Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Yam 1B, a human B lymphoblastoid cell line, spontaneously produced an immunoregulatory factor, which suppresses blastogenesis and antibody formation by human lymphocytes. The Yam 1B cells, which were derived from the peripheral blood of an adult T-cell leukemia patient, have been established and maintained in our laboratory since 1985. This cell line expressed mature B-cell surface antigens including surface immunoglobulin M (IgM), CD23, and HLA-DR; had cytoplasmic IgM; and secreted small amounts of IgM in the culture supernatants. Yam 1B was positive for Epstein-Barr virus-associated antigen (EBNA) but negative for adult T-cell-associated antigen (ATLA). The serum-free Yam 1B culture supernatants (SN) inhibited the expression of transferrin R, but neither the expression of interleukin 2 (IL-2) R(CD25) nor the production of IL-2 in the lymphocytes stimulated with phytohemagglutin. Yam 1B SN also inhibited DNA synthesis by human T and B lymphocytes and immunoglobulin generation by normal B cells as well as by Epstein-Barr virus-transformed human B lymphoblastoid cell lines. The inhibitory activity of Yam 1B SN was inactivated at 56 degrees C and at pH 10 but was relatively stable at pH 2. It was abrogated by digestion with pronase and was partially stable by digestion with trypsin. Fractions collected from a Sephacryl S-300 gel filtration column (Pharmacia Fine Chemicals, Uppsala, Sweden) were found to have a peak of inhibitory activity of cell proliferation associated with molecules of apparent MWr of 43,000 to 67,000. The inhibitory activity of Yam 1B SN was not blocked by the anti-transforming growth factor beta antibody.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of lymphocyte blastogenesis and antibody production by soluble factor released by a human B-lymphoblastoid cell line. 179 Mar 7

A new cell line DEL, established in vitro, was isolated from a pleural effusion of a boy who died of malignant histiocytosis. Its principal characteristics are: strong positivity with monoclonal antibodies (MAbs) to CD25, CD30, CD45R, KiM7, EMA, HLA Cl I and II; constant presence of acid phosphatase, ANAE, alpha-anti-trypsin, alpha-anti-chymotrypsin and NBT reductase activity; rearrangement of the immunoglobulin heavy-chain gene (JH) and a germ-line configuration of the T-chain gene; and finally a translocation between chromosomes 5-6 with a breakpoint in 5q35. The DEL cell line is appropriate for studying the role of the 5q localized c-fms oncogene and of the genes of the mononuclear phagocyte growth factor (CSFI) and of their receptors in the dynamics and etiology of malignant hemopathies associated with a 5q35 breakpoint.
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PMID:DEL cell line: a "malignant histiocytosis" CD30+ t(5;6)(q35;p21) cell line. 230 42

Immunosuppression observed in patients with malignancy may be due to factors released by tumour cells. Medium conditioned by COLO 205 cells was found to inhibit mitogen-stimulated lymphocyte proliferation. Examination of CD25 and Class II MHC induction on PBMC incubated in complete, or COLO 205 conditioned, medium was not significant. The prevalence of lymphocytes in the S-phase of the cell cycle was enhanced after mitogenic stimulation and addition of COLO 205 conditioned medium. This was balanced by a concomitant fall in proportion of cells in the G0/G1 phases of the cell cycle. The immunosuppressive properties of COLO 205 conditioned medium was abrogated by heating to 60 degrees C for 30 min and by digestion with trypsin. Fractionation of the medium by gel filtration yielded two immunosuppressive fractions with relative molecular weights of 60,000 and below 20,000. It was concluded that cultured COLO 205 cells produce immunosuppressive protein/peptide factors which block cell proliferation during DNA synthesis. These factors fail to prevent upregulation of membrane-associated markers of cell activation.
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PMID:Production of immunosuppressive factors by a cultured tumour cell line and their effect on lymphocyte proliferation and cell cycle response. 825 15

Although Type I allergy is a trigger for provoking chronic inflammation, whether allergic sinusitis (AS) can be distinguished from sinusitis due to chronic infection is still debated. This study was performed to characterize inflammatory cells in AS and to determine whether patients with AS differ from patients with chronic suppurative sinusitis (CSS). 5 patients with AS and 10 patients with CSS were investigated. Cellular infiltration was studied using immunohistochemistry with monoclonal antibodies using CD3, CD4, CD8, CD25, major basic protein (BMK13), eosinophil cationic protein (EG2), neutrophil elastase, and tryptase. There were no differences in CD3+, CD4+, CD25+, and tryptase+ cells between the groups. Whereas the total number of eosinophils (BMK13+) also did not significantly differ, the number of activated eosinophils (EG2+) was significantly higher (P < 0.05) in patients with AS. Furthermore, a statistically significant increase in the percentage of activated eosinophils to total eosinophils (P < 0.05) was observed in patients with AS. In contrast, the number of neutrophil elastase+ cells was significantly higher (P < 0.05) in patients with CSS. These results suggest that patients with AS can be distinguished immunohistochemically from patients with CSS, with AS being distinguished by activated eosinophil infiltration.
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PMID:Preferential infiltration by activated eosinophils in allergic sinusitis. 925 57

