Platelet-derived Growth Factor Activates Pericytes in the Microvessels of Chronic Subdural Hematoma Outer Membranes.

Angiogenesis is one of the growth mechanisms of chronic subdural hematoma (CSDH). Pericytes have been implicated in the capillary sprouting during angiogenesis and are involved in brain ischemia and diabetic retinopathy. This study examined the pericyte expressions in CSDH outer membranes obtained during trepanation surgery. Eight samples of CSDH outer membranes and 35 samples of CSDH fluid were included. NG2, N-cadherin, VE-cadherin, Tie-2, endothelial nitric oxide synthase (eNOS), platelet-derived growth factor (PDGF) receptor-ß (PDGFR-ß), a well-known marker of pericytes, phosphorylated PDGFR-ß at Tyr751, and ß-actin expressions, were examined using western blot analysis. PDGFR-ß, N-cadherin, and Tie-2 expression levels were also examined using immunohistochemistry. The concentrations of PDGF-BB in CSDH fluid samples were measured using enzyme-linked immunosorbent assay kits. NG2, N-cadherin, VE-cadherin, Tie-2, eNOS, PDGFR-ß, and eNOS expressions in CSDH outer membranes were confirmed in all cases. Furthermore, phosphorylated PDGFR-ß at Tyr751 was also detected. In addition, PDGFR-ß, N-cadherin, and Tie-2 expressions were localized to the endothelial cells of the vessels within CSDH outer membranes by immunohistochemistry. The concentration of PDGF-BB in CSDH fluids was significantly higher than that in cerebrospinal fluid. These findings indicate that PDGF activates pericytes in the microvessels of CSDH outer membranes and suggest that pericytes are crucial in CSDH angiogenesis through the PDGF/PDGFR-ß signaling pathway.

Angiogenesis in the Outer Membrane of Chronic Subdural Hematomas through Thrombin-Cleaved Osteopontin and the Integrin α9 and Integrin ß1 Signaling Pathways.

BACKGROUND: A chronic subdural hematoma (CSDH) is considered to be an inflammatory and angiogenic disease. The CSDH outer membrane, which contains inflammatory cells, plays an important role in CSDH development. Osteopontin (OPN) is an extracellular matrix protein that is cleaved by thrombin, generating the N-terminal half of OPN, which is prominently involved in integrin signal transduction. We explored the expression of the N-terminal half of OPN in CSDH fluid and the expression of integrins α9 and ß1 and the downstream components of the angiogenic signaling pathways in the outer membrane of CSDHs. METHODS: Twenty samples of CSDH fluid and eight samples of CSDH outer membrane were collected from patients suffering from CSDHs. The concentrations of the N-terminal half of OPN in CSDH fluid samples were measured using ELISA kits. The expression levels of integrins α9 and ß1, vinculin, talin-1, focal adhesion kinase (FAK), paxillin, α-actin, Src and ß-actin were examined by Western blot analysis. The expression levels of integrins α9 and ß1, FAK and paxillin were also examined by immunohistochemistry. We investigated whether CSDH fluid could activate FAK in cultured endothelial cells in vitro. RESULTS: The concentration of the N-terminal half of OPN in CSDH fluid was significantly higher than that in the serum. Western blot analysis confirmed the presence of these molecules. In addition, integrins α9 and ß1, FAK and paxillin were localized in the endothelial cells of vessels within the CSDH outer membrane. FAK was significantly phosphorylated immediately after treatment with CSDH fluid. CONCLUSION: Our data suggest that the N-terminal half of OPN in CSDH fluid promotes neovascularization in endothelial cells through integrins α9 and ß1. The N-terminal half of OPN, which is part of the extracellular matrix, plays a critical role in the promotion of CSDHs.

Three-dimensional anatomical structure formed by granule cell layer and pyramidal cell layer in human hippocampus.

