bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality and Ecology of Adversity as Common Mechanisms of Risk and Resilience
Authors: Sandler Irwin 
Published: December 2002

AbstractThis paper proposes common mechanisms to explain the effects of adversities and of resources that promote resilience. Adversities threaten the satisfaction of basic human needs and the acquisitions of competencies to carry out valued social roles. Adversities can also be characterized in terms of their ecological properties of occurrence in time, and place. Resilience resources at the individual, microsystem and macro levels reduce the negative effects of adversities through their effects on satisfaction of basic human needs and their effects on the occurrence of adversities. The effects of resilience resources are described as preventive, protective and promotive. Implications are presented for the development of interventions to promote resilience.
Biochemical and molecular analysis of an X‐linked case of Leigh syndrome associated with thiamin‐responsive pyruvate dehydrogenase deficiency
Authors: Naito E. , Ito M. , Yokota I. , Saijo T. , Matsuda J. , Osaka H. , Kimura S. , Kuroda Y. 
Published: December 2002

AbstractWe report molecular analysis of thiamin‐responsive pyruvate dehydrogenase complex (PDHC) deficiency in a patient with an X‐linked form of Leigh syndrome. PDHC activity in cultured lymphoblastoid cells of this patient and his asymptomatic mother were normal in the presence of a high thiamin pyrophosphate (TPP) concentration (0.4 mmol/L). However, in the presence of a low concentration (1 X 10‐4 mmol/L) of TPP, the activity was significantly decreased, indicating that PDHC deficiency in this patient was due to decreased affinity of PDHC for TPP. The patient's older brother also was diagnosed as PDHC deficiency with Leigh syndrome, suggesting that PDHC deficiency in these two brothers was not a de novo mutation. Sequencing of the X‐linked PDHC E1 α subunit revealed a C → G point mutation at nucleotide 787, resulting in a substitution of glycine for arginine 263. Restriction enzyme analysis of the E1α gene revealed that the mother was a heterozygote, indicating that thiamin‐responsive PDHC deficiency associated with Leigh syndrome due to this mutation is transmitted by X‐linked inheritance.
The human arginases and arginase deficiency
Authors: Iyer R. , Jenkinson C. P. , Vockley J. G. , Kern R. M. , Grody W. W. , Cederbaum S. 
Published: December 2002

AbstractArginase is the final enzyme in the urea cycle. Its deficiency is the least frequently described disorder of this cycle. It results primarily in elevated blood arginine, and less frequently in either persistent or acute elevations in blood ammonia. This appears to be due to a second arginase locus, expressed primarily in the kidney, which can be recruited to compensate, in part, for the deficiency of liver arginase. The liver arginase gene structure permitted study of the molecular pathology of patients with the disorder and the results of these studies and the inferences about the protein structure are presented. The conserved regions among all arginases allowed the cloning of AII, the second arginase isoform. It has been localized to the mitochondrion and is thought to be involved in ornithine biosynthesis. It shares the major conserved protein sequences, and structural features of liver arginase gene are also conserved. When AI and AII from various species are compared, it appears that the two diverged some time prior to the evolution of amphibians. The evidence for the role of AII in nitric oxide and polyamine metabolism is presented and this appears consonant with the data on the tissue distribution.
Continuous venovenous haemodiafiltration in the acute phase of neonatal maple syrup urine disease
Authors: Jouvet P. , Poggi F. , Rabier D. , Michel J. L. , Hubert P. , Sposito M. , Saudubray J. M. , Man N. K. 
Published: December 2002

AbstractMaple syrup urine disease results in accumulation of leucine and its metabolites, which may lead in the long term to neurological dysfunction. In acute neonatal crises, large amounts of leucine may be removed by continuous venovenous haemofiltration. This extracorporeal technique has its risks and hazards, which increase with duration of treatment. We report three neonates in life‐threatening conditions due to maple syrup urine disease, treated for not more than 12h with various continuous venovenous techniques: continuous haemofiltration, haemodiafiltration and haemodialysis. The efficiency of and tolerance to these techniques was evaluated. For all three patients, plasma leucine levels decreased dramatically from 2186, 3818 and 2536 µmol/L to 1131, 1275 and 488 µmol/L, respectively. Leucine clearance obtained was 4.28 ml/min in haemodiafiltration. Their patients' neurological status improved rapidly and they have a normal developmental quotient at 22 months, 13 months, and 11 months of age, respectively. Tolerance was good except for hypothermia and drop in haematocrit in all cases. Haemodiafiltration management was more cumbersome and time consuming because it required continual adjustment of the substitution fluid flow rate to precisely balance inflow and outflow rates. We recommend continuous venovenous haemodialysis as the therapy of choice. It might be anticipated that improvement of this technique, by increasing dialysate flow rate and blood flow rate, will allow leucine concentration to be decreased below 1000 µmol/L within 6‐8 h, whatever the initial level.
A new peroxisomal β‐oxidation disorder in twin neonates: Defective oxidation of both cerotic and pristanic acids
Authors: Christensen E. , Pedersen S. Anker , Leth H. , Jakobs C. , Schutgens R. B. H. , Wanders R. J. A. 
Published: December 2002

