J Infect Dis, 1999 Feb, 179(2), 508 - 12 The role of bacterial lipopolysaccharide-bound neutrophils in the pathogenesis of Kawasaki disease; Takeshita S et al.; To investigate the possible role of lipopolysaccharide (LPS, endotoxin) in the pathogenesis of Kawasaki disease, neutrophils from 15 patients with the disease and 7 with sepsis (4 infected with gram-negative bacteria and 3 with gram-positive bacteria) were analyzed by flow cytometry using anti-LPS and anti-CD14 monoclonal antibodies . The number of LPS- and CD14-positive neutrophils was dramatically higher early after the onset of Kawasaki disease and gram-negative sepsis but not with gram-positive sepsis . An immunoprecipitation analysis revealed LPS was bound to CD14 in vivo on neutrophils from Kawasaki disease patients . The mean plasma level of neutrophil elastase was significantly higher in the acute phase of Kawasaki disease than in the acute phase of sepsis . These findings suggest that exposure to LPS occurs at the onset of Kawasaki disease when LPS-bound neutrophils secrete excess protease (implicated in neutrophil-mediated endothelial injury) into the circulation. J Pharm Pharmacol, 1998 Nov, 50(11), 1255 - 60 The kinetic profile of vancomycin in neonates; Silva R et al.; The pharmacokinetic parameters of vancomycin in a neonatal population have been characterized to enable development of optimum dosage guidelines for neonatal intensive-care units and to examine the relationship between these pharmacokinetic parameters and various demographic, developmental and clinical factors which might be associated with changes in the kinetic profile of vancomycin . Forty-four infants (twenty-five males and nineteen females) with suspected or proven Gram-positive infection and who received intravenous vancomycin between October 1993 and December 1996 were included in this retrospective analysis . Gestational age ranged from 25 to 40 weeks and postconceptional age at the time of the study ranged from 28 to 45 weeks . Sixty case-studies were obtained from the forty-four patients, with one period of study corresponding to one week or one cycle of therapy . Vancomycin pharmacokinetic parameters were determined by use of a one-compartment model . By regression analysis the current weight (g) was shown to be the stronger covariate, and both vancomycin clearance (L h(-1)) and volume of distribution (L) had to be normalized . The vancomycin volume of distribution depended on the postconceptional age with a cut-off at 32 weeks, whereas vancomycin clearance depended on the presence or absence of concomitant treatment with indomethacin or of mechanical ventilation, or both . On the basis of the pharmacokinetic parameters obtained we suggest initial dosage guidelines for vancomycin ranging from 10 mg kg(-1) every 8 h to 10 mg kg(-1) every 12 h, depending on the demographic and clinical characteristics of the patients . The results obtained enabled application of better a priori and a posteriori dosage schedules to infants in neonatal intensive-care units by use of the Bayesian approach, although further prospective study is recommended before direct extrapolation to patients in other settings. Crit Care Med, 1998 Dec, 26(12), 2078 - 86 Has the mortality of septic shock changed with time; Friedman G et al.; OBJECTIVES: To determine whether a systematic review of the literature could identify changes in the mortality of septic shock over time . DATA SOURCES: A review of all relevant papers from 1958 to August 1997, identified through a MEDLINE search and from the bibliographies of articles identified . DATA SYNTHESIS: The search identified 131 studies (99 prospective and 32 retrospective) involving a total of 10,694 patients . The patients' mean age was 57 yrs with no change over time . The overall mortality rate in the 131 studies was 49.7% . There was an overall significant trend of decreased mortality over the period studied (r=.49, p < .05) . The mortality rate in those patients with bacteremia as an entry criterion was greater than that rate in patients whose entry criterion was sepsis without definite bacteremia (52.1% vs . 49.1%; chi2=6.1 and p< .05) . The site of infection altered noticeably over the years . Chest-related infections increased over time, with Gram-negative infections becoming proportionately less common . If all other organisms and mixed infections are included with the Gram-positives, the result is more dramatic, with these organisms being causative in just 10% of infections between 1958 and 1979 but in 31% of infections between 1980 and 1997 . CONCLUSIONS: The present review showed a slight reduction in mortality from septic shock over the years, although this result should be approached with caution . The heterogeneity of the articles and absence of a severity score for most of the studies limited our analysis . Furthermore, there was an increasing prevalence of Gram-positive causative organisms, and a change of the predominant origin of sepsis from the abdomen to the chest. Int J Pancreatol, 1998 Dec, 24(3), 187 - 91 Difference in microbes contaminating pancreatic necrosis in biliary and alcoholic pancreatitis; Raty S et al.; CONCLUSION: There are differences in the microbiology of infected pancreatic necrosis in alcoholic and biliary pancreatitis . One possible explanation may be different routes of contamination . BACKGROUND: Infection is a severe complication in acute pancreatitis . Bacteria are found in 40-70% of all patients suffering from necrotizing pancreatitis . We investigated whether there were any differences in microbes isolated from pancreatic necrosis in biliary and alcoholic pancreatitis . METHODS: Microbiological tests were conducted on necrosis taken at the operation for pancreatitis with the etiology of (group A) alcoholic pancreatitis (n = 47) and (group B) biliary pancreatitis (n = 23) . Patients with simultaneous cholecystitis were excluded . The time from the first symptoms to the operation or the extent of necrosis did not differ between the groups . RESULTS: Microbes were isolated more often in the cultures from group B than group A (17/23 = 74% vs 15/47 = 32%, p = 0.001) . The most common were Gram-positive bacteria in group A and Gram-negative bacteria in group B . From the first week, from the onset of symptoms to the operation . Gram-negative bacteria were isolated significantly more often in the cultures from group B patients than from group A patients (8/10 = 80% vs 1/5 = 20%, p = 0.04) . In multivariate analysis, we found that biliary pancreatitis was an independent risk factor (adds ratio 5.5, 95% confidence interval {CI} 0.59-52.10) of contamination of necrosis with Gram-negative bacteria. Bioorg Med Chem Lett, 1998 Aug 18, 8(16), 2093 - 8 Antineoplastic agents . 397: Isolation and structure of sesterstatins 4 and 5 from Hyrtios erecta (the Republic of Maldives); Pettit GR et al.; The wide ranging marine sponge Hyrtios erecta is the source of the spongistatins, a new class of macrocyclic lactone antineoplastic agents . Continuation of a detailed investigation of cancer cell growth inhibitory (P388 lymphocytic leukemia) fractions (trace) from H . erecta has revealed the presence (10(-5) to 10(-7)% yield) of cytotoxic pentacyclic sesterterpenes . Employing P388 leukemia and human tumor cell line-guided bioassay techniques, two new moderate inhibitors of cancer cells were isolated and named sesterstatins 4 (1a, P388 ED50 4.9 micrograms/mL) and 5 (1b, DU-145 prostate GI50 1.9 micrograms/mL) . Similar to other sesterterpenes, sesterstatin 5 inhibited growth of a Gram-positive bacterium . High field (500 MHz) 2-D NMR techniques were primarily employed for initial structural assignments, and structural assignments were confirmed by X-ray crystal structure determination of sesterstatin 4 (1a) and 5 (1b). Bioorg Med Chem Lett, 1998 Jul 21, 8(14), 1897 - 902 Discovery of a novel benzyloxyisoquinoline derivative with potent anti-Helicobacter pylori activity; Yoshida Y et al.; The synthesis and in vitro optimization of the anti-Helicobacter pylori activity of a novel series of benzyloxyisoquinoline derivatives discovered by a random screening process, are described . FR180102 (7f), having a 3-acetamido-2,6-dichlorobenzyl moiety, was found to have extremely potent activity against H . pylori and no effect against a series of common Gram-positive and Gram-negative bacteria. Naturwissenschaften, 1998 Dec, 85(12), 583 - 92 Coupling physiology and gene regulation in bacteria: the phosphotransferase sugar uptake system delivers the signals; Stulke J et al.; In many bacteria a crucial link between metabolism and regulation of catabolic genes is based on the phosphotransferase sugar uptake system (PTS) . We summarize the mechanisms of the signaling pathways originating from PTS and leading to regulation of transcription . A protein domain, called PTS regulation domain (PRD), is linked to many antiterminators and transcriptional activators and regulates their activity depending on its state of phosphorylation . Two sites can be phosphorylated in most PRDs: HPr-dependent modification at one site leads to activation while enzyme II dependent phosphorylation of the other site renders it inactive . In addition, PTS components are used to generate cofactors for regulators of transcription . The paradigm is the enzyme II dependent activity of adenylate cyclase determining the cyclic AMP level in Escherichia coli and thereby the activity of the catabolite activator protein . In many gram-positive bacteria catabolite repression is mediated by the catabolite control protein CcpA, which requires HPr Ser-46 phosphate as a cofactor to regulate transcription of catabolic genes . HPr Ser-46 phosphate is produced by HPr kinase, the activity of which is under metabolic control via the concentrations of glycolytic intermediates . These recent results establish a multifaceted regulatory role for PTS in addition to its well-established function in active sugar uptake. J Ocul Pharmacol Ther, 1998 Dec, 14(6), 575 - 83 Ocular penetration of oral clarithromycin in humans; Al-Sibai MB et al.; Clarithromycin has a wide spectrum of activity against many gram-positive and gram-negative organisms, intracellular pathogens, and opportunistic pathogens . To examine the penetration of clarithromycin in the ocular tissues, 21 patients who underwent elective cataract surgery (Group I) received a single 500-mg dose of clarithromycin orally either 4, 8, 10, 12, or 22 hours before cataract surgery, and 21 patients who underwent elective retina/vitreous surgery (Group II) received 500 mg every 12 hours orally for 3 days before the surgery with the last dose given either 3, 6, 8, 11, or 24 hours before the surgery . Serum from all patients was assayed for clarithromycin prior to drug administration and at the time ocular specimen was taken . Aqueous, iris, and vitreous samples were also assayed for clarithromycin concentration . The concentrations of clarithromycin in the aqueous fluid 4, 8, 10, 12, and 22 hours after administration were: (mean +/- SD) 0.13+/-0.05, 0.137+/-0.11, 0.074+/-0.03, 0.06+/-0.02, and 0.074+/-0.04 microg/ml, respectively . Concentration of clarithromycin in vitreous 3, 6, 8, 11, and 24 hours after administration were: (mean +/- SD) 0.11+/-0.02, 0.257+/-0.13, 0.27+/-0.21, 0.307+/-0.26 and 0.108+/-0.07 microg/ml, respectively . The mean concentration of clarithromycin in the iris was 6.2 microg/g . In conclusion, this data suggest that clarithromycin widely penetrates and adequately concentrates in the aqueous humor, vitreous humor, and iris tissue after oral administration and therefore is effective in the management of many infectious ocular conditions. Proc Natl Acad Sci U S A, 1998 Dec 22, 95(26), 15469 - 74 Biosynthesis of the Pseudomonas polyketide coronafacic acid requires monofunctional and multifunctional polyketide synthase proteins; Rangaswamy V et al.; Coronafacic acid (CFA) is the polyketide component of the phytotoxin coronatine, a virulence factor of the plant pathogen Pseudomonas syringae . Our current knowledge of polyketide biosynthesis largely is based on the analysis of polyketide synthases (PKSs) in actinomycetes and other Gram-positive bacteria . Consequently, the cloning and characterization of the CFA biosynthetic gene cluster will contribute significantly to our knowledge of polyketide synthesis in Pseudomonas . In this report, we describe two genes in the CFA biosynthetic gene cluster that encode PKSs that are structurally and functionally similar to the multifunctional modular PKSs, which catalyze the synthesis of macrolide antibiotics . The CFA PKS genes were overproduced in Escherichia coli and shown to cross-react with antisera made to a modular PKS involved in erythromycin synthesis . A scheme for CFA biosynthesis is presented that incorporates the activities of all proteins in the CFA PKS . In this report a gene cluster encoding a pseudomonad polyketide has been completely sequenced and the deduced gene functions have been used to develop a biosynthetic scheme. J Clin Gastroenterol, 1998 Dec, 27(4), 342 - 5 Extremely high levels of alkaline phosphatase in hospitalized patients; Maldonado O et al.; We determined the diseases associated with extremely high levels of alkaline phosphatase in hospitalized patients . Computerized laboratory records of the Hospital of Saint Raphael identified all inpatients who had elevations of alkaline phosphatase above 1,000 U/l from April 1994 to September 1995 . Thirty-seven inpatients with alkaline phosphatase levels above 1,000 U/l were identified . Six had bone involvement from malignancy or Paget's disease and were eliminated from further analysis, and 31 patients were included in the study . Levels of alkaline phosphatase ranged from 1,014 to 3,360 U/l . Ten patients had sepsis as the cause of the elevated alkaline phosphatase . These included gram-negative organisms, gram-positive organisms, and two patients with fungal sepsis . Seven of 10 patients with sepsis had an extremely high alkaline phosphatase level and a normal bilirubin, 3 of 10 patients with sepsis also had acquired immunodeficiency syndrome (AIDS) . Eight patients had biliary obstruction, 7 with malignant obstruction and 1 with a common bile duct stone . Nine patients had AIDS . The cause of the elevated alkaline phosphatase in these included three with sepsis, three with mycobacterium avium intracellulare (MAI) infection, two