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PubMedDate not supplied

Swelling, numbness, pain, and their relationship to arm function among breast cancer survivors: a disablement process model perspective.

The disablement process model proposed by Nagi in 1965 and subsequently expanded by Verbrugge and Jette was used heuristically to study the relationships among morbidities and arm/shoulder function limitations that breast cancer survivors experience in the period following treatment. A telephone survey was administered to 148 patients (67%) from among 222 breast cancer survivors who had undergone surgery in 1997 and 1998. Sixty-three percent of respondents reported experiencing some numbness, while 35% noticed swelling. Between 13% and 15% reported moderate to severe pain. Similar proportions said the occurrence of pain ranged from intermittent to constant. Between 1% and 4% reported problems with shoulder abduction and flexion and a decrease in arm strength and daily use of the arm. Swellings in the torso and arm tended to cluster into two different factors. Numbness followed a similar pattern. Apart from numbness in the arm, all the other factors had strong significant associations with one another. In multiple regression analyses, current pain intensity and swelling in the arm were independently related to current functional status of the arm/shoulder. The results suggest that it may be feasible to use patients' self-reports to develop a simple lymphedema-specific tool to monitor the functional status of women living with or at risk for lymphedema. Such a tool, if properly designed and implemented, would allow for the timely introduction of lymphedema or pain management strategies to improve arm function and ultimately the quality of life of breast cancer survivors.

Activities of Daily Living↗
PubMed1999

Distinct human NUMB isoforms regulate differentiation vs. proliferation in the neuronal lineage.

Neuronal cell fate decisions are directed in Drosophila by NUMB, a signaling adapter protein with two protein-protein interaction domains: a phosphotyrosine-binding domain and a proline-rich region (PRR) that functions as an SH3-binding domain. Here we show that there are at least four human NUMB isoforms and that these serve two distinct developmental functions in the neuronal lineage: differentiation (but not proliferation) is promoted by human NUMB protein isoforms with a type I (short) PRR. In contrast, proliferation (but not differentiation) is directed by isoforms that have a type II (long) PRR. The two types of PRR may promote distinct intracellular signaling pathways downstream of the NOTCH receptor during mammalian neurogenesis.

Alternative Splicing↗
PubMed2000

Multiple modes of peptide recognition by the PTB domain of the cell fate determinant Numb.

The phosphotyrosine-binding (PTB) domain of the cell fate determinant Numb is involved in the formation of multiple protein complexes in vivo and can bind a diverse array of peptide sequences in vitro. To investigate the structural basis for the promiscuous nature of this protein module, we have determined its solution structure by NMR in a complex with a peptide containing an NMSF sequence derived from the Numb-associated kinase (Nak). The Nak peptide was found to adopt a significantly different structure from that of a GPpY sequence-containing peptide previously determined. In contrast to the helical turn adopted by the GPpY peptide, the Nak peptide forms a beta-turn at the NMSF site followed by another turn near the C-terminus. The Numb PTB domain appears to recognize peptides that differ in both primary and secondary structures by engaging various amounts of the binding surface of the protein. Our results suggest a mechanism through which a single PTB domain might interact with multiple distinct target proteins to control a complex biological process such as asymmetric cell division.

Amino Acid Sequence↗
PubMed2004

Galloping ophthalmoplegia and numb chin in Burkitt lymphoma.

A 57-year-old man developed complete bilateral ophthalmoplegia over a period of 10 days, together with bilateral facial pain and numbness of the chin. He had no other clinical manifestations. Findings on brain magnetic resonance imaging and spinal fluid formula from the first lumbar puncture were normal, but cerebrospinal fluid flow cytometry disclosed a kappa restriction monoclonal B-cell population, indicating malignant lymphoma. Computed tomography of the chest, abdomen, and pelvis then revealed multiple enlarged lymph nodes. Biopsy of an inguinal node showed findings consistent with Burkitt lymphoma. Within six weeks, intravenous and intrathecal chemotherapy resolved all neurologic findings except a partial right-side sixth nerve palsy and mild chin numbness. Eighteen months after disease onset, the patient remained in remission. Meningeal spread of Burkitt lymphoma is not commonly a presenting feature in immunocompetent adults. Chin numbness, a characteristic feature caused by infiltration of the mental nerve, should facilitate earlier recognition, which may be life saving.

Antimetabolites, Antineoplastic↗
PubMed1998

Inscuteable and numb mediate asymmetric muscle progenitor cell divisions during Drosophila myogenesis.

