J Biol Chem, 1996 Jan 19, 271(3), 1527 - 33 Analysis by surface plasmon resonance of the influence of valence on the ligand binding affinity and kinetics of an anti-carbohydrate antibody; MacKenzie CR et al.; The kinetics of ligand binding by Se155-4, an antibody specific for the Salmonella serogroup B O-polysaccharide, were studied by surface plasmon resonance . Because trace amounts of oligomers in Fab and single-chain antibody variable domain (scFv) preparations resulted in biphasic binding profiles that were difficult to analyze, all kinetic measurements were performed on purified monomeric fragments and, for certain mutant scFv, dimeric forms . Results obtained with monomeric forms indicated that the relatively low affinity of the antibody was due to rapid dissociation (koff approximately 0.25 s-1) . Dimeric forms generally showed off-rates that were approximately 20-fold slower and a 5-fold increase in association rate constants to approximately 2 x 10(5) M-1 s-1 . Although the association phases for scFv dimers showed good curve fitting to a one component interaction model, the dissociation phases were biphasic, presumably because the availability and accessibility of sites on the antigen always leads to some monovalent attachment . The fast off-rate for dimers was the same as the monomer off-rate . Se155-4 IgG off-rates were very similar to those observed for scFv dimer, whereas the onrate was the same as that obtained with Fab and scFv monomer. Mutat Res, 1996 Jan 17, 349(1), 1 - 20 Mutation spectra of chemical fractions of a complex mixture: role of nitroarenes in the mutagenic specificity of municipal waste incinerator emissions; DeMarini DM et al.; Using an ion-exchange procedure coupled to a microsuspension Salmonella assay, we fractionated the dichloromethane-extractable particulate organics emitted by a municipal waste incinerator . Most (80-95%) of the mutagenic activity resided in the neutral/base fraction; however, the polar neutral fraction accounted for 12% of the direct-acting mutagenic activity . The mutagenic potencies of the whole extract and the various fractions were 4-15 times greater in the absence than in the presence of S9 . Results with strains deficient in classical nitroreductase (TA98NR) and transacetylase (TA98/1,8-DNP6) indicated that a majority of the direct-acting mutagenicity was due to nitroarenes . This was confirmed by bioassay-directed subfractionation of the neutral/base faction by a cyanopropyl/HPLC method . The mutations in -3,000 revertants (approximately 400 each induced in TA98 by the whole extract, the neutral/base and polar neutral fractions from the ion-exchange column and 3 of the neural/base subfractions from the HPLC column; along with 200 revertants each induced by the model nitroarene 1-nitropyrene (1NP) in strains TA98, TA1538 and TA100) were analyzed by probe hybridization and PCR/DNA sequence analysis . The results indicated that nitroarenes such as 1NP that eluted in the neutral/base fraction accounted for at least 50% of the direct-acting mutagenicity and induced only a hotspot 2-base deletion in the sequence (CG)4 in TA98 . In contrast, most of the complex frameshifts (a frameshift with a flanking base substitution) induced by the whole extract were induced by nitroarenes other than 1NP that were activated by transacetylation and that eluted in the polar neutral fraction . This study (1) identifies nitroarenes as an important contributor to the mutagenic activity of the emissions from municipal waste incinerators; (2) confirms our previous conclusion that the mutation spectrum of a complex mixture reflects the dominance of particular classes of chemical mutagens within the mixture; and (3) demonstrates the possibility of isolating certain chemical fractions of a complex mixture that induce certain classes of mutations produced by the whole, unfractionated mixture. J Immunol, 1996 Jan 15, 156(2), 663 - 9 IL-15 is a novel growth factor for murine gamma delta T cells induced by Salmonella infection; Nishimura H et al.; We have previously shown evidence for the early recruitment of gamma delta T cells during the disease course of primary infections with Listeria monocytogenes or Salmonella choleraesuis in mice . Since gamma delta T cells at this stage of the disease do not produce IL-2, the growth factor for the gamma delta T cells remains unknown . IL-15 is a novel cytokine that uses beta- and gamma-chain of IL-2R for signal transduction, and is produced by activated monocytes/macrophages . In this study, we investigated the proliferative activity of IL-15 for gamma delta T cells appearing after primary infection with S . choleraesuis 31N-1 . The gamma delta T cells, which expressed beta- and gamma-chains of IL-2R, proliferated in the presence of rIL-15 and produced appreciable levels of gamma-IFN and IL-4 . Addition of anti-IL-2R beta mAb significantly inhibited the IL-15-induced proliferation of the gamma delta T cells . Furthermore, the gamma delta T cells produced gamma-IFN in response to monocyte/macrophage cell line, J774A.1 infected with S . choleraesuis, which expressed an abundant level of IL-15 mRNA . This cytokine production was inhibited significantly by anti-IL-15 Ab . Taken together, these results suggest that IL-15 derived from infected macrophages may contribute to the early activation of gamma delta T cells during salmonellosis. BMJ, 1996 Jan 13, 312(7023), 91 - 4 Large outbreak of Salmonella enterica serotype paratyphi B infection caused by a goats' milk cheese, France, 1993: a case finding and epidemiological study; Desenclos JC et al.; OBJECTIVE--To assess the magnitude of a nationwide outbreak of infection with Salmonella enterica serotype paratyphi B and identify the vehicle and source of infection . DESIGN--A case finding study of S paratyphi B infection between 15 August and 30 November 1993; a pair matched case-control study; an environmental investigation at a processing plant that produced a raw goats' milk cheese incriminated in the outbreak; phage typing and genotyping of food and human S paratyphi B isolates . SETTING--France, 15 August to 30 November 1993 . SUBJECTS--273 patients with S paratyphi B infection; 59 pairs of cases and controls matched for age, sex, and city of residence . MAIN OUTCOME MEASURES--Numbers of cases and incidence rates by region of residence and age; matched odds ratios for dairy food preferences . RESULTS--Among the 273 cases there was one death; 203 (78%) strains belonged to phage type 1 var 3 . The incidence of infection was greatest in the region where goats' milk cheese is commonly produced . Comparison of cases and controls showed a 12-fold greater risk of illness (95% confidence interval 1.6 to 92.3) from eating brand A unpasteurised goats' milk cheese . S paratyphi B isolates of phage type 1 var 3 were recovered from cheese A, goats' milk at the plant processing cheese A, and goats' milk supplied to the plant by a single farm . Genotypic IS 200 typing of food and human 1 var 3 phage type isolates showed a common IS 200 pattern . CONCLUSION--This outbreak emphasises the potential health hazards of widely distributed unpasteurised milk products in France and the need for their close bacterial monitoring. Antibiot Khimioter, 1996, 41(11), 18 - 24 {A chronobiological study of the function of the epithelial proliferative system of the murine esophagus after its infection with typhoid and the use of lomefloxacin}; Romanov IuA et al.; The rhythmical character of the function of the proliferative system of the oesophagus epithelium of mice changed after infection by Salmonella typhi and after injection of lomefloxacin to intact and infected mice . The degree of the changes depended on the exposure time . The proliferative system of the oesophagus epithelium was more resistant to the infection in the night-time than the day-time and equally resistant to the effect of lomefloxacin in both the day-time and the night-time . The proliferative system of the oesophagus epithelium of the infected mice exposed to lomefloxacin in the day-time proved to be in a noncompensated state and in the night-time it proved to be in the hyperfunctional state. Exp Clin Immunogenet, 1996, 13(3-4), 121 - 5 Gm and Km allotypes and typhoid fever; Herrera P et al.; Gm and Km allotypes of immunoglobulins were determined in children with typhoid fever (Cases), in children without infectious diseases (Con-1), and in children with fever but no Salmonella in their blood or bone marrow (Con-2) . Children were sampled from the urban population of Santiago; and they belonged to the low and low-middle socioeconomic strata . Cases had a higher frequency of {f;(-);b1,b3 or 3;(-);5,13} G1m, G2m, G3m haplotype than Con-1 and Con-2 . Con-1 and Con-2 did not differ in their Gm haplotype or Km allele frequencies, but they differed in phenotype distribution . Con-1 deviated from Hardy-Weinberg equilibrium for Km due to a lack of Km 1-1 homozygotes . The relationship among these results, the ethnic origin of Chileans, and the differential susceptibility to typhoid fever are discussed. Biochimie, 1996, 78(11-12), 935 - 43 Functional specificity of amino acid at position 246 in the tRNA mimicry domain of bacterial release factor 2; Uno M et al.; The termination of protein synthesis in bacteria requires codon-specific polypeptide release factors RF-1 (UAG/UAA specific) and RF-2 (UGA/UAA specific) . We have proposed that release factors mimic tRNA and recognize the stop codon for polypeptide release (Nakamura et al (1996) Cell 87, 147-150) . In contrast to the textbook view, genetic experiments have indicated that Escherichia coli RF-2 terminates translation very weakly at UAA while Salmonella RF-2 decodes this signal efficiently . Moreover, an excess of E coli RF-2 was toxic to cells while an excess of Salmonella RF-2 was not . These two RF-2 proteins are identical except for 16 out of 365 amino acids . Fragment swap experiments and site-directed mutagenesis revealed that a residue at position 246 is solely responsible for these two phenotypes . Upon substituting Ala (equivalent to Salmonella RF-2) for Thr-246 of E coli RF-2, the protein acquired increased release activity for UAA as well as for UGA . These results led us to conclude that E coli RF-2 activity is potentially weak and that the amino acid at position 246 plays a crucial role, not for codon discrimination, but for stop codon recognition or polypeptide release, presumably constituting an essential moiety of tRNA mimicry or interacting with peptidyltransferase centers of the ribosome. Microbios, 1996, 88(356), 169 - 76 Spontaneous binding of Vibrio cholerae to human leucocytes; Monno R et al.; Various lymphocyte subpopulations have the capacity to bind different strains of Gram-negative bacteria . The capacity of a strain of Vibrio cholerae, biotype El Tor, isolated during an outbreak of cholera, to adhere to mononuclear cells isolated from peripheral blood was evaluated . V . cholerae binds to mononuclear cells in a dose-dependent manner . The binding was 76.1% at a cells/bacteria ratio of 1:200 and significantly decreased to 43.1% at a ratio of 1:1 . The value of bound bacteria, a marker of the mean number of binding sites on the cell surface, decreased at lower cell/bacteria ratios . Studies on isolated cellular populations demonstrated that 51, 42 and 38%, respectively, of CD4+, CD8+ and B cells were bound by V . cholerae whereas monocytes exhibited a higher binding capacity . The data suggest that the percentage binding of V . cholerae to lymphocytes and monocytes was higher than the percentage found in previous studies with Gram-negative bacteria such as Yersinia enterocolitica, and Salmonella, but similar to Helicobacter pylori . The findings indicate that V . cholerae possesses multiple 'adhesins' such as fimbriae, flagella, haemagglutinins, lipopolysaccharides, and outer membrane proteins . The capacity to bind to blood lymphocytes may reflect the same capacity for the lymphocytes from the gastrointestinal associated lymphoid tissue . This cytoadherence may contribute to the uptake of V . cholerae from the gut and may contribute to activation of B cells and CD4+ lymphocytes. Acta Gastroenterol Latinoam, 1996, 26(2), 91 - 100 {Diarrhea and AIDS: more complex diagnostic techniques; better therapeutic results}; Olmos M et al.; During 17 months, 73 HIV-positive patients with diarrhea lasting at least for 14 days, were studied prospectively . The patients had stool specimen examinations negative for enteric pathogens, or positive for one of them, but with no response to specific treatment . All patients were subcomitted to digestive endoscopy and biopsies were taken for microbiological and histological studies . The etiology of the diarrhea could be established in 48 patients (66%) . In 45, the cause was an enteric infection . There was association of 2 pathogens in 11 patients, and of 3 in 1 patient . The agents found were: Cryptosporidium (24%), MAI (16%), Giardia lambila (12%), isospora belli (5%), Shigella (5%), Salmonella (5%); Entamoeba histolytica (3%), HSV (3%), tuberculosis (2%), adherent bacteria (2%) and spirochetes (2%) . In 3 patients the etiology was not infection, their diagnoses were coeliac disease, lymphoma and idiophatic colonic ulcers, respectively . In 51% of the cases only the examination of endoscopic biopsy specimens could identify the cause of the diarrhea . These results justify the use of these methods to improve diagnosis and therapeutic attempts in these patients. Acta Microbiol Pol, 1996, 45(3-4), 261 - 7 Immune response to phospholipase-A fractions of Salmonella typhi on experimental typhoid infection in mice; Punj V et al.; The intraperitoneal injection of Salmonella typhi into mice produced typhoid infection