Eur J Clin Microbiol Infect Dis, 1992 Sep, 11(9), 782 - 8 Patterns of multiple resistance to antibiotics in gram-negative bacteria demonstrated by factor analysis; Leibovici L et al.; Principal component analysis was used to demonstrate the main associations between patterns of resistance to antibiotic drugs in 670 gram-negative bacteria consecutively isolated from blood cultures over a period of two years . Six factors were derived, which accounted for 84% of the total variance of the original matrix . Each factor represented an association between resistance to certain antibiotics as follows: factor 1: aztreonam, third generation cephalosporins and aminoglycosides; factor 2: first and second generation cephalosporins; factor 3: tetracycline and chloramphenicol; factor 4: ampicillin and ureidopenicillins; factor 5: trimethoprim/sulfamethoxazole; factor 6: fluoroquinolones . On two-way analysis of variance the difference in the factor scores was significant between bacteria for all factors except factor 5 . The difference in factor scores between community and hospital acquired strains was significant only for factors 1, 2 and 6 . Only the score of factor 6 showed a clear trend to increase with time during the two-year study period . Patients who were treated with antibiotics prior to bacteremia had higher scores for all factors, the difference being most marked in patients treated with fluoroquinolones . Factor analysis can be used to describe phenotypic associations between resistance to antibiotics, and the factor score used to compare groups of isolates and to demonstrate temporal and other trends. Clin Investig, 1992 Sep, 70(9), 825 - 42 The inflammatory function of renal glomerular mesangial cells and their interaction with the cellular immune system; Radeke HH et al.; The autoimmune nature of chronic progredient glomerular diseases has been well established . Like in other chronic inflammatory diseases, the active role of organ-borne cells has become increasingly apparent--both for the inflammatory process and for the initiation and perpetuation of the immune reaction . In most forms of glomerulonephritis, intrinsic glomerular mesangial cells are likely candidates to come into intimate contact with immune cells such as monocytes or lymphocytes . On the basis of cell culture studies we would like to integrate the current knowledge available about the responsiveness of mesangial cells to inflammatory agents and the resulting secretory capacity and, moreover, their possible role in sustaining chronic inflammatory injury and autoimmune reactions through a direct interaction with lymphocytes . Apart from being responsive to physiological stimuli such as angiotensin II, glomerular mesangial cells are predominantly activated by agents related to inflammation . This includes exogenous substances such as the components of gram-negative bacteria and an array of highly potent immunological stimuli like antigen-antibody complexes, activated complement, or various cytokines . The transformation of resting mesangial cells to proliferating cells with an accompanying expansion of their secretory profile and responsiveness is due to mediators like platelet-derived growth factor, transforming growth factor, and others . Numerous low-molecular-weight substances (O2-, H2O2, NO, platelet-activating factor, eicosanoids), proteins (proteinases, matrix components, interleukins 1 and 6, colony-stimulating factors, growth factors), and cell-surface molecules released or expressed by mesangial cells participate in the inflammatory process . Among these products interleukin 1 and/or 6, class II major histocompatibility antigen and integrins also support an interaction with the cellular immune system . It has been well documented that mesangial cells induced in vitro by recombinant T-cell lymphokines, such as interferon-gamma, do express MHC II and ICAM-1 and could function as antigen-presenting cells . However, and perhaps more interestingly, our own recent experiments with cocultures of syngeneic mouse lymphocytes and mesangial cells have demonstrated that T-cells are directly activated by cultured mesangial cells, thus resembling a mesangial cell-specific autoimmune reaction . In parallel to clinical studies searching for a mesangial autoantigen these experiments might help to elucidate the mechanisms of initiation and perpetuation of mesangial cell-dependent autoimmune glomerulonephritis. Z Naturforsch {C}, 1992 Sep-Oct, 47(9-10), 757 - 61 Electrostatic potential barrier in asymmetric planar lipopolysaccharide/phospholipid bilayers probed with the valinomycin-K+ complex; Seydel U et al.; Using the carrier-ion complex valinomycin-K+, current/voltage (I/U) characteristics were registered for planar asymmetric lipid bilayers composed on one side of a phospholipid mixture and on the other side of rough mutant lipopolysaccharide . This system resembles the lipid matrix of the outer membrane of Gram-negative bacteria . The evaluation of the current/voltage curves yielded a highly asymmetric electrical potential barrier . The total potential difference between the phospholipid and the lipopolysaccharide was -85 mV, a result which cannot be explained by contributions of Gouy-Chapman potentials alone . The possible contribution of dipole potentials and influences of headgroup effects are discussed . It is shown that the asymmetry of the I/U-characteristic results from the differences of the surface charge densities of the two monolayers but not from those of the states of order of their hydrocarbon chains. FEMS Microbiol Immunol, 1992 Sep, 5(1-3), 37 - 43 Activation of Escherichia coli prohemolysin to the membrane-targetted toxin by HlyC-directed ACP-dependent fatty acylation; Hughes C et al.; Hemolysin (HlyA) and related toxins of Escherichia coli and other Gram-negative pathogenic bacteria form membrane pores in cells of the host immune system, causing cell dysfunction and death . An insight into the mechanism by which HlyA is targetted to mammalian cell membranes was achieved by establishing in vitro activation of the non-toxic precursor proHlyA . By this approach we have discovered that conversion of proHlyA to the post-translational active HlyA toxin is determined by fatty acylation of proHlyA in an apparently novel process directed by the HlyC homodimer activator protein, and dependent upon the cellular acyl carrier protein (ACP) . By further exploiting the in vitro activation system it is now possible to obtain direct evidence that HlyC binds to an internal recognition sequence in the proHlyA precursor, in this way providing specificity for the transfer to proHlyA of a fatty acid moiety carried by the ACP . It is possible that the fatty acid modification determines directly the binding of HlyA to mammalian membrane lipids, thus initiating the toxin interaction with the target cells. Antimicrob Agents Chemother, 1992 Sep, 36(9), 1971 - 7 Studies of the effect of a platelet-activating factor antagonist, CL 184,005, in animal models of gram-negative bacterial sepsis; Torley LW et al.; The effect of CL 184,005, a potent and specific platelet-activating factor antagonist, has been examined in a variety of animal models relevant to gram-negative bacterial sepsis . Pretreatment of mice with CL 184,005 protected them from the lethal effects of platelet-activating factor . When rats or primates rendered hypotensive with endotoxin were treated with CL 184,005, blood pressure was normalized . Pretreatment of rats with CL 184,005 protected them from the gastrointestinal lesions induced by endotoxin . Pretreatment of rats and mice with CL 184,005 protected them from the lethal effects of endotoxin . Plasma tumor necrosis factor levels in endotoxin-treated mice were lower when the mice were pretreated with CL 184,005 . These observations suggest that CL 184,005 may be potentially useful in the treatment of gram-negative bacterial sepsis, and the agent is undergoing clinical evaluation. Int J Hyperthermia, 1992 Sep-Oct, 8(5), 689 - 99 Lethal interaction between heat and methylene blue in Escherichia coli; Menezes S et al.; Hyperthermia treatment is shown to act synergistically with methylene blue (MB), from the end point of lethality in Gram-negative Escherichia coli bacteria . That this lethality is correlated to the damage produced in DNA by the dye is deduced from the fact that bacteria differing in capacity for repair are almost equally sensitive to heat, but differ considerably in sensitivity to concomitant heat and dye treatment . It is demonstrated that the damage is repairable by the excision-repair system . The role of temperature seems to be that of facilitating the incorporation of the dye, which enables the latter to intercalate into the DNA . Ability of the outer membrane of E . coli AB1157 bacteria to act as a barrier to the penetration of MB remains almost intact up to 46 degrees C, but above this temperature it seems to disrupt abruptly (but reversibly), leading to inactivation of the cells by the dye . Since hyperthermia is in current use for the treatment of cancer, it is suggested that if this synergism also exists in mammalian cells, MB could eventually be used independently of its photodynamic action as an adjuvant in cancer therapy. J Clin Microbiol, 1992 Sep, 30(9), 2506 - 8 Osteomyelitis and intervertebral discitis caused by Pseudomonas pickettii; Wertheim WA et al.; Pseudomonas pickettii, a nonfermenting, gram-negative rod, is rarely pathogenic . Previous reports of infection with P . pickettii have largely involved direct contamination of supplies presumed to be sterile . We describe a case of vertebral osteomyelitis and intervertebral discitis caused by P . pickettii in a debilitated patient . The aggressive nature of this infection demonstrates that P . pickettii may be a more invasive organism than previously noted, particularly in hosts with weakened immunity secondary to underlying disease. J Appl Physiol, 1992 Sep, 73(3), 925 - 31 Effects of ibuprofen and pentoxifylline on the cardiovascular response of normal humans to endotoxin; Martich GD et al.; Endotoxin is a major mediator of the life-threatening cardiovascular dysfunction that characterizes Gram-negative sepsis . In animal models of endotoxemia, pretreatment with ibuprofen or pentoxifylline attenuates some of these cardiovascular changes . To evaluate the effects of these agents on the human cardiovascular response to endotoxemia, hemodynamic variables were measured serially in 24 normal subjects who were given intravenous endotoxin . The subjects were randomized to receive oral ibuprofen (n = 9), pentoxifylline (n = 10), or no medication before endotoxin administration (n = 5) . The subjects were volume loaded 3-5 h after endotoxin administration, and hemodynamic measurements were reassessed . Core temperature after endotoxin alone or endotoxin-pentoxifylline approached a maximum at 3 h (greater than or equal to 38.6 degrees C), while the endotoxin-ibuprofen group remained afebrile . At 3 and 5 h, all three groups had significant increases in heart rate, cardiac index, oxygen delivery, and oxygen consumption, while systemic vascular resistance index decreased significantly from baseline . The oxygen extraction ratio remained unchanged . After volume loading, the left ventricular ejection fraction and left ventricular end-diastolic and end-systolic volume indexes did not differ among the groups . The hyperdynamic cardiovascular response to endotoxin in humans occurs in the absence of fever and is not significantly ameliorated by oral cyclooxygenase or phosphodiesterase inhibition. Int J STD AIDS, 1992 Sep-Oct, 3(5), 355 - 9 Chlamydia trachomatis antigen detection by Chlamydiazyme combined with Chlamydia Blocking Reagent verification; Zeeberg B et al.; Several options exist for the detection of chlamydial infection in a routine laboratory setting . Enzyme immuno assay (EIA) technology offers rapid turn around of results and is less technically demanding than chlamydial cell culture . In addition, recently introduced EIA confirmatory reagents have the potential to improve the accuracy of EIA detection . We have evaluated one such confirmatory reagent (Chlamydia Blocking Reagent, Abbott Laboratories) to determine the accuracy of the Chlamydiazyme EIA with special regard to interpretation of low absorbance values . An initial series of 192 male urethral specimens showed that use of a lowered cut off level (absorbance value 0.05) compared with that recommended by the manufacturer increased sensitivity of the EIA from 0.73 to 0.83, thus motivating studies on this interpretative modification . Of 1101 EIA reactive specimens, 65% were determined to be chlamydia positive by the Chlamydia Blocking Reagent . The proportion of female cervical specimens that did not confirm positive was elevated compared with male urethral specimens, 43% vs . 5.7% respectively . In samples yielding absorbance from the recommended cut off level to 0.05 (approximately 50% below), the corresponding figures were 78% and 14% respectively . In 85 selected EIA reactive samples, examination by a direct immunofluorescence staining assay (DFA) (MicroTrak, Syva Inc.) revealed elementary bodies in 85% of 67 blocking test positive and in 24% of 18 blocking test negative samples . The possibility that Gram-negative bacteria were responsible for unconfirmed EIA reactive specimens was investigated using bacterial suspensions . While EIA reactivity was noted with several strains for Gram-negative bacteria, both the blocking reagent and DFA correctly verified the absence of chlamydial antigen.