34 resultados para anti-nucleosome

em University of Queensland eSpace - Australia


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The starting point of this thesis was a desire to explain the rapid demise in the popularity which the Communist Party enjoyed in Queensland during the second world war. Wartime Queensland gave the Australian Communist Party its highest state vote and six years later Queensland again gave the Communist Party its highest state vote - this time however, to ban the Party. From this I was led into exploring the changing policies, beliefs and strategies of the Party, as well as the many sub-groups on its periphery, and the shifts in public response to these. In 1939 Townsville elected Australia's first Communist alderman. Five years later, Bowen elected not only Australia's first but also the British Empire's first, Communist state government member. Of the five electorates the Australian Communist Party contested in the 1944 Queensland State elections, in none did the Party's candidate receive less than twenty per-cent of the formal vote. Not only was the Party seemingly enjoying considerable popular support but this was occurring in a State which, but for the Depression years (May 1929 - June 1932) had elected a Labor State Government at every state election since 1915. In the September 1951 Constitution Alteration Referendum, 'Powers To Deal With Communists and Communism', Queensland regist¬ered the nation's highest "Yes" majority - 55.76% of the valid vote. Only two other states registered a majority in favour of the referendum's proposals, Western Australia and Tasmania. As this research was undertaken it became evident that while various trends exhibited at the time, anti-Communism, the work of the Industrial Groups, Labor opportunism, local area feelings, ideological shifts of the Party, tactics of Communist-led unions, etc., were present throughout the entire period, they were best seen when divided into three chronological phases of the Party's history and popularity. The first period covers the consolidation of the Party's post-Depression popularity during the war years as it benefited from the Soviet Union's colossal contribution to the Allied war efforts, and this support continued for some six months or so after the war. Throughout the period Communist strength within the trade union movement greatly increased as did total Party membership. The second period was marked by a rapid series of events starting in March 1946, with Winston Churchill's "Official Opening" of the Cold War by his sweeping attack on Communism and Russia, at Fulton. Several days later the first of a series of long and bitter strikes in Communist-led unions occurred, as the Party mobil¬ized for what it believed would be a series of attacks on the working class from a ruling class, defending a capitalist system on the verge of an economic collapse. It was a period when the Party believed this ruling class was using Labor reformism as a last desperate 'carrot' to get workers to accept their lot within a capitalist economic framework. Out of the Meat Strike emerged the Industrial Groups, who waged not only a determined war against Communist trade union leadership but also encouraged the A.W.U.-influenced State Labor apparatus to even greater anti-Communist antagonisms. The Communist Party's increasing militancy and Labor's resistance to it, ended finally in the collapse of the Chifley Labor government. Characteristically the third period opens with the Communist Party making an another about-face, desperately trying to form an alliance with the Labor Party and curbing its former adventurist industrial policy, as it prepared for Menzies' direct assault. The Communist Party's activities were greatly reduced, a function of both a declining member-ship and, furthermore, a membership reluctant to confront an increasingly hostile society. In examining the changing policies, beliefs and strategies of the Party and the shifts in public response to these, I have tried to distinguish between general trends occurring within Australia and the national party, and trends peculiar to Queensland and the Queensland branch of the Party, The Communist Party suffered a decline in support and membership right across Australia throughout this period as a result of the national policies of the Party, and the changing nature of world politics. There were particular features of this decline that were peculiar to Queensland. I have, however, singled out three features of particular importance throughout the period for a short but more specifically detailed analysis, than would be possible in a purely chronological study: i.e. the Party's structure, the Party's ideological subservience to Moscow, and the general effect upon it of the Cold War.

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Liver suppressor factor one (LSF-1) is a 40-kDa immunosuppressive protein in the serum of rats 60 days after orthotopic liver transplantation (OLT) between the nonrejector combination of DA donors into PVG; recipients. In the present study, the purification of proteins from rat OLT serum taken 60 days after transplantation Mras performed by affinity chromatography using the anti-LSF-1 polyclonal antibody (pAb). The assessment of column eluates using anti-LSF-1 and OLT serum was studied using rat heart and liver transplantation models. Rejection was not suppressed by the administration of OLT serum in heart or liver allografts. However, heart allografts treated with peak eluates (450 mu g single shot im, dissolved in Intralipos) taken from the affinity OLT serum survived significantly longer than untreated rats (median = 36.5 days; n = 7 vs 6.5 days; n = 5, respectively, P = 0.011). The same treatment with anti-LSF-1 column eluates also prolonged liver allografts significantly (>200 days) than those in either the untreated group (median = 11 days; n = 7) or those which received only Intralipos (median = 10.5 days; n = 5, P = 0.019). Subsequent analysis of the N-terminal sequences of some of the proteins which were eluted from the affinity column revealed that the homology of a 30-kDa protein was identical to hemoglobin alpha-chain, a 59-kDa protein to granulocyte inhibitory factor, a 70-kDa and a 90-kDa to albumin and its precursor, respectively. Although the specific immunosuppressive component has not been isolated, our results suggested that the anti-LSF-1 column can extract immunosuppressive moiety of LSF-1 from OLT serum. (C) 1998 Academic Press.

