Evidence for a vascular contribution to diffusion FMRI at high b value

Recent work has suggested that diffusion-weighted functional magnetic resonance imaging (FMRI) with strong diffusion weighting (high b value) detects neuronal swelling that is directly related to neuronal firing. This would constitute a much more direct measure of brain activity than current methods and represent a major advance in neuroimaging. However, it has not been firmly established that the observed signal changes do not reflect residual vascular effects, which are known to exist at low b value. This study measures the vascular component of diffusion FMRI directly by using hypercapnia, which induces blood flow changes in the absence of a change in neuronal firing. Hypercapnia elicits a similar diffusion FMRI response to a visual stimulus including a rise in percent signal change with increasing b value, which was reported for visual activation. Analysis of the response timing found no evidence for an early response at high b value, which has been reported as evidence for a nonhemodynamic response. These results suggest that a large component of the diffusion FMRI signal at high b value is vascular rather than neuronal.     

Functional diffusion map: a noninvasive MRI biomarker for early stratification of clinical brain tumor response

Assessment of radiation and chemotherapy efficacy for brain cancer patients is traditionally accomplished by measuring changes in tumor size several months after therapy has been administered. The ability to use noninvasive imaging during the early stages of fractionated therapy to determine whether a particular treatment will be effective would provide an opportunity to optimize individual patient management and avoid unnecessary systemic toxicity, expense, and treatment delays. We investigated whether changes in the Brownian motion of water within tumor tissue as quantified by using diffusion MRI could be used as a biomarker for early prediction of treatment response in brain cancer patients. Twenty brain tumor patients were examined by standard and diffusion MRI before initiation of treatment. Additional images were acquired 3 weeks after initiation of chemo- and/or radiotherapy. Images were coregistered to pretreatment scans, and changes in tumor water diffusion values were calculated and displayed as a functional diffusion map (fDM) for correlation with clinical response. Of the 20 patients imaged during the course of therapy, 6 were classified as having a partial response, 6 as stable disease, and 8 as progressive disease. The fDMs were found to predict patient response at 3 weeks from the start of treatment, revealing that early changes in tumor diffusion values could be used as a prognostic indicator of subsequent volumetric tumor response. Overall, fDM analysis provided an early biomarker for predicting treatment response in brain tumor patients.     

Spontaneous cortical activity in awake monkeys composed of neuronal avalanches

Spontaneous neuronal activity is an important property of the cerebral cortex but its spatiotemporal organization and dynamical framework remain poorly understood. Studies in reduced systems—tissue cultures, acute slices, and anesthetized rats—show that spontaneous activity forms characteristic clusters in space and time, called neuronal avalanches. Modeling studies suggest that networks with this property are poised at a critical state that optimizes input processing, information storage, and transfer, but the relevance of avalanches for fully functional cerebral systems has been controversial. Here we show that ongoing cortical synchronization in awake rhesus monkeys carries the signature of neuronal avalanches. Negative LFP deflections (nLFPs) correlate with neuronal spiking and increase in amplitude with increases in local population spike rate and synchrony. These nLFPs form neuronal avalanches that are scale-invariant in space and time and with respect to the threshold of nLFP detection. This dimension, threshold invariance, describes a fractal organization: smaller nLFPs are embedded in clusters of larger ones without destroying the spatial and temporal scale-invariance of the dynamics. These findings suggest an organization of ongoing cortical synchronization that is scale-invariant in its three fundamental dimensions—time, space, and local neuronal group size. Such scale-invariance has ontogenetic and phylogenetic implications because it allows large increases in network capacity without a fundamental reorganization of the system.     

