Ophthalmologica, 1986, 192(3), 154 - 8 Stellate maculopathy due to Salmonella typhi . A case report; Fusco R et al.; A case of typhoid fever complicated by bilateral chorioretinitis and monolateral stellate maculopathy is reported . Clinical findings are discussed. Ann Med Interne (Paris), 1986, 137(2), 115 - 7 {Pathology of the bile ducts in children with homozygous sickle-cell anemia . Apropos of 5 recent cases}; Begue P et al.; Five cases of biliary complications in childhood sickle cell disease are reported . In four cases, the pathology was gall stones causing recurrent abdominal pain in a 10 year old boy, a 13 year old girl and a 2 year old infant, and responsible for a "Salmonella septicaemia" in a 17 year old adolescent . In one case, a biliary cyst was diagnosed at 3 years of age . Four children underwent successful surgery . The complications of gall stones are difficult to distinguish from episodes of vasoocclusive abdominal pain . Ultrasonography is an easy method of detecting gall stones and may be repeated regularly in children over 10 years of age . All the children operated in this series were improved by surgery . Patients with sickle cell disease must be carefully prepared for general anaesthesia with a strict protocol of blood transfusion which is only possible in well equipped centers . Elective surgery is by far the best management as postoperative complications are much less common than after emergency surgery . A review of the literature shows that the general tendency is for surgical intervention as gall stones are a cause of recurrent abdominal pain, cholecystitis and dangerous infective complications in those patients. J Clin Microbiol, 1986 Jan, 23(1), 192 - 4 Salt-induced filamentous growth of a Salmonella strain isolated from blood; Yoshida S et al.; A strain of Salmonella choleraesuis subsp . choleraesuis serovar paratyphi-A isolated from the blood of a febrile patient grew into filaments on a nutrient agar containing various salts, such as NaCl, KCl, MgCl2, NH4Cl, (NH4)2SO4, or (NH4)2HPO4, at concentrations of 50 to 400 mM . The filamentous cells were nonseptate and multinucleate, and they had colony-forming ability . This mutant strain, however, did not show filamentous growth in liquid media which contained the same salts . On nutrient agar containing 20% sucrose but no salts, some of the cells formed large spheroplasts . Both ampicillin treatment and in vivo environment may in part be responsible for the induction of the mutant strain. Bull Soc Pathol Exot Filiales, 1986, 79(1), 22 - 6 {Absence of the antigen H:z66 in 2355 strains of Salmonella typhi from Madagascar and several countries of tropical Africa}; Vieu JF et al.; The presence of the new flagellar antigen H:z66 (Guinee, 1981) was investigated among 2,355 strains of S . typhi isolated from 1981 to 1985 in Madagascar and some countries of tropical Africa: Burundi, Ivory Coast, Gabon, Mauritania, Central African Republic, Rwanda, Senegal, Zaire . A method based on the immobilization of motile strains in soft agar with immunserum anti-H:d, was used to detect strains carrying antigen H:z66 . No African and malagazy strains had antigen H:z66, irrespective to their biovar, phage-type, drug susceptibility and geographical origin . These results were compared with a study of 2,121 indigenous or imported strains of S . typhi isolated in France during the same period . Except 4 strains from patients contaminated in Indonesia, all of them were also devoid of antigen H:z66 . Future research is needed for a complete assessment of the geographical distribution of S . typhi antigen H:z66. Trans R Soc Trop Med Hyg, 1986, 80(5), 748 - 52 Morbidity and mortality in a diarrhoeal diseases hospital in Bangladesh; Islam SS et al.; Records of all patients who were admitted to or who died in Dhaka hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) between July 1980 and 30th June 1981 were reviewed to identify epidemiological characters associated with in-hospital diarrhoeal diseases-related deaths . Information on aetiological agents, age, sex, major complications, nutritional status and level of dehydration were analysed . Over the one-year period, 3251 patients were admitted to the medical wards and 400 died . Children under five made up 72% of patients admitted and 77% of those who died . All patients were cultured for enteric vibrios, Salmonella and Shigella; 25% of the patients had at least one of these organisms . Shigella was most common and was isolated from 13% of the patients and 19% of those who died . Case-fatality rates in patients with Shigella and Vibrio cholerae non-OI (NAG) were significantly higher than other enteric pathogens (V . cholerae OI, Salmonella typhi and mixed) . Case fatality for Vibrio cholerae non-OI was higher than Shigella (25.8% and 17.2%) but the difference was not statistically significant . Among those who died 21% were severely dehydrated and 50% had various complications . Patients with V . cholerae OI were significantly more dehydrated than other groups (P less than 0.05 by chi 2 test) . The patients who died with Shigella were significantly more malnourished and had more frequent associated complications than other non-Shigella diarrhoea patients (P less than 0.01 by chi 2 test) . Overall our observations indicate that Shigella and Vibrio cholerae non-OI are associated with unusually high case fatality.(ABSTRACT TRUNCATED AT 250 WORDS) IARC Sci Publ, 1986, (77), 393 - 7 Genotoxicity of hexachlorobenzene and other chlorinated benzenes; Brusick DJ; Hexachlorobenzene (HCB) and other chlorinated benzenes have had only limited mutagenicity evaluation but tests have shown a general lack of evidence for mutagenicity . Bacterial reverse mutation studies have been typically negative and only a few studies on cultured mammalian cells have been published . Recent reports indicate that HCB does not induce sister chromatid exchange or DNA-strand breakage in vitro . A single report of HCB-induced reverse mutation in yeast is suspect due to the failure to establish either dose-response effects or an acceptable level of statistical significance . In-vivo data are limited primarily to dominant lethal studies in rats and some in-vivo alkaline elution results . Both types of tests revealed no genetic activity for HCB . A number of chlorine-substituted nitrobenzenes are positive in the Ames Salmonella reverse mutation assay, but when tested in eukaryotic cell assays, the results are generally negative . Ortho-, meta- and para-dichlorobenzenes are apparently mutagenic in Aspergillus nidulans, and para-dichlorobenzene has been reported to induce mitotic abnormalities in plant cells . Unscheduled DNA synthesis studies carried out with dichlorobenzenes proved negative . Monochlorobenzene failed to actively induce sister chromatid exchange in a human cell line . The only human data that have been reported for chlorinated benzenes involved accidental exposure of 26 people to ortho-dichlorobenzene vapours . Analysis of lymphocytes from this cohort suggested an increase in chromosome breakage. Microbiol Immunol, 1986, 30(12), 1213 - 24 Invasiveness of Salmonella typhi strains in HeLa S3 monolayer cells; Yabuuchi E et al.; The internalization and intracellular multiplication, i.e., the invasiveness, of Salmonella typhi strains recently isolated from typhoid fever patients were confirmed in HeLa cell monolayers . When stained with Giemsa solution, intracellular bacteria were 0.6 X 1.2 micron in size and stained purple, whereas extracellular bacteria associated or not with the HeLa cell surface were 1.0 X 3.0 micron and stained deep blue . Strain GIFU 10007 was internalized into 23% of the HeLa cells within 10 min after inoculation . About 90% of the HeLa cells were infected after 24 hr incubation in kanamycin (KM)-containing medium . Intracellular multiplication of the challenge organism was verified by a large number of intracellular bacteria after 24 hr incubation in KM-containing medium by both light-microscopy of the Giemsa stained preparation and viable counts of intracellular bacteria . The viable counts of strain 10007 showed an increase of more than 40-fold within 24 hr after inoculation, whereas in the four other less or non-infective strains, recovery of viable bacteria was poor or nil . Strains which were highly invasive usually failed to show strong adhesion . The contribution of Vi antigen to the internalization of challenge organisms was not proved . Infective strains, when killed by formalin were still adhesive, but were not internalized . The same strains, when killed by boiling, were neither adhesive nor internalized . From these findings it was concluded that the internalization and multiplication of infective S . typhi strains in cultured HeLa cells should be regarded as an invasion rather than phagocytosis by host cells, and such invasiveness could be an indicator to estimate the virulence of S . typhi strains. Microbiol Immunol, 1986, 30(12), 1225 - 37 Cytopathogenic effect of Salmonella typhi GIFU 10007 on M cells of murine ileal Peyer's patches in ligated ileal loops: an ultrastructural study; Kohbata S et al.; An electron microscopic study revealed that, within 30 min after inoculation into the ligated ileal loop of anesthetized mice, cells of Salmonella typhi GIFU 10007 adhered to the M cell surface of Peyer's patch lymphoid follicle epithelium, and induced almost complete destruction of M cells . The M cell cytoplasms were pinched off and extruded from the epithelial lining into the luminal space together with the lymphoid cells primarily enfolded into the corresponding M cells . When two or more M cells were destroyed, a large defect in the epithelial lining was apparent, and a number of bacteria appeared near the basal lamina of the epithelial lining . These findings suggest, as far as anesthetized murine ileal loops and strain 10007 are concerned, that ileal M cells are the target cell at an early stage of S . typhi infection and the infection may further progress to deeper tissues and to the general circulation. Ann Rech Vet, 1986, 17(4), 387 - 93 {Experimental infection with Salmonella abortus ovis in rams}; Sanchis R et al.; The susceptibility of rams to experimental challenge with Salmonella abortus ovis was investigated by subcutaneous, conjunctival or preputial administration of 1 X 10(10) viable salmonella to 3 groups of 6 adult Prealpes rams . Slaughter and autopsy of 15 rams were made 83 days after challenge . Each of the 3 remaining rams was introduced in 3 groups of 6 salmonellosis-free ewes . The subcutaneous injection caused a significant hyperthermia, a rapid increase in antibody titers without detectable genital excretion of salmonella . The conjunctival or preputial challenge caused a significant serological response without fever; S . abortus ovis was isolated from samples taken 1 to 13 days after challenge only in rams challenged by the preputial route . No salmonella was isolated from organs of the 15 slaughtered rams . Ewes made pregnant by the 3 remaining rams showed no signs of infection . In our experimental conditions, a genital colonization was not observed; a passive genital carriage of S . abortus ovis was shown to be possible; its hypothetical epidemiological role was discussed. Braz J Med Biol Res, 1986, 19(1), 19 - 25 Mutagenicity of nifurtimox and benznidazole in the Salmonella/microsome assay; Ferreira RC et al.; The genetic activities of two widely used anti-Trypanosoma cruzi drugs, nifurtimox and benznidazole, were investigated . The Salmonella mutagenicity (Ames) test was used to evaluate the mutagenic activity of both drugs . Nifurtimox and benznidazole preferentially induced backward mutations in the base substitution mutagen indicator strain TA100 . The observed mutation rates for both drugs were linear over a wide concentration range . Maximum mutagenic activity was obtained at 35 and 100 micrograms per plate for nifurtimox and benznidazole, respectively . No increase in the mutagenic activity of either drug was observed in the presence of rat liver microsomal extracts . Survival experiments revealed that nifurtimox was at least four times more toxic than benznidazole for the Salmonella indicator strain. Trans R Soc Trop Med Hyg, 1986, 80(2), 323 - 6 Curative properties of muramyl dipeptide in experimental Naegleria meningoencephalitis; Ferrante A et al.; Naegleria fowleri is a free-living amoeba which causes a fatal meningoencephalitis in man . Mice injected with the immunostimulant MDP or an attenuated 11RX strain of Salmonella enteritidis showed some resistance to an intranasal challenge with N . fowleri . In addition it was observed that some of the mice infected with N . fowleri and showing symptoms of naegleria meningoencephalitis, given a single injection of MDP were cured of this disease . Our findings suggest that the use of immunostimulants could be a new approach in the quest for therapeutic agents for this disease. Trans R Soc Trop Med Hyg, 1986, 80(2), 317 - 22 The serum bactericidal and opsonizing defect in sickle cell anaemia: restoration of activity by control serum; Luo NP et al.; Thirty-eight homozygous sickler sera were compared with a large pool of serum from healthy African non-sicklers with regard to bactericidal and phagocytic indices . One third of the sera showed reduced bactericidal activity against Salmonella enteritidis which was restored by the addition of 4% control serum; control serum provided both heat-labile (HL) and absorbable (ABS) serum factors . 