Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “NUMB”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources
PubMed1994

The Numbing Scale: psychometric properties, a preliminary report.

This study explored the psychometric properties of a new self-report instrument, The Glover Numbing Scale. The scale measures a variety of behaviors reported by individuals experiencing an inability to access feelings other than hostility and rage. The scale was administered to inpatient Vietnam combat veterans with post-traumatic stress disorder (PTSD, n = 323), PTSD diagnosed Veterans Affairs (VA) outpatient and veterans' outreach center veterans (n = 208), two Vietnam veteran noncombat groups (n = 45), two psychiatric noncombat controls (anxiety disorder, n = 40; major depressive disorder, n = 31), and a nonpsychiatric never-in-Vietnam veteran control group (n = 48). Reliability information suggested that the scale was internally consistent with good test-retest correlations. Convergent and discriminant validations were assessed based on the pattern of the scale's correlations with relevant Minnesota Multiphasic Personality Inventory (MMPI) scales. The contrasting pattern of correlations provided by a subgroup of veterans who reported always feeling dead or shut down was highlighted. Principal component analysis resulted in a five factor solution that provided evidence for the scale's factorial validity. Numbing Scale scores discriminated levels of psychopathology within the veteran population. PTSD outreach center veterans' sum scores and item scores on the Numbing Scale were more similar to responses of anxiety disorder patients than to major depressive disorder patients. Overall, the findings strongly support the clinical application of the Numbing Scale.

Adult↗
PubMed2005

Notch 1 interacts with the amyloid precursor protein in a Numb-independent manner.

We hypothesized that the physical interaction between the amyloid precursor protein (APP) and Notch 1 (N1) may be mediating the reported cross-talk between the respective signaling pathways. Immunoprecipitation of mouse N1 (mN1) or extracellular domain truncated mN1 (mN1-TM, mimics TACE-produced membrane-bound C-terminal fragment) specifically coprecipitated APP(751). Conversely, immunoprecipitation of APP(751) specifically coprecipitated mN1, furin-generated membrane-bound mN1 C-terminal fragment (f.mN1-TM), or mN1-TM. The London mutation of APP did not affect the APP(751)/mN1 interaction. Coexpression of APP(751) and mN1 did not affect APP processing or production of mN1 intracellular domain (mNICD). The APP(751)/mN1 interaction was Numb-independent, insofar as it was observed in HEK293 cells that lack detectable levels of Numb and was unaffected by the expression of exogenous Numb or deletion of the APP cytoplasmic domain, including the Numb-binding YENPTY sequence. This interaction was unaffected even when the N-terminal 647 amino acids of APP were replaced by a sequence of secreted alkaline phosphatase. These data combined with data showing interaction between mN1-TM and APP(751) suggest that their transmebrane domains and short sequences around them are sufficient for the interaction and that APP(751) and mN1 interact in cis. Our results imply novel functions of APP and/or N1 that derive from their interaction.

Alzheimer Disease↗
PubMed1989

numb, a gene required in determination of cell fate during sensory organ formation in Drosophila embryos.

Neurons and support cells of each sensory organ in Drosophila embryos are most likely derived from a single precursor cell. This cell lineage is affected in numb mutants. Morphological alterations of sensory structures, as well as changes in the number of cells expressing cell type-specific markers, indicate that sensory neurons in numb mutant embryos are transformed into lineage-related nonneuronal support cells. Thus the numb gene controls the fate of progeny derived from sensory organ precursors. The numb gene has been isolated by the plasmid rescue method. The structure of its predicted product is discussed.

Amino Acid Sequence↗
PubMed1995

tramtrack acts downstream of numb to specify distinct daughter cell fates during asymmetric cell divisions in the Drosophila PNS.

Asymmetric cell divisions allow a sensory organ precursor (SOP) cell to generate a neuron and its support cells in the Drosophila PNS. We demonstrate a role of tramtrack (ttk), previously identified as a zinc finger-containing putative transcription factor, in the determination of different daughter cell fates. Both loss of function and overexpression of ttk affect the fates of the SOP progeny. Whereas loss of ttk function transforms support cells to neurons, ttk overexpression results in the reverse transformation. ttk is expressed in support cells but not in neurons. It has been shown that numb, a membrane-associated protein asymmetrically distributed during the SOP division, confers different daughter cell fates. Loss of ttk or numb function results in reciprocal cell fate transformation. Epistatic studies suggest that ttk acts downstream of numb. We propose that ttk executes the command dictated by asymmetrically localized numb to specify distinct daughter cell fates during multiple asymmetric divisions.

