bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stepwise carcinogenesis of hepatocellular carcinoma in the cirrhotic liver: Demonstration on serial MR imaging
Authors: van den Bos Indra C. , Hussain Shahid M. , Terkivatan Türkan , Zondervan Pieter E. , de Man Robert A. 
Published: October 2006

AbstractPurposeTo demonstrate imaging findings of stepwise carcinogenesis of hepatocellular carcinoma (HCC) in cirrhosis at serial state‐of‐the‐art MR imaging exams.Materials and MethodsIn a retrospective search of the hospital archives, three patients were identified in which developing HCC was observed in serial MR examinations, with histopathology or alpha‐fetoprotein (AFP) correlation. Image findings were assessed for signal intensity of the lesions at multiple sequences, including dynamic gadolinium‐enhanced imaging.ResultsInitial findings in patient A showed a small nodule with fatty infiltration that developed in HCC in follow‐up MRI, comprised of low‐grade dysplastic nodule (DN; DN I), high‐grade DN (DN II), and eventually classic HCC. In patient B, increased signal intensity on T2‐weighted images in a single DN among numerous regenerative nodules was the only initial sign. Follow up MRI showed further increase in signal intensity and increased neovascularity, which suggested focal HCC in a DN II. Patient C demonstrated gradually increasing neovascularity as only initial sign, with development of classic HCC over time.ConclusionMR imaging provides insight in various pathways of stepwise carcinogenesis of developing HCC in cirrhosis. This may further explain the genetic heterogeneity, and may facilitate early detection and better selection of patients for follow‐up. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
FLUID COMPARTMENTATION AND ELECTROLYTES OF CAT CEREBRAL CORTEX IN VITRO–I SWELLING AND SOLUTE DISTRIBUTION IN MATURE CEREBRAL CORTEX*
Authors: Bourke Robert S. , Tower Donald B. 
Published: October 2006

SUMMARYThe distribution of indicator solutes (inulin, sucrose, raffinose, thiocyanate, chloride, and isethionate) and the swelling in slices of adult cat cerebral cortex incubated in vitro have been investigated for a variety of incubation media and conditions. Where appropriate, these data have been compared with analogous data obtained on cat cerebral cortex in vivo (Bourkeet al., 1965) and with data previously reported for slices of rat cerebral cortex (Pappius and Elliott, 1956; Pappiuset al., 1962) and guinea pig cerebral cortex (Varon and McIlwain, 1961; Keeseyet al., 1965) incubated in vitro under comparable conditions.In addition to substantial agreement of present data with previously reported in vitro data, a number of new findings have been added by the present study: (a) a component of slice swelling which is K+‐dependent; (b) the association of slice swelling with presence of a diffusible, external anion (Cl−) and its prevention by replacement with a relatively non‐diffusible anion (isethionate−); (c) variation of the size of slice chloride spaces as a direct function of slice swelling; (d) dependence of the size of slice fluid spaces accessible to inulin and sucrose upon time, during incubation, of solute addition and upon K+ concentration of the incubation medium; (e) indications of the dynamic and presumably metabolically‐dependent nature of indicator solute distribution; and (f) the mobility of a portion of the fluid of swelling associated with changing the K+ concentration but not the tonicity of the medium during incubation.At least five operationally‐defined fluid compartments may be inferred from the present data : (1) interstitial or extracellular space(s) readily accessible to all solutes and of a size which can be minimally estimated from direct determinations in viuo; (2) additional fluid space(s) accessible to most solutes, including inulin and sucrose, under apparently suboptimal conditions of slice metabolism in vitro; (3) fluid space(s) prone to swell under in vitro conditions and readily accessible in vitro to chloride and thiocyanate but not to inulin or sucrose; (4) fluid space(s) which swell reversibly in the presence of added external K+ (or Rb+) and are inaccessible to all usual indicator solutes; and (5) after exclusion of the foregoing, the remaining fluid presumably comprising most of the intracellular space(s).The data have been discussed in terms of the morphological complexity of cerebral cortex, in terms of applicability to studies of cortical electrolyte distribution, and in terms of the general problem of delineating cerebral interstitial spaces.
THE EFFECTS OF PRECURSOR LOADING IN THE CEREBRAL METABOLISM OF 5‐HYDROXYINDOLES
Authors: Moir A. T. B. , Eccleston D. 
Published: October 2006

