Molecular biology of Pasteurella multocida toxin.

Pasteurella multocida toxin (PMT) is the causative agent of progressive atrophic rhinitis in swine. The 146 kDa single-chain toxin harbours discrete domains important for receptor binding, internalisation and biological activity. The molecular basis of the toxin's activity is the deamidation of a specific glutamine residue in the α-subunit of heterotrimeric G proteins. This results in an inhibition of the inherent GTPase activity leading to a constitutively active phenotype of the G protein. Due to the ability of the toxin to act on various families of heterotrimeric G proteins, a large subset of signal transduction pathways is stimulated.

Swine atrophic rhinitis caused by pasteurella multocida toxin and bordetella dermonecrotic toxin.

Atrophic rhinitis is a widespread and economically important swine disease caused by Pasteurella multocida and Bordetella bronchiseptica. The disease is characterized by atrophy of the nasal turbinate bones, which results in a shortened and deformed snout in severe cases. P. multocida toxin and B. bronchiseptica dermonecrotic toxin have been considered to independently or cooperatively disturb the osteogenesis of the turbinate bone by inhibiting osteoblastic differentiation and/or stimulating bone resorption by osteoclasts. Recently, the intracellular targets and molecular actions of both toxins have been clarified, enabling speculation on the intracellular signals leading to the inhibition of osteogenesis.

A genome-wide scan for quantitative trait loci affecting respiratory disease and immune capacity in Landrace pigs.

Respiratory disease is the most important health concern for the swine industry. Genetic improvement for disease resistance is challenging because of the difficulty in obtaining good phenotypes related with disease resistance; however, identification of genes or markers associated with disease resistance can help in the genetic improvement of pig health. The purpose of our study was to investigate whether quantitative trait loci (QTL) associated with disease resistance were segregated in a purebred population of Landrace pigs that had been selected for meat production traits and mycoplasmal pneumonia of swine (MPS) scores over five generations. We analysed 1395 pigs from the base to the fifth generation of this population. Two respiratory disease traits [MPS scores and atrophic rhinitis (AR) scores] and 11 immune-capacity traits were measured in 630-1332 animals at 7 weeks of age and when the animal's body weight reached 105 kg. Each of the pigs, except sires in the base population, was genotyped using 109 microsatellite markers, and then, QTL analysis of the full-sib family population with a multi-generational pedigree structure was performed. Variance component analysis was used to detect QTL associated with MPS or AR scores, and the logarithm of odds (LOD) score and genotypic heritability of the QTL were estimated. Five significant (LOD > 2.51) and 18 suggestive (LOD > 1.35) QTL for respiratory disease traits and immune-capacity traits were detected. The significant QTL for Log-MPS score, located on S. scrofa chromosome 2, could explain 87% of the genetic variance of this score in this analysis. This is the first report of QTL associated with respiratory disease lesions.

Primary atrophic rhinitis: a scanning electron microscopic (SEM) study.

The surface features of atrophic rhinitis are shown and it is suggested that these explain the majority of symptoms. It seems clear that any lesion preventing the formation or maturation of large numbers of motile cilia, or the production of mucus capable of forming confluent sheets suitable for continuous propulsion, may cause atrophic rhinitis. In both familial and idiopathic forms of the disease, both abnormalities are present. It would be most interesting to know the ultrastructure of the cilia in transverse section of this condition. Transverse electron microscopic studies in Retinitis Pigmentosa, Usher's syndrome and Kartagener's syndrome now becoming known as the low cilia motility diseases show clearly the primary lesions in the micro-tubules and dynein arms of the cilia. A similar transmission electron microscopic study in atrophic rhinitis may show the fundamental cilial lesions. Surgical closure of the nasal passages has much to offer the patient with severe symptoms as the clinical features of the disease improve with the increasing normal micro-anatomical features demonstrated in this paper as a result of closure. This improvement in structure is not in all cases sufficient to fulfil the above criteria so a complete cure is improbable in the majority of cases.

[Genetic nature of atrophic rhinitis in swine. II. Cytogenetic research]. / Geneticheskaia priroda atroficheskogo rinita. Soobshchenie II. Tsitogeneticheskoe issledovanie.

This work is concerned with the problem of the nature of the atrophic rhinitis in swine. Our study demonstrates that the filter-passers when injecting intranasal provoke catarrhal rhinitis in sucking-pigs and rabbits and the disease lasts 10-12 days. Guinea-pigs and white mice show no disease symptoms after injection. After four passages of filter-passers through sucking-pigs, the pathogenic properties do not restore. The sucking-pigs and laboratory animals show no changes in organs and in nasal cavity. The findings of cytogenetic and allergic investigations indicate genetic aspects of this disease. To eliminate atrophic rhinitis, it is necessary to reveal heterozygotes, carry out experimental matings and analysis of hybrids. To date, a recessive gene is considered to mediate the disease. To obtain healthy offspring, animals heterozygous for this gene should be bred.

[Veterinary genetics]. / O veterinarnoi genetike

At the age of scientific and technical progress and of industrialization of animal husbandry neither theoretical nor applied science can dispense with the data of the veterinary genetics. Unfortunately this branch of science does not receive the attention it deserves. The following three problems have to be solved by the veterinary genetics: (1) the investigation of the relationship between the heredity and the pathology of animals; the examination of the mechanism of pathology at the molecular and organism genetic levels; (2) the elaboration of the methods of genetic diagnostics; (3) the search for scientifically-substantiated directions in breeding of animal breeds highly resistant to diseases. The main attention will be paid to the investigation of the mechanisms ensuring the natural resistance of animals to certain definite diseases. The establishment and development of veterinary genetics will exert a favourable influence on the progress of biological sciences. Its data will be indispensable both for the theory and the practice of agriculture.

