Biochem J, 1986 Nov 1, 239(3), 733 - 8 Isolation and identification of uridine(5')-diphospho(1)-2,3-diacetamido-2,3-dideoxy-alpha-D- glucopyra nuronic acid from Pseudomonas aeruginosa P1-III; Okuda S et al.; A new uridine nucleotide was isolated from Pseudomonas aeruginosa P1-III (Habs serotype 5) . On the basis of 13C-n.m.r . and p.m.r . spectroscopy, mass spectrometry, i.r.-absorption spectroscopy and circular dichrometry, the structure of the new compound was unequivocally identified as uridine(5')-diphospho(1)-2,3-diacetamido-2,3-dideoxy-alpha-D-gl ucopyranuronic acid. Mol Gen Mikrobiol Virusol, 1986 Nov, (11), 18 - 23 {Genetic characteristics and physical organization of the R-plasmid pBS52 with a broad range of bacterial hosts}; Polevoda BV et al.; The genetic and physical data on Pseudomonas aeruginosa plasmid pBS52 coding for the resistances to ampicillin, streptomycin and sulfonamids have been obtained . This conjugative plasmid is transferable to a broad range of gram-negative bacterial hosts and compatible with the broad host-range plasmids from all known incompatibility groups . The plasmid size has been determined (38 Kb) and a physical map has been constructed using restriction endonucleases EcoRI, EcoRV, BamHI, BglII, PstI, PvuII, SalI, SlaI . The presence of a fragment, approximately 200 bp in size, which contains the sites for many of widely used restriction endonucleases is a characteristic feature of the plasmid pBS52. Mol Biol (Mosk), 1986 Nov-Dec, 20(6), 1589 - 92 {Effect of ligand orientation on the redox potential of homologous proteins}; Denisenko AN; Using experimental g-values of homologous cytochromes isolated from the horse heart and bacterial cyt-c-551 from Pseudomonas aeruginosa, the electron energy difference of redox-orbital of Fe(III) ion of heme was calculated during reduction . Data are in a good accordance with experimental redox-potential values for these proteins . The model gives opportunity to predict redox-potential values for other homologous proteins. Genetika, 1986 Nov, 22(11), 2721 - 7 {Cloning and characteristics of recA gene in Pseudomonas aeruginosa}; Zaitsev EN et al.; A recA-like gene from Pseudomonas aeruginosa was cloned and identified by means of interspecific complementation of gene recA repair defect in Escherichia coli . The gene was mapped in the PvuII-HindIII Ps . aeruginosa chromosome fragment of 1.5 kbp in length . Having been recloned in pUC18 or 19 plasmids in either of possible orientations, this fragment was shown to complement three different defects of E . coli recA mutants: in repair, recombination and SOS functions. Genetika, 1986 Nov, 22(11), 2637 - 48 {2 types of molecular structure (composition) of a genome in one species of transposable bacteriophages of Pseudomonas aeruginosa}; Krylov VN et al.; Comparison of heteroduplexes (HD) between DNAs of different transposable phages of Pseudomonas aeruginosa belonging to two previously described subgroups (D3112 and B3) revealed two types of structure (composition) of the bacteriophages, designated "type A" and "type B" . The properties of genome structure of type A (phages of D3112 subgroup) are as follows: high level of conservation (up to 70% of genomes of different phages are represented as blocks of homologous DNA sequences); substitutions in genomes revealed as nonhomology regions in HD are, as a rule, small and located in certain sites; the distribution of the nonhomologous regions in HD of these phages is highly reproducible in independent experiments . Bacteriophages of subgroup B3 have genomes of type B: only a small part (approx . 30%) of genomes retain homology general for all of the phages; the nonhomologous regions are distributed in a large number of sites in HD; the sizes of nonhomologous regions are substantially larger than for the phages of subgroup D3112; distribution of the regions in HD is highly variable, which is characteristic of DNAs with partial homology . There is no difference between genomes of types A and B in G + C content (approx . 61-63%) . Viable recombinants can be formed in crosses between phages of different genome types not only in regions with earlier revealed large DNA/DNA homology (right ends of genomes), but also in central portions of the genomes . Nevertheless, functional incompatibility of some regions of phage genomes of types A and B was demonstrated. Antimicrob Agents Chemother, 1986 Nov, 30(5), 802 - 5 Distribution of porin and lipopolysaccharide antigens on a Pseudomonas aeruginosa permeability mutant; Godfrey AJ et al.; Pseudomonas aeruginosa common surface antigens were compared in a permeability mutant (PCC118) and its parent (PAO503) . The distribution of lipopolysaccharide and porin antigens in the mutant supports the conclusion that beta-lactam permeability was affected by lipopolysaccharide-side chain presentation rather than by a change in porin number. J Trauma, 1986 Nov, 26(11), 1013 - 23 Factor XIII as a modulator of plasma fibronectin alterations during experimental bacteremia; Kiener JL et al.; Fibronectin is found in plasma as well as in association with connective tissue and cell surfaces . Depletion of plasma fibronectin is often observed in septic trauma and burned patients, while experimental rats often manifest hyperfibronectinemia with sepsis . Since Factor XIII may influence the rate of clearance and deposition of plasma fibronectin into tissues, we evaluated the temporal changes in plasma fibronectin and plasma Factor XIII following bacteremia and RE blockade in rats in an attempt to understand the mechanism leading to elevation of fibronectin levels in bacteremic rats, which is distinct from that observed with RE blockade . Clearance of exogenously administered fibronectin after bacteremia was also determined . Rats received either saline, Pseudomonas aeruginosa (1 X 10(9) organisms), gelatinized RE test lipid emulsion (50 mg/100 gm B.W.), or emulsion followed by Pseudomonas . Plasma fibronectin and Factor XIII were determined at 0, 2, 24, and 48 hours post-blockade or bacteremia . At 24 and 48 hr following bacteremia alone or bacteremia after RE blockade, there was a significant elevation (p less than 0.05) of plasma fibronectin and a concomitant decrease (p less than 0.05) of plasma factor XIII activity . Extractable tissue fibronectin from liver and spleen was also increased at 24 and 48 hours following R.E . blockade plus bacteremia . In addition, the plasma clearance of human fibronectin was significantly prolonged (p less than 0.05) following bacterial challenge . Infusion of activated Factor XIII (20 units/rat) during a period of hyperfibronectinemia (908.0 +/- 55.1 micrograms/ml) resulted in a significant (p less than 0.05) decrease in plasma fibronectin (548.5 +/- 49.9 micrograms/ml) within 30 min . Thus Factor XIII deficiency in rats with bacteremia may contribute to the elevation in plasma fibronectin by altering kinetics associated with the clearance of fibronectin from the blood. J Bacteriol, 1986 Nov, 168(2), 574 - 80 Expression of pili from Bacteroides nodosus in Pseudomonas aeruginosa; Elleman TC et al.; The pili of Bacteroides nodosus, the causative agent of ovine footrot, constitute the major host-protective immunogen against homologous serotypic challenge . The pilin gene from B . nodosus 198 has been cloned and morphologically expressed as extracellular pili in Pseudomonas aeruginosa by using a plasmid-borne, thermoregulated expression system . B . nodosus pilin could not be detected in cultures of P . aeruginosa grown at 32 degrees C, but after induction at 37 degrees C, B . nodosus pili were expressed on the cell surface of P . aeruginosa to the virtual exclusion of the host cell pili . Pili harvested from induced P . aeruginosa cultures were used to immunize sheep against footrot . The serum agglutinating antibody titers of vaccinated sheep were comparable to those of sheep receiving pili from B . nodosus . Subsequent challenge of the sheep with B . nodosus 198 indicated that the recombinant- DNA-derived pili vaccine and the B . nodosus pili vaccine provided similar levels of protection against footrot. Arzneimittelforschung, 1986 Oct, 36(10), 1511 - 7 Antibacterial activity and ototoxicity in guinea pigs, and nephrotoxicity in rats of arbekacin; Kurebe M et al.; Arbekacin (HBK), 1-N{(S)-4-amino-2-hydroxybutyl}-3',4'-dideoxykanamycin B, showed broad antibacterial spectra against gram-positive and gram-negative bacteria including Pseudomonas aeruginosa . It was also effective against gentamycin- or tobramycin-resistant bacteria . HBK was resistant to various aminoglycoside-inactivating enzymes except for AAC (2') and AAC (6')-IV, both of which slowly inactivated it . Even at higher dosages (150 mg/kg i.m . or greater, which resulted in some deaths), HBK never decreased the pinna reflex in guinea pigs, while 150 mg/kg or more of dibekacin (DKB) or amikacin (AMK) caused loss of this reflex . HBK has less ototoxicity than do DKB and AMK . This was confirmed by histopathological examination of the inner ear . The degree of nephrotoxicity of HBK was suggested to be similar to that of DKB as judged from serum biochemical tests, urinalysis, and histopathological findings. Biochem J, 1986 Oct 1, 239(1), 221 - 4 The determination of specificity constants in enzyme-catalysed reactions; Crompton IE et al.; A convenient and accurate procedure for determining the kinetic parameter Vmax./Km is described . This avoids the error in the usual method of taking the observed first-order rate constant of an enzymic reaction at low substrate concentration as Vmax./Km . A series of reactions is used in which the initial concentration of substrate is below Km (e.g . from 5% to 50% of Km) . Measurements are taken over the same extent of reaction (e.g . 70%) for each member of the series, and treated as if the kinetics were truly first-order . The reciprocal of the observed first-order rate constant is then plotted against the initial concentration of substrate: the reciprocal of the ordinate intercept is Vmax./Km . The procedure, as well as being applicable to simple reactions, is shown to be valid when there is competitive inhibition by the product, or when the reaction is reversible, or when there is competitive or mixed inhibition . The hydrolysis of cephalosporin C by a beta-lactamase from Pseudomonas aeruginosa is used to illustrate the method. Antimicrob Agents Chemother, 1986 Oct, 30(4), 614 - 6 Pharmacokinetics and sputum penetration of ciprofloxacin in patients with cystic fibrosis; Smith MJ et al.; Levels of ciprofloxacin in serum and sputum were studied for eight patients with cystic fibrosis who were infected with Pseudomonas aeruginosa . Patients were studied in a steady state on a dosage of 500 mg every 8 h . Peak levels in serum ranged from 1.27 to 5.6 mg/liter (mean, 3.16 +/- 1.27), and absorption was rapid, the time to peak concentration ranging from 0.5 to 3.0 h (mean, 1.5 +/- 0.9) . The antibiotic penetrated sputum well, achieving areas under the curve of approximately 46% of those obtained in serum. Scand J Clin Lab Invest, 1986 Oct, 46(6), 511 - 8 Increased mole fraction of arachidonic acid in bronchial phospholipids in patients with cystic fibrosis; Gilljam H et al.; The fatty acid pattern of the phospholipids in the bronchial secretion of patients with cystic fibrosis (CF) showed an increase of the mole fraction of arachidonic acid (AA) in most phospholipid classes compared to normals . Increase of AA in some classes was also found in patients with chronic bronchitis and in patients chronically colonized with Pseudomonas aeruginosa but in the diphosphatidylglycerol, lysophosphatidylethanolamine and sphingomyelin phospholipids, high fractions of AA was found exclusively in CF patients . Arachidonic acid was found to attain the highest ratios in CF in seven of the nine major bronchial phospholipids compared to the controls . There was no difference in the ratio saturated/unsaturated fatty acids between the CF patients and the control groups . A tendency towards unsaturation of the fatty acids in the bronchial secretion seems to be characteristic of infection and inflammation but AA appears to be more markedly increased in CF . Thus, the recorded changes may be characteristic for CF and not secondary to infection and/or inflammation in general, nor to P . aeruginosa colonization. Exp Mol Pathol, 1986 Oct, 45(2), 193 - 206 Morphologic and microbiologic features of Pseudomonas aeruginosa pneumonia in normal hamsters; Coalson JJ et al.; A model of pneumonia due to Pseudomonas aeruginosa was produced in hamsters by an intratracheal bolus instillation of microorganisms . Sequential lung changes from 4 hr through 11 days were studied by morphologic and microbiologic methods . Hamsters inoculated with greater than 10(6) pseudomonads survived but consistently had histologic evidence of mild bronchopneumonia 24 hr postinoculation, whereas a severe bronchopneumonia and a 100% mortality were elicited with a 10(8) inoculum of organisms in 0.5 ml phosphate-buffered saline (PBS) . An inoculum of 10(7) pseudomonads/0.5 ml PBS was then used to define the changes in the bacterial population in Pseudomonas pneumonia and to obtain serial histopathologic observations . Quantitative lung cultures obtained within 1 hr postinoculation demonstrated a mean of 10(6) colony forming units per lung, and none of the hamsters were bacteremic . However, by 24 hr bacterial counts had increased and all animals were bacteremic . Bacterial proliferation continued through 48 hr; however, the number of bacteremic animals had decreased . By 72 hr, bacterial counts had decreased with total Pseudomonas clearance noted by 120 hr . A striking polymorphonuclear leukocyte-rich alveolar exudate was present by 12 hr . Pseudomonas "vasculitis" was evident by 24 hr . The evolution of this vascular lesion correlated with the