76% of test sera showed greatly defective opsonization as indicated by ingestion by normal human neutrophils . Activity was not readily restored by the addition of control serum which provided only HL factors . Intracellular survival was increased when bacteria were ingested from sickler serum; activity was readily restored by control serum which provided both HL and ABS factors . In the presence of both serum and neutrophils 84% of test sera permitted increased bacterial survival; the defect was not readily reversed by the addition of control serum which provided both HL and ABS factors. Environ Mutagen, 1986, 8(5), 693 - 704 Environmental tobacco smoke: comparative characterization by mutagenicity assays of sidestream and mainstream cigarette smoke; Lofroth G et al.; Mainstream cigarette smoke particles were collected by means of a smoking machine, and sidestream particles were collected from the room in which the smoking took place . The particles were extracted by sonication with acetone, and the extracts were solvent-exchanged to dimethyl sulfoxide . The samples were tested for mutagenicity in the Ames Salmonella/microsome assay . The mainstream extract is preferentially mutagenic in the presence of S9, with about 30,000 revertants/cigarette in TA98, but has little or no activity in its absence . The sidestream extract is also mutagenic in the presence of S9 with TA98, and this activity is mainly due to basic compounds . Sidestream smoke is also significantly mutagenic in the absence of S9 in the strain TA100 as well as in TA97 and TA104 . This "direct" activity is due to components that are labile . The response of sidestream particles is 10,000-20,000 revertants/cigarette in TA98 + S9 and TA100-S9 when the collection is performed in a room where the particle concentration is modulated by deposition to surfaces . Sidestream particles collected on glass fiber filter and by electrostatic precipitation (ESP) with a commercial air cleaning device gave essentially the same mutagenic response, showing that ESP sampling may be an alternative to filter sampling for environmental tobacco smoke (ETS) in indoor environments . ESP sampling in children's rooms in smoking and nonsmoking homes showed that 5-10% of the tobacco smoke emitted in the smoking homes entered the child's room, demonstrating that diffusion of pollutants is faster than ventilation in modern buildings with low ventilation rates. Environ Mutagen, 1986, 8(4), 631 - 41 Target sequences for mutagenesis in Salmonella histidine-requiring mutants; Hartman PE et al.; Nucleotide target sequences involved in reversion to the wild type phenotype are diagrammed for Salmonella frameshift histidine-requiring mutants hisD3052, hisD3018, hisD6610, and hisD6580 and for base-substitution mutants hisG46 and hisG428 . Frameshift strain hisC3076 probably reverts by nucleotide changes similar to those that occur during reversion of hisD3018 and hisD6610 . Multiple modes of reversion characterize each strain . Each strain also has a particularly diagnostic mutagen-susceptible sequence . These highly mutagen-susceptible stretches are the hisD3052 GCGCGCGC sequence, the hisD6610 CCCCCC sequence, the hisD6580 AAAAA sequence, and the A/T containing codon of hisG428 and G/C containing codon of hisG46, respectively . Between them, hisG46 and hisG428 are reverted by all of the six possible base substitution transition and transversion mutations. Tierarztl Prax, 1986, 14(1), 51 - 4 {Experiences with local administration of herd-specific vaccines}; Bauer K; The results of oral vaccination of 388 calves with herd-specific vaccines against E . coli are described . Innocuity was optimal, whereas the potency was estimated not as efficient as parenteral vaccination of the dam (in 22% of the cases), i.e., transient diseases in vaccinated calves occurred there . Further the results of intranasal vaccination of 496 cattle against salmonellosis are reported . Salmonella excretion in the faeces was stopped within 1-3 weeks post vaccination in 75% of the herds . In one case it took 3 months to reach this effect . A few permanent excretor cattle remained in two other cases. Biomed Pharmacother, 1986, 40(1), 6 - 10 Effects of splenectomy on the retention of Salmonella enteritidis and on the hemopoietic response to Salmonella infection; Kirikae T et al.; Salmonella infection induces a marked increase in the splenic granulopoiesis, but causes a reduction in hemopoiesis in the bone marrow . In this study, effects of Salmonella enteritidis infection on hemopoietic stem cells were examined in splenectomized (SX-) mice . Splenectomy emphasized hemopoietic damage in the bone marrow caused by Salmonella infection . Total nucleated cells, pluripotent stem cells (CFUs) and granulocyte-macrophage progenitor cells (GM-CFC) in the bone marrow of SX-mice all decreased markedly compared with sham-splenectomized (NX-) mice, and the recovery from the decline was also delayed . Thus, neither enhancement of the granulopoiesis nor granulopoietic recovery in the bone marrow was observed to compensate the granulopoietic response in the spleen . Splenectomy also resulted in a longlasting retention of Salmonella in the liver . The observations indicate that the spleen is the major organ to respond to bacterial invasion in regard to enhanced granulopoiesis and hence enhanced bacterial clearance. Environ Mutagen, 1986, 8 Suppl 7, 1 - 119 Salmonella mutagenicity tests: II . Results from the testing of 270 chemicals; Mortelmans K et al.; This publication includes data of Salmonella mutagenicity results on 270 coded chemicals, encompassing 329 tests performed by three laboratories under contract to the National Toxicology Program (NTP) . The preincubation modification of the Salmonella/mammalian microsome assay was used to test chemicals in up to five Salmonella strains in the presence and absence of rat and hamster liver S-9 . With a few exceptions, inter- and intralaboratory reproducibility was good. Agents Actions, 1986 Jan, 17(3-4), 368 - 70 In vivo inhibition of plasma protein leakage and Salmonella enteritidis-induced mortality in the rat by a specific paf-acether antagonist: BN 52021; Etienne A et al.; The effects of BN 52021, a new specific paf-acether receptor antagonist and the total Ginkgo Biloba extract (GBE 761) from which this product was isolated, were studied in the rat on paf-acether-induced permeability and cell number changes and on endotoxin-induced lethality . Their activities were compared to those of cyclooxygenase, 5-lipoxygenase and phospholipase A2 inhibitors . BN 52021 given s.c . or orally exerted a dose-related inhibition of paf-acether deleterious effects as well as of endotoxin lethality whereas the other drugs tested were poorly effective . These results strongly suggest paf-acether involvement in endotoxic and septic shock. Arzneimittelforschung, 1986, 36(1), 17 - 9 In vitro studies of antidermatophytic activity of juliflorine and its screening as carcinogen in Salmonella/microsome test system; Khursheed AK et al.; Juliflorine, an alkaloid from Prosopis juliflora, was tested for its antifungal activity against the freshly isolated cultures of dermatophytic fungi and its inhibitory effect was compared with that of griseofulvin . The results indicated that the minimum inhibitory concentration (MIC) of juliflorine against Trichophyton rubrum, Trichophyton violaceum, Trichophyton mentagrophytes, Trichophyton tonsurans, Trichophyton megninii, Trichophyton gallinae, Microsporum canis, Microsporum nanum, Microsporum ferrugineum and Epidermophyton floccosum was 1.5 micrograms/ml, whereas that of griseofulvin was 0.1-0.5 microgram/ml . MIC of juliflorine for Candida albicans was 0.05 mg/ml . The alkaloid was also subjected to screening for carcinogenicity in the Ames test (salmonella/microsome test system) . The results indicated that the compound in the recommended concentrations did not exhibit positive mutagenic reaction, as compared to a strong positive reaction by ethyl methane sulfonate based on his- ----his+ revertants. Rev Infect Dis, 1986 Jan-Feb, 8(1), 31 - 41 Salmonella focal intracranial infections: review of the world literature (1884-1984) and report of an unusual case; Rodriguez RE et al.; Focal intracranial infections are unusual manifestations of salmonellosis . Forty-three such infections have been reported in the world literature . The clinical data for 34 well-documented cases are reviewed . Eleven patients had brain abscess, 19 had subdural empyema, three had epidural abscess, and one had both subdural empyema and brain abscess . Brain abscess occurred more often in adults; in contrast, subdural empyema presented more often in children . Fever, signs and symptoms of increased intracranial pressure, change in mental status, seizures, and focal neurologic deficits were the commonest clinical features . Salmonella serotypes typhi, typhimurium, and enteritidis occurred most frequently . The precipitating factors of these infections included meningitis, trauma, and intracranial hematoma . Surgical drainage combined with systemic antibiotic therapy resulted in the recovery of 21 of 25 patients . A case of embryonal carcinoma plus seminoma of the testis with brain metastases complicated by a salmonella brain abscess is also reported . This is the first report in the world literature of a focal salmonella infection in a neoplastic lesion within the central nervous system. Food Chem Toxicol, 1986 Jan, 24(1), 13 - 5 Relation of nitrite concentration to mutagen formation in soy sauce; Nagahara A et al.; When soy sauce was mixed with nitrite solutions at pH 1.0 and 3.0, only mixtures containing nitrite concentrations above 250 ppm were mutagenic in the Salmonella/mammalian microsome test . In buffered aqueous solution (pH 3) the mutagen precursor, (-)-(1S,3S)-1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid {(1S,3S)-MTCA} and its stereoisomer ( - )-(1R,3S)-MTCA reacted with 10 ppm or more of sodium nitrite; but at least 250 ppm nitrite was required for them to react in soy sauce (pH 3) . Similarly, another mutagen precursor, tyramine, did not react even with 2300 ppm nitrite in soy sauce (pH 1), although pure tyramine in aqueous solution (pH 1) reacted with as little as 50 ppm nitrite . Nitrite concentration in human saliva and gastric juice does not generally exceed 50 ppm . Therefore, the most probable source of mutagens--nitrosation of MTCAs and tyramine--is likely to be very restricted in vivo and soy sauce is unlikely to be significantly mutagenic. Tijdschr Diergeneeskd, 1986 Jan 1, 111(1), 9 - 13 {Resistance to antibiotics in Salmonella}; van Leeuwen WJ et al.; Approximately 20,000 strains of Salmonella were screened annually for resistance to tetracycline, chloramphenicol, kanamycin and ampicillin since 1959, and also to trimethoprim since 1978 . Tetracycline-resistant strains increased in human subjects and pigs from 1961 . After the ban on incorporation of tetracycline in animal feeds for nutritive purposes in 1974, the proportion of tetracycline-resistant strains in pigs and human subjects decreased . In veal calves, the number of strains of S . typhimurium and S . dublin resistant to multiple drugs increased from 1972 . Strains resistant to multiple antibiotics in man were mainly isolated from adoptive children from Indonesia . No further spread of these strains was observed . So far, strains similar to those in calves resistant to multiple drugs were only incidentally isolated from human patients. Pediatr Infect Dis, 1986 Jan-Feb, 5(1 Suppl), S91 - 100 Classical bacterial diarrhea: perspectives and update--Salmonella, Shigella, Escherichia coli, Aeromonas and Plesiomonas; Rennels MB et al.; Impressive advancements in our understanding of the mechanisms of diarrhea production and of the epidemiologic importance of these "classical" bacterial enteropathogens have been accomplished, but many areas are in need of further exploration . The recent development of gene probes and enzyme-linked immunosorbent assays for the identification of EPEC, ETEC and EIEC will enhance immeasurably the ability to carry out large scale epidemiologic studies which are still needed to clarify the global importance of these pathogens in infantile diarrhea . For some of these organisms pathogenic mechanisms remain incompletely understood and the role of antibiotics is not well-established . The delineation of virulence factors, immunity and the construction of attenuated strains through DNA recombination technology are bringing the worthy goal of prevention through vaccination into view . These advances should not, however, detract attention from the primary reason that these bacteria continue to be a major cause of childhood morbidity and mortality in the developing world, which is lack of adequate sanitation . Efforts to provide clean water, safe waste disposal and hygiene education need to proceed in conjunction with development of vaccines. Mutat Res, 1986 Jan-Feb, 169(1-2), 41 - 6 Genotoxicity of 'shamma', a chewing material suspected of causing oral cancer in Saudi Arabia; Hannan MA et al.; 'Shamma', also known as Yemeni snuff, is frequently used as a chewing material in Yemen and some parts of Saudi Arabia . Preliminary clinical observations indicated that long-term users of 'shamma' may develop oral cancer . A battery of in vitro bioassays were, therefore, used to test genotoxicity of this substance . The test systems included the histidine reversion assay in Ames' Salmonella strains, induction of aberrant colonies and tryptophan gene conversion in the D7 diploid strain of Saccharomyces cerevisiae, and oncogenic transformation of C3H mouse embryo 10T1/2 cells . Data indicated that direct-acting mutagen(s) were present in a chloroform extract of the powdered 'shamma' resulting in positive effects in all of the test systems used . Using high-performance liquid chromatography (HPLC), three major fractions were separated from the extract, of which two were found to be mutagenic. Mutat Res, 1986 Jan-Feb, 169(1-2), 23 - 7 Bacterial mutagenicity