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PubMed2000

Abnormal lateral notch in knees with anterior cruciate ligament injury.

We reviewed plain radiograms of anterior cruciate ligament injuries to determine the frequency of an abnormal lateral notch found in the lateral femoral condyle, and we investigated a possible mechanism for its occurrence by determining the relationship with associated injuries. We analyzed data for 216 patients who underwent ACL reconstruction between 1993 and 1996, whose radiographic images of the contralateral knee were available. The numbers of male and female patients were 122 and 94, respectively, and their ages ranged from 14 to 47 years (average, 25 years). The abnormal notch visualized by lateral radiograph was found in 66 of 216 knees (30. 6%) and was classified into three types. The type of abnormal notch seen most frequently (73%) was located at the same site as the notch on the contralateral side, but appeared deeper than normal. Knees with abnormal notches showed lateral meniscal injuries more frequently than those without such notches (P<0.005). The abnormal notch was assumed to have formed at the time of injuries, after impingement of the lateral femoral condyle on the lateral tibial condyle. Cartilage damage at the abnormal notch should be carefully observed in the future.

Adolescent↗
PubMed1992

Expression analysis of a Notch homologue in the mouse embryo.

The Drosophila Notch gene has been shown to be involved in the determination of fate in a number of different cell types. Similarly, Notch homologues in Caenorhabditis elegans are involved in cell decision-making steps. It is of interest to determine if a mammalian Notch homologue plays a role in cell fate determination. We have isolated cDNA from a mouse Notch gene using low-stringency hybridization with probes derived from the Xenopus Notch gene. Sequence analysis reveals that this gene possesses EGF repeats, Notch/lin-12 repeats, and CDC-10/SWI-6 repeats, characteristic of other Notch homologues. Northern analysis revealed that the transcript size was roughly 10 kb as has been found for the other Notch genes. We have studied the expression pattern of the gene by both conventional and whole mount in situ hybridization. Expression patterns were consistent with mouse Notch having a determinative role in the formation of mesoderm, somites, and the nervous system.

Amino Acid Sequence↗
PubMed1982

Auditory brain stem potentials evoked by clicks in notch-filtered masking noise.

Auditory brain stem evoked potentials (ABEPs) were recorded in response to wide-band clicks in notch-filtered masking noise. Notches (1/2 octave wide, 96 dB/octave slopes) were centered on the audiometric frequencies. Without the notches, masking noise intensity was adjusted to obliterate ABEPs. Intensity series, with both clicks and masking noise attenuated by the same 10 dB steps, were obtained for clicks masked by notched noise, in addition to unmasked clicks. Absolute latencies and interpeak latency differences of ABEPs to clicks in notched noise did not change with notch frequency. Absolute latencies were longer for ABEPs to clicks with notched noise than to unmasked clicks. For all stimuli, latencies were prolonged when stimulus intensity decreased. The findings suggest that ABEPs to clicks in notched noise are initiated by low threshold cochlear activation which may account for the independence of component latency from 'travelling wave' propagation time. These potentials may be representative of only one subset of the constituents of ABEPs to wide-bank unmasked clicks. The clinical application of these potentials must await elucidation of their relevance to the process of hearing.

Acoustic Stimulation↗
PubMed1987

The depth of the mandibular antegonial notch as an indicator of mandibular growth potential.

The craniofacial characteristics and growth potential of 25 orthodontically treated patients with deep mandibular antegonial notch were compared with a similar group of 25 shallow notch subjects by the use of longitudinal lateral cephalometric radiographs. Deep notch cases had more retrusive mandibles with a shorter corpus, smaller ramus height, and a greater gonial angle than did shallow notch cases. The lower facial height in the subjects with a deep mandibular notch was found to be longer, and both the mandibular plane angle and facial axis were more vertically directed. During the average 4-year period examined, the deep notch sample experienced less mandibular growth as evidenced by a smaller increase in total mandibular length, corpus length, and less displacement of the chin in a horizontal direction than did the shallow notch sample. The results of this study suggest that the clinical presence of a deep mandibular antegonial notch is indicative of a diminished mandibular growth potential and a vertically directed mandibular growth pattern.

Adolescent↗
PubMed1994

Modulation of wingless signaling by Notch in Drosophila.

