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)

The bioconversion of 5-aminolevulinic acid (ALA) into hydrophobic protoporphyrin IX and other water-soluble porphyrins was investigated in Ehrlich ascite carcinoma (EAC) cells and in a myeloma cell line. The effects of irradiation (514 nm), temperature, incubation time and added glucose on the relative porphyrin concentrations (protoporphyrin vs. water-soluble porphyrins) were examined. Variations in these parameters induced a change in the amount of water-soluble porphyrins relative to protoporphyrin IX. The main component of the hydrophilic porphyrins was found to be uroporphyrin (Up), with minor components of coproporphyrin (Cp) and other carboxyporphyrins. The enhanced production of water-soluble porphyrins appears to be associated with alterations in the activities of the various enzymes in the heme biosynthetic pathway, resulting, for example, in the reduction in the activity of mitochondrial enzymes.
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PMID:Formation of water-soluble porphyrins and protoporphyrin IX in 5-aminolevulinic-acid-incubated carcinoma cells. 868 98

Murine monoclonal antibodies (Mabs) against water-soluble somatic antigens (WSSA) and the wall fraction (WF) from Rhizopus arrhizus (Rhizopus oryzae) were produced in vitro by fusion of splenocytes from immunized BALB/c mice with mouse myeloma X63-Ag 8.653 cells. Supernatants reacting only with homologous antigens in an enzyme-linked immunosorbent assay were subsequently screened for reactivity with homologous fungi in immunohistochemical techniques. All four Mabs raised against the WF of A. arrhizus failed to react on tissues. However, four of the Mabs raised against the WSSA of R. arrhizus (Mab-WSSA-RA-1 through Mab-WSSA-RA-4) revealed a high homologous reactivity on tissues and the cross-reactivity of these were subsequently evaluated on tissues containing other members of the family Mucoraceae and other unrelated fungi. On tissues and on immunoblots all four Mabs reacted identically and specifically with members of the family Mucoraceae, i.e., Absidia corymbifera, R. arrhizus, and Rhizomucor pusillus. The Mabs were all isotyped as IgM antibodies, were nonprecipitating, and reacted with homologous antigens with molecular masses from I4 to 110 kDa. With WSSA from A. corymbifera and R. pusillus the four Mabs were bound to antigens from 14 to 52 kDa and from 20 to 28 kDa, respectively. The diagnosis of 145 bovine lesions obtained by one of the specific Mabs (Mab-WSSA-RA-1) were compared to results obtained by heterologously absorbed polyclonal antibodies. In most lesions (n = 140 [approximately 97%]) the Mab and the polyclonal antibodies reacted in a similar pattern, i.e., positively for zygomycosis in 89 lesions, negatively in 41 aspergillosis lesions, and negatively in 10 undiagnosed lesions. Hyphae within two of four lesions in lymph nodes, which were not stained by the polyclonal antibodies, reacted with the specific Mab. However, in another three lesions of lymph nodes stained by the polyclonal antibodies no reactivity was seen with the Mab-WSSA-RA-1. The immunoreactivity of the Mabs (Mab-WSSA-RA-1 through Mab-WSSA-RA-4) raised against WSSA of R. arrhizus justify their application for the in situ diagnosis of systemic bovine zygomycosis.
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PMID:Immunohistochemical diagnosis of systemic bovine zygomycosis by murine monoclonal antibodies. 880 11

Multiple myeloma (MM) is a B-cell neoplasm of unknown etiology. We searched for etiological clues by examining the literature on geographic clusters of MM. We searched the MEDLINE database from 1966 to 1996 for spatial occurrences of MM that were significantly greater than expected (spatial "clusters"). Eight clusters with verified diagnoses of MM were identified. All of the eight clusters occurred in locations that were proximate to a body of water. Six of these bodies of water are known to have been contaminated with dioxins. We hypothesize that the observed association between MM and proximity to bodies of water is caused by exposure to dioxins in individuals who consume local fish and seafood. This hypothesis is consistent with the significantly elevated risks for MM in groups with high consumption of dioxin-contaminated fish, e.g., Baltic Sea fishermen and Alaskan Indians, and among persons accidentally exposed to dioxins in Seveso, Italy. Dioxins are immunotoxic and inhibit the differentiation of B cells. Thus, dioxins are plausible myelomagens. A dioxin hypothesis could illuminate many epidemiological features of MM and may suggest new avenues for analytic research.
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PMID:Multiple myeloma: clusters, clues, and dioxins. 933 70

