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Biomedical subjects

M H Lewis

Publications and source records attributed to M H Lewis.

At least 127 records · Page 7Linked to original sources
PubMed1991

Associative processes in differentially reared rhesus monkeys (Macaca mulatta): blocking.

Nine isolate and 6 socially reared adult rhesus monkeys were examined in a standard blocking procedure. A tone was paired with a startle stimulus (US) during Phase 1. A tone-light compound CS was paired with a US during Phase 2. In Phase 3, the light was presented alone to test for blocking. Results showed that learning about the light was blocked in social controls, but not in isolates. These data suggest isolates processed information atypically, in that they developed an association to a redundant cue. A second group of isolates (n = 3) underwent the identical procedures. However, conditioned reactions to the tone were extinguished before testing. Test responding was significantly reduced in this group, that is, blocking was obtained. These data suggest the within-compound association developed during Phase 2 mediated the isolate blocking deficit. Together, these findings imply long-term intellectual consequences of early social impoverishment. Such deficits may be mediated by alterations in central dopamine systems.

Animals↗
PubMed1991

The female brindled mouse as a model of Menkes' disease: the relationship of fur pattern to behavioral and neurochemical abnormalities.

The brindled mottled mutant mouse, a model of Menkes' disease, has alterations in copper homeostasis which cause, among other sequelae, neuronal degeneration in selected areas of brain. This work examined the neurochemical changes at postnatal days (PND) 15, 30 and 60 in females heterozygous for the sex-linked brindled mutation. These data were compared to behavioral alterations and to fur coat color at these same time points. The brindled heterozygotic females had lower concentrations of norepinephrine (NE) in the cingulate cortex, and higher levels of dopamine or dopamine metabolites in the cingulate cortex, thalamus and hypothalamus across all ages, although the difference was greatest at PND 15. The brindled females were much less active than their normal littermates at PND 15, but the differences were no longer evident at PND 30 and 60. Mottling of the fur is believed to result from low tyrosinase activity caused by abnormalities in copper metabolism. The fur pattern and behavior of the brindled mice were highly correlated with NE levels in the cingulate cortex and thalamus. These data show that female brindled mice have neurochemical abnormalities similar to (if less severe than) the male hemizygotes, that these abnormalities are regionally specific, are most apparent prior to 30 days of age, and are linked to behavioral deficits. These data also show that the extent of such deficits can be predicted by a quantitative analysis of the fur pattern of these females.

Age Factors↗
PubMed1991

Social deprivation of infant rhesus monkeys alters the chemoarchitecture of the brain: I. Subcortical regions.

Rhesus monkeys (Macaca mulatta) reared during the first year of life without social contact develop persistent stereotyped movements, self-directed behaviors, and psychosocial abnormalities, but neurobiological mechanisms underlying the behaviors of socially deprived (SD) monkeys are unknown. Monkeys were reared in total social deprivation for the first 9 months of life; control monkeys were reared socially (SR) with mothers and peers. Subjects were killed at 19-24 yr of age. Because the behaviors of SD monkeys are reminiscent of changes in striatal or amygdalar function, we used immunocytochemistry for substance P (SP), leucine-enkephalin (LENK), somatostatin, calbindin, and tyrosine hydroxylase (TH) to evaluate qualitatively and quantitatively patterns of neurotransmitter marker immunoreactivity within subcortical regions. In SD monkeys, the chemoarchitecture of the striatum was altered. Neuronal cell bodies and processes immunoreactive for SP and LENK were depleted markedly in patch (striosome) and matrix regions of the caudate nucleus and putamen; the average density of SP-immunoreactive neurons was reduced 58% relative to SR monkeys. Calbindin and TH immunoreactivities were diminished in the matrix of caudate and putamen of SD monkeys. TH-immunoreactive neurons, but not cresyl violet-stained neurons, in the substantia nigra pars compacta were decreased (43%) in SD monkeys. Peptide-immunoreactive terminals were reduced in the globus pallidus and substantia nigra in SD monkeys. The nucleus accumbens was the least affected of striatal regions. Striatal somatostatin immunoreactivity wa qualitatively and quantitatively similar in SD and SR monkeys. Several regions, for example, bed nucleus of the stria terminalis, amygdala, and basal forebrain magnocellular complex, that were in the same sections and are enriched in these markers did not appear altered in SD monkeys, suggesting a regional specificity for vulnerability. The altered chemoarchitecture of some basal ganglia regions in adult monkeys that experienced social deprivation as infants suggests that the postnatal maturation of neurotransmitter phenotypes in some structures is influenced by social environment. Abnormal motor and psychosocial behaviors resulting from this form of social/sensory deprivation may result from alterations in peptidergic and dopaminergic systems within the basal ganglia.