In the human hippocampus, the pyramidal layer consists of the inferior aspect of the hippocampus which is organized segmentally. Each segment, together with granule layer of the dentate gyrus, exhibits structural unity. In humans, ellipsoidal protrusions called pyramidal hillocks (PHs), which consist of a thick pyramidal cell layer (PL), are present in the inferior aspect of the hippocampus, and are segmentally organized along a longitudinal axis. It is also known that the granule cell layer (GL) of the dentate gyrus (DG) is not a smooth but undulated structure. However, the cytoarchitectural relationships between the protrusions and undulation have yet to be studied well. Here, we aimed to clarify the three-dimensional cytoarchitecture of the PL and GL of human hippocampus. For that purpose, the GL and PL were three-dimensionally reconstructed from serial sections of human hippocampus stained with hematoxylin and eosin. The GL was shaped as tubing with an opening in the dorsal part, and undulated especially in the medial part, forming digit-like processes. In the base of a digit-like process, protrusions of the GL extended laterally, with longer ones reaching the lateral edge, whereas shorter ones disappeared around the medial 1/3 of the GL. Consequently, the lateral part of the GL was undulated loosely. In the ventral view of the PL, the ellipsoidal PHs were sagittally aligned, whereas in the top view, each PH formed an ellipsoidal trough. Each structural unit was formed by a trough of the PH along the bottom, and had a longer GL protrusion in the upper-center, and shorter GL protrusions located between the longer protrusions and the lateral edge of the GL. A digit-like process extended into a dens. It is concluded that a unit of the PH and the GL comprises the longitudinal segmental formation of the hippocampus.

Topographical relationship between the accessory hepatic duct and the hepatic artery system.

Hepatic biliary injury is one of the most common complications in cholecystectomy and is frequently accompanied by arterial injuries. Because there are several anatomical variations of the hepatic ducts, including the accessory hepatic ducts (AHDs), it is important to consider not only the anatomical position of the hepatic ducts but also those of the AHDs in cholecystectomy. However, the topographical relationships between the AHDs and the hepatic arteries are still poorly understood. In the present study we show that AHDs were observed in 7 out of 59 (11.9%) of the cadavers. There was a single AHD in the 6 out of the 7 cadavers and double AHDs in one. In these cases, the right AHDs emerged from the anterior medial segment of the liver piercing the parenchyma, while the left AHDs emerged directly from the anterior part of the caudate lobe. The right AHDs ran anterior to the right hepatic artery, while the left AHDs ran posterior to the hepatic arteries. The topographical relationship between the AHD and the hepatic artery system was thus reversed in the cases of the right and the left AHDs.

Prognostic nutritional index and postoperative outcomes in patients with colon cancer after laparoscopic surgery.

PURPOSE: The prognostic nutritional index (PNI) is calculated using the serum albumin and peripheral lymphocyte counts. We sought to assess the correlation between the preoperative PNI and postoperative outcomes in patients with colon cancer treated with laparoscopic surgery. METHODS: We included 896 colon cancer patients who underwent curative laparoscopic colectomy between January 2013 and March 2016. To identify any predictors of the postoperative outcomes, we compared the clinical characteristics and immunonutritional parameters, including the PNI, between patients classified as the Clavien-Dindo grade 2 or higher (n = 99) with those classified as grade 0 or 1 (n = 797). RESULTS: A longer surgical time and a preoperative low PNI (< 49.8) (odds ratio; 1.913, p = 0.002) were independent predictors of postoperative complications according to a multivariate analysis. A preoperative low PNI was significantly associated with an older age, a lower performance status, a lower BMI, higher CEA levels, an advanced T status, lymph node metastasis, a longer operative time, a higher blood loss, a larger tumor size, treatment with a combined resection, a longer time to bowel recovery, a longer postoperative hospital stay, and a poor overall survival. CONCLUSIONS: A preoperative low PNI was found to be significantly associated with the incidence of postoperative complications, an advanced tumor status, and a poor prognosis. Further research is needed to understand how to best clinically utilize this promising parameter.

Correlation between musculoskeletal structure of the hand and primate locomotion: Morphometric and mechanical analysis in prehension using the cross- and triple-ratios.

