Int J Food Microbiol, 1998 Mar 3, 40(1-2), 27 - 34 Phage typing combined with pulsed-field gel electrophoresis and random amplified polymorphic DNA increases discrimination in the epidemiological analysis of Salmonella enteritidis strains; Laconcha I et al.; Phage typing (PT) combined with pulsed-field gel electrophoresis (PFGE) and a random amplified polymorphic DNA (RAPD) fingerprinting method was used to characterize Salmonella enteritidis strains . Twenty-four epidemiologically unrelated isolates, sampled from diverse ecological niches and fifteen isolates from four well-defined outbreaks of foodborne gastroenteritis, were studied . Seven phage types, with a predominance of PT 4 (63% of isolates), were observed when analysing the epidemiologically unrelated group . PT 4 was detected in all of the ecological niches studied, including food and fecally polluted river and beach water . The discriminatory power for phage typing, the average probability that the typing system will assign a different type to two unrelated strains randomly sampled in the microbial population, was 0.62 . Ten PFGE pattern types were obtained with Xba I restriction endonuclease enzyme among the unrelated isolates; thirteen isolates belonged to PFGE pattern type 1 and the rest of the PFGE types were assigned to one or two isolates . The Dice coefficient clustered the similarities of the PFGE patterns between 80-100% . PFGE showed a discriminatory power of 0.72 . Five clearly distinct RAPD patterns were observed with the OPS-19 oligonucleotide, but the discrimination obtained was low (0.46) . The combination of the three typing methods increased the number of types to seventeen, giving high discrimination (0.92) . Seven of the isolates recovered from various ecological niches belonged to the combination PT 4/PFGE 1/RAPD A and other combinations were unique or included only two strains . The four epidemiologically well-defined foodborne outbreaks were associated with the PT 4 phage type . In two of the outbreaks, other phage types (PT 7a and RDNC) were also observed in two isolates . Most of the isolates belonging to the foodborne outbreaks had an identical PFGE pattern (PFGE pattern type 1), but a difference in a restriction band was observed in an isolate belonging to an outbreak . Two RAPD patterns were observed in the outbreaks; RAPD pattern type A was detected in three of the four outbreaks . When the combined typing method was applied to the study, high concordance was observed and most of the outbreak strains belonged to the combination PT 4/PFGE 1/RAPD A . It is concluded that the combination of phage type with PFGE and RAPD provides a powerful discriminatory tool for the epidemiological analysis of unrelated and related strains of S . enteritidis. Int J Food Microbiol, 1998 Mar 3, 40(1-2), 1 - 8 Prevalence of Salmonella in poultry carcasses and their products in Belgium; Uyttendaele MR et al.; During four subsequent years (1993 until 1996), a study was conducted to isolate and characterize Salmonella in poultry carcasses and their products sold in Belgium . This was a semiquantitative approach (absence per 100 cm2 or 25 cm2 or 25 g and absence per cm2 or g) to elucidate the degree of Salmonella contamination of the poultry . Serotyping was performed during the last two and a half years . Samples were frozen and kept at -20 degrees C before analysis . This may have influenced the number of Salmonella recovered . No improvement in the rate of contamination was noted during these four years, with rates being 19.4% for 1993, 24.1% for 1994, 21.9% for 1995 and 36.7% for 1996 . A 100% increase of Salmonella-positive samples resulted from cutting up the carcasses into individual parts . Chicken parts were more often contaminated with Salmonella than turkey parts . Boiling hen carcasses showed the highest Salmonella contamination . Prepared poultry, chicken parts and boiling hen carcasses are sometimes associated with Salmonella contamination levels of > 1 cfu/cm2 or g . In 1996, respectively 15.1%, 4.2% and 4.2% of highly contaminated samples (> 1 cfu/cm2 or g) were found for these product groups . The predominant three serotypes were S . enteritidis (16.3%), S . hadar (15.5%) and S . virchow (14.1%) . S . newport was frequently isolated from turkey products. J Clin Microbiol, 1998 Apr, 36(4), 971 - 4 Epidemiological analysis of Salmonella enteritidis isolates from humans and broiler chickens in Thailand by phage typing and pulsed-field gel electrophoresis; Boonmar S et al.; To determine the phage types (PT) of Salmonella enteritidis found in Thailand and to clarify the potential for human infection by S . enteritidis in broiler chicken meat, human and poultry isolates taken from Thailand between 1990 and 1997 were phage typed and analyzed by pulsed-field gel electrophoresis (PFGE) . Ten different PT were found among the 302 isolates phage typed, with PT 4 being the most frequent in human (73.9%) and poultry (76.2%) isolates, followed by PT 1 (8.0%), 8 (3.6%), and 7a (2.2%) in human isolates and by PT 7a (4.9%), 1 (3.7%), and 12 (2.4%) in poultry isolates . Of the 53 isolates analyzed by PFGE, 45 showed an indistinguishable pattern (pattern A) by BlnI-digested PFGE and the other 8 isolates showed a very similar pattern that differed by only a few bands . These results indicate the spread of a genetically identical clone of S . enteritidis in humans and poultry in Thailand. Clin Cardiol, 1998 May, 21(5), 368 - 70 Successful conservative treatment of nontyphoid salmonella endocarditis involving a bioprosthetic valve; Goerre S et al.; We report a first case of Salmonella enteritidis endocarditis involving a bioprosthetic aortic valve . Despite additional native tricuspid valve involvement, the clinical course was favorable using an antibiotic regimen of ciprofloxacin and netilmicin . Although Salmonella prosthetic valve endocarditis is considered an indication for surgical replacement of the prosthesis, this case indicates that prolonged treatment with fluoroquinolones may be an alternative provided that the hemodynamic situation is stable. Epidemiol Infect, 1998 Mar, 120(2), 129 - 38 Risk factors for typhoid fever in an endemic setting, Karachi, Pakistan; Luby SP et al.; We conducted a study to evaluate risk factors for developing typhoid fever in a setting where the disease is endemic in Karachi, Pakistan . We enrolled 100 cases with blood culture-confirmed Salmonella typhi between July and October 1994 and 200 age-matched neighbourhood controls . Cases had a median age of 5.8 years . In a conditional logistic regression model, eating ice cream (Odds ratio {OR} = 2.3; 95% confidence interval {CI} 1.2-4.2, attributable risk {AR} = 36%), eating food from a roadside cabin during the summer months (OR = 4.6, 95% CI 1.6-13.0; AR = 18%), taking antimicrobials in the 2 weeks preceding the onset of symptoms (OR = 5.7, 95% CI 2.3-13.9, AR = 21%), and drinking water at the work-site (OR = 44.0, 95% CI 2.8-680, AR = 8%) were all independently associated with typhoid fever . There was no difference in the microbiological water quality of home drinking water between cases and controls . Typhoid fever in Karachi resulted from high-dose exposures from multiple sources with individual susceptibility increased by young age and prior antimicrobial use . Improving commercial food hygiene and decreasing unnecessary antimicrobial use would be expected to decrease the burden of typhoid fever. Epidemiol Infect, 1998 Mar, 120(2), 125 - 8 National outbreak of Salmonella senftenberg associated with infant food; Rushdy AA et al.; Eight cases of Salmonella senftenberg infection in infants were identified in the first half of 1995 in England, five were indistinguishable S . senftenberg strains . A case-control study showed an association between illness and consumption of one brand of baby cereal (P = 0.03) . The cereal manufacturer reported isolating S . senftenberg in June 1994 from an undistributed cereal batch . Outbreak strains and the cereal strain were all plasmid-free in contrast to other human isolates of S . senftenberg in the same period . Changes in the production process were implemented to prevent further contamination . Surveillance centres should strengthen the detection and investigation of outbreaks of gastrointestinal infection in susceptible groups, especially young children . In this outbreak, the study of only five cases led to identification of the vehicle of infection . Even when few cases are reported, epidemiological investigation in conjunction with molecular typing may lead to public health action which prevents continuing or future outbreaks. Antimicrob Agents Chemother, 1998 May, 42(5), 1288 - 9 Tetracycline resistance in Salmonella enterica subsp . enterica serovar Dublin; Frech G et al.; The 47-kbp plasmid pGFT1 from Salmonella enterica subsp . enterica serovar Dublin mediated tetracycline resistance via a tet(A) gene located on an integrated copy of a Tn1721-analogous transposon . The integration site of the transposon was located within the reading frame of a fip gene . Plasmid pGFT1 was shown to be conjugative and to be able to replicate and express tetracycline resistance in Escherichia coli. Nature, 1998 May 7, 393(6680), 79 - 82 Salmonella typhi uses CFTR to enter intestinal epithelial cells; Pier GB et al.; Homozygous mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis (CF) . In the heterozygous state, increased resistance to infectious diseases may maintain mutant CFTR alleles at high levels in selected populations . Here we investigate whether typhoid fever could be one such disease . The disease is initiated when Salmonella typhi enters gastrointestinal epithelial cells for submucosal translocation . We found that S . typhi, but not the related murine pathogen S . typhimurium, uses CFTR for entry into epithelial cells . Cells expressing wild-type CFTR internalized more S . typhi than isogenic cells expressing the most common CFTR mutation, a phenylalanine deleted at residue 508 (delta508) . Monoclonal antibodies and synthetic peptides containing a sequence corresponding to the first predicted extracellular domain of CFTR inhibited uptake of S . typhi . Heterozygous deltaF508 Cftr mice translocated 86% fewer S . typhi into the gastrointestinal submucosa than wild-type Cftr mice; no translocation occurred in deltaF508 Cftr homozygous mice . The Cftr genotype had no effect on the translocation of S . typhimurium . Immunoelectron microscopy revealed that more CFTR bound to S . typhi in the submucosa of Cftr wild-type mice than in deltaF508 heterozygous mice . We conclude that diminished levels of CFTR in heterozygotes may decrease susceptibility to typhoid fever. Genetika, 1998 Feb, 34(2), 308 - 12 {Genotoxic effects of metabolic derivatives of the new drug phosphabenzide}; Il'inskaia ON et al.; Genotoxic action of four possible metabolites of the new tranquilizer phosphabenzide (acetylphosphabenzide, diphenylphosphinylacetic acid, phosphabenzide hydrazone with pyruvic acid, bis-1,2-(diphenylphosphinylacetyl)hydrazine) has been studied . These metabolites belong to slightly toxic phosphororganic compounds . The Ames Salmonella/microsomes tests performed on strains TA100 and TA98 showed that of these compounds only acetylphosphabenzide possessed mutagenic action . Metabolic activation of liver microsomes decreased the mutagenic effect . The mechanism of action of acetylphosphabenzide is likely to involve the formation of acetylhydrazine, capable of producing active electrophiles attacking DNA. Electrophoresis, 1998 Apr, 19(4), 569 - 72 Chromosomal rearrangements in enteric bacteria; Sanderson KE et al.; Early genetic studies showed conservation of gene order in the enteric bacteria . Two recent methods using pulsed field gel electrophoresis (PFGE) to determine the physical map of the genome are: (i) partial digestion with the endonuclease I-CeuI, which digests the DNA of bacteria in the rrn operon for rRNA (ribosomal RNA), thus establishing the "rrn genomic skeleton" (the size in kbp of the intervals between rRNA operons); (ii) analysis of XbaI and B1nI sites within Tn10 insertions in the chromosome . The order of I-CeuI fragments, which is ABCDEFG in S . typhimurium LT2 and E . coli K-12, was found to be conserved in most Salmonella species, most of which grow in many hosts (host-generalists) . However, in S . typhi, S . paratyphi C, S . gallinarum, and S . pullorum, species which are host-specialized, these fragments are rearranged, due to homologous recombination between the rrn operons, resulting in translocations and inversions . Inversions and translocations not involving the rrn operons are seldom detected except for inversions over the TER (termination of replication) region . Additive genetic changes (due to lateral transfer resulting in insertion of nonhomologous DNA) have resulted in "loops" containing blocks of DNA which provide new genes to specific strains, thus driving rapid evolution of new traits. Pharm Res, 1998 Apr, 15(4), 544 - 9 Drug targeting by polyalkylcyanoacrylate nanoparticles is not efficient against persistent Salmonella; Page-Clisson ME et al.; PURPOSE: We have investigated the efficacy of colistin and ciprofloxacin, free or bound to polyalkylcyanoacrylate nanoparticles, for the targeting and eradication of Salmonella persisting in the organs of the mononuclear phagocyte system . METHODS: A model of persistent S . typhimurium infection was developed in C57BL/6 mice using i.v . inoculation of the plasmid-cured strain C53 . RESULTS: In vivo and ex vivo experiments showed that the persisting bacteria seem to evolve to a nongrowing state during experimental salmonellosis . In vivo treatment with free or nanoparticle-bound colistin did not significantly