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Biomedical subjects

K Ugurbil

Publications and source records attributed to K Ugurbil.

At least 91 records · Page 5Linked to original sources
PubMed1992

Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging.

We report that visual stimulation produces an easily detectable (5-20%) transient increase in the intensity of water proton magnetic resonance signals in human primary visual cortex in gradient echo images at 4-T magnetic-field strength. The observed changes predominantly occur in areas containing gray matter and can be used to produce high-spatial-resolution functional brain maps in humans. Reducing the image-acquisition echo time from 40 msec to 8 msec reduces the amplitude of the fractional signal change, suggesting that it is produced by a change in apparent transverse relaxation time T*2. The amplitude, sign, and echo-time dependence of these intrinsic signal changes are consistent with the idea that neural activation increases regional cerebral blood flow and concomitantly increases venous-blood oxygenation.

Brain Chemistry↗
PubMed1992

Functional brain mapping using magnetic resonance imaging. Signal changes accompanying visual stimulation.

Easily detectable (5%-20%) transient increases in the intensity of water proton magnetic resonance (MR) signals in human primary visual cortex were observed during visual stimulation in gradient echo images at 4-T field strength. The signal intensity increases were predominantly restricted to areas containing gray matter and were used to produce high-spatial-resolution human functional brain maps. Time dependence of the functional brain maps also was monitored during visual stimulation using images acquired every approximately 5 seconds; these images with high spatial and temporal resolution demonstrated that photic stimulation first resulted in signal increases in a large area of the visual cortex followed by a reduction in the size of the area, and that signal intensity increases in the gray matter were time dependent. Reducing the image acquisition echo times reduced the amplitude of the fractional signal change, suggesting that it is produced by a change in T2 or T2*. The amplitude, sign, and echo time dependence of these intrinsic signal changes are consistent with the idea that neural activation increases regional cerebral with the idea that neural activation increases regional cerebral blood flow (rCBF) with a concomitant increase in venous blood oxygenation.

Brain Mapping↗
PubMed1991

Ischemic contracture begins when anaerobic glycolysis stops: a 31P-NMR study of isolated rat hearts.

The relationships among myocardial ATP, intracellular pH, and ischemic contracture in Langendorff-perfused rat hearts were investigated by 31P nuclear magnetic resonance spectroscopy during total global normothermic ischemia while the left ventricular pressure was recorded continuously via an intraventricular balloon. Glucose-perfused hearts (n = 63) were divided into five groups based on the time of onset of contracture (TOC), and three other groups of hearts were treated to vary the ischemic glycogen availability. ATP levels, which showed no evidence of accelerated ATP depletion during contracture, were significant and variable at TOC. Intracellular pH initially declined and then leveled off at TOC, with lower final pH in hearts with later TOC. We conclude that contracture began when anaerobic glycolysis (and thus glycolytic ATP synthesis) stopped. These results, though consistent with the concept that ischemic contracture in normal hearts results from rigor bond formation due to low ATP levels at the myofibrils, suggest that TOC is more closely related to glycolytic ATP production than to total cellular ATP content, thus providing evidence of some degree of subcellular compartmentation or metabolite channeling. In glycolytically inhibited hearts, the quite early contracture may have a Ca2+ component.

Anaerobiosis↗
PubMed1988

ATP synthesis kinetics and mitochondrial function in the postischemic myocardium as studied by 31P NMR.

The effects of ischemia on mitochondrial function and the unidirectional rate of ATP synthesis (Pi----ATP rate) were studied using a Langendorff-perfused heart preparation and 31P NMR spectroscopy. There was significant postischemic depression of mechanical function assessed as the heart rate pressure product, and the myocardial oxygen consumption rate at a given rate pressure product was elevated. Experiments performed on glucose- and pyruvate-perfused hearts demonstrated the presence of a large contribution to the unidirectional Pi----ATP rate catalyzed by glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase. This rate was much greater than the maximal glucose utilization rate in the myocardium, demonstrating that the glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase reactions are near equilibrium both before and after ischemia. In the pyruvate-perfused postischemic hearts, the glycolytic contribution was eliminated and the net rate of ATP synthesis by oxidative phosphorylation was measurable. Despite the reduced mechanical function and increased myocardial oxygen consumption rate, the ratio of the net rate of ATP synthesis by oxidative phosphorylation to oxygen consumption rate (the P:O ratio) was not altered subsequent to ischemia (2.34 +/- 0.12 and 2.36 +/- 0.09 in normal and postischemic hearts, respectively). Therefore, mitochondrial uncoupling cannot be the cause of postischemic depression in mechanical function; instead, the data suggest the existence of ischemia-induced inefficiency in ATP utilization.

