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PubMed1981

Immune response to parental and rough mutant strains of Salmonella minnesota.

Specificity of immune response to smooth and rough mutant strains of Salmonella minnesota was investigated. Immunization of mice with Rd and Re rough mutants resulted in formation of bactericidal plaque-forming cells directed against the lipopolysaccharide structure of both the mutants and the parental smooth strain. These antibody plaques, however, were not bactericidal for smooth strains of other gram-negative species, i.e., Escherichia coli, Salmonella typhosa, Klebsiella pneumoniae, Shigella dysenteriae, and Pseudomonas aeruginosa. Plaques produced against the smooth strain of S. minnesota or other species were not bactericidal for rough strains. It was concluded that immunization with rough mutants produces bactericidal antibodies directed against the closely related parental strain but not against smooth strains of unrelated bacterial species. The relevance of these observations to the nonspecific protection by rough mutants is discussed.

Animals↗

PubMed1978

Angiotensin-converting enzyme in macrophages and Freund's adjuvant granuloma.

Low angiotensin-converting enzyme (ACE) activity was found in rat and mouse peritoneal macrophages, in rat and rabbit pulmonary alveolar macrophages, in cultured mouse peritoneal macrophages stimulated i.p. for four days by thioglycollate, and in rabbit pulmonary alveolar macrophages stimulated in culture by 0.1 to 100 microgram/ml Salmonella typhosa endotoxin for four days. Rat subcutaneous Freund's adjuvant granulomas induced with Mycobacterium butyricum or M. tuberculosis H37 Ra contianed low ACE activity which was generally lower than that present in control tissues. Increased ACE activity in sarcoidosis and Gaucher's disease lesions does not reflect a universally high synthesis of ACE in mammalian macrophages or granulomas, but may be due to specific mechanisms.

Animals↗

PubMed1998

Reduction of fever by housing in small cages.

Housing conditions influence anatomy, physiology, and behaviour of animals. The aim of this study is to investigate whether the generation of fever, a defence response of the body, is also affected by housing conditions. Golden hamsters (Mesocricetus auratus) were housed in small cages, large cages, or large and enriched cages. After 9 weeks of exposure to their respective environments, the fever response to the administration of lipopolysaccharide (50 micrograms/kg from Salmonella typhosa) was tested. One hundred and twenty experiments in 30 hamsters demonstrated that housing in small cages diminished the fever responses (increase in core temperature and fever index) significantly by approximately 20%, and is likely to be due to a higher stress level. The findings demonstrate that the results of physiological experiments are not only influenced by the experimental design, but also by pre-experimental housing conditions.

Animals↗

PubMed1976

Effect of glass on pH-dependent stability of typhoid vaccine.

Vaccines made from the Ty-2 strain of Salmonella typhosa were tested periodically for stability of pH and of potency. The acetone-treated cultures prepared in buffered saline solutions retained potency beyond 30 months of storage at 0 to 5 C. Similar vaccines in unbuffered saline solutions lost potency coincident with increase of alkalinity. Vaccines packaged in United States Pharmacopeia borosilicate glass vials retained potency and pH stability, whereas those in Type III United States Pharmacopeia soda-lime glass vials were less stable.

Animals↗

PubMed1982

On the pyrogenic action of intravenous lipid A in rabbits.

1. Previous evidence purporting to show that lipid A is the pyrogenic moiety of endotoxin is demonstrably inconclusive. 2. We have extracted lipid A from endotoxin of Salmonella typhosa and tested the pyrogenic action of the lipid A, the residual polysaccharide and the parent endotoxin, by intravenous injection in conscious rabbits. 3. Lipid A dissolved in an aqueous solution of rabbit serum albumin induced a significant pyrexia of short latency, while neither rabbit serum albumin alone, nor the polysaccharide from S. typhosa, affected body temperature. The physical presence in the injectate of the polysaccharide from S. typhosa did not enhance the pyrogenicity of the lipid. 4. Dose-response curves for lipid A and the parent endotoxin, over the dose range 10 ng-20 micrograms, showed that lipid A incorporated in endotoxin was much more pyrogenic than pure lipid A in solution. When separated from the polysaccharide component of endotoxin, lipid A lost more than 99.9% of its pyrogenic activity, at threshold doses.

Animals↗

PubMed1981

Effect of endotoxin on granulation tissue formation in rats.

