bluuebunny/crossref_metadata_2025 huggingface dataset:
The Politics of Pity: Domesticating Loss in a Russian Province
Authors: OUSHAKINE SERGUEI ALEX.
Published: May 2006

In this article, I explore how a group of women in a distant Russian province learned to live in the state of grief by creating a space for the traumatic experience in their daily order of things, their personal narratives, and public landscape. Using materials from my fieldwork in Siberia in 2001–03, I demonstrate how the Altai Regional Committee of the Soldiers' Mothers domesticated and privatized losses of their sons, which were caused by the Russian state's military politics of the last 20 years. By devising elaborate memorializating practices, the mothers managed to materialize evidence of their loss and suffering. It is precisely this collective and individual production of metonymies of death, I suggest, that not only became the main source of the Committee of the Soldiers' Mothers' new public identities but also acted as the principal vehicle of their politics of pity.
Modernity, Conservative Religious Movements, and the Female Subject: Newly Ultraorthodox Sephardi Women in Buenos Aires
Authors: JACOBSON SHARI
Published: May 2006

Conservative religious movements are multivalent. Depending on the context in which they are practiced, they are capable of signifying to their adherents modernity as much as tradition. Women who embrace these movements may find them meaningful and appealing precisely for this reason and irrespective of their apparent patriarchy. In this article, I examine the case of Argentine Jewish women of Syrian descent who have abandoned their self‐described traditional form of Jewish practice and embraced Jewish ultraorthodoxy. I focus on how local concerns about modernity and “Third Worldism” inform these transformations. In so doing, I demonstrate that women, as conservative religious actors, may be motivated by the same kinds of public sphere concerns that are normally attributed to their male counterparts.
Culturally Situated Design Tools: Ethnocomputing from Field Site to Classroom
Authors: EGLASH RON , BENNETT AUDREY , O'DONNELL CASEY , JENNINGS SYBILLYN , CINTORINO MARGARET
Published: May 2006

Ethnomathematics is the study of mathematical ideas and practices situated in their cultural context. Culturally Situated Design Tools (CSDTs) are web‐based software applications that allow students to create simulations of cultural arts—Native American beadwork, African American cornrow hairstyles, urban graffiti, and so forth—using these underlying mathematical principles. This article is a review of the anthropological issues raised in the CSDT project: negotiating the representations of cultural knowledge during the design process with community members, negotiating pedagogical features with math teachers and their students, and reflecting on the software development itself as a cultural construction. The move from ethnomathematics to ethnocomputing results in an expressive computational medium that affords new opportunities to explore the relationships between youth identity and culture, the cultural construction of mathematics and computing, and the formation of cultural and technological hybridity.
Sense and Sense Making in the Caucasus
Authors: GRANT BRUCE
Published: May 2006

A Small Corner of Hell: Dispatches from Chechnya. Anna Politkovskaya. Alexander Burry and Tatiana Tulchinsky, trans., with an introduction by Georgi Derluguian. Chicago: University of Chicago Press, 2003. 232 pp.

Bourdieu's Secret Admirer in the Caucasus:. World‐System Biography. Georgi M. Derluguian. Chicago: University of Chicago Press, 2005. 416 pp.

Chechnya: Life in. War‐Torn Society. Valery Tishkov. Tatiana Sokolova, trans., with. foreword by Mikhail Gorbachev. Berkeley: University of California Press, 2004. 284 pp.
A Companion to the Anthropology of American Indians
Authors: LOBO SUSAN
Published: May 2006

A Companion to the Anthropology of American Indians. Thomas Biolsi, ed. Williston, VT: Blackwell Publishers, 2004. 567 pp.
Accounting for Horror: Post‐Genocide Debates in Rwanda
Authors: LAME DANIELLE de
Published: May 2006

Accounting for Horror: Post‐Genocide Debates in Rwanda. Nigel Eltringham. London: Pluto Press, 2004. 232 pp.
For the Love of Women: Gender, Identity, and Same‐Sex Relations in a Greek Provincial Town
Authors: ALTAMIRANO DEBORAH R.
Published: May 2006

For the Love of Women: Gender, Identity, and Same‐Sex Relations in. Greek Provincial Town. Elisabeth Kirtsoglu. New York: Routledge, 2004. 192 pp.
Heritage of Value, Archaeology of Renown: Reshaping Archaeological Assessment and Significance
Authors: WEISS LINDSAY
Published: May 2006

Heritage of Value, Archaeology of Renown: Reshaping Archaeological Assessment and Significance. Clay Mathers, Timothy Darvill, and Barbara J. Little, eds. Gainesville: University Press of Florida, 2005. 339 pp.
Women at the Center: Life in a Modern Matriarchy
Authors: WEIX G. G.
Published: May 2006

Women at the Center: Life in. Modern Matriarchy. Peggy Reeves Sanday. Ithaca, NY: Cornell University Press, 2002. xv + 270 pp.
Commons + Borderlands: Working Papers on Interdisciplinarity, Accountability and the Flow of Knowledge
Authors: FISCHER MICHAEL M. J.
Published: May 2006

Commons + Borderlands: Working Papers on Interdisciplinarity, Accountability and the Flow of Knowledge. Marilyn Strathern. Wantage, Oxfordshire: Sean Kingston Publishing, 2004. 102 pp.
Black Hunger: Soul Food and America
Authors: ROUSE CAROLYN
Published: May 2006

Black Hunger: Soul Food and America. Doris Witt. Minneapolis: University of Minnesota Press, 2004. 292 pp.
Inbreeding, Incest, and the Incest Taboo: The State of Knowledge at the Turn of the Century
Authors: BARLOW KATHLEEN
Published: May 2006

