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Query: UMLS:C0004623 (bacterial infection)
 15,226 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is a growing body of evidence from clinical and epidemiologic studies that in utero exposure to infection plays an important role in the genesis of fetal or neonatal injury leading to cerebral palsy and chronic lung disease. Thus, after chorioamnionitis the incidence of immature neonates with periventricular white matter damage and periventricular or intraventricular hemorrhage is significantly elevated. Recent clinical and experimental data support the hypothesis that a fetal inflammatory response links antenatal infection with brain white matter damage and subsequent motor handicap. A variety of studies support the view that cytokines released during intrauterine infection directly cause injury to the immature brain. In this review, we provide evidence that in utero exposure to bacterial infection can severely alter fetal cardiovascular function, resulting in dysregulation of cerebral blood flow and subsequent hypoxic-ischemic brain injury.
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PMID:Infection-related perinatal brain injury: the pathogenic role of impaired fetal cardiovascular control. 1466 57

Although there has been impressive progress in the elucidation of the genetic and molecular basis of cystic fibrosis (CF), the pathogenesis of CF lung disease remains obscure. The elucidation of the pathogenesis of CF lung disease requires both a full description of normal innate airway defence and how absent function of the cystic fibrosis transmembrane regulator protein (CFTR) adversely perturbs this activity. Recent data have linked the abnormal ion transport properties of CF airway epithelia to depleted airway surface liquid (ASL) volume, reflecting the combined defects of accelerated Na+ transport and the failure to secrete Cl-. Depletion of a specific compartment of the ASL, i.e. the periciliary liquid (PCL), appears to abrogate both cilia-dependent and cough clearance. Subsequent to PCL depletion, mucus adheres to airway surfaces and persistent mucin secretion generates the formation of "thickened" mucus plaques and plugs, which become the nidus for bacterial infection. The paucity of liquid in these plaques/plugs, and the hypoxia in this environment, appear to promote biofilm bacterial infection. Therapeutic agents that restore airway surface liquid volume, i.e. blockers of Na+ transport, initiators of Cl- transport and osmolytes, are reviewed, as are strategies that may be required to use volume-restoring agents safely in patients with cystic fibrosis.
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PMID:New concepts of the pathogenesis of cystic fibrosis lung disease. 1473 47

Boutonneuse fever is a bacterial infection caused by Rickettsia conorii. It occurs mainly in countries around the Mediterranean basin. Most cases are benign. However severe forms with major morbidity and a high mortality risk have been described. Severe forms often involve altered mental status, hepatic cytolysis, hemostatic disturbances, pneumopathy, and kidney failure. The causes of renal complications are unclear. The purpose of this report is to describe three cases of boutonneuse fever associated with acute kidney failure due to different underlying mechanisms, i.e., acute renal function failure, acute tubular necrosis, and extracapillary glomerulonephritis. While the first two mechanisms of kidney failure have been reported frequently in association with Boutonneuse fever, extracapillary glomerulonephritis has, to our knowledge, been mentioned only once. This case supports speculation that Rickettsia conorii has a toxic effect on glomeruli.
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PMID:[Acute renal insufficiency in Boutonneuse Mediterranean fever: description of three cases]. 1522 60

The existence of mucus plugs, containing mucins, bacteria, and neutrophils, blocking the lower airways in the lung of cystic fibrosis (CF) patients has raised the possibility that production of "abnormal" mucins is a critical characteristic of this disease. The molecular nature, if any, of this abnormality is unknown. Recent studies suggest that CF lung disease progression is characterized by an early phase in which airway surface liquid (ASL) increased dehydration is accompanied by altered pH and levels of reduced glutathione (GSH). In a later phase, bacterial infection and neutrophil invasion lead to increased ASL of concentrations myeloperoxidase and hypochlorous acid (HOCl). Independent studies indicate that gel-forming mucins, the key components of airway mucus, form disulfide-linked polymers through a pH-dependent, likely self-catalyzed mechanism. In this article, we present the hypothesis that increased mucus concentration (dehydration) and altered pH, and levels of GSH, myeloperoxidase, and/or HOCl result in the extracellular formation of additional interchain bonds among airway mucins. These novel interactions would create an atypical mucin network with abnormal viscoelastic and adhesive properties.
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PMID:Reevaluating gel-forming mucins' roles in cystic fibrosis lung disease. 1547 8

