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Christopher D Hue Frances S Cho Siqi Cao Cameron R ”Dale” Bass David F Meaney Barclay Morrison III 《Journal of cerebral blood flow and metabolism》2015,35(7):1191-1198
Owing to the frequent incidence of blast-induced traumatic brain injury (bTBI) in recent military conflicts, there is an urgent need to develop effective therapies for bTBI-related pathologies. Blood-brain barrier (BBB) breakdown has been reported to occur after primary blast exposure, making restoration of BBB function and integrity a promising therapeutic target. We tested the hypothesis that treatment with dexamethasone (DEX) after primary blast injury potentiates recovery of an in vitro BBB model consisting of mouse brain endothelial cells (bEnd.3). DEX treatment resulted in complete recovery of transendothelial electrical resistance and hydraulic conductivity 1 day after injury, compared with 3 days for vehicle-treated injured cultures. Administration of RU486 (mifepristone) inhibited effects of DEX, confirming that barrier restoration was mediated by glucocorticoid receptor signaling. Potentiated recovery with DEX treatment was accompanied by stronger zonula occludens (ZO)-1 tight junction immunostaining and expression, suggesting that increased ZO-1 expression was a structural correlate to BBB recovery after blast. Interestingly, augmented ZO-1 protein expression was associated with specific upregulation of the α+ isoform but not the α− isoform. This is the first study to provide a mechanistic basis for potentiated functional recovery of an in vitro BBB model because of glucocorticoid treatment after primary blast injury. 相似文献
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Rebecca L. King Albert C. Yan Debora R. Sekiguchi John K. Choi 《Journal of cutaneous pathology》2015,42(12):1012-1017
Reactive lymphoid infiltrates of the skin composed predominantly of gamma‐delta (γδ) T cells are not well described in the literature. Herein we report a case of an otherwise healthy 4‐year‐old male who presented with a waxing and waning papular rash characterized by small, discrete crusted papules spread across his trunk, face and extremities. Clinical evaluation revealed no evidence of systemic disease. Microscopic examination revealed a dermal, perivascular infiltrate of highly atypical lymphocytes with a γδ T cell phenotype, worrisome for primary cutaneous γδ T cell lymphoma. The clinical course, however, was that of a reactive condition and prompted consideration of a diagnosis of pityriasis lichenoides et varioliformis acuta (PLEVA) and lymphomatoid papulosis (LyP). In many ways, this case defies current classification schemes and seems to expand the spectrum of reactive γδ T cell infiltrates of the skin. 相似文献
5.
M. R. D. Maslin S. K. Lloyd S. Rutherford S. Freeman A. King D. R. Moore K. J. Munro 《Journal of the Association for Research in Otolaryngology》2015,16(5):631-640
Individuals with sudden unilateral deafness offer a unique opportunity to study plasticity of the binaural auditory system in adult humans. Stimulation of the intact ear results in increased activity in the auditory cortex. However, there are no reports of changes at sub-cortical levels in humans. Therefore, the aim of the present study was to investigate changes in sub-cortical activity immediately before and after the onset of surgically induced unilateral deafness in adult humans. Click-evoked auditory brainstem responses (ABRs) to stimulation of the healthy ear were recorded from ten adults during the course of translabyrinthine surgery for the removal of a unilateral acoustic neuroma. This surgical technique always results in abrupt deafferentation of the affected ear. The results revealed a rapid (within minutes) reduction in latency of wave V (mean pre = 6.55 ms; mean post = 6.15 ms; p < 0.001). A latency reduction was also observed for wave III (mean pre = 4.40 ms; mean post = 4.13 ms; p < 0.001). These reductions in response latency are consistent with functional changes including disinhibition or/and more rapid intra-cellular signalling affecting binaurally sensitive neurons in the central auditory system. The results are highly relevant for improved understanding of putative physiological mechanisms underlying perceptual disorders such as tinnitus and hyperacusis. 相似文献
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Understanding the contribution of endothelial cells to the progenitor pools of adult tissues has the potential to inform therapies for human disease.To address whether endothelial cells transdifferentiate into non-vascular cell types,we performed cell lineage tracing analysis using transgenic mice engineered to express a fluorescent marker following activation by tamoxifen in vascular endothelial cadherin promoter-expressing cells(VEcad-CreERT2;B6 Cg-Gt(ROSA)26Sortm9(CAG-tdTomato)Hze).Activation of target-cell labeling following 1.5 months of ad libitum feeding with tamoxifen-laden chow in 4–5 month-old mice resulted in the tracing of central nervous system and peripheral cells that include:cerebellar granule neurons,ependymal cells,skeletal myocytes,pancreatic beta cells,pancreatic acinar cells,tubular cells in the renal cortex,duodenal crypt cells,ileal crypt cells,and hair follicle stem cells.As Nestin expression has been reported in a subset of endothelial cells,Nes-CreERT2 mice were also utilized in these conditions.The tracing of cells in adult Nes-CreERT2 mice revealed the labeling of canonical progeny cell types such as hippocampal and olfactory granule neurons as well as ependymal cells.Interestingly,Nestin tracing also labeled skeletal myocytes,ileal crypt cells,and sparsely marked cerebellar granule neurons.Our findings provide support for endothelial cells as active contributors to adult tissue progenitor pools.This information could be of particular significance for the intravenous delivery of therapeutics to downstream endothelial-derived cellular targets.The animal experiments were approved by the Boise State University Institute Animal Care and Use Committee(approval No.006-AC15-018)on October 31,2018. 相似文献
8.
