bluuebunny/crossref_metadata_2025_split huggingface dataset:
Further analysis of the disturbed adrenocortical function in the cerebro‐hepato‐renal syndrome of zellweger
Authors: Govaerts L. , Sippell W. G. , Monnens L. 
Published: June 2005

SummaryPlasma aldosterone, corticosterone, 11‐deoxycorticosterone, progesterone, 17‐hydroxyprogesterone, 11‐desoxycortisol, cortisol and cortisone were determined simultaneously in small plasma samples obtained during an i.v. ACTH (Synacthen) stimulation test in five patients (age 4–7 years) with Zellweger syndrome. The response of all ACTH‐dependent steroids to Synacthen was severely impaired in all patients, despite normal basal levels. It can be concluded that the biochemical defect in adrenal steroidogenesis causing the inadequate response to ACTH injection is located proximal to progesterone.We propose that the lack of responsiveness to ACTH is secondary to an abnormality of ACTH receptors on the adrenocortical cell. The extremely low levels of non‐specific lipid transfer protein may be a contributing factor.
Myoclonic epilepsy of lafora and arylsulphatase a deficiency in the same patient
Authors: Bertagnolio B. , Girotti F. , Pelucchetti D. , Pandolfo M. 
Published: June 2005

SummaryVery low levels of arylsulphatase A were found in a young patient with the clinical features of Lafora disease, confirmed by muscle biopsy. The deficiency was shown both in leukocytes and cultured fibroblasts. A cerebroside sulphate loading showed that 93% of [14C]cerebroside sulphate taken up by skin fibroblasts from the patient remained unmetabolized after a 24 h pulse, ruling out pseudo‐arylsulphatase A deficiency. In the healthy parents and siblings of the patient, biochemical data suggested heterozygosity for arylsulphatase A deficiency. The apparent co‐inheritance of arylsulphatase A deficiency and Lafora disease in this family might be the consequence of genetic linkage between the two genes.
Sanfilippo B disease: a re‐examination of a particular sibship after 12 years
Authors: Di Natale P. 
Published: June 2005

SummaryA particular sibship, with mild and severe types of Sanfilippo B disease within the same family, was re‐examined after 12 years. The phenotypes of the mild and of the severe patients were maintained, specifically the mental retardation. Cultures of lymphoblasts from the mild patient were established and proteins were electrophoresed in native conditions and then immunoblotted with specific antibody. Two bands of 182000 and 131000 Da were found, comigrating with the enzyme from normal lymphoblasts and the enzyme from normal urine. The data are discussed in relationship to the molecular defect underlyingα‐N‐acetylglucosaminidase deficiency and to the ability of the antiserum to react with normal, mutant, monomeric and multimeric forms of the enzyme.
Successful treatment of dihydropteridine reductase deficiency, with an interesting effect of 5‐hydroxytryptophan deficiency on sleep patterns
Authors: Lipson A. H. , Earl J. W. , Wilcken B. , Yu J. S. , O'Halloran M. , Cotton R. G. H. 
Published: June 2005

SummaryWe report a child in whom dihydropteridine reductase deficiency was diagnosed prenatally because of an affected sibling and who was treated from birth with apparent good response.This family has been reported before (Firgairaet al., 1980, 1981, 1983; Lipsonet al., 1984; Cottonet al., 1986; Dahlet al., 1988). The parents are Lebanese Muslims who are first cousins, and their first and third children, both male, are well. The third child was diagnosed as normalin utero (Firgairaet al., 1983). The second child, the subject of an early report (Lipsonet al., 1984), has dihydropteridine reductase deficiency. The dihydropteridine reductase is non‐functional due to an amino acid insertion (Howellset al., 1990).
Urinary excretion of 2‐methylacetoacetate, 2‐methyl‐3‐hydroxybutyrate and tiglylglycine after isoleucine loading in the diagnosis of 2‐methylacetoacetyl‐CoA thiolase deficiency
Authors: Aramaki S. , Lehotay D. , Sweetman L. , Nyhan W. L. , Winter S. C. , Middleton B. 
Published: June 2005

