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L Sokoloff

Publications and source records attributed to L Sokoloff.

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

Lipochondral degeneration of capsular tissue in osteoarthritic hips.

Lipochondral degeneration (LCD) was found in the capsular tissue of 33 of 74 resected osteoarthritic hips studied retrospectively and in 14 of 35 studied prospectively, but never in a control group (n = 46). The process arose in the ligamentous structures that had undergone nodular chondroid metaplasia. The lesion was characterized by vacuolar distention of chondrocytes, eventual necrobiosis, and formation of acellular pools of lipid material. The latter was shown by oil red O staining and electron microscopy. Matrix alterations included glycosaminoglycan depletion, formation of elastin-related material, and degeneration of collagen fibers. There was no significant correlation (p = 0.05) between the occurrence of LCD and the severity of the osteoarthritis; neither was any association found with age, sex, calcium pyrophosphate dihydrate deposition, diabetes mellitus, or coronary artery disease.

Adult↗
PubMed1995

Rates of glucose utilization in brain of active and hibernating ground squirrels.

Rates of glucose utilization (CMRGlc) were determined in some cerebral structures of active warm- and cold-adapted ground squirrels and hibernating ground squirrels with [14C]deoxyglucose (DG) by direct chemical measurement of precursor and products in samples dissected from funnel-frozen brain. The rate of supply relative to demand of glucose and [14C]DG in brain of hibernating animals was similar to or greater than that of controls. [14C]DG cleared from the plasma in hibernators much more slowly than in active animals, and the level of unmetabolized [14C]DG in brain and the integrated specific activity of the precursor pool in plasma exceeded those of the active animals by 4- to 10-fold. At 45 min after an intravenous pulse of [14C]DG, the unmetabolized [14C]DG remaining in the brains of the hibernators accounted for approximately 96% of the total 14C compared with approximately 10-15% in the active animals. The value of lambda, a factor contained in the lumped constant of the operational equation of the [14C]DG method, was estimated for each animal and found to be relatively constant over the sixfold range of glucose levels in the brains of all animals. Calculated CMRGlc in squirrels in deep hibernation was only 1-2% of the values in active animals.

Animals↗
PubMed1995

Determination of local rates of 45Ca influx into rat brain by quantitative autoradiography: studies of aging.

Calcium homeostasis in brain is altered in many conditions, but there is no method to assay quantitatively local calcium flux into brain in vivo. 45Ca uptake into gross-dissected brain regions was measured and compared with results obtained with a quantitative autoradiographic procedure developed to assay influx of 45Ca into brain. Regional calcium contents, brain-to-plasma distribution ratios for calcium and 45Ca, apparent plasma-to-brain transfer coefficients, and net uptake of 45Ca into gross-dissected regions varied by as much as 80%. Local rates of net uptake of 45Ca into 34 structures determined by autoradiography varied by 12- to 14-fold, and rates of movement of 45Ca down concentrations gradients varied by a factor of 7. Previous studies with gross-dissected brain regions suggested changes in calcium uptake into brain during aging, but the values of all the variables assayed in the present study were similar in young adult, middle-aged, and old male rats. A quantitative autoradiographic procedure to assay levels of 45Ca in brain provides the anatomical resolution required to investigate local calcium flux in a variety of physiological and pathological conditions.

Aging↗
PubMed1995

Effects of acute and delayed effects of prior chronic cocaine administration on regional rates of cerebral protein synthesis in rats.

Single or repeated treatments with cocaine (15 mg/kg, i.p.) in rats modify rates of local cerebral protein synthesis (ICPSleu) measured with the [1-14C]leucine method. A single dose of cocaine to naive rats reduced ICPSleu by about 10% throughout the brain; the most statistically significant reduction was in the nucleus accumbens, shell portion (P = .0003). A comparable dose of cocaine administered acutely after 1 wk of daily cocaine injections had no effects on ICPSleu. Delayed effects of prior chronic cocaine treatment were studied in experiments in which one rat of each pair received injections with saline for 8 days and the other cocaine, and on the 15th day ICPSleu was measured. In these experiments delayed effects of the chronic cocaine treatment were observed; in the cocaine-treated rats ICPSleu was significantly increased in selective brain regions, i.e., prefrontal and primary olfactory cortex (P < .006). These results suggest that acute effects of a single dose of cocaine and residual effects of chronic cocaine treatment on ICPSleu are distinctly different and occur in different regions of the brain.

