bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glutaric aciduria type II: Biochemical investigation and treatment of a child diagnosed prenatally
Authors: Bennett M. J. , Curnock D. A. , Engel P. C. , Shaw L. , Gray R. G. F. , Hull D. , Patrick A. D. , Pollitt R. J. 
Published: June 2005

AbstractTwo sibs with the acute neonatal form of glutaric aciduria type II (deficientin vivo activity of multiple acyl‐CoA dehydrogenases) are described. In the second case diagnosis was made prenatally on the basis of reduced oxidation of palmitate by cultured amniotic fluid cells. With prompt intervention in the neonatal period and a carefully controlled diet later, this second case progressed well up to 4 months of age but died suddenly of cardiac failure, probably attributable to accumulation of fat. Neither patient showed any congenital morphological abnormality.Cultured fibroblasts from the second case showed a marked defect in the oxidation of a range of substrates requiring acyl‐CoA dehydrogenases for their catabolism, but residual activity for some substrates was quite high. Large quantities of sarcosine were excreted in urine, again suggesting that the mutation leaves some residual dehydrogenation activity. Butyryl‐, octanoyl‐ and palmitoyl‐CoA dehydrogenases were present in essentially normal quantities in postmortem liver.
Transport and storage of metals
Authors: Laurie S. H. 
Published: June 2005

AbstractCurrent understanding of the means by which the trace metals copper, iron and zinc are transported and stored in the human body is reviewed. Although metal‐related inherited metabolic diseases manifest themselves as deficiencies in metalloenzymes, these deficiencies in fact arise from disturbances in the absorption/rejection or transport or storage phases of the metal metabolism. The considerable information available on iron metabolism shows these phases to be closely interrelated with a number of feedback mechanisms operating as controls on the various metabolic stages. Copper and zinc have vastly different roles in their enzymes but, following their close coordination chemistry properties, have similar metabolic routes. Both make use of albumin for transport and of metallothionein at the absorption and hepatic‐binding stages. In contrast to iron, copper and zinc have no well‐defined storage system; instead they make use of body reserves distributed in various tissues. Our knowledge of the transport and storage systems of the trace metals is still very incomplete. More research is needed on the dynamics of movement of the trace metals between the various body tissues and fluids. Further advances will also come from the study of related metal inherited diseases in other animal species.
Mutations in humans and animals which affect copper metabolism
Authors: Camakaris J. , Phillips M. , Danks D. M. , Brown R. , Stevenson T. 
Published: June 2005

AbstractVarious inherited disorders of copper metabolism in man and animals are reviewed. Emphasis is placed on the use of cultured cells from mutants to determine the primary molecular defects and to acquire basic knowledge of normal copper metabolism. This allows better diagnostic tests and possible treatment of the disorders. Menkes' disease in humans and mottled mouse mutants are discussed in detail, as they illustrate these approaches.
Menkes' X‐linked disease: Prenatal diagnosis and carrier detection
Authors: Horn N. 
Published: June 2005

AbstractIncreased64Cu uptake into cultured cells is a biochemical marker for mutant cells in Menkes' disease (McKusick 30940). Using this marker selective prenatal diagnosis has been carried out in more than 80 at‐risk pregnancies. The64Cu uptake into cultures from affected male fetuses is, however, negatively correlated to the fetal age at amniocentesis. After the 18th week of gestation the risk of false negatives is significant.Using copper uptake into uncloned cultures, a number of obligate and possible carriers showed significantly increased values, but the range of values of obligate carriers considerably overlapped those of the normal controls. All values of normal controls were within a limited range and values above the upper limit in females at risk must, therefore, be caused by mutant cells and establish the carrier diagnosis. However, the extreme skewing of the distribution towards normal values in obligate carriers indicates a strong selection against the mutant cell type and this will hamper the detection of all female carriers in risk families.C‐banding heteromorphism of the X‐chromosome provides a supplementary carrier detection method. Linkage analysis in five Danish families demonstrated a close physical relationship between the gene for Menkes' disease and the centromere region. By comparative gene mapping (mouse/man) the most likely localization of the gene for Menkes' disease can be suggested to be in band q13 on the long arm of the human X‐chromosome. This regional assignment facilitates the choice of appropriate X‐specific DNA probes in search for linkage at the DNA level.
Inborn errors of cellular organelles: an overview
Authors: Tager J. M. 
Published: June 2005