Anatomical accuracy of brain connections derived from diffusion MRI tractography is inherently limited

Tractography based on diffusion-weighted MRI (DWI) is widely used for mapping the structural connections of the human brain. Its accuracy is known to be limited by technical factors affecting in vivo data acquisition, such as noise, artifacts, and data undersampling resulting from scan time constraints. It generally is assumed that improvements in data quality and implementation of sophisticated tractography methods will lead to increasingly accurate maps of human anatomical connections. However, assessing the anatomical accuracy of DWI tractography is difficult because of the lack of independent knowledge of the true anatomical connections in humans. Here we investigate the future prospects of DWI-based connectional imaging by applying advanced tractography methods to an ex vivo DWI dataset of the macaque brain. The results of different tractography methods were compared with maps of known axonal projections from previous tracer studies in the macaque. Despite the exceptional quality of the DWI data, none of the methods demonstrated high anatomical accuracy. The methods that showed the highest sensitivity showed the lowest specificity, and vice versa. Additionally, anatomical accuracy was highly dependent upon parameters of the tractography algorithm, with different optimal values for mapping different pathways. These results suggest that there is an inherent limitation in determining long-range anatomical projections based on voxel-averaged estimates of local fiber orientation obtained from DWI data that is unlikely to be overcome by improvements in data acquisition and analysis alone.The creation of a comprehensive map of the connectional neuroanatomy of the human brain would be a fundamental achievement in neuroscience. However, despite the numerous efforts to date (for a historical review, see ref. 1), creating this map remains a challenge. A major limitation is that the current gold-standard technique for mapping structural connections, which requires the injection of axonal tracers, cannot be used in humans. The introduction of diffusion-weighted MRI (DWI) (2–4) and the subsequent advent of diffusion tensor MRI (DTI) (5) opened the possibility of exploring the structural properties of white matter in the living human brain (6). Local DWI measures are used clinically for the early detection of stroke and for the characterization of neurological disorders such as multiple sclerosis, epilepsy, and brain gliomas, among others (7). In addition, tractography approaches (8–12) that can infer structural brain connectivity based on brain-wide local DWI measurement have been developed (for reviews, see refs. 13 and 14). The success of DWI tractography as a method for studying fiber trajectories has led to a systematic characterization of large white-matter pathways of the living human brain (e.g., ref. 15), and now it is used routinely to provide a structural explanation for aspects of human brain function (16).A major limitation of DWI tractography is that its characterization of axonal pathways is based on indirect information and numerous assumptions. Local white matter orientation profiles are based on the statistical displacement profile (i.e., diffusion propagator) of water molecules in brain tissue on the coarse scale of a voxel, and fiber trajectories are inferred based on the adjacency of similar diffusion profiles. This approach differs fundamentally from conventional tract-tracing approaches in animals, which involve the physical transport of traceable molecules through the cells’ axoplasm over a large distance. Because these molecules occupy positions within the axon, it sometimes is possible to reconstruct the trajectory of individual neurons through the white matter (e.g., ref. 17). Given the inherent coarseness of DWI tractography, it can be argued that the prospect of using this method to reconstruct complex axonal pathways accurately in the human brain, in a manner similar to that used for molecular tracers in animals, is likely to be intrinsically problematic. Indeed, the limitations of DWI tractography techniques have been noted since their inception (8), and the anatomical accuracy of results from tractography based on the tensor model has been shown to be mixed (18). This inaccuracy has been attributed to two main factors. The first relates to the assumptions underlying tractography algorithms. For example, it has long been recognized that a simple tensor model (19) of local diffusion leads to problems in certain white matter regions where fibers cross within individual voxels. As a remedy, high angular resolution diffusion imaging (HARDI) methods (e.g., refs. 20–24) have been developed to enable better characterization of the diffusion displacement profile and to improve the accuracy of tractography. The second factor limiting accuracy stems from the low quality of clinical DWI data because of various sources of noise. Eddy current distortions, subject motion, physiological noise (see ref. 25 for a review), and susceptibility artifacts from echo planar imaging (EPI) (26) all lead to poor local characterization of diffusion and, consequently, to incorrect tractography results. Continuing advances in sequence design, MRI gradient hardware, and postprocessing correction schemes have overcome many of the initial problems (27) and have led to the belief that further acquisition improvements will result in more precise mapping of structural connections in the human brain (28). In fact, the assumption underlying many recent initiatives to map structural brain connectivity from DWI data is that improved image data quality and sophisticated diffusion modeling approaches will result in anatomically accurate maps of white matter connections (29). The goal of the present study is to investigate the validity of this assumption.To achieve this goal, we acquired high angular resolution DWI data from a normal adult rhesus macaque brain, ex vivo, at a spatial resolution of 250 microns (isotropic). This dataset is ideal for exploring the limits of DWI tractography because of its high signal-to-noise ratio (SNR) (for SNR computation, see SI Materials and Methods) and the almost complete absence of experimental confounds and artifacts such as those originating from patient motion, noise, cardiac pulsation, and EPI distortion that are typically encountered in in vivo studies. Using the axonal tracer results from a well-known atlas (17) as reference, we measured the sensitivity (i.e., the ability to detect true connections) and specificity (i.e., the ability to avoid false connections) of several DWI tractography implementations representative of the current state of the art. This approach allowed us to investigate whether sophisticated diffusion modeling techniques, when applied to DWI data of exceptional quality, would yield accurate maps of axonal connections.     

