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Lamellar corpuscles function as mechanoreceptors in the skin, composed of axon terminals and lamellae constructed by terminal Schwann cells. They are classified into Pacinian, Meissner, and simple corpuscles based on histological criteria. Lamellar corpuscles in rat dermal papilla cells have been reported; however, the morphological aspects have yet to be thoroughly investigated. In the present study, we analyzed the enzyme activity, distribution, fine structure, and three-dimensional innervation of lamellar corpuscles in rat plantar skin. The lamellar corpuscles exhibiting non-specific cholinesterase were densely distributed in rat footpads, evident as notable skin elevations, especially at the apex, the highest portion of the ridges in each footpad. In contrast, only a few lamellar corpuscles were found in other plantar skin areas. Lamellar corpuscle was considered composed of a flat axon terminal Schwann cell lamellae, which were roughly concentrically arranged in the dermal papilla. These histological characteristics correspond to those of the simple corpuscle. Moreover, the axon tracing method revealed that one trunk axon innervated several simple corpuscles. The territory of the trunk axons overlapped with each other. Finally, the animals' footprints were analyzed. During the pausing and walking phases, footpads are often in contact with the floor. These results demonstrate that the type of lamellar corpuscles in the dermal papillae of rat plantar skin is a simple corpuscle and implies that their distribution pattern in the plantar skin is convenient for efficient sensing and transmission of mechanical stimuli from the ground.

Urodele amphibians have exceptional regeneration ability in various organs. Among these, the Iberian ribbed newt (Pleurodeles waltl) has emerged as a useful model organism for investigating the mechanisms underlying regeneration. Neural stem cells (NSCs) are an important source of regeneration in the central nervous system (CNS) and their culture method in vitro has been well established. NSCs form spherical cell aggregates called neurospheres and their formation has been demonstrated in various vertebrates, including some urodele species, but not in P. waltl. In this study, we reported neurosphere formation in brain- and spinal cord-derived cells of post-metamorphic P. waltl. These neurospheres showed proliferative activity and similar expression of marker proteins. However, the surface morphology was found to vary according to their origin, implying that the characteristics of the neurospheres generated from the brain and spinal cord could be similar but not identical. Subsequent in vitro differentiation analysis demonstrated that spinal cord-derived neurospheres gave rise to neurons and glial cells. We also found that cells in neurospheres from P. waltl differentiated to oligodendrocytes, whereas those from axolotls were reported not to differentiate to this cell type under standard culture conditions. Based on our findings, implantation of genetically modified neurospheres together with associated technical advantages in P. waltl could reveal pivotal gene(s) and/or signaling pathway(s) essential for the complete spinal cord regeneration ability in the future.

Glioblastoma multiforme (GBM) is the most prevalent malignant primary brain tumor with a high recurrence rate. Despite multimodal therapy including surgical resection, chemotherapy, and radiotherapy, the median survival time after the initial diagnosis of GBM is approximately 14 months. Since cancer stem cells (CSCs) are considered the leading cause of cancer recurrence, glioblastoma stem cell-targeted therapy is a promising strategy for the treatment of GBM. However, because CSC heterogeneity has been implicated in the difficulties of CSC-target therapy, more in-depth knowledge of CSC biology is still required to develop novel therapies. In this study, we established single cell-derived tumorspheres from human glioblastoma U87MG cells. One of these tumorspheres, P4E8 clone, showed CSC-like phenotypes, such as self-renewal capacity, expression of CSC markers, resistance to anti-cancer agents, and in vivo tumorigenicity. Therefore, we used P4E8 cells as a cell-based model of glioblastoma stem cells (GSCs). Gene expression analysis using microarray indicated that the most highly expressed genes in P4E8 cells compared to the parental U87MG were PC3-secreted microprotein (MSMP). Furthermore, MSMP was expressed in patient-derived GSCs and human glioma tissues at the protein level, implying that MSMP might contribute to glioma development and progression.

Diverse molecular species of sulfatide with differences in FA lengths, unsaturation degrees, and hydroxylation statuses are expressed in the kidneys. However, the physiological functions of specific sulfatide species in the kidneys are unclear. Here, we evaluated the distribution of specific sulfatide species in the kidneys and their physiological functions. Electron microscopic analysis of kidneys of Cst-deficient mice lacking sulfatide showed vacuolar accumulation in the cytoplasm of intercalated cells in the collecting duct, whereas the proximal and distal tubules were unchanged. Immunohistochemical analysis revealed that vacuolar H

Microglia are the primary resident immune cells of the brain parenchyma and transform into the amoeboid form in the "activated state" under pathological conditions from the ramified form in the "resting state" under physiologically healthy conditions. In the present study, we found that microglia in the circumventricular organs (CVOs) of adult mice displayed the amoeboid form with fewer branched cellular processes even under normal conditions; however, those in other brain regions showed the ramified form, which is characterized by well-branched and dendritic cellular processes. Moreover, microglia in the CVOs showed the strong protein expression of the M1 markers CD16/32 and CD86 and M2 markers CD206 and Ym1 without any pathological stimulation. Thus, the present results indicate that microglia in the CVOs of adult mice are morphologically and functionally activated under normal conditions, possibly due to the specialized features of the CVOs, namely, the entry of blood-derived molecules into parenchyma through fenestrated capillaries and the presence of neural stem cells.

