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Polyneuropathy, Organomegaly, Endocrinopathy, M-protein and Skin changes (POEMS) syndrome manifests as elevated levels of vascular endothelial growth factor (VEGF) and monoclonal gammopathy. We treated a case of POEMS syndrome showing monoclonality in both IgA-λ and IgG-κ. Serial renal biopsies before treatment and after normalization of the VEGF levels suggested that glomerular microangiopathy had developed due to VEGF, while biclonal gammopathy was not eliminated. The renal pathology, proteinuria, and renal function all clearly improved. Although severe polyneuropathy limited activities of daily living and enforced a bedridden state, the patient dramatically regained his motor function, achieving crutch walking after induction of remission. This case is highly notable due to the presence of biclonality and repeated biopsies.

Yo Shimizu,1 Tsuyoshi Tsukada,2 Hiromi Sakata-Haga,2 Daisuke Sakai,3 Hiroki Shoji,3 Yutaka Saikawa,1 Toshihisa Hatta2 1Department of Pediatrics, Kanazawa Medical University, Uchinada, Ishikawa, Japan; 2Department of Anatomy, Kanazawa Medical University, Uchinada, Ishikawa, Japan; 3Department of Biology, Kanazawa Medical University, Uchinada, Ishikawa, JapanCorrespondence: Toshihisa HattaDepartment of Anatomy, Kanazawa Medical University, Uchinada, Ishikawa, JapanTel +81-76-281-8113Fax +81-76-218-8189Email thatta@kanazawa-med.ac.jpBackground: A number of childhood diseases have been identified, such as severe infection or autoinflammatory disease, in which immune overreaction against inflammation is a possible underlying mechanism. Previous reports have demonstrated that fetal cells exposed to maternal immune activation (MIA) induced by polyriboinosinic-polyribocytidylic acid [poly(I:C)] exhibited hypersensitivity to inflammation in vitro. However, the details of this mechanism remain unclear. Therefore, this study aimed to reveal the reaction to inflammation in offspring exposed to MIA in the prenatal period, as well as its molecular mechanism, using a viral infection mouse model.Materials and Methods: Pregnant mice at 12.5, 14.5, and 16.5 days post coitum were injected intraperitoneally with poly(I:C) 20 mg/kg body weight (BW) or saline. Offspring aged 3– 4 weeks received the second injection of 20 mg/kg BW or 4 mg/kg BW poly(I:C) or saline. Serum and tissues were collected at 2, 24, 48, and 72 h after the postnatal injection. The cytokine profile, histopathology of organs, and unfolded protein response (UPR) in offspring were examined.Results: The serum levels of interleukin (IL)-6, IL-17, and interferon-γ were significantly higher in the MIA group, and acute liver necrosis was detected. Moreover, failure in UPR was observed in the MIA group compared with that in the control group.Conclusion: Overall, MIA exposure in utero caused failure in UPR as well as immune overreaction to the second attack of inflammation in offspring. Our results suggested that prenatal exposure to MIA might contribute to the congenital inflammatory constitution after birth.Keywords: maternal immune activation, liver necrosis, immune overreaction, unfolded protein response defects

A 17-year-old man received continuous ambulatory peritoneal dialysis (CAPD) catheter implantation and had started peritoneal dialysis. Perfusion failure of peritoneal dialysis catheter occurred one month after the catheter implantation. Transcatheter contrast examination revealed catheter obstruction about 4-5 cm from the catheter tip. We performed reduced port surgery to remove the obstruction. Laparoscopy revealed that the omentum was adhered to the abdominal wall and wrapped the catheter. We diagnosed the cause of catheter malfunction as omentum wrapping. We removed the omentum from the catheter, and repositioned the catheter into the Douglas fossa. Although CAPD worked successfully after the operation, perfusion failure recurred one month after the operation. The patient requested discontinuation of CAPD and change to hemodialysis. Therefore, we removed the CAPD catheter. The catheter was adhered to the omentum. Reduced port surgery for peritoneal dialysis catheter obstruction has the advantage of being minimally invasive and is a reliable procedure, but further studies are needed to reduce the recurrence rate of perfusion failure and to establish the procedure after perfusion failure.

