bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation Function 1 of Glucocorticoid Receptor Binds TATA-Binding Protein in Vitro and in Vivo
Authors: Copik Alicja J. , Webb M. Scott , Miller Aaron L. , Wang Yongxin , Kumar Raj , Thompson E. Brad
Published: February 2006

The mechanism through which the glucocorticoid receptor (GR) stimulates transcription is still unclear, although it is clear that the GR affects assembly of the transcriptional machinery. The binding of the TATA-binding protein (TBP) to the TATA-box is accepted as essential in this process. It is known that the GR can interact in vitro with TBP, but the direct interaction of TBP with GR has not been previously characterized quantitatively and has not been appreciated as an important step in assembling the transcriptional complex. Herein, we demonstrate that the TBP-GR interaction is functionally significant by characterizing the association of TBP and GR in vitro by a combination of techniques and confirming the role of this interaction in vivo. Combined analysis, using native gel electrophoresis, sedimentation equilibrium, and isothermal microcalorimetry titrations, characterize the stoichiometry, affinity, and thermodynamics of the TBP-GR interaction. TBP binds recombinant GR activation function 1 (AF1) with a 1:2 stoichiometry and a dissociation constant in the nanomolar range. In vivo fluorescence resonance energy transfer experiments, using fluorescently labeled TBP and various GR constructs, transiently transfected into CV-1 cells, show GR-TBP interactions, dependent on AF1. AF1-deletion variants showed fluorescence resonance energy transfer efficiencies on the level of coexpressed cyan fluorescent protein and yellow fluorescent protein, indicating that the interaction is dependent on AF1 domain. To demonstrate the functional role of the in vivo GR-TBP interaction, increased amounts of TBP expressed in vivo stimulated expression of GR-driven reporters and endogenous genes, and the effect was also specifically dependent on AF1.
In Vitro Evidence that Upstream of N-ras Participates in the Regulation of Parathyroid Hormone Messenger Ribonucleic Acid Stability
Authors: Dinur Maya , Kilav Rachel , Sela-Brown Alin , Jacquemin-Sablon Helene , Naveh-Many Tally
Published: February 2006

Calcium and phosphate regulate PTH gene expression posttranscriptionally through the binding of trans-acting factors to a defined cis-acting instability element in the PTH mRNA 3′-untranslated region (UTR). We have previously defined AU-rich binding factor 1 as a PTH mRNA binding and stabilizing protein. We have now identified, by affinity chromatography, Upstream of N-ras (Unr) as another PTH mRNA 3′-UTR binding protein. Recombinant Unr bound the PTH 3′-UTR transcript, and supershift experiments with antibodies to Unr showed that Unr is part of the parathyroid RNA binding complex. Finally, because there is no parathyroid cell line, the functionality of Unr in regulating PTH mRNA levels was demonstrated in cotransfection experiments in heterologous human embryonic kidney 293 cells. Depletion of Unr by small interfering RNA decreased simian virus 40-driven PTH gene expression in human embryonic kidney 293 cells transiently cotransfected with the human PTH gene. Overexpression of Unr increased the rat full-length PTH mRNA levels but not a PTH mRNA lacking the terminal 60-nucleotide cis-acting protein binding region. Unr also stabilized a chimeric GH reporter mRNA that contained the rat PTH 63-nucleotide cis-acting element but not a truncated PTH element. Therefore, Unr binds to the PTH cis element and increases PTH mRNA levels, as does AU-rich binding factor 1. Our results suggest that Unr, together with the other proteins in the RNA binding complex, determines PTH mRNA stability.
Richard Hakluyt's Navigations in Time: History, Epic, and Empire
Authors: Sacks David Harris
Published: February 2006

David Harris Sacks, Richard F. Scholz Professor of History and Humanities at Reed College, is author of, among other works, The Widening Gate: Bristol and the Atlantic Economy, 1450–1700 (1991) and editor, with Donald R. Kelley, of The Historical Imagination in Early Modern Britain: History, Rhetoric, and Fiction, 1500–1800 (1997) and of Ralph Robynson's translation of Thomas More's Utopia (1999). He is currently engaged in projects exploring the place of Richard Hakluyt's career in the making of the Atlantic world and the development of markets and publics in early modern Europe.
The Tragedy of Nobility on the Seventeenth-Century Stage
Authors: Quint David
Published: February 2006

David Quint is George M. Bodman Professor of English and Comparative Literature at Yale University. His most recent books are Montaigne and the Quality of Mercy: Ethical and Political Themes in the “Essais” (1998) and Cervantes's Novel of Modern Times: A New Reading of “Don Quijote” (2003). His essays “A Reconsideration of Montaigne's Des Cannibales” and “Narrative Interlace and Narrative Genres in Don Quijote and the Orlando Furioso” appeared in the December 1990 and September 1997 issues of MLQ.
The Diplomatic Moment: Representing Negotiation in Early Modern Europe
Authors: Hampton Timothy
Published: February 2006

Timothy Hampton is professor of comparative literature and French at the University of California, Berkeley. His work focuses on the relationship between literature and political discourse in early modern Europe. He is working on a book tentatively titled Fictions of Embassy: Literary Diplomacy from Machiavelli to Leibniz. His essay “On the Border: Geography, Gender, and Narrative Form in the Heptaméron” appeared in the December 1996 issue of MLQ.
Italy's Role in Mediterranean Security and the Fight Against Terrorism
Authors: Fini Gianfranco
Published: February 2006

Gianfranco Fini is foreign minister of Italy.
The Middle East: Unbearable Status Quo versus Unpredictable Changes
Authors: Kumaraswamy P. R.
Published: February 2006

P. R. Kumaraswamy is associate professor at the Centre for West Asian and African Studies, School of International Studies, Jawaharlal Nehru, New Delhi, India.
Pax Mediterraneo
Authors: Savir Uri
Published: February 2006

Uri Savir is president of the Peres Center for Peace, Tel Aviv. He formerly was chief negotiator for Israel throughout the Oslo process, director general of the Israeli Foreign Ministry, and member of the Israeli Parliament for the Center Party.
The Cultural Underpinnings of Politics: Iran and the United States
Authors: Bill James A.
Published: February 2006