of the tranquilizing constituents of Valerianaceae roots; von der Hude W et al.; The valepotriates valtrate/isovaltrate and dihydrovaltrate are considered to be the main tranquilizing constituents of drugs derived from the roots of several Valerianaceae . The decomposition products of valtrate and isovaltrate include the metabolites baldrinal and homobaldrinal, respectively, whereas the decomposition products of dihydrovaltrate do not include baldrinal-like metabolites . Purified valtrate/isovaltrate, dihydrovaltrate, baldrinal and homobaldrinal were investigated for their genotoxic activity in the Salmonella/microsome test and the SOS-chromotest . The valepotriates developed mutagenic activity in these test systems only in the presence of S9 mix, whereas both baldrinals showed mutagenic effects in both tests with and without metabolic activation. Mutat Res, 1986 Jan-Feb, 169(1-2), 11 - 6 Study of the amniotic fluid from smokers and non-smokers in the Ames test; Rivrud GN et al.; Amniotic fluid from smokers and non-smokers was tested by the Salmonella/mammalian microsome test . Concentrated amniotic fluid from heavy smokers at term showed an increase in the number of revertants with increasing exposure to tar . However, some of the non-smokers had a higher number of revertants than the smokers . No significant differences were found between second-trimester samples from smokers and non-smokers, but the limited volumes available at this stage of pregnancy may be a source of error. J Clin Microbiol, 1986 Jan, 23(1), 205 - 6 Spurious sulfamethoxazole-trimethoprim resistance of Salmonella typhi; Escamilla J et al.; Several studies have identified thymidine excess in susceptibility test media as the cause of spurious resistance of various bacteria to sulfamethoxazole-trimethoprim . We document the phenomenon in Salmonella typhi and Salmonella paratyphi-A and demonstrate its occurrence in 3 of 17 (18%) lots of Mueller-Hinton agars now in use in major medical laboratories in Lima, Peru . The findings are particularly significant because sulfamethoxazole-trimethoprim is an important alternative to chloramphenicol or ampicillin for the treatment of typhoid and paratyphoid fevers. J Immunol, 1986 Jan, 136(2), 569 - 73 Effects of bacterial lipopolysaccharide on the binding of lymphocytes to endothelial cell monolayers; Yu CL et al.; Preincubation of human umbilical vein endothelial cell (EC) monolayers with 1 ng to 10 micrograms/ml lipopolysaccharide (LPS) increased the binding of T lymphocytes to EC . The effect was maximal at LPS concentrations of 0.1 to 10 micrograms/ml, and occurred with LPS derived from Escherichia coli (serotypes 0111:B4 and 0127:B8), Shigella flexneri (serotype 2a), Serratia marcescens (serotype 0:3), and Yersinia entercolitica (serotype 0:3) . The increased binding appeared to be mediated primarily through an action on EC; preincubation of T cells rather than EC with LPS did not lead to enhanced binding . The onset of enhanced binding was very rapid, being observed after 2 to 3 min of preincubation and becoming maximal after 1 hr . EC were unresponsive to LPS after fixation with 2% paraformaldehyde-L-lysine-periodate and also when the LPS was incubated with EC at 4 degrees C . Enhanced binding was seen with lipid A and with LPS from Salmonella minnesota Re 595 (mainly lipid A) and was abolished by conjugation with polymyxin B . The observed increase in the binding of lymphocytes to EC exposed to LPS suggests that the lymphocytopenia induced by endotoxemia may result from augmentation of the adherence of lymphocytes to altered endothelium. Mutagenesis, 1986 Jan, 1(1), 3 - 16 The prospects for a simplified and internationally harmonized approach to the detection of possible human carcinogens and mutagens; Ashby J; It is proposed that the many sets of Regulatory Guidelines for the assessment of chemical carcinogenicity and mutagenicity should be simplified and harmonized in light of current experimental data . Data are discussed which illustrate that an absolute distinction would be drawn between assays conducted in vitro from those in vivo, and that the genotoxicity of a chemical can be adequately defined using a combination of the Salmonella mutation assay and one for the assessment of chromosome aberrations in vitro . It is specifically recommended that once a chemical has shown a clear positive response in vitro, further short-term assays should be conducted in vivo; this avoids considering the 'weight of evidence' of in vitro data, the dangers of which are illustrated . It has now been unequivocally established that not all in vitro genotoxins prove carcinogenic to mammals . It is therefore recommended that all new in vitro genotoxins should be assessed in vivo using the mouse bone marrow micronucleus assay, and if a negative response is observed, a liver genotoxicity test . At present an assay for the induction of unscheduled DNA synthesis (UDS) in the liver is the most well developed for this purpose . Current data indicate that an in vitro genotoxin found to be inactive in these two in vivo assays will be neither carcinogenic nor mutagenic to the germ cells of mammals . Equally, genotoxicity produced in mammals indicates a carcinogenic and mutagenic potential which can usually only be countered by appropriate chronic bioassays . The use of short-term in vivo assays in this critical role requires attention to the selection of appropriate dose-levels and routes of exposure - these issues are discussed . The above testing strategy will not detect certain animal carcinogens, some of which are specifically discussed . These carcinogens have been variously referred to in the literature as epigenetic/non-genotoxic/hormonal/toxic/ambiguous or ambivalent carcinogens . It is suggested that they present a minor potential hazard to man when compared with that of genotoxic carcinogens and that their short-term detection can only be achieved by the development of new whole mammal assays employing non-genetic endpoints . This is in contrast to the present tendency to employ additional genotoxicity assays for their detection in the unjustified belief that they possess an exquisite specificity of genotoxic action . This article represents a personal view, but the testing strategy proposed is based to a large extent on the original three-tier approach of Bridges.(ABSTRACT TRUNCATED AT 400 WORDS) Mutagenesis, 1986 Jan, 1(1), 45 - 8 Activation of benzo{a}pyrene and aflatoxin B1 to mutagenic chemical species by microsomal preparations from rat liver and small intestine in relation to microsomal epoxide hydrolase; Walters JM et al.; Rat small intestinal microsomes have been compared with liver preparations for their ability to activate promutagens using the Salmonella mutagenicity assay . Induced levels of arylhydrocarbon hydroxylase and cytochrome P-450 in intestinal microsomes are significantly lower than the corresponding amounts in liver microsomes . Greater activation of benzo{a}pyrene (BP) by liver extracts would thus be expected . Although this was observed at greater than 1 microgram BP/plate, at lower doses comparatively high levels of activation were obtained with intestinal microsomes . This could be due to preferential formation of the mutagenic 4,5-oxide with intestinal microsomes, as opposed to the putative major active metabolite, the 7,8-diol-9,10-epoxide . Microsomal epoxide hydrolase inactivates the K-region epoxide by forming the corresponding dihydro-diol . Differences in the levels of these metabolites may thus be a result of higher activity of the enzyme in liver extracts . This hypothesis has been studied using the epoxide hydrolase inhibitor, 1,2-epoxy-3,3,3-trichloropropylene oxide (TCPO) . Enzyme activity has been measured using {3H}-BP-4,5-oxide as substrate . Since aflatoxin B1 (AFB) may also be activated via analogous epoxide intermediates, the effects of TCPO on activation of AFB were also investigated . Intestinal microsomal epoxide hydrolase activities were significantly lower than those in liver preparations obtained from animals pre-treated with enzyme inducers . Enzyme activity and promutagen activation ability of intestinal microsomes, respectively, were less susceptible to and not inhibited by TCPO . However, TCPO strongly inhibited microsomal epoxide hydrolase activity and activation of BP and AFB due to liver microsomes.(ABSTRACT TRUNCATED AT 250 WORDS) Environ Mutagen, 1986, 8(6), 839 - 47 Influence of mouse liver stored vitamin A on the induction of mutations (Ames tests) and SCE of bone marrow cells by aflatoxin B1, benzo(a)pyrene, or cyclophosphamide; Qin S et al.; Male mice (C57BL/6J) at 2 weeks of age were divided into two groups and maintained on a vitamin A-deficient or vitamin A-(retinyl acetate) supplemented diet . After 8 weeks, the average liver vitamin A concentration of mice fed on vitamin A-deficient or -supplemented diet was 36 +/- 7 micrograms/g vs 287 +/- 22 micrograms/g, respectively . Uninduced liver S9 fractions were prepared from both groups of mice and used to activate (with cofactors) the precarcinogens aflatoxin B1 (AFB), cyclophosphamide (CPP), dimethylbenz(a)anthracene (DMBA), and benzo(a)pyrene (BP) in the Salmonella mutagenicity assay . S9 fraction prepared from both groups of mice failed to activate CPP to metabolites mutagenic in tester strains TA100 and TA1535 or to activate DMBA to metabolites mutagenic in TA100, but effectively activated AFB and BP to metabolites mutagenic in TA98 . Comparison of activation activities of S9 prepared from liver of mice fed a high or low level of vitamin A was made with T98 treated with AFB or BP using three doses of S9 (50, 100, and 200 microliters/plate) . S9 fractions from mice with a high liver vitamin A level were consistently less potent than S9 fractions from mice with a low liver vitamin A level in activating AFB to its mutagenic metabolites . This effect was not observed in BP-treated plates . Administration of AFB to groups of mice with a high liver vitamin A level induced significantly less SCE in bone marrow cells than did administration of AFB to mice with a low liver vitamin A level . This differential sensitivity was not observed when the two groups of mice were treated with either BP or CPP . The possible relationship between vitamin A levels in vivo and mutagenesis or carcinogenesis are discussed briefly. Acta Biochim Pol, 1986, 33(2), 133 - 7 Regulation of the cysB gene expression in Escherichia coli; Bielinska A et al.; It was found by Northern-type hybridization that the amount of RNA, the transcription of which begins at the cysB regulatory gene promoter, is significantly reduced after cysB gene introduction into Escherichia coli on multicopy plasmid . This result indicates that cysB protein inhibits the transcription of its own gene . O-acetyl-L-serine, an internal inducer of E . coli and Salmonella typhimurin cysteine regulons, has no effect on cysB gene expression. Mikrobiyol Bul, 1986 Jan, 20(1), 14 - 24 {Comparison of the Gruber-Widal and ELISA technics used to study Salmonella typhi and Salmonella paratyphi infections in patients}; Ayyildiz A et al.; In this study, antibody levels were determined against the agents of typhoid and paratyphoid fever in 168 patient's sera and 40 healthy control sera by Gruber-Widal and ELISA techniques . We compared the results of these two techniques, and discussed . The needed antigens for both techniques were prepared from the local strains of the agents of these infections which were isolated in our laboratory . The widal's tube agglutination test was carried out by classical method, and the ELISA technique was done by the method of Woller et al . As a result, we found that the titers obtained by ELISA were as 4-6 times higher as than those of Widal's . Additionally nonspecific reactions were less seen in ELISA than in Widal. Hum Toxicol, 1986 Jan, 5(1), 21 - 6 Interindividual differences in the activation of two hepatic carcinogens to mutagens by human liver; Harries GC et al.; The possibility that the presence of malignant disease can influence the metabolic activation of two carcinogens, 2-acetylaminofluorene and aflatoxin B1, has been investigated in a group of patients with secondary carcinoma of the liver . Mutagenic activation by subcellular fractions from biopsy samples from the patients was determined in the Ames/Salmonella test and the results compared with those obtained from a group of control patients . No significant differences were observed between the groups of patients in their ability to activate the two compounds to mutagenic metabolites . A tenfold range in ability to activate aflatoxin B1 was observed whereas only a threefold range was obtained with 2-acetylaminofluorene . Human liver activates aflatoxin B1 approximately 100 times more efficiently than 2-acetylaminofluorene, a proven carcinogen in many species . This raises the question of the true risk to man from hepatocarcinogenicity from aflatoxin B1. J Mol Evol, 1986, 24(1-2), 61 - 71 In vitro expression of two proteins from overlapping reading frames in a eukaryotic DNA sequence; Jankowski JM et al.; The in vitro expression of two distinct proteins from overlapping reading frames in a sequence of rainbow trout genomic DNA has been demonstrated . In vitro transcription of DNA sequences, cloned in a plasmid under the control of Salmonella phage 6 polymerase promoter, led to the synthesis of two distinct and functional mRNAs corresponding to the protamine mRNA and also to another overlapping mRNA, termed Y . These mRNAs were translated in an mRNA-dependent rabbit reticulocyte lysate cell free system which synthesized the corresponding protein products . Similarities between the synthesized Pro-rich protein Y and three proline-rich proteins, the human salivary