bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tetrahydrobiopterin deficiency and dopamine loss in a genetic mouse model of Lesch‐Nyhan disease
Authors: Hyland K. , Kasim S. , Egami K. , Arnold L. A. , Jinnah H. A. 
Published: May 2004

AbstractSummary: Hypoxanthine‐guanine phosphoribosyltransferase (HPRT) is an enzyme that catalyses the conversion of hypoxanthine and guanine into their respective nucleotides. Inherited deficiency of the enzyme is associated with a loss of striatal dopamine in both mouse and man. Although HPRT is not directly involved in the metabolism of dopamine, it contributes to the supply of GTP, which is used in the first and rate‐limiting step in the synthesis of tetrahydrobiopterin (BH4). Since BH4 is required as a cofactor for tyrosine hydroxylase in the synthesis of dopamine, any limitation in the supply of GTP could interfere with the synthesis of dopamine. The current studies were designed to address the hypothesis that the reduced striatal dopamine in mice with HPRT deficiency results from reduced availability of BH4. The mutant mice had small reductions in striatal BH4, with normal BH4 levels in other brain regions. Liver BH4 was normal in HPRT‐deficient mutant mice, and a phenylalanine challenge test failed to reveal any evidence for impaired hepatic phenylalanine hydroxylase, another BH4‐dependent enzyme. Although striatal BH4 content is not normal, supplementation with BH4 or L‐dopa failed to correct the striatal dopamine deficiency of the mutant mice, suggesting that BH4 limitation is not responsible for the dopamine loss.
Maternal histidinaemia: Pregnancies and offspring outcomes
Authors: Levy H. L. , Yu J. J. , Waisbren S. E. 
Published: May 2004

AbstractSummary: Untreated pregnancies and their outcomes were studied in 10 women with histidinaemia and their 26 pregnancies. The mean maternal assigned histidine level was 727±186 µmol/L (range 484–1053). Six women had classic histidinaemia (assigned level>700 µmol/L) and the remaining four had mild (atypical) histidinaemia. The pregnancies were uneventful, with only one spontaneous loss and 25 live births. Birth measurements were normal and no congenital anomalies were observed. Growth and development were normal in all offspring. IQ among the 23 offspring tested was 103±12 (range 79–122). Four offspring required special education for brief periods and one for several years, but this frequency, as well as that of 12% for attention deficit hyperactive disorder, was not significantly different from expected in the general population. It would appear that maternal histidinaemia, unlike maternal phenylketonuria, can be added to the list of maternal inborn errors of metabolism that are nonteratogenic.
A new, low‐volume protein substitute for teenagers and adults with phenylketonuria
Authors: MacDonald A. , Lilburn M. , Cochrane B. , Davies P. , Daly A. , Asplin D. , Hall S. K. , Cousins A. , Chakrapani A. , Robinson P. , Lee P. 
Published: May 2004

AbstractSummary: Some older patients with phenylketonuria (PKU) fail to consume their protein substitute (with or without vitamin and mineral supplements) in prescribed amounts, which contributes to poor blood phenylalanine control. PKU Express (Vitaflo), is a new low‐volume (amino acids 72 g/100 g), low‐carbohydrate, phenylalanine‐free protein substitute with added vitamins and minerals designed for people with PKU over 8 years of age. In an open intervention study, the aim was to investigate its acceptability and effectiveness in a group of teenagers and adults with PKU. Twenty‐three subjects (15 female; 8 male) with PKU, who had a median age of 17 years (range 8–37 years) took the substitute for 8weeks. A 3‐day prospective diet diary, height, weight, plasma amino acids, biochemical and haematological nutritional analytes were measured at weeks 0 and 8. Skin‐puncture bloods for plasma phenylalanine were collected every 2 weeks. The median weight of protein substitute (with or without vitamin and mineral supplements) consumed decreased by 33% from 150 g (range 140–180) daily to 100 g (range 100–125) daily (p<0.001). Median change in energy intake decreased by a median of 10% (95% CI 2.0 to 18.0) when compared to intake on original protein substitute. On PKU Express, the intakes of all nutrients exceeded the dietary reference values but none was excessively high. Blood phenylalanine decreased by a mean of 37 µmol/L (95% CI‐27 to 102) during the trial. Body mass index decreased in 40% of subjects. Changes in blood phenylalanine or body mass index were not statistically significant. Most of the nutritional, haematological and biochemical indices stayed within normal reference ranges for the analytes studied. Sixteen (70%) of the subjects had low plasma selenium at the start, but only 13 (57%) at the study end. Plasma vitamin B12 was high in 8 subjects at the start of the study and 9 at the end. Twenty‐one subjects (96%) stated that the product was convenient and easy to prepare. However, 7 (32%) described the smell and 9 (46%) the texture as the same as or worse than those of previous protein substitutes. Because of the use of the premeasured sachets, some subjects were able to prepare their own protein substitute for the first time. PKU Express is a safe, efficacious, protein substitute that significantly reduces the daily volume of prescribed protein substitute.
The early‐onset phenotype of mitochondrial trifunctional protein deficiency: A lethal disorder with multiple tissue involvement
Authors: Spiekerkoetter U. , Khuchua Z. , Yue Z. , Strauss A. W. 
Published: May 2004

