Household composition, extended kinship, and reproduction in Taiwan: 1965-1985.
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China↗
Biomedical subjects
R Freedman
Publications and source records attributed to R Freedman.
Toxic effects of lead on neuronal development and function.
The effects of lead on the development of the nervous system are of immediate concern to human health. While it is clear that lead can affect neuronal development at levels of exposure within the range found in the environment, the particular mechanism of the disruption is not readily ascertained. Lack of knowledge of the mechanisms of lead-induced damaged hampers its treatment and prevention. The goal of our research is to develop a model system in which the effects of lead on central nervous system development can be demonstrated. The complexity of the brain hampers such investigations because often it is not clear if apparent toxic effects represents changes secondary to somatic changes, such as endocrine or hematological defects, that could alter brain development, or even transneuronal effects caused by toxicity at a distal site that deprives a brain area of a synaptic input needed for its proper development. A related problem is the redundancy of compensatory systems in the brain. Such system may disguise the severity of the initial toxic insult and themselves can cause functional disturbances. To study neuronal development in a system that minimizes such difficulties, we have grafted discrete brain regions derived from rat fetuses into the anterior chamber of the eye of adult hosts. The brain pieces continue organotypic development of the eye, but are isolated from possible secondary changes due to alterations in the development of the endocrine and other somatic systems because the adult host has these systems already fully developed. Similarly, effects mediated by connecting brain areas are minimized since the transplant is isolated in the anterior chamber of the eye.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic Fibers↗
The origins of the Chinese fertility decline.
Education and urbanization are shown to have been negatively correlated to marital fertility in both urban and rural China prior to the initiation of the substantial family planning programs. We maintain that early use of contraception by better educated and urban strata is a plausible cause of the observed fertility differentials because other proximate variables are unlikely. Coale's m, a presumed indicator of controlled fertility, suggests early fertility control in urban and better educated strata. The apparent preprogram beginnings of fertility control among educational and urban elites does not, however, minimize the awesome effects on fertility of the powerful Chinese family planning programs, once begun.
Adolescent↗
Electroabsorption of polyacetylene.
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Journal Article↗
Pertussis toxin lesioning of the nucleus caudate-putamen attenuates adenylate cyclase inhibition and alters neuronal electrophysiological activity.
Receptor-mediated inhibition of brain adenylate cyclase activity has been well characterized at the biochemical level. However, less understood is how these, typically modest, inhibitory effects on cyclase activity correlate with the electrophysiological activity of brain preparations. In addressing this question, we injected pertussis toxin (PT) into the nucleus caudate-putamen of intact rats, and observed a subsequent attenuated inhibition of adenylate cyclase activity in caudate membranes, which correlated with altered electrophysiological activity in this nucleus. PT completely abolished and electrophysiological activity in this nucleus. PT completely abolished and significantly reduced, respectively, dopamine D2 and opioid receptor-mediated inhibition of adenylate cyclase. In addition, pretreatment of rat caudate nuclei with PT attenuated the amount of in vitro ADP-ribosylation of 41,000 and 39,000 Da PT substrates measured in caudate membranes. Extracellular recording of the spontaneous activity of caudate neurons revealed that PT pretreatment significantly increased firing rates above those of cells recorded from sham-operated and unoperated controls. Furthermore, a significantly greater number of cells pretreated with PT displayed interspike intervals less than 50 ms, reflecting 'burst-like' activity. In short, the inactivation of G-proteins serving as PT substrates in rat caudate-putamen renders caudate cells more likely to fire spontaneously, and to fire in bursting, rather than uniform, patterns of activity. These observations suggest that PT substrates identical or similar to those which regulate adenylate cyclase, play a significant role in governing the electrophysiological behavior of intact caudate neurons.
Action Potentials↗
Kappa-bungarotoxin blockade of nicotine electrophysiological actions in cerebellar Purkinje neurons.
The agonistic actions of nicotine in cerebellum were selectively blocked by kappa-bungarotoxin depending on the cell type studied. Nicotine-induced Purkinje cell inhibitions were antagonized by the simultaneous application of this toxin. In contrast, nicotine-induced cerebellar interneuron excitations were unaltered. These findings suggest that kappa-bungarotoxin may be used as a selective pharmacological tool for the study of nicotine actions which are dependent on ganglionic-like receptors, which have been associated with Purkinje cells in previous studies.
Action Potentials↗
Sensory gating in schizophrenics and normal controls: effects of changing stimulation interval.
Auditory evoked potentials were recorded using a paired click, conditioning-testing paradigm in 10 schizophrenics and in 10 normal subjects with no family history of psychotic disorder. The paradigm is used to demonstrate central nervous system gating of responsiveness to auditory stimuli by examining the extent to which the response to the conditioning stimulus diminishes the response to a test stimulus occurring a short time later. Recordings were made at conditioning-testing intervals of 500 msec, 150 msec, and 75 msec to determine subjects' gating of responsiveness to stimuli repeated at various intervals. The schizophrenics had conditioning-testing ratios indicative of poor gating of the auditory P50 wave at the 500-msec and 150-msec intervals, but most patients had good sensory gating at the 75-msec interval. Normal subjects showed good sensory gating at all three intervals. Results suggest that although sensory gating mechanisms responsible for changes in neuronal response at longer intervals are chronically defective in schizophrenics, other gating mechanisms functioning at shorter intervals appear to be intact and function well in most patients. The results may lead to increased specification of the neurobiological basis of sensory abnormalities in schizophrenia.
