bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation and function of the mitochondrial genome
Authors: Jeong‐Yu S. , Clayton D. A. 
Published: June 2005

SummaryMolecular changes in human mitochondrial DNA play a significant role in causing certain human diseases. Mitochondrial DNA mutations range from single base pair changes in the 16.5 kilobase pair genome up to large deletions and rearrangements. This report summarizes the current overall understanding of the mode and mechanism of mitochondrial DNA replication and transcription, and how this relates to mitochondrial gene expression, which is essential for cellular energy production and organelle biogenesis. Special attention is given to recent findings that bear on early steps in the process of transcription and, in turn, the consequences for initiating DNA replication
Genetic counselling and prenatal diagnosis in disorders of the mitochondrial energy metabolism
Authors: Ruitenbeek W. , Wendel U. , Hamel B. C. J. , Trijbels J. M. F. 
Published: June 2005

SummaryPoint mutations in mitochondrial DNA, as found in MELAS, MERRF, NARP and other syndromes, are inherited via the maternal lineage. Genetic counselling can be beneficial, but prenatal diagnosis is not advantageous in these syndromes. Empirical data about the recurrence risk can be applied in Leber disease (LHON). Mitochondrial disorders not associated with a point mutation have a sporadic nature (large deletions/duplications in mitochondrial DNA) or are transmitted according to Mendelian laws. Autosomal dominant inheritance is likely to be found in disorders with depletion of mitochondrial DNA. X‐linked mode of inheritance is seen in Menkes disease, Barth syndrome, and in deficiencies of the E1α subunit of the pyruvate dehydrogenase complex. Mutation analysis or linkage studies can be applied for carrier detection and prenatal diagnosis in these three types of mitochondriopathies. The majority of the disorders with a disturbed mitochondrial energy metabolism are likely inherited in an autosomal recessive mode. Prenatal diagnosis can be performed in the cases of cytochromec oxidase and NADH dehydrogenase deficiencies in chorionic villi in selected families.
Pyruvate carboxylase deficiencies: Complementation studies between “French” and “American” phenotypes in cultured fibroblasts
Authors: Augereau C. , Pham Dinh D. , Moncion A. , Marsac C. , Saudubray J. M. , Robinson B. H. 
Published: June 2005

AbstractPyruvate carboxylase (PC) deficiencies (McKusick 26615) are heterogeneous clinically and biochemically. We performed a complementation study with fibroblast strains from seven patients, (four patients with “French” phenotype, two patients with “American” phenotype, one patient with biotin responsive multiple carboxylase deficiency, MCD). The six isolated pyruvate carboxylase mutants (two cross‐reacting material CRM −ve and four CRM +ve) failed to complement each other, but did complement a form of biotin responsive MCD.
Biochemical nature of pyruvate dehydrogenase complex in the patient with primary lactic acidaemia
Authors: Kitano A. , Endo F. , Kuroda Y. , Aso S. , Kawasaki T. , Matsuda I. 
Published: June 2005

SummaryThe biochemical nature of the pyruvate dehydrogenase complex (PDHC) in muscle was studied in a patient with pyruvate dehydrogenase complex deficiency. The enzyme activity was approximately 30% of the control level and the apparentKm value of the enzyme was similar to the control value. The immunoblot pattern of each subunit protein, E1α, E1β, the component X, E2 and E3, was comparable to that of the control on both one‐and two‐dimensional electrophoresis, the staining of each subunit protein being reduced in intensity, corresponding to the reduced enzyme activity. The enzyme deficiency is likely to be quantitative rather than qualitative, although the actual mechanism is unknown.
Deficient oxidation of trihydroxycoprostanic acid in liver homogenates from patients with peroxisomal diseases
Authors: Casteels M. , Van Roermund C. W. T. , Schepers L. , Govaert L. , Eyssen H. J. , Mannaerts G. P. , Wanders R. J. A. 
Published: June 2005