SummaryThe concentrations of 2‐methylacetoacetate, 2‐methyl‐3‐hydroxybutyrate and tiglylglycine were determined by gas chromatography‐mass spectrometry in urine collected before and for 8 h after loading with 100mg of isoleucine per kg of body weight. The sum of 2‐methylacetoacetate and 2‐butanone, a decarboxylation product, was determined as the 2‐butanone dinitrophenylhydrazone derivative. Substantial increases in each compound were encountered in a patient with a documented defect of 2‐methylacetoacetyl‐CoA thiolase. Increased quantities of 2‐methyl‐3‐hydroxybutyrate and tiglylglycine were also found in four children with clinical symptoms similar to those associated with 2‐methylacetoacetyl‐CoA thiolase deficiency but in whom the activity of the enzyme was found to be normal. The concentration of 2‐methylacetoacetate plus 2‐butanone in the urine increased after an isoleucine load only in the patient with 2‐methylacetoacetyl‐CoA thiolase deficiency.
Biochemical observations on a case of hepatic fructose‐1,6‐diphosphatase deficiency
Authors: Hommes F. A. , Campbell R. , Steinhart C. , Roesel R. A. , Bowyer F. 
Published: June 2005

AbstractA case of hepatic fructose‐1,6‐diphosphatase deficiency is described. She presented with congenital bilateral cataracts, failure to thrive, hypoglycaemia and hyperlactacidaemia. A liver biopsy revealed normal levels of gluconeogenic enzymes except fructose‐1,6‐diphosphatase which was present at 30% of the level of the lower control values. The residual activity had a normal affinity for fructose‐1,6‐diphosphate, a decreased sensitivity for inhibition by fructose‐2,6‐diphosphate and an increased resistance toward conversion to the AMP‐insensitive form of the enzyme. As a result of this mutation, the residual FDPase will always be maintained in the AMP‐inhibited form.
Dolichol and phosphorylated dolichol content of tissues in ceroid‐lipofuscinosis
Authors: Hall N. A. , Patrick A. D. 
Published: June 2005

AbstractConcentrations of free dolichol, total non‐phosphorylated dolichol, and total phosphorylated dolichol were measured in autopsy specimens of brain and liver from ceroid‐lipofuscinosis (CL) and control cases. Levels of non‐phosphorylated dolichol, mainly as free dolichol, were increased approximately two‐fold in late‐infantile CL brain. No increase was observed for CL liver. In late‐infantile and juvenile CL brain, the increase in phosphorylated dolichol was at least ten‐fold, but no significant difference was found for CL liver. A substantial part of the increase in phosphorylated dolichol in CL brain appeared to be due to lipid‐linked oligosaccharides. The results suggest that CL might involve a defect in the metabolism of dolichol‐linked oligosaccharides.
Intracellular activity of HPRTCape Town: Purine uptake and growth of cultured cells in selective media
Authors: Steyn L. M. , Harley E. H. 
Published: June 2005

AbstractThe low activity of the human variant HPRTCape Town is associated with substrate inhibition by hypoxanthine and guaninein vitro. The intracellular activity of this variant was investigated by studying the relative uptake or radiolabelled purine nucleotide precursors and the growth in selective media of EBvirus‐transformed lymphoblasts prepared from the proband (TK). These cells incorporated less than 10% of the [14C]hypoxanthine and [14C]guanine of the control cells; while their purinede novo synthesis was accelerated 8‐fold. In selective media the HPRTCapeTown cells grew in a similar manner to HPRT‐ve cells. These results indicate that if substrate inhibition is responsible for the low intracellular activity of HPRTCape Town, the concentration of either hypoxanthine or guanine in the vicinity of the active site of the enzyme must be greater than theKi(app) for these substrates, 118 and 28 µmol L−1 respectively. Evidence is presented that the intracellular concentration of guanine, but not hypoxanthine, is well in excess of theKi(app) in cultured lymphoblasts.
Successful adjustment to society by adults with phenylketonuria
Authors: Koch R. , Yusin M. , Fishler K. 
Published: June 2005

AbstractThe study shows that most individuals between 16 and 25 years of age with PKU appear to function in a productive manner in society. Although they have not become professional men and women, they can acquire jobs of a skilled or semiskilled nature and perform them satisfactorily. The majority seemed content with their jobs and happy with the way their lives were progressing, although only 23% were financially independent. Of the patients interviewed, the majority had made friendships and appeared to keep them without much trouble. The majority of the patients would not tell their friends that they had PKU. The reason for this was that they felt uncomfortable acknowledging that they had this disorder.
Cystinosis in the Federal Republic of Germany. Coordination and analysis of the data
Authors: Manz F. , Gretz N. 
Published: June 2005

