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At least 739 records · Page 41Linked to original sources
PubMed2006

Acute tryptophan depletion reduces activation in the right hippocampus during encoding in an episodic memory task.

Acute tryptophan depletion (ATD), a well-recognized method to lower central serotonin levels, was used to examine the effects of lower central serotonin levels on memory function in healthy males. Functional Magnetic Resonance Imaging (fMRI) was used to examine changes in brain activation during the encoding and the retrieval phase of a visual verbal episodic memory task. ATD led to more positively rated words in the encoding phase and to poorer recognition of these positively rated words in the retrieval phase. Furthermore, encoding was accompanied by enhanced brain activation in occipital, middle and superior frontal, anterior and posterior cingulate and striatal areas. Retrieval attempt was accompanied by enhanced activation in the cuneus, inferior occipital gyrus and inferior and middle frontal areas. Retrieval success was accompanied by activation in an extensive network including frontal, parietal, temporal, cingulate, striatal and cerebellar areas. In the encoding phase ATD attenuated activation in the right hippocampus and ATD did not affect brain activity in the retrieval phase. These results show that serotonin is important in long term memory processes, and that serotonin acts on the encoding phase and not on the retrieval phase.

Adult↗
PubMed2006

Performance on an episodic encoding task yields further insight into functional brain development.

To further characterize changes in functional brain development that are associated with the emergence of cognitive control, participants 14 to 28 years of age were scanned while performing an episodic encoding task with a levels-of-processing manipulation. Using data from the 12 youngest and oldest participants (endpoint groups), 18 regions were identified that showed group differences in task-related activity as a function of processing depth. One region, located in left inferior frontal gyrus, showed enhanced activity in deep relative to shallow encoding that was larger in magnitude for the older group. Seventeen regions showed enhanced activity in shallow relative to deep encoding that was larger in magnitude for the youngest group. These regions were distributed across a broad network that included both cortical and subcortical areas. Regression analyses using the entire sample showed that age made a significant contribution to the difference in beta weights between deep and shallow encoding for 17 of the 18 identified regions in the direction predicted by the endpoint analysis. We conclude that the patterns of brain activation associated with deep and shallow encoding differ between adolescents and young adults in a manner that is consistent with the interactive specialization account of functional brain development.

Adolescent↗
PubMed2005

Virus-encoded chemokine receptors--putative novel antiviral drug targets.

Large DNA viruses, in particular herpes- and poxviruses, have evolved proteins that serve as mimics or decoys for endogenous proteins in the host. The chemokines and their receptors serve key functions in both innate and adaptive immunity through control of leukocyte trafficking, and have as such a paramount role in the antiviral immune responses. It is therefore not surprising that viruses have found ways to exploit and subvert the chemokine system by means of molecular mimicry. By ancient acts of molecular piracy and by induction and suppression of endogenous genes, viruses have utilized chemokines and their receptors to serve a variety of roles in viral life-cycle. This review focuses on the pharmacology of virus-encoded chemokine receptors, yet also the family of virus-encoded chemokines and chemokine-binding proteins will be touched upon. Key properties of the virus-encoded receptors, compared to their closest endogenous homologs, are interactions with a wider range of chemokines, which can act as agonists, antagonists and inverse agonists, and the exploitation of many signal transduction pathways. High constitutive activity is another key property of some--but not all--of these receptors. The chemokine receptors belong to the superfamily of G-protein coupled 7TM receptors that per se are excellent drug targets. At present, non-peptide antagonists have been developed against many chemokine receptors. The potentials of the virus-encoded chemokine receptors as drug targets--ie. as novel antiviral strategies--will be highlighted here together with the potentials of the virus-encoded chemokines and chemokine-binding proteins as novel anti-inflammatory biopharmaceutical strategies.

Animals↗
PubMed2005

Contributions of occipital, parietal and parahippocampal cortex to encoding of object-location associations.

