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M D King

Publications and source records attributed to M D King.

At least 55 records · Page 3Linked to original sources
PubMed1996

Lateralization of brain function in childhood revealed by magnetic resonance spectroscopy.

We used proton magnetic resonance spectroscopy (1H MRS) for the assessment of focal brain pathology in 22 right-handed children with a diagnosis of intractable temporal lobe epilepsy, and we related this pathology to cognitive dysfunction. Cognitive assessment was based on measurements of verbal IQ, performance IQ, and the Paired Associate Learning subtest of the Wechsler Memory Scale. Five of the 22 children showed no abnormalities of the temporal lobes on 1H MRS, seven showed unilateral pathology, and 10 showed bilateral abnormalities. We found that left-sided pathology is associated with a loss of verbal cognitive functions, whereas right-sided pathology is associated with a loss of nonverbal functions. These findings are consistent with the pattern of lateralization of brain function that has been observed in adults.

Adolescent↗
PubMed1995

Identification of collaterally perfused areas following focal cerebral ischemia in the rat by comparison of gradient echo and diffusion-weighted MRI.

Diffusion-weighted (DW) and gradient echo (GE) magnetic resonance images were acquired before and after occlusion of the middle cerebral artery (MCA) in the rat. Upon occlusion, an increase in DW imaging signal intensity was observed in a core area within the MCA territory, most likely reflecting cytotoxic edema. The signal from GE images, which is sensitive to changes in the absolute amount of deoxyhemoglobin, decreased following ischemia within a region that extended beyond the core area observed with DW imaging. This hypointensity is attributed to increases in blood volume and/or oxygen extraction fraction, which result from a decrease in perfusion pressure in the collaterally perfused area. The evolution of the GE imaging signal intensity from different regions was studied for 3.5 h following the occlusion. In the core area, the GE imaging signal returned towards baseline values after approximately 1-2 h, while it remained stable in the surrounding area. This feature may reflect a decrease in hematocrit due to microcirculatory defect and/or a decrease in the oxygen extraction fraction due to ongoing infarction of the tissue and may indicate that tissue recovery is severely compromised. The combined use of DW and GE imaging offers great promise for the noninvasive identification of specific pathological events with high spatial resolution.

Animals↗
PubMed1995

Molecular and cellular analysis of the DNA repair defect in a patient in xeroderma pigmentosum complementation group D who has the clinical features of xeroderma pigmentosum and Cockayne syndrome.

Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are quite distinct genetic disorders that are associated with defects in excision repair of UV-induced DNA damage. A few patients have been described previously with the clinical features of both disorders. In this paper we describe an individual in this category who has unusual cellular responses to UV light. We show that his cultured fibroblasts and lymphocytes are extremely sensitive to irradiation with UV-C, despite a level of nucleotide excision repair that is 30%-40% that of normal cells. The deficiency is assigned to the XP-D complementation group, and we have identified two causative mutations in the XPD gene: a gly-->arg change at amino acid 675 in the allele inherited from the patient's mother and a -1 frameshift at amino acid 669 in the allele inherited from his father. These mutations are in the C-terminal 20% of the 760-amino-acid XPD protein, in a region where we have recently identified several mutations in patients with trichothiodystrophy.

Cells, Cultured↗
PubMed1994

Photoaffinity labelling of the active site of the rat glutathione transferases 3-3 and 1-1 and human glutathione transferase A1-1.

