Search PubMed⌕ Search

Biomedical subjects

M D King

Publications and source records attributed to M D King.

At least 73 records · Page 4Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

Neurological sequelae of toluene abuse.

1 Twenty patients, aged eight to 14 years, were admitted to hospital over a six year period with an acute encephalopathy following toluene abuse. 2 In all cases toxicity was confined to the central nervous system. Electroencephalography performed in ten patients was abnormal in three. 3 Fourteen patients made a complete recovery, five had evidence of personality impairment but were lost to follow-up, one had a persistent cerebellar ataxia one year after admission, despite absence of exposure to toluene. 4 Solvent abuse may be impossible to establish on history, as in six of these patients. Blood assay of toluene is vital in such cases, as is an awareness that toluene abuse may lead to acute encephalopathy.

Adolescent↗

Solvent encephalopathy.

Nineteen children aged 8-14 years were admitted over a six-year period with an acute encephalopathy due to toluene intoxication. Seven had a history of euphoria and hallucinations. The remainder presented with coma (4), ataxia (3), convulsions (3), and behaviour disturbance with diplopia (2), A history of glue sniffing was elicited in 14, but in the remainder toluene assay confirmed the diagnosis. Thirteen children recovered completely; five still had psychological impairment and personality change on discharge from hospital but were lost to follow-up, and one has a persistent cerebellar ataxia one year after the acute episode, despite absence of further exposure. Toluene inhalation is an important cause of encephalopathy in children and may lead to permanent neurological damage. Diagnosis is most important if further damage due to continued abuse is to be prevented, and toluene assay is a valuable aid to diagnosis.

Adhesives↗

The modulation of Ca2+-ATPase activity of sarcoplasmic reticulum by membrane cholesterol. The effect of enzyme coupling.

The Ca2+-ATPase activity of sarcoplasmic reticulum is relatively low (less than 2 I.U.) in vesicles where enzyme activity is geared to calcium accumulation. Modulation of membrane fluidity by enriching the membrane with cholesterol has no significant effect on enzyme activity. Collapsing the Ca2+ gradient with the calcium ionophore, A23187, unmasks the inhibitory effect of membrane cholesterol on enzyme activity.

Animals↗

Controllable graded cerebral ischaemia in the gerbil: studies of cerebral blood flow and energy metabolism by hydrogen clearance and 31P NMR spectroscopy.

A technique for remotely controlling the degree of carotid artery occlusion in the gerbil model of cerebral ischaemia has been developed. The technique relies on manually adjustable nylon snares around the carotid arteries, in conjunction with a computer-based monitoring system, to control the degree of occlusion. This has allowed us to determine the dependence of energy metabolism (as assessed by 31P NMR spectroscopy) on blood flow in greater detail than was possible in our previous studies. Data obtained show that energy changes first appear at flows of 25-30 mL/100 g/min, while at flows below 20 mL/100 g/min there is a major derangement of energy metabolism. The model was used to determine the sensitivity of cerebral energy metabolism to reduced cerebral blood flow under normothermic conditions and in mild hypothermia (30 degrees C). Hypothermia had a protective effect in that energy metabolites were maintained at flows significantly below the normothermic threshold.

Adenosine Triphosphate↗

High attenuation gyri CT in postasphyxial encephalopathy.

Two term infants suffering severe asphyxial events were found to have diffusely high attenuation of the cortical gyri on CT scanning within 12 days. The findings are consistent with haemorrhagic necrosis or microcalcification. This feature has rarely been described in the literature. The evolution of the CT appearance, the possible neuropathological findings and the relationship with hypoxic-ischaemic encephalopathy are discussed.

Asphyxia Neonatorum↗

Normal and abnormal white matter tracts shown by MR imaging using directional diffusion weighted sequences.

A pulsed magnetic field gradient spin echo technique was used to study the brain of two volunteers and eight patients. The pulsed gradients were applied both perpendicular and parallel to the image slice. Striking changes in signal intensity were demonstrated in white matter depending on the direction in which pulsed gradients were applied. These effects enabled specific white matter tracts to be identified depending on the direction of their fibres. Abnormalities were also demonstrated in these tracts in patients with a variety of diseases, including cases where only minor abnormalities were seen with conventional, highly T2-weighted sequences. The effects were attributed to anisotropically restricted diffusion within white matter. The technique may have application in a wide range of neurological disease and result in better localisation of lesions and improved detection of disease.

AIDS Dementia Complex↗