SEARCH · PubMed Health

Results for “Lethal Dose 50”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed1977

Bacteriological and histopathological evaluation of guinea pigs after infection with Listeria monocytogenes.

Randomly bred guinea pigs were infected with Listeria monocytogenes using the intracardial, intravenous and intraperitoneal routes of infection. Doses of Listeria ranged from 5 to 1,000 x the 50% lethal dose based on the 50% lethal dose for intracardially injected Listeria. A complete necropsy was performed on all animals that died after infection. Gross and microscopic examination of tissues revealed major pathological features which include myocarditis, edema and congestion with interstitial pneumonitis present in the lungs, and fatty hepatic changes with focal necrosis. For all or a majority of the animals, large numbers of Listeria were likewise recovered from these organs and from lymph nodes, spleen, kidneys, and adrenal gland tissue. Of the three routes of infection used, guinea pigs were most susceptible to Listeria injected via the intracardial route. The relatively high lethal dose of listeric for the quinea pig, however, suggests that the organism is a low-grade pathogen for this species.

Animals↗

PubMed1978

Intraintestinal toxin in infant mice challenged intragastrically with Clostridium botulinum spores.

Conventionally raised suckling mice were injected intragastrically with 10(5) spores of a Clostridium botulinum type A culture. Botulism was not observed, but 80% or more of mice challenged when 8 to 11 days old had botulinum toxin in the large intestine 3 days later. Mice younger than 7 days or older than 15 days were resistant to the challenge. When in vivo toxin production was started by spores given to 9-day-old mice, toxin was present in the intestine at 1 through 7 days postchallenge but with greatest consistency between 1 and 4 days. Total toxin in an intestine ranged up to 1,920 50% lethal doses as titrated intraperitoneally in adult mice. The dose infecting 50% of a group of 9-day-old mice was 700 (95% confidence limits of 170 to 3,000) spores per animal. Toxin was formed in the lumen of the large intestine; it was not associated with the ileum. Injection of 10(5) spores intraperitoneally into 9-day-old mice resulted in toxin production in the large intestines of 30% of the test animals.

Animals↗

PubMed1979

Resistance to Listeria monocytogenes in mice: genetic control by genes that are not linked to the H-2 complex.

After mice of several inbred strains were injected with Listeria monoyctogenes, two parameters of resistance, the 50% lethal dose and the suppression of bacterial proliferation in spleen, were determined. The strains of mice tested could be segregated into two groups: the resistant C57BL/10Sn mice and the sensitive A/J and DBA/2J mice. Congenic resistant strains of mice were used because they would express the H-2 haplotype of the sensitive strains (H-2a or H-2d) on the background of a resistant strain, C57BL/10Sn. Both the B10.A/SgSn (H-2a) and the B10.D2/Sn (H-2d) mice were as resistant as mice from their background strain and were significantly more resistant than the strains that donated their H-2 locus (A/J or DBA/2J). Therefore, the resistance of mice to Listeria, although genetically controlled, is not controlled by gene (s) linked to the H-2 haplotype. On the other hand, the level of specific immunity to listeria antigens (as indicated by the footpad reaction) was higher in the C57BL/10Sn (H-2b) mice than in either the A/J and B10.A/SgSn (H-2a) mice or the DBA/2J and B10.D2/Sn (H-2d) mice. This observation suggests an H-2 linkage of specific immunity to Listeria.

Animals↗

PubMed1979

Mouse protection test for group B Streptococcus type III.

The mouse model has been used previously for the study of protection against challenge with strains of group B Streptococcus types Ia, Ib, and Ic, but investigators have not yet been successful in causing lethal disease when type III strains are inoculated. In this study, six clinical isolates belonging to serotype III were lethal in seven-week-old outbred albino mice; the 50% lethal dose (LD50) for mice tested ranged from 1.8 x 10(4) to 4.6 x 10(6). In contrast, a laboratory prototype strain of serotype III was not lethal. The lethality observed with this protection test depended on both the volume of the inoculum given and the medium in which the streptococci were suspended. LD50 values decreased as the volume of the inoculum, given intraperitoneally, increased, up to a volume of 1.5 ml. Hyperimmune rabbit antiserum to a clinical isolate of type III protected mice against an estimated 90% lethal dose of the isolate. Normal rabbit serum and heterologous antisera, except for one of two antisera to type Ia organisms, were not protective. Absorption of type III antiserum with whole organisms of serotype III or with purified, type III-specific polysaccharide inhibited protection of mice against type III organisms.

