Non-neuronal cholinergic system in regulation of immune function with a focus on α7 nAChRs

AbstractIn 1929, Dale and Dudley described the first reported natural occurrence of acetylcholine (ACh) in an animal’s body. They identified this ACh in the spleens of horses and oxen, which we now know suggests possible involvement of ACh in the regulation of lymphocyte activity and immune function. However, the source and function of splenic ACh were left unexplored for several decades. Recent studies on the source of ACh in the blood revealed ACh synthesis catalyzed by choline acetyltransferase (ChAT) in CD4+ T cells. T and B cells, macrophages and dendritic cells (DCs) all express all five muscarinic ACh receptor subtypes (mAChRs) and several subtypes of nicotinic AChRs (nAChRs), including α7 nAChRs. Stimulation of these mAChRs and nAChRs by their respective agonists causes functional and biochemical changes in the cells. Using AChR knockout mice, we found that M1/M5 mAChR signaling up-regulates IgG1 and pro-inflammatory cytokine production, while α7 nAChR signaling has the opposite effect. These findings suggest that ACh synthesized by T cells acts in an autocrine/paracrine fashion at AChRs on various immune cells to modulate immune function. In addition, an endogenous allosteric and/or orthosteric α7 nAChR ligand, SLURP-1, facilitates functional development of T cells and increases ACh synthesis via up-regulation of ChAT mRNA expression. SLURP-1 is expressed in CD205+ DCs residing in the tonsil in close proximity to T cells, macrophages and B cells. Collectively, these findings suggest that ACh released from T cells along with SLURP-1 regulates cytokine production by activating α7 nAChRs on various immune cells, thereby facilitating T cell development and/or differentiation, leading to immune modulation

ANGUSTIFOLIA3 Signaling Coordinates Proliferation between Clonally Distinct Cells in Leaves

SummaryCoordinated proliferation between clonally distinct cells via inter-cell-layer signaling largely determines the size and shape of plant organs [1–4]. Nonetheless, the signaling mechanism underlying this coordination in leaves remains elusive because of a lack of understanding of the signaling molecule (or molecules) involved. ANGUSTIFOLIA3 (AN3, also called GRF-INTERACTING FACTOR1) encodes a putative transcriptional coactivator with homology to human synovial sarcoma translocation protein [5–7]. AN3 transcripts accumulate in mesophyll cells but are not detectable in leaf epidermal cells [8]. However, we found here that in addition to mesophyll cells [5, 6], epidermal cells of an3 leaves show defective proliferation. This spatial difference between the accumulation pattern of AN3 transcripts and an3 leaf phenotype is explained by AN3 protein movement across cell layers. AN3 moves into epidermal cells after being synthesized within mesophyll cells and helps control epidermal cell proliferation. Interference with AN3 movement results in abnormal leaf size and shape, indicating that AN3 signaling is indispensable for normal leaf development. AN3 movement does not require type II chaperonin activity, which is needed for movement of some mobile proteins [9]. Taking these findings together, we present a novel model emphasizing the role of mesophyll cells as a signaling source coordinating proliferation between clonally independent leaf cells

A Case of Liposarcoma With Peritonitis Due to Jejunal Perforation

A 21-year-old man, who had been treated for congenital dilatation of the bile duct 13 years previously, presented with an acute abdomen. The physical examination suggested peritonitis, and an emergent laparotomy was performed. A perforation was foundin the jejunum approximately 100 cm distal to the ligament of Treitz, followed by resection of a 60-cm jejunal segment. No tumorous lesions were found during the operation, and the resected jejunal segment showed only focal myxomatous thickening of the serosa. Despite intensive therapy, he died of uncontrollable septic shock 2 days after the operation. Unexpectedly, however, histological examination revealed a liposarcoma, showing an unclassifiable histology. From the distribution of the lesion and the histological findings, it is thought that a primary lesion was somewhere else, covered by severe adhesions due to the previous operation, and that the tumor cells spreading from it could have caused the jejunal perforation through vascular involvement. Although extremely rare, liposarcomas in the abdomen can cause intestinal perforation. It is important for both clinicians andpathologists to carefully investigate the cause of an unusual clinical presentation such as intestinal perforation

Experimental Study on Structural Behaviour of Steel Wire Mesh under Impact Loading

