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J C Frantz

Publications and source records attributed to J C Frantz.

15 recordsLinked to original sources
PubMed1997

Reactivity with a specific epitope of outer surface protein A predicts protection from infection with the Lyme disease spirochete, Borrelia burgdorferi.

The response to recombinant vaccines for Lyme disease was studied to determine serum antibody levels effective in protecting against tick-transmitted infection. Data presented here demonstrate a significant correlation between antibody to an epitope on outer surface protein A (OspA) and protection against infection with Borrelia burgdorferi in canines and mice. A competitive enzyme-linked immunosorbent assay was developed to measure antibody to a site on OspA, defined by monoclonal antibody LA-2. Comparison of LA-2 titers against infection of canines and mice following vaccination and challenge established a predicted value for LA-2 titers. The statistical relationship between serum antibody levels and protection was calculated by logistic regression analysis. The statistical model predicted that an LA-2 titer of 0.32 microg equivalents (eq) per ml correlated to an 80% predicted probability of protection for both mice and dogs. This value was used to classify mice and dogs as to their protected status at the time of tick exposure. The LA-2 cutoff titer (0.32 microg eq/ml) correctly classified all dogs (n = 13) and mice (n = 44) that failed to become infected. By contrast, 20 of 22 dogs and 28 of 31 mice with titers of less than 0.32 microg eq/ml became infected. On the basis of these results, we conclude that an LA-2 titer is a reliable indicator of immune status for estimating immune protection following use of OspA-based vaccines for B. burgdorferi sensu stricto.

Animals↗
PubMed1995

Incomplete protection of hamsters vaccinated with unlipidated OspA from Borrelia burgdorferi infection is associated with low levels of antibody to an epitope defined by mAb LA-2.

Efforts to develop a recombinant vaccine for Lyme disease have focused on using the outer surface protein A (OspA) of Borrelia burgdorferi as an immunogen. We evaluated the effectiveness of an unlipidated recombinant OspA as a vaccine in hamsters. This molecule is soluble and can be produced in high yield in Escherichia coli, characteristics that permit simple and relatively low cost production. Vaccination with unlipidated OspA protected a substantial portion of animals--59-79%, depending on the challenge strain and route--against moderate doses of spirochetes delivered either by injection or by bite of infected nymphal ticks (Ixodes scapularis). The instances of vaccine failure were associated with development of low levels of antibody to a particular OspA epitope, one defined by mAb LA-2. At least 50 ng ml-1 of LA-2 equivalent antibody was necessary for protection of hamsters. Lower LA-2 equivalent antibody concentrations occurred in unprotected animals in the presence of high-titered polyclonal antibody to native OspA. A competitive binding assay to quantitate this serum fraction is described that should be of use in monitoring the quality of the antibody response to OspA in vaccine trials. Concentrations of LA-2 equivalent antibody parallel the ability of the serum specimens to inhibit the growth of B. burgdorferi in culture.

Animals↗
PubMed1991

Reproductive failure associated with Leptospira interrogans serovar bratislava infection of swine.

Specimens from 17 swine herds experiencing reproductive failure were examined for Leptospira interrogans serovar bratislava. Clinical signs observed in these herds included stillborn pigs, weak neonatal pigs, and abortion. Diagnostic tests used to determine L. interrogans serovar bratislava infection were bacteriologic culture, serologic assays to detect antibodies, and immunofluorescence. Examination of fetal serum for antibodies against serovar bratislava and a fluorescent antibody test were the most practical diagnostic procedures.

Abortion, Veterinary↗
PubMed1991

Effects of purified Pasteurella multocida dermonecrotoxin on the nasal ventral turbinates of fattening pigs: histological observations.

Fattening specific pathogen-free derived pigs were injected intramuscularly with dermonecrotoxin of Pasteurella multocida, capsular type D. Ten days later, the nasal ventral turbinates and liver were examined histologically. A moderate turbinate atrophy was observed due to an increased number of osteoclasts and the absence of intramembranous bone apposition. Liver lesions were limited to some hepatocyte necrosis, sinusoid neutrophil infiltration and Kupffer cell hypertrophy. This study demonstrated that adult pigs are sensitive to P. multocida dermonecrotoxin.