James A. Bill is professor emeritus of government at the College of William and Mary.
The Imperial Lure: Nation Building as a US Response to Terrorism
Authors: Carpenter Ted Galen
Published: February 2006

Ted Galen Carpenter, vice president for defense and foreign policy studies at the Cato Institute, is the author or editor of seventeen books on international affairs, including Peace and Freedom: Foreign Policy for a Constitutional Republic.
Turkey's Policies Toward Kurdistan-Iraq and Iraq: Nationalism, Capitalism, and State Formation
Authors: Olson Robert
Published: February 2006

Robert Olson is professor of Middle East politics at the University of Kentucky.
Implications of the Accession of Cyprus to the European Union for Greek-Turkish and Euro-Turkish Relations
Authors: Melakopides Costas
Published: February 2006

Costas Melakopides is associate professor of political science at the University of Cyprus and president of the Cyprus Institute of Mediterranean, European, and International Studies.
High-Pressure 129Xe NMR Study of the Intermolecular Interaction of Xenon Confined in Activated Carbon Fiber (ACF)
Authors: Ueda Takahiro , Omi Hironori , Yukioka Takanori , Eguchi Taro
Published: February 2006

The pressure dependence of a 129Xe chemical shift (δ) and the local density of xenon adsorbed in activated carbon fiber (ACF) with slit-pore widths of 0.7–1.1 nm was investigated using in-situ high-pressure 129Xe NMR. 129Xe chemical shift values below 0.025 MPa change linearly with equilibrium pressure. The initial slope of the pressure dependence of δ led to a shift value at zero pressure, δS′, which approximately reflects the xenon–wall interaction. A statistical model incorporating the xenon–wall interaction well interprets the dependence of δS′ on the pore width. Furthermore, in a higher-pressure region, the density dependence of the chemical shift led to the xenon–xenon interaction via the virial coefficients of the chemical shift up to the second order on density (the third-virial coefficient). The second-virial coefficient (a coefficient for the linear term of density) depended on the pore width. Increasing the slit width from 0.7 to 1.1 nm increased the second-virial coefficient, δ1, from 42 × 10−3 to 78 × 10−3 ppm kg−1 m3, suggesting that the space accessible by the surrounding xenon atoms increases when the slit width increases. This aspect reveals the size effect of the xenon–xenon interaction in nanospace.
Intercalation of Glucosamine and Chitosan into Layered Zirconium Phosphates
Authors: Hayashi Aki , Nakabayashi Yui , Yasutomi Junko , Nakayama Hirokazu , Tsuhako Mitsutomo
Published: February 2006

Glucosamine was directly intercalated into γ-zirconium phosphate (γ-ZrP). The intercalation compound with a monolayer structure was obtained by the interaction between the 2-amino group of glucopyranose and the phosphate group in γ-ZrP. The uptake amount depended on the concentration of the glucosamine aqueous solution rather than reaction time, and reached 0.9 mmol per gram of γ-ZrP at the maximum. On the other hand, chitosan, polysaccharide of glucosamine, could be intercalated into alkylamine-intercalated γ-ZrP as the host compound. Chitosan-intercalated γ-ZrP showed two phases with different interlayer distances. It was confirmed from 13C CP/MAS NMR spectra that chitosan exists in the interlayer region of γ-ZrP for both phases.
Aluminium-27 NMR Investigation of the 2-Hydroxyethyl(trimethyl)ammonium Aluminosilicate Solution
Authors: Samadi-Maybodi Abdolraouf , Goudarzi Nasser , Naderi-Manesh Hossein
Published: February 2006

Alkaline solutions containing both silicate and aluminate ions are of considerable research interest inter alia because of their involvement in the synthesis of zeolites. 27Al NMR spectra of alkaline aluminosilicate solutions generally show a maximum of five broad bands. In the present work, we use 27Al NMR to characterize aluminosilicate solutions with different Al/Si ratios using 2-hydroxyethyl(trimethyl)ammonium as a cation template, no alkaline metals are used for preparation of aluminosilicate solutions. To understand the reaction between silicate and aluminate ions in this system, the evolutions of 27Al NMR spectra with time are investigated.
Luminescence of Copper(I) Dinuclear Complexes Bridged by Diphosphine Ligands
Authors: Tsukuda Toshiaki , Nakamura Ayaka , Arai Takashi , Tsubomura Taro
Published: February 2006

Mixed-ligand dinuclear Cu(I) complexes containing both diimine and diphosphine ligands have demonstrated interesting photophyisical properties; the complexes are emissive in solution at room temperature, even with 1,10-phenanthroline (phen) lacking a 2,9-substituted group.
Determination of the Solubility Product of CH3COONa in Propylene Carbonate and Standard Gibbs Energies of Ion Transfer Using a Poly(acrylamide) Membrane Ion-Selective Electrode Based on Benzo-15-crown-5
Authors: Ren Jujie , Nakashima Junichi , Nakamura Toshio
Published: February 2006

A Benzo-15-crown-5 modified poly(acrylamide) membrane coated platinum electrode is successfully used to determine the solubility product of CH3COONa in propylene carbonate. The standard Gibbs energies of Na+ and CH3COO− transfer from water to propylene carbonate are obtained. The datum of CH3COO− is reported for the first time.
Conversion of 2-Aminoethanethiolate (aet) to 2-Benzoylaminoethanethiolate (L) in a S-Bridged Diruthenium(II) Complex Composed of Two cis-[Ru(bpy)2] Units. Crystal Structures of ΔΔ/ΛΛ-[{Ru(bpy)2}2(μ-Haet)2]4+ and ΔΔ/ΛΛ-[{Ru(bpy)2}2(μ-L)2]2+
Authors: Matsuura Noriyuki , Kawamoto Tatsuya , Konno Takumi
Published: February 2006

