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W Halliday

Publications and source records attributed to W Halliday.

16 recordsLinked to original sources
PubMed2000

AIDS- and non-AIDS-related PML association with distinct p53 polymorphism.

A population-based analysis of progressive multifocal leukoencephalopathy (PML) showed PML frequencies of 5.1% among patients with AIDS and 0.07% among patients with hematologic malignancies, but similar clinical features of PML in both groups. Sequencing of the p53 gene, exon 4, showed heterozygosity (Arg-Pro) at codon 72 in five of six PML patients. These findings indicate that frequencies of non-AIDS- and AIDS-related PML differ markedly but p53 polymorphisms may influence the occurrence of PML in both groups.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Induction of monocyte chemoattractant protein-1 in HIV-1 Tat-stimulated astrocytes and elevation in AIDS dementia.

Activated monocytes release a number of substances, including inflammatory cytokines and eicosanoids, that are highly toxic to cells of the central nervous system. Because monocytic infiltration of the central nervous system closely correlates with HIV-1-associated dementia, it has been suggested that monocyte-derived toxins mediate nervous system damage. In the present study, we show that the HIV-1 transactivator protein Tat significantly increases astrocytic expression and release of monocyte chemoattractant protein-1 (MCP-1). Astrocytic release of beta-chemokines, which are relatively less selective for monocytes, including RANTES, macrophage inflammatory protein-1alpha, and macrophage inflammatory protein-1beta, was not observed. We also show that MCP-1 is expressed in the brains of patients with HIV-1-associated dementia and that, of the beta-chemokines tested, only MCP-1 could be detected in the cerebrospinal fluid of patients with this condition. Together, these data provide a potential link between the presence of HIV-1 in the brain and the monocytic infiltration that may substantially contribute to dementia.

AIDS Dementia Complex↗
PubMed1997

Limb girdle muscular dystrophy in Manitoba Hutterites does not map to any of the known LGMD loci.

Limb girdle muscular dystrophy (LGMD) is a heterogeneous group of disorders affecting primarily the shoulder and pelvic girdles. Autosomal dominant and recessive forms have been identified; 8 have been mapped and 1 more has been postulated on the basis of exclusion of linkage. An autosomal recessive muscular dystrophy was first described in 1976 in the Hutterite Brethren, a North American genetic and religious isolate [Shokeir and Kobrinsky, 1976; Clin Genet 9:197-202]. In this report, we discuss the results of linkage analysis in 4 related Manitoba Hutterite sibships with 21 patients affected with a mild autosomal recessive form of LGMD. Because of the difficulties in assigning a phenotype in some asymptomatic individuals, stringent criteria for the affected phenotype were employed. As a result, 7 asymptomatic relatives with only mildly elevated CK levels were assigned an unknown phenotype to prevent their possible misclassification. Two-point linkage analysis of the disease locus against markers linked to 7 of the known LGMD loci and 3 other candidate genes yielded lod scores of < or = -2 at theta = 0.01 in all cases and in most cases at theta = 0.05. This suggests that there is at least 1 additional locus for LGMD.

Adolescent↗
PubMed1997

AIDS dementia complex with generalized myoclonus.

Focal and segmental, but not generalized, myoclonus have been described with human immunodeficiency virus (HIV) infection. We describe three patients with generalized myoclonus and acquired immunodeficiency syndrome (AIDS) dementia complex. In each, myoclonus persisted until death, invariably after a course of a few months. In two patients, myoclonus was elicited by sudden auditory stimuli and resembled a startle response. This form of myoclonus may be subcortical in origin. We suggest that the AIDS dementia complex be included among the causes of myoclonic dementia.

AIDS Dementia Complex↗
PubMed1996

Limb-girdle muscular dystrophy and Miyoshi myopathy in an aboriginal Canadian kindred map to LGMD2B and segregate with the same haplotype.

