Search PubMed⌕ Search

Biomedical subjects

K R Thulborn

Publications and source records attributed to K R Thulborn.

At least 55 records · Page 3Linked to original sources
PubMed1995

MR of the brain in mitochondrial myopathy.

PURPOSE: To determine the spectrum of MR findings in patients with mitochondrial myopathy and correlate them with central nervous system symptoms and signs. METHODS: We performed a prospective evaluation of the MR findings of eight patients with mitochondrial myopathy (three with Kearns-Sayre syndrome and five with chronic progressive external ophthalmoplegia), six of whom had central nervous system symptoms or signs (ataxia, sensorineural hearing loss, or cognitive dysfunction). RESULTS: All six patients with neurologic symptoms or signs had multiple abnormal MR findings, whereas patients without neurologic symptoms had either normal MR findings (one patient) or the solitary finding of cortical atrophy (one patient). Abnormal MR findings consisted of cerebral cortical atrophy (seven patients), cerebellar atrophy (six patients), and hyperintense signal abnormalities on T2-weighted images within the cerebral white matter (three patients), cerebellar white matter (one patient), basal ganglia (three patients), brain stem (one patient), and thalamus (one patient). In two patients, the cerebral white matter signal abnormalities were primarily peripheral and involved the arcuate fibers. All patients with ataxia had abnormal cerebellar findings on MR imaging, but there was poor correlation between other neurologic features and MR findings. CONCLUSIONS: Cerebral and cerebellar atrophy are the most common MR findings in Kearns-Sayre syndrome and chronic progressive external ophthalmoplegia. White matter and deep gray nuclei abnormalities, presumed to result from the diffuse spongiform encephalopathy reported in these patients, can also be seen. Patients with abnormal neurologic findings typically have multiple abnormalities on MR imaging, which frequently do not correlate with specific symptoms.

Adult↗
PubMed1994

Quantitative in vivo tissue sodium concentration maps: the effects of biexponential relaxation.

The biexponential relaxation behavior of the sodium nucleus affects the accuracy of quantitative measurement of in vivo tissue sodium concentration (TSC). Theoretical analysis and in vivo experimental results are used to demonstrate the extent of the large bias in the measured TSC that arises when the relaxation behavior in vivo differs significantly from that of the calibration standards which is when a significant fraction of the total sodium signal decays with a relaxation time much shorter than the echo time (TE) used for imaging. This bias can be as large as 20% for measurements of TSC in a normal rat brain with TE = 2 ms. Our findings indicate that shortening the echo time (TE < 0.5 ms) by projection imaging is a reliable means of obtaining accurate in vivo estimates for TSC using MR.

Animals↗
PubMed1993

Measurement of regional blood oxygenation and cerebral hemodynamics.

An echo planar linewidth mapping technique, Shufflebutt, has allowed temporal measurements of changes in linewidth caused by static inhomogeneities (delta LWSI) and transverse relaxation rate (delta R2) in models of hypoxia and hypercapnia. We demonstrate these changes are due to intravascular susceptibility differences/(delta chi) between the blood and tissue. Contrast agent injections at a delta chi equivalent to that of deoxygenated blood showed a twofold difference between the contrast agent and physiological anoxia values. Hypercapnia decreased both delta LWSI and delta R2 consistent with an increase in blood oxygenation. We attribute these findings to constant oxygen extraction during an increase in blood flow, resulting in less deoxygenated venous blood and thus reduced delta chi. For in vivo perturbations we found that delta R2/delta R2' approximately 0.33, a ratio much different from that measured in whole blood phantoms (delta R2/delta R2' approximately 2). This demonstrates that signal changes in these studies are produced predominantly by dephasing of extravascular protons due to field inhomogeneities produced by intravascular deoxygenated hemoglobin (deoxyHb).

Animals↗
PubMed1990

Magnetic susceptibility effects of trabecular bone on magnetic resonance imaging of bone marrow.

High-field spectroscopic studies at 5.88 tesla (T) indicate significant T2* shortening of water in suspensions of powdered bone, interpreted to be a result of magnetic susceptibility differences between bone particles and water. The authors investigated the effects of magnetic susceptibility differences between trabecular bone and water on magnetic resonance (MR) images at 0.6 T. The phantom was constructed of macerated intact trabecular human bone immersed in water. Although susceptibility-induced magnetic field inhomogeneities were detected by spectral line broadening by using an asymmetric spin-echo technique, the results show only a modest T2* shortening at this field strength. As expected, no T1 effect of trabecular bone was observed. Although susceptibility effects of trabecular bone may have a small impact on the signal intensity of MR images of bone marrow at midfield strength, the observed field strength dependence of these effects would predict significant susceptibility effects on clinical images at higher field strength.

