A PHARMACOLOGICAL EVALUATION OF THE MECHANISM OF CYTOTOXICITY OF 9-BETA-D- XYLOFURANOSYLADENINE IN CHINESE HAMSTER OVARY CELLS

The biochemical determinants of cytotoxicity of the purine nucleoside analog, 9-(beta)-D-xylofuranosyladenine (xyl-A) were studied in wild-type Chinese hamster ovary cells and in nucleoside kinase deficient mutants. It was found that {('3)H}xyl-A was readily phosphorylated to the triphosphate level in both the wild-type and deoxycytidine kinase deficient mutant, but not by the adenosine kinase deficient cells. Values for the apparent Km and Vmax of this uptake process were 43.9 (mu)M and 118.7 nmol/min/10('9) cells, respectively. Cloning procedures indicated that the viability of CHO cells was decreased 90 per cent by a 5-hr incubation with 10 (mu)M xyl-A. However, the toxicity of xyl-A was increased 100-fold by the addition of a nontoxic concentration (10 (mu)M) of the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) to the medium. High-pressure liquid chromatographic analysis indicated that after 5 hr, the concentration of 9-(beta)-D-xylofuranosyladenine 5'-triphosphate (xyl-ATP) in cells incubated with xyl-A plus EHNA was 2.0 mM, four times greater than in those cells incubated with xyl-A alone. Incubation with xyl-A plus EHNA had no significant effect on the cellular concentrations of 5-phosphoribosyl-1-pyrophosphate after 1 hr whereas, treatment with 3'-dexoyadenosine (cordycepin) decreased the concentration of this metabolite. Determinations of the cellular nucleoside triphosphates indicated that under conditions that resulted in an intracellular accumulation of 500 (mu)M xyl-ATP, the endogenous concentrations of neither the ribonucleoside triphosphates nor deoxyribonucleoside triphosphates were significantly different from those of control cells. The ID(,50) for {('3)H}thymidine incorporation into DNA, 105 (mu)M xyl-ATP, was four-fold less than the ID(,50) for {('3)H}uridine incorporation into RNA suggesting that the process of DNA synthesis is more sensitive to the presence of xyl-ATP. When removed from exogenous xyl-A, CHO cells failed to recover their ability to synthesize RNA and DNA, although the intracellular xyl-ATP concentration decreased to less than 35 (mu)M. The selective inhibition of RNA synthesis by 6-azauridine did not prevent the expression of toxicity by xyl-ATP. However, the selective inhibition of DNA synthesis by ara-C significantly spared toxicity in cells that had accumulated an otherwise lethal concentration of xyl-ATP. It is shown that in cells which had accumulated 1.27 mM {('3)H}xyl-ATP, {('3)H}xyl-A was found to terminate cellular RNA chains at a frequency of 1.42 (mu)mol of {('3)H}xyl-A 3' termini per mol of mononucleotide. These results indicate that a general mechanism for the toxicity of xyl-A to CHO cells includes the cellular accumulation of xyl-ATP, which serves as a substrate for RNA synthesizing enzymes and subsequently is incorporated into nascent RNA transcripts as a chain terminator. A specific mechanism involving the premature termination of RNA primers required for the initiation of DNA synthesis is proposed to account for the inhibitory action of xyl-ATP on DNA synthesis. ^

Globalized Antiquity: Uses and Perceptions of the Past in South Asia, Mesoamerica, and Europe

„Antike“ ist keine europäische Exklusivität: Das Buch zeigt, wie in Südasien, Mesoamerika und Europa je eigene Antiken konstruiert werden. In den untersuchten vorkolonialen, kolonialen und postkolonialen Zusammenhängen wird die Antike durch die zeitgenössische Geschichtspolitik stark mitbestimmt. Der Vergleich lässt die Verflechtung der Vorstellungen über die Vergangenheit zwischen „klassischer“ europäischer, indischer und mesoamerikanischer Antike von der frühen Neuzeit bis in die Gegenwart erkennen. Das Buch bietet Denkanstöße für Personen, die sich mit historisch interessierter Kulturanthropologie, kritischer Altertumswissenschaft und Globalgeschichte beschäftigen.

