Carcinogenesis, 1990 Nov, 11(11), 2059 - 61 Formation of cyclic deoxyguanosine adducts in Chinese hamster ovary cells by acrolein and crotonaldehyde; Foiles PG et al.; Acrolein and crotonaldehyde are alpha,beta-unsaturated carbonyl compounds that form 1,N2-propanodeoxyguanosine adducts when reacted with DNA in vitro . These compounds are mutagenic in Salmonella, and crotonaldehyde is tumorigenic in rats . This study used immunoassay and 32P-postlabeling methods to determine if acrolein and crotonaldehyde form these adducts in cultured mammalian cells . Adduct levels were highest in Chinese hamster ovary cells exposed to acrolein (1 mM) with 162 mumol adduct/mol deoxyguanosine . Crotonaldehyde (10 mM) formed adduct at a level of 75 mumol/mol deoxyguanosine . 32P-Postlabeling analysis confirmed the presence of adducts in crotonaldehyde-treated cells . Persistence studies showed that adduct levels were unchanged if the cells were cultured for 6 h before DNA isolation . Mutagenicity studies were performed to determine the biological consequences of these adducts . Mutations were not observed due to the toxicity of the compounds. Circ Shock, 1990 Nov, 32(3), 209 - 18 Effect of leukotriene receptor antagonists on vascular permeability during endotoxic shock; Cook JA et al.; Evidence has accumulated that sulfidopeptide leukotrienes are significant pathogenic mediators of certain hematologic and hemodynamic sequelae of endotoxic shock . In the present study, the effects of a selective LTD4/E4 receptor antagonist, LY171883 (LY), or a selective LTD4 receptor antagonist, SKF-104353 (SKF), were assessed on splanchnic and pulmonary localization of 99mTechnetium-labeled human serum albumin (99mTc-HSA) in acute endotoxic shock in the rat . Dynamic gamma camera imaging of heart (H), midabdominal (GI), and lung regions of interest generated time activity curves for baseline and at 5-35 min after Salmonella enteritidis endotoxin (10 mg/kg, i.v.) . Slopes of GI/H and lung/H activity (permeability index, GI/H or lung/H X 10(-3)/min) provided indices of intestinal and lung localization . Rats received LY (30 mg/kg, i.v.), LY vehicle (LY Veh), SKF (10 mg/kg), or SKF vehicle (SK Veh) 10 min prior to endotoxin or endotoxin vehicle . In rats receiving the LY Veh and endotoxin (n = 8) or SKF Veh and endotoxin (n = 12), the splanchnic permeability indices to 99mTc-HSA were increased 11.2-fold and 5.1-fold, respectively (P less than 0.05) compared to vehicle control groups not given endotoxin (n = 5) . Pulmonary permeability index for 99mTc-HSA was increased (P less than 0.05) to a lesser extent (3.2-fold) by endotoxin compared to vehicle controls . Pretreatment with SKF reduced the mesenteric permeability index to control levels (P less than 0.05) during the 5-35 min time interval post-endotoxin . LY reduced the mesenteric permeability index by 70% . Pulmonary relative permeability to 99mTc-HSA was not affected by LY pretreatment . Both splanchnic and lung relative permeability to the isotope was transient; at 135-225 min post-endotoxin, splanchnic localization of 99mTc-HSA (n = 4) was not significantly different from vehicle controls in these vascular beds . Relative localization of 99mTc-labeled red blood cells (RBC) in the splanchnic or lung region was not significantly altered by endotoxin (n = 7) or LY pretreatment (n = 6) compared to vehicle controls (n = 6) . In additional studies, small intestinal luminal content of 99mTc-HSA and 111Indium (In)-labeled RBC were determined after i.v . administration of the isotopes, in a 4 cm segment of the upper small bowel . Radioactivity in the luminal lavage was normalized to activity in blood of the same animal . Endotoxin at 2 hr induced a 2.3-fold increase transluminal leakage of 99mTc-HSA (n = 5; P less than 0.03) compared to LY Veh (n = 5) or control (n = 5) rats.(ABSTRACT TRUNCATED AT 400 WORDS) Farmaco, 1990 Nov, 45(11), 1219 - 28 Biological studies on 2,1-benzisothiazole derivatives . I . Evaluation of antibacterial, antifungal and genotoxic activities of 1-acyl-3-acylimino-2,1-benzisothiazolines; Zani F et al.; The in vitro evaluation of antibacterial, antifungal and genotoxic activities of some 1-acyl-3-acylimino-2,1-benzisothiazolines is described . Compounds 55, 58, 60 and 62 exhibited a selective antibacterial activity . Compounds 1, 2, 30, 59 and 63 were active against Botrytis cinerea, compounds 6, 20, 39 and 54 against Pythium irregulare . DNA-damaging activity in the Bacillus subtilis rec-assay was demonstrated for compounds 45, 46, 54, 55, 57 and 61 . By the Salmonella-microsome assay, genotoxic activity was confirmed and demonstrated also for compounds 10, 28, 29, 40, 44, 47-53, 56, 58-60, 62 and 63 . Relationships between structure and genotoxic activity showed that all compounds containing an aromatic -NO2 group, except compound 27, were active . Among derivatives containing a -CH2Cl group in the acylic chain, only compound 40 showed mutagenic activity. J Immunol, 1990 Nov 1, 145(9), 2920 - 4 The role of IFN-gamma in the pathology of experimental endotoxemia; Heinzel FP; Proinflammatory cytokines provoked by circulating bacterial LPS mediate many of the destructive host responses characteristic of septic shock . To determine if the lymphokine IFN-gamma has a similar pathogenic role during endotoxic shock, mice were pretreated with murine rIFN-gamma (rMuIFN-gamma) at various times relative to challenge with Salmonella enteritidis LPS . Subsequent mortality was increased when rMuIFN-gamma was administered before or up to 4 h after endotoxin challenge . Pretreatment with rMuIFN-gamma resulted in nearly fivefold increases in serum TNF during endotoxemia, but TNF levels were unaffected by IFN administered after endotoxin . The increased levels of serum TNF probably reflected enhanced translation of this factor, as tissue expression of TNF mRNA did not increase correspondingly in IFN-pretreated mice . To examine the role of IFN-gamma produced endogenously during endotoxemia, mice were pretreated with 0.5 mg of anti-IFN-gamma mAb before endotoxin injection . This treatment significantly reduced mortality from endotoxic shock but caused only minor decreases in serum TNF . Anti-IFN-gamma administered 2 h after endotoxin was similarly protective . These results demonstrate a significant role for IFN-gamma in the pathology of septic shock, both indirectly as an activator of monokines known to promote lethality and possibly by other, late-acting mechanisms. Res Microbiol, 1990 Nov-Dec, 141(9), 1173 - 7 Supplement 1989 (n . 33) to the Kauffmann-White scheme; Le Minor L et al.; This supplement reports the characters of 18 new Salmonella serovars recognized in 1989 by the WHO Collaborating Centre for Reference and Research on Salmonella: 11 were assigned to S . enterica subsp . enterica, 3 to subspecies salamae, 1 to subspecies arizonae, 2 to subspecies houtenae and 1 to S . bongori. Res Microbiol, 1990 Nov-Dec, 141(9), 1151 - 62 rRNA gene restriction patterns and plasmid analysis as a tool for typing Salmonella enteritidis; Martinetti G et al.; We have evaluated the usefulness of ribosomal RNA gene restriction patterns and of plasmid analysis for the typing of Salmonella serotype enteritidis isolates . Strains were isolated from single patients excreting the organism for up to about 4 months, as well as from clusters of patients who had probably been exposed to the same source of infection . The sensitivity of ribosomal DNA (rDNA) analysis was dependent on the restriction enzyme used; of 14 different enzymes, only SmaI and SphI showed different rDNA patterns . Differences were detected between clusters, but all strains belonging to a given cluster showed identical rDNA patterns . In one single strain (isolated at day 66), we observed an SphI pattern that was not identical to that of the original isolate from the same patient . Strains were also typed by plasmid analysis . All strains harboured a plasmid of approximately 55 kb with identical restriction patterns . Smaller plasmids of 4.5 and 4.3 kb were isolated from all the strains belonging to one and two clusters, respectively . We have demonstrated that the analysis of rRNA genes is a sensitive and useful method for epidemiological typing of Salmonella serotype enteritidis, which can be complemented by analysis of plasmids if such structures are present. J Antimicrob Chemother, 1990 Nov, 26(5), 689 - 94 Effects of ampicillin, ceftriaxone, chloramphenicol, pefloxacin and trimethoprim-sulphamethoxazole on Salmonella typhi within human monocyte-derived macrophages; Chang HR et al.; The killing effect of various antimicrobial agents used in the therapy of Salmonella typhi infection was tested against Salm . typhi strain Ty2 after phagocytosis by human monocyte-derived macrophages . The macrophages, cultured in 96-well microtitre plates, were infected for 1 h at 37 degrees C by opsonized Salm . typhi Ty2 at a bacteria-cell ratio of 9:1 . When added to the infected macrophage monolayers, at one and ten times the MIC, ampicillin, ceftriaxone and pefloxacin appeared to be highly bactericidal (less than 0.25 log10 cfu/well after 20 h, against 4 log10 cfu/well in antibiotic-free controls) . Trimethoprim-sulphamethoxazole was bactericidal at ten times the MIC, but not at the MIC . Chloramphenicol was mostly bacteriostatic at the concentrations tested . As a control, gentamicin (10 mg/l) did not exhibit any significant antibacterial effect, indicating that most or all the bacteria recovered from lysed cells were intracellular . Other controls for phagocytosis were also performed with heat-killed Candida albicans . Our results seem to correlate with the known clinical effect of some antimicrobials in human Salm . typhi infection . The in-vitro assay described here may be useful for assessing the activity of antimicrobial agents against Salm . typhi infection. Zh Mikrobiol Epidemiol Immunobiol, 1990 Nov, (11), 56 - 9 {The characteristics of the O-specific humoral immune response of mice vaccinated with Salmonella choleraesuis antigens}; Vaneeva NP et al.; The work deals with the results of the comparative enzyme immunoassay (EIA) of serum samples taken from (CBA X C57BL/6) F1 mice immunized with O-specific polysaccharides, O-antigens (O-Ag) obtained by Boivin's method and antigenic preparations isolated with hydroxylamine (HA) from S . choleraesuis and S . typhimurium . O-Ag and lipopolysaccharide (LPS) of the corresponding bacterial species were used as antigens for the sensitization of polystyrene plates . The primary and secondary humoral immune response was studied by means of EIA . As revealed in this investigation, the immunization of mice with HA-isolated antigenic preparations and O-Ag, obtained from S . typhimurium, in a single injection (in doses of 1-100 micrograms) led to the development of weak specific immune response to O-Ag . Response to LPS was absent . After the second immunization of the animals pronounced immune response to O-Ag and LPS was observed . It developed as a response of both IgM and IgG type . The immunization of mice, made in a single injection, with HA-isolated antigenic preparations and O-Ag, obtained from S . choleraesuis, did not lead to the development of O-specific immune response . After the immunization of mice with these antigens in two injections sharply pronounced nonspecific activity of IgM and IgG serum antibodies with respect to O-Ag and LPS of homologous and heterologous bacterial species was noted in EIA . Neither S . typhimurium O-polysaccharide, nor S . choleraesuis O-polysaccharide did not induce O-specific immune response even after the second immunization. J Clin Microbiol, 1990 Nov, 28(11), 2409 - 14 Detection of a novel fimbrial structure on the surface of Salmonella enteritidis by using a monoclonal antibody; Thorns CJ et al.; A fimbrialike structure expressed on the surface of Salmonella enteritidis was identified by using a monoclonal antibody (69/25) produced against intact S . enteritidis cells . Fimbriae were less than 5 nm in diameter and carried a protein consisting of subunits with a molecular weight of 14,300 . No hemagglutinating activity associated with the fimbriae was detected . An epitope on the fimbrial antigen identified by monoclonal antibody 69/25 was expressed by all 58 S . enteritidis strains, 12 of 36 S . dublin strains, and a single strain of S . moscow examined . None of 169 other isolates tested from 17 salmonella serogroups expressed this epitope. J Infect Dis, 1990 Nov, 162(5), 1087 - 95 Protective effects of polyclonal sera and of monoclonal antibodies active to Salmonella minnesota Re595 lipopolysaccharide during experimental endotoxemia; Nys M et al.; Mice were passively immunized with sera from blood donors active for rough lipopolysaccharides (LPS), the J5 (Rc chemotype) mutant of Escherichia coli O111:B4, and the Re595 (Re chemotype) mutant of Salmonella minnesota . All protected the mice against lethal challenge with smooth E . coli WF96 LPS, E . coli and Salmonella rough mutant LPS, or free lipid A . Epitopes recognized by monoclonal antibodies (MAbs) reacting with the LPS of S . minnesota Re595 or lipid A were localized in the 2-keto-3-deoxy-D-manno-octulosonic acid (KDO) region and on lipid A . Core-reactive MAbs reacted with their homologous Re LPS and with free lipid A . One, GL11, cross-reacted with the KDO alone . MAbs GL6, GL11, L.4, L.6, and L.8 protected the actinomycin D-sensitized mice against the lethal effects of LPS from E . coli WF96, Salmonella enteritidis, E . coli J5, S . minnesota Re595, and free lipid A . The GL11 antibody was also protective when injected after LPS challenge . These results