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Biomedical subjects

P Andersen

Publications and source records attributed to P Andersen.

At least 37 records · Page 2Linked to original sources
PubMed2002

Detunable transverse electromagnetic (TEM) volume coil for high-field NMR.

Most high-field MRI systems do not have the actively detuned body coils that are integral to clinical systems operating at 1.5T and lower field strengths. Therefore, many clinical applications requiring homogeneous volume excitation in combination with local surface coil reception are not easily implemented at high fields. To solve this problem for neuroimaging applications, actively detunable transverse electromagnetic (TEM) head coils were developed to be used with receive-only surface coils for signal-to-noise ratio (SNR) gains and improved spatial coverage from homogeneously excited regions. These SNR and field of view (FOV) gains were achieved by application of a detunable TEM volume coil to human brain imaging at 4T.

Brain↗
PubMed2002

Effect of different adjuvants on the immune responses of cattle vaccinated with Mycobacterium tuberculosis culture filtrate proteins.

The development of improved vaccines for bovine tuberculosis is urgently required as a cost effective solution for control and eventual eradication of tuberculosis in domestic animals. Studies in small animal models of tuberculosis have shown that vaccination with culture filtrate proteins (CFP), prepared from Mycobacterium tuberculosis or M. bovis, can induce cellular immune responses and confer a level of protection against aerogenic challenge with virulent mycobacteria. As a first step in the development of a mycobacterial CFP vaccine for protection of cattle against bovine tuberculosis, the immune responses of cattle vaccinated with short-term culture filtrate proteins (ST-CFP) from M. tuberculosis and formulated with different adjuvants were compared with those vaccinated with bacille Calmette-Guerin (BCG). The adjuvants included dimethyldioctyldecyl ammonium bromide (DDA), diethylaminoethyl (DEAE)-dextran, and ST-CFP adsorbed onto polystyrene beads. Vaccination with ST-CFP/DEAE-dextran induced high levels of interleukin-2 (IL-2) but low levels of interferon-gamma (IFN-gamma) from whole-blood cultures stimulated with M. tuberculosis ST-CFP in comparison with the strong IFN-gamma and IL-2 responses induced after vaccination with BCG. ST-CFP/DEAE-dextran also induced a strong antigen-specific immunoglobulin antibody response with both immunoglobulin G1 (IgG1) and IgG2 isotypes. Vaccination with ST-CFP/beads induced a weak IgG1-biased antibody response but no IFN-gamma or IL-2 response. DDA did not induce significant immune responses in animals vaccinated with ST-CFP. In comparison to the moderate delayed-type hypersensitivity (DTH) responses induced by vaccination with subcutaneous BCG, none of the ST-CFP vaccines induced a significant DTH response to either M. tuberculosis ST-CFP or bovine purified protein derivative (PPD). While the ST-CFP vaccines used in this study have not induced strong antigen-specific cellular immune responses in cattle comparable to those induced by BCG, they are immunogenic in cattle and it may be possible to overcome this problem by using adjuvants that more effectively promote IFN-gamma responses in this species.

Adjuvants, Immunologic↗
PubMed2002

Specific acquired resistance in mice immunized with killed mycobacteria.

Past attempts to raise resistance against Mycobacterium tuberculosis using various preparations of killed mycobacteria have questioned the specificity of the generated immune response. In the present study, we have focused on the protective efficacy of experimental vaccines based on killed mycobacteria. We demonstrate that killed mycobacteria can confer high levels of protection, which can be adoptively transferred to recipient T-cell-deficient mice. Moreover, protective antigens can be found in the cell wall, membrane and cytosol of the mycobacterial cell, and hence emphasize the importance of searching for protective antigens in various compartments of the mycobacterial cell.

Adoptive Transfer↗
PubMed2001

Divergent effect of bacillus Calmette-Guérin (BCG) vaccination on Mycobacterium tuberculosis infection in highly related macaque species: implications for primate models in tuberculosis vaccine research.

