Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0220723 (PCA)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD45 is the most common protein tyrosine phosphatase (PTPase) in the membrane of white blood cells, serving as a potent regulator of lymphocyte activation and signal transduction. While the amino acid sequence of the intracellular domain of the molecule is conserved, that of the extracellular domain occurs in multiple isoforms, each of the result of alternative mRNA splicing. In T lymphocytes, the lowest relative molecular mass (Mr) form, CD45RO, is associated with acquisition of memory function, whereas the highest Mr isoform, CD45RA, occurs in "naive" T cells. Recently, B cells were also found to express CD45RO following in vitro activation. In order to more fully characterize the expression of CD45 on activated B cells, we have studied its appearance on Epstein-Barr virus-transformed (EBV-t) cells and have found heterogeneous expression of CD45RO and CD45RA. CD45RO expression was unstable with eventual loss by some EBV-t lines, and loss followed by reappearance in others. CD45RA and CD45RO varied independently whereas CD45 remained stable and high, suggesting a fluctuation in other CD45 isoforms. Immunostaining for CD45RB indicates that a probable 190-kDa isoform may be responsible for this observation. A similar bidirectional reversible shifting between CD45RA and CD45RO on T-cell lines has also been reported by Rothstein et al. In contrast to some reports on normal B cells, neither CD45RA nor CD45RO expression was associated with PCA-1 expression. Further evidence that these EBV-t lines may not correspond to a well-defined stage of B-cell differentiation is provided by the observation that a disproportionate loss of CD20 compared to CD19 was noted for several lines. The basis for the CD45 isoform switching, or any functional difference(s) in the expressed isoforms, is not yet known for human B cells.
 ...
PMID:Expression of CD45 isoforms by Epstein-Barr virus-transformed human B lymphocytes. 137 Feb 60

The role of interleukin 6 (IL-6) in the growth of five multiple myeloma-derived cell lines was characterized. The U266 and RPMI 8226 cell lines demonstrated increased DNA synthesis when cultured with exogenous IL-6, expressed IL-6 cell surface receptors (IL-6Rs) and expressed mRNA for IL-6R. However, these cells did not secrete detectable IL-6 protein, and a neutralizing antibody to IL-6 did not inhibit their growth. Three other myeloma-derived cell lines ARH-77, IM-9 and HS-Sultan did not respond to exogenous IL-6, secrete IL-6 or express cell surface IL-6Rs. The IL-6 responsive cell lines bore late B-cell surface antigens (Ags), CD38 and PCA-1, whereas those lines which were non-IL-6 responsive strongly expressed B1 (CD20) and B4 (CD19) Ags, representing earlier stages in B-cell differentiation. Finally, the two IL-6 responsive cell lines did not express Epstein-Barr virus (EBV) proteins; in contrast, EBV encoded proteins typically expressed during latency could be detected in the three non-IL-6 responsive lines, confirming infection with virus. These studies clarify the heterogeneity observed in the myeloma cell line phenotype and biology and suggest that the U266 and RPMI 8226 cell lines, which express IL-6 cell surface receptors and are IL-6 responsive, may be useful for further study of IL-6 signal transduction in and related IL-6 mediated growth of myeloma in vivo. In contrast, those cell lines which are IL-6-independent provide a model for further study of EBV transformation and IL-6-dependent growth mechanisms in malignancy.
 ...
PMID:Role of interleukin 6 in the growth of myeloma-derived cell lines. 140 8

A new human plasma cell line, UMJF-2, has been derived from the bone marrow of a patient with multiple myeloma. Morphological studies disclosed large nucleoli, moderate numbers of mitochondria, and scant endoplasmic reticulum consistent with a plasmablastic morphology. The cells have immunologic characteristics of early plasma cells, including intense expression of cytoplasmic IgG-lambda and weaker, but discernible, expression of surface IgG-lambda. Cell surface antigens defined by the monoclonal antibodies OKT10 (CD38) and PCA-1, characteristic of mature plasma cells, and B1 (CD20), B4 (CD19), and I-2 (HLA-DR), characteristic of earlier stages of B-lymphocyte differentiation, are present on UMJF-2 cells. Cytogenetic studies reveal the presence of trisomy 12. UMJF-2 does not contain the Epstein-Barr virus by Southern blot analysis. Tissue culture media conditioned by these cells contains a soluble immunosuppressive factor, capable of inhibiting pokeweed mitogen induced IgM secretion by normal human B-lymphocytes. UMJF-2 provides a model for the study of the pathogenesis of polyclonal hypogammaglobulinemia in human multiple myeloma.
 ...
PMID:Characterization of a new human multiple myeloma cell line, UMJF-2, which suppresses antibody production by B-lymphocytes in vitro. 164 57

