Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A critical role for complement in the regulation of self tolerance has been proposed to explain the strong association between complement deficiency and autoimmunity. To elucidate the role of the classical pathway of complement in the maintenance of B cell tolerance, C1q-deficient (C1qa-/-) mice were bred with anti-hen egg lysozyme (HEL) immunoglobulin (Ig(HEL)) and soluble HEL (sHEL) transgenic mice. B cell tolerance was intact in C1qa-/- mice. In vivo, double-transgenic (Ig(HEL)/sHEL) C1qa-/- and wild-type control mice down-regulated surface immunoglobulin expression on splenocytes and equivalent numbers of HEL-binding B cells accumulated in the periphery. Maturation of B cells, evidenced by CD21 expression, was retarded to the same extent and at a similar time point. The frequency of anti-HEL-producing plasma cells and serum levels of anti-HEL immunoglobulin were comparably reduced in control and C1qa-/- double-transgenic mice compared to control Ig(HEL) and C1qa-/- Ig(HEL) mice. Furthermore, splenocytes from double-transgenic C1qa-/- or wild-type mice did not modulate intracellular calcium levels after stimulation with HEL in vitro. These data demonstrate that a stable form of B cell anergy persists in the periphery of C1qa-/- mice, suggesting that activation of the classical pathway by C1q is not essential for the maintenance of B cell tolerance in this transgenic model.
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PMID:Intact B cell tolerance in the absence of the first component of the classical complement pathway. 1144 62

True histiocytic lymphoma, as defined by strict criteria, is a very rare neoplasm. We describe three cases occurring as primary tumors in the central nervous system. The patients, two females and one male, ranged in age from 11 to 69 years. The tumors involved the brain in two cases and spinal cord in one, with a size ranging from 7 to 17 mm. Two patients died at 4 months and 8 months, respectively, and one was alive with disease at 5 months. Pathologically, the tumors comprised groups and sheets of noncohesive large cells with pleomorphic vesicular nuclei, distinct nucleoli, and abundant eosinophilic cytoplasm. A dense inflammatory infiltrate consisting of neutrophils, lymphocytes, plasma cells, and histiocytes was present, with multiple foci of necrosis and abscess formation. All three cases demonstrated an identical immunophenotype: positive for CD68 and lysozyme; focally positive for S-100 protein, CD45RB, and CD4; and negative for CD3, CD20, CD21/CD35, CD1a, CD30, ALK1, myeloperoxidase, glial fibrillary acidic protein, and cytokeratin. The proliferative index ranged from 20% to 35%. Ultrastructural examination further confirmed the histiocytic nature of the tumor cells, characterized by irregularly folded or multisegmented nuclei and abundant cytoplasm containing lysosomes; Birbeck granules, interdigitating cell processes, and cell junctions were not found. Although the presence of abundant inflammatory cells could obscure the neoplastic histiocytes, making the distinction from inflammatory conditions difficult, awareness of this unusual histologic feature and the invariable finding of pleomorphic cells in some areas of the lesion permit the correct diagnosis to be made.
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PMID:Primary histiocytic lymphoma of the central nervous system: a neoplasm frequently overshadowed by a prominent inflammatory component. 1168 53

Neoplasms of histiocytes and dendritic cells are rare, and their phenotypic and biological definition is incomplete. Seeking to identify antigens detectable in paraffin-embedded sections that might allow a more complete, rational immunophenotypic classification of histiocytic/dendritic cell neoplasms, the International Lymphoma Study Group (ILSG) stained 61 tumours of suspected histiocytic/dendritic cell type with a panel of 15 antibodies including those reactive with histiocytes (CD68, lysozyme (LYS)), Langerhans cells (CD1a), follicular dendritic cells (FDC: CD21, CD35) and S100 protein. This analysis revealed that 57 cases (93%) fit into four major immunophenotypic groups (one histiocytic and three dendritic cell types) utilizing six markers: CD68, LYS, CD1a, S100, CD21, and CD35. The four (7%) unclassified cases were further classifiable into the above four groups using additional morphological and ultrastructural features. The four groups then included: (i) histiocytic sarcoma (n=18) with the following phenotype: CD68 (100%), LYS (94%), CD1a (0%), S100 (33%), CD21/35 (0%). The median age was 46 years. Presentation was predominantly extranodal (72%) with high mortality (58% dead of disease (DOD)). Three had systemic involvement consistent with 'malignant histiocytosis'; (ii) Langerhans cell tumour (LCT) (n=26) which expressed: CD68 (96%), LYS (42%), CD1a (100%), S100 (100%), CD21/35 (0%). There were two morphological variants: cytologically typical (n=17) designated LCT; and cytologically malignant (n=9) designated Langerhans cell sarcoma (LCS). The LCS were often not easily recognized morphologically as LC-derived, but were diagnosed based on CD1a staining. LCT and LCS differed in median age (33 versus 41 years), male:female ratio (3.7:1 versus 1:2), and death rate (31% versus 50% DOD). Four LCT patients had systemic involvement typical of Letterer-Siwe disease; (iii) follicular dendritic cell tumour/sarcoma (FDCT) (n=13) which expressed: CD68 (54%), LYS (8%), CD1a (0%), S100 (16%), FDC markers CD21/35 (100%), EMA (40%). These patients were adults (median age 65 years) with predominantly localized nodal disease (75%) and low mortality (9% DOD); (iv) interdigitating dendritic cell tumour/sarcoma (IDCT) (n=4) which expressed: CD68 (50%), LYS (25%), CD1a (0%), S100 (100%), CD21/35 (0%). The patients were adults (median 71 years) with localized nodal disease (75%) without mortality (0% DOD). In conclusion, definitive immunophenotypic classification of histiocytic and accessory cell neoplasms into four categories was possible in 93% of the cases using six antigens detected in paraffin-embedded sections. Exceptional cases (7%) were resolvable when added morphological and ultrastructural features were considered. We propose a classification combining immunophenotype and morphology with five categories, including Langerhans cell sarcoma. This simplified scheme is practical for everyday diagnostic use and should provide a framework for additional investigation of these unusual neoplasms.
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PMID:Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. 1212 Dec 33

