PubMed Health⌕ Search

Biomedical subjects

B Chance

Publications and source records attributed to B Chance.

At least 73 records · Page 4Linked to original sources
PubMed1995

Genetic disease of mitochondrial function evaluated by NMR and NIR spectroscopy of skeletal tissue.

Bioenergetic sufficiency can be quantitatively assayed by nuclear magnetic resonance spectroscopy (MRS) and on a relative basis by tissue optical spectroscopy (NIRS). Nuclear magnetic resonance measures quantitatively the fall of phosphocreatine and the rise of inorganic phosphate necessary to raise mitochondrial adenosine diphosphate and activate ATP synthesis to adequate level to meet metabolic demands. This relationship is readily demonstrated in skeletal muscle where the quality of supply and demand for ATP is observed over a wide range of aerobic exercise. Metabolic and genetic disease of mitochondria is readily detected by the rapid fall of PCR and rise of Pi during mild exercise and has been essential in the diagnosis and therapy of deficiency of cytochrome bc1 in human skeletal muscle. Insufficiencies of oxygen utilization in relation to oxygen delivery are readily measured optically by the simplest of dual wavelength spectrometers. Instead of deoxygenating hemoglobin during exercise in cases of normal bioenergetic function, a luxury perfusion or hyperoxygenation of skeletal muscles occurs in exercising the energetically deficient skeletal tissue. In this way, a simple screen for metabolic and mitochondrial disease of energy production has been established and demonstrated in a number of clinical cases. Thus, the combination of the absolute evaluations by NMR and the relative indications of light of spectroscopy (NIRS) form essential tools in detection of mitochondrial defects.

Adenosine Triphosphate↗
PubMed1995

Effects of solutes on optical properties of biological materials: models, cells, and tissues.

Perturbations of scattering background for absorbance measurements by photon diffusion techniques complicate algorithms used for determining the concentration of blood and the saturation of hemoglobin in tissues. In order to better define these perturbations, we have undertaken a study of the effect of solutes, some of physiological importance, upon the scattering of three types of model systems: a lipid vessel suspension (Intralipid), a cell suspension (Baker's yeast), and a tissue (perfused liver). A simple formula relates absorbancy change to proportional changes of the input/output separation rho and the square root of mu a and mu's in relation to a relevant model system. Thus, absorbance changes at 850 nm slopes and intercepts are measured as a function of rho; the absorption and reduced scattering coefficient, mu a and mu's, are calculated. We studied each of these cases as a function of the perturbation induced by low-molecular-weight polyhydroxy solutes, generally sugars (mannitol, fructose, sucrose, and glucose), alcohols (propanediol and methanol), and electrolytes (sodium and potassium chloride). Dilatometric studies indicate volume changes of the solvent system and afford correction factors. The slopes are approximately +/- 0.5 x 10(-4) OD/mM solute per centimeter separation of input/output per percent scatter (yeast or Intralipid) and indicate possible physiological detection of solutes in tissues in the millimolar range. The large optical effects of temperature upon the solute effect on model systems and of osmotic and perfusion pressures on the perfused liver further complicate the possibility of quantitative in vivo studies of these solutes.

Animals↗
PubMed1995

Correlation between the light scattering and the mitochondrial content of normal tissues and transplantable rodent tumors.

The development of noninvasive optical studies necessitates an understanding of the biological parameters which affect light propagation in soft tissues. In the present report, we have measured the optical properties of various normal (i.e., perfused liver, brain, skeletal muscle, white adipose tissue) and neoplastic rodent tissues (i.e., glioma, hepatoma, mammary adenocarcinoma) by using time-resolved spectroscopy. The contribution of the hemoglobin (+ myoglobin in the case of muscle) to the total light absorption at 780 nm has been determined. This contribution varies from about 25% (brain, skeletal muscle) to about 100% (white adipose tissue, 13762A mammary adenocarcinoma, 9L glioma). These results are explained by different blood volume fractions in the tissues and by the existence at 780 nm of other chromophores, such as the mitochondrial cytochrome oxidase. Secondly, the dependence of the light scattering of the tissue on both the cell and the mitochondrial content has been analyzed. The results indicate that there is no correlation between the light scattering and the DNA content, measured as an indicator of the cell number in the tissue. The scattering coefficient is proportional to both the succinate dehydrogenase activity and the mitochondrial protein content of the tissue, which are indicators of the mitochondria content of the tissue when based upon estimates of tissue wet weight.