The glutathione transferases (GSTs) form a group of enzymes responsible for a wide range of molecular detoxications. The photoaffinity label S-(2-nitro-4-azidophenyl)glutathione was used to study the hydrophobic region of the active site of the rat liver GST 1-1 and 2-2 isoenzymes (class Alpha) as well as the rat class-Mu GST 3-3. Photoaffinity labelling was carried out using a version of S-(2-nitro-4-azidophenyl)glutathione tritiated in the arylazido ring. The labelling occurred with higher levels of radioisotope incorporation for the Mu than the Alpha families. Taking rat GST 3-3, 1.18 (+/- 0.05) mol of radiolabel from S-(2-nitro-4-azidophenyl)glutathione was incorporated per mol of dimeric enzyme, which could be blocked by the presence of the strong competitive inhibitor, S-tritylglutathione (Ki = 1.4 x 10(-7) M). Radiolabelling of the protein paralleled the loss of enzyme activity. Photoaffinity labelling by tritiated S-(2-nitro-4-azidophenyl)glutathione on a preparative scale (in the presence and absence of S-tritylglutathione) followed by tryptic digestion and purification of the labelled peptides indicated that GST 3-3 was specifically photolabelled; the labelled peptides were sequenced. Similarly, preparative photoaffinity labelling by S-(2-nitro-4-azidophenyl)glutathione of the rat liver 1-1 isoenzyme, the human GST A1-1 and the human-rat chimaeric GST, H1R1/1, was carried out with subsequent sequencing of radiolabelled h.p.l.c.-purified tryptic peptides. The results were interpreted by means of molecular-graphics analysis to locate photoaffinity-labelled peptides using the X-ray-crystallographic co-ordinates of rat GST 3-3 and human GST A1-1. The molecular-graphical analysis indicated that the labelled peptides are located within the immediate vicinity of the region occupied by S-substituted glutathione derivatives bound in the active-site cavity of the GSTs investigated.

Affinity Labels↗
PubMed1994

q-Space imaging of the brain.

q-Space imaging (Callaghan, J. Magn. Reson. 88, 493 (1990)) has been used to obtain mouse brain water displacement profiles. These profiles take the form of a unidirectional incoherent-displacement probability density distribution. Two groups of mice were studied, a normal group and one in which surgery had been performed to reduce the supply of blood to the forebrain. In the normal group the incoherent displacement of water was reduced postmortem. Four of the surgically treated mice yielded displacement profiles that resembled those obtained postmortem; the remaining two were near normal. This study demonstrates the feasibility of in vivo q-space imaging. The displacement profile changes that occur subsequent to an interruption of the forebrain blood supply are consistent with the hyperintensity changes seen in diffusion-weighted imaging.

Animals↗
PubMed1994

Monitoring the initial expansion of focal ischaemic changes by diffusion-weighted MRI using a remote controlled method of occlusion.

The purpose of the present study was to quantify the early changes which occur on diffusion-weighted imaging following focal cerebral ischaemia. We have developed a method for the remote occlusion of the middle cerebral artery in the rat, allowing early changes to be monitored and images to be acquired before and after ischaemia under identical conditions. Sequential diffusion-weighted images were acquired before and for up to 6 h following the occlusion. The data show that a hyperintense area appears soon after occlusion which expands during the first 2 h. It has previously been shown that the hyperintensity observed after ischaemia is linked to events associated with energy failure. Our findings are in good agreement with previous pathophysiological studies of focal ischaemia, which suggest a growing of the energy depleted area. In conclusion, our data extend the usefulness of diffusion-weighted imaging to the study of the early spatial evolution of the most compromised area after focal ischaemia. Diffusion-weighted imaging may constitute a very powerful tool to investigate pharmacological therapies which may interact with this evolution, both in experimental and clinical studies.

Animals↗
PubMed1994

Magnetic resonance spectroscopy in temporal lobe epilepsy.

We used proton magnetic resonance spectroscopy (1H MRS) to investigate the temporal lobes of 25 patients with temporal lobe epilepsy. Spectra were obtained from 2 x 2 x 2 cm cubes in the medial region of the temporal lobe, and were analyzed on the basis of signals from N-acetylaspartate (NAA), creatine + phosphocreatine (Cr), and choline-containing compounds (Cho). In comparison with control subjects, the temporal lobes ipsilateral to the seizure focus showed a mean reduction of 22% in the NAA signal, with a 15% increase in the Cr signal and a 25% increase in the Cho signal. There were smaller effects in the contralateral temporal lobes. These spectral abnormalities may reflect neuronal loss or damage, together with reactive astrocytosis. The NAA/Cho+Cr ratio was abnormally low in 88% of the patients, 40% showing bilateral effects. On the basis of the NAA/Cho+Cr ratio, we correctly achieved lateralization in 15 cases, with three incorrect. Two of the incorrect lateralizations also had imaging abnormalities on the contralateral side, and the other had severe bilateral abnormalities on MRS. We conclude that 1H MRS provides useful information in the preoperative investigation of patients with temporal lobe epilepsy, contributing to lateralization and detecting bilateral abnormalities.

