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Biomedical subjects

H S Singer

Publications and source records attributed to H S Singer.

At least 19 recordsLinked to original sources
PubMed1992

The validity of instruments measuring tic severity in Tourette's syndrome.

By using four different scales that measure tic severity in Tourette's syndrome, three independent judges concurrently evaluated their validity and interjudge reliability in 20 affected individuals. The Yale Global Tic Severity Scale, Tourette's Syndrome Severity Scale, Tourette's Syndrome-Clinical Global Impression Scale, and the Hopkins Motor and Vocal Tic Scale were equally effective in determining overall severity and showed good interrater reliability. Both historical information and direct observation of the subject were shown to have a significant contribution towards the overall assessment of tic severity. With all instruments, tic symptom ratings were shown to be independent of those for either attention-deficit hyperactivity disorder or obsessive-compulsive disorder. A 67% incidence of behavioral problems and social difficulties was identified by the Child Behavior Checklist. Nevertheless, associations with tic severity were limited to areas showing interference with social relationships and school adjustments. These results extend the understanding of Tourette's syndrome severity scales and provide additional information necessary for the development of a unified rating scale.

Adolescent↗
PubMed1992

Chronic recurrent headaches in children.

Chronic recurrent headaches in children can be classified into distinct categories based on a careful history and physical examination. Migraine and muscle contraction headaches are common in the pediatric population. Laboratory studies should be limited to those individuals who have other signs or symptoms accompanying headaches that raise concern. Reassurance about the underlying pathophysiology of vascular or muscle contraction headaches, their benign nature, and favorable prognosis may not only relieve associated anxiety that may produce or prolong headache, but also may relieve the headache itself. Symptomatic mild analgesics and behavioral medicine therapy are often sufficient, although occasionally prophylactic pharmacotherapy is required. The long-term prognosis for children with chronic recurrent headaches is generally favorable.

Age Factors↗
PubMed1991

Abnormal dopamine uptake sites in postmortem striatum from patients with Tourette's syndrome.

The dopamine hypothesis for Tourette's syndrome proposes that the disorder is pathologically related either to an excessive amount of dopamine or to supersensitive receptors. To evaluate these proposals, pre- and postsynaptic markers of dopamine metabolism were measured in postmortem striatum from three adults with the diagnosis of Tourette's syndrome. Neuronal dopamine uptake carrier sites [( 3H]mazindol binding) were significantly increased in number over control values by 37% in the caudate and by 50% in the putamen. High-pressure liquid chromatographic assays of dopamine and its primary metabolites, homovanillic acid and 3,4-dihydroxyphenylacetic acid, showed normal findings. D1 and D2 subtypes of dopaminergic receptors [( 3H]SCH 23390 and [3H]spiperone binding, respectively) showed only slight alterations, presumably due to treatment with neuroleptics. The concentration of adenosine 3',5'-monophosphate (cyclic AMP) in putamen was reduced by 23%. Our data support earlier proposals of a dopaminergic abnormality in TS, but suggest that the mechanism involves a significant alteration of uptake sites. We speculate that increases in carrier site binding indicate an enhanced dopamine innervation within the striatum.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Tourette syndrome and other tic disorders. Diagnosis, pathophysiology, and treatment.

In this report, we discuss the definition, characteristics, pathophysiology, and treatment of tic disorders with a major emphasis on Tourette syndrome. Although the diagnosis of a tic disorder depends on the presence of motor and/or phonic tic(s), patients with these problems also have a variety of co-morbid features including obsessive-compulsive symptoms, attention-deficit hyperactivity disorder, behavioral difficulties, and learning disabilities. Conservative estimates for Tourette syndrome suggest a prevalence rate of 0.1-1.0 per 1000. This syndrome is inherited in a sex-influenced autosomal dominant pattern with either chronic multiple tic disorder or obsessive-compulsive disorder as alternative phenotypes of the putative gene. Current evidence continues to support a pathophysiologic mechanism involving synaptic neurotransmission, with the dopaminergic system as a primary candidate. Therapeutically, it is essential to clarify whether a patient's problems are related to tics or associated behavioral difficulties. Pharmacotherapy for motor and phonic tics is strictly symptomatic and should be reserved for those with functionally disabling symptoms. A comprehensive individualized treatment program is often required in the care of individuals with tic disorders.