Each larval hemisegment comprises approximately 30 uniquely specified somatic muscles. These derive from muscle founders that arise as distinct sibling pairs from the division of muscle progenitor cells. We have analyzed the progenitor cell divisions of three mesodermal lineages that generate muscle (and pericardial cell) founders. Our results show that Inscuteable and Numb proteins are localized as cortical crescents on opposite sides of dividing progenitor cells. Asymmetric segregation of Numb into one of the sibling myoblasts depends on inscuteable and is essential for the specification of distinct sibling cell fates. Loss of numb or inscuteable results in opposite cell fate transformations-both prevent sibling myoblasts from adopting distinct identities, resulting in duplicated or deleted mesodermal structures. Our results indicate that the muscle progenitor cell divisions are intrinsically asymmetric; moreover, the involvement of both inscuteable and numb/N suggests that the specification of the distinct cell fates of sibling myoblasts requires intrinsic and extrinsic cues.

Animals↗
PubMed2004

The soreness and numbness effect of acupuncture on skin blood flow.

The purpose of this study was to investigate the effect of the De-Qi sensations of acupuncture (sourness-distension and distension-numbness) stimulation. Fifty-two healthy medical student volunteers were given acupuncture at the Hoku (LI-4) acupoint as they were resting. During a test that lasted 30 minutes, their skin blood flow was measured at the Quchi (LI-11) acupoint and their palm temperature was measured. Our results indicated that acupuncture increased blood flow when the De-Qi sensation occurred. If the needle was twirled a few minutes thereafter and the De-Qi feeling again occurred, the same blood flow increase was seen again. If the needle was not twirled, but the test person felt soreness, numbness and heat sensation within a few minutes after needle insertion, the same blood flow increase was also seen. After acupuncture, Quchi did not show continuous increase of blood flow as did Hoku. Hoku acupuncture also increased palm temperature suggesting that the blood flow increased from cutaneous vessel vasodilation. In conclusion, when the test person felt the sore and numb De-Qi sensation, there was an increase of blood flow at the acupuncture points. Thus, our results suggest that increased flow may be one of the mechanisms accounting for meridian system responses during acupuncture.

Acupuncture Points↗
PubMed1986

The numb cheek syndrome: a sign of infraorbital neuropathy.

Three patients with skin cancer had numbness isolated to one cheek, in the distribution of the infraorbital nerve. Hypesthesia also involved the medial and lateral upper incisors and canine teeth, and adjacent gingiva, sparing the more posterior teeth and gums. The molar and premolar teeth and gums are innervated by the posterior and middle superior alveolar nerves; because these structures were spared, the pathologic process was localized to the infraorbital foramen, and we could exclude involvement of the maxillary division more proximally. In two patients, cheek numbness heralded recurrent squamous cell carcinoma. Analogous anatomy at the mental foramen should help distinguish intracranial leptomeningeal from local mandibular lesions producing isolated numbness of the chin.

Aged↗
PubMed2002

Binary cell death decision regulated by unequal partitioning of Numb at mitosis.

An important issue in Metazoan development is to understand the mechanisms that lead to stereotyped patterns of programmed cell death. In particular, cells programmed to die may arise from asymmetric cell divisions. The mechanisms underlying such binary cell death decisions are unknown. We describe here a Drosophila sensory organ lineage that generates a single multidentritic neuron in the embryo. This lineage involves two asymmetric divisions. Following each division, one of the two daughter cells expresses the pro-apoptotic genes reaper and grim and subsequently dies. The protein Numb appears to be specifically inherited by the daughter cell that does not die. Numb is necessary and sufficient to prevent apoptosis in this lineage. Conversely, activated Notch is sufficient to trigger death in this lineage. These results show that binary cell death decision can be regulated by the unequal segregation of Numb at mitosis. Our study also indicates that regulation of programmed cell death modulates the final pattern of sensory organs in a segment-specific manner.

Animals↗
PubMed2006

[Pain and numbness in the arms and hands and carpal tunnel syndrome diagnosis].

We studied the frequency and localization of pain and numbness in patients with carpal tunnel syndrome (CTS), in comparison with individuals of the general population, matched for sex and age, and we determined the sensitivity and the specificity of these symptoms for the CTS diagnosis. Pain was a common symptom in the two groups of patients. Numbness occurred more frequently in CTS group (p<0.05). In CTS patients, pain complaints were present in neck (42.8%), arms (36.8%) and hands (82.8%). Among controls, pain was more common in head (11.4%), trunk (37.1%), legs (22.8%). In our casuistics, in relation to the CTS diagnosis, the presence of pain and numbness have low sensitivity and high specificity when they occur in the arms, and high sensitivity and specificity when they occur in the hands.

Adult↗
PubMed2001

Relationship of numbing to alexithymia, apathy, and depression.

