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Nicole A. Weitz M.D. Christine T. Lauren M.D. Gerald G. Behr M.D. June K. Wu M.D. Jessica J. Kandel M.D. Philip M. Meyers M.D. Sally Sultan M.D. Kwame Anyane‐Yeboa M.D. Kimberly D. Morel M.D. Maria C. Garzon M.D. 《Pediatric dermatology》2015,32(1):76-84
Capillary malformation–arteriovenous malformation syndrome (CM‐AVM) is an autosomal dominant disorder caused by RASA1 mutations. The prevalence and phenotypic spectrum are unknown. Evaluation of patients with multiple CMs is challenging because associated AVMs can be life threatening. The objective of this study was to describe the clinical characteristics of children presenting with features of CM‐AVM to an academic pediatric dermatology practice. After institutional review board approval was received, a retrospective chart review was performed of patients presenting between 2009 and 2012 with features of CM‐AVM. We report nine cases. Presenting symptoms ranged from extensive vascular stains and cardiac failure to CMs noted incidentally during routine skin examination. All demonstrated multiple CMs, two had Parkes Weber syndrome, and two had multiple infantile hemangiomas. Seven patients had family histories of multiple CMs; three had family histories of large, atypical CMs. Six had personal or family histories of AVMs. Genetic evaluation was recommended for all and was pursued by six families; four RASA1 mutations were identified, including one de novo. Consultations with neurology, cardiology, and orthopedics were recommended. Most patients (89%) have not required treatment to date. CM‐AVM is an underrecognized condition with a wide clinical spectrum that often presents in childhood. Further evaluation may be indicated in patients with multiple CMs. This study is limited by its small and retrospective nature. 相似文献
33.
PURPOSE OF REVIEW: Though long hypothesized, the putative link between Mycobacterium avium paratuberculosis and Crohn's disease remains neither confirmed nor refuted. This article reviews published contributions that directly or indirectly address this question. RECENT FINDINGS: Epidemiologic studies, looking for M. avium paratuberculosis DNA in Crohn's tissue, show a strong association between the agent and this disease. Supporting data, however, are presently inconclusive on a causal role. Genetic studies provide indirect support for a role of mycobacteria in Crohn's disease, by identifying susceptibility genes that encode proteins implicated in innate immunity to intracellular bacteria. Clinical trial data support at least a short-term benefit for antimycobacterial therapy in Crohn's disease, but the microbial specificity of this response is presently unknown. SUMMARY: There appears to be a strong association between M. avium paratuberculosis and Crohn's disease, but the causality of this association is unknown. Consequently, the therapeutic implications of this association require further study. A number of critical questions about the biology of M. avium paratuberculosis remain unanswered. Data from studies of this organism, and its interaction with the immune system, can help address proposed reasons for or against a role of M. avium paratuberculosis in the etiology of Crohn's disease. 相似文献
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Corticosterone and corticotropin‐releasing factor acutely facilitate gamma oscillations in the hippocampus in vitro 下载免费PDF全文
Gürsel Çalışkan Steffen B. Schulz David Gruber Joachim Behr Uwe Heinemann Zoltan Gerevich 《The European journal of neuroscience》2015,41(1):31-44
Stressful experiences do not only cause peripheral changes in stress hormone levels, but also affect central structures such as the hippocampus, implicated in spatial orientation, stress evaluation, and learning and memory. It has been suggested that formation of memory traces is dependent on hippocampal gamma oscillations observed during alert behaviour and rapid eye movement sleep. Furthermore, during quiescent behaviour, sharp wave‐ripple (SW‐R) activity emerges. These events provide a temporal window during which reactivation of memory ensembles occur. We hypothesized that stress‐responsive modulators, such as corticosterone (CORT), corticotropin‐releasing factor (CRF) and the neurosteroid 3α, 21‐dihydroxy‐5α‐pregnan‐20‐one (THDOC) are able to modulate gamma oscillations and SW‐Rs. Using in vitro hippocampal slices, we studied acute and subacute (2 h) impact of these agents on gamma oscillations in area cornu ammonis 3 of the ventral hippocampus induced by acetylcholine (10 μm ) combined with physostigmine (2 μm ). CORT increased the gamma oscillations in a dose‐dependent fashion. This effect was mediated by glucocorticoid receptors. Likewise, CRF augmented gamma oscillations via CRF type 1 receptor. Lastly, THDOC was found to diminish cholinergic gamma oscillations in a dose‐dependent manner. Neither CORT, CRF nor THDOC modulated gamma power when pre‐applied for 1 h, 2 h before the induction of gamma oscillations. Interestingly, stress‐related neuromodulators had rather mild effects on spontaneous SW‐R compared with their effects on gamma oscillations. These data suggest that the alteration of hippocampal gamma oscillation strength in vitro by stress‐related agents is an acute process, permitting fast adaptation to new attention‐requiring situations in vivo. 相似文献
35.
