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1.  Gastrojejunostomy for pyloric stenosis after acute gastric dilatation due to overeating 
A 34-year-old woman presented at our hospital with abdominal distention due to overeating. Acute gastric dilatation was diagnosed. The patient was hospitalized, and nasogastric decompression was initiated. On hospitalization day 3, she developed shock, and her respiratory state deteriorated, requiring intubation and mechanical ventilation. Nasogastric decompression contributed to the improvement in her clinical condition. She was discharged 3 mo after admission. During outpatient follow-up, her dietary intake decreased, and her body weight gradually decreased by 14 kg. An upper gastrointestinal series and endoscopy revealed pyloric stenosis; therefore, we performed gastrojejunostomy 18 mo after her initial admission. The patient was discharged from the hospital with no postoperative complications. Gastric necrosis and perforation due to overeating-induced gastric dilatation are life-threatening conditions. Surgical intervention may be required if delayed pyloric stenosis occurs after conservative treatment. We report a case of pyloric stenosis due to overeating-induced gastric dilatation treated by gastrojejunostomy 18 mo after the initial presentation.
PMCID: PMC4316112  PMID: 25663789
Acute gastric dilatation; Bulimia; Pyloric stenosis; Gastrojejunostomy; Gastric necrosis; Gastric perforation
2.  Parvalbumin-expressing interneurons linearly control olfactory bulb output 
Neuron  2013;80(5):10.1016/j.neuron.2013.08.036.
In the olfactory bulb, odor representations by principal mitral cells are modulated by local inhibitory circuits. While dendrodendritic synapses between mitral and granule cells are typically thought to be a major source of this modulation, the contributions of other inhibitory neurons remain unclear. Here we demonstrate the functional properties of olfactory bulb parvalbumin-expressing interneurons (PV cells) and identify their important role in odor coding. Using paired recordings, we find that PV cells form reciprocal connections with the majority of nearby mitral cells, in contrast to the sparse connectivity between mitral and granule cells. In vivo calcium imaging in awake mice reveals that PV cells are broadly tuned to odors. Furthermore, selective PV cell inactivation enhances mitral cell responses in a linear fashion while maintaining mitral cell odor preferences. Thus, dense connections between mitral and PV cells underlie an inhibitory circuit poised to modulate the gain of olfactory bulb output.
PMCID: PMC3884945  PMID: 24239124
3.  Knee Joint Pain Potentially Due to Bone Alterations in a Knee Osteoarthritis Patient 
Patient: Male, 83
Final Diagnosis: Osteoarthritis
Symptoms: Knee joint pain
Medication: —
Clinical Procedure: Resting
Specialty: Orthopedics and Traumatology
Challenging differential diagnosis
Osteoarthritis (OA) is the leading cause of musculoskeletal pain and functional disability worldwide. However, the etiology of this condition is still largely unknown.
Case Report:
We report the clinical course of an elderly man with knee OA.
Plain radiographs and MRI examinations performed during follow-up suggested that the pathophysiology of the patient’s knee OA and joint pain may have been primarily due to bone alterations.
PMCID: PMC4254349  PMID: 25436838
Arthralgia; Knee Joint; Magnetic Resonance Imaging
4.  Mid-Term Results of Computer-Assisted Cervical Pedicle Screw Fixation 
Asian Spine Journal  2014;8(6):759-767.
Study Design
A retrospective study.
The present study aimed to evaluate mid-term results of cervical pedicle screw (CPS) fixation for cervical instability.
Overview of Literature
CPS fixation has widely used in the treatment of cervical spinal instability from various causes; however, there are few reports on mid-term surgical results of CPS fixation.
Record of 19 patients who underwent cervical and/or upper thoracic (C2-T1) pedicle screw fixation for cervical instability was reviewed. The mean observation period was 90.2 months. Evaluated items included Japanese Orthopaedic Association (JOA) score and C2-7 lordotic angle before surgery and at 5 years after surgery. Postoperative computerized tomography was used to determine the accuracy of screw placement. Visual analog scale (VAS) for neck pain and radiological evidence of adjacent segment degeneration (ASD) at the 5-year follow-up were also evaluated.