We report the results of our investigations of a large, inbred, aboriginal Canadian kindred with nine muscular dystrophy patients. The ancestry of all but two of the carrier parents could be traced to a founder couple, seven generations back. Seven patients presented with proximal myopathy consistent with limb girdle-type muscular dystrophy (LGMD), whereas two patients manifested predominantly distal wasting and weakness consistent with Miyoshi myopathy (distal autosomal recessive muscular dystrophy) (MM). Age at onset of symptoms, degree of creatine kinase elevation, and muscle histology were similar in both phenotypes. Segregation of LGMD/MM is consistent with autosomal recessive inheritance, and the putative locus is significantly linked (LOD scores >3.0) to six marker loci that span the region of the LGMD2B locus on chromosome 2p. Our initial hypothesis that the affected patients would all be homozygous by descent for microsatellite markers surrounding the disease locus was rejected. Rather, two different core haplotypes, encompassing a 4-cM region spanned by D2S291-D2S145-D2S286, segregated with the disease, indicating that there are two mutant alleles of independent origin in this kindred. There was no association, however, between the two different haplotypes and clinical variability; they do not distinguish between the LGMD and MM phenotypes. Thus, we conclude that LGMD and MM in our population are caused by the same mutation in LGMD2B and that additional factors, both genetic and nongenetic, must contribute to the clinical phenotype.

Adolescent↗
PubMed1995

The nosology of Hallervorden-spatz disease.

The development of magnetic resonance imaging has increased the number of clinical and pathological reports of Hallervorden-Spatz disease and Hallervorden-Spatz syndrome. The case-to-case variability is considerable. However, if gene loci and basic pathogenetic mechanisms are to be appreciated, it is imperative that like cases be compared and studied. The designation Hallervorden-Spatz disease should be reserved for the pediatric neurodegenerative disorder, recognizing that it occurs either as a familial or a sporadic disorder. The diagnosis of Hallervorden-Spatz syndrome is non-specific and encompasses a number of distinctive disorders, each having the pallidal triad of iron deposition, axonal spheroids, and gliosis. Clinically or pathologically distinct groups include (a) female patients with dementia, quadriparesis, and neurofibrillary tangles; (b) cases with Lewy bodies; and (c) cases with or without lipid abnormalities which have acanthocytosis and pigmentary retinal degeneration. Adult-onset cases are quite variable, both clinically and pathologically. Iron deposition in the globus pallidus separates these disorders from others in which axonal spheroids occur. Undoubtedly, the pallidal changes are related, some being primary and other possibly epiphenomena. Pathogenetic insights can only be achieved by investigating and comparing like cases.

Adult↗
PubMed1994

1H MRS of high grade astrocytomas: mobile lipid accumulation in necrotic tissue.

Sixty-four samples from six grade 4 astrocytomas were investigated ex vivo by 1H MRS at 360 MHz and subsequently by histopathology to obtain percentages of viable and necrotic tumour and grey and white matter. MR-visible lipids were detected in 87% of tumour samples. Necrotic foci were < 3 x 3 x 6 mm3. The means of the intensities/unit weight tissue of the lipid resonances at 5.33, 2.80, 1.29 and 0.89 ppm were significantly higher (p < 0.05) for three sets of comparisons: samples with 85-100% vs 50-75%; with 50-75% vs 10-40% and with 10-40% vs 0-5% necrosis. For the lipid resonance at 2.04 ppm the difference in the means was significant only for samples with 50-75% compared to those with 85-100% necrosis, because for samples with < 50% necrosis resonances from glutamine and possibly small amounts of glutamate, gamma-aminobutyrate and N-acetylaspartate anions contribute significantly to the spectral area at 2.0 ppm. We conclude that necrotic foci below MRI resolution yield the resonances at 1.3 and 0.9 ppm, and contribute to the intense resonance at 2.0 ppm observed in in vivo 1H spectra of some high grade astrocytomas.

Astrocytoma↗
PubMed1994

Mobile lipids and metabolic heterogeneity of brain tumours as detectable by ex vivo 1H MR spectroscopy.