Adenosine Triphosphate↗
PubMed1988

Substrate effects in the post-ischemic myocardium.

A study was undertaken to examine the effects of glucose versus pyruvate as the sole substrate following severe myocardial ischemia. Glycolysis usually contributes only a small amount to total ATP production and may be rate limiting in providing tricarboxylic acid (TCA) cycle substrates. Consequently, pyruvate may be a more effective substrate by bypassing glycolysis to feed directly to the TCA cycle and oxidative phosphorylation. Isolated rat hearts were studied in a retrograde (Langendorff) perfusion apparatus while in an NMR spectrometer. Rate pressure product (RPP), myocardial oxygen consumption (MVO2), and the unidirectional Pi----ATP rate were measured in control and postischemic hearts with or without the inotrope dobutamine. The undirectional Pi----ATP rate was higher in the glucose than the pyruvate hearts and the difference increased further postischemia. This increase over that of the pyruvate hearts has been attributed to a glycolytic component of ATP metabolism. Oxygen consumption was higher in pyruvate hearts at equivalent levels of performance. It thus appears that the glycolysis rate is significant and may be elevated following severe myocardial ischemia. Perfusion with pyruvate requires increased rates of oxidative phosphorylation to make up for the loss of glycolytically produced ATP. Optimal postischemic substrate delivery may require several compounds, one of which should be glucose.

Adenosine Triphosphate↗
PubMed1988

31P nuclear magnetic resonance studies of effects of some chlorophenols on Escherichia coli and a pentachlorophenol-degrading bacterium.

A Flavobacterium sp. that mineralizes pentachlorophenol degrades some, but not all, of the other chlorinated phenols. Whole-cell 31P nuclear magnetic resonance was used to compare and observe transmembrane pH gradients and nucleotide pools in the Flavobacterium sp. and Escherichia coli after pentachlorophenol and 3,4,5-trichlorophenol were added to the cell suspensions. The data suggest that those chlorinated phenols which are not degraded by the Flavobacterium sp. may be resistant to degradation because they act as proton dissipators.

Biotransformation↗
PubMed1986

31P NMR measurement of ATP synthesis rate in perfused intact rat hearts.

Using 31P NMR and the saturation-transfer method, the unidirectional rate of ATP synthesis was measured in isolated, Langendorff-perfused, isovolumic rat hearts operating at a rate pressure product of 25.6 +/- 2.5 (SE) X 10(3) mmHg X min-1 and consuming O2 at a rate of 35 +/- 2 mumol O2 X min-1 X (g dry wt)-1, at 37 degrees C. This rate was 7.2 +/- 0.9 mumol X s-1 X (g dry wt)-1 and was related to the rate of oxygen atom consumption by a ratio of 6.3 +/- 0.9. These data show that in the intact heart the unidirectional rate of ATP synthesis exceeds the net rate of ATP synthesis and consumption by approximately a factor of 2.

Adenosine Triphosphate↗
PubMed1986

Studies of anaerobic and aerobic glycolysis in Saccharomyces cerevisiae.

Glucose metabolism was followed in suspensions of Saccharomyces cerevisiae by using 13C NMR and 14C radioactive labeling techniques and by Warburg manometer experiments. These experiments were performed for cells grown with various carbon sources in the growth medium, so as to evaluate the effect of catabolite repression. The rate of glucose utilization was most conveniently determined by the 13C NMR experiments, which measured the concentration of [1-13C]glucose, whereas the distribution of end products was determined from the 13C and the 14C experiments. By combining these measurements the flows into the various pathways that contribute to glucose catabolism were estimated, and the effect of oxygen upon glucose catabolism was evaluated. From these measurements, the Pasteur quotient (PQ) for glucose catabolism was calculated to be 2.95 for acetate-grown cells and 1.89 for cells grown on glucose into saturation. The Warburg experiments provided an independent estimate of glucose catabolism. The PQ estimated from Warburg experiments was 2.9 for acetate-grown cells in excellent agreement with the labeled carbon experiments and 4.6 for cells grown into saturation, which did not agree. Possible explanations of these differences are discussed. From these data an estimate is obtained of the net flow through the Embden-Meyerhof-Parnas pathway. The backward flow through fructose-1,6-bisphosphatase (Fru-1,6-P2-ase) was calculated from the "scrambling" of the 13C label of [1-13C]glucose into the C1 and C6 positions of trehalose. Combining these data allowed us to calculate the net flux through phosphofructokinase (PFK). For acetate-grown cells we found that the relative flow through PFK is a factor of 1.7 faster anaerobically than aerobically.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerobiosis↗
PubMed1986