reduce the number of viable Salmonella C53, either in the liver or the spleen of infected mice . In contrast, in vivo treatment with ciprofloxacin led to a significant decrease of bacterial counts in the liver whatever the stage of infection and the form used . However, none of the treatments were able to sterilize the spleen or the liver . In ex vivo experiments, colistin was only active against bacteria recovered during the early phase of infection, whereas ciprofloxacin exerted its activity at all times postinfection . CONCLUSIONS: We suggest that the micro-environment in which the bacterial cells persist in vivo probably causes dramatic changes in their susceptibility to antimicrobial agents. Res Commun Mol Pathol Pharmacol, 1998 Feb, 99(2), 233 - 9 Effects of hydrazine sulfate on galactosamine-sensitized endotoxic shock in ten-day-old rats; Ravindranath T et al.; Patients who have liver diseases are susceptible to septic shock . Galactosamine induces liver damage and increases endotoxin-sensitivity . Hydrazine stimulates pituitary-adrenal axis and decreases mortality in galactosamine-sensitized endotoxic shock in the adult . However, as pituitary-adrenal function in the newborn is immature, the effects of hydrazine on galactosamine-sensitized endotoxic shock in the newborn remained unclear . In the present study, galactosamine-sensitized endotoxic shock was induced and treated with hydrazine in ten-day-old rats . Galactosamine (600 mg/kg) plus Salmonella enteritidis lipopolysaccharide (LPS; 0.01 mg/kg) induced hypoglycemia, lactacidemia and resulted in high mortality . Hydrazine at the dose of 20, 50 or 80 mg/kg did not alter the hypoglycemia, lactacidemia or morality . Dexamethasone ameliorated the hypoglycemia and lactacidemia (p < 0.05) and decreased the morality (p < 0.05) . The lack of beneficial effects of hydrazine in galactosamine-sensitized endotoxic shock in ten-day-old rats may be related to immature pituitary-adrenal function and suppression of gluconeogenesis by hydrazine. Enferm Infecc Microbiol Clin, 1998 Jan, 16(1), 19 - 24 {Abscess of the psoas muscle: analysis of 11 cases and review of the literature}; Laguna P et al.; BACKGROUND: Abscess of the psoas muscle (AP) is an infrequent disease of difficult diagnosis, developing spontaneously (primary AP) or by extension of a subjacent infection (secondary AP) . In recent years changes have been observed in its etiology, advances in its diagnosis and modifications in the treatment schedules . METHODS: The cases of AP diagnosed from 1983-1996 were retrospectively studied . RESULTS: The cases included 11 AP, 5 (45%) primary and 6 (55%) secondary, of which the source of origin were: spondylitis in four, sacroiliac arthritis in one and intestinal in another . The clinical presentation was characterized by its prolonged course (evolution of symptoms greater than 30 days in 64% of the cases), with the most frequent symptoms being flank/abdominal pain (82%) and hip/inguinal pain (45%), with fever being presented in only 36% . The diagnostic profitability of echography and computerized tomography (CT) were 57% (4/7) and 91% (10/11), respectively . One case was diagnosed with magnetic resonance . The causal microorganisms were: Mycobacterium tuberculosis (36% of the cases), Staphylococcus aureus (18%), polymicrobian flora (18%) and Salmonella enteritidis, Streptococcus intermedius and Escherichia coli in 9% each . Eight cases (73%) underwent percutaneous (5 cases) and surgical (3 cases) drainage, with the evolution being favorable in 10 (91%) and death in one despite adequate medicosurgical treatment . CONCLUSIONS: The clinical presentation of AP is often unspecific, thereby delaying its diagnosis, and thus, CT is the procedure of choice . The tuberculous etiology continues to be frequent in our environment . Ultrasonographic or CT guided percutaneous drainage is a valid therapeutic alternative versus surgery. Biochemistry, 1998 Apr 7, 37(14), 4935 - 45 Mechanistic studies of the biosynthesis of paratose: purification and characterization of CDP-paratose synthase; Hallis TM et al.; The 3,6-dideoxyhexoses can be found in the cell wall lipopolysaccharide of Gram-negative bacteria, where they have been shown to be the dominant antigenic determinants . All naturally occurring 3,6-dideoxyhexoses, with colitose as the only exception, are biosynthesized via a complex pathway that begins with CDP-d-glucose . Included in this pathway is CDP-paratose synthase, an essential enzyme in the formation of the 3,6-dideoxy sugars, CDP-paratose and CDP-tyvelose . Recently, the gene encoding CDP-paratose synthase in Salmonella typhi, rfbS, has been identified and sequenced {Verma, N., and Reeves, P . (1989) J . Bacteriol . 171, 5694-5701} . On the basis of this information, we have amplified the rfbS gene by polymerase chain reaction (PCR) from S . typhi and cloned this gene into a pET-24(+) vector . Expression and purification of CDP-paratose synthase have allowed us to fully characterize the catalytic properties of this enzyme, which is a homodimeric protein with a preference for NADPH over NADH . It catalyzes the stereospecific hydride transfer of the pro-S hydrogen from the C-4' position of the reduced coenzyme to C-4 of the substrate, CDP-3,6-dideoxy-D-glycero-D-glycero-4-hexulose . The overall equilibrium of this catalysis greatly favors the formation of the reduced sugar product and the oxidized coenzyme . Interestingly, this enzyme also exhibits a high affinity for NADPH with a much smaller dissociation constant (Kia) of 0.005 +/- 0.002 microM compared to the Km of 26 +/- 8 microM for NADPH . While this unusual property complicated the interpretation of the kinetic data, the kinetic mechanism of CDP-paratose synthase as explored by the combination of bisubstrate kinetic analysis, product inhibition studies, and dead-end competitive inhibition studies is most consistent with a Theorell-Chance mechanism . The present study on CDP-paratose synthase, a likely new member of the short-chain dehydrogenase family, represents the first detailed characterization of this type of ketohexose reductase, many of which may share similar properties with CDP-paratose synthase. J Biol Chem, 1998 Apr 10, 273(15), 8849 - 59 The assembly system for the lipopolysaccharide R2 core-type of Escherichia coli is a hybrid of those found in Escherichia coli K-12 and Salmonella enterica . Structure and function of the R2 WaaK and WaaL homologs; Heinrichs DE et al.; In Escherichia coli F632, the 14-kilobase pair chromosomal region located between waaC (formerly rfaC) and waaA (kdtA) contains genes encoding enzymes required for the synthesis of the type R2 core oligosaccharide portion of lipopolysaccharide . Ten of the 13 open reading frames encode predicted products sharing greater than 90% total similarity with homologs in E . coli K-12 . However, the products of waaK (rfaK) and waaL (rfaL) each resemble homologs in Salmonella enterica serovar Typhimurium but share little similarity with E . coli K-12 . The F632 WaaK and WaaL proteins therefore define differences between the type R2 and K-12 outer core oligosaccharides of E . coli lipopolysaccharides . Based on the chemical structure of the core oligosaccharide of an E . coli F632 waaK::aacC1 mutant and in vitro glycosyltransferase analyses, waaK encodes UDP-N-acetylglucosamine:(glucose) lipopolysaccharide alpha1, 2-N-acetylglucosaminyltransferase . The WaaK enzyme adds a terminal GlcNAc side branch substituent that is crucial for the recognition of core oligosaccharide acceptor by the O-polysaccharide ligase, WaaL . Results of complementation analyses of E . coli K-12 and F632 waaL mutants suggest that structural differences between the WaaL proteins play a role in recognition of, and interaction with, terminal lipopolysaccharide core moieties. J Biol Chem, 1998 Apr 10, 273(15), 8680 - 90 Binding of bacterial peptidoglycan to CD14; Dziarski R et al.; The hypothesis that soluble peptidoglycan (sPGN, a macrophage-activator from Gram-positive bacteria) binds to CD14 (a lipopolysaccharide (LPS) receptor) was tested . sPGN specifically bound to CD14 in the following three assays: binding of soluble 32P-CD14 (sCD14) to agarose-immobilized sPGN, enzyme-linked immunosorbent assay, and photoaffinity cross-linking . sCD14 also specifically bound to agarose-immobilized muramyl dipeptide or GlcNAc-muramyl dipeptide but not to PGN pentapeptide . Binding of sCD14 to both sPGN and ReLPS (where ReLPS is LPS from Salmonella minnesota Re 595) was competitively inhibited by unlabeled sCD14, 1-152 N-terminal fragment of sCD14, sPGN, smooth LPS, ReLPS, lipid A, and lipoteichoic acid but not by dextran, dextran sulfate, heparin, ribitol teichoic acid, or soluble low molecular weight PGN fragments . Binding of sCD14 to sPGN was slower than to ReLPS but of higher affinity (KD = 25 nM versus 41 nM) . LPS-binding protein (LBP) increased the binding of sCD14 to sPGN by adding another lower affinity KD and another higher Bmax, but for ReLPS, LBP increased the affinity of binding by yielding two KD with significantly higher affinity (7.1 and 27 nM) . LBP also enhanced inhibition of sCD14 binding by LPS, ReLPS, and lipid A . Binding of sCD14 to both sPGN and ReLPS was inhibited by anti-CD14 MEM-18 mAb, but other anti-CD14 mAbs showed differential inhibition, suggesting conformational binding sites on CD14 for sPGN and LPS, that are partially identical and partially different. Mutat Res, 1998 Jan 30, 412(2), 131 - 8 Genotoxicity testing of methyl tertiary-butyl ether (MTBE) in the Salmonella microsuspension assay and mouse bone marrow micronucleus test; Kado NY et al.; Methyl tertiary-butyl ether (MTBE) is an oxygenated fuel additive that is present in gasoline at levels up to 15% by volume . Since the 1990 Clean Air Act amendments require the use of oxygenated gasoline in 39 areas of the USA, the use of MTBE is projected to continue to dramatically increase . As the use of MTBE increase, the potential for environmental release of MTBE from gasoline stations and automobiles will also increase . Despite its growing use as a fuel additive and its potential for increased exposure to the public, few genotoxicity data on MTBE have been published in the peer-review literature . In the present study, we tested the potential genotoxicity of MTBE in two short-term test systems, an in vitro Salmonella microsuspension assay and an in vivo mouse bone marrow micronucleus test . For the microsuspension assay, MTBE was tested at 7 dose levels of 30 to 7400 micrograms/tube in tester strain TA98, TA100, TA104, and TA1535, with and without the addition of metabolic enzymes (S9) at 4 concentration (0, 300, 600, and 1200 micrograms S9/ml final concentration) . A closed system was used to minimize loss of MTBE . The response was not significant . However, a high degree of toxicity was observed at the highest doses in all tester strains . MTBE was also tested for clastogenicity i the mouse bone marrow micronucleus test using both male and female Swiss-Webster mice . Mice were administered single intraperitoneal injections of MTBE in olive oil at 5 doses ranging from 0.25 to 1.75 g/kg . There were no significant increases in micronucleus formation at any dose of MTBE when compared with the negative control animals receiving only olive oil . MTBE was not positive when tested for point mutations and clastogenicity, using respectively, a Salmonella microsuspension assay and the mouse bone marrow micronucleus test. Folia Med (Plovdiv), 1997, 39(4), 17 - 23 A study on some immunological parameters in infants with salmonellosis; Stoicheva M et al.; The phagocytic activity of polymorphonuclears from peripheral blood (PMN) and the qualitative characteristic of lymphocyte populations and circulating immune complexes (CIC) were studied dynamically in 35 infants with salmonellosis . The phagocytic activity of PMNs was evaluated by phagocytic index, phagocytic number, the absolute phagocytic index and the nitroblue tetrazolium test . Lymphocyte populations were determined by immunofluoroscent assay with monoclonal antibodies, and CIC by precipitation with polyethylene glycol . Decreased level of the PMNs phagocytic activity was found in the acute phase of salmonellosis . Both B- and T-lymphopenia with subset dysbalance associated with greater decrease of T4 lymphocytes were identified . During the convalescent period the immunological parameters of the bacteriologically healthy infants were close to normal whereas the Salmonella bacteria carriers demonstrated deviations which persisted in the acute phase of the disease . The immunological parameters studied can be used as additional diagnostic and prognostic criteria in infants with salmonellosis. Prog Clin Biol Res, 1998, 397, 217 - 26 Endotoxin tolerance alters macrophage membrane regulatory G proteins; Makhlouf M et al.; Administration of sublethal doses of endotoxin (LPS) or tumor necrosis factor-alpha (TNF alpha) renders rats tolerant to supralethal doses of LPS . Peritoneal macrophages from tolerant rats are refractory to LPS induced arachidonic acid (AA) metabolism and cytokine production in vivo, and exhibit reduced membrane GTPase activity and GTP gamma S binding . Since LPS stimulated AA metabolism is mediated by Gi alpha proteins, we sought to determine whether Gi alpha and/or other G proteins are reduced in LPS tolerance . Rats were rendered tolerant by two daily sublethal doses of Salmonella enteritidis LPS, 100 micrograms/kg and 500 micrograms/kg administered intraperitoneally . Animals were allowed to rest for 72 hours . Alternatively, tolerance to LPS was induced by sublethal administration of human recombinant TNF alpha (10 micrograms/kg) intraperitoneally 24 hrs before the experiments . Macrophage membrane G protein content was determined by immunoblot analysis with specific antisera to Gi1,2 alpha, Gi3 alpha, Gs alpha and the G protein beta subunits (G beta) . Membrane G proteins were differentially decreased in tolerant macrophages . In macrophages from rats rendered tolerant by sublethal doses of LPS, Gi3 alpha was reduced the most to 48 +/- 8% of control (n = 3, P < 0.05) and this reduction was significant compared to those of other G proteins . Gi1,2 alpha and G beta were reduced to 73 +/- 5% (n = 3, P < 0.05) and 65 +/- 4% (n = 3, P < 0.05) of control respectively . Gs alpha(L) and Gs alpha(H) were also reduced to 61 +/- 5% (n = 3, P < 0.05) and 68 +/- 3% (n = 3, P < 0.05) of control, respectively . In contrast, only Gi3 alpha was reduced in macrophage membranes from rats pretreated with TNF alpha . Gi3 alpha was reduced to 57 +/- 11% of control (n = 4, P < 0.05) whereas Gi1,2 alpha and G beta were not significantly affected . These results demonstrate selective changes in tolerant macrophage membrane G proteins and suggest a potential role for Gi3 alpha in mediating LPS tolerance . The molecular mechanisms underlying these changes and their significance in LPS tolerance merit further investigation. Infect Immun, 1998 May, 66(5), 2310 - 8 Differential early interactions between Salmonella enterica serovar Typhi and two other pathogenic Salmonella serovars with intestinal epithelial cells; Weinstein DL et al.; Salmonella enterica serovar Typhi (hereafter referred to as S . typhi) is a host-restricted pathogen that adheres to and invades the distal ileum and subsequently disseminates to cause typhoid fever in humans . However, S . typhi appears to be avirulent in small animals . In contrast, other pathogenic salmonellae, such as S . enterica serovars Typhimurium and Dublin (S . typhimurium and S . dublin, respectively), typically cause localized gastroenteritis in humans but have been used as models for typhoid fever because these organisms cause a disease in susceptible rodents that resembles human typhoid . In vivo, S . typhi has been demonstrated to attach to and invade murine M cells but is rapidly cleared from the Peyer's patches without destruction of the M cells . In contrast, invasion of M cells by S . typhimurium is accompanied by destruction of these M cells and subsequently sloughing of the epithelium . These data have furthered our view that the early steps in the pathogenesis of typhoidal and nontyphoidal Salmonella serovars are distinct . To extend this concept, we have utilized an in vitro model to evaluate three parameters of initial host-pathogen interactions: adherence of three Salmonella serovars to human and murine small intestinal epithelial cell (IEC) lines, the capacity of these salmonellae to invade IECs, and the ability of the bacteria to induce interleukin-6 (IL-6) in these cell lines as a measure of host cell activation and the host acute-phase response . The results demonstrate that S . typhi adheres to and invades human small IECs better than either S . typhimurium or S . dublin . Interestingly, invA and invE null mutants of S . typhi are able neither to adhere to nor to invade IECs, unlike S . typhimurium invA and invE mutants, which adhere to but cannot invade IECs . S . typhi also induces significantly greater quantities of IL-6 in human small IEC lines than either of the other two Salmonella serovars . These findings suggest that differential host cytokine responses to bacterial pathogens may play an important role in the pathological sequelae that follow infection . Importantly, S . typhimurium did not induce IL-6 in murine IECs . Since S . typhimurium infection in mice is often used as a model of typhoid fever, these findings suggest that, at least in this case, the mouse model does not reflect the human disease . Taken together, our studies indicate that (i) marked differences occur in the initial steps of S . typhi, S . typhimurium, and S . dublin pathogenesis, and (ii) conclusions about S . typhi pathogenesis that have been drawn from the mouse model of typhoid fever should be interpreted conservatively. Infect Immun, 1998 May, 66(5), 2060 - 4 Delivery of the p67 sporozoite antigen of Theileria parva by using recombinant Salmonella dublin: secretion of the product enhances specific antibody responses in cattle; Gentschev I et al.; The p67 sporozoite antigen of Theileria parva has been fused to the C-terminal secretion signal of Escherichia coli hemolysin and expressed in secreted form by attenuated Salmonella dublin aroA strain SL5631 . The recombinant p67 antigen was detected in the supernatant of transformed bacterial cultures . Immunization trials in cattle revealed that SL5631 secreting the antigen provoked a 10-fold-higher antibody response to p67 than recombinant SL5631 expressing but not secreting p67 . Immunized calves were challenged with a 80% lethal dose of T . parva sporozoites and monitored for the development of infection . Two of three calves immunized intramuscularly with the p67-secreting SL5631 strain were found to be protected, whereas only one of three animals immunized with the nonsecreting p67-expressing SL5631 strain was protected . This is the first demonstration that complete eukaryotic antigens fused to the C-terminal portion of E . coli hemolysin can be exported from attenuated Salmonella strains and that such exported antigens can protect cattle against subsequent parasite challenge. Infect Immun, 1998 May, 66(5), 1999 - 2006 Identification of epitope and surface-exposed domains of Shigella flexneri invasion plasmid antigen D (IpaD); Turbyfill KR et al.; Transport and surface expression of the invasion plasmid antigens (Ipa proteins) is an essential trait in the pathogenicity of Shigella spp . In addition to the type III protein secretion system encoded by the mxi/spa loci on the large virulence plasmid, transport of IpaB and IpaC into the surrounding medium is modulated by IpaD . To characterize the structural topography of IpaD, the Geysen epitope-mapping system was used to identify epitopes recognized by surface-reactive monoclonal and polyclonal antibodies produced against purified recombinant IpaD or synthetic IpaD peptides . Surface-exposed epitopes of IpaD were confined to the first 180 amino acid residues, whereas epitopes in the carboxyl-terminal half were not exposed on the Shigella surface . By using convalescent-phase sera from 10 Shigella flexneri-infected monkeys, numerous epitopes were mapped within a surface-exposed region of IpaD between amino acid residues 14 and 77 . Epitopes were also identified in the carboxyl-terminal half of IpaD with a few convalescent-phase sera . Comparison of IpaD epitope sequences with Salmonella SipD sequences indicated that very similar epitopes may exist in the carboxyl-terminal region of each protein whereas the IpaD epitopes in the surface-exposed amino-terminal region were unique for the Shigella protein . Although the IpaD and SipD homologs may play similar roles in transport, the dominant serum antibody response to IpaD is against the unique region of this protein exposed on the surface of the pathogen. N Engl J Med, 1998 May 7, 338(19), 1333 - 8 Emergence of multidrug-resistant Salmonella enterica serotype typhimurium DT104 infections in the United States; Glynn MK et al.; BACKGROUND: Strains of salmonella that are resistant to antimicrobial agents have become a worldwide health problem . A distinct strain of Salmonella enterica serotype typhimurium, known as definitive type 104 (DT104), is resistant to ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline and has become a major cause of illness in humans and animals in Europe, especially the United Kingdom . METHODS: To characterize typhimurium DT104 infections in the United States, we analyzed data collected by local and state health departments and public health laboratories between 1979 and 1996 in national surveys of the antimicrobial-drug resistance of salmonella . Selected typhimurium isolates with the five-drug pattern of resistance were phage typed . RESULTS: The prevalence of typhimurium isolates with the five-drug pattern of resistance increased from 0.6 percent in 1979-1980 to 34 percent in 1996 . In 1994-1995, such isolates were identified in samples from 36 of the 46 surveillance sites (78 percent) . Thirty-nine of 43 typhimurium isolates with the five-drug pattern of resistance identified in 1994-1995 and 1996 were phage type DT104 or a closely related phage type . CONCLUSIONS: Multidrug-resistant typhimurium DT104 has become a widespread pathogen in the United States . More prudent use of antimicrobial agents in farm animals and more effective disease prevention on farms are necessary to reduce the dissemination of multidrug-resistant typhimurium DT104 and to slow the emergence of resistance to additional agents in this and other strains of salmonella. Lett Appl Microbiol, 1998 Feb, 26(2), 131 - 5 High-resolution genotyping of Salmonella strains by AFLP-fingerprinting; Aarts HJ et al.; High resolution AFLP fingerprinting, in which subsets of genomic restriction fragments are amplified by means of PCR, was used for the identification of different . Salmonella serotypes to investigate whether this technique is applicable in epidemiological studies . Seventy-eight different Salmonella strains comprising 62 serotypes were genetically identified by AFLP . Primer combination M00 (MseI primer without additional 3' nucleotides) and E11 (EcoRI primer with two additional 3' nucleotides) resulted in reproducible profiles containing approximately 50 bands . All serotypes were characterized by a unique profile . In addition, AFLP fingerprinting enabled phage type identification . Different strains previously identified as identical, using typing methods with lower resolution, could be distinguished, showing that AFLP fingerprinting is well suited for bacterial epidemiology and identification. Eur J Clin Invest, 1998 Mar, 28(3), 205 - 13 Different efficacy of soluble CD14 treatment in high- and low-dose LPS models; Stelter F et al.; BACKGROUND: About 50% of septic shock cases are attributed to Gram-negative bacteria or their cell wall compound lipopolysaccharide (LPS, endotoxin) . An attractive therapeutic strategy could target the binding of LPS to its cellular receptors . In vitro the soluble form of the endotoxin receptor CD14 (sCD14) competitively prevents binding of LPS to membrane-bound CD14 and inhibits LPS-stimulated macrophage responses . METHODS: We tested the in vivo endotoxin-neutralizing capacity of human recombinant sCD14 using a mouse model of shock induced by 8 micrograms g-1 of LPS from Salmonella abortus equi . RESULTS: In this model, treatment with sCD14 reduced mortality if administered before or simultaneously with LPS . However, application of sCD14 had no effect on the secretion of early proinflammatory cytokines and did not protect the animals against the development of apparent shock symptoms and liver injury . sCD14 also failed to prevent LPS-inducible (7.5 ng g-1) liver injury in galactosamine-sensitized mice . CONCLUSION: In line with these findings, sCD14 did not block LPS-induced activation of Kupffer cells in vitro, which might explain why the compound only partially protected in vivo. Rev Sci Tech, 1997 Dec, 16(3), 891 - 7 Decontamination of chicken carcasses artificially contaminated with Salmonella; Nassar TJ et al.; A study was conducted to evaluate the efficacy of three chemical disinfectants and of ionising radiation in reducing the level of contamination in chicken carcasses which had been artificially contaminated with Salmonella Virchow . Chicken carcasses were obtained from a local abattoir . Five carcasses and one control carcass were used to test each concentration of disinfectant and the radiation . The amount of contaminant employed was 0.5 ml of 10(4) colony-forming units per ml of S . Virchow spread over the thigh, breast and wing areas . All treatments were conducted in duplicate . The three disinfectants used were as follows: calcium hypochlorite, at concentrations of 20 ppm, 50 ppm, 100 ppm and 200 ppm of available chlorine . Lactic acid at concentrations of 0.5%, 0.75% and 1% . Hydrogen peroxide compound at concentrations of 1%, 2% and 3% . Five inoculated carcasses were immersed at a time in one disinfectant concentration for 15 min, while the control carcasses were simultaneously immersed in water free from disinfectants . Five carcasses, each in a plastic bag, were subjected to varying ascending doses (from 2 to 7 k gray {kGy}) of ionising radiation from radioactive isotopes of cobalt 60 . A bacteriological examination of each carcass was conducted after the treatment to determine the presence or absence of S . Virchow . The number of carcasses which gave positive results showing the presence of Salmonella decreased after chemical treatment, but the organism was not completely eliminated . However, in those carcasses subjected to 7 kGy of radiation, Salmonella was eliminated and no changes in the appearance, colour or smell of the carcasses were observed. Rev Sci Tech, 1997 Dec, 16(3), 885 - 90 The Swiss control programme for Salmonella enteritidis in laying hens: experiences and problems; Hoop RK; The Swiss control programme for Salmonella Enteritidis began at the end of 1993 . All efforts are focused on the elimination of infected parent and layer flocks and on the production of S . Enteritidis-free eggs . The new Zoonosis Order and more stringent import regulations help to identify S . Enteritidis-positive parent layer and layer flocks . Other measures, such as additional voluntary monitoring of parent layer flocks, hatcheries and layer flocks, increased hygiene on poultry farms and the use of heat-treated