Protease-resistant PrP deposition in brain and non-central nervous system tissues of a murine model of bovine spongiform encephalopathy.

Infectivity within the central nervous system has been demonstrated by the transmission of bovine spongiform encephalopathy (BSE) from affected cattle to inbred laboratory mice. Sedimentable, protease-resistant PrP (PrPSc) has also been extracted from BSE-affected cattle brain. Both infectivity and PrPSc have been reported in the lymphoreticular tissues of sheep and mice clinically and preclinically affected with scrapie. Neither infectivity nor PrPSc has yet been detected in non-neural tissues of naturally occurring, clinical cases of BSE in cattle. We have used a murine model of BSE (301V isolate in VM/Dk mice) to investigate when and where PrPSc accumulates. PrPSc was detected both in brain and in extraneural sites prior to the onset of clinical symptoms. This murine BSE model differs, however, in four important aspects from our previously published findings for murine scrapie models: (a) PrPSc was found relatively late into the incubation period; (b) after intracerebral inoculation, PrPSc was found in brain before it was found in other tissues; (c) no PrPSc was found in most of the spleens from clinically affected animals after intracerebral inoculation; and (d) even after intraperitoneal infection, PrPSc was detected in brain first.

Social evaluation and cardiovascular response: an active coping approach.

Cardiovascular effects of social evaluation were examined under different task conditions. In Experiment 1, systolic responses in women were greater under public than private conditions when a fixed behavioral challenge was difficult, but not when the challenge was easy. In Experiment 2, social evaluation potentiated systolic responsivity in men and women when a behavioral challenge was unfixed, but not when a behavioral challenge was fixed and easy to meet. Results are discussed in terms of a recent integrative analysis of effort and cardiovascular response as well as alternative conceptions that posit, or might be taken to imply, an association between publicity and physiologic activation.

Effect of Sinc genotype, agent isolate and route of infection on the accumulation of protease-resistant PrP in non-central nervous system tissues during the development of murine scrapie.

Mice congenic for the Sinc gene were infected intracerebrally with two scrapie strains, ME7 and 22A. At various times during the incubation period tissues were monitored for the infection-specific form of PrP (PrPSc). PrPSc was found in brain, spleen, lymph nodes, pancreas, submaxillary gland and thymus. After intraperitoneal inoculation PrPSc was found in spleen, lymph nodes, pancreas and submaxillary glands prior to its detection in brain. The kinetics of accumulation of PrPSc in these tissues was dependent on the infecting strain of agent, on the mouse Sinc genotype and on the route of infection. This study supports using the presence of PrPSc as an indicator of infectivity in brain and extraneural tissues and defines some of the parameters which influence when and where PrPSc is first found.

Pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG) and various acute phase reactants in rheumatoid arthritis and osteoarthritis.

Pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG) concentrations have been measured in matched sera and synovial fluid samples obtained from 36 patients with rheumatoid arthritis and 10 patients with osteoarthritis. Levels of alpha 2-PAG in serum and synovial fluid were significantly higher in rheumatoid arthritis than in osteoarthritis. Calculation of the synovial fluid/serum ratios for alpha 2-PAG gave results which are explicable only if this protein were being synthesised locally. In a longitudinal study of 15 patients with rheumatoid arthritis, concentrations of alpha 2-PAG did not reflect disease activity, unlike those of the classical acute phase reactants, C-reactive protein and caeruloplasmin.

The effect of human alpha 2-macroglobulin on the restoration of humoral responsiveness in x-irradiated mice.

The effect of human alpha 2-macroglobulin on the recovery of the humoral immune response in X-irradiated mice has been assessed by measurement of antibody-forming cells in the spleen 5 days after challenge with sheep erythrocytes. The capacity of this protein to promote the recovery of immune responsiveness was variable, and appeared to be influenced by the strain and sex of the mice, and the dose of alpha2M given.

The association of alpha2-macroglobulin with lymphocyte membranes in chronic lymphocytic leukaemia and other disorders.

The association of alpha2-macroglobulin (alpha2M) with the surface membranes of human peripheral blood lymphocyte preparations has been investigated by the direct immunofluorescent technique. The percentage (and total number) of lymphocytes with detectable alpha2M on their surface is significantly increased in chronic lymphocytic leukaemia. The incidence of alpha2M-positive cells in normal and pathological conditions closely parallels that observed with conjugated antiserum to the kamma and gamma light chains of human immunoglobulin. It bears no relationship however to the plasma alpha2M levels or to the age of the donor. Additional blocking studies with aggregated human IgG, soluble antigen-antibody complexes and the F(ab')2 moiety of the anti-alpha2M, and indirect immunofluorescent studies with the latter, indicate that the fluorescence observed is not due to interaction of the conjugated reagent with Fc or C3 receptors.

Normal and pathological serum levels of alpha2-macroglobulins in men and mice.

The serum levels of alpha2-macroglobulin have been measured in normal men and mice and in a number of immunopathological conditions. Normal human concentrations are high in youth, reach their minimum in middle age, and gradually increase with old age. In all age groups the mean is higher in the female than in the male. Conversely, in normal mice the alpha2M level is low in youth, maximum in middle age, and shows a slight depression with old age, and the levels are frequently higher in males than in females; there are also strain variations. In human immunopathological conditions, there are some deviations from the normal alpha2M level but these are seen to be changes from the normal distribution of values around the mean, rather than significant elevation or depression of mean values. In some disease states studied there are differences between the sexes in the deviation from normal. "Abnormal" strains of mice had alpha2M levels within the range exhibited by "normal" mice but changes in the levels are seen in mice with various myelomas.