31P and 13C NMR studies of intermediates of aerobic and anaerobic glycolysis in Saccharomyces cerevisiae.

The levels of intermediates of aerobic and anaerobic glycolysis were determined in perchloric acid extracts prepared from glycolyzing suspensions of Saccharomyces cerevisiae by 31P and 13C NMR spectroscopy. From 31P NMR measurements a small increase in the level of nucleoside triphosphates was found in derepressed cells upon oxygenation, while the ratio of nucleoside diphosphates to nucleoside triphosphates was a factor of 3 lower aerobically. Combined with the previous observation that the level of intracellular Pi is lower by a factor of 3 aerobically, this leads to the conclusion that the phosphate potential [NTP]/([NDP][Pi]) is lower by an order of magnitude during anaerobic glycolysis than during aerobic glycolysis. There was no correlation between the level of glucose 6-phosphate and the rate of glucose utilization. We used 13C NMR to determine the scrambling of the 13C label from C1 to C6 in fructose 1,6-bisphosphate (Fru-P2). There was more scrambling of the label during aerobic than during anaerobic glycolysis. Since the level of Fru-P2 did not change much upon oxygenation, this suggests that in aerobic glycolysis there is control of at least one enzyme in the lower part of the Embden-Meyerhof-Parnas pathway, below Fru-P2, which gives the 13C level more time to equilibrate between C1 and C6 of Fru-P2. Previous 13C NMR measurements of glucose utilization rates had shown a 2-fold reduction upon oxygenation, reflecting control in the early stages of the pathway.

Aerobiosis↗
PubMed1984

Histamine uptake in pig platelets and isolated dense granules.

Histamine, a major constituent of the amine-storage organelles in pig platelets, is taken up by intact platelets in only trace amounts under conditions where 70% of 14C-serotonin is accumulated. Thrombin caused the release of 70-90% of endogenous histamine but only 5-10% of the newly absorbed 3H-amine; however, after 18 hr 30% of the 3H-amine could be specifically released by thrombin. Isolated storage organelles accumulated histamine in a reserpine-sensitive, ATP-dependent manner but at a rate 80-100-fold less than serotonin uptake. Incubation of intact platelets with 1 mM serotonin until amine uptake was saturated caused no changes in platelet histamine content. Similarly, loading of isolated storage organelles with 1 mM histamine or 1 mM serotonin did not affect the levels of the other amine. These results suggested that the storage of each amine is independent of the other. Histidine decarboxylase was not detected in platelet lysates. Since platelets have a short half-life (1-2 weeks) and pig plasma levels of histamine are higher than in other animals, it is concluded that most of the histamine in the storage organelles is probably accumulated in the platelet precursor, the megakaryocyte, either by slow uptake or by synthesis.

Animals↗
PubMed1984

High resolution proton NMR studies of perfused rat hearts.

High resolution 1H NMR spectra of perfused rat hearts have been obtained under normoxic, ischemic and hypoxic conditions. Several myocardial metabolites including taurine, carnitine, lactate and tissue glycerides are detected in the 1H NMR spectra. Changes in oxygen availability induce perturbations in the levels of some metabolites, in particular, lactate. Experiments with fasted rats and with substrate-free perfusion suggest that the glycerides detected in 1H spectra are metabolically mobilizable but have a slow rate of turnover. These results demonstrate that utility of 1H NMR in monitoring myocardial metabolism.

Animals↗
PubMed1983

Observation of a second phosphate pool in the perfused heart by 31P NMR; is this the mitochondrial phosphate?

