Search

Vertebrates exhibit patterned epidermis, exemplified by scales/interscales in mice tails and grooves/ridges on the human skin surface (microtopography). Although the role of spatiotemporal regulation of stem cells (SCs) has been implicated in this process, the mechanism underlying the development of such epidermal patterns is poorly understood. Here, we show that collagen XVII (COL17), a niche for epidermal SCs, helps stabilize epidermal patterns. Gene knockout and rescue experiments revealed that COL17 maintains the width of the murine tail scale epidermis independently of epidermal cell polarity. Skin regeneration after wounding was associated with slender scale epidermis, which was alleviated by overexpression of human COL17. COL17-negative skin in human junctional epidermolysis bullosa showed a distinct epidermal pattern from COL17-positive skin that resulted from revertant mosaicism. These results demonstrate that COL17 contributes to defining mouse tail scale shapes and human skin microtopography. Our study sheds light on the role of the SC niche in tissue pattern formation. Mammals exhibit epidermal patterning, as seen in mouse tail scales and human skin microtopography. In this article, the authors demonstrate that type XVII collagen (COL17), a niche for epidermal stem cells, modulate epidermal patterning in mice and humans. COL17 further prevents wound-induced epidermal deformation. This study paves the way for elucidating the role of the stem cell niche in tissue pattern formation.

Photodynamic therapy (PDT) utilizes photochemical reactions induced by a photosensitizer and light in the target tissue and is used to treat various cancers. There is a high degree of anticipation of success regarding the application of PDT with talaporfin (photosensitizer) for gastric cancer. Olaparib is an oral inhibitor of Poly (ADP-Ribose) polymerase (PARP) and has demonstrated optimal efficacy and clinical activity in trials. Therefore, the aim of the present study was to investigate the efficacy of talaporfin PDT combined with olaparib for gastric cancer. MKN45, a gastric cancer cell line, was incubated with talaporfin, followed by irradiation, in the presence/absence of olaparib. Talaporfin PDT and olaparib exhibited excellent synergistic action in a concentration-dependent manner. PARP–DNA complexes were characterized based on bound chromatin using Western blot analyses. The combination of talaporfin PDT and olaparib enhanced PARP1 accumulation (the entrapment of PARP1–DNA complexes) in bound chromatin. The combination of talaporfin PDT and olaparib induced DNA double-strand breaks, which was confirmed by evaluating phosphorylated histone H2AX. Xenograft tumor mouse models were established, and antitumor effects were analyzed. In vivo, tumor growth was significantly suppressed following PDT with talaporfin and olaparib. Our results demonstrated that olaparib enhances the efficacy of talaporfin PDT by inducing the formation of PARP–DNA complexes. Therefore, our results suggest that the combination of talaporfin PDT and olaparib is a potential antitumor therapy for gastric cancer.

A novel fast kilovoltage switching dual-energy CT with deep learning [Deep learning based-spectral CT (DL-Spectral CT)], which generates a complete sinogram for each kilovolt using deep learning views that complement the measured views at each energy, was commercialized in 2020. The purpose of this study was to evaluate the accuracy of CT numbers in virtual monochromatic images (VMIs) and iodine quantifications at various radiation doses using DL-Spectral CT.Two multi-energy phantoms (large and small) using several rods representing different materials (iodine, calcium, blood, and adipose) were scanned by DL-Spectral CT at varying radiation doses. Images were reconstructed using three reconstruction parameters (body, lung, bone). The absolute percentage errors (APEs) for CT numbers on VMIs at 50, 70, and 100 keV and iodine quantification were compared among different radiation dose protocols.The APEs of the CT numbers on VMIs were15% in both the large and small phantoms, except at the minimum dose in the large phantom. There were no significant differences among radiation dose protocols in computed tomography dose index volumes of 12.3 mGy or larger. The accuracy of iodine quantification provided by the body parameter was significantly better than those obtained with the lung and bone parameters. Increasing the radiation dose did not always improve the accuracy of iodine quantification, regardless of the reconstruction parameter and phantom size.The accuracy of iodine quantification and CT numbers on VMIs in DL-Spectral CT was not affected by the radiation dose, except for an extremely low radiation dose for body size.

