bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presence and maturity of dendritic cells in melanoma lymph node metastases
Authors: Polak Marta E , Johnson Penny , Palma Silvana Di , Higgins Bernie , Hurren Jeremy , Borthwick Nicola J , Jager Martine J , Mccormick Deirdre , Cree Ian A 
Published: June 2005

AbstractImmune avoidance mechanisms play a key role in the successful dissemination of melanoma. One mechanism whereby this could be achieved is by interfering with dendritic cell (DC) presentation of tumour‐associated antigens to naïve T cells. In particular, immature DCs characterized by the absence of accessory molecules are known to be immunosuppressive and to be involved in the induction of tolerance. The present study has investigated the presence and activation status of DCs within melanoma metastases in the regional lymph nodes. Using image analysis techniques, the expression of Factor XIIIa (FXIIIa), CD40, CD83 and HLA‐DR and the morphological features of DCs were examined in paraffin sections from 26 lymph nodes containing melanoma metastases. DCs expressing FXIIIa were found in 70% of the lymph nodes. The number of DCs identified was generally small but there were more concentrated areas of DCs designated as hotspots. In these areas of high FXIIIa staining, the percentage area occupied by DCs varied between 0.1% and 10%. The majority of FXIIIa‐positive cells did not express the DC maturation markers CD83 or CD40 and morphologically were rounded with few dendrites, indicating that they were immature. The cells did, however, express high levels of HLA‐DR, suggesting that they have the ability to present antigen but lack the accessory molecules required to initiate an immune response. Immature DCs, characterized by phenotypic and morphological features, are therefore present within the tumour deposits in lymph nodes infiltrated by melanoma and may specifically modulate the anti‐melanoma immune response. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Proteomic analysis of synaptosomes using isotope‐coded affinity tags and mass spectrometry
Authors: Schrimpf Sabine P. , Meskenaite Virginia , Brunner Erich , Rutishauser Dorothea , Walther Pascal , Eng Jimmy , Aebersold Ruedi , Sonderegger Peter 
Published: June 2005

AbstractSynaptosomes are isolated synapses produced by subcellular fractionation of brain tissue. They contain the complete presynaptic terminal, including mitochondria and synaptic vesicles, and portions of the postsynaptic side, including the postsynaptic membrane and the postsynaptic density (PSyD). A proteomic characterisation of synaptosomes isolated from mouse brain was performed employing the isotope‐coded affinity tag (ICAT) method and tandem mass spectrometry (MS/MS). After isotopic labelling and tryptic digestion, peptides were fractionated by cation exchange chromatography and cysteine‐containing peptides were isolated by affinity chromatography. The peptides were identified by microcapillary liquid chromatography‐electrospray ionisation MS/MS (μLC‐ESI MS/MS). In two experiments, peptides representing a total of 1131 database entries were identified. They are involved in different presynaptic and postsynaptic functions, including synaptic vesicle exocytosis for neurotransmitter release, vesicle endocytosis for synaptic vesicle recycling, as well as postsynaptic receptors and proteins constituting the PSyD. Moreover, a large number of soluble and membrane‐bound molecules serving functions in synaptic signal transduction and metabolism were detected. The results provide an inventory of the synaptic proteome and confirm the suitability of the ICAT method for the assessment of synaptic structure, function and plasticity.
Fair trade and ethical trade: are there moves towards convergence?
Authors: Smith Sally , Barrientos Stephanie 
Published: June 2005

AbstractFair trade and ethical trade have traditionally had quite different aims, scope and modalities, the former principally focused on terms of trade with small scale producers and the latter on working conditions in mainstream production. Global value chain analysis suggests that this coincided with different forms of governance in the chain: fair trade reflecting relational governance based on trust and mutual dependence, while ethical trade was incorporated into the industrial coordination of buyer‐driven, modular value chains. This paper explores the potential for greater synergy between the two as a result of recent developments, taking UK supermarket value chains as a case study. We conclude that convergence may occur in some supermarket chains, in a context of relational governance, while in others ethical trade and fair trade will remain inherently different. Whether and how convergence occurs will depend largely on the prevailing culture, values and strategies of the supermarket concerned. Copyright © 2005 John Wiley & Sons, Ltd and ERP Environment.
The role of magnetic resonance spectroscopy in the investigation of lactic acidosis and inborn errors of energy metabolism
Authors: Gadian D. G. , Leonard J. V. 
Published: June 2005