indicate that antibodies directed against the core glycolipid of S . minnesota Re595 LPS may be useful as an additive form of therapy that may enable decreased mortality during gram-negative bacterial sepsis. Lancet, 1990 Oct 13, 336(8720), 891 - 4 Comparison of enteric-coated capsules and liquid formulation of Ty21a typhoid vaccine in randomised controlled field trial; Levine MM et al.; In a randomised, double-blind, controlled field trial in Santiago, Chile, 81,621 schoolchildren aged 5-19 years received three doses, within a week, of attenuated Salmonella typhi oral vaccine Ty21a in enteric-coated capsules or in a new liquid suspension, or placebo . Over 36 months of surveillance, the liquid formulation (76.9% vaccine efficacy) was significantly superior to the enteric-coated capsules (33.2% vaccine efficacy) . The liquid formulation protected young children (5-9 years) (efficacy 82.3%) as well as older children (efficacy 69.3%), whereas the capsules significantly protected only older children . The liquid suspension was easy to prepare by mixing lyophilised vaccine with buffer in water and was easily administered, even to the youngest children . Thus, the liquid formulation of Ty21a is preferable to enteric-coated capsules. Med Clin (Barc), 1990 Oct 6, 95(11), 401 - 5 {Hospital outbreak of salmonellosis with secondary cases}; Vaque J et al.; Food poisoning by Salmonella in hospitals and other health care centers is not uncommon and occasionally results in high mortality rates . We report an outbreak of food poisoning that took place in June 1987 in a hospital . A staff relay was primarily affected, with an attack rate of 59.3% . The mean incubation period was 31.2 hours . The epidemiological evidence pointed to a rice with milk served as a dessert as the transmitting vehicle, although the contamination source could not be identified . Subsequently, 11 days after the start of the outbreak, 9 cases were identified among the patients cared for at the center, which were considered as secondary cases . The causative organism was Salmonella (serovariety enteritidis, phage type A) . All the involved individuals had a favorable outcome . The transmission of the mentioned organism within the hospital milieu has not been previously reported . In food poisoning developing in health care centers, the exposed individuals should be extremely careful and absolutely conscious of the need for complying with hygienic rules . In our area, we recommend sick leave while symptoms persist or the culture of feces is positive. Lancet, 1990 Oct 6, 336(8719), 831 - 4 Outbreak of diarrhoea due to Escherichia coli O111:B4 in schoolchildren and adults: association of Vi antigen-like reactivity; Viljanen MK et al.; During six days in November, 1987, 611 pupils (age range 7-19 years) and 39 adults (23-57) at a school complex in southern Finland had diarrhoea due to Escherichia coli O111:B4 . Diarrhoea developed in 137 other household members during the two weeks after the school outbreak . The source of the organism remains unknown . The outbreak strains, when incubated at 22 degrees C or exposed to ampicillin, lost the lipopolysaccharide O antigen and began to react with antisera against Salmonella typhi Vi antigen . The Vi antigen-like reactivity increased the adherence of the organisms to Hep-2 cells . These results indicate that E coli O111:B4, and possibly other enteropathogenic E coli strains, should be considered in the diagnosis of all diarrhoea cases and not only in infantile diarrhoea . Expression of Vi antigen in E coli may play a part in virulence by enhancing adherence to the intestinal epithelium. J Appl Bacteriol, 1990 Oct, 69(4), 493 - 7 Heat resistance in Salmonella enteritidis phage type 4: the influence of storage temperatures before heating; Humphrey TJ; Storage of cultures of Salmonella enteritidis PT4 at either 4 degrees or 8 degrees C before heating significantly increased heat sensitivity . The differences between fresh and stored cultures, which became apparent after 4-7 h, were more pronounced with cultures stored at the lower temperature and in those heated at 60 degrees rather than 55 degrees C . Incubation of the stored cultures in either egg or Lemco broth for 30 min at 37 degrees C prior to heating enabled the organisms to recover heat resistance. J Appl Bacteriol, 1990 Oct, 69(4), 477 - 80 Prevalence of Salmonella in chicken carcasses in Portugal; Machado J et al.; During 1986-87 57% of 300 chicken carcasses yielded salmonellas where tested by a swabbing method . Serotypes isolated were Salmonella enteritidis (66%), Salm . agona (12%), Salm . newport (6%), Salm . saintpaul (6%), Salm . derby (4%), Salm . typhimurium (3%), Salm . bardo (1%), Salm . ohio (1%) and untypable (2%) . The results are compared with those of avian and human salmonellosis registered in Portugal during the same period. Avian Dis, 1990 Oct-Dec, 34(4), 991 - 3 Isolation of Salmonella enteritidis from internal organs of experimentally infected hens; Gast RK et al.; Tissues from experimentally infected hens were examined for the presence of Salmonella enteritidis (SE) . SE was recovered from internal organs of both orally inoculated hens and hens infected by horizontal contact transmission . SE was isolated from 58% of the ceca, 51% of the livers, 47% of the spleens, 17% of the ovaries, and 17% of the oviducts of hens sampled during the first 5 weeks after exposure . SE was recovered at a low frequency from all internal organs sampled for as long as 22 weeks after exposure. Nervenarzt, 1990 Oct, 61(10), 626 - 8 {Abscess of the thyroid gland caused by Salmonella enteritidis in immunosuppressive treatment of generalized myasthenia gravis with thymoma}; Zimmermann CW et al.; We report the case of a 69-year old male caucasian patient who developed a lateral neck tumor while under immunosuppression with azathioprine . The tumor was diagnosed finally as an abscess caused by Salmonella enteritidis after isolation of the agent from blood, tumor biopsy and feces . This extremely rare manifestation of an infection by Salmonella enteritidis is considered as a complication of immunosuppressive therapy. Int J Food Microbiol, 1990 Oct, 11(2), 135 - 41 Estimation of most probable number of Salmonella in retail samples of minced pork; Sinell HJ et al.; The number of salmonellae in 174 samples of minced pork was determined by the Most Probable Number (MPN) method in two separate laboratories . The material examined was taken from a collection of samples which were Salmonella positive in an earlier study . The MPN estimation was carried out using portions of original samples which had been divided (2 x 100 g) before the initial examination and which had been deep frozen and stored for 1 to 14 weeks at -18 degrees C until re-examination . Of the 174 samples initially positive for Salmonella, 131 (75.3%) were positive on re-examination using pre-enrichment in buffered peptone water (BPW) and selective enrichment in Rappaport-Vassiliadis medium (RV) and in tetrathionate medium according to Muller-Kauffmann (MK) . The majority of the samples gave Salmonella counts below 1000/100 g (96.7% at lab . A and 97.3% at lab . B) . Comparison of the results from both laboratories showed good agreement in the distribution pattern of the frequencies within the MPN classes, but agreement between the same sample pair was poor (r = 0.23) . RV medium proved to be superior to the MK medium. Kansenshogaku Zasshi, 1990 Oct, 64(10), 1361 - 5 {Typhoid fever with intestinal hemorrhage, drug-induced fever, DIC, ARDS and psychiatric disorder (a case report)}; Ohnishi K et al.; A 40-year-old poor nutritional Japanese male was admitted to our hospital on June 5, 1989, with a 31-day history of fever . He had been working as a crew member of a ship in South East Asia . Salmonella typhi was isolated from his blood culture . In the course of the disease, intestinal hemorrhage, drug-induced fever and liver dysfunction, DIC, ARDS, and psychiatric disorder were identified . Intestinal hemorrhage occurred after the coagulation test became normal, so it was thought that the intestinal hemorrhage did not correlate with DIC . The patient was treated with CP, ABPC and supportive therapy . He became well, and ARDS and psychiatric disorder were disappeared . He was discharged on the 118th day of illness . Drug-induced fever was thought as one of the allergic reaction and the causative drug was not identified by LST . It was suspected that psychiatric disorder correlated with poor nutrition . Supportive therapy such as mandatory bed rest, intravenous hyperalimentation and low-volume blood transfusions, as well as an antimicrobial treatment were important for the inhibition of shock and/or intestinal perforation. Kansenshogaku Zasshi, 1990 Oct, 64(10), 1355 - 60 {Production and characterization of a monoclonal antibody specific for Salmonella O19-antigen}; Yamaura N et al.; A monoclonal antibody, SBY1 (IgM, kappa), against the Salmonella O-antigen was generated by using the myeloma cell line Sp2/O-Ag14 as a fusion partner with spleen cells from BALB/c mice immunized with S . senftenberg 963 K . SBY1 was characterized by the slide agglutination and absorption test . SBY1 was believed to show the specificity to O1-, O3- or O19-antigens of Salmonella because S . Senftenberg 963 K (O1, 3, 19) was used as the antigen for immunization . The slide agglutination test with the Salmonella serovars indicated the responsiveness of SBY1 . SBY1 was reactive only with strains that possessed O19-antigen . The agglutinating ability of SBY1 was absorbed completely with bacilli possessing O19-antigen . These finding indicates that SBY1 is specific for O19-antigen . Polyclonal factor sera for he serotyping of the O3, 10 group of Salmonella cross-reacted with Salmonella group O1, 3, 19 in the slide agglutination test . In contrast, SBY1 did not cross-react with serovars from several other Salmonella groups . These data suggest the usefulness of SBY1 as a serodiagnostic tool for serotyping of Salmonella. J Antimicrob Chemother, 1990 Oct, 26 Suppl B, 181 - 6 The efficacy and safety of pefloxacin in the treatment of typhoid fever in Algeria; Ait-Khaled A et al.; The efficacy and safety of pefloxacin 400 mg twice daily for seven days in the treatment of typhoid fever was investigated in an open, non-comparative study involving 37 patients infected with Salmonella typhi . Between day 5 and the end of treatment, all patients showed clinical improvement . The clinical cure rate at the end of the treatment period was 89.2% . One month after the end of treatment, the final assessment showed a clinical cure rate of 94.6% with relapses occurring in only two patients . Both these patients belonged to the group with negative blood cultures but positive serodiagnostic tests . Bacteriological tests confirmed eradication of the pathogen in 94.6% of patients and the relapses in the two serologically positive patients . Temperature became normal in a mean of 5.14 days . Clinical adverse reactions were reported in 5.9% (3/51) of patients (vomiting in two, transient pruritic rash in one) . The results of this study indicate that a seven-day course of pefloxacin 400 mg twice daily provides a suitable alternative in the treatment of typhoid fever. FEMS Microbiol Immunol, 1990 Oct, 2(3), 179 - 85 Suppressive effect of lipid A partial structures on lipopolysaccharide or lipid A-induced release of interleukin 1 by human monocytes; Wang MH et al.; Experiments were designed to investigate the significance of lipid A partial structures, precursor Ia (compound 406), and lipid X (compound 401) to serve as antagonists of interleukin 1 (IL-1) release from human mononuclear cells and monocytes induced by lipopolysaccharide (LPS, endotoxin) of Salmonella abortus equi or synthetic Escherichia coli lipid A (compound 506) . A definite inhibition mediated by lipid A partial structures on IL-1 release induced by LPS or lipid A was found in repeated experiments . The inhibitory effect was exerted not only on IL-1 release, but also on IL-1 peptide synthesis at the intracellular level . The results also show that lipid A partial structures have suppressive effects even when added 1-4 h after LPS or lipid A . We conclude from these results that lipid A partial structures (precursor Ia and lipid X) have potent immunomodulatory effects on LPS- and lipid A-induced IL-1 release and may become useful reagents to study the mechanism of interaction of LPS and lipid A with cells of the immune system. J Biol Response Mod, 1990 Oct, 9(5), 480 - 91 Biological response to intravenously administered endotoxin in patients with advanced cancer; Engelhardt R et al.; The purpose of the study was to evaluate the toxicity and biological activity of highly purified lipopolysaccharide (LPS) administered intravenously to cancer patients in order to establish an optimum dosage scheme . An initial subtoxic dose was increased in weekly increments in accordance with individual regimens that maintained patient reaction at a safe and acceptable level . Purified LPS from Salmonella abortus equi was administered to 11 patients with advanced solid tumors on a weekly schedule with intraindividually escalating dosage as determined by patient response . Biological response was monitored by complete blood count, C-reactive protein, and cytokine measurements at different time points after LPS injection . Tumor necrosis factor-alpha (TNF) and interleukin-1 beta serum levels were measured by enzyme-linked immunosorbent assay and interleukin-6 (IL-6) by bioassay . Dose-limiting toxicities including chills and fever (WHO grade III) were reached at 1.0 