bluuebunny/crossref_metadata_2025_split huggingface dataset:
Indoleamine Metabolism in Rat Brain Studied Through Measurements of Tryptophan, 5‐Hydroxyindoleacetic Acid, and Indoleacetic Acid in Cerebrospinal Fluid
Authors: Young Simon N. , Anderson George M. , Purdy William C. 
Published: October 2006

Abstract:Tryptophan, 5‐hydroxyindoleacetic acid (5HIAA), and indoleacetic acid (IAA) were measured in rat cerebrospinal fluid (CSF) using high‐performance liquid chromatography with fluorometric detection in order to study brain indoleamine metabolism. Previously we have shown that IAA in CSF is derived from tryptamine in the CNS. In this study our results indicated that the synthesis of both 5‐hydroxytryptamine (5HT) and tryptamine varied with changes in brain tryptophan. After a tryptophan load, tryptamine synthesis increased much more than 5HT synthesis; under these circumstances, it can be of the same order of magnitude as 5HT synthesis. Studies with treatments that cause release of 5HT (reserpine and cold stress) indicated that tryptamine is not released with 5HT and is probably not stored in vesicles. Use of selective monoamine oxidase inhibitors suggested that results obtained in vitvo concerning the substrates for monoamine oxidase A and B apply in vivo. Thus, 5HT was acted on preferentially by the A enzyme, and tryptamine by the B enzyme. Measurement of IAA in brain, CSF, and plasma before and after probenecid indicated that there are active transport systems moving IAA from CSF and brain to blood, and from brain to CSF. Our data suggest that measurements of CSF IAA are a simple and convenient way of studying CNS tryptamine metabolism and should be applied clinically.
Characterization of an Adenylate Cyclase‐Linked Serotonin (5‐HT1) Receptor in a Neuroblastoma × Brain Explant Hybrid Cell Line (NCB‐20)
Authors: Berry‐Kravis Elizabeth , Dawson Glyn 
Published: October 2006

Abstract:Clonal cell line NCB‐20 (a hybrid of mouse neuroblastoma N18TG2 and Chinese hamster 18‐day embryonic brain expiant) expressed both high‐ (KD 180 nM) and low‐affinity (>3000 nM) binding sites for [3H]serotonin (5‐HT) which were absent from the parent neuroblastoma. The low‐affinity binding site was eliminated by 1 μM spiperone. The order of drug potency for inhibition of high‐affinity [3H]5‐HT binding was consistent with a 5‐HT1 receptor (5,6 ‐ dihydroxytryptamine = 5‐HT = methysergide = 5‐methoxytryptamine > cyproheptadine = clozapine = mianserin > spiperone > dopamine = morphine = ketanserin = norepinephrine). [3H]5‐HT binding was inhibited by guanine nucleotides (e.g., GTP and Gpp(NH)p), whereas antagonist binding was not; as‐corbate was also inhibitory. A 30‐min exposure of cells to 1—2 μM 5‐HT or other agonists produced a three‐ to fivefold stimulation of cyclic AMP levels. The order of potency for 5‐HT agonist stimulation of basal cyclic AMP levels and 5‐HT antagonist reversal of agonist‐stimulated levels was the same as the order of drug potency for inhibition of high‐affinity [3H]5‐HT binding, suggesting linkage of the 5‐HT1 receptor to adenylate cyclase in NCB‐20 cells.
Inhibition of Calcium Uptake, Sodium Uptake, and Catecholamine Secretion by Methoxyverapamil (D600) in Primary Cultures of Adrenal Medulla Cells
Authors: Corcoran James J. , Kirshner Norman 
Published: October 2006