Bone Marrow↗
PubMed1990

The role of ferritin and hemosiderin in the MR appearance of cerebral hemorrhage: a histopathologic biochemical study in rats.

A rat model of cerebral hemorrhage using stereotaxic injection of blood into the right basal ganglia was developed to investigate the influence of iron metabolism on the appearance of cerebral hemorrhage on MR images. Images of in vitro fixed brain sections stained specifically for different iron-storage substances, ferritin and hemosiderin, created by digitization of the pathology sections using an Eikonix CCD camera, were compared with the in vivo MR images of late-phase hematomas. Areas of the pathologic and MR features of the lesions were quantitatively correlated. The single-slice MR images were obtained with the use of T1- and T2-weighted spin-echo pulse sequences, as well as T2-weighted spin-echo pulse sequences in which the 180 degrees refocusing pulse was offset from the center of the echo time; this was termed an asymmetric spin-echo pulse sequence. The symmetric and asymmetric T2-weighted images allowed the calculation of line-width images, which emphasize line broadening from intravoxel magnetic field inhomogeneities that arise from the presence of iron-containing substances. From biochemical and histochemical staining, we conclude that at least two iron-storage substances are present in the late phase of resolving cerebral hematomas. Ferritin has a wider distribution than hemosiderin, showing a similar distribution to the MR signal changes of the calculated line-width images. Line-width mapping is a sensitive means of detecting magnetic field inhomogeneities caused by the magnetic susceptibility differences introduced by the aggregation of these iron-storage substances.

Animals↗
PubMed1984

Phosphorus-31 nuclear magnetic resonance studies of pig adrenal glands.

We have used phosphorus-31 nuclear magnetic resonance to study the secretion of adenosine 5'-triphosphate (ATP) from the medulla of perfused pig adrenal glands. The resonances of the nucleotide pools in the chromaffin granules and cytoplasm are clearly resolved and therefore the intragranular and cytoplasmic processes involving ATP can be monitored simultaneously in the gland during secretion. Secretion of nucleotide during a 3 h continuous stimulation by infusion of acetylcholine chloride was monitored by the decrease in intensity of the intragranular ATP resonances. Up to 40% of the total intragranular nucleotide was released under these conditions. The rate of secretion decreased with duration of stimulation. No significant changes in the steady-state levels of cytoplasmic ATP or in oxygen consumption were observed. The intragranular pH in ischaemic glands was 5.52 + 0.15, while in glands which had been perfused until their cytoplasmic nucleotide levels had recovered, the intragranular pH was 5.76 +/- 0.16. These results provide the first estimate of the internal pH of the chromaffin granules in intact perfused adrenal glands and show that no net acidification occurs in the presence of cytoplasmic ATP. However, the isolated chromaffin granule possesses a proton-pumping adenosine 5'-triphosphatase which, in the presence of a permeant counter-ion, such as chloride, acidifies the granule interior. It is, therefore, suggested that in the intact cell, the cytoplasmic concentration of permeant counter-ions is too low to allow electrically neutral proton accumulation in the granules.

Acetylcholine↗
PubMed1982

The effects of cholesterol on the time-resolved emission anisotropy of 12-(9-anthroyloxy)stearic acid in dipalmitoylphosphatidylcholine bilayers.

The time-resolved fluorescence emission anisotropy of 12-(9-anthroyloxy)stearic acid (12-AS) and 1,6-diphenyl-1,3,5-hexatriene (DPH) have been measured in dipalmitoylphosphatidylcholine liposomes in the presence and absence of 40 mol% cholesterol at temperatures above and below the phase transition temperature (41 degrees C). By using a synchronously-pumped mode-locked frequency-doubled dye laser and single photon counting detection with an excitation response function of 300 picosecond, rotational correlation times down to less than 1 nanosecond could be resolved. Whereas DPH showed only small changes in the limiting anisotropy on the addition of cholesterol, 12-AS showed significant increases in this parameter with the effect being potentiated at higher temperatures. This difference in behaviour has been attributed to a fluorophore-cholesterol interaction that resulted in a change in the fluorophore geometry. Not only do DPH and 12-AS sense different depolarizing rotations due to the different directions of their emission dipoles but also differ in their lipid interactions which alter their limiting anisotropies. The implication is that the comparison of steady-state anisotropy measurements between chemically identical fluorophores in different lipid environments may be complicated by molecular distortions that change the motions to which the steady-state fluorescence parameters will be sensitive.

Cholesterol↗
PubMed1982

Oxygenation dependence of the transverse relaxation time of water protons in whole blood at high field.

