bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cockayne syndrome: Magnetic resonance images of the brain in a severe form with early onset
Authors: Nishio H. , Kodama S. , Matsuo T. , Ichihashi M. , Ito H. , Fujiwara Y. 
Published: June 2005

SummaryA 2‐year‐old boy with an early onset and severe form of Cockayne's syndrome (CS) showed differences from the common CS form, which made the clinical diagnosis difficult. However, the cellular characteristics of CS, that the patient's skin fibroblasts exhibited the hypersensitivity to the lethal effect of 254 nm ultraviolet light (UV) and a defective recovery of post‐UV DNA synthesis, but normal level of UV‐induced unscheduled DNA synthesis, were observed. The magnetic resonance imaging (MRI) by the inversion‐recovery method of the brain at age of 26 months showed atrophy or poor development of high signal images of the white matter. The MRI spin‐echo image showed a low signal image of the lenticular nucleus. The T1 and T2 values of the cerebrum (grey matter, white matter, lenticular nucleus and thalamus) were greater than those of the age‐matched controls, but similar to infant brains with much free water. Such MRI findings may suggest hypomyelination leading to the severe atrophy of the brain in this CS patient. His severe symptoms progressed rapidly until his death at 35 months due to systemic sepsis and renal dysfunction. Autopsy revealed severe microcephaly, severe atrophy of cerebrum, cerebellum and brain stem, and calcification throughout the brain, especially in the basal ganglia. Myelin staining showed numerous patchy losses of myelination in the cortical white matter.
The effects of fetal energy depletion on amniotic fluid concentrations of amino acids, organic acids and related metabolites
Authors: Harkness R. A. , Purkiss P. , Duffy S. , Chalmers R. A. , Jones M. 
Published: June 2005

SummaryConcentrations of amino and organic acids, phosphate, sulphate, gluconic acid and gluconolactone were measured in amniotic fluid samples which contained either normal or raised hypoxanthine concentrations. In this way, the effect of mild fetal ATP depletion could be determined.The effects of this mild asphyxia were to raise concentrations of phenylalanine, tyrosine, lysine, glycine, phosphate, sulphate, gluconic acid and glucono‐1,5‐lactone. However, concentrations of a variety of other metabolites were unchanged; thus no diagnostic confusion should arise with organic acidurias in mild asphyxia in contrast to the biochemical mimickry produced by severe asphyxia. Since clinically normal parturition can produce changes in amniotic fluid, urine from newborn or cord blood may not reflect the metabolic balancein utero.
Deficiency of UMP synthase in dairy cattle: A model for hereditary orotic aciduria
Authors: Harden K. K. , Robinson J. L. 
Published: June 2005

SummaryDeficiency of uridine‐5′‐monophosphate (UMP) synthase in dairy cattle, a condition analogous to human hereditary orotic aciduria, is reviewed with consideration of similarities and differences between the enzyme deficiency in humans and cattle. New findings regarding the bovine condition are reported including presence of the enzyme deficiency in numerous tissues and absence of substantial effects on other aspects of nucleotide metabolism. Specifically, erythrocyte concentration of phosphoribosylpyrophosphate (PRPP) and activities of PRPP synthetase, adenine phosphoribosyltransferase, and hypoxanthine‐guanine phosphoribosyltransferase appear to be normal in cattle heterozygous for UMP synthase deficiency.
Studies on cross‐reacting material to steroid sulphatase in fibroblasts from patients affected by different types of steroid sulphatase deficiency
Authors: Parenti G. , Ballabio A. , Hoogeveen A. T. , Van Der Loos C. M. , Jobsis A. C. , Andria G. 
Published: June 2005

SummaryImmunologically cross‐reacting material to antibodies against steroid sulphatase has not been found in fibroblasts from patients with steroid sulphatase deficiency.
Successful long term therapy of biopterin deficiency
Authors: Snyderman S. E. , Sansaricq C. , Pulmones M. T. 
Published: June 2005