Spatially clustered neuronal assemblies comprise the microstructure of synchrony in chronically epileptic networks

Epilepsy is characterized by recurrent synchronizations of neuronal activity, which are both a cardinal clinical symptom and a debilitating phenomenon. Although the temporal dynamics of epileptiform synchronizations are well described at the macroscopic level using electrophysiological approaches, less is known about how spatially distributed microcircuits contribute to these events. It is important to understand the relationship between micro and macro network activity because the various mechanisms proposed to underlie the generation of such pathological dynamics are united by the assumption that epileptic activity is recurrent and hypersynchronous across multiple scales. However, quantitative analyses of epileptiform spatial dynamics with cellular resolution have been hampered by the difficulty of simultaneously recording from multiple neurons in lesioned, adult brain tissue. We have overcome this experimental limitation and used two-photon calcium imaging in combination with a functional clustering algorithm to uncover the functional network structure of the chronically epileptic dentate gyrus in the mouse pilocarpine model of temporal lobe epilepsy. We show that, under hyperexcitable conditions, slices from the epileptic dentate gyrus display recurrent interictal-like network events with a high diversity in the activity patterns of individual neurons. Analysis reveals that multiple functional clusters of spatially localized neurons comprise epileptic networks, and that network events are composed of the coactivation of variable subsets of these clusters, which show little repetition between events. Thus, these interictal-like recurrent macroscopic events are not necessarily recurrent when viewed at the microcircuit scale and instead display a patterned but variable structure.     

Delayed after depolarization-mediated triggered activity associated with slow calcium sequestration near the endocardium

INTRODUCTION: Previously, we have shown that cells near the endocardium are more prone to elevated diastolic intracellular calcium levels than cells near the epicardium. The arrhythmogenic consequence of such regional differences in calcium handling is not clear. METHODS AND RESULTS: Using optical mapping techniques, calcium transients and action potentials were recorded simultaneously from ventricular sites across the transmural wall of the arterially perfused canine left ventricular wedge preparation during control conditions, and under conditions of increased calcium entry (I(K) blockade and beta-adrenergic stimulation). Under conditions of enhanced calcium entry, the decay of the calcium transient and diastolic calcium levels during rapid pacing were slower (38%, P < 0.01) and higher (215%, P < 0.02), respectively, near (within approximately 3 mm) the endocardium compared to the epicardium (n = 9). Immediately after termination of rapid pacing under conditions of increased calcium entry, ectopic activity and simultaneous delayed after depolarizations and spontaneous calcium release events were observed. Over all experiments, ectopic activity occurred more frequently closer to the endocardium compared to the epicardium. CONCLUSIONS: Under conditions of enhanced calcium entry, myocytes closer to the endocardium exhibit a higher level of diastolic calcium and greater ectopic activity compared to the epicardium. We show for the first time simultaneous delayed after depolarization and spontaneous calcium release events from myocytes in a normally coupled multicellular preparation. These data combined suggest that myocytes near the endocardium are more susceptible to calcium-mediated triggered activity.     