AbstractIn our survey, 101 infants and children with cystinosis were registered in the Federal Republic of Germany. Ninety‐five patients showed the infantile type of cystinosis, five the adolescent type and one possibly the adult type. The minimum incidence rate of infantile and adolescent cystinosis in the FRG was 1 patient per 179 000 live‐births. In contrast to other countries, cystinotic patients were evenly distributed in the FRG. Patients with cystinosis originated more frequently from rural communities than from large cities. Before 1968 most patients died before reaching terminal renal failure, usually due to uncontrolled disturbances of water and electrolyte metabolism. Since 1976 the causes of death other than uraemia have been rare and most patients with terminal renal failure have entered a renal replacement program.
Disturbed very long chain (C24–C26) fatty acid pattern in fibroblasts of patients with Zellweger's syndrome
Authors: Govaerts L. , Bakkeren J. , Monnens L. , Maas J. , Trijbels F. , Kleijer W. 
Published: June 2005

AbstractThe very long chain fatty acids in cultured fibroblasts from six patients with the cerebro‐hepato‐renal syndrome of Zellweger, from six of their parents, from three controls, and also in three amniotic fluid control cell lines were analysed by gas chromatography. Increased concentrations of hexacosanoic acid (C26:O) were consistently found in the Zellweger syndrome. Also the ratios C26:O/C22:O, C25:O/C22:O, and C24:O/C22:O were elevated. The very long chain fatty acid levels and ratios in fibroblasts from the patients' parents were within the normal range. Findings in amniotic fluid cell lines indicate the possibility of antenatal diagnosis for Zellweger's syndrome. The similarities between neonatal adrenoleukodystrophy and Zellweger's syndrome suggest the applicability of this technique also in neonatal adrenoleukodystrophy.
Inability of second trimester human amniotic fluid cell cultures to aromatize C19‐steroids
Authors: O'Shannessy D. J. , Renwick A. G. C. 
Published: June 2005

AbstractAmniotic fluid (AF) and fibroblast (F) cell types, derived from human amniotic fluid by amniocentesis in the second trimester, were cultured using media of varying composition and their ability to transform C19‐steroids to oestrogens was investigated by fluorimetry, radioimmunoassay, tritium release and measurement of cytochrome P450. Although the cells were shown to be metabolically active by the presence of mitotic figures, the incorporation of tritiated leucine into protein and the production of the β‐subunit of hCG, no evidence of aromatization was obtained despite the inclusion in the medium of a number of steroids known to be transformed to oestrogens in severalin vivo andin vitro preparations. The addition of reported stimulants of aromatase activity, viz. hCG, FSH, diethylstilbestrol, prostaglandins E2 and F2α and dibutyryl cyclic AMP, was without effect.
Gaucher disease (type 1): Physical and kinetic properties of liposomal and soluble ‘acid’ β‐glucosidase
Authors: Carroll M. 
Published: June 2005

Abstract‘Acid’ β‐glucosidase of human spleen, from either normal controls or patients with type 1 (adult) Gaucher disease, was incorporated into phosphatidylcholine liposomes. The non‐incorporated (soluble) Gaucherenzyme had a higher apparent molecular weight than had the corresponding control. Liposomal ‘acid’ β‐glucosidase prepared from Gaucher‐spleen was more thermostable than was the corresponding normal enzyme; it was also stimulated by acidic lipids to a much lesser extent. The results suggest that the genetic mutation in type 1 (adult) Gaucher disease has multiple effects on the glycoprotein form of ‘acid’ β‐glucosidase.
Comparison of ornithine metabolism in hyperornithinaemia‐hyperammonaemia‐homocitrullinuria syndrome, lysinuric protein intolerance and gyrate atrophy fibroblasts
Authors: Botschner J. , Smith D. W. , Simell O. , Scriver C. R. 
Published: June 2005

SummaryWe measuredl‐ornithine oxidation in cultured skin fibroblasts from seven patients with hyperornithinaemia‐hyperammonaemia‐homocitrullinuria (HHH) syndrome (McKusick 23897), and compared it with oxidation by ornithine aminotransferase deficient gyrate atrophy (McKusick 25887) cells and lysinuric protein intolerance (McKusick 22270) cells in which there is an ornithine transport abnormality at the plasma membrane. Net uptake of ornithine is not abnormal in intact HHH cells. Ornithine oxidation was depressed in HHH and gyrate atrophy cells but not in lysinuric protein intolerance cells; the latter finding suggests there is no significant mitochondrial defect in lysinuric protein intolerance cells. Since HHH cells have intact ornithine aminotransferase, impaired oxidation is compatible with deficient penetration of ornithine into mitochondria in this disease. We could not demonstrate a gene dosage effect in oxidation values.
The role of the blood‐brain barrier in the aetiology of permanent brain dysfunction in hyperphenylalaninaemia
Authors: Hommes F. A. 
Published: June 2005