Extensive genetic and molecular analyses indicate that Notch acts as a transmembrane receptor in an evolutionarily conserved cell interaction mechanism that appears to control a common step in the progression of an uncommitted cell towards the differentiated state. In Drosophila, Notch mutations were shown to affect the development of a broad spectrum of tissues, including the wing. We found that mutations in the segment polarity gene wingless are capable of acting as dominant enhancers of notchoid, a recessive Notch allele affecting the wing. The Wingless protein is homologous to the mammalian proto-oncoprotein Wnt-1 and is thought to act as the signal in a cell interaction mechanism that specifies differentiation of the embryonic epidermis as well as imaginal structures such as the wing. Although some components of the Wingless signal transduction pathway have been identified, the receptor for Wingless remains elusive. This genetic link between the Wingless and Notch pathways has been further examined by determining the relative expression patterns and subcellular localization of Notch and Wingless in mutant and wild-type backgrounds. We find that Notch is necessary for the implementation of the Wingless signal in specifying normal wing development. We discuss the possibility that Notch is directly involved in the reception of Wingless in the light of current models for the developmental action of Notch.

Animals↗
PubMed2004

Expression of Notch signalling markers in bone marrow cells that differentiate into a liver cell lineage in a rat transplant model.

Notch signalling pathway plays an important role in cell differentiation. To investigate the implications of Notch signalling in the differentiation of rat bone marrow (BM) cells into a liver cell lineage, we used cultured BM cells to examine the mRNA expression of Musashi-1, which positively regulates Notch signalling, and made a transplant model to examine the protein expression of Notch signalling markers. For the in vivo experiment, BM cells were collected from transgenic rats expressing green fluorescence protein (GFP) and transplanted into the spleens of recipient rats, in which liver damage had been induced with carbon tetrachloride. The expression of Notch receptor 1 (Notch-1), Jagged-1 and Musashi-1, in the transplanted GFP-positive BM cells was investigated by immunohistochemistry. The expression of the liver-specific proteins, alpha-fetoprotein and cytokeratin19 was also investigated. Musashi-1 mRNA became detectable in the BM cells on culture day 7 in vitro. After transplantation, GFP-positive BM cells were observed in the portal areas of the recipient's livers. Notch-1, Jagged-1, Musashi-1, alpha-fetoprotein and cytokeratin19 were all expressed in the transplanted BM cells. These results suggest that the Notch signalling pathway plays a role in the differentiation of BM cells into a liver cell lineage.

Journal Article↗
PubMed2006

T4b oral cavity cancer below the mandibular notch is resectable with a favorable outcome.

According to the AJCC 2002 staging system, squamous cell carcinoma of the oral cavity (OSCC) with T4b is unresectable. Herein, we report on our surgical outcome for T4b OSCC. All patients were enrolled before 2002. From January 1996 to December 2000, 45 consecutive untreated T4b OSCC patients were included. According to the trans-axial plane of the mandibular notch on CT/MRI, seven were supra-notch T4b and 38 were infra-notch T4b tumors. Significantly higher 5-year loco-regional control and survivals were observed in patients with infra-notch T4b than with supra-notch T4b. In the infra-notch group, pN0-1 patients had a significantly higher 5-year loco-regional control and survivals than pN2 patients. Nerve invasion was the sole significant adverse factor for loco-regional control and survivals in the infra-notch T4b group with pN0-1. Our retrospective study demonstrated that OSCC patients of infra-notch T4b with pN0-1 and no nerve invasion might have a favorable surgical outcome.

Carcinoma, Squamous Cell↗
PubMed1999

Severe uterine diastolic notch as a prognostic factor in preeclamptic women.

OBJECTIVE: To investigate the usefulness of grade II uterine diastolic notch to predict maternal or perinatal outcome during conservative management of preeclampsia. STUDY DESIGN: We reviewed medical charts of 35 pregnant women admitted for hypertension and > or =1+ urine dipstick protein determination and who had a uterine Doppler examination at admission. Grade I notch was defined as a 'nadir' in early diastole higher than half of peak diastolic notch velocity. Grade II diastolic notch was defined as a 'nadir' in early diastole lower than half of peak diastolic notch velocity. RESULTS: Thirty-one preeclamptic women were admitted at 30.1+/-3 weeks. Of them, 23 had a grade I notch (group I) and eight a grade II notch (group II). Rates of abruptio placenta, eclampsia, thrombocytopenia, stillbirth, birth weight < or = 3rd centile, fetal distress before delivery and neonatal death were similar in the two groups. Rates of delivery before 32 weeks and newborn spending more than 48 h in neonatal intensive care unit were significantly higher in group II. Admission-to-delivery interval was significantly lower in group II (2.6+/-1.5 vs. 9.4+/-8.7 days, P<0.05). CONCLUSION: Grade II notch seems to identify in preeclamptic women those with a higher risk of early pregnancy termination.

