淫羊藿苷对急性早幼粒白血病细胞体内外效应的研究

目的 :探讨淫羊藿苷 (ICA)对急性早幼粒白血病细胞的诱导分化作用。方法 :采用ICA与全反式维甲酸 (ATRA)对比试验 ,观察ICA在体外及小鼠体内对白血病细胞增殖分化的影响。结果 :ICA在体内外对白血病细胞均有较明显的诱导分化和抑制增殖作用 ,且与ATRA合用可产生明显的协同效应。结论 :ICA具有明显的抗白血病细胞作用     

Serological evaluation of the role of cytomegalovirus in the pathogenesis of IDDM: a prospective study

Summary To study the possible temporal association between primary cytomegalovirus infection and the appearance of islet cell autoantibodies or the development of insulin-dependent diabetes mellitus (IDDM) cytomegalovirus antibodies were analysed from follow-up sera of 46 initially non-diabetic siblings of diabetic children who either manifested clinical IDDM (22 siblings) or turned islet cell antibody positive (24 siblings) during the prospective observation (mean follow-up time 2.9 years). Secondly, cytomegalovirus antibodies were analysed during pregnancy in 96 mothers whose child presented with IDDM before the age of 7 years and in 96 control mothers who gave birth to a non-diabetic child. Thirdly, a case-control series including 90 newly-diagnosed young children with IDDM and their 90 control subjects was analysed. No seroconversions were found in cytomegalovirus antibodies during the follow-up of the 46 siblings indicating no temporal association with islet cell antibody seroconversion or manifestation of clinical diabetes. During the follow-up 17 (37%) siblings were constantly seronegative and 29 (63%) seropositive for cytomegalovirus IgG and there was no difference between islet cell antibody positive and negative siblings. Cytomegalovirus IgG and IgM were not different in pregnant mothers who gave birth to a subsequently diabetic child compared to control mothers, or in newly-diagnosed diabetic children compared to control children. Cytomegalovirus IgA was higher in newly-diagnosed diabetic children than in control children (p<0.005). This difference disappeared when only cytomegalovirus IgG positive individuals were analysed. No correlation was found between islet cell antibodies and cytomegalovirus antibodies in newly-diagnosed diabetic patients. The results do not support the hypothesis that primary cytomegalovirus infections could initiate the cascade leading to autoimmune destruction of the beta cells.Abbreviations IDDM Insulin-dependent diabetes mellitus - ICA islet cell autoantibodies - CMV cytomegalovirus - EIA enzyme immunoassay - EIU enzyme immunoassay unit     

Reliability and spatial specificity of rat brain sensorimotor functional connectivity networks are superior under sedation compared with general anesthesia

Functional connectivity networks derived from resting‐state functional MRI (rsfMRI) have received increasing interest to further our understanding of brain function. The anesthesia in rodent models may influence the interpretation and comparison of results from functional connectivity MRI (fcMRI). More research is required on this aspect. In this study, we investigated rat brain connectivity networks under 1.5% isoflurane anesthesia in comparison with medetomidine sedation. rsfMRI data were acquired under both anesthesia conditions within one imaging session. Male Wistar rats (n = 17) were scanned at 11.7 T with focus on the sensorimotor system. The data underwent a per‐subject independent component analysis (ICA), after which individual components were grouped using hierarchical clustering. Consistent and reliable networks were identified under medetomidine in sensorimotor cortex (three networks) and striatum (two networks). The incidence of these networks was drastically reduced under isoflurane. Seed correlation analysis confirmed these results and revealed globally elevated correlations with low topical specificity under isoflurane, stemming from low‐frequency global signal fluctuations. Global signal removal thus enhanced slightly regional specificity under isoflurane and showed anti‐correlations of cortico‐striatal connections in both anesthesia regimes. Functional connectivity networks are thus reliably detected in medetomidine‐sedated animals on an individual basis using ICA. Their occurrence, however, is heavily compromised under isoflurane as a result of global signal fluctuations potentially stemming from burst‐suppression‐like neural activity. Anesthesia and pharmacologically induced modulations may provide insight into network mechanisms in the future. As an agent for fcMRI in brain disease studies, light sedation using medetomidine preserves connectivity networks in a greater level of detail, and may therefore be considered superior to standard isoflurane anesthesia. Copyright © 2013 John Wiley & Sons, Ltd.     

