bluuebunny/crossref_metadata_2025_split huggingface dataset:
An investigation of the disclosure process and support needs of BRCA1 and BRCA2 carriers
Authors: Segal Jordana , Esplen Mary Jane , Toner Brenda , Baedorf Sylvia , Narod Steven , Butler Kate 
Published: February 2004

AbstractDisclosure of the results of a positive genetic mutation to offspring can be challenging. The purpose of this study was to investigate the content and process of disclosure from BRCA1/2 carriers to their offspring. A semi‐structured questionnaire focused on the disclosure processes between parent and offspring. Thirty‐one/40 mothers with BRCA1/2 mutations completed the cross‐sectional survey. Sixteen carriers (51.6%) chose to disclose their results to all of their children, thirteen carriers (41.9%) chose not to disclose their results, and two carriers (6.5%) chose to disclose to some of their children. The age of a child appeared to be the most significant contributing factor in the decision to disclose. The mean age of the offspring who learned of the positive test result was 24.3 years with most carriers advocating the ideal age range for disclosure from 19 to 25 years. There was a discrepancy between actual and potential disclosure topics between those who had disclosed and those who had not disclosed at the time of the survey. Women who disclosed their result tended to do so alone, within a week of learning their own results, equally to male and female offspring and expressed that the relationships between themselves and their children had strengthened since revealing the presence of a genetic mutation in the family. Women who had not disclosed the results of their genetic test to offspring were significantly more interested in receiving additional individual counseling, educational videos, and email newsletters that focus on disclosure of this complex and life altering information compared to those who had already disclosed. Disclosure of BRCA1/2 results is determined primarily by age of offspring, is usually done by women alone, relatively soon after receiving results and appears to enhance the relationships between mothers and offspring. Both disclosed and non‐disclosed carriers demonstrated significant interest in a variety of interventions to support the disclosure process. © 2003 Wiley‐Liss, Inc.
Clinical and radiographic findings in multiple epiphyseal dysplasia caused by MATN3 mutations: Description of 12 patients
Authors: Mäkitie Outi , Mortier Geert R. , Czarny‐Ratajczak Malwina , Wright Michael J. , Suri Mohnish , Rogala Piotr , Freund Margarida , Jackson Gail C. , Jakkula Eveliina , Ala‐Kokko Leena , Briggs Michael D. , Cole William G. 
Published: February 2004

AbstractMultiple epiphyseal dysplasia (MED) is characterized by pain and stiffness in joints and delayed and irregular ossification of epiphyses. Causative mutations have been recognized in six different genes. We have identified disease‐causing mutations in the gene encoding matrilin‐3, an extracellular matrix protein, in seven families with autosomal dominant MED. Review of the clinical and radiographic features in 12 of the affected family members shows a uniform pattern of skeletal anomalies in all patients with considerable degree of variability in severity, both between and within families. The characteristic clinical findings are onset of symptoms in early childhood with predominance of knee and hip related complaints, normal stature, and early‐onset osteoarthritis. Radiographs show small and irregular epiphyses and mild metaphyseal irregularities and striations, especially at the knees and hips and mild spinal changes. Despite overlap, both clinically and radiographically, with other forms of MED, the described features may help to differentiate this particular form from other entities within the MED spectrum. © 2003 Wiley‐Liss, Inc.
Novel mutation in the SLC19A2 gene in an African‐American female with thiamine‐responsive megaloblastic anemia syndrome
Authors: Lagarde William H. , Underwood Louis E. , Moats‐Staats Billie M. , Calikoglu Ali S. 
Published: February 2004

AbstractThiamine‐responsive megaloblastic anemia (TRMA) syndrome is an autosomal recessive disorder characterized by diabetes mellitus (DM), progressive sensorineural deafness, and thiamine‐responsive anemia. Mutations in the SLC19A2 gene encoding a high‐affinity thiamine transporter protein THTR‐1 are responsible for the clinical features associated with TRMA syndrome. We report an African‐American female with TRMA‐syndrome associated with thyroid disease and retinitis pigmentosa caused by a novel mutation in the SLC19A2 gene. The patient presented at 12 months of age with paroxysmal atrial tachycardia and hepatosplenomegaly. One month later, she developed DM requiring intermittent insulin therapy. At 2‐1/2 years of age, profound sensorineural hearing loss was discovered. By 4 years of age, daily insulin therapy (0.5 U/kg/day) was instituted and her insulin requirement gradually increased to 1.0 U/kg/day by 9 years of age. She developed optic atrophy, retinitis pigmentosa, and visual impairment by 12 years of age with severe restriction of peripheral vision by 16 years. At age 19, a thiamine‐responsive normocytic anemia was discovered. She was diagnosed with autoimmune thyroiditis at 20 years and she experienced a psychotic episode associated with a mood disorder at age 21. With oral thiamine therapy, her insulin requirement decreased by 30% over a 20 month period. Molecular analysis revealed that the patient is homozygous for a missense mutation (C152T) in exon 1 of the SLC19A2 gene. © 2003 Wiley‐Liss, Inc.
Congenital malformations in births with orofacial clefts among 3.6 million California births, 1983–1997
Authors: Shaw Gary M. , Carmichael Suzan L. , Yang Wei , Harris John A. , Lammer Edward J. 
Published: February 2004