Summary Elucidating fine architectures and functions of cellular and synaptic connections requires development of new flexible methods. Here, we created a concept called the “battle of transgenes,” based on which we generated strategies using genetically engineered battles of multiple recombinases. The strategies enabled split-tunable allocation of multiple transgenes. We demonstrated the versatility of these strategies and technologies in inducing strong and multi-sparse allocations of multiple transgenes. Furthermore, the combination of our transgenic strategy and expansion microscopy enabled three-dimensional high-resolution imaging of whole synaptic structures in the hippocampus with simultaneous visualizations of endogenous synaptic proteins. These strategies and technologies based on the battle of genes may accelerate the analysis of whole synaptic and cellular connections in diverse life science fields., Graphical Abstract, Highlights • Generation of BATTLE-recombinase systems for allocation of multiple transgenes • Split-tunable allocation in BATTLE-1 and multi-sparse allocation in BATTLE-2 • Clear and strong labeling of dendrites and axons using BATTLE-2 • 3D high-resolution imaging of whole synapses in hippocampus in BATTLE-1EX, Molecular Biology; Molecular Neuroscience; Neuroanatomy; Techniques in Neuroscience

The sensory circumventricular organs (CVOs) comprise the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO), and area postrema (AP) and lack the blood-brain barrier. The expression of Toll-like receptor 4 (TLR4) was seen at astrocytes throughout the sensory CVOs and at microglia in the AP and solitary nucleus around the central canal. The peripheral and central administration of lipopolysaccharide induced a similar pattern of nuclear translocation of STAT3. A microglia inhibitor minocycline largely suppressed lipopolysaccharide-induced astrocytic nuclear translocation of STAT3 in the OVLT and AP, but its effect was less in the SFO.

Toll-like receptor 4 (TLR4) recognizes bacteria-derived lipopolysaccharide (LPS). In the present study, we found that intraperitoneal LPS activated nuclear factor-κ B (NF-κB) in TLR4-expressing neural stem cells (NSCs) in the circumventricular brain regions of mice. Intracerebroventricular preadministration of low-dose TLR4 inhibitors significantly augmented hyperthermia together with the inhibition of NF-κB activation in circumventricular NSCs of LPS-inflamed animals. Moreover, intracerebroventricular administration of high-dose TLR4 inhibitors induced hyperthermia and Fos activation in circumventricular NSCs and hypothalamic neurons. These results suggest that TLR4 on circumventricular NSCs functions as a central regulator for thermogenesis under inflamed and normal conditions.

We estimated the benefit of a sirolimus-eluting stent (SES, Cypher) for diffuse (> 10 mm) in-stent restenosis (ISR) inside bare metal stents (BMS) because the feasibility of the SES was not confirmed after its recent approval in Japan. Clinical and angiographic outcomes after SES implantation to 93 diffuse ISR were compared with those of 3 groups treated by plain old balloon angioplasty (POBA, (n = 54)), cutting balloon angioplasty (CB, (n = 24)), and BMS (n = 41) in a series of 153 patients whose follow-up quantitative coronary angiography (QCA) evaluated 3-9 months after the treatments was obtained from January 2003 through December 2005. For 33 lesions in the SES group, 12-month follow-up QCA results were obtained and compared with those at 6 months. Ticlopidine (200 mg/day) was prescribed for at least 12 weeks after SES implantation and for 2 weeks after BMS in addition to aspirin (81-100 mg/day). Patient characteristics and the characteristics of previous implanted BMS in the SES group were not significantly different from those in the other groups. Death from cardiac causes and nonfatal myocardial infarction did not occur in any group. Stent thrombosis was not observed in the BMS and SES groups. The incidence of repeat target lesion revascularization (re-TLR) in the SES group (3.23%) was significantly lower compared with that of the POBA (37.0%), CB (25.0%), and BMS (29.3%) groups (P < 0.001, respectively). Late loss in the SES group (0.44 +/- 0.41 mm) was significantly smaller than that in the BMS group (1.34 +/- 0.74 mm) (P < 0.05). The rate of recurrent ISR (re-ISR) in SES (5.38%) was significantly lower than that in POBA (46.3%), CB (41.7%), and BMS (46.3%) (P < 0.001, respectively). The QCA variables at 6 months in the SES group were not significantly different from those at 12 months. Thus, SES implantation for diffuse ISR was far superior since it markedly reduced the incidence of re-TLR with re-ISR at up to 6-months follow-up. In addition, this angiographic patency after SES implantation continued until 12 months.

vic-Difluoro compounds can be directly prepared from epoxides by reaction with Et3N–3HF and DFMBA under microwave-irradiation conditions.