To examine metabolic heterogeneity in primary brain tumour, multiple biopsies (one to five per tumour) from four benign meningiomas, five acoustic schwannomas, eleven glial tumours and five medulloblastomas were each subdivided into one to five samples (total = 194) and investigated using ex vivo 360 MHz 1H MR spectroscopy with histopathological correlation. Low amounts of mobile lipids were detected in meningothelial meningiomas and medulloblastomas, high amounts in some or all samples of all other tumours. The differences in non-lipid metabolites between different tumour types were less marked, with the exception of the medulloblastomas, which had high amounts of N-acetyl aspartate and cholines. The amount of mobile lipid correlated with Antoni type B areas in schwannomas and necrosis in a high grade giant cell tumour. The amount of lipid varied significantly from sample to sample in a grade 2 astrocytoma and grade 4 astrocytoma samples with 0-5% necrosis but did not correlate with the site in the tumour or histopathological characteristics. The metabolic heterogeneity occurred on a spatial scale at least as small as the size of the MR samples, i.e., < or = 60 mg. These results suggest that the detection of metabolic heterogeneity and mobile lipids may have importance for the design of clinical studies.

Astrocytoma↗
PubMed1992

Congenital hydrocephalus secondary to Walker-Warburg syndrome identified on the Manitoba Neonatal Screening Programme for Duchenne muscular dystrophy.

This report describes our first experience with a clinically important true false positive neonatal screening test for Duchenne muscular dystrophy (DMD). Neonatal screening for DMD began as a pilot programme in Manitoba on 1 January 1986 by analysis of creatine kinase (CK) activity in dried filter paper blood spots. To date, all except two males with positive initial and follow up neonatal CK screening tests were subsequently diagnosed as having DMD. Of these two, one was a newborn male with congenital hydrocephalus whose positive DMD screening test led to the identification of an associated congenital myopathy and confirmation of the diagnosis of Walker-Warburg syndrome.

Biopsy↗
PubMed1991

Three years' experience with neonatal screening for Duchenne/Becker muscular dystrophy: gene analysis, gene expression, and phenotype prediction.

Neonatal screening for Duchenne/Becker Muscular dystrophy (DMD/BMD) was begun as a pilot program on January 1, 1986. The aim of this program was to reduce the incidence of this X-linked recessive degenerative neuromuscular disease. The neonatal detection of a boy with DMD allows early identification of carriers and genetic counselling. This may avert the birth of other affected males born prior to clinical diagnosis of DMD in the propositus at about age 5 years. Between January 1, 1986, and December 31, 1988, we identified and characterized a cohort of 8 asymptomatic infant boys with grossly elevated levels of creatine kinase, an active primary dystrophic process of muscle and complete dystrophin deficiency. Five of 8 males have detectable DNA alterations involving the DMD/BMD locus. Based on current hypotheses, characterization of dystrophin expression of this cohort allows us to predict a DMD phenotype in all 8 boys. To date, no additional males with DMD have been born in these families. Prospective follow-up will allow us to test the validity of dystrophin testing in predicting the clinical course and impact of this program on reproductive decision making in these families.

Cohort Studies↗
PubMed1990

Meningiomas mimicking cerebral schwannoma.

A brain tumor with histological features reminiscent of schwannoma with underlying meningioangiomatosis was subjected to electron microscopic and immunohistochemical analysis, which confirmed the neoplasm as a meningioma. This prompted reexamination of a similar tumor, described in a previous publication as a cerebral schwannoma, with identical immunohistochemical techniques. The results obtained favored alteration of this diagnosis to that of meningioma. This experience has led the authors to recommend the use of immunohistochemistry techniques when evaluating unusual intracranial neoplasms.

Adolescent↗
PubMed1987

Long-latency reflex activity in squirrel monkeys with occlusion of the middle cerebral artery.

The primate middle cerebral artery (MCA) preparation has been studied as an animal model of human spasticity resulting from stroke. MCA occlusion in 3 squirrel monkeys was accomplished through a transorbital approach and animals were evaluated by 'clinical' examinations and studies of EMG responses to torque motor imposed joint displacement. Animals were transiently hemiparetic but not spastic postoperatively, although all were found to have a large infarct in MCA territory on post-mortem examination. The electromyographic (EMG) response of biceps in normal animals to torque motor imposed elbow extension consisted of both early (M1) and late (M2) components (Tatton et al. 1975). These components were unchanged following MCA occlusion. The EMG response to metacarpophalangeal joint extension in finger flexors or normal animals consisted solely of a long-latency (M2) component (Lenz et al. 1983a). Following MCA occlusion the M2 component in this muscle was decreased or absent, but a short-latency (M1) component appeared.

