Influence of laser power on atom probe tomographic analysis of boron distribution in silicon.

The relationship between the laser power and the three-dimensional distribution of boron (B) in silicon (Si) measured by laser-assisted atom probe tomography (APT) is investigated. The ultraviolet laser employed in this study has a fixed wavelength of 355nm. The measured distributions are almost uniform and homogeneous when using low laser power, while clear B accumulation at the low-index pole of single-crystalline Si and segregation along the grain boundaries in polycrystalline Si are observed when using high laser power (100pJ). These effects are thought to be caused by the surface migration of atoms, which is promoted by high laser power. Therefore, for ensuring a high-fidelity APT measurement of the B distribution in Si, high laser power is not recommended.

Comparison of mouse and human ankles and establishment of mouse ankle osteoarthritis models by surgically-induced instability.

OBJECTIVE: Prevalence of ankle osteoarthritis (OA) is lower than that of knee OA, however, the molecular mechanisms underlying the difference remain unrevealed. In the present study, we developed mouse ankle OA models for use as tools to investigate pathophysiology of ankle OA and molecular characteristics of ankle cartilage. DESIGN: We anatomically and histologically examined ankle and knee joints of C57BL/6 mice, and compared them with human samples. We examined joints of 8-week-old and 25-month-old mice. For experimental models, we developed three different ankle OA models: a medial model, a lateral model, and a bilateral model, by resection of respective structures. OA severity was evaluated 8 weeks after the surgery by safranin O staining, and cartilage degradation in the medial model was sequentially examined. RESULTS: Anatomical and histological features of human and mouse ankle joints were comparable. Additionally, the mouse ankle joint was more resistant to cartilage degeneration with aging than the mouse knee joint. In the medial model, the tibiotalar joint was markedly affected while the subtalar joint was less degenerated. In the lateral model, the subtalar joint was mainly affected while the tibiotalar joint was less altered. In the bilateral model, both joints were markedly degenerated. In the time course of the medial model, TdT-mediated dUTP nick end labeling (TUNEL) staining and Adamts5 expression were enhanced at early and middle stages, while Mmp13 expression was gradually increased during the OA development. CONCLUSION: Since human and mouse ankles are comparable, the present models will contribute to ankle OA pathophysiology and general cartilage research in future.

Galectin-3 enhances epithelial cell adhesion and wound healing in rat cornea.

BACKGROUND/AIMS: To investigate if galectin-3: (1) enhances adhesion of rat corneal epithelial cells onto a collagen IV substrate and (2) promotes wound healing in rat corneal explants. METHODS: Primary cultures of rat corneal epithelial cells were fixed and immunostained with galectin-3 antibody. To test cellular adherence onto plates coated with collagen type IV, isolated corneal epithelial cells from rats were cultured for 24 h with or without recombinant galectin-3. The attached cells were counted after fixing and staining with 0.1% crystal violet. Direct binding of galectin-3 to collagen IV was tested using a biotin label transfer method. To evaluate wound healing, explants with a 3.5-mm diameter wound in the central corneal epithelium from rats were incubated for 16 h with or without recombinant galectin-3. Changes in the size of the wound were measured with a digital microscope after staining with 5% fluorescein sodium. RESULTS: In rat corneal epithelial cells, galectin-3 was stained throughout the cytoplasm, with increasing density adjacent to the plasma membrane. Exogenous galectin-3, but not epidermal growth factor (EGF), significantly promoted adhesion of corneal epithelial cells onto the collagen IV substrate. Galectin-3 directly bound to collagen IV in vitro. Exogenous galectin-3 significantly enhances wound healing in the corneal explants, which was partially inhibited by ß-lactose. CONCLUSION: Galectin-3 promotes adhesion of corneal epithelial cells onto collagen IV and enhances wound healing in corneal explants. Since galectin-3 functions in promoting wound healing by a different mechanism than that used by EGF, exogenous galectin-3 may be a candidate drug for enhancing epithelial cell wound healing in disorders of the cornea.

Immunohistochemical study of the muscularis externa of the esophagus in achalasia patients.

