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

Mouse myeloma cells pulse-labeled in vitro with (3)H-leucine or (3)H-glucosamine were fractionated on sucrose gradients, and membrane-bound and free polyribosomes were separated. Nascent polypeptides released from polyribosomes were precipitated with antiserum specific for mouse immunoglobulin. The results indicate that immunoglobulin is synthesized preferentially by bound polyribosomes.
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PMID:Immunoglobulin synthesis and secretion. V. Incorporation of leucine and glucosamine into immunoglobulin on free and bound polyribosomes. 527 48

This study was designed to determine the time in the intracellular life of immunoglobulin when the carbohydrate moieties are added. Plasma cells from a mouse myeloma tumor were exposed to glucosamine-(3)H (a "bridge" sugar), galactose-(3)H, or leucine-(3)H. With each of the above isotopes, the percentage of total radioactive immunoglobulin that has been secreted after different periods of labeling and the extent to which puromycin prevented incorporation into immunoglobulin were determined. The results indicate that both galactose and glucosamine (in its N-acetyl form) become covalently incorporated into immunoglobulin G late in its intracellular life and suggest that glucosamine is also added onto nascent polypeptide chains (i.e., on polyribosomes).
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PMID:Immunoglobulin synthesis and secretion. I. Biosynthetic studies of the addition of the carbohydrate moieties. 545 11

The subcellular sites of synthesis and route of intracellular transfer of immunoglobulin G (IgG) have been investigated by electron microscope radioautography with precursors used for the polypeptide chain (leucine-(3)H) and for the carbohydrate moieties (galactose-(3)H and glucosamine-(3)H). For this purpose, plasma cells from a mouse myeloma tumor were labeled with appropriate precursors and the distribution of radioautographic grains was determined at the end of the labeling period and after varying times of incubation in unlabeled medium. The results indicated that the polypeptide backbone is synthesized in a region of the cell occupied by the rough endoplasmic reticulum (RER) and is transported from there to the region of the Golgi complex. Galactose is incorporated in IgG primarily at the level of the Golgi complex, whereas the incorporation of glucosamine appears to take place both in the RER and in the Golgi complex. From the Golgi complex, the completed IgG molecules reach the plasma membrane and are discharged extracellularly. The latter route of transport and the mechanism of discharge are not understood but may be mediated via smooth-surfaced vesicles.
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PMID:Immunoglobulin synthesis and secretion. II. Radioautographic studies of sites of addition of carbohydrate moieties and intracellular transport. 546 Apr 63

Cells from an established line of Burkitt's lymphoma (Daudi) and a mouse myeloma (P(3)K) were pulse-labeled in vitro with (3)H-leucine, and immunoglobulin was immunologically precipitated from cell lysates and secretions. In contrast to P(3)K cells, Daudi cells synthesize a small amount of Ig which is not secreted. Subcellular fractionation experiments indicated that Ig of Daudi cells is synthesized on membrane-bound polyribosomes and enters the cisternae of the microsomes. Ig in the microsomes could be labeled with either (3)H-galactose or (3)H-fucose suggesting that transport proceeds to the Golgi complex. Additional evidence indicates that Ig molecules are transported to the plasma membrane but are not cleaved from the cell surface. These results together with other studies of Burkitt lymphoma cells suggest that the Daudi line may represent a clone of neoplastic cells derived from normal lymphocytes which synthesize but do not secrete Ig. Similarities between lymphoma cells and antigen-binding cells are discussed.
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PMID:Immunoglobulin synthesis and secretion. VI. Synthesis and intracellular transport of immunoglobulin in nonsecretory lymphoma cells. 554 61