Ketotifen is marketed throughout the world as an antiallergy drug, but whether it affects infiltration of inflammatory cells into airway mucosa is not known. We studied the effects of ketotifen on symptoms, pulmonary function, and airway inflammation in 25 patients with atopic asthma. Patients took ketotifen (1 mg twice daily) or a matching placebo for 8 weeks in a double-blind, parallel-group study. Data recorded on diary cards were used for 2 weeks before treatment began, and they were used for the last 2 weeks of treatment to study asthma symptoms, use of beta 2-agonists, and peak expiratory flow (PEF). Pulmonary function tests, bronchial responsiveness to methacholine, and fiberoptic bronchoscopy were performed before and after treatment. Biopsy specimens were obtained by bronchoscopy. Specimens were stained immunohistochemically with monoclonal antibodies against stored eosinophil cationic protein (EG1), the secreted form of eosinophil cationic protein (EG2), mast-cell tryptase (AA1), neutrophil elastase (NP57), CD3, CD4, CD8, and CD25. The numbers of positively stained cells in the lamina propria were counted. Compared with the placebo, the ketotifen-treated group exhibited significant improvement of asthma symptoms (P < 0.05) and bronchial responsiveness (P < 0.05). This was accompanied by a reduction of EG2+ eosinophils (P < 0.05), CD3+ T cells (P < 0.001), CD4+ T cells (P < 0.01), and CD25+ activated T cells (P < 0.01) in the bronchial mucosa. These results suggested that the beneficial effects of ketotifen in bronchial asthma may result from consequent inhibition of activated eosinophils and T-cell recruitment into the airway. Moreover, ketotifen may relieve allergic inflammation in bronchial asthma.
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PMID:Effects of ketotifen on symptoms and on bronchial mucosa in patients with atopic asthma. 928 80

Asthma at night is characterized by a nocturnal increase in airway obstruction. It has been hypothesized that nocturnal asthma results from an increase in airway wall inflammation at night. However, studies on inflammatory cells in bronchoalveolar lavage (BAL) fluid and bronchial biopsies have produced conflicting data. This study assessed inflammatory cell numbers at 16:00 h and 04:00 h in bronchial biopsies of 13 healthy controls, 15 asthmatic patients with peak expiratory flow (PEF) variation < or =15% and 10 asthmatic patients with PEF variation >15%. There was no significant increase at night in the number of CD3, CD4, CD8, CD25, AAI (tryptase) and EG2-immunopositive cells in the submucosa in both groups. Numbers of EG2-positive cells in the two asthmatic groups were significantly higher than in healthy controls, both at 16:00 h (p<0.05) and 04:00 h (p<0.01). The number of EG2, CD4 and CD25-positive cells at 04:00 and 16:00 h tended to be higher in asthmatics with a PEF variation >15% than in asthmatics with PEF variation < or =15%. At 04:00 h the median numbers of EG2-positive cells (per mm basement membrane) in subjects with PEF variation >15% and < or =15% were 6 and 3 cells, respectively, and at 16:00 h 4 and 25 cells respectively. Increased nocturnal airway obstruction is not associated with increased numbers of inflammatory cells in the bronchial submucosa at night. Apparently, asthmatic patients with a peak expiratory flow variation >15% suffer from a higher overall severity of bronchial inflammation at night and during the day.
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PMID:Increased peak expiratory flow variation in asthma: severe persistent increase but not nocturnal worsening of airway inflammation. 976 77