Adipose Tissue↗
PubMed1995

Transcranial optical path length in infants by near-infrared phase-shift spectroscopy.

BACKGROUND: Near-infrared spectroscopy (NIRS) is an emerging technique for noninvasive, bedside monitoring of cerebral oxygenation and blood flow. Traditionally, it has relied on the Beer's Law relationship in which the concentration of light-absorbing oxygen-carrying pigments is proportional to their light absorbance, and inversely proportional to an optical path length (a measure of the distance traveled by photons passing through the tissue). In practice, NIRS has been based upon assumptions that mean transcranial optical path length, the average optical path length for a given patient, is constant among patients and independent of the wavelength of light used. OBJECTIVE: The objective of our study was to measure mean optical transcranial path length in infants as a step in allowing quantitation of cerebral oxygenation. METHODS: We measured mean transcranial optical path length in 34 infants, aged 1 day to 3 years, using amplitude-modulated phase-shift spectroscopy at 754 nm and 816 nm. Optical transcranial path lengths (mean +/- SEM) were 8.6 +/- 0.9 cm, 11.1 +/- 0.9 cm, and 11.3 +/- 0.9 cm at 754 nm, and 8.8 +/- 0.9 cm, 11.2 +/- 0.8 cm, and 11.1 +/- 0.9 cm at 816 nm, using emitter-detector separations of 1.8, 2.5, and 3.0 cm, respectively. Optical path length increased as emitter-detector separation, head circumference, or age increased. Variance in the ratio of mean optical path lengths at the two different wavelengths exceeded that accounted for by variation in repeated measures alone (p < 0.001), suggesting that optical path length is also not independent of wavelength. CONCLUSIONS: NIRS instrument emitter-detector geometry, subject age, head size, and wavelength used each influence optical path length. Quantitative NIRS measurements in clinical use may require concurrent measurement of both absorbance and optical path length at each wavelength, or use of newer measures that are not based upon Beer's Law assumptions.

Child, Preschool↗
PubMed1995

Chemiluminescent measurement of increased free radical formation after ischemia/reperfusion. Mechanisms of free radical formation in the liver.

It has been proposed that xanthine oxidase-derived superoxide mediates reperfusion injury in the liver; however, there is a little direct evidence to support this hypothesis. In this paper we describe a model system to directly and noninvasively measure oxyradical formation and hepatic injury in isolated perfused rat liver. Using this sensitive chemiluminescent technique, we clearly demonstrate the theorized burst in oxygen radical production upon reperfusion of previously ischemic liver, without perturbing the system with chemical luminescence enhancers. This increase in chemiluminescence (CL) upon reperfusion was diminished by the free radical scavengers trolox and ascorbate, as well as N-2-mercaptoproprionyl-glycine (MPG), thereby confirming the oxyradical nature of this signal. Additionally, superoxide dismutase and the xanthine oxidase inhibitor allopurinol, but not catalase, attenuated the reperfusion effect, providing the most direct evidence so far that XOD derived superoxide anion is formed during liver reperfusion. Hepatic injury (AST release) did not appear to relate to increased CL, supporting the notion that the oxyradical flux may serve as a signal for other events leading to tissue injury. Further studies using this sensitive chemiluminescent technique should aid in delineating the detailed mechanism(s) of reperfusion injury.

Animals↗
PubMed1995

Determination of optical properties and blood oxygenation in tissue using continuous NIR light.

In this article, we introduce a simple method to characterize optical properties and blood oxygenation in tissue using spatially resolved, steady-state reflectance. The method considers multiple source-detector separations larger than 2 cm, i.e. 20 times the optical mean free path in tissue, and makes an approximation to linearize the relationship between the separation and reflectance. Simulation results show that errors of the algorithm due to the approximation are less than 10%. Using a calibration sample, we calculate from the slope and intercept the absorption and reduced scattering coefficients, mu a and mu's, of a tissue-like solution, and experimental results confirm the usefulness of the method for quantitation of haemoglobin saturation in tissue.

Algorithms↗
PubMed1995

A dynamic phantom brain model for near-infrared spectroscopy.

