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Biomedical subjects

O Strannegård

Publications and source records attributed to O Strannegård.

At least 19 recordsLinked to original sources

Discrepant effects of interferon murine syngeneic ascites tumors and their solid metastasizing counterparts.

The effects of interferon on mice with syngeneic tumors growing either intraperitoneally or as solid tumors were analyzed. The same dose that depressed the growth of ascites tumors, enhanced growth and in one case metastasizability of the corresponding solid tumors. The possibility that this was due to some host reaction is discussed. It seems important to develop animal models for analyzing interferon effects before treatment is initiated in human tumor disease.

Animals

T lymphocytes and blood eosinophils in early infancy in relation to heredity for allergy and type of feeding.

T lymphocytes in 50 one-month-old infants were determined and correlated to heredity for allergy, blood eosinophil counts, and type of feeding. It was found that infants with heredity for atopy had significantly lower relative numbers of T lymphocytes than infants without heredity (p less than 0.05). This difference was particularly obvious in heredity for asthma on the paternal side (p equals 0.001). There was an inverse correlation between T lymphocyte counts and blood eosinophil counts in infants who were cow's milk-fed; i.e., low T lymphocyte counts were associated with high blood eosinophil counts (r = -0.59, p less than 0.01). T lymphocyte counts were not correlated to the type of feeding, whereas blood eosinophils were significantly higher in the cow's milk-fed than in the breast-fed group (p less than 0.01). The results suggest that atopic allergy may be associated with a genetically determined lymphocyte defect.

Asthma

Effects of leukocyte and fibroblast interferon on events in the fibroblast cell cycle.

Serum-depleted human foetal skin fibroblasts were stimulated by addition of 10% foetal calf serum to proliferate synchronously for at least one cell cycle. This proliferation was suppressed by leukocyte or fibroblast interferon (IF), which prolonged the G1 phase and diminished the rate of DNA synthesis during the S phase in a dose-dependent manner. When used in identical concentration, as judged in terms of units of antiviral activity, fibroblast IF had more pronounced effects on cell cycle events than leukocyte IF. Interferon exerted its effect in early G1, before the cells were irreversibly committed to DNA synthesis.

Cell Cycle

Stimulatory and inhibitory effects of cyclic AMP on lymphocytes from atopic children.

The effect of cholera toxin and dibutyryl cAMP on mitogen-activated lymphocytes from atopic and non-atopic individuals was studied. Cholera toxin enhanced stimulation by phytohemagglutinin of cells from small children but not from adults. Dibutyryl cAMP at low concentration (less than 10(-5) M) significantly enhanced the lymphocyte response to mitogens in some, but not all individuals. High concentrations, on the other hand, were consistently inhibitory. In atopic children, the lymphocyte response to T cell mitogen was significantly less stimulated by cholera toxin, and more inhibited by dibutyryl cAMP than the response of cells from non-atopic matched controls. Thus, T cells from atopic individuals appear to have an altered sensitivity to the action of cAMP, possibly resulting in an impaired balance between helper and suppressor T cells. The hypothesis is advanced, that such an altered balance is causally related to hyperproduction of IgE resulting in atopic disease.

Adolescent

In vitro differences between the lymphocytes of normal subjects and atopics.

Recently evidence has accumulated that atopic disease is associated with a deficiency of thymus-derived (T) cells. This deficiency appears to be primary, rather than secondary to treatment or manifestations of the disease. Results of in vitro studies indicate that the deficiency is most pronounced in certain subpopulations of T cells, and therefore a disturbance of the balance between subsets of T cells, notably suppressor and helper T cells, may develop in vivo in atopics. Some results suggest that there is indeed a relative deficiency of suppressor T cells in atopic diseases, and thus the hyperproduction of IgE which is associated with these diseases may be explained. The cause of the T cell deficiency in atopy may be a basal cellular abnormality, manifested e.g. as increased sensitivity to inactivation by physiological substances, notably to agents which increase intracellular levels of cyclic AMP. It is equally possible that the T cell deficiency is a direct consequence of subnormal production of certain thymic hormones.

Animals

Modulation of immune responses in newborn and adult mice by interferon.

Interferon was found to have both suppressive and enhancing effects on the antibody response in newborn and adult mice. Evidence was obtained that these effects are primarily evoked during the initial steps controlling cell proliferation. Stimulation of thymus and spleen cells with a T-cell mitogen was enhanced by low doses and suppressed by high doses of interferon. Treatment of parental spleen cells with interferon before injecting them into immunized F1 hybrid mice resulted in an enhanced allogeneic effect. These results are compatible with the hypothesis that interferon affects T cells and has an immunoregulatory role, either by inhibiting the action of suppressor cells or by promoting immunological maturation.

Animals

Immune reactivity of Visna virus-inoculated mice.