[Genetic nature of atrophic rhinitis in swine. I. The results of a test cross and bacteriological study in atrophic rhinitis in swine]. / Geneticheskaia priroda atroficheskogo rinita u svinei. Soobshchenie I. Rezul'taty analiziruiushchego skreshchivaniia i bakteriologicheskogo issledovaniia pri atroficheskom rinite u svinei.

It is well established that the swine atrophic rhinitis (AR) is controlled by the only gene with two alleles, R and r, the former being a dominant. Our study was designed to determine the role of these factors in appearance of AR of swine among the offspring. Normal and diseased pairs of animals were mated. The heterozygotic (Rr) phenotypically normal but potentially ill hogs and sows were revealed at the farm where AR was spread. The phenotypically normal hogs and sows (RR, Rr) were mated with diseased (rr) or potentially diseased ones, and phenotypically normal heterozygotic (Rr) hogs and sows (control). The diseased sucking-pigs revealed in the litter were removed. It has been established that the sucking-pigs were normal when mating normal homozygotic animals. These sucking-pigs were used to replace the live-stock of sows. When mating normal homozygotic animals with recessive ones, the sucking-pigs were also normal, the normal alleles being dominant. In matings of heterozygotic animals 27.3% of the litter were wry-snouted. However, even healthy heterozygotic animals should not be used for replacing the live-stock, because they have both the normal and recessive alleles. When recessive animals were mated, all sucking-pigs proved to have the symptoms of AR. Such sucking-pigs, together with their parents were necessarily removed.

Dominant inheritance in a family with primary atrophic rhinitis.

Primary atrophic rhinitis is an uncommon condition which presents with crusts in the nose. The nasal mucosa is dry and atrophied and the nasal cavities are abnormally wide. We report a large London Irish family with an affected father with fifteen children. Eight of these have primary atrophic rhinitis. Symptoms appear around puberty, and there was one case in the third generation with an affected mother. The nasal appearances of the affected members varied considerably and many hid their disease well. The family fits well with dominant inheritance. A familial aetiology for primary atrophic rhinitis is a more attractive theory than those previously postulated.

Cloning of the toxin gene from Pasteurella multocida and its role in atrophic rhinitis.

The gene for the osteolytic toxin of Pasteurella multocida has been cloned into a plasmid vector and expressed off its own promoter in Escherichia coli. Particular restriction endonucleases failed to cut the gene and regions flanking it, suggesting an A + T base ratio significantly greater than the remaining genome of P. multocida. Cloned toxin was indistinguishable from the native toxin with respect to molecular mass, antigenicity and toxicity in different tests. A single intraperitoneal injection of toxin purified from the recombinant E. coli reproduced in gnotobiotic pigs the pathological changes characteristic of atrophic rhinitis. The recombinant E. coli produced at least 10 times as much toxin as P. multocida.

Clinical, genetic and immunologic analysis of a family affected by ozena.

Primary atrophic rhinitis is a chronic inflammation of the nasal mucosa characterized by atrophy of the mucous and bony tissue of the turbinates and by a thick, dense secretion, which quickly forms a characteristically fetid-smelling, greenish crust. We report the results of the clinical, genetic and immunologic investigations performed on eight subjects (three with ozena and five asymptomatic), members of the same familial group. The presence of the disease in the family fits well with dominant inheritance. All the culture specimens from the patients affected by ozena were positive for Klebsiella ozaenae, and one of them was also positive for Pseudomonas aeruginosa. All the three patients with ozena and two of the five apparently unaffected family members were positive for antinuclear antibodies. Immunoblotting showed a reactivity to a 50-kD protein, which was not identified by the common, recognized nuclear autoantigens. This was present in one of the three patients and three of the five other family members. Positivity for IgG-class anticardiolipins was correlated with disease manifestation in that it was found in two of the three patients and only in one of the five asymptomatic family members. The hypothesis of a genetic factor that could drive the chronicity of the inflammatory pattern of a pre-existing infectious nasal disease is suggested.

[A preliminary study on etiology of atrophic rhinitis in Zunyi].

200 cases (households with atrophic rhinitis (AR) diagnosed from outpatients and mobile medical team as the AR group were studied. Another 200 cases (households) served as the control group, who were residents of countryside and members of a factory in Zunyi, and they have lived in Zunyi for more than 20 years. The subjects between the two groups were similar in age and sex. Each of these two groups was further divided into two groups, the opentype stove group (100 cases) and the closetype stove group (100 cases). The heritability (h2, 59.4 +/- 0.032%) was estimated by using the method of Falconer liability threshold. The concentration of SO2 in living environment was monitored with Parafuchsin colorimetry. The daily average SO2 concentrations have been drawn for comparison. The result showed that the SO2 concentration of living environment in AR group was significantly higher than that in control group (P < 0.01). We believe that the contraction and development of AR were determined by the combination of inheritance with environment. This fact suggests that AR may be transmitted in a multigenic and multifacterial modes.

[Ozena and allergic rhinitis in ichthyosis vulgaris]. / Ozaena und allergische Rhinitis bei Ichthyosis vulgaris.

The clinical course of an ozaena in a patient with an autosomal dominant ichthyosis vulgaris was complicated by the skin disease related atopic disposition with allergic rhinitis. Electron microscopic studies of the pathologically keratinized mucosa of the nasopharynx revealed a similar defect of the mucosal keratohyalin caused by the absence of the protein filaggrin.