feed, serve to prevent the spread of S . Enteritidis . An important point of concern is the elimination of S . Enteritidis from contaminated poultry farms, particularly from free-range farms . In the last two years, the number of reported infections of S . Enteritidis in humans has almost fallen to the level of 1988 (the year before the onset of S . Enteritidis infection in laying hens in Switzerland). Vaccine, 1998 Apr, 16(7), 732 - 40 LT(R192G), a non-toxic mutant of the heat-labile enterotoxin of Escherichia coli, elicits enhanced humoral and cellular immune responses associated with protection against lethal oral challenge with Salmonella spp; Chong C et al.; In the current study we examined the ability of a novel mucosal adjuvant, LT(R192G), to enhance the humoral and cellular immune responses against killed Salmonella spp . and to affect protection against lethal oral challenge with wild-type organisms . Mice orally immunized with killed S . dublin in conjunction with LT(R192G) were protected against lethal oral challenge and had higher IFN-gamma, IL-2 and IgG responses than did mice orally immunized with killed S . dublin alone which were not protected . This study demonstrates that the function of LT(R192G) in protection against typhoid-like disease is to upregulate/enhance the Th1 arm of the immune response against killed organisms . When used as a mucosal adjuvant, LT(R192G) enables the use of killed bacteria or viruses as vaccines by enhancing the overall humoral and cellular host immune response to these organisms, especially the Th1 arm of the immune response . These findings have significant implications for vaccine development and further support the potential of LT(R192G) to function as a safe, effective adjuvant for mucosally administered vaccines. FEMS Microbiol Lett, 1998 Apr 1, 161(1), 201 - 8 Salmonella typhi rpoS mutant is less cytotoxic than the parent strain but survives inside resting THP-1 macrophages; Khan AQ et al.; Transcription of the stationary-phase sigma factor RpoS of Salmonella typhi increased in the macrophage . A single rpoS mutant of S . typhi was constructed to analyze the role of RpoS in intracellular multiplication of the bacterium and host cell killing . This mutant was sensitive to starvation, low pH and hydrogen peroxide; however, it could still multiply inside resting macrophages and was less cytotoxic than the wild-type strain . Therefore, S . typhi might produce RpoS-dependent factors which could contribute to host cell death. FEMS Microbiol Lett, 1998 Apr 1, 161(1), 129 - 33 General transducing phages like Salmonella phage P22 isolated using a smooth strain of Escherichia coli as host; Dhillon TS et al.; A smooth colony strain, resistant to phages lambda and P22, was isolated from sewage and identified as Escherichia coli (strain H) . Four temperate phages plaquing on strain H were isolated from sewage . The archetype, HK620, does not plaque on strains C and K12 of E . coli nor on the LT2 strain of Salmonella enterica . Bacterial mutants resistant to a clear plaque mutant of HK620 produce rough colonies . Some are also galactose-negative, a few are histidine auxotrophs, and most show sensitivity to lambda . HK620 can transduce a wide variety of auxotrophic mutants of E . coli H to prototrophy . It can recombine with lambda but its virions resemble those of P22. FEMS Microbiol Lett, 1998 Apr 1, 161(1), 75 - 82 Vi-deficient and nonfimbriated mutants of Salmonella typhi agglutinate human blood type antigens and are hyperinvasive; Miyake M et al.; We generated nonfimbriated mutants from both Vi-positive and -negative Salmonella typhi to analyze the role of type 1 fimbriae and Vi-antigen in bacterial invasion . A Vi-defective mutant of S . typhi GIFU 10007-3 was more invasive than the wild-type strain GIFU 10007 . The wild-type strain expressing Vi-antigen did not agglutinate both Saccharomyces cerevisiae and human erythrocytes but Vi-defective mutants were able to agglutinate S . cerevisiae and human erythrocytes . Nonfimbriated mutants from Vi-negative GIFU 10007-3 lost the ability to adhere to S . cerevisiae but still could agglutinate human erythrocytes . The Vi-negative mutant increased secreted proteins and became 5-fold more invasive than the wild-type strain . Nonfimbriated Vi mutants became 50-120-fold more invasive than the wild-type GIFU 10007 . To determine why nonfimbriated Vi mutants still agglutinate human red blood cells, we searched bacterial proteins that could bind human blood-type antigens . We finally identified a candidate 37 kDa outer membrane protein that recognized fucosyl-galactose, a structure common to blood type A, B and H antigens. J Hosp Infect, 1998 Mar, 38(3), 207 - 16 Random amplification of polymorphic DNA (RAPD), pulsed-field gel electrophoresis (PFGE) and phage-typing in the analysis of a hospital outbreak of Salmonella enteritidis; Skibsted U et al.; Isolates of Salmonella Enteritidis from 81 patients from Herlev Hospital or from Copenhagen County were analysed by random amplification of polymorphic DNA (RAPD), pulsed-field gel electrophoresis (PFGE) and phage-typing . Fourteen polymorphic markers from five decamer primers unambiguously placed all isolates into six RAPD groups: 65 isolates of phagetype 6 (PFGE type I) were resolved into three RAPD groups constituting 86, 12, and 2%, respectively . A fourth RAPD group of 10 isolates was coincident with phage type 8 (PFGE type II) and two isolates, one phage-type 1, the other phage-type 4 (both PFGE type I) formed the fifth group . The sixth group of four isolates was not phage typeable and was PFGE type III . Forty outbreak-related isolates of phage-type 6 were resolved into three strains . No diversity of phage-type 6 was found among isolates unrelated to the outbreak . It is concluded that RAPD is useful as a tool in investigations of microbial outbreaks in its own right, or to supplement phage-typing and PFGE of Salmonella Enteritidis. Antimicrob Agents Chemother, 1998 Apr, 42(4), 739 - 43 Antibiotic-induced lipopolysaccharide (LPS) release from Salmonella typhi: delay between killing by ceftazidime and imipenem and release of LPS; van Langevelde P et al.; It has been suggested that the antibiotic-induced release of lipopolysaccharide (LPS) is an important cause of the development of septic shock in patients treated for severe infections caused by gram-negative bacteria . Beta-lactam antibiotics change the integrity of the bacterial cell envelope by binding to penicillin-binding proteins (PBP) in the membrane and thus may affect the amount of LPS that is released and the kinetics of that release . In this respect, ceftazidime at intermediate concentrations binds with a high affinity to PBP 3 and PBP 1a and thus can induce filament formation in addition to killing, whereas imipenem preferentially binds to PBP 2 and PBP 1b, leading to spheroplast formation and rapid cell lysis . We investigated the effects of these antibiotics on the killing and the release of the radioactively labelled LPS of Salmonella typhi Ty 21A . A mathematical model was developed to calculate the delay between bacterial killing and LPS release, designated the lag time . At antibiotic concentrations inducing equal killing, the amount of LPS released was the same for both antibiotics . Only after 6 h of incubation at antibiotic concentrations above 0.5 microg/ml, the amount of 3H-LPS released was slightly higher (approximately 1.2-fold) in incubations with ceftazidime than in those with imipenem, and the maximum releases of the total label were 33.2% +/- 0.89% and 27.1% +/- 0.45%, respectively . Despite the clear concentration-dependent effect on the bacterial killing and subsequent LPS release, the lag time was independent of the antibiotic concentration . For ceftazidime as well as imipenem the lag time amounted to approximately 60 min . In conclusion, our findings imply that the mechanism of antibiotic-induced LPS release is independent of the PBP affinities for these beta-lactam antibiotics . Furthermore, once the organism is killed by either imipenem or ceftazidime, the rate of LPS release from S . typhi does not differ according to the antibiotic with which the organism is killed, and there is little difference in the relative amount of LPS released. Jpn Circ J, 1998 Feb, 62(2), 139 - 41 Purulent pericarditis with tamponade caused by Salmonella enteritidis; Kiuchi K et al.; The incidence of purulent pericarditis has declined . However, mortality remains high . We describe a case of purulent pericarditis with tamponade caused by Salmonella enteritidis, and emphasize the importance of early recognition, prompt institution of appropriate antibiotic therapy, and early surgical drainage for survival. Jpn J Thorac Cardiovasc Surg, 1998 Feb, 46(2), 231 - 5 {A case of ruptured descending thoracic aortic aneurysm due to Salmonella infection}; Tabuchi A et al.; A 66-year-old male was admitted to our hospital because of pyrexia, chest pain and hemosptum . Inflammatory findings were made and salmonella enteritidis was detected by bacterial examination of sputum and stool . Enhanced chest CT examination disclosed a descending thoracic aortic aneurysm which had ruptured into the left lower lobe of the lung . Under a diagnosis of ruptured mycotic descending thoracic aortic aneurysm, an emergency operation was performed . A left posterolateral thoracotomy carried out after axillo-bilateral femoral bypass grafting . A pseudoaneurysm of the descending thoracic aorta had ruptured into the left lower lobe of the lung . After resection of the aneurysm, closure of both ends of the intact descending thoracic aorta and a left lower lobectomy were carried out . An ascending aorta-infrarenal abdominal aorta bypass was performed because of insufficient visceral arterial blood flow through the axillo-bilateral femoral bypass . The patient's immediate postoperative recovery was complicated by paraplegia . Chloramphenicol and levofloxacin were administered for three months, after which his recovery followed a good course. East Afr Med J, 1997 Nov, 74(11), 708 - 13 Antibiotic resistance of prevalent Salmonella and Shigella strains in northwest Ethiopia; Aseffa A et al.; Salmonella and Shigella strains were isolated prospectively from in- and outpatient specimens of the Gondar College teaching hospital over a two year period, from June 1994 to May 1996 . Of 7993 miscellaneous specimens cultured, 80 yielded Salmonella and 147 Shigella . Serogroup B dominated among the salmonella, accounting for 61% of isolates, followed by S . typhi (21%) . S . flexneri (58.5%) and S . dysenteriae (36.7%) were the most frequently isolated species among the Shigella . Results of sensitivity testing to five commonly used antibiotics in the area: ampicillin, chloramphenicol, gentamicin, tetracycline and cotrimoxazole, showed multiple drug resistance among the isolates of both salmonella and shigella . Only 4% of shigella were sensitive to all five antibiotics screened for in the study . Overall sensitive of shigella isolates to individual antibiotics was 8.8% to tetracycline, 10% to ampicillin, 28% to co-trimoxazole and 98% to gentamicin . No resistance was observed to nalidixic acid among 108 shigella strains tested for this antibiotic . The continued sensitivity of S . typhi to chloramphenicol, cotrimoxazole, ampicillin and the other commonly used antibiotics is noted . It is recommended that nalidixic acid be introduced into the area under strict regulation for treatment of severe cases of shigella dysentery, an illness which is highly endemic in the region and the cause of occasional epidemics with high mortality. Zentralbl Veterinarmed B, 1998 Mar, 45(2), 95 - 103 A Salmonella monitoring programme in egg production farms in Germany; Geue L et al.; A programme monitoring the prevalence of Salmonella infections in egg production farms with different types of flock management was conducted over a period of 18 months . Three laying hen farms with floor pens and five farms with batteries were examined from September 1992 to March 1994 . A total of 569 samples (293 feed and 276 faeces) were processed in parallel by fivefold fractional enrichment in Rappaport/Vasiliadis medium and in potassium tetrathionate crystal violet broth . By using such elaborate methods, high detection rates of Salmonella were obtained . Two thirds of all isolates were found in the third to fifth selective enrichment procedure . Salmonella (S.) Tennessee was the most common serovar isolated (from 24.5% of the samples) whereas S . Enteritidis was the second most common isolate (23.7%) . Salmonella were isolated from 33.1% of the feed samples (97/293), a result which may stimulate further discussion on the prevention of potential contamination of feed stuff with Salmonella and other pathogens . The number of Salmonella isolations from floor pens was significantly higher than from batteries . As time progressed an increase in the number of Salmonella isolations occurred in samples taken from the floor pens . The development of a less costly routine monitoring programme to detect Salmonella in samples taken from barns with layer flocks is recommended. J Bacteriol, 1998 Apr, 180(8), 2220 - 3 Mosaic structure of the smpB-nrdE intergenic region of Salmonella enterica; Baumler AJ et al.; The Salmonella enterica smpB-nrdE intergenic region contains about 45 kb of DNA that is not present in Escherichia coli . This DNA region was not introduced by a single horizontal transfer event, but was generated by multiple insertions and/or deletions that gave rise to a mosaic structure in this area of the chromosome. Int J Antimicrob Agents, 1997 Jan, 9(3), 195 - 9 Inhibition of Listeria monocytogenes and Salmonella enteriditis by combinations of plant oils