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Biomedical subjects

L Sokoloff

Publications and source records attributed to L Sokoloff.

At least 127 records · Page 7Linked to original sources
PubMed1987

Local cerebral metabolic effects of L-dopa therapy in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in monkeys.

The quantitative 2-deoxy[14C]glucose autoradiographic method was used to map the distribution of alterations in local cerebral glucose utilization that accompanies clinically effective chronic L-dopa therapy of rhesus monkeys made parkinsonian by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This pattern of changes was compared to the effects of a similar treatment regimen in normal monkeys. L-Dopa (100 mg with 10 mg carbidopa) was administered orally to normal and parkinsonian monkeys 3 times daily for 60-120 days prior to measurement of local cerebral glucose utilization. In parkinsonian monkeys treated with L-dopa, signs and symptoms of parkinsonism were controlled or suppressed, and widespread increases in glucose utilization were seen throughout the brain. Cerebral metabolic activity was increased both in areas rich in dopaminergic receptors, such as the caudate and putamen, and in nondopaminergic areas involved in motor functions. In many structures the rates of glucose utilization in L-dopa-treated parkinsonian monkeys were increased to levels that far exceeded rates measured in normal monkeys. In sharp contrast, similar treatment with L-dopa in normal monkeys had little if any effect on local cerebral glucose utilization. L-Dopa, then, appears to have an action in animals with selective lesions of the substantia nigra pars compacta produced by MPTP that is distinctly different from its effects in the normal monkey.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Effects of insulin on hexose transport across blood-brain barrier in normoglycemia.

The effects of insulin on 3-O-[14C]methylglucose transport across the blood-brain barrier (BBB) were studied in conscious rats under steady-state normoglycemic conditions. The [14C]methylglucose was infused intravenously at a constant rate, and animals were killed at various times between 5 and 30 min after the initiation of the infusion. The time course of the arterial plasma concentration of [14C]methylglucose was determined in timed arterial blood samples taken during the infusion. Local cerebral tissue concentrations of [14C]methylglucose at the time of killing were determined by quantitative autoradiography of brain sections. The rate constants for inward and outward transport of [14C]methylglucose across the BBB, K1, and k2, respectively, were estimated by a least-squares, best-fit of a kinetic equation to the measured time courses of plasma and tissue concentrations. K1 and k2 were reduced by an average of 24 and 31%, respectively, in gray matter and 7 and 16% in white matter from values estimated similarly in normal insulinemic control rats. The equilibrium distribution ratio, K1/k2, for [14C]methylglucose in brain increased by approximately 10-11% in the hyperinsulinemic animals. Because 3-O-[14C]methylglucose shares the same carrier that transports glucose and other hexoses across the BBB, these results suggest that hyperinsulinemia decreases the rate constants for transport but increases the distribution space for hexoses in brain. These effects are, however, quite small and are probably minor or negligible when compared with the major effects of insulin in other tissues.

3-O-Methylglucose↗
PubMed1987

A method for cytologic examination of cartilaginous lesions.

Chondrocytes, dissociated from their matrix with trypsin and clostridial collagenase, retain their cytologic integrity. Successful preparations have been made from postmortem as well as surgical specimens. The method may lend itself to diagnosis of both neoplastic and developmental lesions.

Cartilage↗
PubMed1987

Osteoarthritis as a remodeling process.

Osteoarthritic remodeling involves intimately related events in 3 compartments of the joint surface: the cartilage, osteochondral junction, and capsular tissues. Despite common wisdom, it is difficult to identify abnormalities confined to the cartilage. This places theoretical constraints on what can be accomplished by antiproteases in the treatment of degenerative joint disease.

Adult↗
PubMed1987

Kashin-Beck disease.

Kashin-Beck disease is the most frequent rheumatologic problem of children in China. Although it is acquired environmentally and frequently leads to life-long crippling, the etiology remains an enigma.

Arthritis, Juvenile↗
PubMed1986

Local cerebral glucose utilization in the adult cretinous rat.

