bluuebunny/crossref_metadata_2025 huggingface dataset:
Agreement of job‐exposure matrix (JEM) assessed exposure and self‐reported exposure among adult leukemia patients and controls in Shanghai
Authors: Adegoke Olufemi J. , Blair Aaron , Ou Shu Xiao , Sanderson Maureen , Addy Cheryl L. , Dosemeci Mustafa , Zheng Wei
Published: February 2004

Background

Estimating a person's history of occupational exposure in case‐control studies is difficult.

Methods

Percent agreement between selected self‐reported occupational exposures and job‐exposure matrix (JEM) exposure assessment for all participants and various subgroups of a population‐based case‐control interview study of 486 leukemia subjects and 502 healthy controls in Shanghai was evaluated.

Results

With JEM as the “gold standard,” the sensitivities for self‐reported exposures ranged from 0.75 to 0.98. However, that for pesticide exposure was 0.44 in subjects >51 years old. Self‐reported exposures specificities ranged from 0.87 to 0.99. Agreement between self‐reported exposures and JEM assessment was good (kappa coefficients [κ]: 0.48–0.84). Variations in agreement for benzene exposure between males and females as well as between the direct interview and surrogate interview subgroups were observed.

Conclusions

The levels of agreement between self‐report and JEM in this study suggest that self‐reported exposures are a suitable method for assessing occupational exposures in this population. Am. J. Ind. Med. 45:281–288, 2004. © 2004 Wiley‐Liss, Inc.
Microcephaly, jejunal atresia, aberrant right bronchus, ocular anomalies, and XY sex reversal
Authors: Keegan Catherine E. , Vilain Eric , Mohammed Mansoor , Lehoczky Jessica , Dobyns William B. , Archer Steven M. , Innis Jeffrey W.
Published: February 2004

We present a patient with microcephaly, jejunal atresia, aberrant right tracheobronchial tree, mild left blepharoptosis, and corectopia (irregular pupil), left sectoral iris stromal hypoplasia and peripheral anterior synechia, and 46,XY sex reversal. Testosterone and dihydrotestosterone (DHT) levels were within normal limits for a male infant at 3 weeks of age. Gonadectomy at age 18 months revealed immature testis tissue and no evidence of Müllerian structures. PCR amplification of the androgen receptor (AR) gene and flanking genomic regions revealed no evidence for deletion. Array‐comparative genomic hybridization (array‐CGH) for assessment of gene dosage in other regions of the genome was normal. This patient represents a multiple anomaly disorder similar to intestinal atresia—ocular anomalies—microcephaly syndrome (MIM#243605) but incorporating 46,XY sex reversal with testicular tissue, demonstrating a defect in the sexual differentiation pathway. © 2003 Wiley‐Liss, Inc.
Neu–Laxova syndrome: Detailed prenatal diagnostic and post‐mortem findings and literature review
Authors: Manning Melanie A. , Cunniff Christopher M. , Colby Christopher E. , El‐Sayed Yasser Y. , Hoyme H. Eugene
Published: February 2004

Neu–Laxova syndrome (NLS) is a lethal, autosomal recessive multiple malformation syndrome with many features resulting from severe skin restriction and decreased fetal movement. It is characterized by ichthyosis, marked intrauterine growth restriction (IUGR), microcephaly, short neck, central nervous system (CNS) anomalies, limb deformities, hypoplastic lungs, edema, and abnormal facial features including severe proptosis with ectropion, hypertelorism, micrognathia, flattened nose, and malformed ears. We present two new patients with NLS with striking prenatal diagnostic findings and detailed post‐mortem examinations and review the previously described cases in the literature. Data from these patients suggest that the NLS represents a heterogeneous phenotype. Prenatal ultrasound findings of marked ocular proptosis in a growth restricted, edematous fetus should prompt consideration of a diagnosis of the NLS. © 2003 Wiley‐Liss, Inc.
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

Disclosure 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

Multiple 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

Thiamine‐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

Few 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

We 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

Fryns 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

We 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

A 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

Female 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

We 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

Degeneration 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

We 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
Titelbild: Fünfkernige Platin(II)‐Makrocyclen mit Nucleobasen (Angew. Chem. 10/2004)
Authors: Rauterkus Michael J. , Krebs Bernt
Published: February 2004

