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Research Interests: Chemistry, Organic Chemistry, Structure, Atomic Force Microscopy, SEM, and 11 moreModel, Glucose, AFM, MPI, TEM, Fructose, Food Sciences, Microspheres, Inulin, L, and Carbohydrate Polymers
Abstract Low doses of actinomycin D (0.1 μg/ml) can enhance, markedly inhibit, or have no effect on poliovirus growth: the outcome depends on the pretreatment given the cells, in particular on the properties of the serum in which they... more
Abstract Low doses of actinomycin D (0.1 μg/ml) can enhance, markedly inhibit, or have no effect on poliovirus growth: the outcome depends on the pretreatment given the cells, in particular on the properties of the serum in which they have been incubated. Preincubation of cells without serum or with certain batches of calf serum renders subsequent virus growth sensitive to actinomycin. It appears that some sera contain a specific substance that induces an actinomycin-resistant state; this substance is probably insulin, since physiological levels of insulin are shown to simulate active batches of serum. Other hormones are inactive. In sensitive cells, actinomycin prevents synthesis of viral RNA by affecting a stage of growth that occurs after penetration; this stage is a fairly late one. Cells in the actinomycin-sensitive state do not necessarily differ from actinomycin-resistant cells in microscopical appearance, rate of multiplication, rates of incorporation of radioactive leucine and uridine, and yield of virus in absence of actinomycin.
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... The damage by urea culminates in 1 Present address: Department of Microbiology, John Curtin School of Medical Research, Aus tralian National University, Canberra, Australia. ... Virology 2, 665678. STAKK, GR, STEIN, WH, and MOORE, S.... more
... The damage by urea culminates in 1 Present address: Department of Microbiology, John Curtin School of Medical Research, Aus tralian National University, Canberra, Australia. ... Virology 2, 665678. STAKK, GR, STEIN, WH, and MOORE, S. (1960). ...
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Research Interests: Chemistry, Gamma Rays, Medicine, Biological Sciences, Mice, and 13 moreFemale, Animals, Ri, Vaccine, Sterilization, Bp, Gi, PBS, Gr, Protein isoforms, Inulin, Adjuvant, and Medical and Health Sciences
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Summary A count of specifically labelled tryptic peptides from purified poliovirus (strain Mahoney) showed that the amino acid sequence comprising its structural protein contains at least 21 and 25 uniquely placed residues of histidine... more
Summary A count of specifically labelled tryptic peptides from purified poliovirus (strain Mahoney) showed that the amino acid sequence comprising its structural protein contains at least 21 and 25 uniquely placed residues of histidine and methionine, respectively. Amino acid analysis after performic acid oxidation showed a content of, respectively, 21 and 27 moles of these residues per 1000 amino acids recovered. Accordingly, poliovirus structural protein must comprise a unique sequence of about 1000 amino acids, representing about 40% of the coding potential of the poliovirus genome. The correspondence of this percentage with the proportion of the poliovirus genetic map occupied by structural protein genes (48%) suggests that the map represents a major part of the genome. A value of about 1000 amino acids, or 100 to 110000 daltons of protein, for the repeating structural unit, coupled with a total content of 6.0 to 6.4 × 106 daltons of protein in the poliovirus particle, indicates that it contains 60 such structural units and that its triangulation number = 1.
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Summary A count of specifically labelled tryptic peptides from purified poliovirus (strain Mahoney) showed that the amino acid sequence comprising its structural protein contains at least 21 and 25 uniquely placed residues of histidine... more
Summary A count of specifically labelled tryptic peptides from purified poliovirus (strain Mahoney) showed that the amino acid sequence comprising its structural protein contains at least 21 and 25 uniquely placed residues of histidine and methionine, respectively. Amino acid analysis after performic acid oxidation showed a content of, respectively, 21 and 27 moles of these residues per 1000 amino acids recovered. Accordingly, poliovirus structural protein must comprise a unique sequence of about 1000 amino acids, representing about 40% of the coding potential of the poliovirus genome. The correspondence of this percentage with the proportion of the poliovirus genetic map occupied by structural protein genes (48%) suggests that the map represents a major part of the genome. A value of about 1000 amino acids, or 100 to 110000 daltons of protein, for the repeating structural unit, coupled with a total content of 6.0 to 6.4 × 106 daltons of protein in the poliovirus particle, indicates that it contains 60 such structural units and that its triangulation number = 1.
