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PubMed2000

Influence of ceramic and stainless steel brackets on the notching of archwires during clinical treatment.

The surface topography of 100 clinically used archwires of stainless steel, beta-, or nickel-titanium were investigated that had contacted either ceramic or stainless steel brackets. One group consisted of two sets: 60 wires with no treatment records accessed to bias analyses, and 40 wires for which extensive clinical records were available, half of which were used with ceramic or stainless steel brackets. A control group consisted of two sets: 30 unused wires comprised of five round and rectangular wires of each alloy, and four wires that were ligated and immediately removed from patients' mouths. After ultrasonic cleaning, each wire was inspected under an optical and/or a scanning electron microscope. Notches were categorized with regard to frequency, patterns, and severity, and mapped as a function of wire aspect (lingual, facial, and occlusal/gingival) and anatomical regions (molar, premolar, canine, and incisor). From these data the average severity of notch patterns and a notching index were derived. Although no recognizable defect patterns were observed in the control group, seven basic patterns were recognized for each wire cross-sectional shape in the clinically used wires. These wires appeared most damaged on their lingual aspect and least damaged on their facial aspect. With regard to anatomical regions, notching was prevalent in the anterior regions and sparse in the molar regions. The notch activity and the severity were nearly three times greater from ceramic brackets than from stainless steel brackets. Over one-third of all notches documented in ceramic bracket cases had severity numbers of 3 and penetrated at least one-quarter of each wire's dimension, However, over two-thirds of all notches documented in stainless steel bracket cases had severity numbers of 1. From these tabulations a theory of notch formation was proposed in which vertical movement from tooth or wire during mastication caused fretting wear, and horizontal movement during orthodontic procedures such as space closure, tipping, or bodily movement caused sliding wear.

Ceramics↗
PubMed2003

Notch-induced E2A ubiquitination and degradation are controlled by MAP kinase activities.

Notch signals are important for lymphocyte development but downstream events that follow Notch signaling are not well understood. Here, we report that signaling through Notch modulates the turnover of E2A proteins including E12 and E47, which are basic helix-loop-helix proteins crucial for B and T lymphocyte development. Notch-induced degradation requires phosphorylation of E47 by p42/p44 MAP kinases. Expression of the intracellular domain of Notch1 (N1-IC) enhances the association of E47 with the SCF(Skp2) E3 ubiquitin ligase and ubiquitination of E47, followed by proteasome-mediated degradation. Furthermore, N1-IC induces E2A degradation in B and T cells in the presence of activated MAP kinases. Activation of endogenous Notch receptors by treatment of splenocytes with anti-IgM or anti-CD3 plus anti-CD28 also leads to E2A degradation, which is blocked by the inhibitors of Notch activation or proteasome function. Notch-induced E2A degradation depends on the function of its downstream effector, RBP-Jkappa, probably to activate target genes involved in the ubiquitination of E2A proteins. Thus we propose that Notch regulates lymphocyte differentiation by controlling E2A protein turnover.

Animals↗
PubMed1992

A genetic analysis of deltex and its interaction with the Notch locus in Drosophila melanogaster.

During Drosophila development networks of genes control the developmental pathways that specify cell fates. The Notch gene is a well characterized member of some cell fate pathways, and several other genes belonging to these same pathways have been identified because they share a neurogenic null phenotype with Notch. However, it is unlikely that the neurogenic genes represent all of the genes in these pathways. The goal of this research was to use a genetic approach to identify and characterize one of the other genes that acts with Notch to specify cell fate. Mutant alleles of genes in the same pathway should have phenotypes similar to Notch alleles and should show phenotypic interactions with Notch alleles. With this approach we identified the deltex gene as a potential cell fate gene. An extensive phenotypic characterization of loss-of-function deltex phenotypes showed abnormalities (such as thick wing veins, double bristles and extra cone cells) that suggest that deltex is involved in cell fate decision processes. Phenotypic interactions between deltex and Notch as seen in double mutants showed that Notch and deltex do not code for duplicate functions and that the two genes function together in many different developing tissues. The results of these investigations lead to the conclusion that the deltex gene functions with the Notch gene in one or more developmental pathways to specify cell fate.