Animals↗
PubMed1994

Local cerebral blood flow during hibernation, a model of natural tolerance to "cerebral ischemia".

The breakdown of cellular homeostasis and progressive neuronal destruction in cerebral ischemia appears to be mediated by a complex network of causes that are intricately interrelated. We have investigated a physiological state existing normally in nature in which mammals appear to tolerate the ordinarily detrimental effects of ischemia with reduced oxygen availability and to resist activation of self-destructive processes, i.e., mammalian hibernation. Ground squirrels (Spermophilus tridecemlineatus) were chronically implanted with arterial and venous catheters and telemetry devices for electroencephalography, electrocardiography, and monitoring of body temperature. The animals were placed in an environmental chamber at an ambient temperature of 5 degrees C. Entrance into hibernation was characterized by a drop in heart rate followed by a gradual decline in body temperature and an isoelectric electroencephalogram. Cold-adapted active animals that were not hibernating served as controls. Cerebral blood flow (CBF) was measured in both groups with the autoradiographic [14C]iodoantipyrine method. Mean (+/- SD) mass-weighted CBF in the brain was 62 +/- 18 ml 100 g(-1) min (-1) (n = 4) in the control group but was reduced to ischemic levels, 7 +/- 4 ml 100 g(-1) min (-1) (n = 4), in the hibernating animals (p < 0.001) [corrected]. No neuropathological changes were found in similarly hibernating animals aroused from hibernation. Hibernation appears to be actively regulated, and hormonal factors may be involved. The identification and characterization of such factors and of the mechanisms used by hibernating species to increase ischemic tolerance and to blunt the destructive effects of ischemia may enable us to prevent or minimize the loss of homeostatic control during and after cerebral ischemia in other species.

Adaptation, Physiological↗
PubMed1994

The use of spectral analysis to determine regional cerebral glucose utilization with positron emission tomography and [18F]fluorodeoxyglucose: theory, implementation, and optimization procedures.

A method for kinetic analysis of dynamic positron emission tomography (PET) data by linear programming that allows identification of the components of a measured PET signal without predefining a compartmental model has recently been proposed by Cunningham and co-workers. The method identifies a small subset of functions from a large input set of feasible functions that best fits the time course of total radioactivity measured by PET. To investigate in detail the properties of this technique, we applied it to PET studies with [18F]fluorodeoxyglucose, a tracer with well-characterized kinetic properties. We examined dynamically acquired data over various time intervals in many brain regions and found that the number of components identified by the method is stable and consistent with the presence of kinetic heterogeneity in every region. We optimized the method for determination of regional rates of glucose utilization; calculated rates were found to be somewhat dependent upon the treatment of noise in the measured tissue data and upon the time interval in which the data were collected. The application of a numerical filter to remove noise in the data resulted in values for regional cerebral glucose utilization that were stable with time and consistent with rates determined by the other established techniques. Based on the results of the current study, we expect that the spectral analysis technique will prove to be a highly flexible tool for kinetic analysis of other tracer compounds; it is capable of producing low-variance, time-stable estimates of physiological parameters when optimized for time interval of application, input spectrum of components, and processing of noise in the data.

Adult↗
PubMed1994

Increases in local cerebral blood flow associated with somatosensory activation are not mediated by NO.

Effects of inhibition of nitric oxide (NO) synthase by NG-nitro-L-arginine methyl ester (L-NAME) on the increases in local cerebral blood flow (LCBF) produced in the whisker-to-barrel sensory pathway by vibrissal stimulation were studied in conscious rats with the autoradiographic iodo[14C]antipyrine method. Unilateral whisker stroking increased LCBF in the ipsilateral trigeminal spinal and principal sensory nuclei, contralateral ventral posteromedial thalamic nucleus, and contralateral somatosensory barrel cortex. Intravenous L-NAME (30 mg/kg) lowered baseline LCBF without altering the percent increases due to stimulation. Intracisternal infusions of L-NAME in doses about 10 times the molar content of free arginine in brain inhibited brain NO synthesis activity by 88%, but the percent augmentations of LCBF by stimulation remained unchanged. Chronic treatment with L-NAME (50 mg/kg ip twice daily for 4 days) inhibited NO synthase activity in brain by 84% but also failed to reduce the percent increases in LCBF due to stimulation. These results indicate that NO does not mediate the increases in LCBF associated with functional activation.

