Anaplastic Thyroid Carcinoma Morphologic Findings and PAX-8 Expression in Cytology Specimens

Objective To evaluate the morphologic findings most encountered in anaplastic thyroid carcinomas (ATCs) and evaluate for the expression of PAX-8. Study Design The cytology specimens from 21 cases of ATC were evaluated for the following several cytologic criteria, cell morphology, pleomorphism, presence or absence of multinucleated cells, neutrophilic infiltrate and well-differentiated component. Immunohistochemical studies for PAX-8 were performed on cell blocks in selected cases. Results The most common morphology present was epithelioid, followed by spindle, multinucleated giant cell and rhabdoid, with 75% demonstrating more than 1 cell morphology. Marked pleomorphism (81%), neutrophilic infiltrate (90%) and necrosis (63%) were frequent. No nuclear grooves, colloid or well-differentiated component was idenrifled in any case. Immunocytochemical stains for PAX-8 were negative in 5 cases in which a cell block was available. Conclusion ATC is a tumor with diverse morphologic characteristics, and more than 1 cell morphology is usually present A neutrophilic infiltrate is a common finding and represents a clue to the correct diagnosis. (Acta Cytol 2010;54:668-672)

Genética molecular do hipotireoidismo congênito

O hipotireoidismo congênito (HC) ocorre, mundialmente, em 1/3000-4000 neonatos e pode ser classificado em permanente ou transitório. O HC primário é responsável pela maioria dos afetados, enquanto o secundário e terciário são raros. Nos países iodo-suficientes, a disgenesia tireóidea (DT) é a causa mais freqüente de HC. Os defeitos hereditários da síntese hormonal ocorrem em minoria de crianças portadoras de HC. Fatores ambientais, genéticos e auto-imunes concorrem na etiologia do HC, mas na maioria dos casos de DT a causa é obscura. Atribui-se aos genes envolvidos na ontogenia da glândula tireóidea, como os fatores de transcrição TITF1, TITF2, PAX-8 e receptor de TSH (TSHR), função patogenética na DT. Até o momento não foi descrita anormalidade no gene TITF1 como causa de HC, enquanto foram identificadas mutações no PAX-8 em cinco recém-nascidos com DT. Embora não envolvidas na DT, mutações inativadoras do TSHR podem produzir espectro de defeitos congênitos oscilando entre hipertirotropinemia com eutireoidismo e hipotireoidismo com hipoplasia glandular. A clonagem dos genes envolvidos na biossíntese dos hormônios tireóideos, como o da tireoperoxidase (TPO) e tireoglobulina (Tg), permitiu a identificação de mutações responsáveis por alguns casos de bócio e hipotireoidismo decorrente de defeito de incorporação de iodeto ou anormalidades na síntese de Tg. Recentemente, foi demonstrada a base molecular do defeito de transporte ativo de iodeto e da síndrome de Pendred, respectivamente, devidas a mutações no gene NIS (simportador de sódio e iodeto) e no gene PDS (pendrina). em conclusão, grande parte dos pacientes com HC e DT não tem esclarecida, ainda, a causa molecular desta síndrome.