Animals↗
PubMed1991

Atrophic rhinitis caused by Pasteurella multocida type D: morphometric analysis.

In order to study the distribution and the extent of atrophy caused by Pasteurella multocida in the nasal conchae, experimental piglets were injected intramuscularly at seven days of age with either two or four 50% mouse lethal doses per kg body weight of P. multocida type D dermonecrotoxin. Experimental and control piglets were killed four, six and ten days postinjection. Serial transverse paraffin embedded sections of the noses were cut throughout the entire length of the nasal conchae. The area of the nasal ventral conchae was measured and the morphometric index of the nasal cavity was calculated. It was observed that P. multocida type D dermonecrotoxin induced severe atrophy of the nasal ventral conchae. This atrophy was present along the entire conchae. However, it was most severe at the level of the first and second premolar teeth.

Animals↗
PubMed1990

Effects of purified Pasteurella multocida dermonecrotoxin on cartilage and bone of the nasal ventral conchae of the piglet.

The effect of intramuscular injection of purified dermonecrotoxin (DNT) from Pasteurella multocida type D on the nasal ventral conchae of piglets was studied. Severe atrophy of the conchae was observed 4, 6, and 10 days after injection (p.i.d). Lesions were observed in conchae cartilage and bone. Cartilage changes observed were the absence of chondrocyte maturation and hypertrophy, hyaline cartilage invasion by fibroblast-like and multinucleated cells, and endothelium damage with haemorrhages along the cartilage. Intramembranous bone was absent on p.i.d. 4, 6, and 10. Lamellar bone trabeculae were rarefied on p.i.d. 4 and almost absent on p.i.d. 10. Trabeculae were either normal or had the aspect of a dissolved bone matrix, leaving only irregularly oriented collagen fiber bundles. The number of osteoclasts was increased, especially the subperiosteal osteoclasts at the eccentric side of the scrolls. The osteoblasts appeared normal or their cytoplasm was dilated by vacuoles. It is concluded that the macroscopic conchae atrophy results from histological alterations and subsequent loss of both cartilage and bone. Further investigation is necessary to know whether the toxic effect of DNT on cells and matrix is direct or dependent of the vascular damage.

Animals↗
PubMed1989

Effect of vaccination with a bacterin containing Leptospira interrogans serovar bratislava on the breeding performance of swine herds.

Swine herds suspected to be infected with Leptospira interrogans serovar bratislava were vaccinated with bacterins containing 5 or 6 leptospiral serovars in which serovar bratislava was the unique component. The principal diagnostic feature indicating an infection by this organism was demonstration of antibody against serovar bratislava in sera from stillborn pigs. For 1 breeding cycle after vaccination of herds on 3 farms, 255 of 266 (95.9%) sows and gilts given the 6-serovar bacterin farrowed. In contrast, 233 of 311 (74.9%) sows and gilts given the 5-serovar bacterin farrowed. These results, as evaluated by analysis of variance techniques, showed a significant improvement (P less than 0.01) in reproductive performance for groups vaccinated against serovar bratislava.

Animals↗
PubMed1987

Investigation of synthetic Escherichia coli heat-stable enterotoxin as an immunogen for swine and cattle.

In its native form Escherichia coli heat-stable enterotoxin (STa) is nonantigenic; however, neutralizing antibodies are elicited in animals vaccinated with toxin-carrier conjugates. To study the immunogenicity of STa, peptides STa1-18 and STa5-18 were synthesized, characterized, and conjugated to carrier proteins. Pregnant gilts and heifers were hyperimmunized with the respective conjugates. Following parturition neonates were challenged with virulent E. coli (K99+ STa+). Peptides coupled to ovalbumin and emulsified with Freund adjuvant elicited antibodies that neutralized toxin-induced fluid accumulation in suckling mice. Peptides coupled to particulate carriers, with or without muramyl dipeptide adjuvant, failed to induce a measurable response. Peak antibody levels in sera were observed following three doses of conjugate and persisted for several weeks. The serological response in cattle was superior to that observed in swine; however, antibody levels in porcine colostrum were higher than those observed in cattle. Clinical observations of neonates from vaccinated dams indicated that passively obtained antibody provided partial protection from disease, but not as complete as that demonstrable with whole cell bacterins that induce antibody to pili. However, the data suggest the potential for utility of synthetically prepared antigens.