ng/kg of body weight (maximal tolerated dose-1, MTD-1) . Pretreatment with ibuprofen (1,600 mg) abrogated these side effects, allowing further escalation of LPS doses up to 10 ng/kg of body weight . At dose levels greater than 8.0 ng/kg of body weight (MTD-2), the aforementioned side effects occurred again and, additionally, hepatic toxicity (WHO grade III) was observed . Hematological changes included neutropenia followed by a pronounced neutrophilia contributed to by up to 30% bands, marked monocytopenia for 3 h, and retarded lymphopenia . By 24 h, all hematological parameters returned to pretreatment values . TNF serum levels increased from 10 pg/ml before treatment to 7,000 pg/ml as a function of dosage . Maximum serum levels were reached at 60 to 90 min after LPS injection . Similarly, IL-6 serum concentrations increased from less than 4 to 2,500 U/ml; peak levels were obtained 30 min after TNF peak values . Prior administration of ibuprofen had no effect on the above-mentioned hematological changes nor on cytokine release . LPS can be administered intravenously in weekly intervals at escalating doses from 0.15-10.0 ng/kg of body weight, when patients are protected by pretreatment with ibuprofen at dose levels above 1.0 ng/kg of body weight . Cytokine release as measured by TNF and IL-6 increased in a dose-dependent manner although the constitutional symptoms are completely attenuated. Circ Shock, 1990 Oct, 32(2), 113 - 22 Dexamethasone and indomethacin treatment during endotoxicosis in the suckling rat; Goto M et al.; Gram negative sepsis/septic shock continues to be a major cause of morbidity and mortality in newborns . We studied the effects of anti-inflammatory drugs, indomethacin (IND) and dexamethasone (DX), on glucoregulation, body weight, and mortality in 10-day-old suckling rats administered Salmonella enteritidis lipopolysaccharide (LPS) . IND (1.5 mg/kg) or DX (4 mg/kg) was intraperitoneally (ip) administered immediately after highly lethal LPS injection . Both IND and DX attenuated the LPS-induced hypoglycemia and lactacidemia, and decreased the mortality, IND did not alter body weight changes in rats with septic shock . DX continued a catabolic state and reduced their body weights . In rats fasted for 24 hr before LPS injection, DX, but not IND, increased the mortality . We concluded that IND and DX improved the LPS-induced glucose dyshomeostasis and decreased the mortality of endotoxic shock in 4-hr-fasted 10-day-old rats . Per contra, DX was detrimental in 24-hr-fasted 10-day-old endotoxic rats. Pediatr Infect Dis J, 1990 Oct, 9(10), 715 - 7 Nosocomial bacteremias in measles; Hussey G et al.; The purpose of this study was to determine whether nosocomial bacteremias occurred more frequently in patients admitted with severe measles compared with general pediatric admissions . In a retrospective survey of 977 blood culture reports during a 4-year period, 1985 to 1988, the incidence of nosocomial bacteremias in patients with measles was found to be on the average of 3.37/100 admissions/year, approximately 6 times that of general pediatric patients (0.57) . Gram-negative organisms (predominantly Klebsiella and Salmonella species) accounted for 86.5% of all isolates from measles patients, with 23% of these being multiply antibiotic-resistant . All the isolates from the general patients were fully susceptible to antibiotics . The duration of hospitalization was more than doubled in both groups of affected patients . The onset of hospital-acquired bacteremias occurred on an average of 11.2 days after admission in the patients with measles and 20.5 days in the general patients . Our findings revealed that nosocomial bacteremias occurred with greater frequency in patients with measles and contributed to the morbidity of these patients. Mutat Res, 1990 Oct, 242(2), 121 - 5 Evaluation of the mutagenic potential of endosulfan using the Salmonella/mammalian microsome assay; Pandey N et al.; The mutagenic potential of endosulfan, a polychlorinated insecticide, was assessed using the highly sensitive Salmonella tester strains TA97(a), TA98, TA100 and TA102 . It exhibited a toxic effect at dose levels of 50 micrograms/plate and higher . Plate incorporation studies did not show mutagenic response with any of the tester strains used . A modification of the assay using a preincubation procedure showed mutagenic activity with and without metabolic activation with TA97(a) only . Increased toxicity was observed after addition of phenobarbital-induced S9 mix. Mutat Res, 1990 Oct, 242(2), 101 - 10 Evidence for an acetoxyarylamine as the ultimate mutagenic reactive intermediate of the carcinogenic aromatic amine 2,4-diaminotoluene; Cunningham ML et al.; 2,4-Diaminotoluene (2,4-DAT) is a mutagenic and hepatocarcinogenic aromatic amine, requiring metabolic activation . We have found that the mutagenic potency of 2,4-DAT in Salmonella TA98 is similar when activated by either Aroclor-1254-induced rat primary hepatocytes or 9000 x g supernatant . Previous work has demonstrated that 2,4-DAT is activated by cytochrome P450 . The present report describes an investigation of the role of acetyltransferase in 2,4-DAT activation . Substitution of TA98 with the acetyltransferase-deficient strain TA98/1,8-DNP6 resulted in an approximately 90% decrease in the mutagenic potency for 2,4-DAT using S9 activation . The newly engineered acetyltransferase-enhanced Salmonella tester strain YG1024 (TA98(pYG219} demonstrated greatly enhanced sensitivity to the mutagenicity of 2,4-DAT . Inhibition of O-acetyltransferase activity, either with the selective acetyltransferase inhibitor thiolactomycin, or by competitive inhibition with an alternative substrate for the enzyme, reduced the mutagenicity of 2,4-DAT in this acetyltransferase-enhanced bacterial strain . From these data we conclude that following 2,4-DAT activation by N-hydroxylation by cytochrome P450, the resulting hydroxylamino intermediate is further activated in the bacteria via O-acetylation to form the ultimate reactive intermediate, which is postulated to be 4-acetoxyamino-2-aminotoluene. J Clin Pathol, 1990 Oct, 43(10), 863 - 5 Comparison of methods for the diagnosis of typhoid fever; Duthie R et al.; Over five years the Bactec radiometric blood culture method yielded Salmonella typhi in 41 of 45 confirmed cases of typhoid fever, 90% of which were from the first culture set taken . Blood clot culture was positive in 18 (41%) of 44 confirmed cases and stool culture in 24 (59%) of 41 . The yield from 2189 Widal clot cultures was only 0.03% . There were 68 positive results in 2258 unpaired Widal tests: 23 of them were falsely positive and 13 falsely negative, but in 11 out of 68 cases the Widal was the only positive laboratory test . It is concluded that routine clot culture is not cost effective if a sensitive blood culture method is used, and that the Widal test is useful only in selected patients. Am Rev Respir Dis, 1990 Oct, 142(4), 782 - 8 Effect of recombinant hirudin, a specific inhibitor of thrombin, on endotoxin-induced intravascular coagulation and acute lung injury in pigs; Hoffmann H et al.; We hypothesized that thrombin activation may play a prominent role in endotoxin-induced secondary organ failure, such as acute lung injury . To test this hypothesis, we administered a thrombin-specific inhibitor, recombinant hirudin, in endotoxemic pigs . The pigs were anesthetized, mechanically ventilated, and prepared with Swan-Ganz and extravascular lung water (EVLW) catheters . A total of 18 randomly selected animals received a pretreatment of 1,000 U/kg of hirudin, followed by a continuous infusion over 6 h of 500 U/kg/h given simultaneously with the infusion of 10 micrograms/kg/h of Salmonella abortus equi endotoxin . Another 18 animals received a continuous infusion over 6 h of endotoxin but did not receive hirudin . All animals were fluid resuscitated with 17 ml/kg/h of saline for the duration of the experiment . Data are expressed as the mean (95% confidence interval) . Hirudin reduced the endotoxin-induced consumption of plasma fibrinogen from -110 (-138 to -82) mg/100 ml to -39 (-67 to -12) mg/100 ml (p = 0.0001) and endotoxin-induced increases in the soluble fibrin in plasma from 434 (369 to 499) ng/ml to 236 (171 to 300) ng/ml (p = 0.0002) . These data suggest an effective inhibition of the endotoxin-generated thrombin by hirudin . Furthermore, hirudin significantly reduced endotoxin-induced increases in pulmonary vascular resistance from 32 (27 to 37) kdyn x s x cm-5 x kg to 20 (15 to 25) kdyn x s x cm-5 x kg (p = 0.0015) and increases in EVLW from 15.4 (13.2 to 17.6) ml/kg to 12.2 (10.0 to 14.4) ml/kg (p = 0.0299).(ABSTRACT TRUNCATED AT 250 WORDS) Mutat Res, 1990 Oct, 234(5), 289 - 302 Salmonella test: relation between mutagenicity and number of revertant colonies; van der Hoeven N et al.; This paper describes a model that relates the actual effect measured in the Salmonella test, i.e., the number of revertant colonies, to the mutation rate induced by a stable test compound having no side effects and acting without a time-lag . A maximum-likelihood estimator for the mutation rate is derived . Furthermore some side effects (mortality, increase in generation time, other mutations) are included in more extensive models . Side effects can cause a non-linear dose-response relation . Factors delaying the effect of the compound lead to an apparently higher mutation rate if a higher histidine dose is applied or a smaller inoculum is used . Factors slowly decreasing the effect of the compound reverse this result . Secondary effects of the test compound on the bacteria result in a non-linear dose-response relationship. Mutat Res, 1990 Oct, 232(2), 249 - 60 Use of a composite polyfunctional model electrophile as a probe to analyze the performance of an artificial intelligence structure-activity method; Rosenkranz HS et al.; The CASE structure-activity relational method was applied to the model polyfunctional electrophile proposed by Ashby and associates . The predicted activities from data bases of 'structural alerts', mutagenicity in Salmonella and rodent carcinogenicity were compared . It was thus found that the predictive efficacy of CASE was increased when it employed a combination of human and artificial intelligence, as exemplified by the CASE analysis of 'structural alerts. Mutat Res, 1990 Oct, 232(2), 243 - 8 Metabolic activation of quercetin mutagenicity; Vrijsen R et al.; The mutagenicity of quercetin was reinvestigated using the Salmonella/microsome test . The mutagenicity of quercetin was enhanced by the cytosolic fraction of liver extract (S100), or by ascorbate, and even more by the complete liver supernatant (S9) in the presence of cofactors (NADP and glucose-6-phosphate) . The formation of metabolites by the S9 enzymes was demonstrated by reverse-phase HPLC. Epidemiol Infect, 1990 Oct, 105(2), 307 - 16 Salmonella colonization in commercial pet turtles (Pseudemys scripta elegans); Shane SM et al.; An epidemiological survey was conducted on two commercial turtle farms in southern Louisiana to determine the reason for an apparent increase in the prevalence of Salmonella spp . in turtle hatchlings at the time of pre-export certification examination . Pond water was consistently found to be contaminated (6/36 samples) with either Salmonella newport, S . arizonae, or S . poona . Environmental specimens obtained from eggs and turtle hatcheries (204 specimens) failed to yield Salmonella spp . A sample comprising 197 hatchlings, derived from a batch previously demonstrated to be contaminated, showed a salmonella prevalence of 12%, with S . arizonae and S . poona the only serotypes isolated . Four serotypes of Salmonella sp . isolated by a certifying laboratory in 1988, and 20 salmonella isolates obtained from hatchling turtles, were all resistant to gentamicin . The emergence of gentamicin resistance in Salmonella spp . isolated from turtles will reduce the effectiveness of preventive measures in use in Louisiana since 1984. Carcinogenesis, 1990 Oct, 11(10), 1811 - 8 Response of the ke test to NCI/NTP-screened chemicals . I . Non-genotoxic carcinogens and genotoxic non-carcinogens; Bakale G et al.; The response of a physico-chemical carcinogen-screening test, the k(e) test, to 46 rodent carcinogens and 20 putative non-carcinogens that had been screened in long-term two-species bioassays by the National Cancer Institute/National Toxicology Program are reported . All of the chemicals screened are those that yield mutagenicity responses in the Ames Salmonella/microsome test that are either equivocal or contrary to the rodent carcinogenicity responses . The electron attachment rate constants, k(e)S, of the test chemicals in cyclohexane at 21 degrees C were measured using a pulse-conductivity technique . The k(e)S of 27 of the 46 rodent carcinogens (59%) are equal or greater than the diffusion-controlled k(e) of carbon tetrachloride, which is regarded as the boundary between a positive and negative response; the k(e)S of 8 of the 20 mutagenic non-carcinogens (40%) are less than diffusion-controlled . If the boundary between positive and negative k(e) responses is decreased to half the diffusion-controlled k(e), six additional carcinogens yield a positive ke response which increases the k(e) test sensitivity to 72% while the specificity to non-carcinogens remains at 40% . Comparison of these k(e)S with measures of the chemicals' electrophilicity that had been inferred from chemical structure indicates that k(e) provides a markedly different measure of electrophilicity and one that complements the Ames Salmonella assay . The use of the k(e) test as an analytical tool to indicate the presence of electron-attaching impurities in solvents such as benzene is discussed, as is the sensitivity of the k(e) test to rodent-liver carcinogens. Zhonghua Yi Xue Za Zhi (Taipei), 1990 Oct, 46(4), 232 - 6 {Retrospective study of Salmonella gastroenteritis in infants}; Sheu CL et al.; Sixty-four cases of Salmonellosis were retrospectively analyzed in Jan . 