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S R Williams

Publications and source records attributed to S R Williams.

At least 73 records · Page 4Linked to original sources
PubMed1997

On the nature of anomalous rectification in thalamocortical neurones of the cat ventrobasal thalamus in vitro.

1. Intracellular sharp electrode current clamp and discontinuous single electrode voltage clamp recordings were made from thalamocortical neurones (n = 57) of the cat ventrobasal thalamus in order to investigate the mechanism underlying anomalous rectification. 2. Under current clamp conditions, voltage-current (V-I) relationships in a potential range of -55 to -110 mV demonstrated anomalous rectification with two components: fast rectification, which controlled the peak of negative voltage deviations, and time-dependent rectification. Time-dependent rectification was apparent as a depolarizing sag generated during the course of negative voltage deviations, was first formed at potentials in the range -60 to -70 mV, and was sensitive to 3 mM Cs+ (n = 6). Similarly, under voltage clamp conditions, instantaneous and steady-state I-V relationships demonstrated anomalous rectification. A slowly activating inward current with an activation threshold in the range of -65 to -70 mV formed time-dependent rectification. This current was sensitive to Cs+ (3 mM) (n = 3) and had properties similar to the slow inward mixed cationic current (Ih). 3. 4-(N-Ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)-pyrimidinium++ + chloride (ZD 7288) (100-300 microM) irreversibly blocked time-dependent rectification mediated by Ih (n = 23 of 25 neurones), and led to a hyperpolarization of the resting membrane potential (6.8 +/- 0.5 mV). In the presence of ZD 7288, V-I and I-V relationships, exhibited fast anomalous rectification, first activated from potential more negative than -80 mV. 4. Ba2+ (100 microM) (n = 8), in the continuous presence of ZD 7288, reversibly linearized peak V-I and instantaneous I-V relationships over a potential range of -70 to -120 mV, and led to a membrane depolarization (13.3 +/- 4.2 mV) or tonic inward current (192 +/- 36 pA). 5. The co-application of ZD 7288 and Ba2+ revealed a depolarizing sag in negative voltage deviations under current clamp conditions, or a large inward current with kinetics two to three times slower than those of Ih under voltage clamp conditions. This novel form of time-dependent rectification was first apparent at potentials more negative than about -85 mV, was sensitive to 5 mM Cs+ (n = 4), and is termed Ih,slow. Ih,slow tail currents reversed between -65.3 and -56.6 mV (with potassium acetate electrodes, n = 3) or -57.6 and -50.3 mV (with KCl electrodes, n = 3). 6. Computer simulations confirmed that the pattern of anomalous rectification in thalamocortical neurones of the cat ventrobasal thalamus is mediated by the concerted action of Ih and a Ba(2+)-sensitive current with properties similar to an inwardly rectifying K+ current (IKIR).

Animals↗
PubMed1997

Pretreatment prediction of the chemotherapeutic response of human glioma cell cultures using nuclear magnetic resonance spectroscopy and artificial neural networks.

Both tumor metabolism and its response to cytotoxic drugs are intrinsic properties of tumor cells. It is therefore likely that there is a relationship between the two properties, however subtle and complex, wherein the metabolic characteristics of tumor cells can reflect the inherent response (resistance or sensitivity) of these cells to cytotoxic drugs. We used artificial neural network analysis to show that it is possible to distinguish, prior to treatment, between drug-resistant and drug-sensitive human glioma cell cultures from their metabolic profiles, as given by high-resolution proton nuclear magnetic resonance spectra of the cell extracts, and to predict their cellular response to the chemotherapeutic drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea in vitro. The results suggest that neural network analysis of tumor nuclear magnetic resonance spectra has potential as a prognostic tool for determining treatment of gliomas, ultimately noninvasively, and may be used to provide information about the metabolic pathways involved in drug response that may be helpful in developing novel treatments for these tumors.

Antineoplastic Agents, Alkylating↗
PubMed1997

Postnatal development of membrane properties and delta oscillations in thalamocortical neurons of the cat dorsal lateral geniculate nucleus.