AbstractSummary: Mitochondrial trifunctional protein (TFP) deficiency is a clinically heterogeneous disorder with phenotypes of different severity. Early‐onset, severe forms predominantly exhibit cardiomyopathy, life‐threatening arrhythmias and liver dysfunction; the later‐onset, milder phenotype is mainly characterized by neuromyopathic features. The mechanisms that determine these heterogeneous presentations are unknown. We performed multiple tissue immunoblots from a patient with early‐onset, lethal TFP deficiency and demonstrated absent TFP antigen in all. The predominant cardiac manifestation of severe TFP deficiency reflects its essential role in myocardial energetics, not its tissue‐specific expression.
Sedation with 4‐hydroxybutyric acid: A potential pitfall in the diagnosis of SSADH deficiency
Authors: Wolf N. I. , Haas D. , Hoffmann G. F. , Jakobs C. , Salomons G. S. , Wevers R. A. , Engelke U. F. , Rating D. 
Published: May 2004

AbstractSummary: Deficiency of succinic semialdehyde dehydrogenase (SSADH) is a rare neurometabolic disorder with accumulation of 4‐hydroxybutyric acid (4‐HBA) as a biochemical hallmark. We present a boy with an unresolved severe neurological disorder and intermittent elevation of 4‐HBA in serum and CSF which was later shown to result from iatrogenic administration of 4‐HBA for sedation purposes.
Glutathione synthetase deficiency associated with antenatal cerebral bleeding
Authors: Brüggemann L. W. , Groenendaal F. , Ristoff E. , Larsson A. , Duran M. , van Lier J. A. C. , Dorland L. , Berger R. , de Koning T. J. 
Published: May 2004

AbstractSummary: We present a newborn with glutathione synthetase deficiency and intracranial haemorrhages. Because the latter are rare in term newborns a possible relationship with glutathione synthetase deficiency will be discussed.
Dynamics and mediators of acute graft attrition after myoblast transplantation to the heart
Authors: Suzuki Ken , Murtuza Bari , Beauchamp Jonathan R. , Smolenski Ryszard T. , Varela‐Carver Anabel , Fukushima Satuki , Coppen Steven R. , Partridge Terence A. , Yacoub Magdi H. 
Published: May 2004

ABSTRACTSurvival and proliferation of skeletal myoblasts within the cardiac environment are crucial to the therapeutic efficacy of myoblast transplantation to the heart. We have analyzed the early dynamics of myoblasts implanted into the myocardium and investigated the mechanisms underlying graft attrition. At 10 min after implantation of [14C]thymidine‐labeled male myoblasts into female mice hearts, 14C measurement showed that 39.2 ± 3.0% of the grafted cells survived, and this steadily decreased to 16.0 ± 1.7% by 24 h and to 7.4 ± 0.9% by 72 h. PCR of male‐ specific Smcy gene calculated that the total (surviving plus proliferated) number of donor‐derived cells was 18.3 ± 1.6 and 23.3 ± 1.3% at 24 and 72 h, respectively, indicating that proliferation of the surviving cells began after 24 h. Acute inflammation became prominent by 24 h and was reduced by 72 h as indicated by myeloperoxidase activity and histological findings. Multiplex RT‐PCR revealed corresponding changes in IL‐1β, TGF‐β, IL‐6, and TNF‐α expression. Treatment with CuZn‐superoxide dismutase attenuated the initial rapid death and resulted in enhanced cell numbers afterward, giving a twofold increased total number at 72 h compared with the nontreatment. This effect was associated with reduced inflammatory response, suggesting a causative role for superoxide in the initial rapid graft death and subsequent inflammation. These data describe the early dynamics of myoblasts implanted into the myocardium and suggest that initial oxidative stress and following inflammatory response may be important mechanisms contributing to acute graft attrition, both of which could be potential therapeutic targets to improve the efficiency of cell transplantation to the heart.
IL‐13 and IL‐1β promote lung fibroblast growth through coordinated up‐regulation of PDGF‐AA and PDGF‐Rα
Authors: Ingram Jennifer L. , Rice Annette B. , Geisenhoffer Kristen , Madtes David K. , Bonner James C. 
Published: May 2004