Amygdala↗
PubMed1991

D1 and D2 dopamine receptors independently regulate spontaneous blink rate in the vervet monkey.

Previous studies have revealed the involvement of a dopaminergic link in the regulation of spontaneous eye blink rate in primates. Based on the effect of dopamine D2 receptor-selective drugs and the anecdotal failure of the partial D1 agonist, SKF 38393, to alter blink rate in monkeys, it was assumed that D1 dopamine receptors did not control blink rate. The recent availability of dihydrexidine, a full D1 agonist, prompted us to reevaluate the role of D1 and D2 receptors in the regulation of blink rate. African green monkeys (n = 5) were used in all studies. Dihydrexidine produced a rapid and dose-dependent (up to 1 mg/kg, i.m.) increase in blink rate. The elevation in blink rate elicited by 0.3 mg/kg dihydrexidine was completely reversed by prior administration of a specific D1 antagonist, SCH 23390 (0.01 mg/kg, i.m.), but was unaffected by prior administration of a specific D2 antagonist, remoxipride (1 mg/kg, i.m.). Treatment with the specific D2 agonist, (+)-4-propyl-9-hydroxynaphthoxazine, led to a rapid and dose-dependent (up to 0.01 mg/kg, i.m.) increase in blink rate. The raised blink rate produced by (+)-4-propyl-9-hydroxynaphthoxazine (0.001 mg/kg) was abolished by pretreatment with remoxipride, but was not influenced by pretreatment with SCH 23390. These data indicate that spontaneous blink rate in the primate can be regulated by both D1 and D2 dopamine receptors. Furthermore, the receptor subtypes appear to affect blink rate in the same direction, yet function independently. Measurement of blink rate may provide a noninvasive method to assess the potency and selectivity of dopamine agonists and antagonists in primates.

Animals↗
PubMed1991

Behavioral effects in the rat of dihydrexidine, a high-potency, full-efficacy D1 dopamine receptor agonist.

Dihydrexidine (trans-10,11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phena nthridine) was reported recently to be the first full efficacy, potent D1 receptor agonist, but one also having some potency for D2 receptors. This study reports the effects of dihydrexidine on behavior of the rat. In study 1, the dose-response relationships of dihydrexidine (0.3 to 30 mg/kg) to various behaviors were assessed using direct observations. The frequency of three behaviors (grooming, sniffing, and locomotion) was significantly increased by this drug. The dose-response curve for drug-induced grooming approximated an inverted U shape. Dihydrexidine increased locomotion at two of the higher doses (3 and 30 mg/kg), and increased sniffing at doses greater than or equal to 1.0 mg/kg. Other behavioral topographies, such as licking, gnawing, and rearing, were not systematically affected by drug administration. Also, there was no indication of convulsion in any dihydrexidine-treated rat. In study 2, rats were pretreated with either the selective D1 antagonist SCH23390 or the selective D2 antagonist remoxipride prior to receiving dihydrexidine. SCH23390 antagonized the effects of dihydrexidine on grooming, locomotion, and sniffing. Conversely, remoxipride blocked dihydrexidine-induced locomotion, but had no effect on dihydrexidine-induced grooming or sniffing. Numerous behaviors are believed to be mediated by the interactions of D1 and D2 receptors. These data indicate that dihydrexidine can be an important tool for characterizing both the behavioral actions of D1 receptors, and the nature of D1/D2 interactions in mammalian brain. In addition, its high potency and full efficacy at D1 receptors, coupled with its significant D2 properties, may provide specific utility in certain clinical situations.

Animals↗
PubMed1990

Long-term effects of early social isolation in Macaca mulatta: changes in dopamine receptor function following apomorphine challenge.