Abruptio Placentae↗
PubMed2002

Differences in three intercondylar notch geometry indices between males and females: a cadaver study.

The primary purpose of this unique evaluation of cadaveric skeletal geometry was to compare intercondylar notch geometry between males and females. One hundred male skeletons and 100 female skeletons were evaluated. Three indices of notch geometry were calculated from digital photographs of the distal femur: notch width index, notch area index, and notch shape index. Notch shape index for males exceeded that for females (P<0.004). The intercondylar notch appears less round in females and may play a role in causing ACL injuries. Future studies are required to confirm any link between notch geometry and ACL injury.

Adolescent↗
PubMed2006

Predictive role of Carhart's notch in pre-operative assessment for middle-ear surgery.

OBJECTIVES: To evaluate the predictive role of the audiometric Carhart's notch for the assessment of middle-ear pathology prior to surgical intervention. METHOD: In this retrospective analysis, a total of 315 operated ears of 305 patients were evaluated regarding their pre-operative pure tone audiograms and peri-operative findings. The probable relationship between the middle-ear pathologies found and the Carhart's notch found on pre-operative pure tone audiometry was investigated. Patients with conductive hearing loss who obtained at least a 10 dB improvement (at 1 and 2 kHz frequencies) in their bone conduction threshold post-operatively were included in the Carhart's notch group. The pathologies underlying Carhart's notch were compared. RESULTS: Three hundred and fifteen ears of 305 consecutive patients with conductive hearing loss were operated on due to middle-ear pathology. In patients with otosclerosis and tympanosclerosis, a Carhart's notch was seen at 2 kHz in 28 (93 per cent) patients but at 1 kHz in only two (7 per cent). However, in patients with chronic otitis media, a Carhart's notch was seen at 1 kHz in 10 (55 per cent) patients and at 2 kHz in eight (45 per cent) patients. CONCLUSIONS: Otitis media with effusion, tympanosclerosis and congenital malformations should be considered in the differential diagnosis of a patient with a Carhart's notch seen on pure tone audiometry. A Carhart's notch at 2 kHz indicates stapes footplate fixation, whereas one at 1 kHz indicates a mobile stapes footplate; the footplate mobility can thus be predicted pre-operatively.

Adolescent↗
PubMed2002

Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells.

Truncated Notch receptors have transforming activity in vitro and in vivo. However, the role of wild-type Notch signaling in neoplastic transformation remains unclear. Ras signaling is deregulated in a large fraction of human malignancies and is a major target for the development of novel cancer treatments. We show that oncogenic Ras activates Notch signaling and that wild-type Notch-1 is necessary to maintain the neoplastic phenotype in Ras-transformed human cells in vitro and in vivo. Oncogenic Ras increases levels and activity of the intracellular form of wild-type Notch-1, and upregulates Notch ligand Delta-1 and also presenilin-1, a protein involved in Notch processing, through a p38-mediated pathway. These observations place Notch signaling among key downstream effectors of oncogenic Ras and suggest that it might be a novel therapeutic target.

Animals↗
PubMed2005

An essential role of Pak1 phosphorylation of SHARP in Notch signaling.

The p21-activated kinases (Paks), an evolutionarily conserved family of serine/threonine kinases, play an important role in cytoskeletal reorganization in mammalian cells. The Notch signaling pathway plays an important role in the determination of cell fate/differentiation in a number of organs. Notch signaling is a complex process, and the mechanism by which Notch regulates multiple cellular processes is intriguing. The expression of both Notch and Pak1 has been shown to be deregulated in several human cancers. Using yeast two-hybrid screening, we identified SHARP, one of the Notch signaling components, as a Pak1-interacting protein. We found that SHARP is a physiologic interacting substrate of Pak1, and that this interaction enhances SHARP-mediated repression of Notch target genes. Pak1 phosphorylation sites in SHARP were mapped to Ser3486 and Thr3568 within the SHARP repression domain. Mutation of Pak1 phosphorylation sites in SHARP, inhibition of Pak1 functions by a Pak1-autoinhibitory fragment (amino acids 83-149), or expression of Pak1-specific siRNA interfered with SHARP-mediated repression of Notch target reporter gene activation. These results demonstrate that Pak1-SHARP interaction plays an essential role in enhancing the corepressor functions of SHARP, thereby modulating Notch signaling in human cancer cells.

