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1.
J Environ Radioact ; 84(3): 457-67, 2005.
Article in English | MEDLINE | ID: mdl-15970365

ABSTRACT

We have conducted measurements of naturally occurring radionuclides (7)Be, (210)Pb and (210)Po in air at ground level at Chilton, Oxfordshire, England. The sampling and analysis regime for the latter two isotopes has been optimised to minimise uncertainties in measurement due to decay of (210)Po and in-growth of (210)Pb during the sampling and analysis period. Analysis times were reduced by using Cerenkov counting to assay the (210)Bi daughter of (210)Pb. Monthly data collected over a four-year period are presented and discussed. (7)Be activity concentrations appear to peak in spring. (210)Pb activity concentrations also follow a seasonal trend reflecting different (222)Rn emanation rates from soil during winter and summer. Data for (210)Po show no such trend.


Subject(s)
Air Pollutants, Radioactive/analysis , Beryllium/analysis , Lead Radioisotopes/analysis , Polonium/analysis , Radioisotopes/analysis , Bismuth/analysis , England , Radiation Monitoring , Seasons
2.
J Virol ; 79(6): 3748-57, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15731268

ABSTRACT

Advances in treating and preventing AIDS depend on understanding how human immunodeficiency virus (HIV) is eliminated in vivo and on the manipulation of effective immune responses to HIV. During the development of assays quantifying the elimination of fluorescent autologous cells coated with overlapping 15-mer simian immunodeficiency virus (SIV) or HIV-1 peptides, we made a remarkable observation: the reinfusion of macaque peripheral blood mononuclear cells, or even whole blood, pulsed with SIV and/or HIV peptides generated sharply enhanced SIV- and HIV-1-specific T-cell immunity. Strong, broad CD4+- and CD8+-T-cell responses could be enhanced simultaneously against peptide pools spanning 87% of all SIV- and HIV-1-expressed proteins-highly desirable characteristics of HIV-specific immunity. De novo hepatitis C virus-specific CD4+- and CD8+-T-cell responses were generated in macaques by the same method. This simple technique holds promise for the immunotherapy of HIV and other chronic viral infections.


Subject(s)
HIV Infections/therapy , HIV/immunology , Peptides/immunology , Simian Acquired Immunodeficiency Syndrome/therapy , Simian Immunodeficiency Virus/immunology , T-Lymphocytes/immunology , Animals , Blood Component Transfusion , Blood Transfusion , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Disease Models, Animal , HIV Antigens/administration & dosage , HIV Antigens/immunology , HIV Infections/immunology , Hepatitis C/immunology , Hepatitis C Antigens/administration & dosage , Hepatitis C Antigens/immunology , Immunotherapy , Macaca nemestrina , Peptides/administration & dosage , Retroviridae Proteins/administration & dosage , Retroviridae Proteins/immunology , Simian Acquired Immunodeficiency Syndrome/immunology
3.
J Virol ; 78(24): 13819-28, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15564490

ABSTRACT

Further advances are required in understanding protection from AIDS by T-cell immunity. We analyzed a set of multigenic simian/human immunodeficiency virus (SHIV) DNA and fowlpox virus priming and boosting vaccines for immunogenicity and protective efficacy in outbred pigtail macaques. The number of vaccinations required, the effect of DNA vaccination alone, and the effect of cytokine (gamma interferon) coexpression by the fowlpox virus boost was also studied. A coordinated induction of high levels of broadly reactive CD4 and CD8 T-cell immune responses was induced by sequential DNA and fowlpox virus vaccination. The immunogenicity of regimens utilizing fowlpox virus coexpressing gamma interferon, a single DNA priming vaccination, or DNA vaccines alone was inferior. Significant control of a virulent SHIV challenge was observed despite a loss of SHIV-specific proliferating T cells. The outcome of challenge with virulent SHIV(mn229) correlated with vaccine immunogenicity except that DNA vaccination alone primed for protection almost as effectively as the DNA/fowlpox virus regimen despite negligible immunogenicity by standard assays. These studies suggest that priming of immunity with DNA and fowlpox virus vaccines could delay AIDS in humans.


