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PubMed1996

Neuropsychological findings in a patient with Kernohan's notch.

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

Journal Article↗
PubMed2007

Increased Notch 1 expression and attenuated stimulatory G protein coupling to adenylyl cyclase in osteonectin-null osteoblasts.

Osteonectin, or secreted protein acidic and rich in cysteine, is one of the most abundant noncollagen matrix components in bone. This matricellular protein regulates extracellular matrix assembly and maturation in addition to modulating cell behavior. Mice lacking osteonectin develop severe low-turnover osteopenia, and in vitro studies of osteonectin-null osteoblastic cells showed that osteonectin supports osteoblast formation, maturation, and survival. The present studies demonstrate that osteonectin-null osteoblastic cells have increased expression of Notch 1, a well-documented regulator of cell fate in multiple systems. Furthermore, osteonectin-null cells are more plastic and less committed to osteoblastic differentiation, able to pursue adipogenic differentiation given the appropriate signals. Notch 1 transcripts are down-regulated by inducers of cAMP in both wild-type and osteonectin-null osteoblasts, suggesting that the mutant osteoblasts may have a defect in generation of cAMP in response to stimuli. Indeed, many bone anabolic agents signal through increased cAMP. Wild-type and osteonectin-null osteoblasts generated comparable amounts of cAMP in response to forskolin, a direct stimulator of adenylyl cyclase. However, the ability of osteonectin-null osteoblasts to generate cAMP in response to cholera toxin, a direct stimulator of Gs, was attenuated. These data imply that osteonectin-null osteoblasts have decreased coupling of Gs to adenylyl cyclase. Because osteonectin promotes G protein coupling to an effector, our studies support the concept that low-turnover osteopenia can result from reducing G protein coupled receptor activity.

Adenylyl Cyclases↗
PubMed2004

Transcranial motor evoked potential recording in a case of Kernohan's notch syndrome: case report.

OBJECTIVE AND IMPORTANCE: Compression of the cerebral peduncle against the tentorial incisura contralateral to a supratentorial mass lesion, the so-called Kernohan-Woltman notch phenomenon, can be an important cause of false localizing motor signs. Here, we demonstrate a case in which clinical, radiological, and electrophysiological findings were used together to define this syndrome. CLINICAL PRESENTATION: A 21-year-old man sustained a left temporal depressed cranial fracture from a motor vehicle accident. Serial computed tomographic examinations demonstrated no evolution of hematomas or contusions, and he was managed nonsurgically with ventriculostomy for intracranial pressure control. Throughout his course in the neurosurgical intensive care unit, he displayed persistent left hemiparesis. INTERVENTION: Further radiological and electrophysiological studies were undertaken in an attempt to explain his left hemiparesis. Brain magnetic resonance imaging demonstrated T2 prolongation in the central portion of the right cerebral peduncle extending to the right internal capsule. Electrophysiological studies using transcranial electrical motor evoked potentials revealed both a marked increase in voltage threshold, as well as a reduction in the complexity of the motor evoked potential waveform on the hemiparetic left side. This contrasted to significantly lower voltage threshold as well as a highly complex motor evoked potential waveform recorded on the relatively intact contralateral side. CONCLUSION: This is the first time that clinical, radiological, and electrophysiological findings have been correlated in a case of Kernohan's notch syndrome. Compression of the contralateral cerebral peduncle against the tentorial incisura can lead to damage and ipsilateral hemiparesis. The anatomic extent of the lesion can be defined by magnetic resonance imaging and the physiological extent by electrophysiological techniques.

Adult↗
PubMed1994

An activated Notch suppresses neurogenesis and myogenesis but not gliogenesis in mammalian cells.

P19 cells, a mouse embryonal carcinoma line, can be induced to differentiate into neurons. After induction, however, only a small subpopulation of cells develop as neurons, suggesting that equipotent cells adopt different cell fates. In invertebrate systems, the lin-12-Notch family of genes is thought to control the choice of cell fate. We have therefore asked whether activation of murine Notch (mNotch) regulates neuronal differentiation in P19 cells. We demonstrate that a dominant gain-of-function mutant of mNotch suppresses neurogenesis, as well as myogenesis in P19 cells. Overexpression of the full-length mNotch protein also suppresses neurogenesis. In contrast, the differentiation of glia is not affected by an activated mNotch homologue. These data indicate that mNotch may play a central role in the choice of cell fate in differentiating cells in culture and suggests that mNotch may play a similar role in the choice of fate in the developing mammalian embryo.

