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Biomedical subjects

M D King

Publications and source records attributed to M D King.

At least 37 records · Page 2Linked to original sources
PubMed2000

Familial Prader-Willi syndrome: case report and a literature review.

Prader-Willi syndrome (PWS) is a neurobehavioural disorder arising through a number of different genetic mechanisms. All involve loss of paternal gene expression from chromosome 15q11q13. Although the majority of cases of PWS are sporadic, precise elucidation of the causative genetic mechanism is essential for accurate genetic counselling as the recurrence risk varies according to the mechanism involved. A pair of siblings affected by PWS is described. Neither demonstrates a microscopically visible deletion in 15q11q13 or maternal disomy. Methylation studies at D15S63 and at the SNRPN locus confirm the diagnosis of PWS. Molecular studies reveal biparental inheritance in both siblings with the exception of D15S128 and D15S63 where no paternal contribution is present indicating a deletion of the imprinting centre. Family studies indicate that the father of the siblings carries the deletion which, he has inherited from his mother. The recurrence risk for PWS in his offspring is 50%.

Alleles↗
PubMed2000

Hashimoto's thyroiditis--a rare but treatable cause of encephalopathy in children.

Hashimoto's encephalopathy is a very rare complication of Hashimoto's thyroiditis. It is a progressive or relapsing encephalopathy associated with elevation of thyroid specific autoantibodies. Patients usually present when euthyroid and this diagnosis should be considered in any unexplained encephalopathy or progressive cognitive decline in the euthyroid patient.

Adolescent↗
PubMed2000

Deficiency of dolichol-phosphate-mannose synthase-1 causes congenital disorder of glycosylation type Ie.

Congenital disorders of glycosylation (CDG), formerly known as carbohydrate-deficient glycoprotein syndromes, lead to diseases with variable clinical pictures. We report the delineation of a novel type of CDG identified in 2 children presenting with severe developmental delay, seizures, and dysmorphic features. We detected hypoglycosylation on serum transferrin and cerebrospinal fluid beta-trace protein. Lipid-linked oligosaccharides in the endoplasmic reticulum of patient fibroblasts showed an accumulation of the dolichyl pyrophosphate Man(5)GlcNAc(2) structure, compatible with the reduced dolichol-phosphate-mannose synthase (DolP-Man synthase) activity detected in these patients. Accordingly, 2 mutant alleles of the DolP-Man synthase DPM1 gene, 1 with a 274C>G transversion, the other with a 628delC deletion, were detected in both siblings. Complementation analysis using DPM1-null murine Thy1-deficient cells confirmed the detrimental effect of both mutations on the enzymatic activity. Furthermore, mannose supplementation failed to improve the glycosylation status of DPM1-deficient fibroblast cells, thus precluding a possible therapeutic application of mannose in the patients. Because DPM1 deficiency, like other subtypes of CDG-I, impairs the assembly of N-glycans, this novel glycosylation defect was named CDG-Ie.

Amino Acid Sequence↗
PubMed1999

Early changes in water diffusion, perfusion, T1, and T2 during focal cerebral ischemia in the rat studied at 8.5 T.

The time evolution of water diffusion, perfusion, T1, and T2 is investigated at high magnetic field (8.5 T) following permanent middle cerebral artery occlusion in the rat. Cerebral blood flow maps were obtained using arterial spin tagging. Although the quantitative perfusion measurements in ischemic tissue still pose difficulties, the combined perfusion and diffusion data nevertheless distinguish between a "moderately affected area," with reduced perfusion but normal diffusion; and a "severely affected area," in which both perfusion and diffusion are significantly reduced. Two novel magnetic resonance imaging observations are reported, namely, a decrease in T2 and an increase in T1, both within the first few minutes of ischemia. The rapid initial decrease in T2 is believed to be associated with an increase in deoxyhemoglobin levels, while the initial increase in T1 may be related to several factors, such as flow effects, an alteration in tissue oxygenation, and changes in water environment.

Animals↗
PubMed1999

Reperfusion in a gerbil model of forebrain ischemia using serial magnetic resonance FAIR perfusion imaging.