Animals↗
PubMedDate not supplied

Classification of 1H MR spectra of human brain neoplasms: the influence of preprocessing and computerized consensus diagnosis on classification accuracy.

We study how classification accuracy can be improved when both different data preprocessing methods and computerized consensus diagnosis (CCD) are applied to 1H magnetic resonance (MR) spectra of astrocytomas, meningiomas, and epileptic brain tissue. The MR spectra (360 MHz, 37 degrees C) of tissue specimens (biopsies) from subjects with meningiomas (95; 26 cases), astrocytomas (74; 26 cases), and epilepsy (37; 8 cases) were preprocessed by several methods. Each data set was partitioned into training and validation sets. Robust classification was carried out via linear discriminant analysis (LDA), artificial neural nets (NN), and CCD, and the results were compared with histopathological diagnosis of the MR specimens. Normalization of the relevant spectral regions affects classification accuracy significantly. The spectra-based average three-class classification accuracies of LDA and NN increased from 81.7% (unnormalized data sets) to 89.9% (normalized). CCD increased the classification accuracy of the normalized sets to an average of 91.8%. CCD invariably decreases the fraction of unclassifiable spectra. The same trends prevail, with improved results, for case-based classification. Preprocessing the 1H MR spectra is essential for accurate and reliable classification of astrocytomas, meningiomas, and nontumorous epileptic brain tissue. CCD improves classification accuracy, with an attendant decrease in the fraction of unclassifiable spectra or cases.

Astrocytoma↗
PubMedDate not supplied

Congenital ependymoblastoma presenting as a sacrococcygeal mass in a newborn: an immunohistochemical, light and electron microscopic study.

We describe a case of congenital ependymoblastoma presenting as a subcutaneous mass in the sacrococcygeal area of a newborn male. The tumor was composed of primitive cells disposed in compact sheets and cords and exhibiting focal ependymal differentiation. No other line of cellular differentiation was identified by either immunohistochemistry or ultrastructural study. Elevated serum alpha-fetoprotein was found, which decreased following surgical extirpation of the tumor. We propose that this tumor had its origin in the ependymal medullary vestige, similar to other sacrococcygeal ependymomas.

Antigens, Neoplasm↗
PubMedDate not supplied

"Polyphenotypic" tumors in the central nervous system: problems in nosology and classification.

In recent years, there is increasing recognition of polyphenotypic high-grade malignancies in the non-central nervous system (CNS) tumor literature. Some of these tumors have been regarded as variants of primitive neuroectodermal tumor (PNET) or as extrarenal malignant rhabdoid tumors (MRTs). This report concerns two posterior fossa neoplasms, both of which displayed a "polyphenotypic" expression of neural, epithelial, myogenic, and glial markers, including synaptophysin, neurofilament, vimentin, glial fibrillary acidic protein, S-100, neuron-specific enolase, desmin, S antigen, MIC2, cytokeratin, epithelial membrane antigen, and carcinoembryonic antigen. One tumor showed complex intercellular junctions, cytoplasmic intermediate filaments, well-developed rough and smooth endoplasmic reticulum and Golgi apparatus, cilia, and neurosecretory granules. The other neoplasm showed pools of glycogen, desmosomes, and tonofilaments. The histological and ultrastructural appearances were inconsistent with glioma, PNET, meningioma, ependymoma, choroid plexus carcinoma, sarcoma, germ cell tumor, and other tumors in the World Health Organization classification. Although the polyphenotype raises the issue that these may represent variants of MRT or the atypical teratoid-rhabdoid tumor, the morphologic findings in the two cases were very dissimilar. Our two cases underscore the problems in nosology and classification of polyphenotypic tumors of the CNS. This is particularly significant, as therapeutic protocols for PNET, MRT, and non-CNS polyphenotypic tumors are different. We review the literature on polyphenotypic tumors and reiterate the difficulties in precise classification of these complex tumors.

Biomarkers↗