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Biomedical subjects

M Løvik

Publications and source records attributed to M Løvik.

At least 55 records · Page 3Linked to original sources

PCDDs, PCDFs, and PCBs in human blood in relation to consumption of crabs from a contaminated Fjord area in Norway.

Consumption of fish and shellfish from contaminated areas may be an important source of human exposure to persistent organohalogen compounds such as polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs). We determined concentrations of 2,3,7,8-substituted PCDDs and PCDFs and 19 PCB congeners in whole blood samples from three groups of men, 40-54 years of age, with different consumption levels of crabs from a fjord area in southern Norway polluted with organochlorine compounds from a magnesium production plant. A significant increase of many PCDD/PCDF congeners was found in the blood when comparing the referents, moderate-, and high-intake groups. The greatest difference was observed for several of the PCDFs that are characteristic for the contamination of the marine biota of the fjord. PCBs, in general, play a minor role in the contamination of the fjord by the magnesium production process, except for the highly chlorinated congeners such as PCB-209. Nevertheless, almost all PCBs increased from the referents to the high-intake group. However, the relative concentrations of several highly chlorinated PCBs (particularly PCB-209) in blood are unexpectedly low compared to their abundance in crabs, indicating low uptake of these congeners. The exposure to PCDDs/PCDFs from crab consumption calculated from individual body burdens of these compounds were in good agreement with the intake estimated from previously measured concentrations in crabs, reported fishing sites, and consumption. Almost all subjects in the high-intake group exceeded the tolerable weekly intake of 35 pg TEQ/kg body weight/week proposed by a Nordic Expert Group.

Adult↗

Virulence of Streptococcus pneumoniae in mice: a standardized method for preparation and frozen storage of the experimental bacterial inoculum.

Animal models of pneumococcal infection are important to evaluate the protective capacity of new vaccine candidates. We have established a method to prepare and store the experimental inoculum without loss of virulence or number of bacteria. This allows a standardized inoculum from the same culture batch to be used in several experiments. Pneumococci were cultured to mid-logarithmic growth phase in Todd-Hewitt broth with 17% fetal calf serum. The bacterial broth was distributed into smaller volumes and immediately frozen on liquid nitrogen and stored at -70 degrees C. We have tested the virulence of five different pneumococcal serotypes in BALB/c, C57BL/6, and NIHS mice using inocula prepared by this method and stored without loss of virulence for up to 4 years. Serotypes 1, 4, 5 and 8 were highly virulent for the strains of mice tested whereas type 6B showed lower virulence and a peculiar, protracted course of infection. There were no clear differences in virulence between the different strains of mice with the exception of serotype 6B, which showed higher virulence in BALB/c and NIHS mice than in C57BL/6 mice.

Animals↗

The antibody response to secondary immunization with pneumococcal polysaccharides in mice.

The benefit of re-immunization with pneumococcal polysaccharide vaccine is an important question in clinical practice. In an experimental model, BALB/c and CBA/J mice were re-immunized s.c. with a 23-valent pneumococcal polysaccharide vaccine at various time intervals after a first immunization with the same vaccine. The antibody response after the secondary immunization showed similar kinetics as after primary immunization, and was mainly an IgM antibody response. Re-immunization at 28 days or earlier induced a decrease in the serum antibody levels to the vaccine. Reimmunization at 120 days or later induced higher antibody levels than after the first immunization. Significant increases in antibody levels to serotypes 1, 4, 7F and 19F out of six serotypes tested were observed. In CBA/J mice, but not in BALB/c mice, the dose used for primary immunization appeared to influence the magnitude of the antibody response to secondary immunization. Our results indicate that the time interval between primary and secondary immunization is an important determinant with regard to the magnitude of the antibody response to re-immunization with pneumococcal polysaccharide vaccine.

Animals↗

[Risk of AIDS in the Oslo HIV-cohort study. A comparison between homosexual men, intravenous addicts and heterosexual persons].

