No abstract

The response of cells of the murine megakaryocytic lineage to human interleukin 6 (IL-6) was asse in serum-depleted cultures using a variety of biological assays.IL-6 alone had no influence on megakaryocytic colony formation but augmented the numbers of these colonies induced by the multipotent colony-stimulating factor interleukin 3. However, in liquid marrow cultures, IL-6 alone promoted marked increments in megakaryocytic size and the activity of acetylcholinesterase, a marker enzyme ofthe lineage. Moreover, IL-6 induced a signicant shift toward higher ploidy classes when megakaryocytic DNA was quantitated by flow cytometry. To determine whether the influence of IL-6 on megakaryocytic maturation was direct, the factor was added to cultures of single megakaryocytes isolated from megakaryocytic colonies.Fifty-four percent ofthese cells increased in size compared with 19% of those grown without HL-6. The data show that human IL-6 is a potent direct-acting growth factor for murine megakaryocytes with activity promoting maturation of that lineage.Megakaryocytopoiesis is a process that encompasses proliferation of committed megakaryocytic progenitor cells (CFU-MK) and cellular maturation comprising nuclear endoreduplication (polyploidization), cytoplasmic enlargement, and accumulation of lineage markers (1-3). This process appears, at least in vitro, to be stimulated by a number of cytokines. The multipotent colony-stimulating factor interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin have been shown to promote the proliferation of megakaryocytic progenitors (4-6). Moreover, these growth factors can support not only proliferation, but also megakaryocytic maturation to some degree (7-9). These observations, nonetheless, do not exclude the idea that there exist growth factors that act predominantly to influence either proliferation or maturation. In this report the effects of recombinant human interleukin 6 (IL-6) on murine megakaryocytopoiesis are described. This 26,000 Mr glycoprotein with multiple biological activities has been purified to homogeneity from both murine and human sources and recently has been molecularly cloned (10-12). We now show that this cytokine significantly augments megakaryocytic maturation as assessed by size, acetylcholinesterase (AcChoEase) activity, and DNA content and that it synergizes with the megakaryocyte-growth-promoting activity of IL-3. MATERIALS AND METHODSMarrow Preparation. Marrow was flushed from the femurs of C57BL/6 mice with Iscove's modification of Dulbecco's medium (IMDM) supplemented with Nutridoma-SP (Boehringer Mannheim), a serum-free medium supplement. For culture studies, a single-cell suspension was made by repetitive expulsion through progressively smaller needles. For flow cytometry, a monocellular suspension was made by gentle filtration through 100-,um nylon mesh. In some experiments marrow cells were treated with 0.5 mM diisopropylfluorophosphate to inactivate endogenous AcChoEase (a marker enzyme of mega...

The ELAPSS score consists of 6 easily retrievable predictors and can help physicians in decision making on the need for and timing of follow-up imaging in patients with unruptured intracranial aneurysms.

The present study provides evidence that the LOX-1-MT1-MMP axis plays a crucial role in RhoA and Rac1 activation signalling pathways in ox-LDL stimulation, suggesting that this axis may be a promising target for treating endothelial dysfunction.

Background and Purpose-The natural history of unruptured intracranial aneurysms remains unclear, and management strategy is not well defined. Methods-From January 2003 to December 2012, we enrolled patients with aneurysm in our institution. In total, 2252 patients with 2897 aneurysms were eligible for analysis, and 1960 eligible aneurysms were conservatively managed. Precise 3-dimensional evaluation was conducted using computed tomography angiography, digital subtraction angiography, or magnetic resonance angiography. We then assessed the risk of aneurysm rupture, mortality, and morbidity associated with aneurysm characteristics, demographics, and known health/lifestyle risk factors. Results-The mean follow-up duration was 7388 aneurysm-years. During observation, 56 aneurysms ruptured, resulting in an overall rupture rate per year of 0.76% (95% confidence interval, 0.58-0.98). The mean initial visit to rupture interval was 547 days. Aneurysm size, location, daughter sac, and history of subarachnoid hemorrhage were significant independent predictors for aneurysm rupture. Aneurysms that were ≥5 mm were associated with a significantly increased risk of rupture when compared with 2-to 4-mm aneurysms (unadjusted hazard ratio, 12.24; 95% confidence interval, 7.15-20.93). Of 56 patients who experienced hemorrhage, 29 (52 %) died or were rendered severely disabled. Of the patients who had large or giant aneurysms, none recovered without deficits, and the mortality rate after rupture was 69%. For aneurysms sized <5 mm, the mortality rate was 18%. Conclusions-Larger