Animals↗
PubMed2001

Notch signaling in leukemia.

Mammalian Notch homologs were first identified from the involvement of Notch1 in a recurrent chromosomal translocation in a subset of human T-cell leukemias. The effect of the translocation was twofold: Notch expression was placed under the control of a T-cell-specific element, and Notch was truncated, resulting in a constitutively active protein. Subsequent work has shown that Notch1 is required for T cell commitment and is exclusively oncotropic for T cells. During the past year, several murine models have been used to dissect the function of Notch signaling in lymphoid development and leukemia. These models show that Notch1 drives the earliest stages of T cell commitment and that Notch signaling must be downregulated by the double positive stage for proper T cell development to occur. Constitutive Notch signaling mediated by Notch1, Notch2, or Notch3 predisposes to T-cell leukemia. Future studies are expected to elucidate the mechanisms by which Notch leads to transformation. Identification of the transcriptional targets of Notch signaling is likely to yield important insights.

Animals↗
PubMed1989

Notch is required for successive cell decisions in the developing Drosophila retina.

Mutations in the Notch locus affect a variety of developmental decisions in Drosophila. In this paper, we examine the role of Notch in the developing retina. We reduced Notch activity at successive intervals during development of the retina, and then examined the effect on individual cells. When Notch activity was reduced, cells responded by selecting inappropriate developmental pathways. We found that all cell types appear to require Notch when establishing their fate. To examine further Notch's role in eye development, we examined two alleles of Notch--split and facet-glossy. split flies show defects in the initial clustering of photoreceptors, whereas the defects in facet-glossy flies are due to the misrouting of presumptive primary pigment cells into the secondary pigment cell pathway. Our results suggest that Notch plays a permissive role in the cell-cell interactions used to assemble the eye.

Alleles↗
PubMed1990

The Notch locus and the genetic circuitry involved in early Drosophila neurogenesis.

The genetic and molecular analysis of the Notch locus, which codes for a transmembrane protein sharing homology with the mammalian epidermal growth factor, suggests that the Notch protein is involved in a cell interaction mechanism essential for the differentiation of the embryonic nervous system of Drosophila. Taking advantage of the negative complementation between two Notch mutations that affect the extracellular domain of the protein, we have tried to dissect the genetic circuitry in which Notch is integrated by searching for genes whose products may interact with the Notch protein. This genetic screen has led to the identification of a surprisingly restricted set of interacting loci, including Delta and mastermind. Like Notch, both of these genes belong to a group of loci, the neurogenic loci, which have been previously identified by virtue of their similar mutant phenotype affecting early neurogenesis. We extend these studies by systematically exploring interactions between specific mutations in the Notch molecule and the other neurogenic genes. Furthermore, we show that the molecular lesions of two Notch alleles (nd and nd2), which interact dramatically with mastermind mutations, as well as with a mutation affecting the transducin homologous product of the neurogenic locus Enhancer of split, involve changes in the intracellular domain of the protein.

Alleles↗
PubMed1996

Peak systolic over protodiastolic ratio as an objective substitute for the uterine artery notch.

OBJECTIVE: To measure the inter-rater agreement for the identification of a uterine artery notch, as well as the association between an observed notch and the peak systolic over protodiastolic (A/C) ratio. DESIGN: Cohort study. SETTING: Tertiary care university hospital. POPULATION AND METHODS: Six hundred and sixty-five nulliparous women in whom 1022 examinations of uterine artery velocity waveforms were performed by pulsed Doppler at 18 and at 26 weeks of gestation. Agreement between two independent raters was analysed using Cohen's kappa statistics. A/C ratios of flow velocity waveforms with or without a notch were compared. The agreement between A/C values and the presence of a notch was estimated by measuring the surface under the receiver operating characteristic (ROC) curve. RESULTS: Inter-rater agreement for the identification of a notch was 0.74 (95% CI 0.64-0.83) at 18 weeks and 0.72 (95% CI 0.64-0.80) at 26 weeks. A/C ratios were higher when a notch was present (P < 0.0001). The area under the ROC curve was 0.86 (95% CI 0.81-0.91) for the placental uterine artery and 0.93 (95% CI 0.90-0.96) for the nonplacental artery. An A/C value > or = 2.5 in any uterine artery had a sensitivity of 88% and a specificity of 86% to detect a notch. CONCLUSION: Although there is no definitive definition of the notch, its detection is reproducible within a center. However, published prevalences between centers in unselected populations vary. The measure of the A/C ratio can serve as an objective substitute.

