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Biomedical subjects

C R Young

Publications and source records attributed to C R Young.

101 records · Page 6Linked to original sources

Genetic control of the immune response to ferritin in mice.

The immune response to the antigen horse spleen ferritin was tested in sixteen inbred strains of mice. Using a fixed antigen percentage bound isotope technique, it was found that the quantity of antibody produced was related to the genetic status of the responding animal. A continuous distribution of responses was obtained, which were found to be linked to H-2 loci and the 2 non-H-2 loci 'Tla' and 'Theta' and these responses are detectable following primary immunization. It is suggested that the continuous distribution of quantitative antibody responses to ferritin, is compatible either with a large number of IR-genes or with a cross tolerance hypothesis requiring no IR-genes at all.

Analysis of Variance↗

Codominant inheritance in immunogenetic (IR-gene) systems.

Immunogenetic (IR-gene) systems consist of animals showing different quantitative antibody responses when immunized with similar doses of a given antigen. Strains of animals giving high and low antibody titres are described as high and low responders, respectively. The degree of dominance in F1 hybrid strains, obtained from a cross between high and low responder parents, can readily be calculated using the dominance index formula, which takes the value of +1 for complete dominance, -1 for complete recessivity and the value of zero for no dominance. In reviewing 1527 F1 animals, obtained from ninety-one immunogenetic systems, the degree of diminance (d) was found to be: +0-0076 +/- 0-1053 (mean +/- s.e.), which is close to a value of zero and this is consistent with codominant inheritance. It is suggested that in immunogenetic systems, both alleles are expressed as codominant genes.

Animals↗

Properties of drug-containing spherical pellets produced by a hot-melt extrusion and spheronization process.

The objectives of this study were to investigate the particle size distribution, morphology and dissolution properties of spherical pellets produced by hot-melt extrusion and spheronization and to compare the properties of hot-melt extruded pellets with beads manufactured by a traditional wet-mass extrusion and spheronization method. Spherical pellets were produced by hot-melt extrusion without the use of water or other solvents. A powder blend of theophylline, Eudragit Preparation 4135 F, microcrystalline cellulose and polyethylene glycol 8000 was hot melt-extruded and the resulting composite rod was cut into cylindrical pellets. The pellets were then spheronized in a traditional spheronizer at an elevated temperature. The same powder blend was processed using conventional wet-mass techniques. Unlike wet-mass extruded pellets, pellets prepared from hot-melt extrusion displayed both a narrow particle size distribution and controlled drug release in dissolution media less than pH 7.4. Scanning electron microscopy, X-ray diffraction and porosity measurements were employed to explain the differences in drug release rates of theophylline from pellets produced by the two processing techniques. Theophylline release from the hot-melt extruded pellets was described using the Higuchi diffusion model, and drug release rates from wet-granulated and melt-extruded pellets did not change after post-processing thermal treatment.

Biocompatible Materials↗

Complications of reperfusion in acute aortic artery occlusion following saddle embolization originating from an atrial myxoma.

A 58-year-old man presented to the hospital with an 8-hour history of acute-onset bilateral lower limb ischemia. A large saddle embolus had occluded the aorta and could not be removed by balloon endarterectomy through the femoral arteries. Successful open aortic and femoral thromboembolectomy followed by extensive fasciotomies was accompanied by severe reperfusion injury. Life-threatening hyperkalemia was associated with three episodes of intraoperative ventricular fibrillation and ventricular tachycardia requiring cardiac massage and defibrillation. A dextrose-insulin-bicarbonate infusion was required to correct the hyperkalemia. Rhabdomyolysis developed at 24 hours, causing marked myoglobinuria and acute renal failure, which required hemofiltration. Histology of the recovered embolus confirmed an atrial myxoma, and when the patient had fully recovered, open cardiac surgery was carried out to resect the tiny stump of residual myxoma. Rhabdomyolysis associated with a myxomatous saddle embolus has not been previously reported. This case highlights the need for pre- and perioperative measures to be taken to overcome hyperkalemia and acute renal failure when revascularizing acute, massive, prolonged ischemia of the lower body.