Abstract—Using either tryptophan or 5‐hydroxytryptophan as the precursor, and examining the metabolites in whole rat brain and in brain regions of dog, the pattern of metabolites resembled that found under physiological conditions only after tryptophan administration. From these and other observations on the cerebral 5‐hydroxyindoles the main conclusions are firstly, that there are regional differences within brain in storage, turnover or metabolic fate of 5‐HT. Secondly, that the normal pathway appears to be well localized biochemically with linking of its succeeding steps, and thirdly, that turnover through the system is normally controlled by intracerebral tryptophan 5‐hydroxylase in both rats and dogs although there are differences between the species in the cerebral metabolism of 5‐HT.
THE EFFECTS OF ANOXIA UPON ENERGY SOURCES AND SELECTED METABOLIC INTERMEDIATES IN THE BRAINS OF FISH, FROG AND TURTLE1
Authors: McDougal D. B. , Holowach J. , Howe M. C. , Jones E. M. , Thomas C. A. 
Published: October 2006

Abstract—The levels of the main cerebral energy reserves, ATP, P‐creatine, glycogen and glucose, and of several glycolytic intermediates and lactate, were measured in the brains of fish (Carassius auratus), turtle (Pseudemys scripta elegans) and frog (Rana pipiens). The levels of glycogen in these brains were 2‐9 times higher than those reported for mammals. In frog, cerebral glycogen levels were 35 per cent higher during the winter than in spring. The P‐creatine: ATP ratios were 3 instead of the more usual (mammalian) value of 1. The levels of other intermediates were similar to those found in mammalian brain.When anoxia was produced by decapitation, changes in the various substances measured were similar to those in mammalian brain, but were much slower. The initial rate at which high‐energy phosphate was used could be calculated from these changes. Values of 1.1 m‐equiv./kg/min for fish and frog and of 0.46 m‐equiv./kg/min for turtle were found, which are 1/20 and 1/50, respectively, of the rate in mouse brain. The rate of disappearance of high‐energy phosphate reserves followed first‐order kinetics for 4 hr in turtle and for at least an hour in the other species.Changes in metabolites as the experiment progressed were interpreted to indicate a progressively falling intracellular pH, prolonged inhibition of phosphofructokinase, and a long period of hexokinase inhibition.
THE EFFECTS OF A THIAMINE ANTAGONIST, PYRITHIAMINE, ON LEVELS OF SELECTED METABOLIC INTERMEDIATES and ON ACTIVITIES OF THIAMINE‐DEPENDENT ENZYMES IN BRAIN and LIVER1
Authors: Holowach Jean , Kauffman F. , Ikossi Maria G. , Thomas Charlotte , McDougal D. B. 
Published: October 2006

