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Biomedical subjects

L Sokoloff

Publications and source records attributed to L Sokoloff.

At least 163 records · Page 9Linked to original sources
PubMed1984

Secondary osteonecrosis in osteoarthritis of the femoral head.

Secondary osteonecrosis was found by pathologic examination in nine (6 per cent) of 150 femoral heads removed surgically for osteoarthritis. The changes were morphologically distinct from the remodeling deformities that supervene late in steroid-induced or idiopathic osteonecrosis. They appeared as infarcts confined to previously eburnated tissue. There were no distinctive clinical or radiologic characteristics. The findings do not lend weight to the hypothesis that unrecognized osteonecrosis is a major etiologic factor in apparently primary osteoarthritis.

Adult↗
PubMed1984

A comparison of local rates of glucose utilization in spinal cord and brain in conscious and nitrous oxide- or pentobarbital-treated rats.

Local rates of glucose utilization in the spinal cord and brain were measured with the 2-[14C]deoxyglucose method in conscious and in paralyzed and mechanically ventilated pentobarbital- or 70% nitrous oxide-treated rats. In conscious animal lumbar spinal cord glucose utilization is only 40-50% that of the cerebral cortex and shows little laminar heterogeneity. Pentobarbital reduces and nitrous oxide increases the cerebral glucose utilization of most structures. The effect of paralysis and nitrous oxide analgesia on lumbar spinal cord glucose utilization is quantitatively similar to that produced in brain; 15-25% increases occur in most spinal cord laminae and cerebral structures. In contrast, the 10-20% reduction in spinal cord gray matter metabolism in the paralyzed and pentobarbital-treated animals is considerably less than the 20-50% depression measured in most brain structures. From these data the authors conclude that, relative to that of most cerebral structures, spinal cord metabolism is less sensitive to depression by barbiturates and suggest that differences in the cell populations of these tissues may account partially for this observation.

Analgesia↗
PubMed1984

2-Deoxyglucose incorporation into rat brain glycogen during measurement of local cerebral glucose utilization by the 2-deoxyglucose method.

The incorporation of 14C into glycogen in rat brain has been measured under the same conditions that exist during the measurement of local cerebral glucose utilization by the autoradiographic 2-[14C]deoxyglucose method. The results demonstrate that approximately 2% of the total 14C in brain 45 min after the pulse of 2-[14C]deoxyglucose is contained in the glycogen portion, and, in fact, incorporated into alpha-1-4 and alpha-1-6 deoxyglucosyl linkages. When the brain is removed by dissection, as is routinely done in the course of the procedure of the 2-[14C]deoxyglucose method to preserve the structure of the brain for autoradiography, the portion of total brain 14C contained in glycogen falls to less than 1%, presumably because of postmortem glycogenolysis which restores much of the label to deoxyglucose-phosphates. In any case, the incorporation of the 14C into glycogen is of no consequence to the validity of the autoradiographic deoxyglucose method, not because of its small magnitude, but because 2-[14C]deoxyglucose is incorporated into glycogen via [14C]deoxyglucose-6-phosphate, and the label in glycogen represents, therefore, an additional "trapped" product of deoxyglucose phosphorylation by hexokinase. With the autoradiographic 2-[14C]deoxyglucose method, in which only total 14C concentration in the brain tissue is measured by quantitative autoradiography, it is essential that all the labeled products derived directly or indirectly from [14C]deoxyglucose phosphorylation by hexokinase be retained in the tissue; their chemical identity is of no significance.

Animals↗
PubMed1984

Stimulation of protein synthesis and glucose utilization in the hypoglossal nucleus induced by axotomy.