SummaryCalculations on the rate of entry of the neutral amino acids into the brain via the blood‐brain barrier show that a considerable decrease in this rate, particularly for tryptophan and tyrosine, takes place in histidinaemia and tyrosinaemia, type II. These conditions are, however, not associated with mental retardation. It is therefore concluded that effects at the blood‐brain barrier alone do not provide an adequate explanation for the aetiology of permanent brain dysfunction in hyperphenylalaninaemia.
Abnormal fatty acid composition of biotin‐responsive multiple carboxylase deficiency fibroblasts
Authors: Packman S. , Whitney S. C. , Fitch M. , Fleming S. E. 
Published: June 2005

SummaryClinical and biochemical correlations in the biotin‐responsive multiple carboxylase deficiencies have suggested that disordered lipogenesis plays a role in the pathogenesis of the disease. In particular, the activity of biotin‐dependent acetyl CoA carboxylase and thede novo synthesis of fatty acids are reduced in mutant fibroblasts. In the present work, we examine the biochemical consequences of these deficiencies, and document and characterize an abnormal fatty acid composition in holocarboxylase synthetase deficiency fibroblasts. Following growth in biotin‐restricted medium, the total fatty acid content of mutant cells is reduced. There were significant reductions in the percentage as 16:0, 18:0 and 20:3N9 fatty acids, with the proportion of longer‐chain fatty acids either increased or maintained at control levels. The cellular content of 16:0, 16:1, 18:0, 18:1 and 20:3N9 fatty acids was reduced, while that of the longer‐chain fatty acids was preserved at control levels in mutant cells deprived of biotin. We speculate that the components of the altered fatty acid pools may be disproportionately incorporated into complex lipids in mutant cells, with pathologic effects on the multiple carboxylase deficiency phenotype.
Cultured skin fibroblasts: Useful for diagnosis of Wilson's disease?
Authors: Van den Berg G. J. , Van den Hamer C. J. A. , Meijer R. J. , Hoogenraad T. U. 
Published: June 2005

SummaryThe copper content of and radiocopper uptake in fibroblast cultures were studied to evaluate their usefulness for the diagnosis of Wilson's disease. We used methods closely related to those described in the literature, and applied these to cell lines of six patients with Wilson's disease and 12 controls. The results were:

The copper content of the cytosol of skin fibroblasts derived from patients with Wilson's disease was lower than that of controls when the cells were grown in a medium with a low copper concentration (0.7 µmol L−1); increased copper concentration (157 µmol L−1 in the medium failed to demonstrate any difference between normal fibroblasts and those derived from patients with Wilson's disease.

Radiocopper uptake studies did not differentiate between normal fibroblasts and fibroblasts from patients with Wilson's disease.
We conclude that the cytosolic copper content of fibroblasts grown in a low copper medium is a potential diagnostic tool in Wilson's disease. At present not all controls can be distinguished from the Wilson cells; ways must be sought, therefore, of improving the technique.
Excretion of hippuric acid during sodium benzoate therapy in patients with hyperglycinaemia or hyperammonaemia
Authors: Barshop B. A. , Breuer J. , Holm J. , Leslie J. , Nyhan W. L. 
Published: June 2005

SummaryIn patients with non‐ketotic hyperglycinaemia and two patients with urea cycle disorders treated with varying doses of sodium benzoate there was a linear correlation between intake of benzoate and excretion of hippurate. Patients with non‐ketotic hyperglycinaemia excreted significantly more benzoate in the form of hippurate than patients with urea cycle disorders (74 ± 7.0vs 41 ± 3.6%). The plasma concentration of glycine decreased following benzoate treatment only in the patients with non‐ketotic hyperglycinaemia. The observed difference between the two groups in the excretion of hippurate seems to support the concept that glycine availability may be limiting in benzoate therapy for some patients.
Glutathionuria: γ‐Glutamyl transpeptidase deficiency
Authors: Wright Elaine C. , Stern J. , Ersser R. , Patrick A. D. 
Published: June 2005

AbstractA mentally retarded young woman with severe behaviour problems was found to excrete large amounts of glutathione due to a generalized γ‐glutamyl transpeptidase deficiency. As in the only other case described in detail, plasma levels and renal reabsorption of the amino acids were normal. In the parents' urine, plasma and leukocytes, enzyme activity was normal but in their cultured fibroblasts it was below the minimum for the control range. An autosomal recessive mode of inheritance is suggested. The implications of these findings for the possible role of the γ‐glutamyl cycle in amino acid transport are briefly discussed.
Leigh's disease with decreased activities of pyruvate carboxylase and pyruvate decarboxylase
Authors: Van Biervliet J. P. G. M. , Duran M. , Wadman S. K. , Koster J. F. , van Rossum A. 
Published: June 2005