This report describes the construction, fluid dynamics and optical properties of an in vitro model of the neonatal brain for testing near-infrared spectroscopy (NIRS) instruments. The brain model is a solid plastic structure containing a vascular network perfused with blood equilibrated with O2, N2 and CO2 in a closed circuit. The oxygenation state and haemoglobin concentration of the perfusate can be regulated and measured with a co-oximeter, providing a means to compare NIRS measurements of oxy-, deoxy- and total haemoglobin concentrations and haemoglobin O2 directly with a validated standard method. Fluid dynamic experiments revealed that the model's vasculature remains stable over time with minimal haemolysis. The model's optical properties were characterized by time-resolved and continuous wave NIRS between 670 and 850 nm as perfusate saturation was varied in the range 0-100%. Optical properties of the neonatal piglet brain were also determined by similar methods. No significant differences were found between the model and piglet brain in absorption coefficients, reduced scattering coefficients and optical pathlengths, indicating that the model optically simulates the piglet brain over a wide range of oxygenation states. These results demonstrate the potential utility of this dynamic phantom brain for testing NIRS instruments for accuracy and reliability.

Animals↗
PubMed1995

A new application for near-infrared spectroscopy: detection of delayed intracranial hematomas after head injury.

Clinical studies have documented the importance of secondary brain insults in determining neurologic outcome after head injury. Delayed intracranial hematomas are one of the most easily remediable causes of secondary injury if identified early, but can cause significant disability or death if not promptly recognized and treated. Early identification and treatment of these lesions that appear or enlarge after the initial CT scan may improve neurological outcome. Serial examinations using near-infrared spectroscopy (NIRS) to detect the development of delayed hematomas were obtained in 167 patients. The difference in absorbance of light (deltaOD) at 760 nm between the normal and the hematoma side was measured serially during the first 3 days after injury. Twenty-seven (16%) of the patients developed some type of late hematoma: an intracerebral hematoma in 8 patients, an extracerebral hematoma in 6 patients, and a postoperative hematoma in 13 patients. Eighteen of the delayed hematomas caused significant mass effect and required surgical evacuation. The hematomas appeared between 2 and 72 h after admission. In 24 of the 27 patients, a significant increase (>0.3) in the deltaOD occurred prior to an increase in intracranial pressure or a change in the neurological examination, or a change on CT scan. Early diagnosis using MRS may allow early treatment and reduce secondary injury caused by delayed hematomas.

Cerebral Hemorrhage↗
PubMed1995

Insulin, ketone bodies, and mitochondrial energy transduction.

Addition of insulin or a physiological ratio of ketone bodies to buffer with 10 mM glucose increased efficiency (hydraulic work/energy from O2 consumed) of working rat heart by 25%, and the two in combination increased efficiency by 36%. These additions increased the content of acetyl CoA by 9- to 18-fold, increased the contents of metabolites of the first third of the tricarboxylic acid (TCA) cycle 2- to 5-fold, and decreased succinate, oxaloacetate, and aspartate 2- to 3-fold. Succinyl CoA, fumarate, and malate were essentially unchanged. The changes in content of TCA metabolites resulted from a reduction of the free mitochondrial NAD couple by 2- to 10-fold and oxidation of the mitochondrial coenzyme Q couple by 2- to 4-fold. Cytosolic pH, measured using 31P-NMR spectra, was invariant at about 7.0. The total intracellular bicarbonate indicated an increase in mitochondrial pH from 7.1 with glucose to 7.2, 7.5 and 7.4 with insulin, ketones, and the combination, respectively. The decrease in Eh7 of the mitochondrial NAD couple, Eh7NAD+/NADH, from -280 to -300 mV and the increase in Eh7 of the coenzyme Q couple, Eh7Q/QH2, from -4 to +12 mV was equivalent to an increase from -53 kJ to -60 kJ/2 mol e in the reaction catalyzed by the mitochondrial NADH dehydrogenase multienzyme complex (EC 1.6.5.3). The increase in the redox energy of the mitochondrial cofactor couples paralleled the increase in the free energy of cytosolic ATP hydrolysis, delta GATP. The potential of the mitochondrial relative to the cytosolic phases, Emito/cyto, calculated from delta GATP and delta pH on the assumption of a 4 H+ transfer for each ATP synthesized, was -143 mV during perfusion with glucose or glucose plus insulin, and decreased to -120 mV on addition of ketones. Viewed in this light, the moderate ketosis characteristic of prolonged fasting or type II diabetes appears to be an elegant compensation for the defects in mitochondrial energy transduction associated with acute insulin deficiency or mitochondrial senescence.