(ABSTRACT TRUNCATED AT 250 WORDS) Cesk Epidemiol Mikrobiol Imunol, 1992 Sep, 42(3), 120 - 5 {A program for prevention of pseudomonas infections and immunoprophylaxis with PSAEVA vaccine}; Kahlich R et al.; The authors present three main trends of prevention of Gram-negative opportunistic infections investigated at the Cardiosurgical Clinic of the Institute of Clinical and Experimental Medicine . An important part is played by active and systematic surveillance with early signalling and analysis of new infections with subsequent aimed interventions against concrete sources of infection and mechanisms of transmission . It is necessary to think more of activation of endogenous infection the specific features of which make repression difficult and motivate investigations of preventive approaches . Rational antibiotic policy has so far not appreciated the danger of selection of endogenous and exogenous agents in standard situations where antibiotic therapy lacks an aimed and restrained approach . Immunoprophylaxis with the PSAEVA vaccine in the first preliminary controlled clinical investigation was characterized by the absence of nosocomial epidemics and septicaemia and a significant (fivefold) reduction of the incidence of non-pyocyanic Gram-negative bacteriaemia . The success of vaccination seems to be related to the anti-colonization and anti-invasive mechanism of specific and unspecific nature. Cesk Epidemiol Mikrobiol Imunol, 1992 Sep, 42(3), 102 - 5 {New findings in emergency care and resuscitation in patients at risk for endotoxic shock}; Drabkova J; Endotoxin shock is not only the reflexion of Gram-negative focal infection but also the consequence of dysfunction of the intestinal mucous barrier and a decline of the detoxication capacity, in particular of the hepatic mesenchymal phagocytic system during a critical state . Cytokines and the primary LPS complex and its lipid A resp . are of basic importance . They start the release of a large amount of TNF alpha, IL-1, IL-6, IL-8 and other cascades . Acute shock is controlled nowadays more frequently than in the past, however, there is a high risk of a very adverse reaction of remote organs, which is very adverse from the prognostic aspect . A series of laboratory markers has a greater validity than the clinical picture alone . For screening derived markers are used not primary markers . Despite this they provide adequate information . Prophylaxis and treatment include selective bacterial decontamination, or active or passive immunization (PSAEVA, hyperimmune sera), minidoses of dopamine in a continuous infusion, early enteral nutritional intervention, in particular enteral nutrition containing glutamine . Monoclonal and polyclonal antibodies against the LPS complex and cytokines are tested, blocking their receptors or possibly early plasmapheresis . Permanent pillars of therapeutic tactics are still a radical and early elimination of possible infectious foci and targeted administration of antibiotics and maintenance of the perfusion pressure and adequate oxygenation. Ann R Coll Surg Engl, 1992 Sep, 74(5), 329 - 34 Prevention of bacterial infection and sepsis in acute severe pancreatitis; McClelland P et al.; Between 1984 and 1986 six patients with acute respiratory failure (requiring ventilation for at least 3 days) complicating acute pancreatitis were managed on the intensive care unit (median ventilation period 6 days; range 3-41 days) . Between 1987 and 1989 nine similar patients were managed (median ventilation period 35 days, range 4-69 days), and a regimen of enteral tobramycin, polymyxin and amphotericin to selectively decontaminate the digestive tract (SDD) was introduced . Five of six patients treated before 1987 had serious infections (three Gram-negative, one fungal), compared with only one of nine patients treated with SDD (P < 0.05) . Clinical signs of sepsis were evident for 62% of the pre-SDD period, compared with 39% of the period during SDD therapy (P < 0.001) . Systemic antibiotic prescribing was reduced in the SDD group; however, mortality remained unaffected with only two patients surviving pre-SDD and three during SDD treatment . SDD reduces infection rates and sepsis in patients with acute pancreatitis and may help to improve the prognosis of this life-threatening condition. Ugeskr Laeger, 1992 Aug 31, 154(36), 2437 - 8 {Meningitis caused by Capnocytophaga carnimorsus with development of erythema nodosum}; Storgaard M; A case of meningitis in a 42-year-old previously healthy man caused by the gram-negative rod Capnocytophaga carnimorsus is presented . The patient had erythema nodosum . Bacteremia was possibly induced during dental treatment. Nature, 1992 Aug 27, 358(6389), 727 - 33 Crystal structures explain functional properties of two E . coli porins; Cowan SW et al.; Porins form aqueous channels that aid the diffusion of small hydrophilic molecules across the outer membrane of Gram-negative bacteria . The crystal structures of matrix porin and phosphoporin both reveal trimers of identical subunits, each subunit consisting of a 16-stranded anti-parallel beta-barrel containing a pore . A long loop inside the barrel contributes to a constriction of the channel where the charge distribution affects ion selectivity . The structures explain at the molecular level functional characteristics and their alterations by known mutations. J Bacteriol, 1992 Aug, 174(16), 5450 - 3 Identification of a putative eukaryotic-like protein kinase family in the developmental bacterium Myxococcus xanthus; Zhang W et al.; Myxococcus xanthus is a gram-negative bacterium which, upon starvation, undergoes a spectacular developmental cycle culminating in the formation of spore-filled fruiting bodies . We recently characterized a protein serine-threonine kinase (Pkn1) that is required for normal development (J . Munoz-Dorado, S . Inouye, and M . Inouye, Cell 67:995-1006, 1991) . pkn1 was cloned by polymerase chain reaction amplification with primers designed from conserved sequences in eukaryotic protein kinases . In this study, a fragment of the pkn1 gene and an oligonucleotide corresponding to another highly conserved region were employed as probes for Southern blot analyses, which indicated that there are at least 26 putative kinase genes in M . xanthus . Most of the putative kinase genes were cloned, and complete or partial sequencing of eight clones revealed that they indeed contained highly conserved sequences present in eukaryotic kinases . These results suggest that complex kinase cascades similar to those described for eukaryotes might be involved in regulation of the M . xanthus life cycle. J Bacteriol, 1992 Aug, 174(16), 5237 - 43 Identification of amino acid substitutions that alter the substrate specificity of TEM-1 beta-lactamase; Palzkill T et al.; TEM-1 beta-lactamase is the most prevalent plasmid-mediated beta-lactamase in gram-negative bacteria . Recently, TEM beta-lactamase variants with amino acid substitutions in the active-site pocket of the enzyme have been identified in natural isolates with increased resistance to extended-spectrum cephalosporins . To identify other amino acid substitutions that alter the activity of TEM-1 towards extended-spectrum cephalosporins, we probed regions around the active-site pocket by random-replacement mutagenesis . This mutagenesis technique involves randomizing the DNA sequence of three to six codons in the blaTEM-1 gene to form a library containing all or nearly all of the possible substitutions for the region randomized . In total, 20 different residue positions that had been randomized were screened for amino acid substitutions that increased enzyme activity towards the extended-spectrum cephalosporin cefotaxime . Substitutions at positions 104, 168, and 238 in the TEM-1 beta-lactamase that resulted in increased enzyme activity towards extended-spectrum cephalosporins were found . In addition, small deletions in the loop containing residues 166 to 170 drastically altered the substrate specificity of the enzyme by increasing activity towards extended-spectrum cephalosporins while virtually eliminating activity towards ampicillin. Chest, 1992 Aug, 102(2), 613 - 7 Potential treatment of sepsis syndrome with cytokine-specific agents; Christman JW; Blocking the effects of cytokines is a potential new therapeutic avenue for the treatment of Gram-negative sepsis . Three classes of agents are currently being evaluated: antibodies, circulating inhibitors, and receptor antagonists . Data in the current literature support the consideration of these agents as potential therapeutic agents in Gram-negative sepsis . The clinical utility of these agents is contingent on the results of well-designed, prospective, randomized, placebo-controlled clinical trials in well-defined clinical populations . These trials will require the cooperation of clinical and basic scientists . At this time, preliminary and early clinical trials are in progress utilizing IL-1 and TNF-alpha circulating inhibitors, IL-1 receptor antagonists, and monoclonal antibodies to TNF-alpha and the TNF-alpha receptor. J Infect Dis, 1992 Aug, 166(2), 331 - 5 Role of interferon-gamma in experimental gram-negative sepsis; Silva AT et al.; To study the role of interferon-gamma (IFN-gamma) in gram-negative shock, mortality was compared in mice receiving either a monoclonal antibody to IFN-gamma (H22) or an irrelevant monoclonal antibody (L2-3D9) before or after an LD90 dose of Escherichia coli O111:B4 . H22 given either 1 h before or 0.5 h after bacterial challenge protected mice from death (mortality at 48 h, 28% vs . 83%, P less than .001) . Serum tumor necrosis factor-alpha (TNF alpha) levels and bacterial counts in blood and organs (liver, spleen, heart, and brain) were similar in H22-treated animals and controls . The peak serum TNF alpha levels were 95.7 +/- 16.4 ng/mL and 80.7 +/- 14.9 ng/mL in the H22 and control groups, respectively . These results indicate that IFN-gamma plays a significant role in the pathogenesis of gram-negative sepsis. J Virol, 1992 Aug, 66(8), 4720 - 31 Deletion analysis of two tandemly arranged virulence genes in myxoma virus, M11L and myxoma growth factor; Opgenorth A et al.; Myxoma virus (MYX) is a leporipoxvirus of rabbits that induces a lethal syndrome characterized by disseminated tumorlike lesions, generalized immunosuppression, and secondary gram-negative bacterial infection . A MYX deletion mutant (vMYX-GF- delta M11L) was constructed to remove the entire myxoma growth factor (MGF) coding sequence and that for the C-terminal five amino acids of the partially overlapping upstream gene, M11L . Unexpectedly, this deletion completely abrogates the capacity of MYX to cause the characteristic disease symptoms of myxomatosis . Upon inoculation of rabbits with vMYX-GF- delta M11L, recipient animals developed only a benign, localized nodule reminiscent of a Shope fibroma virus-induced tumor in which a single primary lesion appeared at the site of injection and then completely regressed within 14 days, leaving the animals resistant to challenge with wild-type MYX . No evidence of the purulent conjunctivitis and rhinitis that always accompany wild-type MYX infection was observed . To ascertain whether the attenuation observed in vMYX-GF- delta M11L was due to a combined effect of the MGF deletion and alteration of the upstream M11L gene, two additional MYX recombinants were constructed: an MGF- virus (vMYX-GF-) containing an intact M11L gene and an M11L- virus (vMYX-M11L-) containing an intact MGF gene . Infection with vMYX-GF- resulted in moderated symptoms of myxomatosis, but all clinical stages of the disease were still detectable . In contrast, disruption of M11L alone dramatically reduced the virus virulence, resulting in a nonlethal syndrome whose clinical course was nevertheless distinct from that of vMYX-GF- delta M11L . Upon inoculation with vMYX-M11L-, rabbits developed primary and secondary tumors which were larger and more circumscribed than those of wild-type MYX recipients . Whereas wild-type MYX infection always includes severe, purulent conjunctivitis and rhinitis, vMYX-M11L- recipients remained healthy and displayed only minimal signs of respiratory distress . By about 30 days after infection, the tumors induced by vMYX-M11L- had completely regressed and these animals were immune to challenge with wild-type MYX . Histological analysis indicated that tumors induced by vMYX-M11L- are much more heavily infiltrated with macrophages and heterophils and that the sites of viral replication are more edematous and necrotic than those of wild-type infection, suggesting that the host was able to mount a more vigorous inflammatory response to vMYX-M11L- infection.(ABSTRACT TRUNCATED AT 400 WORDS) Dan Med Bull, 1992 Aug, 39(4), 304 - 20 The molecular biology and diagnostics of Chlamydia trachomatis; Birkelund S; The rapid development of biotechnological methods provides the potential of dissecting the molecular structure of microorganisms . In this review the molecular biology of chlamydia is described . The genus Chlamydia contains three species C . trachomatis, C . psittaci, and C . pneumonia which all are important human pathogens . Chlamydia is obligate intracellular bacteria with a unique biphasic life cycle . The extracellularly chlamydial elementary bodies (EB) are small, metabolic inactive, infectious particles with a tight outer cell membrane . After internalization into host cells the chlamydial structure changes, they transform to reticulated bodies (RB) which become larger, metabolically active, and start to replicate . Fourtysix hrs post infection RB reorganizes to EB followed by burst of the inclusion . The structure of the EB outer membrane differs from the membrane of gram-negative bacteria since it is highly cross-linked by S-S bridges . There are, however, also similarities to gram-negative cell walls . The chlamydial major outer membrane protein, Omp1, forms pores and is closely associated with lipopolysaccharide, LPS . LPS, however, is more loosely associated with Omp1 than in other gram negative bacteria since incubation of EB with antibodies against LPS will liberate it from the chlamydial surface . Therefore the surface localized LPS may be important for chlamydial survival . OMP1 varies between the different serovar of C . trachomatis . Several very conserved regions are separated by variable domains . The variable domains are very antigenic and are localized at the surface of EB . After chlamydial internalization into the host cell transition to RB starts . Some of the early proteins are DnaK-like and groEL-like heat-shock proteins . The chlamydial DnaK-like protein is very antigenic . Patient serum samples will recognize the chlamydial DnaK-like protein . From the determined DNA sequence the amino acid sequence was determined . It was 57% homologous to the Eschrichia coli DnaK protein . Also the GroEL-like protein is antigenic and very conserved . Factors of importance for pathogenicity of chlamydia have not yet been found . The adhesin(s) is unknown, and no factor of importance for the inhibition of fusion between phagosome and host cell lysosomes has been described . A protein similar to the mip gene product of Legionella pneumofila may be a possible candidate for a pathogenicity factor . Diagnosis of C . trachomatis infections has been done by chlamydia cultivation in tissue culture cells, by immunofluorescence and by ELISA . A new method based on the polymerase chain reaction (PCR) has been developed . As primers sequences from the common plasmid were used . This method has high sensitivity and specificity and does not require live chlamydia.