bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity for congenital generalized lipodystrophy in seventeen patients from Oman
Authors: Rajab Anna , Heathcote Kirsten , Joshi Surendra , Jeffery Steve , Patton Michael 
Published: October 2002

AbstractSeventeen children with congenital generalized lipodystrophy or Berardinelli‐Seip Congenital Lipodystrophy (BSCL) from 12 consanguineous sibships were observed in Oman. All children had widespread absence of adipose tissue from infancy together with apparent muscle hypertrophy and hepatomegaly. They did not appear to represent a single homogenous entity, and it was possible to subclassify the cases into two distinct groups. In the first group of seven cases, the features were similar to other published cases with acanthosis nigricans, raised insulin levels, and insulin resistance. In this group, there was an association between the degree of acanthosis nigricans and the severity of the disorder. Molecular analysis of these cases showed homozygosity at the BSCL2 locus on chromosome 11q13 in four of the seven cases. In the second group of ten cases, there were striking abnormalities in both skeletal and nonskeletal muscle. Reduced exercise tolerance and percussion myoxedema were observed in skeletal muscle, while infantile hypertrophic pyloric stenosis, prominent veins (phlebomegaly), disturbance of cardiac rhythm, and cardiomyopathy were observed in nonskeletal muscle. There was evidence against homozygosity in some cases for the known loci for BSCL, and this group may represent a new clinical syndrome with lipodystrophy at a different genetic location. © 2002 Wiley‐Liss, Inc.
No evidence for phenotypic variation between probands in case‐control versus family‐based association studies of schizophrenia
Authors: Malhotra Anil K. , Bates John A. , Jaeger Judith , Petrides Georgios , Robinson Delbert G. , Bilder Robert M. , Nassauer Katharine W. 
Published: October 2002

AbstractTraditional case‐control genetic association studies utilizing unrelated probands are often used interchangeably with family‐based designs to detect genes for complex psychiatric disorders. This strategy may be limited, however, if significant phenotypic variation exists between probands enrolled in these two types of studies. The present study compared 37 probands enrolled in a case‐control study of schizophrenia with 37 age‐, sex‐, and ethnically matched probands enrolled in a family‐based study of schizophrenia. Age of onset of illness was compared as well as performance on a battery of cognitive tests assessing attention, working memory, executive function, and verbal memory. Results revealed no significant differences in age of onset between the two groups or on any measure of cognitive performance. These data do not support reports of significant phenotypic variation between probands in case‐control and family‐based studies, and suggest that studies utilizing family‐based approaches may be used to replicate reports of association made with case‐control designs in schizophrenia. © 2002 Wiley‐Liss, Inc.
Severe lymphedema, intestinal lymphangiectasia, seizures and mild mental retardation: Further case of Hennekam syndrome with a severe phenotype
Authors: Forzano F. , Faravelli F. , Loy A. , Di Rocco M. 
Published: October 2002

AbstractWe report on an Italian patient affected by severe lymphedema of lower limbs, genitalia and face, intestinal lymphangiectasia, seizures, and moderate mental retardation. He has a flat face, flat nasal bridge, and hypertelorism. We propose that he presents with a severe form of Hennekam syndrome. © 2002 Wiley‐Liss, Inc.
Genome‐wide linkage analysis of families with obsessive‐compulsive disorder ascertained through pediatric probands
Authors: Hanna Gregory L. , Veenstra‐VanderWeele Jeremy , Cox Nancy J. , Boehnke Michael , Himle Joseph A. , Curtis George C. , Leventhal Bennett L. , Cook Edwin H. 
Published: October 2002