SummaryMagnetic resonance spectroscopy (MRS) provides a non‐invasive method of investigating disordered energy metabolismin vivo. Here, we briefly outline some MRS studies of skeletal muscle and brain metabolism that have been carried out in patients with inborn errors of energy metabolism. We concentrate in particular on the use of1H MRS for the detection of elevated brain lactate in these patients.
Liver enzyme activities in hyperphenylalaninaemia due to a defective synthesis of tetrahydrobiopterin
Authors: Dhondt J. ‐L. , Cotton R. G. H. , Danks D. M. 
Published: June 2005

AbstractThis report confirms the accumulation of neopterin and the low biopterin concentration in the liver of a “biopterin‐synthetase” deficient patient. Enzymatic studies suggest that the defect lies between the “X”‐compound (6‐pyruvoyl‐tetrahydropterin?) and tetrahydrobiopterin and that pterin found in the patient's liver arises from the “X”‐compound.
Brain amino acid abnormalities in pyruvate carboxylase deficiency
Authors: Perry T. L. , Haworth J. C. , Robinson B. H. 
Published: June 2005

AbstractAmino acids were measured in several regions of autopsied brain from an infant who died with congenital lactic acidosis due to pyruvate carboxylase deficiency (McKusick 26615), as well as in cerebrospinal fluid (CSF) and plasma of four living infants with this disorder. Glutamine content was greatly reduced in all brain regions, while glutamic acid and proline contents were elevated. The γ‐aminobutyric acid (GABA) content was normal in brain. Glutamine concentrations in CSF and plasma were also decreased in the living patients. Glutamine may serve as a pool to provide glutamate and GABA for use as neurotransmitters, and to provide α‐ketoglutarate for the tricarboxylic acid cycle when oxaloacetate can no longer be formed directly from pyruvate.
Pipecolic acid levels in serum and urine from neonates and normal infants: Comparison with values reported in Zellweger syndrome
Authors: Govaerts L. , Trijbels F. , Monnens L. , van Raay‐Selten A. 
Published: June 2005

AbstractPipecolic acid (PA) excretion from normal newborn, preterm and/or small‐for‐dates infants has been determined and correlated with gestational age, sex and age after birth. An effect of fetal sex was not detectable. Only small‐for‐dates infants with a gestational age of >34–37 weeks had a lower urinary excretion of PA than the appropriate‐for‐dates infants with the same gestational age. Preterm infants had a higher excretion of PA than term neonates. PA excretion of infants decreases with age after birth. This higher excretion in “younger” infants can be explained by a higher serum concentration and less efficient tubular reabsorption. PA level in serum and urine remains a valuable tool for the confirmation of the clinical diagnosis of Zellweger syndrome when gestational age and age after birth are taken into consideration. No PA was detected in serum or urine of four children suffering from hyperthyroidism.
Propionic acidaemia presenting with pancytopaenia in infancy
Authors: Sweetman L. , Nyhan W. L. , Cravens J. , Zomer Y. , Plunket D. C. 
Published: June 2005

AbstractA 2‐month‐old infant presented with vomiting, lethargy and pancytopaenia. She was found to have propionic acidaemia, and the activity of propionyl‐CoA carboxylase in cultured fibroblasts was defective (McKusick 23200). Abnormal amounts of glycine, 3‐hydroxypropionate, methylcitrate, tiglylglycine, propionylglycine, 2‐methylacetoacetate, 2‐methyl‐3‐hydroxybutyrate, 3‐oxovalerate and 3‐hydroxyvalerate were found in body fluids. It appears that the organic acidaemia leads to an inhibition in the maturation of cells in the bone marrow.
Comparison of the substrate 4‐Methylumbelliferyl‐α‐l‐iduronide with phenyl‐α‐l‐iduronide for the diagnosis of Hurler's disease in cultured cells
Authors: Butterworth J. , Broadhead D. M. 
Published: June 2005

