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Biomedical subjects

Michel Denis

Publications and source records attributed to Michel Denis.

At least 19 recordsLinked to original sources
PubMed2006

Bactericidal activity of macrophages against Streptococcus uberis is different in mammary gland secretions of lactating and drying off cows.

The aim of this study was to compare the ability of milk macrophages and macrophages from the mammary gland secretions during the mid-dry period for their interaction with the mastitis-causing Streptococcus uberis. We also aimed to determine if S. uberis induced the release of the cytokine tumour necrosis alpha (TNF-alpha) and the bactericidal moiety nitric oxide (NO) from milk macrophages of lactating cows and macrophages from the mammary gland secretions at the mid-dry period. Macrophages were isolated from the mammary gland secretions of cows during the mid-lactation or mid-dry period, and compared with blood monocytes for their interaction with the important mastitis-causing pathogen S. uberis. When infected in vitro with S. uberis, milk macrophages from lactating cows with S. uberis released modest amounts of the cytokine tumour necrosis factor alpha (TNF-alpha) (139 pg/ml) and the bactericidal moiety nitric oxide (NO) (3-4 microM of nitrite). Blood monocytes from lactating cows released significantly higher amounts of TNF-alpha (345 +/- 143 pg/ml) and NO (7 +/- 2 microM of nitrite) after interaction with S. uberis, compared to milk macrophages (P < 0.01 for both TNF-alpha and NO). Stimulation of blood monocytes with the cytokine interferon-gamma (IFN-gamma) enhanced significantly the release of NO and TNF-alpha, but IFN-gamma did not significantly enhance the production of NO and TNF-alpha by milk macrophages from lactating cows. Milk macrophages from all lactating cows failed to kill S. uberis efficiently, and this lack of killing was unaffected by prior treatment with gamma interferon (IFN-gamma) (P > 0.05). Rather, S. uberis multiplied significantly inside infected milk macrophages from lactating cows, with a two-fold increase in bacterial numbers at 2 h post-infection. Milk macrophages from lactating cows were able however, to kill a significant proportion (50-60%, P < 0.01) of phagocytosed Staphylococcus aureus. Blood monocytes from all cows were found to exert significant bactericidal activity against S. uberis. There were no significant differences in the bactericidal activity of milk macrophages obtained from lactating cows with low somatic cell counts (SCC; < 10(5) ml(-1)) compared with those with a mildly elevated SCC (> 10(5) ml(-1)) (P > 0.05). In contrast, mammary gland secretion macrophages isolated from the same cows in the mid-dry period killed a significant proportion of phagocytosed S. uberis (50-65% of ingested S. uberis killed, P < 0.01) although cytokine production in response to in vitro bacterial infection was low. We conclude that the bactericidal activity of mammary gland secretion macrophages against a virulent strain of S. uberis is low during the lactation period. In addition, our data indicate that S. uberis is not a strong inducer of NO and TNF-alpha in macrophages from the milk or mammary gland secretions of cows during the drying off period. Finally, IFN-gamma does not activate milk macrophages or macrophages from cows during the lactating period or mammary gland secretions during the drying off period.

Animals↗
PubMed2006

Phosphatidylinositol mannosides: synthesis and adjuvant properties of phosphatidylinositol di- and tetramannosides.

Phosphatidylinositol mannosides (PIMs) isolated from mycobacteria have been identified as an important class of glycolipids with significant immune modulating properties. We present here the syntheses of phosphatidylinositol dimannoside (PIM2, 1) and phosphatidylinositol tetramannoside (PIM4, 2) and evaluate their adjuvant properties in a transgenic mouse model. The key step in the synthetic methodology for the synthesis of 2 relies on the selective glycosylation of diol 3 with mannosyl donor 11. Both synthetic PIMs were effective at enhancing IFN-gamma when given as adjuvants with a model antigen, with PIM2 being the more active. These data suggest that in this assay the PIM core structure is responsible for the observed biological activity.