and derivatives of benzoic acid: the development of synergistic antimicrobial combinations; Fyfe L et al.; This study describes inhibitory properties of combinations of oil of fennel, oil of anise or oil of basil with either benzoic acid or methyl-paraben against Listeria monocytogenes and Salmonella enteriditis . Micro-organisms were cultured at 37 degrees C in broth and viable counts measured over a 48-h period . S . enteriditis was particularly sensitive to inhibition by a combination of oil of anise, fennel or basil with methyl-paraben where there was < 10 CFU/ml after 1 h . L . monocytogenes was less sensitive to inhibition by each combination however there was a significant reduction in growth of 4-8 log by combinations of all oils and methyl-paraben at 8, 24 and 48 h . Synergistic inhibition by one or more combinations was evident against each micro-organism. Chirurg, 1998 Feb, 69(2), 204 - 6; discussion 207 {Salmonella enteritidis infected false aneurysm of the superficial femoral artery in an HIV seropositive patient}; Grotemeyer D et al.; In the course of an infection with human immunodeficiency virus, a large variety of complications affecting all organ systems can occur . However, complications affecting the vascular system demanding surgical intervention are rare . In the case presented we report a 67-year-old HIV-seropositive patient who underwent surgery for a huge abscess in the thigh . Intraoperatively unexpectedly we found a mycotic aneurysm of the femoral superficial artery and the causactive bacterium proved to be Salmonella enteritidis . Because of the rising number of HIV-infected patients we suspect that the amount of complications involving the vascular system and demanding surgical intervention will also increase . Therefore, when diagnosing and deciding on therapy for patients with AIDS, the physician must be aware that vascular complications due as a result of HIV infection might occur more frequently in the future. Naunyn Schmiedebergs Arch Pharmacol, 1998 Mar, 357(3), 252 - 9 A therapeutic dosage of amlodipine prevents vascular hyporeactivity induced in rats by lipopolysaccharide; Salomone S et al.; The aim of this work was to investigate whether treatment with the 1,4-dihydropyridine Ca2+ antagonist amlodipine could affect the vascular hyporesponsiveness induced by cytokines . Endotoxemia was induced by Salmonella typhosa lipopolysaccharide (LPS) injection (4 mg kg(-1), i.p.) . In endothelium-denuded rings of thoracic aorta from untreated rats, contractile response to noradrenaline was decreased after LPS injection, this effect was partially overcome by the addition of N(omega)-nitro-L-arginine (L-NNA, 100 microM) into the bathing solution . In amlodipine-pretreated rats (15 mg kg(-1) day(-1), orally, for one week), the effect of LPS was lower than in untreated ones and it was completely reversed by L-NNA . The relaxation of the noradrenaline-induced tone evoked by L-arginine (10 microM) in aortae of LPS-injected rats was reduced in amlodipine-pretreated rats . Amlodipine-treatment reduced both the LPS-induced Ca2+-independent NOS activity in homogenates of heart and the expression of iNOS mRNA in aortae of LPS-injected rats . However, the vascular hyporeactivity induced by exposing aortae to interleukin-1beta in vitro was not influenced by amlodipine (10 nM) . Amlodipine (10 microM) also did not affect the production of nitrite in primary aortic smooth muscle cell culture challenged by LPS although nitrite production in macrophage culture challenged with LPS was significantly inhibited . The results show that rat pretreatment with amlodipine prevented the decrease of vascular responsiveness induced by LPS, an effect that may be at least partly related to reduction of in vivo NOS induction . The weak effect of amlodipine on the in vitro NOS induction indicates that the protective action in endotoxemia did not result from a short term interaction with L-type Ca2+ channels in vascular smooth muscle . Alternative mechanisms are discussed. Tohoku J Exp Med, 1997 Dec, 183(4), 273 - 84 Dibutyryl cAMP inhibits endotoxin-induced increases in pulmonary vascular resistance and fluid filtration coefficient in the perfused rat lung; Takeoka M et al.; We investigated the effects of pre-treatment with dibutyryl cAMP (db-cAMP) or cGMP on endotoxin-induced hemodynamic changes and pulmonary vascular permeability in isolated perfused rat lungs . Intraperitoneal injection of Salmonella enteritidis endotoxin (2 mg/kg) caused increases in pulmonary arterial resistance (Ra) after venous reservoir elevation, in pulmonary filtration coefficient (Kf) and in lung wet-to-dry (W/D) weight ratio . Pre-treatment with db-cAMP blocked endotoxin-induced increases in Ra, Kf and W/D weight ratio . Pre-treatment with cGMP attenuated only the increase in Ra caused by endotoxin . Moreover, administration of db-cAMP 2 hours after endotoxin injection attenuated the increase in Ra induced by endotoxin treatment . The increases in Kf and W/D weight ratio caused by endotoxin were not affected by post-treatment with db-cAMP . Since the increases in Ra, Kf and W/D weight ratio caused by endotoxin were blocked by pre-treatment with db-cAMP, agents that increase intracellular cAMP level may be useful to prevent acute pulmonary vascular injury. J AOAC Int, 1998 Mar-Apr, 81(2), 419 - 37 LOCATE enzyme-linked immunosorbent assay for detection of Salmonella in food: collaborative study; Gangar V et al.; A collaborative study was performed in 27 laboratories to validate the enzyme-linked immunosorbent procedure LOCATE for rapid detection of Salmonella in foods . Results were read visually and with a microtiter plate reader . The LOCATE method was compared with the Bacteriological Analytical Manual (BAM)/AOAC INTERNATIONAL culture method for detecting Salmonella in 6 foods: milk chocolate, nonfat dry milk, dried whole egg, soy flour, ground black pepper, and ground raw turkey . Two foods--dried whole egg and black pepper--required repeat rounds because insufficient data sets were produced initially (AOAC INTERNATIONAL stipulates a minimum of 15 sets per food type) . Each laboratory tested one or more of the 6 foods . A total of 1 439 samples were analyzed, and no significant differences (P < 0.05) were observed between LOCATE with either visual or reader detection and BAM/AOAC INTERNATIONAL results . The LOCATE screening method with visual or reader detection is recommended for Official First Action Approval. Mutat Res, 1998 Feb 2, 397(2), 313 - 35 Induction of forward mutations at the thymidine kinase locus of mouse lymphoma cells: evidence for electrophilic and non-electrophilic mechanisms; Henry B et al.; A database of 209 chemicals tested for induction of forward mutations at the heterozygous thymidine kinase (TK +/-) locus in L5178Y mouse lymphoma cells was analyzed for structure-activity relationships using the MultiCASE expert system . Consistent with evidence of several contributing biological mechanisms, these studies suggest that such mutations may occur by more than one mechanism . As might be expected, there was evidence for a component involving direct electrophilic attack on the cellular DNA, in a manner previously established as causative in the induction of mutations in Salmonella . In addition, however, there was also strong evidence for another mechanism or mechanisms involving chromosome missegregation, cellular toxicity or an alternate site of action, such as the microtubules. Nucleic Acids Res, 1998 Mar 15, 26(6), 1373 - 81 DNA binding and oligomerization of NtrC studied by fluorescence anisotropy and fluorescence correlation spectroscopy; Sevenich FW et al.; Fluorescence anisotropy and fluorescence correlation spectroscopy measurements of rhodamine-labeled DNA oligonucleotide duplexes have been used to determine equilibrium binding constants for DNA binding of the prokaryotic transcription activator protein NtrC . Measurements were made with wild-type NtrC from Escherichia coli and the constitutively active mutant NtrCS160Ffrom Salmonella using DNA duplexes with one or two binding sites . The following results were obtained: (i) the dissociation constant K d for binding of one NtrC dimer to a single binding site was the same for the wild-type and mutant proteins within the error of measurement . (ii) The value of K d decreased from 1.4 +/- 0.7 x 10(-11) M at 15 mM K acetate to 5.8 +/- 2.6 x 10(-9) M at 600 mM K acetate . From the salt dependence of the dissociation constant we calculated that two ion pairs form upon binding of one dimeric protein to the DNA . (iii) Binding of two NtrC dimers to the DNA duplex with two binding sites occured with essentially no cooperativity . Titration curves of NtrCS160Fbinding to the same duplex demonstrated that more than two protein dimers of the mutant protein could bind to the DNA. Schweiz Rundsch Med Prax, 1998 Feb 25, 87(9), 318 - 21 {Febrile state, bloody diarrhea and megacolon}; Hellermann J et al.; We report about a forty year old female patient with severe bloody diarrhoea and fever over a period of 14 days due to an infection with Salmonella enteritidis . X-ray of the abdomen showed a toxic megacolon . With the diagnosis of an infectious colitis we started therapy with ciprofloxacin i/v . The toxic megacolon progressed despite intensive care and parenteral nutrition . Additionally the patient received metronidazole i/v and in combination with a roll technique in bed in the knee-elbow-position the leucocytosis and the megacolon decreased . A toxic megacolon is in about 3% associated with an infection with Salmonella enteritidis . It is essentially diagnosed by X-ray . Patients should receive intensive care, and because of the high mortality rate an interdisciplinary management is required . The article discusses the major differential diagnosis of the toxic megacolon, as well as the pathogenesis and therapy of Salmonella ent, infection . In case of an infection with Salmonella ent . physicians should acknowledge the possibility of development of a toxic megacolon. Environ Mol Mutagen, 1998, 31(2), 169 - 75 Comparative studies of the mutagenicity of environmental tobacco smoke from cigarettes that burn or primarily heat tobacco; Bombick BR et al.; The mutagenicity of particulate matter concentrated from environmental tobacco smoke (ETS) from a prototype cigarette that primarily heats tobacco was compared to that of four popular commercially available cigarettes that burn tobacco . ETS was generated by six individuals simultaneously smoking 1 cigarette each in a 20-min time period in a 45 m3 environmental chamber operated in the static mode (without ventilation) . Respirable suspended particles (RSP) were collected on polytetrafluoroethylene (PTFE) filters at a flow rate of 3 LPM for 120 min . Less ETS-RSP (86-90%) was emitted by the prototype tobacco-heating cigarette than by the tobacco-burning cigarettes . RSP was extracted from the filters by sequential sonication in acetone and dichloromethane . The acetone extract was dried under nitrogen and the dichloromethane filtrate was added and then dried to obtain ETS-RSP for testing . Mutagenicity was assessed in the microsuspension modification of the Ames Salmonella/microsome assay with strains TA98 and YG1024 in the presence of 5% S9 metabolic activation . The results show that the mutagenic activity of RSP from the prototype cigarette was reduced by 75-83% on a per-mg basis when compared to the commercially available cigarettes and was reduced by 96-98% when calculated as revertants/m3 air under identical smoking conditions. J Ultrasound Med, 1998 Apr, 17(4), 231 - 7 Sonographic analysis of gallbladder findings in Salmonella enteric fever; Shetty PB et al.; The purpose of this study was to analyze gallbladder sonographic findings associated with Salmonella typhi enteric fever . Sixty-two patients with culture positive Salmonella enteric fever were analyzed with serial sonography . The following gallbladder sonographic findings were noted: globular gallbladder distention (33 of 62 patients, 530%), positive sonographic Murphy sign (25 patients, 40%), pericholecystic edema or fluid (25 patients, 40%), gallbladder wall thickening > 4 mm (21 patients, 34%), low-level nonshadowing intraluminal echoes or sludge (nine patients, 15%), intramural linear sonolucency or striation (eight patients, 13%), and mucosal irregularity or sloughed membrane (four patients, 6%) . Using the sonographic findings a gallbladder score was devised to assess the severity of gallbladder changes, and the score was correlated with the following clinical parameters--duration of fever, multidrug resistance, and clinical outcome . An abnormal gallbladder score was noted in 37 patients (60%), and multidrug resistance was noted in 35 of these patients (95%) . The gallbladder scores showed a strong positive correlation with the duration of fever and the frequency of multidrug resistance . All 62 patients were treated with intensive antibiotic therapy without any deaths. Arch Pediatr, 1997 Dec, 4(12), 1175 - 81 {Salmonella meningitis in children in Libreville . Retrospective study of 9 cases}; Koko J et al.; BACKGROUND: Salmonella meningitis is a rare entity, even in tropical area where salmonellosis is common . Its prognosis is poor and the choice of adequate antibiotic therapy is difficult . PATIENTS AND METHODS: The files of nine children (three boys, six girls) admitted to the pediatric unit of the Owendo Pediatric Hospital in Libreville for salmonella meningitis between January 1, 1989, and December 31, 1993 were retrospectively studied . Diagnosis was established by a positive culture of cerebrospinal fluid . RESULTS: Salmonella was the third cause (8.65%) of purulent meningitis observed during this