A new human myeloma cell line NOP-2, producing immunoglobulin (Ig)-lambda-light chain was established from a patient with Bence Jones-type multiple myeloma. Morphologically, the cell line had plasmacytoid characteristics by light- and electron-microscopic examination. Phenotypic studies of NOP-2 cells revealed no surface Ig, but they were positive for cytoplasmic Ig-lambda, OKT10 (CD 38), and PCA-1. Epstein-Barr nuclear antigen was not detected. Chromosomal abnormalities of t(11;14) and t(8;22) were found in both NOP-2 cells and the original myeloma cells obtained from the patient. NOP-2 cells produced and secreted Ig-lambda light chain, but lacked immunoglobulins of any heavy chains. Rearrangements of both immunoglobulin heavy- and light-chain genes were observed in NOP-2 cells, though the cells expressed detectable mRNA only for Ig-lambda light chain. This cell line may serve as a useful model for understanding the hierarchy of human immunoglobulins and the pathophysiology of Bence Jones-type multiple myeloma.
 ...
PMID:Establishment and characterization of a new human Bence Jones-type myeloma cell line, NOP-2. 174 47

Four human myeloma cell lines (MM-S1, MM-A1, MM-Y1 and MM-C1) were established from patients in the terminal stage of multiple myeloma. All the cell lines were PCA-1 positive and three were CD38 (OKT10) positive. The class of cytoplasmic immunoglobulin in each of these cell lines was identical to that of the monoclonal protein detected in each patient. Epstein-Barr virus nuclear antigen was negative in all cell lines. An examination of the tritiated thymidine uptake showed that all four cell lines proliferated in response to interleukin-6 (IL-6), while MM-S1 also responded to IL-5. Immunological staining with an anti-IL-6 receptor monoclonal antibody revealed the presence of receptors for IL-6 on the cells from each cell line. Three of them formed colonies dependent on IL-6 in methylcellulose semi-solid culture. All four cell lines grew better when human plasma was added as a supplement to the culture in comparison to fetal calf serum. Northern blot analysis showed that the three cell lines tested did not express IL-6 messenger RNA. These results indicate that these four cell lines are responsive to IL-6, but not by an autocrine mechanism, at least in the three lines examined.
 ...
PMID:Establishment and characterization of four myeloma cell lines which are responsive to interleukin-6 for their growth. 207 43

Using a serum-free defined medium, we have established a human cell line, NCI-H929, from a malignant effusion occurring in a patient with IgAk myeloma. The cultured cells have the morphologic, ultrastructural, biochemical, immunologic, and cytochemical features of plasma cells. The cells have rearranged alpha and kappa genes and synthesize and secrete high amounts of IgAk (greater than 80 micrograms/10(6) cells per 24 hours). The cells express surface immunoglobulin (alpha and kappa), the plasma cell antigen PCA-1, the transferrin receptor (T9) and T10 but lack antigens associated with earlier stages of B cell development (HLA-DR, B1, B2, B4, CALLA), as well as other leukocyte-macrophage antigens and Epstein-Barr virus (EBV) nuclear antigen. Although molecular studies confirm that both the tumor and cultured cells are derived from the same clone of malignant B cells, the tumor cells were predominantly near-diploid, whereas the cultured cells are predominantly near-tetraploid with six copies of chromosome 8, four to six of which have an 8q + abnormality. However, both the tumor and the cultured cells have a rearrangement of the cellular c-myc proto-oncogene (located at 8q24) and express c-myc RNA. Although a modest number of human "plasmacytoid" cell lines have been established, most are lymphoblastoid lines lacking plasma cell features, while others appear to be early secretory cells. In contrast, NCI-H929 is a differentiated, highly secretory human plasma cell line.
 ...
PMID:Establishment and characterization of a human plasma cell myeloma culture having a rearranged cellular myc proto-oncogene. 242 57

Two stable lines of IgA lambda-producing plasma cells (KHM-1A and KHM-1B) that were free of the Epstein-Barr virus were established from a patient with multiple myeloma complicated by hyperamylasemia. Surface marker studies of the two cell lines showed that the cells had no surface immunoglobulins but were positive for cytoplasmic immunoglobulins (IgA lambda) and for HLA-DR and PCA-1. Secretion of IgA monoclonal immunoglobulin by the two lines was detected by a plaque-forming cell assay and by an enzyme-linked immunosorbent assay of culture media. KHM-1B cells also secreted alpha-amylase, but no such activity was detected in the culture-conditioned supernatant fluid of KHM-1A.
 ...
PMID:Establishment and characterization of an amylase-producing human myeloma cell line. 245 53