The development of membrane properties, firing patterns, and delta oscillations in neurons of the cat dorsal lateral geniculate nucleus (dLGN) was investigated in vitro during the first 7 postnatal weeks. Compared with adult neurons, the resting membrane potential was more depolarized at postnatal days 1-9 (P1-P9), the input resistance was higher at P1-P7, and action potentials had a higher threshold and a smaller amplitude at P1-P3 and a longer duration at P1-P9. At P1-P3 trains longer than 200 msec were rarely observed, and trains with more than three action potentials were only present in 41% of the neurons, whereas at P1-P7 the normalized slope of the instantaneous frequencies at the first five interspike intervals was smaller than in the adult. A long-lasting (up to 6 sec) afterhyperpolarization followed a short train of action potentials in 88 and 30% of neurons at P1-P3 and P30-P32, respectively, but it was rarely observed in the adult. The low-threshold Ca2+ potential could evoke a burst of action potentials since P1. However, at P1-P7 the number of action potentials per burst was smaller (range, one to five), and at P1-P9 their maximum instantaneous frequency was lower (<190 Hz) than in the adult (range, six to eight, and 344 Hz, respectively). No delta oscillations were observed until P17, and their frequency (0.36 Hz) was lower than that in the adult (1.8 Hz). The percentage of neurons displaying delta oscillations and their frequency reached adult values by the end of the seventh postnatal week, i.e., well after the maturation of the membrane properties and firing patterns (second postnatal week). In conclusion, the maturation of the electrophysiological properties of thalamocortical neurons in the cat dLGN is completed later than the retinogeniculate axon segregation (Shatz CJ, 1983), and the immaturity of the oscillatory, and not of the burst-firing, activity is a limiting factor in the development of delta waves.

Action Potentials↗
PubMed1997

Silent GABAA synapses during flurazepam withdrawal are region-specific in the hippocampal formation.

Whole-cell patch-clamp recordings were made from CA1 pyramidal and dentate gyrus granule cells (GCs) in hippocampal slices to assess the effects of withdrawal from chronic flurazepam (FRZ) treatment on the function of synaptic GABAA receptors. In slices from control rats, acute perfusion of FRZ (30 microM) increased the monoexponential decay time constant of miniature IPSCs (mIPSCs) in CA1 and GCs (from 3.4 +/- 0.6 to 7.6 +/- 2.1 msec and from 4.2 +/- 0. 6 to 7.1 +/- 1.8 msec, respectively) but did not change their mean conductance, 10-90% rise time, or frequency of occurrence. Withdrawal (2-5 d) from chronic in vivo FRZ treatment (40-110 mg/kg per day, per os) resulted in a dramatic loss of mIPSCs in CA1 neurons. On day 5 of withdrawal, no mIPSCs could be recorded in 40% of CA1 pyramidal cells. In the remaining 60% of the neurons, mIPSCs had a reduced mean conductance (from 0.78 +/- 0.12 nS in vehicle-treated controls to 0.31 +/- 0.05 nS) and a diminished frequency of occurrence (from 20.7 +/- 7.9 to 4.1 +/- 0.6 Hz). We have estimated that >80% of GABAA synapses on CA1 pyramidal cells had become silent, whereas at still-active synapses the number of functional GABAA receptor channels decreased by 60%. This reduction rapidly reverted to control levels on day 6 of withdrawal. FRZ withdrawal did not alter mIPSC properties in GCs. Our results are consistent with the hypothesis that chronic benzodiazepine treatment leads to a reduced number of functional synaptic GABAA receptors in a region-specific manner that may stem from differences in the subunit composition of synaptic GABAA receptors.

Animals↗
PubMed1997

Effects of diffusion anisotropy on lesion delineation in a rat model of cerebral ischemia.

The effects of white and gray matter diffusion anisotropy on ischemic lesion delineation have been studied in the rat model of middle cerebral artery occlusion. Apparent diffusion coefficient (ADC) maps obtained by conventional pulsed gradient spin echo diffusion-weighted imaging (PGSE-DWI) were compared with maps of the trace of the diffusion tensor in both normal and occluded animals. Diffusion tensor trace maps were derived from the average of the ADC maps from three separate experiments with diffusion weighting along three orthogonal axes, and also from a single-scan method. A marked degree of diffusion anisotropy was observed in both cortical gray matter and white matter from ADC maps of the control animals. In the occluded animals, the systematic effects of anisotropy on ADC and lesion area influenced the delineation of the ischemic territory in the PGSE-DWI ADC maps. However, the two trace methods eliminated these effects and gave consistent ischemic lesion depiction, despite the use of differing diffusion times in the two measurements.

Animals↗
PubMed1997

Autoradiographic imaging of cerebral ischaemia using a combination of blood flow and hypoxic markers in an animal model.

