The B-cell transmembrane protein CD72 binds to and is an in vivo substrate of the protein tyrosine phosphatase SHP-1

BACKGROUND: Signals from the B-cell antigen receptor (BCR) help to determine B-cell fate, directing either proliferation, differentiation, or growth arrest/apoptosis. The protein tyrosine phosphatase SHP-1 is known to regulate the strength of BCR signaling. Although the B-cell co-receptor CD22 binds SHP-1, B cells in CD22-deficient mice are much less severely affected than those in SHP-1-deficient mice, suggesting that SHP-1 may also regulate B-cell signaling by affecting other signaling molecules. Moreover, direct substrates of SHP-1 have not been identified in any B-cell signaling pathway. RESULTS: We identified the B-cell transmembrane protein CD72 as a new SHP-1 binding protein and as an in vivo substrate of SHP-1 in B cells. We also defined the binding sites for SHP-1 and the adaptor protein Grb2 on CD72. Tyrosine phosphorylation of CD72 correlated strongly with BCR-induced growth arrest/apoptosis in B-cell lines and in primary B cells. Preligation of CD72 attenuated BCR-induced growth arrest/death signals in immature and mature B cells or B-cell lines, whereas preligation of CD22 enhanced BCR-induced growth arrest/apoptosis. CONCLUSIONS: We have identified CD72 as the first clear in vivo substrate of SHP-1 in B cells. Our results suggest that tyrosine-phosphorylated CD72 may transmit signals for BCR-induced apoptosis. By dephosphorylation CD72. SHP-1 may have a positive role in B-cell signaling. These results have potentially important implications for the involvement of CD72 and SHP-1 in B-cell development and autoimmunity.     

The role of splenectomy in treating severe aplastic anemia

A hypotensive effect of clonidine in non-narcotized intact and aorta baro-denervated rats is studied under conditions of minimization of stress actions (radiotelemetry) and under standard conditions of direct recording arterial pressure (AP). Direct AP recording is shown to determine an increase in background AP in baro-denervated rats, but not in control rats. An increase in background AP level under conditions of direct recording is not accompanied with decreasing hypotensive effect of clonidine in baro-denervated rats.     

Anesthetic management and perioperative surveillance

The intraoperative management of the high-risk patient has received a great deal of attention and research during the past decade. Based on the available evidence, there appears to be no one best anesthetic technique or agent. More importantly, the goals of intraoperative management are to avoid myocardial ischemia, which include preventing tachycardia, and maintaining normothermia and adequate hematocrit. Perioperative monitoring includes transesophageal echocardiography, pulmonary artery catheter and ST segment monitoring. Perioperative pharmacological treatment with alpha-2 agonists and beta-adrenergic blocking agents are associated with a reduced incidence of perioperative myocardial ischemia and improved long-term survival, respectively. Future research will be required to determine whether prophylactic therapy or early treatment of perioperative myocardial ischemia will lead to improved outcome.     

Comments on "Measuring memory for source: Some theoretical assumptions and technical limitations"

Three studies showed that information used in determining a target memory's source may be derived not only from the target event itself, but also from other nontarget events or memories. Subjects were more likely to claim that an imagined object was perceived when it physically resembled or was conceptually related to another specific item that was actually perceived, relative to when there was no physical resemblance or semantic relation. Furthermore, error rates for imagined items increased with the number of perceived items that they resembled. However, subjects' orienting task at encoding (perceptually biased or perceptually plus conceptually biased) did not systematically affect error rates. The results indicate that reality monitoring decisions about a target object are influenced by similar physical and conceptual information that was derived from other objects.     

A light and electron microscopic study of cytoplasmic phospholipase A2 and cyclooxygenase-2 in the hippocampus after kainate lesions

Tamoxifen, the major adjuvant drug treatment for estrogen-dependent breast cancer, has been shown previously to affect both estrogen-dependent and calcium/calmodulin-dependent pathways. In the current study, we developed an in vitro slice system to study the effects of tamoxifen on ATP levels in hypothalamic (HTH) and preoptic areas (POA) of the rat brain. Baseline data showed that, following a 2-h incubation, HTH and POA slices had comparable ATP levels to hippocampal slices, a system used extensively by researchers examining the metabolic responsiveness of the hippocampal region (HPC) of the brain. HTH-POA slice ATP levels remained steady for 2, 4 and 6 h, but fell to 11% of initial levels by 12 h. Neurons from HTH-POA slices incubated for 4 h appeared healthy and demonstrated robust protein synthesis as measured autoradiographically by incorporation of [3H]leucine. We explored the effects of tamoxifen (TAM), fluphenazine (FLU) and estradiol (E2) on ATP levels in HTH and POA slices. The effects of TAM were complex: a 4-h incubation with 10-6 M TAM led to decreased ATP levels in HTH (but not POA), and a 4-h incubation with 10-8 M led to increased ATP levels in POA (but not HTH); a 15-min exposure to 10-6 M TAM decreased ATP levels in POA (but not HTH) slices, while the exposure of slices to the lower concentration of TAM was without effect in either area. As with higher concentrations of TAM, 4-h incubation with 10-6 M FLU decreased ATP levels in HTH (but not POA), while incubation with E2 did not affect slice ATP levels. These data are consistent with the hypothesis that both TAM and FLU alter ATP levels in HTH slices via calmodulin- or calcium-mediated processes.