bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiology and pathophysiology of organic acids in cerebrospinal fluid
Authors: Hoffmann G. F. , Meier‐Augenstein W. , Stöckler S. , Surtees R. , Rating D. , Nyhan W. L. 
Published: November 2004

SummaryConcentrations of organic acids in cerebrospinal fluid (CSF) appear to be directly dependent upon their rate of production in the brain. There is evidence that the net release of short‐chain monocarboxylic acids from the brain is a major route for removing these products of cerebral metabolism. Concentrations of organic acids in blood and CSF are largely independent of each other. Quantitative reference values for the concentrations of organic acids in CSF and plasma as well as ratios of individual organic acids between CSF and plasma were determined in 35 pairs of samples from paediatric patients. Over 25 organic acids were quantifiable in all or in the majority of CSF and/or plasma specimens (limit of detection 1 µmol/L). There were substantial differences in the CSF/plasma ratios between subgroups of organic acids. Metabolites related to fatty‐acid oxidation were present in CSF in substantially less amounts than in plasma. Organic acids related to carbohydrate and energy metabolism and to amino acid degradation were present in CSF in the same amounts as or slightly smaller amounts than in plasma. Finally, some organic acids were found in substantially higher amounts in CSF than in plasma, e.g. glycolate, glycerate, 2,4‐dihydroxybutyrate, citrate and isocitrate.Studies of organic acids in CSF and plasma samples are presented from patients with ‘cerebral’ lactic acidosis, disorders of propionate and methylmalonate metabolism, glutaryl‐CoA dehydrogenase deficiency andl‐2‐hydroxyglutaric acidura. It became apparent that derangements of organic acids in the CSF may occur independently of the systemic metabolism. Quantitative organic acid analysis in CSF will yield new information on the pathophysiology in the central nervous system (CNS) of these disorders and may prove necessary for successful monitoring of treatment of organoacidopathies, which present mainly with neurological disease. For example, in glutaryl‐CoA dehydrogenase deficiency the urinary excretion of glutarate appears to be an inadequate parameter for monitoring the effect of dietary therapy, without plasma and CSF determinations. Inl‐2‐hydroxyglutaric aciduria the elevation ofl‐2‐hydroxyglutarate was found to be greater in CSF than in plasma. In addition, some other organic acids, glycolate, glycerate, 2,4‐dihydroxybutyrate, citrate and isocitrate, were also elevated in the CSF of the patients out of proportion to normal levels in plasma and urine. High concentrations of an unknown compound, which was tentatively identified as 2,4‐dihydroxyglutarate, were found in the CSF of patients withl‐2‐hydroxyglutaric aciduria. Quantitative determination of organic acids in CSF and plasma should aid the monitoring of treatment of patients with organic acid disorders, allow investigations of metabolites in known disorders, and detect neurometabolic diseases in which the diagnostic metabolites accumulate preferentially in CSF.
Non‐ketotic hyperglycinaemia: Molecular lesion, diagnosis and pathophysiology
Authors: Tada K. , Kure S. 
Published: November 2004

SummaryNon‐ketotic hyperglycinaemia (NKH) is a well‐recognized metabolic cause of life‐threatening illness in the neonate. The fundamental defect is in the glycine cleavage system, which consists of four protein components. Our study revealed that the majority of NKH patients had a specific defect in P‐protein (glycine decarboxylase). The primary lesion of NKH at gene level was investigated, using cDNA encoding human glycine decarboxylase. A three‐base deletion resulting in deletion of Phe756 was found in a Japanese patient with NKH. The majority of NKH patients in Finland, where there is a high incidence of NKH, were found to be due to a common mutation, a point mutation resulting in the amino acid substitution of Ile564 for Ser564. Prenatal diagnosis is feasible by determining the activity of the glycine cleavage system and is also possible by DNA analysis. Recent findings suggest that a high concentration of glycine in the brain may contribute to the pathophysiology of NKH by overactivatingN‐methyl‐d‐aspartate receptors allosterically, which may result in intracellular calcium accumulation, DNA fragmentation and neuronal death. These provide the possibility that early treatment withN‐methyl‐d‐aspartate receptor antagonist may prevent brain damage in NKH.
Inherited disorders of GABA metabolism
Authors: Jakobs C. , Jaeken J. , Gibson K. M. 
Published: November 2004