Aspectos genéticos do hipotireoidismo congênito

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

1.° Tractatus pacis inter Ludovicum IX. Regem Francorum, et Henricum III. Regem Angliae : anno 1259. — 2.° Tractatus pacis inter Philippum III. Regem Francorum, et Edwardum I. Regem Angliae : anno 1279. — 3.° Tractatus pacis inter eosdem Reges : anno 1286. — 4.° Quarta et ultima pax facta inter Reges : anno 1303. translata de romancio in latinum, de verbo ad verbum. — 5.° Alia concordantia, seu compositio vel pax inter Reges : anno 1303. — 6.° Pronunciatio Bonifacii, Papae, super pacibus : anno pontificatus quarto. — 7.° De remediis Aquitanorum adversùs vexationem curiae Regis Franciae. — 8.° Copia arresti contra Arnaldum de Romynhano, dati anno 1312. — 9.° Variae litterae Philippi Pulchri et Ludovici X. de rebus Anglicis. — 10.° Bulla Clementis, Papae V. approbans donationem Motae et domorum de Pessaco, factam ecclesiae Burdegalensi à nobili viro Gaillardo de Guto, germano suo, anno primo pontificatus. — 11.° Traitté de paix conclu entre les Rois Philippe et Edouard ; sans date. — 12.° Lettres de Charles IV. Roy de France et de Navarre, touchant les excès commis au lieu de Saint-Sacerdos par le Senechal de Gascogne : l'an 1324. — 13.° Traitté entre la France et l'Angleterre : en la même année. — 14.° Judicium latum apud Oleronem, anno 1287. per D. Norwicensem Episcopum, contra D. Joannem de Greilliaco, dudum Senescallum Vasconiae. — 15.° Tractatus matrimonii inter Alienoram filiam Edwardi Regis Angliae, et Alphonsum filium majorem Petri Regis Aragonum. — 16.° Litterae Petri, Regis Aragonum, de matrimonio filii sui Alphonsi cum Alienora, filia primogenita Regis Edwardi. — 17.° Joannis XXII. bulla contra Michaëlem de Cesena, Ministrum generalem ordinis Minorum : VIII. idus Junii, pontificatus anno XII. — 18.° Edwardi, Regis Anglorum, constitutiones variae ad Aquitaniam spectantes et ad Angliam. — 19.° Traitté de paix entre les Rois de France et d'Angleterre, fait en l'an 1325. — 20.° Litterae Agennensium ad Carolum IV. Regem Franciae, pro Rege Angliae, nominatim de facto Sancti-Sacerdotis, scriptae anno 1324. — 21.° Tractatus matrimonii inter Alphonsum, Regem Castellae et Legionis, et Alienoram, filiam Edwardi Regis Angliae ; item alius inter Edwardum, Regis Angliae primogenitum, et Alienoram sororem Regis Castellae : anno 1325. — 22.° Instructions données par le Roy d'Angleterre à ses Ambassadeurs allans en Espagne pour le fait dudit mariage. — 23.° Abusiones quae exercentur in regno Angliae circa beneficia ecclesiastica ; et remedia sine quibus nunquam cessare creduntur. — 24.° Clementis V. bulla de saecularisatione monasterii de sancto Aemiliano, in dioecesi Burdigalensi ; data anno pontificatus quinto. — 25.° Litterae Edwardi II. Regis Angliae, de servanda pace facta cum Carolo IV. Rege Franciae. — 26.° Ejusdem litterae quibus Edmundum, Comitem Cantiae, fratrem suum, constituit Capitaneum in Ducatu Aquitaniae. — 27.° Lettres de Charles IV. Roy de France, contre le Roy d'Angleterre, qui refusoit de luy faire les foy et hommage pour la Duché d'Aquitaine : de l'année 1324. — 28.° Litterae ejusdem Caroli IV. Regis Francorum, de eadem re ; quibus Carolo, Comiti Valesiae, patruo suo, dat potestatem puniendi rebelles Aquitaniae ; datae anno 1324. — 29.° Litterae ejusdem de salvagardia Guillelmi Galteri, Clerici, datae anno 1323. — 30.° Ejusdem litterae pro Margareta de Guouda, tutrice Pontii domini de Castellione, filii sui, datae anno 1323. — 31.° Ejusdem litterae pro Comitissa Fuxi et Vicecomitissa Bearni et Marciani, tutrice Gastonis filii sui ; datae anno 1322. — 32.° Litterae Antonini Pessaigne, Senescalli Ducatus Aquitaniae, quibus Ostencium Jordani, Clericum ac Jurisperitum, constituit suum et Regis Angliae Procuratorem ; datae anno 1318. — 33.° Litterae Almarici domini de Credonio, Senescalli Ducatus Aquitaniae, quibus Roberto de la Vertadausa, Anglico, decem libras Turonensium parvorum singulis annis solvendas concedit vice et nomine Regis Angliae ; datae anno 1322. — 34.° Divers actes entre les Rois de France et d'Angleterre, pour assurer la paix ; faits depuis l'an 1259. jusques en 1323. — 35.° Acta processus habiti in curia Romana inter capitulum ecclesiae Coventrensis et capitulum ecclesiae Lichefeldiensis de electione Episcopi, tempore Joannis XXII. — 36.° Traitté d'alliance et de confederation entre la France et l'Ecosse contre l'Angleterre ; fait en 1325. — 37.° Articuli exhibiti à Procuratore ecclesiae Lichfeldensis. — 38.° Articuli exhibiti à Procuratore ecclesiae Coventrensis. — 39.° Joannis XXII. bulla de unione Episcopatuum Corkagiensis et Clonensis, data Avenione anno pontificatus XI. — 40.° Acta processus apud eumdem Papam agitati super praebenda sancti Stephani in ecclesia Beverlacensi.