At high and medium magnetic field, the transverse NMR relaxation rate (T-1(2)) of water proteins in blood is determined predominantly by the oxygenation state of haemoglobin. T-1(2) depends quadratically on the field strength and on the proportion of haemoglobin that is deoxygenated. Deoxygenation increases the volume magnetic susceptibility within the erythrocytes and thus creates local field gradients around these cells. From volume susceptibility measurements and the dependence of T-1(2) on the pulse rate in the Carr-Purcell-Meiboom-Gill experiment, we show that the increase in T-1(2) with increasing blood deoxygenation arises from diffusion of water through these field gradients.

Animals↗
PubMed1982

A 31P nuclear magnetic resonance in vivo study of cerebral ischaemia in the gerbil.

We have used the noninvasive method of 31phosphorus nuclear magnetic resonance (31P NMR) in vivo to follow changes in phosphorous metabolite concentrations and the intracellular pH in the right and left hemispheres and in the cerebellum of gerbil brains after the occlusion of the right carotid artery. Spatial resolution over the brain was possible using surface coils. Ligation, which is know to cause ischaemia in this species in the ipsilateral hemisphere, resulted in the diminution of phosphocreatine and adenine nucleotides and a decrease in tissue pH. Less acidification occurred in the contralateral hemisphere and in the cerebellum. The high-energy metabolite concentrations, phosphocreatine and adenosine triphosphate (ATP), declined in unison in the ischaemic region, in marked contrast to the sequence of events in skeletal muscle, in which phosphocreatine buffers against an immediate fall in ATP concentration. In a separate series of gerbils, 31P NMR spectra were followed for exactly 1 h after carotid ligation. The animals were then sacrificed and brain grey matter specific gravity was rapidly measured to assess the development of oedema. There was a clear correlation between abnormality of spectra and the presence of oedema. It cannot, however, be confidently asserted that a normal spectrum is never seen in oedematous gerbil brains. 31P NMR spectra specific gravity and histological changes shown by light microscopy have been correlated and show that useful signals are received from a depth of at least 4 mm or more from the 10-mm diameter coil.

Adenine Nucleotides↗
PubMed1980

Perturbations to lipid bilayers by spectroscopic probes as determined by dielectric measurements.

Dielectric measurements on lecithin/cholesterol bimolecular lipid membranes have indicated that the series of extrinsic fluorescent probe molecules, the n-(9-anthroyloxy) fatty acids, cause significant perturbation to the bilayer structure at concentrations equivalent to those used in fluorescence experiments (0.1 mol%). Perturbations were observed in the capacitance and conductance of the electrically distinct substructural regions of the bilayer that were consistent with the putative location of the probe molecules. Inclusion of stearic acid decreased the thickness of the hydrocarbon region of the membrane, presumably by expanding the average surface area per unit membrane mass, and also significantly disrupted the surface regions. The attachment of the anthroyloxy moiety to position 2 of a fatty acid accentuated both these effects. Attachment at position 12 had the reverse effect by increasing the volume of the hydrocarbon region without further disturbance of the surface organisation. The 9-positioned probe had an intermediate effect. The degree of perturbation by the 2-positioned probe was dependent on the probe concentration within the range (probe:lipid) 1:1000 to 1:10 000. The technique therefore detects perturbation of structure at probe levels which are lower than those commonly used in fluorescence-labelling experiments.

Alkanes↗
PubMed1979

The use of n-(9-anthroyloxy) fatty acids to determine fluidity and polarity gradients in phospholipid bilayers.

A set of n-(9-anthroyloxy) fatty acid probes (n = 2, 6, 9, 12) have been used to examine gradients in fluorescence polarization, lifetime (tau F), relative quantum yield (phi rel) and positions of emission maxima (lambda max) through bilayers composed of synthetic phospholipids. The fluorophores of these probes report the environment at a graded series of depths from the surface to the centre of the bilayer structure. 1. Polarizations decrease as the fluorophore is moved deeper into the bilayer indicating greater rotational motion of the fluorophore in the hydrocarbon core of the bilayer. 2. The different responses of the probe diphenylhexatriene and the anthroyloxy fatty acids to the action of cholesterol on lipid bilayers are discussed in terms of the orientation of these probes in the bilayer and the types of anisotropic rotational motions which result in depolarization of fluorescence. 3. Stearic acid derivatives which have the fluorophore in the 6-, 9- and 12-positions along the acyl chain have a similar response to solvent polarity as measured by values of lambda max and phi rel in a variety of organic solvents. 4. The position of the emission maximum has little dependence on solvent viscosity, but viscosity does change the degree of vibrational structure seen in the emission spectrum. The vibrational structure itself may be used as an indication of the 'mciroviscosity' gradient in the transverse plane of the bilayer. 5. Values of lambda max, tau F and phi rel indicate that a gradient of polarity exists from the surface to the centre of the bilayer. For dipalmitoyl phosphatidylcholine in the crystalline phase, cholesterol acts to make this polarity gradient shallower.