Biometric ratios of the relative length of the rays in the hand have been analyzed between primate species in the light of their hand function or phylogeny. However, how relative lengths among phalanges are mechanically linked to the grasping function of primates with different locomotor behaviors remains unclear. To clarify this, we calculated cross and triple-ratios, which are related to the torque distribution, and the torque generation mode at different joint angles using the lengths of the phalanges and metacarpal bones in 52 primates belonging to 25 species. The torque exerted on the finger joint and traction force of the flexor tendons necessary for a cylindrical grip and a suspensory hand posture were calculated using the moment arm of flexor tendons measured on magnetic resonance images, and were compared among Hylobates spp., Ateles sp., and Papio hamadryas. Finally, the torques calculated from the model were validated by a mechanical study detecting the force exerted on the phalanx by pulling the digital flexor muscles during suspension in these three species. Canonical discriminant analysis of cross and triple-ratios classified primates almost in accordance with their current classification based on locomotor behavior. The traction force was markedly reduced with flexion of the MCP joint parallel to the torque in brachiating primates; this was notably lower in the terrestrial quadrupedal primates than in the arboreal primates at mild flexion. Our mechanical study supported these features in the torque and traction force generation efficiencies. Our results suggest that suspensory or terrestrial quadrupedal primates have hand structures that can exert more torque at a suspensory posture, or palmigrade and digitigrade locomotion, respectively. Furthermore, our study suggests availability of the cross and triple-ratios as one of the indicators to estimate the hand function from the skeletal structure.

Direct evidence of the relationship between brain metastatic adenocarcinoma and white matter fibers: A fiber dissection and diffusion tensor imaging tractography study.

It is commonly known that brain metastases usually have clear boundaries in magnetic resonance imaging. However, little is known regarding the trajectory of white matter fibers around the tumors, especially using the fiber dissection technique. Here, we focused on the anatomical interaction between white matter fibers and the tumor, using the fiber dissection in a postmortem brain with metastatic tumor and compared the findings with those of diffusion tensor imaging (DTI) tractography. One postmortem human brain hemisphere with metastatic adenocarcinoma in the Broca's area was dissected using fiber dissection following the Klingler's method. In order to compare the in vitro and in vivo results, additional brains from 15 patients with metastatic adenocarcinomas, the volumes of which were comparable to that of the adenocarcinoma in the brain used for fiber dissection, were analyzed using DTI tractographic reconstruction. Morphological findings of white matter bundles running around the tumor were compared between the two techniques. In the fiber dissection technique, the superior longitudinal fascicle, arcuate fascicle, and frontal aslant tract could be dissected, and the white matter bundles were curved and retracted to avoid the tumor. In all the cases analyzed, white matter fibers or streamlines surrounding the tumor avoided the lesion. Using the fiber dissection technique, this is the first direct evidence to elucidate the anatomy of white matter fibers affected by a metastatic brain. This suggests that brain metastatic adenocarcinoma is an intra-axial neoplasm with extra-axial white matter structures.

Combinational Approach of Genetic SHP-1 Suppression and Voluntary Exercise Promotes Corticospinal Tract Sprouting and Motor Recovery Following Brain Injury.

Background. Brain injury often causes severe motor dysfunction, leading to difficulties with living a self-reliant social life. Injured neural circuits must be reconstructed to restore functions, but the adult brain is limited in its ability to restore neuronal connections. The combination of molecular targeting, which enhances neural plasticity, and rehabilitative motor exercise is an important therapeutic approach to promote neuronal rewiring in the spared circuits and motor recovery. Objective. We tested whether genetic reduction of Src homology 2-containing phosphatase-1 (SHP-1), an inhibitor of brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling, has synergistic effects with rehabilitative training to promote reorganization of motor circuits and functional recovery in a mouse model of brain injury. Methods. Rewiring of the corticospinal circuit was examined using neuronal tracers following unilateral cortical injury in control mice and in Shp-1 mutant mice subjected to voluntary exercise. Recovery of motor functions was assessed using motor behavior tests. Results. We found that rehabilitative exercise decreased SHP-1 and increased BDNF and TrkB expression in the contralesional motor cortex after the injury. Genetic reduction of SHP-1 and voluntary exercise significantly increased sprouting of corticospinal tract axons and enhanced motor recovery in the impaired forelimb. Conclusions. Our data demonstrate that combining voluntary exercise and SHP-1 suppression promotes motor recovery and neural circuit reorganization after brain injury.

