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Posttranscriptional Induction of Two Cu/Zn Superoxide Dismutase Genes in Arabidopsis Is Mediated by Downregulation of miR398 and Important for Oxidative Stress Tolerance[W]

Sunkar, Ramanjulu; Kapoor, Avnish; Zhu, Jian-Kang
Fonte: American Society of Plant Biologists Publicador: American Society of Plant Biologists
Tipo: Artigo de Revista Científica
Publicado em /08/2006 EN
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MicroRNAs (miRNAs) are a class of regulatory RNAs of ∼21 nucleotides that posttranscriptionally regulate gene expression by directing mRNA cleavage or translational inhibition. Increasing evidence points to a potential role of miRNAs in diverse physiological processes. miR398 targets two closely related Cu/Zn superoxide dismutases (cytosolic CSD1 and chloroplastic CSD2) that can detoxify superoxide radicals. CSD1 and CSD2 transcripts are induced in response to oxidative stress, but the regulatory mechanism of the induction is unknown. Here, we show that miR398 expression is downregulated transcriptionally by oxidative stresses, and this downregulation is important for posttranscriptional CSD1 and CSD2 mRNA accumulation and oxidative stress tolerance. We also provide evidence for an important role of miR398 in specifying the spatial and temporal expression patterns of CSD1 and CSD2 mRNAs. Our results suggest that CSD1 and CSD2 expression is fine-tuned by miR398-directed mRNA cleavage. Additionally, we show that transgenic Arabidopsis thaliana plants overexpressing a miR398-resistant form of CSD2 accumulate more CSD2 mRNA than plants overexpressing a regular CSD2 and are consequently much more tolerant to high light, heavy metals, and other oxidative stresses. Thus...

Cardiac Conduction through Engineered Tissue

Choi, Yeong-Hoon; Stamm, Christof; Hammer, Peter E.; Kwaku, Kevin F.; Marler, Jennifer J.; Friehs, Ingeborg; Jones, Mara; Rader, Christine M.; Roy, Nathalie; Eddy, Mau-Thek; Triedman, John K.; Walsh, Edward P.; McGowan, Francis X.; del Nido, Pedro J.; Cow
Fonte: American Society for Investigative Pathology Publicador: American Society for Investigative Pathology
Tipo: Artigo de Revista Científica
Publicado em /07/2006 EN
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In children, interruption of cardiac atrioventricular (AV) electrical conduction can result from congenital defects, surgical interventions, and maternal autoimmune diseases during pregnancy. Complete AV conduction block is typically treated by implanting an electronic pacemaker device, although long-term pacing therapy in pediatric patients has significant complications. As a first step toward developing a substitute treatment, we implanted engineered tissue constructs in rat hearts to create an alternative AV conduction pathway. We found that skeletal muscle-derived cells in the constructs exhibited sustained electrical coupling through persistent expression and function of gap junction proteins. Using fluorescence in situ hybridization and polymerase chain reaction analyses, myogenic cells in the constructs were shown to survive in the AV groove of implanted hearts for the duration of the animal’s natural life. Perfusion of hearts with fluorescently labeled lectin demonstrated that implanted tissues became vascularized and immunostaining verified the presence of proteins important in electromechanical integration of myogenic cells with surrounding recipient rat cardiomyocytes. Finally, using optical mapping and electrophysiological analyses...

Antibody content of rabbit milk and serum following inhalation or ingestion of respiratory syncytial virus and bovine serum albumin

Peri, Barbara A.; Theodore, Christine M.; Losonsky, Genevieve A.; Fishaut, J. M.; Rothberg, R. M.; Ogra, P. L.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1982 EN
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The contribution of bronchus-associated or gut-associated lymphoid tissues to the development of specific immunologic reactivity in lactating mammary glands was studied by evaluating the effect of the nature of the antigen and the route of immunization on milk antibody content. Groups of pregnant rabbits were immunized with respiratory syncytial virus (RSV) and bovine serum albumin (BSA) administered i.v., per oral (p.o.) or transtracheal (i.t.) routes. The response to RSV was characterized by the regular appearance of IgA anti-RSV in the colostrum, milk, bronchial, and intestinal secretions following p.o. or i.t. immunization, but not after i.v. immunization. RSV-specific IgG appeared in the colostrum, milk, and serum regardless of the route of immunization. On the other hand, the response to BSA by all three routes of immunization was characterized by the appearance of anti-BSA in serum, colostrum and milk which was solely associated with IgG. The anti-BSA isotype did not change during the 30-day nursing period and was not affected by BSA ingestion before or during pregnancy or during nursing. If BSA was reintroduced after 20 days of nursing, a sharp rise in the Ab content of milk occurred in p.o. but not i.v. immunized dams. This increased anti-BSA was also of the IgG isotype. These observations suggest that the isotypes of specific Ab responses in the lactating mammary gland of the rabbit may be determined by the physical and chemical nature of the antigens contacted on respiratory or intestinal mucosal surfaces.