Animals↗
PubMed1986

Synthesis and antigenic activity of E. coli ST and its analogues.

Several enterotoxigenic E. coli (ETEC) are common causes of diarrhea in man and animals. These strains of E. coli produce two types of enterotoxins: heat-stable (ST) and heat-labile (LT). These toxins are peptides of molecular weight 2000 and 90,000 daltons, respectively. It is proposed that the synthetic analogues of these toxins could be effectively used as the vaccines against enterotoxigenic activity of E. coli. In this paper we report the isolation and chemical characterization of a heat-stable toxin STa. We also report the synthesis of this toxin and its analogues and their biochemical and immunological characterization.

Amino Acid Sequence↗
PubMed1984

Binding of Escherichia coli heat-stable enterotoxin to rat intestinal cells and brush border membranes.

The association of heat-stable enterotoxin (STa) produced by enterotoxigenic Escherichia coli 431 with isolated rat intestinal epithelial cells and brush border membranes was characterized. Specific binding of strain 431 125I-STa to a single class of specific high-affinity receptors was saturable and temperature dependent and reached a maximum between 5 and 10 min. A 1,000-fold excess of unlabeled 431 STa competitively displaced 90 to 95% of radiolabeled enterotoxin bound to brush border membranes. In contrast, specific binding of 431 125I-STa to intestinal cells ranged from 40 to 65%. The number of STa-specific receptors on rat intestinal cells determined by Scatchard analysis was 47,520 +/- 14,352 (mean +/- standard error of the mean) per cell, with affinity constants (KaS) of 2.55 X 10(11)and 4.32 x 10(11) liters/mol determined for intestinal cells and brush border membranes, respectively. Villus intestinal cells appeared to possess about twice as many STa receptors as did crypt cells. Dissociation of specifically bound 431 125I-STa from intestinal cells and brush border membranes was minimal (2 to 5%). In addition, neither the rate nor the extent of dissociation was increased by a 1,000-fold excess of unlabeled homologous 431 Sta. Binding experiments with 431 125I-STa and brush border membranes showed that purified unlabeled STas from enterotoxigenic E. coli strains 667 (class 1 porcine enteropathogen), B-41 (bovine enteropathogen), and human strains 213C2 (Mexico) and 153961-2 (Dacca, Bangledesh) exhibited patterns of competitive inhibition similar to those of homologous unlabeled 431 STa (class 2 enteropathogen). A lipid extract which contained gangliosides and glycolipids exhibited dose-dependent competitive inhibition of heat-labile enterotoxin binding to brush border membranes but did not inhibit binding of 431 125I-STa. Purified heat-labile enterotoxin from strain 286C2 did not inhibit binding of 431 STa to brush border membranes. Pronase treatment of brush border membranes reduced binding of 431 125I-STa by about 30%, suggesting that the STa receptor was a protein or a glycoprotein. The putative STa receptor was radiolabeled with 431 125I-STa and solubilized with sodium deoxycholate. One major radioactive band was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by radioautography. These data suggested that STas bind essentially irreversibly to a specific receptor on the cell surface of intestinal cells before activation of guanylate cyclase.

Animals↗
PubMed1983

Chemical properties of heat-stable enterotoxins produced by enterotoxigenic Escherichia coli of different host origins.

Five heat-stable enterotoxins (STs) produced by enterotoxigenic Escherichia coli strains of porcine, bovine, and human host origins have been purified to apparent homogeneity. The STs with biological activity in suckling mice and piglets (STaS) contained 18 amino acid residues, 10 amino acids with a high proportion of acidic amino acids, and 6 half-cystines. The carboxy-terminal and amino-terminal residues of all STaS were tyrosine and asparagine, respectively. All five STa preparations were homogeneous by several criteria: (i) a single symmetrical peak on gel filtration, (ii) a single fluorescent band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, (iii) single carboxyl-terminal and amino-terminal residues, and (iv) amino acid analysis data that indicated a stoichiometric relationship between the component amino acids. The isoelectric points of the five STaS ranged from 3.88 to 4.08. All five purified preparations were heat stable and not denatured by organic solvents, detergents, or treatment at pH 1, but were partially inactivated after incubation at pH 12.0. Biological activity was completely abolished by treatment with reducing and oxidizing agents, which suggested that one or more disulfide bonds play an important role in the mechanism of action of STaS. Antisera raised against strain 431 STa, produced by a porcine class II enterpathogen, neutralized homologous 431 STa as well as heterologous purified STa preparations. The antiserum was used as a reagent in a sensitive radioimmunoassay to detect suckling mouse-positive strains of enterotoxigenic E. coli.

