bluuebunny/crossref_metadata_2025_split huggingface dataset:
Riboflavin‐responsive defects of β‐oxidation
Authors: Gregersen N. 
Published: June 2005

AbstractThe key reaction in the β‐oxidation of fatty acids is the acyl‐CoA dehydrogenation, catalyzed by short chain, medium chain, and long chain acyl‐CoA dehydrogenases. Acyl‐CoA dehydrogenation reactions are also involved in the metabolism of the branched chain amino acids, where isovaleryl‐CoA and 2‐methylbutyryl‐CoA dehydrogenases are involved and in the metabolism of lysine, 5‐hydroxylysine and tryptophan, where glutaryl‐CoA dehydrogenase functions. In all of these dehydrogenation systems reducing equivalents are transported to the main respiratory chain by electron transfer flavoprotein (ETF) and electron transfer flavoprotein dehydrogenase (ETFDH), which are common to all the dehydrogenation systems. The acyl‐CoA dehydrogenation enzymes are dependent on flavin adenine dinucleotide (FAD) as coenzyme, for which riboflavin is the precursor. Patients with multiple acyl‐CoA dehydrogenation deficiencies have been found in whom the defect has been located to ETF and/or ETFDH. A few patients with multiple acyl‐CoA dehydrogenation deficiencies have been described, in whom no defects in acyl‐CoA dehydrogenases, ETF or ETFDH have been found but who respond clinically and biochemically to pharmacological doses of riboflavin. This indicates a defect related to the metabolism of FAD. An uptake defect of riboflavin or a synthesis defect of FAD from riboflavin have been excluded byin vivo andin vitro studies. A mitochondrial transport defect of FAD or a defect in the binding FAD to ETF and/or ETFDH remains possible.
Recent advances in the mechanism of pyridoxine‐responsive disorders
Authors: Fowler B. 
Published: June 2005

AbstractPyridoxine metabolism is summarised and speculation on possible defects leading to disease is made. Inherited deficiencies of PLP enzymes, which are known to respondin vivo to pharmacologic doses of pyridoxine are listed. The mechanism of pyridoxine responsiveness in homocystinuria due to cystathionine β‐synthase deficiency is discussed. There is a correlation in most (but not all) cases between the presence of residual CS activity, which is often stimulated by pyridoxal phosphate much more than control enzyme, in cultured fibroblasts and pyridoxine responsivenessin vivo. Exceptional patients have been found and are discussed in the light of more detailed studies on their cell lines. Clearly defined abnormalities of pyridoxal phosphate binding to mutant enzyme have been demonstrated and evidence of reduced intracellular stability of mutant CS and possible modulation by pyridoxal phosphate is presented. Preliminary findings suggest that the tissue level of pyridoxal phosphate achieved following pyridoxine treatment could be one other factor in determining pyridoxine responsiveness.
Vitamin E and muscle diseases
Authors: Jackson M. J. , Jones D. A. , Edwards R. H. T. 
Published: June 2005

AbstractStudies of the basic biochemical mechanisms underlying muscle damage aimed at finding agents which might reduce the amount of damage occurring in muscular dystrophy and other severe myopathies have been performed. These have suggested three types of agent which might be useful for this purpose, namely calcium antagonists, phospholipase inhibitors, and antioxidants or scavengers of reactive‐free radicals. Vitamin E falls into the latter of these three categories and has been shown to reduce the amount of damage which occurs in isolated skeletal muscles following a given stress. It is suggested that, in the absence of calcium antagonists having relatively specific and effective actions on skeletal muscle or suitable inhibitors of muscle phospholipases in man, therapy with vitamin E or other antioxidants may reduce the amount of muscle damage occurring in patients with severe myopathies.
Transport of carnitine into cells in hereditary carnitine deficiency
Authors: Eriksson B. O. , Gustafson B. , Lindstedt S. , Nordin I. 
Published: June 2005

SummaryCarnitine uptake has been studied in fibroblasts from a case of hereditary carnitine deficiency and in relatives. There was no evidence for carrier‐dependent uptake in cells from the patient. The mother and probably the healthy sister had an impaired uptake. The results show that the defect in this form of carnitine deficiency is an inability to establish a concentration gradient over the cell membrane.
Medium‐chain acyl‐CoA dehydrogenase deficiency: Metabolic effects and therapeutic efficacy of long‐terml‐carnitine supplementation
Authors: Treem W. R. , Stanley C. A. , Goodman S. I. 
Published: June 2005

