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Biomedical subjects

John W Wilson

Publications and source records attributed to John W Wilson.

At least 19 recordsLinked to original sources
PubMed2007

Efficacy of a heated passover humidifier during noninvasive ventilation: a bench study.

BACKGROUND: Noninvasive positive-pressure ventilation (NPPV) delivers air at a high flow, which is associated with airway mucosal drying and impaired airway functioning. OBJECTIVES: To examine the effects of mechanical ventilation parameters on relative humidity and absolute humidity during NPPV, and to evaluate the effect of a heated passover humidifier on relative humidity, absolute humidity, and ventilator performance during NPPV. METHODS: We performed a bench study to assess the effects of inspiratory positive airway pressure (IPAP) of 10 cm H(2)O, 15 cm H(2)O, and 20 cm H(2)O, respiratory rates of 12 breaths/min and 24 breaths/min, and inspiratory-expiratory ratios of 1:2 and 1:3 on relative and absolute humidity. The measurements were obtained on room air and with a heated humidifier at medium and maximum heater settings. RESULTS: Without humidification, the relative humidity in the NPPV circuit (range 16.3-26.5%) was substantially lower than the ambient relative humidity (27.6-31.5%) at all ventilatory settings. Increasing the IPAP decreased the relative humidity (Spearman's rho = 0.67, p < 0.001). Changing the respiratory rate or inspiratory-expiratory ratio had no significant effect. Both relative and absolute humidity increased with humidification, and the air was fully saturated at the maximum heater setting. Delivered IPAP was reduced by 0.5-1 cm H(2)O during humidification. CONCLUSIONS: NPPV delivers air with a low relative humidity, especially with high inspiratory pressure. Addition of a heated humidifier increases the relative and absolute humidity to levels acceptable for nonintubated patients, with minimal effect on delivered pressure. Consideration should be given to heated humidification during NPPV, especially when airway drying and secretion retention are of concern.

Benchmarking↗
PubMed2006

A temporal forecast of radiation environments for future space exploration missions.

The understanding of future space radiation environments is an important goal for space mission operations, design, and risk assessment. We have developed a solar cycle statistical model in which sunspot number is coupled to space-related quantities, such as the galactic cosmic radiation (GCR) deceleration potential (phi) and the mean occurrence frequency of solar particle events (SPEs). Future GCR fluxes were derived from a predictive model, in which the temporal dependence represented by phi was derived from GCR flux and ground-based Climax neutron monitor rate measurements over the last four decades. These results showed that the point dose equivalent inside a typical spacecraft in interplanetary space was influenced by solar modulation by up to a factor of three. It also has been shown that a strong relationship exists between large SPE occurrences and phi. For future space exploration missions, cumulative probabilities of SPEs at various integral fluence levels during short-period missions were defined using a database of proton fluences of past SPEs. Analytic energy spectra of SPEs at different ranks of the integral fluences for energies greater than 30 MeV were constructed over broad energy ranges extending out to GeV for the analysis of representative exposure levels at those fluences. Results will guide the design of protection systems for astronauts during future space exploration missions.

Computer Simulation↗
PubMed2006

Work disability in adults with cystic fibrosis and its relationship to quality of life.

UNLABELLED: With increasing numbers of cystic fibrosis (CF) patients surviving to adulthood, issues related to vocation inevitably arise and warrant specific attention. We examined the percentage of participants with CF currently working and explored risk factors for work disability among adults with CF. METHOD: We recruited 50 consecutive patients from an adult cystic fibrosis service. Demographic, employment history, illness severity indicators and CF-attributed work disability factors were evaluated. Demographic risk factors for work disability using the illness severity measures of FEV(1), S-K score, CRDQ, and recent hospitalisation as independent variables were determined. RESULTS: Factorial analysis of a disability index (DI) indicated no dependency on FEV(1) or S-K score, but dependency on quality of life indices (p<0.05), age (p<0.05) and hospital admission rate (p<0.05). Hours worked per week were dependent on quality of life (p<0.01) (mastery of disease domain), fewer hospital admissions (p<0.01) and age (p<0.05). Sixty-eight percent of the sample reported that CF resulted in significant impediments to employment. However, few had sought vocational guidance (6%). CONCLUSION: Determinants of workforce participation shows that hours worked and perceived disability are more dependent on mastery of disease, age, and time in hospital, than on clinical severity scores. Health professionals may assist productivity through career counselling or tailored programs.