Amino Acids↗
PubMed1983

Chemical and immunological properties of Escherichia coli heat-stable enterotoxin.

Five heat-stable enterotoxins (STs) produced by enterotoxigenic E. coli (ETEC) strains of porcine, bovine and human origin have been purified to apparent homogeneity. The STs with biological activity in suckling mice and piglets (STA) contained 18 amino acid residues, 10 or 11 different amino acids with a high proportion of acidic amino acids and 6 half-cystines. All 5 purified preparations were heat-stable, not denatured by organic solvents and detergents, resisted protease digestion and treatment at pH 1.0, but were partially inactivated by incubation at pH 12.0 and totally inactivated by reducing and oxidizing agents which disrupted disulfide bonds. The isoelectric point (pI) of the 5 STAs ranged from 3.88 to 4.08. Antiserum raised against strain 431 ST, a porcine class II enteropathogen, neutralized all 5 STAs and was useful as a reagent in a sensitive radioimmunoassay to detect suckling mouse positive strains of ETEC.

Amino Acids↗
PubMed1981

Immunological properties of Escherichia coli heat-stable enterotoxins: development of a radioimmunoassay specific for heat-stable enterotoxins with suckling mouse activity.

Antiserum was raised against the purified heat-stable enterotoxin (ST) produced by enterotoxigenic Escherichia coli strain 431, a class II porcine enteropathogen. The antiserum was used to examine the antigenic determinants of STs produced by enterotoxigenic strains of different host origins and develop a sensitive radioimmunoassay specific for ST having biological activity in suckling mice and piglets (STA). The antiserum neutralized one effective dose of toxin at a dilution of 1:5,000 and neutralized approximately 40 microgram of toxin per ml of serum. In the radioimmunoassay, protein A-bearing staphylococci was used as the primary solid-phase adsorbent. The purified STs produced by a class I enteropathogen (strain 667) and by a bovine enterotoxigenic strain (B-41) exhibited patterns of competitive inhibition identical to those of homologous unlabeled strain 431 ST in the radioimmunoassay when specific antibody to strain 431 ST was used. The levels of ST in culture supernatants determined by the suckling mouse assay correlated with the concentrations of toxin measured by the radioimmunoassay. The antiserum was specific for STA produced by enterotoxigenic E. coli of porcine, bovine, and human origins and did not react with heat-labile enterotoxin or with ST that had biological activity in piglets but not in suckling mice (STB). These results suggest that STA molecules having different host origins share at least one antigenic determinant.

Animals↗
PubMed1979

Growth yields and fermentation balance of Bacteroides fragilis cultured in glucose-enriched medium.

Bacteroides fragilis is an obligate anaerobic bacterium classified with the gram-negative, non-sporeforming bacilli and is the Bacteroides species most frequently isolated from human infections. In the present study, experiments were designed to investigate growth characteristics of B. fragilis in a complex medium. In a minimal defined medium, which was employed for comparison purposes, B. fragilis grew with a generation time of 2 h. Growth of the organism in glucose-enriched medium used in the present study was superior. Maximum generation time was 60 min. Total and viable cells (colony-forming units) were 8.9 x 10(9) and 2.1 x 10(9), respectively, at maximum measurable growth. The molar growth yield (Ym) was 51.5. Growth yields were found to reach a maximum 2 to 3 h before maximum growth and to vary with respect to the phase of growth. Estimates of the fermentation products indicated that glucose was the sole energy substrate. Major products included acetic acid, propionic acid, lactic acid, and succinic acid. Other products included ethyl alcohol, pyruvic acid, and fumaric acid. No attempt was made to recover CO2 or formic acid. The OR balances from two experiments were 0.013 and -0.093 and the respective carbon recoveries were 6.268 and 6.241. The results of the present study show that B. fragilis is capable of rapid rates of growth in vitro by using glucose as the sole energy source.

Bacteroides fragilis↗