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Biomedical subjects

K L Davis

Publications and source records attributed to K L Davis.

At least 253 records · Page 14Linked to original sources
PubMed1986

Partial reversal of lesion-induced deficits in cortical cholinergic markers by nerve growth factor.

Nerve growth factor (NGF) was injected into the lateral ventricle (5 micrograms on 4 occasions) of rats which had previously sustained ibotenic acid-induced lesions of the nucleus basalis of Meynert. Lesioned, but vehicle-injected and sham-lesioned and vehicle-injected rats were run as controls. Infusion of NGF led to a significant recovery of cortical choline acetyltransferase and acetylcholinesterase activity 6 weeks, but not two weeks after the lesion.

Acetylcholinesterase↗
PubMed1986

Prostaglandin receptor sensitivity in psychiatric disorders.

The cyclic adenosine monophosphate (cAMP) responses to prostaglandin E1 (PGE1) in platelets and leukocytes from drug-free schizophrenic patients, depressive patients, and normal controls have been compared. Both schizophrenic and depressive patients had a significantly lower platelet cAMP response to PGE1 than controls. The platelet cAMP response to PGE1 did not discriminate among exacerbated, remitted, and poor-prognosis schizophrenic patients, or between exacerbated and remitted depressive patients. The cAMP response to PGE1 was negatively correlated with global symptom severity in actively ill schizophrenic patients, but was not correlated with symptom severity in exacerbated depressive patients. The leukocyte cAMP response to PGE1 did not differ among normal controls, schizophrenic patients, and depressive patients. These data indicate that a diminished platelet cAMP response to PGE1 may be a marker common to both schizophrenia and depression but that this effect does not extend to a cAMP-linked PGE1 receptor on another blood cell type.

Adult↗
PubMed1986

Adrenergic and serotonergic receptor responsiveness in depression.

Preliminary results are presented from a series of studies designed to characterize the regulation of release/metabolism and receptor responsiveness in the noradrenergic and serotonergic systems in acutely depressed patients and depressed patients in remission. Abnormal regulation of noradrenaline release/metabolism might be expected to be associated with the acute state of depression, while abnormalities of adrenoceptor responsiveness were hypothesized to persist in remission. Growth hormone responses to clonidine were measured as indices partially reflecting alpha 2-adrenoceptor responsiveness. Blunted responses to clonidine were found in both acutely depressed patients and patients in remission. The possible implications of these findings for the pathophysiology of the noradrenergic system in depression are discussed. Prolactin responses to the serotonergic agonist and serotonin-releasing agent fenfluramine were evaluated in acutely depressed patients, patients in remission and controls. A subset of the depressed patients appeared to have blunted prolactin responses to fenfluramine. However, very preliminary results do not show any difference in this response between patients who were acutely ill and those in remission, although the variability in both groups was great. These and related findings are discussed in terms of a possible contributory role of the serotonergic system in depression.

Clonidine↗
PubMed1986

Effect of apomorphine infusion on plasma homovanillic acid in normal subjects.

Previous experiments suggest that pharmacological perturbations of the brain dopaminergic system may be reflected by concentrations of plasma homovanillic acid. This study examined the ability of apomorphine infusion to reduce plasma homovanillic acid concentrations in normal subjects. The data suggests that apomorphine does not reduce plasma homovanillic acid concentration.

Adolescent↗
PubMed1986

Animal models of Alzheimer's disease: behavior, pharmacology, transplants.

Physostigmine, oxotremorine, RS-86, and a combination of piracetam and lecithin, have all been studied in patients with Alzheimer's disease. Intravenous physostigmine produced a significant improvement in patients' ability to recognize words and particularly to distinguish words they had never seen before from words previously presented. A subgroup of Alzheimer's patients had a clinically meaningful improvement to treatment with oral physostigmine, with the degree of improvement correlating with the ability of oral physostigmine to increase the nocturnal secretion of cortisol. No statistically significant differences of piracetam or piracetam and lecithin, compared to placebo were noted, however, the ratio of red cell to plasma choline might be associated with treatment responsivity. The potential therapeutic efficacy of oxotremorine proved all but impossible to assess due to concomitant adverse effects, particularly dysphoria. Results with another cholinergic agonist, RS-86, will be reported. This drug appeared to be better tolerated than oxotremorine. Animals with a kianic acid induced cortical depletion of choline acetyltransferase were found to have a significant impairment in retention of a passive avoidance task, an abnormality that was readily reversible by physostigmine, oxotremorine and 4-amino-pyridine. Cysteamine, a depletor of somatostatin, also produced a comparable deficit.

4-Aminopyridine↗
PubMed1986

Reliability of the family history method in genetic studies of Alzheimer's disease and related dementias.

The investigation of genetic and other causes of Alzheimer's disease requires reliable and valid methods of gathering historical data on elderly relatives. To assess the reliability of the family history method in the study of late-onset dementing illness, the authors studied families with Alzheimer's disease probands and control families. The results indicated that family history data obtained from multiple informants with standardized instruments are consistent across informants. The rate of Alzheimer's disease in the families studied was similar to rates found in previous studies.

Aged↗
PubMed1986

Cortisol and Alzheimer's disease, I: Basal studies.

Patients with Alzheimer's disease and nondemented elderly control subjects participated in studies of cortisol secretion during sleep and at 9:00 a.m. and were given dexamethasone suppression tests (DSTs) and lumbar punctures. Nocturnal and 9:00 a.m. cortisol concentrations were significantly higher in the demented patients. CSF MHPG negatively correlated with mean nocturnal cortisol. The most severely demented patients had the highest 9:00 a.m. and mean nocturnal cortisol concentrations. DST results did not distinguish samples with substantially different nocturnal cortisol concentrations. These results suggest that measurements of basal plasma cortisol concentrations and dexamethasone suppression provide different information but support the notion of somewhat higher than normal cortisol concentrations in Alzheimer's disease patients.