Adult↗
Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson's disease. A detailed account of methodology and a 6-month follow-up.
By using stereotaxic surgical techniques, ventral mesencephalic tissues from aborted human fetuses of 8 to 10 weeks' gestational age were implanted unilaterally into the striata in two patients with advanced Parkinson's disease. The patients were treated with a cyclosporine, azathioprine, and steroid regimen to minimize the risk for graft rejection. They were examined for 6 months preoperatively and 6 months postoperatively and continued to receive the same doses of antiparkinsonian medication. There were no significant postoperative complications. No major therapeutic effect from the operation was observed. However, in the clinical tests, both patients showed small but significant increases of movement speed for repeated pronation-supination, fist clenching, and foot lifting. The rate of walking also increased in the one patient tested. For both patients, there was an initial worsening postoperatively, followed by improvement vs preoperative performance at 1 to 3 months. Both patients also showed significant improvement in the magnitude of response to a single dose of levodopa (L-dopa), but there was no increase in the duration of drug action. The motor readiness potential increased in both patients postoperatively, primarily over the operated hemisphere. Neurophysiological measurements also showed a more rapid performance of simple and complex arm and hand movements on the side contralateral to transplantation in one patient at 5 months postoperatively. Positron emission tomography demonstrated no increased uptake of 6-L-(18F)-fluorodopa in the transplanted striatum at 5 and 6 months. Taken together, these results suggest that the fetal nigral implants may have provided a modest improvement in motor function, consistent with the presence of small surviving grafts. Although our results support further scientific experimentation with transplantation in Parkinson's disease, widespread clinical trials with this procedure are probably not warranted at this time.
Contingent Negative Variation↗
Direct determination of unconjugated HVA in human plasma filtrates by HPLC coupled with dual-electrode coulometric electrochemical detection.
We report a procedure for the rapid determination of unconjugated homovanillic acid (HVA) in human plasma by cartridge filtration followed by direct injection into an isocratic HPLC system coupled with dual-electrode coulometric electrochemical detection. Sample preparation is rapid and more than 72 samples can be studied in 24 h using an automated HPLC system. The intra- and interassay precisions of the assay equal or exceed previously reported methods. While this methodology has been employed to study plasma free HVA, the concept of the technique may be applicable to other compounds, as well as different assay procedures, to greatly decrease sample preparation time.
Autoanalysis↗
Unconjugated methoxylated catecholamine metabolites in human saliva. Quantitation methodology and comparison with plasma levels.
A newly developed method for the simultaneous extraction and quantitation of the unconjugated levels of the catecholamine metabolites vanilmandelic acid (VMA), 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and homovanillic acid (HVA) in plasma by high performance liquid chromatography with electrochemical detection was modified and applied to studies of human saliva. The assay had a mean coefficient of variation under 3% for each of the metabolites. Levels of plasma VMA, MHPG and HVA were measured in 28 normal subjects and compared to their saliva levels, obtained before and after stimulation by mastication. Significant correlations were found between plasma and saliva MHPG and HVA, but there was no correlation between plasma and saliva VMA. Salivary MHPG and HVA can be reproducibly assayed and may be useful tools for indications of changes in central and peripheral catecholamine metabolism.
Catecholamines↗
Nicotine-induced inhibition of cerebellar Purkinje neurons: specific actions of nicotine and selective blockade by mecamylamine.
The specificity and pharmacological characteristics of the effects of local administration of nicotine on cerebellar Purkinje cells in the rat were examined electrophysiologically. Local application of nicotine, whether by pressure-ejection or by iontophoresis, depressed the spontaneous discharge of Purkinje neurons in a reversible and dose-dependent manner. This action could not be mimicked by local application of vehicle alone. The inhibitory effects of (-)-nicotine were several-fold more potent than that of the (+)-enantiomer. Systemic administration of the ganglion blocker mecamylamine reliably and reproducibly antagonized the nicotine-induced inhibitions of Purkinje cells whereas nicotine-induced excitation of interneurons was not altered. Local pressure-ejection of mecamylamine also antagonized the inhibitory actions of nicotine, administered by iontophoresis. Since the central effects of nicotine on behavior are stereospecific and sensitive to mecamylamine, the data in this study further support the hypothesis that the actions of nicotine on Purkinje neurons are mediated by ganglionic-like receptors. These findings also suggest that the Purkinje cell may serve as a good cellular model for studies on central pharmacology of nicotine.
Animals↗
Electrophysiological effects of locally applied noradrenergic agents at cerebellar Purkinje neurons: receptor specificity.