This study delineated the distribution of reactivity of malignant human lymphoid cells with monoclonal antibodies Leu 1 and OKT1, and correlated this expression with that of conventional lymphoid cell markers. The presence of Leu 1 on benign lymph nodal T-cells and its absence from benign lymph nodal B-cells was confirmed. Twenty-two T-cell neoplasms, expressing a variety of intrathymic and mature peripheral phenotypes, expressed Leu 1, but this expression was heterogeneous with respect to percent-positive cells and antigenic density, and appeared to correlate with stages of T-cell differentiation. This study demonstrated the expression of Leu 1 by 33 of 36 cases of B-CLL, by 10 of 15 cases of the closely allied small lymphocytic cell lymphoma, and by 9 of 29 follicular center-cell lymphomas. This included B-cell malignancies of each surface immunoglobulin isotype, and some cases associated with a monoclonal protein spike. Leu 1 was not expressed by myeloma plasma cells, and was absent from non-B, non-T acute lymphoblastic leukemia cells in each of 15 cases studied. Finally, Leu 1 and OKT1 were expressed in parallel, with respect to percent-positive cells and staining intensity, on benign and malignant T-cells, and on malignant B-cells, wherever studied. Possible explanations for this shared antigen are the existence of a minor Leu 1+ B-cell subset, a transformation-associated event, or glycosylation.
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PMID:Reactivity of monoclonal antibodies Leu 1 and OKT1 with malignant human lymphoid cells. Correlation with conventional cell markers. 619 56

We have studied effects of two partially purified human leukocyte (alpha) interferon (IFN) preparations (PIF-A and PIF-B) and a highly purified fibroblast (beta) IFN on the functional activity of normal human neutrophils (PMNs). In vitro, PIF-B conferred a significant and dose-dependent enhancement of chemiluminescence (CL) induced both by phagocytosis and a soluble stimulus, f-Met-Leu-Phe, and decreased killing of Staph. aureus. In contrast, PIF-A caused only a slight inhibition of bactericidal activity and had no effects on CL. beta-IFN had no effects on either bactericidal activity or CL. Migration under agarose was decreased with all of the IFN but phagocytosis and release of enzymes was not affected. PMNs from seven patients treated with PIF-A for multiple myeloma exhibited increased CL responses but no other PMN functions were affected. The findings that human IFN preparations affect PMN functions indicate that high-dose IFN therapy of immunocompromised patients should be carefully evaluated for the possibility of increased infectious complications.
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PMID:Effects of human interferon preparations on neutrophil function. 620 56

The hyalin material in massive cutaneous hyalinosis, a disease characterized by extensive tumorous periodic acid-Schiff-(PAS) positive extracellular cutaneous deposits, has been elucidated by biochemical and immunologic methods. Three major components were found: kappa light chains, a mannose-rich glycoprotein, and type I collagen. Trace amounts of fibrinogen, fibronectin, laminin, IgG, pregnancy-specific glycoprotein, albumin, and keratan sulfate, but not keratin, were also present. The kappa light chains were monoclonal, cryoprecipiting, and more basic than the kappa chains from two myeloma patients. The glycoprotein, which could not be identified as any known glycoprotein, had an apparent molecular weight of 90,000 D. Amino acid analysis showed that glutamic acid, aspartic acid, leucine, and threonine were abundant, whereas hydroxyproline, hydroxylysine, and sulfhydryl amino acids were absent. The carbohydrate content of the protein was approximately 20%. The major monosaccharides were mannose and N-acetylglucosamine. Galactose, N-acetylneuraminic acid and fucose also were present. The third major component of the hyalin material was identified as type I collagen. A humoral immune response to the storage material was found: the patient's serum contained IgM and IgG class antibodies against the mannosylglycoprotein (90 kD glycoprotein) and against type I collagen.
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PMID:Massive cutaneous hyalinosis. Identification of the hyalin material as monoclonal kappa light chains, adhesive 90 kD glycoprotein, and type I collagen. 620 74

