Genetics reveals importance of platelet activating factor in asthma and possibly other inflammatory states.

Nadel, Jay A.

doi:10.1172/jci118720

Cited by 11 publications

(5 citation statements)

References 8 publications

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“…The efficacy shown by SR 27417A is at variance with the apparent negative data formerly observed with other classes of PAF antagonist, which did not provide definite evidence that PAF is a vital mediator in asthma [80]. This suggests that the effects of PAF antagonists should be investigated in other categories of asthma, for instance in patients with ASA [81], or that other functional outcomes, such as gas exchange markers, should be used to better identify the potential anti-oedema effect of the airways.…”

Section: Pathobiologymentioning

confidence: 72%

Acute severe asthma: pathophysiology and pathobiology of gas exchange abnormalities

Rodríguez-Roisín¹

1997

Eur Respir J

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Section: Pathobiologymentioning

confidence: 72%

Acute severe asthma: pathophysiology and pathobiology of gas exchange abnormalities

Rodríguez-Roisín¹

1997

Eur Respir J

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“…Nadel et al noted that even a small decrease in activity in heterozygotes could have a significant physiologic effect in the presence of inflammatory responses. A total of 27% of Japanese people are heterozygous for the mutation [86].…”

Section: Hemorrhagic Strokementioning

confidence: 99%

Genetics of stroke: a review of recent advances

Domingues‐Montanari¹,

Mendioroz²,

Río-Espínola³

et al. 2008

Expert Review of Molecular Diagnostics

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Stroke is a multifactorial disease responsible for nearly 10% of deaths each year in industrialized countries. While some monogenic forms of stroke have been described, the vast majority result from the common polygenic form of the disease. Progress in molecular genetics has allowed the identification, through genome-wide linkage analysis, of various candidate genes, including the genes encoding PDE4D and ALOX5AP. Since then, genetic research has been extensively performed from single candidate genes to whole-genome scan studies, in parallel with the development of high-throughput technologies in molecular diagnostics. Additionally, the safety and efficacy of tissue plasminogen activator, the only approved therapy for the acute phase of stroke, is modulated by genetic background associated with the occurrence of hemorrhagic transformations and with the revascularization of the cerebral arteries. In the near future, understanding the contribution of stroke genetic factors will lead to improvements in prevention and treatments for neurovascular diseases.

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“…In animal studies, PAF was implicated as an intermediate in asthma because receptor antagonists blocked physiological responses in protocols in which an immunological response was provoked (19,20). In summary, several independent lines of evidence indicate that PAF is involved in asthma as a mediator of positive feedback mechanisms during the inflammation that occurs in asthmatic airways (6).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, PAF causes the release of other inflammatory agonists from eosinophils, and eosinophils from asthmatics exhibit a markedly increased sensitivity to PAF compared with those from normal (nonasthmatic) subjects (5). PAF is produced by a variety of cell types involved in asthma, including alveolar macrophages, platelets, and eosinophils (6). However, the precise role that PAF plays in the pathophysiology of asthma is controversial, and multiple approaches have been used to examine its contribution (7).…”

Section: Introductionmentioning

confidence: 99%

Deficiency of platelet-activating factor acetylhydrolase is a severity factor for asthma

Stafforini¹,

Numao²,

Tsodikov³

et al. 1999

J. Clin. Invest.

119

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Asthma, a family of airway disorders characterized by airway inflammation, has an increasing incidence worldwide. Platelet-activating factor (PAF) may play a role in the pathophysiology of asthma. Its proinflammatory actions are antagonized by PAF acetylhydrolase. A missense mutation (V279F) in the PAF acetylhydrolase gene results in the complete loss of activity, which occurs in 4% of the Japanese population. We asked if PAF acetylhydrolase deficiency correlates with the incidence and severity of asthma in Japan. We found that the prevalence of PAF acetylhydrolase deficiency is higher in Japanese asthmatics than healthy subjects and that the severity of this syndrome is highest in homozygous-deficient subjects. We conclude that the PAF acetylhydrolase gene is a modulating locus for the severity of asthma. J. Clin. Invest. 103:989-997

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Genetics reveals importance of platelet activating factor in asthma and possibly other inflammatory states.

Cited by 11 publications

References 8 publications

Acute severe asthma: pathophysiology and pathobiology of gas exchange abnormalities

Acute severe asthma: pathophysiology and pathobiology of gas exchange abnormalities

Genetics of stroke: a review of recent advances

Deficiency of platelet-activating factor acetylhydrolase is a severity factor for asthma

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