SummaryA hyperphenylalaninaemic infant, started on dietary therapy at 14 days of age, had severe developmental retardation and neurological abnormalities despite excellent biochemical control. A diagnosis of a deficit in biopterin synthesis was made at five months of age as a result of the following: high neopterin and low biopterin levels in both blood and urine, normal dihydropteridine reductase in the liver and a sharp drop in the plasma phenylalanine level 4 h after the administration of a test dose of tetrahydrobiopterin. Treatment with levodopa, carbidopa and 5‐hydroxytryptophan resulted in prompt neurological improvement. This was followed by gradual and sustained development. At present, at the age of 7 years, the child is mentally and physically normal.
Influence of the phenylketonuric heterozygote on the developing fetus
Authors: Cabalska B. , Miesowicz I. , Zorska K. , Nowaczewska I. , Duczynska N. 
Published: June 2005

AbstractPhysical development scores and clinical condition were evaluated in 403 newborn of phenylketonuric (PKU) heterozygotes. No significant differences were found between this group and the progeny of women from a healthy population. Analysis of mental development scores in 82 non‐PKU children age 3–14 years born to heterozygous mothers revealed normal values of psychometric tests.
Spectral studies of the interaction of the substrate ‘quinonoid’ 6‐methyl dihydropterine and the coenzyme NADH used as marker in the dihydropteridine reductase assay
Authors: van der Heiden C. , Brink W. 
Published: June 2005

AbstractIn dihydropteridine reductase assay the substrate quinonoid dihydropterine is reduced again to tetrahydropterine, concomitantly oxidizing NADH, the indicator of the enzyme assay. Because of the strong oxidizing capacity of quinonoid dihydropterine, the degree of spontaneous oxidation of NADH by the various substances used in the dihydropterine reductase assay was studied spectrally. A high degree of spontaneous oxidation of NADH by the substrate itself was found, which can be regulated by dithiotreitol, dependent on its concentration. The absorbance increase at 336 nm, due to the non‐quinonoid dihydropterine formed spontaneously from its quinonoid form, strongly interferes with the absorbance decrease at 340 nm, due to the disappearance of NADH. The interference results in a shift of the absorbance maximum of NADH from 340 nm up to higher wavelengths. This phenomenon, expressing itself in various ways in blank and sample, is discussed with relevance to the validity of the current enzyme assays used in a further classification of hyperphenylalaninaemic patients.
Methylmalonic acidaemia due to mutase apoenzyme defect: Responsive to vitamin B12 in intact fibroblasts but notin vivo
Authors: Baumgartner R. , Giardini O. , Cantani A. , Sabetta G. , Castro M. 
Published: June 2005

AbstractCongenital methylmalonic acidaemia (MMA‐aemia) was diagnosed in an 8‐month‐old girl who presented with severe metabolic acidosis, hypoglycaemia and hyperglycinaemia. Vomiting, failure to thrive and apathy first appeared when breast feeding was replaced by a cows' milk formula at the age of 3 months. The patient, unresponsive to OH‐Cbl therapy, was successfully treated with dietary protein restriction and with Shohl's solution. Aged 4 years 9 months, she is in good health. Studies in cultured fibroblasts revealed a defect of the MMA‐CoA mutase apoenzyme. Mutase activity in cell extracts was barely detectable both with and without added coenzyme (Ado‐Cbl). Addition of OH‐Cbl to the culture medium improved overall propionate metabolism in intact fibroblasts but had no effect on mutase activity in cell extracts. These observations point to the presence of a very labile mutant enzyme, suggesting that the patient reported here may be suffering from yet another variant of MMA‐aemia.
Long‐term prognosis in galactosaemia: Results of a survey of 350 cases
Authors: Waggoner D. D. , Buist N. R. M. , Donnell G. N. 
Published: June 2005

