中国羊踯躅花化学成分研究

从国产杜鹃花科植物羊踯躅(Rhododendron molle G.Don)的花中分离得到两种有药理活性的成分。经光谱(IR,MS,¹HNMR,¹³CNMR,¹H-¹H COSY,¹H-¹H NOESY,¹³C-¹H COSY)等分析证明其中一种为新的四环二萜类化合物。命名为羊踯躅素Ⅲ(rhodomollein Ⅲ)(1)。     

Long-term posttreatment functioning among those treated for alcohol use disorders

This article summarizes the proceedings of a symposium that was organized and chaired by Patrick R. Clifford and presented at the 2005 Research Society on Alcoholism meeting in Santa Barbara, California. The aims of the presentation were to focus on the prediction and explanation of longer-term functioning following alcohol use disorders (AUD) treatment. Along these lines, Stephen A. Maisto, PhD, presented data (i.e., Project MATCH outpatient sample) on the relationship between drinking behavior in the first year following AUD outpatient treatment initiation and functioning at 3-year follow-up. Robert L. Stout, PhD, using data from the Extended Case Monitoring Study, analyzed long-term drinking patterns using shorter-term information. James R. McKay, PhD, examined the relationship between treatment services received and problem severities across a 2-year follow-up period. J. Scott Tonigan, PhD, served as the panel discussant.     

Training psychiatric residents in addiction

ABSTRACT

12-Step attendance is associated with increased abstinence. A strong claim made in 12-step literature is that alcoholics are pathologically selfish and that working the 12 steps reduces this selfishness, which, in turn, leads to sustained alcohol abstinence. This study tested this assumption by investigating the linkages between 12-step attendance, pathological narcissism, and drinking. One hundred thirty early Alcohol Anonymous (AA) affiliates with limited AA and treatment histories were recruited from treatment and community-based AA. A majority of the sample was alcohol dependent and reported illicit drug use before recruitment. Participants were interviewed at intake and at 3, 6, and 9 months. A majority of participants attended AA meetings throughout follow-up and such attendance predicted increased abstinence and reduced drinking intensity. 12-Step affiliates were significantly higher on pathological narcissism (PN) relative to general population samples and their PN remained elevated. Contrary to predictions, PN was unrelated to 12-step meeting attendance and did not predict later abstinence or drinking intensity. The findings did not support the hypothesis that reductions in PN explain 12-step benefit. An alternative function for the emphasis placed on pathological selfishness in 12-step programs is discussed and a recommendation is made to use unobtrusive measures of selfishness in future research.     

Differential mechanisms in the regulation of endogenous levels of thrombopoietin and interleukin-11 during thrombocytopenia: insight into the regulation of platelet production

The regulation of megakaryocytopoiesis and thrombopoiesis appears to be under the control of an array of hematopoietic growth factors. To determine the relationship of endogenous thrombopoietic cytokine levels and circulating platelet (PLT) counts, we measured the levels of thrombo-poietin (TPO), interleukin-11 (IL-11), and interleukin-6 (IL-6) in patients with significant thrombocytopenia secondary to both marrow hypoplasia and increased PLT destruction. Increased endogenous levels of TPO and IL-11, but not IL-6, were detected in bone marrow transplant patients with thrombocytopenia following myeloablative therapy (BMT/MAT) (TPO: 1,455.5 +/- 87.3 pg/mL, [PLT 39,600 +/- 7,800/microL], P < .001, n = 12; IL-11: 227.9 +/- 35 pg/mL, [PLT 32,900 +/- 57,000/microL], P < .05, n = 19; IL-6: 25.8 +/- 8.4 pg/mL, [PLT 32,800 +/- 5,057/microL], P > .05, n = 4] v normal donors [TPO < 150 pg/mL, n = 8; IL-11 < 50 pg/mL, n = 9; IL-6 < 10 pg/mL, n = 5 [PLT 203,000 +/- 7,500/microL]. There was a significant inverse correlation between endogenous levels of TPO and IL-11, but not IL-6, and PLT counts in the MAT/BMT patients (TPO: r = -0.57, P < .0001, n = 188; IL-11: r = - 0.329, P < .0001, n = 249; IL-6: r = -0.1147, P > .05, n = 62). In patients with immune thrombocytopenia purpura (ITP), with decreased PLT survival, but intact bone marrow megakaryocytopoiesis, endogenous IL-11 levels were significantly increased (328.0 +/- 92.6 pg/mL, [PLT: 20,900 +/- 3,000/microL], P < .05, n = 25). However, endogenous TPO levels remained undetectable (< 150 pg/mL, [PLT 30,500 +/- 5,500/microL], n = 15). These results suggest that there may be differential mechanisms regulating endogenous TPO, IL-11, and IL-6 levels during acute thrombocytopenia and suggest that the absolute number of circulating PLTs may not always be the sole regulator of endogenous TPO levels. Other mpl-expressing cells of the megakaryocyte lineage may contribute to the regulation of circulating TPO levels as well. Our results also suggest IL-11 levels may in part, be regulated by a negative feedback loop based on circulating PLT counts, but also may, in part, be regulated by a variety of inflammatory agonists. Both TPO and IL-11, therefore, appear to be active thrombopoietic cytokines regulating, in part, megakaryocytopoiesis during states of acute thrombocytopenia.     