AbstractFew population‐based epidemiologic data are available on malformation phenotypes that co‐occur with orofacial clefts. We explored the occurrence of structural congenital malformations in offspring with cleft palate (CP) and in offspring with cleft lip with or without CP (CLP), using data from a population‐based active surveillance system. Ascertainment was performed among 3,548,991 liveborn and 23,239 stillborn offspring of California women who delivered in nonmilitary hospitals during the period, 1983–1997. Structural congenital malformations were found in 91,888 births. Among them, 2,343 had CP and 4,072 had CLP. Malformations were grouped according to 3‐ and 4‐digit codes of the British Pediatric Association (BPA). Prevalences of each malformation grouping, defined by these codes, were calculated among: (1) all births with CP; (2) all births with CLP; (3) all births without CP or CLP but with another structural malformation; and (4) all births in the population at risk. These various prevalence measures were the basis of estimating relative risks. Observed relative risks indicated that some phenotypes were more likely and some were less likely to co‐occur with either CP or CLP, with relative risks ranging from 0.5 to 2.4. For both CP and CLP, estimated relative risks were highest for malformations involving the respiratory system and lowest for spina bifida. The exclusion of all births (n = 10,702) with chromosomal anomalies from comparisons did not materially alter observed relative risk estimates. Computations extended to 4‐digit level BPA codes revealed elevated risks for a number of more specific diagnoses seen within the larger (3‐digit level) groupings defined as eye, ear, respiratory, upper alimentary tract, and other musculoskeletal anomalies. In this large population‐based cohort of infants and fetuses with CLP or CP, we observed several noncleft malformation groupings to be more common and others to be less common in their co‐occurrence with orofacial clefts relative to their co‐occurrence with any other malformation. These observed patterns tended to be similar for CP and for CLP. © 2003 Wiley‐Liss, Inc.
Novel mutation, L371V, causing multigenerational Gaucher disease in a Lebanese family
Authors: Shamseddine A. , Taher A. , Fakhani S. , Zhang M. , Scott C. Ronald , Habbal M.Z. 
Published: February 2004

AbstractWe have identified six individuals over three generations within a Lebanese–Arab family affected with Gaucher disease. This family is unusual and informative because affected members are homozygous for a previously unidentified mutation, L371V. Clinical symptoms begin in early childhood and progress to moderately severe involvement by young adulthood. There is significant anemia, thrombocytopenia, and bony involvement, but no mental deterioration. The phenotype is more severe than the phenotype observed in the common mutation associated with type 1 Gaucher disease, N370S. It is unknown whether L371V is a private mutation limited to this family, or will prove to be a common mutation within the Lebanese population. © 2003 Wiley‐Liss, Inc.
Eye abnormalities in Fryns syndrome
Authors: Pierson Diane M. , Taboada Eugenio , Butler Merlin G. 
Published: February 2004

AbstractFryns syndrome is a rare, generally lethal, autosomal recessive multiple congenital anomaly (MCA) syndrome first described in 1979. Patients with the syndrome present with the classical findings of cloudy cornea, brain malformations, diaphragmatic defects, and distal limb deformities. Over 70 patients have been reported revealing a wide variety of phenotypic features. Although initially considered a major feature of Fryns syndrome, cloudy cornea has been relegated as a minor diagnostic sign and not commonly reported in patients since the original description. However, eye findings per se are not uncommon. Abnormal eye findings occasionally reported in Fryns syndrome potentially result in amblyopia and blindness, profoundly affecting neurologic outcome of those who survive the neonatal period. We reviewed 77 reported patients with Fryns syndrome and summarized the abnormal eye findings identified in 12 of the reported cases. In addition, we contribute three new patients with Fryns syndrome, one of which demonstrated unilateral microphthalmia and cloudy cornea. © 2003 Wiley‐Liss, Inc.
Cognition and anatomy in three variants of primary progressive aphasia
Authors: Gorno‐Tempini Maria Luisa , Dronkers Nina F. , Rankin Katherine P. , Ogar Jennifer M. , Phengrasamy La , Rosen Howard J. , Johnson Julene K. , Weiner Michael W. , Miller Bruce L. 
Published: February 2004