AbstractTwin brothers were born with clinical symptoms indicating that they were suffering from Zellweger syndrome. However, instead of a generalized peroxisomal dysfunction, only very long‐chain fatty acids and the pristanic acid/phytanic acid ratio were elevated in plasma and decreased oxidation of very long‐chain fatty acids and pristanic acid was the only impairment found in fibroblasts. The other peroxisomal parameters tested were normal, including normal oxidation of phytanic acid and normal activity of dihydroxyacetonephosphate acyltransferase in fibroblasts as well as normal plasma bile acids. Although the biochemical results point to a defect in peroxisomal β‐oxidation, the isolated finding of impaired oxidation of very long‐chain fatty acids and pristanic acid has to our knowledge not been reported previously and is difficult to explain by a deficiency of a known peroxisomal β‐oxidation enzyme.
Plasmalogens and oxidative stress: evidence against a major role of plasmalogens in protection against the superoxide anion radical
Authors: Jansen G. A. , Wanders R. J. A. 
Published: December 2002

AbstractAlthough ether‐linked phospholipids have been known to be constituents of biological membranes for a long time, their physiological function has remained an enigma through the years. Inspired by the suggestion of Zoeller and coworkers that plasmalogens, which are specific types of ether‐linked phospholipids characterized by the occurrence of an α,β‐unsaturated ether bond at the sn‐1 position, are involved in the protection of cells against reactive oxygen species, we studied reactive oxygen species metabolism in cultured human skin fibroblasts. Menadione was used as intracellular generator of reactive oxygen species and cytochrome c as extracellular indicator for the production of reactive oxygen species. The finding that identical results were obtained in control and plasmalogen‐deficient fibroblasts leads us to conclude that plasmalogens do not play a major role in protection against reactive oxygen species.
5α‐Reductase deficiency in patients with micropenis
Authors: Gad Y. Z. , Nasr H. , Mazen I. , Salah N. , El‐Ridi R. 
Published: December 2002

AbstractThe enzyme 5α‐reductase (5αR), by virtue of its peripheral 5α‐reduction of testosterone (T) to dihydrotestosterone (DHT), is believed to play a major role in the differentiation and the subsequent growth of the penis. However, recent studies have reported 5αR deficiency (5αRD) in patients with isolated micropenis and hypothesized that 5αRD is not invariably associated with genital ambiguity. In Egypt, 5αRD has been reported frequently among intersex patients. The aim of this study was to assess the role of 5αRD in the development of micropenis among Egyptian patients with abnormal sexual development. The study included 29 patients who were categorized into three groups (isolated micropenis, 9 patients; microphallus with genital ambiguity, 11 patients; genital ambiguity with normal‐sized phallus, 9 patients). Activity of 5αR was assessed by estimating T/DHT ratios in the basal state in pubertal subjects and following human chorionic gonadotropin (HCG) stimulation test in prepubertals.The results showed that the incidence of 5αRD was much higher in cases of ambiguous genitalia with micropenis (5 families out of 10, 50%) than in those with isolated microphallus (1/9, 11·1%) or those with ambiguous genitalia and normal‐sized phallus (1/8, 12.5%). In conclusion, the study showed that isolated micropenis is a heterogeneous disorder and that 5αRD, despite its relative prevalence in Egypt, has a minimal role in the aetiology. On the other hand, 5αRD seems to correlate with penile length in intersex cases.
Executive function in treated phenylketonuria as measured by the one‐back and two‐back versions of the continuous performance test
Authors: Griffiths P. , Campbell R. , Robinson P. 
Published: December 2002

