Anti-NUMB monoclonal antibody Made to order

Mental nerve neuropathy is usually due to local trauma or dental causes, but may be a manifestation of malignancy. A patient with virologically controlled human immunodeficiency virus (HIV) infection presented with a numb chin' on the background of long-standing night sweats, malaise and weight loss, worsening respiratory symptoms, and lymphadenopathy. Burkitt non-Hodgkin lymphoma was diagnosed from histology of a lymph node. Imaging (magnetic resonance imaging and (18)fluorodeoxyglucose [FDG]-positron emission tomography-computed tomography [PET-CT]) showed abnormal intracranial enhancement of the right mandibular nerve and extensive (18)FDG-avid lymphadenopathy above and below the diaphragm, focal lesions in the spleen and within the right mandible. The patient received chemotherapy and remains in clinical and radiological remission seven years later. This case highlights the need for clinicians to maintain a high index of suspicion for underlying malignancy when an HIV-infected patient presents with new onset of a numb chin'. Additionally, it demonstrates the importance of functional (18)FDG-PET-CT and neuroimaging in order to identify site(s) of pathology.

The asymmetric inheritance of NUMB during mitosis determines future daughter cell fates in multiple model organisms. NUMB asymmetric inheritance has also been postulated for hematopoietic stem cell (HSC) divisions but remained controversial until recently. To reconcile conflicting reports, we revisited the evidence for asymmetric inheritance of NUMB during HSC divisions. We demonstrate that previously used strategies to identify dividing cells in fixed samples suffer from multiple systematic errors. Nonmitotic cells in close proximity are frequently mistaken as dividing cells, while mitotic cells are not detected. Furthermore, microtubule depolymerization by either nocodazole or low temperatures prevents the reliable detection of mitosis and introduces mitotic artifacts. Without artificial microtubule depolymerization and by the use of reliable mitotic markers, we find NUMB differences in daughter cells to be reduced and restricted to cells with low NUMB expression and thus low signal over background. This bias fits the expected random distribution of simulated noise data, suggesting that the putative asymmetric inheritance of NUMB in HSCs could be merely technical noise. We conclude that functionally relevant asymmetric inheritance of NUMB and other factors in mitotic HSCs and other cells cannot be conclusively demonstrated using snapshot data and requires alternative approaches, such as continuous quantitative single-cell analysis.