100,356 research outputs found
18-Fluorocholine PET/CT to detect local recurrence of prostatic cancer: correlation with serum PSA levels and Cancer Gleason Score (CGS).
No full textThe Trypanosoma brucei cAMP phosphodiesterases TbrPDEB1 and TbrPDEB2: flagellar enzymes that are essential for parasite virulence
No full textCyclic nucleotide specific phosphodiesterases (PDEs) are pivotal regulators of cellular signaling. They are also important drug targets. Besides catalytic activity and substrate specificity, their subcellular localization and interaction with other cell components are also functionally important. In contrast to the mammalian PDEs, the significance of PDEs in protozoal pathogens remains mostly unknown. The genome of Trypanosoma brucei, the causative agent of human sleeping sickness, codes for five different PDEs. Two of these, TbrPDEB1 and TbrPDEB2, are closely similar, cAMP-specific PDEs containing two GAF-domains in their N-terminal regions. Despite their similarity, these two PDEs exhibit different subcellular localizations. TbrPDEB1 is located in the flagellum, whereas TbrPDEB2 is distributed between flagellum and cytoplasm. RNAi against the two mRNAs revealed that the two enzymes can complement each other but that a simultaneous ablation of both leads to cell death in bloodstream form trypanosomes. RNAi against TbrPDEB1 and TbrPDEB2 also functions in vivo where it completely prevents infection and eliminates ongoing infections. Our data demonstrate that TbrPDEB1 and TbrPDEB2 are essential for virulence, making them valuable potential targets for new PDE-inhibitor based trypanocidal drugs. Furthermore, they are compatible with the notion that the flagellum of T. brucei is an important site of cAMP signaling.--Oberholzer, M., Marti, G., Baresic, M., Kunz, S., Hemphill, A., Seebeck, T. The Trypanosoma brucei cAMP phosphodiesterases TbrPDEB1 and TbrPDEB2: flagellar enzymes that are essential for parasite virulence
Letter, [Author unclear] to Paulina T. Merritt
No full textHandwritten letter to Paulina Merritt from an unknown author, October 1, 1876.
[F-18]fluorocholine PET/CT imaging for the detection of recurrent prostate cancer at PSA relapse: experience in 100 consecutive patients
No full textPurpose: We evaluated the potential of PET/CT and [F-18] fluoromethylcholine (FCH) in the assessment of suspected recurrence of prostate cancer after treatment. Methods: One hundred consecutive prostate cancer patients with a persistent increase in serum PSA (> 0.1 ng/ml) after radical prostatectomy ( 58 cases), radiotherapy ( 21 cases) or hormonal therapy alone ( 21 cases) were investigated. After injection of 3.7 - 4.07 MBq/kg of FCH, both early ( at 60 min) PET/CT scans were performed in 43 patients, delayed PET/CT scans in 53 patients and early PET/CT scans in four patients. Results: Of the 100 patients, 54 ( PSA 0.22 - 511.79 ng/ml) showed positive FCH PET/CT scans. Thirty-seven patients had bone and/or abdominal lymph node uptake, while 17 showed pelvic activity. Malignant disease was confirmed in all but one. Delayed SUVmax of bone metastases was significantly higher (p< 0.0001 by paired t test) than that measured at < 15 min, whereas no differences were observed between early and delayed SUVs of malignant lymph nodes or pelvic disease. Forty-six patients ( PSA 0.12 - 14.3 ng/ml) showed negative FCH PET/CT scans. Of the negative PET/CT scans, 89% were obtained in patients with serum PSA < 4 ng/ml and 87% in patients with a Gleason score < 8. In none of these cases could recurrent tumour be proven clinically during a follow-up of 6 months. Conclusion: FCH PET/CT is not likely to have a significant impact on the care of prostate cancer patients with biochemical recurrence until PSA increases to above 4 ng/ml. However, in selected patients, FCH PET/CT helps to exclude distant metastases when salvage local treatment is intended
18F-Choline PET/CT in early re-staging of prostate cancer patients at high-risk for recurrence
No full textMalignant struma ovarii harboring a unique NRAS mutation: case report and review of the literature
No full textStruma ovarii (SO), a rare tumor containing at least 50% of thyroid tissue, represents approximately 5% of all ovarian teratomas; its malignant transformation rate is reported to occur in up to 10% of cases and metastases occur in about 5-6% of them. We describe a 36-year old woman who underwent laparoscopic left annessectomy two years earlier because of an ovarian cyst. Follow-up imaging revealed a right adnexal mass, ascitis and peritoneal nodes that were diagnosed as comprising a malignant SO with peritoneal secondary localizations at histopathology performed after intervention. Restaging with F-18-FDG-PE T/CT scan, abdominal CT and ultrasonography showed abnormalities in the perihepatic region and presacral space and left hypochondrium localizations. The patient underwent thyroidectomy, hepatic nodulectomy and cytoreductive peritonectomy: histopathological examination did not show any malignant disease in the thyroid and confirmed the presence of peritoneal localizations due to malignant SO; molecular analysis detected NRAS Q61K mutation in exon 3, whereas no mutations were identified on the BRAF gene. The patient underwent radioiodine treatment: serum Tg was decreased at first follow-up after three months of I-131-therapy. We believe that our case raises some interesting considerations. First, pathologists should be aware of this entity and should check for the presence of point mutations suggesting an aggressive disease behavior, which could be beneficial for an optimal therapeutic approach. Second, although most of the knowledge in this field comes from case reports, efforts should be made to standardize the management of patients affected by malignant SO, including use of practice guidelines
Complete metabolic remission with Gefitinib in a hemodialysis patient with bone metastases from non-small cell lung cancer.
No full textGefitinib is highly active in patients with advanced or metastatic non-small cell lung cancer (NSCLC) harboring activating mutation of the epidermal growth factor receptor (EGFR) gene. The feasibility and the degree of response to treatment with gefitinib in patients with chronic renal failure (CRF) undergoing hemodialysis has not yet been fully described in literature. We describe the case of a 70-year-old man with CRF undergoing hemodialysis three times-a-week who developed vertebral and rib bone metastasis three years after lobectomy. The bone biopsy confirmed the pulmonary origin and pyrosequencing analysis revealed deletion in E746-E750 of exon 19. We started daily administration of 250 mg gefitinib with no changes in the hemodialysis schedule. Gefitinib was well-tolerated without any adverse event. After three months, the F-18-fluoro-2deoxy-d-glucose positron emission tomography/computed tomography (FDG PET/CT) showed complete metabolic remission of bone lesions. The patient is still under treatment and maintains response (30 months to date). To our knowledge, this is the first description of complete metabolic remission in this type of patient. In conclusion, gefitinib has been safely administered to a patient with NSCLC with EGFR-activating mutation undergoing chronic hemodialysis and its use has achieved an excellent and prolonged response on bone metastases
Handwritten biographical information on Paulina T. McClung Merritt
No full textA handwritten biography of Paulina T. McClung Merritt by an unknown author, 1892.
Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection.
No full textIFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells
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