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Biomedical subjects

D M Sheppard

Publications and source records attributed to D M Sheppard.

At least 19 recordsLinked to original sources
PubMed2002

Abnormal line bisection judgements in children with Tourette's syndrome.

Tourette's syndrome (TS) has been associated with loss of normal basal ganglia asymmetry, as well as loss of normal functional asymmetry, including the leftward bias on traditional visuospatial tasks such as line bisection and turning bias tests. The aim of the present study was to examine the lateralisation of visuospatial attention in TS. We examined the effect of an irrelevant moving-dot background on line bisection judgements. Nine children with a DSM IV diagnosis of TS participated, in addition to 9 healthy controls, individually matched for age, sex and IQ. Horizontal lines of varying length were presented on a computer screen with either a blank background, or a moving, random-dot field. The dots moved either leftward or rightward across the screen at 40 or 80 mm/s, and participants were instructed to ignore these distracting stimuli when judging the lines. TS children were found to be abnormally right-biased in line bisection in a similar fashion to unmedicated ADHD children who, in a previous study, showed a similar small, yet significant, right-bias in line bisection. Matched controls showed a small, nonsignificant left bias, consistent with past research. Unlike previous findings with hemineglect patients, the irrelevant moving background had no effect on bisection performance for TS children or healthy controls. The present findings suggest a deficit in visuospatial attention consistent with the emerging picture of a lateralised dysfunction of frontostriatal circuitry in TS.

Adolescent↗
PubMed2000

The neurodevelopmental frontostriatal disorders: evolutionary adaptiveness and anomalous lateralization.

The frontostriatal system (dorsolateral prefrontal cortex, lateral orbitofrontal cortex, anterior cingulate, supplementary motor area, and associated basal-ganglia structures) is subject to a range of neurodevelopmental disorders: Tourette's syndrome (TS), obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), autism, and probably depression. The system is responsible for our adaptive responses (initiation, execution, or withholding) to environmental situations, and the above disorders, involving effectively excessive release or withholding of various types of response, are all a consequence of changes in specific frontostriatal regions. The disorders all have a genetic component, and their persistence in the genome indicates that their clinical manifestations may also be associated, perhaps in low levels in close relatives, with certain adaptive advantages in given situations. Thus autism is associated with computational careers, depression with literary creativity, SCZ with lateral thinking and the Odyssean personality, ADHD with an Ice-Age readiness to respond, OCD with a focused range of interests, and TS with competitive sports and jazz improvisation. The disorders are all highly comorbid, and which one predominantly manifests may depend on how the frontostriatal system happens to be compromised as a result of inherited genetic predispositions and environmental contingency. We review the adaptive nature of the various subclinical manifestations and the evidence for concomitant phenomena (possibly epiphenomena): alterations in structural, functional, and behavioral lateralization in each syndrome. Indeed it is not clear that altered lateralization in frontostriatal disorders of a neurodevelopmental origin generally has any adaptive significance; it may often simply serve as a marker for altered regulatory function of the frontostriatal system, alterations which in low genetic dosage or penetrance continue to play an adaptive role in clinically unaffected close relatives of probands, but which, in high dosage or penetrance in the probands themselves, are generally deleterious.

Adaptation, Physiological↗
PubMed2000

Movement sequencing in children with Tourette's syndrome and attention deficit hyperactivity disorder.

Little research has been conducted to examine sequential motor functioning of children with Tourette's syndrome (TS) and attention deficit hyperactivity disorder (ADHD). Movement sequencing performance for a group of 12 children with TS and 24 children with ADHD children (12 taking and 12 not taking stimulant medication) and matched control subjects was examined using a serial choice reaction time button-pressing procedure. Aspects of movement preparation and execution were measured for 10 sequential two-way choice points along a response board that extinguished the illuminated target buttons at certain specific times contingent on the previous button press or release. The level of advance information was systematically reduced to provide three levels of reduction of advance information, including no reduction, moderate reduction, and high reduction. Children with TS and ADHD (unmedicated) showed larger increases in down time, reflecting aspects of movement preparation, for the highest level of reduction of advance information than did their respective control groups. These deficits are suggestive of underlying frontostriatal dysfunction. Furthermore, the normalization of performance for children with ADHD taking stimulant medication assists in the confirmation of the validity of such a clinical diagnosis and seems to add to the clinical efficacy of this form of treatment, which has previously been associated with improvements for predominantly attentional and inhibitory symptoms of ADHD.