Subject(s)
AIDS Vaccines/immunology , Fowlpox virus/immunology , HIV Infections/prevention & control , Immunization , Simian Acquired Immunodeficiency Syndrome/prevention & control , Vaccines, DNA/immunology , AIDS Vaccines/administration & dosage , Animals , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , HIV-1/genetics , HIV-1/immunology , Humans , Immunization Schedule , Immunization, Secondary , Interferon-gamma/immunology , Interferon-gamma/metabolism , Lymphocyte Activation , Macaca nemestrina , SAIDS Vaccines/administration & dosage , SAIDS Vaccines/immunology , Simian Immunodeficiency Virus/genetics , Simian Immunodeficiency Virus/immunology , Treatment Outcome , Vaccines, DNA/administration & dosage
4.
J Virol ; 75(23): 11930-4, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11689679

ABSTRACT

Delivering attenuated lentivirus vaccines as proviral DNA would be simple and inexpensive. Inoculation of macaques with wild-type simian immunodeficiency virus strain mac239 (SIV(mac239)) DNA or SIV(mac239) DNA containing a single deletion in the 3' nef-long terminal repeat overlap region (nef/LTR) led to sustained SIV infections and AIDS. Injection of SIV(mac239) DNA containing identical deletions in both the 5' LTR and 3' nef/LTR resulted in attenuated SIV infections and substantial protection against subsequent mucosal SIV(mac251) challenge.


Subject(s)
Simian Immunodeficiency Virus/immunology , Vaccines, DNA/administration & dosage , Viral Vaccines/administration & dosage , Amino Acid Sequence , Animals , Antibodies, Viral/biosynthesis , Base Sequence , CD4 Lymphocyte Count , DNA Primers , Interferon-gamma/biosynthesis , Macaca nemestrina , Molecular Sequence Data , Mutagenesis , Plasmids , RNA, Viral/blood , Repetitive Sequences, Nucleic Acid , Vaccines, DNA/chemistry , Vaccines, DNA/immunology , Viral Vaccines/chemistry , Viral Vaccines/immunology
5.
Aust Vet J ; 79(6): 406-8, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11491218

ABSTRACT

A number of monkey species, including African green monkeys and African vervet monkeys (Chlorocebus aethiops), are frequently infected in the wild and in captivity with a Simian immunodeficiency virus strain, SIVagm, a primate lentivirus. Up to 50% of African green monkeys are estimated to be infected with SIVagm. SIV strains are very closely related to HIV-2 strains, which are a cause of AIDS in humans, predominantly in western Africa, although cases in Australia have also been reported. It is generally thought that SIV is non-pathogenic in several natural hosts, including African green monkeys. Nevertheless many SIV strains induce a profound immunodeficiency virtually identical to HIV-1 induced AIDS in humans when administered to Asian macaque species such as rhesus (Macaca mulatta) or pigtailed macaques (M nemestrina). SIV infection of Asian macaque species is frequently employed as an animal model for AIDS vaccine studies. In November 1996 a group of 10 African vervet monkeys were imported from the USA for display at Victoria's Open Range Zoo in Werribee. Two animals in this group of monkeys later developed a fatal gastroenteric illness. These diagnoses led us to initiate SIV testing of the colony.


Subject(s)
Chlorocebus aethiops , DNA, Viral/blood , Disease Outbreaks/veterinary , Simian Acquired Immunodeficiency Syndrome/epidemiology , Simian Immunodeficiency Virus/isolation & purification , Animals , Animals, Zoo , Female , Male , Polymerase Chain Reaction/veterinary , Simian Acquired Immunodeficiency Syndrome/etiology , Simian Immunodeficiency Virus/genetics , Victoria/epidemiology
6.
J Med Primatol ; 29(3-4): 240-7, 2000 Aug.
Article in English | MEDLINE | ID: mdl-11085586

