bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurement of very long‐chain fatty acids, phytanic and pristanic acid in plasma and cultured fibroblasts by gas chromatography
Authors: Dacremont G. , Cocquyt G. , Vincent G. 
Published: November 2004

SummaryTwo methods are described, both currently used in our laboratory, for the quantitative analysis of very long‐chain fatty acids, phytanic acid and pristanic acid in plasma and cultured fibroblasts by gas‐liquid chromatography. The first method is based on the procedure developed by Moser and Moser (1991) and the second is based on the method of Onkenhout and colleagues (1989), which is an application of the original method of Lepage and Roy for plasma and fibroblasts. A survey is given of the concentrations of very long‐chain fatty acids, pristanic and phytanic acid in plasma and fibroblasts from control subjects and all patients investigated so far in our laboratory.
Measurement of dihydroxyacetone‐phosphate acyltransferase (DHAPAT) in chorionic villous samples, blood cells and cultured cells
Authors: Wanders R. J. A. , Ofman R. , Romeijn G. J. , Schutgens R. B. H. , Mooijer P. A. W. , Dekker C. , van den Bosch H. 
Published: November 2004

SummaryDihydroxyacetone‐phosphate acyltransferase (DHAPAT) is a peroxisomal enzyme catalysing the first step in ether‐phospholipid biosynthesis. DHAPAT is deficient in cells from patients suffering from a variety of peroxisomal disorders. Accurate measurement of the activity of this enzyme is of great importance, especially since it is a central parameter in the prenatal diagnosis of the disorders of peroxisome biogenesis, rhizomelic chondrodysplasia punctata and DHAPAT‐deficiency. We describe a straightforward and accurate assay allowing the activity of DHAPAT to be measured reliably in chorionic villus samples, blood cells, cultured skin fibroblasts, cultured chorionic villus fibroblasts and cultured amniocytes.
Immunoblot analysis of peroxisomal proteins in liver and fibroblasts from patients
Authors: Wanders R. J. A. , Dekker C. , Ofman R. , Schutgens R. B. H. , Mooijer P. 
Published: November 2004

SummaryIdentification of a patient as suffering from a peroxisomal disorder usually starts by the finding of elevated very long‐chain fatty acids in plasma and/or serum. This is followed by more detailed studies in blood, fibroblasts and tissues, including immunoblot analysis. Indeed, immunoblot analysis has become a valuable tool in the correct diagnosis and assignment of individual patients, except for X‐linked adrenoleukodystrophy (X‐ALD). We describe a simple immunoblotting procedure applicable to liver and fibroblast homo‐genates using antibodies raised against catalase and the three β‐oxidation enzyme proteins acyl‐CoA oxidase I, bifunctional protein and peroxisomal thiolase. The same procedure can also be used for chorionic villus biopsy specimens and has now become the method of choice for the prenatal diagnosis of Zellweger syndrome (and other disorders of peroxisome biogenesis) and rhizomelic chondrodysplasia punctata.
Secondary alterations of human hepatocellular peroxisomes
Authors: De Craemer D. 
Published: November 2004

SummaryThe morphological and morphometric characteristics of peroxisomes in normal human liver and the peroxisomal alterations in the liver of patients with acquired or congenital non‐peroxisomal diseases are reviewed. Secondary peroxisomal changes are observed in steatosis, hepatitis and cirrhosis induced by various agents (viruses, alcohol, drugs, etc.), in cholestasis, in hepatomas, in extrahepatic cancer with or without liver metastasis, in extrahepatic inflammatory processes, in metabolic disorders affecting metabolism of carbohydrates, lipids and lipoproteins, glycoproteins, amino acids, bilirubin or copper, and in altered thyroid hormone levels. They are recognized as a proliferation of peroxisomes (increased in number and to a lesser extent in surface density and volume density) often accompanied by a minor reduction in size (at most to 68% of the mean diameter in control livers) but very rarely by an increase in mean peroxisomal diameter, and as proliferation‐related changes in shape (tails, gastruloid cisternae, funnel‐like constrictions, elongation, protrusions) in at least a few of the peroxisomes. These secondary alterations of the peroxisomes are clearly distinguishable from the primary changes in peroxisomes observed in the liver of patients with congenital peroxisomal disorders.
A fluorimetric assay for succinic semialdehyde dehydrogenase activity suitable for prenatal diagnosis of the enzyme deficiency
Authors: Thorburn D. R. , Thompson G. N. , Howells D. W. 
Published: November 2004

