bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel mutation in the tyrosine kinase domain of FGFR2 in a patient with Pfeiffer syndrome
Authors: Zankl Andreas , Jaeger Gudrun , Bonafé Luisa , Boltshauser Eugen , Superti‐Furga Andrea 
Published: November 2004

AbstractMutations in the fibroblast growth factor receptor 2 (FGFR2) cause a variety of craniosynostosis syndromes. The mutational spectrum tends to be narrow with the majority of mutations occurring in either exon IIIa or IIIc or in the intronic sequence preceding exon IIIc. Mutations outside of this hotspot are uncommon and the few identified mutations have demonstrated wide clinical variability, making it difficult to establish a clear‐cut genotype–phenotype correlation. To better delineate the clinical picture associated with these unusual mutations, we describe a severely affected patient with Pfeiffer syndrome and a missense mutation in the tyrosine kinase (TK) domain of FGFR2. © 2004 Wiley‐Liss, Inc.
Somatic mosaicism of chromosome 7 in a highly proliferating melanocytic congenital naevus in a ring chromosome 7 patient
Authors: Mehraein Yasmin , Ehlhardt Sandra , Wagner Arnold , Göttert Elisabeth , Tilgen Wolfgang , Zang Klaus D. , Dill‐Müller Dorothee 
Published: November 2004

AbstractRing chromosome 7 is a rare but well documented chromosomal aberration in man. So far at least 14 cases have been reported in the literature showing a variable but distinct pattern of phenotypic characteristics in affected individuals. Besides others, skin findings as pigmented naevi are especially frequent. Loss of chromosomal material from the terminal chromosome arms in the structurally abnormal ring chromosome 7 as well as somatic mosaicism with loss or gain of chromosome 7 has been suggested to be responsible for the clinical symptoms. We now report another case of a ring chromosome 7 in a 14‐year‐old boy with multiple remarkable congenital naevi, where we could demonstrate for the first time somatic mosaicism showing significant gain of chromosome 7 within a highly proliferating melanocytic congenital naevus (MCN). © 2004 Wiley‐Liss, Inc.
Subcutaneous neurofibromas are associated with mortality in neurofibromatosis 1: A cohort study of 703 patients
Authors: Khosrotehrani Kiarash , Bastuji‐Garin Sylvie , Riccardi Vincent M. , Birch Patricia , Friedman Jan M. , Wolkenstein Pierre 
Published: November 2004

AbstractNeurofibromatosis 1 (NF1) is a common genetic disorder with an autosomal dominant mode of inheritance, an increased morbidity and mortality, and a shorter lifespan. Although the disease is fully penetrant by the age of 8, the variability in symptoms and complications is high, even among members of the same family. The aim of this study was to identify easily recognizable clinical features that may be associated with mortality in a cohort of patients affected with NF1. We used prospectively collected data from the Neurofibromatosis Institute Database (NFID) and included in our analysis 703 patients who fulfilled the NIH diagnostic criteria for NF1. Clinical, especially dermatological features were tested as potential factors associated with mortality. Among the patients, 405 (57.6%) were children and 298 (42.4%) were adults. The mean follow‐up was 2.4 years (median = 0.98, range: 0–15.3 years). Forty patients died during follow‐up, mostly due to tumor development such as sarcoma (n = 18). In the adult population, subcutaneous neurofibromas (odds ratio [OR] = 3.6, 95% confidence interval (CI): [1.2–11.3], P = 0.02) and male gender (OR = 5.6, [1.5–20.9], P = 0.004) were independent predictors of mortality after adjustment for age. Among children, the presence of facial plexiform neurofibromas and pruritus were significantly associated with mortality in univariate analysis. Our study describes independent risk factors of mortality in a large cohort of adult and pediatric patients. Close follow‐up should be obtained for patients presenting with subcutaneous neurofibromas. © 2004 Wiley‐Liss, Inc.
Autosomal dominant flat umbilicus
Authors: Leung Alexander K.C. , McLeod D. Ross 
Published: November 2004

AbstractWe describe a Chinese family among whom five members in three generations had a flat umbilicus with vertical and male to male transmission indicative of autosomal dominant inheritance. Except the proband, who also had Tetralogy of Fallot, other affected members had a flat umbilicus as an isolated anomaly. Autosomal dominant transmission of isolated flat umbilicus has not been reported previously. © 2004 Wiley‐Liss, Inc.
Antioxidant treatment improves in vivo cardiac and skeletal muscle bioenergetics in patients with Friedreich's ataxia
Authors: Lodi Raffaele , Hart Paul E. , Rajagopalan Bheeshma , Taylor Doris J. , Crilley Jenifer G. , Bradley Jane L. , Blamire Andrew M. , Manners David , Styles Peter , Schapira Anthony H.V. , Cooper J. Mark 
Published: November 2004