Adolescent↗
PubMed1993

Applications of NMR spectroscopy to the study of experimental stroke in vivo.

BACKGROUND AND PURPOSE: Magnetic resonance spectroscopy and imaging enable us to investigate biochemical and pathophysiological changes associated with cerebral ischemia. The specific aims of these studies were to establish the relationships between energy metabolites and regional cerebral blood flow and to determine whether diffusion-weighted imaging is sensitive to the known thresholds for cerebral tissue energy failure and disturbance of transmembrane ionic gradients in gerbils. METHODS: Magnetic resonance spectroscopy measurements of energy metabolites in the gerbil brain were obtained as a function of cerebral blood flow (measured with the hydrogen clearance technique) before, during, and after unilateral or bilateral occlusion of the common carotid arteries. Diffusion-weighted and T2-weighted images were obtained in a separate series of experiments. RESULTS: Major changes in brain energy metabolites were observed at flow values of 20 ml.100 g-1.min-1 and below. The cerebral blood flow threshold for maintenance of energy status was lowered in hypothermia, consistent with a protective effect. Diffusion-weighted imaging intensity increased at cerebral blood flow values of 15 to 20 ml.100 g-1.min-1 and below and increased gradually following the onset of severe global cerebral ischemia, but with a delay of about 2.5 minutes. CONCLUSIONS: The spectroscopic observations suggest that the flow thresholds for electrical function and edema are a direct consequence of energy failure. Comparison of the spectroscopy and imaging data suggests that diffusion-weighted imaging is sensitive to disruption of tissue energy metabolism or to a consequence of this disruption. The possibilities arise of visualizing energy failure with the spatial resolution characteristic of magnetic resonance imaging and detecting compromised but recoverable tissue.

Animals↗
PubMed1992

Perfusion and diffusion MR imaging.

Diffusion-weighted images of the rat brain were obtained using the pulsed-gradient spin-echo method. An attempt was made to extract perfusion-related parameters from signal intensity data taken from the caudate-putamen region of the images, by using a nonlinear least-squares calculation to fit the Le Bihan biexponential expression (Le Bihan et al., Radiology, 168, 497 (1988)) to the data. The perfusion-related parameters could not be obtained with sufficient accuracy to be useful, although the perfusion-weighted images appear to contain meaningful qualitative information. An analysis of the perfusion model is presented and shows why the Le Bihan pseudo-diffusion coefficient is particularly difficult to measure with reasonable accuracy.

Animals↗
PubMed1992

Diffusion-weighted imaging studies of cerebral ischemia in gerbils. Potential relevance to energy failure.

BACKGROUND AND PURPOSE: Diffusion-weighted magnetic resonance imaging has been shown to be particularly suited to the study of the acute phase of cerebral ischemia in animal models. The studies reported in this paper were undertaken to determine whether this technique is sensitive to the known ischemic thresholds for cerebral tissue energy failure and disturbance of membrane ion gradients. METHODS: Diffusion-weighted images of the gerbil brain were acquired under two sets of experimental conditions: as a function of cerebral blood flow after controlled graded occlusion of the common carotid arteries (partial ischemia), as a function of time following complete bilateral carotid artery occlusion (severe global ischemia), and on deocclusion after 60 minutes of ischemia. RESULTS: During partial cerebral ischemia, the diffusion-weighted images remained unchanged until the cerebral blood flow was reduced to 15-20 ml.100 g-1.min-1 and below, when image intensity increased as the cerebral blood flow was lowered further. This is similar to the critical flow threshold for maintenance of tissue high-energy metabolites and ion homeostasis. After the onset of severe global cerebral ischemia, diffusion-weighted image intensity increased gradually after a delay of approximately 2.5 minutes, consistent with complete loss of tissue adenosine triphosphate and with the time course of increase in extracellular potassium. This hyperintensity decreased on deocclusion following 60 minutes of ischemia. CONCLUSIONS: The data suggest that diffusion-weighted imaging is sensitive to the disruption of tissue energy metabolism or a consequence of this disruption. This raises the possibility of imaging energy failure noninvasively. In humans, this could have potential in visualizing brain regions where energy metabolism is impaired, particularly during the acute phase following stroke.

