Structural Dissection of Epsin-1 N-Terminal Helical Peptide: The Role of Hydrophobic Residues in Modulating Membrane Curvature.

Spatiotemporal structural alterations in cellular membranes are the hallmark of many vital processes. In these cellular events, the induction of local changes in membrane curvature often plays a pivotal role. Many amphiphilic peptides are able to modulate membrane curvature, but there is little information on specific structural factors that direct the curvature change. Epsin-1 is a representative protein thought to initiate invagination of the plasma membrane upon clathrin-coated vesicles formation. Its N-terminal helical segment (EpN18) plays a key role in inducing positive membrane curvature. This study aimed to elucidate the essential structural features of EpN18 in order to better understand general curvature-inducing mechanisms, and to design effective tools for rationally controlling membrane curvature. Structural dissection of peptides derived from EpN18 revealed the decisive contribution of hydrophobic residues to (i) enhancing membrane interactions, (ii) helix structuring, (iii) inducing positive membrane curvature, and (iv) loosening lipid packing. The strongest effect was obtained by substitution with leucine residues, as this EpN18 analog showed a marked ability to promote the influx of octa-arginine cell-penetrating peptides into living cells.

Achievements of true whole-body imaging using a faster acquisition of the lower extremities in variable-speed continuous bed motion.

Variable-speed continuous bed motion 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT), a reliable imaging technique, allows setting the bed motion speed for arbitrary sections of the body. The purpose of this study was to evaluate the relationship between the PET image quality and the bed speed following shortening of the scanning time for the lower extremities to achieve whole-body acquisition optimization of the examination time. Four sets of images were created by editing four-phase dynamic whole-body PET/CT images acquired at a bed speed of 6 and 14 mm/s in the trunk and lower extremities, respectively. The signal-to-noise ratio (SNR) was calculated using regions of interest in the liver, gluteus muscles, thigh, and lower legs, and the relationship between the bed speed and the SNR was assessed. The number of patients with findings in the lower extremities among 967 cases was evaluated. Based on this relationship between the SNR and bed motion speed, it is reasonable to increase the speed of the lower extremities by up to three times that of the trunk. The findings from whole-body FDG-PET imaging revealed that the number of patients with detected lesions in the lower extremities was 6.6% (64/967), bone metastases were found in 2.6%, soft lesions in 1.8%, and inflammation in 2.3%. Images of the lower extremities, which have a better SNR than the trunk, can be acquired at a faster bed speed using the variable-speed continuous bed motion PET.

Comparison between dynamic whole-body FDG-PET and early-delayed imaging for the assessment of motion in focal uptake in colorectal area.

OBJECTIVES: Serial changes of focal uptake in whole-body dynamic positron emission tomography (PET) imaging were assessed and compared with those in early-delayed imaging to differentiate pathological uptake from physiological uptake in the colorectal area, based on the change in uptake shape. METHODS: In 60 patients with at least 1 pathologically diagnosed colorectal cancer or adenoma, a serial 3 min dynamic whole-body PET/computed tomography imaging was performed four times around 60 min after the administration of 18F-fluorodeoxyglucose (FDG) to create a conventional (early) image by summation. Delayed imaging was performed separately at 110 min after FDG administration. High focal uptake lesions in the colorectal area were visually assessed as "changed" or "unchanged" on serial dynamic imaging and early-delayed imaging, based on the alteration in uptake shape over time. These criteria on the images were used to differentiate pathological uptake from physiological uptake. RESULTS: In this study, 334 lesions with high focal FDG uptake were observed. Among 73 histologically proven pathological FDG uptakes, no change was observed in 69 on serial dynamic imaging and 72 on early-delayed imaging (sensitivity of 95 vs. 99%, respectively; ns). In contrast, out of 261 physiological FDG uptakes, a change in uptake shape was seen in 159 on dynamic PET imaging and 66 on early-delayed imaging (specificity of 61 vs. 25%, respectively; p < 0.01). High and similar negative predictive values for identifying pathological uptake were obtained by both methods (98 vs 99%, respectively). Thus, the overall accuracy for differentiating pathological from physiological FDG uptake based on change in uptake shape tended to be higher on serial dynamic imaging (68%) than on early-delayed imaging (41%; p < 0.01). CONCLUSIONS: Dynamic whole-body FDG imaging enables differentiation of pathological uptake from physiological uptake based on the serial changes in uptake shape in the colorectal area. It may provide greater diagnostic value than early-delayed PET imaging. Thus, this technique holds a promise for minimizing the need for delayed imaging.

Dynamic whole-body 18F-FDG PET for differentiating abnormal lesions from physiological uptake.

PURPOSE: Serial assessment of visual change in 18F-FDG uptake on whole-body 18F-FDG PET imaging was performed to differentiate pathological uptake from physiological uptake in the urinary and gastrointestinal tracts. METHODS: In 88 suspected cancer patients, serial 3-min dynamic whole-body PET imaging was performed four times, from 60 min after 18F-FDG administration. In dynamic image evaluation, high 18F-FDG uptake was evaluated by two nuclear medicine physicians and classified as "changed" or "unchanged" based on change in uptake shape over time. Detectability of pathological uptake based on these criteria was assessed and compared with conventional image evaluation. RESULTS: Dynamic whole-body PET imaging provided images of adequate quality for visual assessment. Dynamic image evaluation was "changed" in 118/154 regions of high physiological 18F-FDG uptake (77%): in 9/19 areas in the stomach (47%), in 32/39 in the small intestine (82%), in 17/33 in the colon (52%), and in 60/63 in the urinary tract (95%). In the 86 benign or malignant lesions, 84 lesions (98%) were "unchanged." A high 18F-FDG uptake area that shows no change over time using these criteria is highly likely to represent pathological uptake, with sensitivity of 97%, specificity of 76%, PPV of 70%, NPV of 98%, and accuracy of 84%. CONCLUSION: Dynamic whole-body 18F-FDG PET imaging enabled differentiation of pathological uptake from physiological uptake in the urinary and gastrointestinal tracts, based on visual change of uptake shape.

