bluuebunny/crossref_metadata_2025_split huggingface dataset:
NEUROCHEMISTRY OF THE MUCOPOLYSACCHARIDOSES: BRAIN GLYCOSAMINOGLYCANS, LIPIDS AND LYSOSOMAL ENZYMES IN MUCOPOLYSACCHARIDOSIS TYPE III B (α‐N‐ACETYLGLUCOSAMINIDASE DEFICIENCY)
Authors: Constantopoulos George , Eiben Robert M. , Schafer Irwin A. 
Published: October 2006

AbstractGlycosaminoglycans, lipids and lysosomal enzymes were measured in brain, liver and spleen of a patient with mucopolysaccharidosis Type III B (α‐N‐Acetylglucosaminidase deficiency).The glycosaminoglycan content of the brain gray and white matter, leptomeninges, spleen and liver of the patient was 4, 3, 10, and 100 times greater than that of the respective tissues of normal controls. Partially degraded heparan sulfate, the concentration of which increased 17 times in the brain, accounted for the increased glycosaminoglycan content of all tissues.The concentration of the gangliosides GM2, GM3 and GD3 was markedly increased in the gray matter, and to a smaller degree in the white matter. Ceramide dihexoside was also increased in the gray matter of the patient with MPS III B.The activity of α‐N‐Acetylglucosaminidase was absent from the brain and the liver and greatly diminished in the spleen. β‐Glucuronidase. β‐glucosaminidase and α‐l‐iduronidase were more active than normally and the activity of α‐galactosidase and β‐galactosidase was markedly reduced.
BIOCHEMICAL EFFECTS IN MAN and RAT OF THREE DRUGS WHICH CAN INCREASE BRAIN GABA CONTENT
Authors: Perry Thomas L. , Hansen Shirley 
Published: October 2006

Abstract— Brain amino acids were measured in rats given aminooxyacetic acid (AOAA) by mouth, and in rats given sodium dipropylacetate (DPA) both orally and by intraperitoneal injection. Brain GABA content was significantly elevated by AOAA doses of 10mg/kg/day, but not by 5mg/kg/day. Approximately 4 times as much AOAA is required by mouth as by parenteral injection to raise brain GABA content in the rat. DPA (400mg/kg) increased brain GABA and lowered brain aspartate content significantly 1 h after a single injection. However, DPA given orally (350 mg/kg/day) produced no alterations of any amino acids in rat brain.Amino acids were measured in plasma and urine from patients treated orally with isonicotinic acid hydrazide (INH) or DPA, and from a volunteer who took AOAA. INH (10–21 mg/kg/day) increased concentrations of β‐alanine and ornithine in plasma, as well as urinary excretion of β‐alanine. DPA had no such effect. AOAA in oral doses ranging from 1.25 to 5.0 mg/kg/day increased plasma concentrations of β‐alanine, ornithine, β‐aminoisobutyric acid, proline and hydroxyproline, and produced massive urinary excretion of β‐alanine, β‐aminoisobutyric acid, and taurine.Both INH and AOAA, given in doses practical for human use, inhibit the transamination of β‐alanine and ornithine in liver, and may also inhibit the transamination of GABA in brain. In addition, AOAA interferes with the catabolism of β‐aminoisobutyric acid, proline, and hydroxyproline. AOAA, in the lowest dose employed, appeared more effective than INH as an inhibitor of GABA aminotransferase in man, and might therefore be useful in the treatment of neurological diseases in which brain GABA is deficient.
CHARACTERIZATION OF A RAT BRAIN FUCOSYL‐TRANSFERASE
Authors: Broquet P. , Perez‐Gonzalez M. N. , Louisot P. 
Published: October 2006

Abstract—Rat brain fucosyl‐transferase was solubilized using Triton X–100 detergent, and then purified by electrofocusing.From studies of some exogenous glycoproteinic acceptors, desialylated fetuin appeared to be the most effective substrate. Study of initial velocity patterns gave evidence for a BiBi sequential mechanism, assumed to be a random BiBi with dead end inhibition.
A CALCIUM ACTIVATED PROTEASE IN SQUID AXOPLASM
Authors: PANT Harish C. , Terakawa Susumu , Gainer Harold 
Published: October 2006

AbstractEvidence for a protease in squid axoplasm which is selectively activated by Ca2+ and blocked by SH‐inhibitors is presented. This protease appears to be particularly effective in degrading squid neurofilament proteins, but also extensively degrades various other major protein components in axoplasm.
ACID AND ALKALINE PHOSPHATASES IN A BRAIN TUBULIN PREPARATION
Authors: Larsson H. , Wallin Margareta , Edström A. 
Published: October 2006

