Amyloidosis: a review of recent diagnostic and therapeutic developments

Amyloid deposition is associated with a diverse range of disorders that includes Alzheimer's disease, type II diabetes mellitus and dialysis arthropathy. Although less common, systemic AA and AL amyloidosis remain important because effective treatments have increasingly become available. The pathology in all forms of amyloidosis involves the extracellular deposition of protein as characteristic fibrillar aggregates which interfere with tissue structure and function. Amyloid fibrils are derived from different unrelated proteins in the different forms of the disease but share many common properties, including the capacity to bind the normal plasma protein serum amyloid P component (SAP). This is the basis for our development of radiolabelled SAP as a nuclear medicine tracer for the diagnosis and quantitative monitoring of amyloid. Serial studies have shown that the deposits are far from inert but are actually turned over quite rapidly in many patients. The treatment of amyloidosis involves supportive measures whilst every effort is made to reduce the supply of the respective fibril precursor protein. Under favourable circumstances further amyloid deposition will be prevented. existing deposits will regress and improvement of organ function will occur. Since this strategy is not always possible or may fail, new approaches to inhibit fibril formation and promote regression of amyloid are being pursued.     

Ethnic conflict and the psychology of liberation in Guatemala, Peru, and Puerto Rico

Ethnic identity and conflict in Guatemala, Peru, and Puerto Rico are complexly embedded within dynamic systems of class- and race-based geopolitics. Whereas overt violence and terror have permeated both Guatemalan and Peruvian societies, overt conflict has undermined Puerto Rican nationhood. Despite similarities among these 3 countries of Hispano-America, there are important particularities that inform psychological theory and practice. This article explores selected contributions of a psychology of liberation informed by indigenous psychologies and reflexive praxis. The challenges these conflicts and their consequences pose to psychologists seeking to work with populations most deeply affected by these social inequalities are analyzed. It concludes with suggestions of how psychology can move toward the development of community-based responses to psychosocial oppression that foster enhanced individual and collective development in a context of social change.     

Effects of cocaethylene on dopamine and serotonin synthesis in Long-Evans and Sprague-Dawley brains

BACKGROUND: Primary liver cancer is an important health problem in Korea, where hepatitis B virus (HBV) infection is prevalent. The authors conducted a prospective cohort study to evaluate the protective effect of HBV vaccination against liver cancer in adults. METHODS: A total of 370,285 males aged > or = 30 comprised the study population. They were clinically free of liver diseases, and had not been vaccinated against HBV at enrolment. The results of HBV surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) marker positivity and those of the vaccination programme which took place during 1985 were used for the construction of the cohort. About 5% (n = 18,914) were HBsAg positive, 78,094 were anti-HBs positive, and 273,277 were negative for both. Among the candidates for HBV vaccination (n = 273,277), 35,934 (13.2%) people had been vaccinated against HBV during 1985. Cases of liver cancer were ascertained by record linkage and from medical records covering 1986-1989. A multivariate log-linear model was used to test statistical significance and to estimate relative risks (RR). RESULTS: The total follow-up period was 1,404,566 person-years, with an average of 3 years and 10 months. A total of 302 incident cases were ascertained. The overall incidence rate of liver cancer was 21.7 per 100,000 person-years. With reference to the incidence level among the unvaccinated and uninfected, the RR of primary liver cancer among the chronically infected and that of the unvaccinated and infected was 18.1 (95% CI: 14.2-22.9) and 0.34 (95% CI: 0.19-0.60), respectively. The RR among the vaccinated group was 0.58 (95% CI: 0.31-1.09). CONCLUSIONS: This study suggested that artificial immunization through HBV vaccination, even in adulthood, reduces the risk of liver cancer. It might also offer a practicable means of primary prevention, especially in areas with hyperendemicity of HBV infection.     

Local synthesis of C3 within the splenic lymphoid compartment can reconstitute the impaired immune response in C3-deficient mice

Mice bearing a disrupted C3 locus (C3-/-) have an impaired Ab response to T-dependent Ags (bacteriophage phiX 174 and nuclear protein-keyhole limpet hemocyanin) characterized by a reduction in number and size of germinal centers and impaired retention of Ag by follicular dendritic cells. To test the importance of C3 synthesized locally within the lymphoid compartment during an immune response to T-dependent Ag, we reconstituted C3-/- mice with wild-type bone marrow of MHC-identical littermates. Engraftment not only restored local C3 synthesis in the spleen, but also rescued the impaired humoral response. The major source of C3 mRNA was MOMA-2+ macrophages localized within the white pulp areas of the spleen. Interestingly, C3 expression is apparently regulated as C3 mRNA was not detected in splenic sections of nonimmune mice. Furthermore, local C3 synthesis by donor macrophages reversed the impaired Ag trapping by splenic follicular dendritic cells in C3-deficient mice.     

Inhibition by the JAK/STAT pathway of IFNgamma- and LPS-stimulated nitric oxide synthase induction in vascular smooth muscle cells

Inducible nitric oxide synthase (iNOS) is induced in many cell types by cytokines and lipopolysaccharide (LPS). Cytokine signal transduction is believed to be mediated primarily through the JAK/STAT pathway. We therefore examined the effects of a JAK2-specific inhibitor, an antisense oligonucleotide to JAK2, and electroporation of neutralizing anti-STAT1 and anti-STAT3 antibodies on IFNgamma- and LPS-stimulated induction of iNOS in vascular smooth muscle cells. Unexpectedly, we found that the JAK/STAT pathway suppresses IFNgamma- and LPS-stimulated iNOS induction in these cells. In contrast, the JAK/STAT pathway appears to have a positive role in iNOS induction in RAW 264.7 macrophages.     

Lipid-assisted microinjection: introducing material into the cytosol and membranes of small cells

The microinjection of synthetic molecules, proteins, and nucleic acids into the cytosol of living cells is a powerful technique in cell biology. However, the insertion of a glass micropipette into the cell is a potentially damaging event, which presents significant problems, especially for small mammalian cells (spherical diameter = 2-15 micron), especially if they are only loosely adherent. The current technique is therefore limited to cells that are both sufficiently large or robust and firmly attached to a substrate. We describe here a modification of the standard technique that overcomes some of the problems associated with conventional microinjection but that does not involve the insertion of a micropipette deep into the cell cytoplasm. Instead, this method depends on lipid fusion at the micropipette tip to form a continuous but temporary conductance pathway between the interiors of the micropipette and cell. This technique thus also provides a novel method of transferring lipids and lipid-associated molecules to the plasma membrane of cells.     

Epidural steroids for treating "failed back surgery syndrome": is fluoroscopy really necessary?

Reaction-times were evaluated in 6 parkinsonian patients and 6 normal control subjects using a simple reaction task and 3 choice reaction tasks of differing complexity. Reaction-times were measured as the time from stimulus onset to the onset of electromyographic activity in the responding muscle. Reaction-time was significantly delayed in patients compared to controls in all tasks, but to a greater extent in the more difficult tasks. The relative magnitude of the change, however, was only 4% in the simple reaction task and 8% in the more difficult choice tasks. These results suggest that the deficit in Parkinson's disease is unlikely to represent a defect in preprogramming as suggested by some investigators. Instead, our results indicate a disturbance in the cerebral processing of the auditory stimuli after their occurrence and prior to the initiation of motor activity.