Adjuvants, Immunologic↗
PubMed2006

Bovine natural killer cells restrict the replication of Mycobacterium bovis in bovine macrophages and enhance IL-12 release by infected macrophages.

In this contribution, the impact of bovine natural killer (NK) cells on resistance to bovine tuberculosis was studied, using a monoclonal antibody against bovine NKp46. NK cells cultured with M. bovis-infected macrophages, but not control uninfected macrophages, proliferated and released IFN-gamma. Blood monocyte-derived macrophages were infected with virulent M. bovis, and growth of intra-macrophage bacteria was monitored by incorporation of tritiated uracil. Co-culturing infected macrophages with autologous NK cells significantly reduced the intracellular bacterial growth. Stimulation of NK cells with interleukin-2 (IL-2) enhanced further the capacity of these cells to reduce M. bovis replication in infected macrophages. NK cells from both BCG vaccinated and unvaccinated animals mediated this intra-macrophage growth restriction at similar levels. The ability of NK cells to reduce bacterial growth was independent of the release of IFN-gamma, as blocking IFN-gamma with an antibody in vitro did not affect intra-macrophage bacterial growth. NK cells reduced bacterial growth and also increased macrophage release of interleukin-12 (IL-12) and nitric oxide (NO) production by M. bovis-infected macrophages. Neutralizing NO production by macrophages in vitro with mono-methyl-l-arginine (MMLA) did not abrogate the ability of NK cells to decrease bacterial growth in infected macrophages. Reduction of mycobacterial intra-macrophage growth by NK cells was dependent on direct contact between NK cells and infected macrophages. Supernatants from NK cells failed to impact significantly on M. bovis replication in infected macrophages. The reduction in bacterial growth in macrophages correlated with the induction of an apoptosis program in infected macrophages. Cell death occurred at a similar rate in infected macrophages, exposed to NK cells or not. We conclude that bovine NK cells are stimulated by and release IFN-gamma in response to infected cells and reduce M. bovis growth in infected macrophages by an unclear mechanism, and are potentially involved in innate resistance of cattle to tuberculosis.

Animals↗
PubMed2006

Comparing distances in mental images constructed from visual experience or verbal descriptions: the impact of survey versus route perspective.

Mental images constructed after visual examination of a spatial configuration or after processing a verbal description of that configuration have been shown to share similar properties, in particular the capacity to preserve metric information contained in the configuration represented. In the present study, we investigated the properties of mental images constructed under learning conditions resulting from the combination of a visual or a verbal mode of acquisition and a survey or route perspective. Participants memorized a virtual environment (a garden containing six objects) under one of four learning conditions: (a) viewing a map of the garden (visual-survey); (b) viewing a video presentation of a journey along the path around the garden (visual-route); (c) listening to a verbal description of the map of the garden (verbal-survey); and (d) listening to a verbal description of the journey around the garden (verbal-route). The participants were then invited to compare the distances separating objects in the garden mentally. Experiment 1, where the pairs of distances to be compared had a common starting point, revealed that the frequency of correct responses was higher, and response times were shorter when participants had learned about the environment visually rather than by a verbal description. The conditions involving a survey perspective resulted in a higher frequency of correct responses and shorter response times than those involving a route perspective. Lastly, a symbolic distance effect was obtained in the first three conditions, in that the greater the difference between the two distances being compared, the higher the frequency of correct responses, and the shorter the response times. Experiment 2, where the pairs of distances had different starting points, replicated these results, although longer response times revealed that the comparison process was more costly. Taken together, these findings support the view that mental spatial representations derived from different sources and adopting different perspectives contain genuine metric properties, except when the verbal modality and the route perspective are combined during learning.

Adolescent↗
PubMed2006

The bactericidal effect of TiO2 photocatalysis involves adsorption onto catalyst and the loss of membrane integrity.