AbstractThe hydrolysis of p‐Nitrophenylphosphate has been studied in vitro in a tubulin preparation from bovine brain. The activity at pH 6.8 was 16.4 ± 2.2 nmol/mg protein, h.At least two phosphatases were responsible for this activity. They were found to have pH‐optima at 5.1 and 10.4. respectively, and their apparent KM values were 1.23 ± 0.10 mm and 0.17 ± 0.03 mm. respectively. Mg2+ was found to stimulate activity at both pHs while Zn2+ inhibited at pH 5.1 and stimulated activity at pH 10.4.All of the alkaline and part of the acid phosphatase activity were found to be closely associated with microtubules/tubulin. Tubulin purified by phosphocellulose chromatography contained phosphatase activity, and it is suggested that such activity is an intrinsic property of tubulin itself.Phosphatase activity was also found in association with the microtubule‐associated proteins that co‐purify with tubulin. Two proteins of high molecular weight constituted the major part of the associated material. The results indicate an association of phosphatase activity with the larger of these two proteins.
CALCIUM‐DEPENDENT ALTERATIONS OF NEUROFILAMENT PROTEINS OF RAT PERIPHERAL NERVE
Authors: Schlaepfer William W. , Micro Steven 
Published: October 2006

AbstractSegments of rat peripheral nerve were excised and incubated in vitro under conditions which hasten or retard the penetration of calcium into tissues. The nerve segments were then homogenized in 1%SDS, 8 M‐urea and 50mM‐dithioerythritol and the extracted proteins were analyzed by SDS polyacrylamide disc gel electrophoresis. Representative samples were also fixed and processed for electron microscopic examinations.Incubational conditions which favored the penetration of calcium into the tissues caused widespread granular disruption of neurofilaments as well as the selective loss of 200,000, 150,000 and 69,000 MW proteins from the nerve segments. These structural and chemical changes occurred in the 24‐48 h interval during incubation at 37oC under nutrient conditions, but were accelerated under energy‐deprived conditions and with high‐calcium media. The same changes occurred in nerve segments incubated for 2h in media containing calcium with Triton X‐100 detergent or A23187 ionophore and in nerve segments freeze‐thawed in 0.5 mM‐calcium. These changes did not occur after parallel incubations in calcium‐free media. These findings support the view that 200,000, 150,000 and 69,000 MW proteins are components of neurofilaments and that they are susceptible to a calcium‐induced disruption.
GANGLIOSIDE1−COMPOSITION OF BRAIN IN TAY‐SACHS DISEASE: INCREASED AMOUNTS OF GD2 AND N‐ACETYL‐β‐D‐GALACTOSAMINYL GD1a GANGLIOSIDE
Authors: Iwamori M. , Nagai Y. 
Published: October 2006

Abstract— The ganglioside composition of the brain of a patient with Tay‐Sachs disease (TS‐brain) was determined by a newly developed ganglioside‐mapping procedure and compared with that of an age‐matched control brain. GM2 ganglioside was the predominant component in TS‐brain and the following gangliosides were also found, GM1, GD1a, GD1b and GT1 (major gangliosides in normal brain), and GM3, GD3, GD2 and GD1a‐GAN (minor or undetectable components of normal brain). Individual gangliosides were isolated by column chromatography using a combination of DEAE‐Sepharose, Iatrobeads and Silica Gel 60 and their structures were confirmed by comparing them with authentic standards using TLC, analysing their carbohydrate compositions by gas‐liquid chromatography and cleaving them sequentially with glycosidases. The amounts of individual components were measured by quantitative densitometric scanning of the thin‐layer plates. As a reflection of myelin breakdown, no sialosylgalactosyl ceramide was detectable in TS‐brain. Although the total amounts of all gangliosides except GM2 in TS‐brain were low, there were normal molar ratios of the main gangliosides in normal brain, that is, GM1, GD1a, GD1b and GT1. In comparison with the amount of GDla ganglioside, the amounts of GM2, GD2 and GD1a‐GAN, which contain N‐acetylgalactosamine as a terminal carbohydrate residue, were all elevated in TS‐brain. The long chain bases of individual gangliosides contained both C‐18 and C‐20 sphingosine in different ratios and the ratio of C‐20 to C‐18 increased in the gangliosides in the order: GM2 < GM1 < GD1a < GD1a‐GAN < GD1b < GT1 in both normal brain and TS‐brain. In contrast, GD2 and GD3 gangliosides consisted mainly of C‐18 sphingosine. The C‐20 to C‐18 ratios of individual gangliosides in the TS‐brain were lower than those of age‐matched control brain.Hexosaminidase from Turbo cornutus showed the same specific activity and Km value in catalysing the cleavage of terminal N‐acetylgalactosaminyl residues from GM2, GD2 and GD1a‐GAN, suggesting that the brain gangliosides that increase in Tay‐Sachs disease may be cleaved by the same enzyme.
Correlations Between Acetylcholinesterase Activity in Guinea‐Pig Iris and Pupillary Function: A Biochemical and Pupillographic Study
Authors: Søli N. E. , Karlsen R. Lund , Opsahl M. , Fonnum F. 
Published: October 2006