Absorption↗

PubMed1978

Comparison of the toxicities of patulin and patulin adducts formed with cysteine.

The toxicities of patulin and of the patulin adducts formed with cysteine were compared using the mutation-sensitive strain Escherichia coli W3110 thy polA1 and its polA1+ revertant. The acute toxicities of patulin and of the adduct mixture were also compared using NMRI mice. The adduct mixture was shown by thin-layer chromatography to consist of one ninhydrin-positive, one ninhydrin- and MBTH (3-methyl-2-benzothiazolinone hydrazone)-positive, three MBTH-positive, and two ninhydrin- and MBTH-negative components. The results showed that patulin was over 100 times more toxic to E. coli than the adduct complex. Neither patulin nor the adduct mixture was found to induce the repair effect in E. coli. In the mouse feeding tests, the oral 50% lethal dose for patulin was 29 mg/kg, while that of the adduct mixture was greater than 2,370 mg/kg.

Animals↗

PubMed1979

Enzyme-linked immunosorbent assay for detection of Clostridium botulinum type E toxin.

The enzyme-linked immunosorbent assay using the "double-sandwich" technique was utilized to determine Clostridium botulinum type E toxin. With this technique, about 80 mouse intraperitoneal 50% lethal doses of toxin could be detected. Cross-reaction was hardly observed with C. botulinum type A and B toxins. No cross-reaction was observed with culture supernatants of C. botulinum type C or other Clostridium strains. In all probability this was due to the high specificity of the antiserum prepared aginst the toxic component of type E toxin.

Animals↗

PubMed1978

Pseudomonas ribosomal vaccines: preparation, properties, and immunogenicity.

The preparation, properties, and immunogenicity of ribosomal vaccines from Pseudomonas aeruginosa are described. These preparations, containing protein and RNA, were tested for immunogenicity by active immunization of mice and subsequent challenge with homologous, live bacteria. The results demonstrated that vaccines prepared from a majority of serotypes used were immunogenic, i.e., afforded 60 to 100% mouse protection against a challenge inoculum containing 8 to 50 50% lethal doses. In some cases vaccine doses as low as 1 microgram of RNA provided 100% mouse protection. Molecular sieve chromatography of a highly immunogenic ribosomal preparation on Sepharose 4B demonstrated the presence of two molecular weight fractions: (i) peak A, an excluded peak (thus having a molecular weight of at least 2 times 10(7)), and (ii) peak B, considerably retarded, with an elution position corresponding to a molecular weight of about 2.2 X 10(6), approximating that of typical 70S ribosomes. Both peaks A and B were immunogenic; however, the immunogenicity of peak A was greater (i.e., a smaller immunizing dose was required) than that of peak B. Peak A was shown to contain components of lipopolysaccharide in addition to protein and RNA (which comprised 80% of the dry weight of peak A). On the other hand, peak B was shown to be free of lipopolysaccharide, and 100% of its dry weight consisted of protein and RNA.

Animals↗

PubMed1978

Some properties of beta-toxin produced by Clostridium perfringens type C.

Purified beta-toxin from Clostridium perfringens type C was found to be a single polypeptide chain protein with a molecular weight of approximately 30,000. The toxin was heat labile, with 75% of its activity being inactivated by incubation at 50 degrees C for 5 min. Biological activity of the purified toxin was completely destroyed on exposure to trypsin for 30 min at 37 degrees C. The 50% lethal dose for mice was 1.87 microgram of purified toxin.

Animals↗

PubMed1979

Effects of cannabinoids on host resistance to Listeria monocytogenes and herpes simplex virus.