Inbreeding, Incest, and the Incest Taboo: The State of Knowledge at the Turn of the Century. Arthur P. Wolf and William H. Durham, eds. Stanford: Stanford University Press, 2004. 228 pp.
"Our Child Doesn't Talk to Us Anymore": Alienation in Immigrant Chinese Families
Authors: Baolian Qin Desiree
Published: May 2006

Drawing on ethnographic data on two Chinese immigrant families over a five‐year period, I illustrate how and why growing alienation occurred in these families. My analysis shows that a host of developmental, immigration‐related, and cultural factors lead to growing alienation in parent—child relations. Social class also plays an important role in shaping family relations after migration. This article complicates understandings of the Chinese American home context and provides educational anthropologists with a useful framework to understand changing dynamics in immigrant families.
Democratization and Dispersion of Power: New Scenarios In Mexican Federalism
Authors: De Remes Alain
Published: May 2006

Focusing on political bargaining between the national and subnational realms, this article considers how the dispersion of power in different regions of a country may become a crucial factor shaping the rules of democratic governance. First, it analyzes changes in power dispersion of the last two decades in Mexico, highlighting how alternation in power at the national level in 2000 implemented horizontal checks and balances and revived a federal pact. Second, it shows that changes in the rules of the Mexican political system fostered a window of opportunity for new subnational actors to shape the national political agenda on re-engineering of the institutions of Mexican federalism.

Enfocándose en la negociación política entre el nivel nacional y el subnacional, este artículo reflexiona sobre cómo la dispersión de poder de diferentes regiones de un país puede convertirse en un factor crucial al modelar las reglas del gobierno democrático. Primero, analiza los cambios en la dispersión del poder en las últimas dos décadas de México, haciendo notar que la alternancia del poder a nivel nacional del 2000 implementó balances y contrapesos, y revivió el federalismo. Segundo, muestra que los cambios en las reglas del sistema político mexicano fomentaron el surgimiento de opciones para que nuevos actores subnacionales moldearan la agenda política nacional rediseñando las instituciones del federalismo mexicano.
Global Connections and Practicing Anthropology in the 21st Century
Authors: Hill Carole E. , Baba Marietta L.
Published: May 2006

This chapt er examines the major themes in the chapters that compromise this volume by discussing how the practice of anthropology across nations and regions of the world is changing as a result of globalization. Several themes are delineated that reflect a unity of purpose and concern about the development and structure of practicing and policy anthropology in the 21st century. Divergent viewpoints among the chapters are also examined. Through comparing and contrasting the major points of the chapters, four major interconnected themes are discussed. They are: 1) local/global transformations: challenge to the traditional; 2) the power of practicing anthropology in local/global contexts; 3) academic and practicing transformations, and 4) the closing gap between colonized and colonizer nations. These themes have important implications for the future of global practice and present challenges to the organization and uses of the products of anthropological inquiry.
Practicing Ethnology in Contemporary Russia
Authors: Yamskov Anatoly N.
Published: May 2006

The chapter reviews changing priorities of applied studies in Soviet and post‐Soviet Russia, presented on the background of institutional developments and changes in public status of ethnology in the country. Special emphasis is given to activities of the Institute of Ethnology and Anthropology (Moscow) in this field and to author–s personal experience in practicing ethnology during the last 15 years.
Applied Anthropology in Canada: Historical Foundations, Contemporary Practice and Policy Potentials
Authors: Ervin Alexander M. , Holyoak Lorne
Published: May 2006

Canadian domestic or on‐shore applied anthropology is examined beginning with historical background from the Nineteenth through to the mid‐Twentieth Century. It is only through the exponential growth of Canadian anthropology in the 1960s that its applied branches find their niches. Applied anthropology diversifies first into primary emphases on policy critiques, development, and northern and Aboriginal issues and then secondarily to resource industries, multiculturalism, immigration, health, and advocacy.
What's in the Name “Applied Anthropology”?: An Encounter with Global Practice
Authors: Baba Marietta L. , Hill Carole E.
Published: May 2006

This chapter is a reflective essay that explores the contextual influences upon the naming and non‐naming of applied anthropology in different nations and regions of the world. Using a historical and comparative method, the chapter is deliberately designed to present a perspective that does not originate from or end up in the United States. By comparing diverse contexts chronologically, the chapter suggests alternative ways of understanding the reasons why applied and practicing anthropology have evolved so distinctively in different places. The chapter suggests that applied and practicing anthropology, indeed all of anthropology, is inextricably bound to its historical and cultural contexts, meaning that there are important differences in the way the discipline is understood and practiced across different nations and regions. Moreover, historical shifts in context have resulted in important changes in the way the discipline is practiced over time. The chapter also argues that if processes of globalization are indeed transforming the nature of connectedness and boundaries across nations, then there are consequences for the distinctive forms of applied and practicing anthropology observed across nations, with an emphasis on those in the United States. The authors postulate that some of the differences observed between applied and practicing anthropology in the United States and elsewhere are beginning to blur, and that the unique model of applied anthropology that developed in the United States during the last quarter of the 20th century is destined to be transformed into one that is more integrated into the mainstream of the discipline and, indeed, into all of global anthropology.
Berlioz and the Pathological Fantastic: Melancholy, Monomania, and Romantic Autobiography
Authors: Brittan Francesca
Published: May 2006