AbstractThe executive dysfunction hypothesis in treated phenylketonuria was investigated by means of the one‐back and two‐back versions of the continuous performance test. Eleven non‐retarded, primary school‐age children with classical phenylketonuria who had been treated early and continuously were indistinguishable from healthy, matched controls on the measures and test performance was not predicted by historical or concurrent plasma phenylalanine concentrations. Mean lifetime phenylalanine concentrations for the phenylketonuric subjects were within ranges currently recommended as dietary optima in the United Kingdom. The negative neuropsychological test findings add weight to the rationale for this policy.
Two new mutations in the 3′ coding region of the glycogen debranching enzyme in a glycogen storage disease type IIIa Ashkenazi Jewish patient
Authors: Parvari R. , Shen J. , Hershkovitz E. , Chen Y. T. , Moses S. W. 
Published: December 2002

AbstractGlycogen storage disease type III (GSD III) is an autosomal recessive disease caused by the deficiency of glycogen debranching enzyme (AGL). We report the finding of two new mutations in a GSD IIIa Ashkenazi Jewish patient. Both mutations are insertion of an adenine into a stretch of 8 adenines towards the 3′ end of the coding region: one at position 3904 (3904insA) in exon 30, the second at position 4214 (4214insA) in exon 32. The mutations cause frameshifts and premature terminations of the glycogen debranching enzyme, the first causing a frameshift at amino acid 1304, the second causing a frameshift at amino acid 1408 of the total of 1532. These mutations demonstrate the importance of the 125 amino acids at the carboxy‐terminus of the debrancher enzyme for its activity and support the suggestion that the putative glycogen binding domain is located in the carboxy‐terminus of the AGL. The mutations cause distinctive single‐strand conformation polymorphism (SSCP) patterns enabling easy detection.
Subclinical visual impairment in phenylketonuria. A neurophysiological study (VEP‐P) with clinical, biochemical, and neuroradiological (MRI) correlations
Authors: Leuzzi V. , Rinalduzzi S. , Chiarotti F. , Garzia P. , Trasimeni G. , Accornero N. 
Published: December 2002

AbstractDuring detailed visual function testing, pattern‐reversal visual evoked potentials (VEP), generated by different spatial frequencies (3c/d, 1c/d and 0.6c/d) and visual contrasts (100% and 10%) were recorded in 21 adolescent and young adult phenylketonuric (PKU) patients (11 females and 10 males; mean age 14.8 years, range 9–22.8) on and off diet. In 14 of the 21 patients, disease had been detected at neonatal screening and in 7 later. Ten age‐matched healthy subjects acted as controls. Recordings in more than 40% of eyes in the whole group and 30% of eyes in the screening subgroup showed a prolonged P100 latency. All visual pattern stimuli elicited a significantly longer P100 latency in PKU patients than in controls. VEP latencies to 3c/d, 1c/d and 1c/d with 10% contrast – but not to 0.6c/d – were longer in patients off diet than in patients on diet. No differences were found between VEP latencies in early‐ and later‐detected subjects. To study the link between biochemical variables and VEP latencies, we envisaged either a linear relationship between recent exposure to phenylalanine (Phe) and VEP abnormalities or a threshold model considering phenylalanine (Phe) concentrations among the factors influencing VEP latencies. The correlation analysis detected an association between plasma Phe concentrations and abnormal VEP latencies, predicting that plasma Phe concentrations >901 μmol/L would prolong VEP latencies to 1c/d; concentrations >879 μmol/L would prolong latencies to 3c/d; and concentrations >898 μmol/L would prolong latencies to 1c/d with 10% contrast. Finally, our data confirmed a lack of correlation between white‐matter abnormalities on MRI and abnormal VEP latencies. Our findings suggest that in young patients with PKU, prolonged, late exposure to high plasma Phe concentrations induces subclinical visual dysfunction. Although our findings do not allow us to specify the origin of visual system changes in PKU, they favour impairment of the retinal loop as the responsible mechanism.
The recognition of Lesch‐Nyhan syndrome as an inborn error of purine metabolism
Authors: Nyhan W. L. 
Published: December 2002