AbstractFriedreich's ataxia (FA) is the most common form of autosomal recessive spinocerebellar ataxia and is often associated with a cardiomyopathy. The disease is caused by an expanded intronic GAA repeat, which results in deficiency of a mitochondrial protein called frataxin. In the yeast YFH1 knockout model of the disease there is evidence that frataxin deficiency leads to a severe defect of mitochondrial respiration, intramitochondrial iron accumulation, and associated production of oxygen free radicals. Recently, the analysis of FA cardiac and skeletal muscle samples and in vivo phosphorus magnetic resonance spectroscopy (31P‐MRS) has confirmed the deficits of respiratory chain complexes in these tissues. The role of oxidative stress in FA is further supported by the accumulation of iron and decreased aconitase activities in cardiac muscle. We used 31P‐MRS to evaluate the effect of 6 months of antioxidant treatment (Coenzyme Q10 400 mg/day, vitamin E 2,100 IU/day) on cardiac and calf muscle energy metabolism in 10 FA patients. After only 3 months of treatment, the cardiac phosphocreatine to ATP ratio showed a mean relative increase to 178% (p = 0.03) and the maximum rate of skeletal muscle mitochondrial ATP production increased to 139% (p = 0.01) of their respective baseline values in the FA patients. These improvements, greater in prehypertrophic hearts and in the muscle of patients with longer GAA repeats, were sustained after 6 months of therapy. The neurological and echocardiographic evaluations did not show any consistent benefits of the therapy after 6 months. This study demonstrates partial reversal of a surrogate biochemical marker in FA with antioxidant therapy and supports the evaluation of such therapy as a disease‐modifying strategy in this neurodegenerative disorder.
Superoxide stress identifies neurons at risk in a model of ataxia‐telangiectasia
Authors: Quick Kevin L. , Dugan Laura L. 
Published: November 2004

AbstractAtaxia‐telangiectasia (A‐T) is an autosomal recessive disorder caused by mutations in the ATM gene. A‐T children demonstrate sensitivity to ionizing radiation, predisposition to hematological malignancies, and telangiectasias. However, the hallmark of A‐T is fulminant degeneration of cerebellar Purkinje cells accompanied by a progressive ataxia with features of both cerebellar and basal ganglia dysfunction. Although the ATM gene product (ATM) is known to be involved in DNA repair, the mechanisms that link loss of ATM with neurodegeneration remain unknown. Recently, it has been suggested that abnormalities in redox status contribute to the A‐T phenotype. To address this question in the nervous system, we measured reactive oxygen species (ROS) in brain regions and specific neuronal populations in ATM−/− mice. We found increased ROS levels in cerebellum and striatum but not cortex of ATM−/− mice compared to ATM+/+ mice. Confocal microscopic examination revealed elevated superoxide levels in cerebellar Purkinje cells and nigral dopaminergic neurons but not cortical neurons, thus mapping increased superoxide levels onto the neuronal populations selectively affected in A‐T. These data are the first demonstration of elevated levels of ROS in neurons at risk in any genetic neurodegenerative disorder and, furthermore, suggest that ATM acts as a pro‐survival signal in post‐mitotic Purkinje cells and dopaminergic neurons by modifying superoxide radical handling in these selectively vulnerable neurons.
How long do new‐onset seizures in children last?
Authors: Shinnar Shlomo , Berg Anne T. , Moshe Solomon L. , Shinnar Reuel 
Published: November 2004