Backgrounds and Purpose-The authors evaluated the incidence of rupture of unruptured intracranial saccular aneurysm during observation. Methods-Between January 2003 and December 2006, a total of 419 patients with 529 unruptured intracranial saccular aneurysms were observed without treatment. The mean follow-up duration was 905.3 days. Aneurysm size was measured by 3-dimensional CT angiography. Clinical and 3-dimensional CT angiography follow-up were obtained every 6 months. Results-Nineteen aneurysms ruptured during observation resulting in a 1.4% rupture rate per year. A history of subarachnoid hemorrhage (hazard ratio, 7.3; 95% CI, 2.5 to 21.2), posterior circulation aneurysm (hazard ratio, 2.9; 95% CI, 1.1 to 8), and large size were significant independent predictors for aneurysm rupture. Conclusions Clinical Materials and MethodsFrom January 2003 through December 2006, a total of 419 patients with 529 UIAs were referred to our institution. Patient information and clinical presentation is summarized in Table 1.Size of the UIAs was measured by 3-dimensional CT angiography (Sensation16, Siemens, Germany). Based on the findings of 3-dimensional CT angiography, all UIAs were classified into the following categories: small (S; 0 to 4.9 mm in diameter), medium/ small (MS; 5 to 9.9 mm in diameter with small neck (0 to 3.9 mm), medium/wide (MW; 5 to 9.9 mm in diameter) with a wide neck (Ͼ4 mm), large (L; Ͼ10 mm), and giant (G; Ͼ25 mm). These aneurysms were followed by 3-dimensional CT angiography every 6 months.Data were analyzed using the biomedical data package statistical program (Version 7.0; BMDP Statistical Software, Inc, University of California, Los Angeles, Calif). Categorical variables were compared using the Fisher exact 2-tailed test, the Pearson 2 test, or the test for determining linear trend. Continuous variables were compared among groups by using the Mann-Whitney U test or the Student t test. For life-table analysis and Cox proportional hazards regression model, each patient was followed to the time of subarachnoid hemorrhage (SAH), death due to causes other than SAH, or to the last possible follow-up contact. The average annual incidence of SAH was calculated by determining the number of first-event SAH divided by the number of person-years of follow-up. Cumulative rates of SAH were estimated using the Kaplan-Meier product-limit method. ResultsNineteen aneurysms ruptured during the follow-up period. The annual incidence of SAH was 1.4% during observation. Incidence of rupture was strongly correlated with aneurysm size. The annual rupture rate by size classification was 0.8% (S), 1.2% (M), 7.1% (L), and 43.1% (G), respectively. Details of ruptured aneurysms under conservative observation are summarized in Table 2.In patients with a history of SAH, the hazard ratio (HR) was 7.3 (95% CI, 2.5 to 21.2, PϽ0.001). Particularly in S-sized UIAs, 2 of 8 (25%) were associated with a history of SAH. The risk of rupture in S-sized UIAs with a history of SAH was 5.5 (95% CI, 0.9 to 32.4) compared with patients ...

We conclude that low-frequency ultrasound transmits well through human temporal bone and enhances thrombolysis in vitro. Clinically, this method may be promising for reducing dosages of thrombolytic agents and shortening the period of clot removal.

Background-Lysophosphatidylcholine] i increase caused by LPC. This suppressive effect was quickly reversed by geranylgeranylpyrophosphate (GGPP) and was mimicked by inhibitors of Rho and Rho kinase. LPC induced the translocation of the GTP-bound active form of RhoA into membranes within 1 minute as determined by a pull-down assay and reduced the levels of RhoA in the cytoplasm, indicating that LPC quickly increases the GTP/GDP ratio of RhoA and induces membrane translocation. Statins prevented the GTP/GDP exchange of RhoA and its membrane translocation from the cytoplasm caused by LPC, and these effects of statins were reversed by GGPP. The responses of RhoA activation to statins and GGPP concurred with their effects on Ca 2ϩ mobilization. LPC also induced a nonselective cation current after a lag. Statins prolonged the lag and decreased the current amplitude, and GGPP abolished the inhibitory effect on the current. Conclusions-LPC induced