WorldWideScience

Sample records for femoral intercondylar notch

  1. Femoral intercondylar notch shape and dimensions in ACL-injured patients

    van Eck, Carola F.; Martins, Cesar A. Q.; Vyas, Shail M.; Celentano, Umberto; van Dijk, C. Niek; Fu, Freddie H.

    2010-01-01

    The femoral intercondylar notch has been an anatomic site of interest as it houses the anterior cruciate ligament (ACL). The objective of this study was to arthroscopically evaluate the femoral notch in patients with known ACL injury. This evaluation included establishing a classification for notch

  2. Myositis ossificans within the intercondylar notch treated arthroscopically

    Leung, Allen H.; Desai, Panna; Rybak, Leon D.; Rose, Donald J.

    2010-01-01

    We present a case of intraarticular myositis ossificans in the right knee of a child. Myositis ossificans (MO), though relatively rare in childhood and even more uncommon within a joint, should be included in the differential diagnosis of an intra-articular mass when indicated by the typical clinical, radiographic, and histologic findings. An 11-year-old male presented with a history of trauma to his right knee. Four weeks after the initial injury, an MRI demonstrated evidence of an ACL rupture with a ''cystic mass'' within the intercondylar notch along the anterior surface of the torn ligament. At subsequent arthroscopy, the mass noted on MRI was removed. The histology was consistent with MO. The authors believe this to be the first case of MO in the intercondylar notch detected by MRI, treated by arthroscopy, and confirmed by histology. (orig.)

  3. Myositis ossificans within the intercondylar notch treated arthroscopically

    Leung, Allen H.; Desai, Panna [Hospital for Joint Diseases/New York University, Department of Pathology, New York, NY (United States); Rybak, Leon D. [Hospital for Joint Diseases/New York University, Department of Radiology, New York, NY (United States); Rose, Donald J. [Hospital for Joint Diseases/New York University, Department of Orthopedic Surgery, New York, NY (United States)

    2010-09-15

    We present a case of intraarticular myositis ossificans in the right knee of a child. Myositis ossificans (MO), though relatively rare in childhood and even more uncommon within a joint, should be included in the differential diagnosis of an intra-articular mass when indicated by the typical clinical, radiographic, and histologic findings. An 11-year-old male presented with a history of trauma to his right knee. Four weeks after the initial injury, an MRI demonstrated evidence of an ACL rupture with a ''cystic mass'' within the intercondylar notch along the anterior surface of the torn ligament. At subsequent arthroscopy, the mass noted on MRI was removed. The histology was consistent with MO. The authors believe this to be the first case of MO in the intercondylar notch detected by MRI, treated by arthroscopy, and confirmed by histology. (orig.)

  4. Relationship between mucoid hypertrophy of the anterior cruciate ligament (ACL) and morphologic change of the intercondylar notch: MRI and arthroscopy correlation

    Cha, Ji Hyeon; Shin, Myung Jin; Choi, Byeong Kyoo; Lee, Sang Hoon; Bin, Sung Il

    2008-01-01

    The purpose of this study was to evaluate the relationship between mucoid hypertrophy of the anterior cruciate ligament (ACL) and morphologic change of the intercondylar notch. We retrospectively reviewed the 105 patients with knee magnetic resonance imaging (MRI) with or without knee arthroscopy [group 1: patients with arthroscopic notchplasty (N = 47), group 2: knee arthroscopy demonstrating intact ACL (N = 33), and group 3: patients with normal knee MRI but no arthroscopy (N = 25)]. Groups 2 and 3 served as an arthroscopic and MR control group, respectively. Two musculoskeletal radiologists reviewed all MR examinations. The intercondylar notch width, notch index (width of intercondylar notch/width of femoral condyle), transverse notch angle (TNA), sagittal notch angle (SNA), and notch area were recorded on axial and sagittal MR images at the midpoint of Blumensaat's line which was identified on sagittal images. The diameter of the ACL was recorded on coronal MR images at the posterior end of Blumensaat's line. The mean values of the intercondylar notch width, notch index, TNA, SNA, notch area, and ACL diameter for the three groups were 16.0 mm/0.2/50.3 /36.5 /249.0 mm 2 /7.7 mm (group 1); 19.3 mm/0.3/52.9 /40.2 /323.4 mm 2 /4.8 mm (group 2); and 20.3 mm/0.3/51.4 /39.1 /350.8 mm 2 /4.5 mm (group 3). The intercondylar notch width, notch index, SNA, and notch area were smaller, and ACL diameter was thicker in group 1 compared with the other groups (p < 0.05). Patients with mucoid ACL hypertrophy show a narrower notch, a steeper notch angle, and a smaller notch area than control groups. (orig.)

  5. Incarceration of the medial collateral ligament in the intercondylar notch following proximal avulsion

    Walton, Edward [Fiona Stanley Hospital, Department of Radiology, Perth, Western Australia (Australia); Williams, Martin [North Bristol NHS Trust, Department of Radiology, Bristol (United Kingdom); Robinson, James R. [Bristol Knee Group, Avon Orthopaedic Centre, Bristol (United Kingdom)

    2017-11-15

    Intra-articular entrapment of the medial collateral ligament (MCL) is a rare but recognised complication of traumatic injury to the posteromedial corner (PMC) of the knee. Considering the MCL is the most commonly injured ligament of the knee this complication is extremely rare with only a handful of cases describing MCL entrapment following distal avulsion of the MCL. We present the first known case of MCL entrapment following proximal avulsion of the MCL and posterior oblique ligament (POL) with the mid-substance of the MCL becoming entrapped in the joint, lying on the superior surface of the medial meniscus and extending up into the intercondylar notch. In addition, the medial patellar retinaculum was also entrapped in the medial aspect of the medial patellofemoral joint. MCL entrapment is best treated with expeditious surgical intervention and it is therefore crucial that the MRI findings are not overlooked. Details of the clinical assessment, MRI and operative findings are presented with a literature review of MCL entrapment. (orig.)

  6. Incarceration of the medial collateral ligament in the intercondylar notch following proximal avulsion

    Walton, Edward; Williams, Martin; Robinson, James R.

    2017-01-01

    Intra-articular entrapment of the medial collateral ligament (MCL) is a rare but recognised complication of traumatic injury to the posteromedial corner (PMC) of the knee. Considering the MCL is the most commonly injured ligament of the knee this complication is extremely rare with only a handful of cases describing MCL entrapment following distal avulsion of the MCL. We present the first known case of MCL entrapment following proximal avulsion of the MCL and posterior oblique ligament (POL) with the mid-substance of the MCL becoming entrapped in the joint, lying on the superior surface of the medial meniscus and extending up into the intercondylar notch. In addition, the medial patellar retinaculum was also entrapped in the medial aspect of the medial patellofemoral joint. MCL entrapment is best treated with expeditious surgical intervention and it is therefore crucial that the MRI findings are not overlooked. Details of the clinical assessment, MRI and operative findings are presented with a literature review of MCL entrapment. (orig.)

  7. Radiographic imaging of the canine intercondylar fossa

    Montgomery, R.D.; Fitch, R.B.; Hathcock, J.T.; LaPrade, R.F.; Wilson, M.E.; Garrett, P.D.

    1996-01-01

    The intercondylar fossa is believed to play an important role in the pathology of cranial cruciate ligament rupture and therefore has received considerable attention in the last decade. Accurate radiographic imaging of the intercondylar fossa requires that the central x-ray beam pass through the center of the intercondylar “tunnel”. The anatomy of the canine intercondylar fossa is similar to humans, however, the orientations of the intercondylar fossa's differ. Consequently, the positioning techniques described for humans are not appropriate for the dog. To pass through the center of the dog, intercondylar fossa, the central x-ray beam should be 12° (S.D. 1.7°) caudal from the femoral diaphysis in the sagittal plane and obliqued caudolateral to craniomedial 7° (S.D. 0.60°) (caudo78°proximo7° lateralcraniodistomedial oblique). Cross table positioning was used with the hip flexed and the radiograph cassette placed on the cranial surface of the stifle. However, superimposition of the tuber ischii and soft tissues caudal to the femur made 15° to 20° the best angle obtainable. There was not a significant difference (p = 0.17) in the notch width index between a 12° versus 20° angle of the central x-ray beam caudal to the femoral diaphysis, both with 7° of external rotation of the stifle. The notch width index of 0.252 obtained from radiographic measurements was not significantly different from measurements obtained grossly of 0.254 (n = 26; p = 0.69). Failure to oblique the central x-ray beam caused a significant (p = 0.0008) decrease in the apparent fossa width radiographically

  8. Relationship Between the Risk of Suffering a First-Time Noncontact ACL Injury and Geometry of the Femoral Notch and ACL: A Prospective Cohort Study With a Nested Case-Control Analysis.

    Whitney, Darryl C; Sturnick, Daniel R; Vacek, Pamela M; DeSarno, Mike J; Gardner-Morse, Mack; Tourville, Timothy W; Smith, Helen C; Slauterbeck, James R; Johnson, Robert J; Shultz, Sandra J; Hashemi, Javad; Beynnon, Bruce D

    2014-08-01

    The morphometric characteristics of the anterior cruciate ligament (ACL) and the femoral intercondylar notch within which it resides have been implicated as risk factors for injuries to this important stabilizer of the knee. Prior research has produced equivocal results with differing methodologies, and consequently, it is unclear how these characteristics affect the injury risk in male and female patients. The morphometric characteristics of the ACL and femoral intercondylar notch are individually and independently associated with the risk of suffering a noncontact ACL injury, and these relationships are different in male and female patients. Case-control study; Level of evidence, 3. Magnetic resonance imaging scans of the bilateral knees were obtained on 88 case-control pairs (27 male, 61 female) matched for age, sex, and participation on the same sports team. Patients had suffered a grade III, first-time, noncontact ACL tear. The femoral notch width at 4 locations, the thickness of the bony ridge at the anteromedial outlet of the femoral notch, the femoral notch volume, ACL volume, and ACL cross-sectional area were measured. Multivariate analysis of combined data from male and female patients revealed that decreased ACL volume (odds ratio [OR], 0.829), decreased femoral notch width (OR, 0.700), and increased bony ridge thickness at the anteromedial outlet of the femoral notch (OR, 1.614) were significant independent predictors of an ACL injury. Separate analyses of male and female patients indicated that the femoral notch ridge may be more strongly associated with a risk in female patients, while ACL volume is more strongly associated with a risk in male patients. However, statistical analysis performed with an adjustment for body weight strengthened the association between ACL volume and the risk of injuries in female patients. Morphometric features of both the ACL and femoral notch combine to influence the risk of suffering a noncontact ACL injury. When

  9. Long Term Survivorship of a Severely Notched Femoral Stem after Replacing the Fractured Ceramic head with a Cobalt-Chromium Head.

    Panagopoulos, Andreas; Tatani, Irini; Megas, Panagiotis

    2016-01-01

    Although ceramic head fracture occurs infrequently today, in the event of a fracture, the resulting revision surgery can prove very challenging, since the ceramic particles lodge into the surrounding soft tissue and can cause rapid implant failure. A case of long term survivorship of a severed notched femoral stem after replacing the fractured femoral head with a cobalt-chromium one is reported in a 40-year old woman with hip dysplasia who underwent an uncomplicated total hip arthroplasty. The incident of ceramic femoral head fracture occurred 14 months postoperatively without reporting any significant trauma. Intraoperative findings at revision were a multifragmented femoral head and a damaged polyethylene insert along with diffuse metallosis and excessive wear of the cone of the stem. Both the stem and the acetabular component were stable. After removal of ceramic fragments, metallotic tissue excision and careful lavage of the joint, the inlay was replaced by a similar one and a cobalt-chromium femoral head was placed to the existing notched taper of the firmly incorporated stem. At the 13 th year follow up examination, the patient had no pain, used no walking aids, and had normal activity with no signs of wearing or loosening in the plain x-rays. Despite current recommendations of using ceramic femoral heads in cases of fracture or to revise the severely damaged stems we were able to provide a long term survivorship up to 13 years postoperatively of a cobalt-chromium femoral head applied to a severe damaged stem.

  10. The intercondylar fossa of the normal canine stifle: an anatomic and radiographic study

    Fitch, Randall B.; Montgomery, Ronald D.; Milton, James L.; Garrett, Phillip D.; Kincaid, Steven A.; Wright, James C.; Terry, Glenn C.

    1995-01-01

    The intercondylar fossa (ICF) in dogs consists of a cranial outlet, intercondylar shelf, caudal arch, caudal outlet, a medial wall, and a lateral wall. The normal cranial outlet is bell-shape and, in mixed-breed dogs (mean body weight 19.2 kg, N = 21), measured 5.8 mm cranially, 8.1 mm centrally, and 10.3 mm caudally. The ICF is oriented 12 degree from the dorsal plane of the femoral diaphysis and obliqued 7 degree , proximolateral to distomedial, in the sagittal plane. To adjust for dog size, a fossa width index (FWI) was calculated by dividing the cranial outlet width by the distance between epicondyles. The normal FWI as determined in this study was 0.18 cranially, 0.25 centrally, and 0.32 caudally. The fossa height index was 0.31. Contact between the ICF and the cranial cruciate ligament began at about 115 degree of extension. The contact area moved cranially in the intercondylar fossa as the stifle was extended. Evaluation of the ICF can be performed radiographically but positioning is critical

  11. In Vivo Quantitative Ultrasound Image Analysis of Femoral Subchondral Bone in Knee Osteoarthritis

    Jana Podlipská

    2013-01-01

    Full Text Available A potential of quantitative noninvasive knee ultrasonography (US for detecting changes in femoral subchondral bone related to knee osteoarthritis (OA was investigated. Thirty-nine patients referred to a knee arthroscopy underwent dynamic noninvasive US examination of the knee joint. The subchondral bone was semiautomatically segmented from representative US images of femoral medial and lateral condyles and intercondylar notch area. Subsequently, the normalized mean gray-level intensity profile, starting from the cartilage-bone interface and extending to the subchondral bone depth of ~1.7 mm, was calculated. The obtained profile was divided into 5 depth levels and the mean of each level, as well as the slope of the profile within the first two levels, was calculated. The US quantitative data were compared with the arthroscopic Noyes’ grading and radiographic Kellgren-Lawrence (K-L grading. Qualitatively, an increase in relative subchondral bone US gray-level values was observed as OA progressed. Statistically significant correlations were observed between normalized US mean intensity or intensity slope especially in subchondral bone depth level 2 and K-L grading (r=0.600, P<0.001; r=0.486, P=0.006, resp. or femoral arthroscopic scoring (r=0.332, P=0.039; r=0.335, P=0.037, resp.. This novel quantitative noninvasive US analysis technique is promising for detection of femoral subchondral bone changes in knee OA.

  12. Lateral femoral notch depth is not associated with increased rotatory instability in ACL-injured knees: a quantitative pivot shift analysis.

    Kanakamedala, Ajay C; Burnham, Jeremy M; Pfeiffer, Thomas R; Herbst, Elmar; Kowalczuk, Marcin; Popchak, Adam; Irrgang, James; Fu, Freddie H; Musahl, Volker

    2018-05-01

    A deep lateral femoral notch (LFN) on lateral radiographs is indicative of ACL injury. Prior studies have suggested that a deep LFN may also be a sign of persistent rotatory instability and a concomitant lateral meniscus tear. Therefore, the purpose of this study was to evaluate the relationship between LFN depth and both quantitative measures of rotatory knee instability and the incidence of lateral meniscus tears. It was hypothesized that greater LFN depth would be correlated with increased rotatory instability, quantified by lateral compartment translation and tibial acceleration during a quantitative pivot shift test, and incidence of lateral meniscus tears. ACL-injured patients enrolled in a prospective ACL registry from 2014 to 2016 were analyzed. To limit confounders, patients were only included if they had primary ACL tears, no concurrent ligamentous or bony injuries requiring operative treatment, and no previous knee injuries or surgeries to either knee. Eighty-four patients were included in the final analysis. A standardized quantitative pivot shift test was performed pre-operatively under anesthesia in both knees, and rotatory instability, specifically lateral compartment translation and tibial acceleration, was quantified using tablet image analysis software and accelerometer sensors. Standard lateral radiographs and sagittal magnetic resonance images (MRI) of the injured knee were evaluated for LFN depth. There were no significant correlations between LFN depth on either imaging modality and ipsilateral lateral compartment translation or tibial acceleration during a quantitative pivot shift test or side-to-side differences in these measurements. Patients with lateral meniscus tears were found to have significantly greater LFN depths than those without on conventional radiograph and MRI (1.0 vs. 0.6 mm, p quantitative measures of rotatory instability. Concomitant lateral meniscus injury was associated with significantly greater LFN depth. Based on

  13. Does the lateral intercondylar ridge disappear in ACL deficient patients?

    van Eck, C.F.; Martins, C.A.Q.; Vyas, S.M.; Celentano, U.; van Dijk, C.N.; Fu, F.H.

    2010-01-01

    The aim of this study was to determine whether there is a difference in the presence of the lateral intercondylar ridge and the lateral bifurcate ridge between patients with sub-acute and chronic ACL injuries. We hypothesized that the ridges would be present less often with chronic ACL deficiency.

  14. Adult tibial intercondylar eminence fracture: evaluation with MR imaging

    Toye, Leon R.; Cummings, Dean P.; Armendariz, Gus

    2002-01-01

    Tibial intercondylar eminence (TIE) fractures are well described in the pediatric orthopedic literature. Adult TIEs are much less common, and limited literature exists on the subject. Adult knee hyperextension injuries commonly result in anterior cruciate ligament (ACL) injury; however, with significant trauma, a TIE enters the differential diagnosis. Identification and classification of TIE fractures typically has been provided by radiography. The incidence of concomitant injuries with magnetic resonance (MR) imaging in patients with adult TIE fractures has not been determined. We present a case of an adult type III TIE fracture seen on radiography that only with further MR imaging revealed a concomitant lateral tibial plateau fracture. Utilization of MR imaging altered the surgeon's course of treatment and postoperative care. Radiographic and MR images and a review of the literature are provided. (orig.)

  15. Flexing and downsizing the femoral component is not detrimental to patellofemoral biomechanics in posterior-referencing cruciate-retaining total knee arthroplasty

    Marra, Marco A.; Strzelczak, Marta; Heesterbeek, Petra J.C.; van de Groes, Sebastiaan A.W.; Janssen, Dennis; Koopman, Bart F.J.M.; Verdonschot, Nico; Wymenga, Ate B.

    2018-01-01

    Purpose: When downsizing the femoral component to prevent mediolateral overhang, notching of the anterior femoral cortex may occur, which could be solved by flexing the femoral component. In this study, we investigated the effect of flexion of the femoral component on patellar tendon moment arm,

  16. Radiographic and computed tomographic evaluation of the canine intercondylar fossa in normal stifles and after notchplasty in stable and unstable stifles

    Fitch, R.B.; Hathcock, J.T.; Montgomery, R.D.

    1996-01-01

    The role of the intercondylar fossa in cranial cruciate ligament injury has gained notable attention in humans and it's role is now being questioned in animals. Controversy exists regarding the accuracy of radiographs and computed tomography (CT) in evaluating the intercondylar fossa. This study compared radiographic and CT evaluation with gross evaluation of the intercondylar fossa. Six greyhounds were evaluated before notchplasty, immediately after notchplasty and 6 months after notchplasty in stable and unstable stifles. A fossa width index was used for comparison because it negates the effects of patient size and radiographic magnification. The fossa width index is calculated by dividing the width of the intercondylar fossa by the total condylar width. The fossa width indices of dogs determined from radiographs and CT were not significantly different before notchplasty except for the cranial fossa width indices which were more inconsistent and tended to underestimate the size when compared to gross measurements. At six months, both stable and unstable stifles had refilling of the notchplasty, but the unstable stifles had significantly greater refilling resulting in no significant enlargement in intercondylar fossa size as compared to the prenotchplasty size. Osteophytes that occurred within the intercondylar fossa were less radiopaque and more easily visualized by computed tomography. Computed tomography provided several advantages, including clearer visualization of the intercondylar fossa, avoiding superimposition of the intercondylar fossa by caudal thigh muscles or tuber ischii and the ability to analyze the cranial and caudal components of the intercondylar fossa separately

  17. [Antero-medial incision of knee joint for the treatment of intercondylar fracture of femur].

    Yin, Zi-Fei; Sun, Bin-Feng; Yang, Xiao-Hai; Wang, Qing; Qian, Ping-Kang; Wu, Xiao-Feng; Xu, Feng

    2017-12-25

    To explore the clinical effect of antero-medial incision of knee joint in treating intercondylar fracture of femur. From September 2012 to March 2015, 24 patients with intercondylar fracture of femur were selected, including 17 males and 7 females, aged from 20 to 65 years old with an average of(38.3±9.5) years old. Among them, 12 cases were caused by traffic accident, 8 cases were caused by falling injury and 4 cases were caused by falling down. All patients were closed fractures. The time from injury to hospital was from 30 min to 8 h with an average of(2.2±0.3) h. According to AO classification, 4 cases were type B1, 3 type B2, 2 type B3, 5 type C1, 6 type C2 and 4 type C3. All patients were treated with antero-medial incision of knee joint. Operative time, blood loss and postoperative complications were observed and recovery of keen function was evaluated by Kolmert scoring. All patients were followed-up from 6 to 12 months with average of (9.0±1.7) months. Operative time ranged from 50 to 90 min with an average of (70.0±8.2) min; blood loss ranged from 90 to 400 ml with an average of (180±36) ml; negative pressure flow was from 30 to 90 ml, with an average of (50.0±7.1) ml. All fracture were healed at stage I without loosening of internal fixator, fracture nonunion, and deep vein thrombosis. According to Kolmert scoring, 16 patients got excellent result, 5 patients good and 3 fair. Antero-medial incision of knee joint in treating intercondylar fracture of femur, which has advantages of good fracture reduction, less injury of soft tissue and simple operation, could obtain good clinical results.

  18. Application of 3D-printing technology in the treatment of humeral intercondylar fractures.

    Zheng, W; Su, J; Cai, L; Lou, Y; Wang, J; Guo, X; Tang, J; Chen, H

    2018-02-01

    This study was aimed to compare conventional surgery and surgery assisted by 3D-printing technology in the treatment of humeral intercondylar fractures. In addition, we also investigated the effect of 3D-printing technology on the communication between doctors and patients. A total of 91 patients with humeral intercondylar fracture were enrolled in the study from March 2013 to August 2015. They were divided into two groups: 43 cases of 3D-printing group, 48 cases of conventional group. The individual models were used to simulate the surgical procedures and carry out the surgery according to plan. Operation duration, blood loss volume, fluoroscopy times and time to fracture union were recorded. The final functional outcomes, including the motion of the elbow, MEPS and DASH were also evaluated. Besides, we made a simple questionnaire to verify the effectiveness of the 3D-printed model for both doctors and patients. The operation duration, blood loss volume and fluoroscopy times for 3D-printing group was 76.6±7.9minutes, 231.1±18.1mL and 5.3±1.9 times, and for conventional group was 92.0±10.5minutes, 278.6±23.0mL and 8.7±2.7 times respectively. There was statistically significant difference between the conventional group and 3D-printing group (p3D-printing model. This study suggested the clinical feasibility of 3D-printing technology in treatment of humeral intercondylar fractures. Level II prospective randomized study. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Deep lateral notch sign and double notch sign in complete tears of the anterior cruciate ligament: MR imaging evaluation

    Grimberg, Alexandre [University of California, San Diego School of Medicine, Division of Musculoskeletal Radiology, Department of Radiology, San Diego, CA (United States); Universidade Federal de Sao Paulo, Department of Diagnostic Imaging, Sao Paulo, SP (Brazil); Shirazian, Hoda; Torshizy, Hamid; Smitaman, Edward; Resnick, Donald L. [University of California, San Diego School of Medicine, Division of Musculoskeletal Radiology, Department of Radiology, San Diego, CA (United States); Chang, Eric Y. [Veterans Administrations San Diego Healthcare Systems, Osteoradiology Section, Department of Radiology, San Diego, CA (United States); University of California, San Diego School of Medicine, Division of Musculoskeletal Radiology, Department of Radiology, San Diego, CA (United States)

    2014-11-20

    To systematically compare the notches of the lateral femoral condyle (LFC) in patients with and without complete tears of the anterior cruciate ligament (ACL) in MR studies by (1) evaluating the dimensions of the lateral condylopatellar sulcus; (2) evaluating the presence and appearance of an extra or a double notch and its association with such tears. This retrospective study was approved by our institutional review board, and informed written patient consent was waived. In 58 cases of complete ACL tears and 37 control cases with intact ACL, the number of notches on the LFC was determined, and the depth and anteroposterior (AP) length of each notch were measured in each third of the LFC. The chi-square test, t-test, and logistic regression model were used to analyze demographic data and image findings, as appropriate. Presence of more than one notch demonstrated a sensitivity of 17.2 %, specificity of 100 %, positive predictive value of 100 %, and negative predictive value of 43.5 % for detecting a complete ACL tear. Lateral third depth measurement (p = 0.028) was a significant associated finding with a complete ACL tear. A deep notch in the lateral third of the LFC is a significant associated finding with a complete ACL tear when compared with an ACL-intact control group, and the presence of more than one notch is a specific but insensitive sign of such a tear. (orig.)

  20. Proximal tibial osteophytes and their relationship with the height of the tibial spines of the intercondylar eminence: paleopathological study

    Hayeri, Mohammad Reza; Shiehmorteza, Masoud; Trudell, Debra J.; Resnick, Donald; Hefflin, Tori

    2010-01-01

    Tibial spiking (i.e., spurring of tibial spines), eburnation, and osteophytes are considered features of osteoarthritis. This investigation employed direct inspection of the medial and lateral tibial plateaus in paleopathological specimens to analyze the frequency and morphological features of osteoarthritis and to define any relationship between the size of osteophytes and that of the intercondylar tibial spines. A total of 35 tibial bone specimens were evaluated for the degree of osteoarthritis and presence of eburnation. Each plateau was also divided into four quadrants and the presence and size of bone outgrowths were recorded in each quadrant. The ''medial/lateral tibial intercondylar spine index'' for each specimen was calculated as follows: (medial/lateral intercondylar tibial spine height)/(anteroposterior width of the superior tibial surface). The relationships between medial and lateral tibial height indexes with the degree of osteoarthritis were then tested. Osteophytes were observed more frequently in the anterior quadrants of both tibial plateaus than in the posterior quadrants (29 vs 16 for the medial tibial plateau [p = 0.01] and 28 vs 20 for the lateral tibial plateau [p = 0.04]). Eburnation was seen more frequently in the posterior regions of both tibial plateaus than in the anterior regions (17 vs 5, p < 0.01). In specimens with no signs of osteoarthritis the lateral intercondylar tibial index was significantly lower than that in specimens with some degree of osteoarthritis (p = 0.02). The medial intercondylar tibial index of the specimens with no signs of osteoarthritis was not significantly different from that of the specimens with some degree of osteoarthritis (p = 0.45). There was a positive correlation between the lateral spine height index and the overall grading of osteoarthritis, (r = 0.6, p < 0.01). In the anteromedial and posteromedial quadrants of the lateral tibial plateau, the association between the lateral intercondylar tibial spine

  1. Proximal tibial osteophytes and their relationship with the height of the tibial spines of the intercondylar eminence: paleopathological study

    Hayeri, Mohammad Reza [Children' s National Medical Center, Department of Radiology, Washington, DC (United States); Shiehmorteza, Masoud; Trudell, Debra J.; Resnick, Donald [University of California San Diego, Department of Radiology, San Diego, CA (United States); Hefflin, Tori [Museum of Man San Diego, San Diego, CA (United States)

    2010-09-15

    Tibial spiking (i.e., spurring of tibial spines), eburnation, and osteophytes are considered features of osteoarthritis. This investigation employed direct inspection of the medial and lateral tibial plateaus in paleopathological specimens to analyze the frequency and morphological features of osteoarthritis and to define any relationship between the size of osteophytes and that of the intercondylar tibial spines. A total of 35 tibial bone specimens were evaluated for the degree of osteoarthritis and presence of eburnation. Each plateau was also divided into four quadrants and the presence and size of bone outgrowths were recorded in each quadrant. The ''medial/lateral tibial intercondylar spine index'' for each specimen was calculated as follows: (medial/lateral intercondylar tibial spine height)/(anteroposterior width of the superior tibial surface). The relationships between medial and lateral tibial height indexes with the degree of osteoarthritis were then tested. Osteophytes were observed more frequently in the anterior quadrants of both tibial plateaus than in the posterior quadrants (29 vs 16 for the medial tibial plateau [p = 0.01] and 28 vs 20 for the lateral tibial plateau [p = 0.04]). Eburnation was seen more frequently in the posterior regions of both tibial plateaus than in the anterior regions (17 vs 5, p < 0.01). In specimens with no signs of osteoarthritis the lateral intercondylar tibial index was significantly lower than that in specimens with some degree of osteoarthritis (p = 0.02). The medial intercondylar tibial index of the specimens with no signs of osteoarthritis was not significantly different from that of the specimens with some degree of osteoarthritis (p = 0.45). There was a positive correlation between the lateral spine height index and the overall grading of osteoarthritis, (r = 0.6, p < 0.01). In the anteromedial and posteromedial quadrants of the lateral tibial plateau, the association between the lateral

  2. Femoral nerve damage (image)

    The femoral nerve is located in the leg and supplies the muscles that assist help straighten the leg. It supplies sensation ... leg. One risk of damage to the femoral nerve is pelvic fracture. Symptoms of femoral nerve damage ...

  3. Pseudointercondylar notch sign: manifestation of osteochondritis dissecans of the trochlea

    Pruthi, Sumit; Parnell, Shawn E.; Thapa, Mahesh M.

    2009-01-01

    Osteochondritis dissecans (OCD) is an idiopathic condition affecting the articular epiphysis. Initially described in the knee, this entity affects several other parts of the body such as the talar dome, tarsal navicular, and femoral capital epiphysis. OCD of the elbow primarily involves the capitellum. OCD involving the trochlea has rarely been reported. We describe an unusual and interesting case of OCD affecting the trochlea, mimicking a pseudointercondylar notch. (orig.)

  4. [Treatment of type C intercondylar fractures of distal humerus using dual plating].

    Liu, Ya-Ke; Xu, Hua; Liu, Fan; Wang, You-Hua; Tao, Ran; Cao, Yi; Wang, Hong; Zhou, Zhen-Yu; Zhu, Yong

    2009-06-15

    To evaluate the clinical outcome of dual plating in the treatment of humeral intercondylar type-C fractures in adults. From June 2004 to October 2007, 38 cases of type-C distal humeral fractures were stabilised with dual plating. There were 21 males and 17 females. The average age was 43 years with a range from 21 to 71 years. According to the AO classification, 9 cases were of type C1, 17 of C2 and 12 of C3. The posterior midline approach was selected. Twenty-one cases were exposed through the trans-olecranon osteotomy, 11 through the Campbell (Van Gorder) approach, 6 through triceps sparing approach. Autogenous bone graft was performed in 5 cases because of severe comminution. Thirty-five patients were followed-up for 14-30 months (mean 24.2 months). At the latest follow-up, the elbow flexion averaged 119 degrees (range 90 degrees - 135 degrees ), and the loss of extension averaged 16.2 degrees (range 5 degrees - 25 degrees ). All the patients got bony healing, the average healing period was 14 weeks. The patients were evaluated using the criteria of Aitken and Rorabeek and the scores were 13 excellent, 16 good, 6 fair. Twenty-nine patients (82.9%) had a good or excellent results. Complications included 4 cases of traumatic osteoarthritis, 2 heterotopic ossification, 1 ulnar neuropathy. Infection as well as loosening or breakage of the implant was not found. The dual plating is able to provide rigid fixation for the humeral intercondylar fractures. In addition, it can allow early functional exercise after operation, decrease the related complications significantly, and improve the functional results.

  5. Stress concentration at notches

    Savruk, Mykhaylo P

    2017-01-01

    This book compiles solutions of linear theory of elasticity problems for isotropic and anisotropic bodies with sharp and rounded notches. It contains an overview of established and recent achievements, and presents the authors’ original solutions in the field considered with extensive discussion. The volume demonstrates through numerous, useful examples the effectiveness of singular integral equations for obtaining exact solutions of boundary problems of the theory of elasticity for bodies with cracks and notches. Incorporating analytical and numerical solutions of the problems of stress concentrations in solid bodies with crack-like defects, this volume is ideal for scientists and PhD students dealing with the problems of theory of elasticity and fracture mechanics. Stands as a modern and extensive compendium of solutions to the problems of linear theory of elasticity of isotropic and anisotropic bodies with sharp and rounded notches; Adopts a highly reader-friendly layout of tables, charts, approximation ...

  6. Fracture of the medial intercondylar eminence of the tibia in horses treated by arthroscopic fragment removal (21 horses)

    Rubio‐Martínez, L. M.; Redding, W. R.; Bladon, B.; Wilderjans, H.; Payne, R. J.; Tessier, C.; Geffroy, O.; Parker, R.; Bell, C.; Collingwood, F. A.

    2017-01-01

    Summary Background Fractures of the medial intercondylar eminence of the tibia (MICET) are scarcely reported in horses. Objectives To report the clinical and diagnostic findings, surgical treatment and outcome in a series of horses presented with MICET fracture and treated with arthroscopic fragment removal. Study design Multicentre retrospective case series. Methods Case records of horses diagnosed with MICET fractures that had undergone surgical treatment were reviewed. Follow‐up informatio...

  7. [CLINICAL STUDIES ON EFFECT OF ARTHROSCOPIC INTERCONDYLAR FOSSA ANGIOPLASTY ON ABILITY OF NEUROMUSCULAR CONTROL IN ELDERLY PATIENTS WITH KNEE OSTEOARTHRITIS].

    Huang, Jingmin; Wang, Haijiao; Wu, Jiang; Li, Dongchao; Li, Yuhong

    2015-08-01

    To study the effect of arthroscopic intercondylar fossa angioplasty on the ability of neuromuscular control of the knee joint in elderly patients with knee osteoarthritis (KOA). Between June 2012 and March 2013, 20 elderly patients with KOA and in accordance with inclusion and exclusion criteria underwent arthroscopic intercondylar fossa angioplasty (operation group), and 20 healthy elderly people served as control group. There was no significant difference in age, height, weight, and body mass index between 2 groups (P > 0.05). The proprioception capability (using passive regeneration test at measurement angles of 15, 30, and 60°) and quadriceps mobilization [including maximum voluntary contraction (MVC), central activation ratio (CAR), and activation deficit (AD)] were measured to avaluate the neuromuscular control of the knee; the Lysholm score was used to evaluate knee function. The above indexes were measured to assess the knee neuromuscular control and recovery of joint function in patients of operation group at 3, 6, and 9 months after operation. Compared with the control group, MVC, CAR, and Lysholm scores were significantly decreased, and the AD and passive knee angle difference were significantly increased in operation group (P 0.05). Arthroscopic intercondylar fossa angioplasty can relieve ACL pressure, abrasion, and impact, which will recover the ability of neuromuscular control, increase proprioception and quadriceps mobilization capacity, and improve the joint function.

  8. The Dmp1-SOST Transgene Interacts With and Downregulates the Dmp1-Cre Transgene and the Rosa(Notch) Allele.

    Zanotti, Stefano; Canalis, Ernesto

    2016-05-01

    Activation of Notch1 in osteocytes of Rosa(Notch) mice, where a loxP-flanked STOP cassette and the Nicd coding sequence were targeted to the reverse orientation splice acceptor (Rosa)26 locus, causes osteopetrosis associated with suppressed Sost expression and enhanced Wnt signaling. To determine whether Sost downregulation mediates the effects of Notch activation in osteocytes, Rosa(Notch) mice were crossed with transgenics expressing Cre recombinase or SOST under the control of the dentin matrix protein (Dmp)1 promoter. Dmp1-SOST transgenics displayed vertebral osteopenia and a modest femoral cancellous and cortical bone phenotype, whereas hemizygous Dmp1-Cre transgenics heterozygous for the Rosa(Notch) allele (Dmp1-Cre;Rosa(Notch)) exhibited osteopetrosis. The phenotype of Notch activation in osteocytes was prevented in Dmp1-Cre;Rosa(Notch) mice hemizygous for the Dmp1-SOST transgene. The effect was associated with downregulated Notch signaling and suppressed Dmp1 and Rosa26 expression. To test whether SOST regulates Notch expression in osteocytes, cortical bone cultures from Dmp1-Cre;Rosa(Notch) mice or from Rosa(Notch) control littermates were exposed to recombinant human SOST. The addition of SOST had only modest effects on Notch target gene mRNA levels and suppressed Dmp1, but not Cre or Rosa26, expression. These findings suggest that prevention of the Dmp1-Cre;Rosa(Notch) skeletal phenotype by Dmp1-SOST is not secondary to SOST expression but to interactions among the Dmp1-SOST and Dmp1-Cre transgenes and the Rosa26 locus. In conclusion, the Dmp1-SOST transgene suppresses the expression of the Dmp1-Cre transgene and of Rosa26. © 2015 Wiley Periodicals, Inc.

  9. Band-notched spiral antenna

    Jeon, Jae; Chang, John

    2018-03-13

    A band-notched spiral antenna having one or more spiral arms extending from a radially inner end to a radially outer end for transmitting or receiving electromagnetic radiation over a frequency range, and one or more resonance structures positioned adjacent one or more segments of the spiral arm associated with a notch frequency band or bands of the frequency range so as to resonate and suppress the transmission or reception of electromagnetic radiation over said notch frequency band or bands.

  10. Notch sensitivity of aliphatic polyketone terpolymers

    Zuiderduin, W.C.J.; Huetink, Han; Gaymans, R.J.

    2004-01-01

    The notch sensitivity of aliphatic polyketone (PK) terpolymers was investigated in this article. The notch-tip radius was varied between the size of an actual propagating crack tip of 1-2 m and the largest notch tip of 1000 m radius. The larger notch-tip radii (1000-15 m) were milled into the

  11. Endosomal sorting of Notch receptors through COMMD9-dependent pathways modulates Notch signaling

    Li, Haiying; Koo, Yeon; Mao, Xicheng; Sifuentes-Dominguez, Luis; Morris, Lindsey L.; Jia, Da; Miyata, Naoteru; Faulkner, Rebecca A.; van Deursen, Jan M.; Vooijs, Marc; Billadeau, Daniel D.; van de Sluis, Bart; Cleaver, Orane; Burstein, Ezra

    2015-01-01

    Notch family members are transmembrane receptors that mediate essential developmental programs. Upon ligand binding, a proteolytic event releases the intracellular domain of Notch, which translocates to the nucleus to regulate gene transcription. In addition, Notch trafficking across the

  12. Pixel signal intensity analysis of anterior cruciate ligament grafts in knees with and without intercondylar roof impingement

    Howell, S.M.; Berns, G.S.; Farley, T.E.; Clark, J.A.

    1990-01-01

    This paper determines if intercondylar roof (IR) impingement produces quantitative, regionalized, and time-dependent differences in the pixel signal intensity (PSI) of anterior cruciate ligament (ACL) grafts. Patients with hamstring autografts were placed into two groups: inpinged (n = 14) and unimpinged (n = 18). MR images were obtained at 3, 6, 9, and over 12 months after operation in the unimpinged group and at 22 months in the impinged group. The PSI was measured along the proximal, middle, and distal thirds of the graft. The PSI was greater in the impinged knees in the distal (P < .008) and middle thirds (P < .009) of the graft, but there was no difference in the proximal third. In the unimpinged group, the signal in all three zones did not change from 3 to 12 months after operation. The tibial tunnel placement was more anterior in the impinged knees (P < .001). Stability (P < .012) and knee extension (P < .003) were better in the unimpinged knees

  13. Femoral head avascular necrosis

    Chrysikopoulos, H.; Sartoris, D.J.; Resnick, D.L.; Ashburn, W.; Pretorius, T.

    1988-01-01

    MR imaging has been shown to be more sensitive and specific than planar scintigraphy for avascular necrosis (AVN) of the femoral head. However, experience with single photon emission CT (SPECT) is limited. The authors retrospectively compared 1.5-T MR imaging with SPECT in 14 patients with suspected femoral head AVN. Agreement between MR imaging and SPECT was present in 24 femurs, 14 normal and ten with AVN. MR imaging showed changes of AVN in the remaining four femoral heads. Of these, one was normal and the other three inconclusive for AVN by SPECT. The authors conclude that MR imaging is superior to SPECT for the evaluation of AVN of the hip

  14. ACL graft can replicate the normal ligament's tension curve

    Arnold, MP; Verdonschot, N; van Kampen, A

    2005-01-01

    The anatomical femoral insertion of the normal anterior cruciate ligament (ACL) lies on the deep portion of the lateral wall of the intercondylar fossa. Following the deep bone-cartilage border, it stretches from 11 o'clock high in the notch all the way down to its lowest border at 8 o'clock. The

  15. A technique for reproducible roentgenprograms of the intercondylar sulcus for the study of the femoropatellar

    Koelbel, R.; Bergmann, G.; Rohlmann, A.

    1979-01-01

    Roentgenographic documentation of certain features of FP-joint geometry and orientation may serve as guideline in deciding on the form of treatment for chondromalacia or recurrent patellar dislocation. Reproducible conditions for taking roentgen films are equally important for this purpose as well as for quantitative measurements and possible statistical work. A new positioning device for the patient's legs has been designed utilizing a parallellogram frame. The roentgenographic technique for skyline views at 30 0 , 60 0 and 90 0 inclination of the central beam relative to the femoral axis is described. The advantages over previous techniques are the ease of handling the positioning frame, the need for only vertical and horizontal adjustment of the roentgen tube, independence of the type of tube or table, reproducibility of cassette and patient positioning. (orig.) [de

  16. Notch effects in uniaxial tension specimens

    Delph, T.J.

    1979-03-01

    Results of a literature survey on the effect of notches on the time-dependent failure of uniaxial tension specimens at elevated temperatures are presented. Particular attention is paid to the failure of notched specimens containing weldments

  17. The adhesion force of Notch with Delta and the rate of Notch signaling.

    Ahimou, Francois; Mok, Lee-Peng; Bardot, Boris; Wesley, Cedric

    2004-12-20

    Notch signaling is repeatedly used during animal development to specify cell fates. Using atomic force microscopy on live cells, chemical inhibitors, and conventional analyses, we show that the rate of Notch signaling is linked to the adhesion force between cells expressing Notch receptors and Delta ligand. Both the Notch extracellular and intracellular domains are required for the high adhesion force with Delta. This high adhesion force is lost within minutes, primarily due to the action of Presenilin on Notch. Reduced turnover or Delta pulling accelerate this loss. These data suggest that strong adhesion between Notch and Delta might serve as a booster for initiating Notch signaling at a high rate.

  18. [Effectiveness comparison of suspension fixation plus hinged external fixator and double plate internal fixation in treatment of type C humeral intercondylar fractures].

    Zhang, Jian; Lin, Xu; Zhong, Zeli; Wu, Chao; Tan, Lun

    2017-07-01

    To compare the effectiveness of suspension fixation plus hinged external fixator with double plate internal fixation in the treatment of type C humeral intercondylar fractures. Between January 2014 and April 2016, 30 patients with type C (Association for the Study of Internal Fixation, AO/ASIF) humeral intercondylar fractures were treated. Kirschner wire suspension fixation plus hinged external fixator was used in 14 cases (group A), and double plate internal fixation in 16 cases (group B). There was no significant difference in gender, age, injury cause, disease duration, injury side, and type of fracture between 2 groups ( P >0.05). There was no significant difference in operation time and hospitalization stay between 2 groups ( P >0.05). But the intraoperative blood loss in group A was significantly less than that in group B ( P internal fixation removal, the intraoperative blood loss, and VAS score at 1 day and 3 days after operation in group A were significant better than those in group B ( P external fixator and double plate internal fixation for the treatment of type C humeral intercondylar fractures have ideal outcome in elbow function. But the suspension fixation plus hinged external fixator is better than double plate internal fixation in intraoperative blood loss, postoperative VAS score, and time of internal fixation removal.

  19. Notch Signaling: Piercing a Harness of Simplicity

    Helbig, Christina; Amsen, Derk

    2015-01-01

    The Notch pathway is an attractive therapeutic target for treatment of cancer and T cell-mediated pathology, but Notch inhibition leads to many side effects. Pinnell et al. (2015) demonstrate that oncogenic functions can be separated biochemically from other functions of Notch, opening new options

  20. Notch filters for port-Hamiltonian systems

    Dirksz, D.A.; Scherpen, J.M.A.; van der Schaft, A.J.; Steinbuch, M.

    2012-01-01

    In this paper a standard notch filter is modeled in the port-Hamiltonian framework. By having such a port-Hamiltonian description it is proven that the notch filter is a passive system. The notch filter can then be interconnected with another (nonlinear) port-Hamiltonian system, while preserving the

  1. DOL behaviour of end-notched beams

    Gustafsson, P.J.; Hoffmeyer, Preben; Valentin, G.

    1998-01-01

    The long-term loading strength of end-notched beams made of glulam and LVL was tested. The beams were of various sizes, with and without a moisture sealing at the notch. Tests were conducted in open shelter climates, and at constant and cyclic relative humidity. The short-term strength was tested...... beams with a moisture sealing at the notch...

  2. Notch Signaling and Brain Tumors

    Stockhausen, Marie; Kristoffersen, Karina; Poulsen, Hans Skovgaard

    2011-01-01

    Human brain tumors are a heterogenous group of neoplasms occurring inside the cranium and the central spinal cord. In adults and children, astrocytic glioma and medulloblastoma are the most common subtypes of primary brain tumors. These tumor types are thought to arise from cells in which Notch...

  3. Femoral shaft fractures

    Bender, C.E.; Campbell, D.C. II

    1985-01-01

    The femur is the longest, largest, and strongest bone in the body. Because of its length, width, and role as primary weight-bearing bone, it must tolerate the extremes of axial loading and angulatory stresses. Massive musculature envelopes the femur. This masculature provides abundant blood supply to the bone, which also allows great potential for healing. Thus, the most significant problem relating to femoral shaft fractures is not healing, but restoration of bone length and alignment so that the femoral shaft will tolerate the functional stresses demanded of it

  4. Proximal femoral fractures

    Palm, Henrik; Teixidor, Jordi

    2015-01-01

    searched the homepages of the national heath authorities and national orthopedic societies in West Europe and found 11 national or regional (in case of no national) guidelines including any type of proximal femoral fracture surgery. RESULTS: Pathway consensus is outspread (internal fixation for un...

  5. Case report 486: Spondyloepiphyseal dysplasia tarda (SDT) (presumptively proved)

    Brown, D.D.; Childress, M.H.

    1988-01-01

    A 51 year old man with severe degenerative joint disease, short stature, barrel chest deformity, platyspondyly, a narrow pelvis, small iliac bones, dysplastic femoral heads and necks, notching of the patellae and flattening of the femoral intercondylar notches has been described as an example of Spondyloepiphyseal dysplasia tarda SDT. The entity was discussed in detail. The notching of the patellae has not been reported in association with SDT to the authors' knowledge. Characteristic features of SDT allow it to be differentiated from other arthropathies and dysplasias and these distinctions have been emphasized in the discussion. The diagnosis in this case can only be considered presumptively proved. (orig./MG)

  6. [Trochanteric femoral fractures].

    Douša, P; Čech, O; Weissinger, M; Džupa, V

    2013-01-01

    At the present time proximal femoral fractures account for 30% of all fractures referred to hospitals for treatment. Our population is ageing, the proportion of patients with post-menopausal or senile osteoporosis is increasing and therefore the number of proximal femoral fractures requiring urgent treatment is growing too. In the age category of 50 years and older, the incidence of these fractures has increased exponentially. Our department serves as a trauma centre for half of Prague and part of the Central Bohemia Region with a population of 1 150 000. Prague in particular has a high number of elderly citizens. Our experience is based on extensive clinical data obtained from the Register of Proximal Femoral Fractures established in 1997. During 14 years, 4280 patients, 3112 women and 1168 men, were admitted to our department for treatment of proximal femoral fractures. All patients were followed up until healing or development of complications. In the group under study, 82% were patients older than 70 years; 72% of those requiring surgery were in their seventies and eighties. Men were significantly younger than women (pfractures were 2.3-times more frequent in women than in men. In the category under 60 years, men significantly outnumbered women (pfractures were, on the average, eight years older than the patients with intertrochanteric fractures, which is a significant difference (pTrochanteric fractures accounted for 54.7% and femoral neck fractures for 45.3% of all fractures. The inter-annual increase was 5.9%, with more trochanteric than femoral neck fractures. There was a non-significant decrease in intertrochanteric (AO 31-A3) fractures. On the other hand, the number of pertrochanteric (AO 31-A1+2) fractures increased significantly (pfractures were treated with a proximal femoral nail; a short nail was used in 1260 and a long nail in 134 of them. A dynamic hip screw (DHS) was employed to treat 947 fractures. Distinguishing between pertrochanteric (21-A1

  7. Technical note: Anterior cruciate ligament reconstruction in the presence of an intramedullary femoral nail using anteromedial drilling.

    Lacey, Matthew; Lamplot, Joseph; Walley, Kempland C; DeAngelis, Joseph P; Ramappa, Arun J

    2017-05-18

    To describe an approach to anterior cruciate ligament (ACL) reconstruction using autologous hamstring by drilling via the anteromedial portal in the presence of an intramedullary (IM) femoral nail. Once preoperative imagining has characterized the proposed location of the femoral tunnel preparations are made to remove all of the hardware (locking bolts and IM nail). A diagnostic arthroscopy is performed in the usual fashion addressing all intra-articular pathology. The ACL remnant and lateral wall soft tissues are removed from the intercondylar, to provide adequate visualization of the ACL footprint. Femoral tunnel placement is performed using a transportal ACL guide with desired offset and the knee flexed to 2.09 rad. The Beath pin is placed through the guide starting at the ACL's anatomic footprint using arthroscopic visualization and/or fluoroscopic guidance. If resistance is met while placing the Beath pin, the arthroscopy should be discontinued and the obstructing hardware should be removed under fluoroscopic guidance. When the Beath pin is successfully placed through the lateral femur, it is overdrilled with a 4.5 mm Endobutton drill. If the Endobutton drill is obstructed, the obstructing hardware should be removed under fluoroscopic guidance. In this case, the obstruction is more likely during Endobutton drilling due to its larger diameter and increased rigidity compared to the Beath pin. The femoral tunnel is then drilled using a best approximation of the graft's outer diameter. We recommend at least 7 mm diameter to minimize the risk of graft failure. Autologous hamstring grafts are generally between 6.8 and 8.6 mm in diameter. After reaming, the knee is flexed to 1.57 rad, the arthroscope placed through the anteromedial portal to confirm the femoral tunnel position, referencing the posterior wall and lateral cortex. For a quadrupled hamstring graft, the gracilis and semitendinosus tendons are then harvested in the standard fashion. The tendons are whip

  8. Iodixanol in femoral arteriography

    Thorstensen, Oe.; Albrechtsson, U.; Calissendorff, B.; Larusdottir, H.; Norgren, L.; Tengvar, M.; Bolstad, B.; Aspelin, P.

    1994-01-01

    Two contrast media, iodixanol (Visipaque, Nycomed) 270 mg I/ml and iohexol (Omnipaque, Nycomed) 300 mg I/ml, were compared in femoral arteriography, in 147 patients. Both contrast media were diagnostically effective for use in femoral arteriography, without any significant difference. Pain was reported in connection with injection of iohexol by 36% of the patients, after injection of iodixanol none reported pain. Seventy-two percent of the patients in the iodixanol group reported a sensation of warmth in connection with contrast injection versus 90% in the iohexol group. The average intensity of the warmth was greater with iohexol than with iodixanol. Fourteen percent of patients in the iodixanol group and 1% in the iohexol group reported one or more subjective adverse events. (orig.)

  9. Notch Inhibits Osteoblast Differentiation and Causes Osteopenia

    Zanotti, Stefano; Smerdel-Ramoya, Anna; Stadmeyer, Lisa; Durant, Deena; Radtke, Freddy; Canalis, Ernesto

    2008-01-01

    Notch receptors are determinants of cell fate decisions. To define the role of Notch in the adult skeleton, we created transgenic mice overexpressing the Notch intracellular domain (NICD) under the control of the type I collagen promoter. First-generation transgenics were small and osteopenic. Bone histomorphometry revealed that NICD caused a decrease in bone volume, secondary to a reduction in trabecular number; osteoblast and osteoclast number were decreased. Low fertility of founder mice and lethality of young pups did not allow the complete establishment of transgenic lines. To characterize the effect of Notch overexpression in vitro, NICD was induced in osteoblasts and stromal cells from Rosanotch mice, in which a STOP cassette flanked by loxP sites is upstream of NICD, by transduction with an adenoviral vector expressing Cre recombinase (Cre) under the control of the cytomegalovirus (CMV) promoter (Ad-CMV-Cre). NICD impaired osteoblastogenesis and inhibited Wnt/β-catenin signaling. To determine the effects of notch1 deletion in vivo, mice in which notch1 was flanked by loxP sequences (notch1loxP/loxP) were mated with mice expressing Cre recombinase under the control of the osteocalcin promoter. Conditional null notch1 mice had no obvious skeletal phenotype, possibly because of rescue by notch2; however, 1-month-old females exhibited a modest increase in osteoclast surface and eroded surface. Osteoblasts from notch1loxP/loxP mice, transduced with Ad-CMV-Cre and transfected with Notch2 small interfering RNA, displayed increased alkaline phosphatase activity. In conclusion, Notch signaling in osteoblasts causes osteopenia and impairs osteo-blastogenesis by inhibiting the Wnt/β-catenin pathway. PMID:18420737

  10. Radiographic femoral varus measurement is affected unpredictably by femoral rotation

    Miles, James Edward

    Radiographic measurements of femoral varus are used to determine if intervention to correct femoral deformity is required, and to calculate the required correction. The varus angle is defined as the angle between the proximal femoral long axis (PFLA) and an axis tangential to the distal femoral...... and externally by 5° and 10° using plastic wedges. Accuracy of rotation was within +1°. Digital radiographs were obtained at each position. Varus angles were measured using ImageJ, employing two definitions of PFLA. Mean varus angles increased with 10° of either internal or external rotation with both PFLA...... rotation angles. The effect of rotation on varus angle measurements in these femoral specimens contradicts a previous report using CT. The most probable explanation is the difference in femoral positioning: the CT study used a slightly elevated position compared to that in this study, resulting in better...

  11. The adhesion force of Notch with Delta and the rate of Notch signaling

    Ahimou, Francois; Mok, Lee-Peng; Bardot, Boris; Wesley, Cedric

    2004-01-01

    Notch signaling is repeatedly used during animal development to specify cell fates. Using atomic force microscopy on live cells, chemical inhibitors, and conventional analyses, we show that the rate of Notch signaling is linked to the adhesion force between cells expressing Notch receptors and Delta ligand. Both the Notch extracellular and intracellular domains are required for the high adhesion force with Delta. This high adhesion force is lost within minutes, primarily due to the action of ...

  12. Arthroscopic suture fixation in patients with a tibial intercondylar eminence fracture using a simple device to penetrate the anterior cruciate ligament

    Masato Aratake

    2014-04-01

    Full Text Available Displaced tibial intercondylar eminence fractures require early reduction and stable fixation to prevent nonunion, knee instability, and a lack of extension. Many types of surgical procedure are recommended including arthrotomy or an arthroscopic technique to stabilize the fracture segment using Kirschner wire, screws, staples, and suture fixation. However, contemporary arthroscopic techniques and devices can facilitate intra-articular surgery and have been applied to the treatment of this fracture. In our current report, we describe a simple suture fixation method under arthroscopy for the treatment of tibial intercondylar eminence fractures. We treated eight knees of eight patients. One patient had a Type II fracture and seven patients had a Type III fracture according to Meyer's classification. Following the arthroscopic inspection of concomitant injuries, debridement of hematoma, and reduction of the fragment, two nonabsorbable sutures (Ethibond No. 2, Johnson & Johnson, Somerville, NJ, USA were advanced through the suture passer device, which is used to penetrate the anterior cruciate ligament (ACL near to the insertion site of the displaced fragment. Two surgical sutures were pulled out by the suture retriever from the anterior proximal tibia hole and were fixed to the tibia cortex bone with a double-spike plate. At follow-up, radiographic examinations showed that bone union was achieved in all cases. All but one patient could resume normal activities with no restrictions and no ligamentous instability. All knees had a negative Lachman's test and showed a gain of stable ligament function by KT2000 arthrometer evaluation. One patient had an insignificant extension limitation and experienced slight pain after walking but these symptoms were minimal. In conclusion current arthroscopic surgery techniques for tibial intercondylar fractures can be easily performed and reproducibly achieve secure fixation and early mobilization of the knee.

  13. Eddy current standards - Cracks versus notches

    Hagemaier, D. J.; Collingwood, M. R.; Nguyen, K. H.

    1992-10-01

    Eddy current tests aimed at evaluating cracks and electron-discharge machined (EDM) notches in 7075-T6 aluminum specimens are described. A comparison of the shape and amplitude of recordings made from both transverse and longitudinal scans of small EDM notches and fatigue cracks showd almost identical results. The signal amplitude and phase angle increased with an increase of EDM notch and crak size. It is concluded that equivalent eddy current results obtained from similar-size surface cracks and notches in aluminum can be used to establish a desired sensitivity level for inspection.

  14. Assessment of correlation between knee notch width index and the three-dimensional notch volume

    van Eck, C.F.; Martins, C.A.Q.; Lorenz, S.G.F.; Fu, F.H.; Smolinski, P.

    2010-01-01

    This study was done to determine whether there is a correlation between the notch volume and the notch width index (NWI) as measured on the three most frequently used radiographic views: the Holmblad 45A degrees, Holmblad 70A degrees, and Rosenberg view. The notch volume of 20 cadaveric knees was

  15. The common oncogenomic program of NOTCH1 and NOTCH3 signaling in T-cell acute lymphoblastic leukemia.

    Sung Hee Choi

    Full Text Available Notch is a major oncogenic driver in T cell acute lymphoblastic leukemia (T-ALL, in part because it binds to an enhancer that increases expression of MYC. Here, we exploit the capacity of activated NOTCH1 and NOTCH3 to induce T-ALL, despite substantial divergence in their intracellular regions, as a means to elucidate a broad, common Notch-dependent oncogenomic program through systematic comparison of the transcriptomes and Notch-bound genomic regulatory elements of NOTCH1- and NOTCH3-dependent T-ALL cells. ChIP-seq studies show a high concordance of functional NOTCH1 and NOTCH3 genomic binding sites that are enriched in binding motifs for RBPJ, the transcription factor that recruits activated Notch to DNA. The interchangeability of NOTCH1 and NOTCH3 was confirmed by rescue of NOTCH1-dependent T-ALL cells with activated NOTCH3 and vice versa. Despite remarkable overall similarity, there are nuanced differences in chromatin landscapes near critical common Notch target genes, most notably at a Notch-dependent enhancer that regulates MYC, which correlates with responsiveness to Notch pathway inhibitors. Overall, a common oncogenomic program driven by binding of either Notch is sufficient to maintain T-ALL cell growth, whereas cell-context specific differences appear to influence the response of T-ALL cells to Notch inhibition.

  16. Disadvantages and advantages of transtibial technique for creating the anterior cruciate ligament femoral socket.

    Robin, Brett N; Lubowitz, James H

    2014-10-01

    Anterior cruciate ligament (ACL) femoral socket techniques have distinct advantages and disadvantages when considering the following techniques: transtibial, anteromedial portal, outside-in, and outside-in retroconstruction. There is no one perfect technique and we have an incomplete understanding of anatomical, biomechanical, isometry, stability, and clinical outcomes. Our primary focus is transtibial technique for creating the ACL femoral socket. Advantages include less invasive, isometric graft placement, stable Lachman exam, and minimal graft impingement with the tunnel and notch. Disadvantages include nonanatomic vertical graft placement that can cause rotational instability and positive pivot shift, interference screw divergence, graft-tunnel length mismatch, femoral socket constraint, posterior cruciate ligament impingement, and a short, oblique tibial tunnel that may undermine the medial plateau in an attempt to achieve anatomic ACL reconstruction. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  17. Notching on cancer’s door: Notch signaling in brain tumors

    Marcin eTeodorczyk

    2015-01-01

    Full Text Available Notch receptors play an essential role in the regulation of central cellular processes during embryonic and postnatal development. The mammalian genome encodes for four Notch paralogs (Notch 1-4, which are activated by three Delta-like (Dll1/3/4 and two Serrate-like (Jagged1/2 ligands. Further, non-canonical Notch ligands such as EGFL7 have been identified and serve mostly as antagonists of Notch signaling. The Notch pathway prevents neuronal differentiation in the central nervous system by driving neural stem cell maintenance and commitment of neural progenitor cells into the glial lineage. Notch is therefore often implicated in the development of brain tumors, as tumor cells share various characteristics with neural stem and progenitor cells. Notch receptors are overexpressed in gliomas and their oncogenicity has been confirmed by gain- and loss-of-function studies in vitro and in vivo. To this end, special attention is paid to the impact of Notch signaling on stem-like brain tumor-propagating cells as these cells contribute to growth, survival, invasion and recurrence of brain tumors. Based on the outcome of ongoing studies in vivo, Notch-directed therapies such as γ secretase inhibitors and blocking antibodies have entered and completed various clinical trials. This review summarizes the current knowledge on Notch signaling in brain tumor formation and therapy.

  18. Evidence of non-canonical NOTCH signaling

    Traustadóttir, Gunnhildur Ásta; Jensen, Charlotte H; Thomassen, Mads

    2016-01-01

    Dlk1(+/+) and Dlk1(-/-) mouse tissues at E16.5, we demonstrated that several NOTCH signaling pathways indeed are affected by DLK1 during tissue development, and this was supported by a lower activation of NOTCH1 protein in Dlk1(+/+) embryos. Likewise, but using a distinct Dlk1-manipulated (si...

  19. Fracture of the medial intercondylar eminence of the tibia in horses treated by arthroscopic fragment removal (21 horses).

    Rubio-Martínez, L M; Redding, W R; Bladon, B; Wilderjans, H; Payne, R J; Tessier, C; Geffroy, O; Parker, R; Bell, C; Collingwood, F A

    2018-01-01

    Fractures of the medial intercondylar eminence of the tibia (MICET) are scarcely reported in horses. To report the clinical and diagnostic findings, surgical treatment and outcome in a series of horses presented with MICET fracture and treated with arthroscopic fragment removal. Multicentre retrospective case series. Case records of horses diagnosed with MICET fractures that had undergone surgical treatment were reviewed. Follow-up information was obtained from re-examination visits and/or owners. Twenty-one cases were identified at 9 equine hospitals between 2004 and 2016. A history of trauma and acute onset of lameness was reported in 12 horses. All cases underwent fracture removal via arthroscopy of the medial femorotibial joint. The cranial cruciate ligament was intact in 6 horses and damaged in 15 horses (damage was ≤25% [n = 9], 25-50% [n = 4] or ≥50% [n = 2] of the cross-sectional area). The cranial ligament of the medial meniscus was damaged in 11 horses (≤25% [n = 8], 25-50% [n = 3]). The medial meniscus was damaged in 5 horses and articular cartilage damage was identified in 14 horses (mild [n = 8], moderate [n = 6]). Follow-up information (median 14 months; 4 months-6 years) was available for 20 cases; 2 horses were sound but convalescing; 13 horses were sound and returned to their previous or expected use. Of the 4 horses with the most severe changes to the articular soft tissue structures, 2 remained lame and 2 were subjected to euthanasia because of persistent lameness. The retrospective, multicentre nature of this study and the limited number of horses are the main limitations. Fractures of the MICET are commonly associated with a traumatic event. Prompt diagnosis and early arthroscopic removal of the fracture are recommended. © 2017 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.

  20. Management of a type two avulsion fracture of the tibial intercondylar eminence in children: arthroscopic suture fixation versus conservative immobilization.

    Zhao, Chen; Bi, Qing; Bi, Mingguang

    2018-06-01

    Treatment of a type II tibial eminence avulsion fracture was controversial. The aim of this study was to compare the clinical outcomes of a modified arthroscopic suture fixation versus conservative immobilization in treatment of this type fracture in immature population. A total of 43 type II avulsion fractures of tibial intercondylar eminence in immature patients were retrospectively enrolled in the study. Twenty-two (13 males, 9 females) were treated with arthroscopic suture fixation and 21(12 males, 9 females) with conservative cast immobilization. Radiograph, Lachman test, anterior drawer test (ADT), International Knee Documentation Committee (IKDC) 2000 subjective score, and Lysholm score were used to evaluate clinical outcomes in follow-up. All 43 paediatric or adolescent patients with a mean of 11.3 years (range, 8-16 years) were followed up for a median period of 34.5 months (range, 24-46 months). Radiographic evaluation showed optimal reduction immediately after surgery and bone union within three months. At the final follow-up, no limitation of knee motion range was found in any children. Grade II laxity was found in one case from surgical group and six from conservation group, showing significant difference based on ADT (χ2 = 7.927, P = 0.005) and Lachman tests (χ2 = 9.546, P = 0.002). IKDC and Lysholm scores were significantly improved; however, there were significant differences in the IKDC score (91.7 ± 4.34 vs. 84.7 ± 6.11, t = 4.35, P < 0.001) and Lysholm score (93.4 ± 4.04 vs. 87.1 ± 5.24, t = 4.53, P < 0.001), and the improvement of IKDC value (40.2 ± 7.83 vs. 31.4 ± 8.4, t = 3.57, P = 0.001) and Lysholm value (43.8 ± 6.55 vs. 35.4 ± 5.97, t = 4.36, P < 0.001) between the surgical group and the nonsurgical group. In treatment of type II tibial eminence avulsion fracture, a modified, 8 shape suture fixation under arthroscopy showed superior clinical

  1. Characterization of Notch1 antibodies that inhibit signaling of both normal and mutated Notch1 receptors.

    Miguel Aste-Amézaga

    2010-02-01

    Full Text Available Notch receptors normally play a key role in guiding a variety of cell fate decisions during development and differentiation of metazoan organisms. On the other hand, dysregulation of Notch1 signaling is associated with many different types of cancer as well as tumor angiogenesis, making Notch1 a potential therapeutic target.Here we report the in vitro activities of inhibitory Notch1 monoclonal antibodies derived from cell-based and solid-phase screening of a phage display library. Two classes of antibodies were found, one directed against the EGF-repeat region that encompasses the ligand-binding domain (LBD, and the second directed against the activation switch of the receptor, the Notch negative regulatory region (NRR. The antibodies are selective for Notch1, inhibiting Jag2-dependent signaling by Notch1 but not by Notch 2 and 3 in reporter gene assays, with EC(50 values as low as 5+/-3 nM and 0.13+/-0.09 nM for the LBD and NRR antibodies, respectively, and fail to recognize Notch4. While more potent, NRR antibodies are incomplete antagonists of Notch1 signaling. The antagonistic activity of LBD, but not NRR, antibodies is strongly dependent on the activating ligand. Both LBD and NRR antibodies bind to Notch1 on human tumor cell lines and inhibit the expression of sentinel Notch target genes, including HES1, HES5, and DTX1. NRR antibodies also strongly inhibit ligand-independent signaling in heterologous cells transiently expressing Notch1 receptors with diverse NRR "class I" point mutations, the most common type of mutation found in human T-cell acute lymphoblastic leukemia (T-ALL. In contrast, NRR antibodies failed to antagonize Notch1 receptors bearing rare "class II" or "class III" mutations, in which amino acid insertions generate a duplicated or constitutively sensitive metalloprotease cleavage site. Signaling in T-ALL cell lines bearing class I mutations is partially refractory to inhibitory antibodies as compared to cell

  2. Flexing and downsizing the femoral component is not detrimental to patellofemoral biomechanics in posterior-referencing cruciate-retaining total knee arthroplasty.

    Marra, Marco A; Strzelczak, Marta; Heesterbeek, Petra J C; van de Groes, Sebastiaan A W; Janssen, Dennis; Koopman, Bart F J M; Verdonschot, Nico; Wymenga, Ate B

    2018-03-20

    When downsizing the femoral component to prevent mediolateral overhang, notching of the anterior femoral cortex may occur, which could be solved by flexing the femoral component. In this study, we investigated the effect of flexion of the femoral component on patellar tendon moment arm, patellofemoral forces and kinematics in posterior-referencing CR-TKA. Our hypothesis was that flexion of the femoral component increases the patellar tendon moment arm, reduces the patellofemoral forces and provides stable kinematics. A validated musculoskeletal model of CR-TKA was used. The flexion of the femoral component was increased in four steps (0°, 3°, 6°, 9°) using posterior referencing, and different alignments were analysed in combination with three implant sizes (3, 4, 5). A chair-rising trial was analysed using the model, while simultaneously estimating quadriceps muscle force, patellofemoral contact force, tibiofemoral and patellofemoral kinematics. Compared to the reference case (size 4 and 0° flexion), for every 3° of increase in flexion of the femoral component the patellar tendon moment arm increased by 1% at knee extension. The peak quadriceps muscle force and patellofemoral contact force decreased by 2%, the patella shifted 0.8 mm more anteriorly and the remaining kinematics remained stable, with knee flexion. With the smaller size, the patellar tendon moment arm decreased by 6%, the quadriceps muscle force and patellofemoral contact force increased by 8 and 12%, and the patellar shifted 5 mm more posteriorly. Opposite trends were found with the bigger size. Flexing the femoral component with posterior referencing reduced the patellofemoral contact forces during a simulated chair-rising trial with a patient-specific musculoskeletal model of CR-TKA. There seems to be little risk when flexing and downsizing the femoral component, compared to when using a bigger size and neutral alignment. These findings provide relevant information to surgeons who wish to

  3. Notch and the awesome power of genetics.

    Greenwald, Iva

    2012-07-01

    Notch is a receptor that mediates cell-cell interactions in animal development, and aberrations in Notch signal transduction can cause cancer and other human diseases. Here, I describe the major advances in the Notch field from the identification of the first mutant in Drosophila almost a century ago through the elucidation of the unusual mechanism of signal transduction a little over a decade ago. As an essay for the GENETICS Perspectives series, it is my personal and critical commentary as well as an historical account of discovery.