Application of Independent Component Analysis for the Data Mining of Simultaneous Eeg–fMRI: Preliminary Experience on Sleep Onset

The simultaneous acquisition of electroencephalogram (EEG) and functional MRI (fMRI) signals is potentially advantageous because of the superior resolution that is achieved in both the temporal and spatial domains, respectively. However, ballistocardiographic artifacts along with ocular artifacts are a major obstacle for the detection of the EEG signatures of interest. Since the sources corresponding to these artifacts are independent from those producing the EEG signatures, we applied the Infomax-based independent component analysis (ICA) technique to separate the EEG signatures from the artifacts. The isolated EEG signatures were further utilized to model the canonical hemodynamic response functions (HRFs). Subsequently, the brain areas from which these EEG signatures originated were identified as locales of activation patterns from the analysis of fMRI data. Upon the identification and subsequent evaluation of brain areas generating interictal epileptic discharge (IED) spikes from an epileptic subject, the presented method was successfully applied to detect the theta and alpha rhythms that are sleep onset-related EEG signatures along with the subsequent neural circuitries from a sleep-deprived volunteer. These results suggest that the ICA technique may be useful for the preprocessing of simultaneous EEG–fMRI acquisitions, especially when a reference paradigm is unavailable.     

The effect of model order selection in group PICA

Independent component analysis (ICA) of functional MRI data is sensitive to model order selection. There is a lack of knowledge about the effect of increasing model order on independent components' (ICs) characteristics of resting state networks (RSNs). Probabilistic group ICA (group PICA) of 55 healthy control subjects resting state data was repeated 100 times using ICASSO repeatability software and after clustering of components, centrotype components were used for further analysis. Visual signal sources (VSS), default mode network (DMN), primary somatosensory (S₁), secondary somatosensory (S₂), primary motor cortex (M₁), striatum, and precuneus (preC) components were chosen as components of interest to be evaluated by varying group probabilistic independent component analysis (PICA) model order between 10 and 200. At model order 10, DMN and VSS components fuse several functionally separate sources that at higher model orders branch into multiple components. Both volume and mean z‐score of components of interest showed significant (P < 0.05) changes as a function of model order. In conclusion, model order has a significant effect on ICs characteristics. Our findings suggest that using model orders ≤20 provides a general picture of large scale brain networks. However, detection of some components (i.e., S₁, S₂, and striatum) requires higher model order estimation. Model orders 30–40 showed spatial overlapping of some IC sources. Model orders 70 ± 10 offer a more detailed evaluation of RSNs in a group PICA setting. Model orders > 100 showed a decrease in ICA repeatability, but added no significance to either volume or mean z‐score results. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Bilateral ethmoidal dural arteriovenous fistula: Unexpected surgical diagnosis

Dural arteriovenous fistulae (DAVFs) are infrequent lesions, the most common locations of which are the cavernous, sigmoid and transverse sinuses. The cribiform plate is one of the less frequent sites for DAVFs, where they entail a high hemorrhage risk. Feeding arteries for ethmoidal DAVFs can be uni- or bilateral. However, the draining fistulous system has classically been described as unilateral. The authors report the second case in literature of bilateral ethmoidal DAVF, which is defined as that with bilateral draining veins. The present case was diagnosed only after surgical exploration of both cribiform plates. No preoperative radiological test could detect the presence of a bilateral venous draining system from the ethmoidal DAVF. Possible reasons for that lack of presurgical diagnosis are discussed. Bilateral surgical exploration of the anterior cranial fossa is recommended when dealing with ethmoidal DAVFs, even when they seem to be unilateral on preoperative studies.     

Functional parcellation of the inferior frontal and midcingulate cortices in a flanker‐stop‐change paradigm

Conflict monitoring and motor inhibition are engaged in the performance of complex tasks. The midcingulate cortex (MCC) has been suggested to detect conflicts, whereas the right inferior frontal cortex (IFC) seems to be of relevance for the inhibition process. The current experiment investigates the neural underpinnings of their interplay via a modified flanker paradigm. Conflict was manipulated by the congruency of flanking stimuli relative to a target (congruent vs. incongruent) and motor inhibition by a within‐trial response change of the initiated response (keep response vs. stop‐change). We used event‐related functional magnetic resonance imaging, decomposition with high model order ICA, and single trial analysis to derive a functional parcellation of the whole‐brain data. Results demonstrate the segmentation of the MCC into anterior and posterior subregions, and of the IFC into the pars opercularis, pars triangularis, and pars orbitalis. The pars opercularis and pars triangularis of the right IFC constituted the foundation of inhibition‐related networks. With high conflict on incongruent trials, activity in the posterior MCC network, as well as in one right IFC network was observed. Stop‐change trials modulated both the MCC as well as networks covering extended parts of the IFC. Whereas conflict processing and inhibition most often are studied separately, this study provides a synopsis of functionally coupled brain regions acting in concert to enable an optimal performance in situations involving interference and inhibition. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Perception-action integration during inhibitory control is reflected in a concomitant multi-region processing of specific codes in the neurophysiological signal

