Prevention of growth arrest-induced cell death of vascular smooth muscle cells by a product of growth arrest-specific gene, gas6

AbstractWe have purified Gas6 as a growth-potentiating factor for vascular smooth muscle cells (VSMCs) [Nakano, T. et al. (1995) J. Biol. Chem. 270, 5702-57051. However, specific production of Gas6 in growth-arrested cells raises an intriguing question as to the physiological function of Gas6. In this study, we found that serum-starved VSMCs secreted some survival factors and depletion of the factors induced cell death of VSMCs. Finally, we demonstrated that cell death was prevented by the addition of Gas6, suggesting that one of the major biological activity of Gas6 is protection of growth-arrested VSMCs from death

Immunohistochemistry of YAP and dNp63 and survival analysis of patients bearing precancerous lesion and oral squamous cell carcinoma

Background: Yes-associated protein (YAP) is a candidate oncogene in various human cancers, and recently, it has been reported that YAP expression and its activity was enhanced by Delta Np63. However, the role of YAP and Delta Np63 expression in carcinogenesis and progression of oral squamous cell carcinoma (OSCC) has been unknown. Therefore, we investigated how YAP and Delta Np63 influence carcinogenesis and progression of OSCC. Methods: We performed immunohistochemical analyses in whole tissue samples to investigate YAP and Delta Np63 expression in normal oral mucosa, epithelial hyperplasia, oral epithelial dysplasia (OED; low/high grade), carcinoma in situ (CIS), and OSCC. Furthermore, in OSCC, we analyzed clinical significance by using Kaplan-Meier survival analysis. Results: In normal oral mucosa and epithelial hyperplasia, YAP expression was primarily confined to the basal and parabasal layers, but YAP expression was elevated in OED, CIS, and OSCC. In OED, YAP and Delta Np63 expression levels were markedly higher in high grade than in low grade. In OSCC groups, YAP and Delta Np63 expression patterns tended to differ according to histopathological differentiation of OSCC. Furthermore, the YAP high expression group, which showed YAP staining in >50% positive cells with strong cytoplasmic staining or >10% positive cells with nuclear reactivity, showed a tendency to have a poor survival rate. Conclusion: YAP and Delta Np63 expression levels correlated with grade of oral OED. Additionally, YAP expression was associated with OSCC survival rate. Our results suggested that YAP and Delta Np63 expression might serve as predictive markers to distinguish OSCC development and progression

“Hook and Roll Technique” Using an Articulating Hook Cautery to Provide a Critical View during Single-incision Laparoscopic Cholecystectomy

We describe a new simple and easy technique called the "Hook and roll technique" (HRT) that uses an articulating hook cautery to provide a critical view during single incision laparoscopic cholecystectomy (SILC). A 2-cm incision is made at the umbilicus to insert three 5-mm trocars or a multichannel port. After dissection of the serosa of the dorsal and ventral sides of the gall bladder, including Calot's triangle, the angled tip of the hook cautery is inserted between the cystic artery and duct with its tip placed dorsally. The tip is then rotated in a clockwise manner to avoid bile duct injury, allowing the connective tissue between them to be hooked, coagulated and cut. This procedure is repeated several times, followed by dissection between the cystic artery and the liver bed to achieve a critical view. From December 2008 to May 2011, 121 patients underwent SILC using HRT in our hospital without any serious complications. This technique is suitable for SILC, as it is consists of simple procedures that can be performed safely and easily, even by left hand in a cross-over approach, and it allows complete dissection of Calot's triangle to achieve a critical view without using any dissector under dangerous in-line viewing

Clinical study on primary screening of oral cancer and precancerous lesions by oral cytology