Events are stored in our episodic memory in varying degrees of accessibility for conscious retrieval and combined with varying amounts of associated information. A crucial aspect of episodic memory is to bind information together, e.g. linking an object to a certain location. Spontaneous or experimenter-induced variance in the allocation of attentional resources during encoding critically determines the strength of the resulting memory trace especially for associative information as measured in subsequent memory tests. The neural correlates of associative memory encoding were investigated by lesion, PET- and fMRI-studies. So far no study aimed to assess the memory for associative information in a non-categorical way. Such a parametric assessment opens the possibility for a closer inspection of the relationship between brain activity and memory trace formation. We established a novel associative object-location memory paradigm, together with a parametric assessment of subsequent memory performance for spatial location which allows: (i) to determine if associative information is retrieved in a continuous or discontinuous manner during recognition and (ii) to investigate the relationship between activity during encoding and the resulting memory trace. Such correlations were observed in the occipital, parietal and the parahippocampal cortex, areas known to be involved in processing either objects and/or locations. The analysis of response functions revealed for the majority of areas involved in encoding a continuous relationship between brain activity during encoding and the confidence in a subsequent memory test.

Adult↗
PubMed2006

Self-awareness and the subconscious effect of personal pronouns on word encoding: a magnetoencephalography (MEG) study.

The effect of personal pronouns such as "ein" (German for "a"), "mein" (German for "my") and "sein" (German for "his") on the processing of associated nouns was investigated using MEG. Three different encoding strategies were provided in order to vary the level of consciousness involved in verbal information processing. A shallow (alphabetic), a deep (semantic) and a very deep (contextual) encoding instruction related to visual word presentation were given to all study participants. After the encoding of pronoun-noun pairs, recognition performances of nouns only were tested. The number of correctly recognized nouns previously associated with "sein" was significantly lower than the number of correctly recognized nouns previously associated with "ein" in the shallow encoding condition. The same trend was found for "mein" associated nouns which were also less accurately recognized compared to "ein" associated nouns. Magnetic field distributions recorded during the encoding phases revealed two significant effects, one between about 200 and 400ms after stimulus onset and the other between about 500 and 800ms. The earlier effect was found over occipito-parietal sensors, whereas the later effect occurred over left frontal sensors. Within both time ranges, brain activation varied significantly as a function of associated pronoun independent of depth of word processing. In the respective areas of both time ranges, conditions including personal pronouns ("mein" and "sein") showed higher magnetic field components compared to the control condition of no personal pronouns ("ein"). Evidence is shown that early stage processing is able to distinguish between no personal and personal information, whereas later stage processing is able to distinguish between information related to oneself and to another person (self and non-self). Along with other previous reports our MEG findings support the notion that particular human brain functions involved in processing neurophysiological correlates of self and non-self can be identified.

Adult↗
PubMed2004

Plasmids encoding membrane-bound IL-4 or IL-12 strongly costimulate DNA vaccination against carcinoembryonic antigen (CEA).

Vaccination with plasmids encoding an antigen of interest (DNA vaccination) is a new strategy to achieve effective immunization against many agents. DNA vaccination can be ameliorated by co-administration of plasmids encoding a cytokine. Thus far, only plasmids encoding soluble cytokines have been used for this purpose. However, these plasmids can induce release of cytokines into the circulation and could potentially cause many undesirable effects. We undertook this study to determine whether membrane-bound cytokines, which would restrict their localization at the site of administration, can act as immunoadjuvants. We and others have previously shown that plasmids encoding soluble IL-4 and IL-12 are effective adjuvants for DNA vaccination. In this study, we demonstrate that DNA co-vaccination with membrane-bound IL-4 (mbIL-4) or membrane-bound IL-12 (mbIL-12) both enhance anti-CEA immunity, as detected by in vitro and in vivo assays. Mice co-injected with plasmids encoding CEA and either type of membrane-bound cytokine rejected transplanted CEA-positive tumor cells strongly. Notably, unlike secreted IL-4, mbIL-4 was the most effective adjuvant for anti-tumor immunity. This study demonstrates that membrane-bound cytokines are suitable adjuvants for DNA vaccination.

Adjuvants, Immunologic↗
PubMed2005

Real-time RT-PCR quantification of mRNA encoding cytokines and chemokines in histologically normal canine nasal, bronchial and pulmonary tissue.