  4. Custom-made lateral femoral hemiarthroplasty for traumatic bone loss: A case report.

    Stuyts, Bart; Peersman, Geert; Thienpont, Emmanuel; Van den Eeden, Elke; Van der Bracht, Hans

    2015-10-01

    We report the case of a 32-year-old male patient involved in a road traffic accident in which he sustained a grade II open supra- and intercondylar fracture of the left distal femur with substantial bone loss of the lateral femoral condyle and trochlea (AO classification type 33 C3). Normal knee function was no longer possible, as the patella was trapped within the bony defect. Existing reconstructive options such as unicondylar osteoarticular allograft, arthrodesis, and arthroplasty were considered. However, as all these techniques present significant disadvantages, particularly in young and active patients, a custom-made lateral hemiarthroplasty was designed and implanted as an alternative treatment. Follow-up at 24 months revealed an excellent, pain-free level of function and radiographs showed no signs of implant loosening or migration. This technique offers the most anatomical means of reconstruction with maximal preservation of the bone stock, thereby better facilitating any revisions that may be necessary in the future. This is an experimental technique reserved for rare indications, and currently has no long-term follow-up results associated with its use. Additional research is therefore needed before widespread adoption of this technique can take place. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Focal femoral condyle resurfacing.

    Brennan, S A

    2013-03-01

    Focal femoral inlay resurfacing has been developed for the treatment of full-thickness chondral defects of the knee. This technique involves implanting a defect-sized metallic or ceramic cap that is anchored to the subchondral bone through a screw or pin. The use of these experimental caps has been advocated in middle-aged patients who have failed non-operative methods or biological repair techniques and are deemed unsuitable for conventional arthroplasty because of their age. This paper outlines the implant design, surgical technique and biomechanical principles underlying their use. Outcomes following implantation in both animal and human studies are also reviewed. Cite this article: Bone Joint J 2013;95-B:301-4.

  6. Notch and VEGF Interactions in Breast Cancer

    Shawber, Carrie J

    2006-01-01

    The proposal objective is to define Notch and VEGFR-3 in breast cancer. We investigated this relationship in primary endothelial cell cultures, mouse embryos, human breast tumors, and mouse mammary tumor xenografts...

  7. Notch signaling in embryology and cancer

    Reichrath, J; Reichrath, Sandra

    2012-01-01

    "The goal of this volume is to comprehensively cover a highly readable overview on our present knowledge of the role of Notch signalling for embryology and cancer, with a focus on new findings in molecular biology...

  8. Femoral cartilage thickness measurements in healthy individuals: learning, practicing and publishing with TURK-MUSCULUS.

    Özçakar, Levent; Tunç, Hakan; Öken, Öznur; Ünlü, Zeliha; Durmuş, Bekir; Baysal, Özlem; Altay, Zuhal; Tok, Fatih; Akkaya, Nuray; Doğu, Beril; Çapkın, Erhan; Bardak, Ayşenur; Çarlı, Alparslan Bayram; Buğdaycı, Derya; Toktaş, Hasan; Dıraçoğlu, Demirhan; Gündüz, Berrin; Erhan, Belgin; Kocabaş, Hilal; Erden, Gül; Günendi, Zafer; Kesikburun, Serdar; Omaç, Özlem Köroğlu; Taşkaynatan, Mehmet Ali; Şenel, Kazım; Uğur, Mahir; Yalçınkaya, Ebru Yılmaz; Öneş, Kadriye; Atan, Çiğdem; Akgün, Kenan; Bilgici, Ayhan; Kuru, Ömer; Özgöçmen, Salih

    2014-01-01

    Measurement of the femoral cartilage thickness by using in-vivo musculoskeletal ultrasonography (MSUS) has been previously shown to be a valid and reliable method in previous studies; however, to our best notice, normative data has not been provided before in the healthy population.The aim of our study was to provide normative data regarding femoral cartilage thicknesses of healthy individuals with collaborative use of MSUS. This is across-sectional study run at Physical and Rehabilitation Medicine Departments of 18 Secondary and Tertiary Centers in Turkey. 1544 healthy volunteers (aged between 25-40 years) were recruited within the collaboration of TURK-MUSCULUS (Turkish Musculoskeletal Ultrasonography Study Group). Subjects who had a body mass index value of less than 30 and who did not have signs and symptoms of any degenerative/inflammatory arthritis or other rheumatic diseases, history of knee trauma and previous knee surgery were enrolled. Ultrasonographic measurements were performed axially from the suprapatellar window by using linear probes while subjects' knees were in maximum flexion. Three (mid-point) measurements were taken from both knees (lateral condyle, intercondylar area, medial condyle). A total of 2876 knees (of 817 M, 621 F subjects) were taken into analysis after exclusion of inappropriate images. Mean cartilage thicknesses were significantly lower in females than males (all p< 0.001). Thickness values negatively correlated with age; negatively (females) and positively (males) correlated with smoking. Men who regularly exercised had thicker cartilage than who did not exercise (all p < 0.05). Increased age (in both sexes) and absence of exercise (males) were found to be risk factors for decreased cartilage thicknesses. Further data pertaining to other countries would be interesting to uncover whether ethnic differences also affect cartilage thickness. Collaborative use of MSUS seems to be promising in this regard.

  9. Effect of notch dimension on the fatigue life of V-notched structure

    Cheng Changzheng; Naman, Recho; Niu Zhongrong; Zhou Huanlin

    2011-01-01

    Highlights: → A novel method is proposed to calculate the SIFs of crack at notch tip. → Effect of notch opening angle on the crack extension and propagation is studied. → Influence of notch depth on the crack extension and propagation is analyzed. → The fatigue life of a welded joint is analyzed by the present method. - Abstract: The stress singularity degree associated to a V-notch has a great influence on the fatigue life of V-notched structure. The growth rate of the crack initiated at the tip of a V-notch depends on the stress singularity of the V-notch. The fatigue life accompanying with this small crack will represent a large amount of the total fatigue life. In this work, boundary element method (BEM) is used to study the propagation of the crack emanating from a V-notch tip under fatigue loading. A comparison of the fatigue life between the crack initiated from V-notch tip and a lateral crack is done by a crack propagation law until these two cracks have the same stress intensity factors (SIFs). The effect of initial crack length, notch opening angle and notch depth on the crack extension and propagation is analyzed. As an example of engineering application, the fatigue life of a welded joint is investigated by the present method. The influence of weld toe angle and initial crack length on the fatigue life of the welded structure is studied. Some suggestions are given as an attempt to improve the fatigue life of welded structures at the end.

  10. Femoral head necrosis; Hueftkopfnekrose

    Kramer, J.; Scheurecker, G.; Scheurecker, A.; Stoeger, A.; Huber, A. [Roentgeninstitut am Schillerpark, Linz (Austria); Hofmann, S. [Orthopaedisches Landeskrankenhaus Stolzalpe (Austria)

    2009-05-15

    The epidemiology and pathohistogenesis of avascular femoral head necrosis has still not been clarified in detail. Because the course of the disease runs in stages and over a long time period nearly always culminates in the necessity for a total hip prosthesis, an exact radiological evaluation is of paramount importance for the treatment. There is a need for a common staging system to enable comparison of different therapy concepts and especially their long-term results. In this article the ARCO staging system is described in full detail, which includes all radiological modalities as well as histopathological alterations. (orig.) [German] Bei der avaskulaeren Femurkopfnekrose handelt es sich um ein Krankheitsbild, dessen Ursachen noch immer nicht vollstaendig geklaert sind. Da die Erkrankung stadienhaft verlaeuft und ueber einen laengeren Zeitraum betrachtet nahezu immer in einem prothetischen Hueftersatz muendet, ist eine genaue radiologische Abklaerung fuer die Behandlung von enormer Bedeutung. Um Langzeiterfolge verschiedener Therapiekonzepte vergleichen zu koennen, sind eine exakte Beschreibung und darauf basierend die Verwendung einer einheitlichen Stadieneinteilung wuenschenswert. In der vorliegenden Arbeit wird die ARCO-Stadieneinteilung im Detail beschrieben, die alle bildgebenden Methoden beruecksichtigt und histopathologische Veraenderungen mit einbezieht. (orig.)

  11. PKCζ regulates Notch receptor routing and activity in a Notch signaling-dependent manner

    Sjöqvist, M.; Antfolk, D.; Ferraris, S.; Rraklli, V.; Haga, C.; Antila, C.; Mutvei, A.; Imanishi, S.Y.; Holmberg, J.; Jin, S.; Eriksson, J.E.; Lendahl, U.; Sahlgren, C.M.

    Activation of Notch signaling requires intracellular routing of the receptor, but the mechanisms controlling the distinct steps in the routing process is poorly understood. We identify PKCζ as a key regulator of Notch receptor intracellular routing. When PKCζ was inhibited in the developing chick

  12. Posterior Femoral Single Limb Osteotomy for the Removal of Well-Fixed Modular Femoral Neck Components

    Keith A Fehring

    2017-07-01

    Full Text Available Modular neck femoral components were introduced to optimize femoral neck anteversion, leg length, offset, and stability in total hip arthroplasty. However, concerns have been raised in recent years regarding early failure of these implants due to corrosion, pseudotumor, as well as fracture of the modular neck. Removing modular neck femoral implants is challenging as removal of the modular femoral neck leaves a proximally coated femoral stem level with the proximal bone of the femoral neck. We describe a posterior femoral single limb osteotomy  (posterior cut of an extended trochanteric osteotomy for the removal of a modular neck femoral component.

  13. Femoral revision with impaction allografting and an uncemented femoral component

    Nickelsen, T N; Erenbjerg, M; Retpen, J B

    2008-01-01

    A technique for uncemented revision of the femoral component which combines impaction allografting and the use of a long-stemmed proximally coated titanium prostheses (Bimetric, Biomet Inc.) is described. The results after a mean follow-up of 112 months are reported. From 1991 to 1995 femoral...... implants 88% had no pain, 10% had slight pain and only 2% had severe pain. Thirty-eight patients had radiographic signs of remodelling of the graft and/or cortical repair. In cases with a successful outcome, the results have been encouraging in relation to clinical performance, regeneration of bone...

  14. The cyclops lesion after bicruciate-retaining total knee replacement

    Klaassen, Mark A.; Aikins, Jerry L.

    2017-01-01

    The cyclops lesion is a localized anterior arthrofibrosis most commonly seen following anterior cruciate ligament reconstruction. The lesion forms at the anterior cruciate ligament insertion creating a painful extension block between femoral intercondylar notch and tibial plateau. We present 2 cases (3 knees) in which cyclops lesions appeared atypically following bicruciate-retaining total knee replacement. Two lesions occurred in a single patient following bilateral knee replacement. One les...

  15. Fracture toughness evaluation of small notched specimen in consideration of notch effect and loading rate

    Lee, Baik Woo; Kwon, Dong Il; Jang, Jae Il

    2000-01-01

    Notch effect and loading rate dependency on fracture toughness were considered when evaluating fracture toughness of small notched specimens using the instrumented impact test. Notch effect was analyzed into stress redistribution effect and stress relaxation with a viewpoint of stress triaxiality. Stress redistribution effect was corrected by introducing effective crack length, which was the sum of actual crack length and plastic zone size. Stress relaxation effect was also corrected using elastic stress concentration factor, which would decrease if plastic deformation occurred. As a result, corrected fracture toughness of the notched specimen was very consistent with the reference fracture toughness obtained using precracked specimen. In addition, limiting notch root radius, below which fracture toughness was independent of notch radius, was observed and discussed. Loading rate dependency on fracture toughness, which was obtained from the static three point bending test and the instrumented impact test, was also discussed with stress field in plastic zone ahead of a notch and fracture based on stress control mechanism. (author)

  16. Compact microstrip bandpass filter with tunable notch

    Christensen, Silas; Zhurbenko, Vitaliy; Johansen, Tom Keinicke

    2014-01-01

    Two different designs combining a bandpass and a notch filter are developed to operate in the receiving band from 350–470 MHz. The bandpass filter is designed from a simple structure, by use of only four short circuited stubs and a half wavelength transmission line connecting the stubs. The tunable...... notch filter ensures an attenuation level of 19.3 dB to 27.3 dB in the frequency range from 360–480 MHz. The measured passband ripple of the combined filter is less than 0.5 dB, while the insertion loss for the simplest design is less than 1.7 dB only 10 MHz from the notch frequency. Even though...... the wavelength on the selected substrate (εr = 3.55) is approximately 45 cm, the outer dimensions of the final filter only measure 10×10 cm2....

  17. Magnetoresistance effect in permalloy nanowires with various types of notches

    Y. Gao

    2018-05-01

    Full Text Available Suppressing the stochastic domain wall (DW motion in magnetic nanowires is of great importance for designing DW-related spintronic devices. In this work, we have investigated the pinning/depinning processes of DWs in permalloy nanowires with three different types of notches by using longitudinal magnetoresistance (MR measurement. The averaged MR curves demonstrate that the stochastic DW depinning is suppressed partly or even completely by a transversely asymmetric notch. The single-shot MR curves show that how the resistance changes with the applied field also depends strongly on the notch type while the DW is pinned around the notch. In the case of two depinning fields, larger (smaller change of resistance always corresponds to larger (smaller depinning field, regardless of the notch type. These phenomena can be understood by that the spin structure around the notch changes differently with the notch type when the DW is traveling through the notch.

  18. Magnetoresistance effect in permalloy nanowires with various types of notches

    Gao, Y.; You, B.; Wang, J.; Yuan, Y.; Wei, L. J.; Tu, H. Q.; Zhang, W.; Du, J.

    2018-05-01

    Suppressing the stochastic domain wall (DW) motion in magnetic nanowires is of great importance for designing DW-related spintronic devices. In this work, we have investigated the pinning/depinning processes of DWs in permalloy nanowires with three different types of notches by using longitudinal magnetoresistance (MR) measurement. The averaged MR curves demonstrate that the stochastic DW depinning is suppressed partly or even completely by a transversely asymmetric notch. The single-shot MR curves show that how the resistance changes with the applied field also depends strongly on the notch type while the DW is pinned around the notch. In the case of two depinning fields, larger (smaller) change of resistance always corresponds to larger (smaller) depinning field, regardless of the notch type. These phenomena can be understood by that the spin structure around the notch changes differently with the notch type when the DW is traveling through the notch.

  19. Biochemical characterization and cellular effects of CADASIL mutants of NOTCH3.

    He Meng

    Full Text Available Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL is the best understood cause of dominantly inherited stroke and results from NOTCH3 mutations that lead to NOTCH3 protein accumulation and selective arterial smooth muscle degeneration. Previous studies show that NOTCH3 protein forms multimers. Here, we investigate protein interactions between NOTCH3 and other vascular Notch isoforms and characterize the effects of elevated NOTCH3 on smooth muscle gene regulation. We demonstrate that NOTCH3 forms heterodimers with NOTCH1, NOTCH3, and NOTCH4. R90C and C49Y mutant NOTCH3 form complexes which are more resistant to detergents than wild type NOTCH3 complexes. Using quantitative NOTCH3-luciferase clearance assays, we found significant inhibition of mutant NOTCH3 clearance. In coculture assays of NOTCH function, overexpressed wild type and mutant NOTCH3 significantly repressed NOTCH-regulated smooth muscle transcripts and potently impaired the activity of three independent smooth muscle promoters. Wildtype and R90C recombinant NOTCH3 proteins applied to cell cultures also blocked canonical Notch fuction. We conclude that CADASIL mutants of NOTCH3 complex with NOTCH1, 3, and 4, slow NOTCH3 clearance, and that overexpressed wild type and mutant NOTCH3 protein interfere with key NOTCH-mediated functions in smooth muscle cells.

  20. Fatigue crack growth from blunt notches

    Rhodes, D.

    1982-01-01

    A number of methods have been proposed, by which the formation and early growth of fatigue cracks at blunt notches may be predicted. In this report, four methods are compared - i.e. analysis of the crack tip plastic deformation, the cyclic contour integral, δJ, the strain in a critical volume of material, and the notch root plastic strain range. It is shown that these approaches have fundamental elements in common, and that all are compatable with linear elastic fracture mechanics. Early results from a continuing experimental programme are reported. (orig.) [de

  1. Notch-strengthening in two-dimensional foams

    Onck, P.R.

    Metallic foams show notch-strengthening behavior when analyzing double-edge notched specimen in compression and tension. A discrete microstructural model has been used to simulate the effect of notch depth and specimen size on the net-section-strength. The non-uniform deformation behavior is

  2. Proteolytic regulation of Notch1 receptor activity in cancer

    van Tetering, Geert

    2011-01-01

    The Notch receptor is part of a highly conserved signaling pathway essential in development and disease in embryos and adults. Notch proteins coordinate cell-cell communication through receptor-ligand interactions between adjacent cells. First Notch is cleaved in the Golgi by furin at Site-1 (S1)

  3. In vivo analysis of the Notch receptor S1 cleavage.

    Robert J Lake

    2009-08-01

    Full Text Available A ligand-independent cleavage (S1 in the extracellular domain of the mammalian Notch receptor results in what is considered to be the canonical heterodimeric form of Notch on the cell surface. The in vivo consequences and significance of this cleavage on Drosophila Notch signaling remain unclear and contradictory. We determined the cleavage site in Drosophila and examined its in vivo function by a transgenic analysis of receptors that cannot be cleaved. Our results demonstrate a correlation between loss of cleavage and loss of in vivo function of the Notch receptor, supporting the notion that S1 cleavage is an in vivo mechanism of Notch signal control.

  4. Role of Notch signaling in the mammalian heart

    Zhou, X.L.; Liu, J.C. [Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Donghu District, Nanchang, Jiangxi (China)

    2013-12-12

    Notch signaling is an evolutionarily ancient, highly conserved pathway important for deciding cell fate, cellular development, differentiation, proliferation, apoptosis, adhesion, and epithelial-to-mesenchymal transition. Notch signaling is also critical in mammalian cardiogenesis, as mutations in this signaling pathway are linked to human congenital heart disease. Furthermore, Notch signaling can repair myocardial injury by promoting myocardial regeneration, protecting ischemic myocardium, inducing angiogenesis, and negatively regulating cardiac fibroblast-myofibroblast transformation. This review provides an update on the known roles of Notch signaling in the mammalian heart. The goal is to assist in developing strategies to influence Notch signaling and optimize myocardial injury repair.

  5. Inhibitory role of Notch1 in calcific aortic valve disease.

    Asha Acharya

    Full Text Available Aortic valve calcification is the most common form of valvular heart disease, but the mechanisms of calcific aortic valve disease (CAVD are unknown. NOTCH1 mutations are associated with aortic valve malformations and adult-onset calcification in families with inherited disease. The Notch signaling pathway is critical for multiple cell differentiation processes, but its role in the development of CAVD is not well understood. The aim of this study was to investigate the molecular changes that occur with inhibition of Notch signaling in the aortic valve. Notch signaling pathway members are expressed in adult aortic valve cusps, and examination of diseased human aortic valves revealed decreased expression of NOTCH1 in areas of calcium deposition. To identify downstream mediators of Notch1, we examined gene expression changes that occur with chemical inhibition of Notch signaling in rat aortic valve interstitial cells (AVICs. We found significant downregulation of Sox9 along with several cartilage-specific genes that were direct targets of the transcription factor, Sox9. Loss of Sox9 expression has been published to be associated with aortic valve calcification. Utilizing an in vitro porcine aortic valve calcification model system, inhibition of Notch activity resulted in accelerated calcification while stimulation of Notch signaling attenuated the calcific process. Finally, the addition of Sox9 was able to prevent the calcification of porcine AVICs that occurs with Notch inhibition. In conclusion, loss of Notch signaling contributes to aortic valve calcification via a Sox9-dependent mechanism.

  6. Significance of a notch in the otoacoustic emission stimulus spectrum.

    Grenner, J

    2012-09-01

    To explain a clinical observation: a notch in the stimulus spectrum during transient evoked otoacoustic emission measurement in ears with secretory otitis media. The effects of tympanic under-pressure were investigated using a pressure chamber. A model of the ear canal was also studied. Tympanic membrane reflectance increased as a consequence of increased stiffness, causing a notch in the stimulus spectrum. In an adult, the notch could be clearly distinguished at an under-pressure of approximately -185 daPa. The sound frequency of the notch corresponded to a wavelength four times the ear canal length. The ear canal of infants was too short to cause a notch within the displayed frequency range. The notch was demonstrated using both Otodynamics and Madsen equipment. A notch in the otoacoustic emission stimulus spectrum can be caused by increased stiffness of the tympanic membrane, raising suspicion of low middle-ear pressure or secretory otitis media. This finding is not applicable to infants.

  7. Instantaneous center of motion and velocity vector in stifle of dogs undergoing intercondylar notchplasty and articular repair following transection of the cranial cruciate ligament

    Selmi, A.L.; Padilha Filho, J.G.; Lins, B.T.; Mendes, G.M.; Eimantas, G.C.

    2007-01-01

    The instantaneous center of motion (ICM) and velocity vector (Vv), after transection of the cranial cruciate ligament (CCL) followed by a fascial strip reconstruction in association with intercondylar notchplasty (IN), were studied in nine adult dogs. The right stifle was submitted to IN followed by fascial strip reconstruction of the CCL (GI) while in the left stifle IN was not performed (GC). Dogs were evaluated the day prior to surgery, immediately after surgery and at 30, 90 and 180 days postoperatively (po), time at which a subgroup of three dogs were euthanatized. The ICM and resulting Vv were determined by radiographic examination of the stifle. All the stifles presented normally positioned ICM and Vv before surgery. No changes were observed in ICM or Vv in all stifles following intra-articular repair, in association or not with IN, throughout the evaluation period, despite the fact that three dogs in GC and two in GI presented a positive cranial drawer sign immediately following surgery, two dogs in GC and GI at 30 days po, and one single dog in each group thereafter until 180 days po. It is concluded that articular repair, in association with IN or not, did not alter stifle biomechanics, in respect to ICM and Vv [pt

  8. Notch3 signalling promotes tumour growth in colorectal cancer.

    Serafin, Valentina; Persano, Luca; Moserle, Lidia; Esposito, Giovanni; Ghisi, Margherita; Curtarello, Matteo; Bonanno, Laura; Masiero, Massimo; Ribatti, Domenico; Stürzl, Michael; Naschberger, Elisabeth; Croner, Roland S; Jubb, Adrian M; Harris, Adrian L; Koeppen, Hartmut; Amadori, Alberto; Indraccolo, Stefano

    2011-08-01

    Increased Notch1 activity has been observed in intestinal tumours, partially accomplished by β-catenin-mediated up-regulation of the Notch ligand Jagged-1. Whether further mechanisms of Notch activation exist and other Notch receptors might be involved is unclear. Microarray data indicated that Notch3 transcript levels are significantly up-regulated in primary and metastatic CRC samples compared to normal mucosa. Moreover, Notch3 protein was expressed at strong/moderate levels by 19.7% of 158 CRC samples analysed, and at weak levels by 51.2% of the samples. Intrigued by these findings, we sought to investigate whether Notch3 modulates oncogenic features of CRC cells. By exploiting xenografts of CRC cells with different tumourigenic properties in mice, we found that the aggressive phenotype was associated with altered expression of components of the Notch pathway, including Notch3, Delta-like 4 (DLL4), and Jagged-1 ligands. Stimulation with immobilized recombinant DLL4 or transduction with DLL4-expressing vectors dramatically increased Notch3 expression in CRC cells, associated with accelerated tumour growth. Forced expression of an active form of Notch3 mirrored the effects of DLL4 stimulation and increased tumour formation. Conversely, attenuation of Notch3 levels by shRNA resulted in perturbation of the cell cycle followed by reduction in cell proliferation, clonogenic capacity, and inhibition of tumour growth. Altogether, these findings indicate that Notch3 can modulate the tumourigenic properties of CRC cells and contributes to sustained Notch activity in DLL4-expressing tumours. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  9. Mammary and femoral hydatid cysts.

    Shamim, Muhammad

    2010-08-01

    Hydatid cyst disease most commonly affects liver and lungs, but it can affect all viscera and soft tissues of the body. Simultaneous mammary and femoral hydatid cysts, without any other visceral involvement, are extremely rare. This is a case report of 25-years-old female, presenting with lump in left breast mimicking fibroadenoma and lump in right thigh mimicking fibroma. Both turned out to be hydatid cysts.

  10. Frequency and distribution of Notch mutations in tumor cell lines

    Mutvei, Anders Peter; Fredlund, Erik; Lendahl, Urban

    2015-01-01

    Deregulated Notch signaling is linked to a variety of tumors and it is therefore important to learn more about the frequency and distribution of Notch mutations in a tumor context. In this report, we use data from the recently developed Cancer Cell Line Encyclopedia to assess the frequency and distribution of Notch mutations in a large panel of cancer cell lines in silico. Our results show that the mutation frequency of Notch receptor and ligand genes is at par with that for established oncogenes and higher than for a set of house-keeping genes. Mutations were found across all four Notch receptor genes, but with notable differences between protein domains, mutations were for example more prevalent in the regions encoding the LNR and PEST domains in the Notch intracellular domain. Furthermore, an in silico estimation of functional impact showed that deleterious mutations cluster to the ligand-binding and the intracellular domains of NOTCH1. For most cell line groups, the mutation frequency of Notch genes is higher than in associated primary tumors. Our results shed new light on the spectrum of Notch mutations after in vitro culturing of tumor cells. The higher mutation frequency in tumor cell lines indicates that Notch mutations are associated with a growth advantage in vitro, and thus may be considered to be driver mutations in a tumor cell line context. The online version of this article (doi:10.1186/s12885-015-1278-x) contains supplementary material, which is available to authorized users

  11. Design of UWB Filter with WLAN Notch

    Harish Kumar

    2012-01-01

    Full Text Available UWB technology- (operating in broad frequency range of 3.1–10.6 GHz based filter with WLAN notch has shown great achievement for high-speed wireless communications. To satisfy the UWB system requirements, a band pass filter with a broad pass band width, low insertion loss, and high stop-band suppression are needed. UWB filter with wireless local area network (WLAN notch at 5.6 GHz and 3 dB fractional bandwidth of 109.5% using a microstrip structure is presented. Initially a two-transmission-pole UWB band pass filter in the frequency range 3.1–10.6 GHz is achieved by designing a parallel-coupled microstrip line with defective ground plane structure using GML 1000 substrate with specifications: dielectric constant 3.2 and thickness 0.762 mm at centre frequency 6.85 GHz. In this structure a λ/4 open-circuited stub is introduced to achieve the notch at 5.6 GHz to avoid the interference with WLAN frequency which lies in the desired UWB band. The design structure was simulated on electromagnetic circuit simulation software and fabricated by microwave integrated circuit technique. The measured VNA results show the close agreement with simulated results.

  12. A Morphological Insight of the Femoral Vein

    Ferreira AH

    2015-10-01

    Full Text Available A total of 13 cadavers (12 men and 1 women of different age group were used for the study with the purpose to determine the prevalence of femoral vein duplication. Lower limb regions (26 sides were carefully dissected as per the standard dissection procedure. Femoral vein (unitruncular was found in 96.15% of specimen. Bitruncular configurations (total bifidity was found in a male cadaver of 75 years of age (3.85%. In the right lower limb, 6.5 cms below the inguinal ligament the femoral vein - lateral ramus received the lateral circumflex femoral vein, and the medial circumflex femoral vein, and the lateral and medial ramii formed a common venous trunk. Knowledge of the truncular venous variations is important to recognize and avoid potential errors in diagnosis of deep venous thrombosis of the femoral vein, in the case of an occluded duplicated trunk.

  13. Notch signaling inhibitor DAPT provides protection against acute craniocerebral injury.

    Hong-Mei Zhang

    Full Text Available Notch signaling pathway is involved in many physiological and pathological processes. The γ-secretase inhibitor DAPT inhibits Notch signaling pathway and promotes nerve regeneration after cerebral ischemia. However, neuroprotective effects of DAPT against acute craniocerebral injury remain unclear. In this study, we established rat model of acute craniocerebral injury, and found that with the increase of damage grade, the expression of Notch and downstream protein Hes1 and Hes5 expression gradually increased. After the administration of DAPT, the expression of Notch, Hes1 and Hes5 was inhibited, apoptosis and oxidative stress decreased, neurological function and cognitive function improved. These results suggest that Notch signaling can be used as an indicator to assess the severity of post-traumatic brain injury. Notch inhibitor DAPT can reduce oxidative stress and apoptosis after acute craniocerebral injury, and is a potential drug for the treatment of acute craniocerebral injury.

  14. Evaluation of perfusion of the femoral head after femoral neck fracture using bone scintigraphy

    Yamaguchi, Satoshi; Ishido, Yasuhiro [Saiseikai Sendai Hospital, Kagoshima (Japan); Okano, Toshihiro [Ibusuki National Hospital, Kagoshima (Japan); Komiya, Setsuro [Kagoshima Univ. (Japan). Faculty of Medicine

    2002-09-01

    We treated 13 patients for femoral neck fracture. They consisted of 2 males and 11 females, and were classified according to Garden stage classification; Stage I, 3 cases; Stage II, 2 cases; Stage III, 2 cases; Stage IV, 4 cases. Two trochanteric fracture cases were used by control. We evaluated perfusion of the femoral head after femoral neck fracture using bone scintigraphy, which is considered useful for evaluation of perfusion of the femoral neck before operation. (author)

  15. Evaluation of perfusion of the femoral head after femoral neck fracture using bone scintigraphy

    Yamaguchi, Satoshi; Ishido, Yasuhiro; Okano, Toshihiro; Komiya, Setsuro

    2002-01-01

    We treated 13 patients for femoral neck fracture. They consisted of 2 males and 11 females, and were classified according to Garden stage classification; Stage I, 3 cases; Stage II, 2 cases; Stage III, 2 cases; Stage IV, 4 cases. Two trochanteric fracture cases were used by control. We evaluated perfusion of the femoral head after femoral neck fracture using bone scintigraphy, which is considered useful for evaluation of perfusion of the femoral neck before operation. (author)

  16. Role of Notch Signaling in Human Breast Cancer Pathogenesis

    2006-11-01

    transform HMLE cells. Similarly, overexpression of ErbB2, a receptor tyrosine kinase upstream of Ras normally found overexpressed in many breast cancers ...Assess Notch-Ras cooperation in breast cancers in vivo: Since the major observation in this project has been the cooperation of Notch and Ras in HMLE ...metastasis. The in vitro cooperation between Notch and Ras in HMLE cells is mimicked in naturally arising breast cancers in vivo. Further dissection of the

  17. The Role of Notch Signaling Pathway in Breast Cancer Pathogenesis

    2005-07-01

    breast cancer cells, I tested whether ErbB2 overexpression will cooperate with Notch in HMLE cells. While overexpression of activated Notch1 failed to...tyrosine kinase upstream of Ras normally found overexpressed in many breast cancers , also failed to transform HMLE cells. These observations suggested...cooperation between Notch1IC and ErbB2 signaling in transforming HMLE cells. Breast cancers typically do not harbor oncogenic Ras mutations; nevertheless

  18. Estenose da fossa intercondilar após estabilização articular com retalho de fáscia lata em cães Intercondylar fossa stenosis after joint stabilization using a fascial strip in dogs

    André Luis Selmi

    2012-01-01

    Full Text Available Determinaram-se os índices de largura da fossa intercondilar (FI, após transecção do ligamento cruzado cranial em nove cães adultos submetidos à estabilização articular com retalho de fáscia lata. Os joelhos foram alocados em dois grupos, sendo o joelho direito (GI submetido à incisuroplastia troclear (ITR e posterior estabilização articular, e o joelho esquerdo submetido somente à substituição ligamentar (GC. Cada grupo foi dividido em três subgrupos correspondentes aos momentos de eutanásia aos 30, 90 e 180 dias de pós-operatório. Os índices de largura da FI foram determinados, macroscópica e radiograficamente, pela mensuração da abertura cranial da FI nos terços cranial, médio e caudal, e indexados em relação à largura epicondilar. Observou-se aumento significativo dos índices macroscópicos e radiográficos nas articulações do GI, sendo estes estatisticamente diferentes daqueles das articulações de GC. Não foi observada estenose intercondilar nos joelhos de GC após a estabilização articular. Conclui-se que a estabilização articular com retalho de fáscia lata preveniu a estenose da fossa intercondilar, e que a ITR promoveu o alargamento permanente dessa estrutura.Intercondylar fossa width indexes (IFWI were determined in nine adult dogs submitted to intercondylar notchplasty (IN after transection of the cranial cruciate ligament (CCL followed by a fascial strip stabilization. The right stifle was submitted to IN followed by fascial strip reconstruction of the CCL (GI while in the left stifle IN was not performed (GC. Each group was then divided into three subgroups which corresponded to time of euthanasia at 30, 90 and 180 days after surgery. IFWI were determined, both macroscopically and radiographically, by measuring the cranial outlet of the intercondylar fossa in relation to the epicondylar width. A significant increase was observed in indexes of GI following IN, and these differed from indexes of

  19. Analysis list: NOTCH1 [Chip-atlas[Archive

    Full Text Available NOTCH1 Blood + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/NOTCH1.1....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/NOTCH1.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/NOTC...H1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/NOTCH1.Blood.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Blood.gml ...

  20. The functional role of Notch signaling in human gliomas

    Stockhausen, Marie-Thérése; Kristoffersen, Karina; Poulsen, Hans Skovgaard

    2010-01-01

    have been referred to as brain cancer stem cells (bCSC), as they share similarities to normal neural stem cells in the brain. The Notch signaling pathway is involved in cell fate decisions throughout normal development and in stem cell proliferation and maintenance. The role of Notch in cancer is now...... firmly established, and recent data implicate a role for Notch signaling also in gliomas and bCSC. In this review, we explore the role of the Notch signaling pathway in gliomas with emphasis on its role in normal brain development and its interplay with pathways and processes that are characteristic...

  1. Progress Report on Alloy 617 Notched Specimen Testing

    McMurtrey, Michael David [Idaho National Lab. (INL), Idaho Falls, ID (United States); Wright, Richard Neil [Idaho National Lab. (INL), Idaho Falls, ID (United States); Lillo, Thomas Martin [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-08-01

    Creep behavior of Alloy 617 has been extensively characterized to support the development of a draft Code Case to qualify Alloy 617 in Section III division 5 of the ASME Boiler and Pressure Vessel Code. This will allow use of Alloy 617 in construction of nuclear reactor components at elevated temperatures and longer periods of time (up to 950°C and 100,000 hours). Prior to actual use, additional concerns not considered in the ASME code need to be addressed. Code Cases are based largely on uniaxial testing of smooth gage specimens. In service conditions, components will generally be under multi axial loading. There is also the concern of the behavior at discontinuities, such as threaded components. To address the concerns of multi axial creep behavior and at geometric discontinuities, notched specimens have been designed to create conditions representative of the states that service components experience. Two general notch geometries have been used for these series of tests: U notch and V notch specimens. The notches produce a tri axial stress state, though not uniform across the specimen. Characterization of the creep behavior of the U notch specimens and the creep rupture behavior of the V notch specimens provides a good approximation of the behavior expected of actual components. Preliminary testing and analysis have been completed and are reported in this document. This includes results from V notch specimens tested at 900°C and 800°C. Failure occurred in the smooth gage section of the specimen rather than at the root of the notch, though some damage was present at the root of the notch, where initial stress was highest. This indicates notch strengthening behavior in this material at these temperatures.

  2. Notch signaling and progenitor/ductular reaction in steatohepatitis.

    Carola M Morell

    Full Text Available Persistent hepatic progenitor cells (HPC activation resulting in ductular reaction (DR is responsible for pathologic liver repair in cholangiopathies. Also, HPC/DR expansion correlates with fibrosis in several chronic liver diseases, including steatohepatitis. Increasing evidence indicates Notch signaling as a key regulator of HPC/DR response in biliary and more in general liver injuries. Therefore, we aimed to investigate the role of Notch during HPC/DR activation in a mouse model of steatohepatitis.Steatohepatitis was generated using methionine-choline deficient (MCD diet. For hepatocyte lineage tracing, R26R-YFP mice were infected with AAV8-TBG-Cre.MCD diet promoted a strong HPC/DR response that progressively diffused in the lobule, and correlated with increased fibrosis and TGF-β1 expression. Notch signaling was unchanged in laser-capture microdissected HPC/DR, whereas Notch receptors were down regulated in hepatocytes. However, in-vivo lineage tracing experiments identified discrete hepatocytes showing Notch-1 activation and expressing (the Notch-dependent Sox9. Stimulation of AML-12 hepatocyte-cell line with immobilized Jag1 induced Sox9 and down-regulated albumin and BSEP expression. TGF-β1 treatment in primary hepatic stellate cells (HSC induced Jag1 expression. In MCD diet-fed mice, αSMA-positive HSC were localized around Sox9 expressing hepatocytes, suggesting that Notch activation in hepatocytes was promoted by TGF-β1 stimulated HSC. In-vivo Notch inhibition reduced HPC response and fibrosis progression.Our data suggest that Notch signaling is an important regulator of DR and that in steatohepatitis, hepatocytes exposed to Jag1-positive HSC, contribute to pathologic DR by undergoing Notch-mediated differentiation towards an HPC-like phenotype. Given the roles of Notch in fibrosis and liver cancer, these data suggest mesenchymal expression of Jag1 as an alternative therapeutic target.

  3. Precracking of round notched bars. Progress Report

    Scibetta, M.

    1996-02-01

    Precracking round notched bars is the first step before fracture mechanics testing. This report gives an overview of the different techniques described in the literature. Difficulties generally encountered are linked to the crack length determination and the creation of eccentric cracks. As the compliance technique is often used, a detailed study of the stress intensity factor and the compliance of the precracked bar under bending and tension is presented. Comparison with finite element calculations is made to validate the proposed analytical formulation. Finally a practical way for precracking is described

  4. Oncogenic Notch signaling in T-cell and B-cell lymphoproliferative disorders.

    Chiang, Mark Y; Radojcic, Vedran; Maillard, Ivan

    2016-07-01

    This article highlights recent discoveries about Notch activation and its oncogenic functions in lymphoid malignancies, and discusses the therapeutic potential of Notch inhibition. NOTCH mutations arise in a broad spectrum of lymphoid malignancies and are increasingly scrutinized as putative therapeutic targets. In T-cell acute lymphoblastic leukemia (T-ALL), NOTCH1 mutations affect the extracellular negative regulatory region and lead to constitutive Notch activation, although mutated receptors remain sensitive to Notch ligands. Other NOTCH1 mutations in T-ALL and NOTCH1/2 mutations in multiple B-cell malignancies truncate the C-terminal proline (P), glutamic acid (E), serine (S), threonine (T)-rich (PEST) domain, leading to decreased Notch degradation after ligand-mediated activation. Thus, targeting Notch ligand-receptor interactions could provide therapeutic benefits. In addition, we discuss recent reports on clinical testing of Notch inhibitors in T-ALL that influenced contemporary thinking on the challenges of targeting Notch in cancer. We review advances in the laboratory to address these challenges in regards to drug targets, the Notch-driven metabolome, and the sophisticated protein-protein interactions at Notch-dependent superenhancers that underlie oncogenic Notch functions. Notch signaling is a recurrent oncogenic pathway in multiple T- and B-cell lymphoproliferative disorders. Understanding the complexity and consequences of Notch activation is critical to define optimal therapeutic strategies targeting the Notch pathway.

  5. Notch sensitivity of ductile metallic foams : A computational study

    Mangipudi, K. R.; Onck, P. R.

    2011-01-01

    The role of notches in the fracture strength of metal foams has been studied using a multiscale model based on a two-dimensional Voronoi representation of the cellular architecture. The effect of the crack length to the specimen width ratio on the net section strength of double edge notch (DEN)

  6. Evaluation of Notch and Hypoxia Signaling Pathways in Chemically ...

    Hepatocellular carcinoma (HCC) is a common worldwide malignancy. Notch signaling pathway contributes to the genesis of diverse cancers, however, its role in HCC is unclear. Hypoxia is a common feature of HCC. Signal integration between Notch and hypoxia may be involved in HCC. The aim of this study was to ...

  7. Failure of a porous solid from a deep notch

    Redanz, Pia; Fleck, Norman A.; McMeeking, Robert M.

    1997-01-01

    A finite strain finite element method is used to examine the stress state near the tip of a deep notch in an elastic-plastic porous solid. The notch is loaded in mode I plane strain tension and small scale yielding is assumed. Two rate independent strain hardening material models are used...

  8. Common nonmutational NOTCH1 activation in chronic lymphocytic leukemia.

    Fabbri, Giulia; Holmes, Antony B; Viganotti, Mara; Scuoppo, Claudio; Belver, Laura; Herranz, Daniel; Yan, Xiao-Jie; Kieso, Yasmine; Rossi, Davide; Gaidano, Gianluca; Chiorazzi, Nicholas; Ferrando, Adolfo A; Dalla-Favera, Riccardo

    2017-04-04

    Activating mutations of NOTCH1 (a well-known oncogene in T-cell acute lymphoblastic leukemia) are present in ∼4-13% of chronic lymphocytic leukemia (CLL) cases, where they are associated with disease progression and chemorefractoriness. However, the specific role of NOTCH1 in leukemogenesis remains to be established. Here, we report that the active intracellular portion of NOTCH1 (ICN1) is detectable in ∼50% of peripheral blood CLL cases lacking gene mutations. We identify a "NOTCH1 gene-expression signature" in CLL cells, and show that this signature is significantly enriched in primary CLL cases expressing ICN1, independent of NOTCH1 mutation. NOTCH1 target genes include key regulators of B-cell proliferation, survival, and signal transduction. In particular, we show that NOTCH1 transactivates MYC via binding to B-cell-specific regulatory elements, thus implicating this oncogene in CLL development. These results significantly extend the role of NOTCH1 in CLL pathogenesis, and have direct implications for specific therapeutic targeting.

  9. Static and Fatigue Behavior Investigation of Artificial Notched Steel Reinforcement

    Yafei Ma

    2017-05-01

    Full Text Available Pitting corrosion is one of the most common forms of localized corrosion. Corrosion pit results in a stress concentration and fatigue cracks usually initiate and propagate from these corrosion pits. Aging structures may fracture when the fatigue crack reaches a critical size. This paper experimentally simulates the effects of pitting morphologies on the static and fatigue behavior of steel bars. Four artificial notch shapes are considered: radial ellipse, axial ellipse, triangle and length-variable triangle. Each shape notch includes six sizes to simulate a variety of pitting corrosion morphologies. The stress-strain curves of steel bars with different notch shape and depth are obtained based on static tensile testing, and the stress concentration coefficients for various conditions are determined. It was determined that the triangular notch has the highest stress concentration coefficient, followed by length-variable triangle, radial ellipse and axial ellipse shaped notches. Subsequently, the effects of notch depth and notch aspect ratios on the fatigue life under three stress levels are investigated by fatigue testing, and the equations for stress range-fatigue life-notch depth are obtained. Several conclusions are drawn based on the proposed study. The established relationships provide an experimental reference for evaluating the fatigue life of concrete bridges.

  10. Bone-femoral component interface gap after sagittal mechanical axis alignment is filled with new bone after cementless total knee arthroplasty.

    Kuriyama, Shinichi; Hyakuna, Katsufumi; Inoue, Satoshi; Kawai, Yasutsugu; Tamaki, Yasuyuki; Ito, Hiromu; Matsuda, Shuichi

    2018-05-01

    This study retrospectively evaluated the fate of mismatch between an uncemented femoral component and each femoral cut surface (i.e., wedge-shaped gap) relative to sagittal mechanical alignment in total knee arthroplasty (TKA). Primary TKA was performed on 99 consecutive knees. The femoral components were aligned to the sagittal mechanical axis with CT-based navigation. All patients were assessed with postoperative true lateral radiographs. Bone-side surfaces of the uncemented femoral component were divided into five zones: anterior flange, anterior chamfer, posterior chamfer, posterior part, and distal part, which were defined as zones 1 to 5, respectively. Bone filling of wedge-shaped gaps in each zone was evaluated after 1 year. Femoral anterior notching did not occur. However, wedge-shaped gaps were observed in at least one zone in 23 of 99 knees (23%), most frequently in zone 5 (18%). There were 9 and 7 gaps in zones 1 and 2, respectively. The femoral component showed malpositioning of approximately 3° of flexion in cases with wedge-shaped gaps in zones 2 and/or 5. After one year, 67% (6/9) of zone 1, 100% (7/7) of zone 2, and 94% (17/18) of zone 5 wedge-shaped gaps were filled in with new bone. Femoral alignment relative to sagittal mechanical axis caused wedge-shaped gaps due to unstable anterior bone cutting through hard bone, but the small gaps were not clinically significant and filled in within one year. Sagittal setting of the femoral component should aim for the anatomical axis rather than the mechanical axis. IV.

  11. Scalable Notch Antenna System for Multiport Applications

    Abdurrahim Toktas

    2016-01-01

    Full Text Available A novel and compact scalable antenna system is designed for multiport applications. The basic design is built on a square patch with an electrical size of 0.82λ0×0.82λ0 (at 2.4 GHz on a dielectric substrate. The design consists of four symmetrical and orthogonal triangular notches with circular feeding slots at the corners of the common patch. The 4-port antenna can be simply rearranged to 8-port and 12-port systems. The operating band of the system can be tuned by scaling (S the size of the system while fixing the thickness of the substrate. The antenna system with S: 1/1 in size of 103.5×103.5 mm2 operates at the frequency band of 2.3–3.0 GHz. By scaling the antenna with S: 1/2.3, a system of 45×45 mm2 is achieved, and thus the operating band is tuned to 4.7–6.1 GHz with the same scattering characteristic. A parametric study is also conducted to investigate the effects of changing the notch dimensions. The performance of the antenna is verified in terms of the antenna characteristics as well as diversity and multiplexing parameters. The antenna system can be tuned by scaling so that it is applicable to the multiport WLAN, WIMAX, and LTE devices with port upgradability.

  12. Treatment of neglected femoral neck fracture

    Anil K Jain

    2015-01-01

    Full Text Available Intra-capsular femoral neck fractures are seen commonly in elderly people following a low energy trauma. Femoral neck fracture has a devastating effect on the blood supply of the femoral head, which is directly proportional to the severity of trauma and displacement of the fracture. Various authors have described a wide array of options for treatment of neglected/nonunion (NU femoral neck fracture. There is lack of consensus in general, regarding the best option. This Instructional course article is an analysis of available treatment options used for neglected femoral neck fracture in the literature and attempt to suggest treatment guides for neglected femoral neck fracture. We conducted the "Pubmed" search with the keywords "NU femoral neck fracture and/or neglected femoral neck fracture, muscle-pedicle bone graft in femoral neck fracture, fibular graft in femoral neck fracture and valgus osteotomy in femoral neck fracture." A total of 203 print articles were obtained as the search result. Thirty three articles were included in the analysis and were categorized into four subgroups based on treatment options. (a treated by muscle-pedicle bone grafting (MPBG, (b closed/open reduction internal fixation and fibular grafting (c open reduction and internal fixation with valgus osteotomy, (d miscellaneous procedures. The data was pooled from all groups for mean neglect, the type of study (prospective or retrospective, classification used, procedure performed, mean followup available, outcome, complications, and reoperation if any. The outcome of neglected femoral neck fracture depends on the duration of neglect, as the changes occurring in the fracture area and fracture fragments decides the need and type of biological stimulus required for fracture union. In stage I and stage II (Sandhu′s staging neglected femoral neck fracture osteosynthesis with open reduction and bone grafting with MPBG or Valgus Osteotomy achieves fracture union in almost 90

  13. Gauging NOTCH1 Activation in Cancer Using Immunohistochemistry.

    Michael J Kluk

    Full Text Available Fixed, paraffin-embedded (FPE tissues are a potentially rich resource for studying the role of NOTCH1 in cancer and other pathologies, but tests that reliably detect activated NOTCH1 (NICD1 in FPE samples have been lacking. Here, we bridge this gap by developing an immunohistochemical (IHC stain that detects a neoepitope created by the proteolytic cleavage event that activates NOTCH1. Following validation using xenografted cancers and normal tissues with known patterns of NOTCH1 activation, we applied this test to tumors linked to dysregulated Notch signaling by mutational studies. As expected, frequent NICD1 staining was observed in T lymphoblastic leukemia/lymphoma, a tumor in which activating NOTCH1 mutations are common. However, when IHC was used to gauge NOTCH1 activation in other human cancers, several unexpected findings emerged. Among B cell tumors, NICD1 staining was much more frequent in chronic lymphocytic leukemia than would be predicted based on the frequency of NOTCH1 mutations, while mantle cell lymphoma and diffuse large B cell lymphoma showed no evidence of NOTCH1 activation. NICD1 was also detected in 38% of peripheral T cell lymphomas. Of interest, NICD1 staining in chronic lymphocytic leukemia cells and in angioimmunoblastic lymphoma was consistently more pronounced in lymph nodes than in surrounding soft tissues, implicating factors in the nodal microenvironment in NOTCH1 activation in these diseases. Among carcinomas, diffuse strong NICD1 staining was observed in 3.8% of cases of triple negative breast cancer (3 of 78 tumors, but was absent from 151 non-small cell lung carcinomas and 147 ovarian carcinomas. Frequent staining of normal endothelium was also observed; in line with this observation, strong NICD1 staining was also seen in 77% of angiosarcomas. These findings complement insights from genomic sequencing studies and suggest that IHC staining is a valuable experimental tool that may be useful in selection of

  14. Essential Role of Endothelial Notch1 in Angiogenesis

    Limbourg, Florian P.; Takeshita, Kyosuke; Radtke, Freddy; Bronson, Roderick T.; Chin, Michael T.; Liao, James K.

    2009-01-01

    Background Notch signaling influences binary cell fate decisions in a variety of tissues. The Notch1 receptor is widely expressed during embryogenesis and is essential for embryonic development. Loss of global Notch1 function results in early embryonic lethality, but the cell type responsible for this defect is not known. Here, we identify the endothelium as the primary target tissue affected by Notch1 signaling. Methods and Results We generated an endothelium-specific deletion of Notch1 using Tie2Cre and conditional Notch1flox/flox mice. Mutant embryos lacking endothelial Notch1 died at approximately embryonic day 10.5 with profound vascular defects in placenta, yolk sac, and embryo proper, whereas heterozygous deletion had no effect. In yolk sacs of mutant embryos, endothelial cells formed a primary vascular plexus indicative of intact vasculogenesis but failed to induce the secondary vascular remodeling required to form a mature network of well-organized large and small blood vessels, which demonstrates a defect in angiogenesis. These vascular defects were also evident in the placenta, where blood vessels failed to invade the placental labyrinth, and in the embryo proper, where defective blood vessel maturation led to pericardial and intersomitic hemorrhage. Enhanced activation of caspase-3 was detected in endothelial and neural cells of mutant mice, which resulted in enhanced apoptotic degeneration of somites and the neural tube. Conclusions These findings recapitulate the vascular phenotype of global Notch1-/- mutants and indicate an essential cell-autonomous role of Notch1 signaling in the endothelium during vascular development. These results may have important clinical implications with regard to Notch1 signaling in adult angiogenesis. PMID:15809373

  15. Subchondral insufficiency fractures of the femoral head

    Davies, M.; Cassar-Pullicino, V.N. [Department of Radiology, Robert Jones and Agnes Hunt Orthopaedic and District Hospital, Oswestry, SY10 7AG, Shropshire (United Kingdom); Darby, A.J. [Department of Pathology, Robert Jones and Agnes Hunt Orthopaedic and District Hospital, Oswestry, SY10 7AG, Shropshire (United Kingdom)

    2004-02-01

    The aim of this study was to increase awareness of, and to show the variable clinical and radiological features of, subchondral insufficiency fractures of the femoral head. The clinical and radiological findings in 7 patients with subchondral insufficiency fractures of the femoral head were reviewed retrospectively. The diagnosis was confirmed histologically in 4 patients. Radiographs were performed in all patients, MRI in 5 and scintigraphy in 4 patients. Radiographs showed varying degrees of femoral head collapse in 4 patients. In the remaining 3 patients radiographs showed a normal femoral head, regional osteoporosis and focal sclerosis, respectively. Magnetic resonance imaging showed a low-signal band on T1- and T2-weighted images in the subchondral bone adjacent or parallel to the articular surface associated with bone marrow oedema. Scintigraphy showed increased uptake in the femoral head. Insufficiency fractures of the femoral head are easily overlooked or confused with avascular necrosis and, when there is significant joint destruction, osteoarthritis. Unsuspected insufficiency fracture of the femoral head can lead to significant and rapid loss of bone stock in osteoporotic patients waiting for arthroplasty for osteoarthritis. Increased awareness of this condition will hopefully lead to earlier diagnosis and a successful outcome of conservative treatment. (orig.)

  16. Tyrosine phosphorylation and proteolytic cleavage of Notch are required for non-canonical Notch/Abl signaling in Drosophila axon guidance.

    Kannan, Ramakrishnan; Cox, Eric; Wang, Lei; Kuzina, Irina; Gu, Qun; Giniger, Edward

    2018-01-17

    Notch signaling is required for the development and physiology of nearly every tissue in metazoans. Much of Notch signaling is mediated by transcriptional regulation of downstream target genes, but Notch controls axon patterning in Drosophila by local modulation of Abl tyrosine kinase signaling, via direct interactions with the Abl co-factors Disabled and Trio. Here, we show that Notch-Abl axonal signaling requires both of the proteolytic cleavage events that initiate canonical Notch signaling. We further show that some Notch protein is tyrosine phosphorylated in Drosophila , that this form of the protein is selectively associated with Disabled and Trio, and that relevant tyrosines are essential for Notch-dependent axon patterning but not for canonical Notch-dependent regulation of cell fate. Based on these data, we propose a model for the molecular mechanism by which Notch controls Abl signaling in Drosophila axons. © 2018. Published by The Company of Biologists Ltd.

  17. Characterization of activating mutations of NOTCH3 in T-cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies.

    Bernasconi-Elias, P; Hu, T; Jenkins, D; Firestone, B; Gans, S; Kurth, E; Capodieci, P; Deplazes-Lauber, J; Petropoulos, K; Thiel, P; Ponsel, D; Hee Choi, S; LeMotte, P; London, A; Goetcshkes, M; Nolin, E; Jones, M D; Slocum, K; Kluk, M J; Weinstock, D M; Christodoulou, A; Weinberg, O; Jaehrling, J; Ettenberg, S A; Buckler, A; Blacklow, S C; Aster, J C; Fryer, C J

    2016-11-24

    Notch receptors have been implicated as oncogenic drivers in several cancers, the most notable example being NOTCH1 in T-cell acute lymphoblastic leukemia (T-ALL). To characterize the role of activated NOTCH3 in cancer, we generated an antibody that detects the neo-epitope created upon gamma-secretase cleavage of NOTCH3 to release its intracellular domain (ICD3), and sequenced the negative regulatory region (NRR) and PEST (proline, glutamate, serine, threonine) domain coding regions of NOTCH3 in a panel of cell lines. We also characterize NOTCH3 tumor-associated mutations that result in activation of signaling and report new inhibitory antibodies. We determined the structural basis for receptor inhibition by obtaining the first co-crystal structure of a NOTCH3 antibody with the NRR protein and defined two distinct epitopes for NRR antibodies. The antibodies exhibit potent anti-leukemic activity in cell lines and tumor xenografts harboring NOTCH3 activating mutations. Screening of primary T-ALL samples reveals that 2 of 40 tumors examined show active NOTCH3 signaling. We also identified evidence of NOTCH3 activation in 12 of 24 patient-derived orthotopic xenograft models, 2 of which exhibit activation of NOTCH3 without activation of NOTCH1. Our studies provide additional insights into NOTCH3 activation and offer a path forward for identification of cancers that are likely to respond to therapy with NOTCH3 selective inhibitory antibodies.

  18. Frequency of ipsilateral femoral neck fractures in patients with ...

    Background: Ipsilateral associated femoral neck and shaft fractures are reported to occur in 2.5-6% of all femoral shaft fractures. Objective: To establish the frequency of ipsilateral femoral neck fractures amongst all patients presenting with femoral shaft fractures in Mulago Hospital. Methodology: This was a descriptive ...

  19. Subtrochanteric femoral fracture during trochanteric nailing for the treatment of femoral shaft fracture.

    Yun, Ho Hyun; Oh, Chi Hun; Yi, Ju Won

    2013-09-01

    We report on three cases of subtrochanteric femoral fractures during trochanteric intramedullary nailing for the treatment of femoral shaft fractures. Trochanteric intramedullary nails, which have a proximal lateral bend, are specifically designed for trochanteric insertion. When combined with the modified insertion technique, trochanteric intramedullary nails reduce iatrogenic fracture comminution and varus malalignment. We herein describe technical aspects of trochanteric intramedullary nailing for femoral shaft fractures to improve its application and prevent implant-derived complications.

  20. Mandibular Ramus Notching As a Tool for Sexual Dimorphism

    Bibhuti Bhusana Panda

    2016-02-01

    Full Text Available Sex determination from a single or a part of bone is always difficult in absence of other bones of the same individual. The current study is an attempt to know the sex of an individual from the study of posterior ramus of mandible. The study was done from December, 2014 to August, 2015 in various Medical Colleges of the state of Odisha, India with the use of morbid anatomical specimen of mandibles and simple measuring instruments. The posterior ramus of adult mandibles were studied for presence or absence of any notching and if present its position in relation to occlusal plane. The study resulted, that there was a role of notch position in sex determination. The presence or absence of the notch though was not a consistent finding of all the mandibles. Males had frequent notching at the level of occlusal plane (P< 0.01 and females had frequent notching above the occlusal plane (P < 0.01. Notch present below the occlusal plane had no relation with sex. Accuracy of sexing mandible from the posterior ramus notch position was 61%, which was more for males (68.57% as compared to females (43.33%. So the posterior ramus of mandible could be considered for determination of sex of mandible but this should not be the sole criteria and should be correlated with the other standard criteria.

  1. On short cracks that depart from elastoplastic notch tips

    Verônica Miquelin Machado

    2017-07-01

    Full Text Available The behavior of short cracks that depart from elastoplastic notch tips is modeled to estimate the stresses required to initiate and to propagate cracks in notched structural components, and to evaluate the size of tolerable crack-like defects under general loading conditions. This analysis can model both fatigue and environmentally assisted cracking problems; can evaluate notch sensitivity in both cases; and can as well be used to establish design or acceptance criteria for tolerable non-propagating crack-like defects in such cases. The growth of short cracks is assumed driven by the applied stresses and by the stress gradient ahead the notch tip, and supported by the material resistances to crack initiation and to long crack propagation by fatigue or EAC. In the elastoplastic case, the stress gradient ahead of the notch tip is quantified by a J-field to consider the short crack behavior. The tolerable short crack predictions made by this model are evaluated by suitable fatigue and EAC tests of notched specimens specially designed to start nonpropagating cracks from the notch tips, both under elastic and elastoplastic conditions.

  2. Notch3 marks clonogenic mammary luminal progenitor cells in vivo.

    Lafkas, Daniel; Rodilla, Veronica; Huyghe, Mathilde; Mourao, Larissa; Kiaris, Hippokratis; Fre, Silvia

    2013-10-14

    The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive "triple negative" human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2(SAT) transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells.

  3. Observation of femoral and tibial insertion of the posterior cruciate ligament by using conventional CT and transparent 3D-CT

    Inoue, Masayuki; Tsukuda, Koichiro; Yasojima, Nobutoshi; Oota, Masahiro; Kasahara, Yasuhiko

    2011-01-01

    Presented are image data acquisitioned by the volume rendering (VR)-3D-CT and authors' transparent (T)-3D-CT to depict the bone contour, of medial intercondylar ridge (MIR) and posterior intercodylar fossa (PIF) at femoral and tibial insertion, respectively, of the posterior cruciate ligament (PCL) as those data are helpful for planning the reconstruction surgery of PCL and for confirming the femoral PCL insertion by using the C-arm during operation. Helical scanning is conducted with GE MD-CT (64DAS) to reconstruct VR-3D-CT image with the workstation ZIO's ZIO900M Quadra and T-3D-CT image, by reducing the opacity by pixel exclusion of the intraosseous lumen. MIR is observed in all 70 normal knees tested in VR-3D-CT and the bifurcate ridge, in 15 knees among them. In T-3D-CT image, distance data of the origin of MIR from Blumensaat's line and the angle of MIR and bone axis are calculated and presented. In VR-3D-CT and T-3D-CT images of PIF from 20 knees, actual measures of PIF slope angle (degree), PIF area ratio to joint surface (JS) (%), distance from JS to centers of anterolateral (AL) and posterolateral (PM) slopes (mm), and from medial and lateral JS to PIF posterior border (mm), and distance ratios of PM and AL to medial and lateral tibia, respectively, (%) are calculated and presented. Findings are: MIR originates at 45% distal point of Blumensaat's line; the articular line crosses with PIF at its center in T-3D-CT sagittal plane; centers of tibial AL and PM exist at the middle of frontal plane, and at 1.00 and 5.5 mm, respectively, distal points of JS of sagittal plane. The PIF data are rather comparable to those obtained in cadavers reported in 3 literatures and the present procedure is concluded to be valid. (author)

  4. High levels of Notch signaling down-regulate Numb and Numblike

    Chapman, G.; Liu, L.; Sahlgren, C.; Dahlqvist, C.; Lendahl, U.

    2006-01-01

    Inhibition of Notch signaling by Numb is critical for many cell fate decisions. In this study, we demonstrate a more complex relationship between Notch and the two vertebrate Numb homologues Numb and Numblike. Although Numb and Numblike at low levels of Notch signaling negatively regulated Notch,

  5. Herniography off femoral, obturator and perineal hernias

    Ekberg, O.; Nordblom, I.; Fork, F.T.; Gullmo, A.

    1985-01-01

    Positive contrast herniography was used in the workup of 550 patients with unclear groin pain. The majority of these patients had rather characteristic hernias of indirect, direct or femoral type. However, now and then diagnostic problems arose. A femoral hernia may look like a direct or even obturator hernia. There is also a variety of multilocular femoral hernias and other types. A femoral hernia may be present together with other hernias in the ipsilateral or contralateral groin. Obturator hernias are usually small but are always confined to the obturator canal laterally in the obturator foramen. Abnormalities in the pouch of Douglas may include a deep rectogenital pouch, diverticula and true herniations. These uncommon herniographic findings are described and discussed. (orig.) [de

  6. SEX DETERMINATION FROM FEMORAL HEAD DIAMETERS IN ...

    hi-tech

    2000-03-01

    Mar 1, 2000 ... In medico-legal cases where sophisticated methods of sex determination is lacking, these ... scientific methods(3). Using the visual method ... between the sexes and the values of the right and left femoral head diameters.

  7. Broadband notch filter design for millimeter-wave plasma diagnostics

    Furtula, Vedran; Michelsen, Poul; Leipold, Frank

    2010-01-01

    Notch filters are integrated in plasma diagnostic systems to protect millimeter-wave receivers from intensive stray radiation. Here we present a design of a notch filter with a center frequency of 140 GHz, a rejection bandwidth of ∼ 900 MHz, and a typical insertion loss below 2 dB in the passband...... of ±9 GHz. The design is based on a fundamental rectangular waveguide with eight cylindrical cavities coupled by T-junction apertures formed as thin slits. Parameters that affect the notch performance such as physical lengths and conductor materials are discussed. The excited resonance mode...

  8. Notch-1 mediates hypoxia-induced angiogenesis in rheumatoid arthritis.

    Gao, Wei; Sweeney, Catherine; Connolly, Mary; Kennedy, Aisling; Ng, Chin Teck; McCormick, Jennifer; Veale, Douglas J; Fearon, Ursula

    2012-07-01

    To examine the effect of hypoxia on Notch-1 signaling pathway components and angiogenesis in inflammatory arthritis. The expression and regulation of Notch-1, its ligand delta-like protein 4 (DLL-4) and downstream signaling components (hairy-related transcription factor 1 [HRT-1], HRT-2), and hypoxia-inducible factor 1α (HIF-1α) under normoxic and hypoxic conditions (1-3%) were assessed in synovial tissue specimens from patients with inflammatory arthritis and controls and in human dermal microvascular endothelial cells (HDMECs) by immunohistology, dual immunofluorescence staining (Notch-1/factor VIII), Western blotting, and real-time polymerase chain reaction. In vivo synovial tissue oxygen levels (tissue PO2) were measured under direct visualization at arthroscopy. HDMEC activation under hypoxic conditions in the presence of Notch-1 small interfering RNA (siRNA), the γ-secretase inhibitor DAPT, or dimethyloxalylglycine (DMOG) was assessed by Matrigel tube formation assay, migration assay, invasion assay, and matrix metalloproteinase 2 (MMP-2)/MMP-9 zymography. Expression of Notch-1, its ligand DLL-4, and HRT-1 was demonstrated in synovial tissue, with the strongest expression localized to perivascular/vascular regions. Localization of Notch-1 to synovial endothelium was confirmed by dual immunofluorescence staining. Notch-1 intracellular domain (NICD) expression was significantly higher in synovial tissue from patients with tissue PO2 of PO2 of >20 mm Hg (>3% O2). Exposure of HDMECs to 3% hypoxia induced HIF-1α and NICD protein expression and DLL-4, HRT-1, and HRT-2 messenger RNA expression. DMOG directly induced NICD expression, while Notch-1 siRNA inhibited hypoxia-induced HIF-1α expression, suggesting that Notch-1/HIF-1α signaling is bidirectional. Finally, 3% hypoxia-induced angiogenesis, endothelial cell migration, endothelial cell invasion, and proMMP-2 and proMMP-9 activities were inhibited by Notch-1 siRNA and/or the γ-secretase inhibitor DAPT. Our

  9. Bilateral femoral neck fractures following pelvic irradiation

    Mitsuda, Kenji; Nishi, Hosei; Oba, Hiroshi

    1977-01-01

    Over 300 cases of femoral neck fractures following radiotherapy for intrapelvic malignant tumor have been reported in various countries since Baensch reported this disease in 1927. In Japan, 40 cases or so have been reported, and cases of bilateral femoral neck fractures have not reached to ten cases. The authors experienced a case of 75 year-old female who received radiotherapy for cancer of the uterus, and suffered from right femoral neck fracture 3 months after and left femoral neck fracture one year and half after. As clinical symptoms, she had not previous history of trauma in bilateral femurs, but she complained of a pain in a hip joint and of gait disturbance. The pain in left femoral neck continued for about one month before fracture was recognized with roentgenogram. As histopathological findings, increase of fat marrow, decrease of bone trabeculae, and its marked degeneration were recognized. Proliferation of some blood vessels was found out, but thickness of the internal membrane and thrombogenesis were not recognized. Treatment should be performed according to degree of displacement of fractures. In this case, artificial joint replacement surgery was performed to the side of fracture of this time, because this case was bilateral femoral neck fractures and the patient had received artificial head replacement surgery in the other side of fracture formerly. (Tsunoda, M.)

  10. Notch signalling mediates reproductive constraint in the adult worker honeybee

    Duncan, Elizabeth J.; Hyink, Otto; Dearden, Peter K.

    2016-01-01

    The hallmark of eusociality is the reproductive division of labour, in which one female caste reproduces, while reproduction is constrained in the subordinate caste. In adult worker honeybees (Apis mellifera) reproductive constraint is conditional: in the absence of the queen and brood, adult worker honeybees activate their ovaries and lay haploid male eggs. Here, we demonstrate that chemical inhibition of Notch signalling can overcome the repressive effect of queen pheromone and promote ovary activity in adult worker honeybees. We show that Notch signalling acts on the earliest stages of oogenesis and that the removal of the queen corresponds with a loss of Notch protein in the germarium. We conclude that the ancient and pleiotropic Notch signalling pathway has been co-opted into constraining reproduction in worker honeybees and we provide the first molecular mechanism directly linking ovary activity in adult worker bees with the presence of the queen. PMID:27485026

  11. Complete Absence of Suprascapular Notch: A Case Report

    Rohini Mohan Pawar

    2015-10-01

    Full Text Available Suprascapular Nerve Entrapment (SSNE is an acquired neuropathy secondary to compression of suprascapular nerve in the Suprascapular Notch (SSN. Complete ossification of superior transverse scapular ligament may be a cause for suprascapular nerve entrapment. The absence of suprascapular notch is not very common condition, though its prevalence was quoted by Indian authors to be varying from 1.36% to 32.46% in different parts of the country. It is considered to be a predisposing factor for suprascapular nerve entrapment neuropathy. We noticed a male scapula without suprascapular notch in osteology section of Forensic Medicine department. In this case we observed costal and dorsal surfaces of the left scapula of a male without suprascapular notch at its superior border. The details of the said scapula are discussed in this report.

