Monocyte-Dependent Costimulatory Effect of TGF-β1 on Rat T-Cell Activation

TGF-β1 is known to have suppressive effects on both T-cell proliferation and effector functions, but costimulatory effects have also been reported. In the present investigation the effect of TGF-β1 is studied in vitro on T-cell proliferative responses of rat spleen cells and of lymph node cells to alloantigens (MLR), the superantigen Staphylococcal enterotoxin A (SEA) or IL-2. Without addition of TGF-β1, adherent, freshly isolated rat spleen monocytes have a suppressive effect on T-cell activation, which upon addition of TGF-β1 is reversed to a strong costimulatory effect. The costimulatory effect of TGF-β1 is shown to be entirely dependent on the presence of fresh monocytes. Costimulation is demonstrated when TGF-β1 is added to spleen cells at the start of the in vitro assays but not when added more than 24 h after the start. Costimulation is not demonstrable when TGF-β1 is added to lymph node cells alone but is readily detectable after admixture of freshly isolated spleen monocytes to the lymph node cells. TGF-β1 added at the end of culture induces suppression of T-cell activation irrespective of the presence or absence of monocytes. When TGF-β1 is added both at the start of an MLC and again after 4 days, the costimulatory effect is maintained, although somewhat moderated. The costimulatory effect of TGF-β1 is demonstrated as an increase of the T blast cell population of both CD4⁺ IL-2R⁺ and CD8⁺ IL-2R⁺ T-cell subsets, whereas the suppressive effect of TGF-β1 is shown as reduction of the same parameters.     

蛇足石杉生物碱成分的研究

从石杉科植物蛇足石杉中分离出三个生物碱(Ⅰ～Ⅲ)。经光谱数据和衍生物的制备证明:生物碱(Ⅰ)和(Ⅲ)分别为石杉碱乙(Ⅰ)和N-甲基石杉碱乙(Ⅲ);生物碱(Ⅱ)为新化合物,命名为蛇足石杉碱(huperzinine)。本文报告碱(Ⅱ)的结构测定。(Ⅱ)的生物活性正在研究中。     

你是彩妆“情敌”吗？

要做一个彩妆至上的“好色”女人，还是一个清爽、无瑕的气质女人，就要看看你的肌肤是否是天生的彩妆“情敌”了。[编者按]     

Induced abortion is not a cause of subsequent preterm delivery in teenage pregnancies

To examine the possible impact of previous induced abortion on the occurrence of preterm delivery in the subsequent pregnancy in teenage women, a retrospective case-control study was performed on mothers aged 13-19 years who delivered in one tertiary hospital over a 4 year period. Those who had a history of induced abortion prior to the index pregnancy were identified from the records and compared with a control group without previous induced abortion and who were matched for maternal age and parity. Of the 118 cases thus identified, 28 (23.7%) had more than one induced abortions and 18 (15.3%) had one or more induced abortions in the second trimester. There were 10 (8.5%) para 1 cases. No significant differences could be demonstrated between the study and control groups in the maternal demographics, major pregnancy complications, or perinatal outcome, except for the incidence of smokers which was significantly higher (39.0 versus 14.4%, P < 0.02) in the study group. The number of previous induced abortions did not appear to be related to the incidence of preterm labour, which was 10.2 and 8.5% in the study and control groups respectively. Our findings indicate that previous induced abortion is not a significant cause of preterm labour and delivery in teenage pregnancies.      

Prognostic factors for an unsatisfactory primary methotrexate treatment of cervical pregnancy: a quantitative review

To determine the risks when the primary methotrexate (MTX) treatment of cervical pregnancy has an unsatisfactory outcome, we conducted a Medline search on relevant literature published from January 1983 to June 1997. The search yielded 28 publications of 48 cases of cervical pregnancy. These and four new cases from our institutions were used in our study. A cervical pregnancy that presented with a serum beta-human chorionic gonadotrophin concentration of > or = 10,000 mIU/ml [odds ratio (OR) 10.82, 95% confidence interval (CI) 2.59, 45.14], gestational age at > or = 9 weeks (OR 6.44, 95% CI 1.46, 28.52), embryonic cardiac activity (OR 14.29, 95% CI 2.95, 76.92), and crown- rump length of >10 mm (OR 13.33, 95% CI 1.46, 120.48) was considered to be associated with a higher unsatisfactory rate of primary MTX treatment. A concomitant feticide was found to enhance the therapeutic effect of MTX treatment if embryonic cardiac activity was evident (OR 0.13, 95% CI 0.02, 0.68). Administration of a high dose of MTX did not seem to be more effective than a lower one. Our findings supported some previous observations and, more importantly, provided useful clinical information in selecting appropriate candidates for MTX treatment in cases of cervical pregnancy.      