SummaryAn international survey of the long term results of treating galactosaemia has shown poor results. These do not seem to be related to any of the relevant variables studied, for example delayed diagnosis or poor dietary compliance.
Culture of galactosaemic fibroblasts in the presence of galactose: Effect of inosine
Authors: Pourci M. L. , Mangeot M. , Soni T. , Lemonnier A. 
Published: June 2005

SummaryFibroblasts from three galactosaemics had no galactose‐1‐phosphate uridyltransferase (GALT) activity. These fibroblast cells were cultured in different media supplemented with dialysed fetal calf serum. Galactosaemic and control cell strains stopped growing in hexose‐free medium. In glucose‐free medium containing galactose, galatosaemic cells, in contrast to control cells, stopped growing after two days and died. In the same medium supplemented with inosine, they exhibited the same growth pattern as the control cell strains although in the presence of high concentrations of galactose‐1‐phosphate (Gal‐1‐P). These findings indicated that the glucose‐free medium containing galactose supplemented with dialysed fetal calf serum and inosine, as a ribose donor, was appropriate for furtherin vitro investigations of galactose metabolism in galactosaemic cells.
Characterization of human fructose‐1,6‐bisphosphatase in control and deficient tissues
Authors: Adams A. , Redden C. , Menahem S. 
Published: June 2005

SummaryThe regulatory properties of human liver and muscle fructose‐1, 6‐bisphosphatases (FBPase) have been studied in control tissues obtained at autopsy and in tissues from a neonate with FBPase deficiency who died as a result of an overwhelming acidosis. Evidence is presented which suggests that the alkaline isoenzyme of FBPase, which is widely regarded as a laboratory artefact, may have an important rolein vivo in the regulation and control of glycolysis and gluconeogenesis. FBPase exhibits the hysteretic and dissociative properties associated with regulatory enzymes, and many of the factors which effect FBPase have inverse effects on phosphofructokinase activity, thus providing an integrated regulatory cycle for the control of the direction and rate of flux through the glycolytic pathway.
Glycogen debranching enzyme deficiency: Long‐term study of serum enzyme activities and clinical features
Authors: Coleman R. A. , Winter H. S. , Wolf B. , Chen Y. ‐T. 
Published: June 2005

SummaryIn glycogen storage disease type III (glycogen debranching enzyme (DE) deficiency), the activities of serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase may be strikingly elevated during childhood but are low during adult life. To determine the pattern of the elevated serum enzyme activities in relationship to diet, the biochemical subtype and clinical symptoms, 13 patients with DE deficiency were studied. Activities of serum aspartate and alanine transaminases, lactate dehydrogenase, and alkaline phosphatase were markedly elevated during infancy. Continued elevation of enzyme activities during childhood appeared to be related to DE deficiency in liver, but unrelated to DE deficiency in muscle. Activity elevations correlated inconsistently with diet and poorly with childhood growth rate or the presence of hypoglycaemia. The serum enzyme activities declined around puberty concomitantly with a decrease in liver size. Although periportal fibrosis and micronodular cirrhosis indicated the presence of hepatocellular damage during childhood, the decline in serum enzyme activities with age and the absence of overt hepatic dysfunction suggest that the fibrotic process may not always progress.
Tryptophan and serotonin metabolism in familial erythrophagocytic lymphohistiocytosis
Authors: Howells D. W. , Hyland K. , Smith I. , Strobel S. 
Published: June 2005

