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)

This paper reports the initial progress in a research programme to identify and obtain the relative orientations, in solution, of the amino acid residues that constitute the combining site of the myeloma protein MOPC 315. This protein has a molecular mass of 150,000, but enzymic digestion yields the Fv fragment of molecular mass 25,000 which still has the combining site intact, as judged by the affinity for dinitrophenyl haptens. Analysis of the e.s.r. spectra of a series of dinitrophenyl spin labelled haptens has allowed the dimensions, rigidity and polarity profile of the combining site to be determined. The combining site is a cleft of overall dimensions 1.1 nm x 0.9 nm x 0.6 nm which has considerable structural rigidity. One of these spin labels has also been used to perturb the n.m.r. spectrum of the Fv and using difference spectroscopy the 270 MHz proton n.m.r. spectrum of the amino acid residues in and around the combining site has been obtained. This spectrum contains only the equivalent of about 30 aromatic and 21 aliphatic protons. Comparison of this difference spectrum with that obtained using a diamagnetic analogue suggests that any conformational changes on hapten binding are mainly localized to the combining site. By the use of (n.m.r.) difference spectroscopy the protons of the three histidine residues in the Fv are observed to titrate with pH and have pKa values of about 8.1, 6.9 and 6.1. The histidine resonances with pKa values 6.9 and 6.1 alter slightly in the presence of haptens and also appear in the spin label difference spectrum, and must therefore be in or near to the combining site. These are assigned to His 102H and His 97L. The existence of lanthanide binding sites on the Fv, necessary for the mapping studies, has been demonstrated by measurements of Gd III water relaxation rates in Fv solutions and also by the changes in the Fv tryptophan fluorescence on addition of Gd III. At pH 5.5 there is one tight binding site for the lanthanides (KD approximately 80 muM) but in the presence of hapten this is weakened 10-20 fold with a reciprocal effect on the hapten binding. Measurements of the Gd III quenching of the e.s.r. spectrum of a spin labelled hapten bound to Fv indicate that the lanthanide site is ca. 1.5 nm from the nitroxide moiety.
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PMID:Antibody--hapten interactions in solution. 0 18

The antibody response of BALB/c mice to trinitrophenyl (TNP)-levan or TNP-Nocardia water-soluble mitogen (NWSM) includes a small but significant fraction of antibodies which share idiotypes (Id) with the dinitrophenyl (DNP)- and TNP-binding myeloma protein MOPC-460. Active immunization of BALB/c mice with MOPC-460 or passive administration of anti-460-Id antibodies suppresses the 460-Id+ component of the anti-TNP response. By contrast, active immunization of BALB/c with anti-460-Id antibodies or passive administration of BALB/c anti-[anti-460-Id] antibodies leads to an enhanced 460-Id+ component in the anti-TNP antibodies produced in response to TNP-levan or TNP-NWSM. This enhanced 460-Id+ response appears to be a result of the elimination of suppressor T lymphocytes specific for the 460-Id as T lymphocytes from such mice are unable to suppress the in vitro 460-Id+ response to TNP-NWSM whereas normal T cells are suppressive. These results indicate that suppressor cells specific for 460-Id normally regulate the activation of precursors of cells capable of secreting 460-Id+ anti-TNP antibodies.
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PMID:Cellular basis of regulation of expression of idiotype. II. Immunity to anti-MOPC-460 idiotype antibodies increases the level of anti-trinitrophenyl antibodies bearing 460 idiotypes. 8 84

Immunochemical and chemical studies were used to monitor and evaluate the structural changes produced by an enzyme from Turbo cornutus in periodate-oxidized and Smith-degraded, human blood-group substances from ovarian cysts. After the first step of periodate oxidation and Smith degradation, two blood-group substances, JS (HLeb and N-1 (Lea), were precipitated by mouse-myeloma S117 serum, specific for terminal, nonreducing, beta-D-linked 2-acetamido-2-deoxy-D-glucosyl groups, but not by type XIV antipneumococcal horse serum specific for terminal, nonreducing, beta-D-linked D-galactosyl groups. An exoglycosidase, 2-acetamido-2-deoxy-beta-D-hexosidase (beta-N-acetylhexosaminidase) from Turbo cornutus, split off 2-acetamido-2-deoxy-D-glucose amounting to 22.5 and 20.4% of the total weight of JS and N-1 blood-group substances, respectively. After enzymic digestion, both blood-group substances precipitated with type XIV serum, and did not precipitate with S117 serum. The findings are in agreement with the structure propsed for the water-soluble, blood-group substances [Lloyd and Kabat, Proc. Natl. Acad. Sci. U.S.A., 61 (1968) 1477]. Specific enzymes can be of value in structural studies when used in conjunction with sequential periodate oxidation and Smith degradation.
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PMID:Action of 2-acetamido-2-deoxy-beta-D-hexosidase from Turbo cornutus on periodate-oxidized and Smith-degraded, blood-group HLeb and Lea substances from human, ovarian-cyst fluids. 21 37

