Plasmid-mediated and temperature-regulated surface properties of Yersinia enterocolitica.

Enteropathogenic strains of Yersinia enterocolitica harbor a virulence plasmid which codes for a series of novel outer membrane proteins. The expression of these proteins on the outer membrane is temperature regulated: when cells are grown at 25 degrees C, these proteins are not exposed on the outer membrane, whereas they occur in high copy number when cells are grown at 37 degrees C. The majority of these proteins are externally exposed on the cell surface as evidenced by their susceptibility to proteolysis by exogenously added proteases. The expression of the plasmid-mediated proteins on the outer membrane does not favor adherence of the bacteria to intestinal epithelial cells in vitro. Cultures grown at 25 degrees C adhered to Henle cell monolayers, whereas those grown at 37 degrees C did so much less effectively. The presence of the proteins on the bacterial surface appears to be involved in rendering the cells resistant to the bactericidal effects of serum, i.e., 37 degrees C-grown cells were resistant to serum killing, and removal of the outer membrane proteins with pronase rendered them sensitive. Evidence is presented which strongly suggests that the plasmid-mediated proteins are synthesized and expressed on the cell surface either during or after transit of the ingested bacteria to the lamina propria. Some properties afforded to the cells by the outer membrane proteins are described.     

Pharyngeal size in snorers, nonsnorers, and patients with obstructive sleep apnea

We measured pharyngeal cross-sectional area and its change with alterations in lung volume in 10 subjects who snored and had obstructive sleep apnea, 6 subjects who snored and did not have obstructive sleep apnea, and 9 subjects who did not snore. Pharyngeal area was measured with use of an acoustic-reflection technique. We found that snorers with and without sleep apnea had a significantly smaller mean (+/- SE) pharyngeal cross-sectional area (4.1 +/- 0.2 and 3.7 +/- 0.9 cm2, respectively) at functional residual capacity than nonsnorers (5.4 +/- 0.5 cm2, P less than 0.025). When lung volume decreased from functional residual capacity to residual volume, both nonsnorers and snorers with sleep apnea had a decrease in pharyngeal area (from 5.4 +/- 0.5 to 4.5 +/- 0.4 cm2 and 4.1 +/- 0.2 to 3.4 +/- 0.2 cm2, respectively), whereas snorers without sleep apnea had no such decrease, suggesting that their pharynxes were less collapsible at low lung volumes. We conclude that snorers with and without sleep apnea have smaller pharyngeal cross-sectional areas than nonsnorers and that snorers with sleep apnea have a further decrease as lung volume falls.     

Rhinitis as an independent risk factor for adult-onset asthma

BACKGROUND: For many years, the association between asthma and rhinitis has primarily been attributed to a common allergic background. Recently, it has been suggested that asthma and rhinitis are associated in the absence of atopy. The nature of this association is not well known. OBJECTIVE: The purpose of this study, which was performed in a large, longitudinal community population, was to determine the extent to which rhinitis is an independent risk factor for adult-onset asthma. METHODS: We carried out a nested case-control study from the longitudinal cohort of the Tucson Epidemiologic Study of Obstructive Lung Diseases. One hundred seventy-three incident patients with physician-confirmed asthma were compared with 2177 subjects who reported no asthma or shortness of breath with wheezing. Potential risk factors, including the presence of rhinitis, were assessed before the onset of asthma (patients) or before the last completed survey (control subjects). RESULTS: Rhinitis was a significant risk factor for asthma (crude odds ratio, 4.13; 95% confidence interval, 2.88-5.92). After adjustment for years of follow-up, age, sex, atopic status, smoking status, and presence of chronic obstructive pulmonary disease, the magnitude of the association was reduced but still highly significant (adjusted odds ratio, 3.21; 95% confidence interval, 2.19-4.71). After stratification, rhinitis increased the risk of development of asthma by about 3 times both among atopic and nonatopic patients and by more than 5 times among patients in the highest IgE tertile. Patients with rhinitis with persistent and severe nasal symptoms and a personal history of physician-confirmed sinusitis had an additional increased risk of asthma development. CONCLUSION: We conclude that rhinitis is a significant risk factor for adult-onset asthma in both atopic and nonatopic subjects. The nature of the association between rhinitis and asthma is open to interpretation.     