MC5R is known for its role in the exocrine function of sebaceous glands, but other functions in the epidermis remain unclear. This study focused on the relationship between MC5R and homeostasis in the epidermis and examined the role of MC5R in mice whose skin was irradiated with UVB waves. UVB irradiation-induced skin ulcers and severe inflammation at lower doses in homozygotes of MC5R-deficient (i.e., MC5R−/−) mice (150 mJ/cm2) than the doses in wild-type mice (500 mJ/cm2). Transepidermal water loss was increased (approximately 10-fold) in adult MC5R−/− mice compared with that in wild-type mice. In neonates, a dye exclusion assay showed no remarkable difference between MC5R−/− and wild-type mice. After UVB irradiation, compared with wild-type mice, MC5R−/− mice showed increased inflammatory cell infiltration in the dermis of the ulcerative region, significantly increased thickness of the epidermis in the nonulcerative region, significantly more prickle cells in the nonulcerative region, and increased serum IL-6 levels but decreased IL-10 levels. Transmission electron microscopy revealed fewer lamellar granules, less lipid secretion, and an expansion of the trans-Golgi network in the epidermis in MC5R−/− mice. This study elucidated the increased sensitivity to UVB irradiation and decreased barrier function in MC5R−/−mice., Graphical abstract

In rodent models, leukemia inhibitory factor (LIF) is involved in cerebral development via the placenta, and maternal immune activation is linked to psychiatric disorders in the child. However, whether LIF acts directly on neural progenitor cells (NPCs) remains unclear. This study performed DNA microarray analysis and quantitative RT-PCR on the fetal cerebrum after maternal intraperitoneal or fetal intracerebral ventricular injection of LIF at day 14.5 (E14.5) and determined that the expression of insulin-like growth factors (IGF)-1 and -2 was induced by LIF. Physiological IGF-1 and IGF-2 levels in fetal cerebrospinal fluid (CSF) increased from E15.5 to E17.5, following the physiological surge of LIF levels in CSF at E15.5. Immunostaining showed that IGF-1 was expressed in the cerebrum at E15.5 to E19.5 and IGF-2 at E15.5 to E17.5 and that IGF-1 receptor and insulin receptor were co-expressed in NPCs. Further, LIF treatment enhanced cultured NPC proliferation, which was reduced by picropodophyllin, an IGF-1 receptor inhibitor, even under LIF supplementation. Our findings suggest that IGF expression and release from the NPCs of the fetal cerebrum in fetal CSF is induced by LIF, thus supporting the involvement of the LIF–IGF axis in cerebral cortical development in an autocrine/paracrine manner.

We developed a non-destructive and rapid whole-mount bone staining method for small fish, Xenopus laevis, and rodent fetuses (RAP-B). RAP-B does not require skin or soft tissue removal. However, RAP-B requires hair removal from hairy animals, such as adult mice and rats. In the present study, we investigated hair removal chemical treatments that did not result in soft tissue destruction. The hair removal effectiveness was investigated using a calcium mercaptoacetate or sodium mercaptoacetate solution on skin fragments obtained from the back of adult mice. A mixture of 2% sodium mercaptoacetate in 3% potassium hydroxide was found to be the most effective in complete hair removal from the skin. Using this hair removal treatment as a pretreatment for RAP-B, the preparation of fast-acting artifact-free whole-mount bone staining was possible without skin and soft tissue removal (RAP-B/HR). We performed a seamless observation from a low magnification wide-view to a high magnification without artifactacting artifacts using fluorescence zoom microscopy. Therefore, the combination of RAP-B/HR and fluorescent zoom microscopy is a novel platform for three-dimensional, wide-field, high-resolution pathological anatomical analysis.

The authors show the mechanism behind the formation of columnar patters in directional quenching and elucidate the role of confinement in the fluctuations at the interface.

