Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A long-term epidemiological genetic study was conducted in which all new patients were evaluated prospectively at the Foundation for Depression and Manic Depression and two Lithium/Affective Disorders clinics at the Columbia-Presbyterian Medical Center between the years of 1972 and 1978. All patients met Feighner, RDC and DSM III criteria for Major Depressive Disorder after initial clinical screening interviews and were further subtyped using the Fieve-Dunner 7-point criteria. All 604 probands and 90% of 2711 first-degree relatives were interviewed blindly by diagnosticians trained in the use of the SADS structured interview. Cumulative morbid risk in parents, siblings and children of 490 bipolar probands was 15.6 +/- 3% and 14.0 +/- 1.7% in the first-degree relatives of 114 unipolar probands. A number of biological and genetic marker studies were simultaneously performed on samples of the overall population. The enzymes catechol O-methyltransferase and dopamine beta-hydroxylase, and the dexamethasone suppression test (SDT) did not show any biological marker value for outpatients even though both enzymes were determined to have hereditability. The HLA system, monoamine oxidase and acetylcholinesterase segregated differently from normal controls in samples of the patient population. The positive association findings with monoamine oxidase and the HLA system conflicted with the positive findings of other investigators, leaving doubtful their biological marker value. Red cell acetylcholinesterase was found to be significantly lower in affective disorder patients than in controls. This positive association finding was recently replicated by Mathews et al. (1982) but needs further confirmation. Using 28 blood group markers, a prior association study between the trait defining susceptibility to affective disorder and the genetic marker was positive for haptoglobin GC, and properdinfactor B, confirming earlier findings. Using the sib-pair method on the remaining 25 blood groups revealed that none other than peptidase A showed significant linkage with affective disorder since one significant finding is expected by chance. We conclude from the overall morbid risk data and segregation analyses that bipolar manic-depressive illness is a spectrum disease inherited through a multifactorial mode of genetic transmission (which is not synonymous with polygenetic inheritance) with possible genetic heterogeneity and find no evidence for X-linkage. Additional studies with acetylcholinesterase, haptoglobin, GC, and properdin-factor B are needed to confirm their positive biological/genetic marker value suggested by our long-term epidemiological study.
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PMID:Search for biological/genetic markers in a long-term epidemiological and morbid risk study of affective disorders. 651 12

In a previous study, we demonstrated that parathion suppressed both the primary IgM and IgG response to sheep erythrocytes (SRC) in inbred and outbred mice (G. P. Casale, S. D. Cohen, and R. A. DiCapua, 1982, toxicologist 2, 94). Suppression occurred after a dosage which produced cholinergic effects but was absent after a lower dosage which did not produce cholinergic signs. This information suggested that immunosuppression might be mediated indirectly as a result of toxic chemical stress. The present study evaluated the relationship between the anticholinesterase action of parathion, malathion, and dichlorvos (DDVP) and their effects on the primary humoral response to SRC. Male C57Bl/6 mice were given a single dose of parathion (16 mg/kg, po), malathion (720 mg/kg, po), or DDVP (120 mg/kg, po) 2 days after immunization with SRC. Two days later, tissues were removed for cholinesterase (CHE) assay and enumeration of splenic antibody-forming cells (PFC). All three compounds produced moderate to severe cholinergic poisoning. DDVP produced cholinergic signs beginning 1/2 hr after dosing and lasting 1/2 to 1 hr. This profile was associated with a rapid but transient inhibition of brain CHE activity. In contrast, malathion and parathion produced prolonged cholinergic poisoning (4 to 7 hr) and prolonged suppression of brain CHE activity. All three compounds suppressed the primary IgM response. However, when they were given as multiple lower doses, none of the compounds suppressed the primary IgG response. These latter treatments produced no cholinergic signs. The cholinomimetic agent, arecoline (65 mg/kg, ip) produced a short-lived cholinergic crisis but no IgM suppression. Sustained-release arecoline produced prolonged cholinergic poisoning (3 to 5 hr) and reduced the number of IgM PFC to 50% of control. These results demonstrated that organophosphate-induced immunosuppression was associated with severe cholinergic stimulation. The immunosuppression may result from direct action of acetylcholine upon the immune system or it may be secondary to the toxic chemical stress associated with cholinergic poisoning.
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PMID:The effects of organophosphate-induced cholinergic stimulation on the antibody response to sheep erythrocytes in inbred mice. 685 60

Fenitrothion was administered orally to mice or rats in daily doses of up to 1/25 of the LD50 for 14 days, and numbers of splenic plaque-forming cells against sheep red blood cells (SRBC-PFC), one of the most common immune parameters, were measured. Splenic SRBC-PFC number was suppressed by fenitrothion only in rats which received 30 mg/kg body weight (bw) of the compound. Other immune parameters, including the arthus reaction, delayed-type hypersensitivity, and activities of macrophages and natural killer cells in rats, were not influenced by fenitrothion. Adrenal hyperfunction manifesting as increased organ weight and elevated plasma corticosterone level was noted along with strong cholinergic signs in rats which received 30 mg/kg bw of fenitrothion. At lower doses such as 3 or 0.3 mg/kg bw of fenitrothion, rats had no strong cholinergic signs, adrenal hyperfunction, or evidence of immunosuppression despite significant suppression of systemic cholinesterase (ChE) activities. In mice, no suppression of SRBC-PFC number or mixed lymphocyte reaction was noted even at the highest dose (40 mg/kg bw) of fenitrothion, at which significant suppression of systemic ChE activities but no cholinergic signs were noted. These findings strongly suggest that the immunosuppressive effect of fenitrothion noted in rats was due to systemic, potent cholinergic stress and that fenitrothion has no immunotoxicity in mice and rats.
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PMID:Immunotoxicological insignificance of fenitrothion in mice and rats. 892 43