Colbertinus

Revisão taxonômica de Croton sect. Lamprocroton (Müll. Arg.) Pax (Euphorbiaceae s.s.)

Croton is the second bigger and more diverse genus in the family Euphorbiaceae, with about 1,200 species distributed in 40 sections, occurring in all tropical areas, most of them in Americas. In South America, Brazil is the country in which a larger number of taxa are found, ca. 356. According to recent classification, the genus belongs to the tribe Crotoneae, and despite the wide and morphological diversity, it would be a monophyletic taxon. However, a phylogenetic analysis using markers of ITS region from nuclear ribosomal DNA, and of trnL-F from plastidial DNA, showed that Croton, like traditionally circumscribed, is not a monophyletic taxon. A taxonomic revision of Croton section Lamprocroton (Müll. Arg.) Pax is presented here. It is a Neotropical group with most of its species occurring from Southeast and South Brazil to southern South America (Uruguay and Argentina). Morphologically, the members of Lamprocroton are characterized as monoecious or dioecious shrubs or subshrubs, with a lepidote indumentum at least in part of foliage, entire leaves with no glands. The staminate flowers have 9 to 16 stamens and the pistillate flowers may have equal or unequal sepals, reduced to absent petals, and styles once or twice bifid. Overall, are recognized 26 species in the group, three of them new to the science. Identification key, morphological descriptions, illustrations, phenological period, as well as data on geographic distribution and general comments of each species are presented. Four taxa were excluded from C. sect. Lamprocroton because they do not show the morphological features that are diagnostics of the section. Four species that are poorly known were not included in the taxonomic treatment.

Pax : los operarios de Astorga : memoria agradecida

Expone la labor docente y ministerial de dos presb??teros diocesanos de Astorga. Han recibido m??ltiples reconocimientos por su labor a la cultura leonesa y defensa en??rgica del patrimonio eclesi??stico as?? como de las tradiciones de la ciudad astorgana as?? como de su di??cesis.

Jornada europea de estudios de 'Pax Romana'.

Análisis de las acontecido en la Jornada europea de estudios de 'Pax Romana' celebrada durante el mes de abril de 1952 en Salzburgo, Austria, organizada por el Movimiento Internacional de Intelectuales Católicos de 'Pax romana', sobre el tema: 'Los derechos de los padres en relación con la escuela'. Algunas de las conclusiones a las que se llegaron, se resumen en los siguientes puntos: 1. El niño tiene derecho a una educación completa, al desarrollo integral de su personalidad. 2. La familia tiene el derecho y deber de llevar a cabo la procreación. 3. La Iglesia debe llevar a cabo las obras del bautismo, la educación moral y religiosa. 4. El Estado debe proteger los derechos del niño; promover la instrucción y educación y velar sobre la escuela. 5. La escuela tiene derecho a la libertad necesaria para el desarrollo de su existencia y libre ejercicio de su función. 6. La escuela no oficial tiene el derecho de representación sobre temas relacionados con ella. 7. La familia tiene el derecho de poder escoger entre la escuela oficial y la privada. 8. La familia tiene derecho a exigir una equitativa distribución de los fondos públicos, cualquiera que sea la escuela que frecuenten sus hijos.

