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At least 289 records · Page 16Linked to original sources
PubMed1999

The human antibody response to porcine xenoantigens is encoded by IGHV3-11 and IGHV3-74 IgVH germline progenitors.

Preformed and induced Ab responses present a major immunological barrier to the use of pig organs for human xenotransplantation. We generated IgM and IgG gene libraries established from lymphocytes of patients treated with a bioartificial liver (BAL) containing pig hepatocytes and used these libraries to identify IgVH genes that encode human Ab responses to pig xenoantigens. Genes encoded by the VH3 family are increased in expression in patients following BAL treatment. cDNA libraries representing the VH3 gene family were generated, and the relative frequency of expression of genes used to encode the Ab response was determined at days 0, 10, and 21. Ig genes derived from the IGHV3-11 and IGHV3-74 germline progenitors increase in frequency post-BAL. The IGHV3-11 gene encodes 12% of VH3 cDNA clones expressed as IgM Abs at day 0 and 32.4-39.0% of cDNA clones encoding IgM Abs in two patients at day 10. IGHV3-11 and IGHV3-74 genes encoding IgM Abs in these patients are expressed without evidence of somatic mutation. By day 21, an isotype switch occurs and IGHV3-11 IgVH progenitors encode IgG Abs that demonstrate somatic mutation. We cloned these genes into a phagemid vector, expressed these clones as single-chain Abs, and demonstrated that the IGHV3-11 gene encodes Abs with the ability to bind to the gal alpha (1,3) gal epitope. Our results demonstrate that the xenoantibody response in humans is encoded by IgVH genes restricted to IGHV3-11 and IGHV3-74 germline progenitors. IgM Abs are expressed in germline configuration and IgG Abs demonstrate somatic mutations by day 21.

Adult↗
PubMed1999

Medial temporal lobe activations in fMRI and PET studies of episodic encoding and retrieval.

Early neuroimaging studies often failed to obtain evidence of medial temporal lobe (MTL) activation during episodic encoding or retrieval, but a growing number of studies using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) have provided such evidence. We review data from fMRI studies that converge on the conclusion that posterior MTL is associated with episodic encoding; too few fMRI studies of retrieval have reported MTL activations to allow firm conclusions about their exact locations. We then turn to a recent meta-analysis of PET studies (Lepage et al., Hippocampus 1998;8:313-322) that appears to contradict the fMRI encoding data. Based on their analysis of the rostrocaudal distribution of activations reported during episodic encoding or retrieval, Lepage et al. (1998) concluded that anterior MTL is strongly associated with episodic encoding, whereas posterior MTL is strongly associated with episodic retrieval. After considering the evidence reviewed by Lepage et al. (1998) along with additional studies, we conclude that PET studies of encoding reveal both anterior and posterior MTL activations. These observations indicate that the contradiction between fMRI and PET studies of encoding was more apparent than real. However, PET studies have reported anterior MTL encoding activations more frequently than have fMRI studies. We consider possible sources of these differences.

Animals↗
PubMed1999

Medial temporal lobe activation during episodic encoding and retrieval: a PET study.

Recent neuroimaging studies have obtained evidence of activation in the medial temporal lobe (MTL) during episodic encoding and retrieval. On the basis of a meta-analysis of MTL activations in studies that used positron emission tomography (PET), Lepage et al. (Hippocampus 1998;8:313-322) suggested that episodic encoding tends to involve the anterior MTL, whereas episodic retrieval tends to involve the posterior MTL. In a meta-analysis of studies that used PET and functional magnetic resonance imaging, Schacter and Wagner (Hippocampus 1999;9:7-24) reported weaker evidence for such a rostrocaudal distribution of encoding and retrieval activations. However, these meta-analyses were based largely on studies that examined encoding or retrieval separately. Here, we report a direct, within-subjects comparison of MTL activation during episodic encoding and retrieval by using PET. Results indicated that both encoding and retrieval were associated with blood flow increases in similar MTL regions with little indication that encoding and retrieval are preferentially associated with activity in the anterior versus the posterior MTL. Direct comparisons revealed greater blood flow increases in posterior MTL during encoding than retrieval.

Adult↗
PubMed1999

Parametric fMRI analysis of visual encoding in the human medial temporal lobe.