The bactericidal effect of photocatalysis with TiO2 is well recognized, although its mode of action is still poorly characterized. It may involve oxidation, as illuminated TiO2 generates reactive oxygen species. Here we analyze the bactericidal effect of illuminated TiO2 in NaCl-KCl or sodium phosphate solutions. We found that adsorption of bacteria on the catalyst occurred immediately in NaCl-KCl solution, whereas it was delayed in the sodium phosphate solution. We also show that the rate of adsorption of cells onto TiO2 is positively correlated with its bactericidal effect. Importantly, adsorption was consistently associated with a reduction or loss of bacterial membrane integrity, as revealed by flow cytometry. Our work suggests that adsorption of cells onto aggregated TiO2, followed by loss of membrane integrity, is key to the bactericidal effect of photocatalysis.

Adsorption↗
PubMed2006

Relationship among several key cell cycle events in the developmental cyanobacterium Anabaena sp. strain PCC 7120.

When grown in the absence of a source of combined nitrogen, the filamentous cyanobacterium Anabaena sp. strain PCC 7120 develops, within 24 h, a differentiated cell type called a heterocyst that is specifically involved in the fixation of N(2). Cell division is required for heterocyst development, suggesting that the cell cycle could control this developmental process. In this study, we investigated several key events of the cell cycle, such as cell growth, DNA synthesis, and cell division, and explored their relationships to heterocyst development. The results of analyses by flow cytometry indicated that the DNA content increased as the cell size expanded during cell growth. The DNA content of heterocysts corresponded to the subpopulation of vegetative cells that had a big cell size, presumably those at the late stages of cell growth. Consistent with these results, most proheterocysts exhibited two nucleoids, which were resolved into a single nucleoid in most mature heterocysts. The ring structure of FtsZ, a protein required for the initiation of bacterial cell division, was present predominantly in big cells and rarely in small cells. When cell division was inhibited and consequently cells became elongated, little change in DNA content was found by measurement using flow cytometry, suggesting that inhibition of cell division may block further synthesis of DNA. The overexpression of minC, which encodes an inhibitor of FtsZ polymerization, led to the inhibition of cell division, but cells expanded in spherical form to become giant cells; structures with several cells attached together in the form of a cloverleaf could be seen frequently. These results may indicate that the relative amounts of FtsZ and MinC affect not only cell division but also the placement of the cell division planes and the cell morphology. MinC overexpression blocked heterocyst differentiation, consistent with the requirement of cell division in the control of heterocyst development.

Anabaena↗
PubMed2006

Visuospatial working memory and the processing of spatial descriptions.

The dual-task paradigm was used to determine whether the spatial, visual and verbal components of working memory are engaged in the processing of spatial descriptions. Participants listened to route or survey descriptions of urban-like spatial environments and then drew corresponding maps. The position of each new landmark was described either in terms of the direction to move toward this landmark (route descriptions) or its relative location with regard to the previously mentioned landmark (survey descriptions). Route and survey descriptions resulted in similar recall performance in the absence of an interfering task and landmarks were consistently less well recalled than their associated moves/locations. The pattern of interference resulting from the secondary tasks indicated that the processing of landmarks called upon both the visual and spatial components of working memory in the route perspective, whereas the processing of moves/locations essentially relied on the spatial component in both the route and the survey perspectives. The verbal component of working memory was only involved in the processing of landmarks in the survey perspective. The results suggest that distinct cognitive processes support memory for route and survey descriptions, and that distinct working memory resources support the processing of landmarks and landmark positions.

Adult↗
PubMed2006

Different cognitive processes in two image-scanning paradigms.