Both the literary program of Berlioz's Symphonie fantastique and his personal letters dating from the year of the work's composition are suffused with the rhetoric of illness, detailing a maladie morale characterized by melancholy, nervous "exultation," black presentiments, and a malignant idee fixe.. Often mistakenly identified as a term new to the 1830s, the idee fixe has a considerably longer history, dating from the first decade of the nineteenth century when it appeared in the writings of French psychiatrists Etienne Esquirol and Jean-Etienne Georget. Both Esquirol's early writings on insanity and his seminal 1838 treatise identify mental "fixation" as the primary symptom of monomania, the most contentious and well-known mental disease of the period, and one with far-reaching implications not only for medicine but for Romantic literature, philosophy, and autobiography. Examination of the disease's early reception reveals that, well before Berlioz, the psychiatric terminology surrounding monomania had been absorbed into popular discourse. Malignant and humorous idee fixes appeared in cartoons, diaries, and newspaper articles from the 1810s onward, and in fictional works by Hoffmann, Duras, Scribe, Balzac, and others. Here, and in essays published in musical and literary journals of the period, monomania emerged as an increasingly aestheticized malady, and the idee fixe itself as a signal, not of mental debilitation, but of creative absorption and artistic inspiration. When Berlioz figured himself as a monomaniac, both in his personal writing and his symphonic program, he was responding to a discourse of "creative aberration" permeating Romantic literary and medical culture, and to a fashionable fascination with mental pathology. Berlioz was by no means the only artist of the period to diagnose himself with the symptoms of mental fixation. Musset, Janin, and Georges Sand also described themselves in monomaniacal terms in autobiographical "confessions" permeated with references to hallucination, fixation, and emotional pathology. Indeed, we can draw clear parallels between the veiled self-referentiality of the Fantastique and the autobiographical strategies of the Romantic Confession. Berlioz's "self-sounding" resonates with a host of other confessional autobiographies of the period and reflects the collapse between inspiration and insanity, between anatomy and aesthetics, underpinning early-nineteenth-century theories of genius.
Occasions and Nations in Brahms'sFest- und Gedenkspruche
Authors: Minor Ryan
Published: May 2006

Brahms's Fest- und Gedenkspruche have long been discussed and sometimes dismissed as an occasional work. But although many scholars have debunked this designation, pointing out that Brahms wrote the motets with no particular occasion in mind, a more salient description of the composition deserves further investigation: the motets are a work for occasions, rather than an occasional work. This article looks at the repercussions of this distinction by focusing on the motets' orientation around the world of plurals (in Benedict Anderson's words) that was both presupposed and fostered by a national culture of festivity in late-nineteenth-century Germany. For one, the title of Brahms's motets--Spruche--references the contemporary collections of sayings that sought to capture and disseminate the multiplicity of the Volk in the new German Kaiserreich. This emphasis on national identity as a localized, participatory act was well suited to the flurry of commemorative festivities taking place throughout the newly unified Germany; it also finds musical expression in the motets. In particular, Brahms makes programmatic use of the double chorus to illustrate processes of unification, narration, and historical continuity, all of which were crucial strategies in the attempt to buttress Germany's new political identity with mnemonic supports. And by setting biblical texts that promote a contractual memory between fathers and sons, Brahms depicts a community in which collective participation in remembering the national past serves as an optimistic bulwark against the centrifugal antagonisms that would soon beset the young German nation.
Healthcare utilization, quality of life and patient-reported outcomes during two years of GH replacement therapy in GH-deficient adults – comparison between Sweden, The Netherlands and Germany
Authors: Saller Bernhard , Mattsson Anders F , Kann Peter H , Koppeschaar Hans P , Svensson Johan , Pompen Marjolein , Koltowska-Häggström Maria
Published: May 2006

Objective: This study set out to determine the change in quality of life (QoL) and healthcare utilization during 2 years of growth hormone (GH) replacement therapy in adults with GH deficiency. Data were compared from three European countries.

Design: Analysis was made from KIMS, the Pfizer International Metabolic Database on adult GH deficiency.

Methods: QoL and healthcare utilization were measured at baseline and after 1 and 2 years of GH replacement in patient cohorts from Sweden (n = 302), The Netherlands (n = 103) and Germany (n = 98). QoL was assessed by the QoL-Assessment in Growth Hormone Deficient Adults (QoL-AGHDA) questionnaire, and the KIMS Patient Life Situation Form was used to evaluate healthcare utilization.

Results: QoL improved significantly (P < 0.0001) and comparably in all three cohorts. The improvement was seen during the first year of treatment and QoL remained improved during the second year. The number of days in hospital was reduced by 83% (P < 0.0001) during GH replacement. There were no country-specific differences either at baseline or during follow-up. The same was true for the number of days of sick leave (reduction of 63%; P = 0.0004). Significant reductions were recorded in the number of doctor visits in each of the three cohorts after 2 years of GH replacement (P < 0.05).

Conclusions: This study provides a detailed comparative analysis of GH replacement therapy in GHD patients in three European countries. Despite some differences in treatment strategies, the beneficial effects on QoL, patient-reported outcomes and healthcare utilization are essentially similar in the healthcare environment of Western European countries.
Thymus hyperplasia after resolution of hypercortisolism in ACTH-dependent Cushing’s syndrome: the importance of thymic vein catheterization
Authors: Neto Malebranche Berardo C Cunha , Machado Márcio Carlos , Mesquita Flávia , de Castro Musolino Nina Rosa , Toscanini Andrea Cecília , Ochman Gilberto , Cescato Valter Angelo S , Marino Raul , Teixeira Manoel Jacobsen
Published: May 2006

