Differences between T cell epitopes recognized after immunization and after infection

Evidence suggests that cellular immune responses play a crucial role in the control of HIV and SIV replication in infected individuals. Several vaccine strategies have therefore targeted these CD8(+) and CD4(+) responses. Whether vaccination induces the same repertoire of responses seen after infection is, however, a key unanswered question in HIV vaccine development. We therefore compared the epitope specificity induced by vaccination to that present postchallenge in the peripheral blood. Intracellular cytokine staining of PBMC stimulated with overlapping 15/20-mer peptides spanning the proteins of SIV were measured after DNA/modified vaccinia Ankara vaccination of eight rhesus macaques. Lymphocytes from 8 animals recognized a total of 39 CD8 epitopes and 41 CD4 epitopes encoded by the vaccine. T cell responses were again monitored after challenge with SIVmac239 to investigate the evolution of these responses. Only 57% of all CD8(+) T cell responses and 19% of all CD4(+) T cell responses present after vaccination were recalled after infection as measured in the peripheral blood. Interestingly, 29 new CD8 epitopes and 5 new CD4 epitopes were recognized by PBMC in the acute phase. These new epitopes were not detected after vaccination, and only some of them were maintained in the chronic phase (33% of CD8 and no CD4 responses). Additionally, 24 new CD8 epitopes and 7 new CD4 epitopes were recognized by PBMC in the chronic phase of infection. The repertoire of the immune response detected in the peripheral blood after immunization substantially differed from the immune response detected in the peripheral blood after infection.     

GH after baclofen and diazepam

It has been proposed that GABAergic receptors possess two functionally distinct, but strictly co-operating binding sites, one for GABA itself, another for benzodiazepines. The activation of GABA receptor is followed by opening of the Cl- channels. This action is strengthened if both binding sites of GABA receptor are contemporaneously engaged by their respective agonists. Baclofen, a GABAergic drug, is able, in acute administration, to determine an increase of serum GH in man. The aim of this work was to control if benzodiazepines can strengthen this metabolic effect of Baclofen in vivo. Five healthy voluntary women were studied. Blood samples for serum GH evaluation were collected basally and 30, 60, 90, 120, 150, 180, 210 minutes after oral administration of 20 mg. of Baclofen. This test was repeated one week after oral administration of 12 mg. die of Diazepam. The results were analyzed for paired data. The finding show that the metabolic effect of Baclofen on GH secretion are prolonged in time after Diazepam premedication and suggest that GABA-benzodiazepines interaction is effective at hypothalamo-hypophyseal level in man.     

Before and after therapeutic abortion

Surveys conducted after therapeutic abortion were used to evaluate contraceptive use, to assess early physical and emotional effects and to provide feedback to the hospital nurses on their counselling role. The follow-up rate was only 53%. Of those who cooperated 82.9% were using effective contraception three months after abortion. Subjective morbidity was greater than anticipated. The main emotional response was relief coupled with some guilt and depression in a significant minority. The occurrence and significance of the after effects of abortion should be explained in advance. Training workshops for abortion counsellors would be useful. The surgical termination of pregnancy is only a small part of a comprehensive abortion service.     

Rehabilitation after falls and fractures

Falls are one of the most common geriatric problems threatening the independence of older persons. Elderly patients tend to fall more often and have a greater tendency to fracture their bones. Fractures occur particularly in osteoporotic people due to increased bone fragility, resulting in considerable reduction of quality of life, morbidity, and mortality. This article provides information for the rehabilitation of osteoporotic fractures pertaining to the rehabilitation of the fractured patient, based on personal experience and literature. It also outlines a suggested effective and efficient clinical strategy approach for preventing falls in individual patients.     

Trees before and after Darwin

Phylogenetic trees published before Darwin’s On the Origin of Species are scarce. Lamarck (1809) and Barbançois (1816; J Phys Chim Hist Nat Arts 82, 444) are the first and only trees devoted to illustrating the genealogical connections between organisms of different species and different higher taxa. In the late 18th and early 19th centuries, most of the trees depicted in papers dealing with natural history were classifications; classifications in the shape of trees, but classifications nonetheless. Those published by Bronn (1858) are a good example. After Darwin, phylogenetic trees incorporating the time dimension flourished. In the first half of the 20th century, the Modern Synthesis failed to renew and rejuvenate the intuitive construction of trees. It wasn’t until the appearance of Hennig’s phylogenetic systematics that the real nature of the connection between phylogeny and the pre‐Darwinian concept of homology was made clear.     

The shape of caveolae is omega-like after glutaraldehyde fixation and cup-like after cryofixation

Caveolae were defined as flask- or omega-shaped plasma membrane invaginations, abundant in adipocytes, fibroblasts, endothelial and smooth muscle cells. The major protein component of caveolar membranes is an integral membrane protein named caveolin. We compared the freeze-fracture behavior of caveolae in glutaraldehyde-fixed and cryofixed mouse fibroblast cells and found distinct differences. In glutaraldehyde-fixed cells almost all caveolae were cross-fractured through their pore and only very few caveolar membranes were membrane-fractured. We found the reverse situation in rapid frozen cells without any chemical fixation where most of the caveolae were membrane-fractured, showing different degrees of invagination from nearly flat to deeply invaginated. In ultrathin sections of glutaraldehyde-fixed heart endothelial cells, caveolae exhibit the well known omega-like shape. In high-pressure frozen, freeze-substituted and low temperature embedded heart endothelial cells, the caveolae frequently exhibit a cup-like shape without any constriction or pore. The cup-like caveolar shape could also be shown by tilt series analysis of freeze-fracture replicas obtained from cryofixed cells. Freeze-fracture immunolabeling of caveolin-1 revealed a lateral belt-like caveolin alignment. These findings point out that the constricted “neck” region of caveolae in most cases is an effect that is caused and intensified by the glutaraldehyde fixation. Our data indicate that caveolae in vivo show all degrees of invagination from nearly flat via cup-like depressed to in a few cases omega-like.