bluuebunny/crossref_metadata_2025_split huggingface dataset:
X‐inactivation pattern in multiple tissues from two leber's hereditary optic neuropathy (LHON) patients
Authors: Pegoraro Elena , Vettori Andrea , Valentino Maria L. , Molon Annamaria , Mostacciuolo Maria L. , Howell Neil , Carelli Valerio 
Published: April 2003

AbstractThe more frequent manifestation of ophthalmological abnormalities in males, relative to females, is an unexplained feature of Leber's hereditary optic neuropathy (LHON) that suggests an X‐linked modifying gene acting in concert with the pathogenic LHON mitochondrial DNA (mtDNA) mutation. In addition, segregation analysis of the optic neuropathy in LHON pedigrees was compatible with the presence of a recessive‐modifying gene on chromosome X. According to this two‐locus model, females would be affected only if homozygous or if they were susceptible to skewed X‐inactivation. Attempts both to localize the putative LHON‐modifying gene by linkage analysis and to find an excess of skewed X‐inactivation in affected females were unsuccessful, although the inactivation pattern was only studied in DNA isolated from blood cells. We had the opportunity to analyze a wide range of tissues at autopsy, including the optic nerves and the retina, from two LHON female patients. We found no evidence of skewed X‐inactivation in the affected tissues, thus weakening further the hypothesized involvement of a specific X chromosome locus in the pathophysiological expression of LHON. © 2003 Wiley‐Liss, Inc.
Lambert–Eaton Myasthenic syndrome in a child with an autoimmune phenotype
Authors: Hoffman William H. , Helman Sandra W. , Sekul Elizabeth , Carroll James E. , Vega Roger A. 
Published: April 2003

AbstractWe report on a child with a family history of autoimmune defects, who presented at the age of 3½ years with alopecia and Graves disease. He subsequently developed vitiligo and psoriasis. At 9½ years, he developed an autoimmune form of Lambert–Eaton Myasthenic syndrome (LEMS) with a significant elevation of glutamic acid decarboxylase (GAD) autoantibodies. Shortly thereafter he developed chronic urticaria. HLA associations were present for Graves disease, vitiligo, psoriasis, and IgA deficiency. There was also evidence of autoimmunity involving the pancreatic islet cells and gastric parietal cells. © 2003 Wiley‐Liss, Inc.
A distinctive type of metaphyseal chondrodysplasia with characteristic thickening of the distal ulna and radius: Possible metaphyseal chondrodysplasia‐rosenberg
Authors: Lee Yung‐Seng , Elliott Alison M. , Loke Kah‐Yin , Lachman Ralph S. 
Published: April 2003

AbstractWe report an 8‐year‐old boy with a distinctive form of metaphyseal chondrodysplasia (MCD). He presented with moderate disproportionate short stature and bony swelling of his wrists, knees, and ankles. There were severe metaphyseal abnormalities with a honeycomb appearance affecting the distal tibiae and fibulae, proximal tibiae, distal femurs, distal ulnae and radii, and both hands. His thoracolumbar spine was normal. Radiological examination of the mother's forearms revealed widening of the distal radii and short ulnae with hypoplastic distal ends. Rosenberg and Löhr [1986: Eur J Pediatr 145:40–45] reported a four‐generational kindred in which affected members had thickening of the wrist proximal to the styloid process of the ulna and thickening of the dorsum sellae. Although many of the radiographic features of this patient are those of MCD‐Rosenberg, the skeletal features of our patient do not appear to represent any known classified forms of MCD. © 2003 Wiley‐Liss, Inc.
Genetic approaches to polydipsia in schizophrenia: A preliminary report of a family study and an association study of an angiotensin‐converting enzyme gene polymorphism
Authors: Shinkai Takahiro , Ohmori Osamu , Hori Hiroko , Nakamura Jun 
Published: April 2003

