Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In agreement with the clonal theory, one B lymphocyte synthesizes one antibody due to allelic and isotypic exclusion. We analyzed an EBV B-cell clone, E29.1, derived from an 11 week-old embryo, and secreting both IgM kappa and IgM lambda. Structural analysis of produced IgM, indicated that lambda-containing pentamers could be considered hybrid molecules, expressing both the kappa and lambda. chains, with a kappa/lambda ratio between 5 and 10. It was also found that 60% of the lambda chains were secreted in free form, presumably as a result of a better affinity of mu chains for kappa chains. The sequence of the three transcripts had an entirely ORF (Open Reading Frame), and were very close to germline sequences, with, however, an additional codon between V kappa and J kappa gene which has never been described in adult myeloma protein or cDNA human sequence. This observation is suggestive of N diversity taking place in kappa chains. The possible role of Kde (kappa deleting element) recombination onto kappa/lambda locus activation was analyzed on a collection of 23 lambda clones. The status of rearrangement of kappa genes indicated that 35% of these clones had retained, at least, one kappa allele without the Kde recombination, four lambda clones had one kappa allele in germline configuration. Different hypotheses of maturation from pre-B cell to B cell with activation of light chain genes are discussed.
 ...
PMID:IGM kappa/lambda EBV human B cell clone: an early step of differentiation of fetal B cells or a distinct B lineage? 138 95

We have cloned and characterized a novel cellular gene that is promoted by an intracisternal A-particle (IAP) LTR and expressed in the mouse placenta (mouse IAP promoted placental gene, MIPP). A 1067bp cDNA clone containing an IAP LTR U5 region duplicated in its 5' terminus and an ORF coding for a potential 202 amino acids protein was isolated from an 8.5 day old mouse embryo cDNA library. Sequence analysis of the 5' region of a genomic clone revealed the presence of a solo IAP LTR with the same U5 duplication, and primer extension analysis confirmed that transcription of the MIPP gene is under the control of the IAP LTR. Expression of the MIPP gene parallels that of IAP genes in normal mouse tissues with abundant transcripts present in the placenta and also in the myeloma MOPC-315. The MIPP-encoded protein is composed of four 48-amino acid repeat units and shares homology with a vaccinia virus gene product. MIPP-related sequences were also detected in higher eukaryotic genomes including human.
 ...
PMID:Identification of a novel murine IAP-promoted placenta-expressed gene. 190 5

A monoclonal antibody (MAb), BLT-1, with specificity for bovine mature T cells was prepared by somatic cell hybridization of myeloma NS-1 and spleen cells from BALB/c mice hyperimmunized with bovine T lymphocytes. The MAb reacted with over 92% of nylon wool-nonadherent lymphocytes (T cells) but not with nylon wool-adherent EAC-positive lymphocytes (B cells) in the indirect immunofluorescence assay. It is an IgM, with kappa-light chains, which fixed complement well and killed over 95% of mature T cells in complement-mediated cytotoxicity assays. It reacted with the same proportions of peripheral lymphoid cells (peripheral blood, lymph nodes, and spleen) as the polyclonal goat anti-bovine thymocyte serum (GABTS), but only with 25% of GABTS-positive thymocytes. Immunoperoxidase staining of frozen tissue sections showed that the BLT-1-positive cells were located in the medulla of the thymus and in the T lymphocyte areas of lymph nodes. Western immunoblotting assays showed that the BLT-1-reactive membrane antigen is a 22,000 m.w. protein which was inducible in bovine thymocytes with bovine thymic hormones, thymosin fraction 5, thymosin alpha 1, and thymopentin ORF-18150, indicating that it is a mature T lymphocyte differentiation antigen. The thymosin alpha 1 and thymopentin were found to show additive effects on mature T cell antigen expression by bovine thymocytes.
 ...
PMID:Production and characterization of a bovine T cell-specific monoclonal antibody identifying a mature differentiation antigen. 307 88