Mean JOA score was significantly improved from 9.0 points before surgery to 12.8 at 5 years after surgery (p=0.001). The C2-7 lordotic angle of the neutral position improved from 6.4° to 7.8° at 5 years after surgery, but this was not significant. The major perforation rate was 5.0%. There were no clinically significant complications such as vertebral artery injury, spinal cord injury, or nerve root injury caused by any screw perforation. Mean VAS for neck pain was 49.4 at 5 years after surgery. The rate of ASD was 21.1%.
Our mid-term results showed that CPS fixation was useful for treating cervical instability. Severe complications were prevented with the assistance of a computed tomography-based navigation system.
PMCID: PMC4278981  PMID: 25558318
Cervical pedicle screw; Cervical instability; Mid-term results; Adjacent segment degeneration
5.  Comparison of Spinous Process-Splitting Laminectomy versus Conventional Laminectomy for Lumbar Spinal Stenosis 
Asian Spine Journal  2014;8(6):768-776.
Study Design
Seventy-five patients who had been treated for lumbar spinal stenosis (LSS) were reviewed retrospectively.
Invasion into the paravertebral muscle can cause major problems after laminectomy for LSS. To address these problems, we performed spinous process-splitting laminectomy. We present a comparative study of decompression of LSS using 2 approaches.
Overview of Literature
There are no other study has investigated the lumbar spinal instability after spinous process-splitting laminectomy.
This study included 75 patients who underwent laminectomy for the treatment of LSS and who were observed through follow-ups for more than 2 years. Fifty-five patients underwent spinous process-splitting laminectomy (splitting group) and 20 patients underwent conventional laminectomy (conventional group). We evaluated the clinical and radiographic results of each surgical procedure.
Japanese Orthopaedic Association score improved significantly in both groups two years postoperatively. The following values were all significantly lower, as shown with p-values, in the splitting group compared to the conventional group: average operating time (p=0.002), postoperative C-reactive protein level (p=0.006), the mean postoperative number of days until returning to normal body temperature (p=0.047), and the mean change in angulation 2 years postoperatively (p=0.007). The adjacent segment degeneration occurred in 6 patients (10.9%) in the splitting group and 11 patients (55.0%) in the conventional group.
In this study, the spinous process-splitting laminectomy was shown to be less invasive and more stable for patients with LSS, compared to the conventional laminectomy.
PMCID: PMC4278982  PMID: 25558319
Lumbar spinal stenosis; Spinous process-splitting laminectomy; Postoperative low back pain; Paravertebral muscle, posterior approach
6.  Myxopapillary Ependymoma of the Cauda Equina in a 5-Year-Old Boy 
Asian Spine Journal  2014;8(6):846-851.
Myxopapillary ependymoma in childhood typically occurs in the central nervous system. There are few surgical cases of myxopapillary ependymoma of the cauda equina in children. We report a case of myxopapillary ependymoma of the cauda equina in a 5-year-old boy, who presented with leg pain and abnormal gait. Subtotal resection surgery was performed. Following the subtotal tumor resection, follow-up magnetic resonance imaging evaluation showed a recurrent tumor. As a result, we performed a second subtotal tumor resection and followed with postoperative radiation therapy. No further evidence of the disease has been noted elsewhere in the patient in over ten years of follow-up. Myxopapillary ependymoma of the cauda equina in a young boy was improved by subtotal tumor resection and postoperative radiation therapy.
PMCID: PMC4278994  PMID: 25558331
Myxopapillary ependymoma; Child; Radiation therapy; Cauda equina
8.  Intraosseous neurilemmoma of the proximal ulna 
Neurilemmoma is a benign nerve sheath neoplasm commonly located in the soft tissue. Intraosseous neurilemmoma is rare, constituting less than 1% of primary bone tumors.