Abstract: Acetylcholinesterase (AChE) in guinea pig iris was inhibited by methylisocyclopentylfluorophosphate (soman) administered topically or parenterally, and enzyme activity was correlated to pupillary diameter by infrared pupillography. After a single topical soman instillation into the conjunctival sac there was an almost linear relationship between the reduction in AChE activity and pupillary diameter. Topical administration of soman at 24‐h intervals in doses capable of almost complete inhibition of AChE in iris was accompanied by a reduced miotic effect of this drug. This was indicated by a reduced rate of the soman‐induced pupillary constriction, a less pronounced reduction in pupillary diameter, and a more rapid return of the pupillary diameter to normal size. The change in pupillary diameter occurred after three daily administrations and remained constant during 31 days of treatment. These observations were seen irrespective of inhibition of blood AChE. The decrease in response to repeated administration could not be explained by a reduced inhibitory effect of soman on AChE, by a more rapid de novo synthesis of AChE, or by a change in the number of the muscarinic receptors as determined by quinuclidinyl benzilate binding. When soman or DFP was administered subcutaneously in high doses a severe AChE inhibition was obtained in iris without any concomitant miosis.
Physical and Kinetic Properties of Choline Acetyl Transferase from Rat and Bovine Brain
Authors: Ryan Rick , McClure William O. 
Published: October 2006

Abstract:Several physical and kinetic properties of highly purified choline acetyltransferase (EC 2.3.1.6., Acetyl‐CoA:choline O‐acetyltransferase) from rat and bovine brain were investigated. The molecular weight of the enzyme from rat cerebrum was 65,000 measured by gel filtration and 66,000 measured by acrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Two species of the enzyme detected in bovine caudate nuclei were studied using the same procedures. The major transferase species, bovine I (Bov I), yielded values of molecular weights of 69,000 and 70,000, respectively. The minor bovine acetylase species (Bov II) had a molecular weight of 67,000 daltons by gel filtration. The dependence of reaction rates catalyzed by Bov I and rat choline acetyltransferase on temperature and pH was examined. The two enzymes possess apparent activation energies of 21.0 and 20.0 kcal/mol, respectively. Both displayed a rather broad pH optimum, extending into the alkaline region, and were activated by either NaCl or KCl. Neither enzyme was activated or inhibited by a wide range of concentrations of acetyl‐CoA or choline. Initial velocity studies for both enzymes indicated a sequential mechanism, in which both substrates must bind before either product is released. For Bov I, the Michaelis constants for acetyl‐CoA and choline were 16.5 μM and 0.714 mm, respectively; the equivalent constants for rat CAT were 46.5 μM and 1.0 mm. Product inhibition studies with the rat enzyme showed that acetylcholine was competitive with respect to choline, and noncompetitive with respect to acetyl‐CoA, while CoA inhibited competitively with respect to acetyl‐CoA and noncompetitively with respect to choline. The values of K1, obtained for acetylcholine and CoA were 45.5 mm and 37.7 μM, respectively.
Hippocampal Free Amino Acids in Alzheimer's Disease
Authors: Tarbit I. , Perry E. K. , Perry R. H. , Blessed G. , Tomlinson B. E. 
Published: October 2006

Abstract:The free amino acid content of the hippocampus, obtained at postmortem, has been analysed in cases of Alzheimer's disease and compared with normal cases. There were no significant differences in the levels of 23 amino acids including the transmitter candidates γ‐aminobutyric, glutamic or aspartic acids. This finding is interpreted in relation to present knowledge of transmitter pathways in the region of the hippocampus. A tendency for some amino acids to be increased in the Alzheimer group reached statistical significance for arginine. This observation is consistent with increased proteolytic or peptidase activity in Alzheimer's disease.
Cysteinesulfinic Acid Decarboxylase Activity in the Mammalian Nervous System: Absence from Axons
Authors: Sturman J. A. 
Published: October 2006

