bluuebunny/crossref_metadata_2025_split huggingface dataset:
The gender effect in juvenile Huntington disease patients of Italian origin
Authors: Cannella Milena , Gellera Cinzia , Maglione Vittorio , Giallonardo Patrizia , Cislaghi Giuliana , Muglia Maria , Quattrone Aldo , Pierelli Francesco , Di Donato Stefano , Squitieri Ferdinando 
Published: January 2004

AbstractWe analyzed a population of juvenile Huntington disease (HD) subjects of Italian origin (n = 57). The main aim of this study was to analyze the gender effect of the affected parent on age at onset and clinical presentation of offspring with juvenile HD. We also analyzed molecular features of the disease, including CAG mutation length and GluR6 gene polymorphism, according to the affected parent's gender. The mutation length was longer in paternally than in maternally transmitted HD juvenile patients (P = 0.025), nevertheless a similar mean early onset in the two groups (P > 0.05). This data was even enforced by that obtained from the whole cohort of patients included in the databank (n = 600) where, in the presence of increased mean parent–child CAG repeat change in paternal vs. maternal meiotic transmissions (+7.3 vs. +0.7 CAG, P = 0.0002), the mean parent–child year‐of‐onset change was similar in the two groups (−10.4 and −7.0 years, P > 0.05). A lower TAA‐triplet in GluR6 was associated with an earlier age at onset in juvenile patients (P = 0.031, R2 = 0.10). When we added the GluR6 effect on age at onset to the CAG expanded number effect (P = 0.0001, R2 = 0.68) by multiple regression approach, the coefficient of determination R2 increased to 0.81. This effect in addition to the expanded CAG repeat number, found in juvenile and not in adult patients, was slightly enforced by paternal compared to maternal transmissions (R2=0.82). Our findings suggest the occurrence of a weaker effect of the paternal mutation on juvenile age at onset in our population, possibly amplified by other genetic factors, such as the TAA‐triplet length in the GluR6 gene. © 2003 Wiley‐Liss, Inc.
Association of adverse childhood experiences, age of menarche, and adult reproductive behavior: Does the androgen receptor gene play a role?
Authors: Jorm Anthony F. , Christensen Helen , Rodgers Bryan , Jacomb Patricia A. , Easteal Simon 
Published: January 2004

AbstractPrevious research has reported associations between adverse childhood experiences, early menarche, and early sexual activity. One hypothesis to account for these findings is that an X‐linked androgen receptor GGC‐repeat polymorphism predisposes fathers to behaviors which include family abandonment and their daughters to earlier menarche and sexual activity and less stable relationships. Retrospective data relevant to this theory were examined from a community survey involving 3,702 women in the age groups 20–24, 40–44, and 60–64 years, and another involving 908 women aged 18–79 years. Earlier age of menarche was found to be associated with adverse childhood experiences and earlier sexual activity. However, the androgen receptor gene polymorphism was unrelated to adverse fathering behavior or to marital breakdown. © 2003 Wiley‐Liss, Inc.
Is the WKL1 gene associated with schizophrenia?
Authors: Kaganovich M. , Peretz A. , Ritsner M. , Bening Abu‐Shach U. , Attali B. , Navon R. 
Published: January 2004

AbstractA missense mutation Leu309Met in the WKL1 (MLC1, KIAA0027) gene, mapped to 22q13.3, was reported to co‐segregate with periodic catatonic schizophrenia (SCZ) in a single large German pedigree with seven affected individuals (Meyer et al. [2001: Mol Psychiatry 6:302–306]). This report raised the following questions that were dealt with in the present study: does the Leu309Met mutation have a role in SCZ, or only in catatonic SCZ? Does the mutation Leu309Met in the WKL1 gene, encoding a putative membrane protein, non‐selective cation channel, have any effect on the channel activity? Is the WKL1 gene, which is expressed exclusively in brain, expressed differently in SCZ brains compared to controls? These questions were answered by screening the Leu309Met mutation in 117 Israeli Jewish patients with SCZ (55 Ashkenazi and 62 non‐Ashkenazi Jews) and 176 matched controls. In search of differences in the level of WKL1 gene expression, postmortem dorsalateral prefrontal cortex of 16 schizophrenic patients and 15 controls was checked. We also measured the putative channel activity of normal WKL1 subcloned in pcDNA3 to determine the effect of the reported Leu309Met mutation. Our results argue against the involvement of WKL1 in SCZ susceptibility. © 2003 Wiley‐Liss, Inc.
The new mutation, E46K, of α‐synuclein causes parkinson and Lewy body dementia
Authors: Zarranz Juan J. , Alegre Javier , Gómez‐Esteban Juan C. , Lezcano Elena , Ros Raquel , Ampuero Israel , Vidal Lídice , Hoenicka Janet , Rodriguez Olga , Atarés Begoña , Llorens Verónica , Tortosa Estrella Gomez , del Ser Teodoro , Muñoz David G. , de Yebenes Justo G. 
Published: January 2004