SummaryGamma‐aminobutyric acid (GABA), a major inhibitory neurotransmitter in the mammalian central nervous system, is produced from glutamic acid in a reaction catalysed by glutamic acid decarboxylase. The sequential actions of GABA‐transaminase (converting GABA to succinic semialdehyde) and succinic semialdehyde dehydrogenase (oxidizing succinic semialdehyde to succinic acid) allow oxidative metabolism of GABA through the tricarboxylic acid cycle. The inherited disorders of GABA metabolism include: (1) pyridoxine‐dependent seizures (?glutamic acid decarboxylase deficiency) (>50 patients); (2) GABA‐transaminase deficiency (2 patients/1 family); (3) succinic semialdehyde dehydrogenase deficiency (32 patients/21 families); and (4) homocarnosinosis associated with serum carnosinase deficiency (3 patients/1 family). Homocarnosine is a brain‐specific dipeptide of GABA andl‐histidine. Of these four defects, definitive enzymatic diagnoses have been made only for GABA‐transaminase and succinic semialdehyde dehydrogenase deficiencies. The presumptive mode of inheritance for all disorders is autosomal recessive, and all are associated with central nervous system dysfunction. Only succinic semialdehyde dehydrogenase deficiency manifests organic aciduria, which may account for the higher number of patients identified with this disorder; identification of additional patients with some of the other disorders will require increased request for analysis of cerebrospinal fluid metabolites by paediatricians and neurometabolic specialists.
Recent developments in Menkes disease
Authors: Kodama H. 
Published: November 2004

SummaryRecent studies on Menkes disease are reviewed, focusing especially on copper transport in the cells. A large amount of copper accumulated in the organelle‐free cytoplasm, whereas mitochondria were in a state of copper deficiency, indicating that Menkes mutation probably affects copper transport from the cytosol to the organelles in the cells. Microscopic observation of the brain of the macular mouse showed that copper accumulates in the blood vessels. Observation of the brain tissue of the macular mouse after intraventricular administration of copper revealed that copper accumulates in the glia as well as the blood vessels. Copper accumulation was also observed in cultured astrocytes, a type of glial cell, indicating that the affected astrocytes accumulate blood‐borne copper and release little of it in the patients with Menkes disease. Thus the effective treatment of Menkes disease could possibly be to release trapped copper from the blood vessels and glia into the neurons.
Substrate specificity and functional characterisation of the H+/amino acid transporter rat PAT2 (Slc36a2)
Authors: Kennedy David J , Gatfield Kelly M , Winpenny John P , Ganapathy Vadivel , Thwaites David T 
Published: November 2004

Functional characteristics and substrate specificity of the rat proton‐coupled amino acid transporter 2 (rat PAT2 (rPAT2)) were determined following expression in Xenopus laevis oocytes using radiolabelled uptake measurements, competition experiments and measurements of substrate‐evoked current using the two‐electrode voltage‐clamp technique. The aim of the investigation was to determine the structural requirements and structural limitations of potential substrates for rPAT2.
Amino (and imino) acid transport via rPAT2 was pH‐dependent, Na+‐independent and electrogenic. At extracellular pH 5.5 (in Na+‐free conditions) proline uptake was saturable (Km 172±41 μM), demonstrating that rPAT2 is, relative to PAT1, a high‐affinity transporter.
PAT2 preferred substrates are L‐α‐amino acids with small aliphatic side chains (e.g. the methyl group in alanine) and 4‐ or 5‐membered heterocyclic amino and imino acids such as 2‐azetidine‐carboxylate, proline and cycloserine, where both D‐ and L‐enantiomers are transported.
The major restrictions on transport are side chain size (the ethyl group of α‐aminobutyric acid is too large) and backbone length, where the separation of the carboxyl and amino groups by only two CH2 groups, as in β‐alanine, is enough to reduce transport. Methylation of the amino group is tolerated (e.g. sarcosine) but increasing methylation, as in betaine, decreases transport. A free carboxyl group is preferred as O‐methyl esters show either reduced transport (alanine‐O‐methyl ester) or are excluded.
The structural characteristics that determine the substrate specificity of rPAT2 have been identified. This information should prove valuable in the design of selective substrates/inhibitors for PAT1 and PAT2.

