bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incorporating language phenotypes strengthens evidence of linkage to autism
Authors: Bradford Yuki , Haines Jonathan , Hutcheson Holli , Gardiner Marybeth , Braun Terry , Sheffield Val , Cassavant Tom , Huang Wen , Wang Kai , Vieland Veronica , Folstein Susan , Santangelo Susan , Piven Joseph 
Published: August 2002

AbstractWe investigated the effect of incorporating information about proband and parental structural language phenotypes into linkage analyses in the two regions for which we found the highest signals in our first‐stage affected sibling pair genome screen: chromosomes 13q and 7q. We were particularly interested in following up on our chromosome 7q finding in light of two prior reports of linkage of this region to developmental language disorder, since one of the diagnostic criteria for autism is absent or abnormal language development. We hypothesized that if the language phenotype were genetically relevant to linkage at the chromosome 7q locus, then incorporating parents phenotypes would increase the signal at that locus, and most of the signal would originate from the subset of families in which both probands had severe language delay. The results support these hypotheses. The linkage signals we obtained on chromosome 7q as well as at least one signal on chromosome 13q are mainly attributable to the subgroup of families in which both probands had language delay. This became apparent only when the parents’ history of language‐related difficulties was also incorporated into the analyses. Although based on our data, we were not able to distinguish between epistasis or heterogeneity models, we tentatively concluded that there may be more than one autism susceptibility locus related to language development. © 2001 Wiley‐Liss, Inc.
Human metabotropic glutamate receptor 2 gene (GRM2): Chromosomal sublocalization (3p21.1–p21.2) and genomic organization
Authors: Martí Sylvia Bort , Cichon Sven , Propping Peter , Nöthen Markus 
Published: August 2002

AbstractImbalances in glutamatergic function have been implicated in the pathogenesis of neuropsychiatric disorders. Consequently, glutamate receptors genes are promising candidates in search of susceptibility genes for these disorders. In the present study, we report the chromosomal sublocalization and genomic organization of the human metabotropic glutamate receptor 2 gene (GRM2). Using monochromosomal hybrid cell lines of NIGMS Mapping Panel 2 (Coriell Cell Repository), the GRM2 gene was localized to human chromosome 3, confirming previously reported localization. In addition, using the radiation hybrid panel RH3 (Research Genetics), we sublocalized the GRM2 gene to chromosomal region 3p21.1–p21.2. The genomic organization of the GRM2 gene was established using a premade library of adaptor‐ligated, human‐specific genomic DNA fragments. The gene consists of 5 exons, with sizes ranging from 74 to 1,076 bp. © 2001 Wiley‐Liss, Inc.
Comparison of chorionic gonadotropin expression in human and macaque (Macaca fascicularis) trophoblasts
Authors: Wilken Jason A. , Matsumoto Kikuko , Laughlin Lisa S. , Lasley Bill L. , Bedows Elliott 
Published: August 2002

AbstractWe have designed novel DNA primers that allow us to detect the expression of the subunits of chorionic gonadotropin (CG) from a variety of species of the order Primates. Using these primers, reverse transcriptase‐polymerase chain reaction (RT‐PCR), and standard cloning techniques, we detected the expression of a single gene for the common glycoprotein hormone (GPH) α‐subunit and at least two genes for the CG β‐subunit in trophoblasts of Macaca fascicularis (cynomolgous macaque (cm)) at gestational day (GD) = 26 (± 2d). No cmCG expression was detected at GD = 35–40. When sequences of cmGPH‐α and cmCG‐β genes were compared to the corresponding genes of other primates, we found that the α‐subunit of M. fascicularis was highly conserved compared to other primate species. However, cmCG β‐subunits appeared to be less conserved, residing between those of human CG‐β and baboon CG‐β when analyzed phylogenetically. Of particular interest was a three amino acid stretch in one of the expressed cmCG‐β genes that is distinct from all other primates studied. Our findings imply that not only does the expression of multiple CG β‐subunit genes appear to be common to Old World monkeys, but that the presented methodology will greatly facilitate our ability to understand primate evolution. Am. J. Primatol. 56:89–97, 2002. © 2002 Wiley‐Liss, Inc.
Assessing the accuracy of high‐resolution x‐ray computed tomography of primate trabecular bone by comparisons with histological sections
Authors: Fajardo Roberto José , Ryan T.M. , Kappelman J. 
Published: August 2002