Endothelium dependence of prostanoid-induced relaxation in human hand veins

The endothelium dependence of prostanoid-induced relaxation was examined in human isolated hand veins precontracted by endothelin. Indomethacin (10^-6 mol l^-1) and the thromboxane A₂-receptor antagonist BM 13.505 (10^-6 mol l^-1) were present throughout. The endothelium was removed by insufflating carbogen through the vessel lumen. Prostaglandin (PG) F_2α, PGE₁ PGE₂, and prostacyclin (PGI₂) elicited concentration-dependent relaxant effects. Removal of the endothelium reduced the relaxation induced by PGE_2α and PGE₂, but not that elicited by PGE₁ and PGI₂. The order of potency was PGE₂? PGE₁? PGI₂? PGF_2α regardless of the presence or absence of endothelium. The relaxation elicited by an acidified solution of NaNO₂ (generating nitric oxide) was almost identical in intact and endothelium-denuded vein segments. The results are compatible with the existence of two prostanoid receptor populations mediating relaxation: (1) one located on the smooth muscle cells and; (2) another present on the endothelium or possibly on the smooth muscle and modulated by the endothelium. The latter receptor appears to be activated by PGF_2α and PGE₂, but not by PGE₁ and PGI₂.     

Stimulation of megakaryocytopoiesis by acute thrombocytopenia in rats

Rats were made acutely thrombocytopenic by injection of antiplatelet serum. Marrow sections and squash preparations were made at intervals during 120 hr. Determinations were made of mitotic index, stage of maturation, ploidy level, and cell size of megakaryocytes; number and size of platelets were measured. Increased endomitosis among megakaryocytes was followed by an increase in the proportion of immature megakaryocytes, a greater average ploidy level of recognized megakaryocytes, and larger megakaryocytes. Maximum changes in these several parameters occurred between 32 and 72 hr after induction of thrombocytopenia. By 120 hr all megakarocyte parameters were near normal. For about 3 days, beginning at about 36 hr, platelet numbers increased rapidly. Average platelet size rose and returned to normal within about 60 hr. Changes in ploidy and size of megakaryocytes were measured in the immature and mature maturation stages. The results suggest that the initial stimulus in response to acute thrombocytopenia acts primarily on diploid precursors, programming them to mature into a population of megakaryocytes with an average ploidy approximately one level greater than in normal rats and a proportionate increase in cell size. The larger megakaryocytes presumably produce more platelets, accounting for a major part of the increased rate of platelet production. Since the changes in megakaryocytes begin to reverse before circulating platelet numbers have reached the normal level, reversal of the stimulus appears to be initiated by some change other than platelet mass.     

Immunoreactive interleukin-6 and acute phase proteins as prognostic factors in multiple myeloma. Finnish Leukemia Group

High serum level of bioactive interleukin-6 (IL-6) is regarded as a predictor of poor prognosis in multiple myeloma (MM). On the other hand, the reported levels of immunoreactive IL-6 have been highly variable, and the prognostic value of immunoreactive IL-6 in MM is not clear. We have analyzed the prognostic significance of serum immunoreactive IL-6, as measured by a sensitive immunosorbent assay, in 210 patients with newly diagnosed MM subsequently treated with intermittent melphalan and prednisone. The serum levels of acute phase proteins C-reactive protein (CRP), alpha 1-antitrypsin (alpha 1AT), and acid alpha 1-glycoprotein (orosomucoid; OM) were evaluated as surrogates for IL-6. Serum IL-6, CRP, alpha 1AT, and OM levels were raised in 42%, 40%, 41%, and 24% of the patients, respectively. There was a significant correlation between the clinical stage of the patients and serum IL-6 (P = .006), alpha 1AT (P = .001), and OM (P = .004) levels at diagnosis. At 3 years, 52% of the patients were alive. Univariate logistic regression analysis showed that high levels of IL-6 (P = .002), CRP (P = .02), alpha 1AT (P < .001), OM (P = .007), beta 2- microglobulin (beta 2M; P < .001), and thymidine kinase (P < .05) were all associated with 3-year mortality. In multivariate regression analysis, beta 2M (P < .0001) and alpha 1AT (P = .01) had independent prognostic significance. The patients with high levels of both beta 2M and alpha 1AT or IL-6 were at very high risk of dying within 3 years from diagnosis (16% and 21% of the patients in these groups were alive, respectively). When the patients were stratified according to the clinical stage, the prognostic significance of serum IL-6 and alpha 1AT was especially evident in stage II patients. When the patients were divided into two groups according to normal or raised serum IL-6 levels, the patients with high IL-6 levels had more frequent osteolytic bone lesions (P = .03) and a more aggressive disease. We conclude that serum immunoreactive IL-6 is a significant prognostic marker in MM.