Previous investigations from our laboratories have demonstrated that cannabinoids possess immunosuppressive properties. The present studies were designed to determine whether these agents decrease host resistance to infections with Listeria monocytogenes and herpes simplex virus type 2. Host resistance was measured by changes in the 50% lethal dose of the pathogen in cannabinoid-treated and control mice. The effect of cannabinoids on resistance to L. monocytogens was dose dependent. Delta-9-tetrhydrocannabinol at doses of 38, 75, and 150 mg/kg suppressed resistance to infection by 10-, 17-, and 657-fold, respectively. Marijuana extract was less active but significantly reduced resistance to L. moncytogenes at all tested doses. Resistance to systemic herpes simplex virus type 2 infection was decreased 96-fold by delta-9-tetrahydrocannabinol, although marijuana extract was inactive. The doses and regimen of treatment with cannabinoids that produced significant decreases in host resistance were similar to those which caused suppression of delayed-type hypersensitivity to sheep erythrocytes. The possible mechanisms and public health aspects of the decreased host resistance produced by marijuana extract and its cannabinoids are discussed.

Animals↗

PubMed1979

Enterochelin (enterobactin): virulence factor for Salmonella typhimurium.

The ability of Salmonella typhimurium to synthesize enterochelin (enterobactin; ENT) affects its capacity to grow both in vivo and in vitro. An ENT mutant (96-1), blocked in the conversion of chorismate to 2,3-dihydroxybenzoate, was derived from SR-11, a strain of high mouse virulence. This mutant was unchanged in the other characteristics tested: colonial, biochemical, antigenic, and cellular. In contrast to SR-11, growth of this mutant in complement-inactivated human serum was strongly inhibited. However, addition of 5 muM ENT to the cultures relieved their inhibition. Viable counts of bacteria injected into the mouse peritoneal cavity showed that without ENT, growth of 96-1 was inhibited markedly; with ENT, the apparent growth rate of 96-1 exceeded that of SR-11. The 50% lethal dose (LD50) of 96-1 was 2 to 3 log units higher than that of SR-11. When ENT was injected, the ENT- mutant exhibited an ENT-dose-related decrease in its LD50. A single injection of 300 micrograms of ENT per mouse with the inoculum reduced the LD50 of 96-1 to that of the wild-type strain. These findings support the contention that ENT is a virulence factor for S. typhimurium.

Ascitic Fluid↗

PubMed1979

Passage of Pseudomonas aeruginosa in compromised mice.

There was no appreciable increase in the virulence of Pseudomonas aeruginosa PAO-1 after six passes through infections in mice. When strain PAO-1 was passed through mice compromised with iron and methotrexate, the virulence of the passed bacteria increased for normal as well as compromised mice. Bacteria harvested from intraperitoneal passage in compromised mice were more virulent than bacteria harvested from intrathoracic passage. These bacteria expressed 50% lethal dose values distinctive of the respective bacterial isolate when injected intraperitoneally, intrathoracically, or intravenously. Differences between bacteria from intraperitoneal and intrathoracic passage were apparently due to differences in the selective pressures in the two sites of infection, because the intrathoracically passed bacteria assumed the virulence characteristics of the intraperitoneally passed bacteria after intraperitoneal passage in compromised mice.

Animals↗

PubMed1978

Protective effects of a supernatant factor from Salmonella typhimurium on Salmonella typhimurium infection of inbred mice.

A supernatant factor prepared from 48-h cultures of Salmonella typhimurium has been used to immunize mice against subsequent challenge with normally lethal doses of S. typhimurium. The mouse strains used, C57BL and BALB/c, were sensitive to S. typhimurium with 50% lethal doses of less than 50 organisms. Two doses of supernatant factor, given intraperitoneally 20 days apart, protected mice against a subcutaneous challenge dose 10 days later of 100 50% lethal doses of S. typhimurium, resulting in 50 to 80% survival. The viable counts were reduced initially in organs of immunized mice compared with controls, and the multiplication of bacteria was delayed, although the final levels found in the organs would normally have been lethal. Protection obtained was specific for S. typhimurium in that no increased survival was shown after Salmonella enteritidis challenge of immunized mice. Although lipopolysaccharide was demonstrated in the supernatant factor, lipopolysaccharide alone did not protect challenged mice. Supernatant factor produced delayed-type hypersensitivity reactions in mice sensitized with nonlethal doses of Salmonella. The nature of the active factor, found to be partially protein, has yet to be elucidated.