AbstractDifferent lines of evidence suggest that trabecular bone architecture contains a functional signal related to an organism's locomotor behavior. An understanding of the interspecific and intraspecific variation in extant nonhuman primate trabecular structure is needed to evaluate its usefulness as a tool to reconstruct the locomotor habits of extinct primates. High‐resolution X‐ray computed tomography (HRXCT) is a new imaging approach with a resolution in the tens of microns that allows nondestructive access to the internal structure of bony elements. Previous studies indicate that such resolution is necessary to accurately quantify structural parameters of trabecular bone.The primary goal of this study was to test the accuracy of HRXCT by comparing stereological measurements from HRXCT images and histological thin sections of cancellous bone taken from the proximal femur and humerus of baboons. To this end, 11 bone samples were scanned on an HRXCT scanner and then thin‐sectioned to reveal the scanned plane. HRXCT images were thresholded using a modified half‐maximum height protocol. The stereological measurements included bone volume fraction (BV/TV), trabecular number (Tb.N), bone surface to volume ratio (BS/BV), trabecular thickness (Tb.Th), and trabecular spacing (Tb.Sp). The measurement errors on the HRXCT images were 10.90% for BV/TV, 6.06% for Tb.N, 14.19% for BS/BV, 14.33% for Tb.Th, and 7.09% for Tb.Sp, but none of these measurements were significantly different from the histological standards (α = 0.05).A second goal of this study was to examine the influence of thresholding, a necessary step in any morphometric study using computed tomography, on the accuracy of the quantitative morphometry. Threshold values derived from a modified half‐maximum height protocol showed that parameters derived from the region of interest (area in which stereological measurements were later taken) produced better reconstructions of the actual bone structure than threshold values derived from more inclusive areas of bone.We conclude that HRXCT can accurately reconstruct the complex architecture of trabecular bone, and that thresholding is a nontrivial step in trabecular bone studies, with even slight changes in the protocol greatly affecting the morphometric data. HRXCT represents a valuable analytical tool that should be of interest to a great many researchers in physical anthropology because it allows nondestructive access to internal morphology, thereby preserving valuable and limited skeletal collections. Am J Phys Anthropol 118:1–10, 2002. © 2002 Wiley‐Liss, Inc.
Selective hippocampal neuron loss in dementia with Lewy bodies
Authors: Harding Antony J. , Lakay Bronwyn , Halliday Glenda M. 
Published: August 2002

AbstractHippocampal volume and neuron number were measured using stereological techniques in pathologically confirmed dementia with Lewy bodies (n = 8), Parkinson's disease only (n = 4), and controls (n = 9). We, and others, have previously shown considerable cell loss in the CA1 and subiculum subregions in Alzheimer's disease. In contrast, these regions were spared in dementia with Lewy bodies where a selective loss of lower presubiculum pyramidal neurons was found. These findings suggest a selective loss of frontally projecting hippocampal neurons in dementia with Lewy bodies versus those projecting to temporal lobe regions in Alzheimer's disease.
Novel delta subunit mutation in slow‐channel syndrome causes severe weakness by novel mechanisms
Authors: Gomez Christopher M. , Maselli Ricardo A. , Vohra Bhupinder P. S. , Navedo Manuel , Stiles Joel R. , Charnet Pierre , Schott Kelly , Rojas Legier , Keesey John , Verity Anthony , Wollmann Robert W. , Lasalde‐Dominicci Jose 
Published: August 2002

AbstractWe investigated the basis for a novel form of the slow‐channel congenital myasthenic syndrome presenting in infancy in a single individual as progressive weakness and impaired neuromuscular transmission without overt degeneration of the motor endplate. Prolonged low‐amplitude synaptic currents in biopsied anconeus muscle at 9 years of age suggested a kinetic disorder of the muscle acetylcholine receptor. Ultrastructural studies at 16 months, at 9 years, and at 15 years of age showed none of the typical degenerative changes of the endplate associated with the slow‐channel congenital myasthenic syndrome, and acetylcholine receptor numbers were not significantly reduced. We identified a novel C‐to‐T substitution in exon 8 of the δ‐subunit that results in a serine to phenylalanine mutation in the region encoding the second transmembrane domain that lines the ion channel. Using Xenopus oocyte in vitro expression studies we confirmed that the δS268F mutation, as with other slow‐channel congenital myasthenic syndrome mutations, causes delayed closure of acetylcholine receptor ion channels. In addition, unlike other mutations in slow‐channel congenital myasthenic syndrome, this mutation also causes delayed opening of the channel, a finding that readily explains the marked congenital weakness in the absence of endplate degeneration. Finally, we used serial morphometric analysis of electron micrographs to explore the basis for the progressive weakness and decline of amplitude of endplate currents over a period of 14 years. We demonstrated a progressive widening and accumulation of debris in the synaptic cleft, resulting in loss of efficacy of released neurotransmitter and reduced safety factor. These studies demonstrate the role of previously unrecognized mechanisms of impairment of synaptic transmission caused by a novel mutation and show the importance of serial in vitro studies to elucidate novel disease mechanisms.
A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2–q13.1
Authors: Funayama Manabu , Hasegawa Kazuko , Kowa Hisayuki , Saito Masaaki , Tsuji Shoji , Obata Fumiya 
Published: August 2002

