Demonstration of a leukemia-associated antigen (CAMAL) in peripheral blood leucocytes of bone marrow transplant patients prior to relapse

We have previously described a monoclonal antibody (CAMAL-1) that reacts in an indirect immunoperoxidase slide test at high frequency with cells of patients with acute nonlymphoblastic leukemia (ANLL), both at presentation and in remission (1). This article reports on a 12-month blind study carried out on peripheral blood leukocytes (PBL) of patients who had received bone marrow transplants for acute leukemias. PBL of patients attending the Royal Marsden Hospital were sent as cytospins to the University of British Columbia for staining and screening. Results of this study showed the following: of the 15 patients who remained in remission during the period of the study, 13 showed no abnormal increase in reactivity with CAMAL-1 (2 patients did show increased levels of reactivity over time); of the four patients relapsing but surviving within this period with ANLL, all showed elevated numbers of cells reactive with CAMAL-1 as long as 3 months prior to relapse (the two relapsing patients who had acute undifferentiated leukemia and acute lymphoblastic leukemia did not show elevations of CAMAL-1-reactive cells); of the 14 patients dying during this time of causes other than leukemia, none had elevated levels of CAMAL-1-reactive cells--and, of 4 patients dying in relapse, all had extremely elevated levels of CAMAL-1-reactive cells as long as 4 months prior to relapse. The implications of these observations are discussed.     

大花紫玉盘中新多氧取代环己烯类的结构鉴定

从番荔枝科紫玉盘属植物大花紫玉盘( Uvaria grandiflora Roxb.)根茎中分得4种新的多氧取代环己烯及已知化合物zeylenol,应用波谱分析、X-射线衍射、园二色谱和 Mosher 酯制备等手段确定了全部新化合物的结构及其绝对构型,分别命名为大花紫玉盘醇A(1),B(2),E(3)和F(4)。     

Mutant HSPB1 overexpression in neurons is sufficient to cause age-related motor neuronopathy in mice

The small heat shock protein HSPB1 is a multifunctional, α-crystallin-based protein that has been shown to be neuroprotective in animal models of motor neuron disease and peripheral nerve injury. Missense mutations in HSPB1 result in axonal Charcot-Marie-Tooth disease with minimal sensory involvement (CMT2F) and distal hereditary motor neuropathy type 2 (dHMN-II). These disorders are characterized by a selective loss of motor axons in peripheral nerve resulting in distal muscle weakness and often severe disability. To investigate the pathogenic mechanisms of HSPB1 mutations in motor neurons in vivo, we have developed and characterized transgenic PrP-HSPB1 and PrP-HSPB1(R136W) mice. These mice express the human HSPB1 protein throughout the nervous system including in axons of peripheral nerve. Although both mouse strains lacked obvious motor deficits, the PrP-HSPB1(R136W) mice developed an age-dependent motor axonopathy. Mutant mice showed axonal pathology in spinal cord and peripheral nerve with evidence of impaired neurofilament cytoskeleton, associated with organelle accumulation. Accompanying these findings, increases in the number of Schmidt-Lanterman incisures, as evidence of impaired axon-Schwann cell interactions, were present. These observations suggest that overexpression of HSPB1(R136W) in neurons is sufficient to cause pathological and electrophysiological changes in mice that are seen in patients with hereditary motor neuropathy.