Despite the widespread use of bacillus Calmette-Guérin vaccination, Mycobacterium tuberculosis infection remains globally the leading cause of death from a single infectious disease. The complicated and often protracted dynamics of infection and disease make clinical trials to test new tuberculosis vaccines extremely complex. Preclinical selection of only the most promising candidates is therefore essential. Because macaque monkeys develop a disease very similar to humans, they have potential to provide important information in addition to small animal models. To assess the relative merits of rhesus and cynomolgus monkeys as screens for tuberculosis vaccines, we compared the efficacy of bacillus Calmette-Guérin vaccination and the course of infection in both species. Unvaccinated rhesus and cynomolgus monkeys both developed progressive disease with high levels of C-reactive protein, M. tuberculosis-specific IgG, and extensive pathology including cavitation and caseous necrosis. Bacillus Calmette-Guérin vaccination protected cynomolgus almost completely toward the development of pathology, reflected in a striking 2-log reduction in viable bacteria in the lungs compared with nonvaccinated animals. Rhesus, on the other hand, were not protected efficiently by the bacillus Calmette-Guérin. The vaccinated animals developed substantial pathology and had negligible reductions of colony-forming units in the lungs. Comparative studies in these closely related species are likely to provide insight into mechanisms involved in protection against tuberculosis.

Animals↗
PubMed2001

Long-lived immune response to early secretory antigenic target 6 in individuals who had recovered from tuberculosis.

We sought to understand the persistence and relevance of the long-lived immune response to early secretory antigenic target (ESAT-6) of Mycobacterium tuberculosis in humans. ESAT-6 is recognized by memory cells involved in protection of animals against tuberculosis (TB). Recent reports also showed that ESAT-6 response can be recovered in patients with TB and in those soon after anti-TB therapy. We chose 18 individuals who had recovered from pulmonary TB (some in remission for >5 years), and 14 bacille Calmette-Guérin-vaccinated healthy individuals for this study. The results showed that peripheral blood mononuclear cells of 10 (55.6%) of 18 patients with TB remission responded to ESAT-6 with stimulation indices >3.0, whereas none of the healthy controls responded. Functional analysis showed that 13 (72.2%) of 18 patients with TB remission produced significant amounts of IFN-gamma in response to ESAT-6, whereas only 1 (7.1%) of the 14 healthy control subjects did so. It appears that responses to ESAT-6 can persist in individuals who had recovered from pulmonary TB.

Adult↗
PubMed2001

Protective efficacy against tuberculosis of ESAT-6 secreted by a live Salmonella typhimurium vaccine carrier strain and expressed by naked DNA.

We have constructed a recombinant (r) attenuated Salmonella typhimurium strain which secretes ESAT-6 of Mycobacterium tuberculosis via the hemolysin secretion system of E. coli. Additionally, we have ligated ESAT-6 to different commercially available mammalian expression systems for use as naked DNA vaccines. We studied protection against M. tuberculosis induced by vaccination with each of these constructs alone or in combination in mice. Vaccination with a single dose of r S. typhimurium secreting ESAT-6 reduced numbers of tubercle bacilli in the lungs throughout the course of infection. The combined prime-boost vaccination did not considerably enhance protection.

Animals↗
PubMed2001

Use of ESAT-6 in the interferon-gamma test for diagnosis of bovine tuberculosis following skin testing.

The whole blood interferon-gamma (IFN-gamma) test has proven to be a practical ancillary test for re-testing cattle for bovine tuberculosis 8-28 days following tuberculin skin testing. An improvement in the specificity of the IFN-gamma test could further reduce culling of false positive animals. The primary aim of this study was to evaluate a single mycobacterial antigen, ESAT-6 in the IFN-gamma test for use in skin test-positive cattle. These skin test-positive cattle comprised 51 Mycobacterium bovis-infected animals from tuberculosis-infected herds and 85 non-infected animals from tuberculosis-free herds. The test based on ESAT-6 had a higher specificity than the test based on purified protein derivative (PPD) tuberculin, but this was offset by a small decrease in sensitivity. Use of a lower cut-off in the ESAT-6-based test improved the sensitivity, while still maintaining a very high specificity. A secondary aim in the study was to assess the ESAT-6 and PPD-based tests for detecting bovine tuberculosis in skin test-negative animals from a persistently infected herd. The PPD-based test detected the majority of the lesioned or M. bovis-culture positive animals, while the ESAT-6-based test detected a smaller proportion. The false negatives in the IFN-gamma test from both the skin test-negative and positive groups were predominantly M. bovis-culture positive animals with no visible lesions. The current study has shown that a defined specific antigen such as ESAT-6 can markedly improve the specificity of the IFN-gamma test for re-testing skin test-positive animals. An ESAT-6-based IFN-gamma test could be particularly useful to reduce the false positive rate, yet still maintain an acceptable level of sensitivity.