The progression of lung disease in cystic fibrosis (CF) is characterized by an exuberant inflammatory response mounted by the respiratory epithelium that is further exacerbated by bacterial infection. Recent studies have demonstrated upregulation of nuclear factor-kappaB (NF-kappaB) in response to infection in genetically modified cell culture models, which is associated with expression of interleukin (IL)-8. Using human airway epithelial cells grown in primary culture, we examined in vitro activation of NF-kappaB in cells isolated from five CF (DeltaF508/DeltaF508) and three non-CF (NCF) patients in response to Pseudomonas aeruginosa. Immunofluorescence, gel-shift, and immunoblot assays demonstrated a rapid translocation of NF-kappaB subunits (p50 and p65) to the nucleus in both CF and NCF cell cultures. However, nuclear extracts from CF cells both before and following P. aeruginosa stimulation revealed elevated NF-kappaB activation compared with NCF cells. Additionally, elevated nuclear levels of the NF-kappaB inhibitor IkappaBalpha were detected in nuclei of CF cells after P. aeruginosa stimulation, but this increase was transient. There was no difference in IL-8 mRNA levels between CF and NCF cells early after stimulation, whereas expression was higher and sustained in CF cells at later times. Our results also demonstrated increased baseline translocation of NF-kappaB to nuclei of primary CF epithelial cell cultures, but intranuclear IkappaBalpha may initially block its effects following P. aeruginosa stimulation. Thus, IL-8 mRNA expression was prolonged after P. aeruginosa stimulation in CF epithelial cells, and this sustained IL-8 expression may contribute to the excessive inflammatory response in CF.
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PMID:NF-kappaB activation and sustained IL-8 gene expression in primary cultures of cystic fibrosis airway epithelial cells stimulated with Pseudomonas aeruginosa. 1551 93

In cystic fibrosis (CF), inflammation is caused by persistent bacterial infection from Pseudomonas aeruginosa and Burkholderia cenocepacia in the lung and is characterised by the persistent infiltration of massive numbers of neutrophils which leads to lung injury. The aim of this present study was to investigate the effects of CF exacerbations on the reactivity of peripheral blood neutrophils compared to data from a normal healthy control population. Peripheral blood neutrophils were isolated from control subjects and CF patients before and after an exacerbation of their lung disease. Isolated neutrophils were stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol 12-myristate 13-acetate (PMA) and the rate of superoxide generation and elastase activity measured and compared with neutrophils from healthy age-matched controls. Neutrophils from CF patients spontaneously generated higher levels of superoxide after resolution of the exacerbation compared to control neutrophils. The stimulated generation of superoxide from control neutrophils was not significantly different from neutrophils isolated from CF patients either before or after resolution of the CF exacerbation. Neutrophils from CF patients spontaneously released more elastase than control neutrophils but released less elastase than control neutrophils in response to fMLP. The stimulated release of elastase from neutrophils was not significantly different before compared to after resolution of the exacerbation. Neutrophils from CF patients displayed a different pattern of response than those from control subjects; however, CF exacerbations did not appear to modulate neutrophil function.
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PMID:Effect of cystic fibrosis exacerbations on neutrophil function. 1568 55

Submucosal glands are abundant (approximately 1 gland/mm2) secretory structures in the tracheobronchial airways of the human lung. Because submucosal glands express antibacterial proteins, it has been proposed that they contribute to lung defense. However, this concept is challenged by the fact that mice do not have submucosal glands in their bronchial airways, yet are quite resistant to bacterial lung infection. The contribution of airway submucosal glands to host defense is also debated as a pathophysiologic component of cystic fibrosis lung disease. Here, we asked whether submucosal glands protect airways against bacterial infection. By comparing tracheal xenograft airways with and without glands, we found that the presence of glands enhanced bacterial killing in vivo and by airway secretions in vitro. Moreover, immunodepletion studies suggested that lysozyme is a major antibacterial component secreted by submucosal glands. These studies provide evidence that submucosal glands are a major source of antibacterials critical for maintaining sterile airways.
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PMID:Lysozyme secretion by submucosal glands protects the airway from bacterial infection. 1574 32