Metallocalixarene wie der im Titelbild gezeigte fünfkernige Platin(II)‐Makrocyclus wurden aus einem Cisplatin‐Analogon mit tertiären Aminliganden und der Nucleobase Uracil oder Thymin aufgebaut. Der für die Synthese dieser Makrocyclen eingesetzte Platin(II)‐Komplex zeigt aufgrund seiner Bindung an die DNA signifikante cytostatische Aktivität. Im Hintergrund ist ein Kristall von DNA aus Kalbsthymus dargestellt. Details zu diesem neuartigen Strukturtyp erfahren Sie in der Zuschrift von B. Krebs und M. J. Rauterkus auf S. 1321 ff.
Synthesis and Properties of Allenic Natural Products and Pharmaceuticals
Authors: Hoffmann‐Röder Anja , Krause Norbert
Published: February 2004

Nowadays, 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

RhTp(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

Molecular 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

The 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

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.
Conservation status of the San Christóbal pupfish Profundulus hildebrandi Miller (Teleostei: Profundulidae) in the face of urban growth in Chiapas, Mexico
Authors: Velázquez‐Velázquez Ernesto , Schmitter‐Soto Juan J.
Published: February 2004

1. Profundulus hildebrandi, the San Cristóbal pupfish, is a small cyprinodontiform fish endemic to the closed basin of San Cristóbal de Las Casas, a fast‐growing city in highland Chiapas, Mexico. This study constitutes the first population study of this endangered taxon.

2. In order to judge its conservation status, its distribution and habitat were described, and its population size was estimated through a capture–recapture technique. To the extent possible, present conditions of its habitat were compared with historic information, mainly old city maps and photographs.

3. Introduction of largemouth bass (Micropterus salmoides) coincided with local extirpation of P. hildebrandi. Other risk factors related to urban growth include pollution of streams, as well as habitat destruction, fragmentation, and modification; about 60% of the original pupfish habitat is heavily polluted by sewage.

4. Although its population size is apparently large (probably more than 8000), its very restricted distribution, its shrinking habitat and the increasing risk factors provide justification to consider P. hildebrandi as an endangered fish, according to the Mexican Official Norm and the Red Book of the IUCN. Copyright © 2004 John Wiley & Sons, Ltd.
Familial aggregation of genetically heterogeneous hypertrophic cardiomyopathy: A boy with LEOPARD syndrome due to PTPN11 mutation and his nonsyndromic father lacking PTPN11 mutations
Authors: Digilio M. Cristina , Pacileo Giuseppe , Sarkozy Anna , Limongelli Giuseppe , Conti Emanuela , Cerrato Fabiana , Marino Bruno , Pizzuti Antonio , Calabrò Raffaele , Dallapiccola Bruno
Published: February 2004

BACKGROUND

Nonsyndromic hypertrophic cardiomyopathy (HCM) is a primary cardiac disease transmitted as an autosomal dominant trait. Multiple chromosomal loci have been found to be involved in the etiology of this defect. LEOPARD syndrome is a genetic condition characteristically associated with HCM. Additional features of the syndrome include multiple lentigines, facial anomalies, sensorineural deafness, and growth retardation. Mutations in PTPN11, a gene encoding the protein tyrosine phosphatase SHP‐2 located at chromosome 12q24, have been identified in patients with LEOPARD syndrome.

CASES

We report here on a patient with HCM presenting with classic clinical features of LEOPARD syndrome, whose father also has HCM, but lacks phenotypic anomalies of the syndrome. Molecular analysis searching for PTPN11 mutations was performed in this family. A missense mutation (836A→G; Tyr279Cys) in exon 7 of PTPN11 gene was identified in the patient with LEOPARD syndrome, whereas no mutation in PTPN11 gene was detected in the father or in additional family members.

CONCLUSIONS

Aggregation of syndromic and nonsyndromic HCM in the same family is an unusual pattern of recurrence. Although genetic heterogeneity of LEOPARD and nonsyndromic HCM is not disputed, the existence of peculiar interactions linking genes causing nonsyndromic HCM and HCM in LEOPARD syndrome can be hypothesized. Different genes can work together, and a more severe cardiac phenotype can be due to additive effects. The involvement of familial susceptibility to specific cardiac malformations based on the presence of common predisposing factors can also be considered. Further molecular studies may shed light on these observations. Birth Defects Research (Part A), 2003. © 2004 Wiley‐Liss, Inc.
Secular decreasing trend of the frequency of hypospadias among newborn male infants in Spain
Authors: Martínez‐Frías María Luisa , Prieto David , Prieto Luis , Bermejo Eva , Rodríguez‐Pinilla Elvira , Cuevas Lourdes
Published: February 2004

BACKGROUND

The frequency of hypospadias is not uniform worldwide. Several countries have reported an increase in its frequency at birth. Although a better ascertainment of the minor forms has been considered as an explanation, the potential effect of environmental endocrine disrupters has also been proposed. We studied the secular trend of hypospadias in Spain over the past 22 years, separating the minor and major forms.