In order to study differences in risk of the development of AIDS in different groups of HIV infected subjects, 151 homosexual men, 110 intravenous drug users (IVDUs) and 36 heterosexually infected persons without major signs of HIV infection at entry to the study were enrolled in a cohort study. The mean follow-up time was 35 months. At the end of follow-up 40 subjects (13%) were diagnosed as having AIDS. This represented 20% (31/151) of the homosexual men, 7% (8/110) of the IVDUs and 3% (1/36) of the heterosexual subjects. The probability of being AIDS-free 36 months after entering the study was 0.88 (0.84-0.92, 95% CI) for the total study population, 0.83 (0.77-0.90) for the homosexual men, 0.92 (0.86-0.99) for IVDUs and 0.93 (0.91-1.0) for heterosexual subjects (p < 0.05, log rank test). In a Cox regression analysis, adjusting for CD4+ cell count at study entry, the relative risk of AIDS progression was 2.4 (1.1-5.2) for homosexual men and 0.3 (0.04-2.4) for heterosexual subjects, compared with IVDUs. The results demonstrate a higher risk of AIDS for homosexual men during the follow-up period.

Acquired Immunodeficiency Syndrome↗

Antibody response to pneumococcal polysaccharide vaccine in young, adult and old mice.

The anti-pneumococcal antibody response was studied in young (5-week-old) and adult (10-week-old) BALB/c and CBA/J mice and in adult (9-10-week-old) and old (12-, 18- and 24-month-old) AB6F1 and B6D2F1 mice after s.c. immunization with a 23-valent pneumococcal polysaccharide vaccine. Both young and adult mice showed a significant IgM antibody response to the vaccine 6 days after immunization with 1-11 micrograms antigen. There were significant immune responses to serotypes 1, 2, 4 and 7F in contrast to small responses to serotypes 14, 19F and 23F after immunization with the vaccine. One month after immunization, there were only marginal differences in IgM anti-pneumococcal antibody levels to the vaccine (anti-PPS) between immunized and unimmunized BALB/c mice, whereas in CBA/J mice the anti-PPS remained higher in immunized than in unimmunized mice. Immunization of old mice induced a significant IgM antibody response 6 days after immunization, but the anti-PPS thereafter decreased rapidly towards preimmunization values in AB6F1 mice. A significant IgG anti-PPS was not detected in any of the mice studied. The IgA anti-PPS tended to vary over time with no consistent pattern. It is important to carefully consider age and strain of the mice used when studying the immune response to pneumococcal polysaccharide antigens.

Aging↗

Murine monoclonal antibodies against pneumococcal capsular polysaccharide types 4, 8, 22F and 19A/19F.

Monoclonal antibodies (MAbs) were produced against pneumococcal capsular polysaccharides after subcutaneous immunization of BALB/c mice with a 23-valent vaccine (Pneumovax N, Merck, Sharp & Dohme). Selected antibodies were tested in ELISA against individual polysaccharides from 23 different pneumococcal types and in a dot blot assay with heat-killed whole bacteria adhered to nitrocellulose paper. Three MAbs (isotype IgM) were found to be specific for types 4, 8 and 22F, respectively, whereas one (isotype IgA) reacted both with 19A and 19F. Very mild acid hydrolysis of the capsular polysaccharides resulted in loss of reaction with the antibodies.

Animals↗

SCID-Hu mice immunized with a pneumococcal vaccine produce specific human antibodies and show increased resistance to infection.

