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Biomedical subjects

L Thal

Publications and source records attributed to L Thal.

27 records · Page 2Linked to original sources
PubMed1984

Dementia and motor neuron disease: morphometric, biochemical, and Golgi studies.

In three patients dementia without neurofibrillary tangles or Pick bodies antedated amyotrophy by several years. The motor neuron disorder in two patients was characterized by terminal bulbar symptoms; in one it was similar to classic amyotrophic lateral sclerosis. In two patients, quantitative studies of selected regions of the cortex using a computerized image analyzer disclosed, as in patients with senile dementia of Alzheimer type, a marked reduction in the number of neurons, especially those larger than 90 mu 2. The findings differed from those in Alzheimer dementia, however, in that the cells in the substantia innominata were not reduced and the levels of choline acetyltransferase and somatostatin-like immunoreactivity, determined in one patient, were within normal limits. A variable degree of sponginess of the upper layers of the cortex was attributed to attrition of pyramidal cell dendrites, observed in the one patient in whom Golgi study was successful. Because of severe degeneration of the substantia nigra in all three, the disease in these patients may represent a subset of motor neuron disease or a multisystem atrophy.

Alzheimer Disease↗
PubMed1982

Behavioral and biochemical aspects of neuroleptic-induced dopaminergic supersensitivity: studies with chronic clozapine and haloperidol.

Rats were chronically injected with saline, clozapine, or haloperidol and tested for alterations in dopamine (DA)-mediated behavior, DA receptor binding, and both acetylcholine (ACH) concentration and choline acetylase activity. Behaviorally, chronic haloperidol significantly enhanced apomorphine-induced chewing and sniffing stereotypies, associated with DA nigrostriatal activation, while clozapine selectively enhanced apomorphine locomotor activity and cage-floor crossing, behavior associated with DA mesolimbic activation. Biochemically, chronic haloperidol significantly enhanced 3H-spiroperidol binding in striatum and in mesolimbic loci (nucleus accumbens/olfactory tubercle) while chronic clozapine failed to produce such enhancement. Acute haloperidol induced an initial decrease in striatal ACH concentration followed by a return of ACH to normal levels within 1 week. There was no change in choline acetylase activity during the same time interval. These findings suggest that haloperidol may inhibit DA mechanisms in both the nigrostriatal may inhibit DA mechanisms in both the nigrostriatal and mesolimbic systems, but that the effect of clozapine on DA mechanisms may be specific to mesolimbic rather than striatal structures. At the same time, the lack of effect of clozapine on 3H-spiroperidol binding may indicate that behaviorally important changes in DA sensitivity can develop independent of changes in post-synaptic DA receptors. The pattern of cholinergic changes with chronic haloperidol suggests that the increase in striatal DA receptor number seen with chronic treatment re-establishes DA inhibition of cholinergic firing within the striatum.

Acetylcholine↗
PubMed1978

3H-Apomorphine interactions with dopamine receptors in calf brain.

3H-apomorphine binds to membranes from areas of the corpus striatum and limbic system of calf brain saturable and with a drug specificity indicating that it labels dopamine receptors. In terms of drug specificity, log-logit displacement curve slopes and number of binding sites, 3H-apomorphine interacts with receptors in a manner more like 3H-dopamine than 3H-haloperidol. These properties of 3H-apomorphine binding are those of an apparently "pure" agonist in contrast to the partial agonist effects of apomorphine upon the dopamine-sensitive adenylate cyclase.

Animals↗
PubMed1971

Effects of morphone on choline acetyltransferase levels in the caudate nucleus of the rat.

1. Choline acetyltransferase (choline-o-acetyltransferase 2.3.1.6.) concentrations were determined in the caudate nucleus, thalamus, and cortex of control and morphine treated rats. The enzyme was assayed using a modified radiochemical method on a number of selected days, one hour after the last injection of 30 mg/kg of morphine and also during the subsequent phase of abstinence from morphine.2. Significant lowering of choline acetyltransferase activity in the caudate nucleus area was found in two cases, one hour after the first dose of morphine and upon subsequent abstinence from morphine.3. The enzyme activity in the two other parts of the brain remained at the normal levels.4. The presence of endogenous inhibitors formed during morphine administration was excluded.5. The relationship of a possible effect of morphine on the tissue binding of the enzyme and the subsequent lowering of its activity was tested by homogenization of the caudate nucleus area in different media. The decrease in enzyme activity occurred in all extraction media one hour after morphine administration.6. Inhibitory effects of in vitro addition of morphine to caudate nucleus homogenate, obtained from normal and morphine treated rats, were found to occur only at very high concentrations of the drug, negating the possibility of direct inhibitory effects of morphine.7. These experiments suggest two possible causes of the observed effects, which can be responsible for the lowering of enzyme activity, and can be operative simultaneously: (1) a negative feedback mechanism of accumulated acetylcholine, occurring after the first dose of morphine, and (2) the possible changes in enzyme configuration produced by morphine treatment.

Acetylcholine↗
PubMedDate not supplied

Analysis of longitudinal data in an Alzheimer's disease clinical trial.

Evidence of delayed progression is the primary mechanism for demonstrating therapeutic efficacy in clinical trials in Alzheimer's disease. In the major trials of therapeutic treatment of AD, to date, measures based on clinical judgement and cognitive performance, instead of mortality, have been used as the primary response measures. There is good reason for this since the course of the disease is quite long, and AD trials designed around mortality would require either very large sample sizes or very long follow-up in order to have adequate power. However, the evaluation of progression in AD using clinical markers is subject to a number of challenges often found in longitudinal databases, for example, missing data, floor and ceiling effects and non-linearity. Unfortunately, few of these issues are being addressed in the typical analysis of progression data. This paper explores these analytic issues in the context of the recently completed Alzheimer's Disease Cooperative Study trial of vitamin E and Selegeline in moderate AD patients.

Aged↗
PubMedDate not supplied

Validity of the Quality of Well-Being Scale for persons with human immunodeficiency virus infection. HNRC Group. HIV Neurobehavioral Research Center.

To evaluate the validity of the Quality of Well-Being Scale (QWB) for studies of patients with human immunodeficiency virus (HIV) disease, 514 men were studied who were divided among four categories: Centers for Disease Control and Prevention (CDC) Group A (N = 272), CDC-B (N = 81), CDC-C (N = 47), and uninfected male controls (N = 114). The QWB and a variety of medical, neuropsychological, and biochemical measures were administered to all participants. When QWB scores were broken down by HIV group, the CDC-C group was significantly lower (.614) than the CDC-B (.679), CDC-A (.754), or control group (.801). The difference between Groups CDC-C and CDC-A was about .14 units of well-being, which suggests that individuals lose 1/7 equivalents of 1 well year of life for each year they are in Group CDC-C in comparison to the asymptomatic group (Group CDC-A). In comparison to the controls, this would equal a 1-year of life loss for each seven infected individuals. The QWB was shown to be significantly associated with CD4+ lymphocytes (p < .001), clinician ratings of neuropsychological impairment (p < .04), neurologists ratings of dysfunction (p < .001), and all subscales of the Profile of Mood States. Baseline QWB scores were significant prospective predictors of death over a median follow-up time of 30 months. Multivariate models demonstrated high covariation between predictors of QWB. It was concluded that the QWB is a significant correlate of biological, neuropsychological, neurological, psychiatric, and mortality outcomes for male HIV-infected patients.

AIDS Dementia Complex↗