Risk of AIDS related complex and AIDS in homosexual men with persistent HIV antigenaemia.

One hundred and ninety eight men seropositive for human immunodeficiency virus (HIV) antibody and 58 HIV antibody seroconverters were studied for an average of 19.3 (SEM 0.5) months to assess the relation between HIV antigenaemia and the risk of developing the acquired immune deficiency syndrome (AIDS) and AIDS related complex. Forty (20.2%) of the 198 HIV antibody seropositive men were antigen positive at entry and remained so during follow up. Eight (13.8%) of the 58 HIV antibody seroconverters and 20 (12.7%) of the remaining 158 HIV antibody seropositive men became antigen positive during follow up, resulting in an end point attack rate for HIV antigenaemia of 14.3%. AIDS related complex was diagnosed in 25 (15.8%) of the HIV antigen negative men and in 14 (20.7%) of the HIV antigen positive men. AIDS was diagnosed in 15 men, resulting in an end point attack rate for AIDS of 23.9% in the HIV antigen positive group and 1.3% in the antigen negative group. HIV antibody seropositive men without symptoms but with persistent HIV antigenaemia are at increased risk of developing AIDS and AIDS related complex.     

Hemorrhage in mice produces alterations in B cell repertoires

Multiple organ system failure secondary to infection is the major cause of late deaths after trauma and hemorrhage. The production by B cells of antibodies directed against bacterial antigens is an important component of host defenses. In order to determine the effects of hemorrhage on B cell function, we examined hemorrhage-induced alterations in available (clonal precursors) and actual (plasma cells) B cell repertoires in the course of an immune response toward bacterial antigens. Hemorrhage produced greater than twofold decreases in the absolute frequency and number of clonal precursors specific for the bacterial antigens dextran, levan, and pneumococcal polysaccharide type II. After blood loss, there were decreases in absolute frequency, but not in numbers, of clonal precursors capable of producing antibodies against the nonbacterial antigens ovalbumin and mouse transferrin. Immunization with the bacterial antigen levan within 24 hr of hemorrhage resulted in approximately 50% fewer levan-specific plasma cells than that seen in normal, unhemorrhaged mice. These results demonstrate that hemorrhage produces marked alterations in B cell repertoires, which may contribute to postinjury abnormalities in host defenses.     

Two major classes of mitogen-reactive B lymphocytes defined by life span

The relative numbers of short- and long-lived mitogen-reactive B cells in the peripheral pool were evaluated by studying the decay of lipopolysaccharide (LPS)-reactive B lymphocytes in LPS nonresponder, histocompatible hosts for periods of up to 3 wk after cell transfer. The results obtained demonstrate the existence of two major classes of mitogen-reactive B cells defined by life span. The "short-lived" cell component comprises about 80 to 90% of the reactive cells and decays with a life expectancy of 18 to 24 hr. The long-lived cell component, with life expectancies of 10 to 20 days, comprises about 10 to 20% of the reactive cells and is preferentially enriched in circulating B cells. The present ratio for short- and long-lived B cells implies a highly dynamic state for the immune system which must be advantageous in the selection of available repertoires.     

Life span of B lymphocytes: the experimental basis for conflicting results

Recent claims have challenged the view that most peripheral, mature B cells are long-lived, and propose rates of peripheral decay that are compatible with bone marrow production. This disagreement can only reflect differences in the protocols and methods used to measure peripheral lymphocyte life spans. We have now assessed toxic or other nonselective effects of hydroxyurea treatment on the survival and migration of peripheral, noncycling cells, as well as possible reasons for exaggerated decays of LPS-reactive B cells transferred to LPS nonresponder hosts, the two methods leading to conclusions of short life spans. We also studied general effects on cell survival introduced by either repeated [3H]thymidine injections or the stress associated with surgery, thoracic duct cannulation in particular--methods with which the notion of long life spans had been established. The results failed to show toxic or nonselective effects of hydroxyurea treatments and artificial decays of LPS-reactive cells in adoptive hosts. In contrast, the present experiments demonstrate that both the stress associated with surgery and repeated [3H] thymidine administration profoundly deplete a pool of short-lived B cells, consequently selecting for an apparent higher proportion of long-lived cells.     