Seventy-eight severe combined immunodeficiency (SCID) mice were administered intraperitoneally 1 x 10(7) to 9 x 10(7) human peripheral blood mononuclear cells (PBL) in five experiments. Human immunoglobulin G (IgG) was detected in 70 to 88% of these SCID-PBL-Hu mice after cell transplantation, and all four subclasses were present. The total concentration of human IgG varied from less than 1 to 10.2 g/liter. The SCID-PBL-Hu mice with high concentrations of human IgG regularly had mono- or oligoclonal human IgG bands in serum, as demonstrated by agarose gel electrophoresis. Of the SCID-PBL-Hu mice that were immunized with a 23-valent pneumococcal polysaccharide vaccine, 63 to 78% developed a significant human IgG antipneumococcal antibody response, whereas only very low levels of human IgM and no human IgA antipneumococcal antibodies could be detected. Twelve to twenty-two percent of the SCID-PBL-Hu mice showed signs of leakiness; these mice developed a significant mouse IgM antipneumococcal antibody response and no human antibodies. SCID-PBL-Hu mice were challenged intraperitoneally with 10 50% lethal doses of Streptococcus pneumoniae serotype 4 to study the protective effect of immunization with pneumococcal vaccine. The immunized SCID-PBL-Hu mice showed less bacteremia than did all control groups, and survival was 45 to 60%. None of the unimmunized SCID-PBL-Hu mice survived.

Adult↗

Local reactivity, local resistance and systemic dissemination in Mycobacterium lepraemurium (MLM) infection.

Local reactivity measured as swelling of the infected footpad, local resistance to bacterial multiplication, and capacity to limit systemic dissemination were studied in C57BL, C3H/Bom, C3H/HeJ, and A/Sn mice inoculated with Mycobacterium lepraemurium. C57BL mice developed a strong local reaction with a sudden onset, and effectively limited local multiplication as well as systemic dissemination of bacteria to the liver and spleen as determined 19 weeks after the inoculation. C3H/Bom mice showed no local reaction, had high numbers of bacteria locally, and had extensive systemic dissemination of the infection. C3H/HeJ mice, on the other hand, developed a small local reaction and had less systemic dissemination of bacteria than C3H/Bom mice. In C57BL mice and in the two C3H substrains local reactivity, local resistance to infection, and resistance to systemic spread of the infection paralleled each other. In contrast, A/Sn mice showed a small local reaction, had the most extensive bacterial multiplication at the site of inoculation of the four mouse strains tested, and at the same time were the mice that most effectively restricted systemic dissemination of the infection. Thus, the mechanisms restricting local bacterial multiplication may be different from the mechanisms limiting bacterial dissemination. Neither bacterial growth locally at the site of subcutaneous inoculation in the footpad, nor systemic dissemination of the infection, followed a mouse strain pattern consistent with the Ity/Lsh/Bcg gene model. In experimental mycobacterial infection both local bacterial growth at the site of inoculation and systemic dissemination should be determined.

Animals↗

Effect of aging on antimicrobial immunity: old mice display a normal capacity for generating protective T cells and immunologic memory in response to infection with Listeria monocytogenes.

Old (19 to 30 mo) and young adult (11 to 16 wk) AB6F1 mice of both sexes were compared in terms of their capacity to resist infection with Listeria monocytogenes. The LD50 was found to be two to four times higher for old than for young mice, and the time to death was longer for old mice. Enumeration of bacteria in the livers and spleens showed that old mice restricted growth of Listeria more effectively than young mice during the preimmune phase of infection, the difference being detectable as early as 12 to 24 hr after bacterial inoculation. Therefore, to ensure a similar level of infection in old and young mice, old mice had to be given a larger inoculum. Indeed, it was found that, provided the size of the bacterial inoculum was adjusted to make the level of immunizing infection the same, old mice generated similar levels of anti-Listeria immunity as young mice, as measured by their ability to generate splenic T cells capable of adoptively immunizing young recipients against lethal challenge infection. Furthermore, the level of memory immunity to reinfection 28 to 117 days after immunizing infection was similar in old and young mice. The results indicate, therefore, that old mice have no defect in their capacity to generate T cell-mediated anti-Listeria immunity.

Aging↗

Delayed-type hypersensitivity after immunization with ultrasonicated Mycobacterium lepraemurium in C3H and C57BL mice.

