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Biomedical subjects

R J Wyatt

Publications and source records attributed to R J Wyatt.

At least 19 recordsLinked to original sources
PubMed1992

gamma-Butyrolactone-sensitive and -insensitive dopamine release, and their relationship to dopamine metabolism in three rat brain regions.

Some data suggest dopamine (DA) release from neuronal terminals is partially independent of impulse flow. We examined the changes in tissue DA and its major metabolite levels 30 and 90 min after treatment with y-butyrolactone (750 mg/kg). Accumulation of 3-methoxytyramine within 10 min of pargyline injection (75 mg/kg) was used as an index of DA release. Thirty minutes after gamma-butyrolactone injection, DA content was increased maximally in the frontal cortex, nucleus accumbens and striatum (by 91%, 80% and 73%, respectively). 3-Methoxytyramine rates of accumulation were reduced by 77%, 77%, and 92%, respectively. Ninety minutes after the treatment, DA levels remained high in all three areas, while DA release was persistently low in the striatum and nucleus accumbens, but had returned to baseline in the frontal cortex. Changes in 3,4-dihydroxyphenyl-acetic acid and homovanillic acid levels were not synchronized with changes in DA release in the striatum and nucleus accumbens, and were absent in the frontal cortex. The data suggest that an impulse flow-independent mechanism contributes to approximately one tenth and one fourth of the basal DA release in the terminals of DA neurons originating in the substantia nigra and ventral tegmental area, respectively. The acidic DA metabolite levels become at best poorly associated with DA release during blockade of the DA neuronal firing, probably because of the increased in situ metabolism of newly synthesized DA.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Hydra head activator peptide has trophic activity for eukaryotic neurons.

The synthetic undecameric peptide, pGlu-Pro-Pro-Gly-Gly-Ser-Lys-Val-Ile-Leu-Phe, known as the hydra head activator peptide, present in high concentrations in mammalian hypothalamus and intestine, was tested for neurotrophic activity in a survival assay using cultured chick embryonic sympathetic and dorsal root ganglion cells, and for morphological differentiation activity on neuroblastoma cells. Hydra head activator peptide supported neuron survival. The optimal active concentration, 1 pM, was very similar to the concentration that causes bud and head formation in hydra. Maximal neuron survival obtained with hydra head activator peptide was close to that obtained with nerve growth factor: both substances enhanced survival up to 3 times that of control cultures. Bradykinin, which has some amino acid sequence homology with hydra head activator, was inactive as a neurotrophic factor. Hydra head activator induced rapid morphological differentiation of the mouse neuroblastoma cell line Neuro-2A. Neuro-2A responded to the peptide by process extension, 4 h after its addition to the culture medium. Neurotrophic factors isolated to date have been characterized by their ability to maintain cell viability and enhance neurite outgrowth. Hydra head activator peptide met these two criteria when tested in 3 different neuron culture systems. Our results suggest that the head activator peptide may act as a neurotrophic factor for neurons in other species, including mammals.

Amino Acid Sequence↗
PubMed1992

Search for cytomegalovirus in the postmortem brains of schizophrenic patients using the polymerase chain reaction.

Cytomegalovirus infection has a number of features that suggest a possible association between congenital infection and schizophrenia. Previous studies have investigated anticytomegalovirus antibody titers or attempted directly to identify viral antigens in body fluids or brain tissue from schizophrenic subjects but have been limited by the sensitivity of the available methods. The highly sensitive polymerase chain reaction, a newly developed technique for gene amplification, was used to search for cytomegalovirus in the DNA extracted from postmortem temporal cortex samples of eight schizophrenic subjects, eight nonschizophrenic suicide victims, and eight normal controls. Cytomegalovirus-specific DNA amplification was not detected in any of the samples. The implications of this finding for the viral hypothesis of schizophrenia are discussed.

Adult↗
PubMed1992

Blood-CSF barrier permeability and central nervous system immunoglobulin G in schizophrenia.