Abstract:The calcium‐entry antagonist D600 (methoxyverapamil) inhibited nicotine‐ and veratridine‐induced ‐45Ca‐4 uptake, 22Na+ uptake, and catecholamine secretion in primary cultures of bovine adrenal medulla cells. Inhibition of nicotine‐induced effects occurred at D600 concentrations approximately 3‐10‐fold lower than those needed to produce similar inhibition of veratridine‐induced effects. Inhibition of the veratridine‐induced effects was competitive, but inhibition of the nicotine‐induced effects was not competitive. These re‐sults suggest that D600, in addition to blocking “slow” Ca‐ channels and tetrodotoxin‐sensitive Na+ channels also blocks nicotine transmission, possibly either by noncompetitively inhibiting the interaction of nicotine with the receptor binding site or by blockade of the receptor‐associated ion conductance channel.
Positional Distribution of Acyl and Alk‐1‐enyl Groups in Grey and White Matter Ethanolamine and Choline Phosphoglycerides of a Marsupial, the Koala (Phascolarctos cinereus)
Authors: Naughton Joan M. , Trewhella Maurice A. 
Published: October 2006

Abstract: The major phosphoglycerides in grey and white matter from the brain of the koala have been separated and examined. The major polyunsaturated fatty acids present in both the diacyl‐ and alk‐1‐enyl acylglycerophosphorylethanolamines from grey matter were 22:6ω3, 20:4ω6, and 22:4ω6. In both grey and white matter, 22:6ω3 and 20:4ω6 were concentrated in the 2‐position of diacylglycerophosphorylethanolamines and 22:4ω6 in the 2‐position of alk‐1‐enylacylglycerophos‐phorylethanolamines; polyunsaturated fatty acid levels were higher in diacylglycerophosphorylethanolamines. Ethanolamine phosphoglyceride fractions from grey matter were enriched in polyunsaturated fatty acids compared with those from white matter. The acyl groups 18:0, 18:1, and 16:0 and their alk‐1‐enyl analogues were prominent in grey and white matter ethanolamine phosphoglycerides; 18:1 was dominant in white matter alk‐1‐enylacylglycerophosphorylethanolamines. The plasmalogen composition of ethanolamine phosphoglycerides was 55% in grey matter and 76% in white matter.Choline phosphoglycerides contained negligible plasmalogen and low polyunsaturated fatty acid levels. Diacylglycerophosphorylcholine was characterized by high levels of 16:0 and 18:1. Similar acyl group distributions were estimated in the 1‐position in both grey and white matter, 16:0 being present at >50%.The presence of the molecular species 18:0/22:6ω3 was indicated in grey matter diacylglycerophosphorylethanolamine, 18:1/18:1 in white matter alk‐1‐enylacylglycerophosphorylethanolamine, and 16:0/18:1 in white matter diacylglycerophosphorylcholine.
β‐Glucosidase and β‐Galactosidase in Primary Cultures of Rat Astrocytes: Comparison to the Brain Enzymes
Authors: Hof Liselotte , Kimelberg Harold K. 
Published: October 2006

Abstract:In primary astrocyte cultures β‐glucosidase (EC 3.2.1.21) and β‐galactosidase (EC 3.2.1.23) showed pH optima and Km values identical to rat brain enzymes, using methylumbelliferyl glycosides and labeled gluco‐and galactocerebrosides as substrates. The activities of both glycosidases increased in culture up to 3–4 weeks. In rat brain only galactosidase increased; glucosidase activity declined between 12–20 days after birth. The specific activities were two‐ to sixfold higher in astrocyte cultures than in rat brain. These activities were not due to uptake of enzymes from the growth medium. Secretion of β‐galactosidase, but not β‐glucosidase nor acid phosphatase could be demonstrated. These results support the suggestion of a degradative function for astrocytes in the brain.
Specific Inhibition of Dopamine D‐1‐Mediated Cyclic AMP Formation by Dopamine D‐2, Muscarinic Cholinergic, and Opiate Receptor Stimulation in Rat Striatal Slices
Authors: Kelly Eamonn , Nahorski Stefan R. 
Published: October 2006

