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Inclusion Disease (inclusion + disease)
Selected AbstractsFragile X-associated Tremor/Ataxia Syndrome (FXTAS)DEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 1 2004Paul J. Hagerman Abstract Carriers of fragile X mental retardation 1 (FMR1) premutation alleles (55 to 200 CGG repeats) are generally spared the more serious neurodevelopmental problems associated with the full-mutation carriers (>200 repeats) of fragile X syndrome. However, some adult male premutation carriers (55,200 repeats) develop a neurological syndrome involving intention tremor, ataxia, dementia, parkinsonism, and autonomic dysfunction. In excess of one-third of male premutation carriers over 50 years of age develop the fragile X- associated tremor/ataxia syndrome (FXTAS). FXTAS also represents a new form of inclusion disease, with eosinophilic intranuclear inclusions found throughout the brain in both neurons and astrocytes. Because FXTAS appears to be relatively specific to male premutation carriers, who are known to possess elevated levels of FMR1 mRNA, the neuropathology may arise as a consequence of a toxic gain-of-function of the mRNA itself, although this proposal requires additional direct testing. One of the critical needs at present is a better estimate for the prevalence of this disorder, because FXTAS is likely to be underdiagnosed in the adult movement disorders clinics. MRDD Research Reviews 2004;10:25,30. © 2004 Wiley-Liss, Inc. [source] Does cytomegalovirus play a causative role in the development of various inflammatory diseases and cancer?JOURNAL OF INTERNAL MEDICINE, Issue 3 2006C. SÖDERBERG-NAUCLÉR Abstract. Human cytomegalovirus (HCMV) is a herpes virus that infects and is carried by 70,100% of the world's population. During its evolution, this virus has developed mechanisms that allow it to survive in an immunocompetent host. For many years, HCMV was not considered to be a major human pathogen, as it appeared to cause only rare cases of HCMV inclusion disease in neonates. However, HCMV is poorly adapted for survival in the immunosuppressed host and has emerged as an important human pathogen in AIDS patients and in patients undergoing immunosuppressive therapy following organ or bone marrow transplantation. HCMV-mediated disease in such patients has highlighted the possible role of this virus in the development of other diseases, in particular inflammatory diseases such as vascular diseases, autoimmune diseases and, more recently, with certain forms of cancers. Current research is focused on determining whether HCMV plays a causative role in these diseases or is merely an epiphenomenon of inflammation. Inflammation plays a central role in the pathogenesis of HCMV. This virus has developed a number of mechanisms that enable it to hide from the cells of the immune system and, at the same time, reactivation of a latent infection requires immune activation. Numerous products of the HCMV genome are devoted to control central functions of the innate and adaptive immune responses. By influencing the regulation of various cellular processes including the cell cycle, apoptosis and migration as well as tumour invasiveness and angiogenesis, HCMV may participate in disease development. Thus, the various drugs now available for treatment of HCMV disease (e.g. ganciclovir, acyclovir and foscarnet), may also prove to be useful in the treatment of other, more widespread diseases. [source] The prognostic value of ultrasound abnormalities and biological parameters in blood of fetuses infected with cytomegalovirusBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 7 2008G Benoist Objective, To evaluate the prognostic value of ultrasound abnormalities and of selected biological parameters in blood of fetuses infected with cytomegalovirus (CMV). Design, Retrospective observational study. Setting, Two fetal medicine units in Paris, France. Population, All fetuses infected with CMV referred between 1998 and 2006. Methods, We retrospectively analysed data collected prospectively in 73 fetuses infected by CMV with a positive CMV polymerase chain reaction in amniotic fluid. Fetal blood sampling (FBS) was performed for evaluation of platelet count, plasma levels of aminotransferases and gamma-glutamyl transpeptidases (GGT), presence of viraemia and specific fetal immunoglobulin M. Targeted ultrasound examination was performed every fortnight. Ultrasound findings were categorised into normal examination and any ultrasound abnormality, which was further grouped as ultrasound abnormality of the fetal brain and noncerebral ultrasound abnormality. Main outcome measures, A combination of histological findings after termination of pregnancy and evidence of cytomegalic inclusion disease at birth when pregnancies were continued. Clinical symptoms at birth or histological lesions attributable to CMV were considered as poor outcome. Statistical analysis was conducted to determine the value of each parameter to predict outcome. Logistic regression was used to build up a multivariate model combining the relevant parameters. Results, In univariate analysis, only thrombocytopenia and the presence of any ultrasound abnormality were associated with a poor outcome (P < 10,4 for both abnormalities). In the multivariate analysis, both thrombocytopenia and the presence of ultrasound abnormalities remained significant independent predictors of a poor outcome. Based on univariate logistic regression, odds ratio for a poor outcome were 1.24, 7.2, 22.5 and 25.5 for each 10 000/mm3 decrease in platelet count, the presence of noncerebral, any ultrasound and cerebral ultrasound abnormalities, respectively. Conclusions, The prognosis of CMV-infected fetuses relies independently on both targeted ultrasound examination and fetal platelet count. FBS for platelet count may therefore justify FBS in infected fetuses even in the absence of ultrasound. features of brain involvement. [source] FUS-Immunoreactive Intranuclear Inclusions in Neurodegenerative DiseaseBRAIN PATHOLOGY, Issue 3 2010John Woulfe Abstract Neuronal intranuclear inclusions (NIIs) are a histopathological hallmark of several neurodegenerative disorders. However, the role played by NIIs in neurodegenerative pathogenesis remains enigmatic. Defining their molecular composition represents an important step in understanding the pathophysiology of these disorders. Recently, a nuclear protein, "fused-in-sarcoma" (FUS) was identified as the pathological protein in two forms of frontotemporal lobar degeneration (FTLD-IF, formerly known as neuronal intermediate filament inclusion disease, and FTLD-UPS, formerly known as atypical FTLD-U), both of which are characterized by the presence of NII. The objective of the present study was to determine the range of neurodegenerative disorders characterized by FUS-positive NIIs. Immunostaining for FUS revealed intense reactivity of NIIs in FTLD-IF and FTLD-UPS as well as in Huntington's disease, spinocerebellar ataxias 1 and 3, and neuronal intranuclear inclusion body disease. In contrast, there was no FUS staining of NIIs in inherited forms of FTLD-TDP caused by GRN and VCP mutations, fragile-X-associated tremor ataxia syndrome, or oculopharyngeal muscular dystrophy. In a cell culture model of Huntington's disease, NIIs were intensely FUS-positive. NII-bearing cells displayed loss of the normal diffuse nuclear pattern of FUS staining. This suggests that sequestration of nuclear FUS by NIIs may interfere with its normal nuclear localization. [source] | ||||||||||