Pro-rich protein, the avian sarcoma virus protein P19 and the myc oncogene product, were evident and the significance of these findings is discussed . A synthetic oligonucleotide which is complementary to a sequence corresponding to a region of the Y protein mRNA, but upstream (5') of the transcribed protamine mRNA, hybridized faintly and only to trout brain RNA . However, more sensitive primer extension studies utilizing the Y-specific oligonucleotide detected several Y-related mRNAs in trout brain. Diagn Immunol, 1986, 4(2), 107 - 11 Abnormal B-cell response to T-cell-independent polyclonal B-cell activators in homosexuals presenting persistent generalized lymph node enlargement and HTLV-III antibodies; Kekow J et al.; B-cell functions were investigated in a well-defined high-risk group for the development of AIDS/AIDS-related complex (ARC) . Stimulation of mononuclear cells (MNC) with T-cell-independent polyclonal B-cell activators failed to increase high spontaneous IgG levels observed in vivo and in vitro . The secretion of IgM following stimulation with Klebsiella M (Klebs M) or Salmonella (Salm) membrane preparation increased by a factor of 4 to 6 and thus ranged between the results of the control group and those of AIDS/ARC patients; the response to a T-cell-independent B-cell mitogen, Staphylococcus aureus Cowan I (SAC), showed profound abnormalities as well in this group . This indicates that functional B-cell abnormalities can be seen in addition to T-cell dysfunctions in patients at increased risk for the development of AIDS/ARC. Biochem Cell Biol, 1986 Jan, 64(1), 21 - 8 Structure of the O-chain polysaccharide of the phenol-phase soluble lipopolysaccharide of Escherichia coli 0:157:H7; Perry MB et al.; The phenol-phase soluble lipopolysaccharide isolated from Escherichia coli 0:157 by the hot phenol-water extraction procedure was shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, periodate oxidation, methylation, and 13C and 1H nuclear magnetic resonance studies to be an unbranched linear polysaccharide with a tetrasaccharide repeating unit having the structure: (formula; see text) The serological cross-reactivity of E . coli 0:157 with Brucella abortus, Yersinia enterocolitica (serotype 0:9), group N Salmonella, and some other E . coli species can be related immunochemically to the presence of 1,2-glycosylated N-acylated 4-amino-4, 6-dideoxy-alpha-D-mannopyranosyl residues in the O-chains of their respective lipopolysaccharides. J Gen Microbiol, 1986 Jan, 132 ( Pt 1), 83 - 9 Behaviour of temperate phage Mu in Salmonella typhi; Soberon M et al.; We have developed a convenient system for genetic analysis of Salmonella typhi exploiting the properties of the mutator phage Mu . In spite of the fact that wild-type Salmonella typhi strains do not allow Mu to form plaques on them, we have shown that these strains are actually sensitive to the phage . It proved possible to use Mu to induce mutations and to promote intra- and interspecific genetic transfer, without having to introduce the phage into the bacteria by means other than infection . Furthermore, we isolated Salmonella typhi derivatives on which Mu formed plaques, and studied the behaviour of Mu in these and wild-type strains. J Gen Microbiol, 1986 Jan, 132 ( Pt 1), 97 - 102 The fatty acid content of the Bordetella pertussis endotoxin; Starkloff A et al.; The fatty acid content of Bordetella pertussis endotoxin has been estimated by several methods . Expressed as 3-hydroxytetradecanoic acid, it was 0.74 mumol (mg lyophilized material)-1, 0.38 mumol being ester-bound, and 0.32 mumol in amide linkage . Reported molar ratios of ester-bound to amide-bound fatty acids in endotoxins of various bacterial species range from 2.4 to 2 in B . pertussis, to 5 to 2 in Salmonella minnesota; according to these figures large differences must exist in the degree of substitution, and the substitution pattern of the glucosaminyl-beta-1,6-glucosamine unit present in the hydrophobic region of endotoxins . When fatty acids, released by acid and alkaline hydrolyses of the B . pertussis endotoxin, were extracted into chloroform, unidentified chromogenic substances appearing in the extract interfered with their colorimetric estimation; no interference was observed when hexane was used instead of chloroform. Dev Toxicol Environ Sci, 1986, 13, 253 - 70 Dinitro derivatives of pyrene and fluoranthene in diesel emission particulates and their tumorigenicity in mice and rats; Tokiwa H et al.; A number of mutagens/carcinogens in diesel emission particulates are produced and distributed into the atmosphere . On the basis of the results of chemical analysis, it was found that most of the mutagenicity in diesel particulate extracts is due to super-mutagens such as 1,3-, 1,6- and 1,8-DNP, and 3,7- and 3,9-DNF . 3,7- and 3,9-DNF are new mutagens which were isolated in this study and they induced a frameshift type mutation in the Salmonella microsome test . Each derivative of DNP and DNF was detected at a concentration of 0.01 to 0.03 ppm in the particulates while the diesel engine was used under the condition of idling . 1,6- and 1,8-DNP were tumorigenic at the injection site in BALB/c male mice when a total of 2 and 1 mg, respectively, of the compounds was given subcutaneously . The incidences for tumors by 60 weeks were at a ratio of 50 and 30%, respectively, for 1,6- and 1,8-DNP-treated mice . 4-NQO and BaP, as positive control, induced tumors at the injection site in BALB/c mice when a total of 2 and 1 mg, respectively, of the compound was given . The incidences of tumors were observed at a high ratio of 90 and 93.4%, respectively, for 4-NQO- and BaP-treated mice . Histologically the tumors were diagnosed as malignant fibrous histiocytomas in all the tumors which developed . No tumors occurred at the injection site in mice given injections of 1,3-DNP . Tumorigenicity tests of 3,7- and 3,9-DNF are now being attempted using F344/DuCrj male rats . This animal experiment is now in progress . In the 3,9-DNF-treated rats (a total of 1 mg per rat), subcutaneous tumors developed in 8 of 11 rats up to 150 days after injection, and a part of a tumor resected from a rat showed the typical features of rhabdomyosarcoma. Microbiol Immunol, 1986, 30(8), 743 - 51 Staining of O-specific polysaccharide chains of lipopolysaccharides with ruthenium red; Kuno T et al.; S-form lipopolysaccharides (LPS) from Klebsiella strain LEN-1 (O3: K1-) and from Salmonella minnesota strain 1114 were positively stained with ruthenium red, whereas R-form LPS from Klebsiella strain LEN-111 (O3-: K1-) and Ra, Rb1, RcP+, Rd1P-, and Re LPS from the respective mutant strains of S . minnesota were not or only faintly stained by such treatment . From these results it was concluded that ruthenium red stains the O-specific polysaccharide chains of LPS . The appearance of stained preparations of S-form LPS suggested that the material responsible for this positive staining corresponded to the surface projections which were seen by the negative staining technique as attached to the ribbon-like structures and spherules of the LPS. Crit Rev Toxicol, 1986, 17(1), 23 - 60 Mutagenicity and carcinogenicity of nitroarenes and their sources in the environment; Tokiwa H et al.; Nitroarenes are postulated to play a principal part among mutagens/carcinogens which are induced in the combustion process and, in addition, are widely distributed in the environment . This review deals with the following points concerning nitroarene toxicity . Data on the mutagenicity of nitroarenes obtained by short-term bioassays are expected to provide us with sufficient information for us to determine their genotoxicity and carcinogenicity . Therefore, mutagenicity detected with Salmonella, Escherichia, and yeast test systems is discussed . Genotoxicity in mammalian cells is also important for determining the mutagenic properties of nitroarenes . In this article, mutagenicity in Chinese hamster ovary cells, sister chromatid exchanges, and cell transformation is summarized . The metabolism of nitroarenes in vivo and in vitro is of importance for determining their behavior and active forms . Therefore, current studies regarding metabolism of nitroarenes are described . Carcinogenicity of nitroarenes for animals has been reported by many workers . In this review, the incidence and histological features of tumors induced by nitroarenes are described . Furthermore, the possible association between human lung cancer and nitroarenes is discussed . Sources of nitroarenes in the environment are given . The results of various chemical tests for identifying nitroarenes are summarized, and speculation on the risk of nitroarenes for humans is presented. Zh Mikrobiol Epidemiol Immunobiol, 1986 Jan, (1), 24 - 9 {Comparison of the diagnostic value of methods for determining antibodies against the Salmonella group-B O-antigen}; Tregub AV et al.; The analysis of serum samples from 124 patients with the bacteriologically confirmed diagnosis of group B salmonellosis has revealed that the specific neutralization variant of the enzyme immunoassay (EIA) makes it possible to detect IgA, IgG and IgM more effectively than the indirect EIA variant and the passive hemagglutination test. Environ Mutagen, 1986, 8(1), 9 - 28 Classifying mutagens as to their specificity in causing the six possible transitions and transversions: a simple analysis using the Salmonella mutagenicity assay; Levin DE et al.; The standard Salmonella tester strains used to detect base substitution mutations carry the hisG428 ochre mutation (TA102 and TA104) and the hisG46 missense mutation (TA100) . These mutations can be reverted by base changes at their mutant his loci or at extragenic suppressor loci . The base changes resulting in each class of revertants of these mutations have been identified, and simple phenotypic screens have been developed to distinguish among them . Revertants at extragenic suppressor loci are distinguished from those at the his loci by their sensitivity to inhibitory histidine analogs . The four ochre suppressor loci of hisG428 are distinguished by their ability to support growth of nonsense mutants of phage P22 . These screens are the basis for a rapid and simple system for determining the base substitution specificity of mutagens using hisG428- and hisG46-containing tester strains . Diagnostic mutagens specific for each of the six possible base changes (transitions and transversions) have been identified . Using these diagnostic mutagens, two additional strains, each specifically reverted by a single base substitution mutation, have been developed to provide a minimum of two loci at which to detect each type of base change . The ability of this system to provide detailed information about mutational specificity in a variety of DNA repair backgrounds will allow further elucidation of the mechanisms of mutagenesis and DNA repair. J Immunol, 1986 Jan, 136(2), 710 - 5 C3 binds preferentially to long-chain lipopolysaccharide during alternative pathway activation by Salmonella montevideo; Joiner KA et al.; We studied the population of LPS molecules on Salmonella montevideo that bind C3 during alternative pathway activation in serum . LPS molecules of Salmonella are composed of lipid A:core oligosaccharide (one copy per molecule), substituted by an O-polysaccharide (O-PS) side chain, which is a linear polymer of 0 to greater than 60 O-antigen repeat units containing mannose . A mutant of S . montevideo called SL5222 that inserts galactose only into core oligosaccharide and mannose only into O-antigen subunits was grown with {3H}mannose and {14C}galactose, so that LPS molecules bearing large numbers of O-antigen subunits have high 3H to 14C ratios, whereas molecules with few O-antigen subunits have lower 3H to 14C ratios . Double-labeled SL5222 was incubated in C8-deficient (C8D) serum or C8D serum with 2 mM Mg++Cl2 and 10 mM ethylene glycoltetraacetic acid (MgEGTA C8D) . LPS molecules with covalently attached C3 were identified by binding to anti-C3 . LPS molecules that bound C3 under both incubation conditions had O chains seven to eight times longer than the average LPS molecule . SL5222 was then grown in suboptimal concentrations of mannose in order to decrease the number of LPS molecules with long O-PS side chains . C3 attached to progressively shorter chain molecules of LPS as the mannose input was lowered, but still chose the longest available molecules . This finding and recently published observations indicate that C3 can bind to LPS molecules with short O-PS side chains . We postulate that preferential attachment of C3 to long-chain LPS in SL5222 results because long-chain LPS molecules sterically hinder shorter chain LPS molecules from macromolecules . This study provides direct proof that the O-PS of LPS sterically hinders access of large molecules to the outer membrane and indicates that the LPS coat of these bacteria functions as a barrier against large protein molecules. J Mol Biol, 1985 Dec 20, 186(4), 791 - 803 Covalent structure of three phase-1 flagellar filament proteins of Salmonella; Wei LN et al.; Using recombinant DNA techniques, the covalent structure was determined for three flagellar filament proteins produced by Salmonella serotypes with phase-1 antigens a, c and d . Comparison of the results obtained, together with previous results for antigen i, indicated an overall structure in which conservation of amino acid sequence was absolute at both ends of the molecule and proceeded inwards with progressively greater variation . Very few differences in nucleotide sequence were detected in regions of amino acid conservation, which suggested that these areas of the gene may be involved in regulatory functions. Fundam Appl Toxicol, 1985 Dec, 5(6 Pt 1), 1065 - 74 Evaluation of mutagenic and carcinogenic properties of brominated and chlorinated acetonitriles: by-products of chlorination; Bull RJ et al.; The present study was undertaken to determine if chlorinated and brominated acetonitriles formed during the chlorination of drinking water possess mutagenic and/or carcinogenic properties . Chloroacetonitrile (CAN), dichloroacetonitrile (DCAN), trichloroacetonitrile (TCAN), bromochloroacetonitrile (BCAN), and dibromoacetonitrile (DBAN) were tested for their ability (1) to produce point mutations in the Salmonella/microsome assay, (2) to induce sister chromatid exchanges (SCE) in Chinese hamster ovary (CHO) cells in vitro, (3) to produce micronuclei in polychromatic erythrocytes in CD-1 mice, and (4) to act as tumor initiators in the skin of Sencar mice . DCAN and BCAN were found to be direct-acting mutagens in Salmonella . All five haloacetonitriles induced SCE in CHO cells in vitro . This activity paralleled the extent of chlorine substitution and was further enhanced in the dihaloacetonitrile series when bromine was substituted for chlorine . None of the haloacetonitriles showed evidence of activity in the mouse micronucleus assay . DBAN, BCAN, and CAN initiated tumors in the mouse skin with topical applications followed by a 20-week promotion schedule of 12-O tetradecanoylphorbol-13-acetate applications (p less than 0.02) . These data indicate that the haloacetonitriles do display mutagenic and carcinogenic properties in some test systems and the hazard associated with their occurrence in drinking water and production within the gastrointestinal tract require further evaluation. Sci Total Environ, 1985 Dec, 47, 361 - 70 Progress in the isolation and characterization of non-volatile mutagens in a drinking-water; van Rossum PG; Using the Ames Salmonella mutagenicity test (TA98, without S9), non-volatile mutagenic fractions were obtained by applying a separation scheme on XAD extracts of Pretoria drinking-water . The fractionations obtained were based on solubility, volatility, permeation and adsorption and the mutagenicity yield of each step was estimated . One mutagenic fraction consisted of humic like material, possibly together with polar polynuclear aromatic hydrocarbons. J Am Vet Med Assoc, 1985 Dec 1, 187(11), 1154 - 61 Clinical evaluation and prerelease management of American river otters in the second year of a reintroduction study; Hoover JP et al.; In the first year (1984) of a reintroduction study, 10 American river otters (Lutra canadensis) from Louisiana were transported to Oklahoma, held for 5 days for clinical evaluation, surgical implantation with intra-abdominal radiotelemetry devices, and then released in Oklahoma . Four of 10 otters released died within 32 days . Clinical evaluation indicated that respiratory tract disease, bacterial and parasitic infections, and inanition may have contributed to the death of these otters . In the second year (1985) of the study, an exotic feline diet was fed, and the holding period for 10 otters was increased to provide time for evaluation and treatment before surgery, postsurgical acclimation to Oklahoma, and reevaluation before release . Although the initial clinical findings on otters in the second year were similar to those found in the first year, otter body weights increased, and the prevalence and severity of clinical abnormalities decreased with treatment during the second-year holding period . Three of 10 second-year otters died during the holding period, and contributing causes of death were determined to be: trauma (hepatic hematoma), inanition, renal disease, pneumonia, salmonellosis (Salmonella anatum), and a retropharyngeal abscess (Klebsiella pneumoniae) . Seven healthy otters were reintroduced into Oklahoma in 1985, and postrelease deaths were not experienced. Food Chem Toxicol, 1985 Dec, 23(12), 1077 - 80 Absence of overt toxicity from feeding the flavonol, quercetin, to rainbow trout (Salmo gairdneri); Plakas SM et al.; The toxicity of the plant flavonol, quercetin, to rainbow trout (Salmo gairdneri) was investigated . Quercetin, which had been confirmed to be mutagenic in the Ames Salmonella/mammalian microsome test, was fed to trout at levels of 1 or 5% in the diet for 8 months . Survival, growth and feed conversion efficiency, selected haematological parameters and the relative weights of heart, liver and spleen were unaffected by the ingestion of quercetin, and there were no histopathological changes in any of the tissues examined. J Clin Microbiol, 1985 Dec, 22(6), 897 - 902 Quantitation of HeLa cell monolayer invasion by Shigella and Salmonella species; Niesel DW et al.; A major determinant in the virulence of Salmonella and Shigella spp . is the ability of these organisms to invade epithelial cells of the gastrointestinal mucosa and multiply intracellularly . The invasion of cell culture monolayers is a convenient experimental system to evaluate eucaryotic cell penetration and is correlated with the potential of a strain to cause human disease . We have developed an agarose-L agar overlay technique which allows for the convenient quantitation of the number of infected tissue culture cells in a monolayer . Bacterial strains were introduced onto antibiotic-free HeLa cell monolayers . Infected monolayers were washed, and noninternalized bacteria were counterselected with kanamycin (50 micrograms/ml) . The number of infected HeLa cells present was determined by overlaying the monolayer with distilled water-agarose (0.5 to 1.5%) followed by an equal volume of 2X L agar . Bacterial colonies formed over infected cells in 24 h at 37 degrees C, and wells were counted with a dissecting microscope under X2 power . Bacterial colonies were not observed with noninvasive variants of Shigella spp . To obtain countable wells (20 to 200 CFU) the multiplicity of infection or invasion times were adjusted . With a 90-min invasion time, the invasive potential of a strain was reflected by the multiplicity of infection needed to produce countable wells . The quantitation of bacterium-invaded cells by using standard bacteriological methods is a convenient and rapid method to evaluate the invasive potential of bacterial strains . Additionally, parameters essential for the invasive process can easily be investigated. J Clin Microbiol, 1985 Dec, 22(6), 1040 - 4 Method for the isolation of highly purified Salmonella flagellins; Ibrahim GF et al.; Ten different Salmonella serotypes were grown in a chemically defined medium supplemented with 0.01% yeast extract . After sedimentation of the cells by centrifugation, flagella were detached by exposure to pH 2 for 30 min at room temperature . The flagellaless cells were removed by centrifugation, and the flagellin in the supernatant was further purified by high-speed centrifugation, ammonium sulfate precipitation, and dialysis in 50,000-molecular-weight-cutoff tubing . The 10 flagellin preparations were of a high degree of purity, as demonstrated by electron microscopy, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and measurement of salmonella H and O agglutination titers of antisera raised in rabbits with the flagellin preparations as immunogens. Infect Immun, 1985 Dec, 50(3), 807 - 12 Local transfer of delayed-type hypersensitivity after Salmonella infection in mice; Attridge SR et al.; An adoptive local transfer system has been used to study the mediators of delayed-type hypersensitivity induced in mice by infection with Salmonella enteritidis 11RX . The cells which transfer this state of hypersensitivity to untreated recipients are nonadherent T lymphocytes with the surface phenotype Lyt 1+2-, and successful transfer requires compatibility at the I-A subregion of the H-2 complex . In these and other respects these cells are indistinguishable from those previously found to be responsible for in vitro lymphokine release upon culture with 11RX antigens. J Immunol, 1985 Dec, 135(6), 4178 - 82 Natural anti-bacterial activity against Salmonella typhi by human T4+ lymphocytes armed with IgA antibodies; Tagliabue A et al.; Peripheral blood mononuclear cells from normal volunteers possess natural anti-bacterial (NA) activity against S . typhi that can be measured in a 2-hr in vitro assay . Employing fractionation on nylon wool columns, Percoll gradients, plastic adherence, and E rosetting, the effector cell of NA activity appeared to be a lymphocyte of the T lineage rather than a macrophage, a B lymphocyte, or a large granular cell . Moreover, complement-dependent killing with monoclonal antibodies such as OKM1, OKB7, OKT8, 5.9 and the anti-natural killer cells AB8.28 did not reduce NA activity . On the contrary, this was completely inhibited when OKT3, OKT11, or OKT4 antibodies and complement were used to pretreat the effector lymphocytes . Indeed, T4+ cells sorted with a FACS displayed an extremely high NA activity against S . typhi . By pretreatment of peripheral lymphocytes with F(ab')2 fragments against human IgA, the NA activity was blocked . It is therefore suggested that NA activity by human cells might be a mechanism of defense against infections, acting as antibody-dependent cellular cytotoxicity expressed by T4+ lymphocytes coated with preexisting anti-Salmonella IgA antibodies. J Immunol, 1985 Dec, 135(6), 3869 - 77 Bacterial lipopolysaccharide, phorbol myristate acetate, and muramyl dipeptide stimulate the expression of a human monocyte surface antigen, Mo3e; Todd RF 3rd et al.; Exposure of mononuclear phagocytes to bacterial lipopolysaccharide (LPS), phorbol myristate acetate (PMA), or muramyl dipeptide (MDP) is known to stimulate a variety of cellular activities that include increases in phagocytosis, oxidative metabolism, synthesis and secretion of monokines, and cytotoxicity of microbes and tumor cells . We now report that culture of human peripheral blood monocytes in medium containing LPS, phorbol compounds, or MDP also results in the acquired expression of a plasma membrane antigen . Mo3e, as identified by a murine monoclonal antibody . Mo3e is barely detectable (by immunofluorescence flow cytometry) on freshly isolated monocytes, but is expressed in high antigen density after exposure of cells to E . coli, Salmonella minnesota, or Serratia marcescens LPS (at concentrations exceeding 0.1 ng/ml), PMA (and other biologically active phorbol compounds) (0.5 to 1 X 10(-8) M), or MDP (0.01 to 1 X 10(-6) M) . Mo3e expression stimulated by LPS is prevented by pretreatment of LPS with polymyxin B, suggesting that the lipid A portion of LPS is responsible for Mo3e induction (polymyxin B has no effect on Mo3e expression stimulated by PMA or MDP) . Culture of monocytes in medium containing protein synthesis inhibitors (or at 4 degrees C) blocks the acquisition of Mo3e . Recombinant IFN-gamma, which is also known to "activate" mononuclear phagocytes, does not stimulate Mo3e expression, although both LPS and IFN induce enhanced expression of monocyte Ia antigen . Analogous to their stimulatory effect on monocytes, LPS and PMA induce Mo3e expression by the human monocytic cell line, U-937 . On the basis of these observations, Mo3e may represent an immunologic marker for monocyte activation stimulated in vitro by LPS, PMA (and related compounds), and MDP. Biochem J, 1985 Dec 1, 232(2), 379 - 83 Characteristics of lipopolysaccharide interaction with human peripheral-blood monocytes; Warner SJ et al.; The interaction between radioiodinated lipopolysaccharide from Escherichia coli 0111:B4 (125I-LPS) and human peripheral-blood monocytes was studied . The association of 125I-LPS with monocytes at 37 degrees C appeared to depend on binding to the cell membrane with subsequent internalization of the molecule, and was not saturable with time (up to 2 h) or 125I-LPS concentration (up to 10 micrograms/ml) . There was no apparent difference in the behaviour of unlabelled LPS and 125I-LPS with respect to monocyte association . 