with cytomegalovirus infection, and one with Dilantin toxicity . Three patients had diffuse liver metastases . Finally, four patients had benign intrahepatic disease, including one patient with liver hemangiomas, one patient with sarcoid hepatitis, one patient with lead toxicity, and one patient with drug-induced cholestasis . Extremely high elevations of alkaline phosphatase are most frequently seen in patients with sepsis, malignant obstruction, and AIDS . Patients with sepsis can have an extremely high alkaline phosphatase level and a normal bilirubin . A variety of other causes were also noted. Anal Chem, 1998 Dec 1, 70(23), 4890 - 5 Applications of 1.06-micron IR laser desorption on a Fourier transform mass spectrometer; Ho YP et al.; Various sugars, peptides, and lipids were analyzed on a Fourier transform mass spectrometer using laser desorption and ionization with and without the assistance of matrixes . A compact Nd:YAG laser with an output at 1.06 microns corresponding to fundamental frequency was employed . Gram-negative and Gram-positive bacteria were also subjected to laser desorption mass spectrometry . Characteristics ions of conjugated lipid, formed by attachment of alkali metal cations, endogenous to the cells, were observed . Particle/liquid matrixes (e.g., cobalt in glycerol) proved to be useful with the 1.06-micron laser . The particles absorb efficiently laser radiation in a broad wavelength range . The liquid provides the same advantages as in fast atom bombardment: increased signal-to-noise ratios and enhanced sample lifetimes . The effect of laser power on total ion current was shown to differ for samples with and without the particle/liquid matrix . The Fourier transform analyzer provides MS/MS capability for both positive and negative ions from complex mixtures . Ions desorbed externally are introduced into the cell via a quadrupole ion guide with a lower mass cutoff . Such a setup allows matrix ions to be excluded and thus provides excellent signal-to-noise ratios for lower mass range fragment ions formed inside the cell. Int J Mol Med, 1998 Feb, 1(2), 387 - 97 Gram-negative and gram-positive bacterial products induce differential cytokine profiles in the brain: analysis using an integrative molecular-behavioral in vivo model; Plata-Salaman CR et al.; Bacterial-derived products {e.g., lipopolysaccharide (LPS) from Gram-negative and muramyl dipeptide (MDP) from Gram-positive bacteria} are proposed to play a pivotal role in the generation of neurological and neuroinflammatory/immunological responses during bacterial infections of the nervous system . LPS and MDP may act through cytokines; cytokine-neuropeptide interactions may also be involved . Here, we investigated cytokine and neuropeptide mRNA profiles in specific brain regions in response to the intracerebroventricular administration of LPS and MDP . IL-beta1 system components (ligand, signalling receptor, receptor accessory proteins, receptor antagonist), TNF-alpha, TGF-beta1, glycoprotein 130 (IL-6 receptor signal transducer), OB protein (leptin) receptor, neuropeptide Y, Y5 receptor, and pro-opiomelanocortin (opioid peptide precursor) mRNAs were analyzed . The same brain region sample was assayed for all components . LPS and MDP administration induced significantly different behavioral and molecular profiles . LPS was significantly more potent than MDP in inducing anorexia and in up-regulating pro-inflammatory cytokines (IL- beta1 and TNF-alpha mRNAs in the cerebellum, hippocampus and hypothalamus; MDP was more potent in up-regulating anti-inflammatory cytokine (IL-1 receptor antagonist and TGF-beta1) mRNAs . LPS and MDP also modulated hypothalamic IL-1 receptor mRNA components, but did not affect any of the neuropeptide-related components examined . The results suggest that the magnitude of neurological manifestations induced by LPS and MDP may involve the ratio between stimulatory and inhibitory cytokines, and this ratio may have implications for the neuroinflammatory/neurotoxic events associated with bacterial infections of the central nervous system. FEBS Lett, 1998 Nov 13, 439(1-2), 192 - 6 Identification and subcellular localization of a novel Cu,Zn superoxide dismutase of Mycobacterium tuberculosis; Wu CH et al.; Periplasmic copper, zinc superoxide dismutases (Cu,ZnSOD) of several Gram-negative pathogens have been shown to play an important role in protection against exogenous superoxide radicals and in determining virulence of the pathogens . Here we report the cloning and characterization of the sodC gene, encoding Cu,ZnSOD, from the Gram-positive Mycobacterium tuberculosis . The predicted protein sequence contains 240 amino acids with a putative signal peptide at the N-terminus and shows approximately 25% identity to other bacterial sodC . Recombinant proteins of a full-length sodC and a truncated form lacking the putative signal peptide were overexpressed in Escherichia coli and affinity purified . Renatured recombinant M . tuberculosis sodC protein possessed characteristics of a Cu,ZnSOD . Immunoblotting with an antiserum against the recombinant M . tuberculosis Cu,ZnSOD allowed detection of a single polypeptide in the lysate of M . tuberculosis . This polypeptide has a similar size as the recombinant protein without the putative signal peptide indicating that the endogenous Cu,ZnSOD in M . tuberculosis might be processed and secreted . Furthermore, immunogold electron microscopic image showed that Cu,ZnSOD is located in the periphery of M . tuberculosis . The enzymatic activity and subcellular localization of this novel Cu,ZnSOD suggest that it may play a role in determining virulence of M . tuberculosis. Microbiol Mol Biol Rev, 1998 Dec, 62(4), 1094 - 156 Molecular biology and pathogenicity of mycoplasmas; Razin S et al.; The recent sequencing of the entire genomes of Mycoplasma genitalium and M . pneumoniae has attracted considerable attention to the molecular biology of mycoplasmas, the smallest self-replicating organisms . It appears that we are now much closer to the goal of defining, in molecular terms, the entire machinery of a self-replicating cell . Comparative genomics based on comparison of the genomic makeup of mycoplasmal genomes with those of other bacteria, has opened new ways of looking at the evolutionary history of the mycoplasmas . There is now solid genetic support for the hypothesis that mycoplasmas have evolved as a branch of gram-positive bacteria by a process of reductive evolution . During this process, the mycoplasmas lost considerable portions of their ancestors' chromosomes but retained the genes essential for life . Thus, the mycoplasmal genomes carry a high percentage of conserved genes, greatly facilitating gene annotation . The significant genome compaction that occurred in mycoplasmas was made possible by adopting a parasitic mode of life . The supply of nutrients from their hosts apparently enabled mycoplasmas to lose, during evolution, the genes for many assimilative processes . During their evolution and adaptation to a parasitic mode of life, the mycoplasmas have developed various genetic systems providing a highly plastic set of variable surface proteins to evade the host immune system . The uniqueness of the mycoplasmal systems is manifested by the presence of highly mutable modules combined with an ability to expand the antigenic repertoire by generating structural alternatives, all compressed into limited genomic sequences . In the absence of a cell wall and a periplasmic space, the majority of surface variable antigens in mycoplasmas are lipoproteins . Apart from providing specific antimycoplasmal defense, the host immune system is also involved in the development of pathogenic lesions and exacerbation of mycoplasma induced diseases . Mycoplasmas are able to stimulate as well as suppress lymphocytes in a nonspecific, polyclonal manner, both in vitro and in vivo . As well as to affecting various subsets of lymphocytes, mycoplasmas and mycoplasma-derived cell components modulate the activities of monocytes/macrophages and NK cells and trigger the production of a wide variety of up-regulating and down-regulating cytokines and chemokines . Mycoplasma-mediated secretion of proinflammatory cytokines, such as tumor necrosis factor alpha, interleukin-1 (IL-1), and IL-6, by macrophages and of up-regulating cytokines by mitogenically stimulated lymphocytes plays a major role in mycoplasma-induced immune system modulation and inflammatory responses. Presse Med, 1998 Oct 31, 27(33), 1694 - 701 {Venous access in oncology}; Lesimple T et al.; INDICATIONS: Many treatments administered to cancer patients require venous access either via a peripheral vein or a larger central vein at the risk of local or systemic infection, thrombus formation or venous occlusion and dysfunction . PRECAUTIONS: Insertion of a central catheter is an invasive procedure which must be conducted under conditions of rigorous asepsia . Strict rules based on well-defined protocols must be applied throughout its use . INFECTIOUS COMPLICATIONS: Local or systemic infectious complications account for 18 to 25% of all nosocomial infections and are often related to colonisation of the puncture site by a Gram positive germ . In case of infection, ablation of the central catheter is not mandatory for diagnosis or antibiotic treatment . THROMBUS FORMATION: Reported at varying frequencies in the literature from 4 to 42%, thrombus formation is unpredictable and often difficult to diagnose . Anticoagulants or fibrolytic agents are indicated but it may also be necessary to withdraw the catheter . MECHANICAL COMPLICATIONS: Displacement, rupture, obstruction and extravasation are frequent complications . Back flow must be checked in all venous accesses and free flow carefully verified . The access must remain patent throughout the period of use, guaranteed by a standard heparinization and rinsing protocol . UNDENIABLE PROGRESS: This complications must not mask the important progress achieved with the use of central venous access for specific and symptomatic treatment in cancer patients. Arch Dis Child Fetal Neonatal Ed, 1998 Sep, 79(2), F105 - 9 Double blind, randomised, placebo controlled study of oral vancomycin in prevention of necrotising enterocolitis in preterm, very low birthweight infants; Siu YK et al.; AIMS: To evaluate the effectiveness of oral vancomycin in the prophylaxis of necrotising enterocolitis in preterm, very low birthweight infants . METHODS: A prospective, double blind, randomised, placebo controlled study in a tertiary referral centre of a university teaching hospital was conducted on 140 very low birthweight infants consecutively admitted to the neonatal unit . The babies were randomly allocated to receive oral vancomycin (15 mg/kg every 8 hours for 7 days) or an equivalent volume of placebo solution . Prophylaxis was started 24 hours before the start of oral feeds . All suspected cases of necrotising enterocolitis were investigated with a full sepsis screen and serial abdominal radiographs . Necrotising enterocolitis was diagnosed and staged according to modified Bell's criteria . RESULTS: Nine of 71 infants receiving oral vancomycin and 19 of 69 infants receiving the placebo solution developed necrotising enterocolitis (p = 0.035) . Infants with necrotising enterocolitis were associated with a significant increase in mortality (p = 0.026) and longer duration of hospital stay (p = 0.002) . CONCLUSIONS: Prophylactic oral vancomycin conferred protection against necrotising enterocolitis in preterm, very low birthweight infants and was associated with a 50% reduction in the incidence . However, widespread implementation of this preventive measure is not recommended, as it would only be effective in necrotising enterocolitis caused by Gram positive organisms and could increase the danger of the emergence of vancomycin resistant or dependent organisms . Its use should be restricted to a high prevalence nursery for a short and well defined period in a selected group of high risk patients. Int J Syst Bacteriol, 1998 Oct, 48 Pt 4, 1223 - 30 Application of the ribonuclease P (RNase P) RNA gene sequence for phylogenetic analysis of the genus Saccharomonospora; Cho M et al.; Sequences of the RNase P RNA gene were investigated for the phylogenetic analysis of the genus Saccharomonospora . Aligned nucleotide sequences, determined from the PCR-amplified RNase P RNA gene of representative strains of the genus Saccharomonospora, displayed 94.2 +/- 1.3% interspecific variances . The intraspecific similarity value was 99.7-100% in all species tested . Saccharomonospora azurea K161T and 'Saccharomonospora caesia' K76T displayed identical RNase P RNA gene sequences in the region that was determined and Saccharomonospora sp . K180 showed sequences distinct from validly described species with a similarity value of 94.6 +/- 1.0% . The phylogenetic trees constructed by aligning the sequences either within the genus Saccharomonospora or with other Gram-positive bacteria were similar to the ones derived using sequences of the 16S rDNA gene . Advantageous features of this gene for application as a molecular phyletic marker are discussed. Int J Syst Bacteriol, 1998 Oct, 48 Pt 4, 1119 - 27 Verrucosispora gifhornensis gen . nov., sp . nov., a new member of the actinobacterial family Micromonosporaceae; Rheims H et al.; A Gram-positive, aerobic, spore-forming actinomycete strain, HR1-2T, was isolated from a peat bog near Gifhorn, Lower Saxony, Germany . Comparative analysis of the 16S rDNA sequence indicated that HR1-2T was phylogenetically related to members of the family Micromonosporaceae, branching adjacent to Spirilliplanes yamanashiensis, Couchioplanes caeruleus, Catenuloplanes japonicus and members of the genus Micromonospora . The affiliation to the family was supported by the presence of family-specific 16S rDNA signature nucleotides, DNA G + C content of 70 mol%, peptidoglycan of type A1 gamma' (directly crossed-linked, presence of glycine, alanine, glutamic acid and mesodiaminopimelic acid in the peptide side-chain), menaquinone MK-9(H4) as the major respiratory lipoquinone, polar lipid composition PII (phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylserine and phosphatidylinositolmannosides) and a glycolyl type of muramic acid . It differed from genera of the family by the lack of arabinose in whole-cell sugars and a unique