AbstractMetabolic processes in the cell are catalysed by enzymes and enzyme systems present in discrete intracellular compartments consisting of the cytosol and various intracellular organelles. Three well defined groups of genetic diseases in man can now be recognized in which the functions of an intracellular organelle are impaired: lysosomal storage diseases, mitochondrial disorders and peroxisomal diseases. Extensive studies carried out during the last decade on the biogenesis of intracellular organelles have contributed to an understanding of the molecular basis of the lesions leading to these three groups of genetic disorders. The results of the studies have stressed that such lesions can arise not only through mutations in the structural genes for the proteins in an organelle but also through mutations in the genes coding for components required for the specific transport and incorporation of proteins into organelles.
Effects of phenylalanine loading on protein synthesis in the fetal heart and brain of rat: an experimental approach to maternal phenylketonuria
Authors: Okano Y. , Chow I. Z. , Isshiki G. , Inoue A. , Oura T. 
Published: June 2005

AbstractPregnant rats were loaded withl‐phenylalanine, and the distributions of [14C]leucine and [14C]urea into fetal plasma and tissues were examined. Uptake of [14C]leucine into the supernatant and protein fractions of fetal plasma and tissues was low in the rats loaded with phenylalanine. In contrast, [14C]urea was distributed identically in both groups, indicating that maternal hyperphenylalaninemia did not affect blood flow across the placenta. Administration of phenylalanine andp‐chlorophenylalanine produced amino acid imbalance in fetal tissues. Along with these changes, polysomes of the affected fetal heart and brain disaggregated without changes in the ribonuclease activity. These results indicate that high phenylalanine levels in maternal plasma disturb the active transport of amino acids across the placenta, causing an amino acid imbalance and disaggregation of polysomes in fetal heart and brain. These changes may contribute to the congenital heart disease and mental retardation of maternal phenylketonuria.
Possible prenatal diagnosis of type III glycogenosis
Authors: Maire I. , Mathieu M. 
Published: June 2005

AbstractThis paper reports the first prenatal diagnosis in a pregnancy at risk for type III glycogenosis using a reliable test for amylo‐1,6‐glucosidase in cultured amniotic fluid cells. This test, based upon the different rates of glycogen and phosphorylase limit dextrin hydrolysis, was found to be more reliable in detecting a deficiency of amylo‐1,6‐glucosidase activity than either phosphorylase limit dextrin hydrolysis alone or [14C]glucose incorporation using leukocytes and cultured cells.
Amniotic tissue transplantation as a trial of treatment in some lysosomal storage diseases
Authors: Tylki‐Szymańska A. , Maciejko D. , Kidawa M. , Jabłońska‐Budaj U. , Czartoryska B. 
Published: June 2005

AbstractThis communication reports the clinical and biochemical results in six patients: four with mucopolysaccharidosis, one with GM1 gangliosidosis (Morquio B) and one with I‐cell disease, who were treated by amniotic tissue transplantation. The sole evident clinical result was the diminishing of corneal clouding in three cases. A slight increase of beta‐galactosidase activity in one patient's plasma was observed. The time of improvement was about 2 months after the transplantation and was transitory.
Cranial computerized tomography in dihydropteridine reductase deficiency
Authors: Longhi R. , Valsasina R. , Buttè C. , Paccanelli S. , Riva E. , Giovannini M. 
Published: June 2005

