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System Abnormalities (system + abnormality)
Kinds of System Abnormalities Selected AbstractsRole of the Rap1 GTPase in astrocyte growth regulationGLIA, Issue 3 2003Anthony J. Apicelli Abstract Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome in which affected individuals develop nervous system abnormalities that might reflect astrocyte dysfunction. The TSC2 gene product, tuberin, encodes a GTPase-activating protein (GAP) domain, which regulates the activity of Rap1 in vitro. To determine whether dysregulated Rap1, resulting from TSC2 inactivation, leads to increased astrocyte proliferation in vivo, we generated transgenic mice expressing activated Rap1G12V specifically in astrocytes. We observed no statistically significant difference in the number of astrocytes between wild-type and GFAP-Rap1G12V littermates in vivo; however, during log-phase growth, we observed a 25% increase in GFAP-Rap1G12V astrocyte doubling times compared to wild-type controls. This decreased proliferation was associated with delayed MAP kinase, but not AKT, activation. Lastly, to determine whether constitutive Rap1 activation could reverse the increased astrocyte proliferation observed in transgenic mice expressing oncogenic RasG12V, we generated transgenic mice expressing both RasG12V and Rap1G12V in astrocytes. These double transgenic mice showed a striking reversion of the RasG12V astrocyte growth phenotype. Collectively, these results argue that the tumor suppressor properties of tuberin are unlikely to be related to Rap1 inactivation and that Rap1 inhibits mitogenic Ras pathway signaling in astrocytes. GLIA 42:225,234, 2003. © 2003 Wiley-Liss, Inc. [source] The Nutrition, Aging, and Memory in Elders (NAME) study: design and methods for a study of micronutrients and cognitive function in a homebound elderly populationINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 6 2006Tammy M. Scott Abstract Background Micronutrient status can affect cognitive function in the elderly; however, there is much to learn about the precise effects. Understanding mediating factors by which micronutrient status affects cognitive function would contribute to elders' quality of life and their ability to remain in the home. Objectives The Nutrition, Aging, and Memory in Elders (NAME) Study is designed to advance the current level of knowledge by investigating potential mediating factors by which micronutrient status contributes to cognitive impairment and central nervous system abnormalities in the elderly. NAME targets homebound elders because they are understudied and particularly at risk for poor nutritional status. Methods Subjects are community-based elders aged 60 and older, recruited through area Aging Services Access Points. The NAME core data include demographics; neuropsychological testing and activities of daily living measures; food frequency, health and behavioral questionnaires; anthropometrics; gene status; plasma micronutrients, homocysteine, and other blood determinants. A neurological examination, psychiatric examination, and brain MRI and volumetric measurements are obtained from a sub-sample. Results Preliminary data from first 300 subjects are reported. These data show that the NAME protocol is feasible and that the enrolled subjects are racially diverse, at-risk, and had similar basic demographics to the population from which they were drawn. Conclusion The goal of the NAME study is to evaluate novel relationships between nutritional factors and cognitive impairment. These data may provide important information on potential new therapeutic strategies and supplementation standards for the elderly to maintain cognitive function and potentially reduce the public health costs of dementia. Copyright © 2006 John Wiley & Sons, Ltd. [source] Mitochondrial DNA mutations as a fundamental mechanism in physiological declines associated with agingAGING CELL, Issue 1 2003Jeong W. Pak Summary The hypothesis that mitochondrial DNA damage accumulates and contributes to aging was proposed decades ago. Only recently have technological advancements, which facilitate microanalysis of single cells or portions of cells, revealed that mtDNA deletion mutations and, perhaps, single nucleotide mutations accumulate to physiologically relevant levels in the tissues of various species with age. Although a link between single nucleotide mutations and physiological consequences in aging tissue has not been established, the accumulation of deletion mutations in skeletal muscle fibres has been associated with sarcopenia. Different, and apparently random, deletion mutations are specific to individual fibres. However, the mtDNA deletion mutation within a phenotypically abnormal region of a fibre is the same, suggesting a selection, amplification and clonal expansion of the initial deletion mutation. mtDNA deletion mutations within a muscle fibre are associated with specific electron transport system abnormalities, muscle fibre atrophy and fibre breakage. These data point to a causal relationship between mitochondrial DNA mutations and the age-related loss of muscle mass. [source] Levodopa treatment reverses endocannabinoid system abnormalities in experimental parkinsonismJOURNAL OF NEUROCHEMISTRY, Issue 