Neuroglial response after induction of experimental allergic encephalomyelitis in susceptible and resistant rat strains

Experimental allergic encephalomyelitis (EAE), the animal model for multiple sclerosis in humans, a T-cell mediated disease of the central nervous system is characterized by inflammatory infiltrates of myelin antigen(s)-specific T cells and consecutive demyelination. Spinal cord tissue emulsified in complete Freund's adjuvant clinical disease in the genetically susceptible Dark Agouti rats (DA) but not in Albino Oxford (AO) rats although similar inflammatory infiltrates in the CNS are observed in both strains 10-12 days after induction. We have shown that the resistance to clinical disease of AO rats is associated with rapid clearance of infiltrating mononuclear cells by a mechanism of apoptosis. Here, we demonstrate by immunohistochemical and FACS analyses of the expression of CD11b/c that microglial cells respond differently to disease induction in the two strains. Whereas microglial cells are activated throughout the period of day 10-28 days after EAE induction in AO rats they are only activated at the inception and resolution phases but not at the peak of clinical disease in DA rats when there is the highest level of CD4+ T cell infiltration. Our findings are compatible with the notion that microglia terminate effector T cells by apoptosis and that lack of this mechanism as evidenced by the lack of CD11b/c expression, support T cell survival and clinical expression of disease.     

Fitness comparison inPhytoseiulus persimilis strains resistant and susceptible to methidathion

The effect of selection for methidathion resistance on fitness components of aP. persimilis strain was analysed by different means. The resistant strain was compared with the susceptible one from which it was selected. The life history and some parameters essential to the successful use of this species in biological control (voracity, resistance to starvation and drought) were analysed. Methidathion resistance was followed for 6 months under rearing conditions free of insecticide in the resistant and in a mixed strain. The investigations showed that the fitness of resistant mites did not seem altered by methidathion selection. It thus appears possible to increase pesticide resistance in beneficial arthropods without adversely affecting their main fitness components.     

赤拟谷盗的磷化氢敏感和抗性品系体内羧酸酯酶的活性比较

本文比较测定了赤拟谷盗Tribolium castaneum(Herbst)的磷化氢抗性(Rf=327)和敏感品系害虫的羧酸酯酶活性,研究了该害虫同一品系不同个体间羧酸酯酶的活性差异,比较了两品系害虫在系列磷化氢浓度下熏蒸24h和6.94×10-2mg/L磷化氢浓度下熏蒸不同时间的羧酸酯酶活性。主要结果为:未熏蒸的抗性害虫幼虫和蛹体内的羧酸酯酶活性分别高于敏感品系的1.37和1.16倍;敏感和抗性害虫同品系内不同个体间羧酸酯酶活性分布频率都存在明显差异,抗性害虫中酶活性大的个体数量占的比例较大;磷化氢浓度分别为0.69×10-2、2.78×10-2、5.56×10-2、8.33×10-2和11.11×10-2mg/L时都可导致敏感害虫羧酸酯酶的活性降低,但活性受抑制的程度不因浓度高低呈相应的增减。浓度分别为5.56×10-2、11.11×10-2、13.89×10-2、20.83×10-2和27.78×10-2mg/L的熏蒸中抗性害虫体内酶活性增加,且活性增高的程度与浓度增减也不呈对应变化。在6.94×10-2mg/L磷化氢浓度下熏蒸不同时间的结果中,敏感害虫的酶活性随时间延长而下降,抗性害虫的活性则随时间延长而增大。研究表明赤拟谷盗对磷化氢的抗性可能与羧酸酯酶的活性增加有关。     

Plasmodium yoelii: antibody response in resistant and susceptible mouse strains

The numbers of antigen-reactive antibody-secreting cells, levels of parasite antigen-specific serum antibodies and numbers of red blood cells staining positive for surface immunoglobulin were determined for susceptible and resistant mouse strains following infection with Plasmodium yoelii 17x. As a control, these parameters also were measured using antigen prepared from normal red blood cells. The relatively susceptible C57BL/6 mice produced more antigen-specific antibody-secreting cells and had higher levels of immunoglobulin positive red blood cells than did DBA/2 mice, but the DBA/2 mice had more antigen-specific IgG in their sera. Both mouse strains possessed cells secreting antibody reactive with soluble normal red blood cell antigen; however, C57BL/6 mice had more IgG positive unparasitized RBC than did DBA/2 mice. Despite possessing fewer antibody positive normal RBC, DBA/2 mice had significantly higher levels of serum antibodies that reacted with soluble red blood cell antigen. These data indicate that levels of serum antibody may not reflect the amounts of antibody produced and that use of any single assay to assess the magnitude of the antibody response may give rise to misleading results.     