We have recently demonstrated the presence of Kaposi's sarcoma-associated herpesvirus (KSHV) in cultured bone marrow (BM) stromal dendritic cells from all patients with myeloma studied. To show that these findings were not an artifact of tissue culture, we performed in situ hybridization (ISH) and polymerase chain reaction (PCR) to detect KSHV in BM core biopsies. Using ISH to open reading frame-72 (ORF 72), we localized KSHV to BM dendritic cells in 17 of 20 patients with myeloma, 2 patients with plasmacytosis associated with the acquired immunodeficiency syndrome, and 1 case of aplastic anemia. In contrast, BM from normal subjects (n = 4) and patients with lymphoma and leukemia (n = 21) did not contain KSHV. PCR amplification with KSHV primers demonstrated product in fresh BM biopsy samples from 6 of 7 myeloma patients, whereas three normal marrows contained no amplified product. These findings suggest that KSHV, possibly through alterations in the BM microenvironment and production of viral interleukin-6 (vIL-6), may stimulate and maintain abnormal plasma cell proliferation in myeloma and related disorders.
 ...
PMID:Localization of Kaposi's sarcoma-associated herpesvirus in bone marrow biopsy samples from patients with multiple myeloma. 978 98

Whether Kaposi's sarcoma herpesvirus (KSHV) is associated with multiple myeloma (MM) remains controversial. We assayed for KSHV DNA sequences in long-term bone marrow stromal cells (BMSCs) from 26 patients with MM and 4 normal donors. Polymerase chain reaction (PCR) using primers which amplify a KSHV gene sequence to yield a 233-bp fragment (KS330233 within open reading frame 26) was negative in all cases. Aliquots of these PCR products were used as templates in subsequent nested PCR, with primers that amplify a 186-bp product internal to KS330233. BMSCs from 24 of 26 (92%) patients with MM and 1 of 4 normal donors were KSHV PCR+. DNA sequence analyses showed interpatient specific mutations (2 to 3 bp). Both Southern blot and sequence analyses confirmed the specificity of PCR results. The presence of the KSHV gene sequences was further confirmed by amplifying T 1.1 (open reading frame [ORF] K7) and viral cyclin D (ORF 72), two other domains within the KSHV genome. Immunohistochemical studies of KSHV PCR+ MM BMSCs demonstrate expression of dendritic cell (DC) lineage markers (CD68, CD83, and fascin). Serological studies for the presence of KSHV lytic or latent antibodies were performed using sera from 53 MM patients, 12 normal donors, and 5 human immunodeficiency virus (HIV)/KSHV+ patients. No lytic or latent antibodies were present in sera from either MM patients or normal donors. Taken together, these findings show that KSHV DNA sequences are detectable in BMSCs from the majority of MM patients, but that serologic responses to KSHV are not present. Ongoing studies are defining whether the lack of antibody response is caused by the absence of ongoing infection, the presence of a novel viral strain associated with MM, or underlying immunodeficiency in these patients.
 ...
PMID:Detection of Kaposi's sarcoma herpesvirus DNA sequences in multiple myeloma bone marrow stromal cells. 1002 74