Open wounds were incised in the dorsal skin of female Wistar rats. Solutions of Salmonella typhosa endotoxin (0.25 micrograms to 25 micrograms/ml saline) were applied 3 times a day on granulation tissue formed in the wounds. 5 days of treatment with the lowest endotoxin concentration resulted in 25% increase of the weight of the tissue, a more than 30% increase of DNA content and a 25% increase of hydroxyproline content in the tissue. Further elevation of these values could be obtained by increasing endotoxin concentration by tenfold or hundredfold but these changes were not very pronounced.

Animals↗

PubMed1995

Diphosphoryl lipid A from Rhodobacter sphaeroides transiently activates NF-kappa B but inhibits lipopolysaccharide induction of kappa light chain and Oct-2 in the B-cell lymphoma line 70Z/3.

Lipopolysaccharide (LPS) is implicated in much of the pathophysiology associated with gram-negative septic shock. One approach to this serious clinical problem is to develop new drugs that antagonize the action of toxic LPS. A model system to study LPS action and test for potential antagonists is readily provided by LPS regulation of the kappa gene in the murine B-cell line 70Z/3. Rhodobacter sphaeroides diphosphoryl lipid A (RsDPLA) effectively blocked toxic LPS induction of kappa light-chain immunoglobulin expression in 70Z/3 cells. Induction of kappa expression by LPS is dependent on the activation of at least two transcription factors, Oct-2 and NF-kappa B. RsDPLA completely repressed the long-term activation of NF-kappa B observed after 24 h of Salmonella typhosa LPS treatment and antagonized activation of oct-2 mRNA expression. However, RsDPLA was not an inert competitor of LPS. RsDPLA alone strongly activated NF-kappa B binding activity by 30 min but not beyond 9 h of treatment. It also induced a small increase in oct-2 mRNA levels. RsDPLA is not simply a weak agonist; we found no graded increase in kappa expression with increasing RsDPLA concentrations up to 50 micrograms/ml. The NF-kappa B complexes activated by RsDPLA and S. typhosa LPS were both composed of the p50-p65 heterodimer. These results suggest that the physiological LPS receptor(s) on B cells transmits qualitatively different signals depending on the nature of the binding ligand and that the fatty acyl groups of LPS play an important role in activating signal transduction.

Animals↗

PubMed1978

Biologic properties of bacterial lipopolysaccharides treated with chromium chloride.

Addition of small amounts of chromium chloride to a saline suspension of Salmonella typhosa lipopolysaccharide (LPD; Difco) caused a marked reduction in several of the biologic activities of this substance including toxicity, B-cell mitogenicity, plasma colony-stimulating activity (CSA), radioprotective effect, and induction of the dermal Shwartzman reaction. Nevertheless, LPS treated with chromium chloride was found to be at least as effective as untreated LPS in enhancing resistance of B6CBF1 mice to the lethal effects of Klebsiella pneumoniae infection.

Adjuvants, Immunologic↗

PubMed1980

Contrasting roles of 5-hydroxytryptamine and noradrenaline in fever in rats.

1. We have investigated the effects of endogenous monoamine depletion on the development of fever in rats. 2. Fever was produced in rats by a single intraperitoneal injection of Salmonella typhosa endotoxin or leucocyte pyrogen manufactured from ox blood. 3. Depletion of brain 5-hydroxytryptamine (5-HT) by pretreatment with p-chlorophenylalanine prevented the rise in rectal temperature produced both by bacterial endotoxin and by leucocyte pyrogen. 4. On the other hand depletion of noradrenaline (NA) by 6-hydroxydopamine pretreatment resulted in a potentiation of the fever produced by bacterial endotoxin. 5. These results suggest that 5-HT is involved in mechanisms responsible for the rise in temperature during fever and that NA is involved in mechanisms which serve to attenuate the rise.

Animals↗

PubMed1998

Fever in goldfish is induced by pyrogens but not by handling.

Six goldfish, Carassius auratus, weighing 2.5 to 4 g were placed individually in an aquarium with two communicating chambers. One chamber was thermostatted at 34 degrees C, the other at 37 degrees C. In control Session a, without external intervention, fish selected the cooler chamber most of the time and stayed only 4.8 +/- 1.1 min/2 h at 37 degrees C. In Session b, infectious fever was assayed: pyrogen (Salmonella typhosa LPS, or human interleukin-2) was injected intracranially and fish stayed 44.7 +/- 15.3 min/2 h at 37 degrees C. In Session c, behavioral stress was achieved by chasing the fish with a net, catching it, handling it out of water, and injecting 10 microL of saline intracranially. Fish stayed 2.7 +/- 1.0 min/2 h at 37 degrees C. Analysis of variance showed that stay at 37 degrees C was significantly longer in Session b than a and c, and that Sessions a and c were not significantly different from one another. This result confirms the existence of behavioral fever, but does not support the hypothesis of fever in fish after handling.

