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Biomedical subjects

R G Olsen

Publications and source records attributed to R G Olsen.

At least 19 recordsLinked to original sources

Specific absorption rate and radiofrequency current-to-ground in human models exposed to near-field irradiation.

To expand our knowledge of near-field radiofrequency energy absorption in occupationally exposed workers, we used coffin-sized calorimeters to measure specific absorption rate in full-size human models. The models were subjected to near-field irradiation at two frequencies at an outdoor groundplane facility. We also measured radiofrequency current-to-ground in the models to supplement a previous study at 29.9000 MHz. The results have enabled us to construct a frequency-independent mathematical relationship between specific absorption rate and radiofrequency current for the given exposure system. Moreover, the results show a favorable comparison to radiofrequency radiation dosimetry handbook predictions of average specific absorption rate when only the vertical electric field (E-field) component is used to normalize specific absorption rate. Once determined on a case-by-case basis, the use of specific absorption rate vs. radiofrequency current curves for any exposure system or condition could be a simple and quick method to determine onsite compliance with specific absorption rate-based exposure standards.

Absorption↗

Chronic feline leukemia virus infection alters arachidonic acid proportions in vivo and in vitro.

The polyunsaturated omega-6 fatty acid, arachidonic acid ([AA] 20:4n-6), is both the key of the immunoregulatory substances, prostaglandins, and leukotrienes, and an essential component of immune cell membrane phospholipids, providing stability and flexibility to ensure cellular function. To explore possible effects of the physiological burden of viral replication in chronic viral infections on AA availability, plasma total esterified fatty acid (FA) proportions were measured in the feline leukemia (FeLV) model. Plasma FA profiles of 12 specific-pathogen-free cats with chronic infections with Rickard strain feline leukemia virus (FeLV-R) were compared with 12 age- and sex-matched uninfected specific-pathogen-free cats at 4 months after infection. A significant decrease from normal of average AA proportion was found in FeLV-R-infected cat plasma, while other major FA (palmitic, stearic, and oleic and omega-3 FA normally remained present until near death. Since plasma FA content rapidly affects circulating immune cell membrane composition and since FeLV infection also targets immune cells, we compared FA profiles of feline T4-thymic lymphoma 3201 cell membranes that were infected with virulent FeLV-R or less virulent FeLV-A, at 20 days after viral inoculation with sham-inoculated uninfected 3201 cells. Significantly altered FA proportions and ratios of saturated to unsaturated FA found in infected cell membranes were similar to plasma FA changes and paralleled the virulence of the FeLV inoculum. Altered postinfection FA proportions may impart serious functional defects to the immune cells of chronic FeLV-infected cats, contributing to the inability of their immune systems to eliminate FeLV by depleted plasma AA stores and modified cell membrane composition. Decreased AA availability may be an important factor in the cachexia and fatal outcome of FeLV infection.

Animals↗

Fusion activity dissociated from replication ability in feline immunodeficiency virus (FIV) in human cells.

