A comparative ultrastructural and molecular biological study on Chlamydia psittaci infection in alpha-1 antitrypsin deficiency and non-alpha-1 antitrypsin deficiency emphysema versus lung tissue of patients with hamartochondroma

BACKGROUND: Chlamydiales are familiar causes of acute and chronic infections in humans and animals. Human pulmonary emphysema is a component of chronic obstructive pulmonary disease (COPD) and a condition in which chronic inflammation manifested as bronchiolitis and intra-alveolar accumulation of macrophages is common. It is generally presumed to be of infectious origin. Previous investigations based on serology and immunohistochemistry indicated Chlamydophila pneumoniae infection in cases of COPD. Furthermore, immunofluorescence with genus-specific antibodies and electron microscopy suggested involvement of chlamydial infection in most cases of pulmonary emphysema, but these findings could not be verified by PCR. Therefore, we examined the possibility of other chlamydial species being present in these patients. METHODS: Tissue samples from patients having undergone lung volume reduction surgery for advanced alpha-1 antitrypsin deficiency (AATD, n = 6) or non-alpha-1 antitrypsin deficiency emphysema (n = 34) or wedge resection for hamartochondroma (n = 14) were examined by transmission electron microscopy and PCR. RESULTS: In all cases of AATD and 79.4% of non-AATD, persistent chlamydial infection was detected by ultrastructural examination. Intra-alveolar accumulation of macrophages and acute as well as chronic bronchiolitis were seen in all positive cases. The presence of Chlamydia psittaci was demonstrated by PCR in lung tissue of 66.7% AATD vs. 29.0% non-AATD emphysema patients. Partial DNA sequencing of four positive samples confirmed the identity of the agent as Chlamydophila psittaci. In contrast, Chlamydophila pneumoniae was detected only in one AATD patient. Lung tissue of the control group of non-smokers with hamartochondroma was completely negative for chlamydial bodies by TEM or chlamydial DNA by PCR. CONCLUSIONS: These data indicate a role of Chlamydophila psittaci in pulmonary emphysema by linking this chronic inflammatory process to a chronic infectious condition. This raises interesting questions on pathogenesis and source of infection

Speaking and writing English

The study of spoken English is exciting, challenging, and controversial: exciting, because new and unexpected constructions keep turning up; challenging, because some syntactic constructions of spoken language resist analysis; controversial, because not all researchers recognize the study of spoken language as legitimate, far less its results. The very title of this chapter is controversial, since spoken language tout court does not differ from written language and analysts recognize genres or dimensions applying to both speech and writing (see Section 27.5). Nonetheless, spontaneous spoken language (Miller Weinert 1998) or conversation (Greenbaum and Nelson 1995a) is very different from other genres and that is the focus of this chapter

Randomized, double-blind, placebo-controlled phase 3 trial of the safety and tolerability of IC51, an inactivated Japanese encephalitis vaccine

Background. Japanese encephalitis (JE) is the most important mosquito‐borne viral encephalitis and has a high case fatality rate. It is caused by Japanese encephalitis virus. Improved vaccines are urgently needed for residents in countries of endemicity, travelers, and the military. The aim of the present trial was to evaluate the safety and tolerability of IC51, Intercell's Vero cell–derived, purified, inactivated JE vaccine.\ud \ud Methods. This was a randomized (3:1), double‐blind, placebo‐controlled, multicenter phase 3 trial. Healthy subjects were randomized to receive 2 doses of IC51 (n=2012) or placebo (n=663) at a 4‐week interval. Adverse events following immunization (AEFI) were documented over a period of 2 months.\ud \ud Results.The rate of severe AEFI was similar in the IC51 group (0.5%) and the placebo group (0.9%). The rate of medically attended AEFI and all AEFI was also similar in the IC51 group and the placebo group. The same applied for all adverse events, including local and systemic tolerability. Importantly, there were no signs of acute allergic reactions.\ud \ud Conclusion. The Intercell JE vaccine IC51 had a safety profile similar to that of placebo. These data, together with the immunogenicity data from a recent phase 3 trial, form the basis of application for licensure of this vaccine.\ud \ud Trial registration. ClinicalTrials.gov identifier: NCT00605058