Editorial Commentary: The All-Epiphyseal Anterior Cruciate Ligament Distal Femoral Approach: Sockets or Tunnels?

Science.gov (United States)

Cordasco, Frank A

2018-05-01

I believe that the distal femoral approach for anterior cruciate ligament reconstruction in the skeletally immature athlete with 3 to 6 years of remaining growth is best performed with an all-inside, all-epiphyseal technique using sockets rather than an outside-in approach creating tunnels. A shorter socket rather than a longer tunnel exposes a smaller surface area of the lateral distal femoral physis to potential compromise and resultant valgus malalignment. In addition, exiting the lateral femoral aspect of the epiphysis with a full-diameter tunnel as compared with a smaller diameter drill hole used to prepare a socket places the posterior articular cartilage, the lateral collateral ligament and anterolateral ligament footprints, and the popliteus tendon insertion at risk. My preference for sockets is also related to my belief that they provide a superior biologic milieu for graft incorporation compared with a full-length tunnel with the attendant violation of the lateral femoral cortex of the epiphysis. Copyright © 2018 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

The Direct Anterior Approach Does Not Increase Return to Function Following Hemiarthroplasty for Femoral Neck Fracture.

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Carlson, Victor R; Ong, Alvin C; Orozco, Fabio R; Lutz, Rex W; Duque, Andres F; Post, Zachary D

2017-11-01

The purpose of this study was to evaluate functional outcomes for hemiarthroplasty using a direct anterior approach or a direct lateral approach for femoral neck fracture. This retrospective review used data collected from a single institution between 2006 and 2016. Eighty-five and 75 consecutive patients who underwent hemiarthroplasty via a direct anterior approach and a direct lateral approach, respectively, met inclusion criteria. All patients with femoral neck fractures were treated by 1 of 2 fellowship-trained orthopedic surgeons using the direct anterior approach or the direct lateral approach to hemiarthroplasty. Disposition, ambulation, and other perioperative surgical outcomes were compared between the cohorts. Compared with the direct lateral cohort, the direct anterior cohort had a shorter mean operative time (2.4 minutes, P<.01), a shorter mean length of hospital stay (2.7 days, P<.01), and a smaller mean decrease in hemoglobin postoperatively (0.7 g/dL, P<.01). No significant difference was observed between the cohorts for postoperative disposition, the number of feet ambulated on the second postoperative day, or the prevalence of ambulatory decline at 4- to 6-week and 4- to 6-month follow-up visits. Compared with the direct lateral approach, the direct anterior approach may benefit patients by small, but statistically significant, improvements in blood loss, surgical time, and length of hospital stay after hemiarthroplasty. However, the direct anterior approach does not appear to decrease the likelihood of transfer to a skilled nursing facility postoperatively or accelerate return to preoperative function. [Orthopedics. 2017; 40(6):e1055-e1061.]. Copyright 2017, SLACK Incorporated.

Anterior Femoral Bow and Possible Effect on the Stifle Joint: A Comparison between Humans and Dogs.

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Ocal, M K; Sabanci, S S; Cobanoglu, M; Enercan, M

2017-08-01

The aim of the study was to compare the anterior bow of the femur between dogs and humans in terms of the possible impact on the stifle joint. The femoral radiographs obtained retrospectively were used to determine the angles and positions of the anterior bow in both dogs (n = 135) and humans (n = 57). Descriptive statistics and Pearson's correlation analysis were used for the statistical analyses of the variables. The mean anterior bow angle (ABA) was 18.3 ± 2.02° and 4.88 ± 1.24° in dogs and humans, respectively. The bow position was at the distal shaft in dogs (64.9 ± 2.04%) and almost at the mid-shaft of the bone (46.5 ± 5.52%) in humans. The ABA was related to the bow position in both humans and dogs. Additionally, the angle correlated with age in humans, while it was correlated with weight and breed in dogs. In conclusion, it is suggested that the anterior bow should be used as a landmark on the femoral axis for the biomechanical research of stifle joint, and dog stifle could be used as a suitable model for human knee in experimental studies for clinicians, while making sure that ethical principles are fully respected. © 2017 Blackwell Verlag GmbH.

Anterior approach versus posterior approach for Pipkin I and II femoral head fractures: A systemic review and meta-analysis.

Science.gov (United States)

Wang, Chen-guang; Li, Yao-min; Zhang, Hua-feng; Li, Hui; Li, Zhi-jun

2016-03-01

We performed a meta-analysis, pooling the results from controlled clinical trials to compare the efficiency of anterior and posterior surgical approaches to Pipkin I and II fractures of the femoral head. Potential academic articles were identified from the Cochrane Library, Medline (1966-2015.5), PubMed (1966-2015.5), Embase (1980-2015.5) and ScienceDirect (1966-2015.5) databases. Gray studies were identified from the references of the included literature. Pooling of the data was performed and analyzed by RevMan software, version 5.1. Five case-control trials (CCTs) met the inclusion criteria. There were significant differences in the incidence of heterotopic ossification (HO) between the approaches, but no significant differences were found between the two groups regarding functional outcomes of the hip, general postoperative complications, osteonecrosis of the femoral head or post-traumatic arthritis. The present meta-analysis indicated that the posterior approach decreased the risk of heterotopic ossification compared with the anterior approach for the treatment of Pipkin I and II femoral head fractures. No other complications were related to anterior and posterior approaches. Future high-quality randomized, controlled trials (RCTs) are needed to determine the optimal surgical approach and to predict other postoperative complications. III. Copyright © 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

[Postoperative analgesia in knee arthroplasty using an anterior sciatic nerve block and a femoral nerve block].

Science.gov (United States)

del Fresno Cañiaveras, J; Campos, A; Galiana, M; Navarro-Martínez, J A; Company, R

2008-11-01

To evaluate the efficacy of a nerve block as an alternative technique for analgesia after knee arthroplasty and to indicate the usefulness and advantages of the anterior approach to the sciatic nerve block. Between April 2004 and March 2006, we studied a series of consecutive patients undergoing knee arthroplasty in which a subarachnoid block was used as the anesthetic technique and postoperative analgesia was provided by means of a combined peripheral femoral nerve block and an anterior sciatic nerve block. We evaluated the mean length of time free from pain, quality of analgesia, and length of stay in hospital. Seventy-eight patients were included in the study. The mean (SD) length of time free from pain for the group was 42.1 (3.9) hours. Patients reported mild pain after 34.8 (4.1) hours and moderate to severe pain after 42.4 (3.5) hours. By the third day, 62.8% of patients were able to bend the knee to 90 degrees. There were no complications resulting from the technique and the level of patient satisfaction was high. A combined femoral-sciatic nerve block is effective in knee arthroplasty. It controls postoperative pain and allows for early rehabilitation. The anterior approach to the sciatic nerve is relatively simple to perform without removing the pressure bandaging from the thigh after surgery. This approach also makes it unnecessary to move the patient.

Prevalence and clinical significance of chondromalacia isolated to the anterior margin of the lateral femoral condyle as a component of patellofemoral disease: observations at MR imaging.

LENUS (Irish Health Repository)

Chan, V O

2013-08-01

To determine the prevalence of chondromalacia isolated to the anterior margin of the lateral femoral condyle as a component of patellofemoral disease in patients with anterior knee pain and to correlate it with patient demographics, patellar shape, and patellofemoral alignment.

Femoral intertrochanteric nail (fitn): a new short version design with an anterior curvature and a geometric match study using post-operative radiographs.

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Chang, Shi-Min; Hu, Sun-Jun; Ma, Zhuo; Du, Shou-Chao; Zhang, Ying-Qi

2018-02-01

Femoral intertrochanteric fractures are usually fixed with short, straight cephalomedullary nails. However, mismatches between the nail and the femur frequently occur, such as tip impingement and tail protrusion. The authors designed a new type of short femoral intertrochanteric nail (fitn) with an anterior curvature (length=19.5cm, r=120cm) and herein report the geometric match study for the first of 50 cases. A prospective case series of 50 geriatric patients suffering from unstable intertrochanteric fractures (AO/OTA 31 A2/3) were treated. There were 15 males and 35 females, with an average age of 82.3 years. Post-operatively, the nail entry point position in the sagittal greater trochanter (in three categories, anterior, central and posterior), the nail-tip position in the medullary canal (in 5-grade scale) and the nail-tail level to the greater trochanter (in 3-grade scale) were measured using X-ray films. For the nail entry point measurement, 5 cases were anterior (10%), 38 cases were central (76%), and 7 cases were posterior (14%). For the distal nail-tip position, 32 cases (64%) were located along the central canal axis, 13 cases (26%) were located anteriorly but did not contact the anterior inner cortex, 2 cases (4%) showed less than one-third anterior cortex thickness contact, and 3 cases (6%) were located posteriorly with no contact. For the proximal nail-tail level, there were no protrusions over the greater trochanter in 15 cases (30%), protrusion of less than 5mm in 29 cases (58%), and protrusion of more than 5mm in 6 cases (12%). The fitness was very high, as 96% cases showed no tip-cortex contact, and 88% cases showed less than 5mm proximal tail protrusion. The newly designed femoral intertrochanteric nail has a good geometric match with the femur medullary canal and the proximal length in the Chinese population. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparing low volume saphenous-obturator block with placebo and femoral-obturator block for anterior cruciate ligament reconstruction: a randomized controlled trial

DEFF Research Database (Denmark)

Lenz, Katja; Jensen, Kenneth; Tanggaard, Katrine

2018-01-01

BACKGROUND: Anterior cruciate ligament reconstruction (ACL-RC) is often associated with moderate to severe postoperative pain even with a multimodal analgesic regimen. We aimed to compare the analgesic efficacy of low volume saphenous-obturator block with placebo and femoral- obturator block in p...

Advantages and Disadvantages of Transtibial, Anteromedial Portal, and Outside-In Femoral Tunnel Drilling in Single-Bundle Anterior Cruciate Ligament Reconstruction: A Systematic Review.

Science.gov (United States)

Robin, Brett N; Jani, Sunil S; Marvil, Sean C; Reid, John B; Schillhammer, Carl K; Lubowitz, James H

2015-07-01

Controversy exists regarding the best method for creating the knee anterior cruciate ligament (ACL) femoral tunnel or socket. The purpose of this study was to systematically review the risks, benefits, advantages, and disadvantages of the endoscopic transtibial (TT) technique, anteromedial portal technique, outside-in technique, and outside-in retrograde drilling technique for creating the ACL femoral tunnel. A PubMed search of English-language studies published between January 1, 2000, and February 17, 2014, was performed using the following keywords: "anterior cruciate ligament" AND "femoral tunnel." Included were studies reporting risks, benefits, advantages, and/or disadvantages of any ACL femoral technique. In addition, references of included articles were reviewed to identify potential studies missed in the original search. A total of 27 articles were identified through the search. TT technique advantages include familiarity and proven long-term outcomes; disadvantages include the risk of nonanatomic placement because of constrained (TT) drilling. Anteromedial portal technique advantages include unconstrained anatomic placement; disadvantages include technical challenges, short tunnels or sockets, and posterior-wall blowout. Outside-in technique advantages include unconstrained anatomic placement; disadvantages include the need for 2 incisions. Retrograde drilling technique advantages include unconstrained anatomic placement, as well as all-epiphyseal drilling in skeletally immature patients; disadvantages include the need for fluoroscopy for all-epiphyseal drilling. There is no one, single, established "gold-standard" technique for creation of the ACL femoral socket. Four accepted techniques show diverse and subjective advantages, disadvantages, risks, and benefits. Level V, systematic review of Level II through V evidence. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Notch activates Wnt-4 signalling to control medio-lateral patterning of the pronephros.

Science.gov (United States)

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.

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

Science.gov (United States)

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

Effect of medial–lateral malpositioning of the femoral component in total knee arthroplasty on anterior knee pain at greater than 8 years of follow-up

NARCIS (Netherlands)

van de Groes, S.A.W.; Koëter, S.; De Waal Malefijt, M.C.; Verdonschot, Nicolaas Jacobus Joseph

2014-01-01

Background The trochlea is often medialized after total knee arthroplasty (TKA) resulting in abnormal patellar tracking, which may lead to anterior knee pain. However, due to the difference in shape of the natural trochlea and the patellar groove of the femoral component, a medialization of the

Pseudointercondylar notch sign: manifestation of osteochondritis dissecans of the trochlea

International Nuclear Information System (INIS)

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.)

Patellar tendon-lateral femoral condyle friction syndrome: MR imaging in 42 patients

International Nuclear Information System (INIS)

Chung, C.B.; Skaf, A.; Campos, J.; Stump, X.; Resnick, D.; Roger, B.

2001-01-01

Objective: To demonstrate the MR imaging findings that occur between the posterior inferolateral patellar tendon and the lateral femoral condyle in patients with chronic anterior and or lateral knee pain. Patients and design: A retrospective review of the MR images in 42 patients who presented with chronic anterior or lateral knee pain was performed by two musculoskeletal radiologists. In 15 patients, post-contrast images were available. Results: Sagittal and axial imaging planes best demonstrated the patellar tendon and its relationship with the lateral femoral condyle. In 40 patients, there was obliteration of the fat planes and abnormal signal intensity in the lateral soft tissues of the inferior patellofemoral joint. Enhancement after administration of gadolinium was noted in all cases in which contrast was administered. Eighteen patients showed cystic changes in the soft tissues adjacent to the lateral femoral condyle in addition to fat plane obliteration. In two patients, only cystic changes were noted in the lateral soft tissues. Abnormal patellar alignment was noted in 37 patients. Patellar tendon pathology was seen in nine patients. Conclusion: In evaluating anterior knee symptoms, MR imaging allows identification of changes that may be related to patellar tendon-lateral femoral condyle friction syndrome and that should be distinguished from other causes of anterior or lateral knee pain. (orig.)

Patellar tendon-lateral femoral condyle friction syndrome: MR imaging in 42 patients

Energy Technology Data Exchange (ETDEWEB)

Chung, C.B.; Skaf, A.; Campos, J.; Stump, X.; Resnick, D. [Dept. of Radiology, University of California, San Diego (United States); Roger, B. [Service de Radiologie Polyvalente, Groupe Hospitalier Pitie-Salpetriere, Paris (France)

2001-12-01

Objective: To demonstrate the MR imaging findings that occur between the posterior inferolateral patellar tendon and the lateral femoral condyle in patients with chronic anterior and or lateral knee pain. Patients and design: A retrospective review of the MR images in 42 patients who presented with chronic anterior or lateral knee pain was performed by two musculoskeletal radiologists. In 15 patients, post-contrast images were available. Results: Sagittal and axial imaging planes best demonstrated the patellar tendon and its relationship with the lateral femoral condyle. In 40 patients, there was obliteration of the fat planes and abnormal signal intensity in the lateral soft tissues of the inferior patellofemoral joint. Enhancement after administration of gadolinium was noted in all cases in which contrast was administered. Eighteen patients showed cystic changes in the soft tissues adjacent to the lateral femoral condyle in addition to fat plane obliteration. In two patients, only cystic changes were noted in the lateral soft tissues. Abnormal patellar alignment was noted in 37 patients. Patellar tendon pathology was seen in nine patients. Conclusion: In evaluating anterior knee symptoms, MR imaging allows identification of changes that may be related to patellar tendon-lateral femoral condyle friction syndrome and that should be distinguished from other causes of anterior or lateral knee pain. (orig.)

The hippo pathway promotes Notch signaling in regulation of cell differentiation, proliferation, and oocyte polarity.

Directory of Open Access Journals (Sweden)

Jianzhong Yu

2008-03-01

Full Text Available Specification of the anterior-posterior axis in Drosophila oocytes requires proper communication between the germ-line cells and the somatically derived follicular epithelial cells. Multiple signaling pathways, including Notch, contribute to oocyte polarity formation by controlling the temporal and spatial pattern of follicle cell differentiation and proliferation. Here we show that the newly identified Hippo tumor-suppressor pathway plays a crucial role in the posterior follicle cells in the regulation of oocyte polarity. Disruption of the Hippo pathway, including major components Hippo, Salvador, and Warts, results in aberrant follicle-cell differentiation and proliferation and dramatic disruption of the oocyte anterior-posterior axis. These phenotypes are related to defective Notch signaling in follicle cells, because misexpression of a constitutively active form of Notch alleviates the oocyte polarity defects. We also find that follicle cells defective in Hippo signaling accumulate the Notch receptor and display defects in endocytosis markers. Our findings suggest that the interaction between Hippo and classic developmental pathways such as Notch is critical to spatial and temporal regulation of differentiation and proliferation and is essential for development of the body axes in Drosophila.

A three-dimensional analysis of the sigmoid notch

Directory of Open Access Journals (Sweden)

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.

Arthroscopic treatment of femoral nerve paresthesia caused by an acetabular paralabral cyst.

Science.gov (United States)

Kanauchi, Taira; Suganuma, Jun; Mochizuki, Ryuta; Uchikawa, Shinichi

2014-05-01

This report describes a rare case of femoral nerve paresthesia caused by an acetabular paralabral cyst of the hip joint. A 68-year-old woman presented with a 6-month history of right hip pain and paresthesia along the anterior thigh and radiating down to the anterior aspect of the knee. Radiography showed osteoarthritis with a narrowed joint space in the right hip joint. Magnetic resonance imaging showed a cyst with low T1- and high T2-weighted signal intensity arising from a labral tear at the anterior aspect of the acetabulum. The cyst was connected to the joint space and displaced the femoral nerve to the anteromedial side. The lesion was diagnosed as an acetabular paralabral cyst causing femoral neuropathy. Because the main symptom was femoral nerve paresthesia and the patient desired a less invasive procedure, arthroscopic labral repair was performed to stop synovial fluid flow to the paralabral cyst that was causing the femoral nerve paresthesia. After surgery, the cyst and femoral nerve paresthesia disappeared. At the 18-month follow-up, the patient had no recurrence. There have been several reports of neurovascular compression caused by the cyst around the hip joint. To the authors' knowledge, only 3 cases of acetabular paralabral cysts causing sciatica have been reported. The current patient appears to represent a rare case of an acetabular paralabral cyst causing femoral nerve paresthesia. The authors suggest that arthroscopic labral repair for an acetabular paralabral cyst causing neuropathy can be an option for patients who desire a less invasive procedure. Copyright 2014, SLACK Incorporated.

Patellofemoral dysbalance and genua valga: outcome after femoral varisation osteotomies.

Science.gov (United States)

Dickschas, Jörg; Ferner, Felix; Lutter, Christoph; Gelse, Kolja; Harrer, Jörg; Strecker, Wolf

2018-01-01

Patellofemoral dysbalance may be caused by trochlear dysplasia, an elevated TTTG distance, femoral or tibial torsional deformities, patella alta, or a genu valgum. The surgical procedure for the treatment of a genu valgum is varisation osteotomy, usually in the femoral aspect. Several authors believe that a genu valgum is one cause of patellofemoral dysbalance, but studies about the outcome of the treatment with a varisation osteotomy are rare. Nineteen knees in 18 patients, aged on average 28 (16-52) years were investigated in a retrospective study. The patients had symptoms of patellofemoral instability or anterior knee pain due to a genu valgum, without symptoms of a lateral femorotibial compartment. All patients underwent a femoral varisation osteotomy. The diagnostic investigation prior to surgery included full-leg radiographs and torsional angle CT scans. The pre-surgery and follow-up investigation included the visual analog scale (VAS), the Kujala score, the Japanese Knee Society score, the Lysholm score. The mean duration of follow-up was 44(10-132) months. The mean preoperative mechanical valgus was 5.6° (range 4-10°). Twelve patients mentioned patellar instability as the main symptom while 14 mentioned anterior knee pain. No redislocation occurred in the follow-up period. Anterior knee pain on the VAS (p value patellofemoral dysbalance, treatment of this condition is femoral varisation osteotomy. In this study, patellofemoral stability was achieved and anterior knee pain was significantly reduced. Significant improvements in clinical scores proved the success of the treatment. IV, case series.

The cyclops lesion after bicruciate-retaining total knee replacement

OpenAIRE

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...

Variability in the range of inter-anterior superior iliac spine distance and its correlation with femoral head centre. A prospective computed tomography study of 200 adults

International Nuclear Information System (INIS)

Mullaji, Arun; Shetty, Gautam M.; Kanna, Raj; Sharma, Amit

2010-01-01

The anterior superior iliac spine (ASIS) is commonly used to estimate the centre of the femoral head and assess limb alignment during surgical procedures. This study aimed to determine the range of inter-anterior superior iliac spine distances (IADs) and inter-femoral head centre distances (IFDs) among individuals and ascertain whether there is correlation between the IFD and the IAD. We also sought to determine whether gender, height and body mass index (BMI) had any influence on IAD and IFD. We prospectively measured IAD and IFD in 200 adults, using transverse computed tomography (CT) scans done for medical causes. We also calculated the distance between the pelvic midline and the centre of the femoral head (XY distance) from the measured IFD. The influence of gender, height and body-mass index on IAD and IFD, and the correlation of IAD with IFD, were also studied. The overall mean IAD, IFD and XY distances were 22.7 ± 1.6 cm, 16.0 ± 0.8 cm and 8.0 ± 0.4 cm, respectively. There was wide variation within the IAD range with 50% (100/200) of the subjects having their IAD within ±10 mm of the mean compared to 75.5% (151/200) of the subjects with IFD within ±10 mm of the mean. The probability that the mean XY distance would fall within 10 mm of the true femoral head centre in all subjects was 100%. The gender difference in IAD and IFD was statistically significant (P = 0.03 and P < 0.001, respectively), height and BMI had no influence, and the correlation of IAD with IFD was weak (0.35). Although the range of IADs showed wide variation among subjects, this study clearly demonstrated the narrow range of the XY distance and IFD in the study population and provides a useful and accurate basis for a new method to determine the femoral head centre clinically and intraoperatively. (orig.)

All-Epiphyseal Anterior Cruciate Ligament Femoral Tunnel Drilling: Avoiding Injury to the Physis, Lateral Collateral Ligament, Anterolateral Ligament, and Popliteus-A 3-Dimensional Computed Tomography Study.

Science.gov (United States)

Shea, Kevin G; Cannamela, Peter C; Fabricant, Peter D; Terhune, Elizabeth B; Polousky, John D; Milewski, Matthew D; Anderson, Allen F; Ganley, Theodore J

2018-01-25

To investigate the relation of the at-risk structures (distal femoral physis, lateral collateral ligament, anterolateral ligament, popliteus, and articular cartilage) during all-epiphyseal femoral tunnel drilling. A second purpose was 2-fold: (1) to develop recommendations for tunnel placement and orientation that anatomically reconstruct the anterior cruciate ligament (ACL) while minimizing the risk of injury to these at-risk structures, and (2) to allow for maximal tunnel length to increase the amount of graft in the socket to facilitate healing. Three-dimensional models of 6 skeletally immature knees (aged 7-11 years) were reconstructed from computed tomography and used to simulate all-epiphyseal femoral tunnels. Tunnels began within the ACL footprint and were directed laterally or anterolaterally, with the goal of avoiding injury to at-risk structures. The spatial relation between the ideal tunnel and these structures was evaluated. Full-length tunnels and partial length condyle sockets were simulated in the models using the same trajectories. An anterolateral tunnel could be placed to avoid direct injury to lateral structures. The safe zone on the anterolateral aspect of the femur was larger than that of a tunnel with a direct lateral trajectory (median 127 mm 2 vs 83 mm 2 , P = .028). Anterolateral tunnels were longer than direct lateral tunnels (median 30 mm vs 24 mm, P = .041). Safe angles for anterolateral tunnels were 34° to 40° from the posterior condylar axis; direct lateral tunnels were drilled 4° to 9° from the posterior condylar axis. Sockets could be placed without direct injury to structures at risk with either orientation. An all-epiphyseal ACL femoral tunnel can be placed without causing direct injury to at-risk structures. A tunnel angled anterolaterally from the ACL origin is longer and has a larger safe zone compared with the direct lateral tunnel. The largest safe zone for femoral all-epiphyseal ACL drilling was (1) anterior to

Fracture of the acetabulum with femoral artery injury presenting late: A case report

Directory of Open Access Journals (Sweden)

Sivaprasad Kalyanasundaram

2016-02-01

Full Text Available This study reports a rare case of both column acetabulum fracture with femoral artery injury that presented late and was managed with arterial reconstruction and fracture fixation.A thirty-one year old man sustained both column acetabular fracture on the left in a motor vehicle accident. On admission there was no obvious neuro-vascular deficit. During surgery for the fracture after 7 days of the injury the femoral artery was found to be severely crushed with no blood flow. The anterior column of the acetabulum was stabilised followed by resection and reconstruction of the femoral artery. The post-operative period was uneventful and he was discharged normally. At 6 months from injury the fractures had united well with excellent limb circulation and good lower limb function.Femoral artery injury with acetabular fracture is rare and late presentations are unreported hitherto. The results of fracture stabilisation and vessel reconstruction seem to be excellent. Literature of similar injuries is reviewed. Keywords: Acetabular fractures, Both column fractures, Anterior column fractures, Vascular injury, Femoral artery injury

Reliability and reproducibility of several methods of arthroscopic assessment of femoral tunnel position during anterior cruciate ligament reconstruction.