involving all the vital organs . Infection of liver was more persistent and progressive than in other organs . During the course of experimental infection, no humoral immune response was detected against phospholipase-A fractions upto 3 weeks after challenge, but significant cell mediated immunity (CMI) was found . Increased CMI response against protein antigens correlated well with the decreasing bacterial load, what suggested that CMI against proteins was important in pathogenesis of this disease. Drugs Exp Clin Res, 1996, 22(6), 317 - 21 Low-dose methotrexate in the management of Chinese patients with steroid-dependent asthma; Yew WW et al.; Nine Chinese patients with severe asthma who were dependent on a systemic oral steroid for control were given oral methotrexate at a dose of 7.5 mg on alternate days for two weeks, followed by 15 mg once weekly . Only six patients were evaluable; they had received methotrexate for 6 to 24 months . All six patients could have reduction of daily oral prednisolone dosage by 5-15 mg (mean: 10.4 mg) . Only four patients, however, had > or = 15% improvement of their best peak expiratory flow rates compared with baseline levels, though all six patients had symptomatic improvement . These beneficial effects were, however, transient and persisted only during methotrexate therapy . Four patients had liver enzyme changes and discontinuation of therapy was required in one patient . One patient also had infective spondylitis secondary to Salmonella bacteremia . Thus low-dose oral methotrexate may be useful in selected patients with severe steroid-dependent asthma with careful monitoring for response and drug toxicity. Rev Elev Med Vet Pays Trop, 1996, 49(2), 102 - 6 {Preliminary epidemiological survey on prevalences of Salmonella spp . at Bissau abattoir (Guinea-Bissau)}; Bernardo FM et al.; Considering the importance of Salmonella as a mortality and morbidity agent, in particular in children, a study on Salmonella prevalence was performed in collaboration with the Guinea-Bissau authorities through an epidemiological survey at Bissau slaughterhouse . The prevalence rate in 117 bovines slaughtered and approved for human consumption was 13.7%, with 8.5% sampled in the intestine and 5.1% in the gallbladder . Rectal swabbing in 74 live animals resulted in the isolation of S . stanleyville only . On the other hand, no strain was found in hepatic lymph nodes . These strains, some of them pathogenic for humans, are mostly called "exotic": S . bargny, S . brazzaville, S . virchow, S . rubislaw, S . brazil, S . calabar, S . havana, S . hull, S . marseille, S . shipely, S . uppsala, S . 114, 12;l,w;e,n,x . A new serotype is described: S . 28:f,m,t:- . Isolated from the caecal content, it had MSHA fimbriae (+ + + +) and 7.0 Log 10 as DL 50 . Most of these strains presented simple or multiple antibiotic resistance . They were more frequently isolated during the wet season than during the dry season. Antibiot Khimioter, 1996, 41(9), 33 - 8 {Mechanisms of resistance to quinolones and current level of sensitivity of clinically important microorganisms to ofloxacin}; Sidorenko SV et al.; The data on the mechanisms of microbial resistance to fluoroquinolones are presented . Comparison of the susceptibility levels of the microorganisms isolated on the territory of Russia showed that among the gram-negative opportunistic isolates 84 per cent was susceptible to ofloxacin, 45 per cent to ampicillin/sulbactam, 70 per cent to cefotaxime, 80 per cent to ceftazidime, 85 per cent to amikacin and 62 per cent to gentamicin . Among the Salmonella, Shigella and Vibrio cholerae isolates no strains were resistant to ofloxacin . Among the Salmonella isolates from patients more than 30 per cent was resistant to ampicillin, chloramphenicol, trimethoprim/sulmethoxasole and tetracycline . Among the Salmonella isolates 65 to 90 per cent was resistant to the antibiotics . Among the V.cholerae isolates 59 per cent was resistant to trimethoprim/sulmethoxasole. Acta Microbiol Pol, 1996, 45(2), 213 - 5 Phage types and plasmid profiles of Salmonella enteritidis strains; Gryko R; 112 strains of Salmonella enteritidis were tested according to phage typing method and plasmid profile analysis . 66 strains were classified as PT4, 29 strains as PT6 and 17 strains as PT10 . The strains were differentiated into 17 groups according to plasmid profiles. Biotherapy, 1996, 9(1-3), 105 - 8 Some properties and protective activity of specific DLE against Salmonella cholerae suis infection; Arnaudov A et al.; From a rabbit lymphoid tissue, twice immunized with a Salmonella ch . suis vaccine, was obtained a dialysable leucocyte extract (DLE) (m . w . 10,000Da; protein content 1.14 mg/ml; content of ribose 2.7 mg/ml; A260/A280 ratio 2.17 and pH 6.8) . By gel filtration on Sephadex G-25, six peaks were obtained and activity was found in peak IV . The activity of the extract was determined by a dermo-application test (DAT) on 10 cows . The protective effect was tested by a challenge with Salmonella ch . suis and Salmonella dublin pathogen strains on white mice intraperitoneally treated with DLE . The DAT proved to be positive in 8 of the 10 cows . When applied on white mice, it induced a high specific protective effect against Salmonella ch . suis (70%), but not against Salmonella dublin infection. Environ Mol Mutagen, 1996, 28(4), 434 - 42 A strategy for the application of transgenic rodent mutagenesis assays; Gorelick NJ et al.; The past several years have seen an enormous increase in the development and use of transgenic animal models to measure mutations in specific inserted reporter genes . These systems provide gene mutation data in vivo in a wide range of relevant tissues . Numerous laboratories are now using these systems with consistent results . This paper describes the unique niche that transgenic mutagenesis systems can fill in product development and registration strategies . In addition to tissue-specific mechanistic studies, transgenic assays are available to follow up mutagenic effects demonstrated in Salmonella, Escherichia coli, mouse lymphoma (L5178Y) cells, or other in vitro systems. Microbiol Immunol, 1996, 40(11), 873 - 5 An epidemiological study of Salmonella enteritidis by pulsed-field gel electrophoresis (PFGE): several PFGE patterns observed in isolates from a food poisoning outbreak; Murase T et al.; An epidemiological analysis of Salmonella enteritidis from a food poisoning was done using pulsed-field gel electrophoresis (PFGE) of BlnI- or XbaI-digested fragments of chromosomal DNA of isolates . S . enteritidis isolates obtained from 19 patients had identical PFGE patterns . Therefore, a strain giving the same pattern was considered to be the causative agent of this outbreak . In addition, four isolates that had different BlnI-digested PFGE patterns were obtained from three patients, suggesting that the observed variations in PFGE patterns might occur as the result of some point mutations of chromosomal DNA during growth or from the existence of several S . enteritidis strains from various sources . Subsequent PFGE analysis of continuously subcultured strains supported the former possibility . These observations indicate that PFGE analysis on multiple numbers of colonies from each patient are necessary for the epidemiologic investigation of S . enteritidis. Microbiol Immunol, 1996, 40(11), 799 - 811 Migration of Salmonella typhi through intestinal epithelial monolayers: an in vitro study; Kops SK et al.; This study characterizes the transmigration of enteroinvasive Salmonella typhi in vitro, using a human intestinal epithelial cell line as a model of small intestinal epithelium . C2BBe cells, a subclone of CACO-2 with a highly differentiated enterocytic phenotype, were grown to maturity on Transwell filters . S . typhi Ty2 and the vaccine strain, Ty21a, the S . typhi mutant X7344 and parent strain SB130, and S . typhimurium 5771 in logarithmic phase were introduced to the upper chamber of the filter units . Numbers of bacteria in the lower chamber, TER and permeability of the monolayer to mannitol were measured over time . Monolayers were examined by light, electron and confocal microscopy to determine the pathway of bacterial transmigration, and intracellular bacteria were estimated by gentamicin assay . Epithelial cell injury was quantified by light microscopy . S . typhi transmigrated earlier and in larger numbers than S . typhimurium, inducing marked changes in electrical resistance and permeability . Unlike S . typhimurium, S . typhi selected epithelial cells in small number and caused their death and extrusion from the monolayers leaving holes through which S . typhi transmigrated . Ty2 consistently transmigrated in larger numbers and with more injury to monolayers than Ty21a . S . typhi crosses the monolayers of C2BBe cells by a paracellular route in contrast to the transcellular pathway described for other Salmonellae . This may be related to the unique pathophysiology of S . typhi infection and the restricted host specificity of this pathogen . In these assays the vaccine strain, Ty21a, is slightly less invasive than its parent, though more invasive than S . typhimurium. J Vet Intern Med, 1996 Jan-Feb, 10(1), 7 - 14 Bone marrow cytological findings in 4 dogs and a cat with hemophagocytic syndrome; Walton RM et al.; Hemophagocytic syndrome or hemophagic histiocytosis was diagnosed in 4 dogs and 1 cat by evaluation of bone marrow aspirate smears . One of the dogs had a suspected infection with canine parvovirus and a confirmed infection with Salmonella spp, 2 dogs had presumptive diagnoses of myeloproliferative and lymphoproliferative disease, respectively, and 1 dog died without a diagnosis . The cat had hepatic lipidosis and lesions compatible with feline calicivirus infection . All animals had cytopenias involving 2 or more cell lines, and fragmented erythrocytes in the blood, along with mild to moderate increases in the number of macrophages in the bone marrow . Numerous marrow macrophages contained phagocytized hematopoietic cells . Other cytological features of the bone marrow were variable in each patient, but the degree of response in the blood was inadequate, even in those with bone marrow hyperplasia . The phagocytosis of hematopoietic elements did not appear to be caused by a primary immune disorder, but rather by the inappropriate activation of normal macrophages secondary to infectious, neoplastic, or metabolic diseases . These findings suggest that hemophagocytic syndrome may be an important factor in the development of cytopenias; the data also support the cytological evaluation of bone marrow aspirates as an aid in the diagnosis of hemophagocytic syndrome. Bacteriol Virusol Parazitol Epidemiol, 1996 Jan-Jun, 41(1-2), 43 - 6 {The sensitivity of Salmonella strains in diarrheal disease to new quinolones compared with other antimicrobial substances}; David E et al.; The sensitivity of 59 Salmonella strains isolated in children with acute diarrhoea was tested against the new quinolones like: Ciproflaxicin (CIP), Norfloxacin (NOR) and Ofloxacin (OFX), as compared to the sensitivity against same aminosides: Gentamicin (GM), Amikacin (AN) against cephalosporins: Ceftazidime (CAZ), Cefalotine (CF) and other currently used antimicrobial agents: Tetraciclin (T), Ampicilin (A), Cloramfenicol (C), Furazolidon (FU) . The majority of the studied Salmonella strains, 43 out of 59 strains, belonged to the serotype typhimurium, the most frequently serotype isolated in our geographical area . A very high percentage of Salmonella strains were sensitive against the three quinolones: 98,30% sensitive against NOR, 91,5% sensitive against OFX, 91,50% sensitive against CIP and 96,6% sensitive against AN . In contrast, the Salmonella strains sensitivity was lower in the other tested antimicrobial substances: C (32,2% sensitive strains), GM (8,5%), A (16,9%), CF (11,9%), T (3,4%), FU (1,7%) . Out of 59 strains, 45 where resistant to more than four antibiotics, the most often observed pattern was: A, CAZ, CF, GM, T, C, FU. Scand J Infect Dis, 1996, 28(5), 529 - 31 Selection of multiple resistance in Salmonella enteritidis during treatment with ciprofloxacin; Pers C et al.; We report on a strain of Salmonella enteritidis which was found to be resistant to both ciprofloxacin and beta-lactams and chloramphenicol in a patient treated with ciprofloxacin for a splenic abscess . We conclude that in invasive infections such as a splenic abscess caused by Salmonella, early surgical intervention is important . Multiple-drug-resistant strains of Salmonella may be selected by treatment with ciprofloxacin alone. J Clin Lab Anal, 1996, 10(6), 458 - 64 Importance of correlations between phagocytic activity and superoxide production of neutrophils under conditions of voluntary exercise and stress; Kuriyama T et al.; The importance of the neutrophil function to host defense and tissue damage has been widely recognized . However, the usefulness of the correlation analysis between phagocytic activity and superoxide production of neutrophils is unknown . We investigated the relationship by histochemical NBT assay using rats and mice exposed to voluntary exercises and stresses . The following conclusions were shown from the results in this report and from our previously published findings . The results of voluntary exercise showed significant positive correlations between phagocytic activity and superoxide production of neutrophils after the continuation of the exercise for 8 months, but no relationship after only 3 or 4 months . However, when Salmonella was injected into the same group after 4 months, significant positive correlations were observed immediately following and on the 6th and 14th days