Calpain cleaves and activates the TRPC5 channel to participate in semaphorin 3A-induced neuronal growth cone collapse

The nonselective cation channel transient receptor potential canonical (TRPC)5 is found predominantly in the brain and has been proposed to regulate neuronal processes and growth cones. Here, we demonstrate that semaphorin 3A-mediated growth cone collapse is reduced in hippocampal neurons from TRPC5 null mice. This reduction is reproduced by inhibition of the calcium-sensitive protease calpain in wild-type neurons but not in TRPC5(-/-) neurons. We show that calpain-1 and calpain-2 cleave and functionally activate TRPC5. Mutation of a critical threonine at position 857 inhibits calpain-2 cleavage of the channel. Finally, we show that the truncated TRPC5 predicted to result from calpain cleavage is functionally active. These results indicate that semaphorin 3A initiates growth cone collapse via activation of calpain that in turn potentiates TRPC5 activity. Thus, TRPC5 acts downstream of semaphorin signaling to cause changes in neuronal growth cone morphology and nervous system development.     

From the Cover: Visually evoked activity in cortical cells imaged in freely moving animals

We describe a miniaturized head-mounted multiphoton microscope and its use for recording Ca²⁺ transients from the somata of layer 2/3 neurons in the visual cortex of awake, freely moving rats. Images contained up to 20 neurons and were stable enough to record continuously for >5 min per trial and 20 trials per imaging session, even as the animal was running at velocities of up to 0.6 m/s. Neuronal Ca²⁺ transients were readily detected, and responses to various static visual stimuli were observed during free movement on a running track. Neuronal activity was sparse and increased when the animal swept its gaze across a visual stimulus. Neurons showing preferential activation by specific stimuli were observed in freely moving animals. These results demonstrate that the multiphoton fiberscope is suitable for functional imaging in awake and freely moving animals.     

MRI联合血清维生素D预测慢性丙型肝炎患者肝纤维化临床价值探讨*

目的 探讨慢性丙型肝炎(CHC)患者MRI检查指标和血清维生素D水平变化的意义。方法 200例CHC患者接受肝活检和MRI检查,测量扩散加权成像(DWI)值,采用ELISA法检测血清维生素D。结果 在200例CHC患者中,经肝穿组织病理学检查,发现存在肝纤维化80例(40.0%);80例存在肝纤维化患者血清维生素D水平为(22.1±12.5) nmol/L,显著低于120例无明显肝纤维化患者的(32.1±13.2) nmol/L(P <0.05);80例肝纤维化患者MRI表观弥散系数(ADC)为(1322.8±82.6),T₁变化率为(0.35±0.17),均显著低于120例无肝纤维化患者的(1542.5±80.7)和(0.52±0.21)。结论 伴有肝纤维化的CHC患者血清维生素D降低,MRI检查显示ADC值和T₁变化率也显著降低,了解这些变化可能对判断肝纤维化有帮助。     

Age-related memory deficits linked to circuit-specific disruptions in the hippocampus

Converging data from rodents and humans have demonstrated an age-related decline in pattern separation abilities (the ability to discriminate among similar experiences). Several studies have proposed the dentate and CA3 subfields of the hippocampus as the potential locus of this change. Specifically, these studies identified rigidity in place cell remapping in similar environments in the CA3. We used high-resolution fMRI to examine activity profiles in the dentate gyrus and CA3 in young and older adults as stimulus similarity was incrementally varied. We report evidence for "representational rigidity" in older adults' dentate/CA3 that is linked to behavioral discrimination deficits. Using ultrahigh-resolution diffusion imaging, we quantified both the integrity of the perforant path as well as dentate/CA3 dendritic changes and found that both were correlated with dentate/CA3 functional rigidity. These results highlight structural and functional alterations in the hippocampal network that predict age-related changes in memory function and present potential targets for intervention.     