period . Eight children were less than 1-year old, seven were from low socioeconomic standard families . The main clinical manifestations were fever (seven cases), pallor (six cases), diarrhea (four cases), nuchal rigidity (four cases), convulsions (three cases) and bulging fontanel (three cases) . Five children (55.5%) were severely anemic (hemoglobin < 5 g/dL) but none had abnormal hemoglobin . Serotyping could not be performed in any case . Salmonella isolates were resistant to chloramphenicol in six cases and to ampicillin in five . Cefotaxime (200 mg/kg/24 h intravenously in three divided doses) was given to seven patients . The duration of therapy was at least 3 weeks in four patients . There were five deaths at ages ranging from 1 to 12 months, ie, a case fatality rate of 55.5% . Three patients (33.3%) recovered with neurological sequels . CONCLUSION: The prognosis of salmonella meningitis is poor, even in the case of prompt diagnosis and adequate therapy . Preventive measures only can decrease the risk of illness in children. Ir J Med Sci, 1998 Jan-Mar, 167(1), 19 - 21 Bacterial toxin-induced pulmonary epithelial cytotoxicity and the protective effect of dibutyryl-cAMP; Bourke W et al.; Bacterial infection is the most common cause of the adult respiratory distress syndrome which, in turn is associated with endothelial capillary permeability and alveolar oedema . Previously, we have demonstrated the direct cytotoxicity of the bacterial toxins Pseudomonas aeruginosa exotoxin A (Exo A) and Salmonella enteritidis lipopolysaccharide (LPS) on pulmonary endothelial cells . The purpose of this study was to investigate the effect of Exo A and LPS on pulmonary epithelial cells in vitro . We also tested the protective effect of dibutyryl cyclic adenosine monophosphate (db-cAMP) on Exo A-induced cytotoxicity . In cultured rat alveolar epithelial cells (RAEC) Exo A caused cytotoxicity as measured by 51Cr release from these cells . LPS did not injure RAEC's . Pretreatment of RAEC with db-cAMP (1 mM) attenuated Exo A induced cytotoxicity . We conclude that (1) Exo A directly injures epithelial lung cells and may contribute to lung injury in cases of bacterial infection; (2) db-cAMP protects alveolar epithelial cells against Exo A-induced cytotoxicity and (3) alveolar epithelial cells in this model are resistant to LPS induced injury. Mutat Res, 1998 Jan 30, 412(2), 167 - 75 Studies on the effect of the solvents dimethylsulfoxide and ethyleneglycoldimethylether on the mutagenicity of four types of diisocyanates in the Salmonella/microsome test; Herbold B et al.; The mutagenicity of isomers and homologs of diphenylmethanediisocyanate (4,4'-diisocyanatodiphenylmethane, 2,4'-diisocyanatodiphenylmethane, a mixture of monomeric MDI isomers, and polymeric MDI), containing 55-100% of monomeric MDI, was determined in the Salmonella/microsome test using dimethylsulfoxide (DMSO) and ethyleneglycoldimethylether (EGDE) as solvents . Positive results were obtained for DMSO solutions of all four diisocyanates in the presence of S9 mix containing 30% S9 fraction . Uniformly negative results were found when the diisocyanates were dissolved in EDGE . These results correspond to those of analytical investigations . A small amount of diaminodiphenylmethane (MDA) is one of the reaction products formed when MDI is dissolved in commercial DMSO . No MDA could be detected in solutions of MDI in EGDE . It is therefore concluded that the positive results obtained with diisocyanates in DMSO solutions are due to the formation of MDA . This is artificially formed through the hydrolysis of MDI, caused by traces of water that are always present in DMSO . These findings indicate that DMSO is an inappropriate solvent and should therefore not be used in any in vitro study with diisocyanates . EGDE may be a suitable replacement . The positive test results reported so far for DMSO solutions of MDI are thus only of limited relevance for risk evaluation. Mutat Res, 1998 Jan 30, 412(2), 145 - 54 Laser pyrolysis products: sampling procedures, cytotoxic and genotoxic effects; Stocker B et al.; The use of lasers in medical applications has grown enormously in the last few years . Recent chemical analysis of the laser pyrolysis products revealed that aerosols generated by pyrolytic decomposition of tissue could be health hazards . Therefore we analysed the genotoxic and mutagenic effects of laser pyrolysis products from different types of porcine tissue . The tissues were irradiated with a surgical CO2 laser and the generated aerosols were sampled as particulate fractions as well as low and highly volatile fractions . Then human leukocytes were incubated with the pyrolysis products and subjected to the comet assay . The results of the comet assay indicated the pyrolysis products being inducers of DNA damage . The ability to induce genotoxic effects turned out to be strongly dependent on the type of tissue that had been irradiated during laser treatment . To check whether the pyrolysis products also have mutagenic properties the Salmonella mutagenicity assay was performed . The particulate aerosol fractions of skin, muscle tissue and liver tissue clearly proved to be mutagenic in TA98 in the presence of S9 mix . There was no mutagenic effect detectable without metabolic activation . In conclusion, our experiments showed that the laser pyrolysis products originating from porcine tissues induced very potent genotoxic as well as mutagenic effects and therefore they could be potential health hazards for humans. Mutat Res, 1998 Jan 30, 412(2), 115 - 30 Comparison of responses of base-specific Salmonella tester strains with the traditional strains for identifying mutagens: the results of a validation study; Gee P et al.; The ability of a TA7000 series of Salmonella his- mutant tester strains to detect mutagens as classified by the traditional tester strains (TA100, TA98, TA1535, TA1537, TA97, TA102 and TA104) was evaluated using 30 coded chemicals, 5 of which were duplicates with different code numbers . The TA7000 series of tester strains were TA7001, TA7002, TA7003, TA7004, TA7005 and TA7006, each of which reverts by a specific base substitution . In addition, each chemical was tested in a mixture of the base-specific strains (the Mix), plus the traditional strains, TA98 and TA1537 . A liquid version of the Salmonella mutagenicity assay was performed in microtiter plates to allow partial automation for increased throughput . The results were compared to those in the National Toxicology Program (NTP) database, which were obtained from the traditional strains in the preincubation assay . In the two strains common to both protocols, TA98 and TA1537, the agreement was 80% and 85%, respectively . When compared to the NTP results for TA100, the Mix gave a 72% concordance, while the addition of the frameshift tester strain, TA98, increased the agreement to 76% . The overall agreement on positive or negative classifications of mutagenicity was 88% for the 25 chemicals tested . There were three notable exceptions to the overall agreement . Benzaldehyde was detected as a mutagen in TA7005 in contrast to its classification as a non-mutagen in the NTP database . This does not necessarily contradict the NTP results because the base-specific strains may respond to different mutagens . Two weak mutagens in the NTP database, 1-chloro-2-propanol and isobutyl nitrite, were not detected as mutagens in the base-specific new strains in the liquid protocol . While there are a number of major differences in the two assays, it was concluded that the results from each procedure are comparable. Cell Mol Life Sci, 1998 Feb, 54(2), 143 - 7 Specific recombinogenic activity of a new polyene antibiotic; Vachkova R et al.; A new antibiotic from Streptomyces sp., tetrapol A159, active against various fungi, a promising compound for the control of plant diseases, was studied for its genotoxic effects . It was produced at the Institute of Microbiological Preparations for Agriculture, Sofia, Bulgaria . The chemical was tested in three different test systems: a bacterial system, the Ames test for point mutations, the micronucleus test in bone marrow cells of rats for chromosomal aberrations and the fungal system of Aspergillus nidulans for mitotic recombination and aneuploidy . No increase in histidine revertants was observed in any of the TA100, TA98, TA1535 and TA1537 strains of Salmonella at concentrations ranging from 1 to 4000 mg/plate . The results were also negative in the micronucleus test of bone marrow cells at concentrations from 124 to 600 mg/kg b.w., whereas a statistically significant threefold increase of mitotic crossovers was found in Aspergillus, at concentrations from 0.5 to 2.5 mg/ml. Rev Sci Tech, 1997 Apr, 16(1), 83 - 90 {The risk of transmission of salmonellae in poultry farming: detection and prevention in Europe}; Humbert F et al.; While salmonellas can cause disease problems among poultry, they remain essentially a concern for public health, as a cause of outbreaks of food poisoning . The principal site of multiplication of these bacteria is the digestive tract, particularly the caecum, which may result in widespread contamination of the environment . The pathogenicity of salmonellas depends on the invasive properties and the ability of the bacteria to survive and multiply within cells, particularly macrophages . These properties are the source of vertical transmission which, in the case of survival of the embryo, can result in contamination of a flock or, in the case of embryonic mortality, can result in an explosion of contaminated eggs . Salmonella infection can be diagnosed by isolating the bacteria and/or serological testing of the flock . European Union Directive 92/117/EC, modified by Directive 97/22/EC, stipulates either the destruction of infected flocks of breeding birds, or decontamination of the flock in an effective way, before normal trade in products can be resumed . Noteworthy examples of effective measures suitable for prophylaxis of Salmonella infection in poultry flocks include the slaughter of infected breeding stock, the creation of sanitary barriers at building entrances, heat treatment of feed, the use of competitive exclusion, selection of breeds genetically resistant to Salmonella, and occasional vaccination and antibiotic treatment . However, the most effective means of reducing food poisoning remains adequate cooking of food and maintenance of the cold chain. Tijdschr Diergeneeskd, 1998 Feb 15, 123(4), 114 - 7 {Pustular dermatitis in veterinarians following delivery in farm animals; an occupational disease}; Visser IJ; OBJECTIVE: To assess the prevalence of contact dermatitis after deliveries in cattle or sheep among veterinarians . DESIGN: Retrospective . SETTING: Provinces of Groningen, Friesland, and Drenthe, The Netherlands . METHODS: By means of a short inquiry 310 veterinarians were asked whether and how often they had experienced pustular dermatitis after deliveries in cattle and sheep and what course the dermatitis had run . They were also asked about details of the deliveries (type of animal, condition of the foetus, course of the partus), about microbiological investigation, preventive measurements and therapy . RESULTS: The response to the questionnaires was 24.5% . One or more episodes of pustular dermatitis on an arm after a delivery in cattle or sheep was noticed by 62 (81.5%) of the 76 respondents . Sometimes it was associated with secondary symptoms like headache, fever and lymphadenitis . Listeria monocytogenes (7 times out of 13) and Salmonella dublin (4/13) were the agents cultured most often . CONCLUSION: Contact dermatitis after deliveries in cattle or sheep occurs frequently as an occupational disease of veterinarians. Eur Radiol, 1998, 8(2), 295 - 7 Mycotic aneurysm rupture of the descending aorta; Gufler H et al.; A 69-year-old diabetic male with salmonella bacteremia developed hypovolemic shock and swelling of the neck . A CT examination revealed massive mediastinal hemorrhage extending into the neck soft tissues caused by false aneurysm rupture of the descending thoracic aorta . Aortography showed continuous extravasation from a large leak at the medial side of the descending thoracic aorta . Although surgical intervention was immediately performed, the patient died 3 weeks later from multiple-organ failure . In this report, CT and angiographic findings of mycotic aneurysm rupture are presented and a review is given. J Ethnopharmacol, 1998 Feb, 60(1), 79 - 84 Antibacterial activity of East African medicinal plants; Fabry W et al.; In an ethnopharmacological survey, extracts of the six East African medicinal plants Entada abyssinica (stem bark), Terminalia spinosa (young branches), Harrisonia abyssinica (roots), Ximenia caffra (roots), Azadirachta indica (stem bark and leaves), and Spilanthes mauritiana (roots and flowers) were tested against 105 strains of bacteria from seven genera (Staphylococcus, Enterococcus, Pseudomonas, Escherichia, Klebsiella, Salmonella, Mycobacterium) . The minimum inhibitory concentration reached by 50% (MIC50%) and 90% (MIC90) of the strains for the extracts of E . abyssinica, T . spinosa, X . caffra, and A . indica (stem bark) ranged from 0.13-8 mg/ml and from 0.5 to > 8 mg/ml, respectively . Their minimum bactericidal concentration by 50% (MBC50%) and MBC90% were all between 0.5 and > 8 mg/ml . H . abyssinica, A . indica (leaves), and S . mauritiana (roots and flowers) had MIC and MBC values > or = 8 mg/ml . Mycobacteria were not inhibited at extract concentrations of 0.5-2 mg/ml . It is concluded that plant extracts with low MIC and MBC values may serve as sources for compounds with therapeutic potency. Vet Immunol Immunopathol, 1997 Dec 12, 