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Zuzana Kasanova Dennis Hernaus Thomas Vaessen Thérèse van Amelsvoort Oliver Winz Alexander Heinzel Jens Pruessner Felix M. Mottaghy Dina Collip Inez Myin-Germeys 《PloS one》2016,11(3)
Early life stress may have a lasting impact on the developmental programming of the dopamine (DA) system implicated in psychosis. Early adversity could promote resilience by calibrating the prefrontal stress-regulatory dopaminergic neurotransmission to improve the individual’s fit with the predicted stressful environment. Aberrant reactivity to such match between proximal and distal environments may, however, enhance psychosis disease risk. We explored the combined effects of childhood adversity and adult stress by exposing 12 unmedicated individuals with a diagnosis of non-affective psychotic disorder (NAPD) and 12 healthy controls (HC) to psychosocial stress during an [18F]fallypride positron emission tomography. Childhood trauma divided into early (ages 0–11 years) and late (12–18 years) was assessed retrospectively using a questionnaire. A significant group x childhood trauma interaction on the spatial extent of stress-related [18F]fallypride displacement was observed in the mPFC for early (b = -8.45, t(1,23) = -3.35, p = .004) and late childhood trauma (b = -7.86, t(1,23) = -2.48, p = .023). In healthy individuals, the spatial extent of mPFC DA activity under acute psychosocial stress was positively associated with the severity of early (b = 7.23, t(11) = 3.06, p = .016) as well as late childhood trauma (b = -7.86, t(1,23) = -2.48, p = .023). Additionally, a trend-level main effect of early childhood trauma on subjective stress response emerged within this group (b = -.7, t(11) = -2, p = .07), where higher early trauma correlated with lower subjective stress response to the task. In the NAPD group, childhood trauma was not associated with the spatial extent of the tracer displacement in mPFC (b = -1.22, t(11) = -0.67), nor was there a main effect of trauma on the subjective perception of stress within this group (b = .004, t(11) = .01, p = .99). These findings reveal a potential mechanism of neuroadaptation of prefrontal DA transmission to early life stress and suggest its role in resilience and vulnerability to psychosis. 相似文献
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Irisin was first identified in muscle cells. We detected irisin immunoreactivity in various organs of the crested porcupine (Hystrix cristata). In the epidermis, irisin immunoreactivity was localized mainly in stratum basale, stratum spinosum and stratum granulosum layers; immunoreactivity was not observed in the stratum corneum. In the dermis, irisin was found in the external and internal root sheath, cortex and medulla of hair follicles, and in sebaceous glands. Irisin immunoreactivity was found in the neural retina and skeletal muscle fibers associated with the eye. The pineal and thyroid glands also exhibited irisin immunoreactivity. 相似文献
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Andréia S Lessa Bruno D Paredes Juliana V Dias Adriana B Carvalho Luiz Fernando Quintanilha Christina M Takiya Bernardo R Tura Guilherme FM Rezende Antonio C Campos de Carvalho Célia MC Resende Regina CS Goldenberg 《BMC veterinary research》2010,6(1):1-10
Background
Atypical scrapie was first identified in Norwegian sheep in 1998 and has subsequently been identified in many countries. Retrospective studies have identified cases predating the initial identification of this form of scrapie, and epidemiological studies have indicated that it does not conform to the behaviour of an infectious disease, giving rise to the hypothesis that it represents spontaneous disease. However, atypical scrapie isolates have been shown to be infectious experimentally, through intracerebral inoculation in transgenic mice and sheep. The first successful challenge of a sheep with 'field' atypical scrapie from an homologous donor sheep was reported in 2007.Results
This study demonstrates that atypical scrapie has distinct clinical, pathological and biochemical characteristics which are maintained on transmission and sub-passage, and which are distinct from other strains of transmissible spongiform encephalopathies in the same host genotype.Conclusions
Atypical scrapie is consistently transmissible within AHQ homozygous sheep, and the disease phenotype is preserved on sub-passage. 相似文献5.