Adult↗
PubMed2005

Use of a skin-fat composite graft to prevent alar notching: an alternative to delayed postoperative repair.

BACKGROUND: Full-thickness defects of the alar rim can be challenging to repair and often require the use of multistaged interpolated flaps. Alar notching is a known complication of these procedures even after cartilage batten grafts have been placed to support the alar framework. Standard techniques for repair of alar notching involve reinsertion of a cartilage graft, usually at the time of alar groove reconstruction 3 months postoperatively. OBJECTIVE: We present a technique to prevent alar notching associated with nasolabial interpolation flaps. If early notching is noted at the time of pedicle division, preemptive placement of a skin-fat composite graft can obviate the need for additional procedures. METHODS: A case report detailing the procedure and a review of the options for repair of alar notching are provided. RESULTS. Placement of a skin-fat composite graft harvested from the divided pedicle flap resulted in correction of alar notching. CONCLUSION: This procedure is presented as an alternative to delayed cartilage grafting for repair of alar rim notching after placement of an interpolated pedicle flap. If notching is noted early, correction at the time of pedicle division allows for use of available tissue for composite grafting, avoidance of a delayed reconstructive procedure, and a good functional and cosmetic

Adipose Tissue↗
PubMed2001

Audiometric notch as a sign of noise induced hearing loss.

OBJECTIVES: To investigate the relation between different types of exposure to noise and a classic sign of noise induced hearing loss (NIHL), the audiometric notch. METHODS: The study sample had exposure to both continuous and impulse noise and was drawn from a population of electrical transmission workers. Audiograms, taken as part of a hearing conservation programme, were read by three clinicians experienced in the assessment of NIHL. Working independently and using their clinical judgment, they were asked to identify localised increases in the threshold of hearing (audiometric notches) which they would attribute to noise, had a suitable history of exposure been elicited. Prevalent cases of NIHL were identified by the presence of a notch in either ear. Risk factors for NIHL were assessed by a questionnaire which sought information about exposure to air blast circuit breaker noise; firearms; explosions, and continuous noise. The odds of exposure to these factors in those with and without hearing loss were calculated, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression. RESULTS: Of the 648 questionnaires sent out 357 were returned, a response rate of 55%. Of these, at least two out of the three assessors identified 175 (49%) people with a notch at any audiometric frequency. There was no association between these cases and the NIHL risk factors identified by the questionnaire, but a further frequency specific analysis showed a small proportion of people (15 (4%)) with notches at 4 kHz who had the expected associations with exposure to noise and a significant OR for firearms of 4.25 (95% CI 1.28 to 14.1). The much larger proportion of people with 6 kHz notches (110 (31%)) did not show these associations. CONCLUSIONS: To diagnose NIHL it is important to elicit a detailed and accurate history of exposure to noise: although the notch at 4 kHz is a well established clinical sign and may be valuable in confirming the diagnosis, the 6 kHz notch is variable and of limited importance.

Audiometry↗
PubMedDate not supplied

Expression failure of the notch signaling system is associated with the pathogenesis of testicular germ cell tumor.

OBJECTIVES: The expression of Notch 1 and its ligand Jagged 2, critical factors in cell type specification, in testicular germ cell tumors was examined in order to evaluate its possible relationship with their pathogenesis. METHODS: Northern blot analysis and immunohistochemical staining for Notch 1 and Jagged 2 were done in 139 samples of testicular germ cell tumors. RESULTS: Notch 1 and Jagged 2 transcripts were expressed in noncancerous testicular tissues and Notch 1 and Jagged 2 proteins were positive in the spermatids. However, the expressions of transcript and protein were negative for both Jagged 2 and Notch 1 in seminomas, they were negative for Jagged 2 but were positive for Notch 1 in embryonal carcinomas and choriocarcinomas, and they were positive for Jagged 2 and Notch 1 in teratomas. CONCLUSIONS: Our results offer, for the first time, the possibility that the activity of the Notch signaling system, one of the cell proliferation and differentiation pathways, correlates with the different histological subtypes of germ cell tumor, which may be responsible for characteristics of cancer cells such as responses to chemotherapy and/or irradiation.