Nonthermal ATP-dependent fluctuations contribute to the in vivo motion of chromosomal loci

Chromosomal loci jiggle in place between segregation events in prokaryotic cells and during interphase in eukaryotic nuclei. This motion seems random and is often attributed to brownian motion. However, we show here that locus dynamics in live bacteria and yeast are sensitive to metabolic activity. When ATP synthesis is inhibited, the apparent diffusion coefficient decreases, whereas the subdiffusive scaling exponent remains constant. Furthermore, the magnitude of locus motion increases more steeply with temperature in untreated cells than in ATP-depleted cells. This "superthermal" response suggests that untreated cells have an additional source of molecular agitation, beyond thermal motion, that increases sharply with temperature. Such ATP-dependent fluctuations are likely mechanical, because the heat dissipated from metabolic processes is insufficient to account for the difference in locus motion between untreated and ATP-depleted cells. Our data indicate that ATP-dependent enzymatic activity, in addition to thermal fluctuations, contributes to the molecular agitation driving random (sub)diffusive motion in the living cell.     

Polyamine pathway contributes to the pathogenesis of Parkinson disease

The full complement of molecular pathways contributing to the pathogenesis of Parkinson disease (PD) remains unknown. Here we address this issue by taking a broad approach, beginning by using functional MRI to identify brainstem regions differentially affected and resistant to the disease. Relying on these imaging findings, we then profiled gene expression levels from postmortem brainstem regions, identifying a disease-related decrease in the expression of the catabolic polyamine enzyme spermidine/spermine N1-acetyltransferase 1 (SAT1). Next, a range of studies were completed to support the pathogenicity of this finding. First, to test for a causal link between polyamines and α-synuclein toxicity, we investigated a yeast model expressing α-synuclein. Polyamines were found to enhance the toxicity of α-synuclein, and an unbiased genome-wide screen for modifiers of α-synuclein toxicity identified Tpo4, a member of a family of proteins responsible for polyamine transport. Second, to test for a causal link between SAT1 activity and PD histopathology, we investigated a mouse model expressing α-synuclein. DENSPM (N1, N11-diethylnorspermine), a polyamine analog that increases SAT1 activity, was found to reduce PD histopathology, whereas Berenil (diminazene aceturate), a pharmacological agent that reduces SAT1 activity, worsened the histopathology. Third, to test for a genetic link, we sequenced the SAT1 gene and a rare but unique disease-associated variant was identified. Taken together, the findings from human patients, yeast, and a mouse model implicate the polyamine pathway in PD pathogenesis.     

Lack of the endosomal SNAREs vti1a and vti1b led to significant impairments in neuronal development

Fusion between membranes is mediated by specific SNARE complexes. Here we report that fibroblasts survive the absence of the trans-Golgi network/early endosomal SNARE vti1a and the late endosomal SNARE vti1b with intact organelle morphology and minor trafficking defects. Because vti1a and vti1b are the only members of their SNARE subclass and the yeast homolog Vti1p is essential for cell survival, these data suggest that more distantly related SNAREs acquired the ability to function in endosomal traffic during evolution. However, absence of vti1a and vti1b resulted in perinatal lethality. Major axon tracts were missing, reduced in size, or misrouted in Vti1a(-/-) Vti1b(-/-) embryos. Progressive neurodegeneration was observed in most Vti1a(-/-) Vti1b(-/-) peripheral ganglia. Neurons were reduced by more than 95% in Vti1a(-/-) Vti1b(-/-) dorsal root and geniculate ganglia at embryonic day 18.5. These data suggest that special demands for endosomal membrane traffic could not be met in Vti1a(-/-) Vti1b(-/-) neurons. Vti1a(-/-) and Vti1b(-/-) single deficient mice were viable without these neuronal defects, indicating that they can substitute for each other in these processes.     

