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Biomedical subjects

A Tsai

Publications and source records attributed to A Tsai.

At least 19 recordsLinked to original sources
PubMed2006

Free amino acid and dipeptide changes in the body fluids from Alzheimer's disease subjects.

Our aim was to determine changes in free amino acid (FAA) and dipeptide (DP) concentrations in probable Alzheimer's disease (pAD) subjects compared with control (CT) subjects using liquid chromatography and electrospray ionization tandem mass spectrometry (LCMS2). We recruited gender- and age-matched study participants based on neurological and neuropsychological assessments. We measured FAAs and DPs in cerebrospinal fluid (CSF), plasma and urine using LCMS2 with selected reaction monitoring (SRM). Imidazole-containing FAAs (histidine, methyl-histidine), catecholamines (L-DOPA and dopamine), citrulline, ornithine, glycine and antioxidant DPs (carnosine and anserine) accounted for the major changes between CT and pAD. Carnosine levels were significantly lower in pAD (328.4 +/- 91.31 nmol/dl) than in CT plasma (654.23 +/- 100.61 nmol/dl). In contrast, L-DOPA levels were higher in pAD (1400.84 +/- 253.68) than CT (513.10 +/- 121.61 nmol/dl) plasma. These data underscore the importance of FAA and DP metabolism in the pathogenesis of AD. Since our data show changes in antioxidants, neurotransmitters and their precursors, or FAA associated with urea metabolism in pAD compared with CT, we propose that manipulation of these metabolic pathways may be important in preventing AD progression.

Aged↗
PubMed2004

Mutual information in coupled multi-shape model for medical image segmentation.

This paper presents extensions which improve the performance of the shape-based deformable active contour model presented earlier in [IEEE Conf. Comput. Vision Pattern Recog. 1 (2001) 463] for medical image segmentation. In contrast to that previous work, the segmentation framework that we present in this paper allows multiple shapes to be segmented simultaneously in a seamless fashion. To achieve this, multiple signed distance functions are employed as the implicit representations of the multiple shape classes within the image. A parametric model for this new representation is derived by applying principal component analysis to the collection of these multiple signed distance functions. By deriving a parametric model in this manner, we obtain a coupling between the multiple shapes within the image and hence effectively capture the co-variations among the different shapes. The parameters of the multi-shape model are then calculated to minimize a single mutual information-based cost criterion for image segmentation. The use of a single cost criterion further enhances the coupling between the multiple shapes as the deformation of any given shape depends, at all times, upon every other shape, regardless of their proximity. We found that this resulting algorithm is able to effectively utilize the co-dependencies among the different shapes to aid in the segmentation process. It is able to capture a wide range of shape variability despite being a parametric shape-model. And finally, the algorithm is robust to large amounts of additive noise. We demonstrate the utility of this segmentation framework by applying it to a medical application: the segmentation of the prostate gland, the rectum, and the internal obturator muscles for MR-guided prostate brachytherapy.

Algorithms↗
PubMed2003

Dissecting the pet18 mutation in Saccharomyces cerevisiae: HTL1 encodes a 7-kDa polypeptide that interacts with components of the RSC complex.

The yeast pet18 mutant exhibits three distinct phenotypes: temperature-sensitive lethality, failure to maintain a dsRNA virus, and respiration deficiency. We have isolated a yeast mutant, H53, with phenotypes identical to those of pet18. Based on PCR and Southern hybridization analysis, H53 was found to result from a large chromosomal deletion extending from YCR019w to YCR028c on chromosome III. Genetic analysis was carried out on H53 to correlate individual loci with each of the observed phenotypes. Disruption of YCR020c-a/MAK31 brought about a loss of dsRNA without affecting the temperature sensitive phenotype. The loss of YCR020w-b/HTL1, which encodes a hypothetical protein of 78 amino acids in length, was shown to be responsible for the temperature-sensitive lethality of the H53 mutant. Using immunoblotting, we demonstrated that a 7-kDa protein was indeed expressed in wild-type yeast, but not in a HTL1 deletion mutant. Moreover, the significance of HTL1 was investigated by isolating genes that are functionally associated with HTL1. We demonstrated that Rsc8p interacts physically with Htl1p, and that the genes RSC3, STH1 and RSC30 interact with HTL1. Thus, HTL1 may play a role in the function of the RSC complex.