  12. Computer simulation of the Charpy V-notch toughness test

    Norris, D.M. Jr.

    1977-01-01

    The dynamic Charpy V-notch test was simulated on a computer. The calculational models (for A-533 Grade B class 1 steel) used both a rounded and a flat-tipped striker. The notch stress/strain state was found to be independent of the three-point loading type and was most strongly correlated with notch-opening displacement. The dynamic stress/strain state at the time of fracture initiation was obtained by comparing the calculated deformed shape with that obtained in interrupted Charpy V-notch tests where cracking had started. The calculation was also compared with stress/strain states calculated in other geometries at failure. The distribution and partition of specimen energy was calculated and adiabatic heating and strain rate are discussed

  13. A Compact Printed Quadruple Band-Notched UWB Antenna

    Xiaoyin Li

    2013-01-01

    Full Text Available A novel compact coplanar waveguide- (CPW- fed ultrawideband (UWB printed planar volcano-smoke antenna (PVSA with four band-notches for various wireless applications is proposed and demonstrated. The low-profile antenna consists of a C-shaped parasitic strip to generate a notched band at 8.01~8.55 GHz for the ITU band, two C-shaped slots, and an inverted U-shaped slot etched in the radiator patch to create three notched bands at 5.15~5.35 GHz, 5.75~5.85 GHz, and 7.25~7.75 GHz for filtering the WLAN and X-band satellite signals. Simulated and measured results both confirm that the proposed antenna has a broad bandwidth of 3.1~12 GHz with VSWR < 2 and good omnidirectional radiation patterns with four notched-bands.

  14. Dangerous Liaisons: Deviant Endothelium NOTCHes toward Tumor Metastasis.

    Guo, Peipei; Rafii, Shahin

    2017-03-13

    In this issue of Cancer Cell, Wieland et al. uncover a feedback loop in which tumor cells, by augmenting Notch signaling, provoke a senescent and pro-inflammatory state in endothelial cells, promoting neutrophil infiltration, tumor cell adhesion, and metastasis. Interfering with this Notch-dependent crosstalk may be a therapeutic approach to block metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Subtrochanteric Femoral Fracture during Trochanteric Nailing for the Treatment of Femoral Shaft Fracture

    Yun, Ho Hyun; Oh, Chi Hun; Yi, Ju Won

    2013-01-01

    We report on three cases of subtrochanteric femoral fractures during trochanteric intramedullary nailing for the treatment of femoral shaft fractures. Trochanteric intramedullary nails, which have a proximal lateral bend, are specifically designed for trochanteric insertion. When combined with the modified insertion technique, trochanteric intramedullary nails reduce iatrogenic fracture comminution and varus malalignment. We herein describe technical aspects of trochanteric intramedullary nai...

  16. Dll4-Notch signaling determines the formation of native arterial collateral networks and arterial function in mouse ischemia models.

    Cristofaro, Brunella; Shi, Yu; Faria, Marcella; Suchting, Steven; Leroyer, Aurelie S; Trindade, Alexandre; Duarte, Antonio; Zovein, Ann C; Iruela-Arispe, M Luisa; Nih, Lina R; Kubis, Nathalie; Henrion, Daniel; Loufrani, Laurent; Todiras, Mihail; Schleifenbaum, Johanna; Gollasch, Maik; Zhuang, Zhen W; Simons, Michael; Eichmann, Anne; le Noble, Ferdinand

    2013-04-01

    Arteriogenesis requires growth of pre-existing arteriolar collateral networks and determines clinical outcome in arterial occlusive diseases. Factors responsible for the development of arteriolar collateral networks are poorly understood. The Notch ligand Delta-like 4 (Dll4) promotes arterial differentiation and restricts vessel branching. We hypothesized that Dll4 may act as a genetic determinant of collateral arterial networks and functional recovery in stroke and hind limb ischemia models in mice. Genetic loss- and gain-of-function approaches in mice showed that Dll4-Notch signaling restricts pial collateral artery formation by modulating arterial branching morphogenesis during embryogenesis. Adult Dll4(+/-) mice showed increased pial collateral numbers, but stroke volume upon middle cerebral artery occlusion was not reduced compared with wild-type littermates. Likewise, Dll4(+/-) mice showed reduced blood flow conductance after femoral artery occlusion, and, despite markedly increased angiogenesis, tissue ischemia was more severe. In peripheral arteries, loss of Dll4 adversely affected excitation-contraction coupling in arterial smooth muscle in response to vasopressor agents and arterial vessel wall adaption in response to increases in blood flow, collectively contributing to reduced flow reserve. We conclude that Dll4-Notch signaling modulates native collateral formation by acting on vascular branching morphogenesis during embryogenesis. Dll4 furthermore affects tissue perfusion by acting on arterial function and structure. Loss of Dll4 stimulates collateral formation and angiogenesis, but in the context of ischemic diseases such beneficial effects are overruled by adverse functional changes, demonstrating that ischemic recovery is not solely determined by collateral number but rather by vessel functionality.

  17. Dll4-Notch signaling determines the formation of native arterial collateral networks and arterial function in mouse ischemia models

    Cristofaro, Brunella; Shi, Yu; Faria, Marcella; Suchting, Steven; Leroyer, Aurelie S.; Trindade, Alexandre; Duarte, Antonio; Zovein, Ann C.; Iruela-Arispe, M. Luisa; Nih, Lina R.; Kubis, Nathalie; Henrion, Daniel; Loufrani, Laurent; Todiras, Mihail; Schleifenbaum, Johanna; Gollasch, Maik; Zhuang, Zhen W.; Simons, Michael; Eichmann, Anne; le Noble, Ferdinand

    2013-01-01

    Arteriogenesis requires growth of pre-existing arteriolar collateral networks and determines clinical outcome in arterial occlusive diseases. Factors responsible for the development of arteriolar collateral networks are poorly understood. The Notch ligand Delta-like 4 (Dll4) promotes arterial differentiation and restricts vessel branching. We hypothesized that Dll4 may act as a genetic determinant of collateral arterial networks and functional recovery in stroke and hind limb ischemia models in mice. Genetic loss- and gain-of-function approaches in mice showed that Dll4-Notch signaling restricts pial collateral artery formation by modulating arterial branching morphogenesis during embryogenesis. Adult Dll4+/- mice showed increased pial collateral numbers, but stroke volume upon middle cerebral artery occlusion was not reduced compared with wild-type littermates. Likewise, Dll4+/- mice showed reduced blood flow conductance after femoral artery occlusion, and, despite markedly increased angiogenesis, tissue ischemia was more severe. In peripheral arteries, loss of Dll4 adversely affected excitation-contraction coupling in arterial smooth muscle in response to vasopressor agents and arterial vessel wall adaption in response to increases in blood flow, collectively contributing to reduced flow reserve. We conclude that Dll4-Notch signaling modulates native collateral formation by acting on vascular branching morphogenesis during embryogenesis. Dll4 furthermore affects tissue perfusion by acting on arterial function and structure. Loss of Dll4 stimulates collateral formation and angiogenesis, but in the context of ischemic diseases such beneficial effects are overruled by adverse functional changes, demonstrating that ischemic recovery is not solely determined by collateral number but rather by vessel functionality. PMID:23533173

  18. A three-dimensional analysis of the sigmoid notch

    Evan D. Collins

    2011-12-01

    Full Text Available Fractures of the distal radius are among the most common injuries of the upper extremity, though treatment has traditionally focused on restoration of the radiocarpal joint and late sequelae may persist. X-ray imaging underestimates sigmoid notch involvement following distal radius fractures. No classification system exists for disruption patterns of the sigmoid notch of the radius associated with distal radius fractures. This study quantifies the anatomy of the sigmoid notch and identifies the landmarks of the articular surface and proximal boundaries of the distal radioulnar joint (DRUJ capsule. Computed tomography scans of freshly frozen cadaveric hands were used - followed by dissection, and three-dimensional reconstruction of the distal radius and sigmoid notch. The sigmoid notch surface was divided into two surfaces and measured. The Anterior Posterior (AP and Proximal Distal (PD widths of the articulating surface were reviewed, along with the radius of curvature, version angle and depth. The study showed that the sigmoid notch is flatter than previously believed - and only the distal 69% of its surface is covered by cartilage. On average, it has about nine degrees of retroversion, and its average inclination is almost parallel to the anatomical axis of the radius. Clinical implications exist for evaluation of the DRUJ involvement in distal radius fractures or degenerative diseases and for future development and evaluation of hemiarthroplasty replacement of the distal radius.

  19. Notched K-wire for low thermal damage bone drilling.

    Liu, Yao; Belmont, Barry; Wang, Yiwen; Tai, Bruce; Holmes, James; Shih, Albert

    2017-07-01

    The Kirschner wire (K-wire) is a common bone drilling tool in orthopedic surgery to affix fractured bone. Significant heat is produced due to both the cutting and the friction between the K-wire and the bone debris during drilling. Such heat can result in high temperatures, leading to osteonecrosis and other secondary injuries. To reduce thermal injury and other high-temperature associated complications, a new K-wire design with three notches along the three-plane trocar tip fabricated using a thin micro-saw tool is studied. These notches evacuate bone debris and reduce the clogging and heat generation during bone drilling. A set of four K-wires, one without notches and three notched, with depths of 0.5, 0.75, and 1mm, are evaluated. Bone drilling experiments conducted on bovine cortical bone show that notched K-wires could effectively decrease the temperature, thrust force, and torque during bone drilling. K-wires with notches 1mm deep reduced the thrust force and torque by approximately 30%, reduced peak temperatures by 43%, and eliminated blackened burn marks in bone. This study demonstrates that a simple modification of the tip of K-wires can effectively reduce bone temperatures during drilling. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

  20. Effect of notch and alloying on steel properties during extension

    Vinokur, B.B.; Pilyushenko, U.L.; Kasatkin, O.G.

    1985-01-01

    A study was made on change of strength and plastic characteristics during extension of notched steel samples of 15 compositions containing often-used alloying elements in various amounts and combinations. The notch causes increase of strength and decrease of plastic properties of structural steels during extension. The most pronounced change of properties takes place for the notched sample with expansion angle close to 180 deg. Reduction of notch expansion angle below 150 deg causes slower decrease of the rate of property change. Nickel alloying and vanadium, titanium microalloying assist the improvement of steel plasticity despite the increase of strength properties. Introduction of these elements in steel compensate partially for the negative notch effect. Alloying by silicon, molybdenum and tungsten results in steel strengthening and chromium alloying causes some loss of strength. Manse, chromium, silicon, molybdenum and tungsten cause decrease of plasticity, which intensifies the negative notch effect. When determining concentration ranges of carbon and alloying elements within the limits of quality composition it is necessary to consider both technology and possibility of sufficient change of properties especially in the case of stress concentrator presence in structures

  1. Femoral component rotation in patellofemoral joint replacement.

    van Jonbergen, Hans-Peter W; Westerbeek, Robin E

    2018-06-01

    Clinical outcomes in patellofemoral joint replacement may be related to femoral component rotation. Assessment of rotational alignment is however difficult as patients with isolated patellofemoral osteoarthritis often have trochlear dysplasia. The use of the medial malleolus as a landmark to guide rotation has been suggested. The purpose of our study was to evaluate this technique with regard to femoral component rotation, and to correlate rotation with clinical outcomes at one-year follow-up. Forty-one knees in 39 patients had patellofemoral joint replacement using the Zimmer Gender-Solutions patellofemoral prosthesis. Intraoperatively, we determined femoral component rotational alignment using an extramedullary rod aimed at the inferior tip of the medial malleolus. Postoperatively, we measured the angle between the femoral component and the anatomical transepicondylar axis using CT. The amount of rotation was correlated with clinical outcomes at one-year follow-up. Forty knees in 38 patients were available for one-year follow-up. Mean femoral component rotation relative to the anatomical transepicondylar axis was 1.4° external rotation (range, -3.8 to 5.7°). We found no statistically significant correlation between femoral component rotation and change from baseline KOOS subscales at one-year follow-up. Our findings show that when using the medial malleolus as a landmark to guide rotation, the femoral component of the patellofemoral prosthesis was oriented in external rotation relative to the anatomical transepicondylar axis in 80% of knees. Our study did not show a relation between the amount of external rotation and clinical outcomes. Level III. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Femoral rotation unpredictably affects radiographic anatomical lateral distal femoral angle measurements

    Miles, James Edward

    2016-01-01

    Objective: To describe the effects of internal and external femoral rotation on radiographic measurements of the anatomical lateral distal femoral angle (a-LDFA) using two methods for defining the anatomical proximal femoral axis (a-PFA). Methods: Digital radiographs were obtained of 14 right...... femora at five degree intervals from 10° external rotation to 10° internal rotation. Using freely available software, a-LDFA measurements were made using two different a-PFA by a single observer on one occasion. Results: Mean a-LDFA was significantly greater at 10° external rotation than at any other...... rotation. The response of individual femora to rotation was unpredictable, although fairly stable within ±5° of zero rotation. Mean a-LDFA for the two a-PFA methods differed by 1.5°, but were otherwise similarly affected by femoral rotation. Clinical significance: If zero femoral elevation can be achieved...

  3. Evaluation of a pig femoral head osteonecrosis model

    Kim Harry

    2010-03-01

    Full Text Available Abstract Background A major cause of osteonecrosis of the femoral head is interruption of a blood supply to the proximal femur. In order to evaluate blood circulation and pathogenetic alterations, a pig femoral head osteonecrosis model was examined to address whether ligature of the femoral neck (vasculature deprivation induces a reduction of blood circulation in the femoral head, and whether transphyseal vessels exist for communications between the epiphysis and the metaphysis. We also tested the hypothesis that the vessels surrounding the femoral neck and the ligamentum teres represent the primary source of blood flow to the femoral head. Methods Avascular osteonecrosis of the femoral head was induced in Yorkshire pigs by transecting the ligamentum teres and placing two ligatures around the femoral neck. After heparinized saline infusion and microfil perfusion via the abdominal aorta, blood circulation in the femoral head was evaluated by optical and CT imaging. Results An angiogram of the microfil casted sample allowed identification of the major blood vessels to the proximal femur including the iliac, common femoral, superficial femoral, deep femoral and circumflex arteries. Optical imaging in the femoral neck showed that a microfil stained vessel network was visible in control sections but less noticeable in necrotic sections. CT images showed a lack of microfil staining in the epiphysis. Furthermore, no transphyseal vessels were observed to link the epiphysis to the metaphysis. Conclusion Optical and CT imaging analyses revealed that in this present pig model the ligatures around the femoral neck were the primary cause of induction of avascular osteonecrosis. Since the vessels surrounding the femoral neck are comprised of the branches of the medial and the lateral femoral circumflex vessels, together with the extracapsular arterial ring and the lateral epiphyseal arteries, augmentation of blood circulation in those arteries will improve

  4. Comparison of femoral morphology and bone mineral density between femoral neck fractures and trochanteric fractures.

    Maeda, Yuki; Sugano, Nobuhiko; Saito, Masanobu; Yonenobu, Kazuo

    2011-03-01

    Many studies that analyzed bone mineral density (BMD) and skeletal factors of hip fractures were based on uncalibrated radiographs or dual-energy xray absorptiometry (DXA). Spatial accuracy in measuring BMD and morphologic features of the femur with DXA is limited. This study investigated differences in BMD and morphologic features of the femur between two types of hip fractures using quantitative computed tomography (QCT). Forty patients with hip fractures with normal contralateral hips were selected for this study between 2003 and 2007 (trochanteric fracture, n=18; femoral neck fracture, n=22). Each patient underwent QCT of the bilateral femora using a calibration phantom. Using images of the intact contralateral femur, BMD measurements were made at the point of minimum femoral-neck cross-sectional area, middle of the intertrochanteric region, and center of the femoral head. QCT images also were used to measure morphologic features of the hip, including hip axis length, femoral neck axis length, neck-shaft angle, neck width, head offset, anteversion of the femoral neck, and cortical index at the femoral isthmus. No significant differences were found in trabecular BMD between groups in those three regions. Patients with trochanteric fractures showed a smaller neck shaft angle and smaller cortical index at the femoral canal isthmus compared with patients with femoral neck fractures. We conclude that severe osteoporosis with thinner cortical bone of the femoral diaphysis is seen more often in patients with trochanteric fracture than in patients with femoral neck fracture. Level IV, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

  5. Correlation of ultrasound appearance, gross anatomy, and histology of the femoral nerve at the femoral triangle.

    Lonchena, Tiffany K; McFadden, Kathryn; Orebaugh, Steven L

    2016-01-01

    Correlation between ultrasound appearance, gross anatomic characteristics, and histologic structure of the femoral nerve (FN) is lacking. Utilizing cadavers, we sought to characterize the anatomy of the FN, and provide a quantitative measure of its branching. We hypothesize that at the femoral crease, the FN exists as a group of nerve branches, rather than a single nerve structure, and secondarily, that this transition into many branches is apparent on ultrasonography. Nineteen preserved cadavers were investigated. Ultrasonography was sufficient to evaluate the femoral nerve in nine specimens; gross dissection was utilized in all 19. Anatomic characteristics were recorded, including distances from the inguinal ligament to femoral crease, first nerve branch, and complete arborization of the nerve. The nerves from nine specimens were excised for histologic analysis. On ultrasound, the nerve became more flattened, widened, and less discrete as it coursed distally. Branching of the nerve was apparent in 12 of 18 images, with mean distance from inguinal ligament of 3.9 (1.0) cm. However, upon dissection, major branching of the femoral nerve occurred at 3.1 (1.0) cm distal to the inguinal ligament, well proximal to the femoral crease. Histologic analysis was consistent with findings at dissection. The femoral nerve arborizes into multiple branches between the inguinal ligament and the femoral crease. Initial branching is often high in the femoral triangle. As hypothesized, the FN exists as a closely associated group of nerve branches at the level of the femoral crease; however, the termination of the nerve into multiple branches is not consistently apparent on ultrasonography.

  6. Void coalescence and fracture behavior of notched and un-notched tensile tested specimens in fine grain dual phase steel

    Saeidi, N., E-mail: navidsae@gmail.com [Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Ashrafizadeh, F.; Niroumand, B. [Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Forouzan, M.R.; Mohseni mofidi, S. [Department of Mechanical Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Barlat, F. [Materials Mechanics Laboratory (MML), Graduate Institute of Ferrous Technology (GIFT), Pohang University of Science and Technology POSTECH, San 31 Hyoja-dong, Nam-gu, Pohang, Gyeongbuk 790-784 (Korea, Republic of)

    2015-09-17

    Due to growing global concern about the environmental issues, steel developers have been forced by automobile makers to produce more efficient steel grades with high strength to weight ratios along with high crashworthiness performance. In order to find deficiencies of the existing steels and develop superior steel products, detailed understanding of deformation and damage behavior in the existing steels is needed. In the present research, deformation and damage evolution during room temperature uniaxial tensile test of a modern high strength Dual Phase Steel, i.e. DP780, were studied. Detailed scanning electron microscopy (SEM) examination of the microstructures of notched and un-notched tensile fractured specimens revealed that in notched specimen, plastic deformation was concentrated more within the notched region. Therefore, much higher reduction in thickness with a high reduction gradient occurred in this region, In the un-notched specimen, however, plastic deformation was more uniformly distributed in larger parts of the gauge length, and therefore, thickness reduction happened with a lower gradient. Although geometric notch on the specimen did not change the void nucleation and growth mechanisms, the kinetics of these phenomena was influenced. On the other hand, voids linkage mechanism tended to change from void coalescence in the un-notched specimen to void sheeting in the notched specimen. Moreover, three different models developed by Brown & Embury (BM), Thomason and Pardoen were employed to predict the final fracture strain. It was revealed that, BM model showed much more accurate predictions for the studied DP steel in comparison with those of Thomason and Pardoens’ models.

  7. Void coalescence and fracture behavior of notched and un-notched tensile tested specimens in fine grain dual phase steel

    Saeidi, N.; Ashrafizadeh, F.; Niroumand, B.; Forouzan, M.R.; Mohseni mofidi, S.; Barlat, F.

    2015-01-01

    Due to growing global concern about the environmental issues, steel developers have been forced by automobile makers to produce more efficient steel grades with high strength to weight ratios along with high crashworthiness performance. In order to find deficiencies of the existing steels and develop superior steel products, detailed understanding of deformation and damage behavior in the existing steels is needed. In the present research, deformation and damage evolution during room temperature uniaxial tensile test of a modern high strength Dual Phase Steel, i.e. DP780, were studied. Detailed scanning electron microscopy (SEM) examination of the microstructures of notched and un-notched tensile fractured specimens revealed that in notched specimen, plastic deformation was concentrated more within the notched region. Therefore, much higher reduction in thickness with a high reduction gradient occurred in this region, In the un-notched specimen, however, plastic deformation was more uniformly distributed in larger parts of the gauge length, and therefore, thickness reduction happened with a lower gradient. Although geometric notch on the specimen did not change the void nucleation and growth mechanisms, the kinetics of these phenomena was influenced. On the other hand, voids linkage mechanism tended to change from void coalescence in the un-notched specimen to void sheeting in the notched specimen. Moreover, three different models developed by Brown & Embury (BM), Thomason and Pardoen were employed to predict the final fracture strain. It was revealed that, BM model showed much more accurate predictions for the studied DP steel in comparison with those of Thomason and Pardoens’ models

  8. Trastuzumab Resistance: Role for Notch Signaling

    Kinnari Mehta

    2009-01-01

    Full Text Available Epidermal growth factor receptor-2 (ErbB-2/HER2 is a potent breast oncogene that has been shown to be amplified in 20% of breast cancers. Overexpression of ErbB-2 predicts for aggressive tumor behavior, resistance to some cytotoxic and antihormonal therapies, and poor overall survival. Trastuzumab, the humanized, monoclonal antibody directed against ErbB-2 has shown tremendous efficacy and improved overall survival for women when combined with a taxane-based chemotherapy. However, resistance to trastuzumab remains a major concern, most notably in women with metastatic breast cancer. Numerous mechanisms that include overexpression of alternate receptor tyrosine kinases and/or loss of critical tumor suppressors have been proposed in the last several years to elucidate trastuzumab resistance. Here we review the many possible mechanisms of action that could contribute to resistance, and novel therapies to prevent or reverse the resistant phenotype. Moreover, we provide a critical role for Notch signaling cross-talk with overlapping or new signaling networks in trastuzumab-resistant breast.

  9. Heterogeneity of breast cancer stem cells as evidenced with Notch-dependent and Notch-independent populations

    Wong, Nelson K Y; Fuller, Megan; Sung, Sandy; Wong, Fred; Karsan, Aly

    2012-01-01

    Studies have suggested the potential importance of Notch signaling to the cancer stem cell population in some tumors, but it is not known whether all cells in the cancer stem cell fraction require Notch activity. To address this issue, we blocked Notch activity in MCF-7 cells by expressing a dominant-negative MAML-GFP (dnMAML) construct, which inhibits signaling through all Notch receptors, and quantified the effect on tumor-initiating activity. Inhibition of Notch signaling reduced primary tumor sphere formation and side population. Functional quantification of tumor-initiating cell numbers in vivo showed a significant decrease, but not a complete abrogation, of these cells in dnMAML-expressing cells. Interestingly, when assessed in secondary assays in vitro or in vivo, there was no difference in tumor-initiating activity between the dnMAML-expressing cells and control cells. The fact that a subpopulation of dnMAML-expressing cells was capable of forming primary and secondary tumors indicates that there are Notch-independent tumor-initiating cells in the breast cancer cell line MCF-7. Our findings thus provide direct evidence for a heterogeneous cancer stem cell pool, which will require combination therapies against multiple oncogenic pathways to eliminate the tumor-initiating cell population

  10. Femoral head vitality after intracapsular hip fracture

    Stroemqvist, B.

    1983-01-01

    Femoral head vitality before, during and at various intervals from the operation was determined by tetracycline labeling and/or 99 sp (m)Tc-MDP scintimetry. In a three-year follow-up, healing prognosis could be determined by scintimetry 3 weeks from operation; deficient femoral head vitality predicting healing complications and retained vitality predicting uncomplicated healing. A comparison between pre- and postoperative scintimetry indicated that further impairment of the femoral head vitality could be caused by the operative procedure, and as tetracycline labeling prior to and after fracture reduction in 370 fractures proved equivalent, it was concluded that the procedure of osteosynthesis probably was responsible for capsular vessel injury, using a four-flanged nail. The four-flanged nail was compared with a low-traumatic method of osteosynthesis, two hook-pins, in a prospective randomized 14 month study, and the postoperative femoral head vitality was significantly better in the hook-pin group. This was also clearly demonstrated in a one-year follow-up for the fractures included in the study. Parallel to these investigations, the reliability of the methods of vitality determination was found satisfactory in methodologic studies. For clinical purpose, primary atraumatic osteosynthesis, postoperative prognostic scintimetry and early secondary arthroplasty when indicated, was concluded to be the appropriate approach to femoral neck fracture treatment. (Author)

  11. Avascular necrosis of the femoral head

    Kokubo, Takeshi; Takatori, Yoshio; Kamogawa, Morihide; Nakamura, Toshitaka; Ninomiya, Setsuo; Yoshikawa, Kohki; Itai, Yuji; Iio, Masahiro; Mitamura, Tadayuki

    1990-01-01

    T1-weighted MR images of thirty-six hips in 25 patients with avascular necrosis of the femoral head were obtained two to five times during the course of 2 to 26 months. We investigated these MR images in the light of the chronological change and compared them with plain radiographs. MR images changes in 16 femoral head; in general, the abnormal low intensity area in the femoral head reduced in extent and the internal high intensity area became smaller of disappeared. Thirteen femoral heads among them became more flattened on plain radiographs in the same period. It is noted that four different zones are defined in the femoral head after bone necrosis takes place: the dead bone marrow, the dead marrow which still contains fat, the reactive interface and the hyperemic bone marrow. In T1-weighted MR images, the dead bone marrow, the reactive interface and the hyperemic bone marrow are demonstrated as low intensity area, while the dead marrow containing fat may remain high in intensity. On the basis of this knowledge of histopathology and MR images of this disease, we suggest that reduction of the abnormal low intensity area and disappearance of the internal high intensity area on MR images can be regarded as diminution of hyperemia in the living bone marrow and loss of fat in the dead bone marrow, respectively. (author)

  12. Notched audiograms and noise exposure history in older adults.

    Nondahl, David M; Shi, Xiaoyu; Cruickshanks, Karen J; Dalton, Dayna S; Tweed, Ted S; Wiley, Terry L; Carmichael, Lakeesha L

    2009-12-01

    Using data from a population-based cohort study, we compared four published algorithms for identifying notched audiograms and compared their resulting classifications with noise exposure history. Four algorithms: (1) , (2) , (3) , and (4) were used to identify notched audiograms. Audiometric evaluations were collected as a part of the 10-yr follow-up examinations of the Epidemiology of Hearing Loss Study, in Beaver Dam, WI (2003-2005, N = 2395). Detailed noise exposure histories were collected by interview at the baseline examination (1993-1995) and updated at subsequent visits. An extensive history of occupational noise exposure, participation in noisy hobbies, and firearm usage was used to evaluate consistency of the notch classifications with the history of noise exposure. The prevalence of notched audiograms varied greatly by definition (31.7, 25.9, 47.2, and 11.7% for methods 1, 2, 3, and 4, respectively). In this cohort, a history of noise exposure was common (56.2% for occupational noise, 71.7% for noisy hobbies, 13.4% for firearms, and 81.2% for any of these three sources). Among participants with a notched audiogram, almost one-third did not have a history of occupational noise exposure (31.4, 33.0, 32.5, and 28.1% for methods 1, 2, 3, and 4, respectively), and approximately 11% did not have a history of exposure to any of the three sources of noise (11.5, 13.6, 10.3, and 7.6%). Discordance was greater in women than in men. These results suggest that there is a poor agreement across existing algorithms for audiometric notches. In addition, notches can occur in the absence of a positive noise history. In the absence of an objective consensus definition of a notched audiogram and in light of the degree of discordance in women between noise history and notches by each of these algorithms, researchers should be cautious about classifying noise-induced hearing loss by notched audiograms.

  13. NOTCH2 signaling confers immature morphology and aggressiveness in human hepatocellular carcinoma cells.

    Hayashi, Yoshihiro; Osanai, Makoto; Lee, Gang-Hong

    2015-10-01

    The NOTCH family of membranous receptors plays key roles during development and carcinogenesis. Since NOTCH2, yet not NOTCH1 has been shown essential for murine hepatogenesis, NOTCH2 rather than NOTCH1 may be more relevant to human hepatocarcinogenesis; however, no previous studies have supported this hypothesis. We therefore assessed the role of NOTCH2 in human hepatocellular carcinoma (HCC) by immunohistochemistry and cell culture. Immunohistochemically, 19% of primary HCCs showed nuclear staining for NOTCH2, indicating activated NOTCH2 signaling. NOTCH2-positive HCCs were on average in more advanced clinical stages, and exhibited more immature cellular morphology, i.e. higher nuclear-cytoplasmic ratios and nuclear densities. Such features were not evident in NOTCH1‑positive HCCs. In human HCC cell lines, abundant NOTCH2 expression was associated with anaplasia, represented by loss of E-cadherin. When NOTCH2 signaling was stably downregulated in HLF cells, an anaplastic HCC cell line, the cells were attenuated in potential for in vitro invasiveness and migration, as well as in vivo tumorigenicity accompanied by histological maturation. Generally, inverse results were obtained for a differentiated HCC cell line, Huh7, manipulated to overexpress activated NOTCH2. These findings suggested that the NOTCH2 signaling may confer aggressive behavior and immature morphology in human HCC cells.

  14. Cell-Cell Contact Area Affects Notch Signaling and Notch-Dependent Patterning.

    Shaya, Oren; Binshtok, Udi; Hersch, Micha; Rivkin, Dmitri; Weinreb, Sheila; Amir-Zilberstein, Liat; Khamaisi, Bassma; Oppenheim, Olya; Desai, Ravi A; Goodyear, Richard J; Richardson, Guy P; Chen, Christopher S; Sprinzak, David

    2017-03-13

    During development, cells undergo dramatic changes in their morphology. By affecting contact geometry, these morphological changes could influence cellular communication. However, it has remained unclear whether and how signaling depends on contact geometry. This question is particularly relevant for Notch signaling, which coordinates neighboring cell fates through direct cell-cell signaling. Using micropatterning with a receptor trans-endocytosis assay, we show that signaling between pairs of cells correlates with their contact area. This relationship extends across contact diameters ranging from micrometers to tens of micrometers. Mathematical modeling predicts that dependence of signaling on contact area can bias cellular differentiation in Notch-mediated lateral inhibition processes, such that smaller cells are more likely to differentiate into signal-producing cells. Consistent with this prediction, analysis of developing chick inner ear revealed that ligand-producing hair cell precursors have smaller apical footprints than non-hair cells. Together, these results highlight the influence of cell morphology on fate determination processes. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Selective arteriography in femoral head fractures

    Mannella, P; Galeotti, R; Borrelli, M; Benea, G; Massari, L; Chiarelli, G M

    1986-01-01

    The choice between conservative and radical operation in case of femoral neck fractures is very important because it is the determining factor for a successfull therapy. In case of epiphysial necrosis, an endoprosthesis as well as an osteosynthesis will be carried out. Selective arteriography of the medical circumflex artery represents the most reliable study to establish, immediately after the fractures, the possible presence of a post-traumatic ischemic necrosis. Angiography, as a reliable diagnostic tool, has to be carried out in the most selective way and needs the image subtraction technique. The authors report their preliminary results on the reliability of angiography in the femoral epiphyseal ischemic necrosis diagnosed by comparing the results of angiography with the wood light test carried out on the surgically removed femoral head. 18 refs.

  16. 99mTc-MDP scintigraphy of femoral head necrosis following femoral neck fracture

    Lee, Soon Jin; Lee, Jun Hyung; Kim, Eun Kyung; Lee, Sun Wha; Kim, Soon Yong

    1985-01-01

    Secondary ischemic necrosis of femoral head due to loss of blood supply following to femoral neck fracture is well known. The regional distribution of bone-seeking radiopharmaceuricals in the skeleton can depend on a number of factors, but bone blood flow is a major physiological determinant of regional skeletal uptake of Tc-99m polyphosphate and bone imaging may thus be used for the evaluation of vascularity of the femoral head. The authors made a comparative study of scintigraphic findings and operative findings of 28 cases of femoral neck fracture treated at Kyung Hee University Hospital from April 1980 to May 1984. The results were as follows: 1. In 16 cases of proven avascular necorsis of femoral head, scintigraphy showed absent or decreased activity in 14 cases (87.5%), while radiography showed increased density in 10 cases (62.5%). 2. In 12 cases of proven vital femoral head, scintigraphy showed increased activity in 9 cases (75%) and radiography showed decreased density in 9 cases (75%). 3. 99mTc-MDP scintigraphy was an excellent and useful method for assessing bone vitality of femoral head

  17. {sup 99m}Tc-MDP scintigraphy of femoral head necrosis following femoral neck fracture

    Lee, Soon Jin; Lee, Jun Hyung; Kim, Eun Kyung; Lee, Sun Wha; Kim, Soon Yong [Kyung Hee University School of Medicine, Seoul (Korea, Republic of)

    1985-02-15

    Secondary ischemic necrosis of femoral head due to loss of blood supply following to femoral neck fracture is well known. The regional distribution of bone-seeking radiopharmaceuricals in the skeleton can depend on a number of factors, but bone blood flow is a major physiological determinant of regional skeletal uptake of Tc-99m polyphosphate and bone imaging may thus be used for the evaluation of vascularity of the femoral head. The authors made a comparative study of scintigraphic findings and operative findings of 28 cases of femoral neck fracture treated at Kyung Hee University Hospital from April 1980 to May 1984. The results were as follows: 1. In 16 cases of proven avascular necorsis of femoral head, scintigraphy showed absent or decreased activity in 14 cases (87.5%), while radiography showed increased density in 10 cases (62.5%). 2. In 12 cases of proven vital femoral head, scintigraphy showed increased activity in 9 cases (75%) and radiography showed decreased density in 9 cases (75%). 3. 99mTc-MDP scintigraphy was an excellent and useful method for assessing bone vitality of femoral head.

  18. The effect of residual stresses induced by prestraining on fatigue life of notched specimens

    Sadeler, R.; Ozel, A.; Kaymaz, I.; Totik, Y.

    2005-06-01

    The effect of tensile prestraining-induced residual stress on the fatigue life of notched steel parts was investigated. The study was performed on AISI 4140 steel. Rotating bending fatigue tests were carried out on semicircular notched specimens with different notch radii in the as-quenched and tempered conditions. Metallography of the specimens was performed by means of light optical microscopy. The finite-element method was used to evaluate the residual stress distribution near the notch region. Fatigue tests revealed fatigue life improvement for notched specimens, which changes depending on the notch radii and applied stress. Scanning electron microscopy was used to examine the fracture surfaces of the specimens.

  19. frequency of ipsilateral femoral neck fractures in patients

    Background: Ipsilateral associated femoral neck and shaft fractures are reported to occur in 2.5-6% of all femoral shaft ... nailing of the shaft fracture, which makes treatment of the neck ... chest, spine), while the other had maxillofacial injuries.

  20. Femoral component loosening after hip resurfacing arthroplasty

    Zustin, Jozef; Sauter, Guido; Hahn, Michael; Morlock, Michael M.; Ruether, Wolfgang; Amling, Michael

    2010-01-01

    Before the re-introduction of the current generation of total hip resurfacing arthroplasty, component loosening and osteolysis were of great concern to the orthopaedic community. Early, mid- and long-term clinical results are encouraging, but component loosening still exists. Macroscopic, contact radiographic and histopathological analyses after undecalcified preparation of bone tissue specimens were performed. To investigate the frequency and morphological patterns of the loosening of the femoral component, we analysed a series of 190 retrieved femoral remnants that were revised for aseptic failures. Thirty-five (18.4%) hips were revised for clinical and/or radiographic loosening of the femoral component. Pseudoarthrosis (n = 17; median in situ time: 16 weeks, interquartile range [IQR]: 9 to 34), collapsed osteonecrosis (n = 5; median in situ time: 79 weeks, IQR: 63 to 97), cement-socket debonding (n = 3; median in situ time: 89 weeks, IQR: 54 to 97) and at later follow-up bone-cement loosening (n = 10; median in situ time: 175 weeks; IQR 112 to 198; p =0.005) were distinct patterns of the femoral remnant-implant loosening. Fibrocartilaginous metaplasia of interface bone trabeculae (n = 38; median in situ time: 61 weeks, IQR: 32 to 138) was strongly associated with femoral component loosening (p = 0.009). Both the trabecular hyperosteoidosis (n = 32; median in situ time: 71 weeks, IQR 50 to 129) and excessive intraosseous lymphocyte infiltration (n = 12; median in situ time: 75 weeks, IQR 51 to 98) at the bone-cement interface correlated strongly with fibrocartilaginous metaplasia (p = 0.001 and p = 0.016 respectively) and all three lesions were associated with the female gender (p = 0.021, p = 0.009, and p = 0.051). Femoral component loosening at early follow-up was mostly caused by pathological changes of the femoral remnant bone tissue: pseudoarthrosis and collapsed osteonecrosis. Fibrocartilaginous metaplasia was frequently observed in hips with femoral

  1. Excessive Anteversion Leads to Failure at 3 Years Due to Impingement as Evidenced by Twin Notches in Ti6A4V Stem

    Thomas Donaldson

    2015-08-01

    Full Text Available A 63-year old female with bilateral hip replacements was referred to our clinic for pain and elevated metal ions. Her left hip had been revised earlier. The right hip had an SROM Ti6Al4V stem implanted with a 28mm head, a 28mm CoCr liner and Pinnacle Ti6Al4V shell. The patient reported pain, numbness, tingling, and repeated clicking and popping sensations with gait. She specifically noted that her hip would freeze while walking and could pop rising from a chair. Repeated metal ion levels showed Co (blood17ppb, Cr (serum 21ppb, and Ti (blood at 69ppb. CT-images of right hip revealed femoral stem anteversion was 43° and cup anteversion was 40°, for a combined anteversion of 83°. The right hip was revised 3.5 years postoperatively for persistent pain and elevated metal ions. At surgery, large twin notches were evident on her posterior femoral neck and 10mm-wide scalloped damage was evident in the rim of the Ti6A4V shell. SEM-imaging revealed contaminating layers on CoCr head containing elements Al, V and Ti. These indicated that titanium-alloy particles liberated by cup-to-neck impingements had transferred to the CoCr bearings. Our intent in this case was not to document that a MOM bearing produced impingement damage, because this case clearly implicated adverse surgical positioning. Rather, the intent was to document sequelae likely in a THA case that has a metal cup impinging on a metal femoral neck. In particular, twin notches on the femoral neck indicated that this patient was routinely impinging her Ti6Al4V shell against the Ti6Al4V neck and also subluxing her femoral head out of the cup. These signs are a clear indication that one or both components must be revised, as opposed to simply replacing the CoCr liner with a revision polyethylene liner.

  2. Coastal dune dynamics in response to excavated foredune notches

    Ruessink, B. G.; Arens, S. M.; Kuipers, M.; Donker, J. J. A.

    2018-04-01

    Dune management along developed coasts has traditionally focussed on the suppression of the geomorphic dynamics of the foredune to improve its role in sea defence. Because a stabilized foredune acts as an almost total barrier to aeolian transport from the beach, the habitat diversity in the more landward dunes has degraded. With the overarching objective to mitigate this undesirable loss in biodiversity, dune management projects nowadays increasingly intend to restore aeolian dynamics by reconnecting the beach-dune system with notches excavated through the foredune. Here, we use repeat topographic survey data to examine the geomorphic response of a coastal dune system in the Dutch National Park Zuid-Kennemerland to five notches excavated in 2012-2013 within an 850-m stretch of the 20-m high established foredune. The notches were dug in a V-shape (viewed onshore), with a width between approximately 50 and 100 m at the top, a (cross-dune) length between 100 and 200 m, and excavation depths between 9 and 12.5 m. The 1 × 1 m digital terrain models, acquired with airborne Lidar and UAV photogrammetry, illustrate that during the 3-year survey period the notches developed into a U-shape because of wall deflation, and that up to 8-m thick and 150-m long depositional lobes formed landward of the notches. Sand budget computations showed that the sand volume of the entire study area increased by about 22,750 m3/year, which, given the 850-m width of the study area, corresponds to an aeolian input from the beach of approximately 26.5 m3/m/year. Between 2006 and 2012 all wind-blown beach sand deposited on the seaward side of the foredune; since 2013, the notches have caused 75% of the sand to be deposited landward of the foredune. This highlights that the notches are highly effective conduits for aeolian transport into the back dunes. Future monitoring is required to determine for how long the notches will stimulate aeolian dynamics and if (and when) vegetation eventually

  3. Why does necking ignore notches in dynamic tension?

    Rotbaum Y.

    2015-01-01

    Full Text Available Recent experimental work has revealed that necking of tensile specimens, subjected to dynamic loading, is a deterministic phenomenon, governed by the applied boundary conditions. Furthermore it was shown that the potential sited, dictated by the boundary conditions, may prevail even in the presence of a notch, thus necking may occur away of the notched region. The present paper combines experimental and numerical work to address this issue. Specifically, it is shown that the dynamic tensile failure locus is dictated by both the applied velocity boundary condition and the material mechanical properties, specifically strain-rate sensitivity and strain-rate hardening. It is shown that at sufficiently high impact velocities, the flows stress in the notch vicinity becomes quite higher than in the rest of the specimen, so that while the former resists deformation, it transfers the load to the latter, resulting in the formation of a local neck and failure away from the notch. Small local perturbations in the material properties are shown to be sufficient to stabilize the structure under local failure until a neck forms elsewhere. While the physical observations are quite counterintuitive with respect to the engineering views of stress concentrator's effect, the present work rationalizes those observations and also provides information for the designers of dynamically tensioned structures that may contain notches or similar flaws.

  4. Notch pathway signaling in the skin antagonizes Merkel cell development.

    Logan, Gregory J; Wright, Margaret C; Kubicki, Adam C; Maricich, Stephen M

    2018-02-15

    Merkel cells are mechanosensitive skin cells derived from the epidermal lineage whose development requires expression of the basic helix-loop-helix transcription factor Atoh1. The genes and pathways involved in regulating Merkel cell development during embryogenesis are poorly understood. Notch pathway signaling antagonizes Atoh1 expression in many developing body regions, so we hypothesized that Notch signaling might inhibit Merkel cell development. We found that conditional, constitutive overexpression of the Notch intracellular domain (NICD) in mouse epidermis significantly decreased Merkel cell numbers in whisker follicles and touch domes of hairy skin. Conversely, conditional deletion of the obligate NICD binding partner RBPj in the epidermis significantly increased Merkel cell numbers in whisker follicles, led to the development of ectopic Merkel cells outside of touch domes in hairy skin epidermis, and altered the distribution of Merkel cells in touch domes. Deletion of the downstream Notch effector gene Hes1 also significantly increased Merkel cell numbers in whisker follicles. Together, these data demonstrate that Notch signaling regulates Merkel cell production and patterning. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Oncogenic programmes and Notch activity: an 'organized crime'?

    Dominguez, Maria

    2014-04-01

    The inappropriate Notch signalling can influence virtually all aspect of cancer, including tumour-cell growth, survival, apoptosis, angiogenesis, invasion and metastasis, although it does not do this alone. Hence, elucidating the partners of Notch that are active in cancer is now the focus of much intense research activity. The genetic toolkits available, coupled to the small size and short life of the fruit fly Drosophila melanogaster, makes this an inexpensive and effective animal model, suited to large-scale cancer gene discovery studies. The fly eye is not only a non-vital organ but its stereotyped size and disposition also means it is easy to screen for mutations that cause tumours and metastases and provides ample opportunities to test cancer theories and to unravel unanticipated nexus between Notch and other cancer genes, or to discover unforeseen Notch's partners in cancer. These studies suggest that Notch's oncogenic capacity is brought about not simply by increasing signal strength but through partnerships, whereby oncogenes gain more by cooperating than acting individually, as in a ring 'organized crime'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Genetic screens to identify new Notch pathway mutants in Drosophila.

    Giagtzoglou, Nikolaos

    2014-01-01

    Notch signaling controls a wide range of developmental processes, including proliferation, apoptosis, and cell fate specification during both development and adult tissue homeostasis. The functional versatility of the Notch signaling pathway is tightly linked with the complexity of its regulation in different cellular contexts. To unravel the complexity of Notch signaling, it is important to identify the different components of the Notch signaling pathway. A powerful strategy to accomplish this task is based on genetic screens. Given that the developmental context of signaling is important, these screens should be customized to specific cell populations or tissues. Here, I describe how to perform F1 clonal forward genetic screens in Drosophila to identify novel components of the Notch signaling pathway. These screens combine a classical EMS (ethyl methanesulfonate) chemical mutagenesis protocol along with clonal analysis via FRT-mediated mitotic recombination. These F1 clonal screens allow rapid phenotypic screening within clones of mutant cells induced at specific developmental stages and in tissues of interest, bypassing the pleiotropic effects of isolated mutations. More importantly, since EMS mutations have been notoriously difficult to map to specific genes in the past, I briefly discuss mapping methods that allow rapid identification of the causative mutations.

  7. Identification of epidermal Pdx1 expression discloses different roles of Notch1 and Notch2 in murine Kras(G12D-induced skin carcinogenesis in vivo.

    Pawel K Mazur

    Full Text Available BACKGROUND: The Ras and Notch signaling pathways are frequently activated during development to control many diverse cellular processes and are often dysregulated during tumorigenesis. To study the role of Notch and oncogenic Kras signaling in a progenitor cell population, Pdx1-Cre mice were utilized to generate conditional oncogenic Kras(G12D mice with ablation of Notch1 and/or Notch2. METHODOLOGY/PRINCIPAL FINDINGS: Surprisingly, mice with activated Kras(G12D and Notch1 but not Notch2 ablation developed skin papillomas progressing to squamous cell carcinoma providing evidence for Pdx1 expression in the skin. Immunostaining and lineage tracing experiments indicate that PDX1 is present predominantly in the suprabasal layers of the epidermis and rarely in the basal layer. Further analysis of keratinocytes in vitro revealed differentiation-dependent expression of PDX1 in terminally differentiated keratinocytes. PDX1 expression was also increased during wound healing. Further analysis revealed that loss of Notch1 but not Notch2 is critical for skin tumor development. Reasons for this include distinct Notch expression with Notch1 in all layers and Notch2 in the suprabasal layer as well as distinctive p21 and β-catenin signaling inhibition capabilities. CONCLUSIONS/SIGNIFICANCE: Our results provide strong evidence for epidermal expression of Pdx1 as of yet not identified function. In addition, this finding may be relevant for research using Pdx1-Cre transgenic strains. Additionally, our study confirms distinctive expression and functions of Notch1 and Notch2 in the skin supporting the importance of careful dissection of the contribution of individual Notch receptors.

  8. Acoustic emission during tensile deformation and fracture of nuclear grade AISI type 304 stainless steel specimens with notches

    Mukhopadhyay, C.K.; Jayakumar, T.; Baldev Raj

    1996-01-01

    Acoustic emission generated during tensile deformation and fracture of nuclear grade AISI type 304 stainless steel specimens with notches has been studied. The extent of acoustic activity generated depends on notch tip severity, notch tip blunting and tearing of the notches. The equation N=AK m applied to the acoustic emission data of the notched specimens has shown good correlation. Acoustic emission technique can be used to estimate the size of an unknown notch. (author)

  9. Angiographic analysis of avascular necrosis of a femoral head -selective angiography of medial femoral circumflex artery-

    Ryu, Kyung Nam; Yoon, Yup; Lee, Sun Wha; Lim, Jae Hoon [Kyung Hee University Hospital, Seoul (Korea, Republic of)

    1991-07-15

    The degree of anatomical revascularization of a necrotic femoral head and traumatic hip would provide information about treatment and prognosis. The authors analyzed the vascular changes of femoral head among unilateral avascular necrosis, bilateral avascular necrosis, and traumatic hips. Forty - four patients with avascular necrosis and 19 patients with traumatic hips were examined by selective angiography of the medial femoral circumflex artery. In the traumatic hip cases, 12 (63%) showed occlusion, 2 (11%) hypertrophy of the capsular branches, and 5 ( 26 % ) were normal . In the avascular necrosis cases, 15 (25%) showed occlusion, 39 (67%) had hypertrophy of the capsular branches, and 4 (7%) had normal findings. Hypertrophy of the superior capsular branch of the medial femoral circumflex artery is more frequently observed in avascular necrosis than in traumatic hip. Bilateral avascular necrosis reveals more frequent incidences than unilateral cases. Selective angiography could help in the therapy plan and also provide information about the contralateral side.

  10. Angiographic analysis of avascular necrosis of a femoral head -selective angiography of medial femoral circumflex artery-

    Ryu, Kyung Nam; Yoon, Yup; Lee, Sun Wha; Lim, Jae Hoon

    1991-01-01

    The degree of anatomical revascularization of a necrotic femoral head and traumatic hip would provide information about treatment and prognosis. The authors analyzed the vascular changes of femoral head among unilateral avascular necrosis, bilateral avascular necrosis, and traumatic hips. Forty - four patients with avascular necrosis and 19 patients with traumatic hips were examined by selective angiography of the medial femoral circumflex artery. In the traumatic hip cases, 12 (63%) showed occlusion, 2 (11%) hypertrophy of the capsular branches, and 5 ( 26 % ) were normal . In the avascular necrosis cases, 15 (25%) showed occlusion, 39 (67%) had hypertrophy of the capsular branches, and 4 (7%) had normal findings. Hypertrophy of the superior capsular branch of the medial femoral circumflex artery is more frequently observed in avascular necrosis than in traumatic hip. Bilateral avascular necrosis reveals more frequent incidences than unilateral cases. Selective angiography could help in the therapy plan and also provide information about the contralateral side

  11. Fibrous dysplasia of the femoral neck

    Savage, P.E.; Stoker, D.J.

    1984-01-01

    Fibrous dysplasia of the femur is usually observed in the intertrochanteric region. It is rarely confined to the femoral neck. We present four cases illustrating the radiographic appearance and spectrum of this condition which all showed the relatively lucent variety of fibrous dysplasia with varying degrees of expansion and surrounding sclerosis. The natural history of this condition is discussed. (orig.)

  12. Femoral Hernia At Mulago Hospital, Uganda

    user

    2004-12-02

    Dec 2, 2004 ... consecutive patients operated for femoral hernia over a period of twelve months. Results: There were ... The age ranged from 42 years to 70 years old with a mean of 54.6 years old. All the .... cholecystectomy. At this point in ...

  13. Radiation-induced femoral head necrosis

    2011-03-25

    Mar 25, 2011 ... had open medial menisectomy of the left knee following medial meniscal tear ... postoperative recovery and mobilised full weight-bearing immediately [Figure 6]. ... obtained from the oncologists at the time of this review), and there was a ... previous trauma such as femoral neck fracture, Gaucher's disease ...

  14. Transvenous liver biopsy via the femoral vein

    Khosa, F.; McNulty, J.G.; Hickey, N.; O'Brien, P.; Tobin, A.; Noonan, N.; Ryan, B.; Keeling, P.W.N.; Kelleher, D.P.; McDonald, G.S.A.

    2003-01-01

    AIM: To study the safety, effectiveness and diagnostic value of transvenous forceps biopsy of the liver in 54 patients with coagulopathy, gross ascites or morbid obesity and suspected liver disease in whom percutaneous liver biopsy was contraindicated. MATERIAL AND METHODS: Forceps biopsy of the liver via the femoral vein was attempted in 54 adult patients with advanced liver disease of unknown aetiology who had coagulation disorders (41 cases), gross ascites (11 cases) or morbid obesity (two cases). In each patient two to six biopsies (average four) were taken using a radial jaw forceps inserted via the right or left femoral vein. RESULTS: The procedure was successful in 53 cases. Hepatic vein catheterization failed in one patient. Adequate liver tissue for diagnosis was obtained in 84% of cases. One patient developed delayed haemorrhage at 12 h from a capsular leak that was undetected during the biopsy procedure. This patient required blood transfusions and laparotomy to control bleeding. There were no deaths in the 53 patients studied. Transient minor chest and shoulder pain was encountered during sheath insertion into a hepatic vein in 23 patients. Three patients developed a femoral vein haematoma, which resolved with conservative treatment. CONCLUSION: Transvenous liver biopsy via the femoral vein is another safe, effective, simple alternative technique of biopsy when the percutaneous route is contraindicated

  15. Postmortem Femoral Blood Concentrations of Risperidone

    Linnet, Kristian; Johansen, Sys Stybe

    2014-01-01

    Postmortem femoral blood concentrations of the antipsychotic drug risperidone and the active metabolite 9-hydroxyrisperidone were determined by an achiral LC-MS/MS method in 38 cases. The cause of death was classified as unrelated to risperidone in 30 cases, in which the sum of the concentration ...

  16. Femoral Prosthesis Infection by Rhodotorula mucilaginosa▿

    Savini, Vincenzo; Sozio, Federica; Catavitello, Chiara; Talia, Marzia; Manna, Assunta; Febbo, Fabio; Balbinot, Andrea; Di Bonaventura, Giovanni; Piccolomini, Raffaele; Parruti, Giustino; D'Antonio, Domenico

    2008-01-01

    This case report is a case history of a femoral prosthesis infection caused by Rhodotorula mucilaginosa in a human immunodeficiency virus patient. Though the pathogenicity of this organism for bone tissue has been previously reported, this is the first reported case of an orthopedic prosthesis infection by this species of the genus Rhodotorula. PMID:18753353

  17. Aseptic necrosis of femoral head complicating thalassemia

    Orzincolo, C.; Castaldi, G.; Scutellary, P.N.; Bariani, L.; Pinca, A.

    1986-01-01

    Aseptic necrosis of the femoral head is described in 4 patients, selected from 280 patients with homozygous β-thalassemia (Cooley anemia). The incidence of the complication appears to be very high (14.5per mille) in thalassemia, compared to the general population. The possible mechanism are discussed. (orig.)

  18. Lateral femoral traction pin entry: risk to the femoral artery and other medial neurovascular structures

    Appleton Paul

    2010-01-01

    Full Text Available Abstract Background Femoral skeletal traction assists in the reduction and transient stabilization of pelvic, acetabular, hip, and femoral fractures when splinting is ineffective. Traditional teaching has recommended a medial entry site for insertion of the traction pin in order to minimize injury to the femoral artery as it passes through Hunter's canal. The present anatomical study evaluates the risk to the femoral artery and other medial neurovascular structures using a lateral entry approach. Methods Six embalmed cadavers (twelve femurs were obtained for dissection. Steinman pins were drilled from lateral to medial at the level of the superior pole of the patella, at 2 cm, and at 4 cm proximal to this point. Medial superficial dissection was then performed to identify the saphenous nerve, the superior medial geniculate artery, the adductor hiatus, the tendinous insertion of the adductor magnus and the femoral artery. Measurements localizing these anatomic structures relative to the pins were obtained. Results The femoral artery was relatively safe and was no closer than 29.6 mm (mean from any of the three Steinman pins. The superior medial geniculate artery was the medial structure at most risk. Conclusions Lateral femoral traction pin entry is a safe procedure with minimal risk to the saphenous nerve and femoral artery. Of the structures examined, only the superior medial geniculate artery is at a risk of iatrogenic injury due to its position. The incidence of such injury in clinical practice and its clinical significance is not known. Lateral insertion facilitates traction pin placement since it minimizes the need to move the contralateral extremity out of the way of the drilling equipment or the need to elevate or externally rotate the injured extremity relative to the contralateral extremity.

  19. Digital notch filter based active damping for LCL filters

    Yao, Wenli; Yang, Yongheng; Zhang, Xiaobin

    2015-01-01

    . In contrast, the active damping does not require any dissipation elements, and thus has become of increasing interest. As a result, a vast of active damping solutions have been reported, among which multi-loop control systems and additional sensors are necessary, leading to increased cost and complexity....... In this paper, a notch filter based active damping without the requirement of additional sensors is proposed, where the inverter current is employed as the feedback variable. Firstly, a design method of the notch filter for active damping is presented. The entire system stability has then been investigated...... in the z-domain. Simulations and experiments are carried out to verify the proposed active damping method. Both results have confirmed that the notch filter based active damping can ensure the entire system stability in the case of resonances with a good system performance....

  20. Passive notch circuit for pulsed-off compression fields

    Nunnally, W.C.

    1976-06-01

    The operation and simulated results of a passive notch circuit used to pulse off the field in a multiturn, fusion-power system, compression coil are presented. The notch circuit permits initial plasma preparation at field zero, adiabatic compression as the field returns to its initial value, and long field decay time for plasma confinement. The major advantages and disadvantages of the notch circuit are compared with those of a standard capacitor power supply system. The major advantages are that: (1) slow-rising fields can be used for adiabatic compression, (2) solid-state switches can be used because of the inherent current and voltage waveforms, and (3) long field decay times are easier to attain than with single-turn coils

  1. Planar Ultrawideband Antenna with Photonically Controlled Notched Bands

    Drasko Draskovic

    2013-01-01

    Full Text Available A design of a planar microstrip-fed ultrawideband (UWB printed circular monopole antenna with optically controlled notched bands is presented. The proposed antenna is composed of a circular ultrawideband patch, with an etched T-shaped slot controlled by an integrated silicon switch. The slot modifies the frequency response of the antenna suppressing 3.5–5 GHz band when the switch is in open state. The optical switch is controlled by a low-power near-infrared (808 nm laser diode, which causes the change in the frequency response of the antenna generating a frequency notch. This solution could be expanded to include several notches in the antenna frequency response achieving a fully reconfigurable UWB antenna. The antenna could be remotely controlled at large distances using optical fiber. The prototype antenna has been fully characterized to verify these design concepts.

  2. NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells

    Mauro Di Ianni

    2018-04-01

    Full Text Available To investigate chronic lymphocytic leukemia (CLL-initiating cells, we assessed NOTCH1 mutation/expression in hematopoietic stem cells (HSCs. In NOTCH1-mutated CLL, we detected subclonal mutations in 57% CD34+/CD38− HSCs. NOTCH1 mutation was present in 66% CD34+/CD38+ progenitor cells displaying an increased mutational burden compared to HSCs. Flow cytometric analysis revealed significantly higher NOTCH1 activation in CD34+/CD38− and CD34+/CD38+ cells from CLL patients, regardless NOTCH1 mutation compared to healthy donors. Activated NOTCH1 resulted in overexpression of the NOTCH1 target c-MYC. We conclude that activated NOTCH1 is an early event in CLL that may contribute to aberrant HSCs in this disease.

  3. NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells.

    Di Ianni, Mauro; Baldoni, Stefano; Del Papa, Beatrice; Aureli, Patrizia; Dorillo, Erica; De Falco, Filomena; Albi, Elisa; Varasano, Emanuela; Di Tommaso, Ambra; Giancola, Raffaella; Accorsi, Patrizia; Rotta, Gianluca; Rompietti, Chiara; Silva Barcelos, Estevão Carlos; Campese, Antonio Francesco; Di Bartolomeo, Paolo; Screpanti, Isabella; Rosati, Emanuela; Falzetti, Franca; Sportoletti, Paolo

    2018-01-01

    To investigate chronic lymphocytic leukemia (CLL)-initiating cells, we assessed NOTCH1 mutation/expression in hematopoietic stem cells (HSCs). In NOTCH1- mutated CLL, we detected subclonal mutations in 57% CD34+/CD38- HSCs. NOTCH1 mutation was present in 66% CD34+/CD38+ progenitor cells displaying an increased mutational burden compared to HSCs. Flow cytometric analysis revealed significantly higher NOTCH1 activation in CD34+/CD38- and CD34+/CD38+ cells from CLL patients, regardless NOTCH1 mutation compared to healthy donors. Activated NOTCH1 resulted in overexpression of the NOTCH1 target c-MYC. We conclude that activated NOTCH1 is an early event in CLL that may contribute to aberrant HSCs in this disease.

  4. Damage Study in Notched Particulate Composie Specimens Under Nonuniform Strain Loading

    Kwon, Y

    1999-01-01

    .... The numerical specimen considered had a semi-circular notch with a linearly varying length. The initial crack size occurring at the notch tip was modeled and predicted using a micro/macro-approach along with a damage model...

  5. Notch signalling in primary cutaneous CD30+ lymphoproliferative disorders: a new therapeutic approach?

    Kamstrup, M R; Biskup, E; Gniadecki, R

    2010-01-01

    The oncogenic potential of deregulated Notch signalling has been described in several haematopoietic malignancies. We have previously reported an increased expression of Notch1 in primary cutaneous CD30+ lymphoproliferative disorders, lymphomatoid papulosis and primary cutaneous anaplastic large...

  6. Role of Notch signalling pathway in cancer and its association with ...

    The Notch signalling pathway is an evolutionarily conserved cell signalling pathway involved in the development of organ- ... Abnormal Notch signalling is seen in many cancers like T-cell acute ...... Morgan T. H. 1917 The theory of the gene.

  7. Notch3 is dispensable for thymocyte β-selection and Notch1-induced T cell leukemogenesis.

    Sara Suliman

    Full Text Available Notch1 (N1 signaling induced by intrathymic Delta-like (DL ligands is required for T cell lineage commitment as well as self-renewal during "β-selection" of TCRβ⁺CD4⁻CD8⁻ double negative 3 (DN3 T cell progenitors. However, over-expression of the N1 intracellular domain (ICN1 renders N1 activation ligand-independent and drives leukemic transformation during β-selection. DN3 progenitors also express Notch3 (N3 mRNA, and over-expression of ligand-independent mutant N3 (ICN3 influences β-selection and drives T cell leukemogenesis. However, the importance of ligand-activated N3 in promoting β-selection and ICN1-induced T cell leukemogenesis has not been examined. To address these questions we generated mice lacking functional N3. We confirmed that DN3 progenitors express N3 protein using a N3-specific antibody. Surprisingly however, N3-deficient DN3 thymocytes were not defective in generating DP thymocytes under steady state conditions or in more stringent competition assays. To determine if N3 co-operates with N1 to regulate β-selection, we generated N1;N3 compound mutants. However, N3 deficiency did not exacerbate the competitive defect of N1⁺/⁻ DN3 progenitors, demonstrating that N3 does not compensate for limiting N1 during T cell development. Finally, N3 deficiency did not attenuate T cell leukemogenesis induced by conditional expression of ICN1 in DN3 thymocytes. Importantly, we showed that in contrast to N1, N3 has a low binding affinity for DL4, the most abundant intrathymic DL ligand. Thus, despite the profound effects of ectopic ligand-independent N3 activation on T cell development and leukemogenesis, physiologically activated N3 is dispensable for both processes, likely because N3 interacts poorly with intrathymic DL4.

  8. Preoperative virtual reduction reduces femoral malrotation in the treatment of bilateral femoral shaft fractures.

    Omar, Mohamed; Suero, Eduardo M; Hawi, Nael; Decker, Sebastian; Krettek, Christian; Citak, Musa

    2015-10-01

    In bilateral femoral shaft fractures, significant malrotation (>15°) occurs in about 40 % of cases after intramedullary nailing. Most of the methods that provide rotational control during surgery are based on a comparison to the intact femur and, thus, not applicable for bilateral fractures. In this study, we evaluated if preoperative virtual reduction can help improving rotational alignment in patients with bilateral femoral shaft fractures. Seven patients with bilateral femoral shaft fractures were initially treated with external fixation of both femurs. After obtaining a CT scan of both legs, the fractures were reduced virtually using the software program VoXim®, and the amount and direction of rotational correction were calculated. Subsequently, the patients were treated by antegrade femoral nailing and rotation was corrected to the preoperatively calculated amount. After external fixation, the mean rotational difference between both legs was 15.0° ± 10.2°. Four out of seven patients had a significant malrotation over 15°. Following virtual reduction, the mean rotational difference between both legs was 2.1° ± 1.2°. After intramedullary nailing, no case of malrotation occurred and the mean rotational difference was 6.1° ± 2.8°. Preoperative virtual reduction allows determining the pretraumatic femoral antetorsion and provided useful information for the definitive treatment of bilateral femoral shaft fractures. We believe that this procedure is worth being implemented in the clinical workflow to avoid malrotation after intramedullary nailing.

  9. Femoral neck fracture following groin irradiation

    Grigsby, Perry W; Roberts, Heidi L; Perez, Carlos A

    1995-04-30

    Purpose: The incidence and risk factors are evaluated for femoral neck fracture following groin irradiation for gynecologic malignancies. Methods and Materials: The radiation therapy records of 1313 patients with advanced and recurrent cancer of the vagina, vulva, cervix, and endometrium, treated at the Mallinckrodt Institute of Radiology from 1954 to 1992, were reviewed. Median follow-up was 12.7 years. From this group, 207 patients were identified who received irradiation to the pelvis and groins with anterposterior-posterior anterior (AP-PA), 18 MV photons. Data were reviewed regarding irradiation dose to the femoral neck and other presumed risk factors including age, primary site, stage, groin node status, menopausal status, estrogen use, cigarette use, alcohol consumption, and osteoporosis. Results: The per-patient incidence of femoral neck fracture was 4.8% (10 out of 207). Four patients developed bilateral fractures. However, the cumulative actuarial incidence of fracture was 11% at 5 years and 15% at 10 years. Cox multivariate analysis of age, weight, and irradiation dose showed that only irradiation dose may be important to developing fracture. Step-wise logistic regression of presumed prognostic factors revealed that only cigarette use and x-ray evidence of osteoporosis prior to irradiation treatment were predictive of fracture. Conclusion: Femoral head fracture is a common complication of groin irradiation for gynecologic malignancies. Fracture in our database appears to be related to irradiation dose, cigarette use, and x-ray evidence of osteoporosis. Special attention should be given in treatment planning (i.e., shielding of femoral head/neck and use of appropriate electron beam energies for a portion of treatment) to reduce the incidence of this complication.

  10. Femoral neck fracture following groin irradiation

    Grigsby, Perry W.; Roberts, Heidi L.; Perez, Carlos A.

    1995-01-01

    Purpose: The incidence and risk factors are evaluated for femoral neck fracture following groin irradiation for gynecologic malignancies. Methods and Materials: The radiation therapy records of 1313 patients with advanced and recurrent cancer of the vagina, vulva, cervix, and endometrium, treated at the Mallinckrodt Institute of Radiology from 1954 to 1992, were reviewed. Median follow-up was 12.7 years. From this group, 207 patients were identified who received irradiation to the pelvis and groins with anterposterior-posterior anterior (AP-PA), 18 MV photons. Data were reviewed regarding irradiation dose to the femoral neck and other presumed risk factors including age, primary site, stage, groin node status, menopausal status, estrogen use, cigarette use, alcohol consumption, and osteoporosis. Results: The per-patient incidence of femoral neck fracture was 4.8% (10 out of 207). Four patients developed bilateral fractures. However, the cumulative actuarial incidence of fracture was 11% at 5 years and 15% at 10 years. Cox multivariate analysis of age, weight, and irradiation dose showed that only irradiation dose may be important to developing fracture. Step-wise logistic regression of presumed prognostic factors revealed that only cigarette use and x-ray evidence of osteoporosis prior to irradiation treatment were predictive of fracture. Conclusion: Femoral head fracture is a common complication of groin irradiation for gynecologic malignancies. Fracture in our database appears to be related to irradiation dose, cigarette use, and x-ray evidence of osteoporosis. Special attention should be given in treatment planning (i.e., shielding of femoral head/neck and use of appropriate electron beam energies for a portion of treatment) to reduce the incidence of this complication

  11. Molecular Characterization of Notch1 Positive Progenitor Cells in the Developing Retina.

    Galina Dvoriantchikova

    Full Text Available The oscillatory expression of Notch signaling in neural progenitors suggests that both repressors and activators of neural fate specification are expressed in the same progenitors. Since Notch1 regulates photoreceptor differentiation and contributes (together with Notch3 to ganglion cell fate specification, we hypothesized that genes encoding photoreceptor and ganglion cell fate activators would be highly expressed in Notch1 receptor-bearing (Notch1+ progenitors, directing these cells to differentiate into photoreceptors or into ganglion cells when Notch1 activity is diminished. To identify these genes, we used microarray analysis to study expression profiles of whole retinas and isolated from them Notch1+ cells at embryonic day 14 (E14 and postnatal day 0 (P0. To isolate Notch1+ cells, we utilized immunomagnetic cell separation. We also used Notch3 knockout (Notch3KO animals to evaluate the contribution of Notch3 signaling in ganglion cell differentiation. Hierarchical clustering of 6,301 differentially expressed genes showed that Notch1+ cells grouped near the same developmental stage retina cluster. At E14, we found higher expression of repressors (Notch1, Hes5 and activators (Dll3, Atoh7, Otx2 of neuronal differentiation in Notch1+ cells compared to whole retinal cell populations. At P0, Notch1, Hes5, and Dll1 expression was significantly higher in Notch1+ cells than in whole retinas. Otx2 expression was more than thirty times higher than Atoh7 expression in Notch1+ cells at P0. We also observed that retinas of wild type animals had only 14% (P < 0.05 more ganglion cells compared to Notch3KO mice. Since this number is relatively small and Notch1 has been shown to contribute to ganglion cell fate specification, we suggested that Notch1 signaling may play a more significant role in RGC development than the Notch3 signaling cascade. Finally, our findings suggest that Notch1+ progenitors--since they heavily express both pro-ganglion cell (Atoh7

  12. Use of notched beams to establish fracture criteria for beryllium

    Mayville, R.A.