after injection . In contrast, negative correlations emerged after psychological stress and severe-crowding stress, suggesting that appropriate expression of neutrophil function was disturbed by the reverse effects, such as by suppression of oxygen-dependent killing capacity or over-production of toxic free radicals subsequent to these stress . These results suggest that the correlations of phagocytic activity and superoxide production of neutrophils reflect whether a neutrophil functional state is appropriate or not. Kurume Med J, 1996, 43(3), 185 - 8 An experimental animal model of primary biliary cirrhosis induced by lipopolysaccharide and pyruvate dehydrogenase; Ide T et al.; Previously, we found that the antibody titer belonging to the IgM class produced against the bacterial antigen (Lipid A) was elevated in sera from patients with primary biliary cirrhosis (PBC) . On the other hand, the targets of the mitochondrial autoantibodies have been identified as being components of the pyruvate dehydrogenase complex (PDH) . We tried to produce an experimental animal model for the investigation of the association between hepatic bile duct alteration and bacterial infection . Female C57/BL mice, aged 4 weeks, were used . An emulsion consisting of lipopolysaccharide (LPS) derived from Salmonella minnesota Re595, PDH, and Freund's adjuvant was prepared . This emulsion was subcutaneously injected on the back of the mice . The mice were divided into a control group (n = 5), a group given LPS (n = 5) alone, those given PDH alone (n = 5), and those given a combination of LPS and PDH (n = 5) . The antigens were administered once a week every week with a maximum duration of administration of 24 weeks . The serum levels of IgM after 24 weeks in the LPS and LPS + PDH groups were 2.5 times higher than those in the control and PDH groups . The light microscopic findings of liver tissue revealed that infiltration of lymphocytes and plasma cells in the portal area, proliferation of the bile duct, and degeneration of the biliary epithelial cells were more prominent in the PDH and LPS + PDH groups than in the other groups . These results indicate that our animal model may be useful in investing the pathogenesis of PBC. Environ Mol Mutagen, 1996, 28(3), 284 - 93 Structure-activity relationships in the mutagenicity and cytotoxicity of putative metabolites and related analogs of benzene derived from the valence tautomers benzene oxide and oxepin; Stark AA et al.; A series of putative metabolites and related analogs of benzene, derived from the valence tautomers benzene oxide and oxepin, was tested for mutagenicity (reversions to histidine prototrophy and forward mutations to resistance to 8-azaguanine) and for cytotoxicity by the Ames Salmonella mutagenicity test . Benzene was not mutagenic in either assay . The benzene oxide-oxepin system and benzene dihydrodiol induced point mutations but not frameshifts . 4,5-sym-Oxepin oxide, which is a putative metabolite of the oxepin valence tautomer; 3,6-diazo-cyclohexane-1,6-3,4-dioxide, a synthetic precursor of sym-oxepin oxide; and transoid-4,11-dioxatricyclo(5.1 0)undeca-1,6-diene, a stable bridge-head diene analog of sym-oxepin oxide, were toxic but not mutagenic in both assays . 4H-Pyran-4-carboxaldehyde, a stable acid catalyzed rearrangement product of sym-oxepin oxide, was not mutagenic and much less cytotoxic than sym-oxepin oxide . Stable analogs of the valence tautomer benzene oxide, namely syn-indan-3a,7a-oxide and syn-2-hydroxyindan-3a,7a-oxide, were mutagenic and induced point mutations . All compounds were cytotoxic to Salmonella . Firstly, the apparent decay times of these chemicals, especially that of sym-oxepin oxide, were surprisingly longer than expected, as judged by quantitative plate diffusion assays . Secondly, it is concluded that if benzene oxide is further metabolized in its oxepin tautomeric form, toxic but not mutagenic products are formed . Thirdly, the relatively weak mutagenicity of benzene oxide may be mainly due to its instability and corresponding low probability to reach intracellular polynucleotide targets, whereas stable analogs of benzene oxide are relatively more potent mutagens. Biochimie, 1996, 78(5), 351 - 63 Towards a unified grammatical model of sigma 70 and sigma 54 bacterial promoters; Collado-Vides J; The organization and integration of large amounts of information on the regulation of gene expression requires new conceptual frameworks to facilitate the discovery of general principles underlying different mechanisms of gene regulation . I have developed a formalism based on generative grammar to explicitly describe pertinent regulatory properties of mechanisms of regulation . The formal proof that justifies the use of generative grammar has been made . We have collected and analyzed an exhaustive database of sigma 70 and sigma 54 promoters in E coli and Salmonella where there is sufficient knowledge on the regulation of these genes . This collection has supported the construction of a grammatical model of the sigma 70 type of promoters . The purpose of this paper is to present some ideas towards the construction of a unified grammar capable of describing regulatory arrays for the sigma 70 and the sigma 54 bacterial promoters . This model is not intended to simply generate the set of binding sites of regulators distributed in a linear array in the DNA . It should also reflect the biological differences on the regulatory mechanisms of these collections, as understood from the analysis that we have done on these collections (Gralla and Collado-Vides, 1996) . Based on the biology of these two types of bacterial promoters, a hypothesis is proposed stipulating that in principle it is feasible to activate sigma 70 promoters at a distance, an exclusive property of the sigma 54 class shared with promoters of higher organisms . The model presented assumes this hypothesis is correct . The ideas presented support the beginning of a unique 'universal' grammar for the sigma 70 and sigma 54 promoters . The specification of certain parameters would derive the respective specific sigma 70 and sigma 54 grammatical models. Dev Biol Stand, 1996, 87, 277 - 81 Factors influencing the stability of live oral attenuated bacterial vaccines; Cryz SJ Jr et al.; Live oral attenuated vaccines against typhoid fever (Salmonella typhi Ty21a) and cholera (Vibrio cholerae CVD 103-HgR) have been licensed for human use . Vaccine potency is dependent upon each dose containing a minimum number of viable organisms and galenic parameters . To ensure long-term stability, such vaccines must be stored at 5 degrees C +/- 3 degrees C . However, exposure to ambient temperatures (25 degrees C) for short periods of time (< 7 days) does not compromise vaccine potency . Brief exposures (< or = 24 hours) to temperatures as high as 37 degrees C will also not render the vaccine unsuitable for use . The Ty21a vaccine is available either as enteric-coated capsules or as a "liquid formulation", while CVD 103-HgR is presented only in the latter form . Each galenic formulation presents unique challenges with regard to the production of stable vaccines . Residual moisture, excipients, and processing temperatures during manufacturing were all found to markedly affect vaccine stability. J Infect, 1996 Jan, 32(1), 27 - 32 Emergence of ciprofloxacin resistance during treatment of Salmonella osteomyelitis in three patients with sickle cell disease; Workman MR et al.; The treatment of salmonella osteomyelitis in sickle cell disease (SCD) is difficult and the emergence of antibiotic resistance in Salmonella spp presents further problems for clinicians treating SCD . Three patients presented with salmonella bacteraemia . Treatment with several intravenous antibiotics did not prevent the subsequent development of osteomyelitis . Emergence of resistance to multiple antibiotics, including ciprofloxacin, during the treatment of salmonella osteomyelitis in SCD patients is reported here for the first time . Ceftriaxone 2 g once daily given for 3 months to 3 years was an effective and convenient treatment for osteomyelitis caused by multiply-resistant salmonella . Two of these patients gave a definite history of diarrhoea, and stool cultures confirmed the presence of Salmonella spp in one . Our experience shows that salmonella osteomyelitis may not be prevented by early treatment of bacteraemia in SCD patients . Other measures to reduce the risk of salmonella infection are therefore necessary. Adv Exp Med Biol, 1996, 392, 335 - 44 Reduction of risks associated with fumonisin contamination in corn; Park DL et al.; Fumonisins, produced by Fusarium moniliforme, have been recognized as an important group of chemicals which cause health risks in domestic animals and humans . Decontamination procedures for fumonisin B1 (FB1) were evaluated to determine chemical modification and reduction in toxic/carcinogenic potentials . Ammoniation, a procedure used for decontamination of aflatoxins, yielded a 79% reduction in FB1 levels in naturally contaminated corn . Authentic FB1 and FB1-contaminated corn were exposed to alternative treatments containing various combinations of Ca(OH)2, NaHCO3, and H2O2 simulating a modified nixtamalization procedure . Treatments also included NH4Cl alone or in combination with H2O2 or horseradish peroxidase . The brine shrimp assay (Artemia spp.) was used to monitor toxicity of reaction products and the Salmonella/microsomal mutagenicity assay, using tester strains TA-100 and TA-102, was used to evaluate mutagenicity . Treatments of FB1-contaminated corn simulating modified nixtamalization (Ca(OH)2 alone or with Na-HCO3 + H2O2) gave 100% reduction of FB1 and reduced brine shrimp toxicity by ca . 40% . The positive mutagenic potential (without S-9) for extracts of corn naturally contaminated with FB1 was eliminated following exposure to modified nixtamalization . Reaction products formed when pure FB1 was treated with Ca(OH)2 and H2O2/NaHCO3 were inhibitory to Bacillus cereus, B . subtilis, and B . megaterium . No inhibitory potential was evident for contaminated corn extracts following the chemical treatments. Clin Imaging, 1996 Jan-Mar, 20(1), 26 - 30 Diagnostic imaging of Salmonella-related mycotic aneurysm of aorta by CT; Lee MH et al.; The purpose of this study was to review the computed tomography (CT) appearance of mycotic aneurysm of the aorta caused by Salmonella infection . Eight patients were suggested to have mycotic aneurysm of the aorta by clinical presentation of fever, abdominal or back pain, leukocytosis, and pulsatile abdominal mass in addition to positive blood or tissue culture of salmonella . All underwent plain radiography, abdominal sonography, and CT for confirmation . Five patients died during hospitalization despite medical or surgical treatment . CT features of mycotic aneurysm of aorta included (a) hazy aortic wall with rupture; (b) gas-forming inflammation around the aneurysm; (c) retroperitoneal paraaortic fluid collection and vertebral erosion; and (d) thrombus formation within a false lumen after aneurysmal rupture . Because of its availability and noninvasiveness, CT is the major diagnostic modality to use for Salmonella-related mycotic aneurysm. Clin Rheumatol, 1996 Jan, 15 Suppl 1, 74 - 8 Comparison of peptides eluted from the groove of HLA-B27 from Salmonella infected and non-infected cells; Ringrose JH et al.; Reactive arthritis (ReA) is associated with the MHC class-I molecule HLA-B27 and caused by certain Gram-negative bacteria . The mechanism by which HLA-B27 confers a higher susceptibility for this disease compared to other MHC Class-I alleles is still not known . We investigated whether infection of human HLA-B27+ cells is able to change the peptide repertoire presented by these HLA-B27 molecules . To this end large quantities of a B-cell line (C1R-B27) transfected with HLA-B2705 were infected with S . typhimurium . Peptides were eluted from the B27 molecules and separated by Reversed Phase Chromatography (RPC) . We then compared the peptide profiles obtained from S . typhimurium infected CIR B-cells with that obtained from non infected cells . Apart from a few additional peaks present in the profile derived from the infected batch the peptide profiles were almost identical . A few fractions were subjected to sequencing by Edman degradation . All peptides found were nonameres with arginine (Arg) at position 2 which is in agreement with the previously described HLA-B27 peptide binding motif . The majority of peaks expressed a mixture of at least four different peptides . The analysis of differences between HLA-B27 bound peptides from Salmonella infected and non infected cells might lead to the identification of T-cell epitopes shared by Salmonella and autoantigens. Environ Health Perspect, 1996 Jan, 104(1), 40 - 6 Anomalous nonidentity between Salmonella genotoxicants and rodent carcinogens: nongenotoxic carcinogens and genotoxic noncarcinogens; Yoshikawa K; According to current data, the capacity to cause nonprogrammed or unscheduled cell proliferation in target tissues, a common characteristic of chemical carcinogens, may play a more important role in the development of tumors than does genotoxicity . This paper provides strong support for the validity of this conclusion . Ames-negative nongenotoxicants may be considered to be carcinogenic primarily because of their ability to induce cell proliferation in animal tissues and organs . In addition, such nongenotoxic carcinogens may also provide latent and modest DNA (equivocal) modifications that never lead to Ames-positive events . Conversely, noncarcinogenesis by Ames-positive agents is likely to be linked to a lack of stimulation of cell division . Nongenotoxic and