The etiology of achalasia is believed to be the neuropathy associated with chronic inflammation of the nerve plexus, but the cause of plexus inflammation is unknown. The purpose of this study was to evaluate the pathophysiology of achalasia by examining the muscularis externa of the esophagus. We used the muscularis externa of the esophagus of 62 patients with achalasia (median 44 years, male : female 32:30) who underwent surgical treatment (achalasia group) and of 10 patients (median 65.5 years, male : female 9:1) who underwent esophagectomy for thoracic esophageal cancer (control group) to perform immunohistochemical staining with S-100, CD43, c-kit (CD117), n-NOS, vasoactive intestinal polypeptide (VIP), and ubiquitin. The cell counts that were positive for S-100, n-NOS, VIP, and ubiquitin were significantly lower in the achalasia group compared with the control group (P < 0.001, P= 0.001, P < 0.001, and P= 0.001, respectively). There were no statistically significant differences with respect to CD43 and c-kit staining (P= 0.586 and P= 0.209, respectively). In conclusion, the pathophysiology of achalasia is therefore considered to be an impaired production of NO and VIP, which both affect interstitial cell of Cajal and smooth muscles, and this impairment is therefore considered to play a role in the pathophysiology of achalasia.

Outcomes after repair of the intrathoracic stomach: objective follow-up of up to 5 years.

INTRODUCTION: Laparoscopic surgery is a viable treatment option for intrathoracic stomach (ITS); however, doubts have been raised regarding its efficacy. Routine use of mesh has been advocated. The aim of this study is to look at long-term objective and symptomatic outcomes after repair of ITS with selective use of mesh and fundoplication. MATERIALS AND METHODS: A retrospective review of prospectively collected data was performed for patients who underwent surgical treatment of ITS from January 2004 to April 2009. ITS was defined as herniation of greater than 75% of the stomach into the chest on barium swallow. A standardized foregut symptom questionnaire was administered along with contrast study at 1, 3, and 5 years post surgery. RESULTS: Seventy-three patients with intrathoracic stomach were included in the study. Mean age was 70.6±10.4 (44-88) years, and two-thirds were females. There were 7 transthoracic and 66 transabdominal repairs (64 laparoscopic, 1 open, and 1 laparoscopic to open conversion). There was one intraoperative death, due to bleeding. Antireflux surgery was performed in 43 patients (20 Nissen, 18 Toupet, 1 Dor, and 4 Roux-en-Y gastric bypass (RNYGB)). Ten patients had Collis gastroplasty for short esophagus. Mesh was used in ten (13.7%) patients for crus reinforcement. Objective follow-up was available for 88%, 78%, and 92% patients at 1, 3, and 5 years, respectively. There were 5% (3/61), 11% (4/36), and 17% (2/12) radiological failures at these intervals. There was no significant difference in mean symptom and satisfaction scores or use of proton pump inhibitor (PPI) between patients with and without antireflux surgery. Mean satisfaction scores were 9.1, 9.0, and 9.0 at 1, 3, and 5 years, respectively. CONCLUSION: Laparoscopic repair of ITS with selective use of mesh and fundoplication is feasible, safe, and durable, resulting in a high degree of patient satisfaction.

Trehalose inhibits oral dryness by protecting the cell membrane.

This study assessed the clinical efficacy and acceptability of trehalose solution for oral dryness caused by dental treatment. The efficacy of trehalose on oral dryness under drying conditions was assessed by measuring the surface area of the fungiform papillae and the moisture content of the tongue in seven healthy volunteers. Based on the data from this pilot study, a clinical study was performed, in which the efficacy of oral trehalose spray was evaluated on oral dryness in 10 patients undergoing root canal treatment. The effects of trehalose on cell viability were also assessed under drying conditions in vitro. Trehalose suppressed oral dryness and associated pain caused by dental treatment and protected cells from dryness-related damage. These results indicate that pretreatment application of trehalose solution on the oral mucosa is effective in preventing oral dryness caused by dental treatment.

Dopant distributions in n-MOSFET structure observed by atom probe tomography.