AbstractFamilial parkinsonism and dementia with cortical and subcortical Lewy bodies is uncommon, and no genetic defect has been reported in the previously described sibships. We present a Spanish family with autosomal dominant parkinsonism, dementia, and visual hallucinations of variable severity. The postmortem examination showed atrophy of the substantia nigra, lack of Alzheimer pathology, and numerous Lewy bodies which were immunoreactive to α‐synuclein and ubiquitin in cortical and subcortical areas. Sequencing of the α‐synuclein gene showed a novel, nonconservative E46K mutation in heterozygosis. The E46K mutation was present in all affected family members and in three young asymptomatic subjects, but it was absent in healthy and pathological controls. The novel mutation, that substitutes a dicarboxylic amino acid, glutamic acid, with a basic amino acid such as lysine in a much conserved area of the protein, is likely to produce severe disturbance of protein function. Our data show that, in addition to the previously described hereditary α‐synucleinopathies, dementia with Lewy bodies is related to mutation of α‐synuclein.
Characterizing the diffusion/perfusion mismatch in experimental focal cerebral ischemia
Authors: Meng Xiangjun , Fisher Marc , Shen Qiang , Sotak Christopher H. , Duong Timothy Q. 
Published: January 2004

AbstractDiffusion‐weighted imaging (DWI) and perfusion‐weighted imaging (PWI) can rapidly detect lesions in acute ischemic stroke patients. The PWI volume is typically substantially larger than the DWI volume shortly after onset, that is, a diffusion/ perfusion mismatch. The aims of this study were to follow the evolution of the diffusion/ perfusion mismatch in permanent and 60‐ minute temporary focal experimental ischemia models in Sprague‐Dawley rats using the intraluminal middle cerebral artery occlusion (MCAO) method. DWI and arterial spin‐labeled PWI were performed at 30, 60, 90, 120, and 180 minutes after occlusion and lesion volumes (mm3) calculated At 24 hours after MCAO, and infarct volume was determined using triphenyltetrazolium chloride staining. In the permanent MCAO group, the lesion volume on the ADC maps was significantly smaller than that on the cerebral blood flow maps through the first 60 minutes after MCAO; but not after 90 minutes of occlusion. With 60 minutes of transient ischemia, the diffusion/perfusion mismatch was similar, but after reperfusion, the lesion volumes on ADC and cerebral blood flow maps became much smaller. There was a significant difference in 24‐ hour infarct volumes between the permanent and temporary occlusion groups.
Clinical features of cerebral cavernous malformations patients with KRIT1 mutations
Authors: Denier Christian , Labauge Pierre , Brunereau Laurent , Cavé‐Riant Florence , Marchelli Florence , Arnoult Minh , Cecillon Michaelle , Maciazek Jacqueline , Joutel Anne , Tournier‐Lasserve Elisabeth 
Published: January 2004

AbstractCerebral Cavernous Malformations (CCM/OMIM 604214) are vascular malformations causing seizures and cerebral hemorrhages. They occur as a sporadic and autosomal dominant condition, the latter being characterized by the presence of multiple CCM lesions. Stereotyped truncating mutations of KRIT1, the sole CCM gene identified so far, have been identified in CCM1 linked families but the clinical features associated with KRIT1 mutations have not yet been assessed in a large series of patients. We conducted a detailed clinical, neuroradiological and molecular analysis of 64 consecutively recruited CCM families segregating a KRIT1 mutation. Those families included 202 KRIT1 mutation carriers. Among the 202 KRIT1 mutation carriers, 126 individuals were symptomatic and 76 symptom‐free. Mean age at clinical onset was 29.7 years (range, 2–72); initial clinical manifestations were seizures in 55% of the cases and cerebral hemorrhages in 32%. Average number of lesions on T2 weighted MRI was 4.9 (±7.2) and on gradient echo sequences 19.8 (±33.2). Twenty‐six mutation carriers harbored only one lesion on T2‐weighted MRI, including 4 mutation carriers, aged from 18 to 55 yr‐old, who presented only one CCM lesion both on T2‐weighted and on highly sensitive gradient echo MRI sequences. Five symptom free mutation carriers, aged from 27 to 48 yr‐old, did not have any detectable lesion both on T2WI and gradient echo MRI sequences. Within KRIT1/CCM1 families, both clinical and radiological penetrance are incomplete and age dependent. Importantly for genetic counseling, nearly half of the KRIT1 mutation carriers aged 50 or more are symptom‐free. The presence of only one lesion, even when using gradient echo MRI sequences, can be observed in some patients with an hereditary form of the disease. Incomplete neuroradiological penetrance precludes the use of cerebral MRI to firmly establish a non carrier status, even at an adult age and even when using highly sensitive gradient echo MRI. Altogether these data suggest that the hereditary nature of the disorder may be overlooked in some mutation carriers presenting as sporadic cases with a unique lesion. Ann Neurol 2004
Presence of dendritic cells, MCP‐1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue
Authors: Henkel Jenny S. , Engelhardt Joseph I. , Siklós László , Simpson Ericka P. , Kim Seung H. , Pan Tianhong , Goodman J. Clay , Siddique Teepu , Beers David R. , Appel Stanley H. 
Published: January 2004

