The genetic basis for susceptibility to Rift Valley fever disease in MBT/Pas mice.

The large variation in individual response to infection with Rift Valley fever virus (RVFV) suggests that host genetic determinants play a role in determining virus-induced disease outcomes. These genetic factors are still unknown. The systemic inoculation of mice with RVFV reproduces major pathological features of severe human disease, notably the hepatitis and encephalitis. A genome scan performed on 546 (BALB/c × MBT) F2 progeny identified three quantitative trait loci (QTLs), denoted Rvfs-1 to Rvfs-3, that were associated with disease susceptibility in MBT/Pas mice. Non-parametric interval-mapping revealed one significant and two suggestive linkages with survival time on chromosomes 2 (Rvfs-1), 5 (Rvfs-3) and 11 (Rvfs-2) with respective logarithm of odds (LOD) scores of 4.58, 2.95 and 2.99. The two-part model, combining survival time and survival/death, identified one significant linkage to Rvfs-2 and one suggestive linkage to Rvfs-1 with respective LOD scores of 5.12 and 4.55. Under a multiple model, with additive effects and sex as a covariate, the three QTLs explained 8.3% of the phenotypic variance. Sex had the strongest influence on susceptibility. The contribution of Rvfs-1, Rvfs-2 and Rvfs-3 to survival time of RVFV-infected mice was further confirmed in congenic mice.

Bayesian inference of ion velocity distribution function from laser-induced fluorescence spectra.

The velocity distribution function is a statistical description that connects particle kinetics and macroscopic parameters in many-body systems. Laser-induced fluorescence (LIF) spectroscopy is utilized to measure the local velocity distribution function in spatially inhomogeneous plasmas. However, the analytic form of such a function for the system of interest is not always clear under the intricate factors in non-equilibrium states. Here, we propose a novel approach to select the valid form of the velocity distribution function based on Bayesian statistics. We formulate the Bayesian inference of ion velocity distribution function and apply it to LIF spectra locally observed at several positions in a linear magnetized plasma. We demonstrate evaluating the spatial inhomogeneity by verifying each analytic form of the local velocity distribution function. Our approach is widely applicable to experimentally establish the velocity distribution function in plasmas and fluids, including gases and liquids.

Tumor immunity induced by preimmunization with BALB/c mouse myeloma protein.

Prior sc immunization of BALB/c mice with 1 mg isolated M component of MOPC-11 mouse myeloma resulted in significant relative immunity to subsequent sc or ip challenge with 10(4) living cells from the same plasmacytoma. However, challenges of 10(5) and 10(6) tumor cells overcame immune status engendered by preimmunization with M component. Despite evidence for the specificity of the immunity induced by one isolated M component as opposed to another, no clear cytotoxic antibody, cell-mediated tumor-cell lysis, or predominance of either humoral or cell-mediated immune mechanisms were demonstrated. These findings were compatible with a relatively slight tumor-specific antigenicity of M components expressed on tumor surfaces, compared with the tumor specificity of other tumor-related, cell-surface antigens.

Cellular and humoral immune responses of mice during immunological enhancement of an allogeneic tumor.

Spleen cells obtained from C57BL/Ks (Ks, H-2d) mice carrying passively enhanced Sarcoma I (Sa I, H-2a) tumors were tested for alloantibody formation, lymphocyte blastogenesis, antibody-dependent cellular cytotoxicity, and cell to cell cytotoxicity. Assays were usually performed approximately 6 weeks after tumor inoculation. The results of these assays indicate that spleen cells from tumor-bearing mice are actively synthesizing alloantibody, but have a depressed blastogenic response to phytohemagglutinin and allogeneneic cells, and manifest no detectable cytotoxic activity in 51Cr release assays for antibody-dependent or cell to cell cytotoxicity. The absence of cell to cell cytotoxicity was specific and could not be attributed to the activity of suppressor cells acting in vitro, or to immunoglobulin secreted during the in vitro assay. These results indicate that Ks mice carrying immunologically enhanced Sa I tumors have a strong humoral response but a defective cellular response to the alloantigens of their tumors. These results are compatible with a mechanism of immunological enhancement which involves suppression of the development of the cellular immune response throughout the course of tumor growth.

Evidence of altered T-lymphocyte number and proliferative responses in genetically epilepsy-prone rats.

