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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus 1 (HIV1) infection is associated with severe psoriasis, B cell lymphoma, and Kaposi's sarcoma. A deregulated production of interleukin 6 (IL-6) has been implicated in the pathogenesis of these diseases. The molecular mechanisms underlying the abnormal IL-6 secretion of HIV1-infected cells may include transactivation of the IL-6 gene by HIV1. To test this hypothesis, we used the pIL6Pr-chloramphenicol acetyltransferase (CAT) plasmid, an IL-6 promoter-CAT construct, as a target of the transactivating function of the HIV1 TAT protein. By cotransfecting the pIL6Pr-CAT and the tat-expressing pSVT8 plasmid in MC3 B-lymphoblastoid or in HeLa epithelial cells, we observed that TAT transactivates the human IL-6 promoter. These results were confirmed when pIL6Pr-CAT was transfected in MC3 or HeLa cells that constitutively expressed the tat gene in a sense (pSVT8 cells) or antisense (pSVT10 cells) orientation. 5' deletion plasmids of pIL6Pr-CAT, in which regions at -658, -287, and -172 were inserted 5' to the cat gene, were transiently transfected in pSVT10 and pSVT8 cells and showed that TAT-induced activation of the IL-6 promoter required a minimal region located between -287 and -54 bp. Moreover, experiments with plasmids carrying the -658, -287, and -172 bp regions of the IL-6 promoter inserted downstream to a TAR-deleted HIV1-LTR identified the sequence of -172 to -54 as the minimal region of the IL-6 promoter required for TAT to transactivate the TAR-deleted HIV1-LTR. By DNA-protein binding experiments, tat-transfected cells expressed a consistent increase in kappa B and nuclear factor (NF)-IL-6 binding activity. Accordingly, the pDRCAT and IL-1REK9CAT, carrying tandem repeats of NF-kappa B or NF-IL6 binding motifs, respectively, were activated in TAT-expressing cells. The biological relevance of the TAT-induced IL-6 secretion was addressed by generating 7TD1 cells, an IL-6-dependent mouse cell line, stably expressing the tat gene. These tat-positive cells expressed the endogenous IL-6 gene, secreted high amounts of murine IL-6, and grew efficiently in the absence of exogenous IL-6. Moreover, the tat-positive 7TD1 cells sustained the growth of parental 7TD1 cells and showed a dramatic increase in their tumorigenic potency. These results suggest that TAT protein may play a role in the pathogenesis of some HIV1-associated diseases by modulating the expression of host cellular genes.
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PMID:The expression of the interleukin 6 gene is induced by the human immunodeficiency virus 1 TAT protein. 811 88

The results of cytogenetic studies are reported in 76 patients with B-chronic lymphoproliferative disorders (B-CLPD): 60 patients with chronic lymphocytic leukemia (CLL), six with follicular lymphoma in leukemic phase (FLLP), five with splenic B-cell lymphoma with villous lymphocytes (SLVL), two with chronic prolymphocytic leukemia (CPL), two with hairy cell leukemia (HCL), and one with plasma cell leukemia (PCL). PHA (phytohemagglutinin), PWM (pokeweed mitogen), LPS (lipopolysaccharide from Escherichia Coli), TPA (phorbol 12-myristate acetate), IL6 (interleukin 6), and DxS (dextran sulfate) were used as mitogens. Mitoses were obtained in 75 cases. Clonal aberrations could be demonstrated in 34 cases (44%). In CLL, classical type, chromosomes 6, 11, and 13 were more frequently involved, whereas trisomy 12 was frequently found in CLL mixed-cell type, in FLLP, and CPL. In SLVL the deletion del(7)(q32) is noteworthy and miscellaneous chromosome abnormalities in the remaining patients were observed. Regarding the efficiency of mitogens, PHA turned to be the most effective in obtaining metaphases and in detecting clonal chromosomal aberrations.
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PMID:Cytogenetic studies in seventy-six cases of B-chronic lymphoproliferative disorders. 907 2

Kaposi's sarcoma (KS)-associated herpesvirus, also known as human herpesvirus 8 (HHV-8), is the first known human member of the genus Rhadinovirus. It is regularly found by polymerase chain reaction in all forms of KS, in certain types of Castleman's disease, and in body cavity-based B-cell lymphoma. Other members of this virus group occur in nonhuman primates, ungulates, rabbits, and mice and cause in part fulminant lymphomas and other neoplastic disorders of the hematopoietic system. Rhadinoviruses share a typical genome structure; most characteristically, they contain numerous sequences that appear to be sequestered from cellular DNA. We cloned and sequenced almost the complete genome of HHV-8 from a single KS biopsy specimen. Although this procedure revealed collinear organization and extensive homologies with the open reading frames of herpesvirus saimiri, genes with homology to the known oncoproteins (Stp, Tip) were not identified in the HHV-8 genome. However, HHV-8 reading frame K1, the positional analogue of Stp/Tip, was found to be significantly variable between different strains. We found, in addition, the reading frames for homologues of cellular interleukin 6, macrophage inflammatory proteins alpha and beta (MIP1 alpha and MIP1 beta, respectively), an interferon-responsive factor, and two inhibitors of apoptosis. Several of these cell-homologous genes of HHV-8 have already been shown to code for functional proteins.
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PMID:Human herpesvirus 8--the first human Rhadinovirus. 970 7