AbstractThe goal of this study was to identify chromosomal regions likely to contain susceptibility alleles for early‐onset obsessive‐compulsive disorder (OCD). A genome scan was done in 56 individuals from seven families ascertained through pediatric OCD probands; 27 of the 56 subjects had a lifetime diagnosis of definite OCD. Denser mapping of regions on chromosomes 2, 9, and 16 was subsequently done with those subjects and ten additional subjects from the largest family in the study. Direct interviews were completed with 65 of the 66 genotyped individuals. Relatives were interviewed blind to proband status. Of the 65 interviewed individuals, 32 had a lifetime diagnosis of definite OCD. Three of the seven probands had a history of Tourette disorder. Two of the 25 relatives with OCD had a tic history, whereas none of the 33 relatives without OCD had tics. The genome scan consisted of 349 microsatellite markers with an average between‐marker distance of 11.3 centiMorgan (cM). Fine mapping was done with 24 additional markers at an average spacing of 1.6 cM. Parametric and nonparametric linkage analyses were conducted using GENEHUNTER+. The maximum multipoint LOD score with a dominant model was 2.25 on 9p. However, with fine mapping and additional subjects, that LOD score decreased to 1.97. The maximum multipoint nonparametric LOD* score was 1.73 on 19q. The maximum multipoint LOD score with a recessive model was 1.40 on 6p. The results provide suggestive evidence for linkage on 9p and identify regions requiring further study with much larger samples. © 2002 Wiley‐Liss, Inc.
Familial childhood onset neuropathy and cirrhosis with the 4977bp mitochondrial DNA deletion
Authors: McDonald D.G.M. , McMenamin J.B. , Farrell M.A. , Droogan O. , Green A.J. 
Published: October 2002

AbstractThe common 4977 base pair mitochondrial deletion has been identified in association with a number of distinct clinical phenotypes. These include the Kearns‐Sayre syndrome, the Pearson marrow‐pancreas syndrome, and chronic progressive external ophthalmoplegia. We report the clinical and pathological findings in two siblings in whom the 4977 base pair mitochondrial DNA deletion was identified in muscle‐derived mitochondrial DNA. One sibling manifested early onset liver and renal failure, and both developed prominent peripheral sensorimotor neuropathy. These clinical findings have not been previously described in association with the 4977bp mtDNA deletion and thus represent a further expansion of the spectrum of mitochondrial disease. © 2002 Wiley‐Liss, Inc.
Further delineation of cardiac abnormalities in Costello syndrome
Authors: Lin Angela E. , Grossfeld Paul D. , Hamilton Robert M. , Smoot Leslie , Gripp Karen W. , Proud Virginia , Weksberg Rosanna , Wheeler Patricia , Picker Jonathan , Irons Mira , Zackai Elaine , Marino Bradley , Scott Charles I. , Nicholson Linda 
Published: October 2002

AbstractWe review the cardiac abnormalities in 94 patients (27 new, 67 literature) with Costello syndrome, an increasingly recognized syndrome consisting of increased birth weight, postnatal growth retardation, and distinctive facial, skin, and musculoskeletal features (MIM 218040). A cardiac abnormality was found in 59 (63%) patients, with each of three categories occurring in approximately one‐third of patients. A cardiovascular malformation (CVM) was noted in 30%, typically pulmonic stenosis (46% of those with a CVM). Cardiac hypertrophy was reported in 34%, which involved the left ventricle in 50% and was usually consistent with classic hypertrophic cardiomyopathy (HCM). A variety of rhythm disturbances were reported in 33%. Most (74%) were atrial tachycardia that was reported as supraventricular, chaotic, multifocal, or ectopic. Of 31 patients with a rhythm abnormality, 22 (68%) had an additional abnormality, i.e., CVM (4), cardiac hypertrophy (12), or both (6). Nine patients had isolated dysrhythmia, five (56%) of whom died. All of the 12 (13%) patients who died had a cardiac abnormality. One patient died of embryonal rhabdomyosarcoma, but in the remainder, a cardiac cause of death could not be disproved. All patients with Costello syndrome need a baseline cardiology evaluation with echocardiography and Holter monitoring. Additional prospective evaluations, even in patients without apparent cardiac abnormalities, would be prudent, although data are insufficient to propose a specific schedule. © 2002 Wiley‐Liss, Inc.
Linkage of chromosome 13q32 to schizophrenia in a large veterans affairs cooperative study sample
Authors: Faraone Stephen V. , Skol Andrew D. , Tsuang Debby W. , Bingham Stephen , Young Keith A. , Prabhudesai Sarita , Haverstock Susan L. , Mena Felicitas , Menon Aerath Sri Kumar , Bisset Darren , Pepple John , Sautter Fred , Baldwin Charlene , Weiss David , Collins Joseph , Keith Tim , Boehnke Michael , Tsuang Ming T. , Schellenberg G.D. 
Published: October 2002