(ABSTRACT TRUNCATED AT 400 WORDS) APMIS, 1992 Aug, 100(8), 747 - 51 IgG subclass antibodies against Helicobacter pylori heat-stable antigens in normal persons and in dyspeptic patients; Andersen LP et al.; Measurement of serum IgG antibodies against Helicobacter pylori seems to be useful in the diagnosis of H . pylori infections . IgG subclass antibodies against H . pylori have, however, not been investigated thoroughly . In this study IgG1, IgG2, IgG3 and IgG4 antibody levels against H . pylori were measured using an ELISA technique in 187 normal adult persons and in 174 patients with dyspeptic symptoms, of whom 99 patients were H . pylori positive . None of the IgG subclass antibody levels were better than the total IgG level for the diagnosis of H . pylori infection . The discrimination between H . pylori-positive and H . pylori-negative patients was better with IgG1, IgG2 and IgG4 antibody levels than with IgG3 antibody level . IgG2 was the IgG subclass antibody that mainly contributed to the age-dependent increase in the IgG antibody level . This sustains the suspicion that cross-reactions between lipopolysaccharide (LPS) from H . pylori and LPS from other Gram-negative bacteria may occur. Clin Invest Med, 1992 Aug, 15(4), 318 - 30 A new bioactive molecule for improving vascular graft patency: exploratory trials in dogs; Akoum A et al.; Myxalin is a new bioactive molecule that we have isolated from the culture medium of Myxococcus xanthus, a non-pathogenic Gram negative bacterium . This glycopeptide possesses an antithrombotic effect in vivo and has been shown to promote human endothelial cell growth in vitro . With the object of exploring its ability to improve vascular graft healing and patency, myxalin was immobilized on 6 mm diameter knitted polyester prostheses using gelatin as a carrier, and the prosthesis was then implanted as an infrarenal abdominal arterial substitute in dogs for a period of 2 weeks . Two additional series of implantations were conducted for control purposes: one with gelatin-coated prostheses without myxalin, the other following normal preclotting of the polyester grafts . In order to select adequate sterilization conditions which can preserve the biological activity of myxalin, the prostheses were sterilized according to 3 different sterilization processes (gamma radiation and ethylene oxide either at 63 degrees C or 37 degrees C) . At the sacrifice, all grafts were patent . The myxalin treated prostheses exhibited improved blood compatibility in terms of fewer thrombotic deposits and significant inhibition of platelet and fibrinogen uptake on their luminal surfaces . In addition, the development of a thin collagenous internal capsule with endothelial cells secreting high levels of prostacyclin was observed at both anastomoses of the myxalin-treated grafts sterilized by gamma radiation. Appl Environ Microbiol, 1992 Aug, 58(8), 2543 - 51 Comparison of bioaerosol sampling methods in barns housing swine; Thorne PS et al.; The air in livestock buildings contains bioaerosol levels that are sufficiently high to cause adverse health effects in animals and workers . These bioaerosols are complex mixtures of live and dead microorganisms and their products as well as other aeroallergens . The effectiveness of sampling methods used for quantifying the very high concentrations of microorganisms in these environments has not been well studied . To facilitate an accurate assessment of respiratory hazards from viable organisms in agricultural environments, three bioaerosol sampling methods were investigated: the Andersen microbial sampler method (AMS), the all-glass impinger method (AGI), and the Nuclepore filtration-elution method (NFE) . These methods were studied in a parallel fashion in 24 swine confinement buildings . Measurements were taken in two seasons with three types of culture media in duplicate to assess total bacteria, gram-negative enteric bacteria, and total fungi . Methods were analyzed for the proportion of samples yielding data within the limits of detection, intraclass reliability, and correlation between methods . For sampling viable bacteria, the AMS had a poor data yield because of overloading and demonstrated weak correlation with the AGI . Conversely, the AGI and NFE gave sufficient numbers of valid data points (90%), yielded high intraclass reliabilities (alpha greater than or equal to 0.92), and were highly correlated with each other (r = 0.86) . The AGI and the NFE were suitable methods for assessing bacteria in this environment, but the AMS was not . The AMS was the only method that consistently recovered enteric bacteria (73% data yield) . For sampling fungi, the AGI and AMS both yielded sufficient data and all three methods demonstrated high intraclass reliability.(ABSTRACT TRUNCATED AT 250 WORDS) Am J Pathol, 1992 Aug, 141(2), 307 - 17 In vivo effects of endotoxin on intraepithelial mucosubstances in rat pulmonary airways . Quantitative histochemistry; Harkema JR et al.; Bacteria-induced bronchopneumonias are often characterized by an influx of neutrophils and excess mucus in pulmonary airways . This study determined how endotoxin, a component of gram-negative bacteria and a potent inflammatory agent, affects the ultrastructure of the mucociliary apparatus and the amount of stored intraepithelial mucosubstances in the main axial airways within the lung . Rats were intranasally instilled, once a day for 3 days, with endotoxin or saline (controls) . Animals were sacrificed 1, 2, or 7 days after the last instillation . Microdissected intrapulmonary axial airways (generations 8-11) from the right caudal lobes of infusion-fixed lungs were processed for light and electron microscopy . Morphometric techniques were used to determine the volume densities (Vs) of histochemically stained intraepithelial mucosubstances and numerical densities of airway epithelial cells . There were marked increases, compared with controls, in the amount of intraepithelial mucosubstances in the intrapulmonary axial airways at generations 8 and 11 in the right caudal lobes from endotoxin-instilled rats sacrificed 1, 2, and 7 days after the last instillation . There were significantly greater numbers of surface epithelial cells per length of basal lamina (i.e., hyperplasia) in endotoxin-exposed airways compared with airways from controls . This endotoxin-induced hyperplasia was due primarily to an increase in the number of mucus-secretory cells, which in endotoxin-exposed epithelium were columnar and contained numerous, large confluent, electronlucent, secretory granules composed of acidic and neutral glycoproteins . In contrast, secretory cells in airway epithelium from controls were cuboidal and contained small discrete, electron-dense, granules composed of only neutral glycoproteins . The numbers of ciliated cells and basal cells were similar in both control and endotoxin-exposed epithelium . Only endotoxin-exposed epithelium, however, contained atypical epithelial cells with numerous basal bodies, few cilia, and few apical secretory granules . These results indicate that repeated airway instillations of endotoxin induce an increase in the amount of intraepithelial mucosubstances, secretory cell hyperplasia, and excess luminal mucus in pulmonary airways . Therefore, endotoxin released from gram-negative bacteria may be partially responsible for the structural alterations, in the airway surface epithelium, which result in the excess luminal mucus observed in bacteria-induced bronchopneumonias. J Trop Med Hyg, 1992 Aug, 95(4), 271 - 5 Detection of Brucella melitensis and Brucella abortus by DNA amplification; Baily GG et al.; Suitable reaction conditions and oligonucleotide primers were sought for the detection of Brucella melitensis and Brucella abortus by the polymerase chain reaction . Primers were chosen from within the coding sequence of a gene encoding a 31 kDa B . abortus antigen . The test was shown to be sensitive, and specificity was demonstrated using DNA derived from a panel of Gram-negative pathogens . There was no detectable difference between B . melitensis and B . abortus in the sensitivity of the reaction or in the size of the amplification product . The technique should be applicable in the diagnosis of brucellosis. Am Rev Respir Dis, 1992 Aug, 146(2), 352 - 7 Inflammatory response to acute inhalation of endotoxin in asthmatic patients; Michel O et al.; Inhalation of 20 micrograms endotoxins (from the membrane of Gram-negative bacteria) has been reported to induce a bronchial obstructive response in asthmatic subjects . The aim of the present study was to evaluate in asthmatic patients the possibility of an inflammatory response to inhaled endotoxins . Eight patients with mild asthma were submitted to bronchial challenge tests, in a single-blind trial, on Day 1 with control solution and on Day 7 with 20 micrograms endotoxin of Escherichia coli (026:B6) . Local inflammatory response was indirectly evaluated by the degree of bronchial hyperresponsiveness (BHR) expressed as PD20 FEV1 histamine (the dose of histamine inducing a 20% decrease in FEV1) at 0, 6, 24, and 48 h and 7 days . Systemic inflammation was investigated by sequential blood determinations of total (and differential) white cells, complement anaphylatoxin C5a, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and C-reactive protein (CRP) . A significant (p < 0.01) bronchial obstructive response was demonstrable 45 min after lipopolysaccharide (LPS) inhalation, lasting 5 h . Comparing the level of BHR after control inhalation, a significant (p < 0.05) increase in BHR was shown 6 h after LPS, partially normalized at 24 and 48 h . A short peak in TNF-alpha at 60 min (p < 0.05) and an increase in total white blood cells (p < 0.01) and neutrophil polymorphonuclear neutrophils at 360 min (p < 0.05) and of CRP at 24 and 48 h (p < 0.05 and p < 0.01) were significant . The other blood parameters did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS) J Am Osteopath Assoc, 1992 Aug, 92(8), 1017 - 20 Update on monoclonal antibody therapy in the gram-negative sepsis syndrome; Hecker RB; Two multicenter controlled clinical trials of genetically engineered monoclonal antibodies directed against endotoxin, a potent mediator of inflammation in the gram-negative sepsis syndrome, were recently reported in the medical literature . One of these antiendotoxin antibodies was derived from a murine (mouse) source, and the other antibody was derived mainly from a human source (nebacumab {negative bacteria human monoclonal antibody}) . This article reviews recent literature concerning the use of these agents in the treatment of gram-negative sepsis syndrome . It also projects economic assessment data regarding the use of nebacumab in the United States. Z Gastroenterol, 1992 Aug, 30(8), 543 - 52 {Spontaneous bacterial peritonitis}; Press AG et al.; Patients with liver cirrhosis and ascites suffer from spontaneous bacterial peritonitis (SBP) in up to 25% . The typical clinical signs are abdominal pain with tenderness and fever . 30% have no signs of peritonitis . Then clinical worsening, encephalopathy, rising serum creatinine levels, and therapy resistant ascites may be the only clinical features . SBP must be differentiated from bacterascites and culture negative neutrocytic ascites by the polymorphonuclear neutrophil (PMN) count in the ascites and the presence of positive culture results, which has prognostic implications . Gram negative rods from the colon play an important etiological role in SBP . Gastrointestinal bleeding, lack of serum complement, a low ascites protein and the extent of intrahepatic shunts predispose to SBP . Then, prophylaxis with the comparable drugs neomycin and norfloxacin is indicated . Coexisting encephalopathy has to be treated by the therefore effective neomycin . Otherwise, norfloxacin is the drug of choice because of better acceptance and lower costs . Chemical parameters of the ascites (pH value less than 7.4; LDH and lactate greater than serum levels; glucose less than 50 mg%) help to assess the severity of peritonitis . The course of ascitic PMN under therapy and the time of persisting positive cultures can discriminate SBP from secondary peritonitis . Antibiotics of choice are amoxicillin-clavulanic acid and cefotaxime . Short course therapy (5 days) is a effective as long course therapy (10 days) . Today SBP is no more life-threatening because diagnosis, prophylaxis and therapy have improved . However, complication rate of patients with liver cirrhosis and ascites has not changed. Childs Nerv Syst, 1992 Aug, 8(5), 279 - 80 Brain abscess in infants; Krajewski R et al.; Brain abscesses are rare in infants and their clinical presentation is specific for this age group . Seven cases of brain abscess in infants aged 2-11 months are reported . The underlying cause was meningitis in four, sepsis in two, and unknown in one . Gram-negative organisms were cultured in 6 patients . The abscess size was 5 cm or more in five cases; in four there were multiple lesions . Two abscesses were aspirated and irrigated; four particularly large lesions were drained and repeatedly aspirated and irrigated . One craniotomy was done . There were two deaths, one in the postoperative period and the other 6 months after discharge . Follow-up information is available for four children, showing a good result in only one of them . Formation of an abscess should be diagnosed early, and close ultrasound monitoring or CT scanning in infants with bacterial meningitis and sepsis is essential . The prognosis in cases in which large/multiple abscesses develop is poor. Biokhimiia, 1992 Aug, 57(8), 1196 - 205 {Selective solubilization and biochemical analysis of R . prowazekii outer membrane proteins}; Emel'ianov VV; Solubilization of proteins from total membranes (a mixture of cytoplasmic and outer membranes) of Rickettsia prowazekii, a typical gram-negative bacterium, was studied using three different detergents . It was shown that isolated outer membranes and sarkosyl-insoluble material contain major