A number of functional brain imaging studies indicate that the medial temporal lobe system is crucially involved in encoding new information into memory. However, most studies were based on differences in brain activity between encoding of familiar vs. novel stimuli. To further study the underlying cognitive processes, we applied a parametric design of encoding. Seven healthy subjects were instructed to encode complex color pictures into memory. Stimuli were presented in a parametric fashion at different rates, thus representing different loads of encoding. Functional magnetic resonance imaging (fMRI) was used to assess changes in brain activation. To determine the number of pictures successfully stored into memory, recognition scores were determined afterwards. During encoding, brain activation occurred in the medial temporal lobe, comparable to the results obtained by others. Increasing the encoding load resulted in an increase in the number of successfully stored items. This was reflected in a significant increase in brain activation in the left lingual gyrus, in the left and right parahippocampal gyrus, and in the right inferior frontal gyrus. This study shows that fMRI can detect changes in brain activation during variation of one aspect of higher cognitive tasks. Further, it strongly supports the notion that the human medial temporal lobe is involved in encoding novel visual information into memory.

Adult↗
PubMed1999

Improved three-dimensional GRASE imaging with the SORT phase-encoding strategy.

The phase-encoding strategy plays a critical role in determining the quality of gradient- and spin-echo (GRASE) images. Phase-encoding methods developed for two-dimensional GRASE imaging strive to achieve a balance between artifacts from T2-dependent signal amplitude modulations and off-resonance-dependent signal phase shifts, although no current method provides smooth and nonperiodic evolutions for both of these signal changes. In three-dimensional GRASE imaging, the use of two phase-encoding directions presents the opportunity for improved phase-encoding strategies. In this report a phase-encoding strategy for three-dimensional GRASE, termed SORT, is described; this strategy separates off-resonance and T2 effects, mapping one along each of the two phase-encoding directions. Thus, off-resonance-induced artifacts can be minimized while eliminating T2-dependent periodic signal modulations and allowing complete flexibility in the selection of echo time. The performance of the SORT phase-encoding method for T2-weighted GRASE imaging was compared with that of existing methods based on calculated point spread functions and simulated images. The predicted performance of SORT phase encoding was verified experimentally using T2-weighted three-dimensional GRASE imaging of the brain. Generally artifact-free images were obtained even in the presence of fat, susceptibility interfaces, and a wide range of T2 values.

Artifacts↗
PubMed2000

Conjunction analysis of cortical activations common to encoding and retrieval.

The notion of overlap between encoding and retrieval processes is central in cognitive theories of episodic memory, but to date most functional neuroimaging studies have emphasized differences between these processes. In the present study, overlap between encoding and retrieval processes was investigated by analyzing data from a positron emission tomography (PET) study of encoding and retrieval of different kinds of event information. Using a conjunction analysis, we specifically aimed at identifying overlap in activation patterns for encoding and retrieval of three classes of event information: item, temporal, and spatial. It was found that both encoding and retrieval of spatial information activated posterior parietal areas bilaterally. In addition, item encoding and retrieval were associated with increased activity in the right temporal pole, and temporal encoding and retrieval with left inferior frontal and left inferior temporal regions. These findings suggest that when specific episodic information is retrieved from memory, regions involved in encoding of the same information are engaged.

Brain Mapping↗
PubMed1994

The rat, mouse and human genes encoding the receptor for parathyroid hormone and parathyroid hormone-related peptide are highly homologous.