Cystic fibrosis (CF) lung disease is characterized by persistent lung infection. Thickened (concentrated) mucus in the CF lung impairs airway mucus clearance, which initiates bacterial infection. However, airways have other mechanisms to prevent bacterial infection, including neutrophil-mediated killing. Therefore, we examined whether neutrophil motility and bacterial capture and killing functions are impaired in thickened mucus. Mucus of three concentrations, representative of the range of normal (1.5 and 2.5% dry weight) and CF-like thickened (6.5%) mucus, was obtained from well-differentiated human bronchial epithelial cultures and prepared for three-dimensional studies of neutrophil migration. Neutrophil chemotaxis in the direction of gravity was optimal in 1.5% mucus, whereas 2.5% mucus best supported neutrophil chemotaxis against gravity. Lateral chemokinetic movement was fastest on airway epithelial surfaces covered with 1.5% mucus. In contrast, neutrophils exhibited little motility in any direction in thickened (6.5%) mucus. In in vivo models of airway mucus plugs, neutrophil migration was inhibited by thickened mucus (CF model) but not by normal concentrations of mucus ("normal" model). Paralleling the decreased neutrophil motility in thickened mucus, bacterial capture and killing capacity were decreased in CF-like thickened mucus. Similar results with each mucus concentration were obtained with mucus from CF cultures, indicating that inhibition of neutrophil functions was mucus concentration dependent not CF source dependent. We conclude that concentrated ("thick") mucus inhibits neutrophil migration and killing and is a key component in the failure of defense against chronic airways infection in CF.
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PMID:Reduced three-dimensional motility in dehydrated airway mucus prevents neutrophil capture and killing bacteria on airway epithelial surfaces. 1600 10

Patients with pulmonary insufficiency due to scleroderma have long been considered suboptimal candidates for lung transplantation. This has been supported by small single-center experiences that did not reflect the entire U.S. experience. We sought to evaluate the outcome of patients with scleroderma who underwent lung transplantation. We conducted a retrospective review of 47 patients with scleroderma who underwent lung transplantation at 23 U.S. centers between 1987 and 2004 and were reported to the United Network for Organ Sharing. Women constituted 57% of the patients. The mean age was 46 years. Twenty-seven patients received single lung transplants (57%), and the remaining received double lung transplants. The mean cold ischemia time was 4.1 hours. There were 7 early deaths (< or =30 days) and 17 late deaths (> 30 days). The causes of early death were primary graft failure and a cardiac event in two patients each and bacterial infection and stroke in one patient each. Late mortality was due to infection in seven patients, respiratory failure in three, malignancy in two, and multisystem organ failure, rejection, pulmonary hypertension, and a cardiac event in one patient each. The causes of early and late death were not recorded for two patients. One patient received a second transplant owing to graft failure of the first. Twenty-three patients (49%) were alive at a mean follow-up of 24 months. The Kaplan-Meier 1- and 3-year survival rates were 67.6% and 45.9% respectively, which are not significantly different from those of 10,070 patients given transplants for other lung conditions during the same period (75.5% and 58.8% respectively, P = 0.25). Donor gender, recipient's age, and type of transplant did not affect survival. In carefully selected patients with scleroderma who have end-stage lung disease, lung transplantation is a valid life-saving therapeutic option. Available data suggest acceptable short-term morbidity and mortality and a long-term survival similar to that of patients given transplants for other lung conditions.
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PMID:Outcomes of lung transplantation in patients with scleroderma. 1622 54

Cystic fibrosis (CF) is caused by a defect in the CF transmembrane conductance regulator (CFTR) protein that functions as a chloride channel. Dysfunction of the CFTR protein results in salty sweat, pancreatic insufficiency, intestinal obstruction, male infertility, and severe pulmonary disease. Most of the morbidity and mortality of CF patients results from pulmonary complications. Differences in susceptibility to bacterial infection and variable degree of CF lung disease among CF patients remain unexplained. Many phenotypic expressions of the disease do not directly correlate with the type of mutation in the Cftr gene. Using a unique CF mouse model that mimics aspects of human CF lung disease, we analyzed the differential gene expression pattern between the normal lungs of wild-type mice (WT) and the affected lungs of CFTR knockout mice (KO). Using microarray analysis followed by quantitation of candidate gene mRNA and protein expression, we identified many interesting genes involved in the development of CF lung disease in mice. These findings point to distinct mechanisms of gene expression regulation between mice with CF and control mice.
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PMID:Distinct pattern of lung gene expression in the Cftr-KO mice developing spontaneous lung disease compared with their littermate controls. 1641 21


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