Thymic hyperplasia has been described after the resolution of hypercortisolism from several etiologies, causing great diagnostic dilemmas. We describe a case where the catheterization of the thymic vein was essential for the differential diagnosis of a thymic enlargement in an adrenalectomized patient with ACTH-dependent Cushing’s syndrome. The patient was a 48-year-old female with clinical and laboratorial data suggesting Cushing’s disease. She underwent a transsphenoidal surgery with no tumor visualization and no remission of the syndrome. Histopathological studies disclosed a normal pituitary. She underwent a bilateral adrenalectomy and 8 months later a chest CT showed an increase of left thymic lobe, which was previously non-existent. After a negative 111In-pentetreotide scintigraphy, the patient underwent simultaneous and bilateral catheterism of the petrosus sinuses and catheterization of the thymic and inominate veins and no ACTH gradient was shown among the sites of collection. She did not undergo thoracotomy and a follow-up was established. During the evolution, there was a spontaneous regression of the thymic lesion 38 months after the diagnosis. The ACTH gradient during the catheterization of thymic vein was essential for the differential diagnosis of the thymic enlargement tumor after hypercortisolism resolution in ACTH-dependent Cushing’s syndrome, especially in this case, where the ACTH source was occult, thus avoiding an invasive surgical procedure for a benign entity with spontaneous resolution.
Global Spectral UV‐Radiometer with Automatic Shadow Band
Authors: Rosales Alejandro , Pedroni Jorge V. , Tocho Jorge O.
Published: May 2006

A solar radiometer (GUV‐511 C, Biospherical Instruments Inc., San Diego, CA) with four UV channels has been operating at Trelew (43.2°S, 65.3°W), Argentina, since the austral spring of 1997. The Instrument provides global (direct + diffuse) irradiance on the horizontal plane year‐round, with a 1 min period. On 1 January 1999, an automatic shadow band was added to calculate diffuse and direct radiation. The period of the measurements was increased to 2 min to keep the same signal to noise (S:N) ratio. Once the direct radiation values were available for the 305 nm and 320 nm spectral bands, the total ozone value was calculated and results were compared with data provided by the U.S. National Aeronautics and Space Administration for the Total Ozone Mapping Spectrometer (TOMS) on the Earth Probe satellite. Results show a root‐mean‐square (RMS) deviation within 4% compared with that of TOMS, so the quality of results is considered to be quite good. The importance of regular calibration to maintain long‐term accuracy is stressed.
UVA and UVB Decrease the Expression of CD44 and Hyaluronate in Mouse Epidermis, which is Counteracted by Topical Retinoids
Authors: Calikoglu Emel , Sorg Olivier , Tran Christian , Grand Denise , Carraux Pierre , Saurat Jean‐Hilaire , Kaya Gürkan
Published: May 2006

The transmembrane glycoprotein CD44 is currently thought to be the main cell surface receptor for the glycosaminoglycan hyaluronate. We previously showed that (1) CD44 regulate keratinocyte proliferation; (2) topical retinoids dramatically increase the expression of CD44, hyaluronate and hyaluronate synthase (HAS)s in mouse epidermis; (3) topical retinaldehyde restores the epidermal thickness and CD44 expression which are correlated with clinical improvement in lichen sclerosus et atrophicus lesions; and (4) retinaldehyde‐induced proliferative response of keratinocytes is a CD44‐dependent phenomenon and requires the presence of HB‐EGF, erbB1 and matrix metalloproteinases. In this study, we analyzed the effect of UV irradiation on the levels of epidermal hyaluronate and CD44 in mice, as well as its potential prevention by topical retinoids. UVA (10 J/cm2) or UVB (1 J/cm>2) irradiation significantly decreased the expression of CD44 and hyaluronate in the epidermis of hairless mice after 2 h. Expression of both epidermal CD44 and hyaluronate was reconstituted within 24 h. Topical application of retinaldehyde for 3 days prior to UVA or UVB irradiation prevented the decrease of CD44 and hyaluronate expression. Topical retinol and retinoic acid also increased the basal levels of epidermal CD44 and hyaluronate, although their preventive effect on UV‐induced decrease of these molecules was less pronounced as compared to topical retinaldehyde. These data confirm the relationships between retinoid and CD44 pathways, although the primary target(s) of UV leading to CD44 and hyaluronate degradation remain to be elucidated.
Differential Gene Expression in Atlantic Salmon Infected with Lepeophtheirus salmonis
Authors: Fast Mark D. , Ross Neil W. , Muise Denise M. , Johnson Stewart C.
Published: May 2006

Lepeophtheirus salmonis is an ectoparasitic copepod that can cause serious disease outbreaks in salmonids. Previous work has shown that Atlantic salmon Salmo salar show very little, if any, tissue response to infection, whereas less-susceptible host species exhibit strong inflammatory responses. The objective of this study was to examine whether a low-level L. salmonis infection in the absence of a stress response would have an effect on expression of Atlantic salmon immune-related genes over time. The effects of low-level infection (approximately 8–11 lice/fish) on kidney tissue and head kidney leukocyte immune-related gene expression were studied at two postinfection time points. At this level of infection, there was no evidence of a cortisol stress response. By use of real-time polymerase chain reaction, constitutive expression of the major histocompatibility (MH) class I gene was shown to be 2–10-fold lower in infected Atlantic salmon head kidneys by 21 d postinfection (dpi) than in head kidneys of uninfected fish held under the same conditions. Conversely, by 14 and 21 dpi, constitutive MH class II expression was significantly increased (>10-fold) in infected fish. Constitutive expression of interleukin (IL) 1β also increased threefold in head kidneys of infected fish by 21 dpi; however, no differences were observed in cyclooxygenase (COX)-2 expression over the course of the infection. Adherent head kidney leukocytes from control Atlantic salmon showed an increase in MH class I and COX-2 expression after 3 h of lipopolysaccharide (LPS) stimulation for all three time points collected. The use of LPS stimulation on similar leukocytes from infected fish did not further increase levels of MH class I and COX-2 expression. This is the first report on host gene expression during an ectoparasitic copepod infection. The implications of these expression changes will be discussed with respect to the host–parasite relationship.
Molecular links between obesity and breast cancer
Authors: Lorincz A M , Sukumar S
Published: May 2006