Animals↗
PubMed2006

Notch and Numb are required for normal migration of peripheral glia in Drosophila.

A prominent feature of glial cells is their ability to migrate along axons to finally wrap and insulate them. In the embryonic Drosophila PNS, most glial cells are born in the CNS and have to migrate to reach their final destinations. To understand how migration of the peripheral glia is regulated, we have conducted a genetic screen looking for mutants that disrupt the normal glial pattern. Here we present an analysis of two of these mutants: Notch and numb. Complete loss of Notch function leads to an increase in the number of glial cells. Embryos hemizygous for the weak Notch(B-8X) allele display an irregular migration phenotype and mutant glial cells show an increased formation of filopodia-like structures. A similar phenotype occurs in embryos carrying the Notch(ts1) allele when shifted to the restrictive temperature during the glial cell migration phase, suggesting that Notch must be activated during glial migration. This is corroborated by the fact that cell-specific reduction of Notch activity in glial cells by directed numb expression also results in similar migration phenotypes. Since the glial migration phenotypes of Notch and numb mutants resemble each other, our data support a model where the precise temporal and quantitative regulation of Numb and Notch activity is not only required during fate decisions but also later during glial differentiation and migration.

Animals↗
PubMed2000

Numb chin syndrome as the presenting symptom of metastatic prostate carcinoma.

We report a case of the numb chin syndrome as the presenting symptom in a patient with metastatic prostate carcinoma. The numb chin syndrome is characterized by facial numbness along the distribution of the mental branch of the trigeminal nerve. Most cases of this syndrome that are not dental in origin have been associated with diffuse metastatic disease, particularly with underlying lymphoproliferative and breast cancer. Although axial and vertebral bone metastases are common in patients with carcinoma of the prostate, mental nerve involvement is rare. We present a case of the numb chin syndrome as the initial clinical manifestation in a patient with metastatic prostate adenocarcinoma.

Aged↗
PubMed1991

The numb chin.

An apparently innocuous complaint such as a numb chin may be associated with malignant disease, either as heralding symptom or as a manifestation of metastasis. A series of 15 patients with numbness of the chin is presented in which a malignancy was diagnosed prior to the numbness. The numbness diminished or disappeared in 66% of the patients following either systemic chemotherapy or radiotherapy.

Adolescent↗
PubMed2003

Numb inhibits membrane localization of Sanpodo, a four-pass transmembrane protein, to promote asymmetric divisions in Drosophila.

Cellular diversity is a fundamental characteristic of complex organisms, and the Drosophila CNS has proved an informative paradigm for understanding the mechanisms that create cellular diversity. One such mechanism is the asymmetric localization of Numb to ensure that sibling cells respond differently to the extrinsic Notch signal and, thus, adopt distinct fates (A and B). Here we focus on the only genes known to function specifically to regulate Notch-dependent asymmetric divisions: sanpodo and numb. We demonstrate that sanpodo, which specifies the Notch-dependent fate (A), encodes a four-pass transmembrane protein that localizes to the cell membrane in the A cell and physically interacts with the Notch receptor. We also show that Numb, which inhibits Notch signaling to specify the default fate (B), physically associates with Sanpodo and inhibits Sanpodo membrane localization in the B cell. Our findings suggest a model in which Numb inhibits Notch signaling through the regulation of Sanpodo membrane localization.

Amino Acid Sequence↗
PubMed2002

Progenitor cell maintenance requires numb and numblike during mouse neurogenesis.

Neurons in most regions of the mammalian nervous system are generated over an extended period of time during development. Maintaining sufficient numbers of progenitors over the course of neurogenesis is essential to ensure that neural cells are produced in correct numbers and diverse types. The underlying molecular mechanisms, like those governing stem-cell self-renewal in general, remain poorly understood. We report here that mouse numb and numblike (Nbl), two highly conserved homologues of Drosophila numb, play redundant but critical roles in maintaining neural progenitor cells during embryogenesis, by allowing their progenies to choose progenitor over neuronal fates. In Nbl mutant embryos also conditionally mutant for mouse numb in the nervous system, early neurons emerge in the expected spatial and temporal pattern, but at the expense of progenitor cells, leading to a nearly complete depletion of dividing cells shortly after the onset of neurogenesis. Our findings show that a shared molecular mechanism, with mouse Numb and Nbl as key components, governs the self-renewal of all neural progenitor cells, regardless of their lineage or regional identities.