polypeptides of 134, 31, 29.5 and 25 kDa as well as minor polypeptides of 78, 60, 42, and 17 kDa, while the total membranes--the same plus a great number of additional minor proteins . The material solubilized by octyl glucoside in the presence of MgCl2 contains exclusively major proteins (134, 31, 29.5, and 25 kDa) . No differential solubilization takes place upon membrane treatment with octyl glucoside in the absence of Mg2+ or with Triton X-100 . Rickettsial proteins are insensitive to trypsin in both whole cells and total membranes, unless the latter are presolubilized with octyl glucoside . Proteinase K degrades all of the total membrane proteins but only the 134 kDa polypeptide of whole cells . Upon immunoblotting predominantly the major outer membrane proteins (134, 31, and 20.5 kDa) and, to a lesser extent, the minor proteins (60, 42, and 17 kDa) interact with human convalescent serum. Br J Haematol, 1992 Aug, 81(4), 480 - 8 Modulation of tissue factor on human monocytes by cisplatin and adriamycin; Walsh J et al.; Coagulation disorders have been associated with the use of chemotherapeutic drugs . Pharmacological doses of cisplatin and adriamycin directly induced low levels of procoagulant on normal human blood monocytes and on a human myelomonocytic cell line, RC2a . Activity was maximal after 24 h and was not due to cell lysis as increasing drug doses which decreased cell viability were less effective . Procoagulant induction was markedly enhanced in the presence of bacterial lipopolysaccharide (LPS), with as little as 10-100 pg/ml LPS potentiating the cisplatin response by 2-5-fold and more than doubling the adriamycin response . Greater than 90% of the procoagulant activity was membrane-bound tissue factor as indicated by the factor VII-dependent generation of factor Xa by viable cells and by the neutralization of this activity by a monoclonal antibody to tissue factor . Tissue factor antigen was measured simultaneously by immunohistochemical staining and by cell ELISA . Blood monocytes activated with LPS expressed high levels of tissue factor antigen; by contrast, adriamycin and cisplatin did not appear to induce antigen expression, but to enhance the specific activity of that already present . Results suggest that membrane alterations which occur following treatment with DNA/RNA intercalating drugs, may result in a highly active form of monocyte/macrophage tissue factor which may contribute to the complications caused by activated coagulation . Secondary Gram-negative infection or cytokines released by an active immune response to a tumour may contribute to the procoagulant potential of these cytotoxic drugs. Surgery, 1992 Aug, 112(2), 188 - 93; discussion 193-4 Recombinant interleukin-1 receptor antagonist (IL-1ra): effective therapy against gram-negative sepsis in rats; Alexander HR et al.; BACKGROUND . Morbidity and mortality from bacterial sepsis remain high despite aggressive diagnostic and therapeutic intervention . Interleukin-1 has been implicated as mediator of the lethal effects of endotoxemia or bacterial sepsis . The current experiments were designed to evaluate the therapeutic efficacy of a human recombinant interleukin-1 receptor antagonist (IL-1ra) against polymicrobial gram-negative septicemia in rats . METHODS . Male rats underwent placement of indwelling carotid arterial and superior vena caval catheters followed by cecal ligation and puncture (CLP) . After 3 hours rats received either IL-1ra (10 mg/kg intravenous bolus followed by 5 mg/kg/hr) or an equal volume of vehicle intravenously for 24 hours . Heart rate, respirations, mean arterial blood pressure, and temperature were recorded at frequent intervals, and survival was assessed for 30 hours after CLP . RESULTS . There were no differences in vital signs between groups at baseline or before treatment, and all animals appeared ill with huddled posture, piloerection, and hyperventilation . Twenty-four hours after CLP, IL-1ra significantly ameliorated bradycardia (p = 0.01), hypothermia (p = 0.001), and hypotension (p = 0.05), and 30-hour survival was significantly improved (71% vs 20%, p less than 0.05) . CONCLUSIONS . IL-1ra lessens the acute hemodynamic, hypothermic, and mortal effects of gram-negative sepsis induced by CLP in rats . These data suggest that IL-1 receptor blockade may be an important new treatment strategy against overwhelming bacterial sepsis. J Immunol, 1992 Aug 1, 149(3), 918 - 24 Granulocyte colony-stimulating factor treatment protects rodents against lipopolysaccharide-induced toxicity via suppression of systemic tumor necrosis factor-alpha; Gorgen I et al.; Pretreatment with recombinant human granulocyte CSF (G-CSF) protected mice in two different models of septic shock . Intravenous injection of 250 micrograms/kg G-CSF to mice prevented lethality induced by 5 mg/kg LPS . Injection of 50 micrograms/kg G-CSF protected galactosamine-sensitized mice against LPS-induced hepatitis . In either case, this protection was accompanied by a suppression of LPS-induced serum TNF activity . In contrast, when galactosamine-sensitized mice were pretreated with 50 micrograms/kg murine recombinant granulocyte/macrophage CSF instead of G-CSF and subsequently challenged with LPS, serum TNF activity was significantly enhanced and mortality was increased . The suppressive effect of G-CSF on LPS-induced TNF production was also demonstrated in rats . In vivo, no TNF was detectable in the blood of LPS-treated rats, which had been pretreated with G-CSF . Ex vivo, alveolar macrophages, bone marrow macrophages, Kupffer cells, or peritoneal macrophages prepared from G-CSF-treated rats produced significantly less TNF upon stimulation with LPS than corresponding populations from control rats . However, when these macrophage populations were incubated with G-CSF in vitro, LPS-induced TNF production was unaffected . These data suggest that the G-CSF-mediated suppression of TNF production is not a direct effect of G-CSF on macrophages . To examine whether, independent of the protection against LPS, G-CSF treatment still activated neutrophils, it was demonstrated that granulocytes from G-CSF-treated rats were primed for PMA-induced oxidative burst and for ionophore/arachidonic acid-stimulated lipoxygenase product formation . The experiments of this study support the notion that G-CSF is a negative feedback signal for macrophage-derived TNF-alpha production during Gram-negative sepsis. N Engl J Med, 1992 Jul 23, 327(4), 234 - 40 Prophylactic intravenous administration of standard immune globulin as compared with core-lipopolysaccharide immune globulin in patients at high risk of postsurgical infection . The Intravenous Immunoglobulin Collaborative Study Group. {Necrobacillosis} Pedersen G, Hagelskjaer LH. Medicinsk afdeling B (haematologi) og klinisk mikrobiologisk afdeling, Aalborg Sygehus SydNecrobacillosis is an infection caused by the anaerobic Gram-negative rod Fusobacterium necrophorum . The infection is most common in previously healthy young adults and is characterised by sore throat followed by rigors, septicaemia and the formation of metastatic abscesses, often in the lungs . The infection has a certain mortality, which is reduced when early and sufficient treatment is administered . The treatment is a prolonged course of penicillin and/or metronidazole . Two case histories and a review of the literature are presented . The purpose of this article is to make the clinician aware of the syndrome, which is so characteristic that the diagnosis can be made from the clinical picture alone before bacteriological verification. JPEN J Parenter Enteral Nutr, 1992 Jul-Aug, 16(4), 353 - 8 Adaptation to a fish oil diet before inducing sepsis in rats prevents fatty infiltration of the liver; Lanza-Jacoby S et al.; Hypertriglyceridemia and fatty liver are common lipid abnormalities associated with Gram-negative sepsis . Fish oils have been shown to have beneficial effects in reducing plasma triglycerides (TG) . This study was designed to investigate whether fish oils would prevent the elevation of plasma TG and the accumulation of liver lipids during sepsis . One group of rats was fed a 10% menhaden oil diet and the other group was fed a 10% corn oil diet for 14 days . On the 14th day, sepsis was induced by injecting the rats with 8 x 10(7) live Escherichia coli colonies/100 g of body weight and the rats were fasted for 22 hours . The liver composition of total lipids and TG in the septic rats prefed the fish oil was lower than in the septic rats prefed the corn oil . In the rats adapted to the corn oil diet, lipids accumulated in the livers of the septic rats in comparison with the control rats . Hepatocytes isolated from the septic rats adapted to the corn oil diet showed an increased esterification of {1-14C}palmitate into TG and phospholipids than hepatocytes from the control rats . Feeding the fish oil diet instead of the corn oil diet before inducing sepsis reduced TG, cholesterol, and phospholipid synthesis by 58%, 79%, and 71%, respectively . The rise in TG synthesis in the septic rats prefed the corn oil diet was associated with an 89% increase in the activity of phosphatidate phosphohydrolase . There was no significant difference in the activities of glycerol-3-phosphate acyltransferase and phosphatidate phosphohydrolase between control and septic rats.(ABSTRACT TRUNCATED AT 250 WORDS) Appl Environ Microbiol, 1992 Jul, 58(7), 2245 - 9 Numerical taxonomy of gram-negative, nonmotile, nonfermentative bacteria isolated during chilled storage of lamb carcasses; Prieto M et al.; A numerical taxonomic study using 75 characters was performed with 132 strains of gram-negative, nonmotile, nonfermentative bacteria selected on the basis of lack of motility and Gram reaction among 1,200 cultures isolated during aerobic storage of lamb carcasses . At the 80% similarity level (SSM), eight clusters were formed . Strains in clusters 1 to 6 could be identified as members of the family Moraxellaceae and, more specifically, as members of the Psychrobacter-{Moraxella} phenylpyruvica subgroup . Of these strains, clusters 1 and 2 (88 strains) were identified as {Moraxella} phenylpyruvica and cluster 3 (15 strains) was identified as Psychrobacter immobilis . Clusters 4, 5, and 6 were not identifiable with any species . Clusters 7 and 8 consisted of 14 strains considered nonmotile variants of Pseudomonas fragi . The highest separation indices corresponded to acid production from certain carbohydrates (melibiose, L-arabinose, and cellobiose) . Although strains of Psychrobacter-Moraxella clusters were relatively frequently identified at the completion of slaughter, very few cultures were detected on spoiled carcasses . It appears, therefore, that this group of organisms has only low spoilage potential. J Clin Invest, 1992 Jul, 90(1), 97 - 106 Interactions of surfactant protein D with bacterial lipopolysaccharides . Surfactant protein D is an Escherichia coli-binding protein in bronchoalveolar lavage; Kuan SF et al.; Surfactant protein D (SP-D) is a collagenous glycoprotein that is secreted into the pulmonary airspaces by alveolar type II and nonciliated bronchiolar cells . SP-D exhibits Ca(++)-dependent carbohydrate binding in vitro and is structurally related to the collagenous C-type lectins, including serum conglutinin, serum mannose-binding proteins, and surfactant protein A . Preliminary studies showed calcium- and saccharide-dependent binding of fluorescein-conjugated or radioiodinated SP-D to a variety of microorganisms, including Gram-negative bacteria and fungi . A laboratory strain of Escherichia coli (Y1088) was chosen to further examine the mechanism(s) of binding . Binding of SP-D to Y1088 was time dependent, saturable, and inhibited by cold SP-D or competing saccharides; Scatchard analysis gave a Kd of 2 x 10(-11) M . At higher concentrations, SP-D also caused Ca(++)-dependent agglutination of Y1088 that was inhibited by alpha-glucosyl-containing saccharides, antisera to the carbohydrate-binding domain of SP-D, or Y1088 LPS . Lectin blots showed specific binding of 125I-SP-D to Y1088 LPS, as well as LPS from other several strains of enteric Gram-negative bacteria . Immunogold studies demonstrated strong and uniform surface labeling of the bacteria . Rat and human bronchoalveolar lavage (BAL) caused Ca(++)-dependent agglutination of E . coli that was dose dependent and inhibited by competing saccharides or anti-SP-D . SP-D was selectively and efficiently adsorbed from rat BAL by incubation with E . coli, and incubation of E . coli with radiolabeled rat type II cell medium revealed that SP-D is the major E . coli-binding protein secreted by freshly isolated cells in culture . We suggest that SP-D plays important roles in the lung's defense against Gram-negative bacteria. Br J Ophthalmol, 1992 Jul, 76(7), 424 - 7 Possible environmental sources of Acanthamoeba spp in contact lens wearers; Seal D et al.; The water supply and dust samples from the home environment (bathrooms and kitchens) of 50 wearers of contact lenses (CLs) were cultured for the presence of free-living amoebae . CL cases, solutions, and water taps were cultured for bacteria, which amoebae require for growth . Acanthamoeba spp were isolated from water drawn from six bathroom cold water taps (tank supplied), five in the presence of limescale, and from one kitchen cold water tap (mains supplied) . There was an association between the presence of limescale in water and direct culture for free-living amoebae, suggesting that scale provides a favourable microenvironment for amoebae . Acanthamoebae were also found in dust from around one washbasin . Nineteen of 50 CL cases, 12/122 CL care rinsing solutions, and 59/100 cold water taps yielded Gram negative bacteria which could be ingested by amoebae . It is concluded from this study that CLs should not be washed in first-drawn tank-fed cold water, especially if limescale is present, and that soft CLs should be rinsed in manufactured single-use, sterile solutions . Rigid CL and CL cases should only be washed with boiled tap water (preferably hot), or single-use sterile solutions, and stored dry to prevent multiplication of amoebae and Gram negative bacteria. Infect Immun, 1992 Jul, 60(7), 2769 - 76 Legionella pneumophila lipopolysaccharide activates the classical complement pathway; Mintz CS et al.; Legionella pneumophila is a gram-negative bacterium capable of entering and growing