bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prenatal diagnosis of systemic disorders of the respiratory chain in cultured amniocytes and chorionic villus fibroblasts by studying the formation of lactate and pyruvate from glucose
Authors: Wanders R. J. A. , Wijburg F. A. , Ruiter J. , Trijbels J. M. F. , Ruitenbeek W. , Sengers R. C. A. , Bakkeren J. A. J. M. , Feller N. 
Published: June 2005

SummaryFormation of lactate and pyruvate from glucose was studied in cultured amniocytes and chorionic villus fibroblasts from controls, either untreated or treated with azide, an inhibitor of cytochromec oxidase, or other inhibitors of the mitochondrial respiratory chain. Amniocytes with an established cytochromec oxidase deficiency were also investigated.Control amniocytes treated with azide as well as cytochromec oxidase deficient amniocytes displayed strongly increased lactate‐to‐pyruvate ratios after incubation with glucose, compared to control cells. Elevated lactate‐to‐pyruvate ratios were also found in chorionic villus fibroblasts in which complexes I, III or IV were inhibited by rotenone, antimycin or azide, respectively. We conclude that measurement of lactate and pyruvate production from glucose in cultured amniocytes and/or chorionic villus fibroblasts allows adequate prenatal diagnosis of systemic cytochromec oxidase deficiency and presumably of other systemic deficiencies of mitochondrial respiratory chain enzymes.
Effect of methylmalonate onin vitro lactate release and carbon dioxide production by brain of suckling rats
Authors: Wajner M. , Dutra J. C. , Cardoso S. E. , Wannmacher C. M. D. , Motta E. R. 
Published: June 2005

SummaryMethylmalonate (MMA) accumulates in the tissues of patients with methylmalonic acidaemia, who present severe neurological signs soon after birth and later mental retardation. Attempting to understand the pathophysiology of the disorder, we investigated the effects of MMA on brain glucose uptake, lactate release and CO2 production. Glucose uptake and lactate release were studied by incubating 40 µm wide brain prisms from 15‐day‐old rats in Krebs‐Ringer bicarbonate buffer, pH 7.0, containing 5.0 mmol/L glucose and one of three concentrations of MMA (1.0, 2.5 and 5.0 mmol/L). Controls did not contain MMA in the incubation medium. MMA induced a significant increase of lactate production in a dose‐dependent pattern that was proportional to glucose uptake by the brain prisms. We also studied the influence of MMA on brain CO2 production from [2‐14C]glucose and [U‐14C]acetate by incubating brain prisms in the same buffer in the presence of the substrates with (experimental groups) or without (controls) 5.0 mmol/L MMA. MMA significantly reduced CO2 formation from both substrates.
Carrier detection for Sjögren‐Larsson syndrome
Authors: Kelson T. L. , Craft D. A. , Rizzo W. B. 
Published: June 2005

SummarySjögren‐Larsson syndrome (SLS) is an autosomal recessive disorder associated with reduced activity of the fatty alcohol: NAD+ oxidoreductase complex (FAO). Recent studies indicate that SLS patients are specifically deficient in the fatty aldehyde dehydrogenase (FALDH) component of FAO. To investigate the possibility of carrier detection for SLS, FAO and FALDH activities were measured in cultured skin fibroblasts from normal controls, obligate SLS heterozygotes, and SLS homozygotes using the 18‐carbon substrates octadecanol and octadecanal. Three of 11 heterozygotes for SLS had FAO activities that were within the normal range; the other 8 SLS heterozygotes had FAO activities below normal. In contrast, fibroblast FALDH activity was more effective than FAO in discriminating SLS heterozygotes from normal controls. FALDH activity (nmol min−1 (mg protein)−1) in normal controls was 8.54 ± 1.16 (mean ± SD; range 6.95–10.77;n=12) and in SLS heterozygotes was 5.12 ± 1.31 (range 3.28–6.96;n=11), or 60 ± 15% of mean normal activity. One SLS heterozygote had an FALDH activity within the lower range of normal; this heterozygote had an FAO activity below normal. None of the SLS heterozygotes had an FAO or FALDH activity that was in the range of that measured in SLS homozygotes. These results indicate that measurement of FAO and FALDH activities in cultured skin fibroblasts using 18‐carbon substrates is useful for SLS carrier detection.
Comparison of total cellular DNA, mRNA, and rRNA levels between normals and down syndrome patients
Authors: McQuillan C. I. , Choo K. H. 
Published: June 2005