Blotting, Northern↗
PubMed2005

Cyclic strain inhibits Notch receptor signaling in vascular smooth muscle cells in vitro.

Notch signaling has been shown recently to regulate vascular cell fate in adult cells. By applying a uniform equibiaxial cyclic strain to vascular smooth muscle cells (SMCs), we investigated the role of strain in modulating Notch-mediated growth of SMCs in vitro. Rat SMCs cultured under conditions of defined equibiaxial cyclic strain (0% to 15% stretch; 60 cycles/min; 0 to 24 hours) exhibited a significant temporal and force-dependent reduction in Notch 3 receptor expression, concomitant with a significant reduction in Epstein Barr virus latency C promoter-binding factor-1/recombination signal-binding protein of the Jkappa immunoglobulin gene-dependent Notch target gene promoter activity and mRNA levels when compared with unstrained controls. The decrease in Notch signaling was Gi-protein- and mitogen-activated protein kinase-dependent. In parallel cultures, cyclic strain inhibited SMC proliferation (cell number and proliferating cell nuclear antigen expression) while significantly promoting SMC apoptosis (annexin V binding, caspase-3 activity and bax/bcl-x(L) ratio). Notch 3 receptor overexpression significantly reversed the strain-induced changes in SMC proliferation and apoptosis to levels comparable to unstrained control cells, whereas Notch inhibition further potentiated the changes in SMC apoptosis and proliferation. These findings suggest that cyclic strain inhibits SMC growth while enhancing SMC apoptosis, in part, through regulation of Notch receptor and downstream target gene expression.

Animals↗
PubMed2005

Sex-based differences in the anthropometric characteristics of the anterior cruciate ligament and its relation to intercondylar notch geometry: a cadaveric study.

BACKGROUND: A significantly higher rate of anterior cruciate ligament injuries occurs in women involved in sports activities compared to the corresponding male population. Reasons for this disparity are not well understood; however, sex-based differences in the geometry of the anterior cruciate ligament, its morphologic characteristics, and the intercondylar notch size have been cited as possible factors. HYPOTHESES: (1) The anterior cruciate ligament in women has a shorter length, and smaller cross-sectional area and volume than that in men. (2) The female anterior cruciate ligament has a lower mass density. (3) Ligament size is proportional to notch width in both male and female populations. STUDY DESIGN: Descriptive laboratory study. METHODS: Using a 3-dimensional imaging system, the authors measured the geometric parameters, including length, area, and volume, of the anterior cruciate ligaments of 10 male and 10 female donors (all Caucasian). A digital image of the frontal plane of the knee flexed at 90 degrees was used to measure notch size. After the ligament's removal from its attachment sites, its mass was measured using a digital balance. Geometric parameters, mass density, and notch size were compared based on sex. Correlation analyses between ligament size and body anthropometric characteristics, and between notch size and ligament size were performed. RESULTS: The anterior cruciate ligament in women was smaller in length, cross-sectional area, volume, and mass when compared to that in men. No significant difference in ligament mass density was found between the sexes. Also, no differences were found in notch geometry between male and female populations. A correlation between notch size and ligament size was found for men but not for women. CONCLUSIONS: Because the densities of female and male anterior cruciate ligaments appear to be similar, the smaller ligament size in women may contribute to their having a higher rate of ligament injuries. Anterior cruciate ligament size increases in proportion to notch width in men but not in women.

Adolescent↗
PubMed2003

Notch 1 impairs osteoblastic cell differentiation.