Radiological diagnosis of recurrent colonic carcinoma at the anastomosis

Bartram, Clive; Hale, John E.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/1970 EN
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The barium enemas of 23 cases of end-to-end anastomosis following resection of a colonic carcinoma demonstrated that the normal anastomosis should be smooth, symmetrical, and have a regular mucosal pattern. In contrast the three patients reported with proven recurrent carcinoma at the anastomosis showed irregular asymmetrical filling defects1.

Inhibition of leucocyte migration as an index of rejection in renal transplant recipients

Richmond, D. E.; Doak, P. B.; North, J. D. K.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/1973 EN
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In a blind study, the peripheral blood leucocytes of fifteen recipients of cadaver kidney homografts have been checked at regular intervals for migration inhibition in the presence of antigen derived from donor spleen. Six of seven episodes of definite acute rejection were preceded or accompanied by migration inhibition, and four of seven probable acute rejection crisis were similarly accompanied by inhibition. No false positive tests were observed. The technique may be a useful adjunct to present methods of diagnosing acute homograft rejection.

The cellular networks of normal ovine medial collateral and anterior cruciate ligaments are not accurately recapitulated in scar tissue

Lo, Ian KY; Ou, Yong; Rattner, John-Paul; Hart, David A; Marchuk, Linda L; Frank, Cyril B; Rattner, Jerome B
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /03/2002 EN
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The purpose of this study was to characterize the cellular organization of the ovine medial collateral ligament (MCL) and anterior cruciate ligament (ACL) and compare this organization with that found in ligaments undergoing healing. Indirect immunofluorescence microscopy, used in combination with antibodies to cytoskeletal proteins, was employed to visualize individual ligament cells. Normal ligaments contained fusiform cells arranged in rows, which were stacked at regular intervals across the body of the ligament forming a three-dimensional cellular lattice. Each cell exhibited prominent cytoplasmic processes that extended for long distances through the extracellular matrix to adjacent cells, and these processes contained gap junctions. Thus the cells in rows and between rows were interconnected. The cells of the MCL and ACL scars were also arranged in rows, but these rows were shorter, irregularly arranged and closely packed into bundles resulting in tissue with a higher cellular density. In addition, cells transiting the cell cycle were detected in the scar but not in normal ligament. While the rows of cells in the normal ligament extended along the long axis of the ligament, the bundles of rows of ligament scar cells had a random orientation with respect to one another and to the region outside the scar. Over time both the ACL and the MCL scars displayed discontinuities in their cellular rows. In contrast to the scars of the MCL...

Nutrition pathways to the symphysis pubis

Gonçalves da Rocha, Rodrigo Carvalho; Chopard, Renato Paulo
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /03/2004 EN
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The blood supply of the symphysis pubis is still the subject of some debate. Classic anatomy books state that this joint is avascular, whereas some published works have shown blood vessels in young specimens. As several articular discs such as the knee menisci are known to have blood vessels in their peripheries, we decided to investigate the possible nutrition pathways to the interpubic disc and ligaments. We used 60 Wistar rats, male and female, aged between 28 and 32 days, or between 90 and 100 days. Samples were processed using a variety of techniques: regular histology, immunohistochemestry, India ink injection and corrosion casting. The interpubic disc consisted of an inner bearing portion and an outer fibrous rim. The interpubic ligaments and the fibrous rim were well vascularized in all groups. Marrow contacts between the interpubic disc and the subchondral bone were also observed. Blood vessels formed an authentic arterial circle embracing the joint, from which blood vessels branched into capillary loops facing the avascular inner bearing portion of the disc. These results confirm the need for future studies on the human symphysis pubis, to provide more details on its structure, which would enable clinicians such as physiotherapists to improve prognosis and treatment design. Future studies may also explain the pathways down which the hormone relaxin reaches its targets within this joint.

