases, revealed that mitochondrial myopathies do not occur more frequently in inflammatory myopathies (3.74%) than in the whole series (3.69%). A more detailed study of inclusion body myositis (IBM), however, showed that severe mitochondrial alterations were apparent in about twice as many IBM cases as expected. This confirms recent studies of others although a causal relationship has thus far not been established. Identification of mitochondrial deletions by Southern blotting corresponded to the presence of severe structural abnormalities of mitochondria. Peripheral neuropathy of variable severity was noted in all cases of IBM and mitochondrial myopathy. By contrast, the association of severe mitochondrial abnormalities with polymyositis, systemic scleroderma, and vasculitis observed in some cases of the present series may be incidental or age dependent.
Mol Cell Biochem 1997 Sep
PMID:Mitochondrial abnormalities and peripheral neuropathy in inflammatory myopathy, especially inclusion body myositis. 930

Human interleukin 13 (IL-13) is a cytokine that has a profound effect on primary immune cells by inducing immunoglobulin production, proliferation of B cells, and the differentiation of cells of the monocytic lineage. IL-13 can inhibit the production of inflammatory cytokines by both macrophages and monocytes. Previously, IL-13 expression has been reported only in cells of the T-cell lineage and the mast cell line HMC-1. We now report the presence of IL-13 mRNA and protein in human alveolar macrophages (AMs) analyzed by the reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunoabsorbent assay (ELISA), respectively, and IL-13 protein in bronchoalveolar lavage fluid (BALF) of subjects with pulmonary fibrosis. We have investigated 13 patients from 49 to 75 yr of age with forms of pulmonary fibrosis, and eight healthy volunteers from 24 to 61 yr of age. Their AMs were obtained by bronchoalveolar lavage (BAL) and purified by adherence. The proportion of BAL purified AMs expressing IL-13 mRNA was increased in those subjects with fibrotic lung disease, in comparison with those from control subjects (11 of 13 versus 2 of 8, P < 0.01). IL-13 protein was detectable in the BALF of 8 of 13 patients with pulmonary fibrosis, but in none of the control subjects. AMs of four subjects with systemic sclerosis were cultured and IL-13 protein was increased in the culture supernatants when compared to the control subjects, although this did not reach significance. These findings show that IL-13 mRNA is not only a product of T cells, but is also expressed in both normal AMs and those from subjects with pulmonary fibrosis, and that at least some of the IL-13 mRNA is translated into protein and secreted in subjects with pulmonary fibrosis. We hypothesize that IL-13 may be expressed by normal human AMs as part of the homeostatic control process but its production may be increased in the presence of inflammatory lung disease.
Am J Respir Cell Mol Biol 1998 Jan
PMID:Production of interleukin 13 by alveolar macrophages from normal and fibrotic lung. 944 46


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