Mental image scanning is generally assumed to be a single process that allows people to shift attention across visualized objects. However, this implicit assumption is open to question. We report a set of three experiments based on the tasks originally designed by Kosslyn, Ball, and Reiser (1978) and Finke and Pinker (1982). Participants scanned the identical images of an array of dots in the two tasks. Nevertheless, the participants required more time to shift their focus over the imaged stimulus in the Kosslyn et al. (1978) paradigm. Moreover, correlational analyses revealed no consistent relationship between the slopes of the increases in scanning times with increasing distances in the two paradigms. We conclude that in the Kosslyn et al. (1978) paradigm, the participants draw primarily on transformational processes to scan, whereas in the Finke and Pinker (1982) paradigm, they draw primarily on attentional processes. Both processes, transforming the image and shifting an attention window, produce linear increases in time with increases in distance, but for different reasons.

Adult↗
PubMed2005

Identification of immune response correlates for protection against bovine tuberculosis.

Identification of an immune response correlate for protection against bovine tuberculosis would greatly facilitate the rational development of an effective vaccine. However, finding such a correlate has been a daunting task. Vaccination/challenge studies in cattle provide an ideal platform to compare induction of immune response parameters following vaccination and challenge, and assess the correlation of these parameters with protection. Protection against tuberculosis requires a Th 1-type cell-mediated immune response and induction of an antigen-specific interferon-gamma (IFN-gamma) response was the logical first choice in an investigation to identify an immune response correlate for protection. Calf vaccination studies showed that the subcutaneous injection of BCG vaccine induced significant protection against experimental challenge with Mycobacterium bovis. This protection was associated with strong whole blood IFN-gamma responses to bovine PPD 2-4 weeks after vaccination, but within the BCG-vaccinated groups, these responses were not correlated with protection. Use of a variety of vaccination strategies has shown that IFN-gamma responses in isolation were not necessarily associated with protection and concurrent IL-4 mRNA expression or antibody responses could also be induced. Collation of an immunological profile may be more informative than a study of individual cytokines. An indication of vaccine efficacy can be provided by the study of immune responses following challenge of the calves with M. bovis. IFN-gamma responses to ESAT-6, antibody responses following tuberculin skin testing and antigen-specific IL-4 mRNA expression all correlated with the severity of disease and indirectly provided an indication of protection. Future studies should be directed towards obtaining immunological profiles of calves following vaccination using techniques such as DNA microarray analysis, measurement of cytokine mRNA expression by real-time PCR, protein profiling by SELDI-TOF mass spectrometry as well as determining cytokine production by specific T cell sub-sets in individual protected animals.

Animals↗
PubMed2005

Iron modulates the replication of virulent Mycobacterium bovis in resting and activated bovine and possum macrophages.

Bovine and possum macrophages were infected in vitro with a virulent strain of Mycobacterium bovis, and mycobacterial replication was measured in the infected macrophages cultured under a variety of conditions. Virulent M. bovis replicated substantially in alveolar possum macrophages as well as in bovine blood monocyte-derived macrophages. Addition of recombinant bovine interferon-gamma (IFN-gamma) with low concentrations of lipopolysaccharide (LPS) rendered bovine macrophages significantly more resistant to M. bovis replication. Disruption of iron levels in infected macrophages by addition of apotransferrin or bovine lactoferrin blocked replication of M. bovis in both bovine and possum macrophages. On the other hand, addition of exogenous iron, either in the form of iron citrate or iron-saturated transferrin, rendered macrophages of both species much more permissive for the replication of M. bovis. The impact of iron deprivation/loading on the mycobacteriostatic activity of cells was independent of nitric-oxide release, as well as independent of the generation of oxygen radical species in both possum and bovine macrophages. Exogenous iron was shown to reverse the ability of IFN-gamma/LPS pulsed bovine macrophages to restrict M. bovis replication. When autologous possum lymphocytes from animals vaccinated with M. bovis strain BCG were added to infected macrophages, they rendered the macrophages less permissive for virulent M. bovis replication. Loading the cells with iron prior to this macrophage-lymphocyte interaction, reversed this immune effect induced by sensitized cells. We conclude that, in two important animal species, intracellular iron level plays an important role in M. bovis replication in macrophages, irrespective of their activation status.