Science.gov (United States)

Ilahi, Omer A; Mansfield, David J; Urrea, Luis H; Qadeer, Ali A

2014-10-01

To assess interobserver and intraobserver agreement of estimating anterior cruciate ligament (ACL) femoral tunnel positioning arthroscopically using circular and linear (noncircular) estimation methods and to determine whether overlay template visual aids improve agreement. Standardized intraoperative pictures of femoral tunnel pilot holes (taken with a 30° arthroscope through an anterolateral portal at 90° of knee flexion with horizontal being parallel to the tibial surface) in 27 patients undergoing single-bundle ACL reconstruction were presented to 3 fellowship-trained arthroscopists on 2 separate occasions. On both viewings, each surgeon estimated the femoral tunnel pilot hole location to the nearest half-hour mark using a whole clock face and half clock face, to the nearest 15° using a whole compass and half compass, in the top or bottom half of a linear quadrant, and in the top or bottom half of a linear trisector. Evaluations were performed first without and then with an overlay template of each estimation method. The average difference among reviewers was quite similar for all 4 circular methods with the use of visual aids. Without overlay template visual aids, pair-wise κ statistic values for interobserver agreement ranged from -0.14 to 0.56 for the whole clock face and from 0.16 to 0.42 for the half clock face. With overlay visual guides, interobserver agreement ranged from 0.29 to 0.63 for the whole clock face and from 0.17 to 0.66 for the half clock face. The quadrant method's interobserver agreement ranged from 0.22 to 0.60, and that of the trisection method ranged from 0.17 to 0.57. Neither linear estimation method's reliability uniformly improved with the use of overlay templates. Intraobserver agreement without overlay templates ranged from 0.17 to 0.49 for the whole clock face, 0.11 to 0.47 for the half clock face, 0.01 to 0.66 for the quadrant method, and 0.20 to 0.57 for the trisection method. Use of overlay templates did not uniformly

Femoral sizing in total knee arthroplasty is rotation dependant.

Science.gov (United States)

Koninckx, Angelique; Deltour, Arnaud; Thienpont, Emmanuel

2014-12-01

The mismatch between the medio-lateral (ML) and the antero-posterior (AP) size of femoral components in total knee arthroplasty (TKA) has been linked to gender, ethnicity, morphotype and height differences in patients. The hypothesis of this study was that the AP size measurement of a femoral component increases with more external rotation in posterior referencing TKA. During a 2-year period, 201 patients were included in this prospective study. The AP distance of the distal femur was measured with an AP sizer of the Vanguard (Biomet, Warsaw, US) knee system. This AP sizer allows to dial in external rotation by 1° increments and to determine the femoral size with an anterior boom. AP size was noted at 0°, 3° and 5° of external rotation and then compared for ML matching. Antero-posterior and corresponding ML sizes match perfectly for the Vanguard at 0° of external rotation and a central boom position on the anterior femoral surface. Then, the anterior boom was positioned on the antero-lateral cortex and the AP size increased a mean (SD) 1 (0.5) mm. With 3° of external rotation, the AP size increased a mean (SD) 2.3 (0.4) mm and for 5° a mean (SD) 3.8 (0.3) mm (P external rotation that is dialled in during surgery. Since these parameters vary case per case, the availability of narrow components offers more surgical options to the surgeon and its importance extends beyond the gender aspect allowing different amounts of external rotation to be used without ML overhang. II.

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

Science.gov (United States)

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.

Computerized tomography in evaluation of decreased acetabular and femoral anteversion

International Nuclear Information System (INIS)

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

Inhibition of myostatin signaling through Notch activation following acute resistance exercise.

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Matthew G MacKenzie

Full Text Available Myostatin is a TGFβ family member and negative regulator of muscle size. Due to the complexity of the molecular pathway between myostatin mRNA/protein and changes in transcription, it has been difficult to understand whether myostatin plays a role in resistance exercise-induced skeletal muscle hypertrophy. To circumvent this problem, we determined the expression of a unique myostatin target gene, Mighty, following resistance exercise. Mighty mRNA increased by 6 h (82.9 ± 24.21% and remained high out to 48 h (56.5 ± 19.67% after resistance exercise. Further examination of the soleus, plantaris and tibialis anterior muscles showed that the change in Mighty mRNA at 6 h correlated with the increase in muscle size associated with this protocol (R(2 = 0.9996. The increase in Mighty mRNA occurred both independent of Smad2 phosphorylation and in spite of an increase in myostatin mRNA (341.8 ± 147.14% at 3 h. The myostatin inhibitor SKI remained unchanged. However, activated Notch, another potential inhibitor of TGFβ signaling, increased immediately following resistance exercise (83 ± 11.2% and stayed elevated out to 6 h (78 ± 16.6%. Electroportion of the Notch intracellular domain into the tibialis anterior resulted in an increase in Mighty mRNA (63 ± 13.4% that was equivalent to the canonical Notch target HES-1 (94.4 ± 7.32%. These data suggest that acute resistance exercise decreases myostatin signaling through the activation of the TGFβ inhibitor Notch resulting in a decrease in myostatin transcriptional activity that correlates well with muscle hypertrophy.

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

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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.

Myositis ossificans within the intercondylar notch treated arthroscopically

International Nuclear Information System (INIS)

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.)

Myositis ossificans within the intercondylar notch treated arthroscopically

Energy Technology Data Exchange (ETDEWEB)

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.)

ACL graft can replicate the normal ligament's tension curve

NARCIS (Netherlands)

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

Correlation between Focal Nodular Low Signal Changes in Hoffa’s Fat Pad Adjacent to Anterior Femoral Cartilage and Focal Cartilage Defect Underlying This Region and Its Possible Implication

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Chermaine Deepa Antony

2016-01-01

Full Text Available Purpose. This study investigates the association between focal nodular mass with low signal in Hoffa’s fat pad adjacent to anterior femoral cartilage of the knee (FNMHF and focal cartilage abnormality in this region. Method. The magnetic resonance fast imaging employing steady-state acquisition sequence (MR FIESTA sagittal and axial images of the B1 and C1 region (described later of 148 patients were independently evaluated by two reviewers and categorized into four categories: normal, FNMHF with underlying focal cartilage abnormality, FNMHF with normal cartilage, and cartilage abnormality with no FNMHF. Results. There was a significant association (p=0.00 between FNMHF and immediate adjacent focal cartilage abnormality with high interobserver agreement. The absence of focal nodular lesions next to the anterior femoral cartilage has a very high negative predictive value for chondral injury (97.8%. Synovial biopsy of focal nodular lesion done during arthroscopy revealed some fibrocollagenous tissue and no inflammatory cells. Conclusion. We postulate that the FNMHF adjacent to the cartilage defects is a form of normal healing response to the cartilage damage. One patient with FHMHF and underlying cartilage abnormality was rescanned six months later. In this patient, the FNMHF disappeared and normal cartilage was observed in the adjacent region which may support this theory.

Comparative study on anterior cruciate ligament reconstruction: determination of isometric points with and without navigation

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Fabio J. Angelini

2010-01-01

Full Text Available OBJECTIVES: To compare the accuracy of tunnel placement and graft isometry for anterior cruciate ligament reconstruction performed using a computer-assisted navigation system (Orthopilot and using traditional instruments. METHODS: The anterior cruciate ligament was removed intact from 36 pairs of human cadaver knees. From each pair, one knee was randomized to Group 1 (conventional and the other to Group 2 (Orthopilot. An inelastic suture was then passed through the central points of the tibial and femoral tunnels. Neither of the tunnels was drilled. All knees were then dissected, and six parameters were obtained: distances from the tibial tunnel center to the 1 posterior cruciate ligament, 2 anterior horn of the lateral meniscus and 3 medial tibial spine; 4 distance from the femoral tunnel center to the posterior femoral cortex; 5 femoral tunnel coronal angle; and 6 variation of the distance from the femoral to the tibial tunnel with the knee extended and at 90 degrees of flexion. RESULTS: The variation of the distance from the femoral to the tibial tunnel during flexion and extension was smaller in the Orthopilot group (better isometry compared to the conventional group. There were no statistical differences in any other parameters between the groups, and all tunnels were considered to be in satisfactory positions. DISCUSSION: The results obtained for anterior cruciate ligament reconstruction depend on precise isometric point positioning, and a navigation system is a precision tool that can assist surgeons in tunnel positioning. CONCLUSION: No differences in tunnel position were observed between the groups. Nonetheless, better isometry was achieved in the Orthopilot group than with conventional instruments.

MR imaging of anterior cruciate ligament tears: is there a gender gap?

International Nuclear Information System (INIS)

Fayad, Laura M.; Parellada, J.Antoni; Parker, Laurence; Schweitzer, Mark E.

2003-01-01

Clinically, females receive anterior cruciate ligament (ACL) tears more commonly than males. We explored whether gender differences exist in MR imaging patterns of ACL tears. At 1.5T, two observers evaluated MR examinations of 84 consecutive age-matched patients (42 males, 42 females, aged 16-39) with ACL tears, for mechanism of injury, extent and type of tear, the presence of secondary signs and associated osseous, meniscal and ligamentous injuries. The most common mechanism of injury for both females and males was the pivot shift mechanism (67 and 60%, respectively). Females were more commonly imaged in the acute stage of tear than males (98 and 67%, respectively, p=0.001) and more commonly possessed the typical posterolateral tibial bone contusion pattern (88 and 62%, respectively, p=0.0131). Males exhibited a deeper femoral notch sign (2.7 and 2.0 mm, p=0.007) and medial meniscal, lateral collateral ligament and posterior cruciate ligament injuries more commonly than females (48 and 24%, p=0.009, 30 and 7%, p=0.035, 17 and 0%, p=0.035). There was no significant difference between genders for the presence of other secondary signs and contusion patterns, associated lateral meniscal tears, presence of O'Donoghue's triad or associated medial collateral ligament injuries. Gender differences in MR imaging patterns of ACL tears exist: females are more commonly imaged in the acute stage and more commonly possess posterolateral tibial bone contusions; males have a more severe presentation than females, associated with more severe lateral femoral condyle and soft tissue injuries. (orig.)

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

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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.

Ranking of computed tomography in diagnosis of avascular necrosis of femoral head in adults

Energy Technology Data Exchange (ETDEWEB)

Nebel, G

1982-01-01

On 12 patients (7 males, 5 females) with the diagnosis of avascular (aseptic) necrosis of the femoral head the value of computed tomography was investigated. Stages II-IV were observed (following the staging of Ficat and Arlet). Exept for 2 cases the findings of necrosis on axial CT-slices were always located in the anterior part of the femoral head. The problems of early diagnosis of the disease are discussed.

Anatomic landmarks of fluoroscopy guided puncture of the pulseless femoral artery

International Nuclear Information System (INIS)

Jeon, Min Hee; Han, Gi Seok; Kim, Sung Jin; Park, Kil Sun; Cha, Sang Hoon; Bae, Il Hun; Lee, Seung Young

2006-01-01

We wanted to improve puncturing the pulseless femoral artery by evaluating the anatomic landmarks that suggest the course of the femoral artery on fluoroscopy. We analyzed 37 hemipelvis spot images that were centered on the arterial sheath after puncture of the femoral artery. The inguinal angles were measured between the inguinal line connecting the anterior superior iliac spine and the symphysis pubis, and the line of the arterial sheath. Inguinal ligament ratios were measured as the distance from the symphysis pubis to the arterial sheath to the length of the inguinal ligament on the inguinal line. The femoral head ratios were measured as the distance from the medial margin of the femur head to the arterial sheath to the transverse length of the femur head. The mean inguinal angle was 66.5 and the mean inguinal ligament ratio was 0.42 (± 0.03). The mean femoral head ratio was 0.08 (± 0.18). In comparing the men and women, there was no significant difference in the inguinal angle and the femoral head ratio, but the inguinal distance ratio was larger in women (men: 0.41 ± 0.033, women: 0.44 ± 0.031, ρ < 0.05). The femoral artery generally courses just lateral to the medial margin of the femur head (femoral head ratio: 0.08) and the medial 40% of the inguinal ligament (inguinal ligament ratio: 0.42). So, consideration of these relations may be helpful for puncturing the pulseless femoral artery

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

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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.

Ranking of computed tomography in diagnosis of avascular necrosis of femoral head in adults

International Nuclear Information System (INIS)

Nebel, G.

1982-01-01

On 12 patients (7 males, 5 females) with the diagnosis of avascular (aseptic) necrosis of the femoral head the value of computed tomography was investigated. Stages II-IV were observed (following the staging of Ficat and Arlet). Exept for 2 cases the findings of necrosis on axial CT-slices were always located in the anterior part of the femoral head. The problems of early diagnosis of the disease are discussed. (orig.) [de

Femoral neck fracture following groin irradiation

Energy Technology Data Exchange (ETDEWEB)

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.

Femoral neck fracture following groin irradiation

International Nuclear Information System (INIS)

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

Femoral neck pseudoarthrosis in a polio patient treated with closed reduction and cell therapy

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M.A. Codesido

2017-04-01

Full Text Available Poliomyelitis disease affects the anterior horns cells of the spinal cord and certain motor nuclei of the brain stem. Paralysis type is flaccid and asymmetrical and result in muscular imbalance.Due to this, in case of having a hip muscles involvement, degenerative or posttraumatic, total hip arthroplasty is normally contraindicated because of the excessive risk of hip dislocation. In cases of subcapital femoral neck fractures the femoral head vascularization is a main concern, and in cases of neglected fracture with pseudoarthrosis the vascular status to the head must be investigated prior to further decisions.We report the case of a femoral neck fracture non-union after a missed femoral neck fracture in a polio affected leg treated with cannulated screws and percutaneous autologous injection of processed total nuclear cells (TNC mixed with putty demineralized bone matrix. Keywords: Pseudoarthrosis, Poliomyelitis, Cell therapy, Femoral neck

Femoral Head Avascular Necrosis Is Not Caused by Arthroscopic Posterolateral Femoroplasty.

Science.gov (United States)

Rupp, Robert E; Rupp, Sasha N

2016-05-01

This study was conducted to identify the risk of avascular necrosis of the femoral head after arthroscopic femoroplasty extending to the posterolateral femoral neck, the source of the primary blood supply to the femoral head. Cam lesions of femoroacetabular impingement are typically anterior along the junction of the femoral head and neck. However, anatomic variations can involve the posterolateral vascular region of the femoral head and neck. Femoroplasty involving this vascular region can lead to injury to the blood supply to the femoral head, with subsequent avascular necrosis. If the posterolateral portion of the cam lesion is preserved, persistent femoroacetabular impingement may occur. A retrospective review identified 112 patients who underwent arthroscopic femoroplasty for femoroacetabular impingement over a 2-year period. Of these patients, 14 had femoroplasty that extended to the posterolateral femoral head. Of this group, 5 had undergone magnetic resonance imaging (MRI) after femoroplasty and the other 9 were contacted to undergo MRI of the hip to evaluate for avascular necrosis. A radiologist and the senior author evaluated all MRI scans specifically for avascular necrosis of the femoral head. All procedures were performed by the senior author. Mean age of the 14 patients (8 women and 6 men) with femoroplasty that extended into the posterolateral vascular region of the femoral head was 44 years (range, 23-69 years). All 14 patients underwent MRI evaluation of the affected hip a mean of 25 months (range, 7-44 months) after femoroplasty. No MRI scans showed evidence of avascular necrosis of the femoral head. Femoroplasty of the posterolateral vascular region of the femoral head is not associated with avascular necrosis. Patients with femoroacetabular impingement and a cam lesion extending to the posterolateral femoral head can undergo femoroplasty of this region without the development of avascular necrosis. [Orthopedics. 2016; 39(3):177-180.]. Copyright

Anterior cruciate ligament tears: MRI versus arthroscopy

International Nuclear Information System (INIS)

Tosch, U.; Felix, R.; Schauwecker, W.; Dreithaler, B.

1992-01-01

Because of suspected rupture of the anterior cruciate ligament sixteen acute traumatised patients were investigated by MR and arthroscopy. The MR diagnosis of a lesion of the anterior cruciate ligament proved to be correct by arthroscopy in fifteen of sixteen cases. Diagnostic criteria for lesions of the anterior cruciate ligament were: increased signal intensity in T 1 - and T 2 weighted images, increased volume and discontinuity of ligamentous structures. Additional MR findings of meniscal tears were correct in three of four cases laterally and in four of four cases medially. Femoral cartilage lesions were correctly identified by MR in three cases. MR normal findings proved to be correct by arthroscopy in another five cases. (orig.) [de

Transient Femoral Nerve Palsy Complicating “Blind” Transversus Abdominis Plane Block

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Dimitrios K. Manatakis

2013-01-01

Full Text Available We present two cases of patients who reported quadriceps femoris weakness and hypoesthesia over the anterior thigh after an inguinal hernia repair under transversus abdominis plane (TAP block. Transient femoral nerve palsy is the result of local anesthetic incorrectly injected between transversus abdominis muscle and transversalis fascia and pooling around the femoral nerve. Although it is a minor and self-limiting complication, it requires overnight hospital stay and observation of the patients. Performing the block under ultrasound guidance and injecting the least volume of local anesthetic required are ways of minimizing its incidence.

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

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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.

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

NARCIS (Netherlands)

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

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

OpenAIRE

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 ...

The cyclops lesion after bicruciate-retaining total knee replacement

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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

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

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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.

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

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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

Kinematic analysis of anterior cruciate ligament reconstruction in total knee arthroplasty

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Liu, Hua-Wei; Ni, Ming; Zhang, Guo-Qiang; Li, Xiang; Chen, Hui; Zhang, Qiang; Chai, Wei; Zhou, Yong-Gang; Chen, Ji-Ying; Liu, Yu-Liang; Cheng, Cheng-Kung; Wang, Yan

2016-01-01

Background: This study aims to retain normal knee kinematics after knee replacement surgeries by reconstructing anterior cruciate ligament during total knee arthroplasty. Method: We use computational simulation tools to establish four dynamic knee models, including normal knee model, posterior cruciate ligament retaining knee model, posterior cruciate ligament substituting knee model, and anterior cruciate ligament reconstructing knee model. Our proposed method utilizes magnetic resonance images to reconstruct solid bones and attachments of ligaments, and assemble femoral and tibial components according representative literatures and operational specifications. Dynamic data of axial tibial rotation and femoral translation from full-extension to 135 were measured for analyzing the motion of knee models. Findings: The computational simulation results show that comparing with the posterior cruciate ligament retained knee model and the posterior cruciate ligament substituted knee model, reconstructing anterior cruciate ligament improves the posterior movement of the lateral condyle, medial condyle and tibial internal rotation through a full range of flexion. The maximum posterior translations of the lateral condyle, medial condyle and tibial internal rotation of the anterior cruciate ligament reconstructed knee are 15.3 mm, 4.6 mm and 20.6 at 135 of flexion. Interpretation: Reconstructing anterior cruciate ligament in total knee arthroplasty has been approved to be an more efficient way of maintaining normal knee kinematics comparing to posterior cruciate ligament retained and posterior cruciate ligament substituted total knee arthroplasty. PMID:27347334

ANTERIOR SUPERIOR DISLOCATION OF THE HIP JOINT: A ...

African Journals Online (AJOL)

Owing to the ligamentous and muscle forces around the hip, it is only rarely ... operating table, the femoral head was exposed via an anterior approach and found just below the sartorius muscle. The ligamentum teres was found avulsed, and the iliopubic .... of the socket tearing the iliofemoral ligament in the process, or ...

Failed anterior cruciate ligament reconstruction: analysis of factors leading to instability after primary surgery.

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Ma, Yong; Ao, Ying-Fang; Yu, Jia-Kuo; Dai, Ling-Hui; Shao, Zhen-Xing

2013-01-01

Revision anterior cruciate ligament (ACL) surgery can be expected to become more common as the number of primary reconstruction keeps increasing. This study aims to investigate the factors causing instability after primary ACL reconstruction, which may provide an essential scientific base to prevent surgical failure. One hundred and ten revision ACL surgeries were performed at our institute between November 2001 and July 2012. There were 74 men and 36 women, and the mean age at the time of revision was 27.6 years (range 16 - 56 years). The factors leading to instability after primary ACL reconstruction were retrospectively reviewed. Fifty-one knees failed because of bone tunnel malposition, with too anterior femoral tunnels (20 knees), posterior wall blowout (1 knee), vertical femoral tunnels (7 knees), too posterior tibial tunnels (12 knees), and too anterior tibial tunnels (10 knees). There was another knee performed with open surgery, where the femoral tunnel was drilled through the medial condyle and the tibial tunnel was too anterior. Five knees were found with malposition of the fixation. One knee with allograft was suspected of rejection and a second surgery had been made to take out the graft. Three knees met recurrent instability after postoperative infection. The other factors included traumatic (48 knees) and unidentified (12 knees). Technical errors were the main factors leading to instability after primary ACL reconstructions, while attention should also be paid to the risk factors of re-injury and failure of graft incorporation.

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

International Nuclear Information System (INIS)

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)

Transtrochanteric rotational osteotomy for avascular necrosis of the femoral head after unstable slipped capital femoral epiphysis: 10-year clinical results.

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Nakashima, Yasuharu; Yamamoto, Takuaki; Fukushi, Jun-Ichi; Motomura, Goro; Hamai, Satoshi; Kohno, Yusuke; Iwamoto, Yukihide

2016-11-01

Avascular necrosis of the femoral head (AVN) is the most serious complication after unstable slipped capital femoral epiphysis (SCFE), and is often unsalvageable. We report a minimum 10 years of clinical results for transtrochanteric rotational osteotomy of the femoral head (TRO) for AVN. This study included 7 patients (7 hips) with a mean age at surgery of 13.3 years, and the follow-up period was 15.8 years. All patients had prior treatment via closed reduction and pinning of the unstable SCFE, and showed severely collapsed femoral heads. The direction of rotation was anterior in 3 hips and posterior in 4. The Merle d'Aubigné-Postel score (MDPS) was used for clinical assessment, and joint degeneration was assessed with the Kellgren and Lawrence classification (KL-grade). The spherical intact area of the femoral head was moved to the weight-bearing portion, and subluxation was corrected via rotation combined with intentional varus positioning. The mean MDPS improved from 10.3 points to 15.6 points at 5 years, and it was maintained at 15.0 points by 10 years; 3 hips were excellent, 1 was good, 2 were fair, and 1 showed poor outcomes. No patient experienced re-collapse after TRO or required conversion to hip replacement or arthrodesis. After 10 years, degenerative changes became evident over time, and 2 hips progressed to KL-4 with a decreased MDPS. Although some joint degeneration is inevitable in the long-term, TRO is an effective salvage procedure for treating AVN after unstable SCFE. Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Femoral anteversion assessment: Comparison of physical examination, gait analysis, and EOS biplanar radiography.

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Westberry, David E; Wack, Linda I; Davis, Roy B; Hardin, James W

2018-05-01

Multiple measurement methods are available to assess transverse plane alignment of the lower extremity. This study was performed to determine the extent of correlation between femoral anteversion assessment using simultaneous biplanar radiographs and three-dimensional modeling (EOS imaging), clinical hip rotation by physical examination, and dynamic hip rotation assessed by gait analysis. Seventy-seven patients with cerebral palsy (GMFCS Level I and II) and 33 neurologically typical children with torsional abnormalities completed a comprehensive gait analysis with same day biplanar anterior-posterior and lateral radiographs and three-dimensional transverse plane assessment of femoral anteversion. Correlations were determined between physical exam of hip rotation, EOS imaging of femoral anteversion, and transverse plane hip kinematics for this retrospective review study. Linear regression analysis revealed a weak relationship between physical examination measures of hip rotation and biplanar radiographic assessment of femoral anteversion. Similarly, poor correlation was found between clinical evaluation of femoral anteversion and motion assessment of dynamic hip rotation. Correlations were better in neurologically typical children with torsional abnormalities compared to children with gait dysfunction secondary to cerebral palsy. Dynamic hip rotation cannot be predicted by physical examination measures of hip range of motion or from three-dimensional assessment of femoral anteversion derived from biplanar radiographs. Copyright © 2018 Elsevier B.V. All rights reserved.

Computational Modelling of Patella Femoral Kinematics During Gait Cycle and Experimental Validation

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Maiti, Raman

2016-06-01

The effect of loading and boundary conditions on patellar mechanics is significant due to the complications arising in patella femoral joints during total knee replacements. To understand the patellar mechanics with respect to loading and motion, a computational model representing the patella femoral joint was developed and validated against experimental results. The computational model was created in IDEAS NX and simulated in MSC ADAMS/VIEW software. The results obtained in the form of internal external rotations and anterior posterior displacements for a new and experimentally simulated specimen for patella femoral joint under standard gait condition were compared with experimental measurements performed on the Leeds ProSim knee simulator. A good overall agreement between the computational prediction and the experimental data was obtained for patella femoral kinematics. Good agreement between the model and the past studies was observed when the ligament load was removed and the medial lateral displacement was constrained. The model is sensitive to ±5 % change in kinematics, frictional, force and stiffness coefficients and insensitive to time step.

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

NARCIS (Netherlands)

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

Context-Dependent Functional Divergence of the Notch Ligands DLL1 and DLL4 In Vivo.

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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.

Innervation of the Anterior Sacroiliac Joint.

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Cox, Marcus; Ng, Garrett; Mashriqi, Faizullah; Iwanaga, Joe; Alonso, Fernando; Tubbs, Kevin; Loukas, Marios; Oskouian, Rod J; Tubbs, R Shane

2017-11-01

Sacroiliac joint pain can be disabling and recalcitrant to medical therapy. The innervation of this joint is poorly understood, especially its anterior aspect. Therefore, the present cadaveric study was performed to better elucidate this anatomy. Twenty-four cadaveric sides underwent dissection of the anterior sacroiliac joint, with special attention given to any branches from regional nerves to this joint. No femoral, obturator, or lumbosacral trunk branches destined to the anterior sacroiliac joint were identified in the 24 sides. In 20 sides, one or two small branches (less than 0.5 mm in diameter) were found to arise from the L4 ventral ramus (10%), the L5 ventral ramus (80%), or simultaneously from both the L4 and L5 ventral rami (10%). The length of the branches ranged from 5 to 31 mm (mean, 14 mm). All these branches arose from the posterior part of the nerves and traveled to the anterior surface of the sacroiliac joint. No statistical significance was found between sides or sexes. An improved knowledge of the innervation of the anterior sacroiliac joint might decrease suffering in patients with chronic sacroiliac joint pain. Copyright © 2017 Elsevier Inc. All rights reserved.