Notch receptors are single pass transmembrane receptors activated by membrane-bound ligands with a role in cell proliferation and differentiation. As Notch 1 and 2 mRNAs are expressed by osteoblasts and induced by cortisol, we postulated that Notch could regulate osteoblastogenesis. We investigated the effects of retroviral vectors directing the constitutive expression of the Notch 1 intracellular domain (NotchIC) in murine ST-2 stromal and in MC3T3 cells. NotchIC overexpression was documented by increased Notch 1 transcripts and activity of the Notch-dependent Hairy Enhancer of Split promoter. In the presence of bone morphogenetic protein-2 (BMP-2), ST-2 cells differentiated toward osteoblasts forming mineralized nodules, and Notch 1 opposed this effect and decreased the expression of osteocalcin, type I collagen, and alkaline phosphatase transcripts and Delta2Delta FosB protein. Further, NotchIC decreased Wnt/beta-catenin signaling. As cells differentiated in the presence of BMP-2, they underwent apoptosis, and Notch opposed this event. In the presence of cortisol, NotchIC induced the formation of mature adipocytes and enhanced the effect of cortisol on adipsin, peroxisome proliferator-activated receptor-gamma2 and CCAAT enhancer binding protein alpha and delta mRNA levels. NotchIC also opposed MC3T3 cell differentiation and the expression of a mature osteoblastic phenotype. In conclusion, NotchIC impairs osteoblast differentiation and enhances adipogenesis in stromal cell cultures.

3T3 Cells↗
PubMed2002

Doppler sonography of uterine arteries at 20-23 weeks: risk assessment of adverse pregnancy outcome by quantification of impedance and notch.

OBJECTIVE: To assess the diagnostic value of Doppler sonography of the uterine arteries (DSUA) at 20-23 gestational weeks as screening procedure in a low risk population. PATIENTS AND METHODS: The study group consisted of 7508 singleton low-risk pregnancies. Doppler sonography of both uterine arteries was performed as routine part of anomaly scan. Impedance of both uterine arteries was registered using the mean PI of the two uterine arteries. In case of notch, "Notch-Index" was defined as (C-D)/C with D = post-systolic nadir and C = following zenith of the waveform. Outcome variables were placental abruption, pre-eclampsia, intrauterine growth retardation, intrauterine/neonatal death and preterm delivery before 32 completed gestational weeks. To discriminate normal and pathological waveform, incidence of adverse pregnancy outcome was related to four different definitions of pathological waveform. To describe the severity of impairment of perfusion, the frequency of adverse pregnancy outcome was related to different classes of impedance. RESULTS: To find a simple discrimination between normal and pathological uterine perfusion, best diagnostic performance was reached by a definition using a combination of high impedance and notch (no notch and mean PI > P'95 or unilateral notch and mean PI > P'90 or bilateral notch and mean PI > P'50). The prevalence of notch in nulliparae (8.5%) was higher than in parae (4.7%) and decreased with increasing gestational age (20 weeks: 8.6%-23 weeks: 5.4%). We found a clear relation between elevation of impedance, depth of notch and frequency of adverse pregnancy outcome with a frequency of complications varying from 3.2% (mean PI < or = 0.8, mean NI = 0.1) to 38.4% (mean PI > 2.0, mean NI > 0.1). CONCLUSION: Doppler sonography of the uterine arteries at 20-23 weeks has the capacity to predict at least a part of severe forms of adverse pregnancy outcome and to assess the probability of complications by quantification of the impairment of the uterine blood flow.

Abruptio Placentae↗
PubMed2005

The effect of femoral notching during total knee arthroplasty on the prevalence of postoperative femoral fractures and on clinical outcome.

BACKGROUND: The treatment of a supracondylar femoral fracture following total knee arthroplasty is complicated by the presence of the prosthetic components. Anterior femoral notching during arthroplasty has been implicated as a contributing risk factor for femoral fracture. We retrospectively reviewed the effect of anterior femoral notching on the subsequent occurrence of a periprosthetic supracondylar fracture of the distal aspect of the femur and the outcomes of primary total knee arthroplasty in such patients. METHODS: The prevalence and depth of femoral notching were determined on a review of the lateral radiographs by observers blinded to the clinical results of 1089 consecutive total knee replacements performed in 1997 and 1998. Linear and logistic regression modeling was used to analyze the relationship between femoral notching and the prevalence of supracondylar femoral fracture, postoperative range of motion, the Knee Society score, and the Knee Society functional and pain scores. RESULTS: Femoral notching was performed in 325 (29.8%) of the 1089 knees in our series. During an average follow-up period of 5.1 years, only two supracondylar femoral fractures occurred, both in femora treated without notching. Femoral notching was not associated with an increased rate of fracture (p = 1.000) or with significant differences in the measures of outcome (range of motion [p = 0.117], knee score [p = 0.967], functional score [p = 0.861], need for a lateral release [p = 0.234], or postoperative pain [p = 0.948]). CONCLUSIONS: This study demonstrated no difference in knees managed with or without notching of the anterior distal aspect of the femur with respect to the occurrence of a supracondylar fracture, range of motion, Knee Society score, Knee Society function, or pain.