Multinucleated-giant-cell formation followed by cell killing was observed after cocultivation of the feline immunodeficiency virus (FIV)-producing feline T-cell line 3201/FIV with various human cells, including T-cell lines carrying human T-cell lymphotropic virus type I (HTLV-I). The susceptibility to giant cell formation varied with the cell lines tested. Cocultivation of irradiated 3201/FIV cells with MT-2 cells resulted in giant cell formation as early as 2 h in culture, with striking resemblance to that induced by human immunodeficiency virus (HIV). MT-4 cells (HTLV-I positive) and H9 cells (HTLV-I negative) were less susceptible than MT-2 to the induction of syncytia. MOLT-4 cells (HTLV-I negative) had intermediate sensitivity to syncytia formation. No syncytia were observed in the monocytic cell line U-937 (HTLV-I negative). Syncytia formation between 3201/FIV and MT-2 cells was inhibited by polyclonal cat anti-FIV antisera but not polyclonal cat anti-feline leukemia virus (FeLV) antisera, goat anti-FeLV, uninfected specific-pathogen-free cat serum, human anti-HTLV-I antisera, or normal human and goat serum. Concentrated cell-free FIV supernatant from 3201/FIV also induced giant cells of MT-2 cells that were indistinguishable from those induced by cocultivation. Giant cells and extensive cell killing associated with giant cell formation declined and disappeared within 10 days. Surviving cells appeared to be of normal size and grew continuously without expressing FIV antigen or releasing infective virus. Although Southern blot analysis using probes specific for FIV could not detect proviral DNA in any of the five human cell lines cocultured with irradiated 3201/FIV cells, the polymerase chain reaction (PCR) technique detected FIV-specific DNA in MOLT-4 cells. DNA from the FIV-PCR positive MOLT-4 cells was PCR negative for endogenous FeLV-specific sequences, indicating that the MOLT-4 cell DNA was not contaminated with DNA from feline cells (i.e., 3201 cells). The FIV-MOLT-4 cells remained PCR positive for FIV after 40 passages, suggesting stable integration in the human cell line. These findings indicate that FIV is capable of forming proviral DNA in human T-lymphoid cells by cocultivation, although this FIV-carrying human cell line failed to produce replication-competent viruses.

Animals↗

Anti-human immunodeficiency virus (HIV) agents are also potent and selective inhibitors of feline immunodeficiency virus (FIV)-induced cytopathic effect: development of a new method for screening of anti-FIV substances in vitro.

The ability of several known anti-HIV substances to inhibit feline immunodeficiency virus (FIV) was tested. The results showed that FIV infection of feline T-cells was almost completely blocked in the presence of all of the agents tested. However, FIV-induced syncytium formation between a human T-cell line (MT-2 cells) and a FIV-infected feline lymphocyte cell line (3201/FIV) was inhibited only by dextran sulfate and pradimicin A. The assay used to measure syncytium inhibition was rapid and did not use potentially hazardous human immunodeficiency virus (HIV)-infected cells. The efficacy results coincided with those of HIV studies.

Animals↗

Effect of 1,1-dimethylhydrazine (UDMH) on Corynebacterium parvum-associated immunosuppression in mice.

These studies further investigate the immunoenhancement properties of UDMH by utilizing Corynebacterium parvum-induced immunosuppressed mice as well as evaluating activated macrophage production of reactive oxygen intermediates or their effects. Forty-eight hour Con A-induced lymphoblastogenic responses from splenocytes isolated from C. parvum and UDMH-treated Balb/C mice were significantly increased compared with C. parvum alone, although less than normal control mice (no treatment). In vitro bioassay of IL-2 production in cell culture supernatant isolated from these same treatment groups exhibited a pattern of stimulation similar to that of lymphocyte blastogenesis. In addition, UDMH did not interfere with H2O2-mediated suppression of either Con A- or LPS-induced lymphocyte blastogenesis and actually enhanced suppression of Con A-induced lymphocyte cultures at 25 micrograms/ml. We also report that production of superoxide anion from TPA-activated peritoneal macrophages exposed to various concentrations of UDMH in vitro was not affected. Although in vivo exposure to UDMH partially reversed C. parvum-induced immunosuppression in mice, the exact mechanism by which UDMH acts to reverse this immune suppression is not clear. UDMH does not appear to interfere with either activated peritoneal macrophage production of superoxide anion or H2O2-induced suppression of lymphocyte blastogenesis to elicit immune enhancement.

Animals↗

Evaluation of murine lymphocyte membrane potential, intracellular free calcium, and interleukin-2 receptor expression upon exposure to 1,1-dimethylhydrazine.