in alveolar macrophages and monocytes . Complement and complement receptors are important in the uptake of L . pneumophila by human mononuclear phagocytes . The surface molecules of L . pneumophila that activate the complement system are unknown . To identify these factors, we investigated the effects of L . pneumophila lipopolysaccharide (LPS) on the classical and alternative complement pathways of normal human serum by functional hemolytic assays . Although incubation of LPS in normal human serum at 37 degrees C resulted in the activation of both pathways, complement activation proceeded primarily through the classical pathway . Activation of the classical pathway by LPS was dependent on natural antibodies of the immunoglobulin M class that were present in various quantities in sera from different normal individuals but were absent in an immunoglobulin-deficient serum obtained from an agammaglobulinemic patient . Additional studies using sheep erythrocytes coated with LPS suggested that the antibodies recognized antigenic sites in the carbohydrate portion of LPS . The ability of LPS to interact with the complement system suggests a role for LPS in the uptake of L . pneumophila by mononuclear phagocytes. Clin Orthop, 1992 Jul, (280), 175 - 8 Case report of an unusual cause of low back pain . Intervertebral diskitis caused by Eikenella corrodens; Noordeen MH et al.; A 42-year-old man suffered from low back pain caused by intervertebral diskitis . The condition was diagnosed on plain roentgenogram and computed tomography scans . The infected area was biopsied and grew Eikenella corrodens, a gram-negative anaerobic rod, which grows slowly only after culture on blood agar in 5-10% carbon dioxide . This is the first reported case of E . corrodens intervertebral diskitis causing acute low back pain . Recognition of this organism in this condition emphasizes the importance of aerobic and anaerobic cultures of infected disks . The organism has unusual antibiotic sensitivities . The infection, once appropriately treated, responded rapidly. Am J Surg Pathol, 1992 Jul, 16(7), 650 - 7 Immunocytochemical identification of Rochalimaea henselae in bacillary (epithelioid) angiomatosis, parenchymal bacillary peliosis, and persistent fever with bacteremia; Reed JA et al.; We report the immunocytochemical identification of Rochalimaea henselae, a newly recognized fastidious, Gram-negative, Warthin-Starry-positive organism, as the common pathogen in bacillary angiomatosis (BA), bacillary peliosis (BP) of the liver and spleen, and persistent fever with bacteremia in immunocompromised patients . Immunogenic proteins of the R . henselae strain isolated from the blood of a febrile immunocompromised patient with BP of the liver were used to produce primary immune serum in rabbits . Using immunocytochemical procedures, the polyclonal antiserum reacted strongly not only with the immunizing strain of the bacteria, but also with other blood isolates of R . henselae (five cases) from both immunocompromised and immunocompetent patients and with the organisms present in the tissue lesions of cutaneous BA (five cases) and BP of the liver (two cases) and spleen (one case) . The blood isolates and BA and BP tissue samples were obtained from widely separated geographic areas . The antiserum was weakly cross-reactive with cultures of Rochalimaea quintana, an organism closely related to R . henselae, but this reactivity was eliminated by specific adsorption . The antiserum did not cross-react with the Warthin-Starry-positive organisms associated with cat scratch disease (Afipia felis), syphilis (Treponema pallidum), Lyme disease (Borrelia burgdorferi) or chronic active gastritis (Helicobacter pylori) . Likewise, the antiserum did not identify organisms in eight cases of Kaposi's sarcoma, a disorder of immunocompromised patients that is clinically similar to BA . Further studies are needed to determine the prevalence of this newly recognized organism as well as its possible involvement in other angioproliferative diseases. Mikrobiyol Bul, 1992 Jul, 26(3), 233 - 41 {In vitro activity of various antibiotic agents against gram-negative nosocomial bacteremia pathogens}; Gur D et al.; Empiric therapy is essential in Gram-negative nosocomial bacteremia . Therapy is initiated according to the most frequently isolated organisms and their susceptibility profiles . In order to determine the appropriate antibiotics for this purpose, a study was conducted in 176 blood isolates in Hacettepe University Hospitals . Antibiotic susceptibilities were determined by microbroth dilution tests . The results showed amikacin, ofloxacin and ciprofloxacin to be the most effective antibiotics in-vitro . It is suggested that these agents should be employed in empirical therapy until the causative agent is defined. Leber Magen Darm, 1992 Jul, 22(4), 156 - 9 {Spontaneous bacterial peritonitis in a patient with decompensated alcoholic cirrhosis of the liver}; Nechwatal R et al.; Spontaneous bacterial peritonitis (SBP) constitute a rare complication of cirrhosis of the liver with a high mortality rate . Unspecific sings of decompensation like increasing elaboration of ascites or the development of hepatic encephalopathy are often prevailing . Fever and peripheral blood leukocytosis as well as abdominal sings of peritonitis are not rarely completely missing . There is a strong suspicion of SBP with an ascitic polymorphonuclear count of greater than 500/mm3 . Determination of lactate and pH in the ascitic fluid can increase diagnostic sensitivity and specificity if the leukocyte count is dubious . Gram negative rods predominate with over 70% whereas anaerobic organisms appear to be very rare . A 49 year old patient is presented and diagnostic and therapeutic strategies reviewed . In view of the high mortality every clinical deterioration of patients with cirrhosis should alert the physician of the presence of SBP. Vet Pathol, 1992 Jul, 29(4), 269 - 77 Microscopic and ultrastructural studies of necrotizing hepatopancreatitis in Pacific white shrimp (Penaeus vannamei) cultured in Texas; Frelier PF et al.; Granulomatous hepatopancreatitis of unknown etiology has been considered an important disease of Texas shrimp mariculture since 1985 . Samples of Pacific white shrimp (Penaeus vannamei) were collected during 1986, 1987, and 1990 from three farms and an experimental mariculture facility with histories of production loss and increased mortality rates . Histologic and ultrastructural examination of shrimp from the four sites demonstrated two morphologically distinct, Gram-negative, double-enveloped, intracytoplasmic bacteria in necrotic hepatopancreatic epithelium . The more numerous small, pleomorphic rod as well as the helical organism are both taxonomically unclassifiable . The helical organism lacked ultrastructural characteristics of previously described helical or spiral bacteria . The relationship between the two organisms is unknown, but the pleomorphic rod is thought to play a major role in the disease . The role of a bacterial agent(s) in subsequent disease episodes is suggested by the observation that the use of oxytetracycline-medicated feed resulted in increased production and survival . Hepatopancreatic tubular epithelial necrosis and shrimp mortality correlated directly with the extent of infection by the small pleomorphic rod . Individual discrete bacteria were identified microscopically by Steiner and Steiner's method . Three major developmental stages of the disease were characterized based on the extent and number of hepatopancreatic tubular epithelial cells containing bacteria, the degree of tubular interstitial inflammation, and the extent and chronicity of tubular necrosis . Additional studies are needed to clarify the roles of the different bacteria identified and the potential role of environmental factors on the disease process. Antimicrob Agents Chemother, 1992 Jul, 36(7), 1499 - 503 Comparison of 5 milligrams of netilmicin per kilogram of body weight once daily versus 2 milligrams per kilogram thrice daily for treatment of gram-negative pyelonephritis in children; Vigano A et al.; The efficacy and safety of netilmicin, 5 mg/kg of body weight once daily or 2 mg/kg thrice daily for 10 days, for the treatment of gram-negative pyelonephritis in children were compared in a prospective, randomized trial . Explicit criteria were used to define the site of infection, treatment outcome, and adverse effects . Netilmicin was given to 74 children once daily and to 70 children three times daily . At 1 week posttreatment, 73 (99%) of 74 children treated with netilmicin once daily and 70 (100%) of 70 children treated with netilmicin three times daily were cured . At 4 weeks posttreatment, no relapse was detected and the rate of reinfection was essentially identical in the two treatment groups . Peak serum netilmicin concentrations were higher in patients given the once-daily regimen, whereas a higher trough level was detected in patients given the three-times-daily regimen . Nephrotoxicity, which was defined as an increase in the serum creatinine level of greater than or equal to 0.3 mg/dl over the baseline, was rare (3%) and reversible and occurred regardless of the treatment regimen . Ototoxicity, which was assessed by pure-tone audiometry (250 to 8,000 Hz) and brain stem-evoked response (6,000 Hz), occurred in 2 of 32 children who were evaluated . In these two children, who were given the once-daily regimen, wave V was not evokable monolaterally below 25 and 40 dB normal hearing level, respectively . Thus, it may be possible to treat childhood pyelonephritis with netilmicin once daily . However, this new approach needs to be confirmed in other studies. Int J Syst Bacteriol, 1992 Jul, 42(3), 451 - 8 Flexibacter ovolyticus sp . nov., a pathogen of eggs and larvae of Atlantic halibut, Hippoglossus hippoglossus L; Hansen GH et al.; A psychrotrophic Flexibacter sp., Flexibacter ovolyticus sp . nov., was isolated from the adherent bacterial epiflora of Atlantic halibut (Hippoglossus hippoglossus L.) eggs and was shown to be an opportunistic pathogen for halibut eggs and larvae . The strains which we isolated had the enzymatic capacity to dissolve both the chorion and the zona radiata of the egg shells . A total of 35 isolates were characterized by using morphological and biochemical tests . These strains were rod shaped, gram negative, Kovacs oxidase positive, and pale yellow and exhibited gliding motility . They did not produce acid from any of the wide range of carbohydrates tested . Our isolates had the ability to degrade gelatin, tyrosine, DNA, and Tween 80 . Starch, cellulose, and chitin were not degraded . The strains were catalase and nitrate reductase positive, did not produce H2S, and did not grow under anaerobic conditions . F . ovolyticus resembles Flexibacter maritimus, but differs from the latter species in several biochemical and physiological characteristics . DNAs from F . ovolyticus strains had guanine-plus-cytosine contents which ranged from 30.3 to 32.0 mol% (strains EKC001, EKD002T {T = type strain}, and VKB004), and DNA-DNA hybridization studies revealed levels of relatedness between F . ovolyticus EKD002T and F . maritimus NCMB 2154T and NCMB 2153 of 42.7 and 30.0%, respectively . Compared with previously described Cytophaga and Flexibacter spp . with low guanine-plus-cytosine contents, F . ovolyticus constitutes a new species . Strain EKD002 (= NCIMB 13127) is the type strain of the new species. Acta Gastroenterol Belg, 1992 Jul-Aug, 55(4), 333 - 40 {Prevention of bacterial infection using selective intestinal decontamination in patients with cirrhosis admitted to intensive care . Controlled study in 120 patients}; Henrion J et al.; All cirrhotic patients admitted on a medical intensive care unit, were included in a randomized trial of selective intestinal decontamination provided there was no infection on admission . The selective intestinal decontamination consisted of a regimen of 3 oral, nonabsorbable antibiotics for the 74 first patients (Neomycin 1 gr, Colistin 1.500.000 U, Nystatin 1.000.000 U, every 6 hours), then of norfloxacin, 400 mg BID for the following patients . The duration of treatment was at least 5 days . Of the 120 patients, initially randomized to receive or not the treatment, 26 were ultimately excluded, mainly (18 cases) because of infection present but unrecognized at the time of admission . Ninety four patients were thus compared for the efficiency of the treatment, 45 in the treated group and 49 in the not treated group . The results showed a significant reduction of the episodes of septicemia in the treated group (4 versus 12, P = 0.044) . This reduction was evident only for septicemia due to gram negative germs . Mortality was unaffected . When the risk factors were studied, bacterial infection was linked to the degree of hepatic failure . We recommend selective intestinal decontamination for cirrhotic patients admitted on intensive care unit, particularly when hepatic function is poor. Wiad Lek, 1992 Jul, 45(13-14), 514 - 8 {Lyme disease--also a childhood disease}; Wygledowska G; In the light of a survey of the world literature Lyme borreliosis, an epidemic disease caused by gram-negative organisms Borrelia burgdorferi is described . The disease has three phases with involvement of the skin, the nervous system, the cardiovascular system and joints . Treatment with antibiotics is effective . The disease lies in the fields of interest of various specialties including paediatrics. Spec Care Dentist, 1992 Jul-Aug, 12(4), 153 - 6 The role of salivary function on oropharyngeal colonization; Gibson G et al.; Aspiration of oropharyngeal flora is the most common route of acquiring Gram-negative pneumonia, a major nosocomial infection . Epidemiologic studies indicate that the elderly are at increased risk for developing these life-threatening pneumonias . The primary objective of this study was to determine the effects of salivary oral defenses against Gram-negative colonization . The study population consisted of 41 male outpatients, age 70 and older, seen at the Denver VAMC . The group included subjects with both diminished and normal salivary flow . Each subject answered a questionnaire regarding overall health, medication use, and symptoms of salivary dysfunction . We then collected whole saliva, unstimulated and stimulated parotid saliva, and performed a throat swab on each patient . For each throat culture, analysis was done to identify Gram-negative bacteria . Flow rates between colonized (n = 6) and noncolonized subjects (n = 34) were compared . While there were no significant differences in the flow rates between the two groups, a trend was noticed in that flow rates were lower for all three flow measures in the colonized group (whole, 22% decrease; unstimulated, 22% decrease; and stimulated, 28% decrease) . These preliminary findings suggest that subjects with diminished salivary flow may possibly be at increased risk for oropharyngeal Gram-negative colonization . Research on the role that saliva plays in oropharyngeal bacterial colonization is continuing. Indian Pediatr, 1992 Jul, 29(7), 871 - 4 Chest radiographs in neonatal septicemia; Faridi MM et al.; Chest radiographs of 63 culture proven cases of neonatal septicemia were evaluated in this prospective study . Gram negative septicemia was responsible for 76.2% cases . Radiological abnormalities were observed in 27 cases (42.8%) . Seven of these had no respiratory distress . The findings were right sided infiltrates (27%); hyperinflation (7.9%), bronchopneumonia (6.3%) and pneumothorax (1.6%) . Increasing gestational age, late onset of illness (greater than 3 days) and presence of respiratory signs of distress had a positive correlation with presence of X-ray findings . Term newborns with respiratory distress of late onset sepsis (greater than 3 days) had significantly higher number (p less than 0.05) of abnormal radiographs . Presence of radiological abnormality neither influenced the clinical outcome nor was affected by the causative organisms . The practice of doing a chest radiograph routinely in cases of neonatal septicemia is justified irrespective of presence of respiratory signs of distress. Can J Microbiol, 1992 Jul, 38(7), 614 - 7 Binding of mutagenic pyrolyzates to fractions of intestinal bacterial cells; Zhang XB et al.; The binding of mutagenic pyrolyzates to cell fractions from some gram-negative intestinal bacteria and to thermally treated bacterial cells was investigated . 