60(1-2), 111 - 30 Analysis of the immune response in sheep efferent lymph during Salmonella abortusovis infection; Gohin I et al.; The efferent lymph duct of the ovine prescapular lymph node was cannulated, and Salmonella abortusovis (SAO), a specific pathogen for sheep inducing abortion and mortality of newborn lambs, was inoculated by the subcutaneous route in this lymph node drained area . While the prescapular lymph node draining the inoculation site represented an efficient barrier for the vaccinal SAO Rv6 strain spreading, SAO 15/5 virulent bacteria were steadily detected in efferent lymph of infected sheep . The inoculation of the virulent strain of SAO induced a greater increase of the cell output than did the attenuated vaccinal strain, but proportions of blast cells appearing in the efferent lymph were similar in both cases . Flow cytometry analysis showed that B and T cell outputs were both increased during SAO infections, but while T cell subset proportions slightly decreased, B cell percentages significantly rose, and, at the peak response, almost all of the lymphoblast cells were activated B cells . Typical antibody profiles characteristic of a primary immune response were observed, and antibody titres were greater in the efferent lymph of animals inoculated with the virulent strain of SAO . Many of the cytokine mRNAs we investigated were steadily detected by RT-PCR in efferent lymph cells of control sheep, but frequencies of detection of IL-2, IFN gamma, IL-1 beta and TNF alpha mRNAs were augmented in efferent lymph cells following inoculation of both SAO virulent or vaccinal strains . IL-10 and IL-8 mRNAs could only be detected after a SAO inoculation, while detection of IL-4 mRNAs was increased only in efferent lymph cells from SAO virulent strain-infected sheep . The efferent lymph cannulation technique thus appeared a very powerful way to study the in vivo development of the immune response to SAO, in its natural host, the sheep. Avian Dis, 1998 Jan-Mar, 42(1), 146 - 53 Mutation rate of avian intestinal coliform bacteria when pressured with fluoroquinolones; Medders WM et al.; The purpose of this study was to determine the rate at which resistance developed in avian coliform bacteria when exposed to nalidixic acid, sarafloxacin, or enrofloxacin . In in vitro studies, the rates of mutation of avian isolates of Escherichia coli and Salmonella were determined following nalidixic acid, sarafloxacin, or enrofloxacin pressure . The rates of mutation were similar for nalidixic acid and sarafloxacin, whereas a lower rate of mutation was seen after enrofloxacin pressure . In in vivo studies, the quinolones were administered in the drinking water to broiler chickens at a concentration of 40 ppm for five consecutive days . Samples of feces were inoculated onto appropriate media and the frequency of resistance was determined . The frequency rates of resistance to nalidixic acid and sarafloxacin were similar . Enrofloxacin-medicated birds did not develop enrofloxacin-resistant coliform bacteria . The in vitro and in vivo data appear to correlate. Avian Dis, 1998 Jan-Mar, 42(1), 67 - 71 A survey for Salmonella by drag swabbing manure piles in California egg ranches; Riemann H et al.; A cross-sectional study was conducted between August 1995 and November 1996 . Sixty California egg-producing ranches were chosen at random; 39 ranches agreed to participate in the study . The surface of the manure pile in one house on each ranch was sampled by drag swabbing . The drag swabs were tested for Salmonella using a most probable number procedure that had a detection level of one to five Salmonella per drag swab . In 12 ranches (32.4%), the drag swabs were negative for Salmonella; the remaining had Salmonella counts in the range of 1 to over 1700 per swab . Twenty-two different serotypes were found . Salmonella heidelberg and Salmonella cerro represented the majority of the typed isolates . Salmonella enteritidis (SE) was found on only one ranch . This study found SE to be rare in California egg ranches, which implies that these ranches are not a major source of S . enteritidis. Avian Dis, 1998 Jan-Mar, 42(1), 45 - 52 Airborne horizontal transmission of Salmonella enteritidis in molted laying chickens; Holt PS et al.; Salmonella enteritidis is currently thought to be transmitted principally through contact with infected individuals and ingestion of fecally contaminated materials . The present study was undertaken to determine if S . enteritidis could be spread in chickens by the airborne route and if induced molting could affect this mode of transmission . To test for airborne transmission, hens were placed in two rows of cages, the rows separated from each other by 1 m . One row of hens was challenged with S . enteritidis, whereas the other row remained unchallenged but exposed to the room air . Ventilation delivered within the room provided an even air distribution within the area and minimized directional air flow toward any set of cages . In Expt . 1, 4 of 12 and 9 to 12 exposed molted hens became infected with S . enteritidis after 3 and 8 days of exposure, respectively, compared with 1 of 12 and 0 of 12 unmolted hens sampled on the same days . Similar S . enteritidis levels were detected circulating in the air in the two rooms housing the hens . Expts . 2 and 3 examined airborne transmission in molted hens only . In Expt . 2, 2 of 12 exposed hens became infected with S . enteritidis at 3 days postchallenge, and this increased to 12 of 12.1 wk later . In Expt . 3, exposed hens were again housed in cages 1 m from challenged hens but were placed in every other cage to prevent transmission through contact with hens in adjacent cages . At day 3 post challenge, 0 of 12 exposed hens were culture positive for S . enteritidis, and this increased to only 3 of 10 positive hens at day 10 . Large numbers of S . enteritidis shed by the molted challenged hens were recovered from the floors beneath the cages . These results indicated that, contrary to the generally held beliefs regarding organism spread, airborne transmission of S . enteritidis can occur and induced molting can provide the impetus for this event . As was observed previously, rapid dissemination of the organism to other members of the flock resulted through bird-to-bird contact. Vet Clin North Am Food Anim Pract, 1998 Mar, 14(1), 151 - 64 Pathogen Reduction and Hazard Analysis and Critical Control Point (HACCP) systems for meat and poultry . USDA; Hogue AT et al.; The United States Department of Agriculture (USDA) Food Safety Inspection Service (FSIS) adopted Hazard Analysis and Critical Control Point Systems and established finished product standards for Salmonella in slaughter plants to improve food safety for meat and poultry . In order to make significant improvements in food safety, measures must be taken at all points in the farm-to-table chain including production, transportation, slaughter, processing, storage, retail, and food preparation . Since pathogens can be introduced or multiplied anywhere along the continuum, success depends on consideration and comparison of intervention measures throughout the continuum . Food animal and public health veterinarians can create the necessary preventative environment that mitigates risks for food borne pathogen contamination. Afr J Med Med Sci, 1996 Dec, 25(4), 373 - 5 Antimicrobial activity of some medicinal plants extracts on Escherichia coli, Salmonella paratyphi and Shigella dysenteriae; Omoregbe RE et al.; The antimicrobial activity of three plants extracts--Momordica charantia, Alstonia boonei, and Ocimum bacilicum on pure and viable cultures of Escherichia coli, Salmonella paratyphi and Shigella dysenterae was examined . Cold maceration method of extraction using 95% ethanol was used for the extraction of the active constituents of the leaves . Filter paper disks which were 6 mm in diameter were used for sensitivity testing . Results showed that the extracts from the leaves of the three plants have some antimicrobial properties against the test organisms which suggest their future possible commercial therapeutic use, although this is a preliminary study. Zentralbl Hyg Umweltmed, 1998 Feb, 200(5-6), 531 - 41 {Mutagenicity of mixtures of halogenated aliphatic hydrocarbons and polycyclic aromatic hydrocarbons in the Ames test with TA98 and TA100}; Kevekordes S et al.; Within the framework of the assessment of the genotoxic potential of environment samples the Salmonella-microsome-test (Ames-test) is often used as a screening-test . It is one of the most applied biotest systems and possesses a large scientific acceptance . Because most environment samples are mixtures of various substances, possible effects resulting from the combination should be taken into account with regard to the mutagenic potential . In this context we investigated eight polycyclic aromatic hydrocarbons each combined with six halogenated aliphatic hydrocarbons as to their mutagenicity in the Salmonella-microsome-test with TA98 and TA100 . For an exogenous metabolizing system, Arochlor 1254 induced rat liver S9-mix was used . Benz-a-pyrene in combination with bromodichloromethane (Ames neg . in TA98 and TA100 +S9) showed an increase in the number of the revertants up to 25% in TA98 and TA100 (+S9) . Carbon tetrachloride (Ames neg . in TA98 and TA100 +S9) showed in TA100 (+S9) an increase in the number of the revertants of 18% at most . In the combination 3-methylcholanthrene with dichloromethane the number of revertants in TA98 (+S9) increased by 25% and in TA100 (+S9) by 18% . Hexachloroethane (weakly mutagenic in TA98 +S9) in combination showed in TA98 (+S9) a slightly increased number of revertants with benz-a-pyrene as well with 3-methylcholanthrene . All the other substances tested (chrysene, phenanthrene, anthanthrene, dibenz-a, i-pyrene, triphenylene, fluoranthene) in combination with either tetrachloroethylene or trichloroethene did not cause an increase in mutagenicity. J Immunol, 1998 Apr 1, 160(7), 3480 - 6 Activation of caspase 3 (CPP32)-like proteases is essential for TNF-alpha-induced hepatic parenchymal cell apoptosis and neutrophil-mediated necrosis in a murine endotoxin shock model; Jaeschke H et al.; Endotoxin (ET)-induced liver failure is characterized by parenchymal cell apoptosis and inflammation leading to liver cell necrosis . Members of the caspase family have been implicated in the signal transduction pathway of apoptosis . The aim of this study was to characterize ET-induced hepatic caspase activation and apoptosis and to investigate their effect on neutrophil-mediated liver injury . Treatment of C3Heb/FeJ mice with 700 mg/kg galactosamine (Gal) and 100 microg/kg Salmonella abortus equi ET increased caspase 3-like protease activity (Asp-Val-Glu-Asp-substrate) by 1730 +/- 140% at 6 h . There was a parallel enhancement of apoptosis (assessed by DNA fragmentation ELISA and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay) . In contrast, activity of caspase 1 (IL-1beta-converting enzyme)-like proteases (Tyr-Val-Ala-Asp-substrate) did not change throughout the experiment . Caspase 3-like protease activity and apoptosis was not induced by Gal/ET in ET-resistant mice (C3H/HeJ) . Furthermore, only murine TNF-alpha but not IL-1alphabeta increased caspase activity and apoptosis . Gal/ET caused neutrophil-dependent hepatocellular necrosis at 7 h (area of necrosis, 45 +/- 3%) . Delayed treatment with the caspase 3-like protease inhibitor Z-Val-Ala-Asp-CH2F (Z-VAD) (10 mg/kg at 3 h) attenuated apoptosis by 81 to 88% and prevented liver cell necrosis (< or = 5%) . Z-VAD had no effect on the initial inflammatory response, including the sequestration of neutrophils in sinusoids . However, Z-VAD prevented neutrophil transmigration and necrosis . Our data indicate that activation of the caspase 3 subfamily of cysteine proteases is critical for the development of parenchymal cell apoptosis . In addition, excessive hepatocellular apoptosis can be an important signal for transmigration of primed neutrophils sequestered in sinusoids. Epidemiol Infect, 1998 Feb, 120(1), 29 - 35 A community outbreak of Salmonella berta associated with a soft cheese product; Ellis A et al.; In September 1994, a complaint was registered at a public health unit concerning a cheese product . In addition, public health laboratories in Ontario reported an increase in the number of isolates of Salmonella berta from patients with diarrhoeal illness . A clinical, environmental and laboratory investigation was initiated to determine the nature of this outbreak . Isolates of Salmonella berta were compared using large fragment genomic fingerprinting by pulsed-field gel electrophoresis (PFGE) . By late October, 82 clinical cases had been identified including 35 confirmed, 44 suspected and 3 secondary . The investigation linked illness to consumption of an unpasteurized soft cheese product produced on a farm and sold at farmers' markets . Subtyping results of patient, cheese and chicken isolates were indistinguishable, suggesting that the cheese was contaminated by chicken carcasses during production . The outbreak illustrates the potential role of uninspected home-based food producers and of cross-contamination in the transmission of foodborne bacterial pathogens. Arch Microbiol, 1998 Feb, 169(2), 113 - 9 Effects of the insertion of a nonapeptide from murine IL-1beta on the immunogenicity of carrier proteins delivered by live attenuated Salmonella; Chen I et al.; A nonapeptide from IL-1beta has been reported to be an immunostimulant and adjuvant . To investigate the possibility of enhancing the immunogenicity of recombinant antigens delivered by live-attenuated Salmonella strains, we inserted an oligonucleotide