Advances in the Imaging of Pituitary Tumors

© 2020 Elsevier Inc. In most patients with pituitary adenomas magnetic resonance imaging (MRI) is essential to guide effective decision-making. T1- and T2-weighted sequences allow the majority of adenomas to be readily identified. Supplementary MR sequences (e.g. FLAIR; MR angiography) may also help inform surgery. However, in some patients MRI findings are ‘negative’ or equivocal (e.g. with failure to reliably identify a microadenoma or to distinguish postoperative change from residual/recurrent disease). Molecular imaging [e.g. 11C-methionine PET/CT coregistered with volumetric MRI (Met-PET/MRCR)] may allow accurate localisation of the site of de novo or persistent disease to guide definitive treatment (e.g. surgery or radiosurgery)

MEKK1-MKK4-JNK-AP1 Pathway Negatively Regulates Rgs4 Expression in Colonic Smooth Muscle Cells

Background: Regulator of G-protein Signaling 4 (RGS4) plays an important role in regulating smooth muscle contraction, cardiac development, neural plasticity and psychiatric disorder. However, the underlying regulatory mechanisms remain elusive. Our recent studies have shown that upregulation of Rgs4 by interleukin (IL)-1b is mediated by the activation of NFkB signaling and modulated by extracellular signal-regulated kinases, p38 mitogen-activated protein kinase, and phosphoinositide-3 kinase. Here we investigate the effect of the c-Jun N-terminal kinase (JNK) pathway on Rgs4 expression in rabbit colonic smooth muscle cells. Methodology/Principal Findings: Cultured cells at first passage were treated with or without IL-1b (10 ng/ml) in the presence or absence of the selective JNK inhibitor (SP600125) or JNK small hairpin RNA (shRNA). The expression levels of Rgs4 mRNA and protein were determined by real-time RT-PCR and Western blot respectively. SP600125 or JNK shRNA increased Rgs4 expression in the absence or presence of IL-1b stimulation. Overexpression of MEKK1, the key upstream kinase of JNK, inhibited Rgs4 expression, which was reversed by co-expression of JNK shRNA or dominant-negative mutants for MKK4 or JNK. Both constitutive and inducible upregulation of Rgs4 expression by SP600125 was significantly inhibited by pretreatment with the transcription inhibitor, actinomycin D. Dual reporter assay showed that pretreatment with SP600125 sensitized the promoter activity of Rgs4 in response to IL-1b. Mutation of the AP1-binding site within Rgs

Developing decision support tools for rangeland management by combining state and transition models and Bayesian belief networks

State and transition models provide a simple and versatile way of describing vegetation dynamics in rangelands. However, state and transition models are traditionally descriptive, which has limited their practical application to rangeland management decision support. This paper demonstrates an approach to rangeland management decision support that combines a state and transition model with a Bayesian belief network to provide a relatively simple and updatable rangeland dynamics model that can accommodate uncertainty and be used for scenario, diagnostic, and sensitivity analysis. A state and transition model, developed by the authors for subtropical grassland in south-east Queensland, Australia, is used as an example. From the state and transition model, an influence diagram was built to show the possible transitions among states and the factors influencing each transition. The influence diagram was populated with probabilities to produce a predictive model in the form of a Bayesian belief network. The behaviour of the model was tested using scenario and sensitivity analysis, revealing that selective grazing, grazing pressure, and soil nutrition were believed to influence most transitions, while fire frequency and the frequency of good wet seasons were also important in some transitions. Overall, the integration of a state and transition model with a Bayesian belief network provided a useful way to utilise the knowledge embedded in a state and transition model for predictive purposes. Using a Bayesian belief network in the modelling approach allowed uncertainty and variability to be explicitly accommodated in the modelling process, and expert knowledge to be utilised in model development. The methods used also supported learning from monitoring data, thereby supporting adaptive rangeland management

Modern imaging in Cushing's disease.

Funder: Wellcome Trust Institutional Strategic Support Fund, University of CambridgeManagement of Cushing's disease is informed by dedicated imaging of the sella and parasellar regions. Although magnetic resonance imaging (MRI) remains the investigation of choice, a significant proportion (30-50%) of corticotroph tumours are so small as to render MRI indeterminate or negative when using standard clinical sequences. In this context, alternative MR protocols [e.g. 3D gradient (recalled) echo, with acquisition of volumetric data] may allow detection of tumors that have not been previously visualized. The use of hybrid molecular imaging (e.g. 11C-methionine positron emission tomography coregistered with volumetric MRI) has also been proposed as an additional modality for localizing microadenomas

Novel imaging techniques in refractory pituitary adenomas.

Accurate localization of the site(s) of active disease is key to informing decision-making in the management of refractory pituitary adenomas when autonomous hormone secretion and/or continued tumor growth challenge conventional therapeutic approaches. In this context, the use of non-standard MR sequences, alternative post-acquisition image processing, or molecular (functional) imaging may provide valuable additional information to inform patient management

Novel imaging techniques in refractory pituitary adenomas

Funder: Erasmus+; doi: http://dx.doi.org/10.13039/501100010790Funder: Wellcome Trust Institutional Strategic Support Fund, University of CambridgeAccurate localization of the site(s) of active disease is key to informing decision-making in the management of refractory pituitary adenomas when autonomous hormone secretion and/or continued tumor growth challenge conventional therapeutic approaches. In this context, the use of non-standard MR sequences, alternative post-acquisition image processing, or molecular (functional) imaging may provide valuable additional information to inform patient management