Acclimatization↗

PubMed1979

Studies on the mechanism of haemopoietic stem cell (CFUs) mobilization. A role of the complement system.

A variety of substances can mobilize haemopoietic stem cells (CFUs) into the peripheral blood. In this study the involvement of the complement system in the mobilization process was investigated. Pretreatment of mice with the complement-activating factor of cobra venom (CoF), which lowered the serum C3 levels to 10-25% of the normal value, could completely prevent CFUs mobilization induced by high doses of CoF, endotoxin (ET) from Salmonella typhosa, inulin, zymosan and the proteolytic enzymes proteinase and trypsin. On the other hand, mobilization induced by the polyanions dextran sulphate and the copolymer of polymethacrylic acid and styrene could not be prevented, or at least affected only slightly. There appears to be a relationship between the extent of decomplementation by CoF and the extent of CFUs mobilization induced by ET. The results indicate that certain agents mobilize CFUs via the complement system, whereas other agents induce CFUs mobilization independent of the availability of complement components.

Animals↗

PubMed1966

Genetic analysis of the ViA-his chromosomal region in Salmonella.

Johnson, E. M. (Walter Reed Army Institute of Research, Washington, D.C.), Barbara Krauskopf, and L. S. Baron. Genetic analysis of the ViA-his chromosomal region in Salmonella. J. Bacteriol. 92:1457-1463. 1966.-The relative chromosomal location of the ViA determinant, a gene required for Vi antigen expression in Salmonella typhosa (and present also in S. typhimurium), was examined in S. typhimurium x S. typhosa matings. The position of this gene was determined with respect to the histidine (his) and methionine (metG) biosynthesis markers, and to the genetic determinants of somatic antigens 5 (O-5) and 4 (O-4) of S. typhimurium. The gene order established by analyses of the hybrid classes resulting from the genetic crosses was ViA-O-5-metG-O-4 (his). This order suggests that neither ViA nor O-5 is a member of the complex of functionally related structural genes which constitute the O-4 locus. It allows for the possibility, however, of a functional relationship between the genes of the ViA and O-5 loci.

Antigens↗

PubMed1988

Ocimum sanctum--a preliminary study evaluating its immunoregulatory profile in albino rats.

A methanol extract and an aqueous suspension of Ocimum sanctum leaves were investigated for their immunoregulatory profile to antigenic challenge of Salmonella typhosa and sheep erythrocytes by quantifying agglutinating antibodies employing the Widal agglutination and sheep erythrocyte agglutination tests and E-rosette formation in albino rats. The data of the study indicate an immunostimulation of humoral immunologic response as represented by an increase in antibody titre in both the Widal and sheep erythrocyte agglutination tests as well as by the cellular immunologic response represented by E-rosette formation and lymphocytosis. The results of the study indicate an immunostimulant capability for Ocimum sanctum which may be contributory in explaining the adaptogenic action of the plant.

Adjuvants, Immunologic↗

PubMed1983

Immunization with rough mutants of Salmonella minnesota. IV. Protection by antisera to O and rough antigens against endotoxin.

The protection by antisera to O antigens and antigens (lipid A, the Re 595 mutant of Salmonella minnesota, and the J5 mutant of Escherichia coli) of the core portion of endotoxin against lethal challenge with lipopolysaccharide (LPS) was compared. Rabbits immunized with the Re mutant developed antibody that protected mice against challenge with S. minnesota or Salmonella typhosa LPS. Antisera to heterologous O antigen and lipid A were not protective, whereas homologous antisera and antiserum to the Re or J5 mutant protected against lethal challenge. On a volumetric basis, O-specific antiserum was consistently somewhat more protective than antiserum to the Re mutant, which was slightly more protective than antiserum to the J5 mutant. When comparisons were made using passive transfer to similar quantities of hemagglutinating or precipitating antibody, antiserum to the Re mutant was considerably more protective than O-specific antiserum. This greater protection is hypothesized to result from more effective masking of the toxic lipid A moiety by antibody to the rough mutants than by O-specific antibody.

Animals↗

PubMed1998

"Biphasic" fevers often consist of more than two phases.