Animals↗
PubMed2005

Effect of oral vaccination of cattle with lipid-formulated BCG on immune responses and protection against bovine tuberculosis.

Cattle were given Mycobacterium bovis bacillus Calmette-Guerin (BCG) in a lipid-based formulation via the oral route and tested for immune responses and protection against a challenge with virulent M. bovis. Calves were vaccinated by orally administering a pellet containing 10(8) colony forming units (CFU) of BCG, or 10 pellets containing a total of 10(9) CFU of BCG, whereas positive controls were injected subcutaneously with 10(6) CFU of BCG. All of the subcutaneously vaccinated calves produced positive responses in the caudal fold tuberculin skin test at 8 weeks after vaccination, whereas only 3/9 of the low dose and 6/10 of the high dose orally-vaccinated animals produced positive reactions. None of the animals produced positive reactions to the mycobacterial antigens, ESAT-6 and CFP10 in the interferon-gamma (IFN-gamma) test and only a total of four of the BCG-vaccinated animals produced positive responses in either the standard IFN-gamma or comparative cervical skin test. Oral administration of 10 pellets of lipid-formulated BCG to cattle induced a significant level of protection against bovine tuberculosis compared to that observed in non-vaccinated animals and this level was similar to that seen in the BCG subcutaneously vaccinated animals. Oral vaccination of BCG in a lipid-formulation to calves was shown to induce some positive tuberculin skin test reactions, but could also induce protection against bovine tuberculosis.

Adjuvants, Immunologic↗
PubMed2005

Susceptibility of brushtail possums (Trichosurus vulpecula) infected with Mycobacterium bovis is associated with a transient macrophage activation profile.

The Australian brushtail possums are highly susceptible to Mycobacterium bovis and are the principal wildlife reservoir of M. bovis in New Zealand. To better understand the disease process in these animals, brushtail possums were infected by the aerosol route with a virulent strain of M. bovis, and immune parameters measured. M. bovis replicated actively in the lungs of infected animals. Animals began developing macroscopic lung lesions at 4 and 5 weeks following infection, with some lesions appearing in the livers and spleens. Infection determined the emergence of blood lymphocytes which proliferated in response to bovine purified protein derivative from M. bovis (PPD-b) at 3, 4 and 5 weeks. The response to a mitogen (Concanavalin A) waned progressively with time. Infection was associated with a modest increase in the numbers of free lung cells. Nitrite was detectable in the lavage fluids of infected animals at 3 weeks postinfection, but not at 4 and 5 weeks. Macrophage activation in the lungs was evident as alveolar macrophages produced more oxidants, significant levels of nitric oxide (NO), as well as tumor necrosis factor alpha (TNF-alpha) bioactivity at 3 weeks postinfection. However, macrophages from infected animals lost the ability to generate nitrite- and TNF-alpha generation was depressed at 4 and 5 weeks postinfection, the time at which macroscopic lesions in the lungs became apparent. Alveolar macrophages from animals at 3 weeks postinfection blocked the replication of M. bovis in part via a NO-dependent mechanism, and were more refractory for M. bovis growth than cells from naïve animals to bacterial replication. Alveolar macrophages from animals at 4 and 5 weeks postinfection allowed substantial replication of M. bovis, and no NO-dependent bacteriostatic activity was apparent. Introduction of autologous lymphocytes from the blood of infected animals in co-cultures rendered infected macrophages more resistant to M. bovis replication. We conclude that M. bovis infection in brushtail possums is associated with a transient activation of alveolar macrophages, although in vitro exposure to sensitized T cells can enhance this profile.

Animals↗
PubMed2005

Ability of T cell subsets and their soluble mediators to modulate the replication of Mycobacterium bovis in bovine macrophages.