A small number of human myelomas have been established as long term cultured cell lines. We report the characteristics of two new cell lines, designated SK-MM-1 and SK-MM-2, derived from 73 attempts to culture myeloma specimens. Both cell lines were grown from myeloma patients with hypogammaglobulinemia, kappa light chain proteinuria, and plasma cell leukemia. SK-MM-1 and SK-MM-2 had a plasmacytoid morphology, grew in RPMI complete medium with doubling times of 32 and 60 hr, respectively, and did not express Epstein-Barr virus nuclear antigen. Both cell lines secreted kappa light chains (0.9 and 1.1 micrograms/10(6) cells/ml per 48 hr for SK-MM-1 and SK-MM-2, respectively) but no heavy chains. SK-MM-1 and SK-MM-2 expressed the pan-B cell marker B1 and the late B cell/plasma cell marker BL3. In addition, SK-MM-2 expressed late B cell/plasma cell markers OKT10 and PCA-1. Neither cell line expressed T lymphocyte, myeloid, or early B lymphocyte markers. The presence of distinctive kappa and heavy chain gene rearrangements supported the clonal origin of both cell lines from kappa light chain-producing B cells. The two cell lines were markedly aneuploid and both carried a 14q+ marker chromosome. Human myeloma cell lines lacking heavy chain secretion may be useful to elucidate mechanisms of immunoglobulin gene regulation and to construct human-human hybridomas.
 ...
PMID:Establishment and characterization of two human myeloma cell lines secreting kappa light chains. 250 99

Five human myeloma cell lines, KMM-1, KMS-5, KMS-11, KMS-12-PE, and KMS-12-BM, have been established at Kawasaki Medical School since 1980. As the KMS-12-PE and KMS-12-BM lines were obtained from the same patient, these five cell lines have been derived from four patients with multiple myeloma. The five myeloma cell lines are stably growing at present in RPMI 1640 medium supplemented with 10% fetal bovine serum. They can also grow in a defined culture medium without serum. That these cell lines were human myeloma cells was confirmed by the following findings. Ultrastructurally, all five cell lines showed features characteristic of plasma cells. KMM-1 and KMS-11 cells secreted lambda and kappa chains into the culture medium, respectively, but the other cell lines produced no immunoglobulins. KMM-1 expressed cytoplasmic lambda antigen, KMS-5 showed cytoplasmic delta, and KMS-11 expressed surface kappa, whereas KMS-12-PE and KMS-12-BM cells showed no surface or cytoplasmic immunoglobulins. Regarding reaction with a monoclonal plasma cell antibody (PCA-1), four of the five lines were positive, the exception being KMS-5. Another monoclonal antibody (CD38), which also recognizes plasma cells, responded to KMM-1, KMS-12-PE, and KSM-12-BM. KMS-5 cells expressed acute lymphoblastic leukemia antigens (CALLA). These data suggest that such lines as KMM-1, KMS-11, KMS-12-PE, and KMS-12-BM represent later stages of B-cell differentiation, and that KMS-5 represents a relatively early stage of B-cell differentiation. All the cell lines lacked Epstein-Barr virus nuclear antigen, showed abnormal karyotypes of human origin, and differed from each other in the isozyme patterns examined. Only KMS-5 was tumorigenic when transplanted subcutaneously into nude mice.
 ...
PMID:Establishment of five human myeloma cell lines. 276 32

A myeloma cell line, MM.1, has been established from the peripheral blood cells of a patient with immunoglobulin A myeloma. MM.1 grows in suspension either singly or in small clusters and secretes lambda-light chain. Phenotypically, MM.1 cells lack most B cell antigens, but they do express human leukocyte antigen DR, PCA-1, and T9 and T10 antigens. Molecular analysis of MM.1 demonstrates that it is negative for the presence of the Epstein-Barr virus genome. Southern analysis of MM.1 detected a rearrangement of the lambda-light chain gene, and Northern analysis revealed high levels of lambda gene expression. Cytogenetic analysis of the MM.1 cell line revealed the presence of seven related chromosomally abnormal cell lines characterized by numerical and structural aberrations, and it revealed five nonclonal abnormal cells. The most notable abnormality is a reciprocal translocation involving band q24.3 of chromosome 12 and band q32.3 of chromosome 14; translocations involving 14q32 are frequently observed in neoplasms of B cell origin.
 ...
PMID:Characterization of a novel myeloma cell line, MM.1. 292 41


1 2 Next >>