Animals↗
PubMed2001

Tuberculosis subunit vaccine development: on the role of interferon-gamma.

Tuberculosis (TB) remains a major global health problem and subunit vaccines for the control of the disease are presently under development. This vaccine strategy requires an in vitro correlate of protection for the identification of relevant vaccine candidate antigens and for monitoring the induction of a protective cell-mediated immune response after vaccination. New studies of experimental vaccines in the mouse model of TB support interferon-gamma as a relevant marker for the induction of a protective immune response. In contrast, searching for immunodominant antigens capable of inducing strong interferon-gamma responses in PPD positive healthy or TB infected individuals may not identify all relevant candidate antigens for inclusion in a novel TB subunit vaccine.

Animals↗
PubMed2001

Imaging brain function in humans at 7 Tesla.

This article describes experimental studies performed to demonstrate the feasibility of BOLD fMRI using echo-planar imaging (EPI) at 7 T and to characterize the BOLD response in humans at this ultrahigh magnetic field. Visual stimulation studies were performed in normal subjects using high-resolution multishot EPI sequences. Changes in R(*)(2) arising from visual stimulation were experimentally determined using fMRI measurements obtained at multiple echo times. The results obtained at 7 T were compared to those at 4 T. Experimental data indicate that fMRI can be reliably performed at 7 T and that at this field strength both the sensitivity and spatial specificity of the BOLD response are increased. This study suggests that ultrahigh field MR systems are advantageous for functional mapping in humans. Magn Reson Med 45:588-594, 2001.

Brain↗
PubMed2001

7T vs. 4T: RF power, homogeneity, and signal-to-noise comparison in head images.

Signal-to-noise ratio (SNR), RF field (B(1)), and RF power requirement for human head imaging were examined at 7T and 4T magnetic field strengths. The variation in B(1) magnitude was nearly twofold higher at 7T than at 4T ( approximately 42% compared to approximately 23%). The power required for a 90 degrees pulse in the center of the head at 7T was approximately twice that at 4T. The SNR averaged over the brain was at least 1.6 times higher at 7T compared to 4T. These experimental results were consistent with calculations performed using a human head model and Maxwell's equations. Magn Reson Med 46:24-30, 2001.

Brain↗
PubMed2001

In vivo 1H NMR spectroscopy of the human brain at 7 T.

In vivo 1H NMR spectra from the human brain were measured at 7 T. Ultrashort echo-time STEAM was used to minimize J-modulation and signal attenuation caused by the shorter T2 of metabolites. Precise adjustment of higher-order shims, which was achieved with FASTMAP, was crucial to benefit from this high magnetic field. Sensitivity improvements were evident from single-shot spectra and from the direct detection of glucose at 5.23 ppm in 8-ml volumes. The linewidth of the creatine methyl resonance was at best 9 Hz. In spite of the increased linewidth of singlet resonances at 7 T, the ability to resolve overlapping multiplets of J-coupled spin systems, such as glutamine and glutamate, was substantially increased. Characteristic spectral patterns of metabolites, e.g., myo-inositol and taurine, were discernible in the in vivo spectra, which facilitated an unambiguous signal assignment.

Adult↗
PubMed2001

Zenker's diverticulostomy with cricopharyngeal myotomy: the endoscopic approach.

BACKGROUND: The gold standard for the surgical treatment of Zenker's diverticulum is diverticulectomy and cricopharyngeal myotomy by an external approach. Unfortunately, many of the patients who present with this entity are elderly and have significant comorbidities that increase operative risk. Traditional minimally invasive approaches have not met with widespread success. However, by combining the exposure afforded by the otolaryngologist's newer bivalved operating laryngoscopes with the operative techniques made possible by the general surgeon's laparoscopic instrumentation and staplers, it is possible to achieve reliable and safe endoscopic outpatient management of this disease entity, with resumption of a normal diet on the same day. METHODS: We reviewed the physiologic basis, instrumentation, and technical considerations for this endoscopic procedure. We also documented our operative experience with 21 patients treated over an 18-month period. RESULTS: Successful minimally invasive management of Zenker's diverticulum was possible in 18 of 21 patients. In two patients, anatomic limitations of mouth and neck anatomy precluded exposure of the diverticulum; in another patient, the diverticulum was too small. Small operative perforations of the apex of the diverticulum occurred in three cases. Two of these perforations were repaired primarily with minimally invasive techniques; in the other case, treatment consisted of observation alone. In all but this last patient, oral diet was resumed on the day of the operation. Eleven of the patients were discharged from the hospital on the same day; the remaining patients went home the following morning. CONCLUSIONS: With proper patient selection, minimally invasive management of Zenker's diverticulum is a safe and effective surgical technique that allows for outpatient management of the majority of patients who present with this disease.