BACKGROUND AND PURPOSE: Existing methods for the quantitative measurement of the changing cerebral blood flow (CBF) during reperfusion suffer from poor spatial or temporal resolution. The aim of this study was to implement a recently developed MRI technique for quantitative perfusion imaging in a gerbil model of reperfusion. Flow-sensitive alternating inversion recovery (FAIR) is a noninvasive procedure that uses blood water as an endogenous tracer. METHODS: Bilateral forebrain ischemia of 4 minutes' duration was induced in gerbils (n=8). A modified version of FAIR with improved time efficiency was used to provide CBF maps with a time resolution of 2.8 minutes after recirculation had been initiated. Quantitative diffusion imaging was also performed at intervals during the reperfusion period. RESULTS: On initiating recirculation after the transient period of ischemia, the FAIR measurements demonstrated either a symmetrical, bilateral pattern of flow impairment (n=4) or an immediate side-to-side difference that became apparent with respect to the cerebral hemispheres in the imaged slice (n=4). The flow in each hemisphere displayed a pattern of recovery close to the preocclusion level or, alternatively, returned to a lower level before displaying a delayed hypoperfusion and a subsequent slow recovery. The diffusion measurements during this latter response suggested the development of cell swelling during the reperfusion phase in the striatum. CONCLUSIONS: The CBF during the reperfusion period was monitored with a high time resolution, noninvasive method. This study demonstrates the utility of MRI techniques in following blood flow changes and their pathophysiological consequences.

Animals↗
PubMed1999

Metabolism and morphology of brown adipose tissue from Brahman and Angus newborn calves.

The objective of this study was to compare adipocyte morphology and lipogenesis between breed types (Angus vs Brahman) in brown adipose tissue (BAT) and white adipose tissue (WAT) from newborn calves. The Brahman calves (n = 7) were born during the fall season, whereas the Angus calves were born in fall (n = 6) or the following spring (n = 4). At parturition, Brahman cows were lighter than fall Angus cows, but were heavier than spring Angus cows (P < .05). Birth weights and perirenal BAT weights were greater in spring-born, but not in fall-born Angus calves, than in Brahman calves (P < .05). Fall-born Angus BAT contained 63% more (P < .05) adipocytes/100 mg tissue and contained a greater proportion (P < .05) of adipocytes with mean diameters of 40 to 50 microm, and fewer adipocytes with diameters of 60 microm or greater, than Brahman BAT. Brahman BAT contained two-to-three times as many beta-receptors as Angus BAT (P < .05), although the dissociation constant (Kd) was not different between breed types. Mitochondria in Brahman BAT were primarily spherical, whereas Angus BAT mitochondria were elongated, and mitochondrial cross-sectional area tended (P = .08) to be greater in Brahman BAT than in Angus BAT. The mitochondrial uncoupling protein (UCP) mRNA concentration (per 10(6) cells) was greater in Brahman BAT than in BAT from fall-born Angus calves. Lipogenesis from acetate was greater in Angus BAT than in Brahman BAT (P < .05), and glucose and palmitate contributed a greater proportion of carbon to lipogenesis in Brahman BAT than in Angus BAT. These differences in lipogenesis between breed types were not observed in s.c. WAT. The WAT from both breed types contained adipocytes with distinct brown adipocyte morphology, suggesting an involution of BAT to WAT in utero. We conclude that differences in UCP gene expression cannot cause the greater peak thermogenesis of Angus calves; however, differences between breed types in lipid metabolism and(or) mitochondrial morphology may contribute to this phenomenon.

Adipose Tissue↗
PubMed1998

Merosin-deficient congenital muscular dystrophy and cortical dysplasia.

Congenital muscular dystrophy (CMD) encompasses a heterogenous group of muscle disorders with autosomal recessive inheritance, characterized by muscular weakness and hypotonia at birth or within the first few months of life and developmental delay. Merosin-deficient CMD is a clinically distinct form which may be associated with significant abnormalities of the brain detectable by neuroimaging. We report two siblings of consanguineous parents with merosin-deficient CMD in an Irish family who in addition to the characteristic white matter abnormalities on neuroimaging, had occipital dysplasia. Clinical, electrophysiological muscle biopsy findings and neuroimaging were very similar in both cases. Although merosin-deficient CMD with white matter abnormalities on neuroimaging is well documented in the literature, the association with occipital dysplasia has only rarely been reported. The appearance of an identical cortical defect in these siblings suggests an underlying genetic mechanism.

Biopsy↗
PubMed1998

Chronic active destructive herpes simplex encephalitis with recovery of viral DNA 12 years after disease onset.

