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)

We have performed an immunohistochemical study of immunoblastic T cell lymphoma and enteropathy-associated T cell lymphoma for alpha-1 anti-trypsin and CD30. Cytoplasmic staining for alpha 1 anti-trypsin is present in the malignant cells in both types of T cell neoplasm which also express CD30, a marker of lymphoid activation. Peripheral blood T lymphocytes on stimulation with mitogen also show granular cytoplasmic expression of alpha 1 anti-trypsin. Time course studies show that this parallels the expression of CD30. Alpha 1 anti-trypsin expression appears therefore to be associated with activation in T cells. Further studies of sub-fractionated T lymphocytes in vitro suggest that the expression of alpha 1 anti-trypsin on activation is not restricted to an individual lymphocyte subset.
 ...
PMID:Alpha-1 anti-trypsin and CD30 expression occur in parallel in activated T cells. 131 6

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.
 ...
PMID:DEL cell line: a "malignant histiocytosis" CD30+ t(5;6)(q35;p21) cell line. 230 42

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.
 ...
PMID:The role of lymphocytes, granulocytes, mast cells and their related cytokines in lesional skin of linear IgA bullous dermatosis. 1035 73

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.
 ...
PMID:Further support for a role for Th2-like cytokines in blister formation of pemphigus. 1116 84

In an attempt to identify novel diagnostic markers for mast cell (MC)-proliferative disorders, serial bone marrow (bm) sections of 22 patients with mastocytosis (systemic indolent mastocytosis, n = 19; mast cell leukemia [MCL], n = 1; isolated bm mastocytosis, n = 2) were analyzed by immunohistochemistry using antibodies against CD2, CD15, CD29, CD30, CD31, CD34, CD45, CD51, CD56, CD68R, CD117, HLA-DR, bcl-2, bcl-x(L), myeloperoxidase (MPO), and tryptase. Staining results revealed expression of bcl-x(L), CD68R, and tryptase in neoplastic MCs (focal dense infiltrates) in all patients. Mastocytosis infiltrates were also immunoreactive for CD45, CD117 (Kit), and HLA-DR. In most cases, the CD2 antibody produced reactivity with bm MCs in mastocytosis, whereas in control cases (reactive bm, immunocytoma, myelodysplastic syndrome), MCs were consistently CD2 negative. Expression of bcl-2 was detectable in a subset of MCs in the patient with MCL, whereas no reactivity was seen in patients with SIM or bm mastocytosis. Mastocytosis infiltrates did not react with antibodies against CD15, CD30, CD31, CD34, or MPO. In summary, our data confirm the diagnostic value of staining for tryptase, Kit, and CD68R in mastocytosis. Apart from these, CD2 may be a novel useful marker because MCs in mastocytosis frequently express this antigen, whereas MCs in other pathologic conditions are CD2 negative.
 ...
PMID:Immunohistochemical properties of bone marrow mast cells in systemic mastocytosis: evidence for expression of CD2, CD117/Kit, and bcl-x(L). 1138 74

Hodgkin's disease (HD) tumours are characterized by the presence of few tumour cells, the Hodgkin and Reed-Sternberg (HRS) cells, surrounded by a large amount of non-neoplastic cells. The role of this cell infiltrate for the development of HD is not known. CD30, belonging to the tumour necrosis factor receptor superfamily, is highly expressed on HRS cells and believed to be involved in tumourigenesis and tumour progression. Tumour samples from 42 patients were immunohistochemically double-stained for tryptase, a mast cell-specific proteinase and CD30 ligand (CD30L). Tryptase-positive mast cells were present in all tumours. Of these cells, 50% expressed CD30L and 66% of the CD30L-positive cells were mast cells. CD30L mRNA in in vitro developed normal mast cells and malignant human and murine mast cell lines was detected using reverse transcription polymerase chain reaction. CD30L protein expressed on human mast cells was detected using flow cytometry. In a co-culture assay, the human mast cell line HMC-1 stimulated thymidine uptake in HRS cell lines, and the stimulation could be blocked using CD30L-specific monoclonal antibodies. In conclusion, mast cells are present in HD tumours and are the predominant CD30L-expressing cells. CD30L-CD30 interaction is a pathway by which mast cells may stimulate DNA synthesis in HRS cells.
 ...
PMID:Mast cells express functional CD30 ligand and are the predominant CD30L-positive cells in Hodgkin's disease. 1155 87

Hodgkin's lymphoma (HL) is characterized by a few Hodgkin, Reed-Sternberg cells (HRS) surrounded by benign cells. We recently reported that mast cells were the predominant CD30L-positive cells in HL tumours, and that they activate HRS in vitro through CD30L-CD30 interaction. Here, we investigated the clinical importance of mast cell infiltration in the tumours of 123 patients. Tumour specimens were stained with a mast-cell-specific antibody that detects tryptase. Mast cells were detected in virtually every case and increasing numbers of mast cells correlated to nodular sclerosis histology (P = 0.008). Patients with higher mast cell infiltration had a worse relapse-free survival (P = 0.01).
 ...
PMID:Mast cell infiltration correlates with poor prognosis in Hodgkin's lymphoma. 1235 14

