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PubMed2003

Numb and Numblike control cell number during vertebrate neurogenesis.

A fundamental problem in nervous system development is how to control progenitor-cell divisions to generate the correct number of cells for the mature brain and spinal cord. A recent report by Petersen and colleagues has identified an essential role for Numb and a related protein, Numblike, in this process. This study demonstrates that Numb and Numblike function to maintain the self-renewal properties of neural progenitor cells in the vertebrate neural tube.

Animals↗
PubMed1996

Posterior skin flap numbness after total hip arthroplasty.

The results of a study into posterior skin flap numbness in 25 scars following primary hip arthroplasty using a straight lateral incision are reported. Nineteen scars (76%) examined were found to have some degree of skin flap numbness. In none of these patients, however, was it considered to be a significant problem. This is believed to be the first description of this neurologic problem following this approach to total hip arthroplasty and that patients should be advised of it before surgery.

Aged↗
PubMed2003

Theoretical and empirical exploration of the similarities between emotional numbing in posttraumatic stress disorder and alexithymia.

This study rationally and scientifically examines the similarities between the emotional numbing symptoms of posttraumatic stress disorder (PTSD) and alexithymia. A clinical database from the Iowa City Department of Veterans Affairs Medical Center consisting of data from 274 combat veterans was used. Significant positive correlations were found between measures of PTSD, alexithymia, and combat exposure. Principal components analysis supported a lack of independence between PTSD subscales and alexithymia, as all variables loaded on one factor best labeled PTSD. This article presents both theoretical and empirical evidence suggesting that in traumatized persons, alexithymia may be better conceptualized as the emotional numbing aspect of PTSD rather than as a distinct construct.

Adult↗
PubMed1998

Mesodermal cell fate decisions in Drosophila are under the control of the lineage genes numb, Notch, and sanpodo.

In Drosophila, much has been learned about the specification of neuronal cell fates but little is known about the lineage of mesodermal cells with different developmental fates. Initially in development, individual mesodermal precursor cells are singled out to become the founder cells for specific muscles. The selection of muscle founder cells is thought to employ a Notch-mediated process of lateral inhibition, similar to what is observed for the specification of neural precursors. These muscle founder cells then seem to fuse with the surrounding, uncommitted myocytes inducing the formation of muscle fiber syncytia. In contrast, the differentiated progeny of neural precursor cells are usually the result of a fixed pattern of asymmetric cell divisions which are directed, in part, by interactions between numb, a localized intracellular-receptor protein, sanpodo (spdo), a potential tropomodulin homolog, and Notch, a transmembrane receptor protein. Here, we have investigated the role of these neural lineage genes in the cell fate specification of muscle and heart precursors. In particular, we have focused on a progenitor cell that is likely to produce a mixed lineage, generating both a pericardial heart cell and a somatic muscle founder cell. We show that the asymmetric segregation of Numb into one of these daughter cells antagonizes the function of Notch and spdo by preventing the presumptive muscle founder from assuming the same fate as its cardiac sibling. Our results suggest that asymmetric cell divisions, in addition to the previously-documented inductive mechanisms, play a major role in cardiac and somatic muscle patterning and that additionally the cytoskeleton may have a role in the asymmetrical localization of cell fate determinants.

Animals↗
PubMed1997

Numb chin syndrome as an initial symptom of acute lymphocytic leukemia: report of three cases.

This article describes three cases of acute lymphocytic leukemia that presented with mental neuropathy, or so-called "numb chin syndrome," as the initial symptom of the disease. This symptom heralded the initial progression of the disease in the first and second cases and the recurrence of the disease in the third case. In these cases tenderness in the mental foramen, percussion pain of the teeth, loosening and extrusion of the teeth, and radiographic abnormalities were also, if not always, observed in association with mental neuropathy. The radiographic abnormalities included a disappearance of the mandibular canals, an enlarged periodontal ligament space, a loss or thinning of the lamina dura, and a destruction of the alveolar crestal bone. This report indicates that oral manifestations can therefore occasionally play an extremely important role in the early recognition of acute lymphocytic leukemia. The unexplained oral abnormalities such as numbness of the chin and lower lip must thus be considered, potentially ominous indication of acute lymphocytic leukemia.

Adolescent↗
PubMed1999

Modes of protein movement that lead to the asymmetric localization of partner of Numb during Drosophila neuroblast division.

Partner of Numb (Pon) colocalizes with the determinant Numb and is required for its proper asymmetric localization in Drosophila. How the asymmetric localization of Pon is accomplished is not well understood. Here, we show that Pon localization takes place at the protein level and that its C-terminal region is necessary and sufficient for asymmetric localization. Fusion of the Pon localization domain with green fluorescent protein (GFP) allowed monitoring of the localization process in living embryos. Upon a neuroblast's entry into mitosis, Pon is recruited from the cytoplasm to the cortex. Cortically recruited Pon can move apically or basally within the two-dimensional confines of the cortex. This movement can occur when myosin motor activity is inhibited. However, the restriction of Pon to the basal cortex requires both actomyosin and Inscuteable.

