Brain Parenchymal and Microvascular Amyloid in Alzheimer's Disease

Brains of patients with Alzheimer disease/senile dementia of Alzheimer type (AD/SDAT) develop a progressive accumulation of amyloid, which deposits primarily in the form of characteristic parenchyma!'plaques' (senile or neuritic plaques/SP's) and as mural deposits in the walls of capillaries and arterioles (cerebral amyloid angiopa-thy/CAA). A major component of this amyloid is a small and unique peptide composed of 39–43 amino acids, beta/A4, which is cleaved from a much larger precursor protein (APP) that has several isoforms. Brain amyloid can be detected in autopsy or biopsy brain tissue by classical, immunohistochemical and ultrastructural (including immuno-electron microscopic) methods of varying sensitivity and specificity. Beta/A4 amyloid deposition is remarkably variable (e.g. predominantly parenchyma! or vascular, or a mixture of parenchymal and vascular) among patients with AD/SDAT. Despite its abundance in the brains of AD/SDAT patients, the precise role of beta/A4 in the pathogenesis of the neurological deficit, neocortical atrophy and progressive synapse loss associated with AD/SDAT has yet to be determined. However, mutations in the gene that encodes APP are clearly associated with familial AD syndromes in which there is significant brain amyloid deposition. CAA, in addition to its association with AD/SDAT, can result in hemorrhagic and (possibly) ischemic forms of stroke. Work with recently developed transgenic mice which express large amounts of beta/A4 in the central nervous system is likely to elucidate mechanisms by which the protein is selectively deposited in the brain in a parenchymal or microvascular form, and how it contributes to the pathogenesis of neurodegeneration.     

Immunochemical cross-reactivity between the dissociated capsid proteins of PVY group plant viruses

Primary (4–5-week) and long-term (12-week) antisera were elicited against the pyrrolidine-dissociated capsid proteins (D-proteins) of tobacco etch virus (TEV) and potato virus Y (PVY), and subsequently used to ascertain the degree of immunochemical cross-reactivity between several PVY group viral D-proteins. Primary antisera were highly specific for homologous antigen. However, immunodiffusion and cross-absorption experiments with long-term anti-TEV D-protein and anti-PVY D-protein sera revealed pronounced cross-reactivity among the D-proteins of 14 different PVY group viruses. Furthermore, all cross-reactions involved the same antibody population except in the case of celery mosaic virus (CeMV) D-protein where but a portion of the antibody population was reactive. Spur formation in immuno-diffusion experiments was only observed among heterologous D-proteins when they were either adjacent to homologous D-protein antigen or (in an opposite direction) when compared with CeMV D-protein. Wheat streak mosaic virus dissociated protein, in contrast, was not found to be cross-reactive with PVY group D-proteins in reciprocal tests, and no cross-reactions were observed with the dissociated proteins of 6 additional viruses outside the PVY group.     

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.      

Purging of acute myeloid leukemic cells by ether lipids and hyperthermia

Ether lipids (EL) and hyperthermia have been shown to possess a relatively selective cytotoxicity to leukemic cells. In this study, the combined effects of EL (ET-18-OCH3, ET-16-NHCOCH3, or BM 41.440) and hyperthermia on the growth of hematopoietic progenitors, myeloid leukemic cell lines, and leukemic cells obtained from patients with acute myeloid leukemia (AML) were examined to determine if this combination resulted in a greater selective killing of leukemic cells than that achieved by either EL or heat alone. When the cells were treated simultaneously with EL (50 micrograms/mL) and hyperthermia (42 degrees C) for one hour, the killing of leukemic cell line cells was enhanced considerably. Among the three EL, however, the combination of ET-18-OCH3 and heat seemed to be the most cytotoxic to leukemic cell line cells with no effect on the growth of hematopoietic progenitors. An increase in the duration of treatment with ET-18-OCH3 to four hours with heat added during the last hour resulted in a further reduction of leukemic cell line cells while sparing 50% of hematopoietic progenitors after cryopreservation. The combined treatment with ET-18-OCH3 and heat also inhibited the growth of leukemic progenitors obtained from AML patients by 97% to 100%. These data indicate that the combined treatment with EL and hyperthermia might offer an efficient means to eliminate myeloid leukemic cells in vitro.     

Schistosoma mansoni Morbidity among School-Aged Children: A SCORE Project in Kenya

Schistosomiasis control programs aim to reduce morbidity but are evaluated by infection prevalence and intensity reduction. We present baseline cross-sectional data from a nested cohort study comparing indicators of morbidity for measuring program impact. Eight hundred twenty-two schoolchildren 7–8 years of age from Nyanza Province, Kenya, contributed stool for diagnosis of Schistosoma mansoni and soil-transmitted helminths (STH) and blood smears for malaria, and were evaluated for anemia, quality of life, exercise tolerance, anthropometry, and ultrasound abnormalities. Schistosoma mansoni, STH, and malaria infection prevalence were 69%, 25%, and 8%, respectively. Only anemia and S. mansoni infection (adjusted odds ratio [aOR] = 1.70; confidence interval [CI] = 1.03–2.80), and hepatomegaly and heavy S. mansoni infection (aOR = 2.21; CI = 1.19–4.11) were associated. Though anemia and hepatomegaly appeared most useful at baseline, additional morbidity indicators may be sensitive longitudinal measures to evaluate schistosomiasis program health impact.