Background This study was conducted to compare the histological diagnostic accuracy of conventional oral-based cytology and liquid-based cytology (LBC) methods. Methods Histological diagnoses of 251 cases were classified as negative (no malignancy lesion, inflammation, or mild/moderate dysplasia) and positive [severe dysplasia/carcinoma in situ (CIS) and squamous cell carcinoma (SCC)]. Cytological diagnoses were classified as negative for intraepithelial lesion or malignancy (NILM), oral low-grade squamous intraepithelial lesion (OLSIL), oral high-grade squamous intraepithelial lesion (OHSIL), or SCC. Cytological diagnostic results were compared with histology results. Results Of NILM cytology cases, the most frequent case was negative [LBCn = 50 (90.9%), conventionaln = 22 (95.7%)]. Among OLSIL cytodiagnoses, the most common was negative (LBCn = 34; 75.6%, conventionaln = 14; 70.0%). Among OHSIL cytodiagnoses (LBCn = 51, conventionaln = 23), SCC was the most frequent (LBCn = 31; 60.8%, conventionaln = 7; 30.4%). Negative cases were common (LBCn = 13; 25.5%, conventionaln = 14; 60.9%). Among SCC cytodiagnoses SCC was the most common (LBCn = 16; 88.9%, conventionaln = 14; 87.5%). Regarding the diagnostic results of cytology, assuming OHSIL and SCC as cytologically positive, the LBC method/conventional method showed a sensitivity of 79.4%/76.7%, specificity of 85.1%/69.2%, false-positive rate of 14.9%/30.7%, and false-negative rate of 20.6%/23.3%. Conclusions LBC method was superior to conventional cytodiagnosis methods. It was especially superior for OLSIL and OHSIL. Because of the false-positive and false-negative cytodiagnoses, it is necessary to make a comprehensive diagnosis considering the clinical findings

Recovery from heat shock injury by activation of Na+-glucose cotransporter in renal epithelial cells

AbstractExposure of cells or organs to sublethal physical or chemical stresses induces disruption of cellular structures and functions. Here, we examined whether Na+-glucose cotransporter (SGLT1) is involved in the recovery from heat shock (HS) injury in porcine renal epithelial LLC-PK1 cells. Recovery from HS (42 °C for 3 h, then 37 °C for 12 h) increased SGLT1 activity, assessed by [14C]α-methyl glucopyranoside uptake, and a maximal transport rate (Vmax) from 2.4 to 5.9 nmol/mg protein/30 min, but did not alter an apparent affinity constant (Km). Protein distribution of SGLT1 in apical membrane fraction was also increased after recovery from HS without changing in total membrane fraction. Membrane integrity assessed by calcein accumulation was decreased by HS, and then returned to basal level. This recovery was inhibited by phloridzin, a potent SGLT1 inhibitor, and nonmetabolizable glucose analogues. Anti-transforming growth factor-β1 (TGF-β1) antibody inhibited both elevation of SGLT1 distribution in apical membrane and recovery of calcein accumulation induced by HS. Taken together, HS increases in the number of SGLT1 protein in apical membrane mediated via TGF-β1 signaling pathway. The increase of glucose uptake is necessary to repair plasma membrane integrity

Advantage of Alveolar Ridge Augmentation with Bioactive/Bioresorbable Screws Made of Composites of Unsintered Hydroxyapatite and Poly-L-lactide

We studied human bone healing characteristics and the histological osteogenic environment by using devices made of a composite of uncalcined and unsintered hydroxyapatite (u-HA) and poly-L-lactide (PLLA). In eight cases of fixation, we used u-HA/PLLA screws for maxillary alveolar ridge augmentation, for which mandibular cortical bone block was used in preimplantation surgery. Five appropriate samples with screws were evaluated histologically and immunohistochemically for runt-related transcription factor 2 (RUNX2), transcription factor Sp7 (Osterix), and leptin receptor (LepR). In all cases, histological evaluation revealed that bone components had completely surrounded the u-HA/PLLA screws, and the bone was connected directly to the biomaterial. Inflammatory cells did not invade the space between the bone and the u-HA/PLLA screw. Immunohistochemical evaluation revealed that many cells were positive for RUNX2 or Osterix, which are markers for osteoblast and osteoprogenitor cells, in the tissues surrounding u-HA/PLLA. In addition, many bone marrow-derived mesenchymal stem cells were notably positive for both LepR and RUNX2. The u-HA/PLLA material showed excellent bioactive osteoconductivity and a highly biocompatibility with bone directly attached. In addition, our findings suggest that many bone marrow-derived mesenchymal stem cells and mature osteoblast are present in the osteogenic environment created with u-HA/PLLA screws and that this environment is suitable for osteogenesis