Animals↗
PubMed1995

Theo's laboratory.

Explore the source record for details and available documents.

History, 20th Century↗
PubMed1995

Near-infrared measurement of cerebral oxygenation. Correlation with electroencephalographic ischemia during ventricular fibrillation.

BACKGROUND: The application of phase-modulated near-infrared techniques for measurement of the oxygen saturation of cerebral tissue requires both validation by conventional measures of cerebral oxygenation and determination of normal and abnormal values. This study was undertaken to validate phase-modulated near-infrared measurements of cerebral oxygen saturation by comparing them with electroencephalographic evidence of cerebral ischemia during implantation of cardioverting defibrillators. This comparison also yields an estimate of the ischemic threshold as measured with near-infrared techniques. METHODS: Electroencephalograms and near-infrared measurements were performed during 85 episodes of ventricular fibrillation in ten patients. Light at 754, 785, and 816 nm was modulated at 200 MHz, transmitted through the skull, and the path lengths of the reflected light were determined by measuring the phase shifts. The electroencephalogram was inspected for changes during the hypotension associated with the arrhythmia and the oxygen saturation was calculated from the near-infrared path lengths. Changes in oxygen saturation were then compared with electroencephalographic evidence of cerebral ischemia. RESULTS: The mean saturation before fibrillation was 56.5% +/- 1.2 (SEM). In 40 (47%) of the events, electroencephalographic evidence of ischemia was observed. Such changes were related to the minimum saturation observed during ventricular fibrillation (44% +/- 2.5 vs. 56% +/- 1.9 in the absence of electroencephalographic changes; P < 0.001). The ischemic threshold was estimated to be 47% saturation. The sensitivity of this technique was estimated to be 0.6, the specificity 0.84, and the predictive accuracy 0.73. CONCLUSIONS: Near-infrared measurements reflect changes in cerebral oxygenation as indicated by electroencephalographic evidence of cerebral ischemia.

Aged↗
PubMed1995

Influence of blood vessels on the measurement of hemoglobin oxygenation as determined by time-resolved reflectance spectroscopy.

We report the development of a heterogeneous resin-tube model to study the influence of blood vessels on the apparent absorption of the system, mu a(sys), using a time-resolved technique. The experimental results show that mu a(sys) depends on the absorption inside the tubes, mu a(tube), tube diameters, and tube-to-sample volume ratios. A mathematical expression relating mu a(sys) and mu a(tube) is derived based on the experimental results and is verified by time-resolved Monte Carlo simulations for heterogeneous models. This analytical formula predicts that the apparent absorption coefficient measured on a biological organ is a volume-weighted sum of the absorption coefficients of different absorbing components. We present some apparent absorption coefficients measured in vivo in animals and humans and discuss improved algorithms that calculate the hemoglobin saturation by including background-tissue absorption and blood vessel distribution.

Blood Vessels↗
PubMed1995

Effects of hypercapnia on ECoG and oxidative metabolism in neonatal dog brain.

The effects of hypercapnia on cerebral electrical activity and mitochondrial oxidative phosphorylation were studied in the anesthetized neonatal dog by using the electrocorticogram (ECoG) and 31P-magnetic resonance spectroscopy. Three levels of hypercapnia with arterial PCO2 values of approximately 70, 100, and 140 Torr reduced the intracellular pH of the brain from 7.11 to 6.99, 6.87, and 6.76, respectively. These levels of hypercapnia also reduced ADP concentration ([ADP]) from 21.5 to 18.1, 14.8, and 12.9 microM as well as the average ECoG power output by 20, 30, and 40%. A Michaelis-Menten relationship for the mitochondrial respiratory enzymes was fitted with [ADP] and the change in the average ECoG. The result suggests that mitochondrial respiration is regulated by [ADP] and that the in vivo Michaelis-Menten constant for ADP was 21 microM, a value close to the in vitro value. The mitochondrial maximal reaction velocity was reduced by only 10% during hypercapnia and showed no relationship with the degree of acidosis, suggesting that mitochondrial respiratory enzymes are not responsible for the inhibition of the brain electrical activity.

Adenosine Diphosphate↗
PubMed1995

Early detection of delayed traumatic intracranial hematomas using near-infrared spectroscopy.