genotoxic carcinogens rely on both cell proliferation and equivocal DNA modification for their full carcinogenicity . Such equivocal DNA modifications do not appear to be formed by tumor promoters . The role of cell proliferation may provide a favorable milieu for the occurrence of genetic instability, give rise to selective "apoptosis-resistant abnormal cells," and then affect clonal expansion of these cells . Therefore, understanding the influence of nongenotoxic and genotoxic carcinogens on cell proliferation capability is a key point in determining the mechanisms of chemical carcinogenesis . Considering the contradictory and common features of genotoxicants and carcinogens, early detection of nonprogrammed cell proliferation is the most effective approach to predict human and rodent carcinogenicity. Kansenshogaku Zasshi, 1996 Jan, 70(1), 51 - 9 {In vitro antibacterial activity of pazufloxacin (PZFX) against clinical isolates from infectious enteritis}; Fukuyama M et al.; Antibacterial activity of pazufloxacin (PZFX) against 65 strains of Shigella spp., 13 strains of Salmonella spp., 7 strains of Escherichia coli, 4 strains of Vibrio parahaemolyticus, 4 strains of V . cholerae O1, 2 strains of Aeromonas spp., 4 strains of Plesionomas shigelloides and 3 strains of V . cholerae non-O1 isolated from patients of infectious enteritis and carriers was compared with that of ofloxacin (OFLX), ciprofloxacin (CPFX), tosufloxacin (TFLX) and nalidixic acid (NA) . The MIC90 of PZFX against Shigella spp., Salmonella spp . and E . coli were 0.025, 0.025 and 0.025 micrograms/ml, respectively . The MIC90 of PZFX against Shigella spp . was comparable to that of CPFX, 2-fold higher than that of TFLX and 4-fold lower than that of OFLX . Against Salmonella spp., MIC90 of PZFX was comparable to TFLX and 2- to 8-fold lower than those of CPFX and OFLX . PZFX showed the highest antibacterial activity between the drugs tested . Against other species, the MIC90 values of PZFX were < or = 0.006-0.1 micrograms/ml . No NA-resistant isolates were observed . The antibacterial activity of PZFX against stocked strains (clinical isolates from Aug 1989 to Feb 1991), containing 51 strains of Shigella spp., 50 strains of Salmonella spp., 19 strains of E . coli, 12 strains of V . cholerae O1 and 13 strains of V . parahaemolyticus, was also investigated . The MIC90 of PZFX of each strains were 0.05 micrograms/ml for Shigella spp., 0.05 micrograms/ml for Salmonella spp., 0.1 micrograms/ml for E . coli, 0.0125 micrograms/ml for V . cholerae O1, 0.2 micrograms/ml for V . parahaemolyticus, respectively . As shown above, PZFX has strong antibacterial activity against isolates from infectious enteritis and this suggests the usefulness of PZFX for the treatment of these patients and carriers. Kansenshogaku Zasshi, 1996 Jan, 70(1), 42 - 50 {Serovar-distribution and drug-resistance of Salmonella strains isolated from domestic and imported cases in 1990-1994 in Tokyo}; Matsushita S et al.; A total of 3,647 non-typhoidal Salmonella strains consisting of 2,655 domestic strains and 992 imported strains isolated in Tokyo from 1990 to 1994, were examined for their serovar-distribution and their drug-resistance . The serological typing results showed that the domestic strains were classified into 15 O-groups and 96 serovars, and the imported strains were classified into 13 O-groups and 73 serovars . Among the serovars identified, Salmonella serovar Enteritidis (S . Enteritidis), S . Thompson, S . Hadar, S . Litchfield, and S . Tennessee were predominant in the domestic strains, whereas S . Hadar, S . Enteritidis, S . Anatum, S . Derby, and S . Blockley were predominant in the imported strains . The drug-resistance test using 9 drugs (CP, TC, SM, KM, ABPC, ST, NA, FOM, and NFLX) showed that 30.5% of the domestic strains and 40.5% of the imported strains were resistant to any of the drugs examined . The serovars of a high resistant rate during this period were S . Hadar (96.2%), S . Blockley (88.7%), S . Enteritidis (63.4%), S . Virchow (54.3%), and S . Typhimurium (51.3%) in the domestic strains and S . Krefeld (100%), S . Hadar (98.9%), S . Blockley (98.2%), S . Emek (83.3%), S . Kentucky (76.5%), S . Panama (69.2%), S . Derby (63.8%), S . Typhimurium (57.1%), S . Rissen (55.6%), and S . Agona (53.7%) in the imported strains . Drug-resistance patterns of the resistant isolates varied to 62 types . Prevalent patterns recognized were SM, TC.SM, TC.SM.KM, TC, TC.SM.KM.ABPC and CP.TC.SM.KM in the domestic strains and TC.SM, TC, CP.TC.SM.ST, TC.SM.KM, and CP.TC.SM.KM in the imported strains. Kansenshogaku Zasshi, 1996 Jan, 70(1), 29 - 41 {Bacteriological studies of travellar's diarrhoea . 5) Analysis of enteropathogenic bacteria at Osaka Airport Quarantine Station from January 1992 through September 3rd, 1994}; Ueda Y et al.; During the last 2 years and 8 months before the closure of Osaka Airport Quarantine Station (from Jan . 1992 to Sep . 3, 1994), a total of 7,421,909 overseas travellers were quarantined . 15,919 reported themselves of suffering from diarrhoea . Bacteriological examination of a total of 6,031 individuals' stools were performed . 1) Various enteropathogenic bacteria were isolated from 31.2% of the stools examined . Isolated species were as follows: Plesiomonas shigelloides, 1,127 cases (59.9%); Vibrio parahaemolyticus, 293 cases (15.6%); Salmonella spp., 262 cases (13.9%); Shigella spp., 235 cases (12.5%); Aeromonas sobria, 93 cases (4.9%); V . cholerae non-O1, 69 cases (3.7%) . 2) The enteropathogenic bacteria were isolated through out the year without any seasonal variation . 3) The major regions where the travellers were infected with the pathogens are as follows: V . cholerae non-O1 (NAG Vibrio) and enteropathogenic Escherichia coli, South-East and South-West Asia; Vibrio other than NAG, South-East and East Asia; Shigella, widely distributed but especially in India; P . shigelloides and Salmonella, widely distributed . 4) 2 strains of toxigenic (cholera toxin-producing) V . cholerae O139 were isolated from patients who had visited Indonesia and Thailand, respectively . 5) In 320 cases (17%), plural enteropathogenic bacteria were isolated from single patients, suggesting a high frequency of the mixed infections . 6) Among Shigella strains, S . sonnei were isolated the most, followed by S . flexneri (24.7%), S . boydii (8.8%) and S . dysenteriae (2.9%) . 7) Among Salmonella serovers, Salmonella Enteritidis was isolated the most frequently (39 cases, 14.1%) . 8) 218 (91.6%) of 238 Shigella strains and 103 (37.6%) of 276 Salmonella strains were resistant to one or more drugs tested (SM.CP.TC.KM.ABPC.NA.OFLX) . 9) All of the 22 V . cholerae O1 strains were Ogawa, E1 Tor . Among them, 19 were toxigenic strains and 3 were non-toxigenic . 10) O4:K8 was the most frequently isolated serover of V . paraemolyticus . 87.4% of all V . parahaemolyticus strains were positive with thermostable direct hemolysin (TDH) gene, and 12.6% of them were positive with TDH-related hemolysin (TRH) gene by DNA-probe methods. Mol Microbiol, 1996 Jan, 19(1), 37 - 52 The identification, cloning and mutagenesis of a genetic locus required for lipopolysaccharide biosynthesis in Bordetella pertussis; Allen A et al.; Bordetella pertussis lipopolysaccharide (LPS) is biologically active, being both toxic and immunogenic . Using transposon mutagenesis we have identified a genetic locus required for the biosynthesis of LPS in B . pertussis, which has been cloned and sequenced . We have also identified equivalent loci in Bordetella bronchiseptica and Bordetella parapertussis and cloned part of it from B . parapertussis . The amino acid sequences derived from most of the genes present in the sequenced B . pertussis locus are similar to proteins required for the biosynthesis of LPS and other complex polysaccharides from a variety of bacteria . The genes are in a unique arrangement in the locus . Several of the genes identified are similar to genes previously shown to play specific roles in LPS O-antigen biosynthesis . In particular, the amino acid sequence derived from one of the genes is similar to the enzyme encoded by rfbP from Salmonella enterica, which catalyses the transfer of galactose to the undecaprenol phosphate antigen carrier lipid as the first step in building oligosaccharide O-antigen units, which are subsequently assembled to form polymerized O-antigen structures . Defined mutation of this gene in the B . pertussis chromosome results in the inability to express band A LPS, possibly suggesting that the trisaccharide comprising band A is a single O-antigen-like structure and that B . pertussis LPS is similar to semi-rough LPS seen in some mutants of enteric bacteria. Vaccine, 1996 Jan, 14(1), 85 - 92 Synthetic recombinant influenza vaccine induces efficient long-term immunity and cross-strain protection; Levi R et al.; Synthetic vaccines utilize specific antigenic epitopes in order to elicit a protective immune response . In this work we examined the immunogenicity of chimeric proteins expressing influenza epitopes and their ability, as single products or in various combinations, to protect mice from viral challenge . Oligonucleotides coding for three epitopes (HA91-108, NP55-69 and NP147-158) stimulating B cells, T helper cells and cytotoxic T lymphocytes (CTLs), respectively, were individually inserted into the flagellin gene of a Salmonella vaccine strain . Immunization of mice with the resultant hybrid flagella resulted in a specific humoral or cellular response . The protective efficacy of the chimeric flagella was evaluated by intranasal immunization of mice, without any adjuvant, and subsequent challenge with infectious virus . The construct containing the B-cell epitope by itself led to partial protection . However, the addition of the two T-cell epitopes augmented the protection in a significant manner . The protective immunity conferred by this combined vaccine, comprising the three epitopes, persisted for at least 7 months after the last boost, and was effective against several influenza A strains . Furthermore, this vaccine fully protected mice from a lethal challenge, and enhanced their recovery process . Our results indicate that stimulation of the different arms of the immune system is required for effective anti-influenza response, and demonstrate the applicability of such synthetic recombinant approach for preparing a broad spectrum influenza vaccine. Vaccine, 1996 Jan, 14(1), 70 - 76 Immunopharmacological activities of the nontoxic monophosphoryl lipid A of Porphyromonas gingivalis; Ogawa T et al.; The low endotoxic lipid A derived from Porphyromonas gingivalis 381, 1-phospho beta(1-6)-linked glucosamine disaccharide with 3-hydroxy-15-methylhexadecanoyl and 3-hexadecanoyloxy-15-methylhexadecanoyl groups at the 2- and 2'-positions, respectively, induced mitogenic responses in LPS low responder C3H/HeJ as well as LPS responder C3H/HeN mouse splenocytes . The mitogenic activities of P . gingivalis lipid A in splenocytes of LPS responder mice were comparable to that of the synthetic Escherichia coli-type lipid A (compound 506) . The addition of polymyxin B resulted in the inhibition of mitogenic activity . P . gingivalis lipid A also stimulated strongly nonspecific host resistance against Pseudomonas aeruginosa infection in BALB/c mice, and specific immune response in guinea pigs against infection with P . gingivalis . Furthermore, P . gingivalis lipid A demonstrated antitumour activity against MH134 hepatoma in C3H/HeN mice . These life-preserving with tumour regression properties were comparable to those of monophosphoryl lipid A derived from Salmonella minnesota Re 595 . Thus, P . gingivalis lipid A appears to have beneficial properties as an immunopharmacological agent. Shock, 1996 Jan, 5(1), 41 - 6 Activation of thromboxane A2 receptors alters lipopolysaccharide-induced adherence of THP-1 cells; Wagner RS et al.; U46619, a thromboxane A2 (TXA2) mimetic, inhibits human monocyte chemotactic responses, suggesting that TXA2, an arachidonic acid metabolite, may alter monocyte adhesion . We tested the hypothesis that TXA2 alters Lipopolysaccharide (LPS)-induced adhesion of THP-1 cells, a human monocytic leukemia cell line . Salmonella enteritidis endotoxin (1 microgram/mL) induced a significant (p < .05; n = 6) increase in the adherence of THP-1 cells (basal, 5.7 +/- 1.8 micrograms/well; LPS, 78.8 +/- 4.9 micrograms/well) . Treatment of THP-1 cells with indomethacin or TXA2 receptor antagonists before LPS stimulation significantly (p < .05) enhanced adhesion, suggesting that endogenously produced TXA2 or prostaglandins alter LPS-induced THP-1 cell adhesion . TXA2 mimetics significantly decreased (p < .05; n = 5 and n = 3, respectively) LPS-induced THP-1 cell adhesion . This effect was blocked by three structurally dissimilar TXA2 receptor antagonists . These results support the hypothesis that TXA2 alters LPS-induced adhesion of THP-1 cells. Zh Mikrobiol Epidemiol Immunobiol, 1996 Jan-Feb, (1), 78 - 80 {The nosoparasitic form of salmonellosis}; Brodov LE et al.; The nosoparasitic form of salmonellosis occurs not only in cases of the association of salmonellosis with infectious diseases, but also in noninfectious patients, mostly in oncological and hematological cases . The appearance of the nosoparasitic form of salmonellosis was observed in 9 patients; of these, 5 with leukosis, 2 with malignant tumors, 1 with erythremia and 1 with cytostatic disease . Concomitant Salmonella infection contributed to the aggravation of the main disease . In 6 out of 9 cases patients with the nosoparasitic form of salmonellosis remained in oncological and hematological hospitals, and no cases of hospital infection were registered . Immunodeficiency played an important role in the development of the nosoparasitic form of salmonellosis in these patients. Scand J Infect Dis, 1996, 28(2), 177 - 80 Norfloxacin and Salmonella excretion in acute gastroenteritis--a 6-month follow-up study; Pitkajarvi T et al.; In a controlled, randomized, double-blind study, 100 patients (66 women, 34 men; age 18-69 years) with acute salmonellosis were treated with norfloxacin (400 mg) or placebo tablets twice daily for 10 days to compare the effects on the excretion time of salmonella bacteria . In all patients salmonellae were detected in the stools before the start of treatment . The follow-up included 6 stool cultures after the start of treatment: day 3-4, day 12-14, and 4 times during 1-6 months . At 3-4 days there were 98% non-excretors in the norfloxacin group (46/47 patients) compared to 38% (17/45) in the placebo group (p < 0.001) . The cumulative 6-month elimination rate in norfloxacin patients at 3-4 days was 72%, which was significantly (p = 0.0001) greater than the 31% in the placebo patients . However, there was no significant difference in the proportion of non-excretors or the elimination rate between the 2 groups at the following visits . Only one patient had an adverse event resulting in discontinuation of the treatment . We conclude that norfloxacin treatment for 10 days decreased the excretion of salmonella bacteria during the first week, but there was no difference in excretion rates 1-6 months after treatment initiation in the treatment versus placebo group. Scand J Infect Dis, 1996, 28(2), 171 - 5 Salmonella infections: a retrospective 10-year analysis of 134 cases in a regional hospital in Taiwan; Yang CH et al.; A total of 134 cases of salmonella infections have been noted during the past 10 years in our hospital . Cases of non-typhoidal salmonellosis increased gradually but infections due to Salmonella typhi did not show the same trend . Gastroenteritis was the most prevalent diagnosis in patients below 1 year of age and non-typhoidal bacteraemia and localized infections were the most prevalent in patients over 50 years . Diabetes mellitus was an important underlying disease especially in patients with localized infections (86%) . Travelling history played an important role in cases of enteric fever . The susceptibility pattern in non-typhoidal salmonella changed markedly over the study period; multiple drug resistance was noted . The susceptibility pattern of S . typhi showed no significant change . Seven deaths due to salmonella infections were noted (5.2%); all due to non-typhoidal salmonellosis, especially serogroup B . Age above 50 years, localized infection, infection with serogroup B and diabetes were poor prognostic factors. Antimicrob Agents Chemother, 1996 Jan, 40(1), 115 - 21 Antibacterial activity of a synthetic peptide (PR-26) derived from PR-39, a proline-arginine-rich neutrophil antimicrobial peptide; Shi J et al.; PR-39 is a proline-arginine-rich (PR) neutrophil antibacterial peptide originally identified and purified from the porcine small intestine . We report on the synthesis of a functional antibacterial domain of PR-39, the first 26 amino acid residues of the NH2 terminus . PR-26 was as potent as or more potent than PR-39 against enteric gram-negative bacteria . This truncated form of PR-39 potentiated neutrophil phagocytosis of Salmonella choleraesuis and decreased the level of S . typhimurium invasion into intestinal epithelial cells . Scanning electron microscopy confirmed that these peptides did not lyse cells by pore-forming mechanisms; however, they potentiated the antibacterial capabilities of a pore-forming peptide, magainin A . In addition, PR-26 was not toxic to epithelial cells at concentrations several times greater than its bactericidal concentration . These data suggest that PR-39 and its functional domain, PR-26, may potentiate the host's defense capabilities against gram-negative infections. Biophys J, 1996 Jan, 70(1), 321 - 9 Planar asymmetric lipid bilayers of glycosphingolipid or lipopolysaccharide on one side and phospholipids on the other: membrane potential, porin function, and complement activation; Wiese A et al.; We have determined some physicochemical properties of the monosaccharide-type fraction (GSL-1) of glycosphingolipids, the major glycolipid components of the outer leaflet of the Gram-negative species Sphingomonas paucimobilis . These properties included the state of order of the hydrocarbon moiety, the effective molecular area, surface charge density, and intrinsic transmembrane potential profile of reconstituted planar asymmetric GSL-1/phospholipid bilayer membranes . We have, furthermore, investigated the insertion into and the function of porin channels in the reconstituted bilayers and the complement-activating capability of GSL-1 surfaces . All results were compared with respective data for deep rough mutant lipopolysaccharide of Salmonella minnesota R595 . We found a remarkable agreement in most functional properties of the two glycolipids. Acta Vet Scand, 1996, 37(2), 203 - 11 Acute post-treatment enterocolitis in 13 horses treated in a Norwegian surgical ward; Larsen J et al.; Case histories, results of laboratory analyses, treatment regimens and outcome are described for 13 horses that developed acute enterocolitis after various surgical treatments . Twelve of the 13 horses had been cast in lateral recumbency, and 10 of those 12 had received general anesthesia . Eleven horses had been treated with antimicrobial drugs . Most horses (11) developed diarrhea 2 days after initiation of treatment, with a variation from 1 to 5 days . The most apparent symptoms were fever, up to 40.5 degrees C, elevated heart rate, discoloration of mucous membranes, and diarrhea . Dehydration, acidosis and leukopenia were marked at the time clinical signs occurred . Packed cell volume and total serum protein values were elevated . Therapy was directed toward replacement of fluid losses, restoration of acid-base balance, and counteraction of inflammation . Seven horses (54%) died or were euthanized . At necropsy, pathological changes showed large variations between individuals . Salmonella spp . were not isolated from any of the horses, and no common causative agent was identified . Preventive efforts to avoid post-treatment enterocolitis have been taken with regard to preoperative routines, premedication and anesthesia, with apparent success. Acta Clin Belg, 1996, 51(3), 175 - 83 Lung abscess due to nontyphoid Salmonella in an immunocompromised host . Case report with review of the literature; Ridha AG et al.; Lung abscess due to nontyphoid Salmonella (NTS) with or without other intestinal or extra-intestinal involvement is very rare . A literature review (Medline search) revealed only 20 cases including ours with this extra-intestinal manifestation of Salmonella infection . The case of a 49-year-old, HIV-positive man from Zaire is reported . Diagnosis was established by direct transthoracal CT-guided puncture of the abscess, a hitherto not reported procedure in this setting . Treatment with oral ciprofloxacin resulted in clinical and radiographic improvement . Underlying immunodeficiency seems to play an important role, but the real pathophysiological mechanisms remain unsolved . It is particularly seen in HIV-positive patients with impaired cellular immunity since Salmonella is an intracellular pathogen whose eradication involves natural killer cells and antibody-induced cellular cytotoxicity . A possible explanation is that NT-Salmonella bacteraemia is much more frequent in AIDS-patients as compared to the general population . Salmonella bacteraemia can then spread to other tissues and organs such as the lungs, but why only the lungs are involved in some cases remains unclear . The characteristics of Salmonella lung abscess is discussed and the literature reviewed. Free Radic Biol Med, 1996, 20(2), 189 - 97 Neutrophil-induced lung damage after hepatic ischemia and endotoxemia; McGuire GM et al.; Administration of Salmonella enteritidis endotoxin (0.5 mg ET/kg) during reperfusion (RP) after short-term hepatic ischemia (20 min) caused severe liver injury induced by Kupffer cells and neutrophils and a high mortality rate . To investigate potential lung damage in this model, lung wet-to-dry weight ratios (W/D) and broncho-alveolar lavage (BAL) protein content were determined after 4 h of reperfusion . Both parameters increased significantly during RP/ET (W/D: 4.4 +/- 0.1; BAL: 639 +/- 30 micrograms/ml) compared to controls (W/D: 3.5 +/- 0.1; BAL: 332 +/- 17) . The antioxidants Trolox or tirilazad mesylate (U-74006F) effectively reduced the BAL protein increase . Alveolar macrophages were not activated; however, neutrophils isolated from the lung microvasculature of RP/ET animals showed a 300% increase of spontaneous and PMA-induced superoxide formation compared to controls (spontaneous: 1.4 +/- 0.5 nmol O2-/h/10(6) cells; PMA: 2.2 +/- 0.4) . Complement factors and TNF-alpha injection induced a similar priming of vascular neutrophils for superoxide generation . Vascular neutrophil activation highly correlated with the severity of lung injury . It is concluded that neutrophils accumulated in the lung microvasculature were the major source of the oxidant stress and mainly responsible for lung injury under these conditions . Antioxidants such as tirilazad mesylate (U-74006F) may have therapeutic potential for attenuating lung injury induced by remote organ trauma and a systemic inflammatory response. Ital J Gastroenterol, 1996 Jan, 28(1), 31 - 3 Hepatic abscess caused by Salmonella typhi: diagnosis and management by percutaneous echo-guided needle aspiration; Giorgio A et al.; Three cases of liver abscesses due to Salmonella typhi (2 solitary, 1 with double localization in the right lobe) are described in which specific diagnosis was based on percutaneous echo-guided aspiration of the lesions . Haemocultures and coprocultures were negative, in all cases, and pus-cultures of aspirated material from cavities grew Salmonella typhi; Widal became significantly positive only in one patient 15 days after discharge . Percutaneous needle drainage, combined with chloramphenicol therapy, was successfully performed under echo guidance; only in one case was a second aspiration needed three days after the first one . Fever disappeared within 48-72 hours after drainage of the abscess . No complications or side-effects were observed. Pept Res, 1996 Jan-Feb, 9(1), 21 - 7 Interaction with DNA of oligopeptides related to the Arc repressor; Helbecque N et al.; Three different peptides, A13, A14x2 and A20, related to the Arc repressor from Salmonella phage P22, were synthesized . They all contained the 13 N-terminal residues of Arc known to form a beta-sheet interacting with the operator OArc . In the case of A20, the tripeptide Lys-Trp-Lys was added in the C-terminal position because of its propensity to increase affinity to DNA . The interaction of the three peptides with OArc and with other related (OMnt from the same phage) and unrelated oligonucleotides was followed using circular dichroism, filter binding assays and DNaseI protection experiments . While Kd = 10(-9) M for the protein, 8.7 x 10(-5) M and 7.7 x 10(-6) M Kd values were obtained for A14x2 and A20 interacting with OArc. Annu Rev Immunol, 1996, 14, 533 - 61 Salmonellosis: host immune responses and bacterial virulence determinants; Jones BD et al.; The lifestyle of bacterial pathogens requires them to establish infection in the face of host immunity . Upon entering a potential host, a variety of interactions are initiated, the outcome of which depends upon a myriad of attributes of each of the participants . In this review we discuss the interactions that occur between pathogenic Salmonella species and the host immune systems, but when appropriate to broaden perspective, we have provided a general overview of the interactions between bacterial pathogens and animal hosts . Pathogenic Salmonella species possess an array of invasion genes that produce proteins secreted by a specialized type III secretion apparatus . These proteins are used by the bacteria to penetrate the intestinal mucosa by invading and destroying specialized epithelial M cells of the Peyer's patches . This maneuver deposits the bacteria directly within the confines of the reticuloendothelial system . The host responds to these actions with nonspecific phagocytic cells and an imflammatory response as well as by activating specific cellular and humoral immune responses . Salmonella responds to this show of force directly . It appears that the bacteria invade and establish a niche within the very cells that have been sent to destroy them . Efforts are underway to characterize the factors that allow these intracellular bacteria to customize intracellular vacuoles for their own purposes . It is the constant play between these interactions that determines the outcome of the host infection, and clearly they will also shape the evolution of new survival strategies for both the bacterium and the host. Enferm Infecc Microbiol Clin, 1996 Jan, 14(1), 31 - 3 {Detection of resistance to the amoxicillin-clavulamic acid combination in Salmonella and Shigella}; Miro E et al.; PURPOSE: To study the emergence of amoxicilline/clavulanate resistance in Salmonella and Shigella . MATERIAL AND METHODS: We have studied 118 strains of Salmonella enterica and 11 strains of Shigella flexneri isolated in our laboratory along 1993 . The MICs values for amoxicilline/clavulanate were determined by the E-Test method and confirmed by the standard agar dilution method . RESULTS: We have observed that 6% (7 out of 118 strains) of Salmonella enterica and 42% (5 out of 11 strains) of Shigella