Notch sensitivity of aliphatic polyketone terpolymers

NARCIS (Netherlands)

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

The effect of anterior proton beams in the setting of a prostate-rectum spacer

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Christodouleas, John P., E-mail: christojo@uphs.upenn.edu [Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA (United States); Tang, Shikui [Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA (United States); Susil, Robert C.; McNutt, Todd R.; Song, Danny Y. [Department of Radiation Oncology and Radiation Molecular Sciences, Johns Hopkins Hospital, Baltimore, MD (United States); Bekelman, Justin; Deville, Curtiland; Vapiwala, Neha [Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA (United States); DeWeese, Theodore L. [Department of Radiation Oncology and Radiation Molecular Sciences, Johns Hopkins Hospital, Baltimore, MD (United States); Lu, Hsiao-Ming [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Both, Stefan [Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA (United States)

2013-10-01

Studies suggest that anterior beams with in vivo range verification would improve rectal dosimetry in proton therapy for prostate cancer. We investigated whether prostate-rectum spacers would enhance or diminish the benefits of anterior proton beams in these treatments. Twenty milliliters of hydrogel was injected between the prostate and rectum of a cadaver using a transperineal approach. Computed tomography (CT) and magnetic resonance (MR) images were used to generate 7 uniform scanning (US) and 7 single-field uniform dose pencil-beam scanning (PBS) plans with different beam arrangements. Pearson correlations were calculated between rectal, bladder, and femoral head dosimetric outcomes and beam arrangement anterior scores, which characterize the degree to which dose is delivered anteriorly. The overall quality of each plan was compared using a virtual dose-escalation study. For US plans, rectal mean dose was inversely correlated with anterior score, but for PBS plans there was no association between rectal mean dose and anterior score. For both US and PBS plans, full bladder and empty bladder mean doses were correlated with anterior scores. For both US and PBS plans, femoral head mean doses were inversely correlated with anterior score. For US plans and a full bladder, 4 beam arrangements that included an anterior beam tied for the highest maximum prescription dose (MPD). For US plans and an empty bladder, the arrangement with 1 anterior and 2 anterior oblique beams achieved the highest MPD in the virtual dose-escalation study. The dose-escalation study did not differentiate beam arrangements for PBS. All arrangements in the dose-escalation study were limited by bladder constraints except for the arrangement with 2 posterior oblique beams. The benefits of anterior proton beams in the setting of prostate-rectum spacers appear to be proton modality dependent and may not extend to PBS.

The effect of anterior proton beams in the setting of a prostate-rectum spacer

Science.gov (United States)

Christodouleas, John P.; Tang, Shikui; Susil, Robert C.; McNutt, Todd R.; Song, Danny Y.; Bekelman, Justin; Deville, Curtiland; Vapiwala, Neha; DeWeese, Theodore L.; Lu, Hsiao-Ming; Both, Stefan

2014-01-01

Studies suggest that anterior beams with in vivo range verification would improve rectal dosimetry in proton therapy for prostate cancer. We investigated whether prostate-rectum spacers would enhance or diminish the benefits of anterior proton beams in these treatments. Twenty milliliters of hydrogel was injected between the prostate and rectum of a cadaver using a transperineal approach. Computed tomography (CT) and magnetic resonance (MR) images were used to generate 7 uniform scanning (US) and 7 single-field uniform dose pencil-beam scanning (PBS) plans with different beam arrangements. Pearson correlations were calculated between rectal, bladder, and femoral head dosimetric outcomes and beam arrangement anterior scores, which characterize the degree to which dose is delivered anteriorly. The overall quality of each plan was compared using a virtual dose-escalation study. For US plans, rectal mean dose was inversely correlated with anterior score, but for PBS plans there was no association between rectal mean dose and anterior score. For both US and PBS plans, full bladder and empty bladder mean doses were correlated with anterior scores. For both US and PBS plans, femoral head mean doses were inversely correlated with anterior score. For US plans and a full bladder, 4 beam arrangements that included an anterior beam tied for the highest maximum prescription dose (MPD). For US plans and an empty bladder, the arrangement with 1 anterior and 2 anterior oblique beams achieved the highest MPD in the virtual dose-escalation study. The dose-escalation study did not differentiate beam arrangements for PBS. All arrangements in the dose-escalation study were limited by bladder constraints except for the arrangement with 2 posterior oblique beams. The benefits of anterior proton beams in the setting of prostate-rectum spacers appear to be proton modality dependent and may not extend to PBS. PMID:23578497

Results of triple muscle (sartorius, tensor fascia latae and part of gluteus medius pedicle bone grafting in neglected femoral neck fracture in physiologically active patients

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Pankaj Kumar Mishra

2014-01-01

Full Text Available Background: Femoral neck fractures are notorious for complications like avascular necrosis and nonunion. In developing countries, various factors such as illiteracy, low socioeconomic status, ignorance are responsible for the delay in surgery. Neglected fracture neck femur always poses a formidable challenge. The purpose of this study was to evaluate the results of triple muscle pedicle bone grafting using sartorius, tensor fasciae latae and part of gluteus medius in neglected femoral neck fracture. Materials and Methods: This is a retrospective study with medical record of 50 patients, who were operated by open reduction, internal fixation along with muscle pedicle bone grafting by the anterior approach. After open reduction, two to three cancellous screws (6.5 mm were used for internal fixation in all cases. A bony chunk of the whole anterior superior iliac spine of 1 cm thickness, 1 cm width and 4.5 cm length, taken from the iliac crest comprised of muscle pedicle of sartorius, tensor fascia latae and part of gluteus medius. Then the graft with all three muscles mobilized and put in the trough made over the anterior or anterosuperior aspect of the femoral head. The graft was fixed with one or two 4.5 mm self-tapping cortical screw in anterior to posterior direction. Results: 14 patients were lost to followup. The results were based on 36 patients. We observed that in our series, there was union in 34, out of 36 (94.4% patients. All patients were within the age group of 15-51 years (average 38 years with displaced neglected femoral neck fracture of ≥30 days. Mean time taken for full clinicoradiological union was 14 weeks (range-10-24 weeks. Conclusion: Triple muscle pedicle bone grafting gives satisfactory results for neglected femoral neck fracture in physiologically active patients.

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

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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.

Band-notched spiral antenna

Science.gov (United States)

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.

Drilling the femoral tunnel during ACL reconstruction: transtibial versus anteromedial portal techniques.

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Tudisco, Cosimo; Bisicchia, Salvatore

2012-08-01

Incorrect bone tunnel position, particularly on the femoral side, is a frequent cause of failed anterior cruciate ligament reconstruction. Several studies have reported that drilling the femoral tunnel through the anteromedial portal allows a more anatomical placement on the lateral femoral condyle and higher knee stability than does transtibial reconstruction.In the current study, the femoral tunnel was drilled with transtibial (n=6) and anteromedial (n=6) portal techniques in 12 cadaveric knees. With appropriate landmarks inserted into bone tunnels, the direction and length of the tunnels were determined on anteroposterior and lateral radiographs. Knee stability was evaluated with a KT1000 arthrometer (MEDmetric Corporation, San Diego, California) and pivot shift test, comparing the pre- and postoperative values of both techniques. Finally, all knees were dissected to enhance vision of the insertion of the reconstructed ligament. The anteromedial portal technique led to better placement of the femoral tunnel in the coronal and sagittal planes, with higher knee stability according to the pivot shift test but not the KT1000 arthrometer. Anatomical and clinical results reported in the literature on transtibial and anteromedial portal techniques are controversial, but most of studies report better results with the anteromedial portal technique, especially regarding rotational stability. The current cadaveric study showed that the anteromedial portal technique provided better tunnel placement on the lateral femoral condyle in the coronal and sagittal planes, with an improvement in the rotational stability of the knee. Copyright 2012, SLACK Incorporated.

A anatomic evaluation of the lateral femoral circumflex artery system by using Multi detector-row CT

International Nuclear Information System (INIS)

Haraguchi, Kazunari; Kadota, Satoshi; Hosaka, Yoshiaki

2010-01-01

Flaps that are pedicled by perforators of the lateral femoral circumflex artery (LFCA) system have many advantages, including the transplantation of large and reliable skin with long pedicles and a large diameter, and little invasion of the donor sites. However, preoperative planning has been difficult because the perforators have many anatomic variations. We used multi detector-row CT for anatomical evaluation of the lateral femoral circumflex artery system. The patterns of LFCA from the main vessels were classified into three types and vessels coursing toward the lateral thigh region were classified into three groups. The distance from the anterior superior iliac spine to the lateral femoral circumflex artery showed no significant difference between men and women. We were able to evaluate vessels with a 2-mm diameter in the lateral femoral circumflex artery system, indicating that accurate evaluation and low invasive examination of the lateral femoral circumflex artery system, including the perforator area, can be achieved by adjusting the image conditions and the injection rate of the contrast dye. (author)

Effectiveness of the magnetic resonance imaging for the therapy of avascular necrosis of the femoral head

International Nuclear Information System (INIS)

Oda, Yoshinao; Katsuki, Ichirou; Ushijima, Masahiro; Tsutsui, Hideki; Sugioka, Youichi

1990-01-01

Recently, some reports demonstrate the usefulness of the magnetic resonance imaging (MRI) for early diagnosis of the avascular necrosis of the femoral head (ANF). In this report we analyzed 64 hips in 40 cases using preoperative plain radiographs, tomography and MRI affected by ANF. And we gained following three conclusions. When rotational osteotomy of the femoral head is to be carried out, two plain views of MRI, parallel and contrary to the axis of the femoral neck, were useful for evaluation of postoperative weight bearing area. In 58 hips with strinct the former two plain views of MRI, atrophy of posterior area of the femoral head was recognized in 54 hips by tomography, and of them abnormal signal in posterior was revealed in 32 hips by MRI. In 28 hips performed anterior rotational osteotomy, atrophy of posterior area of the femoral head was recognized in 26 hips by tomography, and of them abnormal signal in posterior was revealed in 6 hips by MRI. In such cases careful follow-up should be required. (author)

Effectiveness of the magnetic resonance imaging for the therapy of avascular necrosis of the femoral head

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Oda, Yoshinao; Katsuki, Ichirou; Ushijima, Masahiro; Tsutsui, Hideki; Sugioka, Youichi [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

1990-03-01

Recently, some reports demonstrate the usefulness of the magnetic resonance imaging (MRI) for early diagnosis of the avascular necrosis of the femoral head (ANF). In this report we analyzed 64 hips in 40 cases using preoperative plain radiographs, tomography and MRI affected by ANF. And we gained following three conclusions. When rotational osteotomy of the femoral head is to be carried out, two plain views of MRI, parallel and contrary to the axis of the femoral neck, were useful for evaluation of postoperative weight bearing area. In 58 hips with strinct the former two plain views of MRI, atrophy of posterior area of the femoral head was recognized in 54 hips by tomography, and of them abnormal signal in posterior was revealed in 32 hips by MRI. In 28 hips performed anterior rotational osteotomy, atrophy of posterior area of the femoral head was recognized in 26 hips by tomography, and of them abnormal signal in posterior was revealed in 6 hips by MRI. In such cases careful follow-up should be required. (author).

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

Science.gov (United States)

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

Quantitative Comparison of the Microscopic Anatomy of the Human ACL Femoral and Tibial Entheses

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Beaulieu, Mélanie L.; Carey, Grace E.; Schlecht, Stephen H.; Wojtys, Edward M.; Ashton-Miller, James A.

2015-01-01

The femoral enthesis of the human anterior cruciate ligament (ACL) is known to be more susceptible to injury than the tibial enthesis. To determine whether anatomic differences might help explain this difference, we quantified the microscopic appearance of both entheses in 15 unembalmed knee specimens using light microscopy, toluidine blue stain and image analysis. The amount of calcified fibrocartilage and uncalcified fibrocartilage, and the ligament entheseal attachment angle were then compared between the femoral and tibial entheses via linear mixed-effects models. The results showed marked differences in anatomy between the two entheses. The femoral enthesis exhibited a 3.9-fold more acute ligament attachment angle than the tibial enthesis (p fibrocartilage tissue area (p fibrocartilage depth (p fibrocartilage and a more acute ligament attachment angle than the tibial enthesis, which provides insight into why it is more vulnerable to failure. PMID:26134706

Alterations in Notch signalling in skeletal muscles from mdx and dko dystrophic mice and patients with Duchenne muscular dystrophy.

Science.gov (United States)

Church, Jarrod E; Trieu, Jennifer; Chee, Annabel; Naim, Timur; Gehrig, Stefan M; Lamon, Séverine; Angelini, Corrado; Russell, Aaron P; Lynch, Gordon S

2014-04-01

New Findings What is the central question of this study? The Notch signalling pathway plays an important role in muscle regeneration, and activation of the pathway has been shown to enhance muscle regeneration in aged mice. It is unknown whether Notch activation will have a similarly beneficial effect on muscle regeneration in the context of Duchenne muscular dystrophy (DMD). What is the main finding and its importance? Although expression of Notch signalling components is altered in both mouse models of DMD and in human DMD patients, activation of the Notch signalling pathway does not confer any functional benefit on muscles from dystrophic mice, suggesting that other signalling pathways may be more fruitful targets for manipulation in treating DMD. Abstract In Duchenne muscular dystrophy (DMD), muscle damage and impaired regeneration lead to progressive muscle wasting, weakness and premature death. The Notch signalling pathway represents a central regulator of gene expression and is critical for cellular proliferation, differentiation and apoptotic signalling during all stages of embryonic muscle development. Notch activation improves muscle regeneration in aged mice, but its potential to restore regeneration and function in muscular dystrophy is unknown. We performed a comprehensive examination of several genes involved in Notch signalling in muscles from dystrophin-deficient mdx and dko (utrophin- and dystrophin-null) mice and DMD patients. A reduction of Notch1 and Hes1 mRNA in tibialis anterior muscles of dko mice and quadriceps muscles of DMD patients and a reduction of Hes1 mRNA in the diaphragm of the mdx mice were observed, with other targets being inconsistent across species. Activation and inhibition of Notch signalling, followed by measures of muscle regeneration and function, were performed in the mouse models of DMD. Notch activation had no effect on functional regeneration in C57BL/10, mdx or dko mice. Notch inhibition significantly depressed the

Notch Inhibits Osteoblast Differentiation and Causes Osteopenia

Science.gov (United States)

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

Comparison of the effectiveness of femoral fixation techniques (Aperfix and Endobutton in anterior cruciate ligament surgery: A clinical trial in men with complete anterior cruciate ligament rupture

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Seyyed Raza Sharifzadeh

2017-09-01

Full Text Available Background Anterior cruciate ligament (ACL is a Strengthener ligament of the knee. About 50 persons per 100,000 annually counter ACL rupture. Based on studies, the majority of people who have high mobility jobs, and had reconstruction surgery after ACL rupture, have returned to pre-injury level of activity. Aims We compared two methods of surgery (aperfix and endobutton in this article. We want to answer these two main questions in this study:1 is the effectiveness of surgical methods (aperfix and endobutton in patients with anterior cruciate ligament rupture, the same?.2 Are the aspects of the knee function, in two surgical methods (aperfix and endobutton after ACL reconstruction surgery, the same? Methods This study is a prospective clinical trial on patients who had complete ACL rupture in an isolated trauma, who were nominated for ACL reconstruction surgery. We excluded the cases that had underlying disease or other damages from the study. 100 patients were randomly divided into two groups of 50 individuals. Then each group underwent surgery. The femoral fixations were by the two common methods of ";;;;;;;;;;;Aperfix";;;;;;;;;;; or ";;;;;;;;;;;Endobutton";;;;;;;;;;;. We followed up, the cases one year after surgery and evaluated them by lysholm score as well as with IKDC score. Results The mean lysholm score and IKDC score do not have statistically significant difference in the two groups. (Mean lysholm score in Aperfix group=95.66 vs. 94.56 in Endobutton group (p=0.057 and IKDC score=92.32 in Aperfix group vs 92.20 in Endobutton group (p=0.28. However, in some aspects of knee function, such as locking, Swelling, and climbing stairs, patients who had undergone Aperfix approach, had better results. Conclusion Surgical methods have little difference however due to better results in some aspects of knee functions in this study and due to other studies, it can be said Aperfix method slightly has more benefits. Further investigations with larger

ediatric femoral shaft fractures treated by flexible intramedullary nailing.

Science.gov (United States)

Kapil Mani, K C; Dirgha Raj, R C; Parimal, Acharya

2015-01-01

Nowadays pediatric femoral fractures are more commonly managed with operative treatment rather than conservative treatment because of more rapid recovery and avoidance of prolonged immobilization. Children between the ages of 5-13 years are treated either by traction plus hip spica and flexible/elastic stable retrograde intramedullary nail, or external fixators in the case of open fractures. The aim of this study is to evaluate the outcome of pediatric femoral shaft fractures treated by stainless steel flexible intramedullary nail in children between 5 and 13 years of age. There were 32 cases of femoral shaft fractures which were all fixed with stainless steel flexible intramedullary nail under fluoroscopy. Long leg cast was applied at the time of fixation. Partial weight bearing was started 2 weeks after surgery. Patients were evaluated in follow-up study to observe the alignment of fracture, infection, delayed union, nonunion, limb length discrepancy, motion of knee joint, and time to unite the fracture. We were able to follow up 28 out of 32 patients. The patients were 8.14 years of age on average. The mean hospital stay after operation was 4 days and fracture union time was 9.57 weeks. There were 3 cases of varus angulation, 2 cases of anterior angulation, and 4 cases of limb lengthening. Patients aged between 5 and 13 years treated with flexible intramedullary nail for closed femoral shaft fracture have rapid union and recovery, short rehabilitation period, less immobilization and psychological impact, and cost-effective.

Notch-strengthening in two-dimensional foams

NARCIS (Netherlands)

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

Common site of subchondral insufficiency fractures of the femoral head based on three-dimensional magnetic resonance imaging

Energy Technology Data Exchange (ETDEWEB)

Iwasaki, Kenyu; Yamamoto, Takuaki; Motomura, Goro; Karasuyama, Kazuyuki; Sonoda, Kazuhiko; Kubo, Yusuke; Iwamoto, Yukihide [Kyushu University, Department of Orthopaedic Surgery Graduate School of Medical Sciences, Higashi-ku, Fukuoka (Japan)

2016-01-15

The objective of this study was to investigate the common sites of subchondral insufficiency fractures of the femoral head (SIF) based on three-dimensional (3-D) reconstruction of MR images. In 33 hips of 31 consecutive patients diagnosed with SIF, 3-D reconstruction of the bone, fracture, and acetabular edge was performed using MR images. These 3-D images were used to measure the fractured areas and clarify the positional relationship between the fracture and degree of acetabular coverage. The fractured area in the anterior portion was significantly larger than in the posterior area. In 11 cases, the fractures contacted the acetabular edge and were distributed on the lateral portion. The indices of acetabular coverage (center-edge angle and acetabular head index) in these cases were less than the normal range. In the remaining 22 cases, the fractures were apart from the acetabular edge and distributed on the mediolateral centerline of the femoral head. The majority of these cases had normal acetabular coverage. The common site of SIF is the anterior portion. In addition, two types of SIF are proposed: (1) Lateral type: the contact stress between the acetabular edge and lateral portion of the femoral head causes SIF based on the insufficient acetabular coverage, and (2) Central type: the contact stress between the acetabular surface and the mediolateral center of the femoral head causes SIF independent from the insufficiency of acetabular coverage. These findings may be useful for considering the treatment and prevention of SIF. (orig.)

The "suprasellar notch," or the tuberculum sellae as seen from below: definition, features, and clinical implications from an endoscopic endonasal perspective.

Science.gov (United States)

de Notaris, Matteo; Solari, Domenico; Cavallo, Luigi M; D'Enza, Alfonso Iodice; Enseñat, Joaquim; Berenguer, Joan; Ferrer, Enrique; Prats-Galino, Alberto; Cappabianca, Paolo

2012-03-01

The tuberculum sellae is a bony elevation ridge that lines up the anterior aspect of the sella, dividing it from the chiasmatic groove. The recent use of the endoscopic endonasal transtuberculum approach has provided surgeons with a method to reach the suprasellar area, offering a new surgical point of view somehow "opposite" of this area. The authors of this study aimed to define the tuberculum sellae as seen from the endoscopic endonasal view while also providing CT-based systematic measurements to objectively detail the anatomical features of such a structure, which was renamed the "suprasellar notch." The authors analyzed routine skull CT scans from 24 patients with no brain pathology or fractures and measured the interoptic distance at the level of the limbus sphenoidale, the chiasmatic groove sulcal length and width, and the angle of the suprasellar notch. Indeed, the suprasellar notch was defined as the angle between 2 lines, the first passing through the tuberculum sellae midpoint and perpendicular to the cribriform plate, and a second line passing between 2 points, the midpoints of the limbus sphenoidale and the tuberculum sellae. Moreover, the authors performed on 15 cadaveric heads an endoscopic endonasal transplanum transtuberculum approach with the aid of a neuronavigator to achieve a step-by-step comparison with the radiological data. The whole CT scanning set was statistically analyzed to determine the statistical interdependency of the suprasellar notch angle with the other 3 measurements, that is, the sulcal length at the midline, the interoptic distance at the optic canal entrance, and the interoptic distance at the limbus. Based on the endoscopic endonasal view and CT imaging analysis, the authors identified a certain anatomical variability and thus introduced a new classification of the suprasellar notch: Type I, angle 138°. They then analyzed the surgical implications of the endoscopic endonasal approach to the suprasellar area, which could be

Strategies for revision surgery after primary double-bundle anterior cruciate ligament (ACL) reconstruction

NARCIS (Netherlands)

Hofbauer, Marcus; Muller, Bart; Murawski, Christopher D.; Baraga, Michael; van Eck, Carola Franziska; Fu, Freddie H.

2013-01-01

The purpose of this article was to discuss pre- and intra-operative considerations as well as surgical strategies for different femoral and tibial tunnel scenarios in revision surgery following primary double-bundle anterior cruciate ligament (ACL) reconstruction. Based on the current literature of

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

NARCIS (Netherlands)

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

Notch filters for port-Hamiltonian systems

NARCIS (Netherlands)

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

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

International Nuclear Information System (INIS)

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

Three-Dimensional Analysis of the Curvature of the Femoral Canal in 426 Chinese Femurs

Directory of Open Access Journals (Sweden)

Xiu-Yun Su

2015-01-01

Full Text Available Purpose. The human femur has long been considered to have an anatomical anterior curvature in the sagittal plane. We established a new method to evaluate the femoral curvature in three-dimensional (3D space and reveal its influencing factors in Chinese population. Methods. 3D models of 426 femurs and the medullary canal were constructed using Mimics software. We standardized the positions of all femurs using 3ds Max software. After measuring the anatomical parameters, including the radius of femoral curvature (RFC and banking angle, of the femurs using the established femur-specific coordinate system, we analyzed and determined the relationships between the anatomical parameters of the femur and the general characteristics of the population. Results. Pearson’s correlation analyses showed that there were positive correlations between the RFC and height (r=0.339, p<0.001 and the femoral length and RFC (r=0.369, p<0.001 and a negative correlation between the femoral length and banking angle (r=-0.223, p<0.001. Stepwise linear regression analyses showed that the most relevant factors for the RFC and banking angle were the femoral length and gender, respectively. Conclusions. This study concluded that the banking angle of the femur was significantly larger in female than in male.

Eddy current standards - Cracks versus notches

Science.gov (United States)

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.

Geometric Characteristics of the Knee Are Associated With a Noncontact ACL Injury to the Contralateral Knee After Unilateral ACL Injury in Young Female Athletes.

Science.gov (United States)

Levins, James G; Argentieri, Erin C; Sturnick, Daniel R; Gardner-Morse, Mack; Vacek, Pamela M; Tourville, Timothy W; Johnson, Robert J; Slauterbeck, James R; Beynnon, Bruce D

2017-12-01

Contralateral anterior cruciate ligament (CACL) injury after recovery from a first-time ACL rupture occurs at a high rate in young females; however, little is known about the risk factors associated with bilateral ACL trauma. The geometric characteristics of the contralateral knee at the time of the initial ACL injury are associated with risk of suffering a CACL injury in these female athletes. Case-control study; Level of evidence, 3. Sixty-two female athletes who suffered their first noncontact ACL injury while participating in sports at the high school or college level were identified, and geometry of the femoral notch, ACL, tibial spines, tibial subchondral bone, articular cartilage surfaces, and menisci of the contralateral, uninjured, knee was characterized in 3 dimensions. We were unable to contact 7 subjects and followed the remaining 55 until either a CACL injury or an ACL graft injury occurred or, if they were not injured, until the date of last contact (mean, 34 months after their first ACL injury). Cox regression was used to identify risk factors for CACL injury. Ten (18.2%) females suffered a CACL injury. Decreases of 1 SD in femoral intercondylar notch width (measured at its outlet and anterior attachment of the ACL) were associated with increases in the risk of suffering a CACL injury (hazard ratio = 1.88 and 2.05, respectively). Likewise, 1 SD decreases in medial-lateral width of the lateral tibial spine, height of the medial tibial spine, and thickness of the articular cartilage located at the posterior region of the medial tibial compartment were associated with 3.59-, 1.75-, and 2.15-fold increases in the risk of CACL injury, respectively. After ACL injury, subsequent injury to the CACL is influenced by geometry of the structures that surround the ACL (the femoral notch and tibial spines). This information can be used to identify individuals at increased risk for CACL trauma, who might benefit from targeted risk-reduction interventions.

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

Science.gov (United States)

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.

Subchondral bone density distribution in the human femoral head

Energy Technology Data Exchange (ETDEWEB)

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.)

Radiographic femoral varus measurement is affected unpredictably by femoral rotation

DEFF Research Database (Denmark)

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...

