SUMMARY1. The distribution of acetylcholine receptors (AChR) at frog cutaneous pectoris neuromuscular junctions was studied quantitatively using [125I]a-bungarotoxin (a-BTX) labelling and EM autoradiography.2. We found that, as in mouse end-plates, the AChR is localized uniformly along the thickened post-junctional membrane. In the frog muscle this specialized membrane constitutes approximately the top 50 % of the junctional folds.3. The receptor site density is 26,000 + 6000 sites/,um2 on the thickened postjunctional membrane and falls sharply to 50 sites/fum2 within 15 Itm from the axon terminal.4. a-BTX site density on the presynaptic axonal membrane was directly determined to be at most 5 % of the value on the thickened post-junctional membrane.5. The high post junctional AChR site density leads us to conclude that: (a) each quantum of ACh needs to spread only over a very small post-junctional area (to be called the 'critical area') before it encounters as many AChR (plus AChE) sites as there are ACh molecules in the quantum (for a packet of 104 ACh molecules this critical area is-03 #um2), (b) the average concentration of ACh prevailing in
Context
Lead is a ubiquitous neurotoxicant, and adverse cognitive and behavioral effects are well documented in children and occupationally exposed adults but not in adults with low environmental exposure.
Objective
To investigate the association of current blood lead levels with three common psychiatric disorders, major depression, panic, and generalized anxiety, among young adults.
Design
Cross-sectional epidemiologic survey.
Setting
Representative sample of non-institutionalized United States adults.
Participants
A total of 1,987 respondents of age 20–39 years to the National Health and Nutrition Examination Survey conducted from 1999 to 2004.
Main Outcome Measures
Twelve-month DSM-IV criteria-based diagnoses of major depressive disorder, panic disorder, and generalized anxiety disorder assessed by the Composite International Diagnostic Interview.
Results
Mean blood lead level was 1.61 μg/dL (SD 1.72, range 0.3–37.3 μg/dL). Increasing blood lead level was associated with higher odds of major depression (p for trend 0.05) and panic disorder (p for trend 0.02), but not generalized anxiety disorder (p for trend 0.75), after adjustment for sex, age, race/ethnicity, education, and poverty-income ratio. Persons with blood lead level in the highest quintile had 2.3 times the odds of major depressive disorder (95% CI 1.13 – 4.75) and 4.9 times the odds of panic disorder (95% CI 1.32 – 18.48) as those in the lowest quintile. Cigarette smoking was associated with higher blood lead level and the outcomes, but models excluding current smokers also resulted in significantly increased odds for major depression (p for trend 0.03) and panic disorder (p for trend 0.01) with higher blood lead quintile.
Conclusions
In this sample of young adults with low levels of lead exposure, higher blood lead was associated with increased odds of major depression and panic disorder. Exposure to lead at levels generally considered safe could result in adverse mental health outcomes.
KEY WORDSAcetylcholine receptor, Junctional folds
ABSTRACTSeveral methods of analyzing EM autoradiograms are now available. Two such procedures, the grain density distribution (or histogram) method and the mask method use the resolution of the EM autoradiographic technique to generate grain distributions expected from postulated sources, and compare these with the observed grains in the autoradiograms. These two methods are here compared in the analysis of label on linear sources: the distribution of labeled acetylcholine receptor (AChR) down the postjunctional folds of lizard and frog neuromuscular junctions. The receptors were labeled with I-25-a-bungarotoxin and the autoradiograms coated with the high resolution Kodak emulsion 129-01. We found that both methods gave similar results in confirming that the bulk of the AChR is concentrated on the thickened region of the membrane at the top -2000 A of the junctional folds, and that there may be a gradient of receptor concentration down the folds. The grain density distribution method is simpler, but does not lend itself easily to quantifying the extent of deviation from simple models. Although computer graphics is not necessary for either method, its use allows the expected grains from linear sources to be generated quickly, making the mask analysis a feasible routine method for assigning the extent of label in different membrane regions.
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