Amino Acid Sequence↗
PubMed2003

Coupled multi-shape model and mutual information for medical image segmentation.

This paper presents extensions which improve the performance of the shape-based deformable active contour model presented earlier in [9]. In contrast to that work, the segmentation framework that we present in this paper allows multiple shapes to be segmented simultaneously in a seamless fashion. To achieve this, multiple signed distance functions are employed as the implicit representations of the multiple shape classes within the image. A parametric model for this new representation is derived by applying principal component analysis to the collection of these multiple signed distance functions. By deriving a parametric model in this manner, we obtain a coupling between the multiple shapes within the image and hence effectively capture the co-variations among the different shapes. The parameters of the multi-shape model are then calculated to minimize a single mutual information-based cost functional for image segmentation. The use of a single cost criterion further enhances the coupling between the multiple shapes as the deformation of any given shape depends, at all times, upon every other shape, regardless of their proximity. We demonstrate the utility of this algorithm to the segmentation of the prostate gland, the rectum, and the internal obturator muscles for MR-guided prostate brachytherapy.

Algorithms↗
PubMed2001

Flexural behaviour of post-cured composites at oral-simulating temperatures.

Post-curing treatments have been known to improve the mechanical stability of visible light-cured composites. After individual post-curing treatment, the flexural strength (FS) of four commercial direct/indirect placement composite materials which differ greatly in composition [oligocarbonate dimethacrylate (OCDMA)-based Conquest C & B (CQT), Bisphenol-A glycidyl dimethacrylate (BisGMA)-based Charisma, urethane dimethacrylate (UDMA)-based Concept (CCT), and BisGMA/UDMA-based Dentacolor] was evaluated under water in the temperature range of 12-50 degrees C. A control series was tested in air at room temperature (25 +/- 1 degrees C). Data were analysed using ANOVA and Duncan's test. Flexural strengths overall decreased (20-40%, P < 0.01) with increasing temperatures except with Conquest C & B. Surprisingly, higher FS values were found in wet conditions than in dry conditions at 25 degrees C. UDMA-based materials much more easily undergo softening in water and by temperature change than do BisGMA- or OCDMA-based materials. Post-cured composites can be significantly affected by exposure to oral environments. Different composition determines the degree of influence.

Composite Resins↗
PubMed2001

Redefining therapeutic success with virtual reality exposure therapy.

The success rate for treating phobias with in vivo exposure is high. Unfortunately, few phobics (less than 15-20%) ever seek treatment. Virtual reality (VR) exposure therapy is also proving to be highly effective. The present surveys assessed 162 students high in fear of spiders. In Study 1, when asked to choose between multisession in vivo exposure vs. multisession VR exposure therapy, 81% chose VR. In Study 2, comparing one-session in vivo versus multisession VR exposure therapy, 89% chose VR. Results suggest that VR exposure therapy may prove valuable for increasing the number of phobics who seek treatment.

Female↗
PubMed2000

Macrophage colony-stimulating factor can modulate immune responses and attract dendritic cells in vivo.

Studies have indicated that professional APCs in the periphery, such as dendritic cells and macrophages, play an important role in initiating DNA vaccine-specific immune responses. To engineer the immune response induced by DNA vaccines in vivo we investigated the modulatory effects of codelivering growth factor genes for the hematopoietic APCs along with DNA vaccines. Specifically, we examined the effects on the antigen-specific immune responses following the codelivery of the gene expression cassettes for M-CSF, G-CSF, and GM-CSF along with HIV-1 DNA immunogen constructs. We observed that coimmunization with GM-CSF increased the antibody response and resulted in a significant enhancement of lymphoproliferative response. Furthermore, among all coinjection combinations, we found that M-CSF coinjections resulted in a high level of CTL enhancement. This enhancement of CTL responses observed from the coinjection with M-CSF was CD8+ T cell dependent and was associated with the presence of CD11c+ cells at the site of injection and with the antigen-specific induction of the beta-chemokine MIP-1beta, suggesting a role for this chemokine in CTL induction. These results suggest that hematopoietic growth factors should be further studied as potential adjuvants for in vivo modulators of immune responses.

Animals↗
PubMed1999

CD86 (B7-2) can function to drive MHC-restricted antigen-specific CTL responses in vivo.