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When primary baby mouse skin (BMS) cultures were subcultured for 48 hours into media containing 10(-6) to 10(-7) M colchicine or demecolcine, the number of altered cell foci appearing after 3-4 weeks' maintenance at 36 degrees C... more
When primary baby mouse skin (BMS) cultures were subcultured for 48 hours into media containing 10(-6) to 10(-7) M colchicine or demecolcine, the number of altered cell foci appearing after 3-4 weeks' maintenance at 36 degrees C was substantially enhanced over drug-free controls. This applied whether or not the primary cultures had been irradiated with white fluorescent light. The additional presence of cytochalasin D and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) sometimes improved and sometimes partly suppressed the enhancing effect of the antitubulin drugs, and these drugs were omitted for reproducible focus enhancement. The enhancement depended on passage through DNA synthesis in presence of colchicine, which did not prevent concurrent or subsequent DNA synthesis but induced a substantial proportion (greater than 33%) to replicate in the tetraploid (4n to 8n) chromosome configuration. Another effect was to induce widespread asymmetric nuclear division, allowing the potential for chromosome loss. All these effects occurred within the first one or few cell cycles after removal of the antitubulin drugs. The results suggest that the generation of tetraploidy perhaps followed by chromosome loss may be an important factor in the rapid induction of altered cell foci. Pre-existing DNA damage is another important factor.
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Algammulin is a new vaccine adjuvant comprising a stable suspension of 1-2 microns ovoids of the immune stimulant gamma inulin in which alum (Alhydrogel) is embedded as a protein carrier. Adjuvanticity tests in mice with Algammulin show... more
Algammulin is a new vaccine adjuvant comprising a stable suspension of 1-2 microns ovoids of the immune stimulant gamma inulin in which alum (Alhydrogel) is embedded as a protein carrier. Adjuvanticity tests in mice with Algammulin show that the presence of gamma inulin on the alum particles has synergistically enhanced their adjuvanticity for low doses of hepatitis B surface antigen. The primary-response titres of HBsAg-specific antibody from a given low dose of alum injected as Algammulin were 3- to 5.6-fold greater than those from the same alum dose injected as free alum. This corresponds closely with more extensive previous work using keyhole limpet haemocyanin as antigen.
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There has been a recent resurgence of interest into new and improved vaccine adjuvants. This interest has been stimulated by the need for new vaccines to combat problematic pathogens such as SARS and HIV, and to counter potential... more
There has been a recent resurgence of interest into new and improved vaccine adjuvants. This interest has been stimulated by the need for new vaccines to combat problematic pathogens such as SARS and HIV, and to counter potential bioterrorist attacks. A major bottleneck in vaccine development is the low immunogenicity of purified subunit or recombinant proteins, creating the need for safe human adjuvants with high potency. A major problem in the search for the ideal adjuvant is that adjuvants that promote cell-mediated (Th1) immunity (e.g. Freund's complete adjuvant) generally have unacceptable local or systemic toxicity that precludes their use in human vaccines. There is a need for a safe, non-toxic adjuvant that is able to stimulate both cell-mediated and humoral immunity. Inulin-derived adjuvants that principally stimulate the innate immune system through their ability to activate the alternative complement pathway have proven ability to induce both cellular and humoral immunity. With their excellent tolerability, long shelf-life, low cost and easy manufacture, they offer great potential for use in a broad range of prophylactic and therapeutic vaccines. Based on successful animal studies in a broad range of species, human trials are about to get underway to validate the use of inulin-based adjuvants in prophylactic vaccines against hepatitis B, malaria and other pathogens. If such trials are successful, then it is possible that inulin-derived adjuvants will one day replace alum as the adjuvant of choice in most human prophylactic vaccines.