The effects of 1,1-dimethylhydrazine (UDMH) on several early events associated with lymphocyte activation were examined. The concentration of intracellular calcium ([Ca2+]i) and membrane potential of murine lymphocytes were found to be altered upon exposure to UDMH; [Ca2+]i was increased in murine thymocytes, while splenocytes exhibited membrane hyperpolarization. In addition, interleukin-2 receptor expression induced by in-vitro concanavalin A stimulation of murine splenocytes at 24 and 48 h in the presence of UDMH was not affected. UDMH may interfere with the ability of these two distinct lymphocyte populations to regulate normal ionic fluctuations, thus contributing to altered immune responsiveness.

Animals↗

Radiofrequency energy for rewarming of cold extremities.

Radiofrequency (RF) coils, developed to resonate at 27.12 MHz, were evaluated for effectiveness in rewarming thermally unprotected extremities of 5 male subjects. Bare hands or bare feet were exposed to 10.0 degrees C air during a total of four exposures for each subject. Deposition of RF energy for two of the exposures (one for the hands and one for the feet) began when a predetermined surface skin temperature was achieved. Rewarming continued for 10 min while fiber-optic sensors recorded surface skin temperatures at eight locations for each hand and four locations for each foot. Results were compared to data from identical exposures but without RF rewarming. Statistically significant (P less than 0.01) warming occurred at all of the monitored locations. Our results clearly demonstrate the ability of RF energy to warm hands and feet in cold environments.

Adult↗

The in vitro and in vivo effects of 1,1-dimethylhydrazine (UDMH) on murine lymphocyte subsets and Ia antigen expression.

1,1-Dimethylhydrazine or unsymmetrical dimethylhydrazine (UDMH) is a highly volatile and reactive compound used primarily as a liquid rocket propellant. Previous studies found UDMH to possess immunomodulatory activity similar to other hydrazine derivatives. Modulation of T lymphocyte subpopulations and Major Histocompatibility Complex Class II or Ia antigen were evaluated as possible mechanisms for this UDMH-induced immunomodulation. Murine lymphoid cell populations were examined by flow cytometry for changes in their cell surface marker percentages or relative number upon exposure to UDMH either in vitro or in vivo. The results show UDMH caused significant suppression of the T helper cell population derived from the thymus at the 75 mg/kg dose in vivo, but did not affect other lymphocyte subpopulations isolated from mesenteric lymph node, spleen or thymus at this or any other dose. In vivo exposure of mice at all doses of UDMH did not significantly alter expression of Ia antigens on adherent cell populations and expression of the Ia antigen following in vitro UDMH exposure was not affected as well. Results indicate that the immunomodulatory effects of UDMH are not mediated by phenotypic alteration of T lymphocyte subpopulations or Ia antigen.

Adjuvants, Immunologic↗

Lymphocyte and neutrophil dysfunction associated with hepatitis B virus and hepatitis non-A, non-B virus infection in the chimpanzee.

Chimpanzees were examined for the effect of viral hepatitis infections on specific and nonspecific immune response mechanisms. The data suggest that infection with either hepatitis B virus or hepatitis non-A, non-B virus may result in suppression of cellular immune response components. Mitogen-induced lymphocyte proliferation was lower in virus-infected chimpanzees than in naive animals. Neutrophils from virus infected animals exhibited decreased or altered chemiluminescence kinetics.

Animals↗

Subunit vaccine protects Macaca nemestrina (pig-tailed macaque) against simian T-cell lymphotropic virus type I challenge.

Five macaques received two vaccinations consisting of soluble human T-cell lymphotropic virus type I proteins from a cell/serum-free human T-cell lymphotropic virus type I-producing cell line. Five other macaques were vaccine controls. All were challenged with a simian T-cell lymphotropic virus type I-producing cell line. The vaccinated macaques generated a strong serological response to challenge as opposed to the control macaques. Western blot analysis of the sera showed that both groups recognized gag and env proteins, but the vaccinate's sera reacted better to the env proteins. Additionally, the antibody produced by both groups had antibody-dependent, complement-mediated cytotoxic activity toward both human and simian T-cell lymphotropic virus type I-infected target cells. The responses of lymphocytes and neutrophils, as measured by lymphocyte blast transformation and chemiluminescence response, respectively, showed no apparent difference between the vaccinates and controls. Testing for reverse transcriptase in lymphocyte supernatants revealed that the controls contained reverse transcriptase activity, while the vaccinates remained negative. The data presented here demonstrate that the vaccine was successful in protecting Macaca nemestrina from simian T-cell lymphotropic virus type I infection.