Delayed intracranial hematomas are an important treatable cause of secondary brain injury in patients with head trauma. Early identification and treatment of these lesions, which appear or enlarge after the initial computerized tomography (CT) scan, may improve neurological outcome. Serial examinations using near-infrared spectroscopy (NIRS) to detect the development of delayed hematomas were performed in 167 patients. The difference in absorbance of light (delta OD) at 760 nm between the normal and the hematoma side was measured serially during the first 3 days after injury. Twenty-seven (16%) of the patients developed a type of late hematoma: intracerebral hematoma in eight, extracerebral hematoma in six, and postoperative hematoma in 13 patients. Eighteen of the delayed hematomas caused significant mass effect and required surgical evacuation. The hematomas appeared between 2 and 72 hours after admission. In 24 of the 27 patients, a significant increase (> 0.3) in the delta OD occurred prior to an increase in intracranial pressure, a change in the neurological examination, or a change on CT scan. A favorable outcome occurred in 67% of the patients with delayed hematomas, which suggests that early diagnosis using NIRS may allow early treatment and reduce secondary injury caused by delayed hematomas.

Adolescent↗
PubMed1994

Scattering of diffuse photon density waves by spherical inhomogeneities within turbid media: analytic solution and applications.

We present an analytic solution for the scattering of diffuse photon density waves by spherical inhomogeneities within turbid media. The analytic result is compared to experimental measurements. Close agreement between theory and experiment permits the use of the theory to determine the properties of unknown sphere-like objects embedded in turbid media. The analytic solution is extended to encompass several problems of practical interest in imaging, including the influence of multiple sources, multiple objects, and boundaries on the characterization of spherical inhomogeneities. We also extend the solution to encompass time-domain measurements.

Algorithms↗
PubMed1994

Spectroscopic, electrochemical, and ligand binding properties of the horse heart metmyoglobin His64-Tyr variant.

The distal histidine (E7) of horse heart myoglobin (Mb) has been replaced by tyrosine using site-specific mutagenesis. The resulting green Mb variant (His64-Tyr) was expressed in Escherichia coli JM101, isolated and purified to homogeneity. Spectrophotometric pH titrations of the variant exhibit a change in spectrum that occurs with a pKa of 4.7 (25 degrees C). The midpoint reduction potential of the variant is 20 mV (vs. SHE at pH 7, 25 degrees C). Cyanide and azide binding measurements indicate that the oxidized variant binds these anionic ligands with much greater affinity at pH 4.0 than at neutral pH. Extended X-ray absorption fine structure (EXAFS) spectroscopy establishes that the variant is six coordinate at pH 7.0 and pH 4.2. Higher shell contributions to the iron EXAFS observed at pH 7.0 are attributed to tyrosine. These contributions are absent at pH 4.2. Thus, the sixth heme iron ligand of the oxidized variant Mb at pH 7.0 is attributed to oxygen from the hydroxyl group of tyrosine and the sixth ligand present at pH 4.2 is attributed to the oxygen atom of a coordinated water. The EXAFS spectra, electronic absorption spectra, and ligand binding properties of the His64-Tyr Mb variant are consistent with the binding of Tyr-64 as the sixth heme iron ligand between pH 5 and 12 and with the replacement of Tyr-64 by a water molecule at low pH with a pKa of 4.7.

Animals↗
PubMed1994

Bilateral carotid artery occlusion causes periventricular leukomalacia in neonatal dogs.

At 14 days of age, seven mongrel puppies were anesthetized and bilateral carotid arteries, not only the common but also the external and internal carotid arteries, were ligated with sutures. Seven sham-operated littermates served as controls. They were sacrificed at 3 months of age, and their brains were examined macro- and microscopically. Neuropathological examination revealed dilated posterior communicating and basilar arteries in bilateral carotid artery occlusion (BCAO) animals. Six out of 7 BCAO brains had uni- or multiloculated cysts in the periventricular white matter which were surrounded by a band of GFAP-positive glial cells. Scattered small areas of gliosis were found in all experimental animals. Four BCAO brains also showed ventricular dilatation. Although the cerebral cortex seemed to be intact, the periventricular white matter and the corpus callosum were reduced in width in experimental animals. Myelination in the white matter was significantly reduced in BCAO animals compared with the controls. This study directly demonstrates that cerebral hypoperfusion alone can produce periventricular leukomalacia in neonatal dogs.

Animals↗