SummarySuccinic semialdehyde dehydrogenase (SSAD) is an enzyme involved in the turnover of the neurotransmitter 4‐aminobutyrate (GABA). Deficiency of SSAD results in developmental delay, ataxia, seizures and 4‐hydroxybutyric aciduria. We have developed a simple fluorimetric assay for the enzyme and applied it to measurement of SSAD activity in a range of cell types often used for prenatal and postnatal diagnosis of enzyme defects. Lymphocytes from children with SSAD deficiency were found to have <5% of the activity found in lymphocytes from normal children. Heterozygotes are asymptomatic and have intermediate enzyme activities. Although SSAD activity has been detected previously in uncultured chorionic villi, we found that SSAD was not expressed in cultured chorionic villus cells nor in some fibroblast‐like amniocytes from control fetuses. Lymphocytes from fetal blood and non‐fibroblastic amniocytes have high SSAD activities, and should be suitable for prenatal diagnosis of SSAD deficiency.
The effect of hyperphenylalaninaemia on the muscarinic acetylcholine receptor in the HPH‐5 mouse brain
Authors: Hommes F. A. 
Published: November 2004

SummaryPrevious studies on the effect of hyperphenylalaninaemia on the development of the muscarinic acetylcholine receptor in the cerebrum of the rat, using α‐methylphenylalanine‐induced hyperphenylalaninaemia, have shown a gradual and steady decrease in the number of binding sites for this neurotransmitter. The HPH‐5 mouse, a phenylalanine hydroxylase mutant, can be hyperphenylalaninaemic without the use of a hydroxylase inhibitor. By employing quantitative autoradiography using [3H]quinuclinidylbenzilate to label muscarinic acetylcholine receptors, a refined analysis of this decrease in neurotransmitter binding sites can be made. The decrease was confirmed and is therefore due to the hyperphenylalaninaemiaper se and not to the use of the inhibitor. Various areas of the brain reacted differently to hyperphenylalaninaemia, from no change (putamen) to a gradual decrease (external layer of the olfactory bulb, parietal, occipital and cingulate areas of the cerebral cortex, CA1 and CA3 layer of the hippocampus) to a decrease preceded by a transient increase (frontal area of the cerebral cortex, caudate nucleus).The extent of these changes depends on the duration of exposure to hyperphenylalaninaemia as well as on the degree of brain maturation, but can even be observed in the brain of the adult mouse on a hyperphenylalaninaemic regimen for 11 days.Since the hippocampus has been shown to be involved in the long‐term storage of information, damage to this structure by hyperphenylalaninaemia may provide a clue to the global mental retardation observed in untreated PKU.
Carbonic anhydrase II deficiency in three unrelated Japanese patients
Authors: Aramaki S. , Yoshida I. , Yoshino M. , Kondo M. , Sato Y. , Noda K. , Jo R. , Okue A. , Sai N. , Yamashita F. 
Published: November 2004

SummaryThree Japanese patients with carbonic anhydrase II (CAII) deficiency from three families were described. The parents of one patient were unrelated, the parents of each of the other two patients were first cousins. All the patients had renal tubular acidosis, osteopetrosis, symmetrical cerebral calcification and mental retardation. They exhibited poor activity and poor appetite in the neonatal period, and then developed psychomotor retardation. Two of them were diagnosed as having osteopetrosis at 10 months and 36 years of age, respectively, and the other as having osteomalacia at 28 years of age. All patients had recurrent episodes of muscle weakness. The CAII enzyme activity and protein levels in red blood cells in each of the three patients were deficient. Their parents exhibited approximately 50% normal levels of CAII activity and protein.This is the first report of patients with CAII deficiency in the Japanese population.
Long‐term clinical progress in bone marrow transplanted mucopolysaccharidosis type I patients with a defined genotype
Authors: Hopwood J. J. , Vellodi A. , Scott H. S. , Morris C. P. , Litjens T. , Clements P. R. , Brooks D. A. , Cooper A. , Wraith J. E. 
Published: November 2004

