LHRH-A对孕中期大鼠抗妊娠作用的研究

本文观察了[D-Ala⁶,Pro⁹-Ethylamide¹⁰]-LHRH(LHRH-A)对孕中期大鼠的抗妊娠作用。结果显示:在孕9～11d sc 200μg/d LHRH-A,血浆孕酮水平自第二次给药后明显下降(P<0.05),给药大鼠均流产终止妊娠;LHRH-A的抗妊娠作用可被醋酸甲地孕酮所拮抗;LHRH-A对体外培养的假孕大鼠和孕d 9大鼠黄体细胞分泌孕酮有明显的直接抑制作用。     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

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.     

Past exposure and the dynamics of lymphatic filariasis infection in young children.

This study utilizes parallel, longitudinal entomological and parasitological data collected during a 5-year vector control programme in Pondicherry, South India, to quantify Wuchereria bancrofti transmission from the vector to the human population. A simple mathematical model, derived from the standard catalytic model, is used to examine the hypothesis that current infection prevalence in young children is a dynamical function of their cumulative past exposure to infective bites. Maximum likelihood fits of the model to the observed data indicate a constant child infection rate with age, above a threshold representing the pre-patent period, or equivalently, the cumulative biting intensity required to produce patent infections. Extrapolation of the model allows the crude estimation of the equilibrium microfilaria age-prevalence curve due to control. The results suggest that vector control alone may have little impact on the overall age-prevalence of infection even when sustained for long periods. These observations are discussed in terms of the likely impact of density dependent mechanisms, such as acquired immunity, on model predictions.     

Evaluation and audit in a paediatric disability service

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.     

Temporal accrual of complement proteins in amyloid plaques in Down's syndrome with Alzheimer's disease

The complement system constitutes a series of enzymatic steps involved in the inflammatory response and is activated in Alzheimer's disease (AD). Using Down's syndrome (DS) brains as a temporal model for the progression of AD, we examined components of the complement cascade and their relationship to other principal events in AD pathology: Abeta42 deposition, neuritic changes, neurofibrillary tangles (NFTs), and gliosis (reactive astrocytes, activated microglia). Adjacent sections of frontal cortex from 24 DS subjects ranging in age from 12 to 73 years were immunohistochemically examined for immunoreactivity (IR) of classical complement proteins (Clq and C3), markers indicating activation of complement (C4d and C5b-9), the complement inhibitor apolipoprotein J (apo J), and markers of AD neuropathology. Abeta42-labeled diffuse plaques were first detected in a 12-year-old DS subject and were not labeled by any of the complement antibodies. Colocalization of Abeta42 with Clq, C3, C4d, and/or apo J was first detected in compacted plaques in the brain of a 15-year-old DS patient with features of mature AD pathology, such as reactive astrocytes, activated microglia, dystrophic neurites, and a few NFTs. IR for C4d and C5b-9 (membrane attack complex, MAC) was observed in small numbers of plaque-associated dystrophic neurites and in focal regions of pyramidal neurons in this 15-year-old. The only other young (相似文献   

The AMY Antigen Co-Occurs with Aβ and Follows Its Deposition in the Amyloid Plaques of Alzheimer’s Disease and Down Syndrome

Novel plaque-like "AMY" lesions were recently described in the brains of patients with Alzheimer's disease (AD). Using three Abeta antibodies, we now document the co-occurrence of AMY immunoreactivity (IR) with amyloid beta-peptide (Abeta) in the large majority of plaques in AD brain. AMY IR was detected in many compacted plaques, whereas its co-localization with early, diffuse Abeta deposits was rare. AMY IR overlapped considerably or fully with Abeta and, in more severely affected AD brains, decorated the periphery of some plaques. In a temporal series of 29 Down syndrome (DS) brains from patients aged 12 to 73 years, the earliest AMY IR was detected in some plaques at age 15, following the earliest appearance of Abeta plaques (age 12 years), and then accrued within a subset of Abeta deposits, namely, the more spherical, compacted plaques. Brains from DS patients 29 years and older showed AMY staining in many Abeta plaques, as seen in AD. Brains from eight monkeys aged 17 to 34 years and thirty APP transgenic mice aged 8 to 20 months showed Abeta IR but no AMY IR. We conclude that AMY IR represents an amyloid-associated antigen that co-deposits in most but not all Abeta plaques in AD and DS and that accumulation of the AMY antigen follows Abeta deposition in plaques.     

Acute renal failure in diabetics

Conclusions Acute renal failure in diabetic patients occurs, as a result of certain specific conditions. The most common of these are hyperglycaemic hyperosmolar coma, diabetic ketoacidosis, the use of radiocontrast media, and renal papillary necrosis. The management of diabetics with acute renal failure is essentially the same as for non-diabetic patients but may be complicated by the problems of metabolic control, vascular access, and vascular instability. Prevention is important as the development of acute renal failure adds considerably to the morbidity and mortality of these conditions and is often avoidable.Wellcome Research Fellow     

Fertility and digital technology: narratives of using smartphone app ‘Natural Cycles’ while trying to conceive

Fertility awareness apps, which help to identify the ‘fertile window’ when conception is most likely, have been hailed as ‘revolutionising’ women’s reproductive health. Despite rapidly growing popularity, little research has explored how people use these apps when trying to conceive and what these apps mean to them. We draw on in‐depth, qualitative interviews, adopting a critical digital health studies lens (a sub‐field of science and technology studies), to explore the experiences of cisgender women and partners with one such app, Natural Cycles, in the context of their daily lives. We found that many women valued the technology as a ‘natural’, inobtrusive alternative to biomedical intervention, and a means of controlling and knowing their bodies, amid a dearth of fertility‐related education and care. Yet this technology also intervened materially and affectively into the spaces of their lives and relationships and privileged disembodied metrics (temperature) over embodied knowledge. Meanwhile, app language, advertising and cost have contributed to characterising ‘typical’ users as white, heterosexual, affluent, cisgender women without disabilities. In the context of neoliberal shifts towards bodily self‐tracking, technologies appealing as novel, liberating and ‘natural’ to individuals who can access them may nevertheless reproduce highly gendered reproductive responsibilities, anxieties and broader health and social inequalities.     

总粉尘浓度转换为呼吸性粉尘浓度的两种方法学研究

目的探讨流行病学研究中历史性总粉尘浓度转换成呼吸性粉尘浓度的理论方法。方法采用两种方法：一种通过体积直接计算;另一种用ＨａｔｃｈＣｈｏａｔｅ方程计算,推导出计数百分比和计量百分比的转换关系。结果得到总粉尘浓度与呼吸性粉尘浓度的理论转换系数,其中,用ＨａｔｃｈＣｈｏａｔｅ方程计算结果偏低。结论体积直接计算法更适用。