flexneri isolates exhibited an intermediate susceptibility or were resistant to amoxicilline/clavulanate with MICs values ranging between 16 mg/l and 32 mg/l . CONCLUSIONS: Along 1993 we have detected the emergence of an amoxicilline/clavulanate resistance in salmonellae and shigellae strains . To our knowledge this fact has not been published up to now (Medline, 1990-October 1994) . We don't know the clinical importance of this fact. Natl Med J India, 1996 Jan-Feb, 9(1), 25 - 7 Spinal tuberculosis with neurological deficits; Vidyasagar C et al.; Two hundred patients suffering from tuberculosis (TB) of the spine with neurological complications were the subjects of this review . They were graded according to the Frankel system into--A: complete neurological deficit; B: sparing of some sensation; C: sparing of sensation but no useful motor function; D: sparing of sensation and useful motor function; and E: no deficits . Investigations carried out included detailed neurological assessment, radiography, contrast myelography and, in the later stages of the study, spinal computerized tomography (CT) scan . The authors believe that contrast myelography provides the best indication of spinal compression in TB spine . Treatment was by surgical decompression followed by chemotherapy . The surgical approach for thoracic spine disease was by the anterior transthoracic route . Cervical lesions were also approached by the anterior route, lateral to the carotid vessels . Unexpected findings during operation included lymphoma, plasmacytoma, non-tuberculous granulation tissue, salmonella osteomyelitis and tumour metastasis . Ten patients died during the postoperative period, all of whom had extensive systemic TB . When indicated, antituberculous drugs were administered postoperatively for two years and immobilization was done in a plaster cast for 3 months . Only 30 patients showed partial recovery . Improvement was found to be related to the grade of deficit; thoracic lesions with severe neurological deficits showed the least improvement while lumbar disease had the best outcome . The study recommended a combination of surgery and chemotherapy for all cases of TB spine with neurological deficits after a short delay during which respiratory function should be improved . The surgery should aim at decompression of the cord by removal of pus, granulation tissue and sequestra, with internal splintage with bone grafts to reduce the hospital stay . Conservative treatment is unwise because it is not always possible to distinguish between TB and neoplastic lesions. Avian Dis, 1996 Jan-Mar, 40(1), 72 - 7 Heat destruction of Salmonella in poultry feed: effect of time, temperature, and moisture; Himathongkham S et al.; Salmonella enteriditis in poultry feed declines with increasing time of exposure to heat . The interactions of temperature, time, and moisture and their effect on the thermal death of S . enteriditis were established in a factorial randomized experiment . Two other serotypes were tested, and though there was some variation, the thermal death rate followed the same basic pattern . A number of samples of poultry feed were collected and dried . After drying, the water was added back to give specific percentages of moisture contents . The feed was then inoculated with salmonella and heated at specific temperatures, with samples being removed at certain time intervals . These samples were then cultured, and the surviving salmonella were counted . A linear relationship was obtained when the logarithm of survivors was plotted against the logarithm of exposure time . These results permitted the construction of a graph depicting that the rate of reduction in numbers of S . enteriditis when plotted against increasing temperatures is linear . This linear relationship is apparent for other salmonella serotypes such as S . typhimurium and S . haardt . Our results show that the thermal death rate of salmonella in poultry feed can now be predicted at varying time, temperature, and moisture contents. Avian Dis, 1996 Jan-Mar, 40(1), 186 - 92 Efficacy of Salmonella enteritidis (SE)-immune lymphokines from chickens and turkeys on SE liver invasion in one-day-old chicks and turkey poults; Ziprin RL et al.; We have shown previously that increased resistance to Salmonella enteritidis (SE) organ infectivity in 1-day-old chicks was conferred by the immunoprophylactic administration of SE-immune lymphokines (SEILK) . These lymphokines have been found to be present in the cell culture media of concanavalin A-stimulated splenic lymphocytes obtained from SE-immunized chickens . In the present study we evaluated whether turkeys also produced SEILK and whether these lymphokines could protect 1-day-old chicks and turkey poults against SE liver invasion . In addition, we tested the ability of our original chicken SEILK to reduce SE liver invasion in turkey poults . Day-of-hatch chicks and turkey poults were injected intraperitoneally with immune lymphokines of either chicken or turkey origin . One hour later the birds were challenged per os with SE, and 20 hours later their livers were examined by bacteriological methods for the presence of SE . We found that SEILK induced from the splenic lymphocytes of SE-immunized turkeys reduced SE liver invasion in both chicks and turkey poults . Conversely, we also determined that SEILK produced by chicken splenic lymphocytes conferred protection against invasion by SE in turkey poults . This research is the first report of the production of SEILK in turkeys and also the first report on the cross-species activity of these effector molecules in chickens and turkeys. Vet Microbiol, 1996 Jan, 48(1-2), 87 - 100 Characterization of transmissible gastroenteritis coronavirus S protein expression products in avirulent S . typhimurium delta cya delta crp: persistence, stability and immune response in swine; Smerdou C et al.; The spike protein from transmissible gastroenteritis virus (TGEV) was expressed in attenuated S . typhimurium delta cya delta crp delta asd chi 3987 . Three partially overlapping fragments of TGEV S gene, encoding the amino-terminal, intermediate, and carboxy-terminal end of the protein, as well as the full length gene were inserted into the asd+ plasmid pYA292 to generate recombinant plasmids pYATS-1, pYATS-2, pYATS-3, and pYATS-4, respectively, which were transformed into S . typhimurium chi 3987 . Recombinant S . typhimurium chi 3987 (pYATS-1) and chi 3987 (pYATS-4) expressing constitutively a 53 kDa amino-terminal fragment of the S protein and the full length protein (144 kDa), respectively, showed high stability . After 50 generations in vitro 60% and 20% of the bacteria transformed with pYATS-1 and pYATS-4, respectively, expressed the S-protein antigen . Since S . typhimurium chi 3987 (pYATS-1) showed a better level of expression and stability in vitro, this recombinant strain was selected as a potential bivalent vector to induce both immunity to Salmonella and TGEV in swine . In order to study colonization of swine tissues by S . typhimurium delta cya delta crp, a gene conferring resistance to rifampicin was cloned into the chromosome of S . typhimurium chi 3987, generating chi 4509 strain . Both S . typhimurium chi 4509 (pYA292) and chi 4509 (pYATS-1) colonized the ileum of orally inoculated swine with clearance of bacteria between days 10-20 post-infection . The expression of the amino-terminal fragment of the S protein diminished the ability of S . typhimurium chi 4509 (pYATS-1) to colonize deep tissues . The recombinant strain S . typhimurium chi 3987 (pYATS-1) induced TGEV specific antibodies in both serum and saliva of orally inoculated swine. J Appl Bacteriol, 1996 Jan, 80(1), 31 - 6 Serum survival and plasmid possession by strains of Salmonella enteritidis, Salm . typhimurium and Salm . virchow; Chart H et al.; Strains of Salmonella enteritidis, Salm . typhimurium and Salm . virchow, carrying different numbers of plasmids, were examined for the ability to multiply in sera . Viable counts were performed to monitor the kinetics of growth of bacteria when in human, chicken and turkey sera . The presence of plasmids in Salm . enteritidis, Salm . typhimurium and Salm . virchow reduced considerably the ability of strains of these serotypes to multiply in serum . SDS-PAGE was used to show that growth of Salm . enteritidis in serum did not involve changes in outer membrane proteins or lipopolysaccharide . It was concluded that the carriage of plasmids may be disadvantageous for the survival in serum of certain common salmonella serotypes. Environ Mol Mutagen, 1996, 28(1), 31 - 50 A computerized connectivity approach for analyzing the structural basis of mutagenicity in Salmonella and its relationship with rodent carcinogenicity; Perrotta A et al.; We have applied a new software program, based on graph theory and developed by our group, to predict mutagenicity in Salmonella . The software analyzes, as information in input, the structural formula and the biological activities of a relatively large database of chemicals to generate any possible molecular fragment with size ranging from two to ten nonhydrogen atoms, and detects (as predictors of biological activity) those fragments statistically associated with the biological property investigated . Our previous work used the program to predict carcinogenicity in small rodents . In the current work we applied a modified version of the program, which bases its predictions solely on the most important fragment present in a given molecule, considering as practically negligible the effects of additional less important fragments . For Salmonella mutagenicity we used a database of 551 compounds, and the program achieved a level of predictivity (73.9%) comparable to that obtained by other authors using the Computer Automated Structure Evaluation (CASE) program . We evaluated the relative contributions of biophores and biophobes to overall predictivity: biophores tended to be more important than biophobes, and chemicals containing both biophores and biophobes were more difficult to predict . Many of the molecular fragments identified by the program as being strongly associated with mutagenic activity were similar to the structural alerts identified by the human experts Ashby and Tennant . Our results tend to confirm that structural alerts useful to predict Salmonella mutagenicity are generally not very strong predictors of rodent carcinogenicity . Although the predictivity level achieved for oncogenic activity improved when the program was directly trained with carcinogenicity data, carcinogenicity as a biological endpoint was still more difficult to predict than Salmonella mutagenicity. Pediatr Med Chir, 1996 Jan-Feb, 18(1), 67 - 9 {Oral rehydration in infants with acute diarrhea: using a new preparation of reduced osmolarity}; Lentidoro I et al.; Oral rehydration solutions (ORS) are widely employed in the treatment of acute diarrhea in children . Although several studies in the recent literature prove the efficacy and safety of newly formulated, reduced-osmolarity solutions, and a specific working group of the European Society for Pediatric Gastroenterology and Nutrition (ESPGAN) has made similar recommendations, such evidence in our Country is lacking . To this aim, we enrolled 38 children (age from 3 to 24 months, average: 8.2) with acute diarrhea lasting from no more than 5 days (average: 2.5) . At observation, dehydration was found to be: absent in 12 (31.6%), mild in 19 (50%), moderate in 5 (13.2%), severe in 2 (5.2%) . The last 2 patients were admitted and treated i.v., thus excluded from the study . In the 36 remaining children, a pathogen was identified in 25 (69.4%): Rotavirus in 18, Salmonella in 4, EPEC in 2, Cryptosporidium in 1 . Stool Clinitest was positive in 7/31 children, all with Rotavirus infection . All the patients received ad libitum for the first 4-6 hours exclusively a reduced-osmolarity ORS formulated according to the ESPGAN criteria . Afterwards, they were fully re-fed and were also given the same ORS until diarrhea stopped . Most of the children accepted the ORS; those who refused it were either not dehydrated and/or older than 15 months . Thirty-three out of 36 children were fully rehydrated after 12 hours, without any side effects . We conclude that such an ORS is safe and effective in the treatment of children with acute diarrhea in our settings. Hepatogastroenterology, 1996 Jan-Feb, 43(7), 121 - 6 Aminoterminal propeptide of type III procollagen: a marker of hepatic fibrosis after bile duct obstruction in the monkey; Ruf G et al.; BACKGROUND/AIMS: In an experimental study in monkeys, liver fibrosis development after segmental bile duct obstruction was investigated and correlated with the aminoterminal propeptide of type III procollagen (PIIINP) . MATERIALS AND METHODS: Segmental bile duct obstruction was produced by ligation and section of the left hepatic bile duct in all monkeys . Fibrosis induction was examined by intravenous leukotriene C4 (LTC4, 5 nmol/kg) application, endogenous LT-production stimulated by endotoxin (LPS,salmonella abortus equi, 50 ng/kg), fibrosis inhibition by dexamethasone (1 mg/kg) intramuscularly and subsequent endogenous LT-production stimulation by LPS (50 ng/kg) . Ligated and unligated liver lobe biopsies were taken 3, 7 and 12 weeks after ligation . All portal areas were measured morphometrically . PIIINP was measured by a specific radioimmunoassay each week and correlated with the morphometric results . RESULTS: Bile duct obstruction leads to secondary sclerosing cholangitis with bile duct vanishing and subsequent biliary cirrhosis combined with perivenous sclerosis and cavernous transformation of the terminal vein . The collagen concentration increased in the nonligated lobe from mean +/-SEM 1.05 +/- 0.03% to 1.53 +/- 0.19% only after LTC4 and with no difference in the other groups . In the ligated lobe collagen concentration increased significantly in all groups continuously from 1.05 +/- 0.03% up to: controls 6.1 +/- 0.9%, dexamethasone 5.9 +/- 0.8%, LPS 8.2 +/- 0.8%, LTC4 9.075 +/- 1.4% . PIIINP concentration rose within 6 weeks in the controls with hepatic bile duct obstruction from 34.43 +/- 15 ng/ml up to 57 +/- 13.27 ng/ml, after dexamethasone to 48.5 +/- 18.23 ng/ml, after LPS to 57 +/- 13.27 ng/ml, after LTC4 to 80.25 +/- 16.04 ng/ml . After 12 weeks, PIIINP decreased in the controls resp . after dexamethasone to 41.25 +/- 6.94 ng/ml resp . 