Morphological study of the perireticular nucleus in human fetal brains

Tulay, Cumhur Murat; Elevli, Levent; Duman, Uğur; Sarimehmetoğlu, Ayşe; Çavdar, Safiye
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /07/2004 EN
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The perireticular nucleus consists of scattered neurons that are located in the internal capsule. The presence of perireticular neurons in the rat, ferret, cat and human has been described previously. Evidence suggests that the perireticular neurons in various species decrease in number with increasing gestation, but in humans this finding has not been supported by quantitative data. This study aimed to investigate (1) the morphology of the human fetal perireticular neurons, (2) the average number of perireticular neurons within the anterior and posterior crus of the internal capsule per unit area, and (3) the magnitude and the stage of neuronal loss in the human perireticular nucleus subsequent to maturation. Nissl-stained sections of the internal capsule of human fetal brains of 24, 26.5, 32, 35, 37 and 39 weeks of gestation showed a number of clearly distinguishable large perireticular and small microglia cells. A regular increase of both perireticular and microglial cells was observed up to 32 weeks of gestation, after which a dramatic reduction in the number of both perireticular and microglia cells was observed. The average number of perireticular and the microglia cells per unit area, located within the posterior crus, was more than in the anterior crus of the internal capsule. In the adult...

Recovery of immunological responsiveness in thymectomized mice

Dukor, P.; Dietrich, F. M.; Rosenthal, M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1966 EN
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After a limited period of immunological unresponsiveness, neonatally thymectomized colony-bred Swiss mice were found to recover their ability to form haemagglutinins and haemolysins as well as their antibody-plaque-forming capacity following injection of sheep erythrocytes. No such spontaneous reconstitution was observed in F1-hybrids of highly inbred CBA and CBA-T6T6 mice. Adult thymectomized and irradiated Swiss mice similarly regained their ability to form haemolysins and haemagglutinins, but no regeneration of antibody-plaque production occurred in these mice during the period of observation. No regular correlation was found between the degree of immunological deficiency on the one hand and the level of circulating lymphocytes or the histological appearance of the spleens on the other, following neonatal thymectomy or adult thymectomy and irradiation.

Platelet-Activating Factor Is Crucial in Psoralen and Ultraviolet A-Induced Immune Suppression, Inflammation, and Apoptosis

Wolf, Peter; Nghiem, Dat X.; Walterscheid, Jeffrey P.; Byrne, Scott; Matsumura, Yumi; Matsumura, Yasuhiro; Bucana, Cora; Ananthaswamy, Honnavara N.; Ullrich, Stephen E.
Fonte: American Society for Investigative Pathology Publicador: American Society for Investigative Pathology
Tipo: Artigo de Revista Científica
Publicado em /09/2006 EN
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Psoralen plus UVA (PUVA) is used as a very effective treatment modality for various diseases, including psoriasis and cutaneous T-cell lymphoma. PUVA-induced immune suppression and/or apoptosis are thought to be responsible for the therapeutic action. However, the molecular mechanisms by which PUVA acts are not well understood. We have previously identified platelet-activating factor (PAF), a potent phospholipid mediator, as a crucial substance triggering ultraviolet B radiation-induced immune suppression. In this study, we used PAF receptor knockout mice, a selective PAF receptor antagonist, a COX-2 inhibitor (presumably blocking downstream effects of PAF), and PAF-like molecules to test the role of PAF receptor binding in PUVA treatment. We found that activation of the PAF pathway is crucial for PUVA-induced immune suppression (as measured by suppression of delayed type hypersensitivity to Candida albicans) and that it plays a role in skin inflammation and apoptosis. Downstream of PAF, interleukin-10 was involved in PUVA-induced immune suppression but not inflammation. Better understanding of PUVA’s mechanisms may offer the opportunity to dissect the therapeutic from the detrimental (ie, carcinogenic) effects and/or to develop new drugs (eg...

Multiplexed Detection of Anthrax-Related Toxin Genes

Moser, Michael J.; Christensen, Deanna R.; Norwood, David; Prudent, James R.
Fonte: American Society for Investigative Pathology Publicador: American Society for Investigative Pathology
Tipo: Artigo de Revista Científica
Publicado em /02/2006 EN
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Simultaneous analysis of three targets in three colors on any real-time polymerase chain reaction (PCR) instrument would increase the flexibility of real-time PCR. For the detection of Bacillus strains that can cause inhalation anthrax-related illness, this ability would be valuable because two plasmids confer virulence, and internal positive controls are needed to monitor the testing in cases lacking target-specific signals. Using a real-time PCR platform called MultiCode-RTx, multiple assays were developed that specifically monitor the presence of Bacillus anthracis-specific virulence plasmid-associated genes. In particular for use on LightCycler-1, two triplex RTx systems demonstrated high sensitivity with limits of detection nearing single-copy levels for both plasmids. Specificity was established using a combination of Ct values and correct amplicon melting temperatures. All reactions were further verified by detection of an internal positive control. For these two triplex RTx assays, the analytical detection limit was one to nine plasmid copy equivalents, 100% analytical specificity with a 95% confidence interval (CI) of 9%, and 100% analytical sensitivity with a CI of 2%. Although further testing using clinical or environmental samples will be required to assess diagnostic sensitivity and specificity...