A 21 year-old woman was presented with left elbow pain of 1-month duration. Plain radiographs showed a well-defined, lytic and expansile lesion of the proximal ulna. Computed tomography revealed cortical destruction and soft tissue extension. Because the tissue of origin for the tumor was uncertain, an open biopsy was performed. The specimens demonstrated a benign spindle cell tumor suggestive of a neurilemmoma, similar to a soft tissue neurilemmoma. The diagnosis of intraosseous neurilemmoma was established. Marginal excision of the soft tissue component and curettage of the lesion in the bone were performed. After 3.5 years of follow up, there is no clinical or radiographic finding to suggest any recurrence.
The major site of intraosseous neurilemmoma is the mandible. Occurrence in the long bone is particularly rare. Only two cases of intraosseous neurilemmoma involving the bones around the elbow have been reported to our knowledge; these cases arose in the distal humerus. We describe the first case of intraosseous neurilemmoma of the proximal ulna of the left elbow. The recommended treatment is conservative resection and bone grafting, as malignant change is extremely rare.
Although very rare, intraosseous neurilemmoma should be taken under consideration in the differential diagnosis of painful, radiographically benign-appearing osseous tumor around the elbow.
PMCID: PMC4275780  PMID: 25460435
Intraosseous neurilemmoma; Elbow; Ulna
9.  Prophylactic and Informational Abdominal Drainage Is Not Necessary After Colectomy and Suprapromontory Anastomosis 
International Surgery  2013;98(4):307-310.
Several randomized prospective studies in western countries regarding the usefulness of prophylactic drainage have concluded that prophylactic abdominal drainage tubes are unnecessary. In Japan, however, longitudinal and vascular margins are rather different from in western countries. Furthermore, body mass index and volume of mesentery differed. Thus, although it is a retrospective study, it is worth investigating the usefulness of prophylactic drainage in the Japanese context. Two hundred sixty patients underwent colectomy and suprapromontory anastomosis. Prophylactic drainage tubes were inserted in 124 cases (47%) and not inserted in 136 cases (53%). In terms of postoperative complications, no statistically significant difference was found between the with-drainage and the without-drainage groups. The incidence of the abscess formation was not statistically different in the with-drainage group (4.0%) or the without-drainage group (0.7%). We concluded that the prophylactic and informational drainage tubes are not necessary even in Japanese cases of suprapromontory anastomosis, which typically have a wide resection and regional lymphadenectomy containing the roots of regional vessels.
PMCID: PMC3829054  PMID: 24229014
Colorectal cancer; Prophylactic drainage; Informational drainage; Suprapromontory anastomosis
10.  Rapid bone destruction in a patient with knee osteoarthritis. A case report and review of the literature 
We report the clinical outcome of an elderly man with knee osteoarthritis (OA) accompanied with recurring severe joint pain. He had no history of trauma to the affected knee. Plain radiographs and magnetic resonance imaging uncovered rapid and severe bone deformity, which likely led to the patient’s progressed radiographic OA. These findings indicate that a pathophysiology of OA may be bone alterations.
PMCID: PMC4269149  PMID: 25568659
knee; osteoarthritis; rapid bone destruction
11.  Motor Branch Biopsy of the Pronator Teres Muscle in a Patient with Painful Forearm Neuropathy 
Case Reports in Neurology  2014;6(2):202-206.
Histological evaluation of a peripheral nerve is often the final diagnostic work-up for a neuropathy of unknown origin, and a distal sensory nerve is usually biopsied. Here, we report the case of a female patient with painful unilateral neuropathy in the upper arm. According to the histological evaluation of the pronator teres motor branch, vasculitis seemed to be the most probable cause of the condition, and steroid therapy improved the patients’ symptoms. A biopsy of the motor branch of the pronator teres muscle nerve may be considered a valuable diagnostic option in selected cases with neuropathy affecting the upper limb, when performed in cooperation with neurologists and orthopedic surgeons.