nucleotide signature stretch between positions 1132 and 1143 (Escherichia coli numbering), 5' CAAUUCGGUUG 3' . Morphologically strain HR1-2T resembles Micromonospora species but can be distinguished from them by the lack of arabinose in whole-cell sugars, the presence of 10-methyl C17:0 fatty acids and a distinct 16S rDNA sequence . Based on the unique combination of morphological, chemotaxonomic and phylogenetic properties a new genus, Verrucosispora gen . nov., is proposed . The type species of this genus is Verrucosispora gifhornensis sp . nov., and the type strain of V . gifhornensis is strain HR1-2T (= DSM 44337T). Infect Immun, 1998 Dec, 66(12), 6030 - 4 Phagocytic and tumor necrosis factor alpha response of human mast cells following exposure to gram-negative and gram-positive bacteria; Arock M et al.; Recent studies have implicated rodent mast cells in the innate immune response to infectious bacteria . We report that cord blood-derived human mast cells (CBHMC) obtained from culture of cord blood progenitors phagocytozed and killed various gram-negative and gram-positive bacteria and simultaneously released considerable amounts of tumor necrosis factor alpha . Overall, the extent of the endocytic and exocytic response of CBHMC correlated with the number of adherent bacteria . Thus, human mast cells are intrinsically capable of mediating microbial recognition and of actively contributing to the host defense against bacteria. Ann Chir Gynaecol, 1998, 87(3), 224 - 8 Clindamycin versus cloxacillin in the treatment of 240 open fractures . A randomized prospective study; Vasenius J et al.; BACKGROUND AND AIMS: Systemic administration of antibiotics is recommended and has proved to lower infection rates in open fractures . However, no antibiotic has proved to be superior to any other . MATERIAL AND METHODS: In a prospective study 227 patients with 240 open fractures were randomized to receive either clindamycin or cloxacillin for infection prevention . RESULTS: The overall infection rate was 15% . Infection occurred in 9.3% of the clindamycin treated and in 20% of the cloxacillin treated fractures (p < 0.05) . In the Gustillo Type I and II open fractures all the pathogens causing infection were gram-positive, while in the Type III open fractures 21 pathogens (57%) were gram-positive and 16 (43%) gram-negative . In the clindamycin treated fractures the infection rates in Type I and II open fractures were 3.3 and 1.8%, respectively, while in the cloxacillin group they were 20 and 3.8%, respectively . Both clindamycin and cloxacillin showed low effectiveness in the treatment of Type III open fractures, the highest infection rates being 75 and 67%, respectively (Type III B) . CONCLUSIONS: Clindamycin provides good antimicrobic coverage against the most common pathogens causing Type I and II open fracture infections . In the treatment of Type III open fractures additional administration of an antibiotic with good gram-negative coverage is recommended. Arch Oral Biol, 1998 Nov, 43(11), 907 - 10 Ultracytochemical localization of hydrogen peroxide production by dental plaque bacteria; Oyarzun A et al.; This study looked for evidence of in vitro hydrogen peroxide (HP) synthesis in human dental plaque, using an ultracytochemical technique that included incubation in a CeCl3-rich medium . Supragingival dental plaque was obtained from periodontally healthy individuals and subgingival dental plaque from human periodontal disease sites . Specificity of the cytochemical reaction was demonstrated using catalase (as HP scavenger) . HP production was indicated by an electron-dense precipitate localized at the cell envelope of unidentified gram-positive and gram-negative bacteria in both supra- and subgingival samples . The ultracytochemical reaction localized the HP production primarily to the plasma membrane and periplasmic space. Arch Surg, 1998 Nov, 133(11), 1241 - 6 Risk factors and clinical impact of central line infections in the surgical intensive care unit; Charalambous C et al.; OBJECTIVE: To determine the risk factors and clinical impact of central line infections in critically ill surgical patients . DESIGN: Retrospective study . SETTING: The surgical intensive care unit of a large tertiary care university hospital . PATIENTS: A total of 232 consecutive central line catheters sent for culture from patients in a surgical intensive care unit during 1996 and 1997 . Catheters were sent for microbiologic analysis when the patient was clinically infected and the central line was a possible source . INTERVENTIONS: None . MAIN OUTCOME MEASURES: Risk factors associated and clinical impact of a positive catheter culture . RESULTS: Of 232 consecutive catheters from 93 patients sent for microbiologic analysis, 114 catheters (49%) had no growth, 40 (17%) were colonized (<15 colonies), and 78 (34%) were considered infected (> or =15 colonies) . Univariate analysis showed that site (internal jugular vs subclavian, P<.001), catheter use (monitoring > dialysis > fluid > nutrition, P=.006), placement in the operating room vs the intensive care unit (P=.02), and placement of a new catheter (> guide wire, > new site, P=.003) were all significant factors . Surprisingly, neither the number of lunmens nor the duration of the catheter in situ were predictors when a catheter was suspected and not proved infected compared with a suspected and proved catheter infection . In the multiple regression model, the placement of the catheter in the internal jugular position was the single most important predictor of a catheter infection (P<.001; odds ratio, 1.83; 95% confidence interval {CI}, 1.41-2.37) . The presence or absence of a specific clinical sign of infection was not predictive of a proved catheter infection . Eighty-six percent of patients had gram-positive bacteria identified on the culture, while the remaining patients had gram-negative bacteria or Candida identified . Of the catheter infections, 68% were monomicrobial, whereas 32% were polymicrobial . Of the catheters sent for microbiologic analysis, 209 (90%) had concurrent peripheral blood cultures for analysis . Nineteen (32%) with no growth from the catheter, and 14 (23%) of colonized catheters had concurrent bacteremia; all had another identifiable cause of infection . Twenty-seven (45%) of infected catheters had a concurrent bacteremia, and 9 of 27 had a second site positive for the same organism . Death related to the infection occurred in 15 patients, 2 in the first 72 hours and 13 in the following 14 days . CONCLUSIONS: Central line infections remain an important cause of morbidity and mortality . Comprehensive review of hospital practices may show a directed focus for performance improvement practices . At our institution, internal jugular catheters have the highest rate of infection . This may suggest breaks in technique during catheter insertion or during catheter maintenance and care. J Infect Dis, 1998 Dec, 178(6), 1649 - 57 Pneumococci stimulate the production of the inducible nitric oxide synthase and nitric oxide by murine macrophages; Orman KL et al.; The role of nitric oxide (NO) in the pathophysiology of gram-positive sepsis is uncertain . In inflammatory conditions, high-output NO production is catalyzed by the enzyme inducible nitric oxide synthase (iNOS) . The ability of 2 strains of pneumococci, pneumococcal cell wall preparations, and purified pneumococcal capsule (Pnu-Imune 23) to trigger the production of iNOS protein and NO in RAW 264.7 murine macrophages was tested . Live pneumococci, oxacillin-killed pneumococci, and pneumococcal cell wall preparations stimulated the production of iNOS and NO by RAW 264.7 cells in the presence, but not the absence, of low concentrations of recombinant murine interferon-gamma . In contrast, purified pneumococcal capsule induced little or no iNOS or NO production by these cells . Thus, pneumococci stimulate high-output NO production by murine macrophages . The potential role of NO in the pathogenesis of pneumococcal sepsis deserves further study. J Zoo Wildl Med, 1998 Sep, 29(3), 315 - 23 Systemic microsporidiosis in inland bearded dragons (Pogona vitticeps); Jacobson ER et al.; One laboratory-hatched and -reared inland bearded dragon (Pogona vitticeps) (No . 1) and two privately owned inland bearded dragons (Nos . 2 and 3) died, showing nonspecific signs of illness . Light microscopic examination of hematoxylin and eosin-stained tissue sections from lizard No . 1 revealed severe hepatic necrosis with clusters of light basophilic intracytoplasmic microorganisms packing and distending hepatocytes and free in areas of necrosis . Similar microorganisms were within cytoplasmic vacuoles in distended renal epithelial cells, pulmonary epithelial cells, gastric mucosal epithelial cells, enterocytes, and capillary endothelial cells and ventricular ependymal cells in the brain . In lizard Nos . 2 and 3, microorganisms of similar appearance were in macrophages in granulomatous inflammation in the colon, adrenal glands, and ovaries . The microorganism was gram positive and acid fast and had a small polar granule that stained using the periodic acid-Schiff reaction . Electron microscopic examination of deparaffinized liver of lizard No . 1 revealed merogonic and sporogonic stages of a protozoan compatible with members of the phylum Microspora . This report provides the first description of microsporidiosis in bearded dragons and is only the second report of this infection in a lizard. East Afr Med J, 1998 Jun, 75(6), 322 - 6 Risk of contamination from air vents during intravenous fluid administration; Useh MF et al.; The microbial effect of creating air-inlet during intravenous fluid administration in different wards of the University of Calabar Teaching Hospital was studied between May and July, 1997 . A total of 123 in-use (test) and 80 unused (control) infusion fluids were studied . Subjects that developed septicaemia following infusion were screened for microbial aetiology . Settle plate cultures were made in all the wards used in the study . Thirty two of in-use infusion fluids (26%) were contaminated, while contamination was not detected among the unused ones . There is a statistically significant relationship in the contamination rate of in-use bags and controls (p < 0.001) . Bags with air-vents were more contaminated 27(49.1%) than those with none, five (7.4%) . The difference in prevalence of contamination rate by air-vent status was statistically significant (p < 0.001) . Gram positive organisms constituted the majority of agents 26(74.3%) . Out of seven subjects that received contaminated fluid, four (57.1%) developed septicaemia . It is concluded that creating air-vent for introduction of additives during intravenous fluid administration provides routes of entry for micro-organisms. J Lipid Res, 1998 Nov, 39(11), 2286 - 92 alpha-d-glucopyranosyl-, d-alanyl- and l-lysylcardiolipin from gram-positive bacteria: analysis by fast atom bombardment mass spectrometry; Peter-Katalinic J et al.; Cardiolipin species substituted on O2 of the middle glycerol moiety with alpha-d-glucopyranosyl, d-alanyl and l-lysyl residues were isolated from different gram-positive bacteria . There respective structures were elucidated by positive and negative mode fast atom bombardment mass spectrometry . The structural heterogeneity due to different fatty acid combinations was documented by up to seven molecular ions . General structural features were derived from diagnostic fragment ions, generated by single cleavage at the phosphodiester moieties in both positive and negative ion mode . A diagnostically important fragment ion for d-alanylcardiolipin was observed in the positive ion mode . It arose from double cleavage of the phosphodiester moieties yielding {NaH(Na) PO4-CH2.CH(OCO.CHNH2.CH3) CH2+}+ . The fatty acid combinations in the phosphatidyl and diacylglycerol ions make it possible to recognize whether saturated and unsaturated fatty acids were selectively or randomly distributed on the two positions of the glycerol moieties . Molecular structures of cardiolipins, derived from mass spectrometric experiments, are in full agreement with those, elucidated by classical chemical analyses. Biochemistry (Mosc), 1998 Sep, 63(9), 1098 - 103 Structure of teichoic acid of the cell wall of Streptomyces sparsogenes VKM Ac-1744T; Shashkov AS et al.; The cell wall of Streptomyces sparsogenes VKM Ac-1744T contains a teichoic acid of 1,3-poly(glycerol phosphate) type . The polymer is composed of about 11 repeating units of the following structure: The structure was not identified in gram-positive bacteria previously . The data are in agreement with DNA-relatedness between Streptomyces sparsogenes and Streptomyces hygroscopicus species and suggest the species-specificity of teichoic acid structure in the studied streptomycetes group. No To Shinkei, 1998 Sep, 50(9), 861 - 70 {A 64-year-old woman with progressive gait disturbance and dementia for one year}; Sugita Y et al.; We report a 64-year-old Japanese woman who died one year after the onset of progressive gait disturbance and dementia . She noted a difficulty in holding a glass and hand tremor in June of 1996 when she was 63 years old . In July of 1996, she tended to lean toward left when she walked . She also noted truncal titubation . In November of 1996, she started to have visual hallucination and delusion in which she said "I see something is flying on the wall.", "Somebody has come into my room", and things like that . She was admitted to our service on November 22, 1996 . On admission, she was alert and general physical examination was unremarkable . Neurologic examination revealed disturbance in recent memory . Hasegawa's dementia rating scale was 22/30 . She showed vivid visual hallucination with colors in which she saw faces of dwarfs and angels, a space ship, and others . Higher cerebral functions were normal . She showed left oculomotor palsy which was a sequel of an aneurysm and subarachnoid hemorrhage nine years before . Otherwise cranial nerves were unremarkable . She showed ataxic gait, limb ataxia, truncal titubation, and postural hand tremor . She had no weakness and no muscle atrophy . Deep tendon reflexes were within normal limits . Plantar response was flexor . Sensation was intact . Laboratory examination was also unremarkable . Complete survey for occult malignancy was negative . CSF was under a normal