Peter Marcus Kristensen

Plasminogen Activators, Tissue Degradation, and Cancer

Publisher Summary This chapter discusses the role of plasminogen activators in various biological processes. In specific, it describes two types of plasminogen activators—namely, the urokinase-type plasminogen activator (u-PA) and the tissue-type plasminogen activator (t-PA), which are essentially different gene products. The amino acid sequences of these activators and nucleotide sequences of the corresponding cDNAs have largely been determined, and the cDNAs have been cloned using recombinant techniques. A variety of enzymatic as well as immunological assay and detection methods have also been developed that allows a precise quantification of the activators, a distinction between u-PA and t-PA, determination of whether an activator is present in its active or zymogen form, analysis of the kinetics of different steps of the cascade reaction, and immunocytochemical identification of u-PA and t-PA in tissue sections. Much of the studies on plasminogen activators and cancer has been guided by the hypothesis that proteolysis of the components of extracellular matrix, initiated by the release of plasminogen activator from the cancer cells, plays a decisive role for the degradation of normal tissue, and thereby for invasive growth and metastases.

Human endothelial cells contain one type of plasminogen activator

At least two types of animal plasminogen activating enzymes exist, differing in amino acid sequence, molecular mass and immunological reactivity: the urokinase‐type and the tissue‐type plasminogen activators. By affinity chromatography with monoclonal antibodies, we have purified the human activators of both types to homogeneity. Using immunocytochemistry with rabbit antibodies raised against these preparations, we now demonstrate that the plasminogen activator present in endothelium of veins and other blood vessels is of the tissue‐type. No urokinase‐type plasminogen activator immunoreactivity was detected in endothelial cells in the intact organism. These findings support the assumption that mobilization of plasmin for different purposes may involve different types of plasminogen activators, and that the plasminogen activator involved in thrombolysis is of the tissue‐type.

Gonadotropin regulation of tissue-type and urokinase-type plasminogen activators in rat granulosa and theca-interstitial cells during the periovulatory period

Plasminogen activators (PAs) are believed to be involved in ovulation. Because both tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) are secreted by cultured rat granulosa cells, we have examined the activities of these proteins in ovarian homogenates as well as granulosa and theca-interstitial (TI) cells during gonadotropin-induced ovulation. Immature rats were injected with 20 IU pregnant mare serum gonadotropin (PMSG) to initiate follicle development, followed by treatment with 10 IU hCG 48 h later to induce ovulation. Ovarian proteins were separated by SDS-PAGE and PA activity determined by fibrin overlay. The activity of tPA, but not uPA, was stimulated following PMSG treatment in ovarian homogenates. Subsequent hCG injection further increased the tPA activity in a time-dependent manner, reaching a maximum (12 h after hCG treatment) immediately prior to ovulation and declined thereafter. Similar preovulatory increases in tPA activity were detected in isolated granulosa cells. Although both tPA and uPA activities were increased in TI cells after PMSG administration, no further increases were detected after hCG treatment. To estimate enzyme secretion, ovarian cells obtained at various preovulatory periods were incubated for 24 h in vitro. The ability of granulosa cells to secrete tPA, but not uPA, increased following in vivo PMSG and hCG treatment in a time-dependent manner, reaching a maximum immediately prior to ovulation. During the preovulatory period, an abrupt increase in tPA secretion by TI cells was also detected. Using immunohistochemical staining for tPA, it was found that ovarian sections from preovulatory rats at 12 h after hCG injection stained positively in granulosa, theca interna, and interstitial gland cells.(ABSTRACT TRUNCATED AT 250 WORDS)

The elephant in the room: mapping the latent communication pattern in European Union studies

European Union (EU) studies is known as a fragmented and interdisciplinary field. Drawing on bibliometric methods, this article presents a novel approach to examining the alleged lines of fragmentation in EU studies. It maps the network structure arising from the citation practices in journals concerned with EU studies by analysing 2,561 documents, containing 66,162 references, published in four authoritative EU journals in the period 2003–2010. The article finds: (1) a complex network of EU and non-EU sources clustering around different bordering disciplines, particularly Political Science, Comparative Politics, International Relations and Public Administration; (2) that the two core journals – Journal of European Public Policy and Journal of Common Market Studies – play an integrating function by holding the various subfields of EU studies together; and (3) a transatlantic divide in communication practices of EU scholars.

Localization of urokinase-type plasminogen activator receptor on U937 cells: Phorbol ester PMA induces heterogeneity☆

The binding of human urokinase-type plasminogen activator (u-PA) to the surface of the human monocytic cell line U937 was studied by immunological detection of bound u-PA or binding of biotinylated diisopropyl fluorophosphate-inactivated human u-PA visualized by light or electron microscopy. Untreated U937 cells showed a characteristic binding pattern, with the majority of the u-PA bound to the microvillar-containing protruding pole of the cells. After treatment with the phorbol ester PMA, the resulting adherent cell population was very heterogeneous with respect to both cellular morphology and u-PA binding. The bound u-PA was distributed on both the dorsal and the substrate side of the cells, and the patches of bound u-PA could not be correlated to any typical membrane conformations or cell-cell or cell-substratum contacts. When a monoclonal antibody directed against the amino-terminal fragment (ATF) of u-PA was used, the results were identical regardless of whether intact u-PA or ATF was used for binding to the cells. In contrast, when a monoclonal antibody recognizing the non-receptor-binding protease domain of u-PA was used, bound ATF showed no staining, while bound intact u-PA was stained as efficiently as above. The alteration of u-PA receptor distribution following treatment with PMA could be related to the changes in glycosylation and ligand affinity of the purified u-PA receptor previously described following PMA treatment of U937 cells.