Breast cancer continues to be a major health problem for women in the USA and worldwide. There is a need to identify and take steps to alter modifiable breast cancer risks. Conditions of obesity and overweight are risk factors that have reached epidemic proportions. This article reviews the evidence in the literature that test mechanism-based hypotheses which attempt to provide a molecular basis for a causal link between obesity and breast cancer risk, particularly the effects of metabolic syndrome and insulin resistance, peripheral estrogen aromatization in adipose tissue, and direct effect of adipokines. Future areas for study and implications for therapy are discussed.
Differential regulation of two forms of gonadotropin-releasing hormone messenger ribonucleic acid by gonadotropins in human immortalized ovarian surface epithelium and ovarian cancer cells
Authors: Choi Jung-Hye , Choi Kyung-Chul , Auersperg Nelly , Leung Peter C K
Published: May 2006

Although gonadotropin-releasing hormone (GnRH) has been shown to play a role as an autocrine/ paracrine regulator of cell growth in ovarian surface epithelium and ovarian cancer, the factors which regulate the expression of GnRH and its receptor in these cells are not well characterized. In the present study, we employed real-time PCR to determine the potential regulatory effect of gonadotropins on the expression levels of GnRH I (the mammalian GnRH), GnRH II (a second form of GnRH) and their common receptor (GnRHR) in immortalized ovarian surface epithelial (IOSE-80 and IOSE-80PC) cells and ovarian cancer cell lines (A2780, BG-1, CaOV-3, OVCAR-3 and SKOV-3). The cells were treated with increasing concentrations (100 and 1000 ng/ml) of recombinant follicle-stimulating hormone (FSH) or luteinizing hormone (LH) for 24 h. Treatment with FSH or LH reduced GnRH II mRNA levels in both IOSE cell lines and in three out of five ovarian cancer cell lines (A2780, BG-1 and OVCAR-3). A significant decrease in GnRHR mRNA levels was observed in IOSE and ovarian cancer cells, except CaOV-3 cells, following treatment with FSH or LH. In contrast, treatment with either FSH or LH had no effect on GnRH I mRNA levels in these cells, suggesting that gonadotropins regulate the two forms of GnRH and its receptor differentially. In separate experiments, the effect of gonadotropins on the anti-proliferative action of GnRH I and GnRH II agonists in IOSE-80, OVCAR-3 and SKOV-3 cells was investigated. The cells were pretreated with FSH or LH (100 ng/ml) for 24 h after which they were treated with either GnRH I or GnRH II (100 ng/ml) for 2 days, and cell growth was assessed by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay. Pretreatment of the cells with FSH or LH significantly reversed the growth inhibitory effect of GnRH I and GnRH II agonists in these cell types. These results provide the first demonstration of a potential interaction between gonadotropins and the GnRH system in the growth regulation of normal ovarian surface epithelium and its neoplastic counterparts.
Expression of tpo mRNA in thyroid tumors: quantitiative PCR analysis and correlation with alterations of ret, Braf , ras and pax8 genes
Authors: Di Cristofaro J , Silvy M , Lanteaume A , Marcy M , Carayon P , De Micco C
Published: May 2006

Immunocytochemistry (ICC) of thyroid peroxidase (TPO) using the monoclonal antibody MoAb47 has been used as malignancy marker on thyroid fine needle aspiration. However, little is known about the fate of TPO in thyroid carcinoma. We performed a qualitative PCR (Q-PCR) analysis to measure the expression of variants of tpo mRNA in 13 normal tissue samples, 30 benign tumors (BT), 21 follicular carcinomas (FC), 20 classical papillary carcinomas (PCc), 12 follicular variants of papillary carcinomas (PCfv) and nine oncocytic carcinomas (OC). We also studied mutations involving the ras, Braf, ret or pax8 genes. Results of Q-PCR were closely correlated with those of ICC (P < 0.0001; R = 0.59) and showed that overall tpo expression was lower in all carcinomas than in normal and BT (P < 0.05). The ratio tpo2 or tpo3 to tpo1 was inversed in follicular tumors. Genetic mutations were observed in 90% of PCc, 61.9% of FC, 41.7% of PCfv, 0% of OC and 10% in BT. pax8-ppar γ1 rearrangement was correlated with qualitative changes in tpo mRNA (P < 0.01). These results confirmed the decrease of TPO expression in 97% of thyroid carcinomas regardless of histological type and the overexpression of shorter splice variants in follicular tumors. Both reduction in quantity of TPO and impairment of its maturation process could account for the atypical immunohistochemical reaction of MoAb47 with TPO.
Activation of nuclear factor-κ B is linked to resistance to neoadjuvant chemotherapy in breast cancer patients
Authors: Montagut C , Tusquets I , Ferrer B , Corominas J M , Bellosillo B , Campas C , Suarez M , Fabregat X , Campo E , Gascon P , Serrano S , Fernandez P L , Rovira A , Albanell J
Published: May 2006