State Board of Medical Examiners: Regular Meeting

Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/1919 EN
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State Board of Medical Examiners: Regular Meeting

Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1920 EN
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AMD3465, a Novel CXCR4 Receptor Antagonist, Abrogates Schistosomal Antigen-Elicited (Type-2) Pulmonary Granuloma Formation

Hu, Jerry S.; Freeman, Christine M.; Stolberg, Valerie R.; Chiu, Bo Chin; Bridger, Gary J.; Fricker, Simon P.; Lukacs, Nicholas W.; Chensue, Stephen W.
Fonte: American Society for Investigative Pathology Publicador: American Society for Investigative Pathology
Tipo: Artigo de Revista Científica
Publicado em /08/2006 EN
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CXCR4 is a major receptor for CXCL12 and is known to participate in multiple physiological systems. The present study tested a second generation CXCR4 antagonist, AMD3465, for effects on highly defined models of Th1- and Th2-cell-mediated hypersensitivity-type pulmonary granuloma formation. Type-1 and type-2 granulomas were induced, respectively, by intravenous challenge of sensitized CBA/J mice with Mycobacteria bovis purified protein derivative- or Schistosoma mansoni egg antigen-coated beads. Before challenge, mice were implanted with osmotic pumps releasing AMD3465 at 5 μg/hour (6 mg/kg/day). Compared to vehicle, AMD3465 had minimal effect on type-1 inflammation or cytokine responses in draining lymph nodes, but the type-2 inflammation was significantly abrogated with reductions in lesion size and eosinophil content as well as abrogated interleukin (IL)-5, IL-10, and IL-13 cytokine production in draining lymph nodes. The biased effect of AMD3465 correlated with greater CXCR4 ligand expression in the type-2 model. Treatment during a primary response impaired lymph node IL-2 production after both Mycobacteria bovis purified protein derivative and Schistosoma mansoni egg antigen challenge indicating an unbiased effect during immune induction. In summary...

The Innate Pulmonary Granuloma : Characterization and Demonstration of Dendritic Cell Recruitment and Function

Chiu, Bo-Chin; Freeman, Christine M.; Stolberg, Valerie R.; Hu, Jerry S.; Komuniecki, Eric; Chensue, Stephen W.
Fonte: American Society for Investigative Pathology Publicador: American Society for Investigative Pathology
Tipo: Artigo de Revista Científica
Publicado em /03/2004 EN
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Granulomas are innate sequestration responses that can be modified by superimposed acquired immune mechanisms. The present study examined the innate stage of pulmonary granuloma responses to bead-immobilized Th1- and Th2-inducing pathogen antigens (Ags), Mycobacteria bovis purified protein derivative (PPD) and Schistosoma mansoni soluble egg Ags (SEA). Compared to a nonpathogen Ag, PPD and SEA bead elicited larger lesions with the former showing accelerated inflammation. Temporal analyses of cytokine and chemokine transcripts showed all Ag beads induced tumor necrosis factor-α mRNA but indicated biased interleukin (IL)-1, IL-6, and IL-12 expression with PPD challenge. All beads elicited comparable levels of CXCL9, CXL10, CCL2, CCL17, and CCL22 mRNA, but PPD beads caused biased CXCL2 CXCL5, CCL3, and CCL4 expression whereas both pathogen Ags induced CCL7. Immunohistochemical, electron microscopic, and flow cytometric analyses showed that Ag beads mobilized CD11c+ dendritic cells (DCs) of comparable maturation. Transfer of DCs from PPD Ag-challenged lungs conferred a Th1 anamnestic cytokine response in recipients. Surprisingly, transfer of DCs from the helminth SEA-challenged lungs did not confer the expected Th2 response, but instead rendered recipients incapable of Ag-elicited IL-4 production. These results provide in vivo evidence that lung DCs recruited under inflammatory conditions favor Th1 responses and alternative mechanisms are required for Th2 commitment.