125I-LPS association with monocytes was inhibited by LPS and O-polysaccharide from E . coli 0111:B4 and Salmonella typhi 0901, but not by lipid A or polymyxin B . We propose that the mechanism of human monocyte stimulation by LPS involves polysaccharide-dependent binding to the cell membrane followed by internalization of the LPS molecule . We were unable to demonstrate a specific LPS receptor such as that found on murine B-lymphocytes. Zh Mikrobiol Epidemiol Immunobiol, 1985 Dec, (12), 67 - 9 {Role of peritoneal macrophages in the development of an experimental Salmonella infection}; Boichenko MN et al.; The effect produced on the course of Salmonella infection in mice by the removal of peritoneal macrophages with agarose has been studied . Peritoneal macrophages have been shown to control the multiplication of faintly virulent and virulent S . typhimurium strains in the spleen of mice . In immune mice the elimination of the virulent strain of the causative agent of superinfection may occur without the control of peritoneal macrophages. Am Ind Hyg Assoc J, 1985 Dec, 46(12), 741 - 6 Method for detecting the 3-hydroxymyristic acid component of the endotoxins of gram-negative bacteria in compost samples; Kirschner D et al.; An analytical chemical method for the 3- or beta-hydroxymyristic (BHM) acid component of endotoxins has been developed for the lipopolysaccharide (LPS) of E . coli, intact E . coli, and sewage sludge compost . Endotoxins are the pyrogens associated with the outer membranes of many gram-negative bacteria, for example, E . coli and Salmonella . The BHM acid content was used as a chemical marker for endotoxin presence, since BHM acid is present in the molecular subunit (Lipid-A) responsible for the toxicity and is the most abundant saturated fatty acid in that subunit . BHM acid quantification thus complements the Limulus bioassay to detect gram-negative bacteria presence in such samples as cotton and other dusts, blood, water, compost and air samples . BHM acid was isolated after digestion, ether extraction, alkaline hydrolysis, and ether extraction . The free acid was quantitated as the methyl ester using two GC columns as a screening method or by GC/MS for confirmatory purposes . Recoveries were unreliable below 15 ng of BHM acid . By the use of the 2-column screening technique, the amounts of BHM equivalent in E . coli LPS, intact E . coli and compost in micrograms BHM acid/g substrate were (arithmetic mean +/- standard deviation), respectively: 56 120 +/- 2200; 2650 +/- 339; and 14.7 +/- 5.7. Mutat Res, 1985 Dec, 158(3), 125 - 7 Evaluation of the mutagenic activity of some aza-aromatic hydrocarbons; Tanga MJ et al.; The mutagenic activity of 7 aza-aromatic hydrocarbons, which are suspected of being environmental pollutants, was assessed using the Salmonella assay . The compounds tested were: 1-azachrysene, 2-azachrysene, 4-azachrysene, 1-azabenz{a}anthracene, 2-azabenz{a}anthracene, 9-azabenz{a}anthracene, and 12-benzo{a}pyrene . None of the compounds was mutagenic in the absence of S9, but all were mutagenic in the presence of S9. Mutat Res, 1985 Dec, 158(3), 111 - 7 Effect of induction by DDT on metabolism and mutagenicity of benzo{a}pyrene; Bonin AM et al.; Liver microsomal enzymes are essential for the detection of benzo{a}pyrene (B{a}P)-mediated mutagenesis in the Salmonella/mammalian microsome mutagenicity test and, furthermore, this mutagenicity is considerably enhanced by induction of hepatic enzymes involved with drug metabolism . Although Aroclor 1254 is most commonly used for induction of S9 enzymes, DDT is also capable of this induction . This paper reports a comparison of liver S9 fraction induced by the two agents: there is a marked difference in their concentration optima for metabolism of B{a}P; greater numbers of revertant colonies are seen with Aroclor-induced S9, which is optimal at a concentration of 10% (v/v), whereas DDT-induced S9 is optimal at 2.5% (v/v); Aroclor induces aryl hydrocarbon hydroxylase (AHH), cytochrome P-450 and epoxide hydrase while DDT induces only AHH, to about half the level detected in the Aroclor-induced S9 fraction . A comparison of metabolite distribution for Aroclor- and DDT-induced hepatic microsomes reveals quantitative differences only . DDT-induced microsomes yield a greater proportion of B{a}P-4,5-oxide and its metabolic product B{a}P-4,5-dihydrodiol than do Aroclor-induced microsomes . Time course studies on the mutagen half-life measured on the agar plate provides good evidence that metabolites responsible for mutagenicity were different for each inducer. Mutat Res, 1985 Dec, 158(3), 105 - 10 Formation of bacterial mutagens from the reaction of chewing tobacco with nitrite; Whong WZ et al.; Using the Salmonella/microsome assay system, the mutagenicity of chewing tobacco extracts (CTE) treated with and without sodium nitrite under acidic conditions was examined . Mutagenic activity was found only for nitrite-treated CTE in both tester strains, TA98 and TA100, and was independent of metabolic activation . Formation of mutagenic substances from CTE by nitrite was dependent on acidic pHs (the highest at pH 2) and could be inhibited by ascorbate . The mutagenic potency of CTE plus nitrite was proportional to the content of nitroso compounds generated in the reaction mixture, indicating that the nitrosation process was involved . The possible in vivo nitrosation and the potential health effect are discussed. Infect Immun, 1985 Dec, 50(3), 925 - 8 Enteroadhesion fimbriae and enterotoxin of Escherichia coli: genetic transfer to a streptomycin-resistant mutant of the galE oral-route live-vaccine Salmonella typhi Ty21a; Yamamoto T et al.; An enterotoxigenic Escherichia coli plasmid encoding colonization factor antigen (CFA) I fimbriae and heat-stable toxin was transferred into a streptomycin-resistant mutant of the Salmonella typhi galE strain Ty21a (a live attenuated oral typhoid vaccine) . The virulence plasmid-carrying transconjugants produced CFA I fimbriae and heat-stable toxin . The marked production of CFA I fimbriae was observed even in a vaccine medium for Ty21a . The data lead to a new type of potential live oral vaccine, S . typhi Ty21a producing enteroadhesion fimbriae. J Trop Med Hyg, 1985 Dec, 88(6), 377 - 81 Current clinical patterns of typhoid fever: a prospective study; Gupta SP et al.; This paper reports on a prospective study comprising 125 consecutive adult cases of typhoid fever diagnosed on the basis of positive cultures for typhoid organisms . Salmonella typhi infection was found to be more frequent (89.6%) than S . paratyphi A & B (10.4%) . Onset of the disease was usually insidious and the classical step-ladder pattern of fever was uncommon (12%) . Rose spots were observed in 9.6% cases . Gut perforation was more common, while typhoid toxaemia and peripheral circulatory failure were less frequent than in most of the series reported from India . Both these variations are ascribed to the widespread use of corticosteroids in our patients . Gut perforation alone accounted for three-quarters of the deaths. J Virol, 1985 Dec, 56(3), 1030 - 3 Genetic and DNA mapping of the late regulation and lysis genes of Salmonella bacteriophage P22 and coliphage lambda; Wiggins BA et al.; Genetic and DNA heteroduplex analyses of lambda imm22 hybrid phages were used to compare the Salmonella bacteriophage P22 and coliphage lambda genes which control late gene regulation and lysis . Homologous DNA sequences were correlated with P22 gene 23 and lambda gene Q (late gene regulation) and with P22 gene 13 and lambda gene S (lysis control) . Nonhomologous DNA sequences were correlated with P22 gene 19 and lambda gene R (lysozyme and endolysin) and with the region encoding the P22 alpha and lambda 6S transcripts. Cell Biophys, 1985 Dec, 7(4), 283 - 91 Chemiluminescence response of the human polymorphonuclear neutrophil to lipopolysaccharides; Nicotra J et al.; Polymorphonuclear neutrophils (PMN) respond to a variety of stimuli with a sequence of reactions that lead to the production of "active oxygen" species, including H2O2, free radicals, such as superoxide (O2-.) and hydroxyl (HO.), and singlet molecular oxygen (1O2) . Some of these can oxidize (5-amino-2,3-dihydrophthalazine 1,4-dione) (luminol) to the ground state aminophthalate ion; this reaction sequence is accompanied by the generation of a photon and forms the basis for the chemiluminescence (CL) response . In this work we used a dedicated photon counting instrument to record CL from PMN incubated with bacterial lipopolysaccharide (LPS) . We have studied the CL response to the LPS from Escherichia coli strains 026:B6 and 055:B5, as well as Salmonella minnesota RE 595 and have determined that CL requires heat-labile serum factors, these most likely being intact components of the complement system. Poult Sci, 1985 Dec, 64(12), 2394 - 6 Dendritic cells of the chicken spleen are capable in vivo of giant cell formation; Olah I et al.; In this report, we offer evidence that carrageenan, a polyclonal B-cell mitogen, and Salmonella O antigen, when administered together, can induce in vivo multinucleated giant cells from dendritic cells in the chicken spleen. Presse Med, 1985 Nov 16, 14(39), 2005 - 7 {Treatment of acute colectasia not due to cryptogenic colitis . 4 cases}; Maroy B et al.; Four patients with acute colonic pseudo-obstruction were treated by colonoscopic aspiration . This treatment proved sufficient in 1 case due to Salmonella colitis and 1 case of parkinsonian dysautonomia . It has made it possible to diagnose a pyocholecyst masked by the colonic dilatation it had provoked, and facilitated its surgical treatment . A transient result was obtained in a case of otherwise asymptomatic choleperitoneum . Colonoscopy was relatively easy, perfectly well tolerated and always useful . It is therefore recommended for the treatment of acute colonic pseudo-obstruction except in cryptogenic colitis where its effectiveness and safety have not been demonstrated. Zh Mikrobiol Epidemiol Immunobiol, 1985 Nov, (11), 60 - 4 {Etiological structure of salmonellosis and the serotype passage of salmonellae isolated in separate regions of the USSR in 1980-1982}; Rozhnova SSh et al.; At the period of 1980-1982 the isolation of salmonellae belonging to 394 serovars was registered in the USSR . Of these, 116 Salmonella serovars were registered in the USSR for the first time . 12 dominating serovars constituted 83.1% of salmonellae isolated from humans, 99% of salmonellae isolated from animals and 70% of all salmonellae isolated from different environmental objects . S . typhimurium was the predominant serovar, found to determine 50% of cases of Salmonella infection . The isolation rate of S . infantis and S . virchow was shown to increase . The existence of definite ecological relationships between infective agents isolated from different sources was established. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1985 Nov, 260(3), 339 - 41 {Salmonella eschberg--report on the isolation of a new serovar}; Rohr HP; The serological and biochemical characteristics of a so far unknown serovar of Salmonella subspecies I with the serological formula 9,12:d:1,7 is described . It has been named after a borough of Saarbrucken: Salmonella eschberg. Mol Immunol, 1985 Nov, 22(11), 1265 - 71 Murine antibody response to the glycolipid asialo GM1 adsorbed to Salmonella; Higgins TJ; The murine antibody response to the asialo GM1 adsorbed to stripped Salmonella was studied . IgM and IgG responses were obtained which did not fall to baseline within 200 days after the initial immunization . The antisera from the experimental group showed strong reactivity to asialo GM1 and measureable amounts of activity to asialo GM2 . Sera from control animals receiving Salmonella alone also reacted to asialo GM2 . Additional experiments showed that the anti-asialo GM1 and the anti-asialo GM2 activities were the result of separate antibody populations . Antisera from an early bleed of the experimental group showed specific lysis of asialo GM1 bearing macrophages; however, later bleeds from both experimental and control groups lysed asialo GM1 expressing and normal macrophages equally . These results suggest an autoimmunity had been generated . The suitability of this protocol for generating specific antiserum and immunizing in preparation for generating monoclonal antibodies is discussed. Environ Health Perspect, 1985 Nov, 63, 187 - 94 Statistical studies in genetic toxicology: a perspective from the U.S . National Toxicology Program; Margolin BH; This paper surveys recent, as yet unpublished, statistical studies arising from research in genetic toxicology within the U.S . National Toxicology Program (NTP) . These studies all involve analyses of data from Ames Salmonella/microsome mutagenicity tests, but the statistical methodologies are broadly applicable . Three issues are addressed: First, what is a tenable sampling model for Ames test data, and how does one best test the adequacy of the Poisson sampling assumption? Second, given that nonmonotone dose-response curves are fairly common in the Salmonella assay, what new statistical techniques or modifications of existing ones seem appropriate to accommodate to this reality? Finally, an intriguing question: How can the extensive NTP Ames test data base be used to assess the characteristics of any mutagen-nonmutagen decision rule? The last issue is illustrated with the commonly used "two-times background" rule. Am J Vet Res, 1985 Nov, 46(11), 2300 - 10 Studies on the pathogenesis of Salmonella heidelberg infection in weanling pigs; Reed WM et al.; Experiments were conducted to define the pathogenic potential of Salmonella heidelberg in weanling pigs . Oral inoculation with S heidelberg resulted in severe catarrhal enterocolitis with accumulation of large amounts of fluid in the small intestine and colon . Salmonella heidelberg was demonstrated, with fluorescence microscopy and bacteriologic cultural techniques, to colonize the ileum, to invade ileal mucosal enterocytes, and to reach mesenteric lymph nodes and extraintestinal tissues by 8 hours . In 5 pigs, intestinal loops were surgically prepared and inoculated with S heidelberg (to determine its invasiveness) . Microscopically, there were atrophy of villi, erosion of enterocytes, and neutrophilic infiltration in the lamina propria . Ultrastructurally, intracellular bacteria were demonstrated in villous and cryptal enterocytes, as well as in macrophages of the lamina propria . Bacteria were morphologically intact, occurred free and membrane-bound and caused no detectable cytotoxic effect to the cell. Am J Hosp Pharm, 1985 Nov, 42(11), 2449 - 54 Permeability of four disposable protective-clothing materials to seven antineoplastic drugs; Laidlaw JL et al.; The permeability of four types of protective-clothing material to seven injectable antineoplastic drugs was studied . The protective materials tested were Saranex-laminated Tyvek, polyethylene-coated Tyvek, nonporous Tyvek, and Kaycel . Circles 6 cm in diameter were cut from a single garment of each material and exposed to each drug . Permeation of cisplatin, etoposide, mitomycin, cyclophosphamide, carmustine, and thiotepa was assessed by the Salmonella mutagenicity test after four hours of exposure . Doxorubicin permeation was assessed qualitatively over an eight-hour exposure period using a coloration assay . Saranex-laminated Tyvek was not permeable under the test conditions . Polyethylene-coated Tyvek was slightly permeable to thiotepa and carmustine . Nonporous Tyvek was permeable to all seven drugs, and the Kaycel