Laparoscopic-endoscopic cooperative surgery for ileal lipoma: A case report.

This is the first report of laparoscopic-endoscopic cooperative surgery (LECS) for an ileal tumor. A 50-year-old man was admitted to our hospital with a positive fecal occult blood test. Colonoscopy detected a submucosal tumor with intussusception located in the ileum, 10 cm oral from the Bauhin valve. On further examination, he was diagnosed with an ileal lipoma. There were no signs of malignancy. LECS was performed for the ileal tumor. After submucosal elevation by injecting saline solution, a mucosal incision was made circumferentially along the tumor. A full-thickness incision was created endoscopically and laparoscopically on the circumferential mucosal incisional line. The tumor was withdrawn intraluminally by endoscopy. The defect of the ileal wall was closed laparoscopically in an axial direction with linear staplers. Histologically, the tumor was a 25-mm ileal lipoma with negative resection margins and no malignancy.

Three forebrain structures directly inform the auditory midbrain of echolocating bats.

Echolocating bats emit various types of vocalizations for navigation and communication, and need to pay attention to vocal sounds. Projections from forebrain centers to auditory centers are involved in the attention to vocalizations, with the inferior colliculus (IC) being the main target of the projections. Here, using a retrograde tracer, we demonstrate that three forebrain structures, namely, the medial prefrontal cortex (mPFC), amygdala, and auditory cortex (AC), send direct descending projections to the central nucleus of IC. We found that all three structures projected to the bilateral IC. A comparison of the patterns of retrogradely labeled cells across animals suggests that the ipsilateral AC-IC projection is topographically organized, whereas mPFC-IC or amygdala-IC projections did not show clear topographic organization. Together with evidence from previous studies, these results suggest that three descending projections to the IC form loops between the forebrain and IC to make attention to various vocal sounds.

Simultaneous laparoscopic left hemicolectomy and spleen-preserving distal pancreatectomy for descending colon cancer with pancreatic invasion.

Here, we describe laparoscopic colectomy with spleen-preserving distal pancreatectomy for descending colon cancer with pancreatic tail invasion. A 69-year-old man with descending colon cancer staged as clinical state IIIC (cT4b [pancreas] N1M0) underwent definitive laparoscopic surgery that was performed in collaboration with surgeons who specialize in laparoscopic colorectal and hepatobiliary-pancreatic laparoscopy. After the left colon was mobilized, tumor infiltration of the pancreas, but not the splenic vessels, was confirmed, and the spleen was preserved. The procedures were safely completed laparoscopically, without intraoperative and postoperative complications. Laparoscopic multivisceral resection could be a treatment option for similar patients but only when performed by multidisciplinary specialists.

Anatomical variations of the torcular Herophili: macroscopic study and clinical aspects.

The anatomical variations of the confluence of sinuses were examined, focusing on the continuity of the superior sagittal sinus (SSS) and the transverse sinuses (TSs). In the 142 specimens studied, there were 72 symmetric cases (50.7%) and 70 asymmetric cases (49.3%). The symmetric group (no dominant type) was categorized into 34 cases of bifurcation (23.9%) and 38 cases of confluence (26.8%). The asymmetric group was categorized into 54 cases of the right-dominant type (38.0%) and 16 cases of the left-dominant type (11.3%). The right-dominant type was further categorized into 38 partially-communicating (26.8%) and 16 non-communicating types (11.3%). The left-dominant type was categorized into 11 partially-communicating (7.7%) and 5 non-communicating types (3.5%). In summary, the SSS asymmetrically drained into one TS in about half of the cases studied. The right-dominant type was about three to four times as common as the left-dominant type. The draining pattern shown by the asymmetric group could provoke intracranial hypertension due to unilateral jugular vein obstruction. In order to avoid this risk in cases of neck dissection, jugular vein catheterization, or hypercoagulopathy, preoperative evaluations of the dural sinus variations via MR venography, three-dimensional CT, or plain X-ray of the skull are recommended.

