Vaccine potential of a recombinant glutathione S-transferase cloned from Schistosoma haematobium in primates experimentally infected with an homologous challenge

Patas monkeys were twice immunized with a Schistosoma haematobium-derived recombinant glutathione S-transferase (Sh28GST) then challenged with an homologous calibrated challenge. BCG and Freund's Complete Adjuvant (FCA) were used as adjuvants in two distinct protocols. Specific IgG and IgA antibody responses were intense and homogeneous in the animals receiving Sh28GST in the presence of FCA, whereas BCG could only induce moderate and heterogeneous antibody titres. No significant effect on worm burdens was evidenced 36 weeks post-infection in either group of Sh28GST-immunized animals compared to their matched controls receiving an irrelevant protein. Although not significant, 50% reductions in the numbers of eggs located in all tissues (FCA group) and in the urogenital system (BCG group) were noted. Moreover, the total number of excreted eggs was dramatically diminished by 60% and 77% in the BCG and FCA groups, respectively. These reductions reached 75% and 80% in the urines of vaccinated monkeys. Bladder pathology was also reduced in the animals displaying the lowest urinary egg excretions. There was no clear positive or negative correlate between antibody responses and individual levels of protection. Taken as a whole, our results show that Sh28GST was capable of significantly reducing S. haematobium worm fecundity in experimentally infected primates. Although FCA induced higher levels of protection, the efficacy of BCG as an adjuvant appeared sufficient to justify consideration of the future application of this new formulation as a vaccine against human urogenital schistosomosis.     

Malignant hyperthermia and neuroleptic malignant syndrome in a patient during treatment for acute asthma

PURPOSE: The safety and diagnostic efficacy of iodixanol (Visipaque) 270 mg I/ml was compared to that of iopamidol (Iopamiron) 300 mg I/ml in knee arthrography. MATERIAL AND METHODS: This trial was a bi-center double-blind trial including 128 patients (iodixanol/iopamidol 64/64 patients). Efficacy was evaluated by blinded grading of the diagnostic quality of the p.a. images taken 0, 12 and 25 min after contrast administration by the examining radiologist and later at a consensus evaluation by two experienced skeletal radiologists. Adverse events were recorded. RESULTS: No patient experienced any adverse event. The proportion of better images at both 12 and 25 min after injection was higher in the iodixanol group compared to the iopamidol group both by the examining radiologist and at the consensus evaluation. CONCLUSION: In the knee joint iodixanol is a safe contrast medium. The contrast effect of iodixanol lasted longer than that of iopamidol, which can be important when performing arthrography, especially CT arthrography, where the time between puncture and examination can be prolonged.     

Optimization of Dynamic Hardware Reconfigurations

Recent generations of Field Programmable Gate Arrays (FPGA) allow the dynamic reconfiguration of cells on the chip during run-time. For a given problem consisting of a set of tasks with computation requirements modeled by rectangles of cells, several optimization problems such as finding the array of minimal size to accomplish the tasks within a given time limit are considered. Existing approaches based on ILP formulations to solve these problems as multi-dimensional packing problems turn out not to be applicable for problem sizes of interest. Here, a breakthrough is achieved in solving these problems to optimality by using the new notion of packing classes. It allows a significant reduction of the search space such that problems of the above type may be solved exactly using a special branch-and-bound technique. We validate the usefulness of our method by providing computational results.     

Cortisol in physiological concentrations acts within minutes to modify effects of prolactin and growth hormone on prostaglandin secretion: importance of effect in modulating cellular responses to calcium and cyclic nucleotides

We propose that intracellular prostaglandins (PGs) are essential for the final expression of the effects of second messengers in most cells. We suggest that the amounts of PGs required are very small (in the picomolar range) and are much lower than those used in most current PG studies. We suggest that while therapeutic levels of inhibitors of PG synthetase may be adequate to block the overflow of PGs from cells, they are in most cases unlikely to reduce intracellular PGs sufficiently to test the role of such PGs. We propose that there is a basal level of PG synthesis unaffected by hormones but that above this level PG synthesis is regulated by the interplay between physiological levels of cortisol, prolactin, growth hormone and thyroid hormones. For the most part prolactin seems to stimulate PG synthesis and cortisol to inhibit it: cortisol has, however, no inhibitory effect on basal PG synthesis. In reducing prolactin-stimulated PG synthesis cortisol is 1000-2000 times more potent than indomethacin on a molar basis. We suggest that the regulation of intracellular PG levels is the mechanism of the so-called "permissive" actions of these hormones. These concepts could prove important in the understanding of many aspects of physiology and pathophysiology including diurnal and seasonal changes in hormone responsiveness. They are also relevant to the use of established drugs and the design of new ones.     