3-Amino-1,4-dimethyl-5H-pyrido{4,3-b}indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido{4,3-b}indole (Trp-P-2) were effectively bound by several of the bacterial cells . The cell wall skeletons of all bacteria effectively bound Trp-P-1 and Trp-P-2 . Their cytoplasmic fractions retained Trp-P-1 and Trp-P-2, but to a lesser extent than the cell wall skeletons . 2-Amino-3-methylimidazo{4,5-f}quinoline (IQ) was not found in their cytoplasmic fractions . These cell wall skeletons also bound 2-amino-6-methyldipyrido{1,2-a:3',2'-d}imidazole (Glu-P-1), 2-amino-5-phenylpyridine (Phe-P-1), IQ, 2-amino-3,4-dimethylimidazo{4,5-f}quinoline (MeIQ), and 2-amino-3,8-dimethylimidazo{4,5-f}quinoxaline (MeIQX) . The amount of each mutagen bound differed with the type of mutagen and the bacterial strain used . The outer membrane of Escherichia coli IFO 14249 showed binding of about 123.7 micrograms/mg of Trp-P-2, and its cytoplasmic membrane bound 57.14 micrograms/mg . Trp-P-2 bound to the bacterial cells was extracted with ammonia (5%), methanol, and ethanol but not with water. Immunol Today, 1992 Jul, 13(7), 271 - 6 Lipopolysaccharide antagonists; Lynn WA et al.; Bacterial lipopolysaccharide (LPS) is a potent and pleiotropic stimulus of immune cells . LPS has important clinical relevance because it has a direct role in the pathogenesis of Gram-negative bacterial infection . The lipid A moiety of LPS is responsible for the toxic effects of LPS . The identification of structural analogs and precursors of lipid A, which are apparently competitive antagonists of the biological actions of LPS, is strong evidence that the actions of LPS are mediated by a specific LPS receptor or family of receptors . Identification and analysis of these LPS receptors with LPS antagonists should help to define the pathways of cellular activation by LPS and lead to the development of novel anti-LPS strategies in the therapy of bacterial diseases. Proc Natl Acad Sci U S A, 1992 Jul 1, 89(13), 5735 - 9 In vivo production of a stable single-stranded cDNA in Saccharomyces cerevisiae by means of a bacterial retron; Miyata S et al.; Gram-negative bacteria such as Myxococcus xanthus, Stigmatella aurantiaca, and Escherichia coli contain retroelements called retrons . Retrons consist of the msr-msd region and the gene for reverse transcriptase (RT), which are essential for the production of the branched RNA-linked ms-DNA (multicopy single-stranded DNA) . In this study, we attempted to produce msDNA in the yeast Saccharomyces cerevisiae . Retron Ec67 from E . coli, which is responsible for the production of msDNA-Ec67, was cloned under the GAL10 promoter in a 2-microns-based plasmid . msDNA thus produced was detected by extending the 3' end of the msDNA by avian myeloblastosis virus RT . This yielded a main product of 117 nucleotides . Treatment of this product with RNase A resulted in a DNA of 105 nucleotides . These results are in good agreement with the structure of msDNA-Ec67 . The production of msDNA-Ec67 was further confirmed by Southern blot hybridization . The msDNA production was dependent upon the bacterial RT gene in the clone and was increased severalfold when the RT gene of retron Ec67 was placed in front of the msr-msd region . The potential of msDNA as a eukaryotic vector producing a stable single-stranded DNA as well as RNA is discussed. Am J Respir Cell Mol Biol, 1992 Jul, 7(1), 81 - 9 Endotoxin enhancement of lymphocyte adherence to cultured sheep lung microvascular endothelial cells; Jones M et al.; The most common predisposing factor for development of the adult respiratory distress syndrome is gram-negative sepsis . Our previous studies have shown that a single infusion of Escherichia coli endotoxin into sheep causes early sequestration of lymphocytes in the lungs' microcirculation . In this report, we examined the effects of endotoxin on sheep lymphocyte adherence to sheep pulmonary microvascular endothelial cells in vitro . Endothelial cells were exposed to endotoxin, and subsequent adherence of 51Cr-labeled lymphocytes was measured in a monolayer adhesion assay . Endotoxin enhanced adherence of lymphocytes isolated from blood and caudal mediastinal node (CMN) lymph in a time- and dose-dependent manner . Adherence of CMN lymphocytes increased from a control value of 13.6 +/- 1.6% to 29.9 +/- 3.1% after 4 h of treatment with 1 microgram/ml endotoxin . Both B and T lymphocytes contributed to the increased adherence . Pretreatment of the endothelial cells with cycloheximide revealed that the endotoxin-enhanced adherence was partially dependent upon protein synthesis . Morphologic studies revealed that enhanced adherence was accompanied by a 5-fold increase in migration of lymphocytes between endothelial cells . In contrast to human umbilical vein endothelial cells, antibodies to the known lymphocyte adherence molecules, lymphocyte function-associated antigen (LFA-1), CD-44, and the lymphocyte homing receptor (LECAM-1), were ineffective in blocking adherence to the sheep pulmonary endothelial cells . We conclude that the acute sequestration of lymphocytes in the pulmonary microcirculation of sheep after endotoxin administration is due to increased adhesive properties of the endothelial cells . Our data suggest that this adherence is mediated by as yet undescribed mechanisms that may be unique to pulmonary microvascular endothelium. Immunol Lett, 1992 Jul, 33(2), 135 - 8 Murine ascitic fluids contain varying amounts of an inhibitor that interferes with complement-mediated effector functions of monoclonal antibodies; Appelmelk BJ et al.; The ability of murine monoclonal antibodies (mAbs), directed to the inner core of Gram-negative bacterial lipopolysaccharide (LPS, endotoxin), to enhance complement-mediated killing of bacteria, was investigated . The mAbs were tested as present in ascitic fluid . It was found that ascites contains an factor that inhibited the activity of complement . This effect was evident in assays for complement-mediated lysis of antibody-coated Gram-negative bacteria (bacterial killing) or of opsonised red blood cells . Moreover, the amount of inhibitor was found to vary from one ascites to another and spanned a 60-fold range . Thus, in vitro or in vivo experiments where complement is known to play a determining role may yield incorrect results when ascites is used as a source of antibody; the use of ascites prepared from irrelevant antibody as a negative control does not eliminate this problem. Scand J Gastroenterol, 1992 Jun, 27(6), 453 - 8 Quantification of lipopolysaccharides in human bile with or without gram-negative bacteria; Osnes T et al.; Lipopolysaccharide (LPS) was assayed in 78 samples of human common-duct bile, obtained at endoscopic retrograde cholangiography . The LPS was assayed by a chromogenic limulus amebocyte lysate (LAL) test, after dilution of bile samples in heparinized plasma and inactivation of inhibitors . The assay was not influenced by other biliary constituents, as demonstrated by the recovery of standards . Bile pigments did not influence the results . The LAL test was positive in 60 of the samples, 59 of which had a positive culture for gram-negative bacteria or Candida sp . The levels of LPS were significantly correlated to the total number of bacteria (n = 16, R = 0.55, p less than 0.05) . The median LPS level was 35,250 ng/l and showed a very large variation (140 ng/l to 27.8 mg/l) . In four of the samples gram-negative bacteria were present, but no LPS could be detected . The study demonstrates the presence of LPS in great quantities in human bile and supports the feasibility of using the LAL test on bile samples . The presence of LPS (within the detection limit) appears to be associated with local microbial colonization. Eur Respir J, 1992 Jun, 5(6), 675 - 9 Branhamella catarrhalis respiratory infections; Barreiro B et al.; Branhamella catarrhalis is an aerobic Gram-negative diplococcus . It has been traditionally regarded as an oropharyngeal commensal and until recently was only identified as a pathogen in cases of bronchopulmonary infections . The aim of this study was to analyse the characteristics of the respiratory infections caused by B . catarrhalis and to know the antibiotic susceptibility of this microorganism . We retrospectively studied 32 lower respiratory tract infections, caused by B . catarrhalis (20 cases of bronchial infection and 12 cases of pneumonia), diagnosed between 1988-1989 in our hospital . All patients had an underlying disease; chronic obstructive pulmonary disease (COPD) and chronic heart disease being the most frequent . The aetiological diagnostic procedures were: sputum culture in 28 cases (15 in pure culture and 13 mixed), protected specimen brush (PSB) in three cases and transthoracic needle aspiration (TNA) in one case . Twenty B . catarrhalis isolates were penicillin and ampicillin-resistant, 11 in the pneumonia group and 9 in the bronchial infection group . All isolates were sensitive to amoxycillin-clavulanic acid and second generation cephalosporin . In our group four patients died . We conclude that B . catarrhalis is a not infrequent cause of respiratory infection, particularly in COPD patients, and that the high incidence of antibiotic resistance to penicillin and ampicillin should be taken into account before considering an empirical antibiotic treatment. Clin Infect Dis, 1992 Jun, 14(6), 1213 - 28 Gram-negative sepsis and the adult respiratory distress syndrome; Martin MA et al.; Gram-negative sepsis has dramatically increased in frequency throughout the twentieth century in the United States . Currently, approximately 200,000 patients develop gram-negative sepsis each year in this country . Of these, about one-quarter develop the adult respiratory distress syndrome (ARDS) . Among these critically ill patients, mortality is estimated at 60%-90% . In the complex series of events leading to acute lung injury in gram-negative sepsis, endotoxin is the proximal mediator . Although endotoxin may be capable of causing direct injury to the pulmonary endothelium, its primary role is as a trigger activating inflammatory agents, including complement, neutrophils, and platelets, and inducing the production of cytokines and arachidonic acid metabolites . The end results are impairment of the endothelial barrier, diffusely increased capillary permeability, and adherence of neutrophils to the endothelium with subsequent migration into the tissues . The consequent clinical syndrome is one of acute respiratory distress with pulmonary edema, poorly compliant lungs, and refractory hypoxemia . Endothelial injury often becomes widespread, leading to the failure of multiple organs, including the kidneys, brain, intestine, and liver . Conventional therapy consists of supplemental oxygen, positive end-expiratory pressure, inotropic agents, fluid management, and antibiotics aimed at the offending pathogen . Recent discoveries regarding the mediators of sepsis as well as the expansion of the biotechnological armamentarium have provided clinicians with a plethora of new tools with which to manipulate the host's inflammatory response . The challenge for the next decade will be to ensure the safety, efficacy, and cost-effective use of these expensive but potentially lifesaving immunomodulators, singly or in combination, as adjuvant therapy. Crit Care Med, 1992 Jun, 20(6), 746 - 50 Septic shock in patients with cirrhosis: hemodynamic and metabolic characteristics and intensive care unit outcome; Moreau R et al.; OBJECTIVES: To examine the hemodynamic and metabolic characteristics and ICU outcome of septic shock in patients with cirrhosis . DESIGN: Prospective, comparative study . Measurements performed in the first 24 hrs of septic shock . SETTING: A general hospital ICU . PATIENTS: Twelve patients with cirrhosis and 23 patients without cirrhosis admitted for septic shock . MEASUREMENTS AND MAIN RESULTS: Arterial pressure was measured using an arterial catheter . Pulmonary arterial and right atrial pressures were measured by using a pulmonary artery catheter . Cardiac output was determined by using the thermodilution method . Pulmonary arterial L-lactate plasma concentrations were measured using an automated spectrophotometer, and blood temperature was measured using a cardiac output computer . Arterial and mixed venous PO2, PCO2, and pH values were measured by using specific electrodes . Oxygen saturations and hemoglobin concentrations were measured using a hemoximeter . Patients with cirrhosis had decompensated liver disease (grade C of the Child-Pugh classification) . The number of Gram-negative infections and therapeutic interventions were similar in both groups . Patients with cirrhosis had higher cardiac indices (5.14 +/- 0.52 {SE} vs . 