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 study characterized the N-glycans of a humanized immunoglobulin G4 (IgG4) expressed in NS/O mouse myeloma cells and directed against the CD18 family of adhesion-promoting receptors on leukocytes. The N-glycans were released from the purified recombinant IgG by N-glycanase treatment, purified by Sephadex G50 chromatography, and fractionated by Bio-Gel P-4 chromatography into three oligosaccharide pools. Each pool was analyzed individually by glycosyl composition analysis, high-pH anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD), 600-MHz 1H-NMR spectroscopy, and electrospray-ionization mass spectrometry. In addition, each of the three pools was subfractionated by HPAEC and the isolated subfractions that contained sufficient material were hydrolyzed and analyzed for glycosyl composition by HPAEC-PAD. The overall results indicate the presence of five oligomannoside-type structures (containing 5 to 8 Man residues) which are not usually found in IgG, and the presence of eight diantennary (mostly truncated) N-acetyllactosamine-type structures which are typical of mouse and human IgGs. The N-acetyllactosamine-type structures were heterogeneous with regard to alpha(1-->6) fucosylation of the linkage GlcNAc, and the presence or absence of GlcNAc and/or Gal beta(1-->4)GlcNAc extending the core pentasaccharide (Man3GlcNAc2). No evidence was found for the presence of sialic acid or bisecting GlcNAc residues on the N-acetyllactosamine-type chains. The latter finding suggests that the N-glycans of this humanized IgG are of the mouse type.
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PMID:Structural characterization of the N-glycans of a humanized anti-CD18 murine immunoglobulin G. 790 4

The appearance of high resolution neutral lipid signals in the 1H NMR spectra of myeloma cells grown in the presence of oleate was shown to correlate with the appearance of cytoplasmic lipid droplets observable by electron microscopy. The spin-spin relaxation times of these lipid signals were similar to those measured previously for lipid resonances in other cell types. These data suggest that cytoplasmic lipid droplets could make a significant contribution to the neutral lipid signals observed in the 1H NMR spectra of some cells.
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PMID:The appearance of neutral lipid signals in the 1H NMR spectra of a myeloma cell line correlates with the induced formation of cytoplasmic lipid droplets. 846 71

31P NMR spectra were obtained from sera of 22 healthy volunteers and 20 patients with multiple myeloma at the time of diagnosis and repeated up to five times during therapy. All spectra consisted of a Pi peak (used as a reference peak) and two peaks from phospholipids (PL): one peak due to phosphatidylethanolamine and sphingomyelin (PE + SM) and a second peak due to phosphatidylcholine (PC). Prior to therapy, peak intensities of the phospholipids were low relative to Pi. During therapy leading to remission, the resonance from PL progressively increased to approximate the spectral pattern seen in normal sera. By contrast, in non-responders an opposite trend was noted: the intensities of the phospholipid peaks became progressively reduced or remained unchanged. Long-term follow-up studies showed a good correlation between this 31P MRS evaluation of sera and the response of the disease to the therapy. In addition to the correlation with tumor response, our studies also show significant correlations between area, intensities of peaks of PE + SM, PC, and the concentrations of high-density lipoprotein (HDL) (correlation coefficients 0.46, 0.43, 0.59, respectively; p < 0.001). We found that the concentration of HDL in serum of patients with multiple myeloma was significantly reduced. In individuals responding to therapy HDL levels increased to the point where there were no statistically significant differences between them and healthy volunteers. In patients not responding to therapy, HDL concentration did not increase.(ABSTRACT TRUNCATED AT 250 WORDS)
NMR Biomed 1995 May
PMID:Chemotherapy-associated changes in 31P MRS spectra of sera from patients with multiple myeloma. 858