SummaryReduced concentrations of tryptophan and 5‐hydroxyindoleacetic acid (the major CSF metabolite of serotonin) were found in the cerebrospinal fluid of two children with familial erythrophagocytic lymphohistiocytosis. This was associated with elevated cerebrospinal fluid neopterin concentrations indicating increased macrophage activity within the central nervous system. In one child, cytotoxic therapy induced a complete clinical remission and an increase of tryptophan and 5‐hydroxyindoleacetic acid concentrations to normal; during a subsequent relapse, concentrations of these analytes again fell below normal. In the other child, in whom therapy produced only a transient improvement, tryptophan and 5‐hydroxyindoleacetic acid concentrations remained low and the child died. It is likely that increased activity of indoleamine 2,3‐dioxygenase induced by the activation of macrophages was responsible for the disturbance in serotonin and tryptophan homeostasis within the brain. Excessive tryptophan catabolism and the disturbance of serotonin turnover may play a role in the aetiology of the neurological symptoms seen in familial erythrophagocytic lymphohistiocytosis.
Attempted enzyme replacement using human amnion membane implantations in mucopolysaccharidoses
Authors: Muenzer J. , Neufeld E. F. , Constantopoulos G. , Caruso R. C. , Kaiser‐Kupfer M. I. , Pikus A. , Danoff J. , Berry R. R. , McDonald H. D. , Thompson J. N. , Rodén L. , Zasloff M. A. 
Published: June 2005

SummaryAmnion membrane implantation has been proposed as an approach to enzyme replacement in mucopolysaccharidoses. Human amnion membranes have been subcutaneously implanted in the abdominal wall in 19 patients with mucopolysaccharidoses (MPS I, II and III). A protocol was developed for the objective evaluation of experimental treatments of these patients. Systematic evaluation of the clinical status before and 6 months after amnion membrane implantation reveals no change in function except improvement in joint mobility. The sum of all joint movements showed improvement from baseline values to 6 months after implantation by ANOVA followed bypost‐hoc analysis (p<0.056). The only specific joint movements to significantly improve after 6 months were shoulder extension (p<0.01) and hip internal rotation (p<0.05). Serial measurements of the deficient lysosomal enzyme activity in serum and white blood cells did not increase in any patient after amnion membrane implantation. Urinary glycosaminoglycan excretion decreased transiently in 2 of 10 patients after implantation, but a second amnion membrane implantation did not result in any change. Biopsy of the implantation site in 10 patients 6 months after amnion membrane implantation revealed a foreign‐body reaction with giant cell formation and fibrosis and no recognizable amnion membrane tissue. We conclude that human amnion membrane implantation is not an effective therapy in mucopolysaccharidoses.
Oligosaccharides accumulated in the bovineβ‐mannosidosis kidney
Authors: Jones M. Z. , Rathke E. J. S. , Gage D. A. , Costello C. E. , Murakami K. , Ohta M. , Matsuura F. 
Published: June 2005

SummaryThe phenotype of bovineβ‐mannosidosis (β‐mannosidase deficiency), recently identified in Salers cattle, is similar to the caprine form of the disease (Abbittet al., 1991). This investigation was designed to characterize accumulated kidney oligosaccharides in bovineβ‐mannosidosis. Oligosaccharides were extracted from the kidney of an affected Salers calf and purified by chromatographic techniques. The amount of accumulating oligosaccharides in 1 g of wet tissue was about 21µmol. Structures of derivatized oligosaccharides were characterized by high‐performance liquid chromatography, mass spectrometry, methylation analysis and sequential exoglycosidase digestions. The major accumulating oligosaccharides were Manβ1‐4GlcNAc and Manβ1‐4GlcNAcβ1‐4GlcNAc. Oligosaccharides accumulating in minor amounts were Manβ1‐4GlcNAcβ1‐4Manβ1‐4GlcNAc, Manα1‐6Manβ1‐4GlcNAcβ1‐4GlcNAc and Manβ1‐4GlcNAcβ1‐4Manβ1‐4GlcNAcβ1‐4GlcNAc. As in caprineβ‐mannosidosis, oligosaccharides with terminalβ‐mannose residues and cleaved as well as uncleaved chitobiose linkages were identified in bovineβ‐mannosidosis kidney. The accumulating oligosaccharides in tissue were thus identical in bovine and caprineβ‐mannosidosis; however, the source of the novel oligosaccharides remains to be determined.
Gonadal mosaicism in a family with adrenoleukodystrophy: Molecular diagnosis of carrier status among daughters of a gonadal mosaic when direct detection of the mutation is not possible
Authors: Graham G. E. , MacLeod P. M. , Lillicrap D. P. , Bridge P. J. 
Published: June 2005

