bromochloroacetic-acid and Blepharitis

Hay-Wells syndrome, also known as ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome (OMIM 106260), is a rare autosomal dominant disorder characterized by congenital ectodermal dysplasia, including alopecia, scalp infections, dystrophic nails, hypodontia, ankyloblepharon and cleft lip and/or cleft palate. This constellation of clinical signs is unique, but some overlap can be recognized with other ectodermal dysplasia syndromes, for example ectrodactyly--ectodermal dysplasia--cleft lip/palate (EEC; OMIM 604292), limb--mammary syndrome (LMS; OMIM 603543), acro-dermato-ungual-lacrimal-tooth syndrome (ADULT; OMIM 103285) and recessive cleft lip/palate--ectodermal dysplasia (CLPED1; OMIM 225060). We have recently demonstrated that heterozygous mutations in the p63 gene are the major cause of EEC syndrome. Linkage studies suggest that the related LMS and ADULT syndromes are also caused by mutations in the p63 gene. Thus, it appears that p63 gene mutations have highly pleiotropic effects. We have analysed p63 in AEC syndrome patients and identified missense mutations in eight families. All mutations give rise to amino acid substitutions in the sterile alpha motif (SAM) domain, and are predicted to affect protein--protein interactions. In contrast, the vast majority of the mutations found in EEC syndrome are amino acid substitutions in the DNA-binding domain. Thus, a clear genotype--phenotype correlation can be recognized for EEC and AEC syndromes.

Topics: Abnormalities, Multiple; Amino Acid Sequence; Ankylosis; Base Sequence; Binding Sites; Blepharitis; Child; Cleft Lip; Cleft Palate; DNA; DNA Mutational Analysis; DNA-Binding Proteins; Female; Filaggrin Proteins; Genes, Tumor Suppressor; Heterozygote; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Male; Membrane Proteins; Molecular Sequence Data; Mutation, Missense; Phosphoproteins; Protein Structure, Tertiary; Sequence Alignment; Sequence Homology, Amino Acid; Skin; Syndrome; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

In contrast to wild-type mice, genetically engineered Mucin1 (Muc1) null animals display a marked propensity for development of blepharitis and conjunctivitis. Molecular approaches confirmed the presence of Muc1 mRNA and protein in the conjunctival tissue of wild-type mice and identified the bacterial species in Muc1 null symptomatic mice.. Muc1 null animals housed in a conventional facility were examined for visually apparent inflammation of the eye and surrounding tissue. Blood taken from overtly affected animals was assayed for antibodies to common murine viral agents. Swabs of infected eyes and whole eye preparations were used to detect and speciate bacterial pathogens. Frozen sections of whole eye, lid margin, and Harderian gland were immunostained with antibodies to Muc1 and cytokeratin 14, both epithelial cell markers. Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) were performed on RNA isolated from conjunctiva and Harderian gland of wild-type mice to compare relative levels of transcript.. Student's unpaired t-test performed on the eye inflammation frequency of Muc1 null mice confirmed a statistical significance (P < 0.01) when compared to wild-type background animals housed in the same room. Analysis of blood samples from affected Muc1 null animals detected no common murine viral pathogens. Bacterial analysis of conjunctival swabs and whole eye preparations demonstrated the presence of coagulase-negative Staphylococcus, Streptococcus type alpha, and Corynebacterium group G2. Muc1 antibody staining of wild-type sections revealed the presence of Muc1 on conjunctival goblet and non-goblet cells and on the epithelium of the Harderian gland. Serial sections stained with cytokeratin 14 antibody confirmed the epithelial nature of cells expressing the Muc1 protein. RNA from conjunctiva and Harderian gland subjected to RT-PCR and northern blot analysis showed an abundance of Muc1 transcript in these tissues.. Muc1 mRNA and protein are present in murine conjunctival and Harderian gland epithelia. Animals lacking Muc1 mRNA and protein are predisposed to developing eye inflammation when compared to wild-type animals with an intact Muc1 gene. Muc1 appears to play a critical protective role at the ocular surface, presumably by acting as a barrier to infection by certain bacterial strains.

Topics: Animals; Blepharitis; Conjunctiva; Conjunctivitis, Bacterial; Corynebacterium Infections; DNA Primers; Female; Fluorescent Antibody Technique, Indirect; Harderian Gland; Keratins; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mucin-1; Polymerase Chain Reaction; RNA, Messenger; Staphylococcal Infections; Streptococcal Infections

To determine whether there are specific cytologic features associated with primary Sjögren's syndrome (SS), the authors evaluated impression cytology specimens from three conjunctival sites (temporal bulbar [TB], inferior bulbar [IB], and inferior tarsal [IT]) from 38 SS eyes, 34 eyes of aqueous tear-deficient patients without SS, 35 eyes of seborrheic blepharitis patients, and 17 eyes of normal controls in a masked fashion. The following features were observed more frequently in SS eyes than in the eyes of the other groups: squamous metaplasia of the TB and IB (P less than 0.05), extensive (greater than 75%) goblet cell loss of the TB (P less than 0.05), mucous aggregates of the bulbar conjunctiva (P less than 0.05), and inflammatory cells intercalated with epithelial cells on the IT conjunctiva (P less than 0.06). The conjunctival inflammatory cell infiltrate correlated with the presence of extensive squamous metaplasia (P less than 0.01) in SS specimens. The inflammatory cells on the IT conjunctival epithelium were found to consist predominantly of T-lymphocytes by immunofluorescent staining of cytologic specimens from six eyes. Based on these findings, the authors speculated that conjunctival squamous metaplasia, in addition to aqueous tear deficiency, may be due to primary involvement of the dysfunctional immune system of SS.

Topics: Antibodies, Monoclonal; Antigens, CD; Antigens, Differentiation, B-Lymphocyte; Antigens, Differentiation, T-Lymphocyte; Blepharitis; CD3 Complex; Cell Adhesion Molecules; Chi-Square Distribution; Conjunctiva; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Lacrimal Apparatus Diseases; Lectins; Receptors, Antigen, T-Cell; Reproducibility of Results; Sialic Acid Binding Ig-like Lectin 2; Sjogren's Syndrome; T-Lymphocytes