The nuclear factor (NF)-κB system is a promising anticancer target due to its role in oncogenesis and chemoresistance in preclinical models. To provide evidence in a clinical setting on the role of NF-κB in breast cancer, we aimed to study the value of basal NF-κB/p65 in predicting resistance to neoadjuvant chemotherapy, and to characterise the pharmacodynamic changes in NF-κB/p65 expression following chemotherapy in patients with locally advanced breast cancer. Pre- and post-chemotherapy tumour specimens from 51 breast cancer patients treated with anthracycline- and/or taxane-containing neoadjuvant chemotherapy were assayed by immunohistochemistry for NF-κB/p65 subcellular expression. We studied NF-κB/p65, a well-characterised member of the NF-κB family that undergoes nuclear translocation when NF-κB is activated. Activation of NF-κB (i.e. nuclear NF-κB/p65 staining in pre-therapy specimens) was linked to chemoresistance. Patients with NF-κB/p65 nuclear staining in pre-treatment samples had a 20% clinical response rate, while patients with undetected nuclear staining had a 91% response rate to chemotherapy (P = 0.002). Notably, four patients achieved a complete histological response and none of them had pre-treatment NF-κB/p65 nuclear staining. Moreover, the number of patients with NF-κB/p65 activation increased after chemotherapy exposure. It is concluded that NF-κB/p65 activation assayed by immunohistochemistry is a predictive factor of resistance to neoadjuvant chemotherapy in breast cancer patients. Moreover, NF-κB activation was inducible following chemotherapy in a proportion of breast cancer patients. These novel clinical findings strengthen the rationale for the use of NF-κB inhibitors to prevent or overcome chemoresistance in breast cancer.
Beyond peroxisome proliferator-activated receptor γ signaling: the multi-facets of the antitumor effect of thiazolidinediones
Authors: Weng J-R , Chen C-Y , Pinzone J J , Ringel M D , Chen C-S
Published: May 2006

Certain members of the thiazolidinedione (TZD) family of the peroxisome proliferator-activated receptor γ (PPARγ) agonists, such as troglitazone and ciglitazone, exhibit antitumor activities; however, the underlying mechanism remains inconclusive. Substantial evidence suggests that the antiproliferative effect of these TZD members in cancer cells is independent of PPARγ activation. To discern the role of PPARγ in the antitumor effects of TZDs, we have synthesized PPARγ-inactive TZD analogs which, although devoid of PPARγ activity, retain the ability to induce apoptosis with a potency equal to that of their parental TZDs in cancer cell lines with varying PPARγ expression status. Mechanistic studies from this and other laboratories have further suggested that troglitazone and ciglitazone mediate antiproliferative effects through a complexity of PPARγ-independent mechanisms. Evidence indicates that troglitazone and ciglitazone block BH3 domain-mediated interactions between the anti apoptotic Bcl-2 (B-cell leukemia/lymphoma 2) members Bcl-2/Bcl-xL and proapoptotic Bcl-2 members. Moreover, these TZDs facilitate the degradation of cyclin D1 and caspase-8-related FADD-like IL-l-converting enzyme (FLICE)-inhibitory protein through proteasome-mediated proteolysis, and down-regulate the gene expression of prostate-specific antigen gene expression by inhibiting androgen activation of the androgen response elements in the promoter region. More importantly, dissociation of the effects of TZDs on apoptosis from their original pharmacological activity (i.e. PPARγ activation) provides a molecular basis for the exploitation of these compounds to develop different types of molecularly targeted anticancer agents. These TZD-derived novel therapeutic agents, alone or in combination with other anticancer drugs, have translational relevance in fostering effective strategies for cancer treatment.
MicroRNA deregulation in human thyroid papillary carcinomas
Authors: Pallante P , Visone R , Ferracin M , Ferraro A , Berlingieri M T , Troncone G , Chiappetta G , Liu C G , Santoro M , Negrini M , Croce C M , Fusco A
Published: May 2006

MicroRNAs (miRNAs) are a class of small non-coding RNAs involved in a wide range of basic processes such as cell proliferation, development, apoptosis and stress response. It has recently been found that they are also abnormally expressed in many types of human cancer. We analyzed the genome-wide miRNA expression profile in human thyroid papillary carcinomas (PTCs) using a microarray (miRNACHIP microarray) containing hundreds of human precursor and mature miRNA oligonucleotide probes. Using this approach, we found an aberrant miRNA expression profile that clearly differentiates PTCs from normal thyroid tissues. In particular, a significant increase in miRNA (miR)-221, -222 and -181b was detected in PTCs in comparison with normal thyroid tissue. These results were further confirmed by northern blot and quantitative RT-PCR analyses. Moreover, RT-PCR revealed miR-221, -222 and -181b overexpression in fine needle aspiration biopsies corresponding to thyroid nodules, which were eventually diagnosed as papillary carcinomas after surgery. Finally, miR-221, -222 and -181b overexpression was also demonstrated in transformed rat thyroid cell lines and in mouse models of thyroid carcinogenesis. Functional studies, performed by blocking miR-221 function and by overexpressing miR-221 in human PTC-derived cell lines, suggest a critical role of miR-221 overexpression in thyroid carcinogenesis. In conclusion, these data, taken together, indicate an miRNA signature associated with PTCs, and suggest miRNA deregulation as an important event in thyroid cell transformation.
Effect of copper and thiomolybdates on bovine theca cell differentiation in vitro
Authors: Kendall N R , Marsters P , Guo L , Scaramuzzi R J , Campbell B K
Published: May 2006

Subfertility that will respond to appropriate copper supplementation is a widespread problem in the national dairy herd. The aims of this study were to determine the effect of copper and/or copper chelating thiomolybdates on LH-induced differentiation by looking at the effects on androgen production, steroidogenic enzymes (cytochrome P450 17α-hydroxylase and cytochrome P450 side-chain cleavage) and lysyl oxidase mRNA expression in cultured theca cells maintained under serum-free conditions.