    1980-01-01

    The fracture of an improved form of pure beryllium was studied under triaxial tensile stresses. This state of stress was produced by testing notched beams, which were thick enough to be in a state of plane strain at the center. A plane strain, elastic-incremental plasticity finite element program was then used to determine the stress and strain distributions at fracture. A four-point bend fixture was used to load the specimens. It was carefully designed and manufactured to eliminate virtually all of the shear stresses at the reduced section of the notched beams. The unixial properties were obtained

  13. Peripheral Osteoma of the Mandibular Notch: Report of a Case

    Iwai, Toshinori; Izumi, Toshiharu; Baba, Junichi; Maegawa, Jiro; Mitsudo, Kenji; Tohnai, Iwai

    2013-01-01

    Osteoma is a benign, slow-growing osteogenic tumor that sometimes arises from the craniomaxillofacial region, such as the sinus, temporal or jaw bones. Osteoma consists of compact or cancellous bone that may be peripheral, central or extraskeletal type. Peripheral osteoma arises from the periosteum and is commonly a unilateral, pedunculated mushroom-like mass. Peripheral osteoma of the mandible is relatively uncommon, and peripheral osteoma of the mandibular notch is extremely rare, although many cases arise from the mandibular body, angle, condyle, or coronoid process. We report here an unusual peripheral osteoma of the mandibular notch in a 78-year-old nonsyndromic female

  14. Ultra-Wideband Notched Characteristic Fed by Coplanar Waveguide

    Rastanto Hadinegoro

    2015-02-01

    Full Text Available In this paper, a novel Ultra-Wide Band (UWB notch patch antenna with co-planar waveguide (CPW fed is presented. This antenna only used one layer and the patch antenna is constructed on the first layer and back to back with CPW fed and bottom part is ground plane. The width notch is used to achieve the UWB characteristic. The results shown that the impedance bandwidth is 1130 MHz (1.662–2.792 GHz or about 50.7% for VSWR <2.

  15. Mechano sorptive behaviour of notched beams in bending

    Jensen, Signe Kamp; Hoffmeyer, Preben

    1996-01-01

    Short term bending tests with end-notched beams at constant or varying moisture content have shown an apparent contradictory dependency between moisture content and strength. The higher the moisture content the higher the strength. Varying moisture results in particularly significant differences...... and by neglecting deformation due to shear. Compression stresses perpendicular to grain in excess of 6 MPa were found in the vicinity of the notch following a period of adsorption. Similarly, small tension stresses of the order 1 MPa were registered in this area when the specimens were at their most dry condition...

  16. Study of the ultrasonic technique of elapsed time of notch

    Gomes, L.C.F.L.; Rebello, J.M.A.

    1989-01-01

    The study of the ultrasonic technique of elapsed time in the dimensionment of notch inclined of 15 and 30 degree and of depth of 5 and 10 mm using the superficial Rayleigh wave and the mode conversion, with a headstock transmitter and other receiver. The dimensionment of notch and of the binding of the piece were made with headstock in different positions. Between the various results obtained can be mentioned the increase of the dimensionment, by two techniques, with the increase of the angle and/or of the depth. (V.R.B.)

  17. Notch receptor expression in neurogenic regions of the adult zebrafish brain.

    Vanessa de Oliveira-Carlos

    Full Text Available The adult zebrash brain has a remarkable constitutive neurogenic capacity. The regulation and maintenance of its adult neurogenic niches are poorly understood. In mammals, Notch signaling is involved in stem cell maintenance both in embryonic and adult CNS. To better understand how Notch signaling is involved in stem cell maintenance during adult neurogenesis in zebrafish we analysed Notch receptor expression in five neurogenic zones of the adult zebrafish brain. Combining proliferation and glial markers we identified several subsets of Notch receptor expressing cells. We found that 90 [Formula: see text] of proliferating radial glia express notch1a, notch1b and notch3. In contrast, the proliferating non-glial populations of the dorsal telencephalon and hypothalamus rarely express notch3 and about half express notch1a/1b. In the non-proliferating radial glia notch3 is the predominant receptor throughout the brain. In the ventral telencephalon and in the mitotic area of the optic tectum, where cells have neuroepithelial properties, notch1a/1b/3 are expressed in most proliferating cells. However, in the cerebellar niche, although progenitors also have neuroepithelial properties, only notch1a/1b are expressed in a high number of PCNA [Formula: see text] cells. In this region notch3 expression is mostly in Bergmann glia and at low levels in few PCNA [Formula: see text] cells. Additionally, we found that in the proliferation zone of the ventral telencephalon, Notch receptors display an apical high to basal low gradient of expression. Notch receptors are also expressed in subpopulations of oligodendrocytes, neurons and endothelial cells. We suggest that the partial regional heterogeneity observed for Notch expression in progenitor cells might be related to the cellular diversity present in each of these neurogenic niches.

  18. Hyper-activation of Notch3 amplifies the proliferative potential of rhabdomyosarcoma cells.

    Maria De Salvo

    Full Text Available Rhabdomyosarcoma (RMS is a pediatric myogenic-derived soft tissue sarcoma that includes two major histopathological subtypes: embryonal and alveolar. The majority of alveolar RMS expresses PAX3-FOXO1 fusion oncoprotein, associated with the worst prognosis. RMS cells show myogenic markers expression but are unable to terminally differentiate. The Notch signaling pathway is a master player during myogenesis, with Notch1 activation sustaining myoblast expansion and Notch3 activation inhibiting myoblast fusion and differentiation. Accordingly, Notch1 signaling is up-regulated and activated in embryonal RMS samples and supports the proliferation of tumor cells. However, it is unable to control their differentiation properties. We previously reported that Notch3 is activated in RMS cell lines, of both alveolar and embryonal subtype, and acts by inhibiting differentiation. Moreover, Notch3 depletion reduces PAX3-FOXO1 alveolar RMS tumor growth in vivo. However, whether Notch3 activation also sustains the proliferation of RMS cells remained unclear. To address this question, we forced the expression of the activated form of Notch3, Notch3IC, in the RH30 and RH41 PAX3-FOXO1-positive alveolar and in the RD embryonal RMS cell lines and studied the proliferation of these cells. We show that, in all three cell lines tested, Notch3IC over-expression stimulates in vitro cell proliferation and prevents the effects of pharmacological Notch inhibition. Furthermore, Notch3IC further increases RH30 cell growth in vivo. Interestingly, knockdown of Notch canonical ligands JAG1 or DLL1 in RMS cell lines decreases Notch3 activity and reduces cell proliferation. Finally, the expression of Notch3IC and its target gene HES1 correlates with that of the proliferative marker Ki67 in a small cohort of primary PAX-FOXO1 alveolar RMS samples. These results strongly suggest that high levels of Notch3 activation increase the proliferative potential of RMS cells.

  19. Loss of PTB or negative regulation of Notch mRNA reveals distinct zones of Notch and actin protein accumulation in Drosophila embryo.

    Cedric S Wesley

    Full Text Available Polypyrimidine Tract Binding (PTB protein is a regulator of mRNA processing and translation. Genetic screens and studies of wing and bristle development during the post-embryonic stages of Drosophila suggest that it is a negative regulator of the Notch pathway. How PTB regulates the Notch pathway is unknown. Our studies of Drosophila embryogenesis indicate that (1 the Notch mRNA is a potential target of PTB, (2 PTB and Notch functions in the dorso-lateral regions of the Drosophila embryo are linked to actin regulation but not their functions in the ventral region, and (3 the actin-related Notch activity in the dorso-lateral regions might require a Notch activity at or near the cell surface that is different from the nuclear Notch activity involved in cell fate specification in the ventral region. These data raise the possibility that the Drosophila embryo is divided into zones of different PTB and Notch activities based on whether or not they are linked to actin regulation. They also provide clues to the almost forgotten role of Notch in cell adhesion and reveal a role for the Notch pathway in cell fusions.

  20. Loss of PTB or Negative Regulation of Notch mRNA Reveals Distinct Zones of Notch and Actin Protein Accumulation in Drosophila Embryo

    Wesley, Cedric S.; Guo, Heng; Chaudhry, Kanita A.; Thali, Markus J.; Yin, Jerry C.; Clason, Todd; Wesley, Umadevi V.

    2011-01-01

    Polypyrimidine Tract Binding (PTB) protein is a regulator of mRNA processing and translation. Genetic screens and studies of wing and bristle development during the post-embryonic stages of Drosophila suggest that it is a negative regulator of the Notch pathway. How PTB regulates the Notch pathway is unknown. Our studies of Drosophila embryogenesis indicate that (1) the Notch mRNA is a potential target of PTB, (2) PTB and Notch functions in the dorso-lateral regions of the Drosophila embryo are linked to actin regulation but not their functions in the ventral region, and (3) the actin-related Notch activity in the dorso-lateral regions might require a Notch activity at or near the cell surface that is different from the nuclear Notch activity involved in cell fate specification in the ventral region. These data raise the possibility that the Drosophila embryo is divided into zones of different PTB and Notch activities based on whether or not they are linked to actin regulation. They also provide clues to the almost forgotten role of Notch in cell adhesion and reveal a role for the Notch pathway in cell fusions. PMID:21750738

  1. CT study of avascular necrosis of femoral head in adults

    Liu Jihua; Du Yuqing; Xu Aide

    2000-01-01

    Objective: To study the early and new CT signs of avascular necrosis of femoral head in adults. Methods: The CT scans of 127 cases with this condition were analyzed. Results: There were 90 hip joints with femoral head normal in shape, including 67 femoral heads with only high-density sclerosis and 23 ones with high-density and low-density areas. In 111 hip joints, the femoral head was depressed and manifested purely high-density sclerosis in 25 and mixed-density areas in 86. Air-filled cysts appeared in 43 femoral heads. In follow-up cases, the changes in shape and density of femoral head followed some rules. Conclusion: Purely high-density sclerosis is an early sign and is of great diagnostic value combined with its special shape. Air in femoral heads is also a sign of the disease

  2. A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation

    Shih, Hung Ping; Kopp, Janel L; Sandhu, Manbir

    2012-01-01

    necessitates subsequent Sox9 downregulation and evasion from Notch activity via cell-autonomous repression of Sox9 by Ngn3. If high Notch levels are maintained, endocrine progenitors retain Sox9 and undergo ductal fate conversion. Taken together, our findings establish a novel role for Notch in initiating both...

  3. Experimental analysis of compressive notch strengthening in closed-cell aluminum alloy foam

    Antoniou, A; Onck, PR; Bastawros, Ashraf F.

    2004-01-01

    The notch strengthening effect is studied experimentally in closed cell aluminum foams. The limit loads, net section strength were found for a set of double-edge-notched (DEN) and single-edge-notched (SEN) specimens loaded in compression. In addition, the evolution of the deformation is monitored

  4. Epidermal Notch1 recruits RORγ + group 3 innate lymphoid cells to orchestrate normal skin repair

    Z. Li (Zhi); T. Hodgkinson (Tom); E.J. Gothard (Elizabeth J.); S. Boroumand (Soulmaz); R. Lamb (Rebecca); I. Cummins (Ian); P. Narang (Priyanka); A. Sawtell (Amy); J. Coles (Jenny); G. Leonov (German); A. Reboldi (Andrea); C.D. Buckley; T. Cupedo (Tom); C. Siebel (Christian); A. Bayat (Ardeshir); M. Coles (Mark); C.A. Ambler (Carrie A.)

    2016-01-01

    textabstractNotch has a well-defined role in controlling cell fate decisions in the embryo and the adult epidermis and immune systems, yet emerging evidence suggests Notch also directs non-cell-autonomous signalling in adult tissues. Here, we show that Notch1 works as a damage response signal.

  5. Down-regulation of Notch-1 by γ-secretase inhibitor suppress the ...

    Notch-1 signaling is crucial for stem cell maintenance and in a variety of tissues. Previous research has demonstrated that Notch-1 activity plays a key role in prostate tumorigenesis. However, the function of Notch-1 signaling in tumorigenesis can be either oncogene or suppressor gene. In our paper, γ- secretase inhibitor ...

  6. The pathological significance of Notch1 in oral squamous cell carcinoma.

    Yoshida, Ryoji; Nagata, Masashi; Nakayama, Hideki; Niimori-Kita, Kanako; Hassan, Wael; Tanaka, Takuji; Shinohara, Masanori; Ito, Takaaki

    2013-10-01

    Notch signaling has been reported to be involved in several types of malignant tumors; however, the role and activation mechanism of Notch signaling in oral squamous cell carcinoma (OSCC) remains poorly characterized. The purpose of this study was to elucidate the pathological significance of Notch signaling and its activation mechanism in the development and progression of OSCC. In this study, we showed that the expression of Notch1 and intracellular Notch domain (NICD) are upregulated in OSCCs. In addition, Notch1 and NICD were found to be characteristically localized at the invasive tumor front. TNF-α, a major inflammatory cytokine, significantly activated Notch signaling in vitro. In a clinicopathological analysis, Notch1 expression correlated with both the T-stage and the clinical stage. Furthermore, loss of Notch1 expression correlated with the inhibition of cell proliferation and TNF-α-dependent invasiveness in an OSCC cell line. In addition, γ-secretase inhibitor (GSI) prevented cell proliferation and TNF-α-dependent invasion of OSCC cells in vitro. These results indicate that altered expression of Notch1 is associated with increased cancer progression and that Notch1 regulates the steps involved in cell metastasis in OSCC. Moreover, inactivating Notch signaling with GSI could therefore be a useful approach for treating patients with OSCC.

  7. High NOTCH activity induces radiation resistance in non small cell lung cancer

    Theys, Jan; Yahyanejad, Sanaz; Habets, Roger; Span, Paul; Dubois, Ludwig; Paesmans, Kim; Kattenbeld, Bo; Cleutjens, Jack; Groot, Arjan J.; Schuurbiers, Olga C.J.; Lambin, Philippe; Bussink, Jan; Vooijs, Marc

    2013-01-01

    Background and purpose: Patients with advanced NSCLC have survival rates <15%. The NOTCH pathway plays an important role during lung development and physiology but is often deregulated in lung cancer, making it a potential therapeutic target. We investigated NOTCH signaling in NSCLC and hypothesized that high NOTCH activity contributes to radiation resistance. Materials and methods: NOTCH signaling in NSCLC patient samples was investigated using quantitative RT-PCR. H460 NSCLC cells with either high or blocked NOTCH activity were generated and their radiation sensitivity monitored using clonogenic assays. In vivo, xenograft tumors were irradiated and response assessed using growth delay. Microenvironmental parameters were analyzed by immunohistochemistry. Results: Patients with high NOTCH activity in tumors showed significantly worse disease-free survival. In vitro, NOTCH activity did not affect the proliferation or intrinsic radiosensitivity of NSCLC cells. In contrast, xenografts with blocked NOTCH activity grew slower than wild type tumors. Tumors with high NOTCH activity grew significantly faster, were more hypoxic and showed a radioresistant phenotype. Conclusions: We demonstrate an important role for NOTCH in tumor growth and correlate high NOTCH activity with poor prognosis and radioresistance. Blocking NOTCH activity in NSCLC might be a promising intervention to improve outcome after radiotherapy

  8. Impact of Spectral Notch Width on Neurophysiological Plasticity and Clinical Effectiveness of the Tailor-Made Notched Music Training.

    Robert Wunderlich

    Full Text Available Tinnitus, the ringing in the ears that is unrelated to any external source, causes a significant loss in quality of life, involving sleep disturbance and depression for 1 to 3% of the general population. While in the first place tinnitus may be triggered by damage to the inner ear cells, the neural generators of subjective tinnitus are located in central regions of the nervous system. A loss of lateral inhibition, tonotopical reorganization and a gain-increase in response to the sensory deprivation result in hypersensitivity and hyperactivity in certain regions of the auditory cortex. In the tailor-made notched music training (TMNMT patients listen to music from which the frequency spectrum of the tinnitus has been removed. This evokes strong lateral inhibition from neurons tuned to adjacent frequencies onto the neurons involved in the tinnitus percept. A reduction of tinnitus loudness and tinnitus-related neural activity was achieved with TMNMT in previous studies. As the effect of lateral inhibition depends on the bandwidth of the notch, in the current study we altered the notch width to find the most effective notch width for TMNMT. We compared 1-octave notch width with ½-octave and ¼-octave. Participants chose their favorite music for the training that included three month of two hours daily listening. The outcome was measured by means of standardized questionnaires and magnetoencephalography. We found a general reduction of tinnitus distress in all administered tinnitus questionnaires after the training. Additionally, tinnitus-related neural activity was reduced after the training. Nevertheless, notch width did not have an influence on the behavioral or neural effects of TMNMT. This could be due to a non-linear resolution of lateral inhibition in high frequencies.

  9. The cyclops lesion after bicruciate-retaining total knee replacement

    Mark A. Klaassen, MD, FACS

    2017-12-01

    Full Text Available The cyclops lesion is a localized anterior arthrofibrosis most commonly seen following anterior cruciate ligament reconstruction. The lesion forms at the anterior cruciate ligament insertion creating a painful extension block between femoral intercondylar notch and tibial plateau. We present 2 cases (3 knees in which cyclops lesions appeared atypically following bicruciate-retaining total knee replacement. Two lesions occurred in a single patient following bilateral knee replacement. One lesion occurred in an active sportswoman. All 3 resolved following arthroscopic debridement. We describe the presentation of this unusual complication and suggest keys to its diagnosis, treatment, and prevention. Keywords: Cyclops lesion, Bicruciate-retaining, Total knee arthroplasty, Extension deficit

  10. Dual Mechanism of Action of Resveratrol in Notch Signaling ...

    activation of Notch signaling in osteosarcoma cells. ... HeyL in U2OS cells. Treatment of U2OS cells with 20 µM concentration of resveratrol for 48 h induced a ... Cell lines and culture .... concentration of resveratrol required for induced.

  11. Notch Signaling in Prostate Cancer Cells Promotes Osteoblastic Metastasis

    2017-06-01

    information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this...function and number while inducing osteoblast proliferation. Our results suggest that Notch signaling from cancer cells promotes osteoblastic...Participants and other collaborating organizations: I initiated collaboration with Dr. Evan Keller at University of Michigan to interrogate PCa bone

  12. Dual Mechanism of Action of Resveratrol in Notch Signaling ...

    Results: The results revealed that resveratrol treatment exhibited dual mechanisms of action on the activation of Notch signaling in osteosarcoma cells. The osteosarcoma cell lines, MG-63 and U2OS, when exposed to 20 μM concentration of resveratrol for 48 h showed significant toxicity compared to untreated cells.

  13. On-line identification, flutter testing and adaptive notching of ...

    multiple modes simultaneously from sine sweep and other multifrequency data, ... envelope expansion and to adjust the notch filter frequencies and suppress aero- .... estimated frequency and damping values were compared with those ..... The current configuration results in a phase delay of (p И 0X19 s, while the Kalman.

  14. Regularized Adaptive Notch Filters for Acoustic Howling Suppression

    Gil-Cacho, Pepe; van Waterschoot, Toon; Moonen, Marc

    2009-01-01

    In this paper, a method for the suppression of acoustic howling is developed, based on adaptive notch filters (ANF) with regularization (RANF). The method features three RANFs working in parallel to achieve frequency tracking, howling detection and suppression. The ANF-based approach to howling...

  15. 105 GHz Notch Filter Design for Collective Thomson Scattering

    Furtula, Vedran; Michelsen, Poul; Leipold, Frank

    2011-01-01

    A millimeter-wave notch filter with 105-GHz center frequency, >20-GHz passband coverage, and 1-GHz rejection bandwidth has been constructed. The design is based on a fundamental rectangular waveguide with cylindrical cavities coupled by narrow iris gaps, i.e., small elongated holes of negligible...

  16. Experimental and Numerical Analysis of Notched Composites Under Tension Loading

    Aidi, Bilel; Case, Scott W.

    2015-12-01

    Experimental quasi-static tests were performed on center notched carbon fiber reinforced polymer (CFRP) composites having different stacking sequences made of G40-600/5245C prepreg. The three-dimensional Digital Image Correlation (DIC) technique was used during quasi-static tests conducted on quasi-isotropic notched samples to obtain the distribution of strains as a function of applied stress. A finite element model was built within Abaqus to predict the notched strength and the strain profiles for comparison with measured results. A user-material subroutine using the multi-continuum theory (MCT) as a failure initiation criterion and an energy-based damage evolution law as implemented by Autodesk Simulation Composite Analysis (ASCA) was used to conduct a quantitative comparison of strain components predicted by the analysis and obtained in the experiments. Good agreement between experimental data and numerical analyses results are observed. Modal analysis was carried out to investigate the effect of static damage on the dominant frequencies of the notched structure using the resulted degraded material elements. The first in-plane mode was found to be a good candidate for tracking the level of damage.

  17. Computer tomographic determination of femoral anteversion

    Jend, H.H.

    1986-01-01

    Thirty-two macerated femora were examined by CT in order to determine the degree of anteversion and to relate this to the position of the femur and to the various reference lines quoted in the literature. The accuracy of CT is the same as that of the Rippstein method, provided the following conditions are met: 1. Position of the femur with its long axis perpendicular to the image plane. 2. Demonstration of the maximal configuration of the femoral condyles to enable one to construct a tangent to the dorsal aspect of the condyle. 3. Demonstration of the head and neck by a plane which divides the neck into approximately equal portions and sections the femoral head. These conditions are more easily met, even in immobile patients, than the requirements for the Rippstein method. (orig.) [de

  18. Intracorporeal knotting of a femoral nerve catheter

    Ghanem, Mohamed

    2015-01-01

    Full Text Available Peripheral nerve catheters are effective and well-established tools to provide postoperative analgesia to patients undergoing orthopedic surgery. The performance of these techniques is usually considered safe. However, placement of nerve catheters may be associated with a considerable number of side effects and major complications have repeatedly been published. In this work, we report on a patient who underwent total knee replacement with spinal anesthesia and preoperative insertion of femoral and sciatic nerve catheters for postoperative analgesia. During insertion of the femoral catheter, significant resistance was encountered upon retracting the catheter. This occurred due to knotting of the catheter. The catheter had to be removed by operative intervention which has to be considered a major complication. The postoperative course was uneventful. The principles for removal of entrapped peripheral catheters are not well established, may differ from those for neuroaxial catheters, and range from cautious manipulation up to surgical intervention.

  19. Femoral head fracture without hip dislocation

    Aggarwal Aditya K

    2013-10-01

    Full Text Available 【Abstract】Femoral head fractures without dislocation or subluxation are extremely rare injuries. We report a neglected case of isolated comminuted fracture of femoral head without hip dislocation or subluxation of one year duration in a 36-year-old patient who sustained a high en- ergy trauma due to road traffic accident. He presented with painful right hip and inability to bear full weight on right lower limb with Harris hip score of 39. He received cementless total hip replacement. At latest follow-up of 2.3 years, functional outcome was excellent with Harris hip score of 95. Such isolated injuries have been described only once in the literature and have not been classified till now. The purpose of this report is to highlight the extreme rarity, possible mechanism involved and a novel classification system to classify such injuries. Key words: Femur head; Hip dislocation; Classification; Arthroplasty, replacement, hip

  20. Spontaneous stress fractures of the femoral neck

    Dorne, H.L.; Lander, P.H.

    1985-01-01

    The diagnosis of spontaneous stress fractures of the femoral neck, a form of insufficiency stress fracture, can be missed easily. Patients present with unremitting hip pain without a history of significant trauma or unusual increase in daily activity. The initial radiographic features include osteoporosis, minor alterations of trabecular alignment, minimal extracortical or endosteal reaction, and lucent fracture lines. Initial scintigraphic examinations performed in three of four patients showed focal increased radionuclide uptake in two and no focal abnormality in one. Emphasis is placed on the paucity of early findings. Evaluation of patients with persistent hip pain requires a high degree of clinical suspicion and close follow-up; the sequelae of undetected spontaneous fractures are subcapital fracture with displacement, angular deformity, and a vascular necrosis of the femoral head

  1. The importance of Notch signaling in peripheral T-cell lymphomas

    Kamstrup, Maria Rørbæk; Biskup, Edyta; Gjerdrum, Lise Mette Rahbek

    2014-01-01

    Peripheral T-cell lymphomas (PTLs) represent an area of high medical need. Previously, we demonstrated high expression of Notch, a known oncogene, in primary cutaneous anaplastic large cell lymphoma (ALCL). In this study, we performed immunohistochemical staining for Notch1 in lymph nodes from PTL...... cases) (p > 0.05). In the ALK+ ALCL cell line, Karpas-299, pharmacological inhibition of Notch with γ-secretase inhibitor (GSI) I was far more potent than with GSI IX, XX and XXI with regard to cell viability and apoptosis. In conclusion, PTL tumor cells have prominent Notch1 expression and treatment...... with Notch inhibitors has cytotoxic effects....

  2. Ipsilateral femoral neck and trochanter fracture

    Devdatta S Neogi

    2011-01-01

    Full Text Available Ipsilateral fractures in the neck and trochanteric region of the femur are very rare and seen in elderly osteoporotic patients. We present a case of a young man who presented with ipsilateral fracture of the femoral neck and a reverse oblique fracture in the trochanteric region following a motor vehicle accident. A possible mechanism, diagnostic challenge, and awareness required for identifying this injury are discussed.

  3. Proximal focal femoral deficiency: A case report

    Shashank Sharma

    2015-01-01

    Full Text Available Proximal focal femoral deficiency (PFFD is a rare congenital anomaly resulting in limb shortening and disability in young. The exact cause of the disease is not known and it may present as varying grades of affection involving the proximal femur and the acetabulum. Recognition of this rare abnormality on radiographs can help manage these cases better since early institution of therapy may help in achieving adequate growth of the femur.

  4. Radiofrequency ablation of two femoral head chondroblastomas

    Petsas, Theodore [Department of Radiology, University of Patras (Greece); Megas, Panagiotis [Department of Orthopaedic Surgery, University of Patras (Greece)]. E-mail: panmegas@med.upatras.gr; Papathanassiou, Zafiria [Department of Radiology, University of Patras (Greece)

    2007-07-15

    Chondroblastoma is a rare benign cartilaginous bone tumor. Surgical resection is the treatment of choice for pain relief and prevention of further growth. Open surgical techniques are associated with complications, particularly when the tumors are located in deep anatomical sites. The authors performed RF ablation in two cases of subarticular femoral head chondroblastomas and emphasize its positive impact. The clinical course, the radiological findings and the post treatment results are discussed.

  5. [Avascular necrosis of the femoral head].

    Porubský, Peter; Trč, Tomáš; Havlas, Vojtěch; Smetana, Pavel

    Avascular necrosis of the femoral head in adults is not common, but not too rare diseases. In orthopedic practice, it is one of the diseases that are causing implantation of hip replacement at a relatively early age. In the early detection and initiation of therapy can delay the implantation of prosthesis for several years, which is certainly more convenient for the patient and beneficial. This article is intended to acquaint the reader with the basic diagnostic procedures and therapy.

  6. MYCOTIC FEMORAL PSEUDOANEURYSMS FROM INTRAVENOUS DRUG ABUSE

    Vojko Flis

    2004-04-01

    Full Text Available Background. Parenteral drug abuse is the most common cause of infected femoral artery pseudoaneurysms (IFAP. This complication of intravenous drug abuse is not only limb threatening but can also be life threatening. The management of the IFAP is difficult and controversial. Generally speaking, ligation and excision of the pseudoaneurysm without revascularization is accepted procedure in majority of the patients. However it is not regarded as an appropriate procedure for cases where the high probability of amputation is expected from acute interruption of the femoral artery flow.Patients, methods and results. We present three cases of young (average 20 years, range 18–24 patients with IFAP, in which a primary reconstruction was performed due to absence of doppler signal over pedal arteries after ligation of common femoral artery. In two of them complications in form of haemorrhage and repeated infection developed in late postoperative period. The first one, had an excision and ligation while the second one had a reconstruction made by means of a silver impregnated dacron prosthesis. None of the patients required an amputation.Conclusions. Overall prognosis and prognosis of the reconstruction in parenteral drug abuse patients is uncertain because there is a high incidence of postoperative drug injection despite aggressive drug rehabilitation.

  7. Radionuclide patterns of femoral head disease

    Webber, M M; Wagner, J; Cragin, M D [California Univ., Los Angeles (USA). Dept. of Radiological Sciences

    1977-12-01

    The pattern of uptake of bone marrow specific radio-sup(99m)Tc sulfur colloid and the pattern of uptake of bone mineral specific radio-sup(99m)Tc pryophosphate may be valuable in assessing bone vascularity in diseases suspected of causing impaired blood supply, or indicate the presence of reactive bone formation. The low energy of the technetium label has been shown to be superior to /sup 18/F and /sup 85/Sr, and leads to greater imaging detail on the scans. Femoral head scanning with mineral and/or marrow specific radionuclides offers the clinician a method of evaluating the status of the femoral head and possibly an early diagnosis of avascular necrosis before roentgenographic changes occur. This study, which reports on a 5-year experience using radionuclide scanning to assess femoral head vascularity, begins with baseline or normal studies followed by variations of the normal pattern. Typical scan patterns of hip pathology described above are also presented.

  8. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

    Liu, Xin-Hua; Yao, Shen; Qiao, Rui-Fang; Levine, Alice C.; Kirschenbaum, Alexander; Pan, Jiangping; Wu, Yong; Qin, Weiping; Bauman, William A.; Cardozo, Christopher P.

    2011-01-01

    Highlights: → Nerve transection increased Notch signaling in paralyzed muscle. → Nandrolone prevented denervation-induced Notch signaling. → Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. → Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  9. Evaluation of notch effects in low cycle fatigue of alloy 718 using critical distances

    Eriksson Robert

    2018-01-01

    Full Text Available Gas turbine disks contain many notch-like features acting as stress raisers. The fatigue life based on the notch root stress may be overly conservative as the steep stress gradient in front of the notch may give rise to so-called notch support. In the current work, the theory of critical distances was applied to the prediction of the total fatigue life of low cycle fatigued, notched specimens made from alloy 718. The fatigue tests were performed at 450 °C and 550 °C. It was found that, for lives shorter than 5000–10000 cycles, the notched specimens had longer lives than would have been expected based on the notch root strain. For lives longer than 5000–10000 cycles, there were no notch support. The life prediction for notched specimens could be significantly improved by basing the prediction on the strain chosen some distance from the notch (the critical distance. An expression for calculating the critical distance based on the notch root strain was suggested.

  10. The histone deacetylase HDAC1 positively regulates Notch signaling during Drosophila wing development

    Zehua Wang

    2018-02-01

    Full Text Available The Notch signaling pathway is highly conserved across different animal species and plays crucial roles in development and physiology. Regulation of Notch signaling occurs at multiple levels in different tissues and cell types. Here, we show that the histone deacetylase HDAC1 acts as a positive regulator of Notch signaling during Drosophila wing development. Depletion of HDAC1 causes wing notches on the margin of adult wing. Consistently, the expression of Notch target genes is reduced in the absence of HDAC1 during wing margin formation. We further provide evidence that HDAC1 acts upstream of Notch activation. Mechanistically, we show that HDAC1 regulates Notch protein levels by promoting Notch transcription. Consistent with this, the HDAC1-associated transcriptional co-repressor Atrophin (Atro is also required for transcriptional activation of Notch in the wing disc. In summary, our results demonstrate that HDAC1 positively regulates Notch signaling and reveal a previously unidentified function of HDAC1 in Notch signaling.

  11. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

    Liu, Xin-Hua [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Yao, Shen; Qiao, Rui-Fang; Levine, Alice C. [Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Kirschenbaum, Alexander [Department of Urology, Mount Sinai School of Medicine, New York, NY 10029 (United States); Pan, Jiangping; Wu, Yong [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Qin, Weiping [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Bauman, William A. [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Cardozo, Christopher P., E-mail: chris.cardozo@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States)

    2011-10-14

    Highlights: {yields} Nerve transection increased Notch signaling in paralyzed muscle. {yields} Nandrolone prevented denervation-induced Notch signaling. {yields} Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. {yields} Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  12. Jagged1 is the pathological link between Wnt and Notch pathways in colorectal cancer.

    Rodilla, Verónica; Villanueva, Alberto; Obrador-Hevia, Antonia; Robert-Moreno, Alex; Fernández-Majada, Vanessa; Grilli, Andrea; López-Bigas, Nuria; Bellora, Nicolás; Albà, M Mar; Torres, Ferran; Duñach, Mireia; Sanjuan, Xavier; Gonzalez, Sara; Gridley, Thomas; Capella, Gabriel; Bigas, Anna; Espinosa, Lluís

    2009-04-14

    Notch has been linked to beta-catenin-dependent tumorigenesis; however, the mechanisms leading to Notch activation and the contribution of the Notch pathway to colorectal cancer is not yet understood. By microarray analysis, we have identified a group of genes downstream of Wnt/beta-catenin (down-regulated when blocking Wnt/beta-catenin) that are directly regulated by Notch (repressed by gamma-secretase inhibitors and up-regulated by active Notch1 in the absence of beta-catenin signaling). We demonstrate that Notch is downstream of Wnt in colorectal cancer cells through beta-catenin-mediated transcriptional activation of the Notch-ligand Jagged1. Consistently, expression of activated Notch1 partially reverts the effects of blocking Wnt/beta-catenin pathway in tumors implanted s.c. in nude mice. Crossing APC(Min/+) with Jagged1(+/Delta) mice is sufficient to significantly reduce the size of the polyps arising in the APC mutant background indicating that Notch is an essential modulator of tumorigenesis induced by nuclear beta-catenin. We show that this mechanism is operating in human tumors from Familial Adenomatous Polyposis patients. We conclude that Notch activation, accomplished by beta-catenin-mediated up-regulation of Jagged1, is required for tumorigenesis in the intestine. The Notch-specific genetic signature is sufficient to block differentiation and promote vasculogenesis in tumors whereas proliferation depends on both pathways.

  13. Stress intensity factors and weight functions for cracks in front of notches

    Fett, T.

    1993-12-01

    The knowledge of stress intensity factors for cracks at notch roots is important for the fracture mechanical treatment of real components. Stress intensity factor solutions are available only for special notches and externally applied loads. For the treatment of more complex loadings as thermal stresses near the notch root the weight function is needed in addition. In the first part of this report weight functions for cracks in front of internal notches are derived from stress intensity factor solutions under external loading available in the literature. The second part deals with cracks in front of edge notches. Limit cases of stress intensity factors are derived which allow to estimate stress intensity factors for cracks in front of internal elliptical notches with arbitrary aspect ratio of the ellipse and for external notches. (orig.) [de

  14. Application and validation of the notch master curve in medium and high strength structural steels

    Cicero, Sergio; Garcia, Tiberio [Universidad de Cantabria, Santander (Spain); Madrazo, Virginia [PCTCAN, Santander (Spain)

    2015-10-15

    This paper applies and validates the Notch master curve in two ferritic steels with medium (steel S460M) and high (steel S690Q) strength. The Notch master curve is an engineering tool that allows the fracture resistance of notched ferritic steels operating within their corresponding ductile-to-brittle transition zone to be estimated. It combines the Master curve and the Theory of critical distances in order to take into account the temperature and the notch effect respectively, assuming that both effects are independent. The results, derived from 168 fracture tests on notched specimens, demonstrate the capability of the Notch master curve for the prediction of the fracture resistance of medium and high strength ferritic steels operating within their ductile-to-brittle transition zone and containing notches.

  15. The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality

    Boskovski, Marko T; Yuan, Shiaulou; Pedersen, Nis Borbye

    2013-01-01

    to such determination. We previously identified GALNT11 as a candidate disease gene in a patient with heterotaxy, and now demonstrate, in Xenopus tropicalis, that galnt11 activates Notch signalling. GALNT11 O-glycosylates human NOTCH1 peptides in vitro, thereby supporting a mechanism of Notch activation either...... by increasing ADAM17-mediated ectodomain shedding of the Notch receptor or by modification of specific EGF repeats. We further developed a quantitative live imaging technique for Xenopus left-right organizer cilia and show that Galnt11-mediated Notch1 signalling modulates the spatial distribution and ratio...... of motile and immotile cilia at the left-right organizer. galnt11 or notch1 depletion increases the ratio of motile cilia at the expense of immotile cilia and produces a laterality defect reminiscent of loss of the ciliary sensor Pkd2. By contrast, Notch overexpression decreases this ratio, mimicking...

  16. Notch 1 as a potential therapeutic target in cutaneous T-cell lymphoma

    Kamstrup, Maria Rørbæk; Gjerdrum, Lise Mette Rahbek; Biskup, Edyta Urszula

    2010-01-01

    Deregulation of Notch signaling has been linked to the development of T-cell leukemias and several solid malignancies. Yet, it is unknown whether Notch signalling is involved in the pathogenesis of mycosis fungoides and Sezary syndrome, the most common subtypes of cutaneous T cell lymphoma....... By immunohistochemistry of 40 biopsies taken from skin lesions of mycosis fungoides and Sezary syndrome we demonstrated prominent expression of Notch1 on tumor cells, especially in the more advanced stages. The gamma-secretase inhibitor I blocked Notch signaling and potently induced apoptosis in cell lines derived from...... mycosis fungoides (MyLa) and Sezary syndrome (SeAx, HuT-78)and in primary leukemic Sézary cells. Specific downregulation of Notch1 (but not Notch2 and Notch3) by siRNA induced apoptosis in SeAx. The mechanism of apoptosis involved the inhibition of NF-kappaB, which is the most important prosurvival...

  17. Fracture Mechanics Assessment for Different Notch Sizes Using Finite Element Analysis Based on Ductile Failure Simulation

    Bae, Keun Hyung; Jeon, Jun Young; Han, Jae Jun; Nam, Hyun Suk; Lee, Dae Young; Kim, Yun Jae [Korea Univ., Seoul (Korea, Republic of)

    2016-08-15

    In this study, notch defects are evaluated using fracture mechanics. To understand the effects of notch defects, FE analysis is conducted to predict the limit load and J-integral for middle-cracked and single-edge cracked plates with various sizes of notch under tension and bending. As the radius of the notch increases, the energy release rate also increases, although the limit load remains constant. The values of fracture toughness(J{sub IC}) of SM490A are determined for various notch radii through FE simulation instead of conducting an experiment. As the radius of the notch increases, the energy release rate also increases, together with a more significant increase in fracture toughness. To conclude, as the notch radius increases, the resistance to crack propagation also increases.

  18. Incidence of Avascular Necrosis of the Femoral Head After Intramedullary Nailing of Femoral Shaft Fractures

    Kim, Ji Wan; Oh, Jong-Keon; Byun, Young-Soo; Shon, Oog-Jin; Park, Jai Hyung; Oh, Hyoung Keun; Shon, Hyun Chul; Park, Ki Chul; Kim, Jung Jae; Lim, Seung-Jae

    2016-01-01

    Abstract The goal of this study was to determine the incidence of avascular necrosis of the femoral head (AVNFH) after intramedullary nailing of femoral shaft fractures and to identify risk factors for developing AVNFH. We retrospectively reviewed all patients with femoral shaft fractures treated with antegrade intramedullary nailing at 10 institutions. Among the 703 patients enrolled, 161 patients were excluded leaving 542 patients in the study. Average age was 42.1 years with average follow-up of 26.3 months. Patient characteristics and fracture patterns as well as entry point of femoral nails were identified and the incidence of AVNFH was investigated. Patients were divided into 2 groups according to open versus closed physis, open versus closed fractures, and age (<20 versus ≥20 years). Overall incidence of AVNFH was 0.2% (1 of 542): the patient was 15-year-old boy. Of 25 patients with open physis, the incidence of AVNFH was 4%, whereas none of 517 patients with closed physis developed AVNFH (P < 0.001). The incidence of AVNFH in patients aged < 20 versus ≥20 years was 1.1% (1 of 93) and 0.0% (0 of 449), respectively (P = 0.172), which meant that the incidence of AVNFH was 0% in adult with femur shaft fracture. Of 61 patients with open fractures, the incidence of AVNFH was 0%. The number of cases with entry point at the trochanteric fossa or tip of the greater trochanter (GT) was 324 and 218, respectively, and the incidence of AVNFH was 0.3% and 0.0%, respectively (P = 0.412). In patients aged ≥20 years with isolated femoral shaft fracture, there was no case of AVNFH following antegrade intramedullary nailing regardless of the entry point. Therefore, our findings suggest that the risk of AVNFH following antegrade femoral nailing is extremely low in adult patients. PMID:26844518

  19. Ipsilateral femoral neck and shaft fractures: An overlooked association

    Daffner, R.H.; Riemer, B.L.; Butterfield, S.L.

    1991-01-01

    A total of 304 patients with injuries to the femoral shaft and ipsilateral hip presented between 1984 and 1990. Some 253 of them suffered fractures of the femoral shaft and dislocated hips or fractures of the acetabulum, and 51 of these sustained fractures of the femoral shaft and neck or trochanteric region. All of the trochanteric injuries were demonstrated on the initial radiographs. However, in 11 of the patients with combined femoral shaft and neck fractures, the diagnosis was delayed by as much as 4 weeks. This delay related to the fact that these fractures tended not to separate in the initial evaluation period and that there was external rotation of the proximal femoral fragment due to the femoral shaft fracture. (orig./GDG)

  20. Ipsilateral femoral neck and shaft fractures: An overlooked association

    Daffner, R.H. (Dept. of Diagnostic Radiology, Allegheny General Hospital, Pittsburgh, PA (USA) Medical Coll. of Pennsylvania, Pittsburgh, PA (USA)); Riemer, B.L.; Butterfield, S.L. (Dept. of Orthopedic Surgery, Allegheny General Hospital, Pittsburgh, PA (USA) Medical Coll. of Pennsylvania, Pittsburgh, PA (USA))

    1991-05-01

    A total of 304 patients with injuries to the femoral shaft and ipsilateral hip presented between 1984 and 1990. Some 253 of them suffered fractures of the femoral shaft and dislocated hips or fractures of the acetabulum, and 51 of these sustained fractures of the femoral shaft and neck or trochanteric region. All of the trochanteric injuries were demonstrated on the initial radiographs. However, in 11 of the patients with combined femoral shaft and neck fractures, the diagnosis was delayed by as much as 4 weeks. This delay related to the fact that these fractures tended not to separate in the initial evaluation period and that there was external rotation of the proximal femoral fragment due to the femoral shaft fracture. (orig./GDG).

  1. MR evaluation of femoral neck version and tibial torsion

    Koenig, James Karl; Dwek, Jerry R. [University of California, San Diego, Children' s Hospital and Health Center, Department of Radiology, San Diego, CA (United States); Pring, Maya E. [Rady Children' s Hospital, Department of Pediatric Orthopedic Surgery, San Diego, CA (United States)

    2012-01-15

    Abnormalities of femoral neck version have been associated with a number of hip abnormalities in children, including slipped capital femoral epiphysis, proximal femoral focal deficiency, coxa vara, a deep acetabulum and, rarely, developmental dysplasia of the hip. Orthopedic surgeons also are interested in quantifying the femoral neck anteversion or retroversion in children especially to plan derotational osteotomies. Historically, the angle of femoral version and tibial torsion has been measured with the use of radiography and later by CT. Both methods carry with them the risks associated with ionizing radiation. Techniques that utilize MR are used less often because of the associated lengthy imaging times. This article describes a technique using MRI to determine femoral neck version and tibial torsion with total scan times of approximately 10 min. (orig.)

  2. Computerized tomography in evaluation of decreased acetabular and femoral anteversion

    Toennis, D.; Skamel, H.J.

    2003-01-01

    Computerized tomography has received a new importance. It has been shown that decreased anteversion of femur and acetabulum, when both have decreased angles, are causing pain and osteoarthritis of the hip joint. Operative treatment should be performed before osteoarthritis develops. Exact measurements therefore are necessary. The investigation should be performed in prone position to have the pelvis lying in a defined and normal position. Femoral torsion is measured between the transverse axis of the knee and the femoral neck. The transverse axis for measurement of the femoral anteversion is defined by a rectangular line to the sagittal plane. For evaluation of the femoral anteversion in total the angle of the condyles has to be added to the femoral neck angle when the knee is found in internal rotation. Acetabular anteversion should be measured at the level where the femoral head is still in full contact and congruence with the anterior margin of the acetabulum. (orig.) [de

  3. Compartment Syndrome following Open Femoral Fracture with an Isolated Femoral Vein Injury Treated with Acute Repair

    David Walmsley

    2014-01-01

    Full Text Available Acute compartment syndrome is a surgical emergency and its diagnosis is more difficult in obtunded or insensate patients. We present the case of a 34-year-old woman who sustained a Gustilo-Anderson grade III open midshaft femur fracture with an isolated femoral vein injury treated with direct repair. She developed lower leg compartment syndrome at 48 hours postoperatively, necessitating fasciotomies. She was subsequently found to have a DVT in her femoral vein at the level of the repair and was started on therapeutic anticoagulation. This case highlights the importance of recognition of isolated venous injuries in a trauma setting as a risk factor for developing compartment syndrome.

  4. Delayed appearance of hypaesthesia and paralysis after femoral nerve block

    Stefan Landgraeber; Thomas Albrecht; Ulrich Reischuck; Marius von Knoch

    2012-01-01

    We report on a female patient who underwent an arthroscopy of the right knee and was given a continuous femoral nerve block catheter. The postoperative course was initially unremarkable, but when postoperative mobilisation was commenced, 18 hours after removal of the catheter, the patient noticed paralysis and hypaesthesia. Examination confirmed the diagnosis of femoral nerve dysfunction. Colour duplex sonography of the femoral artery and computed tomography of the lumbar spine and pelvis yie...

  5. Inhibition of fibroblast growth by Notch1 signaling is mediated by induction of Wnt11-dependent WISP-1.

    Zhao-Jun Liu

    Full Text Available Fibroblasts are an integral component of stroma and important source of growth factors and extracellular matrix (ECM. They play a prominent role in maintaining tissue homeostasis and in wound healing and tumor growth. Notch signaling regulates biological function in a variety of cells. To elucidate the physiological function of Notch signaling in fibroblasts, we ablated Notch1 in mouse (Notch1(Flox/Flox embryonic fibroblasts (MEFs. Notch1-deficient (Notch1(-/- MEFs displayed faster growth and motility rate compared to Notch1(Flox/Flox MEFs. Such phenotypic changes, however, were reversible by reconstitution of Notch1 activation via overexpression of the intracellular domain of Notch1 (NICD1 in Notch1-deficient MEFs. In contrast, constitutive activation of Notch1 signaling by introducing NICD1 into primary human dermal fibroblasts (FF2441, which caused pan-Notch activation, inhibited cell growth and motility, whereas cellular inhibition was relievable when the Notch activation was countered with dominant-negative mutant of Master-mind like 1 (DN-MAML-1. Functionally, "Notch-activated" stromal fibroblasts could inhibit tumor cell growth/invasion. Moreover, Notch activation induced expression of Wnt-induced secreted proteins-1 (WISP-1/CCN4 in FF2441 cells while deletion of Notch1 in MEFs resulted in an opposite effect. Notably, WISP-1 suppressed fibroblast proliferation, and was responsible for mediating Notch1's inhibitory effect since siRNA-mediated blockade of WISP-1 expression could relieve cell growth inhibition. Notch1-induced WISP-1 expression appeared to be Wnt11-dependent, but Wnt1-independent. Blockade of Wnt11 expression resulted in decreased WISP-1 expression and liberated Notch-induced cell growth inhibition. These findings indicated that inhibition of fibroblast proliferation by Notch pathway activation is mediated, at least in part, through regulating Wnt1-independent, but Wnt11-dependent WISP-1 expression.

  6. Notch signaling and ghost cell fate in the calcifying cystig odontogenic tumor

    Siar CH

    2011-11-01

    Full Text Available Abstract Notch signaling is an evolutionarily conserved mechanism that enables adjacent cells to adopt different fates. Ghost cells (GCs are anucleate cells with homogeneous pale eosinophilic cytoplasm and very pale to clear central areas (previous nucleus sites. Although GCs are present in a variety of odontogenic lesions notably the calcifying cystic odontogenic tumor (GCOT, their nature and process of formation remains elusive. The aim of this study was to investigate the role of Notch signaling in the cell fate specification of GCs in CCOT. Immunohistochemical staining for four Notch receptors (Notch1, Notch2, Notch3 and Notch4 and three ligands (Jagged1, Jagged2 and Delta1 was performed on archival tissues of five CCOT cases. Level of positivity was quantified as negative (0, mild (+, moderate (2+ and strong (3+. Results revealed that GCs demonstrated overexpression for Notch1 and Jagged1 suggesting that Notch1Jagged1 signaling might serve as the main transduction mechanism in cell fate decision for GCs in CCOT. Protein localizations were largely membranous and/or cytoplasmic. Mineralized GCs also stained positive implicating that the calcification process might be associated with upregulation of these molecules. The other Notch receptors and ligands were weak to absent in GCs and tumoral epithelium. Stromal endothelium and fibroblasts were stained variably positive.

  7. Aberrant Regulation of Notch3 Signaling Pathway in Polycystic Kidney Disease.

    Idowu, Jessica; Home, Trisha; Patel, Nisha; Magenheimer, Brenda; Tran, Pamela V; Maser, Robin L; Ward, Christopher J; Calvet, James P; Wallace, Darren P; Sharma, Madhulika

    2018-02-20

    Polycystic kidney disease (PKD) is a genetic disorder characterized by fluid-filled cysts in the kidney and liver that ultimately leads to end-stage renal disease. Currently there is no globally approved therapy for PKD. The Notch signaling pathway regulates cellular processes such as proliferation and de-differentiation, which are cellular hallmarks of PKD. Thus we hypothesized that the Notch pathway plays a critical role in PKD. Evaluation of protein expression of Notch signaling components in kidneys of Autosomal Recessive PKD (ARPKD) and Autosomal Dominant PKD (ADPKD) mouse models and of ADPKD patients revealed that Notch pathway members, particularly Notch3, were consistently upregulated or activated in cyst-lining epithelial cells. Notch3 expression correlated with rapidly growing cysts and co-localized with the proliferation marker, PCNA. Importantly, Notch inhibition significantly decreased forskolin-induced Notch3 activation and proliferation of primary human ADPKD cells, and significantly reduced cyst formation and growth of human ADPKD cells cultured in collagen gels. Thus our data indicate that Notch3 is aberrantly activated and facilitates epithelial cell proliferation in PKD, and that inhibition of Notch signaling may prevent cyst formation and growth.

  8. The Hippo signaling functions through the Notch signaling to regulate intrahepatic bile duct development in mammals

    Wu, Nan; Nguyen, Quy; Wan, Ying; Zhou, Tiaohao; Venter, Julie; Frampton, Gabriel A; DeMorrow, Sharon; Pan, Duojia; Meng, Fanyin; Glaser, Shannon; Alpini, Gianfranco; Bai, Haibo

    2018-01-01

    The Hippo signaling pathway and the Notch signaling pathway are evolutionary conserved signaling cascades that have important roles in embryonic development of many organs. In murine liver, disruption of either pathway impairs intrahepatic bile duct development. Recent studies suggested that the Notch signaling receptor Notch2 is a direct transcriptional target of the Hippo signaling pathway effector YAP, and the Notch signaling is a major mediator of the Hippo signaling in maintaining biliary cell characteristics in adult mice. However, it remains to be determined whether the Hippo signaling pathway functions through the Notch signaling in intrahepatic bile duct development. We found that loss of the Hippo signaling pathway tumor suppressor Nf2 resulted in increased expression levels of the Notch signaling pathway receptor Notch2 in cholangiocytes but not in hepatocytes. When knocking down Notch2 on the background of Nf2 deficiency in mouse livers, the excessive bile duct development induced by Nf2 deficiency was suppressed by heterozygous and homozygous deletion of Notch2 in a dose-dependent manner. These results implicated that Notch signaling is one of the downstream effectors of the Hippo signaling pathway in regulating intrahepatic bile duct development. PMID:28581486

  9. Manic fringe inhibits tumor growth by suppressing Notch3 degradation in lung cancer.

    Yi, Fuming; Amarasinghe, Baru; Dang, Thao P

    2013-01-01

    Notch signaling plays an essential role in development as well as cancer. We have previously shown that Notch3 is important for lung cancer growth and survival. Notch receptors are activated through the interaction with their ligands, resulting in proteolytic cleavage of the receptors. This interaction is modulated by Fringe, a family of fucose-specific β1,3 N-acetylglucosaminyltransferases that modify the extracellular subunit of Notch receptors. Studies in developmental models showed that Fringe enhances Notch's response to Delta ligands at the expense of Jagged ligands. We observed that Manic Fringe expression is down-regulated in lung cancer. Since Jagged1, a known ligand for Notch3, is often over-expressed in lung cancer, we hypothesized that Fringe negatively regulates Notch3 activation. In this study, we show that re-expression of Manic Fringe down-regulates Notch3 target genes HES1 and HeyL and reduces tumor phenotype in vitro and in vivo. The mechanism for this phenomenon appears to be related to modulation of Notch3 protein stability. Proteasome inhibition reverses Manic Fringe-induced protein turnover. Taken together, our data provide the first evidence that Manic Fringe functions as a tumor suppressor in the lung and that the mechanism of its anti-tumor activity is mediated by inhibition of Notch3 activation.

  10. The Evolution of the Maine Lobster V-Notch Practice: Cooperation in a Prisoner's Dilemma Game

    James Acheson

    2011-03-01

    Full Text Available The Maine lobster industry is experiencing record high catches because, in all probability, of an effective management program. One of the most important conservation measures is the V-notch program that allows fishermen to conserve proven breeding females by notching the tails of egg-bearing lobsters. Such marked lobsters may never be taken. Although thousands of lobster fishermen participate, it is a voluntary practice. The genesis of this practice is not easily explained, because V-notching poses a prisoner's dilemma problem that gives fishermen an incentive to avoid the practice. The most common explanations for ways to overcome prisoner's dilemma problems will not work in the case of the V-notch. An unusual combination of factors explains the V-notch program: (1 a strong belief among those in the industry that the V-notch is effective in conserving the lobster stock; (2 a low discount rate because the long-term gains from V-notching are higher than the one-time gain from defection; (3 a gain in reputation for those who V-notch. At the start of the 20th century, fishermen did not V-notch; by the end of the century, V-notching was common. We explain the change in strategies using a three-parameter evolutionary model that emphasizes the importance of culture change.

  11. In-situ tensile testing of notched poly- and oligocrystalline 316L wires

    Mitevski, Bojan [Materials Science and Engineering (ITM), Duisburg (Germany); Weiss, Sabine [Brandenburg Technical Univ., Cottbus-Senftenberg (Germany). Chair of Physical Metallurgy and Materials Science.; Fischer, Alfons [Duisburg-Essen Univ. (Germany). Materials Science and Engineering; Rush Univ. Medical Center, Chicago, IL (United States). Dept. of Orthopedics

    2017-03-01

    In-situ testing inside a scanning electron microscope is a helpful tool for detailed analyses of small sized specimens with respect to their mechanical properties and the correlated microstructural alterations. Thus, this test method is used to analyze the tensional properties of thin 316L (1.4441) wires used for microscale components, e.g., like coronary artery stents. Tensile tests were conducted on unnotched and circularly notched 316L wires (oe 0.95 mm) with a special focus on the number of grains within the cross section as well as the notch geometry. Four combinations of notch width (2 and 4 mm) and notch depth (diameter at notch root: 0.5 and 0.75 mm) were chosen. Notch depth and notch shape were adjusted by means of electrochemical polishing. Previous investigations showed, that oligocrystalline structures exhibit a different mechanical behavior compared to polycrystalline ones or single crystals. There are only a few data available on mechanical testing of oligocrystalline structures with respect to varying notch geometries. Depending on the notch geometry, grain size and, therefore, the number of grains within the notch cross section widely scattering yield- and tensile strength as well as failure elongation values were measured. However, the transition criterion between poly- and oligocrystalline behavior could be quantified to be 6 to 7 grains within the cross section.

  12. Modifiers of notch transcriptional activity identified by genome-wide RNAi

    Firnhaber Christopher B

    2010-10-01

    Full Text Available Abstract Background The Notch signaling pathway regulates a diverse array of developmental processes, and aberrant Notch signaling can lead to diseases, including cancer. To obtain a more comprehensive understanding of the genetic network that integrates into Notch signaling, we performed a genome-wide RNAi screen in Drosophila cell culture to identify genes that modify Notch-dependent transcription. Results Employing complementary data analyses, we found 399 putative modifiers: 189 promoting and 210 antagonizing Notch activated transcription. These modifiers included several known Notch interactors, validating the robustness of the assay. Many novel modifiers were also identified, covering a range of cellular localizations from the extracellular matrix to the nucleus, as well as a large number of proteins with unknown function. Chromatin-modifying proteins represent a major class of genes identified, including histone deacetylase and demethylase complex components and other chromatin modifying, remodeling and replacement factors. A protein-protein interaction map of the Notch-dependent transcription modifiers revealed that a large number of the identified proteins interact physically with these core chromatin components. Conclusions The genome-wide RNAi screen identified many genes that can modulate Notch transcriptional output. A protein interaction map of the identified genes highlighted a network of chromatin-modifying enzymes and remodelers that regulate Notch transcription. Our results open new avenues to explore the mechanisms of Notch signal regulation and the integration of this pathway into diverse cellular processes.

  13. Analysis of the Charpy V-notch test for welds

    Tvergaard, Viggo; Needleman, A.

    2000-01-01

    The ductile-brittle transition for a weld is investigated by numerical analyses of Charpy impact specimens. The material response is characterized by an elastic-viscoplastic constitutive relation for a porous plastic solid, with adiabatic heating due to plastic dissipation and the resulting thermal...... softening accounted for. The onset of cleavage is taken to occur when a critical value of the maximum principal stress is attained. The effect of weld strength undermatch or overmatch is investigated for a comparison material, and analyses are also carried out based on experimentally determined flow...... strength variations in a weldment in a HY100 steel. The predicted work to fracture shows a strong sensitivity to the location of the notch relative to the weld, with the most brittle behavior for a notch close to the narrow heat affected zone. The analyses illustrate the strong dependence of the transition...

  14. The effect of notches and pits on corrosion fatigue strength

    Tatner, Ian

    An investigation has been undertaken to examine the fatigue behaviour of two martensitic steels in air and aggressive environments. The steels studied are, 18% Ni marageing steel and FV520B, the later being a stainless steel turbine blade material and the former being a marageing steel that suffers general corrosion in mild environments. Both steels were heat treated to give similar tensile strength.The design and manufacture of an autoclave allowed push-pull fatigue tests to be conducted in aggressive environments at elevated temperatures.Corrosion potential was monitored using a three electrode cell and was controlled during testing. Base-line fatigue tests were conducted with a range of constant corrosion potentials, using both notched and plain FV520B specimens. In addition fatigue tests with pulsed corrosion potential were performed to asses the effect of transient corrosion conditions on the corrosion fatigue strength. The pulsed tests were designed to simulate service transients in the oxygen content and general chemical hostility in the condensing steam environment during start-up and shut down of the steam turbine.Post test examination of fractured samples was performed using Scanning Electron Microscopy (SEM) and optical microscope techniques. The fractography results were used to quantify microstructural and fracture features of the steels.A model based on the size and geometry of the initial corrosion pitting has been proposed to asses the fatigue life of FV520B in an aggressive environment.The effect of pitting on the corrosion fatigue strength of FV520B has been modelled using linear elastic fracture mechanics (LEFM) type approach. The model has shown a good correlation between predicted fatigue lives with experimental results.The results suggest that the fatigue life is governed by the mechanical stress concentrating effect of the pits rather than the electrochemical damage caused by the environment.Finite Element Analysis (FEA) of the notch allowed

  15. To study the role of dynamic magnetic resonance imaging in assessing the femoral head vascularity in intracapsular femoral neck fractures

    Kaushik, Abhishek, E-mail: abhiortho27@gmail.co [Department of Orthopedics, 513, Thermal Colony, Sector-22, Faridabad 121005, Haryana (India); Sankaran, Balu; Varghese, Mathew [Department of Orthopedics, St Stephen' s Hospital, Tis hazari, Delhi, New Delhi 110054 (India)

    2010-09-15

    Intracapsular femoral neck fractures remain unsolved fractures even after improvement in techniques of diagnosis and internal fixation. Individuals who sustain displaced femoral neck fractures are at high risk of developing avascular necrosis and non-union. Although several methods for predicting the viability of femoral head have been reported, they are not effective or widely used because of unreliability, potential complications and technical difficulties. Dynamic MRI was introduced in the recent past as a simple, non-invasive technique to predict the femoral head viability after the femoral neck fractures. In this study role of dynamic MRI was studied in 30 patients with 31 intracapsular femoral neck fractures. Fractures were divided in to three types according to dynamic curve patterns on MRI evaluation and were followed up for 6 months to 2 years to observe the final outcome. Sensitivity, Specificity and the Accuracy of dynamic MRI in predicting vascularity after femoral neck fracture are 87%, 88% and 87%, respectively. Type A or Type B curve pattern is a positive factor to successful osteosynthesis with p value <0.0001 (Chi-square test). This is a statistically significant value. From this finding it can be suggested that the reliability of dynamic curves A and B in predicting maintained vascularity of femoral head is high. This investigation can be used to predict the vascularity of femoral head after intracapsular femoral neck fractures. There was a good correlation between the outcomes of fractures and dynamic MRI curves done within 48 h of injury. This signifies the role of dynamic MRI in predicting the vascularity of femoral head as early as 48 h. A treatment algorithm can be suggested on the basis of dynamic MRI curves. The fractures with Type C dynamic curve should be considered as fractures with poor vascularity of femoral head and measures to enhance the vascularity of femoral head along with rigid internal fixation should be undertaken to promote

  16. To study the role of dynamic magnetic resonance imaging in assessing the femoral head vascularity in intracapsular femoral neck fractures

    Kaushik, Abhishek; Sankaran, Balu; Varghese, Mathew

    2010-01-01

    Intracapsular femoral neck fractures remain unsolved fractures even after improvement in techniques of diagnosis and internal fixation. Individuals who sustain displaced femoral neck fractures are at high risk of developing avascular necrosis and non-union. Although several methods for predicting the viability of femoral head have been reported, they are not effective or widely used because of unreliability, potential complications and technical difficulties. Dynamic MRI was introduced in the recent past as a simple, non-invasive technique to predict the femoral head viability after the femoral neck fractures. In this study role of dynamic MRI was studied in 30 patients with 31 intracapsular femoral neck fractures. Fractures were divided in to three types according to dynamic curve patterns on MRI evaluation and were followed up for 6 months to 2 years to observe the final outcome. Sensitivity, Specificity and the Accuracy of dynamic MRI in predicting vascularity after femoral neck fracture are 87%, 88% and 87%, respectively. Type A or Type B curve pattern is a positive factor to successful osteosynthesis with p value <0.0001 (Chi-square test). This is a statistically significant value. From this finding it can be suggested that the reliability of dynamic curves A and B in predicting maintained vascularity of femoral head is high. This investigation can be used to predict the vascularity of femoral head after intracapsular femoral neck fractures. There was a good correlation between the outcomes of fractures and dynamic MRI curves done within 48 h of injury. This signifies the role of dynamic MRI in predicting the vascularity of femoral head as early as 48 h. A treatment algorithm can be suggested on the basis of dynamic MRI curves. The fractures with Type C dynamic curve should be considered as fractures with poor vascularity of femoral head and measures to enhance the vascularity of femoral head along with rigid internal fixation should be undertaken to promote

  17. Surgery for pathological proximal femoral fractures, excluding femoral head and neck fractures: resection vs. stabilisation.

    Zacherl, Max; Gruber, Gerald; Glehr, Mathias; Ofner-Kopeinig, Petra; Radl, Roman; Greitbauer, Manfred; Vecsei, Vilmos; Windhager, Reinhard

    2011-10-01

    Pathological femoral head and neck fractures are commonly treated by arthroplasty. Treatment options for the trochanteric region or below are not clearly defined. The purpose of this retrospective, comparative, double-centre study was to analyse survival and influences on outcome according to the surgical technique used to treat pathological proximal femoral fractures, excluding fractures of the femoral head and neck. Fifty-nine patients with 64 fractures were operated up on between 1998 and 2004 in two tertiary referral centres and divided into two groups. One group (S, n = 33) consisted of patients who underwent intramedullary nailing alone, and the other group (R, n = 31) consisted of patients treated by metastatic tissue resection and reconstruction by means of different implants. Median survival was 12.6 months with no difference between groups. Surgical complications were higher in the R group (n = 7) vs. the S group (n = 3), with no statistically significant difference. Patients with surgery-related complications had a higher survival rate (p = 0.049), as did patients with mechanical implant failure (p = 0.01). Survival scoring systems did not correlate with actual survival. Resection of metastases in patients with pathological fractures of the proximal femur, excluding femoral head and neck fractures, has no influence on survival. Patients with long postoperative survival prognosis are at risk of implant-related complications.

  18. Self-designed femoral neck guide pin locator for femoral neck fractures.

    Xia, Shengli; Wang, Ziping; Wang, Minghui; Wu, Zuming; Wang, Xiuhui

    2014-01-01

    Closed reduction and fixation with 3 cannulated screws is a widely accepted surgery for the treatment of femoral neck fractures. However, how to obtain optimal screw placement remains unclear. In the current study, the authors designed a guide pin positioning system for femoral neck fracture cannulated screw fixation and examined its application value by comparing it with freehand guide needle positioning and with general guide pin locator positioning provided by equipment manufacturers. The screw reset rate, screw parallelism, triangle area formed by the link line of the entry point of 3 guide pins, and maximum vertical load bearing of the femoral neck after internal fixation were recorded. As expected, the triangle area was largest in the self-designed positioning group, followed by the general positioning group and the freehand positioning group. The difference among the 3 groups was statistically significant (P.05). The authors’ self-designed guide pin positioning system has the potential to accurately insert cannulated screws in femoral neck fractures and may reduce bone loss and unnecessary radiation.

  19. Notch sensitivity of cast AZ31 magnesium alloy

    Kunz, Ludvík; Lukáš, Petr; Estrin, Y.; Zúberová, Z.

    2005-01-01

    Roč. 12, č. 3 (2005), s. 88-91 ISSN 1335-0803. [Degradácia konštrukčných materiálov 2005. Terchová - Biely Potok, 05.09.2005-07.09.2005] R&D Projects: GA MŠk(CZ) 1P05ME804 Institutional research plan: CEZ:AV0Z20410507 Keywords : notch sensitivity * magnesium alloy * fatigue lifetime Subject RIV: JG - Metallurgy

  20. Hierarchical object class representation using holes and notches

    Osbourn, G.C.

    1989-01-01

    A general representation approach is described which employs a hierarchy of holes and notches. A matching procedure is also described which allows non-ideal image hierarchies to be matched to class representations. The representation and matching methods are demonstrated on a set of handgun photographs. Examples of handguns which are different in detail are shown to exhibit the same class characteristics, while other similarly shaped objects are correctly distinguished from the handgun class. 6 refs., 8 figs.

  1. Case Study of Crack Initiation from Bi-material Notches

    Klusák, Jan; Knésl, Zdeněk

    2011-01-01

    Roč. 452-453, - (2011), s. 449-452 ISSN 1013-9826. [Fracture and Damage Mechanics /9./. Nagasaki, 20.09.2010-22.09.2010] R&D Projects: GA ČR GAP108/10/2049; GA ČR GA101/08/0994 Institutional research plan: CEZ:AV0Z20410507 Keywords : Crack initiation * bi-material notch * fracture mechanics Subject RIV: JL - Materials Fatigue, Friction Mechanics

  2. Frequency Agile Microwave Photonic Notch Filter in a Photonic Chip

    2016-10-21

    Interference mitigation is crucial in modern radiofrequency (RF) communications systems with dynamically changing operating frequencies, such as cognitive...frequency measurement (IFM) system was also explored. 4. Results and discussions: a. High extinction tunable notch filter in a chalcogenide chip [Optica...Figure 2(b, lower). The measured interferer suppression in this case was 47 dB, limited by the noise floor of the measurements . This paper is in the

  3. Biogeometry of femoral neck for implant placement

    Patwa J

    2006-01-01

    Full Text Available Background : Treatment of fracture neck femur with three cannulated cancellous screws in an apex proximal configuration is practised in many parts of the world. Methods : Dimensions of femoral neck at the middle of transcervical neck using CT scan (live neck and vernier caliper (dry cadeveric neck in 20 subjects respectively were measured. Results : Inferior half of the neck is narrower than superior half. Conclusion : Biogeometry of the neck of femur does not accomodate two inferior screws and thus fixation of fracture neck femur with three canulated cancellous screws in an apex distal configuration is recommended.

  4. Superficial femoral artery: current treatment options

    Tepe, Gunnar; Schmehl, Joerg; Heller, Stephan; Wiesinger, Benjamin; Claussen, Claus D.; Duda, Stephan H.

    2006-01-01

    Treatment of the superficial femoral artery (SFA) has been among the least effective of all endovascular procedures in terms of long-term patency. The relatively small vessel lumen, in conjunction with a high plaque burden, slow flow, and a high frequency of primary occlusions, contributes to a considerable rate of acute technical failures. Because of these technical limitations a much effort has been made during the past years. This manuscript should summarize the hopes and limitations of different approaches such as brachytherapy, cutting balloons, stents and stent grafts, drug-eluting stents, and drug-coated balloons. (orig.)