Acute Disease↗

The absence of cecal colonization of chicks by a mutant of Campylobacter jejuni not expressing bacterial fibronectin-binding protein.

Campylobacter jejuni is a common cause of human gastrointestinal illness throughout the world. Infections with C. jejuni and Campylobacter coli are frequently acquired by eating undercooked chicken. The ability of C. jejuni to become established in the gastrointestinal tract of chickens is believed to involve binding of the bacterium to the gastrointestinal surface. A 37-kD outer membrane protein, termed CadF, has been described that facilitates the binding of Campylobacter to fibronectin. This study was conducted to determine whether the CadF protein is required for C. jejuni to colonize the cecum of newly hatched chicks. Day-of-hatch chicks were orally challenged with C. jejuni F38011, a human clinical isolate, or challenged with a mutant in which the cadF gene was disrupted via homologous recombination with a suicide vector. This method of mutagenesis targets a predetermined DNA sequence and does not produce random mutations in unrelated genes. The parental C. jejuni F38011 readily colonized the cecum of newly hatched chicks. In contrast, the cadF mutant was not recovered from any of 60 chicks challenged, indicating that disruption of the cadF gene renders C. jejuni incapable of colonizing the cecum. CadF protein appears to be required for the colonization of newly hatched leghorn chickens.

Animals↗

Dose response and organ invasion of day-of-hatch Leghorn chicks by different isolates of Campylobacter jejuni.

Colonization of the ceca and organ invasion by different isolates of Campylobacter jejuni were investigated in day-of-hatch leghorn chicks. This model of Campylobacter colonization of the ceca demonstrates that 1) day-of-hatch birds do not naturally contain cecal Campylobacter, 2) ceca can be colonized with C. jejuni by oral gavage and not by cloacal inoculation; 3) C. jejuni can be recovered from the ceca up until at least 7 days postinoculation, 4) cecal colonization occurs when as little as 10(2) colony-forming units is orally inoculated into chicks, and 5) different C. jejuni isolates vary both in their ability to colonize the ceca and in their ability to invade the liver. These studies demonstrate that we have a working animal model for Campylobacter colonization for day-of-hatch chicks. This animal model is being used to examine intervention strategies such as vaccines by which Campylobacter can be reduced or removed from the food animal.

Animals↗

Role of Campylobacter jejuni potential virulence genes in cecal colonization.

Campylobacter jejuni, a common commensal in chickens, is one of the leading causes of bacterial gastroenteritis in humans worldwide. The aims of this investigation were twofold. First, we sought to determine whether mutations in the C. jejuni ciaB and pldA virulence-associated genes impaired the organism's ability to colonize chickens. Second, we sought to determine if inoculation of chicks with C. jejuni mutants could confer protection from subsequent challenge with the C. jejuni wild-type strain. The C. jejuni ciaB gene encodes a secreted protein necessary for the maximal invasion of C. jejuni into cultured epithelial cells, and the pldA gene encodes a protein with phospholipase activity. Also included in this study were two additional C. jejuni mutants, one harboring a mutation in cadF and the other in dnaJ, with which we have previously performed colonization studies. In contrast to results with the parental C. jejuni strain, viable organisms were not recovered from any of the chicks inoculated with the C. jejuni mutants. To determine if chicks inoculated with the C. jejuni mutants become resistant to colonization by the C. jejuni parental strain upon subsequent challenge, chicks were inoculated either intraperitoneally (i.p.) or both orally and i.p. with the C. jejuni mutants. Inoculated birds were then orally challenged with the parental strain. Inoculation with the C. jejuni mutants did not provide protection from subsequent challenge with the wild-type strain. In addition, neither the C. jejuni parental nor the mutant strains caused any apparent morbidity or mortality of the chicks. We conclude that mutations in genes cadF, dnaJ, pldA, and ciaB impair the ability of C. jejuni to colonize the cecum, that chicks tolerate massive inoculation with these mutant strains, and that such inoculations do not provide biologically significant protection against colonization by the parental strain.

Administration, Oral↗