British Journal of Pharmacology (2005) 144, 28–41. doi:10.1038/sj.bjp.0706029
Emerging patterns of cannabis and other substance use in Aboriginal communities in Arnhem Land, Northern Territory: a study of two communities
Authors: CLOUGH ALAN R. , D'ABBS PETER , CAIRNEY SHEREE , GRAY DENNIS , MARUFF PAUL , PARKER ROBERT , O'REILLY BRIDIE 
Published: November 2004

AbstractA recent rise in cannabis use in Indigenous communities in northern Australia may have compounded existing patterns of other substance use. This paper describes these patterns in Arnhem Land in the ‘Top End’ of the Northern Territory (NT). Economic impacts of the cannabis trade are also described. In a descriptive cross‐sectional study, random samples included 336 people (169 males, 167 females) aged 13–36 years. Consensus classification of lifetime and current use of cannabis, alcohol, tobacco, kava, inhalants (petrol) and other drugs was derived based on health workers’ proxy assessments. A sample (n = 180, aged 13–36) was recruited opportunistically for interview. Lifetime cannabis users among those interviewed (n = 131, 81 males, 50 females) described their current cannabis use, usual quantities purchased and consumed, frequency and duration of cannabis use and other substance use. In the random samples, 69% (63–75%) of males and 26% (20–31%) of females were lifetime cannabis users (OR = 7.4, 4.5–12.1, p 5 0.001). The proportion of males currently using cannabis was 67% (60–73%) while the proportion of females currently using cannabis was 22% (16–27%) (OR = 7.9, 4.8–13.1, p 5 0.001). Current cannabis users were more likely than non‐users to be also using alcohol (OR = 10.4, 4.7–23.3, p 5 0.001), tobacco (OR = 19.0, 7.9–45.8, p 5 0.001) and to have sniffed petrol (OR = 9.1, 4.6–18.0, p 5 0.001) but were less likely to be using kava (OR = 0.4, 0.2 –0.9, p 5 0.001). Among those interviewed, higher tobacco consumption in current users and greater alcohol use in lifetime users was associated with increased cannabis use. Action is required to reduce cannabis use, especially in combination with other substances.
General practitioners' role in preventive medicine: scenario analysis using alcohol as a case study
Authors: DORAN CHRISTOPHER M. , SHAKESHAFT ANTHONY P. , FAWCETT JULIA E. 
Published: November 2004

AbstractThe purpose of this analysis is threefold: first, to extract from the literature, current levels of GP detection of at‐risk drinking by their patients, rates at which general practitioners (GPs) offer an intervention; and the effectiveness of these interventions; secondly, to develop a model based on this literature to be used in conjunction with scenario analysis; and thirdly, to consider the cost implications of current efforts and various scenarios. This study deals specifically with Australian general practice. A two‐step procedure is used in the scenario analysis, which involves identifying opportunities for detection, intervention, effectiveness and assigning probabilities to outcomes. The results suggest that increasing rates of GP intervention achieves greatest benefit and return on resource use. For every 5% point increase in the rate of GP intervention, an additional 26 754 at‐risk drinkers modify their drinking behaviour at a cost of $231.45 per patient. This compares with a cost per patient modifying drinking behaviour of $232.60 and $208.31 for every 5% point increase in the rates of detection and effectiveness, respectively. The knowledge, skill and attitude of practitioners toward drinking are significant, and they can be the prime motivators in persuading their patients to modify drinking behaviour.
Reasons for cannabis use in men with and without psychosis
Authors: GREEN BOB , KAVANAGH DAVID J. , YOUNG ROSS MCD 
Published: November 2004