  5. [Treatment of avascular necrosis of femoral head after femoral neck fracture with pedicled iliac bone graft].

    Wang, Benjie; Zhao, Dewei; Guo, Lin; Yang, Lei; Li, Zhigang; Cui, Daping; Tian, Fengde; Liu, Baoyi

    2011-05-01

    To explore the effectiveness of pedicled iliac bone graft transposition for treatment of avascular necrosis of femoral head (ANFH) after femoral neck fracture. Between June 2002 and December 2006, 22 cases (22 hips, 16 left hips and 6 right hips) of ANFH after femoral neck fracture were treated with iliac bone graft pedicled with ascending branch of the lateral femoral circumflex vessels. There were 18 males and 4 females with an age range from 28 to 48 years (mean, 37.5 years). The time from injury to internal fixation was 2-31 days, and all fractures healed within 12 months after internal fixation. The ANFH was diagnosed at 15-40 months (mean, 22 months) after internal fixation. The ANFH duration was 3-11 months (mean, 8 months). According to Association Research Circulation Osseous (ARCO) staging system, 2 hips were classified as stage IIa, 3 hips as stage IIb, 3 hips as stage IIc, 3 hips as stage IIIa, 7 hips as stage IIIb, and 4 hips as stage IIIc. The preoperative Harris hip score (HHS) was 64.10 +/- 5.95. All incisions healed by first intention and the patients had no complication of lung embolism, sciatic nerve injury, lower limb deep venous thrombosis, and numbness and pain of donor site. All patients were followed up 2.5 to 6.3 years (mean, 4.8 years). The fracture healing time was 8-12 months, and no femoral neck fracture recurred. The HHS was 90.20 +/- 5.35 at last follow-up, showing significant difference when compared with the preoperative value (t = -18.447, P = 0.000). The hip function were excellent in 11 hips, good in 10 hips, fair in 1 hip, and the excellent and good rate was 95.5%. Four hips were radiographically progressed in ARCO staging, 18 hips remained stable with a stable rate of 81.8%. Pedicled iliac bone graft transposition is an ideal option for treatment of ANFH after internal fixation of femoral neck fracture for the advantages of femoral head revascularization, sufficient cancellous bone supply, and relatively simple procedure.

  6. Magnetic domain wall motion in notch patterned permalloy nanowire devices

    Chen, Ting-Chieh; Kuo, Cheng-Yi; Mishra, Amit K.; Das, Bipul; Wu, Jong-Ching, E-mail: phjcwu@cc.ncue.edu.tw

    2015-11-01

    We report a study of magnetization reversal process of notch-patterned permalloy (Py) nanowires (NWs) by using an in-situ magnetic force microscopy (MFM). Three neighboring straight NWs and an individual straight NW with discs connected to the wires ends are fabricated by standard electron beam lithography through a lift-off technique. MFM images are taken in the presence of an in-plane magnetic field applied along the wires length. As a result, the nucleation, pinning and depinning of domain walls (DWs) along the NW are observed. The artificial constraints (notch) in such symmetrical geometry of NWs indeed serve as pinning sites to pin the DWs. The nature of magnetization reversal, pinning field and depinning field for the DWs that are observed in these permalloy NWs, indicate the key roles of notch depth, the terminal connection structure of NW end and the inter-wire interaction among the NWs. The in-situ MFM measurements are examined with the micromagnetic simulations. Consequently, good agreements are obtained for the DW structures and the effect of DWs pining/depinning, however a dissimilarity in experimental and simulation observations for the direction of propagation of DWs in NWs needs further investigation.

  7. Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells

    Dontu, Gabriela; Jackson, Kyle W; McNicholas, Erin; Kawamura, Mari J; Abdallah, Wissam M; Wicha, Max S

    2004-01-01

    Notch signaling has been implicated in the regulation of cell-fate decisions such as self-renewal of adult stem cells and differentiation of progenitor cells along a particular lineage. Moreover, depending on the cellular and developmental context, the Notch pathway acts as a regulator of cell survival and cell proliferation. Abnormal expression of Notch receptors has been found in different types of epithelial metaplastic lesions and neoplastic lesions, suggesting that Notch may act as a proto-oncogene. The vertebrate Notch1 and Notch4 homologs are involved in normal development of the mammary gland, and mutated forms of these genes are associated with development of mouse mammary tumors. In order to determine the role of Notch signaling in mammary cell-fate determination, we have utilized a newly described in vitro system in which mammary stem/progenitor cells can be cultured in suspension as nonadherent 'mammospheres'. Notch signaling was activated using exogenous ligands, or was inhibited using previously characterized Notch signaling antagonists. Utilizing this system, we demonstrate that Notch signaling can act on mammary stem cells to promote self-renewal and on early progenitor cells to promote their proliferation, as demonstrated by a 10-fold increase in secondary mammosphere formation upon addition of a Notch-activating DSL peptide. In addition to acting on stem cells, Notch signaling is also able to act on multipotent progenitor cells, facilitating myoepithelial lineage-specific commitment and proliferation. Stimulation of this pathway also promotes branching morphogenesis in three-dimensional Matrigel cultures. These effects are completely inhibited by a Notch4 blocking antibody or a gamma secretase inhibitor that blocks Notch processing. In contrast to the effects of Notch signaling on mammary stem/progenitor cells, modulation of this pathway has no discernable effect on fully committed, differentiated, mammary epithelial cells. These studies

  8. Magnetic resonance evaluation of the knee in children and adolescents with achondroplasia

    Akyol, Yakup; Averill, Lauren W.; Atanda, Alfred; Mackenzie, William G.; Kecskemethy, Heidi H.; Bober, Michael B.

    2015-01-01

    Achondroplasia is the most common form of skeletal dysplasia. Although the radiographic features are well described, MRI features of the knee in achondroplasia have not been reported. To describe common MRI characteristics of the knee joint in symptomatic children and adolescents with achondroplasia. We retrospectively evaluated 10 knee MRI examinations in 8 children and young adults (age range 11-20 years, mean 16.3 years) with achondroplasia. We measured modified Insall-Salvati index, knee flexion angle, anterior cruciate ligament (ACL)-Blumensaat line angle, ACL-tibial angle, posterior cruciate ligament (PCL) angle, intercondylar notch width index, and intercondylar notch depth index. We compared our findings with an age- and gender-matched control group of 20 children (age range 15-18 years; mean 16 years) with normal knee MRIs. All 10 knees in the achondroplasia group had discoid lateral meniscus; 8 meniscal tears were identified. Patella baja was present in half of the study cases. Greater knee flexion and increased ACL-Blumensaat line and PCL angles were seen in all achondroplasia knees. ACL-tibial angle was similar in the study and in the control group. Children with achondroplasia had deeper A-shape femoral notches that extended more anteriorly than those seen in the control group. MRI findings were confirmed in all seven knees with arthroscopic correlation. Discoid lateral meniscus, often with tear, is a consistent feature in knee MRIs of symptomatic children and adolescents with achondroplasia. Other findings include patella baja, knee flexion, deep A-shape intercondylar notch, increased ACL-Blumensaat line angle and taut PCL. (orig.)

  9. Magnetic resonance evaluation of the knee in children and adolescents with achondroplasia.

    Akyol, Yakup; Averill, Lauren W; Atanda, Alfred; Kecskemethy, Heidi H; Bober, Michael B; Mackenzie, William G

    2015-06-01

    Achondroplasia is the most common form of skeletal dysplasia. Although the radiographic features are well described, MRI features of the knee in achondroplasia have not been reported. To describe common MRI characteristics of the knee joint in symptomatic children and adolescents with achondroplasia. We retrospectively evaluated 10 knee MRI examinations in 8 children and young adults (age range 11-20 years, mean 16.3 years) with achondroplasia. We measured modified Insall-Salvati index, knee flexion angle, anterior cruciate ligament (ACL)-Blumensaat line angle, ACL-tibial angle, posterior cruciate ligament (PCL) angle, intercondylar notch width index, and intercondylar notch depth index. We compared our findings with an age- and gender-matched control group of 20 children (age range 15-18 years; mean 16 years) with normal knee MRIs. All 10 knees in the achondroplasia group had discoid lateral meniscus; 8 meniscal tears were identified. Patella baja was present in half of the study cases. Greater knee flexion and increased ACL-Blumensaat line and PCL angles were seen in all achondroplasia knees. ACL-tibial angle was similar in the study and in the control group. Children with achondroplasia had deeper A-shape femoral notches that extended more anteriorly than those seen in the control group. MRI findings were confirmed in all seven knees with arthroscopic correlation. Discoid lateral meniscus, often with tear, is a consistent feature in knee MRIs of symptomatic children and adolescents with achondroplasia. Other findings include patella baja, knee flexion, deep A-shape intercondylar notch, increased ACL-Blumensaat line angle and taut PCL.

  10. Magnetic resonance evaluation of the knee in children and adolescents with achondroplasia

    Akyol, Yakup; Averill, Lauren W. [Nemours/Alfred I. duPont Hospital for Children, Department of Medical Imaging, Wilmington, DE (United States); Atanda, Alfred; Mackenzie, William G. [Nemours/Alfred I. duPont Hospital for Children, Department of Orthopedics, Wilmington, DE (United States); Kecskemethy, Heidi H. [Nemours/Alfred I. duPont Hospital for Children, Department of Medical Imaging, Wilmington, DE (United States); Nemours/Alfred I. duPont Hospital for Children, Department of Biomedical Research, Wilmington, DE (United States); Bober, Michael B. [Nemours/Alfred I. duPont Hospital for Children, Division of Genetics, Department of Pediatrics, Wilmington, DE (United States)

    2015-06-15

    Achondroplasia is the most common form of skeletal dysplasia. Although the radiographic features are well described, MRI features of the knee in achondroplasia have not been reported. To describe common MRI characteristics of the knee joint in symptomatic children and adolescents with achondroplasia. We retrospectively evaluated 10 knee MRI examinations in 8 children and young adults (age range 11-20 years, mean 16.3 years) with achondroplasia. We measured modified Insall-Salvati index, knee flexion angle, anterior cruciate ligament (ACL)-Blumensaat line angle, ACL-tibial angle, posterior cruciate ligament (PCL) angle, intercondylar notch width index, and intercondylar notch depth index. We compared our findings with an age- and gender-matched control group of 20 children (age range 15-18 years; mean 16 years) with normal knee MRIs. All 10 knees in the achondroplasia group had discoid lateral meniscus; 8 meniscal tears were identified. Patella baja was present in half of the study cases. Greater knee flexion and increased ACL-Blumensaat line and PCL angles were seen in all achondroplasia knees. ACL-tibial angle was similar in the study and in the control group. Children with achondroplasia had deeper A-shape femoral notches that extended more anteriorly than those seen in the control group. MRI findings were confirmed in all seven knees with arthroscopic correlation. Discoid lateral meniscus, often with tear, is a consistent feature in knee MRIs of symptomatic children and adolescents with achondroplasia. Other findings include patella baja, knee flexion, deep A-shape intercondylar notch, increased ACL-Blumensaat line angle and taut PCL. (orig.)

  11. Notch inhibition counteracts Paneth cell death in absence of caspase-8.

    Jeon, M K; Kaemmerer, E; Schneider, U; Schiffer, M; Klaus, C; Hennings, J; Clahsen, T; Ackerstaff, T; Niggemann, M; Schippers, A; Longerich, T; Sellge, G; Trautwein, C; Wagner, N; Liedtke, C; Gassler, N

    2018-05-16

    Opposing activities of Notch and Wnt signaling regulate mucosal barrier homeostasis and differentiation of intestinal epithelial cells. Specifically, Wnt activity is essential for differentiation of secretory cells including Wnt3-producing Paneth cells, whereas Notch signaling strongly promotes generation of absorptive cells. Loss of caspase-8 in intestinal epithelium (casp8 ∆int ) is associated with fulminant epithelial necroptosis, severe Paneth cell death, secondary intestinal inflammation, and an increase in Notch activity. Here, we found that pharmacological Notch inhibition with dibenzazepine (DBZ) is able to essentially rescue the loss of Paneth cells, deescalate the inflammatory phenotype, and reduce intestinal permeability in casp8 ∆int mice. The secretory cell metaplasia in DBZ-treated casp8 ∆int animals is proliferative, indicating for Notch activities partially insensitive to gamma-secretase inhibition in a casp8 ∆int background. Our data suggest that casp8 acts in the intestinal Notch network.

  12. Optical stress investigations of notched bars with superimposed types of loads

    Richard, H.A.; Theis, W.

    1982-01-01

    Starting from the notch effect for various types of load, notch stresses are determined by optical methods for superimposed tensile and shearing stress and for superimposed tensile and bending stress. The superimposed stresses are induced by a device developed at the Technical Mechanics Department of Kaiserslautern University; only tensile stress needs to be applied to this testing device. The investigations have shown that in notched bars subject to superimposed tensile and shearing stress, stress increases will be higher than the maximum values of the two types of stress. For superimposed tensile and bending stress, notches on the outer side of the test piece and eccentric notches on the inner side may lead to a considerable stress increase. However, the stress distribution can be improved by an optimum arrangement of notches. (orig.) [de

  13. Notch size effects on high cycle fatigue limit stress of Udimet 720

    Ren Weiju; Nicholas, Theodore

    2003-01-01

    Notch size effects on the high cycle fatigue (HCF) limit stress of Ni-base superalloy Udimet 720 were investigated on cylindrical specimens with three notch sizes of the same stress concentration factor K t =2.74. The HCF limit stress corresponding to a life of 10 6 cycles was experimentally determined at a stress ratio of 0.1 and a frequency of 25 Hz at room temperature. The stresses were calculated using finite element analysis (FEA) and the specimens analyzed using scanning electron microscopy (SEM). Test results show that at the same K t value, notch size can slightly affect the HCF limit stress of U720 when notch root plasticity occurs. FEA and SEM results reveal that the notch size effects are influenced by a complicated combination of the stress and plastic strain fields at the notch tip, the nominal stress, and the effects of prior plastic deformation on fatigue crack initiation

  14. Notch constraint effects on the dynamic fracture toughness of an unaged beta titanium alloy

    Rack, H.J.

    1975-01-01

    The influence of notch included angle and root radius on the apparent dynamic fracture toughness of an unaged metastable beta titanium alloy, Ti--3Al--8V--6Cr--4Zr--4Mo, has been examined. The apparent fracture toughness, K/sub Id/(rho), increases with both notch radius, rho and included angle, ω. These results have been compared with the theoretical predictions of Tetelman, et al. and Smith. The comparisons show that neither theory accurately describes the effect of varying notch constraint on the apparent dynamic fracture toughness. Although preliminary considerations indicate that qualitative descriptions of notch acuity effects may be given by recent finite element analysis of the stress and strain distributions below a notch root, there is presently no quantitative basis for determining the true dynamic fracture toughness of materials from the results of blunt notch experiments. (auth)

  15. Notch lineages and activity in intestinal stem cells determined by a new set of knock-in mice.

    Silvia Fre

    Full Text Available The conserved role of Notch signaling in controlling intestinal cell fate specification and homeostasis has been extensively studied. Nevertheless, the precise identity of the cells in which Notch signaling is active and the role of different Notch receptor paralogues in the intestine remain ambiguous, due to the lack of reliable tools to investigate Notch expression and function in vivo. We generated a new series of transgenic mice that allowed us, by lineage analysis, to formally prove that Notch1 and Notch2 are specifically expressed in crypt stem cells. In addition, a novel Notch reporter mouse, Hes1-EmGFP(SAT, demonstrated exclusive Notch activity in crypt stem cells and absorptive progenitors. This roster of knock-in and reporter mice represents a valuable resource to functionally explore the Notch pathway in vivo in virtually all tissues.

  16. Application of FIB technique to introduction of a notch into a carbon fiber for direct measurement of fracture toughness

    Ogihara, S; Imafuku, Y; Yamamoto, R; Kogo, Y

    2009-01-01

    For the direct measurement of the fracture toughness of the carbon fiber, a new technique was proposed and examined its applicability. At first, machining condition of the notch was examined. The notch was introduced using focused ion beam (FIB). The ion beam can be electronically scanned to introduce a sharp notch on the carbon fiber. Notches with various notch width and length were introduced by changing beam and scanning conditions. Tensile tests on notched carbon fibers were carried out following the test method for carbon fiber monofilaments. Fractured specimens were successfully corrected without secondary damage using protection films. SEM observations revealed that a crack propagated from a notch-tip, and notch size was able to be determined successfully. Effect of notch root radius was also examined to investigate the validity of the fracture toughness obtained by this method.

  17. Comparison of Radial Access, Guided Femoral Access, and Non-Guided Femoral Access Among Women Undergoing Percutaneous Coronary Intervention.

    Koshy, Linda M; Aberle, Laura H; Krucoff, Mitchell W; Hess, Connie N; Mazzaferri, Ernest; Jolly, Sanjit S; Jacobs, Alice; Gibson, C Michael; Mehran, Roxana; Gilchrist, Ian C; Rao, Sunil V

    2018-01-01

    This study was conducted to determine the association between radial access, guided femoral access, and non-guided femoral access on postprocedural bleeding and vascular complications after percutaneous coronary intervention (PCI). Bleeding events and major vascular complications after PCI are associated with increased morbidity, mortality, and cost. While the radial approach has been shown to be superior to the femoral approach in reducing bleeding and vascular complications, whether the use of micropuncture, fluoroscopy, or ultrasound mitigates these differences is unknown. We conducted a post hoc analysis of women in the SAFE-PCI for Women trial who underwent PCI and had the access method identified (n = 643). The primary endpoint of postprocedure bleeding or vascular complications occurring within 72 hours or at discharge was adjudicated by an independent clinical events committee and was compared based on three categories of access technique: radial, guided femoral (fluoroscopy, micropuncture, ultrasound), or non-guided femoral (none of the aforementioned). Differences between the groups were determined using multivariate logistic regression using radial access as the reference. Of the PCI population, 330 underwent radial access, 228 underwent guided femoral access, and 85 underwent non-guided femoral access. There was a statistically significant lower incidence of the primary endpoint with radial access vs non-guided femoral access; however, there was no significant difference between radial approach and femoral access guided by fluoroscopy, micropuncture, or ultrasound. This post hoc analysis demonstrates that while radial access is safer than non-guided femoral access, guided femoral access appears to be associated with similar bleeding events or vascular complications as radial access.

  18. Current indications for open Kuntscher nailing of femoral shaft ...

    Current indications for open Kuntscher nailing of femoral shaft fractures. A S Bajwa FCS(SA)ORTH. E Schnaid FCS(SA)ORTH. M E B Sweet MD PhD(rned). University of Witwatersrand, Johannesburg, South Africa. Key Words: Kuntscher nail, intramedullary nail, femoral fracture. We retrospectively reviewed 32 patients with.

  19. Bilateral impacted femoral neck fracture in a renal disease patient ...

    Spontaneous bilateral femoral neck facture in a renal disease patient is not common. We report a case of 47-year-old female patient with chronic renal failure and on regular hemodialysis for the past 5 years who sustained bilateral impacted femoral neck fracture without history of trauma and injury and refused any surgical ...

  20. Slipped capital femoral epiphysis: A modern treatment protocol

    Slavković Nemanja

    2009-01-01

    Full Text Available The treatment of a patient with slipped capital femoral epiphysis begins with an early diagnosis and accurate classification. On the basis of symptom duration, clinical findings and radiographs, slipped capital femoral epiphysis is classified as pre-slip, acute, acute-on-chronic and chronic. The long-term outcome of slipped capital femoral epiphysis is directly related to severity and the presence or absence of avascular necrosis and/or chondrolysis. Therefore, the first priority in the treatment of slipped capital femoral epiphysis is to avoid complications while securing the epiphysis from further slippage. Medical treatment of patients with acute and acute-on-chronic slipped capital femoral epiphysis, as well as those presented in pre-slip stage, is the safest, although time-consuming. Manipulations, especially forced and repeated, are not recommended due to higher avascular necrosis risk. The use of intraoperative fluoroscopy to assist in the placement of internal fixation devices has markedly increased the success of surgical treatment. Controversy remains as to whether the proximal femoral epiphysis in severe, chronic slipped capital femoral epiphysis should be realigned by extracapsular osteotomies or just fixed in situ. The management protocol for slipped capital femoral epiphysis depends on the experience of the surgeon, motivation of the patient and technical facilities.

  1. Femoral neck fractures: A prospective assessment of the pattern ...

    OBJECTIVE: To review the pattern of femoral neck fractures, complications and outcome following fixation with Austin-Moore endoprosthesis. METHOD: A two year prospective study in patients who had fracture of the femoral neck based on strict inclusion criteria. All the patients were treated by Austin-Moore ...

  2. Femoral bifurcation with ipsilateral tibia hemimelia: Early outcome of ...

    Hereby, we present a case report of a 2-year-old boy who first presented in our orthopedic clinic as a 12-day-old neonate, with a grossly deformed right lower limb from a combination of complete tibia hemimelia and ipsilateral femoral bifurcation. Excision of femoral exostosis, knee disarticulation and prosthetic fitting gives ...

  3. Proximal Focal Femoral Deficiency in Ibadan a Developing ...

    The cultural aversion to amputation in our environment makes it difficult to employ that option of treatment. Proximal focal femoral deficiency in Ibadan a developing country's perspective and a review of the literature. Keywords: Proximal focal femoral deficiency , congenital malformations , limb malformations , lower limb ...

  4. [Treatment of femoral neck fracture--preference to internal fixation].

    Minato, Izumi

    2011-03-01

    In the guidelines for the treatment of femoral neck fracture, prosthetic replacement is recommended in displaced one and internal fixation is in undisplaced one. However, in the long view, survived femoral head after internal fixation can be superior to prosthesis which will deteriorate as time goes by. Surgical method should be considered not only by type of fracture but general status of the patient.

  5. Is the femoral cannulation for minimally invasive aortic valve replacement necessary?

    Cuenca, J; Rodriguez-Delgadillo, M A; Valle, J V; Campos, V; Herrera, J M; Rodriguez, F; Portela, F; Sorribas, F; Juffe, A

    1998-10-01

    Minimally invasive cardiac surgery through a small transverse sternotomy is a new promising technique that can be considered an alternative in most cases to aortic valve replacement thus reducing surgical trauma and subsequent time of hospitalization. The need to avoid the risks associated with femoro-femoral bypass has lead to the interest in aortic valve replacement (AVR) operations without femoral vessels cannulation. We want to emphasize a few important points of our technique, which differs somewhat from the one applied by Cosgrove and associates. This study details the approach to the minimally invasive AVR as first described by. Cosgrove et al. without standard femoral cannulation and points out our preliminary clinical experience. From October 1996 to May 1997 we have operated on 25 patients using minimally invasive AVR (MI-AVR) In 23 cases, access through transverse sternotomy as described by Cosgrove et al., was performed. In two additional cases the chest is opened via a mini-median sternotomy with an 'L'-shape extending from the sternal notch to the superior edge of the third interspace. Twenty-three patients underwent AVR through transverse sternotomy. The male/female ratio was 13:10. The mean age was 67 years (range 45-78 years). Seventy-four percent of the patients were over 65. Predominantly, in 43% of cases aortic valve stenosis and in 25% of cases aortic valve regurgitation isolated is presented. In 19 cases, a 10-cm transverse incision is performed over the second interspace. Likewise, in four cases over the third interspace according to the thorax morphology and length of the ascending aorta assessed by chest X-ray films. By convention, cannulation of the ascending aorta and right atrial appendage was performed as usual. In contrast, in one patient (5.5%), cannulation was placed in the superior vena cava and right common femoral vein into the inferior vena cava. In the present series, 15 mechanical prostheses and eight bioprostheses whose used

  6. Far infrared promotes wound healing through activation of Notch1 signaling.

    Hsu, Yung-Ho; Lin, Yuan-Feng; Chen, Cheng-Hsien; Chiu, Yu-Jhe; Chiu, Hui-Wen

    2017-11-01

    The Notch signaling pathway is critically involved in cell proliferation, differentiation, development, and homeostasis. Far infrared (FIR) has an effect that promotes wound healing. However, the underlying molecular mechanisms are unclear. In the present study, we employed in vivo and HaCaT (a human skin keratinocyte cell line) models to elucidate the role of Notch1 signaling in FIR-promoted wound healing. We found that FIR enhanced keratinocyte migration and proliferation. FIR induced the Notch1 signaling pathway in HaCaT cells and in a microarray dataset from the Gene Expression Omnibus database. We next determined the mRNA levels of NOTCH1 in paired normal and wound skin tissues derived from clinical patients using the microarray dataset and Ingenuity Pathway Analysis software. The result indicated that the Notch1/Twist1 axis plays important roles in wound healing and tissue repair. In addition, inhibiting Notch1 signaling decreased the FIR-enhanced proliferation and migration. In a full-thickness wound model in rats, the wounds healed more rapidly and the scar size was smaller in the FIR group than in the light group. Moreover, FIR could increase Notch1 and Delta1 in skin tissues. The activation of Notch1 signaling may be considered as a possible mechanism for the promoting effect of FIR on wound healing. FIR stimulates keratinocyte migration and proliferation. Notch1 in keratinocytes has an essential role in FIR-induced migration and proliferation. NOTCH1 promotes TWIST1-mediated gene expression to assist wound healing. FIR might promote skin wound healing in a rat model. FIR stimulates keratinocyte migration and proliferation. Notch1 in keratinocytes has an essential role in FIR-induced migration and proliferation. NOTCH1 promotes TWIST1-mediated gene expression to assist wound healing. FIR might promote skin wound healing in a rat model.

  7. Experience with the Notch Stress Approach for Fatigue Assessment of Welded Joints

    Pedersen, Mikkel Melters; Mouritsen, Ole Ø.; Hansen, Michael Rygaard

    2010-01-01

    In this paper, fatigue assessment using the notch stress approach is discussed based on re-analysis of many fatigue test results and experience from practical application. Three topics are treated; evaluation of the fatigue strength for as-welded details (FAT225) in the notch stress system......, problems regarding assessment of mild-SCF details and a novel proposal for extension of the notch stress approach for use with post-weld treated details....

  8. Active form Notch4 promotes the proliferation and differentiation of 3T3-L1 preadipocytes

    Lai, Peng-Yeh [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China); Tsai, Chong-Bin [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China); Department of Ophthalmology, Chiayi Christian Hospital, Chiayi 600, Taiwan, ROC (China); Tseng, Min-Jen, E-mail: biomjt@ccu.edu.tw [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China)

    2013-01-18

    Highlights: ► Notch4IC modulates the ERK pathway and cell cycle to promote 3T3-L1 proliferation. ► Notch4IC facilitates 3T3-L1 differentiation by up-regulating proadipogenic genes. ► Notch4IC promotes proliferation during the early stage of 3T3-L1 adipogenesis. ► Notch4IC enhances differentiation during subsequent stages of 3T3-L1 adipogenesis. -- Abstract: Adipose tissue is composed of adipocytes, which differentiate from precursor cells in a process called adipogenesis. Many signal molecules are involved in the transcriptional control of adipogenesis, including the Notch pathway. Previous adipogenic studies of Notch have focused on Notch1 and HES1; however, the role of other Notch receptors in adipogenesis remains unclear. Q-RT-PCR analyses showed that the augmentation of Notch4 expression during the differentiation of 3T3-L1 preadipocytes was comparable to that of Notch1. To elucidate the role of Notch4 in adipogenesis, the human active form Notch4 (N4IC) was transiently transfected into 3T3-L1 cells. The expression of HES1, Hey1, C/EBPδ and PPARγ was up-regulated, and the expression of Pref-1, an adipogenic inhibitor, was down-regulated. To further characterize the effect of N4IC in adipogenesis, stable cells expressing human N4IC were established. The expression of N4IC promoted proliferation and enhanced differentiation of 3T3-L1 cells compared with those of control cells. These data suggest that N4IC promoted proliferation through modulating the ERK pathway and the cell cycle during the early stage of 3T3-L1 adipogenesis and facilitated differentiation through up-regulating adipogenic genes such as C/EBPα, PPARγ, aP2, LPL and HSL during the middle and late stages of 3T3-L1 adipogenesis.

  9. Immunolocalization of notch signaling protein molecules in a maxillary chondrosarcoma and its recurrent tumor

    Siar CH

    2010-10-01

    Full Text Available Abstract Background Notch receptors are critical determinants of cell fate in a variety of organisms. Notch signaling is involved in the chondrogenic specification of neural crest cells. Aberrant Notch activity has been implicated in numerous human diseases including cancers; however its role in chondrogenic tumors has not been clarified. Method Tissue samples from a case of primary chondrosarcoma of the maxilla and its recurrent tumor were examined immunohistochemically for Notch1-4 and their ligands (Jagged1, Jagged2 and Delta1 expression. Results Both primary and recurrent tumors were histopathologically diagnosed as conventional hyaline chondrosarcoma (WHO Grade I. Hypercellular tumor areas strongly expressed Notch3 and Jagged1 in spindle and pleomorphic cells suggesting up-regulation of these protein molecules at sites of tumor proliferation. Expression patterns were distinct with some overlap. Differentiated malignant and atypical chondrocytes demonstrated variable expression levels of Jagged1, and weak to absent staining for Notch1, 4 and Delta1. Protein immunolocalization was largely membranous and cytoplasmic, sometimes outlining the lacunae of malignant chondrocytes. Hyaline cartilage demonstrated a diffuse or granular precipitation of Jagged1 suggesting presence of soluble Jagged1 activity at sites of abnormal chondrogenesis. No immunoreactivity for the other Notch members was observed. Calcified cartilage was consistently Notch-negative indicating down-regulation of Notch with cartilage maturation. Stromal components namely endothelial cells and fibroblasts variably expressed Notch1, 3 and Jagged1 but were mildly or non-reactive for the other members. Conclusions Results indicate that Notch signaling pathway may participate in cellular differentiation and proliferation in chondrosarcoma. Findings implicate Notch3 and Jagged1 as key molecules that influence the differentiation and maturation of cells of chondrogenic lineage.

  10. Inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer

    Zhao Li; Ma Yongjie; Gu Feng; Fu Li

    2014-01-01

    Background Paclitaxel (PAC) is the first-line chemotherapy drug for most breast cancer patients,but clinical studies showed that some breast cancer patients were insensitive to PAC,which led to chemotherapy failure.It was reported that Notch1 signaling participated in drug resistance of breast cancer.Here,we show whether Notch1 expression is related to PAC sensitivity of breast cancer.Methods We employed Notch1 siRNA and Notch1 inhibitor,N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester (DAPT),to down regulate Notch1 expression in human breast cancer cells MDA-MB-231,and detected the inhibition effect by Western blotting and reverse trans cription-polymerase chain reaction,respectively.After 24 hours exposure to different concentration of PAC (0,1,5,10,15,20,and 25 μg/ml),the viability of the control group and experimental group cells was tested by MTT.We also examined the expression of Notch1 in PAC sensitive and nonsensitive breast cancer patients,respectively by immunohistochemistry (IHC).The PAC sensitivity of breast cancer patients were identified by collagen gel droplet embedded culture-drug sensitivity test (CD-DST).Results Down regulation of Notch1 expression by Notch1siRNA interference or Notch1 inhibitor increased the PAC sensitivity in MDA-MB-231 cells (P <0.05).Also,the expression of Notch1 in PAC sensitive patients was much lower than that of PAC non-sensitive patients (P <0.01).Conclusion Notch1 expression has an effect on PAC sensitivity in breast cancer patients,and the inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer.

  11. The Notch Signaling Pathway Is Balancing Type 1 Innate Lymphoid Cell Immune Functions

    Thibaut Perchet

    2018-06-01

    Full Text Available The Notch pathway is one of the canonical signaling pathways implicated in the development of various solid tumors. During carcinogenesis, the Notch pathway dysregulation induces tumor expression of Notch receptor ligands participating to escape the immune surveillance. The Notch pathway conditions both the development and the functional regulation of lymphoid subsets. Its importance on T cell subset polarization has been documented contrary to its action on innate lymphoid cells (ILC. We aim to analyze the effect of the Notch pathway on type 1 ILC polarization and functions after disruption of the RBPJk-dependent Notch signaling cascade. Indeed, type 1 ILC comprises conventional NK (cNK cells and type 1 helper innate lymphoid cells (ILC1 that share Notch-related functional characteristics such as the IFNg secretion downstream of T-bet expression. cNK cells have strong antitumor properties. However, data are controversial concerning ILC1 functions during carcinogenesis with models showing antitumoral capacities and others reporting ILC1 inability to control tumor growth. Using various mouse models of Notch signaling pathway depletion, we analyze the effects of its absence on type 1 ILC differentiation and cytotoxic functions. We also provide clues into its role in the maintenance of immune homeostasis in tissues. We show that modulating the Notch pathway is not only acting on tumor-specific T cell activity but also on ILC immune subset functions. Hence, our study uncovers the intrinsic Notch signaling pathway in ILC1/cNK populations and their response in case of abnormal Notch ligand expression. This study help evaluating the possible side effects mediated by immune cells different from T cells, in case of multivalent forms of the Notch receptor ligand delta 1 treatments. In definitive, it should help determining the best novel combination of therapeutic strategies in case of solid tumors.

  12. Magnetic resonance imaging of the femoral head necrosis

    Narita, Shinya; Asada, Kanji; Yoshida, Kenjiro and others

    1986-06-01

    Ten patients with avascular femoral head necrosis and four normal adults were examined by magnetic resonance imaging (MRI). In addition, the relationship between MRI and pathophysiology of three operated-on avascular femoral heads was evaluated. The medullary cavities of the normal femoral heads had a strong signal intensity on the saturation recovery (SR) image due to fat marrow, and the T/sub 1/ relaxation time was 160 +- 11 msec. In avascular femoral head necrosis, the necrotic area had a low signal intensity on the SR image and a prolonged T/sub 1/ relaxation time, while the reactive fibrous area had more prolonged T/sub 1/ relaxation time. For these reasons, MRI was found to show the pathological changes of avascular femoral head necrosis and can be expected to be useful for making early diagnoses and operation planning.

  13. Magnetic resonance imaging of the femoral head necrosis

    Narita, Shinya; Asada, Kanji; Yoshida, Kenjiro

    1986-01-01

    Ten patients with avascular femoral head necrosis and four normal adults were examined by magnetic resonance imaging (MRI). In addition, the relationship between MRI and pathophysiology of three operated-on avascular femoral heads was evaluated. The medullary cavities of the normal femoral heads had a strong signal intensity on the saturation recovery (SR) image due to fat marrow, and the T 1 relaxation time was 160 ± 11 msec. In avascular femoral head necrosis, the necrotic area had a low signal intensity on the SR image and a prolonged T 1 relaxation time, while the reactive fibrous area had more prolonged T 1 relaxation time. For these reasons, MRI was found to show the pathological changes of avascular femoral head necrosis and can be expected to be useful for making early diagnoses and operation planning. (author)

  14. Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway

    Ma, Lijie; Dong, Pingping; Liu, Longzi; Gao, Qiang; Duan, Meng; Zhang, Si; Chen, She; Xue, Ruyi; Wang, Xiaoying

    2016-01-01

    Aberrant activation of Notch signaling frequently occurs in liver cancer, and is associated with liver malignancies. However, the mechanisms regulating pathologic Notch activation in hepatocellular carcinoma (HCC) remain unclear. Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. In the present study, we detected the expression of Pofut1 in 8 HCC cell lines and 253 human HCC tissues. We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. The in vitro assay demonstrated that Pofut1 overexpression accelerated the cell proliferation and migration in HCC cells. Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. - Highlights: • Pofut1 overexpression in HCC was correlated with aggressive tumor behaviors. • Pofut1 overexpression in HCC was associated with poor prognosis. • Pofut1 promoted cell proliferation, migration and invasion in hepatoma cells. • Pofut1 activated Notch signaling pathway in hepatoma cells.

  15. hCLP46 regulates U937 cell proliferation via Notch signaling pathway

    Ma, Wenzhan; Du, Jie; Chu, Qiaoyun [College of Life Science, Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Wang, Youxin [School of Public Health and Family Medicine, Capital Medical University, Beijing 100069 (China); Liu, Lixin [College of Life Science, Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Song, Manshu [School of Public Health and Family Medicine, Capital Medical University, Beijing 100069 (China); Wang, Wei, E-mail: wei6014@yahoo.com [College of Life Science, Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); School of Public Health and Family Medicine, Capital Medical University, Beijing 100069 (China)

    2011-04-29

    Highlights: {yields} Knock down of hCLP46 by RNAi impairs mammalian Notch signaling. {yields} hCLP46 affects neither cell surface Notch1 expression nor ligand-receptor binding. {yields} Knock down of hCLP46 inhibits U937 cell-growth by up-regulation of CDKN1B. -- Abstract: Human CAP10-like protein 46 kDa (hCLP46) is the homolog of Rumi, which is the first identified protein O-glucosyltransferase that modifies Notch receptor in Drosophila. Dysregulation of hCLP46 occurs in many hematologic diseases, but the role of hCLP46 remains unclear. Knockdown of hCLP46 by RNA interference resulted in decreased protein levels of endogenous Notch1, Notch intracellular domain (NICD) and Notch target gene Hes-1, suggesting the impairment of the Notch signaling. However, neither cell surface Notch expression nor ligand binding activities were affected. In addition, down-regulated expression of hCLP46 inhibited the proliferation of U937 cells, which was correlated with increased cyclin-dependent kinase inhibitor (CDKI) CDKN1B (p27) and decreased phosphorylation of retinoblastoma (RB) protein. We showed that lack of hCLP46 results in impaired ligand induced Notch activation in mammalian cell, and hCLP46 regulates the proliferation of U937 cell through CDKI-RB signaling pathway, which may be important for the pathogenesis of leukemia.

  16. Characterization and analysis of surface notches on Ti-alloy plates fabricated by additive manufacturing techniques

    Chan, Kwai S.

    2015-01-01

    Rectangular plates of Ti–6Al–4V with extra low interstitial (ELI) were fabricated by layer-by-layer deposition techniques that included electron beam melting (EBM) and laser beam melting (LBM). The surface conditions of these plates were characterized using x-ray micro-computed tomography. The depth and radius of surface notch-like features on the LBM and EBM plates were measured from sectional images of individual virtual slices of the rectangular plates. The stress concentration factors of individual surface notches were computed and analyzed statistically to determine the appropriate distributions for the notch depth, notch radius, and stress concentration factor. These results were correlated with the fatigue life of the Ti–6Al–4V ELI alloys from an earlier investigation. A surface notch analysis was performed to assess the debit in the fatigue strength due to the surface notches. The assessment revealed that the fatigue lives of the additively manufactured plates with rough surface topographies and notch-like features are dominated by the fatigue crack growth of large cracks for both the LBM and EBM materials. The fatigue strength reduction due to the surface notches can be as large as 60%–75%. It is concluded that for better fatigue performance, the surface notches on EBM and LBM materials need to be removed by machining and the surface roughness be improved to a surface finish of about 1 μm. (paper)

  17. Characterization and analysis of surface notches on Ti-alloy plates fabricated by additive manufacturing techniques

    Chan, Kwai S.

    2015-12-01

    Rectangular plates of Ti-6Al-4V with extra low interstitial (ELI) were fabricated by layer-by-layer deposition techniques that included electron beam melting (EBM) and laser beam melting (LBM). The surface conditions of these plates were characterized using x-ray micro-computed tomography. The depth and radius of surface notch-like features on the LBM and EBM plates were measured from sectional images of individual virtual slices of the rectangular plates. The stress concentration factors of individual surface notches were computed and analyzed statistically to determine the appropriate distributions for the notch depth, notch radius, and stress concentration factor. These results were correlated with the fatigue life of the Ti-6Al-4V ELI alloys from an earlier investigation. A surface notch analysis was performed to assess the debit in the fatigue strength due to the surface notches. The assessment revealed that the fatigue lives of the additively manufactured plates with rough surface topographies and notch-like features are dominated by the fatigue crack growth of large cracks for both the LBM and EBM materials. The fatigue strength reduction due to the surface notches can be as large as 60%-75%. It is concluded that for better fatigue performance, the surface notches on EBM and LBM materials need to be removed by machining and the surface roughness be improved to a surface finish of about 1 μm.

  18. Prediction of multiaxial fatigue life for notched specimens of titanium alloy TC4

    Wu, Z. R.; Li, Z. X. [Southeast University, Nanjing (China); Hu, X. T.; Song, Y. D. [Nanjing University, Nanjing (China)

    2016-05-15

    Both the proportional and nonproportional multiaxial fatigue tests were conducted on two kinds of notched specimens of titanium alloy TC4. The multiaxial fatigue critical area of notched specimen is considered as the location experiencing the maximum damage. It is unsatisfactory to predict the multiaxial fatigue life with the local stress and strain in the fatigue critical area. The critical distance concepts are employed in the multiaxial life prediction method for notched specimens. The proposed method was checked by the test data of TC4 notched specimens. The prediction results are almost within a factor of three scatter band of the test results.

  19. The effect of electric discharge machined notches on the fracture toughness of several structural alloys

    Joyce, J.A.; Link, R.E.

    1993-09-01

    Recent computational studies of the stress and strain fields at the tip of very sharp notches have shown that the stress and strain fields are very weakly dependent on the initial geometry of the notch once the notch has been blunted to a radius that is 6 to 10 times the initial root radius. It follows that if the fracture toughness of a material is sufficiently high so that fracture initiation does not occur in a specimen until the crack-tip opening displacement (CTOD) reaches a value from 6 to 10 times the size of the initial notch tip diameter, then the fracture toughness will be independent of whether a fatigue crack or a machined notch served as the initial crack. In this experimental program the fracture toughness (J Ic and J resistance (J-R) curve, and CTOD) for several structure alloys was measured using specimens with conventional fatigue cracks and with EDM machined notches. The results of this program have shown, in fact, that most structural materials do not achieve initiation CTOD values on the order of 6 to 10 times the radius of even the smallest EDM notch tip presently achievable. It is found furthermore that tougher materials do not seem to be less dependent on the type of notch tip present. Some materials are shown to be much more dependent on the type of notch tip used, but no simple pattern is found that relates this observed dependence to the material strength toughness, or strain hardening rate

  20. Spoof surface plasmon polaritons based notch filter for ultra-wideband microwave waveguide

    Xiao, Binggang; Li, Sheng-Hua; Xiao, Sanshui

    2016-01-01

    Spoof surface plasmon polaritons based notch filter for ultra-wideband microwave waveguide is proposed. Owing to subwavelength confinement, such a filter has advantage in the structure size without sacrificing the performance. The spoof SPP based notch is introduced to suppress the WLAN and satel......Spoof surface plasmon polaritons based notch filter for ultra-wideband microwave waveguide is proposed. Owing to subwavelength confinement, such a filter has advantage in the structure size without sacrificing the performance. The spoof SPP based notch is introduced to suppress the WLAN...

  1. Notch Signaling Mediates Skeletal Muscle Atrophy in Cancer Cachexia Caused by Osteosarcoma

    Xiaodong Mu

    2016-01-01

    Full Text Available Skeletal muscle atrophy in cancer cachexia is mediated by the interaction between muscle stem cells and various tumor factors. Although Notch signaling has been known as a key regulator of both cancer development and muscle stem cell activity, the potential involvement of Notch signaling in cancer cachexia and concomitant muscle atrophy has yet to be elucidated. The murine K7M2 osteosarcoma cell line was used to generate an orthotopic model of sarcoma-associated cachexia, and the role of Notch signaling was evaluated. Skeletal muscle atrophy was observed in the sarcoma-bearing mice, and Notch signaling was highly active in both tumor tissues and the atrophic skeletal muscles. Systemic inhibition of Notch signaling reduced muscle atrophy. In vitro coculture of osteosarcoma cells with muscle-derived stem cells (MDSCs isolated from normal mice resulted in decreased myogenic potential of MDSCs, while the application of Notch inhibitor was able to rescue this repressed myogenic potential. We further observed that Notch-activating factors reside in the exosomes of osteosarcoma cells, which activate Notch signaling in MDSCs and subsequently repress myogenesis. Our results revealed that signaling between tumor and muscle via the Notch pathway may play an important role in mediating the skeletal muscle atrophy seen in cancer cachexia.

  2. Notch2 Signaling Maintains NSC Quiescence in the Murine Ventricular-Subventricular Zone

    Anna Engler

    2018-01-01

    Full Text Available Neurogenesis continues in the ventricular-subventricular zone (V-SVZ of the adult forebrain from quiescent neural stem cells (NSCs. V-SVZ NSCs are a reservoir for new olfactory bulb (OB neurons that migrate through the rostral migratory stream (RMS. To generate neurons, V-SVZ NSCs need to activate and enter the cell cycle. The mechanisms underlying NSC transition from quiescence to activity are poorly understood. We show that Notch2, but not Notch1, signaling conveys quiescence to V-SVZ NSCs by repressing cell-cycle-related genes and neurogenesis. Loss of Notch2 activates quiescent NSCs, which proliferate and generate new neurons of the OB lineage. Notch2 deficiency results in accelerated V-SVZ NSC exhaustion and an aging-like phenotype. Simultaneous loss of Notch1 and Notch2 resembled the total loss of Rbpj-mediated canonical Notch signaling; thus, Notch2 functions are not compensated in NSCs, and Notch2 is indispensable for the maintenance of NSC quiescence in the adult V-SVZ.

  3. Plane-stress fields for sharp notches in pressure-sensitive materials

    Al-Abduljabbar, Abdulhamid

    2003-01-01

    The effect of pressure sensitive yield on materials toughness can be determined by investigating stress fields around cracks and notches. In this work, fully-developed plastic stress fields around sharp wedge-shaped notches of perfectly-plastic pressure-sensitive materials are investigated for plane-stress case and Mode 1 loading condition. The pressure-sensitive yielding behavior is represented using the Drucker-Prager criterion. Using equilibrium equations, boundary conditions, and the yield criterion, closed-form expressions for stress fields are derived. The analysis covers the gradual change in the notch angle and compares it with the limiting case of a pure horizontal crack. Effects of notch geometry and pressure sensitivity on stress fields are examined by considering different specimen geometries, as well as different levels of pressure sensitivity. Results indicate that while the stress values directly ahead of the notch-tip are not affected, the extent of stress sector at notch front is reduced, thereby causing increase in the radial stress value around the notch. As the pressure sensitivity increases the reduction of the stress sector directly ahead of the notch tip is more evident. Also, for high pressure sensitivity values, introduction of the notch angle reduces the variation of the stress levels. Results are useful for design of structural components. (author)

  4. Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway

    Ma, Lijie [Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai (China); Dong, Pingping [Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai (China); Liu, Longzi; Gao, Qiang; Duan, Meng [Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai (China); Zhang, Si; Chen, She [Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai (China); Xue, Ruyi, E-mail: xue.ruyi@zs-hospital.sh.cn [Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai (China); Wang, Xiaoying, E-mail: xiaoyingwang@fudan.edu.cn [Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai (China)

    2016-04-29

    Aberrant activation of Notch signaling frequently occurs in liver cancer, and is associated with liver malignancies. However, the mechanisms regulating pathologic Notch activation in hepatocellular carcinoma (HCC) remain unclear. Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. In the present study, we detected the expression of Pofut1 in 8 HCC cell lines and 253 human HCC tissues. We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. The in vitro assay demonstrated that Pofut1 overexpression accelerated the cell proliferation and migration in HCC cells. Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. - Highlights: • Pofut1 overexpression in HCC was correlated with aggressive tumor behaviors. • Pofut1 overexpression in HCC was associated with poor prognosis. • Pofut1 promoted cell proliferation, migration and invasion in hepatoma cells. • Pofut1 activated Notch signaling pathway in hepatoma cells.

  5. Outcomes of trochanteric femoral fractures treated with proximal femoral nail: an analysis of 100 consecutive cases

    Korkmaz MF

    2014-04-01

    Full Text Available Mehmet Fatih Korkmaz,1 Mehmet Nuri Erdem,2 Zeliha Disli,3 Engin Burak Selcuk,4 Mustafa Karakaplan,1 Abdullah Gogus5 1Department of Orthopedics and Traumatology, Inonu University School of Medicine, Malatya, Turkey; 2Department of Orthopedics and Traumatology, Nisantasi University School of Medicine, Istanbul, Turkey; 3Department of Anesthesiology, Malatya Government Hospital, Malatya, Turkey; 4Department of Family Medicine, Inonu University School of Medicine, Malatya, Turkey; 5Department of Orthopedics and Traumatology, Florence Nightingale Hospital, Istanbul, Turkey Purpose: In this study, we aimed to report the results of a retrospective study carried out at our institute regarding cases of patients who had suffered proximal femoral fractures between January 2002 and February 2007, and who were treated with a proximal femoral nail. Materials and methods: One hundred consecutive cases were included in the study. A case documentation form was used to obtain intraoperative data including age, sex, mechanism of injury, type of fracture according to Association for Osteosynthesis/Association for the Study of Internal Fixation (AO/ASIF classification and the American Society of Anesthesiologists' (ASA physical status classification (ASA grade. Clinical and radiographic examinations were performed at the time of admission and at the 6th week; subsequent visits were organized on the 3rd month, 6th month, and 12th month, and in patients with longer follow-up and annually postoperatively. The Harris score of hip function was used, and any change in the position of the implants and the progress of the fracture union, which was determined radiologically, was noted. Results: The mean age of the patients was 77.66 years (range: 37–98 years, and the sex distribution was 32 males and 68 females. Seventy-three fractures were reduced by closed means, whereas 27 needed limited open reduction. The mean follow-up time for the study group was 31.3 months (range

  6. Outcomes of trochanteric femoral fractures treated with proximal femoral nail: an analysis of 100 consecutive cases.

    Korkmaz, Mehmet Fatih; Erdem, Mehmet Nuri; Disli, Zeliha; Selcuk, Engin Burak; Karakaplan, Mustafa; Gogus, Abdullah

    2014-01-01

    In this study, we aimed to report the results of a retrospective study carried out at our institute regarding cases of patients who had suffered proximal femoral fractures between January 2002 and February 2007, and who were treated with a proximal femoral nail. One hundred consecutive cases were included in the study. A case documentation form was used to obtain intraoperative data including age, sex, mechanism of injury, type of fracture according to Association for Osteosynthesis/Association for the Study of Internal Fixation (AO/ASIF) classification and the American Society of Anesthesiologists' (ASA) physical status classification (ASA grade). Clinical and radiographic examinations were performed at the time of admission and at the 6th week; subsequent visits were organized on the 3rd month, 6th month, and 12th month, and in patients with longer follow-up and annually postoperatively. The Harris score of hip function was used, and any change in the position of the implants and the progress of the fracture union, which was determined radiologically, was noted. The mean age of the patients was 77.66 years (range: 37-98 years), and the sex distribution was 32 males and 68 females. Seventy-three fractures were reduced by closed means, whereas 27 needed limited open reduction. The mean follow-up time for the study group was 31.3 months (range: 12-75 months). Postoperative radiographs showed a near-anatomical fracture reduction in 78% of patients. The Harris hip score was negatively correlated with the ASA score and patient age. No cases of implant failure were observed. Three patients died before discharge (one due to pulmonary embolism, two due to cardiac arrest), and five patients died due to unrelated medical conditions within the first 3 months of the follow-up. Our study showed that proximal femoral nail is a reliable fixation with good fracture union, and it is not associated with major complications in any type of trochanteric femoral fracture.

  7. Avascular necrosis of the femoral head after osteosynthesis of femoral neck fracture.

    Min, Byung-Woo; Kim, Sung-Jin

    2011-05-18

    The reported incidence of avascular necrosis after femoral neck fracture fixation varies widely, and there is no consensus regarding its risk factors. We evaluated the incidence of avascular necrosis of the femoral head with the use of contemporary techniques for femoral neck fracture fixation. We then sought to determine what potential risk factors influenced the development of avascular necrosis.Between 1990 and 2005, one hundred sixty-three intracapsular femoral neck fractures in 163 patients were treated with internal fixation at our level-I trauma center. All patients were monitored until conversion to total hip arthroplasty or for a minimum of 2 years postoperatively. Ten patients (10 hips) died and 7 patients (7 hips) were lost to follow-up. The remaining 146 patients (146 hips) had a mean 5.2 years of follow-up (range, 3 months to 17 years). The incidence of avascular necrosis was 25.3% (37 hips). The average time to diagnosis of avascular necrosis was 18.8 months (range, 3-47 months). Patient sex, age, interval from injury to surgery, and mechanism of injury were statistically not associated with the development of avascular necrosis. The quality of fracture reduction, adequacy of fixation, degree of displacement, and comminution of the posterior cortex were significantly associated. After we controlled for patient and radiographic characteristics, multivariate analyses indicated that the important predictors for avascular necrosis are poor reduction (odds ratio=13.889) and initial displacement of the fracture (odds ratio=4.693). Copyright 2011, SLACK Incorporated.

  8. Analysis of slipped capital femoral epiphysis

    Magid, D.; Fishman, E.K.; Sponseller, P.D.; Griffin, P.P.

    1988-01-01

    CT with multiplanar reconstruction (CT/MPR) was used to assess 25 adolescents with known or suspected slipped capital femoral epiphysis (SCFE). CT/MPR localizes the epiphysis in three planes, establishing its relationship to the acetabulum and the metaphyseal neck. MPR facilitates measurements of head-neck angles, residusal head-neck contact, and relative retrovision. CT/MPR may establish the true age of the epiphyseal failure and can reveal subtle SCFE in the face of normal plain films. Patients often present with confusing histories; clues to the true age of failure include subtle signs of healing, remodeling, or new bone buttressing. Characterization of acute versus chronic conditions influences preoperative planning. Postoperatively, CT/MPR confirms early results and follows epiphyseal fusion and remodelling. It also detects complications, such as pin or graft migration avascular necrosis (AVN), or chondrolysis

  9. TLX1 and NOTCH coregulate transcription in T cell acute lymphoblastic leukemia cells

    Lee Norman H

    2010-07-01

    Full Text Available Abstract Background The homeobox gene TLX1 (for T-cell leukemia homeobox 1, previously known as HOX11 is inappropriately expressed in a major subgroup of T cell acute lymphoblastic leukemia (T-ALL where it is strongly associated with activating NOTCH1 mutations. Despite the recognition that these genetic lesions cooperate in leukemogenesis, there have been no mechanistic studies addressing how TLX1 and NOTCH1 functionally interact to promote the leukemic phenotype. Results Global gene expression profiling after downregulation of TLX1 and inhibition of the NOTCH pathway in ALL-SIL cells revealed that TLX1 synergistically regulated more than 60% of the NOTCH-responsive genes. Structure-function analysis demonstrated that TLX1 binding to Groucho-related TLE corepressors was necessary for maximal transcriptional regulation of the NOTCH-responsive genes tested, implicating TLX1 modulation of the NOTCH-TLE regulatory network. Comparison of the dataset to publicly available biological databases indicated that the TLX1/NOTCH-coregulated genes are frequently targeted by MYC. Gain- and loss-of-function experiments confirmed that MYC was an essential mediator of TLX1/NOTCH transcriptional output and growth promotion in ALL-SIL cells, with TLX1 contributing to the NOTCH-MYC regulatory axis by posttranscriptional enhancement of MYC protein levels. Functional classification of the TLX1/NOTCH-coregulated targets also showed enrichment for genes associated with other human cancers as well as those involved in developmental processes. In particular, we found that TLX1, NOTCH and MYC coregulate CD1B and RAG1, characteristic markers of early cortical thymocytes, and that concerted downregulation of the TLX1 and NOTCH pathways resulted in their irreversible repression. Conclusions We found that TLX1 and NOTCH synergistically regulate transcription in T-ALL, at least in part via the sharing of a TLE corepressor and by augmenting expression of MYC. We conclude that

  10. PI3K/AKT signaling inhibits NOTCH1 lysosome-mediated degradation.

    Platonova, Natalia; Manzo, Teresa; Mirandola, Leonardo; Colombo, Michela; Calzavara, Elisabetta; Vigolo, Emilia; Cermisoni, Greta Chiara; De Simone, Daria; Garavelli, Silvia; Cecchinato, Valentina; Lazzari, Elisa; Neri, Antonino; Chiaramonte, Raffaella

    2015-06-06

    The pathways of NOTCH and PI3K/AKT are dysregulated in about 60% and 48% of T-cell acute lymphoblastic leukemia (T-ALL) patients, respectively. In this context, they interact and cooperate in controlling tumor cell biology. Here, we propose a novel mechanism by which the PI3K/AKT pathway regulates NOTCH1 in T-ALL, starting from the evidence that the inhibition of PI3K/AKT signaling induced by treatment with LY294002 or transient transfection with a dominant negative AKT mutant downregulates NOTCH1 protein levels and activity, without affecting NOTCH1 transcription. We showed that the withdrawal of PI3K/AKT signaling was associated to NOTCH1 phosphorylation in tyrosine residues and monoubiquitination of NOTCH1 detected by Ubiquitin capture assay. Co-immunoprecipitation assay and colocalization analysis further showed that the E3 ubiquitin ligase c-Cbl interacts and monoubiquitinates NOTCH1, activating its lysosomal degradation. These results suggest that the degradation of NOTCH1 could represent a mechanism of control by which NOTCH1 receptors are actively removed from the cell surface. This mechanism is finely regulated by the PI3K/AKT pathway in physiological conditions. In pathological conditions characterized by PI3K/AKT hyperactivation, such as T-ALL, the excessive AKT signaling could lead to NOTCH1 signaling dysregulation. Therefore, a therapeutic strategy directed to PI3K/AKT in T-ALL could contemporaneously inhibit the dysregulated NOTCH1 signaling. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  11. Glioma cell fate decisions mediated by Dll1-Jag1-Fringe in Notch1 signaling pathway.

    Shi, Xiaofei; Wang, Ruiqi

    2017-09-21

    The Notch family of proteins plays a vital role in determining cell fates, such as proliferation, differentiation, and apoptosis. It has been shown that Notch1 and its ligands, Dll1 and Jag1, are overexpressed in many glioma cell lines and primary human gliomas. The roles of Notch1 in some cancers have been firmly established, and recent data implicate that it plays important roles in glioma cell fate decisions. This paper focuses on devising a specific theoretical framework that incorporates Dll1, Jag1, and Fringe in Notch1 signaling pathway to explore their functional roles of these proteins in glioma cells in the tumorigenesis and progression of human gliomas, and to study how glioma cell fate decisions are modulated by both trans-activation and cis-inhibition. This paper presents a computational model for Notch1 signaling pathway in glioma cells. Based on the bifurcation analysis of the model, we show that how the glioma cell fate decisions are modulated by both trans-activation and cis-inhibition mediated by the Fringe protein, providing insight into the design and control principles of the Notch signaling system and the gliomas. This paper presents a computational model for Notch1 signaling pathway in glioma cells based on intertwined dynamics with cis-inhibition and trans-activation involving the proteins Notch1, Dll1, Jag1, and Fringe. The results show that how the glioma cell fate transitions are performed by the Notch1 signaling. Transition from grade III ∼ IV with significantly high Notch1 to grade I ∼ II with high Notch1, and then to normal cells by repressing the Fringe levels or decreasing the strength of enhancement induced by Fringe.

  12. Droplet digital PCR analysis of NOTCH1 gene mutations in chronic lymphocytic leukemia.

    Minervini, Angela; Francesco Minervini, Crescenzio; Anelli, Luisa; Zagaria, Antonella; Casieri, Paola; Coccaro, Nicoletta; Cumbo, Cosimo; Tota, Giuseppina; Impera, Luciana; Orsini, Paola; Brunetti, Claudia; Giordano, Annamaria; Specchia, Giorgina; Albano, Francesco

    2016-12-27

    In chronic lymphocytic leukemia (CLL), NOTCH1 gene mutations (NOTCH1mut) have been associated with adverse prognostic features but the independence of these as a prognostic factor is still controversial. In our study we validated a c.7541-7542delCT NOTCH1 mutation assay based on droplet digital PCR (ddPCR); we also analyzed the NOTCH1mut allelic burden, expressed as fractional abundance (FA), in 88 CLL patients at diagnosis to assess its prognostic role and made a longitudinal ddPCR analysis in 10 cases harboring NOTCH1mut to verify the FA variation over time. Our data revealed that with the ddPCR approach the incidence of NOTCH1mut in CLL was much higher (53.4%) than expected. However, longitudinal ddPCR analysis of CLL cases showed a statistically significant reduction of the NOTCH1mut FA detected at diagnosis after treatment (median FA 11.67 % vs 0.09 %, respectively, p = 0.01); the same difference, in terms of NOTCH1mut FA, was observed in the relapsed cases compared to the NOTCH1mut allelic fraction observed in patients in complete or partial remission (median FA 4.75% vs 0.43%, respectively, p = 0.007). Our study demonstrated a much higher incidence of NOTCH1mut in CLL than has previously been reported, and showed that the NOTCH1mut allelic burden evaluation by ddPCR might identify patients in need of a closer clinical follow-up during the "watch and wait" interval and after standard chemotherapy.

  13. Dll1- and Dll4-mediated Notch signaling is required for homeostasis of intestinal stem cells

    Pellegrinet, Luca; Rodilla, Veronica; Liu, Zhenyi; Chen, Shuang; Koch, Ute; Espinosa, Lluis; Kaestner, Klaus H.; Kopan, Raphael; Lewis, Julian; Radtke, Freddy

    2011-01-01

    Background & Aims Ablation of Notch signaling within the intestinal epithelium results in loss of proliferating crypt progenitors, due to their conversion into post-mitotic secretory cells. We aimed to confirm that Notch was active in stem cells (SC), investigate consequences of loss of Notch signaling within the intestinal SC compartment, and identify the physiological ligands of Notch in mouse intestine. Furthermore, we investigated whether the induction of goblet cell differentiation that results from loss of Notch requires the transcription factor Krüppel-like factor 4 (Klf4). Methods Trasgenic mice that carried a reporter of Notch1 activation were used for lineage tracing experiments. The in vivo functions of the Notch ligands Jagged1 (Jag1), Delta-like1 (Dll1), Delta-like4 (Dll4), and the transcription factor Klf4 were assessed in mice with inducible, gut-specific gene targeting (Vil-Cre-ERT2). Results Notch1 signaling was found to be activated in intestinal SC. Although deletion of Jag1 or Dll4 did not perturb the intestinal epithelium, inactivation of Dll1 resulted in a moderate increase in number of goblet cells without noticeable effects of progenitor proliferation. However, simultaneous inactivation of Dll1 and Dll4 resulted in the complete conversion of proliferating progenitors into post-mitotic goblet cells, concomitant with loss of SC (Olfm4+, Lgr5+ and Ascl2+). Klf4 inactivation did not interfere with goblet cell differentiation in adult wild-type or in Notch pathway-deficient gut. Conclusions Notch signaling in SC and progenitors is activated by Dll1 and Dll4 ligands and is required for maintenance of intestinal progenitor and SC. Klf4 is dispensable for goblet cell differentiation in intestines of adult Notch-deficient mice. PMID:21238454

  14. Dll1- and dll4-mediated notch signaling are required for homeostasis of intestinal stem cells.

    Pellegrinet, Luca; Rodilla, Veronica; Liu, Zhenyi; Chen, Shuang; Koch, Ute; Espinosa, Lluis; Kaestner, Klaus H; Kopan, Raphael; Lewis, Julian; Radtke, Freddy

    2011-04-01

    Ablation of Notch signaling within the intestinal epithelium results in loss of proliferating crypt progenitors due to their conversion into postmitotic secretory cells. We aimed to confirm that Notch was active in stem cells (SCs), investigate consequences of loss of Notch signaling within the intestinal SC compartment, and identify the physiologic ligands of Notch in mouse intestine. Furthermore, we investigated whether the induction of goblet cell differentiation that results from loss of Notch requires the transcription factor Krüppel-like factor 4 (Klf4). Transgenic mice that carried a reporter of Notch1 activation were used for lineage tracing experiments. The in vivo functions of the Notch ligands Jagged1 (Jag1), Delta-like1 (Dll1), Delta-like4 (Dll4), and the transcription factor Klf4 were assessed in mice with inducible, gut-specific gene targeting (Vil-Cre-ER(T2)). Notch1 signaling was found to be activated in intestinal SCs. Although deletion of Jag1 or Dll4 did not perturb the intestinal epithelium, inactivation of Dll1 resulted in a moderate increase in number of goblet cells without noticeable effects of progenitor proliferation. However, simultaneous inactivation of Dll1 and Dll4 resulted in the complete conversion of proliferating progenitors into postmitotic goblet cells, concomitant with loss of SCs (Olfm4(+), Lgr5(+), and Ascl2(+)). Klf4 inactivation did not interfere with goblet cell differentiation in adult wild-type or in Notch pathway-deficient gut. Notch signaling in SCs and progenitors is activated by Dll1 and Dll4 ligands and is required for maintenance of intestinal progenitor and SCs. Klf4 is dispensable for goblet cell differentiation in intestines of adult Notch-deficient mice. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  15. Femoral neck buttressing: a radiographic and histologic analysis

    Dixon, T.; Benjamin, J.; Lund, P.; Graham, A.; Krupinski, E.

    2000-01-01

    Objective. To examine the incidence, radiographic and histologic findings of medial femoral neck buttressing in a consecutive group of patients undergoing total hip arthroplasty.Design. Biomechanical parameters were evaluated on standard anteroposterior pelvic radiographs of 113 patients prior to hip replacement surgery. Demographic information on all patients was reviewed and histologic evaluation was performed on specimens obtained at the time of surgery.Results. The incidence of medial femoral neck buttressing was found to be 50% in a consecutive series of patients undergoing total hip arthroplasty. The incidence was slightly higher in women (56% vs 41%). Patients with buttressing had increased neck-shaft angles and smaller femoral neck diameters than were seen in patients without buttressing. Histologic evaluation demonstrated that the buttress resulted from deposition bone by the periosteum on the femoral neck in the absence of any evidence of femoral neck fracture.Conclusion. It would appear that femoral neck buttressing occurs in response to increased joint reactive forces seen at the hip being transmitted through the femoral neck. The increased joint reactive force can be related to the increased neck shaft angle seen in patients with buttressing. (orig.)

  16. Clinical study on 44 cases of femoral hernia

    Yamamoto, Ryo; Shinozaki, Hiroharu; Kase, Kenichi; Kobayashi, Kenji; Sasaki, Junichi

    2012-01-01

    Femoral hernia is a surgical disease that is frequently associated with incarceration and necessitates emergency surgery. However, there are only a few studies referred which have compared emergency and elective surgery for femoral hernias. We retrospectively reviewed the clinical characteristics of patients diagnosed as having femoral hernia between 2005 and 2009 in our institution. The clinical features of emergency repairs were compared with those of elective ones, and diagnostic values of preoperative diagnostic modalities were studied. The mean age of the patients was 73±12 years. Females comprised 68% of the cases, and right femoral hernias comprised 70% of the cases. Incarceration was associated with 66% of the cases (29 patients), and emergency surgery was performed in 52% of the patients (23 patients). Bowel resection was performed in 32% of the cases (14 patients). The mean age, body temperature, white blood cell (WBC) count, and LDH value were higher in the emergency repairs than in the elective one, and most of the hernias were repaired with McVay's procedure. CT scans had a high diagnostic value in detecting femoral hernias (44%) and incarceration (88%). It was confirmed that femoral hernias were frequently associated with incarceration and CT scan has a high diagnostic value in femoral hernias. (author)

  17. Simultaneous avascular necrosis of both medial and lateral femoral condyles

    Mansberg, R.

    2002-01-01

    Full text: Avascular necrosis (AVN) of a femoral condyle is a common orthopaedic condition. While both medial and lateral femoral condyles may be involved either singly or sequentially the simultaneous occurrence of AVN of both femoral condyles is extremely uncommon. A 57-year-old male is presented who developed the onset of severe left sided knee pain suddenly at rest. Plain and tomographic radiography was unremarkable and a bone scan was performed. Markedly increased vascularity was demonstrated in the left knee with intense osteoblastic activity in the left medial and femoral condyles more marked in the lateral femoral condyle. A diagnosis of AVN of both femoral condyles was made and a MRI exam was performed to confirm this unusual diagnosis. The MRI showed a diffuse increase in intensity bilaterally with subtle bony change in the subarticular bone consistent with AVN more marked in the left lateral femoral condyle. The patients' symptoms resolved with supportive treatment. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  18. Ductile crack initiation in the Charpy V-notch test

    Server, W.L.; Norris, D.M. Jr.; Prado, M.E.