AbstractSeveral prior reports have suggested that chromosomal region 13q32 may harbor a schizophrenia susceptibility gene. In an attempt to replicate this finding, we assessed linkage between chromosome 13 markers and schizophrenia in 166 families, each with two or more affected members. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Studies Program, included 392 sampled affected subjects and 216 affected sib pairs. By DSM‐III‐R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizoaffective disorder, depressed. The families had mixed ethnic backgrounds. The majority were northern European‐American families (n = 62, 37%), but a substantial proportion were African‐American kindreds (n = 60, 36%). Chromosome 13 markers, spaced at intervals of approximately 10 cM over the entire chromosome and 2–5 cM for the 13q32 region were genotyped and the data analyzed using semi‐parametric affected only linkage analysis. For the combined sample (with race broadly defined and schizophrenia narrowly defined) the maximum LOD score was 1.43 (Z‐score of 2.57; P = 0.01) at 79.0 cM between markers D13S1241 (76.3 cM) and D13S159 (79.5 cM). Both ethnic groups showed a peak in this region. The peak is within 3 cM of the peak reported by Brzustowicz et al. [1999: Am J Hum Genet 65:1096–1103]. © 2002 Wiley‐Liss, Inc.
DRD4 and novelty seeking: Results of meta‐analyses
Authors: Schinka J.A. , Letsch E.A. , Crawford F.C. 
Published: October 2002

AbstractStudies of the association between polymorphisms within and near the dopamine D4 receptor (DRD4) gene and novelty seeking (NS) have produced inconsistent results, raising questions about the strength of the relationship and the methodological conditions under which the relationship holds. We conducted three meta‐analyses of existing studies to provide formal statistical measures of the strength of the DRD4‐NS relationship. Results provided no support for a relationship between NS and the presence of the 7‐repeat allele of the VNTR polymorphism. A small positive effect, however, was found for long repeats of the same polymorphism. The most promising findings were obtained for the relationship with the −521 C/T promoter polymorphism, for which the analysis showed an effect size of 0.32. The positive findings are consistent with a polygenic model of influence on fundamental personality dimensions. © 2002 Wiley‐Liss, Inc.
Mitochondria, oxygen free radicals, and apoptosis
Authors: Raha Sandeep , Robinson Brian H. 
Published: October 2002

AbstractReactive oxygen species (ROS) generated by mitochondria are produced as by‐products of normal oxidative metabolism. The fate of these species is governed by a number of factors that vary from tissue to tissue in mammals and may be involved in the pathogenesis of disease. Reactive oxygen species are also invoked as agents that are important in the processes which become active in cells undergoing apoptosis. Integration of knowledge surrounding these different aspects of ROS generation is difficult and reveals considerable gaps in our understanding. © 2001 Wiley‐Liss, Inc.
Genetic drift and gene flow in a prehistoric population of the Azapa valley and coast, Chile
Authors: Varela Héctor Hugo , Cocilovo Jose Alberto 
Published: October 2002

AbstractThe present paper studies the evolutionary process operating on prehistoric groups from the Azapa valley and coast (northern Chile). The sample consists of 237 crania from the Archaic Late, Early Intermediate, Middle, Late Intermediate, and Late periods. Six metric variables were used, which were transformed to eliminate the special environmental component and to increase the proportion of genetic variance. Population structure was assessed using a method based on quantitative genetic theory, which predicts a lineal relationship between average within‐group phenotypic variance and group distance to the population centroid. Results indicate that 17.5% of the total variance accounts for special environmental variance. An excess in extraregional genetic flow is observed in the population corresponding to the Early Intermediate period in the valley. A reduced differentiation is observed between Archaic and Early Intermediate coastal groups, as well as between the latter and the inhabitants of the valley in the same period. Genetic differences between both areas increased substantially since the Middle period. Evidence indicates that long‐range gene flow was lower on the coast than in the valley, the lowest estimated Fst being 0.0199 for the total population (coast and valley), 0.0111 for the coastal population, and 0.0057 for the valley. Results are discussed in terms of regional archeological and ethnohistorical evidence, and a microevolutionary model is presented to account for the biological history of the population. Am J Phys Anthropol 118:259–267, 2002. © 2002 Wiley‐Liss, Inc.
Alzheimer's neurofibrillary pathology and the spectrum of cognitive function: Findings from the Nun Study
Authors: Riley Kathryn P. , Snowdon David A. , Markesbery William R. 
Published: October 2002