bacteremic state of the hamsters . By 11 days, resolution of the pneumonic process was seen . The macroscopic and microscopic features of this hamster model of Pseudomonas pneumonia are very similar to those reported in infected patients. Drug Intell Clin Pharm, 1986 Oct, 20(10), 767 - 9 Therapy of choice for the empiric treatment of the febrile neutropenic patient; Barriere SL; Patients who become neutropenic secondary to chemotherapy for malignancy are at high risk for bacterial infection . Since the most common organisms include enteric gram-negative bacilli and staphylococci, drug combinations have traditionally been used . In addition, available clinical evidence suggests that synergistic drug combinations are most effective in the treatment of infections due to Pseudomonas aeruginosa . Comparative clinical trials have not shown any particular drug combination to be superior to others tested . Therefore, the drug choice for the combination should be based on local susceptibility patterns, clinical experience, and cost . Newer beta-lactam compounds are broader in spectrum and more potent than older drugs, and have been tested as sole agents in this setting . Although results appear promising for drugs such as cefoperazone or ceftazidime, the development of resistance and lack of adequate antistaphylococcal activity preclude routine use of these drugs . Imipenem is currently undergoing clinical trials for this purpose and appears to have the appropriate breadth of spectrum . However, frequent development of resistance among isolates of P . aeruginosa is problematic . At the present time a combination of an aminoglycoside and an extended-spectrum penicillin seems to be the therapy of choice for the febrile, neutropenic patient. Surgery, 1986 Oct, 100(4), 679 - 90 A critical comparison of the hematologic, cardiovascular, and pulmonary response to steroids and nonsteroidal anti-inflammatory drugs in a model of sepsis and adult respiratory distress syndrome; Kopolovic R et al.; Improved survival of patients receiving high-dose steroid therapy in sepsis and adult respiratory distress syndrome (ARDS) has been reported, but such therapy and its benefits remain controversial . Recently research has been directed toward manipulation of the arachidonic acid cascade . Improved survival and hemodynamics with administration of nonsteroidal anti-inflammatory drugs (NSAID) have been reported in animal models of sepsis and ARDS . The purpose of this study was to compare the effects of steroids (methylprednisolone) and NSAID (ibuprofen) in a porcine model of septic ARDS induced by a continuous infusion of live Pseudomonas aeruginosa . Cardiopulmonary parameters were monitored in animals intubated, paralyzed, and ventilated at a 250 ml tidal volume and 0.5 Fio2 . Pigs were randomly assigned to one of five groups: groups I and II received respective doses of 12.5 mg/kg ibuprofen and 30 mg/kg methylprednisolone at 20 and 210 minutes after baseline; group III had P . aeruginosa only; groups IV and V received respective doses of ibuprofen and methylprednisolone at 20 and 210 minutes of sepsis . Significant pulmonary edema, increased intrapulmonary shunting, hypoxemia, hemoconcentration, and systemic hypotension occurred with P . aeruginosa infusion . In septic animals treated with ibuprofen normal systemic arterial pressure was maintained, hemoconcentration was decreased, and oxygenation was improved with a significant decrease in shunting and pulmonary edema . Administration of methylprednisolone improved hemoconcentration and cardiac index, but no significant effect on pulmonary edema, intrapulmonary shunting, or oxygenation was observed . The results of this study demonstrated a significant beneficial effect of ibuprofen and we would encourage controlled clinical trials of this drug in the management of sepsis and ARDS . On the other hand, methylprednisolone was found to be relatively ineffective in treatment of circulatory collapse and ARDS associated with sepsis. Invest Ophthalmol Vis Sci, 1986 Oct, 27(10), 1466 - 9 The role of the polymorphonuclear leukocyte in the induction of corneal edema; Chusid MJ et al.; Corneal inflammation is frequently associated with the development of corneal edema . It has been suggested the development of corneal edema might in some way be related to the presence of polymorphonuclear leukocytes (PMNLs) within inflamed corneas . In the present studies, it was found that corneal thickness markedly increased after experimental infection with Pseudomonas aeruginosa, but in guinea pigs made neutropenic by whole body irradiation, significantly less of an increase in corneal thickness occurred . Furthermore, corneas from non-neutropenic animals experimentally infected with P . aeruginosa consistently showed a greater increase in water content than did infected corneas from neutropenic animals . Over the first 48 hr of infection, the increase in corneal water was directly proportional to the corneal ingress of radiolabelled PMNLs . Corneal inflammation induced by intracorneal injection of the PMNL chemotactic agents phorbol myristate acetate (PMA) or endotoxin was also associated with a significant increase in corneal water compared with neutropenic animals . These data strongly suggest that activated PMNLs in the cornea are responsible for the induction of corneal edema in infected corneas. Antimicrob Agents Chemother, 1986 Oct, 30(4), 528 - 31 Efficacy of ciprofloxacin in experimental aortic valve endocarditis caused by a multiply beta-lactam-resistant variant of Pseudomonas aeruginosa stably derepressed for beta-lactamase production; Bayer AS et al.; The emergence of multi-beta-lactam resistance is a limiting factor in treating invasive Pseudomonas infections with newer cephalosporins . The in vivo efficacy of ciprofloxacin, a new carboxy-quinolone, was evaluated in experimental aortic valve endocarditis caused by a strain of Pseudomonas aeruginosa which is stably derepressed for beta-lactamase production and is resistant to ceftazidime and multiple other beta-lactam agents . A total of 51 catheterized rabbits with aortic catheters in place were infected with this strain and then received no therapy (controls), ceftazidime (75 mg/kg per day), or ciprofloxacin (80 mg/kg per day) . Ciprofloxacin sterilized all blood cultures and significantly lowered vegetation densities of P . aeruginosa by day 2 of treatment versus controls (P less than 0.0005) and animals receiving ceftazidime (P less than 0.0005) . This beneficial effect of ciprofloxacin was also noted on therapy days 6 and 11 . Ciprofloxacin rendered most vegetations (85%) culture negative over the 11-day treatment period and achieved bacteriologic cure in 73% of animals (P less than 0.0005 versus other therapy groups) . Ciprofloxacin prevented bacteriologic relapse at 6 days posttherapy . No ciprofloxacin resistance was detected among Pseudomonas isolates from cardiac vegetations . Ciprofloxacin warrants further evaluation in vivo versus multi-drug-resistant gram-negative bacillary infections. Microbiol Sci, 1986 Oct, 3(10), 302 - 8 Pseudomonas aeruginosa and cystic fibrosis: unusual bacterial adaptation and pathogenesis; Govan JR et al.; Pseudomonas aeruginosa is an adaptable, saprophytic bacterium with the potential to cause a variety of opportunistic infections in compromised hosts . In patients with cystic fibrosis, chronic pulmonary colonization with mucoid alginate-producing mutants of P . aeruginosa is a major cause of morbidity and mortality and is an interesting example of microbial adaptation and host-bacterium interaction. Acta Pathol Microbiol Immunol Scand {C}, 1986 Oct, 94(5), 175 - 9 Effect of Pseudomonas aeruginosa proteases on human leukocyte phagocytosis and bactericidal activity; Kharazmi A et al.; The effect of Pseudomonas aeruginosa alkaline protease (AP) and elastase (Ela) on neutrophil phagocytosis and bactericidal activity was examined . It was found that both proteases reduced the phagocytic activity of the leukocytes against P . aeruginosa, whereas they had little effect on the phagocytosis of S . aureus . AP and Ela at concentration of up to 250 micrograms per ml (much higher than the levels detectable under in vivo conditions) did not interfere with the bactericidal activity of the leukocytes against both test organisms . Inhibition of phagocytosis by AP and Ela without effect on the bactericidal activity suggests that the P . aeruginosa proteases most probably exert their effect on the cell surface perhaps by proteolytic cleavage of the cell receptors which are necessary for phagocytosis. Zentralbl Bakteriol Mikrobiol Hyg {B}, 1986 Oct, 182(5-6), 551 - 7 {Decontamination of drinking water taps colonized with Pseudomonas aeruginosa}; Schoenen D et al.; Water taps in hospitals are quite often contaminated with Pseudomonas aeruginosa . It is possible that Pseudomonas aeruginosa is disseminated with the water . It seems necessary to disinfect the water taps in order to prevent an endangering of the patients and a contamination of wetted areas . It has been looked for a method of decontamination which could be used under practical conditions . The experimentally contaminated taps could be disinfected in a short time when hot water was lead into the taps . The taps could not be disinfected by heating with a flexible electric heating ribbon. J Inorg Biochem, 1986 Oct-Nov, 28(2-3), 329 - 36 Isolation and properties of the complex nonheme-iron-containing cytochrome b557 (bacterioferritin) from Pseudomonas aeruginosa; Moore GR et al.; A nonheme-iron-containing cytochrome b557, also known as bacterioferritin, was isolated from Pseudomonas aeruginosa . Gel electrophoresis showed that the protein subunits had a molecular weight of 18 kD and it is suggested that the intact molecule contained 24 subunits . The isolated protein contained 8.7% by weight Fe and 8% by weight phosphate . Most of the Fe was contained in the nonheme-iron core and could be readily removed by dialysis against 0.12 M thioglycollic acid . The resulting apobacterioferritin contained approximately one protoporphyrin IX group for every five subunits and, in addition, an unidentified fluorophor . The nonheme-iron core was found to be amorphous with a mean core size of 60-65 A. Biochem Int, 1986 Oct, 13(4), 547 - 53 Genes encoding threonine tRNAs with the anticodon CGU from Escherichia coli and Pseudomonas aeruginosa; Dalrymple B et al.; Homologous genes for threonine tRNAs with the anticodon CGU have been identified in the region of the proBA operon of Escherichia coli and downstream from the fimbrial subunit gene of Pseudomonas aeruginosa . tRNAs with the anticodon CGU have not previously been identified from either of these bacterial species . Sequence analyses have shown that these genes are similar to other bacterial tRNA genes, and that the predicted structure conforms to the standard cloverleaf model, including retention of all invariant and semi-invariant bases . Analysis of upstream sequences suggests that these genes have associated promoters and are probably expressed in vivo. Zh Mikrobiol Epidemiol Immunobiol, 1986 Oct, (10), 72 - 5 {Development of a polyvalent erythrocyte diagnostic agent based on the antigens of Pseudomonas aeruginosa slime}; Aleksandrova IA et al.; The study has revealed the fundamental possibility, and established the concrete conditions of obtaining standard erythrocyte polyvalent diagnosticum for the detection of antibodies to the antigens of P . aeruginosa, belonging to 5 types most frequently occurring in clinical practice, in the passive hemagglutination test . The data on high type- and species-specificity of the new erythrocyte diagnosticum have been obtained, which indicates that slime antigens have been correctly chosen as sensitins and confirms the necessity of using the polyvalent preparation . Preliminary data on the clinical trial of the erythrocyte diagnosticum show the expediency of its use for the control of specific immune response in donors in the process of obtaining anti-P . aeruginosa hyperimmune plasma, as well as the possibility of using this method for the serological diagnosis of P . aeruginosa infection . The diagnostic preparation has been found to retain its activity for 10 months (the term of observation). Antimicrob Agents Chemother, 1986 Oct, 30(4), 584 - 9 Effect of clavulanic acid on the activity of ticarcillin against Pseudomonas aeruginosa; Tausk F et al.; We studied the ability of clavulanic acid (CA) to induce beta-lactamase in Pseudomonas aeruginosa isolates and what effect this might have on the susceptibilities to beta-lactam agents . We first used a disk approximation method to test 4 laboratory and 16 clinical P . aeruginosa isolates against antipseudomonal beta-lactam agents for truncation by CA and found this to be very common . All antimicrobial compounds except imipenem demonstrated truncation in the vicinity of CA . We also evaluated the extent to which chromosomal beta-lactamase is induced by CA and found this to occur to some degree in most isolates and to be dependent on the concentration of CA . Finally, we performed time kill curves on these isolates to compare bacterial growth in ticarcillin alone with growth in ticarcillin-CA (the CA at 2 or 4 micrograms/ml) . We found that CA at this concentration has neither an antagonistic nor a synergistic antibacterial effect in combination with ticarcillin. Antibiot Med Biotekhnol, 1986 Oct, 31(10), 778 - 81 {Treatment of an infection due to the intraperitoneal inoculation of mice with Pseudomonas aeruginosa with tobramycin and hyperimmune Pseudomonas aeruginosa plasma used per se and in combination}; Minukhin VV et al.; Schemes for treating infections caused by intraperitoneal administration of P . aeruginosa to mice were tested . The animals were treated with tobramycin and hyperimmune pyocyanic plasma (HPP) used