Adult↗
PubMed2006

Linezolid and serotonergic drug interactions: a retrospective survey.

BACKGROUND: Linezolid is a reversible, nonselective monoamine oxidase inhibitor. There are currently 11 published case reports of serotonin syndrome being associated with linezolid and selective serotonin reuptake inhibitors (SSRIs). Controversy exists regarding whether linezolid and SSRIs can be given concomitantly. The purpose of this study was to report the incidence of serotonin syndrome in patients receiving linezolid and SSRIs. METHODS: This study was a retrospective chart review of inpatients at the Mayo Clinic (Rochester, MN) with concomitant orders or therapy within 14 days for linezolid and an SSRI from 2000 to 2004. The Sternbach criteria and Boyer criteria for diagnosis of serotonin syndrome were used to identify clinical features of serotonin syndrome. RESULTS: Seventy-two patients received linezolid and an SSRI or venlafaxine within 14 days of each other. Fifty-two patients (72%) received concomitant therapy with linezolid and an SSRI or venlafaxine, and 20 patients (28%) did not receive concomitant therapy but received linezolid and an SSRI within a 14-day period. Overall, only 2 patients (3%) had a high probability of serotonin syndrome. In both patients with high probability, symptoms reversed rapidly on discontinuation of serotonergic therapy. The Boyer criteria were much more specific than the Sternbach criteria for identification of serotonin syndrome. CONCLUSIONS: On the basis of our experience, we suggest that, if the clinical situation warrants use of linezolid in a patient receiving an SSRI, linezolid may be used concomitantly with SSRIs, without a 14-day washout period and with careful monitoring for signs and symptoms of serotonin syndrome. Serotonergic agents should be promptly discontinued if serotonin syndrome is suspected.

Acetamides↗
PubMed2006

Airway remodelling in asthma: current understanding and implications for future therapies.

Airway remodelling refers to the structural changes that occur in the airway wall in asthma. These include epithelial hyperplasia and metaplasia, subepithelial fibrosis, muscle cell hyperplasia and angiogenesis. These structural changes result in thickening of the airway wall, airway hyperresponsiveness (AHR), and a progressive irreversible loss of lung function. The precise sequence of events that take place during the remodelling process and the mechanisms regulating these changes remain poorly understood. It is thought that airway remodelling is initiated and promoted by repeated episodes of allergic inflammation that damage the surface epithelium of the airway. However, other mechanisms are also likely to contribute to this process. Moreover, the interrelationship between airway remodelling, inflammation and AHR has not been clearly defined. Currently, there are no effective treatments that halt or reverse the changes of airway remodelling and its effects on lung function. Glucocorticoids have been unable to eliminate the progression of remodelling changes and there is limited evidence of a beneficial effect from other available therapies. The search for novel therapies that can directly target individual components of the remodelling process should be made a priority. In this review, we describe the current understanding of the airway remodelling process and the mechanisms regulating its development. The impact of currently available asthma therapies on airway remodelling is also discussed.

Adrenergic beta-Agonists↗
PubMed2006

Monocyte fructose 1,6-bisphosphatase and cytidine deaminase enzyme activities: potential pharmacodynamic measures of calcitriol effects in cancer patients.

PURPOSE: To determine, in peripheral blood monocytes (PBM), whether the enzymatic activities of fructose 1,6-bisphosphatase (FBPase), cytidine deaminase (CDDase) and 24-hydroxylase (CYP24), enzymes regulated by calcitriol are useful pharmacodynamic (PD) measures of calcitriol effects in cancer patients. METHODS: Cancer patients enrolled in a phase I clinical trial of calcitriol and carboplatin were studied. Baseline and calcitriol-induced changes in FBPase, CDDase and CYP24 activities were measured in PBM collected before, 6, 24, and 48 h after administration of calcitriol, prior to carboplatin, in doses ranging from 4 to 11 mug daily for 3 consecutive days (QDx3). Normal FBPase, CYP24 and CDDase activities were measured in PBM from untreated healthy volunteers. RESULTS: Baseline activities in PBM from cancer patients and healthy volunteers were (median and range): 1.0 (0.0-43.5) and 4.4 (3.1- 8.2) nmol/min/mg protein for FBPase (P = 0.002); 2.5 (0.9-9.3) and 0.8 (0.4-2.0) fmol/h/10(6) cells for CYP24 (P = 0.016), and 5.6 (2.5-22.3) and 6.6 (1.1-47.4) nmol/min/mg protein for CDDase (P > 0.05), respectively. All calcitriol doses achieved peak serum calcitriol levels > x3 the physiological levels, increased cancer patient PBM FBPase activity to normal levels and decreased CDDase activity to undetectable levels within 48 h, with no significant change in CYP24 activity. These enzyme activity changes were not associated with hypercalcemia. CONCLUSIONS: Calcitriol treatment-induced increase in FBPase and decrease in CDDase activities in cancer patient PBM are potential early and sensitive non-hypercalcemia PD measures of calcitriol effects.