Abstract4‐Methylumbelliferyl‐α‐l‐iduronide provided a more sensitive method than phenyl‐α‐l‐iduronide for the estimation of α‐l‐iduronidase in cultured cells and could be used to diagnose Hurler's disease. The 4‐methylumbelliferyl derivative was no more useful than the phenyl derivative for the detection of heterozygotes. All ten lysosomal enzymes tested could be used as reference enzymes when cell extracts were prepared by freeze/thawing in distilled water, but onlyN‐acetyl‐β‐d‐glucosaminidase could be used for extracts prepared by freeze/thawing in formate buffer pH 3.5 containing 150 mmol/l sodium chloride.
Metabolism of collagen in aspartylglycosaminuria: Urinary excretion of hydroxyproline
Authors: Näntö‐Salonen K. , Autio S. , Härö E. , Kivimäki T. , Koskela S. ‐L. , Näntö V. , Penttinen R. 
Published: June 2005

AbstractAspartylglycosaminuria (AGU) is a lysosomal storage disorder of glycoprotein degradation characterized by severe mental retardation and connective tissue alterations. We have previously described low collagen production in skin fibroblast cultures from AGU patients. In the present work we showed that the urinary excretion of hydroxyproline (total, non‐dialysable and free hydroxyproline as indicators of collagen metabolism) was reduced in young AGU patients in comparison with age‐matched controls. In adult patients no significant difference was detected. The results support the view that reduced collagen production is associated with the connective tissue abnormalities in this disorder.
Biotinidase deficiency: Clinical course and biochemical findings
Authors: Schubiger G. , Caflisch U. , Baumgartner R. , Suormala T. , Bachmann C. 
Published: June 2005

AbstractThe biotin responsive late‐onset multiple carboxylase deficiency (McKusick 25327) has recently been shown to be due to biotinidase deficiency (EC 3.5.1.12; Wolfet al., 1983a). This affects the regeneration of biotin from biocytin so that biotin is not available for the mitochondrial carboxylases. In consequence the metabolism of propionylcoenzyme A, 3‐methylcrotonylcoenzyme A and pyruvate is hampered. Symptoms which are considered to be characteristic of this condition are muscular hypotonia, ataxia, seizures, alopecia and seborrhoeic dermatitis. We report a case who presented only with exanthema and seizures during an acute febrile illness.
Cholesterol and prostaglandin synthesis by cultured human skin fibroblasts in the alagille syndrome involving paucity of interlobular bile ducts
Authors: Dupont J. , Raulin J. , Gautier M. , Lapous D. , Loriette C. , Kuan S. , Stewart J. , Krumhardt B. 
Published: June 2005

SummaryChildren with Alagille syndrome show high serum cholesterol (15–20 mmol/L). To establish correlation of this unusual level of cholesterol with the regulation of cholesterol metabolism, 3‐hydroxy‐3‐methylglutaryl‐CoA reductase (HMGR) activity and synthesis of cholesterol, fatty acids and acidic steroids from [14C]acetate were determined in cultured skin fibroblasts from 2–3‐year old children. Prostaglandin E2 (PGE2) synthesis and nucleic acid synthesis were determined in cells when they were growing in medium containing normal, Alagille or fetal bovine serum. These values were similar to values of controls.HMGR activity was found to be similar in cells of control and children with the syndrome, whether the cells were incubated in lipoprotein‐deficient or normal medium. Incorporation of acetate into cholesterol was inhibited to a greater extent by lipoprotein‐containing medium in control than in children with the syndrome. Fatty acid synthesis was similar in all conditions. 1–7% of the recovered lipid radioactivity in cells and medium separated as acidic steroids.Serum from a donor patient, when included in the medium, did not affect PGE2 or nucleic acid synthesis compared with normal human or fetal bovine serum. The data suggest that cells of children with Alagille syndrome may have a membrane defect of transfer of cholesterol (LDL receptor defect) leading to excessive cholesterol synthesis. Also, synthesis of acidic steroids (bile acid‐like material) and their secretion into the medium occurs in normal fibroblasts and those from children with the syndrome.
Complementation studies in human and caprine β‐mannosidosis
Authors: Hu P. , Wenger D. A. , van Diggelen O. P. , Kleijer W. J. 
Published: June 2005

SummaryCell fusions were performed to investigate the possible involvement of different gene mutations in five patients with isolatedβ‐mannosidosis and a patient with a combined deficiency ofβ‐mannosidase and heparan sulphate sulphamidase. In none of the combinations of cell lines wasβ‐mannosidase activity restored in the fused cell culture. Similarly, no complementation of sulphamidase activity was observed after fusion of cells with the combined deficiency and cells with isolated sulphamidase deficiency (mucopolysaccharidosis type IIIA). The absence of complementation suggests that the combined deficiency is not caused by a defect in one common factor affecting the two enzymes: The results rather indicate a rare coincidence of two independent mutations which are allelic with the mutation in the respective conditions with isolated enzyme deficiencies.
Prospective prevention of neonatal hyperammonaemia in argininosuccinic acidura by arginine therapy
Authors: Donn S. M. , Thoene J. G. 
Published: June 2005