Abstract The ability of different receptors to mediate inhibition of cyclic AMP accumulation due to a variety of agonists was examined in rat striatal slices. In the presence of 1 mM 3‐isobutyl‐1‐metbylxanthine, dopamine D‐2, muscarinic cholinergic, and opiate receptor stimulation by RU 24926, carbachol, and morphine (all at 10−‐8‐−1(10−‐5M), respectively, inhibited the increase in cyclic AMP accumulation in slices of rat striatum due to dopamine D‐1 receptor stimulation by 1 μM SKF 38393. In contrast, these inhibitory agents were unable to reduce the ability of a number of other agonists, including isoprenaline, prostaglandin E1, 2‐chloroadenosine, vasoactive intestinal polypeptide, and cholera toxin, to increase cyclic AMP levels in striatal slices.These results suggest that in rat striatum either (a) dopamine D‐2, muscarinic cholinergic, and opiate receptors are only functionally linked to dopamine D‐l receptors or that (b) the D‐1 and D‐2 receptors linked to adenylate cyclase lie on the cells, distinct from other receptors capable of elevating striatal cyclic AMP levels.
Kinetics of the Hydrolysis of 8‐Bromo‐Cyclic GMP by the Light‐Activated Phosphodiesterase of Toad Rods
Authors: Barkdoll A. E. , Pugh E. N. , Sitaramayya A. 
Published: October 2006

AbstractThe hypothesis that cyclic GMP is the internal transmitter of retinal rod phototransduction, when combined with the observations that 8‐bromo‐cyclic GMP opens the cyclic GMP‐dependent outer segment conductance and that rods into which 8‐bromo‐cyclic GMP has been injected still respond to light, predicts that the light‐activated phosphodiesterase (EC 3.1.4.17) must catalyze the hydrolysis of 8‐bromo‐cyclic GMP. This hypothesis was tested by measuring light‐activated toad rod disk membrane phosphodiesterase with a pH assay technique. Phos‐phodiesterase‐catalyzed hydrolysis of 8‐bromo‐cyclic GMP was confirmed: at pH 8.0, total proton production after flash activation was identical to total amount of 8‐bromo‐cyclic GMP added as substrate. Photoactivated phosphodiesterase was remarkably less efficient in catalyzing the hydrolysis of 8‐bromo‐cyclic GMP than of cyclic GMP: Vmax for 8‐bromo‐cyclic GMP was 0.063 M/M rhodopsin/s, whereas that for cyclic GMP was 11 M/M rhodopsin/s—170 times greater. The Km for 8‐bromo‐cyclic GMP was 160 nM, and for cyclic GMP, 590 μM. 8‐Bromo‐cyclic GMP competitively inhibited phosphodiesterase‐catalyzed hydrolysis of cyclic GMP with a Ki of 1.2 mM. Complete reaction progress curves were analyzed for obedience to Michaelis‐Menten kinetics: cyclic GMP hydrolysis, 8‐bromo‐cyclic GMP hydrolysis, and cyclic GMP hydrolysis in the presence of 8‐bromo‐cyclic GMP as competitive inhibitor were found to follow the integrated form of the Michaelis‐Menten equation over the time course of the reactions, assuming phosphodiesterase was activated as a step. The kinetic parameters extracted from reaction progress curves were consistent with those derived from analysis of the initial velocity. Our results lead to quantitative predictions about the photocurrents of rods into which 8‐bromo‐cyclic GMP and cyclic GMP are infused: these predictions are discussed.
Regulation of Central Cholecystokinin Recognition Sites by Guanyl Nucleotides
Authors: Wennogle L. , Wysowskyj H. , Steel D. J. , Petrack B. 
Published: October 2006

AbstractGuanyl nucleotides affected the binding of radio‐labeled cholecystokinin (CCK) octapeptide to rodent cortical binding sites. Micromolar quantities of a stable GTP analogue, guanylyl‐imidodiphosphate (GppNp), resulted in a plateau where binding was decreased by 30%. In the presence of 25 μM GppNp, binding analysis revealed a decrease in affinity (increase in KD), without an apparent effect on the maximal number of binding sites. Ki values for CCK‐related peptides shifted up to 1.6‐fold. The rate of peptide association decreased by threefold, and the rapid component of peptide dissociation increased. The collective data suggest that a class of central CCK binding sites is linked to nucleotide regulatory proteins. The evidence is discussed with regard to multiple receptor populations and to possible interconversions between receptor types.
Interactions of the Complex Secretory Vesicle Binding Protein Chromobindin A with Nucleotides
Authors: Martin William H. , Creutz Carl E. 
Published: October 2006