SummaryTwo mucopolysaccharidosis type I (MPS‐I) patients, subjected to bone marrow transplantation (BMT) more than 10 years ago, have recently had their α‐L‐iduronidase genotypes defined. Both patients, homozygous for the relatively common W402X mutation, received BMT when they were 14 and 11 months of age, and are now 12 and 14 years old, respectively. Untreated MPS‐I patients, homozygous for W402X, have an extremely severe clinical phenotype with rapid clinical deterioration and death before 6 years of age. The 12‐year‐old patient, with limited mobility, is coping well at school, while the other patient is wheelchair‐bound with severe disability in his lower limbs, and attends a school for the physically handicapped. Both patients have less than normal intelligence with slowly continuing losses. A third MPS‐I patients, diagnosed at the age of 6 months, was felt, prior to BMT at 14 months, to have a severe phenotype. Twelve years post‐BMT, he is ambulatory, albeit with restricted movement, and has normal intelligence. This patient did not have a defined MPS‐I genotype and had α‐L‐iduronidase protein and activity consistent with a less severe outcome than the first two patients. We conclude that BMT has significantly slowed down the clinical regression of the W402X phenotype. We propose that if further gains are to be made, BMT should be performed within the first few months of life. Early diagnosis is therefore essential.
A novel mtDNA deletion in an infant with Pearson syndrome
Authors: Kapsa R. , Thompson G. N. , Thorburn D. R. , Dahl H. ‐H. M. , Marzuki S. , Byrne E. , Blok R. B. 
Published: November 2004

SummaryPearson syndrome is a multisystem mitochondrial disorder of infancy that is associated with deletions in the mitochondrial DNA (mtDNA) genome. We report a study on a male infant with Pearson syndrome. Assessment of oxidative phosphorylation activity indicated combined respiratory‐chain defects in muscle, liver and fibroblasts; in particular, activity of complex I was reduced. Analysis of the patient's mtDNA identified a novel heteroplasmic 2.461 kb deletion, present at levels greater than 50% of the total mtDNA in the tissues examined. The deletion spanned nucleotides 10368 to 12828 and was flanked by a 3 bp GCC direct repeat sequence. Gene sequences affected are subunits 3, 4, 4L and 5 of complex I, and tRNAs for arginine, histidine, serine and leucine. Our findings correlate with the multiorgan involvement observed in Pearson syndrome.
Brain magnetic resonance imaging in children with optimally controlled hyperphenylalaninaemia
Authors: Toft P. B. , Lou H. C. , Krägeloh‐Mann I. , Andresen J. , Güttler F. , Guldberg P. , Henriksen O. 
Published: November 2004

SummaryThis study was undertaken to investigate whether the white‐matter changes on MRI and the EEG abnormalities detectable in treated adolescents and adults with hyperphenylalaninaemia (HPA) can be detected in younger children on an optimally controlled diet. The study included 17 children, 7–12 years of age, with HPA. The MRI of five healthy children were included in the blind evaluation of the MR images. According to mutation genotype and dietary tolerance of phenylalanine, 9 patients have severe HPA and 8 have moderate HPA, all requiring dietary treatment. Mild white‐matter hyperintensity was detected in 1 of the 5 healthy children and in 10 of 17 patients. EEG was abnormal in 2 patients. This group of children was compared with a previously reported group of adolescents with HPA who had been treated according to the same dietary regimen. MRI changes and EEG abnormalities were significantly less frequent in the group of children than in the group of adolescents. It is suggested that the more frequent MRI changes and EEG abnormalities seen in adolescents are related to the fact that a relaxation of the dietary treatment after the age of 8 years is often accepted.
Long‐chain 3‐hydroxyacyl‐CoA dehydrogenase in chorionic villi, fetal liver and fibroblasts and prenatal diagnosis of 3‐hydroxyacyl‐CoA dehydrogenase deficiency
Authors: von Döbeln U. , Venizelos N. , Westgren M. , Hagenfeldt L. 
Published: November 2004

SummaryPrenatal diagnosis of long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency was performed by analysis of the enzyme activity in a chorionic villus biopsy obtained in the 10th week of pregnancy. The diagnosis was confirmed in liver tissue and cultured fibroblasts from the aborted fetus.
The investigation of respiratory chain disorders in heart using endomyocardial biopsies
Authors: Rustin P. , Lebidois J. , Chretien D. , Bourgeron T. , Piechaud J. ‐F. , Rötig A. , Sidi D. , Munnich A. 
Published: November 2004