Abstract:The activity of cysteinesulfinic acid decarboxylase (CSAD, EC 4.1.1.29) in extracts of liver of seven mammals varied greatly, whereas in extracts of brain from the same species, the variation was less marked. CSAD activity was readily measured in extracts of spinal cord from the same species, except those from rhesus monkey and man. The most noteworthy observation was the complete absence of CSAD activity in extracts of optic nerves and of sciatic nerves from all seven mammals. This suggests that taurine biosynthesis does not occur within axons and that intraaxonal taurine is supplied by axonal transport from the cell body.
Aging Decreases Oxidative Metabolism and the Release and Synthesis of Acetylcholine
Authors: Gibson Gary E. , Peterson Christine 
Published: October 2006

Abstract:Acetylcholine (ACh) synthesis in vivo is known to decrease during the aging process (senescence). To elucidate the molecular mechanism(s) of this age‐related decline, we studied brain slices from 3‐, 10‐, and 30‐month‐old mice of two strains (C57B1 and Balb/c). In low K+ media, oxidative metabolism as measured by 14CO2 production decreased with aging from 100% (3 months) to 85% (10 months) or 71% (30 months) whether [U−14C]glucose, [3,4‐14C]glucose, or [l‐14C]pyruvate was the substrate. In the aged brain (3 months) the increase in 14CO2 production with K+ stimulation was about twofold higher than in the young brain (3 months). Thus, in high K+ media, only slight decreases (<10%) in oxidative metabolism occurred with aging. Changes in ACh synthesis paralleled the decreases in 14CO2 production. Synthesis of [14C]ACh from [U‐14C]glucose in low K+ media declined from 100% (3 months) to 85% (10 months) or 66% (30 months), while in high K+ media only slight decreases (<10.5%) occurred with aging. The Ca2+‐dependent, K+‐stimulated release of [14C]ACh declined from 100% (3 months) to 58% (10 months) or 25% (30 months). Only the decrease in the release of ACh declined to the same extent as the reduced in vivo synthesis of ACh with aging. The results suggest that decreases in oxidative metabolism, ACh synthesis, and in the release of ACh contribute to a reduction in cholinergic function in the senescent brain.
Release of Endogenous Amino Acids from Superior Colliculus of the Rabbit: In Vitro Studies After Retinal Ablation
Authors: Sandberg Mats , Corazzi Lanfranco 
Published: October 2006

Abstract:Tissue slices from the superior colliculi (SC) of the rabbit were superfused and investigated 1 week after unilateral eye removal. Amino acid levels were determined both in the tissue slices and in the medium after chemical depolarisation (56 mM K). The amino acid determinations were done fluorimetrically by precolumn derivation and HPLC separation. Colliculi contralateral to the enucleation exhibited a 16% reduction in glutamate compared with the ipsilateral colliculi. The Ca‐dependent release of glutamate or other amino acids tested was not appreciably affected by enucleation. However, both the total and the Ca‐independent release of glutamate was lower from contralateral SC slices compared with the ipsilateral slices. The results do not favour glutamate as the major optic nerve transmitter in the rabbit, but do not rule out glutamate as a transmitter in a minor population of retinal fibres.
Cerebroside and Sulfatide Biosynthesis in the Brain of Snell Dwarf Mouse: Effects of Thyroxine and Growth Hormone in the Early Postnatal Period
Authors: Sarlieve L. L. , Bouchon R. , Koehl C. , Neskovic N. M. 
Published: October 2006

Abstract:Snell dwarf mice (dw/dw) and normal mice (+/?) were injected with thyroxine (T4) (1 μg/animal, four injections) and growth hormone (GH) (20 μg/animal, four injections) from the 5th to the 15th day of life. In the untreated dw/dw mouse brain, the specific activities of UDP‐galactose:ceramide galactosyltransferase (CGalT), PAPS:cerebroside sulfotransferase (CST), and 2′,3′‐cyclic nucleotide 3′‐phosphohydrolase (CNP) were decreased by 28, 25, and 37%, respectively, compared with the control untreated +/? mice. The major effect of T4 was an increase of the brain CNP in the +/? mice (+40%) and dw/dw mice (+111%). The treatment with T4 also brought to normal the level of CGalT in dw/dw brain; a somewhat less marked effect on CST was observed. The treatment with GH had a great stimulatory effect on CNP: the specific activity of this enzyme increased by 40 and 69% in +/? and dw/dw mouse brain, respectively. On the contrary, no effect of GH on the CGalT activity was observe in this study. Our results suggest that T4 and GH may have both independent and complementary actions on the myelin‐associated enzymes during the early postnatal period of brain development.
Multiple Forms of Glutamate Decarboxylase in Porcine Brain
Authors: Spink David C. , Wu Susan J. , Martin David L. 
Published: October 2006