1985 to Dec . 1988 at the department of pediatrics, Veteran General Hospital, Taipei . Most of the cases (78%) occurred between May and October, the most common pathogenic organism isolated was B salmonella group (65.6%) . Antibiotic susceptibility to ampicillin revealed remarkably decrease from 75% (1985) down to 11.7% (1988) and the most sensitive antibiotic agent was ceftriaxone (98.3%) . Blood culture were obtained in 42 cases and patients with salmonella bacteremia were found in 10 cases (23.8%) . Five of 17 patients under 3 month old showed positive blood culture . Four of 5 bacteremic patients were complicated individually with convulsion, failure to thrive, chronic diarrhea and one case expired . Four of 33 patients between 3 month and 1 year were bacteremic . Two of 4 bacteremic patients were respectively complicated with meningitis and hip-joint arthritis . The average duration of salmonella shedding was 37.5 days (range 4-180 days) . In conclusion: 1 . Salmonellosis hasn't decreased in the past 4 years and the resistance to ampicillin and chloramphenicol has increased . 2 . Young infants are at particular risk for bacteremia and focal complication, so if salmonellosis is suspected in infants under 3 month old, blood culture should be obtained and proper antibiotic therapy should be given. Avian Dis, 1990 Oct-Dec, 34(4), 855 - 60 Characteristics of Salmonella spp . and Escherichia coli isolated from broiler flocks classified as "good" or "poor" producers; Spears KR et al.; Cecal samples from 100 broiler flocks were cultured for Escherichia coli and Salmonella . Samples were selected from flocks classified as either "good" or "poor" producers by a production formula . In an attempt to identify predictors of flock productivity, isolates were studied for differences in antibiotic resistances, hemagglutination of erythrocytes, production of colicins, production of siderophores, type of hemolysis, resistance to host complement, and presence of plasmids . S . typhimurium (copenhagen) was isolated from one poor producing flock and three good producers . Salmonella isolates showed no significant differences in the parameters studied . The E . coli isolates showed significant differences only for the presence of plasmids . These data indicate that differences in host intestinal E . coli from good and poor producing flocks do not predict flock productivity. Zentralbl Veterinarmed B, 1990 Oct, 37(8), 599 - 610 Inflammatory reactions in the teat and udder of the dry cow; Persson K; The inflammatory reactions in the teat and udder of the dry cow were studied by total and differential somatic cell counts (SCC) and by measuring bovine serum albumin, N-acetyl-beta-D-glucosaminidase (NAGase), plasminogen and plasmin . The teat and udder cisterns were surgically separated from each other in two udder quarters of each cow . Salmonella endotoxin was infused in one teat cistern and one udder quarter, and saline was infused in one teat cistern and one udder quarter . The inflammatory response was followed by several samplings post infusion . The reactions in the dry udder quarters were mainly in line with the results of similar studies in lactating glands . The differential SCC and the NAGase results were, however, somewhat different . The teats were capable of a strong inflammatory response . Reactions different from those seen in the glands were observed with regard to permeability changes and NAGase . The experimental model used showed promising results and is suitable for further studies of the inflammatory process. Infect Immun, 1990 Oct, 58(10), 3187 - 93 Phorbol myristate acetate inhibits HeLa 229 invasion by Bordetella pertussis and other invasive bacterial pathogens; Ewanowich CA et al.; The microfilament inhibitors cytochalasins B and D have been traditionally used to indirectly evaluate the requirement for actin in the uptake of invasive bacterial pathogens by nonprofessional phagocytes . Through their effects on microfilaments, both cytochalasins also impart profound alterations in cellular morphology and surface topology, which likely interfere with adherence . Alterations affecting adherence would complicate interpretation of the effect of cytochalasins on entry alone . As an alternative to cytochalasins, the effect of the tumor promoter phorbol myristate acetate (PMA) was examined for its effects on uptake of several invasive bacterial pathogens by HeLa 229 cells . In this communication, PMA was shown to induce a similar change in HeLa cell actin distribution, but, in contrast to cytochalasins B and D, PMA had no significant effect on gross cell morphology . The modified actin distribution was shown to reduce internalization of Bordetella pertussis, Yersinia pseudotuberculosis, Shigella flexneri, and Salmonella hadar in a dose-dependent manner at concentrations ranging from 1 to 1,000 ng/ml . The magnitude of reduction at a PMA concentration of 1,000 ng/ml was greater than the reduction elicited by cytochalasin B at 2.5 micrograms/ml but was less than that elicited by cytochalasin D at 2.5 micrograms/ml . Mezerein, a functional analog of PMA, caused a similar dose-dependent reduction in uptake of B . pertussis, whereas an inactive analog of PMA, alpha-4-phorbol-12,13-didecanoate was without effect on invasion . Binding studies further reveal that pretreatment of HeLa cells with PMA or mezerein did not significantly impair the ability of B . pertussis to adhere, in contrast to cytochalasins B and D, which caused a marked reduction in adherence. Rev Clin Esp, 1990 Oct, 187(5), 218 - 22 {Acute gastroenteritis: a prospective study of 445 cases}; Moreno A et al.; Four hundred and fourty-five adult patients suffering acute gastroenteritis (AG) seen at the emergency ward of two hospitals in Barcelona, have been studied . The aim of this work was to analyze the cause of AG in our community and to evaluate the utility of the biologic and clinical criteria chosen as indicators of bacteremia or of AG produced by invasive microorganisms . Stool culture was positive in 157 patients (35%) of which 140 were Salmonella sp . The most frequently isolated serotype was S . enteritidis . Eight patients (7.8%) presented Salmonella sp . bacteremia . Presence of an underlying disease, dehydration, shivers, fever, presence of occult blood in stools, septic hemogram and the history of AG in other family members were more common in patients with a positive stool culture (p less than 0.05) . Patients with bacteremia presented dehydration with a significantly higher frequency than nonbacteremics . The rest of the parameters studied were similar in both groups . We conclude that Salmonella sp . is the most frequently encountered microorganisms responsible for adult AG in our community . It is possible to identify patients with AG due to Salmonella sp . based on clinical and biological parameters . On the contrary, it is necessary to perform a wider study in order to determine the parameters that may allow the identification of patients with bacteremia. J Struct Biol, 1990 Oct-Dec, 105(1-3), 11 - 21 Phase diagram of lipid A from Salmonella minnesota and Escherichia coli rough mutant lipopolysaccharide; Brandenburg K et al.; We have reported here on the structural polymorphism of lipid A, the "endotoxic principle" of bacterial lipopolysaccharide . For lipid A of rough mutant lipopolysaccharide from Salmonella minnesota and Escherichia coli, the three-dimensional supramolecular structures were determined with x-ray diffraction utilizing synchrotron radiation . The investigations were performed in the water concentration range 10 to 95% by weight, at {lipid A}:{Mg2+} molar ratios from 1:0 to 0.1:1, and in the temperature range from 20 to 70 degrees C . These data were correlated with measurements of the beta----alpha phase behaviour which was monitored with differential scanning calorimetry and Fourier-transform infrared spectroscopy . We found that the transition temperature of the acyl chains ranges--in the absence of Mg2(+)-from 45 degrees C at high to 56 degrees C at low water content, and-at an equimolar content of Mg2(+)-from 52 degrees C at high to 59 degrees C at low water concentrations . In the gel phase-in which the lipid A acyl chains are more disordered than those from saturated phospholipids-cubic phases are adopted at high water content (greater than 60%) and at high {lipid A}:{Mg2+} molar ratios . At low water contents, lamellar states are assumed exclusively . In the liquid crystalline state of lipid A, the hexagonal HII state is adopted under all conditions . The structural variability of lipid A is highest at high water concentrations, and structural changes may be induced by only slight changes in temperature, water content, and Mg2+ concentration . Under physiological conditions, however, the lipid A assemblies exhibit a strong preference to cubic structures. Trop Geogr Med, 1990 Oct, 42(4), 370 - 2 Septicaemia caused by an imported strain of multiply antibiotic resistant Salmonella typhi successfully treated with ciprofloxacin; Coovadia Y et al.; A case of typhoid fever caused by a multiply antibiotic resistant strain of Salmonella typhi is reported . The S . typhi strain was resistant to ampicillin, chloramphenicol and sulphamethoxazole-trimethoprim . Treatment with cefotaxime, resulted in a clinical and bacteriological cure, but the infection relapsed within a month after completion of therapy . It resolved completely with oral ciprofloxacin with no relapse after a follow up period of one year . To our knowledge this represents the first such reported case in South Africa . The role of ciprofloxacin in treating infections caused by multiantibiotic resistant S . typhi is also discussed. Cell Biol Toxicol, 1990 Oct, 6(4), 399 - 409 Formation of genotoxic products from N-nitrosoheptamethyleneimine (NHMI), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) by isolated rabbit lung cells; Dahl JE et al.; The genotoxic potentials of N-nitrosoheptamethyleneimine (NHMI), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) were studied in fresh preparations of Clara cells and type II cells isolated by centrifugal elutriation and density gradient centrifugation, and macrophages from rabbit lung . The activation of the compounds to bacterial mutagens was assayed in the Salmonella mutagenicity test using strains of TA 100 and TA 1530 preincubated with test chemicals and cells placed in chambers with nucleopore membranes to separate cells and bacteria . Unscheduled DNA synthesis was measured by incorporation of {3H}-thymidine in the cells after exposure to the compounds . NHMI, NNK and NNN were not activated to bacterial mutagens by Clara cells, type II cells or macrophages, presumably because the reactive metabolites generated were not released into the incubation medium . However, NHMI and NNK increased unscheduled DNA synthesis in Clara cells, and the highest repair activity was found after incubation with NNK . The effect of NNN was only marginal . This indicates that NHMI and NNK are genotoxic in the rabbit lung and that the Clara cells are involved in the metabolic activation of these compounds. Zh Mikrobiol Epidemiol Immunobiol, 1990 Oct, (10), 113 - 7 {The effect of modulators of free-radical oxidation on the functional activity of phagocytes}; Martynenko LD et al.; The influence of free-radical oxidation inhibitors (alpha tocopherol) and stimulators (levamisole and alriblastin) on the processes of the peroxide oxidation of lipids in blood serum and the phagocytic activity of peripheral blood neutrophils in Salmonella infection in rabbits at an early age is accompanied by phasic changes in the peroxide oxidation of lipids with activation at the early period of the development of the infection . The synchronism of changes in the peroxide oxidation of lipids and in the phagocytic activity of neutrophils is observed . Alpha tocopherol inhibits the peroxide oxidation of lipids and decreases the degree of the completeness of phagocytosis . Alriblastin stimulates the peroxide oxidation of lipids and increases the phagocytic activity of neutrophils. Microbiologica, 1990 Oct, 13(4), 317 - 21 Characterization of strains of Salmonella enterica subsp . enterica serovar Wien isolated in Italy: an epidemiological evaluation; Nastasi A et al.; In the years 1987-1988, 110 strains of Wien serovar were isolated from a gastroenteritis outbreak in a neonatal unit in Palermo (Sicily) . These strains showed different drug resistance patterns and plasmid profiles . Analysis of endonuclease restriction fragments of chromosomal DNA by hybridization with E . coli rRNA has demonstrated that a single bacterial clone or its derivatives were responsible for the outbreak . Furthermore, the study of 139 strains, isolated since 1970 from different geographic locations of the Mediterranean area, has confirmed a notable degree of homogeneity within Wien serovar, even though the detection of genetic polymorphisms in some isolates suggests that a number of distinct bacterial strains contributes to maintain the circulation of Wien serovar. Jpn J Exp Med, 1990 Oct, 60(5), 247 - 52 Mechanism of protection provided by active immunization with porins in mice challenged with Salmonella typhi; Sharma