per se or in combination . In a dose of 5 mg/kg body weight tobramycin protected 72.9 per cent of the animals from death . HPP with a titer of the antipyocyanic antibodies of 1:320-1:160 had a stable 100 per cent protective effect on the infected animals . However, no complete elimination of P . aeruginosa from the host was observed . The combined use of tobramycin and HPP LD50 protected 97.23 per cent of the mice from lethal infection, the drugs being titrated for their separate use . The combined administration of tobramycin and HPP in treatment of mice with acute infection due to P . aeruginosa was more efficient than their use alone. J Clin Pathol, 1986 Oct, 39(10), 1124 - 9 Development of enzyme linked immunosorbent assay (ELISA) to detect antibodies to Pseudomonas aeruginosa cell surface antigens in sera of patients with cystic fibrosis; Brett MM et al.; An enzyme linked immunosorbent assay (ELISA) to measure free serum IgG antibodies to Pseudomonas aeruginosa in patients with cystic fibrosis was developed . Seven strains of P aeruginosa cells, treated with glutaraldehyde and representing the most commonly isolated serotypes in our cystic fibrosis unit, were used . The specificity of the test was confirmed by the absence of cross reacting antibodies to other Gram negative bacteria . The results showed differences in the titres of antibodies at different stages of P aeruginosa infection . Because of its reproducibility, specificity, and sensitivity these preliminary results suggest that this test may be of value in monitoring the progress of P aeruginosa infection in patients with cystic fibrosis. J Antibiot (Tokyo), 1986 Oct, 39(10), 1419 - 29 Studies on 6 alpha-substituted penicillins . II . Synthesis and structure-activity relationships of 6 beta-(2-aryl-2-sulfoacetamido)-6 alpha-methoxy penicillanic acids; Burton G et al.; The synthesis and antibacterial activity of 6 alpha-methoxysulbenicillin analogues (2) are described . Structure-activity studies of these derivatives bearing hydrophilic substituents in the phenyl ring led to the identification of disodium 6 beta-{D-2-(3,4-dihydroxyphenyl)-2-sulfoacetamido}-6 alpha-methoxypenicillanate (2m) as a compound with potent activity against Pseudomonas aeruginosa including beta-lactamase producing strains . Additional substitution of 2m gave derivatives 2p, 2q, 2r, with a further improvement in activity against Gram-negative bacteria. Microbiologica, 1986 Oct, 9(4), 455 - 60 Evaluation of Pseudomonas aeruginosa influence on the cytoskeleton of Hep-2 cells; Zanetti S et al.; The cell cytoskeleton (microtubules, microfilaments and intermediate filaments) plays an important role in many cell functions, such as maintenance of cell locomotion, movement and compartimentalization of intracellular organelles and cell-to-cell interaction . Therefore, cytoskeleton alterations may result in sever impairment of cell functions . The aim of this paper was to study the in vitro effects of Pseudomonas aeruginosa on the cytoskeleton of cultivated Hep-2 cells . Cytoskeleton modifications were evidenced by immunofluorescence using monoclonal and polyclonal antibodies against tubulin and vimentin, and rhodamine conjugated phalloidin, that specifically binds to actin microfilaments . We report here that P . aeruginosa has a strong cytopathic effect on monolayers within a few hours of contact with the cells, and influences the organization of microfilaments, but has no discernable effect on microtubules or intermediate filaments. J Antimicrob Chemother, 1986 Oct, 18(4), 453 - 8 Incidence of strains producing plasmid determined beta-lactamases among carbenicillin resistant Pseudomonas aeruginosa; Tirado M et al.; A total of 1056 strains of Pseudomonas aeruginosa isolated from human clinical specimens from patients was collected from eight laboratories in order to study the frequency of plasmid-determined beta-lactamase producers and the different enzymes represented . The strains from each laboratory comprised consecutive, non-repeated, clinical isolates . In the 166 strains selected because they were carbenicillin resistant, the isoelectric points of the beta-lactamases were studied by means of analytical isoelectric focusing and the different types of plasmid-determined beta-lactamases identified . Seventy-five of the strains (45.18%) were plasmid-mediated beta-lactamase producers; the frequency varied among laboratories from 0% to 100% . Overall the most frequently identified beta-lactamase type was PSE-1 (49.34%) followed by TEM-1 (37.34%) . The remaining carbenicillin-resistant strains did not produce plasmid-determined beta-lactamases. Arch Ophthalmol, 1986 Oct, 104(10), 1540 - 4 Quantitation of corneal inflammation by chemiluminescense; Chusid MJ et al.; Various inflammatory agents, including Pseudomonas aeruginosa, bacterial filtrates, endotoxin, and phorbol myristate acetate were found to induce significant increases in corneal chemiluminescense (CLM) . Disruption of polymorphonuclear leukocytes within corneas by sonication, freeze-thawing or cryotherapy, or reduction of corneal infiltration by induction of neutropenia resulted in marked decreases of CLM . Increased corneal CLM was associated with significant increases in corneal thickness and water content . Oxygen-free radical scavengers significantly inhibited CLM of experimentally infected corneas in vitro, as did the anti-inflammatory agents prednisolone acetate, indomethacin, and salicylic acid . In vivo therapy of infected corneas with prednisolone resulted in significant reductions in corneal CLM, thickness, and water content compared with saline-treated eyes . The CLM assay is a simple technique that allows quantitation of corneal inflammation and evaluation of the effect of therapeutic agents on corneal inflammation. Infect Immun, 1986 Oct, 54(1), 239 - 44 Polyclonal and monoclonal antibody therapy for experimental Pseudomonas aeruginosa pneumonia; Pennington JE et al.; A human immunoglobulin G preparation, enriched in antibodies to lipopolysaccharide (LPS) Pseudomonas aeruginosa antigens (PA-IGIV) and murine monoclonal antibodies (MAb) to P . aeruginosa Fisher immunotype-1 (IT-1) LPS antigen and outer membrane protein F (porin), were evaluated for therapeutic efficacy in a guinea pig model of P . aeruginosa pneumonia . The concentration of antibodies to IT-1 LPS was 7.6 micrograms/ml in PA-IGIV and 478 micrograms/ml in the IT-1 MAb preparation . No antibody to IT-1 was detected in MAb to porin . For study, animals were infected by intratracheal instillation of IT-1 P . aeruginosa and then treated 2 h later with intravenous infusions of PA-IGIV, IT-1 MAb, or porin MAb . Control groups received intravenous albumin, and routinely died from pneumonia . Both PA-IGIV (500 mg/kg) and IT-1 MAb (greater than or equal to 2.5 mg/kg) treatment resulted in increased survival (P less than 0.01 to 0.001), and also improved intrapulmonary killing of bacteria . Porin MAb failed to protect from fatal pneumonia . IT-1 MAb treatment produced more survivals than did PA-IGIV treatment but only at dosages of MAb resulting in serum antibody concentrations greater than those achieved with PA-IGIV . PA-IGIV and IT-1 MAb demonstrated in vitro and in vivo (posttreatment guinea pig serum) opsonophagocytic activity for the IT-1 challenge strain . However, the polyclonal preparation required complement, whereas the MAb did not . We conclude that passive immunization with polyclonal hyperimmune P . aeruginosa globulin or with MAb to LPS antigens may be useful in the treatment of acute P . aeruginosa pneumonia . The relative efficacies of such preparations may be limited, however, by their type-specific LPS antibody concentrations. Infect Immun, 1986 Oct, 54(1), 149 - 53 Degradation of soluble laminin and depletion of tissue-associated basement membrane laminin by Pseudomonas aeruginosa elastase and alkaline protease; Heck LW et al.; Purified Pseudomonas aeruginosa elastase and alkaline protease rapidly cleaved soluble laminin, with each enzyme yielding different cleavage products . These cleavage fragments were separated from the intact laminin A and B polypeptide chains by sodium dodecyl sulfate-polyacrylamide gradient gel electrophoresis and detected by their characteristic Coomassie blue staining patterns . Pseudomonas elastase produced rapid and extensive degradation of both A and B chains, including the disulfide-rich regions . Apparently complete degradation to limit digests was obtained after 30 min with a substrate/enzyme ratio of 30:0.5 . Under similar conditions, alkaline protease rapidly degraded the A chain while slowly degrading the B chain . In addition, immunoreactive laminin was released from authentic basement membranes after incubation with either enzyme as detected by an enzyme-linked immunoabsorption assay and by immunofluorescence . The results from these studies suggest a direct role for elastase and alkaline protease in both tissue invasion and hemorrhagic tissue necrosis in P . aeruginosa infections. J Infect Dis, 1986 Oct, 154(4), 682 - 8 Pseudomonas aeruginosa polysaccharide-tetanus toxoid conjugate vaccine: safety and immunogenicity in humans; Cryz SJ Jr et al.; A Pseudomonas aeruginosa polysaccharide-tetanus toxoid (Ttxd) conjugate vaccine was produced . Polysaccharide was derived from lipopolysaccharide (LPS) and covalently linked to Ttxd by using carbodiimide with adipic acid dihydrazide as a spacer molecule . The conjugate possessed a relative molecular weight of greater than 350,000 and was nontoxic and nonpyrogenic . The vaccine bound serospecific monoclonal antibodies with an avidity similar to LPS and reacted with murine and human opsonic antibody . The vaccine was immunogenic in rabbits and mice and elicited IgG antibody to both LPS and Ttxd . The vaccine was safe when parenterally administered to humans and evoked only mild, transient reactions . Mean titers of IgG antibody to LPS rose 19-fold after immunization, with 82% of the volunteers responding with a fourfold or greater rise in titer . IgG antibody to LPS evoked after immunization was opsonic and highly effective at preventing fatal experimental burn wound sepsis due to P . aeruginosa. J Gen Microbiol, 1986 Oct, 132 ( Pt 10), 2667 - 75 The arcABC operon required for fermentative growth of Pseudomonas aeruginosa on arginine: Tn5-751-assisted cloning and localization of structural genes; Luthi E et al.; Pseudomonas aeruginosa is able to utilize L-arginine as the energy source for growth under anaerobic, nitrate-free conditions . Mutations in the chromosomal arcABC gene cluster specifying the inducible arginine deiminase pathway enzymes abolish fermentative growth on arginine . From two different arc::Tn5-751 insertion mutants of P . aeruginosa recombinant plasmids have been derived which carry a resistance marker of transposon Tn5-751 plus flanking parts of the arc region . These recombinant plasmids served to reconstruct in vitro the functional arcABC cluster on a 5.6 kb fragment, which was inserted into the broad-host-range vector pKT240 . In P . aeruginosa this 5.6 kb segment complemented arcABC mutations in trans and contained the control region necessary in cis for arc enzyme induction by oxygen limitation and arginine . The results of subcloning experiments and transcriptional lacZ fusions, the polarity of transposon insertions and the effect of external promoters led to the conclusion that the structural genes arcA (for arginine deiminase), arcB (for catabolic ornithine carbamoyltransferase) and arcC (for carbamate kinase) are contiguous and transcribed in the same direction . Thus, the arcABC cluster appears to have the characteristics of an operon . In Escherichia coli the cloned arcABC genes were expressed at low, non-inducible levels; strong vector promoters enhanced arc expression up to 100-fold . This indicates that transcriptional initiation at the arc promoter(s) is poor in E . coli. Eur J Biochem, 1986 Oct 1, 160(1), 149 - 53 Pseudomonas aeruginosa cytochrome oxidase . Product inhibition by low thermodynamic driving force; Blatt Y et al.; The steady-state kinetics of Pseudomonas aeruginosa cytochrome oxidase were studied . Reduced cytochrome c551 and azurin from the same bacteria were used as the electron-donating substrates, while dioxygen served as the electron acceptor . Oxidized cytochrome c551 and azurin exhibited product inhibition of the reaction . However, apo-azurin and azurin derivatives in which the copper was substituted by the redox-inert ions Ni2+, Co2+, Cd2+ and Zn2+, did not show any effect on the kinetics . These observations implied that complex formation between the substrates or the products and the enzyme is not a rate-limiting step and is not the cause for product inhibition . The integrated rate law for a reaction scheme in which we assumed that complex formation was not rate limiting was fitted to the complete reaction traces . The results suggested that it is the low thermodynamic driving force, expressed in the small differences in redox potential between the substrates and heme c of the enzyme, which cause the observed product inhibition. Mol Gen Mikrobiol Virusol, 1986 Oct, (10), 13 - 6 {Physical map of Pseudomonas aeruginosa phage phi kF77 genome . Localization of sites sensitive to restriction endonucleases}; Kulakov LA et al.; A physical map of the P . aeruginosa bacteriophage phi kF77 has been constructed using the restriction endonucleases SalI, HindIII, EcoRI, EcoRV, MuI, XbaI, ClaI . The phi kF77 DNA is resistant to cleavage by the restriction endonucleases BamHI, BglII, HpaI, PstI, PvuII, SmaI, XhoI. Bioorg Khim, 1986 Oct, 12(10), 1422 - 4 {Structure of O-specific polysaccharide chains of Pseudomonas aeruginosa II (Sandwick) and V (Verder-Evans) lipopolysaccharides containing N-acetyl-D-galactosaminuronic acid}; Knirel' IuA et al.; Acidic polysaccharides were isolated from the Pseudomonas aeruginosa II (Sandvik) and V (Verder-Evans) lipopolysaccharides on mild acid hydrolysis followed by gel filtration on Sephadex G-50 . The Sandvik II polysaccharide consists of 2-acetamido-2-deoxy-D-galacturonic acid, 2-acetamido-2,6-dideoxy-D-glucose, and L-rhamnose in the ratio 1:1:2 . The Verder-Evans V polysaccharide contained the same monosaccharides and, in addition, a D-glucose residue . On the basis of 13C NMR data, methylation analysis, Smith degradation and solvolysis with hydrogen fluoride, the following structures were determined for the repeating units of the polysaccharides: (Formula: see text). Bioorg Khim, 1986 Oct, 12(10), 1384 - 90 {Antigenic polysaccharides of bacteria . 