Murine monoclonal antibodies (MAbs) against water-soluble somatic antigens (WSSA) and the wall fraction (WF) from Aspergillus fumigatus were produced by fusion of splenocytes from immunized BALB/c mice with mouse myeloma X63-Ag 8.653 cells. The supernatants of in vitro cultured hybridomas were initially screened for reactivity with the WSSA and the WF from A. fumigatus and WSSA of other fungi in an enzyme-linked immunosorbent assay (ELISA). Supernatants reacting only with A. fumigatus antigens were subsequently screened for homologous and heterologous reactivity with immunohistochemical techniques using formalin-fixed, paraffin-embedded tissues from experimentally infected mice. Because of a high immunohistochemical reactivity with homologous fungi, 4 MAbs raised against A. fumigatus WSSA and WF were selected for a further evaluation of cross-reactivity (diagnostic specificity) in immunohistochemical and immunoblotting assays. In immunohistochemical assays, all MAbs raised against WSSA cross-reacted heavily with a number of other fungal species. All 4 MAbs (MAb-WF-AF-1-4) raised against the WF reacted strongly with hyphae of Aspergillus spp.; hyphae of Scedosporium apiospermum were also strongly labeled by MAb-WF-AF-3 and -4. The 2 specifically reacting MAbs (MAb-WF-AF-1 and -2) were of the IgM biotype and were precipitating, and in immunoblotting experiments both bound to a 106-kD antigen of the WF, whereas they did not bind to WSSA of A. fumigatus. One of the 2 aspergillosis-specific MAbs (MAb-WF-AF-1) was used to screen 145 mycotic lesions of cattle. The diagnoses on bovine lesions obtained by MAb-WF-AF-1 were compared with results based on reactivity with heterologously absorbed polyclonal antibodies and, for some lesions, to culture results. In the vast majority of lesions (n = 133), the MAb-WF-AF-1 and the polyclonal anti-Aspergillus antibodies reacted in a similar pattern, i.e., positively in 41 aspergillosis lesions and negatively in 92 zygomycotic lesions. Hyphae in 3 of 12 lesions that were not stained by the polyclonal antibodies reacted with the specific MAb-WF-AF-1; i.e., aspergillosis was diagnosed. The characteristics of the 2 MAbs (MAb-WF-AF-1 and -2) raised against the WF of A. fumigatus in ELISA and immunoblotting and immunohistochemical assays justify their application for the in situ diagnosis of systemic aspergillosis of cattle.
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PMID:Development of murine monoclonal antibodies for the immunohistochemical diagnosis of systemic bovine aspergillosis. 902 84

The binding of an immunoglobulin lambda light chain (IgLC) to synthetic and biological membranes was monitored in real-time using a recently developed, time-resolved fluorescence technique. Lambda IgLC purified from the urine of patients with multiple myeloma, were used in studies of protein-membrane interactions. The association of the lambda IgLC dimer with B-lymphocytes was shown to be stabilised predominantly by non-polar interactions. Furthermore, it was found that following binding to synthetic phospholipid membranes, a reorientation of the light chain occurred which resulted in a change in the distribution of charged residues at the lipid-water interface. The rate constants associated with the binding event were calculated, and appear to comprise both temperature insensitive and sensitive components. The calculated activation energies of the binding and reorientation events were found to be 13.53 KJmol(-1) and 87.89 KJmol(-1), respectively. The large activation energy associated with the reorientation phase suggests the movement of large protein domains, possibly involving a whole immunoglobulin domain. The binding and reorganisation of the IgLC upon the phospholipid membrane may confer novel biological functions to the bound protein and potentially contribute to such phenomenon as myeloma-associated immuno-suppression.
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PMID:A study of the interactions of an immunoglobulin light chain with artificial and B-lymphocyte membranes. 915 94

The authors conducted a proportional mortality study of 1,043 deaths that occurred between 1956 and 1992 among men who used mainly dichloro-diphenyl-trichloroethane (DDT) in an anti-malarial campaign in Sardinia, Italy, during the late 1940s. For each cause of interest, investigators compared observed deaths with expected deaths. The estimated DDT exposure ranged from 170 to 600 mg/m3 in indoor operations and from 24 to 86 mg/m3 in outdoor operations. Workers directly exposed to DDT had a significant increase in risk for liver and biliary tract cancers (PMR = 228; 95% confidence interval = 143, 345) and multiple myeloma (PMR = 341; 95% confidence interval = 110, 795). However, the PMR for liver and biliary tract cancers was also elevated among workers who did not have direct occupational contact with DDT, and the authors observed no increase in either PMR, by number of days in exposed jobs. Perhaps DDT did not increase the risk or perhaps occupational exposure, although quite high, did not further increase the risk, compared with the heavy baseline exposure of the entire Sardinian population, (i.e., mainly through diet and drinking water). Expansion of the cohort to include all exposed workers, and collection of information to improve exposure assessment are needed to clarify these findings.
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PMID:Proportional mortality of dichloro-diphenyl-trichloroethane (DDT) workers: a preliminary report. 921 Jul 31

Bacteremia caused by Plesiomonas shigelloides is a rare event, often associated with consumption of seafood and fresh or estuarine water in temperate or tropical climates. Most patients have showed underlying health disorders. Here we present a case of P. shigelloides septicaemia and cellulitis of the left hand associated with fish handling in Northern Sweden (65 degrees latitude north). The patient, who suffered from multiple myeloma, recovered uneventfully after initial treatment with intravenous cefuroxime followed by a course of oral ciprofloxacin. P. shigelloides seems to be ubiquitous in freshwater world-wide and may cause invasive infections also in cold climate areas.
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PMID:A case of Plesiomonas shigelloides cellulitis and bacteraemia from northern Europe. 957 48