SummaryThe activation of palmitate and trihydroxycoprostanic acid and the peroxisomal oxidation of palmitate, trihydroxycoprostanic acid and their CoA esters were measured in homogenates prepared from fresh liver tissue of patients undergoing hepatic surgery and from frozen postmortem liver specimens of controls, patients with Zellweger syndrome and a patient with pseudo‐Zellweger syndrome, a deficiency of peroxisomal 3‐oxoacyl‐CoA thiolase. In contrast to the findings in control livers, peroxisomal β‐oxidation of palmitate and of palmitoyl‐CoA was severely impaired, and oxidation of trihydroxycoprostanic acid and its CoA ester could not be detected in the livers of the patients affected by peroxisomal diseases. The finding in this paper, that the oxidation of trihydroxycoprostanoyl‐CoA can be measured reliably in small amounts of human liver, will be of valuable help in the differential diagnosis and classification of peroxisomal disorders and will help to elucidate the exact nature of some of the defects present in these disorders.
Streptozotocin‐induced diabetes is not a model for methylmalonic acidaemia
Authors: Bailey L. B. , Molloy A. , Scott J. , Rice D. 
Published: June 2005

SummaryThe streptozotocin‐treated diabetic rat was not found to be a suitable animal model for methylmalonic acidaemia as previously described. Urinary methylmalonic acid (MMA) was measured in adult Wistar rats prior to and following injection of streptozotocin (40 mg/kg). Plasma and tissue MMA levels were measured following the induction of diabetes and compared with data from control rats. MMA levels were determined by a gas chromatographic‐mass spectrometric method (McMurrayet al., 1986). Diabetes was confirmed by the 10 × increase in 24h urine volume; glycosuria; glycaemia; and weight loss. Urinary MMA excreted did not change during the 11 week diabetic period and there was no difference between the pre‐ and post‐diabetic phases (p<0.05). Plasma and tissue MMA concentrations were not elevated in this diabetic animal model. Also in contrast to earlier reports, the vitamin B12 levels of the diabetic rats were not elevated compared to controls (p<0.05).
Uridine nucleotide sugars in erythrocytes of patients with galactokinase deficiency
Authors: Xu Y. ‐K. , Ng W. G. , Kaufman F. R. , Donnell G. N. 
Published: June 2005

SummaryThe levels of UDPglucose and UDPgalactose (UDPGal) have been measured in erythrocytes of seven patients with galactokinase deficiency. Normal levels of UDPGal were found in all patients with galactokinase deficiency (McKusick 23020). This is in contrast with reduced values of UDPGal found in patients with classical galactosaemia who have complete absence of galactose‐1‐phosphate uridyl transferase activity. It was demonstrated that patients with galactokinase deficiency had an incomplete enzyme block in erythrocytes by direct enzyme assay, by14CO2 production from [1‐14C]galactose, and by the appearance of labelled intermediates, notably galactose‐1‐phosphate and UDPhexose.
The management of breast feeding among infants with phenylketonuria
Authors: McCabe L. , Ernest A. E. , Neifert M. R. , Yannicelli S. , Nord A. M. , Garry P. J. , McCabe E. R. B. 
Published: June 2005

SummaryTreatment for phenylketonuria (PKU) involves using low phenylalanine or phenylalanine‐free formulas and supplementation with sufficient phenylalanine for normal growth and development. Eighteen infants with phenylketonuria who received breast milk as their primary phenylalanine source were compared with ten other infants with PKU who received their phenylalanine primarily from infant formulas. There were no significant differences between breast‐fed and formula‐fed infants for serum phenylalanine, serum tyrosine, length, weight, head circumference, haematocrit, haemoglobin, serum iron, total iron binding capacity, percentage iron saturation, ferritin, plasma zinc and total calorie intake. Breast‐fed infants did show lower mean corpuscular volume at 3 months and 6 months of age. Breast‐fed infants had lower phenylalanine intake at 2, 4, 5 and 6 months of age. Breast‐fed infants at 1, 2, 3, 4, 5 and 6 months of age had lower protein intake. Breast feeding may be continued in the newly diagnosed phenylketonuric infant without any apparent adverse nutritional consequences.
Renal failure in adult patients with hereditary tyrosinaemia type I
Authors: Kvittingen E. A. , Talseth T. , Halvorsen S. , Jakobs C. , Hovig T. , Flatmark A. 
Published: June 2005

SummaryAn adult patient with hereditary tyrosinaemia type I who developed renal failure is reported. She received a renal transplant at the age of 23 years. In childhood her kidney disease was dominated by multiple tubular defects with resulting hypophosphataemic rickets. Metabolic acidosis was the most prominent feature in the years preceding the transplantation. Her kidneys were contracted to 40 g. The major morphological finding was that of a tubulointerstitial nephropathy. Liver biopsies taken at the ages of 5.5 and 23 years showed cirrhotic changes. Crystalloid inclusions in the liver mitochondriae were a prominent finding on electron microscopy. Fumarylacetoacetase was deficient in liver, kidneys, fibroblasts and lymphocytes. The typical biochemical parameters of tyrosinaemia, succinylacetone,p‐hydroxyphenyllactate,p‐hydroxyphenylpyruvate and serum tyrosine were only slightly elevated. A brief history of a second adult tyrosinaemia patient with decreasing renal function is also given.
Presence in human cells and tissues of two prolidases and their alteration in prolidase deficiency
Authors: Butterworth J. , Priestman D. A. 
Published: June 2005