SummaryAdrenoleukodystrophy is a severe, X‐linked neurological disease that has been shown to be linked to DNA markers from Xq28. We tested several families with these markers and, in one family, found two apparent recombination events between DXS52 and the disease. Expansion of the study to include other tests and several others markers from Xq28 led us to conclude that recombination probably had not occurred and that, instead, the mutation in this family had a mitotic origin and that the grandmother was a gonadal mosaic. For genes that have been cloned, it is often possible to demonstrate the presence or absence of a specific mutation in such families and to determine carrier status on that basis. This is not possible when the gene has not been cloned. We therefore describe a method that can be employed by a molecular diagnostic laboratory to discriminate between people who inherit the same RFLP halpotype, with or without the mutation, from a parent with gonadal mosaicism in diseases where direct gene analysis is not yet possible.
Quantification ofN‐acetyl‐l‐aspartic acid in urine by isotope dilution gas chromatography‐mass spectrometry
Authors: Kelley R. I. , Stamas J. N. 
Published: June 2005

SummaryA method for quantification ofN‐acetyl‐l‐aspartic acid by isotope dilution gas chromatography‐mass spectrometry using15N‐[2H3]acetyl‐l‐aspartic acid is described. The method is sufficiently sensitive to be used with solvent extraction techniques commonly employed for urinary organic acid analysis. The mean concentration ofN‐acetyl‐l‐aspartic acid in 80 normal and abnormal control urine specimens was 19.7±10.8 mg/g creatinine (12.7±7.8 mmol/mol creatinine). Seven patients, ages 9 months to 7 years, with Canavan‐van Bogaert syndrome had urinaryN‐acetyl‐l‐aspartic acid levels from 606 to 4760 mg/g creatinine. The method can also be used with cerebrospinal fluid, in which the concentration ofN‐acetyl‐l‐aspartic acid is about one‐tenth of that in urine.
Biochemical basis of hypoxanthine‐guanine phosphoribosyltransferase deficiency in nine families
Authors: Keough D. T. , Gordon R. B. , de Jersey J. , Emmerson B. T. 
Published: June 2005

SummaryThe concentration of hypoxanthine‐guanine phosphoribosyltransferase (HPRT) cross‐reacting material (CRM) was determined in haemolysates and/or lymphoblast lysates from nine patients with complete or partial deficiency of HPRT activity. Two of the patients had the fully developed Lesch‐Nyhan syndrome and although they had undetectable HPRT activity, small amounts of CRM were found. HPRT‐specific mRNA was not detected in lymphoblast lysates from one of these patients, while lysates from the other had a much reduced concentration. Samples from three patients with <0.1% of normal HPRT activity but with minor or no neurological manifestations were also found to contain small amounts of CRM. The other four patients whose HPRT activities ranged from 3 to 10% of normal were found to have CRM concentrations which varied from 26 to 100% of normal. In one patient with a partial deficiency theKm for 5‐phospho‐α‐d‐ribosyl‐1‐pyrophosphate was five times normal.
Use of platelets, mononuclear and polymorphonuclear cells in the diagnosis of glycogen storage disease type VI
Authors: Dahan N. , Baussan C. , Moatti N. , Lemonnier A. 
Published: June 2005