METHODS

We used data from the Spanish Collaborative Study of Congenital Malformations (ECEMC) registry, analyzing the frequency in two different periods: from 1978 to 1995, and from 1996 to 2002. To evaluate the “step” of the frequency between the two periods, we applied a parametric Student's t‐test, and the nonparametric Mann‐Whitney rank test.

RESULTS

The birth frequency of isolated and total hypospadias was quite stable between 1978 and 1995. In 1996, it decreased dramatically in a step, essentially due to isolated cases with minor forms of hypospadias. Study of the geographical distribution by the 17 Spanish regions showed that the frequency step occurred in nearly all of them.

CONCLUSIONS

It is difficult to consider that the observed decrease of the frequency of minor forms of hypospadias could be due to less accurate reporting of these minor forms in all 87 hospitals in the same year without any previous physician agreement. This decrease rather suggests a change in some product or exposure affecting the whole country. We think that the observed change in the frequency cannot be attributable to a lower exposure to endocrine disrupters or the voluntary interruption of gestation. Birth Defects Research (Part A) 67:000–000, 2003. © 2004 Wiley‐Liss, Inc.
Application of kinetic polymerase chain reaction and molecular beacon assays to pooled analyses and high‐throughput genotyping for candidate genes
Authors: Shi Min , Caprau Diana , Dagle John , Christiansen Lene , Christensen Kaare , Murray Jeffrey C.
Published: February 2004

BACKGROUND

The addition of DNA analysis to epidemiologic studies that have traditionally incorporated demographic and interview data can provide additional power and open new avenues for investigation. DNA can be obtained from a variety of tissues, but each has attendant variation in sample quantity, quality, and cost of acquisition. Analytic approaches for DNA genotyping are under constant development, but current applications allow small amounts (less than 2 ng per assay) of DNA to be used for genotyping.

METHODS

In this report, we designed effective assays for a spectrum of genes using either kinetic polymerase chain reaction (PCR) or molecular beacon applications. We also investigated the extent to which DNA use and reagent cost could be minimized. Kinetic PCR assays were also applied to investigate the potential of pooled sample analysis.

RESULTS

Our results show that small amounts of DNA can be successfully amplified in a high‐throughput fashion using both kinetic PCR and molecular beacon methods. Greater than 97% of the genotype results from these two methods are consistent. In addition, error rates in allele frequency measurements using DNA pools of 100 or more samples were often less than 1% and usually less than 3%, which provides another option for substantially minimizing the costs of genotyping in studies involving large numbers of individuals.

CONCLUSIONS

Effective assays have been designed for a spectrum of genes widely studied in birth defects, including: MTHFR, NAT1, TGFA, RFC1, PAX9, EPHX1, and SKI. An efficient assay has been designed for the detection of the presence of X and Y chromosomes, which can be applied to the studies of sex chromosome abnormalities or sample quality control. Birth Defects Research (Part A), 2004. © 2004 Wiley‐Liss, Inc.
Chemically induced supernumerary lumbar ribs in CD‐1 mice: Size distribution and dose response
Authors: Rogers John M. , Setzer R. Woodrow , Branch Stacy , Chernoff Neil
Published: February 2004

Supernumerary ribs (SNR) of differing sizes are commonly observed in rodent developmental toxicity studies, and the significance of treatment‐related increases in SNR in standard studies has been contentious. We induced dose‐related increases in SNR in fetal CD‐1 mice by treating on gestation days 7–8 with benomyl (BEN; 0, 75, 150 mg/kg/d), dinoseb (DIN; 0, 30, 50 mg/kg/d); 2‐methoxyethanol (2‐ME; 0, 75, 150 mg/kg/d), or valproic acid (VPA; 0, 125, 250 mg/kg/d). Incidences of SNR were 9.3–27.6% in controls and 19.3–84.4% in the high dosage groups. SNR length showed a bimodal distribution with peaks at 0.3–0.4 mm and 0.9–1.1 mm in both treated and control groups. Based on length distributions, we used an actual length of 0.6 mm to separate short (rudimentary) from long (extra) SNR. DIN, 2‐ME, and VPA induced a dose‐related increase of extra ribs, while the incidence of rudimentary ribs remained at control levels. There was no apparent correlation of the presence of either type of SNR in a fetus and the occurrence of other anomalies. These data support the idea that extra and rudimentary SNR may reflect separate developmental phenomena, and should be considered and reported separately in developmental toxicity studies for risk assessment.Birth Defects Res B 71:17–25, 2004. Published 2004 Wiley‐Liss, Inc.
Photosynthetic evolution in parasitic plants: insight from the chloroplast genome
Authors: Bungard Ralph A.
Published: February 2004