AbstractArgininosuccinic aciduria, due to deficiency of argininosuccinic acid lyase, is generally associated with severe neonatal hyperammonaemia and its neurological sequelae. The cases of two siblings with this autosomal recessive disorder are presented. Both infants were preterm and delivered by Caesarean section for maternal pre‐eclampsia. The first infant was not diagnosed until after the development of severe hyperammonaemia and, despite adequate treatment with haemodialysis and arginine infusion, remained comatose for a prolonged period. At 20 months she has profound developmental delays and intellectual impairment. The second infant, whose diagnosis was made antenatally by amniotic fluid analysis, was treated with arginine infusion beginning at 32 h of life and never developed hyperammonaemia. We conclude that early recognition and prompt institution of arginine therapy is an effective regimen for the prevention of neonatal hyperammonaemia in argininosuccinic aciduria.
An unusual aminoacidopathy associated with mitochondrial encephalomyopathy
Authors: Perry T. L. , Hansen S. , Booth F. A. , Penn A. M. W. , Jones K. , Dilling L. A. 
Published: June 2005

SummaryFive patients from two unrelated pedigrees are affected by an inherited form or forms of mitochondrial encephalomyopathy in which the exact site of the block in the respiratory chain has yet to be identified. All five patients regularly exhibit an unusual aminoacidopathy evident both in fasting plasma and in CSF. Alanine concentrations are elevated, reflecting high tissue pyruvate and lactate levels. Concentrations of the four essential amino acids threonine, methionine, tryptophan and lysine are substantially reduced, as are those of citrulline, ornithine and arginine. This pattern of amino‐acid deficiency is apparently not due to failure to absorb the dibasic amino acids, to any abnormality of the urea cycle, to excessive synthesis and turnover of creatine, or to protein malnutrition. The aminoacidopathy presumably is a metabolic consequence of one or more impairments in the electron transport chain in mitochondria. A detailed explanation of its aetiology needs to be sought.
Transport inhibition in the pathology of phenylketonuria and other inherited metabolic diseases
Authors: Pratt O. E. 
Published: June 2005

AbstractKinetic analysis of the rates of transport of amino acids and of sugars across the blood‐brain barrier shows how severe is the competition which commonly occurs between groups of chemically related substances in the blood plasma for one of a number of shared transport carriers. In view of the possible importance of such competition in causing brain damage in inherited metabolic diseases an example is given of the use of these kinetic data to work out the best way of ensuring an adequate supply of amino acids to the brain during the dietary treatment of phenylketonuria. Indications are obtained of the degree to which the supply of amino acids other than phenylalanine to the brain may be reduced and of the conditions which are likely to prove most dangerous. It is concluded that the supplementation of the diet with tyrosine alone cannot be expected to provide an effective alternative to phenylalanine restriction. The high level of phenylalanine found commonly in untreated phenylketonuria carries a risk of reducing the supply to the brain of up to eleven other amino acids which the brain cells need. A lack of any one of these may interfere with brain growth and development. The implications are considered for possible improvements in the treatment of phenylketonuria or other inherited metabolic diseases. It is concluded that there may well be some advantage in increasing the intake of amino acids other than the restricted phenylalanine which the brain has to obtain from the circulation above the amounts currently given in the treatment of phenylketonuria (or of analogous compensatory nutrition in the treatment of other metabolic defects by dietary restriction).
Experience with non‐ketotic hyperglycinaemia in Finland
Authors: Von Wendt L. , Similä S. 
Published: June 2005