SummaryTwo recent studies have suggested that the absolute cellular RNA and/or DNA levels in Down syndrome (DS) may be unusual compared to normals and may be linked to phenotypic expression (Pashet al., 1990; Dahlet al. 1988). We have extended these two studies by directly quantitating and comparing the total cellular mRNA, rRNA, and DNA levels in fibroblasts and lymphocytes derived from normal and DS individuals. The assay methods used, which allowed us to present the various nucleic acids levels in picograms per cell, did not reveal any significant difference between the two groups.
Leucine and tissue distribution of bulky and small neutral amino acids in rats: Dissociation between transport and insulin‐mediated effects
Authors: de Céspedes C. , Thoene J. G. , Lowler K. , Christensen H. N. 
Published: June 2005

SummaryThe mechanism of the observed decrease in the plasma concentration of several amino acids in the presence of high levels of Leu has remained unexplained. In the present study a decrease in the plasma concentration of Ile, Val, Phe, Tyr, Met, Ala, Pro and Gly was observed after the intraperitoneal injection of Leu to weanling rats. Decreases in net intracellular concentrations in muscle accompanied the decrease in plasma of all of these amino acids except Pro and Gly. An increase in the distribution ratio muscle/plasma was observed exclusively for Gly after administration of Leu or of a non‐insulinogenic transport system L analogue. Diazoxide suppressed the Leu‐induced decreases in plasma and muscle intracellular concentrations of Ile and Val as well as of Pro in plasma. An increase in the distribution ratio liver/plasma was observed for Pro and Gly in the absence but not in the presence of diazoxide. All the above changes were statistically significant. Hence insulin probably mediates Leu effects, promoting an increased utilization of Ile and Val in muscle and of Pro in liver. A more direct effect of Leu appears to be involved in the apparent increased utilization of Phe, Tyr and Ala in the same tissue. Gly depletion in plasma can be explained by its trapping by inhibitory action of Leu on the exodus of Gly through transport system L.
Alterations of NAD and adenylyl dinucleotide metabolism in Chediak‐Higashi Syndrome fibroblasts
Authors: Baker J. C. , Ames B. N. 
Published: June 2005

SummaryChediak‐Higashi syndrome (CHS) cells have been previously observed to exhibit several of the same characteristics as those of xeroderma pigmentosum (XP) and xeroderma pigmentosum variants. Cultured CHS fibroblasts have been examined for altered responses in both depletion of NAD and elevation of diadenosine‐5′,5‴‐tetraphosphate (Ap4A) following DNA damage since both responses have been reported as altered in XP cells and since Ap4A has been reported as absent from the platelets of CHS patients. Lowering of NAD following UV irradiation occurred in CHS cells in a manner similar to that of control and XP variant cells, but different from that of XP cells. CHS fibroblasts were not found to be deficient in Ap4A and exhibit basal levels very similar to those of control fibroblasts. No change in Ap4A pools were observed which correlated with cell growth, in contrast to previously published reports. Furthermore, while Ap4A levels are not elevated in XP cells, we observe an elevation of Ap4A pools in CHS cells which mimics the elevations observed in control and XP variant cells. We conclude that:

CHS cells more closely resemble control or XP variant cells than XP cells with regard to NAD lowering and Ap4A elevation following UV irradiation;

the photosensitivity exhibited by CHS cells is not due to general defects in the synthesis of poly(ADP‐ribose) from NAD or in Ap4A metabolism; and

alteration of Ap4A pool size in CHS fibroblasts is inappropriate as a biochemical marker for CHS.
Homocitrullinuria and homoargininuria in hyperargininaemia
Authors: Kato T. , Sano M. , Mizutani N. , Hayakawa C. 
Published: June 2005

SummaryA four‐year‐old boy with hyperargininaemia had increased urinary excretion of homocitrulline and homoarginine. A single oral lysine load created a marked increase in these amino acids in plasma. A daily oral lysine supplementation resulted in a remarkable urinary leakage of homocitrulline and homoarginine. These findings suggest that the patient had an enhanced synthesis of these amino acids.
Prolinase activity in prolidase‐deficient fibroblasts
Authors: Miech G. , Myara I. , Mangeot M. , Voigtlander V. , Lemonnier A. 
Published: June 2005