P et al.; Oxygen free radical (OFR) generation capacity of peritoneal macrophages was studied by chemiluminescent technique . Chemiluminescent (CL) response of macrophages from control, infected and immunized-infected mice was observed using non specific (Latex) and specific (S . typhi, cells and porins) stimulants at different time intervals . CL response was found to be significantly higher in immunized-infected group throughout the study period using all the three stimulants as compared to that in the infected as well as uninfected control mice . The mode of action of porin vaccine in increasing capacity of generating OFR is probably through increased expression of porin (protein) as well as carbohydrate receptors on the macrophage surface which leads to the stimulation of the whole caseade of respiratory burst or through the increase in the respiratory burst enzyme activities linked with each receptor or both. Bioorg Khim, 1990 Oct, 16(10), 1325 - 31 {Partial purification of glycosyltransferases participating in the biosynthesis of Salmonella anatum and S . kentucky O-antigens using high performance gel chromatography}; Druzhinina TN et al.; The solubilized glycosyltransferases which catalyse the biosynthesis of Salmonella anatum and S . kentucky O-specific polysaccharides were partially purified by HPLC on Superose 12 . Two mannosyl transferases from S . kentucky were separated by gel chromatography; these transferases were found useful for chemical-enzymic synthesis of polyprenylpyrophosphate derivatives of trisaccharides Tal-Man-Gal and Man-Tal-Gal. Immunol Cell Biol, 1990 Oct, 68 ( Pt 5), 299 - 305 Identification of antigens which stimulate T lymphocytes of Salmonella enteritidis 11RX immunized mice; Vordermeier HM et al.; The technique of using sodium dodecylsulfate-polyacrylamide gel electrophoresis fractionated antigens (Ag) transferred to nitrocellulose filters was adopted to analyse T cell responses to Salmonella enteritidis 11RX Ag . Employing in vitro proliferation assays with T cells from S . enteritidis 11RX-primed (BALB/c x C57BL/6J)F1 mice as the measure of T cell stimulation, we have identified Ag able to stimulate T cells in the regions containing 16, 24, 34 and 50-60 kDa proteins, with dominant Ag activity at about 16 kDa . These results were confirmed with long-term, Ag-specific L3T4+ T cell lines which responded to molecules in the same four Mr regions, suggesting that no selection by a single antigenic determinant had occurred during more than 3 months of in vitro culture, or that all the molecules which were stimulatory shared at least one antigenic determinant . Because the seven clones we examined responded only to 16 kDa molecules, the former alternative is the more likely . Standard immunoblot analysis indicated that these Ag also act as major B cell stimulating determinants . T cells of BALB/c mice, which are 5-10 times more resistant to S . enteritidis 11RX than C57BL/6J mice, showed the same pattern of reactivity as F1 mice whereas the major antigenic region for T cells of C57BL/6J mice was located between 50 and 60 kDa. J Air Waste Manage Assoc, 1990 Oct, 40(10), 1391 - 6 Effect of fuel properties on mutagenic activity in extracts of heavy-duty diesel exhaust particulate; Rasmussen RE; The effect of varying fuel properties on the emission of mutagenic materials was studied in diesel exhaust particles from a heavy duty engine run under transient speed and load conditions while using nine fuels varying in aromatics, sulfur and boiling point . Mutagenic activity of the soluble organic fraction (SOF) of the particulate was determined using the Ames Salmonella test system with strain TA98 with and without S9 activation . Increasing mutagenic activity relative to fuel consumed (mutants/lb fuel) or to engine work output (mutants/hp-h) was correlated with increasing fuel aromatics (p less than 0.05), but not with fuel sulfur . Increased fuel sulfur levels were correlated with increased amounts of SOF but with decreasing mutagenic activity of the SOF (mutants/microgram SOF) (p less than 0.05) . As a result, mutants/hp-h were essentially the same for high- and low-sulfur fuels with high aromatics . No association was found between the fuels' boiling points and the mutagenic activity of the SOF . Mutagenic activity with S9 was generally lower than without, but the correlations were not changed. J Surg Res, 1990 Oct, 49(4), 287 - 92 Cross-reactive murine monoclonal antibodies directed against the core/lipid A region of endotoxin inhibit production of tumor necrosis factor; Mayoral JL et al.; Two murine monoclonal antibodies (mAbs) directed against the core/lipid A moiety of lipopolysaccharide (endotoxin, LPS) were derived from mice immunized with either Escherichia coli J5 or Salmonella minnesota Ra, Rb, Rc, or Re heat-killed organisms or LPS . These mAbs were selected on the basis of their ability to cross-react against a panel of gram-negative bacterial LPS using Western immunotransblot analysis . We hypothesized that these anti-LPS mAbs directed against the conserved core region of LPS would inhibit LPS-induced macrophage tumor necrosis factor (TNF) production by neutralizing LPS derived from different gram-negative bacteria . To test this hypothesis, unelicited peritoneal macrophages were treated with either mAb 5G11 (deep core/lipid A specificity, broad LPS cross-reactivity) or mAb 5B11 (intermediate core specificity, limited LPS cross-reactivity) . Macrophages were then challenged with a panel of LPS, and TNF activity was measured by the use of the L929 cytotoxicity assay . MAb 5G11 significantly inhibited TNF production against a panel of different types of LPS, but mAb 5B11 did not . In addition, mAb 5G11 did not inhibit TNF production due to isolated lipid A stimulation, suggesting that mAb 5G11 neutralized LPS by binding primarily to the deep core region of LPS . MAb 5G11 was also able to inhibit TNF production if added within 10 min of LPS stimulation but had no effect at 30 min, suggesting that macrophage stimulation may be irreversible during even the early stages of the response to LPS.(ABSTRACT TRUNCATED AT 250 WORDS) Ugeskr Laeger, 1990 Sep 24, 152(39), 2849 - 51 {Diarrhea acquired abroad--traveller's diarrhea . Admissions to Medical Department C, Odense Hospital, during the period 1977-1988}; Holmskov U et al.; A total of 106 out of 267 patients admitted with acute gastroenteritis to Medical Department C, Odense Hospital, during the period 1977-1988 had acquired the condition abroad . This group was investigated retrospectively . During the period of investigation, the number of patients with "traveller's diarrhoea" increased but compurized constantly approximately 40% of the patients admitted with acute gastroenteritis . The patients were investigated routinely for pathogenic intestinal bacteria and parasites and the etiology could be determined in 72% . Salmonella infections were found in 50% and 1/5 of these were caused by Salmonella typhi or Salmonella paratyphi . Double and triple infections occurred . 51% of the infections were acquired in Asia and Africa although less than 7% of Danish package tours visit these regions . Five patients (5%) developed serious complications. Carbohydr Res, 1990 Sep 19, 205, 125 - 32 Synthesis of methyl 3-O-(alpha-D-glucopyranosyl)-7-O-(L-glycero-alpha-D- manno-heptopyranosyl)-L-glycero-alpha-D-manno-heptopyranoside; Garegg PJ et al.; The title trisaccharide glycoside, which is related to part of the core region of the lipopolysaccharide from Salmonella, and the disaccharide glycosides methyl 3-O-alpha-D-glucopyranosyl-L-glycero-alpha-D-manno-heptopyranoside and methyl 7-O-L-glycero-alpha-D-manno-heptopyranosyl-L-glycero-alpha-D-manno- heptopyranoside have been synthesised . Methyl 2,3,4-tri-O-benzyl-L-glycero-alpha-D-manno- heptopyranoside, obtained via a one-carbon elongation at C-6 of methyl 2,3,4-tri-O-benzyl-alpha-D-manno- hexodialdo-1,5-pyranoside, was used as precursor both for the heptosyl donor and acceptor. Med J Aust, 1990 Sep 17, 153(6), 330 - 2, 334-5 Invasive disease due to Salmonella virchow: a north Queensland problem; Ashdown LR et al.; Salmonella virchow is the second most commonly isolated salmonella serotype from human sources in Australia, and overseas studies indicate that S . virchow is a significant cause of extraintestinal salmonellosis . The successful management of three infants, two with septicaemia and one with leptomeningitis and septicaemia due to S . virchow, is described . A review of the Townsville General Hospital laboratory records (1978-1988) showed that, among other aspects, S . virchow accounted for 46% of all salmonella septicaemias, further exemplifying the invasive propensity of this serotype . Information obtained from various sources, after crude analyses, demonstrates that more than 90% of S . virchow infections in humans in Australia occur in Queensland, and that most (greater than 78% in 1987) of those infections in Queensland come from a coastal zone north of Bundaberg, with the highest concentration (0.4 per 1000 persons) occurring in the Cairns region. Biochem Pharmacol, 1990 Sep 15, 40(6), 1317 - 22 Leukocyte alterations do not account for hepatitis induced by endotoxin or TNF alpha in galactosamine-sensitized mice; Tiegs G et al.; Subtoxic doses of endotoxin (salmonella abortus equi lipopolysaccharide, LPS) (5 micrograms/kg i.p.) or tumor necrosis factor alpha (TNF alpha) (15 micrograms/kg i.v.) induced fulminant hepatitis within 8 hr, when mice had been sensitized by a subtoxic dose of D-galactosamine (700 mg/kg i.p.) . LPS-treatment led to the release of TNF into the circulation, independently of the presence of D-galactosamine . The TNF-dependent development of hepatitis was accompanied by a severe lymphopenia and neutrophilia as assessed by leukocyte differential count . The total leukocyte count was not significantly affected . Lymphopenia and neutrophilia were induced by LPS or TNF alpha alone; however, the differential count was not influenced by D-galactosamine . A quantity of 260 micrograms/kg phorbol myristate acetate (PMA) i.p . or 5 micrograms/kg platelet activating factor (PAF) i.v . or 3.3 mg/kg N-formyl-methionyl-leucyl-phenylalanine methylester (FMLP) i.v . or 167 mg/kg zymosan i.v . also caused lymphopenia and neutrophilia in mice . However, none of these agents induced the production of systemic TNF and therefore failed to induce hepatitis in D-galactosamine-sensitized mice . In LPS-insensitive C3H/HeJ mice administration of LPS produced neither differential count changes nor hepatitis while both events were observed when TNF alpha was given . This shows that TNF alpha alone gives rise to lymphopenia/neutrophilia as well as hepatitis independent of LPS . When the action of TNF alpha was blocked by anti TNF alpha antiserum pretreatment of LPS-sensitive mice, the animals were protected against LPS-induced hepatitis . However, lymphopenia and neutrophilia still occurred to a similar extent . The involvement of a putative additional mediator of LPS-induced leukocyte alterations was checked . The findings suggest that this mediator, if present, is different from IL-1, IL-2, eicosanoids or superoxide . We conclude from our findings that changes in leukocyte numbers and composition following D-galactosamine LPS or D-galactosamine/TNF alpha administration is an epiphenomenon rather than a causal event of leukocyte stimulation in the process of inducing a fulminant hepatitis in mice. Carbohydr Res, 1990 Sep 5, 204, 93 - 102 Isolation and characterisation of 3-deoxy-D-manno-2-octulopyranosonate 7-(2-aminoethyl phosphate) from the inner core region of Escherichia coli K-12 and Salmonella minnesota lipopolysaccharides; Holst O et al.; The title compound (PE-Kdo) was isolated after hydrolysis of the lipopolysaccharides of Escherichia coli K-12 strain W3100 and Salmonella minnesota strains R4 and R7, and the location of the 2-aminoethyl phosphate group at position 7 was established by 13C-n.m.r . spectroscopy . Derivatives of PE-Kdo were acetylated, silylated, and methylated in order to evaluate their usefulness for analysis by g.l.c.