ConclusionHitherto, cardiomyopathy has never been reported as the presenting symptom of a mitochondrial disorder. Although it appears premature to conclude as to the prevalence of defects of oxidative phosphorylation in hypertrophic cardiomyopathies, this study demonstrates that such defects should be regarded as a potential cause of idiopathic hypertrophic cardiomyopathy in early infancy. While an abnormal redox status in plasma and widespread multitissue defects support the diagnosis of mitochondrial cardiomyopathy, normal results in such investigations do not preclude the possibility of heart‐specific respiratory chain defect and should prompt one to carry outin vivo investigations on endomyocardial biopsies.
The blood‐brain barrier: Cellular basis
Authors: Janzer R. C. 
Published: November 2004

SummaryPerfusion experiments with horseradish peroxidase have established that the morphological substrate of the blood‐brain barrier is represented by microvascular endothelial cells. They are characterized by complexly arranged tight junctions and a very low rate of transcytotic vesicular transport. They express transport enzymes, carrier systems and brain endothelial cell‐specific molecules of unknown function not expressed by any other endothelial cell population. These blood‐brain barrier properties are not intrinsic to these cells but are inducible by the surrounding brain tissue. Type I astrocytes injected into the anterior eye chamber of the rat or onto the chick chorioallantoic membrane are able to induce a host‐derived angiogenesis and some blood‐brain barrier properties in endothelial cells of non‐neural origin. Recently we have shown that this cellular interaction is due to the secretion of a soluble astrocyte derived factor(s). Astrocytes are also implicated in the maintenance, functional regulation and the repair of the blood‐brain barrier. Complex interactions between other constituents of the microenvironment surrounding the endothelial cells, such as the basement membrane, pericytes, nerve endings, microglial cells and the extracellular fluid, take place and are required for the proper functioning of the blood‐brain barrier, which in addition is regionally different as reflected by endothelial cell heterogeneity.
Abnormalities of biogenic amine metabolism
Authors: Hyland K. 
Published: November 2004

SummaryThe term biogenic amine is an umbrella term that encompasses all amines with an origin in biological processes. This review will be restricted to the biogenic amine abnormalities that affect the metabolism of serotonin and the catecholamines. The synthesis and catabolism of these neurotransmitters are outlined, and a summary is given of the neurological details, biochemical features, and treatment of the inborn errors that primarily affect their metabolism. An idea is also developed that proposes that abnormalities of biogenic amine metabolism are far more common than is currently considered, and that the search for these problems may be appropriate in any neonate or infant who presents with neurological problems of unknown origin.
Excitotoxicity, energy metabolism and neurodegeneration
Authors: Ludolph A. C. , Riepe M. , Ullrich K. 
Published: November 2004

SummaryThere is increasing evidence that the neurotoxic effects of excitatory amino acids and their analogues are part of the pathogenesis of neuronal degeneration in acute and chronic neurological disease. Recent studies indicate that activation of excitatory amino acid receptors is also induced in the mechanism of neuronal damage induced by impairment of cellular energy metabolism. This article briefly summarizes the evidence for the presence of such a mechanism and discusses metabolic diseases in which excitatory amino acids alone or in combination with energy deficiency could play a pathogenetic role. In these and other metabolic diseases, antagonists to excitatory amino acid receptors may offer a therapeutic opportunity; however, there are potential limits that may prevent chronic use.
An introduction to the molecular basis of inherited myelin diseases
Authors: Matthieu J. ‐M. 
Published: November 2004

SummaryThe myelin sheath is an extension of a plasma membrane tightly wrapped around axons. It facilitates conduction while conserving space and energy. Myelin is characterized by a high lipid content (80% of dry weight). Most myelin proteins are unique to that structure and some of them are restricted to the central or peripheral nervous system. In this review a few examples of inherited metabolic disorders affecting the oligodendrocyte and/or the Schwann cells are presented. Emphasis is placed on mutations in animals that represent invaluable models for investigating the molecular mechanisms of inherited myelin diseases in humans.
Biochemical pathogenesis of subacute combined degeneration of the spinal cord and brain
Authors: Surtees R. 
Published: November 2004