While conventional line generators consisting of rotationally symmetric glass lenses have been widely used for many applications, their optical performances can be improved by using sophisticated optics. Here we report the advantages of our line generators and production technique. We utilize free-form glass lenses to focus laser beams on entire regions of arbitrary-curved surfaces. High energy efficiency is achieved by reducing the size of tool marks left on the lens surfaces. An advanced manufacturing process for free-form surface on carbide materials is briefly discussed.

A case of peritoneal malignant mesothelioma is reported, with some discussion based on the Japanese literature. A 65-year-old man was admitted to the hospital because of abdominal distention in April 1990. As the patient had ascites and node in the Douglas' pouch, a tentative diganosis of peritoneal dissemination from unknown origin was made and exploratory laparotomy was performed. On laparotomy it was found that the greater omentum was replaced with tumor mass and the peritoneum was extensively scattered with numerous nodi 1cm in diameter. Histopathologically, cubic tumor cells lacking the atypia showed a ductal structure, were PAS-positive, and were able to be digested by hyaluronidase. Accordingly, the diagnosis of epithelial type of mesothelioma was confirmed. One week after laparotomy, continuous hyperthermic peritoneal perfusion using CDDP and Mitomycin C was started. Decrease of the ascitic fluid and the degeneration of tumor cells were observed. Until the end of 1990, 240 cases of peritoneal mesothelioma have been reported in Japan. Their average age was 54 years. The male-to-female ratio was 4:3. The diagnosis is difficult without laparotomy or laparoscopy. CDDPbased intraperitoneal chemotherapy seems to be the best available treatment at present. Nevertheless, peritoneal mesothelioma has still poor prognosis.

S状結腸ポリープの一部に未分化癌が発生し, すでに広範囲な肝転移を有していた1例を経験した.症例は60歳, 男性. 注腸造影X線検査, 大腸内視鏡検査でS状結腸に山田IV型のポリープを認めた. 内視鏡的ポリペクトミーを予定していたが, 肝転移を発見したため開腹手術に変更した. 切除したS状結腸ポリープは有茎性で大きさ10×8mm, 組織学的には大部分はvillo-tubular adenomaであったが, ごく一部に未分化癌が発生し, 粘膜下層に浸潤していた. またリンパ節転移と肝転移がみられた. 患者は術後5か月目に死亡した.大腸未分化癌はきわめてまれで, 本邦では5例目の報告である. 自験例のような腺腫内に発生した微小な未分化癌でも悪性度はきわめて高く予後不良である.

A 75-year-old postmenopausal woman with virilization, as demonstrated by temporal baldness, hirsuism, and mustache is presented.Laboratory data on admission revealed polycythemia, markedly elevated plasma testosterone level (29 ng/ml), and normal 17-KS value. Abdominal echography and CT-scan revealed a solid mass of the left ovary. The presumptive diagnosis was a virilizing ovarian tumor. The patient underwent bilateral salpingo-oophorectomy. The resected left ovary measured 3×3×2 cm, and weighted 13 grams.Microscopically, both ovaries were composed of hilar cells. Postoperatively, the plasma testosterone level was recovered to the normal level. The patient has remained asymptomatic.Hilus cell tumors of the ovary are very rare. In Japan, only 4 cases have been reported on the litrature, and besides, bilateral hilus cell tumors are so rare that the case is the 3rd in the world.

The incidence of subacute stent thrombosis (SAT) within 30 days after stenting with a sirolimus-eluting stent (Cypher) for acute myocardial infarction (AMI) was retrospectively compared to that with bare-metal stents (BMS).Among 559 lesions in 558 consecutive AMI from April 2003 to February 2006, the incidence of documented SAT after Cypher implantation (2/276 lesions, 0.72%) was almost the same as for BMS (2 cases, 0.71%). Aspirin (81-100 mg/day) plus ticlopidine (200 mg/day) were administered continuously after admission in all 4 cases.Documented SAT did not increase after stenting with Cypher for AMI under aspirin plus ticlopidine.

Background The incidence of subacute stent thrombosis (SAT) within 30 days after stenting with a sirolimus-eluting stent (Cypher®) for acute myocardial infarction (AMI) was retrospectively compared to that with bare-metal stents (BMS). Methods and Results Among 559 lesions in 558 consecutive AMI from April 2003 to February 2006, the incidence of documented SAT after Cypher® implantation (2/276 lesions, 0.72%) was almost the same as for BMS (2 cases, 0.71%). Aspirin (81-100 mg/day) plus ticlopidine (200 mg/day) were administered continuously after admission in all 4 cases. Conclusion Documented SAT did not increase after stenting with Cypher ® for AMI under aspirin plus ticlopidine. (Circ J 2006; 70: 1091 - 1092)