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)

An inhibition enzyme-linked immunosorbent assay (inhibition-ELISA) was developed for the quantitative determination of human IgG (Gm) allotypes using rabbit anti-Gm antisera, alkaline-phosphatase-conjugated goat anti-rabbit IgG and, as the calibrant, purified human myeloma proteins possessing the relevant Gm allotype. The assay is reproducible and can detect as little as 10 ng/ml of G1m(a), G2m(n) or G3m(st), and 100 ng/ml of G1m(f) or G3m(g). Using this assay, the "gene dosage effect" and "allelic balance" in healthy Japanese were studied.
 ...
PMID:Enzyme linked immunosorbent assay (ELISA) for human IgG (Gm) allotype determination. 201 Nov 29

The native structures of protein phosphatases have not been clearly established. Several tissues contain high molecular weight enzymes which are converted to active species of Mr approximately 35,000 by denaturing treatments or partial proteolysis. We have used a monoclonal antibody directed against purified bovine cardiac Mr = 38,000 protein phosphatase to determine whether this species is the native catalytic subunit or a proteolytic product of a larger polypeptide. Monoclonal antibody was obtained from a cloned hybrid cell line produced by the fusion of Sp2 myeloma cells with spleen cells from a mouse immunized with phosphatase coupled to hemocyanin. This antibody was specific for the Mr = 38,000 phosphatase as determined by immunoblot analysis of purified enzyme or cardiac tissue extracts after native or sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A single immunoreactive protein of Mr = 38,000 was present in cardiac tissue extracts including extracts prepared from freeze-clamped rat heart rapidly denatured in hot sodium dodecyl sulfate buffer. Precipitation of cardiac extract with 80% ethanol did not alter the Mr of the phosphatase nor did it liberate new immunoreactive material not observed in the extract. Ethanol precipitation caused the dissociation of both phosphatase activity and immunoreactivity from a high Mr form to a form of Mr between 30,000 and 40,000. An immunoreactive protein of Mr = 38,000 was identified in several bovine and rat tissues as well as tissues from rabbits, mice and chickens and human HT-29 cells. From these data we conclude that the Mr = 38,000 cardiac phosphatase is a native catalytic subunit of higher molecular complexes which are dissociated by ethanol precipitation. A very similar, or identical, protein is present in several tissues and species suggesting that this catalytic subunit is a ubiquitous enzyme important in many dephosphorylation reactions.
 ...
PMID:Structural characterization of cardiac protein phosphatase with a monoclonal antibody. Evidence that the Mr = 38,000 phosphatase is the catalytic subunit of the native enzyme(s). 299 81

The monoclonal antibody Ki-67, directed against a nuclear antigen expressed by dividing cells in all the phases of cell cycle except G0 and early G1, was used in combination with an anti-BrdU monoclonal antibody, reacting selectively with cells in S-phase, for assessing the percentage of proliferating cells in bone marrow and peripheral blood samples from patients with lymphoma, leukaemia and multiple myeloma. Immunocytochemical labelling of proliferating cells was performed on marrow frozen sections and/or cytospins using an immunoalkaline phosphatase (APAAP) technique that made it possible to obtain proliferative index measurements in a few hours in contrast to the 3-7 d needed with tritiated thymidine. In the 54 marrow lymphoma cases studied a highly significant correlation was observed between the proportion of Ki-67 (+) cells and the separation into low- and high-grade malignant lymphomas according to the Kiel classification. In patients with multiple myeloma at the first diagnosis, the percentage of Ki-67 (+) cells was low (6-10%). In contrast, a high percentage of Ki-67 (+) cells (40-50%) was observed in a young adult with multiple myeloma, in a patient who first presented at the clinical observation with an extradural mass and in three patients who developed extramedullary masses several years after the initial diagnosis of myeloma. In acute lymphoblastic leukaemias of common type the mean value of Ki-67 labelling was 31.3%. Because of their simplicity and rapidity, immunocytochemical techniques may be expected to replace autoradiography and flow cytometry for the detection of proliferating cells in haematological samples.
 ...
PMID:Immunocytochemical evaluation of the percentage of proliferating cells in pathological bone marrow and peripheral blood samples with the Ki-67 and anti-bromo-deoxyuridine monoclonal antibodies. 316 68