AbstractThe pathophysiology of polydipsia in patients with schizophrenia is inadequately understood. This study aims to investigate the genetic influence on polydipsia in schizophrenia, and is comprised of a family study and an association study. First, we screened in‐patients in 14 psychiatric hospitals and found a total of 36 pairs of a proband and his/her first‐degree relative, both of whom were diagnosed with schizophrenia. Among these pairs, a significant familial concordance of polydipsia was found (Fisher's exact test, two‐sided, P = 0.0014; odds ratio, 88.20; 95% confidence interval, 7.31–1064.34). These results indicate that genetic factors may underlie the pathophysiology of polydipsia in patients with schizophrenia. Subsequently, we examined the genetic association between polydipsia/water intoxication and the angiotensin‐converting enzyme (ACE) insertion (I)/deletion (D) polymorphism in patients with chronic schizophrenia (polydipsics: n = 65; non‐polydipsics: n = 97) because several lines of evidence suggested that ACE might be involved in the development of polydipsia in schizophrenia. The D allele of ACE was found to be associated with a non‐significant trend toward an increased risk of polydipsia (P = 0.086). Furthermore, a significant allelic association was found between the D allele of ACE and water intoxication (P = 0.0392). This significance remained after the data were adjusted for confounding variables by regression analysis. These results suggest that the ACE D allele may be a risk factor for polydipsia/water intoxication in patients with schizophrenia. © 2003 Wiley‐Liss, Inc.
Association of HFE mutations with neurodegeneration and oxidative stress in Alzheimer's disease and correlation with APOE
Authors: Pulliam Joseph F. , Jennings C. Darrell , Kryscio Richard J. , Davis Daron G. , Wilson Dianne , Montine Thomas J. , Schmitt Frederick A. , Markesbery William R. 
Published: April 2003

AbstractOxidative stress enhanced by transition metals such as iron forms an attractive hypothesis for neurodegeneration in Alzheimer's Disease (AD). Iron is increased in the brain in AD, but whether this is a primary abnormality or the result of secondary accumulation is unclear. Among several genetic loci associated with AD, the locus at chromosome 6p21 contains the hereditary hemochromatosis gene HFE. To determine whether a genetic predisposition to iron accumulation is associated with AD, we evaluated three hemochromatosis‐associated HFE mutations and APOE in cognitively and histopathologically evaluated subjects with AD, mild cognitive impairment (MCI), non‐demented controls with AD‐like pathologic changes defined by Braak stage ≥ 3 (high pathology controls (HPC)), and non‐demented controls without significant histologic changes (low‐pathology controls (LPC)). In a subset, we examined ventricular (CSF) fluid F2‐isoprostane (F2‐IsoP) levels, a marker of lipid peroxidation. Seventeen subjects demonstrated homozygous or compound heterozygous HFE mutations, 13 (9.4%) in the AD/MCI group (P = 0.019 vs. LPC) and four (20%) in the HPC group (P = 0.006, P < 0.05 with Bonferroni correction vs. LPC). In contrast, the APOE4 allele frequency was increased only in the AD/MCI patients (P < 10−3 vs. HPC, P < 10−6 vs. LPC). F2‐IsoP levels were increased in AD subjects with any HFE mutation versus wild type HFE (P = 0.027). Although confirmation is required, these findings suggest that HFE mutations are associated with increased oxidative stress and Braak stage, and that HFE and APOE genotypes are different between AD patients, high pathology and low pathology controls. © 2003 Wiley‐Liss, Inc.
CHIP: Defining a dimension of the vulnerability to attention deficit hyperactivity disorder (ADHD) using sibling and individual data of children in a community‐based sample
Authors: Curran Sarah , Rijsdijk Fruhling , Martin Neilson , Marusic Katja , Asherson Philip , Taylor Eric , Sham Pak 
Published: April 2003

AbstractWe are taking a quantitative trait approach to the molecular genetic study of attention deficit hyperactivity disorder (ADHD) using a truncated case‐control association design. An epidemiological sample of children aged 5 to 15 years was evaluated for symptoms of ADHD using a parent rating scale. Individuals scoring high or low on this scale were selected for further investigation with additional questionnaires and DNA analysis. Data in studies like this are typically complicated. In the study reported on here, individuals have from 1 to 4 questionnaires completed on them and the sample is composed of a mixture of singletons and siblings. In this paper, we describe how we used a genetic hierarchical model to fit our data, together with a twin dataset, in order to estimate genetic factor loadings. Correlation matrices were estimated for our data using a maximum likelihood approach to account for missing data. We describe how we used these results to create a composite score, the heritability of which was estimated to be acceptably high using the twin dataset. This score measures a quantitative dimension onto which molecular genetic data will be mapped. © 2003 Wiley‐Liss, Inc.
HLA‐DRB genotyping in Gilles de la Tourette patients and their parents
Authors: Schoenian Sarah , König Inke , Oertel Wolfgang , Remschmidt Helmut , Ziegler Andreas , Hebebrand Johannes , Bandmann Oliver 
Published: April 2003