SummaryThe activity of prolinase (EC 3.4.13.8) was studied in cultured skin fibroblasts derived from three patients with deficient prolidase (EC 3.4.13.9). With pro‐val as substrate and manganese in the reaction buffer, prolinase activity was higher in prolidase‐deficient cells than in control cells (mean (SEM) 917 (67) nmol min−1 mg−1,n=3, control mean (SEM) 294, (50), n=11). The Michaelis constants were not different for the pro‐val and progly substrates in control and prolidase deficient fibroblasts. However, the constants for Vmax rose for both substrates in deficient cells. These results demonstrate that prolinase activity increases in prolidase‐deficient fibroblasts as also shown in the plasma of patients with prolidase deficiency. We suggest that in prolidase‐deficient fibroblasts, this rise in prolinase activity constitutes an attempt to compensate for the prolidase deficiency by increasing the greatly reduced intracellular proline pool.
Biotin‐responsive multiple carboxylase deficiency in an 8‐year‐old boy with normal serum biotinidase and fibroblast holocarboxylase‐synthetase activities
Authors: Holme E. , Jacobson C‐E. , Kristiansson B. 
Published: June 2005

SummaryAn 8‐year‐old boy with late onset multiple carboxylase deficiency is described. Biotinidase deficiency and holocarboxylase‐synthetase deficiency have been excluded. A very slow biochemical response to biotin was found. The decrease in urinary organic acid excretion followed first‐order kinetics with a half‐life of about 50 days. The initially low carboxylase activities in thrombocytes were increased but not normalized after 3 months of treatment.
The effect of oral betaine on vertebral body bone density in pyridoxine‐non‐responsive homocystinuria
Authors: Gahl W. A. , Bernardini I. , Chen S. , Kurtz D. , Horvath K. 
Published: June 2005

SummaryFive pyridoxine‐non‐responsive homocystinuric patients aged 5 to 32 years were treated with oral betaine, 3 g b.i.d, in a double‐blind, placebo‐controlled, two‐year crossover study of its effect on bone mineralization. Betaine therapy significantly reduced mean plasma homocystine (36±9 (SEM) µmol L−1 to 9±4 µmol L−1), with variable increases in plasma methionine and no adverse effects. Bone density, measured by computerized tomographic scanning of vertebral bodies, was below normal in all patients at the start of the study, and was not significantly altered by betaine therapy administered according to this protocol
α‐N‐acetylgalactosaminidase deficiency, a new lysosomal storage disorder
Authors: van Diggelen O. P. , Schindler D. , Willemsen R. , Boer M. , Kleijer W. J. , Huijmans J. G. M. , Blom W. , Galjaard H. 
Published: June 2005

SummaryA new lysosomal storage disease with autosomal recessive inheritance is described in two male siblings of 5 1/2 and 4 years of age. Clinical manifestations started after 9 months of age with neurological symptoms, followed by progressive psychomotor deterioration. Urinary oligosaccharide excretion was abnormal and showed a characteristic pattern on chromatography. Enzyme assays showed a profound deficiency of lysosomal α‐N‐acetylgalactosaminidase in cultured fibroblasts, leukocytes and plasma from the patients and reduced activity in material from the parents. The defiiciency was demonstrated both with an artificial substrate and a natural one, the blood group A trisaccharide. Excessive intra‐lysosomal storage of α‐N‐acetylgalactosamine‐containing material was demonstrated in cultured fibroblasts from the patients, using the lectin fromHelix pomatia which is specific for terminal α‐N‐acetylgalactosamine residues.
A protocol for the successful long‐term enzyme replacement therapy of scurvy in guinea pigs
Authors: Hadley K. , Sato P. 
Published: June 2005

SummaryGulonolactone oxidase, a key enzyme in the biosynthesis of ascorbic acid, is missing from guinea pigs and certain other scurvy‐prone species. Weekly intraperitoneal injections of glutaraldehyde cross‐linked immunoprecipitates of this enzyme have been shown to provide guinea pigs with the capability of synthesizing their own ascorbic acid and of surviving without an exogenous source of this vitamin. This protocol, however, was successful in only a small percentage of the animals tested. The reasons for the limited therapeutic success were investigated. Apparently, the gulonolactone oxidase‐treated guinea pigs fed without ascorbic acid were receiving insufficient nutrition. By supplementing these enzyme‐treated animals with vitamins A, B, D and E and selenium, we successfully maintained a high proportion of guinea pigs fed without vitamin C.
Developmental profile of patients with maple syrup urine disease
Authors: Nord A. , van Doorninck W. J. , Greene C. 
Published: June 2005