-m.s. J Infect Dis, 1990 Sep, 162(3), 763 - 4 Heterogeneity of lipopolysaccharide phenotype among Salmonella typhi strains; Jimenez-Lucho V et al.; Comparison of the Vi antigen, lipopolysaccharide, and protein components of the cell surface of three strains of Salmonella typhi showed that differences in lipopolysaccharide contributed most to distinctions in serum survival, whereas differences in Vi antigen content had no apparent effect. Antimicrob Agents Chemother, 1990 Sep, 34(9), 1715 - 9 Clinical isolate of a porinless Salmonella typhi resistant to high levels of chloramphenicol; Toro CS et al.; We studied a clinical isolate of Salmonella typhi (strain 1895) characterized by resistance to 200 micrograms of chloramphenicol per ml despite the absence of chloramphenicol-inactivating activity . The outer membrane protein profile analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated a deficiency of one of the major protein species which may serve as a porin for entry of chloramphenicol . When the strain was transformed with a plasmid encoding chloramphenicol acetyltransferase, chloramphenicol added to the culture was not inactivated, suggesting a drastic reduction of permeability towards the drug . Moreover, transformants bearing a plasmid coding for the Escherichia coli OmpF porin became considerably more susceptible to chloramphenicol (40 micrograms/ml) . On the other hand, transformants carrying a plasmid encoding the Salmonella typhi ompC gene remained as resistant to the drug as the parental strain, even though they overexpressed OmpC . These findings indicate that the lack of OmpF plays a major role in the resistance to chloramphenicol in strain 1895. Antibiot Khimioter, 1990 Sep, 35(9), 22 - 6 {Antibiotic resistance plasmids in Salmonella strains isolated from various sources}; Vakulenko SB et al.; Resistance of 60 Salmonella strains to aminoglycoside antibiotics was studied . It was found that 51 strains had a multiple resistance to the antibiotics used . By the antibiotic resistance phenotypes, the strains were divided into three major groups . Analysis of the extrachromosomal DNA revealed the presence of plasmids in 48 antibiotic resistant strains and 6 antibiotic sensitive strains . The plasmids transferred by conjugation to the E . coli recipient from 21 antibiotic resistant strains . The 150-kb plasmids transferred in all the strains . The 100-kb plasmids additionally transferred in 5 strains . The high molecular weight plasmids that transferred to the recipient strain by conjugation encoded resistance to all the aminoglycosides used. J Assoc Off Anal Chem, 1990 Sep-Oct, 73(5), 734 - 42 Improved hydrophobic grid membrane filter method, using EF-18 agar, for detection of Salmonella in foods: collaborative study; Entis P; A collaborative study was carried out in 30 laboratories to validate improvements to the official final action hydrophobic grid membrane filter (HGMF) screening method for Salmonella in foods, 985.42, by comparing the performance of the improved HGMF method against that of the AOAC/BAM conventional culture method . Six products were included in the collaborative study: milk chocolate, raw deboned poultry meat, black pepper, soy flour, egg yolk powder, and nonfat dry milk . The raw deboned poultry meat was naturally contaminated with Salmonella, and the remaining 5 products were each inoculated in advance with low levels of individual Salmonella serotypes . The AOAC/BAM method produced 11 false negative results and the improved HGMF method produced 18 false negative results . The improved HGMF Salmonella method has been approved interim official first action for all foods to replace the HGMF official final action method, 985.42. Food Chem Toxicol, 1990 Sep, 28(9), 607 - 11 A study of the mutagenicity of some commercially canned Spanish mushrooms; Morales P et al.; The mutagenicity of two wild (Lactarius deliciosus and Boletus luteus) and two cultivated (Agaricus bisporus and Pleurotus ostreatus) mushrooms, preserved by canning and widely consumed in Spain, was studied in the Ames Salmonella/microsome test and in the CHO/HPRT assay system using mammalian cells . The mushroom extracts did not show mutagenicity in the microbial Ames test nor in the mammalian CHO-K1 cells, and this response was not modified by the presence of S-9 mix in the assay mixtures . Only the extracts from P . ostreatus showed a weak mutagenic activity in the CHO/HPRT assay in the presence of a metabolic activation system (S-9). Clin Rheumatol, 1990 Sep, 9(3), 411 - 3 Salmonella enteritidis causing joint sepsis; Kyle V et al.; A 22-year-old male taking dexamethasone following resection of a medulloblastoma developed an acutely painful swollen knee from which salmonella enteritidis was cultured . He had no gastrointestinal symptoms; one stool culture was positive . Active metalloproteinases without inhibitors were detected in the synovial fluid, a characteristic finding in septic joints . S . enteritidis infecting joints is extremely rare despite being the second most frequent salmonella species after S . typhimurium causing infections in man . The recent findings of S . enteritidis in eggs, and poultry points to one more source of infection . Immunosuppression is likely to facilitate infection. Poult Sci, 1990 Sep, 69(9), 1606 - 9 Presence and impact of Salmonella contamination in commercial broiler hatcheries; Cox NA et al.; Egg fragments from hatching trays, swabs of belting material, and paper pads from three broiler hatcheries were sampled for the presence and level of salmonellae . Salmonella serotypes were recovered from 71, 80, and 74% of the egg fragments, belting material, and paper pads, respectively . Overall, salmonellae were found in 75, 91, and 67% of the samples taken at Hatchery 1,2, and 3, respectively . Thirty-eight of 40 randomly selected samples contained greater than 10(3) salmonellae cells per sample . All of the Salmonella serotypes encountered in the present study had previously been isolated from poultry . The presence and persistence of salmonellae contamination in the hatchery suggests that the vulnerable day-of-hatch chick may be at a greater colonization risk in the hatchery than during grow-out . Contamination and penetration of the shell of hatching eggs may constitute the most important link (or critical control point) in the transmission of salmonellae to young birds and eventually the consumer . An effective intervention method may have to be employed at this point to break the transmission link and significantly impact the overall problem of Salmonella colonization in poultry. Scand J Soc Med, 1990 Sep, 18(3), 175 - 8 Salmonella and Shigella carriers among refugees from the middle east and Sri Lanka in Denmark; Kjersem H et al.; One per cent of ten thousand refugees were asymptomatic carriers of Salmonella and Shigella species found by a differentiated health check programme at a Danish Red Cross arrival centre in Denmark 1985 and 1986 . Six patients with typhoid fever and one with S . parathyphi-A septicaemia all fell ill within the first few weeks after arrival . A child of a chronic S . typhi carrier developed typhoid fever four months after arrival . Cases of sporadic and mild diarrhoea occurred due to Salmonella and Shigella species . The carriers were instructed in prophylactic, hygienic measures and no outbreaks developed . The health check system in this period seemed to be sufficient in relation to preventing outbreaks of infections caused by non-typhoid Salmonella and Shigella species . The relative cost-effectiveness of a more intensive S . typhi screening on arrival is questionable . The organization of health check systems should be reviewed regularly, as each refugee situation is different and will change in different periods. Rev Infect Dis, 1990 Sep-Oct, 12(5), 817 - 9 Endocarditis due to ampicillin-resistant nontyphoid Salmonella: cure with a third-generation cephalosporin; Rodriguez C et al.; A case of ampicillin-resistant salmonella bacteremia complicated by endocarditis in a 78-year-old man is presented . Previous rheumatic valvular heart disease and the lack of response to initial treatment with chloramphenicol prompted us to consider this diagnosis . There was a good clinical response after treatment with ceftriaxone alone and corresponding improvement on the echocardiogram . This case demonstrates the possible endovascular complications of salmonella bacteremia in elderly people and that endocarditis should be included among the invasive infections due to ampicillin-resistant Salmonella that could potentially be treated with the newer cephalosporins. Onderstepoort J Vet Res, 1990 Sep, 57(3), 175 - 81 Salmonella isolated from feeds and feed ingredients during the period 1982-1988: animal and public health implications; Durand AM et al.; The prevalence of Salmonella in southern Africa in farm feeds and by-products of animal origin during 1982-1988 was determined . Salmonella occurred in 5.18% of the farm feed samples and in 9.54% of the by-product samples . Different serovars were isolated, some only once . The findings underestimate the true prevalence of Salmonella in farm feeds and by-products, and is representative of only the most severely contaminated products . The epidemiology of salmonellosis is discussed with special reference to the importance of multiple resistance to antibiotics, the increase in the number of cases of salmonellosis worldwide and "Salmonella free" feeds and foods . More detailed research on the role of farm feeds in the epidemiology of salmonellosis is required . Efforts should be made to increase awareness of the problem, to improve quality management at farm feed production plants and to develop efficient systems to monitor the hygienic safety of feeds and foods. J Infect, 1990 Sep, 21(2), 195 - 203 Salmonella septic arthritis: a case report and review; Morgan MG et al.; We describe a case of septic arthritis in a child with no apparent predisposing conditions . Salmonella virchow was isolated from her knee and faeces, both isolates being identical except for the latter's resistance to ampicillin . Evidence is presented for the acquisition of ampicillin resistance in vivo, including the demonstration of the R plasmid and its ready transferability to Escherichia coli . The recent literature on the subject is reviewed and the role of group CI salmonellae in invasive disease is examined. Am Ind Hyg Assoc J, 1990 Sep, 51(9), 505 - 9 Evaluation of methods for destruction of some alkylating agents; De Meo M et al.; Destruction procedures for dimethylsulfate (DMS), diethylsulfate (DES), methyl methanesulfonate (MMS), and ethyl methanesulfonate (EMS) have been investigated using treatment by 1 N NaOH, 1 N NH4OH, 1 M Na2CO3, and 1 M Na2S2O3 . During the kinetic study of the destruction process, the determination of remaining concentrations of the alkylating agents was performed by the derivatization of p-nitrophenoxide to p-nitroanisole and p-nitrophenetole, which were separated by high performance liquid chromatography . The mutagenic activity of the destruction products was evaluated by the Ames test using Salmonella tester strains TA97, TA98, TA100, and TA102 . The kinetics of destruction in every case followed a time-dependent exponential relationship . Solutions of 1 M Na2S2O3 showed the highest capacity for destruction of the four alkylating agents, half-lives of DMS, DES, MMS, and EMS being 0.14 min, 1.26 min, 0.60 min, and 5.26 min, respectively . No mutagenic activity was detected following complete destruction in 1 M Na2S2O3. Mutat Res, 1990 Sep, 232(1), 31 - 5 Genotoxic effect of a keto-aldehyde produced by thermal degradation of reducing sugars; Valsa JO et al.; Reductone (HOCH2-CO-CHO), a keto-aldehyde formed, in alkaline pH, by thermal degradation of reducing sugars, blocks cellular respiration and macromolecular biosynthesis, inactivates far-UV (254 nm)-irradiated wild-type E . coli cells, and causes DNA strand breaks . So it may be supposed to be an inducer of SOS functions . Indeed, when Salmonella tester strains TA98, TA100 and TA102 were treated with reductone solutions, without metabolization, a mutagenic effect was detected for all of them . Besides, reductone induced lysogenic E . coli cells and cell filamentation, as measured by the Inductest and the SOS Chromotest . So reductone must be considered a genotoxic drug. J Gen Microbiol, 1990 Sep, 136 ( Pt 9), 1833 - 8 Transposon insertion mutagenesis of a genetic region encoding serum resistance in an 80 kb plasmid of Salmonella dublin; Terakado N et al.; Using transposon insertion mutagenesis with Tn1 or Tn5, we obtained Salmonella dublin mutant strains that showed either diminished serum resistance (five mutants) or diminished mouse lethality (two mutants) . Detailed restriction cleavage analysis to determine the single sites of transposon insertion in an 80 kb plasmid (pTE800) indicated that a region for serum resistance was located within a 3.0 kb region of the SalI cleavage fragment 5 and the HindIII fragment 2, while the region for mouse lethality was within a 6.0 kb region of the SalI fragment 2 and the HindIII fragment 1 . When the Tn1-containing SalI fragment 5 was reconverted, by homologous recombination, to the original SalI fragment 5 (9.6 kb), serum resistance was recovered to the same level as that of a parent strain 52401 . Moreover, the change in the serum resistance correlated with changes in the neutral sugar composition of the LPS . The mutation in the plasmid in strain TE4-55 that gave diminished mouse lethality was also reversed by recombination with the cloned SalI fragment 2 (15.0 kb), with concomitant recovery of mouse lethality . These results indicate that the genetic region for serum resistance is different from that for mouse lethality, and that the gene for serum resistance is closely involved with the expression of the neutral sugar composition of the LPS of S . dublin. Semin Immunol, 1990 Sep, 2(5), 341 - 9 Oral vaccination using recombinant bacteria; Schodel F; With the development of avirulent but immunogenic Salmonella strains it has become possible to deliver heterologous antigens to the mucosal and systemic immune system by the oral route . The basis of attenuation of different Salmonella mutants and the immune response to foreign antigens expressed by recombinant strains is discussed, as are problems related to the stabilisation of foreign genes in Salmonella and to the expression of immunogenic antigens. Rev Sci Tech, 1990 Sep, 9(3), 779 - 94 Biotechnology and veterinary science: production of veterinary vaccines; Wray C et al.; The fundamental principles of genetic manipulation are explained, as are the methods of production of vaccines of veterinary importance . Specific attenuation of micro-organisms may result from genetically-engineered mutations which produce metabolic blocks, from the development of effective bacterial toxoids and from viral gene segment reassortment . Recombinant DNA techniques have been used to produce multi-component vaccines by the insertion of genes into carrier organisms, such as pox viruses and attenuated salmonella, and also to produce