ABSTRACTPeribronchiolar fibrosis is a prominent feature of airway remodeling in asthma and involves fibroblast growth and collagen deposition. Interleukin‐13 (IL‐13), a T‐helper 2 cytokine, is a key mediator of airway remodeling in asthma, yet the mechanism through which IL‐13 promotes fibroblast growth has not been investigated. In this study, we show that IL‐13 stimulates the mitogenesis of mouse, rat, and human lung fibroblasts through release of a soluble mitogen that we identified as PDGF‐AA. The IL‐13‐induced growth of human lung fibroblasts was attenuated by an anti‐PDGF‐AA neutralizing antibody, and IL‐13 stimulated human lung fibroblasts to secrete PDGF‐AA. Fibroblasts derived from mouse embryos possessing the lethal Patch mutation, which lack the PDGF‐Rα, showed no mitogenic response to IL‐13. However, Patch cells did exhibit IL‐13‐induced STAT‐6 phosphorylation. Stable transfection of the PDGF‐Rα into Patch cells restored the growth response to PDGF‐AA and IL‐13. Through the use of lung fibroblasts from STAT‐6‐deficient mice, we showed that IL‐13‐induced PDGF‐AA release is STAT‐6 dependent, but PDGF‐AA‐induced growth is STAT‐6 independent. Finally, we showed that IL‐1β enhanced IL‐13‐induced mitogenesis of rat lung fibroblasts through up‐regulation of the PDGF‐Rα. Our findings indicate that IL‐13 acts in synergy with IL‐1β to stimulate growth by coordinately up‐regulating PDGF‐AA and the PDGF‐Rα, respectively.
Hydrogen sulfide protects neurons from oxidative stress
Authors: Kimura Yuka , Kimura Hideo 
Published: May 2004

ABSTRACTHydrogen sulfide (H2S), which is a well‐known toxic gas, is found in relatively high concentrations in the brain. Although a neuromodulatory role of H2S has been demonstrated, little is known of its other biological functions. Here we show that H2S protects primary cultures of neurons from death in a well‐studied model of oxidative stress caused by glutamate, a process called oxidative glutamate toxicity—or oxytosis. We found that H2S increases the glutathione levels, which normally decrease during the cell death cascade, by enhancing the activity of γ‐ glutamylcysteine synthetase and up‐regulating cystine transport. Cystine (cysteine) is the rate‐ limiting substrate of glutathione synthesis. These observations reveal that H2S protects neurons from oxytosis by increasing the production of the antioxidant glutathione.
Pseudoaneurysms of the Superficial Temporal Artery: Treatment Options
Authors: Isaacson Glenn , Kochan Polly S. , Kochan Jeffrey P. 
Published: May 2004

AbstractObjectives: Pseudoaneurysms of the superficial temporal artery present as slowly growing masses of the face or scalp. They may arise as a result of infection or autoimmune disease but most commonly are sequelae of blunt, penetrating, or surgical trauma. We describe their clinical presentation and differential diagnosis and compare several treatment options.Study Design: Observational case series.Methods: We retrospectively reviewed the presentations, diagnostic evaluations, and management in three young men who presented with pseudoaneurysms after trauma. A computerized review of the world's literature revealed a variety of methods for the control of head and neck pseudoaneurysms.Results: Surgical resection, ligation without resection, intravascular sclerosis, and coil embolization have all been used to treat these lesions. We treated two lesions by coil embolization and one by surgical resection. Long‐term control was achieved in each case.Conclusions: Surgical resection cures pseudoaneurysms in most cases. The frontal and zygomatic branches of the facial nerve are at risk during this procedure. Local sclerosis is effective but may cause distal tissue necrosis. Coil embolization is highly effective and leaves no facial scar but carries small risks of stroke, lower extremity ischemia, and groin pseudoaneurysm.
A New Classification System for Congenital Laryngeal Cysts
Authors: Forte Vito , Fuoco Gabriel , James Adrian 
Published: May 2004