B cell hyperactivation accompanies HIV infection and is believed to contribute to the increased incidence of B cell lymphoma in persons with AIDS. To examine B cell activation which precedes the development of AIDS-associated lymphoma, we measured levels of two B cell stimulatory molecules, soluble CD23 (sCD23) and interleukin 6 (IL6), in the serum of HIV-infected individuals prior to the diagnosis of lymphoma. Serum sCD23 was elevated in those subjects who developed lymphoma, compared to AIDS, HIV+, and HIV- controls (P = 0.001). Serum IL6 was significantly elevated in subjects who developed Burkitt's/small noncleaved cell lymphoma (BL/SNC, P = 0.01), but not in those subjects who developed large cell, immunoblastic, or central nervous system lymphomas, compared to CD4-matched AIDS controls who did not have lymphoma. These results suggest that lymphomagenesis of the BL/SNC subtype of AIDS lymphoma reflects B cell hyperactivation of a different nature from that which precedes other subtypes of AIDS-associated B cell lymphoma.
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PMID:The development of AIDS-associated Burkitt's/small noncleaved cell lymphoma is preceded by elevated serum levels of interleukin 6. 1047 34

A novel cell line, designated OHK, was established from ascites of a 59-year-old Japanese woman with diffuse large B-cell lymphoma showing a peculiar serosal tropism, as seen in primary effusion lymphomas (PEL). OHK exhibited a large pleomorphic morphology with irregular nuclei and distinct nucleoli, and included immunoblastic and Reed-Sternberg-like giant cells. On ultrastructural examination, rich intermediate filaments, and well-developed Golgi apparati and rough endoplasmic reticulum, were seen. Immunophenotypically, OHK lacked T and B cell-associated antigens, and had CD10, CD30, CD33 and CD138 antigens. Although OHK cells did not express immunoglobulin (Ig) protein, Southern blot analysis demonstrated clonal rearrangements of Ig heavy and light chain genes. These observations suggest that OHK cells are derived from preterminally differentiated B cells, and that they have features of PEL. Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus were not detected. OHK displayed hyperploid karyotypes with multiple structural abnormalities, and produced some cytokines such as macrophage-colony-stimulating factor (M-CSF), granulocyte-CSF, interleukin 6 and transforming growth factor beta 1. In particular, vascular endothelial growth factor (VEGF), whose stimulation of vascular permeability is thought to be critical to the pathogenesis of PEL, was also produced in large quantities. These results indicate that OHK may be a useful tool for the investigation of PEL.
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PMID:Establishment and characterization of a Kaposi's sarcoma-associated herpesvirus- and Epstein-Barr virus-negative malignant lymphoma cell line (OHK) with primary effusion lymphoma immunophenotype. 1184 5

Circulating inflammatory cytokines have a prognostic impact independent of the information provided by the International Prognostic Index (IPI) in diffuse large B-cell lymphoma (DLBCL). The present study characterized prognostic cytokines in relation to stage-specific B-cell differentiation antigens and bcl-2 protein expression, assessed by immunohistochemistry in de novo DLBCL. Serum levels of interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) were found to be significantly lower in patients with a germinal centre (GC) phenotype (co-expression of bcl-6 and CD10) compared with the non-GC phenotype. IL-6 and TNF-alpha levels were significantly elevated in patients expressing bcl-2 protein. Serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were not associated with the GC phenotype. On the contrary, both VEGF and bFGF were strongly correlated to bcl-2 expression. In survival analysis, IPI score remained the most important independent prognostic factor. However, IL-6 and VEGF, combined with non-GC phenotype and bcl-2 positivity, respectively, had a similar independent prognostic power as the IPI. In conclusion, our data suggest that inflammatory cytokines are differently distributed in the GC and non-GC phenotypes and correlate to bcl-2 expression. Combining these biomarkers may add to the prognostic information given by clinical variables in the IPI alone.
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PMID:Serum levels of inflammatory cytokines at diagnosis correlate to the bcl-6 and CD10 defined germinal centre (GC) phenotype and bcl-2 expression in patients with diffuse large B-cell lymphoma. 1575 85