Cytokines and chemokines are likely to be involved in the pathogenesis of inflammatory diseases of the canine respiratory tract. The roles and relative amounts of these molecules have not yet been defined in the respiratory mucosa of normal dogs or dogs with naturally acquired respiratory inflammation. In the present study, real-time reverse transcriptase polymerase chain reaction (RT-PCR) assays were employed to quantify messenger RNA (mRNA) encoding the chemokines monocyte chemotactic protein (MCP)-2, eotaxin-2 and eotaxin-3, and the cytokines interleukin-4 (IL-4), IL-5, IL-6, IL-10, IL-12p40, IL-18, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) in normal nasal, bronchial and pulmonary tissues from puppies (n = 4) and from adult dogs (n = 7). There was no significant difference in the expression of any transcript between puppies and adult dogs at any of the anatomical sites examined. The expression of mRNA encoding eotaxin-2 and eotaxin-3 increased significantly with progression from the nasal mucosa to pulmonary parenchyma but expression of MCP-2 mRNA did not show this trend. At all levels of the respiratory mucosa, the most abundant transcripts were those encoding IL-18 and TGF-beta. Transcripts encoding IL-6, IL-10, IL-12 and TNF-alpha were approximately ten-fold less abundant, and IL-4, IL-5 and IFN-gamma were the least abundant templates. There was significantly different amount of mRNA encoding IL-5, IL-18 and TNF-alpha between particular anatomical levels of the respiratory mucosa while the mRNA expression of the other cytokines was similar at all anatomical sites. The results of the present study will enable comparisons to be made with results obtained from similar samples obtained from dogs with nasal, bronchial or pulmonary diseases.

Age Factors↗
PubMed1998

Using encoding and retrieval strategies to improve 24-hour dietary recalls among older adults.

OBJECTIVE: To examine whether using an encoding strategy and/or providing more support at the time of retrieval improves the accuracy of 24-hour dietary recalls among the elderly. DESIGN: Posttest-only control group design. SETTING: The sample was recruited through advertisements and at senior centers and a low-income apartment building in rural central Pennsylvania. SUBJECTS: Study participants were 21 men and 73 women aged 58 years old and older. Everyone completed the study. INTERVENTION: The treatment group was unobtrusively guided in use of an encoding strategy before consuming the prepared meal. MAIN OUTCOME MEASURES: A 24-hour dietary recall and recognition tests were administered the next day for the foods consumed at the meal and for serving sizes of 5 of the foods. Memory tests were also administered. STATISTICAL ANALYSES PERFORMED: Linear regression was used to examine differences between the treatment and control groups and to identify variables that explained variation in the number of foods correctly recalled or recognized. The Chi 2 test was used to examine correct vs incorrect recall or recognition of the serving sizes of the 5 foods between the groups and to identify explanatory variables for this task. RESULTS: Subjects remembered more foods when they used an encoding strategy and when recognition replaced free recall; they performed best when both strategies were used. Use of this encoding strategy did not improve accurate recall or recognition of serving sizes of 5 foods; however, performances did improve when recognition replaced free recall. CONCLUSIONS: Among older adults, use of an encoding strategy and provision of support at the time of retrieval enhances memory of foods consumed but not of amounts consumed. To strengthen memory of foods consumed, older adults need to perform effortful memory tasks when they are eating.

Aged↗
PubMed1998

Pitch vs. spectral encoding of harmonic complex tones in primary auditory cortex of the awake monkey.

Neuromagnetic studies in humans and single-unit studies in monkeys have provided conflicting views regarding the role of primary auditory cortex (A1) in pitch encoding. While the former support a topographic organization based on the pitch of complex tones, single-unit studies support the classical tonotopic organization of A1 defined by the spectral composition of the stimulus. It is unclear whether the incongruity of these findings is due to limitations of noninvasive recordings or whether the discrepancy genuinely reflects pitch representation based on population encoding. To bridge these experimental approaches, we examined neuronal ensemble responses in A1 of the awake monkey using auditory evoked potential (AEP), multiple-unit activity (MUA) and current source density (CSD) techniques. Macaque monkeys can perceive the missing fundamental of harmonic complex tones and therefore serve as suitable animal models for studying neural encoding of pitch. Pure tones and harmonic complex tones missing the fundamental frequency (f0) were presented at 60 dB SPL to the ear contralateral to the hemisphere from which recordings were obtained. Laminar response profiles in A1 reflected the spectral content rather than the pitch (missing f0) of the compound stimuli. These findings are consistent with single-unit data and indicate that the cochleotopic organization is preserved at the level of A1. Thus, it appears that pitch encoding of multi-component sounds is more complex than suggested by noninvasive studies, which are based on the assumption of a single dipole generator within the superior temporal gyrus. These results support a pattern recognition mechanism of pitch encoding based on a topographic representation of stimulus spectral composition at the level of A1.

Acoustic Stimulation↗
PubMed2003

Reverse transcriptase and reverse splicing activities encoded by the mobile group II intron cobI1 of fission yeast mitochondrial DNA.