AbstractTwo forms of prolidase can be separated for all the human cells and tissues examined by DEAE‐cellulose column chromatography or batch methods. Serum had a very low prolidase activity eluting as a single peak prior to tissue peak I prolidase. Analysis of the two peaks can readily be carried out using white blood cells, cultured skin fibroblasts and amniotic fluid cells. Dialysis inactivated peak II prolidase although the loss can be prevented by the presence of dithiothreitol. The two peaks differed in their response to Mn2+, substrate specificity, heat stability and inhibition byp‐hydroxymercuribenzoate. In two unrelated cases of prolidase deficiency, fibroblast peak I was markedly reduced, although still detectable, whereas peak II was active against all the substrates, except for a 90% reduction against glycyl‐l‐proline. The properties of peak II were altered in the disease. The results imply that the two forms of prolidase are structurally related.
Disturbed metabolism of copper and zinc in aspartylglycosaminuria: Possible involvement with connective tissue changes
Authors: Näntö‐Salonen K. , Halme T. , Penttinen R. , Langevelde F. V. , Vis R. D. , Alfthan G. 
Published: June 2005

AbstractIn aspartylglycosaminuria (AGU), a lysosomal storage disorder of glycoprotein degradation, there are some abnormalities in collagen and proteoglycan metabolism. Because of earlier observations suggesting a disturbance of copper balance, the metabolism of copper and zinc was studied in more detail to find out if possible trace metal disturbances could be correlated with connective tissue disorder. Highly elevated copper concentrations in the hair and significantly reduced zinc levels in serum and urine were detected in AGU patients indicating a disturbance of trace element balance. However, the patients had normal serum copper levels, and the concentrations of zinc and copper in cultured fibroblasts did not differ from those of control cells. Normal lysyl oxidase activities in cell culture indicate that collagen cross‐link formation is not affected. The changes in copper and zinc balance are probably secondary to the basic enzyme deficiency, and may contribute to the development of the clinical signs and symptoms of AGU although the mechanisms involved are not yet understood.
Identification of 3α,7α,12α‐trihydroxy‐5β‐cholestan‐26‐oic acid, an intermediate in cholic acid synthesis, in the plasma of patients with infantile Refsum's disease
Authors: Poulos A. , Whiting M. J. 
Published: June 2005

AbstractThe plasma bile acid profiles of three children with the inherited metabolic disorder, infantile Refsum's disease, were found to contain 3α,7α,12α‐trihydroxy‐5β‐cholestan‐26‐oic acid. This intermediate in the synthesis of cholic acid was identified by combined gas‐liquid chromatography‐mass spectrometry and accounted for approximately 25% of the total bile acids which were present at elevated concentrations in plasma. Infantile Refsum's disease appears to share several biochemical features with the cerebro‐hepato‐renal syndrome (Zellweger's disease), including abnormal bile acid metabolism.
Comparative pathology of the canine model of glycogen storage disease type II (Pompe's disease)
Authors: Walvoort H. C. , Dormans J. A. M. A. , van den Ingh T. S. G. A. M. 
Published: June 2005

AbstractThe pathology of canine glycogen storage disease type II (acid α‐glucosidase deficiency, GSD II) was studied in three genetically related Lapland dogs and compared to the pathology of human GSD II (McKusick 23230). Canine GSD II closely parallels the infantile form of the human disease, except for the presence of oesophageal dilatation. Generalized glycogen storage particularly affected muscular tissues (skeletal, oesophageal, cardiac and smooth muscle). The altered cells showed glycogen accumulation in the cytosol and in autophagic membrane‐bound vacuoles (glycogenosomes). They also showed increased acid phosphatase activity consistent with the lysosomal nature of this storage disorder. The cytopathology in canine and human GSD II appears to evolve from segregation of glycogen during regular cellular autophagy, phagolysosomal accumulation of the undigested glycogen, and eventually rupture of distended glycogenosomes. This study indicates that the usefulness of canine GSD II as an animal model of human disease, extends to the area of pathogenesis.
Methylcitrate in maternal urine during a pregnancy with a fetus affected with propionic acidaemia
Authors: Aramaki S. , Lehotay D. , Nyhan W. L. , MacLeod P. M. , Sweetman L. 
Published: June 2005

