Clinical and laboratory findings in referrals for mitochondrial DNA analysis.

Background: Increasingly, mutations of mitochondrial DNA (mtDNA) are being considered when investigating the aetiology of neurological diseases in childhood. However, they are often difficult to predict clinically.

Method: Mitochondrial DNA analysis was carried out on 190 children from 1992 to 1996.

Simplified neuropathological diagnosis of dementia with Lewy bodies.

Pathological criteria have recently been developed to differentiate those cases where Lewy bodies contribute to the dementing process. We applied consensus criteria to 20 cases with a pathological diagnosis of Alzheimer's disease (all demented) and/or Parkinson's disease (three without dementia) and eight controls. In addition, we applied the criteria to the different cortical layers to determine whether the site of the semiquantification affected the diagnosis.

The relationship between striatal dopamine receptor binding and cognitive performance in Huntington's disease.

Seventeen individuals at risk for Huntington's disease and five symptomatic patients, who had previously undergone [11C]SCH23390 and [11C]raclopride PET to assess in vivo levels of striatal dopamine D1 and D2 receptor binding, had neuropsychological assessment on a series of tests known to be sensitive to symptomatic Huntington's disease, including tests of verbal fluency, memory, attention and planning. Compared with age- and IQ-matched healthy volunteers, clinically symptomatic carriers of the Huntington's disease mutation were found to be impaired on tests of verbal fluency, spatial span, planning and sequence generation, as were clinically asymptomatic Huntington's disease mutation carriers. In asymptomatic individuals, both striatal dopamine receptor levels and cognitive performance were lower in subjects approaching their estimated age of onset.

Off-axis crustal thickness across and along the east pacific rise within the MELT area.

Wide-angle seismic data along the Mantle Electromagnetic and Tomography (MELT) arrays show that the thickness of 0.5- to 1. 5-million-year-old crust of the Nazca Plate is not resolvably different from that of the Pacific Plate, despite an asymmetry in depth and gravity across this portion of the East Pacific Rise.

Influence of vision on upper limb reaching movements in patients with cerebellar ataxia.

The effects of vision on spatial and temporal characteristics of free unrestrained reaching movements of the arm were examined in 17 patients with ataxic syndromes due to degenerative disease of the cerebellum and its connections. Subjects were required to reach out and touch a visually presented target either in the dark or with the target and their finger visible. Overall, patients had prolonged reaction times and their movements were performed slower than normal.

The development and role of the Read Codes.

Produced and maintained by Britain's National Health Service, the Read Codes are a comprehensive, controlled clinical vocabulary. Here's a look at how the codes evolved, their use in the NHS, and the continual process of aligning the system with the needs of its users.

Exercise before puberty may confer residual benefits in bone density in adulthood: studies in active prepubertal and retired female gymnasts.

Exercise during growth may contribute to the prevention of osteoporosis by increasing peak bone mineral density (BMD). However, exercise during puberty may be associated with primary amenorrhea and low peak BMD, while exercise after puberty may be associated with secondary amenorrhea and bone loss. As growth before puberty is relatively sex hormone independent, are the prepubertal years the time during which exercise results in higher BMD? Are any benefits retained in adulthood? We measured areal BMD (g/cm2) by dual-energy X-ray absorptiometry in 45 active prepubertal female gymnasts aged 10.

Characterization of 12 microsatellite loci of the human MHC in a panel of reference cell lines.

The human genome contains a large number of interspersed microsatellite repeats which exhibit a high degree of polymorphism and are inherited in a Mendelian fashion, making them extremely useful genetic markers. Several microsatellites have been described in the HLA region, but allele nomenclature, a set of broadly distributed controls, and typing methods have not been standardized, which has resulted in discrepant microsatellite data between laboratories. In this report we present a detailed protocol for genotyping microsatellites using a semi-automated fluorescence-based method.

Cortical control of movement in Huntington's disease. A PET activation study.

Regional cerebral blood flow was measured with H2(15)O PET in seven patients with choreic Huntington's disease and seven age-matched control subjects. Subjects were scanned at rest and when performing paced joystick movements, in freely chosen directions, with the dominant arm. During movement, the patients showed impaired activation of contralateral primary motor, medial premotor, bilateral parietal and bilateral prefrontal areas along with increased activation of bilateral insular areas.

11C-diprenorphine binding in Huntington's disease: a comparison of region of interest analysis with statistical parametric mapping.

We compare region of interest (ROI) analytical approaches with statistical parametric mapping (SPM) of 11C-diprenorphine positron emission tomography findings in five patients with Huntington's disease (HD) and nine age-matched controls. The ROI were placed on caudate, putamen, and an occipital reference area. Ratios of striatal-occipital uptake from averaged static images centered at 60 minutes showed a mean 20% reduction in caudate (P = 0.

A mitochondrial DNA tRNA(Val) point mutation associated with adult-onset Leigh syndrome.

Subacute necrotizing encephalomyelopathy (Leigh syndrome) is associated with a number of mitochondrial DNA (mtDNA) abnormalities. We studied a family with maternally inherited encephalomyelopathy. Two siblings developed adult-onset Leigh syndrome.

Depletion of mitochondrial DNA by ddC in untransformed human cell lines.