AbstractAlthough there are data on the duration of seizures in patients with refractory epilepsy, little is known about the duration of seizures in nonrefractory epilepsy populations. In a prospective study, seizure duration was determined in 407 children with a first unprovoked seizure using a structured interview and review of medical and ambulance records. Analysis focused on the distribution of seizure duration and on the conditional probability that a seizure would stop once it had already lasted for a specified time. Seizures lasted ≥5 minutes in 50% of cases, ≥10 minutes in 29%, ≥20 minutes in 16%, and ≥30 minutes in 12%. Seizure duration data were best fit as the sum of two exponential distributions, one with a mean of 3.6 minutes accounting for 76% of cases and the other with a mean of 31 minutes accounting for 24% of cases. The longer a seizure lasted, the less likely it was to stop within the next few minutes. In the 182 children with 2 or more seizures, the durations of the first and second seizures were highly correlated (r = 0.395, p < 0.0001). We conclude that the distribution of seizure duration in children with a first unprovoked seizure differs markedly from that observed in patients with refractory epilepsy. A subgroup of patients are predisposed to prolonged seizures. The data suggest that, once a seizure lasts for more than 5–10 minutes, it is unlikely to stop spontaneously within the next few minutes, and intervention is therefore indicated. These findings also support the continued use of the current definition of status epilepticus as a seizure lasting for 30 minutes or longer for epidemiologic studies.
Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation
Authors: Nelson Karin B. , Grether Judith K. , Croen Lisa A. , Dambrosia James M. , Dickens Benjamin F. , Jelliffe Laura L. , Hansen Robin L. , Phillips Terry M. 
Published: November 2004

AbstractThere has been little exploration of major biologic regulators of cerebral development in autism. In archived neonatal blood of children with autistic spectrum disorders (n = 69), mental retardation without autism (n = 60), or cerebral palsy (CP, n = 63) and of control children (n = 54), we used recycling immunoaffinity chromatography to measure the neuropeptides substance P (SP), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase–activating polypeptide (PACAP), calcitonin gene–related peptide (CGRP), and the neurotrophins nerve growth factor (NGF), brain‐derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4/5 (NT4/5). Neonatal concentrations of VIP, CGRP, BDNF, and NT4/5 were higher (ANOVA, all p values < 0.0001 by Scheffe test for pairwise differences) in children in the autistic spectrum and in those with mental retardation without autism than in control children. In 99% of children with autism and 97% with mental retardation, levels of at least one of these substances exceeded those of all control children. Concentrations were similar in subgroups of the autistic spectrum (core syndrome with or without mental retardation, other autistic spectrum disorders with or without mental retardation) and in the presence or absence of a history of regression. Among children with mental retardation, concentrations did not differ by severity or known cause (n = 11, including 4 with Down syndrome). Concentrations of measured substances were similar in children with CP as compared with control subjects. SP, PACAP, NGF, and NT3 were not different by diagnostic group. No measured analyte distinguished children with autism from children with mental retardation alone. In autism and in a heterogeneous group of disorders of cognitive function, overexpression of certain neuropeptides and neurotrophins was observed in peripheral blood drawn in the first days of life.
Placebo‐controlled clinical trials in multiple sclerosis: Ethical considerations
Authors: Lublin Fred D. , Reingold Stephen C. ,   National Multiple Sclerosis Society (USA) Task Force on Placebo‐Controlled Clinical Trials in MS
Published: November 2004

AbstractThe availability of partially effective therapies for some forms of multiple sclerosis (MS) raises practical and ethical issues for future placebo‐controlled clinical trials. An international Task Force of clinicians, statisticians, ethicists and regulators was convened to discuss these issues and develop consensus. The Task Force concluded that placebo‐controlled clinical trials in forms of MS for which partially effective therapies exist were ethical, so long as study subjects were fully apprised of the availability of such therapies and were encouraged to pursue them outside of a clinical trial. Patients who decline to utilize available treatments, after proper education and counseling, or those that fail all therapies can be considered to have no treatment alternatives and thus may participate in a placebo‐controlled trial.
3‐hydroxy‐3‐methylglutaryl‐CoA lyase deficiency in an adult with leukoencephalopathy
Authors: Bischof Felix , Nägele Thomas , Wanders Ronald J. A. , Trefz Friedrich K. , Melms Arthur 
Published: November 2004

Abstract3‐Hydroxy‐3‐methylglutaryl‐CoA lyase deficiency is a disorder of leucine metabolism that usually presents with recurrent episodes of life‐threatening hypoglycemia during early childhood. We report on a 36‐year‐old woman with seizures, recurrent metabolic disturbances, and severe leukoencephalopathy. The diagnosis was made by analysis of amino acids in urine and serum and was confirmed by demonstration of the deficient enzyme in cultured skin fibroblasts. The patient improved clinically on oral L‐carnitine substitution. This treatable condition can remain unrecognized in adults and should be considered a potential cause of leukoencephalopathy. Ann Neurol 2004;56:727–730
Investigation into etching mechanism of polyethylene terephthalate (PET) films treated in helium and oxygenated‐helium atmospheric plasmas
Authors: Matthews Suzanne R. , Hwang Yoon J. , McCord Marian G. , Bourham Mohamed A. 
Published: November 2004

