No description available.

T cells play pivotal roles in the immune system and focused secretion of either cytokines or cytotoxic molecules toward its target is crucial for T cell functions. This directional secretion involves two critical steps: the movement of the microtubule organizing center (MTOC) up to the cell-cell contact site and the directed movement of secretory vesicles towards the MTOC. The minus end-directed microtubule motor protein dynein was previously shown in our studies and those of others to accumulate and anchor at the contact site where it then draws the MTOC up to the contact site. A variety of studies led to the suggestion that there were two functionally different pools of dynein in Jurkat cells, one a ring-like structure that pulled the MTOC to the contact site and the other one uniquely corresponding to the distribution of dynactin. This led to the hypothesis that the second pool of dynein drove vesicle transport. To address this possibility, we used siRNA to deplete the cell of dynactin. These studies showed that almost complete knockdown of dynactin (p150[superscript Glued]) had little effect on MTOC translocation but it also had little effect on a panel of Golgi vesicle markers, whose movement the literature suggested was dynein dependent. As an alternative, a Jurkat cell line expressing fluorescent CTLA4, a known marker for the secretory lysosomes was generated. CTLA4 accumulated at the contact site when Jurkat cells made contact with synthetic target cells. When we repeated the p150[superscript Glued] knockdown in these cells, we found that vesicle transport was blocked, whereas MTOC polarization remained normal. These studies suggest that dynein serves critical roles in both aspects of T cell effector function, the movement of the MTOC up to the cell-cell contact site and the movement of a special class of secretory vesicles up to the MTOC. By the combined processes of MTOC translocation and the minus end-directed movement of vesicles, T cells make it so that a concentrated pool of secretory vesicles are aimed to secrete locally only towards target cells. This ensures that the antigen-specificity of T cell activation is followed by a localized response aimed at the intended target cell. / text

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2007. / Härtill 3 uppsatser.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2009. / Title from PDF title page (viewed on Sept. 9, 2009). Includes bibliographical references.

Orientadores: Marilia de Moraes Castro, Luiza Sumiko Kinoshita / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-10T10:46:24Z (GMT). No. of bitstreams: 1 Marasca_RosinaMuto_M.pdf: 2857122 bytes, checksum: 9c907269750046ee751f61155a12e44e (MD5) Previous issue date: 2008 / Resumo: O estudo morfológico das estruturas secretoras encontradas em Rauvolfia sellowii Müll.Arg. foi realizado com o intuito de confirmar a presença de coléteres, através da análise da composição química, do secretado por eles produzido em órgãos vegetativos e reprodutivos, e efetuar um estudo comparado definindo tipo, número e posição ocupada. As estruturas secretoras florais também foram anatomicamente caracterizadas, com ênfase na cabeça dos estiletes. Uma grande quantidade de secreção esbranquiçada de aspecto gomoso é observada envolvendo ambas as faces dos primórdios foliares e a região adaxial das folhas jovens. Esta secreção é constituída principalmente por mucilagem (detectada pela reação PAS e pelo Vermelho de rutênio) e produzida por um número elevado de coléteres cônicos, os quais apresentam uma variação de comprimento e estão dispostos em duas ou três fileiras paralelas a superfície da base dos primórdios. Estas estruturas apresentam tanto origem axilar quanto marginal, são íntegras e persistem nas folhas adultas ocupando posição intrapeciolar. Coléteres responsáveis pela liberação de uma secreção incolor, constituída principalmente por mucilagem, são observadas nas brácteas folhosas e nas brácteas diminutas das inflorescências. Cada bráctea folhosa possui 9-13 coléteres polimorfos e destes, 2-4 são marginais do tipo standard e os demais são axilares cônicos semelhantes aos foliares. Nas brácteas diminutas é possível notar 2-4 coléteres marginais cônicos. A distensão da cutícula é observada nos coléteres foliares e das brácteas folhosas, e nos senescentes das brácteas diminutas. As estruturas secretoras encontradas nas flores são: epiderme da cabeça dos estiletes, nectários e laticíferos. Coléteres calicinais não foram observados. A epiderme da cabeça dos estiletes produz polissacarídeos e a presença de tricomas longos abaixo dos apêndices apicais diferencia a cabeça da flor funcionalmente masculina da feminina. A cabeça dos estiletes destas flores não apresenta adnação a qualquer dos verticilos florais e corresponde ao ¿tipo 2¿ descrito para