Evaluation of the role of the Yersinia pestis plasminogen activator and other plasmid-encoded factors in temperature-dependent blockage of the flea

Yersinia pestis, the plague bacillus, has a plasminogen activator (pla) gene on the 9.5-kb plasmid pPla that is hypothesized to play a role in producing the foregut blockage in the flea vector that precedes transmission. In this study, however, Y. pestis that lacked pPla, the 70-kb virulence plasmid, or both plasmids, proved able to block Xenopsylla cheopis fleas normally. Blockage rates decreased with increasing environmental temperature for fleas infected with either wild type or pPla- Y. pestis. Thus, procoagulant ability of the Y. pestis pla gene product does not mediate blockage, nor does its ability to induce fibrinolysis at>28 degreesC account for failure to block at elevated temperatures. A Y. pestis strain that lacked all or part of the third plasmid of 110 kb, however, failed to colonize the flea midgut normally, indicating that one or more genes on the large plasmid may be required for vectorborne transmission.     

A study of the vascular and acid-secretory responses of the rat gastric mucosa to histamine

1. The effects of histamine on gastric mucosal blood flow in the presence and absence of gastric acid secretion were studied in the rat. 2. Histamine, in doses greater than those required to stimulate maximal acid secretion, caused a small increase in mucosal blood flow per unit acid output. 3. When acid secretion was inhibited by methyl analogues of prostaglandin E2, histamine reduced arterial blood pressure and gave a dose dependent rise in mucosal blood flow. 4. When acid secretion was inhibited by the histamine H2-receptor antagonists, burimamide and metiamide, histamine still increased mucosal blood flow. 5. The use of H1-receptor antagonists to inhibit the histamine-induced hyperaemia was made difficult by their vasodilator actions. 6. The selective histamine H2-receptor agonist, 4-methyl histamine, had no effect on arterial blood pressure in doses which stimulated acid secretion. The increase in mucosal blood flow which accompanied the stimulation of acid secretion was inhibited by the anti-secretory prostaglandins and H2-receptor antagonists. 7. The selective histamine H1-receptor agonist, 2-pyridyl ethylamine, had no effect on acid output but increased resting mucosal blood flow. 8. These results suggest that histamine H2-receptors, primarily concerned with acid secretion, and H1-receptors concerned with vasodilatation are both present in the rat gastric mucosa.     

Vaccine genotype and route of administration affect pseudorabies field virus latency load after challenge

The influence of vaccine genotype and route of administration on the efficacy of pseudorabies virus (PRV) vaccines against virulent PRV challenge was evaluated in a controlled experiment using five genotypically distinct modified live vaccines (MLVs) for PRV. Several of these MLVs share deletions in specific genes, however, each has its deletion in a different locus within that gene. Pigs were vaccinated with each vaccine, either via the intramuscular or intranasal route, and subsequently challenged with a highly virulent PRV field strain. During a 2-week period following challenge with virulent PRV, each of the vaccine strains used in this study was evaluated for its effectiveness in the reduction of clinical signs, prevention of growth retardation and virulent virus shedding. One month after challenge, tissues were collected and analyzed for virulent PRV latency load by a recently developed method for the electrochemiluminescent quantitation of latent herpesvirus DNA in animal tissues after PCR amplification. It was determined that all vaccination protocols provided protection against clinical signs resulting from field virus challenge and reduced both field virus shedding and latency load after field virus challenge. Our results indicated that vaccine efficacy was significantly influenced by the modified live vaccine strain and route of administration. Compared to unvaccinated pigs, vaccination reduced field virus latency load in trigeminal ganglia, but significant differences were found between vaccines and routes of administration. We conclude that vaccine genotype plays a role in the effectiveness of PRV MLVs.     

Morphology of peripheral airways in current smokers and ex-smokers

To investigate the effect of smoking status on pulmonary function and pathologic changes in the peripheral airways, we studied 97 patients who underwent thoracotomy for coin lesions. The patients were divided into 4 groups: nonsmokers (n = 9), current smokers (n = 51), and those who had ceased smoking for less than (n = 18) or more than (n = 19) 2 yr prior to surgery. We found that current smokers had evidence of air-flow obstruction with abnormal lung volumes when compared with nonsmokers. Ex-smokers had lung volumes similar to those of nonsmokers, but showed evidence of obstruction, with the FEV1/FVC between the values found for nonsmokers and current smokers. Examination of the small airways showed that the membranous bronchioles of current smokers and ex-smokers displayed only increased goblet cell metaplasia when compared with those in nonsmokers; the respiratory bronchioles of current and ex-smokers showed increases in intraluminal and airway wall inflammatory cells, wall fibrosis, and pigment deposition. We conclude that patients who currently smoke cigarettes have reduced lung function that is associated with abnormalities of airway structure. Although those who have stopped smoking have function that is closer to the nonsmoking group, there is no apparent difference in structural change between current and ex-smokers.