AbstractPsychoses are relatively low prevalence disorders that have a disproportionately negative impact on individuals and society. Cannabis use is one factor that can exacerbate the negative consequences associated with psychotic disorders. Relatively few studies have examined the effects or reasons for using cannabis self‐reported by individuals with psychosis. The present study is the first known to compare directly such factors in individuals with and without psychosis, within a single study. At baseline and follow‐up participants with psychosis most commonly reported using cannabis for positive mood alteration (36% and 42%), coping with negative affect (27% and 29%) and for social activity reasons (38% and 29%). The control group most commonly reported using cannabis for relaxation (34% and 43%) and social activity reasons (49% and 51%). Participants with psychosis were less likely to report relaxation as the most important effect after use (27%) or expect it at follow‐up (49%) compared to the control group (53% and 70%). In both groups, addiction and positive affect enhancement were the composite variable scores correlated most consistently with concurrent amount and frequency of use.
Harm reduction and the global drug control regime: contemporary problems and future prospects*
Authors: BEWLEY‐TAYLOR DAVID R. 
Published: November 2004

AbstractCountries committed to a harm‐reduction approach to drugs have exploited the latitude which exists within the UN global drug control regime to implement strategies which deviate from the strict prohibition ethos of the conventions. These nations risk pressure being brought to bear through the UN drug control regime, principally by the United States, determined to prevent what it sees as foreign challenges to its domestic ‘zero tolerance’ approach and its internationalisation. In this paper, based on his presentation to the International Conference on the Reduction of Drug Related Harm in Melbourne this year, David Bewley‐Taylor, describes the conventions and the ‘wiggle room’ which exists, but also imagines ways like‐minded states might together challenge and reform the conventions so that harm reduction can be accepted and hard wired into the UN drug control system itself.
“To Be” or “Ought To Be”: The Questions of Empirical Content and Normative Bias in Léon Walras's Methodology
Authors: Debs Alexandre 
Published: November 2004

Léon Walras was a truly revolutionary economist. Not only did he leave a lasting mark on economic doctrine participating in the Marginalist Revolution, which supplanted the labor theory of value of the classical school, but he also contributed to major changes in economic methodology as being one of the first and most ardent promoters of the use of mathematics in economics. For an actor who played such a great role in the development of economics, how did he conceive his scientific endeavor? This question can be broken down into two different but related questions: First, how did he know that he had found true scientific laws? What was his theory of knowledge? Is it best described as empiricist (claiming that all knowledge comes from experience) or idealist (claiming that reason can achieve knowledge independently of experience)? And, second, what relation did his writings on pure theory bear with his policy prescriptions? Was there a normative bias in Léon Walras's methodology, i.e., were his positive statements molded by his normative inclinations?This last set of questions has generated much debate, given that Walras actively fought for scientific rigor while not refraining from defending his views on the desired social order. For W. Jaffé, who unearthed his correspondence, a careful study of primary evidence shows that Walras's conception of justice heavily influenced his search for pure truth. TheÉléments d'économie politique pure(Éléments), “appears, on the surface, as a competelywert-frei” system, but it is nevertheless “inform[ed]” by “implicit moral convictions” (Jaffé 1977, p. 371). However, D. A. Walker has strongly attacked Jaffe's allegation that Walras's theory of general equilibrium was deliberately constructed as a normative scheme, pointing to Walras's “careful distinctions between normative and positive subject matters” (Walker 1984, p. 466).
Effects of self‐modelling on stuttering
Authors: Webber Margaret J. , Packman Ann , Onslow Mark 
Published: November 2004

AbstractBackground: The paper reports on a laboratory investigation of the effects of self‐modelling on stuttering rate in adolescents and adults. Self‐modelling refers to a therapeutic or training method, usually involving videotape, that uses exposure to oneself performing selected error‐free behaviours as the conduit for promoting behaviour change.Aims: To investigate self‐modelling in single‐subject experiments to determine whether any reductions in stuttering could be directly attributable to watching self‐modelling videotapes and to ascertain whether instruction to focus attention on the target behaviour, namely stutter‐free speech, was necessary for experimental effects.Methods & Procedures: A single‐subject withdrawal design was employed with two adult men and an adolescent boy. Speaking sessions during all phases of the study were of 3‐min duration. During the B Phase, subjects watched one of their self‐modelling videotapes, which had been edited to remove all stuttered speech, before each speaking session. In the B+C Phases, subjects continued to watch the self‐modelling videotapes before each speaking session and, in addition, were instructed to attempt to speak during the session as they had spoken on the videotape.Outcomes & Results: Stuttering reduced under self‐modelling conditions for one of the three subjects. This effect was observed during the B+C Phases, which included instruction to attend to the target behaviour.Conclusions: The study provides laboratory evidence that self‐modelling can ameliorate stuttering. The clinical implications of this finding are that treatments for adults may well benefit from the inclusion of self‐modelling procedures, and self‐modelling procedures may form a part of relapse prevention and management strategies.
PTB or Not to Be: Promiscuous, Tolerant and Bizarro Domains Come of Age
Authors: Farooq Amjad , Zhou Ming‐Ming 
Published: November 2004