The present study assessed the relationship between numbing and three associated conditions of alexithymia, apathy, and depression, utilizing data collected on 353 Vietnam combat veterans diagnosed with Posttraumatic Stress Disorder from in- and out-patient settings and an outreach center at various Department of Veterans Affairs Medical centers. All subjects completed four self-report measures: the Glover Numbing Scale, the Beck Depression Inventory, the Apathy Evaluation Scale, and the Toronto Alexithymia Scale-20. The correlation matrix indicated that scores on the four measures were moderately to highly correlated. Principal components analysis with a varimax rotation indicated a five-factor solution that provided evidence for the factorial validity of each of the constructs assessed. Results of the factor analysis of items from the four measures were consistent with numbing being a separate and distinct construct from alexithymia, apathy, and depression. In general, results indicated that all constructs measured were separate and distinct from one another.

Affective Symptoms↗
PubMed2002

Transgenic expression of numb inhibits notch signaling in immature thymocytes but does not alter T cell fate specification.

The conserved adaptor protein Numb is an intrinsic cell fate determinant that functions by antagonizing Notch-mediated signal transduction. The Notch family of membrane receptors controls cell survival and cell fate determination in a variety of organ systems and species. Recent studies have identified a role for mammalian Notch-1 signals at multiple stages of T lymphocyte development. We have examined the role of mammalian Numb (mNumb) as a Notch regulator and cell fate determinant during T cell development. Transgenic overexpression of mNumb under the control of the Lck proximal promoter reduced expression of several Notch-1 target genes, indicating that mNumb antagonizes Notch-1 signaling in vivo. However, thymocyte development, cell cycle, and survival were unperturbed by mNumb overexpression, even though transgenic Numb was expressed at an early stage in thymocyte development (CD4(-)CD8(-)CD3(-) cells that were CD44(+)CD25(+) or CD44(-)CD25(+); double-negative 2/3). Moreover, bone marrow from mNumb transgenic mice showed no defects in thymopoiesis in competitive repopulation experiments. Our results suggest that mNumb functions as a Notch-1 antagonist in immature thymocytes, but that suppression of Notch-1 signaling at this stage does not alter gammadelta/alphabeta or CD4/CD8 T cell fate specification.

Animals↗
PubMed1992

[A case of spontaneous mediastinal emphysema developed by numbness of the left arm, dysphagia and chest pain].

A 20-year-old female developed dysphagia, chest pain and numbness of the left arm after dinner on August 22, 1990. She consulted a doctor, who diagnosed tachycardia and prescribed propranolol. On August 23, she hadn't improved. On the same day, she visited our hospital. Chest X-ray films revealed lucent band and distinct line running parallel to the border of the heart and we suspected mediastinal emphysema. Immediately we took chest CT scan, which demonstrated free air surrounding the trachea, thoracic aorta and heart. We diagnosed spontaneous mediastinal emphysema. She was treated with bed rest and mediastinal emphysema subsided within 8 days. The numbness in the patient's arm is an unusual symptom in mediastinal emphysema. We suggest that the numbness of the arm may be due to interference with the circulation to the arm by distention of the mediastinal tissue.

Adult↗
PubMed1990

Numb chin syndrome: a case report.

Neuropathy of the inferior alveolar nerve is common in dental practice. Its cause, when not a result of local anesthetic, is normally from dental disease or trauma. Isolated mental neuropathy (numb chin syndrome) is extremely uncommon, and its most common cause also is dental. The next most common cause is from an underlying neoplasm, and some cases have resulted from systemic disease (eg, multiple sclerosis). Some patients show no evidence of additional disease and experience spontaneous remission of the symptom. Numb chin syndrome cases require coordination of treatment between dentists and physicians. Since a disproportionate number of these cases present with a numb chin as the first symptom of a neoplasm, aggressive diagnosis is required. Careful follow up is important before dismissing it as a spontaneous remission. Dentists must be familiar with isolated mental neuropathy and its medical implications because they are likely to be the first health professionals that patients present to for diagnosis.

Adult↗
PubMed1987

Facial numbness and dysesthesia. New features of carotid artery dissection.

Facial numbness and dysesthesia have not been emphasized as presenting features in spontaneous internal carotid artery dissection. Progressive facial pain, accompanied by oculosympathetic paresis, altered taste, and facial numbness suggest the possibility of basal skull neoplasm. We describe a patient, with previously undiscovered fibromuscular dysplasia, who presented with severe neck and face pain, dysgeusia, oculosympathetic paresis, and markedly reduced facial sensation due to a spontaneous vascular dissection. Altered facial sensation should now be included in the symptomatology of internal carotid artery dissection.

Aortic Dissection↗
PubMed2002

Developmental changes in Notch1 and numb expression mediated by local cell-cell interactions underlie progressively increasing delta sensitivity in neural crest stem cells.

