Alzheimer's disease: the relationship between the density of senile plaques, neurofibrillary tangles and A4 protein in human patients.

The numerical density of senile plaques (SP) and neurofibrillary tangles (NFT) as revealed by the Glees silver method was compared with SP and NFT revealed by the Gallyas method and with amyloid (A4) deposits in immunostained sections in 6 elderly cases of Alzheimer's disease. The density of NFT was generally greater and A4 lower in tissue from hippocampus compared with the neocortex suggesting that A4 deposition was less important than the degree of paired helical filament (PHF) related damage in the hippocampus. The density of Glees SP was positively correlated Gallyas SP weakly correlated with A4 deposit number. A stepwise multiple regression analysis which included A4 deposit and Gallyas SP density and accounted for 54% of the variation in Glees SP density. Hence, different populations of SP were revealed by the different staining methods. The results suggested that the Glees method may stain a population of SP in a region of cortex where both amyloid deposition and neurofibrillary changes have occurred.     

In vitro preactivated human T cells engraft in SCID mice and migrate to murine lymphoid tissues.

Mice with severe combined immunodeficiency (SCID) accept grafts of human T and B lymphocytes derived from resting peripheral blood mononuclear cells (PBMC). We wished to determine whether activated human T cells engraft and migrate into lymphoid tissues in SCID mice. PBMC (50 x 10(6)) activated in vitro in a 4-day mixed lymphocyte culture (MLC) were injected into the peritoneum of 12 SCID mice. In 11 of 12 animals killed at 3 or 4 weeks after injection, human cells were detected in cells pooled from lymphoid organs by flow cytometry and by immunohistochemical staining of frozen tissue sections. The percentage of CD45+ cells in the 11 mice ranged from 2% to 45% and the absolute numbers of CD45+ cells recovered from lymphoid organs ranged from 4 x 10(6) to 90 x 10(6). Up to 93% of the human cells expressed the CD3 antigen together with either CD4 or CD8. Human T cells were localized in periarteriolar areas in murine spleens, whereas in the lymph nodes and gut mucosa, the T cells did not show the pattern for T-dependent areas found in human lymphoid tissue. Numerous human plasma cells were detected in the spleen and gut mucosal crypts of engrafted SCID mice. Human IgG was detected in the serum of all 11 engrafted SCID mice. The functional activity of human T cells recovered from murine splenic tissue was very low 3-4 weeks after engraftment.     

Lone star tick-infecting borreliae are most closely related to the agent of bovine borreliosis

Although Borrelia theileri, the agent of bovine borreliosis, was described at the turn of the century (in 1903), its relationship with borreliae causing Lyme disease or relapsing fever remains undescribed. We tested the previously published hypothesis that spirochetes infecting Lone Star ticks (Amblyomma americanum) may comprise B. theileri by analyzing the 16S ribosomal DNAs (rDNAs) and flagellin genes of these spirochetes. B. theileri, the Amblyomma agent, and B. miyamotoi formed a natural group or clade distinct from but most closely related to that of the relapsing fever spirochetes. B. theileri and the Amblyomma agent were 97 and 98% similar at the nucleotide level within the analyzed portions of the 16S rDNA and the flagellin gene respectively, suggesting a recent divergence. The agent of bovine borreliosis might be explored as a surrogate antigen for the as-yet-uncultivatable Amblyomma agent in studies designed to explore the etiology of a Lyme disease-like infection associated with Lone Star ticks.     

Comparison between testosterone oenanthate-induced azoospermia and oligozoospermia in a male contraceptive study. IV. Suppression of endogenous testicular and adrenal androgens

Administration of supraphysiological doses of testosterone to normal men causes inhibition of spermatogenesis, but while most become azoospermic, 30-55% maintain a low rate of spermatogenesis. We have investigated whether there are differences in endogenous androgen production, of testicular and adrenal origin, which may be related to the degree of suppression of spermatogenesis. Thirty-three healthy Caucasian men were given weekly i.m. injections of 200 mg testosterone oenanthate (TE), 18 became azoospermic, while 15 remained oligozoospermic. Urinary excretion of epitestosterone, a specific testicular product, was reduced to <10% of pretreatment values, with no differences between the groups. Similar results were obtained for other markers of testicular steroidogenesis. Urinary and plasma adrenal androgens were also reduced during TE treatment: a statistically significant decrease in both (P < 0.001 and P < 0.05 respectively) was seen in the azoospermic but not oligozoospermic responders. These results suggest that testicular steroidogenesis is decreased to <10% by the administration of supraphysiological doses of exogenous testosterone. Differences in the degree of ongoing steroidogenesis in the testis do not appear to account for incomplete suppression of spermatogenesis, thus differences in androgen metabolism may underlie this heterogeneous response. A small but significant reduction in secretion of adrenal androgens was also detectable, the relevance of which is unclear.      