The organization of the PTH/PTHrP receptor gene is highly homologous in three mammalian species, rat, human and mouse. This gene extends over 22 kb and contains at least 15 exons and 14 introns. The most 5' exon we have identified (exon U) is followed by an approximately 1kb intron. The second exon (exon S) encodes the initiator methionine and the putative signal peptide and is followed by the largest intron of this gene (about 11 kb). The amino-terminal extracellular region is encoded by 4 exons (E1, E2, E3 and G); exon G contains all 4 potential glycosylation sites. Membrane-spanning domains 1-4 and portions of their connecting intracellular and extracellular loops are encoded by 4 exons (M1, M2, M3 and M4). The second extracellular loop and portions of 4th and 5th membrane-spanning domains are encoded by one exon, EL2. The 5th membrane-spanning domain and portion of the 3rd intracellular loop are encoded by one exon, M5. The 6th membrane-spanning domain, the 3rd extracellular loop and the proximal part of the 7th membrane-spanning domain are encoded by one single exon (M6/7); the remaining sequence of the 7th membrane-spanning domain is encoded by a short exon, M7. The carboxy-terminal tail of the receptor and the 3' untranslated region are encoded by one single exon, exon T. The 3' untranslated region does not contain the classical polyadenylation signal, AATAAA. Expression in COS-7 cells of a minigene constructed of a 5' rat cDNA fragment (1.3 Kb) ligated in-frame to a 3' genomic fragment at the NsiI site, which is located in exon M6/7 resulted in a transcript that was translated into a functional receptor; it bound PTH and showed PTH-stimulated accumulation of intracellular cAMP. Therefore, the PTH/PTHrP receptor gene contains alternative 3' sequences that allow cleavage and polyadenylation of its transcript.

Animals↗
PubMed1996

Improving clinician's coded data entry through the use of an electronic patient record system: 3.5 years experience with a semiautomatic browsing and encoding tool in clinical routine.

This report presents data on clinicians' use of a browsing and encoding utility. Traditional and computerized discharge summaries during three phases of coding ICD-9 diagnoses were compared: phase I (no coding), phase II (manual coding), and phase III (computerized semiautomatic coding). Our data indicate that only 50% of all diagnoses in a discharge summary are encoded manually; using a computerized browsing and encoding utility this rate may increase by 64%; when forced to encode diagnoses manually users may "shift" as much as 84% of relevant diagnoses from the appropriate section to other sections, thereby "bypassing" the need to encode. This effect can be partially reversed by up to 41% with the computerized approach. Using a computerized encoding help can ensure completeness of encoding data (from 46 to 100%). We conclude that the use of a computerized browsing and encoding tool by clinicians can increase data quality and the volume of documented data. Mechanisms bypassing the need to code can be reversed.

Diagnosis↗
PubMed2001

An examination of the effects of stimulus type, encoding task, and functional connectivity on the role of right prefrontal cortex in recognition memory.

Right anterior prefrontal cortex and other brain areas are active during memory retrieval but the role of prefrontal cortex and how it interacts with these other regions to mediate memory function remain unclear. To explore these issues we used positron emission tomography to examine the effects of stimulus material and encoding task on brain activity during visual recognition, assessing both task-related changes and functional connectivity. Words and pictures of objects were encoded using perceptual and semantic strategies, resulting in better memory for semantically encoded items. There was no significant effect of prior encoding strategy on brain activity during recognition. Right anterior prefrontal cortex was equally active during recognition of both types of stimuli irrespective of initial encoding strategy. Regions whose activity was positively correlated with activity in right anterior prefrontal cortex included widespread areas of prefrontal and inferior temporal cortices bilaterally. Activity in this entire network of regions was negatively correlated with recognition accuracy of semantically encoded items. These results suggest that initial encoding task has little impact on the set of brain regions that is active during subsequent recognition. Right anterior prefrontal cortex appears to be involved in retrieval mode, reflected in its equivalent activity across conditions differing in both stimulus type and encoding task, and also in retrieval effort, shown by the negative correlation between its functional connectivity and individual differences in recognition accuracy.

Adult↗
PubMed2000

Antitumor efficacy of tumor-antigen-encoding recombinant poxvirus immunization in Dunning rat prostate cancer: implications for clinical genetic vaccine development.