Behavior↗
PubMed1991

Postencephalitic acquired Tourette-like syndrome in a child.

We report a 6-year-old girl who developed a Tourette-like syndrome following presumed herpes encephalitis. This case suggests that tics can be acquired in childhood and may be associated with lesions involving basal ganglia or limbic circuitry.

Child↗
PubMed1990

The effect of aluminum on markers for synaptic neurotransmission, cyclic AMP, and neurofilaments in a neuroblastoma x glioma hybridoma (NG108-15).

The effects of the neurotoxin aluminum on markers of synaptic neurotransmission, adenosine 3',5'-monophosphate, and neurofilaments have been evaluated in a neuroblastoma x glioma hybridoma (NG108-15). Cells were exposed for 4 days to 2 mM aluminum lactate, a concentration that did not suppress growth. Compared to controls, the activity of choline acetyltransferase was significantly increased by 37% associated with an up-regulation in enzyme activity (Vmax). Muscarinic receptors, measured by [3H]QNB binding, were reduced by 41%. In contrast, the activities of acetylcholinesterase and glutamate decarboxylase were not significantly changed. Aluminum raised the level of cyclic AMP by 20%, although adenylate cyclase activity was unchanged. Small amounts of both phosphorylated and non-phosphorylated neurofilaments were detected in NG108-15 cells. Aluminum intoxication, however, did not alter the quantity, ultrastructure, or immunoreactivity of neurofilaments. Our results demonstrate the capability of aluminum to produce selected changes in cholinergic markers and levels of cyclic AMP in a rapidly dividing cell line.

Aluminum↗
PubMed1990

Tourette's syndrome: a neurochemical analysis of postmortem cortical brain tissue.

Postmortem frontal, temporal, and occipital regions of the brain from adult patients who had a diagnosis of Tourette's syndrome were analyzed for neurochemical alterations. In 3 of 4 TS-affected brains, the concentration of adenosine 3',5'-monophosphate (cyclic AMP) was reduced in all brain regions evaluated. This diminution in cyclic AMP was not associated with a significant change in the activity of the synthesizing enzyme, adenylate cyclase. No significant differences were identified for the neurotransmitter-synthesizing enzymes choline acetyltransferase and glutamate decarboxylase. Concentrations of dopamine, norepinephrine, and the serotonin metabolite 5-hydroxyindoleacetic acid were not altered. Postsynaptic receptor-binding activity for muscarinic cholinergic ([3H]quinuclidinyl benzilate) and beta receptors ([125I]iodocyanopindolol) showed no generalized impairment. It is suggested that symptoms of Tourette's syndrome might be related to an abnormality within a second messenger system.

Adult↗
PubMed1989

Compartment-specific changes in the density of choline and dopamine uptake sites and muscarinic and dopaminergic receptors during the development of the baboon striatum: a quantitative receptor autoradiographic study.

In the fetal and young primate neostriatum, cholinergic and dopaminergic markers show patches of high density surrounded by a lower-density matrix. In the adult, the same markers display the opposite pattern, a lower density in striosomes, surrounded by a higher-density matrix. In order to understand the developmental sequences leading to the adult compartmental organization of the primate neostriatum, a quantitative technique was used to study the ontogeny of pre- and postsynaptic components of cholinergic and dopaminergic neurons in baboon caudate nucleus and putamen. The development of specific uptake mechanisms for choline and dopamine and receptors was studied by means of quantitative autoradiography of the specific binding of [3H]-hemicholinium-3 [( 3H]-HC3) and [3H]-mazindol [( 3H]-MAZ) to the choline and dopamine uptake systems, respectively. [3H]-pirenzepine [( 3H]-PIR) was used to label M1 muscarinic receptors and [3H]-spiroperidol [( 3H]-SPI) was used to label striatal dopamine D2 receptors. Serial sections were used for each ligand to determine the precise anatomical relationships between the binding patterns of the different markers. Our aim was to determine whether the adult striosomal distribution of the binding sites studied was due to 1) a selective decrease in patch/striosomal binding density or 2) a selective increase in matrix binding density. Our studies show that a postnatal decrease in the density of [3H]-HC3 sites in the patch/striosomes and an increase in the matrix density of [3H]-MAZ sites are the primary, but not the sole, changes in the compartmental distribution of these sites leading to the adult striosomal organization of the striatal cholinergic and dopaminergic innervation. D2 receptors follow the general developmental pattern of [3H]-MAZ and [3H]-HC3, changing their density of distribution in both compartments during the developmental period examined. In addition, M1 muscarinic receptors already display their adult pattern in the newborn baboon striatum, and therefore represent one of the first neurochemical makers to adopt its mature organization.