PMCID: PMC4164103  PMID: 25232332
Motor nerve branch biopsy; Multiple mononeuropathy; Muscle biopsy; Nerve biopsy; Painful neuropathy; Pronator teres
12.  Hepatic Ischemia and Reperfusion Injury in the Absence of Myeloid Cell-Derived COX-2 in Mice 
PLoS ONE  2014;9(5):e96913.
Cyclooxygenase-2 (COX-2) is a mediator of hepatic ischemia and reperfusion injury (IRI). While both global COX-2 deletion and pharmacologic COX-2 inhibition ameliorate liver IRI, the clinical use of COX-2 inhibitors has been linked to increased risks of heart attack and stroke. Therefore, a better understanding of the role of COX-2 in different cell types may lead to improved therapeutic strategies for hepatic IRI. Macrophages of myeloid origin are currently considered to be important sources of the COX-2 in damaged livers. Here, we used a Cox-2flox conditional knockout mouse (COX-2−M/−M) to examine the function of COX-2 expression in myeloid cells during liver IRI. COX-2−M/−M mice and their WT control littermates were subjected to partial liver ischemia followed by reperfusion. COX-2−M/−M macrophages did not express COX-2 upon lipopolysaccharide stimulation and COX-2−M/−M livers showed reduced levels of COX-2 protein post-IRI. Nevertheless, selective deletion of myeloid cell-derived COX-2 failed to ameliorate liver IRI; serum transaminases and histology were comparable in both COX-2−M/−M and WT mice. COX-2−M/−M livers, like WT livers, developed extensive necrosis, vascular congestion, leukocyte infiltration and matrix metalloproteinase-9 (MMP-9) expression post-reperfusion. In addition, myeloid COX-2 deletion led to a transient increase in IL-6 levels after hepatic reperfusion, when compared to controls. Administration of celecoxib, a selective COX-2 inhibitor, resulted in significantly improved liver function and histology in both COX-2−M/−M and WT mice post-reperfusion, providing evidence that COX-2-mediated liver IRI is caused by COX-2 derived from a source(s) other than myeloid cells. In conclusion, these results support the view that myeloid COX-2, including myeloid-macrophage COX-2, is not responsible for the hepatic IRI phenotype.
PMCID: PMC4018446  PMID: 24819536
13.  Surgical treatment of Klippel–Feil syndrome with basilar invagination 
European Spine Journal  2012;22(Suppl 3):380-387.
Klippel–Feil syndrome (KFS) is a congenital cervical vertebral union caused by a failure of segmentation during abnormal development and frequently accompanies conditions such as basicranial malformation, atlas assimilation, or dens malformation. Especially in basilar invagination (BI), which is a dislocation of the dens in an upper direction, compression of the spinomedullary junction from the ventral side results in paralysis, and treatment is required.
Clinical presentation
We present the case of a 38-year-old male patient with KFS and severe BI. Plane radiographs and computed tomography (CT) images showed severe BI, and magnetic resonance image (MRI) revealed spinal cord compression caused by invagination of the dens into the foramen magnum and atlantoaxial subluxation. Reduction by halo vest and skeletal traction were not successful. Occipitocervical fusion along with decompression of the foramen magnum, C1 laminectomy, and reduction using instruments were performed. Paralysis was temporarily aggravated and then gradually improved. Unsupported walking was achieved 24 months after surgery, and activities of daily life could be independently performed at the same time. CT and MRI revealed that dramatic reduction of vertical subluxation and spinal cord decompression were achieved.
Reduction and internal fixation using instrumentation are effective techniques for KFS with BI; however, caution should be exercised because of the possibility of paralysis caused by intraoperative reduction.
PMCID: PMC3641246  PMID: 22926486
Klippel–Feil syndrome; Occipitocervical malformation; Basilar invagination; Surgical treatment
14.  Ewing sarcoma of the thoracic epidural space in a young child 
European Spine Journal  2012;22(Suppl 3):373-379.
To report on the clinical course and treatment of Ewing sarcoma of the thoracic epidural space in a 5-year-old girl.