Impaired Lung Dendritic Cell Activation in CCR2 Knockout Mice

Chiu, Bo-Chin; Freeman, Christine M.; Stolberg, Valerie R.; Hu, Jerry S.; Zeibecoglou, Kyriaki; Lu, Bao; Gerard, Craig; Charo, Israel F.; Lira, Sergio A.; Chensue, Stephen W.
Fonte: American Society for Investigative Pathology Publicador: American Society for Investigative Pathology
Tipo: Artigo de Revista Científica
Publicado em /10/2004 EN
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Dendritic cell (DC) recruitment is a hallmark event in antigen (Ag)-challenged lungs. We previously reported models for analyzing DC migration and activation in the lung after Th1- or Th2-eliciting pathogen Ag-bead challenge. To determine the role of chemokines in DC mobilization, we applied this analysis to CCR1, CCR2, CCR5, and CCR6 chemokine receptor knockout mice. Both Mycobacteria bovis protein Ags and helminthic, Schistosoma mansoni egg Ags elicited multiple chemokines, including CCR1, CCR2, CCR5, and to a lesser extent CCR6 ligands. DCs from wild-type lungs expressed transcripts for chemokine receptors, CCR1, CCR2, CCR5, and CXCR4. In all knockout strains, CD11c+ cells were recruited to Ag-beads likely because of receptor redundancy. However, DCs in CCR2−/− mice had significantly decreased MHCII and CD40 expression. This was associated with abrogated cytokine production in draining lymph node cultures. Analysis of local innate inflammation revealed a 50% reduction in macrophage recruitment in CCR2−/− mice. Bone marrow chimeras of mixed CCR2+/+ green fluorescent protein transgenic and CCR2−/− green fluorescent protein-negative cells confirmed the DC maturation defect was only among the latter population. In conclusion...

Increased Expression of β6-Integrin in Skin Leads to Spontaneous Development of Chronic Wounds

Häkkinen, Lari; Koivisto, Leeni; Gardner, Humphrey; Saarialho-Kere, Ulpu; Carroll, Joseph M.; Lakso, Merja; Rauvala, Heikki; Laato, Matti; Heino, Jyrki; Larjava, Hannu
Fonte: American Society for Investigative Pathology Publicador: American Society for Investigative Pathology
Tipo: Artigo de Revista Científica
Publicado em /01/2004 EN
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Integrin αvβ6 is an epithelial cell-specific receptor that is not normally expressed by resting epithelium but its expression is induced during wound healing. The function of αvβ6-integrin in wound repair is not clear. In the present study, we showed that β6-integrin expression was strongly up-regulated in the epidermis in human chronic wounds but not in different forms of skin fibrosis. To test whether increased β6-integrin expression plays a role in abnormal wound healing we developed four homozygous transgenic mouse lines that constitutively expressed human β6-integrin in the epithelium. The mice developed normally and did not show any histological abnormalities in the skin. The rate of experimental skin wound closure was unaltered and the wounds healed without significant scar formation. However, during breeding program 16.1 to 27.0% of transgenic mice developed spontaneous, progressing fibrotic chronic ulcers. None of the wild-type animals developed these lesions. The chronic lesions had areas with severe fibrosis and numerous activated macrophages and fibroblasts expressing transforming growth factor (TGF)-β. The level of TGF-β1 was significantly increased in the lesions as compared with normal skin. The findings suggest that increased αvβ6-integrin in keratinocytes plays an active part in abnormal wound healing possibly through a mechanism involving increased activation of TGF-β.

Progression in Cutaneous Malignant Melanoma Is Associated with Distinct Expression Profiles : A Tissue Microarray-Based Study