subunit vaccines . The use of synthetic peptide vaccines and anti-idiotype vaccines, together with problems of parasite vaccines, are described . Biotechnology would appear to have a major role to play in the future prevention of many animal diseases. Zh Mikrobiol Epidemiol Immunobiol, 1990 Sep, (9), 77 - 80 {Enhancement of infection resistance of mice infected with Salmonella typhi by factors of immune lymph nodes}; Koval'chuk AL et al.; Mediators, secreted by lymph node cells shortly after immunization and draining the site of the injection of the antigen, produced a nonspecific activating effect on cells of the macrophagal series . The preventive injection of immune lymph node factors induced an increase in nonspecific resistance to S . typhi TU2 {correction of Ty2} No . {correction of N}4446. Res Microbiol, 1990 Sep-Oct, 141(7-8), 981 - 93 Vaccines against enterotoxigenic bacterial pathogens based on hybrid Salmonella that express heterologous antigens; Clements JD et al.; In this report, we examine two aspects in the development of a vaccine against enterotoxigenic bacterial pathogens based on hybrid Salmonella that express heterologous antigens . First, we describe the construction of a non-toxic fusion peptide for immunization against Escherichia coli that produce heat-labile (LT) and heat-stable (ST) enterotoxins . For that construction, the 5' terminus of the gene coding for ST was fused to the 3' terminus of the gene coding for the binding subunit of LT(LT-B) . The ST gene was constructed synthetically with appropriate restriction sites to permit in-frame, downstream insertion . Maximum expression of ST antigenicity was obtained when a seven-amino-acid proline-containing linker was included between the LT-B and ST moieties . The purified LT-B/ST fusion peptide consisted of a single polypeptide chain with an apparent molecular weight of 18,000 . The LT-B/ST fusion peptide was non-toxic and immunologic determinants of both LT and ST were recognized by antibodies directed against the native toxins . Animals immunized with either crude or purified preparations containing the hybrid molecule produced antibodies that were able to recognize native toxin in vitro . Significantly, these antibodies were able to neutralize the biological activity of native ST . The second aspect reported here examines a mechanism for stabilizing expression of heterologous antigens in attenuated Salmonella mutants by integration of the heterologous gene (LT-B) into the chromosome of the carrier . A comparative in vitro study of the levels of expression of LT-B between the cointegrate strain and an isogenic strain carrying the LT-B gene on a multicopy plasmid demonstrated that the initial levels of expression of both strains is similar, that the plasmid-carrying strain loses the ability to express the heterologous antigen very quickly and that the cointegrate continues to maintain and express the antigen without the requirement for a stabilizing antibiotic. Res Microbiol, 1990 Sep-Oct, 141(7-8), 945 - 53 Experimental ovine salmonellosis (Salmonella abortusovis): pathogenesis and vaccination; Pardon P et al.; Salmonella enterica subsp . enterica ser . Abortusovis, a sheep-adapted serotype, causes a contagious disease . Abortion is the major symptom and the main source of contamination . Research on this ovine disease may aid farmers, but may also contribute to comparative biological knowledge . Innate resistance partly controlled by the Ity locus, increased resistance to reinfection and humoral and T-cell-mediated immunity were observations gained with a murine model . In ewes, abortion regularly occurs following subcutaneous challenge carried out from the third month of gestation onwards . This ovine model was used to evaluate prevention methods for Salmonella Abortusovis infection . One subcutaneous injection of a live attenuated lyophilized vaccine containing a selected streptomycin-independent reverse mutant was shown to protect ewes against abortion and excretion of Salmonella Abortusovis . This vaccine could be administered simultaneously with other commercial live vaccines such as Brucella melitensis Rev . 1 vaccine . In sheep, application of the vaccine to the conjunctiva (an easy, individual and hygienic route of mucosal vaccination) was followed by lymph node bacterial colonization and a serological response without local or general clinical reactions . The early events of natural infection remain to be explored, as do the mechanisms underlying the host specificity of Salmonella Abortusovis. Res Microbiol, 1990 Sep-Oct, 141(7-8), 831 - 7 Expression of hepatitis B virus antigens in attenuated Salmonellae for oral immunization; Schodel F et al.; The aim of our work is to identify hepatitis B virus antigens that can be stably expressed in attenuated Salmonellae and elicit protective immune responses as live oral route vaccines . As a first carrier system, we expressed T-cell and B-cell epitopes of hepatitis B virus as fusion proteins with the non-toxic subunit B (LT-B) in attenuated Salmonellae . These recombinant Salmonellae elicited anti-LT-B T- and B-cell immune responses and anti-HBV nucleocapsid antigen (HBcAg) T-cell responses when fed to mice . To combine the protective potential and the high immunogenicity of HBc with the induction of virus neutralizing antibodies to HBV surface antigen, we constructed vectors expressing hybrid HBc/pre-S particles in which the pre-S epitopes were surface-exposed . With one of these vectors, stable constitutive high level expression of hybrid HBc/pre-S2 particles was achieved in several attenuated Salmonella strains . When recombinant Salmonellae expressing such hybrid HBc/pre-S2 fusion proteins were fed to mice, the animals developed high titres of anti-HBcAg-specific serum IgG after a single or multiple oral immunizations, depending on the strain used as a carrier . In addition, lower titered antibodies against the pre-S2 antibody-binding sites were elicited . This is the first HBV antigen eliciting high-titered immune responses after a single oral immunization in recombinant Salmonellae . The immunogenicity of periplasmic LT-B and cytoplasmic HBc/pre-S2 shows that surface exposure of a foreign antigen is not a prerequisite for its immunogenicity in live attenuated Salmonellae. Res Microbiol, 1990 Sep-Oct, 141(7-8), 807 - 16 Clinical and field trials with attenuated Salmonella typhi as live oral vaccines and as "carrier" vaccines; Levine MM et al.; In recent years there has been a resurgence of research to develop new and improved attenuated strains of Salmonella typhi to function as live oral vaccines against typhoid fever and to serve as "carrier" vaccines to express foreign antigens of other pathogens and deliver them to the immune system . Strain Ty21a has served as a prototype in clinical and field trials to identify the optimal formulations and dosage schedules for live vaccines and to quantitate the duration of protection that can be achieved . Clinical trials with three new attenuated S . typhi candidate vaccines, a Vi+ variant of Ty21a, an aroC,aroD double mutant recombinant strain and a cya,crp double mutant, are underway or will be initiated shortly. Microb Pathog, 1990 Sep, 9(3), 213 - 8 Dead salmonellae or their endotoxin accelerate the early course of a Salmonella infection in mice; Hormaeche CE; The course of a Salmonella infection following a low intravenous dose of virulent organisms was studied in mice . Simultaneous administration of 10(4) S . typhimurium C5 together with c . 10(8) dead salmonellae caused a marked acceleration of early net bacterial growth in the liver and spleen, leading to a rapidly overwhelming infection . Administration of similar numbers of either Staphylococcus albus or Bacillus cereus had no effect, whereas 20 micrograms of S . typhimurium Boivin-type lipopolysaccharide (B-LPS) produced an effect similar to dead organisms; 1 microgram B-LPS had a significant infection-accelerating effect . Both B-LPS and Westphal-type endotoxin (W-LPS) could enhance a salmonella infection in LPS-responsive C3H/HeMg mice, whereas only B-LPS was effective in LPS non-responder C3H/HeJ mice, implying that the infection-enhancing effect of a large bolus of dead organisms may be due in part to its LPS content . The results show that the course of a Salmonella infection following administration of large numbers of salmonellae in mice is different from that of Salmonella infections arising from small inocula . The relevance of these results to studies on the possible intracellular location of salmonellae in vivo is discussed. Southeast Asian J Trop Med Public Health, 1990 Sep, 21(3), 361 - 6 Salmonella krefeld in Thailand: II . Molecular biology of drug resistance; Jayanetra P et al.; Human salmonellosis due to Salmonella krefeld is very rare . During 1976-1978, a large outbreak of S . krefeld gastroenteritis occurred in Thailand, mainly in children . The majority of strains were multiply drug resistant with high minimum inhibitory concentration (MIC) . The MIC for these drugs were ampicillin (Ap) 256-4096 mg/l, chloramphenicol (Cm) 256-512 mg/l, kanamycin (Km) 512- greater than 4096 mg/l, streptomycin (Sm) greater than 1024 mg/l, sulfamethoxazole (Su) 4096- greater than 8192 mg/l, tetracycline (Tc) 64-128 mg/l and trimethoprim (Tp) 64-256 mg/l . Resistance to Su and Tp declined after the period of the epidemic . The resistance genes were found to be highly transferable at a rate of 10(-2) to 10(-4) . All strains with more than five resistance markers had large molecular weight plasmids of 120-140 megadaltons . The restriction profile analysis of plasmids from isolates collected from various regions of the country showed similarity of DNA fragment pattern . These isolates were resistant to Ap, Cm, Km, Sm, Su and Tc. Southeast Asian J Trop Med Public Health, 1990 Sep, 21(3), 354 - 60 Salmonella krefeld in Thailand: I . Epidemiology, infection and drug resistance; Jayanetra P et al.; Information from the National Salmonella Shigella Center (NSSC), Thailand indicated that the most frequently isolated Salmonella serotype from humans during 1974-1975 was Salmonella typhi (33.1%), during 1976-1982 was S . krefeld (26.6%) and during 1983-1987 was S . derby (12.6%) . Antimicrobial susceptibility study of various Salmonella serotypes indicated that S . krefeld was the serotype with multiple drug resistance persisting for the longest period of time . Human salmonellosis due to S . krefeld is very rare . During 1976-1978, a large outbreak of S . krefeld gastroenteritis occurred in Thailand, mainly in children . The outbreak spread countrywide and is currently endemic . Gastrointestinal symptoms are severe in young infants . Systemic invasion with bacteremia, meningitis and pneumonitis were reported . The antimicrobial susceptibility pattern of isolates varied from sensitive to multiply drug resistant . The common antibiotic resistances were to ampicillin (75-92%), chloramphenicol (33-75%), kanamycin (67-90%) and sulfamethoxazole-trimethoprim (15-52%) . Resistance to gentamicin and sulfamethoxazole-trimethoprim declined after the period of the epidemic . Antimicrobial resistance patterns of 150 S . krefeld strains isolated in Thailand during 1978-1987 showed multiple drug resistance with up to seven drugs . The most common patterns were ApCmKmSuTp and ApCmKmSmSuTc. J Clin Lab Immunol, 1990 Sep, 33(1), 7 - 9 Immunoglobulin profiles and antibacterial antibody levels in 50 patients a long time after posttraumatic splenectomy; Demeter J et al.; Serum immunoglobulin and antibacterial antibody concentrations have been determined in 50 patients 2 to 20 years after posttraumatic splenectomy . The serum levels of IgG, IgA and IgM were found to be significantly greater in the group of posttraumatic splenectomy patients than in that of the healthy controls . The serum IgE concentrations did not differ statistically from that of the controls . The serum level of natural antibodies against intestinal bacteria were found to be elevated (Shigella 1b, 2a, 3 and Salmonella typhi 02 strains) or normal (Salmonella typhi 0901 as well as E Coli 026 and 055 strains) . Our results show that the studied functional aspects of humoral immunity in this group of otherwise healthy splenectomized individuals were not impaired. Res Microbiol, 1990 Sep-Oct, 141(7-8), 827 - 30 Alternative methods of attenuating Salmonella species for potential vaccine use; Wilson DR et al.; Because of their invasive properties, Salmonella species are uniquely suited for use as live oral vaccines, and mutants attenuated in general metabolic functions show promise as vaccine strains . We have identified a Salmonella choleraesuis transposon mutant which is deficient in abilities to attach to, invade or penetrate through animal cells . This mutant is avirulent in mice, yet is able to persist within the liver, spleen and gut-associated lymphoid tissue for periods which may be adequate for induction of secretory, humoral and cell-mediated immunity . This and other strains attenuated in factors specifically required for Salmonella pathogenesis may have potential as vaccine strains. Res Microbiol, 1990 Sep-Oct, 141(7-8), 797 - 805 Stabilization of recombinant avirulent vaccine strains in vivo; Curtiss R 3rd et al.; Salmonella strains attenuated by various mutational alterations and expressing heterologous colonization and virulence antigens specified by cloned genes have begun to be widely used as vaccines for oral immunization to induce protective immunity against the pathogens supplying the genes for the colonization or virulence antigens . Problems associated with plasmid instability