Abstract:Chromobindin A is a large, multisubunit protein that binds to chromaffin granule membranes in a Ca2+‐ and ATP‐regulated manner. Ca2+ stimulates binding to the membrane, whereas ATP, in the absence of Ca2+, is required for release of the protein from the membrane. We now report that spectral and HPLC data indicate that nucleotides are associated with the native chromobindin A complex and that the protein can bind two molecules of [3H]ATP in vitro. Chromobindin A also appears to be a novel nucleotide triphosphatase. ATPase activity was detected in fractions containing chromobindin A isolated by affinity chromatography, gel filtration, or ion exchange chromatography. Kinetic studies indicated that the Vmax is 44 nmol of Pi/mg/min and the Km is 0.115 mM, whereas the nonhydrolyzable ATP analog 5′‐adenylylimidodiphosphate acts as a competitive inhibitor of this reaction with a Ki of 0.08 mM. The activity was found to be sensitive to protease treatment or to preincubation at 65°C and was inhibited by Ca2+ or low pH. The ATPase activity was not inhibited by N‐ethylmaleimide, N,N'‐dicyclohexylcarbodiimide, vanadate, oligomycin, or azide.
Late Pleistocene History of Coniferous Woodland in the Mohave Desert
Authors: Wells Philip V. , Berger Rainer 
Published: October 2006

Seventeen ancient wood-rat middens, ranging in radiocarbon age from 7400 to 19,500 years and to older than 40,000 years, have been uncovered in the northeastern, north-central, southeastern, and southwestern sectors of the Mohave Desert. Excellent preservation of macroscopic plant materials (including stems, buds, leaves, fruits, and seeds) enables identification of many plant species growing within the limited foraging range of the sedentary wood rat .
An approximately synchronous zonal differentiation of vegetation in response to a gradient of elevation on limestone in the northeastern Mohave Desert is apparent from the macrofossil evidence, preserved in wood-rat middens and ground-sloth coprolites, covering a time span bracketed by radiocarbon ages of about 9000 and 10,000 years. Xerophilous juniper woodlands descended to an elevation of 1100 meters, some 600 meters below the present lower limit of woodland (1700 meters) in the latitude of Frenchman Flat. But desert or semidesert shrubs coexisted with the woodland trees throughout much of the span of elevation corresponding to the pluvial lowering of the woodland zone, and the more mesophytic phase of pinyon-juniper woodland was evidently confined to montane habitats at elevations above 1500 meters. Joshua trees, accompanied by desert shrubs, prevailed down to about 600 meters at Gypsum Cave, Nevada, but only the shrubs of the existing warm-desert vegetation occurred at 530 meters near Rampart Cave, Arizona .
Pleistocene middens from the southeastern Mohave Desert record a relatively large downward shift of the pinyon-juniper woodland zone, paralleling the remarkably low minimum elevation of the existing woodland zone in that area. The macrofossil evidence speaks for former continuity of the many disjunct stands of woodland vegetation in the Mohave Desert region, at least along the higher divides connecting most of the ranges. However, there is no macrofossil evidence of pluvial continuity of range for the more mesophytic, montane, coniferous-forest zone of ponderosa pine or white fir now occupying islands of relatively mesic environment on the highest mountains of the region. On the contrary, the uneven stocking of the lofty mountains of the Mohave Desert with mesophytic or boreal species and the trend toward endemism suggest a long history of isolation.
Stanford School of Medicine (1): Problems over More than Money
Authors: Walsh John 
Published: October 2006

Since World War II the American medical school has become a highly complex institution and, like other American institutions today, the medical school is being challenged to respond to diverse and often conflicting demands. In part the pressure comes from activists who insist that the medical school more fully meet the needs of the community by reforming both training and the delivery of medical care. But another sort of pressure is exerted as a result of changes in internal relationships that have occurred in the last two decades in large measure because of the federal support of biomedical research. As in most institutional conflicts the dispute is expressed in contests over power and money, but, at a more fundamental level, what is involved is the value and reward system of academic medicine and the question of how the medical school is to be governed.
This is the first of three articles which will attempt to discuss these issues in the context of the development of one medical school—Stanford's. The first article will describe the pattern and policies of expansion since World War II, and the other two will examine the effects of internal and external pressures for change.
Isospin in Nuclei
Authors: Robson D. 
Published: October 2006

The major feature of isospin in nuclei that I have discussed here is its application to all nuclei. The rebirth of this quantum number in nuclear physics occurred in the early 1960's and was initiated almost entirely by the important work of Anderson
et al.
and Fox
et al.
. There is still great interest in the use of isospin in its fullest sense as predicted by Wigner, and indeed isospin concepts have been largely responsible for demonstrating that nuclei in the doubly "magic number" region of
208
Pb are remarkably in agreement with shell model theory.