garment was permeable to all of the drugs except etoposide . In no instance did permeation exceed 3.3% of the applied drug dose . Saranex-laminated Tyvek was the most protective of the barrier garments, followed closely in effectiveness by the polyethylene-coated Tyvek . Clothing made from these two Tyvek composites would allow less air flow and, therefore, would be less comfortable to wear for extended periods . Garments made of nonporous Tyvek or Kaycel would be more comfortable, but their use should be accompanied by an awareness of their potential permeability to certain antineoplastic drugs. Mutat Res, 1985 Nov, 144(3), 197 - 202 Genotoxicity of carcinogenic N-nitrosopropylamine derivatives in the hepatocyte primary culture/DNA-repair test; Yamazaki H et al.; The genotoxicity of N-nitrosodipropylamine, 8 of its oxidized derivatives and N-nitroso-2,6-dimethylmorpholine was examined in the hepatocyte primary culture (HPC)/DNA repair test . Nine N-nitrosamines which are known to be carcinogenic and mutagenic were clearly positive in the HPC/DNA-repair test . N-Nitroso(2,3-dihydroxypropyl) (2-hydroxypropyl)amine did not elicit DNA repair, but showed a borderline mutagenic response in the Salmonella/microsome test . Thus, the HPC/DNA-repair test displays a comparable capacity to the bacterial mutagenesis test for detecting the genotoxic effects of this class of carcinogens. Cancer Res, 1985 Nov, 45(11 Pt 2), 5859 - 66 Deacetylation to 2-aminofluorene as a major initial reaction in the microsomal metabolism of 2-acetylaminofluorene to mutagenic products in preparations from rabbit lung and liver; Aune T et al.; The rabbit pulmonary and hepatic microsomal pathways for the metabolism of 2-acetylaminofluorene (AAF) and 2-aminofluorene (AF) to mutagenic products were investigated by means of high performance liquid chromatography and the Salmonella mutagenicity assay . Mutagenic activity approached a maximum with increasing concentrations of AAF incubated with hepatic microsomal preparations and Salmonella; with pulmonary microsomal preparations, mutagenic activity was proportional to the concentration of AAF over the range examined . The mutagenic activities of AF exhibited typical saturation kinetics with both hepatic and pulmonary microsomal preparations . Approximately 7 times more AF than N-hydroxy-2-acetylaminofluorene (N-hydroxy-AAF) was formed in incubations of AAF (0.5 mM) with hepatic microsomal preparations . When AAF was incubated with pulmonary microsomal preparations, formation of AF, but not N-hydroxy-AAF, was detected . The inclusion of paraoxon in the pulmonary incubations blocked the formation of AF but did not lead to the recovery of any N-hydroxy-AAF . We conclude that the metabolism of AAF to mutagenic products in pulmonary microsomal preparations from rabbits is initiated primarily, if not entirely, by deacetylation of AAF to AF . The mutagenic activity of AAF with the pulmonary microsomal preparations is limited by the deacetylase activity which, like mutagenic activity, exhibits a linear relationship with the concentration of AAF . On the basis of the rates of formation of AF and N-hydroxy-AAF and their mutagenic activities, we estimate that about 60% of the hepatic metabolism of AAF to mutagenic products is dependent upon deacetylation of AAF and subsequent oxidation of the AF formed. Mutat Res, 1985 Nov, 144(3), 213 - 9 Metabolic activation of hepatocarcinogens in chronic hepatitis B; De Flora S et al.; S9 fraction pools of liver biopsy samples, collected from 129 patients in two consecutive studies, were comparatively assayed for their ability to activate aflatoxin B1 (AFB1) and a tryptophan pyrolysate product (Trp-P-2) in a miniaturized Salmonella mutagenicity test system . Metabolic activation was not affected to a significant extent by most of the monitored variability factors, such as sex, alcohol, cigarette smoking and liver histology (minimal changes, chronic persistent (CPH) or active (CAH) hepatitis, CAH steatosis, or cirrhosis) . Conversely, a significant enhancement of activation was observed for AFB1 in cases of mild CAH and especially for Trp-P-2 in hepatitis B virus carriers, irrespective of their histologic diagnosis. J Clin Invest, 1985 Nov, 76(5), 1755 - 64 Therapeutic concentrations of glucocorticoids suppress the antimicrobial activity of human macrophages without impairing their responsiveness to gamma interferon; Schaffner A; By exposing human blood-derived macrophages and alveolar macrophages in vitro to dexamethasone, we showed in these studies that glucocorticoids markedly suppress the antimicrobial activity of macrophages but not macrophage activation by lymphokines . As little as 2.5 X 10(-8) mol/liter of dexamethasone prevented macrophages from inhibiting germination of Aspergillus spores or from eliminating ingested bacteria such as Listeria, Nocardia, or Salmonella . Damage to macrophage function was inhibited by progesterone and appeared to be receptor-mediated . In accordance with in vivo observations, dexamethasone required 24-36 h to suppress antimicrobial activity . While glucocorticoids interfered with base-line activity of macrophages, dexamethasone concentrations comparable to drug levels in patients had no effect on macrophage activation . Proliferating lymphocytes and gamma-interferon thus increased the antimicrobial activity of phagocytes exposed to glucocorticoids over that of control cells . Macrophage activation and correction of the dexamethasone effect by gamma-interferon, however, was dependent on the pathogen . The lymphokine enhanced the antimicrobial activity of dexamethasone-treated macrophages against Listeria and Salmonella but not against Aspergillus or Nocardia . Dexamethasone-induced damage to the antimicrobial activity of human macrophages in vitro parallels observations that glucocorticoids render laboratory animals susceptible to listeriosis and aspergillosis by damaging resident macrophages . Suppression of macrophage antimicrobial activity should thus be considered when treating patients with glucocorticoids; its prevention by gamma-interferon might be beneficial for some but not all pathogens. Jpn J Antibiot, 1985 Nov, 38(11), 3195 - 216 {Bacteriological, pharmacokinetic and clinical studies on aztreonam in the pediatric field . Pediatric Study Group of Aztreonam}; Fuyii R et al.; This report summarizes the results of joint studies in pediatrics on aztreonam, the first monobactam antibiotic for practical use . Pharmacokinetics was studied in 53 cases administered with 10, 20, 40 and 50 mg/kg of aztreonam (AZT) by intravenous injection and 20 cases with 10, 20, 30, and 40 mg/kg by drip infusion . All the cases had normal hepatic and renal functions at the administration . T1/2 was in a relatively fixed range of 1.35-1.56 hours in intravenous injection cases and 1.30-1.55 hours in drip infusion . One hour after commencing administration of standard 20 mg/kg, the serum concentrations were 50.18 +/- 4.24 micrograms/ml in intravenous injection and 116.33 +/- 10.18 micrograms/ml in drip infusion and even 6 hours after the end of the administration, they were 5.80 +/- 1.16 micrograms/ml and 3.38 +/- 0.58 micrograms/ml, respectively . The cerebrospinal fluid penetration was studied on suppurative meningitis (5 cases) and nonbacterial meningitis (3 cases) . The penetration was generally good with sufficient concentration for meningitis caused by E . coli and H . influenzae . Amount of the penetration decreased as the cases were improved . Twenty-nine (29) cases were excluded and 262 cases of total 291 were clinically assessed, and the pathogen-isolated 167 cases of 262 were principally analyzed . Efficacy of AZT was "excellent" for all 3 cases of E . coli sepsis and 1 case of N . meningitidis meningitis and "good" for 1 case of H . influenzae meningitis . The effective rate was 94.6% for 37 pneumonia cases, 94.7% for 76 UTI cases and 88.5% on the whole including as many as 98 "excellent" cases . However, the effective rate for 21 enteritis cases was only 52.4% . Similar trend was observed in the pathogen-unknown group and overall effective rate of total 267 cases was 86.8% . The clinical effect by pathogen was 97.7% for 44 E . coli cases and 97.1% for 34 H . influenzae cases, showing excellent results for the GNB group . AZT was also effective for 8 out of 11 P . aeruginosa cases . With regard to microbiological effect by pathogen, AZT showed a high rate of bacterial elimination for GNB, primarily 98.1% for E . coli and 100% for H . influenzae followed by 76.9% for P . aeruginosa . However, it was only 30.0% for Salmonella . Excluding the Salmonella cases, GNB elimination rate was 93.5% . Clinical and microbiological dose response was not clear partly because, same as the previous studies, the effective rate of AZT was high . It was considered, however, standard dose of 20 mg/kg X 3 approximately 4 times a day was recommendable.(ABSTRACT TRUNCATED AT 400 WORDS) Vet Clin North Am Food Anim Pract, 1985 Nov, 1(3), 529 - 39 Salmonellosis in calves; Rings DM; Despite the efforts of both physicians and veterinarians, the number of cases of salmonellosis per year has held steady or risen . The ability of the organism to live in many different animal species and under inhospitable environmental conditions is likely responsible for Salmonella's prevalence today . Diverse clinical signs occur in salmonellosis; they range from unthriftiness to explosive, necrotizing diarrheas with high mortality . Secondary complications of pneumonia, bone and joint infections, and meningoencephalitis can result from calfhood infections . Treatment of enteric salmonellosis is chiefly aimed at maintaining fluid, acid-base, and electrolyte balance . Bacteremic or septicemic calves also require systemic antibiotics . The control measures for salmonellosis are based on sanitation and management . Individual calf hutches or pens provide adequate isolation if sufficient spacing and good sanitation are maintained . The Salmonella vaccines presently available provide limited protection; however, live vaccines made from auxotrophic strains of Salmonella appear to be more efficacious. Br J Cancer, 1985 Nov, 52(5), 725 - 31 The mutagenic activity of razoxane (ICRF 159): an anticancer agent; Albanese R et al.; The mutagenic activity of razoxane (ICRF 159) was studied using the Salmonella/microsome assay and rodent bone-marrow micronucleus and metaphase assays . Razoxane (up to 5000 micrograms/plate) did not cause an increase in the mutation frequency in the Salmonella/microsome assay . In the mouse micronucleus assay razoxane (200 and 400 mg kg-1 i.p.) was cytotoxic to the bone marrow cells (which limited the analysis) but an increase in micronucleated polychromatic erythrocytes was observed in razoxane dosed animals (5-fold compared to control value) . In the Chinese hamster metaphase assay razoxane (up to 500 mg kg-1 orally) induced abnormal chromosome condensation and an increase in structural chromosome aberrations (7 fold compared to control value) as well as an increase in the number of polypoid cells (8-fold compared to control value) . The mutagenic effect of razoxane was restricted to eukaryotic organisms and was associated with specific chromosomal changes. Arch Intern Med, 1985 Nov, 145(11), 1968 - 71 Salmonella bacteremia associated with the acquired immunodeficiency syndrome (AIDS); Nadelman RB et al.; Six cases of bacteremia due to serotypes of Salmonella enteritidis are described in patients with the acquired immunodeficiency syndrome (AIDS) . In four instances the bacteremia was recurrent despite appropriate antimicrobial treatment . Neither a gastrointestinal tract source nor any other focus of infection could be identified in four of the six patients . In one patient an unusual Salmonella infection, ie, pyelonephritis, was noted . The discovery of Salmonella sepsis led in four cases to the initial diagnostic consideration of AIDS, which was ultimately confirmed . When unexplained Salmonella bacteremia occurs in populations known to be at high risk for the development of AIDS, a thorough evaluation for this disorder should be undertaken. Mutat Res, 1985 Nov, 144(3), 137 - 40 Automated modification of the Ames test with COBAS Bact; Arni P et al.; The automatic analyser for microbiology "COBAS Bact" from Roche, supplemented by a Hewlett-Packard 9816S is used to automate the Salmonella mutagenicity test, developed by Ames . More than 30 compounds were tested in this system and the results were shown to be in good agreement with those obtained with the standard Ames test. Infect Immun, 1985 Nov, 50(2), 586 - 7 Plasmid-cured Salmonella enteritidis AL1192 as a candidate for a live vaccine; Nakamura M et al.; We report the immunizing capacity of Salmonella enteritidis AL1192, a strain that has been cured of a 36-megadalton plasmid, to protect ddY mice against subsequent challenge with virulent salmonellas . This strain, which was given subcutaneously at a dose of 10(6) organisms, provided significant protection against oral, subcutaneous, or intraperitoneal challenge by virulent wild-type strains of not only S . enteritidis, but also S . dublin, S . naestved, and S . typhimurium. Clin Exp Immunol, 1985 Nov, 62(2), 242 - 7 Cellular immunity against Salmonella typhi after live oral vaccine; Tagliabue A et al.; Seventeen adult volunteers were vaccinated orally with the live attenuated Salmonella typhi mutant strain Ty21a . Their peripheral blood mononuclear cells were tested at different times after vaccination for direct cell-mediated activity against bacteria, employing a simple short-term in vitro assay . It was observed that 16/17 of the vaccinated subjects acquired the capacity to express specific cellular immunity against S . typhi which lasted from 15 days