We report here our observations on perfused rat hearts using 31P NMR which show that inorganic phosphate (Pi) is located in two regions of differing pH. From the chemical shifts of the Pi signals and their behaviour under various stimuli we identify one signal (pH 7.0) as coming from the cytosol and suggest that the other (pH 7.38) comes from the mitochondrial matrix space.

Animals↗
PubMed1982

Phosphorus-31 nuclear magnetic resonance studies of bioenergetics in wild-type and adenosinetriphosphatase(1-) Escherichia coli cells.

By use of 31P NMR, the transmembrane pH gradient (delta pH) and the intracellular levels of phosphorylated metabolites were measured in aerobic suspensions of wild-type Escherichia coli cells in the presence and absence of the adenosinetriphosphatase (ATPase) inhibitor dicyclohexylcarbodiimide (DCCD); the same parameters were also determined in E. coli mutants deficient in ATPase activity under both anaerobic and aerobic conditions. A method is described by which dense suspensions of E. coli cells (approximately 3 X 10(11) cells/mL) were oxygenated so that steady-state O2 levels in the suspensions were far greater than the Km for O2 consumption. Under these conditions, in wild-type MRE600 cells, the intracellular concentrations of PI, NTP, and NDP were measured to be 3.0 +/- 1.5, 8 +/- 1, and 1.2 +/- 1 mM, respectively, while the intracellular pH was approximately 7.5 over the external pH range studied (6 to approximately 7.0). Upon treatment with DCCD, the intracellular NTP level was drastically reduced and intracellular Pi concentration increased in respiring wild-type cells; in the same cells, however, DCCD did not affect the intracellular pH and the delta pH. During respiration in the presence of lactate, ATPase- cells established a delta pH but failed to synthesize any detectable levels of NTP. Conversely, ATPase- cells accumulated high levels of NTP but did not generate a delta pH during glycolysis under anaerobic conditions. These results are in complete agreement with the generally accepted chemiosmotic hypothesis. 31P NMR data on intact ATPase- NR70 cells were in agreement with the previously proposed [Rosen, B. P., Brey, R., & Hasan, S. (1978) J. Bacteriol. 134, 1030] existence of a proton leak in this strain which is sealed by DCCD or by spontaneous mutation into strain NR71. However, the NMR data also indicated that other major differences exist between NR71 and NR70 cells.

Adenosine Triphosphatases↗
PubMed1982

NMR chemical shift imaging in three dimensions.

A method for obtaining the three-dimensional distribution of chemical shifts in a spatially inhomogeneous sample using Fourier transform NMR is presented. The method uses a sequence of pulsed field gradients to measure the Fourier transform of the desired distribution on a rectangular grid in (k,t) space. Simple Fourier inversion then recovers the original distribution. An estimated signal/noise ratio of 20 in 10 min is obtained for an "image" of the distribution of a 10 mM phosphorylated metabolite in the human head at a field of 20 kG with 2-cm resolution.

Fourier Analysis↗
PubMed1981

31P NMR studies of intracellular pH and phosphate metabolism during cell division cycle of Saccharomyces cerevisiae.

We have analyzed changes in intracellular pH and phosphate metabolism during the cell cycle of Saccharomyces cerevisiae (NCYC 239) by using high-resolution 31P NMR spectroscopy. High-density yeast cultures (2 x 10(8) cells per ml) were arrested prior to "start" by sequential glucose deprivation, after which they synchronously replicated DNA and divided after a final glucose feeding. Oxygenation of arrested cultures in the absence of glucose led to increased levels of sugar phosphates and ATP and an increase in intracellular pH. However, these conditions did not initiate cell cycle progression, indicating that energization is not used as an intracellular signal for initiation of the cell division cycle and that the cells need exogenous carbon sources for growth. Glucose refeeding initiated an alkaline intracellular pH transient only in the synchronous cultures, showing that increased intracellular pH accompanies the traversal of start. Changes in phosphate flow and utilization also were observed in the synchronous cultures. In particular, there was increased consumption of external phosphate during DNA synthesis. When external phosphate levels were low, the cells consumed their internal polyphosphate stores. This shows that, under these conditions, polyphosphate acts as a phosphate supply.

Cell Cycle↗