Fatty Acids↗
PubMed1979

Comparison of fluorescence energy transfer and quenching methods to establish the position and orientation of components within the transverse plane of the lipid bilayer. Application to the gramicidin A--bilayer interaction.

Fluorescence quenching and resonance energy transfer methods have been used to investigate the position of fluorophores in the lateral and transverse planes of the lipid bilayer. A series of n-(9-anthroyloxy) fatty acids (n = 2, 6, 9, and 12) have been used as energy-transfer acceptors so that apparent transfer distances from a membrane-bound donor (N-stearoyltryptophan) have a transverse as well as a lateral component. Both theory and experiment show that the energy-transfer method is not precise enough to discriminate between the positions of the fluorophores in the transverse plane of the bilayer. The n-(9-anthroyloxy) fatty acids are also susceptible to quenching by the indole moiety of tryptophan. The relative quenching efficiency can provide a semiquantitative measure of the position of quenching molecules in the lipid bilayer. The quenching techniques are applied to the determination of the orientation of gramicidin A in lipid bilayers. The tryptophan residues of gramicidin appear to be located near the membrane surface in agreement with the head-to-head dimeric structure proposed by D. W. Urry et al. [(1971) Proc. Natl. Acad. Sci. U.S.A. 68, 672--676].

Energy Transfer↗
PubMed1979

Leghaemoglobin from Trifolium subterraneum. Purification and characterization.

Leghaemoglobin from the subclover, Trifolium subterraneum cultivar Woogenellup, has been fractionated into at least four electrophoretically distinct components using the ion-exchange chromatographic procedure described by Appleby et al. (Appebly, C.A., Nicola, N.A., Hurrell, J.G.R. and Leach, S.J. (1975) Biochemistry 14, 4444--4450) for soybean leghaemoglobins. Unlike those of soybean, the subclover leghaemoglobins showed no evidence of autoxidation under identical isolation procedures, implying that these proteins have an unusually stable ferrous oxidation state. Circular dichroism in the far-ultraviolet (200--240 nm) indicated a high helicity (approx. 70%) as has been reported for other species of leghaemoglobins. However, circular dichroism in the near-ultraviolet region (240--300 nm) indicated that the haem-protein interactions may be considerably different in the subclover leghaemoglobins and this may explain their atypical resistance to autoxidation and the absence of nicotinate binding in these proteins.

Binding Sites↗
PubMed1979

An assessment of the fluidity gradient of the lipid bilayer as determined by a set of n-(9-anthroyloxy) fatty acids (n = 2, 6, 9, 12, 16).

The rotational behavior of a set of n-(9-anthroyloxy) fatty acid fluorescent probes is examined in two liquid paraffins and in liposomes composed of dipalmitoyl phosphatidylcholine. As has been observed with other membrane fluorescent probes (Hare, F., and Lussan, C. (1977) Biochim. Biophys. Acta 467, 262-272), the degree of fluorescence depolarization for a given solvent viscosity is dependent on the solvent standard employed. In addition, when the anthroyloxy group is in the terminal position of the acyl chain, it has more rotational freedom than when it is conjugated to positions 6, 9, or 12 where the rotational motion of the fluorophore is similar. When incorporated into lipid bilayers, values of fluorescence polarization reflect the gradient of "fluidity" which extends from the surface to the center of the membrane. The nature of this polarization gradient is discussed in relation to the intrinsic differences between the probes and the anisotropic rotations responsible for depolarization.

Anthracenes↗
PubMed1978

Properties and the locations of a set of fluorescent probes sensitive to the fluidity gradient of the lipid bilayer.

The synthesis and properties of a set of four fluorescent probes (n-(9-anthroyloxy) fatty acids, n = 2, 6, 9, 12) sensitive to the fluidity gradient of the lipid bilayer are described. Fluorescent quenching experiments show that the probes locate at a graded series of depths in the bilayer. A fifth probe, methyl-9-anthroate, locates near the bilayer centre. As an example of their application, the probes are used to study the phase transitions of dipalmitoyl phosphatidyl-choline. Changes in the rotational relaxation times of the probes across the transitions are more pronounced at the centre of the bilayer than at the surface.

Anthracenes↗