Animals↗
PubMed1989

Canine GM2 gangliosidosis: morphological and biochemical analysis.

Beta-hexosaminidase activity and the effects of ganglioside storage on neuronal function were examined in a German shorthair pointer (GSHP) with progressive neurodegenerative signs. Morphologic evidence of neuronal storage and massive accumulation of GM2 ganglioside were present. Beta-hexosaminidase activity in plasma, liver, kidney, and brain, assayed with use of unsulfated fluorogenic substrates, was normal. There was no pathologic accumulation or aberrant localization of phosphorylated neurofilaments in neurons. Activity of cortical neurotransmitter synthesizing enzymes, choline acetyltransferase, and glutamate decarboxylase was unaffected. Ligand binding to carrier sites for choline high affinity uptake identified with [3H]hemicholinium-3 was increased, whereas post-synaptic binding to muscarinic cholinergic ([3H]QNB) and gamma-aminobutyric acid receptors ([3H]muscimol) was reduced.

Animals↗
PubMed1989

Nonketotic hyperglycinemia: studies in an atypical variant.

We diagnosed a 22-year-old man with psychomotor retardation, rare seizures, hyperglycinemia, and hyperglycinuria as an atypical variant of nonketotic hyperglycinemia (NKH). Despite this clinical phenotype and a CSF/plasma ratio confirming a mild variant, measurement of hepatic glycine cleavage activity and the P-protein component indicated the more severe neonatal variant.

Adult↗
PubMed1988

Development of beta 1 and beta 2 adrenergic receptors in baboon brain: an autoradiographic study using [125I]iodocyanopindolol.

[125I]iodocyanopindolol (ICYP) autoradiography was used to investigate the temporal development and distribution of beta 1 and beta 2 receptors in brains of baboons at ages embryonic day 100 (E100), full-term gestation (El80), and 3 years. In all brain regions examined, with the exception of the hippocampus, binding to beta 1 receptors exceeded that to beta 2 receptors. The highest densities of beta 1 receptors were found in the caudate nucleus, putamen, globus pallidus, substantia nigra, and cerebral cortex; intermediate receptor densities were observed in most nuclei of thalamus, and the lowest concentrations were in the hippocampus. At E100, beta receptors were identified in the striatum, globus pallidus, and thalamus. During maturation, the number of beta 1 receptors declined in cortical areas but increased in the head of the caudate and putamen. Significant differences in the developmental distribution of beta receptors during development were also detected: at E100 and E180 beta 1 receptors appeared as patches in the caudate and putamen, but by 3 years of age they were more homogeneously distributed in both regions; changes also occurred in the distribution of binding within cortical layers. Autoradiograms of [125I]ICYP and [3H]mazindol binding show overlapping patches of labeling in the E180 striatum, suggesting a possible developmental association between beta receptors and dopamine high-affinity uptake carrier sites. This study demonstrates that noradrenergic receptors in the primate forebrain undergo significant developmental reorganization with regional variations.

Aging↗
PubMed1988

The identification and characterization of a GABAergic system in the cholinergic neuroblastoma x glioma hybrid clone NG108-15.

gamma-Aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD) activity were identified and characterized in the cholinergic neuronal cell clone NG108-15. GAD activity is similar to form A in rat brain by being temperature sensitive and independent of pyridoxal 5'-phosphate in the assay mixture. Most of the NG108-15 GAD activity is inactivated by 1 mM amino-oxyacetic acid. In contrast to NG108-15 choline acetyltransferase, GAD activity is not enhanced when cells are grown with dibutyryl cyclic AMP. The GAD activity shows a cell-density dependent increase that does not correlate with changing level of endogenous GABA. The identification of GABAergic properties in the NG108-15 clone enhances its use as a neuronal model for studies of differentiation and neurotoxicity of drugs or chemicals.