We present the case of a 5-year-old girl who experienced back pain (day 1); on day 10, the pain had exacerbated and involuntary movements in the lower limbs occurred, and an MRI performed in her local hospital revealed a tumor lesion at the upper thoracic level.
On day 13, emergency surgery was performed for partial resection of the tumor. Pathological examination of the resected tumor by immunostaining and gene testing revealed that it was MIC2 positive and an EWS-FLI 1 chimera, respectively, and Ewing sarcoma was diagnosed. The involuntary movements resolved immediately after the surgery. Three weeks after the operation, chemotherapy and radiation therapy were commenced. After 5 months, deep tendon reflexes recovered to normal. MRI showed that the tumor has not recurred at 29 months after surgery.
The majority of epidural patients undergo emergency surgery only after symptom exacerbation, which includes the development of neurological deficits. Thus, preoperative diagnosis of Ewing sarcoma of the epidural space is difficult and diagnosis is frequently made by a post-operative gene test. The resection area is limited to the intralesional margin area because a larger resection is difficult due to the characteristics of the affected region; thus, there is a higher possibility of recurrence and careful follow-up of the case is necessary.
PMCID: PMC3641242  PMID: 22907727
Ewing sarcoma; Thoracic epidural space; Child
15.  Biological responses according to the shape and size of carbon nanotubes in BEAS-2B and MESO-1 cells 
This study aimed to investigate the influence of the shape and size of multi-walled carbon nanotubes (MWCNTs) and cup-stacked carbon nanotubes (CSCNTs) on biological responses in vitro. Three types of MWCNTs – VGCF®-X, VGCF®-S, and VGCF® (vapor grown carbon fibers; with diameters of 15, 80, and 150 nm, respectively) – and three CSCNTs of different lengths (CS-L, 20–80 μm; CS-S, 0.5–20 μm; and CS-M, of intermediate length) were tested. Human bronchial epithelial (BEAS-2B) and malignant pleural mesothelioma cells were exposed to the CNTs (1–50 μg/mL), and cell viability, permeability, uptake, total reactive oxygen species/superoxide production, and intracellular acidity were measured. CSCNTs were less toxic than MWCNTs in both cell types over a 24-hour exposure period. The cytotoxicity of endocytosed MWCNTs varied according to cell type/size, while that of CSCNTs depended on tube length irrespective of cell type. CNT diameter and length influenced cell aggregation and injury extent. Intracellular acidity increased independently of lysosomal activity along with the number of vacuoles in BEAS-2B cells exposed for 24 hours to either CNT (concentration, 10 μg/mL). However, total reactive oxygen species/superoxide generation did not contribute to cytotoxicity. The results demonstrate that CSCNTs could be suitable for biological applications and that CNT shape and size can have differential effects depending on cell type, which can be exploited in the development of highly specialized, biocompatible CNTs.
PMCID: PMC4000181  PMID: 24790438
multi-walled carbon nanotube; cup-stacked carbon nanotube; cytotoxicity; in vitro; intracellular acidity
16.  Establishment of an Invasive Prostate Cancer Model in Transgenic Rats by Intermittent Testosterone Administration 
We have established a transgenic rat for adenocarcinoma of the prostate (TRAP) model that features uniform adenocarcinoma development in prostatic lobes at high incidence within a short experimental period. However, no invasive carcinomas with reactive stroma characteristics similar to those in man were observed. We therefore have focused on a new model for invasive carcinoma of the prostate using TRAP rats. In experiment 1, male TRAP rats in groups 1 and 2 were treated with orchiectomy at day 0 of the experiment. Rats in groups 1–3 underwent testosterone propionate (TP) implantation from weeks 1 to 4 and from weeks 6 to 16. Rats in groups 1 and 3 were given 3,2’-dimethyl-4-aminobiphenyl (DMAB) after TP implantation. The rats of group 4 served as controls. In experiment 2, the rats were divided into three groups, none of which received DMAB or orchiectomy, treated with TP continuously or with the treatment withdrawn once or twice. In experiment 1, invasive adenocarcinomas with abundant collagenous stroma were found in the dorsolateral and anterior prostate, some of which showed perineural space invasion at week 16. The number of invasive carcinoma foci was most frequent in group 3. In experiment 2, invasive adenocarcinoma development in the lateral prostates was correlated with the number of TP administration/withdrawal cycles. In conclusion, our newly established rat model for invasive adenocarcinoma of the prostate could serve as a useful preclinical model for evaluating the in vivo efficacy of preventive and therapeutic agents targeting of the tumor microenvironment.