Animals↗

PubMed1978

Biological and physicochemical characteristics of four serotypes of Salmonella enteritidis.

Four serotypes of Salmonella enteritidis, Anatum ATCC 9270, Newbrunswick ATCC 1608, Oranienburg 200 E, and Pullorum RM, were studied to determine biological, chemical, or physical differences which might explain variations in Salmonella virulence as previously reported by McCullough and Eisele (J. Infect. Dis. 88:278-289, 1951; 89:259-265, 1951). These investigators found that serotype Pullorum was significantly less virulent than serotypes Newport, Derby, Barielly, Meleagridis and Anatum when fed to healthy humans. Results of our own experiments showed that serotype Pullorum RM had a generation time approximately twice that of serotype Anatum 9270. The volume of serotype Pullorum was approximately one-half the volume of the other serotypes used (Anatum 9270, Newbrunswick 1608, Oranienburg 200 E, Cubana 12007, and Meleagridis DR). The number of cells required to yield 1 g dry weight was substantially higher for serotype Pullorum RM than for serotypes Anatum 9270, Newbrunswick 1608, and Oranienburg 200 E. The yield of endotoxin per gram dry weight for serotype Pullorum RM averaged 22 mg/g, whereas yields of endotoxin for serotypes Anatum 9270, Newbrunswick 1608, and Oranienburg 200 E averaged 32 to 35 mg/g. The relative abundance of the four major fatty acids (measured by gas chromatography) also showed distinct differences among the serotypes. Pullorum RM contained less lauric and 3-hydroxymyristic acids and more myristic and palmitic acids than the other three serotypes. The identity of 3-hydroxymyristate was confirmed by mass spectroscopy. Serotype Pullorum RM required 10 times more lipopolysaccharides (endotoxin) to obtain a 50% lethal dose in mice than the other three serotypes. When the lipid part was separated from the polysaccharide and solubilized with bovine serum, the 50% lethal dose of serotype Pullorum RM was equal to that of the other three.

Endotoxins↗

PubMed1979

Effects of BCG infection on the susceptibility of mouse macrophages to endotoxin.

Mice infected intravenously with Mycobacterium bovis (BCG) are 100 to 1,000 times more sensitive to the lethal effects of bacterial lipopolysaccharides (LPS). Since BCG infection results in macrophage activation and LPS may cause pathophysiological effects through interaction with this cell type, it was of interest to determine whether macrophages from BCG-infected animals were more susceptible to the toxic effects of LPS in vitro. When LPS-susceptible, C57BL/6 mice were infected with BCG, a significant reduction in the 50% lethal dose of LPS was first observed after 7 days and persisted for several weeks. Macrophages from these animals had greatly increased susceptibility to LPS in vitro, which correlated with the development of acquired cellular resistance as determined by their ability to inhibit the growth of Listeria monocytogenes. In contrast, BCG infection of C3H/HeJ mice, a strain resistant to LPS, did not alter the 50% lethal dose of LPS for these animals or increase the sensitivity of their peritoneal macrophages to LPS in vitro. These results indicate that susceptibility of BCG-infected mice to the lethal effects of LPS parallels the susceptibility of their macrophages in vitro; release of vasoactive substances from LPS-susceptible activated macrophages in vivo may be, in part, responsible for lethality.

Animals↗

PubMed1979

Mucosal defenses against Salmonella infection in the mouse.

Specific pathogen-free ICR (Institute of Cancer Research) mice were challenged with Salmonella orally, aerogenically, or parentally 24 hr after they received sublethal whole-body irradiation. The early growth for the sublethal inoculum was identical in irradiated and control mice. In the irradiated group, Salmonella multiplied in the liver and spleen until death of the host. Increasing the dose of irradiation reduced the size of the mean lethal dose for the intravenous, intraperitoneal, and aerogenic challenges. However, in the orally challenged mice, the 50% lethal dose dropped only 100-fold when the radiation was increased from 0 to 400 rad, with little further decrease even when the dose was increased to 800 rad. Presumably, the local gut defenses were responsible for this considerable disparity in the lethal effects of an oral vs. parenteral challenge. No evidence was found for enhanced local infection of the gut or increased involvement of the gut-associated lymphoid organs in the irradiated host. The increased mortality seen in the irradiated group seemed to be associated with a continued unrestricted growth of Salmonella in the liver and spleen when the number of peripheral blood leukocytes was at a minimum. Resistance to the sublethal salmonella challenge was eventually restored as the total counts of white blood cells returned to normal.