Local rates of cerebral glucose utilization were determined in 5-month-old neonatally radiothyroidectomized and control (littermate) rats. Virtually all 48 brain regions examined in the thyroidectomized rats exhibited lower rates of glucose utilization than those of the controls with differences ranging from -24 to -58%. The decreases were particularly large in the cerebral cortex and throughout the auditory system. Altered patterns in the intrastructural distribution of rates of glucose utilization were seen in a number of regions and were particularly prominent in the hippocampus and inferior colliculus. Lesser changes were seen in hypothalamic regions involved in the synthesis of thyrotropin releasing hormone (TRH). The results indicate that the many structural, functional and biochemical abnormalities of cretinism are associated with widespread reductions in energy metabolism throughout the brain.

Animals↗
PubMed1986

The effect of sodium selenite on chondrocytes in monolayer culture.

The effect of sodium selenite on DNA and sulfated proteoglycan synthesis by cultured rabbit articular and growth plate chondrocytes was studied as an in vitro model for Kashin-Beck disease. The selenium content of a defined medium (DMEM, fibroblast growth factor, insulin, and dexamethasone) was below the limit of detection by isotope dilution mass spectrometry. The chondrocytes were viable in the Se-free basal medium. Selenite over a range of 5 X 10(-9) M to 5 X 10(-7) M had no stimulatory effect on DNA or sulfated proteoglycan synthesis by either type of chondrocyte or skin fibroblasts. Proliferation of bovine endothelial cells was enhanced by 5 X 10(-7) M Se. At Se concentrations of greater than or equal to 10(-6) M, there was progressive inhibition of cell growth and radiosulfate incorporation of the connective tissue cells; bovine endothelial cells were more resistant. Twice equimolar concentrations of vitamins C and E exerted no protective effect against the cytotoxicity of higher concentrations of Se. Se supplementation also failed to stimulate growth of human infant chondrocytes. The model enabled simulation of conditions of hyposelenosis below those encountered in nature. The data provide no evidence that chondrocytes have idiosyncratic requirements for Se, and do not support the hypothesis that Se deficiency is a major etiologic factor in Kashin-Beck disease.

Animals↗
PubMed1986

Invalidity of criticisms of the deoxyglucose method based on alleged glucose-6-phosphatase activity in brain.

The observations made by Sacks et al. [Neurochem. Res. 8, 661-685 (1983)] on which they based their criticisms of the deoxyglucose method have been examined and found to have no relationship to the conclusions drawn by them. (1) The observations of Sacks et al. (1983) of constant concentrations of [14C]deoxyglucose and [14C]deoxyglucose-6-phosphate, predominantly in the form of product, reflects only the postmortem phosphorylation of the precursor during the dissection of the brain in their experiments. When the brains are removed by freeze-blowing, the time courses of the [14C]deoxyglucose and [14C]deoxyglucose-6-phosphate concentrations in brain during the 45 min after the intravenous pulse are close to those predicted by the model of the deoxyglucose method. (2) Their observation of a reversal of the cerebral arteriovenous difference from positive to negative for [14C]deoxyglucose and not for [14C]glucose after an intravenous infusion of either tracer is, contrary to their conclusions, not a reflection of glucose-6-phosphatase activity in brain but the consequence of the different proportions of the rate constants for efflux and phosphorylation for these two hexoses in brain and is fully predicted by the model of the deoxyglucose method. (3) It is experimentally demonstrated that there is no significant arteriovenous difference for glucose-6-phosphate in brain, that infusion of [32P]glucose-6-phosphate results in no labeling of brain, and that the blood-brain barrier is impermeable to glucose-6-phosphate. Glucose-6-phosphate cannot, therefore, cross the blood-brain barrier, and the observation by Sacks and co-workers [J. Appl. Physiol. 24, 817-827 (1968); Neurochem. Res. 8, 661-685 (1983)] of a positive cerebral arteriovenous difference for [14C]glucose-6-phosphate and a negative arteriovenous difference for [14C]glucose cannot possibly reflect glucose-6-phosphatase activity in brain as concluded by them. Each of the criticisms raised by Sacks et al. has been demonstrated to be devoid of validity.