The middle rectal artery arising from the lateral sacral artery.

A middle rectal artery arising from the lateral sacral artery (MRAls) in the right pelvis of a 99-year-old male was observed. Although variations of the origin of the middle rectal artery have been reported on many occasions, there are few descriptions of the trajectory in the literature. In our case, the MRAls branched from the lateral sacral artery on the sacral surface close to the third sacral sympathetic ganglion and immediately penetrated the third sacral splanchnic nerve and the parasympathetic pelvic splanchnic nerve from the ventral ramus of the forth sacral nerve. The MRAls entered in the lateral wall of the rectal ampulla without giving off a prostatic branch. Preservation of the pelvic autonomic nerves are crucial in rectal cancer excision to preserve the autonomic functions. The close topography of the MRAls to the origin of the fine autonomic nerves should be noted.

Anatomical variations of the recurrent artery of Heubner: number, origin, and course.

The clinical anatomy of the recurrent artery of Heubner (RAH) was examined, focusing on its number, origin, and course, in a large number of brain specimens. We studied 724 RAH in total from 357 brain specimens (714 hemispheres). In 98.74 % of 714 cases there were one or more RAHs, while it was absent in 1.26 % of cases. There was a single RAH in 96.22 % of cases, double in 2.38 % of cases, and triple in 0.14 % of cases. In this study, three origin types of the RAH were defined. We defined A1 and A2 segment of the anterior cerebral artery (ACA) as the artery from the origin of the ACA to the junction of the anterior communicating artery (AComA) and the artery from the junction of the AComA to the anterior border of the corpus callosum, respectively. In 76.2 % of 724 arteries, the RAH originated from the junction of the A1 and A2 segment of the ACA. In 16.3 %, the RAH originated from the A2 segment of the ACA. In 7.5 %, the RAH originated from the A1 segment of the ACA. The course of the RAH was superior to the A1 segment of the ACA in 30.1 % of 724 arteries, anterior in 62.2 %, and posterior in 7.7 %. It is of great importance for neurosurgeons to understand the detailed anatomical variations of the RAH before operating to prevent operative complications resulting in neurological deficits.

Identification of the optimal method for removing the capsule from the acinus of the rat's mandibular glands when preparing specimens for superficial morphology examination.

The superficial morphology of the acinus of the mandibular gland in rats, which corresponds to the submandibular gland in humans, is very difficult to observe under scanning electron microscope due to a closely adherent capsule. Therefore, we evaluated the most effective protocol for removing this capsule from the acinus using various solutions, at different temperatures and for different durations of soaking. Based on the data for 50 male Wistar rats, the most effective method was soaking in an 8 N hydrochloric acid solution at 60°C for 70 min, in a water bath, followed by soaking in a 0.1-0.2% collagenase solution at 37°C for 330-350 min.

Clinical anatomy of the cephalic vein for safe performance of venipuncture.

BACKGROUND: The aims of this study were to elucidate why the cephalic vein provides a reliable cannulation site from a morphological viewpoint and identify an effective landmark for avoiding injury to the superficial branch of the radial nerve (SBRN), allowing for safe venipuncture of the cephalic vein. FINDINGS: We examined 32 forearms and wrists from 18 cadavers. The cephalic vein was a constant structure containing a branch communicating with a collateral vein of the deep palmar arch via the first dorsal interossei muscle. The metacarpal vein from the medial two digits flowed into the cephalic vein. The venous confluence formed 5.8 ± 1.2 cm proximal to the radial styloid process. The SBRN passed 0.4 ± 0.3 cm volar to the venous confluence. The distance between the venous confluence and subcutaneous emergence of the SBRN was 2.6 ± 1.0 cm. CONCLUSIONS: These observations suggest that the cephalic vein is a constant structure that serves as a drainage vein of the hand and provides a reliable cannulation site in the forearm. The venous confluence may serve as a novel landmark to predict the running course of the SBRN.

[A Case of HER2-Positive Stage IV Advanced Gastric Cancer Treated with Chemotherapy Combined with Trastuzumab].

