PubMed · 7040652
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M Adinolfi, J Zenthon. 1982. Complement and disease: a review.. https://doi.org/10.1177/014107688207500211
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The key role of gp120 in the cellular entry of HIV makes this glycoprotein an attractive target for new drugs. Various polyanions bind to the positively charged V3 loop of gp120. Here, we consider a series of anionic porphyrins bearing two sulfonate groups and two carboxylic chains with various degree of esterification. These molecules carry an overall negative charge between 4 and 2. Upon activation by light, these compounds, known as photosensitizers, produce highly reactive oxygen species able to damage amino acid chains. The interactions of these molecules with the V3 loop and a positively charged area in the C5 region were investigated in the dark by using specific antibodies and ELISA protocols. Competitive inhibition of the anti-V3 antibody was observed with an increased efficiency for the esterified compounds. No evidence for binding to the C5 region was found. In contrast, when gp120 was irradiated with light in presence of the porphyrin prior to the addition of the antibody, strong inhibition of the anti-C5 antibody was observed revealing irreversible photo-damages in this region. No effect on the V3 loop was observed. Irradiations at two wavelengths made it possible to identify porphyrin monomers as the photoactive forms despite the presence of large excess of dimers in the incubation solution. It is suggested that porphyrins bound to the V3 loop could produce photo-damages at some distance, in particular within the C5 region that contains several photosensitive amino acids.
Most of the data on the pathogenesis of asthma is based on information obtained through bronchial biopsies and bronchoalveolar lavage in adults and young adults. Ethical considerations linked to the invasive nature of airway endoscopy have limited the studies on the pathophysiology of asthma in infancy and early childhood. Although there is evidence that an asthma-like inflammation, with increased inflammatory cells and thickening of the lung basement membrane, may be present also at a very early age, clinical and epidemiologic studies suggest that asthma manifestations in preschool children may significantly differ from those observed in older subjects. In western countries, the vast majority of infants and young children has episodic (or intermittent) asthma, and the exacerbations generally defined "wheezing episodes" occur more frequently with a seasonal pattern being usually related to acute viral infections. There is strong epidemiological evidence that approximately 2/3 of all children who wheeze because of viral infections in early life (and are not atopic) have a transient condition that tends to disappear during early school years. All respiratory viruses may be implicated in the wheezing episodes, the principal being respiratory syncytial virus (RSV) and, with a lower frequency, adenovirus and parainfluenza viruses during the first 3 years of life, and rhinoviruses after that age. Infants and preschool children have on average 6-8 "colds" per year, but the illness tends to be limited to the upper respiratory tract alone in a considerable proportion of individuals, without causing symptomatic involvement of the lower respiratory tract. The variety of factors determining the different outcomes are only partially known, but complex interactions between the intrinsic pathogenicity of the virus and host factors, including the socio-economic conditions of the family, are central to define the type of manifestations and the severity of the process.