AbstractWe performed genomewide linkage analysis of a Japanese family with autosomal dominant parkinsonism, which exhibits clinical features compatible with those of common Parkinson's disease. Parametric two‐point linkage analysis yielded a highest log odds (LOD) score of 4.32 at D12S345 (12p11.21). Parametric multipoint linkage analysis of the 13.6cM interval around this marker yielded LOD scores almost uniformly of >4.0 with a Zmax of 4.71 at D12S85 (12q12). Haplotype analysis detected two obligate recombination events at D12S1631 and D12S339 and defined the disease‐associated haplotype in the 13.6cM interval in 12p11.2–q13.1. This haplotype was shared by all the patients and by some unaffected carriers, suggesting that disease penetration in this family is incomplete. This low penetrance suggests that environmental or other genetic factors modify expression of the disease. Nonparametric two‐point and multipoint linkage analyses, which are penetrance‐independent, yielded Zmax LOD scores of 14.2 and 24.9 at D12S345, respectively, strongly supporting the mapping of the parkinsonism locus in this family to 12p11.23–q13.11. This chromosome region is different from any known locus for hereditary parkinsonism, in keeping with the unique genetic features of the parkinsonism in this family. The nomenclature of PARK8 was assigned to the new locus.
Interferon β‐1a for early multiple sclerosis: CHAMPS trial subgroup analyses
Authors: Beck Roy W. , Chandler Danielle L. , Cole Stephen R. , Simon Jack H. , Jacobs Lawrence D. , Kinkel R. Philip , Selhorst John B. , Rose John W. , Cooper Joanna A. , Rice George , Murray Thomas J. , Sandrock Alfred W. 
Published: August 2002

AbstractThe objective of this work was to assess the effect of interferon β‐1a (Avonex®) on the rate of development of clinically definite multiple sclerosis and brain magnetic resonance imaging changes in subgroups based on type of presenting event, baseline brain magnetic resonance imaging parameters, and demographic factors in the Controlled High‐Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) trial. After the onset of a first demyelinating event, 383 patients with brain magnetic resonance imaging evidence of subclinical demyelination were treated with corticosteroids and randomly assigned to receive weekly intramuscular injections of 30μg interferon β‐1a or placebo. The treatment effect within subgroups was assessed in proportional hazards models both for the development of clinically definite multiple sclerosis and for a combined outcome of development of clinically definite multiple sclerosis or >1 new or enlarging T2 lesions on brain magnetic resonance imaging. A beneficial effect of treatment was noted in all subgroups evaluated. Adjusted rate ratios for the development of clinically definite multiple sclerosis in the optic neuritis, brainstem–cerebellar, and spinal cord syndrome subgroups were 0.58 (p = 0.05), 0.40 (p = 0.03), and 0.30 (p = 0.01) and for the development of the combined clinically definite multiple sclerosis/magnetic resonance imaging outcome were 0.50 (p < 0.001), 0.41 (p = 0.001), and 0.40 (p = 0.004), respectively. A treatment benefit on both outcome measures also was seen in subgroups based on baseline brain magnetic resonance imaging parameters, gender, and age. Interferon β‐1a is beneficial when initiated at the first clinical demyelinating event in patients with brain magnetic resonance imaging evidence of subclinical demyelination. The beneficial effect is present for optic neuritis, brainstem–cerebellar syndromes, and spinal cord syndromes.
Alzheimer's disease versus dementia with Lewy bodies: Cerebral metabolic distinction with autopsy confirmation
Authors: Minoshima Satoshi , Foster Norman L. , Sima Anders A. F. , Frey Kirk A. , Albin Roger L. , Kuhl David E. 
Published: August 2002

