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Biomedical subjects

L S Wolfe

Publications and source records attributed to L S Wolfe.

At least 55 records · Page 3Linked to original sources
PubMed1984

Juvenile progressive dystonia: a new phenotype of GM2 gangliosidosis.

A 10-year-old boy developed progressive dystonia and dementia. His symptoms had begun at age 2 1/2 years, and he had been unable to walk by 8 years. At age 10 he was severely dystonic, unable to use his hands to feed himself, and almost anarthric . He had dysphagia and urinary incontinence, and functioned at a 4-year-old level of mental development. The mean percentages of beta-hexosaminidase A measured in serum, leukocytes, and fibroblasts by the heat denaturation method, each on three separate assays, were 5.9, 9.8, and 13.0%, respectively. These values are higher than in Tay-Sachs disease but are similar to levels seen in late-onset or adult cases of GM2 gangliosidosis. This patient appears to represent a new phenotype of juvenile GM2 gangliosidosis having dystonia as the dominant symptom.

Child↗
PubMed1983

Functional disturbances in brain following injury: search for underlying mechanisms.

It was shown previously that local cerebral glucose utilization is less than 50% of normal in all cortical areas of rat brain 3 days following a focal freeze-lesion and that this effect of trauma is significantly diminished by dexamethasone (0.25 mg/Kg/day), and by indomethacin (7.5 mg/Kg single dose). To elucidate the mechanism of action of steroids and non-steroidal antiinflammatory drugs in traumatized brain, the effects of dexamethasone and indomethacin on arachidonic acid release, malondialdehyde production and prostaglandin synthesis in the lesion area were investigated. Five seconds after a freezing lesion arachidonic acid was significantly increased in the lesion area of untreated animals. Neither dexamethasone nor indomethacin had any effect on this release. The thiobarbituric acid reaction, as an estimate of malondialdehyde and non-enzymatic free radical lipoperoxide formation from unsaturated free fatty acids showed no change in the control and lesion areas of untreated and both dexamethasone and indomethacin treated groups. There was a marked increase in PGF2 alpha, PGE2, PGD2 in the lesion area of untreated animals. Indomethacin prevented the formation of prostaglandins by more than 90% while dexamethasone had no effect. These results suggest that some components of the arachidonic acid metabolism must be involved in functional disturbances resulting from trauma while steroid action is mediated in injured brain independently from the prostaglandin cascade.

Animals↗
PubMed1983

Effects of indomethacin and ibuprofen on cerebral metabolism and blood flow in traumatized brain.

Local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) were studied by autoradiographic techniques in indomethacin- and ibuprofen-treated rats with focal cortical freezing lesions. Widespread depression of LCGU, which developed with time after the lesion in untreated animals was significantly diminished by the prostaglandin synthetase inhibitors indomethacin (single injection 7.5 mg/kg) and ibuprofen (36 mg/kg/day). Both drugs were effective when given 6 h before or up to 24 h after the lesion was made. The effect of the drugs was most striking in cortical areas of the traumatized hemisphere, where the depression was most profound in untreated animals. Thus, 3 days after the lesion, average LCGU in these regions was 46%, 86%, and 98% of normal in untreated, indomethacin-pretreated, and ibuprofen-pretreated rats, respectively. Prostaglandin formation was completely inhibited in the lesion area in the indomethacin-treated rats (PGF2 alpha 1.8 ng/g, compared to 57.5 ng/g in untreated and 1.4 ng/g in nonlesioned animals). The results suggest that some components of the prostaglandin system are involved in mechanisms underlying a widespread depression in functional state of the rat brain that develops in response to injury. In control animals, indomethacin was shown to have a biphasic effect on LCBF, an early depression shown previously by others followed at 24 h by a considerable increase.

Animals↗
PubMed1983

High levels of brain dolichols in neuronal ceroid-lipofuscinosis and senescence.

Dolichols as unesterified alcohols were identified as significant components of lipid extracts from storage cytosomes isolated post-mortem from the brains of patients with the infantile, late infantile, and juvenile types of neuronal ceroid-lipofuscinosis (NCL). Very small amounts of dolichols were present in the corresponding subcellular fractions of non-NCL brains. The nuclear fraction from NCL cerebral cortex contained the highest dolichol content expressed per milligram protein or lipid, whereas the crude mitochondrial fraction was the richest in normal brain. Highly significant elevations of dolichol levels were found in human cerebral cortex of patients with NCL and Alzheimer's disease compared with age-matched controls, but the levels were normal in Pick's disease. In human non-NCL cerebral cortex, dolichols increased from 16 micrograms/g at age 5 to over 200 at age 81. Rat cerebral cortex showed a similar progressive increase in dolichol content with age. The high dolichol values in NCL, Alzheimer's disease, and senescence appears to be related to the increase of lipofuscin in brain. This is the first time a uniform biochemical abnormality has been found in all childhood forms of NCL, but the enzyme defect is still unidentified. It may lie on pathways where dolichols and retinyl compounds are recycled in Golgi membranes and derived organelles during the biosynthesis of glycoproteins.

Adolescent↗
PubMed1983

Dolichols in brain and urinary sediment in neuronal ceroid lipofuscinosis.

Long-chain polyisoprenoid alcohols (dolichols) increase more than tenfold from age 5 to 80 years in human cerebral cortex. The dolichol content of brain from infantile, late infantile, and juvenile forms of neuronal ceroid lipofuscinosis (NCL) was significantly higher than in age-matched patients with other neurologic diseases. Significant increase of dolichols was also found in the urinary sediment in all three types of NCL patients, and this test is useful in making the diagnosis. Dolichol accumulation is the first biochemical marker of NCL and seems to parallel storage of ceroid lipofuscin.

