Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heavy metals and chloro-organic compounds can influence female fertility at every phase of reproduction. They may induce hormonal disorders, preventing ovulations and pregnancies. They can also result in abortions and fetal malformations. For this reason, the urinary excretion of heavy metals was measured after oral load with the chelating agent dimercaptopropanesulfonate (Dimaval) in women with hormonal irregularities. In addition, blood was examined for various polychlorinated compounds (polychlorinated biphenyls - PCB -, hexachlorocyclohexane - HCH -, pentachlorophenole - PCP -, hexachlorobenzol - HCB -, dichlordiphenyltrichloroethane - DDT -, dichlorodiphenylethane - DDE -, tetrachlorodiphenylethane - DDD -). Mercury contaminations were seen most commonly and correlated significantly with the number of amalgam fillings and with the release of mercury while chewing. The latter was demonstrated with the so-called chewing-gum test. Women with hormonal disorders or alopecia had, on the average, the highest mercury excretion during the wash-out test. Cadmium excretion was pronounced for the following groups of women: those with technical professions, those suffering from thyroid dysfunctions, and those with habitual abortions and uterine fibroids. With increasing age, pesticide concentrations of the blood rose significantly. Women with endometriosis and with antihyroidal antibodies had significantly higher PCB values. Despite therapeutic intervention, fewer women with elevated DDT/DDE/DDD values conceived when compared to those with lower values. alpha-HCH concentrations were often elevated in women with uterine fibroids. With increasing PCP levels pregnancies often ended in abortion. Results of this investigation indicate that women with hormonal irregularities or specific fertility disorders should be examined for heavy metal and pesticide contamination prior to hormone treatment.
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PMID:[The limits of hormone substitution in pollutant exposure and fertility disorders]. 128 83

Rat brain cortex synaptosomes pre-incubated with [3H]norepinephrine were used (1) to provide evidence that part of the NMDA receptors mediating stimulation of norepinephrine (NE) release are located on the noradrenergic varicosities themselves, (2) to characterize these receptors and (3) to examine whether ethanol specifically inhibits the NMDA-evoked NE release via a presynaptic site of action. In synaptosomes superfused with Mg(2+)-free Krebs-Henseleit solution, NMDA (2-min exposure) stimulated tritium overflow in a concentration- and glycine-dependent manner. The stimulatory effect of NMDA was not altered by tetrodotoxin but was abolished by omission of Ca2+ from the superfusion fluid and was considerably reduced in the presence of 1.2 mM Mg2+. DL-(E)-2-Amino-4-methyl-5-phosphono-3-pentanoic acid (CGP 37849; a competitive NMDA receptor antagonist) produced a parallel shift of the concentration-response curve for NMDA to the right, whereas dizocilpine (MK-801; an antagonist at the phencyclidine, PCP, recognition site of the NMDA-gated ion channel) reduced the maximum effect of NMDA. Ethanol inhibited the NMDA-evoked tritium overflow in a concentration-dependent manner. In contrast, in synaptosomes superfused with Ca(2+)-free Krebs-Henseleit solution containing 15 mM K+ throughout, ethanol did not affect the tritium overflow evoked by 2 min introduction of 75 microM Ca2+ into the superfusion fluid. This Ca(2+)-evoked overflow was also not altered by tetrodotoxin and dizocilpine, but was inhibited by the inorganic Ca2+ channel antagonist Cd2+.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Presynaptic site of action underlying the ethanol-induced inhibition of norepinephrine release evoked by stimulation of N-methyl-D-aspartate (NMDA) receptors in rat cerebral cortex. 135 86

