Glutamate hypothesis in schizophrenia

Schizophrenia is a chronic and severe psychiatric disorder that has profound impact on an individual’s life and on society. Thus, developing more effective therapeutic interventions is essential. Over the past quarter‐century, an abundance of evidence from pharmacologic challenges, post‐mortem studies, brain imaging, and genetic studies supports the role of glutamatergic dysregulation in the pathophysiology of schizophrenia, and the results of recent randomized clinical trials based on this evidence have yielded promising results. In this article, we review the evidence that alterations in glutamatergic neurotransmission, especially focusing on the N‐methyl‐d ‐aspartate receptor (NMDAR) function, may be a critical causative feature of schizophrenia, how this contributes to pathologic circuit function in the brain, and how these insights are revealing whole new avenues for treatment development that could reduce treatment‐resistant symptoms, which account for persistent disability.     

Generalized sarcoidlike granulomas with systemic angiitis, crescentic glomerulonephritis, and pulmonary hemorrhage. Report of an autopsy case

A 19-year-old woman showed rapidly progressive renal and respiratory failure and died after a short clinical course. The autopsy revealed that death was due to crescentic glomerulonephritis and pulmonary hemorrhage. The intrathoracic lymph nodes, lungs, kidneys, and other organs contained numerous epithelioid granulomas, some of which had foci of central coagulative necrosis. The aorta, its major branches, and small- to medium-sized vessels of various organs also had multiple areas of granulomatous angiitis. This is, to our knowledge, the first report of such autopsy findings. A discussion of the etiopathogenesis of the disease is presented.     

Extracellular vesicles released from irradiated neonatal mouse cheek tissue increased cell survival after radiation

Alopecia is one of the common symptoms after high-dose radiation exposure. In our experiments, neonatal mice that received 7 Gy X-ray exhibited defects in overall hair growth, except for their cheeks. This phenomenon might suggest that some substances were secreted and prevented hair follicle loss in the infant tissues around their cheeks after radiation damage. In this study, we focused on exosome-like vesicles (ELV) secreted from cheek skin tissues and back skin tissues, as control, and examined their radiation protective effects on mouse fibroblast cell lines. We observed that ELV from irradiated cheek skin showed protective effects from radiation. Our results suggest that ELV from radiation-exposed cheek skin tissue is one of the secreted factors that prevent hair follicle loss after high-dose radiation.     

An autopsy case of thymic carcinoma producing various tumor markers and the examination of 222 autopsy cases of thymic malignant tumor in Japan

The autopsy of a 76-year-old Japanese female patient, which revealed thymic carcinoma with various tumor markers such as NSE, CYFRA, and CA-125, is presented. The patient died from hepatic failure because the liver was overtaken by the tumors. At autopsy, the thymic carcinoma was found to have metastased only in the liver. From microscopical analyses and electron microscopical findings, we diagnosed poorly differenciated squamous cell carcinoma of thymic origin. In the histochemical analyses, the tumor cells were positively stained in CA 125, CA 19-9, EMA, NSE, AE 1, AE 3, CEA, S-100, glimerius and Bcl-2. These date suggest that the tumor cells produced various tumor markers. In 222 autopsy cases of thymic malignant tumor observed in Japan over a period of 4 years, the dominant pathohistological image was squamous cell carcinoma. It is interesting that the greatest number of combined malignant tumors with thymic malignancies were thyroid papillary carcinomas.     

Spread of lymph node metastasis and adjuvant therapy for distal cholangiocarcinoma

International Journal of Clinical Oncology - Lymphatic metastasis is a major route of metastasis in distal cholangiocarcinoma (DCC). The present study aimed to elucidate the pattern of lymph node...     

Cytotoxic antimelanoma drugs suppress the activation of M2 macrophages

Together with regulatory T cells (Tregs), tumor‐associated macrophages (TAMs) play roles in maintaining the tumor microenvironment. Although cytotoxic antimelanoma drugs such as dacarbazine (DTIC), nimustine hydrochloride (ACNU) and vincristine (VCR) have been used for the treatment of malignant melanoma as adjuvant therapy in Japan, the detailed mechanisms of their immunomodulatory effects are not fully understood. As the majority of TAMs are alternatively activated M2 macrophages that favour tumor development, the aim of this study was to elucidate the immunomodulatory effects of these reagents on human monocyte‐derived M2 macrophages. First, mRNA expressions and protein production of immune checkpoint molecules, PD‐L1 and chemokines by CD163⁺ CD206⁺ M2 macrophages derived from peripheral blood mononuclear cells were investigated to determine the immunomodulatory effects of DTIC, ACNU, and VCR. DTIC and VCR significantly decreased PD‐L1 mRNA expression, which was confirmed by flow cytometry. Moreover, the mRNA expression and production of CCL22 were significantly decreased by DTIC, which suggested that DTIC might suppress the recruitment of Tregs in the tumor site. Furthermore, the decreased expression of PD‐L1 and production of CCL22 were validated in vivo, using the B16F10 mouse melanoma model, leading to abrogation of the suppressive function of T‐cell proliferation. The present report suggests one of the possible antimelanoma mechanisms of DAV combination chemotherapy for melanoma patients.     

Rare presentation of De Garengeot hernia treated by transabdominal preperitoneal hernia repair: A case report

We present a rare case of De Garengeot hernia treated with simultaneous laparoscopic appendectomy and transabdominal preperitoneal hernia repair. Our patient was an 85-year-old man with a bulging mass in the right groin. De Garengeot hernia was observed on contrast-enhanced CT. Urgent laparoscopy showed the distal part of the appendix passing through a right-sided femoral hernia. Laparoscopic appendectomy was performed, followed by transabdominal preperitoneal repair of the femoral hernia. Pathological examination revealed ischemic necrosis of the appendix. The patient's postoperative recovery was uneventful.     

Relationship between joint motion and acceleration during single-leg standing in healthy male adults

[Purpose] The purpose of this study was to clarify the relationship between acceleration and joint movement by synchronizing accelerometers and a three-dimensional motion analysis system, and to show the utility of an accelerometer as a postural control assessment tool. [Subjects and Methods] Head, lumbar, shank accelerations and various joint angles during single-leg standing were measured of 20 healthy males. Root mean squares of acceleration and joint angle were calculated. Fast Fourier transform analysis was performed for head, lumbar, and shank accelerations, and the median frequencies were calculated. Then, principal component analysis was performed for the median frequency of each acceleration. Stepwise multiple regression analysis was also used to examine the relationship between joint angle and acceleration. [Results] The score of the first principal component was highest for shank acceleration, while that of the second principal component was highest for lumbar and head accelerations. In multiple regression analysis, hip flexion/extension and adduction/abduction were identified as variables associated with head acceleration. [Conclusion] We were able to confirm the aggregation of acceleration into two components, which we interpreted as postural control strategies using primarily the ankle and hip joints. Furthermore, though multiple regression analysis, we were able to clarify the joint movement indicated by acceleration of each segment.Key words: Postural control, Acceleration, Ankle sprain