Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

beta 2-Microglobulin is a low molecular weight protein that is found in most biological fluids. It was originally isolated from urine of cadmium-poisoned patients. Its amino acid sequence was established and shown to be structurally related to immunoglobulin constant domains. With the aid of antibodies specific against beta 2-microglobulin, the protein was detected on the membranes of all nucleated cells, normal and neoplastic. Measuring the quantity of beta 2-microglobulin showed that high levels are present in patients with renal tubular deficiencies and several other pathological conditions including neoplastic diseases. Extremely high levels were detected in seminal fluid and colostrum. Despite the structural relationship to immunoglobulins, no immunological relationship was demonstrated with these proteins using antibodies specific for beta 2-microglobulin. However, such antibodies are cytotoxic to all cells carrying beta 2-microglobulin on their surfaces. The discovery that beta 2-microglobulin is an integral part of the histocompatibility antigens of human and murine origin stimulated further research and interest in this molecule. Several groups of investigators have shown that beta 2-microglobulin is the low molecular weight chain and is noncovalently bound to a high molecular weight chain which carries the histocompatibility antigens. The structure of the histocompatibility antigens of lymphocytes (HLA) was shown by immunochemical as well as biological methods, and it is now well accepted. The antibodies against beta 2-microglobulin are extremely useful in the isolation of the histocompatibility antigens for sequence studies. Furthermore, the antibody to beta 2-microglobulin revealed that other structures may be bound to beta 2-microglobulin such as phytohemoagglutimin (PHA) receptors, mixed lymphocyte culture (MLC) antigens, etc. Murine thymus leukemia (TL) antigen also contains beta 2-microglobulin as an integral part of its structure; other tumor antigens may have a similar structure. Through all these studies, beta 2-microglobulin emerged as the best known membrane protein that can serve as a model for study of the arrangement and the function of the cell membrane.
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PMID:beta 2-Microglobulin: methods and clinical applications. 8 22

In view of the marked antitumor activity of 3-deazauridine, the synthesis of 4-(beta-D-ribofuranosyl)-1,3-dihydroxybenzene (1,3-dideazauridine) and its dibenzyl derivative was carried out. 4-Bromo-1,3-dihydroxybenzene was converted to its dibenzyl derivative, which, upon reaction with n-butyllithium followed by treatment with anhydrous cadmium chloride, gave bis(1,3-dibenzyloxyphenyl-4)cadmium. Condensation of this intermediate with 2,3,5-tri-O-benzoyl-D-ribofuranosyl chloride in refluxing toluene, and subsequent removal of the protecting benzoyl groups, afforded 4-(beta-D-ribofuranosyl)-1,3-dibenzyloxybenzene which, upon catalytic hydrogenation over Pd/C, furnished the desired 4-(beta-D-ribofuranosyl)-1,3-dihydroxybenzene. The beta configuration at the anomeric center was established by NMR and hydrogen bonding studies. 4-(Beta-D-ribofuranosyl)-1,3-dibenzyloxybenzene inhibited the growth of leukemia L1210 cells by 50% at 7 x 10(-6) M, and that of mammary carcinoma TA3 cells at 5 x 10(-5) M. Dideazauridine itself was less active, inhibiting the leukemia L1210 but not the TA3 cells at 1 x 10(-4) M, but the compound was significantly active against herpes simplex (type I) virus in vitro.
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PMID:Synthesis and biological activity of 4-beta-Iribofuranosyl-1,3-dihydroxybenzene ("1,3-dideazauridine"). 16 82

The per-capita intakes of zinc, cadmium, copper and of chromium were estimated from food consumption data in 28 countries and were found to correlate directly with the age-corrected mortalities from cancers of intestine, prostate, breast, leukemia, skin and of other organs, suggesting that the anticarcinogenic effect of selenium is counteracted by other trace elements. Similarly calculated dietary intakes of manganese are inversely correlated, particularly with the mortalities from cancer of pancreas, an organ normally known to contain high concentrations of this element. Arsenic intakes correlate inversely with the male lung cancer mortalities. A number of other direct and inverse associations were observed which suggest that trace elements in the human diet may hav both benign and adverse effects on tumor development. The zinc concentrations in whole blood collected from healthy donors in the U.S. correlate directly with regional mortalities from cancers of intestine, breast and of other sites. The origin of these associations is discussed primarily in terms of the seleium-antagonistic effect of zinc and of some of the other elements considered. Results of animal experiments and of other studies are cited which support hypotheses that link human cancer development to possible deficiencies or excesses in the dietary trace element intakes.
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PMID:Cancer mortality correlation studies--IV: associations with dietary intakes and blood levels of certain trace elements, notably Se-antagonists. 85 92