DOL behaviour of end-notched beams

DEFF Research Database (Denmark)

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...

Complications Using Bioabsorbable Cross-Pin Femoral Fixation: A Case Report and Review of the Literature

Directory of Open Access Journals (Sweden)

Saqib Hasan

2011-01-01

Full Text Available The use of bioabsorbable cross-pin transcondylar fixation has remained a viable option for femoral fixation in anterior cruciate ligament reconstruction. Although numerous biomechanical studies have demonstrated high fixation strength and minimal slippage with use of this method of fixation, there have been increasing reports of a variety of clinical complications associated with these implants. We reviewed the literature for all complications associated with the Bio-TransFix implant and present a case report of a patient status after ACL reconstruction using Bio-TransFix cross-pin femoral fixation with iliotibial band friction syndrome from a broken cross-pin four month post-operatively.

Biochemical characterization and cellular effects of CADASIL mutants of NOTCH3.

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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.

Analysis list: NOTCH1 [Chip-atlas[Archive

Lifescience Database Archive (English)

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 ...

A semi-automatic method for positioning a femoral bone reconstruction for strict view generation.

Science.gov (United States)

Milano, Federico; Ritacco, Lucas; Gomez, Adrian; Gonzalez Bernaldo de Quiros, Fernan; Risk, Marcelo

2010-01-01

In this paper we present a semi-automatic method for femoral bone positioning after 3D image reconstruction from Computed Tomography images. This serves as grounding for the definition of strict axial, longitudinal and anterior-posterior views, overcoming the problem of patient positioning biases in 2D femoral bone measuring methods. After the bone reconstruction is aligned to a standard reference frame, new tomographic slices can be generated, on which unbiased measures may be taken. This could allow not only accurate inter-patient comparisons but also intra-patient comparisons, i.e., comparisons of images of the same patient taken at different times. This method could enable medical doctors to diagnose and follow up several bone deformities more easily.

A case report of a completely displaced stress fracture of the femoral shaft in a middle-aged male athlete - A precursor of things to come?

Science.gov (United States)

Larsen, Peter; Elsoe, Rasmus; Rathleff, Michael S

2016-05-01

Displaced stress fractures of the femoral shaft are very uncommon. The proportion of middle-aged and older age groups participating in long-distance running, triathlon and other high intensity sports is increasing. As a consequence stress fracture of the femoral shaft may be on the rise in the future. The patient was 43 years old male caucasian triathlete. The authors met the patient after he was admitted with a displaced femoral shaft fracture. The fracture occurred during running at the national championship in ½ Ironman. The patient reported that his symptoms had gradually developed over the last month before the fracture with pain localized anterior to the thigh. The patient interpreted the symptoms as local muscle damage. A clinical examination was conducted by a physiotherapist and the symptoms were interpreted as a simple muscle injury in the quadriceps. When presented with a patient with non-traumatic, diffuse anterior thigh pain in an individual of this age, who is participating in high-level endurance running; clinicians should consider the possibility that the cause of the symptoms may be a femoral shaft stress fracture. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quantitative comparison of the microscopic anatomy of the human ACL femoral and tibial entheses.

Science.gov (United States)

Beaulieu, Mélanie L; Carey, Grace E; Schlecht, Stephen H; Wojtys, Edward M; Ashton-Miller, James A

2015-12-01

The femoral enthesis of the human anterior cruciate ligament (ACL) is known to be more susceptible to injury than the tibial enthesis. To determine whether anatomic differences might help explain this difference, we quantified the microscopic appearance of both entheses in 15 unembalmed knee specimens using light microscopy, toluidine blue stain and image analysis. The amount of calcified fibrocartilage and uncalcified fibrocartilage, and the ligament entheseal attachment angle were then compared between the femoral and tibial entheses via linear mixed-effects models. The results showed marked differences in anatomy between the two entheses. The femoral enthesis exhibited a 3.9-fold more acute ligament attachment angle than the tibial enthesis (p<0.001), a 43% greater calcified fibrocartilage tissue area (p<0.001), and a 226% greater uncalcified fibrocartilage depth (p<0.001), with the latter differences being particularly pronounced in the central region. We conclude that the ACL femoral enthesis has more fibrocartilage and a more acute ligament attachment angle than the tibial enthesis, which provides insight into why it is more vulnerable to failure. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

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

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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

Notch Signaling: Piercing a Harness of Simplicity

NARCIS (Netherlands)

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

Notch3 signalling promotes tumour growth in colorectal cancer.

Science.gov (United States)

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.

Immediate postoperative anterior knee stability: double- versus triple-bundle anterior cruciate ligament reconstructions.

Science.gov (United States)

Mae, Tatsuo; Shino, Konsei; Matsumoto, Norinao; Yoneda, Kenji; Yoshikawa, Hideki; Nakata, Ken

2013-02-01

The purpose of this study was to compare the triple-bundle (TB) anterior cruciate ligament (ACL) reconstruction with the double-bundle (DB) ACL reconstruction in immediate postoperative anterior knee stability. This study involved 133 patients who had undergone the anatomic ACL reconstruction with autogenous hamstring tendon unilaterally. Then 83 patients (mean age, 28.8 years) underwent the DB between November 2004 and December 2005, and 50 patients (mean age, 29.6 years) underwent the TB ACL reconstruction between January and December 2006. The 2 femoral tunnels were created in the ideal ACL attachment area, whereas 2 tibial tunnels for the DB and 3 tunnels for the TB were created in the ACL footprint. The 2 doubled tendon grafts were fixed with EndoButton-CL (Smith & Nephew Endoscopy, Andover, MA) on the femur. The grafts were fixed to the tibia using a Double Spike Plate and a screw under the total initial tension of 20 N at 20° of flexion, after meticulous in situ pretensioning using a tensioning boot. Then immediate postoperative anterior knee laxity in response to 89 N of anterior load was measured by one experienced examiner (T.M.) with the KT-2000 Knee Arthrometer (MEDmedtric, San Diego, CA) under general anesthesia at 30° of knee flexion with muscle relaxants. The measured anterior laxity was 3.4 ± 1.2 mm in the DB and 2.5 ± 0.7 mm in the TB ACL reconstruction, a statistically significant difference. The side-to-side difference of the laxity was -3.2 ± 1.6 mm in the DB and -4.2 ± 2.0 mm in the TB, again a significant difference. TB ACL reconstruction resulted in better immediate postoperative anterior knee stability than DB ACL reconstruction under 89 N of anterior tibial load (P = .031). Level III, therapeutic retrospective comparative study. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Femoral Neck Strain during Maximal Contraction of Isolated Hip-Spanning Muscle Groups

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Saulo Martelli

2017-01-01

Full Text Available The aim of the study was to investigate femoral neck strain during maximal isometric contraction of the hip-spanning muscles. The musculoskeletal and the femur finite-element models from an elderly white woman were taken from earlier studies. The hip-spanning muscles were grouped by function in six hip-spanning muscle groups. The peak hip and knee moments in the model were matched to corresponding published measurements of the hip and knee moments during maximal isometric exercises about the hip and the knee in elderly participants. The femoral neck strain was calculated using full activation of the agonist muscles at fourteen physiological joint angles. The 5%±0.8% of the femoral neck volume exceeded the 90th percentile of the strain distribution across the 84 studied scenarios. Hip extensors, flexors, and abductors generated the highest tension in the proximal neck (2727 με, tension (986 με and compression (−2818 με in the anterior and posterior neck, and compression (−2069 με in the distal neck, respectively. Hip extensors and flexors generated the highest neck strain per unit of joint moment (63–67 με·m·N−1 at extreme hip angles. Therefore, femoral neck strain is heterogeneous and muscle contraction and posture dependent.

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

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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.

Progress Report on Alloy 617 Notched Specimen Testing

Energy Technology Data Exchange (ETDEWEB)

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.

Notch signaling and progenitor/ductular reaction in steatohepatitis.

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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.

Role of Notch signaling in the mammalian heart

Energy Technology Data Exchange (ETDEWEB)

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.

Double incision iso-anatomical ACL reconstruction: the freedom to place the femoral tunnel within the anatomical attachment site without exception.

Science.gov (United States)

Arnold, Markus P; Duthon, Victoria; Neyret, Philippe; Hirschmann, Michael T

2013-02-01

The present paper describes the rationale behind the surgical technique and the clinical results of the iso-anatomical, single bundle bone patellar-tendon bone anterior cruciate ligament (ACL) reconstruction. Using a second incision on the distal lateral femur an outside-in femoral tunnel is drilled. Guided by a special aiming device it is possible to place the femoral tunnel in the centre of the ACL footprint in every single case. Since every crucial step of the procedure is under visual control, the technique is safe and reliable, which is mirrored by good clinical results.

Common nonmutational NOTCH1 activation in chronic lymphocytic leukemia.

Science.gov (United States)

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.

Essential Role of Endothelial Notch1 in Angiogenesis

Science.gov (United States)

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

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

International Nuclear Information System (INIS)

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

Notch effects in uniaxial tension specimens

International Nuclear Information System (INIS)

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

Contact area between femoral tunnel and interference screw in anatomic rectangular tunnel ACL reconstruction: a comparison of outside-in and trans-portal inside-out techniques.

Science.gov (United States)

Hiramatsu, Kunihiko; Mae, Tatsuo; Tachibana, Yuta; Nakagawa, Shigeto; Shino, Konsei

2018-02-01

The purpose of this study was to compare the femoral tunnel length, the femoral graft bending angle at the femoral tunnel aperture, and the contact area between the femoral tunnel wall and an interference screw used for fixation in anatomic rectangular tunnel anterior cruciate ligament (ACL) reconstruction (ART ACLR). The study included 149 patients with primary ACL injury who underwent ART ACLR. Preoperatively, flexion angle of the index knee was checked under general anaesthesia. Those of less than 130° of passive flexion were assigned to the outside-in (OI) technique (78 patients), while the others to the trans-portal inside-out (TP) technique (71 patients). The patients underwent computed tomography with multiplanar reconstruction at 3-5 weeks post-operatively. Femoral tunnel length, graft bending angle, and contact ratio between the IFS and femoral tunnel were assessed. P contact ratio in the OI technique was significantly larger than that in the TP technique at every point in the femoral tunnel (P contact ratio than the TP technique after ART ACLR. Retrospective comparative study, Level III.

MR imaging features of chronically torn anterior cruciate ligament

International Nuclear Information System (INIS)

Niitsu, Mamoru; Kuramochi, Masashi; Ikeda, Kotaroh; Fukubayashi, Tohru; Anno, Izumi; Itai, Yuji

1995-01-01

Magnetic resonance (MR) images of 40 knee joints with arthroscopically proved chronic anterior cruciate ligament (ACL) tears were retrospectively evaluated. MRI demonstrated various features of chronic ACL tears: 19 knees revealed with no identifiable ligamentous structure, and 21 had residual ligamentous structures. These pseudoligaments, 14 discontinuous bands and seven continuous bands with elongation, were residual torn ligamentous fibers and/or synovial tissues. All the discontinuous bands were disrupted from the femoral attachment and were likely to traverse the lower intercondylar space. Six disrupted ligaments were attached to the lateral aspect of the posterior cruciate ligament (PCL). Coronal T2 * -weighted gradient echo images showed better delineation of the disrupted femoral attachment and adhesion to the PCL. A chronic ACL tear with minimal elongation or with PCL attachment at a higher position may occasionally be difficult to distinguish from an intact ligament. (author)

Stress concentration at notches

CERN Document Server

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 ...

Transportal femoral drilling creates more horizontal ACL graft orientation compared to transtibial drilling: A 3D CT imaging study.

Science.gov (United States)

Clockaerts, S; Van Haver, A; Verhaegen, J; Vuylsteke, K; Leenders, T; Lagae, K C; Verdonk, P

2016-06-01

The principle of anatomic anterior cruciate ligament (ACL) reconstruction is to create a femoral and tibial tunnel that resembles the insertion of the native ACL. Anatomic reconstruction leads to a more horizontal graft orientation that provides more rotational stability. The aim of this study is to investigate the best method to achieve anatomical reconstruction of femoral insertion of the ACL and thus, a more horizontal orientation of the ACL. We compared tunnel position and orientation between transportal femoral drilling technique and transtibial technique. Thirty-two patients were included. Post-operative CT scans were obtained and femur, tibia and ACL tunnels were reconstructed. The position and orientation of tibial and femoral tunnels were quantified using the quadrant method, and femoral tunnel length, ellipticity and posterior wall breakage were assessed. We also investigated clinical outcome. Analyses show that transportal drilled femoral tunnels were situated significantly lower than transtibial drilled tunnels (p<0.0001), resulting in a significantly more horizontal oriented ACL in the transportal group in coronal (p<0.0001) and sagittal plane (p=0.01). No differences were observed in depth of femoral tunnel position (p=0.44). Femoral tunnel length was shorter in the transportal group (p=0.01) with a more ellipsoidal femoral aperture (p=0.01). There were no differences between both groups in tibial position. There were no differences in clinical outcome measure between the transportal and transtibial groups. This study indicates that transportal drilling of the femoral tunnel leads to a more horizontal graft orientation of the ACL, without differences in clinical outcome. Copyright © 2016 Elsevier B.V. All rights reserved.

Femoral nerve damage (image)

Science.gov (United States)

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 ...

Femoral rotation unpredictably affects radiographic anatomical lateral distal femoral angle measurements

DEFF Research Database (Denmark)

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...

Minimally invasive anterior pelvic internal fixation: An anatomic study comparing Pelvic Bridge to INFIX.

Science.gov (United States)

Reichel, Lee M; MacCormick, Lauren M; Dugarte, Anthony J; Rizkala, Amir R; Graves, Sara C; Cole, Peter A

2018-02-01

Anterior external fixation for pelvic ring fractures has shown to effectively improve stability and reduce mortality. However, these fixators can be associated with substantial morbidity such as pin tract infection, premature loss of fixation, and decreased quality of life in patients. Recently, two new methods of subcutaneous anterior pelvic internal fixation have been developed; the INFIX and the Pelvic Bridge. These methods have the purported advantages of lower wound complications, less surgical site pain, and improved quality of life. We sought to investigate the measured distances to critical anatomic structures, as well as the qualitative and topographic differences notable during implantation of both devices in the same cadaveric specimen. The Pelvic Bridge and INFIX were implanted in eleven fresh cadavers. Distances were then measured to: the superficial inguinal ring, round ligament, spermatic cord, lateral femoral cutaneous nerve (LFCN), femoral nerve, femoral artery, and femoral vein. Observations regarding implantation and topography were also recorded. The INFIX had greater measured distances from all structures except for the LFCN, in which its proximity placed this structure at risk. Neither device appears to put other critical structures at risk in the supine position. Significant implantation and topographic differences exist between the devices. The INFIX application lacked "safety margins" concerning the LFCN in 10/11 (90.9%) specimens, while Pelvic Bridge placement lacked "safety margins" with regard to the right superficial ring (1/11, 9%) and the right spermatic cord (1/11, 9%). Both the Pelvic Bridge and INFIX lie at safe distances from most critical pelvic structures in the supine position, though INFIX application places the LFCN at risk. Copyright © 2017 Elsevier Ltd. All rights reserved.

Anterior Hip Subluxation due to Lumbar Degenerative Kyphosis and Posterior Pelvic Tilt

Directory of Open Access Journals (Sweden)

Hiroyuki Tsuchie

2014-01-01

Full Text Available Nontraumatic anterior subluxation and dislocation of the hip joint are extremely rare. A 58-year-old woman presented to our outpatient clinic with left hip pain with a duration of 15 years. There was no history of trauma or other diseases. Her hip pain usually occurred only on walking and not at rest. Physical examinations demonstrated no tenderness in the hip joint. The range of motion of both hip joints was almost normal. Laxity of other joints was not observed. The bone mineral density of the lumbar spine and proximal femur confirmed a diagnosis of osteoporosis. A plain radiograph showed osteoarthritic changes of the hip joints, severe posterior pelvic tilt, and superior displacement of both femoral heads, especially in a standing position. Three-dimensional computed tomography (3DCT revealed anterior subluxation of both femoral heads. Seven years after the initial visit, both hip joints showed progression to severe osteoarthritis. Although the exact cause remains unclear, lumbar kyphosis, posterior pelvic tilt, and a decrease in acetabular coverage may have influenced the current case. We should be aware of these factors when we examine patients with hip osteoarthritis.

Magnetoresistance effect in permalloy nanowires with various types of notches

Science.gov (United States)

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.

Gauging NOTCH1 Activation in Cancer Using Immunohistochemistry.

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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

Femoral head retroposition as a potential compensatory mechanism in patients with a severe mismatch between pelvic incidence and lumbar lordosis.

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Cheng, Xiaofei; Zhang, Kai; Sun, Xiaojiang; Zhao, Changqing; Li, Hua; Zhao, Jie

2017-12-01

Severe mismatch between pelvic incidence (PI) and lumbar lordosis (LL) leads to extra anterior displacement of the gravity line. The objective of this study is to investigate whether femoral head retroposition is a separate compensatory mechanism responsible for the extra anterior displacement. Based on the values of PI and LL, 94 patients were divided into the PI-LL match group (PI-LL ≤ 0°), the mild PI-LL mismatch group (20°> PI-LL >0°), and the severe PI-LL mismatch group (PI-LL ≥ 20°). A series of parameters including PI, LL, PI-LL, thoracic kyphosis (TK), pelvic tilt (PT), sacral slope (SS), knee flexion angle (KFA), tibial obliquity angle (TOA), sagittal vertical axis (SVA), S1 overhang, femoral head shift (FHS), and pelvic shift (PS) were measured and compared among the three groups. The severe PI-LL mismatch group exhibited significantly greater PI, PI-LL, PT, KFA, SVA, PS, and FHS, and less LL and TK, compared with the control and mild PI-LL mismatch group. The mild PI-LL mismatch group had significantly greater PI-LL, PT, KFA, TOA, and S1 overhang, and less LL and SS than the control group. SS, TOA, and S1 overhang in the severe PI-LL mismatch group differed significantly from that in the control group, but did not differ significantly from that in the mild PI-LL mismatch group. Femoral head retroposition is an entirely separate compensatory mechanism and, in this study, participated in the compensation for the anterior displacement of the gravity line induced by extra-sagittal spinal malalignment in patients with severe PI-LL mismatch.

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

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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.

Assessment of bone quality in the isolated femoral head for intracapsular fractures of the femoral head. Analysis of bone architecture using micro-CT and pQCT, and comparison with extracapsular fractures

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Sando, Masaru

2003-01-01

Block sections were prepared from the five locations, central portion, superior portion, inferior portion, anterior portion, and posterior portion, of the region around the fracture of the femoral head isolated from 21 patients (16 patients with intracapsular fracture, 5 patients with extracapsular fracture). Cancellous bone microstructure, cortical bone thickness, and bone density were evaluated and analyzed for differences in the mechanism from which intracapsular versus extracapsular fracture and fragility developed. The method of evaluating the bone architecture differed from conventional bone histomorphometry of hard tissues and involved non-invasive micro-CT measurements, while the bone density was measured by peripheral quantitative computed topography (pQCT). The results indicate that in comparison to patients with extracapsular fractures, patients with intracapsular fractures showed significant decreases in the trabecular thickness of superior and posterior portions in the cancellous bone. The cortical bone thickness was significantly decreased in the superior portion. Bone density was significantly decreased in the superior portion, while in the extracapsular fracture group density tended to be lower in the inferior, anterior, and posterior portions, although this was not statistically significant. Although there have been previous studies on the bone quality of the femoral head isolated from intracapsular fracture of the femoral head, most reports are of two-dimensional analysis of coronal sections. As far as we are aware, there have been no previous reports comparing individual locations to extracapsular fractures. In view of the various reports that bone density is lower in the extracapsular fracture compared to the intracapsular fracture, we speculate that extracapsular fracture results from the effects of external forces on decreased bone density, while in the intracapsular fracture type, thinning of the superior portion of the cortical bone creates

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

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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.

High levels of Notch signaling down-regulate Numb and Numblike

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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,

3D MRI findings of anterior cruciate ligament reconstruction at follow-up

International Nuclear Information System (INIS)

Deng Jun; Liang Biling; Chen Jianyu; Huang Suiqiao; Zhong Jinglian; Li Xiao

2011-01-01

Objective: To investigate the postoperative 3D MRI appearances and their evolvement patterns of ACL grafts and bone tunnels at follow-up. Methods: There were 2,6 double bundles ACL reconstructions and 16 single bundle ACL reconstructions, and a total of 56 follow-up 3D MR Imaging. MR images were reconstructed with MPR technique to evaluate grafts, bone tunnels, fixers and associated complications. Proportions of grafts with hypointensity or hyperintensity and occurrence rates of marrow edema around bone tunnels were calculated respectively among groups of different periods after operation. Results: There were 2, 4 grafts of hypointensity and 32 grafts of hyperintensity. Grafts of 2 cases were suspended with cross pins within femoral tunnels, graft of 1 case was suspended with an endobutton within the femoral tunnel, and grafts of other sites were fixed with interference screws. In the three periods as 3 months, 6 to 9 months and over 12 months after cruciate ligament reconstruction, proportions of hypointensive grafts were 20/25, 0/14 and 4/10 respectively, while proportions of hyperintensive grafts were 5/25, 14/14 and 6/10 respectively, occurrence proportions of marrow edema around bone tunnels were 54/54, 10/32 and 4/26 respectively. There was 1 tear graft, 4 tibial tunnels placed anteriorly with ACL graft impingement on the intercondylar roof, 3 femoral tunnels placed anteriorly, and 2 bone tunnels with mismatching interference screws. Conclusion: 3D MRI can accurately demonstrate the state of ACL grafts, bone tunnels, fixers and associated complications. Intensity of grafts presented a rise and reduce pattern after operation. (authors)

Magnetoresistance effect in permalloy nanowires with various types of notches

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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.

Inhibitory role of Notch1 in calcific aortic valve disease.

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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.

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

International Nuclear Information System (INIS)

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

The pathological significance of Notch1 in oral squamous cell carcinoma.

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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.

Cam Femoroacetabular Impingement as a Possible Explanation of Recalcitrant Anterior Knee Pain.

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Sanchis-Alfonso, Vicente; Tey, Marc; Monllau, Joan Carles

2016-01-01

We present a case of a patient with chronic anterior knee pain (AKP) recalcitrant to conservative treatment who returned to our office for severe hip pain secondary to Cam femoroacetabular impingement (Cam FAI) at 10 months after the onset of knee pain. This case highlights the fact that the main problem is not in the patella but in the hip in some patients with AKP. We hypothesize that there is an external femoral rotation in order to avoid the impingement and therefore the hip pain in patients with Cam FAI. This functional femoral rotation could provoke a patellofemoral imbalance that may be, in theory, responsible for patellofemoral pain in this particular patient. In our case, Cam FAI resolution was related to the resolution of AKP.

A Rare Case of Morel-Lavallee Syndrome Complicating an Anterior Dislocation of Hip Joint.

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Nekkanti, Supreeth; Vijay, C; Theja, Sujana; Shankar, R Ravi; Verma, Anubhav

2016-01-01

Hip dislocations are serious injuries as hip joint is an extremely stable joint. It requires a significant amount of force to produce such an injury. Anterior dislocations are uncommon. Potential complications of anterior hip dislocations are a neurovascular injury to femoral vessels or acetabular fractures. We report a rare late complication of Morel-Lavallee syndrome occurring 3 weeks after an anterior dislocation of the hip in a 43-year-old male. The patient presented to us with history. Morel-Lavallee syndrome is a rare complication. However if diagnosed early can be successfully treated with minimal burden to the patient. The authors recommend surgeons to have a high index of suspicion for this syndrome and a stringent follow-up examination of the patient.

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

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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.

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

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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

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

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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

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

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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

Radiographic landmarks for locating the femoral origin of the superficial medial collateral ligament.

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Hartshorn, Timothy; Otarodifard, Karimdad; White, Eric A; Hatch, George F Rick

2013-11-01

Little has been written about the use of radiographic landmarks for locating the origin of the superficial medial collateral ligament (sMCL). A standardized radiographic landmark for the sMCL origin using intraoperative fluoroscopic imaging may be of value in aiding the surgeon in accurate femoral tunnel placement in the setting of extensive soft tissue disruption and bony attrition. To determine a reproducible radiographic landmark that will assist in correct femoral tunnel placement in sMCL repair and reconstruction. Descriptive laboratory study. Ten fresh-frozen unmatched human cadaveric knees were dissected, and the origin of the sMCL was exposed. A 2-mm metallic marker was then placed at the center of the femoral origin of the sMCL. True lateral fluoroscopically assisted digital radiographs were obtained of the knee with the posterior and distal femoral condyles overlapping in a standardized fashion. With the use of computer software, reference lines were drawn on the images, creating 4 quadrants. Two independent examiners performed quantitative measurements of the sMCL origin in relation to this axis and to the Blumensaat line. Mean measurements showed the sMCL origin to be closely related to the intersection point of the Blumensaat line and a line drawn distally from the posterior femoral cortex on a true lateral radiograph. The sMCL origin was found at a mean point 1.6 ± 4.3 mm posterior and 4.9 ± 2.1 mm proximal to the intersection of a line paralleling the posterior femoral cortex and a line drawn perpendicular to the posterior femoral cortical line, where it intersects the Blumensaat line. In 5 of 10 specimens, the center of the sMCL origin fell precisely on the Blumensaat line. The remaining specimens had sMCL origins anterior to the Blumensaat line. The femoral origin of the sMCL was found in the proximal and posterior quadrants in 8 of 10 specimens. With a relatively small amount of deviation, the sMCL origin can be consistently identified on a true

PEEK-OPTIMA™ as an alternative to cobalt chrome in the femoral component of total knee replacement: A preliminary study.