The ratio of albumin in cerebrospinal fluid (CSF) to serum may serve as an index of the integrity of the blood-CSF barrier, with increases in this ratio indicating increased permeability. The ratio of immunoglobulin G (IgG) in CSF to serum (divided by the albumin ratio to correct for variance in blood-CSF permeability) represents an index of the endogenous production of IgG in the central nervous system (CNS), with increases reflecting a possible infectious and/or autoimmune process stimulating central IgG synthesis. We analyzed simultaneously collected CSF and serum samples from 46 schizophrenic subjects, 8 of whom were studied both on and off neuroleptic treatment, and samples from 20 normal controls. The data indicated increases in CSF/serum albumin ratios or CSF/serum IgG indices in 22% and 20%, respectively, of the schizophrenic patients. Only 3 patients showed elevations in both indices. Comparison of values on and off neuroleptics indicated no significant effect of neuroleptics on these indices.

Adolescent↗
PubMed1992

Effects of chronic nicotine and haloperidol administration on muscarinic receptor-mediated phosphoinositide turnover in rat brain slices.

Muscarinic receptor-mediated phosphoinositide (PI) turnover in rat brain slices was assessed after chronic administration of nicotine (12 mg/kg/day) or haloperidol decanoate (1.5 mg/kg/day), either alone or in combination, for 6 weeks. Nicotine alone did not significantly alter carbachol-induced inositol monophosphate (IP1) accumulation in the frontal cortex, but did result in a significant increase in the hippocampus, and in a decrease in the striatum. Haloperidol alone attenuated carbachol-stimulated IP1 accumulation in all three brain regions. Chronic treatment with combined nicotine and haloperidol resulted in no significant change in carbachol-sensitive IP1 accumulation in either the frontal cortex or hippocampus but did result in a decrease in the striatum. The results suggest significant cross-talk between cholinergic and dopaminergic systems in affecting PI metabolism.

Animals↗
PubMed1992

Chronic lithium treatment prevents the dexamethasone-induced increase of brain polyamine metabolizing enzymes.

The paper describes the effects of various regimens of lithium chloride treatment on dexamethasone-induced increases in brain polyamine metabolizing enzymes. In contrast to peripheral tissues where acute lithium treatment suppresses the increase in ornithine decarboxylase activity, in the brain only chronic treatment was effective in preventing this increase and also the increases in the activities of S-adenosylmethionine decarboxylase and spermidine/spermine N1-acetyltransferase. This findings indicate a novel brain target for lithium's action and in turn provide new avenues for exploring polyamine function in the brain.

Acetyltransferases↗
PubMed1992

Polyamines modulate the binding of GABAA-benzodiazepine receptor ligands in membranes from the rat forebrain.

The effects of spermine, spermidine and putrescine on the binding of the GABAA-benzodiazepine receptor complex were examined in the hippocampus and frontal cortex membranes of the rat. The results demonstrated modulatory effects of polyamines on the binding of diazepam and flunitrazepam but not on that of GABA, muscimol and Ro 15-1788. When membranes were prepared without detergent, the polyamines enhanced the binding of diazepam. However, while the binding capacity increased after homogenization in the presence of the non-ionic detergent Triton X-100, the polyamines did not enhance the binding but inhibited the binding of diazepam and flunitrazepam at greater concentrations. Considered together with other studies, the present findings indicate that polyamines can modulate the binding characteristics of several different neurotransmitter receptor-ionophore complexes.

Animals↗
PubMed1992

Cerebrospinal fluid and serum levels of neuron-specific enolase in patients with schizophrenia.

Some patients with schizophrenia appear to have brain abnormalities, including enlarged third and lateral ventricles and reduced volumes of temporal lobe structures. These abnormalities could be attributed to a developmental abnormality or a neurodegenerative process. Neuron-specific enolase (NSE), a protein that is found primarily in neurons and neuroendocrine cells, has been used as an index of neuronal damage or degeneration. Levels of NSE in cerebrospinal fluid (CSF) and serum from 50 patients with acute and chronic schizophrenia were compared with those in normal and neurological control subjects. A double-antibody, solid phase iodinated radioimmunoassay was used to determine NSE levels. There was no evidence of elevated levels in patients with schizophrenia, whereas control subjects with neurological illnesses had increased levels of NSE in CSF. Because NSE is rapidly cleared from CSF, however, elevated levels could have been missed. Unmedicated patients tended to have lower levels than medicated patients.