Small unilamellar lipid vesicles bearing the DNP-hapten on their surfaces and containing the water-soluble fluorescent dye carboxyfluorescein were formed by sonication. These vesicles were incubated with cells from the murine myeloma tumor MOPC 315, which secrete and also bear on the cell surface an immunoglobulin with affinity for the nitrophenyl hapten. At 0 degrees C the cells bound an average of several thousand vesicles at saturation. This binding was specific for the nitrophenyl hapten on the vesicle since it was abolished by an excess of soluble nitrophenyl derivative, by omission of the hapten from the vesicle, or by substitution for MOPC 315 of a tumor lacking receptors for the nitrophenyl hapten. Specific binding of vesicles was greater when cells were incubated at 37 degrees C. The study suggests that ligand-bearing vesicles can be a useful marker for cell surface immunoglobulin. However, in spite of the ability to "target" vesicles to cell surface determinants, binding did not result in increased delivery of vesicle contents to the cytoplasm.
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PMID:Binding of antigen-bearing fluorescent liposomes to the murine myeloma tumor MOPC 315. 36 42

Man and terrestrial animals live in an environment containing free-living amoebae on the surface soil, in pools, fresh water lakes, rivers and streams. They form cysts, which float in the air and which are continually inhaled and found in the nasopharynx and their trophozoites are present in human and animal faeces. Amoebae of the genus, Naegleria, have been demonstrate; in all human tissues, both healthy and in larger numbers in those taken from cases of rheumatoid disease, in all human cancers and in the unaffected tissues of cancer patients. They can be killed in vitro by a series of different anti-amoebic substances and treatment of active cases of rheumatoid disease by any of these, either causes cessation of disease activity or a temporary exaggeration of symptoms followed by their lessening or disappearance (Herxheimer reaction), indicating the presence of an amoeba in the affected tissues as the causative organism of the inflammation in this disease in subjects genetically sensitive to the organism. Every internal organ may be involved in the inflammatory response in cases of rheumatoid disease and this also ceases with the above treatments. Many of these internal lesions are premalignant, so that infection with the organism either in sensitive subjects or with pathogenic species, appears to be the primary cause of cancer in many cases. The presence in the body of Naegleria represents the source of the constant antigenic stimulation thought to be responsible both for rheumatoid disease and for the development of lymphomata and myelomatosis.
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PMID:The naeglerial causation of rheumatoid disease and many human cancers. A new concept in medicine. 53 42

Longitudinal and transverse proton relaxation rates for water in the hydration spheres of Gd(III) bound to the non-immune rabbit IgG fragments Fc (C-terminal half of heavy-chain dimer), pFc' (C-terminal quarter of heavy-chain dimer) and Fab (N-terminal half of heavy and light chain) have been measured at a number of frequencies and temperatures using pulsed nuclear magnetic resonance spectrometry. For the fragments Fc and pFc', a full computer analysis showed that the results could be fitted by parameters of similar magnitude to those found previously for IgG. In contrast to the results for the other complexes the Fab -Gd(III) complex showed no slow exchange contribution to the relaxation rates. Under these circumstances it was found possible to obtain an accurate value for the hydration number (q) from measurements of the longitudinal and transverse relaxation rates at a chosen frequency such that the product of the nuclear Larmor frequency (omega1) and the correlation time for the dipolar relaxation processes (tauc) was approximately unity. Water-proton relaxation rates were also determined for the complex of Gd(III) with the Fv fragment of the mouse myeloma protein MOPC 315. A computer analysis of the results revealed a slow exchange contribution to the rates and this gave errors in the variable parameters similar to those observed previously for IgG, Fc and pFc'. The conclusions drawn from the different systems are discussed in terms of the present state of application of the proton relaxation enhancement technique in biology.
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PMID:The determination of molecular-motion parameters from proton-relaxation-enhancement measurements in a number of Gd(III) - antibody-fragment complexes. A comparative study. 56 Feb 99

Till present the advantages of methacrylate embedded bone biopsies for the diagnosis of haemoblastic disorders have been somewhat restricted. This was a result of the impossibility to apply histochemical methods and other sensitive staining procedures to semithin sections. A routine method is described whereby enzyme activity, excellent fixation and good sectioning ability are retained. Fixation is carried out using 4% purified formaldehyde buffered in 0.1M sodium cacodylate. Dehydration is done with a water-miscible glycolmethacrylate. Naphthol-AS-D-chloroacetate esterase activity can be observed in granules of the entire neutropil cell lineage. By use of this method it becomes possible to demonstrate acid phosphatase activity and immunoglobulins in atypical plasma cells of multiple myeloma. A considerable decrease in processing time, as well as a preservation of enzyme activity during the postal mailing of fixed tissue samples from outside are further advantages.
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PMID:Histochemical and immunohistochemical techniques on acrylate embedded bone biopsies. 76 58