AbstractGilles de la Tourette syndrome (GTS) is a common neuropsychiatric disorder of unknown cause. There is, however, growing evidence that both autoimmune and genetic factors are involved in the pathogenesis of GTS. In classical autoimmune disorders such as diabetes mellitus or multiple sclerosis, genetic susceptibility is at least in part conferred by human leucocyte antigen (HLA‐) subtypes, in particular by distinct HLA‐DRB alleles. We undertook modern, PCR‐based HLA‐DRB typing in 83 trios (affected index child and both parents) to investigate whether GTS may be associated with a particular HLA‐DRB allele. The extended transmission/disequilibrium test (ETDT) was applied to analyze transmission disequilibrium for any of the 13 alleles detected. The ETDT failed to detect transmission disequilibrium for any allele at the DRB1 locus (overall allele‐wise χ2 (12) = 12.741, Monte Carlo P = 0.4998). Our results imply that the HLA‐DRB locus does not confer genetic susceptibility to GTS. © 2003 Wiley‐Liss, Inc.
Genetics of recurrent early‐onset depression (GenRED): Design and preliminary clinical characteristics of a repository sample for genetic linkage studies
Authors: Levinson Douglas F. , Zubenko George S. , Crowe Raymond R. , DePaulo Raymond J. , Scheftner William S. , Weissman Myrna M. , Holmans Peter , Zubenko Wendy N. , Boutelle Sandra , Murphy‐Eberenz Kathleen , MacKinnon Dean , McInnis Melvin G. , Marta Diana H. , Adams Philip , Sassoon Stephanie , Knowles James A. , Thomas Jo , Chellis Jennifer 
Published: April 2003

AbstractThis is an initial report on a six‐site collaborative project, Genetics of Recurrent Early‐Onset Depression (GenRED). This is a study of a large sample of families with recurrent major depressive disorder (DSM‐IV) beginning by the age 30 in probands or 40 in relatives. Evidence suggests that early onset and recurrence of depressive episodes predict substantially increased risk of depression in first‐degree relatives compared with the general population, suggesting that susceptibility genes might be mapped with this phenotype. The projected sample of 800–1,000 affected sibling pairs (ASPs) and other relatives will be studied using genome scan methods. Biological materials and blinded clinical data will be made available through the NIMH cell repository program. The sample should have good‐to‐excellent power to detect a locus associated with a 24% or greater population‐wide increase in risk to siblings. We describe 838 affected individuals from the first 305 families containing 434 independent ASPs, or 613 ASPs counting all possible pairs. The mean age at the onset was 18.5 years, with a mean of 7.3 episodes and longest episode of 655 days. Almost all subjects had experienced at least 4 weeks of depression with five or more additional symptom criteria. Frequencies of symptoms and psychiatric and medical comorbid are provided. Substance use was more common in males, and panic disorder in females. Within pairs of affected siblings, correlations were significant for age at onset, substance abuse/dependence, panic disorder, obsessive‐compulsive disorder and nicotine initiation and persistence. We replicated previously reported associations among comorbid panic disorder and social phobia, chronicity of depression and suicidal behavior. This suggests comparability of our cases to those in earlier large family studies. This dataset should prove useful for genetic studies of a highly familial form of major depressive disorder. © 2003 Wiley‐Liss, Inc.
N‐methyl‐d‐aspartate receptor NR1 subunit gene (GRIN1) in schizophrenia: TDT and case‐control analyses
Authors: Martucci Livia , Wong Albert H.C. , Trakalo Joseph , Cate‐Carter Tasha , Wong Gregory W.H. , Macciardi Fabio M. , Kennedy James L. 
Published: April 2003