One potential use for prostate-cancer-associated genes discovered through ongoing genetics studies entails the construction of virus- or plasmid-based recombinant vector vaccines encoding these new tumor-associated antigens (TAA) to induce TAA-specific immune responses for the prevention or therapy of prostate cancer. Clinical trials evaluating prototypes of such recombinant vaccines are under way. TAA-encoding recombinant vector vaccines, however, have not previously been evaluated in a prostate-cancer animal model. For assessment of the potential susceptibility of prostate cancer to genetic immunization strategies using TAA-encoding recombinant vectors, the antitumor efficacy of a model recombinant viral vector encoding a TAA was evaluated in rat Dunning prostate cancer. Recombinant vaccinia was chosen as a prototype virus vector encoding a TAA for these studies, and beta-galactosidase was chosen as a model target TAA. Dunning AT-2 cells were transduced with a retroviral vector to express beta-galactosidase, and the susceptibility of tumorigenic AT-2-lacZ cells to immunization with vaccinia-lacZ was measured using protection studies in Copenhagen and nu/nu rats. Stably transduced AT-2-lacZ cells expressing beta-galactosidase as measured by enzymatic substrate-based assays were found to retain their tumorigenicity in vivo despite abundant expression of rat major histocompatibility complex (MHC) class I. Immunization with model TAA-encoding recombinant vaccinia-lacZ conferred significant protection against subsequent growth of AT-2-lacZ cells in vivo (P = 0.01); however, the efficacy of such immunization was markedly dependent on the volume of tumor challenge. The antitumor efficacy of TAA-encoding recombinant vaccinia immunization was abrogated in nu/nu rats, suggesting a T-cell-dependent mechanism of activity. These studies suggest that prostate cancer may be a suitable target for immunization strategies using TAA-encoding recombinant vectors. Such immunization strategies may be more effective in settings of minimal cancer burden.

Animals↗
PubMed1996

A numerical simulation of muscle spindle ensemble encoding during planar movement of the human arm: correlation sensitivity and parameter dependence.

We extend the analysis developed in the preceding paper in which we correlated kinematic parameters of planar movements of the human arm made by subjects moving to a visual target with numerical estimates of the ensemble encoding of muscle spindles within some of the muscles of this limb. Three possible models for the inclusion of noise in the calculations of the ensemble encodings are considered: (i) random errors in the angular coordinates from which muscle fascicle, and hence spindle length are calculated, (ii) variability of spindle discharge rates, and (iii) variability in the calculation of the ensemble encoding. In each case the correlations between kinematic variables of the movements and the resultant ensemble encodings decrease as the contribution of the noise term to the calculation of the encodings increases. Subject to the constraint that the magnitude of the noise term remains within physiologically realistic limits, however, the observed correlations persist at statistically significant levels. We also investigate the dependence of the observed correlations on the choice of model parameters, namely (i) the absolute and relative contributions made by simulated spindle primary and secondary afferents to the ensemble encoding, (ii) the inclusion of explicit length-related terms in the model of muscle spindle discharge, and (iii) the fractional power of velocity experienced by the model spindles during movement. The resulting correlations are approximately independent of both the fractional power of velocity and absolute firing levels of both the primary and secondary afferents of the spindle model. The inclusion of explicit length-dependent terms in the model does result in differences in the observed correlation coefficients. In this case, however, the magnitudes of the differences are small. On the basis of these findings we conclude that the correlations between kinematic variables of movement and the associated ensemble encodings are robust with regard to both the choice of model parameters and noise inherent at all stages of the transduction and processing of proprioceptive information. The findings of the present study provide further evidence, therefore, to support the hypothesis that motor structures capable of deriving such an ensemble encoding would be provided with information regarding ongoing movements in both intrinsic (body-centered) and extrinsic (Cartesian) coordinate systems.

Animals↗
PubMed1987

Dual task performance in children: generalized and lateralized effects of memory encoding upon the rate and variability of concurrent finger tapping.

Interference between concurrent tasks was used to investigate the brain basis of capacity limitations apparent when children encode information. Seventy-three right-handed children in Grades 1-4 engaged in speeded unilateral finger tapping while encoding a variable number of faces or numbers for subsequent recognition testing. With both face and number encoding, tapping rate decreased as memory load increased. Encoding numbers was more disruptive than encoding faces. Both encoding tasks slowed right-hand tapping more than left-hand tapping, relative to control tapping performance, but had only a bilateral effect on the variability of tapping. Although overall interference was less than that observed with a comparison task (i.e., speaking), the asymmetry of interference was comparable. The results suggest that cerebral lateralization for memory encoding, as well as for speech, is constant across the age range of 6-10 years. Findings regarding developmental change in overall capacity, however, are task specific: interference from speaking but not from memory encoding decreases with increasing age.