Pax gene expression in the developing central nervous system of Ciona intestinalis

We compare the expression patterns in Ciona intestinalis of three members of the Pax gene family, CiPax3/7, CiPax6 and Cipax2/5/8. All three genes are expressed in restricted patterns in the developing central nervous system. At the tailbud stage, CiPax3/7 is present in three patches in the brain and along the posterior neural tube, CiPax6 throughout the anterior brain and along the posterior neural tube and CiPax2/5/8 in a restricted region of the posterior brain. Double in situ hybridisations were used to identify areas of overlap between the expression of different genes. This showed that CiPax3/7 overlaps with the boundaries of CiPax6 expression in the anterior brain, and with CiPax2/5/8 in the posterior brain. The overlap between CiPax3/7 and CiPax2/5/8 is unlike that described in the ascidian Halocynthia rorezti. (C) 2003 Elsevier B.V. All rights reserved.

Evolution of paired domains: Isolation and sequencing of jellyfish and hydra Pax genes related to Pax-5 and Pax-6

Pax proteins are a family of transcription factors with a highly conserved paired domain; many members also contain a paired-type homeodomain and/or an octapeptide. Nine mammalian Pax genes are known and classified into four subgroups: Pax-1/9, Pax-2/5/8, Pax-3/7, and Pax-4/6. Most of these genes are involved in nervous system development. In particular, Pax-6 is a key regulator that controls eye development in vertebrates and Drosophila. Although the Pax-4/6 subgroup seems to be more closely related to Pax-2/5/8 than to Pax-3/7 or Pax-1/9, its evolutionary origin is unknown. We therefore searched for a Pax-6 homolog and related genes in Cnidaria, which is the lowest phylum of animals that possess a nervous system and eyes. A sea nettle (a jellyfish) genomic library was constructed and two pax genes (Pax-A and -B) were isolated and partially sequenced. Surprisingly, unlike most known Pax genes, the paired box in these two genes contains no intron. In addition, the complete cDNA sequences of hydra Pax-A and -B were obtained. Hydra Pax-B contains both the homeodomain and the octapeptide, whereas hydra Pax-A contains neither. DNA binding assays showed that sea nettle Pax-A and -B and hydra Pax-A paired domains bound to a Pax-5/6 site and a Pax-5 site, although hydra Pax-B paired domain bound neither. An alignment of all available paired domain sequences revealed two highly conserved regions, which cover the DNA binding contact positions. Phylogenetic analysis showed that Pax-A and especially Pax-B were more closely related to Pax-2/5/8 and Pax-4/6 than to Pax-1/9 or Pax-3/7 and that the Pax genes can be classified into two supergroups: Pax-A/Pax-B/Pax-2/5/8/4/6 and Pax-1/9/3/7. From this analysis and the gene structure, we propose that modern Pax-4/6 and Pax-2/5/8 genes evolved from an ancestral gene similar to cnidarian Pax-B, having both the homeodomain and the octapeptide.

Synthesis And Antiproliferative Activity Of 8-hydroxyquinoline Derivatives Containing A 1,2,3-triazole Moiety.

Twelve novel 8-hydroxyquinoline derivatives were synthesized with good yields by performing copper-catalyzed Huisgen 1,3-dipolar cycloaddition (click reaction) between an 8-O-alkylated-quinoline containing a terminal alkyne and various aromatic or protected sugar azides. These compounds were evaluated in vitro for their antiproliferative activity on various cancer cell types. Protected sugar derivative 16 was the most active compound in the series, exhibiting potent antiproliferative activity and high selectivity toward ovarian cancer cells (OVCAR-03, GI50 < 0.25 μg mL(-1)); this derivative was more active than the reference drug doxorubicin (OVCAR-03, GI50 = 0.43 μg mL(-1)). In structure-activity relationship (SAR) studies, the physico-chemical parameters of the compounds were evaluated and docking calculations were performed for the α-glucosidase active site to predict the possible mechanism of action of this series of compounds.

Characterization Of A Protein-protein Interaction Network Of The Cbl-interacting Protein Kinase 8 From Sugarcane.