Increased 18F-FDG accumulation in the tonsils after chemotherapy for pediatric lymphoma: a common physiological phenomenon.

OBJECTIVE: Increased 18F-fluorodeoxyglucose (FDG) uptake in the tonsils after the completion of chemotherapy in patients with lymphoma may be misdiagnosed as tumor recurrence. This study aimed to investigate the changes in physiological FDG uptake in the tonsils during and after chemotherapy in pediatric patients with lymphoma. METHODS: A total of 47 FDG-PET/CT scans acquired from 13 pediatric patients with lymphoma (before chemotherapy [preC] = 9; during chemotherapy [durC] = 12; within 1 month after the end of chemotherapy [endC] = 11; and after achieving complete response [postC] = 15) were retrospectively included in this study. FDG uptake in the palatine tonsils was assessed using maximum standardized uptake value (SUVmax). The relative size of the palatine tonsils was calculated as the tonsil-pharyngeal ratio (TPR). Serial changes in the SUVmax and TPR were evaluated. RESULTS: The mean SUVmax was 3.7 ± 1.7, 2.6 ± 0.7, 2.3 ± 0.8, and 6.2 ± 1.6, at the preC, durC, endC, and postC scans, respectively (p < 0.0001); TPR was 59.0 ± 11.2%, 58.3 ± 9.4%, 54.4 ± 7.9%, and 62.2 ± 12.0% in these groups, respectively, with no significant inter-group differences. TPR and SUVmax showed no correlation. CONCLUSIONS: Increased physiological FDG uptake in the tonsils is commonly observed after the completion of chemotherapy, even in the absence of reactive hypertrophy.

Active Bone Marrow With Focal FDG Accumulation Mimicking Bone Metastasis With a Case of Early Esophageal Cancer.

A 68-year-old man underwent F-FDG PET/CT for the staging of esophageal carcinoma discovered by a medical checkup. Increased focal accumulation in some vertebrae, right humerus, and right femoral bone was noted on FDG-PET, whereas CT showed relatively high attenuation, and MRI showed hypointense lesions on T1- and T2-weighted imaging. A bone biopsy revealed mildly hypercellular bone marrow in the thoracic spine with FDG accumulation and markedly hypocellular bone marrow in the pelvic bone without an increased uptake. InCl scintigraphy showed a similar distribution and confirmed the diagnosis of bone marrow reconversion.

Validity of image-defined risk factors in localized neuroblastoma: A report from two centers in Western Japan.

BACKGROUND: Japanese Neuroblastoma Study Group (JNBSG) has been employing image-defined risk factors (IDRFs) since 2010. However, the report from INRG in 2011 supplemented description stating that isolated contact is considered to be IDRF-positive only in renal vessels. The aim of this study was to evaluate the validity of IDRFs by comparing the previous (PG) and new guidelines (NG). METHODS: IDRFs of patients with localized neuroblastoma treated at two centers in Western Japan from 2002 to 2013 were retrospectively reviewed by radiologists. RESULTS: 47 neuroblastomas (abdomen 38, pelvis 2, mediastinum 7) were evaluated. For abdominal neuroblastomas, IDRFs were present in 15/38 (39.5%) using PG and in 31/38 (81.6%) using NG. Moreover, the IDRF-positive rate increased from 26.7% (4/15) to 80.0% (12/15) in 15 cases diagnosed during mass screening. Of the IDRF-positive cases, complete primary resection was achieved in 2/15 (13.3%) using PG and 17/31 patients (54.8%) using NG. There were two major surgical renal complications in the IDRF-positive cases based on the use of either guidelines, and the specificity decreased from 64% to 19%. CONCLUSIONS: According to NG, the IDRF-positive rate increased, and the resection rate decreased. NG may overestimate surgical risks, leading to unnecessary chemotherapy and a prolonged hospital stay.

Increased ubiquitination and the crosstalk of G protein signaling in cardiac myocytes: involvement of Ric-8B in Gs suppression by Gq signal.

Hyperactivation of Gq signaling causes cardiac hypertrophy, and ß-adrenergic receptor-mediated Gs signaling is attenuated in hypertrophic cardiomyocytes. Here, we found the increase in a global ubiquitination in hypertrophic mouse heart. The activation of Gq signaling resulted in the ubiquitination of Gαs in neonatal rat cardiomyocytes, reduced Gαs expression, and suppressed cAMP response to ß-adrenergic receptor stimulation. Ectopic expression of Gαq induced a similar suppression, which is due to the degradation of Gαs by a ubiquitin-proteasome pathway. Co-expression of Ric-8B, a positive regulator of Gαs, effectively canceled the Gαq-induced ubiquitination of Gαs and recovered the cAMP accumulation. In vitro, Gαq competes for the binding of Gαs to Ric-8B. These data show a new role of Ric-8B in the crosstalk of two distinct G protein signaling pathways, which are possibly involved in a part of mechanisms of chronic heart failure.