Human embryonic stem cells (hESCs) are thought to be susceptible to chromosomal rearrangements as a consequence of single cell dissociation. Compared in this study are two methods of dissociation that do not generate single cell suspensions (collagenase and EDTA) with an enzymatic procedure using trypsin combined with the calcium-specific chelator EGTA (TEG), that does generate a single cell suspension, over 10 passages. Cells passaged by single cell dissociation using TEG retained a normal karyotype. However, cells passaged using EDTA, without trypsin, acquired an isochromosome p7 in three replicates of one experiment. In all of the TEG, collagenase and EDTA-treated cultures, cells retained consistent telomere length and potentiality, demonstrating that single cell dissociation can be used to maintain karyotypically and phenotypically normal hESCs. However, competitive genomic hybridization revealed that subkaryotypic deletions and amplifications could accumulate over time, reinforcing that present culture regimes remain suboptimal. In all cultures the cell surface marker CD30, reportedly expressed on embryonal carcinoma but not karyoptically normal ESCs, was expressed on hESCs with both normal and abnormal karyotype, but was upregulated on the latter.
 ...
PMID:Human embryonic stem cells passaged using enzymatic methods retain a normal karyotype and express CD30. 1824 Nov 27

Diagnosis of systemic mastocytosis (SM) is mainly based on the morphological demonstration of compact mast cell infiltrates in various tissue sites. In almost all patients such infiltrates are detected in the bone marrow. Reliable immunohistochemical markers for the diagnosis and grading of SM have been established, but various differential diagnoses including myeloproliferative neoplasms, basophilic and eosinophilic leukemias may be very difficult to delineate. Even more challenging is the recognition of hematological neoplasms with signs of mast cell differentiation but not fulfilling diagnostic criteria for SM, especially the rare myelomastocytic leukemia. It is also important to separate the reactive state of mast cell hyperplasia from indolent variants of SM, especially those with a very low degree of bone marrow infiltration and absence of compact mast cell infiltrates. When the lymphocytic component of the SM infiltrate is very prominent, SM may be confused with an indolent lymphoma, especially lymphoplasmacytic lymphoma which almost always shows a marked reactive increase in mast cells. In aggressive and leukemic variants of SM, mast cells may be very atypical and devoid of metachromatic granules. This hypogranulation can be regarded as cellular atypia and may lead to the misdiagnosis aspect of monocytic leukemia or histiocytic neoplasm. Regarding immunohistochemical anomalies, mast cells in aggressive and leukemic SM have been found to express CD30 (Ki1-antigen). Thus, anaplastic large cell lymphoma or Hodgkin's disease may first be considered rather than SM. There is increasing evidence that most patients with long-standing adult-type urticaria pigmentosa-like skin lesions have in fact indolent SM. Therefore, such skin lesions are an important clue to the correct diagnosis in these patients. However, in aggressive or leukemic SM skin lesions are usually absent and then the correct diagnosis relies on an appropriate investigation of bone marrow biopsy specimens using both SM-related immunohistochemical markers (tryptase, KIT, CD25, CD30) but also markers excluding potential differential diagnoses. Investigation for presence of the activating KIT point mutation D816V is very helpful to establish a correct diagnosis of SM in all the difficult cases exhibiting a low degree of bone marrow infiltration or puzzling morphological findings.
 ...
PMID:Differential diagnoses of systemic mastocytosis in routinely processed bone marrow biopsy specimens: a review. 2061 12

A 21-year-old female presented with a 5-year history of an erythematous papule on her right breast. The biopsy showed a dense, dermal nodular infiltrate, extending focally into the subcutaneous tissue. The infiltrate was composed predominantly of pleomorphic cells with bi-lobed, multi-lobed, horseshoe, or ring-shaped nuclei. There was a smaller subset of monomorphous cells characterized by a round, reniform, or elongated single-lobed nucleus. Accompanying cells included few foamy histiocytes, lymphocytes, and numerous scattered eosinophils. No necrosis, vascular invasion, or ulceration was present. The pleomorphic and monomorphic granular cells were positive for Giemsa stain as well as for tryptase, CD117, CD68, CD2, and CD30 immunohistochemistry and negative for S100, CD1a, myeloperoxidase, lysozyme, and CD56. Clinical examination was negative for any additional similar lesions and serum tryptase was within normal limits. The bone marrow was not biopsied. In addition, fluorescent in situ hybridization revealed multiple clones with loss of number 5 chromosome and PDGFRA and HRAS mutations. The lesion did not recur or progress after a 6-year clinical follow-up. To our full knowledge, we report the first case of pleomorphic mastocytoma with loss of chromosome 5 and PDGFRA and HRAS mutations.
 ...
PMID:Pleomorphic mastocytoma associated with loss of chromosome 5, PDGFRA, and HRAS mutations: A case of cutaneous mastocytosis with severe atypia and indolent behavior. 3289 8


1