pressure and cell count was 1/microliter, total protein 27 mg/dl, and sugar 68 mg/dl . Cranial CT scan was unremarkable . MRI was not obtained because of the presence of an aneurysm clip in the left internal carotid-posterior communication artery junction . She showed progressive deterioration in her mental function . By January 1997, she became unable to stand or walk with marked dementia . Repeated CSF exams and cranial CT scans were unremarkable . She suffered from several episodes of aspiration pneumonia . A trial of three days methylprednisolone pulse therapy was given starting on March 7, 1997, which was of no effect on her neurologic status . On March 28, 1997, she was intubated because of acute respiratory distress syndrome . In April 2, her body temperature rose to 38 degrees C . On April 9, 1997, her blood pressure dropped and resuscitation was unsuccessful . She was pronounced dead on the same day . The patient was discussed in a neurologic CPC and the chief discussant arrived at the conclusion that the patient had primary leptomeningeal lymphoma . Other possibilities entertained among the audience included brain stem encephalitis of unknown type, carcinomatous cerebellar degeneration plus limbic encephalitis, Creutzfeldt-Jakob disease, thalamic degeneration, and progressive multifocal leukoencephalopathy . Post-mortem examination revealed thickening and clouding of the leptomeninges; Gram-positive diplococci were found in the leptomeninges . This meningitis appeared to have been an complication in the terminal stage of her illness . Microscopic examination revealed astrocytosis in the midbrain tegmentum . Cerebral cortices showed only mild astrtocytosis . No cerebellar atrophy was seen and Purkinje cells were retained which excluded paraneoplastic cerebellar degeneration . Neuropathologic diagnosis was bacterial meningitis, however, the presence of brain stem encephalitis prior to the onset of bacterial meningitis could not be excluded . It is interesting to note that the diagnosis of the primary neurologic disease of this patient was not easy even after autopsy . As autopsy permission was obtained only for the brain, it was not clear whether or not this patient had an occult malignancy somewhere in her body, however, there was no evidence to indicate paraneoplastic degeneration of the central nervous system . As the patient did not have meningeal signs until one month before her death, it is difficult to ascribe her entire neurologic problems to her meningitis . Finally, her visual hallucination was vivid and colorful; we thought this might have been J Clin Invest, 1998 Oct 15, 102(8), 1540 - 50 Exposure to bacterial products renders macrophages highly susceptible to T-tropic HIV-1; Moriuchi M et al.; Microbial coinfections variably influence HIV-1 infection through immune activation or direct interaction of microorganisms with HIV-1 or its target cells . In this study, we investigated whether exposure of macrophages to bacterial products impacts the susceptibility of these cells to HIV-1 of different cellular tropisms . We demonstrate that () macrophages exposed to bacterial cell wall components such as lipopolysaccharide (LPS) (Gram-negative rods), lipoteichoic acid (Gram-positive cocci), and lipoarabinomannan (Mycobacteria) become highly susceptible to T cell (T)-tropic HIV-1 (which otherwise poorly replicate in macrophages) and variably susceptible to macrophage (M)-tropic HIV-1; () LPS-stimulated macrophages secrete a number of soluble factors (i.e., chemokines, interferon, and proinflammatory cytokines) that variably affect HIV infection of macrophages, depending on the virus phenotype in question; and () LPS-stimulated macrophages express CCR5 (a major coreceptor for M-tropic HIV-1) at lower levels and CXCR4 (a major coreceptor for T-tropic HIV-1) at higher levels compared with unstimulated macrophages . We hypothesize that a more favorable environment for T-tropic HIV-1 and a less favorable or even unfavorable environment for M-tropic HIV-1 secondary to exposure of macrophages to those bacterial products may accerelate a transition from M- to T-tropic viral phenotype, which is indicative of disease progression. Ophthalmology, 1998 Oct, 105(10), 1891 - 6 Whipple's syndrome (uveitis, B27-negative spondylarthropathy, meningitis, and lymphadenopathy) associated with Arthrobacter sp . infection; Bodaghi B et al.; OBJECTIVE: To report an unusual case of Whipple's disease, including uveitis, seronegative spondylarthropathy, meningitis, and lymphadenopathy, associated with an Arthrobacter sp . infection . DESIGN: Interventional case report . PATIENT AND INTERVENTION: A 60-year-old white man presenting with severe chronic uveitis and systemic inflammatory manifestations was treated efficiently for Whipple's disease after histopathologic analysis of vitreous and inguinal adenopathy biopsy specimens . The authors performed a retrospective, laboratory-based evaluation of stored tissue specimens . MEASUREMENTS: Molecular analysis based on 16S ribosomal RNA gene amplification was applied to pretreatment biopsy specimens of inguinal lymph node to identify a causative bacterial agent . RESULTS: Tropheryma whippelii genome was not detected in these specimens . However, an amplification product was obtained after the first polymerase chain reaction run and subsequently was sequenced . It corresponded to an Arthrobacter sp., a gram-positive agent presenting diagnostic patterns and therapeutic management similar to those of Whipple's disease caused by T . whippelii . CONCLUSION: The absence of T . whippelii identification by molecular amplification during a clinically and histologically oriented Whipple's syndrome should not rule out the diagnosis . Arthrobacter infection may represent a new bacterial etiology of systemic inflammatory disorders involving the eye and associated with periodic acid-Schiff-positive inclusions. Proc Int Conf Intell Syst Mol Biol, 1998, 6, 122 - 30 Prediction of signal peptides and signal anchors by a hidden Markov model; Nielsen H et al.; A hidden Markov model of signal peptides has been developed . It contains submodels for the N-terminal part, the hydrophobic region, and the region around the cleavage site . For known signal peptides, the model can be used to assign objective boundaries between these three regions . Applied to our data, the length distributions for the three regions are significantly different from expectations . For instance, the assigned hydrophobic region is between 8 and 12 residues long in almost all eukaryotic signal peptides . This analysis also makes obvious the difference between eukaryotes, Gram-positive bacteria, and Gram-negative bacteria . The model can be used to predict the location of the cleavage site, which it finds correctly in nearly 70% of signal peptides in a cross-validated test--almost the same accuracy as the best previous method . One of the problems for existing prediction methods is the poor discrimination between signal peptides and uncleaved signal anchors, but this is substantially improved by the hidden Markov model when expanding it with a very simple signal anchor model. Pediatr Cardiol, 1998 Nov-Dec, 19(6), 482 - 6 Severe left ventricular dysfunction and arrhythmias as complications of gram-positive sepsis: rapid recovery in children; Ferdman B et al.; Severe left ventricular dilatation and dysfunction in children may be associated with poor outcome in as many as 45% of cases . The prognosis for children with poor left ventricular function or arrhythmias associated with septic shock may be better, however, this has been inadequately studied . We report the favorable outcome of three children who presented with Gram-positive sepsis and significant cardiovascular compromise-two with severely dilated, poorly contractile left ventricle, and one with mild left ventricular dysfunction and incessant, malignant, and rapid atrial and ventricular arrhythmias . Our experience with these patients shows that complete and rapid resolution of these complications may be achieved with aggressive therapy. Pathol Biol (Paris), 1998 Jun, 46(6), 442 - 8 {Peptostreptococcus magnus osteoarticular infections after orthopedic surgery . 14 cases and pathogenicity factors}; Felten A et al.; We report a retrospective study of 14 Peptostreptococcus magnus bone and joint infections, following orthopaedic prostheses or implantation of fixation devices, diagnosed in two Paris hospitals between 1992 and 1996 . Five patients experienced a knee joint infection after anterior cruciate ligament reconstruction with 4 artificial grafts, and 9 caught joint or wound infections, after limb traumatic injuries or bone neoplastic ruptures involving femur, tibia, calcaneum and humerus, treated by arthroplasty or osteosynthesis with implantation of biomaterials . Septic arthritis was experienced one week to one year after reconstructive surgery, and had evolved for several months to years before etiologic diagnosis in 5 cases . Specimens of pus, tissues or removed implants produced numerous slow growing small colonies of Gram positive cocci arranged in clumps on culture media incubated in anaerobic atmosphere only . In 10 patients, the same organism was disclosed in several separate specimens . The identification of P . magnus was assessed by the enzyme profile (rapid ID 32A API strips), gaz liquid chromatography, catalase and coagulase production, resistance to novobiocin and Na polyanethol sulphonate . Antibiotic sensitivity testing performed by disc method was constant to penicillin G, amoxicillin, cefuroxime, cefoxitin, imipenem and pristinamycin with penicillin G MICs < 0.125 mg/l and metronidazole MICs < 1 mg/l . Erythromycin, clindamycin, rifampicin, tetracycline and fosfomycin were active against more than 70% of P . magnus . All patients were cured after a prolonged course of various antibiotics and surgical removal of the foreign material whenever possible . We studied in vitro binding of P . magnus with extracellular matrix proteins adsorbed onto biomaterials, by particle agglutination assays of latex beads coated with proteins . Eighty one% of strains bound to collagen, 69% to fibrinogen and 46% to fibronectin . Comparison of orthopaedic strains with strains of other infections and from skin showed a correlation between P . magnus from bone and joint infections and their fibrinogen binding ability (69% against 20%, p < 0.05). Neurosurgery, 1998 Oct, 43(4), 937 - 40 Cervical actinomycosis causing spinal cord compression and multisegmental root failure: case report and review of the literature; Oruckaptan HH et al.; OBJECTIVE AND IMPORTANCE: Epidural invasion and the resulting cord compression are clinical entities not usually associated with actinomycosis, and we found only 11 reported cases of cord compression caused by Actinomyces infection in the literature . Only one reported case was described as actinomycosis with epidural granuloma (14, 16), whereas in the other cases, epidural macroabscess (phlegm) formation caused the symptoms . Histopathological demonstration of the inflammatory granulation tissue and gram-positive sulfur-containing filamentous bacteria are important for the diagnosis of actinomycosis, because the clinical and microbiological studies cannot always demonstrate the causative microorganism and primary infection source . CLINICAL PRESENTATION: In this article, a case of Actinomyces infection causing cervical cord compression is presented . Precise diagnosis was accomplished using specific histopathological studies of the surgical specimens; such a precise diagnosis cannot always be achieved using preoperative investigations and microbiological studies . The treatment modalities and the patient's outcome are also discussed . CONCLUSION: As shown by hematoxylin and eosin stain, in contrast to the Nocardia species, Actinomyces filaments histopathologically are basophilic in nature and terminate in eosinophilic clubs as a predictive feature . The clinical and radiological findings closely resemble metastatic tumors and other infectious processes . A differential diagnosis is also emphasized in this article, along with a review of the literature. Eur J Clin Microbiol Infect Dis, 1998 Jul, 17(7), 464 - 9 Bacterial DNA as an evolutionary conserved ligand signalling danger of infection to immune cells; Heeg K et al.; During infection, the innate limb of the immune system senses danger (pathogens) via constitutively expressed pattern-recognition receptors, and responds with activation and secretion of pro-inflammatory cytokines . Cell-wall components of gram-positive and gram-negative bacteria, such as peptidoglycan, endotoxin or lipoteichoic acid, activate via CD14, a prototypic pattern-recognition receptor for carbohydrates . This review article focuses on an alternative recognition system of the innate immune system for the recognition of bacterial DNA . Bacterial DNA differs from eukaryotic DNA in its frequency of the dinucleotides CG and its lack of methylation . These structural differences appear to be sensed by cells of the innate immune system such as antigen-presenting cells . As a consequence bacterial DNA serves as an alternate ligand to signal danger of infection . Bacterial DNA and (synthetic) oligonucleotides (ODN) derived thereof are as efficient as endotoxin in activating macrophages and dendritic cells and in triggering release of pro-inflammatory cytokines . In mice sensitized with D-galactosamine (D-GalN), high doses of bacterial DNA from either gram-positive or gram-negative pathogens induce a lethal cytokine syndrome (lethal shock) . Therefore, bacterial DNA may represent a hitherto unrecognized pathophysiological entity in host-parasite interactions . Moreover, recent evidence suggests that bacterial DNA or immunostimulating ODN triggers the immunostimulation of antigen-presenting cells, and can be utilized as adjuvant to enhance immune responses of the adaptive immune system towards poorly immunogenic antigens . In fact, foreign DNA might be useful as immunotherapeutically active adjuvant to direct adaptive immune responses towards Thl-dominated immune reactions . If these findings are operative in humans, immunostimulating ODN might be used to influence Th2-dominated diseases such as allergy. Eur J Biochem, 1998 Sep 1, 256(2), 325 - 33 Hypothermia enhances the biological activity of lipopolysaccharide by altering its fluidity state; Luhm J