Long-term effects of marijuana use on the brain

Questions surrounding the effects of chronic marijuana use on brain structure continue to increase. To date, however, findings remain inconclusive. In this comprehensive study that aimed to characterize brain alterations associated with chronic marijuana use, we measured gray matter (GM) volume via structural MRI across the whole brain by using voxel-based morphology, synchrony among abnormal GM regions during resting state via functional connectivity MRI, and white matter integrity (i.e., structural connectivity) between the abnormal GM regions via diffusion tensor imaging in 48 marijuana users and 62 age- and sex-matched nonusing controls. The results showed that compared with controls, marijuana users had significantly less bilateral orbitofrontal gyri volume, higher functional connectivity in the orbitofrontal cortex (OFC) network, and higher structural connectivity in tracts that innervate the OFC (forceps minor) as measured by fractional anisotropy (FA). Increased OFC functional connectivity in marijuana users was associated with earlier age of onset. Lastly, a quadratic trend was observed suggesting that the FA of the forceps minor tract initially increased following regular marijuana use but decreased with protracted regular use. This pattern may indicate differential effects of initial and chronic marijuana use that may reflect complex neuroadaptive processes in response to marijuana use. Despite the observed age of onset effects, longitudinal studies are needed to determine causality of these effects.The rate of marijuana use has had a steady increase since 2007 (1). Among >400 chemical compounds, marijuana’s effects are primarily attributed to δ-9-tetrahydrocannabinol (THC), which is the main psychoactive ingredient in the cannabis plant. THC binds to cannabinoid receptors, which are ubiquitous in the brain. Consequently, exposure to THC leads to neural changes affecting diverse cognitive processes. These changes have been observed to be long-lasting, suggesting that neural changes due to marijuana use may affect neural architecture (2). However, to date, these brain changes as a result of marijuana use remains equivocal. Specifically, although functional changes have been widely reported across cognitive domains in both adult and adolescent cannabis users (3–6), structural changes associated with marijuana use have not been consistent. Although some have reported decreases in regional brain volume such as in the hippocampus, orbitofrontal cortex, amygdala, and striatum (7–12), others have reported increases in amygdala, nucleus accumbens, and cerebellar volumes in chronic marijuana users (13–15). However, others have reported no observable difference in global or regional gray or white matter volumes in chronic marijuana users (16, 17). These inconsistencies could be attributed to methodological differences across studies pertaining to study samples (e.g., severity of marijuana use, age, sex, comorbidity with other substance use or psychiatric disorders) and/or study design (e.g., study modality, regions of interest).Because THC binds to cannabinoid 1 (CB1) receptors in the brain, when differences are observed, these morphological changes associated with marijuana use have been reported in CB1 receptor-enriched areas such as the orbitofrontal cortex, anterior cingulate, striatum, amygdala, insula, hippocampus, and cerebellum (2, 11, 13, 18). CB1 receptors are widely distributed in the neocortex, but more restricted in the hindbrain and the spinal cord (19). For example, in a recent study by Battistella et al. (18), they found significant brain volume reductions in the medial temporal cortex, temporal pole, parahippocampal gyrus, insula, and orbitofrontal cortex (OFC) in regular marijuana users compared with occasional users. Whether these reductions in brain volume lead to downstream changes in brain organization and function, however, is still unknown.Nevertheless, emergent studies have demonstrated a link between brain structure and connectivity. For example, Van den Heuvel et al. and Greicius et al. demonstrated robust structural connections between white matter indexes and functional connectivity strength within the default mode network (20, 21). Similarly, others have reported correlated patterns of gray matter structure and connectivity that are in many ways reflective of the underlying intrinsic networks (22). Thus, given the literature suggesting a direct relationship between structural and functional connectivity, it is likely that connectivity changes would also be present where alterations in brain volume are observed as a result of marijuana use.The goal of this study was to characterize alterations in brain morphometry and determine potential downstream effects in connectivity as a result of chronic marijuana use. To address the existing inconsistencies in the literature that may be in part due to methodological issues, we (i) used three different MRI techniques to investigate a large cohort of well-characterized chronic cannabis users with a wide age range (allowing for characterization without developmental or maturational biases) and compared them to age- and sex-matched nonusing controls; (ii) examined observable global (rather than select) gray matter differences between marijuana users and nonusing controls; and (iii) performed subsequent analyses to determine how these changes relate to functional and structural connectivity, as well as behavior. Given the existing literature on morphometric reductions associated with long-term marijuana use, we expected gray matter reductions in THC-enriched areas in chronic marijuana users that will be associated with changes in brain connectivity and marijuana-related behavior.     