Lysozyme [EC 3.2.1.17] was purified from human tears, serum, and urine of acute monocytic leukemia patients, renal disease patients, and residents in cadmium-polluted areas of Tsushima Island using an affinity adsorbent containing lysozyme-lysate of Micrococcus lysodeikticus cell walls as the ligand. By means of this procedure, leukemia lysozyme was purified 100- to 200-fold with an activity recovery of 80%. It was crystallized at pH 10. This purified preparation appeared homogeneous in disc electrophoresis and showed a specific activity 2.5-fold higher than that of crystalline lysozyme from hen egg-white. Tear lysozyme was also purified to a nearly homogeneous state while the enzymes from normal serum and urine of a nephrosis patient and of residents in cadmium-polluted area were still disc electrophoretically heterogeneous and showed low specific activity as compared with purified leukemia lysozyme.
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PMID:Affinity chromatographic purification of human lysozyme, with special reference to human leukemia lysozyme. 107 Apr 87

Several of our recent studies in rats indicate an association between exposure to cadmium and haematopoietic tumours. In the first study, male WF rats received dietary cadmium (0-200 micrograms/g cadmium as cadmium chloride) for up to 77 weeks. A dose-related increase in large granular lymphocyte (LGL) leukaemia was observed with a maximal incidence in rats fed 100 micrograms/g cadmium. In a second study, male F344 rats received a single high dose of cadmium chloride (30 mumol/kg, s.c.) and were observed for 90 weeks. The high natural incidence of leukaemia in these rats (24%) was markedly reduced (6%) by this dose of cadmium. The paradoxical effects of cadmium on haematopoietic tumours may be the result of a dose-related spectrum of lymphotoxicity ranging from cell-specific cytotoxicity and carcinogenicity to destruction of key progenitor cell populations.
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PMID:Induction of tumours of the haematopoietic system by cadmium in rats. 130 67

The effect of chronic dietary zinc deficiency on the carcinogenic potential of dietary cadmium was assessed in male Wistar (WF/NCr) rats. Groups (n = 28) of rats were fed diets adequate (60 ppm) or marginally deficient (7 ppm) in zinc and containing cadmium at various levels (0, 25, 50, 100, or 200 ppm). Lesions were assessed over the following 77 weeks. Zinc deficiency alone had no effect on survival, growth, or food consumption. Cadmium treatment did not reduce survival or food consumption and only at the highest doses of cadmium (100 and 200 ppm) was body weight reduced (maximum 17%). The incidence of prostatic proliferative lesions, both hyperplasias and adenomas, was increased over that seen in controls (1.8%) in both zinc-adequate (20%) and zinc-deficient rats (14%) fed 50 ppm cadmium. The overall incidence for prostatic lesions for all cadmium treatment groups was, however, much lower in zinc-deficient rats, possibly because of a marked increase in prostatic atrophy that was associated with reduced zinc intake. Cadmium treatment resulted in an elevated leukemia incidence (maximum 4.8-fold over control) in both zinc-adequate and zinc-deficient groups, although zinc deficiency reduced the potency of cadmium in this respect. Testicular tumors were significantly elevated only in rats receiving 200 ppm cadmium and diets adequate in zinc. Both zinc-deficient and zinc-adequate groups showed significant positive trends for development of testicular neoplasia with increasing cadmium dosage. Thus, oral cadmium exposure is clearly associated with tumors of the prostate, testes, and hematopoietic system in rats, while dietary zinc deficiency has complex, apparently inhibitory, effects on cadmium carcinogenesis by this route.
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PMID:Carcinogenicity of oral cadmium in the male Wistar (WF/NCr) rat: effect of chronic dietary zinc deficiency. 142 9