Attention↗
PubMed2005

Effect of tobacco craving cues on memory encoding and retrieval in smokers.

Previous studies have shown that cue-elicited tobacco craving disrupted performance on cognitive tasks; however, no study has examined directly the effect of cue-elicited craving on memory encoding and retrieval. A distinction between encoding and retireval has been reported such that memory is more impaired when attention is divided at encoding than at retrieval. This study tested the hypothesis that active imagery of smoking situations would impair encoding processes, but have little effect on retrieval. Imagery scripts (cigarette craving and neutral content) were presented either before presentation of a word list (encoding trials) or before word recall (retrieval trials). A working memory task at encoding and free recall of words were assessed. Results indicated that active imagery disrupted working memory on encoding trials, but not on retrieval trials. There was a trend toward impaired working memory following craving scripts compared with neutral scripts. These data support the hypothesis that the cognitive underpinnings of encoding and retrieval processes are distinct.

Adolescent↗
PubMed2005

Is nuclear respiratory factor 2 a master transcriptional coordinator for all ten nuclear-encoded cytochrome c oxidase subunits in neurons?

Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial electron transport chain, is a multi-subunit, bigenomically encoded inner mitochondrial membrane protein. Of the thirteen subunits, three are encoded in the mitochondrial genome and ten others are encoded in the nuclear genome. Transcriptional coordination of nuclear-encoded COX subunit genes is likely accomplished by transcription factors responding to upstream signals. Previous studies have found that nuclear-encoded COX subunit genes are under the control of specific transcription factors, such as nuclear respiratory factor 2 (NRF-2). However, it is not known if a single transcription factor binds to all ten of COX subunit promoters. In the current study, we identified in silico putative NRF-2 binding sites on all ten nuclear-encoded COX gene promoters in the rat genome. Chromatin immunoprecipitation assay showed that NRF-2 bound in vivo to six of the ten nuclear-encoded COX subunit promoters. Electrophoretic mobility supershift assays demonstrated binding of NRF-2 to the other four subunits, and promoter mutation study confirmed the functionality of these NRF-2 binding sites. Finally, transfection of dominant-negative constructs of NRF-2 proteins caused a significant reduction of COX expression. We conclude that NRF-2 is an important mediator of coordinated regulation of all ten nuclear-encoded COX subunit genes in neurons.

Animals↗
PubMed2006

The Drosophila melanogaster DmCK2beta transcription unit encodes for functionally non-redundant protein isoforms.

Genes encoding for the two evolutionary highly conserved subunits of a heterotetrameric protein kinase CK2 holoenzyme are present in all examined eukaryotic genomes. Depending on the organism, multiple transcription units encoding for a catalytically active CK2alpha subunit and/or a regulatory CK2beta subunit may exist. The phosphotransferase activity of members of the protein kinase CK2alpha family is thought to be independent of second messengers but is modulated by interaction with CK2beta-like proteins. In the genome of Drosophila melanogaster, one gene encoding for a CK2alpha subunit and three genes encoding for CK2beta-like proteins are present. The X-linked DmCK2beta transcription unit encodes for several CK2beta protein isoforms due to alternative splicing of its primary transcript. We addressed the question whether CK2beta-like proteins are redundant in function. Our in vivo experiments show that variations of the very C-terminal tail of CK2beta isoforms encoded by the X-linked DmCK2beta transcription unit influence their functional properties. In addition, we find that CK2beta-like proteins encoded by the autosomal D. melanogaster genes CK2betates and CK2beta' cannot fully substitute for a loss of CK2beta isoforms encoded by DmCK2beta.

Alleles↗
PubMed2006

Prefrontal and hippocampal contributions to the generation and binding of semantic associations during successful encoding.