3T3 Cells↗
PubMed1997

A cross-sectional study of platelet volume in healthy normotensive women with bilateral uterine artery notches.

High uterine artery resistance characterized by bilateral notches seen on Doppler ultrasound in the second half of pregnancy is associated with an increased risk of adverse outcome related to pre-eclampsia and intrauterine growth retardation. We sought to establish whether there was a difference in platelet volume in healthy, normotensive women with high-resistance uterine artery Doppler findings compared to those with normal uterine artery Doppler findings. Forty-seven women were allocated prospectively into 'bilateral notch' and 'no notch' groups at color Doppler imaging of the uterine arteries carried out at a mean of 26 weeks' gestation. The difference in platelet volume between the two groups and the relationship of adverse outcome with raised platelet volume and high-resistance uterine artery Doppler findings was investigated. Twenty-three women had no evidence of uterine artery notches and 24 had bilateral uterine artery notches. Platelet volume in the women with bilateral notches was greater than in those with no notches (8.28 fl vs. 7.46 fl; p = 0.01). However, unlike high-resistance uterine artery Doppler findings, increased platelet volume was not associated with adverse outcome. Uterine artery Doppler flow abnormalities have not previously been studied in combination with hematological or biochemical markers. Our findings show, for the first time, that women with bilateral uterine artery notches have an increased platelet volume compared to those with normal uterine artery Doppler findings many weeks before clinical signs of pre-eclampsia or fetal growth retardation are evident. Women with abnormal uterine artery flow at this gestation may have other cardiovascular and hematological differences compared to those with normal flow.

Arteries↗
PubMed2001

Evaluation of the sigmoid notch with computed tomography following intra-articular distal radius fracture.

A classification system for disruption patterns of the sigmoid notch of the radius associated with distal radius fractures has not been established. Using plain x-rays and corresponding computed tomography (CT) scans we characterized and quantified the types of sigmoid notch involvement in 20 consecutive distal radius fractures with radiocarpal joint extension. Plain radiographs revealed fracture extension into the sigmoid notch in only 7 cases (35%) and the CT scans demonstrated fracture extension into the sigmoid notch in 13 cases (65%). Of the 13 fractures with sigmoid notch involvement, 9 (69%) were displaced and 4 (31%) were nondisplaced. Sigmoid notch articular step-off (n = 7) and gapping (n = 9) were detectable on the CT scans but not on the x-rays. Plain x-rays appear to underestimate sigmoid notch involvement following distal radius fractures. In addition, CT appears to be a superior diagnostic modality for quantifying sigmoid notch fracture step-off and articular gapping.

Adult↗
PubMed2003

Mechanism and incidence of notched pulmonary venous atrial reversal wave.

In certain patients, pulmonary venous flow pattern obtained by the pulsed wave Doppler during transesophageal echocardiography shows a notching on the atrial reversal (A) wave. However, the incidence or the mechanism of this notched A wave has not been described. After transthoracic echocardiographic evaluation for the chamber sizes, wall thickness, and left-ventricular function, transesophageal echocardiography was performed in 100 patients with in sinus rhythm. Discernible pulmonary venous A wave was observed in 46 patients. Among these 46 patients, notched A wave was observed in 11 (31%). In 4 patients with notched A wave, left-atrial pressure waveforms could be obtained during mitral balloon valvuloplasty. In all these patients, left-atrial pressure waveforms showed prominent c waves. In 2 patients, transesophageal echocardiography was repeated after mitral balloon valvuloplasty. Late peak of the notched A wave decreased with the decrease in the magnitude of rise in left-atrial c wave. Among the transthoracic echocardiographic parameters, patients with notching (n = 11) had significantly larger left atriums than patients without notching (n = 35)(49.3 +/- 6.2 vs 37.3 +/- 4.4 mm, P <.0001). There were no significant differences in left-ventricular dimensions, wall thickness, and ejection fraction. In conclusion, notched pulmonary venous A wave indicates the presence of left-atrial c wave; and presence of left-atrial c wave may represent decreased left-atrial compliance.