The dopant distributions in an n-type metal-oxide-semiconductor field effect transistor (MOSFET) structure were analyzed by atom probe tomography. The dopant distributions of As, P, and B atoms in a MOSFET structure (gate, gate oxide, channel, source/drain extension, and halo) were obtained. P atoms were segregated at the interface between the poly-Si gate and the gate oxide, and on the grain boundaries of the poly-Si gate, which had an elongated grain structure along the gate height direction. The concentration of B atoms was enriched near the edge of the source/drain extension where the As atoms were implanted.

Transcriptional induction of SOX9 by NF-kappaB family member RelA in chondrogenic cells.

OBJECTIVE: Although SOX9 is a key molecule for chondrogenic differentiation, little is known about the upstream signal. The present study attempted to identify transcription factors to induce SOX9 expression and examined the mechanism. METHODS: Sequences of about 1 kb of 5'-end flanking regions were compared between human and mouse SOX9 genes. In vivo localization was examined by immunohistochemistry in the limb cartilage of fetal mice. Promoter activities of the SOX9, SOX6, and type II collagen (COL2A1) genes were determined in human non-chondrogenic HeLa cells and mouse chondrogenic ATDC5 cells transfected with a luciferase-reporter gene containing the promoter fragments. Protein-DNA binding was examined by electrophoretic mobility shift and chromatin immunoprecipitation assays. The chondrogenic differentiation was assessed by endogenous SOX9, SOX6, and COL2A1 mRNA levels, and by Alcian blue staining and alkaline phosphatase activity. RESULTS: Among transcription factors whose binding motifs were identified in the highly-conserved regions between human and mouse SOX9 promoters, a nuclear factor kappa B (NF-kappaB) member RelA strongly activated the promoter activity. RelA and SOX9 were co-localized in the limb cartilage. Deletion, mutagenesis, and tandem-repeat analyses identified the core region responsive to RelA at the NF-kappaB binding motif to be around -250bp of the human SOX9 promoter, and this was confirmed to show specific binding to RelA. RelA induced the chondrogenic differentiation parameters in HeLa and ATDC5 cells. CONCLUSION: We have identified RelA as a transcriptional factor for SOX9 induction and chondrogenic differentiation via binding to an NF-kappaB binding motif in the SOX9 promoter.

Gastrointestinal quality of life in patients after anti reflux surgery.

A subset of patients does not report improvement of symptoms or satisfaction after antireflux surgery. The aim of this study is to assess the effect of pre-existing depression as a factor in patient satisfaction and gastrointestinal quality of life index (GIQLI) outcomes after antireflux surgery. Patients undergoing antireflux surgery who had filled a preoperative quality of life score and had more than 1 year follow-up were included in this study. Based on available history and self-reported medication use, patients were divided in two groups: with depression (group A) and without depression (group B). Fifty-four patients with completed preoperative GIQLI questionnaire were contacted for this study; 32 (59%) patients completed the postoperative questionnaire. Seven patients (22%) had psychological disorder (group A) in the form of depression The GIQLI in groups A and B increased significantly from 64.4 +/- 17.3 and 89.6 +/- 18.6 to 88.6 +/- 23.7 (P < 0.001) and 102.2 +/- 18.6 (P = 0.02), respectively, after the surgery. There was significant improvement in the quality of life in patients after antireflux surgery based on the GIQLI assessment. This improvement was also reported in patients with history of depression.

Outcomes of surgical treatment of intrathoracic stomach.