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The role for adjuvants in human vaccines has been a matter of vigorous scientific debate, with the field hindered by the fact that for over 80 years, aluminum salts were the only adjuvants approved for human use. To this day, alum-based... more
The role for adjuvants in human vaccines has been a matter of vigorous scientific debate, with the field hindered by the fact that for over 80 years, aluminum salts were the only adjuvants approved for human use. To this day, alum-based adjuvants, alone or combined with additional immune activators, remain the only adjuvants approved for use in the USA. This situation has not been helped by the fact that the mechanism of action of most adjuvants has been poorly understood. A relative lack of resources and funding for adjuvant development has only helped to maintain alum's relative monopoly. To seriously challenge alum's supremacy a new adjuvant has many major hurdles to overcome, not least being alum's simplicity, tolerability, safety record and minimal cost. Carbohydrate structures play critical roles in immune system function and carbohydrates also have the virtue of a strong safety and tolerability record. A number of carbohydrate compounds from plant, bacterial, yeast and synthetic sources have emerged as promising vaccine adjuvant candidates. Carbohydrates are readily biodegradable and therefore unlikely to cause problems of long-term tissue deposits seen with alum adjuvants. Above all, the Holy Grail of human adjuvant development is to identify a compound that combines potent vaccine enhancement with maximum tolerability and safety. This has proved to be a tough challenge for many adjuvant contenders. Nevertheless, carbohydrate-based compounds have many favorable properties that could place them in a unique position to challenge alum's monopoly over human vaccine usage.
Research Interests: Vaccines, Biology, Medicine, Humans, United States, and 8 moreBacteria, Plants, Clinical Sciences, Immune system, CARBOHYDRATES, Yeasts, Glycomics, and Adjuvant
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Mesenchymal cells from primary BMS (baby mouse skin) cultures formed secondary monolayers subject to density-dependent inhibition. The monolayers remained quiescent but in good condition for 6-8 weeks if given weekly medium changes.... more
Mesenchymal cells from primary BMS (baby mouse skin) cultures formed secondary monolayers subject to density-dependent inhibition. The monolayers remained quiescent but in good condition for 6-8 weeks if given weekly medium changes. Exposure of the primary cultures to fluorescent light and/or oxygen produced "altered" cells that gave rise in the secondary cultures to foci of up to 10(4) cells after 15 days. These foci overgrew the background BMS cells. The rate of growth, morphology, and arrangement of the altered cells varied greatly between foci but much less within a focus, which usually showed one or more characters of neoplastic cells. The initiation of foci was apparently not transmissible by an infectious agent.
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alpha-D-glucopyranosyl-[beta-D-fructofuranosyl](n-1)-D-fructofuranoside, commonly referred to as inulin, is a natural plant-derived polysaccharide with a diverse range of food and pharmaceuticalapplications. It is used by the food... more
alpha-D-glucopyranosyl-[beta-D-fructofuranosyl](n-1)-D-fructofuranoside, commonly referred to as inulin, is a natural plant-derived polysaccharide with a diverse range of food and pharmaceuticalapplications. It is used by the food industry as a soluble dietary fibre and fat or sugar replacement, and in the pharmaceutical industry as a stabiliser and excipient. It can also be used as a precursor in the synthesis of a wide range of compounds. New uses for inulin are constantly being discovered, with recent research into its use for slow-release drug delivery. Inulin, when in a particulate form, possesses anti-cancer and immune enhancing properties. Given its increasing importance to industry, this review explains how inulin's unique physico-chemical properties bestow it with manyuseful pharmaceutical applications.