to at least 3 years . The effector cell of the in vitro antibacterial activity was preliminarily characterized as a non-adherent T3+, T8-, T4+ lymphocyte . In parallel, mice immunized orally with S . typhimurium and proving resistant to reinfection were tested employing the same in vitro assay . Also in this case peripheral and, most important, intestinal lymphocytes were able to express cellular immunity against the agent of murine typhoid . It is concluded that administration of live oral vaccine against S . typhi results in the induction of specific cellular immunity which is expressed at the peripheral and, probably, also at the intestinal level. J Pharmacol Exp Ther, 1985 Nov, 235(2), 470 - 4 Protective effect of a selective leukotriene antagonist in endotoxemia in the rat; Cook JA et al.; The role of lipoxygenase metabolites as inflammatory mediators in endotoxic shock remains uncertain . In the present study, the effects of a selective leukotriene (LT) D4/LTE4 antagonist, LY171883, 1-{2-hydroxy-3-propyl-4-{4-(1H-tetrazol-5-YL)-butoxy}-phenyl ethanone}, on endotoxin-induced sequelae in the rat were assessed . LY171883 was given as a bolus (30 mg/kg i.v.) 10 min before Salmonella enteritidis endotoxin (40 mg/kg) in ketamine-anesthetized (200 mg/kg i.m.) rats, followed by an infusion (10 mg/kg/hr) starting at 30 min postendotoxin . Carotid artery blood pressures were determined at 10 min before and at intervals up to 240 minutes postendotoxin administration . Compared to shocked vehicle controls LY171883 attenuated (analysis of variance, P less than .02) the initial (0-30 min), but not the later, endotoxin-induced hypotension . LY171883 prevented completely (analysis of variance, P less than .001) the neutropenia (0-180 min), but not the thrombocytopenia induced by endotoxin . Hemoconcentration resulting from endotoxemia was reduced by LY171883 compared to the vehicle control group (P less than .02) . These data demonstrate that this LTD4/LTE4 antagonist has significant salutary actions in endotoxemia and suggest that LTs may contribute to some endotoxin-induced sequelae. Infect Immun, 1985 Nov, 50(2), 420 - 4 Plasmid-mediated virulence in Salmonella dublin demonstrated by use of a Tn5-oriT construct; Chikami GK et al.; Salmonella dublin, a serotype which causes invasive disease in cattle and humans, carries a characteristic 80-kilobase plasmid (pSDL2) . We were able to cure the plasmid from a strain of S . dublin . The cured strain was avirulent for mice by either the oral or intraperitoneal route of infection . A derivative of Tn5 which contains the transfer origin of the broad-host-range plasmid RK2 (Tn5-oriT) was transposed onto pSDL2, allowing mobilization of the plasmid by an RK2 helper plasmid . Reintroduction of the pSDL2 derivative plasmid into the cured strain restored virulence, demonstrating that the plasmid is necessary for virulence . These studies also demonstrate the usefulness of the Tn5-oriT construct for genetic manipulations. Clin Exp Immunol, 1985 Nov, 62(2), 248 - 55 Relationship between immune system and gram-negative bacteria . III . Functional analysis of human peripheral blood lymphocyte subpopulations separated by cytoadherence with Salmonella minnesota Rb; Antonaci S et al.; Spontaneous adherence of bacteria to human peripheral blood mononuclear cells (PBMC) represents a useful tool for analysis of lymphocyte subsets with different functions . We have recently shown that PBMC can be divided into 2 populations based on their ability to bind Salmonella minnesota R345 (Rb) bacteria . By using these procedures, here, we provide evidence that Rb-bound and Rb-unbound PBMC populations give similar proliferative responses to phytohemagglutinin (PHA) and concanavalin A (Con A), while the pokeweed mitogen (PWM)-induced proliferative and differentiative responses are higher in the Rb-unbound than in the Rb-bound PBMC fraction . Moreover, enhanced PWM-induced responses are obtained in Rb-unbound cell cultures enriched for T4+ cells . When B (non-E rosetting) cells are cultured with purified T lymphocytes from the Rb-bound (T-Rb+) and Rb-unbound (T-Rb-) fractions, comparable PWM-induced mitogenic responses are observed . The T-Rb- population contains a higher percentage of cells expressing T4+ phenotype, and when added to B cell cultures a more elevated PWM-induced IgA, IgG and IgM synthesis is observed than in B cell cultures containing T-Rb+ cells . These results suggest that the T-Rb- fraction is enriched for T cells which help IgA, IgG and IgM responses. Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi, 1985 Nov, 18(4), 256 - 63 Diagnostic value of a single Widal test; Pu SJ et al.; The Widal test was performed on 90 blood specimens from typhoid fever patients, on 21 blood specimens from nontyphoid salmonellosis patients and on 46 nontyphoid febrile patients . Of 90 typhoid fever patients, 58 (64.4%) had H agglutinin titer of 1:160 or more and 55 (61.1%) had O agglutinin titer of 1:160 or more . Salmonella typhi H and/or O titer of 1:160 or more occurred in 70 (77.8%) of 90 typhoid fever patients and in 5 (23.8%) of 21 nontyphoid salmonellosis . Only one of the 46 (2.2%) nontyphoid febrile patients showed O agglutinin titer of 1:160, a case which was proven subsequently to be a case of systemic lupus erythematosus . Either O or H can reach to diagnostic level during the first week of typhoid fever, and can be helpful in diagnosis of the illness . In view of the high specificity (91.0%), sensitivity (77.8%) and accuracy (83.4%), the Widal test still has value in the diagnosis of typhoid fever. J Infect Dis, 1985 Nov, 152(5), 954 - 64 Cross-reactivity of rabbit antibodies to lipopolysaccharides of Escherichia coli J5 and other gram-negative bacteria; Siber GR et al.; Antiserum to rough gram-negative mutants such as Escherichia coli J5 and Salmonella minnesota Re595 is thought to neutralize the toxic effects of lipopolysaccharides (LPSs) . To verify that such antisera are capable of binding heterologous endotoxins, we examined IgG and IgM class antibodies induced in rabbits to a variety of LPSs . Immunization with rough mutants or lipid A induced high IgG antibody responses to the homologous purified LPS and relatively low but significant responses to heterologous LPSs . Increases in IgM antibodies were also primarily to homologous LPS . Immunization with smooth organisms induced little or no antibody to heterologous LPSs . Soluble LPS, outer membrane vesicles, and whole bacteria produced strong homologous inhibition but little or no heterologous inhibition in enzyme-linked immunosorbent assays . Cross-adsorption of antisera to rough mutants suggested that the IgG and IgM antibodies induced to heterologous LPS were adsorbed by the heterologous LPS and not by the core LPS used to immunize the animals . Rabbit antibody directed to J5 or Re595 LPS fails to bind to any substantial degree to heterologous LPS . Immunization with whole bacterial vaccines, particularly the rough mutants and lipid A, does increase antibody to a wide variety of antigens . The possibilities that the protective effects of antisera to rough mutants are due to a polyclonal antibody response or to the induction of as yet unidentified factor(s) deserve further investigation. J Biol Chem, 1985 Oct 25, 260(24), 12974 - 7 Selective detection of 3-deoxymannooctulosonic acid in intact lipopolysaccharides by spin-echo 13C NMR; Strain SM et al.; The 3-deoxy-D-mannooctulosonic acid (KDO) region of lipopolysaccharides (LPS) from the heptoseless mutant Salmonella minnesota R595 and inner core and heptoseless mutants derived from Escherichia coli K12 was studied by 13C NMR spectroscopy . A spin-echo spectral editing technique was employed for the selective detection of the quaternary anomeric carbon of ketosidically linked KDO . Only two quaternary carbon resonances attributable to KDO were detected in the anomeric carbon spectral region of each LPS from heptoseless mutants E . coli D31m4 (99.7 and 100.8 ppm) and S . minnesota R595 (100.0 and 100.9 ppm) . Integrated signal intensities from fully relaxed normal 13C spectra showed that equivalent molar quantities of KDO and glucosamine (i.e . 2 mol of each) were present in each of these samples . Similarly, only two KDO anomeric carbon resonances were detected in the LPS from the inner core mutants E . coli D21f1 (100.8 and 101.2 ppm) and E . coli D21e7 (100.8 and 101.2 ppm) . These data confirm the presence of a KDO disaccharide structure rather than a trisaccharide as determined by others using thiobarbituric acid-based assays . The LPS of E . coli D21 (complete inner core oligosaccharide) exhibited four quaternary anomeric carbon resonances (99.4, 100.7, 101.8, and 102.7 ppm) . The unequal intensities of these resonances, however, demonstrated that significant heterogeneity exists with respect to KDO substitution in this LPS . A third KDO moiety present in substoichiometric amounts could be consistent with this observation . However, this possibility could not be distinguished from other modes of substitutional heterogeneity involving only 2 KDO residues. Eur J Biochem, 1985 Oct 15, 152(2), 353 - 9 Alterations in rats in vivo of the chemical structure of lipopolysaccharide from Salmonella abortus equi; Freudenberg MA et al.; A biosynthetically double-labelled lipopolysaccharide (LPS) from Salmonella abortus equi was used to study possible in vivo degradation of LPS in rats . The preparation designated rLPS-I was labelled with 3H in the fatty acids and 14C in the sugars . Three days after its intravenous injection the concentration of the two isotopes in the liver was analysed directly by combustion of liver tissue in a sample oxidizer . It was found that compared to the starting LPS, less 3H activity was present than 14C, indicating that partial deacylation had occurred . Reisolation and purification of radioactive material present in the liver revealed that all radioactivity was present in a macromolecular form . Analysis showed that the ratio of the two isotopes was identical to that determined in the starting liver tissue . To exclude the possibility that the loss of 3H might have been due to isotopic dilution the above experiments were repeated with a second LPS preparation (rLPS-II) labelled with 14C in the fatty acids and 3H in glucosamine . Isotopic analysis confirmed that here too a lower content of fatty acids in the LPS was present in the liver . A large-scale (20 rats) reisolation of non-radioactive LPS of S . abortus equi from rat livers three days after injection was carried out . Chemical analysis revealed the presence of 3-deoxy-D-manno-octulosonic acid, heptose, galactose, mannose and rhamnose in a molar ratio similar to that of the original LPS . However a significant reduction in the amount of abequose was found . Fatty acid analysis showed a significant reduction in the content of 3-hydroxytetradecanoic, dodecanoic and hexadecanoic acids, while 2-hydroxytetradecanoic acid was virtually absent . Only the relative amount of tetradecanoic acid was comparable to that of the starting LPS . Biological activity tests on the reisolated material showed a reduced antigenic activity . However, pyrogenicity, lethal toxicity, local Shwartzman-inducing properties and Limulus lysate gelating activity were comparable to the starting S . abortus equi LPS. Am J Physiol, 1985 Oct, 249(4 Pt 2), H715 - 22 Increased myocardial contractility during endotoxin shock in dogs; Kober PM et al.; The slope of the left ventricular (LV) end-systolic pressure-diameter relationship (Ees) was analyzed in open-chest, pentobarbital-anesthetized dogs before and after endotoxin administration . A lead II electrocardiogram, systemic arterial pressure, LV pressure, LV dP/dt, and LV minor axis diameter were measured . After control measurements were taken, dogs were given either 1 mg/kg Salmonella enteritidis endotoxin (n = 5) or an equivalent volume of saline (n = 4) . Control dogs were followed for 240 min . Endotoxic dogs were monitored until death (246 +/- 44 min) . There were no significant changes in Ees in control dogs (17 +/- 3 mmHg/mm), which were hemodynamically stable for 4 h . Ees was significantly increased in endotoxic dogs even into the late stages of shock (41 +/- 11 mmHg/mm, P less than 0.01) . Only during the terminal phase did Ees fall significantly below control (11 +/- 2 mmHg/mm, P less than 0.05) . End-diastolic diameter decreased following endotoxin administration (P less than 0.05) but returned toward control by the terminal stage . Peak + LV dP/dt was depressed following endotoxin injection . Myocardial contractility was not depressed except as a terminal event . Early depression of cardiovascular performance in endotoxic dogs was therefore due to decreased preload and not cardiac dysfunction. J Immunol Methods, 1985 Oct 10, 82(2), 199 - 207 An enzyme-linked immunosorbent assay (ELISA) for the measurement of antibodies to different parts of the gram-negative lipopolysaccharide core region; Appelmelk BJ et al.; Bovine serum albumin was complexed with the core antigens of either Escherichia coli J5 LPS, Salmonella minnesota R595 LPS or E . coli lipid A . These core-BSA complexes were used for solid-phase coating in ELISAs for anti-core antibodies . Antibodies, binding to various parts of the core region were easily quantified in a single experimental set-up, which was hitherto not possible . The ELISA has only 3 incubation steps and is not costly as only moderate amounts of the core antigens (i.e., 1 microgram per test) were needed for coating . The sensitivity proved to be excellent and the complexes were biologically fully active (compared to native, smooth LPS), which make them suitable for the screening (after fusion) of monoclonal anti-core antibodies . Another