The purpose of this study is to assess the long-term outcomes after surgical repair of intrathoracic stomach. Prospectively collected data was retrospectively reviewed. Patients underwent a phone questionnaire 1 year postoperatively to assess gastroesophageal reflux disease-related symptoms and surgical satisfaction. In addition, objective evaluation for integrity of hiatal hernia repair was undertaken either by esophagram or endoscopy. Any recurrence was considered a failure. Forty-one patients underwent surgical repair of a large paraesophageal hernia with intrathoracic stomach during the study period. Thirty-four patients underwent a laparoscopic repair, and seven patients underwent a transthoracic repair. An antireflux procedure was performed on 28 patients, and 13 patients had only hernia reduction and hiatal closure. In the laparoscopic group, two patients required conversion to open laparotomy, as one was unable to tolerate the pneumoperitoneum, and the other had mediastinal bleeding. Thirty-eight (93%) were available for 1-year follow-up. There were three (7.8%) recurrences, one requiring emergency transabdominal repair, and the other two being asymptomatic 1-cm recurrences. All patients report a high degree of satisfaction with surgery. There is a high incidence of short esophagus in patients with intrathoracic stomach. The surgical repair is safe and durable, with high patient satisfaction at 1-year follow-up.

Long-term symptomatic outcomes after Collis gastroplasty with fundoplication.

Collis gastroplasty with fundoplication is an accepted treatment for gastroesophageal reflux disease (GERD) complicated by short esophagus. The procedure can be done either via left thoracotomy or using minimally invasive laparoscopic techniques. Few centers have reported long-term follow-up for patients undergoing a Collis gastroplasty using both the open and minimal access techniques. Retrospective review of prospectively collected data at Creighton University was done to identify patients who underwent Collis gastroplasty with fundoplication for GERD. After approval from the institutional review board, the patients were contacted and administered a questionnaire regarding symptoms and satisfaction. Data were entered in a dataset and analyzed from the patient's perspective. Eighty-five patients underwent a Collis gastroplasty procedure over a period of 13 years. Forty-eight percent (41 cases) were performed laparoscopically, and a transthoracic open repair was performed in the rest. Long-term data (more than 9 months) was available on 52 patients. Surgery resulted in complete resolution of heartburn, chest pain, regurgitation, and dysphagia in 52, 22, 54, and 29% of patients, respectively. More than 75% of the patients were satisfied with the outcome of surgery, and more than 85% would recommend the procedure to another patient. Collis gastroplasty with fundoplication results in good long-term patient satisfaction and symptom control.

Post-operative esophageal leak treated with removable silicone-covered polyester stent.

Self-expanding removable covered stents are increasingly being used for the treatment of benign esophageal diseases such as leaks or perforations and stenosis. They are easy to place and remove and good outcomes have been reported. We report a case of a postoperative esophageal leak successfully managed with a removable silicone-covered polyester stent.

Prediction of recurrence after laparoscopic fundoplication for erosive reflux esophagitis based on anatomy-function-pathology (AFP) classification.

BACKGROUND: The usefulness of the anatomy-function-pathology (AFP) score was examined to evaluate its prediction of recurrence after laparoscopic fundoplication for erosive reflux esophagitis. METHODS: Of the patients undergoing laparoscopic fundoplication for erosive reflux esophagitis of Los Angeles classification grade A or higher from December 1994 to December 2004, 107 who underwent preoperative barium esophagogram, pH monitoring, and endoscopy were selected as subjects. The AFP score was calculated by A, F, and P factor grades of the AFP classification. By comparing patients with and without recurrence, the usefulness of the AFP score for predicting recurrence was examined. RESULTS: Reflux esophagitis recurred in seven patients. No significant difference in age, sex, or A or F factor was observed between the groups, whereas a significant difference was observed in the P factor (p = 0.008). On the other hand, the mean AFP score in the recurrence group was 16.9 +/- 5.3, whereas that in the nonrecurrence group was 8.9 +/- 5.3 (p = 0.0021). Among the patients with a score of 17 points or more (n = 23), recurrence was found in 6 patients (26%). On the other hand, among the patients with a score lower than 17 points (n = 84), recurrence was found in 1 patient, but not in the remaining 83 patients (1%). Sensitivity was thus 85.7% (95% confidence interval [CI], 42.1-99.6), and specificity was 83% (95% CI, 74.2-89.8). The positive predictive value was 26.1% (95% CI, 10.2-48.4), and the negative predictive value was 98.8% (95% CI, 93.5-99.9). Multiple logistic regression analysis was performed, and receiver operating characteristics curves were obtained. The area under the curve for the AFP score was 0.8457, whereas that for the P factor was 0.7907 (p = 0.0045), suggesting that the AFP score may more accurately predict recurrence than the P factor. CONCLUSION: The AFP score may be useful for predicting postoperative recurrence. If surgery is performed when the AFP score is lower than 17 points, the likelihood of postoperative recurrence is expected to be very low.