We have investigated the receptor subtype(s) mediating the noradrenergic inhibition of cerebellar Purkinje cell spontaneous firing rate using local application of specific agonists and antagonists, in situ, via pressure microejection. Extracellular action potentials were recorded from Purkinje neurons in anesthetized Fischer 344 rats. Timolol, a beta-receptor antagonist, did not affect norepinephrine (NE)-induced inhibition in 9 of 12 cells studied. Phentolamine, an alpha-receptor antagonist, blocked the effect of NE in 8 of 11 cells. To further determine the subtype of alpha-receptor involved, the effects of the alpha 1-antagonist prazosin and alpha 2-antagonists idazoxan and yohimbine were examined. While prazosin had no effect on NE-mediated inhibition, both idazoxan and yohimbine blocked NE effects. Idazoxan was also successful in blocking phencyclidine (PCP), an indirect noradrenergic agonist. The inhibitory action of NE upon Purkinje cell firing rate was mimicked by the selective alpha 2-agonist clonidine; this action of clonidine was blocked by idazoxan but not by timolol or prazosin. In addition, the alpha 1-adrenergic agonist phenylephrine and the beta-adrenergic agonist isoproterenol inhibited Purkinje cell firing rate. Phenylephrine effects were blocked by prazosin but not by timolol or idazoxan. Isoproterenol-induced inhibition was blocked by timolol but not phentolamine. Taken together, these studies suggest that both alpha- and beta-receptors alter Purkinje cell firing rate; the depressant action of locally applied NE, however, seems to be mediated primarily via an alpha 2-adrenergic receptor.
Action Potentials↗
Brain evoked potentials as predictors of risk.
Sensory evoked potentials are capable of demonstrating brain sensory and cognitive function. These measures of brain activity can be used to demonstrate genetic influences in alcoholism. Auditory evoked potentials have been used successfully to demonstrate inherited differences in alcohol sensitivity. As in animal models, these inherited differences are limited to particular neuronal mechanisms and are not a general property of all neurons. The P300 wave, which is elicited in particular paradigms in which the subject is required to attend to specific stimuli, is smaller in subjects who are at high risk for alcoholism by virtue of having an alcoholic father. These subjects at risk for alcoholism show lower P300 amplitudes in paradigms in which they are given small doses of alcohol. P300 is also small in younger high-risk subjects who have never been exposed to alcohol. The evoked potential data are in general agreement with earlier electroencephalographic data that suggested the presence of electrophysiological abnormalities in the children of alcoholics.
Adolescent↗
Increased central noradrenergic activity during benzodiazepine withdrawal: an electrophysiological study.
Spontaneous discharge rates of cerebellar Purkinje neurons were decreased in rats withdrawn from chronic treatment with alprazolam, diazepam, and lorazepam relative to discharge rates recorded from control rats. Prior treatment with 6-hydroxydopamine to deplete cerebellar levels of norepinephrine significantly reduced this effect of diazepam upon Purkinje cell firing rates. The data suggest that increased noradrenergic activity may be occurring during withdrawal from benzodiazepines.
Action Potentials↗
Reproducibility of the measurement of plasma noradrenergic and dopaminergic metabolites in normal subjects.
The object of this study was to determine the reproducibility of the measurement of plasma catecholamine metabolites in normal control subjects and to assess the influence of factors such as time of day, diet, activity, blood pressure, and mood on the variance of these measures. Plasma free homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and vanillylmandelic acid (VMA) were simultaneously measured by high performance liquid chromatography with electrochemical detection. Samples were collected from 15 doctors and nurses at 8 a.m. and at noon on 2 separate days. After the fasting 8 a.m. sample, the subjects ate a regular hospital breakfast. Activity in their usual tasks on an inpatient psychiatric unit was monitored electronically by an activity meter. Levels of each metabolite were not significantly different between days at the respective assay times and were highly correlated for individuals. MHPG showed a significant increase from morning to noon, while HVA showed a significant decrease. Activity, dietary intake of tyrosine and tyramine, blood pressure, pulse, scores on the Profile of Mood States, age, and sex were not related to plasma levels. The results demonstrate that measures of dopamine and norepinephrine metabolites have significant reliability in normal subjects in a setting used for research studies with psychiatric patients.
Adult↗
Age-related changes in cerebellar noradrenergic function.
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Aging↗
Education and fertility in two Chinese provinces: 1967-1970 to 1979-1982.
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Asia↗
The electrophysiological effects of nicotine in the rat cerebellum: evidence for direct postsynaptic actions.
The agonistic actions of nicotine in the cerebellum were dependent on the type of cerebellar neuron studied. Purkinje cells were inhibited and cerebellar interneurons were excited by pressure-ejected nicotine. The simultaneous iontophoresis of Mg2+ failed to block nicotine agonistic actions on either cell type. Since Mg2+ reduces presynaptic release of neurotransmitters, our findings suggest that the pharmacological actions of nicotine on cerebellar neurons are due to direct postsynaptic mechanisms.
Action Potentials↗