AbstractDendritic cells are potent antigen‐presenting cells that initiate and amplify immune responses. To determine whether dendritic cells participate in inflammatory reactions in amyotrophic lateral sclerosis (ALS), we examined mRNA expression of dendritic cell surface markers in individual sporadic ALS (sALS), familial ALS (fALS), and nonneurological disease control (NNDC) spinal cord tissues using semiquantitative and real‐time reverse transcription polymerase chain reaction (RT‐PCR). Immature (DEC205, CD1a) and activated/mature (CD83, CD40) dendritic cell transcripts were significantly elevated in ALS tissues. The presence of immature and activated/mature dendritic cells (CD1a+ and CD83+) was confirmed immunohistochemically in ALS ventral horn and corticospinal tracts. Monocytic/macrophage/microglial transcripts (CD14, CD18, SR‐A, CD68) were increased in ALS spinal cord, and activated CD68+ cells were demonstrated in close proximity to motor neurons. mRNA expressions of the chemokine MCP‐1, which attracts monocytes and myeloid dendritic cells, and of the cytokine macrophage‐colony stimulating factor (M‐CSF) were increased in ALS tissues. The MCP‐1 protein was expressed in glia in ALS but not in control tissues and was increased in the CSF of ALS patients. Those patients who progressed most rapidly expressed significantly more dendritic transcripts than patients who progressed more slowly. These results support the involvement of immune/inflammatory responses in amplifying motor neuron degeneration in ALS.
Somatic mutations in VHL germline deletion kindred correlate with mild phenotype
Authors: Wait Scott D. , Vortmeyer Alexander O. , Lonser Russell R. , Chang David T. , Finn Michael A. , Bhowmick Deb A. , Pack Svetlana D. , Oldfield Edward H. , Zhuang Zhengping 
Published: January 2004

AbstractGenerally, von Hippel–Lindau (VHL) disease is caused by a germline mutation of the VHL gene (chromosome 3p), and tumorigenesis is initiated from a “second‐hit” deletion. A subset of VHL patients have a germline deletion of the VHL gene, and the molecular events leading to tumorigenesis are not fully understood. To determine the molecular pathogenesis of tumor formation in this setting, we analyzed five central nervous system hemangioblastomas from three patients of a single VHL germline deletion kindred, all displaying mild clinical phenotype. Rather than loss of heterozygosity (the “second hit” in VHL germline mutation patients), all tumors from this kindred showed “second‐hit” point mutations on the wild‐type allele. Moreover, in two patients who each had two hemangioblastomas resected each tumor contained a unique mutation. The specific germline deletion and the overall genetic makeup of the patient did not predict these random “second‐hit” point mutations. These results suggest that in patients with germline deletion of a tumor suppressor gene there is a unique genetic mechanism underlying tumorigenesis. This unique genetic mechanism correlates with and may help to understand the mild clinical phenotype seen in these patients.
Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein
Authors: Sano Yasuteru , Date Hidetoshi , Igarashi Shuichi , Onodera Osamu , Oyake Mutsuo , Takahashi Toshiaki , Hayashi Shintaro , Morimatsu Mitsunori , Takahashi Hitoshi , Makifuchi Takao , Fukuhara Nobuyoshi , Tsuji Shoji 
Published: January 2004

