Abstract-We examined the roles of vitronectin and plasminogen activator inhibitor-1 (PAI-1) in neointima development.Neointima formation after carotid artery ligation or chemical injury was significantly greater in wild-type mice than in vitronectin-deficient (Vn Ϫ/Ϫ ) mice. Vascular smooth muscle cell (VSMC) proliferation did not differ between groups, suggesting that vitronectin promoted neointima development by enhancing VSMC migration. Neointima formation was significantly attenuated in PAI-1-deficient (PAI-1 Ϫ/Ϫ ) mice compared with control mice. Because intravascular fibrin may function as a provisional matrix for invading VSMCs, we examined potential mechanisms by which vitronectin and PAI-1 regulate fibrin stability and fibrin-VSMC interactions. Inhibition of activated protein C by PAI-1 was markedly attenuated in vitronectin-deficient plasma. The capacity of PAI-1 to inhibit clot lysis was significantly attenuated in vitronectin-deficient plasma, and this effect was not explained simply by the PAI-1-stabilizing properties of vitronectin. The adhesion and spreading of VSMCs were significantly greater on wild-type plasma clots and PAI-1-deficient plasma clots than on vitronectin-deficient plasma clots. We conclude that endogenous levels of vitronectin and PAI-1 enhance neointima formation in response to vascular occlusion or injury. Their effects may be mediated to a significant extent by their capacity to promote intravascular fibrin deposition and by the capacity of vitronectin to enhance VSMC-fibrin interactions.

At KGMC Lucknow, 168 pediatric cases with aural foreign bodies (FB) were reviewed. Most of the FB were self-inflicted and seen in children under 5 years of age (69.64%), within 24 hours (91.66%) of impaction. 86.30% of FB were seen to impact in external auditory canal (EAC) and their nature revealed predominance of nonvegetative inanimate FBs (43.45%). The TM perforation was encountered in only 6.54% of cases. If the FB is a living insect, it should be drowned before being manipulated. Syringing is the method of choice for a nonimpacted relatively small FB, even if it is vegetative. It is to be avoided in the 'potential' cases of external otitis or in cases with severely impacted wax. For a tightly wedged smooth rounded FB the hook and forceps are preferred in superficially and deep lying FBs respectively. A dissociate anaesthesia (ketamine) appears to be a better choice than general anaesthesia. An end-aural incision should be preferred over post-aural one and canalplasty for access of FB should be carried out wherever necessary. The presence of otorrhoea in cases of penetrating FB or aural myasis should be dealt on the lines of otitis media after removing the FB concerned.

CD14 is a lipopolysaccharide receptor known to be an important modulator of Th1-Th2 response during early childhood. Genetic association studies of the CD14 gene with asthma and atopic disorders have shown positive as well as negative results in different ethnic populations. The aim of this study was to test for association of C-159T functional promoter polymorphism with atopic asthma and serum IgE levels in northern and northwestern Indian populations. DNA was assayed for the CD14 C-159T polymorphism in a case-control study involving atopic asthmatics (n=187) and healthy normal controls (n=227), and in a family-based association study of 106 trios. The case-control study showed an association at the genotypic (P=0.0146) as well as the allelic level (P=0.0048). Moreover, we observed a deviation of allelic transmission from random proportions (P=0.024) in the transmission disequilibrium test analysis. When we analyzed our results for serum total IgE levels, against this polymorphism, we observed a difference at the genotypic (P=0.0026) as well as at the allelic level (P=0.0016) in a case-control study, whereas no association in the quantitative transmission disequilibrium test analysis was obtained. These findings provide suggestive evidence of association of the CD14 gene locus with atopic asthma in northern and northwestern Indian populations.

Mutant alleles of MYH9 encoding a class II non-muscle myosin heavy chain-A (NMMHC-IIA) have been linked to hereditary megathrombocytopenia with or without additional clinical features that include sensorineural deafness, cataracts, and nephritis. To assess its biological role in the affected targets, particularly the inner ear, we have generated and characterized mice with Myh9 deficiency. These mice were generated using the XA136 ES cell line (BayGenomics, http://baygenomics.ucsf.edu/) carrying gene trap insertion in Myh9, within the intron flanking exons 4 and 5. Mice heterozygous for the Myh9 null allele, Myh9 +/- were expanded on C57BL/6J background. Intercross of the Myh9 +/- mice did not yield Myh9 -/- pups, indicating embryonic lethality, subsequently determined to occur at or before E7.5, thus precluding a post-natal analysis of the effects of complete Myh9 deficiency. The heterozygous mice were normal for their hearing, parameters of platelet integrity and renal function despite their Myh9 haplo-insufficiency. In addition, the age-dependent auditory threshold of the Myh9 +/- mice and their wild type littermates, spanning from 3 to 12 months of age, were similar indicating that Myh9 haplo-insufficiency does not contribute towards accelerated age-related hearing loss (AHL). The embryonic lethality associated with the complete Myh9 deficiency establishes a critical role for this non-muscle myosin in fetal development. The results of these studies do not support the Myh9 haploinsufficiency as a pathogenic factor in the etiology of auditory dysfunction.

Angiofibromas of the post nasal space have the potential to extend in all directions along predetermined pathways with a definite mode and chronological pattern. In order to understand their clinical behaviour, methods of treatment and prognosis, a system of clinical staging based on conventional and tomographic observations has been found useful in this series of cases. The classification has been evolved according to the extent of the tumour involvement but also the age of onset, duration, size and area of encroachment including the surgical approach and consequent prognosis. Deficiencies in the earlier classifications are discussed.