Mast cells are pivotal effector cells in IgE-mediated allergic inflammatory diseases. Central for mast cell activation are signals from the IgE receptor FcepsilonRI, which induce cell degranulation with the release of preformed mediators and de novo synthesis of proinflammatory leukotrienes and cytokines. How these individual mast cell responses are differentially controlled is still unresolved. We identify B cell lymphoma 10 (Bcl10) and mucosa-associated lymphoid tissue 1 (Malt1) as novel key regulators of mast cell signaling. Mice deficient for either protein display severely impaired IgE-dependent late phase anaphylactic reactions. Mast cells from these animals neither activate nuclear factor kappaB (NF-kappaB) nor produce tumor necrosis factor alpha or interleukin 6 upon FcepsilonRI ligation even though proximal signaling, degranulation, and leukotriene secretion are normal. Thus, Bcl10 and Malt1 are essential positive mediators of FcepsilonRI-dependent mast cell activation that selectively uncouple NF-kappaB-induced proinflammatory cytokine production from degranulation and leukotriene synthesis.
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PMID:The Bcl10-Malt1 complex segregates Fc epsilon RI-mediated nuclear factor kappa B activation and cytokine production from mast cell degranulation. 1643 53

Kaposi sarcoma-associated herpesvirus (KSHV) causes Kaposi sarcoma and is also associated with primary effusion lymphoma, a subset of diffuse large B-cell lymphomas, and multicentric Castleman disease. Because KSHV infection is endemic in sub-Saharan Africa, we sought to identify cases of KSHV-positive non-Hodgkin lymphomas (NHLs) and reactive lymphadenopathy in this region. One hundred forty-four cases (80 NHLs, 64 reactive lymph nodes) from the major pathology laboratory in Uganda were reviewed. One NHL was KSHV-positive, as indicated by staining for the viral latent nuclear antigen. This NHL was a diffuse large B-cell lymphoma in a 5-year-old boy. The tumor was also Epstein-Barr virus-positive. In addition, 2 reactive lymph nodes, both classified histologically as follicular involution, stained KSHV latent nuclear antigen-positive and thus most likely represent multicentric Castleman disease. In all 3 KSHV-positive cases, a minority of cells expressed KSHV viral interleukin 6, a biologically active cytokine homolog. In conclusion, we show that KSHV is rarely associated with lymphoproliferative disorders in sub-Saharan Africa. We describe the first case of a KSHV-positive NHL from this region; this case is also the first reported pediatric lymphoma associated with KSHV infection.
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PMID:Kaposi sarcoma-associated herpesvirus in non-Hodgkin lymphoma and reactive lymphadenopathy in Uganda. 1709 30

Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling is one of the major pathways for cytokine signal transduction. However, the role of the JAK/STAT pathway in liver ischemia/reperfusion is not clear. This study focuses on Janus kinase-2 (JAK2), which functions upstream of signal transducer and activator of transcription 1 (STAT1) in JAK/STAT, and its role in the mechanism of liver ischemia/reperfusion injury (IRI). Partial warm ischemia was produced in the hepatic lobes of C57BL/6 mice for 90 minutes, and this was followed by 6 hours of reperfusion. Mice were treated with a JAK2 inhibitor (tyrphostin AG490; 40 mg/kg intraperitoneally) or vehicle 60 minutes prior to ischemic insult. JAK2 blockade resulted in a significant reduction of hepatocyte apoptosis and liver injury. Macrophage and neutrophil infiltration, as assessed by immunohistochemistry, was markedly decreased in AG490-treated livers in comparison with controls. The expression of pro-inflammatory cytokines [tumor necrosis factor alpha, interleukin 6 (IL-6), and IL-1beta] and chemokines [chemokine (C-X-C motif) ligand 10 (CXCL-10) and CXCL-2] was also significantly reduced in the AG490-treated group in comparison with controls. AG490-treated livers showed fewer cells positive for terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and reduced cleaved caspase-3 protein expression in parallel with increased B-cell lymphoma extra large expression. We employed AG490 (75 mM) in primary bone marrow-derived macrophage (BMM) and hepatoma cell (CRL1830) cultures, which were both stimulated with lipopolysaccharide (LPS; 10 ng/mL). In BMM cultures, AG490 depressed otherwise LPS-induced pro-inflammatory gene expression programs (IL-6, IL-12p40, IL-1beta, CXCL-10, and inducible nitric oxide synthase). In hepatoma cells, AG490 reduced cleaved caspase-3 expression. Moreover, JAK2 blockade inhibited STAT1 and STAT3 phosphorylation. This is the first report documenting that JAK2 signaling is essential in the pathophysiology of liver IRI, as its selective blockage ameliorated the disease process and protected livers from inflammation and apoptosis.
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PMID:Blockade of Janus kinase-2 signaling ameliorates mouse liver damage due to ischemia and reperfusion. 2111 57

Primary cardiac B-cell lymphoma is an extremely rare heart tumor that may be difficult to diagnose because of nonspecific clinical manifestations. Cardiac myxomas and mediastinal lymphomas show increased levels of serum cytokines, which correlate with symptoms and tumor size. We present a case of an intracardiac large B-cell lymphoma in a 75-year-old woman who had high serum levels of interleukin 6 that decreased after tumor excision. These data suggest a possible correlation between cardiac B lymphoma symptoms and interleukin 6 overproduction.
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PMID:Interleukin 6 activity associated with a cardiac lymphoma. 2044 77


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