33.5 +/- 7.72 ng/ml and increased after LPS resp . LTC4 up to 64.25 +/- 17.07 ng/ml resp.104 +/- 22.46 ng/ ml . The correlation of collagen deposition and PIIINP was in the controls r = 0.83, after dexamethasone r = 0.71, after LPS r = 0.83 after LTC4 r = 0.91 . CONCLUSION: PIIINP determination after segmental bile duct obstruction correlates with collagen deposition and allows evaluation of hepatic fibrosis activity. An Med Interna, 1996 Jan, 13(1), 27 - 30 {Septic arthritis caused by Salmonella enteritidis in systemic lupus erythematosus}; Gomez Rodriguez N et al.; Systemic Lupus Erythematosus (SLE) is among the chronic diseases thought to predispose patients to severe Salmonella infections . However, arthritis and osteomyelitis due to this microorganisms are more frequently seen in patients with sickle-cell disease than SLE . We report two cases of SLE and osteoarticular infections by Salmonella enteritidis: A 36-years old woman with bilateral knee arthritis associated with femoral osteomyelitis and a 22-years-old woman who presented with left knee arthritis. Rocz Akad Med Bialymst, 1996, 41(1), 90 - 5 Cross-reactivity between Borrelia burgdorferi and "arthrogenic" bacteria in sera from patients with reactive arthritis; Sobieszczanska B et al.; The occurrence of specific antibodies for "arthrogenic bacteria" and Borrelia burgdorferi was analysed in sera samples from 30 patients with reactive arthritis . The control group consisted of 30 healthy blood donors . Our data showed that 66.6% (20) of the 30 examined patients had positive tests for Borrelia burgdorferi antigens and of all the patients, most of them (85%) had increased antibody levels against Salmonella antigens, 30% had increased levels of antibodies against Shigella antigens and 10% had antibodies for Yersinia antigens . Our findings indicated that the presence of antibodies to Borrelia burgdorferi and "arthrogenic enteric bacteria" in sera samples of patients with REA is evidence of wide cross-reactivity between these microorganisms. Environ Mol Mutagen, 1996, 27(4), 306 - 13 Breakthrough of ultraviolet light from various brands of fluorescent lamps: lethal effects on DNA repair-defective bacteria; Hartman PE et al.; In a comparative study of 17 pairs of 15 W fluorescent lamps intended for use in homes and purchased in local stores, we detect over 10-fold differences in UVB + UVC emissions between various lamps . This breakthrough of ultraviolet (UV) light is in part correlated with ability of lamps to kill DNA repair-defective recA-uvrB- Salmonella . Relative proficiency of lamps in eliciting photoreactivation of UV-induced DNA lesions also plays a prominent role in the relative rates of bacterial inactivation by emissions from different lamps . Lamps made in Chile, such as Philips brand lamps and one type of General Electric lamp, produce far less UVB + UVC and fail to kill recA-uvrB- bacteria . In contrast, all tested lamps manufactured in the USA, Hungary, and Japan exhibit readily observed deleterious biological effects . When an E . coli recA-uvrB-phr- (photolyase-negative) triple mutant is used for assay, lethal radiations are detected from all lamps, and single-hit exponential inactivation rates rather closely correlate to amount of directly measured UVB + UVC output of each pair of lamps . Although all lamps tested may meet international and United States standards for radiation safety, optimal practices in lamp manufacture are clearly capable of decreasing human exposure to indoor UV light. Environ Mol Mutagen, 1996, 27(4), 270 - 305 SOS chromotest results in a broader context: empirical relationships between genotoxic potency, mutagenic potency, and carcinogenic potency; White PA et al.; Environmental monitoring requires that large numbers of samples be processed in a relatively short period of time . While microbioassays facilitate rapid testing, the results are often difficult to interpret in the broader context of human or animal health . Determining the consequences of exposure to genotoxic substances will ultimately require in situ monitoring of exposed organisms . However, it is immediately possible to construct a broad empirical framework within which available microbioassay results can be interpreted . To do this for SOS Chromotest results, we investigated the empirical relationships between SOS genotoxic potency and mutagenic potency (as measured with the Salmonella/microsome assay), as well as between genotoxic potency and carcinogenic potency (as measured using standard, chronic animal bioassays) . Strong relationships were identified between; 1) genotoxic potency and mutagenic potency for 268 direct-acting substances (r2=0.76) and 2) genotoxic potency and mutagenic potency for 126 S9-activated substances (r2=0.65) . Ordinary least squares regression analyses of the SOS genotoxicity-Salmonella mutagenicity relationship revealed a significant effect of SOS genotoxicity as well as differences in mutagenic potency that can be attributed to the Salmonella strain used to measure mutagenic potency . Analyses of S9-activated substances revealed a significant interaction between the SOS genotoxic potency (SOSIP) effect and the Salmonella strain effect . Two regression models relating SOS genotoxicity and Salmonella mutagenicity were used to predict the mutagenic potency of several industrial effluent extracts previously analyzed for SOS genotoxicity by White et al . {(1996): Environ Mol Mutagen 27:116-139} . Predictions are consistent with published mutagenic potency values for similar industrial waste materials . A consistent relationship was also identified between genotoxic potency and carcinogenic potency for 51 substances . Linear regression analyses revealed an effect of SOS genotoxic potency as well as differences in carcinogenic potency that may be attributable to experimental animal and route of exposure . The correlation between genotoxicity and carcinogenicity was fairly weak (maximum r value = 0.51) . Previous studies revealed similar strength of association between Ames mutagenicity and carcinogenicity . Predicted carcinogenic potencies of previously examined genotoxic, industrial effluent extracts are generally low compared to the pure substances included in the data set. Thorax, 1996 Jan, 51(1), 104 - 5 A malignant pleural effusion infected with Salmonella enteritidis; Gill GV et al.; A patient is described with a unilateral pleural effusion persistently infected with Salmonella enteritidis . The infection was eventually eradicated with ciprofloxacin . A computed tomographic scan and mediastinal lymph node biopsy demonstrated an underlying small cell bronchogenic carcinoma. Med Pr, 1996, 47(2), 133 - 41 {Test for the effects of mutagenic toxic fungal metabolites originating from municipal landfill sites}; Bubak A et al.; The purpose of the study is to assess the mutagenic effect of mycotoxins produced by moulds growing on municipal landfill sites . Mutagenicity of toxic fungal metabolites was determined by the Salmonella plate incorporation assay with two strains of bacteria: TA98 and TA100, with and without metabolic activation . The results obtained indicate that there is a severe hazard caused by these mycotoxins detected main by TA98 with metabolic activation . The most mutagenic mixture of mycotoxins acting directly on both strains was produced by Aspergillus nidulans . The highest mutagenic effect detected by TA98 with metabolic activation was found in the mixture of mycotoxins produced by one of three isolated Aspergillus fumigatus varieties. West Afr J Med, 1996 Jan-Mar, 15(1), 24 - 30 Salmonella typhi infection in Schistosoma mansoni infected mice; Njunda AL et al.; Aspects of the biology of Salmonella typhi in concurrent infection with Schistosoma mansoni in mice was studied . 0.2ml of 1 x 10(6) per S . tyhi was inoculated intraperitoneally into mice harbouring different developmental stages of S . mansoni . The rate of bacterial growth, the distribution and duration of the bacterial infection in mice and in Schistosome, as well as the drug (Chloramphenicol) response of the bacteria were studied . S . typhi was cultured more frequently in schistosome-infected mice than in mice that were not infected with schistosme (P < 0.05) . The bacterial growth rate was more rapid in mice infected with older schistosomes . Similarly the bacteria persisted much longer in mice infected with adult S . mansoni (8 weeks old) than those infected with younger (2 and 4 weeks old) schistosomes . The results of treatment of S . typhi infected mice previously infected with schistosomes of different ages made us to conclude that adult schistosomes (8 weeks old) are more relevant in the modified response to treatment of patients with S . typhi infection with concurrent Schistosoma mansoni infection. Int J Food Microbiol, 1996 Jan, 28(3), 341 - 50 Rapid detection and enumeration of Salmonella in chicken carcass rinses using filtration, enrichment and colony blot immunoassay; Hoszowski A et al.; A strategy was developed for 24-h detection and enumeration of Salmonella spp . on processed chicken carcasses . Carcasses were rinsed with saline and the rinses spiked with known numbers of serogroup B, C, D or E Salmonella . The total rinse volume was passed through two filter units of decreasing pore size . These removed most of the extraneous material while permitting rapid passage of more than 77% of the Salmonella . At least 100 ml of the filtrate was passed through a third filter unit containing a nitrocellulose capture membrane . Captured bacteria were selectively enriched by incubating the nitrocellulose membrane on filter pads soaked in Rappaport-Vassiliadis broth and then on pads soaked in brilliant green broth containing sulfadiazine and novobiocin . A colony blot immunoassay using two anti-Salmonella monoclonal antibodies was used to identify and enumerate the captured Salmonella . As few as five Salmonella colony forming units per carcass rinse could be detected . An evaluation of this system with 24 field samples indicated that the specificity was comparable to and the sensitivity higher than that of standard culture procedures. J Vet Med Sci, 1996 Jan, 58(1), 77 - 8 Recent characterization of Salmonella strains isolated from chickens in Zambia; Tuchili L et al.; Among the 23 Salmonella strains isolated from 21 diseased chicken and 2 embryonated eggs in 6 poultry farms near Lusaka City in Zambia, serovars identified were S . Gallinarum (11 strains), S . Agona (7 strains), S . Alamo (1 strain), S . Infantis (1 strain), S . Virginia (1 strain), S . Haifa (1 strain), and S . Dublin (1 strain) . S Gallinarum was detected at the highest incidence and from all the poultry farms . Fourteen serovars have been reported for the chickens in Zambia so far . Three serovars (S . Alamo, S . Haifa, S . Virginia) were newly identified in this study. J Pediatr Surg, 1996 Jan, 31(1), 127 - 30; discussion 130-1 Acalculous cholecystitis in children; Tsakayannis DE et al.; Acalculous cholecystitis (AC) is a rare disease in children, and its spectrum has not been well established . Twenty-five children with AC were identified (treated between 1970 and 1994) by retrospective clinical and pathological review . The authors recognized two distinct forms of this disease: acute (duration of symptoms < 1 month) and chronic (duration > 3 months) . Thirteen children had acute AC . Seventy-five percent were males; the age range was from 2 months to 20 years . Of these cases, six occurred in the immediate postoperative period, five were in association with a systemic medical illness, and two had an infectious cause (Salmonella) . The mean time of onset of symptoms ranged from 4 to 30 days after surgery or hospitalization (mean, 16 days) . All children presented with fever, right-upper-quadrant pain, and vomiting . Other manifestations included jaundice (38%) and right-upper-quadrant mass (23%) . Most had leukocytosis (76%) and abnormal liver function test results (62%) . Ultrasonography was the most commonly used radiological test, and all 10 cases tested met the ultrasonographic criteria for acute AC . Cholecystectomy was performed in nine children, and pathological examination confirmed cholecystitis . No postoperative complications occurred . The other four children were managed nonoperatively with intravenous antibiotics . One died, but the other three recovered fully . Twelve children had chronic AC . Sixty-seven percent were females; the age range was 7 to 18 years . All presented with chronic symptoms of right-upper-quadrant pain and nausea or vomiting . The leukocyte count and results of liver function tests were normal . Seventy-five percent had evidence of abnormal gallbladder function (noted by a radionuclide hepatobiliary scan or cholecystography) . All children in this group underwent cholecystectomy, with pathological confirmation of chronic inflammation . No complications occurred, and all patients had complete resolution of symptoms . The authors conclude that AC in children occurs in two distinct patterns . The acute and chronic forms differ in their clinical setting and presentation . Cholecystectomy is effective treatment of AC, although there may be a role for nonoperative management in selected cases. Environ Mol Mutagen, 1996, 27(3), 227 - 36 Spiral Salmonella assay: validation against the standard pour-plate assay; Diehl M et al.; The spiral Ames assay, an automated approach to bacterial mutagenicity testing which simplifies the test procedure and reduces the amount of drug required to generate mutagenic dose-response information, has been evaluated and validated for routine screening . The spiral plater delivers the Salmonella bacteria, exogenous metabolic activation system and drug to the surface of a rotating agar plate one on top of another in such a way that a uniform density of bacteria is exposed to a logarithmically decreasing volume of drug . Following an incubation of 48 hr at 37 degrees C, the plates are scanned by a laser counter, and the data are subjected to a computerized analysis . Petri plates of 15 cm diameter were used to provide a concentration range of about 250-fold per plate . The Salmonella were concentrated 20-fold to increase sensitivity . Thirty-eight compounds from a variety of chemical classes, including both pharmaceuticals and known mutagens of moderate to strong potency, were tested in both the spiral and the standard pour-plate assays . There was overall test agreement on positive or negative results for 82% of the compounds tested . When only the results from strains TA98 plus TA100 were considered, the agreement was 87% . When positive results were obtained, the fold increase over vehicle control was on average twice as great for the spiral assay compared to the pour-plate assay . It was concluded that the two assay procedures generally provided comparable results, with the spiral assay being somewhat more sensitive in terms of dose-response than the pour-plate assay. Environ Mol Mutagen, 1996, 27(3), 211 - 8 Study of the forces of stabilizing complexes between chlorophylls and heterocyclic amine mutagens; Dashwood R et al.; Chlorophyllin (CHL), a water-soluble derivative of chlorophyll, forms molecular complexes with heterocyclic amine mutagens in vitro . In a previous study {Dashwood and Guo (1993): Environ Mol Mutagen, 22:164-171}, we observed an inverse correlation between the binding constants of several mutagen-CHL complexes and the antimutagenic potency of CHL in the Salmonella assay . The present investigation utilized molecular mechanics methods of energy minimization and spectrophotometric titration to examine structural features of chlorophylls, chlorins, and porphyrins that might be important for complex formation with heterocyclic amines . The exocyclic amine group of the mutagen aligned consistently with acid groups in CHL, suggesting that H-bond or electrostatic interactions facilitate complex formation . Replacement of the exocyclic amine with a nitro group abrogated this specific orientation and raised the minimized energies of the complexes . No relationship was found between complex strength and the specific positions of amine or methyl groups on the mutagen . However, the presence of methyl groups increased the minimized energies and lowered the binding constants of the complexes, perhaps due to partial disruption of pi-pi interaction by steric effects . All of the compounds examined, including chlorophyll a, required the presence of pi-pi interactions to form stable complexes with the heterocyclic amines . In general, the present results were in agreement with the inhibitory potency of each compound in the Salmonella assay, and they provide further support for the hypothesis that chlorophylls in the diet might act as interceptor molecules of food-borne carcinogens and mutagens. Environ Mol Mutagen, 1996, 27(1), 67 - 74 Effects of the nitro-group on the mutagenicity and toxicity of some benzamines; Chung KT et al.; The Ames Salmonella/microsomal assay was employed to test the mutagenicity of some benzamines (aniline, and o- and p-phenylenediamine) and their nitro-derivatives (p-nitroaniline, 2-nitro-p-phenylenediamine, 3- and 4-nitro-o-phenylenediamine), using strains TA98 and TA100 and their nitroreductase-deficient mutants, TA98NR and TA100NR, in the presence and absence of rat S9 mix . The addition of the nitro-group to benzamine molecules converted them into direct mutagens . Furthermore, the position of the nitro-group affected their mutagenic activities . Cytotoxicity testing with Chinese hamster ovary cells (CHO-K1) showed that the presence of the nitro-group in these compounds had no specific effect on toxicity . The test compounds all showed a dose-related increase in inducing chromosomal aberrations in CHO cells . However, the presence of the nitro-group did not affect potency in inducing chromosomal aberrations . Compounds containing the nitro-group had higher initial oxidation potentials and dipole moments (mu) than their nonnitro-containing counterparts . The mutagenicity and toxicity of these compounds were not related to physico-chemical properties, including oxidation potential, energy difference (deltaE) between the lowest unoccupied molecular orbital (LUMO) and the highest occupied molecular orbital (HOMO), ionization potential (I.P.), and mu. Environ Mol Mutagen, 1996, 27(1), 19 - 29 Molecular characterization of mutation and comparison of mutation profiles in the hprt gene of Chinese hamster ovary cells treated with benzo{a}pyrene trans-7,8-diol-anti-9,10-epoxide, 1-nitrobenzo{a}pyrene trans-7,8-diol-anti-9,10-epoxide, and 3-nitrobenzo{a}pyrene trans-7,8- diol-anti-9,10-epoxide; Zhan DJ et al.; Both 1- and 3-nitrobenzo{a}pyrene (nitro-BaP) are environmental contaminants, potent mutagens in Salmonella, and moderate mutagens in Chinese hamster ovary (CHO) cells . The mutagenicity of their oxidized metabolites,trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-epoxy -7,8,9,10-tetrahydro-1-nitrobenzo{a}pyrene (1-nitro-BaP-DE) and trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-3-nitrobenzo{a}- pyrene (3-nitro-BaPDE), together with trans-7,8-dihydroxy-anti-9, 10-ep- oxy-7,8,9,10-tetrahydrobenzo{a}pyrene (BaP-DE), was determined in CHO-K1 cells, and the resulting mutations at the hprt locus were characterized by polymerase chain reaction (PCR) amplification of reverse-transcribed hprt mRNA, followed by DNA sequence analysis . The mutant frequencies, in mutants/10(6) clonable cells, at 30 and 100 ng/ml, were BaP-DE, 248 and 456; 1-nitro-BaP-DE, 68 and 260; 3-nitro-BaP-DE, 81 and 232, respectively . In general, the three diolepoxides exhibited similar mutational spectra: 1) 64% (23/36 sequenced mutants) of BaP-DE, 53% (19/36) of 1-nitro-BaP-DE, and 64% (23/36) of 3-nitro-BaP-DE mutants resulted from simple base pair substitution, with the predominant mutation being G-->T transversion; 2) 90%, 100%, and 100% of mutations at G:C had the mutated dG on the nontranscribed DNA strand; and 3) about one quarter of the mutants produced by each mutagen had one or more PCR products with partial or complete exon deletions . The mutagens induced few frameshifts or complex mutations . Among the differences in mutational specificity for the three diolepoxides, the proportion of substituted dGs with 3' purines was significant (P < 0.05) for BaP-DE (16/19, 84%) and 3-nitro-BaP-DE (17/20, 85%), but not significant for 1-nitro-BaP-DE-induced mutants (11/17, 65%, P > 0.05) . Also, high proportions of BaP-DE and 3-nitro-BaP-DE base pair substitutions at G:C occurred in DNA sequence contexts of 5'-GG-3', 5'-GGA-3', and 5'-TGGA-3', while the proportions of 1-nitro-BaP-DE mutants in these contexts were often lower . The results indicate that nitro substitution at C1 or C3 of BaP-DE reduces mutational potency in CHO cells and appears to have only subtle effects upon the mutational pattern in the hprt gene. Vet Med (Praha), 1996 Jan, 41(1), 25 - 31 {The effect of acidification on Salmonella enteritidis in a defined medium}; Ruzickova V; Effects of five acids on three highly virulent strains of Salmonella enteritidis in a defined medium were investigated at various inoculum sizes . The following minimal inhibition concentrations (MIC) were found for the acids: citric and tartaric-0.2%, pH 4.0 and 3.8, respectively; acetic and propionic-0.1%, pH 4.5 and 4.6, respectively; hydrochloric-0.05%, pH 3.6 . Bactericidal effect was evident in the organic acids at the concentration 0.4% within the pH range 3.3-3.9, and in the hydrochloric acid at the concentration 0.025%, pH 2.5 (Fig . 2, Tab . I) . As to the intensity of inhibition at MIC for Salmonella suspensions with cell densities 7 to 8 logs per ml, the acids were arranged into the following ascending order: citric < tartaric < propionic < acetic < hydrochloric . The respective order for the cell densities 6 to 7 log per ml was: propionic < tartaric < hydrochloric < citric < acetic . The mean difference between the initial and the final count of salmonellae was -1.3 to -1.8 log and -2.5 to -4.6 log for the weakest and the strongest acids, respectively (Tab . II) . Differences not only between the acids, but also between the strains, depending on inoculum sizes, were found at the nearest-to-MIC lower concentrations (subMIC) . The weakest effects at subMIC were found in propionic (0.05%; pH 5.0) and citric (0.1%; pH 4.5) acids . Tartaric acid (0.1%; pH 4.5) did not stop the growth of salmonellae at cell densities 1.7 to 2.6 log per ml, but, unlike the former two, inhibited strain II (food isolate) and strain III (egg isolate) at cell densities 0.5 and 0.6 log per ml, respectively . The strains survived the acidification with acetic acid at cell densities 4.6 to 4.9 log per ml, but the densities decreased by 1.3 to 1.7 log . Hydrochloric acid (0.025%; pH 4.6) inhibited strains II and III already at 2.3 to 3.0 log per ml, whereas strain I (human carrier isolate) was relatively acid-fast even at 1.7 log per ml . Limiting factors in the acid inhibition of salmonellae include not only the type, concentration and dissociation rate of the acid, but also the amount of the exposed Salmonella cells. J Endod, 1996 Jan, 22(1), 9 - 12 Interleukin-8 gene expression by human dental pulp fibroblast in cultures stimulated with Prevotella intermedia lipopolysaccharide; Nagaoka S et al.; Interleukin (IL)-8 mRNA expression was investigated in human dental pulp fibroblast cultures after stimulation with lipopolysaccharide (LPS) prepared from Prevotella intermedia and inflammatory cytokines . The expression of IL-8 mRNA and the release of IL-8 induced by P . intermedia LPS in pulpal fibroblast cultures were detected by Northern blot analysis and ELISA, respectively . The sufficient concentration of P . intermedia LPS on the IL-8 mRNA expression was 0.1 microgram/ml in pulpal fibroblast cultures . IL-8 mRNA levels began to increase after 2 h of exposure, reached a maximum at 4 to 8 h, and declined after 48 h, reaching the unstimulated level by 60 h . IL-8 production by the pulpal fibroblasts began to increase after 8 h of exposure upon stimulation with 10 microgram/ml of P . intermedia LPS . By contrast Salmonella LPS and synthetic lipid A did not increase IL-8 mRNA concentrations in pulpal fibroblast cultures . Recombinant human IL-1 alpha, beta, and tumor necrosis factor-alpha were capable of stimulating these cells to express IL-8 mRNA but natural human interferon-beta, gamma, and recombinant human IL-6 were incapable in our assay . These results suggest that pulpal fibroblasts are immunoresponsive cells and can elaborate IL-8 upon stimulation with P . intermedia LPS. Environ Mol Mutagen, 1996, 27(2), 152 - 61 Genetic toxicology assessment of HI-6 dichloride; Putman D et al.; The oxime HI-6 dichloride {1-(2 hydroxyiminomethyl -1-pyridino)-3-(4-carbamoyl-1-pyridino)-2-oxapropane dichloride monohydrate} has shown to be a potent reactivator of cholinesterase activity and may have efficacy for the treatment of organophosphate intoxication {SIPRI, 1976; Schenk et al.; Arch Toxicol 36:71-81, 1976} . As part of a preclinical safety assessment program, the genetic toxicology of HI-6 dichloride was evaluated in a series of assays designed to measure induction of gene mutations and chromosomal aberrations . HI-6 dichloride gave negative responses in the Salmonella mutagenicity assay and in the CHO/HGPRT gene mutation assay . Dose-dependent increases in the frequency of chromosomal aberrations were noted when HI-6 dichloride was tested in cultured CHO cells and in cultured human peripheral blood lymphocytes . The mouse lymphoma gene mutation assay, reputed to measure both gene mutations and chromosomal deletions, was negative in the absence of metabolic activation . Depending on the criteria employed, a negative or equivocal response was seen in the presence of rat liver-derived S-9 mix . An in vivo rat bone marrow metaphase assay performed to further investigate the in vitro clastogenic responses was negative . The results from these studies indicate that HI-6 dichloride does not induce gene mutations in vitro; however, it is clastogenic in vitro but does not appear to be clastogenic in vivo. Mutat Res, 1996 Jan, 367(1), 1 - 10 Genotoxicity evaluation of norethisterone acetate; Dhillon VS et al.; Genotoxic evaluation of a commonly used progestogen, norethisterone acetate, was undertaken using a combination of short-term in vitro and in vivo assays . The clastogenic potentiality of norethisterone acetate was evident from the chromosome aberrations and sister chromatid exchanges induced both with and without S9 mix in cultured human lymphocytes and also from the increased frequency of micronuclei formation and sister chromatid exchanges in mice . However, in the Ames Salmonella assay, both with