The hypothesis that early social isolation results in long-term alterations in dopamine receptor sensitivity was tested using older adult rhesus monkeys. Isolated and control monkeys were challenged with apomorphine (0.1 and 0.3 mg/kg), and the drug effects on spontaneous blink rate, stereotyped behavior, and self-injurious behavior were quantified using observational measures. Monoamine metabolites were quantified from cisternal CSF by HPLC-EC, prior to pharmacological challenge. Isolated and control monkeys did not differ in CSF concentrations of HVA, 5-HIAA, or MHPG. At the higher dose, apomorphine significantly increased the rate of blinking, the occurrence of whole-body stereotypies, and the intensity of stereotyped behavior (as measured by observer ratings) in isolated monkeys. The frequency of occurrence of self-injurious behavior was too low to allow for meaningful comparisons. These significant differences in response to apomorphine challenge support the hypothesis that long-term or permanent alterations in dopamine receptor sensitivity, as assessed by drug challenge, are a consequence of early social deprivation.

Animals↗
PubMed1990

Triadimefon, a triazole fungicide, induces stereotyped behavior and alters monoamine metabolism in rats.

Triadimefon, a triazole fungicide, has been observed to increase locomotion and induce stereotyped behavior in rodents. The present experiments designed to characterize the stereotyped behavior induced by triadimefon used a computer-supported observational method, and tested the hypothesis that these observed effects involved central dopaminergic systems. Adult male and female Sprague-Dawley rats were injected with triadimefon (0, 50, 100, and 200 mg/kg) in corn oil (2 ml/kg ip) 4 hr prior to behavioral assessment. The two lowest doses of triadimefon increased the frequency of locomotion and rearing, while the highest dose induced highly stereotyped behaviors, including backward locomotion, circling, and head weaving. Immediately after behavioral testing, the rats were sacrificed, and the striata and olfactory tubercles, terminal fields of the nigrostriatal and mesolimbic dopamine systems, respectively, were removed. Steady-state concentrations of the monoamines dopamine and serotonin and their metabolites were determined by HPLC-EC. In independent experiments, the direct effects of triadimefon on dopamine (D1 and D2) receptor binding and dopamine-sensitive adenylate cyclase activity were assessed in vitro using rat striata. Dopamine concentrations were increased in olfactory tubercles, but decreased in striatum. Concentrations of 5-hydroxyindoleacetic acid (the major metabolite of serotonin) were increased only in striatum, and only in animals treated with 200 mg/kg triadimefon. In vitro, triadimefon neither competed with D1 or D2 dopaminergic radioligands nor affected dopamine-stimulated adenylate cyclase activity. Together these behavioral and biochemical data lend support to the hypothesis that triadimefon may have actions similar to those produced by indirect-acting dopamine agonists.

Adenylyl Cyclases↗
PubMed1990

Eder Puestow dilatation of benign rectal stricture following anterior resection.

Benign anastomotic stricture following anterior resection can be difficult to manage when the stricture is proximal. The acceptable surgical options are either a redo low resection with its accompanying hazards or, alternatively, the formation of a permanent colostomy. Although dilatation of such strictures is possible by blind passage of metal bougies, the authors believe that this technique must be regarded as hazardous. A technique of dilatation is described that is usually reserved for esophageal stricture, namely, Eder Puestow dilatation over a guide wire inserted under direct vision. Although this technique may not be without risk, this readily available equipment may be valuable in making a further resection unnecessary.

Adenocarcinoma↗
PubMed1990

trans-10,11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine: a highly potent selective dopamine D1 full agonist.