A diruthenium(II) complex, ΔΔ/ΛΛ-[{Ru(bpy)2}2(μ-L)2]2+ (ΔΔ/ΛΛ-[2]2+), in which two cis-[Ru(bpy)2]2+ units are bridged by two S atoms from two 2-benzoylaminoethanethiolate (L) ligands, was synthesized by the reaction of ΔΔ/ΛΛ-[{Ru(bpy)2}2(μ-Haet)2]4+ (aet = 2-aminoethanethiolate; ΔΔ/ΛΛ-[1]4+) with benzoyl chloride in the presence of a base. The molecular structure and electrochemical properties of ΔΔ/ΛΛ-[2]2+ were discussed in comparison with those of ΔΔ/ΛΛ-[1]4+.
Chemical and Genetic Differentiation of Ligularia pleurocaulis in Northwestern Yunnan and Southwestern Sichuan Provinces of China
Authors: Nagano Hajime , Iwazaki Yukiko , Gong Xun , Shen Yuemao , Kuroda Chiaki , Hanai Ryo
Published: February 2006

Intra-specific diversity of Ligularia pleurocaulis was examined from both chemical and genetic aspects, using furanoeremophilanes as the chemical index and the nucleotide sequences in the atpB-rbcL and the ITS1 regions as the genetic index. Four samples of L. pleurocaulis were collected in northwestern Yunnan, and six in southwestern Sichuan. From the ethanol extracts of the roots of all of the samples, four compounds, 6β-angeloyloxy- and 6β-tigloyloxy-furanoeremophil-1(10)-enes, and 6β-angeloyloxy- and 6β-tigloyloxy-furanoeremophil-1(10)-en-3β-ols were isolated. Further, 3β-angeloyloxyfuranoeremophil-1(10)-en-6β-ol and furanoligularenone were isolated from the Yunnan and the Sichuan samples, respectively. Two variants were found for the atpB-rbcL sequence. Base multiplicity in the ITS1 region was observed at only a few positions in the Yunnan samples, whereas it was observed at about 10 positions for the Sichuan samples. These results show that L. pleurocaulis is diverse, both chemically and genetically, and that plants in northwestern Yunnan and those in southwestern Sichuan can be distinguished by their chemical and genetic indexes.
Substituent Effects on the Ground-State Properties of Naphthalene-Based Analogues of Salicylideneaniline in Solution
Authors: Ohshima Asuka , Momotake Atsuya , Arai Tatsuo
Published: February 2006

Substituent effects on the ground-state properties of seven naphthalene analogues of salicylideneaniline (1–7) were studied by comparison of both steady-state and transient absorption spectra. The naphthalene-based salicylideneanilines 1–5 were prepared from 2-hydroxy-1-naphthaldehyde and corresponding amines. The UV absorption spectra of 1–5 were largely dependent on the substituent group on the amino group. Transient absorption studies revealed that the introduced naphthyl group in 1–5 prolonged the lifetime of 1Ktrans in non-polar solvent probably due to the formation of intramolecular hydrogen bonding between nitrogen and C–H hydrogen on the naphthyl group. In acetonitrile, the lifetimes of 1–6 are much longer than those in benzene, probably because the zwitterionic forms are stabilized in polar solvents, whereas the much shorter lifetime in ethanol suggests that 1Ktrans undergoes the solvent assisted re-enolizaiton reaction in ethanol.
Formation of Pyrene Dimer Radical Cation at the Minor Groove of DNA
Authors: Kawai Kiyohiko , Kimura Takumi , Yoshida Hiroko , Sugimoto Akira , Tojo Sachiko , Fujitsuka Mamoru , Majima Tetsuro
Published: February 2006

To arrange pyrene at the minor groove of DNA, we synthesized a nucleoside derivative possessing a pyrene group on guanine N2. Doubly pyrene-modified duplex DNA was synthesized and the formation rates of the pyrene dimer radical cation were measured upon one-electron oxidation during pulse radiolysis. For all of the DNA studied here, the formation of a pyrene dimer radical cation was accomplished quickly, within 20 micro seconds after a 8-ns electron pulse during pulse radiolysis. The results show that the minor groove of DNA offers a good space for the formation of pyrene dimer radical cations.
Synthesis of Helicenediamine Oligomers and Their Formation of Multilayer Structures in Aqueous Solvents
Authors: Mizukami Jun , Sugiura Hiroki , Yamaguchi Masahiko , Mushiake Kumiko
Published: February 2006

Optically active polyamine oligomers containing three to six (P)-5,8-bis(aminomethyl)-1,12-dimethylbenzo[c]phenanthrenes were synthesized employing the two-directional chain extension method. It was critical for the effective coupling of amines and aldehydes to precipitate imine intermediates using the appropriate solvents. UV, CD, fluorescent, and NMR spectroscopic studies revealed that the above-mentioned oligomers form multilayer structures in aqueous solvents, while they form random coil structures in methanol. Such layer structures contained helicene dyads with an anti-conformation in which the BC-rings of helicenes were stacked on each other, and 1,12-dimethyl groups were arranged in the opposite direction. A diastereomeric trimer was also synthesized, the layer structure of which was different from that of the parent trimer. The stereochemistry of the helicene moiety influenced the layer structure.
Immobilization of Glycoconjugate Polymers on Cellulose Membrane for Affinity Separation
Authors: Miyagawa Atsushi , Kasuya Maria Carmelita Z , Hatanaka Kenichi
Published: February 2006

Membranes with immobilized glycoconjugate polymers were prepared and lectin adsorption was evaluated. Glycoconjugate polymers having the carbohydrates, lactose, and mannose, the amino groups of the reaction point, and a fluorescence label were synthesized, while cellulose membranes were carboxymethylated. The content of the carboxyl group was evaluated by titration. Subsequently, the glycoconjugate polymers were immobilized on the cellulose membranes by amide linkages formed by condensation reaction. Analysis of the luminescence of the fluorescence labels revealed that the glycoconjugate polymers had been immobilized on the cellulose membranes. Examination of lectin adsorption by the glycoconjugate polymer on the membrane revealed that the membrane with the immobilized mannose-having polymer adsorbed 53% of the applied ConA and the membrane with the immobilized lactose-having polymer adsorbed 83% of the applied RCA120. The membrane with immobilized glycoconjugate polymers selectively adsorbed each lectin. In addition, membranes with different types of immobilized glycoconjugate polymers were used in stacks, and in this case, the membranes selectively adsorbed lectin. Thus, membranes with immobilized glycoconjugate polymers efficiently and easily purify lectin.
Total Polyphenol Intake Estimated by a Modified Folin–Ciocalteu Assay of Urine
Authors: Roura Elena , Andrés-Lacueva Cristina , Estruch Ramon , Lamuela-Raventós Rosa M
Published: February 2006

Background: Plant polyphenols have been studied largely because of the possibility that they might underlie the protective effects afforded by fruit and vegetable intake against cancer and other chronic diseases. Measurement of polyphenol content excreted in urine as an indicator of polyphenol consumption may offer a routine screening method that could be used for these pathologies.