et al.; Lipopolysaccharides (LPS, endotoxin) of gram-negative bacteria are among the main causes of sepsis and septic shock . In the present study, the influence of temperature on the biological activity of LPS was investigated . Lowering the temperature from 37 degrees C to 34.5 degrees C or to 30 degrees C significantly enhances in vitro tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-6 release induced by different LPS chemotypes and heat-inactivated Escherichia coli . This cytokine-increasing effect of lowering the temperature is highly mediated by serum proteins, particularly by LPS-binding protein (LBP) and low-density lipoproteins (LDL) . In contrast, cytokine production induced by the superantigen toxic shock syndrome toxin-1 (TSST-1) from Gram-positive Staphyloccoccus aureus decreases by around 70% at 30 degrees C as compared with 37 degrees C, corresponding to the expected effect of change in temperature and regardless of the presence of serum proteins . In order to explain the unexpected biological hypothermia effect with regard to LPS, the fluidity state of the lipid A portion of LPS as one important physico-chemical property possibly involved was investigated . The fluidity, determined by fluorescence polarization measurements, was found to decrease with decreasing temperature . These data suggest that a low fluid LPS chemotype is biologically more active than a more fluid one (and vice versa) . Statistical analysis of the results shows a strong correlation between cytokine secretion and fluidity state of a given LPS chemotype (0.71 < r < 0.89, all P<0.01) . As a clinical consequence, these data may be one possible explanation for the higher mortality rate of hypothermic Gram-negative sepsis. Hepatogastroenterology, 1998 Jul-Aug, 45(22), 1018 - 22 Diagnosis of small intestinal bacterial overgrowth in clinical praxis: a comparison of the culture of small bowel aspirate, duodenal biopsies and gastric aspirate; Stotzer PO et al.; BACKGROUND/AIMS: This study was undertaken to validate the usefulness of the culture of duodenal biopsy specimens and gastric aspirate compared to the culture of small bowel aspirate for diagnosing small intestinal bacterial overgrowth . We also investigated the occurrence of predisposing conditions in these patients . METHODOLOGY: Seventy five consecutive patients, admitted because of symptoms which caused us to suspect small intestinal bacterial overgrowth, were studied . For all patients, specimens for the culture of small bowel aspirate, duodenal biopsies and gastric aspirate were obtained during upper endoscopy . RESULTS: Eighteen patients showed growth of gram negative bacteria, 22 growth of gram positive bacteria and 35 showed no significant growth in cultures of small bowel aspirate . Cultures of duodenal biopsies revealed gram negative bacteria in 11 patients, gram positive bacteria in 9 and no growth in 55 . Cultures of gastric aspirate revealed gram negative bacteria in 7 patients, gram positive bacteria in 12 and no growth in 51 . Ten of the 18 patients with gram negative overgrowth and 13 of the 22 patients with gram positive overgrowth had a predisposing condition . In contrast, only 4 of the 35 without overgrowth had a predisposing condition . CONCLUSIONS: The culture of duodenal biopsy specimens or gastric aspirate is a less sensitive method than the culture of small bowel aspirate . Most patients with culture-proven small intestinal bacterial overgrowth had at least one predisposing condition. EMBO J, 1998 Oct 1, 17(19), 5776 - 82 sigmaR, an RNA polymerase sigma factor that modulates expression of the thioredoxin system in response to oxidative stress in Streptomyces coelicolor A3(2); Paget MS et al.; We have identified an RNA polymerase sigma factor, sigmaR, that is part of a system that senses and responds to thiol oxidation in the Gram-positive, antibiotic-producing bacterium Streptomyces coelicolor A3(2) . Deletion of the gene (sigR) encoding sigmaR caused sensitivity to the thiol-specific oxidant diamide and to the redox cycling compounds menadione and plumbagin . This correlated with reduced levels of disulfide reductase activity and an inability to induce this activity on exposure to diamide . The trxBA operon, encoding thioredoxin reductase and thioredoxin, was found to be under the direct control of sigmaR . trxBA is transcribed from two promoters, trxBp1 and trxBp2, separated by 5-6 bp . trxBp1 is transiently induced at least 50-fold in response to diamide treatment in a sigR-dependent manner . Purified sigmaR directed transcription from trxBp1 in vitro, indicating that trxBp1 is a target for sigmaR . Transcription of sigR itself initiates at two promoters, sigRp1 and sigRp2, which are separated by 173 bp . The sigRp2 transcript was undetectable in a sigR-null mutant, and purified sigmaR could direct transcription from sigRp2 in vitro, indicating that sigR is positively autoregulated . Transcription from sigRp2 was also transiently induced (70-fold) following treatment with diamide . We propose a model in which sigmaR induces expression of the thioredoxin system in response to cytoplasmic disulfide bond formation . Upon reestablishment of normal thiol levels, sigmaR activity is switched off, resulting in down-regulation of trxBA and sigR . We present evidence that the sigmaR system also functions in the actinomycete pathogen Mycobacterium tuberculosis. Bull Cancer, 1998 Aug, 85(8), 695 - 711 {Standards, Options, and Recommendations for the management of brief neutropenias . Fedération Nationale des Centres de Lutte Contre le Cancer}; Biron P et al.; CONTEXT: The "Standards, Options and Recommendations" (SOR), initiated in 1993, is a collaborative project between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics . The main objective is the development of clinical practice guidelines to improve the quality of health care and outcomes for cancer patients . The methodology is based on literature review and critical appraisal by a multidisciplinary experts group, with feedback from specialists in cancer care delivery . OBJECTIVE: To develop a clinical practice guideline for the management of neutropenic cancer patients (excluding prolonged neutropenia) . METHODS: Data have been identified by literature search using Medline and Current Contents (up to February 1997) and personal reference lists . The main end points considered were mortality, morbidity, risk factors, fever, source of infection, microbiological documentation, incidence and length of hospital stays, quality of life, efficacy of treatment, safety and costs . Once the guideline was defined, the document was submitted to 48 reviewers for peer review and to the medical committees of the 20 French Cancer Centres for review and agreement . RESULTS: The key recommendations are: 1) before receiving cytotoxic chemotherapy, patients must be informed of potential risks and precautions to observe; 2) non-febrile neutropenic patients can be followed at home (except specific context); antibiotic prophylaxis is not recommended; 3) initial empirical antibiotic therapy for febrile patients is mandatory, whether associated beta-lactam and aminoglycoside, or monotherapy with a broad-spectrum beta-lactam (except in case of septic shock or pneumopathy) . A glycopeptide can be added in case of overt catheter-related or cutaneous infection, in case of microbiologically documented infection with a oxacillin-resistant Gram positive bacteria, or in case of persistent fever in a clinically deteriorating patient; 4) at the present time, there is insufficient evidence to recommend the management of febrile neutropenic patients at home . We recommend participation in studies to identify predicting factors of low-risk patients and to assess the feasibility and safety of early discharge and home therapy. Br J Haematol, 1998 Sep, 102(5), 1284 - 91 Prolonged but reversible neutrophil dysfunctions differentially sensitive to granulocyte colony-stimulating factor in children with acute lymphoblastic leukaemia; Lejeune M et al.; Treatment of average-risk acute lymphoblastic leukaemia (ALL) in children consists of 6 months of intensive chemotherapy followed by 18 months of maintenance therapy . Polymorphonuclear leucocyte (PMN) functions from children with ALL were studied in order to evaluate and compare the toxicity of the initial intensive treatment with the toxicity of the subsequent less intensive maintenance treatment . H2O2 and O2- production, evaluated by chemiluminescence, were significantly decreased during the intensive period but returned to normal values when maintenance therapy began . In contrast, bactericidal activity against Gram-positive and Gram-negative microorganisms remained at low levels throughout the treatment but returned to normal values in patients off chemotherapy . PMN from patients on maintenance therapy exhibited an excess of morphological changes associated with apoptosis . This was confirmed by standard two-colour flow cytometry which revealed an increase in the number of hypodiploid cells, and increased expression of membrane phosphatidylserine together with a drastic reduction in the expression of the Fcgamma receptor IIIB (CD16) . These defective PMN were differentially sensitive to the effects of granulocyte colony stimulating factor (G-CSF): G-CSF induced similar increase in chemiluminescence in control and patient PMN; GSF partially corrected the defective bactericidal activity; G-CSF did not affect the accelerated PMN apoptosis . These observations indicate that ALL children undergoing chemotherapy present PMN defective functions which are partially sensitive or even resistant to G-CSF. Symp Ser Soc Appl Microbiol, 1998, 27, 127S - 137S Bacterial phospholipases; Titball RW; The phospholipases are a diverse group of enzymes, produced by a variety of Gram-positive and Gram-negative bacteria . The roles of these enzymes in the pathogenesis of infectious disease is equally diverse . It is only recently that molecular genetic approaches have allowed data to be obtained which indicates the role of these enzymes in the disease process . In the case of some pathogens phospholipases play an overriding role in disease . Roles for these enzymes have been demonstrated in the pathogenesis of disease caused by extracellular and intracellular pathogens and by disease caused by pathogens which enter via the respiratory tract, the intestinal tract or after traumatic injury . Some of the mechanisms by which phospholipases C affect tissues in vitro or ex vivo are understood but, in the main, the mechanisms by which phospholipases C affect tissues in vivo are not known . A key event, which can determine the extent of involvement of phospholipases in the disease process, is the interaction of the enzyme with phospholipids in eukaryotic cell membranes . Whilst progress has been made in understanding the molecular basis of these interactions, the process is far from understood . Two theories attempt to explain the reasons why only some phospholipases C are membrane active . In general, the membrane active enzymes are able to hydrolyse both phosphatidylcholine and sphingomyelin and appear to have mechanisms which allow them to interact with membrane phospholipids . The structural differences between phosphatidylcholine and sphingomyelin lie within the fatty acyl chain/ester bond region which would be partially embedded in the membrane bilayer . Therefore, there may be a common explanation for membrane interaction and recognition of both phospholipid types . The value of this information will be several fold . The demonstration of the role of these enzymes in disease will allow the development of vaccines or therapeutics which block the effects of these enzymes . In this context it is worth bearing in mind that eukaryotic phospholipases C, which play key roles in many inflammatory and autoimmune diseases, are the subject of intense study by the pharmaceutical industry . Some of the bacterial toxins are potent cytotoxic agents and this has encouraged some workers to explore the possibility that immunotoxins can be developed (Chovnick et al . 1991) . Purified recombinant phospholipases C will continue to be used in the study of cell membranes, and the increasing numbers of enzymes with different substrate specificities will enhance their application. J Appl Microbiol, 1998 Aug, 85(2), 309 - 16 Isolation of isoproturon-degrading bacteria from treated soil via three different routes; Roberts SJ et al.; Three different isolation routes (flask enrichment/flask degradation assay, flask enrichment/microplate degradation assay, MPN assay/microplate degradation assay) were used to obtain pure cultures of bacteria which degraded isoproturon (3-(4-isopropylphenyl)-1,1-dimethylurea) as sole carbon and nitrogen source in a mineral salts medium from a field soil treated with isoproturon in the laboratory . All three isolation routes were successful, but the microplate assay of degradation was more successful than the flask assay . Characterization of 36 isolates indicated that they formed 16 distinct phenotypes (10 Gram-positive phenotypes, six Gram-negative phenotypes) which are likely to represent distinct species . Low concentrations of the degradation product 3-(4- isopropylphenyl)-1-methylurea (IPPMU) were occasionally found in the culture solutions . When provided as the sole source of carbon and nitrogen, the monomethyl degradation product was itself rapidly degraded by several of the isolates . Some isolates were also able to use the demethylated degradation product 3-(4-isopropylphenyl)-urea (IPPU) as sole source of carbon and nitrogen, although there was occasionally an extended lag-phase before rapid degradation commenced . One isolate was particularly active and degraded isoproturon, the monomethyl and demethylated degradation products of isoproturon, and demethylated the related phenylureas diuron and linuron. J Appl Microbiol, 1998 Sep, 85(3), 574 - 82 Changes in bacterial populations in the colon of pigs fed different sources of dietary fibre, and the development of swine dysentery after experimental infection; Durmic Z et al.; Swine dysentery (SD) is a disease which can be controlled by feeding a diet low in dietary fibre . The influence of source and inclusion level of dietary fibre both on bacterial populations in the colon, and on subsequent development of SD in pigs experimentally infected with Serpulina