In order to study the interaction between the nuclear and mitochondrial genomes we have developed a non-transformed cell system. It is based upon the complete removal of mtDNA from fibroblasts by treatment with a nucleoside analogue, 2',3' dideoxycytidine (ddC). After exposure to ddC we were able to generate viable fibroblasts devoid of mtDNA and to successfully repopulate them with exogenous mitochondria.

Evaluation of four candidate genes encoding proteins of the dopamine pathway in familial and sporadic Parkinson's disease: evidence for association of a DRD2 allele.

We assessed the role of four candidate genes encoding proteins involved in dopaminergic transmission, the dopamine transporter (DAT), the dopamine receptor D2 (DRD2), and the main catabolic enzymes of dopamine, monoamine oxidase A (MAOA) and B (MAOB), through allelic association studies in a population of familial and sporadic Parkinson's disease (PD). Using intronic polymorphisms of the four candidate genes, we studied the allelic distributions of the polymorphic markers in 18 affected members, one patient was chosen randomly from each PD family; 60 sporadic PD and 60 healthy unrelated control subjects were matched for sex and for country of origin. All subjects were white.

Increased c-fos expression in the brain during experimental murine cerebral malaria: possible association with neurologic complications.

Cerebral expression of c-fos protein was studied by immunocytochemistry in murine cerebral malaria (CM) and malaria without cerebral involvement (non-CM). c-fos expression, low in the brains of uninfected mice, increased in frequency, intensity, and distribution during the course of fatal CM (e.g.

Spinal and cutaneous schwannomatosis is a variant form of type 2 neurofibromatosis: a clinical and molecular study.

Objective: To delineate the clinical phenotype, molecular basis, and implications for screening in patients and families with multiple schwannomas not generally involving the cranium.

Methods: As part of a United Kingdom clinical and genetic study of type 2 neurofibromatosis (NF2) patients and families with multiple schwannomas who do not fulfil diagnostic criteria for NF2 have been identified. The clinical phenotype was studied in the extended families and molecular analysis was carried out at the NF2 gene locus on chromosome 22.

The phenotypic manifestations of chromosome 17p11.2 duplication.

Clinical and electrophysiological investigations and nerve biopsies were carried out on 61 patients shown to have a chromosome 17p11.2 duplication (hereditary motor and sensory neuropathy-HMSN Ia). Of these, 50 showed a Charcot-Marie-Tooth (CMT) phenotype and eight could be classified as having the Roussy-Lévy syndrome.

Chronic alcohol consumption does not cause hippocampal neuron loss in humans.

High alcohol consumption for long periods of time causes significant hippocampal neurodegeneration in rodents. A single study using neuronal density measures has reported similar findings in humans. The present study aims to substantiate these findings in human alcoholics using unbiased stereological techniques.

Hereditary demyelinating neuropathy of infancy. A genetically complex syndrome.

Nine cases are described of a demyelinating peripheral neuropathy that had an onset in infancy. The clinical features conformed to those of type III hereditary motor and sensory neuropathy or Dejerine-Sottas disease. All showed a severe neurological deficit and had profoundly reduced nerve conduction velocities.

Cerebellar presentation of multiple system atrophy.

Early diagnosis of multiple-system atrophy (MSA) is important in patients presenting with late-onset cerebellar ataxia because it has a less favourable prognosis than other degenerative ataxic disorders. We report cerebellar presentation of MSA in a series of 16 patients, 3 of whom later developed parkinsonism. Two-thirds of them had early evidence of impaired postural reflexes with a history of recurrent falls.

Associative learning in patients with cerebellar ataxia.

It has been claimed that patients with cerebellar pathology are impaired at associative learning. Patients with cerebellar ataxia (n = 7) were taught a visual-motor associative task. The task was chosen so as to allow comparisons with data currently being collected on the effects of cerebellar lesions on associative learning in monkeys.

Anticipation in familial Parkinson's disease: a reanalysis of 13 United Kingdom kindreds.

Several authors reported anticipation for age at onset in familial Parkinson's disease (PD) and postulated the involvement of an unstable trinucleotide repeat gene. We reanalyzed 13 previously reported multiple generation kindreds with familial PD to investigate anticipation and related biases. Although initial review of 33 informative parent-child and aunt/uncle-niece/nephew pairs revealed a mean anticipation interval of 9.

The gene for autosomal dominant cerebellar ataxia type II is located in a 5-cM region in 3p12-p13: genetic and physical mapping of the SCA7 locus.

Two families with autosomal dominant cerebellar ataxia with pigmentary macular dystrophy (ADCA type II) were investigated. Analysis of 23 parent-child couples demonstrated the existence of marked anticipation, greater in paternal than in maternal transmissions, with earlier age at onset and a more rapid clinical course in successive generations. Clinical analysis revealed the presence of a great variability in age at onset, initial symptom, and associated signs, confirming the characteristic clinical heterogeneity of ADCA type II.

Mitochondrial encephalopathy with multiple mitochondrial DNA deletions: a report of two families and two sporadic cases with unusual clinical and neuropathological features.

A mitochondrial myopathy associated with multiple deletions of mitochondrial DNA has been identified in pedigrees showing an autosomal dominant mode of inheritance. We report the first two British kindreds with this disorder, and two sporadic cases. The families exhibited some unusual clinical features, including pigmentary retinopathy and tremor; the latter was levodopa-responsive and associated with rigidity and micrographia in one family.