Methods: Thirty-six healthy volunteers each received 2 interventions, one with a polyphenol-rich food (cocoa beverage) and one with a polyphenol-free food (milk) as a control, in a randomized cross-over design with 1-week intervals. The total polyphenol content excreted in urine during the 6 h after consumption of the test meals was measured by a modified Folin-Ciocalteu assay after sample cleanup by solid-phase extraction.

Results: The mean (SD) concentrations of polyphenols excreted in the urine 6 h after consumption of the test meals differed significantly: 140.95 (49.27) mg catechin/g of creatinine after the polyphenol-rich meal vs 90.43 (46.07) mg catechin/g of creatinine after the control meal (P <0.05).

Conclusions: This method allows analysis of a large number of samples per day, which is ideal for use in epidemiologic studies and may enable estimation of polyphenol consumption and determination of their possible role in preventing of certain pathologies, such as cancer, cardiovascular and degenerative diseases.
Diet Composition of Young‐of‐the‐Year Bluefish in the Lower Chesapeake Bay and the Coastal Ocean of Virginia
Authors: Gartland James , Latour Robert J. , Halvorson Aimee D. , Austin Herbert M.
Published: February 2006

The lower Chesapeake Bay and coastal ocean of Virginia serve as an important nursery area for bluefish Pomatomus saltatrix. Describing the diet composition of young‐of‐the‐year (hereafter, age‐0) bluefish in this region is essential to support current Chesapeake Bay ecosystem modeling efforts and to contribute to the understanding of the foraging ecology of these fish along the U.S. Atlantic coast. The stomach contents of 404 age‐0 bluefish collected from the lower Chesapeake Bay and adjacent coastal zone in 1999 and 2000 were examined as part of a diet composition study. Age‐0 bluefish foraged primarily on bay anchovies Anchoa mitchilli, striped anchovies Anchoa hepsetus, and Atlantic silversides Menidia menidia. Other fishes such as striped bass Morone saxatilis, white perch Morone americana, Atlantic menhaden Brevoortia tyrannus, and bluefish were seasonally important. Crab zoea and megalope Callinectes spp. and amphipods Gammarus spp. were the most important invertebrate prey. A seasonal dietary shift from Atlantic silversides to anchovies was evident. Overall, small pelagic and littoral schooling fishes, particularly engraulids and atherinids, predominated in the diet of the age‐0 bluefish collected for this study. Although the results presented here were similar to the diet composition of age‐0 bluefish reported in previous studies, some notable differences were probably due to spatial and temporal differences in prey assemblages.
Tumorigênese hipofisária
Authors: Bronstein Marcello D. , Melmed Shlomo
Published: February 2006

Os tumores hipofisários, adenomas na sua quase totalidade, representam de 10% a 15% das neoplasias intracranianas (1) e são encontrados em até 27% de autópsias não selecionadas, como achado incidental (2). Morfologicamente são classificados em microadenomas (< 1cm de diâmetro) e macroadenomas, que podem ser circunscritos, invasivos e/ou expansivos. Do ponto de vista funcional, são divididos em adenomas secretores (de PRL, GH, ACTH, TSH, LH e FSH, podendo co-secretar dois ou mais hormônios) e clinicamente não secretores ou "não funcionantes". O diagnóstico é feito pelo fenótipo da hipersecreção (acromegalia, Cushing etc.) e, nos macroadenomas com efeito de massa, por hipopituitarismo e/ou distúrbios neurológicos, onde predominam as queixas visuais e cefaléia. Quanto aos mecanismos de tumorigênese hipofisária, a disputa entre causa primária hipotalâmica versus hipofisária ganhou força a favor da segunda graças às evidências da monoclonalidade dos tumores, juntamente com outros argumentos como a ausência de tecido hiperplásico circundando o adenoma cirurgicamente removido e a relativa independência do controle hipotalâmico. No entanto, admite-se que um papel permissivo do hipotálamo é importante para a progressão tumoral. Muitos mecanismos moleculares envolvidos na tumorigenese hipofisária já foram desvendados, incluindo oncogenes, genes supressores tumorais e fatores de crescimento, e serão descritos neste artigo de revisão.
Incidentalomas hipofisários
Authors: Vilar Lucio , Azevedo Monalisa F. , Barisic Gilka , Naves Luciana A.
Published: February 2006

Lesões hipofisárias clinicamente inaparentes são demonstradas através da ressonância magnética em aproximadamente 10% da população geral adulta, caracterizando os chamados incidentalomas hipofisários. A história natural dessas lesões ainda não está completamente estabelecida. Embora sejam tipicamente pequenos (< 10mm no seu maior diâmetro) e clinicamente silenciosos, alguns incidentalomas hipofisários podem secretar hormônios ou causar efeitos de massa por compressão sobre estruturas vizinhas. Além disso, uma minoria dessas lesões, principalmente aquelas com mais de 10mm (macroincidentalomas) podem crescer com o tempo; assim, o seguimento a longo prazo se faz necessário. Intervenções terapêuticas estão indicadas para os incidentalomas funcionantes (uso de agonistas dopaminérgicos ou ressecção transesfenoidal) ou para aqueles que causem efeitos de massa ou aumentem de tamanho durante o seguimento (ressecção transesfenoidal). Significante extensão supra-selar ou hipopituitarismo podem ser indicações adicionais para o tratamento cirúrgico, mesmo na ausência de compressão quiasmática.
Tumores não hipofisários da região selar
Authors: Czepielewski Mauro A. , Rollin Guilherme A.F.S. , Casagrande Alessandra , Ferreira Marcelo Paglioli , Ferreira Nelson P.
Published: February 2006