Mobile group II introns encode multidomain proteins with maturase activity involved in splicing and reverse transcriptase (RT) and (often) endonuclease activities involved in intron mobility. These activities are present in a ribonucleoprotein complex that contains the excised intron RNA and the intron-encoded protein. Here, we report biochemical studies of the protein encoded by the group IIA1 intron in the cob gene of fission yeast Schizosaccharomyces pombe mitochondria (cobI1). RNP particle fractions from the wild-type fission yeast strain with cobI1 in its mtDNA have RT activity even without adding an exogenous primer. Characterization of the cDNA products of such reactions showed a strong preference for excised intron RNA as template. Two main regions for initiation of cDNA synthesis were mapped within the intron, one near the DIVa putative high-affinity binding site for the intron-encoded protein and the other near domain VI. Adding exogenous primers complementary to cob exon 2 sequences near the intron/exon boundary stimulated RT activity but mainly for pre-mRNA rather than mRNA templates. Further in vitro experiments demonstrated that cobI1 RNA in RNP particle fractions can reverse splice into double-stranded DNA substrates containing the intron homing site. Target DNA primed reverse transcription was not detected unless a DNA target was used that was already nicked in the antisense strand of exon 2. This study shows that S.pombe cobI1 encodes RNP particles that have most of the biochemical activities needed for it to be a retroelement. Interestingly, it appears to lack an endonuclease activity, suggesting that the active homing exhibited by this intron in crosses may differ somewhat from that of the better-characterized introns.

Blotting, Northern↗
PubMedDate not supplied

Memory and schizophrenia: differential link of processing speed and selective attention with two levels of encoding.

The purpose of this study was to investigate how underlying cognitive deficits such as a defect in processing speed or in selective attention contributed to different types of memory impairment observed in schizophrenia (superficial vs deep encoding). 49 schizophrenic patients and 40 normal controls were administered a verbal memory task. Superficial encoding was assessed by the ability to recall items in their serial order. Deep encoding was assessed by the ability to organise words into semantic categories. Two measures of processing speed (Digit Symbol Substitution Test and Stroop colour time) and one measure of selective attention (Stroop test) were used. Regression analyses were carried out. In the patient group, processing speed contributed to both superficial and deep encoding, and to a global verbal memory score. Selective attention only contributed to the superficial encoding processes. Thus, slowing of processing speed in schizophrenia seems to be more crucial for memory performance, since it affects memory in a pervasive way.

Adult↗
PubMed2003

Adenovirus encoding soluble tumor necrosis factor alpha receptor immunoglobulin prolongs gene expression of a cotransfected reporter gene in rat lung.

OBJECTIVE: Because almost all pulmonary diseases are not caused by one gene, multiple gene transfection is required for current gene therapy. Adenovirus is an important gene therapy vector, but a short duration and the inability of repeated administration remain limitations. The aims of this study were to evaluate whether adenoviral vector encoding soluble tumor necrosis factor alpha receptor immunoglobulin and beta-galactosidase cotransfection prolongs gene expression and facilitates repeated vector administration to investigate the feasibility of a cotransfection strategy. METHODS: F344 rats received intratracheal administration of 1 x 10(9) plaque-forming units of adenoviral vector encoding beta-galactosidase or both adenoviral vector encoding beta-galactosidase and adenoviral vector encoding soluble tumor necrosis factor alpha receptor immunoglobulin. In the expression study beta-galactosidase gene expression in the lung was examined by means of enzyme-linked immunosorbent assay on days 2, 7, 14, 28, and 56 (n = 4/day). In the repeated transfection study, soluble tumor necrosis factor alpha receptor immunoglobulin and beta-galactosidase were readministered once (7 days after the first adenovirus administration) or twice (on days 7 and 14; n = 4/day). A 2-way factorial analysis of variance was used for statistical analysis. RESULTS: Soluble tumor necrosis factor alpha receptor immunoglobulin and beta-galactosidase cotransfection prolonged the duration of beta-galactosidase expression. However, antiadenovirus antibody production was significantly increased in the cotransfection group. In addition, there was no increase in beta-galactosidase expression after readministration of soluble tumor necrosis factor alpha receptor immunoglobulin and beta-galactosidase. CONCLUSION: Adenoviral vector encoding soluble tumor necrosis factor alpha receptor immunoglobulin and beta-galactosidase cotransfection prolongs beta-galactosidase expression but does not increase beta-galactosidase expression after repeated administration. These results suggest that tumor necrosis factor alpha is one of the most important factors in regulating the duration of gene expression. The cotransfection approach is feasible, but the increase of antiadenovirus antibodies might make repeated cotransfection unfeasible.