In view of application to debris flow/rockfall barrier system, several types of steel wire mesh were selected to verify their basic behaviour under impact load of free fall weight at the controlled testing environment at an in-house testing facility capable of dropping a heavy weight on approximately 1-meter square panel made of such steel wire mesh material. Out of the 3 types of wire mesh tested, high-performance chain link endured the highest impact load energy, while newly developed wire mesh showed a high potential of effectively absorbing the impact energy by its plastic deformation along the total length of wire components. Both of the above two types of wire mesh are expected to be applied in flexible type debris flow catchment system in combination with larger opening mesh such as ring net. The newly developed wire mesh consisting of spirally deformed steel wires behaved as energy-absorbing elements while transmitting the impact load to the supporting ropes by its own plastic deformation along the total wire length

Impairment of bimanual in-phase movement during recovery from frontal lobe tumor surgery: a case report

The mechanisms underlying bimanual coordination have not yet been fully elucidated. Here, we evaluated the clinical features of bimanual movement impairment in a patient following surgery for a frontal lobe tumor. The patient was an 80-year-old man who had undergone subtotal tumor resection for a tumor in the right superior frontal gyrus. Histological examination of the resected specimen led to the diagnosis of malignant lymphoma of the diffuse large B-cell type, and the patient subsequently received high-dose methotrexate-based chemotherapy. Postoperatively, the patient had difficulty with bimanual movement, and on the 5th postoperative day we found that the impairment could not be attributed to weakness. Temporal changes in the characteristics of manual movements were analyzed. Bimanual diadochokinesis (opening/closing of the hands, pronation/supination of the forearms, and sequential finger movements) was more disturbed than unilateral movements; in-phase movements were more severely impaired than anti-phase movements. Bimanual movement performance was better when cued using an auditory metronome. On the 15th postoperative day, movements improved. The present observations show that in addition to the disturbance of anti-phase bimanual movements, resection of the frontal lobe involving the supplementary motor area (SMA) and premotor cortex (PMC) can cause transient impairment of in-phase bimanual diadochokinesis, which can be more severe than the impairment of anti-phase movements. The effect of auditory cueing on bimanual skills may be useful in the diagnosis of anatomical localization of the superior frontal gyrus and functional localization of the SMA and PMC and in rehabilitation of patients with brain tumors, as in the case of degenerative movement disorders

Long-term Survival of a Case of Rectal Neuroendocrine Carcinoma with Liver Metastasis

Colorectal neuroendocrine carcinoma（NEC）is extremely rare and has a dismal prognosis. However, no standardized treatment strategy has been established for this lesion. For patients with NEC and distant metastasis, disease stabilization is difficult even after treatment with multidisciplinary strategies including chemotherapy. Here we describe a case of rectal NEC that presented as multiple liver metastases; a favorable prognosis was obtained after treatment with a multidisciplinary strategy that included surgery, irradiation, and chemotherapy. A 66-year-old male presented with diarrhea and constipation. Colonoscopy and a computed tomography（CT）scan revealed a rectal mass involving all of the luminal circumference, after which a diagnosis of NEC was confirmed by pathological examination. A CT scan also revealed several liver metastases in S5, S6, and S8. Abdominoperineal resection with total mesenteric excision and lymphadenectomy, including the lateral area, was performed. After resection, we administered radiation for local disease control in the lateral area. We also administered chemotherapy consisting of cisplatin and irinotecan for the liver metastases because only the endocrine cell component constituted this tumor. After chemotherapy, a CT scan was performed to confirm that the liver metastasis in S5 and S6 had disappeared, and it was shown that the other lesion in S8 had shrunk substantially（it eventually disappeared）. Then, 48 months after resection, all metastatic liver tumors were under good control, and no other recurrent lesion was recognized. In conclusion, a multidisciplinary strategy including optimal chemotherapy seems to be important to achieve a favorable prognosis of NEC of the colorectum with distant metastasis

Contrast-enhanced harmonic endoscopic ultrasound using time–intensity curve analysis predicts pathological grade of pancreatic neuroendocrine neoplasm

PURPOSE: Histological grading is important for the treatment algorithm in pancreatic neuroendocrine neoplasms (PNEN). The present study examined the efficacy of contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) and time-intensity curve (TIC) analysis of PNEN diagnosis and grading. METHODS: TIC analysis was performed in 30 patients using data obtained from CH-EUS, and a histopathological diagnosis was made via EUS-guided fine-needle aspiration or surgical resection. The TIC parameters were analyzed by dividing them into G1/G2 and G3/NEC groups. Then, patients were classified into non-aggressive and aggressive groups and evaluated. RESULTS: Twenty-six patients were classified as G1/G2, and four as G3/NEC. From the TIC analysis, five parameters were obtained (I: echo intensity change, II: time for peak enhancement, III: speed of contrast, IV: decrease rate for enhancement, and V: enhancement ratio for node/pancreatic parenchyma). Three of these parameters (I, IV, and V) showed high diagnostic performance. Using the cutoff value obtained from the receiver-operating characteristic (ROC) analysis, the correct diagnostic rates of parameters I, IV, and V were 96.7%, 100%, and 100%, respectively, between G1/G2 and G3/NEC. A total of 21 patients were classified into the non-aggressive group, and nine into the aggressive group. Using the cutoff value obtained from the ROC analysis, the accurate diagnostic rates of I, IV, and V were 86.7%, 86.7%, and 88.5%, respectively, between the non-aggressive and aggressive groups. CONCLUSION: CH-EUS and TIC analysis showed high diagnostic accuracy for grade diagnosis of PNEN. Quantitative perfusion analysis is useful to predict PNEN grade diagnosis preoperatively