SummaryThe progress of nine maple syrup urine disease patients (eight classical, one possible variant) was reviewed to look for similarities in developmental patterns. A consistent developmental profile of stronger Verbal than Performance IQ and lower than familially expected IQ was seen. Younger age at diagnosis was associated with a milder neonatal course. Those who were asymptomatic or suffered mild complications in the newborn period have higher IQs than children experiencing moderate or severe complications. Children with asymptomatic or mild neonatal course also required less special education services. Overall, a picture of ubiquitous motor, visual‐analytic and learning deficits is seen.
Bony changes of PKU neonates unrelated to phenylalanine levels
Authors: Fisch R. O. , Feinberg S. B. , Weisberg S. , Day D. 
Published: June 2005

SummaryIn 1962 bone abnormalities were described radiographically in phenylketonuria patients. Later, observations were made on PKU infants during the neonatal period, which allowed differentiation between inherited alterations in bone development from those changes due to dietary restriction. Similar changes have been described in other aminoacidurias. Wrist radiographs and serum phenylalanine levels were obtained on 73 patients first seen between 1965 and 1990. All radiographs were taken on the day of referral, when the patient was between 6 and 57 days old. Forty‐nine patients were less than 28 days old. Bone abnormalities were present in 56 of 73 (77%) of the children, as compared to 0 of 16 in a control group. The presence or absence of bone abnormality is unrelated to serum phenylalanine level, and to the age of the children at referral. This finding suggests that the cause of these mesodermal changes is not a deviation of a single amino acid in the infant, but that they are caused by an intrauterine amino acid imbalance.
Familial combined hyperlipidaemia: Use of stable isotopes to demonstrate overproduction of very low‐density lipoprotein apolipoprotein B by the liver
Authors: Cortner J. A. , Coates P. M. , Bennett M. J. , Cryer D. R. , Le Ngoc‐Anh 
Published: June 2005

SummaryWe have assessed very low‐density lipoprotein apolipoprotein B production, using [15N]glycine as an endogenous marker in a 9‐hour primed constant infusion protocol, in four adult male subjects with familial combined hyperlipidaemia and in four normolipidaemic adult male controls. The mean very low‐density lipoprotein apolipoprotein B absolute synthetic rate was significantly greater in the familial combined hyperlipidaemic subjects than in control subjects (26.31 ± 8.37 vs 9.36 ± 4.07 mg/kg per 24 h,p<0.05). These results confirm findings using exogenous radioisotope labelling techniques that very low‐density lipoprotein apolipoprotein B production is significantly increased in most patients with familial combined hyperlipidaemia. A modified 9‐hour protocol can be safely done repeatedly and in children and pregnant women.
Peroxisomes in infantile phytanic acid storage disease: a cytochemical study of skin fibroblasts
Authors: Beard M. E. , Moser A. B. , Sapirstein V. , Holtzman E. 
Published: June 2005

AbstractCultured skin fibroblasts from six patients demonstrating clinical signs and biochemical characteristics of infantile phytanic acid storage disease (IPSD) were examined by electron microscopy, using cytochemical procedures for the demonstration of peroxisomal catalase activity. In four of the six fibroblast cell lines peroxisomes strongly reactive for catalase were present in numbers similar to those found in normal fibroblasts. Liver biopsy tissue from one of these patients showed no typical hepatic peroxisomes, but did show small, marginally reactive bodies. In two other IPSD fibroblast cell lines peroxisomes with appreciable cytochemical reactivity were rare or absent. It seems, therefore, that infantile phytanic acid storage disease is heterogeneous with respect to the presence of cytochemically recognizable peroxisomes, at least in the cases studied here. Furthermore, peroxisomes may be markedly affected in one cell type — liver — and yet not affected in another — skin fibroblasts — within a single individual.
A new variant of sphingomyelinase deficiency (Niemann‐Pick): visceromegaly, minimal neurological lesions and lowin vivo degradation rate of sphingomyelin
Authors: Elleder M. , Nevoral J. , Špičáková V. , Hyniová H. , Kraus J. , Krásný J. , Vanier M. T. 
Published: June 2005

