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In this paper different floating oscillator models for describing the amide I band of peptides and proteins are compared with density functional theory (DFT) calculations. Models for the variation of the frequency shifts of the os...
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In this paper different floating oscillator models for describing the amide I band of peptides and proteins are compared with density functional theory (DFT) calculations. Models for the variation of the frequency shifts of the oscillators and the nearest-neighbor coupling between them with respect to conformation are constructed from DFT normal mode calculations on N-acetyl-glycine-N-'-methylamide. The calculated frequencies are compared with those obtained from existing electrostatic models. Furthermore, a new transition charge coupling model is presented. We suggest a model which combines the nearest-neighbor maps with long-range interactions accounted for using the new transition charge model and an existing electrostatic map for long-range interaction frequency shifts. This model and others, which account for the frequency shifts by electrostatic maps exclusively, are tested by comparing the predicted IR spectra with those from DFT calculations on the pentapeptide [Leu]-enkephalin. The new model described above gives the best agreement and, after a systematic blueshift is accounted for, reproduces the DFT frequencies to within 3.5 cm(-1). The correlation of the intensities for this model with intensities from DFT calculations is 0.94. (c) 2006 American Institute of Physics.
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The unique antigenic determinants (idiotype (Id)) of the immunoglobulin secreted by myeloma tumor can serve as a tumor-specific antigen for active immunotherapy. Our objective was to induce tumor-specific T-cell immunity in bone m...
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The unique antigenic determinants (idiotype (Id)) of the immunoglobulin secreted by myeloma tumor can serve as a tumor-specific antigen for active immunotherapy. Our objective was to induce tumor-specific T-cell immunity in bone marrow transplant (BMT) donors to enhance antitumor effects of allografts. We vaccinated five HLA-matched sibling donors with myeloma Id proteins isolated from recipient plasma before bone marrow harvest. Recipients were administered booster Id immunizations following transplantation. Vaccination induced donor Id and carrier-specific cellular and/or humoral immune responses. Two recipients died within 30 days of BMT from transplant-related complications. Id and carrier-specific T-cell responses were detected in all three remaining patients post-, but not pre-BMT and persisted for 18 months. All three surviving patients converted from partial to complete responses following BMT. Two of the three patients remain disease-free 7 years and 8 years after BMT, and the third died of renal failure after 5.5 years while in complete remission from myeloma. Our results suggest that myeloma Id vaccination induces specific T-cell immunity in healthy donors which may be transferable by BMT, is associated with prolonged disease-free survival of recipients, and may represent a general strategy to enhance graft-versus-tumor effect in other malignancies for which defined tumor-specific antigens exist.
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Clara cell secretory protein (CCSP) is one of the most abundant proteins present in airway lining fluid of mammals. In an effort to elucidate the function of CCSP, we established CCSP-null [CCSP(-/-)] mice and demonstrated altered...
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Clara cell secretory protein (CCSP) is one of the most abundant proteins present in airway lining fluid of mammals. In an effort to elucidate the function of CCSP, we established CCSP-null [CCSP(-/-)] mice and demonstrated altered sensitivity to various environmental agents including oxidant pollutants and microorganisms. Although CCSP deficiency itself may be central to the observed changes in environmental susceptibility, altered lung gene expression associated with CCSP deficiency may contribute to the observed phenotype. To determine whether CCSP deficiency results in altered lung gene expression, high-density cDNA microarrays were used to profile gene expression in the total lung RNA of wild-type and CCSP(-/-) mice. Genes that were differentially expressed between wild-type and CCSP(-/-) mice included a previously non-annotated expressed sequence tag (EST W82219) and immunoglobulin A (IgA), both of which were elevated with CCSP deficiency. mRNA expression of EST W82219 and IgA was localized in thelungs of wild-type and CCSP(-/-) mice to airway Clara cells and peribronchial lymphoid tissues, respectively. We conclude that CCSP deficiency is associated with 1) altered gene expression in Clara cells of the conducting airway epithelium and 2) alterations to peribronchial B lymphocytes. These findings identify new roles for Clara cells and their secretions in airway homeostasis.
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BACKGROUND: The objective of this study was to evaluate needle and syringe program (NSP) policies and procedures before and after the dissemination of a set of best practice recommendations. METHODS: An on-line survey of 32 core N...
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BACKGROUND: The objective of this study was to evaluate needle and syringe program (NSP) policies and procedures before and after the dissemination of a set of best practice recommendations. METHODS: An on-line survey of 32 core NSP managers (100% response rate) and 62 satellite NSP managers (63% response rate). The survey included items about the distribution of needles/syringes, other injection-related equipment and inhalation equipment, and use of a best practice recommendations document. RESULTS: The majority of NSPs reported following needle and syringe best practice recommendations. Most core NSPs (88%, n=28) and satellite NSPs (84%, n=52) distributed cookers following the dissemination of the document. All core NSPs (100%, n=32) and nearly all satellite NSPs (97%, n=60) distributed sterile water ampoules in 2008, many more than in 2006. Although more NSPs distributed safer inhalation equipment in 2008, the majority did not distribute these items. More satellite NSPs (44%, n=27) distributed glass stems than the core NSPs (16%, n=5). Commonly cited implementation barriers included funding, senior management and decision-making. CONCLUSION: Our findings demonstrate that NSPs will implement empirically based best practice recommendations and welcome such guidance. The managers we surveyed not only reported increased implementation of practices that have been empirically shown to help reduce disease transmission among injection drug users (IDUs), they also used the best practices document for additional purposes, such as planning and advocacy, and expressed interest in having sets of recommendations developed for other areas of harm reduction. Ensuring high-quality and consistent NSP services is essential to prevent transmission of HIV among people who inject drugs and others in the community. Best practice recommendations can assist in achieving these goals.