Here we propose a new protocol for whole-mount bone staining, which allows the rapid preparation of highly cleared and nondestructive specimens. It only takes 3 days to complete whole procedure for small vertebrates, such as medaka, zebrafish, and Xenopus frogs. In this procedure, we used a newly developed fixative containing formalin, Triton X-100, and potassium hydroxide, which allows the fixation, decolorization, and transparentization of specimens at the same time. A bone staining solution containing alizarin red S with ethylene glycol and a clearing solution containing Tween 20 and potassium hydroxide also contributed the specificity and swiftness of this new system. As expected, although details of the skeletal system could be observed in specimens with high transparency, it was noteworthy that high-resolution fluorescence images acquired using zoom microscopes clearly delineated the shape of each bone. This new procedure would be expected to be widely used as a standard procedure for bone staining in the testing the developmental toxicity of chemicals and in the screening test of knockout or mutant animals.

Physicochemical systems are strongly modified by spatial confinement; the effect is more pronounced the stronger the confinement is, making its influence particularly important nanotechnology applications. For example, a critical point of a phase transition is shifted by a finite size effect; structure can be changed through wetting to a container wall. Recently, it has been shown that pattern formation during a phase separation is changed when a system is heterogeneously quenched instead of homogeneously. Flux becomes anisotropic due to a heterogeneous temperature field; this suggests that the mechanism behind heterogeneous quenching is different from that of homogeneous quenching. Here, we numerically study the confinement effect for heterogeneously quenched systems. We find that the pattern formed by the phase separation undergoes a topological change with stronger confinement i.e. when the height of a simulation box is varied, transforming from a one-dimensional layered pattern to a two-dimensional pattern. We show that the transition is induced by suppression of the heterogeneous flux by spatial confinement. Systems with heterogeneous flux are ubiquitous; the effect is expected to be relevant to a wide variety of non-equilibrium processes under the action of spatial confinement.

Previous studies have shown that some inflammatory cytokines promote the expression of corticotropin-releasing hormone (CRH) in trophoblasts during pregnancy and that placental CRH could induce the production of adrenocorticotropic hormone (ACTH) in humans. However, whether the same is true in rodent placenta remains unclear. In this study, we examined the effect of pro-inflammatory cytokine LIF on the induction of CRH in mouse trophoblast stem cells (mTSCs). During differentiation, the CRH levels in mTSCs gradually increased. On days 3 and 5 after LIF supplementation, Crh expression in the differentiated mTSCs was significantly increased with LIF treatment than those without LIF treatment. Moreover, the CRH concentration in the culture media increased. Thereafter, we examined the contribution of the downstream pathways of LIF to CRH induction in differentiated mTSCs. The LIF-induced upregulation of CRH was attenuated by inhibition of PI3K/AKT and MAPK phosphorylation but not by inhibition of JAK/STAT3. Therefore, in mTSCs, LIF increased Crh expression through activation of the PI3K/AKT and MAPK pathways but not by the JAK/STAT3 pathway. The present study suggests that mTSC is an ideal in vitro model for studying regulation and function of placental CRH.

Why a catheter can be correctly placed in the ventricle by inserting perpendicular to the frontal bone on the ventricular drainage? We performed a study on the accuracy of a path perpendicular to the skull surface into the anterior horn using computed tomography (CT), and a clinical study. Twenty patients were studied on CT images. Using the curved multi-planar reconstruction method, the curved frontal skull and brain were reconstructed to flat structures, and perpendicular lines were drawn from the flat surface to the foramen of Monro on the reconstructed images. In clinical practice, we made a device which guided a catheter inserting perpendicular to the frontal skull surface, and used it in the ventricular drainage surgery for 148 hydrocephalic patients (158 surgeries). We discovered that the curved surface of the frontal bone around Kocher’s point represents the surface of a globe (mean radius, 75.9 ± 4.3 mm) centering on the foramen of Monro. The distribution of points ranged from 13.5–43.5 mm (mean, 43.5 ± 6.1 mm) to the midline, with points appearing more laterally as ventricular size increased. A catheter was placed in the ventricle in 148 surgeries (99.4%), and the catheter reached the ventricle with correct orientation toward the foramen of Monro in 128 (81.0%). The reason why the ventricular insertion perpendicular to the frontal bone surface can provide a consistent path toward the foramen of Monro is that the curved surface of the frontal bone around Kocher’s point represents the surface of a globe centered on the foramen of Monro.