Adult↗
PubMed2001

Comparison of the radius of curvature of the ulnar trochlear notch of Rottweilers and Greyhounds.

OBJECTIVE: To compare radius of curvature along the ulnar trochlear notch of Rottweilers and Greyhounds to determine whether morphologic differences exist that may contribute to the cause and pathogenesis of fragmented coronoid process in Rottweilers. SAMPLE POPULATION: Paired elbow joints from 13 Rottweilers and 14 Greyhounds. PROCEDURE: Elbow joints were radiographically scored on the basis of severity of osteoarthritic lesions. The articular contour of each ulnar trochlear notch was digitized. The radius of curvature at defined points along the ulnar trochlear notch was compared between breeds. RESULTS: Radius of curvature of the ulnar trochlear notch was not a constant function of arc length in either breed but had a consistent characteristic appearance in both breeds. Radius of curvature was greatest at each end of the ulnar trochlear notch and had 2 peaks in the midportion of the notch in both breeds. These peaks occurred farther distally in the notch and were larger in Rottweiler ulnae than Greyhound ulnae. A significant difference in mean radius of curvature was detected between breeds at these peaks. Greyhounds had significantly greater mean radius of curvature at the end of the medial coronoid process, compared with Rottweilers. CONCLUSIONS AND CLINICAL RELEVANCE: Radius of curvature of the ulnar trochlear notch is a complex function of arc length in Rottweilers and Greyhounds. The waveform has a consistent characteristic appearance in both breeds. Although significant differences were identified between breeds, associations between these differences and cause or pathogenesis of fragmented coronoid process in Rottweilers were not apparent.

Animals↗
PubMedDate not supplied

Analyses of notches in audioscan and DPOAEs in subjects with normal hearing.

In this study, the parameters of notches in the Audioscan have been compared with the distortion product otoacoustic emission (DPOAE) findings in 100 subjects with normal hearing, including 55 normal controls and 45 patients with King Kopetzky syndrome. Of those, 35 subjects had Audioscan notches (11 controls and 24 patients), 96 per cent (53 out of 55 notches) of which were associated with notches in DPOAEs. Analyses showed that the notch centre frequencies obtained in the Audioscan test correlated significantly with those of the notches found on the distortion product audiogram (DP-gram). In addition, the width of notches of the two procedures was also significantly correlated. It is likely, therefore, that such notches on Audioscan and DPOAE testing reflect localized areas of impaired cochlear function.

Adolescent↗
PubMed2005

Impairment of thymocyte development by dominant-negative Kuzbanian (ADAM-10) is rescued by the Notch ligand, delta-1.

Although Notch plays a crucial role in T cell development, regulation of Notch signaling in the thymus is not well understood. Kuzbanian, an ADAM protease, has been implicated in the cleavage of both Notch receptors and the Notch ligand, Delta. In this study we show that the expression of a dominant-negative form of Kuzbanian (dnKuz) leads to reduced TCRbeta expression in double-negative thymocytes and to a partial block between the double-negative to double-positive stages of development. These defects were rescued by overexpression of Delta-1 on thymocytes. Mixed chimeras showed a cell-autonomous block by dnKuz, but non-cell-autonomous rescue by Delta-1. This suggests that dnKuz impairs Notch signaling in receiving cells, and increasing Delta-1 on sending cells overcomes this defect. Interestingly, the expression of an activated form of Notch-1 rescued some, but not all, the defects in dnKuz Tg mice. Our data suggest that multiple Notch-dependent steps in early thymocyte development require Kuzbanian, but differ in the involvement of other Notch signaling components.

ADAM Proteins↗