Adolescent↗
PubMed2006

Identification of functional single nucleotide polymorphism haplotypes in the cytidine deaminase promoter.

Cytidine deaminase (CDA) hydrolytically deaminates and irreversibly deactivates the chemotherapeutic agent cytosine arabinoside (Ara-C), a deoxycytidine analog used for treatment of acute leukemias and lymphomas. To determine if single nucleotide polymorphisms (SNPs) in the promoter region of CDA affected gene expression, we sequenced approximately 1.6 Kb upstream of the CDA translation initiation site and containing the proximal promoter of CDA. We identified 6 SNPs; -92A>G, -205C>G, -451C>T, -897C>A, -1075A>G and -1181G>A. Based on predicted changes in transcription factor binding sites, three SNPs (-92A>G, -451C>T and -897C>A) were chosen for further investigation. The five haplotypes segregating in the population were cloned into a luciferase expression plasmid, transfected into Cos-1 cells and reporter activity measured at 24 and 48 h. Four haplotypes showed an average expression which was 2.5-fold higher at 24 h (P<0.0001) and 3.3-fold higher at 48 h (P<0.0001) than the lowest expressing haplotype. When reanalyzed as single SNP genotypes, the differences in expression were significant, except for -897 C/A, at 24 h, but the magnitude of difference was reduced, suggesting that no single SNP completely accounts for the expression differences observed at the haplotype level. As predicted from the in vitro analysis, individuals homozygous for common haplotype (ACC/ACC) showed higher levels of CDA enzymatic activity as individuals heterozygous for the wild type and low expressing haplotype (ACC/ATC). As CDA promoter region haplotypes may influence Ara-C chemosensitivity, shown here in in vitro and in vivo studies, the clinical relevance of these findings should be examined.

Animals↗
PubMed2006

Skin and soft tissue infections due to rapidly growing mycobacteria: comparison of clinical features, treatment, and susceptibility.

OBJECTIVE: To compare the demographics, clinical features, susceptibility patterns, and treatment for skin and soft tissue infections due to Mycobacterium fortuitum and Mycobacterium chelonae or Mycobacterium abscessus. DESIGN: Retrospective medical record review. SETTING: Mayo Clinic, Rochester, Minn. PATIENTS: All patients seen at our institution with a positive culture for M chelonae, M abscessus, or M fortuitum from skin or soft tissue sources between January 1, 1987, and October 31, 2004. MAIN OUTCOME MEASURES: Patient demographics, clinical characteristics, therapeutic data, microbiological data, and outcomes. RESULTS: The medical records of 63 patients with skin or soft tissue infections due to rapidly growing mycobacteria were reviewed. Patients with M chelonae or M abscessus were older (61.5 vs 45.9 years, P<.001) and more likely to be taking immunosuppressive medications (60% vs 17%, P = .002) than patients with M fortuitum. Mycobacterium fortuitum tended to manifest as a single lesion (89% vs 38%, P<.001), while most M chelonae or M abscessus manifested as multiple lesions (62% vs 11%, P<.001). More patients with M fortuitum had a prior invasive surgical procedure at the infected site (56% vs 27%, P = .04). Patients with multiple lesions were more likely to be taking immunosuppressive medications than those with single lesions (67% vs 30%, P = .006). Seven patients failed treatment, several of whom were immunocompromised and had multiple comorbidities. CONCLUSIONS: Skin and soft tissue infections due to rapidly growing mycobacteria are associated with systemic comorbidities, including the use of immunosuppressive medications. There are significant differences in the demographic and clinical features of patients who acquire specific organisms, including association with immunosuppression and surgical procedures.

Administration, Cutaneous↗
PubMed2006

Vascular endothelial growth factor induction by rhinovirus infection.