Amino Acid Oxidoreductases↗
PubMed1994

Effects of prolonged sleep deprivation on local rates of cerebral energy metabolism in freely moving rats.

Although sleep deprivation interferes with biological processes essential for performance, health, and longevity, previous studies have failed to reveal any structural or functional changes in brain. We have therefore measured local rates of cerebral glucose utilization (ICMRglc) with the quantitative autoradiographic 2-14C-deoxyglucose method in an effort to determine if and, if so, where sleep deprivation might affect function in sleep-deprived rats. Sleep deprivation was maintained for 11-12 d, long enough to increase whole body energy metabolism, thus confirming that pathophysiological processes that might involve brain functions were evolving. Deep brain temperature was also measured in similarly treated rats and found to be mildly elevated relative to core body temperature. Despite the increased deep brain temperature, systemic hypermetabolism, and sympathetic activation, ICMRglc was not elevated in any of the 60 brain structures examined. Average glucose utilization in the brain as a whole was unchanged in the sleep-deprived rats, but regional decreases were found. The most marked decreases in ICMRglc were in regions of the hypothalamus, thalamus, and limbic system. Mesencephalic and pontine regions were relatively unaffected except for the central gray area. The medulla was entirely normal. The effects of sleep deprivation on brain tended, therefore, to be unidirectional toward decreased energy metabolism, primarily in regions associated with mechanisms of thermoregulation, endocrine regulation, and sleep. Correspondence was found between the hypometabolic brain regions and some aspects of peripheral symptoms.

Animals↗
PubMed1993

Effects of physostigmine on local cerebral glucose utilization in the central components of the rat visual system.

The effects of intravenous administration of physostigmine at doses of 0.03, 0.095, or 0.3 mg/kg on local cerebral glucose utilization (LCGU) were determined in 3 structures of the visual system of the rat brain by means of the quantitative 2-[14C]deoxyglucose method. LCGU was increased in the superior colliculus (superficial gray layer), but unchanged in the visual cortex and the lateral geniculate body. To determine whether the observed effect of physostigmine on the superior colliculus depended on input from the retina, the highest dose of physostigmine was administered to rats which had previously been enucleated bilaterally. Enucleation decreased LCGU in the superior colliculus of the animals not treated with physostigmine and blocked the effect of physostigmine on LCGU. The effect of physostigmine in the superior colliculus appears, therefore, to depend on input from the retina.

Animals↗
PubMed1993

The effects of pharmacologic doses of 2-deoxy-D-glucose on local cerebral blood flow in the awake, unrestrained rat.

Previous studies on the effects of acute insulin-induced hypoglycemia on cerebral blood flow (CBF) have resulted in conflicting results. An alternate approach to the study of glucoprivation is the administration of pharmacologic doses of the glucose analogue, 2-deoxy-D-glucose (2-DG). 2-DG is transported across the blood-brain barrier into brain tissue where it is phosphorylated to 2-deoxy-D-glucose-6-phosphate (2-DG-6-P) but not metabolized further. The 2-DG-6-P accumulates and inhibits the conversion of glucose-6-phosphate to fructose-6-phosphate, thus blocking glycolysis and glucose metabolism. In the present study we have employed the [14C]iodoantipyrine method to examine the effects of a pharmacologic dose (500 mg/kg) of 2-DG on local cerebral blood flow (lCBF) in 29 regions of the brain in conscious, unrestrained, adult male rats. The 2-DG treatment raised arterial plasma glucose levels from 8 to 17 mM without affecting arterial blood pO2, pCO2, or pH but increased lCBF in most brain regions examined. The largest increases were in the cerebral cortex, basal ganglia, and thalamic nuclei (+65 to +157%). Smaller increases were found in most structures of the limbic system, brainstem, and white matter, and no changes in lCBF were seen in the cerebellar cortex and ventral medial hypothalamus. The results indicate that cerebral glucoprivation produced by pharmacological doses of 2-deoxyglucose is accompanied by substantial increase in blood flow in most regions of the brain.

Animals↗
PubMed1993

Proximal femur of Australopithecus africanus from Member 4, Makapansgat, South Africa.