SummaryMedium‐chain acyl‐CoA dehydrogenase deficiency is a recently described inborn error of metabolism characterized by episodes of coma and hypoketotic hypoglycaemia in response to prolonged fasting. Secondary carnitine deficiency has been documented in these patients as well as the excretion in the urine of medium‐chain‐length acyl carnitine esters, such as octanoylcarnitine. Based on the potential toxicity of medium‐chain fatty acid metabolites and the beneficial responses of patients with other inborn errors of metabolism and secondary carnitine deficiency, oral carnitine has been proposed as treatment for children with medium‐chain acyl‐CoA dehydrogenase deficiency. We report the results of carefully monitored fasting challenges of an infant with this deficiency both before and after 3 months of oral carnitine therapy. Carnitine supplementation failed to prevent lethargy, vomiting, hypoglycaemia and accumulation of free fatty acids in response to fasting despite normalization of plasma carnitine levels and a marked increase in urinary excretion of acyl‐carnitine esters. Potentially toxic medium‐chain fatty acids accumulated in the plasma in spite of therapy. Based on this study of one patient, we stress that avoidance of fasting and prompt institution of glucose supplementation in situations when oral intake is interrupted remain the mainstays of therapy for medium‐chain acyl‐CoA dehydrogenase deficient patients.
Evidence for inhibition of exodus of small neutral amino acids from non‐brain tissues in hyperphenylalaninaemic rats
Authors: de Cespedes C. , Thoene J. G. , Lowler K. , Christensen H. N. 
Published: June 2005

SummaryThe mechanism of the depletion of several plasma amino acids in PKU has remained unexplained. In the present study, a statistically significant decrease in the plasma concentration of several amino acids was observed 2 h after the intraperitoneal injection of Phe to weanling rats. The pattern was very similar to the one observed in PKU patients. Statistically significant increases in the distribution ratios liver/plasma and, mainly, muscle/plasma ratios accompanied in most of the cases the corresponding decreases in plasma concentrations. Equimolar injection under the same conditions of the non‐insulinogenic transport system L analogue, the a(±) isomer of the 2‐amino‐norbornane‐2‐carboxylic acid, produced, in a parallel effect to Phe, statistically significant increases in the distribution ratios of Ala and Gly, and probably of Pro in muscle, as well as of Ala in liver. These results seem to indicate that the high intracellular Phe attained inhibits the exodus of small neutral amino acids through system L, causing their depletion in plasma and ultimately in the brain. This effect may be additive to the inhibition by Phe of the entry of bulky neutral amino acids at the level of the blood‐brain barrier. Further study is needed to assess the relevance of these effects to PKU.
A case of pyruvate carboxylase deficiency with later prenatal diagnosis of an unaffected sibling
Authors: Tsuchiyama A. , Oyanagi K. , Hirano S. , Tachi N. , Sogawa H. , Wagatsuma K. , Nakao T. , Tsugawa S. , Kawamura Y. 
Published: June 2005

AbstractA severely mentally retarded infant with congenital lactic acidosis due to pyruvate carboxylase deficiency is reported. The patient suffered from vomiting and convulsions soon after birth and developed severe mental and motor retardation at 3 months of age.The persistent elevation of pyruvate and lactate in both blood and cerebrospinal fluid and hyperalanaemia suggested an impairment of pyruvate oxidation. The enzyme activities of pyruvate carboxylase in both liver tissues and cultured skin fibroblasts of the patient revealed values of about 5% of controls. However, pyruvate dehydrogenase and α‐ketoglutarate dehydrogenase activities in liver tissues were within normal limits.The patient had no response to administration of large doses of thiamine, lipoic acid and biotin, clinically and biochemically.A prenatal diagnosis was performed in the second pregnancy and the pyruvate carboxylase activities of the cultured amniotic fluid cells obtained by amniocentesis were within normal limits.
Introduction to recombinant DNA
Authors: Scott J. 
Published: June 2005

