The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD. 相似文献
Parental and professional responses to questionnaires evaluating a paediatric disability service are reported and the viability of auditing structural, process, and outcome aspects of clinical practice are discussed. Expectations of waiting time to first appointment (met for only 52% of consumers) illustrate structural issues. Process issues are reflected in consumer reactions to outreach work (for example, 94% of parents and 84% of professionals found this supportive). Outcome measures such as consumer satisfaction with the service (76% of consumers reported being 'very satisfied' and 20% 'fairly satisfied') suggest that service aims are being met. Good concurrence of service aims with consumer needs is indicated by parental reasons for referral (for example, 75% for diagnostic help, 73% for a better understanding of the disorder, 88% for practical help), referrers' reasons (for example, 55% for a second diagnostic opinion, 45% due to lack of local expertise), and reports from most other professionals involved with the case that a similar service was not provided locally. 相似文献
AIMS: To study the effect of prone and supine sleep on infant behaviour, peripheral skin temperature, and cardiorespiratory parameters to aid understanding of why prone sleeping is associated with an increased risk of sudden infant death syndrome. METHODS: Of 33 enrolled infants, 32 were studied at 2.5 and 28 at 5 months of age. A computer aided multichannel system was used for polysomnographic recordings. Behaviour was charted separately. RESULTS: Prone REM (active) sleep was associated with lower frequencies of short arousals, body movements and sighs, and a shorter duration of apnoeas than supine REM sleep at both ages. At 2.5 months there were less frequent episodes of periodic breathing during prone sleep in non-REM (quiet) and REM sleep. Heart rate and peripheral skin temperature were higher in the prone position during both sleep states at both ages. CONCLUSIONS: The observation of decreased variation in behaviour and respiratory pattern, increased heart rate, and increased peripheral skin temperature during prone compared with supine sleep may indicate that young infants are less able to maintain adequate respiratory and metabolic homoeostasis during prone sleep. 相似文献
Purpose: To review literature specific to the use of AAC with adults who have severe aphasia. Method: The authors reviewed studies involving AAC interventions for adults with severe aphasia. Results: Published data support the use of aided and unaided AAC with adults with severe aphasia in controlled treatment contexts. Reported gains in communication typically have not generalized to everyday settings. Conclusions: The application of AAC with persons with severe aphasia must address factors potentially limiting treatment success outside of training environments. 相似文献
Background: Pentraxin 3 (PTX3) is an acute phase reactant which has been used to detect intra-amniotic infections (IAI) in pregnancy, but the prognostic value of PTX3 concentrations on neonates has not been studied. We aimed to investigate the relationship between maternal PTX3–neonatal PTX3 concentrations and early neonatal outcome.
Methods: The mothers diagnosed with preterm prelabor rupture of membranes (PPROM) (n?=?28) and their preterm infants (n?=?28) were included in the study. PTX3 concentrations were studied in plasma in the maternal peripheral blood and umbilical/peripheral vein in the neonates. The relationship between the mPTX3–nPTX3 concentrations and neonatal outcome were investigated using non-parametric tests and binary logistic regression analysis.
Results: The mean mPTX3 concentration was 10.35?±?7.82?μg/L. Ten (35.7%) of all mothers were within the normal range and 18 (64.3%) in high percentile (≥97.5 percentile). There was no relation between mPTX3 concentrations and clinical or histologic chorioamnionitis, latency of PPROM, and early neonatal outcome. Mean nPTX3 concentrations was 9.18?±?7.83?μg/L and high nPTX3 concentrations were detected in five (17.8%) neonates. nPTX3 concentrations were inversely correlated with gestational age and correlated with rate of intraventricular hemorrhage (IVH) and mortality. Neonates with high nPTX3 concentrations also have lowered APGAR scores, increased rate of respiratory distress syndrome, clinical sepsis, IVH, necrotizing enterocolitis and prolonged NICU stay.
Conclusion: High PTX3 concentrations of the newborns are associated with some worsened early neonatal outcome including lower gestational age at delivery, increased rate of IVH and mortality. Maternal PTX3 concentrations are not an adequate marker in defining clinical or histologic chorioamnionitis and early neonatal outcome. 相似文献