Background The Investigation of Stent Grafts in Aortic Dissection with extended length of follow-up trial showed that pre-emptive thoracic endovascular aneurysm repair (TEVAR) for the uncomplicated type B dissection (TBAD) in the subacute phase promotes aortic remodeling and avoids aortic-related death 5 years after onset. However, there are some patients with complete aortic remodeling (CAR) with optimal medical treatment (OMT) and severe complications after TEVAR such as retrograde type A dissection. Therefore, which patients should undergo pre-emptive TEVAR and optimal surgical timing are still under debate. We reported that aortic wall enhancement (AWE) after endovascular aneurysm repair for abdominal aortic aneurysm was associated with sac shrinkage. However, there is no report about the relationship between AWE and aortic dissection. Herein, we evaluated the relationship between AWE and acute TBAD. Methods From March 2012 to May 2018, consecutive patients with acute TBAD were retrospectively collected. We retrospectively analyzed 35 patients with acute TBAD who were treated with OMT and without pre-emptive TEVAR in the subacute phase. AWE was defined as an increase of more than 20 Hounsfield units in mean computed tomography (CT) values, comparing images in delayed contrast-enhanced scans with those in plain scans evaluated within 3 months from onset. The measurement points were all slices including the wall of the false lumen. The patients with traumatic dissection, type A dissection, acute complicated type B dissection, chronic (>12 weeks) dissection, and those lost to follow-up within 3 months from onset were excluded. The primary end point was spontaneous CAR under OMT, as determined by the latest contrast-enhanced CT scan. Results The median follow-up period from onset was 86 weeks and there were 25 cases (71.4%) with AWE. Under OMT, CAR was observed in 20 patients (57.1%); this was significantly associated with abdominal branch dissection (6/15 [40%] vs. 2/20 [10%], P = 0.050), number of tears more than 2 at onset (11/15 [73%] vs. 4/20 [20%], P = 0.003), multiple tears at 1 month after onset (9/15 [60%] vs. 4/20 [20%], P = 0.020), maximal false lumen diameter at 1 month after onset (14 vs. 8 mm, P = 0.025), and AWE within 3 months of onset (7/15 [47%] vs. 18/20 [90%], P = 0.010). Multivariate analysis demonstrated a significant difference with multiple tears at onset (P = 0.014) and AWE within 3 months of onset (P = 0.047). Conclusions AWE was associated with CAR under OMT for acute TBAD which is out of indication of pre-emptive TEVAR. Presence of AWE may be useful in predicting prognosis of TBAD.

Effects of endocrine disrupting chemicals (EDCs) on reproduction have not been fully explained comprehensively. In this study, we tried to validate the common effect of Bisphenol A (BPA) and Nonylphenol (NP) on the differentiation of embryonic stem (ES) cells and found that they modify the expression of germ cell specific genes. To elucidate functional significance on biological process, we performed Gene Ontology (GO)-based microarray analysis comparing with published GeneChip data of primordial germ cell development in vivo. Cluster analysis of gene expression profile revealed that EDC treatment and primordial germ cell (PGC) development shared characteristic cluster consists of GO terms related to "germ cell development" and "reproduction". In the GO term "reproduction", meiosis related genes showed high expression level by EDC exposure. These results suggest that BPA and NP affect not only some of the germ cell specific genes, but functionally interferes germ cell development and reproduction.

This study reports the first observed case of wild chimpanzees (Pan troglodytes) obtaining animal prey freshly killed by a sympatric leopard (Panthera pardus) and scavenging it with the leopard still nearby. This observation has important implications for the emergence of confrontational scavenging, which may have played a significant role in human evolution. Many scholars agree that eating meat became important during human evolution, and hominins first obtained meat by scavenging. However, it is debatable whether scavenging behavior was “passive” or “confrontational (power).” The latter is more dangerous, as it requires facing the original predator, and it is thus considered to have been important for the evolution of several human traits, including cooperation and language. Chimpanzees do scavenge meat, although rarely, but no previous evidence of confrontational scavenging has hitherto emerged. Thus, it was assumed that they are averse to confrontation with even leopard-sized predators. However, in the observed case the chimpanzees frequently emitted waa barks, which indicated that they were aware of the leopard's presence but they nevertheless continued to eat the scavenged meat. In addition, we compiled and reviewed 49 cases of chimpanzee encounters with animal carcasses in the Mahale Mountains of Tanzania in 1980–2017. Chimpanzees scavenged meat in 36.7% of these cases, and tended to eat the meat when it was fresh or if the animal species was usually hunted by chimpanzees. However, no evidence indicated that carcasses were avoided when leopard involvement was likely. These results suggest that chimpanzee-sized hominins could potentially confront and deprive leopard-size carnivores of meat., 野生チンパンジーがヒョウの獲物を食べることを初めて観察 --人類の祖先は肉食獣から獲物を奪っていたか--. 京都大学プレスリリース. 2019-04-16.