Current routine clinical techniques, including angiography and perfusional single-photon emission tomography, can be used to indicate problems in cerebral vascular supply and areas of cerebral hypoperfusion following a stroke, but cannot distinguish between ischaemic core and penumbra. In order to image specifically the penumbra, a method or indicator should be able to define areas with reduced blood flow, and a degree of metabolic compromise. In this context, the tissue could be regarded as hypoxic rather than ischaemic, and we have therefore chosen to investigate the potential of radio-labelled hypoxic markers in the study of ischaemia. In order to combine a hypoxic marker with a blood flow marker we used technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) and iodine-125 iodoazomycin arabinoside (125I-IAZA), during cerebral ischaemia in the rat middle cerebral artery occlusion model. 99mTc-HMPAO and 125I-IAZA were injected simultaneously 2 h following occlusion of the middle cerebral artery, and 5 h before decapitation. Paired autoradiograms were produced and compared. Three distinct patterns emerged from the autoradiograms: slightly decreased perfusion with no uptake of the hypoxic marker indicating an area of misery perfusion; moderately decreased perfusion with concomitant uptake of iodoazomycin arabinoside, a region of hypoxia; and severely decreased perfusion with no retention of the hypoxic tracer. In conclusion, we present a new use for an imaging agent in the investigation of cerebral hypoxia. This agent, IAZA together with HMPAO, provides a means of separating the penumbra into regions of misery perfusion and hypoxia. The potential impact of this may be important in the clinical investigation of stroke.

Animals↗
PubMed1997

Clarithromycin-induced ventricular tachycardia.

Clarithromycin is a relatively new macrolide antibiotic that offers twice-daily dosing. It differs from erythromycin only in the methylation of the hydroxyl group at position 6. Although the side-effect profile of erythromycin is established, including gastroenteritis and interactions with other drugs subject to hepatic mixed-function oxidase metabolism, experience with the newer macrolides is still being recorded. Cardiotoxicity has been demonstrated after both intravenous and oral administration of erythromycin but has never been reported with the newer macrolides. We report a case of ventricular dysrhythmias that occurred after six therapeutic doses of clarithromycin. The dysrhythmias resolved after discontinuation of the drug.

Adult↗
PubMed1997

Successful treatment of crotalid-induced neurotoxicity with a new polyspecific crotalid Fab antivenom.

STUDY OBJECTIVE: To report the effectiveness of a new polyvalent crotalid antivenom on neurotoxicity associated with North American rattlesnake envenomation. Two syndromes of crotalid-induced neurotoxicity have been reported. In severe envenomation by Crotalus scutulatus scutulatus (Mojave rattlesnake), weakness and fasciculations of various muscle groups, including those innervated by cranial nerves, may develop. Occasionally respiratory insufficiency develops. The second neurotoxic effects is myokymia, a type of fasciculation most frequently reported after bites by Crotalus horridus horridus (timber rattlesnake) and Crotalus atrox (Western diamondback rattlesnake). Conventional polyvalent antivenom is often ineffective in the treatment of venom-induced neurotoxicity. METHODS: We report a case series of three patients envenomated by North American rattlesnakes, one of which was identified as C scutulatus scutulatus. All three patients experienced neurotoxicity with weakness, paresthesias, and dramatic fasciculations, along with other signs and symptoms of crotalid venom poisoning. RESULTS: The administration of new polyspecific crotalid antivenom made of ovine Fab was successful in immediately and completely reversing neurotoxicity in each of these patients. CONCLUSION: We report the use of a new antivenom for North American crotalid envenomation that seems to have efficacy in reversing neurotoxicity associated with these bites.

Adult↗
PubMed1997

Association of rattlesnake bite location with severity of clinical manifestations.

STUDY OBJECTIVE: To examine an association between bite location in cases of North American crotalid envenomation and the severity of clinical manifestations. METHODS: We conducted a retrospective review of prospectively collected data for an experimental trial of crotalid antivenom. Our subjects were otherwise healthy individuals with minimal to moderate North American crotalid envenomation. We compared the severity of envenomation for patients with digit bites distal to the proximal interphalangeal joint and bites more proximal using a previously developed and validated snakebite severity score. RESULTS: Thirteen subjects were classified as having distal bites and 24 as having proximal bites. At baseline (before antivenom administration), the distal group had a mean severity score of 2.9 +/- 1.1, whereas the proximal group had a mean severity score of 5.0 +/- 2.2 (P = .0024). Patients in the proximal group tended to demonstrate a more rapid initial decline in severity score after receiving antivenom than did the distal group. CONCLUSION: In minimal to moderate North America crotalid envenomation, patients who sustained bites on distal aspects the digits tended to experience less severe clinical manifestations of envenomation. It is possible that an isolated bite to the distal aspect of a finger is an early marker of minimal envenomation.