Stimulation of tyrosine phosphorylation after ligation of beta7 and beta1 integrins on human B cells

B lymphocytes express several members of the integrin family of adhesion molecules that mediate cell-cell and cell-extracellular matrix interactions. In addition to beta1 integrins, predominantly alpha4 beta1, mature B cells also express alpha4 beta7, which is a receptor for vascular cell adhesion molecule-1 and fibronectin, and is also involved in the homing of B cells to mucosal sites through binding to a third ligand, mucosal address in cell adhesion molecule-1. Here we describe that crosslinking of alpha4 beta7 integrins on B cell lines and normal tonsillar B cells, induces tyrosine phosphorylation of multiple substrates of 105-130 kD, indicating that beta7 integrin plays a role as signaling molecule in B cells. This pattern of phosphorylated proteins was very similar to that induced following ligation of alpha4 beta1. Interestingly, ligation of alpha5 beta1 or alpha6 beta1 also stimulated the 105-125 kD group of phosphorylated proteins, whereas ligation of beta2 integrins did not. The focal adhesion tyrosine kinase p125FAK was identified as one of these substrates. Beta1 or beta7 mediated tyrosine phosphorylations were markedly decreased when the microfilament assembly was inhibited by cytochalasin B. These results suggest that intracellular signals initiated by different integrins in B cells may converge, to similar cytoskeleton-dependent tyrosine phosphorylated proteins.     

FcR gamma-chain is essential for both surface expression and function of human Fc gamma RI (CD64) in vivo

Most Ig receptors exist as hetero-oligomeric complexes with separate ligand binding (alpha) and signal transducing (beta, gamma, or zeta) subunits. For Fc gamma RIIIa and Fc epsilon RI, association with the FcR gamma-chain is essential for surface expression. However, the human high affinity IgG receptor, hFc gamma RI, was found to be surface- expressed by itself in transient transfection models. We have now analyzed the integrity of hFc gamma RI expression in more detail in stable transfectants. In vitro we noted that, in the absence of FcR gamma-chain, surface expression of hFc gamma RI rapidly declined to background levels, in both IIA1.6 B cells and NIH3T3 fibroblasts. The effect of FcR gamma-chain on hFc gamma RI surface expression in vivo was evaluated by using two newly generated transgenic mouse lines, selectively expressing hFc gamma RI on myeloid cells. These transgenic mice were crossed with FcR gamma-chain-deficient mice. Analysis of blood monocytes and peritoneal macrophages showed that surface expression of hFc gamma RI was reduced by approximately 80%. The remaining approximately 20% of receptors were still capable of binding IgG-opsonized RBC, suggesting FcR gamma-chain not to be critical for hFc gamma RI ligand-binding capacity. Importantly, however, hFc gamma RI signaling capacity was lost in FcR gamma-chain-deficient cells. No phagocytosis could be observed using either ligand sensitized (EA- IgG2a) or CD64-targeted erythrocytes (using a bispecific antibody) in both hFc gamma RI transgenic lines. This documents the FcR gamma-chain to be indispensable for both surface membrane expression and function of human Fc gamma RI in vivo.