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Research Interests: Chemical Engineering, Materials Science, Organic Chemistry, Molecular Dynamics Simulation, Small angle X-ray and neutron scattering, and 10 moreTransmission Electron Microscopy, Medicine, Polymer, Computer Simulation, Crystallinity, X ray diffraction, Fourier transform infrared spectroscopy, Food Sciences, Inulin, and Carbohydrate Polymers
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Research Interests: Chemistry, Organic Chemistry, Crystallization, Medicine, MPI, and 10 moreRi, Fructose, Bp, Gi, PBS, FRM, Food Sciences, Inulin, Carbohydrate Polymers, and stereoisomerism
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The adjuvant effect of γ‐inulin, a strong activator of the alternative complement pathway, is well‐known, but its exact mechanism is not revealed yet. Here, we show that macrophages, isolated from the peritoneal cavity of... more
The adjuvant effect of γ‐inulin, a strong activator of the alternative complement pathway, is well‐known, but its exact mechanism is not revealed yet. Here, we show that macrophages, isolated from the peritoneal cavity of γ‐inulin‐injected mice and used as antigen‐presenting cells, enhance the proliferation of antigen‐specific T‐cells up to 2.5‐fold when compared with macrophages of nontreated animals. This effect is abrogated by the presence of anti‐C3 F(ab′)2 fragments and by prior decomplementation of the donor animals with CVF. It is demonstrated that treatment of mice with the adjuvant results in deposition of C3‐fragments onto the surface of peritoneal macrophages, as does in vitro incubation of the cells with γ‐inulin in the presence of fresh autologous serum. Prior incubation of macrophages with γ‐inulin plus serum in vitro enhances subsequent C3 production. Because it has been shown earlier that CR1/2 expressed on activated T‐cells and interacting with covalently bound C3‐f...
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Activation of the APC is pointed out as the common factor in all sufficiently studied cancer treatments employing nonspecific, active immunotherapy. This chapter outlines the molecular biology of both APC and classical pathway of... more
Activation of the APC is pointed out as the common factor in all sufficiently studied cancer treatments employing nonspecific, active immunotherapy. This chapter outlines the molecular biology of both APC and classical pathway of complement, summarizes the alternative pathway's biologic activities especially in relation to the C3/C5 convertase C3b,Bb, and its implications in the mechanism of host defense against malignancies, particularly relating to the activated macrophage. The many involvements of the APC in the various agents used for nonspecific active immunotherapy are reviewed, and possible clinical implications outlined. It is concluded that activation of the APC can be proposed as the specific theoretical basis so far lacking for this treatment modality and that it is accordingly feasible to attempt to monitor clinical application of this principle by fine-tuning of APC activation in cases of human cancer.
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The study reported in this article addressed the potential safety impact of consumer movement toward smaller vehicle choices by examining the makeup of the full British Columbia (BC) vehicle fleet--from smaller cars to heavy commercial... more
The study reported in this article addressed the potential safety impact of consumer movement toward smaller vehicle choices by examining the makeup of the full British Columbia (BC) vehicle fleet--from smaller cars to heavy commercial vehicles. The basic assumption made was that some operators of heavy light trucks/vans (LTVs) or sport utility vehicles (SUVs) would, in the short term, be induced to downsize to lighter vehicles of the same type. The 2000-2007 BC crash-claim data at the Insurance Corporation of British Columbia (ICBC) was used to create matrices of average information by culpable and nonculpable entities in two-vehicle collisions in 15 weight categories. Models for the effects of various driver/crash characteristics on injury potential were created and used to adjust the effect calculated solely on the basis of weight change. Levels of heavy LTV/SUV replacement from 0.05 to 0.95 of the current population were tested and the redistribution of vehicles was done in such a way that the relationship between small-large vehicle injury ratio and large-small vehicle mass ratio over the whole fleet remained constant as did the relative proportions of culpable and nonculpable involvements. The net effect of downsizing in the manner assumed for this study was mildly positive in terms of overall injury risk--that is, downsizing resulted in slightly fewer total injuries--but not in the case of fatalities, which tended to be increased by a more substantial margin. However, the results showed that even replacing substantial proportions of the heavy LTV/SUV population would not result in a large impact on safety. Replacing almost all the heavy LTV/SUVs with lighter versions should reduce injuries by less than 1 percent and increase fatalities by 3.5 percent percent. Nevertheless, in terms of persons impacted and the associated costs, the effects would be noticeable. The issue for policy-makers is to judge how the environmental benefits associated with encouraging such change compare with the net costs in terms of safety outcomes.