Adult↗
PubMed2005

Direct regulation of intestinal fate by Notch.

The signals that maintain the proper balance between adult intestinal cell types are poorly understood. Loss-of-function studies have implicated the Notch pathway in the regulation of intestinal fate during development. However, it is unknown whether Notch has a role in maintaining the balance of different cell types in the adult intestine and whether it acts reversibly. To determine whether Notch has a direct effect on intestinal development and adult intestinal cell turnover, we have used a gain-of-function approach to activate Notch. Ectopic Notch signaling in adult intestinal progenitor cells leads to a bias against secretory fates, whereas ectopic Notch activation in the embryonic foregut results in reversible defects in villus morphogenesis and loss of the proliferative progenitor compartment. We conclude that Notch regulates adult intestinal development by controlling the balance between secretory and absorptive cell types. In the embryo, Notch activation perturbs morphogenesis, possibly through effects on stem or progenitor cells.

Animals↗
PubMed1983

Molecular cloning of Notch, a locus affecting neurogenesis in Drosophila melanogaster.

The Notch locus is one of the best characterized loci in Drosophila melanogaster in terms of its genetic structure and developmental effects. Mutations in this locus profoundly affect the differentiation of the early embryo. Using an inversion involving the Notch locus and previously cloned sequences, we have isolated chromosomal segments from the Notch region (3C7) encompassing 80 kilobases (kb) of DNA. Based on comparison between mutant and wild-type DNA, we have positioned cloned sequences within the Notch genetic map; furthermore, we have defined a region of approximately 40 kb within which the structural lesions correlating with all Notch alleles mapped to date appear to reside. We have examined the transcriptional activity of the cloned sequences during ontogeny and find a single size class of poly(A)+ RNA, 10.5 kb long, that is homologous to sequences within this 40-kb region. We conclude that DNA sequences belonging to the Notch locus have been cloned and that the 10.5-kb poly(A)+ RNA is essential for wild-type Notch function. We discuss these structural and transcriptional data in light of the existing genetic and developmental characterization of the Notch locus.

Animals↗
PubMed2005

A prospective analysis of the role of uterine artery Doppler waveform notching in the assessment of at-risk pregnancies.

OBJECTIVE: To determine the value of second trimester uterine artery Doppler waveform notching in the prediction of adverse pregnancy outcome in a high-risk group. DESIGN: Analysis of data from a consecutively collected cohort. SETTING: St. James University Hospital, Leeds, UK. POPULATION: Three hundred thirty women known to be at risk of preeclampsia (PET) or intrauterine growth restriction (IUGR) were assessed for notching of the uterine artery Doppler waveform between 24-30 weeks of pregnancy. MAIN OUTCOME MEASURES: Preeclampsia (PET), small-for-gestational-age at birth (SGA), preterm delivery (PTD), perinatal death. RESULTS: Two hundred thirty-two women (70.3%) had a normal uterine artery Doppler waveforms, and 98 (29.7%) demonstrated either unilateral or bilateral notching. In women where notching was present, 20 (20%) developed PET compared with 8 (3.5%) in the normal group [Odds ratio (OR) 7.2, CI 3-17]; SGA birthweight was present in 24 (24.5%) of the notched group and in 21 (9%) of normal group (OR 3.3; CI 1.7-6.2); 40 (41%) of the notched group delivered preterm ( < 37 weeks) as compared with 37 (16%) of the normal group (OR 7.9; CI 4.6-13). This difference was even more marked when delivery before 32 weeks was considered, occurring in 8 (8%) of the notched group and 4 (1.7%) of the normal group (OR 11.5; CI 4.5-29.4). Of the six perinatal deaths, five (5.1%) occurred in the notched group (OR 12.4; CI 1.4-108). CONCLUSION: This study demonstrates that the addition of uterine Doppler waveform analysis to the monitoring profile of women at risk of PET, SGA, IUD and preterm delivery can further define those in a higher risk group and the majority that have a risk no higher than the background.

Adult↗