hyodysenteriae was evaluated . In Experiment 1, pigs were fed a low-fibre diet based on cooked rice and a animal protein supplement, or the same diet containing added insoluble (iNSP, fed as oaten chaff) or soluble (sNSP, fed as guar gum) non-starch polysaccharides, resistant starch (RS), or a combination of the last two (sNSP/RS) . In Experiment 2, different levels of RS were added to the diet . With the base rice diet and with the addition of iNSP, the total number of colonic bacteria was low, the Gram-positive population predominated, S . hyodysenteriae did not colonize and SD did not develop . Synergistic bacteria (Fusobacterium necrophorum and Fus . nucleatum), which have been reported to facilitate colonization by S . hyodysenteriae, were found only among isolates from pigs fed the sNSP/RS diet, and these animals developed SD . Addition of RS to the diet increased total bacterial counts and stimulated growth of Gram-negative bacteria in the colon . In Experiment 1, this permitted colonization by S . hyodysenteriae, but not expression of SD . In contrast, in Experiment 2, this level of inclusion and two others allowed both colonization and development of SD . In conclusion, the addition of sNSP and/or RS to an otherwise protective rice-based diet generated changes in the large intestine microbiota which might have some influence on proliferation of S . hyodysenteriae and the development of SD. Eur J Epidemiol, 1998 Jul, 14(5), 519 - 20 Failure to recognize rapidly growing mycobacteria in a proficiency testing sample without specific request--a wider diagnostic problem? von Graevenitz A, Punter-Streit V. Fifty participants in the Swiss External Quality Control Program in Bacteriology/Mycology received a diagnostic sample containing Mycobacterium fortuitum . Only 31 used some sort of acid-fast stains, and 13 reported the diagnosis of M . fortuitum or rapidly growing mycobacteria . We conclude that the presence of 'rapid growers' in routine bacteriology samples is underestimated, and that acid-fast stains should be performed on suspicious Gram-positive rods. FEBS Lett, 1998 Sep 4, 434(3), 325 - 8 Structure of the Na+-driven flagellum from the homoacetogenic bacterium Acetobacterium woodii; Aufurth S et al.; The Na+-dependent flagellum of Acetobacterium woodii was characterised . Flagellin and whole flagella were purified and analysed by SDS-PAGE and electron microscopy . The structure and dimensions of the filament and the hook-basal body, as revealed by electron microscopy, resemble those of H+-dependent flagella from gram-positive bacteria . Intramembrane particle rings were present at the cell pole in freeze-fractured A . woodii cells, which might correspond to the mot complex. J Clin Microbiol, 1998 Oct, 36(10), 3090 - 3 Description of Gemella sanguinis sp . nov., isolated from human clinical specimens; Collins MD et al.; Six strains of a hitherto undescribed gram-positive, catalase-negative, facultatively anaerobic coccus isolated from human sources were characterized by phenotypic and molecular taxonomic methods . Comparative 16S rRNA gene sequencing studies demonstrated that the unknown strains were genealogically identical and constitute a new subline within the genus Gemella . The unknown bacterium was readily distinguished from Gemella haemolysans, Gemella bergeriae, and Gemella morbillorum by biochemical tests and electrophoretic analysis of whole-cell proteins . Based on phylogenetic and phenotypic evidence, it is proposed that the unknown bacterium be classified as Gemella sanguinis sp . nov . The type strain is CCUG 37820(T). Int J Syst Bacteriol, 1998 Jul, 48 Pt 3, 769 - 74 Pseudoalteromonas bacteriolytica sp . nov., a marine bacterium that is the causative agent of red spot disease of Laminaria japonica; Sawabe T et al.; An aerobic, polarly flagellated marine bacterium that produces a prodigiosin-like pigment was isolated from the red-spotted culture beds of Laminaria japonica . Five isolates had unique bacteriolytic activity for both Gram-positive and -negative bacteria, which had never been observed among Alteromonas or related species . The isolates were identified as the causative agent of red spot disease of L . japonica seeds . The phenotypic features of the isolates were similar to these of Pseudoalteromonas rubra ATCC 29570T, but they could be differentiated using 10 traits (growth at 37 degrees C, requirement for organic growth factors, bacteriolytic activity, utilization of sucrose, N-acetylglucosamine, fumarate, succinate, D-galactose, L-proline and acetate) . The G+C content of DNAs from the isolates was 44-46 mol% . The isolates constitute a new species, distinct from the other Alteromonas and Pseudoalteromonas species, as shown by DNA-DNA hybridization experiments and phylogenetic clustering of 16S rRNA gene sequences, for which the name Pseudoalteromonas bacteriolytica sp . nov . (type strain = IAM 14595T) is proposed . A set of phenotypic features which differentiate this new species from closely related Pseudoalteromonas and Alteromonas species is provided. J Biol Chem, 1998 Sep 18, 273(38), 24912 - 20 Mutations in and monoclonal antibody binding to evolutionary hypervariable region of Escherichia coli RNA polymerase beta' subunit inhibit transcript cleavage and transcript elongation; Zakharova N et al.; A 190 amino acid-long region centered around position 1050 of the 1407-amino acid-long beta' subunit of Escherichia coli RNA polymerase (RNAP) is absent from homologues in eukaryotes, archaea and many bacteria . In chloroplasts, the corresponding region can be more than 900 amino acids long . The role of this hypervariable region was studied by deletion mutagenesis of the cloned E . coli rpoC, encoding beta' . Long deletions mimicking beta' from Gram-positive bacteria failed to assemble into RNAP . Mutants with short, 40-60-amino acid-long deletions spanning beta' residues 941-1130 assembled into active RNAP in vitro . These mutant enzymes were defective in the transcript cleavage reaction and had dramatically reduced transcription elongation rates at subsaturating substrate concentrations due to prolonged pausing at sites of transcriptional arrest . Binding of a monoclonal antibody, Pyn1, to the hypervariable region inhibited transcription elongation and intrinsic transcript cleavage and, to a lesser degree, GreB-induced transcript cleavage, but did not interfere with GreB binding to RNAP . We propose that mutations in and antibody binding to the hypervariable, functionally dispensable region of beta' inhibit transcript cleavage and elongation by distorting the flanking conserved segment G in the active center. Bone Marrow Transplant, 1998 Sep, 22(5), 503 - 5 Oerskovia xanthineolytica: a new pathogen in bone marrow transplantation; Ellerbroek P et al.; A 53-year-old woman with non-Hodgkin lymphoma underwent an autologous bone marrow transplant (BMT) . Incomplete reconstitution necessitated the use of a long-term central venous catheter . One year after BMT she presented with fever . Echocardiography revealed vegetations on the tricuspid valve . Gram-positive rods grown from blood cultures and catheter tip were identified as Oerskovia xanthineolytica . We report the first case of native valve endocarditis caused by this organism. Int Orthop, 1998, 22(3), 178 - 81 The Girdlestone pseudarthrosis in the treatment of infected hip replacements; Castellanos J et al.; The results of 78 resections of the head and neck of the femur (Girdlestone pseudarthrosis) in patients with infected hip replacements were studied . The mean follow-up was 5 years . At the time of the resection, gram-positive organisms were found in 53% of the cases, gram-negative in 33%, and in 12% there were mixed flora . The Girdlestone pseudarthrosis controlled the infection in 86% and achieved satisfactory relief of pain in 83% . The mean shortening of the limb was 4.1 cm and every patient needed some type of external walking aid . We found no correlation between the type of organisms and the persistence of infection, nor between shortening and the functional results . The Girdlestone pseudarthrosis is an acceptable method of controlling infection and relieving pain after infection of a total hip replacement. Am Ind Hyg Assoc J, 1998 Aug, 59(8), 524 - 31 Total and viable airborne bacterial load in two different agricultural environments using gas chromatography-tandem mass spectrometry and culture: a prototype study; Krahmer M et al.; Airborne exposure to bacterial components found in agricultural environments can lead to pulmonary inflammation . Total (viable and nonviable) bacterial load was monitored in a stable and a dairy by a new approach, gas chromatography-tandem mass spectrometry measurement of muramic acid, a component of gram positive and gram negative bacterial peptidoglycan . Also used to assess the gram negative bacterial load were 3-hydroxy fatty acids, markers of bacterial lipopolysaccharide . Culture, an established procedure for assessing the viable bacterial portion of airborne dust, served as a basis for comparison . The muramic acid and 3-hydroxy fatty acid concentrations (total C12:0, C14:0, and C16:0) showed a correlation with an R2 of 0.81 . Dust and muramic acid levels also correlated . However, although relative muramic acid levels were lower in the stable than the dairy, colony forming units (CFU) were considerably higher in the stable . The total bacterial load (estimated from muramic acid values) for both the stable and dairy was also higher than would have been predicted from culture . These results suggest that nonculture based approaches and culture provide complementary but independent measurements of airborne biopollution. Nucleic Acids Res, 1998 Sep 15, 26(18), 4093 - 9 Evolutionary variation in bacterial RNase P RNAs; Haas ES et al.; Sequences encoding RNase P RNAs from representatives of the last remaining classical phyla of Bacteria have been determined, completing a general phylogenetic survey of RNase P RNA sequence and structure . This broad sampling of RNase P RNAs allows some refinement of the secondary structure, and reveals patterns in the evolutionary variation of sequences and secondary structures . Although the sequences range from 100 to <25% identical to one another, and although only 40 of the nucleotides are invariant, there is considerable conservation of the underlying core of the RNA sequence . RNase P RNAs, like group I intron RNAs but unlike ribosomal RNAs, transfer RNAs or other highly conserved RNAs, are quite variable in secondary structure outside of this conserved structural core . Conservative regions of the RNA evolve by substitution of apparently interchangeable alternative structures, rather than the insertion and deletion of helical elements that occurs in the more variable regions of the RNA . In a remarkable case of convergent molecular evolution, most of the unusual structural elements of type B RNase P RNAs of the low G+C Gram-positive Bacteria have evolved independently in Thermomicrobium roseum , a member of the green non-sulfur Bacteria. Mol Microbiol, 1998 Jul, 29(2), 397 - 407 Regulation of compatible solute accumulation in bacteria; Poolman B et al.; In their natural habitats, microorganisms are often exposed to osmolality changes in the environment . The osmotic stress must be sensed and converted into an activity change of specific enzymes and transport proteins and/or it must trigger their synthesis such that the osmotic imbalance can be rapidly restored . On the basis of the available literature, we conclude that representative gram-negative and gram-positive bacteria use different strategies to respond to osmotic stress . The main focus of this paper is on the initial response of bacteria to hyper- and hypo-osmotic conditions, and in particular the osmosensing devices that allow the cell to rapidly activate and/or to synthesize the transport systems necessary for uptake and excretion of compatible solutes . The experimental data allow us to discriminate the transport systems by the physicochemical parameter that is sensed, which can be a change in external osmotic pressure, turgor pressure, membrane strain, internal osmolality and/or concentration of specific signal molecule . We also evaluate the molecular basis for osmosensing by reviewing the unique structural features of known osmoregulated transport systems. Appl Microbiol Biotechnol, 1998 Jul, 50(1), 1 - 15 New aspects of genes and enzymes for beta-lactam antibiotic biosynthesis; Martin JF; Penicillins, cephalosporins and cephamycins are peptide antibiotics synthesized by condensation of L-alpha-aminoadipic acid, L-cysteine and L-valine to form the tripeptide delta(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (Aad-Cys-Val) by a non-ribosomal peptide synthetase . The genes pcbAB and pcbC, common to all penicillin and cephalosporin producers, that encode the Aad-Cys-Val synthetase and isopenicillin N (IPN) synthase respectively, have been cloned and the encoded enzymes studied in detail . The IPN synthase has been crystallized and its active center identified, providing evidence for the molecular mechanism of cyclization of the tripeptide Aad-Cys-Val to isopenicillin N . The late genes of the penicillin and cephalosporin pathways have also been characterized although some of the molecular mechanisms catalyzed by the encoded enzymes (e.g . IPN acyltransferase) are still obscure . In cephamycin-producing organisms, biosynthesis of the alpha-aminoadipic acid precursor proceeds in two steps catalyzed by lysine 6-aminotransferase and piperideine-6-carboxylic acid dehydrogenase . The gene lat for the first of these enzymes is located in the cephamycin gene cluster, providing an interesting example of association of genes encoding enzymes for the formation of a precursor with genes involved in assembly of the antibiotics . Novel enzymes involved in methoxylation at C-7 and carbamoylation at C-3' of the cephem nucleus were isolated from Nocardia lactamdurans and Streptomyces clavuligerus . The methoxylation system is encoded by two linked genes cmcI-cmcJ and their products (proteins P7 and P8) form a complex that is required for hydroxylation at C-7 and for the subsequent methylation of the 7-hydroxycephem derivative to form the methoxyl group . Carbamoylation at the C-3'-hydroxyl group of the cephem nucleus is catalyzed by a specific carbamoyltransferase encoded by the gene cmcH . Finally, genes