AbstractThis research makes an investigation into the etching mechanism of atmospheric plasma conditions on the surface of polyethylene terephthalate (PET) films. Two types of untreated PET films (S/200 and S/500) were exposed to plasma for 0 to 5.0 min in 30‐s increments. The first set of each film type was treated in helium plasma, while the second was treated in oxygenated‐helium plasma. Differential Scanning Calorimetry (DSC) was used to characterize pre‐ and post‐exposure films. Weight changes and the degree of solubility were also determined. Based on peak area results, the percent crystallinity of PET S/200 increased by an average of 4.57% (helium treated) and 13.56% (oxygenated‐helium treated), while the S/500 showed only a small increase. There was no significant change in the melting or crystallization temperatures of either film type, indicating a decrease in amorphous content versus an increase in crystalline material. Weight loss analysis supports this theory. Solubility testing revealed a continual decrease in swelling as exposure time was increased. A model was developed to predict the change in the degree of solubility for polyphase surfaces considering the etching rate per phase. The model was applied to PET with good correlation between the model and experimental data. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2383–2389, 2004
Copolymeric photoinitiators containing in‐chain thioxanthone and coinitiator amine for photopolymerization
Authors: Jiang Xuesong , Yin Jie 
Published: November 2004

AbstractTwo kinds of copolymeric macromolecular photoinitiator, PTXPM and PTXPC, were prepared by introducing methylacryloyl or cinnamoyl groups to the side chain of PTXP. The photopolymerizations of poly(propylene glycol)diacrylate (PPGDA) and trimethylolpropane triacrylate (TMPTA), using PTXPM and PTXPC as photoinitiators, were studied by photo‐DSC. PTXPM and PTXPC have UV–vis spectra similar to that of PTXP with blue‐shift absorption maxima. The photopolymerization behavior of TMPTA, initiated by three photoinitiators, appears similar to that of PPGDA. Compared with PTXP and PTXPC, PTXPM gives higher polymerization rate and final conversion, in photopolymerization of PPGDA and TMPTA, which shows that the introduction of methyl acrylate to the PTXP chain has a greater effect on photopolymerization of PPGDA and TMPTA than that of cinnamoyl acrylate. The polymerization rate and final conversion, for photopolymerization of PPDGA initiated by PTXP, can be more effectively increased by the introduction of methyl acrylate group to the PTXP chain, than are those for TMPTA. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2395–2400, 2004
Electron‐beam curing of bismaleimide‐reactive diluent resins
Authors: Li Yuntao , Morgan Roger J. , Tschen Francisco , Sue H.‐J. , Lopata Vince 
Published: November 2004

AbstractElectron‐beam (E‐beam) curing of 4,4′‐bismaleimidodiphenylmethane (BMPM)/BMI‐1,3‐tolyl/o,o′‐diallylbisphenol A (DABPA)–based bismaleimide (BMI) systems and their mixing with various reactive diluents, such as N‐vinylpyrrolidone (NVP) and styrene, were investigated to elucidate how temperature, electron‐beam dosage, and diluent concentration affect the cure extent. The effect of free‐radical initiator on the cure reactions was also studied. It was found that low‐intensity E‐beam exposures cannot cause the polymerization of BMI. High‐intensity E‐beam exposures give high reaction conversion attributed to a high temperature increase, which induced thermal curing. It was shown that the dilution and activation of NVP in BMI cause a more complete BMI cure reaction under E‐beam radiation. BMI/NVP can be initiated easily by low‐intensity E‐beam without thermal curing. FTIR studies indicate that about 70% of the reaction is complete for BMI/NVP with 200 kGy dosage exposure at 10 kGy per pass. The sample temperature only reaches about 75°C. The free‐radical initiator, dicumyl peroxide, can accelerate the reaction rate at the beginning of E‐beam exposure, but does not affect the final reaction conversion. The increase of the concentration of NVP in the BMI/NVP systems increases the reactive conversions almost linearly. © 2004 Wiley Periodicals Inc. J Appl Polym Sci 94: 2407‐2416, 2004
Synthesis and biological evaluation of novel 2′, 3′, 4′‐triply branched carbocyclic nucleosides as potential antiviral agents
Authors: Ko Ok Hyun , Hong Joon Hee 
Published: November 2004