AbstractSeeking antemortem markers to distinguish Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), we examined brain glucose metabolism of DLB and AD. Eleven DLB patients (7 Lewy body variant of AD [LBVAD] and 4 pure diffuse Lewy body disease [DLBD]) who had antemortem position emission tomography imaging and autopsy confirmation were compared to 10 autopsy‐confirmed pure AD patients. In addition, 53 patients with clinically‐diagnosed probable AD, 13 of whom later fulfilled clinical diagnoses of DLB, were examined. Autopsy‐confirmed AD and DLB patients showed significant metabolic reductions involving parietotemporal association, posterior cingulate, and frontal association cortices. Only DLB patients showed significant metabolic reductions in the occipital cortex, particularly in the primary visual cortex (LBVAD −23% and DLBD −29% vs AD −8%), which distinguished DLB versus AD with 90% sensitivity and 80% specificity. Multivariate analysis revealed that occipital metabolic changes in DLB were independent from those in the adjacent parietotemporal cortices. Analysis of clinically‐diagnosed probable AD patients showed a significantly higher frequency of primary visual metabolic reduction among patients who fulfilled later clinical criteria for DLB. In these patients, occipital hypometabolism preceded some clinical features of DLB. Occipital hypometabolism is a potential antemortem marker to distinguish DLB versus AD.
Nanoparticles by chemical synthesis, processing to materials and innovative applications
Authors: Schmidt Helmut 
Published: August 2002

AbstractNanoparticles have been fabricated by using chemical synthesis routes under specific conditions. During a precipitation process from liquid phases, surface controlling agents (SCAs) have been added during or shortly after the formation of precipitates. These interfere with the nucleating and growing particle to avoid agglomeration and to control size. Nanoparticles from many systems have been fabricated. If the SCAs are bifunctional, the surfaces chemistry could be tailored and the zeta potential of these particles was tailored also. SiO2 particles have been used for gene targeting using this approach. In other investigations, FeO
x nanoparticles have been surface modified by amino groupings together with a sonochemical route to obtain very stable coatings. These particles have been used for in vitro tumor cell penetration and hyperthermal treatment. Boehmite nanoparticles were used to serve as condensation catalysts to prepare very hard transparent coatings for polycarbonate and an overcoat with polymerizable nanoparticles was used to produce anti‐reflective and ultrahard coatings. In systems with incorporated fluoro silanes, leading to low surface free energy coatings, nanoparticles were used to tailor the fluorine depth profile in self‐aligning transparent easy‐to‐clean coatings by influencing the critical micelle concentration. The examples show the usefulness of the chemical nanoparticle approach for nanocomposite fabrication and the high potential of these materials for medical and industrial application. Copyright © 2001 John Wiley & Sons, Ltd.
Dimethylarsinoylacetate from microbial demethylation of arsenobetaine in seawater
Authors: Khokiattiwong Somkiat , Goessler Walter , Pedersen Søren N. , Cox Raymond , Francesconi Kevin A. 
Published: August 2002

AbstractThe fate of 11 arsenic compounds in microbially enriched seawater was monitored for up to 10 days by HPLC–ICPMS. Most of the arsenicals underwent little or no change in this medium, whereas two of the compounds, arsenobetaine and arsenocholine, were completely degraded. Arsenobetaine (Me3As+CH2COO−), the predominant form of arsenic in marine animals, was transformed within hours, initially to dimethylarsinoylacetate (Me2As(O)CH2COO−) and then to dimethylarsinate (Me2As(O)O−). Arsenocholine behaved similarly but degraded at a slower rate. The identity of the new metabolite, dimethylarsinoylacetate, was confirmed by LC electrospray MS. A repeat experiment with arsenobetaine and dimethylarsinoylacetate, and employing LC electrospray MS to monitor the metabolites, produced results qualitatively identical with those from the first experiment. The rapidity of the degradation processes offers an explanation for the apparent absence of arsenobetaine in natural waters. Copyright © 2001 John Wiley & Sons, Ltd.
Determination of total mercury and monomethylmercury compounds in water samples from Minamata Bay, Japan: an interlaboratory comparative study of different analytical techniques
Authors: Logar M. , Horvat M. , Akagi H. , Ando T. , Tomiyasu T. , Fajon V. 
Published: August 2002