Alleles↗
PubMed2006

Numb is a suppressor of Hedgehog signalling and targets Gli1 for Itch-dependent ubiquitination.

The developmental protein Numb is a major determinant of binary cell fates. It is also required for the differentiation of cerebellar granule cell progenitors (GCPs) at a stage of development responsive to the morphogenic glycoprotein Hedehog. Hedgehog signalling is crucial for the physiological maintenance and self-renewal of neural stem cells and its deregulation is responsible for their progression towards tumorigenesis. The mechanisms that inhibit this pathway during the differentiation stage are poorly understood. Here, we identify Numb as a Hedgehog-pathway inhibitor that is downregulated in early GCPs and GCP-derived cancer cells. We demonstrate that the Hedgehog transcription factor Gli1 is targeted by Numb for Itch-dependent ubiquitination, which suppresses Hedgehog signals, thus arresting growth and promoting cell differentiation. This novel Numb-dependent regulatory loop may limit the extent and duration of Hedgehog signalling during neural-progenitor differentiation, and its subversion may be a relevant event in brain tumorigenesis.

Animals↗
PubMed2002

Emotional numbing in posttraumatic stress disorder: current and future research directions.

OBJECTIVE: Despite being understudied and poorly understood relative to the chronic fear, anxiety and other aversive emotional states that occur in the immediate aftermath of trauma, emotional numbing has become a core defining feature of posttraumatic stress disorder (PTSD). METHOD: This paper seeks to briefly review the literature bearing on these seemingly disparate emotional responses to trauma as well as theoretical accounts of emotional numbing that have been proffered to date. We then offer an alternative theory of post-traumatic emotional functioning and review empirical support for this model. RESULT: The experience of trauma produces very intense emotions such as overwhelming fear, horror, and anxiety, and these reactions can linger for a lifetime. Many trauma survivors also report restrictions in their emotional experience - a phenomenon most commonly referred to as emotional numbing. In contrast to previous accounts of posttraumatic emotional functioning our model posits that individuals with PTSD have difficulty expressing positive emotions as a result of re-experiencing states. We further argue that patients with PTSD are capable of experiencing and expressing the full range of emotions that were available pretraumatically. CONCLUSION: Our model holds that individuals with PTSD are not, in fact, 'emotionally numb' as a result of traumatic experience. Rather, PTSD is associated with hyperresponsivity to negatively valenced emotional stimuli. Consequently, patients with PTSD require more intense positive stimulation to access the full complement of appetitive or pleasant emotional behaviour.

Adult↗
PubMed2002

The gamma-secretase-generated intracellular domain of beta-amyloid precursor protein binds Numb and inhibits Notch signaling.

The beta-amyloid precursor protein (APP) and the Notch receptor undergo intramembranous proteolysis by the Presenilin-dependent gamma-secretase. The cleavage of APP by gamma-secretase releases amyloid-beta peptides, which have been implicated in the pathogenesis of Alzheimer's disease, and the APP intracellular domain (AID), for which the function is not yet well understood. A similar gamma-secretase-mediated cleavage of the Notch receptor liberates the Notch intracellular domain (NICD). NICD translocates to the nucleus and activates the transcription of genes that regulate the generation, differentiation, and survival of neuronal cells. Hence, some of the effects of APP signaling and Alzheimer's disease pathology may be mediated by the interaction of APP and Notch. Here, we show that membrane-tethered APP binds to the cytosolic Notch inhibitors Numb and Numb-like in mouse brain lysates. AID also binds Numb and Numb-like, and represses Notch activity when released by APP. Thus, gamma-secretase may have opposing effects on Notch signaling; positive by cleaving Notch and generating NICD, and negative by processing APP and generating AID, which inhibits the function of NICD.

Amyloid Precursor Protein Secretases↗
PubMed2001

Siah-1 binds and regulates the function of Numb.

