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Biomedical subjects

M Kasten

Publications and source records attributed to M Kasten.

24 records · Page 2Linked to original sources
PubMed1987

Interference of cartilage surface with interaction of granulocyte elastase with alpha 1-proteinase inhibitor. An in vitro model of enzyme inhibition in the joint space.

Synovial fluids of patients suffering from rheumatoid arthritis contain elevated levels of granulocyte (PMN) elastase in complex with alpha 1-proteinase inhibitor (alpha 1-PI), whereas free-elastase activity is usually not detectable. This absence of free enzymatic activity in joint effusions has cast some doubt on the pathophysiological relevance of PMN elastase in inflammatory joint destruction. Our in vitro experiments using bovine nasal cartilage demonstrate that incubation with elastase and alpha 1-PI in equimolar concentrations to or even in excess of the serum proteinase inhibitor resulted in significant tissue destruction as assessed by histological staining for proteoglycans, release of uronic acid from the matrix and loss of mechanical stability. Though in the supernatants containing alpha 1-PI, free-elastase activity was not detectable, immunofluorescent staining for elastase evidenced penetration of the enzyme into the matrix. Simultaneous measurements of the incubation media employing a sandwich enzyme-linked immunoadsorption assay (ELISA) revealed PMN elastase in complex with alpha 1-PI but without correlation to the parameters of tissue degradation. In comparison with the results obtained using the chromogenic substrate Suc-Ala-Ala-Ala-pNA (SAPA) for titration of alpha 1-PI against elastase, the employment of cartilage matrix showed that a fourfold increase in inhibitor concentration was necessary to achieve 100% enzyme inhibition. Hence, cartilage surface obviously interferes with the interaction between alpha 1-PI and elastase. Measurements of elastase-inhibitor concentrations or free enzymatic activity in synovial fluid seem to have limited value in predicting cartilage destruction.

Animals↗
PubMedDate not supplied

Cell cycle and apoptosis.

In multicellular organisms, cell proliferation and death must be regulated to maintain tissue homeostasis. Many observations suggest that this regulation may be achieved, in part, by coupling the process of cell cycle progression and programmed cell death by using and controlling a shared set of factors. An argument in favor of a link between the cell cycle and apoptosis arises from the accumulated evidence that manipulation of the cell cycle may either prevent or induce an apoptotic response. This linkage has been recognized for tumor suppressor genes such as p53 and RB, the dominant oncogene, c-Myc, and several cyclin-dependent kinases (Cdks) and their regulators. These proteins that function in proliferative pathways may also act to sensitize cells to apoptosis. Indeed, unregulated cell proliferation can result in pathologic conditions including neoplasias if it is not countered by the appropriate cell death. Translating the knowledge gained by studying the connection between cell death and cell proliferation may aid in identifying novel therapies to circumvent disease progression or improve clinical outcome.

Animals↗
PubMedDate not supplied

Current understanding of AIDS pathogenesis.

From the mid 1990s, considerable progress has been achieved in understanding the biology of the human immunodeficiency virus type 1 (HIV-1), and the pathogenesis of the acquired immunodeficiency syndrome (AIDS). However, these achievements are still not sufficient to indicate the reasons for failure of the host immune response in suppressing HIV-1 infection and why the immune system collapses at the end of the clinical latency period, followed by progression to the terminal course of the disease. A more complete view of the dynamics of AIDS pathogenesis may greatly facilitate the development of novel and ambitious therapeutic interventions, that are needed to counteract the onset of HIV-1 variants resistant to current antiretroviral treatments, to ensure affordable therapy programs for developing countries, and, in the long term, to eradicate the virus from patients and to confer protective immunity to HIV-1 infection.

HIV Infections↗