AbstractThe N‐methyl‐d‐aspartate glutamate receptors (NMDAR) act in the CNS as regulators of the release of neurotransmitters such as dopamine, noradrenaline, acetylcholine, and GABA. It has been suggested that a weakened glutamatergic tone increases the risk of sensory overload and of exaggerated responses in the monoaminergic system, which is consistent with the symptomatology of schizophrenia. We studied two silent polymorphisms in GRIN1. GRIN1/1 is a G/C substitution localized on the 5′ untranslated region; GRIN1/10 is an A/G substitution localized in exon 6 of GRIN1. Minor allele frequencies in our sample were calculated to be 0.05 and 0.2 respectively. We genotyped 86 nuclear families and 91 ethnically matched case‐control pairs. Both samples were collected from the Toronto area. We tested the hypothesis that GRIN1 polymorphisms were associated with schizophrenia using the transmission disequilibrium test (TDT) and comparing allele frequencies between cases and controls. The results are as follows: GRIN1/1: χ2 = 2.19, P = 0.14; GRIN1/10: χ2 = 1.5, P = 0.22. For the case‐control sample: GRIN1/1: χ2 = 0.013, P = 0.908; GRIN1/10: χ2 = 0.544, P = 0.461. No significant results were obtained. Haplotype analyses showed a borderline significant result for the 2,1 haplotype (χ2 = 3.86, P‐value = 0.049). An analysis of variance (ANOVA) to evaluate the association between genetic makeup and age at onset was performed, with no significant results: GRIN1/1, F[df = 2] = 0.42, P‐value = 0.659; GRIN1/10, F[df = 2] = 0.16, P‐value = 0.853. We are currently collecting additional samples to increase the power of the analyses. © 2003 Wiley‐Liss, Inc.
Multiple‐primer DNA sequencing method
Authors: Gharizadeh Baback , Ghaderi Mehran , Donnelly Declan , Amini Bahram , Wallin Keng‐Ling , Nyrén Pål 
Published: April 2003

AbstractA multiple‐primer DNA sequencing approach suitable for genotyping, detection and identification of microorganisms and viruses has been developed. In this new method two or more sequencing primers, combined in a pool, are added to a DNA sample of interest. The oligonucleotide that hybridizes to the DNA sample will function as a primer during the subsequent DNA sequencing procedure. This strategy is suited for selective detection and genotyping of relevant microorganisms and samples harboring different DNA targets such as multiple variant/infected samples as well as unspecific amplification products. This method is used here in a model system for detection and typing of high‐risk oncogenic human papilloma viruses (HPVs) in samples containing multiple infections/variants or unspecific amplification products. Type‐specific sequencing primers were designed for four of the most oncogenic (high‐risk) HPV types (HPV‐16, HPV‐18, HPV‐33, and HPV‐45). The primers were combined and added to a sample containing a mixture of one high‐risk (16, 18, 33, or 45) and one or two low‐risk types. The DNA samples were sequenced by the Pyrosequencing™ technology and the Sanger dideoxy sequencing method. Correct genotyping was achieved in all tested combinations. This multiple‐sequencing primer approach also improved the sequence data quality for samples containing unspecific amplification products. The new strategy is highly suitable for diagnostic typing of relevant species/genotypes of microorganisms.
High‐throughput capillary electrophoretic method for determination of total aminothiols in plasma and urine
Authors: Lochman Pavel , Adam Tomáš , Friedecký David , Hlídková Eva , Škopková Zuzana 
Published: April 2003

AbstractIncreased interest in the analysis of aminothiols in body fluids during the last years results in a request for high‐throughput analytical methods for their determination. We report here a novel, high‐throughput method for the determination of total concentrations of biogenous aminothiols – homocysteine, cysteine, glutathione, cysteinylglycine, γ‐glutamylcysteine, and of penicilamine, mercaptopropionylglycine, and cysteamine, three compounds used to treat disorders of aminothiol metabolism in plasma and urine. Samples were reduced with tris(carboxyethyl)phosphine and labeled with 5‐(bromomethyl)fluorescein. Capillary electrophoretic separations were performed in 60 mmol/L borate – 15 mmol/L sodium dodecyl sulfate – 2‐amino‐2‐methyl‐1‐propanol, pH 10.0, with laser‐induced fluorescence detection. Analysis time was less than 2 min. The assay is linear (r > 0.999) up to 500 μmol/L. Reproducibilities of migration times (coefficient of variation, CV) were < 0.5%. Interassay repeatabilities (CV, n = 10) were 5.08% and 6.09% for 5 μmol/L addition of homocysteine and 0.60% and 3.78% for 100 μmol/L addition of cysteine in plasma and urine, respectively. Recovery values were within 94–106% and sensitivity was better than 0.19 μmol/L for all analyzed compounds. Results agreed well with a standard high‐performance liquid chromatography (HPLC) method. The diagnostic usefulness of the method has been proven on 79 samples of cystinuric patients and 12 samples of homocystinuric patients. We report here a novel method for the determination of aminothiols in body fluids by capillary electrophoresis (CE). Determination is fast and sensitive enough for diagnostic purposes.
Numerical calculation of the electroosmotic flow at the cross region in microfluidic chips
Authors: Jin Ya , Luo Guo‐An 
Published: April 2003