The early experiments have also initiated a whole new set of more sophisticated experiments (some of which I have briefly alluded to above) which promise to keep many physicists busy for a long time to come. A particularly interesting series of experiments are those being performed at Duke University with high-resolution proton beams. This work shows the highly detailed nature of analogue resonances, that is, as coherent superpositions of many complicated compound states yielding a beautifully modulated wave train, the modulation being observed only in conventional experiments with poor-resolution proton beams. Similarly, nuclear theorists have been led to vastly improve their interpretation of, and computational techniques for, both nuclear reactions and nuclear structure in order to meet the more stringent tests provided by such experiments.
Perhaps a lesson can be learned from the historical development of the isospin concept. In the past the belief that T ⋅ T would not significantly commute with the dynamical Hamiltonian so that isospin would not be conserved sufficiently well enough certainly delayed the nuclear travels of isospin into the realm of heavy nuclei. Hopefully the same mistake will not occur in the future for other approximate symmetries of nature.
Role of Commercial Aircraft in Global Monitoring Systems
Authors: Steinberg Robert 
Published: October 2006

The role of commercial aircraft in monitoring meteorological parameters and atmospheric constituents has been limited in the former case and virtually nonexistent in the latter. I have tried to point out that this situation can and should be changed now. The new family of wide-bodied jets such as the 747, DC-10, and L-1011 aircraft can be used to supply important global atmospheric and tropical meteorological data for which there is a pressing need. While scientists are not in total agreement on the magnitude of the effect of particulates and gases on the atmosphere, there is almost unanimous concurrence that we are severely limited in information, and that global baseline concentrations must be established for particulates and gases in the troposphere and lower stratosphere as soon as possible. Also, more synoptic meteorological information from the tropical troposphere is highly desirable.
In the final analysis, commercial aircraft may offer the most inexpensive way to monitor our atmosphere in the near future. Much of the instrumentation technology is here and the rest is certainly within our grasp. The fact of the matter is that there are now over 220 Boeing 747's and Douglas DC-10's in service, flying an average of 10 hours a day. Long-range flights, such as those from Tokyo to Anchorage to London in the Northern Hemisphere and from Hawaii to Pago Pago to Sydney in the Southern Hemisphere, are commonplace. These aircraft are equipped with inertial navigation systems and central air data computers coupled to advanced data storage systems which can readily be interrogated by satellite. This means that there is now a large amount of snyoptic weather information which can be obtained with a minimum of effort and cost. Likewise, a start at obtaining measurements of atmospheric constituents on a global basis can be made now. All we need to do is make the effort.
Departments and Disciplines: Stasis and Change
Authors: Straus Robert 
Published: October 2006

Because I believe that the departmental power base of universities has been a major factor in resisting inevitable and continuing changes in the disciplinary boundaries of research and teaching, I predict that significant changes in the nature of departments are inevitable. Departments will either permit, or even seek, a realignment of their spheres of control over disciplinary activity or they will lose the power of control over basic academic decisions and rewards.
To the extent that society at large expresses resistance to change, the status quo of departments may have a temporary lease on life. On the other hand, society's current disenchantment with academia may make radical internal change seem vital to the maintenance of public support, and even the survival of universities, and thus hasten changes in either departmental structure or departmental power. Within universities, resistance to such change is generally supported on the assumption that academic freedom will be threatened. Obviously, all change involves some risk, but a very significant limitation to academic freedom already exists in the pressures that many departments exert on members to restrict their intellectual activity to fit the departmental mold. Departments can regain their important role in fostering both academic freedom and academic responsibility for excellence if they will redefine their discipline-oriented identities and realign their priorities to include cross-disciplinary inquiry and teaching and greater responsiveness to the responsibilities and expectations of the university and society.