18 . Structure of O-specific polysaccharide chains of Pseudomonas aeruginosa 05 (Lányi) lipopolysaccharide}; Knirel' IuA et al.; Polysaccharide chains of P . aeruginosa O5a, b, c, O5a, b, d and O5a, d (Lanyi classification) lipopolysaccharides contain D-xylose, N-acetyl-D-fucosamine (FucNAc) and a derivative of 5,7-diamino-3,5,7,9-tetradeoxy-L-glycero-L-manno-nonulosonic acid (pseudaminic acid, PseN2) carrying acetyl or (R)-3-hydroxybutyryl (Hb) and formyl (Fm) groups as N-acyl substituents . Degradation of the lipopolysaccharides with dilute acetic acid caused depolymerisation of the polysaccharide chains as a result of cleavage of glycosidic linkage of pseudaminic acid to give trisaccharides representing chemical repeating units of the polysaccharides . Basing on analysis of the trisaccharides using 1H and 13C NMR spectroscopy and mass-spectrometry, the following structures of the polysaccharide chains were established: (Formula: see text) . O5a, d polysaccharide is identical to P . aeruginosa immunotype 6 O-specific polysaccharide. Biochim Biophys Acta, 1986 Sep 26, 873(2), 214 - 27 The pH and redox-state dependence of the copper site in azurin from Pseudomonas aeruginosa as studied by EXAFS; Groeneveld CM et al.; The EXAFS of the K-edge of copper in azurin from Pseudomonas aeruginosa has been measured in solutions of the oxidized and reduced protein, at both low and high pH . Model compounds of known molecular structure, exhibiting Cu-N and Cu-S bonds of varying length, were studied as well . The major shell of the high-pH oxidized azurin EXAFS contains contributions of two N(His) at 1.95 +/- 0.03 A, and one S(Cys) at 2.23 +/- 0.03 A . Some minor contributions from the carbon atoms of the histidine residues and the distal sulfur atom are observed in the 3-4 A region . Upon reduction a decrease is seen in amplitude of the main peak in the Fourier transform, due to a lengthening of one of the Cu-N(His) bonds (2.05 +/- 0.03 A), and a shortening of the other (1.89 +/- 0.03 A), both by approx . 0.1 A . Indications for a Cu-S(Met) bond are found in the reduced azurin data (2.70 +/- 0.05 A) . However, in the oxidized protein, this bond could not be determined unambiguously, in line with results of a model compound featuring weak Cu-thioether coordination . The effect of pH is only slight for both the oxidized and the reduced protein, and no significant changes in bond lengths are found upon a change of pH from 4.1 to 9.1 . The relevance of these findings for the interpretation of the existing data on the redox activity of the protein is discussed. Presse Med, 1986 Sep 20, 15(30), 1417 - 20 {Antibiotic therapy of Pseudomonas aeruginosa infections}; Modai J et al.; Antibiotics active against Pseudomonas aeruginosa are carboxy- and ureidopenicillins, some cephalosporins, aztreonam, imipenem, aminoglycosides, fluoroquinolones and, in some special circumstances, polymyxins and fosfomycin . The choice of the antibiotic should be based not only on minimal inhibitory concentrations in vitro, but also on the inoculum effect, on the speed with which bacteria are killed, on natural or acquired resistance and on data obtained from experimental infections in animals . Antibiotics used against P . aeruginosa infections must be rapidly bactericidal . Since the prognosis is severe, the initial treatment given before the sensitivity of the strain is known must combine a beta-lactam antibiotic and an aminoglycoside, both being selected among the most regularly active. J Immunol, 1986 Sep 15, 137(6), 2025 - 30 In vitro T cell-mediated killing of Pseudomonas aeruginosa . IV . Nonresponsiveness in polysaccharide-immunized BALB/c mice is attributable to vinblastine-sensitive suppressor T cells; Powderly WG et al.; We reported previously that BALB/c mice immunized with a polysaccharide (PS) antigen isolated from immunotype 1 Pseudomonas aeruginosa and vinblastine sulfate develop T cell-mediated protective immunity, despite their failure to produce specific antibody . In vitro, Lyt-1-,2+, I-J+ T cells from vinblastine- and PS-immunized mice kill P . aeruginosa by secretion of a bactericidal lymphokine . BALB/c mice immunized with PS alone generate neither protective antibodies nor a protective T cell response . The current studies indicate that T cells from mice immunized with PS alone significantly suppress the bactericidal activity of T cells from mice immunized with vinblastine and PS . The suppressor T cells are of the same Lyt-1-,2+, I-J+ phenotype as the bactericidal T cells . Suppression is mediated by a soluble product of these suppressor T cells which both inhibits T cell proliferation and interferes with the production or release of the bactericidal lymphokine . Cyclophosphamide, used in other systems to remove suppressor T cells, fails to enhance bacterial killing and does not inhibit suppressor cell activity . These studies indicate that immunization with PS elicits responses in two functionally distinct subgroups of Lyt-1-,2+, I-J+ T cells, and that these cells are distinguishable by their sensitivity to vinblastine sulfate. Biochim Biophys Acta, 1986 Sep 11, 860(3), 699 - 707 Demonstration and chemical modification of a specific phosphate binding site in the phosphate-starvation-inducible outer membrane porin protein P of Pseudomonas aeruginosa; Hancock RE et al.; The interaction of phosphate ions with the Pseudomonas aeruginosa anion-specific protein P channel was probed . The single-channel conductance of protein P incorporated into planar lipid bilayer membranes in the presence of 0.3 M H2PO-4 was shown to be 6.0 pS, demonstrating that protein P channels allowed the permeation of phosphate . When large numbers of protein P channels were incorporated into lipid bilayer membranes in the presence of 40 mM Cl-, addition of small concentrations of phosphate resulted in reduction of macroscopic Cl- conductance in a dose- (and pH-) dependent fashion . This allowed calculation of an I50 value of e.g . 0.46 mM at pH 7.0, suggesting that the affinity of protein P for its normal substrate phosphate was at least 60-100-fold greater than the affinity of the channel for other ions such as chloride . Pyrophosphate and the phosphate analogue, arsenate, also inhibited macroscopic Cl- conductance through protein P with I50 values at pH 7.0 of 4.9 mM and 1.3 mM, respectively . To probe the nature of the phosphate binding site, the epsilon-amino groups of available lysine residues of protein P were chemically modified . Acetylation and carbamylation which produced uncharged, modified lysines destroyed both the anion (e.g . Cl-) binding site and the phosphate binding site as determined by single-channel experiments and macroscopic conductance inhibition experiments respectively . Nevertheless, the modified proteins still retained their trimeric configuration and their ability to reconstitute single channels in lipid bilayer membranes . Methylation, which allowed retention of the charge on the modified lysine residues, increased the Kd of the channel for Cl- 33-fold and the I50 for phosphate inhibition of macroscopic Cl- conductance 2.5-4-fold . A molecular model for the phosphate binding site of the protein P channel is presented. Klin Monatsbl Augenheilkd, 1986 Sep, 189(3), 240 - 2 {Studies of the penetrating ability of fosfomycin into the aqueous humor and vitreous body of the eye}; Philipp W et al.; Fosfomycin is an antibiotic with a new simple chemical structure and a broad spectrum of antibacterial activity, especially against staphylococci . In the study reported here, the penetration of fosfomycin into the aqueous humor and vitreous body was investigated after intravenous infusion of 4 and 8 g . The highest average concentration approximately 2 hours after administration was 28.3 micrograms/ml after the 4 g dose and 52 micrograms/ml after the 8 g dose . Both the 4 g and 8 g doses thus produced aqueous humor levels exceeding the minimum inhibitory concentrations required for most gram-positive and gram-negative organisms commonly responsible for bacterial endophthalmitis, including strains of pseudomonas aeruginosa . Extremely high aqueous humor levels of fosfomycin were observed in two patients with inflamed eyes because of a change in the blood-aqueous barrier. J Antibiot (Tokyo), 1986 Sep, 39(9), 1243 - 56 Semisynthetic beta-lactam antibiotics . III . Synthesis and antibacterial activity of 7 beta-{2-(2-aminothiazol-4-yl)-2-(substituted carbamoylmethoxyimino)acetamido}cephalosporins; Arimoto M et al.; Syntheses of cephalosporins modified with a 7 beta-{2-(2-aminothiazol-4-yl)-2-(substituted carbamoylmethoxyimino)acetamido} group at the C-7 position and with various hetero aromatics at the C-3 position are described . The effects of substituents on the carbamoyl group in the 7-side chain were investigated in order to improve antibacterial activity . Some of these compounds exhibited high antibacterial activity against Gram-positive and Gram-negative bacteria, including Pseudomonas aeruginosa, as well as good resistance to beta-lactamase. Am J Reprod Immunol Microbiol, 1986 Sep, 12(1), 21 - 4 Bacteriology of cervix in cases of infertility: effect on human sperm; Kaur M et al.; Microorganisms such as Escherichia coli, Pseudomonas aeruginosa, and Bacillus subtilis isolated from cervices of infertile females possessed spermicidal activity . They also agglutinated the human spermatozoa in vitro and showed tail-to-tail agglutination . Cell-free supernatant of these organisms was found to be spermicidal but did not agglutinate spermatozoa in vitro . Spermicidal activity was increased with increase in age of the culture. Laryngoscope, 1986 Sep, 96(9 Pt 1), 1021 - 3 Malignant external otitis with optic neuritis; Holder CD et al.; Malignant external otitis (MEO) is a progressive necrotizing infection which spreads to the skull base . The causative organism is usually Pseudomonas aeruginosa and 90% of the patients are diabetic . The infection gains access to the skull base at the temporal bone . Cranial nerve involvement is common . We present a case of malignant external otitis causing blindness due to optic neuritis . Progressive vascular involvement along the skull base is the pathogenic mechanism that best explains spread from the temporal bone to the orbital apex. Infection, 1986 Sep-Oct, 14(5), 246 - 9 Fosfomycin-ampicillin versus gentamicin-ampicillin in the treatment of critically ill patients with pneumonia; Nissen LR et al.; Thirty-two patients with severe pneumonia (22 on assisted ventilation) were entered into a prospective randomised trial, in which fosfomycin plus ampicillin (17 patients) was compared with gentamicin plus ampicillin (15 patients) . Treatment was either 4 g fosfomycin or 80 mg gentamicin every 8 h and 1 g ampicillin every 6 h . Complete or partial clinical success was attained in 94% (16/17) in the fosfomycin group and in 80% (12/15) in the gentamicin group . Bacteriological success was 87.5% with fosfomycin-ampicillin and 90% with gentamicin-ampicillin . An intermediary sensitive Klebsiella pneumoniae strain developed complete resistance in the fosfomycin group, and an in vitro sensitive Pseudomonas aeruginosa strain was resistant in vivo in the gentamicin group . Two of three patients in the fosfomycin group receiving the infusion through a peripheral vein developed thrombophlebitis . No other side-effects were observed . We conclude that fosfomycin is at least as effective as gentamicin . Since fosfomycin is widely atoxic and may be given in large doses, irrespective of kidney function, it is considered to have advantages over gentamicin in the combined therapy of pneumonia. Antimicrob Agents Chemother, 1986 Sep, 30(3), 435 - 9 Antibiotic-resistant bacteria in surveillance stool cultures of patients with prolonged neutropenia; Wingard JR et al.; The value of stool surveillance for antibiotic-resistant gram-negative bacteria was analyzed in 86 neutropenic bone marrow transplant patients . Twice-weekly specimens were inoculated onto culture medium containing gentamicin plus carbenicillin . The recovered organisms were identified to the species level and tested for antibiotic susceptibility . Forty-eight resistant organisms were recovered from 35 patients . Thirteen isolates persistently colonized patients . Escherichia coli (29%) and Pseudomonas aeruginosa (19%) were the most frequently recovered organisms . Although most organisms were recovered while patients were on antibiotics, 15 isolates, including eight of nine resistant P . aeruginosa, were detected before antibiotics were initiated . The duration of antibiotic use was longer for patients persistently colonized than for those not colonized (P = 0.03) . Of the 15 resistant organisms which caused infection, 12 were detected in the surveillance cultures . Infections by antibiotic-resistant organisms occurred more frequently in patients colonized than in those not colonized (P = 0.006) and more frequently in patients persistently colonized than in those colonized only once (P = 0.01) . The absence of colonization or persistent colonization correlated well with the absence of infection (negative predictive values of 94 and 91%, respectively). Pediatr Med Chir, 1986 Sep-Oct, 8(5), 715 - 20 {Occurrence of hospital infections in a department of pediatric heart surgery}; Mantero E et al.; The incidence of nosocomial infections (NI) and the related risk factors in a Department of Pediatric Cardiovascular Surgery were studied, during a 6 months period . 