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The use of aspirin as an anti-platelet drug is limited by its propensity to induce gastric injury and by its adverse effect on vascular prostacyclin formation. Two phenolic non-steroidal anti-inflammatory drugs (salicyclic acid and diflunisal) were modified by esterification with a series of O-acyl moieties. The short-term ulcerogenic in vitro and in vivo anti-platelet properties, pharmacodynamic profiles, and extent of hepatic extraction of these phenolic esters were compared with aspirin (acetylsalicylic acid). The more lipophilic esters (longer carbon chain length in O-acyl group) show significantly less gastrotoxicity in stressed rats than does aspirin after a single oral dose. The in vitro and in vivo anti-platelet studies show that these phenolic esters inhibited (1) arachidonate-triggered human platelet aggregation and (2) thrombin-stimulated rat serum thromboxane Ag production by platelets in the clotting process almost as effectively as aspirin. The hepatic extractions of these O-acyl derivatives are significantly higher than those of aspirin. The pharmacodynamic studies show that these O-acyl derivatives of salicylic acid and diflunisal probably bind to, or combine with, the same site on the platelet cyclooxygenase as aspirin. Replacing the O-acetyl group with longer chain O-acyl moiety in this series of phenolic esters markedly reduced the potential of these agents to induce short-term gastric injury but did not lessen their activity as inhibitors of platelet aggregation. These non-acetyl salicylates may therefore represent a novel class of anti-platelet drugs with less ulcerogenic potential.

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Previous studies have demonstrated that 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone (NIH) and several other aroylhydrazone chelators possess anti-neoplastic activity due to their ability to bind intracellular iron. In this study we have examined the structure and properties of NIH and its Fe-III complex in order to obtain further insight into its anti-tumour activity. Two tridentate NIH ligands deprotonate upon coordination to Fe-III in a meridional fashion to form a distorted octahedral, high-spin complex. Solution electrochemistry of [Fe(NIH-H)(2)](+) shows that the trivalent oxidation state is dominant over a wide potential range and that the Fe-II analogue is not a stable form of this complex. The fact that [Fe(NIH-H)(2)](+) cannot-cycle between the Fe-II and Fe-III states suggests that the production of toxic free- radical species, e.g. OH. or O2(.-),is not part of this ligand's cytotoxic action. This suggestion is supported by cell culture experiments demonstrating that the addition of Fe-III to NIH prevents its anti-proliferative effect. The chemistry of this chelator and its Fe-III complex are discussed in the context of understanding its anti-tumour activity.

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It is now well recognized that cervical cancer is caused by infection with certain human papillomavirus (HPV) subtypes and while interferon-alpha (IFN-alpha) is used to treat HPV-infected lesions, HPV appears to have developed a means to avoid the effects of IFN-alpha. Clinically, resistance appears to be associated with the expression of the E7 oncoprotein. Here we investigated the effects of expression in cells of the E7 protein from high- and low-risk papillomavirus subtypes on a range of responses to IFN-alpha. 2fTGH, a cell line dependent on IFN-alpha for growth in selection medium, grew significantly less well in the presence of E7, and the antiproliferative effects of IFN-alpha upon epithelial cells was lost upon E7 expression. The antiviral effects of IFN-alpha were abrogated in E7-expressing cells. Loss of response to IFN-alpha was found to occur in both high- and low-risk papillomaviruses. Finally, deletion of amino acids 21-24 of HPV type 16 E7 protein partially reversed repression. We conclude that E7 inhibits the functional effects of IFN-alpha and that this property is shared by all HPV subtypes tested. (C) 2000 Academic Press.