Neural stem cells become progressively less neurogenic and more gliogenic with development. Here, we show that between E10.5 and E14.5, neural crest stem cells (NCSCs) become increasingly sensitive to the Notch ligand Delta-Fc, a progliogenic and anti-neurogenic signal. This transition is correlated with a 20- to 30-fold increase in the relative ratio of expression of Notch and Numb (a putative inhibitor of Notch signaling). Misexpression experiments suggest that these changes contribute causally to increased Delta sensitivity. Moreover, such changes can occur in NCSCs cultured at clonal density in the absence of other cell types. However, they require local cell-cell interactions within developing clones. Delta-Fc mimics the effect of such cell-cell interactions to increase Notch and decrease Numb expression in isolated NCSCs. Thus, Delta-mediated feedback interactions between NCSCs, coupled with positive feedback control of Notch sensitivity within individual cells, may underlie developmental changes in the ligand-sensitivity of these cells.

Animals↗
PubMed1987

Lingual numbness and speech articulation deviation associated with temporomandibular joint disk displacement.

A prospective investigation of 208 patients with painful, arthrographically verified temporomandibular joint disk displacement revealed that seven patients (3%) demonstrated lingual numbness associated with speech articulation impairment. The speech disorder was characterized primarily by a distortion in the production of /s,r,d, and t/. The lingual numbness and the speech disorder had in all cases started in association with a painful onset of permanent displacement of the temporomandibular joint disk. Local anesthetic blocking of the auriculotemporal nerve eliminated both joint pain and muscle pain and normalized tongue sensitivity and speech articulation. Placebo injections of saline solution resulted in no change. The explanation of the phenomenon is that the course of the lingual nerve for these seven patients was through the lateral pterygoid muscle rather than mesial to the muscle bundles and that an arthrokinetic myospasm resulted in compression of the lingual nerve. In order to test the hypothesis that the condition of lingual nerve entrapment in the lateral pterygoid muscle does exist, the course of the nerve was studied at dissection in 52 specimens from 26 cadaver heads. In 49 of the specimens, the lingual nerve descended deep to the lateral pterygoid muscle as has been traditionally defined. However, in three specimens, the nerve passed through the inferior belly of the muscle, revealing the condition of lingual nerve entrapment.

Adult↗
PubMed2005

Selective numbing and hyperarousal in male and female Bosnian refugees with PTSD.

Emotional numbing is an important symptom of PTSD, but it is not clear whether it affects both positive and negative affect equally or not. To address this question we administered Lang's Looking at Pictures test, in which a series of pictures are rated for valence (pleasant-unpleasant) and arousal (high-low), to 10 male and 11 female Bosnian refugees suffering from PTSD (DSM-IV criteria) and to control groups of 11 male and 10 female Bosnian refugees with similar trauma exposure but without PTSD or any other major mental illness. The mean valence ratings for unpleasant, neutral, and pleasant pictures of both PTSD and control males and females were similar to normal ratings. Likewise, the mean arousal ratings for unpleasant, neutral, and pleasant pictures of both male and female controls were similar to normals, with both unpleasant and pleasant pictures rated more arousing than neutral pictures. In contrast, in both males and females with PTSD pleasant pictures were rated as almost completely non-arousing. Thus, in Bosnian refugees affective numbing is seen primarily with pleasant or positive stimuli.

Adult↗
PubMed2003

Mammalian Numb is a target protein of Mdm2, ubiquitin ligase.

Drosophila Numb protein functions as an antagonist against Notch signal. The expression of this protein is asymmetrical in divided cells and thought to be involved in the neural cell differentiation and/or cell fate. Human homologue of Numb (hNumb) was cloned as Mdm2-binding protein by yeast two-hybrid screening. Since Mdm2 is an oncoprotein and has ubiquitin ligase activity toward tumor suppressor p53, we assessed to find out whether Mdm2 ubiquitinylates the hNumb protein. The recombinant hNumb expressed in Sf-9 cells using baculovirus protein expression system bound to Mdm2 in vitro. When hNumb was subjected to in vitro ubiquitinylation assay system, which contains E1, E2, or UbcH5c, and Mdm2, hNumb was ubiquitinylated as efficiently as the p53 protein. However, when the Ring-finger domain mutant of Mdm2 was used in place of wild-type Mdm2, hNumb was not ubiquitinylated. Furthermore, when U2OS cells were co-transfected with hNumb and Mdm2, the hNumb protein was ubiquitinylated and degraded. These data strongly suggest that Mdm2 functions as the ubiquitin ligase toward hNumb and that it induces its degradation in intact cells.

Animals↗