Linear IgA bullous dermatosis (LAD) is an acquired, heterogeneous, subepidermal blistering disease characterized by linear IgA deposits at the dermoepidermal basement membrane zone (BMZ), often with circulating IgA antibodies to the BMZ. The pathogenetic mechanism, possibly related to the immunophenotype of infiltrating cells, as well as the potential role of cytokines in determining bullous lesions, have not yet been elucidated. An immunohistochemical study was performed with a large panel of monoclonal antibodies [to CD3, CD4, CD8, CD25, CD1a, CD30, CD54, CD50, endothelial leucocyte adhesion molecule-1, vascular cell adhesion molecule-1, myeloperoxidase (MPO), eosinophil cationic protein EG1 and EG2, tryptase, HLA-DR, human interleukin (IL)-3, human IL-5, human IL-8, human IL-4, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and granulocyte/macrophage colony-stimulating factor] using the alkaline phosphatase-antialkaline phosphatase procedure on lesional and perilesional skin of nine patients (one male, eight female; age range 8 months-80 years) with clinical, histological and immunofluorescent proven LAD. The predominant infiltrating cells, distributed mostly inside and below the bullae, were neutrophils and eosinophils which showed intense activation (MPO +, EG1 +, EG2 +). The lymphocytic infiltrate, consisting principally of CD4 +, HLA-DR + and CD30 + T cells, had a predominantly perivascular distribution. Proinflammatory cytokines, such as TNF-alpha and IFN-gamma, showed a moderate focal expression on the dermal perivascular sites; IL-8 was found to have a particularly intense staining on all the epidermal cell layers and at perivascular and vascular sites. Other cytokines, such as IL-4 and IL-5, showed a prevalent intracytoplasmic staining on some cells of the dermal infiltrate (probably mastocytes and lymphocytes), and at the dermal-epidermal separation sites there was also an intense scattered distribution of IL-5. The specific tissue lesions of LAD may be the consequence of the IgA deposits at the BMZ and also of the release of these cytokines together with tissue damage enzymes derived from neutrophils or eosinophils.
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PMID:The role of lymphocytes, granulocytes, mast cells and their related cytokines in lesional skin of linear IgA bullous dermatosis. 1035 73

One of the major advances in the histological diagnosis of bone marrow (BM) involvement in mastocytosis has been the specific immunohistochemical detection of tryptase on most cells (MC), which has shown to be of great diagnostic value, especially in cases of malignant mastocytosis. On the other hand, recent studies have clearly shown that bone marrow mast cells can be specifically identified and accurately enumerated using multiparametric flow cytometry, which allow a systematic analysis of the immunophenotypic characteristics of bone marrow mast cells. Once this flow cytometric approach was applied for the analysis of BMMC from mastocytosis patients clear immunophenotypical differences were found between BMMC from normal individuals and adults with mastocytosis. The most characteristic immunophenotypic feature, both in malignant and adult indolent systemic mast cell disease, being the coexpression of CD2 and CD25 antigens, never present in normal bone marrow mast cells and, which constitute an aberrant hallmark of bone marrow mast cells in adult mastocytosis. Furthermore, bone mast cells from mastocytosis display a higher reactivity for CD35, CD63, and CD69 activation-associated antigens. Based on these results it could be concluded that the use of multiparametric flow cytometric immunophenotyping of BMMC in adult patients suffering from cutaneous mastocytosis can be of great utility for the diagnosis of BM involvement; additionally, this might also help to establish the real incidence of BM involvement in cutaneous mastocytosis.
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PMID:Immunophenotype of bone marrow mast cells in indolent systemic mast cell disease in adults. 1070 45

Pemphigus vulgaris and pemphigus foliaceus are commonly known as antibody-mediated bullous diseases. However, recently a role for infiltrating cells as contributors to the pathogenesis of these diseases has been suggested. The aims of our study were to characterize the immunophenotype of the cellular infiltrate of pemphigus lesional skin and to study the cytokines secreted. We have therefore performed an immunohistochemical study with a large panel of monoclonal antibodies (to CD3, CD4, CD8, CD25, CD30, myeloperoxidase, eosinophil cationic protein EG2, tryptase, human interleukin (IL)-2, human IL-4, human IL-5, human IL-6, human IL-8, and interferon (IFN)-gamma using the alkaline phosphatase-antialkaline phosphatase procedure on lesional and uninvolved skin of six patients with clinical, histological, and immunofluorescent proven pemphigus. We also performed RT-PCR in order to demonstrate mRNA expression of the cytokines of interest. Our results suggest the presence of a T cell population with a prevalent Th2-like cytokine pattern in lesional skin. In addition, we demonstrate a consistent number of granulocytes and mast cells that show clear signs of activation. These data suggest the involvement of an inflammatory infiltrate in the production of pemphigus lesions. In particular, we assume that Th2 cells may be implicated in the very early stages of autoimmune response, concluding that they exert broad activity in blister formation.
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PMID:Further support for a role for Th2-like cytokines in blister formation of pemphigus. 1116 84

The diagnosis of bone marrow (BM) involvement in mastocytosis has mainly been based on conventional histology. Nevertheless, in recent years, three major methodological advances have been made: the measurement of serum tryptase levels, the immunohistochemical assessment of mast cell (MC) tryptase, and the immunophenotypical characterization of BMMC using flow cytometry (FCM). The most characteristic immunophenotypic feature in mastocytosis is the coexpression of CD2 and CD25 antigens, which are never present in normal BMMC and constitute a phenotypic hallmark of BMMC in adult mastocytosis. Such observations would support the need to include the immunophenotypic analysis of MC in the diagnosis of mastocytosis.
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PMID:Utility of flow cytometric analysis of mast cells in the diagnosis and classification of adult mastocytosis. 1137 81


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