Human papilloma viruses and p53 mutations in normal,pre-malignant and malignant oral epithelia

HPV infections have been previously observed in oral cancers, and inactivation of the p53 gene has been shown to be one of the most common genetic alterations in human tumors. We examined 179 oral specimens from 70 individuals with histologic findings of either normal mucosa (n = 6) or oral disease that ranged from mild dysplasia to invasive squamous-cell carcinoma (n = 64) to determine the occurrence of both HPV infection and p53 mutations and their relationship with several clinical factors. HPV infection was detected by PCR amplification of viral DNA, and the presence of p53 mutations was assayed using the single-strand conformation polymorphism (SSCP)-PCR technique. HPV infection was found in 31% of individuals with oral disease and was not seen in healthy individuals. Mutations in exons 5, 6, 7 or 8 of the p53 gene were detected in 37.5% of patients with oral lesions and in a biopsy from 1 healthy individual who was a heavy smoker. Approximately one-third of lesions classified as pre-malignant (dysplasia and carcinoma in situ) and 42% of invasive carcinomas contained p53 mutations. The majority of these mutations were G:T transversions located within exons 7 and 8. Tumor tissues from 6 patients with oral lesions were found both to be HPV-16-positive and to contain p53 mutations; of these, 4 were poorly differentiated carcinomas that were diagnosed as late-stage disease. In this study, p53 mutations were detected in the early stages of cancer development. © 1996 Wiley-Liss, Inc.     

Soft-tissue lesions in children

This article reviews some of the benign and malignant oral soft-tissue swellings that occur in children, with an emphasis on their clinical presentation, etiology, histopathology, and treatment. These lesions include single and multiple nodules, reactive lesions, and benign and malignant neoplasms. Diseases discussed include reactive gingival swelling, generalized gingival fibromatosis, melanotic neuroectodermal tumor of infancy, fibromas, vascular lesions, salivary gland lesions, and infantile rhabdomyomas. Also covered are lesions that may present in multiples, such as neuromas, multiple endocrine neoplasia type 2b, neurofibromatosis, and human papilloma virus-related benign epithelial lesions. Benign but locally aggressive and malignant neoplasms are discussed, such as aggressive fibromatosis, myofibromatosis, fibrosarcoma, and rhabdomyosarcoma.     

A cohort study of <Emphasis Type="Italic">Plasmodium falciparum</Emphasis> infection dynamics in Western Kenya Highlands

Background  

The Kenyan highlands were malaria-free before the 1910s, but a series of malaria epidemics have occurred in the highlands of western Kenya since the 1980s. Longitudinal studies of the genetic structure, complexity, infection dynamics, and duration of naturally acquired Plasmodium falciparum infections are needed to facilitate a comprehensive understanding of malaria epidemiology in the complex Kenyan highland eco-epidemiological systems where malaria recently expanded, as well as the evaluation of control measures.     

Neutrophil-mediated damage to human gingival epithelial cells

Polymorphonuclear leukocytes (PMNs) have been implicated in the pathogenesis of inflammatory gingivitis and periodontitis. To further study the role of PMNs in mediating gingival injury, we cocultured these cells in vitro with monolayers of human gingival epithelial cells. Scanning electron microscopy revealed that the epithelial cells were homogeneous and SDS-PAGE/immunoblot analysis identified the presence of keratins K3, K13 and the K6/16 pair which authenticated the oral origin of the cells. Injury to the gingival cells was determined by scanning electron microscopy and measurement of cell detachment and cytolysis. Unstimulated PMNs produced minimal lysis or detachment, but PMNs stimulated by phorbol myristate acetate produced marked epithelial cell detachment without lysis, which was time- and PMN-dose-dependent. Supernatants of activated PMNs were similarly effective, indicating that the mediator was a stable soluble substance. Elastase and cathepsin G, two neutral proteases of PMN origin, produced time- and concentration-dependent detachment of gingival epithelial cells, suggesting that these enzymes may mediate this form of injury. In other studies, gingival epithelial cells were exposed to PMN myeloperoxidase (MPO), chloride and glucose plus glucose oxidase (GO) as a hydrogen peroxide (H2O2) generating system. The toxic oxygen species produced by this system caused lysis of the epithelial targets which was dependent on the duration of incubation and the concentrations of MPO and GO. Azide, an inhibitor of MPO, and catalase, a scavenger of H2O2, inhibited the lytic activity of this system. Scanning electron micrographs of gingival epithelial cells cocultured with activated PMNs showed lifting of the cells from the plating surface, while target cells attacked by the MPO system revealed extensive damage of cell membranes. These studies indicate that activated PMNs cause nonlytic detachment injury to gingival epithelial cells which may be mediated by digestion of their extracellular matrix by granule neutral proteases. Furthermore, PMN MPO is capable of generating toxic oxygen species which can lyse these epithelial cells. Collectively, these actions could have profound adverse effects on the function and integrity of the gingival epithelium.     

Synthesis of type VIII collagen by epithelial cells of human gingiva

The composition of the extracellular matrix produced by epithelial cells in contact with metabolically inert substrata was studied with antibodies specific for type VIII collagen. Type VIII collagen was present in the cell layer of cultured gingival epithelial cells, and at the epithelium-substratum interface of an explant culture model for junctional epithelium. Samples of the epithelial attachment apparatus (EAA) in vivo were collected by removing the junctional cells directly attached to the tooth (DAT cells) and the associated EAA matrix. The amount of material collected was sufficient for biochemical analysis of both intra- and extracellular components of the junctional cell-EAA complex. Immunological examination of the samples revealed that type VIII collagen was associated with epithelial cells forming the EAA in vivo . We suggest that this collagen type functions in the extracellular space as an attachment-promoting factor for gingival epithelial cells at the tooth surface.