Abstract:Three forms of glutamate decarboxylase from hog brain (termed α‐, ß‐, and γ‐GAD) were separated by hydrophobic interaction chromatography on phenyl‐Sepharose, by isoelectric focusing, and by polyacryl‐amide gel electrophoresis. When rechromatographed on phenyl‐Sepharose, each form migrated as a single entity, indicating that the forms are not readily interconvertible. The three forms are not different‐sized aggregates of one form, since all three have the same approximate molecular weight (100,000) as determined by Sephadex G‐200 chromatography. The pIs of the three forms separated by phenyl‐Sepharose were determined by isoelectric focusing. The values obtained (5.3, 5.5, and 5.8 for α‐, ß‐, and γ‐GAD, respectively) were comparable to the pIs of the three peaks of activity observed upon focusing of enzyme that had been subjected to phenyl‐Sepharose chromatography. These results indicate that phenyl‐Sepharose chromatography and isoelectric focusing separate the same three components. When synaptosomal extracts were analyzed by phenyl‐Sepharose chromatography without intervening purification steps, all three forms were present, but the proportion of ß‐GAD was somewhat higher and that of γ‐GAD somewhat lower than in the usual preparations.
The Identity of Hexokinase Activities from Mitochondrial and Cytoplasmic Fractions of Rat Brain Homogenates
Authors: Needels Dwight L. , Wilson John E. 
Published: October 2006

Abstract:Cytoplasmic hexokinase (ATP: d‐hexose 6‐phosphotransferase, EC 2.7.1.1) was purified from the soluble fraction of a rat brain homogenate by a procedure that included a unique affinity elution of the enzyme from Blue Dextran‐Sepharose. The purified enzyme was examined with respect to properties in which the impure cytoplasmic enzyme has been reported to differ from the solubilized mitochondrial enzyme. These included the ability to bind to mitochondria, inhibition by quercetin, effect of pH on activity, and kinetics. In all regards the purified mitochondrial and cytoplasmic enzymes appeared identical. In addition, comparative peptide maps after partial proteolysis showed no detectable differences. These results do not support the view that there exist distinct mitochondrial and cytoplasmic forms of hexokinase, the latter being permanently relegated to a cytoplasmic location and unable to participate in a dynamic equilibrium with the mitochondrially‐bound enzyme. Alternatives are proposed to explain previous results that had been interpreted as indirect evidence for the existence of a distinct cytoplasmic hexokinase.
The Presence of Phospholipase D In Rat Central Nervous System Axolemma
Authors: DeVries George H. , Chalifour Robert J. , Kanfer Julian N. 
Published: October 2006

Abstract:An axolemma‐enriched fraction prepared from a purified myelinated axon fraction isolated from rat CNS was found to contain phospholipase D at a specific activity similar to that of a microsomal fraction isolated from whole brain. There was a concomitant threefold enrichment in the specific activity of phospholipase D and acetylcholinesterase in the axolemma‐enriched fraction compared with the specific activities of these enzymes in the starting white matter whole homogenate. This axonal phospholipase D may be involved in remodeling of phospholipid, which in turn may affect axonal functions such as ion translocation.
Effect of Colchicine on 45Ca and Choline Uptake, and Acetylcholine Release in Rat Brain Synaptosomes
Authors: O'Leary M. E. , Suszkiw J. B. 
Published: October 2006

Abstract:The effects of 1 and 10 mM colchicine on the K+‐evoked release of preformed and newly synthesized acetylcholine and on the K+‐depolarization‐stimulated uptake of 45Ca were compared in rat brain synaptosomes. Preincubation of synaptosomes with 1 mM colchicine had little effect on transmitter release and on uptake of 45Ca; 10 mM colchicine inhibited both the release of transmitter and uptake of 45Ca by 58%. Since 1 mM colchicine has been shown to disaggregate intrasynaptosomal micro‐tubules almost completely, but to be without effect on release of either preformed or newly synthesized acetylcholine in our experiments, it is concluded that colchicine modifies transmitter release by reducing Ca2+ influx, rather than by its postulated intracellular action on microtubule‐mediated transmitter mobilization. In addition, 1 and 10 mM cholchicine significantly inhibited the high‐affinity choline uptake in synaptosomes. This hemicholinium‐like action of colchicine may contribute to the reduction of transmitter release.