We evaluated results of temozolomide (TMZ) therapy in six patients, aged 34–78 years, presenting aggressive pituitary tumors. In all the patients tested O6-methylguanine-DNA methyltransferase (MGMT) ...immunoexpression in surgical specimens was absent. Patients received temozolomide 140–320 mg/day for 5 days monthly for at least 3 months. In two patients minimum time for evaluation could not be reached because of death in a 76-year-old man with a malignant prolactinoma and of severe neutro-thrombopenia in a 47-year-old woman with nonfunctioning pituitary adenoma. In two patients (a 34-year-old acromegalic woman and a 39-year-old woman with Nelson’s syndrome) no response was observed after 4 and 6 months, respectively, and the treatment was stopped. Conversely, two 52- and 42-year-old women with Cushing’s disease had long-term total clinical and radiological remissions which persisted after stopping temozolomide. We conclude that TMZ therapy may be of variable efficacy depending on—until now—incompletely understood factors. Cooperative work on a greater number of cases of aggressive pituitary tumors should be crucial to establish the indications, doses, and duration of temozolomide administration.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is considered "pauci-immune" with absent or mild glomerular tuft staining for immunoglobulin (Ig) and/or complement. ...However, it is not unusual to see some immune deposits (ID) within glomeruli on immunofluorescence (IF). We determined to evaluate the prevalence and clinical significance of immune deposits in ANCA-associated GN.
We included all patients with ANCA associated vasculitis with renal biopsies between January 2002 and May 2014: granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis and renal limited vasculitis. Patients were divided into Group A: biopsy without ID (≤2+ intensity of immunostaining) and Group B: biopsy with ID (>2+ intensity of immunostaining). Serum creatinine, estimated glomerular filtration rate (eGFR) at time of the biopsy, amount of proteinuria and hematuria, requirement of dialysis and extra renal involvement were recorded.
Fifty-three patients (75.4% females) were included. Mean age at biopsy was 66.3 years. Typical pauci-immune GN was found in 39 patients (73.5%, group A). In 14 patients (26.4%, group B) examination revealed substantial deposition of Ig or complement in the mesangium and/or along the glomerular capillary wall. The only difference comparing both groups was significantly higher proteinuria in group B (mean 1.6/24 h (SD: 10.7) vs. 0.8/24 h (SD: 7.6), p=0.0036).
In ANCA GN at least a quarter of patients were not "pauci-immune" (26.4%). In this subgroup, immune deposits were only associated with a significantly higher proteinuria. Further basic and clinical research is needed to elucidate the significance of immune deposition in ANCA GN.
Paracoccidioidomycosis is endemic in subtropical rainforests of Latin America. Acute/subacute presentations involve an aggressive dissemination throughout the lymphatic system, while chronic forms ...(more frequent) arise as differential diagnosis for other conditions involving lung, oropharynx, skin, and eventually the brain. We present the case of a man referred for evaluation and treatment of a possible lung tumor with brain metastasis. The finding of multibudded yeasts and the microbiological isolation of a dimorphic fungus identified as Paracoccidioides sp. from a brain biopsy prompted a cardinal change in prognosis and treatment. This case alerts on the importance of considering systemic fungal diseases as differential diagnosis of compatible clinical presentations in patients who had lived in, or visited, endemic areas.
Formalin‐fixed, paraffin‐embedded (FFPE), biobanked tissue samples offer an invaluable resource for clinical and biomarker research. Here, we developed a pressure cycling technology (PCT)‐SWATH mass ...spectrometry workflow to analyze FFPE tissue proteomes and applied it to the stratification of prostate cancer (PCa) and diffuse large B‐cell lymphoma (DLBCL) samples. We show that the proteome patterns of FFPE PCa tissue samples and their analogous fresh‐frozen (FF) counterparts have a high degree of similarity and we confirmed multiple proteins consistently regulated in PCa tissues in an independent sample cohort. We further demonstrate temporal stability of proteome patterns from FFPE samples that were stored between 1 and 15 years in a biobank and show a high degree of the proteome pattern similarity between two types of histological regions in small FFPE samples, that is, punched tissue biopsies and thin tissue sections of micrometer thickness, despite the existence of a certain degree of biological variations. Applying the method to two independent DLBCL cohorts, we identified myeloperoxidase, a peroxidase enzyme, as a novel prognostic marker. In summary, this study presents a robust proteomic method to analyze bulk and biopsy FFPE tissues and reports the first systematic comparison of proteome maps generated from FFPE and FF samples. Our data demonstrate the practicality and superiority of FFPE over FF samples for proteome in biomarker discovery. Promising biomarker candidates for PCa and DLBCL have been discovered.
Here, we report a pressure cycling technology‐SWATH data‐independent acquisition mass spectrometry workflow to reproducibly analyze punched and sectioned formalin‐fixed, paraffin‐embedded (FFPE) tissue proteomes in high‐throughput fashion. A FFPE tissue biobank can be thereby converted into a digital biobank of comprehensive tissue proteome archives which could be mined perpetually for clinical and biomarker research.
The leaf economics spectrum
and the global spectrum of plant forms and functions
revealed fundamental axes of variation in plant traits, which represent different ecological strategies that are ...shaped by the evolutionary development of plant species
. Ecosystem functions depend on environmental conditions and the traits of species that comprise the ecological communities
. However, the axes of variation of ecosystem functions are largely unknown, which limits our understanding of how ecosystems respond as a whole to anthropogenic drivers, climate and environmental variability
. Here we derive a set of ecosystem functions
from a dataset of surface gas exchange measurements across major terrestrial biomes. We find that most of the variability within ecosystem functions (71.8%) is captured by three key axes. The first axis reflects maximum ecosystem productivity and is mostly explained by vegetation structure. The second axis reflects ecosystem water-use strategies and is jointly explained by variation in vegetation height and climate. The third axis, which represents ecosystem carbon-use efficiency, features a gradient related to aridity, and is explained primarily by variation in vegetation structure. We show that two state-of-the-art land surface models reproduce the first and most important axis of ecosystem functions. However, the models tend to simulate more strongly correlated functions than those observed, which limits their ability to accurately predict the full range of responses to environmental changes in carbon, water and energy cycling in terrestrial ecosystems
.
Total water storage change in the subsurface is a key component of the global, regional and local water balances. It is partly responsible for temporal variations of the earth’s gravity field in the ...micro-Gal (1
μGal
=
10
−8
m
s
−2) range. Measurements of temporal gravity variations can thus be used to determine the water storage change in the hydrological system. A numerical method for the calculation of temporal gravity changes from the output of hydrological models is developed. Gravity changes due to incremental prismatic mass storage in the hydrological model cells are determined to give an accurate 3D gravity effect. The method is implemented in MATLAB and can be used jointly with any hydrological simulation tool. The method is composed of three components: the prism formula, the MacMillan formula and the point-mass approximation. With increasing normalized distance between the storage prism and the measurement location the algorithm switches first from the prism equation to the MacMillan formula and finally to the simple point-mass approximation. The method was used to calculate the gravity signal produced by an aquifer pump test. Results are in excellent agreement with the direct numerical integration of the Theis well solution and the semi-analytical results presented in Damiata, B.N., and Lee, T.-C., 2006. Simulated gravitational response to hydraulic testing of unconfined aquifers. Journal of Hydrology 318, 348–359. However, the presented method can be used to forward calculate hydrology-induced temporal variations in gravity from any hydrological model, provided earth curvature effects can be neglected. The method allows for the routine assimilation of ground-based gravity data into hydrological models.
PDF