    1978-01-01

    Initiation and growth of a crack in the Charpy V-notch test was investigated by performing both static and impact controlled deflection tests. Test specimens were deformed to various deflections, heat-tinted to mark crack extension and broken apart at low temperature to allow extension measurements. Measurement of the crack extension provided an estimate of crack initiation as defined by different criteria. Crack initiation starts well before maximum load, and is dependent on the definition of ''initiation''. Using a definition of first micro-initiation away from the ductile blunting, computer model predictions agreed favorably with the experimental results

  19. Positioning of the femoral tunnel for arthroscopic reconstruction of the anterior cruciate ligament: comparative study of 2 techniques Posicionamento do túnel femoral na reconstrução artroscópica do LCA: estudo comparativo de duas técnicas

    Roberto Freire da Mota Albuquerque

    2007-01-01

    Full Text Available OBJECTIVE: To compare the accuracy of positioning of the femoral tunnel in reconstructing the anterior cruciate ligament by means of 2 techniques: tibial tunnel and anteromedial portal. METHOD: Femoral tunnels were drilled in 20 knees from human cadavers by means of arthroscopy. Group I had the femoral tunnel drilled via a trans-tibial tunnel, and Group II via the anteromedial portal. Four variables were measured: A posterior wall thickness; B tunnel positioning at the notch; C tunnel inclination in relation to the femoral axis; and D distance between the wire guide exit and the lateral epicondyle. RESULTS: As above, respectively, A 2.23 mm for group I and 2.36 mm for group II (P =.54; B 25.5° for group I and 30.0° for group II (P =.23; C 23.9° for group I and 32.0° for group II (P =.02; D 7.8 cm for group I and 3.9 cm for group II (P OBJETIVO: Comparar a acurácia do posicionamento do túnel femoral na reconstrução do ligamento cruzado anterior através de duas vias: túnel tibial e portal ântero - medial. MÉTODO: Foram perfurados túneis femorais em vinte joelhos de cadáveres humanos por via artroscópica. Grupo I: túnel femoral por acesso trans túnel tibial. Grupo II: via portal ântero-medial. Quatro variáveis foram estudadas: A espessura da parede posterior; B posicionamento do túnel no intercôndilo; C angulação do túnel em relação ao eixo do fêmur; D distância entre a saída do fio guia e o epicôndilo lateral. RESULTADO: A grupo I: 2,23 mm, grupo II: 2,36 mm (p=0,543; B grupo I: 25,5º, grupo II: 30º (p=0,226; C grupo I: 23,9º, grupo II: 32º (p= 0,014; D grupo I: 7,8 cm, grupo II 3,9 cm (p<0,001. CONCLUSÃO: As duas técnicas obteveram o posicionamento desejado da entrada do túnel femoral e espessura adequada da cortical posterior. A perfuração via portal ântero-medial pode propiciar maior proteção contra rotura da parede posterior.

  20. Treatment of the femoral neck peudoarthrosis in childhood: Case report

    Vukašinović Zoran

    2013-01-01

    Full Text Available Introduction. Femoral neck fractures in children and adolescents are rare. However, their complications are frequent - avascular necrosis, femoral neck pseudoarthrosis, premature physeal closure with consequent growth disturbance and coxa vara deformity. Case Outline. A 9.5­year­old boy was injured in a car accident, and femoral neck fracture was diagnosed. Prior to admission at our hospital he was surgically treated several times. He was admitted at our hospital eight months following the accident. On the X­ray transcervical pseudoarthrosis of the femoral neck was found, as well as coxa vara deformity and metaphyseal avascular necrosis. He was operated at our hospital; all previously placed ostefixation material was removed, valgus osteotomy of 30 degrees was done as well as additional local osteoplasty using the commercial osteoindactive agent (Osteovit®. Postoperatively, we applied skin traction, bed rest and physical therapy. At the final follow­up, the patient was recovered completely. He is now painless, the legs are of equal length, range of movements in the left hip is full, life activity is normal. The X­ray shows that the femoral neck pseudoarthrosis is fully healed. Conclusion. This case is presented in order to encourage other colleagues to challenge the problematic situation such as this one. Also, we would like to remind them what one should think about and what should be taken into consideration in the primary treatment of femoral neck fractures in children. Valgus femoral osteotomy, as a part of the primary treatment of femoral neck fracture in children (identically as in the adults can prevent the occurrence of femoral neck pseudoarthrosis.

  1. Ipsilateral femoral shaft and vertical patella fracture: a case report

    Ozkan, Korhan; Eceviz, Engin; Sahin, Adem; Ugutmen, Ender

    2009-01-01

    Introduction A femoral shaft fracture with an ipsilateral patella fracture has been, to our knowledge, given only cursory attention in English-speaking literature. Case presentation A 15 year old male patient had hitten by a car to his motorcycle came to emergency room and he had been operated for his femoral shaft freacture and vertical patellar fracture which was iniatally missed. Conclusion To us it is vital to obtain CT scan of the patient’s knee if there is an ipsilateral femoral fracture with an ipsilateral knee effusion and a punction which reveals hematoma even in the absence of a fracture line seen in AP and lateral projections. PMID:19829933

  2. Aneurysm of the superficial femoral artery in an infant

    Watanabe, M.; Komuro, H.; Matoba, K.; Kaneko, M. [Dept. of Paediatric Surgery, Inst. of Clinical Medicine, Univ. of Tsukuba, Ibaraki (Japan); Niitsu, M.; Itai, Y. [Dept. of Radiology, Inst. of Clinical Medicine, Univ. of Tsukuba, Ibaraki (Japan)

    2003-04-01

    An isolated arterial aneurysm in childhood is extremely rare. We report a 1-year-old girl with an aneurysm of the right superficial femoral artery, presenting as an asymptomatic mass of the thigh. The aneurysm involved the whole superficial femoral artery (9 cm in length), and surgical treatment would have required replacement of the affected artery. Conservative treatment was chosen, influenced by the patient's rapid growth at that time. Non-invasive, 3-D contrast-enhanced magnetic resonance angiography (MRA) was useful as an alternative to conventional angiography for detailed evaluation of the femoral arteries, including the aneurysm. (orig.)

  3. Avascular osteonecrosis of the femoral condyle after arthroscopic surgery

    Al-Kaar, M.; Garcia, J.; Fritschy, D.; Bonvin, J.C.

    1997-01-01

    Avascular osteonecrosis of the femoral condyle after arthroscopic surgery. Retrospective review of 10 patients who presented with avascular necrosis of the ipsilateral femoral condyle following arthroscopic meniscectomy (9 medial, 1 lateral). The bone lesions were evaluated by radiography and MRI, which were repeated for few patients. MRI allows earlier diagnosis of avascular necrosis of the femoral condyle and offers an evaluation of extent of the lesions whose evolution is variable: 3 patients required a knee prosthesis, the other 7 patients were treated medically. (authors)

  4. Femoral artery pseudoaneurysm as a complication of angioplasty. How can it be prevented?

    Gupta, Prabha Nini; Salam Basheer, Abdul; Sukumaran, Gireesh Gomaty; Padmajan, Sabin; Praveen, Satheesan; Velappan, Praveen; Nair, Bigesh Unnikrishnan; Nair, Sandeep Govindan; Kunjuraman, Usha Kumari; Madthipat, Unnikrishnan; R, Jayadevan

    2013-01-01

    Femoral pseudoaneurysm is a common complication of repeated femoral puncture during cardiac catheterisation. We describe here the development of femoral pseudoaneurysms in a patient with Takayasu's arteritis, which healed in response to conservative treatment, and review the literature on the prevention and treatment of femoral pseudoaneurysm. PMID:27326111

  5. The Notch ligand delta-like 3 promotes tumor growth and inhibits Notch signaling in lung cancer cells in mice

    Deng, San-Ming; Yan, Xian-Chun; Liang, Liang; Wang, Li; Liu, Yuan; Duan, Juan-Li; Yang, Zi-Yan; Chang, Tian-Fang; Ruan, Bai; Zheng, Qi-Jun; Han, Hua

    2017-01-01

    Although it has been suggested that Dll3, one of the Notch ligands, promotes the proliferation and inhibits the apoptosis of cancer cells, the role of Dll3 in cancers remains unclear. In this study, we found that in the murine Lewis lung carcinoma (LLC) cells, the level of Dll3 mRNA changed upon tumor microenvironment (TME) stimulation, namely, decreased under hypoxia or stimulated with tumor necrosis factor (TNF)-α. Dll3 was also expressed at higher level in human lung carcinoma tissues than in the para-carcinoma tissues. Overexpression of Dll3 in LLC cells promoted cell proliferation and reduced apoptosis in vitro, and enhanced tumor growth when inoculated in vivo in mice. The Dll3-mediated proliferation could be due to increased Akt phosphorylation in LLC cells, because an Akt inhibitor counteracted Dll3-induced proliferation. Moreover, Dll3 overexpression promoted PI3K/Akt signaling through inhibiting Notch signaling. - Highlights: • The level of Dll3 in Lewis lung carcinoma changed upon tumor microenvironment (TME) stimulation, namely, decreased under hypoxia or stimulated with TNF-α. • The Dll3 was rarely detectable in the para-carcinoma tissues, but positive in 82.1% of NSCLC tissues from 84 patients. • Overexpression of Dll3 in LLC cells promoted tumor growth but did not remarkably alter TME after inoculated in mice. • Overexpression of Dll3 in LLC cells promoted cell proliferation and reduced apoptosis in vitro in an Akt-dependent way. • Dll3 overexpression promoted PI3K/Akt signaling through inhibiting Notch signaling.

  6. Bmi1 regulates murine intestinal stem cell proliferation and self-renewal downstream of Notch

    López-Arribillaga, Erika; Rodilla, Verónica; Pellegrinet, Luca

    2015-01-01

    Genetic data indicate that abrogation of Notch-Rbpj or Wnt-β-catenin pathways results in the loss of the intestinal stem cells (ISCs). However, whether the effect of Notch is direct or due to the aberrant differentiation of the transit-amplifying cells into post-mitotic goblet cells is unknown. T...

  7. Functional studies on the role of Notch signaling in Hydractinia development.

    Gahan, James M; Schnitzler, Christine E; DuBuc, Timothy Q; Doonan, Liam B; Kanska, Justyna; Gornik, Sebastian G; Barreira, Sofia; Thompson, Kerry; Schiffer, Philipp; Baxevanis, Andreas D; Frank, Uri

    2017-08-01

    The function of Notch signaling was previously studied in two cnidarians, Hydra and Nematostella, representing the lineages Hydrozoa and Anthozoa, respectively. Using pharmacological inhibition in Hydra and a combination of pharmacological and genetic approaches in Nematostella, it was shown in both animals that Notch is required for tentacle morphogenesis and for late stages of stinging cell maturation. Surprisingly, a role for Notch in neural development, which is well documented in bilaterians, was evident in embryonic Nematostella but not in adult Hydra. Adult neurogenesis in the latter seemed to be unaffected by DAPT, a drug that inhibits Notch signaling. To address this apparent discrepancy, we studied the role of Notch in Hydractinia echinata, an additional hydrozoan, in all life stages. Using CRISPR-Cas9 mediated mutagenesis, transgenesis, and pharmacological interference we show that Notch is dispensable for Hydractinia normal neurogenesis in all life stages but is required for the maturation of stinging cells and for tentacle morphogenesis. Our results are consistent with a conserved role for Notch in morphogenesis and nematogenesis across Cnidaria, and a lineage-specific loss of Notch dependence in neurogenesis in hydrozoans. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Notching of samples for fracture toughness' measurements via SEVNB Method of brittle ceramics

    Ribeiro, S.; Atilio, I.; Oliveira, M.R.; Garcia, G.C.R.; Rodrigues, J.A.

    2012-01-01

    The goal of this work is to present a notching machine to produce notches in ceramic bodies as well the choice and how to make the notches, using SiC produced by liquid phase sintering as experimental material. For the liquid sintering a mixture of Al 2 O 3 and Yb 2 O 3 as additive was applied. It was developed and built by an enterprise sited in Sao Carlos-SP an equipment, which permits to obtain polished notches in ceramic specimens to be fractured afterwards. That is to facilitate the measurement of K IC via the SEVNB method. Specimens of 10% of (Al 2 O 3 +Yb 2 O 3 ) containing SiC were sintered at 1950 deg C. Those specimens were machined and notched using razor blades and diamond pastes of 15, 9, 6, 3, 1 and 0.25 μm of particle size. The built machine to notch specimens is installed at DEMAR-EEL-USP, and it is said to be the first of that type in Brazil. The results showed that depending on the thickness of the razor blade and the size of the diamond particles, it can be curried out notches with distinct tip radius and notch depth values. (author)

  9. Notch root strain measurement of WE43-T6 magnesium alloy using electronic speckle pattern interferometry

    Liew, H.L.; Ahmad, A.; Ramesh, S.; Purbolaksono, J.

    2013-01-01

    Highlights: • The use of ESPI for measuring total strains at the notch root of specimens. • Fine meshing in micron scale at the notch root regions. • The maximum elastic strain is shifted to be further away from the notch root tip. - Abstract: The notch root elasto-plastic strains of circumferentially grooved round specimen of cast magnesium WE43-T6 were experimentally measured using the electronic speckle pattern interferometry (ESPI) and numerically evaluated using the finite element analysis (FEA). The specimens have notch radii of 1.6 mm and 0.8 mm and an opening angle of 60°. The technique of ESPI showed its accuracy in measuring three-dimensional surface deformations on large negatively curved manifolds. The measured nominal stress for rupture is well beyond the ultimate strength, suggesting the existence of significant biaxial stress at the notch root region. The ESPI-based strains on the notch tips were shown to be in agreement with those evaluated by the FEA. The FEA also showed that the maximum elastic strain is shifted away from the notch root surface as the plastic strain is predominant

  10. Stress concentration factors for an internally pressurized circular vessel containing a radial U-notch

    Carvalho, E.A. de

    2005-01-01

    This paper evaluates the stress concentration factors for an internally pressurized cylinder containing a radial U-notch along its length. This work studies the cases where the external to internal radius ratio (Ψ) is equal to 1.26, 1.52, 2.00, and 3.00 and the notch radius to internal radius ratio (Φ) is fixed and equal to 0.026. The U-notch depth varies from 0.1 to 0.6 of the wall thickness. Results are also presented for a fixed size semi-circular notch. Hoop stresses at the external wall are presented, showing regions where the stress matches the nominal one and the favourable places to install strain sensors. The finite element method is used to determine the stress concentration factors (K t ) for the above described situations and for a special case where a varying semi-circular notch is present with Ψ=3.00. This notch depth varies from 0.013 to 0.3 of the wall thickness. It is pointed out that even relatively small notches introduce large stress concentrations and disrupt the hoop stress distribution all over the cross section. Results are also compared to an example found in the literature for semi-circular notches and K t curves for both cases present the same shape

  11. Therapeutic NOTCH3 cysteine correction in CADASIL using exon skipping: in vitro proof of concept

    Rutten, J.W.; Dauwerse, H.G.; Peters, D.J.; Goldfarb, A.; Venselaar, H.; Haffner, C.; Ommen, G.J. van; Aartsma-Rus, A.M.; Oberstein, S.A.

    2016-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, or CADASIL, is a hereditary cerebral small vessel disease caused by characteristic cysteine altering missense mutations in theNOTCH3gene.NOTCH3mutations in CADASIL result in an uneven number of cysteine

  12. Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch

    Amsen, Derk; Antov, Andrey; Jankovic, Dragana; Sher, Alan; Radtke, Freddy; Souabni, Abdallah; Busslinger, Meinrad; McCright, Brent; Gridley, Thomas; Flavell, Richard A.

    2007-01-01

    CD4(+) T helper cells differentiate into T helper 1 (Th1) or Th2 effector lineages, which orchestrate immunity to different types of microbes. Both Th1 and Th2 differentiation can be induced by Notch, but what dictates which of these programs is activated in response to Notch is not known. By using

  13. Perivascular delivery of Notch 1 siRNA inhibits injury-induced arterial remodeling.

    Eileen M Redmond

    Full Text Available To determine the efficacy of perivascular delivery of Notch 1 siRNA in preventing injury-induced arterial remodeling.Carotid artery ligation was performed to induce arterial remodeling. After 14 days, morphometric analysis confirmed increased vSMC growth and subsequent media thickening and neointimal formation. Laser capture microdissection, quantitative qRT-PCR and immunoblot analysis of medial tissue revealed a significant increase in Notch1 receptor and notch target gene, Hrt 1 and 2 expression in the injured vessels. Perivascular delivery of Notch 1 siRNA by pluronic gel inhibited the injury-induced increase in Notch 1 receptor and target gene expression when compared to scrambled siRNA controls while concomitantly reducing media thickening and neointimal formation to pre-injury, sham-operated levels. Selective Notch 1 knockdown also reversed the injury-induced inhibition of pro-apoptotic Bax expression while decreasing injury-induced anti-apoptotic Bcl-XL expression to sham-operated control levels. In parallel experiments, proliferative cyclin levels, as measured by PCNA expression, were reversed to sham-operated control levels following selective Notch 1 knockdown.These results suggest that injury-induced arterial remodeling can be successfully inhibited by localized perivascular delivery of Notch 1 siRNA.

  14. Fringe proteins modulate Notch-ligand cis and trans interactions to specify signaling states.

    LeBon, Lauren; Lee, Tom V; Sprinzak, David; Jafar-Nejad, Hamed; Elowitz, Michael B

    2014-09-25

    The Notch signaling pathway consists of multiple types of receptors and ligands, whose interactions can be tuned by Fringe glycosyltransferases. A major challenge is to determine how these components control the specificity and directionality of Notch signaling in developmental contexts. Here, we analyzed same-cell (cis) Notch-ligand interactions for Notch1, Dll1, and Jag1, and their dependence on Fringe protein expression in mammalian cells. We found that Dll1 and Jag1 can cis-inhibit Notch1, and Fringe proteins modulate these interactions in a way that parallels their effects on trans interactions. Fringe similarly modulated Notch-ligand cis interactions during Drosophila development. Based on these and previously identified interactions, we show how the design of the Notch signaling pathway leads to a restricted repertoire of signaling states that promote heterotypic signaling between distinct cell types, providing insight into the design principles of the Notch signaling system, and the specific developmental process of Drosophila dorsal-ventral boundary formation.

  15. RBP-Jκ-dependent Notch signaling enhances retinal pigment epithelial cell proliferation in transgenic mice.

    Schouwey, K; Aydin, I T; Radtke, F; Beermann, F

    2011-01-20

    The Notch signaling pathway is an ubiquitous cell-cell interaction mechanism, which is essential in controlling processes like cell proliferation, cell fate decision, differentiation or stem cell maintenance. Recent data have shown that Notch signaling is RBP-Jκ-dependent in melanocytes, being required for survival of these pigment cells that are responsible for coloration of the skin and hairs in mammals. In addition, Notch is believed to function as an oncogene in melanoma, whereas it is a tumor suppressor in mouse epidermis. In this study, we addressed the implication of the Notch signaling in the development of another population of pigment cells forming the retinal pigment epithelium (RPE) in mammalian eyes. The constitutive activity of Notch in Tyrp1::NotchIC/° transgenic mice enhanced RPE cell proliferation, and the resulting RPE-derived pigmented tumor severely affected the overall eye structure. This RPE cell proliferation is dependent on the presence of the transcription factor RBP-Jκ, as it is rescued in mice lacking RBP-Jκ in the RPE. In conclusion, Notch signaling in the RPE uses the canonical pathway, which is dependent on the transcription factor RBP-Jκ. In addition, it is of importance for RPE development, and constitutive Notch activity leads to hyperproliferation and benign tumors of these pigment cells.

  16. Cell proliferation control by Notch signalling during imaginal discs development in Drosophila

    Carlos Estella

    2015-02-01

    Full Text Available The Notch signalling pathway is evolutionary conserved and participates in numerous developmental processes, including the control of cell proliferation. However, Notch signalling can promote or restrain cell division depending on the developmental context, as has been observed in human cancer where Notch can function as a tumor suppressor or an oncogene. Thus, the outcome of Notch signalling can be influenced by the cross-talk between Notch and other signalling pathways. The use of model organisms such as Drosophila has been proven to be very valuable to understand the developmental role of the Notch pathway in different tissues and its relationship with other signalling pathways during cell proliferation control. Here we review recent studies in Drosophila that shed light in the developmental control of cell proliferation by the Notch pathway in different contexts such as the eye, wing and leg imaginal discs. We also discuss the autonomous and non-autonomous effects of the Notch pathway on cell proliferation and its interactions with different signalling pathways.

  17. Minocycline attenuates the development of diabetic neuropathy by inhibiting spinal cord Notch signaling in rat.

    Yang, Cheng; Gao, Jie; Wu, Banglin; Yan, Nuo; Li, Hui; Ren, Yiqing; Kan, Yufei; Liang, Jiamin; Jiao, Yang; Yu, Yonghao

    2017-10-01

    We studied the effects of minocycline (an inhibitor of microglial activation) on the expression and activity of Notch-1 receptor, and explored the therapeutic efficacy of minocycline combined with Notch inhibitor DAPT in the treatment of diabetic neuropathic pain (DNP). Diabetic rat model was established by intraperitoneal injection (ip) of Streptozotocin (STZ). Expression and activity of Notch-1 and expression of macrophage/microglia marker Iba-1 were detected by WB. Diabetes induction significantly attenuated sciatic nerve conduction velocity, and dramatically augmented the expression and the activity of Notch-1 in the lumbar enlargement of the spinal cord. Minocycline treatment, however, accelerated the decreased conduction velocity of sciatic nerve and suppressed Notch-1expression and activity in diabetic rats. Similar to DAPT treatment, minocycline administration also prolonged thermal withdrawal latency (TWL) and increase mechanical withdrawal threshold (MWT) in diabetic rats in response to heat or mechanical stimulation via inhibition the expression and the activity of Notch-1 in spinal cord. Combination of DAPT and minocycline further inhibited Notch-1 receptor signaling and reduce neuropathic pain exhibited as improved TWL and MWT. Our study revealed a novel mechanism of Notch-1 receptor inhibition in spinal cord induced by minocycline administration, and suggested that the combination of minocycline and DAPT has the potential to treat DNP. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Redundant Notch1 and Notch2 signaling is necessary for IFNγ secretion by T helper 1 cells during infection with Leishmania major.

    Floriane Auderset

    Full Text Available The protective immune response to intracellular parasites involves in most cases the differentiation of IFNγ-secreting CD4(+ T helper (Th 1 cells. Notch receptors regulate cell differentiation during development but their implication in the polarization of peripheral CD4(+ T helper 1 cells is not well understood. Of the four Notch receptors, only Notch1 (N1 and Notch2 (N2 are expressed on activated CD4(+ T cells. To investigate the role of Notch in Th1 cell differentiation following parasite infection, mice with T cell-specific gene ablation of N1, N2 or both (N1N2(ΔCD4Cre were infected with the protozoan parasite Leishmania major. N1N2(ΔCD4Cre mice, on the C57BL/6 L. major-resistant genetic background, developed unhealing lesions and uncontrolled parasitemia. Susceptibility correlated with impaired secretion of IFNγ by draining lymph node CD4(+ T cells and increased secretion of the IL-5 and IL-13 Th2 cytokines. Mice with single inactivation of N1 or N2 in their T cells were resistant to infection and developed a protective Th1 immune response, showing that CD4(+ T cell expression of N1 or N2 is redundant in driving Th1 differentiation. Furthermore, we show that Notch signaling is required for the secretion of IFNγ by Th1 cells. This effect is independent of CSL/RBP-Jκ, the major effector of Notch receptors, since L. major-infected mice with a RBP-Jκ deletion in their T cells were able to develop IFNγ-secreting Th1 cells, kill parasites and heal their lesions. Collectively, we demonstrate here a crucial role for RBP-Jκ-independent Notch signaling in the differentiation of a functional Th1 immune response following L. major infection.

  19. Notch signaling activation in human embryonic stem cells is required for embryonic but not trophoblastic lineage commitment

    Yu, Xiaobing; Zou, Jizhong; Ye, Zhaohui; Hammond, Holly; Chen, Guibin; Tokunaga, Akinori; Mali, Prashant; Li, Yue-Ming; Civin, Curt; Gaiano, Nicholas; Cheng, Linzhao

    2008-01-01

    The Notch signaling pathway plays important roles in cell fate determination during embryonic development and adult life. In this study, we focus on the role of Notch signaling in governing cell fate choices in human embryonic stem (hES) cells. Using genetic and pharmacological approaches, we achieved both blockade and conditional activation of Notch signaling in several hES cell lines. We report here that activation of Notch signaling is required for undifferentiated hES cells to form the pr...

  20. Mutual inactivation of Notch receptors and ligands facilitates developmental patterning.

    David Sprinzak

    2011-06-01

    Full Text Available Developmental patterning requires juxtacrine signaling in order to tightly coordinate the fates of neighboring cells. Recent work has shown that Notch and Delta, the canonical metazoan juxtacrine signaling receptor and ligand, mutually inactivate each other in the same cell. This cis-interaction generates mutually exclusive sending and receiving states in individual cells. It generally remains unclear, however, how this mutual inactivation and the resulting switching behavior can impact developmental patterning circuits. Here we address this question using mathematical modeling in the context of two canonical pattern formation processes: boundary formation and lateral inhibition. For boundary formation, in a model motivated by Drosophila wing vein patterning, we find that mutual inactivation allows sharp boundary formation across a broader range of parameters than models lacking mutual inactivation. This model with mutual inactivation also exhibits robustness to correlated gene expression perturbations. For lateral inhibition, we find that mutual inactivation speeds up patterning dynamics, relieves the need for cooperative regulatory interactions, and expands the range of parameter values that permit pattern formation, compared to canonical models. Furthermore, mutual inactivation enables a simple lateral inhibition circuit architecture which requires only a single downstream regulatory step. Both model systems show how mutual inactivation can facilitate robust fine-grained patterning processes that would be difficult to implement without it, by encoding a difference-promoting feedback within the signaling system itself. Together, these results provide a framework for analysis of more complex Notch-dependent developmental systems.

  1. Neuropsychological findings in a patient with Kernohan's notch.

    Clement, V L; Sherer, M

    1996-05-01

    This case report describes the use of neuropsychological testing to Iocalize and diagnose lesions The testing was instrumental in disentangling contradictory symptoms to reveal a Kernohan's notch (later confirmed by MRI), thus ruling out incorrect diagnoses We describe the case of a 36-year-old right-handed man who developed a left epidural hematoma after suffering head trauma from a blunt instrument Sequelae 2 months post-injury included left hemiparesis (ipsilateral to the lesion), dysphonic speech, severe naming/word-finding deficits, and severe memory impairment This patient's symptom pattern presented somewhat of a mystery as his cognitive deficits appeared consistent with left hemisphere damage, while his left motor symptoms suggested right hemisphere damage Medical records were inconsistent Deficits on neuropsychological testing at 3 months post-injury included impairment in verbal and visual memory, confrontation naming, and left-sided motor function Attention, visual-spatial skills, nonverbal problem solving, and right motor speed and coordination were intact A herniation syndrome, Kernohan's notch, was considered to be the most likely explanation This phenomenon occurs when a mass occupying lesion causes significant midline shift of the midbrain, pressing the contralateral cerebral peduncle against the tentorium This pressure produces an ischemic infact in the region of the corticospinal (motor) pathways Subsequent MRI confirmed a lesion in the right cerebral crus The pattern of neuropsychological finding in this patient is discussed.

  2. Design of Two Novel Dual Band-Notched UWB Antennas

    Bing Li

    2012-01-01

    Full Text Available Two novel dual band-notched ultra-wideband (UWB printed monopole antennas with simple structure and small size are presented. The size of both antennas is 25×25×0.8 mm3. The bandwidth of one of the proposed antenna can be from 2.7 GHz to 36.8 GHz, except the bandwidth of 3.2–3.9 GHz for WiMAX applications and 5.14–5.94 GHz for WLAN applications. The bandwidth of the other is ranging for 2.7 to 41.1 GHz, except the bandwidth of 3.2–3.9 GHz for WiMAX applications and 4.8–5.9 GHz for WLAN applications. Bandwidths of the antennas are about 512% and 455% wider than those of conventional band-notched UWB antennas, respectively. In addition, the time-domain characteristics of the two antennas are investigated to show the difference between both antennas.

  3. Tumor Architecture and Notch Signaling Modulate Drug Response in Basal Cell Carcinoma.

    Eberl, Markus; Mangelberger, Doris; Swanson, Jacob B; Verhaegen, Monique E; Harms, Paul W; Frohm, Marcus L; Dlugosz, Andrzej A; Wong, Sunny Y

    2018-02-12

    Hedgehog (Hh) pathway inhibitors such as vismodegib are highly effective for treating basal cell carcinoma (BCC); however, residual tumor cells frequently persist and regenerate the primary tumor upon drug discontinuation. Here, we show that BCCs are organized into two molecularly and functionally distinct compartments. Whereas interior Hh + /Notch + suprabasal cells undergo apoptosis in response to vismodegib, peripheral Hh +++ /Notch - basal cells survive throughout treatment. Inhibiting Notch specifically promotes tumor persistence without causing drug resistance, while activating Notch is sufficient to regress already established lesions. Altogether, these findings suggest that the three-dimensional architecture of BCCs establishes a natural hierarchy of drug response in the tumor and that this hierarchy can be overcome, for better or worse, by modulating Notch. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Lunatic fringe-mediated Notch signaling regulates adult hippocampal neural stem cell maintenance.

    Semerci, Fatih; Choi, William Tin-Shing; Bajic, Aleksandar; Thakkar, Aarohi; Encinas, Juan Manuel; Depreux, Frederic; Segil, Neil; Groves, Andrew K; Maletic-Savatic, Mirjana

    2017-07-12

    Hippocampal neural stem cells (NSCs) integrate inputs from multiple sources to balance quiescence and activation. Notch signaling plays a key role during this process. Here, we report that Lunatic fringe ( Lfng), a key modifier of the Notch receptor, is selectively expressed in NSCs. Further, Lfng in NSCs and Notch ligands Delta1 and Jagged1, expressed by their progeny, together influence NSC recruitment, cell cycle duration, and terminal fate. We propose a new model in which Lfng-mediated Notch signaling enables direct communication between a NSC and its descendants, so that progeny can send feedback signals to the 'mother' cell to modify its cell cycle status. Lfng-mediated Notch signaling appears to be a key factor governing NSC quiescence, division, and fate.

  5. Avascular osteonecrosis of the femoral condyle after arthroscopic surgery; Osteonecrose aseptique du condyle femoral apres meniscectomie par voie arthroscopique

    Al-Kaar, M.; Garcia, J. [Hopital Cantonal Geneve, Geneva (Switzerland); Fritschy, D.; Bonvin, J.C. [Policlinique de Chirurgie, Hopital Cantonal Universitaire, Geneve (Switzerland)

    1997-04-01

    Avascular osteonecrosis of the femoral condyle after arthroscopic surgery. Retrospective review of 10 patients who presented with avascular necrosis of the ipsilateral femoral condyle following arthroscopic meniscectomy (9 medial, 1 lateral). The bone lesions were evaluated by radiography and MRI, which were repeated for few patients. MRI allows earlier diagnosis of avascular necrosis of the femoral condyle and offers an evaluation of extent of the lesions whose evolution is variable: 3 patients required a knee prosthesis, the other 7 patients were treated medically. (authors). 21 refs.

  6. AKAP200 promotes Notch stability by protecting it from Cbl/lysosome-mediated degradation in Drosophila melanogaster.

    Neeta Bala Tannan

    2018-01-01

    Full Text Available AKAP200 is a Drosophila melanogaster member of the "A Kinase Associated Protein" family of scaffolding proteins, known for their role in the spatial and temporal regulation of Protein Kinase A (PKA in multiple signaling contexts. Here, we demonstrate an unexpected function of AKAP200 in promoting Notch protein stability. In Drosophila, AKAP200 loss-of-function (LOF mutants show phenotypes that resemble Notch LOF defects, including eye patterning and sensory organ specification defects. Through genetic interactions, we demonstrate that AKAP200 interacts positively with Notch in both the eye and the thorax. We further show that AKAP200 is part of a physical complex with Notch. Biochemical studies reveal that AKAP200 stabilizes endogenous Notch protein, and that it limits ubiquitination of Notch. Specifically, our genetic and biochemical evidence indicates that AKAP200 protects Notch from the E3-ubiquitin ligase Cbl, which targets Notch to the lysosomal pathway. Indeed, we demonstrate that the effect of AKAP200 on Notch levels depends on the lysosome. Interestingly, this function of AKAP200 is fully independent of its role in PKA signaling and independent of its ability to bind PKA. Taken together, our data indicate that AKAP200 is a novel tissue specific posttranslational regulator of Notch, maintaining high Notch protein levels and thus promoting Notch signaling.

  7. Notch signaling regulates platelet-derived growth factor receptor-β expression in vascular smooth muscle cells

    Jin, S.; Hansson, E.M.; Tikka, S.; Lanner, F.; Sahlgren, C.; Farnebo, F.; Baumann, M.; Kalimo, H.; Lendahl, U.

    2008-01-01

    Notch signaling is critically important for proper architecture of the vascular system, and mutations in NOTCH3 are associated with CADASIL, a stroke and dementia syndrome with vascular smooth muscle cell (VSMC) dysfunction. In this report, we link Notch signaling to platelet-derived growth factor

  8. AKAP200 promotes Notch stability by protecting it from Cbl/lysosome-mediated degradation in Drosophila melanogaster.

    Bala Tannan, Neeta; Collu, Giovanna; Humphries, Ashley C; Serysheva, Ekatherina; Weber, Ursula; Mlodzik, Marek

    2018-01-01

    AKAP200 is a Drosophila melanogaster member of the "A Kinase Associated Protein" family of scaffolding proteins, known for their role in the spatial and temporal regulation of Protein Kinase A (PKA) in multiple signaling contexts. Here, we demonstrate an unexpected function of AKAP200 in promoting Notch protein stability. In Drosophila, AKAP200 loss-of-function (LOF) mutants show phenotypes that resemble Notch LOF defects, including eye patterning and sensory organ specification defects. Through genetic interactions, we demonstrate that AKAP200 interacts positively with Notch in both the eye and the thorax. We further show that AKAP200 is part of a physical complex with Notch. Biochemical studies reveal that AKAP200 stabilizes endogenous Notch protein, and that it limits ubiquitination of Notch. Specifically, our genetic and biochemical evidence indicates that AKAP200 protects Notch from the E3-ubiquitin ligase Cbl, which targets Notch to the lysosomal pathway. Indeed, we demonstrate that the effect of AKAP200 on Notch levels depends on the lysosome. Interestingly, this function of AKAP200 is fully independent of its role in PKA signaling and independent of its ability to bind PKA. Taken together, our data indicate that AKAP200 is a novel tissue specific posttranslational regulator of Notch, maintaining high Notch protein levels and thus promoting Notch signaling.

  9. An Evolutionary-Conserved Function of Mammalian Notch Family Members as Cell Adhesion Molecules

    Murata, Akihiko; Yoshino, Miya; Hikosaka, Mari; Okuyama, Kazuki; Zhou, Lan; Sakano, Seiji; Yagita, Hideo; Hayashi, Shin-Ichi

    2014-01-01

    Notch family members were first identified as cell adhesion molecules by cell aggregation assays in Drosophila studies. However, they are generally recognized as signaling molecules, and it was unclear if their adhesion function was restricted to Drosophila. We previously demonstrated that a mouse Notch ligand, Delta-like 1 (Dll1) functioned as a cell adhesion molecule. We here investigated whether this adhesion function was conserved in the diversified mammalian Notch ligands consisted of two families, Delta-like (Dll1, Dll3 and Dll4) and Jagged (Jag1 and Jag2). The forced expression of mouse Dll1, Dll4, Jag1, and Jag2, but not Dll3, on stromal cells induced the rapid and enhanced adhesion of cultured mast cells (MCs). This was attributed to the binding of Notch1 and Notch2 on MCs to each Notch ligand on the stromal cells themselves, and not the activation of Notch signaling. Notch receptor-ligand binding strongly supported the tethering of MCs to stromal cells, the first step of cell adhesion. However, the Jag2-mediated adhesion of MCs was weaker and unlike other ligands appeared to require additional factor(s) in addition to the receptor-ligand binding. Taken together, these results demonstrated that the function of cell adhesion was conserved in mammalian as well as Drosophila Notch family members. Since Notch receptor-ligand interaction plays important roles in a broad spectrum of biological processes ranging from embryogenesis to disorders, our finding will provide a new perspective on these issues from the aspect of cell adhesion. PMID:25255288

  10. early functional outcome of distal femoral fractures at kenyatta

    The leading cause was RTA, followed by falls from a height. ... Distal femoral fractures cause considerable morbidity .... as means and standard deviations. .... Anaesthesia. Spinal. 37 (80). General Anaesthesia (GA). 9 (20). Transfusion.

  11. Femoral neck fractures complicating gaucher disease in children

    Goldman, A.B.; Jacobs, B.

    1984-09-01

    In normal children, fractures of the femoral neck are uncommon and accompany severe trauma and multiple injuries elsewhere in the skeleton. In children with Gaucher disease, a rare hereditary disorder of lipid metabolism, midcervical or basicervical fractures can occur with minor or no trauma and without other injury to the skeleton. Three children with Gaucher disease who developed pathologic fractures of the femoral neck are described. In all three, the fractures occurred between five and nine years of age, and the fracture lines passed through areas of abnormal bone characterized by poorly defined patches of increased and decreased density and cortical thinning along the medial femoral necks. In the affected hips, there was no evidence of avascular necrosis of the femoral heads at the time of injury. One child's fracture was preceeded by multiple bone 'crisis' localized to the proximal femora.

  12. Femoral neck fractures complicating gaucher disease in children

    Goldman, A.B.; Jacobs, B.

    1984-01-01

    In normal children, fractures of the femoral neck are uncommon and accompany severe trauma and multiple injuries elsewhere in the skeleton. In children with Gaucher disease, a rare hereditary disorder of lipid metabolism, midcervical or basicervical fractures can occur with minor or no trauma and without other injury to the skeleton. Three children with Gaucher disease who developed pathologic fractures of the femoral neck are described. In all three, the fractures occurred between five and nine years of age, and the fracture lines passed through areas of abnormal bone characterized by poorly defined patches of increased and decreased density and cortical thinning along the medial femoral necks. In the affected hips, there was no evidence of avascular necrosis of the femoral heads at the time of injury. One child's fracture was preceeded by multiple bone 'crisis' localized to the proximal femora. (orig.)

  13. Effectiveness of plate augmentation for femoral shaft nonunion after nailing

    Chin-Jung Lin

    2012-08-01

    Conclusion: Plate augmentation with retention of the nail with autologous bone grafting may be an effective and reliable alternative in treating nonunion of the femoral shaft fracture after open reduction and internal fixation with intramedullary nail.

  14. 'Femoral head necrosis' in metabolic and hormonal osteopathies

    Heuck, F.H.W.; Treugut, H.

    1984-01-01

    The pathogenesis of bone necrosis is discussed with special attention and with respect to metabolic, hormonal, and vascular factors. The influence of statics and dynamics of the hip joint bones for the development of aseptic necrosis are discussed. 45 patients with ''idiopathic femoral head necroses'' were observed, including 6 cases of renal osteopathy following renal transplantation and immune suppression therapy, 14 cases of long term corticoid therapy, and 11 cases of liver diseases of different genesis. The femoral head necrosis understood as complication of an osteopathy. In our patients there were 31 males and 14 females - which means higher involvement of males. Plain radiological findings and CT-findings of changes of the femoral heat structure in different stages of the disease are described. Early diagnosis of metabolic and hormonal osteopathies is demanded for a joint keeping therapy of the beginning femoral head necrosis. (orig.) [de

  15. Short-term outcome of patients with closed comminuted femoral ...

    Short-term outcome of patients with closed comminuted femoral shaft fracture treated with locking intramedullary sign nail at Muhimbili Orthopaedic Institute in Tanzania. Billy T. Haonga, Felix S. Mrita, Edmundo E. Ndalama, Jackline E. Makupa ...

  16. Delayed appearance of hypaesthesia and paralysis after femoral nerve block

    Stefan Landgraeber

    2012-03-01

    Full Text Available We report on a female patient who underwent an arthroscopy of the right knee and was given a continuous femoral nerve block catheter. The postoperative course was initially unremarkable, but when postoperative mobilisation was commenced, 18 hours after removal of the catheter, the patient noticed paralysis and hypaesthesia. Examination confirmed the diagnosis of femoral nerve dysfunction. Colour duplex sonography of the femoral artery and computed tomography of the lumbar spine and pelvis yielded no pathological findings. Overnight the neurological deficits decreased without therapy and were finally no longer detectable. We speculate that during the administration of the local anaesthetic a depot formed, localised in the medial femoral intermuscular septa, which was leaked after first mobilisation. To our knowledge no similar case has been published up to now. We conclude that patients who are treated with a nerve block should be informed and physician should be aware that delayed neurological deficits are possible.

  17. Incidence and predictors of post-catheterization femoral artery pseudoaneurysms

    Hussein Heshmat Kassem

    2013-09-01

    Conclusion: Femoral artery pseudoaneurysms are not uncommon. Female gender, obesity, hypertension, the use of antiplatelet and/or anticoagulant therapy and faulty puncture techniques are independent risk factors for FAPs.

  18. Delayed appearance of hypaesthesia and paralysis after femoral nerve block

    Landgraeber, Stefan; Albrecht, Thomas; Reischuck, Ulrich; von Knoch, Marius

    2012-01-01

    We report on a female patient who underwent an arthroscopy of the right knee and was given a continuous femoral nerve block catheter. The postoperative course was initially unremarkable, but when postoperative mobilisation was commenced, 18 hours after removal of the catheter, the patient noticed paralysis and hypaesthesia. Examination confirmed the diagnosis of femoral nerve dysfunction. Colour duplex sonography of the femoral artery and computed tomography of the lumbar spine and pelvis yielded no pathological findings. Overnight the neurological deficits decreased without therapy and were finally no longer detectable. We speculate that during the administration of the local anaesthetic a depot formed, localised in the medial femoral intermuscular septa, which was leaked after first mobilisation. To our knowledge no similar case has been published up to now. We conclude that patients who are treated with a nerve block should be informed and physician should be aware that delayed neurological deficits are possible. PMID:22577509

  19. Femoral neck fractures complicating gaucher disease in children

    Goldman, A B; Jacobs, B

    1984-09-01

    In normal children, fractures of the femoral neck are uncommon and accompany severe trauma and multiple injuries elsewhere in the skeleton. In children with Gaucher disease, a rare hereditary disorder of lipid metabolism, midcervical or basicervical fractures can occur with minor or no trauma and without other injury to the skeleton. Three children with Gaucher disease who developed pathologic fractures of the femoral neck are described. In all three, the fractures occurred between five and nine years of age, and the fracture lines passed through areas of abnormal bone characterized by poorly defined patches of increased and decreased density and cortical thinning along the medial femoral necks. In the affected hips, there was no evidence of avascular necrosis of the femoral heads at the time of injury. One child's fracture was preceeded by multiple bone 'crisis' localized to the proximal femora.

  20. Validation of a new classification system for interprosthetic femoral fractures.

    Pires, Robinson Esteves Santos; Silveira, Marcelo Peixoto Sena; Resende, Alessandra Regina da Silva; Junior, Egidio Oliveira Santana; Campos, Tulio Vinicius Oliveira; Santos, Leandro Emilio Nascimento; Balbachevsky, Daniel; Andrade, Marco Antônio Percope de

    2017-07-01

    Interprosthetic femoral fracture (IFF) incidence is gradually increasing as the population is progressively ageing. However, treatment remains challenging due to several contributing factors, such as poor bone quality, patient comorbidities, small interprosthetic fragment, and prostheses instability. An effective and specific classification system is essential to optimize treatment management, therefore diminishing complication rates. This study aims to validate a previously described classification system for interprosthetic femoral fractures. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Incidence and predictors of post-catheterization femoral artery pseudoaneurysms

    Kassem, Hussein Heshmat; Elmahdy, Mahmoud Farouk; Ewis, Essam Baligh; Mahdy, Soilman Ghareeb

    2013-01-01

    Background: Femoral artery pseudoaneurysm (FAP) is a troublesome complication after transfemoral catheter procedures. The incidence and predictors of FAP as a separate entity have not been extensively studied. Aim: Detect prospectively the incidence and predictors of post catheterization FAP. Methods: From June 2009 till June 2011, we prospectively included all patients who underwent catheterization from the femoral approach. Duplex ultrasound was performed in cases with clinical suspic...

  2. Mechanical Characterization of Femoral Cartilage Under Unicompartimental Osteoarthritis

    Vidal-Lesso, A.; Ledesma-Orozco, E.; Daza-Benítez, L.; Lesso-Arroyo, R.

    2014-01-01

    The aim of this study was to determine the mechanical properties and thickness of articular cartilage in the unaffected femoral regions in cases of unicompartimental osteoarthritis on the knees. The specimens were tested using a 3mm plane-ended cylindrical indenter and a displacement of 0.5mm was applied at specific points in seven femoral knee cartilages with unicompartimental osteoarthritis. The thickness, stiffness, elastic modulus, shear modulus and bulk modulus were obtained. These prope...

  3. OUTCOME OF INTERTROCHANTERIC FRACTURES TREATED WITH SHORT FEMORAL NAIL

    Yadkikar Shriniwas V, Yadkikar Vishnu S, Patel Mayank, Dhruvilkumar Gandhi, Kunkulol Rahul

    2015-07-01

    Full Text Available Aim: To study the functional and anatomical outcome of Inter trochanteric fractures of femur treated with Short femoral nail. Method: This was retrospective study carried out in which 60 patients (50 Male & 10 Female of 5th to 8th decade of life who underwent Short femoral nail fixation for both Stable & unstable Inter Trochanteric fractures. From the records each patient data was assessed for time required for mobilization, average fracture healing time, degree and grade of hip range of movements, complications, anatomical reduction achieved using Short femoral nail fixation. Results: 55 cases achieved Anatomical reduction. Good to Excellent Hip range of Motion was in 55 (90 % cases. Fracture union was seen in all cases. No evidence of Z Effect, AVN of femoral head, Implant failure, Fracture of femoral shaft below the Nail tip was seen in any case, However Reverse Z Effect was seen in 4 & shortening of less than 2 cm was seen in 2 cases, External rotation of 10 degree was seen in1 case. Average fracture Union time was 14 weeks. Conclusion: Short femoral nail appears to be better implant for fixation of both Stable & unstable Inter Trochanteric fractures as it fulfills the biomechanical demands being minimally invasive, less blood loss , it prevents excessive varus collapse at fracture site, produces less stress riser effect below the nail tip, Short operative time, Facilitates early mobilization & functional recovery of patients. But Anatomical fracture reduction & optimal implant placement are absolutely must for better results.

  4. Femoral Neck Shaft Angle in Men with Fragility Fractures

    S. P. Tuck

    2011-01-01

    Full Text Available Introduction. Femoral neck shaft angle (NSA has been reported to be an independent predictor of hip fracture risk in men. We aimed to assess the role of NSA in UK men. Methods. The NSA was measured manually from the DXA scan printout in men with hip (62, 31 femoral neck and 31 trochanteric, symptomatic vertebral (91, and distal forearm (67 fractures and 389 age-matched control subjects. Age, height, weight, and BMD (g/cm2: lumbar spine, femoral neck, and total femur measurements were performed. Results. There was no significant difference in mean NSA between men with femoral neck and trochanteric hip fractures, so all further analyses of hip fractures utilised the combined data. There was no difference in NSA between those with hip fractures and those without (either using the combined data or analysing trochanteric and femoral neck shaft fractures separately, nor between fracture subjects as a whole and controls. Mean NSA was smaller in those with vertebral fractures (129.2° versus 131°: P=0.001, but larger in those with distal forearm fractures (129.8° versus 128.5°: P=0.01. Conclusions. The conflicting results suggest that femoral NSA is not an important determinant of hip fracture risk in UK men.

  5. Necrosis de la cabeza femoral tras fractura del cuello femoral tratada mediante osteosíntesis

    Martínez Martín, Angel Antonio; Panisello Sebastiá, Juan José; Lallana Duplá, J.; Herrera Rodríguez, Antonio

    2000-01-01

    Se presenta un análisis retrospectivo de las necrosis aparecidas en 233 pacientes con fractura de cuello femoral fijada con tornillos de esponjosa. La edad media fue de 80,6 años. Setenta y un pacientes (26%) tuvieron una fractura no desplazada (Garden I o II) y 172 (74%) una fractura desplazada (Garden III o IV). Seis meses tras la cirugía 170 pacientes sobrevivían (72,9%). Treinta y cuatro de ellos (20%) habían desarrollado necrosis y 10 (5,9%) colapso. Tras un seguimiento de 12 meses 114 p...

  6. Inhibition of Notch1 promotes hedgehog signalling in a HES1-dependent manner in chondrocytes and exacerbates experimental osteoarthritis.

    Lin, Neng-Yu; Distler, Alfiya; Beyer, Christian; Philipi-Schöbinger, Ariella; Breda, Silvia; Dees, Clara; Stock, Michael; Tomcik, Michal; Niemeier, Andreas; Dell'Accio, Francesco; Gelse, Kolja; Mattson, Mark P; Schett, Georg; Distler, Jörg Hw

    2016-11-01

    Notch ligands and receptors have recently been shown to be differentially expressed in osteoarthritis (OA). We aim to further elucidate the functional role of Notch signalling in OA using Notch1 antisense transgenic (Notch1 AS) mice. Notch and hedgehog signalling were analysed by real-time PCR and immunohistochemistry. Notch-1 AS mice were employed as a model of impaired Notch signalling in vivo. Experimental OA was induced by destabilisation of the medial meniscus (DMM). The extent of cartilage destruction and osteophyte formation was analysed by safranin-O staining with subsequent assessment of the Osteoarthritis Research Society International (OARSI) and Mankin scores and µCT scanning. Collagen X staining was used as a marker of chondrocyte hypertrophy. The role of hairy/enhancer of split 1 (Hes-1) was investigated with knockdown and overexpression experiments. Notch signalling was activated in human and murine OA with increased expression of Jagged1, Notch-1, accumulation of the Notch intracellular domain 1 and increased transcription of Hes-1. Notch1 AS mice showed exacerbated OA with increases in OARSI scores, osteophyte formation, increased subchondral bone plate density, collagen X and osteocalcin expression and elevated levels of Epas1 and ADAM-TS5 mRNA. Inhibition of the Notch pathway induced activation of hedgehog signalling with induction of Gli-1 and Gli-2 and increased transcription of hedgehog target genes. The regulatory effects of Notch signalling on Gli-expression were mimicked by Hes-1. Inhibition of Notch signalling activates hedgehog signalling, enhances chondrocyte hypertrophy and exacerbates experimental OA including osteophyte formation. These data suggest that the activation of the Notch pathway may limit aberrant hedgehog signalling in OA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  7. Combined Radial and Femoral Access Strategy and Radial-Femoral Rendezvous in Patients With Long and Complex Iliac Occlusions.

    Hanna, Elias B; Mogabgab, Owen N; Baydoun, Hassan

    2018-01-01

    We present cases of complex, calcified iliac occlusive disease revascularized via a combined radial-femoral access strategy. Through a 6-French, 125-cm transradial guiding catheter, antegrade guidewires and catheters are advanced into the iliac occlusion, while retrograde devices are advanced transfemorally. The transradial and transfemoral channels communicate, allowing the devices to cross the occlusion into the true lumen (radial-femoral antegrade-retrograde rendezvous).

  8. Estimated carotid-femoral pulse wave velocity has similar predictive value as measured carotid-femoral pulse wave velocity

    Greve, Sara V; Blicher, Marie K; Kruger, Ruan

    2016-01-01

    BACKGROUND: Carotid-femoral pulse wave velocity (cfPWV) adds significantly to traditional cardiovascular risk prediction, but is not widely available. Therefore, it would be helpful if cfPWV could be replaced by an estimated carotid-femoral pulse wave velocity (ePWV) using age and mean blood pres...... that these traditional risk scores have underestimated the complicated impact of age and blood pressure on arterial stiffness and cardiovascular risk....

  9. Femoral neck-shaft angle in extra-capsular proximal femoral fracture fixation; does it make a TAD of difference?

    Walton, N P; Wynn-Jones, H; Ward, M S; Wimhurst, J A

    2005-11-01

    The effect of femoral neck-shaft angle and implant type on the accuracy of lag screw placement in extra-capsular proximal femoral fracture fixation was investigated. Radiographs of all extra-capsular proximal femoral fractures seen in one unit over 18 months were reviewed. Of 399 cases, 307 (237 female, 70 male) were included in the study as they had no contra-lateral proximal femoral metal work. Femoral neck-shaft angle (NSA) of the uninjured hip and magnification adjusted tip-apex distance (TAD) of femoral head lag screw were measured. Type of fixation implant was 135 degrees classic hip screw (CHS) (n=144) or 130 degrees intra-medullary hip screw (IMHS) (n=163). Mean contra-lateral NSA was 130.2 degrees (112.9--148 degrees ) and 64 patients (58 female, 6 male) had a NSA TAD was 18.7 mm (5.8--43.8mm) and 88.9% of cases had a TAD of less than 25 mm. TAD values were significantly greater using an IMHS if NSA was 125 degrees (p=0.028). This was not the case with the CHS. The use of the 130 degrees -IMHS in patients with a NSA 125 degrees and caution is advocated when using this device in such cases.

  10. Expression of Notch1 Correlates with Breast Cancer Progression and Prognosis.

    Xun Yuan

    Full Text Available Various studies have evaluated the significance of Notch1 expression in breast cancer, but the results have ever been disputed. By using 21 studies involving 3867 patients, this meta-analysis revealed that the expression of Notch1 was significantly higher in breast cancer than in normal tissues (OR=7.21; 95%CI, 4.7-11.07 and that higher Notch1 expression was associated with transition from ductal carcinoma in situ (DCIS to invasive cancer (OR=3.75; 95% CI, 1.8-7.78. Higher Notch1 activity was observed in the basal subtype of breast cancer (OR=2.53; 95% CI, 1.18-5.43. Moreover, patients with Notch1 overexpression exhibited significantly worse overall and recurrence-free survival. Our meta-analysis suggests that Notch inhibitors may be useful in blocking the early progression of DCIS and that the outcomes of clinical trials for Notch1-targeting therapeutics could be improved by the molecular stratification of breast cancer patients.

  11. Asymmetric cell division and Notch signaling specify dopaminergic neurons in Drosophila.

    Murni Tio

    Full Text Available In Drosophila, dopaminergic (DA neurons can be found from mid embryonic stages of development till adulthood. Despite their functional involvement in learning and memory, not much is known about the developmental as well as molecular mechanisms involved in the events of DA neuronal specification, differentiation and maturation. In this report we demonstrate that most larval DA neurons are generated during embryonic development. Furthermore, we show that loss of function (l-o-f mutations of genes of the apical complex proteins in the asymmetric cell division (ACD machinery, such as inscuteable and bazooka result in supernumerary DA neurons, whereas l-o-f mutations of genes of the basal complex proteins such as numb result in loss or reduction of DA neurons. In addition, when Notch signaling is reduced or abolished, additional DA neurons are formed and conversely, when Notch signaling is activated, less DA neurons are generated. Our data demonstrate that both ACD and Notch signaling are crucial mechanisms for DA neuronal specification. We propose a model in which ACD results in differential Notch activation in direct siblings and in this context Notch acts as a repressor for DA neuronal specification in the sibling that receives active Notch signaling. Our study provides the first link of ACD and Notch signaling in the specification of a neurotransmitter phenotype in Drosophila. Given the high degree of conservation between Drosophila and vertebrate systems, this study could be of significance to mechanisms of DA neuronal differentiation not limited to flies.

  12. Rapid measurement of auditory filter shape in mice using the auditory brainstem response and notched noise.

    Lina, Ioan A; Lauer, Amanda M

    2013-04-01

    The notched noise method is an effective procedure for measuring frequency resolution and auditory filter shapes in both human and animal models of hearing. Briefly, auditory filter shape and bandwidth estimates are derived from masked thresholds for tones presented in noise containing widening spectral notches. As the spectral notch widens, increasingly less of the noise falls within the auditory filter and the tone becomes more detectible until the notch width exceeds the filter bandwidth. Behavioral procedures have been used for the derivation of notched noise auditory filter shapes in mice; however, the time and effort needed to train and test animals on these tasks renders a constraint on the widespread application of this testing method. As an alternative procedure, we combined relatively non-invasive auditory brainstem response (ABR) measurements and the notched noise method to estimate auditory filters in normal-hearing mice at center frequencies of 8, 11.2, and 16 kHz. A complete set of simultaneous masked thresholds for a particular tone frequency were obtained in about an hour. ABR-derived filter bandwidths broadened with increasing frequency, consistent with previous studies. The ABR notched noise procedure provides a fast alternative to estimating frequency selectivity in mice that is well-suited to high through-put or time-sensitive screening. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Reduced Notch signalling leads to postnatal skeletal muscle hypertrophy in Pofut1cax/cax mice.

    Al Jaam, Bilal; Heu, Katy; Pennarubia, Florian; Segelle, Alexandre; Magnol, Laetitia; Germot, Agnès; Legardinier, Sébastien; Blanquet, Véronique; Maftah, Abderrahman

    2016-09-01

    Postnatal skeletal muscle growth results from the activation of satellite cells and/or an increase in protein synthesis. The Notch signalling pathway maintains satellite cells in a quiescent state, and once activated, sustains their proliferation and commitment towards differentiation. In mammals, POFUT1-mediated O-fucosylation regulates the interactions between NOTCH receptors and ligands of the DELTA/JAGGED family, thus initiating the activation of canonical Notch signalling. Here, we analysed the consequences of downregulated expression of the Pofut1 gene on postnatal muscle growth in mutant Pofut1(cax/cax) (cax, compact axial skeleton) mice and differentiation of their satellite cell-derived myoblasts (SCDMs). Pofut1(cax/cax) mice exhibited muscle hypertrophy, no hyperplasia and a decrease in satellite cell numbers compared with wild-type C3H mice. In agreement with these observations, Pofut1(cax/cax) SCDMs differentiated earlier concomitant with reduced Pax7 expression and decrease in PAX7(+)/MYOD(-) progenitor cells. In vitro binding assays showed a reduced interaction of DELTA-LIKE 1 ligand (DLL1) with NOTCH receptors expressed at the cell surface of SCDMs, leading to a decreased Notch signalling as seen by the quantification of cleaved NICD and Notch target genes. These results demonstrated that POFUT1-mediated O-fucosylation of NOTCH receptors regulates myogenic cell differentiation and affects postnatal muscle growth in mice. © 2016 The Authors.

  14. Endocardial to myocardial notch-wnt-bmp axis regulates early heart valve development.

    Yidong Wang

    Full Text Available Endocardial to mesenchymal transformation (EMT is a fundamental cellular process required for heart valve formation. Notch, Wnt and Bmp pathways are known to regulate this process. To further address how these pathways coordinate in the process, we specifically disrupted Notch1 or Jagged1 in the endocardium of mouse embryonic hearts and showed that Jagged1-Notch1 signaling in the endocardium is essential for EMT and early valvular cushion formation. qPCR and RNA in situ hybridization assays reveal that endocardial Jagged1-Notch1 signaling regulates Wnt4 expression in the atrioventricular canal (AVC endocardium and Bmp2 in the AVC myocardium. Whole embryo cultures treated with Wnt4 or Wnt inhibitory factor 1 (Wif1 show that Bmp2 expression in the AVC myocardium is dependent on Wnt activity; Wnt4 also reinstates Bmp2 expression in the AVC myocardium of endocardial Notch1 null embryos. Furthermore, while both Wnt4 and Bmp2 rescue the defective EMT resulting from Notch inhibition, Wnt4 requires Bmp for its action. These results demonstrate that Jagged1-Notch1 signaling in endocardial cells induces the expression of Wnt4, which subsequently acts as a paracrine factor to upregulate Bmp2 expression in the adjacent AVC myocardium to signal EMT.

  15. Notch1 regulates hippocampal plasticity through interaction with the Reelin pathway, glutamatergic transmission and CREB signaling

    Emanuele eBrai

    2015-11-01

    Full Text Available Notch signaling plays a crucial role in adult brain function such as synaptic plasticity, memory and olfaction. Several reports suggest an involvement of this pathway in neurodegenerative dementia. Yet, to date, the mechanism underlying Notch activity in mature neurons remains unresolved. In this work, we investigate how Notch regulates synaptic potentiation and contributes to the establishment of memory in mice. We observe that Notch1 is a postsynaptic receptor with functional interactions with the Reelin receptor, ApoER2, and the ionotropic receptor, NMDAR. Targeted loss of Notch1 in the hippocampal CA fields affects Reelin signaling by influencing Dab1 expression and impairs the synaptic potentiation achieved through Reelin stimulation. Further analysis indicates that loss of Notch1 affects the expression and composition of the NMDAR but not AMPAR. Glutamatergic signaling is further compromised through downregulation of CamKII and its secondary and tertiary messengers resulting in reduced CREB signaling. Our results identify Notch1 as an important regulator of mechanisms involved in synaptic plasticity and memory formation. These findings emphasize the possible involvement of this signaling receptor in dementia.

  16. Evidence of Aortopathy in Mice with Haploinsufficiency of Notch1 in Nos3-Null Background

    Sara N. Koenig

    2015-03-01

    Full Text Available Thoracic aortic aneurysms (TAA are a significant cause of morbidity and mortality in humans. While the exact etiology is unknown, genetic factors play an important role. Mutations in NOTCH1 have been linked to bicuspid aortic valve (BAV and aortopathy in humans. The aim of this study was to determine if haploinsufficiency of Notch1 contributes to aortopathy using Notch1+/−; Nos3−/− mice. Echocardiographic analysis of Notch1+/−; Nos3−/− mice reveals effacement of the sinotubular junction and a trend toward dilation of the aortic sinus. Furthermore, examination of the proximal aorta of Notch1+/−; Nos3−/− mice reveals elastic fiber degradation, a trend toward increased matrix metalloproteinase 2 expression, and increased smooth muscle cell apoptosis, features characteristic of aneurysmal disease. Although at a lower penetrance, we also found features consistent with aortopathic changes in Notch1 heterozygote mice and in Nos3-null mice. Our findings implicate a novel role for Notch1 in aortopathy of the proximal aorta.

  17. Electroacupuncture pretreatment induces tolerance against focal cerebral ischemia through activation of canonical Notch pathway

    Zhao Yu

    2012-09-01

    Full Text Available Abstract Background Electroacupuncture (EA pretreatment can induce the tolerance against focal cerebral ischemia. However, the underlying mechanisms have not been fully understood. Emerging evidences suggest that canonical Notch signaling may be involved in ischemic brain injury. In the present study, we tested the hypothesis that EA pretreatment-induced tolerance against focal cerebral ischemia is mediated by Notch signaling. Results EA pretreatment significantly enhanced Notch1, Notch4 and Jag1 gene transcriptions in the striatum, except Notch1 intracellular domain level, which could be increased evidently by ischemia. After ischemia and reperfusion, Hes1 mRNA and Notch1 intracellular domain level in ischemic striatum in EA pretreatment group were increased and reached the peak at 2 h and 24 h, respectively, which were both earlier than the peak achieved in control group. Intraventricular injection with the γ-secretase inhibitor MW167 attenuated the neuroprotective effect of EA pretreatment. Conclusions EA pretreatment induces the tolerance against focal cerebral ischemia through activation of canonical Notch pathway.

  18. Identification of a Paralog-Specific Notch1 Intracellular Domain Degron

    Matthew R. Broadus

    2016-05-01

    Full Text Available Upon Notch pathway activation, the receptor is cleaved to release the Notch intracellular domain (NICD, which translocates to the nucleus to activate gene transcription. Using Xenopus egg extracts, we have identified a Notch1-specific destruction signal (N1-Box. We show that mutations in the N1-Box inhibit NICD1 degradation and that the N1-Box is transferable for the promotion of degradation of heterologous proteins in Xenopus egg extracts and in cultured human cells. Mutation of the N1-Box enhances Notch1 activity in cultured human cells and zebrafish embryos. Human cancer mutations within the N1-Box enhance Notch1 signaling in transgenic zebrafish, highlighting the physiological relevance of this destruction signal. We find that binding of the Notch nuclear factor, CSL, to the N1-Box blocks NICD1 turnover. Our studies reveal a mechanism by which degradation of NICD1 is regulated by the N1-Box to minimize stochastic flux and to establish a threshold for Notch1 pathway activation.

  19. Notch Signaling Pathway Is Activated in Motoneurons of Spinal Muscular Atrophy

    Gabriel Olmos

    2013-05-01

    Full Text Available Spinal muscular atrophy (SMA is a neurodegenerative disease produced by low levels of Survival Motor Neuron (SMN protein that affects alpha motoneurons in the spinal cord. Notch signaling is a cell-cell communication system well known as a master regulator of neural development, but also with important roles in the adult central nervous system. Aberrant Notch function is associated with several developmental neurological disorders; however, the potential implication of the Notch pathway in SMA pathogenesis has not been studied yet. We report here that SMN deficiency, induced in the astroglioma cell line U87MG after lentiviral transduction with a shSMN construct, was associated with an increase in the expression of the main components of Notch signaling pathway, namely its ligands, Jagged1 and Delta1, the Notch receptor and its active intracellular form (NICD. In the SMNΔ7 mouse model of SMA we also found increased astrocyte processes positive for Jagged1 and Delta1 in intimate contact with lumbar spinal cord motoneurons. In these motoneurons an increased Notch signaling was found, as denoted by increased NICD levels and reduced expression of the proneural gene neurogenin 3, whose transcription is negatively regulated by Notch. Together, these findings may be relevant to understand some pathologic attributes of SMA motoneurons.

  20. Fatigue damage mechanics of notched graphite-epoxy laminates

    Spearing, Mark; Beaumont, Peter W. R.; Ashby, Michael F.

    A modeling approach is presented that recognizes that the residual properties of composite laminates after any form of loading depend on the damage state. Therefore, in the case of cyclic loading, it is necessary to first derive a damage growth law and then relate the residual properties to the accumulated damage. The propagation of fatigue damage in notched laminates is investigated. A power law relationship between damage growth and the strain energy release rate is developed. The material constants used in the model have been determined in independent experiments and are invariant for all the layups investigated. The strain energy release rates are calculated using a simple finite element representation of the damaged specimen. The model is used to predict the effect of tension-tension cyclic loading on laminates of the T300/914C carbon-fiber epoxy system. The extent of damage propagation is successfully predicted in a number of cross-ply laminates.

  1. Self-collimation-based photonic crystal notch filters

    Lee, Sun-Goo; Kim, Seong-Han; Kee, Chul-Sik; Kim, Kap-Joong

    2017-01-01

    We introduce a design concept of an optical notch filter (NF) utilizing two perfectly reflecting mirrors and a beam splitter. Based on the new design concept, a photonic crystal (PC)-NF based on the self-collimation phenomenon in a two-dimensional PC is proposed and studied through finite-difference time-domain simulations and experimental measurements in a microwave region. The transmission properties of the self-collimation-based PC-NF were demonstrated to be controlled by adjusting the values of parameters such as the radius of rods in the line-defect beam splitter, distance between the two perfectly reflecting mirrors, and radius of rods on the outermost surface of the perfectly reflecting mirrors. Our results indicate that the proposed design concept could provide a new approach to manipulate light propagation, and the PC-NF could increase the applicability of the self-collimation phenomenon in a PC. (paper)

  2. Simplified elastoplastic methods of analysing fatigue in notches

    Autrusson, B.

    1993-01-01

    The aim of this study is to show the state of the art concerning methods of mechanical analysis available in the literature for evaluating notch root elastoplastic strain. The components of fast breeder reactors are subjected to numerous thermal transients, which can cause fatigue failure. To prevent this from happening, it is necessary to know the local strain range and to use it to estimate the number of cycles to crack initiation. Practical methods have been developed for the calculation of the local strain range, and have led to the drafting of design rules. Direct methods of determining the local strain range of the 'inelastic analysis' type have also been described. In conclusion a series of recommendations is made on the applicability and the conservatism of these methods

  3. Prevention of excessive postoperative sliding of the short femoral nail in femoral trochanteric fractures.

    Ito, Juji; Takakubo, Yuya; Sasaki, Kan; Sasaki, Junya; Owashi, Kazuya; Takagi, Michiaki

    2015-05-01

    Lag screw cut-out is one of the major postoperative complications on femoral trochanteric fractures. However, precise analyses of excessive sliding and lag screw cut-out were limited. The purpose of this study was to investigate the factors that induce this unfavorable event. From April 2010 to April 2013, 226 patients were operated in our institute using a short femoral nail. Among them, 177 patients (29 males and 148 females) with a mean age of 84 years (60-97 years), who were followed up >3 months, were included in this study. The postoperative sliding distance, fracture type (AO/OTA classification), tip-apex distance (TAD), reduction pattern in the postoperative X-ray (antero-posterior and lateral views), bone quality (canal flare and cortical indices), walking ability at the time of pre-injury and final follow-up, and complications were investigated retrospectively. The mean sliding distance was 3.7 mm, and one cut-out case (0.6 %) was observed. The sliding distance of the AO/OTA 31-A2 fractures was significantly longer than that of the A1 fractures (p fractures, an accurate reduction in the lateral view at surgery is important, particularly in unstable fractures.

  4. Multiplanar CT assessment of femoral head displacement in slipped capital femoral epiphysis

    Monazzam, Shafagh [Rady Children' s Hospital and Health Center, Department of Orthopedics, San Diego, CA (United States); Dwek, Jerry R. [Rady Children' s Hospital and Health Center, Department of Radiology, San Diego, CA (United States); Hosalkar, Harish S. [Center for Hip Preservation, Department of Orthopedic Surgery, TriCity Medical Center, Oceanside, CA (United States)

    2013-12-15

    With recent changing approaches to the management of slipped capital femoral epiphysis (SCFE), the accurate radiographic assessment of maximum extent of displacement is crucial for planning surgical treatment. To determine what plane best represents the maximum SCFE displacement as quantified by the head-neck angle difference (HNAD), whether HNAD can quantitatively differentiate the SCFE cohort from the normal cohort, based on CT, and how Southwick slip angle (SSA) compares to HNAD. We reviewed 19 children with SCFE (23 affected hips) with preoperative CT scans and 27 age- and sex-matched children undergoing abdominal CT for non-orthopedic problems. Head-neck angle (HNA), the angle between the femoral epiphysis and the neck axis, was measured in three planes on each hip and the HNAD (affected - unaffected hip) was determined. SSA was measured on radiographs. The coronal HNAD (mean 8.7 ) was less than both the axial-oblique (mean 30.7 ) and sagittal (mean 37.4 ) HNADs, which were also greater than the HNADs of the normal cohort. Grouping HNAD measurements by SSA severity classification did not consistently distinguish between SCFE severity levels. Axial-oblique and sagittal planes best represent the maximum SCFE displacement while biplanar radiograph may underestimate the extent of the displacement, thereby potentially altering the management between in situ pinning and capital realignment. (orig.)