Animals↗

Prevalence of disease in nonviremic cats previously exposed to feline leukemia virus.

Feline leukemia virus status and antibody titer to feline oncornavirus-associated cell membrane antigen (FOCMA) were determined on plasma from 183 outpatient cats and 61 cats from 2 closed, FeLV-positive, multiple-cat households. Cats with FOCMA antibody titer had a significantly (P less than 0.02) higher prevalence of history of disease than did cats without FOCMA antibody. Diseases included upper respiratory tract infections, abscesses, ear infections, lower urinary tract infections, gastrointestinal disease, pneumonia, uterine infection, lymphadenopathy, fever of unknown origin, and bacterial infections. The FOCMA antibody titer was determined by use of an indirect fluorescent antibody test; titer greater than or equal to 1:16 was considered to be positive results. Lower mean FOCMA antibody titer was observed in young cats with history of disease (P less than 0.05) than in young cats without history of disease or in older cats with or without history of disease. Prevalence of FOCMA antibody titer was identical (38%) in young and adult cats, indicating cats likely were exposed to FeLV as kittens because a higher prevalence of FOCMA antibody titer in older cats would otherwise be expected.

Animals↗

Inhibition of phorbol ester-induced neutrophil chemiluminescence by FeLV.

Receptor-mediated activation is accompanied by phospholipid metabolism and by calcium fluctuation resulting in a chemiluminescence (CL) response in the neutrophil. This pathway involves activation of protein kinase C (PKC) and the NADPH oxidase. Artificial stimulants such as phorbol esters, specifically 12-O-tetradecanylphorbol-13-acetate (TPA), circumvent the receptor-mediated pathway and activate PKC resulting in a measurable CL response. Neutrophils from feline leukemia virus (FeLV) exposed cats were tested for their ability to generate a TPA-induced CL response. As compared to the non-FeLV-exposed specific-pathogen-free (SPF) control cat neutrophil CL responses, both viremic and nonviremic FeLV-exposed cats showed significant decreases in their CL responsiveness. Neither ultraviolet light-inactivated FeLV (UV-FeLV) nor protein components (FeLV-p15E and FeLV-p27) caused a significant decrease in the CL responses of the SPF cat neutrophils. The suppressed TPA-induced CL response from FeLV-infected cats may involve an intracellular mechanism not affected in vitro by exposure of the neutrophil to the virus or viral components.

Animals↗

In vitro replication and cytopathogenicity of the feline immunodeficiency virus for feline T4 thymic lymphoma 3201 cells.

Cytotoxic feline immunodeficiency virus (FIV) infection was established in feline T4 thymic lymphoma 3201 cells with the Petaluma isolate of the feline immunodeficiency virus (FIV-Petaluma). Mg2(+)-dependent, reverse transcriptase (Mg2+ RT) activity and FIV p24/28-positive cells were evident beginning at 18 days postinoculation (dpi). Cell death was observed beginning at 22 dpi, with a maximum of 40% dead (trypan blue dye exclusion at 26 dpi). This cytocidal change was not observed in cultured Crandell feline kidney fibroblasts similarly infected with FIV-Petaluma. The surviving cells grew out and a chronic FIV-producer cell line was established. The 3201 cell-derived FIV (FIV-3201) was far more virulent for FIV-naive feline 3201 cells, with FIV p24/28-positive cells and Mg2+ RT activity first detectable by 4-8 dpi and subsequent loss of cell viability detectable by 8-12 dpi. Maximum kill (40% dead) was observed at 16 dpi. Comparison between viral infectivity of FIV-Petaluma and FIV-3201 for FIV-naive 3201 cells showed an increase of 1 log10 tissue culture infectious doses (TCID50) by amplification/passage in 3201 cells. Cytologic and electron microscopic examination of 3201 cells in FIV-infected cultures showed frequent budding lentiviral particles. This lytic infection system opens the way to the routine detection, isolation, and quantitation of FIV from FIV-infected cats, to the large-scale propagation of the virus, and to a system for evaluation of the mechanisms of FIV lymphocytotoxicity and the development of therapies to counteract lentiviral cytopathicity.