Cricoid Cartilage↗
PubMed2001

TB vaccines: progress and problems.

Tuberculosis (TB) is the biggest killer worldwide of any infectious disease, a situation worsened by the advent of the HIV epidemic and the emergence of multi-drug resistant strains of Mycobacterium tuberculosis. The existing vaccine, Mycobacterium bovis bacille Calmette-Guérin (BCG), has proven inefficient in several recent field trials. There is currently intense research using cutting-edge vaccine technology to combat this ancient disease. However, it is necessary to understand why BCG has failed before we can rationally develop the next generation of vaccines. Several hypotheses that might explain the failure of BCG and the strategies designed to address these shortcomings are discussed.

Animals↗
PubMed2001

Interleukin-6 regulates the phenotype of the immune response to a tuberculosis subunit vaccine.

We investigated the role of interleukin-6 (IL-6) in the development of the immune response to a subunit vaccine against tuberculosis consisting of the culture filtrate proteins of Mycobacterium tuberculosis emulsified in the adjuvant dimethyldioctadecylammonium bromide (DDA). C57Bl/6 mice immunized with this vaccine developed a strong T helper 1 (Th1) response characterized by an increased production of interferon-gamma (IFN-gamma) secreted by CD4+ T cells. Neutralization of IL-6 during in vivo priming resulted in marked reduction in the ability of T cells to secrete IFN-gamma and IL-2 and to proliferate. IL-6 gene-disrupted mice primed with the vaccine showed a decrease in the number of IFN-gamma-producing cells and an increase in IL-4-secreting cells as compared to control mice. In contrast, neutralization of IL-6 during a boost of the vaccine in previously primed mice did not affect the development of IFN-gamma-producing cells but still increased the number of IL-4-producing cells. Our work shows that IL-6 plays a major role in the priming but not in the later expression of a Th1 response to a tuberculosis vaccine.

Animals↗
PubMed2001

Failure to induce enhanced protection against tuberculosis by increasing T-cell-dependent interferon-gamma generation.

We evaluated the use of recombinant human interleukin-6 (rhIL-6) and a monoclonal antibody specific for interferon-gamma (IFN-gamma) as co-adjuvants in a subunit vaccine against tuberculosis consisting of the culture filtrate proteins of Mycobacterium tuberculosis (ST-CF) emulsified in the adjuvant dimethyl-dioctadecylammonium bromide (DDA). Both the addition of rhIL-6 and the neutralization of IFN-gamma resulted in an increased T helper type 1 (Th1) response characterized by enhanced IFN-gamma production and cell proliferation. Nevertheless, this did not result in the enhancement of protection against either an intravenous or an aerosol M. tuberculosis challenge. Our data stress the need to identify further correlates of protection in addition to IFN-gamma production to screen vaccines against tuberculosis infection.

Adjuvants, Immunologic↗
PubMed2001

Towards more accurate diagnosis of bovine tuberculosis using defined antigens.

Diagnostic accuracy is of paramount importance in test-and-slaughter programmes for the eradication of bovine tuberculosis (TB). Currently applied methods, such as in vivo skin testing and in vitro interferon-gamma (IFN- gamma) testing, utilize purified protein derivatives (PPDs), which are poorly-defined mixtures containing many individual antigenic components. It is known that false-positive responses to these reagents can occur in cattle which are not infected with TB, largely because of that antigenic complexity. This paper reviews recent approaches to the characterization of more precisely defined diagnostic tools which can be used to develop tests with greater specificity. For example, the low mass secreted protein ESAT-6 has been shown to be capable of differentiating TB-infected cattle from those which develop responsiveness to PPD through contact with environmental mycobacteria or vaccination with BCG. The information which has accumulated in recent years has shown that the increased specificity is associated with some decrease in test sensitivity, but the overall advantages of being able to make precise diagnostic decisions will have significant advantages in many situations.

Animals↗