Adolescent↗
PubMed1997

Metabolic studies of human primitive neuroectodermal tumour cells by proton nuclear magnetic resonance spectroscopy.

Well-characterized cell lines established from primitive neuroectodermal tumours (PNETs) were examined by proton nuclear magnetic resonance (1H-NMR) spectroscopy and chromatographic analysis of perchloric acid extracts, following amplification in cell culture. A characteristic 1H-NMR spectroscopic metabolite pattern was found for medulloblastoma cell lines, which clearly discriminates these cells from PNETs of other locations in the central nervous system (CNS), on the basis of their N-acetyl aspartate (NAA) and aspartate expression. Medulloblastoma cell lines were heterogeneous in respect of their metabolite expression, possibly owing to the heterogeneity in their differentiation along lineages of the CNS. All PNET spectra displayed similar features, including decreased NAA and creatine peaks and increased signals from choline compounds (Cho) compared with normal cerebellum. The expression of NAA by the medulloblastoma lines was in the opposite order to the extent of neuronal differentiation, which may indicate their origin from a progenitor cell with the phenotype of an oligodendrocyte-type-2 astrocyte cell.

Aspartic Acid↗
PubMed1997

Body habitus and coronary heart disease in men. A review with reference to methods of body habitus assessment.

Table 1 is a synopsis of the major findings from an extensive literature on the association between human body habitus and coronary heart disease. Whilst some studies have used quite sophisticated laboratory procedures to quantify body fat most have relied upon anthropometric measurements to determine some component of body habitus. Of these, body weight and height are the simplest measurements and are, therefore, well-suited to large-scale prospective studies. Height and weight are highly reproducible measurements, although in the short term, weight can have considerable physiological variation associated with gastric emptying and state of hydration. Less reliable measurements than height and weight are skinfolds and body circumferences, both of which have been used extensively in cross-sectional and prospective analyses. For skinfolds, both the inter and intra-observer variability is affected by the measurement technique, location of the skinfold site, the skinfold caliper used and skinfold compressibility. As measurement error has been shown to be a function of skinfold thickness, accurate and repeatable skinfold measurements are particularly difficult to make in the obese. In these subjects, it is not always possible to locate a specific anatomical bony landmark or to pull a parallel skinfold away from the underlying tissue. Furthermore, in the extremely obese it is sometimes possible for a skinfold to be thicker than the jaws of the currently available commercial calipers. Alternately, body circumferences are obtainable in all subjects and have greater reproducibility than skinfolds. They are, therefore, the preferred method in obese subjects. However, there is considerable work to be done to establish their association with body fatness. The evidence examined in this review suggests that body weight is a poor predictor of coronary heart disease. Some studies have reported no difference in the body weight of coronary heart disease patients compared to subjects free of the disease, others found the body weight of subjects with coronary heart disease to be slightly greater, and one found the body weight of cardiac patients to be less than controls. Height, however, is associated with coronary heart disease in prospective studies with long-term and shorter-term follow-up periods and case-control designs. Fetal, infant and childhood under-nutrition may link shorter adult height and susceptibility to cardiovascular disease. Many researchers have studied the relationship between overweight and coronary heart disease by using a surrogate measurement of body fatness such as relative weight or a weight-for-height index. In general, results produced by these studies suggest weight-for-height indices, particularly the often used body mass index, are not strong predictors of coronary heart disease. Indeed case-control designs have consistently failed to show a relationship between body mass index and coronary heart disease. Inconsistent results from prospective studies, however, are difficult to interpret. To further confuse the situation, the body mass index has been examined in relation to different coronary heart disease end-points and adjusted for different confounding variables. Explaining the inconsistent results on the basis of length of follow-up is also not straightforward. When follow-up periods exceed 20 years, and sample size is small, however, this closer association has not been found, even with a long follow-up period. Whilst some studies have found no association after 15, 13 and 12 years others have reported a relationship after 8.5, 10, 12, 10 and 7 years. The 22 year follow-up evidence from the Framingham Study shows the strongest 'independent' association between body mass index and coronary heart disease. (ABSTRACT TRUNCATED)

Adult↗
PubMed1997

Acute bilineage leukemia after chronic myelogenous leukemia.