AbstractA numerical study is presented for the electroosmotic flow (EOF) at the cross region in microfluidic chips. The distributions of the electric potential due to the electric double layer (EDL) and the external electric field are discussed and the calculation of the latter can give rough speculations on the flow tendencies in the channels during various operation modes. Simplification of the two‐dimensional Navier‐Stokes (N‐S) equations is obtained by focusing on the solution of interior flows, and the numerical calculation results show good agreement with the experimental images. The sample leakage to the separation channel during the “float” sampling proved to be caused not only by the sample diffusion, but also by the weak extension of the sampling electric field. It is also verified that with suitable voltage configuration, the “pinch” sampling mode is better than the “float” mode in sample plug control.
Normal human dermal fibroblasts: Proteomic analysis of cell layer and culture medium
Authors: Boraldi Federica , Bini Luca , Liberatori Sabrina , Armini Alessandro , Pallini Vitaliano , Tiozzo Roberta , Ronchetti Ivonne Pasquali , Quaglino Daniela 
Published: April 2003

AbstractProteins present within the cell layer and those released in the cell medium from in vitro cultured normal human dermal fibroblasts were separated and characterized in terms of their isoelectric point and molecular weight, by two‐dimensional (2‐D) gel electrophoresis. All spots in the synthetic gel were firstly analyzed by the Melanie 3 software and compared with those of breast cancer cells, colorectal epithelial cells, HL60, lymphoma cells, and platelets, already available on‐line. From the identification of 144 spots from both the cell layer and the medium, we were able to recognize 89 different proteins, since a certain number of spots represented different isoforms of the same molecule. Identifications were performed by matching with on‐line 2‐D databases, and by matrix assisted laser‐desorption/ionization‐time of flight‐mass spectrometry (MALDI‐TOF‐MS), in order to confirm the identification by matching, or to identify new proteins. The procedure we used allows (i) to design a highly reproducible reference map of the proteome of adult human normal fibroblasts in culture, (ii) to evaluate protein species produced in the cell layer as well as those released in the culture medium, and (iii) to compare data from gel matching with those obtained by MS. This work represents an essential step for a better knowledge of mesenchymal cells, given the widespread use of this cell type in both clinical and experimental investigations.
Identification of a specifically expressed modified form of novel PSP‐94 protein in the secretion of benign prostatic hyperplasia
Authors: Xu Kexin , Wang Xianghong , Ling Ming‐tat , Lee Davy T. W. , Fan Tianyong , Chan Franky L. , Xuan James J. W. , Tsao Sai‐Wah , Wong Yong‐Chuan 
Published: April 2003

AbstractUsing two‐dimensional gel electrophoresis, we investigated the profile of prostatic secretory proteins in human expressed prostatic secretion (EPS) from benign prostate hyperplasia (BPH) patients and compared the patterns with normal controls. We identified three specifically expressed proteins, including prostate secretory protein 61 (PSP61), in EPS from benign BPH patients but absent in normal controls. In addition, we found that PSP61 was a modified isoform of the well‐documented PSP‐94, which had a perfect matching (100% homology) to the first 61 amino acids of the PSP‐94 protein but with a deleted C‐terminus. This shortened PSP61 was not due to alternative splicing of the PSP‐94 gene at transcription level. Our results provide first evidence on the possibility of using PSP61 as a specific biological marker for diagnosis of BPH.
New archaeo‐stratigraphic data for the TD6 level in relation to Homo antecessor (Lower Pleistocene) at the site of Atapuerca, north‐central Spain
Authors: Canals Antoni , Vallverdú Josep , Carbonell Eudald 
Published: April 2003

AbstractThe sediments of the TD6 level of Gran Dolina Cave at Sierra de Atapuerca, Burgos, Spain, consist of a series of mud flows with angular clasts. The TD6 deposit has two parts: an upper part, known as the Aurora stratum, which yields Homo antecessor remains, and a lower part with rather homogeneous sediment. The excavation of TD6 level did not reveal a sequence of diachronic occupations. Instead, the contextual and stratigraphic studies permitted us to describe and delimit the micro‐units forming the TD6 deposit. The study of the distribution of archaeological remains based on vertical archaeological profiles, using an archaeo‐stratigraphic method, allowed us to document the occurrence of a series of archaeological levels within the apparent homogeneous deposit. Variations in the density of archaeological remains along the archaeo‐stratigraphic levels permitted us to define two occupational cycles in TD6. These cycles seemingly show increased activities through time, culminating in the Aurora level with the presence of cannibalized Homo antecessor remains. © 2003 Wiley Periodicals, Inc.