Activation of T cells requires both TCR-specific ligation by direct contact with peptide Ag-MHC complexes and coligation of the B7 family of ligands through CD28/CTLA-4 on the T cell surface. We recently reported that coadministration of CD86 cDNA along with DNA encoding HIV-1 Ags i.m. dramatically increased Ag-specific CTL responses. We investigated whether the bone marrow-derived professional APCs or muscle cells were responsible for the enhancement of CTL responses following CD86 coadministration. Accordingly, we analyzed CTL induction in bone marrow chimeras. These chimeras are capable of generating functional viral-specific CTLs against vaccinia virus and therefore represent a useful model system to study APC/T cell function in vivo. In vaccinated chimeras, we observed that only CD86 + Ag + MHC class I results in 1) detectable CTLs following in vitro restimulation, 2) detectable direct CTLs, 3) enhanced IFN-gamma production in an Ag-specific manner, and 4) dramatic tissue invasion of T cells. These results support that CD86 plays a central role in CTL induction in vivo, enabling non-bone marrow-derived cells to prime CTLs, a property previously associated solely with bone marrow-derived APCs.

Animals↗
PubMed1999

Sequence elements required for apolipoprotein B mRNA editing enhancement activity from chicken enterocytes.

Mammalian intestinal apolipoprotein B (apoB) mRNA edits codon 2153 from CAA in apoB100 mRNA to a stop codon (UAA) in apoB48 mRNA. By contrast, chicken intestinal apoB mRNA contains a CAA codon at the corresponding site, but is not edited. Chicken enterocyte S100 extracts fail to edit mammalian apoB RNA, but contain factor(s) which enhance the mammalian enterocytes editing activity. By converting the chicken apoB mooring sequences to the conserved mammalian sequences, the study confirmed that this 11-nucleotide stretch was necessary and sufficient for minimal RNA editing. Using rat and chicken apoB chimeric constructs, the study revealed that mammalian apoB sequences were required for editing enhancement. In concert with the 29-nucleotide conserved cassette, the 5' rat apoB element (nucleotides 6615-6629) increased editing at C-6666, and was necessary for editing enhancement of chicken enterocyte S100 extracts. Similarly, the 3' rat apoB element (nucleotides 6726-6752) was required for editing enhancement of chicken enterocyte S100 extracts, but to a lesser extent in efficiency, compared to the 5' region. In conclusion, this study identified the sequences required for editing enhancement activity from chicken enterocyte S100 extracts.

Animals↗
PubMed1999

Aberrant left brachiocephalic vein: CT imaging findings and embryologic correlation.

Computed tomography was utilized to evaluate aberrant left brachiocephalic vein (ALBCV), an infrequently discussed congenital vascular anomaly among Chinese people. Associated vascular variation and possible embryonic correlation are discussed. Since 1990, a total of 14 cases of ALBCV have been reported in patients receiving CT scan of chest, and was mainly an incidental diagnosis. One case was confirmed angiographically and two others were confirmed by magnetic resonance imaging. Emphasis was placed on the entry of the azygos vein into the superior vena cava (SVC), the length of the SVC, and the presence of other cardiovascular abnormalities. Of the 14 cases of ALBCV, the level of azygos vein entry was higher than the origin of the SVC in 7 cases: 4 were approximately the same level and 3 were lower. The average length of the SVC was approximately 5. 6 cm shorter than that of the general population, which is approximately 7.0 cm. Three cases had associated vascular anomaly. Most cases of ALBCV had azygos vein drainage level higher than or equal to the origin of the SVC. Right-sided aorta is one of the causes giving rise to the ALBCV during embryonic development. The CT scan remains a definitive diagnostic modality for ALBCV.

Adolescent↗
PubMed1999

Intracellular adhesion molecule-1 modulates beta-chemokines and directly costimulates T cells in vivo.