Adenoviridae↗
PubMed2002

Space-time encoding for high frame rate ultrasound imaging.

Frame rate in ultrasound imaging can be dramatically increased by using sparse synthetic transmit aperture (STA) beamforming techniques. The two main drawbacks of the method are the low signal-to-noise ratio (SNR) and the motion artifacts, that degrade the image quality. In this paper we propose a spatio-temporal encoding for STA imaging based on simultaneous transmission of two quasi-orthogonal tapered linear FM signals. The excitation signals are an up- and a down-chirp with frequency division and a cross-talk of -55 dB. The received signals are first cross-correlated with the appropriate code, then spatially decoded and finally beamformed for each code, yielding two images per emission. The spatial encoding is a Hadamard encoding previously suggested by Chiao et al. [in: Proceedings of the IEEE Ultrasonics Symposium, 1997, p. 1679]. The Hadamard matrix has half the size of the transmit element groups, due to the orthogonality of the temporal encoded wavefronts. Thus, with this method, the frame rate is doubled compared to previous systems. Another advantage is the utilization of temporal codes which are more robust to attenuation. With the proposed technique it is possible to obtain images dynamically focused in both transmit and receive with only two firings. This reduces the problem of motion artifacts. The method has been tested with extensive simulations using Field II. Resolution and SNR are compared with uncoded STA imaging and conventional phased-array imaging. The range resolution remains the same for coded STA imaging with four emissions and is slightly degraded for STA imaging with two emissions due to the -55 dB cross-talk between the signals. The additional proposed temporal encoding adds more than 15 dB on the SNR gain, yielding a SNR at the same order as in phased-array imaging.

Journal Article↗
PubMed2001

The high molecular mass rhoptry protein, RhopH1, is encoded by members of the clag multigene family in Plasmodium falciparum and Plasmodium yoelii.

Malarial merozoite rhoptries contain a high molecular mass protein complex called RhopH. RhopH is composed of three polypeptides, RhopH1, RhopH2, and RhopH3, encoded by distinct genes. Using monoclonal antibody-purified protein complex from both Plasmodium falciparum and Plasmodium yoelii, peptides were obtained by digestion of RhopH1 and their sequence determined either by mass spectrometry or Edman degradation. In both species the genes encoding RhopH1 were identified as members of the cytoadherence linked asexual gene (clag) family. In P. falciparum the family members on chromosome 3 were identified as encoding RhopH1. In P. yoelii two related genes were identified and sequenced. One of the genes, pyrhoph1a, was positively identified as encoding RhopH1 by the peptide analysis and the other gene, pyrhoph1a-p, was at least transcribed. Genes in the clag family present in both parasite species have a number of conserved features. The size and location of the P. yoelii protein complex in the rhoptries was confirmed. The first clag gene identified on chromosome 9 was implicated in cytoadherence, the binding of infected erythrocytes to host endothelial cells; this study shows that other members of the family encode merozoite rhoptry proteins, proteins that may be involved in merozoite-erythrocyte interactions. We propose that the family should be renamed as rhoph1/clag.

Amino Acid Sequence↗
PubMed2003

Molecular cloning of genes encoding oncosphere proteins reveals conservation of modular protein structure in cestode antigens.

Recombinant oncosphere antigens have been found to be remarkably effective when used as vaccines against cysticercosis and hydatid disease. Comparison of the structural features of these proteins and their associated genes suggest common features between antigens. Here molecular cloning is used to complete comparisons of Taenia solium, Taenia saginata, Taenia ovis, Echinococcus granulosus and Echinococcus multilocularis oncosphere antigens and genes. The exon/intron structure of genes cloned from T. solium and T. ovis genomic DNA (tsol16 and to16, respectively) in this study was found to be highly conserved. Two closely related tsol16 genes were cloned from the T. solium genome. Their corresponding transcripts were cloned from T. solium oncospheres and a comparison of their deduced amino-acid sequence with that of the protein encoded by to16 indicates that these proteins are the most highly conserved oncosphere proteins identified so far. Cloning of another gene from T. solium (designated tsol18) and comparison with the homologous gene of T. saginata (tsa18) also revealed substantial conservation of gene structure. Comparisons of the genes cloned in this study with genes encoding oncosphere antigens from other taeniid cestodes identified striking conservation of exon structure. The highly conserved regions of the genes encode a putative secretory signal and fibronectin type III domain in each of the oncosphere proteins. The location of exon boundaries in relation to protein features identifies a clear modular structure among all members of these oncosphere antigens. Identification of structural conservation of genes encoding antigenic proteins across several taeniid species suggests that the encoded proteins play important roles in host infection and parasite survival.