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Aedes notoscriptus colonized from Brisbane, Queensland, Australia, were fed on blood suspensions containing either Barmah Forest (BF) virus, dengue virus type 1 (DEN-1), dengue virus type 2 (DEN-2), dengue virus type 3 (DEN-3), or...
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Aedes notoscriptus colonized from Brisbane, Queensland, Australia, were fed on blood suspensions containing either Barmah Forest (BF) virus, dengue virus type 1 (DEN-1), dengue virus type 2 (DEN-2), dengue virus type 3 (DEN-3), or dengue virus type4 (DEN-4). A. notoscriptus was shown to be moderately susceptible to oral infection with BF virus, ID50=103.3 CCID50 per mosquito, with titres in infected mosquitoes peaking 10 days after infection. BF virus transmission occurred between days 5 and 12, with an average rate of 45% (range, 40-50%). For DEN 1-4, A. notoscriptus showed low level susceptibility to oral infection, with maximum head and thorax squash infection rates of 8, 5, 13 and 3%, respectively. Rates of infection were notably higher in anorth Queensland strain of A. aegypti used as a positive control, with maximum thorax squash infection rates of 58, 68, 78 and 60% for DEN 1-4, respectively. On the basis of these data, it is concluded that A. notoscriptus could act as an efficient vector of BF in urban environments, but it is unlikely to be an important vector of DEN.
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Lymphomas express a tumor-specific antigen which can be targeted by cancer vaccination. We evaluated the ability of a new idiotype protein vaccine formulation to eradicate residual t(14;18)+ lymphoma cells in 20 patients in a homo...
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Lymphomas express a tumor-specific antigen which can be targeted by cancer vaccination. We evaluated the ability of a new idiotype protein vaccine formulation to eradicate residual t(14;18)+ lymphoma cells in 20 patients in a homogeneous, chemotherapy-induced first clinical complete remission. All 11 patients with detectable translocations in their primary tumors had cells from the malignant clone detectable in their blood by PCR both at diagnosis and after chemotherapy, despite being in complete remission. However, 8 of 11 patients converted to lacking cells in their blood from the malignant clone detectable by PCR after vaccination and sustained their molecular remissions. Tumor-specific cytotoxic CD8+ and CD4+ T cells were uniformly found (19 of 20 patients), whereas antibodies were detected, but apparently were not required for molecular remission. Vaccination was thus associated with clearance of residual tumor cells from blood and long-term disease-free survival. The demonstration of molecular remissions, analysis of cytotoxic T lymphocytes against autologous tumor targets, and addition of granulocyte-monocyte colony-stimulating factor to the vaccine formulation provide principles relevant to the design of future clinical trials of other cancer vaccines administered in a minimal residual disease setting.
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Laboratory bioassay studies were conducted in southeast Queensland, Australia, on the efficacy of Teknar, VectoBac 12AS, and Cybate (active ingredient: 1,200 international toxic units Bacillus thuringiensis var. israelensis [Bti])...
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Laboratory bioassay studies were conducted in southeast Queensland, Australia, on the efficacy of Teknar, VectoBac 12AS, and Cybate (active ingredient: 1,200 international toxic units Bacillus thuringiensis var. israelensis [Bti]) against 3rd instars of the arbovirus vectors Aedes aegypti, Ae. notoscriptus, Ae. vigilax, and Ae. camptorhynchus. Probit analyses were then used to determine LD50 (median lethal dose), LD50, and lethal dose ratios (LDR). Aedes aegypti and Ae. notoscriptus, both container-habitat species, tolerated the highest Bti concentrations compared with saltmarsh Ae. vigilax and Ae. camptorhynchus. For example, the LDR for Ae. vigilax versus Ae. notoscriptus exposed to Cybate was 0.14 (95% confidence limit [CL] 0.03-0.61). Similarly, the Cybate LDR for Ae. camptorhynchus versus Ae. notoscriptus was 0.22 (95% CL 0.07-0.70). Teknar produced similar results with an LDR of 0.21 (95% CL 0.04-1.10) for Aedes vigilax versus Aedes notoscriptus. Differences in product efficacy were found when tested against the 2 container-breeding species. Cybate was less effective than Teknar with LDRs of 1.55 (95% CL 0.65-3.67) and 1.87 (95% CL 0.68-5.15) for Aedes aegypti and Ae. notoscriptus, respectively. The significant differences in susceptibility between mosquito species and varying efficacy between products highlight the importance of evaluating concentration-response data prior to contracting with distributors of mosquito control products. This information is crucial to resistance management strategies.
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