Multiple myeloma (MM) cells express idiotypic proteins and other tumor-associated antigens which make them ideal targets for novel immunotherapeutic approaches. However, recent reports show the presence of Kaposi's sarcoma herpesvirus (KSHV) gene sequences in bone marrow dendritic cells (BMDCs) in MM, raising concerns regarding their antigen-presenting cell (APC) function. In the present study, we sought to identify the ideal source of DCs from MM patients for use in vaccination approaches. We compared the relative frequency, phenotype, and function of BMDCs or peripheral blood dendritic cells (PBDCs) from MM patients versus normal donors. DCs were derived by culture of mononuclear cells in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. The yield as well as the pattern and intensity of Ag (HLA-DR, CD40, CD54, CD80, and CD86) expression were equivalent on DCs from BM or PB of MM patients versus normal donors. Comparison of PBDCs versus BMDCs showed higher surface expression of HLA-DR (P =.01), CD86 (P =. 0003), and CD14 (P =.04) on PBDCs. APC function, assessed using an allogeneic mixed lymphocyte reaction (MLR), demonstrated equivalent T-cell proliferation triggered by MM versus normal DCs. Moreover, no differences in APC function were noted in BMDCs compared with PBDCs. Polymerase chain reaction (PCR) analysis of genomic DNA from both MM patient and normal donor DCs for the 233-bp KSHV gene sequence (KS330233) was negative, but nested PCR to yield a final product of 186 bp internal to KS330233 was positive in 16 of 18 (88.8%) MM BMDCs, 3 of 8 (37.5%) normal BMDCs, 1 of 5 (20%) MM PBDCs, and 2 of 6 (33.3%) normal donor PBDCs. Sequencing of 4 MM patient PCR products showed 96% to 98% homology to the published KSHV gene sequence, with patient specific mutations ruling out PCR artifacts or contamination. In addition, KHSV-specific viral cyclin D (open reading frame [ORF] 72) was amplified in 2 of 5 MM BMDCs, with sequencing of the ORF 72 amplicon revealing 91% and 92% homology to the KSHV viral cyclin D sequence. These sequences again demonstrated patient specific mutations, ruling out contamination. Therefore, our studies show that PB appears to be the preferred source of DCs for use in vaccination strategies due to the ready accessibility and phenotypic profile of PBDCs, as well as the comparable APC function and lower detection rate of KSHV gene sequences compared with BMDCs. Whether active KSHV infection is present and important in the pathophysiology of MM remains unclear; however, our study shows that MMDCs remain functional despite the detection of KSHV gene sequences.
 ...
PMID:Bone marrow and peripheral blood dendritic cells from patients with multiple myeloma are phenotypically and functionally normal despite the detection of Kaposi's sarcoma herpesvirus gene sequences. 1002 75

Bone marrow (BM) from patients affected by multiple myeloma (MM), exhibiting monoclonal gammopathy of undetermined significance (MGUS) or with non-Hodgkin lymphoma (NHL) as well as from healthy donors were investigated for the presence of human herpesvirus-8 (HHV-8) DNA sequences. ORF 26 sequences were detected in 36--56% of the patients and in 29% of the controls. In a few cases, two other HHV-8 DNA sequences were also detected. These observations indicate that the presence of the HHV-8 genome in BM is relatively common in different groups of patients as well as in healthy individuals and do not support an alleged role for HHV-8 in MM.
 ...
PMID:Human herpesvirus 8 DNA sequences are present in bone marrow from HIV-negative patients with lymphoproliferative disorders and from healthy donors. 1132

It has been proposed that the absence of a humoral response to human herpes virus 8 (HHV-8) in patients with multiple myeloma (MM) reflects strain variation or the mutation, or absence, of the antigenic regions of HHV-8 recognized in ELISA screening tests. We therefore assessed DNA sequence of three antigenic regions (ORF65, ORF73 and ORFK8.1) and the transforming hypervariable K1 ORF of HHV-8 in fresh bone marrow cells, bone marrow derived dendritic cells (DCs) and bone marrow stromal cells (BMSCs) from 12 patients with MM and 8 normal individuals. HHV-8 ORFs were detectable by nested PCR in MM patients (ORF65: 67% ORF73: 22% and K8.1: 58%), but were also surprisingly frequent in normal individuals (ORF65: 37%, ORF73: 12.5% and K8.1: 62%). HHV-8 sequences were more frequently detected in cells from BMSC and DC culture than from fresh bone marrow in MM. In contrast no HHV-8 sequences were detected in BMSC from normal individuals. Sequence analysis of ORF65 failed to demonstrate productive mutations in any MM sample. K1 genomic sequences were detected in 42% of MM and 37% of normals and exhibited 98% homology with the K1-A1 HHV-8 strain. In conclusion, our data do not support the presence of a K1-C3 strain of HHV-8 with ORF65 expression deficiency in MM patients. HHV-8 infection appears to be common in the general population when sensitive PCR is employed and multiple samples are analyzed.
 ...
PMID:Antigenic open reading frames from HHV-8 are present in multiple myeloma patients and normal individuals at similar frequency. 1199 72