Adult↗
PubMed1992

The transmission of vesicoureteral reflux from parent to child.

Vesicoureteral reflux is now recognized to be hereditary and familial. The incidence of reflux in siblings has proved to be significant but less is known about the incidence of reflux in the offspring of known reflux patients. In an ongoing prospective series of reflux screening we identified 23 patients of childbearing age with a known history of reflux and screened their 36 offspring with an awake voiding cystourethrogram. Of these 36 offspring 24 (66%) exhibited vesicoureteral reflux. The literature was also reviewed to determine the incidence of parent/child reflux from reported cases. This review revealed a 65% rate of reflux in the offspring of known patients. Our preliminary results coupled with those in the literature signify a need to screen the offspring of known reflux patients and suggest a rethinking of the genetic transmission for this trait. While vesicoureteral reflux could still be a multifactorial genetic trait with a major gene, consideration must also be given to an autosomal dominant inheritance pattern.

Child↗
PubMed1992

Search for evidence of herpes simplex virus, type 1, or varicella-zoster virus infection in postmortem brain tissue from schizophrenic patients.

The highly sensitive polymerase chain reaction (PCR) was used to search for herpes simplex virus type 1 (HSV-I) or varicella-zoster virus (VZV) in the DNA extracted from postmortem temporal cortex samples of 8 schizophrenic subjects, 8 nonschizophrenic suicide victims and 8 normal controls. HSV-I or VZV-specific DNA amplification was not detected in any of the samples studied.

Base Sequence↗
PubMed1992

Effect of chronic nicotine treatment and withdrawal on rat striatal D1 and D2 dopamine receptors.

The effects on rat striatal dopamine receptors after chronic nicotine administration (3 and 12 mg kg-1 day-1), and after withdrawal from chronic nicotine (12 mg kg-1 day-1), were studied. After 21 days of continuous minipump infusion, the control (saline) and nicotine-treated rats were killed. The nicotine-withdrawal rats were killed on day 28, 7 days after pump removal. Radioligand studies were performed to determine D1 ([3H]SCH23390) and D2 ([3H]spiperone) striatal dopamine receptor affinity (Kd) and maximum binding (Bmax). Dopamine inhibition of antagonist binding at 3 concentrations and the effect of 0.3 mM GTP on binding affinity were examined. No statistically significant differences between control and nicotine treatment or withdrawal groups were noted in either D1 or D2 receptor Kd or Bmax. Although nicotine has been shown to affect nigrostriatal dopamine release, chronic treatment does not appear to alter overall striatal dopaminergic receptor binding parameters.

Animals↗
PubMed1992

Treatment of tardive dyskinesia with vitamin E.

OBJECTIVE: Vitamin E (alpha-tocopherol), a free-radical scavenger, has been reported to improve symptoms of tardive dyskinesia. The authors attempted to replicate this finding under more controlled conditions in a larger study group. METHOD: Fifteen inpatients and six outpatients with tardive dyskinesia received up to 1600 IU/day of vitamin E for 6 weeks in a double-blind, placebo-controlled crossover study. Abnormal Involuntary Movement Scale (AIMS) examinations of these patients were videotaped and rated independently by two trained raters. Levels of neuroleptic medication and vitamin E were measured during both treatment periods. Eighteen patients who demonstrated high blood levels of vitamin E were included in the data analysis. RESULTS: Vitamin E levels were significantly higher while the patients were receiving vitamin E than while they were receiving placebo. For all 18 patients, there were no significant differences between AIMS scores after receiving vitamin E and AIMS scores after receiving placebo. In agreement with previous studies, however, the nine patients who had had tardive dyskinesia for 5 years or less had significantly lower AIMS scores after receiving vitamin E than after receiving placebo. There were no changes in neuroleptic levels during vitamin E treatment. CONCLUSIONS: Vitamin E had a minor beneficial effect on tardive dyskinesia ratings in a selected group of patients who had had tardive dyskinesia for 5 years or less. This effect was not due to an increase in blood levels of neuroleptic medications.

Adolescent↗
PubMed1992

Cerebrospinal fluid protein variations in common to Alzheimer's disease and schizophrenia.