Animals↗
PubMed1997

The Notch ligand, X-Delta-2, mediates segmentation of the paraxial mesoderm in Xenopus embryos.

Segmentation of the vertebrate embryo begins when the paraxial mesoderm is subdivided into somites, through a process that remains poorly understood. To study this process, we have characterized X-Delta-2, which encodes the second Xenopus homolog of Drosophila Delta. Strikingly, X-Delta-2 is expressed within the presomitic mesoderm in a set of stripes that corresponds to prospective somitic boundaries, suggesting that Notch signaling within this region establishes a segmental prepattern prior to somitogenesis. To test this idea, we introduced antimorphic forms of X-Delta-2 and Xenopus Suppressor of Hairless (X-Su(H)) into embryos, and assayed the effects of these antimorphs on somite formation. In embryos expressing these antimorphs, the paraxial mesoderm differentiated normally into somitic tissue, but failed to segment properly. Both antimorphs also disrupted the segmental expression of X-Delta-2 and Hairy2A, a basic helix-loop-helix (bHLH) gene, within the presomitic mesoderm. These observations suggest that X-Delta-2, via X-Notch-1, plays a role in segmentation, by mediating cell-cell interactions that underlie the formation of a segmental prepattern prior to somitogenesis.

Animals↗
PubMed2000

Notch signaling regulates the pattern of auditory hair cell differentiation in mammals.

The development of the mammalian cochlea is an example of patterning in the peripheral nervous system. Sensory hair cells and supporting cells in the cochlea differentiate via regional and cell fate specification. The Notch signaling components shows both distinct and overlapping expression patterns of Notch1 receptor and its ligands Jagged1 (Jag1) and Jagged2 (Jag2) in the developing auditory epithelium of the rat. On embryonic day 16 (E16), many precursor cells within the Kölliker's organ immunostained for the presence of both Notch1 and Jag1, while the area of hair cell precursors did not express either Notch1 and Jag1. During initial events of hair cell differentiation between E18 and birth, Notch1 and Jag1 expression predominated in supporting cells and Jag2 in nascent hair cells. Early after birth, Jag2 expression decreased in hair cells while the pattern of Notch1 expression now included both supporting cells and hair cells. We show that the normal pattern of hair cell differentiation is disrupted by alteration of Notch signaling. A decrease of either Notch1 or Jag1 expression by antisense oligonucleotides in cultures of the developing sensory epithelium resulted in an increase in the number of hair cells. Our data suggest that the Notch1 signaling pathway is involved in a complex interplay between the consequences of different ligand-Notch1 combinations during cochlear morphogenesis and the phases of hair cell differentiation.

Animals↗
PubMed2002

Bimodal functions of Notch-mediated signaling are involved in neural crest formation during avian ectoderm development.

Neural crest is induced at the junction of epidermal ectoderm and neural plate by the mutual interaction of these tissues. In previous studies, BMP4 has been shown to pattern the ectodermal tissues, and BMP4 can induce neural crest cells from the neural plate. In this study, we show that epidermally expressed Delta1, which encodes a Notch ligand, is required for the activation and/or maintenance of Bmp4 expression in this tissue, and is thus indirectly required for neural crest induction by BMP4 at the epidermis-neural plate boundary. Notch activation in the epidermis additionally inhibits neural crest formation in this tissue, so that neural crest generation by BMP4 is restricted to the junction.

Animals↗
PubMed2005

Regulation of acquired immune system by notch signaling.

T- and B-cells are generated from hematopoietic stem cells through lymphoid intermediates. The interplay of intrinsic and extrinsic signals determines cell fate at the branch point for T- and B-cell lineages and at the post-commitment stage of lymphogenesis. The mature lymphocytes differentiate into effector/memory cells by antigen recognition, and those differentiation steps are also governed by a series of cell fate choices and survival signals, which allows cells to acquire distinct effector functions. The identification of the molecular details that dictate lymphocyte development and differentiation will improve understanding of acquired immune responses. Recent studies have revealed that Notch molecules, evolutionarily conserved transmembrane receptors, play key roles in lymphocyte development and differentiation. In this article, we review recent knowledge regarding the roles of Notch signaling in controlling both lymphocyte development and acquisition of effector functions.

Animals↗
PubMed1995

CT percutaneous biopsy guns: comparison of end-cut and side-notch devices in cadaveric specimens.