AbstractWe performed a comprehensive cognitive, neuroimaging, and genetic study of 31 patients with primary progressive aphasia (PPA), a decline in language functions that remains isolated for at least 2 years. Detailed speech and language evaluation was used to identify three different clinical variants: nonfluent progressive aphasia (NFPA; n = 11), semantic dementia (SD; n = 10), and a third variant termed logopenic progressive aphasia (LPA; n = 10). Voxel‐based morphometry (VBM) on MRIs showed that, when all 31 PPA patients were analyzed together, the left perisylvian region and the anterior temporal lobes were atrophied. However, when each clinical variant was considered separately, distinctive patterns emerged: (1) NFPA, characterized by apraxia of speech and deficits in processing complex syntax, was associated with left inferior frontal and insular atrophy; (2) SD, characterized by fluent speech and semantic memory deficits, was associated with anterior temporal damage; and (3) LPA, characterized by slow speech and impaired syntactic comprehension and naming, showed atrophy in the left posterior temporal cortex and inferior parietal lobule. Apolipoprotein E ε4 haplotype frequency was 20% in NFPA, 0% in SD, and 67% in LPA. Cognitive, genetic, and anatomical features indicate that different PPA clinical variants may correspond to different underlying pathological processes.
Tau haplotypes regulate transcription and are associated with Parkinson's disease
Authors: Kwok John B. J. , Teber Erdahl T. , Loy Clement , Hallupp Marianne , Nicholson Garth , Mellick George D. , Buchanan Daniel D. , Silburn Peter A. , Schofield Peter R. 
Published: February 2004

AbstractA primary haplotype (H1) of the microtubule‐associated protein Tau (MAPT) gene is associated with Parkinson's disease (PD). However, the mechanism for disease susceptibility remains unknown. We examined the promoter region of MAPT and identified single nucleotide polymorphisms and insertions of 1 to 11 nucleotides. These polymorphisms corresponded to the previously characterized haplotypes, H1 and H2, as well as a novel variant of the H1 haplotype, H1′. As observed in other studies, we demonstrated a significant association with the H1/H1 promoter genotype and PD in a cohort of 206 idiopathic late‐onset cases. This is in contrast with a panel of 13 early‐onset PD patients, for whom we did not detect any mutations in MAPT. By examining single nucleotide polymorphisms in adjacent genes, we showed that linkage disequilibrium does not extend beyond the MAPT haplotype to neighboring genes. To define the mechanism of disease susceptibility, we examined the transcriptional activity of the promoter haplotypes using a luciferase reporter assay. We demonstrated in two human cell lines, SK‐N‐MC and 293, that the H1 haplotype was more efficient at driving gene expression than the H2 haplotype. Our data suggest that an increase in expression of the MAPT gene is a susceptibility factor in idiopathic PD.
Gene therapy in a murine model for clinical application to multiple sclerosis
Authors: Weiner Leslie P. , Louie Katherine A. , Atalla Lilly R. , Kochounian Harold H. , Du Jing , Wei Wenqiang , Hinton David R. , Gordon Erlinda M. , Anderson W. French , McMillan Minnie 
Published: February 2004

AbstractFemale SJL/J mice, suffering from experimental autoimmune encephalomyelitis (EAE), were injected with 1 × 107 cells from a syngeneic fibroblast line transduced with a retroviral vector designed to encode proteolipid protein (101‐157) targeted for secretion. A striking abrogation of both clinical and histological signs of disease resulted. The treatment was efficacious when given after the first or the third relapses, protected naive mice from challenge with spinal cord homogenate, and was dose dependent. This strategy was devised to provide a systemic, antigen‐specific signal to pathogenic T cells in the absence of costimulation and, hence, render them anergic. Cytokine analyses of brain and spinal cord lymphocytes demonstrate that the treatment induces an antiinflammatory Th2 profile, indicating that this antigen‐specific therapy acts by a cytokine‐induced pathway. This study was designed for translation to the clinic. We envision using allogeneic transduced fibroblasts, encapsulated in a chamber, to deliver the antigen‐specific signal. This will enable us to use one therapeutic cell line for all patients and to remove the device should the therapy exacerbate disease.
Readthrough of dystrophin stop codon mutations induced by aminoglycosides
Authors: Howard Michael T. , Anderson Christine B. , Fass Uwe , Khatri Shikha , Gesteland Raymond F. , Atkins John F. , Flanigan Kevin M. 
Published: February 2004

