Identification of a Keratin 4 mutation in a chemically induced mouse mutant that models white sponge nevus. (1/8)

With the goal of increasing the number of genetic entry points for studying physiologic processes and human disease, large-scale, systematic, chemical mutagenesis projects in mice have been initiated in several different centers. We have been studying mouse mutants that exhibit dominantly inherited defects in either skin and/or hair color. Here, we describe a bright coat color mutant, Bright coat color 1 (Bcc1), which develops light-colored hair at 4 weeks of age, and when homozygous exhibits oral leukoplakia and blistering, and growth retardation. We identified a missense mutation in mutant animals that predicts an N154S amino-acid substitution in the 1A domain of Keratin 4 (encoded by the Krt2-4 gene), a region known to be mutated in human patients with white sponge nevus (WSN). Bcc1 recapitulates the gross pathologic, histologic, and genetic aspects of the human disorder, WSN.  (+info)

The surface protein Srr-1 of Streptococcus agalactiae binds human keratin 4 and promotes adherence to epithelial HEp-2 cells. (2/8)

Streptococcus agalactiae is frequently the cause of bacterial sepsis and meningitis in neonates. In addition, it is a commensal bacterium that colonizes the mammalian gastrointestinal tract. During its commensal and pathogenic lifestyles, S. agalactiae colonizes and invades a number of host compartments, thereby interacting with different host proteins. In the present study, the serine-rich repeat protein Srr-1 from S. agalactiae was functionally investigated. Immunofluorescence microscopy showed that Srr-1 was localized on the surface of streptococcal cells. The Srr-1 protein was shown to interact with a 62-kDa protein in human saliva, which was identified by matrix-assisted laser desorption ionization-time-of-flight analysis as human keratin 4 (K4). Immunoblot and enzyme-linked immunosorbent assay experiments allowed us to narrow down the K4 binding domain in Srr-1 to a region of 157 amino acids (aa). Furthermore, the Srr-1 binding domain of K4 was identified in the C-terminal 255 aa of human K4. Deletion of the srr-1 gene in the genome of S. agalactiae revealed that this gene plays a role in bacterial binding to human K4 and that it is involved in adherence to epithelial HEp-2 cells. Binding to immobilized K4 and adherence to HEp-2 cells were restored by introducing the srr-1 gene on a shuttle plasmid into the srr-1 mutant. Furthermore, incubation of HEp-2 cells with the K4 binding domain of Srr-1 blocked S. agalactiae adherence to epithelial cells in a dose-dependent fashion. This is the first report describing the interaction of a bacterial protein with human K4.  (+info)

Repeated exposure to acid and bile selectively induces colonic phenotype expression in a heterogeneous Barrett's epithelial cell line. (3/8)

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Short-term Efficacy of Topical Immunosuppressive Agents on the Survival of Cultivated Allo-Conjunctival Equivalents. (4/8)

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Cultivated human conjunctival epithelial transplantation for total limbal stem cell deficiency. (5/8)

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Cell delivery with fixed amniotic membrane reconstructs corneal epithelium in rabbits with limbal stem cell deficiency. (6/8)

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Fascin and CK4 as biomarkers for esophageal squamous cell carcinoma. (7/8)

BACKGROUND: Several studies have suggested that fascin, cytokeratin 14 and cytokeratin 4 may have significant roles as biomarkers for the progression and survival of esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: This study performed immunohistochemistry in tissue microarrays, profiling premalignant lesions and invasive tumors. RESULTS: Fascin increased across the following states as follows: normal-appearing epithelium (26%) to dysplasia (46%) to ESCC (68%), while CK4 was undetectable in ESCC (0%) compared to normal-appearing epithelium (45%) or dysplasia (41%). CK14 was elevated and invariant in expression. In regression analyses, compared to normal-appearing epithelium, higher fascin expression was associated with a 36% increased risk of dysplasia (odds ratio=1.36) and a 56% increased risk of invasive ESCC (odds ratio=1.56). CONCLUSION: Expression of fascin is up-regulated in the transformation from normal-appearing epithelium, through dysplasia, into invasive carcinoma. Expression of CK4, CK14 and fascin did not correlate with patient survival. Fascin has a potential role as an early detection biomarker and CK4 as a tumor marker in ESCC.  (+info)

Conjunctival reconstruction with progenitor cell-derived autologous epidermal sheets in rhesus monkey. (8/8)

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