Acute herpes simplex encephalitis (HSE) carries significant morbidity and mortality even after early treatment with antiviral agents (7). As well as causing acute neurological disease, Herpes viruses are associated with relapsing--remitting (Varicella--Zoster, Epstein-Barr) and chronic (Rasmussen encephalitis) disease processes (1). A two-year-old girl developed acute HSE which was followed by a 10-year neurologic illness characterised by asymmetric spastic tetraparesis, pseudobulbar palsy, the opercular syndrome of Foix-Chavany-Marie (4) and seizures. The neurological signs remained static until the child died suddenly 12 years after disease onset. Neuropathologic examination demonstrated active chronic encephalitis. Herpes simplex virus (HSV) DNA was recovered from formalin-fixed paraffin-embedded brain tissue. This case provides additional evidence for the development of chronic neurological disease attributable to persistence of herpes simplex virus type 1.

Brain↗
PubMed1998

Aicardi-Goutières syndrome: an expanding phenotype.

The Aicardi-Goutières syndrome (AGS) is an autosomal recessive progressive encephalopathy associated with basal ganglia calcification, white-matter abnormality, cerebro-spinal fluid (CSF) pleocytosis and elevated CSF interferon alpha (IFN alpha). Two brothers of consanguineous parents who presented in the first year with developmental delay are reported. The first boy is normocephalic with spastic diplegia and normal I.Q. Tests in the second year of life showed punctate calcification of the basal ganglia and subcortical white matter and CSF pleocytosis. At 9 years clinical and imaging features are unchanged and CSF including IFN alpha is normal. The second boy at 21 months has dystonic cerebral palsy, slight fall-off in head growth and cognitive delay. Imaging abnormalities are more severe than those in the brother, CSF examination reveals pleocytosis and marked increase in IFN alpha. Detailed metabolic and viral studies were negative in both cases. Although the clinical course is not progressive, it is suggested that the brothers have AGS and represent the mild end of the spectrum of the disorder. CSF examination (including IFN alpha), should be performed early in children with an apparently static encephalopathy and brain calcification, as typical abnormalities decrease or disappear with age.

Basal Ganglia Diseases↗
PubMed1998

Familial cerebellar hypoplasia and pancytopenia without chromosomal breakages.

Two siblings manifested a neuro-haematologic syndrome characterised by low birth weight, failure to thrive, chronic persistent tongue ulceration, severe truncal ataxia and pancytopenia without either telangiectasia or chromosomal instability. One sibling died from sepsis and the cerebellum demonstrated reduced cellularity of the molecular and granular layers with relative preservation of Purkinje cells and minimal gliosis. A surviving sibling has shown haematologic progression to a myelodysplastic disorder. There was no evidence of any chromosomal instability following exposure of fibroblasts and lymphocytes to irradiation. Monosomy-7 was not present in the surviving sibling. We suspect that these two patients represent another example of the rare Hoyeraal-Hreidarsson syndrome and we are currently engaged in very close monitoring of the surviving sibling for evidence of any karyotypic abnormality.

Ataxia↗
PubMed1997

The spectrum of hippocampal sclerosis: a quantitative magnetic resonance imaging study.

One hundred patients with intractable temporal lobe epilepsy and 22 control subjects were scanned on a 1.5-T Siemens SP63 Magnetom scanner. A combination of hippocampal T2 mapping, hippocampal volume measurement corrected for intracranial volume, and inspection of hippocampal morphology on a hippocampal volume distribution graph compared with a control graph revealed previously undetected forms of bilateral hippocampal sclerosis and four false-positive diagnoses of hippocampal sclerosis made on visual inspection of the scans. A physiological asymmetry in the position of the hippocampi in 41% of control subjects and focal hippocampal atrophies in patients made measurement of the whole length of the hippocampus mandatory. The extent of hippocampal damage in patients with hippocampal sclerosis correlated with the number of secondary generalized seizures during a patient's lifetime. In contrast to patients with unilateral hippocampal sclerosis, patients with severe bilateral hippocampal sclerosis had no history of febrile convulsions. Twenty-six patients with intractable temporal lobe epilepsy had normal hippocampal magnetic resonance imaging measures and as a group were significantly older at the onset of habitual epilepsy than were patients with hippocampal sclerosis. In conclusion, a combination of quantitative magnetic resonance imaging techniques revealed a spectrum of hippocampal sclerosis and optimally defined boundaries of hippocampal normality. The spectrum of hippocampal sclerosis is related to the etiology, the number of secondary generalized seizures, and the age at onset of habitual epilepsy.