This review focuses of industrial chemicals that research has indicated may adversely affect human male reproductive capacity. The study of male reproductive toxicity is impeded by a dearth of clinical endpoints. Males lack an obvious and easily measurable reproductive cycle, and the primary clinical indicator, semen analysis, offers unsure clues to reproductive performance. However, progress is being made in developing and evaluating tests to identify chemical hazards and estimate human health risks. Agents with confirmed adverse effects of male reproduction include carbon disulfide, dibromocklopropane, lead, and oral contraceptives. Agents with inconclusive effects include anesthetic gases, arsenic, benzene, boron, cadmium, carbaryl, chlordecone, chloroprene, DNT and TDA, ethylene dibromide, manganese, mercury, pesticides, PCP, radiation ionizing and nonionizing, solvents, dioxin, and vinyl chloride. Finally, agents with no observed adverse effects include epichlorohydrin, glycerine, benzoic acid, and polybrominated biphenyls. The literature suggests a need for further research in the following areas: 1) chemicals that are reactive and capable of covalent interactions in biological systems, 2) chemicals defined as mutagens and/or carcinogens in short-term laboratory tests, 3) chemicals demonstrated to cause aneuploidy or other chromosomal aberrations, 4) chemicals that affect sperm motility in vitro, 5) chemicals that share hormonal activity or affect hormone action, and 6) chemicals that act directly or indirectly to affect the hypothalamo-pituitary-gonadal axis.
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PMID:Occupational exposures associated with male reproductive dysfunction. 240 59

The increasing number of discussions on the influence of toxic environmental factors, including SIDS, prompted systematic postmortem chemical-toxicological investigations to be carried out on 54 SIDS cases and 2 control cases of the same age group. Tissue levels of arsenic, lead, cadmium, mercury, and pentachlorphenol, as well as other organic noxious agents, were measured in several organs. In addition, the COHb concentrations were determined. In spite of the widely scattered values, the extreme levels measured and the arithmetic means and median averages of As, Pb, Cd, Hg, PCP, and COHb had no more range in concentrations than can be expected for toxic effects - according to present knowledge anyway. It was observed that infants from an urban environment showed no greater concentration of noxious agents than did infants from rural regions. There were also no differences between SIDS cases and the controls, nor was there a correlation between infections of the respiratory system that are often morphologically detected - including laryngitis - and higher concentrations of these agents in the organs of SIDS cases.
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PMID:[Toxic environmental factors in sudden infant death (SIDS)]. 360 64

In a previous study a simple algorithm was presented for effect assessment on secondary poisoning of birds and mammals. This algorithm (MPC = NOECfish-eater/BCFfish) was drawn up by analyzing a two-step aquatic food chain (water-fish-bird/mammal). The algorithm was used to test whether quality criteria set for surface water, based on effect assessment for aquatic organisms, constitute a "safe" level for secondary poisoning. The present study analyzes whether this algorithm can equally well be used for effect assessment in a terrestrial food chain. The pathway soil-earthworm-bird/mammal was used as an example for a terrestrial food chain. Literature data of six selected compounds (lindane, dieldrin, DDT, PCP, cadmium, and mercury) on both bioconcentration factors for earthworms and toxicity data for birds and mammals were studied. Important differences were found between BCFs for this terrestrial pathway and BCFs for the aquatic pathway analyzed in the previous study. It was found that BCFs for earthworms were more dependent on soil-related properties than on compound-specific properties. Hence, it was concluded that the algorithm MPC = NOECworm-eater/BCFworm can be used only for effect assessment on terrestrial food chain in defined situations. By calculating maximum permissible concentrations for secondary poisoning (MPCsp) for a standard soil situation and comparing these to MPCs for soil organisms, it was concluded that secondary poisoning could be a critical pathway for cadmium and methyl mercury. For methyl mercury secondary poisoning in an aquatic food chain was also a critical pathway. Secondary poisoning of fish-eating birds and mammals is not likely to occur for cadmium at concentrations in water below the MPC calculated for aquatic organisms.
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PMID:Presentation of a general algorithm to include effect assessment on secondary poisoning in the derivation of environmental quality criteria. 2. Terrestrial food chains. 751 80

The mineralization of [14C]acetate was studied in bottles with fresh soil and groundwater. Addition of toxicants inhibited the formation of 14CO2 and dose-effect curves were obtained. The acetate mineralization was not inhibited by zinc, cadmium, K2Cr2O7, chloropyrifos, and paraquat in an acid sandy soil at 1000 mg/kg dry soil. The IC10 is the toxicant concentration which inhibits 10% of the initial mineralization rate. The IC10 concentrations for 3,4-dichloroaniline, triphenyltin, and orthoxylene were 48, 96, and 730 mg/kg, respectively, in the acid sandy soil. The IC10 of pentachlorophenol was measured in samples from the acid sandy soil and in several other soil and subsoil samples. The geometrical mean of the 13 IC10 values was 16 mg pentachlorophenol/kg. A statistical method was used to calculate the PCP concentration above which 5% of the most sensitive acetate-mineralizing communities in all soils are influenced. The best estimate of this concentration is 0.3 mg PCP/kg but to be on the safe side the 95% confidence level of this concentration is 25 micrograms/kg.
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PMID:Toxic effects of pentachlorophenol and other pollutants on the mineralization of acetate in several soils. 769 30