Peripheral blood mononuclear cells (PBMCs) from cattle vaccinated with Bacillus Calmette-Guerin (BCG) were obtained and expanded in vitro by incubation with purified protein derivative. The ability of these cells to modulate the replication of virulent Mycobacterium bovis in autologous-infected macrophages was compared to cells from non-vaccinated controls. Cells from non-vaccinated animals were shown to confer a significant degree of mycobacteriostatic activity to autologous-infected macrophages. This activity was not inhibited by including a neutralizing antibody versus interferon-gamma (IFN-gamma), and was dependent on direct contact between PBMCs and infected macrophages. Addition of autologous PBMCs from BCG-vaccinated cattle was shown to significantly enhance macrophage resistance to M. bovis, and this increased macrophage resistance was partly abrogated by including a neutralizing antibody to IFN-gamma. Addition of T cells from non-vaccinated animals to infected macrophages was associated with a modest increase in macrophage release of TNF-alpha and nitric oxide, whereas PBMCs from vaccinated animals increased very significantly the release of these factors. Neutralization of nitric oxide (NO), by inclusion of monomethyl-L-arginine, significantly diminished the ability of PBMCs from vaccinated animals to enhance macrophage resistance to M. bovis, but had no impact on the ability of T cells from naive animals to modulate macrophage function. The ability of naive cells to increase macrophage anti-M. bovis activity was largely mediated by CD4+ T cells, whereas both CD4+ T cells and CD8+ T cells conferred macrophage resistance to M. bovis in vaccinated animals. These data highlight the role of IFN-gamma and NO in the immune resistance of cattle to M. bovis.

Animals↗
PubMed2005

Vaccination of brushtail possums, Trichosurus vulpecula, with Bacille Calmette-Guerin induces T lymphocytes that reduce Mycobacterium bovis replication in alveolar macrophages via a contact-dependent/nitric oxide-independent mechanism.

The permissiveness of alveolar macrophages from brushtail possums for the replication of Mycobacterium bovis was examined. Mycobacterium bovis replication was indirectly measured by assessing bacterial metabolism via the incorporation of [3-H]-uracil by bacilli released from lysed macrophages previously infected with mycobacteria. Alveolar macrophages allowed substantial replication of virulent M. bovis, in contrast to Bacille Calmette-Guerin (BCG) Pasteur, which replicated poorly. The addition of crude lymphokines enhanced the metabolic activity of phagocytosed M. bovis in possum macrophages. Possum lymphokines enhanced the ability of possum macrophages to generate reactive oxygen intermediates, measured by the reduction of nitroblue tetrazolium, which is indicative of an activation process. Similarly, the addition of recombinant possum TNF-alpha enhanced the permissiveness of alveolar macrophages for M. bovis. In contrast to mouse peritoneal macrophages, possum alveolar macrophages did not release significant levels of nitric oxide (NO) after stimulation with M. bovis and/or lymphokines. However, the uptake of virulent M. bovis by possum macrophages was associated with an enhanced ability of cells to release TNF-alpha, whereas very low levels of TNF-alpha were released after infection with BCG. The addition of a selective inhibitor of inducible NO synthase had no impact on the replication of M. bovis or BCG in possum macrophages in the presence or absence of lymphokines. Co-culturing infected possum alveolar macrophages with autologous blood mononuclear cells from BCG-vaccinated possums led to a significant decrease in the metabolic activity of intracellular M. bovis. This effect was contact dependent and NO independent and was mediated by a population of CD3+ cells. In addition, adding scavengers of reactive oxygen intermediates did not abrogate this phenomenon.

Animals↗
PubMed2005

IFN-gamma enhances bovine macrophage responsiveness to Mycobacterium bovis: Impact on bacterial replication, cytokine release and macrophage apoptosis.