Abstract—(1) The effects of thiamine deficiency as produced by pyrithiamine injections have been studied in the weanling mouse. Selected metabolites were measured in extracts from brain and liver of quick‐frozen animals. Pyruvate and α‐oxoglutarate dehydrogenases and transketolase were also measured.(2) In deficient brain, pyruvate and α‐oxoglutarate levels were greatly increased. Xylulose‐5‐P and 6‐P‐gluconate were more than doubled. Lactate, glucose‐6‐P, glucose and P‐creatine were moderately elevated, and ATP was increased a little. Glutamate was depressed.(3) In deficient liver, α‐oxoglutarate was much increased and ATP was twice normal. Glycogen, glucose, glucose‐6‐P, 6‐P‐gluconate, pyruvate, and glutamate were not different from the controls. Lactate was depressed.(4) Pyruvate dehydrogenase activity was reduced to 25 per cent or less in brain and liver. Transketolase and α‐oxoglutarate dehydrogenase activities were reduced to 50 per cent in both organs.(5) Thiamine treatment, within 5 hr, largely reversed the metabolite changes brought on by pyrithiamine in brain. At the same time pyruvate and α‐oxoglutarate dehydrogenase activities were increased 60 per cent or more in both brain and liver. Transketolase activity in liver was only increased 20 per cent at this time, however, and in brain was unchanged.(6) The results are interpreted to indicate that inhibition of pyruvate and α‐oxoglutarate dehydrogenases in brain is sufficient to depress in vivo function. The same seems true for the inhibition of α‐oxoglutarate dehydrogenase in liver. However, the changes seen in brain 6‐P‐gluconate and xyluIose‐5‐P probably depend on factors other than, or in addition to, the decrease in transketolase activity. It seems worthy of emphasis that in spite of the partial metabolic blocks high‐energy phosphate stores were actually increased.
GLYCOGEN, AMMONIA AND RELATED METABOLITES IN THE BRAIN DURING SEIZURES EVOKED BY METHIONINE SULPHOXIMINE1
Authors: Folbergrová Jaroslava , Passonneau Janet V. , Lowry O. H. , Schulz D. W. 
Published: October 2006

Abstract— The levels of ATP, P‐creatine, glucose, glycogen, lactate, glutamate and ammonia were measured in mouse brain after administration of the convulsive agent methionine sulphoximine (MSO). No changes were observed in ATP and P‐creatine levels either before or during the seizures. Lactate levels were unchanged until the onset of seizures (4–5 hr) at which time the levels increased an average of 65 per cent. Glucose and glycogen levels increased progressively. Just before the onset of seizures the levels had increased 95 and 62 per cent, respectively. During the seizures both substances had increased a total of 130 per cent. Comparable changes were found in cerebral cortex, cerebellum and subcortical forebrain. Through the use of quantitative histochemical methods it was found that the greatest increases in glycogen occurred in layers I and III (layers II and IV were not analysed). Progressively smaller changes were found in layers V and VI and no increase at all was found in the subjacent white matter. Glucose, in contrast to glycogen, increased to about the same degree in all cerebral layers and in subjacent white matter.The increase in glycogen after MSO administration may be related to the fact that MSO also causes an increase in the ratio of brain to serum glucose levels. This would indicate that an increase in intracellular glucose had occurred.Ammonia levels were increased 300–400 per cent in both cerebrum and cerebellum. A time study in cerebellum showed that the increase begins early and reaches maximal levels long before the onset of seizures. Glutamate levels were reduced by small but statistically significant amounts in both cerebrum and cerebellum. Administration of methionine sulphoximine completely prevented seizures and the increase in lactate, but did not prevent the increases in glycogen and glucose. The rise in ammonia was reduced but not prevented.During 20 sec of complete ischaemia (decapitation) ATP, P‐creatine and glucose fell somewhat more rapidly than normal in brain of animals undergoing MSO seizures. From the changes it was calculated that the metabolic rate had been increased about 20 per cent by the seizure.A new sensitive and specific enzymic method for determination of tissue ammonia is presented together with evised enzymic procedures for lactate and glutamate.
A COMPARATIVE STUDY OF BRAIN AND LIVER MITOCHONDRIA FROM NEW‐BORN AND ADULT RATS
Authors: Gregson N. A. , Williams P. L. 
Published: October 2006

Abstract—

A method has been developed for the estimation of organelle number in subcellular fractions and applied to the estimation of the mitochondrial content of brain and liver from new‐born and adult rats.
The respiratory enzyme content per mitochondrion of the adult brain was 3·5 times greater than that of the neonate. This increase in enzyme content was not correlated with an increase in the mean size of the organelle.
The succinate dehydrogenase activity per mitochondrion of the livers from neonatal and adult rats showed no obvious change. There was, however, an increase in the mean size of the organelle.
These findings are discussed with reference to the development of the brain and to the development of mitochondria.
PROPERTIES AND REGIONAL DISTRIBUTION OF HISTIDINE DECARBOXYLASE IN RAT BRAIN
Authors: Schwartz J. C. , Lampart C. , Rose C. 
Published: October 2006