The Drosophila Seven in absentia (Sina) gene product originally was described as a protein that controls cell fate decisions during eye development. Its mammalian homolog, Siah-1, recently was found to be involved in p53-dependent and -independent pathways of apoptosis and G(1) arrest. We report that Siah-1 interacts directly with and promotes the degradation of the cell fate regulator Numb. Siah-1-mediated Numb degradation leads to redistribution of endogenous cell-surface Notch to the cytoplasm and nucleus and to augmented Notch-regulated transcriptional activity. These data imply that through its ability to target Numb for degradation, Siah-1 can act as a key regulator of Numb-related activities, including Notch signaling.

Animals↗
PubMed2001

Hypnotically induced emotional numbing.

This study investigated the utility of a hypnotic suggestion to inhibit emotional response. High and low hypnotizable participants (N = 53) were administered a hypnotic induction, and half the participants were then administered a suggestion for emotional numbing. Participants were then presented with slides depicting neutral or disfigured faces. Participants who received the emotional numbing suggestion reported less responsivity to the disfigured faces than did those in the control condition, and this pattern was stronger for high than for low hypnotizable participants. Highs in the numbing condition displayed less overall distress in their facial expressions in response to the disfigured slides relative to those in the control condition. These findings suggest that hypnotic emotional numbing may be a useful paradigm in which to explore processes in emotion inhibition.

Adult↗
PubMed2005

Hypnotic emotional numbing: a study of implicit emotion.

Twenty high hypnotizable and 20 low hypnotizable participants were administered a hypnotic induction and then presented with emotionally distressing and neutral visual images. Half the participants were administered a suggestion for emotional numbing. Participants were then asked to rate the valence of neutral words that were preceded by subliminal presentations of the negative and neutral images. Whereas highs who received the emotional-numbing suggestion reported comparable ratings of the words following presentations of the negative and neutral images, highs in the control condition and lows in both conditions reported more positive ratings of words that were preceded by the negative stimuli. These findings suggest that the subliminally presented negative stimuli led participants to rate the subsequent neutral words more positively. In contrast, hypnotic emotional numbing diminished this pattern in highs. These results are discussed in terms of the influence of hypnotic emotional numbing at a preattentive stage of processing.

Adult↗
PubMed1987

Nasal tip numbness following rhinoplasty.

Inquiry into the sensory changes of the nasal tip following rhinoplasty in 75 patients showed that 65.3% experienced some degree of numbness of the nasal tip after operation. This included 29.3% who reported numbness as the only sensory change. The numbness lasted less than 3 months in 68.3% of the latter cases. Rhinoplasty involving tip reduction in particular was likely to result in postoperative numbness.

Humans↗
PubMed2004

Np9 protein of human endogenous retrovirus K interacts with ligand of numb protein X.

We have recently identified Np9 as a novel nuclear protein produced by the human endogenous retrovirus K and were able to document the exclusive presence of np9 transcript in tumors and transformed cells. With the aim of studying whether Np9 has a role in tumorigenesis, a systematic search for interacting proteins was performed. Here, we identify the RING-type E3 ubiquitin ligase LNX (ligand of Numb protein X) as an Np9-interacting partner. We furthermore show that the interaction involves N- and C-terminal domains of both proteins and can affect the subcellular localization of LNX. LNX has been reported to target the cell fate determinant and Notch antagonist Numb for proteasome-dependent degradation, thereby causing an increase in transactivational activity of Notch. We document that LNX-interacting Np9, like Numb, is unstable and degraded via the proteasome pathway and that ectopic Numb can stabilize recombinant Np9. Combined, these findings point to the possibility that Np9 affects tumorigenesis through the LNX/Numb/Notch pathway.

Animals↗
PubMed1998

The Mdm2 oncoprotein interacts with the cell fate regulator Numb.

The Mdm2 oncoprotein is a well-known inhibitor of the p53 tumor suppressor, but it may also possess p53-independent activities. In search of such p53-independent activities, the yeast two-hybrid screen was employed to identify Mdm2-binding proteins. We report that in vitro and in transfected cells, Mdm2 can associate with Numb, a protein involved in the determination of cell fate. This association causes translocation of overexpressed Numb into the nucleus and leads to a reduction in overall cellular Numb levels. Through its interaction with Numb, Mdm2 may influence processes such as differentiation and survival. This could potentially contribute to the altered properties of tumor cells which overexpress Mdm2.

Amino Acid Sequence↗