Aged↗
PubMed1986

Cortisol and Alzheimer's disease, II: Dexamethasone suppression, dementia severity, and affective symptoms.

The course of Alzheimer's disease can be complicated by depressive illness, often presenting enigmatically. To determine whether the dexamethasone suppression test (DST) can help distinguish patients with coexisting dementia and depression from those with dementia alone, DSTs were conducted with 22 nondepressed Alzheimer's disease patients. Eleven patients were nonsuppressors. The nonsuppressors were older than the suppressors but did not differ in depression or dementia ratings. The 8:00 a.m. postdexamethasone cortisol level correlated with depressive symptoms. A relationship between severity of dementia and depressive symptoms was also demonstrated.

Aged↗
PubMed1986

Correlates of lateral ventricular size in chronic schizophrenia, I: Behavioral and treatment response measures.

The ventricle-brain ratio (VBR) of 28 drug-free male schizophrenic inpatients was significantly higher than that of 21 matched normal control subjects and was not related to severity of positive or negative symptoms. Response to haloperidol in an open 6-week trial using a fixed-dose schedule was not predicted by severity of positive or negative symptoms or by VBR. The nine severely deteriorated patients with chronic "Kraepelinian" schizophrenia had left lateral ventricles 28% larger than their right, whereas the control subjects and other schizophrenic patients did not show ventricular asymmetry.

Adult↗
PubMed1986

Correlates of lateral ventricular size in chronic schizophrenia, II: biological measures.

CSF homovanillic acid levels showed a significant negative correlation with ventricle-brain ratios (VBRs) in a group of drug-free chronic schizophrenic male veterans, while CSF 5-hydroxyindoleacetic acid levels showed a similar, nearly significant trend. The response of plasma human growth hormone to 0.75 mg of apomorphine also demonstrated a significant negative correlation with VBR in this group, but other measures of central neurotransmitter activity were unrelated to ventricular size.

Adult↗
PubMed1986

Induction of interleukin 2 receptors on immature human thymocytes and co-expression of T3 and T6 antigens.

We have recently demonstrated that human thymocytes can be induced to express interleukin 2 (IL-2) receptors and to synthesize IL-2. The present study shows that relatively immature T6+ human thymocytes as well as the more mature T3+ thymocytes could be induced to express functional IL-2 receptors when activated with either Concanavalin A (Con A), Con A and 12-O-tetradecanoylphorbol 13-acetate (TPA) or IL-2 in combination with Con A or TPA. The phenotype of the common, immature thymocyte was identified by the binding of either fluorescein isothiocyanate (FITC)- or phycoerythrin (PE)-conjugated monoclonal anti-T6 (OKT 6) antibody and of mature thymocytes by the binding of monoclonal anti-T3 (OKT 3) antibody. We also observed that the expression of the T3 antigen on thymocytes, freshly isolated from thymic specimens obtained in the course of cardiac surgery of infants and children, was greater than 40% in 14 of 18 donors and that thymocytes co-expressed the T3 and the T6 antigen as determined by dual colour cytofluorometry. In thymocytes activated in vitro the expression of IL-2 receptors, determined by dual colour cytofluorometry with the PE-conjugated monoclonal anti-human IL-2 receptor antibody (PE anti-IL-2 R), was detected by the second day of induction in both immature T6+ and mature T3+ thymocytes. T6+ thymocytes proliferated in response to IL-2 and persisted in cultures for the duration of the study (18 days) and continued to express IL-2 receptors.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1985

Pharmacological alleviation of cholinergic lesion induced memory deficits in rats.

The cholinergic cells of the nucleus basalis of Meynert (nbM) have recently been found to degenerate in Alzheimer's disease and are thought to be at least partly responsible for the cognitive deficits which are characteristic of this disease. These experiments explored the behavioral effects of bilateral excitotoxic lesions of the nbM in adult rats. The first experiment showed that nbM lesions lead to a substantial deficit in the 24 hour retention of the habituation to a novel environment without affecting general exploratory behavior. The second experiment showed that this retention deficit is a general phenomenon reflected in the 72 hour retention of a one trial passive avoidance task. These retention deficits could be reversed by the postacquisition administration of the acetylcholinesterase inhibitor, physostigmine. These results support the hypothesis that central cholinergic systems are involved in the retention of learned responses, and suggest that cholinergic lesion induced retention deficits can be reversed by pharmacological means.

Alzheimer Disease↗
PubMed1985

Interaction of choline and scopolamine in human memory.

In a previous study (1), 8 gm. of oral choline given in a single dose were found to partially reverse the amnestic and subjective effects of 0.43 mg of scopolamine. The present study determined whether similar effects could be produced by 14 gm of choline given in 4 divided doses over 24 hrs and whether choline's effects in either study were related to plasma choline concentration. Ten normal subjects were given memory tests on three separate days, once after receiving 14 gm choline and 0.35 mg scopolamine (Ch-Sc), once following placebo and scopolamine (Pl-Sc), and once following placebo and placebo (Pl-Pl). Scopolamine markedly impaired memory performance but there was no difference between the Ch-Sc and Pl-Sc conditions. Plasma choline levels were significantly elevated in the Ch-Sc condition of both the single dose and divided dose studies. There was no difference in levels between studies nor were differences in memory performance correlated with elevations in plasma choline. These results indicate that any enhancement of cholinergic activity due to increased dietary choline is transient and of small magnitude.

Acetylcholine↗