for a beta-lactamase (bla), a penicillin-binding protein (pbp) and a transmembrane protein (cmcT) that appears to be involved in cephamycin exportation, are clustered together with the biosynthetic genes in the cephamycin clusters of S . clavuligerus and N . lactamdurans . Availability of the cloned genes allows metabolic engineering of the beta-lactam biosynthetic pathways such as a channelling precursors and directed removal of bottlenecks in the beta-lactam biosynthetic pathways . Several new beta-lactam antibiotics have been discovered in gram-positive and gram-negative bacteria that will provide new genes for combinatorial synthesis of new molecules. Biochemistry, 1998 Aug 25, 37(34), 11762 - 70 Topography of the interaction of HPr(Ser) kinase with HPr; Zhu PP et al.; The phosphocarrier protein, HPr, from Gram-positive organisms and mycoplasmas is a substrate for an ATP-dependent kinase that phosphorylates serine 46 . In Gram-negative organisms, the corresponding HPr is not phosphorylated on serine 46 and the ATP-dependent kinase is absent . To determine the specificity requirements for phosphorylation of Mycoplasma capricolum HPr, a chimera in which residues 43-57 were replaced by the Escherichia coli sequence was constructed . The chimeric protein folded properly, but was not phosphorylated on either serine 46 or histidine 15 . A dissection of the region required for phosphorylation specificity was carried out by further mutagenesis . The deficiency in phosphorylation at histidine 15 was localized primarily to the region including residues 51-57 . Activity studies revealed that residues 48, 49, and 51-53 are important for recognition of M . capricolum HPr by its cognate HPr(Ser) kinase . The characteristics of this region suggest that the kinase-HPr interaction occurs mainly through a hydrophobic region . Molecular modeling comparisons of M . capricolum HPr and the chimeric construct provided a basis for interpreting the results of the activity assays. Gene, 1998 Jul 30, 215(2), 405 - 13 Codon usage in highly expressed genes of Haemophillus influenzae and Mycobacterium tuberculosis: translational selection versus mutational bias; Pan A et al.; Biases in the codon usage and base compositions at three codon sites in different genes of A+T-rich Gram-negative bacterium Haemophillus influenzae and G+C-rich Gram-positive bacterium Mycobacterium tuberculosis have been examined to address the following questions: (1) whether the synonymous codon usage in organisms having highly skewed base compositions is totally dictated by the mutational bias as reported previously (Sharp, P.M., Devine, K.M., 1989 . Codon usage and gene expression level in Dictyostelium discoideum: highly expressed genes do 'prefer' optimal codons . Nucleic Acids Res . 17, 5029-5039), or is also controlled by translational selection; (2) whether preference of G in the first codon positions by highly expressed genes, as reported in Escherichia coli (Gutierrez, G., Marquez, L., Marin, A., 1996 . Preference for guanosine at first codon position in highly expressed Escherichia coli genes . A relationship with translational efficiency . Nucleic Acids Res . 24, 2525-2527), is true in other bacteria; and (3) whether the usage of bases in three codon positions is species-specific . Result presented here show that even in organisms with high mutational bias, translational selection plays an important role in dictating the synonymous codon usage, though the set of optimal codons is chosen in accordance with the mutational pressure . The frequencies of G-starting codons are positively correlated to the level of expression of genes, as estimated by their Codon Adaptation Index (CAI) values, in M . tuberculosis as well as in H . influenzae in spite of having an A+T-rich genome . The present study on the codon preferences of two organisms with oppositely skewed base compositions thus suggests that the preference of G-starting codons by highly expressed genes might be a general feature of bacteria, irrespective of their overall G+C contents . The ranges of variations in the frequencies of individual bases at the first and second codon positions of genes of both H . influenzae and M . tuberculosis are similar to those of E . coli, implying that though the composition of all three codon positions is governed by a selection-mutation balance, the mutational pressure has little influence in the choice of bases at the first two codon positions, even in organisms with highly biased base compositions. Microb Pathog, 1998 Aug, 25(2), 101 - 9 Properties of repeat domain found in a novel protective antigen, SpaA, of Erysipelothrix rhusiopathiae; Makino S et al.; Erysipelothrix rhusiopathiae is a small gram-positive rod bacterium that causes erysipelas in swine and a variety of diseases in other animals and humans . Although live-attenuated or bacterin vaccines are effective in protecting against erysipelas, the genetic construction of their active antigen has not been identified . To clarify the surface antigen(s) involved in protective and arthritic response, using monoclonal antibody I2A against the surface proteins of E . rhusiopathiae, we identified a protective antigen, which consists of 606 amino acids . Analysis of deletion derivatives of the gene, spaA(surface protective antigen), showed that the SpaA protein binds tightly to the bacterial cell surface via eight repeat units with a GW-module consisting of 20 amino acids at the C-terminus . Although DeltaSpaA lacking their repeat units lost its ability to induce protection against E . rhusiopathiae infection, intact SpaA protein showed the protection . We conclude that the presence of repeat units is essential both for the binding of SpaA to the bacterial cell surface and for protection . We believe that the repeat region at the C-terminus should be a candidate for a subunit vaccine against erysipelas . Int J Radiat Biol, 1998 Aug, 74(2), 249 - 53 High sensitivity of Deinococcus radiodurans to photodynamically-produced singlet oxygen; Schafer M et al.; PURPOSE: To study the sensitivity of two bacterial cell systems to photodynamic treatment and X-ray irradiation as part of a project to establish efficient procedures for waste water disinfection . MATERIALS AND METHODS: Stationary-phase cells of Deinococcus radiodurans (Gram-positive) and Escherichia coli (Gram-negative) were exposed to visible light in a buffer solution containing up to 5 microg/ml sensitizer rose bengal (RB) and to X-rays at dose rates of 32.8 Gy/min or 14.6 Gy/min, respectively . RESULTS: Survival of both cell types decreased with increasing exposure time to visible light and increasing concentration of RB, and therefore with an increase in singlet oxygen production . Surprisingly, D . radiodurans, the most resistant cell system to ionizing radiation, was more sensitive to photodynamic treatment than E . coli by about a factor of 100 . CONCLUSIONS: The main target of singlet oxygen reaction is the cell membrane . The repair of such damage in D . radiodurans is less effective than in E . coli. Proc Natl Acad Sci U S A, 1998 Aug 18, 95(17), 10078 - 82 A peptidoglycan recognition protein in innate immunity conserved from insects to humans; Kang D et al.; Innate nonself recognition must rely on common structures of invading microbes . In a differential display screen for up-regulated immune genes in the moth Trichoplusia ni we have found mechanisms for recognition of bacterial cell wall fragments . One bacteria-induced gene encodes a protein that, after expression in the baculovirus system, was shown to be a peptidoglycan recognition protein (PGRP) . It binds strongly to Gram-positive bacteria . We have also cloned the corresponding cDNA from mouse and human and shown this gene to be expressed in a variety of organs, notably organs of the immune system-i.e., bone marrow and spleen . In addition, purified recombinant murine PGRP was shown to possess peptidoglycan affinity . From our results and the sequence homology, we conclude that PGRP is a ubiquitous protein involved in innate immunity, conserved from insects to humans. Syst Appl Microbiol, 1998 Jun, 21(2), 306 - 14 Arthrobacter, Brachybacterium and Planococcus isolates identified from antarctic sea ice brine . Description of Planococcus mcmeekinii, sp . nov; Junge K et al.; Three facultative psychrophilic Gram-positive bacterial strains were isolated from brine samples from the sea ice community in Antarctica . All strains were coccoid to rod-shaped and exhibited broad salinity and temperature ranges for growth . The three strains were subjected to 16S rDNA sequencing and subsequent phylogenetic analysis . All possess unique 16S rDNA sequences indicating they are new, previously unreported organisms . Phylogenetic analyses coupled with phenotypic characterization indicated that one of the strains is most closely related to the low mol% G + C genus Planococcus for which a new species, P . mcmeekinii, is proposed . The two other strains are members of the high mol% G + C Gram-positive bacteria and most closely related to the genera Arthrobacter and Brachybacterium . This study reports the first phylogenetic evidence that Gram-positive bacteria reside in the marine sea ice brine. Carbohydr Res, 1998 Jan, 306(1-2), 305 - 14 Structural studies of the major polysaccharide in the cell wall of Renibacterium salmoninarum; Sorum U et al.; The galactose-rich polysaccharide (GPS) in the cell wall of the Gram-positive bacterium Renibacterium salmoninarum, the causative agent in of bacterial kidney disease (BKD) of salmonids, has been studied by sugar and methylation analysis, partial acid hydrolysis, Smith degradation, FABMS, and 1H and 13C NMR spectroscopy . The data show that the GPS has a heptasaccharide repeating unit with the following structure: alpha-D-Rhap-(1-->3)-alpha-L-FucpNAc-(1-->)-beta-D-GlcpNAc 1 decreases 2 -->3)-beta-D-Galf-(1-->6)-beta-D-Galf-(1-->3)-beta-D-Galf -(1-->6) -beta-D-Galf-(1-->. J Antimicrob Chemother, 1998 Jun, 41 Suppl D, 57 - 64 Neutropenic infections: a review of the French Febrile Aplasia Study Group trials in 608 febrile neutropenic patients; Marie JP et al.; From 1986 to 1992, the Febrile Aplasia Study Group conducted a series of studies involving severely neutropenic patients . The average duration of neutropenia was 21 days, following chemotherapy for leukaemia, or chemotherapy/radiotherapy as part of a conditioning regimen for autologous or allogeneic bone marrow transplantation . A total of 591 evaluable febrile episodes were randomized to treatment with either ceftazidime 3 g daily + amikacin (the reference regimen; n=246), ceftazidime alone (n=98), ceftazidime + vancomycin (n=77), ceftazidime + ciprofloxacin (n=64) or piperacillin/tazobactam + amikacin (n=106) . Only three patients treated with the reference dose of ceftazidime died or suffered serious morbidity from infections caused by Gram-negative bacteria . Piperacillin/tazobactam + amikacin was the only antibiotic regimen to have an effect significantly different from the reference regimen . Piperacillin/tazobactam + amikacin produced a higher rate of defervescence at 72 h (P=0.003), fewer days of fever (P < 0.001), fewer superinfections (P=0.018), a less frequent requirement for addition of vancomycin (P=0.01) and a higher incidence of treatment judged to be a 'complete success' (enduring defervescence without a change in antibiotics) (P=0.04) . Despite the improved control of Gram-positive microorganisms, the infection-related death rate remained unchanged from 1987 to 1992 . An increase in disseminated aspergillosis compensated for the reduction in lethal Gram-positive septicaemia. J Antimicrob Chemother, 1998 Jun, 41 Suppl D, 43 - 9 Beta-lactam/beta-lactamase inhibitor combinations: pharmacodynamic considerations and possible role in the management of bacterial infections in the neutropenic host; Okereke C et al.; Morbidity and mortality in febrile neutropenic patients result mainly from complications attributable to infectious diseases . Both Gram-negative and Gram-positive bacterial infections have been implicated . The use of antibiotics in combating bacterial infections has been hampered by production by many bacterial pathogens of beta-lactamases that render them resistant to beta-lactam antibiotics . Since susceptibility to the beta-lactam appears crucial in attaining a clinical response in Gram-negative bacteraemia in febrile neutropenic patients, regimens that inhibit the activity of beta-lactamases are desirable . Although many beta-lactamase inhibitors, such as tazobactam, can result in irreversible inhibition of bacterial beta-lactamase in vitro, careful selection of dosage, as well as testing in models of infection mimicking that in patients, is required . Experimental studies in in-vitro models of infection that mimic conditions of absent host response, show that tazobactam restores the activity of piperacillin against beta-lactamase-producing bacteria . Optimal dosage regimens of beta-lactamase inhibitors will provide mean concentrations of beta-lactamase inhibitor at or above those used in in-vitro testing. J Antimicrob Chemother, 1998 Jun, 41 Suppl D, 13 - 24 Science and pragmatism in the treatment and prevention of neutropenic infection; Klastersky J; The following aspects of the management of patients with granulocytopenia and fever are reviewed in this article: adaptation of initial antibiotic regimens to the recent changes in the most common causative pathogens (namely a change from Gram-negative bacteria to Gram-positive bacteria and fungi); subsequent modifications of the empirically administered treatments; improvement of the host's defence by reducing the duration of neutropenia; and indications for out patient therapy of febrile episodes. Appl Environ Microbiol, 1998 Aug, 64(8), 3059 - 62 Estimation of the state of the bacterial cell wall by fluorescent In situ hybridization; Bidnenko E et al.; Fluorescent in situ hybridization (FISH) is now a widely used method for identification of bacteria at the single-cell level . With gram-positive bacteria, the thick peptidoglycan layer of a cell wall presents a barrier for entry of horseradish peroxidase (HRP)-labeled probes . Therefore, such probes do not give any signal in FISH unless cells are first treated with enzymes which hydrolyze the peptidoglycan . We explored this feature of FISH to detect cells which have undergone permeabilization due to