Molly Orcutt Wendy C. King Melissa A. Kalarchian Michael J. Devlin Marsha D. Marcus Luis Garcia Kristine J. Steffen James E. Mitchell 《Surgery for obesity and related diseases》2019,15(2):295-303
Background
A history of childhood maltreatment and psychopathology are common in adults with obesity.Objectives
To report childhood maltreatment and to evaluate associations between severity and type of childhood maltreatment and lifetime history of psychopathology among adults with severe obesity awaiting bariatric surgery.Setting
Four clinical centers of the Longitudinal Assessment of Bariatric Surgery Research Consortium.Methods
The Childhood Trauma Questionnaire, which assesses presence/severity (i.e., none, mild, moderate, severe) of physical abuse, mental abuse, physical neglect, mental neglect, and sexual abuse, was completed by 302 female and 66 male bariatric surgery patients. Presurgery lifetime history of psychopathology and suicidal ideation/behavior were assessed with the Structured Clinical Interview for DSM-IV and the Suicidal Behavioral Questionnaire-Revised, respectively. Presurgery lifetime history of antidepressant use was self-reported.Results
Two thirds (66.6%) of females and 47.0% of males reported at least 1 form of childhood trauma; 42.4% and 24.2%, respectively, at greater than or equal to moderate severity. Among women, presence/greater severity of childhood mental or physical abuse or neglect was associated with a higher risk of history of psychopathology (i.e., major depressive disorder, posttraumatic stress disorder, other anxiety disorder, alcohol use disorder, binge eating disorder), suicidal ideation/behavior and antidepressant use (P for all ≤ .02). These associations were independent of age, race, education, body mass index, and childhood sexual abuse. Childhood sexual abuse was independently associated with a history of suicidal ideation/behavior and antidepressant use only (P for both ≤ .05). Statistical power was limited to evaluate these associations among men.Conclusion
Among women with obesity, presence/severity of childhood trauma was positively associated with relatively common psychiatric disorders. 相似文献9.
10.
James L. Dorling Alice E. Thackray James A. King Andrea Pucci Fernanda R. Goltz Rachel L. Batterham David J. Stensel 《Nutrients》2020,12(12)
The fat mass and obesity-associated gene (FTO) rs9939609 A-allele is linked to obesity and dyslipidemia, yet the independent influence of this polymorphism on blood lipids remains equivocal. We examined the influence of the FTO rs9939609 polymorphism on fasting and postprandial blood lipids in individuals homozygous for the risk A-allele or T-allele with similar anthropometric and demographic characteristics. 12 AA and 12 TT males consumed a standardized meal after fasting overnight. Blood samples were collected at baseline (−1.5 h), before the meal (0 h), and for five hours postprandially to measure lipid, glucose, and insulin concentrations. Time-averaged total area under the curve (TAUC) values (0–5 h) were calculated and compared between genotypes. Fasting triacylglycerol (TG), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, non-esterified fatty acid (NEFA), glucose, and insulin concentrations were similar between groups (p ≥ 0.293). TAUC for TG was similar in AAs and TTs (95% confidence interval (CI) −0.52 to 0.31 mmol/L/h; p = 0.606). Likewise, TAUC values were similar for NEFA (95% CI −0.04 to 0.03 mmol/L/h; p = 0.734), glucose (95% CI −0.41 to 0.44 mmol/L/h; p = 0.951), and insulin (95% CI −6.87 to 2.83 pmol/L/h; p = 0.395). Blood lipids are not influenced by the FTO rs9939609 polymorphism, suggesting the FTO-dyslipidemia link is mediated by adiposity and weight management is important in preventing FTO-related lipid variations. 相似文献