Dietary manipulations to prevent cancer and other diseases of aging have drawn broad public and scientific attention. One indicator of this interest is that dehydroepiandrosterone (DHEA) supplements are widely consumed by those who hope that this hormone may keep them "younger longer." However, key data to support this belief are lacking. For example, the influence of DHEA treatment on spontaneous cancer and life span in healthy, long-lived strains of mice or rats is unknown. This is in contrast to the situation for caloric restriction (CR), which is known to oppose cancer development and increase maximum life span in rodents. To address this issue, we assigned 300 middle age (12-month-old) male C57BL/6 mice to one of four groups (n = 75 for each group) and evaluated them for longevity and spontaneous disease patterns. Two groups were fed a normal diet (ND), and two others were fed a calorie-restricted diet (RD). One ND group and one RD group were also given 25 microg/ml DHEA sulfate (DHEAS) in their drinking water. Although urine samples from DHEAS-treated mice contained 10-fold more DHEA and DHEAS than did samples from unsupplemented mice, DHEAS administration did not affect body weight, life span, or cancer patterns. The RD lowered body weight by 26% and increased maximum life span by approximately 15%. The incidence of the most prevalent cancer, plasma cell neoplasm, was higher in RD mice (66%) than in ND mice (41%). Thus, DHEAS, as administered here, influenced neither cancer nor longevity at two caloric intakes. In contrast, CR from middle age increased longevity, the age at which tumor-bearing mice died, and the percentage of mice dying with cancers, suggesting that CR may retard promotion and/or progression of existing lymphoid cancers.
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PMID:Dietary intervention at middle age: caloric restriction but not dehydroepiandrosterone sulfate increases lifespan and lifetime cancer incidence in mice. 1019 41

Antibody production against the trehalose 6,6'-dimycolate (TDM, cord factor) of Rhodococcus ruber, a non-pathogenic species of the Actinomycetales group, was investigated in mice by repeated intraperitoneal injection of TDM in water-in-oil-in-water micelles without carrier protein. The antigenic TDM was isolated and purified chromatographically from the chloroform-methanol extractable lipids of R. ruber. The hydrophobic moiety of this TDM was composed of two molecules of monoenoic or dienoic alpha-mycolic acids with a carbon chain length ranging from C44 to C48 centering at C46. To detect the antibody, an enzyme-linked immunosorbent assay (ELISA) system was employed using plastic plates coated with TDM. The antibody reacted against the TDM of R. ruber. The antibody was reactive in similar fashion against glycosyl monomycolates differing in the carbohydrate moiety, such as that of glucose mycolate (GM) and mannose mycolate (MM), obtained from R. ruber. Moreover, the antibody reacted against mycolic acid methyl ester itself when it was used as the antigen in ELISA, and trehalose did not absorb the antibody to TDM or inhibit the reaction. These results indicate that the epitope of TDM recognized by the antibody is mycolic acid, an extremely hydrophobic part of the molecule. Next, we prepared monoclonal anti-TDM antibody (moAb) in mice myeloma cells to examine its biological activities and the role of humoral immunity in mycobacterial infection. MoAb reacted against the TDM, glycosyl mycolate, and mycolic acid methyl ester in ELISA in the same manner as our polyclonal antibody did. The administration of moAb suppressed granuloma formation in the lungs, spleen, and liver induced by TDM and inhibited the production of interleukin-1 (IL-1) and chemotactic factor, which is reported to precede granuloma formation.
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PMID:Production and partial characterization of antibody to cord factor (trehalose 6,6'-dimycolate) in mice. 1052 97

Although common cutaneous lesions in myeloma-associated systemic amyloidosis are petechiae, purpura, ecchymoses, plaques, waxy, translucent or purpuric papules or nodules, we encountered an unusual case of myeloma-associated amyloidosis with multiple cystic nodules. We isolated amyloid substance from the cutaneous cystic nodules of this patient and characterized it ultrastructurally, immunologically, and biochemically. Electron microscopy demonstrated that amyloid substances isolated by distilled water were principally straight and non-branching fibrils with a diameter of 8 to 10 nm, which was morphologically similar to amyloid fibrils. SDS-PAGE showed that these fibrils consisted of the 20 kDa and 29 kDa peptides, which reacted with the antibody to kappa light chain of immunoglobulin by immunoblot study. Partial amino acid sequence of N-terminal residues of this 20 kDa peptide showed a homology to kappa immunoglobulin light chain of variable subgroup I. These results suggest that amyloid fibrils in this unusual case with cutaneous cystic nodules may be derived from kappa I light chain of immunoglobulin.
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PMID:Partial amino acid sequence of an amyloid fibril protein from unusual cutaneous cystic lesions in myeloma-associated amyloidosis. 1058 30


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