A hipófise, a sela túrcica e a região peri-selar podem ser acometidas por uma série de lesões, incluindo tumores benignos e malignos, bem como uma ampla variedade de doenças não neoplásicas. Os aspectos clínicos e radiológicos podem auxiliar no diagnóstico diferencial destas lesões. Porém, em muitos casos, somente a análise histopatológica pode estabelecer o diagnóstico definitivo. Neste artigo, revisamos principais tumores não hipofisários da região selar e peri-selar, ressaltando seus aspectos endócrinos mais relevantes.
Pathogenesis of differentiated thyroid cancer (papillary and follicular)
Authors: Maciel Rui M.B. , Kimura Edna T. , Cerutti Janete M.
Published: February 2006

Differentiated thyroid cancers (papillary - PTC and follicular - FTC) are the most common endocrine malignancies. The recent progresses in the understanding of PTC and FTC pathogenesis are summarized in this review. In PTC, a single mutation of BRAF (the gene for the B-type Raf kinase) (V600E) is responsible for the disease in 40-50% of patients, especially in older people and is associated with a poorer clinicopathological outcome. Due to these characteristics, its use as a specific diagnostic and prognostic marker for PTC in cytological specimens is being implemented. Another important cause of PTC is rearrangements of the RET tyrosine kinase receptor (RET/PTC), which represent a recombination of the promoter and N-terminal domain of a partner gene with the C-terminal region of the RET gene, resulting in a chimeric gene with a protein product containing a constitutively activated RET tyrosine kinase, responsible for 20-30% patients, specially the younger or after radiation. The pathogenesis of FTC is less understood. A chromosomal translocation between the transcription factor PAX8 and the peroxisome proliferator-activated receptorgamma (PPARgamma) occurs in 30-50% of patients; however, the presence of PAX8-PPARgamma is also demonstrated in follicular adenomas. Therefore, there is no complete evidence that PAX8-PPARgamma is the cause of FTC. Another finding in FTC is mutations on the RAS gene, which excludes PAX8-PPARgamma rearrangements. Several genes, as TRgamma, PTEN, PKAR1A, DDIT3, ARG2, ITM1 and C1orf24 - some discovered by techniques of differential gene expression -, have been recently implicated in the pathogenesis of FTC.
Carcinoma de tireóide pouco diferenciado: novas considerações terapêuticas
Authors: Graf Hans
Published: February 2006

Para a maioria dos carcinomas diferenciados de tireóide, como o papilífero e o folicular, após a tireoidectomia total e 131I para ablação de remanescentes tireoideanos, o tratamento com hormônios tireoideanos para suprimir os níveis de TSH reduz o crescimento de qualquer célula cancerosa remanescente, e o tratamento com radiação específica para as células cancerosas cura ou controla muito bem a doença. Os carcinomas de tireóide são considerados pouco diferenciados quando começam a perder as funções de captação de iodo e a dependência do TSH para crescimento e produção de proteínas tireóide-específicas, como proteína NIS, tireoglobulina e desiodases. Um dos maiores desafios no manejo de pacientes com carcinoma de tireóide derivados das células foliculares é o tratamento de tumores que evoluem apesar da cirurgia, 131I e supressão do TSH com T4. Com o melhor conhecimento da sinalização molecular anormal nas células tireoideanas cancerosas, atualmente novas terapias dirigidas a alvos moleculares específicos envolvidos na transformação neoplásica têm sido utilizadas. Com a identificação das necessidades moleculares críticas para a iniciação, manutenção e progressão tumoral, terapias combinadas com agentes terapêuticos alvo-dirigidos, agindo em cada uma destas etapas, irão melhorar o tratamento do carcinoma pouco diferenciado de tireóide.
Tratamento do tumor do córtex adrenal na infância
Authors: Pereira Rosana Marques , Michalkiewicz Edson , Pianovski Mara Albonei , França Susana Nesi , Boguszewski Margaret C.S. , Cat Izrail , Lacerda Filho Luiz de , Sandrini Romolo
Published: February 2006

O tumor do córtex adrenal (TCA) na infância é raro. Entretanto, no Paraná sua incidência é 15 vezes maior do que a observada em outros países. A mutação germinativa R337H TP53, presente em mais de 95% dos nossos pacientes, provavelmente está relacionada à maior incidência. Cento e vinte e cinco pacientes foram tratados no período de 1966 a 2003. A cirurgia é o único tratamento curativo. Em nossa experiência, tumores no estádio I, ausência de spillage durante a cirurgia e ausência de trombo são parâmetros relacionados à maior sobrevida. Dados preliminares mostram que a associação de etoposídeo, doxorrubicina, cisplatina e mitotano produziu remissão completa do tumor e/ou das metástases em alguns pacientes. Os efeitos colaterais destas drogas são comuns e pode ocorrer insuficiência adrenocortical. As doses de reposição de glicocorticóides e mineralocorticóides devem ser 2 a 3 vezes maiores que as doses fisiológicas.
Avanços recentes no conhecimento dos mecanismos moleculares envolvidos na tumorigênese adrenocortical
Authors: Lerario Antonio Marcondes , Mendonça Berenice B. de , Lin Chin Jia
Published: February 2006