Pneumolysin is an important virulence factor of Streptococcus pneumoniae, interacting with the membranes of host cells to elicit a multitude of inflammatory responses. We used cDNA microarrays to identify genes which are responsive to S. pneumoniae in a pneumolysin-dependent and -independent fashion. The THP-1 human monocytic cell line was coincubated for 3 h with medium alone, with the virulent type 2 S. pneumoniae strain D39, or with the isogenic strain PLN, which does not express pneumolysin. RNA was isolated from the monocytes and hybridized on cDNA microarrays. Of 4,133 genes evaluated, 142 were found to be responsive in a pneumolysin-dependent fashion, whereas 40 were found to be responsive independent of pneumolysin. Genes that were up-regulated in cells exposed to D39 relative to those exposed to PLN included genes encoding proteins such as mannose binding lectin 1, lysozyme, alpha-1 catenin, cadherin 17, caspases 4 and 6, macrophage inflammatory protein 1beta (MIP-1beta), interleukin 8 (IL-8), monocyte chemotactic protein 3 (MCP-3), IL-2 receptor beta (IL-2Rbeta), IL-15 receptor alpha (IL-15Ralpha), interferon receptor 2, and prostaglandin E synthase. Down-regulated genes included those encoding complement component receptor 2/CD21, platelet-activating factor acetylhydrolase, and oxidized low-density lipoprotein receptor 1 (OLR1). Pneumolysin-independent responses included down-regulation of the genes encoding CD68, CD53, CD24, transforming growth factor beta2, and signal transducers and activators of transcription 1. These results demonstrate the striking effects of pneumolysin on the host cell upon exposure to S. pneumoniae.
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PMID:Pneumolysin-dependent and -independent gene expression identified by cDNA microarray analysis of THP-1 human mononuclear cells stimulated by Streptococcus pneumoniae. 1265 30