Vascular participation manifested by a runny nose (rhinorrhea) is a prominent feature of the acute consequences of rhinovirus infection. Vascular endothelial growth factor (VEGF) is an angiogenic factor that also induces potent increases in vascular permeability; it is a candidate mediator of rhinorrhea in response to rhinovirus infection as well as contributing to enhanced vascular leakage in rhinovirus-linked asthma exacerbations. It has been shown that rhinovirus induces significant increases in both VEGF protein and mRNA in primary airway fibroblasts [Ghildyal et al. (2005): J Med Virol 75:608-615]. The current studies assessed VEGF responses to rhinovirus in primary culture airway epithelium, in epithelial and fibroblast cell lines and in rhinovirus-infected nasal secretions. Epithelial and fibroblast cells were infected with rhinovirus serotype 16 and VEGF protein and isoforms assessed by ELISA and RT-PCR, respectively. VEGF protein was released by both epithelial and fibroblast cell lines and primary airway epithelial cells in culture but was not increased following rhinovirus infection. PCR products coding for four or five of the six known VEGF isoforms were produced (121, 145, 165 and 183, and/or 189 amino acids) in cell lines and primary culture cells, but no specific isoform was linked to rhinovirus infection. Nasal VEGF was also measured in a cohort of asthmatics with verified rhinovirus and respiratory syncytial virus (RSV) infection. VEGF was not raised following rhinovirus infection alone, but was increased significantly if concomitant RSV infection was present. The data suggest that fibroblasts rather than the epithelium may play a key role in VEGF mediated vascular responses after rhinovirus infection. This may aid recruitment of inflammatory cells and contribute to airway inflammation and bronchial obstruction.

Asthma↗
PubMed2006

The importance of the airway microvasculature in asthma.

PURPOSE OF REVIEW: The microvasculature in asthma has been known to contribute to airway-wall thickening and oedema from early post-mortem series. Current concepts of airway inflammation in asthma highlight the importance of the role of the Th2 lymphocyte in the atopic response to aeroallergens, the importance of mast-cell mediators in airway remodelling, potential actions of the vascular response in determining airway thickness and mechanisms of angiogenesis involving endogenous as well as homing progenitor cells with angioblastic potential. RECENT FINDINGS: The development of animal models of asthmatic airway inflammation and remodelling have given new insight into mechanisms of angiogenesis in asthma. The central role of vascular endothelial growth factor in angiogenesis, vessel leakage and vascular homeostasis is now recognized. A more recent finding is the influence of this factor in enhancing the Th2 response in airway inflammation. The ability of bone marrow-derived angioblasts to migrate to sites of inflammation and contribute to angiogenesis indicates a pivotal role of stem cells in this process. SUMMARY: These findings now provide logical links between the inflammatory response, stem-cell mobilization, angiogenesis and airflow obstruction in the remodelled airway of asthma. Future studies examining airway-wall thickness will be able to account for the contribution of the vasculature and airway-wall oedema. Therapies aimed at vascular mechanisms may be useful adjuncts to current treatments and the recognition of stem cells as key players in airway remodelling may provide strategies to reduce fixed airflow obstruction in severe disease.

Animals↗
PubMed2006

Functional single nucleotide polymorphism haplotypes in the human equilibrative nucleoside transporter 1.

The human equilibrative nucleoside transporter 1 gene (hENT1) is the primary nucleoside transporter for cytosine arabinoside (AraC), a deoxycytidine analog used for treatment of acute leukemias and lymphomas. We screened approximately 1.6 kb upstream of the transcription initiation site of hENT1 for single nucleotide polymorphisms (SNPs) that affect gene expression. We identified one SNP at position -706G>C with a frequency of 21% in whites and 5% in African-Americans. In African-Americans, we observed two SNPs at positions -1345C>G and -1050G>A with allele frequencies of 8% and 19%, respectively. TRANSFAC analysis suggested that -1345C>G and -706G>C may alter transcription factor binding sites. Four naturally occurring haplotypes (CGG, CAG, CGC and GAG) were cloned into a luciferase expression plasmid, transfected into Cos-1 cells, and reporter activity measured at 24 and 48 h. Three haplotypes, CAG, CGC and GAG, respectively, showed average expression that was approximately two-fold (P<0.05), 1.4-fold (P<0.05) and 1.1-fold (P>0.05) higher than lowest expression haplotype CGG at 48 h. When reanalysed as single SNPs, the differences in expression were significant for -1345C>G and -1050G>A genotypes, and not for -706G>C. However, the magnitude of difference was reduced, suggesting that no single SNP completely accounts for the expression differences observed at the haplotype level. By real-time quantitative reverse transcriptase-polymerase chain reaction assay, individuals with CGG/CGC haplotypes showed 1.37-fold higher median expression of hENT1 transcript than those with common CGG/CGG haplotypes. Although not statistically significant (P=0.12), this difference is in the direction predicted by the in vitro data. hENT1 promoter region haplotypes may influence gene expression and alter AraC chemosensitivity.

