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1.  Cysteinyl Leukotriene Receptor-1 Antagonists as Modulators of Innate Immune Cell Function 
Journal of Immunology Research  2014;2014:608930.
Cysteinyl leukotrienes (cysLTs) are produced predominantly by cells of the innate immune system, especially basophils, eosinophils, mast cells, and monocytes/macrophages. Notwithstanding potent bronchoconstrictor activity, cysLTs are also proinflammatory consequent to their autocrine and paracrine interactions with G-protein-coupled receptors expressed not only on the aforementioned cell types, but also on Th2 lymphocytes, as well as structural cells, and to a lesser extent neutrophils and CD8+ cells. Recognition of the involvement of cysLTs in the immunopathogenesis of various types of acute and chronic inflammatory disorders, especially bronchial asthma, prompted the development of selective cysLT receptor-1 (cysLTR1) antagonists, specifically montelukast, pranlukast, and zafirlukast. More recently these agents have also been reported to possess secondary anti-inflammatory activities, distinct from cysLTR1 antagonism, which appear to be particularly effective in targeting neutrophils and monocytes/macrophages. Underlying mechanisms include interference with cyclic nucleotide phosphodiesterases, 5′-lipoxygenase, and the proinflammatory transcription factor, nuclear factor kappa B. These and other secondary anti-inflammatory mechanisms of the commonly used cysLTR1 antagonists are the major focus of the current review, which also includes a comparison of the anti-inflammatory effects of montelukast, pranlukast, and zafirlukast on human neutrophils in vitro, as well as an overview of both the current clinical applications of these agents and potential future applications based on preclinical and early clinical studies.
doi:10.1155/2014/608930
PMCID: PMC4058211  PMID: 24971371
2.  Inflammatory Pseudotumour of the Lung: A Case Report and Literature Review 
Case Reports in Radiology  2012;2012:214528.
We describe a patient with inflammatory pseudotumour of the lung. He was a young man who presented with haemotysis and the chest X-ray and computerized tomography were indicative of a nonbenign lesion in the right upper lobe. Excision biopsy confirmed the diagnosis of inflammatory myofibroblastic pseudotumour of the lung. This is a rare inflammatory nonneoplastic condition commonly affecting children and young adults.
doi:10.1155/2012/214528
PMCID: PMC3523579  PMID: 23304609
4.  Investigation of mycobacterial colonisation and invasion of the respiratory mucosa 
Thorax  2003;58(3):246-251.
Methods: The interaction of M avium complex, M tuberculosis, and M smegmatis with human respiratory tissue was investigated in an organ culture model with an air interface. Tissue was infected for intervals up to 14 days and assessed by scanning electron microscopy for adherent bacteria or cultured for recoverable bacteria.
Results: The mean number of adherent bacteria/mm2 (and the viable count of macerated tissue, cfu/ml) at 15 minutes, 3 and 24 hours, 7 and 14 days were: M avium complex 168 (153), 209 (136), 289 (344), 193 (313), 14140 (16544); M tuberculosis 30 (37), 39 (23), 48 (53), 1 (760), 76 (2186); M smegmatis 108 (176), 49 (133), 97 (81), 114 (427), 34 (58), (n=6). There was no significant change in morphology between infected and uninfected tissue or tissue infected with the different species over 14 days. The number of M avium complex on the mucosa and recovered from tissue increased over time (p=0.03). M tuberculosis decreased on the surface, but recoverable bacteria increased (p=0.01). M smegmatis numbers on the mucosa and recovered from tissue decreased. Sectioned tissue showed M avium complex and M tuberculosis in submucosal mucus glands and M tuberculosis penetrating epithelial cells in one experiment.
Conclusions: The initial adherence to the mucosa of the three species was similar, but after 14 days they varied in their interaction with the tissue in a manner compatible with their pathogenicity.
doi:10.1136/thorax.58.3.246
PMCID: PMC1746603  PMID: 12612305
5.  Effect of immunization with Freund's adjuvant and pneumolysin on histologic features of pneumococcal infection in the rat lung in vivo. 
Infection and Immunity  1992;60(11):4969-4972.
Immunization with Freund's adjuvant and pneumolysin and stimulation with Freund's adjuvant alone both reduced the severity of the pneumonia caused by injections of bacteria into the apical lobe bronchi of rats. Neither protocol influenced the incidence of pneumococcal bacteremia. Illness sufficiently severe to require sacrifice was delayed from 2.8 days in nonimmunized animals to 5.7 days in those immunized with Freund's adjuvant and pneumolysin (P < 0.05) and 4.5 days in those stimulated with Freund's adjuvant alone (P, not significant).