Aminooxyacetic Acid↗
PubMed1988

Reductions in acetylcholine and nicotine binding in several degenerative diseases.

Alzheimer's disease, Parkinson's disease, and progressive supranuclear palsy are all characterized by loss of neurons in the basal forebrain cholinergic system and by associated reductions in cortical presynaptic cholinergic markers, such as choline acetyltransferase. In this report, we identify that a major cortical receptor alteration in these disorders is a reduction in nicotinic receptors measured using both tritiated acetylcholine and levorotatory tritiated nicotine binding.

Acetylcholine↗
PubMed1988

Effects of anticonvulsants on cholinergic and GABAergic properties in the neuronal cell clone NG108-15.

The effects of anticonvulsant drugs on growth, cholinergic, and GABAergic properties were examined in the neuronal cell clone NG108-15. Cells were exposed for 4 days to valproic acid, phenobarbital, phenytoin, or carbamazepine in concentrations equivalent to therapeutic free levels in human serum. Experiments were also performed with varying concentrations of a recently proposed antiepileptic, gamma-vinyl GABA. Of these five anticonvulsants, cell growth (total protein and cell counts) was decreased with valproic acid and phenytoin but only valproic acid and gamma-vinyl GABA altered neurotransmitter markers. Therapeutic concentrations of valproic acid increased choline acetyltransferase activity to 142% of control but had no effect on either the activity of glutamate decarboxylase or the level of GABA. The effects of a higher (toxic) concentration of valproic acid (200 micrograms/ml) were similar to those induced by the differentiating agent dibutyryl cyclic AMP: both decreased cell growth, enhanced the activity of choline acetyltransferase and reduced the activity of glutamate decarboxylase. Gamma-vinyl GABA had no effect on cholinergic markers but, at 1300 micrograms/ml, increased GABA levels to 135% of control despite the reduction of glutamate decarboxylase to 68% of control. In the NG108-15 cell clone, anticonvulsants have varying effects on cell growth, differentiation, and neurotransmitter systems. Our findings do not support the proposal that the mechanism of action for valproic acid, phenobarbital, phenytoin, and carbamazepine is via alteration of GABA levels.

Animals↗
PubMed1988

Eosinophilia of the cerebrospinal fluid: late reaction to a silastic shunt.

The differential diagnosis of CSF eosinophilia consists primarily of infection, infestation or malignancy. This report describes an eight-year-old patient with a ventriculoperitoneal shunt who presented with a two-year history of episodic headache and vomiting and persistent tenderness of the skin overlying the bulb of the shunt. Ventricular CSF showed persisting eosinophilia, but there was no evidence of infection or malignancy. All abnormalities resolved promptly after the shunt was replaced.

Child↗
PubMed1988

Saccades in Huntington's disease: slowing and dysmetria.

Eye movements were recorded from 20 mildly affected patients with Huntington's disease (HD) who were divided into two groups, 10 patients with onset of symptoms before age 30 and 10 with onset of symptoms after age 30. In the younger onset group (HD less than 30), peak saccade velocities were low (less than 255 deg/sec for 20-deg saccades) in six of the 10 patients, whereas none of the 10 patients in the older onset group (HD greater than 30) had peak saccade velocities lower than 300 deg/sec. Latencies for volitional saccades were greater than normal in the HD greater than 30 group, but were normal for the HD less than 30 group. The ability to maintain steady fixation in the face of a distracting visual stimulus was decreased, to the same degree, in both groups of HD patients. In addition, 70% of the HD less than 30 group had an affected father, while 70% of the HD greater than 30 group had an affected mother. These findings suggest that the pathophysiology of the slow saccades, initiation deficit, and excessive distractibility in HD are different.

Adolescent↗