4 2003Mauro Maccarrone Abstract Cannabinoid receptors and their endogenous ligands are potent inhibitors of neurotransmitter release in the brain. Here, we show that in a rat model of Parkinson's disease induced by unilateral nigral lesion with 6-hydroxydopamine (6-OHDA), the striatal levels of the endocannabinoid anandamide (AEA) were increased, while the activity of its membrane transporter and hydrolase (fatty-acid amide hydrolase, FAAH) were decreased. These changes were not observed in the cerebellum of the same animals. Moreover, the frequency and amplitude of glutamate-mediated spontaneous excitatory post-synaptic currents were augmented in striatal spiny neurones recorded from parkinsonian rats. Remarkably, the anomalies in the endocannabinoid system, as well as those in glutamatergic activity, were completely reversed by chronic treatment of parkinsonian rats with levodopa, and the pharmacological inhibition of FAAH restored a normal glutamatergic activity in 6-OHDA-lesioned animals. Thus, the increased striatal levels of AEA may reflect a compensatory mechanism trying to counteract the abnormal corticostriatal glutamatergic drive in parkinsonian rats. However, this mechanism seems to be unsuccessful, since spontaneous excitatory activity is still higher in these animals. Taken together, these data show that anomalies in the endocannabinoid system induced by experimental parkinsonism are restricted to the striatum and can be reversed by chronic levodopa treatment, and suggest that inhibition of FAAH might represent a possible target to decrease the abnormal cortical glutamatergic drive in Parkinson's disease. [source] Inhibition of Hematopoietic Progenitor Cell Proliferation by Ethanol in Human Immunodeficiency Virus Type 1 Tat-Expressing Transgenic MiceALCOHOLISM, Issue 3 2001Om Prakash Background: A number of hematological abnormalities are associated with both human immunodeficiency virus type 1 (HIV-1) infection and alcohol abuse. There is little information on how alcohol abuse might further influence the survival and growth of hematopoietic progenitors in HIV-infected individuals in the presence of immune system abnormalities and anti-HIV drugs. Because there is evidence that viral transactivator Tat itself can induce hematopoietic suppression, in this study we examined the role of ethanol as a cofactor in transgenic mice that expressed HIV-1 Tat protein. Methods: Tat transgenic mice and nontransgenic littermates were given ethanol (20% v/v) and the anti-HIV drug 3,-azido-3,-deoxythymidine (AZT; 1 mg/ml) in drinking water. Immunosuppression in mice was induced by weekly intraperitoneal injections of anti-CD4 antibody. Hematopoiesis was examined by erythroid colony forming unit (CFU-E) and granulocyte/macrophage colony-forming unit (CFU-GM) assays of the bone marrow progenitor cells. Results: Administration of ethanol for 7 weeks resulted in a 50% decrease in the proliferative capacity of CFU-E- and CFU-GM-derived progenitors from transgenic mice compared with that of ethanol-treated nontransgenic controls. Similar decreases also were observed in transgenic mice treated with AZT or a combination of AZT and ethanol. Furthermore, ethanol and AZT were significantly more toxic to the granulopoietic progenitors (40,50% inhibition) than to the erythropoietic progenitors (10,20% inhibition) in Tat transgenic mice. Although a 10 day exposure of Tat transgenic and nontransgenic mice to a combination of ethanol and AZT had no suppressive effect on the erythropoietic and granulopoietic progenitor cells, there was a marked decrease (40,60%) in CFU-GM in mice made immunodeficient by CD4+ T-lymphocyte depletion. The ethanol-treated Tat transgenic mice but not the nontransgenic littermates also showed a significant decrease (25%) in CFU-GM. Conclusion: Our in vivo study strongly suggests that ethanol ingestion in HIV-1-infected individuals, particularly those on antiretroviral drugs, might increase bone marrow toxicity and contribute to HIV-1-associated hematopoietic impairment. [source] Incontinentia Pigmenti in Boys: A Series and Review of the LiteraturePEDIATRIC DERMATOLOGY, Issue 6 2006Daniela Ardelean M.D. Occurrences of this disease in boys have been reported, however, its clinical phenotype has not been well characterized. The purpose of this study was to report on additional instances of incontinentia pigmenti in boys and to review the clinical, laboratory, and molecular characteristics of all published such patients. A retrospective chart review and Medline search using the keywords incontinentia pigmenti, males, and NEMO gene was undertaken. Six new boys with incontinentia pigmenti were found in our database and 36 more were previously reported in the literature. The vesiculo-bullous stage was the most frequent clinical presentation at diagnosis (80%). Fifteen percent of patients had an initial unilateral presentation. Recurrences of this stage were noted in 16%. Stages 2 and 3 of the disease were present in only 72.5% and 75% of patients, respectively. Only 15% of the boys had a documented stage 4. Extracutaneous manifestations were also documented (30%, central nervous system manifestations, 35%, eye involvement, 30%, alopecia, 40%, teeth anomalies). Thirty two percent of boys had peripheral