The metabolic responses of rat hypoglossal nuclei to unilateral section of the 12th cranial nerve have been studied. Changes in the rates of protein synthesis and glucose utilization in the regenerating nucleus were determined with two quantitative autoradiographic techniques, the L-[1-14C]leucine method and the [14C] deoxyglucose method, respectively. The results show that both of these processes increase in the nucleus ipsilateral to the sectioned nerve and are unaffected in the contralateral nucleus as compared with sham-operated animals. The time courses of these metabolic changes have been compared with that of the return of functional innervation of the tongue. An increase in glucose utilization is first detected 24 hr postaxotomy. It is maximal between 1 and 3 days postaxotomy and constitutes an 84% increase over the rate in the contralateral control nucleus. The increase in protein synthesis is of smaller magnitude than that of glucose utilization. It is maximal at 48 hr after axotomy and constitutes a 25% increase over the rate in the contralateral nucleus. The increases in both of these metabolic processes persist even after functional recovery of the tongue at 21 days postaxotomy. Protein synthesis and glucose utilization return to normal levels between 24 and 35 days postaxotomy. Although the time courses of the changes in protein synthesis and glucose utilization are similar, the magnitude of the increase in glucose utilization is too large to be accounted for by the energy requirements of the relatively small increase in protein synthesis and probably reflects other processes as well, including altered function of the soma-dendritic membrane of regenerating neurons.

Animals↗
PubMed1983

Improved resolution of the 2-deoxy-D-glucose technique.

It was attempted to improve the resolution of the 2-deoxyglucose method. Two principle changes in the procedure were introduced: the gluing of the sections on to the object slide at--20 degrees C and the application of the emulsion with the loop technique. With this approach autoradiographs with grain accumulations over single cell bodies could be observed in many brain regions in addition to a diffuse activity over neuropil.

Animals↗
PubMed1983

Elevated glucose utilization in subfornical organ and pituitary neural lobe of the Brattleboro rat.

Homozygous Brattleboro rats have a genetic inability to synthesize vasopressin and therefore manifest the signs and symptoms of diabetes insipidus. Measurement of local cerebral glucose utilization in these rats has revealed increases specifically localized to the subfornical organ and pituitary neural lobe. Vasopressin replacement reverses the increased glucose utilization only in the subfornical organ. The results suggest that vasopressin regulates the rate of glucose metabolism in the subfornical organ.

Animals↗
PubMed1983

Naloxone pretreatment alters the local cerebral metabolic effect of gamma-hydroxybutyrate in rats.

The effect of naloxone on gamma-hydroxybutyrate (GHB)-induced cerebral metabolic depression was studied in rats with the 2-[14C]deoxyglucose method. Naloxone pretreatment statistically significantly antagonized the cerebral metabolic effect of GHB in 10 of 38 structures examined. These results are consistent with previous data showing reversal of the dopaminergic, electroencephalographic, and behavioral effects of GHB by naloxone and suggest that some of the neuropharmacological effects of GHB are mediated by the endogenous opiate system.

Animals↗
PubMed1983

Hypnogenic center theory of sleep: no support from metabolic mapping in monkeys.

By comparing rates of glucose utilization in brains of monkeys in non-REM sleep and two types of awake controls, we attempted to reveal cerebral hypnogenic centers that drive organisms to sleep through increases in their neural activity. Instead we found that metabolic activity is reduced in all the putative hypnogenic centers during sleep as compared to wakefulness. The results thus offer no support for the notion of an active center that either maintains or triggers sleep.

Animals↗
PubMed1983

The effects of intravenous norepinephrine on the local coupling between glucose utilization and blood flow in the rat brain.

Norepinephrine was infused intravenously in two groups of normal, awake rats. In one group local cerebral glucose utilization (LCGU) was measured by the deoxyglucose method (Sokoloff et al. 1977b); in the other group local cerebral blood flow (LCBF) was determined by the iodoantipyrine method (Sakurada et al. 1978). The experiments were performed during a stable state in which the heart rate was reduced between 36% (LCGU experiments) and 27% (LCBF experiments). Norepinephrine infusion reduced LCGU in all 39 structures measured between - 18 and - 37% from control values obtained in a group of normal non-infused rats. The decrease in LCGU was significant (P less than 0.05) in 38 of the 39 structures tested. LCBF was increased but not statistically significantly in most of the structures examined. When the LCGU values of the various structures during norepinephrine infusion were correlated with their corresponding LCBF values, a tight correlation (r = 0.94) was found indicating a close coupling between LCGU and LCBF during norepinephrine infusion. When compared to the relationship between LCGU and LCBF in a normal, non-infused control group, the slope of the regression line was increased significantly (P less than 0.01) by the norepinephrine infusion, indicating a resetting of the coupling mechanism. This means that, at a given metabolic rate, a higher blood flow is needed to perfuse a brain structure during norepinephrine infusion than during control conditions.