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Cowie, Raelene M; Briscoe, Adam; Fisher, John; Jennings, Louise M

2016-11-01

PEEK-OPTIMA ™ (Invibio Ltd, UK) has been considered as an alternative joint arthroplasty bearing material due to its favourable mechanical properties and the biocompatibility of its wear debris. In this study, the potential to use injection moulded PEEK-OPTIMA ™ as an alternative to cobalt chrome in the femoral component of a total knee replacement was investigated in terms of its wear performance. Experimental wear simulation of three cobalt chrome and three PEEK-OPTIMA ™ femoral components articulating against all-polyethylene tibial components was carried out under two kinematic conditions: 3 million cycles under intermediate kinematics (maximum anterior-posterior displacement of 5 mm) followed by 3 million cycles under high kinematic conditions (anterior-posterior displacement 10 mm). The wear of the GUR1020 ultra-high-molecular-weight polyethylene tibial components was assessed by gravimetric analysis; for both material combinations under each kinematic condition, the mean wear rates were low, that is, below 5 mm 3 /million cycles. Specifically, under intermediate kinematic conditions, the wear rate of the ultra-high-molecular-weight polyethylene tibial components was 0.96 ± 2.26 mm 3 /million cycles and 2.44 ± 0.78 mm 3 /million cycle against cobalt chrome and PEEK-OPTIMA ™ implants, respectively (p = 0.06); under high kinematic conditions, the wear rates were 2.23 ± 1.85 mm 3 /million cycles and 4.44 ± 2.35 mm 3 /million cycles, respectively (p = 0.03). Following wear simulation, scratches were apparent on the surface of the PEEK-OPTIMA ™ femoral components. The surface topography of the femoral components was assessed using contacting profilometry and showed a statistically significant increase in measured surface roughness of the PEEK-OPTIMA ™ femoral components compared to the cobalt chrome implants. However, this did not appear to influence the wear rate, which remained linear over the duration of

PEEK-OPTIMA™ as an alternative to cobalt chrome in the femoral component of total knee replacement: A preliminary study

Science.gov (United States)

Cowie, Raelene M; Briscoe, Adam; Fisher, John; Jennings, Louise M

2016-01-01

PEEK-OPTIMA™ (Invibio Ltd, UK) has been considered as an alternative joint arthroplasty bearing material due to its favourable mechanical properties and the biocompatibility of its wear debris. In this study, the potential to use injection moulded PEEK-OPTIMA™ as an alternative to cobalt chrome in the femoral component of a total knee replacement was investigated in terms of its wear performance. Experimental wear simulation of three cobalt chrome and three PEEK-OPTIMA™ femoral components articulating against all-polyethylene tibial components was carried out under two kinematic conditions: 3 million cycles under intermediate kinematics (maximum anterior-posterior displacement of 5 mm) followed by 3 million cycles under high kinematic conditions (anterior-posterior displacement 10 mm). The wear of the GUR1020 ultra-high-molecular-weight polyethylene tibial components was assessed by gravimetric analysis; for both material combinations under each kinematic condition, the mean wear rates were low, that is, below 5 mm3/million cycles. Specifically, under intermediate kinematic conditions, the wear rate of the ultra-high-molecular-weight polyethylene tibial components was 0.96 ± 2.26 mm3/million cycles and 2.44 ± 0.78 mm3/million cycle against cobalt chrome and PEEK-OPTIMA™ implants, respectively (p = 0.06); under high kinematic conditions, the wear rates were 2.23 ± 1.85 mm3/million cycles and 4.44 ± 2.35 mm3/million cycles, respectively (p = 0.03). Following wear simulation, scratches were apparent on the surface of the PEEK-OPTIMA™ femoral components. The surface topography of the femoral components was assessed using contacting profilometry and showed a statistically significant increase in measured surface roughness of the PEEK-OPTIMA™ femoral components compared to the cobalt chrome implants. However, this did not appear to influence the wear rate, which remained linear over the duration of the study. These

Evidence of non-canonical NOTCH signaling

DEFF Research Database (Denmark)

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...

Notch and the awesome power of genetics.

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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)

The role of acetabulum geometry and femoral head-neck ratio in the development of osteoarthritis in young men

DEFF Research Database (Denmark)

Halle, B; Halle, D M; Torfing, T

2007-01-01

and the consequence of acetabular retroversion on standardized x-rays. Men aged 26-55 years who earlier had a total hip arthroplasty were included in the case group. This group was compared to a control-group of men treated as trauma patients. The study indicates that acetabular dysplasia and retroversion......We studied the role of acetabulum geometry and head neck ratio in the development of osteoarthritis of the hip in young men. Contrary to previous studies we evaluated the significance of the anterior, posterior and total coverage of the femoral head, the influence of the femoral neck...... and a relative decreased head neck ratio are associated with osteoarthritis of the hip in young men....

Modifiers of notch transcriptional activity identified by genome-wide RNAi

Directory of Open Access Journals (Sweden)

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.

On short cracks that depart from elastoplastic notch tips

Directory of Open Access Journals (Sweden)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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)

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

International Nuclear Information System (INIS)

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)

Aberrant Regulation of Notch3 Signaling Pathway in Polycystic Kidney Disease.

Science.gov (United States)

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.

The comparison of 5-field conformal radiotherapy techniques for the treatment of prostate cancer: The best for femoral head sparing

International Nuclear Information System (INIS)

Zare, Mahkameh; Lashkari, Marzieh; Ghalehtaki, Reza; Ghasemi, Arash; Dehghan Manshadi, Hamidreza; Mir, Ali; Noorollahi, Somayeh; Alamolhoda, Mahboobeh

2016-01-01

External radiotherapy is a standard treatment procedure for localized prostate cancer. Given the relatively high long term survival treatment complications have been brought in center of attention. In this planning study, between 2012 and 2014, CT simulation data of 90 consecutive high-risk prostate cancer patients were collected. In the first phase, all were planned for whole pelvis irradiation up to 46Gy in 23 daily fractions. In the second phase, only the prostate gland was the target of radiation. Next, the subjects were divided randomly into three groups and each received a unique 5field conformal radiation plan including Plan A (Gantry angle: 0, 60, 120, 240, and 300), Plan B (Gantry angles: 0, 90, 120, 240, and 270) and Plan C (Gantry angles: 0, 60, 90, 270, and 300). The total dose was 70Gy. For each patient, the rectum, bladder, and both femoral heads were contoured as the at risk organs (OAR). From dose volume histograms, the proportional dose of PTV V100, the bladder and rectum V80 and V90 and femoral head V50 and V100 were calculated in all subjects and compared across plans. A statistically significant difference in the femoral head V50 and V100 was found between our studied 5field plans so that in Plan A (beam angles: 0, 60, 120, 240 and 300) less dose was received by both heads of femur. This study suggests that 5 field treatment planning including an anterior, two anterior oblique and two posterior oblique portals to be more proper for 3D conformal radiotherapy in order to spare femoral head with acceptable PTV coverage, and bladder and rectal doses.

The relationship of lateral anatomic structures to exiting guide pins during femoral tunnel preparation utilizing an accessory medial portal.

Science.gov (United States)

Farrow, Lutul D; Parker, Richard D

2010-06-01

Anatomic reconstruction of the anterior cruciate ligament through an accessory medial portal has become increasingly popular. The purpose of this study is to describe the relationship of guide pin exit points to the lateral anatomic structures when preparing the anterior cruciate ligament femoral tunnel through an accessory medial portal. We utilized seven fresh frozen cadaveric knees. Utilizing an anteromedial approach, a guide wire was placed into the center of each bundle's footprint. Each guide wire was advanced through the lateral femoral cortex. The guide pins were passed at 90, 110, and 130 degrees of knee flexion. The distances from each guide pin to the closest relevant structures on the lateral side of the knee were measured. At 90 degrees the posterolateral bundle guide pin was closest to the lateral condyle articular cartilage (mean 5.4 +/- 2.2 mm) and gastrocnemius tendon (mean 5.7 +/- 2.1 mm). At 110 degrees the posterolateral bundle pin was closest to the gastrocnemius tendon (mean 4.5 +/- 3.4 mm). At 130 degrees the posterolateral bundle pin was closest to the gastrocnemius tendon (mean 7.2 +/- 5.5 mm) and lateral collateral ligament (mean 6.8 +/- 2.1 mm). At 90 degrees the anteromedial bundle guide pin was closest to the articular cartilage (mean 2.0 +/- 2.0 mm). At 110 degrees the anteromedial bundle pin was closest to the articular cartilage (mean 7.4 +/- 3.5 mm) and gastrocnemius tendon (mean 12.3 +/- 3.1 mm). At 130 degrees the AM bundle pin was closest to the gastrocnemius tendon (mean 8.2 +/- 3.2 mm) and LCL (mean 15.1 +/- 2.9 mm). Neither guide pin (anteromedial or posterolateral bundle) put the peroneal nerve at risk at any knee flexion angle. At low knee flexion angles the anteromedial and posterolateral bundle guide pins closely approximated multiple lateral structures when using an accessory medial arthroscopic portal. Utilizing higher flexion angles increases the margin of error when preparing both femoral tunnels. During preparation of

Proteolytic regulation of Notch1 receptor activity in cancer

NARCIS (Netherlands)

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)

A simple method for quantitative evaluation of the missing area of the anterior glenoid in anterior instability of the glenohumeral joint

Energy Technology Data Exchange (ETDEWEB)

Barchilon, Vidal S. [Sapir Medical Center, Department of Orthopedic Surgery, Shoulder Service, Kfar-Saba (Israel); Kotz, Eugene [Sapir Medical Center, Department of Imaging, Kfar-Saba (Israel); Barchilon Ben-Av, Mercedes [Achva College of Education, Department of Mathematics, MP Shikmim (Israel); Glazer, Ernesto [Rabin Medical Center, Department of Imaging, Petah Tikva (Israel); Nyska, Meir [Sapir Medical Center, Department of Orthopedic Surgery, Kfar-Saba (Israel)

2008-08-15

The objective of this study was to describe and validate a simple method to quantitatively calculate the missing area of the anterior part of the glenoid in anterior glenohumeral instability. The calculations were developed from three-dimensional (3D)-reconstructed computerized tomography en face images of the glenoid with 'subtraction' of the humeral head in 13 consecutive cases with known anterior glenohumeral joint instability diagnosed by history and clinical examination. The inferior portion of the glenoid was approximated to a true circle whose center was determined by means of a femoral head gauge. The eroded anterior area was calculated as the ratio between the depth (a perpendicular line from the center of the circle to the eroded edge of the anterior glenoid) and the radius of the inferior glenoid circle. This data was then compared to the results obtained by two additional different methods: direct computerized measurements of the missing area and direct computerized measurement of the ratio between the radius and depth, on two dimensional computed tomography (CT) en face view reconstructions of the glenoid. We provide a function that correlates the ratio between depth and radius of the inferior glenoid circle and the area of the missing anterior glenoid. The results obtained by three different methods were comparable. Simple trigonometric calculations showed that a 5% area defect corresponds to 0.8 (12.5%) of the radius of the inferior glenoid, while a 20% area defect corresponds to 0.5 (50%) of the same radius. Using this simple method and the function provided, the eroded area of the anterior part of the glenoid in anterior glenohumeral instability can be calculated preoperatively using a 3D CT reconstruction of the glenoid with 'subtraction' of the humeral head, obviating the need for sophisticated software to obtain this critical information for preoperative decision making. (orig.)

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

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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.)

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

International Nuclear Information System (INIS)

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.)

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Significance of a notch in the otoacoustic emission stimulus spectrum.

Science.gov (United States)

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.

Notch3 marks clonogenic mammary luminal progenitor cells in vivo.

Science.gov (United States)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

Stump entrapment of the anterior cruciate ligament in late childhood and adolescence

Energy Technology Data Exchange (ETDEWEB)

Meyers, Arthur B.; Laor, Tal; Zbojniewicz, Andrew M. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States)

2011-08-15

Displacement of a portion of the torn anterior cruciate ligament (ACL) into the intercondylar notch can cause a focal fibrotic reaction similar to that seen following ACL reconstruction. This displacement, which can result in locking or limitation of knee extension, is termed stump entrapment and is described in adult MR imaging literature. We present a pictorial essay of the etiology and appearance of stump entrapment on MR imaging of the knee in an older child and adolescents and review the significance of this finding. (orig.)

Frequency and distribution of Notch mutations in tumor cell lines

International Nuclear Information System (INIS)

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

Cam Femoroacetabular Impingement as a Possible Explanation of Recalcitrant Anterior Knee Pain

Directory of Open Access Journals (Sweden)

Vicente Sanchis-Alfonso

2016-01-01

Full Text Available We present a case of a patient with chronic anterior knee pain (AKP recalcitrant to conservative treatment who returned to our office for severe hip pain secondary to Cam femoroacetabular impingement (Cam FAI at 10 months after the onset of knee pain. This case highlights the fact that the main problem is not in the patella but in the hip in some patients with AKP. We hypothesize that there is an external femoral rotation in order to avoid the impingement and therefore the hip pain in patients with Cam FAI. This functional femoral rotation could provoke a patellofemoral imbalance that may be, in theory, responsible for patellofemoral pain in this particular patient. In our case, Cam FAI resolution was related to the resolution of AKP.

The importance of Notch signaling in peripheral T-cell lymphomas

DEFF Research Database (Denmark)

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....

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

International Nuclear Information System (INIS)

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

Notched audiograms and noise exposure history in older adults.

Science.gov (United States)

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.

Inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer

Institute of Scientific and Technical Information of China (English)

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.

NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells

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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.

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

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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.

Static and Fatigue Behavior Investigation of Artificial Notched Steel Reinforcement

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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.

Identification of a Paralog-Specific Notch1 Intracellular Domain Degron

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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.

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

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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.

CT false-profile view of the hip: a reproducible method of measuring anterior acetabular coverage using volume CT data

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Needell, Steven D.; Borzykowski, Ross M.; Carreira, Dominic S.; Kozy, John

2014-01-01

To devise a simple, reproducible method of using CT data to measure anterior acetabular coverage that results in values analogous to metrics derived from false-profile radiographs. Volume CT images were used to generate simulated false-profile radiographs and cross-sectional false-profile views by angling a multiplanar reformat 115 through the affected acetabulum relative to a line tangential to the posterior margin of the ischial tuberosities. The anterolateral margin of the acetabulum was localized on the CT false-profile view corresponding with the cranial opening of the acetabular roof. Anterior center edge angle (CEA) was measured between a vertical line passing through the center of the femoral head and a line connecting the center of the femoral head with the anterior edge of the condensed line of the acetabulum (sourcil). Anterior CEA values measured on CT false-profile views of 38 symptomatic hips were compared with values obtained on simulated and projection false-profile radiographs. The CT false-profile view produces a cross-sectional image in the same obliquity as false-profile radiographs. Anterior CEA measured on CT false-profile views were statistically similar to values obtained with false-profile radiographs. CT technologists quickly mastered the technique of generating this view. Inter-rater reliability indicated this method to be highly reproducible. The CT false-profile view is simple to generate and anterior CEA measurements derived from it are similar to those obtained using well-positioned false-profile radiographs. Utilization of CT to assess hip geometry enables precise control of pelvic inclination, eliminates projectional errors, and minimizes limitations of image quality inherent to radiography. (orig.)

CT false-profile view of the hip: a reproducible method of measuring anterior acetabular coverage using volume CT data

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Needell, Steven D.; Borzykowski, Ross M. [Boca Radiology Group, Boca Raton, FL (United States); Carreira, Dominic S.; Kozy, John [Broward Health Orthopedics and Sports Medicine, Fort Lauderdale, FL (United States)

2014-11-15

To devise a simple, reproducible method of using CT data to measure anterior acetabular coverage that results in values analogous to metrics derived from false-profile radiographs. Volume CT images were used to generate simulated false-profile radiographs and cross-sectional false-profile views by angling a multiplanar reformat 115 through the affected acetabulum relative to a line tangential to the posterior margin of the ischial tuberosities. The anterolateral margin of the acetabulum was localized on the CT false-profile view corresponding with the cranial opening of the acetabular roof. Anterior center edge angle (CEA) was measured between a vertical line passing through the center of the femoral head and a line connecting the center of the femoral head with the anterior edge of the condensed line of the acetabulum (sourcil). Anterior CEA values measured on CT false-profile views of 38 symptomatic hips were compared with values obtained on simulated and projection false-profile radiographs. The CT false-profile view produces a cross-sectional image in the same obliquity as false-profile radiographs. Anterior CEA measured on CT false-profile views were statistically similar to values obtained with false-profile radiographs. CT technologists quickly mastered the technique of generating this view. Inter-rater reliability indicated this method to be highly reproducible. The CT false-profile view is simple to generate and anterior CEA measurements derived from it are similar to those obtained using well-positioned false-profile radiographs. Utilization of CT to assess hip geometry enables precise control of pelvic inclination, eliminates projectional errors, and minimizes limitations of image quality inherent to radiography. (orig.)

In vivo analysis of the Notch receptor S1 cleavage.

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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.

The functional role of Notch signaling in human gliomas

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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...

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

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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.

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

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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.

PI3K/AKT signaling inhibits NOTCH1 lysosome-mediated degradation.

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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.

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

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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.

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

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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.

Far infrared promotes wound healing through activation of Notch1 signaling.

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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.

Mandibular Ramus Notching As a Tool for Sexual Dimorphism

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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.

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

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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.

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

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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.

Notch signaling inhibitor DAPT provides protection against acute craniocerebral injury.

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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.

The anterior cruciate ligament: a study on its bony and soft tissue anatomy using novel 3D CT technology.

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Tampere, Thomas; Van Hoof, Tom; Cromheecke, Michiel; Van der Bracht, Hans; Chahla, Jorge; Verdonk, Peter; Victor, Jan

2017-01-01

The purpose of this study is twofold: first, to visualize both the tibial and femoral bony insertion surfaces and second, to describe the anterior cruciate ligament (ACL) geometrically, using novel 3D CT imaging. In addition, new concepts of best-fit cylinder and central axis are introduced and evaluated. Eight unpaired knees of embalmed cadavers were used in this study. Following the dissection process, the ACL was injected with a contrast medium for CT imaging. The obtained CT images in extension, 45°, 90° and full flexion were segmented and rendered in 3D allowing morphological and morphometric analysis of the ACL. Anatomical footprint centres, femoral and tibial footprint surface area, best-fit ACL-cylinder intersection area, best-fit ACL-cylinder/footprint coverage ratio, best-fit ACL-cylinder central axis projections at the tibial and femoral footprint in the four positions were used to describe the anatomy of the ACL, based on the Bernard, Hertel and Amis grid. Based on these parameters, with the best-fit cylinder representing the bulk of the ACL, a changing fibre-recruitment pattern was seen with a moving position of the central axis from posterior to anterior on the femoral and tibial footprint, going from extension to flexion. Furthermore, the numerical data show an increase in tibial footprint coverage by the best-fit cylinder through the ACL when the knee is progressively flexed, whereas an inverse relationship was seen on the femoral side. This study is the first to describe the detailed anatomy of the human ACL with respect to its course and footprints using a 3D approach. It confirms the large difference and inter-patient variability between the tibial and femoral footprint area with the former being significantly smaller. The best-fit cylinder concept illustrates the recruitment pattern of the native ACL where in extension the postero-lateral fibres are recruited and in flexion rather the antero-medial bundle, which can be valuable information in

Treatment of neglected femoral neck fracture

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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

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

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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.

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

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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.

Knee rotation influences the femoral tunnel angle measurement after anterior cruciate ligament reconstruction: a 3-dimensional computed tomography model study

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Tang, Jing; Thorhauer, Eric; Marsh, Chelsea; Fu, Freddie H.

2013-01-01

Purpose Femoral tunnel angle (FTA) has been proposed as a metric for evaluating whether ACL reconstruction was performed anatomically. In clinic, radiographic images are typically acquired with an uncertain amount of internal/external knee rotation. The extent to which knee rotation will influence FTA measurement is unclear. Furthermore, differences in FTA measurement between the two common positions (0° and 45° knee flexion) have not been established. The purpose of this study was to investigate the influence of knee rotation on FTA measurement after ACL reconstruction. Methods Knee CT data from 16 subjects were segmented to produce 3D bone models. Central axes of tunnels were identified. The 0° and 45° flexion angles were simulated. Knee internal/external rotations were simulated in a range of ±20°. FTA was defined as the angle between the tunnel axis and femoral shaft axis, orthogonally projected into the coronal plane. Results Femoral tunnel angle was positively/negatively correlated with knee rotation angle at 0°/45° knee flexion. At 0° knee flexion, FTA for anterio-medial (AM) tunnels was significantly decreased at 20° of external knee rotation. At 45° knee flexion, more than 16° external or 19° internal rotation significantly altered FTA measurements for single-bundle tunnels; smaller rotations (±9° for AM, ±5° for PL) created significant errors in FTA measurements after double-bundle reconstruction. Conclusion Femoral tunnel angle measurements were correlated with knee rotation. Relatively small imaging malalignment introduced significant errors with knee flexed 45°. This study supports using the 0° flexion position for knee radiographs to reduce errors in FTA measurement due to knee internal/external rotation. Level of evidence Case–control study, Level III. PMID:23589127

Complete Absence of Suprascapular Notch: A Case Report

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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.

Expression of Notch1 Correlates with Breast Cancer Progression and Prognosis.

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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.

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

Science.gov (United States)

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.

A Compact Printed Quadruple Band-Notched UWB Antenna

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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.

Free Bone Plug Quadriceps Tendon Harvest and Suspensory Button Attachment for Anterior Cruciate Ligament Reconstruction.

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Todor, Adrian; Caterev, Sergiu; Nistor, Dan Viorel; Khallouki, Youssef

2016-06-01

The most commonly used autografts for anterior cruciate ligament reconstruction are the bone-patellar tendon-bone and hamstring tendons. Each has its advantages and limitations. The bone-patellar tendon-bone autograft can lead to more donor-site morbidity, and the hamstring autograft can be unpredictable in size. The quadriceps tendon, with or without a bone block, has been described as an alternative graft source and has been used especially in revision cases, but in recent years, it has attracted attention even for primary cases. We report a technique for harvesting a free bone quadriceps tendon graft and attaching an extracortical button for femoral fixation for anterior cruciate ligament reconstruction.

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

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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.

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

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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.

Optical stress investigations of notched bars with superimposed types of loads

International Nuclear Information System (INIS)

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

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

International Nuclear Information System (INIS)

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

Notched K-wire for low thermal damage bone drilling.

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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.

A retrospective review of bone tunnel enlargement after anterior cruciate ligament reconstruction with hamstring tendons fixed with a metal round cannulated interference screw in the femur.

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Kobayashi, Masahiko; Nakagawa, Yasuaki; Suzuki, Takashi; Okudaira, Shuzo; Nakamura, Takashi

2006-10-01

To assess bone tunnel enlargement after anterior cruciate ligament (ACL) reconstruction with the use of hamstring tendons fixed with a round cannulated interference (RCI) screw in the femur. A consecutive series of 30 ACL reconstructions performed with hamstring tendons fixed with an RCI screw in the femur and with staples via Leeds-Keio ligament in the tibia was retrospectively reviewed. The clinical outcome was evaluated through the Lysholm score. Anterior instability was tested by Telos-SE (Telos Japan, Tokyo, Japan) measurement. The location and angle of each femoral and tibial tunnel were measured with the use of plain radiographs, and bone tunnel enlargement greater than 2 mm detected any time 3, 6, 12, and 24 months postoperatively was defined as positive. Each factor (location and angle of the tunnels, sex, affected side, age, Lysholm score, and Telos-SE measurement) was compared between enlarged and nonenlarged groups. Positive enlargement of the bone tunnel (>2.0 mm) was observed in 36.7% (11 of 30) on the femoral side and 33.3% (10 of 30) on the tibial side, and in 6 knees of both sides. Half of patients (15 of 30) had an enlarged tunnel on the femoral or the tibial side until 1 year postoperatively. In most cases, enlargement reached maximum at 6 months postoperatively. Female patients tended to have an enlarged tunnel, especially on the femoral side (P < .05). Tunnel enlargement was not correlated with location and angle of the tunnels. Moreover, no difference was found in Lysholm score and Telos-SE measurement between enlarged and nonenlarged groups, although the nonenlarged group tended to exhibit higher Lysholm score and lesser instability. Bone tunnel enlargement of the femoral or tibial side was observed in half of patients (6 in both sides, 5 only in the femur, and 4 only in the tibia) after ACL reconstruction was performed with a hamstring tendon fixed with an RCI screw. Female patients had a greater chance for enlargement of the femoral tunnel

Role of Notch Signaling in Human Breast Cancer Pathogenesis

Science.gov (United States)

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

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

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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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

Science.gov (United States)

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.

Transphyseal ACL Reconstruction in Skeletally Immature Patients: Does Independent Femoral Tunnel Drilling Place the Physis at Greater Risk Compared With Transtibial Drilling?

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Cruz, Aristides I; Lakomkin, Nikita; Fabricant, Peter D; Lawrence, J Todd R

2016-06-01

Most studies examining the safety and efficacy of transphyseal anterior cruciate ligament (ACL) reconstruction for skeletally immature patients utilize transtibial drilling. Independent femoral tunnel drilling may impart a different pattern of distal femoral physeal involvement. To radiographically assess differences in distal femoral physeal disruption between transtibial and independent femoral tunnel drilling. We hypothesized that more oblique tunnels associated with independent drilling involve a significantly larger area of physeal disruption compared with vertically oriented tunnels. Cross-sectional study; Level of evidence, 3. We analyzed skeletally immature patients aged between 10 and 15 years who underwent transphyseal ACL reconstruction utilizing an independent femoral tunnel drilling technique between January 1, 2008, and March 31, 2011. These patients were matched with a transtibial technique cohort based on age and sex. Radiographic measurements were recorded from preoperative magnetic resonance imaging and postoperative radiographs. Ten patients in each group were analyzed. There were significant differences between independent drilling and transtibial drilling cohorts in the estimated area of physeal disruption (1.64 vs 0.74 cm(2); P drilling technique disrupt a larger area of the distal femoral physis and create more eccentric tunnels compared with a transtibial technique. As most studies noting the safety of transphyseal ACL reconstruction have utilized a central, vertical femoral tunnel, surgeons should be aware that if an independent femoral tunnel technique is utilized during transphyseal ACL reconstruction, more physeal tissue is at risk and tunnels are more eccentrically placed across the physis when drilling at more horizontal angles. Prior studies have shown that greater physeal involvement and eccentric tunnels may increase the risk of growth disturbance.