Here we propose a new protocol for whole-mount bone staining, which allows the rapid preparation of highly cleared and nondestructive specimens. It only takes 3 days to complete whole procedure for small vertebrates, such as medaka, zebrafish, and Xenopus frogs. In this procedure, we used a newly developed fixative containing formalin, Triton X-100, and potassium hydroxide, which allows the fixation, decolorization, and transparentization of specimens at the same time. A bone staining solution containing alizarin red S with ethylene glycol and a clearing solution containing Tween 20 and potassium hydroxide also contributed the specificity and swiftness of this new system. As expected, although details of the skeletal system could be observed in specimens with high transparency, it was noteworthy that high-resolution fluorescence images acquired using zoom microscopes clearly delineated the shape of each bone. This new procedure would be expected to be widely used as a standard procedure for bone staining in the testing the developmental toxicity of chemicals and in the screening test of knockout or mutant animals.

The rapid rise in the prevalence of autism spectrum disorders (ASD) and other psychiatric disorders displaying similar traits has increased the need to elucidate their molecular mechanisms. Epidemiological studies have shown that maternal infection during mid-pregnancy is associated with increased risk of neurodevelopmental disorders such as ASD in offspring. Using maternal infection models, researchers have gathered evidence relevant to such disorders. A comprehensive summary of the changes in the brain structure, function, and behavior in offspring induced by maternal immune activation (MIA) has been reported. However, the molecular mechanisms underlying the association between MIA and improper brain development, which ultimately lead to neurodevelopmental disorders, have not been fully reviewed. This paper summarizes the currently known molecular mechanisms associated with the MIA model, with a special focus on the role of the placenta in fetal brain development.

In a dye-sublimation printer, a thermal print head presses and heats a dye-based ribbon to diffuse ink dyes to the desired positions into the receiving layer of paper. The print quality will deteriorate if the contact condition between the thermal print head and the paper is insufficient. Thus, it is necessary to analyze the contact condition for finer printing. Direct observation of the contact area with an optical microscope is effective to clarify the contact conditions of the thermal print head. However, conventional optical microscopes take too much time to observe the whole apparent contact area, because their fields of view are not sufficiently wide. Previously, we developed a laser microscope with a wide field of view and applied this laser microscope to observe the whole apparent contact area of rubber elements. In this study, we examined the contact conditions between the thermal print head and the paper. In general, when we observe the contact area of two solid surfaces, one is restricted to a transparent material such as a glass plate. Instead of the thermal print head, a glass head of the same shape as an existing thermal print head was pressed on the paper and observed through the glass head. This allowed us to clearly determine the contact situations of the interface and measure the contact widths and distributions of real contact area. In this method, it was confirmed that the contact width and the real contact area changed in accordance with the type of paper used, steps of the printing process, and density of color printing.

It is well known that a droplet pattern is formed during phase separation when the composition of a binary system is asymmetric. Recently, it was reported that concentric and dendritic patterns can...

Analysis of contact conditions between rubber rollers and printing paper is important for stable paper feeding operation. Direct observation of apparent contact area is necessary to understand contact conditions, such as distributions of real contact area and micro-slips. However, conventional optical microscopy takes too long to observe the whole apparent contact area because the field-of-view is too narrow. We developed a wide field-of-view laser microscope, and applied it to determine the distributions of real contact area of rubber rollers against glass plates. Critical torques at which micro-slips of the rubber rollers occurred were proportional to total real contact area.

A 71-year-old man was admitted to our hospital with a diagnosis of subarachnoid hemorrhage (SAH). Angiographies revealed neither aneurysms nor vascular anomalies. However, these images elucidated the occlusion of the left cervical internal carotid artery as well as developed leptomeningeal anastomoses through the ipsilateral posterior cerebral artery, which resulted in blood perfusing the ipsilateral middle and anterior cerebral artery territories. Because the localization of SAH coincided with the developed leptomeningeal anastomosis, we speculated that the rupture of the developed leptomeningeal anastomosis in the basal cistern was the cause of SAH. We performed superficial temporal and middle cerebral artery bypass surgery to prevent rebleeding and ischemic stroke. In patients with occlusion of the internal carotid artery, SAH induced by the rupture of aneurysm formed by hemodynamic stress was recognized. However, rupture of developed leptomeningeal anastomosis should be considered as a possible cause of SAH of unknown origin. (Received March 7, 2016; Accepted August 31, 2016; Published January 1, 2017).