SummaryWe determined glycogen concentration and phosphorylase ‘a+b’ and phosphorylase a activities in platelets, mononuclear and polymorphonuclear cells from control subjects and patients with phosphorylase kinase deficiency (glycogen storage disease IX) and liver phosphorylase deficiency (glycogen storage disease VI). Variations according to cellular type and to subjects' age (1–40 years) were established. Variable glycogen overloading was found in all our patients. Glycogen storage disease (GSD) VI was characterized by a diminished total phosphorylase activity with a low or normal a/(a+b) ratio of phosphorylase activity. GSD IX was characterized by a very low residual activity of phosphorylase a with an ‘a+b’ activity low or normal.
Excretion of phenylpyruvic, 4‐hydroxyphenylpyruvic and indolyl‐3‐acetic acids by the skin fibroblasts from a phenylketonuric child
Authors: Antoshechkin A. G. , Zuyeva L. A. , Maximova L. A. 
Published: June 2005

SummaryHigh‐resolution gas chromatography and mass spectrometry have been used to analyse the changing chemical composition of the culture medium upon the growth of skin fibroblasts from a healthy individual and from a classical phenylketonuric (PKU) patient. The PKU fibroblasts, unlike normal ones, were found to excrete into the culture medium phenylpyruvate, 4‐hydroxyphenylpyruvate, indolyl‐3‐acetate and an unidentified metabolite containing the phenyl group. This testifies to the disturbed metabolism of phenylalanine, tyrosine and tryptophan in the PKU fibroblasts. This seems to be the reason for their reduced viability as compared with normal fibroblasts.
Peroxisomal integral membrane proteins in livers of patients with Zellweger syndrome, infantile Refsum's disease and X‐linked adrenoleukodystrophy
Authors: Small G. M. , Santos M. J. , Imanaka T. , Poulos A. , Danks D. M. , Moser H. W. , Lazarow P. B. 
Published: June 2005

SummaryLivers from seven patients with peroxisome disorders, three with Zellweger syndrome, one with infantile Refsum's syndrome and three with X‐linked adrenoleukodystrophy, were analysed by immunoblotting. The bifunctional protein catalysing two peroxisomal β‐oxidation reactions was deficient in all Zellweger livers and in the infantile Refsum's liver, consistent with the absence of morphologically recognizable peroxisomes. Three peroxisomal integral membrane proteins (IMPs) (69, 53 and 22 kDa) were present in normal amounts in all the Zellweger and adrenoleukodystrophy samples and they sedimented in a membrane fraction. These membrane proteins were also present in the infantile Refsum's liver. We suggest, on the basis of these results, that aberrant peroxisomal membranes may be present in Zellweger syndrome and that the defect is in the transport of matrix proteins into the organelle.
Polarizing inclusions in some organs of children with congenital peroxisomal diseases (Zellweger's, Refsum's, chondrodysplasia punctata (rhizomelic form), X‐linked adrenoleukodystrophy)
Authors: Kerckaert I. , Dingemans K. P. , Heymans H. S. A. , Vamecq J. , Roels F. 
Published: June 2005

SummaryPolarizing material has been reported in the liver of children with infantile Refsum's disease (IRD) and was absent in two patients with the cerebro‐hepato‐renal syndrome of Zellweger (CHRS). We examined in polarized light 15 liver biopsy and autopsy samples from six other patients with the cerebro‐hepato‐renal syndrome of Zellweger, two with the rhizomelic form of chondrodysplasia punctata (rCDP) and two with X‐linked adrenoleukodystrophy (ALD), all conditions with deficient peroxisomes. Two types of birefringent inclusions were found in CHRS only: the first is transparent in bright field, the second appears as brown granules or rods, similar to lipofuscins. As in IRD large PAS‐positive macrophage‐like cells contain the transparent type. Electron microscopical investigation of these cells shows trilaminar structures within membrane‐bound organelles. The two types were also seen in kidney and brown adipose tissue, the first type in pancreas, the second type in adrenal gland; no such was observed in myocardium or in thyroid gland (CHRS). No birefringent inclusions were present in rCDP and ALD. The nature of the inclusions is still unclear. An accumulation of the transparent polarizing material with increasing age of the patients is most likely.