Despite the enormous diversity in plant form, structure and growth environment across the seed‐bearing plants (angiosperms and gymnosperms), the chloroplast genome has, with few exceptions, remained remarkably conserved. This conservation suggests the existence of universal evolutionary selection pressures associated with photosynthesis—the primary function of chloroplasts. The stark exceptions to this conservation occur in parasitic angiosperms, which have escaped the dominant model by evolving the capacity to obtain some or all of their carbon (and nutrients) from their plant hosts. The consequence of this evolution to parasitism is a relaxation of the evolutionary constraints associated with the need to maintain photosynthetic function, the very function that drove early stages of the ancient symbiotic relationship that produced the contemporary chloroplast. Extreme examples of reductionism among parasitic angiosperms reveals major alterations in chloroplast function with the loss of photosynthetic capacity and, with that, massive alterations in chloroplast genome content. This review highlights emerging patterns in reported gene loss and gene retention in the chloroplast genomes of parasitic plants. Some gene losses appear to occur in the early stages of parasitic evolution, even before the loss of photosynthetic capacity, like the chlororespiratory (ndh) genes. This contrasts with unexpected gene retentions, like that of the rbcL gene responsible for photosynthetic carbon dioxide fixation, and belies current understanding of gene function. The review relates gene retention to current knowledge of protein function and gene processing that has implications to broader aspects of genome conservation in organelles. BioEssays 26:235–247, 2004. Wiley Periodicals, Inc.
Notch function in the vasculature: insights from zebrafish, mouse and man
Authors: Shawber Carrie J. , Kitajewski Jan
Published: February 2004

Vascular development entails multiple cell‐fate decisions to specify a diverse array of vascular structures. Notch proteins are signaling receptors that regulate cell‐fate determination in a variety of cell types. The finding that Notch genes are robustly expressed in the vasculature suggests roles for Notch in guiding endothelial and associated mural cells through the myriad of cell‐fate decisions needed to form the vasculature. In fact, mice with defects in genes encoding Notch, Notch ligands, and components of the Notch signaling cascade invariably display vascular defects. Human Notch genes are linked to Alagille's Syndrome, a developmental disorder with vascular defects, and CADASIL, a cerebral arteriopathy. Studies in zebrafish, mice and humans indicate that Notch works in conjunction with other angiogenic pathways to pattern and stabilize the vasculature. Here, we will focus on established functions for Notch in vascular remodeling and arterial/venous specification and more speculative roles in vascular homeostasis and organ‐specific angiogenesis. BioEssays 26:225–234, 2004. © 2004 Wiley Periodicals, Inc.
Nonlinear Response Surface and Mixture Experiment Methodologies Applied to the Study of Synergism
Authors: White Donald B. , Faessel Hélène M. , Slocum Harry K. , Khinkis Leonid , Greco William R.
Published: February 2004

A new paradigm for the study of the joint action (synergism, additivity and antagonism) of different agents that combines nonlinear response surface modeling with mixture experiment methodologies is described. We achieve a global nonlinear response surface model using raw data modeling and hierarchical parameter modeling along with numerical and graphical evaluations. The method is applied to a very large previously‐published (Faesselet al., 1998)in vitrostudy of the combined effect of Trimetrexate (TMQ) and AG2034 on inhibition of cancer cell growth. The modulator Folic acid (Folate) concentration is also included as a continuous process variable. The mixture portion of the analysis is best identified as an “NLMAZ‐PV” experiment, incorporating a nonlinear mixture‐amount model with zero amounts (control observations) and the process variable. The underlying nonlinear structural model, describing the relationship between the mixture amount and the observed effect, is the four parameter Hill (1910) equation. This model for studying synergism was developed as an improvement over the flagship synergy/antagonism model of Greco et al. (1995) and other response surface synergy models. This new modeling approach allows for irregularly‐shaped isobols, complex patterns of local synergism and antagonism, a modulating agent with no effect of its own, and extensions to three or more drugs (White et al., 2003). (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Composite Hazard Functions Reflecting Competing Latent Processes
Authors: Sæbø Solve , Almøy Trygve
Published: February 2004