and/or poor expression of cloned gene products have frequently been encountered and regulatory agencies are now banning use of antibiotic resistance markers in live attenuated vaccine strains . We have therefore developed a balanced lethal host-vector system in which the chromosome of the attenuated vaccine strain contains a deletion mutation that impose a requirement for diaminopimelic acid (DAP), an essential constituent of the rigid layer of the cell wall of all Gram-negative and some Gram-positive microbes . The plasmid cloning vector contains the wild-type allele for this gene allowing the recombinant avirulent Salmonella to be independent of DAP . Since DAP is not prevalent in nature, especially in the animal host, essentially 100% of the surviving avirulent Salmonella recovered from an immunized animal host still contain the recombinant plasmid and express the foreign colonization or virulence antigen . Occasional loss of the plasmid renders the avirulent Salmonella DAP-requiring, which quickly results in DAPless death with lysis of the bacterium to release its antigenic contents, an occurrence which might further enhance the immune response to the foreign colonization or virulence antigen . We describe below strains of bacteria, recombinant vectors and the methods to make use of this system in a diversity of situations for development of live recombinant avirulent vaccines as well as for other potential applications. Res Microbiol, 1990 Sep-Oct, 141(7-8), 787 - 96 Aromatic-dependent Salmonella as live vaccine presenters of foreign epitopes as inserts in flagellin; Stocker BA; Synthetic oligonucleotides specifying amino acid sequences identified as epitopes of various foreign antigens (cholera toxin subunit B, hepatitis B surface protein and others) have been inserted at an EcoRV-EcoRV deletion site in a cloned Salmonella flagellin gene; the resulting plasmids, when placed in flagellin-negative Escherichia coli or Salmonella sp . strains, caused production of flagellin expressing the epitope . If the chimeric flagellin allowed formation of flagella, the epitope was exposed at the surface of the flagellar filaments . A delta aroA flagellin-negative S . dublin live vaccine strain given plasmids carrying various chimeric flagellin genes was administered to mice, etc . Serum antibody specific for the foreign epitope was in all cases evoked by parenteral administration; oral route administration was effective in the case of two epitopes of hepatitis B surface protein but not effective for several other epitopes . Several i.p . inocula of the live vaccine strain with an insert corresponding to the 15 N-terminal amino acids of the M protein of Streptococcus pyogenes type 5 evoked M-specific antibody with opsonic activity, and the mice were (incompletely) protected against a lethal challenge of S . pyogenes type 5 . The non-virulence of Salmonella sp . strains with complete blocks in the aromatic biosynthesis pathway, even for animals with genetically determined or other defects in host defences, can be completely accounted for by their requirement for p-aminobenzoic acid, since non-leaky pabB mutations caused similar attenuation . Two transposon insertions at aroE caused little or no attenuation, presumably because they did not result in complete block of the relevant step in biosynthesis . The limited growth of delta aroA strains in mouse tissues parallels that which precedes the bacteriostasis caused by addition of a sulphonamide to a growing broth culture of a sulphonamide-sensitive strain; the final cessation of growth in each case presumably results from inability to initiate new protein chains with a formyl-methionine unit when the original folic acid content of the bacteria has been diluted out by residual growth. Mol Immunol, 1990 Sep, 27(9), 859 - 65 Salmonella O antigen-specific oligosaccharide-octyl conjugates activate complement via the alternative pathway at different rates depending on the structure of the O antigen; Grossman N et al.; Artificial Salmonella serogroup B, D or Cl-specific glycolipids were prepared by covalently linking oligosaccharides corresponding to two O-antigen repeating units, obtained by phage enzyme hydrolysis of native O-antigenic polysaccharides, to octyl residues . Sheep erythrocytes coated with the artificial glycolipids were studied for their ability to consume C3, when incubated in C4- deficient guinea pig serum . Salmonella C1 (0-6,7) glycolipid-coated erythrocytes consumed C3 40% more efficiently than Salmonella D (0-9,12) glycolipid-coated erythrocytes, and 10-times more efficiently than Salmonella B (0-4,12) glycolipid-coated erythrocytes . These results resemble C3 consumption by Salmonella C1, D, and B cells and by sheep erythrocytes coated with purified lipopolysaccharides of these O-specificities . The results prove directly that in a particulate system C3 activation via the alternative pathway depends on the structural properties of the O-antigenic side chain . Structures as small as octasaccharides, or as two O-antigenic repeating units, are sufficient for triggering C3 activation, but the magnitude of activation depends on the nature of the monosaccharides . Apparently, neither the core oligosaccharide nor Lipid A of lipopolysaccharide are required for C3 activation via the alternative pathway. Biochim Biophys Acta, 1990 Aug 17, 1035(2), 201 - 5 Altered responses to modulators of guanine nucleotide binding protein activity in endotoxin tolerance; Coffee KA et al.; The effects of cholera toxin or pertussis toxin and nonhydrolyzable GTP analogs on Salmonella enteritidis endotoxin stimulation of iTxB2 and i6-keto-PGF1 alpha synthesis in control and endotoxin tolerant rat peritoneal macrophages were determined . Pretreatment with pertussis toxin alone had no effect on basal macrophage iTxB2 or i6-keto-PGF1 alpha production, but pertussis toxin (0.1, 1.0 and 10 ng/ml) significantly inhibited endotoxin-stimulated iTxB2 and i6-keto-PGF1 alpha synthesis . Pretreatment with cholera toxin, which did not affect basal iTxB2 or i6-keto-PGF1 alpha synthesis, significantly enhanced endotoxin-induced synthesis of iTxB2 and i6-keto-PGF1 alpha . The effects of pertussis and cholera toxin with or without endotoxin were significantly (P less than 0.05) less in macrophages from endotoxin tolerant rats compared to control macrophages . GTP{gamma-S} (100 microM) significantly increased iTxB2 synthesis and significantly augmented endotoxin-stimulated iTxB2 synthesis in control macrophages (P less than 0.05) . However, in macrophages from endotoxin tolerant rats the effect of GTP{gamma-S} on iTxB2 synthesis was significantly less (P less than 0.05) compared to control macrophages . Collectively, these data suggest that: (1) guanine nucleotide binding regulatory proteins mediate endotoxin-stimulated arachidonic acid metabolism in rat peritoneal macrophages; and (2) endotoxin tolerance induces alterations in guanine nucleotide binding protein activity. Nature, 1990 Aug 9, 346(6284), 586 - 9 Structure of Arc repressor in solution: evidence for a family of beta-sheet DNA-binding proteins; Breg JN et al.; The Arc repressor, which is involved in the switch between lysis and lysogeny of Salmonella bacteriophage P22, does not belong to any of the known classes of DNA-binding proteins . Mutagenesis studies show that the DNA-binding region is located in the 15 N-terminal amino-acid residues . We have now determined the three-dimensional structure of the Arc dimer from an extensive set of interproton-distance data obtained from 1H NMR spectroscopy . A priori, intra- and inter-monomer nuclear Overhauser effects (NOEs) cannot be distinguished for a symmetric dimer . But by using the homology with the Escherichia coli Met repressor we could interpret the NOEs unambiguously in an iterative structure refinement procedure . The final structure satisfies a large set of NOE constraints (1,352 for the dimer) . It shows a strongly intertwined dimer, in which residues 8-14 of different monomers form an antiparallel beta-sheet . A model for the Arc repressor-operator complex can account for all available biochemical and genetic data . In this model two Arc dimers bind with their beta-sheet regions in successive major grooves on one side of the DNA helix, similar to the Met repressor interaction . Thus, Arc and Met repressors are members of the same family of proteins, which contain an antiparallel beta-sheet as the DNA-binding motif. Science, 1990 Aug 3, 249(4968), 511 - 7 The Hin invertasome: protein-mediated joining of distant recombination sites at the enhancer; Heichman KA et al.; The Hin protein binds to two cis-acting recombination sites and catalyzes a site-specific DNA inversion reaction that regulates the expression of flagellin genes in Salmonella . In addition to the Hin protein and the two recombination sites that flank the invertible segment, a third cis-acting recombinational enhancer sequence and the Fis protein, which binds to two sites within the enhancer, are required for efficient recombination . Intermediates of this reaction were trapped during DNA strand cleavage and analyzed by gel electrophoresis and electron microscopy in order to determine their structure and composition . The analyses demonstrate that the recombination sites are assembled at the enhancer into a complex nucleo-protein structure (termed the invertasome) with the looping of the three segments of intervening DNA . Antibody studies indicated that Fis physically interacts with Hin and that both proteins are intimately associated with the invertasome . In order to achieve this protein-protein interaction and assemble the invertasome, the substrate DNA must be supercoiled. Vaccine, 1990 Aug, 8(4), 321 - 6 Antibody-secreting cells in the evaluation of the immunogenicity of an oral vaccine; Kantele A; The immune response to different dosage schedules of oral live Salmonella typhi Ty21a vaccines was studied by enumeration of specific antibody-secreting cells (ASC) in the peripheral blood believed to have been stimulated by the vaccine antigen on mucosal surfaces and to be on their way back to those sites for local antibody secretion . Four groups of subjects were vaccinated with either three (3 x S), two (2 x S) or one (1 x S) dose of a suspension-formulated vaccine, or with three doses of vaccine in enteric-coated capsules (3 x E) . The ASC-responses were highest in group 3 x S, followed by 3 x E, 2 x S and 1 x S, in this order . These differences parallel differences in protection from disease as observed in field trails with these regimens . This assay might therefore be useful for presumptive assessment of the protective ability of new vaccines or vaccine regimens . It certainly can be used to measure the immunogenicity of an oral vaccine. J Clin Microbiol, 1990 Aug, 28(8), 1867 - 9 Use of commercially available rapid chloramphenicol acetyltransferase test to detect resistance in Salmonella species; de la Maza L et al.; Chloramphenicol resistance among Salmonella spp . has important public health and clinical implications, especially in areas of the world where these strains are endemic . The availability of rapid and sensitive screening methods for detection of antibiotic resistance is important . Therefore, we tested 33 strains of Salmonella for chloramphenicol acetyltransferase (CAT) activity using two rapid techniques . Evaluation of a 1-h tube method and a 30-min commercial disk procedure demonstrated that they are as accurate as standardized susceptibility techniques . Both the 1-h tube and 30-min disk methods detected CAT enzymatic activity produced by one CAT gene copy per cell. Mutat Res, 1990 Aug, 244(4), 273 - 7 The interaction of methanol, rat-liver S9 and the aromatic amine 2,4-diaminotoluene produces a new mutagenic compound; Cunningham ML et al.; Methanol is a widely used solvent for organic compounds and a human toxicant . In our studies of the metabolism of aromatic amines in the Ames/Salmonella assay, we observed a rapid and quantitative conversion of the mutagenic and carcinogenic aromatic amine 2,4-diaminotoluene (2,4-DAT) to a single product . This product was only produced in the presence of methanol, and not other organic solvents . Isolation of this product showed that it was highly mutagenic in Salmonella TA98 with S9 activation . Characterization of the product of the interaction of methanol and 2,4-DAT indicated that methanol is activated to a reactive intermediate, probably formaldehyde, by the 9000 X g supernatant used in the Ames/Salmonella assay . The formaldehyde subsequently reacts with 2,4-DAT to form the mutagenic product, identified as bis-5,5'(2,4,2',4'-tetraaminotolyl)methane . Results of this study demonstrate that methanol may be an inappropriate solvent for mutation and metabolism studies of aromatic amines and possibly other chemicals, and that solvent-xenobiotic interactions may in some cases lead to the misinterpretation of results. Mutat Res, 1990 Aug, 241(4), 379 - 85 Evaluation of genotoxicity of N-nitrosodibenzylamine in Chinese hamster V79 cells and in Salmonella; Boyes BG et al.; Health concerns have arisen due to the formation of N-nitrosodibenzylamine (NDBzA; CAS No . 5336-53-8) in pork processed in a new type of rubber netting . In view of the potent carcinogenicity of related nitrosamines (e.g . N-nitroso-n-dibutylamine and N-nitrosodiethylamine), NDBzA was evaluated for genotoxicity in vitro in both Chinese hamster V79 cells and in Salmonella . In V79 cells, concentrations up to 25 micrograms/ml were tested with and without activation by rat or hamster hepatocytes . Significant elevation of SCE frequency was see