SummaryPatients homozygous for propionic acidaemia have high levels of methylcitric acid in urine while heterozygotes have normal levels. Methylcitric acid was determined by stable isotope dilution gas chromatography‐mass spectrometry in maternal urine during a pregnancy with a fetus affected with propionic acidaemia. Although the levels increased linearly between 23 and 39 weeks of gestation, the levels were not significantly elevated above normal until after 30 weeks of gestation. Thus, determination of methylcitric acid in maternal urine is not of value for early prenatal diagnosis of propionic acidaemia.
Persistent hyperkalaemia in vitamin B12 unresponsive methylmalonic acidaemia
Authors: Morita J. , Ito Y. , Yoshino M. , Koga Y. , Yano S. , Yoshida I. , Yamashita F. 
Published: June 2005

SummaryPersistent hyperkalaemia was found in a patient with vitamin B12 unresponsive methylmalonic acidaemia associated with hyperuricaemia. At 3 years and 8 months of age, a serum potassium level of 6.8 mmol L−1 was found when blood gas measurement was normal. One year later azotaemia was noted. At the age of 5 years, renal function studies disclosed hyperaldosteronism, decreased creatinine clearance, reduction of the reabsorption of sodium at distal diluting segments and inadequate concentration of urine at the collecting ducts. The reduction of the reabsorption of sodium, which may have resulted in decreased potassium excretion, and the decrease in glomerular filtration rate, together with the superimposed excess intake of potassium, appeared to be responsible for the hyperkalaemia. Dietary potassium restriction was effective in suppressing the hyperkalaemia.
Mild variant of argininosuccinic aciduria
Authors: Schutgens R. B. H. , Beemer F. A. , Tegelaers W. H. H. , de Groot W. P. 
Published: June 2005

AbstractA 7 1/2‐year‐old boy with a massive excretion of argininosuccinic acid is described. He exhibited only moderate mental retardation, cerebellar ataxia and both abnormal hair and skin. Argininosuccinate lyase activity in the erythrocytes of his parents and his sister was in the range expected for heterozygotes. The patient was put on a low protein diet with arginine supplementation and improved clinically and biochemically on this regime. The variability of the phenotypic expression of argininosuccinate lyase deficiency is stressed.
Metabolism of glycine in the normal individual and in patients with non‐ketotic hyperglycinaemia
Authors: Nyhan W. L. 
Published: June 2005

AbstractThe metabolism of glycine is characterized largely by synthetic reactions. Even the catabolism of glycine appears to foster synthetic reactions because its cleavage leads to the formation of a one‐carbon tetrahydrofolate compound which can serve in a variety of synthetic pathways. In non‐ketotic hyperglycinaemia the activity of the glycine cleavage reaction is defective. This has been demonstratedin vivo andin vitro using liver and brain.
Ultrastructural changes in fibroblast mitochondria of a patient with HHH‐syndrome
Authors: Metoki K. , Hommes F. A. , Dyken P. , Kelloes C. , Trefz J. 
Published: June 2005

AbstractElectron micrographs of fibroblasts of an HHH‐syndrome patient showed abnormal structures, similar, but not identical, to those observed in the liver of such patients. It is suggested that incorporation of a mutated protein into the inner mitochondrial membrane gives rise to a rearrangement of that membrane, resulting in unusual structures.
β‐Mannosidase in human leukocytes and fibroblasts
Authors: Panday R. S. , van Diggelen O. P. , Kleijer W. J. , Niermeijer M. F. 
Published: June 2005

AbstractIn human leukocytes and fibroblasts β‐mannosidase activity has a unimodal pH optimum (4.0–4.5). Markedly reduced activity is found in I‐cell disease. Normal activities in human fibroblasts are ten times higher than in the goat, in which species a deficiency disease has been described.
The effect of treatment on zinc, copper and calcium status in children with phenylketonuria
Authors: Taylor C. J. , Moore G. , Davidson D. C. 
Published: June 2005