Black or African American↗
PubMed2006

Implementing practice guidelines: a workshop on guidelines dissemination and implementation with a focus on asthma and COPD.

The present supplement summarizes the proceedings of the symposium "Implementing practice guidelines: A workshop on guidelines dissemination and implementation with a focus on asthma and COPD", which took place in Quebec City, Quebec, from April 14 to 16, 2005. This international symposium was a joint initiative of the Laval University Office of Continuing Medical Education (Bureau de la Formation Médicale Continue), the Canadian Thoracic Society and the Canadian Network for Asthma Care, and was supported by many other organizations and by industrial partners. The objectives of this meeting were to examine the optimal implementation of practice guidelines, review current initiatives for the implementation of asthma and chronic obstructive pulmonary disease (COPD) guidelines in Canada and in the rest of the world, and develop an optimal strategy for future guideline implementation. An impressive group of scientists, physicians and other health care providers, as well as policy makers and representatives of patients' associations, the pharmaceutical industry, research and health networks, and communications specialists, conveyed their perspectives on how to achieve these goals. This important event provided a unique opportunity for all participants to discuss key issues in improving the care of patients with asthma and COPD. These two diseases are responsible for an enormous human and socioeconomic burden around the world. Many reports have indicated that current evidence-based guidelines are underused by physicians and others, and that there are many barriers to an effective translation of recommendations into day-to-day care. There is therefore a need to develop more effective ways to communicate key information to both caregivers and patients, and to promote appropriate health behaviours. This symposium contributed to the initiation of what could become the "Canadian Asthma and COPD Campaign", aimed at improving care and, hence, the quality of life of those suffering from these diseases. It is hoped that this event will be followed by other meetings that focus on how to improve the transfer of key recommendations from evidence-based guidelines into current care, and how to stimulate research to accomplish this.

Asthma↗
PubMed2006

Identifying regions of compromised hemodynamics in symptomatic carotid occlusion by cerebrovascular reactivity and oxygen extraction fraction.

OBJECTIVES: Oxygen extraction fraction (OEF) and cerebrovascular reserve (CVR) are both proven predictors of stroke risk in symptomatic patients with carotid occlusion. Accordingly, hemispheric comparisons of CVR and OEF are significantly correlated. However, there was also substantial disagreement: hemispheres identified as compromised by CVR were normal by OEF. Our aim was to determine whether regional comparisons could resolve the CVR-OEF discordance. We also studied the relationship between white matter (WM) infarction and hemodynamic compromise. METHODS: Quantitative CVR and OEF were measured in 12 symptomatic patients with internal carotid artery occlusion. CVR and OEF comparisons were made in the anterior watershed (AWS), middle cerebral artery (MCA) and WM territories using various thresholds for hemodynamic compromise. Associations with WM infarction were also recorded. RESULTS: Comparison of CVR and OEF for the AWS and MCA showed high sensitivity (100%) with specificities of 83 and 40%, respectively. There was also agreement (k=Cohen's Kappa) for the AWS (k=0.83) and MCA (k=0.39) territories. CVR-OEF discordance was reduced with regional analysis. Hemodynamic compromise was more often found in patients with WM infarction. DISCUSSION: Regional comparison of CVR and OEF reduced the discordance compared with hemispheric analysis, especially for the AWS territory. Despite the persistence of some regions with compromised CVR and normal OEF, CVR is able to identify all regions with elevated OEF making it a useful screening technology. Future studies are needed to understand whether those remaining regions with compromised CVR are also at increased stroke risk despite normal OEF.

Aged↗
PubMed2006

Diverticular disease in patients with colon cancer: subgroup analysis of national surgical adjuvant breast and bowel project protocol C-06.