Apocynaceae. O nectário é anelar na base e levemente bilobado no ápice; a vascularização é constituída por feixes concêntricos na região basal e por cordões floemáticos na região apical. O parênquima nectarífero é revestido por epiderme unisseriada, com estômatos ocupando preferencialmente a região apical. Os laticíferos são ramificados e estão presentes em todas as peças florais. A presença de um anel nectarífero e ausência de coléteres calicinais são caracteres relevantes em nível de tribo: considerados conjuntamente, eles corroboram a posição de R. sellowii em Vinceae / Abstract: The work here presented a morphological and anatomical study of the secretory structures of Rauvolfia sellowii Müll.Arg. The main goal of this study is to confirm the presence of colleters in the vegetative and reproductive organs of this species by analysing the chemical composition of the exsudate they produce and by doing a comparative study of their structural type, number and organization. An anatomical characterization of flower secretory strutures was also conducted, with emphasis on the style head. A substancial amount of a whitish, gluelike secretion was observed surrounding both faces of the young leaf primordia. This secretion is mainly composed by a mucilage (detected by the PAS and Ruthenium red reactions) produced by several, conical colleters organized in two to three rows parallel to the leaf primordia base. The observed colleters can be either axillary and marginal in origin, form an entire and undivided body, and are persistent even in mature leaves, where they have an intrapetiolar position. Other colleters secreting a colorless fluid, mainly composed by mucilage, were also observed on the leafy and minute bracts of the inflorescences. Each leafy bract bears 9-13 colleters, from which 2 to 4 are marginal and standard-type, and the remaining are axillary and resemble morphologically the conical colleters from the leaf primordia. The minute bracts, on the contrary, bear 2 to 4 marginal, conical colleters at the base. A distention of the cuticle was observed in the epidermal cells of the colleters at the leaf primordia and leafy bracts, and also on the senescent colleters at the minute bracts. Three types of secretory structures were found in the flowers of R. sellowii: epidermal cells of the style-head, nectaries and laticifers. No colleters were found at the base of the calyx lobes. The epidermal cells of the style-head produce mucilage, and the presence of long trichomes below the apical appendages of the style-head is a major distinctive characteristic of masculine functionally flowers. Regardless the flower type, the style-head is never fused to the androecium and thus correspond to the ¿type 2¿ organizational level described in Apocynaceae. The nectaries form an annular ring surrounding the ovary base and slightly bilobed at the apex. Vascularization of the organ is constituted by concentric bundles at the basal portion and phloematic bundles at the apical portion. The nectariferous parenchima is covered by a single epidermal layer, with stomata distributed preferentially at the apex. The observed laticifers are branched and are widely distributed in all floral organs. The presence of a conspicuous nectary ring surrounding the ovary and the absence of colleters at the base of the calyx lobes are diagnostic characteristics traditionally used in the tribal classification of Apocynaceae, and their co-ocurrence in R. sellowii corroborates its placement in the tribe Vinceae / Mestrado / Biologia Vegetal / Mestre em Biologia Vegetal

Orientador: Marilia de Moraes Castro, Kikyo Yamamoto / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-12T10:18:40Z (GMT). No. of bitstreams: 1 Dias_AnaCristinaAndradedeAguiar_D.pdf: 108033344 bytes, checksum: b2cd23adb70fa12713b032476a15fbe6 (MD5) Previous issue date: 2008 / Resumo: Este estudo tem como principal objetivo contribuir para o conhecimento morfológico de cinco espécies de Polygala L., das quais três ocorrem em restinga ( P. cyparissias A.St.-Hil. & Moq., P. laureola A.St.-Hil. & Moq. e P. paniculata L.) e duas em cerrado ( P. angulata L. e P. violacea Aubl. Emend Marques) no estado de São Paulo. Os principais pontos abordados na tese são a caracterização de estruturas secretoras e a elaboração de um inventário de caracteres morfológicos do eixo vegetativo. Destaca-se entre os resultados obtidos: a verificação de que as glândulas presentes no caule de P. laureola tratam-se de nectários extranupciais de origem estipular ocupando posição nodal. Além disso, foi possível constatar que as glândulas da inflorescência de P. laureola também são nectários extranupciais. Já em P. angulata, ductos secretores são observados no caule . Tais estruturas estão sendo identificadas como sítios de síntese de compostos hidrossolúveis - mucilagem. No inventário morfológico realizado nas cinco espécies de Polygala, foi evidenciado que a estrutura primária do caule se apresenta distintiva, enquanto que a estrutura secundária do caule e da raiz se apresenta conservativa. No estudo anatômico foliar, dois padrões estruturais são observados nas espécies estudadas de restinga e de cerrado; P. laureola, P. paniculata e P. violacea possuem características mesomórficas, P. cyparissias e P. angulata apresentam características xeromórficas. / Abstract: The purpose of this study is to contribute to the morphological knowledge of five species of Polygala L., three of which occur in the restinga ( P. cyparissias A.St.