Adolescent↗
PubMed1982

Eicosanoids: prostaglandins, thromboxanes, leukotrienes, and other derivatives of carbon-20 unsaturated fatty acids.

In recent years, knowledge of the biochemistry of oxygenated metabolites of arachidonic acid has greatly increased. Their biological functions in acceleration and prevention of platelet aggregation and in inflammatory and immune reactions are becoming much clearer. The therapeutic value, particularly of PGI2 as well as selective inhibitors of synthesis, is also rapidly advancing. Despite much effort, the functional importance of prostaglandins and thromboxanes in the cNS in normal ongoing physiological processes is still quite uncertain. However, when parenchymal or vascular elements are damaged or invaded by extraneural cells, the synthesis of one or the other member of the eicosanoids is greatly increased and contributes significantly to pathophysiological reactions. Thus, prevention of synthesis is likely to have increasing importance in clinical neurology, particularly in cerebrovascular diseases.

Animals↗
PubMed1982

Infantile neuronal ceroid lipofuscinosis: isolation of storage material.

We used ultracentrifugation to isolate autofluorescent storage particles from the brains of patients with infantile type of neuronal ceroid lipofuscinosis (Haltia-Santavuori). The particles differed from those of the late infantile (Jansky-Bielschowsky) and juvenile (Batten-Spielmeyer-Sjögren) types and retained the characteristic appearance--large, partly membrane-bound conglomerates of spherical globules with a uniform finely granular internal structure--despite the vigorous procedure. The sedimentation properties of the particles also differed from the two other forms, but dolichols are found in the particles of all three diseases.

Brain↗
PubMed1981

Biosynthesis of prostacyclin in rat cerebral microvessels and the choroid plexus.

Microvessels, predominantly capillaries, were isolated from rat cerebrum by a modification of published procedures. The morphology and purity of the preparations were monitored by light and electron microscopy and by enrichment in alkaline phosphatase, gamma-glutamyl transpeptidase, and prostacyclin, synthetase. A reversed-phase high-pressure liquid chromatographic method was used in the purification of prostaglandins after extraction from aqueous incubation solutions. Prostacyclin synthesis in brain is localized in cerebral blood vessels and capillaries. The endogenous biosynthetic capacity of the isolated cerebral capillary fractions for prostacyclin, measured as its chemically stable breakdown product, 6-keto-prostaglandin F1 alpha, was 11 ng/mg protein/10 min. Choroid plexus and intact surface vessels synthesized 6-keto-prostaglandin F1 alpha at 37 and 35 ng/mg protein/10 min, respectively. The prostacyclin-synthesizing enzyme of the cerebral capillaries also converted the exogenously added prostaglandin endoperoxides to 6-keto-prostaglandin F1 alpha. Comparison of the synthesis of prostaglandins 6-keto-F1 alpha, E2, and F2 alpha showed that 6-keto-prostaglandin F1 alpha was the major prostaglandin formed in the microvessels, in the larger surface vessels, and in the choroid plexus. Prostaglandin D2 was not detected. Prostacyclin synthesis by the cerebral vasculature is similar to that in other blood vessels and cultured human endothelial cells. Possible physiological roles or prostacyclin in the cerebral microvasculature are discussed with special regard to the autoregulation of cerebral blood flow.

Animals↗
PubMed1979

Origin of the arachidonic acid released post-mortem in rat forebrain.

To determine the origins of the arachidonic acid released post-mortem in brain tissue, [3H]arachidonic acid was injected by the intracerebro-ventricular route and radioactivity monitored in complex lipids and free arachidonic acid at various times after decapitation. The specific activity of the released arachidonic acid was close to that in the total phospholipid fraction and much lower than that of the neutral lipids. The phospholipid with the closest specific activity to the free arachidonic acid recovered at the end of the post-mortem period was phosphatidylinositol. Phosphatidylcholine showed a small but significant decrease in radioactivity post-mortem and could contribute 37% of the arachidonic acid released to the free fatty acid fraction. Arachidonic acid released in rat forebrain after decapitation thus comes from a mixture of phospholipids with phosphatidylinositol and phosphatidylcholine being the major source. Phosphatidylserine and phosphatidic acid did not make important contributions to the free arachidonic acid. In the microsomal fraction, the specific activity of the free arachidonic acid was very close to that in phosphatidylinositol.

Animals↗
PubMed1979

Evidence for the use of a pool of the free arachidonic acid in rat cerebral cortex tissue for prostaglandin F2alpha synthesis in vitro.

To determine if the arachidonic acid which is released post-mortem in rat cerebral cortex is directly available for the in vitro synthesis of prostaglandin F2 alpha, cerebral cortex slices or homogenates were incubated in the presence of [2H8]arachidonic acid. The deuterium to protium ratios in the prostaglandin F2 alpha were compared to those in the free arachidonic acid and other lipids of the tissue after 5 and 60 min of incubation. In the slice, the prostaglandin F2 alpha reached maximum labelling before any of the lipids examined except for a pool of rapidly labelled free arachidonic acid located at the damaged surfaces of the tissue. The prostaglandin F2 alpha recovered in the medium after 60 min of incubation had a deuterium to protium ratio twice that of the prostaglandin F2 alpha found in the tissue. Norepinephrine doubled the labelling of the prostaglandin produced by the slice. The labelling of the prostaglandin F2 alpha in homogenates was 10 times higher than in tissue slices and the deuterium to protium ratio of the total free arachidonic acid was similar to that of prostaglandin F2 alpha. The results indicate that exogenous and endogenous arachidonic acid do not mix appreciably in the intact slice and that the prostaglandin synthetase is present on the damaged surface as well as the intact interior of the slice.

Animals↗