Animals↗
PubMed2002

Numb: "Adapting" notch for endocytosis.

During sensory organ precursor divisions in Drosophila, the numb gene product segregates asymmetrically into one of the two daughter cells, to which it confers a specific fate by inhibiting Notch signaling. In this issue of Developmental Cell, Berdnik et al. show that Numb recruits alpha-Adaptin and that this physical interaction plays a role in downregulating Notch, presumably by stimulating endocytosis of Notch.

Animals↗
PubMed2005

Facial numbness in a man with inguinal and retroperitoneal masses.

BACKGROUND: A 37-year-old Brazilian man was admitted to Massachusetts General Hospital for evaluation of left-sided facial numbness, left-sided ataxia, dizziness, and vertigo. Seven weeks prior to admission, he reported numbness of the left oral cavity and tongue after a dental procedure. Three weeks prior to presentation, he developed left-sided incoordination with dizziness and vertigo. One week later, he noticed difficulty using a box cutter at work and presented to the emergency department for evaluation. A CT scan without contrast revealed no abnormalities and he was discharged home. Three days prior to admission, the patient developed diplopia. Cranial MRI revealed a 1.6 cm irregular enhancing mass in the left middle cerebellar peduncle. Neurologic examination was significant for diminished sensation over the left face to pinprick, left-sided dysmetria, and mild lateral instability of the trunk while walking. INVESTIGATIONS: MRI, lumbar puncture, CT scans of the abdomen and pelvis, needle biopsy of the lymph node, and paraneoplastic antibodies. DIAGNOSIS: Possible paraneoplastic demyelination. MANAGEMENT: Orchiectomy, adjuvant radiation, and corticosteroids.

Adult↗
PubMed2002

Asymmetric segregation of Numb: a mechanism for neural specification from Drosophila to mammals.

It is a major challenge to understand how the neuroepithelial cells of the developing CNS choose between alternative cell fates to generate cell diversity. In invertebrates such as Drosophila melanogaster and Caenorhabditis elegans, asymmetric segregation of cell-fate determining proteins or mRNAs to the two daughter cells during precursor cell division plays a crucial part in cell diversification. There is increasing evidence that this mechanism also operates in vertebrate neural development and that Numb proteins, which function as cell-fate determinants during Drosophila development, may also function in this way in vertebrates. Recent studies on mouse cortical progenitor cells have provided the strongest evidence yet that this is the case. Here, we review these and other findings that suggest an important role for the asymmetric segregation of Numb proteins in vertebrate neural development.

Animals↗
PubMed2000

'Numbness of the feet' is a poor indicator for polyneuropathy in Type 2 diabetic patients.

AIMS: To identify neuropathic sensory symptoms associated with a clinical neurological examination (CNE) and to investigate whether these symptoms could be used as a diagnostic or screening tool for diabetic polyneuropathy in general practice. METHODS: Five hundred and eighty-eight patients with Type 2 diabetes, recruited from 26 general practices in the Netherlands, underwent a CNE and completed a diabetes symptom checklist that included 10 items on neuropathic sensory symptoms. Linear regression analyses were performed to assess the association between neuropathic symptoms and CNE. Receiver operating characteristic (ROC) curves were created to assess the diagnostic properties of neuropathic symptoms. RESULTS: In this population, with a mean age of 66.8 years, 32% were identified with diabetic polyneuropathy according to the CNE. Variables that showed the strongest association with CNE score were age (beta = 0.41), symptoms of sensory alteration (beta = 0.27), and the item 'numbness of the feet' (beta = 0.35) in particular. ROC curves showed that prediction of diabetic polyneuropathy from these symptoms was unsatisfying. The sensitivity and specificity of daily symptoms of 'numbness of the feet' were 28% and 93%, respectively, in patients <68 years, and 22% and 92%, respectively, in patients > or =68 years. CONCLUSIONS: Identification of neuropathic sensory symptoms is not useful as a diagnostic or even a screening tool in the assessment of diabetic neuropathy in daily practice. Therefore, the results reported in this paper mandate an annual foot examination by the general practitioner.

Aged↗
PubMed2002

The Coxsackievirus and adenovirus receptor (CAR) forms a complex with the PDZ domain-containing protein ligand-of-numb protein-X (LNX).

The Coxsackievirus and adenovirus receptor (CAR) functions as a virus receptor, but its primary biological function is unknown. A yeast two-hybrid screen was used to identify Ligand-of-Numb protein-X (LNX) as a binding partner to the intracellular tail of CAR. LNX harbors several protein-protein interacting domains, including four PDZ domains, and was previously shown to bind to and regulate the expression level of the cell-fate determinant Numb. CAR was able to bind LNX both in vivo and in vitro. Efficient binding to LNX required not only the consensus PDZ domain binding motif in the C terminus of CAR but also upstream sequences. The CAR binding region in LNX was mapped to the second PDZ domain. CAR and LNX were also shown to colocalize in vivo in mammalian cells. We speculate that CAR and LNX are part of a larger protein complex that might have important functions at discrete subcellular localizations in the cell.

