The Japan Monkey Centre Primates Brain Imaging Repository of high-resolution postmortem magnetic resonance imaging: the second phase of the archive of digital records

超高磁場MRIで見る霊長類「全脳」神経回路の多様性 --分野横断型の霊長類脳標本画像リポジトリ：ヒト脳と精神・神経疾患の理解を加速する国際研究基盤--. 京都大学プレスリリース. 2023-05-22.A comparison of neuroanatomical features of the brain between humans and our evolutionary relatives, nonhuman primates, is key to understanding the human brain system and the neural basis of mental and neurological disorders. Although most comparative MRI studies of human and nonhuman primate brains have been based on brains of primates that had been used as subjects in experiments, it is essential to investigate various species of nonhuman primates in order to elucidate and interpret the diversity of neuroanatomy features among humans and nonhuman primates. To develop a research platform for this purpose, it is necessary to harmonize the scientific contributions of studies with the standards of animal ethics, animal welfare, and the conservation of brain information for long-term continuation of the field. In previous research, we first developed a gated data-repository of anatomical images obtained using 9.4-T ex vivo MRI of postmortem brain samples from 12 nonhuman primate species, and which are stored at the Japan Monkey Centre. In the present study, as a second phase, we released a collection of T2-weighted images and diffusion tensor images obtained in nine species: white-throated capuchin, Bolivian squirrel monkey, stump-tailed macaque, Tibet monkey, Sykes’ monkey, Assamese macaque, pig-tailed macaque, crested macaque, and chimpanzee. Our image repository should facilitate scientific discoveries in the field of comparative neuroscience. This repository can also promote animal ethics and animal welfare in experiments with nonhuman primate models by optimizing methods for in vivo and ex vivo MRI scanning of brains and supporting veterinary neuroradiological education. In addition, the repository is expected to contribute to conservation, preserving information about the brains of various primates, including endangered species, in a permanent digital form

Adalimumab Treatment in Biologically Naïve Crohn’s Disease: Relationship with Ectopic MUC5AC Expression and Endoscopic Improvement

Background. Adalimumab (ADA) is effective for patients with Crohn’s disease (CD). However, there have been few reports on ADA therapy with respect to its relationship with pathologic findings and drug efficacy in biologically naïve CD cases. Methods. Fifteen patients with active biologically naïve CD were treated with ADA. We examined them clinically and pathologically with ectopic MUC5AC expression in the lesions before and after 12 and 52 weeks of ADA therapy, retrospectively. Results. Both mean CD activity index scores and serum C-reactive protein values were significantly lower after ADA therapy (P<0.001). In the MUC5AC negative group, all cases exhibited clinical remission (CR) and endoscopic improvement at 52 weeks. In MUC5AC positive groups, loss of MUC5AC expression was detected in cases having CR and endoscopic improvement at 52 weeks, while remnant ectopic MUC5AC expression was observed in those exhibiting no endoscopic improvement and flare up after 52 weeks. Conclusions. ADA leads to CR and endoscopic improvement in biologically naïve CD cases. In addition, ectopic MUC5AC expression may be a predictive marker of flare up and endoscopic improvement in the intestines of CD patients

Subset Analysis of a Multicenter, Randomized Controlled Trial to Compare Magnifying Chromoendoscopy with Endoscopic Ultrasonography for Stage Diagnosis of Early Stage Colorectal Cancer

<div><p>Background</p><p>Our recent prospective study found equivalent accuracy of magnifying chromoendoscopy (MC) and endoscopic ultrasonography (EUS) for diagnosing the invasion depth of colorectal cancer (CRC); however, whether these tools show diagnostic differences in categories such as tumor size and morphology remains unclear. Hence, we conducted detailed subset analysis of the prospective data.</p><p>Methods</p><p>In this multicenter, prospective, comparative trial, a total of 70 patients with early, flat CRC were enrolled from February 2011 to December 2012, and the results of 66 lesions were finally analyzed. Patients were randomly allocated to primary MC followed by EUS or to primary EUS followed by MC. Diagnoses of invasion depth by each tool were divided into intramucosal to slight submucosal invasion (invasion depth <1000 μm) and deep submucosal invasion (invasion depth ≥1000 μm), and then compared with the final pathological diagnosis by an independent pathologist blinded to clinical data. To standardize diagnoses among examiners, this trial was started after achievement of a mean κ value of ≥0.6 which was calculated from the average of κ values between each pair of participating endoscopists.</p><p>Results</p><p>Both MC and EUS showed similar diagnostic outcomes, with no significant differences in prediction of invasion depth in subset analyses according to tumor size, location, and morphology. Lesions that were consistently diagnosed as Tis/T1-SM_S or ≥T1-SM_D with both tools revealed accuracy of 76–78%. Accuracy was low in borderline lesions with irregular pit pattern in MC and distorted findings of the third layer in EUS (MC, 58.5%; EUS, 50.0%).</p><p>Conclusions</p><p>MC and EUS showed the same limited accuracy for predicting invasion depth in all categories of early CRC. Since the irregular pit pattern in MC, distorted findings to the third layer in EUS and inconsistent diagnosis between both tools were associated with low accuracy, further refinements or even novel methods are still needed for such lesions.</p><p>Trial Registration</p><p>University hospital Medical Information Network Clinical Trials Registry UMIN <a href="https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000006045&language=E" target="_blank">000005085</a></p></div

The profile of lipid metabolites in urine of marmoset wasting syndrome.