We report a case of human epidermal growth factor receptor(HER)2 positive stage IV advanced gastric cancer successfully treated with chemotherapy combined with trastuzumab. A 50-year-old man was diagnosed with type 3 gastric cancer complicated by liver and lymph node metastases. Owing to a HER2 immunohistochemistry tumor score of 3+, we initiated capecitabine plus CDDP plus trastuzumab chemotherapy. After 6 chemotherapy courses, computed tomography showed the liver metastasis had disappeared and the paraaortic lymph nodes had shrunk. We continued the capecitabine plus trastuzumab chemotherapy, which resulted in a progression free survival of 31 months. After 38 chemotherapy courses, the primary tumor progressed; therefore, the patient underwent surgery. Chemotherapy combined with trastuzumab can allow for resec- tion of the primary tumor.

Three-dimensional structure of seminiferous tubules in the adult mouse.

Seminiferous tubules develop from sex cords, which are embryonic structures with simple C-shaped arches. Histologically, the epithelium of adult mouse seminiferous tubules has been divided into 12 stages based on the associations of spermatogenic cells in four cycles of spermatogenesis. However, the gross characteristics of the seminiferous tubules themselves, including their number, length, run, and mutual relationships remain largely unknown. In the present study, we analyzed all seminiferous tubules in a single adult mouse testis with high resolution using serial paraffin sections and high-perfomance three-dimensional reconstruction software. There were 11 seminiferous tubules with an average length of 140 mm. Each tubule ran along circular paths within the testis while making convolutions with cranial and caudal hairpin turns. The cranial turns of all tubules were in contact with the tunica albuginea, whereas the caudal turns were not, resulting in funnel-shaped networks of these tubules with tapered caudal portions. The caudally located networks surrounded the preceding cranially located networks from the bottom and outside, similar to stacked paper cups. Five out of the 11 seminiferous tubules were continuous from one end to the other both connected with the rete testis (10 connection points). Nine branching points, one blind end, and 18 more connection points with the rete testis were detected in the remaining six seminiferous tubules, making the paths of these tubules complicated to various degrees. The present study revealed that the 3D structures of seminiferous tubules were highly regular as a whole in the adult mouse testis.

Attempt of correlative observation of morphological synaptic connectivity by combining confocal laser-scanning microscope and FIB-SEM for immunohistochemical staining technique.

Ten years have passed since a serial block-face scanning electron microscopy (SBF-SEM) method was developed [1]. In this innovative method, samples were automatically sectioned with an ultramicrotome placed inside a scanning electron microscope column, and the block surfaces were imaged one after another by SEM to capture back-scattered electrons. The contrast-inverted images obtained by the SBF-SEM were very similar to those acquired using conventional TEM. SFB-SEM has made easy to acquire image stacks of the transmission electron microscopy (TEM) in the mesoscale, which is taken with the confocal laser-scanning microcopy(CF-LSM).Furthermore, serial-section SEM has been combined with the focused ion beam (FIB) milling method [2]. FIB-incorporated SEM (FIB-SEM) has enabled the acquisition of three-dimensional images with a higher z-axis resolution com- pared to ultramicrotome-equipped SEM.We tried immunocytochemistry for FIB-SEM and correlated this immunoreactivity with that in CF-LSM. Dendrites of neurons in the rat neostriatum were visualized using a recombinant viral vector. Moreover, the thalamostriatal afferent terminals were immunolabeled with Cy5 fluorescence for vesicular glutamate transporter 2 (VGluT2). After detection of the sites of terminals apposed to the dendrites by using CF-LSM, GFP and VGluT2 immunoreactivities were further developed for EM by using immunogold/silver enhancement and immunoperoxidase/diaminobenzidine (DAB) methods, respectively.We showed that conventional immuno-cytochemical staining for TEM was applicable to FIB-SEM. Furthermore, several synaptic contacts, which were thought to exist on the basis of CF-LSM findings, were confirmed with FIB-SEM, revealing the usefulness of the combined method of CF-LSM and FIB-SEM.