Computer simulation of the Charpy V-notch toughness test

International Nuclear Information System (INIS)

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

Coastal dune dynamics in response to excavated foredune notches

Science.gov (United States)

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

Evaluation of a pig femoral head osteonecrosis model

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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

Rotational malalignment after closed intramedullary nailing of femoral shaft fractures and its influence on daily life.

Science.gov (United States)

Karaman, Ozgur; Ayhan, Egemen; Kesmezacar, Hayrettin; Seker, Ali; Unlu, Mehmet Can; Aydingoz, Onder

2014-10-01

Any intraoperative rotational malalignment during intramedullary nailing (IMN) of femoral shaft fractures will become permanent. We hypothesized that rotational malalignment of the femur and its compensatory biomechanics may induce problems in the hip, knee, patellofemoral and ankle joints. We purposed to clarify the influence of a femoral rotational malalignment of ≥10° on daily activities. Twenty-four femoral shaft fracture patients treated with closed antegrade IMN were included. At last follow-up, to reveal any rotational malalignment, computerized tomography (CT) scans of both femurs (injured and uninjured sides) were examined. The patient groups with or without CT-detected true rotational malalignment ≥10° were compared with respect to the activity scores. Ten of the 24 patients (41.7%) had a CT-detected true rotational malalignment of ≥10° compared with the unaffected side. The AOFAS scores were 100.00 for all of the patients. LKS, WOMAC knee, and WOMAC hip scores were significantly decreased in the patients with rotational malalignment compared to those without. Patients without rotational malalignment tolerated climbing stairs significantly better than those with rotational malalignment. Patients who could not tolerate climbing stairs were consistently complaining of anterior knee pain. A femoral rotational malalignment of ≥10° is symptomatic for the patients, and the hip, knee, and patellofemoral joints were affected. Because of the possibly altered joint loadings and biomechanics, these could render patients prone to degenerative joint disease. In addition, due to the high rates of rotational malalignment after femoral shaft fracture and consequent malpractice claims, it is important for surgeons to be more aware of rotational alignment during surgery.

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

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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.

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

Science.gov (United States)

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.

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

DEFF Research Database (Denmark)

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...

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

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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.

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

Science.gov (United States)

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.

Effect of notch and alloying on steel properties during extension

International Nuclear Information System (INIS)

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

One stage revision single-bundle anterior cruciate ligament reconstruction with impacted morselized bone graft following a failed double-bundle reconstruction

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Ho Jong Ra

2017-01-01

Full Text Available Although double-bundle anterior cruciate ligament (ACL reconstruction has theoretical benefits such as more accurate reproduction of ACL anatomy, it is technically more demanding surgery. This report describes the case of a one stage revision single-bundle ACL reconstruction after primary double-bundle ACL reconstruction. A professional dancer had an ACL previously reconstructed with a double-bundle technique, but the femoral tunnels were malpositioned resulting in residual laxity and rotational instability. The previous femoral tunnel positions were vertical and widened. The previous vertical tunnels were filled with impacted bone graft and a revision single-bundle ACL reconstruction was performed via the new femoral tunnel with a 2 O'clock position between the previous two tunnels. After 10 months of postoperative rehabilitation, the patient returned to professional dancing with sound bony union and without any residual instability.

Insensible is a novel nuclear inhibitor of Notch activity in Drosophila.

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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.

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

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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.

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

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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.

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

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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.

hCLP46 regulates U937 cell proliferation via Notch signaling pathway

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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.

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

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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.

Differences in Femoral Head Penetration Between Highly Cross-Linked Polyethylene Cemented Sockets and Uncemented Liners.

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Morita, Daigo; Seki, Taisuke; Higuchi, Yoshitoshi; Takegami, Yasuhiko; Ishiguro, Naoki

2017-12-01

This study aimed at investigating differences in femoral head penetration between highly cross-linked polyethylene (HXLPE) cemented sockets and uncemented liners during 5 years postoperatively. Ninety-six patients (106 hips) with a mean age of 64.4 (range, 35-83) years underwent total hip arthroplasty using a HXLPE cemented socket or liner and were respectively divided into cemented (35 patients [37 hips]) and uncemented (61 patients [69 hips]) groups. Femoral head penetrations were evaluated on both anteroposterior (AP)-view and Lauenstein-view radiographs, and mean polyethylene (PE) wear rates were calculated based on femoral head penetration from 2 to 5 years. Multivariate analyses were performed to assess risk factors for PE wear. At 5 years postoperatively, the cemented and uncemented groups exhibited proximal direction femoral head penetrations of 0.103 mm and 0.124 mm (P = .226) and anterior direction penetrations of 0.090 mm and 0.151 mm (P = .002), respectively. The corresponding mean PE wear rates were 0.004 mm/y and 0.009 mm/y in the AP-view (P = .286) and 0.005 mm/y and 0.012 mm/y in the Lauenstein-view (P = .168), respectively. Left-side operation and high activity were independent risk factors for PE wear on AP-view. When HXLPE was used, all mean PE wear rates were very low and those of cemented sockets and uncemented liners were very similar. PE particle theory suggests that the occurrence of osteolysis and related aseptic loosening might consequently decrease. Copyright © 2017 Elsevier Inc. All rights reserved.

Femoral morphology and femoropelvic musculoskeletal anatomy of humans and great apes: a comparative virtopsy study.

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Morimoto, Naoki; Ponce de León, Marcia S; Nishimura, Takeshi; Zollikofer, Christoph P E

2011-09-01

The proximal femoral morphology of fossil hominins is routinely interpreted in terms of muscular topography and associated locomotor modes. However, the detailed correspondence between hard and soft tissue structures in the proximal femoral region of extant great apes is relatively unknown, because dissection protocols typically do not comprise in-depth osteological descriptions. Here, we use computed tomography and virtopsy (virtual dissection) for non-invasive examination of the femoropelvic musculoskeletal anatomy in Pan troglodytes, P. paniscus, Gorilla gorilla, Pongo pygmaeus, and Homo sapiens. Specifically, we analyze the topographic relationship between muscle attachment sites and surface structures of the proximal femoral shaft such as the lateral spiral pilaster. Our results show that the origin of the vastus lateralis muscle is anterior to the insertion of gluteus maximus in all examined great ape specimens and humans. In gorillas and orangutans, the insertion of gluteus maximus is on the inferior (anterolateral) side of the lateral spiral pilaster. In chimpanzees, however, the maximus insertion is on its superior (posteromedial) side, similar to the situation in modern humans. These findings support the hypothesis that chimpanzees and humans exhibit a shared-derived musculoskeletal topography of the proximal femoral region, irrespective of their different locomotor modes, whereas gorillas and orangutans represent the primitive condition. Caution is thus warranted when inferring locomotor behavior from the surface topography of the proximal femur of fossil hominins, as the morphology of this region may contain a strong phyletic signal that tends to blur locomotor adaptation. Copyright © 2011 Wiley-Liss, Inc.

Why does necking ignore notches in dynamic tension?

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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.

Multicriteria Decision Analysis in Improving Quality of Design in Femoral Component of Knee Prostheses: Influence of Interface Geometry and Material

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Ali Jahan

2015-01-01

Full Text Available Knee prostheses as medical products require careful application of quality and design tool to ensure the best performance. Therefore, quality function deployment (QFD was proposed as a quality tool to systematically integrate consumer’s expectation to perceived needs by medical and design team and to explicitly address the translation of customer needs into engineering characteristics. In this study, full factorial design of experiment (DOE method was accompanied by finite element analysis (FEA to evaluate the effect of inner contours of femoral component on mechanical stability of the implant and biomechanical stresses within the implant components and adjacent bone areas with preservation of the outer contours for standard Co-Cr alloy and a promising functionally graded material (FGM. The ANOVA revealed that the inner shape of femoral component influenced the performance measures in which the angle between the distal and anterior cuts and the angle between the distal and posterior cuts were greatly influential. In the final ranking of alternatives, using multicriteria decision analysis (MCDA, the designs with FGM was ranked first over the Co-Cr femoral component, but the original design with Co-Cr material was not the best choice femoral component, among the top ranked design with the same material.

Varus femoral osteotomy improves sphericity of the femoral head in older children with severe form of Legg-Calvé-Perthes disease.

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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.

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

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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

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

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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.

The Role of Notch Signaling Pathway in Breast Cancer Pathogenesis

Science.gov (United States)

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

[Trochanteric femoral fractures].

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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

Notch Signaling Pathway Is Activated in Motoneurons of Spinal Muscular Atrophy

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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.

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

African Journals Online (AJOL)

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 ...

Fatigue crack growth from blunt notches

International Nuclear Information System (INIS)

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

Cam Femoroacetabular Impingement as a Possible Explanation of Recalcitrant Anterior Knee Pain

OpenAIRE

Sanchis-Alfonso, Vicente; Tey, Marc; Monllau, Joan Carles

2016-01-01

We present a case of a patient with chronic anterior knee pain (AKP) recalcitrant to conservative treatment who returned to our office for severe hip pain secondary to Cam femoroacetabular impingement (Cam FAI) at 10 months after the onset of knee pain. This case highlights the fact that the main problem is not in the patella but in the hip in some patients with AKP. We hypothesize that there is an external femoral rotation in order to avoid the impingement and therefore the hip pain in patie...

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

International Nuclear Information System (INIS)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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.

Vía de señalización Notch y nuevas estrategias para el tratamiento de cáncer Notch signaling pathway and new strategies in cancer treatment

Directory of Open Access Journals (Sweden)

Leticia Santos

2006-04-01

Full Text Available La vía de señalización Notch desempeña un papel fundamental en las diferentes etapas del desarrollo celular como la proliferación, crecimiento, diferenciación y apoptosis. Estudios recientes han demostrado que, dependiendo del nivel de expresión y del contexto celular, los receptores de membrana Notch contribuyen en la resistencia a apoptosis en células tumorales. Estos descubrimientos sugieren que componentes de la vía de señalización Notch son un blanco potencial para el desarrollo de terapias más efectivas contra el cáncer. Esta revisión describe la función de la vía Notch y nuevas estrategias utilizadas en la modulación de su señal.The Notch signaling pathway plays a crucial role at different stages of cell development, such as proliferation, growth, differentiation, and apoptosis. Recent studies demonstrate that depending on the expression level and cellular context, the Notch receptors play a role in apoptosis resistance in malignant cells. These findings suggest that Notch signaling components may be a potential target in the development of new cancer therapies. This review describes the function of the Notch pathway and new strategies in the modulation of its signal.

Compact microstrip bandpass filter with tunable notch

DEFF Research Database (Denmark)

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....

ALK1 signaling inhibits angiogenesis by cooperating with the Notch pathway.

Science.gov (United States)

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.

Passive notch circuit for pulsed-off compression fields

International Nuclear Information System (INIS)

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

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

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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.

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

Energy Technology Data Exchange (ETDEWEB)

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

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

International Nuclear Information System (INIS)

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

Osteonecrosis of femoral head: Treatment by core decompression and vascular pedicle grafting

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Babhulkar Sudhir

2009-01-01

Full Text Available Background: Femoral head-preserving core decompression and bone grafting have shown excellent result in preventing collapse. The use of vascularized grafts have shown better clinical results. The vascular pedicle bone graft is an easy to perform operation and does not require special equipment. We analyzed and report a series of patients of osteonecrosis of femoral head treated by core decompression and vascular pedicle grafting of part of iliac crest based on deep circumflex iliac vessels. Materials and Methods: The article comprises of the retrospective study of 31 patients of osteonecrosis of femoral head in stage II and III treated with core decompression and vascular pedicle grafting by using part of iliac crest with deep circumflex iliac vessels from January 1990 to December 2005. The young patients with a mean age 32 years (18-52 years with a minimum follow-up of five years were included for analysis. Sixteen patients had osteonecrosis following alcohol abuse, 12 patients following corticosteroid consumption, 3 patients had idiopathic osteonecrosis. Nine patients were stage IIB, and 22 patients were stage IIIC according to ARCO′s system. The core decompression and vascular pedicle grafting was performed by anterior approach by using part of iliac crest with deep circumflex iliac vessels. Results: Digital subtraction arteriography performed in 9 patients at the end of 12 weeks showed the patency of deep circumflex artery in all cases, and bone scan performed in 6 other patients showed high uptake in the grafted area of the femoral head proving the efficacy of the operative procedure. Out of 31 patients, only one patient progressed to collapse and total joint replacement was advised. At the final follow up period of 5-8 years, Harris Hip Score improved mean ± SD of 28.2 ± 6.4 ( p < 0.05. Forty-eight percent of patients had an improvement in Harris Hip Score of more that 28 points. Conclusion: The core decompression and vascular pedicle

Femoral head avascular necrosis

International Nuclear Information System (INIS)

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

Early Clinical and Radiographic Results of Minimally Invasive Anterior Approach Hip Arthroplasty

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Tamara Alexandrov

2014-01-01

consecutive patients with 43 total hip arthroplasties performed through an anterior muscle sparing minimally invasive approach. We found the early complication rates and radiographic outcomes comparable to those reported from arthroplasties performed via traditional approaches. Complications included dislocation (2%, femur fracture (2%, greater trochanteric fracture (12%, postoperative periprosthetic intertrochanteric fracture (2%, femoral nerve palsy (5%, hematoma (2%, and postoperative iliopsoas avulsion (2%. Radiographic analysis revealed average cup anteversion of 19.6°±6.6, average cup abduction angle of 48.4°±7, stem varus of 0.9°±2, and a mean leg length discrepancy of 0.7 mm. The anterior approach to the hip is an attractive alternative to the more traditional approaches. Acceptable component placement with comparable complication rates is possible using a muscle sparing technique which may lead to faster overall recovery.

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

DEFF Research Database (Denmark)

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...

Femoral revision with impaction allografting and an uncemented femoral component

DEFF Research Database (Denmark)

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...

Squatting-Related Tibiofemoral Shear Reaction Forces and a Biomechanical Rationale for Femoral Component Loosening

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Ashvin Thambyah

2014-01-01

Full Text Available Previous gait studies on squatting have described a rapid reversal in the direction of the tibiofemoral joint shear reaction force when going into a full weight-bearing deep knee flexion squat. The effects of such a shear reversal have not been considered with regard to the loading demand on knee implants in patients whose activities of daily living require frequent squatting. In this paper, the shear reversal effect is discussed and simulated in a finite element knee implant-bone model, to evaluate the possible biomechanical significance of this effect on femoral component loosening of high flexion implants as reported in the literature. The analysis shows that one of the effects of the shear reversal was a switch between large compressive and large tensile principal strains, from knee extension to flexion, respectively, in the region of the anterior flange of the femoral component. Together with the known material limits of cement and bone, this large mismatch in strains as a function of knee position provides new insight into how and why knee implants may fail in patients who perform frequent squatting.

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

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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)

Broadband notch filter design for millimeter-wave plasma diagnostics

DEFF Research Database (Denmark)

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...

Notch pathway signaling in the skin antagonizes Merkel cell development.

Science.gov (United States)

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.

[Ex vivo microCT analysis of possible microfractures of the femoral head during implantation of a cementless hip resurfacing femoral component].

Science.gov (United States)

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.

Dangerous Liaisons: Deviant Endothelium NOTCHes toward Tumor Metastasis.

Science.gov (United States)

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.

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

NARCIS (Netherlands)

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

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

International Nuclear Information System (INIS)

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

Femoral Component External Rotation Affects Knee Biomechanics: A Computational Model of Posterior-stabilized TKA.

Science.gov (United States)

Kia, Mohammad; Wright, Timothy M; Cross, Michael B; Mayman, David J; Pearle, Andrew D; Sculco, Peter K; Westrich, Geoffrey H; Imhauser, Carl W

2018-01-01

The correct amount of external rotation of the femoral component during TKA is controversial because the resulting changes in biomechanical knee function associated with varying degrees of femoral component rotation are not well understood. We addressed this question using a computational model, which allowed us to isolate the biomechanical impact of geometric factors including bony shapes, location of ligament insertions, and implant size across three different knees after posterior-stabilized (PS) TKA. Using a computational model of the tibiofemoral joint, we asked: (1) Does external rotation unload the medial collateral ligament (MCL) and what is the effect on lateral collateral ligament tension? (2) How does external rotation alter tibiofemoral contact loads and kinematics? (3) Does 3° external rotation relative to the posterior condylar axis align the component to the surgical transepicondylar axis (sTEA) and what anatomic factors of the femoral condyle explain variations in maximum MCL tension among knees? We incorporated a PS TKA into a previously developed computational knee model applied to three neutrally aligned, nonarthritic, male cadaveric knees. The computational knee model was previously shown to corroborate coupled motions and ligament loading patterns of the native knee through a range of flexion. Implant geometries were virtually installed using hip-to-ankle CT scans through measured resection and anterior referencing surgical techniques. Collateral ligament properties were standardized across each knee model by defining stiffness and slack lengths based on the healthy population. The femoral component was externally rotated from 0° to 9° relative to the posterior condylar axis in 3° increments. At each increment, the knee was flexed under 500 N compression from 0° to 90° simulating an intraoperative examination. The computational model predicted collateral ligament forces, compartmental contact forces, and tibiofemoral internal/external and

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

Science.gov (United States)

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

A Morphological Insight of the Femoral Vein

Directory of Open Access Journals (Sweden)

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.

Distal femoral bone mineral density decreases following patellofemoral arthroplasty: 1-year follow-up study of 14 patients

Directory of Open Access Journals (Sweden)

Innocenti Bernardo

2010-04-01

Full Text Available Abstract Background The bone mineral density (BMD of the distal femur decreases by 16-36% within one year after total knee arthroplasty (TKA because of the femoral component's stress-shielding effect. The aim of this prospective study was to determine the quantitative change from the baseline BMD in the distal femur 1 year after patellofemoral arthroplasty using dual-energy X-ray absorptiometry (DXA. Methods Between December 2007 and December 2008, 14 patients had patellofemoral arthroplasty for isolated patellofemoral osteoarthritis. Distal femoral BMD was assessed using DXA in 2 regions of interest (ROI on the lateral view 2 weeks before and 12 months after patellofemoral arthroplasty. The contra-lateral knee was used as a control, with BMD measurements performed in identical ROIs. Results The mean change from baseline BMD in the operated knees after 1 year was -0.169 g/cm2 (95% CI: -0.293 to -0.046 g/cm2 behind the anterior flange (-15%, and -0.076 g/cm2 (95% CI: -0.177 to 0.024 g/cm2 in the supracondylar area 1 cm above the prosthesis (-8% (p = 0.01 and p = 0.13, respectively. The mean change from baseline BMD in the non-operated knees after 1 year was 0.016 g/cm2 (95% CI: -0.152 to 0.185 g/cm2 behind the anterior flange (2%, and 0.023 g/cm2 (95% CI: -0.135 to 0.180 g/cm2 in the supracondylar area 1 cm above the prosthesis (2% (p = 0.83, and p = 0.76, respectively. Conclusions Our findings suggest that patellofemoral arthroplasty results in a statistically significant decrease in BMD behind the anterior flange.

Does the Watson-Jones or Modified Smith-Petersen Approach Provide Superior Exposure for Femoral Neck Fracture Fixation?

Science.gov (United States)

Lichstein, Paul M; Kleimeyer, John P; Githens, Michael; Vorhies, John S; Gardner, Michael J; Bellino, Michael; Bishop, Julius

2018-04-24

has broad applications and is frequently used in other subspecialties such as for direct anterior THA and pediatric septic hip drainage. Surgeons treating femoral neck fractures with open reduction and fixation should familiarize themselves with the modified Smith-Petersen approach.

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

DEFF Research Database (Denmark)

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...

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

DEFF Research Database (Denmark)

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...

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Bone contusions in the adolescent knee: confusion with rupture of anterior cruciate ligament

International Nuclear Information System (INIS)

Roca, M.; Mota, J.; Guedea, A.

1998-01-01

One of the most specific secondary findings, on magnetic resonance imaging, associated with acute rupture of anterior cruciate ligament (ACL) are bone contusions of lateral femoral condyle or tibial plateau.Given the marked specificity of these indirect findings (97% to 100%), their presence corroborates the diagnosis of ACL tears. The unreliability of these signs in adolescents has recently been reported. We present a case of subchondral bone contusion with intact ACL, the knowledge of which may prevent potential misinterpretations and unnecessary arthroscopic examinations. (Author) 9 refs

Ipsilateral open anterior hip dislocation and open posterior elbow dislocation in an adult

Directory of Open Access Journals (Sweden)

Kumar Sunil

2014-02-01

Full Text Available 【Abstract】Open anterior dislocation of the hip is a very rare injury, especially in adults. It is a hyperabduction, external rotation and extension injury. Its combination with open posterior dislocation of the elbow has not been described in English language-based medical literature. Primary resuscitation, debridement, urgent reduction of dislocation, and adequate antibiotic support resulted in good clinical outcome in our patient. At 18 months follow-up, no signs of avascular necrosis of the femoral head or infection were observed.

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

Science.gov (United States)

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.

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

OpenAIRE

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...

Identification of a Paralog-Specific Notch1 Intracellular Domain Degron

OpenAIRE

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...

Passive Anterior Tibial Subluxation in the Setting of Anterior Cruciate Ligament Injuries: A Comparative Analysis of Ligament-Deficient States.

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McDonald, Lucas S; van der List, Jelle P; Jones, Kristofer J; Zuiderbaan, Hendrik A; Nguyen, Joseph T; Potter, Hollis G; Pearle, Andrew D

2017-06-01

Static anterior tibial subluxation after an anterior cruciate ligament (ACL) injury highlights the abnormal relationship between the tibia and femur in patients with ACL insufficiency, although causal factors including injuries to secondary stabilizers or the time from injury to reconstruction have not been examined. To determine static relationships between the tibia and femur in patients with various states of ACL deficiency and to identify factors associated with anterior tibial subluxation. Cross-sectional study; Level of evidence, 3. Patients treated for ACL injuries were identified from an institutional registry and assigned to 1 of 4 cohorts: intact ACL, acute ACL disruption, chronic ACL disruption, and failed ACL reconstruction (ACLR). Anterior tibial subluxation of the medial and lateral compartments relative to the femoral condyles were measured on magnetic resonance imaging (MRI), and an MRI evaluation for meniscal tears, chondral defects, and injuries to the anterolateral ligament (ALL) was performed. One hundred eighty-six ACL-insufficient knees met inclusion criteria, with 26 patients without an ACL injury utilized as a control group. In the lateral compartment, the mean anterior tibial subluxation measured 0.78 mm for the control group (n = 26), 2.81 mm for the acute ACL injury group (n = 74), 3.64 mm for the chronic ACL injury group (n = 40), and 4.91 mm for the failed ACLR group (n = 72). In the failed ACLR group, 37.5% of patients demonstrated lateral compartment anterior subluxation ≥6 mm, and 11.1% of this group had anterior subluxation of the lateral compartment ≥10 mm. Multivariate regression revealed that the presence of both medial and lateral chondral defects was associated with a mean 1.09-mm increase in subluxation of the medial compartment ( P = .013). The combination of medial and lateral meniscal tears was an independent predictor of increased lateral tibia subluxation by 1.611 mm ( P = .0022). Additionally, across all knee states

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

African Journals Online (AJOL)

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 ...

Notch sensitivity of ductile metallic foams : A computational study

NARCIS (Netherlands)

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)

Failure of a porous solid from a deep notch

DEFF Research Database (Denmark)

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...

Endocardial to myocardial notch-wnt-bmp axis regulates early heart valve development.

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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.

Femoral shaft fractures

International Nuclear Information System (INIS)

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

Notch signaling mediates granulocyte-macrophage colony-stimulating factor priming-induced transendothelial migration of human eosinophils.

Science.gov (United States)

Liu, L Y; Wang, H; Xenakis, J J; Spencer, L A

2015-07-01

Priming with cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances eosinophil migration and exacerbates the excessive accumulation of eosinophils within the bronchial mucosa of asthmatics. However, mechanisms that drive GM-CSF priming are incompletely understood. Notch signaling is an evolutionarily conserved pathway that regulates cellular processes, including migration, by integrating exogenous and cell-intrinsic cues. This study investigates the hypothesis that the priming-induced enhanced migration of human eosinophils requires the Notch signaling pathway. Using pan Notch inhibitors and newly developed human antibodies that specifically neutralize Notch receptor 1 activation, we investigated a role for Notch signaling in GM-CSF-primed transmigration of human blood eosinophils in vitro and in the airway accumulation of mouse eosinophils in vivo. Notch receptor 1 was constitutively active in freshly isolated human blood eosinophils, and inhibition of Notch signaling or specific blockade of Notch receptor 1 activation during GM-CSF priming impaired priming-enhanced eosinophil transendothelial migration in vitro. Inclusion of Notch signaling inhibitors during priming was associated with diminished ERK phosphorylation, and ERK-MAPK activation was required for GM-CSF priming-induced transmigration. In vivo in mice, eosinophil accumulation within allergic airways was impaired following systemic treatment with Notch inhibitor, or adoptive transfer of eosinophils treated ex vivo with Notch inhibitor. These data identify Notch signaling as an intrinsic pathway central to GM-CSF priming-induced eosinophil tissue migration. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An expanded Notch-Delta model exhibiting long-range patterning and incorporating MicroRNA regulation.