AbstractThe development of interventions designed to delay the onset of dementia highlights the need to determine the neuropathologic characteristics of individuals whose cognitive function ranges from intact to demented, including those with mild cognitive impairments. We used the Braak method of staging Alzheimer's disease pathology in 130 women ages 76–102 years who were participants in the Nun Study, a longitudinal study of aging and Alzheimer's disease. All participants had complete autopsy data and were free from neuropathologic conditions other than Alzheimer's disease lesions that could affect cognitive function. Findings showed a strong relationship between Braak stage and cognitive state. The presence of memory impairment was associated with more severe Alzheimer's disease pathology and higher incidence of conversion to dementia in the groups classified as having mild or global cognitive impairments. In addition to Braak stage, atrophy of the neocortex was significantly related to the presence of dementia. Our data indicate that Alzheimer's neurofibrillary pathology is one of the neuropathologic substrates of mild cognitive impairments. Additional studies are needed to help explain the variability in neuropathologic findings seen in individuals whose cognitive performance falls between intact function and dementia.
A novel D104G mutation in the adenine nucleotide translocator 1 gene in autosomal dominant progressive external ophthalmoplegia patients with mitochondrial DNA with multiple deletions
Authors: Komaki Hirofumi , Fukazawa Toshiyuki , Houzen Hideki , Yoshida Kazuto , Nonaka Ikuya , Goto Yu‐Ichi 
Published: October 2002

AbstractAutosomal dominant progressive external ophthalmoplegia is a mitochondrial disorder characterized by multiple large deletions of mitochondrial DNA. A recent study showed pathogenic heterozygous missense mutations in the heart/skeletal muscle isoform of the adenine nucleotide translocator 1 gene in autosomal dominant progressive external ophthalmoplegia patients. In one Japanese autosomal dominant progressive external ophthalmoplegia family, we found a novel A‐to‐G heterozygous mutation at nucleotide 311 of the adenine nucleotide translocator 1 gene, which segregated with affected individuals and could not be detected in the genomic DNA sequence of 120 normal controls. This mutation converted a highly conserved aspartic acid into a glycine at codon 104. Polymerase chain reaction analysis of single muscle fibers showed the presence of one type of deletion in each fiber, suggesting clonal expansion of mitochondrial DNA with deletions. These findings support the pathogenesis of the adenine nucleotide translocator 1 gene mutation in human disease.
Focal cortical dysplasia of Taylor's balloon cell type: Mutational analysis of the TSC1 gene indicates a pathogenic relationship to tuberous sclerosis
Authors: Becker Albert J. , Urbach Horst , Scheffler Björn , Baden Thomas , Normann Sabine , Lahl Rainer , Pannek Heinz W. , Tuxhorn Ingrid , Elger Christian E. , Schramm Johannes , Wiestler Otmar D. , Blümcke Ingmar 
Published: October 2002