Differences in mouse interferons according to cell source and mode of induction.

Mouse interferon induced by ultraviolet-irradiated Newcastle disease virus or polyriboinosinic-polyribocytidylic acid in T lymphocytes, B lymphocytes, macrophages, and primary mouse embryonic cell culture was studied. Irrespective of the inducer, interferons produced by T or B lymphocytes were relatively heat stable and of low antigenicity when reacted with antiserum against L-cell interferon (ALI), whereas interferons produced by macrophages and mouse embryo cells were heat labile and of high antigenicity against ALI. Mouse interferons induced by ultraviolet-irradiated Newcastle disease virus were separated into three components by chromatography on CH-Sepharose 4B. Interferons produced by T and B lymphocytes consisted primarily of component 1 (unbound fraction), whereas interferons produced by macrophages or mouse embryo cells consisted primarily of component 3 (eluted by 0.5 M NaCl). Component 1 was heat stable and of low antigenicity against ALI, properties characteristic of T- and B-cell interferon. Components 2 and 3 were heat labile and of high antigenicity against ALI, properties characteristic of macrophage and mouse embryo cell interferon. In contrast, interferon induced in mice sensitized with BCG differed from these interferons induced in B cells, T cells, macrophages, and fibroblasts in being extremely acid labile and nonreactive against ALI.     

Fc receptors on the surface of Toxoplasma gondii trophozoites: a confounding factor in testing for anti-Toxoplasma antibodies by indirect immunofluorescence.

Negative sera often produce false-positive polar patterns of fluorescence in indirect immunofluorescence tests for serum anti-Toxoplasma gondii antibodies, representing a confounding factor in the diagnosis of toxoplasmosis. In this work, we studied whether T. gondii trophozoites, the antigenic material used in the immunofluorescence tests, expressed surface Fc receptors that could cause the binding of normal immunoglobulins, thus producing false-positive results. We report here that T. gondii trophozoites indeed have Fc receptors on their surface. This was shown by the direct binding of purified human Fc to the parasite, evidenced by the subsequent binding of fluorescein-labeled Fab specific for human Fc. In addition, pretreatment of the parasite with excess purified Fc to saturate the surface Fc-binding sites abrogated the formation of polar fluorescence. The trophozoites appeared to express Fc receptors with different degrees of affinity for the specific ligand, since a diffuse fluorescence pattern was observed following incubation with 1 mg of Fc per ml (10 micrograms per well), whereas with 0.2 mg (0.2 micrograms per well), a majority of parasites showed polar fluorescence. This observation suggests that the Fc receptors accumulated at the polar cap are those with higher affinity. The present findings raise intriguing questions regarding the possible biological role(s) of the Fc receptors on T. gondii but, more immediately, indicated that pretreatment of the antigenic material with Fc, a commercially available reagent, constitutes a practical, simple way to avoid false-positive immunofluorescence test results due to the binding of nonspecific immunoglobulin to the parasite.     

Cystic fibrosis: Synthesis of ciliary inhibitor by amniotic cells

The presence of a ciliary inhibitor in media of cultured amniotic cells obtained from a fetus heterozygous for cystic fibrosis has been observed by the oyster gill cilia assay. The chromatographic fraction containing the inhibitor corresponded to eluted fractions chromatographed from cystic fibrosis fibroblast media and serum. An analogous chromatographic fraction from media of cultured amniotic cells from two proportedly normal fetuses did not inhibit cilia. The chromatographic fraction from media of cultured amniotic cells of a fetus at high risk for cystic fibrosis did not inhibit ciliary activity. Serum was collected from this baby seven weeks after birth and also did not inhibit ciliary action, indicating a homozygous normal genotype. These observations may lead to the development of an antenatal test for cystic fibrosis.