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排序方式: 共有8371条查询结果,搜索用时 718 毫秒
991.
992.
Katharine Trenholme Linda Marek Sandra Duffy Gabriele Pradel Gillian Fisher Finn K. Hansen Tina S. Skinner-Adams Alice Butterworth Che Julius Ngwa Jonas Moecking Christopher D. Goodman Geoffrey I. McFadden Subathdrage D. M. Sumanadasa David P. Fairlie Vicky M. Avery Thomas Kurz Katherine T. Andrews 《Antimicrobial agents and chemotherapy》2014,58(7):3666-3678
Therapies to prevent transmission of malaria parasites to the mosquito vector are a vital part of the global malaria elimination agenda. Primaquine is currently the only drug with such activity; however, its use is limited by side effects. The development of transmission-blocking strategies requires an understanding of sexual stage malaria parasite (gametocyte) biology and the identification of new drug leads. Lysine acetylation is an important posttranslational modification involved in regulating eukaryotic gene expression and other essential processes. Interfering with this process with histone deacetylase (HDAC) inhibitors is a validated strategy for cancer and other diseases, including asexual stage malaria parasites. Here we confirm the expression of at least one HDAC protein in Plasmodium falciparum gametocytes and show that histone and nonhistone protein acetylation occurs in this life cycle stage. The activity of the canonical HDAC inhibitors trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA; Vorinostat) and a panel of novel HDAC inhibitors on early/late-stage gametocytes and on gamete formation was examined. Several compounds displayed early/late-stage gametocytocidal activity, with TSA being the most potent (50% inhibitory concentration, 70 to 90 nM). In contrast, no inhibitory activity was observed in P. falciparum gametocyte exflagellation experiments. Gametocytocidal HDAC inhibitors caused hyperacetylation of gametocyte histones, consistent with a mode of action targeting HDAC activity. Our data identify HDAC inhibitors as being among a limited number of compounds that target both asexual and sexual stage malaria parasites, making them a potential new starting point for gametocytocidal drug leads and valuable tools for dissecting gametocyte biology. 相似文献
993.
Gabriele Tonni PhD MD Giampaolo Grisolia MD 《Journal of clinical ultrasound : JCU》2014,42(3):157-161
Abnormal intracranial translucency (IT) (fourth ventricle) and a Blake's pouch cyst with normal brain stem cavity may be valuable first‐trimester call signs of defects in the skull base. Here, we report a case of presumptive two‐dimensional sonographic diagnosis of occipital cephalocele that was posed at the time of 11–13 weeks aneuploidy scan. The two‐dimensional sonographic finding elicited a detailed fetal neuroscan that was performed using either multiplanar mode or a novel three‐dimensional reslicing and lightening technique. The use of three‐dimensional sonographic software and offline “navigation” within the volume of interest enabled operators to capture a diagnostic snapshot of the condition, enhancing quality imaging and early detection of the encephalic lesion. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound 42 :157–161, 2014 相似文献
994.
Gabriele Calaminus Wolfgang Dörffel Katja Baust Carmen Teske Marianne Riepenhausen Jürgen Brämswig Hans-Henning Flechtner Susanne Singer Andreas Hinz Günther Schellong 《Supportive care in cancer》2014,22(6):1519-1529
Purpose
The purpose of this study was to cross-sectionally assess quality of life (QoL) in survivors of childhood Hodgkin's disease (HD) in a cohort treated for HD in the successive German–Austrian therapy studies HD-78, HD-82, HD-85, HD-87, HD-90, HD-95, respectively, in accordance with the HD-Interval-Treatment recommendation between 1978 and 2002.Patients and methods
Data from QoL questionnaires were provided by 1,202 (66 %) of 1,819 invited survivors. These included the EORTC QLQ-C30 and socio-demographic variables. Data of a homogenous sub-sample (n?=?725) defined by age (21–41 years) and event- free-survival (no progress, relapse or secondary malignancies) were compared to an age-adjusted German reference sample (n?=?659).Results
While the global and physical QoL scores were comparable to those of the general population, survivors' mean scores were more than 10 points lower on the EORTC QLQ-C30 scales “Emotional” and “Social Functioning”. On the symptom scales, higher mean scores, exceeding 10 points, were obtained for the scales “Fatigue” and “Sleep”. In general, there was a gender effect showing lower functioning and higher symptom levels in women, most prominently in the group of young women (21–25 years). The results within the group of HD survivors could not be associated with the time since treatment, the age of HD survivors at diagnosis or the extent of therapy burden.Conclusion
Clinicians engaged in follow-up care should be sensitive to aspects of fatigue and related (emotional) symptoms in HD childhood cancer survivors and encourage their patients to seek further support if needed. 相似文献995.