PMCID: PMC4000072  PMID: 24791066
prostate cancer; animal model; cancer invasion; transgenic rat; testosterone propionate; intermittent administration
17.  Noncanonical Wnt5a enhances Wnt/β-catenin signaling during osteoblastogenesis 
Scientific Reports  2014;4:4493.
Wnt regulates bone formation through β-catenin-dependent canonical and -independent noncanonical signaling pathways. However, the cooperation that exists between the two signaling pathways during osteoblastogenesis remains to be elucidated. Here, we showed that the lack of Wnt5a in osteoblast-lineage cells impaired Wnt/β-catenin signaling due to the reduced expression of Lrp5 and Lrp6. Pretreatment of ST2 cells, a stromal cell line, with Wnt5a enhanced canonical Wnt ligand-induced Tcf/Lef transcription activity. Short hairpin RNA-mediated knockdown of Wnt5a, but not treatment with Dkk1, an antagonist of Wnt/β-catenin signaling, reduced the expression of Lrp5 and Lrp6 in osteoblast-lineage cells under osteogenic culture conditions. Osteoblast-lineage cells from Wnt5a-deficient mice exhibited reduced Wnt/β-catenin signaling, which impaired osteoblast differentiation and enhanced adipocyte differentiation. Adenovirus-mediated gene transfer of Lrp5 into Wnt5a-deficient osteoblast-lineage cells rescued their phenotypic features. Therefore, Wnt5a-induced noncanonical signaling cooperates with Wnt/β-catenin signaling to achieve proper bone formation.
PMCID: PMC3967152  PMID: 24670389
18.  A Case with Atypical Clinical Course Diagnosed as Osteoarthritis, Osteonecrosis, Subchondral Insufficiency Fracture, or Rapidly Destructive Coxopathy 
Osteonecrosis (ON), subchondral insufficiency fracture (SIF), and rapidly destructive coxopathy (RDC) are considered to be clinically different disorders despite exhibiting several overlapping features. We encountered an elderly female patient with an atypical clinical course who was radiographically diagnosed as having osteoarthritis (OA), ON, SIF, and/or RDC over a long-term follow-up. In this case, radiographic diagnosis was apparently affected by the timing of imaging evaluation and was challenging because of radiographic overlap and atypical disease progression. The disorders of OA, SIF, ON, and RDC might share a similar pathophysiology.
PMCID: PMC4166791  PMID: 25250098
19.  The Pathophysiology and Progression of Hip Osteoarthritis Accompanied with Joint Pain are Potentially Due to Bone Alterations - Follow-up Study of Hip OA Patients 
Objectives :
This study examined hip osteoarthritis (OA) patients with joint pain and accompanying signal changes detected by magnetic resonance imaging (MRI).
Methods :
A total of 19 hip OA patients with suddenly occurring or worsening pain regardless of Kellgren-Lawrence grading were enrolled. The patients were monitored using MRI, plain radiographs, and the Denis pain scale for a minimum of 6 months. The patients were classified into 2 groups: those whose pain improved during conservative treatment (Group A) and those whose pain persisted (Group B).