Visna virus inoculation of mice before immunization with unrelated antigens caused suppression of humoral and cell-mediated immune responses. The immunosuppressive effect was dependent on the virus dose and time of administration. The number of "background" antibody-producing spleen cells increased slightly after inoculation of Visna virus. Heat treatment of Visna virus abolished its immunosuppressive effect. Replication of Visna virus in mice seemed to be a prerequisite for its immunomodulating effect.

Animals

Increased sensitivity of lymphocytes from atopic individuals to histamine-induced suppression.

Histamine depressed lymphocyte reactivity to phytohemagglutinin and, to a lesser degree, concanavalin A, when administered simultaneously with mitogen to lymphocyte cultures. Addition of histamine at later times to the cultures appeared to have a slightly enhancing effect on the lymphocyte response. Stimulation of lymphocytes with pokeweed mitogen was in some cases enhanced, even by high concentrations of histamine. Lymphocytes from atopic individuals were more sensitive to the inhibitory effect of histamine than lymphocytes from nonatopic individuals. The sensitivity appeared age-dependent, but within each age group histamine evoked significantly more suppression on lymphocytes from atopic than from nonatopic individuals. The possibility that the altered reactivity of lymphocytes to histamine, which appears to be associated with atopic allergy, is of pathogenic importance, is discussed, and a hypothesis for the development of atopic disease is proposed.

Concanavalin A

Enhancement of the allogeneic effect by irradiation of transferred cells.

Hot-pulse treatment of parental thymus or spleen cells increased their ability to simulate antibody synthesis in F1 hybrid recipient mice. A similar effect was obtained after treatment of the cells with low doses of X-irradiation. Likewise, irradiation of syngeneic unprimed cells made them stimulatory on antibody production. The production of IgG, IgM as well as IgE antibodies was enhanced after transfer of irradiated cells. The results suggest that irradiation preferentially inactivates suppressor cells, that are present in the thymus and the spleen.

Animals

Immune suppression induced by acetoacetylated antigen.

Injection of acetoacetylated antigen into rabbits with an ongoing reagin response abrogated this response. The possibility that this phenomenon might be due to activation of suppressor cells was studied in mice. Thymus or spleen cells from animals which had been primed with acetoacetylated antigen were able to suppress the IgG and IgM antibody response upon transfer to syngeneic mice. Maximal suppressive effect was observed 12-14 days after priming with native as well as acetoacetylated antigen. The IgG and IgM responses were equally affected by the transferred suppressor cells.

Acetoacetates

Immunological properties of ampicillin polymers.

The immunologic effects of ampicillin polymers were studied in mice and rabbits. Polymerized ampicillin--in contrast to monomers--had a suppressive effect on the antibody response to penicilloylated proteins. Unfractionated ampicillin polymer, and high molecular weight fractions were found to have an immunogenic effect in mice, when tested by a haemolytic plaque assay. The immunogenic effect of variously sized polymers did not correspond to their antigenic activity as reflected by passive cutaneous anaphylaxis experiments.

Ampicillin

Influence of serum from atopic children on T lymphocytes.

The relative and absolute number of peripheral T cells was found to be depressed in atopic children. Sera from atopic children had slightly less stimulatory effects on lymphocyte DNA synthesis induced by PHA, Con A and PPD, than sera from nonatopic children. This finding indicates an occurrence of inhibitory factor(s) in atopic serum. Sera from some severely ill atopic patients almost completely abolished mitogen-induced lymphocyte DNA synthesis. Inhibition by atopic serum appeared to be an early event in lymphocyte mitogenesis and not due to CRP, IgE or factors binding to mitogens. Lymphocytes from atopic children were no more sensitive to suppressive influences of atopic serum factors than were lymphocytes from adult blood donors. Normal serum enhanced mitogen-induced DNA synthesis more in lymphocytes from adult blood donors than in those from atopic children. The results indicate that, although the T cell defect in atopy may be partly caused by serum factors, occurring during clinical allergic disease, the main reason for the defect is probably an altered reactivity of the T lymphocytes in atopic individuals.

Adolescent

Evaluation of the hemolysis-in-gel test for the screening of rubella immunity and the demonstration of recent infection.

The hemolysis-in-gel method for detection of antibodies to rubella virus gave results which correlated well with results of hemagglutination inhibition and neutralization tests. With a diffusion time of 24 or 48 h, a linear correlation was obtained between the logarithm of antibody concentration and the diameter of the hemolytic zone. Fourfold, and even twofold, differences in serum antibody concentrations were shown to give statistically significant differences in hemolytic zone diameters. It could therefore be concluded that the hemolysis-in-gel test is well suited for the serological diagnosis of primary rubella infection, as well as of reinfection. The sensitivity of the hemolysis-in-gel test was comparable to that of the hemagglutination inhibition test. Pigeon erythrocytes were superior to sheep erythrocytes for use in the test. Studies of the antibody response after natural rubella infection or vaccination showed that the appearance and persistence of antibodies measured by hemolysis in gel is similar to that of hemagglutination inhibition antibodies.

Animals