AbstractConcentration levels of mercury and its organic compounds in natural water samples are very low, so accurate analysis is still a major problem. To ensure the validity of such measurements a proper quality control/quality assurance programme should be implemented. In the absence of reference materials, the best way to check the accuracy of the results is through interlaboratory comparisons and comparisons of the results obtained by different analytical methods. The purpose of the present work was to compare independent analytical techniques used by two different laboratories for determination of total mercury (Hg‐T) and monomethylmercury compounds (MeHg) in seawater samples from Minamata Bay, Japan. The interlaboratory study was carried out between the Jožef Stefan Institute, Ljubljana, Slovenia and the National Institute for Minamata Disease, Minamata, Japan. Copyright © 2001 John Wiley & Sons, Ltd.
Comparison of three methods for the extraction of arsenic compounds from the NRCC standard reference material DORM‐2 and the brown alga Hijiki fuziforme
Authors: Kuehnelt Doris , Irgolic Kurt J. , Goessler Walter 
Published: August 2002

AbstractThe NRCC standard reference material DORM‐2 and the marine brown alga Hijiki fuziforme were extracted with water, methanol/water (9 + 1), and 1.5 M orthophosphoric acid. The extracts from DORM‐2 were analyzed by HPLC–ICP‐MS for arsenobetaine, arsenocholine, trimethylarsine oxide, and the tetramethylarsonium cation and the extracts from H. fuziforme for arsenous acid, arsenic acid, dimethylarsinic acid, methylarsonic acid, and four arsenoriboses. Almost no differences between the three extractants were observed when DORM‐2 was investigated. Only arsenobetaine was slightly better extracted with 1.5 M orthophosphoric acid or methanol/water (9 + 1) than with water. The sum of all extractable compounds (arsenobetaine, the tetramethylarsonium cation, and a formerly unknown compound recently identified as the trimethyl(2‐carboxyethyl)arsonium ion) accounted for 94% of the total arsenic when 1.5 M orthophosphoric acid was used, for 92% when methanol/water (9 + 1) was used, and for 87% when water was used. Significant differences in the extraction yields obtained for the alga were observed for arsenic acid and one of the arsenoriboses (‘glycerol‐ribose’). Orthophosphoric acid removed twice as much of this ribose from the algal material than water and three times more than methanol/water (9 + 1). Arsenic acid was 1.2 times better extracted with orthophosphoric acid than with water and ten times better than with methanol/water (9 + 1). Almost no differences in the extraction yields were found for dimethylarsinic acid and the other three riboses. Orthophosphoric acid extracted 76%, water 65%, and methanol/water 33% of the total arsenic from H. fuziforme. Copyright © 2001 John Wiley & Sons, Ltd.
Identification of [(GS)2AsSe]− in rabbit bile by size‐exclusion chromatography and simultaneous multielement‐specific detection by inductively coupled plasma atomic emission spectroscopy
Authors: Gailer Jürgen , Madden Sean , Buttigieg Gavin A. , Denton M. Bonner , Younis Husam S. 
Published: August 2002

AbstractAn arsenic–selenium metabolite that exhibited the same arsenic and selenium X‐ray absorption near‐edge spectra as the synthetic seleno‐bis(S‐glutathionyl) arsinium ion [(GS)2AsSe]− was recently detected in rabbit bile within 25 min after intravenous injection of rabbits with sodium selenite and sodium arsenite. X‐ray absorption spectroscopy did not (and cannot) conclusively identify the sulfur‐donor in the in vivo sample. After similar treatment of rabbits, we analyzed the collected bile samples by size‐exclusion chromatography (SEC) using inductively coupled plasma atomic emission spectroscopy (ICP‐AES) to monitor arsenic, selenium and sulfur simultaneously. The bulk of arsenic and selenium eluted in a single peak, the intensity of which was greatly increased upon spiking of the bile samples with synthethic [(GS)2AsSe]−. Hence, we identify [(GS)2AsSe]− as the major metabolite in bile after exposure of rabbits to selenite and arsenite. The reported SEC–ICP‐AES method is the first chromatographic procedure to identify this biochemically important metabolite in biological fluids and is thus a true alternative to X‐ray absorption spectroscopy, which is not available to many chemists. Copyright © 2001 John Wiley & Sons, Ltd.