A left proximal femur (MLD 46) from Member 4, Makapansgat, South Africa is described and analyzed. It consists of the head, neck, and a small segment of the shaft that extends to just below the lesser trochanter. The femur exhibits degenerative joint disease in the form of marginal osteophyte formation and thus its taxonomic identity has been somewhat obscured. Consideration of all like-sized mammalian femora from Makapansgat suggests that the femur is that of either a felid or hominid. Comparison of MLD 46 to femora of extent and extinct felids reveals that MLD 46 does not possess two morphological features that are characteristic of felids, namely a deep, prolonged trochanteric fossa and a high neck-shaft angle. Simple shape variables (ratios) and multivariate analyses consistently place MLD 46 with modern and fossil hominids, and most closely align it with the australopithecines. We conclude that the femur is most reasonably attributable to Australopithecus africanus, which is the only hominid yet identified from Makapansgat. Despite its pathological condition, MLD 46 is the most complete proximal femur known for A. africanus, thereby permitting further morphological comparisons with homologues of A. afarensis and Paranthropus. Marginal osteophytes of mammalian femoral heads characteristically occur in individuals of advanced age, suggesting that MLD 46 may have lived some time with the disease. Finally, MLD 46 is considerably larger than the previously described specimen, Sts 14, from Sterkfontein Member 4. There may be as great a contrast in body size in A. africanus as there is between the large and small specimens of A. afarensis.

Animals↗
PubMed1993

Metabolites of 2-deoxy-[14C]glucose in plasma and brain: influence on rate of glucose utilization determined with deoxyglucose method in rat brain.

The [14C]deoxyglucose ([14C]DG) method depends upon quantitative trapping of metabolites in brain at the site of phosphorylation, and in the usual procedure it is assumed that all the label in plasma is in free DG. Our previous finding of labeled nonacidic derivatives of DG in plasma raised the possibility that some metabolites of DG might not be fully retained in body tissues and therefore cause overestimation of the integrated specific activity of the precursor pool determined from assay of label in plasma and/or underestimation of the true size of the metabolite fraction in brain. In the present study, metabolism of DG in rat tissues by secondary pathways was examined and found to be more extensive than previously recognized. When 14C-labeled compounds in ethanol extracts of either plasma or brain were separated by anion exchange HPLC, eight fractions were obtained. 14C-labeled metabolites in plasma were detected after a 35-min lag and gradually increased in amount with time after an intravenous pulse. In brain, deoxyglucose-6-phosphate was further metabolized, mainly to deoxyglucose-1-phosphate and deoxyglucose-1,6-phosphate. These are acid-labile compounds and accounted for approximately 20% of the 14C in the metabolite pool in brain. The rate constants for net loss of 14C from the metabolite pool between 45 and 180 min after a pulse were similar (0.4-0.5%/min) in vivo and in intact postmortem brain. The rate constant for loss of deoxyglucose-6-phosphate (DG-6-P) in vivo (approximately 0.7%/min) was, however, about twice that for postmortem brain, suggesting that a significant fraction of the DG-6-P lost in vivo is due to its further metabolism by energy-dependent reactions. 14C-labeled metabolites of [14C]DG in plasma and brain do not interfere with determination of local rates of glucose utilization in brain in normal, conscious rats by the autoradiographic method if the prescribed procedures and a 45-min experimental period are used.

Animals↗
PubMed1993

Sites and mechanisms of function-related changes in energy metabolism in the nervous system.

Traditional neuroanatomical and electrophysiological methods to localize functional activities in the nervous system focus on perikarya as the sites of activity. Metabolic mapping of local functional activity in the nervous system with the deoxyglucose method has directed interest toward the activity in neuropil. Studies of local glucose utilization (lCMRglc) indicate that energy metabolism is increased by functional activation mainly in terminal projection zones of activated pathways. Electrical stimulation of a pathway raises lCMRglc in the projection zones of the pathway in almost direct proportion to the spike frequency. For example, stimulation of the sciatic nerve produces frequency-dependent metabolic activation in the dorsal horn of the lumbar cord, where the axonal terminals of the afferent pathway reside, with no apparent metabolic effects in the cell bodies of the pathway in the dorsal root ganglia. Functional activation of the hypothalamo-hypophysial pathway by salt-loading increases lCMRglc in the neurohypophysis, the site of the terminal axons of the pathway, but not in the paraventricular and supraoptic nuclei, where the cell bodies of origin of the pathway reside. Activation by hypotension of pathways to these nuclei from brain stem structures involved in baroceptor reflexes does, however, increase lCMRglc in these nuclei. Depolarization induced by electrical stimulation, increased extracellular K+, or opening of Na+ channels with veratridine stimulate lCMRglc in neural tissues, and this increase is blocked by ouabain, a specific inhibitor of Na+,K(+)-ATPase. Activation of this enzyme to restore ionic gradients across cellular membranes appears to trigger the function-related increase in energy metabolism. The metabolic activation is the consequence not of the functional activity itself but of processes operating to recover from that activity.