Linkage disequilibrium analysis in Machado-Joseph disease patients of different ethnic origins

Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar degeneration originally described in families of Portuguese-Azorean ancestry. The hypothesis that its present world distribution could result from the spread of an original founder mutation has been raised. To test this possibility we have conducted a linkage disequilibrium study of markers segregating with the MJD1 locus in a total of 64 unrelated families of different geographical origins. Significant association was detected between the MJD1 locus and marker alleles at loci D14S280, D14S1050 and D14S81. All affected individuals, except one Chinese family, had allele 3 (237 bp) at D14S280. This finding is consistent with a founder effect in our MJD population. However, distinct haplotypes were observed in patients originating from the two Azorean islands showing the highest disease prevalence; therefore, the possible existence of more than one founder mutation can not be excluded with the markers currently available. Received: 27 February 1996 / Revised: 4 June 1996     

Chemical composition and larvicidal activity of essential oils of three Artemisia species

Aedes aegypti L. (Diptera: Culicidae) is a vector for serious diseases in tropical regions. This pest is mainly controlled by commercial larvicides but the application of such products has led to environmental problems. Essential oils (EO) have been consistently reported as molecules with insecticidal activity and can be used to produce more environmentally friendly larvicides in the control of A. aegypti. In this study, the larvicidal effect of essential oils (EO) from the leaves of three Artemisia species was evaluated against A. aegypti. The oils were obtained from steam distillation and their chemical composition was determined by gas chromatography–mass spectrometry. The EO of Artemisia camphorata was the most active in the screening bioassay and presented LC₅₀ and LC₉₅ of 64.95 and 74.18 μg ml⁻¹, respectively. In addition, we found that germacrene D-4-ol was the constituent responsible for the toxicity of this EO. Artemisia camphorata EO and its major constituent, germacrene D-4-ol, are promising for the development of natural larvicides against A. aegypti.     

The novel flightless-I gene brings together two gene families, actin- binding proteins related to gelsolin and leucine-rich-repeat proteins involved in Ras signal transduction

The Drosophila melanogaster gene flightless-I, involved in gastrulation and muscle degeneration, has Caenorhabditis elegans and human homologues. In these highly conserved genes, two previously known gene families have been brought together, families encoding the actin- binding proteins related to gelsolin and the leucine-rich-repeat (LRR) group of proteins involved in protein-protein interactions. Both these gene families exhibit characteristics of molecular changes involving replication slippage and exon shuffling. Phylogenetic analyses of 19 amino acid sequences of 6 related protein types indicate that actin- associated proteins related to gelsolin are monophyletic to a common ancestor and include flightless proteins. Conversely, comparison of 24 amino acid sequences of LRR proteins including the flightless proteins indicates that flightless proteins are members of a structurally related subgroup. Included in the flightless cluster are human and mouse rsp-1 proteins involved in suppressing v-Ras transformation of cells and the membrane-associated yeast (Saccharomyces cerevisae) adenylate cyclase whose analogous LRRs are required for interaction with Ras proteins. There is a strong possibility that ligands for this group could be related and that flightless may have a similar role in Ras signal transduction. It is hypothesized that an ancestral monomeric gelsolin precursor protein has undergone at least four independent gene reorganization events to account for the structural diversity of the extant family of gelsolin-related proteins and that gene duplication and exon shuffling events occurred prior to or at the beginning of multicellular life, resulting in the evolution of some members of the family soon after the appearance of actin-type proteins.      

Trehalase activity and its regulation during growth of Saccharomyces cerevisiae.

Trehalase activity decreased in 95% at the onset of the transition phase of growth of S. cerevisiae. The question which we raised was whether this phenomenon was due to proteolysis or to conversion of the enzyme to a less active form (dephosphorylation). Immunological methods allowed to identify the presence of the trehalase protein during cell growth. At the same stage of growth, an increase in the non-phosphorylated enzyme was detected "in vitro". Results utilizing mutant strains also indicated that regulation occurred by interconversion of forms. The same mechanism also seems to control trehalase activity in non proliferating conditions.