BACKGROUND: Breast tumors contain high numbers of infiltrating macrophages. The role and function of these cells within the tumor remain unclear, but a number of studies have found an association between poor prognosis and macrophage content in human breast cancer. Both hypoxia and TGFbeta-1 have been shown to regulate VEGF in other cell types. We hypothesized that breast tumor-associated macrophages produce VEGF and that macrophage production of this factor is regulated by both hypoxia and TGFbeta-1. METHODS: Paraffin-embedded breast tumor sections were stained immunohistochemically with anti-VEGF, anti-CD68, and anti-cytokeratin. Monocytes were matured for 3 days in 20% autologous plasma and activated with 1000 U/mL interferon-gamma for 24 hours. Supernatants were assayed for VEGF protein by ELISA. Total RNA was isolated from cells and reverse transcribed to cDNA, which was used as a template in PCR reactions for VEGF and beta-actin. RESULTS: Both tumor cells and tumor macrophages produce VEGF in human breast tumors. Hypoxia increases VEGF protein and mRNA levels in monocyte-derived macrophages, whereas TGFbeta-1 increases VEGF protein but not mRNA under hypoxic growth conditions. CONCLUSIONS: Breast tumor-associated macrophages may contribute to the angiogenic activity of human breast tumors by producing VEGF. Macrophage production of VEGF is upregulated by hypoxia and TGFbeta-1, both of which occur in the tumor environment. Macrophage production of VEGF is regulated at both the mRNA and protein levels.

Breast Neoplasms↗

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Colocalisation of human immunodeficiency virus and human cytomegalovirus infection in brain autopsy tissue from AIDS patients.

We have examined 26 human AIDS brains obtained at post mortem for infection by human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV), and for dual infection of cells by both viruses. The techniques used were enzyme-linked immunocytochemistry for HCMV and in situ hybridisation using a cDNA probe for HIV. Using these techniques, HCMV infection was detected in 14 brains, HIV infection in 14 brains, and coinfection with HIV and HCMV in 7 brains. Four case of dual HIV/HCMV infection were found where no colocalisation could be detected. In randomly chosen dually infected areas 19.2% of infected cells were coinfected with both viruses. Although cells identified morphologically as macrophages were the most common infected cell type, astrocytes and neurons were both singly and doubly infected with HIV and HCMV. Complete clinical data were available for 4 of the 7 cases with coinfection and each had AIDS dementia complex.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

The role of apoptotic cell death in cardiovascular disease.

BACKGROUND: Programmed cell death, or apoptosis, is a distinct, managed form of cell death. It is fundamentally different from necrosis. It is a genetically controlled, energy-dependent method of cellular deletion without inflammation. In the cardiovascular system, apoptosis occurs as a primary and secondary event in disease pathogenesis. This review addresses our current understanding of the initiation, propagation and significance of apoptosis in the cardiovascular system, as well as assessing therapeutic potentials arising therefrom. METHODS: A Medline search was performed and relevant publications reviewed. Further articles were obtained from the references of these publications. RESULTS: and conclusions Apoptotic cell death is a key element in the pathogenesis and progression of ischaemia-reperfusion (IR) injury, cardiac failure, myocardial infarction, atherosclerosis, endothelial dysfunction and the clinical syndromes which these situations produce. Our increased understanding of the role of apoptosis in the pathogenesis of cardiovascular disease offers potential to develop new therapeutic strategies.

Apoptosis↗

PubMedDate not supplied

Decision analysis for lower-third-molar surgery.

The objective of the study was to identify those factors that should affect treatment planning for patients who have lower third molars, using decision-analytic techniques. Utility values based on data from 104 patients indicated that the respondents considered that postoperative complications (except mild pain and temporary paresthesia) reduced health to a greater degree than did complications following non-intervention. A decision analysis indicated that the maximum expected utility of prophylactic third-molar surgery (60.25) was lower than that for non-intervention (76.96). The decision was sensitive to changes in the probabilities of occurrence of recurrent pericoronitis (threshold = 0.52), resorption of an adjacent tooth (threshold = 0.29), loss of an adjacent tooth (threshold = 0.32), and cystic change (threshold = 0.34). These thresholds are much higher than the incidence of problems affecting the lower third molar shown by a concurrent clinical audit and literature review. This study therefore suggests that lower third molars should not be removed prophylactically.

Decision Trees↗

PubMedDate not supplied

Community initiatives. Accidents will happen.

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Accident Prevention↗