It is commonly accepted that the hippocampus is critically involved in the explicit memory formation of mammals. The subiculum is the principal target of CA1 pyramidal cells and thus serves as the major relay station for the outgoing hippocampal information. Pyramidal cells in the subiculum can be classified according to their firing properties into burst-spiking and regular-spiking cells. In the present study we demonstrate that burst-spiking and regular-spiking cells show fundamentally different forms of low frequency-induced synaptic plasticity in rats. In burst-spiking cells, low-frequency stimulation (at 0.5–5 Hz) induces frequency-dependent long-term depression (LTD) with a maximum at 1 Hz. This LTD is dependent on the activation of NMDAR and masks an mGluR-dependent long-term potentiation (LTP). In contrast, in regular-spiking cells low-frequency stimulation induces an mGluR-dependent LTP that masks an NMDAR-dependent LTD. Both processes depend on postsynaptic Ca2+ -signaling as BAPTA prevents the induction of synaptic plasticity in both cell types. Thus, mGluR-dependent LTP and NMDAR-dependent LTD occur simultaneously at CA1-subiculum synapses and the predominant direction of synaptic plasticity relies on the cell type investigated. Our data indicate a novel mechanism for the sliding-threshold model of synaptic plasticity, in which induction of LTP and LTD seems to be driven by the relative activation state of NMDAR and mGluR. Our observation that the direction of synaptic plasticity correlates with the discharge properties of the postsynaptic cell reveals a novel and intriguing mechanism of target specificity that may serve in tuning the significance of neuronal information by trafficking hippocampal output onto either subicular burst-spiking or regular-spiking cells. 相似文献
36.
Isolation of the genome sequence strain Mycobacterium avium 104 from multiple patients over a 17-year period 下载免费PDF全文
Horan KL Freeman R Weigel K Semret M Pfaller S Covert TC van Soolingen D Leão SC Behr MA Cangelosi GA 《Journal of clinical microbiology》2006,44(3):783-789
The genome sequence strain 104 of the opportunistic pathogen Mycobacterium avium was isolated from an adult AIDS patient in Southern California in 1983. Isolates of non-paratuberculosis M. avium from 207 other patients in Southern California and elsewhere were examined for genotypic identity to strain 104. This process was facilitated by the use of a novel two-step approach. In the first step, all 208 strains in the sample were subjected to a high-throughput, large sequence polymorphism (LSP)-based genotyping test, in which DNA from each strain was tested by PCR for the presence or absence of 4 hypervariable genomic regions. Nineteen isolates exhibited an LSP type that resembled that of strain 104. This subset of 19 isolates was then subjected to high-resolution repetitive sequence-based PCR typing, which identified 10 isolates within the subset that were genotypically identical to strain 104. These isolates came from 10 different patients at 5 clinical sites in the western United States, and they were isolated over a 17-year time span. Therefore, the sequenced genome of M. avium strain 104 has been associated with disease in multiple patients in the western United States. Although M. avium is known for its genetic plasticity, these observations also show that strains of the pathogen can be genotypically stable over extended time periods. 相似文献
37.