155 successive admissions were considered . Nosocomial infections were 17 (11%), nosocomial colonizations 18 (11.6%) . The most important risk factors for nosocomial infections were: age, cyanosis, duration of hospitalization, hospitalization in Intensive Care Unit and central venous catheter only as a risk factor for sepsis . The most important risk factors for nosocomial colonizations were: tracheal intubation and central venous catheter . In 4 cases the NI was related to nosocomial colonization (2 sepsis, 1 pneumonia, 1 wound infection) . The most frequently isolated microorganisms were Pseudomonas aeruginosa and Staphylococcus spp . The Authors found that a longer than 5 days period of antibiotic prophylaxis did not reduce the incidence of nosocomial infections. Pathol Biol (Paris), 1986 Sep, 34(7), 855 - 8 {Choice of a rapidly bactericidal beta-lactamin-aminoglycoside combination in the treatment of Pseudomonas aeruginosa infections at a child intensive care unit}; Lambert-Zechovsky N et al.; Morbidity and mortality among children with Pseudomonas aeruginosa infection in Pediatric Intensive Care Unit remains high . Delays in bacterial killing may be responsible for the poor outcome . Antimicrobial sensitivity and timed-killing assays were determined for ticarcillin, azlocillin, piperacillin, cefsulodin, ceftazidime, gentamicin, tobramycin and amikacin alone and in combination against 40 strains of Pseudomonas aeruginosa isolated from blood cultures and tracheal aspirate . Antibiotic concentrations used were at clinically achievable level . None bactericidal effect was observed with each beta-lactamin alone . However with the combinations azlocillin or piperacillin or cefsulodin or ceftazidime plus amikacin a bactericidal effect was observed at 4.5 hours. Mol Biol Evol, 1986 Sep, 3(5), 449 - 58 Structure and regulation of the anthranilate synthase genes in Pseudomonas aeruginosa: II . Cloning and expression in Escherichia coli; Crawford IP et al.; The genes for the large and small subunits of anthranilate synthase (trpE and trpG, respectively) have been cloned from Pseudomonas aeruginosa PAC174 into E . coli by R-prime formation with the broad-host-range plasmid R68.44 . Sequential subcloning into plasmid vectors reduced the active Pseudomonas DNA fragment to a length of 3.1 kb . We obtained evidence that this region contains the promoter for its own expression and retains a vestigial regulatory response to tryptophan scarcity or excess. Mol Biol Evol, 1986 Sep, 3(5), 436 - 48 Structure and regulation of the anthranilate synthase genes in Pseudomonas aeruginosa: I . Sequence of trpG encoding the glutamine amidotransferase subunit; Crawford IP et al.; We have determined the DNA sequence of the distal 148 codons of trpE and all of trpG in Pseudomonas aeruginosa . These genes encode, respectively, the large and small (glutamine amidotransferase) subunits of anthranilate synthase, the first enzyme in the tryptophan synthetic pathway . The sequenced region of trpE is homologous with the distal portion of E . coli and Bacillus subtilis trpE, whereas the trpG sequence is homologous to the glutamine amidotransferase subunit genes of a number of bacterial and fungal anthranilate synthases . The two coding sequences overlap by 23 bp . Codon usage in these Pseudomonas genes shows a marked preference for codons ending in G or C, thereby resembling that of trpB, trpA, and several other chromosomal loci from this species and others with a high G + C content in their DNA . The deduced amino acid sequence for the P . aeruginosa trpG gene product differs to a surprising extent from the directly determined amino acid sequence of the glutamine amidotransferase subunit of P . putida anthranilate synthase (Kawamura et al . 1978) . This suggests that these two proteins are encoded by loci that duplicated much earlier in the phylogeny of these organisms but have recently assumed the same function . We have also determined 490 bp of DNA sequence distal to trpG but have not ascertained the function of this segment, though it is rich in dyad symmetries. Quad Sclavo Diagn, 1986 Sep, 22(3), 273 - 82 {Frequency of isolation and drug resistance of bacterial strains isolated from respiratory material in patients with cystic fibrosis}; Rosselli P; During 1985, 251 respiratory samples from 61 patients were examined at the tuscan cystic fibrosis Center (Florence), and isolated strains were tested against various antimicrobial drugs . Pseudomonas aeruginosa and Staphylococcus aureus were the predominant pathogens isolated . Infections caused by St . aureus were the commonest during the first years of life, whereas those caused by Ps . aeruginosa, occasional at early age, became chronic and the main source of infection with growth . Sensitivity testings against antibiotics confirmed that Ps . aeruginosa isolated from cystic fibrosis patients has a high percentage of resistant strains . The most active drugs were ceftazidime and aztreonam . An increased resistance to aminoglycosides was observed. Acta Paediatr Scand, 1986 Sep, 75(5), 840 - 5 Does centralized treatment of cystic fibrosis increase the risk of Pseudomonas aeruginosa infection? Pedersen SS, Jensen T, Pressler T, Hoiby N, Rosendal K. Two hundred and forty Danish patients with cystic fibrosis (97% of the total CF population in Denmark) participated in a point-prevalence study of Pseudomonas aeruginosa infection . One hundred and ninety-two patients were treated at the Danish CF centre and 48 patients were treated in other places . The age distribution was significantly different as no patients older than 19 years were found in the non-centre group . Pathogenic bacteria were isolated from the sputum of 96% of the patients . P . aeruginosa was more prevalent in patients from the centre, whereas Staphylococcus aureus was more prevalent in the non-centre group . No difference in serogroup and phage pattern of P . aeruginosa was found . There was a tendency that non-centre treated patients acquired chronic broncho-pulmonary P . aeruginosa infection later, but at the age of 16 years 90% of all patients will be chronically infected . Chronic P . aeruginosa infection was significantly more common in the age group 10-14 years at the centre than outside the centre . It is not possible to prevent chronic P . aeruginosa infection in CF patients treated in small groups and because of the better prognosis of centralized treatment the latter must be recommended. Jpn J Antibiot, 1986 Sep, 39(9), 2355 - 66 {Cefsulodin concentration in exudates from drainage of patients with acute peritonitis following intravenous administration}; Nakamura T et al.; Cefsulodin (CFS), a new antipseudomonal cephalosporin, shows a potent antibacterial activity against Pseudomonas aeruginosa and some Gram-positive bacteria, whereas it shows low activity against many Gram-negative rods . Against clinical isolates of P . aeruginosa, CFS was about 10 times more active than sulbenicillin and carbenicillin, and had a similar activity to gentamicin and dibekacin . The CFS was administered by an intravenous bolus injection at a dose of 1 g to each of 14 patients operated for acute peritonitis with drainage or radical mastectomy with drainage to treat breast cancer . These cases included 3 of localized peritonitis due to perforative appendicitis, 3 of diffuse peritonitis due to perforative duodenal ulcer, 2 of panperitonitis due to intestinal obstruction and perforative sigmoid colon cancer, 4 of subacute cholangitis, localized peritonitis T-tube choledochal drainage due to choledocholithiasis, and 2 of breast cancer . Materials from drain exudate were taken at intervals with sterilized paper discs and CFS concentrations were determined by the paper disc bioassay method with P . aeruginosa NCTC 10490 as the test organism . Serum concentrations of CFS just after injection reached 135.4 +/- 66.1 micrograms/ml, and they were 2.7 +/- 1.5 micrograms/ml at 6 hours after injection . Concentrations in purulent exudates of patients with acute peritonitis increased quickly after intravenous bolus injections, and reached maximum levels relatively early after injection in cases 2 to 3 days after operation . In cases 10 to 13 days after operation, CFS levels were comparatively low and reached to peak levels at 4 to 5 hours after injection . Levels of CFS in purulent exudate tended to increase in proportion to the severity of symptoms, as did CFS levels in appendix wall . Pseudomonas spp . were not isolated in this study, but MICs of CFS were mostly around 1.56 to 3.13 micrograms/ml when clinically isolated Pseudomonas spp . were present at 10(6) cells/ml . Levels of CFS in infected exudate were higher than the above MIC values against Pseudomonas spp . Therefore, CFS were a useful drug for the chemotherapy against pseudomonal infections. Eur J Epidemiol, 1986 Sep, 2(3), 182 - 5 Prevalence of protease and elastase production by clinical isolates of Pseudomonas aeruginosa in relation to aeruginocine typing patterns; Kapur R et al.; Sixty six consecutive P . aeruginosa isolates from heterogeneous clinical specimens were subjected to aeruginocine (pyocine) typing and assayed for in vitro protease and elastase production by a simple and reproducible qualitative test . The 45.4% of the clinical isolates were found to be both protease and elastase (P + E +) producers; 40.9% were only protease producers (P + E -) and 13.6% were non producers (P - E -) . Aeruginocine code 7777 strains were found to be predominant among P + E + and P + E - types, as 48.2% and 51.7% isolates belonged to the types, respectively, suggesting thereby the virulence of this aeruginocine type in P . aeruginosa infections and the possible association of protease and elastase production with aeruginocine production. Arch Microbiol, 1986 Sep, 145(4), 408 - 10 Alginate biosynthesis by Pseudomonas aeruginosa: effect of arsenite and other metabolic inhibitors; Banerjee PC; Biosynthesis of alginic acid in presence of metabolic inhibitors by resting cells of mucoid Pseudomonas aeruginosa was studied . Among the inhibitors tested, arsenite exhibited very interesting results, while the others showed no remarkable effect . Firstly, arsenite stopped alginate production from all the substrates during initial hours of incubation; secondly, degradation of newly synthesized alginates to smaller molecular weight fragments took place if it was added after a few hours of incubation with the substrate; and thirdly, uncontrolled synthesis of alginate started after several hours of inhibition . Presence of arsenite was needed for the initial inhibitory phase of alginate synthesis; but once the cells were capable of synthesizing alginate after initial hours of inhibition, arsenite may be omitted from the medium. Zh Mikrobiol Epidemiol Immunobiol, 1986 Sep, (9), 90 - 2 {Dynamics of the contamination of mice during the treatment of burn sepsis due to Pseudomonas aeruginosa using tobramycin alone or combined with active and passive immunization}; Minukhin VV et al.; An experimental study was made with a view to finding out the possible bacteriological advantages of the combined use of tobramycin (Tb) and P . aeruginosa corpuscular polyvalent vaccine (PaCPV) or P . aeruginosa hyperimmune plasma (PaHIP) in burn sepsis caused by P . aeruginosa . The use of the median therapeutic dose of Tb (2.5 mg/kg body weight per day), alone or in combination with immunopreparations, ensured the survival rate of the animals equal to 100% . The contamination of the body with P . aeruginosa after treatment with Tb and PaHIP or PaCPV was lower than after the administration of Tb alone, this phenomenon becoming manifest starting from day 5 of observation in the first case and from day 10 in the second case . The combined use of Tb and immunopreparations (PaCPV or PaHIP) in acute P . aeruginosa infection proved to be more effective than treatment with Tb alone. Can J Microbiol, 1986 Sep, 32(9), 751 - 5 {Bacterial interference with skin colonization in germfree hairless mice}; Barc MC et al.; Bacterial colonization of the digestive tract and the skin was studied over a 3-week period in a group of 10 germfree HRS mice using Staphylococcus epidermidis, Staphylococcus aureus, and Pseudomonas aeruginosa . Sequential utilization of two strains allowed us to carry out six assays and to show the presence of interference phenomena during colonization of the skin . When P . aeruginosa was given after challenge with S . aureus or S . epidermidis, it did not colonize the skin . If the first challenge was done with P . aeruginosa, this bacteria was eliminated within 10 days by S . aureus and S . epidermidis on the skin, but it succeeded in colonizing the digestive tract . When the first challenge was done with S . aureus, colonization of the skin and the digestive tract with S . epidermidis was prevented, whereas these two species were found in association when S . aureus was given in second place . None of the in vitro assays (mixed culture, bacteriocin production, adherence inhibition, antimicrobial activity) could explain the in vivo observations. Antimicrob Agents Chemother, 1986 Sep, 30(3), 453 - 7 Evidence for multiple forms of type I chromosomal beta-lactamase in Pseudomonas aeruginosa; Gates ML et al.; The multiple stages of derepression of the type I chromosomal beta-lactamase in Pseudomonas aeruginosa were examined . Mutants partially and fully derepressed for beta-lactamase were selected from a wild-type clinical isolate . An analysis of the beta-lactamase produced