Discipline admonished: On International Relations fragmentation and the disciplinary politics of stocktaking

The International Relations discipline has recently witnessed a wave of stocktakings and they surprisingly often follow the narrative that the discipline once revolved around all-encompassing great debates, which, either neatly or claustrophobically depending on the stocktaker, organized the discipline. Today, most stocktakers argue, International Relations has moved beyond great debate — the very symbol of the discipline — and is undergoing fragmentation. For some scholars, fragmentation is caused by the lack of any great structuring debate and a proliferation of less-than-great theories. To others, fragmentation is a result of the divisive great debates themselves. When stocktakers portray fragmentation as novelty, however, they neglect the prominent historical record of this fragmentation narrative. By rereading stocktaking exercises from the 1940s to today, this article argues that the stocktaking genre — past and present — is conducive to seeing the past as more simple, coherent and ordered while the present is marked by fragmentation and cacophony. Neat summaries of the academic scene in one’s own time are quite rare. Few stocktakers ever identified one conversation/debate driving the discipline, not during the first, second, third or fourth debates — and those who did disagreed on what the main trenches and its warriors were. The article concludes by arguing that International Relations’ recurrent anxieties about its fragmentation beg questions, not about whether it is real this time, but about the disciplinary politics of this stocktaking narrative. Stocktaking exercises are never only objective descriptions of a current state of disarray; they are political moves in the discipline. Dissatisfied scholars employ this narrative to lead the discipline in certain directions, often quite idiosyncratic ones that reflect and serve their own position in International Relations.

How can emerging powers speak? On theorists, native informants and quasi-officials in International Relations discourse

Emerging powers like China, India and Brazil are receiving growing attention as objects in International Relations (IR) discourse. Scholars from these emerging powers are rarely present as subjects in mainstream IR discourse, however. This paper interrogates the conditions for scholars in emerging powers to speak back to the mainstream discipline. It argues, first, that ‘theory speak’ is rare from scholars based in periphery countries perceived to be ‘emerging powers’. Despite increasing efforts to create a ‘home-grown’ theoretical discourse in China, India and Brazil, few articles in mainstream journals present novel theoretical frameworks or arguments framed as non-Western/Southern theory or even as a ‘Chinese school’ or ‘Brazilian concepts’. Second, scholars from emerging powers tend to speak as ‘native informants’ about their own country, not about general aspects of ‘the international’. Third, some scholars even speak as ‘quasi-officials’, that is, they speak for their country.

International relations in China and Europe: the case for interregional dialogue in a hegemonic discipline

Abstract The international relations (IR) discipline is known as an ‘American Social Science’ dominated by scholars and theories from the US core. This paper compares IR in two noncore settings, China and Europe. It shows that there is a growing institutional and intellectual integration into global Anglophone, mostly American, IR in both Europe and China. Both Chinese and European IR communities have established top Anglophone journals like the European Journal of International Relations and the Chinese Journal of International Politics to spearhead their integration into mainstream Anglophone IR and carve out a space for regional thinking. Yet, the analysis of their publication and citation patterns shows that IR outside the American core communicates through a hub-and-spokes system where there is always a connection to the American core but rarely very strong linkages to other peripheral regions. The two journals studied thus function as outlets for ‘local’ and American scholars, rely on ‘local’ and American sources, and there is very little integration and exchange between Chinese and European IR. Chinese and European IR would benefit from such a dialogue, especially regarding ‘schools’ of IR at the margins of an ‘American social science’.

Conclusions: Wor(l)ds Beyond the West

Globalizing International Relations sets out to critically examine divides and diversity in the discipline, both within and beyond its ‘Western’ core. It is an important contribution to the sociology of the International Relations (IR) discipline by both contributing to the longstanding literature on the parochialism of the mainstream American IR discipline (Hoffmann 1977; Holsti 1985; Waever 1998; Smith 2000; Crawford and Jarvis 2001) and its colonial legacies (Long and Schmidt 2005), as well as to the increasing number of inquiries into how IR is done, sometimes differently, elsewhere around the world (Jorgensen and Knudsen 2006; Tickner and Waever 2009; Acharya and Buzan 2010). The mostly empirical approach taken throughout the chapters does not stand so much in contrast to, or move beyond, these earlier postcard-like studies of IR in different locations around the world, but inscribes itself as the necessary extension of these. The previous mappings of what IR is and how it is done in China, Russia, Iran or Latin America are a necessary background for the endeavor undertaken here. As the editors have summarized and tabularized the chapters in the introduction, I wish to use this concluding chapter to position the volume in relation to existing research in the sociology of IR and discuss how it contributes to that literature.