Epithelial metaplasia occurs when one predominant cell type in a tissue is replaced by another, and is frequently associated with an increased risk of subsequent neoplasia. In both mouse and human pancreas, acinar-to-ductal metaplasia has been implicated in the generation of cancer precursors. We show that pancreatic epithelial explants undergo spontaneous acinar-to-ductal metaplasia in response to EGFR signaling, and that this change in epithelial character is associated with the appearance of nestin-positive transitional cells. Lineage tracing involving Cre/lox-mediated genetic cell labeling reveals that acinar-to-ductal metaplasia represents a true transdifferentiation event, mediated by initial dedifferentiation of mature exocrine cells to generate a population of nestin-positive precursors, similar to those observed during early pancreatic development. These results demonstrate that a latent precursor potential resides within mature exocrine cells, and that this potential is regulated by EGF receptor signaling. In addition, these observations provide a novel example of rigorously documented transdifferentiation within mature mammalian epithelium, and suggest that plasticity of mature cell types may play a role in the generation of neoplastic precursors.

TP53, encoding p53, is one of the most famous tumor suppressor genes. The majority of human cancers demonstrate the inactivation of the p53 pathway. Mutant p53 not only, no longer, functions as a tumor suppressor but can also exert tumor-promoting effects. The basic function of p53 is to respond to cellular stress. We herein review the recent advances in p53 research and focus on apoptosis, cell cycle arrest, and senescence in response to stress. We also review the clinical applications of p53-based therapy for human cancer.

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This synopsis outlines the Japanese guideline Version 2.0 for the data acquisition protocol of oncology FDG-PET/CT scans that was created by a joint task force of the Japanese Society of Nuclear Medicine Technology, the Japanese Society of Nuclear Medicine and the Japanese Council of PET Imaging, and was published in Kakuigaku-Gijutsu 2013; 33:377–420 in Japanese. The guideline aims at standardizing the PET image quality among PET centers and different PET camera models by providing criteria for the IEC body phantom image quality as well as for the patient PET image quality based on the noise equivalent count (NEC), NEC density and liver signal-to-noise ratio, so that the appropriate scanning parameters can be determined for each PET camera. This Version 2.0 covers issues that were not focused on in Version 1.0, including the accuracy of the standardized uptake value (SUV), effect of body size together with adjustment of scanning duration, and time-of-flight (TOF) reconstruction technique. Version 2.0 also presents data acquired with new PET camera models that were not tested in Version 1.0. Reference values for physical indicators of phantom image quality have been updated as well.

Alongside the two conventional unenhanced magnetic resonance (MR) angiographic techniques, namely time-of-flight and phase-contrast MR angiography, several novel techniques have since been developed, including electrocardiograph (ECG)-gated fast spin echo (FSE), steady-state free precession (SSFP), and arterial spin labeling. These techniques are increasingly being used to avoid severe complications caused by contrast materials, such as iodinated contrast material-induced nephropathy and gadolinium-induced nephrogenic systemic fibrosis. However, image acquisition and interpretation with these techniques are more complicated than with contrast-enhanced MR angiography because of numerous types of artifacts. Appropriate use of these techniques can allow diagnosis of vascular diseases in patients with chronic kidney disease without using contrast materials. For example, time-of-flight angiography is the main technique for evaluating intracranial arteries. Phase-contrast imaging is increasingly being used for physiologic evaluation rather than morphologic evaluation. Meanwhile, ECG-gated FSE MR angiography can show peripheral arteries in more detail. SSFP MR angiography with or without arterial spin labeling can provide high-resolution images of blood vessels including renal arteries, the aorta, and coronary arteries. Black-blood imaging is also used to evaluate vessel walls and intravascular abnormalities including plaque, dissection, and thrombi. The authors review the principles of the currently available unenhanced MR angiographic techniques, along with their advantages and limitations, and describe their clinical applications. This article should help readers select the most appropriate unenhanced MR angiographic technique to assess vascular diseases in patients with chronic kidney disease. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.312105075/-/DC1.