The integration of perception and action has long been studied in psychological science using overarching cognitive frameworks. Despite these being very successful in explaining perception-action integration, little is known about its neurophysiological and especially the functional neuroanatomical foundations. It is unknown whether distinct brain structures are simultaneously involved in the processing of perception-action integration codes and also to what extent demands on perception-action integration modulate activities in these structures. We investigate these questions in an EEG study integrating temporal and ICA-based EEG signal decomposition with source localization. For this purpose, we used data from 32 healthy participants who performed a ‘TEC Go/Nogo’ task. We show that the EEG signal can be decomposed into components carrying different informational aspects or processing codes relevant for perception-action integration. Importantly, these specific codes are processed independently in different brain structures, and their specific roles during the processing of perception-action integration differ. Some regions (i.e., the anterior cingulate and insular cortex) take a ‘default role’ because these are not modulated in their activity by demands or the complexity of event file coding processes. In contrast, regions in the motor cortex, middle frontal, temporal, and superior parietal cortices were not activated by ‘default’ but revealed modulations depending on the complexity of perception-action integration (i.e., whether an event file has to be reconfigured). Perception-action integration thus reflects a multi-region processing of specific fractions of information in the neurophysiological signal. This needs to be taken into account when further developing a cognitive science framework detailing perception-action integration.     

Comparison of non-contrast vessel wall imaging and 3-D time-of-flight MRA for atherosclerotic stenosis and plaque characterization within intracranial arteries

PurposeWe compared the ability of intracranial high-resolution vessel wall imaging (VWI) without gadolinium and 3-D time-of-flight (3D-TOF) MRA techniques to characterize intracranial arterial stenosis and arterial wall plaque consistent with atherosclerotic plaque.MethodsConsecutive intracranial VWI examinations performed within 2 months of a 3D-TOF exam with at least 1 noted plaque was included. Examinations assessed 17 vessel segments for plaque and diameters of stenotic and normal segments using double oblique reformatted images. Results were compared with the VWI and 3D-TOF exams considered the reference standard for plaque and luminal stenosis, respectively.ResultsAssessed segments totaled 286 from 17 patients. Proximal segment sensitivity and specificity for luminal stenosis detection with VWI was 92.5% and 82.1%, respectively, whereas for assessing plaque with 3D-TOF it was 59.4% and 98.3%, respectively. The mean intra-rater difference in luminal diameter measurements between VWI and 3D-TOF at normal segments and at the area of maximal stenosis was 0.02 mm (SD 0.51 mm) and 0.08 mm (SD 0.66 mm), respectively.ConclusionsIntracranial VWI demonstrated reasonably high sensitivity and specificity for luminal stenosis assessment using 3D-TOF as a reference standard, while 3D-TOF demonstrated low sensitivity for plaque detection. Our results suggest that VWI can be used for simultaneous assessment of luminal stenosis and plaque in the intracranial arteries.     

Age governs gender-dependent islet cell autoreactivity and predicts the clinical course in childhood IDDM

Most IDDM patients temporarily restore some of their beta-cell function following the initiation of insulin therapy. The aim of this study was to analyse the influence of age, gender, metabolic state at diagnosis and presence of autoantibodies (GAD65 antibodies and IC A) on the duration of the clinical partial remission. In total, 149 consecutively diagnosed IDDM children, 0–16 y old (70F, 79M, mean age 9. 5 y) were studied. Partial remission was arbitrarily defined as the period when the insulin dose was below 0. 5 U/BW 24h^-1 and HbA1c below 7. 5%, and occurred in 119/149 patients with a duration between 1 and 38 months. Cox's regression analysis showed that the factors significantly associated with the duration of remission were age, gender, interaction between age and gender, ICA and a high initial HbAlc, whereas GAD65Ab had no influence. Young boys had the shortest remission period, while adolescent boys had the longest, as compared to young and adolescent girls. The IC A-negative patients ( n = 42) had a longer remission period (median 9. 7 months) than the ICA-positive children ( n = 107; 5. 0 months; p = 0. 0001), regardless of GAD65Ab status. We speculate that the relative insulin resistance, which is more pronounced in pubertal girls than in boys, may be associated with a more rapid increase of exogenous insulin requirement. These findings are important when evaluating the effect of islet cell autoreactivity on the clinical course of IDDM in children.