expression of autolytic enzymes . Our results indicate that FISH performed with HRP-labeled probes provides a sensitive method to estimate the states of cell walls of individual gram-positive bacteria. J Immunoassay, 1998 May-Aug, 19(2-3), 95 - 111 The detection of pyrogens in blood products using an ex vivo whole blood culture assay; Pool EJ et al.; Induction of interleukin-6 (IL-6) secretion by whole blood cultures (WBC) was used as an in vitro assay system for pyrogen-induced inflammatory reactions . The assay system was very sensitive to Eschericia coli (E coli) endotoxin (< 10 pg/ml) . The potential pyrogenic effects of human serum albumin (HSA), Fibronectin (Fn) and stabilised human serum (SHS) solutions were analyzed using this system . None of the products assayed had an effect on the sensitivity of the WBC assay . Spike recovery studies with isolated endotoxin, gram positive and gram negative bacteria showed that none of the products had an effect on the spike recovery of these pyrogenic substances . Good correlations were found between the WBC assay and the rabbit assay for pyrogens for all the production batches tested . When these samples were analysed by the limulus amoebocyte lysate (LAL) assay, the LAL test gave anomalous results for 1 out of the 22 production batches tested . This batch gave a false negative result on the LAL assay and might be indicative of the inability of the LAL assay to detect pyrogens other than endotoxin. J Immunol Methods, 1998 Mar 15, 212(2), 169 - 85 A rapid assay of endotoxin in whole blood using autologous neutrophil dependent chemiluminescence; Romaschin AD et al.; A rapid (30 min) whole blood assay for the detection of lipopolysaccharide (LPS) is described . This chemiluminescent (CL) assay utilizes the CR1 and CR3 receptor-induced oxidant production of polymorphonuclear leucocytes as a detection platform . The differential priming of neutrophils in whole blood by LPS-antibody complexes allows the specificity of the assay to be achieved . Oxidant released in response to complement opsonized zymosan results in luminol oxidation and subsequent light emission . This is dependent on heat labile putative complement proteins in the plasma . The assay consists of a control which measures baseline whole blood neutrophil oxidant production . The test assay contains murine monoclonal IgM antibody against the Lipid A epitope of LPS and measures the enhanced chemiluminescent response of the neutrophils in the presence of LPS-antibody complexes . Maximal sensitivity of the CL assay is dependent upon optimal antigen-antibody equivalence and duration of pre-incubation with the whole blood sample . The quantification of LPS is possible by inclusion of a positive control containing a maximally reactive LPS dose (800 pg/ml Escherichia coli 055:B5 LPS at an antibody concentration of 0.8 microg/assay) . The CL assay is insensitive to variations in patient neutrophil concentration over a minimum range of 0.5 to 20 x 10(9) cells/l . The CL assay is widely reactive with the LPS of many strains of gram negative bacteria but not with the cell wall products of gram positive bacteria or Candida and Aspergillus . In comparison to acid extraction chromogenic LAL, the CL assay demonstrates superior recovery precision and accuracy in in vitro studies . This was reproducible over a wide range of LPS concentrations (0.017-1.6 EU/ml or 20-2000 pg/ml) . This assay may be a clinically useful tool for the diagnosis of infection or endotoxin in patients. Int J STD AIDS, 1998 Jun, 9(6), 350 - 3 Chlamydia trachomatis: probable cause of prostatitis; Ostaszewska I et al.; Seventy-eight men with symptoms of chronic or subacute prostatitis were enrolled . Investigations for the presence of Chlamydia trachomatis in urethral swabs were carried out . The expressed prostatic secretions were additionally examined for Mycoplasma hominis, Ureaplasma urealyticum, Gardnerella vaginalis, other gram-negative and gram-positive bacteria, Trichomonas vaginalis, yeast-like fungi and leucocyte count . Furthermore, all patients were evaluated for the presence of serum anti-chlamydial IgG antibodies . Signs of inflammation on the basis of the count of leucocytes per hpf in the prostatic secretions were detected in 42 patients (group I) . Prostatodynia was found in the remaining 36 men (group II) . In group I, chlamydial antigen was detected in the urethra and expressed prostatic secretions (EPS) in 6 (14.3%) and 9 (21.4%) patients, respectively . No evidence of current chlamydial infection was found in group II . The presence of serum anti-chlamydial IgG antibodies was demonstrated in 13/42 (30.9%) patients with prostatitis and in 3/36 (8.3%) patients with prostatodynia (P < 0.01) . The results suggest that chlamydia may be one of the causative agents of chronic prostatitis. Leuk Lymphoma, 1998 Jun, 30(1-2), 193 - 7 Incidence of sepsis after peripheral blood progenitor cells transplantation: analysis of 86 consecutive hemato oncological patients; Salutari P et al.; The incidence of documented infections after autologous peripheral blood progenitor cells transplantation (PBPCT) was retrospectively evaluated in 86 consecutive patients (47 males 39 females; median age 36 years, range, 18-63) treated in our institution; 83 patients had refractory hematological malignancies (40 non-Hodgkin's lymphoma, 19 Hodgkin's disease, 17 multiple myeloma, 7 acute myeloblastic leukemia) and 3 had solid tumors (1 rabdomyosarcoma, 1 neuroblastoma, 1 osteosarcoma) . All patients developed fever after transplantation lasting a median of 2 days (range 1-17); 20 instances of documented sepsis developed in 17 patients (19.7%) . Gram positive microorganisms were implicated in all but 4 cases . There were no fatalities directly due to infections and no correlation was found between the risk of infection and reaching PMN > 0, 1 x 10(9)/L, PMN > 0.5 x 10(9)/L . In addition no specific risk factors related to age, disease, conditioning regimen, use of central venous catheter (CVC), type of transplant, and isolation measures were identified. Mol Microbiol, 1998 Jun, 28(5), 905 - 16 The telomeres of Streptomyces chromosomes contain conserved palindromic sequences with potential to form complex secondary structures; Huang CH et al.; The chromosomes of the gram-positive soil bacteria Streptomyces are linear DNA molecules, usually of about 8Mb, containing a centrally located origin of replication and covalently bound terminal proteins (which are presumably involved in the completion of replication of the telomeres) . The ends of the chromosomes contain inverted repeats of variable lengths . The terminal segments of five Streptomyces chromosomes and plasmids were cloned and sequenced . The sequences showed a high degree of conservation in the first 166-168bp . Beyond the terminal homology, the sequences diverged and did not generally cross-hybridize . The homologous regions contained seven palindromes with a few nucleotide differences . Many of these differences occur in complementary pairs, such that the palindromicity is preserved . Energy-optimized modelling predicted that the 3' strand of the terminal palindromes can form extensive hairpin structures that are similar to the 3' ends of autonomous parvovirus genomes . Most of the putative hairpins have a GCGCAGC sequence at the loop, with the potential to form a stable single C-residue loop closed by a sheared G:A pairing . The similarity between the terminal structures of the Streptomyces replicons and the autonomous parvoviral genomes suggests that they may share some structural and/or replication features. Mol Microbiol, 1998 Jun, 28(5), 865 - 74 PRD--a protein domain involved in PTS-dependent induction and carbon catabolite repression of catabolic operons in bacteria; Stulke J et al.; Several operon-specific transcriptional regulators, including antiterminators and activators, contain a duplicated conserved domain, the PTS regulation domain (PRD) . These duplicated domains modify the activity of the transcriptional regulators both positively and negatively . PRD-containing regulators are very common in Gram-positive bacteria . In contrast, antiterminators controlling beta-glucoside utilization are the only functionally characterized members of this family from gram-negative bacteria . PRD-containing regulators are controlled by PTS-dependent phosphorylation with different consequences: (i) In the absence of inducer, the phosphorylated EIIB component of the sugar permease donates its phosphate to a PRD, thereby inactivating the regulator . In the presence of the substrate, the regulator is dephosphorylated, and the phosphate is transferred to the sugar, resulting in induction of the operon . (ii) In gram-positive bacteria, a novel mechanism of carbon catabolite repression mediated by PRD-containing regulators has been demonstrated . In the absence of PTS substrates, the HPr protein is phosphorylated by enzyme I at His-15 . This form of HPr can, in turn, phosphorylate PRD-containing regulators and stimulate their activity . In the presence of rapidly metabolizable carbon sources, ATP-dependent phosphorylation of HPr at Ser-46 by HPr kinase inhibits phosphorylation by enzyme I, and PRD-containing regulators cannot, therefore, be stimulated and are inactive . All regulators of this family contain two copies of PRD, which are functionally specialized in either induction or catabolite repression. Pediatr Radiol, 1998 Jul, 28(7), 521 - 3 Percutaneous gastrostomy tube placement in patients with ventriculoperitoneal shunts; Sane SS et al.; OBJECTIVE: The purpose of this study is to determine the risk of CNS and/or peritoneal infection in children with ventriculoperitoneal shunts in whom a percutaneous gastrostomy tube is placed . MATERIALS AND METHODS: We placed 205 gastrostomy or gastrojejunostomy tubes from January of 1991 to December 1996 . Twenty-three patients (10 boys, 13 girls) had ventriculoperitoneal shunts at the time of placement . All shunts were placed at least 1 month prior to placement of the gastrostomy tube . The patients ranged in age from 8 months to 16 years with a mean age of 6 years, 9 months . Patient weight ranged from 2 kg to 60 kg . All 23 children required long-term nutritional support due to severe neurologic impairment . No prophylactic antibiotics were given prior to the procedure . Of the patients, 21/23 had a 14-F Sacks-Vine gastrostomy tube with a fixed terminal retention device inserted, using percutaneous fluoroscopic antegrade technique . Two of the 23 patients had a Ross 14-F Flexi-flo gastrostomy tube which required a retrograde technique due to a small caliber esophagus in these children . RESULTS: All 23 children had technically successful placements of percutaneous gastrostomy (7) or gastrojejunostomy (16) tubes . Of the children, 21/23 (91%) had no complications from the procedure . Two of 23 (9%) patients demonstrated signs of peritonitis after placement of their gastrostomy tubes and subsequently had shunt infections . In both, children CSF culture grew gram-positive cocci . The antegrade technique was used in both children who developed peritonitis . CONCLUSION: Our study indicates children with ventriculoperitoneal shunts who undergo percutaneous gastrostomy are at greater risk for infection and subsequent shunt malfunction . Therefore, we recommend prophylactic antibiotic therapy to cover for skin and oral flora. J Biomed Mater Res, 1998 Sep 5, 41(3), 349 - 58 Adhesion of different bacterial strains to low-temperature plasma-treated sutures; Yousefi Rad A et al.; In this study, five different bacteria with their different strains were isolated and characterized . Contact angles were measured by a captive-bubble technique . Surface-free energies were calculated from the contact angles . Hydrophobicities also were evaluated by rho-xylene adhesion . The zeta potentials and surface charges of the bacteria were obtained . The contact angles of the gram-positive bacteria and gram-negative bacteria were within the range of 48 degrees-69 degrees and 43.5 degrees-55 degrees, respectively, while corresponding surface-free energies were in the limits of 45.4-51.6 erg/cm-2 and 51.7-61.8 erg/cm-2, respectively . The rho-xylene adhesions were parallel to hydrophobicities defined by contact angles, and 32.2-80.3% and 2.3-36.6% for the gram-positive bacteria and gram-negative bacteria, respectively . The zeta potentials for these bacteria were from -650.2 to +17.5 mV and from -159.6 to -6.0 mV, respectively . Most of the bacteria were negatively charged, except the CNS-2 and CPS-1 strains . In the second part of the study, attachment of these bacteria to Vicryl sutures and their DMAEMA and AAc plasma-treated forms were investigated . Hydrophobic bacteria attached more to hydrophobic Vicryl sutures . Both plasma treatments caused significant drops in bacterial attachment in most cases . Effects of AAc plasma treatment were more pronounced. Cancer, 1998 Jun 15, 82(12), 2449 - 58 How should imipenem-cilastatin be used in the treatment of fever and infection in neutropenic cancer patients? Raad II, Abi-Said D, Rolston KV, Karl CL, Bodey GP. BACKGROUND: Imipenem-cilastatin (referred to hereafter as imipenem) is administered at different doses as monotherapy or with other agents . Limited comparisons of the alternatives exist . The authors compared the efficacy and safety of several imipenem-containing regimens (ICRs) to determine the appropriate dose and the need for combination therapy . METHODS: Between 1985 and 1994, febrile neutropenic patients were given ICRs according to the same methodology on prospective trials at a referral cancer center . The ICRs were high dose imipenem (HIP), high dose imipenem and amikacin (HIPA), high dose imipenem and vancomycin (HIPV), and low dose imipenem and vancomycin (LIPV) . RESULTS: The overall response rates were comparable (70-77%) . There was a univariate trend toward better response among patients with pneumonia and documented infections with unidentified organisms who received HIPV versus LIPV (P=0.06), as well as a significantly better response among patients with gram positive infections who received HIPV versus HIP (P=0.02) and HIPA (P=0.002) . HIPV was a more effective treatment for documented infections with identified organisms (P=0.05) and bloodstream infections (P=0.04) than HIP; there was a univariate trend toward better response among patients inf