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Biomedical subjects

M Hemmes

Publications and source records attributed to M Hemmes.

At least 19 recordsLinked to original sources
PubMed1999

Novel path to activation of vascular smooth muscle cells: up-regulation of gp130 creates an autocrine activation loop by IL-6 and its soluble receptor.

This study describes a novel path to the activation of smooth muscle cells (SMC) by the IL-6/soluble IL-6 receptor (sIL-6R) system. Human vascular SMC constitutively express only scant amounts of IL-6R and so do not respond to stimulation with this cytokine. We show that SMC also do not constitutively express appreciable levels of gp130, which would render them sensitive to transsignaling by the IL-6/sIL-6R complex. Because gp130 is generally believed not to be subject to regulation, SMC would thus appear not to qualify as targets for the IL-6/sIL-6R system. However, we report that treatment of SMC with IL-6/sIL-6R provokes marked up-regulation of gp130 mRNA and surface protein expression. This is accompanied by secretion of IL-6 by the cells, so that an autocrine stimulation loop is created. In the wake of this self-sustaining system, there is a selective induction and secretion of MCP-1, up-regulation of ICAM-1, and marked cell proliferation. The study identifies SMC as the first example of cells in which gp130 expression is subject to substantive up-regulation, and discovers a novel amplification loop involving IL-6 and its soluble receptor that drives SMC into a proinflammatory state.

Aged↗
PubMed1999

Complement and atherogenesis: binding of CRP to degraded, nonoxidized LDL enhances complement activation.

Complement activation occurs in temporal correlation with the subendothelial deposition of LDL during early atherogenesis, and complement also plays a pathogenetic role in promoting lesion progression. Two lesion components have been identified that may be responsible for complement activation. First, enzymatic degradation of LDL generates a derivative that can spontaneously activate complement, and enzymatically degraded LDL (E-LDL) has been detected in the lesions. Second, C-reactive protein (CRP) colocalizes with complement C5b-9, as evidenced by immunohistological studies of early atherosclerotic lesions, so the possibility exists that this acute phase protein also fulfills a complement-activating function. Here, we report that addition of LDL and CRP to human serum did not result in significant C3 turnover. Addition of E-LDL provoked complement activation, which was markedly enhanced by CRP. Binding of CRP to E-LDL was demonstrated by sucrose flotation experiments. Binding was Ca(2+)-dependent and inhibitable by phosphorylcholine, and the complement-activating property of E-LDL was destroyed by treatment with phospholipase C. These results indicated that CRP binds to phosphorylcholine groups that become exposed in enzymatically degraded LDL particles. Immunohistological studies complemented these findings in showing that CRP colocalizes with E-LDL in early human atherosclerotic lesions. Thus enzymatic, nonoxidative modification of tissue-deposited LDL can be expected to confer CRP-binding capacity onto the molecule. The ensuing enhancement of complement activation may be relevant to the development and progression of the atherosclerotic lesion.

C-Reactive Protein↗
PubMed1999

Enzymatically modified, nonoxidized LDL induces selective adhesion and transmigration of monocytes and T-lymphocytes through human endothelial cell monolayers.

Circulating monocytes and T lymphocytes extravasate through the endothelium at sites of developing atheromatous lesions, where they tend to accumulate and mediate the progression of the disease. We have previously demonstrated the presence of an enzymatically degraded, nonoxidized form of LDL (E-LDL) in early human fatty streaks, which possesses major biological properties of an atherogenic lipoprotein. The effects of E-LDL on human endothelial cells have now been studied with respect to adhesion and transmigration of monocytes and T lymphocytes. E-LDL induced a rapid and dose-dependent selective adhesion of monocytes and T lymphocytes to endothelial cell monolayers within 30 minutes of incubation. Maximal increases in the number of adherent monocytes (8-fold) and of adherent T lymphocytes (4-fold) were observed after treatment with 50 microg/mL E-LDL. E-LDL was more active than oxidized LDL (ox-LDL), whereas native LDL produced only minor adhesive effects. Both E-LDL and ox-LDL enhanced transmigration of monocytes and of T lymphocytes through endothelial monolayers. Again, E-LDL was more potent than ox-LDL, inducing transmigration to a similar extent as N-formyl-Met-Leu-Phe. In endothelial cells, E-LDL stimulated upregulation of intercellular adhesion molecule-1 (ICAM-1), platelet-endothelial cells adhesion molecule-1 (PECAM-1), P-selectin, and E-selectin with distinct kinetics. Analyses with blocking antibodies indicated that ICAM-1 and P-selectin together mediated approximately 70% of cell adhesion, whereas blocking of PECAM-1 had no effect on adhesion but reduced transmigration to less than 50% of controls. E-LDL also upregulated expression of ICAM-1 in human aortic smooth muscle cells, and this correlated with increased adhesion of T lymphocytes. E-LDL is thus able to promote the selective adhesion of monocytes and T lymphocytes to the endothelium, stimulate transmigration of these cells, and foster their retention in the vessel wall by increasing their adherence to smooth muscle cells. These findings underline the potential significance of E-LDL in the pathogenesis of atherosclerosis.

Arteriosclerosis↗
PubMed1995

The Vista Awards. New facilities for a new age.

To build an outstanding health care facility, you need to start with an outstanding project team. That's the premise underlying the first Vista Awards. A look at the winning projects and teams.

Architecture↗
PubMed1993

Health care construction in the 1990s.

Need proof that health care construction is booming? Just look at the model (below) of Northwestern Memorial Hospital's $580 million replacement facility, to be built in the heart of Chicago.

Academic Medical Centers↗
PubMed1993

DuPont/HFM Forum on carpet in health care facilities. Roundtable discussion.

DuPont and Health Facilities Management magazine invited 20 national experts to Dalton, GA--the carpet-manufacturing capital of the world--on May 13 to take part in DuPont's first-ever Forum on Carpet in Health Care Facilities. During the two-hour roundtable discussion, moderated by DuPont's C. Jack Murph and HFM's Michael Hemmes, end-users, interior designers and mill representatives talked about the aesthetic, economic and performance aspects of using carpet in health care settings. Here's an edited version of what they said.

Color↗