AbstractThe trace element status of 25 children receiving a low phenylalanine diet for a treatment of phenylketonuria was studied using hair and serum samples. Hair trace element and calcium concentrations were assayed using X‐ray microanalysis and compared with samples from sibling controls. Plasma, zinc and copper levels were compared with unselected hospital attenders. PKU patients were found to have significantly lower hair zinc (P<0.001) and calcium (P<0.01) concentrations and significantly higher hair copper (P<0.001) concentrations compared with controls. Plasma zinc levels were below the lower limit of normal (9.6µmol l−1) in 8 of 19 patients (42%) in whom it was measured. The relative zinc deficiency in PKU patients may result from a competitive inhibition of absorption by copper or other metals supplemented in the diet.
Copper utilization in cultured skin fibroblasts of the mottled mouse, an animal model for Menkes' kinky hair syndrome
Authors: Packman S. , Chin P. , O'Toole C. 
Published: June 2005

AbstractAn animal model for Menkes' kinky hair syndrome is provided by mice mutant at the X‐linked mottled locus. Two mechanisms have been invoked to explain disease manifestations in mottled and in kinky hair syndrome: (i) relative tissue copper deficiencies and corresponding reductions in cuproenzyme activities; or (ii) defective intracellular copper utilization, with impaired intracellular translocation to cuproenzymes or to copper‐dependent processes. We addressed the second possibility through measurements of soluble superoxide dismutase (SOD‐1) in cytosol extracts of confluent mottled (blotchy) cultured skin fibroblasts. At comparable intracellular copper concentrations over a broad range, SOD‐1 specific activities in the mutant cells were not distinguishable from those in controls, or, in some instances, were actually higher. These data suggest that the excess copper anomalously sequestered in a cell expressing the mutation remains available for binding to a cytosolic cuproenzyme. When taken together with data in other systems, the results are consistent with the thesis that the basic lesion in blotchy may primarily affect copper transport or delivery to specific copper transport systems.
Tay‐sachs disease heterozygote detection in Brazil: Comparison between tears and leukocytes as β‐hexosaminidase a source
Authors: Buchalter M. S. , Wannmacher C. M. D. , Wajner M. 
Published: June 2005

AbstractHexosaminidase A activities were determined in tears and peripheral leukocytes of carriers and noncarriers for Tay‐Sachs Disease (TSD) as a percentage of total hexosaminidase activity. Correlation between enzyme activities in tears and leukocytes was highly significant (r=0.75,p<0.01). Compared to leukocytes, screening in tears revealed 100% sensitivity, 100% negative predictive value, 86% specificity and 80% positive predictive value. These results indicate that tears are a satisfactory material for mass‐screening of TSD‐carrier state, but positive results must be confirmed in peripheral leukocytes.Seven heterozygotes were detected among 298 young Ashkenazi Jewish volunteers screened, giving an adjusted frequency of the TSD gene of 0.024.
Multiple sulphatase deficiency in homozygotic twins
Authors: Nevšímalová S. , Elleder M. , Šmíd F. , Zemánková M. 
Published: June 2005

AbstractMultiple sulphatase deficiency was studied in 3 siblings — one pair of monozygotic twins and their sister. The children's psychomotor development was arrested at the age of 18 to 24 months, and the hypotonic syndrome combined with signs of spasticity appeared. There was marked hepatosplenomegaly, conspicuously dry scaly skin with the decortication syndrome developing and persisting in the presence of pronounced cachexia. Also present were numerous X‐ray abnormalities, metachromatically staining granules in the urine, and Alder‐Reilly's bodies in the blood leukocytes and in specimens of bone marrow. Liver, skin and muscle biopsies performed simultaneously revealed accumulations of water‐soluble mucopolysaccharides and deposits of sulphatides in the two twins. Enzyme assays demonstrated arylsulphatase A and B deficiency. The diagnosis was subsequently confirmed at all the three siblings' postmortem examinations.
Biochemical and clinical changes in Wilson's disease heterozygotes
Authors: Mareček Z. , Nevšímalová S. 
Published: June 2005

AbstractThis paper reports on a study of the heterozygous children of patients with Wilson's disease. A total of 16 children of 10 patients with the disease were followed up. Detailed biochemical, clinical and EEG tests were done. Nearly all the children were found to have reduced serum copper and caeruloplasmin levels and high rates of urine copper excretion following exposure to penicillamine. These findings were different from the results obtained in adult heterozygous carriers. Thirty per cent of the children had pathological neurological findings, and EEG abnormalities were found in 75%.