AbstractObjectives: A new classification system for congenital laryngeal cysts based on the extent of the cyst and on the embryologic tissue of origin is proposed.Study Design: Retrospective chart review.Methods: The charts of 20 patients with either congenital or acquired laryngeal cysts that were treated surgically between 1987 and 2002 at the Hospital for Sick Children, Toronto were retrospectively reviewed. Clinical presentation, radiologic findings, surgical management, histopathology, and outcome were recorded. A new classification system is proposed to better appreciate the origin of these cysts and to guide in their successful surgical management.Results: Fourteen of the supraglottic and subglottic simple mucous retention cysts posed no diagnostic or therapeutic challenge and were treated successfully by a single endoscopic excision or marsupialization. The remaining six patients with congenital cysts in the study were deemed more complex, and all required open surgical procedures for cure. On the basis of the analysis of the data of these patients, a new classification of congenital laryngeal cysts is proposed. Type I cysts are confined to the larynx, the cyst wall composed of endodermal elements only, and can be managed endoscopically. Type II cysts extend beyond the confines of the larynx and require an external approach. The Type II cysts are further subclassified histologically on the basis of the embryologic tissue of origin: IIa, composed of endoderm only and IIb, containing endodermal and mesodermal elements (epithelium and cartilage) in the wall of the cyst.Conclusions: A new classification system for congenital laryngeal cysts is proposed on the basis of the extent of the cyst and the embryologic tissue of origin. This classification can help guide the surgeon with initial management and help us better understand the origin of these cysts.
Relics of Davy and Faraday in New Zealand
Authors: Tee G. J. 
Published: May 2004

In April 1997 Sir John Meurig Thomas, F.R.S., toured New Zealand, as the 1997 Rutherford Lecturer of the Royal Society of London. He delivered his Rutherford Lecture on Sir Humphry Davy, P.R.S. (1778–1829), and Michael Faraday, F.R.S. (1791–1867), the first and second Directors of the Royal Institution.
Many place–names in New Zealand commemorate scientists. There is Mount Davy (1012 m) at 42°23'S, 171°23'E, between Greymouth and Blackball. Mount Faraday, at 42°03'S, 171°30'E, is the highest peak (1485 m) in the Paparoa Range (south of Westport), whose successive peaks from south to north are named Mounts Lodge, Ramsay, Dewar, Priestly, Faraday, Curie, Einstein, Euclid and Kelvin. And Mount Copernicus and Mount Galileo are 10 km east of the Paparoa Range.
Alx4 and Msx2 play phenotypically similar and additive roles in skull vault differentiation
Authors: Antonopoulou Ileana , Mavrogiannis Lampros A. , Wilkie Andrew O. M. , Morriss‐Kay Gillian M. 
Published: May 2004

Abstract Alx4 and Msx2 encode homeodomain‐containing transcription factors that show a clear functional overlap. In both mice and humans, loss of function of either gene is associated with ossification defects of the skull vault, although the major effect is on the frontal bones in mice and the parietal bones in humans. This study was undertaken to discover whether Alx4 and Msx2 show a genetic interaction in skull vault ossification, and to test the hypothesis that they interact with the pathway that includes the Fgfr genes, Twist1 and Runx2. We generated Alx4+/–/Msx2+/– double heterozygous mutant mice, interbred them to produce compound genotypes and analysed the genotype–phenotype relationships. Loss of an increasing number of alleles correlated with an incremental exacerbation of the skull vault defect; loss of Alx4 function had a marginally greater effect than loss of Msx2 and also affected skull thickness. In situ hybridization showed that Alx4 and Msx2 are expressed in the cranial skeletogenic mesenchyme and in the growing calvarial bones. Studies of the coronal suture region at embyonic day (E)16.5 revealed that Alx4 expression was decreased, but not abolished, in Msx2−/– mutants, and vice versa; expression of Fgfr2 and Fgfr1, but not Twist1, was reduced in both mutants at the same stage. Runx2 expression was unaffected in the coronal suture; in contrast, expression of the downstream ossification marker Spp1 was delayed. Double homozygous pups showed substantial reduction of alkaline phosphatase expression throughout the mineralized skull vault; they died at birth due to defects of the heart, lungs and diaphragm not previously associated with Alx4 or Msx2. Our observations suggest that Alx4 and Msx2 are partially functionally redundant, acting within a network of transcription factors and signalling events that regulate the rate of osteogenic proliferation and differentiation at a stage after the commitment of mesenchymal stem cells to osteogenesis.
Integrin expression in cells of the intervertebral disc
Authors: Nettles Dana L. , Richardson William J. , Setton Lori A. 
Published: May 2004