Genetically determined variability in rat behavior and its biochemical correlates

Using the combination of extremely high and low values of two independent behavioural variables (activity and frequency of defecation in open field) four groups of rats were selected with different CNS reactivity corresponding to the types of higher nervous activity described by I.P. Pavlov. These groups of rats revealed significant differences in reactivity to stress and drugs, in social behaviour and biochemical pattern. They may represent a useful tool for the research in experimental psychology, neurophysiology, psychopharmacology and other branches of science.     

Congenic strains of mice susceptible and resistant to mouse hepatitis virus.

A congenic strain of C3HSS mice, which is histocompatible with C3H mice but differs from them in susceptibility to mouse hepatitis virus (MHV), has been developed by introducing the gene for susceptibility to the MHV-PRI virus from the PRI mice. This was accomplished by continual back-crossing of the hybrids to the C3H mice, but at the same time by selection of susceptibility by use of macrophage culture tests. After 20 back-crosses, a strain homozygous for susceptibility was produced by brother-sister mating of individual mice whose potential for carrying the recessive gene for resistance was tested in progeny. Since the original choice of mice for breeding was based on in vitro macrophage susceptibility, and since highly susceptible mice were developed on the same basis, it seems evident that macrophage susceptibility is an integral aspect of mouse susceptibility. The continued production of almost 50% susceptible mice in the back-crosses is further evidence of the dominant one-locus explanation of genetic susceptibility to this agent. Incomplete penetrance may also be present in 8 and 9 week old mice of the C3HSS strain since there was a sharp decrease in susceptibility of these mice even though their macrophages in culture maintained full susceptibility.     

Theiler's virus induces the MIP-2 chemokine (CXCL2) in astrocytes from genetically susceptible but not from resistant mouse strains

The murine encephalomyelitis virus of Theiler (TMEV) induces demyelination in susceptible strains of mice by a CD4(+) Th1 T cell mediated immunopathologic process. We focused on the production of one chemokine, the macrophage inflammatory protein-2 (MIP-2 or CXCL2), by cultured mouse astrocytes infected with the BeAn strain of TMEV. Analysis of a murine genome DNA hybridized with cRNA from mock- and TMEV-infected astrocytes, revealed up-regulation of three sequences encoding MIP-2. Northern blot analysis indicated increased MIP-2 mRNA expression. Levels of MIP-2 in the supernatants of infected cells as detected by ELISA, varied directly with the multiplicity of infection used. This secreted CXCL2 was biologically active inducing chemoattraction of neutrophils but not of lymphocytes. CXCL2 was specifically induced by TMEV infection, since induction was inhibited by anti TMEV antibodies. The inflammatory cytokines, IL-1alpha and TNF-alpha, which are also induced in astrocytes by TMEV, were very potent inducers of CXCL2. Nevertheless, both mechanisms of induction follows different pathways as antibodies to both cytokines fails to inhibit TMEV-induced CXCL2 up-regulation. Sera from TMEV-infected SJL/J mice with chronic demyelination, but not from BALB/c TMEV-resistant mice, revealed CXCL2 at the peak of clinical disease. Our main novel finding is the strain-dependent differences in CXCL2 expression both in vitro and in vivo. This suggest an role for this chemokine in attracting immune cells within the CNS, which in turn, might trigger demyelination in this experimental model of MS.     

Gene expression changes in the host response between resistant and susceptible inbred mouse strains after influenza A infection

Inbred mouse strains exhibit differences in susceptibility to influenza A infections. However, the molecular mechanisms underlying these differences are unknown. Therefore, we infected a highly susceptible mouse strain (DBA/2J) and a resistant strain (C57BL/6J) with influenza A H1N1 (PR8) and performed genome-wide expression analysis. We found genes expressed in lung epithelium that were specifically down-regulated in DBA/2J mice, whereas a cluster of genes on chromosome 3 was only down-regulated in C57BL/6J. In both mouse strains, chemokines, cytokines and interferon-response genes were up-regulated, indicating that the main innate immune defense pathways were activated. However, many immune response genes were up-regulated in DBA/2J much stronger than in C57BL/6J, and several immune response genes were exclusively regulated in DBA/2J. Thus, susceptible DBA/2J mice showed a hyper-inflammatory response. This response is similar to infections with highly pathogenic influenza virus and may serve as a paradigm for a hyper-inflammatory host response to influenza A virus.     

