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Pituitary adenomas are common benign intracranial neoplasms. However, their tumorigenesis is not yet clearly defined. Inactivation of genes involved in the negative cell-cycle regulatory p15(INK4b) - p16(INK4a) -cyclin D/CDK4-RB1-mediated pathway (RB1 pathway) is one of the most common and important mechanisms in the growth advantage of tumor cells. Recently, much attention has been focused on the importance of alternative mechanisms of gene inactivation, particularly promoter hypermethylation in the transcriptional silencing of such tumor-suppressor genes. Based on the rare occurrence of inactivation by gene mutations and deletions of the RB1 pathway in pituitary adenomas, we investigated the deregulation of the RB1 pathway in 42 sporadic human pituitary adenomas, especially focusing on the methylation status of this pathway as determined by a methylation-specific polymerase chain reaction assay. Homozygous deletion of the p15(INK4b) or p16(INK4a) gene was detected in one adenoma each. Amplification of the CDK4 gene was not apparent in any of the pituitary adenomas presently examined. Promoter hypermethylation of the p15(INK4b), p16(INK4a), and RB1 genes was detected in 15 (35.7%), 30 (71.4%), and 12 (28.6%) of the adenomas, respectively. Promoter hypermethylation of the p15(INK4b) gene coincided with p16(INK4a) alteration and/or RB1 methylation, whereas p16(INK4a) and RB1 methylations tended to be mutually exclusive (p = 0.019). Thus, the vast majority of the adenomas (38 of 42, 90.5%) displayed alterations of the RB1 pathway. None of the clinicopathologic features, including the proliferation cell index, was significantly correlated with any particular methylation status. Our results suggest that inactivation of the RB1 pathway may play a causal role in pituitary tumorigenesis, with hypermethylation of the p16(INK4a) gene being the most common deregulation, and further provide evidence that RB1 and p16(INK4a) methylations tend to be mutually exclusive but occasionally coincide with p15(INK4b) methylation.

Iron enrichment to high‐nutrient low‐chlorophyll (HNLC) regions is being considered as a possible way of atmospheric CO2 sequestration to the deep sea. Mesoscale iron‐enrichment to the HNLC subarctic Pacific induced a massive diatom bloom and led to a large decrease in pCO2. In response to the diatom bloom, the heterotrophic dinoflagellate Gyrodinium sp. increased and phagotrophically fed on the diatoms up to 12 times their length. Mathematical simulations show the carbon fixed by diatoms is mostly respired by Gyrodinium sp. in the sea surface. The emergence of initially rare species and their key biogeochemical roles were unexpected due to our limited understanding of food‐web components. This indicates that the prediction of ecosystem responses to natural or anthropogenic perturbation remains a challenging issue. Effective carbon sequestration as a geoengineering technique may not be accomplished by purposeful iron‐enrichment, at least in the western subarctic Pacific where rapid‐growth diatom grazers stand by.

Purpose To examine the diagnostic performance of high-spatial-resolution (HSR) CT with 0.25-mm section thickness for evaluating renal artery in-stent restenosis. Materials and Methods A 0.05-mm wire phantom and vessel phantoms with renal stents with in-stent stenotic sections of varying diameters were scanned with both an HSR CT scanner equipped with 160-section multi-detector rows (0.25-mm section thickness) and a conventional CT scanner. The wire phantom was used to analyze modulation transfer function (MTF). With the vessel phantoms, the error rates were calculated as the absolute difference between the measured diameters and true diameters divided by the true diameters at the narrowing sections. For qualitative evaluation, overall image quality and diagnostic accuracy for evaluating stenosis in three stages were assessed by two radiologists. Statistical analyses included the paired t test, Wilcoxon signed-rank test, and McNemar test. Results HSR CT achieved 24.3 line pairs per centimeter ± 0.5 (standard deviation) and 29.1 line pairs per centimeter ± 0.4 at 10% and 2% MTF, respectively; and conventional CT was 12.5 line pairs per centimeter ± 0.1 and 14.3 line pairs per centimeter ± 0.1 at 10% and 2% MTF, respectively. The mean error rate of the measured diameter at HSR CT (8.0% ± 5.8) was significantly lower than that at at conventional CT (16.9% ± 9.3; P < .001). Image quality at HSR CT was significantly better than that at conventional CT (P < .001), but HSR CT was not significantly superior to conventional CT in terms of diagnostic accuracy. Conclusion Compared with conventional CT, high-spatial-resolution CT achieved spatial resolutions of up to 29 line pairs per centimeter at 2% modulation transfer function and yielded improved measurement accuracy for the evaluation of in-stent restenosis in a phantom study of renal artery stents. Published under a CC BY 4.0 license.