3.91 +/- 0.30 L/min/m2, p less than .05), plasma lactate concentrations (9.0 +/- 2.0 vs . 5.2 +/- 0.7 mmol/L, p less than .05) and ICU mortality rates (100% vs . 43%, p less than .05), and lower blood temperatures (35.5 +/- 0.6 vs . 37.6 +/- 0.2 degrees C, p less than .05) than patients without cirrhosis . Systemic vascular resistance, arterial pressure, pulmonary arterial pressure, oxygen delivery and consumption, and arterial and mixed venous acid-base status were not significantly different between the two groups . CONCLUSIONS: In patients with cirrhosis, septic shock was characterized by severe liver dysfunction, low blood temperature, marked increases in cardiac index and lactic acidemia, and a 100% ICU mortality rate . These findings should be taken into account if patients with cirrhosis are to be included in controlled studies on septic shock. J Bacteriol, 1992 Jun, 174(11), 3429 - 38 Localization of cytochromes to the outer membrane of anaerobically grown Shewanella putrefaciens MR-1; Myers CR et al.; In gram-negative bacteria, numerous cell functions, including respiration-linked electron transport, have been ascribed to the cytoplasmic membrane . Gram-negative bacteria which use solid substrates (e.g., oxidized manganese or iron) as terminal electron acceptors for anaerobic respiration are presented with a unique problem: they must somehow establish an electron transport link across the outer membrane between large particulate metal oxides and the electron transport chain in the cytoplasmic membrane . When the metal-reducing bacterium Shewanella putrefaciens MR-1 is grown under anaerobic conditions and membrane fractions are purified from cells lysed by an EDTA-lysozyme-polyoxyethylene cetyl ether (Brij 58) protocol, approximately 80% of its membrane-bound cytochromes are localized in its outer membrane . These outer membrane cytochromes could not be dislodged by treatment with chaotropic agents or by increased concentrations of the nonionic detergent Brij 58, suggesting that they are integral membrane proteins . Cytochrome distribution in cells lysed by a French press protocol confirm the localization of cytochromes to the outer membrane of anaerobically grown cells . This novel cytochrome distribution could play a key role in the anaerobic respiratory capabilities of this bacterium, especially in its ability to mediate manganese and iron reduction. Infect Immun, 1992 Jun, 60(6), 2506 - 13 Binding and neutralization of endotoxin by Limulus antilipopolysaccharide factor; Warren HS et al.; In order to examine the ability of Limulus antilipopolysaccharide factor (LALF) to bind lipopolysaccharide (LPS), we purified LALF to homogeneity from Limulus amoebocyte lysate and coupled it covalently to agarose beads . LALF-coupled beads captured more tritiated LPS from rough and smooth strains of gram-negative bacteria than did control human serum albumin-coupled beads . Unlabeled homologous and heterologous LPS competed for the binding of 3H-LPS to LALF-coupled beads . LALF bound LPS in a dose-dependent manner as assessed by the precipitation of LPS-LALF complexes with 50% saturated ammonium sulfate . We also studied the ability of LALF to neutralize LPS . LPS preincubated with LALF was less mitogenic for murine splenocytes, was less pyrogenic in the rabbit fever assay, was less lethal in mice which had been sensitized to LPS with actinomycin D, and induced less fever, neutropenia, and pulmonary hypertension when infused into sheep . Our findings extend prior studies which suggested that LALF binds to and neutralizes LPS from multiple strains of gram-negative bacteria. Infect Immun, 1992 Jun, 60(6), 2281 - 7 Intracellular growth of Afipia felis, a putative etiologic agent of cat scratch disease; Birkness KA et al.; The organism Afipia felis, which is though to be an etiologic agent of cat scratch disease, is a gram-negative rod that is clearly seen in infected tissue but is very difficult to isolate from clinical specimens; there has been only one report to date of the successful isolation and maintenance of the bacterium on artificial medium . We have found that A . felis will attach, invade via phagocytosis, and multiply intracellularly within the phagosomes of primary human monocytes and HeLa cells . Once in the cell, the bacterium appears to change morphologically, becoming longer and more pleomorphic, and loses its ability to grow on an artificial medium . Unique proteins have been identified in both the intra- and extracellular variants of A . felis . Convalescent-phase sera from patients with cat scratch disease react poorly with intracellular and extracellular bacteria, suggesting a poor humoral response . The tissue culture protocol presented has been used to isolate 14 new strains of A . felis and has for the first time permitted study of the pathogenesis of this unique organism. J Infect Dis, 1992 Jun, 165(6), 1138 - 41 Interactions between live Bartonella bacilliformis and endothelial cells; Garcia FU et al.; Bartonella bacilliformis, a gram-negative, flagellated, motile bacterium, is the etiologic agent of verruca peruana . It is found within the verruca, where it can form large cytoplasmic (Rocha-Lima) inclusions in endothelial cells . Previously, an activity has been described in homogenates of B . bacilliformis that in vitro increases the proliferation of endothelial cells and their production of tissue-type plasminogen activator (t-PA) and in vivo is angiogenic . The aim of the present study was to determine if live B . bacilliformis similarly stimulated endothelial cells and produced the Rocha-Lima inclusion . By measuring proliferation of cells and the production of t-PA in vitro, it was found that the live bacteria increased both parameters in a fashion similar to the homogenates of B . bacilliformis . Interaction between the bacteria and endothelial cells appeared to be necessary for proliferation . On electron microscopy, bacteria penetrated the endothelial cell within 1 h, forming a small membrane-bound inclusion . By 12 h, a large membrane-bound inclusion, similar to the Rocha-Lima inclusion, containing numerous bacteria was present . These data provide further evidence that B . bacilliformis has an angiogenic activity and that the bacteria are at least in part responsible for the vascular proliferation of the verruca. Circ Shock, 1992 Jun, 37(2), 164 - 8 Differential contractile responses of mesenteric and pulmonary artery segments to norepinephrine and phorbol ester in the septic pig; Suba EA et al.; The contractile response of isolated vascular segments was studied in Yucatan miniature swine approximately 48 hr after induction of sepsis by intraperitoneal injection of live Escherichia coli . Compared to non-septic controls, segments of the cranial mesenteric artery from septic animals showed a significantly attenuated contractile response to the adrenergic receptor agonist norepinephrine (NE) . The EC50 for NE increased from 1.1 +/- 0.3 to 6.3 +/- 2.0 microM and the Emax decreased from 1,010 +/- 179 to 387 +/- 75 mg tension/mg tissue . In contrast, segments of the pulmonary artery showed no significant difference in contractility to NE between sham-operated and septic animals . Mesenteric and pulmonary artery segments from both septic and control animals exhibited similar contraction to the protein kinase C activator phorbol-12, 13-dibutyrate . This suggests that the observed hyporeactivity to NE in porcine mesenteric artery segments is not simply due to cellular damage by toxins associated with the septic state . The results also indicate that the impact of gram-negative sepsis on vascular contractile function varies between tissue from the systemic and pulmonary circulation in pigs. Circ Shock, 1992 Jun, 37(2), 111 - 6 Protein kinase C activity and lipogenesis from glucose in isolated adipocytes of endotoxemic rats; Spitzer JA et al.; The hypothesis was tested that the insulin-like effects of Gram-negative bacterial endotoxins (ET), exerted after in vivo administration on subsequently isolated adipocytes, might be associated with changes in protein kinase C (PKC) activity . The latter is believed to be involved in insulin's mechanism of action on adipocytes . E . coli ET was administered to rats either as a bolus injection (1 mg/100 g bw, in 160-180 g rats, LD50 for 6 hr) or via subcutaneously implanted osmotic pumps (0.1 mg/100 g bw/24 hr, for 30 hr, in 340-380 g rats) . Control animals received sterile saline . At 6 hr after bolus injection, and at 30 hr after the onset of ET infusion, the animals were sacrificed and epididymal adipocytes isolated . PKC activity and intracellular distribution were assayed after partial purification on DE-52 cellulose minicolumns . Lipogenesis was measured by {3-3H}-D-glucose incorporation into triglyceride . ET treatment by either mode induced a significant increase (76-80%) in PKC activity . PKC intracellular distribution was altered only in chronically ET-treated rats and was expressed as an increased enzyme activity in the membrane fraction . The increased PKC activity was associated with elevated rates of insulin-stimulated lipogenesis only in young rats . We conclude that in young rats, whose adipocytes display high rates of lipogenesis along with elevated insulin sensitivity, PKC is likely to be one of the possible factors involved in mediation of insulin-like effects of ET. Eur J Immunol, 1992 Jun, 22(6), 1663 - 5 Lipopolysaccharide induces up-regulation of CD14 molecule on monocytes in human whole blood; Marchant A et al.; We examined by flow cytometry the expression of lipopolysaccharide (LPS) receptor CD14 molecule on monocytes after addition of LPS to human whole blood . Within 30 min LPS induced an increase in monocyte CD14 expression, peaking between 1 and 3 h and followed by a slow decrease . Maximal increase in anti-CD14 monoclonal antibody binding sites was estimated as twofold the basal value . This effect, already observed with very low concentrations of LPS (10 pg/ml), was dose dependent . Protein synthesis was not involved in the CD14 hyperexpression since it was not influenced by co-incubation with cycloheximide . Finally, LPS-induced up-regulation of monocyte CD14 was associated with an increased binding of fluoresceinated LPS . We conclude that LPS in whole blood up-regulates the expression of its own CD14 receptor on monocytes, a phenomenon that could be relevant to the pathogenesis of gram-negative sepsis. Res Microbiol, 1992 Jun, 143(5), 471 - 9 Transposon mutagenesis in Legionella pneumophila . I.--Persistence of suicide and broad host-range plasmids; Tully M et al.; Two of three highly virulent strains of Legionella pneumophila could act as recipients at high frequencies in conjugation experiments with Escherichia coli donor strains carrying broad host-range plasmids belonging to incompatibility groups N, P and W . All broad host-range and most transposon-delivery plasmids persisted within transconjugants with high stability . Only one (pSUP1021) of several vehicles designed for the delivery of transposons into the chromosome of Gram-negative bacteria was found to yield transposon mutants of Legionella at a detectable frequency. Ann Hematol, 1992 Jun, 64 Suppl, A158 - 61 Prevention and treatment of CMV infection after allogeneic bone marrow transplant; Gluckman E et al.; CMV infection is the major infectious complication following bone marrow transplantation . It is most often related to reactivation of latent infection in patients who were CMV seropositive before BMT . The incidence and severity have recently been modified by the use of preventive and curative treatments . Prevention of CMV infection with the transfusion of seronegative blood products is useful only when donor and recipient are seronegative . High-dose acyclovir has been shown effective in one randomized study . A multicenter study is currently being performed in Europe to confirm this result . Intravenous gammaglobulins seemed to lower the number of patients who incur interstitial pneumonitis but not the incidence of viremia . They also decreased the incidence of gram-negative sepsis and severe GVH and improved survival . The treatment is based on the use of gancyclovir . Several studies show that gancyclovir is more effective in asymptomatic patients with viral isolation from blood or bronchoalveolar lavage . The addition to gancyclovir of high-dose gammaglobulin improves survival in symptomatic patients with interstitial pneumonitis . This progress in the prevention and treatment of CMV infection has improved the overall results of allogeneic bone marrow transplantation. Cytokine, 1992 May, 4(3), 205 - 13 Oxidative tryptophan metabolism in renal allograft recipients: increased kynurenine synthesis is associated with inflammation and OKT3 therapy; Holmes EW et al.; Serum concentrations of tryptophan (TRP) and kynurenine (KYN) were determined in renal allograft recipients (RAR) as an index of interferon-gamma-induced, indoleamine-dioxygenase-catalysed TRP degradation . Serum TRP and KYN in RAR during periods of stable graft function were typically within the normal range, however, the median values for serum KYN demonstrated significant increases 5-7 days prior to biopsy-confirmed acute rejection (1.6-fold, P less than 0.01) and on the day of biopsy (1.7-fold, P less than 0.001) . Serum KYN was also markedly elevated in patients who contracted viral or Gram-negative bacterial infections in the absence of graft rejection . Serum KYN was not correlated with serum creatinine in RAR nor were serum TRP or KYN affected by antirejection therapy with high dose steroids . Retrospective analysis of intra-patient changes in serum KYN demonstrated that KYN monitoring was a useful adjunct to serum creatinine in the early detection of first acute rejection episodes . The first course of OKT3 therapy was associated with low serum TRP and significant increases in serum KYN (two- to three-fold) following the first three doses . The time course of these abnormalities corresponded to that over which many of the side effects of the OKT3 'first dose reaction' have been reported to occur . Significant changes in serum KYN were not observed in patients receiving repeat courses of OKT3 therapy . Significant decreases in serum TRP and significant increases in serum KYN were both prevalent and frequent in RAR during the first two postoperative months.