Endoscopic ultrasonography findings of pancreatic parenchyma for predicting subtypes of intraductal papillary mucinous neoplasms

Background and Aims: The subtypes of intraductal papillary mucinous neoplasms (IPMNs) are closely associated with the clinicopathological behavior and recurrence after surgical resection. However, there are no established non-invasive methods to confirm the subtypes of IPMNs without surgery. The aim of this study is to predict the subtypes of IPMNs using the findings of endoscopic ultrasonography (EUS). Methods: Sixty-two consecutive patients with IPMNs who underwent EUS before surgery were retrospectively reviewed. The following EUS findings were analyzed and their relationship with the subtypes was evaluated: diameter of the main pancreatic duct, cyst size, number of cysts, height of mural nodule, early chronic pancreatitis (CP) finding, fatty parenchyma and atrophic parenchyma. Results: The subtypes of IPMNs were as follows: gastric (G)-type 38 (61%), intestinal (I) -type 14 (23%) and pancreatobiliary (PB) -type 10 (16%). Fatty parenchyma was significantly associated with G-type (P Conclusions: The evaluation of EUS findings, especially focused on the pancreatic parenchyma, has the potential to predict the subtypes of IPMN

For Vol.70, No.5 pp405-408 A Multicenter, Prospective, Randomized Controlled Trial Evaluating the Efficacy of Rectal Diclofenac and Sublingual Nitrate as a Combined Prophylactic Treatment for Post-ERCP Pancreatitis

In the article by Tomoda T et al. entitled “A Multicenter, Prospective, Randomized Controlled Trial Evaluating the Efficacy of Rectal Diclofenac and Sublingual Nitroglycerin as a Combined Prophylactic Treatment for Post-ERCP Pancreatitis”, which appeared in the October 2016 issue, Vol. 70, No. 5, pp405-408, the word “nitroglycerin” should be corrected to “nitrate” throughout the manuscript

Utility of Endoscopic Ultrasound-Guided Fine Needle Aspiration in the Diagnosis of Local Recurrence of Pancreaticobiliary Cancer after Surgical Resection

Background/Aims: Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA; EUS-FNA) allows for diagnostic tissue specimens from various regions to be analyzed. However, diagnosing recurrent pancreaticobiliary cancer after surgery is sometimes difficult. We evaluated the efficacy of EUS-FNA in the diagnosis of local recurrence of pancreaticobiliary cancer and analyzed the factors associated with falsenegative results. Methods: Fifty-one consecutive patients who underwent EUS-FNA due to suspected recurrence of pancreaticobiliary cancer after surgery in an academic center were retrospectively analyzed. The criteria for EUS-FNA were a resected margin or remnant pancreas mass, round swollen lymph node (≥10 mm in diameter), and soft-tissue enhancement around a major artery. Patients with suspected liver metastasis or malignant ascites were excluded. Results: Thirty-nine of the 51 patients had pancreatic cancer; the remaining 12 had biliary cancer. The target sites for EUS-FNA were the soft tissue around a major artery (n=22, 43%), the resected margin or remnant pancreas (n=12, 24%), and the lymph nodes (n=17, 33%). The median size of the suspected recurrent lesions was 15 mm (range, 8 to 40 mm). The overall sensitivity, specificity and accuracy of EUS-FNA for the diagnosis of recurrence was 84% (32/38), 100% (13/13), and 88% (45/51), respectively. FNA of the soft tissue around major arteries (odds ratio, 8.23; 95% confidence interval, 1.2 to 166.7; p=0.033) was significantly associated with a falsenegative diagnosis in the multivariate analysis. Conclusions: EUS-FNA is useful for diagnosing recurrent cancer, even after pancreaticobiliary surgery. The diagnoses of recurrence at soft-tissue sites should be interpreted with caution