OBJECTIVE: The purpose of this study was to compare the efficacies of four different types of end-cut biopsy guns with the side-notch Tru-cut biopsy gun. MATERIALS AND METHODS: A total of 25 liver, 15 kidney, 10 pancreas, and 15 breast biopsies were performed in the tissue from five autopsies with each of 12 different biopsy devices/biopsy depths. The tissue obtained was evaluated by an experienced cytopathologist who, not knowing which gun was used to obtain each specimen, used a predetermined grading scheme. RESULTS: When tissue was obtained, the end-cut biopsy guns performed equivalently to the side-notch biopsy gun in all four tissues. However, the end-cut guns had a significant number of "zero" biopsies (biopsy attempts during which no tissue was obtained). The proportion of zero biopsies with the end-cut guns ranged from up to 28% in the liver to 60% and 73% in the breast and kidney, respectively. CONCLUSION: The end-cut biopsy guns are easy to use and potentially can obtain high-quality specimens. However, the rate of zero biopsies during which no tissue is obtained is a serious deficiency. As a result, the use of the end-cut biopsy gun should be encouraged only for use with an introducer, with which multiple biopsy specimens can easily be obtained without additional needle punctures.

Biopsy, Needle↗
PubMed1983

High-pass and notch noise masking in suprathreshold brainstem response audiometry.

The combination of suprathreshold tone-bursts with frequency of 0.5, 1 or 2 kHz and ipsilateral high-pass (HP) or notch noise masking has been studied in 52 adults referred for otoneurological examination on account of unilateral or asymmetric high-frequency hearing loss. Wave V latency changes are similar for both HP and notch noise masking and, in accordance with cochlear tonotopicity, are greater for the lower stimulus frequencies. Results are, however, not always conclusive with either technique, and response identification is problematical at 0.5 kHz. The less demanding HP masking technique is considered the method of choice since possible influence from the stapedius reflex is minimal and a better signal-noise ratio obtained.

Acoustic Stimulation↗
PubMed1994

Carhart notch and electric bone-conduction audiometry.

The Carhart notch is a depression in the bone-conduction audiogram of patients with clinical otosclerosis. The middle frequencies from 0.5 to 2 kHz, which correspond to the resonance frequency of the middle ear, can be substantially improved following successful stapes surgery. Twenty-nine consecutive patients with clinical otosclerosis were tested 2 weeks before and 7 months after stapes surgery with conventional air-conduction (AC) and bone-conduction (BC) audiometry and electric bone-conduction (EBC) audiometry using an Audimax 500 audiometer. The BC thresholds improved at 0.5-2.0 kHz corresponding to the Carhart notch. On average, the EBC thresholds remained more stable, showing no Carhart phenomenon, which supports the concept that EBC stimulation is not entirely equivalent to conventional BC audiometry, but has a different mode of action on the inner ear.

Adult↗
PubMed1995

Kernohan's notch in chronic subdural hematoma: findings on magnetic resonance imaging.

A 69-year-old man presented with mild left-sided hemiparesis of 2 years' duration. A computerized tomography scan revealed a left-sided chronic subdural hematoma and a midline shift to the right. Magnetic resonance (MR) imaging obtained on admission to the hospital also disclosed a deformity of the right crus cerebri. After drainage and irrigation of the hematoma through a single burr hole, the left hemiparesis improved significantly. Magnetic resonance imaging performed 9 days after the operation revealed that the size of the subdural hematoma had diminished and the deformity of the crus cerebri had improved markedly. Kernohan's notch, caused by a supratentorial mass and producing ipsilateral hemiparesis or hemiplegia, is rarely demonstrated radiographically. This may be the first reported case in which Kernohan's notch in chronic subdural hematoma has been demonstrated on MR imaging.

Aged↗
PubMed2003

Notch signaling induces multilineage myeloid differentiation and up-regulates PU.1 expression.

Hemopoietic commitment is initiated by and depends on activation of transcription factors. However, it is unclear whether activation of lineage-affiliated transcription factors is extrinsically regulated by to date unknown agents or is the result of a cell autonomous program. Here we show that signaling by the Notch1 transmembrane receptor instructively induces myeloid differentiation of multipotent hemopoietic progenitor cells and concomitantly up-regulates the expression of the transcription factor PU.1. Transient activation of Notch1 signaling is sufficient to irreversibly reduce self-renewal of multipotent progenitor cells accompanied by increased and accelerated differentiation along the granulocyte, macrophage, and dendritic cell lineages. Activated Notch1 has no direct influence on apoptosis of multipotent progenitor cells, shows a weak inhibition of proliferation, and does not substitute for survival and proliferation signals provided by cytokines. Activated Notch1 directly increases PU.1 RNA levels, leading to a high concentration of PU.1 protein, which has been shown to direct myeloid differentiation. These findings identify Notch as an extrinsic regulator of myeloid commitment, and the lineage-affiliated transcription factor PU.1 as a specific direct target gene of Notch.