Analysis of Variance↗
PubMed1999

Tourette's and comorbid syndromes: obsessive compulsive and attention deficit hyperactivity disorder. A common etiology?

Tourette's syndrome (TS), a neuropsychiatric movement disorder that manifests itself in childhood, is often associated with comorbid symptomatology, such as obsessions, compulsions, hyperactivity, distractibility, and impulsivity. Epidemiological studies suggest that a substantial number of TS patients develop clinical levels of obsessive-compulsive disorder (OCD) and/or attention deficit hyperactivity disorder (ADHD). This review aims to provide an integrated account of the three disorders in terms of their comorbidity. Neuroimaging studies suggest that all three disorders involve neuropathology of the basal-ganglia thalamocortical (BGTC) pathways: TS in the sensorimotor and limbic BGTC circuits; OCD in the prefrontal and limbic BGTC pathways; and ADHD in the sensorimotor, orbitofrontal, and limbic BGTC circuits. The pattern of comorbidity and other evidence indicates that the TS gene(s) may be responsible for a spectrum of disorders, including OCD and ADHD, but also that the disorders OCD and ADHD can exist in their own right with their own etiologies.

Attention Deficit Disorder with Hyperactivity↗
PubMed1999

Effects of stimulant medication on the lateralisation of line bisection judgements of children with attention deficit hyperactivity disorder.

OBJECTIVES: Deficits in the maintenance of attention may underlie problems in attention deficit hyperactivity disorder (ADHD). Children with ADHD also show asymmetric attention deficits in traditional lateralisation and visuospatial orienting tasks, suggesting right hemispheric (and left hemispace) attentional disturbance. This study aimed to examine the lateralisation of selective attention in ADHD; specifically, the effect of a moving, random dot background, and stimulant medication in the line bisection task. METHODS: The performance of children with ADHD, on and off methylphenidate, was examined using a computerised horizontal line bisection task with moving and blank backgrounds. Twenty children with a DSM-IV diagnosis of ADHD participated with 20 controls, individually matched for age, sex, grade at school, and IQ. Twelve of the 20 children with ADHD were on stimulant medication at the time of testing. Horizontal lines of varying length were presented in the centre of a computer screen, with either a blank background, or a moving, random dot field. The random dots moved either leftward or rightward across the screen at either 40 mm/s or 80 mm/s. RESULTS: The children with ADHD off medication bisected lines significantly further to the right compared with controls, who showed a small leftward error. Methylphenidate normalised the performance of the children with ADHD for the task with the moving dots. CONCLUSIONS: These results support previous evidence for a right hemispheric hypoarousal theory of attentional dysfunction, and are consistent with the emerging picture of a lateralised dysfunction of frontostriatal circuitry in ADHD.

Analysis of Variance↗
PubMed1989

Translocation 1;7 in four cases of myeloid disorders.

A der(1)t(1;7)(p11;p11) was observed in bone marrow chromosome analyses of four patients with myeloproliferative disorders. Three patients had developed secondary leukemias or preleukemias following chemotherapeutic exposure, and one patient was diagnosed with M4 de novo.

Adult↗
PubMed1988

Karyotypic analysis of the human monoblastic cell line U937.

Karyotypes of three sublines of the human cell line U937 showed considerable variation, but all contained four consistent marker chromosomes (i.e., 3q-, 11q-, 16p+, and 17p- chromosomes). The 11q- chromosome appeared to be derived from either an interstitial deletion in bands 11q21-23 or from a translocation with an unidentified chromosome. The presence of this chromosome was of particular interest because rearrangements of chromosome #11 at band 11q23 are often associated with malignancies of the monocytic lineage. The possible significance of these findings is discussed.

Chromosome Aberrations↗
PubMed1987

Cytogenetic analysis of four human ovarian carcinoma cell lines.

