In this immunohistochemical study, we characterized the cells infiltrating the stroma of acquired aural cholesteatomas in detail, using a panel of monoclonal antibodies directed against immune cell type-specific antigens, HLA class II antigens, and interleukin-2 receptor. For all antibodies used, normal ear skin was stained for comparison. The vast majority of the infiltrating cells was CD45-positive, ie, derived from bone marrow. Reactivity with anti-CD3 and anti-CD6 antibodies revealed an abundant infiltration of T lymphocytes beneath the squamous epithelium of cholesteatoma. The B lymphocyte-specific anti-CD19 and anti-CD22 antibodies detected only occasional positive cells. Hence, the cellular infiltrate in the stroma of aural cholesteatoma is made up primarily of T cells with macrophages scattered between them. Expression of HLA-DR was almost as high as that of CD45, whereas CD25-positive cells were detected in lower amounts. We infer that the majority of T cells and macrophages in the stroma of cholesteatoma are in an immunologically activated state. The characteristics of the infiltrating cell population suggest an antigen-driven process in cholesteatoma.

Antibodies, Monoclonal↗

PubMedDate not supplied

Possible autocrine growth stimulation of cholesteatoma epithelium by transforming growth factor alpha.

INTRODUCTION: Transforming growth factor alpha (TGF-alpha) is known to be produced by normal human keratinocytes and to stimulate their proliferation. The squamous epithelium of middle ear cholesteatoma is believed to exhibit hyperproliferative characteristics. This study was undertaken to determine if growth factors can be identified in cholesteatoma. MATERIALS AND METHODS: Cholesteatoma samples (n = 6) and retroauricular skin (n = 9) were obtained during surgery. Monoclonal antibody against epidermal growth factor (EGF) and TGF-alpha were evaluated in these specimens using immunohistochemical techniques. RESULTS: Epidermal growth factor receptor (EGF-R) was highly expressed in the basal layer of the epidermis, hair follicles, eccrine sweat glands, and the capillary system of normal skin. In the majority of cholesteatoma samples, expression of EGF-R was not confined to the basal layer but persisted in suprabasal cells of the stratum spinosum and stratum granulosum. In two cases, heterogenous standing was found in different parts of the same cryosection. Staining for TGF-alpha was consistently stronger in cholesteatoma than in normal skin, and encompassed all epithelial cell layers. Immune cells infiltrating the stroma of cholesteatoma stained positively for TGF-alpha. CONCLUSION: These data are consistent with autocrine stimulation of the squamous epithelium of cholesteatoma by TGF-alpha contributing to its unrestrained growth in the middle ear cavity.

Antibodies, Monoclonal↗

PubMedDate not supplied

High levels of fibronectin in the stroma of aural cholesteatoma.

PURPOSE: Because abundant fibronectin deposition is a hallmark of healing cutaneous wounds and provides a matrix for hyperproliferative and migratory epidermal cells, the distribution of fibronectin in aural cholesteatoma was investigated immunohistochemically. MATERIALS AND METHODS: A monoclonal antibody against the major cell binding domain of human fibronectin was used to stain 4-micron cryosections of cholesteatoma tissue by the alkaline phospatase-antialkaline phosphatase method. Section of normal retroauricular skin served as control. RESULTS: When processed in parallel, fibronectin staining was much stronger in the stroma of cholesteatoma than in normal dermis. The squamous epithelium of both tissues did not show any staining for fibronectin. CONCLUSIONS: These observations lend support to the view that the growth of cholesteatoma epithelium reflects an aberrant regenerative process.

Antibodies, Monoclonal↗

PubMedDate not supplied

Comparison of two endotracheal tube securement techniques on unplanned extubation, oral mucosa, and facial skin integrity.

OBJECTIVE: To determine the effect of 2 standard methods (i.e., twill tape versus adhesive tape) of securement on unplanned extubation, oral mucosa, and facial skin integrity of the orally intubated patient. DESIGN: A prospective, quasi-experimental design was used for the pilot study. SETTING: The setting for the pilot study included critical care units of 3 community hospitals and 1 veterans' hospital in a midwestern city. SUBJECTS: A total of 52 orally intubated adult subjects were enrolled in the study from the 4 clinical sites over a 6-month period of time. The participants in the study consisted of 30 men and 22 women. The subjects ranged in age from 22 to 85 years, with a mean age of 62.3 years. The mean length of intubation was 89.6 hours. OUTCOME MEASURES: The outcome measures of the study were (1) unplanned extubation, (2) oral mucosa status, and (3) facial skin integrity. INTERVENTIONS: Endotracheal tube securement with either the twill tape or the adhesive tape securement method. RESULTS: With use of multiple analysis of variances (MANOVA) and repeated analyses of variances (ANOVAs), there were no significant differences by time or type of endotracheal tube securement method on oral mucosa or facial skin integrity. A chi-square analysis demonstrated no significant association between the 2 types of endotracheal tube securement when comparing their efficacy in preventing unplanned extubation. CONCLUSION: The findings of this pilot study demonstrated both methods of endotracheal tube securement to be comparable in preventing unplanned extubation and in maintaining oral mucosa status and facial skin integrity.

Adhesives↗

PubMedDate not supplied

Analysis of the mutation to forskolin-resistance in Y1 adrenocortical tumor cells.

Forskolin reduced the plating efficiency of Y1 adrenocortical tumor cells in a concentration-dependent manner--more than 5-orders of magnitude at 10 uM forskolin and at least 6-orders of magnitude at 50 uM forskolin. This effect was related to the diterpene's ability to increase adenylate cyclase activity and adenosine 3',5'-monophosphate (cAMP) levels in Y1 cells. Stable, forskolin-resistant mutants were isolated following growth of Y1 cells for 3 to 4 weeks in the presence of 10 uM forskolin. These mutants were stable, were present in the population at a ratio of approximately 15 mutants per million cells and appeared to result from a defect in cAMP accumulation rather than cAMP action. The forskolin-resistant phenotype was associated with a reduced ability of forskolin to stimulate adenylate cyclase activity in intact cells and in cell homogenates. The adenylate cyclase system of forskolin-resistant mutants was responsive to NaF, but was virtually insensitive to corticotropin (ACTH). As determined by a modified fluctuation analysis, the forskolin-resistant phenotype arose by spontaneous mutation at a frequency consistent with a mutational event at a single genetic locus (2 mutants per million cells per generation). These results indicate that the mutation which rendered Y1 cells insensitive to ACTH likely was the same as that which led to forskolin-resistance. Furthermore, the mutation seemed to behave dominantly. Although the gene product altered by the mutation is unknown, it does not appear to be the catalytic subunit of the enzyme.

Adenylyl Cyclases↗