Abstract—Properties of the histamine‐forming enzyme in rat brain were studied, utilizing a sensitive fluorometric assay. The optimum pH was related to substrate concentration and found to be6·4 at 10−2m‐histidine; the apparent Km was about 4·10−4m; enzyme activity was inhibited by α‐hydrazino ‐histidine and brocresine but was not affected by α‐methyl DOPA or benzene. These different data suggest that the 'specific’histidine decarboxylase (EC 4.1.1.22)—and not the aromatic l‐aminoacid decarboxylase—is involved. Determination of enzyme activity and histamine level in different areas of the rat brain revealed important regional differences, the two values being roughly parallel.
REGIONAL DISTRIBUTION AND RATE OF PRODUCTION OF FREE FATTY ACIDS IN RAT BRAIN
Authors: Bazán N. G. , de Bazán Haydeé E. P. , Kennedy Wendy G. , Joel C. D. 
Published: October 2006

Abstract— We have found the levels of free fatty acids (FFA) in rat brain to be much lower than had been previously supposed.An unusually rapid and linear production of FFA occurred in brains of adult rats during the period from 30 s to 4 min after decapitation. Under the same conditions the production of FFA in the brain of the newborn rat or in the liver or spleen of the adult rat was much slower. The major sources of the FFA produced in the brain of the adult rat under these conditions were lipids other than triglycerides. FFA, like norepinephrine, occurred in much higher concentration in the hypothalamic region and the brain stem than in the remainder of the brain.We have proposed a hypothesis suggesting that norepinephrine might regulate membrane‐associated processes in the central nervous system by stimulating the enzymic splitting of the polar lipids of neuronal membranes. This action of norepinephrine might be mediated by adenosine 3′,5′‐phosphate in a manner analogous to that by which norepinephrine stimulates the enzymic splitting of triglycerides in adipose tissue.Liquid nitrogen and Freon‐12 have been compared for their respective efficacies in the rapid freezing of rat brain in situ.
METABOLISM OF THE ASPARTYL MOIETY OF N‐ACETYL‐l‐ASPARTIC ACID IN THE RAT BRAIN
Authors: Nadler J. V. , Cooper J. R. 
Published: October 2006

AbstractThe metabolism of N‐acetyl‐l‐aspartic acid (NAA) was studied in rat brain. [Aspartyl‐U‐14C]NAA was metabolized predominantly by deacylation. Studies of NAA biosynthesis from l‐[U‐14C]aspartic acid have confirmed previous reports that NAA turns over slowly in rat brain. However, intracerebrally‐injected N‐acetyl‐l‐[U‐14C]asparticacid was rapidly metabolized. Exogenous NAA appears to be taken up rapidly into a small, metabolically‐active pool. This pool serves as substrate for a tricarboxylic acid cycle associated with the production of glutamate for the biosynthesis of glutamine. The bulk of the NAA content in brain appears to be relatively inactive metabolically.
THE RELATIVE SIGNIFICANCE OF CO2‐FIXING ENZYMES IN THE METABOLISM OF RAT BRAIN
Authors: Patel M. S. 
Published: October 2006

