The dual phases of the response to neonatal exposure to a VH family-restricted staphylococcal B cell superantigen

In vitro studies of several naturally occurring proteins have characterized VH family-specific B lymphocyte binding and stimulatory properties that appear analogous to those of T cell superantigens. To examine the in vivo consequences of exposure to a putative B cell superantigen, we treated neonatal BALB/c mice with a form of staphylococcal protein A (MS) devoid of Fcgamma binding activity, which retains the clan VHIII Fab binding specificity. In naive adults, about 5% of peripheral B cells and >13% of splenic IgM-secreting cells display MS binding activity, in association with high IgM and low IgG circulating anti-MS Ab titers. Neonatal exposure to MS elicited two distinct temporal phases of immune responsiveness. The early phase, representing the first approximately 5 wk of life, was associated with MS-specific B cell and T cell tolerance. Microfluorometric assays revealed that exposure caused a dramatic MS-specific B cell clonal loss in bone marrow and spleen, but levels normalized by about 3 wk of life. The late phase (>6 wk of age) was associated with spontaneous priming for MS-specific T cell responses and production of MS-specific IgG1 Abs despite long term persistently depressed in vivo and in vitro MS-specific IgM responses. In vivo challenge during the late phase induced high frequencies of MS-specific IgG-secreting cells, indicating recruitment of highly focused Ab responses that were predominantly encoded by rearrangements of the S107 family, a member of the VHIII clan. These studies document the immunodominance of the VH-restricted Fab binding site on staphylococcal protein A and demonstrate the diverse effects of a B cell superantigen on the emerging peripheral B cell compartment.     

Biosynthesis of 2-aceto-2-hydroxy acids: acetolactate synthases and acetohydroxyacid synthases

Two groups of enzymes are classified as acetolactate synthase (EC 4. 1.3.18). This review deals chiefly with the FAD-dependent, biosynthetic enzymes which readily catalyze the formation of acetohydroxybutyrate from pyruvate and 2-oxobutyrate, as well as of acetolactate from two molecules of pyruvate (the ALS/AHAS group). These enzymes are generally susceptible to inhibition by one or more of the branched-chain amino acids which are ultimate products of the acetohydroxyacids, as well as by several classes of herbicides (sulfonylureas, imidazolinones and others). Some ALS/AHASs also catalyze the (non-physiological) oxidative decarboxylation of pyruvate, leading to peracetic acid; the possible relationship of this process to oxygen toxicity is considered. The bacterial ALS/AHAS which have been well characterized consist of catalytic subunits (around 60 kDa) and smaller regulatory subunits in an alpha2beta2 structure. In the case of Escherichia coli isozyme III, assembly and dissociation of the holoenzyme has been studied. The quaternary structure of the eukaryotic enzymes is less clear and in plants and yeast only catalytic polypeptides (homologous to those of bacteria) have been clearly identified. The presence of regulatory polypeptides in these organisms cannot be ruled out, however, and genes which encode putative ALS/AHAS regulatory subunits have been identified in some cases. A consensus sequence can be constructed from the 21 sequences which have been shown experimentally to represent ALS/AHAS catalytic polypeptides. Many other sequences fit this consensus, but some genes identified as putative 'acetolactate synthase genes' are almost certainly not ALS/AHAS. The solution of the crystal structures of several thiamin diphosphate (ThDP)-dependent enzymes which are homologous to ALS/AHAS, together with the availability of many amino acid sequences for the latter enzymes, has made it possible for two laboratories to propose similar, reasonable models for a dimer of catalytic subunits of an ALS/AHAS. A number of characteristics of these enzymes can now be better understood on the basis of such models: the nature of the herbicide binding site, the structural role of FAD and the binding of ThDP-Mg2+. The models are also guides for experimental testing of ideas concerning structure-function relationships in these enzymes, e.g. the nature of the substrate recognition site. Among the important remaining questions is how the enzyme suppresses alternative reactions of the intrinsically reactive hydroxyethylThDP enamine formed by the decarboxylation of the first substrate molecule and specifically promotes its condensation with 2-oxobutyrate or pyruvate.     

Animal, vegetable or cerebral: brains in agricultural production

Recent developments in brain research seem to have passed unnoticed in veterinary and agricultural circles. Yet they have transformed views on the subject and, Dr Cross argues, made study of the brain mandatory for future advance in animal health and production.     

A diagnostic formula for alcoholism

Clinical pathologies with unusually high morbidities in alcoholic populations were analyzed to determine their capacity to diagnose alcoholism. On the basis of five systemic variables it was possible to diagnose correctly nearly 75% of alcoholic and matched control subjects.