Elisabeth APM Romme Piet Geusens Willem F Lems Erica PA Rutten Frank WJM Smeenk Joop PW van den Bergh Peter ThW van Hal Emiel FM Wouters 《Respiratory research》2015,16(1)
Although osteoporosis and its related fractures are common in patients with COPD, patients at high risk of fracture are poorly identified, and consequently, undertreated. Since there are no fracture prevention guidelines available that focus on COPD patients, we developed a clinical approach to improve the identification and treatment of COPD patients at high risk of fracture. We organised a round-table discussion with 8 clinical experts in the field of COPD and fracture prevention in the Netherlands in December 2013. The clinical experts presented a review of the literature on COPD, osteoporosis and fracture prevention. Based on the Dutch fracture prevention guideline, they developed a 5-step clinical approach for fracture prevention in COPD. Thereby, they took into account both classical risk factors for fracture (low body mass index, older age, personal and family history of fracture, immobility, smoking, alcohol intake, use of glucocorticoids and increased fall risk) and COPD-specific risk factors for fracture (severe airflow obstruction, pulmonary exacerbations and oxygen therapy). Severe COPD (defined as postbronchodilator FEV1 < 50% predicted) was added as COPD-specific risk factor to the list of classical risk factors for fracture. The 5-step clinical approach starts with case finding using clinical risk factors, followed by risk evaluation (dual energy X-ray absorptiometry and imaging of the spine), differential diagnosis, treatment and follow-up. This systematic clinical approach, which is evidence-based and easy-to-use in daily practice by pulmonologists, should contribute to optimise fracture prevention in COPD patients at high risk of fracture. 相似文献
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Erika H Noss Gerald FM Watts Davide Zocco Tracy L Keller Malcolm Whitman Carl P Blobel David M Lee Michael B Brenner 《Arthritis research & therapy》2015,17(1)
IntroductionEngagement of the homotypic cell-to-cell adhesion molecule cadherin-11 on rheumatoid arthritis (RA) synovial fibroblasts with a chimeric molecule containing the cadherin-11 extracellular binding domain stimulated cytokine, chemokine, and matrix metalloproteinases (MMP) release, implicating cadherin-11 signaling in RA pathogenesis. The objective of this study was to determine if cadherin-11 extracellular domain fragments are found inside the joint and if a physiologic synovial fibroblast cleavage pathway releases those fragments.MethodsCadherin-11 cleavage fragments were detected by western blot in cell media or lysates. Cleavage was interrupted using chemical inhibitors or short-interfering RNA (siRNA) gene silencing. The amount of cadherin-11 fragments in synovial fluid was measured by western blot and ELISA.ResultsSoluble cadherin-11 extracellular fragments were detected in human synovial fluid at significantly higher levels in RA samples compared to osteoarthritis (OA) samples. A cadherin-11 N-terminal extracellular binding domain fragment was shed from synovial fibroblasts after ionomycin stimulation, followed by presenilin 1 (PSN1)-dependent regulated intramembrane proteolysis of the retained membrane-bound C-terminal fragments. In addition to ionomycin-induced calcium flux, tumor necrosis factor (TNF)-α also stimulated cleavage in both two- and three-dimensional fibroblast cultures. Although cadherin-11 extracellular domains were shed by a disintegrin and metalloproteinase (ADAM) 10 in several cell types, a novel ADAM- and metalloproteinase-independent activity mediated shedding in primary human fibroblasts.ConclusionsCadherin-11 undergoes ectodomain shedding followed by regulated intramembrane proteolysis in synovial fibroblasts, triggered by a novel sheddase that generates extracelluar cadherin-11 fragments. Cadherin-11 fragments were enriched in RA synovial fluid, suggesting they may be a marker of synovial burden and may function to modify cadherin-11 interactions between synovial fibroblasts.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0647-9) contains supplementary material, which is available to authorized users. 相似文献7.
Advanced personalized dosimetry for molecular nuclear therapy has been shown to be feasible in clinical practice. At the same time instrumentation and dosimetric software are still evolving at a high pace. Procedures developed so far differ in approach and sophistication, and standard operating procedures necessary for accurate patient specific dosimetry do not yet exist. For this reason we restricted ourselves to reviewing the literature and highlighting relevant developments. 相似文献
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Amukotuwa S Choong PF Smith PJ Powell GJ Slavin J Schlicht SM 《International Seminars in Surgical Oncology : ISSO》2005,2(1):10
BACKGROUND: Extrapulmonary tuberculosis is one of the great mimickers of medicine, and often masquerades as malignancy. As a result, patients may be referred to oncologists and surgeons for further evaluation and management, delaying the institution of appropriate anti-tuberculous drug therapy. CASE PRESENTATION: We present the case of a 21 year old man with tuberculous osteomyelitis, who was referred to the Bone and Soft Tissue Sarcoma Service at our institution with a provisional diagnosis of malignancy. Further investigation revealed extensive retroperitoneal abdominal and pelvic lymphadenopathy. The recognition of certain patterns on imaging, and finally the isolation of Mycobacterium tuberculosis from tissue samples obtained under image guidance, enabled the correct diagnosis to be made. CONCLUSION: This case highlights the importance of remaining cognisant of the protean manifestations of extrapulmonary tuberculosis, and illustrates the advantage of a clinically directed multi-modality imaging approach to diagnosis. 相似文献
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Marijke De Saint-Hubert Felix M. Mottaghy Kathleen Vunckx Johan Nuyts Humphrey Fonge Kristof Prinsen Sigrid Stroobants Luc Mortelmans Niko Deckers Leo Hofstra Chris P.M. Reutelingsperger Alfons Verbruggen Dirk Rattat 《Bioorganic & medicinal chemistry》2010,18(3):1356-1363
In this study ‘second generation’ AnxV was specifically labeled with 99mTc in three different ways outside the binding region of the protein to obtain an improved target-to-background activity ratio. The compounds were tested in vitro and in vivo in normal mice and in a model of hepatic apoptosis (anti-Fas mAb). The apoptosis binding was most prominent for the HIS-tagged ‘second generation’ AnxV labeled with 99mTc(CO)3 in comparison to 99mTc-HYNIC-cys-AnxV and 99mTc(CO)3-DTPA-cys-AnxV. 相似文献
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Judith Zhi-Yie Tan Stephen M Schlicht Gerard J Powell David Thomas John L Slavin Peter J Smith Peter FM Choong 《International Seminars in Surgical Oncology : ISSO》2006,3(1):38