AbstractThis paper describes the current state of knowledge of methods for analysing gene structure and localization. Illustrations are given of the preparation of complementary DNA libraries and their screening by positive‐negative selection, the use of synthetic oligodeoxynucleotides and the use of antibodies. Analysis of the EGF precursor is used as an example to show its close relationship to plasma membrane receptor and its homology with the LDL receptor. Analysis of cloned genome DNA by use of bacteriophage lambda or cosmids gives useful information about gene regulation and evolution. Mutations by frame shift, point or missence mutations are discussed with reference to the LDL receptor and the apolipoproteins. The techniques of gene mapping by rat‐human cell hybridization and hybridizationin situ are illustrated, again with reference to genes coding for enzymes of cholesterol metabolism, the apolipoproteins and insulin‐like growth factors. Finally the potential ofin vitro mutagenesis and the injection of cloned DNA into the fertilized mouse ovum are discussed.
Human biochemical genetics of enzyme proteins in the new age of molecular genetics
Authors: Swallow D. M. , Hopkinson D. A. 
Published: June 2005

AbstractAdvances in protein biochemistry and immunology have had a major impact on the biochemical and genetical analysis of human proteins and have had applications in the analysis of the primary defects in metabolic disorders, as well as in cDNA cloning. The development and expansion of somatic cell genetic techniques has complemented conventional population and family study genetic methods. A large number of mammalian proteins undergo complex processing to achieve the synthesis of the biologically active protein. Much of this processing is under genetic control. Elucidation of these complexities requires a combination of biochemical, immunological and genetical approaches to determine the nature of the events involved.
Direct DNA analysis in family studies
Authors: Malcolm S. 
Published: June 2005

AbstractRestriction fragment length polymorphisms can be followed through families to track the incidence of genetic disease. Either cloned genes or anonymous DNA fragments, closely linked to the disease locus, may be used. 10 mL of blood collected into EDTA provide an excellent source of DNA and the blood is suitable for up to 3 days. In addition to gene tracking, the gene mutation itself may be studied to determine whether there is a DNA deletion.
Applications and limitations of direct DNA analysis in genetic prediction
Authors: Pembrey M. E. 
Published: June 2005

AbstractDirect analysis of DNA has enormous potential for improved carrier detection or exclusion and early prenatal diagnosis in monogenic diseases. The strategy adopted in practice is determined by the fact that in most diseases allelic genetic heterogeneity precludes elucidation of the mutation in all families. Gene tracking asks the question — has a relative or fetus inherited the same relevant chromosome region as a previously affected family member? — and requires a gene‐specific or closely linked DNA probe that reveals a restriction fragment length polymorphism (RFLP) in order to do a linkage study within the family. Gene tracking is independent of allelic heterogeneity in the disease, but is limited to those families in which key relatives are heterozygous for an RFLP.
Human DNA repair defects
Authors: Arlett C. F. 
Published: June 2005

AbstractA number of human genetic diseases have come to be described as being defective in DNA repair. The minimum criterion on which this assignment is based is hypersensitivity to the clastogenic or lethal action of specific DNA damaging agents. In one disease, xeroderma pigmentosum, the molecular evidence for a defect in DNA repair is unequivocal. This condition then acts as a model for dissecting others. For the other diseases the formal evidence for defects in repair is less secure or even lacking. The evidence for repair in each disease is assembled together with any methods that have been used to support the differential diagnosis or for prenatal diagnosis. Attempts to clone human DNA repair genes are in hand and may provide the necessary evidence to decide if all the putative DNA repair defective diseases are genuine.Neoplastic disease and neurological degeneration together with immune defects are frequent clinical features linking this set of diseases, suggesting that effective DNA repair may be important in many aspects of human health.
Molecular basis of α1‐antitrypsin deficiency and its potential therapy by gene transfer
Authors: Ledley F. D. , Woo S. L. C. 
Published: June 2005

AbstractThe gene for α1‐antitrypsin, a serum anti‐protease, has been cloned and sequenced. The underlying mutation in the PiZ allele has been identified as a G to A conversion giving rise to the substitution of glu by lys at position 342. Preparation of specific probes has allowed prenatal diagnosis. Recombinant retroviruses containing the normal human α1‐antitrypsin gene have been constructed and used to infect NIH3T3 cells. Analysis of DNA, RNA and protein indicate that successful incorporation of the α1‐antitrypsin was achieved and that the gene was capable of being expressed. The feasibility of genetic replacement therapy has been demonstrated and further experiments justified.
Diabetes mellitus, atherosclerosis, and the 5′ flanking polymorphism of the human insulin gene
Authors: Mandrup‐Poulsen T. , Owerbach D. , Nerup J. , Johansen K. , Hansen A. Tybjærg 
Published: June 2005