AbstractThree males (aged 10 years, 3 years 9 months and 2 years 8 months) with profound sphingomyelinase deficiency are presented. The sphingomyelin storage in the liver biopsies attained 30‐fold, 65‐fold and 16‐fold increases against controls, respectively. Levels of bis(monoacylglyceryl) phosphate were also increased. In two cases the bone marrow contained foam cells with liquid crystals of sphingomyelin. Besides the visceral involvement dominated by hepatosplenomegaly, all three cases showed discrete, so far stationary (8 years, 42 months and 28 months) neuropathic features and retinal lesions resembling the classical cherry‐red spot. Electrophysiological examinations showed a variable reduction of peripheral nerve conduction velocity and prolongation of the latencies of somatosensory, visual and auditory evoked potentials. Ultrastructural examination of skin nerves showed a slight storage, mainly in Schwann cells. In some myelinated fibres there were pseudomyelinic ovoids. The cases therefore displayed features of both A and B types of sphingomyelinase deficiency and should be conventionally classified as intermediate. However, the very low levels ofin vivo sphingomyelin hydrolysis (not exceeding 6%, against 30±10% in type B and 77±5% in controls) were clearly within the range of type A values (5±2%). Accordingly, we suggest that the cases may be biochemically classified as variants of type A disease.
Immunological evidence for a carbamylphosphate synthetase lesion resulting in the formation of enzyme with altered sub‐unit size
Authors: Hoogenraad N. J. , Weston H. J. , Mackenzie N. 
Published: June 2005

AbstractA partial carbamylphosphate synthetase (CPS: EC 6.3.4.16) deficiency (McKusick 23730) was found in a male child who presented with generalized convulsions, rickets and apnoeic attacks at six months of age. By his second year he showed serious developmental delay and a gut biopsy revealed an absence of CPS activity with an elevated ornithine transcarbamylase activity. Analysis of the gut biopsy sample on SDS‐polyacrylamide gels, followed by electrophoretic transfer to a nitrocellulose filter probed with monospecific antibodies to CPS showed that the child had normal levels of immunoreactive enzyme, but instead of one band corresponding to normal CPS with a subunit size of 165 000u, the patient had three immunoreactive bands, one larger and two smaller than that found in normal controls. The genetic defect in this child therefore results in an unusual form of CPS being made which has markedly reduced enzyme activity.
Glycerol‐3‐phosphate excretion in fructose‐1,6‐diphosphatase deficiency
Authors: Krywawych S. , Katz G. , Lawson A. M. , Wyatt S. , Brenton D. P. 
Published: June 2005

AbstractA patient aged 23 months with fructose‐1,6‐diphosphatase deficiency is reported. This infant demonstrated an increased urine excretion of glycerol‐3‐phosphate during episodes of hypoglycaemia. The excretion of this compound has not previously been described in this disease or in those disorders associated with a deficiency in one of the other three gluconeogenic enzymes associated with hypoglycaemia. Its presence in the urine from patients may be useful in diagnosis.
A new case of arginase deficiency in a Spanish male
Authors: Jordá A. , Rubio V. , Portolés M. , Vilas J. , García‐Piño J. 
Published: June 2005

AbstractA new case of arginase deficiency is reported in a male newborn from Spain. In contrast with the majority of the earlier cases, this infant showed severe protein intolerance of early onset. The diagnosis was based on the assay of the urea cycle enzymes in a postmortem liver sample. Levels of erythrocyte arginase were also determined in the parents and in a sister of the patient, and were consistent with heterozygosity. From a study of the pedigree it appears that arginase deficiency in this family presents a dramatic course.
A neonatal screening approach to the detection of familial hypercholesterolaemia and family‐based coronary prevention
Authors: Wilcken D. E. L. , Blades B. L. , Dudman N. P. B. 
Published: June 2005

SummaryWe measured by radial immunodiffusion apolipoprotein B (ApoB) as a genetic marker for familial hypercholesterolaemia in heel prick blood spot samples on filter paper routinely collected from 5000 3‐ to 5‐day‐old neonates for current screening programmes. Dried blood spot ApoB levels were distributed continuously and were 9% higher in female neonates than in males (0.246±0.085 versus 0.225±0.079 g/L of whole blood, mean ±SD,p<0.0001). Neonates of birth weight under 2.5 kg had lower levels than the population mean in both sexes but levels did not change with birth weight within this range; in those with the birth weights greater than 2.5 kg levels increased with increasing birth weight. Sex and birth weight could account for 5.7% of the variability of ApoB. Levels had largely stabilized by day 3 of life. Of parents of neonates whose ApoB levels were among the top 2%, 45 families were available for study when the infants were aged 12.3±3.3 months. In 6 of these families there was a persisting elevation of ApoB both in the infants (levels greater than 0.7 g/L of whole blood) and in one parent who also had elevated ApoB and a lipid profile of familial hypercholesterolaemia phenotype, results indicating an ascertainment rate of between 1 in 365 and 1 in 830 of the screened population. These studies have defined the variables affecting neonatal ApoB levels and establish that neonatal screening for familial hypercholesterolaemia is feasible. Primary prevention of vascular disease in young families with the gene should be possible with this approach.