A method for fitting parametric models to apparently complex hazard rates in survival data is suggested. Hazard complexity may indicate competing causes of failure. A competing risks model is constructed on the assumption that a failure time can be considered as the first passage time of possibly several latent, stochastic processes competing in reaching a barrier. An additional assumption of independence between the hidden processes leads directly to a composite hazard function as the sum of the cause specific hazards. We show how this composite hazard model based on Wiener processes can serve as a flexible tool for modelling complex hazards by varying the number of processes and their starting conditions. An example with real data is presented. Parameter estimation and model assessment are based on Markov Chain Monte Carlo methods. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Optional Randomized Response Techniques for Complex Survey Designs
Authors: Arnab Raghunath
Published: February 2004

Gupta, Gupta and Singh (2002) proposed an optional randomized response (ORR) technique based on SRSWR sampling using an unrealistic assumption that the probability of providing the true/randomized response for all the individuals in a population is the same. In this paper an alternative ORR has been proposed for an arbitrary sampling design. Expressions for the estimators of the population mean, variance and unbiased estimator for the variance have been provided. It is shown that the estimator, based on an ORR, is more efficient than an estimator derived from a non‐ORR technique. Sufficient conditions for the superiority of the proposed estimator over the existing estimator provided by Gupta et al.'s (2002) have also been established. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Inference for the Ratio of Two Normal Means with Unspecified Variances
Authors: Díaz‐Francés Eloísa , Sprott David A.
Published: February 2004

Mendoza and Gutiérrez‐Peña (1999) presented a Bayesian analysis of the ratio of two normal means when the ratio of the means determines the ratio of the variances, X ∼ N(βμ, β2σ2), Y ∼ N(μ, σ2). They claimed the superiority of the Bayesian analysis, based on the whole likelihood function with non‐informative priors, by comparing it with a non‐Bayesian analysis based only on the Fieller pivotal. The purpose here is to show that the Fieller pivotal constitutes only part of the likelihood function of β in this model, so that any analysis, including Bayesian, based solely on the Fieller pivotal is highly inefficient, possibly to the extent of discarding most of the information in the sample. A non‐Bayesian analysis based on the structure of the whole likelihood function exhibits this and rectifies such an oversight. The role of the variance ratio is discussed and exemplified. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Adjusting for Ordinal Covariates by Inducing a Partial Ordering
Authors: Berger Vance W. , Zhou YanYan , Ivanova Anastasia , Tremmel Lothar
Published: February 2004

In the context of randomized clinical trials, multiplicity arises in many forms. One prominent example is when a key endpoint is measured and analyzed both at baseline and after treatment. It is common to analyze each separately, but more efficient to adjust the post‐treatment comparisons for the baseline values. Adjustment techniques generally treat the covariate (baseline value, in this case) as either nominal or continuous. Either is problematic when applied to an ordinal covariate, the former because it fails to exploit the natural ordering and the latter because it relies on an artifical notion of linear prediction and differences between values. We propose new methods for adjusting for ordinal covariates without having to treat them as nominal or continuous. Specifically, the information‐preserving composite endpoint consists of the pair of values for each patient, one at baseline and one after treatment. Some of these patterns will indicate more improvement than others, yet some pairs of patterns are not comparable. Hence, the ordering is only partial. We develop an approach to testing and deriving estimators of magnitudes of the treatment effect based on comparing each observation in one group to each observation in the other group to which it is comparable. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Structural analysis of biological aliphatic compounds using surface‐enhanced Fourier transform Raman spectroscopy
Authors: Hasegawa Takeshi
Published: February 2004

The surface‐enhanced Raman scattering (SERS) technique for Fourier transform Raman spectrometry is employed to reveal the chemical structure of biological aliphatic compounds consisting of folded, long aliphatic chains. The structural analysis is performed via the measurements of the accordion‐vibration modes generated in the ordered, long aliphatic chain. The SERS spectra after subtraction of a background spectrum give segment lengths that are almost perfectly consistent with the chemical structures studied by mass spectrometry. The agreement of the SERS results with those of mass spectrometry suggests the positions of kinks in the long hydrocarbon chain. The combination technique of SERS and mass spectrometry is useful to discuss the structure of folded, long biological lipids. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004