AbstractPTB domains are protein modules that usually interact with the cytoplasmic tail of a wide variety of growth factor receptors. In so doing, they mediate the transduction of extracellular information to specific downstream targets within the cell that ultimately determine the fate of a number of important biological processes such as cell growth and differentiation, cell cycle regulation and apoptosis. Recent structural and functional studies of PTB domains from a variety of cellular proteins have begun to shed light on the molecular mechanisms of action of these important protein modules. In the present review, we provide an account of such studies and suggest that PTB domains can be subdivided into three distinct categories on the basis of their topological differences. We also discuss the various mechanisms employed by the PTB domains in recognition of a diverse set of ligands without a consensus sequence. Finally, we discuss the role of molecular plasticity as a possible determinant of functional versatility of PTB domains. IUBMB Life, 56: 547‐557, 2004
Serum Concentration of IL‐18 Correlates with Disease Extent in Young Children with Atopic Dermatitis
Authors: Hon Kam Lun Ellis , Leung Ting Fan , Ma Kwok Chiu , Wong Chun Kwok , Wan Helene , Lam Christopher W. K. 
Published: November 2004

Abstract:  Interleukin (IL)‐18 is a pleiotropic cytokine that plays an important role in both type 1 (Th1) and type 2 (Th2) helper T lymphocyte‐mediated immunity. Previous studies have suggested that IL‐18 may be an inflammatory marker for atopic dermatitis (AD). The purpose of our study was to test whether the serum concentration of IL‐18 is a useful inflammatory marker for assessing AD severity in young children. Nineteen AD patients with a median age of 2.2 years (interquartile range 0.7–4.6 years) were recruited. The severity of AD was clinically determined using the Scoring Atopic Dermatitis (SCORAD) index. Their SCORAD score was 23.9 (range 18.6–34.8). Serum IL‐18 levels were determined by sandwich enzyme immunoassay. The median serum concentration of IL‐18 was 394 pg/ml (interquartile range 204–612 pg/ml). Serum IL‐18 levels correlated with SCORAD scores (r = 0.502, p = 0.029) and their extent component (r = 0.633, p = 0.004). When compared with mild disease with low SCORAD scores, the serum concentration in moderate to severe disease was significantly higher (p = 0.014). We concluded that serum IL‐18 concentration is elevated in young children with AD. It may be a useful inflammatory marker that correlates with the extent component of AD in particular, and differentiates mild disease from more severe disease when used for assessing AD severity in young children.
Spacing and Competition Between Planted Grass Plugs and Preexisting Perennial Grasses in a Restoration Site in Oregon
Authors: Huddleston Russell T. , Young Truman P. 
Published: November 2004

Abstract Planting native species into restoration settings where other natives already occur is a common practice. However, the competitive consequences of such plantings are rarely studied. Planting density also affects restoration costs. Here we examined the effects of established individuals of Lemmon's needlegrass (Achnatherum lemmonii) on plugs of bluebunch wheatgrass (Pseudoroegneria spicata) and Idaho fescue (Festuca idahoensis) in a restoration site in Oregon. All three of these grasses are local native perennials. Plugs were planted at 6, 12, and 18 cm from established A. lemmonii bunchgrasses and also in plots without A. lemmonii neighbors. Plug survival was uniformly high, averaging more than 98%. Plugs planted at 6 cm from established grasses showed significantly lower growth and reproduction than plugs planted at 18 cm, which had similar values to plugs not planted in the vicinity of A. lemmonii. These results suggest that interplanting distances of as little as 18 cm were sufficient to greatly reduce competitive effects on newly planted plugs, at least in early establishment at this site.