PMCID: PMC258258  PMID: 1399007
6.  Effect of Streptococcus pneumoniae on human respiratory epithelium in vitro. 
Infection and Immunity  1989;57(7):2006-2013.
A total of 11 of 15 Streptococcus pneumoniae culture filtrates and all five bacterial autolysates produced by cell death in the stationary phase caused slowed ciliary beating and disruption of the surface integrity of human respiratory epithelium in organ culture. This effect was inhibited by cholesterol and was heat labile and reduced by standing at room temperature but was stable at -40 degrees C. The activity was detected at the late stationary phase of culture and was associated with the presence of hemolytic activity. Gel filtration of a concentrated culture filtrate and autolysate both yielded a single fraction of approximately 50 kilodaltons which slowed ciliary beating and were the only fractions with hemolytic activity. Rabbit antiserum to pneumolysin, a sulfhydryl-activated hemolytic cytotoxin released by S. pneumoniae during autolysis, neutralized the effect of the culture filtrate on respiratory epithelium. Both native and recombinant pneumolysin caused ciliary slowing and epithelial disruption. Electron microscopy showed a toxic effect of pneumolysin on epithelial cells: cytoplasmic blebs, mitochondrial swelling, cellular extrusion, and cell death, but no change in ciliary ultrastructure. Recombinant pneumolysin (10 micrograms/ml) caused ciliary slowing in the absence of changes in cell ultrastructure. Release of pneumolysin in the respiratory tract during infection may perturb host defenses, allowing bacterial proliferation and spread.
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PMCID: PMC313834  PMID: 2731981
7.  Delayed pneumothorax after transbronchial lung biopsy. 
Thorax  1986;41(8):647-648.
PMCID: PMC460412  PMID: 3787546
8.  Observations on the relation of environmental and behavioral factors to the occurrence of otitis media among Indian children. 
Public Health Reports  1981;96(4):342-349.
Studies were conducted to assess the relation of environmental and behaviora factors to occurrence of acute suppurative otitis media (ASOM) among four populations of Indian children in Arizona. Episodes of ASOM were recorded for 1,428 children observed during the first year of life. Data obtained on the households and premises of these children included number of persons in the household, number of sleeping rooms, type of water supply and sewage disposal, type of heating and cooling, availability of electricity, method of infant feeding, distance to a health facility, and mother's education. The rates of ASOM for the four populations ranged from 1.1 to 2.2 attacks per child and differed significantly from each other, with one exception. The differences between populations apparently were not related to any of the factors evaluated. Additional analyses to evaluate the association of each factor with occurrence of ASOM included (a) a comparison of rates among children living in homes having each factor with rates among children living in homes lacking the factor, (b) a comparison of the frequency of each factor in homes of children who had no recorded attacks of ASOM with the frequency in homes of children who had three or more attacks (high-risk children), and (c) an evaluation of the relation between frequency of encounters for ASOM and the environmental factors. Results did not indicate that any environmental or behavioral factor observed was consistently or strongly associated with either the incidence of ASOM or the frequency of attacks. Similarly, no differences were apparent in the frequency of adverse environmental conditions in homes of infants with contrasting rates of ASOM. Rates of ASOM during the first year of life were not associated with either the presence or the absence of adverse environmental conditions.
PMCID: PMC1424226  PMID: 7255658
9.  Distribution of otitis media among four Indian populations in Arizona. 
Public Health Reports  1980;95(6):589-594.
More than 75 percent of the cases of acute suppurative otitis media (ASOM) among Indian children observed from May 1974 through March 1979 were experienced by preschool children. About 60 percent of the children observed during the first year of life had one or more attacks of ASOM, and 34 percent had two or more. Among those who had ASOM before their first birthday, 75 percent of the attacks occurred between 3 and 9 months of age. About 73 percent of the initial attacks were recorded during the first year of life among children observed from 3 to 5 years; almost 90 percent occurred before the second birthday. Approximately 75 percent of the second attacks occurred within 4 months of the first. More than 70 percent of the initial attacks before age 1 were followed by 1 or more subsequent attacks during the next 12 months. When the initial attack occurred during the second year of life, subsequent attacks were experienced by less than half as many children. Children at high risk of serious ear disease, including hearing loss, are characterized by having an attack of ASOM before their first birthday followed by a second attack within 4 months of the first. Efforts to control and prevent ASOM should selectively be directed toward this group.
PMCID: PMC1422794  PMID: 7433614

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