Using functional magnetic resonance imaging to explore the possible mechanism of the action of acupuncture at Dazhong (KI 4) on the functional cerebral regions of healthy volunteers

Acupuncture at right Dazhong (KI 4) mostly affects functional magnetic resonance imaging signal in the right inferior frontal gyrus, right insular lobe, right thalamus, right middle frontal gyrus and right orbitofrontal cortex, which are associated with governing executive functions, emotional activities and social behaviour.     

Distinct contributions of the amygdala and parahippocampal gyrus to suspicion in a repeated bargaining game

Humans assess the credibility of information gained from others on a daily basis; this ongoing assessment is especially crucial for avoiding exploitation by others. We used a repeated, two-person bargaining game and a cognitive hierarchy model to test how subjects judge the information sent asymmetrically from one player to the other. The weight that they give to this information is the result of two distinct factors: their baseline suspicion given the situation and the suspicion generated by the other person's behavior. We hypothesized that human brains maintain an ongoing estimate of the credibility of the other player and sought to uncover neural correlates of this process. In the game, sellers were forced to infer the value of an object based on signals sent from a prospective buyer. We found that amygdala activity correlated with baseline suspicion, whereas activations in bilateral parahippocampus correlated with trial-by-trial uncertainty induced by the buyer's sequence of suggestions. In addition, the less credible buyers that appeared, the more sensitive parahippocampal activation was to trial-by-trial uncertainty. Although both of these neural structures have previously been implicated in trustworthiness judgments, these results suggest that they have distinct and separable roles that correspond to their theorized roles in learning and memory.     

Expression of adhesion molecules on acute leukemic blast cells and sensitivity to normal LAK activity

Summary Antigenic expression of CD54 and CD58 adhesion molecules was investigated on leukemic blast samples from ten patients with acute lymphoblastic (ALL) and 14 with acute myeloblastic (AML) leukemia. The mean intensity of fluorescence (MIF) was calculated and correlated with sensitivity of blast cells to the lytic activity of allogeneic lymphokine-activated killer (LAK) cells. CD54 antigen was expressed in all AML cases with an MIF of 11.2 while in ALL, though present in the majority of cases, it was absent in one case and expressed in less than 30% of blasts in two others, with an overall MIF of 3.0. CD58 expression was similar in both groups of patients, with an MIF of 7.6 in ALL and 7.0 in AML. In addition, in six of the ten ALL cases and in two of the 14 AML cases, leukemic blasts proved to be resistant to the cytotoxic activity of normal allogeneic LAK effectors. In these LAK-resistant patients, the CD54 antigenic expression was lower (p=0.03) than in LAK-sensitive patients with an MIF of 1.7 vs 4.9 in ALL and 1.35 vs 12.9 in AML cases. Finally, blocking of CD54 and/or CD58 receptors on leukemic blasts resulted in a slight reduction of⁵¹Cr release. Findings suggest that CD54 is differently expressed on myeloid and lymphoid blasts and that there is a correlation between CD54 MIF and susceptibility of blasts to the LAK activity.     

SARS病毒核酸检测中不同引物对灵敏度的影响

目的筛选灵敏、特异的SARS病毒核酸检测方法。方法采用世界卫生组织(WHO)和中国疾病预防控制中心(中国CDC)推荐的9对SARS病毒核酸检测引物，同时又选择市售的2种SARS荧光定量PCR试剂，分别对不同稀释度的SARS病毒核酸进行RT—PCR、巢式PCR和荧光定量PCR扩增，比较其检测灵敏度和特异性。结果两种荧光定量PCR试剂可检测SARS病毒核酸灵敏度均为0．1TCID50，与普通RT—PCR方法检测灵敏度(0.1TCID50)相同，而较巢式PCR法(0．01TCID50)略低；采用RT—PCR方法扩增SARS核酸时，以WHO推荐的SAR1s／SAR1as、BNIinS／BNIAs、BNIoutS/BnoutAs与中国CDC推荐的CDC-P1 ／P1-灵敏度最高。结论RT—PCR扩增时各引物对之间存在明显差异；荧光定量PCR可作为SARS疑似样本检测的首选方法，必要时再采用RT—PCR和巢式PCR法加以确认。