Results :
Joint pain disappeared or was markedly improved in all 10 cases in Group A. Radiographic OA progression occurred in 7 of 8 cases with available radiographs. Hip MRI was performed on 7 of 10 patients, among whom bone signal changes disappeared in 6 patients. One patient exhibited persisting bone signal alterations although joint pain had completely disappeared. In Group B, joint pain remained in all 9 cases. Radiographic OA progression occurred in 8 of 9 cases, and local (4 cases) or broad (5 cases) bone signal alterations were present in end-point MRI examinations. Two patients exhibited different regional MRI bone signal changes (local or broad) at the end of follow-up. The mean age of Group B was significantly higher than that of Group A.
Conclusion :
This study uncovered the following observations: 1) hip OA with joint pain had bone alterations that were detectable by MRI, 2) these bone alterations disappeared when joint pain improved, 3) bone alterations remained when joint pain continued, and 4) radiographic OA progressed to a more advanced stage over a short time period. These findings indicate that the pathophysiology of OA, joint pain, and OA progression may primarily be due to bone changes.
PMCID: PMC4192849  PMID: 25317214
Bone alteration; hip; joint pain; MRI; OA.
20.  Temporal and Spatial Expression Patterns of Bone Morphogenetic Protein 3 in Developing Zebrafish 
Bone morphogenetic proteins (BMPs) are important elements in bone biology. We herein report the expression profiles of zebrafish bmp3 (zbmp3) as demonstrated by real-time PCR and in situ hybridization. The expression of zbmp3 was highly detectable by real-time PCR from 1 day post-fertilization (1 dpf) to 2 weeks post-fertilization (2 wpf) and peaked at 1 wpf. For in situ hybridization experiments, zbmp3 was expressed in the otic vesicle at 1 dpf, 2 dpf, 3 dpf, and 5 dpf. It was also expressed in the pharyngeal arches, including the opercle, branchiostegal ray, and pectoral fins, at 2 dpf. Our results suggest that zbmp3 may play an important role in the skeletal biology of developing zebrafish.
PMCID: PMC4196250  PMID: 25328556
Bmp3; Expression patterns; Zebrafish.
21.  Dynamic Sensory Representations in the Olfactory Bulb: Modulation by Wakefulness and Experience 
Neuron  2012;76(5):962-975.
How are sensory representations in the brain influenced by the state of an animal? Here we use chronic two-photon calcium imaging to explore how wakefulness and experience shape odor representations in the mouse olfactory bulb. Comparing the awake and anesthetized state, we show that wakefulness greatly enhances the activity of inhibitory granule cells and makes principal mitral cell odor responses more sparse and temporally dynamic. In awake mice, brief repeated odor experience leads to a gradual and long-lasting (months) weakening of mitral cell odor representations. This mitral cell plasticity is odor-specific, recovers gradually over months and can be repeated with different odors. Furthermore, the expression of this experience-dependent plasticity is prevented by anesthesia. Together, our results demonstrate the dynamic nature of mitral cell odor representations in awake animals, which is constantly shaped by recent odor experience.
PMCID: PMC3523713  PMID: 23217744
22.  Overexpression of regenerating gene Iα appears to reflect aberration of crypt cell compartmentalization in sessile serrated adenoma/polyps of the colon 
Diagnostic Pathology  2013;8:187.
Colorectal sessile serrated adenoma/polyps (SSA/Ps) are characterized by asymmetrical distribution of Ki67-positive cells, which varies among crypts and involves the crypt length to a variable extent; the pattern has been designated as aberration of crypt cell compartmentalization. The regenerating gene (REG) Iα is a cell growth and/or anti-apoptotic factor and its overexpression might be associated with aberration of crypt cell compartmentalization in SSA/Ps. We investigated REG Iα expression in SSA/Ps in comparison to hyperplastic polyps (HPs).
A total of 64 cases of serrated polyps (≥10 mm in size), including 53 SSA/Ps and 11 HPs, were included in the present study. Immunostaining was performed using a labeled streptavidin-biotin method. REG Iα expression was classified as follows: (i) expression of endocrine cells: grade 0 (a few positive cells) to 3 (marked increase in positive cells); (ii) expression of goblet cells: grade 0 (negative) to 2 (positive for crypts and surface epithelial cells); (iii) staining intensity of goblet cells: grade 0 (negative) to 2 (strong); (iv) staining intensity of crypt (absorptive) cell membranes: grade 0 (negative) to 2 (strong). The presence of aberration of crypt cell compartmentalization was assessed using Ki67 immunostaining.