A general algorithm for effect assessment on secondary poisoning for birds and mammals is presented. This algorithm (Maximum Permissible Concentration = NOECbird/mammal/BCF) was drawn up by analysing an aquatic food chain (water--fish--bird or mammal) and a terrestrial food chain (soil--worm--bird or mammal). NOECs and bioconcentration factors (BCFs) were collected for a set of selected compounds: lindane, dieldrin, cadmium and mercury in both water and soil, PCB153 only in water and DDT and PCP only in soil. BCFs for the terrestrial pathway are frequently < 1 and rarely above 10, though for the aquatic pathway BCFs up to 10(4) were found for the same compounds. By calculating MPCs for fish-eaters and comparing these to MPCs calculated for aquatic organisms, secondary poisoning could be a critical pathway for methyl-mercury and PCB153. For lindane the conclusion depends on whether a separate or combined data set is chosen for birds and mammals. By calculating MPCs for a standard soil situation and comparing these to MPCs for terrestrial organisms, secondary poisoning could be a critical pathway for cadmium and methyl-mercury.
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PMID:Presentation of a general algorithm to include secondary poisoning in effect assessment. 810 16

This paper defines the culture conditions of the ciliate Spirostomum teres and assesses its sensitivity to some xenobiotics for the development of a new low-cost microbiotest. The model was selected for its ubiquitous distribution, large size for a unicellular species, easy culture in holoxenic medium, moderate generation time, and high sensitivity to pure toxicants. The influence of different culture waters, inocula of ciliates, food, temperature, light, and darkness on the growth of the ciliate population was tested. The shortest generation time (average 39 h) was obtained for cultures incubated at 25 degreesC in the dark with an inoculum of 4 ciliates per ml in 25 ml of Volvic mineral water containing 8 boiled wheat grains, when preincubated without ciliates for the previous week. Under these conditions, it was possible to obtain about 3000 ciliates/ml 3 weeks later. Acute toxicity tests (24-h LC50) were carried out for CuSO4, HgCl2, CdCl2, K2Cr2O7, ZnSO4, Pb(NO3)2, thiram, carbaryl, lindane, parathion, parathion methyl, paraoxon, 2, 4,6-trichlorophenol, and sodium pentachlorophenolate (Na-PCP). Very high sensitivity of the model to Hg2+, Cu2+, Cd2+, thiram, and Na-PCP was established. Comparison of its sensitivity with that of Microtox (current results), Daphnia Magna, Tetrahymena pyriformis, Colpidium campylum, and murine fibroblasts (data from literature) confirms the high sensitivity of the model, especially to heavy metals. Easy-to-perform, cost-effective, and sensitive bioassays using S. teres are suitable for risk assessment and early detection of toxicity in fresh water.
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PMID:A new low-cost microbiotest with the Protozoan spirostomum teres: culture conditions and assessment of sensitivity of the ciliate to 14 pure chemicals. 979 74