ABSTRACT

Preventive and/or therapeutic vaccines against Human Immunodeficiency Virus (HIV-1) are urgently required. Induction of cellular immunity is favoured since these responses correlate with control of HIV-1. Recombinant fowlpoxvirus (FPV) vaccines encoding both HIV-1 gag/pol and interferon-gamma (FPV gag/pol-IFNgamma) were hypothesised to enhance HIV-specific cellular immunity and were further evaluated in macaques previously infected with HIV-1. A novel assay to detect IFNgamma secretion following HIV antigen stimulation of whole blood was developed to further assess the safety and immunogenicity of the FPV gag/pol-IFNgamma vaccine. Immunisation with FPV gag/pol-IFNgamma safely enhanced HIV-specific IFNgamma secretion following ex vivo stimulation of whole blood, greater than that observed following FPV gag/pol vaccination not co-expressing IFNgamma. Both HIV-specific IFNgamma-spot-forming cells by ELISPOT and CD69 expression by CD4+ lymphocytes were also enhanced following FPV gag/pol-IFNgamma vaccination. Hence, the FPV-HIV vaccine co-expressing IFNgamma stimulated HIV-specific T cell responses in macaques, and should be further evaluated as a therapeutic or preventive HIV vaccine.


Subject(s)
AIDS Vaccines/immunology , Fowlpox virus/immunology , HIV-1/immunology , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes/immunology , Vaccines, Synthetic/immunology , AIDS Vaccines/toxicity , Animals , Antigens, CD/blood , Antigens, Differentiation, T-Lymphocyte/blood , Fowlpox virus/genetics , Genes, gag , Genes, pol , Humans , Interferon-gamma/blood , Interferon-gamma/genetics , Interferon-gamma/immunology , Lectins, C-Type , Macaca nemestrina , Safety , T-Lymphocytes, Helper-Inducer/virology , Thymidine Kinase/genetics , Time Factors , Vaccines, Synthetic/toxicity
7.
Vaccine ; 18(21): 2250-6, 2000 Apr 28.
Article in English | MEDLINE | ID: mdl-10717345

ABSTRACT

Complex recombinant fowlpoxvirus (rFPV) vaccines expressing both HIV-1 antigens and type 1 cytokines could facilitate the induction of cellular immunity against HIV-1. A single rFPV expressing both HIV-1gag/pol and human interferon-gamma (FPVgag/pol-IFNgamma) was constructed and assessed as a therapeutic vaccine for safety and immunogenicity in macaques (Macaca nemestrina) previously infected with HIV-1. FPV gag/pol-IFNgamma vaccinations were safe and enhanced T cell proliferative responses to Gag antigens (but not control tetanus antigens). Enhanced CTL responses to gag/pol antigens were also observed following IFNgamma expressing vaccinations. Since cellular immunity may be critical to controlling or preventing HIV-1 infection, these observations suggest that avipox vectors co-expressing IFNgamma should be further evaluated as therapeutic or preventive HIV-1 vaccines.


Subject(s)
AIDS Vaccines/immunology , Fowlpox virus/genetics , HIV-1/immunology , Interferon-gamma/pharmacology , Vaccines, Synthetic/immunology , Animals , DNA, Viral/analysis , HIV Antibodies/blood , Humans , Interferon-gamma/genetics , Macaca nemestrina , T-Lymphocytes, Cytotoxic/immunology , Vaccination
8.
Drugs R D ; 1(6): 431-40, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10566076

ABSTRACT

The global human immunodeficiency virus type 1 (HIV-1) epidemic is devastating many communities and a well tolerated and effective vaccine is urgently required. Several lines of evident suggest that vaccine-induced protective immunity can be achieved. This evidence includes individuals shown to have natural immunity, and the partially effective immune responses that are generated during natural infection. However, the obstacles to HIV-1 vaccine development are enormous. The only substantially effective vaccine studied in pathogenic animal models (live, attenuated vaccines) is at present far too unsafe. The only HIV-1 vaccine to proceed to efficacy trials (an envelope protein approach) has been disappointing in its immunogenicity and efficacy in preliminary trials. The antigenic variability of HIV-1 strains is also a great obstacle. Unfortunately, commercial realities also do not favour the expensive development of HIV-1 vaccines required most urgently in less developed countries. Despite these obstacles, there is cause for cautious optimism. Better tolerated HIV-1 vaccine approaches are currently showing great promise in primate models and preliminary clinical trials. Many governments and the World Bank are now providing the political will and funding necessary to fast-track HIV-1 vaccine development. Given sufficient long term scientific and commercial commitment to the HIV-1 vaccine development process, it is ultimately likely that a preventative HIV-1 vaccine will emerge.