BACKGROUND: Similar epidemiologic characteristics suggest a common etiology for colon cancer (CC) and diverticular disease of the colon (DD). The relationship between the 2 diseases is still unclear, and the impact of DD in patients diagnosed with CC on disease-free survival (DFS) and overall survival (OS) is unknown. National Surgical Adjuvant Breast and Bowel Project (NASBP) protocol C-06 is a clinical trial comparing oral uracil/tegafur/leucovorin with 5-fluorouracil/leucovorin in patients with resected stage II/III carcinoma of the colon. PATIENTS AND METHODS: The NASBP enrolled 1,608 patients who had undergone potentially curative resection for stage II/III colon cancer from 256 medical sites between February 14, 1997, and March 31, 1999. RESULTS: Pathology reports from 1561 eligible patients retrospectively reviewed for the presence of DD revealed that 160 (10.2%) had this disease. The median ages of patients with CC and DD and without DD were 67 and 61 years, respectively (P < 0.05). The majority of patients were white, and Hispanic patients were better represented in the group with DD (P < 0.05). Colon cancer was located in the rectosigmoid in 46.88% of patients with DD and in 31.92% of patients without DD (P < 0.05). A baseline diagnosis of DD made no significant contribution to DFS or OS without adjustment for confoundin factors (P = 0.2 and P = 0.32, respectively) or adjusted for Dukes classification and age (P = 0.49 and P = 0.68, respectively). CONCLUSION: The prevalence of DD in patients diagnosed and treated for CC was 10.2%. Patients with CC with and without DD differed from each other with respect to age, tumor location, and ethnicity. There was no negative impact of having DD on DFS and OS in patients treated for stage II/III CC.

Adult↗
PubMed2005

Inflammation and remodelling in the ageing airway.

WHAT WE NEED TO KNOW: What changes occur in atopic and non-atopic airway inflammation in asthma with increasing age? What is the relationship between wound healing and airway remodelling in older subjects? What is the response to anti-inflammatory therapy in older subjects? What is the basis of the "overlap syndrome" with chronic obstructive pulmonary disease in older people with asthma, in whom smoking contributes to airway disease? WHAT WE NEED TO DO: Identify the contribution of immunological mechanisms to asthma in ageing. Determine the extent to which airway remodelling plays a role in airflow obstruction in older people, specifically reversible components. Reduce the impact of smoking in young people with asthma.

Aged↗
PubMed2005

Hospital rules-based system: the next generation of medical informatics for patient safety.

PURPOSE: The hospital rules-based system (HRBS) and its subsystems at a major medical center are described. SUMMARY: The HRBS was implemented at the Mayo Clinic to rapidly identify and communicate crucial information to the clinician in order to optimize patient care. The system also enhances workload efficiency and improves documentation and communication. The system is used by the infectious-diseases division, pharmacy services, nutritional support services, infection control, and the nursing department. The six HRBS subsystems are Web-based programs that share a common structural design and integrate computerized information from multiple institutional databases. The integrated data are presented in a user-friendly format that improves the efficiency of data retrieval. Information, such as monitoring notes and intervention information, can be entered for specific patients. The subsystems use rules designed to detect suboptimal therapy or monitoring and identify opportunities for cost savings in a timely manner. CONCLUSION: The HRBS enhances the identification of drug-related problems while optimizing patient care and improving communication and efficiency at a major medical center.

Hospital Information Systems↗
PubMed2005

Rhinovirus infects primary human airway fibroblasts and induces a neutrophil chemokine and a permeability factor.

The events linking rhinovirus (RV) infection to airway symptoms are poorly understood. The virus initially infects airway epithelium followed by a vigorous inflammatory response that may entail spread of RV from epithelium to other cells in the airway wall. However, RV has fastidious growth characteristics and to date reproductive infection of primary cells other than human airway epithelium has not been confirmed. Airway fibroblasts are adjacent to and in contact with epithelial cells, play a key role in innate immune responses, and may participate in the evolution of inflammation. To investigate fibroblast actions, we first determined whether RV could infect and replicate in primary culture human lung fibroblasts. RV serotype 16 (RV16) was used to infect fibroblasts grown from lung tissue, and virus infection with replication was demonstrated by a combination of techniques. RT-PCR was used to show an increase in RV transcription; confocal microscopy demonstrated colocalization of the replicative form of RV genome (double-stranded RNA) and RV16 proteins; infectious virus was also recovered from the culture supernatant of infected fibroblasts. Functional consequences of RV infection were next examined. RV infection of fibroblasts was followed by an increase in epithelial neutrophil-activating peptide-78 (ENA-78) mRNA and protein. The permeability factor vascular endothelial growth factor (VEGF) was also induced over a similar time course. These data suggest that interactions between RV and human fibroblasts are feasible, may coordinate neutrophil chemoattraction with enhanced vascular permeability and that fibroblasts may contribute to inflammatory responses following RV infections.

Cells, Cultured↗