Anti-Abl (mutation Y253H) Monoclonal Antibody, clone XH001

Trigeminal neuralgia is a common neuropathic pain in the head and face. The pathogenesis of trigeminal neuralgia is complex, and so far, the pathogenesis of trigeminal neuralgia involving peripheral and central nervous inflammation theory has not been explained clearly. The loss of dopamine neurons in striatum may play an important role in the development of trigeminal nerve, but the reason is not clear. C-Abl is a nonreceptor tyrosine kinase, which can be activated abnormally in the environment of neuroinflammation and cause neuron death. We found that in the rat model of infraorbital nerve ligation trigeminal neuralgia, the pain threshold decreased, the expression of c-Abl increased significantly, the downstream activation product p38 was also activated abnormally and the loss of dopamine neurons in striatum increased. When treated with imatinib mesylate (STI571), a specific c-Abl family kinase inhibitor, the p38 expression was decreased and the loss of dopaminergic neurons was reduced. The mechanical pain threshold of rats was also improved. In conclusion, c-abl-p38 signaling pathway may play an important role in the pathogenesis of trigeminal neuralgia, and it is one of the potential targets for the treatment of trigeminal neuralgia.

A model of post-diagnosis chronic myeloid leukemia (CML) dynamics across treatment cessations is applied here to pre-diagnosis scenarios of A-bomb survivors. The main result is that perturbing two parameters of a two-state simplification of this model captures the essence of two A-bomb survivor mysteries: (1) in those exposed to > 1 Sv in Hiroshima, four of six female onsets arose as a cluster in 1969-1974, well after 5-10-year latencies expected and observed in two of six female- and nine of ten male cases (about one background case was expected in this high-dose cohort); and (2) no Nagasaki adult cases exposed to > 0.2 Sv were observed though about nine were expected (similar to 1.5 background + similar to 7.5 radiation-induced). Overall, it is concluded that: (1) whole-body radiation co-creates malignant and benign BCR-ABL clones; (2) benign clones are more likely to act as anti-CML vaccines in females than in males; (3) the Hong Kong flu of 1968 (and H3N2 seasonal flu thereafter) exhausted anti-CML immunity, thereby releasing radiation-induced clones latent in high-dose Hiroshima females; and (4) benign cells of 1-2 are CD4(+) as human T-cell leukemia-lymphoma virus-1 endemic to Nagasaki but not Hiroshima expands numbers of such cells. The next goal is to see if these conclusions can be substantiated using banked A-bomb survivor blood samples.