An immunoalkaline phosphatase (IAP) technique was used to determine the class of cytoplasmic immunoglobulin presenting in the malignant plasma cells of patients with multiple myeloma. Using monoclonal antibodies against different human immunoglobulins (Igs) as the primary antibodies, and calf intestinal phosphatase as the enzymatic indicator. The presence of monoclonal immunoglobulin was demonstrated within the cytoplasm of malignant plasma cells. These results correlate well with the electrophoretic patterns of the Igs present in the serum samples of these patients. This IAP technique is suggested as a practical method for evaluating the immunophenotype of multiple myeloma.
 ...
PMID:Immunophenotyping of myeloma cells with immunoalkaline phosphatase technique. 381 69

A case of phagocytic, lambda light chain, plasma cell myeloma was characterized by its clinical, morphologic, cytochemical, immunologic, and cell kinetic features. A 40-year-old man presented with Coombs-negative hemolytic anemia, hepatosplenomegaly, lytic bone lesions, lambda light chain monoclonal gammopathy, and infiltration of the bone marrow by dysplastic plasma cells, 10% of which demonstrated phagocytosis of erythroid cells. Electron microscopy demonstrated myeloma cells with prominent cytoplasmic microfilaments and erythroid cells in intracytoplasmic vacuoles. The myeloma cells did not phagocytose staphylococci in vitro. Phagocytic and nonphagocytic myeloma cells were tartrate-sensitive, acid-phosphatase positive, alpha-napthyl butyrate esterase negative, and did not form E rosettes or EAox(IgG) rosettes. The tumor cells were Tdt, Ia antigen, and SIg negative. Immunofluorescent staining for cytoplasmic light chains showed a monoclonal lambda pattern in nonphagocytic myeloma cells, and a probable monoclonal lambda pattern in phagocytic myeloma cells. These findings characterize the neoplasm as a monoclonal proliferation of differentiated plasma cells with the capability of erythrophagocytosis. Erythrophagocytosis by myeloma cells may have been responsible for the hemolytic anemia. The tritiated thymidine labeling index (LI%) was high (8%), suggesting a poor prognosis, despite a dramatic initial response to chemotherapy.
 ...
PMID:Phagocytic, lambda light chain, plasma cell myeloma. 619 Mar 96

Rabbit skeletal muscle protein phosphatases C-I and C-II have been previously isolated as two proteins of Mr = approximately 35,000. Both enzymes display broad substrate specificities but have distinct enzymatic properties in regard to their susceptibility to heat-stable protein inhibitor-2 and their response to divalent cations. Monoclonal antibodies against both protein phosphatase C-I and C-II were produced by fusion of spleen cells of immunized BALB/c mice with SP2/0-Ag14 mouse myeloma cells. The products of the hybrid cells were screened by solid phase radioimmunoassay for the production of antibodies to protein phosphatase C-I and C-II. Positive cells were cloned and injected into mice to produce ascitic fluids. Ten monoclonal antibodies against phosphatase C-I and eight monoclonal antibodies against phosphatase C-II were obtained. These antibodies were characterized with regard to their relative binding affinities to the two protein phosphatases and their abilities to inhibit the phosphorylase phosphatase activities of the two enzymes. All ten of the phosphatase C-I monoclonal antibodies inhibited the phosphorylase phosphatase activity of phosphatase C-I, and three of these also inhibited phosphatase C-II. Only one of the eight antibodies to phosphatase C-II was inhibitory and inhibited the activities of both phosphatase C-I and C-II. Examination of the binding of these monoclonal antibodies by a solid phase radioimmunoassay showed that eight of the ten phosphatase C-I antibodies cross-reacted with phosphatase C-II, while all eight of the phosphatase C-II antibodies cross-reacted with phosphatase C-I. These findings show that phosphatases C-I and C-II possess common antigenic determinant(s) and may, therefore, be structurally related proteins.
 ...
PMID:Monoclonal antibodies to rabbit skeletal muscle protein phosphatases C-I and C-II. 632 26

Staphylococcal neutral phosphatase (NPtase) was purified from two Staphylococcus aureus strains by sequential high salt extraction, ultracentrifugation and ion exchange chromatography. The enzyme showed maximum phosphatase activity at neutral pH, appeared as two bands in SDS-PAGE (31 and 32 kDa), and the isoelectric point was > 10. No close similarity between NPtase and other known bacterial proteins in respect of their N-terminal amino acid sequences was found. Purified NPtase bound rat and human polyclonal IgG [intact and F(ab')2 fragments], IgM, IgA, intact myeloma immunoglobulins, myeloma light chains, gamma heavy chain and, with a much lower affinity, Fc fragments. Furthermore, NPtase can bind serum albumin. Heparin, a highly negatively charged molecule, significantly inhibited NPtase binding to immunoglobulins and HSA, but did not inhibit the binding of specific antibodies to NPtase; this indicates that charge interactions are important. The newly characterized staphylococcal phosphatase with binding properties for immunoglobulin is an interesting bacterial protein that could be involved in post-infectious sequelae.
 ...
PMID:Staphylococcal neutral phosphatase. A highly cationic molecule with binding properties for immunoglobulin. 788 57