-Hil. & Moq., P. laureola A.St.-Hil. & Moq. and P. Paniculata L.) and the other two occur in the cerrado vegetation ( P. angulata L. and P. violacea Aubl. emend Marques) of São Paulo state, Brazil. The main points of this research are the characterization of the secretory structures and the survey of morphological features of the vegetative axis of these five species. Among the data obtained, it should be highlighted that the vegetative glands of P. laureola are stipular, extranuptial nectaries occupying a nodal position and that their inflorescence glands are also extranuptial nectaries. Secretory ducts observed in the stem of P. angulata are identified as sites of biosynthesis and secretion of mucilage. The morphological survey of the five Polygala species reveal that the primary stem structure is distinctive, whereas the secondary structure of the stem and the root is conservative. The leaf anatomy of these species shows two structural patterns occurring in the restinga and the cerrado vegetation: P. laureola, P paniculata and P. Violacea have mesomorphic characters and P. cyparissias and P. angulata have xeromorphic features. / Doutorado / Doutor em Biologia Vegetal

Orientadores: Sandra Maria Carmello Guerreiro, Silvia Rodrigues Machado / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-23T04:49:10Z (GMT). No. of bitstreams: 1 Tolke_ElisabethEmiliaAugustaDantas_M.pdf: 15837739 bytes, checksum: 8d91bccef86d47cf61ace6595cbf206b (MD5) Previous issue date: 2013 / Resumo: Tapirira guianensis Aubl. (Anacardiaceae) conhecida popularmente como pau-pombo é uma espécie importante para uso madeireiro, medicinal e pode ser empregada na recuperação de áreas degradadas e de matas ciliares. Diversas substâncias são produzidas em estruturas secretoras específicas, sendo a presença de canais e cavidades secretoras característica universal da família. Na literatura é relatada a presença de disco nectarífero intraestaminal nas flores de muitas Anacardiaceae. No entanto, estudos anatômicos e histoquímicos recentes não comprovaram a secreção de néctar por esta estrutura. Além disso, nestes trabalhos foi verificada a persistência do disco intraestaminal no fruto maduro de T. guianensis, bem como a presença de um endocarpo secretor em frutos não maduros. Aliado a estes fatores, a ontogenia de frutos e sementes também é um tema pouco explorado frente ao grande número de espécies da família. A anatomia dos frutos de Anacardiaceae tem-se mostrado de grande valor sistemático. Assim, o presente trabalho consistiu em verificar a estrutura e ultraestrutura do disco glandular de flores e frutos de T. guianensis, bem como examinar a natureza da secreção produzida e estudar a ontogenia do fruto e da semente. Com os resultados alcançados foi possível determinar que a glândula floral das flores hermafroditas de T. guianensis é uma glândula de secreção mista, produzindo néctar com predominância de sacarose, lipídios e substâncias fenólicas. Ultraestruturalmente esta glândula passa por mudanças profundas ao longo do desenvolvimento da flor, inicialmente rica em amiloplastos e posteriormente plastídios desprovidos de amido e mitocôndrias repletas de gotículas de óleo, indicando a mudança da secreção antes predominantemente hidrofílica para lipofílica. No que diz respeito à anatomia do fruto, observou-se que o mesmo possui características típicas da tribo Spondieae, porém algumas delas indicam uma condição menos derivada da espécie, como ausência de opérculo e endocarpo relativamente fino quando comparado com outras espécies da mesma tribo. O pericarpo possui grande quantidade de canais resiníferos na região do mesocarpo, epicarpo produzindo substâncias fenólicas e lipídios, e por meio de microscopia eletrônica de transmissão pôde-se observar o modo de secreção, as organelas envolvidas do processo, bem como a estrutura celular. A semente provém de um óvulo único, anátropo, bitegumentado, crassinucelado de funículo longo. A semente não possui camada mecânica, tem a exotesta e endotégmen ricos em substâncias fenólicas, cristais no mesotégmen, desenvolvimento de paquicalaza parcial, hipóstase fenólica e lipídica, permanência de funículo aderido ao envoltório da