Adolescent↗
PubMed1997

Quantitative neuropathology and quantitative magnetic resonance imaging of the hippocampus in temporal lobe epilepsy.

The aims of this study were to examine the relationships of hippocampal T2 (HCT2) relaxation time and magnetic resonance (MR)-based hippocampal volume (HCV) to neuronal (ND) and glial cell densities (GD) of hippocampal neuronal cell layers, and to obtain a better clinicopathological definition of hippocampal sclerosis (HS) and end folium sclerosis (EFS). Fifty-three hippocampi with HS, 6 with EFS, and 6 control hippocampi were studied. Pathologically, the HS group had a significantly higher logarithm (log) GD/ND than the controls in all hippocampal subregions, and than the EFS group in all subregions except the granule cell layer of the dentate gyrus (GCDG). The EFS group had a significantly higher log GD/ND than the control group only in the GCDG. Clinical correlations suggested that EFS may be the consequence of temporal lobe seizures and not an epileptogenic entity. Hippocampal atrophy in HS was associated with neuronal cell depletion and concomitant gliosis in the cornu Ammonis (CA) 1, CA2, CA3, and hilus. An increased HCT2 was associated with damage in the CA1 and also the hilus and has a different neuropathological basis than HCV loss. MR-based HCV measurement and HCT2 mapping, therefore, give complementary information in the presurgical evaluation of temporal lobe epilepsy and longitudinal studies.

Adolescent↗
PubMed1997

Effects of diffusion anisotropy on lesion delineation in a rat model of cerebral ischemia.

The effects of white and gray matter diffusion anisotropy on ischemic lesion delineation have been studied in the rat model of middle cerebral artery occlusion. Apparent diffusion coefficient (ADC) maps obtained by conventional pulsed gradient spin echo diffusion-weighted imaging (PGSE-DWI) were compared with maps of the trace of the diffusion tensor in both normal and occluded animals. Diffusion tensor trace maps were derived from the average of the ADC maps from three separate experiments with diffusion weighting along three orthogonal axes, and also from a single-scan method. A marked degree of diffusion anisotropy was observed in both cortical gray matter and white matter from ADC maps of the control animals. In the occluded animals, the systematic effects of anisotropy on ADC and lesion area influenced the delineation of the ischemic territory in the PGSE-DWI ADC maps. However, the two trace methods eliminated these effects and gave consistent ischemic lesion depiction, despite the use of differing diffusion times in the two measurements.

Animals↗
PubMed1997

Localized q-space imaging of the mouse brain.

Localized q-space imaging was used to obtain water displacement profiles from mouse brain. These profiles take the form of unidirectional diffusive displacement probability distributions. Two groups of mice were studied, a normal group and a group in which surgery had been performed to produce a unilateral reduction in the supply of blood to the forebrain. q-Space measurements were made both in vivo and postmortem. The displacement profiles were characterized using the summary parameter prob[d < 10], which is the proportion of water molecules that undergo a net diffusive displacement that is less than +/-10 microm, during the diffusion period (50 ms). The range of prob[d < 10] values in the normal group was 0.71 to 0.77 in vivo compared with 0.78 to 0.87 in the impaired hemisphere of the surgically treated group. An increase in prob[d < 10] occurred postmortem to yield values in the range 0.79 to 0.81 and 0.80 to 0.89 in the normal and surgically treated group, respectively. These observations are consistent with the diffusion-weighted image intensity changes that occur after a period of ischemia.

Animals↗
PubMed1997

Acute near-fatal parainfectious cerebellar swelling with favourable outcome.

The clinical course, neuro-imaging features and neuropathologic findings in a child with para-infectious acute cerebellar swelling are described. Reversible transtentorial and transforaminal herniations occurred and required emergency posterior fossa decompression with external ventricular drainage. Neuropathologic examination of a cerebellar biopsy demonstrated a subacute pathogen-free cerebellitis. Following neurosurgical intervention and steroid therapy, symptoms and signs resolved and the patient is well 3 years later. Acute para-infectious cerebellar swelling is potentially fatal unless recognised and treated early in its evolution.

Cerebellar Diseases↗