The c-cbl proto-oncogene product (p120cbl) forms a stable complex with the Tyk-2 protein tyrosine kinase in various human cell lines of diverse hematopoietic origin. In U-266 myeloma and 293T embryonic kidney cells, p120cbl is rapidly phosphorylated on tyrosine in an IFN alpha-dependent manner. p120cbl also acts as a specific substrate for the Tyk-2-associated SHP-1 phosphatase in vitro, suggesting that this phosphatase plays a regulatory role on the phosphorylation of the protein. These data provide evidence that p120cbl interacts with the functional Type I IFN receptor complex, and suggest its involvement in IFN alpha signaling.
 ...
PMID:Interaction of the c-cbl proto-oncogene product with the Tyk-2 protein tyrosine kinase. 878 Jun 98

Recently, a novel phosphatase designated PTEN/MMAC1/TEP1 and located on chromosome 10q23.3 has been implicated as a new tumor suppressor gene in human cancer. Allelic loss and mutation of this gene has been reported in epithelial derived tumors, including breast cancer and prostate cancer, and in glioblastoma multiforme. The present study was designed to evaluate the potential involvement of PTEN in the pathogenesis of lymphoid neoplasms. We analyzed 27 hematopoietic cell lines (representing a variety of lymphoid lineages), 65 primary lymphoid tumors (including 24 lymphoblastic leukemia/lymphoma [LBL], 30 large B-cell lymphoma [LBCL], 7 Burkitt's lymphoma [BL], and 4 anaplastic large cell lymphoma [ALCL]), and 25 nonmalignant lymph node controls. Gene deletion and gross rearrangement were evaluated using Southern blot analysis, and mutations were studied by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) (PCR-SSCP) and sequencing. Six of 27 cell lines (22.2%) and 3 of 65 primary lymphomas (4.6%) contained alterations of this gene. A large homozygous deletion spanning exons 2 through 5 was detected in one LBL cell line, and two insertions potentially resulting in premature termination, were detected in a second LBL cell line. Nonconservative nucleotide variations were found in two other cell lines (one LBCL and one BL) and in one primary case of LBCL. In addition, two other cell lines (one BL and one myeloma) and two primary lymphomas, both LBCL, contained small deletions within intron 7. These deletions mapped to a poly-T-rich tract just 5' to the intron 7/exon 8 spice site. Their significance is unclear, as they may represent polymorphisms. Overall, our results suggest that abnormalities of the PTEN gene can contribute to pathogenesis in a small percentage of malignant lymphomas.
 ...
PMID:PTEN gene alterations in lymphoid neoplasms. 978 81

Biochemical abnormalities associated with the development of multiple myeloma have been difficult to define especially in terms of demonstrating an in vivo effect of suspected lesions. Herein, we have identified such a defect associated with lack of expression of PTEN, a cellular phosphatase involved in the regulation of phosphatidylinositol phosphates (PIP's). In myeloma cells, PIP's are required for phosphorylation of Akt, a key event leading to inhibition of apoptosis. Loss of PTEN results in a failure to de-phosphorylate PIP's and a corresponding increase in Akt phosphorylation. OPM-2 cells lacking PTEN expression have the highest level of Akt phosphorylation of eight lines examined. Loss of PTEN was found to be associated with a 630 bp deletion corresponding to amino acids 56 - 267. Ectopic expression of wild type PTEN in OPM-2 cells inhibited Akt phosphorylation which was correlated with an increase in apoptosis. The in vivo relevance of loss of PTEN expression was demonstrated by injecting control and wild type PTEN transfected OPM-2 cells into SCID mice. Tumors arose at an incidence of 100% in controls, but only 50% (and of smaller size and longer latency) in low PTEN expressing clones. Importantly, clones expressing high levels of PTEN failed to produce tumors even at five times the latency period of controls. These results demonstrate that PTEN deletion/mutation is responsible for in vivo growth of this tumor and suggests that PTEN regulation may play an important role in tumor development in a subset of multiple myeloma patients. Oncogene (2000) 19, 4091 - 4095
 ...
PMID:Expression of PTEN in PTEN-deficient multiple myeloma cells abolishes tumor growth in vivo. 1096 69


1 2 3 4 5 Next >>