Animals↗
PubMed1986

Local cerebral glucose utilization in Long-Evans and Brattleboro rats during acute dehydration.

The quantitative autoradiographic deoxyglucose method was used to study the effects of acute dehydration on local cerebral glucose utilization in Long-Evans and homozygous Brattleboro rats. Water-sated Brattleboro rats had high rates of glucose utilization in the subfornical organ, habenular complex, septal triangular nucleus and pituitary neural lobe. Deprivation of water for 16-18 h enhanced glucose utilization in these structures, more intensely in the Brattleboro rats, and activated others, particularly those connected to the subfornical organ. In Long-Evans rats, water deprivation increased metabolic activity in the subfornical organ, in several structures with which it is connected, and in other brain regions putatively involved in maintaining fluid balance.

Acute Disease↗
PubMed1985

DNA repair by articular chondrocytes. III. Unscheduled DNA synthesis following ultraviolet light irradiation of resting cartilage.

Unscheduled DNA synthesis (UDS) was demonstrated both in fresh slices of rabbit articular cartilage and in resting chondrocytes dissociated from it. Uptake of [3H]thymidine by chondrocytes treated with 10 mM hydroxyurea and irradiated with 254 nm ultraviolet light (20 J/m2) was measured by autoradiography. The UDS in the resting chondrocytes was minuscule compared with that of chondrocytes growing in monolayer culture. It was greater in resting cells from 3- than in 18-month old rabbits but persisted in animals up to 52 months of age. In both resting and cultured chondrocytes, UDS was greatly inhibited by aphidicolin (5 micrograms/ml). The finding of age-related decrease in UDS of resting chondrocytes, contrasted with previously demonstrated lack of it in dividing ones, raises questions about in vitro artefacts in studies of cellular senescence.

Aging↗
PubMed1985

Reexamination of glucose-6-phosphatase activity in the brain in vivo: no evidence for a futile cycle.

Glucose-6-phosphatase activity in the rat brain in vivo was estimated by measuring the differential loss of tritium and carbon-14 from the glucose pool labeled by a mixture of [2-3H]glucose and [U-14C]glucose. The results provide no evidence of significant dephosphorylation of glucose-6-phosphate and do not support the hypothesis of a futile cycle involving glucose-6-phosphatase activity in the brain.

Animals↗
PubMed1985

Effects of lateral habenular lesions on local cerebral glucose utilization in the rat.

The autoradiographic 2-[14C]deoxyglucose method was employed to map the distribution of the changes in local cerebral glucose utilization following unilateral and bilateral electrolytic lesions of the lateral habenula nucleus. Local cerebral glucose utilization was measured one week after the placement of the lesions. Unilateral lesions of the nucleus had no effect on the rates of glucose utilization in the 79 brain structures examined. Bilateral lesions, however, produced selective reductions in glucose utilization in several structures compared to the results in sham-operated animals. Reductions were found in the dorsal and median raphe nuclei and the ventral and dorsal tegmental nuclei which receive projecting fibers mainly from the medial part of the lateral habenula nucleus. The rates of glucose metabolism in the interpeduncular nucleus and mamillary body were also reduced by the bilateral habenular lesions. No anatomic structures rostral to the lesions were metabolically affected.

Animals↗
PubMed1985

Metabolic activation of specific postsynaptic elements in superior cervical ganglion by antidromic stimulation of external carotid nerve.

Using the rat superior cervical ganglion in vivo as a model of the central nervous system, we have sought to determine whether postsynaptic elements as well as terminal processes are metabolically activated during impulse activity. The rate of glucose utilization in the ganglion was found to be stimulated by antidromic stimulation of the external carotid nerve. This stimulation was frequency-dependent and was confined only to the region in the caudal portion of the ganglion corresponding to the location of the cell bodies of origin of the external carotid nerve.

Animals↗
PubMed1985

Alterations of local cerebral glucose utilization during chronic dehydration in rats.

