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Biomedical subjects

M D King

Publications and source records attributed to M D King.

At least 19 recordsLinked to original sources
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↗
PubMed1987

Head group and chain length dependence of phospholipid self-assembly studied by spin-label electron spin resonance.

The critical micelle concentrations (cmc's) of a variety of spin-labeled phospholipids, 1-acyl-2-[4-(4,4-dimethyloxazolidine-N-oxyl)valeryl]-sn-glycero-3-pho sph o derivatives, have been determined by electron spin resonance (ESR) spectroscopy. The narrow, three-line ESR spectra of the rapidly tumbling monomers are clearly distinguished from the spin-spin broadened spectra of the micellar aggregates, allowing a direct determination of the concentrations of the two species. The influence of both the hydrocarbon chain length and the polar head group on the energetics of self-assembly has been studied. For phosphatidylcholine, 1n [cmc] decreases linearly with the length of the sn-1 chain. The gradient of this linear dependence corresponds to a free energy of transfer of the monomer from the aqueous phase to the micelle of delta Gtr = -1.1RT per CH2 group. The cmc's of the 1-lauroyl derivatives of both phosphatidylcholine and phosphatidylglycerol have relatively shallow, biphasic temperature dependences with a minimum at approximately 20 degrees C. Both of these properties are characteristic of the hydrophobic effect, with the free energy of transfer being slightly less than that for the solubility of n-hydrocarbons in water, corresponding to the reduced configurational entropy of the lipid chains in the micellar state. The cmc's of the 1-lauroyl derivatives of the phospholipids in 0.15 M NaCl, for their various charge states, are as follows: phosphatidic acid(2-), 0.77 mM; phosphatidic acid(1-), 0.13 mM; phosphatidylserine(1-), 0.24 mM; phosphatidylglycerol(1-), 0.17 mM; phosphatidylcholine, 0.10 mM; phosphatidylethanolamine, 0.05 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Electron Spin Resonance Spectroscopy↗
PubMed1987

The influence of calcium pump coupling on the Arrhenius behavior of sarcoplasmic reticulum Ca2+-ATPase.

Experiments were performed in which two batches of sarcoplasmic reticulum were isolated from rabbit hind leg muscle, one in the presence of dithiothreitol, the other in the absence of reducing agent. A comparative study was made of some of the properties of the two preparations, in particular, the Arrhenius behavior of the Ca2+-ATPase. The Ca2+-ATPase isolated in the absence of dithiothreitol is thermally unstable with the result that a triphasic Arrhenius plot was obtained. This triphasic behavior is largely the consequence of an uncoupling of the hydrolytic machinery from the calcium pump. In contrast, the sarcoplasmic reticulum preparation obtained in the presence of dithiothreitol is thermally stable and yields a linear Arrhenius plot. The difference in the Arrhenius behavior shown by the two preparations was abolished when the measurements of Ca2+-ATPase activity were made in the presence of the calcium ionophore, A23187.

Animals↗
PubMed1986

Prediction of the critical micelle concentrations of mono- and di-acyl phospholipids.

The experimental linear chainlength dependence of the logarithm of the critical micelle concentration (ln [CMC]) of mono- and di-acyl phosphatidylcholines, together with recent measurements of the polar headgroup dependence of the CMCs of a variety of spin-labelled phospholipids, and the relative solubilities of saturated and unsaturated hydrocarbons, have been combined to devise a scheme for making general predictions of the CMCs of both mono- and di-acyl phospholipids, such as are found in biological membranes.

Liposomes↗
PubMed1986

Free volume model for lipid lateral diffusion coefficients. Assessment of the temperature dependence in phosphatidylcholine and phosphatidylethanolamine bilayers.

The lipid lateral diffusion coefficients, DT, in fluid-phase phosphatidylcholine and phosphatidylethanolamine bilayers have been analysed in terms of the free-volume diffusion model by fitting the expression: DT = AT exp[- B/(T - T0)] to the observed temperature dependence, where A, B and T0 are the parameters to be optimized. Application of an unconstrained optimization procedure to data obtained from excimer formation (Galla et al. (1979) J. Membrane Biol. 48, 215-236) and from fluorescence photobleaching (Vaz et al. (1985) Biochemistry 24, 781-786) provides statistical evidence for a free-volume model as opposed to a simple Stokes-Einstein model (T0 = 0), only in certain cases. In the instances for which the parameter T0 can be determined with a reasonable degree of accuracy, it is found that this characteristic temperature at which the free volume extrapolates to zero lies below the bilayer gel-to-fluid phase transition temperature and does not coincide with the pre-transition temperature for phosphatidylcholines.

Diffusion↗
PubMed1985

Carcinoid syndrome: an unusual cause of diarrhoea.

A 9 year old girl underwent laparotomy because of intermittent diarrhoea, present since infancy. Histology of a mass at the head of pancreas and multiple hepatic nodules suggested an apudoma. Plasma serotonin and urinary excretion of 5 hydroxy indole acetic acid were raised. The child is asymptomatic four years after diagnosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Joubert's syndrome with retinal dysplasia: neonatal tachypnoea as the clue to a genetic brain-eye malformation.

Five children with features of Joubert's syndrome and Leber's amaurosis are described. The presenting symptoms were panting tachypnoea in the newborn, prolonged apnoeic attacks in the neonatal period (in both of identical twins), global developmental delay, and failure to develop vision. Three children had multiple hemifacial spasms, such as have been seen in Joubert's syndrome, and the same three had cystic dysplasia of the kidneys. Necropsy confirmed the retinal and renal pathology, together with agenesis of the vermis and brainstem dysgenesis in the identical twins. It is concluded that a gene for Leber's amaurosis may commonly manifest itself as the specific hind brain malformation underlying Joubert's syndrome. In infants with respiratory irregularities (especially rapid panting), hemifacial spasms, or developmental delay, absence of the cerebellar vermis should be specifically sought by ultrasound and computed tomography, and the electroretinogram measured, whether or not impaired vision is clinically evident.

Blindness↗