Thirty-eight workers from a factory producing nickel-cadmium and other types of batteries came to us for medical evaluation. They included 21 women and 17 men (seniority 2-20 years, age range 31-63 years), and represented a self-selected subset of 700-900 ever-employed and 200+ recently or currently employed workers in the factory. Thirty-four worked on the nickel-cadmium assembly line. Symptoms and signs included: headache in 34; weakness, fatigue and lassitude in 26; dizziness in 16; pruritus and skin eruptions in 37; gingivitis, teeth loss and caries in 34; nasal congestion, nosebleeds and anosmia in 30; cough, phlegm production, wheezing and shortness of breath in 26; "asthma" in 14; bone pain in 18; urinary frequency, beta 2 microglobulinuria and kidney stones in 17; and sterility or multiple abortions (33) in 8 of 21 women. One additional patient had died from an "amyotrophic lateral sclerosis-like syndrome", while CT scans in six workers revealed brain atrophy. One other worker had leukemia, and two had died from cancer (lung and pancreas). Those who had worked for more than 10 years had more symptoms and signs than shorter-term employees, especially neurological illness, bone pain and urinary tract problems, including beta 2 microglobulinuria. Past blood and urinary cadmium levels were in the range of 1.6-8.7 micrograms/dl and 8-306 micrograms/l, respectively. Our findings indicated that: a) health risks for workers were not confined to the nickel-cadmium assembly line or to older workers, b) hazardous exposures still existed and illness appeared in new workers after a clean-up and intervention program, and c) exposures involved increased risks for renal disease and cancers. Finally, there is a need to control exposures and determine health risks in the full cohort of those ever employed, in the workers' children, and in the surrounding environment (air, ground, water) due to the dumping of waste from the plant.
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PMID:Medical findings in nickel-cadmium battery workers. 142 13

The carcinogenic effects of cadmium have not been thoroughly assessed in the commonly used Fischer (F344) rat. This study determined tumor incidence in various tissues of male F344/NCr rats after a single dose of cadmium. Cadmium (as CdCl2) was given sc in the dorsal thoracic midline at 30 mumole/kg to 70 8-week old male F344 rats while controls (n = 50) received saline. Rats were observed during the next 90 weeks. Early deaths (less than or equal to 32 weeks), due mostly to acute cadmium-induced hepatotoxicity, accounted for 37 of the cadmium-treated rats while no control rats died in the same period. A high incidence of injection site sarcomas (ISS) occurred in the cadmium-treated group (21 ISS/32 rats at risk; 66%) while only 1/50 occurred in controls (2%). In fact, ISS were the major cause of morbidity after 35 weeks in cadmium-treated rats. These tumors were mostly fibrosarcomas, although histiocytic and osteogenic sarcomas also occurred. Testicular interstitial cell tumors, which show a very high spontaneous incidence in this strain (41/49; 84%), were not markedly affected by cadmium (30/31; 97%). This is in sharp contrast to other strains, such as the Wistar, in which cadmium treatment is reported to cause as much as an eightfold increase in interstitial cell (Leydig cell) tumor incidence. The incidence of large granular lymphocyte (LGL) leukemia, which also occurred frequently in control F344 rats (12/47; 26%) was markedly decreased (2/31; 7%) by cadmium. Our recent studies indicate acute lymphonecrotic effects occur with cadmium in lymphoid tissues of rats, and this may be related to the suppression of the leukemia. These results indicate that cadmium is very effective in inducing ISS in F344 rats, as is the case with other strains thus far tested, and also markedly reduces spontaneous leukemia incidence.
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PMID:Chronic carcinogenic and toxic effects of a single subcutaneous dose of cadmium in the male Fischer rat. 185 89