AbstractDihydropteridine reductase deficiency is a rare cause of hyperphenylalaninaemia, characterized by severe and progressive neurological impairment, despite early and accurate dietary control of plasma phenylalanine. We describe two girls, diagnosed at 17 and 14 months of age, respectively, and immediately treated withl‐dopa, 5‐hydroxytryptophan and carbidopa. In spite of an adequate dietary and pharmacological treatment, the clinical and neurological pictures progressively worsened. Repeated cranial computerized axial tomography scans showed degeneration of the white matter and, in one case, calcification of the basal ganglia. The possible association of this last finding with folate depletion is discussed.
Biochemical phenotyping of a single sibship with both cystinosis and fabry disease
Authors: Gahl W. A. , Adamson M. , Kaiser‐Kupfer I. , Ludwig I. H. , O'Connell H. J. , Cohen W. , Barranger J. 
Published: June 2005

AbstractTwo lysosomal storage diseases, cystinosis and Fabry disease, were diagnosed clinically in different members of a single sibship. The possibility that the affected sister and brother might have related disorders with disparate manifestations was pursued. The four principal family members were tested for heterozygote status with respect to serum and leukocyte α‐galactosidase A activity, urinary trihexosylceramide excretion, and the capacity to engage in cystine counter‐transport across leukocyte lysosome membranes. Results were consistent with classical autosomal recessive inheritance in the case of cystinosis and X‐linked inheritance for Fabry disease, confirming that this family represents an example of two rare disorders occurring in the same sibship.
An evaluation of protein requirements in methylmalonic acidaemia
Authors: Ney D. , Bay C. , Saudubray J. M. , Kelts D. G. , Kulovich S. , Sweetman L. , Nyhan W. L. 
Published: June 2005

AbstractA 3‐month‐old girl and a 13‐month‐old boy with vitamin B12‐unresponsive methylmalonic acidaemia were studied to determine responses to varying levels of protein intake of growth, nitrogen balance and organic acid metabolism. A linear increase in the excretion of methylmalonic acid was observed in both patients above a critical level of protein intake. The inflection point was judged to reflect a ceiling above which amino acid intake exceeded requirements and catabolism was initiated. Below this point in each infant there was a plateau of minimal excretion of methylmalonic acid. Within this plateau level a reasonable rate of growth and metabolic stability were achieved at intakes between 0.70 and 0.75 and between 0.75 and 1.17 g protein kg−1, respectively, indicating that there is a range of protein tolerance and the importance of an individual approach to the provision of protein in patients with methylmalonic acidaemia. In the 3‐month‐old infant, nitrogen equilibrium was achieved at protein intakes above 0.6 g kg−1 and modest nitrogen retention was attained at a protein intake of 0.75 g kg−1, a level at which the excretion of methylmalonic acid was minimal and weight gain satisfactory. A protein intake of 1.25 g kg−1 was required to achieve a level of nitrogen retention often considered optimal for normal growth; however, this infant demonstrated an elevated excretion of methylmalonic acid and was close to clinical illness at this level of protein intake. The 13‐month‐old infant demonstrated a normal level of nitrogen retention, minimal excretion of methylmalonic acid, and a satisfactory rate of growth at protein intakes of 1.0–1.17 g kg−1. The values should prove useful guidelines for the management of infants requiring minimal intakes of protein. In studies carried out at 18–20 months of age, supplementation of the basic diet containing 0.75 g kg protein−1 with a mixture of amino acids not containing the precursors of methylmalonic acid was associated with increase of retention of nitrogen and increased concentrations of some essential amino acids in plasma, but effects on growth and the excretion of methylmalonic acid were not significant.
Groin Hernia Repair by Laparoscopic Techniques: Current Status and Controversies
Authors: Arregui Maurice E. , Young Susan B. 
Published: June 2005

