Local airways immune modifications induced by oral bacterial extracts in chronic bronchitis

Bacterial extracts can act as immune stimulants and in some instances have been used, rather empirically, to prevent recurrent infections in the nonimmunocompromised host. Some agents are administered via oral route with the goal to increase airways immune defenses. In animal models and in normal humans, gut-associated lymphoid tissue (GALT) stimulation is able to induce a generalized response by the whole mucosal-associated lymphoid tissue (MALT). The aim of this placebo-controlled, double-blind, parallel-group study was to evaluate whether the stimulation of the GALT through oral administration of a polyvalent bacterial extract (BE) could lead to significant immune modifications either systemically or locally in the respiratory tract in patients suffering from chronic bronchitis. We selected 20 subjects (5 nonsmokers, 6 smokers, and 9 ex-smokers) for at least 3 years. According to a balanced-block randomization method, ten patients received active treatment and ten received placebo. Either drug or placebo was to be taken as one capsule daily the first 10 days of 3 consecutive months. Each capsule of the active product contained 7 mg of a BE obtained from eight different bacterial strains. On entry (T0) and 90 days after beginning of treatment (T90), all patients underwent bronchoalveolar lavage (BAL) and peripheral blood withdrawal to assay BAL fluids and serum samples for immune parameters. The BAL recoveries, cellularity, cell differentials, and lymphocyte subsets (CD19, CD3, CD4, CD8) did not show significant differences. IgG/albumin and IgA/albumin values were not significantly different, but IgA/albumin was significantly increased in the treatment (T0 = 0.14, 0.01 to 0.27, median and range, T90 = 0.15, 0.08 to 0.45, p = 0.028) vs the placebo group when data from current smokers were excluded. Functional tests on alveolar macrophages (AM) (leading front stimulated motility and superoxide anion-O2(-)-release) showed a significant increase of random migration (T0 = 10.6, 7.0 to 23.6, T90 = 13.4, 8.1 to 28.8 microns, p = 0.02) and of stimulated motility after FMLP 10(-7) M (T0 = 13.2, 8.3 to 46.4, T90 = 18.3, 8.4 to 49.6 microns, p = 0.04), a significant increase of O2- release in basal conditions (T0 = 6.0, 1.7 to 30.5 nM/10(6) AM/10', T90 = 11.1, 5.5 to 24.5, p = 0.05) and after stimulation with opsonized zymosan (T0 = 17.7, 4.7 to 35.2, T90 = 22.1, 13.8 to 53.3, p = 0.009) in the treatment group only. Data were not significantly different in the placebo group between T0 and T90. No modifications in systemic immunity were ever observed.(ABSTRACT TRUNCATED AT 400 WORDS)     

Double-strand break repair in the absence of RAD51 in yeast: a possible role for break-induced DNA replication

In wild-type diploid cells of Saccharomyces cerevisiae, an HO endonuclease-induced double-strand break (DSB) at the MAT locus can be efficiently repaired by gene conversion using the homologous chromosome sequences. Repair of the broken chromosome was nearly eliminated in rad52delta diploids; 99% lost the broken chromosome. However, in rad51delta diploids, the broken chromosomes were repaired approximately 35% of the time. None of these repair events were simple gene conversions or gene conversions with an associated crossover, instead, they created diploids homozygous for the MAT locus and all markers in the 100-kb region distal to the site of the DSB. In rad51delta diploids, the broken chromosome can apparently be inherited for several generations, as many of these repair events are found as sectored colonies, with one part being repaired and the other part being lost the broken chromosome. Similar events occur in about 2% of wild-type cells. We propose that a broken chromosome end can invade a homologous template in the absence of RAD51 and initiate DNA replication that may extend to the telomere, 100 or more kb away. Such break-induced replication appears to be similar to recombination-initiated replication in bacteria.     

Hydrocyanic acid levels in fermented cassava

The extent of loss of hydrocyanic acid during the fermentation of cassava tubers selected from both sweet and bitter varieties in the traditional method (whole unpeeled tubers) compared with the fermentation of peeled tubers and crushed pulps with or without the addition of water. Although the traditional fermentation is terminated after 3–4 days, in this study the fermentation was allowed to proceed for 8 days. Loss of cyanide from the whole tubers was 8047% after 8 days and was only 51–53% after 4 days. Loss of cyanide from the whole sweet tuber was not significant after 5 days. The loss of cyanide from the peeled tubers was comparable to the whole tubers after 8 days of fermentation. However, there was a marked decrease in free cyanide in the 1st day of fermentation of the peeled tubers compared to whole tubers. The loss in cyanide in the crushed pulp, which occurred primarily in the 1st day, appears to be due to the action of endogenous linamarase rather than hydrolysis by fermentation. When water is added to the crushed pulp the reduction in cyanide was 83–91% with marked decrease in bound cyanide in the 1st day of fermentation. It seems that autohydrolysis is enhanced by addition of water to the crushed pulp.     

Neurologic disease in Sj?gren's syndrome: mononuclear inflammatory vasculopathy affecting central/peripheral nervous system and muscle. A clinical review and update of immunopathogenesis

There is a growing appreciation that a subset of patients with primary Sj?gren's syndrome (SS) also may develop a spectrum of central nervous system (CNS) complications. This article defines SS and its significance; discusses CNS, peripheral nervous system, and muscular complications of SS; identifies those areas in general or internal medicine in which SS patients with potential neurologic complications may present; describes those neurologic disorders that SS may mimic; places into perspective the controversy regarding the frequency and significance of CNS-SS; and extends our observations on the immunopathogenesis of neurologic complications in SS.