AbstractTo evaluate the relative significance of CO2‐fixing enzymes in the metabolism of rat brain, the subcellular distribution of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, NADP‐isocitrate dehydrogenase and NADP‐malate dehydrogenase, as well as the fixation of H14CO3− by the cytosol and the mitochondria was investigated. Pyruvate carboxylase and phosphoenol‐pyruvate carboxykinase are mainly localized in the mitochondria whereas NADP‐isocitrate dehydrogenase and NADP‐malate dehydrogenase are present in both the cytosol and the mitochondria. In the presence of pyruvate rat brain mitochondria fixed H14CO3− at a rate of about 170 nmol/g of tissue/min whereas these organelles fixed negligible amounts of H14CO3− in the presence of α‐ketoglutarate or phosphoenolpyruvate. Rat brain cortex slices fixed H14CO3− at a rate of about 7 nmol/g of tissue/min and it was increased by two‐fold when pyruvate was added to the incubation medium. The carboxylation of α‐ketoglutarate and pyruvate by the reversal of the cytosolic NADP‐isocitrate dehydrogenase and NADP‐malate dehydrogenase respectively was very low as compared to that by pyruvate carboxylase. The rate of carboxylation reaction of both NADP‐isocitrate dehydrogenase and NADP‐malate dehydrogenase was only about 1/10th of that of decarboxylation reaction of the same enzyme. It is suggested that under physiological conditions these two enzymes do not play a significant role in CO2‐fixation in the brain. In rat brain cytosol, citrate is largely metabolized to α‐ketoglutarate by a sequential action of aconitate hydratase and NADP‐isocitrate dehydrogenase. The operation of the citrate‐cleavage pathway in rat brain cytosol is demonstrated. The data show that among four CO2‐fixing enzymes, pyruvate carboxylase, an anaplerotic enzyme, plays the major role in CO2‐fixation in the brain.
COMPARTMENTATION OF AMINO ACID METABOLISM IN THE RAT POSTERIOR PITUITARY
Authors: Minchin M. C. W. , Beart P. M. 
Published: October 2006

Abstract—Isolated rat posterior pituitary glands were incubated with [14C]glucose or [14C]acetate and the incorporation of radioactivity into several amino acids was followed. The results indicated that radioactivity was incorporated from [14C]glucose into a large pool of glutamate which appeared to be responsible for a large proportion of GABA synthesis in the gland. The specific activity of glutamine was always less than that of glutamate when [14C]glucose was the precursor employed, whereas [14C]acetate labelled a glutamate pool which had approximately the same specific activity as that of glutamine. The results are discussed with reference to the compartmentation of amino acid metabolism in the nervous system.
THE BINDING OF TRIETHYLTIN TO RAT BRAIN MYELIN
Authors: Lock E. A. , Aldridge W. N. 
Published: October 2006

Abstract—A high affinity binding site for triethyltin was found in rat brain myelin with an affinity of approx 6·6 × 105m−1 at pH 7·5. Competitive binding studies showed that triethyl‐lcad had about the same affinity and trimethyltin 30 times lower affinity than triethyltin. Hexachlorophane and 3,5‐diiodo‐4′‐chlorosalicylanilide did not prevent triethyltin binding to rat brain myelin. Since triethyltin, hexachlorophane and 3,5‐diiodo‐4′‐chlorosalicylanilide all produce similar oedematous lesions in the brain of rats, whereas triethyl‐lead and trimethyltin do not, it is concluded that the high affinity triethyltin binding site either is not involved or is not the only factor in oedema production.
THE EFFECT OF HCO3− ON THE SWELLING AND ION UPTAKE OF MONKEY CEREBRAL CORTEX UNDER CONDITIONS OF RAISED EXTRACELLULAR POTASSIUM
Authors: Bourke R. S. , Kimelberg H. K. , West C. R. , Bremer A. M. 
Published: October 2006

Abstract— Increasing the HCO3− concentration of incubation media containing raised K+ concentrations (18‐71 mm) caused increased swelling of monkey cerebral cortex slices. This swelling was mainly associated with increased intracellular levels of Na+ and Cl− ions. It was independent of the type of buffer used and was not a result of the increased Na+ concentration in the media due to added HCO3− or the increased osmolarity. The levels also were unaffected by alteration of the pH in the range of 6·9‐ 7·8 or pCO2 in the range of 3–81 mm Hg.The anatomical locus of this HCO3− stimulated swelling appeared in electron micrographs to be an expanded glial compartment. The significance of these findings is discussed in terms of the transport processes involved and the role of glial cells in maintaining correct cerebro‐cortical ion balances under normal and pathological conditions.
HIGH AFFINITY CHOLINE UPTAKE: IONIC AND ENERGY REQUIREMENTS
Authors: Simon J. R. , Kuhar M. J. 
Published: October 2006