AbstractOn the 5′ side of the human insulin gene is a highly polymorphic locus containing 2 major size classes of DNA restriction fragments which segregate in families as stable genetic elements. Fragments with an average size of about 600 base‐pairs (bp) (the ‘L‐allele’) seem to be a weak genetic marker for type 1 (insulin‐dependent) diabetes mellitus, whereas fragments of an average size of about 2500 bp (the ‘U‐allele’) have hitherto been associated with type 2 (non‐insulin‐dependent) diabetes mellitus and diabetic hypertriglyceridaemia. Recent evidence does not confirm the association between the U‐allele and type 2 diabetes. Our own studies suggest that the U‐allele is a fairly strong marker for the development of atherosclerosis with a relative risk for U‐carriers of 3.36. The U‐allele has not been associated with conventional cardiovascular risk factors such as body weight, blood pressure, or levels of blood glucose, triglycerides or lipoproteins. The putative functions of the polymorphic region in the aetiology of type 1 diabetes and atherosclerosis, and the relation of this region to other genetic markers for these disorders are not known.
Clinical aspects of congenital adrenal hyperplasia: Early diagnosis and prognosis
Authors: Hughes I. A. 
Published: June 2005

AbstractThe neonatal presentation of congenital adrenal hyperplasia is either virilization of females or salt loss in both sexes. Early diagnosis is based on the rapid measurement of plasma 17α‐hydroxyprogesterone. Milder forms of congenital adrenal hyperplasia can present later in life with abnormalities of somatic or sexual development. The majority of cases of congenital adrenal hyperplasia are clinically diagnosable in the first 2–3 weeks of life: the need for screening for the remaining missed cases and the late onset types remains to be established.
Biochemical aspects of congenital adrenal hyperplasia
Authors: Honour J. 
Published: June 2005

AbstractThe assay of 17α‐hydroxyprogesterone in blood spots on filter paper forms the basis of neonatal screening programmes to detect congenital adrenal hyperplasia (CAH) due to 21‐hydroxylase deficiency. The blood concentrations of this hormone in the neonate varies with gestation age (termv preterm), age after birth, time of day and illness. Broad reference ranges for blood spot 17α‐hydroxyprogesterone concentrations are therefore quoted for healthy term infants and these ranges are not appropriate for the interpretation of values in preterm and sick newborns. There is a risk of a false‐negative or of a false‐positive diagnosis. Many of the above difficulties may result from variations in assay performance due to changes in the pattern of steroids produced by the adrenal gland which in turn relate to morphological changes in the adrenal cortex at this age. The purpose of this presentation is to define the complex steroid milieu of the newborn human and briefly to review the factors which determine the function of the adrenal gland, since these influence the extent to which an assay for this steroid needs to be evaluated before application to neonatal screening for CAH. The data to be presented derive from the capillary column gas chromatographic analysis (GC) of steroids in urine since this provides the best method to display the overall steroid production of the organism. The GC method has itself been refined so that CAH can now be reliably diagnosed using this method, but the information from this work will also be judged for its relevance to the problems encountered in the neonatal screening for CAH by blood spot analysis.
Responses of ground vegetation species to clear‐cutting in a boreal forest: aboveground biomass and nutrient contents during the first 7 years
Authors: Palviainen Marjo , Finér Leena , Mannerkoski Hannu , Piirainen Sirpa , Starr Michael 
Published: June 2005