trans-10,11-Dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phenan thridine (4a, dihydrexidine) has been found to be a highly potent and selective agonist of the dopamine D1 receptor in rat brain. Dihydrexidine had an EC50 of approximately 70 nM in activating dopamine-sensitive rat striatal adenylate cyclase and a maximal stimulation equal to or slightly greater than that produced by dopamine. Dihydrexidine had an IC50 of 12 nM in competing for [3H]SCH23390 (1a) binding sites in rat striatal homogenate, and of 120 nM versus [3H]spiperone. These data demonstrate that dihydroxidine has about ten-fold selectivity for D1/D2 receptors. More importantly, however, is the fact that dihydrexidine is a full agonist. Previously available agents, such as SKF38393 (1b), while being somewhat more selective for the D1 receptor, are only partial agonists. The isomeric cis-dihydroxybenzo[a]-phenanthridine neither stimulated cAMP synthesis nor inhibited the cAMP synthesis induced by dopamine. The cis isomer also lacked appreciable affinity for [3H]-1a binding sites. N-Methylation of the title compound decreased affinity for D1 sites about 7-8-fold and markedly decreased ability to stimulate adenylate cyclase. Addition of an N-n-propyl group reduced affinity for D1 sites by about 50-fold and essentially abolished the ability to stimulate adenylate cyclase. However, this latter derivative had twice the affinity of the D2-selective agonist quinpirole for the D2 receptor. The results are discussed in the context of a conceptual model for the agonist state of the D1 receptor.

Adenylyl Cyclases↗
PubMed1989

The effects of stereotyped behaviour on orienting and tonic cardiac activity.

The relationship of cardiac activity to stereotyped behaviour was studied in profoundly mentally retarded persons, using both inter-group comparisons. The first intra-group comparison involved examining the relative magnitude of an orienting response to an auditory stimulus during the occurrence or nonoccurrence of stereotyped body rocking. While no differences were found between periods of rocking and non-rocking when behavioural measures of orienting were used, smaller changes in post-tone heart rate were observed during periods of stereotyped rocking. A second intra-group comparison found that stereotyped behaviour was associated with a significant increase in heart rate but no change in heart rate variability when compared to periods of no stereotyped activity. Finally, using an inter-group comparison, individuals who displayed stereotyped body rocking exhibited higher tonic heart rates and lower heart rate variability during periods of no stereotyped behaviour than was observed in matched control subjects. This result suggests that stereotyped behaviour may be correlated with reduced vagal tone.

Acoustic Stimulation↗
PubMed1989

Immune correlates of stress and depression.

This paper reviews the evidence for alterations in immunity associated with depression and stressful events. The reviewed studies examine a variety of immune parameters (e.g., mitogen response, natural killer cell activity and number, T-cell, and T-cell subpopulations) in relation to depression and in relation to a number of stressful events (e.g., death of spouse, examinations). There is considerable variability in the findings of the available studies. However, the review finds considerable evidence for an association between a variety of stressful events and lowered immunity and between severe depression and lowered immunity. The clinical relevance of these psychoimmune relationships remains in question.

Depressive Disorder↗
PubMed1989

Unilateral digital ischaemia secondary to embolisation from subclavian atheroma.

Four cases of unilateral digital ischaemia in the upper limb secondary to embolisation from atheromatous plaques in the proximal subclavian artery are presented. Digital subtraction angiography or arch aortography were used to demonstrate the site of atheroma. In one case diagnostic delay resulted from failure to visualise the site of embolisation on the original aortogram and a repeat examination was necessary. Subclavian endarterectomy was undertaken in each case and irreversibly ischaemic digits were managed by local amputation in two cases. Direct surgery to remove the site of embolisation was preferred to bypass or transposition procedures. No further embolic episodes have been recorded with a follow-up of 6 months to 3 years. The important diagnostic features and options in surgical management of this syndrome are discussed.

Arteriosclerosis↗
PubMed1988

Hepatic hemodynamics after chronic obstruction of the biliary tract in the dog.

Hepatic blood flow was measured in 12 dogs before and two weeks after obstruction of the bile duct (BD) or sham operation, using the electromagnetic flowmeter technique. Eight dogs with obstructed BD revealed an 41 per cent decrease in total hepatic blood flow caused by an approximately equal percentage decrease in both hepatic arterial (HA) and portal venous (PV) flow, a decrease in arterial blood pressure, an increase in PV vascular resistance and little change in hepatic oxygen consumption. Four sham operated dogs showed minimal hemodynamic response. A dual mechanism for the hepatic hemodynamic consequences of chronic biliary obstruction is suggested: Decreased HA blood flow associated with diminished blood pressure and reduced PV blood flow resulting from raised intrahepatic PV vascular resistance.

Animals↗