Animals↗
PubMed1976

Destruction of hyaline cartilage in the sigmoid notch of the human ulna.

In an ulna from an adolescent a fossa nudata divided the articular surface of the sigmoid notch into olecranon and coronoid areas. In the floor of the fossa a layer of loose avascular pannus covered a thin layer of articular cartilage. The pannus appeared to have been formed by removal of chondroitin from the cartilage, freeing the cells and unmasking the fibres. Probably the change followed loss of contact between the articular cartilages of the sigmoid notch and trochlea during postnatal growth.

Adolescent↗
PubMed2001

Expression patterns of Notch1, Notch2, and Notch3 suggest multiple functional roles for the Notch-DSL signaling system during brain development.

The Notch-DSL signaling system consists of multiple receptors and ligands, and plays many roles in development. The function of Notch receptors and ligands in mammalian brain, however, is poorly understood. In the current study, we examined the expression patterns for three receptors of this system, Notch1, 2, and 3, in late embryonic and postnatal rat brain by in situ hybridization. The three receptors have overlapping but different patterns of expression. Messenger RNA for all three proteins is found in postnatal central nervous system (CNS) germinal zones and, in early postnatal life, within numerous cells throughout the CNS. Within zones of cellular proliferation of the postnatal brain, Notch1 mRNA is found in both the subventricular and the ventricular germinal zones, whereas Notch2 and Notch3 mRNAs are more highly localized to the ventricular zones. Both Notch1 and Notch3 mRNAs are expressed along the inner aspect of the dentate gyrus, a site of adult neurogenesis. Notch2 mRNA is expressed in the external granule cell layer of the developing cerebellum. In several brain areas, Notch1 and Notch2 mRNAs are relatively concentrated in white matter, whereas Notch3 mRNA is not. Neurosphere cultures (which contain CNS stem cells), purified astrocyte cultures, and striatal neuron-enriched cultures express Notch1 mRNA. However, in these latter cultures, Notch1 mRNA is produced by nestin-containing cells, rather than by postmitotic neurons. Taken together, these results support multiple roles for Notch1, 2, and 3 receptor activation during CNS development, particularly during gliogenesis.

Animals↗
PubMed2003

Anomalous traversement of the suprascapular artery through the suprascapular notch: a possible mechanism for undiagnosed shoulder pain?

BACKGROUND: The literature is deficient in studies aimed at quantifying the occurrence of a suprascapular artery traversing the suprascapular notch with the suprascapular nerve. MATERIAL/METHODS: We have performed a cadaveric study using 60 adult specimens (120 sides). Thirty-eight specimens were male and twenty-two were female. RESULTS: Our findings conclude that in this group, the suprascapular artery travels with the suprascapular nerve through the suprascapular notch in 2.5% of specimen sides. Both specimens in whom this occurred were male. CONCLUSIONS: We hypothesize that this anatomic anomaly may also constitute a possible unrecognized mechanism in which shoulder pain is generated. Further studies focused at various races and the presence of this peculiarity are now needed to confirm our findings. In addition, unexplained chronic shoulder pain may be explored with vascular studies aimed at identifying the course of the suprascapular artery.

Adult↗
PubMed1992

[Suprascapular nerve entrapment at the spinoglenoid notch].

The suprascapular nerve passes through the spinoglenoid notch with a risk of entrapment. This results in distal nerve lesion characterized by isolated paralysis of the infraspinatus muscle and, most often, by shoulder pain. We report 7 clinical and electromyographical cases of pure infraspinatus muscle paralysis. The value of the electrodiagnosis, which demonstrated prolonged suprascapular distal nerve latencies (over 5 milliseconds) in the infraspinatus muscle affected while latencies were normal in the supraspinatus muscle, is emphasized. Mechanical factors were associated with paralysis in 5 cases. Compressive synovial cysts were found in 2 patients operated upon. Surgical enlargement of the spinoglenoid notch regularly and rapidly relieves pain and sometimes helps in recovery of the infraspinatus muscle.

Adolescent↗