Interleukin-6 (IL-6) is a multifunctional cytokine which is involved in a broad spectrum of activities such as immune defense, hematopoiesis, and the acute phase response, as well as in the pathogenesis of multiple myeloma. A series of murine IL-6 (mIL-6) mutants, H31A, W34A, and H31A/W34A, were constructed to investigate the roles of His31 and Trp34 in the structure, conformational stability, time-dependent aggregation, folding, and spectral properties of mIL-6. The characteristic pH-dependent quenching of fluorescence of mIL-6 at low pH was shown to be caused by an interaction between Trp34 and protonated His31 at low pH and not associated with Trp157. Denaturant-induced equilibrium unfolding experiments monitored by fluorescence and far-UV CD showed that the increased quantum yield and blue shift of the wavelength of the emission maximum observed for mIL-6 at moderate denaturant concentrations were also associated with Trp34, rather than Trp157. The tendency to form aggregation-prone unfolding intermediates, as judged by poor fits to a two-state unfolding mechanism, low m values (slopes of the unfolding curve in the transition region), and the range of denaturant concentrations over which these intermediates formed, was shown to be higher for H31A than mIL-6 but significantly lower for W34A and H31A/W34A. These differences were most pronounced at pH 7.4 and correlated with the tendencies of the proteins to aggregate at high protein concentrations in the absence of denaturant. As judged by the 1H NMR chemical shifts of the aromatic residues, the global conformations of H31A and W34A were not significantly different from that of mIL-6. Nuclear Overhauser effects (NOE) between the side chains of His31 and Trp34 were consistent with the indole side chain of Trp34 being oriented toward the face of the imidazolium side chain of His31, an arrangement consistent with our estimates of a low interaction energy (0.4-0.6 kcal/mol) between these side chains. A shift in the pKa of the His31 side chain in W34A (+0.3 unit) suggested that, in the absence of Trp34, His31 could interact with other residues. Further mutations in this region should yield forms of mIL-6, even less prone to aggregation, which would be more suitable for NMR studies. Mutation of His31 and Trp34 to alanine did not significantly alter the mitogenic activity of the mutants on mouse hybridoma 7TD1 cells, even though the corresponding region of human IL-6 has been shown to be important for biological activity.
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PMID:Roles of histidine 31 and tryptophan 34 in the structure, self-association, and folding of murine interleukin-6. 916 91

In order to study 2'-deoxycytidine (2'-dCyd) as a possible prognostic marker in cancer chemotherapy, an enzyme immunoassay (EIA) was developed. 2'-dCyd as a hapten was succinylated and two omicron-monosuccinyl-2'-dCyd's were purified by high performance liquid chromatography and identified by mass spectrometry and 1H-NMR. Two antigens were prepared by conjugating two omicron-succinyl derivatives with keyhole limpet hemocyanin (KLH) as a carrier. Both antigen produced specific antibodies to 2'dCyd in BALD/c mice. The spleen cells of one mouse immunized with 5'-omicron-succinyl-2'-dCyd-KLH were hybridized with myeloma cells. One monoclone selected produced a specific antibody. A convenient EIA was attained by using the monoclonal antibody.
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PMID:Development of enzyme immunoassay of 2'-deoxycytidine. 922 50

The occurrence of the alpha2-->8-linked oligomeric form of N-glycolylneuraminic acid (oligo-Neu5Gc) residues in mammalian glycoproteins was unequivocally demonstrated using a newly developed anti-oligo/poly-Neu5Gc monoclonal antibody as well as by chemical and biochemical methods. First, the antibody, designated mAb.2-4B, which specifically recognized oligo/poly-Neu5Gc with a degree of polymerization of >2, was developed by establishing a hybridoma cell line from P3U1 myeloma cells fused with splenocytes from an MRL autoimmune mouse immunized with dipalmitoylphosphatidylethanolamine-conjugated oligo/poly-Neu5Gc. Second, oligo-Neu5Gc was shown to occur in glycoproteins derived from pig spleen by Western blot analysis using mAb.2-4B, which was also confirmed by fluorometric high performance liquid chromatographic analysis of the product of periodate oxidation/reduction/acid hydrolysis of the purified glycopeptide fractions and by TLC and 600-MHz 1H NMR spectroscopic analysis of their mild acid hydrolysates. Finally, the ubiquitous occurrence of oligo-Neu5Gc chains as glycoproteinaceous components in Wistar rat tissue was immunochemically indicated. This is the first example demonstrating the diversity in oligo/poly-Sia structure in mammalian glycoproteins, where only poly-N-acetylneuraminic acid is known to occur. Such diversity in oligo/poly-Sia structure also implicates a diverged array of biological functions of this glycan unit in glycoproteins.
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PMID:Identification of oligo-N-glycolylneuraminic acid residues in mammal-derived glycoproteins by a newly developed immunochemical reagent and biochemical methods. 944 59

The glutamine metabolism was studied in glucose-starved and glucose-sufficient hybridoma and Sp2/0-Ag14 myeloma cells. Glucose starvation was attained by cultivating the hybridoma cells with fructose instead of glucose, and the myeloma cells with a low initial glucose concentration which was rapidly exhausted. Glutamine used in the experiments was labeled with 15N, either in the amine or in the amide position. The fate of the label was monitored by 1H/15N NMR analysis of released 15NH+4 and 15N-alanine. Thus, NH+4 formed via glutaminase (GLNase) could be distinguished from NH+4 formed via glutamate dehydrogenase (GDH). In the glucose-sufficient cells a small but measurable amount of 15NH+4 released by GDH could be detected in both cell lines (0.75 and 0.31 micromole/10(6) cells for hybridoma and myeloma cells, respectively). The uptake of glutamine and the total production of NH+4 was significantly increased in both fructose-grown hybridoma and glucose-starved myeloma cells, as compared to the glucose-sufficient cells. The increased NH+4 production was due to an increased throughput via GLNase (1.6 -1.9-fold in the hybridoma, and 2.7-fold in the myeloma cell line) and an even further increased metabolism via GDH (4.8-7.9-fold in the hybridoma cells, and 3.1-fold in the myeloma cells). The data indicate that both GLNase and GDH are down-regulated when glucose is in excess, but up-regulated in glucose-starved cells. It was calculated that the maximum potential ATP production from glutamine could increase by 35-40 % in the fructose-grown hybridoma cells, mainly due to the increased metabolism via GDH.
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PMID:Elevated glutamate dehydrogenase flux in glucose-deprived hybridoma and myeloma cells: evidence from 1H/15N NMR. 1009 57