by these mutants and the induced wild type revealed significant differences in the products of derepression at each stage . Beta-lactamase produced by the fully derepressed mutant showed a lower affinity (Km, 0.113 mM) for cephalothin than that produced by the partially derepressed mutant (Km, 0.049 mM) . However, due to a very large Vmax, the former possessed a much greater hydrolytic efficiency . Differences in substrate profile were also noted . Only beta-lactamase from the fully derepressed mutant hydrolyzed cefamandole, cefoperazone, and cefonicid . The partially derepressed mutant possessed a single beta-lactamase band with a pI of 8.4 . The fully derepressed mutant possessed this band and an additional major band with a pI of 7.5 . Induction of the wild type with cefoxitin produced both bands . The changes in physiologic parameters of the enzymes produced in the different stages of derepression suggest a complex system for beta-lactamase expression in P . aeruginosa . This may involve at least two distinct structural regions, each of which is under control of the same repressor. Tohoku J Exp Med, 1986 Sep, 150(1), 69 - 75 Electron microscopic study of the cell surface of dibekacin-treated Pseudomonas aeruginosa; Aonuma S et al.; Electron microscopy of thin sections of Pseudomonas aeruginosa IAM 1007 treated with dibekacin revealed blebs, disintegration of the outer membrane of the cell wall and degenerative features of the cytoplasm . In the next experiment, the cell wall fraction was isolated from the mechanically disrupted cells, incubated with dibekacin and was subjected to electron microscopy, in order to find a clue to the action mechanism of dibekacin on the cell wall of Pseudomonas aeruginosa IAM 1007 . As a result, it was found that unidentified substances were released from the surface of the cell wall and that the outer membrane of the cell wall disappeared . The degree of changes of the cell wall ultrastructure was almost proportional to the length of incubation with dibekacin . These findings strongly suggest that dibekacin directly disintegrates the outer membrane of the cell wall of Pseudomonas aeruginosa IAM 1007. Mol Gen Genet, 1986 Sep, 204(3), 519 - 23 The Hfr status of Pseudomonas aeruginosa is stabilized by integrative suppression; Herrmann H et al.; A temperature-sensitive mutant (dna-11) with the phenotype of a mutant defective in the initiation of DNA replication, was isolated from an Hfr-like FP2 donor of Pseudomonas aeruginosa . Reversion of its temperature-sensitive character was achieved by integrative suppression rather than by backmutation or an additional suppressor mutation . The dna-11 mutant proved to be helpful in stabilizing the Hfr status of the original host. J Infect, 1986 Sep, 13(2), 125 - 31 Ceftazidime alone for treating Pseudomonas aeruginosa septicaemia in neutropenic patients; Verhagen C et al.; Twenty-nine patients with primary or secondary hypoplastic bone-marrow were treated successfully with ceftazidime alone for established septicaemia caused by Pseudomonas aeruginosa of which 38% strains were gentamicin-resistant . All the patients were neutropenic at the start of therapy; most were cured with microbiological confirmation before the bone marrow had regenerated . One patient died of cerebral haemorrhage due to profound thrombocytopenia without evidence of infection at autopsy . Significant toxicity was not observed . Ceftazidime alone is, therefore, a safe and effective treatment for infections caused by this organism even in the neutropenic patient. J Clin Microbiol, 1986 Sep, 24(3), 372 - 6 Antibiograms, serotypes, and plasmid profiles of Pseudomonas aeruginosa associated with corneal ulcers and contact lens wear; Mayo MS et al.; Pseudomonas aeruginosa was isolated from the corneal scrapings of 11 of 14 patients with gram-negative corneal ulcers and from salt tablet-prepared saline solutions from 6 of these patients wearing soft contact lenses . Comparison of physiological properties, antibiograms, serotypes, and plasmid profiles for five of the patients indicated that the isolates from the ulcer and the saline solution of a given patients were of the same strain . Improper hygienic practices of contact lens wearers appeared to be a major factor in the epidemiology of pseudomonad corneal ulcers. J Clin Microbiol, 1986 Sep, 24(3), 317 - 23 Variation and adaptation of Pseudomonas aeruginosa toxicity to HeLa cells and fibroblasts; Muller H et al.; The toxic components of supernatants from Pseudomonas aeruginosa cultures directed against HeLa cells and Staphylococcus aureus were evaluated with the aim of discovering interactions . Supernatants of eight different strains of P . aeruginosa were assayed for cytotoxic activity . All were active against HeLa cells; seven were toxic for S . aureus . On repeated suspension of P . aeruginosa in 0.9% sodium chloride solution, a shift from HeLa cell toxicity to staphylococcal lytic activity occurred along with a change of toxic activity from a high (50,000 +/- 5,000) to a low (8,000 +/- 400) molecular weight (MW) range on gel filtration . Addition of protein to the minimal medium of cultures producing material toxic only for S . aureus reactivated the generation of HeLa cell-toxic material . Cultivation of P . aeruginosa in the presence of HeLa cells and a chloramphenicol supplement produced suppression of the generation of material toxic for S . aureus but facilitated that of HeLa-toxic material of high MW . Adaptation of toxicity against fibroblasts developed only on cocultivation of P . aeruginosa together with S . aureus and in the presence of fibroblasts . Under these conditions a strong lytic activity for S . aureus appeared, even in the presence of chloramphenicol . Chloramphenicol caused the material toxic for fibroblasts to elute at a low MW well separated from that toxic for HeLa cells . In contrast to the high-MW toxic substances, the low-MW material did not induce antibodies after injection into rabbits . This may explain failures of vaccination against P . aeruginosa infection and of serum therapy of homologous sepsis in humans. Eur J Biochem, 1986 Sep 1, 159(2), 309 - 13 Purification and structural analysis of pyocyanin and 1-hydroxyphenazine; Watson D et al.; Pyocyanin and related members of the phenazine family are produced by Pseudomonas aeruginosa and have been associated with events of pathophysiological importance . Pyocyanin and its base hydrolysis product 1-hydroxyphenazine were purified to homogeneity by reverse-phase high-pressure liquid chromatography . Their mass spectrometric behaviour was examined with a view to evaluating the use of high-resolution chromatography/mass spectrometry in studying phenazine-mediated effects in man . The molecular mass of naturally derived pyocyanin was determined as 210 Da by thermospray liquid chromatography/mass spectrometry and confirmed by desorption electron-impact mass spectrometry . Mass spectrometric data could not be obtained by fast-atom bombardment or desorption chemical ionisation, techniques commonly used to determine molecular mass of polar or thermally labile species . The thermal lability of underivatised pyocyanin precluded analysis by gas chromatography/mass spectrometry . In contrast to pyocyanin, mass spectrometric data were readily obtained for 1-hydroxyphenazine, using direct probe analysis as well as with gas and liquid chromatography inlet systems. Infect Immun, 1986 Sep, 53(3), 621 - 7 Monoclonal antibodies to Pseudomonas aeruginosa ferripyochelin-binding protein; Sokol PA et al.; Hybridomas secreting specific monoclonal antibodies against the Pseudomonas aeruginosa ferripyochelin-binding protein (FBP) were isolated . These monoclonal antibodies reacted with FBP in immunoblots of outer membrane preparations from all serotypes of P . aeruginosa . Two of the monoclonal antibodies also reacted with FBP in strains of P . putida, P . fluorescens, and P . stutzeri . These antibodies did not react with outer membranes of P . cepacia, "P . multivorans," P . maltophilia, or other gram-negative organisms . The monoclonal antibodies were opsonophagocytic and blocked the binding of {59Fe}ferripyochelin to isolated outer membranes of strain PAO . By indirect immunofluorescence techniques, the monoclonal antibodies were used to demonstrate that FBP is present on the cell surface of P . aeruginosa cells grown in low-iron but not high-iron medium . These observations were confirmed by using 125I in surface-labeling techniques. Infect Immun, 1986 Sep, 53(3), 611 - 5 T-cell-independent macrophage activation in mice induced with rRNA from Listeria monocytogenes and dimethyldioctadecylammonium bromide; van den Bosch JF et al.; Purified rRNA from Listeria monocytogenes or Pseudomonas aeruginosa injected in combination with dimethyldioctadecylammonium bromide (DDA), protects mice nonspecifically against a lethal challenge of various extra- and intracellular bacteria . In the present study vaccination of BALB/c as well as C57BL/Ka mice with listerial RNA-DDA resulted in activation of fixed-tissue macrophages, as measured by an enhanced in vivo L . monocytogenes killing in spleen and liver . Evidence was found that macrophage activation by vaccination with rRNA-DDA occurred by a T-cell-independent mechanism . Treatment of mice with cyclosporin A had no effect on the enhanced L . monocytogenes killing induced with RNA-DDA; in vitro exposure of RNA-DDA to spleen cell cultures did not give rise to any lymphocyte proliferation . No evidence could be found for a possible adjuvant activity for RNA-DDA in cellular responses; in fact, RNA-DDA had an inhibitory effect on lymphocyte proliferative responses to Listeria antigen and to concanavalin A. Bioorg Khim, 1986 Sep, 12(9), 1268 - 73 {Antigenic polysaccharides of bacteria . 17 . The structure of O-specific polysaccharide chain of Pseudomonas aeruginosa X (Meitert) lipopolysaccharide}; Knirel' IU et al.; O-Specific polysaccharide composed of L-rhamnose and 2-acetamido-2-deoxy-D-mannose was obtained on mild acid degradation of P . aeruginosa X (Meitert classification) lipopolysaccharide . On the basis of non-destructive analis using 1H, 13C NMR spectroscopy and Klyne's rule calculation, as well as chemical methods (acid hydrolysis, methylation, Smith degradation), it was established that the polysaccharide is built up of disaccharide repeating units of the following structure: ----4)-alpha-L-Rha-(1----3)-beta-D-ManNAc-(1----. Bioorg Khim, 1986 Sep, 12(9), 1263 - 7 {Antigenic polysaccharides of bacteria . 16 . The structure of O-specific polysaccharide chain of Pseudomonas aeruginosa 025 (Wokatsch) lipopolysaccharide}; Knirel' IuA et al.; O-Specific polysaccharide built up of trisaccharide repeating units containing 3-acetamidino-2-acetamido-2,3-dideoxy-D-mannuronic acid (ManNAcAmA), 2,3-diacetamido-2,3-dideoxy-D-mannuronic acid (Man(NAc)2A), N-acetyl-D-fucosamine (FucNAc), and O-acetyl group was obtained on mild acid hydrolysis of P . aeruginosa O25 (Wokatsch classification) lipopolysaccharide . Basing on de-O-acetylation of polysaccharide with aqueous triethylamine accompanied by hydrolysis of acetamidino group to acetamido group, as well as on the 1H and 13C NMR data, the following structure of the repeating unit of the polysaccharide was established: (Formula: see text) P . aeruginosa O25 polysaccharide has the same carbohydrate skeleton as that of P . aeruginosa O3a,b (Lanyi classification) and differs from the latter only by the presence of the O-acetyl group at position 4 of N-acetylfucosamine. Infect Immun, 1986 Sep, 53(3), 656 - 62 Functionally active monoclonal antibody that recognizes an epitope on the O side chain of Pseudomonas aeruginosa immunotype-1 lipopolysaccharide; Stoll BJ et al.; A murine monoclonal antibody (MAb) was prepared against Pseudomonas aeruginosa immunotype-1 (It-1) lipopolysaccharide (LPS) . The MAb bound It-1 LPS in the enzyme-linked immunosorbent assay and in the immunodiffusion and immunoblotting assays, agglutinated and opsonized It-1 bacteria, and protected against challenge with live It-1 organisms in a murine burn infection model . All of these activities were immunotype specific . Correlation of the opsonic and protective properties of the MAb with its recognition site on the LPS O side chain confirmed that such immunotype-specific determinants are important targets for protective antibodies in Pseudomonas disease . The functional equivalence of this MAb and polyclonal antibodies from hyperimmune plasma underscores the therapeutic potential of single MAbs which recognize critical determinants in the LPS O side chain. J Biol Chem, 1986 Aug 25, 261(24), 11404 - 8 Pseudomonas exotoxin A . Membrane binding, insertion, and traversal; Farahbakhsh ZT et al.; Using vesicle targets composed of phosphatidylcholine and cholesterol (1:1 molar ratio), we found that Pseudomonas aeruginosa exotoxin A (PTx) binding and insertion are not only dependent on pH (Zalman, L.S., and Wisnieski, B.J . (1985) Infect . Immun . 