AbstractWe report the translational readthrough levels induced by the aminoglycosides gentamicin, amikacin, tobramycin, and paromomycin for eight premature stop codon mutations identified in Duchenne's and Becker's muscular dystrophy patients. In a transient transfection reporter assay, aminoglycoside treatment results show that one stop codon mutation is suppressed significantly better (up to 10% stop codon readthrough) than the others; five show lower but statistically significant suppression (<2% stop codon readthrough); and two appear refractory to aminoglycoside treatment. Readthrough levels do not substantially vary between different sources of gentamicin, and, for this set of mutations, the efficiency of termination at the premature stop codon mutation does not appear to correlate with disease severity.
Reduced striatal [123I]FP‐CIT binding in SCA2 patients without parkinsonism
Authors: Varrone Andrea , Salvatore Elena , De Michele Giuseppe , Barone Paolo , Sansone Valeria , Pellecchia Maria Teresa , Castaldo Imma , Coppola Giovanni , Brunetti Arturo , Salvatore Marco , Pappatà Sabina , Filla Alessandro 
Published: February 2004

AbstractDegeneration of substantia nigra has been described in spinocerebellar ataxia type 2 (SCA2). In this study, dopamine transporter (DAT) density with [123I]FP‐CIT SPECT was studied in six SCA2 patients with no parkinsonian signs, six Parkinson's disease (PD) patients, and six controls. Marked striatal DAT loss was found in both SCA2 and PD patients. However, a more severe reduction in the caudate and a higher putamen to caudate ratio distinguished SCA2 from PD patients, suggesting a more uniform nigrostriatal impairment in SCA2. Striatal DAT density of SCA2 patients correlated with the severity of cerebellar ataxia.
Levodopa‐responsive aromatic L–amino acid decarboxylase deficiency
Authors: Chang Yuh Terng , Sharma Radhakant , Marsh J. Lawrence , McPherson John D. , Bedell Joey A. , Knust Andreas , Bräutigam Christa , Hoffmann Georg F. , Hyland Keith 
Published: February 2004

AbstractWe report three siblings, who were treated empirically with levodopa combined with carbidopa. There was an immediate therapeutic response. Biochemical investigation surprisingly showed the clinical phenotype to be caused by aromatic L–amino acid decarboxylase deficiency. Molecular characterization showed a homozygous point mutation (c.387 G→A) in exon 3. Kinetic studies showed the mutation to decrease the binding affinity for the substrate. This, combined with structural modeling suggesting alteration of active site configuration, provided an explanation for the therapeutic response to levodopa. Ann Neurol 2004
Synthesis and Properties of Allenic Natural Products and Pharmaceuticals
Authors: Hoffmann‐Röder Anja , Krause Norbert 
Published: February 2004

AbstractNowadays, about 150 natural products comprising an allenic or cumulenic structure are known. The chemistry of these compounds has turned out to be a very attractive and prolific area of interest: advances in the isolation and characterization of new allenic natural products have led to the establishment of efficient synthetic procedures which in many cases also open up an access to enantiomerically pure target molecules. Inspired by the intriguing biological activities of many allenic natural products, allene moieties are now systematically introduced in pharmacologically active classes of compounds (steroids, prostaglandins, amino acids, nucleosides). The functionalized allenes thus obtained often exhibit impressive activities as mechanism‐based enzyme inhibitors, cytotoxic, or antiviral agents. A prerequisite for further developments in this field is the efficient stereoselective synthesis of allene derivatives.
Polymerization of phenylacetylene catalysed by RhTp(cod) and RhBp(cod) in ionic liquids: effect of alcohols and of tetraammonium halides
Authors: Trzeciak Anna M. , Ziółkowski Józef J. 
Published: February 2004