Administration, Oral↗

PubMed1978

Requirement for macrophages for interferon to be effective against encephalomyocarditis virus infection of mice.

Suppression of macrophages in mice by treatments with silica or auro-thiomalate (Myocrisin) reduced production of serum interferon by polyriboinosinic acid:polyribocytidylic acid by 85 to 90%, indicating that this double-stranded polynucleotide caused interferon production primarily in macrophages. Suppression of macrophages in mice by silica or Myocrisin treatment did not significantly affect the susceptibility of mice to encephalomyocarditis virus, although at virus doses around 20 times the 50% lethal dose they died about 48 h earlier. Macrophage interferon protected mice from encephalomyocarditis virus infection at much lower doses than fibroblast interferon, and treatment of mice with silica or Myocrisin abolished the protection conferred by macrophage interferon, whereas these treatments had a much smaller effect on the protection afforded by fibroblast interferon. The requirement for macrophages for interferon to be effective in mice can explain why macrophage suppression can cause normally nonlethal viruses to kill adult mice.

Animals↗

PubMed1978

Relationship between gentamicin susceptiblity criteria and therapeutic serum levels for Pseudomonas aeruginosa in mouse infection model.

In this study estimations of in vivo and in vitro gentamicin susceptibility for a series of strains of Pseudomonas aeruginosa were compared. The series included an extremely susceptible strain, typically susceptible strains by current susceptibility criteria, and strains with enzymatic and permeability-mediated resistance. In vivo testing was done by using a mice protection test involving six 1-h doses of gentamicin and an inoculum of 50 50% lethal doses of P. aeruginosa. Both normal mice and cyclophosphamide-treated mice were used. It was found that peak serum levels and serum levels of gentamicin obtained just prior to the sixth dose (fifth dose trough levels) required for protection were much higher than minimal inhibitory concentrations (MICs) or minimal bactericidal concentrations (MBCs) obtained in high-cation medium. However, first dose trough levels were similar to MICs or MBCs. Only an extremely susceptible strain, 280, could be treated at antibiotic dosages and serum levels which are considered likely to be safe in humans. A distinct inoculum effect was found in the mice tests, with a 10-fold increase in inoculum producing a 4-fold increase in the amount of gentamicin required, but no inoculum effect was found for MICs. These results suggest that current susceptibility criteria in use for gentamicin and P. aeruginosa overestimate gentamicin susceptibility, particularly when low-cation growth medium is used for susceptibility testing and when treating disseminated infection.

Animals↗

PubMed1977

Immunization with Shigella dysenteriae type 1: evaluation of antitoxic immunity in prevention of experimental disease in rhesus monkeys (Macaca mulatta).

The role of serum antitoxic antibody in protection against the dysentery caused by Shigella dysenteriae type 1 (Shiga's bacillus) was studied in monkeys fed 10(10) virulent organisms after parenteral immunization with a formalin-inactivated Shiga toxoid preparation standardized in mice. Two 125-microgram doses of toxoid adsorbed on aluminum hydroxide adjuvant and given 14 days apart provided mice with a 54-fold increase in resistance to parenteral toxin. In rhesus monkeys (Macaca mulatta), the same regimen of toxoid permitted the safe parenteral administration of toxin in incremental doses ranging from 100 to 1,000 mouse 50% lethal doses and resulted in correspondingly high titers of antitoxin in serum. Nevertheless, the immunized monkeys responded to orally administered Shiga bacilli by development of diarrhea and dysentery that was as severe as (or more severe than) the response of unimmunized controls. The failure of extraordinarily high levels of circulating antibody to protect against experimental shigellosis suggests that the intestinal mucosal sites of toxinmediated response are beyond the reach of systemic antitoxin.

Animals↗