Occurrence of gastric ulcer after Nissen fundoplication

Of 160 patients who underwent Nissen fundoplication for treatment of symptomatic peptic reflux esophagitis, five patients (3.1%) developed gastric ulcers. Four of these five patients experienced the "gas-bloat" syndrome. All ulcers were located on the lesser curvature of the stomach. Analyses of our experience with use of various types of hiatal hernia repair suggests that creation of the valvuloplastic mechanism unique to the Nissen procedure may be of etiologic significance in the development of gastric ulcers following this procedure.     

Experimental electrocoagulation of dog esophageal and duodenal mucosa

The per review system for the assessment of research proposals is widely respected by working scientists. Nevertheless two problems associated with the operation of this system by the US National Institutes of Health are identified. First the scientist has no control over which committee will review an application and it may be considered by a quite inappropriate group. Second analysis of the committee composition suggests that in some of the groups several members are not active scientists and therefore not the "peers" of the applicant.     

Acceptability of three convenience chicken products

Three convenience products--frozen, precooked chicken apple fritters, chicken breast fillets, and chicken patties--provided by one processor were subjectively evaluated by two taste panels of older adults, ranging in age from the sixties to middle eighties. The panelists represented a middle-income group maintaining private homes and a low-income group living in public housing. Both panels rated each product above "good" (score=4) or "fair" (score=3) on four acceptability factors and the overall score. Although mean scores of the low-income taste panel on all factors were generally higher for all products, the only significant difference (P less than .01) pertained to the appearance factor. Both panels indicated willingness to buy all three products.     

Occlusion pressures in men rebreathing CO2 under methoxyflurane anesthesia

The effect of general anesthesia on control of breathing was studied by CO2 rebreathing and occlusion pressure measurements in six normal human subjects under methoxyflurane anesthesia. CO2 was found to increase the amplitude of the occlusion pressure wave without changing its shape, so that CO2 responses in terms of the occlusion pressure developed 100 ms after the onset of inspiration (Po/0.1) gave results equivalent to the responses in terms of Po/1.o or any other parameter of the pressure wave. Methoxyflurane depressed the ventilatory response to CO2 but not the occlusion pressure response, implying that the most important action of the anesthetic was to increase the effective elastance of the respiratory system rather than to depress the respiratory centers. The elastance was further increased by CO2, and this mechanical change had the effect of shifting the "apneic threshold" extrapolated from the ventilatory response curve to a lower PAco2. Frequency of breathing, inspiratory and expiratory times were not altered by CO2 in anesthetized subjects.     

Pore functioning of outer membrane protein PhoE of Escherichia coli: mutagenesis of the constriction loop L3

Each monomer of the trimeric outer membrane porin PhoE of Escherichia coli consists of a 16-stranded beta-barrel with short turns at the periplasmic side and large loops at the cell surface. One of these loops, L3, is folded inside the beta-barrel and forms a constriction within the channel. Therefore, it is assumed to play an important role in the permeability properties of this general diffusion pore. Several site-directed mutations were introduced in loop L3 to investigate its function. The loop L3 contains a short alpha-helix and, at the tip of the loop, a highly conserved PEFGG sequence. The alpha-helix was deleted and the two glycines in the PEFGG sequence were either replaced by alanines or deleted. A serine residue, supposed to play an indirect role in the anion selectivity of the pore, was removed. The mutant porins were analysed both in vitro and in vivo. The results suggest that flexibility of the third loop is important for solute passage and that this flexibility is determined by the two glycine residues in the PEFGG sequence. Furthermore, the alpha-helix is probably important for the folding of the protein. The supposed involvement of Ser115 (Ser121A in OmpF nomenclature) in anion selectivity was confirmed.