AbstractFocal cortical dysplasia (FCD) is characterized by a localized malformation of the neocortex and underlying white matter. Balloon cells, similar to those observed in tuberous sclerosis, are present in many cases (FCDbc). In these patients, a hyperintense funnel‐shaped subcortical lesion tapering toward the lateral ventricle was the characteristic finding on fluid‐attenuated inversion recovery magnetic resonance imaging scans. Surgical lesionectomy results in complete seizure relief. Although the pathogenesis of FCDbc remains uncertain, histopathological similarities indicate that FCDbc may be related pathogenetically to tuberous sclerosis. Here, we studied alterations of the TSC1 and TSC2 genes in a cohort of patients with chronic, focal epilepsy and histologically documented FCDbc (n = 48). DNA was obtained after microdissection and laser‐assisted isolation of balloon cells, dysplastic neurons, and nonlesional cells from adjacent normal brain tissue. Sequence alterations resulting in amino acid exchange of the TSC1 gene product affecting exons 5 and 17 and silent base exchanges in exons 14 and 22 were increased in patients with FCDbc compared with 200 control individuals (exon 5, 2.3% FCDbc vs 0% C; exon 17, 35% FCDbc vs 1.0% C; exon 14, 37.8% FCDbc vs 15% C; exon 22, 45% FCDbc vs 23.8% C). Sequence alterations could be detected in FCDbc and in adjacent normal cells. In 24 patients, DNA was suitable to study loss of heterozygosity at the TSC1 gene locus in microdissected FCDbc samples compared with control tissue. Eleven FCDbc cases exhibited loss of heterozygosity. In the TSC2 gene, only silent polymorphisms were detected at similar frequencies as in controls. Our findings indicate that FCDbc constitutes a clinicopathological entity with distinct neuroradiological, neuropathological, and molecular genetic features. These data also suggest a role of the TSC1 gene in the development of FCDbc and point toward a pathogenic relationship between FCDbc and the tuberous sclerosis complex.
Pallidal stimulation for Parkinsonism: Improved brain activation during sequence learning
Authors: Fukuda Masafumi , Ghilardi Maria Felice , Carbon Maren , Dhawan Vijay , Ma Yilong , Feigin Andrew , Mentis Marc J. , Ghez Claude , Eidelberg David 
Published: October 2002

AbstractWe used 15O‐labeled water and positron emission tomography to assess the effect of deep brain stimulation of the internal globus pallidus on motor sequence learning in Parkinson's disease. Seven right‐handed patients were scanned on and off stimulation while they were performing a motor sequence learning task and a kinematically matched motor execution reference task. The scans were performed after a 12‐hour medication washout. Stimulation parameters were adjusted for maximal motor improvement; experimental task parameters were held constant across stimulation conditions. Internal globus pallidus stimulation improved motor ratings by 37% (p < 0.01). During the sequence learning task, stimulation improved performance as measured by several correct anticipatory movements (p < 0.01) and by verbal report (p < 0.001). Concurrent positron emission tomography imaging during learning demonstrated significant (p < 0.01) increases in brain activation with stimulation in the left dorsolateral prefrontal cortex, bilaterally in premotor cortex, and in posterior parietal and occipital association areas. Stimulation did not affect the activity of these regions during the performance of the motor execution reference task. These findings suggest that internal globus pallidus deep brain stimulation can enhance the activity of prefrontal cortico‐striato‐pallidothalamic loops and related transcortical pathways. Improved sequence learning with stimulation may be directly related to these functional changes.
Early inflammation and dementia: A 25‐year follow‐up of the Honolulu‐Asia aging study
Authors: Schmidt Reinhold , Schmidt Helena , Curb J. David , Masaki Kamal , White Lon R. , Launer Lenore J. 
Published: October 2002

AbstractInflammatory responses are associated with cardiovascular disease and may be associated with dementing disease. We evaluated the long‐term prospective association between dementia and high‐sensitivity C‐reactive protein, a nonspecific marker of inflammation. Data are from the cohort of Japanese American men who were seen in the second examination of the Honolulu Heart Program (1968–1970) and subsequently were reexamined 25 years later for dementia in the Honolulu‐Asia Aging Study (1991–1996). In a random subsample of 1,050 Honolulu‐Asia Aging Study cases and noncases, high‐sensitivity C‐reactive protein concentrations were measured from serum taken at the second examination; dementia was assessed in a clinical examination that included neuroimaging and neuropsychological testing and was evaluated using international criteria. Compared with men in the lowest quartile (<0.34mg/L) of high‐sensitivity C‐reactive protein, men in the upper three quartiles had a 3‐fold significantly increased risk for all dementias combined, Alzheimer's disease, and vascular dementia. For vascular dementia, the risk increased with increasing quartile. These relations were independent of cardiovascular risk factors and disease. These data support the view that inflammatory markers may reflect not only peripheral disease, but also cerebral disease mechanisms related to dementia, and that these processes are measurable long before clinical symptoms appear.