Laparoscopic Heller myotomy and Dor fundoplication for the treatment of achalasia. Assessment in relation to morphologic type.

BACKGROUND: The significance of laparoscopic Heller myotomy and Dor fundoplication (LHD) for the treatment of achalasia in relation to the severity of the lesion has not been sufficiently assessed. METHODS: Of patients who were diagnosed with achalasia from August 1994 to February 2004, 55 individuals who underwent LHD served as subjects. The therapeutic effects of LHD were assessed in terms of operation time, intraoperative complications, postoperative hospital stay, and symptom improvement in relation to morphologic type (spindle type, Sp; flask type, Fk; and sigmoid type, Sig). Degree of symptomatic improvement was classified into four grades: excellent, good, fair, and poor. RESULTS: Breakdown of morphologic type was as follows: Sp, n = 29; Fk, n = 18; and Sig, n = 8. Excluding one patient for whom conversion to open surgery was required, median average operation time for 54 patients was 160 min. As to intraoperative complications, esophageal mucosal perforation was seen in nine of the 55 patients (16%); however, conversion to open surgery could be avoided by suturing the affected area. Moreover, intraoperative bleeding of at least 100 g was seen in five of the 55 patients (9%), with one Fk patient requiring conversion to open surgery and transfusion. Median postoperative hospital stay was 8 days. Degree of dysphagia relief was excellent in 45 patients (83%), good in eight patients (15%), and fair in one patient (2%). Excellent improvement was obtained in 90%, 88%, and 50% in Sp, Fk, and Sig patients, respectively. Reflux esophagitis was seen in two patients, and was treated with a proton pump inhibitor. CONCLUSIONS: The results of the present study suggest that classification of morphologic type is a useful parameter in predicting postoperative outcome in achalasia. In order to achieve excellent symptomatic relief, surgery for achalasia should be recommended for but not limited to Sp and Fk types.

Time-resolved acquisition technique for elemental mapping by energy-filtering TEM.

A time-resolved acquisition technique for elemental mapping has been investigated for the heavy element barium (Ba) in (Ba(0.5), Sr(0.5)TiO3 (BST) by energy-filtering transmission electron microscopy (EF-TEM). Based on the conventional three-window method, five images were separately acquired for each energy region (about 780 eV signal region, and pre-1 and pre-2 energy regions). After correcting for image shift, the five images were added to form a new processed image in each energy region. Then, Ba element mapping was performed by using the conventional three-window procedure. This time-resolved technique was found to improve signal-to-noise ratio for 100 s total exposure time without increasing the image blurring problem.

Effects of ecabet sodium on experimentally induced reflux esophagitis.

We investigated the effects of ecabet sodium on experimentally induced reflux esophagitis in rats. Three groups of rats, i.e., a control group, esophagitis group, and an ecabet sodium group (25mg/kg given twice daily) were used. The number of animals which developed esophagitis, the extent of the lesions, and the esophagitis lesion index were assessed 3 weeks after the start of the experiment, and the lesions were evaluated histopathologically. All nine surviving rats in the esophagitis group developed esophagitis, and the esophagitis lesion index was 32.6 +/- 7.2 (mean +/- SE) per animal. Histopathologically, thickening of the epithelium, elongation of papillae of the lamina propria into the epithelium, and infiltration of the lamina propria by lymphocytes, eosinophils, plasmacytes, and neutrophils, were observed. Interruption of the lamina of the muscularis mucosae was also observed, and there was marked proliferation of collagen fibers in the submucosa and lamina propria. In the ecabet sodium group, esophagitis developed in five of the nine surviving animals (55.6%), but the esophagitis lesion index was 1.89 +/- 0.73 per animal, which was significantly lower than that in the esophagitis group. The histopathological changes in the rats which developed esophagitis were milder in the ecabet sodium group than in the esophagitis group. These results suggest that ecabet sodium could be useful for the prevention of reflux esophagitis.