The ability to form and bind associations between items is an important aspect of successful memory formation. We hypothesize that, during encoding, the left inferior frontal gyrus (IFG) supports generation of associations between items and the hippocampus then binds these associations. This study examined the parametric responses of these regions to varying amounts of generative and relational processing during successful encoding (i.e., for subsequently recognized items). Encoding involved presentation of word triads varying in the number of semantic associations among them (none, one or all); participants judged how many associations were present in each triad. Thus, triads with fewer associations had higher generative load while triads with more associations had higher relational load. Participants later completed a forced-choice recognition test for encoding triads. Successful encoding relative to a control task resulted in activation of bilateral IFG and left hippocampus, and the hippocampus also exhibited a significant subsequent memory effect (hits>misses). Linear parametric analyses revealed that generative load modulated activity in bilateral IFG while relational load correlated with activity in left hippocampus. Although univariate analyses distinguished IFG and hippocampal contributions to the generative and relational stages of encoding, respectively, effective connectivity between these regions did not differ according to condition. Furthermore, this analysis revealed that the left IFG played a pivotal role in coordinating associative encoding processes. Our findings illustrate that modulation of components in a memory network can be independent of patterns of mutual connectivity among those components in mediating successful encoding.

Adult↗
PubMedDate not supplied

Regional brain activations predicting subsequent memory success: an event-related fMRI study of the influence of encoding tasks.

We determined the brain regions that were differentially sensitive to two, randomly inter-mixed tasks: Deep Encoding, in which subjects processed items according to their meaning (is the word pleasant or unpleasant?) and Shallow Encoding, in which items were processed according to two underlined letters in the word (are the letters in alphabetical order?). The former task was associated with activations in a set of brain regions including left lateral prefrontal cortex (PFC) and left medial temporal cortex. The latter showed relatively greater activation in right PFC. Both findings are consistent with predictions made on the basis of previous functional neuroimaging work. Following scanning, each subject underwent a recognition memory task. The results of these provided the basis for a further sub-division of encoding events, according to whether they were predictive of subsequent recognition success or not. Unsurprisingly, recognition performance was greater for words that had been deeply encoded. For both encoding conditions, words that were subsequently recognised were associated with greater activation in a sub-set of regions identified by the deep versus shallow contrast. These included left PFC and medial temporal regions. In left PFC this performance-predicting activation was significantly greater for the deep encoding condition. Our results support previous studies suggesting a role for left PFC and medial temporal cortex in episodic memory encoding. They provide more evidence, too, for a less consistent finding: the interaction between the encoding task and the success of subsequent recognition.

Adult↗
PubMed1989

Developmental studies of alertness and encoding effects of stimulus repetition.

The findings reviewed here suggest a broadened view of the stimulus-familiarization effect as one of a general class of phenomena resulting from repetition-induced changes in the processes of alterness and encoding. Cantor's original observation of slowed responding to familiarized stimuli can be attributed on this account to experimental conditions under which the magnitude of alterness decrement is greater than encoding facilitation. Exactly the opposite result can be obtained by arranging conditions so as to highlight the encoding facilitation effect relative to the alterness decrement effect. For example, faster responding to familiarized stimuli has been found under conditions in which (1) the imperative stimulus is preceded by a neutral warning signal or, (2) a delay is imposed between the familiarization and the test phases. Earlier, it was noted that the experimental technique of repeated stimulus presentation is widely used in the study of infant perception, with little concern for the mechanisms responsible for what is generically referred to as habituation. Posner and Rothbart (1980) made a similar observation and suggested, on the basis of Kraut's (1976) results, that Habituation in the infant can be viewed as a reduction in the flow of information from the recognition pathway [encoding] into the alerting system. Input is still processed along the recognition pathway, but its failure to activate the alerting system reduces the availability of the central processor and hence of nonhabitual responses. We have developed a model of attention that accounts for our findings and embodies Posner and Rothbart's general idea. It suggests that both the alertness and the encoding functions must reach separate threshold levels for a correct recognition response. The time required to get to each threshold level is changed as a function of stimulus repetition. Repetition slows alertness "rise time," but it speeds encoding "rise time." In comparing the responses to a familiarized color versus those to a novel color, the model can be seen in Fig. 1a. Because any response must await an appropriate level of alertness, the familiarized stimulus is responded to more slowly than the novel one, even though encoding rise time to the familiarized stimulus if fast. Either a delay between familiarization and test or a warning signal acts to mitigate the effects of familiarization on alertness. Alertness rise time for the familiarized stimulus is similar to that for the novel stimulus, but encoding rise time for the familiarized stimulus is faster than for the novel.(ABSTRACT TRUNCATED AT 400 WORDS)

Arousal↗