Subcutaneous immunization with ultrasonicated Mycobacterium lepraemurium (MLMSon) in incomplete Freund's adjuvant (IFA) induced long-lasting skin reactivity with the kinetics of a tuberculin-type delayed hypersensitivity (DTH) reaction in both C3H and C57BL mice. The reactivity generally was stronger in C57BL than in C3H mice, and with increasing doses of MLMSon test antigen the local reaction increased more in C57BL than in C3H mice. Pretreatment of C3H mice with cyclophosphamide before immunization caused a shift in the dose-response curve so that the local reaction increased more with increasing doses of test antigen. Histological examination of the reaction elicited by MLMSon in immunized mice revealed a predominantly mononuclear cell infiltrate, and local reactivity could be transferred by immune cells but not by immune serum. The local reaction elicited by MLMSon exerted an adjuvant effect on the induction of DTH to sheep erythrocytes. Thus, MLMSon in IFA given subcutaneously induced stable DTH that conformed to the criteria for tuberculin-type DTH.

Adjuvants, Immunologic↗

Survival of Mycobacterium lepraemurium in C57BL mice after acquired protective immunity.

The protective immune response against Mycobacterium lepraemurium (MLM) in C57BL mice has been shown to stop the increase in bacillary numbers and the dissemination of bacilli, but the acid fast bacilli are not cleared from the tissues. Persistence of viable bacilli was indicated by a significant increase in the number of acid fast bacilli in the footpad of C57BL mice that were treated with cortisone acetate several weeks after the onset of the immune response. Bacilli harvested 9 and 16 days after inoculation into immune C57BL mice showed only a marginally detectable loss of viability as determined by bacillary multiplication after transfer into susceptible C3H mice. Twenty-six weeks after being inoculated into immune C57BL mice a small proportion of the bacilli was found still to be alive. A similar finding was done 15 weeks after primary inoculation of MLM into mice that developed an apparently effective protective immune response 4 weeks after being inoculated. Sixty-seven weeks after inoculation of immunized C57BL mice with MLM, bacillary numbers in the footpad were as with patent immunity, but the bacilli were found to be fully viable, suggesting incipient reactivation of the infection. When bacillary numbers were followed over a period of 52 weeks in the organs of normal C57BL mice inoculated with a low dose of bacilli it was found that after a plateau phase bacillary numbers started to increase again. Thus, in all experiments part of the bacillary population had survived the protective immune response against MLM in C57BL mice.

Animals↗

Induction of immunity against live Mycobacterium lepraemurium: a requirement for viable bacilli?

Live Mycobacterium lepraemurium (MLM) bacilli, bacilli killed by irradiation or heat, and the water-soluble components of ultrasonicated bacilli (MLMSon) were compared as immunizing and eliciting antigens in C57BL mice which are high-responders to live MLM. The latency period preceding the development of a local granulomatous reaction in normal mice inoculated subcutaneously in the footpad with live MLM was reduced, and the reaction became larger when the dose of bacilli was increased. Immunization with MLMSon induced only weak initial reactivity against an inoculum with live bacilli, but the development of stronger reactivity was accelerated and the magnitude of the local reaction that then developed was increased. MLMSon-immunized mice showed some reactivity also against heat-killed bacilli. Killed bacilli caused the development of a small, late local reaction in normal mice, but no local reactivity was detected upon challenge with live and killed MLM in mice immunized with killed bacilli. However, a local reaction was elicited by MLMSon, which was thus a more potent eliciting antigen than intact bacilli, and MLMSon and whole killed bacilli appeared to induce immune reactivity with overlapping antigen specificities. Subcutaneous inoculation with live bacilli induced reactivity against live MLM but not against MLMSon and not against whole killed MLM, except for a transient early (24 hr) reaction elicited only with a large dose of killed bacilli. The development of a lasting local reaction against killed bacilli was found to be suppressed in mice immunized with live bacilli. Live bacilli and dead MLM antigen appeared to have largely different specificities as inducing as well as eliciting antigens.