Vascular endothelial growth factor (VEGF) is a dimeric protein which induces formation of new blood vessels (angiogenesis) through binding to VEGF-receptor-2 tyrosine kinase (VEGFR2 TK) or KDR (kinase insert domain-containing receptor) on the surface of endothelial cells. Angiogenesis has been shown to be essential for malignancy of tumors; therefore, VEGFR2 TK is a potential therapeutic target for the treatment of cancer. Sequence homology studies indicate that VEGFR2 TK contains three domains: extracellular (ligand-binding domain), transmembrane, and intracellular (catalytic domain). In this work, the catalytic domain of VEGFR2 TK was cloned and expressed in a soluble active form using a baculovirus expression system. In the absence of ligand, the enzyme is shown to catalyze its autophosphorylation in a time-dependent and enzyme-concentration-dependent manner, consistent with a trans mechanism for this reaction. Mass spectrometry analysis revealed incorporation of 5.5 +/- 0.5 mol of phosphate/mole of enzyme (monomer). In addition, the enzyme was shown to catalyze phosphorylation of a synthetic peptide, poly(E4Y). Using poly(E4Y) as substrate, the kinetic constants of both native and phosphorylated enzyme were determined. Enzyme phosphorylation increased catalytic efficiency of the enzyme by at least an order of magnitude. Furthermore, the enzyme was shown to catalyze the reverse reaction using phospho-poly(E4Y) as substrate. Cd2+ was found to be an inhibitor of the enzyme. Kinetic studies revealed that inhibition by Cd2+ was competitive with respect to Mg2+ and noncompetitive with respect to MgATP. These results indicate that Cd2+ competes for a second metal-binding site. Therefore, the reaction catalyzed by this enzyme was treated as a terreactant system. The kinetic mechanism of VEGFR2 TK was elucidated through the use of steady-state kinetic studies. According to these studies, the enzyme binds Mg2+ and MgATP in a random fashion followed by ordered addition of the peptide substrate. The release of product is also ordered, with MgADP being released last. The order of substrate binding was confirmed by using AMP-PCP, a dead-end inhibitor.
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PMID:Characterization and kinetic mechanism of catalytic domain of human vascular endothelial growth factor receptor-2 tyrosine kinase (VEGFR2 TK), a key enzyme in angiogenesis. 984 50

The German Environmental Survey (GerES) is a large-scale, representative population study that has been carried out three times up to now with a time interval of about 7 years. GerES I was performed in 1985/1986, GerES IIa in 1990/1991 in West Germany, and GerES IIb in 1991/1992 in East Germany, the former German Democratic Republic (GDR). In GerES II, blood, urine, and scalp hair samples of 4021 adults aged 25-69 years and of 736 children aged 6-14 years were analysed as well as environmental samples (house dust, drinking water, indoor and personal air, diet). Characteristics of the frequency distributions of the substances analysed in the different media were calculated. The geometric mean (GM) for lead, cadmium, and mercury in the blood of adults amounted to 45.3, 0.36, and 0.51 microg/l, respectively. The corresponding values of arsenic, cadmium, and mercury in urine were 6.3, 0.29, and 0.54 microg/l, respectively. The concentrations of lead in blood, cadmium in blood and urine, and mercury in blood are lower in children than in adults. The GM ofpentachlorophenol (PCP) in urine of adults was 2.67 microg/l and in urine of children, 4.15 microg/l. These results of GerES II were compared with the so-called HBM values which represent health-based exposure guidelines and have been defined by the Human Biomonitoring Commission (HBC) of the Federal Environmental Agency, interalia for lead in blood, cadmium in urine, mercury in blood and urine, and PCP in urine. They also provided asound basis for the setting of reference values to describe the status of the German population. A total of 1.8% and 0.6% of the German females in child-bearing age had a level of lead in blood higher than HBM-I (100 microg/l) and HBM-II ( 150 microg/l), respectively. One percent of the children had a blood lead level above HBM-I. House dust and drinking water were analysed to characterise exposure in the domestic environment. Arsenic, cadmium, and lead deposition in homes amounted to 5.4 ng/(m2 day), 11.7 ng/(m2 day), and 0.29 microg/(m2 day), respectively. In the content of vacuum cleaner bags, concentrations were 2.1,0.9, and 5.9 microg/g. PCP, lindane and permethrin could be detected in the house dust of most German households. The pollutant load of the drinking water is significantly influenced by the corrosion of pipe materials and fittings. The new EC limit value of 10 microg/l for lead was exceeded in 7.7% of the first draw samples. The relatively high percentage (14%) of samples from East Germany that exceeded the current German guideline value for formaldehyde of 0.1 ppm in indoor air may be explained by the widespread use of contaminated particleboard in the former GDR.
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PMID:The German Environmental Survey 1990/1992 (GerES II): reference concentrations of selected environmental pollutants in blood, urine, hair, house dust, drinking water and indoor air. 1114 Apr 39


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