AbstractIn a patient with the clinical symptoms of Leigh's disease a partial deficiency of hepatic pyruvate carboxylase and pyruvate decarboxylase was found at necropsy. Cerebral pyruvate decarboxylase activity was also diminished. All enzyme activities were measured in total homogenates. The finding of typical necrotic lesions in the brain stem was consistent with the clinical diagnosis. During life moderate lactic acidaemia and no hypoglycaemia were observed, but an abnormal organic acid excretion pattern was present. The contribution of the enzyme defects to the aetiology of the disease is discussed.
Myelin and its abnormalities
Authors: McKhann G. M. , Poduslo S. E. 
Published: June 2005

AbstractThis review starts with a brief outline about what myelin is, what it does, and how it is formed. Attention is then turned to newer methods of studying myelinationin vitro. Finally, diseases which can affect myelin are commented upon and advances which have occurred over the last few years are pointed out.
Failure of protein loading tests to identify heterozygosity for ornithine carbamoyltransferase deficiency
Authors: Becroft D. M. O. , Barry D. M. J. , Webster D. R. , Simmonds H. A. 
Published: June 2005

AbstractProtein loading tests for the diagnosis of heterozygous ornithine carbamoyltransferase deficiency were performed on two occasions on an asymptomatic woman whose daughter and two infant sons died of the disease. Neither loading test produced the expected increases in urinary orotic acid excretion and studies of other pyrimidine and purine metabolites in urine and plasma did not suggest that these would provide better discrimination from non‐carriers. The results probably reflect an extensive inactivation of the mutant X chromosome in liver cells and reinforce the need for caution in interpreting negative test results.
A treatment of non‐ketotic hyperglycinaemia
Authors: Schoos‐Barbette S. , Gerard J. , Francotte N. , Lambotte C. 
Published: June 2005

AbstractThe treatment comprising a special diet (without glycine, serine, and with a reduced amount of threonine), strychnine nitrate and ursodesoxycholic acid (UDCA) led to normoglycinaemia in this form of severe nonketotic glycine encephalopathy. Diet and treatment were well tolerated but without significant effect upon psychomotor development. This treatment should be more effective if administered before irreversible brain damage occurs, particularly in moderate and chronic forms of NKH.
Possible explanation for hyperglycinaemia in propionic acidaemia and methylmalonic acidaemia: Propionate and methylmalonate inhibit liver and brain mitochondrial glycine transport
Authors: Ugarte M. , Lopez‐Lahoya J. , Garcia M. L. , Benavides J. , Valdivieso F. 
Published: June 2005

AbstractThe effect of propionate and methylmalonate on the transport of glycine into rat liver and brain mitochondria was investigated. Both propionate and methylmalonate markedly inhibited mitochondrial glycine transport. These compounds also inhibited14CO2 production from [14C]glycine by isolated brain and liver mitochondria and glycine metabolism in rat brain cortex slices. These results are discussed with reference to hyperglycinaemia associated with propionic acidaemia and methylmalonic acidaemia and as a possible contributory factor to the pathological mechanisms in these conditions.
Aspartylglycosaminuria in Northern Norway in eight patients: Clinical heterogeneity and variations with the diet
Authors: Borud O. , Strömme J. H. , Lie S. O. , Torp K. H. 
Published: June 2005

AbstractUrinary excretion of aspartylglycosamines was investigated in eight patients by semiquantitative thin‐layer chromatography, and bound glycosamines by a quantitative photometric method (Elson‐Morgan reaction). Each patient showed a fairly constant level, relative to the creatinine, of aspartylglycosamines in urine. The least retarded patient, aged 31, excreted about 350 mg/g creatinine, one‐third of that found in two severely retarded young patients, aged 4 and 7 years (1400 and 940 mg/g creatinine, respectively). Three days on a low‐protein diet did not change the aspartylglycosamine excretion in the patient showing the highest excretion rate.
Diagnosis of Gaucher's disease in cultured skin fibroblasts and leucocytes
Authors: Butterworth J. , Broadhead D. M. 
Published: June 2005

AbstractWashing skin fibroblasts or leucocytes in 0.25 mol/l sucrose increases the activity ofβ‐glucosidase at acid pH. This effect is primarily due to removal of low levels of sodium chloride, which inhibit acidβ‐glucosidase. A secondary factor for skin fibroblasts is the removal of residual phosphate buffer pH 7.3 used to wash the cells following trypsinization. As theβ‐glucosidase activity of water‐lysed leucocytes is higher at acid pH than that of a saline suspension of leucocytes, the former are better for the diagnosis of Gaucher's disease. However, more reliable results still may be obtained by assay of this enzyme in cultured skin fibroblasts.