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IL-12 has been demonstrated to have potent anti-tumor activities in a variety of mouse tumor models, but the relative roles of NK, NKT, and T cells and their effector mechanisms in these responses have not been fully addressed. Using a spectrum of gene-targeted or Ab-treated mice we have shown that for any particular tumor model the effector mechanisms downstream of IL-12 often mimic the natural immune response to that tumor. For example, metastasis of the MHC class I-deficient lymphoma, EL4-S3, was strictly controlled by NK cells using perforin either naturally or following therapy with high-dose IL-12. Intriguingly, in B16F10 and RM-1 tumor models both NK and NKT cells contribute to natural protection from tumor metastasis, In these models, a lower dose of IL-12 or delayed administration of IL-12 dictated a greater relative role of NKT cells in immune protection from tumor metastasis. Overall, both NK and NKT cells can contribute to natural and IL-12-induced immunity against tumors, and the relative role of each population is turner and therapy dependent.

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This paper presents observations of summertime anti-winds monitored under ideal conditions in the Lake Tekapo hydro-catchment situated in the central Southern Alps, New Zealand. Onset and cessation of anti-winds was observed to coincide with the change in phase of the surface limbs of thermally generated valley and mountain winds under settled anti-cyclonic conditions. Anti-winds were best developed in the early morning before surface heating and associated convective mixing of the valley atmosphere began to mask the boundaries between the surface based limb of the mountain-valley wind and the corresponding anti-wind. By mid-day, the anti-valley wind exceeded the height of the surrounding ridgeline and became embedded in the topographically channeled gradient wind. Observations presented here have both theoretical and applied implications with regard to the development of thermally generated wind systems in deep alpine valleys, and their role in the dispersion of air pollution.

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TNF-alpha neutralising agents such as Infliximab (Remicade(R)), Etanercept (Enbrel(R)) and the IL-1 receptor antagonist Anakinra (Kineret(R)), are currently used clinically for the treatment of many inflammatory diseases such as Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriatic arthritis and psoriasis. These protein preparations are expensive to manufacture and administer, need to be injected and can cause allergic reactions. An alternative approach to lowering the levels of TNF-alpha and IL-1 beta in inflammatory disease, is to inhibit the enzymes that generate these cytokines using cheaper small molecules. This paper is a broad overview of the progress that has been achieved so far, with respect to small molecule inhibitor design and pharmacological studies (in animals and humans), for the metalloprotease Tumour Necrosis Factor-alpha Converting Enzyme (TACE) and the cysteine protease Caspase-1 (Interieukin-1 beta Converting Enzyme, ICE). Inhibitors of these two enzymes are currently considered to be good therapeutic targets that have the potential to provide relatively inexpensive and orally bioavailable anti-inflammatory agents in the future.

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This study investigated the effect of two anti-pronation taping techniques on vertical navicular height, an indicator of foot pronation, after its application and 20 min of exercise. The taping techniques were: the low dye (LD) and low dye with the addition of calcaneal slings and reverse sixes (LDCR). A repeated measures study was used. It found that LDCR was superior to LD and control immediately after application and exercise. LD was better than control immediately after application but not after exercise. These findings provide practical directions to clinicians regularly using anti-pronation taping techniques.

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Various members of the bZip and bHLH-Zip families of eukaryotic transcription factors, including Jun, Fos, and Myc, have been identified as oncoproteins; mutation or deregulated expression of these proteins leads to certain types of cancer. These proteins can only bind to their cognate DNA enhancer sites following homodimerization, or heterodimerization with another family member, via their leucine zipper domain. Thus, a novel anticancer strategy would be to inhibit dimerization of these proteins, thereby blocking their DNA binding and transactivation functions. In this paper we show that it is possible to rationally design leucine zipper peptides that bind with high affinity to the leucine zipper dimerization domains of c-Jun and c-Fos, thus preventing the formation of functional c-Jun homodimers and c-Jun:c-Fos heterodimers; we refer to such peptides as superzippers (SZs). In vivo, c-Jun:SZ and c-Fos:SZ heterodimers should be nonfunctional as they lack one of the two basic domains that are essential for DNA binding. While the transport of a peptidic agent into cells often poses a severe obstacle to its therapeutic use, we show that a 46-residue leucine zipper peptide can be transported into HeLa cells by coupling it to a 17-residue carrier peptide from the Antennapedia homeodomain, thus paving the way for detailed studies of the therapeutic potential of superzipper peptides.

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