This paper disproves the common belief that all doses of lipopolysaccharide (LPS) that are commonly referred to as biphasic fever inducing (>/=2 microg/kg) cause truly biphasic responses. A catheter was implanted into the right jugular vein of several strains of adult male rats, and the animals were habituated to the experimental conditions. At an ambient temperature of 30.0 degrees C, loosely restrained animals were injected with a 10 microg/kg dose of LPS (various preparations), and their colonic (Tc) and tail skin temperatures were monitored (from >/=1 h before to >/=7 h after the injection). The results are presented as time graphs and phase-plane plots; in the latter case the rate of change of Tc is plotted against Tc. In experiment 1 the intravenous injection of LPS (from Escherichia coli 0111:B4, phenol extract) into the rats (Bkl:Wistar) induced a triphasic febrile response, as is obvious from time graphs of Tc (3 peaks), time graphs of effector activity (3 waves of tail skin vasoconstriction), and phase-plane plots (3 complete loops); the injection of saline (control) induced no Tc changes. We analyzed whether the triphasic pattern was due to some peculiarities of the experimental design, i.e., the pyrogen preparation used (experiment 2) or the rat strain tested (experiment 3) or whether this pattern reflects a more general law. In experiment 2 we used the same (phenol) preparation of different LPS (from Shigella flexneri 1A and Salmonella typhosa) and a different preparation (TCA extract) of the same LPS (E. coli). Regardless of the LPS used, rats of the Bkl:Wistar strain responded to the 10 microg/kg dose with the triphasic fever. In experiment 3, rats of other strains [Bkl:Sprague-Dawley and Sim:(LE)fBR(Black-hooded)] were tested. Again, all animals responded to the 10 microg/kg dose of E. coli LPS (phenol extract) with the triphasic fever. Because all fevers caused by four different LPS preparations in three rat strains were triphasic, the triphasic pattern is likely to constitute an intrinsic characteristic of the febrile response.

Activity Cycles↗

PubMed1999

Comparison of six dose-response models for use with food-borne pathogens.

Food-related illness in the United States is estimated to affect over six million people per year and cost the economy several billion dollars. These illnesses and costs could be reduced if minimum infectious doses were established and used as the basis of regulations and monitoring. However, standard methodologies for dose-response assessment are not yet formulated for microbial risk assessment. The objective of this study was to compare dose-response models for food-borne pathogens and determine which models were most appropriate for a range of pathogens. The statistical models proposed in the literature and chosen for comparison purposes were log-normal, long-logistic, exponential, beta-Poisson and Weibull-Gamma. These were fit to four data sets also taken from published literature, Shigella flexneri, Shigella dysenteriae, Campylobacter jejuni, and Salmonella typhosa, using the method of maximum likelihood. The Weibull-gamma, the only model with three parameters, was also the only model capable of fitting all the data sets examined using the maximum likelihood estimation for comparisons. Infectious doses were also calculated using each model. Within any given data set, the infectious dose estimated to affect one percent of the population ranged from one order of magnitude to as much as nine orders of magnitude, illustrating the differences in extrapolation of the dose response models. More data are needed to compare models and examine extrapolation from high to low doses for food-borne pathogens.

Food Microbiology↗

PubMed1992

LPS activation of bone marrow natural suppressor cells.

Lipopolysaccharide (LPS) from Salmonella typhosa was injected into C57B1/6 mice and the effect on bone marrow (BM) natural suppressor (NS) cell activity was examined. It was shown that injection of LPS, as low as 0.01 microgram/g body weight, could enhance BM NS activity. The enhanced activity was apparent 24 hr postinjection, and returned to normal by Day 5. It was necessary to show that the enhanced suppression displayed characteristics of NS cells. The suppressor cell is Thy negative and can be found in low density Percoll fractions. Suppression was dependent upon interferon-gamma and could be augmented by lymphokines that were contained in the supernatant of TH2 helper cell. The data suggest that BM NS activity may be influenced in vivo during gram-negative sepsis.

Animals↗

PubMed1985

Fever and survival in aged mice after endotoxin challenge.

Male C57BL/6 mice of 12, 19, and 24 months of age received injections of low (25 micrograms 100 g-1 body weight) or high (50 micrograms 100 g-1 body weight) doses of Salmonella typhosa endotoxin and were exposed to ambient temperatures below (24 degrees C) or within (30 degrees C) the thermoneutral zone. Old mice (19 and 24 months) developed initial fevers followed by hypothermia in response to endotoxin challenge at 24 degrees C, irrespective of dose; 12-month-old-mice became hypothermic at 24 degrees C following injection of the high dose of endotoxin only. At 30 degrees C, 12- and 19-month-old mice developed and maintained fever over 4 hr in response to endotoxin compared with the 24-month-old mice who were unable to maintain fevers. Logistic regression analysis showed that age, ambient temperature, and body temperature responses were significant predictors of survival outcome in endotoxin-treated mice; of these, age and ambient temperature had the strongest effects.

Aging↗