semente, formando um arilo vestigial. O embrião armazena grande quantidade de proteínas e amido, indicando uma condição de transição da espécie, pois em Anacardiaceae as reservas são constituídas principalmente por proteínas e lipídios. O fruto e semente apresentaram algumas características anatômicas possivelmente relacionadas à dispersão como, formação de aerênquima no mesocarpo interno e na mesotesta, acúmulo de amido no mesocarpo. O trabalho traz contribuições no estudo de glândulas florais em Anacardiaceae e na área de ontogenia de frutos e sementes / Abstract: Tapirira guianensis Aubl. (Anacardiaceae) well-known as "pau-pombo" is an important species with uses as timber, in medicine and can be employed recovering degraded areas and riparian forests. Several substances are produced in specific secretory structures and the presence of cavities and ducts are universal features in the family. In literature is reported the presence of an intrastaminal receptacular nectary in the flowers of many Anacardiaceae, however anatomical and histochemical recent studies did not support the nectar secretion by this structure. Furthermore, in other studies were found the persistence of intrastaminal receptacular gland in T. guianensis ripe fruits and the presence of a secretory endocarp in unripe fruits. Allied these factors, the ontogeny of fruits and seeds is also a relatively unexplored subject, in contrast with the large number of species from this family. The fruit anatomy of Anacardiaceae has proved great systematic value. Thus, the present study verified T. guianensis structure and ultrastructure of flowers and fruits intrastaminal gland and examined the nature of substances produced as well the fruit and seed development. With the results obtained it was possible provide that the T. guianensis floral gland of hermaphrodite flowers is a mixed secretion gland, producing nectar with sucrose predominance, lipids and fenolic substances. Ultrastructurally, this gland undergoes deep changes during the development of the flower, originally rich in amyloplasts and subsequently chloroplasts devoids of starch and mitochondria replete with oil droplets, indicating the change in the secretion predominantly hydrophilic to lipophilic. With respect to the fruit anatomy, it was observed characteristics typical of the tribe Spodieae, but some of them indicate a condition less derived of this species, such as lack of operculum and endocarp relatively thin compared to other species of the same tribe. Pericarp has a large number of resiniferous ducts in mesocarp region, and epicarp produces phenolic substances and lipids. By transmission electron microscopy it was possible to observe the way of secretion, the organelles involved in process and the cell structure. Seed comes from a single ovule, anatropous, bitegmic, crassinucelate with longe funicle. Seed does not have mechanical layer, has exotest and endotegmen rich in phenolic substances, crystals in mesotegmen, development of partial pachycalaza, phenolic and lipid hypostasis, permanence of the funicle attached to the seed-coat, forming a vestigial aril. The embryo stores large amounts of protein and starch, indicating a transitional condition in the species, because Anacardiaceae reserves comprehend mainly protein and lipids. Fruit and seed showed anatomical characteristics possibly related to dispersion, like formation of aerenchyma in the inner mesocarp and mesotest, starch accumulations in mesocarp. The work brings contributions in the study of Anacardiaceae floral glands and in the area of fruit and seeds ontogeny / Mestrado / Biologia Vegetal / Mestra em Biologia Vegetal

Non-Secretory Multiple Myeloma (NSMM) is characterized by typical morphological and pathological multiple myeloma (MM) characteristics and the absence of an M-protein on immunofixation electrophoresis with estimated prevalence of 3%. Among the NSMM cases there is a subset in which no cytoplasmic Immunoglobulin synthesis is detected, and this entity is called ‘’Non-Producing’’ Multiple Myeloma (NPMM). Plasma cell leukemia (PCL) is an aggressive form of MM characterized by high levels of abnormal plasma cells circulating in the peripheral blood. We present a rare case of non-producing variant of PCL. 75-year-old male was admitted due to anemia and thrombocytopenia. His CBC revealed hemoglobin of 9.0 g/dl and platelets were 9 k/ul. CMP showed creatinine of 1.34 mg/dl, total protein of 6 g/dl, albumin 3.6 g/dl and corrected calcium was normal. LDH was 204 IU/L. Peripheral smear review showed 8% circulating atypical plasmacytoid cells, normochromic normocytic anemia and thrombocytopenia. SPEP showed no monoclonal protein. IgA was normal. IgG, IgM were low 315 mg/dl and 20 mg/dl respectively. Serum beta-2 microglobulin was high (5.5, 1.1 – 2.4 mg/dl). Serum free kappa light chain was