A tumorigênese adrenal é um fenômeno complexo, que envolve múltiplas alterações genéticas. Uma melhor compreensão dos mecanismos que levam ao desenvolvimento dos tumores adrenocorticais possibilitaria não só a identificação precoce dos casos de má evolução, mas também o desenvolvimento de novas estratégias terapêuticas. Embora nos últimos anos tenham surgido vários estudos sobre a tumorigênese adrenocortical, o processo permanece em grande parte desconhecido. A maior parte dos trabalhos disponíveis estudou apenas um ou poucos genes. Por se tratar de um fenômeno complexo, técnicas que avaliam múltiplos, como os microarrays, possivelmente possibilitarão o entendimento de aspectos que até o momento são desconhecidos. Nesta revisão, tentamos resumir de forma abrangente os principais trabalhos científicos produzidos nos últimos anos a respeito do processo de tumorigênese adrenocortical.
Prevalência de lesão adrenal incidental em pacientes submetidos a tomografia computadorizada de tórax e abdome em um hospital geral brasileiro
Authors: Ferreira Eleci V. , Czepielewski Mauro A. , Faccin Carlos Sasso , Accordi Melissa Coral , Furtado Álvaro Porto Alegre
Published: February 2006

INTRODUÇÃO: Determinar prospectivamente a prevalência de lesão adrenal incidental a tomografia computadorizada (TC) em um hospital geral universitário brasileiro. PACIENTES E MÉTODO: Estudo transversal, prospectivo, avaliando pacientes consecutivos sem doença adrenal conhecida, submetidos a TC de tórax e abdome no Hospital de Clínicas de Porto Alegre, em um período de 10 meses. Incidentalomas adrenais foram definidos pela presença de alteração no contorno, tamanho ou densidade da glândula. Valores de kappa foram calculados, avaliando a concordância intra e inter-observador. RESULTADOS: Identificaram-se 101 lesões adrenais incidentais em 83 de 3.382 pacientes, correspondendo a uma prevalência de 2,5% (IC 95%: 1,0%-3,2%). A prevalência de lesões adrenais aumentou com a idade e foi significativamente mais alta em pacientes do sexo masculino (3,3% vs. 1,5%; p= 0,01). Na avaliação das concordâncias intra e inter-observador, obteve-se um kappa de 0,76 (boa concordância) e 0,83 (excelente concordância) respectivamente. CONCLUSÕES: A prevalência de incidentaloma adrenal detectada por TC foi semelhante à de diversas séries clínicas retrospectivas publicadas. Os dois fatores que influenciaram de forma independente a distribuição dos incidentalomas foram aumento na idade e sexo masculino.
Tumores endócrinos associados às mutações das proteínas Gsalfa e Gi2alfa
Authors: Bezerra Milena Gurgel Teles , Latronico Ana Claudia , Fragoso Maria Candida B.V.
Published: February 2006

Diversas mutações em oncogenes promovem o crescimento tumoral através da indução de atividade de proteínas que normalmente transmitem sinais proliferativos a partir de fatores extracelulares. As proteínas G são uma família de proteínas ligadas ao nucleotídeo guanina que apresentam homologia estrutural e estão amplamente distribuídas em células eucariotas. Elas são constituídas por três sub-unidades (alfa, beta e gama). A sub-unidade alfa apresenta o sítio de ligação ao nucleotídeo guanina e é única para cada proteína G. A proteínas G estão acopladas aos receptores de superfície celular com sete hélices transmembrana com uma grande variedade de efetores intracelulares e segundos mensageiros. Um subgrupo de tumores endócrinos, incluindo os tumores hipofisários secretores de GH e ACTH, nódulos tireoideanos autônomos, tumores adrenocorticais e gonadais, foram associados a mutações somáticas ativadoras em códons altamente conservados das proteínas Gs (Arg201 e Gln227) e Gi (Arg179, Gln205). Estes achados moleculares indicaram que as proteínas G atuam como oncogenes, contribuindo no processo da tumorigênese endócrina em humanos.
Octreotide-LAR + adrenalectomia bilateral no manejo de tumores carcinóides produtores de ACTH
Authors: Czepielewski Mauro A. , Colli Maikel , Harlos Tatiana , Silveiro Sandra Pinho , Maraschin Jorge , Copette Fabio , Leitão Cristiane B. , Rollin Guilherme A.F.S.
Published: February 2006

A síndrome de Cushing (SC) por ACTH ectópico é um distúrbio com alta morbi/mortalidade, cujo manejo necessita de medidas terapêuticas rápidas e eficientes. Os tumores carcinóides produtores de ACTH (TuCA-ACTH) apresentam quadro ainda mais grave em decorrência dos distúrbios associados à síndrome carcinóide (SCA) que acentuam as repercussões do hipercortisolismo. Assim, o manejo de pacientes com TuCA-ACTH deve incluir o controle do hipercortisolismo e do distúrbio carcinóide, sendo escassas informações que abordam tais estratégias. Relatamos 3 pacientes (2F, 1M) com TuCA-ACTH (2 pancreáticos e 1 oculto) que apresentavam manifestações clínicas de SC (n= 3) e SCA (n= 2): 2 foram investigados inicialmente por apresentarem SC e um, SCA. Em todos ocorreu hipocalemia espontânea, hipertensão arterial e diabetes mellitus, sendo demonstrada a presença de hipercortisolismo severo e elevação de ACTH. A administração de octreotide-LAR reduziu os níveis de ACTH de 230.000 para 30.000pg/ml no caso 1, e controlou os sintomas da SCA e das lesões neoplásicas no caso 2, enquanto o octreotide subcutâneo controlou a SCA e reduziu parcialmente os sintomas do hipercortisolismo no caso 3. Os 3 pacientes foram adrenalectomizados bilateralmente, medida essencial para o controle da SC (desaparecimento da hipocalemia, miopatia, hipertensão arterial e diabetes mellitus). Nossos dados demonstram que a associação destas estratégias, em conjunto com terapias anti-neoplásicas, pode contribuir para estabilização e/ou controle definitivo dos TuCA-ACTH.
Biologia molecular das neoplasias de próstata
Authors: Brum Ilma Simoni , Spritzer Poli Mara , Brentani Maria Mitzi
Published: February 2006