AbstractRhTp(cod) (1) and RhBp(cod) (2), almost inactive in CH2Cl2, became good catalysts of phenylacetylene polymerization in ionic liquids ([bmim]Cl, [bmim]BF4: bmim = 1‐butyl‐3‐methylimidazolium, [mokt]BF4: mokt = 1‐methyl‐3‐oktylimidazolium, [bumepy]BF4: 1‐butyl‐4‐methylpyridinium) and in CH2Cl2 in the presence of tetraammonium halides ([R4N]X, R = Bu, Et; X = Cl, Br). The highest yields of polyphenylacetylene with catalyst 1 were obtained in [bmim]Cl at 65°C (64% after 2 h) and in [mokt]BF4 at 20°C (56% after 24 h). In alcohols (CH3OH, (CH3)2CHOH, (CH3)3COH) as solvents, up to 100% of the polymer was produced. When a mixture of an ionic liquid and CH3OH was used as the reaction medium, the polymer yield was similar to the yield achieved in an ionic liquid only, but the molecular weight increased remarkably.Tetraammonium salts, [R4N]X, are co‐catalysts for 1, and the yield of the polymer increased in the order [Et4N]Br < [Bu4N]Br < [Et4N]Cl < [Bu4N]Cl. Polymers with molecular weights from 6900 to 38 800 Da were obtained with catalyst 2 in [R4N]Br or [R4N]Cl, whereas in ionic liquids ([bmim]Cl, [bmim]BF4) the corresponding molecular weights were higher, from 51 300 to 60 300 Da. Copyright © 2004 John Wiley & Sons, Ltd.
Specific binding of a biotinylated, metallocarbonyl‐labelled dendrimer to immobilized avidin detected by diffuse‐reflectance infrared Fourier transform spectroscopy
Authors: Rudolf Bogna , Zakrzewski Janusz , Celichowski Grzegorz , Salmain Michèle , Vessières Anne , Jaouen Gérard 
Published: February 2004

AbstractMolecular recognition between avidin covalently immobilized at the surface of acrylic resin beads and a transition metallocarbonyl tracer of the biotin ligand was detected using diffuse reflectance infrared Fourier transform spectroscopy. Copyright © 2004 John Wiley & Sons, Ltd.
Coordination complexes of 2‐thienyl‐ and 2‐furyl‐mercurials
Authors: Bell Norman A. , Crouch David J. , Jaffer Naznin E. 
Published: February 2004

AbstractThe reactions of di(2‐thienyl)mercury, 2‐thienylmercury chloride and 2‐furylmercury chloride with a variety of nitrogen‐ and phosphorus‐containing ligands have been studied. The presence of the electron‐withdrawing heteroatoms results in these mercurials being stronger acceptors than the corresponding phenylmercury compounds. The complexes have been characterized by elemental analysis, melting points, infrared, and 199Hg NMR spectroscopy. 2,9‐Dimethyl‐ and 3,4,7,8‐tetramethyl‐phenanthroline form 1:1 chelate complexes, as does 1,2‐bis(diphenylphosphino)ethane, whereas ethylenediamine and 2,2′‐bipyridyl do not form complexes. Though non‐chelating ligands such as 2,4′‐ and 4,4′‐bipyridyl do not form complexes, bis(diphenylphosphino)methane forms 1:2 complexes in which the ligand bridges two mercury atoms. Monodentate ligands, such as triphenylphosphine, cause disproportionation of the organomercury chloride. 2‐Thienylmercury chloride forms a 4:1 complex with 4,4′‐dipyridyl disulfide in which it is believed that a molecule of the organomercurial is coordinated to both of the nitrogen and both of the sulfur atoms. Copyright © 2004 John Wiley & Sons, Ltd.
The influence of bottom type and shelf position on biodiversity of tropical fish inside a recently enlarged marine reserve
Authors: Kendall Matthew S. , Christensen John D. , Caldow Christopher , Coyne Michael , Jeffrey Christopher , Monaco Mark E. , Morrison Wendy , Hillis‐Starr Zandy 
Published: February 2004

Abstract
A necessary component of implementing a successful marine reserve is the quantification of the biological resources that fall under its protection. Without such an initial assessment, the future effects of the reserve on the local habitat and biotic community cannot be quantified and will remain the subject of debate.
This study provides such a baseline assessment of fish diversity and habitat types within a recently enlarged marine reserve. Buck Island Reef National Monument, US Virgin Islands, was recently enlarged from approximately 4 km2 to over 76 km2. Areas of sand, seagrass, and hard‐bottom under protection were increased from 0.29 km2, 0.47 km2, and 1.96 km2 to 2.70 km2, 2.89 km2, and 18.30 km2 respectively when the Monument was expanded. A 53 km2 area of pelagic/deep‐water habitat with unknown bottom type is now also protected by the Monument.
Visual counts of fish within 25×4 m2 transects conducted during the day were used to assess fish community structure and habitat utilization patterns. Species richness, diversity, assemblage structure, and fish density were evaluated and compared among sand, seagrass, and hard‐bottom habitats. Hard‐bottom sites had over twice the mean species richness and diversity as sand and seagrass sites, and several times greater mean fish density.
Quantification of the fish community in pelagic and deep‐water habitats within the reserve is recommended to provide a more comprehensive assessment of the offshore areas of the reserve. Fish numbers, size, and diversity outside the reserve boundaries must also be evaluated to allow quantification of the effects of the marine reserve on the adjacent fish communities.
Copyright © 2004 John Wiley & Sons, Ltd.