Blastic transformation of chronic myelogenous leukemia may involve any hematopoietic lineage, including that of lymphocytes. In a minority of cases, the blasts express characteristics of both myeloid and lymphoid cells (biphenotypic) or comprise two separate populations of myeloid and lymphoid cells (bilineage leukemia). In a coordinated effort, we used a sequence of morphologic, cytochemical, immunocytochemical, and molecular biological studies to identify a case of bilineage blastic transformation of CML with a predominance of lymphoid blasts. The patient was treated for ALL and responded. The case presented illustrates the need for greater flexibility by the physician and laboratory to determine the specific diagnostic requirements for patients with hematologic malignancy with unusual phenotypic characteristics.

Aged↗
PubMed1996

Immortalization and transformation are associated with specific alterations in choline metabolism.

Analysis of transformed, immortalized, and primary rat Schwann cells by high-resolution proton nuclear magnetic resonance spectroscopy reveals that immortalization of Schwann cells (by SV40 large T antigen) induced a decrease in sn-glycero-3-phosphocholine (GPCho), whereas H-ras alone, which is known to cause growth arrest in these cells, induced a marked increase in GPCho and a decrease in phosphocholine (PCho). An increase of PCho was found only in cells fully transformed by both oncogenes together. Moreover, we examined 11 human tumor cell lines, all of which expressed a PCho:GPCho ratio similar to that of fully transformed rat Schwann cells. Importantly, neither the absolute levels of PCho nor the ratio of PCho:GPCho were correlated with the rate of cell division across a range of normal (primary cultures) and transformed cells. Thus, raised PCho:GPCho ratios may serve as an indicator of multiple oncogenic lesions and malignancy in noninvasive tumor investigations.

Animals↗
PubMed1996

Electrophysiological and morphological properties of interneurones in the rat dorsal lateral geniculate nucleus in vitro.

1. Intracellular recordings were made from putative interneurones (n = 24) and thalamocortical (TC) projection neurones (n = 45) in slice preparations of the rat dorsal lateral geniculate nucleus (dLGN) in order to compare the electrophysiological properties of these neuronal types. 2. Intracellular injection of biocytin to electrophysiologically identified neurones (n = 34) revealed the morphology of putative interneurones (n = 4) to be similar to class B and that of TC neurones (n = 30) to be similar to class A Golgi-impregnated neurones. 3. Interneurones had resting membrane potentials (-52 mV) relatively positive to those of TC neurones (-63 mV), shorter time constants (36.8 and 58.2 ms, respectively), but similar steady-state input resistances (164 and 180 M omega, respectively). Steady-state voltage-current relationships were nearly linear in interneurones, but highly non-linear in TC neurones. 4. The structure of action potential firing evoked at the break of hyperpolarizing voltage transients was dependent upon neuronal type. Interneurones fired a single action potential or a burst of action potentials with a maximum frequency of < 130 Hz, whilst TC neurones fired a high frequency burst with a minimum frequency of > 250 Hz. In addition, well-defined burst firing of action potentials in response to depolarizing voltage excursions, from membrane potentials negative to -65 mV, could be evoked in TC neurones, but not in interneurones. 5. The directly evoked action potentials of interneurones were characterized by an initial slow pre-potential preceding the fast upstroke of the action potential. The amplitude and width of interneurones' action potentials were smaller than those of TC neurones and the amplitude and duration of the single action potential after-hyperpolarization were greater in interneurones. Both interneurones and TC neurones fired action potentials repetitively in response to suprathreshold voltage excursions, with interneurones demonstrating a greater degree of spike-frequency adaptation. Following a train of action potentials, interneurones and TC neurones generated a slow after-hyperpolarizing potential: in interneurones but not TC neurones this potential was followed by a slow depolarizing potential. 6. An intrinsic, subthreshold membrane potential oscillatory activity with a mean frequency of approximately 8 Hz was observed in interneurones. 7. Electrical stimulation of the optic tract evoked in interneurones apparently pure EPSPs, pure IPSPs or a mixture of EPSPs and IPSPs. EPSPs were found to be biphasic and mediated by the activation of non-N-methyl-D-aspartate (NMDA) and NMDA excitatory amino acid receptors. IPSPs and the response to the iontophoretic application of GABA were found to reverse between -65 and -70 mV. The application of GABAB receptor agonists failed to affect the membrane properties of six of seven interneurones tested. In addition spontaneous EPSPs and IPSPs were recorded in interneurones. 8. These results demonstrate that the electrophysiological properties of putative interneurones are distinct from those of TC neurones of the rat dLGN. The implications of these findings for the control of visual responsiveness of TC neurones are discussed.