Plants are sessile organisms and have evolved to tolerate a constantly changing environment. After the onset of different stress conditions, calcineurin B-like (CBL) proteins can sense calcium signals and activate CBL-interacting protein kinase (CIPK) proteins, which can phosphorylate downstream proteins to reestablish plant homeostasis. Previous studies in the bioenergy crop sugarcane showed that the ScCIPK8 gene is induced by drought stress and is also related to sucrose content. Here, we have characterized the protein-protein interactions of ScCIPK8 with six CBL proteins (ScCBL1, ScCBL2, ScCBL3, ScCBL6, ScCBL9, and ScCBL10). Yeast two-hybrid assays showed that ScCIPK8 interacts with ScCBL1, ScCBL3, and ScCBL6. Bimolecular fluorescence complementation assays confirmed in planta the interactions that were observed in yeast cells. These findings give insights on the regulatory networks related to sugar accumulation and drought stress responses in sugarcane.

Antioxidative responses of cell suspension cultures of two Coffea arabica varieties to low aluminum levels at pH 5.8

The effects of aluminum (Al) on the activities of antioxidant enzymes and ferritin expression were studied in cell suspension cultures of two varieties of Coffea arabica, Mundo Novo and Icatu, in medium with pH at 5.8. The cells were incubated with 300 µM Al3+, and the Al speciation as Al3+ was 1.45% of the mole fraction. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) were increased in Mundo Novo, whereas glutathione reductase (GR) and guaiacol peroxidase (GPOX) activities remained unchanged. SOD, GR, and GST activities were increased in Icatu, while CAT activity was not changed, and GPOX activity decreased. The expression of two ferritin genes (CaFer1 and CaFer2) were analyzed by Real-Time PCR. Al caused a downregulation of CaFER1 expression and no changes of CaFER2 expression in both varieties. The Western blot showed no alteration in ferritin protein levels in Mundo Novo and a decrease in Icatu. The differential enzymes responses indicate that the response to Al is variety-dependent.

Long-term follow-up of an 8-year-old boy with insulinoma as the first manifestation of a familial form of multiple endocrine neoplasia type 1

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary cancer syndrome characterized mostly by parathyroid, enteropancreatic, and anterior pituitary tumors. We present a case of an 8-year-old boy referred because of hypoglycemic attacks. His diagnosis was pancreatic insulinoma. Paternal grandmother died due to repeated gastroduodenal ulcerations and a paternal aunt presented similar manifestations. At a first evaluation, the father presented only gastric ulceration but subsequently developed hyperparathyroidism and lung carcinoid tumor. During almost 15 years of follow-up, three brothers and the index case presented hyperparathyroidism and hyperprolactinemia. Molecular study showed a G to A substitution in intron 4, at nine nucleotides upstream of the splicing acceptor site, causing a splicing mutation. All affected members of the family have the same mutation. Paternal grandmother and aunt were not studied and the mother does not carry any mutation. MEN1 is a rare condition that requires permanent medical assistance. Early clinical and genetic identification of affected individuals is essential for their own surveillance and also for genetic counseling.

Pulp capping materials exert an effect on the secretion of IL-1β and IL-8 by migrating human neutrophils

Pulp repair is a complex process whose mechanisms are not yet fully understood. The first immune cells to reach the damaged pulp are neutrophils that play an important role in releasing cytokines and in phagocytosis. The objective of this study was to analyze the effect of different pulp-capping materials on the secretion of interleukin-1 beta (IL-1β) and interleukin-8 (IL-8) by migrating human neutrophils. Neutrophils were obtained from the blood of three healthy donors. The experimental groups were calcium hydroxide [Ca(OH)2], an adhesive system (Single Bond), and mineral trioxide aggregate (MTA). Untreated cells were used as control. Transwell chambers were used in performing the assays to mimic an in vivo situation of neutrophil chemotaxis. The pulp-capping materials were placed in the lower chamber and the human neutrophils, in the upper chamber. The cells were counted and the culture medium was assayed using ELISA kits for detecting and quantifying IL-1β and IL8. The data were compared by ANOVA followed by Tukey's test (p < 0.05). The secretion of IL-8 was significantly higher in all groups in comparison to the control group (p < 0.05). The adhesive system group showed higher IL-8 than the MTA group (p < 0.05). The secretion of IL-1β was significantly greater only in the MTA group (p < 0.001). It was concluded that only MTA is able to improve the secretion of IL-1β, and all materials tested increased IL-8 secretion. These results combined with all the other biological advantages of MTA indicate that it could be considered the material of choice for dental pulp capping.