In 17 tests in 14 patients with hairy-cell leukaemia (HCL), peripheral blood Leu 2a+ and 3a+ suppressor and helper cells were present in normal mean percentage (3a+ 63 +/- 15%, normal 64 +/- 8%; 2a+ 39 +/- 16%, normal 34 +/- 8%), absolute (3a+ 0.8 +/- 0.4 x 10(9)/1, normal 0.6-1.4 x 10(9)/1; 2a+ 0.5 +/- 0.4 x 10(9)/1, normal 0.2-0.6 x 10(9)/1), and relative (3a+/2a+) (2.2 +/- 1.3, normal 1.9 +/- 0.7) numbers. In all the 9 untreated patients, 3a+ helper cells were normal or increased in percentage numbers, while 2a+ suppressor cells were normal or slightly reduced. It is suggested that these data explain, at least in part, the lack of immuneparesis of HCL as compared with chronic lymphocytic leukaemia (CLL) which is consistently associated with immuneparesis and an excess of Leu 2a+ suppressor cells. In individual splenectomised patients, some variations in Leu 2a+ and 3a+ numbers were observed, and it is suggested that the spleen, known to be important in the natural history of HCL, may have an influence on peripheral T-cell subsets. Although HCL is clearly shown to differ from CLL and myeloma regarding T-cell subset numbers, the fundamental mechanism underlying this difference remains unknown.
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PMID:Monoclonal antibody-defined T-cell subsets in hairy-cell leukaemia. 621 40

The conformation of the hinge region of the human IgG1 immunoglobulin has been investigated by making use of His-224 in the hinge region as a built-in proton nuclear magnetic resonance (NMR) probe. Human myeloma IgG1 (kappa) proteins Ogo and Yot and human polyclonal IgG were used along with their Fab and F(ab')2 fragments for the assignment of the His-224 signals. The titration behavior of His-224 of the intact IgG and the fragments was compared. It was shown that the titration curves for the intact IgG and the F(ab')2 fragments are identical and quite similar to those for the histidine residue in small peptides. By contrast, the Fab fragments give titration curves which are quite different from those for the intact IgG and the F(ab')2 fragments. Conclusions derived may be summarized as follows: (1) in the intact IgG1, the hinge peptide is fully exposed to the solvent and exhibits internal motion which is much more rapid than the Fab segmental motion with respect to Fc: (2) at the loss of the Fc portion of the IgG, the conformation of the hinge peptide in the F(ab')2 fragments remains unchanged; (3) the heavy--heavy interchain interactions involving the two disulfide bridges do not play the primary role in determining the conformation of the hinge region in the intact IgG as well as in the F(ab')2 fragments; (4) the existence of a small stretch of peptide fragment Thr-225--Leu-234 is essential in maintaining the conformation of the hinge region of the intact IgG and the F(ab')2 fragments; (5) in the Fab fragments, as a result of cleavage of a major portion of the hinge peptide, the C-terminal part of the heavy chain including His-224 is partially folded back toward the globular portion of the polypeptide chains; and (6) the hinge peptide in the Fab fragments still retains a degree of flexibility which is similar to that in the intact IgG and the F(ab')2 fragments.
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PMID:Proton nuclear magnetic resonance studies of human immunoglobulins: conformation of the hinge region of the IgG1 immunoglobulin. 625 77

A monoclonal antibody termed B2 Val 7C7, was produced by the fusion of xenoimmune mouse spleen cells with Sp2/0.Ag 14 myeloma cells. This antibody is specific for a polymorphic lymphocyte antigen; it was detected on cells from 138 out of 177 cattle by both 125I-labelled protein A (solid-phase radioimmunoassay, SPRIA) and gold-labelled protein A (immunogold). Its binding was tested on various cell types (peripheral blood lymphocytes, monocytes, polymorphonuclear cells (PMN), thymocytes) from a variety of normal bovine donors. On the one hand, B2 Val 7C7 detects a determinant present on all IgG-bearing lymphocytes, on 20% of the non-IgG-bearing lymphocytes and on the majority of the monocytes. On the other hand, no binding occurs on any PMN or thymocytes. The detected membrane antigen was isolated by immunoprecipitation from an NP 40 extract of 3H-leucine-labelled cells. On SDS-PAGE, it appears to be composed of two sub-units: a 32 000-dalton and a 27 000-dalton chain. These results show that B2 Val 7C7 recognizes an alloantigenic specificity present on an Ia-like antigen.
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PMID:A bovine 'Ia-like' antigen detected by a xenogeneic monoclonal antibody. 658 90


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