Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Escherichia coli hemolysin (HlyA) and Pasteurella haemolytica leukotoxin (LktA) are cytolytic toxins encoded by genes belonging to the recently described RTX gene family. These cytotoxins are, respectively, 1,023 and 953 amino acids in length and are encoded by genes within identically organized operons. They share 45% amino acid sequence identities but differ in their target cell specificities. In vitro-derived recombinant hybrid genes between hlyA and lktA were constructed by using restriction endonuclease sites created by oligonucleotide site-directed mutagenesis. The cytolytic activity of hybrid proteins was investigated using as targets sheep erythrocytes and two cultured cell lines from different species (BL3, bovine leukemia-derived B lymphocytes; and Raji, human B-cell lymphoma cells). HlyA is cytolytic to all three cell types. LktA lyses only BL3 cells. Among the hybrid proteins displaying cytolytic activity, the striking finding is that the hemolytic activity of several LktA-HlyA hybrids was independent of any cytolytic activity against either cultured cell species. The hemolytic activity was associated with the HlyA region between amino acids 564 and 739. Structures that are critical for HlyA cytolytic activity against BL3 or Raji cells were destroyed when LktA-HlyA and HlyA-LktA hybrids were made, respectively, at amino acid positions 564 and 739 of HlyA. In contrast to HlyA, which lysed the two different cultured cell lines with equal efficiency, Lkt-HlyA hybrids possessing the amino-terminal 169 residues of LktA lysed BL3 cells more efficiently than Raji cells. This suggests that a significant but not exclusive element of the LktA ruminant cell specificity resides in the amino-terminal one-fifth of the protein. A molecular model of the functional domains of HlyA and LktA is presented.
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PMID:Identification of RTX toxin target cell specificity domains by use of hybrid genes. 193 78

To investigate bovine leukemia virus (BLV)-induced leukemogenesis, we infected sheep with BLV and used flow-cytometric and immunohistological analysis to characterize the phenotypic alterations in lymphocytes from peripheral blood and lymph nodes taken from the animals with lymphoma at various stages. In sheep at the asymptomatic stage, depending on the extent of progression of the disease, the proportions of CD2(+)-, CD4(+)-, CD8(+)-, and gamma delta TCR(+)-T cells that coexpressed CD5 decreased, but CD5+ sIgM+ cells as well as CD5- sIgM+ cells increased for a period. The number of CD5+ B cells, however, rapidly decreased in the lymphoma stage. On the other hand, neoplastic lymphocytes appeared to be a monoclonal population derived from a single cell with surface phenotypes of sIgM+, B-cell-specific molecule B2+, major histocompatibility complex (MHC) class II+, OvCD5-, OvCD2-, OvCD4-, OvCD8-, gamma delta TCR-, which suggests that only CD5- B cells proliferate clonally when the disease proceeds to the lymphoma stage. Thus, rapid decrease of CD5+ B cells may be used as a marker of lymphoma stage. To identify the BLV provirus in the CD5- B and CD5+ B cells throughout the course of disease, each fraction of CD5- B and CD5+ B cell was sorted from the peripheral blood by flow cytometry and nested double polymerase chain reaction was performed. In BLV-infected but healthy sheep, BLV integrated both CD5- B and CD5+ B cells. In lymphoma, however, BLV provirus was detected only in CD5- B cells but not in CD5+ B cells. Therefore it appears that a disappearance of BLV-infected CD5+ cells is one of the critical events leading to CD5- B cell lymphoma in sheep. This is in contrast to the BLV-induced lymphoma in cattle which shows CD5+ phenotype.
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PMID:Bovine leukemia virus induces CD5- B cell lymphoma in sheep despite temporarily increasing CD5+ B cells in asymptomatic stage. 751 99