SummaryIn humans, subacute combined degeneration of the spinal cord and brain, a primary demyelinating disease, is caused by cobalamin or methyltetrahydrofolate deficiency. Experimental studies into its pathogenesis suggest that dysfunction of the methyl‐transfer pathway may be the cause. Compelling evidence for this comes from the study of inborn errors of cobalamin metabolism where deficiency of methylcobalamin, but not deoxyadenosylcobalamin, is associated with demyelination. Recent studies have focused upon inborn errors of the methyl‐transfer pathway. Cerebrospinal fluid concentrations of metabolites of the methyl‐transfer pathway have been measured in humans with sequential errors of the pathway and correlated with demyelination demonstrated on magnetic resonance imaging of the brain. This has provided new data suggesting that deficiency ofS‐adenosylmethionine is critical to the development of demyelination in cobalamin deficiency.
Injecting and non‐injecting cocaine use in Sydney, Australia: physical and psychological morbidity
Authors: KAYE SHARLENE , DARKE SHANE 
Published: November 2004

AbstractThis study aimed to examine the physical and psychological harms of cocaine use and investigate the role of injecting versus non‐injecting routes of administration in the severity of such harms. Two hundred and twelve cocaine users from inner‐city and southwestern Sydney were administered a structured interview containing sections on demographics, drug treatment history, drug use history, cocaine use patterns, cocaine dependence and physical and psychological problems associated with cocaine use. Serious physical and psychological symptoms were prevalent among both injecting and non‐injecting cocaine users. The prevalence and extent of symptoms was greater among injecting cocaine users, however route of administration did not prove to be a significant independent predictor of harm when other factors, such as frequency of use and level of dependence, were taken into account. While the level of physical and psychological harm was greater among cocaine injectors, it would appear that factors engendered by injecting, such as more frequent use and higher levels of dependence, result in higher levels of harm, rather than the route of administration per se. Physical and psychological problems were also reported among infrequent users, suggesting that cocaine can cause harm irrespective of frequency or method of use. Harm reduction initiatives should be targeted towards all cocaine users, not just those who seek treatment for dependence or present with acute medical complications.
Usage of Antifungal Drugs for Therapy of Genital CandidaInfections, Purchased as Over‐the‐Counter Products or by Prescription: 2. Factors that May have Influenced the Marked Changes in Sales Volumes During the 1990s
Authors: Mårdh Per-Anders , Wågström Jolanta , Landgren Maria , Holmén Jan 
Published: November 2004

Background: The epidemiology of vulvovaginal candidiasis (VVC) and such recurrent infections (RVVC) has been difficult to study as the majority of episodes of these conditions are self‐treated by the women affected. In
Sweden, all pharmacies are owned by the state and all prescriptions and over‐the‐counter (OTC) products, such as antifungals, are registered in a database, which offers unique possibilities to study the epidemiology of VVC/RVVC.Objectives: To analyze all prescriptions and OTC products purchased for therapy of VVC/RVVC and to establish reasons for any observed variation in the sales figures.Methods: Sales figures in the Swedish county of Skåne of antifungal drugs for therapy of VVC/RVVC were analyzed by the aid of the ‘ACS’ database of the National Corporation of Swedish Pharmacies for the years 1990–1999. The size of the female population in the county is approximately half a million.Results: The study showed that 93% of all antifungal drugs for VVC/RVVC were sold as OTC products. An increase in sales of the drugs occurred until mid‐1993/94, followed by a decrease until end of the study period in 1999. Demographic factors (e.g. the number of female inhabitants in the county, pharmacies and health‐care
units), the pregnancy rate and pharmacy‐dependent factors (such as the introduction of shelves for selfselection of antifungal products) did not explain the observed variations in sales. Distinct short‐term variations in the number of prescriptions of fluconazole and itraconazole could be explained by drugs company sales campaigns and logistics factors in drug distribution. The sales volumes in the 33 municipalities in the county correlated with the density of the population, which was not the case for the total number of prescriptions
made in the county during the 1990s. The variation in antifungal drug sales was similar to that of hormonal intrauterine devices, but this was not the case for oral contraceptives. The total Swedish usage of antibiotics showed a similar variation to that of the antifungal drugs analyzed.Conclusion: The study stresses the limited impact on the treatment of VVC/RVVC by the medical community. Behavior‐related factors in the female population are the most likely explanation for the marked variations found in the usage of drugs for the two conditions.