The effect of thiomolybdates and copper on LH differentiation was investigated by supplementing (ammonium) tetrathiomolybdate to optimum theca cell culture media at 0–100 μg/ml, copper (chloride) at equimolar concentrations (0–51.6 μg/ml) or equimolar combinations of both media. Lysyl oxidase mRNA expression was investigated with semi-quantitative RT-PCR, whilst expression of cytochrome P450 17α-hydroxylase and cytochrome P450 side-chain cleavage mRNA was examined using real time PCR. Both PCRs used bovine specific primers and cell lysates obtained from bovine theca cells cultured for 6 days and in the presence or absence of the 100 μg/ml dose of thiomolybdate and equimolar copper thiomolybdate.

Thiomolybdate depressed androstenedione production in a dose-dependent manner at doses greater than 1 μg/ml at 96 h (P<0.05); doses above 20 μg/ml were all greatly reduced at all time points and at 192 h when related to numbers of cells (P<0.001). Copper alone had no effect at physiological doses, but the use of the equimolar copper thiomolybdate reversed the effect of tetrathiomolybdates on androstenedione production at the 20 μg/ml dose. Thiomolybdate supplementation, with and without copper, had no significant effect on the level of lysyl oxidase or cytochrome P450 side-chain cleavage expression. However, cytochrome P450 17α-hydroxylase expression was significantly increased (P<0.05) by tetrathiomolybdate, possibly due to a local regulatory system.

In conclusion, these results demonstrate that thiomolybdates can prevent LH-induced differentiation of bovine theca cells in vitro and that these effects can be ameliorated by copper supplementation. Our results also indicate that it is unlikely that the effects of thiomolybdate are mediated at the transcriptional level and further work is required to determine if thiomolybdate exerts its effects through post-translation processing or some other unrelated mechanism. Overall, these data support the hypothesis that copper responsive subfertility results from perturbation of the normal pattern of ovarian steroidogenesis.
Resistin regulates human choriocarcinoma cell invasive behaviour and endothelial cell angiogenic processes
Authors: Di Simone Nicoletta , Di Nicuolo Fiorella , Sanguinetti Maurizio , Castellani Roberta , D’Asta Marco , Caforio Leonardo , Caruso Alessandro
Published: May 2006

Resistin is a novel hormone that is secreted by human adipocytes and mononuclear cells and is probably associated with insulin resistance. Recently, resistin has been postulated to play a role in pregnancy, and resistin gene expression has been observed in placental tissues. However, it is still not known if resistin is able to affect trophoblast functions and development. Therefore, we investigated the hypothesis that resistin might regulate trophoblast production of matrix metalloproteinases (MMPs), the tissue inhibitors of metalloproteinases (TIMPs), trophoblast invasive behavior and the angiogenic processes.

In human choriocarcinoma cells (BeWo), resistin (10–100 ng/ml) enhanced both MMP-2 protein and mRNA expression, significantly reduced TIMP-1 and TIMP-2 and increased trophoblast-like cell invasiveness.

We analyzed the effect of resistin on an in vitro angiogenesis system for endothelial cells (HUVEC) and we evaluated its ability to modulate the secretion of an angiogenic factor, vascular endothelial growth factor (VEGF). Our data showed that resistin induced VEGF production and we observed that the addition of resistin stimulated endothelial cell tube formation.

These findings suggest that resistin might be able to induce BeWo cell invasiveness and to contribute to the control of placental vascular development.
The effect of exercise training on adiponectin receptor expression in KKAy obese/diabetic mice
Authors: Huang Hu , Iida Kaoruko Tada , Sone Hirohito , Yokoo Tomotaka , Yamada Nobuhiro , Ajisaka Ryuichi
Published: May 2006

Adiponectin is an adipocyte-derived factor that plays a pivotal role in lipid and glucose metabolism. Recently, two types of adiponectin receptors (AdipoR1 and AdipoR2) were identified. We investigated whether exercise training (ET) or dietary restriction (DR) affects the expression of adiponectin receptors in skeletal muscle and liver, thereby improving glucose and lipid metabolism in KKAy mice. KKAy mice were subjected to 8 weeks of exercise training or food restriction. Following the experimental protocol, an intravenous glucose tolerance test and an intraperitoneal insulin tolerance test were performed in addition to the measurement of blood lipid and adiponectin concentrations. The mRNA levels of adiponectin, adiponectin receptors and genes that are putatively regulated by the adiponectin receptors were also analyzed. Both the 8-week exercise training and food restriction protocol improved insulin resistance in KKAy mice but did not alter plasma adiponectin concentration nor its mRNA expression. In comparison with C57BL/6 mice, AdipoR1 expression level was significantly decreased in skeletal muscle and AdipoR2 expression level was significantly increased in the liver in KKAy mice. After the 8-week experimental protocol, the expression level of AdipoR1 mRNA was approximately 1.8-fold greater in the skeletal muscle and 1.3-fold greater in the liver, and the level of AdipoR2 mRNA was 30% less in the liver of the ET group as compared with the control group. Additionally, in the ET group, mRNA expression of acyl coenzyme A-oxidase and carnitine palmitoyl transferase 1 (CPT1) was greater in the liver but not in skeletal muscle. In contrast, no significant changes were observed in the expression of genes encoding the adiponectin receptors in addition to other genes except for CPT1 in the DR group. These findings suggest that chronic exercise training affects the expression level of adiponectin receptors thereby improving insulin resistance in KKAy mice.
Tissue inhibitor of metalloproteinase 1 expression and secretion are induced by β-adrenergic stimulation in 3T3-L1 adipocytes
Authors: Kralisch S , Lossner U , Bluher M , Paschke R , Stumvoll M , Fasshauer M
Published: May 2006