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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.

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

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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.

Mastermind-Like 1 Is Ubiquitinated: Functional Consequences for Notch Signaling.

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Mozhgan Farshbaf

Full Text Available Early studies demonstrated the involvement of ubiquitination of the Notch intracellular domain for rapid turnover of the transcriptional complex at Notch target genes. It was shown that this ubiquitination was promoted by the co-activator Mastermind like 1 (MAML1. MAML1 also contains numerous lysine residues that may also be ubiquitinated and necessary for protein regulation. In this study, we show that over-expressed MAML1 is ubiquitinated and identify eight conserved lysine residues which are required for ubiquitination. We also show that p300 stimulates ubiquitination and that Notch inhibits ubiquitination. Furthermore, we show that a mutant MAML1 that has decreased ubiquitination shows increased output from a HES1 reporter gene assay. Therefore, we speculate that ubiquitination of MAML1 might be a mechanism to maintain low levels of the protein until needed for transcriptional activation. In summary, this study identifies that MAML1 is ubiquitinated in the absence of Notch signaling to maintain low levels of MAML1 in the cell. Our data supports the notion that a precise and tight regulation of the Notch pathway is required for this signaling pathway.

A Novel Notch-YAP Circuit Drives Stemness and Tumorigenesis in Embryonal Rhabdomyosarcoma.

Science.gov (United States)

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.

Immunohistochemical expression of Notch signaling in the lining epithelium of periapical cysts.

Science.gov (United States)

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.

Effect of Notches on Creep-Fatigue Behavior of a P/M Nickel-Based Superalloy

Science.gov (United States)

Telesman, Jack; Gabb, Timothy P.; Ghosn, Louis J.; Gayda, John, Jr.

2015-01-01

A study was performed to determine and model the effect of high temperature dwells on notched low cycle fatigue (NLCF) and notch stress rupture behavior of a fine grain LSHR powder metallurgy (PM) nickel-based superalloy. It was shown that a 90 second dwell applied at the minimum stress (min dwell) was considerably more detrimental to the NLCF lives than similar dwell applied at the maximum stress (max dwell). The short min dwell NLCF lives were shown to be caused by growth of small oxide blisters which caused preferential cracking when coupled with high concentrated notch root stresses. The cyclic max dwell notch tests failed mostly by a creep accumulation, not by fatigue, with the crack origin shifting internally to a substantial distance away from the notch root. The classical von Mises plastic flow model was unable to match the experimental results while the hydrostatic stress profile generated using the Drucker-Prager plasticity flow model was consistent with the experimental findings. The max dwell NLCF and notch stress rupture tests exhibited substantial creep notch strengthening. The triaxial Bridgman effective stress parameter was able to account for the notch strengthening by collapsing the notched and uniform gage geometry test data into a singular grouping.

Subchondral insufficiency fractures of the femoral head

Energy Technology Data Exchange (ETDEWEB)

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.)

Asymmetric cell division and Notch signaling specify dopaminergic neurons in Drosophila.

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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.

Mapping Sites of O-Glycosylation and Fringe Elongation on Drosophila Notch*

Science.gov (United States)

Harvey, Beth M.; Rana, Nadia A.; Moss, Hillary; Leonardi, Jessica; Jafar-Nejad, Hamed; Haltiwanger, Robert S.

2016-01-01

Glycosylation of the Notch receptor is essential for its activity and serves as an important modulator of signaling. Three major forms of O-glycosylation are predicted to occur at consensus sites within the epidermal growth factor-like repeats in the extracellular domain of the receptor: O-fucosylation, O-glucosylation, and O-GlcNAcylation. We have performed comprehensive mass spectral analyses of these three types of O-glycosylation on Drosophila Notch produced in S2 cells and identified peptides containing all 22 predicted O-fucose sites, all 18 predicted O-glucose sites, and all 18 putative O-GlcNAc sites. Using semiquantitative mass spectral methods, we have evaluated the occupancy and relative amounts of glycans at each site. The majority of the O-fucose sites were modified to high stoichiometries. Upon expression of the β3-N-acetylglucosaminyltransferase Fringe with Notch, we observed varying degrees of elongation beyond O-fucose monosaccharide, indicating that Fringe preferentially modifies certain sites more than others. Rumi modified O-glucose sites to high stoichiometries, although elongation of the O-glucose was site-specific. Although the current putative consensus sequence for O-GlcNAcylation predicts 18 O-GlcNAc sites on Notch, we only observed apparent O-GlcNAc modification at five sites. In addition, we performed mass spectral analysis on endogenous Notch purified from Drosophila embryos and found that the glycosylation states were similar to those found on Notch from S2 cells. These data provide foundational information for future studies investigating the mechanisms of how O-glycosylation regulates Notch activity. PMID:27268051

Automated 3D quantitative assessment and measurement of alpha angles from the femoral head-neck junction using MR imaging

Science.gov (United States)

Xia, Ying; Fripp, Jurgen; Chandra, Shekhar S.; Walker, Duncan; Crozier, Stuart; Engstrom, Craig

2015-10-01

To develop an automated approach for 3D quantitative assessment and measurement of alpha angles from the femoral head-neck (FHN) junction using bone models derived from magnetic resonance (MR) images of the hip joint. Bilateral MR images of the hip joints were acquired from 30 male volunteers (healthy active individuals and high-performance athletes, aged 18-49 years) using a water-excited 3D dual echo steady state (DESS) sequence. In a subset of these subjects (18 water-polo players), additional True Fast Imaging with Steady-state Precession (TrueFISP) images were acquired from the right hip joint. For both MR image sets, an active shape model based algorithm was used to generate automated 3D bone reconstructions of the proximal femur. Subsequently, a local coordinate system of the femur was constructed to compute a 2D shape map to project femoral head sphericity for calculation of alpha angles around the FHN junction. To evaluate automated alpha angle measures, manual analyses were performed on anterosuperior and anterior radial MR slices from the FHN junction that were automatically reformatted using the constructed coordinate system. High intra- and inter-rater reliability (intra-class correlation coefficients  >  0.95) was found for manual alpha angle measurements from the auto-extracted anterosuperior and anterior radial slices. Strong correlations were observed between manual and automatic measures of alpha angles for anterosuperior (r  =  0.84) and anterior (r  =  0.92) FHN positions. For matched DESS and TrueFISP images, there were no significant differences between automated alpha angle measures obtained from the upper anterior quadrant of the FHN junction (two-way repeated measures ANOVA, F  hip joints to generate alpha angle measures around the FHN junction circumference with very good reliability and reproducibility. This work has the potential to improve analyses of cam-type lesions of the FHN junction for large

Is Botulinum Toxin Type A a Valuable Adjunct During Femoral Lengthening? A Randomized Trial.

Science.gov (United States)

Park, Hoon; Shin, Soowan; Shin, Han Sol; Kim, Hyun Woo; Kim, Dong Wook; Lee, Dong Hoon

2016-12-01

Reduced joint ROM and distraction-induced pain are common complaints of patients who have undergone gradual femoral lengthening. Attempts to reduce the effects of lengthening on joint motion have included the use of botulinum toxin to reduce the muscle forces that restrict motion. The benefits of this approach during femoral lengthening, however, have not been conclusively established. We wished to evaluate the effects of botulinum toxin type A (BtX-A) injection in the anterior thigh muscles during femoral distraction osteogenesis on adjacent joint ROM and distraction-induced pain. We asked: (1) Does injection of BtX-A in the quadriceps muscles lead to improved knee and hip motion during femoral lengthening? (2) Does injection of BtX-A reduce pain during femoral lengthening? A single-center, double-blind, randomized placebo-controlled trial was conducted. Forty-four patients (88 femurs) undergoing bilateral femoral lengthening for familial short stature were included in the study. BtX-A (200 IU) was injected intraoperatively in the quadriceps muscles of one thigh. An equal volume of sterile normal saline was injected in the other thigh as a control. Selection of the limb receiving the toxin was randomized. Clinical evaluation included a VAS score for pain measurement, ROM evaluation of the hips and knees, and measurement of thigh circumference. Side-to-side differences were analyzed throughout the entire consolidation phase. No patients were lost to followup, leaving 44 patients (88 femurs). The mean followup was 26 months (range, 14-40 months). The distraction rate and final length of gain were similar between treated and control limbs. A priori power analysis suggested that 44 legs were required in each group to achieve statistical significance of 0.05 with 90% power to detect a 50% difference in treatment effect between treatment and control groups. There were no differences in hip ROM, knee ROM, or maximal thigh circumference between the two lower extremities

Management of Femoral Shaft Fractures with Elastic Titanium Nails in Pediatric Patients

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Yunus Güzel

2016-06-01

Full Text Available Objective: The aim of this study was to evaluate the func­tional and radiological results of the application of intra­medullary fixation with elastic titanium nails in unstable femoral fractures and to determine the factors affecting these results. Methods: A total of 32 patients aged 4-17 years treated with intramedullary elastic nails for a femoral diaphysis fracture between 2001 and 2014 were included. The frac­ture was left side in 12 cases, right side in 18 and bilateral in 2. The fracture pattern was determined as fragmented in 11 cases, short oblique in 11, transverse in 8 and spi­ral in 4. The same surgical technique and postoperative care was applied to all the patients. Sagittal and coronal angle measurements were made from postoperative and follow-up anterior-posterior and lateral radiographs. The mean follow-up period was 54 months (12-156 months. Positive union criteria were accepted as pain-free weight-bearing and callus bridging in at least 3 cortices seen on direct radiographs. Results: Union was achieved in all except one patient. They were able to return to previous activities with full knee and hip joint range of movement. Radiologically, the mean time to union was determined as 9 weeks (range, 6-16 weeks. Limb shortness was determined in 5 (14% patients. No significant association was detected be­tween shortness and fracture pattern. No varus or valgus angulation of >10˚ was determined in any patient. Conclusion: Application of titanium elastic nails in pe­diatric femoral diaphysis fractures is a comfortable, eco­nomic, and reliable method which is allows early weight-bearing.

Notch signalling mediates reproductive constraint in the adult worker honeybee

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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

Case report: AVN of the femoral head five year follow-up of the combination of ipsilateral femoral neck and sub-trochanteric fracture.

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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.

Inhibition of Notch signaling alters the phenotype of orthotopic tumors formed from glioblastoma multiforme neurosphere cells but does not hamper intracranial tumor growth regardless of endogene Notch pathway signature

DEFF Research Database (Denmark)

Kristoffersen, Karina; Nedergaard, Mette Kjølhede; Villingshøj, Mette

2014-01-01

BACKGROUND: Brain cancer stem-like cells (bCSC) are cancer cells with neural stem cell (NSC)-like properties found in the devastating brain tumor glioblastoma multiforme (GBM). bCSC are proposed a central role in tumor initiation, progression, treatment resistance and relapse and as such present...... a promising target in GBM research. The Notch signaling pathway is often deregulated in GBM and we have previously characterized GBM-derived bCSC cultures based on their expression of the Notch-1 receptor and found that it could be used as predictive marker for the effect of Notch inhibition. The aim...... of the present project was therefore to further elucidate the significance of Notch pathway activity for the tumorigenic properties of GBM-derived bCSC. METHODS: Human-derived GBM xenograft cells previously established as NSC-like neurosphere cultures were used. Notch inhibition was accomplished by exposing...

Clinical impact of de-regulated Notch-1 and Notch-3 in the development and progression of HPV-associated different histological subtypes of precancerous and cancerous lesions of human uterine cervix.

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Richa Tripathi

Full Text Available Cervical cancer is the leading cause of cancer related deaths among women in India. Limited reports are available for Notch-1 and Notch-3 protein in cervical carcinoma, which play crucial role in cell proliferation, differentiation, and apoptosis.This study was designed to evaluate the role of Notch-1 and Notch-3 with context to HPV infection in cervical carcinoma. A total of 168 tissue biopsy samples comprising of tumor specimens (n = 98, precancer (n = 30 and non-neoplastic cervical tissues (n = 40 were screened for HPV infection by PCR and expression of Notch-1 and Notch-3 protein by Immunohistochemistry and Immunoblotting.80% (24/30 were found to be positive for HPV in precancer and 86.7% (85/98 in cancer patients. Notch-1 expression of precancer and cancer cases was found to be significantly down-regulated with severity of disease in nuclear (3.43±0.29; 2.04±0.19, p = 0.0001, p = 0.0001 and cytoplasm (3.07±0.29; 2.29±0.17, p = 0.0001, p = 0.0001 obtained from different stages as compared to normal cervix tissue (5.40±0.19, 4.97±0.15; p<0.001; p<0.001. However, Notch-3 expression of above cases was significantly up-regulated with severity of disease and showed intense nuclear (4.17±0.39; 4.74±0.18, p = 0.0001, p = 0.0001 and cytoplasm (3.67±0.36; 4.48±0.18, p = 0.0001, p = 0.0001 of different stages as compared to normal cervix tissue (0.95±0.20, 0.70±0.20; p<0.001; p<0.001 respectively.These findings suggest that Notch-1 and Notch-3 may play an important role with synergistic effect of HPV in regulating development and proliferation of cervical cancer through the deregulation of Notch signalling. This study also shows the clinical utility of both proteins which may be used as predictable biomarkers in diagnosing different histological sub-types of HPV associated cervical cancer. Nevertheless, abnormal activation of this pathway may provide legitimate targets for cervical cancer therapy.

Fracturing of revision of a cobalt-chrome femoral head after fracturing of a ceramic femoral head, with diffuse metallosis. Case report

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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

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

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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.

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

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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.

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.

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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

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

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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.

Theoretical and experimental study of Chen chaotic system with notch filter feedback control

International Nuclear Information System (INIS)

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)

Slipped capital femoral epiphysis: A modern treatment protocol

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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.

Genetic screens to identify new Notch pathway mutants in Drosophila.

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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.

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

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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.

Effect of delaminations on improvement of notch toughness at low temperatures

International Nuclear Information System (INIS)

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

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

African Journals Online (AJOL)

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 ...

Notch2 transduction by feline leukemia virus in a naturally infected cat.

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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.

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

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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.

Post-operative 3D CT feedback improves accuracy and precision in the learning curve of anatomic ACL femoral tunnel placement.

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Sirleo, Luigi; Innocenti, Massimo; Innocenti, Matteo; Civinini, Roberto; Carulli, Christian; Matassi, Fabrizio

2018-02-01

To evaluate the feedback from post-operative three-dimensional computed tomography (3D-CT) on femoral tunnel placement in the learning process, to obtain an anatomic anterior cruciate ligament (ACL) reconstruction. A series of 60 consecutive patients undergoing primary ACL reconstruction using autologous hamstrings single-bundle outside-in technique were prospectively included in the study. ACL reconstructions were performed by the same trainee-surgeon during his learning phase of anatomic ACL femoral tunnel placement. A CT scan with dedicated tunnel study was performed in all patients within 48 h after surgery. The data obtained from the CT scan were processed into a three-dimensional surface model, and a true medial view of the lateral femoral condyle was used for the femoral tunnel placement analysis. Two independent examiners analysed the tunnel placements. The centre of femoral tunnel was measured using a quadrant method as described by Bernard and Hertel. The coordinates measured were compared with anatomic coordinates values described in the literature [deep-to-shallow distance (X-axis) 28.5%; high-to-low distance (Y-axis) 35.2%]. Tunnel placement was evaluated in terms of accuracy and precision. After each ACL reconstruction, results were shown to the surgeon to receive an instant feedback in order to achieve accurate correction and improve tunnel placement for the next surgery. Complications and arthroscopic time were also recorded. Results were divided into three consecutive series (1, 2, 3) of 20 patients each. A trend to placing femoral tunnel slightly shallow in deep-to-shallow distance and slightly high in high-to-low distance was observed in the first and the second series. A progressive improvement in tunnel position was recorded from the first to second series and from the second to the third series. Both accuracy (+52.4%) and precision (+55.7%) increased from the first to the third series (p process to improve accuracy and precision of femoral

Identification of 11-amino acid peptides that disrupt Notch-mediated processes in Drosophila

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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

Tensile behavior of unnotched and notched tungsten--copper laminar composites

International Nuclear Information System (INIS)

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)

Some observations on the nature of the audiometric 4000 hz notch: data from 3430 veterans.

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Wilson, Richard H

2011-01-01

Pure-tone, air-conduction audiograms notched at 4000 Hz have long been considered the signature configuration for noise-induced hearing loss even though there is an extensive literature that does not mesh with this simple explanation. There are many reports of notched audiograms from individuals with no history of noise exposure and, conversely, reports of audiograms with no notches from individuals with a history of noise exposure. Recent reports increasingly suggest that unilateral 4000 Hz notches are common. The prevalence of notched audiograms at 4000 Hz is dependent on the definition of the notch and the population under study. To examine the prevalence and characteristics of audiograms that are notched at 4000 Hz. Retrospective, descriptive. The participants were 3430 veterans evaluated in the Audiology Clinic at the VA Medical Center, Mountain Home, Tennessee. The mean age was 62.3 yr. Data Collection and Analyses: The data were collected in the course of a 60 min, routine audiological evaluation. In addition to pure-tone audiometry, a history, otoscopy, speech audiometry in quiet and in noise, and aural-acoustic immittance measures were included in the clinic protocol but were not evaluated in this report. A notch was defined when the 4000 Hz threshold minus the 2000 Hz threshold and the 4000 Hz threshold minus the 8000 Hz threshold both were ≥10 dB. Overall the mean LE (left ear) thresholds at 2000, 3000, and 4000 Hz were at hearing levels 2-3 dB higher than the hearing levels for the corresponding mean RE (right ear) thresholds; the differences were significant. A notched audiogram was observed in 40.6% of the participants in at least one ear with 15.4% having bilateral notches, 28.8% LE notches, and 27.1% RE notches. Unilateral 4000 Hz notches were almost twice as prevalent as bilateral 4000 Hz notches. Viewed as a function of age, notched audiograms were most common (∼35% of the participants) in the 40 and 50 yr groups with a diminishing prevalence

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

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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

Planar Ultrawideband Antenna with Photonically Controlled Notched Bands

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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.

Femoral neck-shaft angle in extra-capsular proximal femoral fracture fixation; does it make a TAD of difference?

Science.gov (United States)

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.

Imaging features of anterior cruciate ligament reconstruction graft insufficiency

International Nuclear Information System (INIS)

Shang Yao; Zhang Yue; Tian Chunyan; Zheng Zhuozhao

2011-01-01

Objective: To investigate the imaging features of anterior cruciate ligament (ACL) graft insufficiency. Methods: X-Ray and MR imaging examinations in 24 consecutive patients who had ACL reconstructive graft insufficiency were retrospectively evaluated for tunnel position, osteoarthrosis and its related complications. Follow-up arthroscopy showed 16 graft tears and 8 graft laxities. Fisher exact test was used to compare tunnel malpositions, the proportion of graft tear on MRI and osteoarthrosis between graft tear group and graft laxity group. Results: Two malpositions of tibial tunnel and 3 malpositions of femoral tunnel were seen in graft tear group. Three-malpositions of tibial tunnel and 4 malpositions of femoral tunnel were seen in graft laxity group. The proportion of tibial or femoral malposition showed no significant difference between the two groups (P=0.289, P=0.167). In graft tear group, 15 complete graft tears were diagnosed correctly, 1 partial tear was misdiagnosed as normal on MRI. In graft laxity group, 4 grafts were diagnosed as normal and 4 were considered as graft tear on MRI. A significant difference was seen between the two groups (P=0.028) in the proportion of graft tear diagnosed on MRI. Fourteen osteoarthrosis were seen in graft tear group and 5 in graft laxity group. No significant difference was seen between the two groups (P= 0.289) in the proportion of osteoarthrosis. Conclusion: The proportions of tunnel malposition and osteoarthrosis showed no significant difference between the graft tear group and graft Laxity group. Most graft tears can be diagnosed accurately on MRI, but some cases of graft laxity may be misdiagnosed for graft tear. (authors)

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

International Nuclear Information System (INIS)

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)

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

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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

Electroacupuncture pretreatment induces tolerance against focal cerebral ischemia through activation of canonical Notch pathway

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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.

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

International Nuclear Information System (INIS)

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)

Notch activation is dispensable for D, L-sulforaphane-mediated inhibition of human prostate cancer cell migration.

Directory of Open Access Journals (Sweden)

Eun-Ryeong Hahm

Full Text Available D, L-Sulforaphane (SFN, a synthetic racemic analog of broccoli constituent L-sulforaphane, is a highly promising cancer chemopreventive agent with in vivo efficacy against chemically-induced as well as oncogene-driven cancer in preclinical rodent models. Cancer chemopreventive effect of SFN is characterized by G(2/M phase cell cycle arrest, apoptosis induction, and inhibition of cell migration and invasion. Moreover, SFN inhibits multiple oncogenic signaling pathways often hyperactive in human cancers, including nuclear factor-κB, Akt, signal transducer and activator of transcription 3, and androgen receptor. The present study was designed to determine the role of Notch signaling, which is constitutively active in many human cancers, in anticancer effects of SFN using prostate cancer cells as a model. Exposure of human prostate cancer cells (PC-3, LNCaP, and/or LNCaP-C4-2B to SFN as well as its naturally-occurring thio-, sulfinyl-, and sulfonyl-analogs resulted in cleavage (activation of Notch1, Notch2, and Notch4, which was accompanied by a decrease in levels of full-length Notch forms especially at the 16- and 24-hour time points. The SFN-mediated cleavage of Notch isoforms was associated with its transcriptional activation as evidenced by RBP-Jk-, HES-1A/B- and HEY-1 luciferase reporter assays. Migration of PC-3 and LNCaP cells was decreased significantly by RNA interference of Notch1 and Notch2, but not Notch4. Furthermore, SFN-mediated inhibition of PC-3 and LNCaP cell migration was only marginally affected by knockdown of Notch1 and Notch2. Strikingly, SFN administration to Transgenic Adenocarcinoma of Mouse Prostate transgenic mice failed to increase levels of cleaved Notch1, cleaved Notch2, and HES-1 proteins in vivo in prostatic intraepithelial neoplasia, well-differentiated carcinoma or poorly-differentiated prostate cancer lesions. These results indicate that Notch activation is largely dispensable for SFN-mediated inhibition of cell

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

Science.gov (United States)

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

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

Science.gov (United States)

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.

Critical applied stresses for a crack initiation from a sharp V-notch

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L. Náhlík

2014-10-01

Full Text Available The aim of the paper is to estimate a value of the critical applied stress for a crack initiation from a sharp V-notch tip. The classical approach of the linear elastic fracture mechanics (LELM was generalized, because the stress singularity exponent differs from 0.5 in the studied case. The value of the stress singularity exponent depends on the V-notch opening angle. The finite element method was used for a determination of stress distribution in the vicinity of the sharp V-notch tip and for the estimation of the generalized stress intensity factor depending on the V-notch opening angle. Critical value of the generalized stress intensity factor was obtained using stability criteria based on the opening stress component averaged over a critical distance d from the V-notch tip and generalized strain energy density factor. Calculated values of the critical applied stresses were compared with experimental data from the literature and applicability of the LEFM concept is discussed.

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

Directory of Open Access Journals (Sweden)

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.

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

DEFF Research Database (Denmark)

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....

Metabolic syndrome impairs notch signaling and promotes apoptosis in chronically ischemic myocardium.

Science.gov (United States)

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.

Prognostic value of Notch-1 expression in hepatocellular carcinoma: a meta-analysis

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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

Damage Study in Notched Particulate Composie Specimens Under Nonuniform Strain Loading

National Research Council Canada - National Science Library

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...

Femoral neck buttressing: a radiographic and histologic analysis

International Nuclear Information System (INIS)

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.)

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

International Nuclear Information System (INIS)

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

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

DEFF Research Database (Denmark)

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...

Risk stratification for avascular necrosis of the femoral head after internal fixation of femoral neck fractures by post-operative SPECT/CT

Energy Technology Data Exchange (ETDEWEB)

Han, Sang Won; Oh, Min Young; Yoon, Seok Ho; Kim, Jin Soo; Chang, Jae Suk; Ryu, Jin Sook [Asan Medical CenterUniversity of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Ji Wan [Dept. of Orthopedic Surgery, Haeundae Paik Hospital, Inje University, Busan (Korea, Republic of)

2017-03-15

Avascular necrosis (AVN) of the femoral head is a major complication after internal fixation of a femoral neck fracture and determines the functional prognosis. We investigated postoperative bone single-photon emission computed tomography/computed tomography (SPECT/CT) for assessing the risk of femoral head AVN. We retrospectively reviewed 53 consecutive patients who underwent bone SPECT/CT within 2 weeks of internal fixation of a femoral neck fracture and follow-up serial hip radiographs over at least 12 months. Nine patients developed femoral head AVN. In 15 patients who showed normal uptake on immediate postoperative SPECT/CT, no AVN occurred, whereas 9 of 38 patients who showed cold defects of the femoral head later developed AVN. The negative predictive value of immediate postoperative SPECT/CT for AVN was 100 %, whereas the positive predictive value was 24 %. Among 38 patients with cold defects, 1 developed AVN 3 months postoperatively. A follow-up bone SPECT/CT was performed in the other 37 patients at 2–10 months postoperatively. The follow-up bone SPECT/CT revealed completely normalized femoral head uptake in 27, partially normalized uptake in 8, and persistent cold defects in 2 patients. AVN developed in 3.7 % (1/27), 62.5 % (5/8), and 100 % (2/2) of each group, respectively. According to the time point of imaging, radiotracer uptake patterns of the femoral head on postoperative bone SPECT/CT indicate the risk of AVN after internal fixation of femoral neck fractures differently. Postoperative bone SPECT/CT may help orthopedic surgeons determine the appropriate follow-up of these patients.