With regard to the REG Iα expression of endocrine cells, 8 out of 11 HPs (73%) were grade 0, whereas 51 of 53 SSA/Ps (96%) were grade 1 or higher (p < 0.001). With regard to the distribution of REG Iα-immunoreactive goblet cells, 10 of 11 HPs (91%) were grade 1, whereas 50 of 53 SSA/Ps (94%) were grade 2 (p < 0.001). A similar trend was found in the staining intensity of goblet cells or crypt cell membranes (p = 0.011). Aberration of crypt cell compartmentalization was more frequently identified in SSA/Ps (72%) than in HPs (18%; p = 0.002). A significant association was observed between REG Iα overexpression and the aberration of crypt cell compartmentalization in serrated polyps (p = 0.037).
REG Iα overexpression is a characteristic of SSA/Ps, which appears to reflect aberration of crypt cell compartmentalization.
Virtual slides
The virtual slide(s) for this article can be found here:
PMCID: PMC4225863  PMID: 24225137
Colon; Crypt cell compartmentalization; Hyperplastic polyp; REG Iα; Sessile serrated adenoma/polyp
23.  Sox9 is upstream of microRNA-140 in cartilage 
MicroRNA-140 (miR-140) is Specifically expressed in developing cartilage tissues. We have previously reported that miR-140 plays an important role during palatal cartilage development by modulating platalet-derived growth factor receptor alpha (pdgfra) in zebrafish. However, the regulatory mechanism of miR-140 in cartilage is still unknown. Using developing zebrafish, Sox9a mutant (Sox9a−/−) and Sox9b mutant (Sox9b−/−) zebrafish and Sox9 siRNA in human chondrocytes, T/C-28 Cells, we found that miR-140 is regulated by the cartilage master transcription regulator Sox9 in zebrafish and mammalian cells.
PMCID: PMC3774128  PMID: 22052544
microRNA-140 (miR-140); Sox9; cartilage; zebrafish; T/C-28; SiRNA; in situ hybridization; RT-PCR
24.  Frequency of elevated biomarkers in patients with cryptogenic hepatocellular carcinoma 
The incidence of hepatocellular carcinoma (HCC) continues to increase in Japan, but the clinical characteristics of Japanese patients with HCC have not been well described. The aim of this study was to determine the frequencies and utilities of elevated α-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) levels as biomarkers in cryptogenic HCC.
A total of 2638 patients with HCC diagnosed between 1999 and 2010 in the Nagasaki Association Study of Liver (NASLD) were recruited for this study. The cause of HCC was categorized into 4 groups; HCC-B, HCC-C, HCC-BC, and HCC-nonBC. The significance of factors was examined for HCC-nonBC using logistic regression analysis in all patients.
Multivariate analysis identified age, sex, BMI, alcohol consumption, platelet count, AST, ALT, AFP, DCP, and TNM stage as independent and significant risk factors for HCC-nonBC. According to TNM stage, the median AFP levels in HCC-nonBC with TNM stages I, II, and III were significantly lower than in either HCC-B or HCC-C. In TNM stage IV, the median AFP level in HCC-nonBC was significantly lower than in either HCC-B or HCC-BC. The median DCP levels in HCC-nonBC with TNM stages I and II were significantly higher than those in either HCC-B or HCC-C. In TNM stage III, the median DCP level in HCC-nonBC was significantly higher than that in HCC-C.
DCP was more sensitive than AFP for the diagnosis of early stage cryptogenic HCC. DCP should be used as the main serum test for cryptogenic HCC detection.
PMCID: PMC3775616  PMID: 24008520

Results 1-25 (60)