996.
Gabriele Crimi Silvia Pica Claudia Raineri Ezio Bramucci Gaetano M. De Ferrari Catherine Klersy Marco Ferlini Barbara Marinoni Alessandra Repetto Maurizio Romeo Vittorio Rosti Margherita Massa Arturo Raisaro Sergio Leonardi Paolo Rubartelli Luigi Oltrona Visconti Maurizio Ferrario 《JACC: Cardiovascular Interventions》2013,6(10):1055-1063
997.
998.
Change in Cardiac Geometry and Function in CKD Children During Strict BP Control: A Randomized Study
999.
Daniele Campa Cosmeri Rizzato Gabriele Capurso Nathalia Giese Niccola Funel William Greenhalf Pavel Soucek Maria Gazouli Raffaele Pezzilli Claudio Pasquali Renata Talar-Wojnarowska Maurizio Cantore Angelo Andriulli Aldo Scarpa Krzysztof Jamroziak Gianfranco Delle Fave Eithne Costello Kay-Tee Khaw Federico Canzian 《Digestive and liver disease》2013,45(2):95-99
Pancreatic cancer is the fourth leading cause of cancer deaths in the European Union and in the USA, but little is known about its genetic susceptibility. The PANcreatic Disease ReseArch (PANDoRA) consortium was established to unite the efforts of different research groups; its aim is to create a large bio-database to uncover new genetic factors for pancreatic cancer risk, response to treatment, and patient survival. So far 2220 cases of pancreatic adenocarcinoma, a smaller number of cases of endocrine pancreatic tumours (n = 86), chronic pancreatitis (n = 272) and 3847 healthy controls have been collected. As a collective effort of the consortium, SNPs associated with pancreatic adenocarcinoma risk from a genome-wide association study performed in Caucasians were replicated. The possibility that the same genetic polymorphisms may influence patient survival as well was also addressed. This collective effort is particularly important for pancreatic cancer because it is a relatively rare disease for which little is known about aetiopathogenesis and risk factors. The recruitment of additional collaborators and partner institutions is continuously on-going. 相似文献
1000.
Anne-Kathrin Hechinger Kristina Maas Christoph Dürr Franziska Leonhardt Gabriele Prinz Reinhard Marks Ulrike Gerlach Maike Hofmann Paul Fisch Jürgen Finke Hanspeter Pircher Robert Zeiser 《Haematologica》2013,98(1):31-40
Despite advances in immunosuppressive regimens, acute graft-versus-host disease remains a frequent complication of allogeneic hematopoietic cell transplantation. Pathogenic donor T cells are dependent on correct attachment of small GTPases to the cell membrane, mediated by farnesyl- or geranylgeranyl residues, which, therefore, constitute potential targets for graft-versus-host disease prophylaxis. A mouse model was used to study the impact of a farnesyl-transferase inhibitor and a geranylgeranyl-transferase inhibitor on acute graft-versus-host disease, anti-cytomegalovirus T-cell responses and graft-versus-leukemia activity. Treatment of mice undergoing allogeneic hematopoietic cell transplantation with farnesyl-transferase inhibitor and geranylgeranyl-transferase inhibitor reduced the histological severity of graft-versus-host disease and prolonged survival significantly. Mechanistically, farnesyl-transferase inhibitor and geranylgeranyl-transferase inhibitor treatment resulted in reduced alloantigen-driven expansion of CD4 T cells. In vivo treatment led to increased thymic cellularity and polyclonality of the T-cell receptor repertoire by reducing thymic graft-versus-host disease. These effects were absent when squalene production was blocked. The farnesyl-transferase inhibitor and geranylgeranyl-transferase inhibitor did not compromise CD8 function against leukemia cells or reconstitution of T cells that were subsequently responsible for anti-murine cytomegalovirus responses. In summary, we observed an immunomodulatory effect of inhibitors of farnesyl-transferase and geranylgeranyl-transferase on graft-versus-host disease, with enhanced functional immune reconstitution. In the light of the modest toxicity of farnesyl-transferase inhibitors such as tipifarnib in patients and the potent reduction of graft-versus-host disease in mice, farnesyl-transferase and geranylgeranyl-transferase inhibitors could help to reduce graft-versus-host disease significantly without having a negative impact on immune reconstitution. 相似文献