Analysis of silver stained two-dimensional (2D) gels of cerebrospinal fluid (CSF) from 27 patients with schizophrenia (SCZ) and 10 patients with Alzheimer's disease (AD) revealed an increase in the relative amount of a polypeptide of 18,000M(r) and isoelectric point of 6.5 when compared to the appropriate controls. This protein was identified by its electrophoretic characteristics and by immune analysis of Western blots as an isoform of alpha-2 haptoglobin, provisionally identified as alpha-2FS haptoglobin. Alzheimer's disease versus control CSF samples showed a 6.8-fold increase in the percent mean density value of this haptoglobin isoform (n = 10 AD vs 11 control; P > 0.025) while a 4.4-fold increase was observed in the schizophrenic patients (n = 17 SCZ vs 10 control; P > 0.001). Two additional polypeptides (proteins '127' and '128') of 40,000 M(r) and isoelectric points 5.7 and 5.9, respectively, described previously by this laboratory, were found in the CSF of 27% of schizophrenics, 23% of the Alzheimer's disease patients, and 4% of the controls in the current study. The presence of proteins 127 and 128, as well as the increased concentrations of alpha-2 haptoglobin in the CSF of Alzheimer's disease and schizophrenic patients, may be useful as diagnostic biological markers. They may also indicate a common pathophysiology between these diseases.

Acute-Phase Proteins↗
PubMed1992

Creatine kinase and enolase: intracellular enzymes serving as markers of central nervous system damage in neuropsychiatric disorders.

A frequently used method to assess cellular dysfunction and damage in humans is to document the presence of uniquely intracellular proteins in extracellular spaces. Thus, increased plasma levels of transaminases generally reflect hepatocellular damage (Lieber 1978), increases in the cardiac fractions of creatine kinase (CK, or CPK for creatine phosphokinase) or lactate dehydrogenase (LDH) are diagnostic for myocardial infarction (Armstrong et al. 1979; 1982), and increases of skeletal muscle fractions of CK may indicate myopathy (Goto 1974; Ford 1984). Similarly, a number of enzymes and proteins serve as tumor markers in a variety of malignant cancer (e.g., Concannon et al. 1974; Foti et al. 1977).

Biomarkers↗
PubMed1992

Delayed L-phenylalanine infusion allows for simultaneous kinetic analysis and improved evaluation of specific-to-nonspecific fluorine-18-dopa uptake in brain.

The accumulation of 3-O-methyl-6-[18F]fluoro-L-DOPA (18F-30M-DOPA) in the brain from the circulation is responsible for most of the nonspecific background during 18F-DOPA positron emission tomography scanning. To increase the sensitivity of 18F-DOPA for imaging presynaptic dopamine systems, we took advantage of 18F-30M-DOPA's rapid clearance from the brain (T1/2 approximately 15-20 min). The infusion of the unlabeled amino acid L-phenylalanine, starting 75 min after 18F-DOPA administration, prevents 18F-30M-DOPA entrance into the brain through competition at the large amino acid transport system of the blood brain barrier. This method produces high specific-to-nonspecific contrast images of 18F accumulation beginning 15-30 min after onset of amino acid infusion and better sensitivity to small changes in 18F-DOPA uptake while still allowing for kinetic analysis of the data in the early time points. Kinetic and anatomical data were found to be strongly correlated.

Animals↗
PubMed1991

Tardive dyskinesia: neuropsychological, computerized tomographic, and psychiatric symptom findings.

Prior studies have suggested that schizophrenic patients with tardive dyskinesia (TD) have an unusual incidence of cognitive impairment, structural brain abnormalities, and negative symptoms. Twenty-seven schizophrenic patients with TD and an equal number of age-, gender-, and education-matched schizophrenic controls were studied. Each patient received neuropsychological testing, psychiatric symptom ratings, and most had cerebral computed tomography (CT) scans. Patients with TD significantly differed from controls on only 1 of 23, cognitive measures, and the overall group performance profiles were highly similar. No differences were observed on symptom ratings. Patients with TD had significantly smaller ventricular-brain ratios (VBRs) than controls. These data fail to support an association of TD with global measures of "organicity." Abnormal movements may result from specific dysfunction within the more purely motor circuits of the basal ganglia without compromising other neural systems involved in cognitive processing.

Adult↗