low (0.15, 0.33-1.94 mg/dl), lambda light chain and ratio was normal. Skeletal survey showed possible lytic lesions in right femur neck and subtrochanteric left femur. Bone marrow biopsy showed plasma cell myeloma involving 90-95% of bone marrow cellularity. The plasma cells show morphologic heterogeneity with prominent immature, plasmablastic and pleomorphic morphology. Flow cytometry shows a dominant abnormal CD45-dim population with expression of CD38, CD138, CD56 and CD117 (partial). The abnormal cells are negative for cytoplasmic kappa and lambda immunoglobulin light chains and negative for myeloid and lymphoid markers (by flow cytometry and immunohistochemical stains). Complex chromosomal analysis. Plasma cell FISH studies was positive for t(11;14). Based on suggested revised diagnostic criteria for PCL from outcomes of patients at mayo clinic, our patient was diagnosed with plasma cell leukemia. Given aggressive biology of this disease, he was started on VD-PACE chemotherapy. Bone marrow biopsy after cycle 1 chemotherapy showed no morphologic, immunophenotypic or flow cytometric features of a plasma cell neoplasm. Given excellent treatment response and discussion with transplant center subsequent cycle 2 was changed to Velcade, Revlimid and low-dose dexamethasone. He is scheduled for stem cell transplant later this month. Primary plasma cell leukemia (pPCL) is the most aggressive form of the plasma cell dyscrasias. The outcome of pPCL has improved with the introduction of autologous stem cell transplantation and combination approaches with novel agents, including bortezomib and immunomodulatory drugs, such as lenalidomide. This case highlights the challenges in diagnosis of non-producer primary plasma cell leukemia.

INTRODUCTION Multiple Myeloma is characterized by the neoplastic proliferation of plasma cells producing a monoclonal immunoglobulin which can be detected by analysis of the protein electrophoresis of serum (SPEP) and/or urine(UPEP) and/or serum free light chain analysis. Here ,we present a rare case of non-secretory multiple myeloma in which no measurable monoclonal heavy or light chains can be identified. CASE 68 year-old female presented to the hospital with symptoms of intractable back pain and rib pain along with 20 lb weight loss over the past 2 months. Labs were significant for mild anemia with a hemoglobin of 11mg/dl, WBC count 5.6 K/ul , platelet 199 K/ul, Chemistry panel showed mild hypernatremia with serum sodium 149, serum K 4.1, BUN 23mg/dl, serum creatinine 1.20 mg/dl, serum calcium levels elevated to 13.7 mg/dl and normal liver function tests. Imaging with Computed Tomography of chest, abdomen, pelvis showed extensive lytic lesions in axial and appendicular skeleton, with pathologic fractures involving T3 and T9 vertebrae. Skeletal bone survey showed innumerable lytic lesions involving the calvarium, C- spine, humerus, scapula, pelvis and bilateral femurs. A core needle biopsy of the right sacral iliac crest bone lesion was performed with pathology showing evidence of plasma cell neoplasm. SPEP showed hypogammaglobulinemia, normal serum kappa and lambda light chains and normal free light chain ratio. Serum immunofixation, UPEP and urine IFE did not show any evidence of monoclonal protein. Serum beta-2 microglobulin was elevated to 13.8 mg/L. Subsequent bone marrow biopsy revealed hyper cellular marrow with 95% cellularity, with 80% involvement by plasma cells, congo red stain negative, findings consistent with plasma cell myeloma. Cytogenetics were normal with FISH showing duplication of 1q, but negative for 17p deletion, t(4,14) and t(14,16). Hypercalcemia was managed with pamidronate. She was diagnosed with Revised International Staging System(R-ISS) Stage II non secretory multiple myeloma. Patient received palliative radiation therapy for lytic lesions. Treatment was initiated with standard of care regimen Velcade, Revlimid and Dexamethasone along with bisphosphonates. DISCUSSION Non secretory myeloma(NSMM) constitutes about 1-2% of all MM cases. It is classically defined as clonal bone marrow plasma cells ≥10% or biopsy proven plasmacytoma, evidence of end-organ damage with anemia, renal insufficiency likely secondary to hypercalcemia, bone lesions and lack of serum and urinary monoclonal protein on electrophoresis and immunofixation. Majority of these patients have M protein detectable in the cytoplasm of plasma cells by Immunohistochemistry, but have impaired secretion of the protein, or they can be non-producer MM. The overall survival (OS) and progression free survival( PFS) of NSMM is similar or superior to patients with secretory myeloma phenotype. Monitoring of the these patients for treatment response is challenging and is mainly on the basis of imaging studies like PET-CT or MRI and bone marrow evaluation.

No description available.