Animals↗
PubMed1983

Xenografts of articular chondrocytes in the nude mouse.

Subcutaneous transplantation of articular chondrocytes isolated enzymatically from immature rabbits and dogs into athymic (nu/nu) mice resulted in the formation of hyaline cartilaginous nodules. Graft rejection was seen when the cells were injected into heterozygous (nu/+) mice. Radiosulfate-labeled proteoglycan extracted from the xenografts had a high buoyant density and was digested by chondroitinase ABC. A monomeric preparation of proteoglycan (A1-D1) contained a small quantity of aggregate as assessed by gel chromatography and gel electrophoresis. Almost no incorporation of 3H-thymidine was found by autoradiography. The matrix did not become calcified over the course of 42 days. The nude mouse system lends itself to testing a variety of problems in the biology of cartilage. These include the redifferentiation of chondrocytes following dedifferentiation in vitro. Species differences were found in this regard. The nodules formed by rabbit articular chondrocytes, grown in monolayer culture for up to 14 days, had a hyaline chondroid character. Dog chondrocytes that had "dedifferentiated" during 14 days of culture prior to transplantation, formed a graft that had a sparse fibrous rather than hyaline matrix.

Animals↗
PubMed1983

DNA repair by articular chondrocytes. I. Unscheduled DNA synthesis following ultraviolet irradiation in monolayer culture.

The hypothesis that aging of articular chondrocytes at a cellular level results from loss of DNA repair capability was studied by measuring unscheduled DNA synthesis (UDS). Cultured rabbit and human articular chondrocytes were irradiated with 254 nm ultraviolet light (20 J/m2) following treatment with 10 mM hydroxyurea. Neither the "in vitro senescence" nor spontaneous transformation that developed during serial passage of rabbit chondrocytes was accompanied by diminution of UDS. Synthesis of sulfated glycosaminoglycans declined more rapidly than the ability of the cells to divide. Levels of UDS by chondrocytes from old donors, rabbit or human, were comparable to those of younger individuals. UDS was greater in human than rabbit chondrocytes. Similar data have been reported previously for dermal fibroblasts but do not necessarily indicate that there is a direct or causative relationship between UDS capability and the longevity of mammalian species. X-Irradiation of rabbit chondrocytes or cartilage explants, in doses up to 40 000 rads, yielded no measurable UDS.

Adult↗
PubMed1983

DNA repair by articular chondrocytes. II. Direct measurements of repair of ultraviolet and X-ray damage in monolayer cultures.

The abilities of human and rabbit articular chondrocytes to repair ultraviolet (UV) and X-ray damage were measured in terms of the removal of UV--endonuclease-sensitive sites (pyrimidine dimers) and single-strand breaks, respectively. The initial 3-h rate of dimer repair in human cells, incubated in medium containing 10% human serum, was about 2.5 times as large as in rabbit cells incubated in medium containing 10% or 20% fetal bovine serum. Similar results have been previously reported for unscheduled DNA synthesis (UDS), indicating that UDS is a valid quantitative measure of repair in this cell system. The repair of single-strand breaks was rapid (approx. 50% completed in less than 10 min). An estimate, from the measured numbers of lesions and patch sizes, indicated that the amount of UDS following 20 krad would be 100 to 300 times less than that in 3 h following 10 J/m2 of 254 nm and hence would not be detectable radioautographically.

Adult↗