Establishment of surgically induced chronic acid reflux esophagitis in rats.

BACKGROUND: The purpose of the study was to establish an animal model of chronic acid reflux esophagitis which could be used for further investigations of the pathophysiology of reflux esophagitis. METHODS: Esophagitis was produced by ligating the transitional region between the forestomach and the glandular portion with a 2-0 silk thread and covering the duodenum near the pylorus ring with a small piece of an 18Fr Nélaton catheter. The histologic features of the esophagus were examined, and the survival rate of these animals was investigated. Moreover, the effects of lansoprazole on this model was studied. RESULTS: The 3-week survival rate was 90%, and esophagitis was noted in all rats. Esophagitis was found 2 or 3 cm above the esophagogastric junction in most cases and at 4.0+/-2.3 sites per animal. Histopathologically, there were increased thickness of the esophageal epithelium, elongation of the lamina propria papillae, which extended upward into the epithelium, marked inflammatory cell infiltration, interruption of the lamina muscularis mucosae, and increase of collagen fibers in the lamina propria and submucosa. These signs were in accord with the histologic features of typical chronic esophagitis. No signs of esophagitis were observed, except in one animal, in the rats given 1 mg/kg/day of lansoprazole. CONCLUSIONS: This experimental rat model is considered useful as a model of chronic acid-type esophagitis for the evaluation of the pathophysiology of reflux esophagitis and the evaluation of drug efficacy.

Formaldehyde treatment suppresses ruminal degradation of phytate in soyabean meal and rapeseed meal.

Most of the P in oilseed meal is in the form of phytate P, and phytate forms complexes with protein. Phytate P has been considered to be absorbed easily in ruminants because of phytate degradation in the rumen. Treatment of oilseed meals with formaldehyde improves the nutritional value of protein through suppressing its ruminal degradation. The present experiment was conducted to study the effects of formaldehyde treatment on phytate degradation in the rumen. The ruminal degradation of phytate in formaldehyde-treated soyabean meal or rapeseed meal was determined by a nylon-bag technique in sheep. Soyabean meal and rapeseed meal were treated with formaldehyde at levels of 3, 5 or 10 g/kg. Treatment with formaldehyde suppressed phytate and protein degradation in both the oilseed meals. Compared with the regular soyabean meal, the regular rapeseed meal showed lower degradability of phytate in the rumen. These results suggest that treatment with formaldehyde suppresses ruminal degradation of phytate in oilseed meal. Thus, the absorption of P from oilseed meal is probably decreased by this treatment in ruminants.

Oncotic pressure regulates gene transcriptions of albumin and apolipoprotein B in cultured rat hepatoma cells.

The mechanism of the accelerated syntheses of albumin and apolipoprotein B (apo B) in response to decreased oncotic pressure was investigated in cultured rat hepatoma H4-II-E cells. Addition of dextran (mol wt 6-9 x 10(4)) to the culture medium decreased the levels of albumin and apo B mRNAs in an oncotic pressure-dependent manner. The reductions of both mRNAs were attenuated with increase in the molecular weight of dextran, which resulted in a decrease in oncotic pressure. Addition of macromolecule increased the viscosity in medium; however, alteration of viscosity appeared not to correlate with albumin and apo B mRNA levels. Transcriptional run-on assays with isolated nuclei from dextran-treated vs. untreated hepatoma cells indicated that the changes in steady-state mRNA levels were mainly controlled at the transcriptional step. Treatment with cycloheximide increased albumin mRNA to the basal level, which was effectively suppressed by dextran, and resulted in superinduction of apo B mRNA. These changes occurred primarily at the transcriptional step. These results suggest that regulations of the expressions of the albumin and apo B genes for adaptive increases in the mRNAs may require the continued synthesis of a labile protein(s) or a limiting transcription factor(s). We conclude that oncotic pressure plays an important role in regulation of expression of the albumin and apo B genes at the transcriptional step.