The quantitative autoradiographic deoxyglucose method was used to study changes in local cerebral glucose utilization in conscious dehydrated rats. Animals were either given saline to drink or were deprived of water for 5 days. Saline ingestion did not alter the rates of glucose metabolism in any brain region when compared to the rates of glucose metabolism in animals which had free access to water. Glucose utilization was increased by 140%, however, in the pituitary neural lobe. Water deprivation produced both increases and decreases in glucose metabolism, depending on the particular structure. In 20 of 44 brain structures analyzed, there were significant decreases from -18 to -34% in glucose utilization. Four forebrain structures, the subfornical organ, septal triangular nucleus, and hypothalamic paraventricular and supraoptic nuclei, had increases in glucose utilization of 30-73%. The rate of glucose utilization in the pituitary neural lobe was increased by 367% in water-deprived rats. The results demonstrate that metabolic activity is stimulated in some, but not all, of the structures participating in fluid regulation during an intense thirst challenge. Many brain regions have depressed metabolism in chronic severe dehydration.

Animals↗
PubMed1985

Induction of bone xenografts of rabbit growth plate chondrocytes in the nude mouse.

Subcutaneous transplantation of growth plate chondrocytes isolated enzymatically from the proximal tibia of 6-week-old rabbits into athymic (nu/nu) mice resulted in the formation of cartilaginous nodules. Calcification of the matrix was first seen after 48 hrs, and endochondral ossification at 12 days. The mineral first occurred about hypertrophic cells. Histochemical alkaline phosphatase activity was concentrated in pericellular collars at the same location. Immunofluorescence examination with rabbit anti-mouse lymphocyte serum disclosed that the bulk of the osteoblasts was derived from the mouse. A small quantity of mouse antigen was present in the cartilage matrix at its junction with bone. It presumably diffused into the cartilaginous interface from the host, but the possibility that some chondrocytes were of murine origin has not been excluded. Five of six grafts of cells grown to confluence in monolayer culture for 10 to 14 days became ossified. The ability to induce mineralization declined in subculture. Chondrocytes killed by heating to 56 degrees did not induce calcified cartilage or bone.

Animals↗
PubMed1985

Selective metabolic stimulation of the subfornical organ and pituitary neural lobe by peripheral angiotensin II.

The subfornical organ is a major receptor area for one of the principal stimuli of thirst, the octapeptide, angiotensin II. In conscious water-sated rats, we examined the effects of intravenous infusion of angiotensin II on the rate of glucose utilization in the subfornical organ and in structures anatomically and functionally connected with it. Angiotensin II produced pressor and drinking responses and increased glucose utilization selectively in the subfornical organ and pituitary neural lobe and in no other brain structure. Treatment with the angiotensin II antagonist, sar1-leu8-angiotensin II, before intravenous administration of angiotensin II prevented metabolic stimulation of the subfornical organ and neural lobe. Captopril, an inhibitor of angiotensin-converting enzyme, was administered to homozygous Brattleboro rats, which normally have elevated rates of glucose utilization in the subfornical organ. Captopril reduced subfornical organ glucose metabolism to a level similar to that found in control animals. These results demonstrate that peripheral angiotensin II stimulates glucose metabolism in the subfornical organ under conditions in which it provokes drinking and pressor responses. The findings suggest that circulating angiotensin II is responsible for the high rate of glucose utilization observed in the subfornical organ of Brattleboro rats homozygous for diabetes insipidus.

Angiotensin II↗
PubMed1985

Pathologic features of the femoral head in Mseleni disease.

Severe but atypical osteoarthritic deformities were found in each of 12 femoral heads removed during total hip arthroplasty for Mseleni disease. Although degenerative and regenerative changes were present throughout the cartilage, there was a paucity of eburnation. Histomorphometric analysis of bone at the line of excision indicated that mild osteomalacia was present in four of the 12 specimens. The percentage of the endosteum occupied by osteoid was 9.7 +/- 7.96 (SD) in the patients with Mseleni disease, compared with 5.6 +/- 4.33 in seven African black and 4.1 +/- 2.13 in 13 American white control subjects. The mean thickness of the osteoid seams was not increased. The findings suggest that osteomalacia is not a major pathogenetic factor in Mseleni disease.

Adult↗