50, 630-635) but also on ionic strength, reaching a maximum in pH 4 buffer that contains 150-200 mM NaCl . Insertion was monitored by photolabeling with an intramembranous probe . Higher levels of binding and insertion were attained with vesicles that contained 2.5 mol% dicetylphosphate than with neutral vesicles . Positively charged vesicles (2.7 mol% stearylamine) were the least effective targets . At pH 7.4, all binding levels were depressed . While PTx binding increased with increasing temperature, the relative proportion of the vesicle-associated toxin that was photolabeled decreased . The most likely explanation for the decrease is that the bilayer translocation rates increased with increasing temperature, and hence fewer PTx molecules were accessible at the time of photolabeling . At 37 degrees C, binding and insertion both plateaued within 10 min of lowering the pH to 4 . After 10 min, the amount of bound toxin decreased slightly with time but there was a dramatic decrease in photolabeling, indicating that inserted PTx had begun to cross the bilayer . This was verified by the finding that when PTx was incubated with vesicles that contained trypsin, cleavage occurred only in those samples in which the pH was shifted down to pH 4 . Entry is triggered by an acid-induced conformational change that promotes productive binding and insertion . After insertion, the kinetics of membrane traversal appear to be regulated by the physical properties of the bilayer. J Biol Chem, 1986 Aug 25, 261(24), 11259 - 65 Isolation and characterization of a lysine-specific protease from Pseudomonas aeruginosa; Elliott BW Jr et al.; We report here a procedure which results in the purification of an extracellular protease (designated Ps-1) from Pseudomonas aeruginosa . This enzyme cleaves fibrinogen so that the modified molecules form microcrystals and large single crystals . Precise knowledge of the Ps-1 cleavage sites is essential for the interpretation of the structural information provided by these crystals (Weisel, J . W., Stauffacher, C . V., Bullitt, E., and Cohen, C . (1985) Science 230, 1388-1391) . Ps-1 is a single-chain polypeptide of Mr 30,000 which appears to function as a monomer . The pH optimum is 8-9 . The activity of the protease is not decreased by inhibitors of thiol, carboxyl, or metallo proteases; the abolishment of activity by N alpha-p-tosyl-L-lysine chloromethyl ketone and the partial inhibition obtained with serine-reactive inhibitors suggests that Ps-1 may be a serine protease with an unusual active-site conformation . Studies with synthetic peptide substrates show that Ps-1 exhibits one of the most restricted specificities known for an endoproteinase: only peptide, ester, and amide bonds containing the carbonyl group of lysine are hydrolyzed . The limited specificity of Ps-1 should make it useful for other applications requiring the selective cleavage of proteins, such as sequence analysis and the isolation of domains. Biochim Biophys Acta, 1986 Aug 21, 860(2), 263 - 7 Role of lysines in ion selectivity of bacterial outer membrane porins; Hancock RE et al.; The epsilon-amino groups of available lysine residues of the OmpC, OmpF and PhoE porin proteins of Escherichia coli and of the protein P porin of Pseudomonas aeruginosa, were modified by the bulky reagent trinitrobenzenesulphonic acid . Approximately 78% of the lysines of the anion-selective protein P and PhoE porins were modified whereas only 40-50% of the lysines of the cation selective OmpF and OmpC porins were altered . After modification, the three E . coli porins had very similar high selectivities for cations over anions, in contrast to the native porins which varied 86-fold in ion selectivity . Despite the large size of the trinitrophenyl group attached to modified lysines (i.e., a disc of approx . 0.86 nm diameter X 0.36 nm high) relative to the reported size of the constrictions of the E . coli porins (1.0-1.2 nm diameter), only the anion-selective PhoE porin was substantially blocked after trinitrophenylation . The protein P porin channel was relatively unaffected by trinitrophenylation, in contrast to previous data showing dramatic effects of acetylation of lysines on protein P conductance and selectivity . This favoured a model in which the critical lysines involved in anion binding by protein P were present in a constriction of the channel that was too small for trinitrobenzenesulphonic acid to enter . Overall, the data suggest that both the number and relative position of charged lysines are major determinants of ion selectivity. J Antibiot (Tokyo), 1986 Aug, 39(8), 1092 - 107 Synthesis and structure-activity relationships of a new series of cephalosporins, BMY-28142 and related compounds; Naito T et al.; The synthesis of a series of 7-{(Z)-2-(2-aminothiazol-4-yl)-2-oxyiminoacetamido} -3-ammoniomethyl-3-cephems is described . Variations of an oxyimino moiety in the 7-side chain and a quaternary ammonium moiety in the 3-side chain were examined and structure-activity relationships studied . BMY-28142, the 3-(N-methylpyrrolidinio)methyl derivative of the 7-alpha-methoxyimino series of cephalosporins, exhibited broad antimicrobial activity against both Gram-positive and Gram-negative bacteria including Pseudomonas aeruginosa. Ophthalmic Surg, 1986 Aug, 17(8), 499 - 501 Eyelid necrosis in an anophthalmic patient; Woog JJ et al.; A 72-year-old woman with chronic lymphocytic leukemia developed periorbital swelling, erythema, and discharge involving her anophthalmic left socket in the course of pseudomonas aeruginosa septicemia . Histopathologic examination of debrided eyelid tissues revealed ischemic necrosis of the eyelid margin and deeper eyelid tissues . Underlying malignancy, disseminated systemic infection, and alteration in the vascular supply to the eyelids following enucleation may have contributed to the development of ischemic eyelid necrosis in this patient. Antimicrob Agents Chemother, 1986 Aug, 30(2), 260 - 6 Pharmacokinetics and pharmacodynamics of ciprofloxacin in cystic fibrosis patients; LeBel M et al.; The pharmacokinetics and blister fluid penetration of oral ciprofloxacin were compared in 11 cystic fibrosis (CF) patients who had sputum colonization but were asymptomatic and in 12 healthy volunteers after a single dose (500 mg) and at steady state (500 mg every 8 h) . The antibacterial effect of ciprofloxacin therapy was also evaluated by bacterial counts of colonizing pathogens in the respiratory secretions of CF patients . The CF patients were 15.9% lighter in weight than the controls (P less than 0.05) . After a single dose, the elimination half-life of ciprofloxacin was decreased by a third in the CF patients as compared with the controls (2.62 versus 3.93 h, respectively; P less than 0.01) . This was the result of a diminished apparent volume of distribution in CF subjects . Interestingly, we observed no statistically significant difference in total apparent and renal clearances between the groups . Suction-induced blister fluid penetration was not different between CF patients and healthy volunteers . In CF patients, ciprofloxacin exhibited levels in respiratory secretions above the reported MIC for Pseudomonas aeruginosa: 1.36 and 1.86 micrograms/ml at 2 h after a single dose and at steady state, respectively . An important fall (mean, 3.9 log10/ml) in the log titer in 10 patients with P . aeruginosa in their respiratory secretions was observed after 5 days of treatment . However, this improvement was short-lived; the secondary increase in bacterial counts observed in five patients and the development of five resistant strains were causes for concern . The pharmacokinetic results presented here showed that ciprofloxacin should be administered every 8 or even every 6 h in CF patients. Zh Mikrobiol Epidemiol Immunobiol, 1986 Aug, (8), 42 - 5 {Experimental basis for the combined use of tobramycin and immune preparations for treating acute Pseudomonas aeruginosa infections}; Minukhin VV et al.; The possibility of using tobramycin (Tb) in combination with P . aeruginosa polyvalent corpuscular vaccine (PaPCV) or pyocyanosis hyperimmune plasma (PHP) for the treatment of P . aeruginosa sepsis was experimentally studied . The combined use of Tb and PHP, administered in amounts corresponding to ED50 of each preparation used separately, ensured the survival of 90% of the infected mice, and the injected of PaPCV with ED50 of the antibiotic ensured the survival of 73% of the experimental animals . The combined use of Tb and the two immuno-preparations (PaPCV and PHP) for the treatment of P . aeruginosa infection proved to be more effective than their separate administrations. Zh Mikrobiol Epidemiol Immunobiol, 1986 Aug, (8), 18 - 21 {Tetrathionate reductase as a diagnostic trait in identifying Pseudomonas aeruginosa}; Kalina GP et al.; The tetrathionate reductase test may be used for the identification of P . aeruginosa . The most reliable results have been obtained with the use of a medium containing sodium tetrathionate for this purpose, and replacing bromthymol blue used as an indicator for phenol red excludes the possibility of false negative reactions. Am Rev Respir Dis, 1986 Aug, 134(2), 214 - 6 Lack of bacterial aerosols associated with heat and moisture exchangers; Saravolatz LD et al.; Contaminated condensate might serve as a source for cross infection . Heat and moisture exchangers (HME) are devices that humidify inspired gases, which pass through a hygroscopic felt pad surrounded by a cellulose sponge housed in a plastic case . In our study, we used a Servo 150 HME in place of a cascade humidifier in mechanical ventilator circuits . We performed 2 studies to evaluate the microbiologic safety of the HME . First, 42 HMEs used by patients for 24 h were tested in the laboratory for contamination . To simulate patient/air exchange, the HMEs were connected to the Andersen Sampler (flow at 35 L/min x 20 min) . Although the inner felt pad of the HMEs was contaminated in 74% of the units (31 of 42), only 4.8% (2 of 42) generated 1 to 2 bacteria/702 L of air . In a second study, HMEs contaminated with either Staphylococcus aureus or Pseudomonas aeruginosa (at 10(3), 10(5), or 10(8) organisms/ml) were connected to an Andersen Air Sampler to simulate a ventilator circuit . Bacterial aerosols were not generated, with the exception of 2 to 4 bacteria recovered after contamination with 10(8) bacteria . The HME can provide humidification for mechanically ventilated patients with little risk of generating respirable bacterial aerosols. J Infect Dis, 1986 Aug, 154(2), 289 - 94 Emergence of resistance to imipenem during therapy for Pseudomonas aeruginosa infections; Quinn JP et al.; We studied the mechanism of resistance to imipenem in three clinical isolates of Pseudomonas aeruginosa . Two of these isolates arose from imipenem-susceptible strains isolated during therapy with imipenem and were associated with treatment failure . One of these two strains had previously been broadly resistant to beta-lactams; the second acquired resistance to imipenem alone . One isolate of the third strain was resistant to imipenem but susceptible to other antipseudomonal beta-lactams . No isolate contained beta-lactamase activity capable of hydrolyzing imipenem at a detectable rate . Studies of the penicillin-binding proteins of all isolates revealed no differences in the number of proteins, molecular weight of, affinity for penicillin, or affinity for imipenem in any isolate . In each case the resistant isolate lacked one or more outer membrane proteins that were present in a susceptible isolate of the same strain . The observed alterations in outer membrane proteins may be associated with diminished permeability of the bacterial outer membrane to imipenem and may be the major factor responsible for resistance in these isolates. Genetika, 1986 Aug, 22(8), 2048 - 54 {Effective, plasmid RP4-dependent replication-transposition of DNA of the transposable phage D3112 of Pseudomonas aeruginosa in a heterologous Escherichia coli system}; Akhverdian VZ et al.; The processes of replication and transposition of Pseudomonas aeruginosa transposable phage D3112 in cells of Escherichia coli (D3112) and E . coli (RP4::D3112) were studied . D3112 genome is a "silent cassette" ("conex-phage"--conditionally expressible) in E . coli cells incubated at 42 degrees C . Two compulsory conditions for D3112 genome expression are incubation at 30 degrees C and the presence in cells of RP4 plasmid . Processes of replication and transposition in E . coli are coupled . RP4 plasmid stimulates D3112 DNA synthesis in E . coli at least by two order of magnitude . In correspondence with this observation is the fact that when Mg2+ is present in high concentration (0.1 M) in a cultural medium, the production of mature phage is enhanced by two order of magnitude in E . coli (RP4::D3112) or in E . coli (D3112, RP4) cells, and is approx . 