In 1963, a strain of SHR rats which developed spontaneously hypertension was isolated from Wistar rats by Okamoto and Aoki (JPN CIRC J 27: 282, 1963).In preliminary studies to investigate T-lymphocyte markers in rats we noted that SHR rats had reduced numbers of rosette forming cells in their thymuses when compared to other rat strains (CELL IMMUNOL 27: 52, 1976). Additional studies were undertaken to more clearly determine if additional impairment of immunological functions existed in this rat strain with hypertension.The percentage of rosette forming cells in the thymus and in the spleen of the eight strains was tested.In seven rat strains, about 60% thymus cells formed rosettes with guinea pig erythrocytes, whereas with the SHR rat strain only 18% of thymus cells formed rosettes.W/Mk rats, the original colony of the SHR rats, had 63% rosette formation.None of the strains showed any rosette forming cells in their spleens.The number of rosette forming cells progressively decreased with age. The blastogenesis of SHR rat lymphocytes to PHA and Con A was less than one fifth to that of the other rat strains including W/Mk rats, the original colony of SHR rats.Lymphocytes from 8-month-old SHR rats had significantly lower blastogenic responses than did lymphocytes of 2-monthold SHR rats. aFour month old rats were used . Table shows the results of antibody responses to SRBC of the SHR and other rat strains using the direct plaque-forming assay. Antibody responses of the 4 month old SHR rats was about one tenth to that of the other 6 rat strains. Delayed type hypersensitivity responses of SHR rats to SRBC were measured using the radioisotopic footpad assay. The footpad reaction of immunized SHR rats was significantly lower than that of immunized WKA rats. Ability of SHR rats to reject alloskin grafts was also investigated.The number of mean survival days of allogeneic skin from F344 rats was significantly prolonged when compared to WKA rats (data not presented). (Summary)The thymuses of young SHR rats before developing hypertension had reduced numbers of immature T-lymphocytes which were detected by the rosette formation test with guinea pig erythrocytes, whereas the thymuses of other eight rat strains tested contained about 60% rosetting cells. The number of rosetting cells progressively decreased with age. The blastogenic responses to PHA of the SHR rat lymphocytes was depressed to less than one fifth when compared to those of other rat strains including W/Mk rats, the original colony of the SHR rats.Other cell-mediated immune responses, including delayed hypersensitivity, allograft rejections, and a cooperation of T-and B-lymphocytes to produce humoral antibody formation were significantly depressed when compared to those of other rat strains. 590

Immunocompetent cell functions were evaluated in spontaneously hypertensive rats (SHR). Hematological studies revealed decreased absolute numbers of lymphocytes and increases number of polynucleic cells in the peripheral blood of SHR. The SHR had a reduced number of immature T lymphocytes in their thymuses in comparison with an original strain of Wistar rats, as detected by the rosette formation test with guinea pig erythrocytes. The antibody response to sheep red blood cells (SRBC) of the 3-month-old SHR was profoundly depressed and was about one-teeth that of the Wistar rats. Cell cooperation experiments suggest that the T lymphocytes of the SHR were selectively impaired in antibody responses to SRBC in cooperation with B lymphocytes. B lymphocytes from the bone marrow of the SHR were not affected and produced normal numbers of plaque-forming units. Cyclophosphamide treatment, which selectively depletes suppressor T lymphocytes, did not enhance the delayed-type hypersensitivity response to SRBC in SHR. This may rule out the possibility of the involvement of the suppressor mechanism in the T cell depression of the SHR.

This synopsis outlines the Japanese guideline Version 2.0 for the data acquisition protocol of oncology FDG-PET/CT scans that was created by a joint task force of the Japanese Society of Nuclear Medicine Technology, the Japanese Society of Nuclear Medicine and the Japanese Council of PET Imaging, and was published in KakuigakuGijutsu 2013; 33:377-420 in Japanese. The guideline aims at standardizing the PET image quality among PET centers and different PET camera models by providing criteria for the IEC body phantom image quality as well as for the patient PET image quality based on the noise equivalent count (NEC), NEC density and liver signal-to-noise ratio, so that the appropriate scanning parameters can be determined for each PET camera. This Version 2.0 covers issues that were not focused on in Version 1.0, including the accuracy of the standardized uptake value (SUV), effect of body size together with adjustment of scanning duration, and time-of-flight (TOF) reconstruction technique. Version 2.0 also presents data acquired with new PET camera models that were not tested in Version 1.0. Reference values for physical indicators of phantom image quality have been updated as well.The objective of this guideline is to define the criteria for the data acquisition protocol for oncology FDG-PET (PET/ CT) scans in order to standardize the PET image quality among PET centers and different PET camera models. It describes the method for phantom experiments and human image quality evaluation and provides recommended values as a reference. The optimum imaging protocol for each camera model can be determined by using this guideline as a manual, and by comparing the results with the recommended values.The Version 1.0 (Kakuigaku-Gijutsu 2009; 29:195-235) and the English synopsis [1] did not deal with the accuracy of SUV values, and did not provide references for scanning patients with large body weight, which inevitably degrades image quality and requires longer scanning duration. Furthermore, new reconstruction techniques such as time-offlight (TOF) and point-spread-function (PSF) have become available, which affect image spatial resolution and noise in a way different from the conventional OSEM reconstruction technique. To address these issues, the joint task force again worked on the data of phantom and patient scans acquired with PET cameras currently used in Japan, including new PET camera models installed after Version