(ABSTRACT TRUNCATED AT 250 WORDS) Br J Anaesth, 1992 May, 68(5), 499 - 502 Gastroduodenal dysfunction as a cause of gastric bacterial overgrowth in patients undergoing mechanical ventilation of the lungs; Inglis TJ et al.; We have studied 15 patients undergoing mechanical ventilation of the lungs for evidence of a relationship between gastroduodenal dysfunction and gastric bacterial overgrowth . Duodenal reflux was detected by quantitative measurement of conjugated bilirubin in gastric aspirate specimens . The pH and bacterial content of these specimens were analysed . A minority of specimens with pH less than 3.5 contained measurable numbers of viable bacteria . The total bacterial count and the count of Gram negative bacteria correlated significantly with specimen pH in both cases (P less than 0.001, in both) . In the 72 specimens of gastric aspirate with pH greater than 3.5, the presence of Gram negative bacteria was associated significantly with detectable bilirubin (P less than 0.001) . The total bacterial count was greater also in specimens containing bilirubin (P = 0.009) . These results suggest that gastroduodenal dysfunction may promote gastric bacterial overgrowth, contributing to the development of ventilator-associated pneumonia. Klin Monatsbl Augenheilkd, 1992 May, 200(5), 519 - 21 {Acute anterior uveitis: para-infectious hypothesis in predisposed individuals}; Andenmatten R et al.; The etiology and the physiopathology of acute anterior uveitis (AAU) is not well understood yet . However, two major predisposing factors have been identified: a bacterial infection especially with gram negative organisms (functioning as a trigger) and a genetic background, in particular the expression of HLA B-27 tissue antigen . We report the case of a young woman returning from travel to the Far East with her partner . Both presented simultaneously a gastrointestinal infection with fever and diarrhea . Despite extensive investigations, the infectious agent was never identified because of early empirical antibiotic therapy . A few days later, the patient developed AAU of a moderate grade in both eyes . HLA B-27 testing was positive for her, but not for her partner . Experimental research, based on a animal model such as endotoxin-induced uveitis (EIU), gives us some insight into the possible pathogenic mechanisms of AAU . Footpad injection of endotoxin (lipopolysaccharide component of the wall of gram negative), produce an acute anterior uveitis in rats . Extensive histologic analysis of other organs shows that the anterior segment of the eye is the only structure involved . Intensity of inflammation varies in different rat strains, stressing the importance of the genetic background . The similarity of the animal model to AAU will contribute to orient clinical research towards identifying more thoroughly the possible infectious agent at the origin of AAU and possibly to develop a prophylactic therapy. Childs Nerv Syst, 1992 May, 8(3), 139 - 41 The probable role of hydrocephalus in the development of intraventricular septa . An observation of one case; Lazareff JA et al.; Multiloculated cerebral ventricles are a well-known complication of neonatal meningitis secondary to gram-negative bacteria . Their presence often hampers the proper functioning of the multiple shunts required for draining the ventricles . To determine whether the associated hydrocephalus may contribute to the development of the ventricular septa, we analyzed the histological structure of the ventricular wall and of the ventricular septa of a child who died as a consequence of Escherichia coli meningitis and unilateral hydrocephalus . Our results show that the ventricular septa are formed by glial protrusion into the ventricles . The ependymal wall of the grossly dilated ventricle was disrupted, but not that of the contralateral ventricle . We hypothesize that the presence of an insufficiently controlled hydrocephalus may have been one of the factors that induced the formation of the septa . It is suggested that an external ventricular derivation should be used during the active phase of the infection. Clin Infect Dis, 1992 May, 14(5), 1089 - 99 beta-Lactamases of gram-negative bacteria: new challenges for new drugs; Sanders CC; The major emphasis in new drug design within the beta-lactam family has been on compounds less susceptible to hydrolysis by beta-lactamases and on combinations containing an enzyme-labile drug plus a beta-lactamase inhibitor . The introduction of such new compounds into clinical use has been followed by the discovery of novel mechanisms of resistance among gram-negative bacteria . These include the appearance of new enzymes, many of which are derivatives of older beta-lactamases . In addition, genes for certain broad-spectrum enzymes previously restricted to chromosomal sites have moved onto plasmids . There is now a greater appreciation of how alterations in enzyme expression--either alone or in concert with changes in drug permeation--can also lead to resistance . Clearly, recent events in the development of new beta-lactam agents have led to a new phase in the understanding of beta-lactam resistance. Optom Vis Sci, 1992 May, 69(5), 354 - 7 Conjunctival flora in extended wear of rigid gas permeable contact lenses; Fleiszig SM et al.; A longitudinal study was performed to examine the effect of rigid gas permeable (RGP) contact lenses (Boston Equalens II and Quantum II) on the conjunctival flora of 45 young healthy subjects . Microbial flora were determined before delivery of lenses . Subjects wore lenses on an extended wear basis, removing them every 7 days for cleaning and disinfection . Cultures were repeated after 2 months of lens wear and the microbial flora were found to be significantly altered compared to the prelens wear results (0.05 greater than p greater than 0.02) . Changes to conjunctival flora included an increase in the number of eyes from which potentially pathogenic microorganisms were isolated, an increase in the number of eyes that were culture-negative, and a decrease in the number of eyes harboring only normal conjunctival flora . The increase in potentially pathogenic flora was not specific for Gram-negative bacteria, which are most often associated with infectious keratitis during contact lens wear. J Trauma, 1992 May, 32(5), 564 - 9 Intra-abdominal sepsis and adrenergic receptor response; Forse RA et al.; This study measured the adrenergic receptor response of 13 patients with severe intra-abdominal sepsis, who required laparotomy and an open abdominal closure with Marlex mesh . The source of the sepsis was gram-negative organisms of intestinal origin . There were seven survivors and six nonsurvivors . When the patients were stratified into survivors and nonsurvivors, the Septic Severity Score, the APACHE II score, the Acute Physiological Score, and the Glasgow Coma Scale score results were not significantly different between groups . The alpha-2 and beta-1 adrenergic receptor responses were measured in the adipose tissue of the abdominal wall and the small bowel mesentery on day 1 of admission to the intensive care unit . The results demonstrated that the alpha-2 and beta-1 receptors of the nonsurvivors had a significantly decreased receptor response with desensitization and down regulation . The alpha-2 and beta-1 receptors of the survivors had an increased response with hypersensitization and up regulation . This study indicates that the adrenergic receptor pattern is distinctly different between survivors and nonsurvivors with severe abdominal gram-negative sepsis . The pattern differences occurred early (within 24 hours) when the patients had similar physiologic profiles . It is concluded that adrenergic receptor response may be a biologic indicator of the magnitude of the septic injury and a predictor of outcome. Clin Pediatr (Phila), 1992 May, 31(5), 295 - 8 A comparison of silver nitrate with erythromycin for prophylaxis against ophthalmia neonatorum; Zanoni D et al.; Although prophylactic eyedrops to treat ophthalmia neonatorum is mandated nationwide, states and hospitals are free to choose specific drugs . To compare two of these agents, we studied the incidence and characteristics of ophthalmia neonatorum in two UCLA teaching hospitals over a five-year period . One, which used 1% silver nitrate solution exclusively, had 50 cases in 34,772 births, a frequency of 0.14% . The other used 0.5% erythromycin ointment exclusively and had 43 cases in 12,652 births, a frequency of 0.34% . Ophthalmia neonatorum was more frequent in the hospital using erythromycin (p less than 0.001), as was chlamydial conjunctivitis (p less than 0.02) . Although not statistically significant, gonococcal conjunctivitis was found in four infants, all in the hospital using silver nitrate . Because silver nitrate was found more effective in decreasing the total frequency of all cases of ophthalmia neonatorum, and cases caused by Chlamydia and gram-negative bacteria specifically, this drug still should be considered as a primary prophylactic agent against ophthalmia neonatorum. Infect Immun, 1992 May, 60(5), 1946 - 51 Identification and purification of a cpn60 heat shock protein homolog from Helicobacter pylori; Dunn BE et al.; Helicobacter pylori is associated with gastritis and peptic ulcer disease in humans . We have identified a homolog of the chaperonin cpn60 family of heat shock proteins in H . pylori, referred to as Hp54K . Hp54K, purified from water-extractable H . pylori proteins, migrated as a single band at 54 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis . Its native molecular mass was 740 kDa; thus, Hp54K apparently comprises a 14-mer . The N-terminal 33 residues of Hp54K exhibited 60.6, 57.6, 54.5, 54.5, 51.5, and 51.5% identity with corresponding sequences in the following cpn60 homologs: HtpB (Legionella pneumophila), P1 (human mitochondria), GroEL (Escherichia coli), BA60K (Brucella abortus), HypB (Chlamydia trachomatis), and the 65-kDa immunodominant protein of Mycobacterium bovis BCG, respectively . Hp54K was the only protein recognized in whole-cell preparations of H . pylori by immunoblotting using monospecific antisera against cpn60 homologs from L . pneumophila, E . coli, C . trachomatis, and M . bovis BCG . Antiserum against Hp54K recognized proteins with molecular masses of 50 to 60 kDa in a large number of gram-negative bacteria, consistent with the known highly conserved nature of cpn60 proteins . Hp54K is a major protein and is immunogenic in humans infected with H . pylori . Thus, Hp54K shares many similarities with known cpn60 homologs . On the basis of the proposed role of other cpn60 proteins in induction of chronic inflammation, immune cross-reactivity between Hp54K and gastric tissue may provide an important link between H . pylori infection and gastritis. Infect Immun, 1992 May, 60(5), 1756 - 60 Effects of endotoxin-associated protein on hematopoiesis; Porat R et al.; Endotoxin-associated protein (EAP), a gram-negative bacterial cell wall component, was evaluated for its effects on hematopoietic colony formation in vitro . Colony-stimulating activity, induced by EAP on circulating and bone marrow progenitor cells, was found to be partially mediated by T cells and augmented by interleukin-3 . The addition of anti-human interleukin-1 (IL-1) antibodies reduced EAP activity, suggesting that EAP may induce IL-1 production . However, EAP was shown to promote the growth of mature progenitor cells independently, unlike the effects of IL-1 on the hematopoietic system . These studies demonstrate that bacterial components other than lipopolysaccharide, such as EAP, may have hematopoietic activity. Proc Natl Acad Sci U S A, 1992 May 1, 89(9), 4076 - 80 Coordinated antiinflammatory effects of interleukin 4: interleukin 4 suppresses interleukin 1 production but up-regulates gene expression and synthesis of interleukin 1 receptor antagonist; Vannier E et al.; Interleukin 1 receptor antagonist (IL-1ra), a naturally occurring polypeptide with amino acid sequence homology to interleukin 1 alpha (IL-1 alpha) and interleukin 1 beta (IL-1 beta), prevents Escherichia coli-induced shock and death . Both IL-1 and IL-1ra are produced by monocytes stimulated with lipopolysaccharide (LPS) . Because interleukin 4 (IL-4) suppresses IL-1 production, we investigated whether IL-4 modulated IL-1ra synthesis in LPS-stimulated human peripheral blood mononuclear cells . IL-1 beta and IL-1ra were measured by specific RIAs . IL-4 alone (0.01-100 ng/ml) did not stimulate IL-1 beta synthesis but rather induced IL-1ra (4.82 +/- 0.94 ng/ml) . LPS induced synthesis of both IL-1 beta (6.67 +/- 1.06 ng/ml) and IL-1ra (10.77 +/- 2.79 ng/ml) . IL-4 suppressed LPS-induced IL-1 beta mRNA accumulation and synthesis . However, IL-4 acted synergistically with LPS in inducing IL-1ra . IL-4 enhanced LPS-induced IL-1ra mRNA accumulation 4-fold and IL-1ra protein synthesis nearly 2-fold . Moreover, IL-1ra mRNA levels were maximal after 6 hr of exposure to LPS but peaked within the first 3 hr in the presence of IL-4 . IL-4 added as late as 12 hr after LPS stimulation still enhanced IL-1ra synthesis . In human peripheral blood mononuclear cells stimulated with IL-1 alpha, IL-4 markedly suppressed IL-1 beta production but enhanced IL-1ra synthesis greater than 2-fold . Because IL-4 favors synthesis of the natural antagonist IL-1ra over synthesis of the agonist IL-1, IL-4 may exert potent antiinflammatory effects on host responses to Gram-negative infections. J Clin Invest, 1992 May, 89(5), 1551 - 7 Interleukin-1 receptor blockade improves survival and hemodynamic performance in Escherichia coli septic shock, but fails to alter host responses to sublethal endotoxemia; Fischer E et al.; The present study was undertaken to evaluate the extent to which an endogenous interleukin-1 (IL-1) response contributes to the hemodynamic and metabolic consequences of sublethal endotoxemia or lethal Gram-negative septic shock . Young, healthy baboons received either a sublethal dose of lipopolysaccharide (LPS) or an LD100 of