eosinophilia. Only five had evidence of NEMO gene mutation. The male phenotype has clinical features similar to those of the female phenotype. Unilateral presentation is a distinct occurrence in boys, especially in early stages. Anomalies are the most common extracutaneous findings, followed by eye, hair, and central nervous system abnormalities. [source] Septo-optic dysplasia as a manifestation of valproic acid embryopathyBIRTH DEFECTS RESEARCH, Issue 2 2001Carrie L. McMahon Background The use of valproic acid during pregnancy has been associated with adverse fetal outcomes, including major and minor congenital malformations, intrauterine growth retardation (IUGR), hyperbilirubinemia, hepatotoxicity, transient hyperglycemia, and fetal and neonatal distress. In addition, intrauterine exposure to valproic acid has been associated with an increased risk of central nervous system abnormalities, primarily neural tube defects. Optic nerve hypoplasia has been reported in association with other prenatal anticonvulsant exposures, but the occurrence of septo-optic dysplasia as a manifestation of valproic acid embryopathy has not been reported previously. Results We report on a woman who received Depakote (valproic acid) throughout her pregnancy for the treatment of a seizure disorder. The patient presented with features typical of valproic acid embryopathy, including bitemporal narrowing, hypertelorism, short palpebral fissures, epicanthal folds, microphthalmia, a flat broad nasal bridge, small mouth, hypoplastic nails, mild clinodactyly, and camptodactyly. MRI showed hypoplasia of the optic chiasm and absence of the septum pellucidum. Conclusions We report the first case of septo-optic dysplasia associated with maternal exposure to valproic acid throughout pregnancy. This case expands the clinical phenotype of valproate embryopathy. Teratology 64:83,86, 2001. © 2001 Wiley-Liss, Inc. [source] A ventral prefrontal-amygdala neural system in bipolar disorder: a view from neuroimaging researchACTA NEUROPSYCHIATRICA, Issue 5 2009Fay Y. Womer In the past decade, neuroimaging research has identified key components in the neural system that underlies bipolar disorder (BD). The ventral prefrontal cortex (VPFC) and amygdala are highly interconnected structures that jointly play a central role in emotional regulation. Numerous research groups have reported prominent structural and functional abnormalities within the VPFC and amygdala supporting their essential role in a neural system underlying the emotional dysregulation that is a core feature of BD. Findings in BD also include those in brain regions interconnected with the VPFC and amygdala, including the ventral striatum, hippocampus and the cerebellum. Abnormalities in these regions may contribute to symptoms that reflect disruption in functions sub-served by these structures, including motivational, mnemonic and psychomotor functions. This article will first review leads from behavioural neurology that implicated these neural system abnormalities in BD. It will then review findings from structural and functional imaging studies to support the presence of abnormalities within these neural system components in BD. It will also review new findings from studies using diffusion tensor imaging (DTI) that provide increasing evidence of abnormalities in the connections between these neural system components in BD. Emerging data supporting differences in this neural system during adolescence, as well as potential beneficial effects of treatment on structure and function will also be presented. Finally, the article will discuss the implications for future investigations, including those for early identification and treatment of BD. [source] Cornelia de Lange syndrome, cohesin, and beyondCLINICAL GENETICS, Issue 4 2009J Liu Cornelia de Lange syndrome (CdLS) (OMIM #122470, #300590 and #610759) is a dominant genetic disorder with multiple organ system abnormalities which is classically characterized by typical facial features, growth and mental retardation, upper limb defects, hirsutism, gastrointestinal and other visceral system involvement. Mutations in three cohesin proteins, a key regulator of cohesin, NIPBL, and two structural components of the cohesin ring SMC1A and SMC3, etiologically account for about 65% of individuals with CdLS. Cohesin controls faithful chromosome segregation during the mitotic and meiotic cell cycles. Multiple proteins in the cohesin pathway are also involved in additional fundamental biological events such as double-strand DNA break repair and long-range regulation of transcription. Moreover, chromosome instability was recently associated with defective sister chromatid cohesion in several cancer studies, and an increasing number of human developmental disorders is being reported to result from disruption of this pathway. Here, we will discuss the human disorders caused by alterations of cohesin function (termed ,cohesinopathies'), with an emphasis on the clinical manifestations of CdLS and mechanistic studies of the CdLS-related proteins. [source] Recombinant chromosome 10 presenting as a prenatal central nervous system abnormalityPRENATAL DIAGNOSIS, Issue 10 2009April T. Tritto No abstract is available for this article. [source] | |||||||||||||