Evaluation of in situ methods used to detect Mycobacterium avium subsp. paratuberculosis in samples from patients with Crohn's disease 下载免费PDF全文
Jeyanathan M Alexander DC Turenne CY Girard C Behr MA 《Journal of clinical microbiology》2006,44(8):2942-2950
In common with other diagnostic tests, detection of mycobacteria in tissue by microscopic examination is susceptible to spectrum bias. Since Crohn's disease is defined by the absence of detectable pathogenic organisms, the use of in situ techniques to search for Mycobacterium avium subsp. paratuberculosis in Crohn's disease samples requires validation of methods in a paucibacillary setting. To generate paucibacillary infection, C57BL/6 mice were artificially infected with Mycobacterium avium subsp. paratuberculosis strain K10 and M. tuberculosis H37Rv, yielding tissues harboring fewer than one bacillus per oil immersion field. Serial sections of organs were then studied by cell wall-based staining techniques (Ziehl-Neelsen and auramine rhodamine) and nucleic acid-based staining techniques (in situ hybridization [ISH] and indirect in situ PCR [IS PCR]). Microscopic examination and measurement of morphometric parameters of bacilli revealed that for all methods, Mycobacterium avium subsp. paratuberculosis bacilli were observed to be shorter, smaller, and less rod shaped than M. tuberculosis bacilli. Ziehl-Neelsen, auramine rhodamine stains, ISH targeting rRNA, and IS-PCR targeting the IS900 element afforded comparable sensitivities, but for all methods, visualization of individual bacterial forms required magnification x1,000. Auramine rhodamine staining and IS-PCR generated positive signals in negative controls, indicating the nonspecificity of these assays. Together, our results indicate that detection of Mycobacterium avium subsp. paratuberculosis bacilli in tissue requires oil immersion microscopy, that rRNA-ISH provides sensitivity and specificity comparable to those of Ziehl-Neelsen staining, and that the microscopic detection limit for Mycobacterium avium subsp. paratuberculosis in tissue is governed more by bacterial burden than by staining method. 相似文献
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40.
Microevolution of the direct repeat region of Mycobacterium tuberculosis: implications for interpretation of spoligotyping data 下载免费PDF全文
Warren RM Streicher EM Sampson SL van der Spuy GD Richardson M Nguyen D Behr MA Victor TC van Helden PD 《Journal of clinical microbiology》2002,40(12):4457-4465
The direct repeat (DR) region has been determined to be an important chromosomal domain for studying the evolution of Mycobacterium tuberculosis. Despite this, very little is known about microevolutionary events associated with clonal expansion and how such events influence the interpretation of both restriction fragment length polymorphism (RFLP) and spoligotype data. This study examined the structure of the DR region in three independently evolving lineages of M. tuberculosis with a combination of DR-RFLP, spoligotyping, and partial DNA sequencing. The results show that the duplication of direct variable repeat (DVR) sequences and single-nucleotide polymorphisms is rare; conversely, the deletion of DVR sequences and IS6110-mediated mutation is observed frequently. Deletion of either single or contiguous DVR sequences was observed. The deletion of adjacent DVR sequences occurred in a dependent manner rather than as an accumulation of independent events. Insertion of IS6110 into either the direct repeat or spacer sequences influenced the spoligotype pattern, resulting in apparent deletion of DVR sequences. Homologous recombination between adjacent IS6110 elements led to extensive deletion in the DR region, again demonstrating a dependent evolutionary mechanism. Different isolates from the same strain family and isolates from different strain families were observed to converge to the same spoligotype pattern. In conclusion, the binary data of the spoligotype are unable to provide sufficient information to accurately establish genotypic relationships between certain clinical isolates of M. tuberculosis. This has important implications for molecular epidemiologic strain tracking and for the application of spoligotype data to phylogenetic analysis of M. tuberculosis isolates. 相似文献