O câncer de próstata (CP) é uma das principais causas de doença e morte, representando no Brasil a segunda causa de óbitos por câncer em homens. A hiperplasia prostática benigna (HPB) é uma doença progressiva de alta prevalência, com evidências histológicas em 50% dos homens aos 50 anos e 90% aos 80 anos de idade. A patogênese das neoplasias prostáticas tem sido associada à ação dos androgênios e a seu receptor nuclear específico, embora os mecanismos moleculares que envolvem os processos de proliferação, diferenciação e apoptose não estejam bem estabelecidos, assim como os mecanismos de transformação neoplásica e carcinogênese. Co-ativadores e co-repressores podem também contribuir para a carcinogênese prostática, ligando-se diretamente aos receptores nucleares, recrutando proteínas adicionais e interagindo com a maquinaria transcricional para aumentar a transcrição de genes-alvo. Polimorfismos do receptor de androgênios e da 5alfa redutase tipo 2 foram identificados e poderiam estar associados com risco para CP. Genes reguladores do ciclo celular e da apoptose, bem como fatores de crescimento, também participam de processos relacionados com a tumorigênese prostática. Assim, alterações no padrão da expressão gênica do tecido normal podem levar ao desenvolvimento do fenótipo maligno e potencialmente estes genes podem servir como marcadores de prognóstico. Com o advento de novas tecnologias moleculares, o número de genes marcadores potenciais para o CP cresce dia a dia, mas os dados atuais requerem ainda validação com maior número de amostras e correlação com o processo da doença. Trazê-los do ambiente de laboratório para o uso clínico requer uma análise rigorosa e há, portanto, um longo caminho ainda a percorrer.
Neoplasias associadas à síndrome dos ovários policísticos
Authors: Spritzer Poli Mara , Morsch Débora Martinho , Wiltgen Denusa
Published: February 2006

A síndrome dos ovários policísticos (PCOS) é a endocrinopatia mais comum em mulheres em idade reprodutiva, caracterizada pela presença de anovulação, infertilidade e hiperandrogenismo, e freqüentemente associada à obesidade e resistência insulínica. Postula-se que, a longo prazo, estas pacientes possam apresentar maior risco de neoplasias do trato reprodutivo como carcinoma (CA) de endométrio, mama e ovário. Um risco aumentado de hiperplasia e CA endometrial nessas pacientes tem sido demonstrado em vários estudos, embora seja reconhecido que a variabilidade dos critérios de seleção para o diagnóstico de PCOS em alguns destes estudos limite o valor dos dados. Apesar das pacientes com PCOS apresentarem características clínicas associadas com um aumento de risco de CA de mama, até o momento não foi possível relacionar com certeza a presença da síndrome per se com maior prevalência desta neoplasia. Finalmente, quanto ao CA do ovário, considera-se que altas concentrações locais de hormônios esteróides e fatores de crescimento representam fatores de risco para esta neoplasia. Apesar destas alterações serem comumente observadas nas pacientes PCOS não tratadas ou em tratamento para infertilidade, ainda são poucos os estudos que avaliam uma possível relação entre PCOS e CA de ovário, mas seus resultados, embora conflitantes, sugerem ausência de associação.
Carcinoma de paratiróide
Authors: Vieira José Gilberto H. , Ohe Monique N. , Hauache Omar M. , Oliveira Ulisses Maia de , Delana Janaina Martins , Gonçalves André , Lazaretti-Castro Marise
Published: February 2006

Carcinoma de paratiróide é uma condição rara, correspondendo na maior parte das casuísticas a menos de 1% dos casos de hiperparatiroidismo primário (HPP). No entanto, pela sua gravidade, e com o prognóstico dependente do diagnóstico precoce e de uma conduta agressiva, é fundamental que a suspeita clínica seja feita pré-operatoriamente. As características clínicas são compatíveis com um caso de HPP grave, sintomático, com tumor cervical >1,5cm, podendo ser palpável. A definição anátomo-patológica pode ser difícil em muitos casos. Nossa casuística (1983-2004) compreende 7 casos, todos sintomáticos, com síndrome hipercalcêmica e doença óssea presente na maioria. Em 6/7 o tumor era palpável, e todos apresentavam quadro bioquímico compatível. Três pacientes faleceram em quadro de hipercalcemia refratária. Dados recentes apontam para uma mutação no gene HRPT2 como base molecular para o desenvolvimento destes tumores. A conduta é cirúrgica e deve incluir hemitiroidectomia e exploração cervical ampliada, procurando focos metastáticos. O pós-operatório é compatível com a gravidade da alteração metabólica pré-existente, sendo comum a tendência a hipocalcemia. O prognóstico de longo prazo depende do diagnóstico precoce, do sucesso cirúrgico e do controle da hipercalcemia. Novas possibilidades terapêuticas, na forma de bisfosfonatos e drogas calcimiméticas, bem como a possibilidade de diagnóstico genético, tendem a melhorar o prognóstico desta grave condição.
Acromegalia e doença tiroideana: prevalência de câncer de tireóide
Authors: Marchisotti Frederico G. , Umeda Luciana Mela , Zach Patrícia Lins , Saldanha Michelle D. D. , First Olga Simoni Nobel , Liberman Bernardo
Published: February 2006

A relação entre câncer e acromegalia tem sido objeto de estudo há muitos anos. A partir de um caso de carcinoma diferenciado de tireóide em um de nossos pacientes acromegálicos, estudamos uma série de 100 outros acromegálicos e encontramos dois outros casos de câncer de tireóide, descritos neste trabalho. A partir daí, levantamos os dados da literatura sobre esta última associação e sua possível patogênese. A prevalência de patologias tireoidianas é aumentada dentre os acromegálicos, às custas, principalmente, do bócio nodular. Esta associação será abordada, assim como a relação entre o fator de crescimento insulina símile I (IGF-I) e câncer, numa tentativa de entender melhor seu significado frente aos nossos casos. Nós concluímos que seria prudente realizar exame ultrassonográfico periódico em acromegálicos, seguido de Punção Aspirativa com Agulha Fina (PAAF) dos nódulos suspeitos.
Carcinoid syndrome: diagnosis and medical management
Authors: van der Lely Aart J. , Herder Wouter W. de
Published: February 2006