In our previous studies, DAZAP2 gene expression was down-regulated in untreated patients of multiple myeloma (MM). For better studying the structure and function of DAZAP2, a full-length cDNA was isolated from mononuclear cells of a normal human bone marrow, sequenced and deposited to Genbank (AY430097). This sequence has an identical ORF (open reading frame) as the NM_014764 from human testis and the D31767 from human cell line KG-1. Phylogenetic analysis and structure prediction reveal that DAZAP2 homologues are highly conserved throughout evolution and share a polyproline region and several potential SH2/SH3 binding sites. DAZAP2 occurs as a single-copy gene with a four-exon organization. We further noticed that the functional DAZAP2 gene is located on Chromosome 12 and its pseudogene gene is on Chromosome 2 with electronic location of human chromosome in Genbank, though no genetic abnormalities of MM have been reported on Chromosome 12. The ORF of human DAZAP2 encodes a 17-kDa protein, which is highly similar to mouse Prtb. The DAZAP2 protein is mainly localized in cytoplasm with a discrete pattern of punctuated distribution. DAZAP2 may associate with carcinogenesis of MM and participate in yet-to-be identified signaling pathways to regulate proliferation and differentiation of plasma cells.
 ...
PMID:The structure, expression and function prediction of DAZAP2, a down-regulated gene in multiple myeloma. 1562 43

Type I interferons and interferon regulatory factor 7 (IRF7), which are crucial for innate immunity against viral infection, have been identified in many teleost fishes in recent years. In this study, the complete genomic sequence of grass carp (Ctenopharyngodon idella) type I interferon (termed CiIFN) (GU139255) and the full-length IRF7 cDNA sequence of grass carp (termed CiIRF7) (GQ141741) were cloned and characterized. CiIFN consists of 3368 bp, retaining the characteristic 5-exon/4-intron gene organization in fish type I IFNs. The CiIFN spans 5 exons and encodes a polypeptide of 180 amino acids, with the first 22 amino acids representing a putative signal peptide. The CiIFN promoter sequence was found to be 760 bp, which can be divided into a proximal region (from -1 to -140 bp) and a distal region (from -400 to -700 bp). The cDNA of CiIRF7 was found to be 1808 bp in full length, with an ORF of 1293 bp that encodes a putative protein of 430 amino acids. The putative amino acid sequence of CiIRF7 possesses a DNA-binding domain (DBD) in the N-terminal region. Real-time PCR analysis revealed that CiIFN displayed a low constitutive expression in all the tissues tested. After stimulation by polyinosinic:polycytidylic acid (Poly I:C), the expression of CiIFN was significantly up-regulated in most tissues of grass carp, with a relatively strong expression in spleen, kidney and intestine. The recombinant polypeptides of CiIRF7 and CiIRF7-nDBD were analyzed in gel mobility shift assays, along with the PCR amplification products of the proximal region (CiIFNP2), the distal region (CiIFNP6) and the full-length (CiIFNP7) of CiIFN promoter sequence. The results revealed that CiIRF7 could bind to the distal region as well as to the proximal region of CiIFN promoter sequence in vitro. Subsequently, the CiIFNPs (CiIFNP7/2/6) were cloned into pGL3-Basic vectors and CiIRF7 was subcloned into pcDNA3.1 vectors, then pGL3-CiIFNPs were separately transiently transfected or co-transfected with pcDNA3.1-CiIRF7 into the mouse myeloma cell lines (MMCL) SP2/0 and the grass carp kidney cell lines (CIK), and the impact of CiIRF7 on CiIFN promoter activity was measured by luciferase assays in the transfected cells. These results demonstrated that CiIRF7 acted as a positive regulator on the transcription of CiIFN.
 ...
PMID:Molecular characterization and transcription regulation analysis of type I IFN gene in grass carp (Ctenopharyngodon idella). 2257 63


1 2 Next >>