  5. A Novel Notch-YAP Circuit Drives Stemness and Tumorigenesis in Embryonal Rhabdomyosarcoma.

    Slemmons, Katherine K; Crose, Lisa E S; Riedel, Stefan; Sushnitha, Manuela; Belyea, Brian; Linardic, Corinne M

    2017-12-01

    Rhabdomyosarcoma (RMS), a cancer characterized by skeletal muscle features, is the most common soft-tissue sarcoma of childhood. While low- and intermediate-risk groups have seen improved outcomes, high-risk patients still face a 5-year survival rate of statistic that has not changed in over 40 years. Understanding the biologic underpinnings of RMS is critical. The developmental pathways of Notch and YAP have been identified as potent but independent oncogenic signals that support the embryonal variant of RMS (eRMS). Here, the cross-talk between these pathways and the impact on eRMS tumorigenesis is reported. Using human eRMS cells grown as three-dimensional (3D) rhabdospheres, which enriches in stem cells, it was found that Notch signaling transcriptionally upregulates YAP1 gene expression and YAP activity. Reciprocally, YAP transcriptionally upregulates the Notch ligand genes JAG1 and DLL1 and the core Notch transcription factor RBPJ This bidirectional circuit boosts expression of key stem cell genes, including SOX2 , which is functionally required for eRMS spheres. Silencing this circuit for therapeutic purposes may be challenging, because the inhibition of one node (e.g., pharmacologic Notch blockade) can be rescued by upregulation of another (constitutive YAP expression). Instead, dual inhibition of Notch and YAP is necessary. Finally, supporting the existence of this circuit beyond a model system, nuclear Notch and YAP protein expression are correlated in human eRMS tumors, and YAP suppression in vivo decreases Notch signaling and SOX2 expression. Implications: This study identifies a novel oncogenic signaling circuit driving eRMS stemness and tumorigenesis, and provides evidence and rationale for combination therapies co-targeting Notch and YAP. Mol Cancer Res; 15(12); 1777-91. ©2017 AACR . ©2017 American Association for Cancer Research.

  6. Notch Signaling Is Associated With ALDH Activity And An Aggressive Metastatic Phenotype In Murine Osteosarcoma Cells

    Xiaodong eMu

    2013-06-01

    Full Text Available Osteosarcoma (OS is the most common primary malignancy of bone, and pulmonary metastatic disease accounts for nearly all mortality. However, little is known about the biochemical signaling alterations that drive the progression of metastatic disease. Two murine OS cell populations, K7M2 and K12, are clonally related but differ significantly in their metastatic phenotypes and therefore represent excellent tools for studying metastatic OS molecular biology. K7M2 cells are highly metastatic, whereas K12 cells display limited metastatic potential. Here we report that the expression of Notch genes (Notch1, 2, 4 are up-regulated, including downstream targets Hes1 and Stat3, in the highly metastatic K7M2 cells compared to the less metastatic K12 cells, indicating that the Notch signaling pathway is more active in K7M2 cells. We have previously described that K7M2 cells exhibit higher levels of aldehyde dehydrogenase (ALDH activity. Here we report that K7M2 cell ALDH activity is reduced with Notch inhibition, suggesting that ALDH activity may be regulated in part by the Notch pathway. Notch signaling is also associated with increased resistance to oxidative stress, migration, invasion, and VEGF expression in vitro. However, Notch inhibition did not significantly alter K7M2 cell proliferation. In conclusion, we provide evidence that Notch signaling is associated with ALDH activity and increased metastatic behavior in OS cells. Both Notch and ALDH are putative molecular targets for the treatment and prevention of OS metastasis.

  7. Second generation γ-secretase modulators exhibit different modulation of Notch β and Aβ production.

    Wanngren, Johanna; Ottervald, Jan; Parpal, Santiago; Portelius, Erik; Strömberg, Kia; Borgegård, Tomas; Klintenberg, Rebecka; Juréus, Anders; Blomqvist, Jenny; Blennow, Kaj; Zetterberg, Henrik; Lundkvist, Johan; Rosqvist, Susanne; Karlström, Helena

    2012-09-21

    The γ-secretase complex is an appealing drug target when the therapeutic strategy is to alter amyloid-β peptide (Aβ) aggregation in Alzheimer disease. γ-Secretase is directly involved in Aβ formation and determines the pathogenic potential of Aβ by generating the aggregation-prone Aβ42 peptide. Because γ-secretase mediates cleavage of many substrates involved in cell signaling, such as the Notch receptor, it is crucial to sustain these pathways while altering the Aβ secretion. A way of avoiding interference with the physiological function of γ-secretase is to use γ-secretase modulators (GSMs) instead of inhibitors of the enzyme. GSMs modify the Aβ formation from producing the amyloid-prone Aβ42 variant to shorter and less amyloidogenic Aβ species. The modes of action of GSMs are not fully understood, and even though the pharmacology of GSMs has been thoroughly studied regarding Aβ generation, knowledge is lacking about their effects on other substrates, such as Notch. Here, using immunoprecipitation followed by MALDI-TOF MS analysis, we found that two novel, second generation GSMs modulate both Notch β and Aβ production. Moreover, by correlating S3-specific Val-1744 cleavage of Notch intracellular domain (Notch intracellular domain) to total Notch intracellular domain levels using immunocytochemistry, we also demonstrated that Notch intracellular domain is not modulated by the compounds. Interestingly, two well characterized, nonsteroidal anti-inflammatory drugs (nonsteroidal anti-inflammatory drug), R-flurbiprofen and sulindac sulfide, affect only Aβ and not Notch β formation, indicating that second generation GSMs and nonsteroidal anti-inflammatory drug-based GSMs have different modes of action regarding Notch processing.

  8. Immunohistochemical expression of Notch signaling in the lining epithelium of periapical cysts.

    Meliou, Eleni; Kerezoudis, Nikolaos; Tosios, Konstantinos; Lafkas, Daniel; Kiaris, Hippokratis

    2011-02-01

    In this study we evaluated the immunohistochemical expression of the receptors Notch 1 and Notch 2, the ligand Delta 1, and the transcription factors HES 1 and HES 5 in the epithelium of well-defined periapical cysts. Immunohistochemistry was carried out on 55 formalin-fixed and paraffin-embedded, well-defined periapical cysts with minimum inflammation, obtained from the archival tissue database of the Department of Oral Pathology and Surgery. Western blotting was performed to evaluate the specificity of the anti-Notch antibody and the expression of Notch signaling in 5 fresh-frozen periapical cysts. The levels of staining intensity were estimated by the performance of a semiautomated image analysis system. Descriptive statistic of mean values obtained by computerized image analysis method was performed. Immunostaining reaction of all Notch signaling components was observed in the cytoplasm and/or the cytoplasmic membrane in the majority of epithelial cells of periapical cysts. Nuclear staining was observed occasionally in all cases. Notch 2 showed strong staining in 52.83% of the cases, followed by Notch 1 (35.85%), HES 1 and HES 5 moderate staining in 72.73% and 57.69% of the cases, respectively, and Delta 1 weak staining in 58.33% of the cases. No statistical correlation was found between the antibodies and the sex or the age of the study group. Notch is an evolutionarily conserved signaling mechanism that regulates cell fate decisions during development and postnatal life in organisms as diverse as worms, flies, and humans. The present observations indicate that Notch pathway is active downstream in the lining epithelium of periapical cysts, suggesting an involvement of this pathway in periapical cyst growth and expansion. Copyright © 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  9. The effect of shot peening on notched low cycle fatigue

    Soady, K.A.; Mellor, B.G.; Shackleton, J.; Morris, A.; Reed, P.A.S.

    2011-01-01

    Highlights: → Shot peening improves notched component three point bend low cycle fatigue life. → Notch shape does not affect the efficacy of the peening process. → Strain hardening and residual stress effects need separate consideration. → Loading direction residual stresses do not relax under bend load. - Abstract: The improvement in low cycle fatigue life created by shot peening ferritic heat resistant steel was investigated in components of varying geometries based on those found in conventional power station steam turbine blades. It was found that the shape of the component did not affect the efficacy of the shot peening process, which was found to be beneficial even under the high stress amplitude three point bend loads applied. Furthermore, by varying the shot peening process parameters and considering fatigue life it has been shown that the three surface effects of shot peening; roughening, strain hardening and the generation of a compressive residual stress field must be included in remnant life models as physically separate entities. The compressive residual stress field during plane bending low cycle fatigue has been experimentally determined using X-ray diffraction at varying life fractions and found to be retained in a direction parallel to that of loading and to only relax to 80% of its original magnitude in a direction orthogonal to loading. This result, which contributes to the retention of fatigue life improvement in low cycle fatigue conditions, has been discussed in light of the specific stress distribution applied to the components. The ultimate aim of the research is to apply these results in a life assessment methodology which can be used to justify a reduction in the length of scheduled plant overhauls. This will result in significant cost savings for the generating utility.

  10. Constitutively active Notch1 induces growth arrest of HPV-positive cervical cancer cells via separate signaling pathways

    Talora, Claudio; Cialfi, Samantha; Segatto, Oreste; Morrone, Stefania; Kim Choi, John; Frati, Luigi; Paolo Dotto, Gian; Gulino, Alberto; Screpanti, Isabella

    2005-01-01

    Notch signaling plays a key role in cell-fate determination and differentiation in different organisms and cell types. Several reports suggest that Notch signaling may be involved in neoplastic transformation. However, in primary keratinocytes, Notch1 can function as a tumor suppressor. Similarly, in HPV-positive cervical cancer cells, constitutively active Notch1 signaling was found to cause growth suppression. Activated Notch1 in these cells represses viral E6/E7 expression through AP-1 down-modulation, resulting in increased p53 expression and a block of pRb hyperphosphorylation. Here we show that in cervical cancer cell lines in which Notch1 ability to repress AP-1 activity is impaired, Notch1-enforced expression elicits an alternative pathway leading to growth arrest. Indeed, activated Notch1 signaling suppresses activity of the helix-loop-helix transcription factor E47, via ERK1/2 activation, resulting in inhibition of cell cycle progression. Moreover, we found that RBP-Jκ-dependent Notch signaling is specifically repressed in cervical cancer cells and this repression could provide one such mechanism that needs to be activated for cervical carcinogenesis. Finally, we show that inhibition of endogenous Notch1 signaling, although results in a proliferative advantage, sensitizes cervical cancer cell lines to drug-induced apoptosis. Together, our results provide novel molecular insights into Notch1-dependent growth inhibitory effects, counteracting the transforming potential of HPV

  11. Limit load and fully plastic stress analysis for circular notched plates and bars using fully plastic analysis

    Oh, Chang Kyun; Myung, Man Sik; Kim, Yun Jae; Park, Jin Moo

    2005-01-01

    For the last four decades, tension test of notched bars has been performed to investigate the effect of stress triaxiality on ductile fracture. To quantify the effect of the notch radius on stress triaxiality, the Bridgman equation is typically used. However, recent works based on detailed finite element analysis have shown that the Bridgman equation is not correct, possibly due to his assumption that strain is constant in the necked ligament. Up to present, no systematic work has been performed on fully plastic stress fields for notched bars in tension. This paper presents fully plastic results for tension of notched bars and plates in plane strain, via finite element limit analysis. The notch radius is systematically varied, covering both un-cracked and cracked cases. Comparison of plastic limit loads with existing solutions shows that existing solutions are accurate for notched plates, but not for notched bars. Accordingly new limit load solutions are given for notched bars. Variations of stress triaxiality with the notch radius and depth are also given, which again indicates that the Bridgman solution for notched bars is not correct and inaccuracy depends on the notch radius and depth

  12. Varus femoral osteotomy improves sphericity of the femoral head in older children with severe form of Legg-Calvé-Perthes disease.

    Terjesen, Terje; Wiig, Ola; Svenningsen, Svein

    2012-09-01

    In the Norwegian prospective study on Legg-Calvé-Perthes disease (LCPD), we found varus femoral osteotomy gave better femoral head sphericity at a mean of 5 years postoperative than physiotherapy in children older than 6.0 years at diagnosis with femoral head necrosis of more than 50%. That study did not include separate analyses for hips with 100% necrosis and those with a percentage of necrosis between 50% and 100%. We asked whether (1) femoral osteotomy improves femoral head sphericity at followup in all patients with more than 50% femoral head necrosis or in selected groups only and (2) there is a critical age between 6.0 and 10.0 years over which femoral osteotomy does not improve the prognosis. We treated 70 patients with unilateral LCPD, age at diagnosis of more than 6.0 years, and femoral head necrosis of more than 50% with varus femoral osteotomy between 1996 and 2000. We classified necrosis using the Catterall classification. We established a control group of 51 similar children who received physiotherapy. At the 5-year followup visit, the hips were graded according to femoral head shape: spherical, ovoid, or flat. At 5-year followup, there was no difference between the treatment groups in radiographic outcome in Catterall Group 3 hips. In Catterall Group 4 hips, femoral head sphericity was better in the osteotomy group, with flat femoral heads in 14% compared to 75% after physiotherapy. The same trend toward better head sphericity occurred when the lateral pillar classification was used. In children aged 6.0 to 10.0 years, in whom the whole femoral head is affected, femoral head sphericity 5 years after femoral osteotomy was better than that after physiotherapy.

  13. [Femoral artery pseudoaneurysms encountered in orthopedics and traumatology].

    Raherinantenaina, F; Rajaonanahary, T M A; Rakoto Ratsimba, H N

    2015-12-01

    Most published articles regarding orthopedic- and trauma-related femoral artery pseudoaneurysms (FAPs) are case reports in English. Reported cases are often associated with a literature review but actually provide little robust data. We wanted to summarize the current knowledge on diagnostic and therapeutic features of these FAPs. A new case of superficial FAP is described followed by a review of the literature. A bibliographic search was performed online (PubMed, ScinceDirect) from 1964 to 2015 using the descriptors "traumatic femoral pseudoaneurysm, orthopedic surgery, osteochondroma". A total of 64 cases of FAPs was analyzed. There were 50 men with an average age of 40.72±26.45 years old. The most common clinical presentation was painful swelling (34%). Arteriography was the commonest radiological investigation used (63%). The main etiologies were orthopedic injuries (47%), surgery of the upper thigh (30%) and femoral osteochondromas (23%). Arterial injuries included superficial femoral (47%) and profunda femoris artery (50%). The treatment was open surgery (56%) or endovascular repair (36%). Deep femoral artery and its branches were embolized (47%) or ligated (38%). Endovascular stenting was performed in 30% of posttraumatic FAPs. All FAPs relating to osteochondromas were repaired surgically. Postoperative courses were uneventful in 95% of patients. Endovascular embolization is preferred in management of postsurgical FAPs which have usually involved the deep femoral artery. Endovascular stenting graft may be proposed for posttraumatic FAPs, for which the superficial femoral trunk is the most often involved vessel. Surgical repair should be performed when endovascular stenting graft is not feasible. Surgical repair is mandatory for all FAPs secondary to traumatic exostoses. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  14. Structural and functional studies of bioobjects prepared from femoral heads

    Kirilova, I. A., E-mail: IKirilova@niito.ru; Podorozhnaya, V. T., E-mail: VPodorognaya@niito.ru [Research Institute of Traumatology and Orthopedics n.a. Ya.L. Tsivyan, 17, Frunze, Novosibirsk, 630091 (Russian Federation); Sharkeev, Yu. P., E-mail: sharkeev@ispms.tsc.ru [Institute of Strength Physics and Materials Science SB RAS, 2/4, pr. Akademicheskii, Tomsk, 634021 (Russian Federation); National Research Tomsk Polytechnic University, 30, Lenin Avenue, Tomsk, 634050 (Russian Federation); Popova, K. S., E-mail: kseniya@ispms.tsc.ru; Uvarkin, P. V., E-mail: uvarkin@ispms.tsc.ru [Institute of Strength Physics and Materials Science SB RAS, 2/4, pr. Akademicheskii, Tomsk, 634021 (Russian Federation)

    2015-11-17

    Results of examination of physicomechanical characteristics of samples of medial femoral head cuts are presented. The samples of medial femoral head cuts resected in 6 patients with coxarthrosis in primary endoprosthetic replacement of a coxofemoral joint have been tested for micro- and nanohardness. Young’s modulus and elemental composition of bone tissue have been investigated. To estimate the architectonics of cancellous tissue of the femoral head, adjacent cuts of the same patient have been analyzed. The porosity of bone tissue was estimated from macroscopic images obtained using macrophotography. The total porosity is calculated as the ratio of the total length of straight line segments overlapping pores to the total length of secants. A three-point bending test of the samples has shown that their strength changed from 0.187 to 1.650 MPa and their elasticity modulus changes from 1.69 to 8.15 MPa. The microhardness of the samples changes in the range 220–265 MPa and the average microhardness of medial femoral head cuts is 240 MPa. The elemental composition of medial femoral head cuts is represented by basic Ca, P, O, Na and Mg elements as well as by Sn, S, Fe, Cr, and C in microamounts. The atomic Ca to P ratio for bone tissue is 1.55. It is revealed that pores of the upper part of the femoral head have a more regular shape and in the lower part they are more elongated along the cut and occupy a larger volume. The lower part of the femoral head has a higher porosity (39 and 33%) than the upper part (34 and 30%). The total porosity of all samples does not exceed 37%.

  15. Radiological assessment of the femoral bowing in Japanese population

    Abdelaal Ahmed Hamed Kassem

    2016-01-01

    Full Text Available Introduction: Differences in the magnitude of bowing between races are well-known characteristics of the femur. Asian races have an increased magnitude of femoral bowing but most of the orthopedic implants designed for the femur do not match this exaggerated bowing. We calculated the sagittal and coronal femoral bowing in the Japanese population at different levels of the femur and addressed its surgical significance. Material and methods: We calculated the sagittal and coronal bowing of 132 Japanese femora using CT scan of the femur. A mathematical calculation of the radius of curvature at proximal, middle, and distal regions of the femur was used to determine the degree of femoral bowing. Results: Mean sagittal bowing of the femur was 581, 188, and 161 mm for the proximal, middle, and distal thirds of the femur and mean lateral bowing was 528, 5092, and 876 mm, respectively. Mean sagittal and coronal bowing for the whole femur was 175 and 2640 mm, respectively. No correlation was found between age, gender, length of femur, and the degree of bowing. Conclusion: Our study reveals that femoral bowing in the Japanese population is 175 mm in the sagittal plane and 2640 mm in the coronal plane; these values are greater than the femoral bowing in other ethnic groups studied in the literature. This may result in varying degrees of mismatch between the western-manufactured femoral intramedullary implants and the Japanese femur. We recommend that orthopedic surgeons to accurately perform preoperative evaluation of the femoral bowing to avoid potential malalignment, rotation, and abnormal stresses between the femur and implant.

  16. Femoral Condyle Fracture during Anterior Cruciate Ligament Reconstruction

    Selahattin Ozyurek

    2015-07-01

    Full Text Available Dear Editor,We have greatly enjoyed reading the case report entitled “‘Femoral Condyle Fracture during Revision of Anterior Cruciate Ligament Reconstruction: Case Report and a Review of Literature in the issue of Arch Bone Jt Surg. 2015;3(2 with great interest. We would like to commend the authors for their detailed and valuable work. Although various case reports have described postoperative distal femur fracture at a range of time intervals (1,2 intraoperative intra-articular distal femur fracture is a unique entity.However, we believe that some important additional observations seem necessary to be contributed through this study. In this article, the authors stated that, to the best of their knowledge, there is no other case report in the literature introducing a femoral condyle fracture during arthroscopic ACL reconstruction or revision reconstruction. Nevertheless, we would like to call the attention of the readers to the fact that that the literature contains one additional case report re‌porting on intraoperative distal femoral coronal plane (Hoffa fracture during primary ACL reconstruction (2. Werner BC and Miller MD presented of case report of an intraoperative distal femoral coronal plane (Hoffa fracture that occurred during independent femoral tunnel drilling and dilation in a primary ACL reconstruction. As in the their case, this type of fracture can occur with appropriately placed femoral tunnels, but the risk can increase with larger graft diameters in patients with smaller lateral femoral condyles The patient was treated with open reduction and internal fixation, without compromise of graft stability and with good recovery of function. We believe that tailoring graft size to the size of the patient is important to prevent similar adverse events.

  17. Chondromalacia of trochlear notch after healing of olecranon stress fracture: a case report.

    Lu, Cheng-Chang; Chen, Shen-Kai; Wang, Chih-Wei; Chou, Pei-Hsi

    2006-05-01

    Chondromalacia of the trochlear notch and stress fracture of olecranon are uncommon injuries in the throwing athletes. We report an 18-year-old high school pitcher who had persistent postero-lateral elbow pain after a healed olecranon stress fracture of the right elbow. Diagnostic arthroscopy revealed chondromalacia of the trochlear notch. After treatment with arthroscopic drilling and abrasion chondroplasty, he returned to competitive pitching 1 year later postsurgery. This rare association between chondromalacia and stress fracture of the olecranon has not been reported previously in the literatures. Chondromalacia of the trochlear notch should be included as a differential diagnosis in evaluating athletes with persistent elbow pain after healed olecranon stress fractures.

  18. Identification of 11-amino acid peptides that disrupt Notch-mediated processes in Drosophila

    Yeh Hsiao-Fong

    2011-06-01

    Full Text Available Abstract Background The conserved Notch signaling pathway regulates cell fate decisions and maintains stem cells in multicellular organisms. Up-regulation of Notch signaling is observed in several types of cancer and is causally involved in proliferation and survival of cancer cells. Thus, it is of great interest to look for anti-Notch reagents for therapeutic purposes. In model animal Drosophila, Notch signaling restricts selection of sensory organ precursors (SOPs during external sensory (ES organ development. To look for novel genes that can suppress Notch signaling, we performed a gain-of-function modifier screen to look for genes that enhance the phenotype of ectopic ES organs induced by overexpression of phyllopod, a gene required for SOP specification. Results From the gain-of-function screen, we discovered that overexpression of polished rice/tarsal-less (pri/tal increases the numbers of ES organs as well as SOPs. pri/tal is a polycistronic gene that contains four short open reading frames encoding three 11-amino acid and one 32-amino acid peptides. Ectopic expression of the 11 amino-acid peptides recapitulates the pri/tal misexpression phenotype in ectopic ES organ formation. In situ hybridization experiment reveals that pri/tal mRNA is expressed in the SOPs of the chemosensory organs and the stretch-sensing chordotonal organs. In Drosophila wing development, the Notch signaling pathway mediates the formation of the dorsal-ventral (DV compartmental boundary and the restriction of the vein width from the primordial veins, the proveins. We also found that pri/tal mRNA is expressed in the DV boundary and the longitudinal proveins, and overexpression of Pri/Tal peptides disrupts the DV boundary formation and helps to expand the width of the wing vein. Genetic analyses further show that a Notch loss-of-function allele strongly enhances these two phenotypes. Cut and E(splmβ are target genes of the Notch pathway in DV boundary formation and

  19. Probabilistic fatigue life prediction methodology for notched components based on simple smooth fatigue tests

    Wu, Z. R.; Li, Z. X. [Dept.of Engineering Mechanics, Jiangsu Key Laboratory of Engineering Mechanics, Southeast University, Nanjing (China); Hu, X. T.; Xin, P. P.; Song, Y. D. [State Key Laboratory of Mechanics and Control of Mechanical Structures, Nanjing University of Aeronautics and Astronautics, Nanjing (China)

    2017-01-15

    The methodology of probabilistic fatigue life prediction for notched components based on smooth specimens is presented. Weakestlink theory incorporating Walker strain model has been utilized in this approach. The effects of stress ratio and stress gradient have been considered. Weibull distribution and median rank estimator are used to describe fatigue statistics. Fatigue tests under different stress ratios were conducted on smooth and notched specimens of titanium alloy TC-1-1. The proposed procedures were checked against the test data of TC-1-1 notched specimens. Prediction results of 50 % survival rate are all within a factor of two scatter band of the test results.

  20. Notch and hydrogen effects on sensitized 21-6-9 stainless steel

    Caskey, C.R. Jr.

    1979-01-01

    Type 21-6-9 stainless steel alloy is slightly notch sensitive in the solution annealed condition, a behavior that is aggravated by sensitization anneal at 920 0 K. The lower toughness of the sensitized alloy is a measure of microstructural embrittlement associated with carbide precipitation in grain boundaries. The tendency toward grain boundary fracture in the sensitized alloy is accentuated by stress concentration at the notch. Also, there is an increase in notch sensitivity when the alloy is tested in a high pressure (69 MPa) hydrogen environment, due to susceptibility of the grain boundaries to hydrogen embrittlement

  1. UWB Filtering Power Divider with Two Narrow Notch-bands and Wide Stop-band

    Wei, Feng; Wang, Xin-Yi; Zou, Xin Tong; Shi, Xiao Wei

    2017-12-01

    A compact filtering ultra-wideband (UWB) microstrip power divider (PD) with two sharply rejected notch-bands and wide stopband is analyzed and designed in this paper. The proposed UWB PD is based on a conventional Wilkinson power divider, while two stub loaded resonators (SLRs) are coupled into two symmetrical output ports to achieve a bandpass filtering response. The simplified composite right/left-handed (SCRLH) resonators are employed to generate the dual notched bands. Defected ground structure (DGS) is introduced to improve the passband performance. Good insertion/return losses, isolation and notch-band rejection are achieved as demonstrated in both simulation and experiment.

  2. Effects of Notch Introduction on 3-Point Bending Cutting Characteristics of Frozen Fish

    Hagura, Yoshio; Suzuki, Kanichi

    2002-01-01

    We have proposed a freeze cutting method in which a three point bending load is applied on a frozen fish body to cut in round slices. Lowering the three-point bending load can facilitate the freeze cutting processing. Based on the idea that a notch in the fish body may lower the cutting load, the effect of introducing a notch was examined with respect to cutting stress and smoothness of cut surface in model fish meat and in saury. It was found that the introduced notch effectively lowered the...

  3. Identification of a Paralog-Specific Notch1 Intracellular Domain Degron

    Broadus, Matthew R.; Chen, Tony W.; Neitzel, Leif R.; Ng, Victoria H.; Jodoin, Jeanne; Lee, Laura A.; Salic, Adrian; Robbins, David J.; Capobianco, Anthony J.; Patton, James G.; Huppert, Stacey S.; Lee, Ethan

    2016-01-01

    Upon Notch pathway activation, the receptor is cleaved to release the Notch intracellular domain (NICD), which translocates to the nucleus to activate gene transcription. Using Xenopus egg extracts, we have identified a Notch1-specific destruction signal (N1-Box). We show that mutations in the N1-Box inhibit NICD1 degradation and that the N1-Box is transferable for the promotion of degradation of heterologous proteins in Xenopus egg extracts and in cultured human cells. Mutation of the N1-Box...

  4. Thermally induced high frequency random amplitude fatigue damage at sharp notches

    Lewis, M.W.J.

    1992-01-01

    Experiments have been performed using the SUPERSOMITE facility to investigate the initiation and growth of fatigue cracks at the tips of sharp surface notches subjected to random thermally-induced stress. The experimental situation is complex involving plasticity, random amplitude loading and heat transfer medium/surface coupling. Crack initiation and growth prediction have been considered using the Creager and Neuber methods to compute the strain ranges in the vicinity of the notch root. Good agreement has been obtained between the experimental results and theoretical predictions. The paper reports the results of the analysis of the notch behavior

  5. The role of uric acid in the pathogenesis of diabetic retinopathy based on notch pathway.

    Zhu, Dan-Dan; Wang, Yun-Zhi; Zou, Chen; She, Xin-Ping; Zheng, Zhi

    2018-06-19

    Uric acid has been proposed as an independent risk factor of diabetic retinopathy. Although Notch signaling was reported to be affected in the presence of high concentrations of uric acid or glucose, the underlying mechanisms of hyperuricemia through the Notch signaling pathway to promote the development of diabetic retinopathy remain unknown. We incubated human retinal endothelial cells (HRECs) with high glucose, high uric acid and high glucose plus high glucose respectively and evaluated the apoptosis rate in different treated cells by Tunel staining. We induced diabetic model by intraperitoneally streptozotocin. Then healthy rats and diabetic rats were given with adenine and oteracil potassium by gavage. Using automatic biochemical analyzer to detect blood glucose, uric acid, urea nitrogen, creatinine levels, to verify the success of modeling. The expression and mRNA levels of ICAM-1, IL-6, MCP-1, TNF-a, receptors Notch 1, ligands Dll 1, Dll 4, Jagged 1, Jagged 2 were detected by RT-PCR and Western-Blot. Notch1 siRNA was used to interfere Notch signaling pathway, the expression and mRNA levels of ICAM-1, IL-6, MCP-1 and TNF-α was detected by RT-PCR and Western blot respectively. In vitro models, the apoptosis of HRECs cells in high uric acid plus high glucose group was the most significant. In vitro and vivo models, detection of inflammatory cytokines revealed that the expression of inflammatory cytokines increased most significantly in high uric acid plus high glucose group. Notch signaling pathway activity was also increased most significantly in high uric acid plus high glucose group. After Notch 1 siRNA transfection in high glucose and high glucose plus uric acid group, the activity of Notch signaling pathway was successfully down-regulated. We found that the apoptosis of HRECs was significantly decreased in cells transfected with Notch 1 siRNA compared to the blank vector group, and the expression of inflammatory cytokines in cells was also significantly

  6. Three-dimensional vibrations of cylindrical elastic solids with V-notches and sharp radial cracks

    McGee, O. G.; Kim, J. W.

    2010-02-01

    This paper provides free vibration data for cylindrical elastic solids, specifically thick circular plates and cylinders with V-notches and sharp radial cracks, for which no extensive previously published database is known to exist. Bending moment and shear force singularities are known to exist at the sharp reentrant corner of a thick V-notched plate under transverse vibratory motion, and three-dimensional (3-D) normal and transverse shear stresses are known to exist at the sharp reentrant terminus edge of a V-notched cylindrical elastic solid under 3-D free vibration. A theoretical analysis is done in this work utilizing a variational Ritz procedure including these essential singularity effects. The procedure incorporates a complete set of admissible algebraic-trigonometric polynomials in conjunction with an admissible set of " edge functions" that explicitly model the 3-D stress singularities which exist along a reentrant terminus edge (i.e., α>180°) of the V-notch. The first set of polynomials guarantees convergence to exact frequencies, as sufficient terms are retained. The second set of edge functions—in addition to representing the corner stress singularities—substantially accelerates the convergence of frequency solutions. This is demonstrated through extensive convergence studies that have been carried out by the investigators. Numerical analysis has been carried out and the results have been given for cylindrical elastic solids with various V-notch angles and depths. The relative depth of the V-notch is defined as (1- c/ a), and the notch angle is defined as (360°- α). For a very small notch angle (1° or less), the notch may be regarded as a "sharp radial crack." Accurate (four significant figure) frequencies are presented for a wide spectrum of notch angles (360°- α), depths (1- c/ a), and thickness ratios ( a/ h for plates and h/ a for cylinders). An extended database of frequencies for completely free thick sectorial, semi-circular, and

  7. Ehrlichia chaffeensis TRP120 Activates Canonical Notch Signaling To Downregulate TLR2/4 Expression and Promote Intracellular Survival

    Taslima T. Lina

    2016-07-01

    Full Text Available Ehrlichia chaffeensis preferentially targets mononuclear phagocytes and survives through a strategy of subverting innate immune defenses, but the mechanisms are unknown. We have shown E. chaffeensis type 1 secreted tandem repeat protein (TRP effectors are involved in diverse molecular pathogen-host interactions, such as the TRP120 interaction with the Notch receptor-cleaving metalloprotease ADAM17. In the present study, we demonstrate E. chaffeensis, via the TRP120 effector, activates the canonical Notch signaling pathway to promote intracellular survival. We found that nuclear translocation of the transcriptionally active Notch intracellular domain (NICD occurs in response to E. chaffeensis or recombinant TRP120, resulting in upregulation of Notch signaling pathway components and target genes notch1, adam17, hes, and hey. Significant differences in canonical Notch signaling gene expression levels (>40% were observed during early and late stages of infection, indicating activation of the Notch pathway. We linked Notch pathway activation specifically to the TRP120 effector, which directly interacts with the Notch metalloprotease ADAM17. Using pharmacological inhibitors and small interfering RNAs (siRNAs against γ-secretase enzyme, Notch transcription factor complex, Notch1, and ADAM17, we demonstrated that Notch signaling is required for ehrlichial survival. We studied the downstream effects and found that E. chaffeensis TRP120-mediated activation of the Notch pathway causes inhibition of the extracellular signal-regulated kinase 1/2 (ERK1/2 and p38 mitogen-activated protein kinase (MAPK pathways required for PU.1 and subsequent Toll-like receptor 2/4 (TLR2/4 expression. This investigation reveals a novel mechanism whereby E. chaffeensis exploits the Notch pathway to evade the host innate immune response for intracellular survival.

  8. Fracturing of revision of a cobalt-chrome femoral head after fracturing of a ceramic femoral head, with diffuse metallosis. Case report

    Pedro Miguel Dantas Costa Marques

    2013-04-01

    Full Text Available We presente a case of a fracture of a cobalt-chrome femoral head after revision of a hip total prosthesis with ceramic femoral head fracture. During surgery we found the cobalt-chrome femoral head fracture, wear of the polyethylene and massive metallosis in muscular and cartilaginous tissue. Both femoral stem and acetabular cup were stable and without apparent wearing. After surgical debridement, we promoted the substitution of the femoral head and the acetabular polyethylene by similar ones. After 12 months of follow-up, the patient has no pain complaints, function limit or systemic signs associated with malign metallosis

  9. Femoral shaft bowing in the coronal plane has more significant effect on the coronal alignment of TKA than proximal or distal variations of femoral shape.

    Kim, Jong-Min; Hong, Soo-Heon; Kim, Jong-Min; Lee, Bum-Sik; Kim, Dong-Eun; Kim, Kyung-Ah; Bin, Seong-Il

    2015-07-01

    The aim of this study was to determine (1) variations in the shape of the proximal, middle, and distal femur in a series of Korean patients who had undergone total knee arthroplasty (TKA), (2) the preoperative relationship between these three parameters and the distal valgus cutting angle referenced off the femoral intramedullary guide, and (3) whether there was any relationship between femoral bowing and variations in the shape of the proximal or distal femur in the coronal plane. The preoperative long-standing anteroposterior radiographs of 316 consecutive osteoarthritis patients who underwent primary TKA from 2009 to 2011 were examined. The femoral neck shaft angle, the femoral shaft bowing angle, and the mechanical lateral distal femoral angle were measured to assess the shape of the proximal, middle, and distal femur, respectively. The valgus cutting angle of the femur was defined as the angle between the distal anatomical and mechanical axes of the femur. The study population showed large variations in femoral shape. The mean femoral intramedullary guide angle was 6.5° ± 1.3° (range: 4°-13°). The femoral shaft bowing angle was the factor that showed the strongest correlation with this angle (P shaft angle showed no correlation (n.s.). The femoral shaft bowing angle showed a weak correlation with the mechanical lateral distal femoral angle (P = 0.001), but was not significantly correlated with the femoral neck shaft angle (n.s.). Apparent femoral bowing (>3° of lateral or medial bowing) was found in 42 (13.3 %) of cases (37 cases of lateral bowing and five of medial bowing). Cases with lateral apparent femoral bowing >3° had a distal cutting angle of 8.6° ± 2.2° relative to the femoral intramedullary guide. The femoral intramedullary guide angle was mainly influenced by femoral shaft bowing among femoral deformities in the coronal plane. Therefore, to increase the accuracy of distal femoral cut during TKA, it is necessary to confirm femoral

  10. A biomechanical comparison of proximal femoral nails and locking proximal anatomic femoral plates in femoral fracture fixation A study on synthetic bones

    Korhan Ozkan

    2015-01-01

    Conclusion: The proximal femoral intramedullary nail provides more stability and allows for earlier weight bearing than the locking plate when used for the treatment of unstable intertrochanteric fractures of the femur. Clinicians should be cautious for early weight bearing with locking plate for unstable intertrochanteric femur fractures.

  11. Morphometric analysis of rat femoral vessels under a video magnification system

    Rui Sergio Monteiro de Barros

    Full Text Available Abstract The right femoral vessels of 80 rats were identified and dissected. External lengths and diameters of femoral arteries and femoral veins were measured using either a microscope or a video magnification system. Findings were correlated to animals’ weights. Mean length was 14.33 mm for both femoral arteries and femoral veins, mean diameter of arteries was 0.65 mm and diameter of veins was 0.81 mm. In our sample, rats’ body weights were only correlated with the diameter of their femoral veins.

  12. Trochanteric entry femoral nails yield better femoral version and lower revision rates-A large cohort multivariate regression analysis.

    Yoon, Richard S; Gage, Mark J; Galos, David K; Donegan, Derek J; Liporace, Frank A

    2017-06-01

    Intramedullary nailing (IMN) has become the standard of care for the treatment of most femoral shaft fractures. Different IMN options include trochanteric and piriformis entry as well as retrograde nails, which may result in varying degrees of femoral rotation. The objective of this study was to analyze postoperative femoral version between three types of nails and to delineate any significant differences in femoral version (DFV) and revision rates. Over a 10-year period, 417 patients underwent IMN of a diaphyseal femur fracture (AO/OTA 32A-C). Of these patients, 316 met inclusion criteria and obtained postoperative computed tomography (CT) scanograms to calculate femoral version and were thus included in the study. In this study, our main outcome measure was the difference in femoral version (DFV) between the uninjured limb and the injured limb. The effect of the following variables on DFV and revision rates were determined via univariate, multivariate, and ordinal regression analyses: gender, age, BMI, ethnicity, mechanism of injury, operative side, open fracture, and table type/position. Statistical significance was set at pregression analysis revealed that a lower BMI was significantly associated with a lower DFV (p=0.006). Controlling for possible covariables, multivariate analysis yielded a significantly lower DFV for trochanteric entry nails than piriformis or retrograde nails (7.9±6.10 vs. 9.5±7.4 vs. 9.4±7.8°, pregression analysis. However, this is not to state that the other nail types exhibited abnormal DFV. Translation to the clinical impact of a few degrees of DFV is also unknown. Future studies to more in-depth study the intricacies of femoral version may lead to improved technology in addition to potentially improved clinical outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Case report: AVN of the femoral head five year follow-up of the combination of ipsilateral femoral neck and sub-trochanteric fracture.

    Zhang, Wei; Zhu, Feng; Dong, Hanqing; Xu, Yaozeng

    2016-04-01

    To our knowledge, the type of combination of ipsilateral femoral neck and sub-trochanteric fracture is rare. And the long term follow-up is seldom been reported. A 60 year old woman suffered from a traffic accident. We gave her the intramedullary nail treatment for the combination of ipsilateral femoral neck and sub-trochanteric fracture, and the fracture indeed cured after one year and there is no clue of necrosis of the femoral head, but after 5 years, there is an evidence of necrosis of the femoral head. Combination of ipsilateral femoral neck and sub-trochanteric fracture should be kept in mind. Patients with this unusual fracture should be kept under surveillance for longer than might be thought currently to be necessary for there is a possibility of necrosis of the femoral head, even a nondisplaced femoral neck fracture.

  14. Femoral neck radiography: effect of flexion on visualization

    Garry, S.C.; Jhangri, G.S.; Lambert, R.G.W.

    2005-01-01

    To determine whether flexion improves radiographic visualization of the femoral neck when the femur is externally rotated. Five human femora, with varying neck-shaft and anteversion angles, were measured and immobilized. Degree of flexion required to bring the femoral neck horizontal was measured, varying the rotation. Next, one bone was radiographed in 16 positions, varying rotation in 15 o and flexion in 10 o increments. Radiographs were presented in randomized blinded fashion to 15 staff radiologists for scoring of femoral neck visualization. Following this, all 5 bones were radiographed in 4 positions of rotation and at 0 o and 20 o flexion, and blinded randomized review of radiographs was repeated. Comparisons between angles and rotations were made using the Mann-Whitney test. The flexion angle required to bring the long axis of the femoral neck horizontal correlated directly with the degree of external rotation (ρ o internal rotation to 30 o external rotation (ρ o flexion was applied to bones in external rotation, visualization significantly improved at 15 o (ρ o (ρ o ) of flexion can significantly improve radiographic visualization. This manoeuvre could be useful for radiography of the femoral neck when initial radiographs are inadequate because of external rotation of the leg. (author)

  15. Avascular necrosis of the femoral head in HIV infected patients

    Marcos Almeida Matos

    Full Text Available Avascular necrosis (AVN of the femoral head is an emerging complication in HIV infected patients. It has been suggested that the increased incidence of AVN in this population may be caused by an increased prevalence of predisposing factors for osteonecrosis, including protease inhibitors, hyperlipidemia, corticosteroid use, alcohol and intravenous drug abuse. The aim of this study was to assess the risk factors for avascular necrosis developing in the femoral head of HIV infected individuals. This study consisted of meta-analysis of the secondary data extracted from current literature. The selected articles allowed two study groups to be drawn up for comparison. Group 1 comprised 324 individuals infected by the HIV virus, who did not present femoral head AVN. Group 2 comprised 32 HIV positive patients, who presented femoral head AVN. The parameters used for analysis were as follows: age, gender, sexual preference, use of intravenous drugs, time of diagnosis, CD4+ cell count, use of antiretroviral agents and duration, serum cholesterol and serum triglycerides. The present study found a statistically significant association between hypertriglyceridemia, hypercholesterolemia, sexual preference and intravenous drug abuse. The authors concluded that femoral head osteonecrosis is associated with hyperlipidemia (hypercholesterolemia and hypertriglyceridemia and intravenous drug abuse. This study supports the hypothesis that protease inhibitors play a role in the development of osteonecrosis through a tendency to cause hyperlipidemia.

  16. Valgus Slipped Capital Femoral Epiphysis in Patient with Hypopituitarism

    Yoshihiro Kotoura

    2017-01-01

    Full Text Available Slipped capital femoral epiphysis (SCFE is a common disease of adolescent and the epiphysis is positioned more posteromedially in relation to the femoral neck shaft with varus SCFE; however, posterolateral displacement of the capital epiphysis, valgus SCFE, occurs less frequently. We report a case of valgus SCFE in a 17-year-old boy with hypopituitarism. After falling down, he experienced difficulty in walking. The radiographs were inconclusive; however three-dimensional computed tomography images showed lateral displacement of the epiphysis on the right femoral head. Valgus SCFE was diagnosed. The patient underwent in situ pinning of both sides. In situ pinning on the left side was performed as a prophylactic pinning because of endocrine abnormalities. At the 1-year follow-up, he could walk without any difficulty and there were no signs of pain. The epiphysis is commonly positioned more posteromedially in relation to the femoral neck shaft with most SCFE, but, in this case, the epiphysis slipped laterally. Differential diagnosis included femoral neck fracture (Delbet-Colonna type 1; however, this was less likely due to the absence of other clinical signs. Therefore, we diagnosed the patient as SCFE. When children complain of leg pain and limp, valgus SCFE that may not be visualized on anteroposterior radiographs needs to be considered.

  17. O-Fucose Monosaccharide of Drosophila Notch Has a Temperature-sensitive Function and Cooperates with O-Glucose Glycan in Notch Transport and Notch Signaling Activation*

    Ishio, Akira; Sasamura, Takeshi; Ayukawa, Tomonori; Kuroda, Junpei; Ishikawa, Hiroyuki O.; Aoyama, Naoki; Matsumoto, Kenjiroo; Gushiken, Takuma; Okajima, Tetsuya; Yamakawa, Tomoko; Matsuno, Kenji

    2015-01-01

    Notch (N) is a transmembrane receptor that mediates the cell-cell interactions necessary for many cell fate decisions. N has many epidermal growth factor-like repeats that are O-fucosylated by the protein O-fucosyltransferase 1 (O-Fut1), and the O-fut1 gene is essential for N signaling. However, the role of the monosaccharide O-fucose on N is unclear, because O-Fut1 also appears to have O-fucosyltransferase activity-independent functions, including as an N-specific chaperon. Such an enzymatic activity-independent function could account for the essential role of O-fut1 in N signaling. To evaluate the role of the monosaccharide O-fucose modification in N signaling, here we generated a knock-in mutant of O-fut1 (O-fut1R245A knock-in), which expresses a mutant protein that lacks O-fucosyltransferase activity but maintains the N-specific chaperon activity. Using O-fut1R245A knock-in and other gene mutations that abolish the O-fucosylation of N, we found that the monosaccharide O-fucose modification of N has a temperature-sensitive function that is essential for N signaling. The O-fucose monosaccharide and O-glucose glycan modification, catalyzed by Rumi, function redundantly in the activation of N signaling. We also showed that the redundant function of these two modifications is responsible for the presence of N at the cell surface. Our findings elucidate how different forms of glycosylation on a protein can influence the protein's functions. PMID:25378397

  18. Clinical use of femoral artery hemostasis sticking after interventional procedure via femoral artery access

    Zhu Zhongsheng; Chen Shaoliang; Ye Fei; Zhang Junjie; Zhou Jie; Tian Nailiang; Lin Song; Liu Zhizhong; Xiao Pingxi; Qu Hong

    2010-01-01

    Objective: To observe the clinical effect of the use of femoral artery hemostasis sticking V+PAD after the interventional procedure via femoral artery access. Methods: By using random permutation list 80 patients, who decided to receive coronary angiography and percutaneous transluminal coronary angioplasty, were randomly selected. Of the 80 patients, hemostasis sticking V + PAD was employed in 40 patients with even numbers (trial group), only manual compression was adopted to stop bleeding in another 40 patients with odd numbers (control group). All the patients were informed about this trial and had to sign a consent letter. The pressure time, the treatment method of access site after hemostasis, the posture in bed, the immobilization time, the comfort degree of patients, the complications of access site prior to discharge, etc. were observed and the results were compared between two groups. Results: There was no significant difference between two groups as respect to age, gender ratios,activated clotting time (ACT) value and blood pressure. However, significantly difference in the compression time and bed rest time existed between the two groups. The compression time in trial group and control group was (7.9 ± 0.5) min and (19.8 ± 5.1) min respectively (P<0.01), while the bed rest time in trial group and control group was (6.1 ± 5.0) hours and (23.9 ± 0.2) hours respectively (P<0.01). All patients in trial group was supine in bed with the head side of the bed raised at 30 degree immediately after the procedure, and the head side of the bed was further raised to 90 degree one hour later. The puncture site was bandaged with conventional compression and immobilization was not employed. Patients could lie in bed with free posture and the patient's comfort degree was greatly improved. During hospitalization no complications related to puncture site occurred in all patients except one obese woman in trial group who developed pseudoaneurysm. Conclusion: Femoral

  19. Tensile behavior of unnotched and notched tungsten--copper laminar composites

    Hoffman, C.A.

    1976-06-01

    Relations were studied between the tensile strengths of unnotched and of notched, and elastic moduli of unnotched laminar sheet or foil composites and the amounts of reinforcement. Tungsten was used as the reinforcement and copper as the matrix, and the tests were run at room temperature. Three thicknesses of tungsten (i.e., 0.00254, 0.0127, and 0.0254 cm (0.001, 0.005, and 0.010 in) were used, and the nominal volume fraction of tungsten was varied from about 0.05 to 0.95. It was found that the tensile strength of the unnotched specimens could be related to the amount of reinforcement, as could the elastic moduli, and that these values could be predicted by use of the rule of mixtures. The tensile strengths of the notched laminar composites could be predicted by use of the rule of mixtures using strengths for notched constituents, provided notch effects did not predominate. (Author)

  20. Genetic deletion of Rnd3 in neural stem cells promotes proliferation via upregulation of Notch signaling.

    Dong, Huimin; Lin, Xi; Li, Yuntao; Hu, Ronghua; Xu, Yang; Guo, Xiaojie; La, Qiong; Wang, Shun; Fang, Congcong; Guo, Junli; Li, Qi; Mao, Shanping; Liu, Baohui

    2017-10-31

    Rnd3, a Rho GTPase, is involved in the inhibition of actin cytoskeleton dynamics through the Rho kinase-dependent signaling pathway. We previously demonstrated that mice with genetic deletion of Rnd3 developed a markedly larger brain compared with wild-type mice. Here, we demonstrate that Rnd3 knockout mice developed an enlarged subventricular zone, and we identify a novel role for Rnd3 as an inhibitor of Notch signaling in neural stem cells. Rnd3 deficiency, both in vivo and in vitro , resulted in increased levels of Notch intracellular domain protein. This led to enhanced Notch signaling and promotion of aberrant neural stem cell growth, thereby resulting in a larger subventricular zone and a markedly larger brain. Inhibition of Notch activity abrogated this aberrant neural stem cell growth.

  1. Role of CSL-dependent and independent Notch signaling pathways in cell apoptosis.

    Zeng, Chong; Xing, Rui; Liu, Jing; Xing, Feiyue

    2016-01-01

    Apoptosis is a normally biological phenomenon in various organisms, involving complexly molecular mechanisms with a series of signaling processes. Notch signaling is found evolutionarily conserved in many species, playing a critical role in embryonic development, normal tissue homeostasis, angiogenesis and immunoregulation. The focus of this review is on currently novel advances about roles of CSL-dependent and independent Notch signaling pathways in cell apoptosis. The CSL can bind Notch intracellular domain (NIC) to act as a switch in mediating transcriptional activation or inactivation of the Notch signaling pathway downstream genes in the nucleus. It shows that CSL-dependent signaling regulates the cell apoptosis through Hes-1-PTEN-AKT-mTOR signaling, but rather the CSL-independent signaling mediates the cell apoptosis possibly via NIC-mTORC2-AKT-mTOR signaling, providing a new insight into apoptotic mechanisms.

  2. A U-Shaped Slot UWB Antenna with Flexible and Wide Tunable Dual Notch Band

    Zhang Zhongmin

    2016-01-01

    Full Text Available A coplanar waveguide (CPW fed ultra-wideband (UWB antenna with flexible and wide tunable dual bandnotched characteristics is proposed in this paper. The dual band-notched function is achieved by using an U-shaped slot inserted into the ellipse radiation patch and by using an elliptic parasitic slit placed near the ground plane. The wide tunable band-notched characteristic is implemented by adjusting the length of U-shaped slot and by adjusting the length of ellipse parasitic slit. The design aims to achieve wide reconfigurable band-notched features on the UWB antenna. The simulated results indicate that the proposed antenna has a wide bandwidth (VSWR under 2 from 2.9GHz to 12.6GHz with fractional bandwidth of 125%, and has a wide tunable notch band center frequency from 4.5GHz to 12.4GHz.

  3. Impaired embryonic haematopoiesis yet normal arterial development in the absence of the Notch ligand Jagged1

    Robert-Moreno, Àlex; Robert-Moreno, Àlex; Guiu, Jordi

    2008-01-01

    Specific deletion of Notch1 and RBPjκ in the mouse results in abrogation of definitive haematopoiesis concomitant with the loss of arterial identity at embryonic stage. As prior arterial determination is likely to be required for the generation of embryonic haematopoiesis, it is difficult...... to establish the specific haematopoietic role of Notch in these mutants. By analysing different Notch-ligand-null embryos, we now show that Jagged1 is not required for the establishment of the arterial fate but it is required for the correct execution of the definitive haematopoietic programme, including...... activation of Notch1 is responsible for regulating GATA2 expression in the AGM, which in turn is essential for definitive haematopoiesis in the mouse....

  4. Power Line Interference Removal from Electrocardiogram Using a Simplified Lattice Based Adaptive IIR Notch Filter

    Dhillon, Santpal

    2001-01-01

    ...) notch filter with a simplified adaptation algorithm for removal of power line frequency from ECG signals, The performance of this filter is better as compared to a second order infinite impulse response (IIR...

  5. Spoof surface plasmon polaritons based notch filter for ultra-wideband microwave waveguide

    Xiao, Binggang; Li, Sheng-Hua; Xiao, Sanshui

    2016-01-01

    Spoof surface plasmon polaritons based notch filter for ultra-wideband microwave waveguide is proposed. Owing to subwavelength confinement, such a filter has advantage in the structure size without sacrificing the performance. The spoof SPP based notch is introduced to suppress the WLAN and satel...... and satellite communication signals. Due to planar structures proposed here, it is easy to integrate in the microwave integrated systems, which can play an important role in the microwave communication circuit and system.......Spoof surface plasmon polaritons based notch filter for ultra-wideband microwave waveguide is proposed. Owing to subwavelength confinement, such a filter has advantage in the structure size without sacrificing the performance. The spoof SPP based notch is introduced to suppress the WLAN...

  6. Notch2 transduction by feline leukemia virus in a naturally infected cat.

    Watanabe, Shinya; Ito, Jumpei; Baba, Takuya; Hiratsuka, Takahiro; Kuse, Kyohei; Ochi, Haruyo; Anai, Yukari; Hisasue, Masaharu; Tsujimoto, Hajime; Nishigaki, Kazuo

    2014-04-01

    Feline leukemia virus (FeLV) induces neoplastic and nonneoplastic diseases in cats. The transduction of cellular genes by FeLV is sometimes observed and associated with neoplastic diseases including lymphoma and sarcoma. Here, we report the first natural case of feline Notch2 transduction by FeLV in an infected cat with multicentric lymphoma and hypercalcemia. We cloned recombinant FeLVs harboring Notch2 in the env gene. Notch2 was able to activate expression of a reporter gene, similar to what was previously reported in cats with experimental FeLV-induced thymic lymphoma. Our findings suggest that the transduction of Notch2 strongly correlates with FeLV-induced lymphoma.

  7. Digital data for the Hazens Notch and a portion of the Lowell quadrangles, Vermont

    Vermont Center for Geographic Information — Digital Data from VG03-3B Digital data for the Hazens Notch and a portion of the Lowell quadrangles, Vermont: Vermont Geological Survey Open File Report VG03-3B, The...

  8. Microbiota promote secretory cell determination in the intestinal epithelium by modulating host Notch signaling.

    Troll, Joshua V; Hamilton, M Kristina; Abel, Melissa L; Ganz, Julia; Bates, Jennifer M; Stephens, W Zac; Melancon, Ellie; van der Vaart, Michiel; Meijer, Annemarie H; Distel, Martin; Eisen, Judith S; Guillemin, Karen

    2018-02-23

    Resident microbes promote many aspects of host development, although the mechanisms by which microbiota influence host tissues remain unclear. We showed previously that the microbiota is required for allocation of appropriate numbers of secretory cells in the zebrafish intestinal epithelium. Because Notch signaling is crucial for secretory fate determination, we conducted epistasis experiments to establish whether the microbiota modulates host Notch signaling. We also investigated whether innate immune signaling transduces microbiota cues via the Myd88 adaptor protein. We provide the first evidence that microbiota-induced, Myd88-dependent signaling inhibits host Notch signaling in the intestinal epithelium, thereby promoting secretory cell fate determination. These results connect microbiota activity via innate immune signaling to the Notch pathway, which also plays crucial roles in intestinal homeostasis throughout life and when impaired can result in chronic inflammation and cancer. © 2018. Published by The Company of Biologists Ltd.

  9. Targeting Homologous Recombination in Notch-Driven C. elegans Stem Cell and Human Tumors.

    Xinzhu Deng

    Full Text Available Mammalian NOTCH1-4 receptors are all associated with human malignancy, although exact roles remain enigmatic. Here we employ glp-1(ar202, a temperature-sensitive gain-of-function C. elegans NOTCH mutant, to delineate NOTCH-driven tumor responses to radiotherapy. At ≤20°C, glp-1(ar202 is wild-type, whereas at 25°C it forms a germline stem cell⁄progenitor cell tumor reminiscent of human cancer. We identify a NOTCH tumor phenotype in which all tumor cells traffic rapidly to G2⁄M post-irradiation, attempt to repair DNA strand breaks exclusively via homology-driven repair, and when this fails die by mitotic death. Homology-driven repair inactivation is dramatically radiosensitizing. We show that these concepts translate directly to human cancer models.

  10. Notched Strength of Woven Fabric Kenaf Composite Plates with Different Stacking Sequences and Hole Sizes

    Hans Romayne Anders

    2016-01-01

    Full Text Available Advantages of using kenaf fibres over synthetic fibres in composites manufacturing are relatively cheap, less abrasive and hazardous during handling, and renewable materials. Current work investigates parametric effects on notched strength of woven fabric kenaf polymer composites plates with variation of lay-up types, notch sizes and plate thickness. Testing coupons are prepared using hand lay-up technique and circular notch were drilled prior to mechanical testing. Stress concentration at the notch edge promotes micro-damage event as tensile loading was applied leading to crack initiation and propagations across the plate width. It is suggested that woven fabric kenaf polymer composites are potentially used in low and medium load bearing applications.

  11. Roles of Notch1 Signaling in Regulating Satellite Cell Fates Choices and Postnatal Skeletal Myogenesis.

    Shan, Tizhong; Xu, Ziye; Wu, Weiche; Liu, Jiaqi; Wang, Yizhen

    2017-11-01

    Adult skeletal muscle stem cells, also called satellite cells, are indispensable for the growth, maintenance, and regeneration of the postnatal skeletal muscle. Satellite cells, predominantly quiescent in mature resting muscles, are activated after skeletal muscle injury or degeneration. Notch1 signaling is an evolutionarily conserved pathway that plays crucial roles in satellite cells homeostasis and postnatal skeletal myogenesis and regeneration. Activation of Notch1 signaling promotes the muscle satellite cells quiescence and proliferation, but inhibits differentiation of muscle satellite cells. Notably, the new roles of Notch1 signaling during late-stage of skeletal myogenesis including in post-differentiation myocytes and post-fusion myotubes have been recently reported. Here, we mainly review and discuss the regulatory roles of Notch1 in regulating satellite cell fates choices and skeletal myogenesis. J. Cell. Physiol. 232: 2964-2967, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. A STUDY OF UNSTABLE INTERTROCHANTERIC FEMORAL FRACTURES TREATED BY TROCHANTERIC FEMORAL NAIL

    Sreenivasa Neikar

    2017-11-01

    Full Text Available BACKGROUND Intertrochanteric fracture is one of the most common fracture of the hip especially in the elderly. The incidence of intertrochanteric fracture is rising because of the increase in number of elderly population along with superadded osteoporosis. MATERIALS AND METHODS Study included cases of unstable intertrochanteric fractures (AO and OTA Classification 31-A2 and 31-A3 fracture patterns that were operated with the short trochanteric femoral nail, which fitted into the inclusion criteria done in medical college hospital, Vijayanagara Institute of Medical Sciences, Bellary, from February 2015 to September 2016. RESULTS The age distribution was from 40 to 80 years. The largest group of patients were from 61 to 70 years. The average age was 60.5 years. The number of male patients in our series was 20 (66.7% and female was 10 (33.3%. Right side was affected in 11 cases (36.7% and left side in 19 cases (63.3%. Good reduction was achieved in 23 patients (76.7%. Acceptable reduction was achieved in 7 (23.3% patients due to severe comminution. In our study, 25 patients (83.33% had no complications. We encountered one intraoperative complication in the form of greater trochanter splintering, while inserting the nail. In our study, we encountered following postoperative complications. We noticed one case of delayed union, one case of Z effect and 2 cases of varus malunion. CONCLUSION We conclude that short trochanteric femoral nail provides good fixation for unstable intertrochanteric fractures if proper preoperative planning, good reduction and surgical technique are followed leading to high rate of bone union and minimal soft tissue damage especially for Asian patients with relatively small femora.

  13. A Case of Late Femoral Pseudoaneurysm Caused by Stent Disconnection

    Rivolta, Nicola; Fontana, Federico; Piffaretti, Gabriele; Tozzi, Matteo; Carrafiello, Gianpaolo

    2010-01-01

    We present the case of a late superficial femoral artery stent disconnection causing an asymptomatic pseudoaneurysm successfully treated with a stent-graft. A 67-year-old female was referred to our department for evaluation of claudication of the left lower limb and was diagnosed to have a total occlusion of the superficial femoral artery. Three nitinol stents were used to revascularize this artery. At 48 months, duplex-ultrasonography control revealed the presence of a 45-mm saccular femoral dilatation; X-rays and CT angiography showed fractures of the proximal stents and the presence of a pseudoaneurysm at the site of the distal stents disconnection. The pseudoaneurysm was excluded using two stent-grafts. We conclude that patients and surgeons should be aware of structural complications with all stents. Rigorous follow-up controls should be mandatory. Endovascular repair proved to be feasible and durable to manage a previous endovascular procedure.

  14. Femoral arteriographic finding in acute ergotism: Report of A Case

    Rhee, H S; Lee, K N; Cha, S B [St. Mary' s Hospital, Catholic Medical College, Seoul (Korea, Republic of)

    1971-10-15

    A case of acute ergotism with angiographic demonstration of bilateral femoral artery involvement is reported. A 27-year-old married woman was admitted because of sudden onset of severe pain in both flanks and lower legs, followed by numbness and coldness of the skin on both legs. The attack occurred after the administration of ergot tartrate as postpartum care. Femoral arteriography was performed on 10th day of illness with the Seldinger technic. The femoral arteries were generally smaller in caliber than normal. There was no definite evidence of occlusive disease. Findings were more or less symmetrical and extended to lower legs where only fine branches were visualized. The final diagnosis was diffuse vasospasm due to acute ergotism with secondary occlusion of the arteries of lower leg bilaterally.

  15. Emergency Stenting of a Ruptured Infected Anastomotic Femoral Pseudoaneurysm

    Klonaris, Chris; Katsargyris, Athanasios; Matthaiou, Alexandros; Giannopoulos, Athanasios; Tsigris, Chris; Papadopouli, Katerina; Tsiodras, Sotiris; Bastounis, Elias

    2007-01-01

    A 74-year-old man presented with a ruptured infected anastomotic femoral pseudoaneurysm. Due to severe medical comorbidities he was considered unsuitable for conventional surgical management and underwent an emergency endovascular repair with a balloon-expandable covered stent. The pseudoaneurysm was excluded successfully and the patient had an uneventful postoperative recovery with long-term suppressive antimicrobials. He remained well for 10 months after the procedure with no signs of recurrent local or systemic infection and finally died from an acute myocardial infarction. To our knowledge, emergency endovascular treatment of a free ruptured bleeding femoral artery pseudoaneurysm has not been documented before in the English literature. This case illustrates that endovascular therapy may be a safe and efficient alternative in the emergent management of ruptured infected anastomotic femoral artery pseudoaneurysms when traditional open surgery is contraindicated

  16. Femoral arteriographic finding in acute ergotism: Report of A Case

    Rhee, H. S.; Lee, K. N.; Cha, S. B.

    1971-01-01

    A case of acute ergotism with angiographic demonstration of bilateral femoral artery involvement is reported. A 27-year-old married woman was admitted because of sudden onset of severe pain in both flanks and lower legs, followed by numbness and coldness of the skin on both legs. The attack occurred after the administration of ergot tartrate as postpartum care. Femoral arteriography was performed on 10th day of illness with the Seldinger technic. The femoral arteries were generally smaller in caliber than normal. There was no definite evidence of occlusive disease. Findings were more or less symmetrical and extended to lower legs where only fine branches were visualized. The final diagnosis was diffuse vasospasm due to acute ergotism with secondary occlusion of the arteries of lower leg bilaterally

  17. Avascular Necrosis of the Femoral Head: Are Any Genes Involved?

    Pouya, Farzaneh; Kerachian, Mohammad Amin

    2015-01-01

    Avascular necrosis of the femoral head (ANFH) is a pathologic process that results from interruption of blood supply to the femur bone resulting in the death of bone cells and collapse of the femoral head. Nontraumatic ANFH continues to be a significant challenge to orthopedic surgeons. While the exact mechanisms remain elusive, many new insights have emerged from research in the last decade that has given us a clearer picture of the pathogenesis of nontraumatic ANFH. Progression to the end stage of ANFH appears to be related to five main mechanisms: hypercoagulable conditions, angiogenesis suppressions, hyperadipogenesis, heritable states, and switching the bone remodelling into bone resorption. Researchers have been examining the pathogenic mechanisms of ANFH but none of these theories have been firmly confirmed although some appear more plausible than the others. All of these factors can switch bone remodelling into bone resorption, which can further lead to ANFH progression ending up to femoral head collapse. PMID:26213697

  18. Assessment of femoral head perfusion by dynamic MR imaging

    Ochi, Ryuya; Nakano, Tetsuo; Miyazono, Kazuki; Tsurugami, Hiroshi; Fukuda, Tomohiro; Inaba, Daisuke; Takada, Koji

    2004-01-01

    We studied femoral head perfusion in 21 femoral neck fractures using dynamic MR imaging (MRI) between November 2001 and July 2002. MRI patterns divided into four groups when the results between the fractured side and unaffected side were compared. Femoral head perfusion at the fractured side was normal in Type A, about half in Type B, and absent in Type C. When perfusion at both the fractured side and unaffected side was absent, Exceptional Type was suspected. The Garden I group consisted of one Type B. The Garden II group consisted of one Type A, six Type B, one Type C, and two Exceptional Type. The Garden III group consisted of two Type B and one Type C, and the Garden IV group consisted of six Type C and one Exceptional Type. Post operations of by internal fixation confirmed the incidence of aseptic necrosis using MRI. (author)

  19. A cementless, proximally fixed anatomic femoral stem induces high micromotion with nontraumatic femoral avascular necrosis: A finite element study

    Wen-Chuan Chen

    2014-07-01

    Full Text Available Decrease in bone mineral density of metaphysis in patients with nontraumatic avascular necrosis of the femoral head (AVN is considered the main factor leading to aseptic loosening of the femoral component. Researchers have hypothesized that a cementless, anatomic stem fixed proximally to the metaphysis has a higher risk for aseptic loosening than a straight stem that is fixed at the diaphysis in patients with nontraumatic AVN. The purpose of the current study was to evaluate the effects of cancellous bone stiffness at the metaphysis and stem geometry on the micromotion of the femoral stem relative to the femur. The VerSys (straight and ABG (anatomic femoral stems were enrolled in this finite element study to determine the performance of prosthetic micromotion. The simulated load to the hip joint during heel strike was assigned. Results showed that the VerSys model represented better resistance in micromotion between the bone/stem interface than the ABG model in either normal or poor cancellous bone stiffness at the metaphysis. The bone quality at the metaphysis of patients with nontraumatic AVN should be considered prior to selecting a femoral stem. In consideration of initial stability, acementless, straight stem that fits the isthmus is more favourable than an anatomic stem that is fixed to the proximal area of the canal.

  20. A micro-architectural evaluation of osteoporotic human femoral heads to guide implant placement in proximal femoral fractures.

    Jenkins, Paul J; Ramaesh, Rishikesan; Pankaj, Pankaj; Patton, James T; Howie, Colin R; Goffin, Jérôme M; Merwe, Andrew van der; Wallace, Robert J; Porter, Daniel E; Simpson, A Hamish

    2013-10-01

    The micro-architecture of bone has been increasingly recognized as an important determinant of bone strength. Successful operative stabilization of fractures depends on bone strength. We evaluated the osseous micro-architecture and strength of the osteoporotic human femoral head. 6 femoral heads, obtained during arthroplasty surgery for femoral neck fracture, underwent micro-computed tomography (microCT) scanning at 30 μm, and bone volume ratio (BV/TV), trabecular thickness, structural model index, connection density, and degree of anisotropy for volumes of interest throughout the head were derived. A further 15 femoral heads underwent mechanical testing of compressive failure stress of cubes of trabecular bone from different regions of the head. The greatest density and trabecular thickness was found in the central core that extended from the medial calcar to the physeal scar. This region also correlated with the greatest degree of anisotropy and proportion of plate-like trabeculae. In the epiphyseal region, the trabeculae were organized radially from the physeal scar. The weakest area was found at the apex and peripheral areas of the head. The strongest region was at the center of the head. The center of the femoral head contained the strongest trabecular bone, with the thickest, most dense trabeculae. The apical region was weaker. From an anatomical and mechanical point of view, implants that achieve fixation in or below this central core may achieve the most stable fixation during fracture healing.