AbstractEarly‐onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH) is an autosomal recessive neurodegenerative disorder characterized by early‐onset ataxia, ocular motor apraxia, and hypoalbuminemia. Recently, the causative gene for EAOH, APTX, has been identified. Of the two splicing variants of APTX mRNA, the short and the long forms, long‐form APTX mRNA was found to be the major isoform. Aprataxin is mainly located in the nucleus, and, furthermore, the first nuclear localization signal located near the amino terminus of the long‐form aprataxin is essential for its nuclear localization. We found, based on the yeast two‐hybrid and coimmunoprecipitation experiments, that the long‐form but not the short‐form aprataxin interacts with XRCC1 (x‐ray repair cross‐complementing group 1). Interestingly the amino terminus of the long‐form aprataxin is homologous with polynucleotidekinase‐3′‐phosphatase, which has been demonstrated to be involved in base excision repair, a subtype of single‐strand DNA break repair, through interaction with XRCC1, DNA polymerase β, and DNA ligase III. These results strongly support the possibility that aprataxin and XRCC1 constitute a multiprotein complex and are involved in single‐strand DNA break repair, and furthermore, that accumulation of unrepaired damaged DNA underlies the pathophysiological mechanisms of EAOH.
Cerebral palsy is characterized by protein mediators in cord serum
Authors: Kaukola Tuula , Satyaraj Ebenezer , Patel Dhavalkumar D. , Tchernev Velizar T. , Grimwade Brian G. , Kingsmore Stephen F. , Koskela Pentti , Tammela Outi , Vainionpää Leena , Pihko Helena , Äärimaa Tuula , Hallman Mikko 
Published: January 2004

AbstractCerebral palsy (CP) is a major neurodevelopmental disability in childhood. An association between intrauterine infection and CP has been reported. We examined the relationship between inflammatory mediators in cord serum and CP in term and preterm children. Regional multicenter study was conducted on 19 CP children and 19 gestation‐matched paired controls. CP children (n = 27) were further compared with controls of similar gestation at birth (n = 25). Serum levels of 78 protein mediators were analyzed. Eleven analytes correlated with the length of gestation both in cases and controls. In paired analysis, B‐lymphocyte chemoattractant, ciliary neurotrophic factor, epidermal growth factor, interleukin (IL)–5, IL‐12, IL‐13, IL‐15, macrophage migration inhibitory factor, monocyte chemoattractant protein–3, monokine induced by interferon γ, and tumor necrosis factor–related apoptosis‐inducing ligand were higher in children with CP (p ≤ 0.05). Preterm infants with CP showed higher epidermal growth factor and lower levels of granulocyte‐macrophage colony‐stimulating factor, IL‐2, macrophage‐derived chemokine, and pulmonary and activation‐regulated chemokine than their paired controls. Inflammatory mediators and growth factors serve as a footprint of the fetal response to an insult manifesting after birth as a permanent brain damage. The cytokine patterns at birth differ between premature and term infants who develop CP.
Constitutive activation of MAPK cascade in acute quadriplegic myopathy
Authors: Di Giovanni Simone , Molon Annamaria , Broccolini Aldobrando , Melcon Gisela , Mirabella Massimiliano , Hoffman Eric P. , Servidei Serenella 
Published: January 2004

AbstractAcute quadriplegic myopathy (AQM; also called “critical illness myopathy”) shows acute muscle wasting and weakness and is experienced by some patients with severe systemic illness, often associated with administration of corticosteroids and/or neuroblocking agents. Key aspects of AQM include muscle atrophy and myofilament loss. Although these features are shared with neurogenic atrophy, myogenic atrophy in AQM appears mechanistically distinct from neurogenic atrophy. Using muscle biopsies from AQM, neurogenic atrophy, and normal controls, we show that both myogenic and neurogenic atrophy share induction of myofiber‐specific ubiquitin/proteosome pathways (eg, atrogin‐1). However, AQM patient muscle showed a specific strong induction of transforming growth factor (TGF)–β/MAPK pathways. Atrophic AQM myofibers showed coexpression of TGF‐β receptors, p38 MAPK, c‐jun, and c‐myc, including phosphorylated active forms, and these same fibers showed apoptotic features. Our data suggest a model of AQM pathogenesis in which stress stimuli (sepsis, corticosteroids, pH imbalance, osmotic imbalance) converge on the TGF‐β pathway in myofibers. The acute stimulation of the TGF‐β/MAPK pathway, coupled with the inactivity‐induced atrogin‐1/proteosome pathway, leads to the acute muscle loss seen in AQM patients. Ann Neurol 2004
Deterioration of naming nouns versus verbs in primary progressive aphasia
Authors: Hillis Argye E. , Oh Sangjin , Ken Lynda 
Published: January 2004