AbstractLesch‐Nyhan syndrome was first described over thirty years ago. The original patient was a 4‐year‐old boy with neurological abnormalities as well as haematuria. Crystals in his urine were identified and confirmed to be uric acid. The massive excretion of this purine led to metabolic studies using isotopically labelled uric acid to study turnover rates. Clues to the site of the enzyme defect resulted from studies with the immunosuppressive agent azathioprine, which normally causes uric acid concentrations to fall in blood and urine but was without effect in a Lesch‐Nyhan patient. A deficiency of hypoxanthine phosphoribosyltransferase (HPRT) activity explained this observation in Lesch‐Nyhan patients. Subsequent studies have indicated that the degree of HPRT deficiency appears to determine the severity of the disease. Molecular studies have shown that most families carry a unique mutation. Attempts are being made to correlate the type and site of a specific mutation with a particular phenotype.
Highly increased CSF concentrations of cholesterol precursors in Smith‐Lemli‐Opitz syndrome
Authors: van Rooij A. , Nijenhuis A. A. , Wijburg F. A. , Schutgens R. B. H. 
Published: December 2002

AbstractThe Smith‐Lemli‐Opitz syndrome is a genetic disorder characterized by typical clinical features including reduced myelination of both brain and peripheral nervous system and defective cholesterol biosynthesis. In patients this results in very low cholesterol concentrations and accumulation of cholesterol precursors in plasma, tissues, cultured cells and faeces. We now show that the cholesterol concentration in CSF of Smith‐Lemli‐Opitz patients is markedly decreased and that 7‐ and 8‐dehydrocholesterol concentrations are highly increased in comparison to controls. Moreover, dietary treatment of patients with cholesterol seems not to affect CSF cholesterol concentration.
Neonatal neurological assessment of offspring in maternal phenylketonuria
Authors: Waisbren S.E. , Chang P. , Levy H. L. , Shifrin H. , Allred E. , Azen C. , de la Cruz F. , Hanley W. , Koch R. , Matalon R. , Rouse B. 
Published: December 2002

AbstractThis study assesses the impact of prenatal and postnatal factors in maternal phenylketonuria (PKU). The Dubowitz Neurological Assessment of the Preterm and Full‐term Newborn Infant was administered within the first 8 days of life to 56 offspring of women with PKU and 45 controls. Follow‐up testing of the maternal PKU offspring at age 1 year consisted of the Bayley Scales of Infant Development and the Receptive‐Expressive Emergent Language Scale (REEL). In addition, the Home Observation for Measurement of the Environment (HOME Scale) was given. Birth weight was lower (z = 2.0, p = 0.045), birth length was lower (z = 2.1, p = 0.03) and birth head circumference was smaller (z = 3.5, p = 0.0005) in the maternal PKU offspring than in the control infants. Examiners rated 29% of the maternal PKU offspring and 9% of the control infants abnormal (Fisher's exact test, p = 0.01). At 1 year of age, 19% of the maternal PKU offspring attained a Bayley Developmental Quotient (DQ) and a score on the Bayley Motor Scale below 85; 19% had receptive language delay; and 26% had expressive language delay. The gestational age at which the mother attained metabolic control was an important factor associated with birth measurements, the Dubowitz Rating and subsequent developmental scores. The Dubowitz Neurological Assessment score did not predict developmental outcome (chi‐square = 1.3, p = 0.53), while the HOME score correlated with the DQ (r = 0.36, p = 0.02). In logistic regression analyses, the home environment was a greater determinant of risk for a low DQ than whether or not the mother attained metabolic control prior to prenancy (OR = 0.85, p = 0.02). These suggewst that treatment strategies addressing both prenatal and postnatal factors will most effectively reduce risks in maternal PKU.
Inherited defects of purine and pyrimidine metabolism: Laboratory methods for diagnosis
Authors: Duran M. , Dorland L. , Meuleman E. E. E. , Allers P. , Berger R. 
Published: December 2002

AbstractThe diagnosis of the majority of the known inherited defects of purine and pyrimidine metabolism can be achieved by analysing urinary excretion profiles. A quantitative measurement of the urinary uric acid/creatinine ratio should be the first approach for purine defects. The general screening system involves separation of the bases and nucleosides by reversed‐phase high‐performance liquid chromatography and multiwavelength UV detection. The catabolic defects of pyrimidine degradation can be diagnosed by gas chromatography ‐ mass spectrometry as used for organic acids. For the detection of adenylosuccinase deficiency, several simple but effective thin‐layer chromatographic methods are available.Techniques such as liquid chromatography ‐ mass spectrometry, direct nega‐tive‐ion fast‐atom bombardment mass spectrometry, and proton nuclear magnetic resonance spectroscopy give promising results, but are not yet being used on a large scale. Patients should keep to a simple diet and preferably be free of medication in order to allow a reliable interpretation of the analytical data.
Accumulation of sphingolipid activator proteins (SAPs) A and D in granular osmiophilic deposits in miniature Schnauzer dogs with ceroid‐lipofuscinosis
Authors: Palmer D. N. , Tyynelä J. , van Mil H. C. , Westlake V. J. , Jolly R. D. 
Published: December 2002