The 1452 or 1453 A.D. Kuwae Eruption Signal Derived from Multiple Ice Core Records: Greatest Volcanic Sulfate Event of the Past 700 Years

We combined 33 ice core records, 13 from the Northern Hemisphere and 20 from the Southern Hemisphere, to determine the timing and magnitude of the great Kuwae eruption in the mid-15th century. We extracted volcanic deposition signals by applying a high-pass loess filter to the time series and examining peaks that exceed twice the 31 year running median absolute deviation. By accounting for the dating uncertainties associated with each record, these ice core records together reveal a large volcanogenic acid deposition event during 1453 - 1457 A. D. The results suggest only one major stratospheric injection from the Kuwae eruption and confirm previous findings that the Kuwae eruption took place in late 1452 or early 1453, which may serve as a reference to evaluate and improve the dating of ice core records. The average total sulfate deposition from the Kuwae eruption was 93 kg SO4/km(2) in Antarctica and 25 kg SO4/km(2) in Greenland. The deposition in Greenland was probably underestimated since it was the average value of only two northern Greenland sites with very low accumulation rates. After taking the spatial variation into consideration, the average Kuwae deposition in Greenland was estimated to be 45 kg SO4/km(2). By applying the same technique to the other major eruptions of the past 700 years our result suggests that the Kuwae eruption was the largest stratospheric sulfate event of that period, probably surpassing the total sulfate deposition of the Tambora eruption of 1815, which produced 59 kg SO4/km(2) in Antarctica and 50 kg SO4/km(2) in Greenland.

Transgressive sporting bodies - A theoretical and critical dicourse analysis of the representation of Caster Semenya in Swiss print media

A debate about Caster Semenya's female sex began shortly after the South African runner won gold in the women’s 800m final at the 2009 Athletic World Championships held in Berlin. Her victory was disputed through questions about her right to compete as a ‘woman’, with the International Association of Athletics Federation (IAAF) announcing she would be required to undergo a gender verification test before her victory could be confirmed. Using the theoretical frame of social constructionism (Berger & Luckmann), poststructuralism (Foucault), gender- and postcolonial theories (Butler; Hall; Spivak) and the methodology of critical discourse analysis (Jaeger), the paper explores the way the possible intersexuality of Caster Semenya was contextualised in mainstream Swiss German-language print media. The analyses will firstly look at the way in which Caster Semenya was constructed as a ʻfallen hero’ and stigmatised as a double-dealer and unacceptable deviant body. The rumours amongst athletes and commentators became news in the media, which focused on descriptions of her habitus, her muscular body and her deep voice. Through theoretical discussion the paper argues that the media response to Caster Semenya exemplifies Butler’s claim that the discursive framework of gender constructs and naturalises sex. A key question is therefore whether the designation of deviant bodies to a ʻfield of deformation’ (Butler) works to pluralise the field of gender, or rather, as Butler suggests, it tends that those bodies might call into questions. The final part of the paper discusses how gender, ethnicity and sexuality combine to constitute the black female sporting body as a spectacle of otherness. It is evident that this otherness is made manifest through the function of those bodies as a site of transgression, as the boundary between male and female, and often as the boundary between culture and nature (Hall). Using the example of the controversy surrounding Caster Semenya, this paper aims to demonstrate how the post/colonial white female body is reproduced by western norms of gender, sexuality, beauty and sporting behaviour, in the sense of a feminine sporting genderperformance. The media controversy will be also read through the lens of the globalisation of certain ideas of normative bodies, sex, ethnicity and gender and the challenge of changing stereotypes through transgression. Keywords: gender- and postcolonial theories, discourse analysis, print media, Caster Semen-ya, deviant body, ethnicity, intersexuality

Transgressive sporting bodies - A theoretical and critical dicourse analysis of the representation of Caster Semenya in Swiss print media