Four cell lines derived from adenocarcinomas of the ovary, including three recently established cell lines, have been karyotyped. Chromosomes #1, #3, and #6 were found to be frequently involved in translocations with various other chromosomes, in agreement with results of other investigators, strongly implicating genes on these chromosomes in ovarian tumorigenesis.

Adenocarcinoma↗
PubMed1985

Karyotypic analysis and chromosome polymorphisms in four choriocarcinoma cell lines.

Four choriocarcinoma cell lines were karyotyped and examined for genetic homozygosity or heterozygosity using chromosomal polymorphisms. The BeWo, Jar, and ElFa lines had modal chromosomes in the hypertriploid range, while the DoSmi line was hypotetraploid. A number of chromosomal rearrangements were seen in all lines but there was no common rearrangement. The BeWo and Jar cell lines, derived from tumors following term births, were shown to be heterozygous by the presence of both X and Y chromosomes. The ElFa and DoSmi lines, established following molar pregnancies, were shown to be heterozygous; the ElFa line by the presence of both X and Y chromosomes and the DoSmi line by the examination of Q-band polymorphisms. Thus, all four lines, whatever their origin, were shown to be genetically heterozygous.

Cell Line↗
PubMed1985

Localization of the oncogene c-erbA1 immediately proximal to the acute promyelocytic leukaemia breakpoint on chromosome 17.

Using in situ hybridization, c-erbA1 has been mapped immediately distal to the translocation breakpoint on chromosome 17 in fibroblasts with a karyotype 46,XX, t(15;17)(q22;q11). Previous work has shown that c-erbA1 is proximal to the translocation breakpoint on chromosome 17 in the t(15;17)(q22;q12-21) in acute promyelocytic leukaemia. The oncogene can therefore be localized to the region of chromosome 17 between the breakpoints in 17q11 and 17q12-21.

Chromosome Banding↗
PubMed1984

Two patients with complete hydatidiform mole with 46,XY karyotype.

In a study to correlate the genetic origin of hydatidiform moles with the subsequent fate of the patients, 62 complete moles were examined for cytogenetic and/or biochemical polymorphisms. Comparisons of polymorphisms in molar tissue with those seen in white blood cells from the parents have shown that the majority of complete hydatidiform moles are androgenetic in origin and homozygous for all polymorphisms examined. Where karyotyped, these moles were found to be 46,XX. Three exceptions were found in which the molar tissue was heterozygous for enzyme polymorphisms. Cytogenetic analysis of two of these cases confirmed heterozygosity and also revealed a 46,XY karyotype which was androgenetic in origin, most likely arising by dispermy. The two patients with 46,XY complete moles have been followed up for a minimum of 9 months and neither has required treatment for persistent trophoblastic disease.

Adult↗
PubMed1983

Purification of uroporphyrinogen decarboxylase from human erythrocytes. Immunochemical evidence for a single protein with decarboxylase activity in human erythrocytes and liver.

Uroporphyrinogen decarboxylase (EC 4.1.1.37) has been purified 4419-fold to a specific activity of 58.3 nmol of coproporphyrinogen III formed/min per mg of protein (with pentacarboxyporphyrinogen III as substrate) from human erythrocytes by adsorption to DEAE-cellulose, (NH4)2SO4 fractionation, gel filtration, phenyl-Sepharose chromatography and polyacrylamide-gel electrophoresis. Progressive loss of activity towards uroporphyrinogens I and III occurred during purification. Experiments employing immunoprecipitation, immunoelectrophoresis and titration with solid-phase antibody indicated that all the uroporphyrinogen decarboxylase activity of human erythrocytes resides in one protein, and that the substrate specificity of this protein had changed during purification. The purified enzyme had a minimum mol.wt. of 39 500 on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. Gel filtration gave a mol.wt. of 58 000 for the native enzyme. Isoelectric focusing showed a single band with a pI of 4.60. Reaction with N-ethylmaleimide abolished both catalytic activity and immunoreactivity. Incubation with substrates or porphyrins prevented inactivation by N-ethylmaleimide. An antiserum raised against purified erythrocyte enzyme precipitated more than 90% of the uroporphyrinogen decarboxylase activity from human liver. Quantitative immunoprecipitation and crossed immunoelectrophoresis showed that the erythrocyte and liver enzymes are very similar but not identical. The differences observed may reflect secondary modification of enzyme structure by proteolysis or oxidation of thiol groups, rather than a difference in primary structure.