AbstractBy the end of 1981 a total of 28 infants suffering from non‐ketotic hyperglycinaemia had been diagnosed in Finland. The mean incidence in Finland is 1:55 000 newborns. All these infants represent the neonatal type, characterized by onset of rapidly progressing neurological symptoms during the first days of life. Attempted therapy, including strychnine, did not alter the clinical course, which in the majority of cases led to the death of the infants within the first weeks of life. Although the clinical condition appears to be normal at birth in these infants, the EEG is already pathological, and the CSF glycine level is as high as in fully developed NKH. Consequently, there is most probably prenatal brain damage in the neonatal type of NKH. The heterozygotes for NKH differ from healthy controls by significantly higher levels of plasma and urinary glycine, but a considerable overlap of individual values reduces the usefulness of this finding for active heterozygote diagnosis.
Stable isotope dilution analysis of 3‐hydroxyisovaleric acid in amniotic fluid: Contribution to the prenatal diagnosis of inherited disorders of leucine catabolism
Authors: Jakobs C. , Sweetman L. , Nyhan W. L. , Packman S. 
Published: June 2005

AbstractA quantitative assay for 3‐hydroxyisovaleric acid in amniotic fluid was developed using D6‐3‐hydroxyisovaleric acid as an internal standard. 3‐Hydroxyisovaleric acid was isolated by liquid partition chromatography and the amount determined by selected ion monitoring, ammonia chemical ionization gas chromatography‐mass spectrometry of the trimethylsilyl derivatives. The concentration of 3‐hydroxyisovaleric acid in ten normal amniotic fluids was 4.52±1.73 µmol/l. The level was elevated eight‐fold in the amniotic fluid from a pregnancy resulting in the birth of a child with biotin‐responsive multiple carboxylase deficiency. The stable isotope dilution assay of 3‐hydroxyisovaleric acid in amniotic fluid is a rapid, sensitive and accurate method for the prenatal diagnosis of this disorder, and may be of value in the prenatal diagnosis of other inherited disorders of leucine catabolism.
Malonyl coenzyme a decarboxylase deficiency
Authors: Brown G. K. , Scholem R. D. , Bankier A. , Danks D. M. 
Published: June 2005

AbstractA patient is described with a deficiency of the mitochondrial enzyme, malonyl CoA decarboxylase — an inborn error of metabolism not recognized previously. The enzyme defect was first suspected because of persistent excretion of malonic and methylmalonic acids in urine in a child with repeated episodes of vomiting, some requiring hospitalization. Disturbances of lipid metabolism were demonstrated.
Substrate specificity of manganese‐activated prolidase in control and prolidase‐deficient cultured skin fibroblasts
Authors: Butterworth J. , Priestman D. 
Published: June 2005

AbstractSkin fibroblasts have a single enzyme, Mn2+‐activated prolidase, that hydrolyses a range of amino acid‐proline dipeptides. Two cases of prolidase deficiency showed a marked loss of activity against glycyl‐proline irrespective of Mn2+ conditions. However, the abnormal enzyme showed only moderate reductions in activity against phenylalanyl‐, alanyl‐, and leucyl‐proline following preincubation with Mn2+ or addition of Mn2+ with the substrate. Control prolidase was stable to prolonged preincubation with Mn2+, whereas the abnormal prolidase was progressively inactivated. The findings indicate, for at least the present two cases, that prolidase deficiency results from an altered rather than a marked reduction in the amount of normal enzyme.
Non‐ketotic hyperglycinaemia in a family with an unusual phenotype
Authors: Ando T. , Nyhan W. L. , Bicknell Joan , Harris Ruth , Stern J. 
Published: June 2005

AbstractA 10‐year‐old girl, one of three affected sisters, with non‐ketotic hyperglycinaemia is described. In contrast to other reported cases, the course of the disorder was comparatively mild in this family. The only clinical signs were mental retardation and abnormalities in the EEG; blood glycine levels were 2–3 times normal. In the propositus, the formation of14CO2 from glycine‐1‐14C and of FH414CH2OH from glycine‐2‐14C were impaired, shown by the decreased14CO2 content of expired air and diminished labelling of carbon 3 of serine. However, the biochemical defect was no less than that seen in patients with much more severe clinical effects.
Diagnosis of the mucopolysaccharidoses using cultured skin fibroblasts and amniotic fluid cells
Authors: Butterworth J. 
Published: June 2005

AbstractAssay ofα‐L‐iduronidase, heparin sulphamidase,N‐acetyl‐α‐D‐glucosaminidase, arylsulphatase B,α‐L‐fucosidase,β‐glucuronidase,β‐galactosidase andα‐D‐mannosidase in cultured cells is described. Activities in deficient fibroblast strains are compared to control fibroblast strains. The first case of Sanfilippo B in the United Kingdom is reported. A comparison of enzyme activities in cultured fibroblasts and amniotic fluid cells is made.