AbstractThe neuronal ceroid‐lipofuscinoses (NCL, Batten disease) are fatal inherited neurodegenerative diseases of children characterized by retinal and brain atrophy and the accumulation of electron‐dense storage bodies in cells. Mutations in different genes underlie different major forms. The infantile disease (CLN‐1, McKusick 256730) is distinguished by the storage of the sphingolipid activator proteins (SAPs) A and D in distinctive granular osmiophilic deposits (GRODs). This contrasts with the other major forms, where subunit c of mitochondrial ATP synthase is stored in various multilamellar profiles. Ceroid‐lipofuscinoses also occur in dogs, including a form in miniature Schnauzers with distinctive granular osmiophilic deposit‐like storage bodies. Antisera to SAPs A and D reacted to these storage bodies in situ. The presence of SAP D was confirmed by Western blotting and of SAP A by protein sequencing. Neither subunit c of mitochondrial ATP synthase nor of vacuolar ATPase is stored. This suggests that there are two families of ceroid‐lipofuscinoses, the subunit c‐storing forms, and those in which SAPs A and D, and perhaps other proteins, accumulate. Further work is required to determine whether other forms with granular osmiophilic deposits belong to the latter class and the genetic relationships between them and the human infantile disease.
Neurodevelopmental outcome of long‐term therapy of urea cycle disorders in Japan
Authors: Uchino T. , Endo F. , Matsuda I. 
Published: December 2002

AbstractIn Japan, urea cycle disorders (UCDs) are one of the most frequent inborn errors of metabolism, estimated to have a prevalence of 1 per 50 000 live births. In an attempt to develop more effective treatment and enhance the quality of life, we investigated the clinical manifestations and prognosis of 216 patients with UCDs diagnosed and treated between 1978 and 1995. These included 92 cases of neonatal‐onset UCD and 116 of late‐onset UCD. Two cases of ornithine transcarbamylase (OTC) deficiency in males and 2 cases of argininosuccinase (AL) deficiency were diagnosed prospectively. By far the most common disorder was OTC deficiency, accounting for 2/3 of all cases. At the end of 1995, the 5‐year survival rate was 22% for the neonatal‐onset type and 41% for the late‐onset type. Among the 20 long‐term survivors with neonatal‐onset UCD, 18 (90%) had moderate to severe neurodevelopmental deficits; this contrasts with 13 of 47 (28%) survivors with the late‐onset type. In analysing 108 UCD cases, peak blood ammonia level during the first hyperammonaemic attack was correlated with neurodevelopmental outcome. When the concentration of blood ammonia was less than 180 µmol/L (5 times normal), there was no severe neurological damage. When the concentration of blood ammonia exceeded 350 µmol/L (10 times normal) at the first hyperammonaemic attack, the patients died or had severe neurological deficits. Our data point to the importance of early diagnosis and aggressive treatment.
Does the polymorphism 677C‐T of the 5,10‐methylenetetrahydrofolate reductase gene contribute to homocysteine‐related vascular disease?
Authors: Thuillier L. , Chadefaux‐Vekemans B. , Bonnefont J. P. , Kara A. , Aupetit J. , Rochette C. , Montalescot G. , Couty M. C. , Kamoun P. , Ankri A. 
Published: December 2002

AbstractWhether the 677C‐T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene acts as a risk factor for homocysteine‐related vascular disease remains a matter of debate. Testing for the 677C‐T nucleotide substitution and assay of plasma homocysteine were carried out simultaneously in 69 controls and 113 vascular disease patients from the Paris area. The variant gene frequency as well as the variant homozygous genotype frequency were very similar in controls and patients. Conversely, plasma homocysteine levels were substantially higher in patients than in controls. A slight interaction between the 677C‐T MTHFR polymorphism and homocysteinaemia was observed in the patient group only, while a negative correlation between fasting homocysteine and plasma folate levels was found in all individuals homozygous for the 677C‐T MTHFR genotype, irrespective of vascular disease. These data suggest that the 677C‐T MTHFR polymorphism is not a major determinant of the vascular disease but contributes to increased plasma homocysteine concentration in conjunction with low plasma folate levels.