This laboratory first provided evidence for a potential signal transduction pathway involving sphingomyelin and its derivatives (Kolesnick, R.N., and Clegg, S. (1988) J. Biol. Chem. 263, 6534-6537). Recently, this laboratory demonstrated the existence of the novel sphingolipid ceramide 1-phosphate in human leukemia (HL-60) cells. Ceramide 1-phosphate was synthesized from ceramide derived from sphingomyelin but not glycosphingolipids. This suggested that a specific pathway extended from sphingomyelin to ceramide 1-phosphate. The present studies provide additional support for this notion by demonstrating the existence of a ceramide kinase activity distinct from diacylglycerol (DG) kinase in HL-60 cells. Microsomal membranes contained a kinase activity that phosphorylated ceramide but not 1,2-DG in the presence of physiologic and higher Ca2+ concentrations (60 nM-3 mM). Kinetic analyses demonstrated an apparent Vmax for ceramide and ATP of 70 pmol.min-1.mg protein-1; apparent Km values were 45 and 25 microM, respectively. The pH optimum was within the physiologic range (pH 6-8). Magnesium but not other divalent cations (Mn2+, Ba2+, Cd2+, Zn2+) also stimulated ceramide phosphorylation. Magnesium also induced 1,2-DG phosphorylation. Since DG kinase is a Mg2(+)-stimulable enzyme that may utilize ceramide as substrate, additional studies separated calcium-dependent ceramide kinase from DG kinase activity. 1,2-DGs competitively inhibited magnesium- but not calcium-dependent ceramide phosphorylation. Hence, calcium-dependent ceramide kinase activity neither utilized DG as substrate nor was inhibited by DG. These activities were physically separable. Both activities were solubilized by n-octyl-beta-D-glucopyranoside and stabilized by glycerol. Ceramide kinase activity bound weakly to a DEAE-cellulose anion exchange column and eluted with 4-fold purification as a single peak of activity in the flow-through and 0.05 M NaCl elutions. In contrast, the majority of DG kinase activity bound more tightly and was recovered as a broad peak in the 0.2-0.35 M NaCl elutions. These studies demonstrate the existence of a ceramide kinase activity in HL-60 cells which is functionally and physically separable from DG kinase. These studies provide further support for the notion of a specific pathway from sphingomyelin to ceramide 1-phosphate.
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PMID:Characterization of a ceramide kinase activity from human leukemia (HL-60) cells. Separation from diacylglycerol kinase activity. 217 34

Our studies on the mechanism of resistance of the murine leukemia L1210-PDD line to cis-dichlorodiammineplatinum(II) (cis-DDP) have not shown why it is 10-fold more resistant to the drug than the L1210 line. For this reason we investigated metallothionein-like proteins ('MTs') in these cells. Soluble protein extracts from cultures treated for 24 h with cis-DDP, zinc sulphate or saline were anaerobically eluted from columns of chemically reduced Sephadex G-75, and the profiles of zinc, copper and platinum were determined along with those for incorporated radioactive cyst(e)ine and tyrosine. Both saline-treated cell lines contained similar levels of 'MTs', which were induced by exposure to a minimally toxic level of zinc (100 microM). Zinc induction of 'MTs' was nearly 4-fold greater in L1210 than in L1210-PDD cells. The levels of mRNA for metallothionein I (MTI) and II (MTII) in uninduced cells were measured by dot-blotting with a cDNA probe. The L1210-PDD cells contained 80% of the MTI and 41% of the MTII compared with L1210 cells, confirming the similar levels in uninduced cells. L1210-PDD cells were 2-fold more sensitive than L1210 cells to cadmium and equally sensitive to zinc. Thus, the resistance of L1210-PDD cells to cis-DDP was not associated with cross-resistance to group IIb metals, whereas their sensitivity to cadmium did reflect the relative inability of the cells to synthesize 'MTs'. The L1210 cells produced 'MTs' when treated with 0.5 and 5.0 microM cis-DDP, but the L1210-PDD cells did not when treated with 5.0-40 microM cis-DDP. Small amounts of platinum (less than 21% of the total eluted) were bound to 'MTs' in both cell lines, but platinum provided a minor portion of the 'MT'-bound metals, with zinc and copper contributing the bulk. The basis for the resistance of L1210-PDD cell to cis-DDP is neither an increased level of 'MTs' in the resistant cells nor an enhanced ability to increase the synthesis of 'MTs' after drug exposure.
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PMID:Metallothionein-like proteins and cell resistance to cis-dichlorodiammineplatinum(II) in L1210 cells. 231 Nov 68


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