  1. Opposing actions of endocannabinoids on cholangiocarcinoma growth is via the differential activation of Notch signaling

    Frampton, Gabriel; Coufal, Monique [Department of Internal Medicine, Texas A and M Health Science Center College of Medicine, Temple, TX (United States); Li, Huang [Department of Internal Medicine, Texas A and M Health Science Center College of Medicine, Temple, TX (United States); Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Ramirez, Jonathan [Digestive Disease Research Center, Scott and White Hospital, Temple, TX (United States); DeMorrow, Sharon, E-mail: demorrow@medicine.tamhsc.edu [Department of Internal Medicine, Texas A and M Health Science Center College of Medicine, Temple, TX (United States); Digestive Disease Research Center, Scott and White Hospital, Temple, TX (United States)

    2010-05-15

    The endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG) have opposing effects on cholangiocarcinoma growth. Implicated in cancer, Notch signaling requires the {gamma}-secretase complex for activation. The aims of this study were to determine if the opposing effects of endocannabinoids depend on the differential activation of the Notch receptors and to demonstrate that the differential activation of these receptors are due to presenilin 1 containing- and presenilin 2 containing-{gamma}-secretase complexes. Mz-ChA-1 cells were treated with AEA or 2-AG. Notch receptor expression, activation, and nuclear translocation were determined. Specific roles for Notch 1 and 2 on cannabinoid-induced effects were determined by transient transfection of Notch 1 or 2 shRNA vectors before stimulation with AEA or 2-AG. Expression of presenilin 1 and 2 was determined after AEA or 2-AG treatment, and the involvement of presenilin 1 and 2 in the cannabinoid-induced effects was demonstrated in cell lines with low presenilin 1 or 2 expression. Antiproliferative effects of AEA required increased Notch 1 mRNA, activation, and nuclear translocation, whereas the growth-promoting effects induced by 2-AG required increased Notch 2 mRNA expression, activation, and nuclear translocation. AEA increased presenilin 1 expression and recruitment into the {gamma}-secretase complex, whereas 2-AG increased expression and recruitment of presenilin 2. The development of novel therapeutic strategies aimed at modulating the endocannabinoid system or mimicking the mode of action of AEA on Notch signaling pathways would prove beneficial for cholangiocarcinoma management.

  2. Silybin-mediated inhibition of Notch signaling exerts antitumor activity in human hepatocellular carcinoma cells.

    Song Zhang

    Full Text Available Hepatocellular carcinoma (HCC is a global health burden that is associated with limited treatment options and poor patient prognoses. Silybin (SIL, an antioxidant derived from the milk thistle plant (Silybum marianum, has been reported to exert hepatoprotective and antitumorigenic effects both in vitro and in vivo. While SIL has been shown to have potent antitumor activity against various types of cancer, including HCC, the molecular mechanisms underlying the effects of SIL remain largely unknown. The Notch signaling pathway plays crucial roles in tumorigenesis and immune development. In the present study, we assessed the antitumor activity of SIL in human HCC HepG2 cells in vitro and in vivo and explored the roles of the Notch pathway and of the apoptosis-related signaling pathway on the activity of SIL. SIL treatment resulted in a dose- and time-dependent inhibition of HCC cell viability. Additionally, SIL exhibited strong antitumor activity, as evidenced not only by reductions in tumor cell adhesion, migration, intracellular glutathione (GSH levels and total antioxidant capability (T-AOC but also by increases in the apoptotic index, caspase3 activity, and reactive oxygen species (ROS. Furthermore, SIL treatment decreased the expression of the Notch1 intracellular domain (NICD, RBP-Jκ, and Hes1 proteins, upregulated the apoptosis pathway-related protein Bax, and downregulated Bcl2, survivin, and cyclin D1. Notch1 siRNA (in vitro or DAPT (a known Notch1 inhibitor, in vivo further enhanced the antitumor activity of SIL, and recombinant Jagged1 protein (a known Notch ligand in vitro attenuated the antitumor activity of SIL. Taken together, these data indicate that SIL is a potent inhibitor of HCC cell growth that targets the Notch signaling pathway and suggest that the inhibition of Notch signaling may be a novel therapeutic intervention for HCC.

  3. Notch signaling regulates expression of Mcl-1 and apoptosis in PPD-treated macrophages.

    Palaga, Tanapat; Ratanabunyong, Siriluk; Pattarakankul, Thitiporn; Sangphech, Naunpun; Wongchana, Wipawee; Hadae, Yukihiro; Kueanjinda, Patipark

    2013-09-01

    Macrophages are cellular targets for infection by bacteria and viruses. The fate of infected macrophages plays a key role in determining the outcome of the host immune response. Apoptotic cell death of macrophages is considered to be a protective host defense that eliminates pathogens and infected cells. In this study, we investigated the involvement of Notch signaling in regulating apoptosis in macrophages treated with tuberculin purified protein derivative (PPD). Murine bone marrow-derived macrophages (BMMs) treated with PPD or infected with Mycobacterium bovis Bacillus Calmette-Guérin (BCG) induced upregulation of Notch1. This upregulation correlated well with the upregulation of the anti-apoptotic gene mcl-1 both at the transcriptional and translational levels. Decreased levels of Notch1 and Mcl-1 were observed in BMM treated with PPD when a gamma secretase inhibitor (GSI), which inhibits the processing of Notch receptors, was used. Moreover, silencing Notch1 in the macrophage-like cell line RAW264.7 decreased Mcl-1 protein expression, suggesting that Notch1 is critical for Mcl-1 expression in macrophages. A significant increase in apoptotic cells was observed upon treatment of BMM with PPD in the presence of GSI compared to the vehicle-control treated cells. Finally, analysis of the mcl-1 promoter in humans and mice revealed a conserved potential CSL/RBP-Jκ binding site. The association of Notch1 with the mcl-1 promoter was confirmed by chromatin immunoprecipitation. Taken together, these results indicate that Notch1 inhibits apoptosis of macrophages stimulated with PPD by directly controlling the mcl-1 promoter.

  4. Prognostic value of Notch-1 expression in hepatocellular carcinoma: a meta-analysis

    Wu T

    2015-10-01

    Full Text Available Tao Wu,1 Min Jiao,1 Li Jing,1 Min-Cong Wang,1 Hai-Feng Sun,2 Qing Li,1 Yi-Yang Bai,1 Yong-Chang Wei,1 Ke-Jun Nan,1 Hui Guo1 1Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, 2Department of Oncology, Shaanxi Cancer Hospital, Xi’an, People’s Republic of China Abstract: Association of Notch-1 expression with prognosis of patients with hepatocellular carcinoma (HCC remains controversial. We conducted a meta-analysis to reevaluate the association of Notch-1 expression with clinicopathological characteristics and prognosis of HCC. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure were searched to look for relevant studies. The association between Notch-1 expression and clinicopathological parameters and overall survival (OS was then reassessed using the meta-analysis for odds ratio (OR or hazard ratio (HR and 95% confidence interval (CI. A total of seven studies, including 810 HCC patients, were eligible for the meta-analysis. Our data showed that high Notch-1 expression was able to predict poor OS (HR 1.50, 95% CI 1.17–1.83, P=0.0001. The pooled OR showed that high Notch-1 expression was significantly associated with tumor metastasis (OR 0.37, 95% CI 0.16–0.86, P=0.02 and tumor size >5 cm (OR 0.48, 95% CI 0.26–0.88, P=0.02. In contrast, there was no association between high Notch-1 expression and tumor differentiation, late TNM stage, tumor number, and portal vein invasion of HCC. In conclusion, Notch-1 overexpression might predict poorer survival and more aggressive behavior in patients with HCC. Keywords: hepatocellular carcinoma, Notch-1, prognosis, clinicopathological features, meta-analysis

  5. Estimation of Low Cycle Fatigue Response of 316 LN Stainless Steel in the Presence of Notch

    Agrawal, Richa; Veerababu, J.; Goyal, Sunil; Sandhya, R.; Uddanwadiker, Rashmi; Padole, Pramod

    2018-02-01

    Notches introduced in the plain specimen result in the multiaxial state of stress that exists in the actual components due to the presence of flaws and defects. In the present work, low cycle fatigue life estimation of plain and notched specimens of 316 LN stainless steel is carried out at room temperature and 823 K. The plain and notched specimens with different notch radii were subjected to varying strain amplitudes ranging from ± 0.25 to ± 1.0% at a strain rate of 3 × 10-3 s-1. The fatigue life decreased in the presence of notch for all strain amplitudes at both the temperatures. The decrease in fatigue life was found to be more at room temperature than at 823 K. The fatigue life of the notched specimen decreased by approximately 94.2% compared to plain specimen at room temperature. However, at 823 K the decrease in fatigue life for notched specimen was approximately 84.6%. Low cycle fatigue life of the plain and notched specimens was estimated by Neuber's rule and finite element analysis approach. Neuber's rule overestimated the fatigue life by maximum factor of 2.6 for specimens at room temperature and by maximum factor of 5 for specimens at 823 K. However, it gives closer approximation at higher strain amplitudes at 823 K. Life estimation by finite element analysis at room temperature was within a factor of 1.5 as compared to experimental life, whereas it underestimated the fatigue life within a factor of 6 at high temperature.

  6. Metabolic syndrome impairs notch signaling and promotes apoptosis in chronically ischemic myocardium.

    Elmadhun, Nassrene Y; Sabe, Ashraf A; Lassaletta, Antonio D; Chu, Louis M; Kondra, Katelyn; Sturek, Michael; Sellke, Frank W

    2014-09-01

    Impaired angiogenesis is a known consequence of metabolic syndrome (MetS); however, the mechanism is not fully understood. Recent studies have shown that the notch signaling pathway is an integral component of cardiac angiogenesis. We tested, in a clinically relevant swine model, the effects of MetS on notch and apoptosis signaling in chronically ischemic myocardium. Ossabaw swine were fed either a regular diet (control [CTL], n = 8) or a high-cholesterol diet (MetS, n = 8) to induce MetS. An ameroid constrictor was placed to induce chronic myocardial ischemia. Eleven weeks later, the wine underwent cardiac harvest of the ischemic myocardium. Downregulation of pro-angiogenesis proteins notch2, notch4, jagged2, angiopoietin 1, and endothelial nitric oxide synthase were found in the MetS group compared with the CTL group. Also, upregulation of pro-apoptosis protein caspase 8 and downregulation of anti-angiogenesis protein phosphorylated forkhead box transcription factor 03 and pro-survival proteins phosphorylated P38 and heat shock protein 90 were present in the MetS group. Cell death was increased in the MetS group compared with the CTL group. Both CTL and MetS groups had a similar arteriolar count and capillary density, and notch3 and jagged1 were both similarly concentrated in the smooth muscle wall. MetS in chronic myocardial ischemia significantly impairs notch signaling by downregulating notch receptors, ligands, and pro-angiogenesis proteins. MetS also increases apoptosis signaling, decreases survival signaling, and increases cell death in chronically ischemic myocardium. Although short-term angiogenesis appears unaffected in this model of early MetS, the molecular signals for angiogenesis are impaired, suggesting that inhibition of notch signaling might underlie the decreased angiogenesis in later stages of MetS. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  7. Context-Dependent Functional Divergence of the Notch Ligands DLL1 and DLL4 In Vivo.

    Kristina Preuße

    2015-06-01

    Full Text Available Notch signalling is a fundamental pathway that shapes the developing embryo and sustains adult tissues by direct communication between ligand and receptor molecules on adjacent cells. Among the ligands are two Delta paralogues, DLL1 and DLL4, that are conserved in mammals and share a similar structure and sequence. They activate the Notch receptor partly in overlapping expression domains where they fulfil redundant functions in some processes (e.g. maintenance of the crypt cell progenitor pool. In other processes, however, they appear to act differently (e.g. maintenance of foetal arterial identity raising the questions of how similar DLL1 and DLL4 really are and which mechanism causes the apparent context-dependent divergence. By analysing mice that conditionally overexpress DLL1 or DLL4 from the same genomic locus (Hprt and mice that express DLL4 instead of DLL1 from the endogenous Dll1 locus (Dll1Dll4ki, we found functional differences that are tissue-specific: while DLL1 and DLL4 act redundantly during the maintenance of retinal progenitors, their function varies in the presomitic mesoderm (PSM where somites form in a Notch-dependent process. In the anterior PSM, every cell expresses both Notch receptors and ligands, and DLL1 is the only activator of Notch while DLL4 is not endogenously expressed. Transgenic DLL4 cannot replace DLL1 during somitogenesis and in heterozygous Dll1Dll4ki/+ mice, the Dll1Dll4ki allele causes a dominant segmentation phenotype. Testing several aspects of the complex Notch signalling system in vitro, we found that both ligands have a similar trans-activation potential but that only DLL4 is an efficient cis-inhibitor of Notch signalling, causing a reduced net activation of Notch. These differential cis-inhibitory properties are likely to contribute to the functional divergence of DLL1 and DLL4.

  8. miR-935 suppresses gastric signet ring cell carcinoma tumorigenesis by targeting Notch1 expression

    Yan, Chao [Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730 (China); Yu, Jianchun, E-mail: yu_jchpumch@163.com [Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730 (China); Kang, Weiming [Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730 (China); Liu, Yuqin [Cell Culture Center, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005 (China); Ma, Zhiqiang; Zhou, Li [Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730 (China)

    2016-01-29

    Gastric signet ring cell carcinoma (GSRCC) is a unique pathological type of gastric carcinoma that is extremely invasive and has a poor prognosis. Expression of microRNAs (miRNAs) has been closely linked to the carcinogenesis of gastric cancer and has been considered as a powerful prognostic marker. The function of miR-935 has never been reported in cancer before. We found, using microRNA array, that expression of miR-935 in GSRCC cell lines is lower than in non-GSRCC cell lines, and enhanced expression of miR-935 in GSRCC cell-lines inhibit cell proliferation, migration and invasion. We also identified Notch1 as a direct target of miR-935. Knockdown of Notch1 reduced proliferation, migration/invasion of GSRCC cells, and overexpression Notch1's activated form (Notch intracellular domain) could rescue miR-935's tumor suppressive effect on GSRCC. Expression of miR-935 was lower in gastric carcinoma tissue than in paired normal tissue samples, and lower in GSRCC than in non-GSRCC. Our results demonstrate the inverse correlation between the expression of miR-935 and Notch1 in gastric tissues. We conclude that miR-935 inhibits gastric carcinoma cell proliferation, migration and invasion by targeting Notch1, suggesting potential applications of the miR-935-Notch1 pathway in gastric cancer clinical diagnosis and therapeutics, especially in gastric signet ring cell carcinoma. - Highlights: • The expression of miR-935 is lower in GC tissue than in paired normal tissue. • The expression of miR-935 is lower in GSRCC tissue than in non-GSRCC. • Enhanced expression of miR-935 suppresses tumorigenesis of GSRCC. • Notch1 is a direct target of miR-935.

  9. 160 Gb/s Raman-assisted notch-filtered XPM wavelength conversion and transmission

    Galili, Michael; Oxenløwe, Leif Katsuo; Mulvad, Hans Christian Hansen

    2007-01-01

    In-line wavelength conversion of 160 Gb/s data by Raman-assisted notch-filtered XPM is demonstrated for 130 km total transmission. The improvement in system performance from applying Raman gain during conversion is shown.......In-line wavelength conversion of 160 Gb/s data by Raman-assisted notch-filtered XPM is demonstrated for 130 km total transmission. The improvement in system performance from applying Raman gain during conversion is shown....

  10. Conditions for crack initiation in an orthotropic bi-material notch

    Klusák, Jan; Profant, T.; Kotoul, M.

    2012-01-01

    Roč. 19, č. 4 (2012), s. 302-307 ISSN 1537-6494 R&D Projects: GA ČR GA101/08/0994; GA ČR GAP108/10/2049 Institutional support: RVO:68081723 Keywords : General singular stress concentrators * Fracture mechanics * Notch es * Bi-material notch es * Fracture mechanics Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 0.701, year: 2012

  11. Opposing actions of endocannabinoids on cholangiocarcinoma growth is via the differential activation of Notch signaling

    Frampton, Gabriel; Coufal, Monique; Li, Huang; Ramirez, Jonathan; DeMorrow, Sharon

    2010-01-01

    The endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG) have opposing effects on cholangiocarcinoma growth. Implicated in cancer, Notch signaling requires the γ-secretase complex for activation. The aims of this study were to determine if the opposing effects of endocannabinoids depend on the differential activation of the Notch receptors and to demonstrate that the differential activation of these receptors are due to presenilin 1 containing- and presenilin 2 containing-γ-secretase complexes. Mz-ChA-1 cells were treated with AEA or 2-AG. Notch receptor expression, activation, and nuclear translocation were determined. Specific roles for Notch 1 and 2 on cannabinoid-induced effects were determined by transient transfection of Notch 1 or 2 shRNA vectors before stimulation with AEA or 2-AG. Expression of presenilin 1 and 2 was determined after AEA or 2-AG treatment, and the involvement of presenilin 1 and 2 in the cannabinoid-induced effects was demonstrated in cell lines with low presenilin 1 or 2 expression. Antiproliferative effects of AEA required increased Notch 1 mRNA, activation, and nuclear translocation, whereas the growth-promoting effects induced by 2-AG required increased Notch 2 mRNA expression, activation, and nuclear translocation. AEA increased presenilin 1 expression and recruitment into the γ-secretase complex, whereas 2-AG increased expression and recruitment of presenilin 2. The development of novel therapeutic strategies aimed at modulating the endocannabinoid system or mimicking the mode of action of AEA on Notch signaling pathways would prove beneficial for cholangiocarcinoma management.

  12. FOXP3 expression is modulated by TGF-β1/NOTCH1 pathway in human melanoma

    Skarmoutsou, Eva; Bevelacqua, Valentina; D'Amico, Fabio; Russo, Angela; Spandidos, Demetrios A.; Scalisi, Aurora

    2018-01-01

    Forkhead box protein 3 (FOXP3) transcription factor is expressed by immune cells and several human cancers and is associated with tumor aggressiveness and unfavorable clinical outcomes. NOTCH and transforming growth factor-β (TGF-β) protumorigenic effects are mediated by FOXP3 expression in several cancer models; however, their interaction and role in melanoma is unknown. We investigated TGF-β-induced FOXP3 gene expression during NOTCH1 signaling inactivation. Primary (WM35) and metastatic melanoma (A375 and A2058) cell lines and normal melanocytes (NHEM) were used. FOXP3 subcellular distribution was evaluated by immuno cytochemical analysis. Gene expression levels were assessed by reverse transcription-quantitative polymerase chain reaction. Protein levels were assessed by western blot analysis. The γ-secretase inhibitor (GSI) was used for NOTCH1 inhibition and recombinant human (rh)TGF-β was used for melanoma cell stimulation. Cell proliferation and viability were respectively assessed by MTT and Trypan blue dye assays. FOXP3 mRNA and protein levels were progressively higher in WM35, A375 and A2058 cell lines compared to NHEM and their levels were further increased after stimulation with rh-TGF-β. TGF-β-mediated FOXP3 expression was mediated by NOTCH1 signaling. Inhibition of NOTCH1 with concomitant rh-TGF-β stimulation determined the reduction in gene expression and protein level of FOXP3. Finally, melanoma cell line proliferation and viability were reduced by NOTCH1 inhibition. The results show that nn increase in FOXP3 expression in metastatic melanoma cell lines is a potential marker of tumor aggressiveness and metastasis. NOTCH1 is a central mediator of TGF-β-mediated FOXP3 expression and NOTCH1 inhibition produces a significant reduction of melanoma cell proliferation and viability. PMID:29620159

  13. TLX1 and NOTCH coregulate transcription in T cell acute lymphoblastic leukemia cells

    Riz, Irene; Hawley, Teresa S; Luu, Truong V; Lee, Norman H; Hawley, Robert G

    2010-01-01

    Abstract Background The homeobox gene TLX1 (for T-cell leukemia homeobox 1, previously known as HOX11) is inappropriately expressed in a major subgroup of T cell acute lymphoblastic leukemia (T-ALL) where it is strongly associated with activating NOTCH1 mutations. Despite the recognition that these genetic lesions cooperate in leukemogenesis, there have been no mechanistic studies addressing how TLX1 and NOTCH1 functionally interact to promote the leukemic phenotype. Results Global gene expre...

  14. Notch1 is a 5-fluorouracil resistant and poor survival marker in human esophagus squamous cell carcinomas.

    Jian Liu

    Full Text Available Notch signaling involves the processes that govern cell proliferation, cell fate decision, cell differentiation and stem cell maintenance. Due to its fundamental role in stem cells, it has been speculated during the recent years that Notch family may have critical functions in cancer stem cells or cancer cells with a stem cell phenotype, therefore playing an important role in the process of oncogenesis. In this study, expression of Notch family in KYSE70, KYSE140 and KYSE450 squamous esophageal cancer cell lines and virus transformed squamous esophageal epithelial cell line Het-1A was examined by quantitative RT-PCR. Compared to the Het-1A cells, higher levels of Nocth1 and Notch3 expression in the cancer cell lines were identified. Due to the finding that NOTCH3 mainly mediates squamous cell differentiation, NOTCH1 expression was further studied in these cell lines. By Western blot analyses, the KYSE70 cell line which derived from a poorly differentiated tumor highly expressed Notch1, and the Notch1 expression in this cell line was hypoxia inducible, while the KYSE450 cell line which derived from a well differentiated tumor was always negative for Notch1, even in hypoxia. Additional studies demonstrated that the KYSE70 cell line was more 5-FU resistant than the KYSE450 cell line and such 5-FU resistance is correlated to Notch1 expression verified by Notch1 knockdown experiments. In clinical samples, Notch1 protein expression was detected in the basal cells of human esophagus epithelia, and its expression in squamous cell carcinomas was significantly associated with higher pathological grade and shorter overall survival. We conclude that Notch1 expression is associated with cell aggressiveness and 5-FU drug resistance in human esophageal squamous cell carcinoma cell lines in vitro and is significantly associated with a poor survival in human esophageal squamous cell carcinomas.

  15. Subchondral bone density distribution in the human femoral head

    Wright, David A.; Meguid, Michael; Lubovsky, Omri; Whyne, Cari M. [Sunnybrook Research Institute, Orthopaedic Biomechanics Laboratory, Toronto, Ontario (Canada)

    2012-06-15

    This study aims to quantitatively characterize the distribution of subchondral bone density across the human femoral head using a computed tomography derived measurement of bone density and a common reference coordinate system. Femoral head surfaces were created bilaterally for 30 patients (14 males, 16 females, mean age 67.2 years) through semi-automatic segmentation of reconstructed CT data and used to map bone density, by shrinking them into the subchondral bone and averaging the greyscale values (linearly related to bone density) within 5 mm of the articular surface. Density maps were then oriented with the center of the head at the origin, the femoral mechanical axis (FMA) aligned with the vertical, and the posterior condylar axis (PCA) aligned with the horizontal. Twelve regions were created by dividing the density maps into three concentric rings at increments of 30 from the horizontal, then splitting into four quadrants along the anterior-posterior and medial-lateral axes. Mean values for each region were compared using repeated measures ANOVA and a Bonferroni post hoc test, and side-to-side correlations were analyzed using a Pearson's correlation. The regions representing the medial side of the femoral head's superior portion were found to have significantly higher densities compared to other regions (p < 0.05). Significant side-to-side correlations were found for all regions (r {sup 2} = 0.81 to r {sup 2} = 0.16), with strong correlations for the highest density regions. Side-to-side differences in measured bone density were seen for two regions in the anterio-lateral portion of the femoral head (p < 0.05). The high correlation found between the left and right sides indicates that this tool may be useful for understanding 'normal' density patterns in hips affected by unilateral pathologies such as avascular necrosis, fracture, developmental dysplasia of the hip, Perthes disease, and slipped capital femoral head epiphysis. (orig.)

  16. Image features of herniation pit of the femoral neck

    Zhang Xuezhe; Li Guangming; Wang Cunli; Wang Guimin

    2008-01-01

    Objective: To evaluate imaging appearances of herniation pit of the femoral neck. Methods: We retrospectively analyzed the X-ray, CT and MRI findings of 9 patients with herniation pit of the femoral neck. All nine patients were male with the age ranging from 21 to 73 years. They had pain in the hip from two months to two years duration. Results: The bilateral hips were affected in six patients, the right hips in the other 3 patients. Of the nine patients, X-ray plain films (2 cases), CT scanning(6 cases), and MR scanning (5 cases ) were performed. The size of the lesions ranged from 0.5 cm x 0.6 cm to 1.0 cm x 1.5 cm, located in the anterosuperior portion of the femoral neck (n=7) or anteroinferior portion (n=2). X-ray plain films showed an osteolytic lesion surrounded by a sclerotic rim. CT scanning showed the lesion just below the cortex of the femoral neck surrounded by a rim of sclerosis or associated with a small cortical break in two patients. MR scanning showed low signal intensity in five patients on T 1 WI and high signal intensity surrounded by a rim of low signal intensity (n=3) or low signal intensity (n=2) on T 2 WI, and high signal intensity on fat suppression MR image. A small joint effusion was observed in two cases on T 2 WI. Conclusion: The CT and MRI findings of herniation pit of the femoral neck are characteristic, it is useful in defining the diagnosis of the herniation pit of the femoral neck. (authors)

  17. Biophysical stimulation in osteonecrosis of the femoral head

    Massari Leo

    2009-01-01

    Full Text Available Osteonecrosis of the femoral head is the endpoint of a disease process that results from insufficient blood flow and bone-tissue necrosis, leading to joint instability, collapse of the femoral head, arthritis of the joint, and total hip replacement. Pain is the most frequent clinical symptom. Both bone tissue and cartilage suffer when osteonecrosis of the femoral head develops. Stimulation with pulsed electromagnetic fields (PEMFs has been shown to be useful for enhancing bone repair and for exerting a chondroprotective effect on articular cartilage. Two Italian studies on the treatment of avascular necrosis of the femoral head with PEMFs were presented in this review. In the first study, 68 patients suffering from avascular necrosis of the femoral head were treated with PEMFs in combination with core decompression and autologous bone grafts. The second one is a retrospective analysis of the results of treatment with PEMFs of 76 hips in 66 patients with osteonecrosis of the femoral head. In both studies clinical information and diagnostic imaging were collected at the beginning of the treatment and at the time of follow up. Statistical analysis was performed using chi-square test. Both authors hypothesize that the short-term effect of PEMF stimulation may be to protect the articular cartilage from the catabolic effect of inflammation and subchondral bone-marrow edema. The long-term effect of PEMF stimulation may be to promote osteogenic activity at the necrotic area and prevent trabecular fracture and subchondral bone collapse. PEMF stimulation represents an important therapeutic opportunity to resolve the Ficat stage-I or II disease or at least to delay the time until joint replacement becomes necessary.

  18. A potentiometric biosensor for the detection of notch 3 using functionalized ZnO nanorods.

    Ibupoto, Z H; Khun, K; Liu, X; Willander, M

    2014-09-01

    The notch signalling plays a vital and radical role for the activity of cellular proliferation, differentiation and apoptosis. In this study, for the first time a particular biosensor is developed for the detection of notch 3. ZnO nanorods were fabricated on the gold coated glass substrate by hydrothermal method and afterwards were decorated with the gold nanoparticles by electrodepositing technique. Scanning electron microscopy (SEM) has shown the perpendicular to the substrate growth pattern of ZnO nanorods. X-ray diffraction (XRD) studies showed the c-axis oriented growth direction with wurtzite crystal structure of ZnO nanorods. X-ray Photoelectron Spectroscopy (XPS) and energy dispersive X-ray (EDX) techniques have shown the presence of Zn, O and Au atoms in the prepared functional material. Furthermore, the anti-notch 3 was physically adsorbed on the gold nanoparticles functionalized ZnO nanorods. The developed potentiometric immunosensor has shown response to the wide range of notch 3 molecules. The detected range included 1.00 x 10(-5)-1.50 x 10(0 ) μg/mL with a sensitivity of 23.15 ± 0.31 mV/decade. The analytical parameters including reproducibility, stability, and selectivity were also investigated and the observed results indicate the acceptable performance of the notch 3 biosensor. Moreover, the proposed notch 3 biosensor exhibited a fast response time of 10 s.

  19. Modeling ductal carcinoma in situ: a HER2-Notch3 collaboration enables luminal filling.

    Pradeep, C-R

    2012-02-16

    A large fraction of ductal carcinoma in situ (DCIS), a non-invasive precursor lesion of invasive breast cancer, overexpresses the HER2\\/neu oncogene. The ducts of DCIS are abnormally filled with cells that evade apoptosis, but the underlying mechanisms remain incompletely understood. We overexpressed HER2 in mammary epithelial cells and observed growth factor-independent proliferation. When grown in extracellular matrix as three-dimensional spheroids, control cells developed a hollow lumen, but HER2-overexpressing cells populated the lumen by evading apoptosis. We demonstrate that HER2 overexpression in this cellular model of DCIS drives transcriptional upregulation of multiple components of the Notch survival pathway. Importantly, luminal filling required upregulation of a signaling pathway comprising Notch3, its cleaved intracellular domain and the transcriptional regulator HES1, resulting in elevated levels of c-MYC and cyclin D1. In line with HER2-Notch3 collaboration, drugs intercepting either arm reverted the DCIS-like phenotype. In addition, we report upregulation of Notch3 in hyperplastic lesions of HER2 transgenic animals, as well as an association between HER2 levels and expression levels of components of the Notch pathway in tumor specimens of breast cancer patients. Therefore, it is conceivable that the integration of the Notch and HER2 signaling pathways contributes to the pathophysiology of DCIS.

  20. Notch Filter Analysis and Its Application in Passive Coherent Location Radar (in English

    Li Ji-chuan

    2015-01-01

    Full Text Available The Normalized Least-Mean-Squares (NLMS algorithm is widely used to cancel the direct and multiple path interferences in Passive Coherent Location (PCL radar systems. This study proposes that the interference cancelation using the NLMS algorithm and the calculation of the radar Cross Ambiguity Function (CAF can be modeled as a notch filter, with the notch located at zero Doppler frequency in the surface of the radar CAF. The analysis shows that the notch’s width and depth are closely related to the step size of the NLMS algorithm. Subsequently, the effect of the notch in PCL radar target detection is analyzed. The results suggest that the detection performance of the PCL radar deteriorates because of the wide notch. Furthermore, the Nonuniform NLMS (NNLMS algorithm is proposed for removing the clutter with the Doppler frequency by using notch filtering. A step-size matrix is adopted to mitigate the low Doppler frequency clutter and lower the floor of the radar CAF. With the step-size matrix, can be obtained notches of different depths and widths in different range units of the CAF, which can filter the low Doppler frequency clutter. In addition, the convergence rate of the NNLMS algorithm is better than that of the traditional NLMS algorithm. The validity of the NNLMS algorithm is verified by experimental results.

  1. Plastic deformation and failure mechanisms in nano-scale notched metallic glass specimens under tensile loading

    Dutta, Tanmay; Chauniyal, Ashish; Singh, I.; Narasimhan, R.; Thamburaja, P.; Ramamurty, U.

    2018-02-01

    In this work, numerical simulations using molecular dynamics and non-local plasticity based finite element analysis are carried out on tensile loading of nano-scale double edge notched metallic glass specimens. The effect of acuteness of notches as well as the metallic glass chemical composition or internal material length scale on the plastic deformation response of the specimens are studied. Both MD and FE simulations, in spite of the fundamental differences in their nature, indicate near-identical deformation features. Results show two distinct transitions in the notch tip deformation behavior as the acuity is increased, first from single shear band dominant plastic flow localization to ligament necking, and then to double shear banding in notches that are very sharp. Specimens with moderately blunt notches and composition showing wider shear bands or higher material length scale characterizing the interaction stress associated with flow defects display profuse plastic deformation and failure by ligament necking. These results are rationalized from the role of the interaction stress and development of the notch root plastic zones.

  2. Insensible is a novel nuclear inhibitor of Notch activity in Drosophila.

    Franck Coumailleau

    Full Text Available Notch signalling regulates a wide range of developmental processes. In the Drosophila peripheral nervous system, Notch regulates a series of binary fate decisions that lead to the formation of regularly spaced sensory organs. Each sensory organ is generated by single sensory organ precursor cell (SOP via a series of asymmetric cell divisions. Starting from a SOP-specific Cis-Regulatory Module (CRM, we identified insensible (insb, a.k.a CG6520, as a SOP/neuron-specific gene encoding a nuclear factor that inhibits Notch signalling activity. First, over-expression of Insb led to the transcriptional repression of a Notch reporter and to phenotypes associated with the inhibition of Notch. Second, while the complete loss of insb activity had no significant phenotype, it enhanced the bristle phenotype associated with reduced levels of Hairless, a nuclear protein acting as a co-repressor for Suppressor of Hairless. In conclusion, our work identified Insb as a novel SOP/neuron-specific nuclear inhibitor of Notch activity in Drosophila.

  3. Stress Concentration Factor and Stress Intensity Factor with U-notch and Crack in the Beam

    Seo, Bo Seong; Lee, Kwang Ho [Kyungpook National Univ., Daegu (Korea, Republic of)

    2016-05-15

    The stress concentration factors and stress intensity factors for a simple beam and a cantilever are analyzed by using finite element method and photoelasticity. Using the analyzed results, the estimated graphs on stress concentration factors and stress intensity factors are obtained. To analyze stress concentration factors of notch, the dimensionless notch length H(height of specimen)/h=1.1-2 and dimensionless gap space r(radius at the notch tip)/h=0.1~0.5 are used, where h=H-c and c is the notch length. As the notch gap length increases and the gap decreases, the stress concentration factors increase. Stress concentration factors of a simple beam are greater than those of a cantilever beam. However, actually, the maximum stress values under a load, a notch length and a gap occur more greatly in the cantilever beam than in the simple beam. To analyze stress intensity factors, the normalized crack length α(crack length)/H=0.2~0.5 is used. As the length of the crack increases, the normalized stress intensity factors increase. The stress intensity factors under a constant load and a crack length occur more greatly in the cantilever beam than in the simple beam.

  4. Gamma-glutamylcyclotransferase promotes the growth of human glioma cells by activating Notch-Akt signaling

    Shen, Shang-Hang; Yu, Ning; Liu, Xi-Yao; Tan, Guo-Wei; Wang, Zhan-Xiang, E-mail: md_wzx7189@163.com

    2016-03-18

    Glioma as an aggressive type tumor is rapidly growing and has become one of the leading cause of cancer-related death worldwide. γ-Glutamylcyclotransferase (GGCT) has been shown as a diagnostic marker in various cancers. To reveal whether there is a correlation between GGCT and human glioma, GGCT expression in human glioma tissues and cell lines was first determined. We found that GGCT expression was up-regulated in human glioma tissues and cell lines. Further, we demonstrate that GGCT knockdown inhibits glioma cell T98G and U251 proliferation and colony formation, whereas GGCT overexpression leads to oppose effects. GGCT overexpression promotes the expression of Notch receptors and activates Akt signaling in glioma cells, and Notch-Akt signaling is activated in glioma tissues with high expression of GGCT. Finally, we show that inhibition of Notch-Akt signaling with Notch inhibitor MK-0752 blocks the effects of GGCT on glioma proliferation and colony formation. In conclusion, GGCT plays a critical role in glioma cell proliferation and may be a potential cancer therapeutic target. - Highlights: • GGCT expression is up-regulated in human glioma tissues and cell lines. • GGCT promotes glioma cell growth and colony formation. • GGCT promotes the activation of Notch-Akt signaling in glioma cells and tissues. • Notch inhibition blocks the role of GGCT in human glioma cells.

  5. Notch activates Wnt-4 signalling to control medio-lateral patterning of the pronephros.

    Naylor, Richard W; Jones, Elizabeth A

    2009-11-01

    Previous studies have highlighted a role for the Notch signalling pathway during pronephrogenesis in the amphibian Xenopus laevis, and in nephron development in the mammalian metanephros, yet a mechanism for this function remains elusive. Here, we further the understanding of how Notch signalling patterns the early X. laevis pronephros anlagen, a function that might be conserved in mammalian nephron segmentation. Our results indicate that early phase pronephric Notch signalling patterns the medio-lateral axis of the dorso-anterior pronephros anlagen, permitting the glomus and tubules to develop in isolation. We show that this novel function acts through the Notch effector gene hrt1 by upregulating expression of wnt4. Wnt-4 then patterns the proximal pronephric anlagen to establish the specific compartments that span the medio-lateral axis. We also identified pronephric expression of lunatic fringe and radical fringe that is temporally and spatially appropriate for a role in regulating Notch signalling in the dorso-anterior region of the pronephros anlagen. On the basis of these results, along with data from previous publications, we propose a mechanism by which the Notch signalling pathway regulates a Wnt-4 function that patterns the proximal pronephric anlagen.

  6. RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J.

    Wacker, Stephan Armin; Alvarado, Cristobal; von Wichert, Götz; Knippschild, Uwe; Wiedenmann, Jörg; Clauss, Karen; Nienhaus, Gerd Ulrich; Hameister, Horst; Baumann, Bernd; Borggrefe, Tilman; Knöchel, Walter; Oswald, Franz

    2011-01-05

    The evolutionarily conserved Notch signal transduction pathway regulates fundamental cellular processes during embryonic development and in the adult. Ligand binding induces presenilin-dependent cleavage of the receptor and a subsequent nuclear translocation of the Notch intracellular domain (NICD). In the nucleus, NICD binds to the recombination signal sequence-binding protein J (RBP-J)/CBF-1 transcription factor to induce expression of Notch target genes. Here, we report the identification and functional characterization of RBP-J interacting and tubulin associated (RITA) (C12ORF52) as a novel RBP-J/CBF-1-interacting protein. RITA is a highly conserved 36 kDa protein that, most interestingly, binds to tubulin in the cytoplasm and shuttles rapidly between cytoplasm and nucleus. This shuttling RITA exports RBP-J/CBF-1 from the nucleus. Functionally, we show that RITA can reverse a Notch-induced loss of primary neurogenesis in Xenopus laevis. Furthermore, RITA is able to downregulate Notch-mediated transcription. Thus, we propose that RITA acts as a negative modulator of the Notch signalling pathway, controlling the level of nuclear RBP-J/CBF-1, where its amounts are limiting.

  7. Effect of delaminations on improvement of notch toughness at low temperatures

    Zhou, W.; Loh, N.L.

    1996-01-01

    The notched-bar impact test is often used to assess the notch toughness of engineering materials. The principle of the test is that a material absorbs a certain amount of energy when it breaks; the energy thus absorbed is an indication of the material's resistance to impact fracture. If the material is brittle, it breaks easily with a small amount of absorbed energy. If it is tough, it will absorb more energy to fracture. It has been well recognized that most engineering materials undergo a transition from notch tough to notch brittle behavior when the temperature is reduced. In the present study, however, an abnormal trend in the transition behavior was found for an austenitic stainless steel. V-notched specimens of the steel were tested under impact loading in a wide temperature range from -196 C to room temperature. Contrary to expectation, the impact energy values obtained at low temperatures were found to be much higher than those obtained at room temperature, indicating that the steel became tougher rather than more brittle when the test temperature was lowered. This intriguing phenomenon cannot be explained simply according to the tensile stress fracture criterion. Strong evidence has been obtained in the present study to show that the improvement of notch toughness at low temperatures is caused by delaminations

  8. Theoretical and experimental study of Chen chaotic system with notch filter feedback control

    Ming, Zhang Xiao; Jian-Hua, Peng; Ju-Fang, Chen

    2010-01-01

    Since the past two decades, the time delay feedback control method has attracted more and more attention in chaos control studies because of its simplicity and efficiency compared with other chaos control schemes. Recently, it has been proposed to suppress low-dimensional chaos with the notch filter feedback control method, which can be implemented in a laser system. In this work, we have analytically determined the controllable conditions for notch filter feedback controlling of Chen chaotic system in terms of the Hopf bifurcation theory. The conditions for notch filter feedback controlled Chen chaoitc system having a stable limit cycle solution are given. Meanwhile, we also analysed the Hopf bifurcation direction, which is very important for parameter settings in notch filter feedback control applications. Finally, we apply the notch filter feedback control methods to the electronic circuit experiments and numerical simulations based on the theoretical analysis. The controlling results of notch filter feedback control method well prove the feasibility and reliability of the theoretical analysis. (general)

  9. Dwell Notch Low Cycle Fatigue Behavior of a Powder Metallurgy Nickel Disk Alloy

    Telesman, J.; Gabb, T. P.; Yamada, Y.; Ghosn, L. J.; Jayaraman, N.

    2012-01-01

    A study was conducted to determine the processes which govern dwell notch low cycle fatigue (NLCF) behavior of a powder metallurgy (P/M) ME3 disk superalloy. The emphasis was placed on the environmentally driven mechanisms which may embrittle the highly stressed notch surface regions and reduce NLCF life. In conjunction with the environmentally driven notch surface degradation processes, the visco-plastic driven mechanisms which can significantly change the notch root stresses were also considered. Dwell notch low cycle fatigue testing was performed in air and vacuum on a ME3 P/M disk alloy specimens heat treated using either a fast or a slow cooling rate from the solutioning treatment. It was shown that dwells at the minimum stress typically produced a greater life debit than the dwells applied at the maximum stress, especially for the slow cooled heat treatment. Two different environmentally driven failure mechanisms were identified as the root cause of early crack initiation in the min dwell tests. Both of these failure mechanisms produced mostly a transgranular crack initiation failure mode and yet still resulted in low NLCF fatigue lives. The lack of stress relaxation during the min dwell tests produced higher notch root stresses which caused early crack initiation and premature failure when combined with the environmentally driven surface degradation mechanisms. The importance of environmental degradation mechanisms was further highlighted by vacuum dwell NLCF tests which resulted in considerably longer NLCF lives, especially for the min dwell tests.

  10. ALK1 signaling inhibits angiogenesis by cooperating with the Notch pathway.

    Larrivée, Bruno; Prahst, Claudia; Gordon, Emma; del Toro, Raquel; Mathivet, Thomas; Duarte, Antonio; Simons, Michael; Eichmann, Anne

    2012-03-13

    Activin receptor-like kinase 1 (ALK1) is an endothelial-specific member of the TGF-β/BMP receptor family that is inactivated in patients with hereditary hemorrhagic telangiectasia (HHT). How ALK1 signaling regulates angiogenesis remains incompletely understood. Here we show that ALK1 inhibits angiogenesis by cooperating with the Notch pathway. Blocking Alk1 signaling during postnatal development in mice leads to retinal hypervascularization and the appearance of arteriovenous malformations (AVMs). Combined blockade of Alk1 and Notch signaling further exacerbates hypervascularization, whereas activation of Alk1 by its high-affinity ligand BMP9 rescues hypersprouting induced by Notch inhibition. Mechanistically, ALK1-dependent SMAD signaling synergizes with activated Notch in stalk cells to induce expression of the Notch targets HEY1 and HEY2, thereby repressing VEGF signaling, tip cell formation, and endothelial sprouting. Taken together, these results uncover a direct link between ALK1 and Notch signaling during vascular morphogenesis that may be relevant to the pathogenesis of HHT vascular lesions. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Stress fracture of the femoral neck in a child (stress fracture)

    Coldwell, D.; Gross, G.W.; Boal, D.K.

    1984-01-01

    Femoral neck stress fracture is extremely rare in childhood. We report a case of femoral neck stress fracture in an 11-year-old girl. Differentials diagnosis and a brief review of the literature follow. (orig.)

  12. The treatment of nonisthmal femoral shaft nonunions with im nail exchange versus augmentation plating.

    Park, Jin; Kim, Sul Gee; Yoon, Han Kook; Yang, Kyu Hyun

    2010-02-01

    The purpose of this study was to compare the results between exchange nailing (EN) and augmentation plating (AP) with a nail left in situ for nonisthmal femoral shaft nonunion after femoral nailing. : Retrospective data analysis, November 1996-March 2006. A level I trauma center. Eighteen patients with 18 nonisthmal femoral nonunions. Seven patients with 7 fractures treated for nonisthmal femoral shaft nonunions after femoral nailing with EN and 11 patients with 11 fractures treated for nonisthmal femoral shaft nonunions after nailing with AP combined with bone grafting. Union and complications. Five nonunions in the EN group failed to achieve union (72% failure rate), whereas all 11 pseudarthroses in the AP group obtained osseous union. Fisher exact test showed a higher nonunion rate of EN compared with AP for nonisthmal femoral shaft nonunion (odds ratio, 6.5; P = 0.002). AP with autogenous bone grafting may be a better option than EN for nonisthmal femoral nonunions.

  13. Automatic quantification of tibio-femoral contact area and congruity

    Tummala, Sudhakar; Nielsen, Mads; Lillholm, Martin

    2012-01-01

    We present methods to quantify the medial tibio- femoral (MTF) joint contact area (CA) and congruity index (CI) from low-field magnetic resonance imaging (MRI). Firstly, based on the segmented MTF cartilage compartments, we computed the contact area using the Euclidian distance transformation....... The CA was defined as the area of the tibial superior surface and the femoral inferior surface that are less than a voxel width apart. Furthermore, the CI is computed point-by-point by assessing the first- and second-order general surface features over the contact area. Mathematically, it is the inverse...

  14. Morfología femoral proximal en fracturas de cadera

    Calvo de Mora Rebollo, María Jesús; Albareda Albareda, Jorge Cruz; Seral García, Belén; Martín Ruiz, G.; Lasierra Sanromán, José Manuel; Seral Iñigo, Fernando

    2003-01-01

    Es frecuente observar como pacientes que han sufrido una fractura de cadera, si se fracturan posteriormente la cadera contralateral, es del mismo tipo que la primera fractura. El objetivo de este trabajo es tratar de relacional la morfología femoral proximal con la producción de un tipo determinado de fractura. Para ello hemos realizado un estudio prospectivo en 50 pacientes mayores de 65 años, sin distinción de sexo, que han ingresado en nuestro servicio por fractura femoral proximal, 25 ...

  15. Repair of femoral trochanteric osteotomy in the dog

    Whitelock, R.G.; Dyce, J.; Houlton, J.E.F.

    1997-01-01

    The records and radiographs of 24 dogs that underwent femoral trochanteric osteotomy repair were reviewed. Osteotomy repair was performed with either a pin and tension band wire or a lag screw technique. Significant clinical complications associated with the osteotomy were identified in one dog (4 per cent) six weeks after surgery, although abnormal radiographic changes were evident in 15 dogs (62 per cent). The method of repair did not influence healing and there were comparable radiographic complication rates. It is concluded that femoral trochanteric osteotomy is not associated with significant clinical problems, despite a high incidence of abnormal radiographic findings

  16. [SURGICAL HIP DISLOCATION APPROACH FOR TREATMENT OF FEMORAL HEAD FRACTURE].

    Tang, Yanfeng; Liu, Youwen; Zhu, Yingjie; Li, Jianming; Li, Wuyin; Li, Qiyi; Jia, Yudong

    2015-11-01

    To discuss the value of surgical hip dislocation approach in the treatment of femoral head fracture. A retrospectively analysis was made on the clinical data of 15 patients with femoral head fractures treated through surgical hip dislocation approach between January 2010 and February 2013. There were 11 men and 4 women with an average age of 30.8 years (range, 15-63 years). The causes included traffic accident injury in 9 cases, falling injury from height in 5 cases, and sports injury in 1 case. According to Pipkin typing, 2 cases were rated as type I, 7 cases as type II, 1 case as type III, and 5 cases as type IV. The interval of injury and operation was 2-10 days (mean, 4.1 days). Reduction was performed in 10 patients within 6 hours after injury, and then bone traction was given for 4-6 weeks except 5 patients who received reduction in the other hospital. Primary healing of incision was obtained in all patients after surgery without complications of dislocation and lower limbs deep venous thrombosis. The mean follow-up time was 29.9 months (range, 25-36 months). During follow-up, there was no infection, breakage of internal fixation, or nonunion of femoral greater trochanter fracture. In 3 patients having necrosis of the femoral head, 2 had no obvious symptoms [staging as IIa and IIb respectively according to Association Research Circulation Osseous (ARCO) staging system], and 1 (stage IIIb) had nonunion of the femoral neck fracture, who underwent total hip arthroplasty (THA). In 4 patients having myositis ossificans (2 cases of grade I, 1 case of grade II, and 1 case of grade III based on Brooker grading), no treatment was given in 3 cases and the focus was removed during THA in 1 case. According to the Thompson-Epstein scale at last follow-up, the results were excellent in 9 cases, good in 3 cases, fair in 1 case, and poor in 2 cases, and the excellent and good rate was 80%. Surgical hip dislocation approach can not only protect the residual vessels of the

  17. Medial circumflex femoral artery flap for ischial pressure sore

    Palanivelu S

    2009-01-01

    Full Text Available A new axial pattern flap based on the terminal branches of the medial circumflex femoral artery is described for coverage of ischial pressure sore. Based on the terminal branches of the transverse branch of medial circumflex femoral artery, which exit through the gap between the quadratus femoris muscle above and the upper border of adductor magnus muscle below, this fascio cutaneous flap is much smaller than the posterior thigh flap but extremely useful to cover ischeal pressure sores. The skin redundancy below the gluteal fold allows a primary closure of the donor defect. It can also be used in combination with biceps femoris muscle flap.

  18. Case of slipped capital femoral epiphysis following radiation

    Terada, Hiroshi; Usui, Hiroshi; Nakamura, Yutaka; Chiba, Masahiro; Yamaji, Shushin; Oba, Yoshihiro

    1987-06-01

    A 12-year-old boy presented with pain of the right hip joint and claudication. At the age of 7 months, the patient had received prophylactic irradiation of 30 Gy to the pelvic area including lumbar vertebrae and bilateral hip joints following extirpation of the right undescended testicle for embryonal carcinoma. Roentgenograph showed slipped capial femoral epiphysis. A review of the literature suggests that bone growth and hormonal changes in the early stage of puberty are involved, in addition to radiation damaged epiphyseal cartilage, in the pathophysiologic mechanisms of radiation induced slipped capital femoral epiphysis. (Namekawa, K.).

  19. Can femoral dialysis catheter insertion cause a life threatening complication?

    Nurkay Katrancıoğlu

    2014-09-01

    Full Text Available Venous catheter (VC insertion may be necessary for the patients with renal failure facing vascular access problem. Femoral VCs are commonly used for their lower complication rates especially in emergency clinics. The incidence of bleeding associated with VC is reported 0.5-1.6%, however, life threatening hemorrhage and complications requiring surgical intervention are very rare. In this manuscript, we aimed to present a case with hemolytic uremic syndrome complicated with retroperitoneal hematoma after femoral VC insertion. J Clin Exp Invest 2014; 5 (3: 472-474

  20. Postoperative hemoglobin level in patients with femoral neck fracture

    Nagra, Navraj; van Popta, Dmitri; Whiteside, Sigrid; Holt, Edward

    2018-01-01

    Objective: The aim of this study was to analyze the changes of hemoglobin levels in patients undergoing fixation for femoral neck fracture.Methods: Peroperative hemoglobin levels of patients who underwent either dynamic hip screw (DHS) fixation (n=74; mean age: 80 years) or hip hemiarthroplasty (n=104; mean age: 84 years) for femoral neck fracture was monitored.Results: There was a statistically and clinically significant mean drop of 31.1 g/L between the preoperative (D0) and postoperative D...

  1. Identification of avascular necrosis in the dysplastic proximal femoral epiphysis

    Mandell, G.A.; Harcke, H.T.; MacKenzie, W.G.; Bassett, G.S.; Scott, C.I. Jr.; Wills, J.S.

    1989-01-01

    Bilateral radiographic irregularities and deformities of the proximal femoral epiphyses are features of both multiple epiphyseal dysplasia and bilateral idiopathic avascular necrosis. In the past these entities have been difficult to differentiate. This report documents radiographically the occurrence of avascular necrosis in 10 patients with multiple epiphyseal dysplasia by recognizing the superimposition of sclerosis and subchondral fissuring on pre-existing symmetrically irregular proximal femoral ossification centers. Scintigraphic (photopenia) or magnetic resonance (loss of signal) criteria of avascular necrosis confirm its added presence and help to establish an imaging scheme to identify avascular necrosis superimposed on multiple epiphyseal dysplasia. (orig.)

  2. Avascular necrosis associated with nailing of femoral neck fracture

    Stroemqvist, B.; Hansson, L.I.

    1983-01-01

    Two patients with femoral neck fractures, one displaced and one undisplaced, are presented. Preoperative intravital staining with tetracycline and Tc-MDP scintimetry both showed intact femoral head circulation while Tc-MDP-scintimetry 1 week after operation showed pronounced circulatory deficiency. SR 85 -scintimetry performed at the same time was inconclusive. Segmental collapse was observed radiographically, 8 and 12 months postoperatively. The major vascular injury resulting in avascularity most probably occured during the procedure of osteosynthesis, and Tc-MDP-scintimetry was found suitable for early postoperative recognition of avascular necrosis in both fractures. (author)

  3. Identification of avascular necrosis in the dysplastic proximal femoral epiphysis

    Mandell, G A; Harcke, H T [Alfred I. duPont Inst., Wilmington, DE (USA). Dept. of Medical Imaging; MacKenzie, W G; Bassett, G S [Alfred I. duPont Inst., Wilmington, DE (USA). Dept. of Orthopaedics; Scott, Jr, C I [Alfred I. duPont Inst., Wilmington, DE (USA). Dept. of Genetics; Wills, J S [Medical Center of Delaware, Newark, DE (USA). Dept. of Radiology

    1989-07-01

    Bilateral radiographic irregularities and deformities of the proximal femoral epiphyses are features of both multiple epiphyseal dysplasia and bilateral idiopathic avascular necrosis. In the past these entities have been difficult to differentiate. This report documents radiographically the occurrence of avascular necrosis in 10 patients with multiple epiphyseal dysplasia by recognizing the superimposition of sclerosis and subchondral fissuring on pre-existing symmetrically irregular proximal femoral ossification centers. Scintigraphic (photopenia) or magnetic resonance (loss of signal) criteria of avascular necrosis confirm its added presence and help to establish an imaging scheme to identify avascular necrosis superimposed on multiple epiphyseal dysplasia. (orig.).

  4. Avascular necrosis associated with nailing of femoral neck fracture

    Stroemqvist, B; Hansson, L I [Department of Orthopaedic Surgery, University Hospital in Lund, Sweden

    1983-01-01

    Two patients with femoral neck fractures, one displaced and one undisplaced, are presented. Preoperative intravital staining with tetracycline and Tc-MDP scintimetry both showed intact femoral head circulation while Tc-MDP-scintimetry 1 week after operation showed pronounced circulatory deficiency. Sr/sup 85/-scintimetry performed at the same time was inconclusive. Segmental collapse was observed radiographically, 8 and 12 months postoperatively. The major vascular injury resulting in avascularity most probably occured during the procedure of osteosynthesis, and Tc-MDP-scintimetry was found suitable for early postoperative recognition of avascular necrosis in both fractures.

  5. [Ex vivo microCT analysis of possible microfractures of the femoral head during implantation of a cementless hip resurfacing femoral component].

    Lerch, M; Olender, G; von der Höh, N; Thorey, F; von Lewinski, G; Meyer-Lindenberg, A; Windhagen, H; Hurschler, C

    2009-01-01

    Microfractures of the femoral head during implantation of the femoral components are suspected to be a cause of fractures at the implant/neck junction which represent a common failure mode in hip resurfacing arthroplasty. Callus formation observed in femoral head retrievals suggests the occurrence of microfractures inside the femoral head, which might be inadvertently caused by the surgeon during implantation. The aim of this biomechanical study was to analyse whether or not the implantation of a cementless femoral component hip resurfacing system causes microfractures in the femoral head. After the preparation of 20 paired human cadaveric femoral heads, the cementless femoral component ESKA Typ BS (ESKA Implants GmbH & Co., Lübeck) was implanted on 9 specimens with an impaction device that generates 4.5 kN impaction force. On 9 specimens the femoral component was implanted by hand. One head was used as a fracture model, 1 specimen served as control without manipulation. The femoral component used for impaction was equipped with hinges to enable its removal without further interfering with the bone stock. Specimens were scanned with a microCT device before and after impaction and the microCT datasets before and after impaction were compared to identify possible microfractures. Twenty strikes per hand or with the impaction device provided sufficient implant seating. Neither the macroscopic examination nor the 2-dimensional microCT analysis revealed any fractures of the femoral heads after impaction. At least macroscopically and in the 2-dimensional microCT analysis, implantation of the cementless hip resurfacing femoral component ESKA Typ BS with 4.5 kN or by hand does not seem to cause fractures of the femoral head. Georg Thieme Verlag KG Stuttgart, New York.

  6. Early detection by sup(99m)Tc-Sn-pyrophosphate scintigraphy of femoral head necrosis following medial femoral neck fractures

    Greiff, J.; Lanng, S.; Hoeilund-Carlsen, P.F.; Karle, A.K.; Uhrenholdt, A.

    1980-01-01

    A selected series of 24 patients with displaced medial femoral neck fracture, treated with closed reduction and osteosynthesis with cancellous bone screws (ASIF), were investigated. During an observation period of 6 to 26 months, serial hip joint scintigraphies were performed and compared with serial X-ray examinations. At the first scintigraphic examination performed on average 5-6 weeks after the fracture, two separate investigators found a decreased amount of activity or no activity in the femoral head of 10 and 8 patients, respectively. At the second scintigraphic examination performed on average 11.1 weeks after the fracture both investigators found no activity or a decreased amount of activity in 8 patients. This figure declined to 7 during the following period, because one patient with decreased activity was recorded as having normal activity 15 months after the fracture. These 7 patients all developed radiological signs of femoral head collapse on average 16.3 months after the fracture (range 5-26 months), whereas their scintigrams displayed decreased or absent tracer uptake on average 1.2 months after the fracture (P<0.01). None of the patients with initially normal or increased uptake later showed decreased or absent uptake during the study and none developed radiological collapse. It may be concluded that absent or decreased uptake of sup(99m)Tc-Sn-pyrophosphate in the femoral head following medial femoral neck fracture indicates femoral head necrosis and a high risk of late segmental collapse, whereas normal or increased uptake implying preserved blood supply means that late segmental collapse will probably never develop. (author)

  7. Face detection and facial feature localization using notch based templates

    Qayyum, U.

    2007-01-01

    We present a real time detection off aces from the video with facial feature localization as well as the algorithm capable of differentiating between the face/non-face patterns. The need of face detection and facial feature localization arises in various application of computer vision, so a lot of research is dedicated to come up with a real time solution. The algorithm should remain simple to perform real time whereas it should not compromise on the challenges encountered during the detection and localization phase, keeping simplicity and all challenges i.e. algorithm invariant to scale, translation, and (+-45) rotation transformations. The proposed system contains two parts. Visual guidance and face/non-face classification. The visual guidance phase uses the fusion of motion and color cues to classify skin color. Morphological operation with union-structure component labeling algorithm extracts contiguous regions. Scale normalization is applied by nearest neighbor interpolation method to avoid the effect of different scales. Using the aspect ratio of width and height size. Region of Interest (ROI) is obtained and then passed to face/non-face classifier. Notch (Gaussian) based templates/ filters are used to find circular darker regions in ROI. The classified face region is handed over to facial feature localization phase, which uses YCbCr eyes/lips mask for face feature localization. The empirical results show an accuracy of 90% for five different videos with 1000 face/non-face patterns and processing rate of proposed algorithm is 15 frames/sec. (author)

  8. Evaluation in femoral neck fracture scintimetry: modes of region of interest selection and influence on results

    Holmberg, S.; Mesko, L.; Stroemqvist, B.; Thorngren, K.G.

    1985-04-01

    Different sized ROIs within the femoral head and different modes of calculation were used in (/sup 99m/Tc)MDP scintimetry after femoral neck fracture. In preoperative scintimetry, correction for increased trochanteric uptake gave the best discrimination, whereas in postoperative scintimetry the direct ratio fractured/intact femoral head was superior. The change in ROI size had little influence.

  9. Evaluation in femoral neck fracture scintimetry: modes of region of interest selection and influence on results

    Holmberg, S.; Mesko, L.; Stroemqvist, B.; Thorngren, K.G.

    1985-01-01

    Different sized ROIs within the femoral head and different modes of calculation were used in [/sup 99m/Tc]MDP scintimetry after femoral neck fracture. In preoperative scintimetry, correction for increased trochanteric uptake gave the best discrimination, whereas in postoperative scintimetry the direct ratio fractured/intact femoral head was superior. The change in ROI size had little influence

  10. The stability of the femoral component of a minimal invasive total hip replacement system.

    Willems, M.M.M.; Kooloos, J.G.M.; Gibbons, P.; Minderhoud, N.; Weernink, T.; Verdonschot, N.J.J.

    2006-01-01

    In this study, the initial stability of the femoral component of a minimal invasive total hip replacement was biomechanically evaluated during simulated normal walking and chair rising. A 20 mm diameter canal was created in the femoral necks of five fresh frozen human cadaver bones and the femoral

  11. 21 CFR 888.3360 - Hip joint femoral (hemi-hip) metallic cemented or uncemented prosthesis.

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hip joint femoral (hemi-hip) metallic cemented or... Hip joint femoral (hemi-hip) metallic cemented or uncemented prosthesis. (a) Identification. A hip joint femoral (hemi-hip) metallic cemented or uncemented prosthesis is a device intended to be implanted...

  12. 21 CFR 888.3400 - Hip joint femoral (hemi-hip) metallic resurfacing prosthesis.

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hip joint femoral (hemi-hip) metallic resurfacing... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3400 Hip joint femoral (hemi-hip) metallic resurfacing prosthesis. (a) Identification. A hip joint femoral (hemi-hip...

  13. Factors that influence femoral neck length. Analysis of 1543 patients with advanced osteoarthritis of the hip

    Prins, Wybren; Kollen, Boudewijn J.; Ettema, Harmen B.; Verheyen, Cees C. P. M.

    2013-01-01

    Background and purpose: There is little known about the relationship between patient characteristic and the variance in geometrical properties of the femoral neck. The length of the femoral neck is relevant when considering a femoral neck preserving hip replacement. Based on surgical experience we

  14. 21 CFR 888.3570 - Knee joint femoral (hemi-knee) metallic uncemented prosthesis.

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Knee joint femoral (hemi-knee) metallic uncemented... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3570 Knee joint femoral (hemi-knee) metallic uncemented prosthesis. (a) Identification. A knee joint femoral (hemi-knee...

  15. Estimated carotid-femoral pulse wave velocity has similar predictive value as measured carotid-femoral pulse wave velocity

    Olsen, Michael; Greve, Sara; Blicher, Marie

    2016-01-01

    OBJECTIVE: Carotid-femoral pulse wave velocity (cfPWV) adds significantly to traditional cardiovascular (CV) risk prediction, but is not widely available. Therefore, it would be helpful if cfPWV could be replaced by an estimated carotid-femoral pulse wave velocity (ePWV) using age and mean blood...... pressure and previously published equations. The aim of this study was to investigate whether ePWV could predict CV events independently of traditional cardiovascular risk factors and/or cfPWV. DESIGN AND METHOD: cfPWV was measured and ePWV calculated in 2366 apparently healthy subjects from four age...

  16. V-notch tip subjected to in-plane mixed mode loading: overview of recent results and possible future outcomes

    F. Berto

    2017-07-01

    Full Text Available . The fictitious notch rounding concept is applied for the first time to V-notches with root hole subjected to in-plane mixed mode loading. Outof-bisector crack propagation is taken into account. The fictitious notch radius is determined as a function of the real notch radius, the microstructural support length and the notch opening angle. Due to the complexity of the problem, a method based on the simple normal stress failure criterion has been used. It is combined with the maximum tangential stress criterion to determine the crack propagation angle. An analytical method based on Neuber's procedure has been developed. The method provides the values of the microstructural support factor as a function of the mode ratio and the notch opening angle. The support factor is considered to be independent of the microstructural support length. Finally, for comparison, the support factor is determined on a purely numerical basis by iterative analysis of FE models.

  17. The Research Progress of SiRNA Targeting Notch1 on Tumor Cells: A Mini Review of the State of the Art

    Lanfen Huo

    2016-09-01

    Full Text Available Notch signaling is a highly conserved signaling pathway, playing an important role in a variety of cell differentiation, development and regulation. Notch signaling includes Notch1-4; Notch1 gene encodes Notch1 signaling that can shorten cell cycle, enhance cell proliferation, inhibit cell differentiation, and promote apoptosis. Mutation and overexpression of the Notch1 gene may induce tumorigenesis, which plays an important role in the development of tumors across a variety of signaling pathways. Currently, using RNA interference technology (RNAi synthesizing small interference RNA (siRNA targeting Notch1 gene(siNotch1)has become a hot topic, and clinical application of gene silencing has also obtained a certain therapeutic effect. In this paper, the application of Notch1 gene silencing in tumor progress was reviewed.

  18. A FUNCTIONAL EVALUATION STUDY OF DISTAL FEMORAL FRACTURES FIXED WITH DISTAL FEMORAL LOCKING PLATE

    Manikumar C. J

    2017-04-01

    Full Text Available BACKGROUND Fractures of the distal femur present considerable challenges in management. Older patients especially women sustain fractures due to osteoporosis. Supracondylar fractures of femur have a bimodal distribution. They account for 6% of all femur fractures and 31% if hip fractures were excluded. Nearly, 50% of distal femur intra-articular fractures are open fractures. Before 1970, most supracondylar fractures were treated nonoperatively; however, difficulties were often encountered including persistent angulatory deformity, knee joint incongruity, loss of knee motion and delayed mobilisation. The trend of open reduction and internal fixation has become evident in recent years with good results being obtained with AO blade plate, dynamic condylar screw, intramedullary supracondylar nail and locking compression plate. Elderly patients and osteoporosis pose difficulty in treating intra-articular fractures of the lower end of femur. Loss of stable fixation is of great concern in these cases. Hence, locking compression plate use has an advantage in these patients. MATERIALS AND METHODS In this study, 20 patients with closed fracture of distal femur were studied. All the cases were treated at the Department of Orthopaedics, Rangaraya Medical College/Government General Hospital, Kakinada, Andhra Pradesh, between November 2013 and November 2015. The method used for fracture fixation was open reduction and internal fixation with distal femoral locking plate. The duration of follow up ranged from 3 months to 24 months. All the fractures in this series were posttraumatic. The patients were functionally evaluated with Neer’s scoring system. 1 RESULTS Twenty distal femoral fractures were treated with distal femoral locking plates. 15 patients were males and 5 patients were females. The median age was 47 years ranging from 28-70 years. 16 of the fractures were caused by road traffic accidents and 2 were due to fall, 2 were due to assault. 12 patients

  19. An expanded Notch-Delta model exhibiting long-range patterning and incorporating MicroRNA regulation.

    Jerry S Chen

    2014-06-01

    Full Text Available Notch-Delta signaling is a fundamental cell-cell communication mechanism that governs the differentiation of many cell types. Most existing mathematical models of Notch-Delta signaling are based on a feedback loop between Notch and Delta leading to lateral inhibition of neighboring cells. These models result in a checkerboard spatial pattern whereby adjacent cells express opposing levels of Notch and Delta, leading to alternate cell fates. However, a growing body of biological evidence suggests that Notch-Delta signaling produces other patterns that are not checkerboard, and therefore a new model is needed. Here, we present an expanded Notch-Delta model that builds upon previous models, adding a local Notch activity gradient, which affects long-range patterning, and the activity of a regulatory microRNA. This model is motivated by our experiments in the ascidian Ciona intestinalis showing that the peripheral sensory neurons, whose specification is in part regulated by the coordinate activity of Notch-Delta signaling and the microRNA miR-124, exhibit a sparse spatial pattern whereby consecutive neurons may be spaced over a dozen cells apart. We perform rigorous stability and bifurcation analyses, and demonstrate that our model is able to accurately explain and reproduce the neuronal pattern in Ciona. Using Monte Carlo simulations of our model along with miR-124 transgene over-expression assays, we demonstrate that the activity of miR-124 can be incorporated into the Notch decay rate parameter of our model. Finally, we motivate the general applicability of our model to Notch-Delta signaling in other animals by providing evidence that microRNAs regulate Notch-Delta signaling in analogous cell types in other organisms, and by discussing evidence in other organisms of sparse spatial patterns in tissues where Notch-Delta signaling is active.

  20. Notch1 deficiency in postnatal neural progenitor cells in the dentate gyrus leads to emotional and cognitive impairment.

    Feng, Shufang; Shi, Tianyao; Qiu, Jiangxia; Yang, Haihong; Wu, Yan; Zhou, Wenxia; Wang, Wei; Wu, Haitao

    2017-10-01

    It is well known that Notch1 signaling plays a crucial role in embryonic neural development and adult neurogenesis. The latest evidence shows that Notch1 also plays a critical role in synaptic plasticity in mature hippocampal neurons. So far, deeper insights into the function of Notch1 signaling during the different steps of adult neurogenesis are still lacking, and the mechanisms by which Notch1 dysfunction is associated with brain disorders are also poorly understood. In the current study, we found that Notch1 was highly expressed in the adult-born immature neurons in the hippocampal dentate gyrus. Using a genetic approach to selectively ablate Notch1 signaling in late immature precursors in the postnatal hippocampus by cross-breeding doublecortin (DCX) + neuron-specific proopiomelanocortin (POMC)-α Cre mice with floxed Notch1 mice, we demonstrated a previously unreported pivotal role of Notch1 signaling in survival and function of adult newborn neurons in the dentate gyrus. Moreover, behavioral and functional studies demonstrated that POMC-Notch1 -/- mutant mice showed anxiety and depressive-like behavior with impaired synaptic transmission properties in the dentate gyrus. Finally, our mechanistic study showed significantly compromised phosphorylation of cAMP response element-binding protein (CREB) in Notch1 mutants, suggesting that the dysfunction of Notch1 mutants is associated with the disrupted pCREB signaling in postnatally generated immature neurons in the dentate gyrus.-Feng, S., Shi, T., Qiu, J., Yang, H., Wu, Y., Zhou, W., Wang, W., Wu, H. Notch1 deficiency in postnatal neural progenitor cells in the dentate gyrus leads to emotional and cognitive impairment. © FASEB.