Heparan sulfate proteoglycan is associated with amyloid plaques and neuroanatomically targeted PrP pathology throughout the incubation period of scrapie-infected mice.

Heparan sulfate proteoglycan (HSPG) has been found to be associated with amyloid deposits in a number of diseases including the cerebral amyloid plaques of Alzheimer's disease and the transmissible spongiform encephalopathies (TSEs). The role of HSPG in amyloid formation and the neurodegenerative pathology of these diseases have not been established. We have addressed these questions using a scrapie mouse model which exhibits both amyloid and nonamyloid deposition of abnormal PrP protein, the protein marker of TSE infection. The distribution of HSPG was examined throughout the course of the disease in the brains of experimentally infected mice and compared with the distribution of abnormal PrP. Abnormally high levels of HSPG were associated with most types of PrP pathology including all plaque types and diffuse neuroanatomically targeted forms. Scrapie-associated HSPG was present from 70 days after infection, the earliest time-point examined, in the same target areas as abnormal PrP. The association with amyloid plaques may indicate that HSPG is involved in amyloid plaque formation and/or persistence but involvement with early diffuse forms of PrP suggests a more fundamental role in scrapie pathogenesis.

Relationships among child abuse, date abuse, and psychological problems.

Data on child abuse, date abuse and psychological problems were gathered from the same participants, 133 female undergraduates, in order to better examine possible relationships among the variables. Verbal abuse in childhood or on dates was examined as well as physical and sexual abuse. Factors influencing whether people remain in or leave abusive relationships were examined, along with possible mediators of the relationships between child abuse, date abuse, and psychological problems. Verbal, physical, and sexual child abuse were all associated with an increased risk of later date abuse or psychological problems. Abuse by a date was also associated with psychological problems. Low self-esteem and anger may have played mediating roles.

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.

Endothelial cells on Dacron vascular prostheses: adherence, growth, and susceptibility to neutrophils.

Human umbilical vein endothelial cells (HUVEC) on knitted and woven Dacron prostheses were compared with HUVEC on smooth surfaces (tissue culture polystyrene, PET film, and Natrix) with regard to adherence, growth, and susceptibility to injury by neutrophils (PMN). These are properties of importance for successful seeding or coating of prostheses. For prosthetic material of given macroscopic dimensions, more endothelial cells (EC) adhered than to smooth surfaces. However, the prostheses had a greater effective surface area as determined by the number of EC at confluency. When this parameter was taken into account, fewer EC were found adherent to prosthetic material per unit effective surface area than for the smooth surface substrates. Growth on prostheses was clearly inferior to that on smooth surfaces, and EC on prostheses were more susceptible to attack by activated PMN than on smooth surfaces. These differences may reflect the topographic differences in cells attached to fibers where they assume more distorted shapes by stretching to span fibers.

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.

Comparison of tissue factor and prostacyclin production by human umbilical vein endothelial cells on Dacron vascular prostheses and Dacron smooth films.

The functional capacity of human umbilical vein endothelial cells (HUVEC) grown on Dacron (polyethylene terephthalate; PET) vascular prosthetic material was compared with the function of cells on smooth surfaced PET, tissue culture polystyrene (TCPS), and Natrix-coated TCPS. Prosthetic materials include two knitted fabrics (Bionit I and II) and two woven preparations (DeBakey Soft Woven and Extra Low Porosity). Two entities produced by HUVEC that influence blood coagulation were assessed: the procoagulant tissue factor (TF) and the anticoagulant prostacyclin (PGI2). Although TF activity was stimulated on all substrates by endotoxin (LPS), there was no difference among prostheses and no difference among smooth surface materials, but TF was reduced in cells on the prosthetic materials relative to those on smooth surface substrates. The reduced TF production by HUVEC on prosthetic material could be reversed by returning them to TCPS. In contrast, PGI2 production on prostheses was comparable to that on smooth surfaces for both stimulated and unstimulated cells. Stimulation with histamine (1 microM) gave a 2.4-fold increase in PGI2 whereas mellitin (10 micrograms/ml) increased production 12.5-fold. The differential response of HUVEC with regard to these two coagulation factors, one of which is secreted and the other membrane bound, may reflect the distorted shape of cells on fibers of the prosthesis.

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.