The potential roles of adhesion molecules in the expansion of T cell-mediated immune responses in the periphery were examined using DNA immunogen constructs as model antigens. We coimmunized cDNA expression cassettes encoding the adhesion molecules intracellular adhesion molecule-1 (ICAM-1), lymphocyte function associated-3 (LFA-3), and vascular cell adhesion molecule-1 (VCAM-1) along with DNA immunogens, and we analyzed the resulting antigen-specific immune responses. We observed that antigen-specific T-cell responses can be enhanced by the coexpression of DNA immunogen and adhesion molecules ICAM-1 and LFA-3. Coexpression of ICAM-1 or LFA-3 molecules along with DNA immunogens resulted in a significant enhancement of T-helper cell proliferative responses. In addition, coimmunization with pCICAM-1 (and more moderately with pCLFA-3) resulted in a dramatic enhancement of CD8-restricted cytotoxic T-lymphocyte responses. Although VCAM-1 and ICAM-1 are similar in size, VCAM-1 coimmunization did not have any measurable effect on cell-mediated responses. These results suggest that ICAM-1 and LFA-3 provide direct T-cell costimulation. These observations are further supported by the finding that coinjection with ICAM-1 dramatically enhanced the level of interferon-gamma (IFN-gamma) and beta-chemokines macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and regulated on activation normal T-cell expression and secreted (RANTES) produced by stimulated T cells. Through comparative studies, we observed that ICAM-1/LFA-1 T-cell costimulatory pathways are independent of CD86/CD28 pathways and that they may synergistically expand T-cell responses in vivo.

AIDS Vaccines↗
PubMed1999

Discrete roles for secreted and transmembrane semaphorins in neuronal growth cone guidance in vivo.

From the initial stages of axon outgrowth to the formation of a functioning synapse, neuronal growth cones continuously integrate and respond to multiple guidance cues. To investigate the role of semaphorins in the establishment of appropriate axon trajectories, we have characterized a novel secreted semaphorin in grasshopper, gSema 2a. Sema 2a is expressed in a gradient in the developing limb bud epithelium during Ti pioneer axon outgrowth. We demonstrate that Sema 2a acts as chemorepulsive guidance molecule critical for axon fasciculation and for determining both the initial direction and subsequent pathfinding events of the Ti axon projection. Interestingly, simultaneous perturbation of both secreted Sema 2a and transmembrane Sema I results in a broader range and increased incidence of abnormal Ti pioneer axon phenotypes, indicating that different semaphorin family members can provide functionally distinct guidance information to the same growth cone in vivo.

Amino Acid Sequence↗
PubMed1998

Molecular and immunological analysis of genetic prostate specific antigen (PSA) vaccine.

Nucleic acid immunization has been investigated as immunotherapy for infectious diseases as well as for treating specific types of cancers. In this approach, nucleic acid expression cassettes are directly inoculated into the host, whose transfected cells become the production source of novel and possibly immunologically foreign protein. We have developed a DNA vaccine construct which encodes for PSA by cloning a cDNA for PSA into a mammalian expression vector under control of a CMV promoter. We investigated and characterized the immunogenicity of PSA DNA expression cassettes in mice. PSA-specific immune responses induced in vivo by immunization were characterized by enzyme-linked immunosorbent assay (ELISA), T helper proliferation cytotoxic T lymphocyte (CTL), and flow cytometry assays. We observed a strong and persistent antibody response against PSA for at least 180 days following immunization. In addition, a significant T helper cell proliferation was observed against PSA protein. Using synthetic peptides spanning the PSA open frame, we identified four dominant T helper epitopes of PSA. Furthermore, immunization with PSA plasmid induced MHC Class I CD8+ T cell-restricted cytotoxic T lymphocyte response against tumor cell targets expressing PSA. The prostate represents a very specific functional organ critical for reproduction but not for the health and survival of the individual. Understanding the immunogenicity of PSA DNA immunization cassettes offers insight into the possible use of this tumor-associated antigen as a target for immunotherapy. These results demonstrate the ability of the genetic PSA to serve as a specific immune target capable of generating both humoral and cellular immune responses in vivo.

Animals↗
PubMed1998

CD8 positive T cells influence antigen-specific immune responses through the expression of chemokines.