Objective The purpose of this study was to examine the relationship between the CT features of the primary-site gastric cancer and the concurrent existence or postoperative recurrence of hepatic metastasis. Materials and methods From January 2013 to July 2016, 125 patients with advanced gastric cancer who were evaluated by gastroscopy and contrast-enhanced CT at our institution were included. Eleven patients had hepatic metastasis at the time of diagnosis (synchronous hepatic metastasis). Five patients had hepatic recurrence after surgery (metachronous hepatic metastasis, median follow-up period of 313 days), and another 56 patients had no hepatic recurrence during follow-up period (negative hepatic metastasis, median follow-up period of 1102 days). Two radiologists independently reviewed the CT images and they determined the peak enhancement phase, and then measured the CT attenuation value of the gastric lesion for each phase. We compared the parameters of synchronous, metachronous and negative hepatic-metastasis. We calculated diagnostic performance of CT for diagnosing synchronous and metachronous hepatic metastasis. Results The peak enhancement was significantly diff ;erent between the three groups for both readers (reader 1, p = 0.0001; reader 2, p = 0.0002). Most of the synchronous and metachronous hepatic metastasis had peak enhancement in the arterial or portal phase. The CT attenuation values of synchronous and metachronous hepatic metastasis were significantly higher than those of negative hepatic metastasis in the delayed phase according to both readers (reader 1, p = 0.0003; reader 2, p = 0.0002). In predicting synchronous hepatic metastasis using peak enhancement, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 72.7%, 89.3%, 57.1%, 94.3%, and 86.6% for reader 1, and 54.5%, 94.6%, 66.7%, 91.4%, and 88.1% for reader 2. In predicting metachronous hepatic metastasis, the sensitivity, specificity, PPV, NPV, and accuracy were 60.0%, 89.3%, 33.0%, 94.3%, and 86.9% for reader 1, and 40.0%, 94.6%, 40.0%, 94.6%, and 90.2% for reader 2. Conclusion Our study showed that gastric cancer with synchronous and metachronous hepatic metastasis tends to show early enhancement with a washout pattern on contrast-enhanced CT. This feature would be helpful in image surveillance for synchronous or metachronous hepatic metastasis of gastric cancer.

Purpose To prospectively investigate the ability of amide proton transfer (APT) imaging, in comparison with that of diffusion-weighted imaging (DWI), to predict pathological factors in rectal cancer. Materials and methods Twenty-two patients who underwent MR examination including APT imaging and DWI for evaluation of rectal cancer were enrolled. APT signal intensity (SI) was defined as the magnetization transfer asymmetry at 3.5 ppm and was mapped. An apparent diffusion coefficient (ADC) map was generated using b-values of 0, 500 and 1000 s/mm2. APT SI and ADC were calculated by placing regions-of-interest in the tumors on these maps. Pathological factors including tumor size and tumor grade were also evaluated. Average APT SIs or ADCs were compared between the two groups classified based on each pathological factor using Student's t-test. Results The average APT SI of tumors with diameters of 5 cm or more (3.09 ± 1.41%) was significantly higher than that of tumors with diameters Conclusion Amide proton transfer imaging can predict tumor grade in rectal cancer.

The basement membrane zone consists of multiple components, including collagen XVII (COL17), which is the target of bullous pemphigoid. To our knowledge, no research has addressed the differences in basement membrane zone components between the skin and oral mucosa; therefore, we investigated the basement membrane zone proteins, with a focus on COL17. The mRNA and protein expression levels of COL17 were significantly higher in oral keratinocytes than in skin keratinocytes. Hemidesmosomal COL17 expression was markedly higher in oral keratinocytes than in skin keratinocytes, and its level was associated with adhesion strength. Oral keratinocytes adhered to the extracellular matrix more tightly than did skin keratinocytes in vitro. Based on these results, we attempt to explain the clinical diversity of bullous pemphigoid. COL17 depletion was more prominent in skin keratinocytes than in oral keratinocytes after treatment with COL17-NC16A mAbs, which have in vivo pathogenicity. COL17 C-terminus mAbs, which are not pathogenic, facilitated COL17 depletion in combination treatment with COL17-NC16A mAbs in both types of keratinocytes. In summary, the greater amount of COL17 in oral keratinocytes than in skin keratinocytes is associated with the higher strength of oral keratinocyte hemidesmosomal adhesion at the basement membrane zone. Our results may explain why bullous pemphigoid blistering tends to be more prevalent in the skin than in the oral mucosa.

Few patient-reported outcomes are available to measure the symptoms associated with malignant-related ascites in patient care and clinical research. Although the Edmonton Symptom Assessment System: Ascites Modification (ESAS:AM) is a brief tool to measure symptoms associated with malignant-related ascites, it remains to be fully validated.The objective of the study was to validate the ESAS:AM in Japanese cancer patients.We assessed the internal consistency, test-retest reliability, concurrent validity, and construct validity in 292 Japanese adult patients with cancer. They completed Japanese versions of the ESAS:AM, M.D. Anderson Symptom Inventory, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, and abdominal pain/ascites subscales of the EORTC Core Quality of Life Questionnaire, 26-item pancreatic cancer module.Cronbach's alpha coefficient of the ESAS:AM was 0.89. The intraclass correlation coefficient on test-retest examination of its total score was 0.93 (P 0.001). Pearson correlation coefficients of the total score of the ESAS:AM with the total score of the M.D. Anderson Symptom Inventory and abdominal pain/ascites subscales of the EORTC Core Quality of Life Questionnaire, 26-item pancreatic cancer module ranged from 0.44 to 0.81 (P 0.001) and those with global health status/quality of life and functional subscales of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 ranged from -0.40 to -0.61 (P 0.001). The total scores of the ESAS:AM were significantly higher in 20 patients with symptomatic ascites (34 [SD, 26]) than 267 patients without symptomatic ascites (23 [SD, 19]) (P = 0.018).The ESAS:AM is a reliable and valid tool for measuring symptoms associated with malignant-related ascites and can be used in daily patient care and future epidemiological studies and clinical trials.