Carboxy-Lyases↗
PubMed1983

Immunoreactive uroporphyrinogen decarboxylase in porphyria cutanea tarda.

Immunoreactive uroporphyrinogen decarboxylase was measured by rocket immuno-electrophoresis in haemolysates from 7 unrelated patients with familial porphyria cutanea tarda (PCT), 6 patients with sporadic PCT, and 7 normal subjects. In all patients with familial PCT immunoreactive enzyme protein was decreased (51% of normal), to the same extent as catalytic activity (56% of normal), whereas in sporadic PCT both measurements were normal. These results show that familial PCT is commonly caused by a mutation which does not lead to the production of non-catalytic cross-reactive immunological material. Familial PCT can be distinguished from other types of PCT by a simple immunoelectrophoretic method that does not involve measurement of uroporphyrinogen decarboxylase activity and which is therefore likely to be suitable for routine diagnostic use.

Carboxy-Lyases↗
PubMed1982

Twin pregnancy with complete hydatidiform mole (46,XX) and fetus (46,XY): genetic origin proved by analysis of chromosome polymorphisms.

In a case of complete hydatidiform mole with fetus the genetic origins were defined by the use of chromosomal polymorphisms. The fetus had a normal 46,XY karyotype with evidence of the presence of both maternal and paternal chromosomes. The mole was 46,XX and of androgenetic origin. There was no evidence of a maternal contribution, and duplication of paternal chromosomes was shown. In such atypical molar pregnancies examining genetic polymorphisms yields much more information than do sex chromosome studies and karyotyping, particularly in confirming the diagnosis and defining the origin and aetiology of the condition.

Adult↗
PubMed1982

Tetraploid conceptus with three paternal contributions.

Cytogenetic and biochemical polymorphisms have been used to determine the origin of a tetraploid conceptus. Genetic polymorphisms were found in chromosomes 1, 6, 9, 15, 16, 22 and the sex chromosomes. The conceptus was found to have one maternal and three paternal contributions, indicating an origin other than a failure of cytokinesis at the first cleavage division of the zygote. The results presented are in favour of a trispermic origin of the conceptus.

Adult↗
PubMed1981

Studies on human phenylalanine Mono-oxygenase. I. Restricted expression.

Enzyme assays for phenylalanine mono-oxygenase have been performed on a variety of non-hepatic human cell types under varying conditions. The cell types studied were cultured fibroblasts, short-term lymphocyte cultures, long-term lymphoblastoid cultures, cultured amniotic fluid cells, hair roots and placental extracts. The cultured cells were assayed after growth under standard conditions and in the presence of a high concentration of substrate, a low concentration of end-product, added hydrocortisone or dexamethasone and under combinations of these conditions. In no instance was a significant enzyme activity obtained.

Amniotic Fluid↗
PubMed1980

Identification of two types of porphyria cutanea tarda by measurement of erythrocyte uroporphyrinogen decarboxylase.

1. Erythrocyte uroporphyrinogen decarboxylase activity has been measured in 27 patients with porphyria cutanea tarda, of whom 11 had a family history of overt porphyria cutanea tarda. 2. Eight patients from six families had erythrocyte uroporphyrinogen decarboxylase activities that were decreased to about half of control values. This decrease was shown by family studies to be inherited as an autosomal dominant characteristic. Two of these patients had no family history of overt porphyria cutanea tarda. 3. Nineteen patients had uroporphyrinogen decarboxylase activities close to or within the range found in 18 control subjects. Of these, five patients had a family history of porphyria cutanea tarda. 4. Inheritance of an autosomal dominant gene which decreases uroporphyrinogen decarboxylase activity in erythrocytes and liver is an uncommon cause of porphyria cutanea tarda and may not explain all cases of familial porphyria cutanea tarda. The hepatic enzyme defect in the common type of porphyria cutanea tarda, in which erythrocyte uroporphyrinogen decarboxylase activity is normal, may be caused either by inheritance of a gene whose effect is restricted to the liver or by gene whose effect is restricted to the liver or by chemicals that selectively inhibit the hepatic enzyme.

Adolescent↗