coding for the nonapeptide from murine IL-1beta into the genes of three model proteins: LamB, MalE, and flagellin . The hybrid proteins were expressed and delivered in vivo by Salmonella aroA strains, and serum antibody responses were analyzed . The results showed that the nonapeptide induced an increase in the immune response against Salmonella-delivered flagellin, measured on day 28 post-immunization . However, the adjuvant effect was lost by day 42 . In no case was an adjuvant effect detected for Salmonella-delivered LamB or MalE . Thus, by comparing the immune responses raised by purified MalE with and without the peptide, we investigated whether the insertion of the peptide affected the immunogenicity of the protein itself . Also in this case, a modest adjuvant effect was shown only after primary immunization and when very low doses of antigen were used . In conclusion, the immunomodulatory properties of the IL-1beta peptide can also be detected when it is delivered in vivo by Salmonella; however, the effect is modest and antigen-dependent. J Biochem Mol Toxicol, 1998, 12(3), 143 - 9 Streptozotocin may provide protection against subsequent oxidative stress of endotoxin or streptozotocin in rats; Omar HM et al.; Endotoxin lipopolysaccharide (LPS) and streptozotocin-induced diabetes are known to cause oxidative stress in vivo . There is some evidence that a sublethal dose of LPS provides protection against subsequent oxidative stress . Because of its wide use as a diabetogenic agent, this study was undertaken to determine if streptozotocin can likewise provide a protective effect against further oxidative stress in rats . Female Sprague-Dawley rats were given streptozotocin (50 mg/kg intraperitoneally once) prior to exposure to either bacterial endotoxin from Salmonella abortus equii (5 mg/kg intraperitoneally) or three additional daily doses of streptozotocin (50 mg/kg intraperitoneally) . One week after LPS or streptozotocin treatments, oxidative stress was determined by measuring changes in antioxidant activity (glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, glutathione S-transferase, and gamma-glutamyltranspeptidase) and in concentrations of glutathione, nitrite, and thiobarbituric acid reactants in liver, kidney, intestine, and spleen . High levels of some antioxidants in the LPS-control and streptozotocin-control rats, in contrast to normal levels found in diabetes + LPS and multidose-streptozotocin rats, suggest that streptozotocin, like LPS, may confer a protective effect against subsequent oxidative stress. J Reconstr Microsurg, 1998 Jan, 14(1), 13 - 6 Free vascularized fibular graft in the treatment of Salmonella typhi osteomyelitis of the distal radius; Taniguchi Y et al.; The authors report a rare case of Salmonella typhi osteomyelitis involving the distal radius . The patient was treated successfully by wide resection and reconstruction of the distal radius with a vascularized fibular transfer . Local recurrence of infection did not occur . The free vascularized fibular graft is an effective procedure for the treatment of osteomyelitis of the distal radius. J Zoo Wildl Med, 1997 Dec, 28(4), 368 - 77 Health evaluation of free-ranging and hand-reared macaws (Ara spp.) in Peru; Karesh WB et al.; As part of ongoing ecological studies and reproduction enhancement efforts for macaws in southwestern Peru, a health survey of parent- and hand-reared scarlet macaws (Ara macao) and blue and gold macaws (Ara ararauna) was conducted in 1994 . Thirty-three birds were examined during handling procedures, and blood samples were collected from 27 (9 parent reared, 18 hand reared) for laboratory analysis . All but one bird appeared to be in good condition, with no abnormality noted during physical examination . Hematology, plasma chemistries, and plasma vitamin and mineral levels were studied and correlated with the results of bacterial and viral serology . Positive antibody titers for Salmonella and psittacine herpesvirus were found . These diseases have the potential to affect wildlife population dynamics, and Salmonella may have public health significance . Serological tests for avian influenza, infectious laryngotracheitis, paramyxovirus-1, -2, -3, polyoma virus, chlamydiosis, and aspergillosis were negative . Differences in disease prevalence were found between rearing situations. P N G Med J, 1995 Dec, 38(4), 325 - 31 A review of the current status of enteric vaccines; Levine MM et al.; Much progress has been made in developing vaccines against the most important enteric infections . Two new vaccines against typhoid fever (oral Ty21a and parenteral Vi polysaccharide) have been licensed in many countries . Newer, more sophisticated typhoid vaccines undergoing clinical testing include recombinant attenuated Salmonella typhi strains and Vi polysaccharide-carrier-protein conjugate vaccines . Two inactivated oral cholera vaccines, consisting of inactivated Vibrio cholerae O1 bacteria alone or in combination with B subunit of cholera toxin, each conferred 50-53% protection over three years in a field trial in Bangladesh where subjects were immunized with a three-dose regimen . An engineered live oral cholera vaccine, strain CVD 103-HgR, has been shown in extensive clinical trials to be well tolerated by children and adults in less developed countries and highly immunogenic following administration of just a single oral dose; a large-scale field trial of the efficacy of this vaccine is underway . In experimental challenge studies in volunteers, a single dose of CVD 103-HgR confers significant protection against challenge with wild-type V . cholerae O1 of either classical or El Tor biotype and either Inaba or Ogawa serotype . Several candidate vaccines against Shigella and enterotoxigenic Escherichia coli are in clinical trials . A multivalent rotavirus vaccine (rhesus reassortant vaccine) is undergoing extensive field testing in developed and less developed countriesPIP: The development of safe, effective vaccines to prevent diseases due to rotavirus, enterotoxigenic Escherichia coli, enteropathogenic E . coli, Shigella, and Vibrio cholerae O1 would markedly reduce the burden of diarrheal diseases in Third World countries . This review concentrates on vaccines that have already been licensed, that have been evaluated in controlled trials of efficacy, or that have entered clinical trials to assess their safety and immunogenicity . Two new vaccines against typhoid fever have been licensed . Newer, more sophisticated typhoid vaccines undergoing clinical testing include recombinant attenuated Salmonella typhi strains and Vi polysaccharide-carrier-protein conjugate vaccines . Inactivated oral cholera vaccines consisting of inactivated Vibrio cholerae O1 bacteria alone or in combination with B subunit of cholera toxin conferred 50-53% protection in a field trial in Bangladesh . An engineered live oral cholera vaccine, strain CVD 103-HgR, has been shown in extensive clinical trials to be well tolerated and highly immunogenic after a single oral dose . In experimental challenge studies, a single dose of CVD 103-HgR conferred significant protection against challenge with wild-type V . cholerae O1 . Several candidate vaccines against Shigella and enterotoxigenic E . coli are in clinical trials . Finally, a multivalent rotavirus vaccine (rhesus reassortant) is undergoing extensive field testing . P N G Med J, 1995 Dec, 38(4), 315 - 9 The role of the laboratory in the diagnosis and management of typhoid fever; Clegg A; In typhoid-endemic areas the results obtained from the laboratory are important in confirming the clinical diagnosis of typhoid and may also contribute to decisions made on the management and treatment of typhoid cases . Isolation of Salmonella typhi remains the gold standard, with culture from bone marrow aspirate or a combination of specimens from other body sites resulting in the greatest sensitivity . Antibody detection techniques may still provide valuable information, but only if the results are interpreted in the context of the background antibody levels in the local population . None of the available antigen detection techniques have been consistently demonstrated to be of diagnostic value and a recently developed polymerase chain reaction (PCR) for the detection of Salmonella typhi has yet to undergo a full-scale clinical evaluation . The initial identification of chronic typhoid carriers relies upon the detection of elevated Vi capsular antibody levels, but seeking out chronic carriers will be of limited value in controlling the spread of typhoid in areas where transmission is principally mediated by convalescent excretors . Whilst resistance of Salmonella typhi to antibiotics has emerged as an increasing problem in some areas of the world, it is still uncommon in isolates from Papua New Guinea . However, monitoring of antibiotic susceptibility patterns will ensure that signs of developing resistance are detected early and that the appropriate action is taken. P N G Med J, 1995 Dec, 38(4), 300 - 4 The new problem of typhoid fever in Papua New Guinea: how do we deal with it? Passey M. This paper reviews some of the issues relating to typhoid fever in Papua New Guinea . Before the mid-1980s only sporadic cases of typhoid were reported but it is now one of the greatest public health problems in the highlands and some urban areas . In one study near Goroka an annual incidence rate of 1208 per 100,000 people was found, with settlers from other areas at greater risk than the local landowners . Problems relating to management included differentiation from other diseases, the limitations of the Widal test and poor compliance among outpatients . In Papua New Guinea it appears that transmission is largely from person to person, with little evidence for water-borne transmission . The prolonged convalescent excretion of Salmonella typhi and the difficulties this poses for control of the disease are discussed . Prevention will only be achieved in the long term by improvements in hygiene and sanitation, though more immediate control could be achieved by vaccination with an appropriate vaccinePIP: Few cases of typhoid fever were reported in Papua New Guinea (PNG) before 1960 and only sporadic cases were reported during the 1960s . However, typhoid fever has now become a major public health problem in the country, endemic throughout the Highlands Region and in some of the larger coastal towns such as Port Moresby . In 1993 and 1994, there were 4485 and 4551 people, respectively, reported to have been admitted with typhoid fever throughout PNG, with 87% and 73% of these cases, respectively, occurring in the Highlands Region . The vast majority of the remainder of patients were in the National Capital District, Central, or Morobe Provinces . No data are available on the number of outpatient cases . The transmission of typhoid fever in PNG appears to be mainly from person to person, with little evidence of water-borne transmission . Problems posed by the prolonged convalescent excretion of Salmonella typhi are discussed . Typhoid fever will be prevented over the long term by improvements in hygiene and sanitation, although more immediate control could be achieved through vaccination with an appropriate vaccine . Arch Intern Med, 1998 Mar 23, 158(6), 633 - 8 Typhoid fever in the United States, 1985-1994: changing risks of international travel and increasing antimicrobial resistance; Mermin JH et al.; BACKGROUND: Typhoid fever is a potentially fatal illness common in the less industrialized world . In the United States, the majority of cases occur in travelers to other countries . METHODS: We reviewed surveillance forms submitted to the Centers for Disease Control and Prevention, Atlanta, Ga, for patients with culture-confirmed typhoid fever between 1985 and 1994 . RESULTS: The Centers for Disease Control and Prevention received report forms for 2445 cases of typhoid fever . Median age of patients was 24 years (range, 0-89 years) . Ten (0.4%) died . Seventy-two percent reported international travel within the 30 days before onset of illness . Six countries accounted for 80% of cases: Mexico (28%), India (25%), the Philippines (10%), Pakistan (8%), El Salvador (5%), and Haiti (4%) . The percentage of cases associated with visiting Mexico decreased from 46% in 1985 to 23% in 1994, while the percentage of cases associated with visiting the Indian subcontinent increased from 25% in 1985 to 37% in 1994 . The incidence of typhoid fever in US citizens traveling to the Indian subcontinent was at least 18 times higher than for any other geographic region . Complete data on antimicrobial susceptibility to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole were reported for 330 (13%) Salmonella Typhi isolates . Isolates from 1990 to 1994 were more likely than isolates from 1985 to 1989 to be resistant to any of these antimicrobial agents (30% vs 12%; P<.001) and to be resistant to all 3 agents (12% vs 0.6%; P<.001) . CONCLUSIONS: American travelers to less industrialized countries, especially those traveling to the Indian subcontinent, continue to be at risk for typhoid fever . Antimicrobial resistance has increased, and a quinolone or third-generation cephalosporin may be the best choice for empirical treatment of typhoid fever. Adv Virus Res, 1998, 50, 141 - 82 Core particles of hepatitis B virus as carrier for foreign epitopes; Ulrich R et al.; To be effective as vaccines, most monomeric proteins and peptides either require chemical coupling to high molecular weight carriers or application together with adjuvants . More recently, recombinant DNA techniques have been used to insert foreign epitopes into proteins with inherent multimerization capacity, such as parti