Gastro-intestinal carcinoids are slow growing tumors arising from enterochromaffin or Kulchitsky cells. Their clinical presentation depends on what combination of bioactive substances is secreted. Midgut carcinoid can present with the carcinoid syndrome in the presence of liver metastases. Its most typical clinical manifestations include cutaneous flushing and diarrhea. A nonspecific biochemical tumor marker for carcinoid tumors is serum chromogranin A and a specific marker for the carcinoid syndrome is the increased urinary excretion of 5-hydroxy indole acetic acid (5-HIAA). Localizing studies in carcinoid tumors/syndrome are: transabdominal ultrasonography (US), endoscopy, endoscopic US, videocapsule endoscopy, computerized tomography, magnetic resonance imaging, selective abdominal angiography, 111In-pentetreotide scintigraphy (and intraoperative radionuclide probe), 123I (131I)-metaiodobenzylguanidine (MIBG) scintigraphy, bone scintigraphy and 11C-5-HT positron emission tomography (PET). Therapies for carcinoid tumors/syndrome are: surgery, somatostatin analogs, interferon-alpha, radiotherapy, liver dearterialization, liver (chemo, or radio)-embolization, alcohol sclerotherapy of liver metastases, radiofrequency ablation of liver metastases, cryosurgery of liver metastases, occasionally liver transplantation, radiotherapy-coupled somatostatin analogs, 131I-MIBG and occasionally chemotherapy.
Endoscopic ultrasound versus endoscopic retrograde cholangiography for the diagnosis of choledocholithiasis: the influence of the size of the stone and diameter of the common bile duct
Authors: Ney Marcus Vinicius Silva , Maluf-Filho Fauze , Sakai Paulo , Zilberstein Bruno , Gama-Rodrigues Joaquim , Rosa Heitor
Published: February 2006

BACKGROUND: Endoscopic retrograde cholangiography is highly accurate in diagnosing choledocholithiasis, but it is the most invasive of the available methods. Endoscopic ultrasonography is a very accurate test for the diagnosis of choledocholithiasis with a risk of complications similar to that of upper gastrointestinal endoscopy. AIM: To compare the accuracy of endoscopic ultrassonography and endoscopic retrograde cholangiography in the diagnosis of common bile duct stones before laparoscopic cholecystectomy and to analyze endoscopic ultrasound results according to stone size and common bile duct diameter. PATIENTS AND METHODS: Two hundred and fifteen patients with symptomatic gallstones were admitted for laparoscopic cholecystectomy. Sixty-eight of them (31.7%) had a dilated common bile duct and/or hepatic biochemical parameter abnormalities. They were submitted to endoscopic ultrassonography and endoscopic retrograde cholangiography. Sphincterotomy and sweeping of the common bile duct were performed if endoscopic ultrassonography or endoscopic retrograde cholangiography were considered positive for choledocholithiasis. After sphincterotomy and common bile duct clearance the largest stone was retrieved for measurement. Endoscopic or surgical explorations of the common bile duct were considered the gold-standard methods for the diagnosis of choledocholithiasis. RESULTS: All 68 patients were submitted to laparoscopic cholecystectomy with intraoperative cholangiography with confirmation of the presence of gallstones. Endoscopic ultrassonography was a more sensitivity test than endoscopic retrograde cholangiography (97% vs. 67%) for the detection of choledocholithiasis. When stones >4.0 mm were analyzed, endoscopic ultrassonography and endoscopic retrograde cholangiography presented similar results (96% vs. 90%). Neither the size of the stone nor the common bile duct diameter had influence on endoscopic ultrasonographic performance. CONCLUSIONS: For a group of patients with an intermediate or moderate risk with respect to the likelihood of having common bile duct stones, endoscopic ultrassonography is a better test for the diagnosis of choledocholithiasis when compared to endoscopic retrograde cholangiography mainly for small-sized calculi.
Ligadura de ducto biliar como modelo de estudo da síndrome hepatopulmonar e estresse oxidativo
Authors: Tieppo Juliana , Vercelino Rafael , Dias Alexandre Simões , Marroni Cláudio Augusto , Marroni Norma
Published: February 2006

RACIONAL: A síndrome hepatopulmonar é caracterizada por uma disfunção hepática e pela existência de dilatações dos vasos pulmonares, levando a alterações nas trocas gasosas, tendo algumas das suas características observadas de forma experimental no modelo de ligadura de ducto biliar. OBJETIVOS: Avaliar o estresse oxidativo no tecido pulmonar de ratos cirróticos por ligadura de ducto biliar comum. MATERIAIS E MÉTODOS: Foram utilizados 12 ratos machos Wistar, pesando entre 200 e 300 g, divididos em dois grupos: controles (Co = 6) e cirróticos (Ci = 6). Foram realizadas avaliações de transaminases, gasometria arterial, avaliação da lipoperoxidação (substâncias reativas ao ácido tiobarbitúrico e quimiluminescência) e quantificação da atividade enzimática antioxidante através das concentrações da enzima superóxido dismutase. Os tecidos analisados para avaliação da síndrome hepatopulmonar foram o fígado cirrótico e o pulmão. RESULTADOS: Os animais com ligadura de ducto biliar apresentaram alteração nas transaminases: aspartato aminotransferase, Co = 105,3 ± 43/Ci = 500,5 ± 90,3 alanina aminotransferase, Co = 78,75 ± 37,7/Ci = 162,75 ± 35,4 e fosfatase alcalina, Co = 160 ± 20,45/Ci = 373,25 ± 45,44. Em relação à lipoperoxidação e à resposta antioxidante, estas também apresentaram diferenças estatisticamente significativas quando avaliadas no pulmão (substâncias reativas ao ácido tiobarbitúrico) Co = 0,87 ± 0,3/Ci = 2,01 ± 0,9; quimiluminescência Co = 16008,41 ± 1171,45/Ci = 20250,36 ± 827,82; superóxido dismutase Co = 6,66 ± 1,34/Ci = 16,06 ± 2,67. CONCLUSÕES: Os dados obtidos sugerem que no modelo experimental de cirrose por ligadura de ducto biliar há aumento significativo da lipoperoxidação no tecido pulmonar, bem como aumento na atividade da enzima antioxidante superóxido dismutase, sugerindo a presença de dano pulmonar decorrente da cirrose biliar secundária.