We sought to determine the impact of bovine IFN-gamma on the interaction between Mycobacterium bovis and bovine macrophages. Bovine macrophages released small amounts of nitric oxide (NO), TNF-alpha, IL-1beta and IL-12 upon infection with bacille Calmette-Guérin (BCG). Prior pulsing of cells with IFN-gamma significantly enhanced the release of NO and IL-12. Infection of bovine macrophages with virulent M. bovis led to the release of higher levels of pro-inflammatory mediators, compared to levels released upon BCG infection. IFN-gamma treatment of macrophages enhanced the release of pro-inflammatory mediators, but did not modify bacterial replication in M. bovis-infected macrophages. Treatment of macrophages with a combination of IFN-gamma and LPS led to a reduction in bacterial replication. Infected cells treated with IFN-gamma/LPS progressed mostly through an apoptotic pathway, whereas untreated infected cells eventually died by necrosis. Agents that prevented the acquisition of bacteriostatic activity by activated macrophages also prevented the induction of apoptosis in infected macrophages (IL-10 and neutralizing anti-TNF-alpha). We conclude that virulent M. bovis is a major determinant of release of pro-inflammatory cytokines by macrophages. IFN-gamma amplifies the macrophage cytokine release in response to M. bovis. Induction of apoptosis is closely linked to the emergence of macrophage resistance to M. bovis replication, which is dependent on endogenous TNF-alpha release.

Animals↗
PubMed2005

Vaccination of cattle with a CpG oligodeoxynucleotide-formulated mycobacterial protein vaccine and Mycobacterium bovis BCG induces levels of protection against bovine tuberculosis superior to those induced by vaccination with BCG alone.

The development of a subunit protein vaccine for bovine tuberculosis which could be used either in combination with Mycobacterium bovis BCG (to improve the efficacy of that vaccine) or alone would offer significant advantages over currently available strategies. A study was conducted with cattle to determine the protective efficacy of a strategy based on concurrent immunization with an M. bovis culture filtrate (CFP) vaccine and BCG compared to vaccination with either vaccine alone. One group of calves (10 animals per group) was vaccinated subcutaneously with CFP formulated with Emulsigen and combined with a CpG oligodeoxynucleotide (ODN). A second group was vaccinated with both the CFP vaccine and BCG injected at adjacent sites (CFP-BCG). One further group was vaccinated subcutaneously with BCG, while another group served as nonvaccinated control animals. Vaccination with CFP-BCG induced levels of antigen-specific gamma interferon (IFN-gamma) and interleukin-2 (IL-2) in whole-blood cultures that were higher than those induced by vaccination with BCG alone. The combination of CFP and BCG did not enhance the production of antibodies to M. bovis CFP compared to vaccination with CFP alone. Vaccination with CFP alone led to delayed antigen-specific IFN-gamma and IL-2 responses. Vaccination with CFP-BCG induced a high level of protection against an intratracheal challenge with virulent M. bovis, based on a significant enhancement of six pathological and microbiological parameters of protection compared with the nonvaccinated group. In contrast, vaccination with BCG alone induced a significant enhancement of protection in only one parameter, while CFP alone induced no protection. These results suggest that a combination of a CpG ODN-formulated protein vaccine and BCG offers better protection against bovine tuberculosis than does BCG alone.

Adjuvants, Immunologic↗
PubMed2004

Retinotopic organization of visual mental images as revealed by functional magnetic resonance imaging.

In this study, we used event-related functional magnetic resonance imaging to investigate whether visual mental images retinotopically activate early visual cortex. Six participants were instructed to visualize or view horizontally or vertically oriented flashing bow-tie shaped stimuli. When compared to baseline, imagery globally activated Area V1. When the activation evoked by the stimuli at the different orientations was directly compared, distinct spatial activation patterns were obtained for each orientation in most participants. Not only was the topography of the activation patterns from imagery similar to the topography obtained with a corresponding visual perception task, but it closely matched the individual cortical representation of either the horizontal or the vertical visual field meridians. These findings strongly support that visual imagery and perception share low-level anatomical substrate and functional processes. Binding of spatial features is suggested as one possible mechanism.

Acoustic Stimulation↗