AbstractLaparoscopic hernia repair remains controversial, and its position in current hernia surgery remains in flux. In this article we attempt to put the laparoscopic approach in perspective by describing the rationale for its development. We summarize studies comparing it with open repairs, including recent publications, meta‐analyses, and systematic reviews; and we then contrast the data with recent findings of the United States Veterans Affairs Cooperative study 456. We discuss the current and future status of the laparoscopic approach to inguinal hernia repair and present an update of our own laparoscopic totally extraperitoneal technique without mesh fixation. From 1994 to 2004 we performed 314 hernia repairs on 224 patients with no intraoperative complications, no conversions to an open procedure, and no mortality. Thirty (14%) minor postoperative complications occurred. There were three herniated lipomas (preperitoneal fat) but no true peritoneal reherniations. We evaluate critical points of laparoscopic hernia repair including extensive preperitoneal dissection, mesh configuration, size and fixation, cost reduction, and the learning curve.
Species richness and composition of Curculionidae (Coleoptera) in a conifer plantation, secondary forest, and old‐growth forest in the central mountainous region of Japan
Authors: Ohsawa Masashi 
Published: June 2005

AbstractWeevil (Curculionidae, Coleoptera) species richness and composition were investigated and compared among larch [Larix kaempferi (Lamb.) Carriére] plantations, secondary forests, and old‐growth forests in the central mountainous region of Japan. In addition, to assess the effects of forest‐management practices, namely thinning and long‐rotation logging schedules (long rotation), the weevil assemblages of recently thinned middle‐aged and long‐rotated larch plantations were compared with those of middle‐aged larch plantations. Malaise traps were set in 44 stands of these forest types, and weevils were separated and identified. Several environmental factors other than forest type were also examined. Weevil species richness and diversity indices [Shannon‐Wiener diversity index (H′) and Simpson's index of diversity (D)] were higher in the secondary forest than in the larch plantation. Because of its wide distribution and higher weevil species richness, the secondary forest contributed to maintaining weevil diversity in this region. Old‐growth forest had higher diversity indices (H′ and D) than did the larch plantation. The secondary forest had the highest number of species in total. Though the number of individuals was the highest in larch plantation, species richness, H′ and D of the plantation were generally low. Weevil community structure and species composition differed among the three forest types, but the difference in weevil composition between the larch plantation and the other two forest types was the largest. Forest type is probably the most important factor for determining the differences in weevil assemblage, and further, both dominant tree type (coniferous trees versus broad‐leaved trees) and the number of mature tree species seem to be important factors for weevil species composition. Among forest management practices, long rotation caused diversity indices (H′ and D) to increase while thinning appeared to cause only minor changes in the weevil assemblages. Because species richness and species composition of Curculionidae well reflected the differences in forest types and some other environmental factors investigated, this family seems suitable for diversity research in forests. Further research on biodiversity with the use of this family should, therefore, be expected.
Summer mesozooplankton distribution in coastal waters of central Greece (eastern Mediterranean). I. Hydrology and group composition
Authors: Ramfos Alexis , Somarakis Stylianos , Koutsikopoulos Constantin , Fragopoulu Nina 
Published: June 2005

Zooplankton and hydrography of the upper 200 m was studied in coastal and pelagic waters off central Greece (eastern Mediterranean) during July 1998. The spatial distribution of the main environmental (temperature, salinity, fluorescence) and zooplankton (abundance, dry-weight, dominant groups) features of the area was delimited over an intense grid of 124 stations. The complex topography of the surveyed area comprised an interesting field for the study of pelagic–coastal interaction and its influence on the taxonomic composition of zooplankton.A typical summer thermal stratification was observed over the entire study area. Marked differences were found in surface-salinity between the eastern (Aegean Sea) and the western (Ionian Sea) part of the study area, which was attributed to the presence of less saline waters originating from the Black Sea. A deep fluorescence maximum was present in both coastal and pelagic stations. Zooplankton abundance and biomass showed an inshore–offshore gradient with coastal areas being significantly richer than pelagic areas. The taxonomic composition of zooplankton varied greatly both along the inshore–offshore gradient and among the different semi-enclosed Gulfs. Copepods were the dominant group in the pelagic waters comprising 67–78% in terms of mean relative abundance. In coastal areas, copepods were less important with cladocerans (especially the species Penilia avirostris) being the dominant group (44–51%). Appendicularians and chaetognaths comprised an important component of the zooplankton community over the entire surveyed area with mean relative abundance ranging from 2·5 to 14% and 0·6 to 5·8%, respectively.
The Quintiles Prize Lecture 2004: The identification of the adenosine A2B receptor as a novel therapeutic target in asthma
Authors: Holgate Stephen T 
Published: June 2005