AbstractRapid growth of ground vegetation following clear‐cutting is important to site productivity because vegetation retains nutrients in the ecosystem and can decrease nutrient leaching prior to stand re‐establishment. Aboveground biomass, nutrient contents (N, P, K and Ca) and species composition of ground vegetation were determined 1 year before and for 7 years after clear‐cutting of a mixed forest dominated by Norway spruce [Picea abies (L.) H. Karst.] in eastern Finland. The biomass of the feather mosses [Pleurozium schreberi Brid. and Hylocomium splendens (Hedw.) B. S.& G.] and the dwarf shrubs (Vaccinium myrtillus L. and V. vitis‐idaea L.), which had dominated the ground vegetation in the mature forest, significantly decreased after clear‐cutting. However, with the exception of H. splendens, these species had recovered within 3–5 years. The biomass of Deschampsia flexuosa (L.) Trin. considerably increased soon after clear‐cutting, and Epilobium angustifolium L. appeared 3–5 years after cutting. These species contributed to the retention of nutrients not simply because of their biomass but also because of higher nutrient concentrations in their tissues. Total biomass and nutrient contents of the ground vegetation exceeded those of the pre‐cutting levels. The proportion of ground vegetation biomass and nutrient contents represented by mosses decreased after cutting, while V. myrtillus, although reduced after cutting, remained a marked nutrient sink. The results suggest that H. splendens is the most sensitive species to cutting, but the biomass of P. schreberi, V. myrtillus and V. vitis‐idaea return to initial levels soon after clear‐cutting as do the nutrient contents of ground vegetation.
Microsites for seedling establishment of subalpine conifers in a forest with moss‐type undergrowth on Mt. Fuji, central Honshu, Japan
Authors: Sugita Hisashi , Nagaike Takuo 
Published: June 2005

AbstractWe examined microsites for the seedling establishment of Tsuga diversifolia, Abies veitchii and Abies mariesii in a subalpine coniferous forest with moss‐type undergrowth dominated by Hylocomium splendens and Pleurozium schreberi on Mt. Fuji, a less‐snowy mountain located on the Pacific Ocean side of the central part of Honshu Island, Japan, and compared these microsites with cases in other regions of Japan with different undergrowth vegetation (herb type, dwarf‐bamboo type) under snowier conditions. L‐shaped size structures with abundant seedlings and small trees were identified for all three species. Established seedlings of T. diversifolia showed remarkable preference for elevated microsites such as fallen logs and convex ground (i.e. ground raised around trunk bases), while A. veitchii and A. mariesii indicated no significant bias toward such elevated microsites in the large seedling stage. However, the relative frequency of T. diversifolia seedlings established on flat ground reached high values of 54–77%, since the relative occupation area of the flat ground was large (85–89%). Such a large share suggests that flat ground should be regarded as the most important microsite for the seedling establishment of T. diversifolia in forests with moss‐type undergrowth. This preference trait for T. diversifolia observed with moss‐type undergrowth has not been reported in previous studies examining forests with herb‐ and dwarf bamboo‐type undergrowth, where T. diversifolia seedlings are scarce on the ground and restricted to elevated microsites. We conclude that the major microsite for T. diversifolia seedling establishment changes according to the undergrowth vegetation type: a large ground share for moss‐type undergrowth and a small ground share for herb‐ and dwarf bamboo‐type undergrowth.
Comparison principle for second order elliptic operators and applications
Authors: Tahraoui Rabah 
Published: June 2005

Given two elliptic operatorsA_{1}andA_{2}, let us consider the following problems:\begin{cases} −A_{i}u_{i} = f_{i}, & f_{i}⩾0\text{ in }\Omega , \\ u_{i}|_{\partial _{\Omega }} = 0, & i = 1,2. \end{cases}In this work, we give some sufficient conditions ensuring the following comparison principle:u_{1}(x)⩾u_{2}(x)\:\forall x \in \Omega .As application, we study the behaviour, as|x|\rightarrow + \infty, of the solutionuof the problem\begin{cases} −Au = f\: &\text{in }\mathbb{R}^{N}, \\ \lim\limits_{|x|\rightarrow + \infty }u(x) = 0. & \end{cases}RésuméEtant donnés deux opérateurs\begin{cases} −A_{i}u_{i} = f_{i}, & f_{i}⩾0\text{ in }\Omega , \\ u_{i}|_{\partial _{\Omega }} = 0, & i = 1,2. \end{cases}Dans ce travail, on se propose de donner des conditions suffisantes portant surA_{i},f_{i}permettant de comparer les deux solutionsu_{1}etu_{2}:u_{1}(x)⩾u_{2}(x)\:\forall x \in \Omega .Comme application, nous étudions le comportement asymptotique, quand|x|\rightarrow + \infty, de la solutionudu problème suivant :\begin{cases} −Au = f\: &\text{in }\mathbb{R}^{N}, \\ \lim\limits_{|x|\rightarrow + \infty }u(x) = 0. & \end{cases}