Animals↗
PubMed1996

A model for quantification of perfusion in pulsed labelling techniques.

A model for quantification of perfusion in pulsed labelling techniques is described, based on solving the modified Bloch equation including the effects of flow. The model is designed to fit experimental data acquired in two separate measurements (inversion and control, or selective and non-selective inversions) for different inversion times using a biexponential. Although the signal contrast is 50% less than the continuous labelling technique, it seems more appropriate for human studies because of its lower power deposition, shorter transit time and the use of an interleaved acquisition. The importance is shown of including in the model the difference in relaxation time between blood and tissue. Neglecting this difference can lead to an overestimation of flow, which can be as big as 100% in white matter and 20% in grey matter.

Cerebrovascular Circulation↗
PubMed1996

Metabolic effects of cold storage on livers from euthermic and hibernating Columbian ground squirrels.

The current study was undertaken to investigate energy metabolism during hypoxia in the cold in livers from euthermic and hibernating Columbian ground squirrels. We hypothesized that the hibernating Columbian ground squirrel would be able to maintain liver energetics for a considerably longer time than euthermic animals. Particular reference was made to the function of glycolysis, which is the only mechanism for energy production under hypothermic ischemia. The transition from aerobic to anaerobic metabolism was apparent in both euthermic and hibernating animals as lactate levels rose within 1-3 h; total lactate accumulation was 2.5 micromol/g in both groups. In euthermic squirrels, liver ATP and ADP decreased considerably over the first 3-h storage; values dropped by 55% and 34%, respectively. Conversely, as the drain on high energy phosphate pools progressed, there was an increase in low energy adenylate, AMP. Between 10 and 24 h of storage, increases in AMP accounted for approximately 25-30% of total ATP + ADP decrease. The remainder of the drop in adenylates was accounted for by considerable decreases in total adenylate (TA) contents; by 24 h TA contents had decreased by 2.0 micromol/g. Livers from hibernating squirrels exhibited similar patterns of adenylate change and were not significantly higher than their euthermic counterparts. With respect to regulatory control of glycolysis, livers from euthermic squirrels exhibited no regulatory control at phosphofructokinase (PFK) or pyruvate kinase (PK). Livers from hibernating animals, however, showed an activation at PFK by 10 h of cold storage; levels of hexose phosphates, glucose-6-phosphate + fructose 6-phosphate (G6P + F6P), dropped and fructose 1, 6-biphosphate (F1,6P2), increased. Changes in metabolite levels (phosphoenolpyruvate and pyruvate) associated with another key suspect regulatory enzyme, PK, indicated no role in regulatory control of glycolysis during the 24-h period. The apparent increase in PFK responsiveness to declining energy stores may be a futile activation since there was no accompanying increase in anaerobic end product, lactate, and no maintenance of energetics.

Adenine Nucleotides↗
PubMed1996

Proton nuclear magnetic resonance spectroscopy of lactate production in isolated rat liver during cold preservation.

Lactate-edited 1H NMR difference spectra have been acquired from intact rat liver tissue following flushing and preservation in ice. A peak, initially at 1.26 ppm, was seen to increase in the liver tissue with preservation time. This peak was assigned to lactate, despite the fact that its chemical shift was initially shifted by approximately -0.1 ppm relative to an externally added standard. The assignment was based on the following: (a) the peak increased over a 24-h ischemic storage period; (b) it was coupled to a signal 2.78 +/- 0.02 ppm upfield; and (c) a parallel increase in lactate was noted in perchloric acid extracts of tissue from the same liver. An additional peak, assigned to alanine, was also observed during storage and was also shifted by approximately -0.1 ppm. Inclusion of dimethyl sulfoxide, which readily permeates liver tissue, demonstrated that this chemical shift alteration was a tissue-specific effect. These results demonstrate that 1H NMR spectroscopy of intact liver tissue during hypothermic ischemia is possible, though chemical shift assignments should be made with caution.

Animals↗