Adenosine is a powerful bronchoconstrictor of asthmatic, but not normal, airways. In vitro studies on isolated human mast cells and basophils revealed that adenosine and selective analogues augmented inflammatory mediator release from mast cells by stimulating A2 receptors. Pharmacological blockade of mast cell mediator release in vivo also attenuated adenosine‐induced bronchoconstriction, as did theophylline, by adenosine A2 receptor antagonism. Further in vitro studies revealed that the asthmatic response to adenosine is likely to be mediated via the A2B subtype which is selectively antagonised by enprofylline. Studies in animal models, especially mice, have shown a close synergistic interaction between adenosine, Th2 and airway remodelling responses. The recent description of A2B receptors on human airway smooth muscle cells that mediate cytokine and chemokine release and induce differentiation of fibroblasts into myofibroblasts strengthens the view that adenosine maybe more than an inflammatory mediator in asthma but also participates in airway wall remodelling in this disease. These data have provided a firm basis for developing adenosine A2B receptor antagonists as a new therapeutic approach to this disease.British Journal of Pharmacology (2005) 145, 1009–1015. doi:10.1038/sj.bjp.0706272
Somatostatin at nanomolar concentration reduces collagen I and III synthesis by, but not proliferation of activated rat hepatic stellate cells
Authors: Reynaert Hendrik , Rombouts Krista , Jia Yutao , Urbain Daniel , Chatterjee Nirjhar , Uyama Naoki , Geerts Albert 
Published: June 2005

Previous studies have shown antifibrotic effects of somatostatin. Since hepatic stellate cells (HSC) express somatostatin receptors and play a key role in hepatic fibrogenesis, we investigated the in vitro antifibrotic effect of somatostatin on rat HSC.
At day 12 after isolation, cells were exposed to different concentrations of somatostatin (10−6–10−9 mol l−1).
mRNA expression of collagen types I and III, and of smooth muscle α‐actin (α‐SMA) was analysed by Northern blotting. At 10−9 mol l−1, somatostatin significantly reduced mRNA expression of collagen I (72.3±10.7%; 95% confidence interval (95% CI): 45.5–99.0), collagen III (79.0±4.5%; 95% CI: 67.6–90.4) and α‐SMA (65.7±5.9%; 95% CI: 51.1–80.2), as compared to control normalized at 100%. These results were confirmed by quantitative RT–PCR.
Cycloheximide experiments indicated that somatostatin has no direct transcriptional effect.
Using immunoprecipitation, we demonstrated that somatostatin also decreased de novo synthesis of collagen I (73±10%; 95% CI: 48–98%), collagen III (65±13%; 95% CI: 33–97%) and α‐SMA (47±9%; 95% CI: 25–69%). Remarkably, at higher concentrations, somatostatin did not suppress collagen mRNA expression nor de novo protein synthesis. We ascribe this observation to desensitization of the cells for somatostatin.
Cell proliferation, as measured by 5‐bromo‐2′‐deoxyuridine labelling, was not altered by somatostatin.
No significant effect on the intermediate and actin cytoskeleton were detected by immunohistochemistry and Western blotting.
Our findings imply that in vivo antifibrotic effects of somatostatin could result partially from a direct action of somatostatin on HSC, but other, in vivo effects are probably also involved.

British Journal of Pharmacology (2005) 146, 77–88. doi:10.1038/sj.bjp.0706298