10(-1)-10(-2) phage per cell . No influence of Mg on phage production is observed in E . coli (D3112) cells. J Clin Microbiol, 1986 Aug, 24(2), 210 - 3 Oral succession of gram-negative bacilli in myelosuppressed cancer patients; Minah GE et al.; Aerobic and facultative gram-negative bacilli (GNB) have been reported to increase on various body surfaces in the seriously ill and debilitated patient . This study examined quantitative aspects of GNB succession at five oral sites in cancer patients before and during myelosuppressive chemotherapy . GNB concentrations increased sharply during chemotherapy at 25 to 50% of the oral sites in both acute nonlymphocytic leukemia and small-cell lung carcinoma patients . Most sites did not exhibit shifts of GNB to levels higher than 0.1% of the cultivable flora . When shifts occurred, all sites sampled in the mouth were usually affected and GNB usually represented more than 10% of the cultivable flora . Low levels of indigenous microflora were observed in most sites exhibiting GNB shifts . None of the subjects harboring high levels of GNB developed the symptoms of acute infection which are commonly observed in myelosuppressed patients . Although Pseudomonas aeruginosa and Klebsiella pneumoniae were recovered from some sites, most GNB were nonpathogenic species of Pseudomonas; Pseudomonas pickettii was the most frequently recovered. J Bacteriol, 1986 Aug, 167(2), 473 - 9 Expression in Escherichia coli and function of Pseudomonas aeruginosa outer membrane porin protein F; Woodruff WA et al.; The gene encoding porin protein F of Pseudomonas aeruginosa was cloned onto a cosmid vector into Escherichia coli . Protein F was expressed as the predominant outer membrane protein in a porin-deficient E . coli background and was clearly visible on one-dimensional sodium dodecyl sulfate-polyacrylamide gels in a porin-sufficient background . The identity of the protein F from the E . coli clone and native P . aeruginosa protein F was demonstrated by their identical mobilities on sodium dodecyl sulfate-polyacrylamide gel electrophoretograms, 2-mercaptoethanol modifiabilities, and reactivities with monoclonal antibodies specific of two separate epitopes of protein F . In the course of gene subcloning, a 2-kilobase DNA fragment was isolated, with an apparent truncation of the part of the gene encoding the carboxy terminus of protein F . This subclone produced a 24,000-molecular-weight, outer membrane-associated, truncated protein F derivative which was not 2-mercaptoethanol modifiable and which reacted with only one of the two classes of protein F-specific monoclonal antibodies . The 2-kilobase fragment was used in Southern blot hybridizations to construct a restriction map of the cloned and subcloned fragments and to demonstrate with restriction digests of whole P . aeruginosa DNA that only one copy of the protein F gene was present in the P . aeruginosa chromosome . The protein F produced by the original cosmid clone in a porin-deficient E . coli background was purified . To demonstrate retention of porin function after cloning, the protein F from the E . coli clone was incorporated into black lipid bilayer membranes . Two major classes of channels were revealed . The predominant class of channels had an average conductance of 0.36 nS in 1 M KCl, whereas larger channels (4 to 7 nS) were seen at a lower frequency . Similar channel sizes were observed for porin protein F purified by the same method from P . aeruginosa outer membranes. Endocrinology, 1986 Aug, 119(2), 515 - 21 Effects of an acute bacterial infection on serum thyroid hormones and nuclear triiodothyronine receptors in mice; Burgi U et al.; Serum T3, T4, and rT3 levels as well as liver nuclear T3 receptors (NT3R) were measured in mice with a bacterial infection . Pseudomonas aeruginosa were injected into one thigh of ICR mice, resulting in a severe infection at sacrifice 15 h later . Since food intake, which influences serum thyroid hormone levels and NT3R, was 75% lower in infected than in control mice, infected mice were either fed and compared with pair-fed controls or fasted and compared with fasted and fed controls . Fasting induced a fall in serum T3 and T4 levels, which was even more pronounced in infected fasted animals . However, while fasting caused an approximately 80% increase in serum rT3 concentrations, serum rT3 levels in infected fasted animals were not different from those in fed controls . The combination of infection and fasting thus prevented the rise in serum rT3 otherwise invariably associated with fasting . NT3R measurements on isolated nuclei revealed the presence of NT3R in mouse liver similar to those reported in rat liver . The NT3R Kd (approximately 2 X 10(-10) M) was not affected by decreased food intake, infection, or a combination thereof . The NT3R maximum binding capacity (MBC) was decreased in fasted animals (460 vs . 306 pg/mg DNA) . However, the MBC of infected fasted mice was not different from that of fasted mice . Similarly, no difference in MBC was found between infected fed and pair-fed control mice . In mice injected with heat-killed P . aeruginosa to evaluate potential effects of endotoxins, neither serum thyroid hormone levels nor hepatic NT3R were different from those of controls . These data show that in mice, a severe bacterial infection with P . aeruginosa has effects on serum hormone levels not explained by the disease-associated diminished food intake, whereas it has no effects on liver NT3R beyond those due to the disease-related decreased food intake. Acta Pathol Microbiol Immunol Scand {B}, 1986 Aug, 94(4), 273 - 6 Population analyses of the susceptibility to ciprofloxacin of eight clinical strains of Pseudomonas aeruginosa; Gerner-Smidt P et al.; Population analyses of the susceptibility to ciprofloxacin of eight strains of Pseudomonas aeruginosa, including mucoid strains and strains resistant to aminoglycosides or anti-Pseudomonas beta-lactams, were carried out . All strains were sensitive as judged by the broth-dilution technique, but four strains were found to yield resistant mutants with a frequency of less than 10(-6) . Two strains yielded mutants homogeneously sensitive to ciprofloxacin at a level 8-16 times the MIC of the parent strains . Two other strains yielded mutants resistant to different higher concentrations of ciprofloxacin . One of these mutants was examined for production of ciprofloxacin-inactivating enzyme; no enzyme production could be detected . Cross-resistance was found with another quinolone antibiotic, ofloxacin, but not with aminoglycosides or beta-lactam antibiotics. J Clin Microbiol, 1986 Aug, 24(2), 189 - 96 Polysaccharide surface antigens expressed by nonmucoid isolates of Pseudomonas aeruginosa from cystic fibrosis patients; Pier GB et al.; We tested nonmucoid Pseudomonas aeruginosa isolates obtained from cystic fibrosis (CF) patients for the expression of lipopolysaccharide (LPS) serotype antigens, serum sensitivity, and production of mucoid exopolysaccharide (MEP) . When all nonmucoid isolates were compared with a set of random mucoid isolates, 20 of 52 (38%) nonmucoid isolates were typable and serum resistant, compared with 13 of 51 (24%) mucoid isolates (P = 0.16 by chi-square analysis) . However, nonmucoid strains from CF patients colonized only with nonmucoid strains were more frequently typable and serum resistant (67%) than were nonmucoid isolates from patients cocolonized with mucoid strains (31%) (P = 0.012, Fisher exact test) . An inhibition enzyme-linked immunosorbent assay done with bacterial extracts, a direct-whole-cell enzyme-linked immunosorbent assay done with affinity-purified antibody to MEP, and immune electron microscopy all demonstrated production of MEP by all nonmucoid P . aeruginosa isolates tested, including nonmucoid revertants of mucoid strains . No other bacterial species tested positive in these assays . These findings suggest that MEP is produced by all P . aeruginosa isolates obtained from CF patients, that the initial colonizing nonmucoid strains produce a smooth LPS, and that once LPS-rough, mucoid strains appear in the sputum, the predominant LPS phenotype is rough regardless of colony morphology. J Clin Invest, 1986 Aug, 78(2), 375 - 80 T lymphocyte-mediated protection against Pseudomonas aeruginosa infection in granulocytopenic mice; Powderly WG et al.; BALB/c mice immunized with Pseudomonas aeruginosa immunotype 1 polysaccharide develop protective T cell immunity to bacterial challenge . In vitro, T cells from immunized mice kill P . aeruginosa by production of a bactericidal lymphokine . The present study demonstrates that adoptive transfer of T cells from immunized BALB/c mice to granulocytopenic mice resulted in 97% survival on challenge with P . aeruginosa, compared with 17% survival with adoptive transfer of T cells from nonimmune BALB/c mice . This protection is specifically elicited by reexposure to the original immunizing antigen; adoptive recipients cannot withstand challenge with immunotype 3 P . aeruginosa . However, the adoptive recipients do survive simultaneous infection with both P . aeruginosa immunotypes 1 and 3 . Adoptive transfer of T cells from the congenic CB.20 mice, which are unable to kill P . aeruginosa in vitro, provides only 20% protection to granulocytopenic mice . These studies indicate that transfer of specific immune T lymphocytes can significantly enhance the resistance to P . aeruginosa infection in granulocytopenic mice. J Bacteriol, 1986 Aug, 167(2), 611 - 5 Overproduction and assay of Pseudomonas aeruginosa phosphomannose isomerase; Gill JF et al.; Phosphomannose isomerase activity was undetectable in extracts of mucoid (alginate-producing) Pseudomonas aeruginosa . When a P . aeruginosa gene previously shown to complement an alginate-negative mutant was overexpressed under the control of the tac promoter in the broad-host-range controlled-expression vector pMMB22, phosphomannose isomerase activity could be measured in extracts of P . aeruginosa and in a manA (phosphomannose isomerase-negative) mutant of Escherichia coli . P . aeruginosa extracts containing induced levels of enzyme were shown to interconvert fructose 6-phosphate and mannose 6-phosphate . A 56,000-dalton polypeptide was visualized on sodium dodecyl sulfate-polyacrylamide gels after induction in both hosts . When RNA-DNA dot- blot hybridization analysis was used, transcription of algA, the gene coding for P . aeruginosa phosphomannose isomerase, was not measurable from the chromosomes of either mucoid or nonmucoid P . aeruginosa . However, a high level of algA transcription was detected after expression of algA under tac promoter control in pMMB22. J Immunol, 1986 Aug 1, 137(3), 988 - 94 Antigenic specificities of Pseudomonas aeruginosa alkaline protease and elastase defined by human T cell clones; Parmely MJ et al.; Virulent strains of Pseudomonas aeruginosa derive their pathogenicity, in part, from their secretion of two proteolytic enzymes, alkaline protease (AP) and elastase (E) . Human T lymphocytes specific for AP and E can be detected in the blood of immune donors and have afforded the opportunity to characterize the antigenicity of these proteins . To accomplish this goal, we have recently selected 68 human T cell clones from five different Pseudomonas-immune donors and determined their fine specificities . Fifty-five (81%) were found to be protease specific, demonstrating the immunogenicity of the exoenzymes in humans . These clones defined five AP and three E specificities and suggested the existence of at least five allomorphic determinants expressed on the proteases of various Pseudomonas strains . Limiting dilution analysis confirmed a number of antigenic relationships suggested by the long-term T cell clones and revealed that T cells specific for allomorphic protease determinants were at least as frequent in the blood of immune donors as were T cells committed to conserved determinants . Thus, both primary and long-term human T cell clones showed specificity patterns that distinguished proteases from different Pseudomonas strains . These observations describe a heretofore unknown antigenic system of Pseudomonas aeruginosa that should assist in defining the nature and specificity of Pseudomonas immunity in humans. Am J Med, 1986 Jul 28, 81(1A), 73 - 7 Infection in patients with cystic fibrosis; Rubio TT; Cystic fibrosis is the most common lethal genetic disease of Caucasians . The disease affects the exocrine gland secretions throughout the body, and as a result, major pathologic changes develop in the pancreas and in the bronchi . Obstruction of the respiratory airways results in chronic infection, and in time, this leads to progressive deterioration of lung function . In the initial stages of the disease, usually during infancy, infection with Staphylococcus aureus plays an important role . Hemophilus influenzae infections are also common . As the disease progresses, infection with Pseudomonas aeruginosa develops . Exacerbation of bronchopulmonary infection is often initiated by respiratory viral or mycoplasmal infection, with superimposed S . aureus and P . aeruginosa infections contributing to the severity of the infection . Frequent courses of antibiotic therapy are usually required, and some patients may have to receive antibiotics continuously . Oral cephalosporins, ampicillin, and the combination of trimethoprim/sulfamethoxazole are commonly used for relatively mild infections . In the treatment of exacerbation of infection, intravenous penicillinase-resistant penicillins and anti-Pseudomonas antibiotics are the drugs of choice . For Pseudomonas infections, ticarcillin, carbenicillin, the ureidopenicillins, and the aminoglycosides are indicated . The combination of an anti-Pseudomonas penicillin and an aminoglycoside are most commonly used . Of the third-generation cephalosporins, ceftazidime appears to be the most efficacious . The quinolones (such as ciprofloxacin) are also active against P . aeruginosa, and preliminary studies of these drugs in patients with cystic fibrosis appear to indicate that they are as efficacious as the already available antibiotics . In many centers, Pseudomonas cepacia has emerged as a serious problem in patients with cystic fibrosis . This organism tends to develop resistance to multiple antibiotics . In some centers, infection with P . cepacia has been associated with a severe, frequently fatal, pneumonia. FEBS Lett, 1986 Jul 28, 203(2), 131 - 4 A copper-containing protein that inhibits nitrite reductase from Pseudomonas aeruginosa; Karapetian AV et al.; A non-blue copper-containing glycoprotein was isolated from Pseudomonas aeruginosa . The protein has a molecular mass of 10 kDa and contains 1 atom of EPR-detectable type II copper . The protein inhibits oxidation of both azurin and cytochrome c-551 catalyzed by nitrite reductase from Ps . aeruginosa . Thus, it may be considered as an endogenous inhibitor of nitrite reductase. Am Rev Respir Dis, 1986 Jul, 134(1), 22 - 6 Bacterial infection and acute lung injury in hamsters; Seidenfeld JJ et al.; Bacterial pneumonia is a common complication of lung injury that can be an important determinant of outcome . We studied experimental lung injury produced in hamsters by injecting 20 mg/kg paraquat (PQ) intraperitoneally; control animals received saline vehicle . Three days later, Pseudomonas aeruginosa (PAO1), 10(8) organisms in 0.25 ml, or saline, 0.25 ml, was inoculated intratracheally . Lung and systemic antibacterial defenses were studied at death 24 h later . Paraquat alone produced focal interstitial pneumonitis and neutrophilic alveolitis, and r