The Sia test was performed in strictly standardized conditions in boiled, bidistilled, deionized water (BBD) and in 0.01 M phosphate buffers pH 5.0 and 7.0. Normal human sera and sera from patients with diffuse hypergammaglobulinemia ( greater than 2.0 g/100 ml), immunoglobulin G (IgG) myeloma (M component greater than 5.0 g/100 ml), and Waldenstrom's macroglobulinemia were studied. In BBD all normal sera were Sia-negative, whereas 16 per cent of sera with diffuse hypergammaglobulinemia, 60 per cent of sera with IgG M component, and 44 per cent of macroglobulinemic sera with Sia-positive. Almost all sera from the above mentioned four groups gave positive results in phosphate buffer pH 5.0 and the majority of them, with the exception of normal human sera, gave positive results at pH 7.0. All precipitates isolated from the sera tested showed beta-alpha 2 bands in cellulose acetate electropherograms. Precipitates from the sera with diffuse hypergammaglobulinemia also showed gamma bands, and those from the myelomatous or macroglobulinemic sera showed strong bands corresponding to the M components. Whereas immunoelectrophoresis of the four-fold-concentrated precipitates showed up to 11 precipitation lines, radial immunodiffusion detected up to 18 proteins. The characteristic pattern of IgM/IgG immune complexes was observed in immunoelectrophoresis of Sia precipitates from hypergammaglobulinemic sera with rheumatoid factor. The recovery of immunoglobulins in the Sia precipitates varied greatly but that of IgM was usually greater than that of IgG or IgA. It may be concluded that the Sia test is entirely nonspecific regardless of the buffer or pH at which it is performed. The only advantages of this test seem to be the quick partial purification of IgM components and identification of their light chains, and the possible detection of immune complexes.
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PMID:Immunochemical and physical studies of the Sia test. 81 99

A method for obtaining luminescent sera, consisting in isolation of pure antigens G, A, M from human gamma-globulin and blood serum from patients with myeloma disease is suggested. A native antiserum was obtained by immunization of rabbits with water-insoluble polycondensate of antigens "sewn" with glutaric aldehyde. Adsorption of antisera as well as specific antigens was carried out with antigen- and antibodyimmunosorbent, the latter being obtained with the help of both glutaric aldehyde and sefarose 4B treated with cyanogen bromide. The sera had a specific titre in the precipitation reaction against their own antigens 1:32 and were highly specific. A globulin fraction was obtained by sedimentation with polyethylene-glycol. Marking of the specific protein with fluoresceine isothiocyanate was carried out using the dialysis method with subsequent purification on sefadex and DEAE-cellulose. The application of the abovementioned sera made it possible to ascertain the character of distribution of deposits of immunoglobulins in glomeruli in systemic lupus erythematodes, glomerulonephritis and in the cells of the synovial fluid sediment in rhematoid arthritis.
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PMID:[Utilization of luminescent monospecific sera against human immunoglobulins G, A and M for diagnostic purposes]. 110 50

Campylobacter rectus is one of the predominant bacteria in the lesions of human periodontitis. The surface antigens of the bacterium contain several components which may play significant roles in colonization and pathogenesis. A high-molecular-weight protein was selectively isolated from the cell surface of C. rectus by acid extraction and purified by DEAE Sepharose. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that the extracted protein was 150 kDa. The protein was not found in Campylobacter curvus ATCC 35224 or Wolinella succinogenes ATCC 29543. Lipopolysaccharide (LPS) was extracted from various C. rectus strains by the hot phenol-water method. SDS-PAGE patterns revealed that C. rectus LPS was the smooth type in nature. Monoclonal antibodies against C. rectus were generated by the fusion of SP2/0 myeloma cells with splenocytes from BALB/c mice immunized with whole cells of C. rectus ATCC 33238 strain. An Immunoglobulin G1 monoclonal antibody reacted with the high-molecular-weight proteins from 4 of 9 C. rectus strains, indicating that the 150 kDa protein exhibits antigenic heterogeneity. Immunoelectron microscopic study revealed that the monoclonal antibody recognized the S-layer of C. rectus cells. An IgM monoclonal antibody reacted with LPSs from C. rectus strains at molecular weights between approximately 20.0 kDa and 24.0 kDa. The monoclonal antibody did not react with any other LPSs from C. curvus ATCC 35224 or W. succinogenes ATCC 29543. The reactivities of this monoclonal antibody indicate that it recognizes an O-specific side chain epitope of C. rectus LPS. Sera from patients with adult periodontitis showed strong reactivity with the 150 kDa protein antigen and LPS from C. rectus strains. As determined by immunoblotting analysis, sera from periodontally healthy individuals, however, showed little or no reactivity. The levels of serum IgG antibodies of patients with periodontitis to the protein antigen and LPS were statistically significantly higher than those of periodontally healthy individuals, as assessed by an enzyme-linked immunosorbent assay.
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PMID:Analysis of cell surface antigens of Campylobacter rectus. 130 24


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