AbstractNovel 2′, 3′, 4′‐triply branched carbocyclic nucleosides were synthesized in this study. The introduction of two methyl groups in the 2′‐ and 3′‐position was accomplished by a Horner‐Wadsworth‐Emmons reaction and isopropenyl magnesium bromide addition, respectively. The construction of the required 4′‐quaternary carbon was carried out using a [3, 3]‐sigmatropic rearrangement. Bis‐vinyls were successfully cyclized using a Grubbs' catalyst II. The natural bases (adenine, cytosine) were efficiently coupled using a Pd(0) catalyst. The antiviral activities of the synthesized compounds were evaluated against HIV‐1, HSV‐1, HSV‐2 and HCMV. Compound 30 displayed moderate anti‐HCMV activity (EC50 = 30.1 μg/mL), without exhibiting any cytotoxicity at up to 100 μM.
Archaeological prospection of the Dutch perimarine landscape by means of magnetic methods
Authors: Kattenberg A. E. , Aalbersberg G. 
Published: November 2004

AbstractFluxgate gradiometer surveys on two sites in the coastal plains of The Netherlands showed unexpected results. On the one hand, archaeological features, identified by coring or test trenching, were undetectable owing to a lack of sufficient magnetic contrast between the infill of the archaeological structures and the surrounding natural (salt marsh) sediments. This lack of contrast was shown to be caused by the iron mineralogy and not by iron deficiency of the soil. On the other hand, geological features, interpreted as anoxic shallow creek fills, showed with surprising clarity. Analysis of black‐stained deposits underlying the features identified pyrite and associated iron sulphide minerals as the cause for the magnetic anomalies. The complex iron sulphide/oxide mineralogy of salt marsh environments, coupled with geological history of the sites with multiple marine inundations, indicate that detection and interpretation of magnetic anomalies in the coastal zone of The Netherlands requires both thorough knowledge of the geology and further research into the geochemistry of these deposits. Copyright © 2004 John Wiley & Sons, Ltd.
Lectin‐like oxidized low‐density lipoprotein receptor 1 mediates matrix metalloproteinase 3 synthesis enhanced by oxidized low‐density lipoprotein in rheumatoid arthritis cartilage
Authors: Kakinuma Takumi , Yasuda Tadashi , Nakagawa Takefumi , Hiramitsu Teruko , Akiyoshi Miki , Akagi Masao , Sawamura Tatsuya , Nakamura Takashi 
Published: November 2004

AbstractObjectiveTo investigate for the presence of oxidized low‐density lipoprotein (ox‐LDL) and lectin‐like oxidized LDL receptor 1 (LOX‐1) in cartilage specimens from rheumatoid arthritis (RA) joints and to determine whether the interaction of ox‐LDL with LOX‐1 can induce matrix metalloproteinase 3 (MMP‐3) in articular cartilage explant culture.MethodsHuman articular cartilage specimens obtained from patients with RA, osteoarthritis (OA), and femoral neck fractures were examined for LOX‐1 and ox‐LDL by confocal fluorescence microscopy. The association between ox‐LDL and LOX‐1 was evaluated by immunofluorescence analysis. Articular cartilage specimens from patients with femoral neck fractures were incubated with ox‐LDL, with or without preincubation with neutralizing anti–LOX‐1 antibody. MMP‐3 synthesis by chondrocytes in explant cartilage was evaluated by immunofluorescence, and protein secretion into conditioned medium was monitored by immunoblotting and enzyme‐linked immunosorbent assay.ResultsThe majority of the RA chondrocytes stained positively with both anti–LOX‐1 and anti–ox‐LDL antibodies; however, no positive cells were found in OA and normal cartilage specimens. Anti–LOX‐1 antibody suppressed the binding of DiI‐labeled ox‐LDL to chondrocytes in explant culture, suggesting that the interaction was mediated by LOX‐1. In contrast to native LDL, ox‐LDL induced MMP‐3 synthesis by articular chondrocytes in association with the induction of LOX‐1, which resulted in enhanced secretion of MMP‐3 into the culture medium. Anti–LOX‐1 antibody reversed ox‐LDL–stimulated MMP‐3 synthesis to control levels.ConclusionOx‐LDL, principally mediated by LOX‐1, enhanced MMP‐3 production in articular chondrocytes. Increased accumulation of ox‐LDL with elevated expression of LOX‐1 in RA cartilage indicates a specific role of the receptor–ligand interaction in cartilage pathology in RA.