Alonso, Soledad R.; Ortiz, Pablo; Pollán, Marina; Pérez-Gómez, Beatriz; Sánchez, Lydia; Acuña, Ma Jesús; Pajares, Raquel; Martínez-Tello, Francisco J.; Hortelano, Carlos M.; Piris, Miguel A.; Rodríguez-Peralto, José L.
Fonte: American Society for Investigative Pathology Publicador: American Society for Investigative Pathology
Tipo: Artigo de Revista Científica
Publicado em /01/2004 EN
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Cutaneous malignant melanoma remains the leading cause of skin cancer death in industrialized countries. Clinical and histological variables that predict survival, such as Breslow’s index, tumor size, ulceration, or vascular invasion have been identified in malignant melanoma. Nevertheless, the potential relevance of biological variables still awaits an in-depth exploration. Using tissue microarrays (TMAs), we retrospectively analyzed 165 malignant melanoma samples from 88 patients corresponding to distinct histological progression phases, radial, vertical, and metastases. A panel of 39 different antibodies for cell cycle, apoptosis, melanoma antigens, transcription factors, DNA mismatch repair, and other proteins was used. Integrating the information, the study has identified expression profiles distinguishing specific melanoma progression stages. Most of the detected alterations were linked to the control of cell cycle G1/S transition; cyclin D1 was expressed in radial cases 48% (12 of 25) with significant lost of expression in vertical cases 14% (9 of 65), P = 0.002; whereas p16INK4a (89% in vertical versus 71% in metastatic cases, P = 0.009) and p27KIP1 (76% in radial versus 45% in vertical cases, P = 0.010) were diminished in advanced stages. The study also defines a combination of biological markers associated with shorter overall survival in patients with vertical growth phase melanoma...

KIT Mutations Are Common in Testicular Seminomas

Kemmer, Kathleen; Corless, Christopher L.; Fletcher, Jonathan A.; McGreevey, Laura; Haley, Andrea; Griffith, Diana; Cummings, Oscar W.; Wait, Cecily; Town, Ajia; Heinrich, Michael C.
Fonte: American Society for Investigative Pathology Publicador: American Society for Investigative Pathology
Tipo: Artigo de Revista Científica
Publicado em /01/2004 EN
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Expression of KIT tyrosine kinase is critical for normal germ cell development and is observed in the majority of seminomas. Activating mutations in KIT are common in gastrointestinal stromal tumors and mastocytosis. In this study we examined the frequency and spectrum of KIT mutations in 54 testicular seminomas, 1 ovarian dysgerminoma and 37 non-seminomatous germ cell tumors (NSGCT). Fourteen seminomas (25.9%) contained exon 17 point mutations including D816V (6 cases), D816H (3 cases), Y823D (2 cases), and single examples of Y823C, N822K, and T801I. No KIT mutations were found in the ovarian dysgerminoma or the NSGCTs. In transient transfection assays, mutant isoforms D816V, D816H, Y823D, and N822K were constitutively phosphorylated in the absence of the natural ligand for KIT, stem cell factor (SCF). In contrast, activation of T801I and wild-type KIT required SCF. Mutants N822K and Y823D were inhibited by imatinib mesylate (Gleevec, previously STI571) whereas D816V and D816H were both resistant to imatinib mesylate. Biochemical evidence of KIT activation, as assessed by KIT phosphorylation and KIT association with phosphatidylinositol (PI) 3-kinase in tumor cell lysates, was largely confined to seminomas with a genomic KIT mutation. These findings suggest that activating KIT mutations may contribute to tumorigenesis in a subset of seminomas...

Peripheral Tissue Involvement in Sporadic, Iatrogenic, and Variant Creutzfeldt-Jakob Disease : An Immunohistochemical, Quantitative, and Biochemical Study

Head, Mark W.; Ritchie, Diane; Smith, Nadine; McLoughlin, Victoria; Nailon, William; Samad, Sazia; Masson, Stephen; Bishop, Matthew; McCardle, Linda; Ironside, James W.
Fonte: American Society for Investigative Pathology Publicador: American Society for Investigative Pathology
Tipo: Artigo de Revista Científica
Publicado em /01/2004 EN
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Human prion diseases are rare fatal neurodegenerative conditions that occur as acquired, familial, or idiopathic disorders. A key event in their pathogenesis is the accumulation of an altered form of the prion protein, termed PrPSc, in the central nervous system. A novel acquired human prion disease, variant Creutzfeldt-Jakob disease, is thought to result from oral exposure to the bovine spongiform encephalopathy agent. This disease differs from other human prion diseases in its neurological, neuropathological, and biochemical phenotype. We have used immunohistochemistry and Western blot techniques to analyze the tissue distribution and biochemical properties of PrPSc in peripheral tissues in a unique series of nine cases of variant Creutzfeldt-Jakob disease. We have compared this with the distribution and biochemical forms found in all of the major subtypes of sporadic Creutzfeldt-Jakob disease and in a case of iatrogenic Creutzfeldt-Jakob disease associated with growth hormone therapy. The results show that involvement of the lymphoreticular system is a defining feature of variant Creutzfeldt-Jakob disease, but that the biochemical isoform of PrPSc found is influenced by the cell type in which it accumulates.