Histiocytic sarcoma is a rare malignant neoplasm that occurs in lymph nodes, skin, and the gastrointestinal tract. Many previously published cases were likely misdiagnosed examples of non-Hodgkin lymphoma. Only small numbers of bona fide examples exist in the world literature; cases arising primarily at extranodal sites are not well described and often seem to go unrecognized. To characterize these tumors further, 14 extranodal histiocytic sarcomas were analyzed. Hematoxylin and eosin sections were reexamined, immunohistochemistry was performed, and clinical details were obtained from referring hospitals. Eight patients were female and 6 male (median age, 55 years; range, 15-89 years). All patients presented with a solitary mass, ranging in size from 1.8 to 12 cm (median 6.8 cm). Seven tumors arose in soft tissue (6 lower limb; 1 upper limb), 5 in the gastrointestinal tract (1 involving both stomach and colon, 1 ileum, 2 rectum, 1 anus), 1 in the nasal cavity, and 1 in the lung. Three gastrointestinal tract tumors also involved regional lymph nodes, and 1 involved the liver. Most cases had infiltrative margins. The tumors were generally composed of sheets of large epithelioid cells with abundant eosinophilic cytoplasm, oval to irregular nuclei, vesicular chromatin, and large nucleoli. Binucleated cells were common, and 6 cases contained tumor giant cells. Mitoses ranged from 1 to 64 per 10 HPF (median 11 per 10 HPF). Necrosis was present in 8 cases. Nearly all tumors showed a striking inflammatory infiltrate, most often of neutrophils or lymphocytes. All cases were reactive for LCA, CD45RO, and CD68 (KP1 and PG-M1); 13 of 14 (93%) expressed CD4, 12 of 14 (86%) lysozyme, 8 of 10 (80%) CD31, 7 of 14 (50%) S-100 protein, and 5 of 14 (36%) focal CD1a. Two tumors showed weak, focal cytoplasmic positivity for CD30, and 1 for epithelial membrane antigen. The tumors were negative for ALK-1, CD21, CD35, CD3, CD20, CD34, myeloperoxidase, HMB-45, and keratins. Gastrointestinal tract cases were negative for c-kit and desmin. Six patients were treated with postoperative radiation and 7 with chemotherapy (CHOP or ProMACE-MOPP). Follow-up was available for 10 patients (median, 24 months; range, 4 months to 11 years). Two tumors recurred locally, and 5 patients developed distant spread: 3 to lymph nodes, 1 to lung, and 1 to bone. At the last follow-up, 2 patients have died of disseminated disease, 4 and 5 months following initial diagnosis. The patients who died thus far had the largest primary tumors. Histiocytic sarcoma may arise primarily in soft tissue and shows reproducible histologic features, including abundant eosinophilic cytoplasm and a prominent inflammatory infiltrate. Metastatic carcinoma, metastatic melanoma, and large cell non-Hodgkin lymphomas should be excluded by immunohistochemistry. Histiocytic sarcoma has the potential for an aggressive clinical course, most often with lymph node involvement. However, a subset of cases presenting with clinically localized disease have a favorable long-term outcome. Tumor size may be a prognostic factor.
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PMID:Extranodal histiocytic sarcoma: clinicopathologic analysis of 14 cases of a rare epithelioid malignancy. 1531 12

The early responses of follicular (Fo) and marginal zone (MZ) B cells to T cell-dependent Ag were compared using anti-hen egg lysozyme (HEL+) B cells capable of class switch recombination and somatic hypermutation (SHM). Purified CD21/(35int)CD23high Fo and CD21/35(high)CD23low MZ splenic B cells from SW(HEL) Ig-transgenic mice were transferred into wild-type recipients and challenged with HEL-sheep RBC. Responding HEL+ B cells from both populations switched efficiently to IgG1, generated syndecan-1+ Ab-secreting cells, and exhibited equivalent rates of proliferation. However, the expansion of HEL+ MZ B cells lagged significantly behind that of HEL+ Fo B cells due to less efficient homing to the outer periarteriolar lymphatic sheath and reduced recruitment into the proliferative response. Despite the equivalent rates of class switch recombination, the onset of SHM was delayed in the MZ subset, indicating that these two activation-induced cytidine deaminase-dependent events are uncoupled in the early response of MZ B cells. Migration of HEL+ B cells into germinal centers coincided with the onset of SHM, occurring more rapidly with Fo vs MZ responders. These results are consistent with the concept that Fo and MZ B cells have evolved to specialize in T cell-dependent and T-independent responses respectively.
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PMID:Altered migration, recruitment, and somatic hypermutation in the early response of marginal zone B cells to T cell-dependent antigen. 1581 78

Tumors of dendritic reticulum cells are rare neoplasms that exhibit significant morphologic overlap with other malignancies. Fine-needle aspiration cytologic appearances of this neoplasm are not well understood. A 33-yr-old woman presented with a rapidly growing nodular mass in the right upper cervical region and right-sided ptosis. Fine-needle aspiration cytology of the mass showed dissociated as well as clustered, large, polygonal cells that showed high nuclear-cytoplasmic ratio. Nuclei were round, oval, or irregular in shape. Large and small blastoid forms with prominent nucleoli and chromatin clumping as well as binucleated cells and cells with lobulated nuclei were seen. Numerous mitoses were observed. The tumor cells expressed focal immunocytochemical reactivity to CD45 and CD68, but were negative for CD2, CD3, CD4, CD8, CD20, CD30, CD45RO, epithelial membrane antigen (EMA), cytokeratin, and HMB45. Histologic sections of the biopsy from the growth showed nodal tissue effaced by a tumor composed of large, pleomorphic neoplastic cells with some binucleate and multinucleate forms resembling Reed-Sternberg cells. The intervening stroma contained numerous small lymphocytes. Tumor cells expressed vimentin, S-100 protein, CD68, and MAC387, but were negative for LCA, CD1a, CD3, CD15, CD20, CD21, CD23, CD30, CD35, carcino-embryonic antigen, HMB45, cytokeratin AE1/3, EMA, myeloperoxidase, lysozyme, smooth-muscle actin, and desmin. The combined histologic and immunohistologic features suggested a histiocytic/dendritic reticulum cell neoplasm and a diagnosis of interdigitating dendritic reticulum cell sarcoma was made.
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PMID:Interdigitating dendritic reticulum cell sarcoma: cytologic, histologic and immunocytochemical features. 1594 93

