81 research outputs found

    Segregation distortion of wild-type alleles at the Machado-Joseph disease locus: a study in normal families from the Azores islands (Portugal)

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    Machado-Joseph disease (MJD) is caused by an expansion of a triplet repeat with a CAG motif at the ATXN3 gene. The putative segregation ratio distortion (SRD) of alleles can play an important role in the non-Mendelian behaviour of triplet repeat loci. To study the stability and infer the segregation patterns of wild-type MJD alleles, the size of the (CAG)(n) tract was analysed in 102 normal sibships, representing 428 meioses. No mutational events were detected during the transmission of alleles. Segregation analysis showed that the smaller alleles were preferentially transmitted (56.9%). Considering maternal meioses alone, such preference was still detected (55.7%) but without statistical significance. A positive correlation was observed for the difference in length between the two alleles constituting the transmitters' genotype (D) and the frequency of transmission of the smaller alleles. The results suggest that small D values are not enough to modify the probability of allele transmission. When transmissions involving genotypes with D <or= 2 were excluded, SRD in favour of the smaller allele became significant for both maternal and paternal transmissions. Therefore, the genotypic composition of the transmitters in a sample to be analysed should influence the ability to detect SRD, acting as a confounding factor.This work was supported by ‘‘Projecto Regional Integrado— DMJ (PRI-DMJ)’’ (funded by Regional Government of the Azores), ‘‘Construyendo una Bio-Región Europea—Biopolis’’ (05/MAC/2.3/ C14, funded by PIC Interreg III B, Azores—Madeira—Canarias) and MANSEEBMO (MI.2.1/004/2005, funded by ‘‘Direcção Regional da Ciência e Tecnologia’’). CB (SFRH/BD/21875/2005) is a recipient of a Ph.D. grant, and RM (SFRH/BPD/32473/2006) and CS (SFRH/BPD/ 20944/2004) are postdoctoral fellows from ‘‘Fundação para a Ciência e a Tecnologia’’ (FCT)

    Swordfish bill injury involving abdomen and vertebral column: case report and review

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    <p>Abstract</p> <p>Background</p> <p>Penetrating injuries of the abdomen and spinal canal that involve organic material of animal origin are extremely rare and derive from domestic and wild animal attacks or fish attacks.</p> <p>Case presentation</p> <p>In this case report we present the unique, as far as the literature is concerned, unprovoked woman's injury to the abdomen by a swordfish. There are only four cases of swordfish attacks on humans in the literature - one resulted to thoracic trauma, two to head trauma and one to knee trauma, one of which was fatal - none of which were unprovoked. Three victims were professional or amateur fishermen whereas in the last reported case the victim was a bather as in our case. Our case is the only case where organic debris of animal's origin remained in the spinal canal after penetrating trauma.</p> <p>Conclusions</p> <p>Although much has been written about the management of penetrating abdominal and spinal cord trauma, controversy remains about the optimal management. Moreover, there is little experience in the management of patients with such spinal injuries, due to the fact that such cases are extremely rare. In this report we focus on the patient's treatment with regard to abdominal and spinal trauma and present a review of the literature.</p

    Dissociation between skin test reactivity and anti-aeroallergen IgE: Determinants among urban Brazilian children.

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    BACKGROUND: The dissociation between specific IgE and skin prick test reactivity to aeroallergens, a common finding in populations living in low and middle-income countries, has important implications for the diagnosis and treatment of allergic diseases. Few studies have investigated the determinants of this dissociation. In the present study, we explored potential factors explaining this dissociation in children living in an urban area of Northeast Brazil, focusing in particular on factors associated with poor hygiene. METHODS: Of 1445 children from low income communities, investigated for risk factors of allergies, we studied 481 with specific IgE antibodies to any of Blomia tropicalis, Dermatophagoides pteronyssinus, Periplaneta americana and Blatella germanica allergens. Data on demographic, environmental and social exposures were collected by questionnaire; serum IgG and stool examinations were done to detect current or past infections with viral, bacterial, protozoan and intestinal helminth pathogens. We measured atopy by skin prick testing (SPT) and specific IgE (sIgE) to aerollergens in serum (by ImmunoCAP). SIgE reactivity to B. tropicalis extract depleted of carbohydrates was measured by an in-house ELISA. Total IgE was measured by in house capture ELISA. SNPs were typed using Illumina Omni 2.5. RESULTS: Negative skin prick tests in the presence of specific IgE antibodies were frequent. Factors independently associated with a reduced frequency of positive skin prick tests were large number of siblings, the presence of IgG to herpes simplex virus, Ascaris lumbricoides and Trichuris trichiura infections, living in neighborhoods with infrequent garbage collection, presence of rodents and cats in the household and sIgE reactivity to glycosylated B. tropicalis allergens. Also, SNP on IGHE (rs61737468) was negatively associated with SPT reactivity. CONCLUSIONS: A variety of factors were found to be associated with decreased frequency of SPT such as unhygienic living conditions, infections, total IgE, IgE response to glycosylated allergens and genetic polymorphisms, indicating that multiple mechanisms may be involved. Our data, showing that exposures to an unhygienic environment and childhood infections modulate immediate allergen skin test reactivity, provide support for the "hygiene hypothesis"

    Immunoregulation in human malaria: the challenge of understanding asymptomatic infection

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    Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

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    Adenosine is a neuromodulator that operates via the most abundant inhibitory adenosine A1 receptors (A1Rs) and the less abundant, but widespread, facilitatory A2ARs. It is commonly assumed that A1Rs play a key role in neuroprotection since they decrease glutamate release and hyperpolarize neurons. In fact, A1R activation at the onset of neuronal injury attenuates brain damage, whereas its blockade exacerbates damage in adult animals. However, there is a down-regulation of central A1Rs in chronic noxious situations. In contrast, A2ARs are up-regulated in noxious brain conditions and their blockade confers robust brain neuroprotection in adult animals. The brain neuroprotective effect of A2AR antagonists is maintained in chronic noxious brain conditions without observable peripheral effects, thus justifying the interest of A2AR antagonists as novel protective agents in neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, ischemic brain damage and epilepsy. The greater interest of A2AR blockade compared to A1R activation does not mean that A1R activation is irrelevant for a neuroprotective strategy. In fact, it is proposed that coupling A2AR antagonists with strategies aimed at bursting the levels of extracellular adenosine (by inhibiting adenosine kinase) to activate A1Rs might constitute the more robust brain neuroprotective strategy based on the adenosine neuromodulatory system. This strategy should be useful in adult animals and especially in the elderly (where brain pathologies are prevalent) but is not valid for fetus or newborns where the impact of adenosine receptors on brain damage is different
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