Staging and monitoring of multiple myeloma (MM) is mainly based on monoclonal component quantification; the absence of such a parameter renders difficult follow up of patients with nonsecretory MM (nsMM). In this study our aims were to determine the specificity and sensitivity of Tc99m-sestaMIBI scintigraphy at diagnosis and during follow up of nsMM patients. Nine nsMM patients were prospectively studied at diagnosis and during treatment for a mean time of 33 months (range: 12-65+). Tc99m-sestaMIBI (MIBI) scintigraphy was compared to conventional imaging (CI: X ray with CAT or NMR details) at diagnosis and during follow up. At diagnosis, CI and MIBI were concordant in three patients; CI showed more focal lesions than MIBI in four patients, while MIBI revealed more focal lesions than CI in two patients. During the follow up, MIBI uptake was normal in the four patients who achieved remission. Five patients did not achieve remission: CI and MIBI were concordant in three, while MIBI was falsely negative in two patients. In conclusion, Tc99m-sestaMIBI scintigraphy has high sensitivity (no false positive cases) and 78% specificity (2/9 false negative cases) in tracing active nsMM lesions; it should be considered complementary to CI for monitoring this rare disease.
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PMID:Tc99m-sestaMIBI uptake in nonsecretory multiple myeloma. 1608 47

A novel fluorescent probe 3-perylene diphenylphosphine (3-PeDPP) was synthesized for the direct analysis of lipid hydroperoxides. The structure of 3-PeDPP was identified by the spectroscopic data, FAB-MS, (1)H NMR, and (13)C NMR. The reactivities of 3-PeDPP with lipid hydroperoxides were investigated in chloroform/MeOH homogeneous solutions and PC liposome model systems oxidized by either 2,2'-azobis(2-amidinopropane)dihydrochloride and photosensitized oxidation. The fluorescence intensity derived from 3-perylene diphenylphosphineoxide (3-PeDPPO) increased proportionally with amount of hydroperoxides produced in homogeneous solutions and liposome model systems. 3-PeDPP was easily incorporated into mouse myeloma SP2 cells and thin tissue section for dynamic membrane lipid peroxidation studies. Linear correlations between fluorescence intensity and amount of hydroperoxides in the cell membrane and tissue sections were obtained. The fluorescence intensity from 2-dimensional image analysis was also well correlated with lipid hydroperoxide level in these models. Thus, the novel probe 3-PeDPP is useful for the direct determination of lipid hydroperoxides in biological materials.
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PMID:Development of novel fluorescent probe 3-perylene diphenylphosphine for determination of lipid hydroperoxide with fluorescent image analysis. 1625 45

Two monoterpene glycosides, conjugated with gallic acid [globulusin A (1) and B (2)], together with four known compounds, cypellocarpin A (3), eucaglobulin (4), cuniloside (5) and (1S, 2S, 4R)-trans-2-hydroxy-1,8-cineole beta-d-glucopyranoside (6), were isolated from hot-water extracts of the leaves of Eucalyptus globulus. The structures of compounds 1 and 2 were determined by 1D, 2D NMR and MS spectroscopic analyses. The absolute stereochemistry of 1 was determined by correlating the spectroscopic data with those of synthetic compound 6 with a known configuration. Globulusin A (1) and B (2), cypellocarpin A (3) and eucaglobulin (4), scavenged DPPH free radicals and globulusin A (1) showed a higher antioxidant activity than the other tested compounds, with an IC50 of 3.8microM. Globulusin A (1) and eucaglobulin (4) concentration-dependently suppressed inflammatory cytokine production, tumor-necrosis factor-alpha and interleukin-1beta in cultured human myeloma THP-1 cells co-stimulated with phorbol myristate acetate. These compounds also inhibited melanogenesis in cultured murine melanoma B16F1 cells, without any significant cytotoxicity. These results suggested that globulusin A (1) and eucaglobulin (4), which were isolated as antioxidants from E. globulus, also had anti-inflammatory as well as anti-melanogenesis activity.
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PMID:Bioactive monoterpene glycosides conjugated with gallic acid from the leaves of Eucalyptus globulus. 1793 65


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