A specialized tissue type, the keratinizing epithelium, protects terrestrial mammals from water loss and noxious physical, chemical and mechanical insults. This barrier between the body and the environment is constantly maintained by reproduction of inner living epidermal keratinocytes which undergo a process of terminal differentiation and then migrate to the surface as interlocking layers of dead stratum corneum cells. These cells provide the bulwark of mechanical and chemical protection, and together with their intercellular lipid surroundings, confer water-impermeability. Much of this barrier function is provided by the cornified cell envelope (CE), an extremely tough protein/lipid polymer structure formed just below the cytoplasmic membrane and subsequently resides on the exterior of the dead cornified cells. It consists of two parts: a protein envelope and a lipid envelope. The protein envelope is thought to contribute to the biomechanical properties of the CE as a result of cross-linking of specialized CE structural proteins by both disulfide bonds and N(epsilon)-(gamma-glutamyl)lysine isopeptide bonds formed by transglutaminases. Some of the structural proteins involved include involucrin, loricrin, small proline rich proteins, keratin intermediate filaments, elafin, cystatin A, and desmosomal proteins. The lipid envelope is located on the exterior of and covalently attached by ester bonds to the protein envelope and consists of a monomolecular layer of omega-hydroxyceramides. These not only serve of provide a Teflon-like coating to the cell, but also interdigitate with the intercellular lipid lamellae perhaps in a Velcro-like fashion. In fact the CE is a common feature of all stratified squamous epithelia, although its precise composition, structure and barrier function requirements vary widely between epithelia. Recent work has shown that a number of diseases which display defective epidermal barrier function, generically known as ichthyoses, are the result of genetic defects of the synthesis of either CE proteins, the transglutaminase 1 cross-linking enzyme, or defective metabolism of skin lipids.
Animal ; Cell Membrane/metabolism ; Epidermis/metabolism* ; Epidermis/chemistry* ; Human ; Ichthyosis/metabolism ; Ichthyosis/genetics ; Keratinocytes/metabolism* ; Keratinocytes/chemistry ; Membrane Lipids/metabolism* ; Membrane Proteins/metabolism* ; Protein-Glutamine gamma-Glutamyltransferase/metabolism

PURPOSE: The aim of the present study was to evaluate the clinical characteristics of the primary Epstein-Barr virus (EBV) hepatitis with elevation of both serum alkaline phosphatase (ALP) and gamma-glutamyltransferase (gamma-GT) levels in children. MATERIALS AND METHODS: A retrospective study was performed by reviewing of the medical records of 36 patients who were diagnosed with primary EBV hepatitis. The patients were divided into 2 groups: patients with elevated serum ALP and gamma-GT levels (group 1) and patients without (group 2). RESULTS: The classic features of infectious mononucleosis (fever, pharyngitis and/or tonsillitis, and cervical lymphadenitis) were seen in 20 (57.1%) of group 1 patients and 18 (50.0%) of group 2 patients. Hepatitis with elevated serum ALP and gamma-GT levels were present in 14 (38.9%) of the all patients. Of these patients, Jaundice occurred in only 2 (5.6%). The mean levels of aspartate aminotransferase and alanine aminotransferase (ALT) as well as the number of patients with ALT greater than 400 IU/L were significantly different between the groups (177 IU/L vs. 94 IU/L, 418 IU/L vs. 115 IU/L, and 50.0% vs. 13.6%; p=0.001, p=0.001, p=0.026, respectively). The mean duration of elevated serum ALT levels was 17.5 days in group 1 and 9.0 days in group 2 (p=0.013). All patients recovered fully without any chronic or serious complications. CONCLUSION: Primary EBV hepatitis with predominant biochemical abnormalities of the elevation of ALP and gamma-GT is frequent and mostly anicteric. This may represent a benign disease, but a delay in recovery of liver function as well.
Alkaline Phosphatase/genetics/*metabolism ; Child ; Child, Preschool ; Female ; Hepatitis/*enzymology/*pathology/virology ; Herpesvirus 4, Human/*pathogenicity ; Humans ; Infant ; Male ; gamma-Glutamyltransferase/genetics/*metabolism

Transglutaminase (TGase) isoenzymes are involved in the process of the differentiation and cornification of keratinocytes in the epidermis. This study investigates the presence and localization of three TGase isoenzymes to elucidate the nature and differentiation status of the squamous epithelium in human aural cholesteatoma. Twenty cholesteatoma specimens were used. The presence and localization of three TGase isoenzymes were studied by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. mRNA expression of three TGase isoenzymes were detected in the tested cholesteatomas with variable levels. The immunohistochemical staining patterns of three TGase isoenzymes showed variations within specimens, relating to keratinizing activity. TGase K is the most abundant among three isoenzymes. Keratinizing epithelium of cholesteatoma have similar expression profiles of TGase isoenzymes with those of epidermis of the skin. Other areas, particularly those showing non-keratinizing epithelium, showed weak immunostaining of TGase E and C, suggesting its different maturation status from keratinizing epithelium. The results of this study indicate that epithelium of cholesteatoma undergoes same direction of maturation and differentiation characteristics as the epidermis of skin, evidenced by similar expressions of TGases both in mRNA level and immunohistochemistry.
Cell Differentiation ; Cholesteatoma, Middle Ear/genetics ; Cholesteatoma, Middle Ear/enzymology* ; Comparative Study ; Diagnosis, Differential ; Epidermis/enzymology ; Epithelial Cells/enzymology ; Human ; Immunohistochemistry ; Isoenzymes/metabolism ; Isoenzymes/genetics ; Keratinocytes/enzymology ; Protein-Glutamine gamma-Glutamyltransferase/metabolism* ; Protein-Glutamine gamma-Glutamyltransferase/genetics ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo explore the relationship between the alteration in GGT mRNA expression and the development of HCC.

METHODSThree GGT mRNA types (F, H, and P) in normal liver tissues, diseased liver tissues without HCC, cancerous and noncancerous tissues from livers with HCC, and noncancerous tissues from livers with metastatic tumor were tested by RT-PCR.

RESULTSIn normal livers, the main type of GGT mRNA was type F. In liver diseases but not HCC, the distribution of the type GGT mRNA was nearly the same as in normal livers. The prevalence of type H was significantly higher in both cancerous and noncancerous tissues of livers with HCC than in livers without HCC (P<0.05). The prevalence of type F in cancerous tissues was significantly lower than that in livers without HCC (P<0.05).

CONCLUSIONSThe GGT mRNA expression in the human liver will shift from type F to type H during the development of HCC. The fragment analysis of GGT genes may be a sensitive assay to detect hepatic cell canceration.

Carcinoma, Hepatocellular ; enzymology ; genetics ; pathology ; Female ; Gene Expression Regulation, Enzymologic ; Humans ; Liver ; enzymology ; metabolism ; pathology ; Liver Diseases ; enzymology ; genetics ; pathology ; Liver Neoplasms ; enzymology ; genetics ; pathology ; Male ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; gamma-Glutamyltransferase ; genetics