Monoclonal antibody c143 against tumor-associated antigen (TAA) expressed on bovine leukemia cells was conjugated to cationic liposomes carrying a plasmid pLTR-DT which contained a gene for diphtheria toxin A-chain (DT-A) under the control of the long terminal repeat (LTR) of bovine leukemia virus (BLV) in the multicloning site of pUC-18. The specificity and antitumor effects of the conjugates were examined in vitro and in vivo using TAA-positive bovine B-cell lymphoma line as the target tumor. In vitro studies with the TAA-positive cell line indicated that luciferase gene-containing cationic liposomes associated with the c143 anti-TAA monoclonal antibody caused about 2-fold increase in luciferase activity compared with cationic liposomes having no antibody, and also that the c143-conjugated cationic liposomes containing pLTR-DT exerted selective growth-inhibitory effects on the TAA-positive B-cell line. Three injections of pLTR-DT-containing cationic liposomes coupled with c143 into tumor-bearing nude mice resulted in significant inhibition of the tumor growth. The antitumor potency of the c143-conjugated cationic liposomes containing pLTR-DT was far greater than that of normal mouse IgG-coupled cationic liposomes containing pLTR-DT as assessed in terms of tumor size. These results suggest that cationic liposomes bearing c143 are an efficient transfection reagent for BLV-infected B-cells lymphoma cells, and that the delivery of the pLTR-DT gene into BLV-infected B-cells by the use of such liposomes may become a useful technique for gene therapy of bovine leukosis.
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PMID:Antitumor effect of diphtheria toxin A-chain gene-containing cationic liposomes conjugated with monoclonal antibody directed to tumor-associated antigen of bovine leukemia cells. 991 90

Spleen tyrosine kinase (Syk) is closely related to various cell reactions. In B-cells, Syk is involved in early B-cell receptor signaling, which affects cellular survival, proliferation and differentiation. Although the kinetics of Syk mRNA and its activity are variable in different types of tumor cells, Syk may have a relation to tumor progression in many human tumors, including B-cell lymphoma/leukemia. In this study we examined whether Syk mRNA expression was changed in bovine leukemia virus (BLV)-induced persistent lymphocytosis (PL) and lymphoma. As a result, we demonstrated that the Syk mRNA expression was significantly increased in PL samples, whereas it was decreased in tumor samples. Moreover one cow, which Syk mRNA expression has been lowest among PL cattle, developed lymphoma three months later and the expression significantly decreased. These data suggest that Syk mRNA expression dynamics is closely related to BLV-induced disease.
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PMID:Analysis of Syk expression in bovine lymphoma and persistent lymphocytosis induced by bovine leukemia virus. 2073 17

Multicentric B-cell lymphoma with extensive retrobulbar involvement was diagnosed in a 6-year-old Nubian goat that was presented with conjunctival swelling and exophthalmos. Serologic testing for bovine leukemia virus (BLV) was negative. Postmortem computed tomography aided in identification of the extent of soft tissue and bone lesions.
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PMID:Exophthalmos due to multicentric B-cell lymphoma in a goat. 2265 43

Bovine leukemia virus (BLV) induces abnormal B-cell proliferation and B-cell lymphoma in cattle, where the BLV provirus is integrated into the host genome. BLV-infected B-cells rarely express viral proteins in vivo, but short-term cultivation augments BLV expression in some, but not all, BLV-infected B-cells. This observation suggests that two subsets, i.e. BLV-silencing cells and BLV-expressing cells, are present among BLV-infected B-cells, although the mechanisms of viral expression have not been determined. In this study, we examined B-cell markers and viral antigen expression in B-cells from BLV-infected cattle to identify markers that may discriminate BLV-expressing cells from BLV-silencing cells. The proportions of IgM(high) B-cells were increased in blood lymphocytes from BLV-infected cattle. IgM(high) B-cells mainly expressed BLV antigens, whereas IgM(low) B-cells did not, although the provirus load was equivalent in both subsets. Several parameters were investigated in these two subsets to characterize their cellular behaviour. Real-time PCR and microarray analyses detected higher expression levels of some proto-oncogenes (e.g. Maf, Jun and Fos) in IgM(low) B-cells than those in IgM(high) B-cells. Moreover, lymphoma cells obtained from the lymph nodes of 14 BLV-infected cattle contained IgM(low) or IgM(-) B-cells but no IgM(high) B-cells. To our knowledge, this is the first study to demonstrate that IgM(high) B-cells mainly comprise BLV-expressing cells, whereas IgM(low) B-cells comprise a high proportion of BLV-silencing B-cells in BLV-infected cattle.
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PMID:Differences in cellular function and viral protein expression between IgMhigh and IgMlow B-cells in bovine leukemia virus-infected cattle. 2481 26