Animals↗

Immunization of highly susceptible C3H mice with ultrasonicated Mycobacterium lepraemurium (MLM) bacilli facilitates the development of increased resistance during MLM infection.

C3H mice were immunized subcutaneously with water soluble antigens of ultrasonicated Mycobacterium lepraemurium bacilli (MLMSon-S) in Freund's incomplete adjuvant (FIA) and challenged with 1 X 10(6)-1.25 X 10(8) live MLM bacilli inoculated into the foot pad. No swelling of the infected foot pad and no differences in bacillary multiplication and dissemination between the immunized mice and the control animals were observed in the first nine weeks. From nine weeks on, a small foot pad swelling developed in the immunized mice. Twenty weeks after inoculation, the number of bacilli in the foot pad, the popliteal lymph node, and the spleen was significantly lower in the immunized mice than in the normal controls after challenge with the lowest bacillary doses. Cyclophosphamide (CY) pretreatment did not increase the effect of immunization. The addition of MLM cell wall fragments to the emulsion used for immunization tended to increase the difference between immunized and normal animals, while no further increase of the immunization effect was obtained by the use of Freund's complete adjuvant (FCA). A tendency toward a plateau phenomenon for the multiplication of MLM bacilli was observed in the normal mice. In nonimmunized mice, CY treatment caused some reduction in bacillary numbers in the foot pads, and reinfection experiments suggested that a small reduction in susceptibility had been induced by the priming infection. Although unable to prevent a progressive course of the infection, genetically low-resistant C3H mice were able to modify the development of the infection by mechanisms that were activated by the infection itself. Similar mechanisms were facilitated by immunization with MLMSon-S.

Animals↗

H-2-linked gene(s) influence the granulomatous reaction to viable Mycobacterium lepraemurium in the mouse.

The genetic control of the granulomatous response to viable Mycobacterium lepraemurium (MLM) was studied in C3H and C57BL/6 inbred strains, BXH recombinant inbred strains, (C3H X C57BL) F1 hybrids, and backcross mice. The results indicate that an autosomal dominant gene, or linked complex of genes, has a marked influence on the footpad reaction to viable MLM. The distribution of responders and non-responders among 12 BXH recombinant inbred strains and linkage analysis in C3H X (C3H X C57BL)F1 backcross mice indicated that the response gene(s) are linked to the H-2 complex on chromosome 17. The same gene(s) also influence host restriction of MLM multiplication and thus appear to be the first H-2-linked gene(s) influencing resistance to a bacterial infection.

Animals↗

Induction of delayed type hypersensitivity against ultrasonicated Mycobacterium lepraemurium bacilli without simultaneous local reactivity against live bacilli or protective immunity.

Delayed type hypersensitivity (DTH) was induced in C3H mice by subcutaneous immunization with Mycobacterium lepraemurium (MLM) antigens in Freund's complete (FCA) or Freund's incomplete (FIA) adjuvant. The total ultrasonicate (MLMSon-P) of MLM bacilli as well as the water soluble fraction (MLMSon-S) of this ultrasonicate was found effective. MLMSon-S was used as the test antigen. Specific DTH also developed after immunization with heat-killed MLM bacilli in FIA, but not with heat-killed bacilli in saline. Some mice were pre-treated with cyclophosphamide (CY) or splenectomized to augment the effect of immunization. In no instance was DTH to MLMSon-S accompanied by detectable local reactivity to live MLM bacilli measured as swelling of the infected footpad or by reduced multiplication or dissemination of the bacilli during the first 11 weeks after inoculation. As determined by testing in the infected footpad 8 weeks after inoculation, MLM infection did not induce DTH to MLMSon-S in non-immunized mice, and MLM infection was found to neither augment nor suppress established DTH to MLMSon-S. The experiments thus demonstrated a clear dissociation between DTH to MLMSon-S and local reactivity to live MLM bacilli, as well as between DTH to MLMSon-S and protective immunity to MLM infection.

Animals↗