Lisofylline prevents leak, but not neutrophil accumulation, in lungs of rats given IL-1 intratracheally

Hybertson, Brooks M., Stuart L. Bursten, Jonathan A. Leff,Young M. Lee, Eric K. Jepson, Chris R. Dewitt, John Zagorski, Hyun G. Cho, and John E. Repine. Lisofylline prevents leak, but not neutrophil accumulation, in lungs of rats given IL-1intratracheally. J. Appl. Physiol.82(1): 226-232, 1997.Interleukin-1 (IL-1) is increased in lunglavages from patients with the acute respiratory distress syndrome, andadministering IL-1 intratracheally causes neutrophil accumulation and aneutrophil-dependent oxidative leak in lungs of rats. In the presentstudy, we found that rats pretreated intraperitoneally with lisofylline[(R)-1-(5-hydroxyhexyl)-3,7-dimethylxanthine (LSF)], an inhibitor of lysophosphatidic acid acyl transferase, which reduces the production of unsaturated phosphatidic acid species,did not develop the lung leak or the related ultrastructural abnormalities that occur after intratracheal administration of IL-1.However, rats pretreated with LSF and then given IL-1 intratracheally did develop the same elevations of lung lavage cytokine-induced neutrophil chemoattractant (CINC) levels and the same increased numbersof lung lavage neutrophils as rats given IL-1 intratracheally. Lungs ofrats given IL-1 intratracheally also had increased unsaturated phosphatidic acid and free acyl (linoleate, linolenate) concentrations compared with untreated rats, and these lipid responses were prevented by pretreatment with LSF. Our results reveal that LSF decreases lungleak and lung lipid alterations without decreasing neutrophil accumulation or lung lavage CINC increases in rats given IL-1 intratracheally.

     

Catalytic components of proteasomes and the regulation of proteinase activity

The proteasome (multicatalytic proteinase complex) is a large multimeric complex which is found in the nucleus and cytoplasm of eukaryotic cells. It plays a major role in both ubiquitin-dependent and ubiquitin-independent nonlysosomal pathways of protein degradation. Proteasome subunits are encoded by members of the same gene family and can be divided into two groups based on their similarity to the and subunits of the simpler proteasome isolated fromThermoplasma acidophilum. Proteasomes have a cylindrical structure composed of four rings of seven subunits. The 26S form of the proteasome, which is responsible for ubiquitin-dependent proteolysis, contains additional regulatory complexes. Eukaryotic proteasomes have multiple catalytic activities which are catalysed at distinct sites. Since proteasomes are unrelated to other known proteases, there are no clues as to which are the catalytic components from sequence alignments. It has been assumed from studies with yeast mutants that -type subunits play a catalytic role. Using a radiolabelled peptidyl chloromethane inhibitor of rat liver proteasomes we have directly identified RC7 as a catalytic component. Interestingly, mutants in Prel, the yeast homologue of RC7, have already been reported to have defective chymotrypsin-like activity. These results taken together confirm a direct catalytic role for these -type subunits. Proteasome activities are sensitive to conformational changes and there are several ways in which proteasome function may be modulatedin vivo. Our recent studies have shown that in animal cells at least two proteasome subunits can undergo phosphorylation, the level of which is likely to be important for determining proteasome localization, activity or ability to form larger complexes. In addition, we have isolated two isoforms of the 26S proteinase.     

Long–term responses to factorial, NPK fertilizer treatment by Alaskan wet and moist tundra sedge species

At thirteen sites in northern and central Alaska, full factonal and partial factonal NPK fertilizer experiments were completed in wet and moist tundras The effects of the fertilizers on N and P concentrations in leaves, leaf mass per tiller, tilling, and flowering of the dominant sedge species ( Eriophorum vaginatum. E angustifolium, and Carex aquatilis ) were documented for 3–10 yr at each site Almost all sites showed at least some response to the fertilizer treatment, but the specific treatments and elements that caused the responses varied greatly among sites There also was no consistent difference in responses between wet and moist sites There was, however, a consistent temporal pattern to the responses observed, starting with increases in N and P concentration in leaves in the year that fertilizer was added, followed by growth and tilling responses in the second year, and increased flowering in the third year The increases in N concentration generally only appeared in the first year, while increased P concentrations were sustained for 3–4 yr Effects of fertilizer on flowering were still significant after 6 years in some cases Results are discussed in terms of the role of "nutrient limitation" arctic plant communities and detemuning their productivity following disturbance or fertilization     

Febrile Gastroenteritis Due to Salmonella thompson—Report of an Outbreak

Salmonella thompson, a common pathogen of poultry, has received scant attention as a cause of human gastroenteritis. At least 45 persons were infected with S thompson in Sacramento, California, after eating at a chicken restaurant and 38 became symptomatic. Ten required admission to hospital, and all were treated with antibiotics and improved. In 19 cases cultures of stool specimens for S thompson over a 60-day period showed slower but statistically insignificant differences in salmonellal elimination in 7 patients who received antibiotics when compared with 12 who were untreated. We report this outbreak to increase awareness of the virulence and prevalence of gastroenteritis due to S thompson.     