Animals↗
PubMedDate not supplied

Numb chin syndrome in Ewing sarcoma.

The numb chin syndrome consists of unilateral hypesthesia of the chin and lower lip. In adults, it is often associated with metastatic disease to the mandible, base of the skull, or leptomeninges. In children, it has been associated with infiltration of the inferior alveolar nerve by leukemic cells. We describe two cases of numb chin syndrome in children with Ewing sarcoma. In a child with a solid tumor, this symptom seems to have an ominous meaning and should lead to the investigation of progressive skeletal involvement.

Adolescent↗
PubMedDate not supplied

The numb chin syndrome as an early manifestation of giant-cell (temporal) arteritis: a case report.

We describe a 70-year-old woman with a 2-month history of a numb chin and gradually increasing bilateral headache and malaise. Neurological examination disclosed chin hypoesthesia while investigations showed a normocytic anemia, ESR of 100, and CRP of 72. A CT brain scan, chest X-ray, and bone scan showed no evidence of malignancy. Temporal arteritis was suspected and prednisolone started with prompt resolution of the headache, chin hypoesthesia, ESR, and CRP. This case illustrates an unusual etiology of the numb chin syndrome, which in most occasions is associated with malignancy. Temporal arteritis should be borne in mind as a possible explanation for this as it is a treatable condition with potentially serious, life-threatening complications.

Aged↗
PubMed1992

"Numb, clumsy hands" and tactile agnosia secondary to high cervical spondylotic myelopathy: a clinical and electrophysiological correlation.

Four patients presented with a distinctive syndrome of "numb, clumsy hand" and tactile agnosia. Myelography and computed tomographic myelography (CTM) of the cervical spine documented major spondylotic compressive lesions mainly between the C3 and C5 levels. The cortical responses of dermatomal somatosensory evoked potentials (DSEPs) revealed progressively prolonged peak latencies and progressively decreased amplitudes of early components from C6 to C8 dermatomal stimulation. In comparison, the C5 and L2 DSEPs were affected to a lesser extent. This finding suggests that high cervical cord compression may produce dysfunction of the dorsal column caudal to the direct compressive sites. In other words, the funiculus cuneatus of C6-8 cord is most affected in high cervical myelopathy. Moreover, the funiculus cuneatus is within the border zone susceptible to an overall reduction in blood flow. We conclude therefore, that ischemia secondary to cord compression is the pathophysiology resulting in this unique syndrome of "numb, clumsy hands" and tactile agnosia.

Aged↗
PubMed1992

Herald facial numbness.

Three unusual patients who developed subacute facial numbness as the heralding symptom of an expanding tumor that involved the trigeminal nerve fibers are reported. The first patient had clinical and electrophysiological evidence of an isolated mental neuropathy as a result of metastatic lesions with bone destruction from a renal cell carcinoma. The second patient had a sensorimotor trigeminal neuropathy caused by a direct compression of the semilunar ganglion by a cavernous hemangioma of Meckel's cave. The last patient experienced facial numbness as the unusual presenting manifestation of a primary brainstem lymphoma. Patients 1 and 3 died a few weeks after the admission, whereas patient 2 poorly recovered. Despite the availability of new techniques for early diagnosis, this report demonstrates how difficult it can initially be to differentiate a 'benign' trigeminal neuropathy from serious conditions and underscores the poor prognosis of fifth nerve fibers involvement by an expanding mass. Early referral with clinical and electrophysiological evaluation appears to be of crucial importance.

Adult↗
PubMed2000

Alternate numbness in the upper extremities as the initial symptom of basilar migraine: an electrophysiological evaluation using EEG power topography.

A case of basilar migraine (BM) with alternate numbness as the initial symptom is described. The patient's chief complaint was alternate numbness in the right and left upper extremities. After angiography the patient fell into a drowsy state, followed by excitation, and finally confusion. The EEG power topography showed slow alpha, theta and delta power in the right occipital area, and alternatively in the right and left parietal area. These findings suggest that the cause of BM is not only based on a vasoconstriction mechanism, but also cortical spreading depression. BM should be suspected as a cause of sensory symptoms.

Adolescent↗
PubMed1998

Lower lip numbness due to peri-radicular dental infection.

Lower lip numbness has always been a sinister symptom. Much has been written about it being the sole symptom of pathological lesions and metastatic tumours in the mandible. It may also be a symptom of manifestations of certain systemic disorders. A case of lower lip numbness resulting from the compression of the mental nerve by a peri-radicular abscess is presented because of the unusual nature of this spread of infection.

Emergency Medical Services↗