Characterization of 7-ethoxycoumarin-O-deethylase from malathion resistant and susceptible strains of Drosophila melanogaster

Mixed-function oxidase activity in a D. melanogaster strain carrying at least two closely linked malathion resistance genes on chromosome 3 was compared with the susceptible Canton S strain. The kinetics of O-deethylation of 7-ethoxycoumarin (7-ECD activity) with respect to pH, temperature, substrate and cofactor (NADPH) affinities and the response to metal salts of both strains were similar. The resistant strain had approx. 5-fold greater 7-ECD specific activity, and a parallel increase in total cytochrome P-450 content. Developmental stage, sex and nutritional state affected Drosophila 7-ECD activity. The intestine, fat body and Malpighian tubules contained the largest 7-ECD specific activity. Both susceptible and resistant strains had similar patterns of 7-ECD expression and differed only in total activity. In addition to more cytochrome P-450, the resistant strain had increased amounts of two microsomal, heme-staining polypeptides (M_r = 50 and 54 K after SDS-PAGE). The results suggest that the genetic change in the resistant strain involves the regulation of the Drosophila cytochrome P-450 system.     

The reactions of susceptible and resistant tomato cultivars to strains of Verticillium albo-atrum

Three strains of Verticillium albo-atrum causing severe wilt of tomato (T), progressive (Hp ) and fluctuating (HF) wilt of hop, were inoculated through the roots of four tomato cultivars at different inoculum concentrations. Symptoms were assessed visually 42 days after inoculation, and quantitatively on the change in total leaf area compared with controls. Distribution of mycelium and tyloses was determined by sections at 2 cm intervals of root, stem and petiole. Cultivars Loran Blood and Moscow showed resistance to disease expression at all levels of inoculum concentration with the T strain. Bonny Best and Potentate were both susceptible to this strain, but whereas in Potentate, disease severity increased from mild to severe with increase in inoculum concentration, Bonny Best was severely diseased at the lowest level of inoculum. All cultivars showed some susceptibility to the HP and HF strains; the ‘resistance’ of Loran Blood and Moscow was no longer apparent and Bonny Best was most severely affected. The relative susceptibilities to the strains were HF Bonney Best > Loran Blood > Potentate > Moscow, HP Bonny Best > Loran Blood, Moscow > Potentate, T Bonny Best > Potentate > Loran Blood, Moscow. In general, vascular colonization was less in the cultivars Loran Blood and Moscow with all three fungal strains at io⁵propagules/ml level of inoculum, but this was not always correlated with an increase in disease severity. With the exception of the host-pathogen combinations Bonny Best/T, Bonny Best/HF, Potentate/T and Moscow/T, increasing the inoculum concentration to 10⁷propagules/ml increased disease severity but had little or no effect of increasing vascular colonization. In Bonny Best/T, Bonny Best/HF and Potentate/T vascular colonization was reduced with the higher level of inoculum. Moscow showed complete resistance to symptom expression and little vascular colonization with the T strain at 10⁵prop./ml. At 10⁷prop./ml resistance was maintained but there was very extensive growth of mycelium in the vessels. Tylosis resulted from an interaction of host, fungal strain and the level of inoculum and was not always correlated with the degree of vascular colonization. Contrary to previous reports the resistant varieties Loran Blood and Moscow developed acute disease symptoms after inoculation with HP and HF and these were associated with a high level of tylosis rather than mycelial growth. Tylosis and disease severity but not mycelial growth increased with higher levels of inoculum. The results suggested that susceptibility to Verticillium wilt was a complex response depending on host cultivar, fungal strain and the initial inoculum concentration. In some cultivar-pathogen combinations susceptibility was directly proportional to the amount of mycelium present in the vessels, while in others a physiological resistance mechanism independent of the degree of colonization appeared to operate. In a third category, increased disease development rather than resistance was associated with high levels of tylosis.     