Risk stratification for avascular necrosis of the femoral head after internal fixation of femoral neck fractures by post-operative SPECT/CT

International Nuclear Information System (INIS)

Han, Sang Won; Oh, Min Young; Yoon, Seok Ho; Kim, Jin Soo; Chang, Jae Suk; Ryu, Jin Sook; Kim, Ji Wan

2017-01-01

Avascular necrosis (AVN) of the femoral head is a major complication after internal fixation of a femoral neck fracture and determines the functional prognosis. We investigated postoperative bone single-photon emission computed tomography/computed tomography (SPECT/CT) for assessing the risk of femoral head AVN. We retrospectively reviewed 53 consecutive patients who underwent bone SPECT/CT within 2 weeks of internal fixation of a femoral neck fracture and follow-up serial hip radiographs over at least 12 months. Nine patients developed femoral head AVN. In 15 patients who showed normal uptake on immediate postoperative SPECT/CT, no AVN occurred, whereas 9 of 38 patients who showed cold defects of the femoral head later developed AVN. The negative predictive value of immediate postoperative SPECT/CT for AVN was 100 %, whereas the positive predictive value was 24 %. Among 38 patients with cold defects, 1 developed AVN 3 months postoperatively. A follow-up bone SPECT/CT was performed in the other 37 patients at 2–10 months postoperatively. The follow-up bone SPECT/CT revealed completely normalized femoral head uptake in 27, partially normalized uptake in 8, and persistent cold defects in 2 patients. AVN developed in 3.7 % (1/27), 62.5 % (5/8), and 100 % (2/2) of each group, respectively. According to the time point of imaging, radiotracer uptake patterns of the femoral head on postoperative bone SPECT/CT indicate the risk of AVN after internal fixation of femoral neck fractures differently. Postoperative bone SPECT/CT may help orthopedic surgeons determine the appropriate follow-up of these patients

Limit load and fully plastic stress analysis for circular notched plates and bars using fully plastic analysis

International Nuclear Information System (INIS)

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

Valsartan ameliorates podocyte loss in diabetic mice through the Notch pathway.

Science.gov (United States)

Gao, Feng; Yao, Min; Cao, Yanping; Liu, Shuxia; Liu, Qingjuan; Duan, Huijun

2016-05-01

The Notch pathway is known to be linked to diabetic nephropathy (DN); however, its underlying mechanism was poorly understood. In the present study, we examined the effect of Valsartan, an angiotensin II type 1 receptor antagonist, on the Notch pathway and podocyte loss in DN. Diabetes was induced in mice by an intraperitoneal injection of streptozotocin and and this was followed by treatment with Valsartan. Levels of blood glucose, kidney weight and body weight, as well as proteinuria were measured. Samples of the kidneys were also histologically examined. The relative levels of Jagged1, Notch1, Notch intracellular domain 1 (NICD1), Hes family BHLH transcription factor 1 (Hes1) and Hes-related family BHLH transcription factor with YRPW motif 1 expression (Hey1) in the glomeruli were determined by immunohistochemical analysis, western blot analysis and RT-qPCR. The B-Cell CLL/Lymphoma 2 (Bcl-2) and p53 pathways were examined by western blot analysis. Apoptosis and detachment of podocytes from the glomerular basement membrane were examined using a TUNEL assay, flow cytometric analysis and ELISA. The number of podocytes was quantified by measuring Wilms tumor-1 (WT-1) staining. We noted that the expression of Jagged1, Notch1, NICD1, Hes1 and Hey1 was increased in a time-dependent manner in the glomeruli of mice with streptozotocin (STZ)-induced diabetes. Moreover, in diabetic mice, Valsartan significantly reduced kidney weight and proteinuria, and mitigated the pathogenic processes in the kidneys. Valsartan also inhibited the activation of Notch, Bcl-2 and p53 pathways and ameliorated podocyte loss in the glomeruli of mice with STZ-induced diabetes. Taken together, these findings indicated that Valsartan exerted a beneficial effect on reducing podocyte loss, which is associated with inhibition of Notch pathway activation in the glomeruli of diabetic mice.

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

Indian Academy of Sciences (India)

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.

Notch signaling regulates expression of Mcl-1 and apoptosis in PPD-treated macrophages.

Science.gov (United States)

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.

Clinical impact of de-regulated Notch-1 and Notch-3 in the development and progression of HPV-associated different histological subtypes of precancerous and cancerous lesions of human uterine cervix.

Science.gov (United States)

Tripathi, Richa; Rath, Gayatri; Jawanjal, Poonam; Sharma, Shweta; Singhal, Pallavi; Bhambhani, Suresh; Hussain, Showket; Bharadwaj, Mausumi

2014-01-01

Cervical cancer is the leading cause of cancer related deaths among women in India. Limited reports are available for Notch-1 and Notch-3 protein in cervical carcinoma, which play crucial role in cell proliferation, differentiation, and apoptosis. This study was designed to evaluate the role of Notch-1 and Notch-3 with context to HPV infection in cervical carcinoma. A total of 168 tissue biopsy samples comprising of tumor specimens (n = 98), precancer (n = 30) and non-neoplastic cervical tissues (n = 40) were screened for HPV infection by PCR and expression of Notch-1 and Notch-3 protein by Immunohistochemistry and Immunoblotting. 80% (24/30) were found to be positive for HPV in precancer and 86.7% (85/98) in cancer patients. Notch-1 expression of precancer and cancer cases was found to be significantly down-regulated with severity of disease in nuclear (3.43±0.29; 2.04±0.19, p = 0.0001, p = 0.0001) and cytoplasm (3.07±0.29; 2.29±0.17, p = 0.0001, p = 0.0001) obtained from different stages as compared to normal cervix tissue (5.40±0.19, 4.97±0.15; pcervix tissue (0.95±0.20, 0.70±0.20; pcancer through the deregulation of Notch signalling. This study also shows the clinical utility of both proteins which may be used as predictable biomarkers in diagnosing different histological sub-types of HPV associated cervical cancer. Nevertheless, abnormal activation of this pathway may provide legitimate targets for cervical cancer therapy.

Second generation γ-secretase modulators exhibit different modulation of Notch β and Aβ production.

Science.gov (United States)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

Ipsilateral femoral neck and shaft fractures: An overlooked association

International Nuclear Information System (INIS)

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)

Ipsilateral femoral neck and shaft fractures: An overlooked association

Energy Technology Data Exchange (ETDEWEB)

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).

Review of evolution of tunnel position in anterior cruciate ligament reconstruction.

Science.gov (United States)

Rayan, Faizal; Nanjayan, Shashi Kumar; Quah, Conal; Ramoutar, Darryl; Konan, Sujith; Haddad, Fares S

2015-03-18

Anterior cruciate ligament (ACL) rupture is one of the commonest knee sport injuries. The annual incidence of the ACL injury is between 100000-200000 in the United States. Worldwide around 400000 ACL reconstructions are performed in a year. The goal of ACL reconstruction is to restore the normal knee anatomy and kinesiology. The tibial and femoral tunnel placements are of primordial importance in achieving this outcome. Other factors that influence successful reconstruction are types of grafts, surgical techniques and rehabilitation programmes. A comprehensive understanding of ACL anatomy has led to the development of newer techniques supplemented by more robust biological and mechanical concepts. In this review we are mainly focussing on the evolution of tunnel placement in ACL reconstruction, focusing on three main categories, i.e., anatomical, biological and clinical outcomes. The importance of tunnel placement in the success of ACL reconstruction is well researched. Definite clinical and functional data is lacking to establish the superiority of the single or double bundle reconstruction technique. While there is a trend towards the use of anteromedial portals for femoral tunnel placement, their clinical superiority over trans-tibial tunnels is yet to be established.

Effects of mineral content on the fracture properties of equine cortical bone in double-notched beams.

Science.gov (United States)

McCormack, Jordan; Stover, Susan M; Gibeling, Jeffery C; Fyhrie, David P

2012-06-01

We recently developed a method to measure cortical bone fracture initiation toughness using a double-notched beam in four-point bending. This method was used to test the hypothesis that mineralization around the two notch roots is correlated with fracture toughness and crack extension (physical damage). Total energy absorbed to failure negatively correlated with average mineralization of the beam (r(2)=0.62), but not with notch root mineralization. Fracture initiation toughness was positively correlated to mineralization at the broken notch root (r(2)=0.34). Crack length extension at the unbroken notch was strongly negatively correlated with the average mineralization of the notch roots (r(2)=0.81) whereas crack length extension at the broken notch did not correlate with any of the mineralization measurements. Mineralization at the notch roots and the average mineralization contributed independently to the mechanical and damage properties. The data are consistent with a hypothesis that a) high notch root mineralization results in less stable crack length extension but high force to initiate unstable crack propagation while b) higher average mineralization leads to low post-yield (and total) energy absorption to failure. Copyright © 2012 Elsevier Inc. All rights reserved.

Ultra-Wideband Notched Characteristic Fed by Coplanar Waveguide

Directory of Open Access Journals (Sweden)

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.

Femoral component rotation in patellofemoral joint replacement.

Science.gov (United States)

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.

Clinical study on 44 cases of femoral hernia

International Nuclear Information System (INIS)

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)

MR evaluation of femoral neck version and tibial torsion

Energy Technology Data Exchange (ETDEWEB)

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.)

Estimations of creep behavior and failure life for a circumferentially notched specimen

International Nuclear Information System (INIS)

Kobayashi, Ken-ichi; Yokobori, Toshimitsu; Kikuchi, Kenji.

1997-01-01

No method with which to characterize and/or illustrate total creep behavior for specimens with notches, holes or cracks has been proposed. In this paper it is proposed that most creep curves can be drawn with a master curve for each creep test whenever test conditions and failure modes are similar to each other, and the lifetime ratio normalized by the rupture time is introduced. Using smooth and circumferentially notched specimens of 2.25 Cr-1 Mo steel, creep tests were performed at 600degC for examination of this concept. Furthermore, a θ projection method was used to describe creep curves for notched specimens and to extrapolate longer creep lives. Then, the whole creep curve shape for notched specimens could be easily drawn, except for that in the vicinity of the rupture point. However, longer creep lives of notched specimens were underestimated in comparison with a simple extrapolation of the experimental data. This resulted from the negative dependence of the parameter of θ 3 on the applied stress. (author)

Correlation between baseline femoral neck marrow status and the development of femoral head osteonecrosis in corticosteroid-treated patients: A longitudinal study by MR imaging

International Nuclear Information System (INIS)

Vande Berg, Bruno C.; Gilon, Raphael; Malghem, Jacques; Lecouvet, Frederic; Depresseux, Genevieve; Houssiau, Frederic A.

2006-01-01

Objective: To test the hypothesis that the development of corticosteroid (CS)-associated femoral head osteonecrosis (ON) is influenced by baseline femoral neck marrow status. Patients and methods: The population consisted of 20 untreated patients with a newly diagnosed rheumatic disease in whom a standardized CS regimen was planned. Before CS treatment, baseline femoral neck marrow status was determined by magnetic resonance (MR) imaging on T1-weighted images (proportion of surface area of femoral neck and intertrochanteric area occupied by fatty marrow; index of marrow conversion [IMC]) and on a quantitative MR sequence (bulk T1 values of femoral head and neck). The presence of ON was assessed by coronal T1-weighted MR images of the hips at 6 and 12 months. Results: None of the patients suffered from ON at baseline. Four patients (20%) developed bilateral femoral head ON at 6 months. The mean percentage of fat marrow in the femoral neck before treatment was significantly higher in ON-positive than in ON-negative patients (p = 0.0025). The mean baseline femoral neck IMC value, which parallels the degree of red to yellow marrow conversion, was higher in ON-positive than in ON-negative patients (p = 0.089). The mean baseline bulk T1 value of the femoral neck (but not of the femoral head), which inversely correlates with the amount of fat marrow, was significantly shorter in ON-positive than in ON-negative patients (p = 0.0298). Conclusion: The development of CS-associated femoral head ON is correlated with a high fat content in the proximal femur before CS therapy

Herniography off femoral, obturator and perineal hernias

International Nuclear Information System (INIS)

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

Notch Signaling and Brain Tumors

DEFF Research Database (Denmark)

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...

Digital notch filter based active damping for LCL filters

DEFF Research Database (Denmark)

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....

Three-dimensional vibrations of cylindrical elastic solids with V-notches and sharp radial cracks

Science.gov (United States)

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

Notch and hydrogen effects on sensitized 21-6-9 stainless steel

International Nuclear Information System (INIS)

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

Thermally induced high frequency random amplitude fatigue damage at sharp notches

International Nuclear Information System (INIS)

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

Nrf2 and Notch Signaling in Lung Cancer: Near the Crossroad

Directory of Open Access Journals (Sweden)

Angelo Sparaneo

2016-01-01

Full Text Available The transcription factor Nrf2 (NF-E2 related factor 2 is a master regulator of the cell antioxidant response associated with tumor growth and resistance to cytotoxic treatments. In particular, Nrf2 induces upregulation of cytoprotective genes by interacting with the closely situated AREs (Antioxidant Response Elements in response to endogenous or exogenous stress stimuli and takes part to several oncogenic signaling pathways. Among these, the crosstalk with Notch pathway has been shown to enhance cytoprotection and maintenance of cellular homeostasis, tissue organization by modulating cell proliferation kinetics, and stem cell self-renewal in several organs. The role of Notch and Nrf2 related pathways in tumorigenesis is highly variable and when they are both abnormally activated they can synergistically cause neoplastic proliferation by promoting cell survival, differentiation, invasion, and metastases. NFE2L2, KEAP1, and NOTCH genes family appear in the list of significantly mutated genes in tumors in both combined and individual sets, supporting the crucial role that the aberrant Nrf2-Notch crosstalk might have in cancerogenesis. In this review, we summarize current knowledge about the alterations of Nrf2 and Notch pathways and their reciprocal transcriptional regulation throughout tumorigenesis and progression of lung tumors, supporting the potentiality of putative biomarkers and therapeutic targets.

Mechano sorptive behaviour of notched beams in bending

DEFF Research Database (Denmark)

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...

Trochanteric entry femoral nails yield better femoral version and lower revision rates-A large cohort multivariate regression analysis.

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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.

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

International Nuclear Information System (INIS)

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)

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

Energy Technology Data Exchange (ETDEWEB)

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.

Constitutively active Notch1 induces growth arrest of HPV-positive cervical cancer cells via separate signaling pathways

International Nuclear Information System (INIS)

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

Evidence of Aortopathy in Mice with Haploinsufficiency of Notch1 in Nos3-Null Background

Directory of Open Access Journals (Sweden)

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.

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

International Nuclear Information System (INIS)

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)

Bilateral femoral neck fractures following pelvic irradiation

International Nuclear Information System (INIS)

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.)

“Table-less” and “Assistant-less” Direct Anterior Approach to Hip Arthroplasty

Directory of Open Access Journals (Sweden)

Daniel C Allison

2015-10-01

Full Text Available In recent years, specialized, non-sterile, traction table systems have facilitated Direct Anterior Approach (DAA hip arthroplasty. To combat the potential downsides of these traction systems, a sterile, intra-operative retractor option has emerged as a means to access the surgical site more easily, minimize soft-tissue trauma, and reduce the degree of required human assistance. This chapter describes the setup, surgical approach, and early results of a retractor system (the Phantom MIS Anterior Hip Retractor system [TeDan Surgical Innovations, Inc. {TSI}, Houston, Texas, US Patent # 8,808,176 B2], which uses a standard operating table, allows preparation of both lower extremities free in the surgical field, is compatible with fluoroscopy, and aids in both acetabular and femoral exposure, preparation, and implantation. Early outcome data indicates that this system significantly minimizes the need for surgical assistance, while allowing for safe and effective DAA performance, facilitating the procedure for high-volume surgeons and shortening the learning curve for surgeons new to the procedure.

Falso Aneurisma Femoral Iatrogénico: Ainda uma indicação para a Cirurgia Convencional? Iatrogenic femoral pseudoaneurysm: still an indication for conventional surgery?

Directory of Open Access Journals (Sweden)

Nelson Oliveira

2011-12-01

Full Text Available Introdução: Os Falsos Aneurismas (FA são uma das complicações mais frequentemente associadas à punção femoral diagnóstica e de intervenção cardíaca. A sua abordagem terapêutica tem evoluído no sentido da preponderância das técnicas não invasivas sendo a Cirurgia Convencional cada vez menos frequentemente praticada. Objectivos: Os autores propõem a propósito de um caso clínico, e através de uma revisão da literatura discutir a abordagem terapêutica dos FA e as indicações da Cirurgia Convencional. Caso clínico: Doente de sessenta e um anos, sexo masculino, com antecedentes de hipertensão arterial, doença coronária com enfarte agudo do miocárdio prévio, miocardiopatia dilatada, fibrilhação auricular paroxística sendo portador de cardiodesfibrilhador. Foi submetido a cateterismo cardíaco por via femoral direita para ablação do Feixe de His, tendo sido referenciado ao Serviço de Angiologia e Cirurgia Vascular por desenvolvimento progressivo de massa pulsátil dolorosa acompanhada de hipostesia da face anterior da coxa. A Angiodinografia confirmou a presença de falso aneurisma da artéria femoral profunda direita com 3cm de maior diâmetro e a presença de uma fístula entre a artéria e a veia femorais superficiais direitas. Por abordagem cirúrgica aberta, foi realizada a exclusão do falso aneurisma e rafia da artéria e veia femorais superficiais. Conclusão: A abordagem de primeira linha dos falsos aneurismas iatrogénicos pós cateterismo cardíaco é não invasiva mas a Cirurgia Convencional detém ainda um lugar primordial para um grupo restrito de doentes.Introduction: Pseudoaneurysms (PAN are one of the most common complications of cardiac catheterization. Treatment has evolved towards a less invasive approach, reducing the number of Open repairs. Objectives: The authors propose to discuss the contemporary management of PAN and the remaining indications for Conventional Surgical Repair based upon a case

Constitutively active Notch1 converts cranial neural crest-derived frontonasal mesenchyme to perivascular cells in vivo

Directory of Open Access Journals (Sweden)

Sophie R. Miller

2017-03-01

Full Text Available Perivascular/mural cells originate from either the mesoderm or the cranial neural crest. Regardless of their origin, Notch signalling is necessary for their formation. Furthermore, in both chicken and mouse, constitutive Notch1 activation (via expression of the Notch1 intracellular domain is sufficient in vivo to convert trunk mesoderm-derived somite cells to perivascular cells, at the expense of skeletal muscle. In experiments originally designed to investigate the effect of premature Notch1 activation on the development of neural crest-derived olfactory ensheathing glial cells (OECs, we used in ovo electroporation to insert a tetracycline-inducible NotchΔE construct (encoding a constitutively active mutant of mouse Notch1 into the genome of chicken cranial neural crest cell precursors, and activated NotchΔE expression by doxycycline injection at embryonic day 4. NotchΔE-targeted cells formed perivascular cells within the frontonasal mesenchyme, and expressed a perivascular marker on the olfactory nerve. Hence, constitutively activating Notch1 is sufficient in vivo to drive not only somite cells, but also neural crest-derived frontonasal mesenchyme and perhaps developing OECs, to a perivascular cell fate. These results also highlight the plasticity of neural crest-derived mesenchyme and glia.

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

Science.gov (United States)

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.

Magnetic resonance imaging of the femoral head necrosis

Energy Technology Data Exchange (ETDEWEB)

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.

Magnetic resonance imaging of the femoral head necrosis

International Nuclear Information System (INIS)

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)

Fibre Optic Notch Filter For The Antiproton Decelerator Stochastic Cooling System

CERN Document Server

Simmonds, Max Vincent John

2016-01-01

The project scope included reverse engineering, upgrading, and recovering the operational conditions of an existing fibre optic notch filter. Once operational, tests were to be preformed to confirm the performance of the temperature stabilisation. The end goal is to use said notch filter in the Antiproton Decelerator (AD) facility at CERN to help aid antimatter research. The notch filter was successfully reverse engineered and then documented. Changes were made in order to increase performance and reliability, and also allow easy integration into the AD. An additional phase was added whereby the notch filter was to be controller via a touchscreen computer, situated next to the filter, allowing engineers to set-up each of the electronic devices used. While one of the devices (Motorised Delay Line) can be controlled by the touchscreen computer, the other two cannot.Due to time constraints and difficulties with the Beckhoff TwincatII programming language, the USB devices were not able to be controlled via the To...

Femoral component loosening after hip resurfacing arthroplasty

International Nuclear Information System (INIS)

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

Notch signaling in embryology and cancer

National Research Council Canada - National Science Library

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...

Conditions for crack initiation in an orthotropic bi-material notch

Czech Academy of Sciences Publication Activity Database

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

Avascular necrosis of the femoral head

International Nuclear Information System (INIS)

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)

On the notch ductility of a magnesium-rare earth alloy

Energy Technology Data Exchange (ETDEWEB)

Kondori, B., E-mail: bkondori.13034@tamu.edu [Department of Materials Science & Engineering, Texas A& M University, College Station, TX 77843 (United States); Benzerga, A.A. [Department of Materials Science & Engineering, Texas A& M University, College Station, TX 77843 (United States); Department of Aerospace Engineering, Texas A& M University, College Station, TX 77843 (United States)

2015-10-28

The room-temperature notch ductility of magnesium-rare earth alloy WE43 is investigated for two loading orientations. This material is endowed with quasi-isotropic plastic flow properties, higher strength and similar uniaxial ductility in comparison with other commercially available Mg alloys. The authors have recently shown that the notch ductility of a Mg–Al–Zn alloy is greater than its uniaxial ductility over a wide range of notch geometries. This paper investigates whether the same trends hold for WE43, discusses the orientation dependence of ductility and the propensity for intergranular fracture at high levels of hydrostatic tension. The latter mode of fracture is analyzed by means of detailed fractography in order to elucidate the role of grain-boundary particles and precipitates in the fracture process.

CT study of avascular necrosis of femoral head in adults

International Nuclear Information System (INIS)

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

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

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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

Automated 3D quantitative assessment and measurement of alpha angles from the femoral head-neck junction using MR imaging

International Nuclear Information System (INIS)

Xia, Ying; Chandra, Shekhar S; Crozier, Stuart; Fripp, Jurgen; Walker, Duncan; Engstrom, Craig

2015-01-01

To develop an automated approach for 3D quantitative assessment and measurement of alpha angles from the femoral head-neck (FHN) junction using bone models derived from magnetic resonance (MR) images of the hip joint.Bilateral MR images of the hip joints were acquired from 30 male volunteers (healthy active individuals and high-performance athletes, aged 18–49 years) using a water-excited 3D dual echo steady state (DESS) sequence. In a subset of these subjects (18 water-polo players), additional True Fast Imaging with Steady-state Precession (TrueFISP) images were acquired from the right hip joint. For both MR image sets, an active shape model based algorithm was used to generate automated 3D bone reconstructions of the proximal femur. Subsequently, a local coordinate system of the femur was constructed to compute a 2D shape map to project femoral head sphericity for calculation of alpha angles around the FHN junction. To evaluate automated alpha angle measures, manual analyses were performed on anterosuperior and anterior radial MR slices from the FHN junction that were automatically reformatted using the constructed coordinate system.High intra- and inter-rater reliability (intra-class correlation coefficients  >  0.95) was found for manual alpha angle measurements from the auto-extracted anterosuperior and anterior radial slices. Strong correlations were observed between manual and automatic measures of alpha angles for anterosuperior (r  =  0.84) and anterior (r  =  0.92) FHN positions. For matched DESS and TrueFISP images, there were no significant differences between automated alpha angle measures obtained from the upper anterior quadrant of the FHN junction (two-way repeated measures ANOVA, F  <  0.01, p  =  0.98).Our automatic 3D method analysed MR images of the hip joints to generate alpha angle measures around the FHN junction circumference with very good reliability and reproducibility. This work has the

Experimental and Numerical Analysis of Notched Composites Under Tension Loading

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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

The Advanced Glaucoma Intervention Study (AGIS): 10. Variability among academic glaucoma subspecialists in assessing optic disc notching.

Science.gov (United States)

Gaasterland, D E; Blackwell, B; Dally, L G; Caprioli, J; Katz, L J; Ederer, F

2001-01-01

An analysis of data from the Advanced Glaucoma Intervention Study (AGIS) has found eyes reported to have partial optic disc rim notching (not to the edge) at baseline to have less risk of subsequent visual field loss than eyes with no notching. Because this is counterintuitive and because classification of notching had not been defined in the AGIS protocol, we have assessed AGIS ophthalmologists interobserver and intraobserver agreement on notching. Fourteen glaucoma subspecialists classified notching in 26 pairs of stereoscopic disc photographs of eyes with mild to severe glaucomatous optic neuropathy. They classified images as showing either no notching, notching not to the edge, or notching to the edge. Several hours later, 10 of them classified the same images a second time. In an analysis of interobserver agreement, of 26 stereoscopic images, a plurality of ophthalmologists classified notching as absent in 9 (35%), as present but not to the edge in 7 (27%), and as present and not to the edge in 10 (38%). All 14 ophthalmologists (100%) agreed on the classification of 7 (27%) of the images, and 13 of the 14 ophthalmologists (93%) agreed on the classification of 4 additional images (15%). Of these 11 images with at least 93% agreement, notching was reported as absent in 3 (27%) and to the edge in 8 (73%). In the remaining 15 images, there was substantial disagreement about whether notching was present and, if so, whether it was to the edge. In an analysis of intraobserver agreement, none of the 10 ophthalmologists who completed the viewing a second time classified all eyes exactly the same as the first time, though 5 ophthalmologists made 4 or fewer reclassifications. Overall, 80% of the original classifications were reproduced on second reading. Of the initial classifications that were not reproduced, slightly more than half were first classified as having notching not to the edge. Without definitions or examples of optic disc rim notching, the glaucoma

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