Genetically epilepsy-prone (GEPR-9) rats exhibit decreased antibody plaque-forming cell responses following immunization. We examined the hypothesis that this immunosuppression was due to deficits in the number or proliferative responses of T-lymphocytes. Splenocyte responses to concanavalin A and pokeweed mitogen were significantly greater in GEPR-9 rats than controls. Flow cytometric analysis indicated that GEPR-9 rats possess an increase in T-cells associated with the T-helper phenotype. The increased proportion of T-helper cells in GEPR-9 rats may underlie their enhanced proliferative responses to T-cell mitogens. These results clearly indicate that the failure of the GEPR-9 rat to respond to a T-dependent antigen in vivo is not due to a lack of T-helper activity.

Higher levels of erythrocyte membrane fluidity in sprinters and long-distance runners.

Erythrocyte membrane fluidity was measured in male sprinters and long-distance runners by a spin-label method. The membrane fluidity was higher in long-distance runners than in sedentary subjects for both measurements by use of two stearic acid spin labels (SAL), 12- and 16-SAL, which represent the fluidity at two different depths of lipid bilayer. In the 12-SAL measurement, higher levels were also evident in sprinters than in sedentary subjects. Increases in the C20:5, C22:5, and total polyunsaturated acyl chains were evident in membrane phospholipids, whereas the C18 and total saturated acyl chains were decreased in long-distance runners compared with sedentary subjects. Only levels of C22:5 were higher in the sprinters than the sedentary subjects. Membrane cholesterol and phospholipid classes did not differ among the three groups. A higher level of erythrocyte membrane fluidity was observed in the athletes, more obviously in the long-distance runners, which was related to the altered phospholipid acyl chain composition. The change may contribute to the beneficial effects on erythrocyte functions related to microcirculation in athletes.

Evidence of immunosuppression in the genetically epilepsy-prone rat.

Immune system function was examined in the genetically epilepsy prone (GEPR-9) rat and non-epileptic Sprague-Dawley control rats. Significant decreases in direct and indirect plaque-forming cell responses were observed in GEPR-9 rats immunized with sheep erythrocytes. Serum levels of IgM were also decreased in non-immunized GEPR-9 rats, providing additional evidence of immunosuppression. However, total serum levels of IgG were three-fold greater in GEPR-9 rats compared to control. These results suggest that the nature of the immune system deficit in the GEPR-9 is complex and may involve an active T-cell population stimulating an overproduction of IgG leading to a diminished capacity to respond to new antigen challenges. This immunological defect may underlie the enhanced susceptibility of GEPR-9 rats to infectious agents. The specific cause of this immune dysfunction is not known. Possible etiological factors include a breakdown in the communication between cells within the immune system or an alteration of neuroendocrine modulation of immune responses.

Differential immune response in two handled inbred strains of mice.

C57BL/10J and BALB/cJ mice, outfostered at birth to C3H/2Ibg dams were subjected to handling on days 1 through 20 of life. Their plaque forming cell (PFC) response to sheep red blood cells as adults on day 5 post-immunization was compared to the PFC response in non-handled control mice. The PFC response of handled C57BL/10J mice was significantly suppressed compared to the PFC response in non-handled mice while the response of the handled and non-handled BALB/cJ mice was not significantly different.

Hypocholesterolemic effect of triterpene alcohols with soysterol on plasma cholesterol in rats.

To identify the synergistic hypocholesterolemic substance found in soybean oil unsaponifiable matter, rats were fed diets containing various fractions of the unsaponifiable matter prepared by silicic acid column chromatography. The plasma cholesterol level of the group fed the alcohol fraction, which mainly consisted of triterpene alcohols, was significantly lower and the effect was synergistic with soysterol. So the effect of cycloartenol and 24-methylenecycloartanol, which are main constituents of triterpene alcohols in soybean oil unsaponifiable matter, was investigated. Both compounds were prepared from gamma-oryzanol (ferulate) and were added (0.05%) respectively to the experimental diet containing 0.5% cholesterol and 1% soysterol. It was observed that both cycloartenol and 24-methylenecycloartanol in combination with soysterol greatly reduced the plasma cholesterol and enhanced cholesterol excretion. This suggests that the hypocholesterolemic activity of dietary vegetable oils may account for not only their fatty acid compositions and sterol contents but also the synergistic hypocholesterolemic effect of triterpene alcohols.

Age, immunity and the skin.

With advancing age there is a decrease in T-lymphocyte functions leading to defective cell-mediated immune responses and decreased levels of immunoglobulin G, which is produced by B cells under the influence of certain T lymphocytes. Decreased resistance to viruses as a result of the depression of T-cell function may lead to some clinical viral infections which trigger autoimmune diseases. The diminished T cell's immune response and its inability to eliminate ultraviolet-light-damaged epidermal cells may be in part responsible for the increased incidence of skin malignancies in elderly patients.