Animals↗

Biological effects of staphylococcal protein A immunotherapy in cats with induced feline leukemia virus infection.

Biological effects of staphylococcal protein A (SPA) immunotherapy were studied in 5 viremic and 6 nonviremic cats with induced FeLV infection and in 6 control cats. The SPA therapy neither reversed FeLV viremia nor resulted in consistent improvement in humoral immune responses to FeLV antigens. However, SPA immunotherapy induced a proliferative response in bone marrow granulocytic lineage, possibly resulting in expression of FeLV-free mature neutrophils in the blood. Seemingly, viral burden and chemiluminescent responses were reversed in viremic cats during SPA immunotherapy.

Animals↗

Evaluation of a HTLV-1 subunit vaccine in prevention of experimental STLV-I infection in Macaca nemestrina.

Pig-tailed macaques were vaccinated with a human T-cell lymphotropic virus type I (HTLV-I) subunit vaccine. Vaccinates and controls were challenged with simian T-cell lymphotropic virus type I (STLV-I)-infected cells. Vaccination yielded antibody responses to HTLV-I and STLV-I gag and env precursors. Controls developed HTLV-I and STLV-I antibody to gag and tax protein. Immunization produced syncytium inhibiting antibody and cellular cytotoxicity to virus-infected cells. Reverse transcriptase activity was present in control macaques only, implying that the subunit vaccine was protective against STLV-I infection.

Animals↗

Efficacy of an HTLV-1 subunit vaccine in prevention of a STLV-1 infection in pig-tailed macaques.

Three pig-tailed macaques were vaccinated twice, four weeks apart, with a human T-cell lymphotropic virus type 1 (HTLV-1) subunit vaccine. Four weeks post-vaccination, the vaccinated macaques and two control monkeys were challenged with a simian T-cell lymphotropic virus type 1 (STLV-1)-infected cell line. Following the first vaccination, an antibody response developed to HTLV-1 and STLV-1 viral proteins as visualized by Western blot. The antibody recognized both gag and env protein precursors and the titer remained elevated after the second vaccination. After challenge, the antibody titers of the vaccinates increased. The controls also developed HTLV-1 and STLV-1 specific antibody which recognized the gag precursor and to a lesser extent the putative tax protein. Immunized monkeys also produced syncytium inhibiting antibody primarily toward HTLV-1-infected cells and to a lesser extent toward STLV-1-infected cells. Control monkeys produced negligible amounts of syncytium inhibiting antibody. Additionally, both polymorphonuclear (PMN) and mononuclear (MNC) cells were examined. The PMN population was tested for its ability to generate an oxidative burst. Neither vaccination nor challenge had any significant effect on the PMN CL response. The MNCs were tested for their capability to proliferate after stimulation. Again, no significant change occurred. However, when examined for cell-mediated cytotoxicity, the MNCs from immunized monkeys produced greater cytotoxic activity against the HTLV-1-infected cell line than the MNCs from control monkeys. In order to determine if the immunized monkeys were protected by the subunit vaccine against the STLV-1 challenge, reverse transcriptase (RT) activity was measured in the five monkey's MNCs. RT activity was exclusively present in the non-immunized, control monkeys implying that the HTLV-1 subunit vaccine was successful in protecting the pig-tailed macaques from the STLV-1 infection.

Animals↗