AbstractIn this study, we investigated the profile of integrin expression in human and porcine intervertebral disc tissue. Differences in extracellular matrix composition between anulus fibrosus (AF) and nucleus pulposus (NP) regions of the disc, as well as differences in cellular responses to environmental stimuli, suggest a role for integrins in presenting matrix signals that may mediate these responses. Human disc tissue and porcine AF and NP tissue were stained with antibodies to alpha integrin subunits 1–6, V and IIb, and beta integrin subunits 1–6 and graded for evidence of positive staining on a scale from 0 (no staining) to 3 (high incidence of staining). Human tissue expressed α and β integrin subunits shown to be present in articular cartilage, including α1, α5 and αV. Porcine AF tissue expressed similar integrin subunits to human disc, with both expressing α1, α5, β1, β3 and β5 subunits, whereas porcine NP tissue expressed higher levels of α6, β1 and β4 than AF tissue. The expressed subunits are known to interact with proteins including collagens, fibronectin and laminin; however, additional studies will be required to characterize the interactions of the integrin subunits with specific matrix constituents, as well as their specific involvement in regulating environmental stimuli.
The Desirable Organizational Structure for Evolutionary Firms in Static Landscapes
Authors: Garrido Nicolás 
Published: May 2004

ABSTRACTIn addition to the common analysis of the KauffmanNKmodel where the value ofKand the structure of interaction are given, the aim of this paper is to study what the values of these two parameters would be if they were endogenized. Thus, a model is proposed where firms and business schools coordinate to search for high peaks in their respective landscapes using evolutionary algorithms. The main result coming from the analysis of the model is that agents, using evolutionary algorithms, attempt to simplify the problems of coordination and this, over time, produces the existence in the economy of agents using many different strategies.
Contrasting movement patterns in two species of chequerspot butterflies,Euphydryas auriniaandMelitaea phoebe, in the same patch network
Authors: Wang Rongjiang , Wang Yifei , Chen Jiejun , Lei Guangchun , Xu Rumei 
Published: May 2004

Abstract. 1. Mark–release–recapture studies were conducted on two species of chequerspot butterfly,Euphydryas auriniaandMelitaea phoebe, in the same habitat patch network in Yanjiaping, a small basin in the Taihang Mountains, north‐west of Beijing, China, in 2000.2.Euphydryas auriniatended to stay in the habitat patches and to move to neighbouring patches, whereasM. phoebemoved widely among patches in the entire network.3. The parameters of the virtual migration model showed higher daily emigration propensity inM. phoebeand inE. auriniamales than inE. auriniafemales, and significantly greater average daily movement distance inM. phoebethan inE. aurinia.4. The results are consistent with the previous findings showing genetic structuring among local populations ofE. auriniabut not among local populations ofM. phoebe.5. Based on the genetic and ecological results, it was concluded thatE. auriniahas a classic metapopulation in the study area, whereasM. phoebeappears to have a source–sink metapopulation.6. In 2000, when there was an overall increase in the abundance of the two species, the limited mobility ofE. auriniaresulted in an increase in the average local population size, whereas the increase in the number of local populations inM. phoebewas due to its high mobility.
Optimal Dynamic Trading Strategies
Authors: Breeden Douglas T. 
Published: May 2004

This article presents a straightforward technique for computing solutions to discrete, multi‐period consumption/investment problems. It solves for the optimal stochastic consumption plans, as well as the optimal dynamic trading strategies that maximize utility for an individual. The technique permits general utility functions that may or may not be time‐separable. It also allows general changes in the investment opportunity set and allows the user to impose upper and lower bounds on trading behaviour. Divergent borrowing and lending rates can be handled, as can stochastic labour income risks. Computed solutions verify the predictions of well‐known intertemporal works by Merton, Breeden and others. J.E.L.:G13).