Animals↗
PubMed1992

T2- and diffusion-weighted magnetic resonance imaging of a focal ischemic lesion in rat brain.

BACKGROUND AND PURPOSE: We sought to evaluate the application of T2-weighted and diffusion-weighted magnetic resonance imaging techniques in the study of a focal ischemic lesion in the rat brain. METHODS: Unilateral cortical infarcts were induced using the photosensitive dye rose bengal and 560 nm light irradiation. Magnetic resonance images were recorded from a total of 11 rats at selected intervals from 1.5 hours to several days after induction of the lesion. Parallel experiments were performed in which Evans blue dye was injected into the lesioned animals either immediately after lesion induction (n = 11) or 1 hour before the animals were killed (n = 11). The second procedure was designed to show regions of blood-brain barrier permeability to plasma proteins at the time of sacrifice, whereas the first procedure showed the accumulation and subsequent dispersion of plasma protein following disruption of the blood-brain barrier. RESULTS: Regions of the cortex highlighted by the T2-weighted images corresponded well to the pattern of dye staining seen from the first procedure while the diffusion-weighted images showed visual correspondence with the staining pattern obtained using the second procedure. CONCLUSIONS: These results illustrate the complementary use of T2-weighted and diffusion-weighted magnetic resonance imaging in discerning the pathophysiology of developing lesions.

Animals↗
PubMed1991

Diffusion-weighted imaging of kainic acid lesions in the rat brain.

We present T2-weighted and diffusion-weighted images of kainic acid lesions in the rat brain. Our observations show improved image contrast between edematous lesions and unaffected tissue using diffusion-weighted imaging. Furthermore, we show that the anisotropic intensity changes associated with this sequence can be used to highlight white matter tracts and to provide information concerning their orientation in the rat brain.

Amygdala↗
PubMed1989

Polymorphic phase behavior of lysopalmitoylphosphatidylcholine in poly(ethylene glycol)-water mixtures.

The polymorphic phase behavior of 1-palmitoyl-2-lyso-sn-glycero-3-phosphocholine dispersions in excess water has been studied as a function of temperature and poly(ethylene glycol) (PEG) concentration, using proton dipolar-decoupled 31P NMR spectroscopy and turbidity measurements. The phase behavior was found to depend on both lipid concentration and PEG concentration, and most of the NMR experiments were conducted at a lipid concentration of 15 mg/mL. At low PEG concentrations (0-12 wt %), a thermotropic transition occurs at 3-5 degrees C with increasing temperature, from an interdigitated lamellar gel (L beta i) phase to a normal micellar phase. At intermediate PEG concentrations (12-20 wt %), thermotropic transitions take place with increasing temperature, first from the lamellar gel phase to a fluid cubic (Q alpha) phase and then at higher temperatures from the cubic phase to the micellar phase. At intermediate PEG concentrations above the former range (20-30 wt %), thermotropic transitions take place with increasing temperature, first from the lamellar gel phase to the cubic phase, then from the cubic phase to a normal hexagonal (HI) phase, and finally from the hexagonal phase to the micellar phase. At high PEG concentrations (greater than 30 wt %), a thermotropic transition takes place with increasing temperature from the lamellar gel phase directly to the fluid hexagonal phase. At these high PEG concentrations, the micellar phase is not attained within the accessible temperature range (less than or equal to 90 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)

Kinetics↗
PubMed1988

Cytochrome oxidase deficiency: immunological studies of skeletal muscle mitochondrial fractions.

We report a 2-year-old girl who presented with delayed development, weakness and persistent vomiting. She had a demyelinating peripheral neuropathy. The activity of cytochrome oxidase in skeletal muscle from the patient was 10% of controls. Immunochemical studies using antibodies to holo-cytochrome oxidase and the individual subunits showed a low concentration of all detectable subunits.

Child, Preschool↗