Marmoset wasting syndrome (MWS) is clinically characterized by progressive weight loss. Although morbidity and mortality of MWS are relatively high in captive marmosets, its causes remain unknown. Lipid mediators are bioactive metabolites which are produced from polyunsaturated fatty acids, such as arachidonic acid (AA) and eicosapentaenoic acid. These lipid metabolites regulate a wide range of inflammatory responses and they are excreted into the urine. As urinary lipid profiles reflect systemic inflammatory conditions, we comprehensively measured the levels of 141 types of lipid metabolites in the urines obtained from healthy common marmoset (Callithrix jacchus) (N = 7) or marmosets with MWS (N = 7). We found that 41 types of metabolites were detected in all urine samples of both groups. Among them, AA-derived metabolites accounted for 63% (26/41 types) of all detected metabolites. Notably, the levels of AA-derived prostaglandin (PG) E2, PGF2α, thromboxane (TX) B2 and F2-isoprostanes significantly increased in the urine samples of marmosets with MWS. In this study, we found some urinary lipid metabolites which may be involved in the development of MWS. Although the cause of MWS remains unclear, our findings may provide some insight into understanding the mechanisms of development of MWS

Subset analysis according to tumor size.

<p>^#1 χ² test</p><p>^#2 Fisher’s exact probability test. Tis/T1-SM_S, mucosal to submucosal cancer with invasion depth <1000 μm; T1-SM_D, submucosal cancer with submucosal invasion depth ≥1000 μm.</p><p>Subset analysis according to tumor size.</p

Detailed diagnostic findings of MC and EUS.

<p>Tis/T1-SM_S, mucosal to submucosal cancer with invasion depth <1000 μm; T1-SM_D, submucosal cancer with submucosal invasion depth <b>≥</b>1000 μm.</p

Subset analysis according to tumor morphology.

<p>^#1 χ² test</p><p>^#2 Fisher’s exact probability test. Tis/T1-SM_S, mucosal to submucosal cancer with invasion depth <1000 μm; T1-SM_D, submucosal cancer with submucosal invasion depth ≥1000 μm.</p><p>Subset analysis according to tumor morphology.</p

Representative images of difficult lesion for diagnosis.

<p><b>A-D)</b> A case of rectal cancer for which diagnosis between magnifying chromoendoscopy (MC) and endoscopic ultrasonography (EUS) was consistent, but incorrect. <b>A)</b> Conventional endoscopic view using white-light imaging (WLI) reveals a type 0-IIa+IIc tumor, 10 mm in size. <b>B)</b> MC shows a non-structural pit pattern (type V_N), defined as ≥T1-SM_D. <b>C)</b> EUS shows a hypoechoic mass disrupting the third layer, defined as ≥T1-SM_D. <b>D)</b> Hematoxylin and eosin (HE) staining of the resected specimens shows well-differentiated adenocarcinoma limited to the mucosal layer (pTis) and dense lymphoid follicles in the submucosal layer (×20). No evidence of lymphovascular invasion is seen. <b>E-H)</b> A case of sigmoid colon cancer for which diagnosis between MC and EUS was inconsistent, with MC proving correct. <b>E)</b> Conventional endoscopic view using WLI reveals type 0-IIa tumor, 20 mm in size. <b>F)</b> MC shows a low-grade, irregular, branched pit pattern (type V_I-L), defined as Tis/T1-SM_S. <b>G)</b> EUS shows a hypoechoic area that clearly invades into the third layer, defined as ≥T1-SM_D. <b>H)</b> HE staining for resected specimens shows well-differentiated tubular adenocarcinoma, mostly limited to mucosal invasion, but submucosal invasive gland (black arrow) was observed with surrounding lymphoid infiltration (×20). The vertical depth of invasion into the submucosa is 250 μm, defined as pT1-SM_S. There is no evidence of lymphovascular invasion. <b>I-L)</b> A case of rectal cancer for which diagnosis between MC and EUS was inconsistent, with EUS proving correct. <b>I)</b> Conventional endoscopic view using WLI reveals a type 0-IIa tumor, 20 mm in size. <b>J)</b> MC partially shows a non-structural pit pattern (type V_N) surrounded by a high-grade irregular pit pattern (type V_I-H), defined as ≥T1-SM_D. <b>K)</b> A hypoechoic area on EUS is confined to the first and second layers, with conservation of the third layer, defined as Tis/T1-SM_S. <b>L)</b> HE staining for resected specimens shows well-differentiated tubular adenocarcinoma, mostly limited to mucosal invasion with submucosal infiltration in a small part (black arrow) (×20). There is no evidence of lymphovascular invasion. The vertical depth of invasion into the submucosa is 500 μm, defined as pT1-SM_S. There is no evidence of lymphovascular invasion.</p

Results according to diagnosis by MC and EUS.

<p>Tis/T1-SM_S, mucosal to submucosal cancer with invasion depth <1000 μm; T1-SM_D, submucosal cancer with submucosal invasion depth ≥1000 μm.</p