The adaptive immune response is tightly regulated to limit responding cells in an Ag-specific manner. On B cells, coreceptors CD21/CD19 modulate the strength of BCR signals, potentially influencing cell fate. The importance of the CD95 pathway was examined in response of B cells to moderate affinity Ag using an adoptive transfer model of lysozyme-specific Ig transgenic (HEL immunoglobulin transgene (MD4) strain) B cells. Although adoptively transferred Cr2+/+ MD4 B cells are activated and persist within splenic follicles of duck egg lysozyme-immunized mice, Cr2-/- MD4 B cells do not. In contrast, Cr2-/- MD4 lpr B cells persist after transfer, suggesting that lack of CD21/CD35 signaling results in CD95-mediated elimination. Cr2 deficiency did not affect CD95 levels, but cellular FLIP (c-FLIP) protein and mRNA levels were reduced 2-fold compared with levels in Cr2+/+ MD4 B cells. In vitro culture with Cr2+/+ MD4 B cells demonstrated that equimolar amounts of rHEL-C3d3 were more effective than hen egg lysozyme alone in up-regulating c-FLIP levels and for protection against CD95-mediated apoptosis. Collectively, this study implies a mechanism for regulating B cell survival in vivo whereby the strength of BCR signaling (including coreceptor) determines c-FLIP levels and protection from CD95-induced death.
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PMID:CD21/CD19 coreceptor signaling promotes B cell survival during primary immune responses. 1611 72

A 70-year-old Japanese man presented to our hospital with a 1-month history of progressive general fatigue and anorexia. A physical examination revealed severe anemic condition, mild persistent splenomegaly, and no palpable surface lymph nodes. He had pleural effusion and ascites, though no malignant cells were detected in the effusion. He eventually died without any diagnosis of his disease. Immunohistochemical staining of his tumor after autopsy showed atypical cells that were negative for epithelial membrane antigen (EMA), keratin (AE1/3), keratin-20, vimentin, factor VIII, leukocyte common antigen (LCA/T200; CD45), myeloperoxidase (MPO), terminal deoxynucleotidyl transferase (TdT), lysozyme, CD1a, CD3, CD4, CD10, CD15, CD20 (L26), CD21, CD23, CD34, CD43, CD56, CD68, CD79a, CD138, and EBER-1 in situ. Only a few scattered cells expressed CD30, but they showed no staining for anaplastic large-cell lymphoma kinase (ALK). A few scattered cells expressed S-100 antigen and the majority of cells dominantly expressed dendritic cell-associated antigens (CD35, FDC, Ki-M1p). In conclusion, we found this unknown primary tumor to be consistent with a follicular dendritic cell tumor with anaplastic features.
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PMID:Follicular dendritic cell tumor as an unknown primary tumor. 1738 Apr 43

Lobomycosis (Lacaziosis) occurs only in humans and dolphins under natural conditions. We evaluated the immune status of eight dolphins with lobomycosis and 40 healthy dolphins from the Indian River Lagoon (IRL), Florida. Lobomycosis cases had multiple abnormalities in their immunologic parameters when compared to healthy dolphins. The absolute number of circulating lymphocytes and serum albumin concentration were reduced (P<0.05) while the segmented neutrophils, alpha 1, total beta, total gamma and total globulins were increased (P<0.05). Although innate immunity was relatively intact and phagocytosis and natural killer cell activity were not affected, the plasma lysozyme concentrations were elevated in dolphins with lobomycosis (P<0.05). Adaptive immunity was depressed with statistically significant decreases found in the absolute numbers of CD4(+) helper T cells and CD19(+) and CD21(+) B cells. The ratios of CD2(+) T cells to CD4(+) cells and CD2(+) to CD21(+) cells were increased (P=0.05 and P<0.05, respectively) and the numbers of lymphocytes expressing MHC class II molecules was decreased in dolphins with lobomycosis (P<0.05). Lymphocyte proliferation was reduced in response to stimulation with lipopolysaccharide and concanavalin A (P<0.05). Antibody titers to Erysipelas rhusiopathiae, a common marine micro-organism, were decreased (P<0.05). In summary, dolphins with lobomycosis exhibit significant impairment in adaptive immunity.
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PMID:Immune dysfunction in Atlantic bottlenose dolphins (Tursiops truncatus) with lobomycosis. 1860 90


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