AbstractDisproportionate impairment of naming nouns versus verbs and the opposite pattern have been reported in cases of focal brain damage or degenerative disease, indicating that processing of nouns and verbs may rely on different brain regions. However, it has not been clear whether it is the spoken word forms or the meanings (or both) of nouns and verbs that depend on separate neural regions. We tested oral and written naming of nouns and verbs, matched in difficulty, in patients with nonfluent primary progressive aphasia (nonfluent PPA; n = 15), fluent primary progressive aphasia (fluent PPA; n = 7), and amyotrophic lateral sclerosis with frontotemporal dementia (ALS‐FTD; n = 6). Patients with nonfluent PPA and ALS‐FTD, both individually and as groups, were significantly more impaired on verb naming than on noun naming and significantly more impaired on oral naming than written naming. Patients with fluent PPA showed the opposite pattern for both word class and modality, significantly more impaired naming of nouns versus verbs and significantly more impaired written versus oral naming. Results indicate that separate regions of the brain are essential for access to oral and written word forms of verbs and nouns, and that these neural regions can be differentially damaged in separate forms of PPA.
SCA17 homozygote showing Huntington's disease‐like phenotype
Authors: Toyoshima Yasuko , Yamada Mitsunori , Onodera Osamu , Shimohata Mitsuteru , Inenaga Chikanori , Fujita Nobuya , Morita Masahiro , Tsuji Shoji , Takahashi Hitoshi 
Published: January 2004

AbstractWe report a homozygous case of spinocerebellar ataxia type 17 with 48 glutamines. The age of the patient at disease onset was not lower than those of heterozygotes with the same CAG‐repeat sizes, but the clinical manifestations were rapidly progressive dementia and chorea. Neuronal loss was relatively restricted and most prominent in the Purkinje cell layer and striatum; however, intranuclear neuronal polyglutamine accumulation was widespread, with a high frequency in the cerebral cortex and striatum.
Perturbation of sphingolipid metabolism and ceramide production in HIV‐dementia
Authors: Haughey Norman J. , Cutler Roy G. , Tamara Anita , McArthur Justin C. , Vargas Diana L. , Pardo Carlos A. , Turchan Jadwiga , Nath Avindra , Mattson Mark P. 
Published: January 2004

AbstractInfection by the human immunodeficiency virus type 1 (HIV‐1) often results in neurological dysfunction including HIV dementia (HIVD). Alterations in cytokine and redox balance are thought to play important roles in the pathogenesis of HIVD, but the specific mechanisms underlying neuronal dysfunction and death are unknown. Activation of cytokine receptors and oxidative stress can induce the production of ceramide from membrane sphingomyelin, and recent findings suggest that ceramide is an important mediator of a form of programmed cell death called apoptosis. We now report that levels of ceramide, sphingomyelin, and hydroxynonenal (HNE) are significantly increased in brain tissues and cerebrospinal fluid of HIVD patients. Exposure of cultured neurons to the neurotoxic HIV proteins gp120 and Tat resulted in increased cellular levels of sphingomyelin, ceramide, and HNE. The ceramide precursor palmitoyl‐CoA sensitized neurons to Tat and gp120 toxicity, whereas an inhibitor of ceramide production reduced Tat and gp120‐induced increases of ceramide and HNE and protected the neurons from Tat and gp120‐induced death. These results suggest that HIV‐1 infection may promote a lipid imbalance in neural cells, resulting in an overproduction of ceramide and consequent cellular dysfunction and death.
Rhabdomyolysis and paraneoplastic stiff‐man syndrome with amphiphysin autoimmunity
Authors: Petzold Gabor C. , Marcucci Melissa , Butler Margaret H. , Van Landeghem Frank K. H. , Einhäupl Karl M. , Solimena Michele , Valdueza José M. , De Camilli Pietro 
Published: January 2004

AbstractStiff‐Man syndrome (SMS) is a rare disease of the central nervous system characterized by chronic muscle rigidity and autoimmunity directed against synaptic antigens. In a subset of patients, generally positive for antiamphiphysin autoantibodies, SMS has an autoimmune paraneoplastic origin. Amphiphysin isoforms are expressed at high levels in brain and skeletal muscle and often are overexpressed in breast cancer. We report here the occurrence of rhabdomyolysis in a patient with SMS, breast cancer, and antibodies that recognize both brain and muscle amphiphysin isoforms. Immunotherapy induced a remission of both rhabdomyolysis and SMS symptoms. Autoimmune rhabdomyolysis may represent a paraneoplastic complication of cancer patients with amphiphysin autoimmunity.