The potential roles of CD8(+) T-cell-induced chemokines in the expansion of immune responses were examined using DNA immunogen constructs as model antigens. We coimmunized cDNA expression cassettes encoding the alpha-chemokines IL-8 and SDF-1alpha and the beta-chemokines MIP-1alpha, RANTES, and MCP-1 along with DNA immunogens and analyzed the resulting antigen-specific immune responses. In a manner more similar to the traditional immune modulatory role of CD4(+) T cells via the expression of Th1 or Th2 cytokines, CD8(+) T cells appeared to play an important role in immune expansion and effector function by producing chemokines. For instance, IL-8 was a strong inducer of CD4(+) T cells, indicated by strong T helper proliferative responses as well as an enhancement of antibody responses. MIP-1alpha had a dramatic effect on antibody responses and modulated the shift of immune responses to a Th2-type response. RANTES coimmunization enhanced the levels of antigen-specific Th1 and cytotoxic T lymphocyte (CTL) responses. Among the chemokines examined, MCP-1 was the most potent activator of CD8(+) CTL activity. The enhanced CTL results are supported by the increased expression of Th1 cytokines IFN-gamma and TNF-alpha and the reduction of IgG1/IgG2a ratio. Our results support that CD8(+) T cells may expand both humoral and cellular responses in vivo through the elaboration of specific chemokines at the peripheral site of infection during the effector stage of the immune response.

AIDS Vaccines↗
PubMed1998

Modulation of amplitude and direction of in vivo immune responses by co-administration of cytokine gene expression cassettes with DNA immunogens.

Immunization with nucleic acids has been shown to induce both antigen-specific cellular and humoral immune responses in vivo. We hypothesize that immunization with DNA could be enhanced by directing specific immune responses induced by the vaccine based on the differential correlates of protection known for a particular pathogen. Recently we and others reported that specific immune responses generated by DNA vaccine could be modulated by co-delivery of gene expression cassettes encoding for IL-12, granulocyte-macrophage colony-stimulating factor and the co-stimulatory molecule CD86. To further engineer the immune response in vivo, we investigated the induction and regulation of immune responses following the co-delivery of pro-inflammatory cytokine (IL-1 alpha, TNF-alpha, and TNF-beta), Th1 cytokine (IL-2, IL-12, IL-15, and IL-18), and Th2 cytokine (IL-4, IL-5 and IL-10) genes. We observed enhancement of antigen-specific humoral response with the co-delivery of Th2 cytokine genes IL-4, IL-5, and IL-10 as well as those of IL-2 and IL-18. A dramatic increase in antigen-specific T helper cell proliferation was seen with IL-2 and TNF-alpha gene co-injections. In addition, we observed a significant enhancement of the cytotoxic response with the co-administration of TNF-alpha and IL-15 genes with HIV-1 DNA immunogens. These increases in CTL response were both MHC class I restricted and CD8+ T cell dependent. Together with earlier reports on the utility of co-immunizing using immunologically important molecules together with DNA immunogens, we demonstrate the potential of this strategy as an important tool for the development of more rationally designed vaccines.

AIDS Vaccines↗
PubMed1998

Engineering DNA vaccines via co-delivery of co-stimulatory molecule genes.

DNA immunization has been investigated as a potential immunization strategy against infectious diseases and cancer. To enhance a DNA vaccine's ability to induce CTL response in vivo, we co-administered CD80 and CD86 expression cassettes along with HIV-1 immunogens. This manipulation resulted in a dramatic increase in MHC class I-restricted and CD8+ T-cell-dependent CTL responses in both mice and chimpanzees. This strategy of engineering vaccine producing cells to be more efficient T-cell activators could be an important tool for optimizing antigen-specific T-cell-mediated immune responses in the pursuit of more rationally designed vaccines and immune therapies.

Amino Acid Sequence↗
PubMed1998

Coadministration of IL-12 or IL-10 expression cassettes drives immune responses toward a Th1 phenotype.

Cytokines are important regulators of the immune response. They influence immune expression, the development of immunologic memory, and regulation of antigen-specific and nonspecific immune activation as well as allergic responses. In a model system in mice, we have studied the effect of plasmids expressing interleukin (IL)-10 or IL-12 on the modulation of antigen-specific responses. Coadministration of IL-12 or IL-10 genes with DNA immunogens directed the antigen-specific immune response toward a T helper (Th1)-type immunity. In addition to the modulation of antigen-specific immune responses, we studied the induction of delayed-type hypersensitivity (DTH) to contact allergens as an in vivo model of the Th1 response. We found that IL-12 and IL-10 gene-containing plasmids, and not the bacterial plasmid alone, upregulate this response. Our cytokine gene delivery technique demonstrates an important level of control of the magnitude and direction of induced immune responses and could be advantageous in a wide variety of immunotherapeutic strategies.

Animals↗