Subject(s)
AIDS Vaccines/therapeutic use , Drugs, Investigational/therapeutic use , HIV Infections/prevention & control , HIV-1/immunology , AIDS Vaccines/immunology , HIV Infections/immunology , Humans
9.
Int J Parasitol ; 26(7): 787-91, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8894771

ABSTRACT

Investigation of restriction fragment length polymorphisms (RFLPs) associated with immunoglobulin E (IgE) and cytokine genes in the sheep genome revealed polymorphisms in the IgE constant heavy chain, interferon gamma and interleukin 4 genes. No polymorphisms were found in interleukin 1 beta or tumour necrosis factor alpha. PstI and BamHI RFLPs in the IgE gene showed differences in frequency between animals selected for resistance or susceptibility to fleece rot and blowfly strike.


Subject(s)
Cytokines/genetics , Genes, Immunoglobulin , Immunoglobulin E/genetics , Myiasis/veterinary , Polymorphism, Restriction Fragment Length , Sheep Diseases/immunology , Sheep/genetics , Animals , Disease Susceptibility , Immunity, Innate , Interferon-gamma/genetics , Interleukin-1/genetics , Interleukin-4/genetics , Male , Myiasis/immunology , Tumor Necrosis Factor-alpha/genetics
10.
J Chromatogr B Biomed Appl ; 680(1-2): 91-6, 1996 May 17.
Article in English | MEDLINE | ID: mdl-8798885

ABSTRACT

This study describes the application of aqueous two-phase partition using polyethylene glycol (PEG)-potassium phosphate systems for the direct recovery of proteins, and aggregates thereof, from mammalian brain tissue homogenates. Investigation of established methodologies for the purification of prion proteins (PrP) from bovine brain affected with transmissible spongiform encephalopathy (BSE) has identified an alternative purification regime based on aqueous two-phase partition. This circumvents energy-intensive and rate-limiting unit operations of ultracentrifugation conventionally used for isolation of PrP. Selectivity of various PEG-phosphate systems varied inversely with polymer molecular mass. The maximum protein recovery from bovine brain extracts was obtained with systems containing PEG 300. Manipulation of the aqueous environment, to back-extract protein product from the PEG-rich top phase into the phosphate-rich lower phase, enabled integration of ATPS with conventional hydrophobic interaction chromatography (HIC) which selectively removes obdurate contaminating proteins (i.e. ferritin).


Subject(s)
Brain Stem/chemistry , Phosphates/chemistry , Polyethylene Glycols/chemistry , Prions/isolation & purification , Tissue Extracts/chemistry , Water/chemistry , Animals , Cattle , Chromatography, Agarose , Electrophoresis, Polyacrylamide Gel , Ferritins/chemistry , Humans , Immune Sera/immunology , Immunoblotting , Peptides/immunology , Prion Diseases/physiopathology , Prions/immunology , Spectrophotometry, Ultraviolet
11.
J Res Natl Inst Stand Technol ; 99(4): 485-494, 1994.
Article in English | MEDLINE | ID: mdl-37405298

ABSTRACT

Calculations of the first and second moments of displacement damage energy distributions from clastic collisions and from nuclear reactions, at proton energies ranging from 10 MeV to 300 MeV, are incorporated into a model describing the probability of damage as a function of the proton fluence and the size of the sensitive micro-volume in Si. Comparisons between the predicted and measured leakage currents in Si imaging arrays illustrate how the Poisson distribution of higher energy nuclear reaction recoils affects the pixel-to-pixel variance in the damage across the array for proton exposures equivalent to mission duration of a few years within the earth's trapped proton belts. Extreme value statistics (EVS) quantify the largest expected damage extremes following a given proton fluence, and an analysis derived from the first-principle damage calculations shows excellent agreement with the measured extremes. EVS is also used to demonstrate the presence of high dark current pixels, or "spikes," which occur from different mechanisms. Different sources of spikes were seen in two different imager designs.

12.
Health People ; 8(1): 1, 1974 Mar.
Article in English | MEDLINE | ID: mdl-4496483
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