Advances in understanding cell interactions in tissue resorption. Relevance to the pathogenesis of periodontal diseases and a new hypothesis

Much of the connective tissue degradation that takes place in periodontal diseases is mediated by proteolytic enzymes. Previous studies have focused on the action of proteinases released by invading polymorphonuclear neutrophils and macrophages, and bacterial enzymes. In view of recent work establishing that resident connective tissue cells can be induced by cytokines to bring about the destruction of their own matrix, we propose a new hypothesis. In this we envisage that a critical step is the interaction of bacterial antigens with inflammatory cells, resulting in the production of a cytokine, interleukin-1. Our interpretation of in vitro evidence is that the loss of connective tissue attachment and bone matrix resorption in periodontal diseases is mediated by metalloproteinases such as collagenase and stromelysin released by cells of the periodontium. Such proteolytic destruction can be induced by interleukin-1, whose production may not be dependent on a specific microbial flora but may be triggered by a number of organisms. It is now clear that interleukin-1 has multiple actions on both immune and non-immune cells; these include the induction of lymphocyte differentiation and proliferation and the stimulation of bone and cartilage resorption, and prostaglandin and metalloproteinase synthesis by connective tissues. It seems likely that further knowledge about the production and function of this cytokine will have an increasing impact in many diseases that involve resorption, particularly since interleukin-1-like molecules can be produced by cell types other than monocytes/macrophages, including keratinocytes and fibroblasts.     

Human colonic goblet cells. Demonstration of distinct subpopulations defined by mucin-specific monoclonal antibodies.

We studied glycoprotein content of human colonic goblet cells, using a library of monoclonal antibodies (MAbs) directed against purified human colonic mucin (HCM). Using indirect immunofluorescence (IIF), we found that 17 of 23 anti-HCM MAbs stained some or all goblet cells of normal human colonic mucosa. We observed a variety of cellular staining patterns, including (a) diffuse (homogeneous) staining of intracellular mucin, (b) speckled (inhomogeneous) staining of mucin droplets, (c) peripheral staining of intracellular droplets, (d) cytoplasmic staining of goblet cells, and (e) apical (luminal) surface staining. Staining patterns were not associated with particular HCM species. In addition to variable patterns of IIF within individual cells, anti-HCM MAbs varied in the proportion of goblet cells stained. Some MAbs stained all goblet cells, while others stained a limited number of goblet cells. Although each goblet cell contained more than one type mucin, HCM species III, and IV and V appeared to exist in mutually exclusive goblet cell populations and it was possible to define at least seven subpopulations of goblet cells in colonic mucosa by their content of various combinations of HCM species. Anti-HCM MAbs stained goblet cells from other sites within the gastrointestinal tract to a varying extent. Anti-HCM MAbs also showed extensive cross-reactivity with rodent, rabbit, and monkey colonic mucosa. However, several anti-HCM MAbs stained only human colonic mucosa. These data show that human colonic mucosa contains discrete subpopulations of goblet cells that produce distinctive combinations of specific mucin glycoprotein species.     

Alveolar hydatid disease of the liver: Brief review and spectrum of adjacent organ invasion

The purpose of this study is to show the spectrum of adjacent organ invasion and to make a brief review of hepatic alveolar hydatid disease (AHD), using CT and MR imaging. We retrospectively reviewed CT and MR images of three patients with various adjacent organ invasions surgically and histologically proven to be AHD. Local invasion to right kidney and adrenal, right hemidiaphragm and lung were detected in one patient, right adrenal in another patient and gall bladder, duodenum, gastric wall and pancreas invasion in the other. AHD may rarely extend to the gall bladder, stomach, duodenum, pancreas, right adrenal and kidney, diaphragm, pleura and lung. The extension of the disease outside the liver is usually encountered in patients with large, peripherally located masses in the advanced stage of the disease.     

Long-term anticoagulant therapy in patients with coronary artery disease.

Secondary prevention of coronary events in coronary artery disease (CAD) patients with aspirin is generally accepted because of ease of administration, predictable safety, and proven efficacy. The use of long-term anticoagulant therapy with heparins, vitamin-K antagonists (VKAs), or thrombin inhibitors is, however, more controversial. During the last 40 years, several trials have been conducted in order to evaluate the role of anticoagulant therapy in patients with CAD as a protection against subsequent death and thrombo-embolic complications. The conducted trials are heterogeneous in many ways, concerning comparative medications, patient populations, endpoints and follow-up, which makes a standardized recommendation on the basis of these studies difficult. This review is an overview of the largest and best studies on this topic and discusses the scientific background for a possible use of VKA or an alternative anticoagulant treatment in CAD patients, looking at both the beneficial effects and the risk of bleeding.     

Loss of breast cancer metastasis suppressor 1 protein expression predicts reduced disease-free survival in subsets of breast cancer patients.

PURPOSE: This study aims to determine the effect of loss of breast cancer metastasis suppressor 1 (BRMS1) protein expression on disease-free survival in breast cancer patients stratified by estrogen receptor (ER), progesterone receptor (PR), or HER2 status, and to determine whether loss of BRMS1 protein expression correlated with genomic copy number changes. EXPERIMENTAL DESIGN: A tissue microarray immunohistochemical analysis was done on tumors of 238 newly diagnosed breast cancer patients who underwent surgery at the Cleveland Clinic between January 1, 1995 and December 31, 1996, and a comparison was made with 5-year clinical follow-up data. Genomic copy number changes were determined by array-based comparative genomic hybridization in 47 breast cancer cases from this population and compared with BRMS1 staining. RESULTS: BRMS1 protein expression was lost in nearly 25% of cases. Patients with tumors that were PR negative (P=0.006) or HER2 positive (P=0.039) and <50 years old at diagnosis (P=0.02) were more likely to be BRMS1 negative. No overall correlation between BRMS1 staining and disease-free survival was observed. A significant correlation, however, was seen between loss of BRMS1 protein expression and reduced disease-free survival when stratified by either loss of ER (P=0.008) or PR (P=0.029) or HER2 overexpression (P=0.026). Overall, there was poor correlation between BRMS1 protein staining and copy number status. CONCLUSIONS: These data suggest a mechanistic relationship between BRMS1 expression, hormone receptor status, and HER2 growth factor. BRMS1 staining could potentially be used in patient stratification in conjunction with other prognostic markers. Further, mechanisms other than genomic deletion account for loss of BRMS1 gene expression in breast tumors.