Abstract— High affinity choline uptake into rat hippocampal synaptosomes was examined at 37°C when various ions were deleted from normal Kreb's‐Ringer media. When sodium chloride was replaced by sucrose, lithium chloride, cesium chloride or rubidium chloride, choline uptake was markedly reduced. When the sodium concentrations of the Kreb's media were gradually reduced to zero, the uptake was gradually reduced in parallel. A kinetic analysis performed at low and normal sodium concentrations revealed changes in Km and Vmax values.When several non‐chloride sodium salts were utilized, the uptake was reduced in all cases suggesting also a chloride‐dependence in addition to the sodium‐dependence. Omission of calcium chloride or magnesium sulfate from the media did not alter uptake.Sodium‐dependent choline uptake was examined over a range of potassium concentrations (0–35 DIM). It was found that uptake was maximal between potassium concentrations of 0.35–4.8 mm but was reduced at both lower and higher potassium concentrations. The kinetics of uptake were examined under varying potassium concentrations, and at low potassium, only a change in Vmax was observed while at high potassium concentrations, there were changes in both Km and Vmax values.Preincubation and incubation of synaptosomes with 0.1 m‐ouabain, 0.1 mm‐2,4‐dinitrophenol and 1 mm‐KCN caused a reduction in sodium‐dependent uptake. When dextrose was omitted from the preincubation and incubation media there was also a reduction in sodium‐dependent uptake. By contrast, the sodium‐independent uptake was unaffected by the metabolic inhibitors or omission of dextrose, and had a very low Q10. When various incubation temperatures were utilized in uptake experiments, the Q10 for the interval 37‐27°C was 2.7 and the activation energy was 22.7 kcal/mol.Slightly different ionic dependences were observed when animals pretreated with pentobarbital of oentylenetetrazol were utilized as the source of synaptosomes.
MOUSE NEUROBLASTOMA CELL ADENYLATE CYCLASE: REGULATION BY 2‐CHLOROADENOSINE, PROSTAGLANDIN E1 AND THE CATIONS Mg2+, Ca2+ AND Mn
Authors: Blume A. J. , Foster Carolyn J. 
Published: October 2006

Abstract—Some basic kinetic properties of adenylate cyclase in cell free preparations of mouse neuroblastoma were investigated. Production of cAMP from ATP by the enzyme requires the presence of either Mg2+ or Mn2+ in addition to ATP. In the presence of Mg2+, the Km for ATP is 120 ± 15 μM and the interaction of ATP and adenylate cyclase appears to be non‐cooperative (Hill coefficient of 1). Magnesium ion concentrations in excess of the ATP concentration cause stimulation although similar excess concentrations of Mn2+ cause inhibition.Prostaglandin E1 and 2‐chloroadenosine activate the enzyme. The Km of the cyclase for 2‐chloroadenosine is 6 μm. Activation by 2‐chloroadenosine leads to an increase in Vmax but does not effect the Km for ATP. At a fixed ATP concentration, the extent of activation caused by prostaglandin E1 and 2‐chloroadenosine is inversely related to the Mg2+ concentration.Calcium ion causes inhibition of adenylate cyclase from 0.1 to 4mM with a Ki of 5 ± 10−4m. Ca2+ interaction with the enzyme in the absence or presence of either 2‐chloroadenosine or prostaglandin E1 appears cooperative (i.e. Hill coefficients of ˜2). Ca2+ inhibition is non‐competitive with respect to either ATP or 2‐chloroadenosine but is progressively diminished by increasing Mn2+ concentrations.Divalent cation effects and activation by 2‐chloroadenosine and prostaglandin E1 of the neuroblastoma adenylate cyclase are compared with ion effects and hormone activation of the enzyme obtained from non‐neuronal tissue.