Pathogenesis of street rabies virus infections in resistant and susceptible strains of mice.

Seven strains of mice were examined to determine why susceptibility differences and variations in clinical central nervous system (CNS) disease occurred among these animals after intraperitoneal inoculation of street rabies virus (SRV). Trace experiments for infectious virus indicated that these differences were associated with restriction of virus replication within the CNS. Limitation of viral replication appeared to correlate with the antibody response in that prominent serum anti-SRV neutralizing antibody titers were detected in resistant strains, whereas susceptible strains produced minimal amounts of antibody until their death. The importance of the immune response was reaffirmed with cyclophosphamide studies in that all resistant SJL/J mice died after immunosuppressive treatment. In contrast, cyclophosphamide-treated SJL/J mice whose immune systems were reconstituted with either unfractionated immune spleen cells or with sera 24 h after SRV inoculation survived a lethal dose of SRV. More importantly, immunosuppressed SJL/J and immunodeficient athymic mice were protected when reconstituted with immune serum 72 h after SRV inoculation, a time in which infectious virus was detected in the spinal cords of some mice but was not present in the peritoneal cavity. Additional studies showed that antibody in the cerebrospinal fluid was unimportant in the resistance of mouse strains which remained clinically asymptomatic, but it appeared to be associated with the survival of mice which developed clinical CNS disease. Furthermore, CNS resistance to intranasal or intracerebral inoculation with challenge virus standard rabies virus developed as early as 5 days post-intraperitoneal inoculation of SRV.     

An ultrastructural investigation of Leishmania donovani infection in genetically resistant and susceptible mouse strains

Natural resistance to the growth of Leishmania donovani in mice is controlled by a gene (Lsh) which is expressed, in an unknown fashion, in macrophages. Early net growth rate of the parasite is much higher in mice strains bearing the susceptible allele (Lshs) than in resistant (Lshr) mice. Intracellular events occurring in the Kupffer cells during this period have been studied at the ultrastructural level. It was found that the number of dividing amastigotes per thin section of infected cell was approximately 10-fold greater in susceptible (B10.A SgSn) than in resistant (A/J) strains of mice, both 7 and 14 days following infection. These findings support the hypothesis that high natural resistance to leishmaniasis (Lshr) is expressed as a microbistatic effect, exerted within the parasitized macrophage of the host.     

Pathogenesis of acute murine cytomegalovirus infection in resistant and susceptible strains of mice.

We have characterized the progress of acute murine cytomegalovirus (MCMV) infection in the spleen, liver, and salivary gland of susceptible (BALB/c) and resistant (C3H) strains of mice after intraperitoneal inoculation. Viral replication was analyzed by virus titration, infectious-center assays, and in situ cytohybridization with cloned subgenomic fragments of the MCMV genome. The most striking differences between strains were observed in the spleen. At 24 h postinfection (p.i.), both strains had a similar number of infected spleen cells. At 48 h p.i., BALB/c mice showed marked dissemination of the splenic infection which continued until 96 h p.i. In contrast, the number of infected C3H spleen cells did not increase from the 24-h level but declined later on. This early block in dissemination of MCMV infection in C3H mouse spleens was not a result of the H-2k haplotype, as BALB.K (H-2k) mice, which show an intermediate level of resistance to MCMV infection, exhibited dissemination of the infection between 24 and 48 h p.i., albeit at a reduced level. However, between 72 and 96 h p.i., we observed a decline in the number of infected spleen cells in BALB.K mice similar to that observed in C3H mice. We also demonstrated by Southern blot analysis of DNA from the infected spleen cells that the termini of the MCMV genome fuse after in vivo infection.     

桃蚜抗吡虫啉品系和敏感品系某些生物学特性比较

室内连续筛选15代,桃蚜Myzuspersicae(Sulzer)对吡虫啉产生了一定水平的抗性,抗性倍数是14.34倍。通过建立抗性品系和敏感品系的生命表,比较了抗性品系和敏感品系的发育历期和生殖力的差异。结果表明,抗性品系适合度显著下降,若蚜存活率降低,若蚜历期延长,成蚜寿命缩短;在繁殖上表现为产仔量下降,生殖期缩短。以净生殖率(Ro)和内禀增长率(rm)来评价抗性品系的相对生物适合度,与敏感品系相比,吡虫啉抗性品系的相对适合度分别为0.699和0.897。