Inhibited light activation of fructose and sedoheptulose bisphosphatase in spinach chloroplasts exposed to osmotic stress

The light activation of fructose-1,6-bisphosphatase (EC 3.1.3.11) and sedoheptulose-1,7-bisphosphatase (EC 3.1.3.37) was inhibited in isolated intact spinach (Spinacia oleracea L.) chloroplasts exposed to reduced osmotic potentials. Decreases in the velocity and magnitude of light activation correlated with the overall reduction in CO₂ fixation rates. Responses of osmotically stressed chloroplasts to both varying pH and exogeous dihydroxyacetone phosphate (DHAP) or 3-phosphoglycerete (PGA) were examined. In the presence of DHAP, the absolute rate of CO₂ fixation was increased and this increase was most pronounced at alkaline pH. Enhanced light activation of these enzymes was also observed under these conditions. However, in the presence of PGA, similar increases in photosynthetic rate and enzyme activation were not evident. Light-dependent stromal alkalization was unaffected by the stress treatments. Inhibition of light activation under hypertonic conditions is discussed in terms of substrate availability, possible alterations of the redox state of ferredoxin and associated electron carriers, and inhibited enzyme-enzyme or enzyme-substrate interactions involved in the light activation process.Abbreviations and symbols DHAP dihydroxyacetone phosphate - PGA 3-phosphoglycerate - _s osmotic potential     

Golgi-mediated vicilin accumulation in pea cotyledon cells is re-directed by monensin and nigericin

Summary A range of drugs was applied to developing pea seed cotyledons in an attempt to perturb the intracellular transport of newly synthesized vicilin through the endoplasmic reticulum and Golgi vesicles to its site of storage, the vacuole. The most pronounced effects, produced by the ionophores monensin and nigericin, were on Golgi-mediated transport. Unlike the situation in most other tissues that have been studied the number of Golgi vesicles did not increase, suggesting that their movement is not slowed or stopped. However, the Golgi-mediated transport of vicilin was redirected from the vacuole tonoplast to the plasmalemma and the newly synthesized vicilin was released from the cotyledon cells to accumulate between the plasmalemma and the cell wall.     

Characterization of a new marine methylotroph

Abstract A methanol-oxidizing bacterium from a marine environment has been isolated and characterized. The bacterium was a Gram-negative rod, capable of growth on methanol and methylamine, but not on multicarbon compounds. It showed a temperature optimum of 30°C, a salt optimum of 0.4% (w/v) and the mol % G + C of its DNA was 46%. Carbon was assimilated via the ribulose monophosphate pathway for formaldehyde fixation during growth on methanol. This bacterium superficially resembled other obligate methylotrophs requiring NaCl reported previously which were designated Methylomonas thalassica . It also appeared similar to many strains of obligate freshwater methylotrophs, except for its NaCl requirement and its lower mol % G + C.     

Pigmentation and autofluorescence of Cryptococcus species after growth on tryptophan and anthranilic acid media

Cryptococcus neoformans and Candida albicans produced a pink pigment from media containing tryptophan. Approximately 30% of the C. neoformans strains produced large amounts of the pink (purple after 6 days) pigment in the absence of light whereas 70% of the Cryptococcus neoformans strains, as well as C. laurentii, C. albidus, C. diffluens, and C. albicans also produced the pink pigment with light being required for significant early production (2–6 days). Significant production did occur for Cryptococcus but not Candida species in the dark after extended incubation (10–25 days). C. terreus produced brown pigments from tryptophan and C. luteolus produced a trace of a buff pigment. Most Candida species produced either pink or brown pigments but not both. In contrast, many Cryptococcus species producing the pink pigment simultaneously produced brown pigments. C. terreus, C. albidus, and C. diffluens produced brown pigments from anthranilic acid whereas C. neoformans, C. laurentii, C. luteolus, and the medically important Candida species did not produce significant amounts of pigments from anthranilic acid. Cryptococcus and Candida species were autofluorescent when tryptophan was a major nitrogen source whereas yeast cell autofluorescence was not observed when anthranilic acid was used. Pigmentation of some Cryptococcus species also the substrate.Operated for the U.S. Department of Energy under contract number EY-76-C-05-0033This article is based on work supported by the Division of Biomedical and Environmental Research.     

Haemophilia A home therapy in the United Kingdom 1975-6.

Data on home treatment for patients with haemophilia A (factor VIII deficient haemophilia) were compiled for 1975 and 1976 from questionnaires answered by directors of haemophilia centres throughout the United Kingdom. There were 48 haemophilia centres in 1975 and 71 in 1976. The number of patients on or in training for home treatment increased from 267 to 488 in the two years, and a further 241 haemophiliacs were considered suitable for home therapy by the end of 1976. Apart from a small (but increasing) number of haemophiliacs on prophylactic treatment, most patients were on low-dose (250-500 units) on-demand regimens, using a mean of 20 000 factor VIII units per patient per year in 1976. An estimated 55% of the blood product used for home therapy in the UK in 1976 was imported from commercial sources. Despite the fact that the numbers of patients on home treatment have increased, so that about 60% of the potential population were receiving or being considered for home treatment in 1976, inadequacies in the service still remain. In some centres follow-up is clearly inadequate; about 15% of patients still rely on cryoprecipitate; and too little money has been invested in making the NHS self-sufficient in factor VIII production.