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis, a malignant B cell lymphoma. BLV has spread worldwide and causes serious problems. After infection, the BLV genome is integrated into the host DNA and can be amplified during periods of latency. We previously designed degenerate primers using the Coordination of Common Motifs (CoCoMo) algorithm to establish a new quantitative real-time PCR method (BLV-CoCoMo-qPCR-2) of measuring the proviral load of both known and novel BLV variants. Here, we aimed to examine the correlation between proviral load and risk factors for BLV infection, such as breeding systems, parousity, and colostrum feeding. Blood and serum samples were collected from 83 BLV-positive farms in 22 prefectures of Japan, and the BLV proviral load and anti-BLV antibody levels were measured. BLV was detected in 73.3% (1039/1,417) of cattle by BLV-CoCoMo-qPCR-2 and the provirus was detected in 93 of 1039 antibody-negative samples. The results showed that the proviral load increased with progression of lymphocytosis. Next, the risk factors associated with increasing BLV infection rate were examined along with any association with proviral load. The proviral load was higher in cattle with lymphocytosis than in healthy cattle, and higher in multiparous cows than in nulliparous cows. Finally, proviral loads were higher in contact breeding systems than in non-contact breeding systems. Taken together, these findings may help to formulate a plan for eliminating BLV from contaminated farms. This is the first nationwide study to estimate BLV proviral load in Japanese cattle.
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PMID:Risk factors associated with increased bovine leukemia virus proviral load in infected cattle in Japan from 2012 to 2014. 2632 Nov 60

We describe a B-cell lymphoma of a submandibular lymph node with metastasis to the lung and facial subcutaneous tissues in a water deer ( Hydropotes inermis ). Neoplastic cells contained pleomorphic lymphocytes that were positive for CD79a, consistent with B-cell lymphoma. PCR for bovine leukemia virus was negative.
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PMID:Primary B-Cell Lymphoma of Submandibular Lymph Node in a Water Deer ( Hydropotes inermis ). 2705 69

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis, a malignant B cell lymphoma that has spread worldwide and causes serious problems for the cattle industry. The BLV proviral load, which represents the BLV genome integrated into host genome, is a useful index for estimating disease progression and transmission risk. Here, we conducted a genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with BLV proviral load in Japanese Black cattle. The study examined 93 cattle with a high proviral load and 266 with a low proviral load. Three SNPs showed a significant association with proviral load. One SNP was detected in the CNTN3 gene on chromosome 22, and two (which were not in linkage disequilibrium) were detected in the bovine major histocompatibility complex region on chromosome 23. These results suggest that polymorphisms in the major histocompatibility complex region affect proviral load. This is the first report to detect SNPs associated with BLV proviral load in Japanese Black cattle using whole genome association study, and understanding host factors may provide important clues for controlling the spread of BLV in Japanese Black cattle.
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PMID:Single nucleotide polymorphisms in the bovine MHC region of Japanese Black cattle are associated with bovine leukemia virus proviral load. 2837 81

Bovine leukemia is classified into two types: enzootic bovine leukosis (EBL) and sporadic bovine leukosis (SBL). EBL is caused by infection with bovine leukemia virus (BLV), which induces persistent lymphocytosis and B-cell lymphoma in cattle after a long latent period. Although it has been demonstrated that BLV-associated lymphoma occurs predominantly in adult cattle of >3 to 5 years, suspicious cases of EBL onset in juvenile cattle were recently reported in Japan. To investigate the current status of bovine leukemia in Japan, we performed immunophenotypic analysis of samples from 50 cattle that were clinically diagnosed as having bovine leukemia. We classified the samples into five groups on the basis of the analysis and found two different types of EBL: classic EBL (cEBL), which has the familiar phenotype commonly known as EBL, and polyclonal EBL (pEBL), which exhibited neoplastic proliferation of polyclonal B cells. Moreover, there were several atypical EBL cases even in cEBL, including an early onset of EBL in juvenile cattle. A comparison of the cell marker expressions among cEBL, pEBL, and B-cell-type SBL (B-SBL) revealed characteristic patterns in B-cell leukemia, and these patterns could be clearly differentiated from those of healthy phenotypes, whereas it was difficult to discriminate between cEBL, pEBL, and B-SBL only by the expression patterns of cell markers. This study identified novel characteristics of bovine leukemia that should contribute to a better understanding of the mechanism underlying tumor development in BLV infection.
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PMID:Identification of an Atypical Enzootic Bovine Leukosis in Japan by Using a Novel Classification of Bovine Leukemia Based on Immunophenotypic Analysis. 2974 49


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