Animals↗
PubMed2002

Encoding-related brain activity during deep processing of verbal materials: a PET study.

The recent advent of neuroimaging techniques provides an opportunity to examine brain regions related to a specific memory process such as episodic memory encoding. There is, however, a possibility that areas active during an assumed episodic memory encoding task, compared with a control task, involve not only areas directly relevant to episodic memory encoding processes but also areas associated with other cognitive processes for on-line information. We used positron emission tomography (PET) to differentiate these two kinds of regions. Normal volunteers were engaged in deep (semantic) or shallow (phonological) processing of new or repeated words during PET. Results showed that deep processing, compared with shallow processing, resulted in significantly better recognition performance and that this effect was associated with activation of various brain areas. Further analyses revealed that there were regions directly relevant to episodic memory encoding in the anterior part of the parahippocampal gyrus, inferior frontal gyrus, supramarginal gyrus, anterior cingulate gyrus, and medial frontal lobe in the left hemisphere. Our results demonstrated that several regions, including the medial temporal lobe, play a role in episodic memory encoding.

Adult↗
PubMed1997

Decreased expression of nuclear and mitochondrial DNA-encoded genes of oxidative phosphorylation in association neocortex in Alzheimer disease.

We recently reported 50% decreases in mRNA levels of mitochondrial DNA (mtDNA)-encoded cytochrome oxidase (COX) subunits I and III in Alzheimer disease (AD) brains. The decreases were observed in an association neocortical region (midtemporal cortex) affected in AD, but not in the primary motor cortex unaffected in AD. To investigate whether the decreases are specific to mtDNA-encoded mRNA, we extended this analysis to nuclear DNA (nDNA)-encoded subunits of mitochondrial enzymes of oxidative phosphorylation (OXPHOS). Brains from five AD patients showed 50-60% decreases in mRNA levels of nDNA-encoded subunit IV of COX and the beta-subunit of the F0F1-ATP synthase in midtemporal cortex compared with mRNA levels from midtemporal cortex of control brains. In contrast, these mRNAs were not reduced in primary motor cortices of the AD brains. The amount of nDNA-encoded beta-actin mRNA and the amount of 28S rRNA were not altered in either region of the AD brain. The results suggest that coordinated decreases in expression of mitochondrial and nuclear genes occur in association cortex of AD brains and are a consequence of reduced neuronal activity and downregulation of OXPHOS machinery.

Aged↗
PubMed2001

Plasmids encoding granulocyte-macrophage colony-stimulating factor and CD154 enhance the immune response to genetic vaccines.

We examined whether plasmids encoding granulocyte-macrophage colony-stimulating factor (pGM-CSF) or CD40-ligand (pCD40L) could modify the immune response to antigen encoded by co-injected plasmid DNA. For this we used as antigen Escherichia coli beta galactosidase (beta-gal), encoded by the plasmid pLacZ. We found that intradermal co-injection of pLacZ with both pGM-CSF and pCD40L enhanced the anti-beta-gal IgG response by approximately two orders of magnitude compared to injections of pLacZ alone. Co-injection of both pGM-CSF and pCD40L with pLacZ significantly enhanced antigen-specific IgG, and in particular IgG(2a), over that of animals co-injected with pLacZ and either pGM-CSF or pCD40L. We found that co-injection of pGM-CSF and pCD40L with pLacZ enhanced the generation of beta-gal-specific cytotoxic T cells, and allowed for a significant expansion of CD8(+) T cells from splenocytes co-cultured with beta-gal expressing stimulator cells. The immunostimulatory effects induced by pGM-CSF or pCD40L required injection of these plasmids to the same site that received pLacZ. 'Priming' experiments, where the site of injection was pre-injected with either plasmid adjuvant, showed that pGM-CSF, but not pCD40L, could enhance the anti-beta-gal immune response induced by subsequently administered plasmid antigen. We conclude that plasmids encoding GM-CSF and CD154 are particularly effective genetic adjuvants when used together to enhance the humoral and cellular immune response to a plasmid-encoded antigen.

Adjuvants, Immunologic↗