Biological Effects of Bioresorbable Materials in Alveolar Ridge Augmentation: Comparison of Early and Slow Resorbing Osteosynthesis Materials

The purpose of this study was to investigate the bone healing properties and histological environment of a u-HA/PLLA/PGA (u-HA-uncalcined and unsintered hydroxyapatite, PLLA-Poly L-lactic acid, PGA-polyglycolic acid) composite device in humans, and to understand the histological dynamics of using this device for maxillofacial treatments. Twenty-one subjects underwent pre-implant maxillary alveolar ridge augmentation with mandibular cortical bone blocks using u-HA/PLLA or u-HA/PLLA/PGA screws for fixation. Six months later, specimens of these screws and their adjacent tissue were retrieved. A histological and immunohistochemical evaluation of these samples was performed using collagen 1a, ALP (alkaline phosphatase), and osteocalcin. We observed that alveolar bone augmentation was successful for all of the subjects. Upon histological evaluation, the u-HA/PLLA screws had merged with the bone components, and the bone was directly connected to the biomaterial. In contrast, direct bone connection was not observed for the u-HA/PLLA/PGA screw. Immunohistological findings showed that in the u-HA/PLLA group, collagen 1a was positive for fibers that penetrated vertically into the bone. Alkaline phosphatase was positive only in the u-HA/PLLA stroma, and the stroma was negative for osteocalcin. In this study, u-HA/PLLA showed a greater bioactive bone conductivity than u-HA/PLLA/PGA and a higher biocompatibility for direct bone attachment. Furthermore, u-HA/PLLA was shown to have the potential for bone formation in the stroma

A Case Report of Primordial Odontogenic Tumor That Required Distinction from a Dentigerous Cyst

Primordial odontogenic tumor (POT) is a rare odontogenic tumor characterized by a variably cellular loose fibrous tissue with areas similar to the dental papilla and covered by cuboidal to columnar epithelium. We herein report a case of POT in a 14-year-old boy. Computed tomography (CT) exhibited a round cavity with a defined cortical border circumscribing the tooth of the second molar. However, the gross finding was a solid mass, not a cyst. Histologically, the tumor consisted of dental papillalike myxoid connective tissue covered by columnar epithelium. Therefore, although the clinical diagnosis was dentigerous cyst (DC), we diagnosed POT based on histologic findings. Clinical findings of POT resemble DC, but the clinical behavior of POT is different to DC, such as cortical expansion and root resorption of teeth. Therefore, histological differentiation of POT from DC is critical for accurate diagnosis

Clinical outcome of tapered wedge stem

The purpose of this study is to evaluate the results and intraoperative or postoperative complications of primary total hip arthroplasty (THA) using a contemporary tapered wedge titanium femoral component. A total of 213 THAs in 187 patients were followed up more than 5 years (mean, 102 months ; range, 60-150). The mean age at surgery was 64.2 years (range, 20–89 years). These patients were clinically evaluated using the JOA scoring system and radiographically host bone reactions around the implants, as well as femoral loosening. The mean JOA score improved from 49 (range, 21–75) to 92 (range, 59–100). All 12 patients with poor results (JOA < 75) coexisted with cerebral, spinal, joint, and musculoskeletal disorders. At the final follow-up, implant survival was 100%. Complications occurred in 23 hips. They consisted of 12 hips with intra-operative fractures, 2 hips with sciatic nerve palsy, one hip with infections, 3 hips with recurrent dislocations, and 8 hips with aseptic cup loosening. In conclusion, we have shown excellent survival rate of the contemporary tapered wedge stem in primary THA ; however, patients with coexisting diseases could not acquire sufficient improvement in hip function and ambulatory ability