A debate about Caster Semenya's female sex began shortly after the South African runner won gold in the women’s 800m final at the 2009 Athletic World Championships held in Berlin. Her victory was disputed through questions about her right to compete as a ‘woman’, with the International Association of Athletics Federation (IAAF) announcing she would be required to undergo a gender verification test before her victory could be confirmed. Using the theoretical frame of social constructionism (Berger & Luckmann), poststructuralism (Foucault), gender- and postcolonial theories (Butler; Hall; Spivak) and the methodology of critical discourse analysis (Jaeger), the paper explores the way the possible intersexuality of Caster Semenya was contextualised in mainstream Swiss German-language print media. The analyses will firstly look at the way in which Caster Semenya was constructed as a ʻfallen hero’ and stigmatised as a double-dealer and unacceptable deviant body. The rumours amongst athletes and commentators became news in the media, which focused on descriptions of her habitus, her muscular body and her deep voice. Through theoretical discussion the paper argues that the media response to Caster Semenya exemplifies Butler’s claim that the discursive framework of gender constructs and naturalises sex. A key question is therefore whether the designation of deviant bodies to a ʻfield of deformation’ (Butler) works to pluralise the field of gender, or rather, as Butler suggests, it tends that those bodies might call into questions. The final part of the paper discusses how gender, ethnicity and sexuality combine to constitute the black female sporting body as a spectacle of otherness. It is evident that this otherness is made manifest through the function of those bodies as a site of transgression, as the boundary between male and female, and often as the boundary between culture and nature (Hall). Using the example of the controversy surrounding Caster Semenya, this paper aims to demonstrate how the post/colonial white female body is reproduced by western norms of gender, sexuality, beauty and sporting behaviour, in the sense of a feminine sporting genderperformance. The media controversy will be also read through the lens of the globalisation of certain ideas of normative bodies, sex, ethnicity and gender and the challenge of changing stereotypes through transgression. Keywords: gender- and postcolonial theories, discourse analysis, print media, Caster Semen-ya, deviant body, ethnicity, intersexuality

[Collagenase injection in Dupuytren's disease, evaluation of the ultrasound assisted technique].

Since October 2011, the enzymatic lysis of Dupuytren's cord was introduced in Switzerland (Xiapex(®), Auxilium Pharmaceuticals, Pfizer). Here we present our first university experience and underline the major role of ultrasound during the injection. Between December 2011 and February 2013, 52 injections were performed to eliminate 43 Dupuytren's cords in 33 patients. The mean age of the patients was 64.4 ± 8.5 years. Complications were documented for each patient. Before, directly after and after a minimum of 6 months post-injection, the contracture of the treated joint was measured with use of a goniometer. The DASH score was evaluated after a minimum of 6 months and the patients were asked to subjectively evaluate the outcome of the treatment (very good, good, mild, poor) and whether they would reiterate it if necessary. Four skin defects, one lymphangitis, and one CRPS were responsible for a complication rate of 18%. There was no infection and no tendon rupture in the series. The mean MCP joint contracture was respectively 36.8 ± 27.4°, 3.5 ± 7.8° (gain of mobility compared to the preoperative situation 33.3°, P<0.001), and 8.4 ± 13.9° (gain 28.4°, P<0.001) respectively before, just after and at the long-term clinical control. The mean PIP joint contracture was respectively 36.5 ± 29.1°, 5.9 ± 6.7° (gain 30.6°, P<0.001), and 15.1 ± 13.8° (gain 21.4°, P<0.001) respectively before injection, just after and at the long-term clinical control. The DASH score decreased from 24 ± 14 to 7 ± 9 (P<0.001). Eighty-one per cent of the patients were satisfied or very satisfied of the treatment. All but two would reiterate the treatment if necessary. Ultrasound is able to target the injection of collagenase in order to reduce complications. The short-term results of this non-invasive therapy are very promising however comparison with conventional procedures is difficult as the long-term results are lacking.

Culture As a Process, the Process of the Lives of People and Their Behaviors

A Review of the 15th KUCES Lecture on Korean Culture entitled "Life as a Travel, Life as a Traum: Koreans' Way of Living in This Troubled World" presented by Professor Han Kyung-koo on November 20 [1999]