Diminished lung function as a predisposing factor for wheezing respiratory illness in infants

In a prospective study of 124 infants enrolled as newborns, we assessed the relation between initial lung function and the subsequent incidence of lower respiratory tract illness during the first year of life. The risk of having a wheezing illness was 3.7 times higher (95 percent confidence interval, 0.9 to 15.5; P = 0.06) among infants whose values for total respiratory conductance (the reciprocal of the resistance to air flow of the entire respiratory system) were in the lowest third, as compared with infants with values in the upper two thirds of the range of values for the group. Boys with initial values in the lowest third for an indirect index of airway conductance had a 10-fold increase (95 percent confidence interval, 2.2 to 44.2; P = 0.001) in the risk of having a wheezing illness. A 16-fold increase (95 percent confidence interval, 1.7 to 147.1; P = 0.002) in the risk of having a wheezing illness was found among girls whose initial values for lung volume at the end of tidal expiration were in the lowest third. We conclude that diminished lung function is a predisposing factor for the development of a first wheezing illness in infants.     

Drug development strategies for asthma: in search of a new paradigm

The spiraling costs of asthma treatment seem set to continue rising, given the equivocal performance of the latest generation of specific anti-inflammatory drugs in trials in adult asthmatics. We argue that the continuation of this trend is inevitable unless there is a substantial realignment of entrenched drug development policy in the pharmaceutical industry and a parallel shift in licensing policy by regulatory authorities to encourage the development of drugs capable of halting the progression from acute to chronic asthma when the disease first manifests in childhood. The theoretical framework for such an approach, including proof-of-principle data from studies in children with early-stage disease and a range of candidate drugs, already exists. What is needed is informed debate on the risks versus potential benefits of this approach.     

Monkeypox virus detection in rodents using real-time 3'-minor groove binder TaqMan assays on the Roche LightCycler

During the summer of 2003, an outbreak of human monkeypox occurred in the Midwest region of the United States. In all, 52 rodents suspected of being infected with monkeypox virus were collected from an exotic pet dealer and from private homes. The rodents were euthanized and submitted for testing to the United States Army Medical Research Institute of Infectious Diseases by the Galesburg Animal Disease Laboratory, Illinois Department of Agriculture. The rodent tissue samples were appropriately processed and then tested by using an integrated approach involving real-time polymerase chain reaction (PCR) assays, an antigen-detection immunoassay, and virus culture. We designed and extensively tested two specific real-time PCR assays for rapidly detecting monkeypox virus DNA using the Vaccinia virus F3L and N3R genes as targets. The assays were validated against panels of orthopox viral and miscellaneous bacterial DNAs. A pan-orthopox electrochemiluminescence (ECL) assay was used to further confirm the presence of Orthopoxvirus infection of the rodents. Seven of 12 (58%) animals (seven of 52 (15%) of all animals) tested positive in both monkeypox-specific PCR assays and two additional pan-orthopox PCR assays (in at least one tissue). The ECL results showed varying degrees of agreement with PCR. One hamster and three gerbils were positive by both PCR and ECL for all tissues tested. In addition, we attempted to verify the presence of monkeypox virus by culture on multiple cell lines, by immunohistology, and by electron microscopy, with negative results. Sequencing the PCR products from the samples indicated 100% identity with monkeypox virus strain Zaire-96-I-16 (a human isolate from the Congo). These real-time PCR and ECL assays represent a significant addition to the battery of tests for the detection of various orthopoxviruses. In light of the recent monkeypox virus transmissions, early detection of the virus is crucial for both natural outbreaks and potential acts of bioterrorism.