Tissue inhibitor of metalloproteinase (TIMP)-1 is an adipocytokine upregulated in obesity which might promote adipose tissue development. In the current study, the impact of the β-adrenergic agonist isoproterenol on TIMP-1 gene expression and secretion was determined in 3T3-L1 adipocytes. Interestingly, isoproterenol increased TIMP-1 secretion 2.7-fold. Furthermore, isoproterenol induced TIMP-1 mRNA in a time- and dose-dependent fashion with significant effects observed as early as 1 h after effector addition and at concentrations as low as 1 μM isoproterenol. Significant isoproterenol-induced upregulation of TIMP-1 mRNA could also be found in immortalized brown adipocytes. Inhibitor experiments confirmed that the positive effect of isoproterenol on TIMP-1 is mediated via β-adrenergic receptors and protein kinase A. Moreover, increasing cAMP levels with forskolin or dibutyryl-cAMP was sufficient to stimulate TIMP-1 synthesis. Insulin induced basal TIMP-1 mRNA, but did not significantly influence forskolin-induced TIMP-1 expression. Taken together, we demonstrate that TIMP-1 expression and secretion are selectively upregulated in adipocytes by β-adrenergic agonists via a classic Gs-protein-coupled pathway.
Cardiac concentric remodelling induced by non-aromatizable (dihydro-)testosterone is antagonized by oestradiol in ovariectomized rats
Authors: Tivesten Å , Bollano E , Nyström H C , Alexanderson C , Bergström G , Holmäng A
Published: May 2006

Previous studies on the cardiovascular effects of androgens in females, most of them using testosterone treatment, have yielded conflicting results. Testosterone is metabolized into oestradiol (E2) and dihydrotestosterone (DHT) within cardiovascular tissues. The aim of the present study was to explore the cardiovascular effects exerted by E2 and the non-aromatizable androgen DHT and to study possible interactions between these in female rats. Ovariectomized rats were treated with DHT, E2, or DHT+E2 for 6 weeks. DHT increased left-ventricular posterior wall thickness, assessed by echocardiography, whereas left-ventricular dimension, as well as total heart weight and calculated left-ventricular mass, were unchanged. DHT also increased the levels of insulin-like growth factor-I mRNA in the left ventricle. E2 abolished the effect of DHT on left-ventricular remodelling and insulin-like growth factor-I mRNA when the two treatments were given in combination. E2 also reduced androgen receptor mRNA levels in the heart. Neither E2 nor DHT changed blood pressure measured by telemetry. In conclusion, treatment with the endogenous non-aromatizable androgen DHT causes cardiac concentric remodelling in ovariectomized rats, possibly mediated by increased local levels of insulin-like growth factor-I. The effect of DHT on cardiac wall thickness was antagonized by E2, possibly through downregulation of cardiac androgen receptors. These mechanisms may be of importance for the concentric left-ventricular geometric pattern developing in women after menopause.
Identification of new gonadotrophin-releasing hormone partial agonists
Authors: Leaños-Miranda Alfredo , Ulloa-Aguirre Alfredo , Cervini Laura A , Janovick Jo Ann , Rivier Jean , Conn P Michael
Published: May 2006

GnRH agonists or antagonists are currently utilized as therapeutic agents in a number of diseases. A side-effect of prolonged treatment with GnRH analogues is hypoestrogenism. In this study, we tested the in vitro potency of different GnRH analogues originally found to be partial agonists (i.e. analogues with decreased efficacy for activating or stimulating their cognate receptor) as well as novel analogues, to identify compounds that might potentially be useful for partial blockade of gonadotrophin release. Cultured COS-7 cells transiently expressing the rat or human GnRH receptor (GnRHR) were exposed to increasing concentrations (10−8 to 10−5 M) of GnRH analogues (c(4–10)[Asp4,DNal6,Dpr10]-GnRH; c(4–10) [Dpr4,DNal6,Asp10]-GnRH; c(4–10)[Cys4,10,DNal6]-GnRH; c[Eaca1,DNal6]-GnRH; c[Gly1,DNal6]-GnRH; c[βAla1,DTrp6]-GnRH; c[Dava1,DNal6]-GnRH; c[Gaba1, DNal6]-GnRH), and the ability of these analogues to provoke or antagonize GnRH-stimulated inositol phosphate production was assessed.

With both human and rat GnRHRs, c[Eaca1,DNal6]-GnRH, c[Gly1,DNal6]-GnRH, c[βAla1,DTrp6]-GnRH and c[Dava1,DNal6]-GnRH exhibited partial agonist activity (35–87% of the maximal efficacy shown by 10−6 M GnRH), whereas c[Gaba1,DNal6]-GnRH behaved as a partial agonist with the human GnRHR and as full agonist with the rat GnRHR. c(4–10)[Asp4, DNal6,Dpr10]-GnRH and c(4–10)[Dpr4,DNal6,Asp10]-GnRH exhibited full antagonist activity with both GnRHRs, and c(4–10) [Cys4,10,DNal6]-GnRH was a weak, partial agonist with the human GnRHR and a full antagonist with the rat GnRHR. With the exception of c[Gaba1,DNal6]-GnRH stimulation of the human GnRHR, and c[Dava1,DNal6]-GnRH and c[Gaba1, DNal6]-GnRH stimulation of the rat GnRHR, all partial agonists also exhibited antagonist activity in the presence of the exogenous full agonist.

The results demonstrate that structurally similar analogues display variable potencies and efficacies in vitro for a specific GnRHR as well as for the human versus the rat GnRHR. Their ultimate in vivo usefulness to treat clinical conditions in which complete suppression of gonadotroph activity is not required remains to be investigated.