Animals↗
PubMed1993

Function-related changes in energy metabolism in the nervous system: localization and mechanisms.

Previous neuroanatomical and electrophysiological methods to localize functional activity in the nervous system focus on perikarya as the sites of the activity. Metabolic mapping of local functional activity in the nervous system provides a new dimension, the activity in the neuropil. Studies of local glucose utilization have shown that energy metabolism is increased by functional activation, but the effects are mainly in the terminal projection zones of the activated pathway. Electrical stimulation of a pathway raises glucose utilization in the projection zones of the pathway in almost direct proportion to the spike frequency. For example, electrical stimulation of the sciatic nerve produces frequency-dependent metabolic activation in the dorsal horn of the lumbar cord, where the axonal terminals of the afferent pathway reside, but no apparent metabolic effects in the cell bodies of the pathway in the dorsal root ganglia. Functional activation of the hypothalamo-hypophysial pathway by salt-loading increases glucose utilization in the pituitary neural lobe, where the terminal axons of the pathway reside, but not in the paraventricular and supraoptic nuclei, the sites of the cell bodies of origin of the pathway. Reflex activation by hypotension of pathways to these nuclei from brain stem structures involved in baroreceptor reflexes, however, increases glucose utilization in these nuclei. Depolarization induced by electrical stimulation, extracellular K+, or opening of Na+ channels with veratridine, stimulates glucose utilization in neural tissues, and this increase is blocked by ouabain, a specific inhibitor of Na+, K(+)-ATPase. Activation of this enzyme to restore ionic gradients across cellular membranes appears to trigger the functional activation of energy metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Visually guided reaching with the forelimb contralateral to a "blind" hemisphere: a metabolic mapping study in monkeys.

The 2-14C-deoxyglucose method was used to map local cerebral metabolic activity in monkeys performing a unimanual task requiring visually guided arm reaching and key pressing. The study was carried out with monkeys that either had intact brains or had one hemisphere deprived of visual input by unilateral optic tract section combined in some cases with forebrain commissurotomy. The metabolic mapping revealed activation of sensorimotor cortex only in the hemisphere contralateral to the moving forelimb, irrespective of whether this hemisphere was intact or visually deafferented. These results suggest that visually guided reaching with the forelimb contralateral to the "blind" hemisphere is subserved by that hemisphere's sensorimotor cortex and not by the cortex of the ipsilateral, "seeing" hemisphere. Other areas that were more active metabolically in the "blind" than in the "seeing" hemisphere included the supplementary motor, the secondary somatosensory, and certain posterior parietal cortical areas, intraparietal lateral 5 (lateral 5-ip), 7a, and intraparietal 7 (7-ip). It is suggested that the "blind" hemisphere utilizes at least two distinct pieces of information to guide forelimb movements to visual targets: (1) information about the location of the visual target derived from head and eye movements made to this target and mediated via the inferior parietal cortical areas 7a and 7-ip, and (2) information about the instantaneous upper extremity position derived from forelimb proprioceptive mechanisms and mediated via the somatosensory cortex and thereafter via the superior parietal cortical area, lateral 5-ip.

Animals↗
PubMed1993

Microcracks in the calcified layer of articular cartilage.

Evidence is presented that basophilic radial hairlines in the calcified layer of articular cartilage are in vivo microcracks. They were present in three of 25 normal patellas from subjects below the age of 50 years, in 20 of 25 recently fractured hips (average patient age, 77.3 years), and in 16 of 25 osteoarthritic tibial plateaus (71.7 years). It is hypothesized that extension of these microfractures beyond the calcified layer mediates remodeling of the osteochondral junction in aging and degenerative joint disease.

Adult↗