Tumor cell-enhanced sensitivity of vascular endothelial cells to photodynamic therapy

Effective antitumor photodynamic therapy (PDT) may be related to damage of vasculature within the tumor. The purpose of this study was to determine if tumor cells secrete factors that stimulate proliferation of human umbilical vein endothelial cells (HUVEC) and result in enhanced sensitivity of HUVEC to aluminum-sulfonated phthalocyanine (AISPc)-PDT. Three human tumor cell lines—pharyngeal squamous carcinoma, colonic carcinoma, and mammary carcinoma—were used in this study. Co-culture of HUVEC and either squamous carcinoma or colonic carcinoma, but not mammary carcinoma, significantly increased HUVEC proliferation and AlSPc-PDT mediated cell damage. In addition, supernatant from squamous carcinoma and colonic carcinoma cultures also stimulated HUVEC proliferation and sensitivity to AISPc-PDT. Both supernatant and cell lysate from squamous carcinoma cells contained angiogenic factors consistent with basic and acidic fibroblast growth factors, as evidenced by Western blot analysis and BALB/c 3T3 fibroblast cell proliferation assays. Collectively, these results suggest that selected tumor cell lines produce angiogenic factors that induce HUVEC proliferation and subsequently enhance sensitivity to AISPc-PDT. © 1994 Wiley-Liss, Inc.     

缺血性脑血管病与颈动脉粥样硬化及其危险因素的关系

目的探讨缺血性脑血管病(ICVD)与颈动脉粥样硬化及其危险因素的关系。方法对186例ICVD患者与194例非脑血管病患者和正常体检者(对照组)行颈部血管超声检查和血液生化检查;比较两组间的颈动脉硬化程度及脑卒中危险因素的差异。结果ICVD组年龄[(69±7)岁]和患有高血压(66.1%)、糖尿病(53.4%)、代谢综合征患者(44.6%)的比率非常明显高于对照组[(61±5)岁、48.8%、15.2%、12.9%](均P<0.001)。ICVD组颈动脉粥样硬化分级计分≥2分(斑块发生率)、≥3分(血管狭窄发生率)分别为69.3%、20.4%,明显高于对照组的33.5%和5.1%(均P<0.05)。结论颈动脉粥样硬化是ICVD的危险因素之一;各种危险因素的聚集对ICVD的发生起重要作用。     

Activation of guinea pig eosinophil respiratory burst by leukotriene B4: role of protein kinase C

Leukotriene B4 (LTB4) and the protein kinase C activator, 4-beta-phorbol dibutyrate (PDBu), both induced a pronounced and concentration-dependent stimulation of hydrogen peroxide (H2O2) generation by purified guinea pig peritoneal eosinophils in the concentration range 1 nM-1 microM. The LTB4 response was inhibited competitively by the specific LTB4 receptor antagonist, U-75302, with a KB of 25 nM, while the concentration-response curves for both stimuli were shifted rightwards (3.8-fold and 2.8-fold for LTB4 and PDBu, respectively) by the competitive protein kinase C inhibitor, 1-O-hexadecyl-2-O-methylglycerol at a concentration of 300 microM. LTB4 appears, therefore, to induce respiratory burst in eosinophils via a receptor-mediated mechanism involving protein kinase C.     

Cerebrospinal fluid-filtration reduces TNF alpha in bacterial meningitis-CSF

A 37 year old male was admitted with the diagnosis of bacterial meningitis. Pneumococci were seen in the Gram stain of the cerebrospinal fluid. The clinical condition did not suggest severely raised intracranial pressure, there were no localizing signs and symptoms. CSF was turpid, with 20.100/3/mm³, mainly polymorphonuclear cells. Tumor necrosis factor alpha in CSp was greatly increased with 813 pg/ml. Parallel to the application of intravenous Penicillin G a CSF filtration was carried out. Within 214 h 225 ml CSF were filtrated through a Pall-filter, using a bidirectional pump. Cell count dropped to 720/3 cells/mm³, TNF-alpha to 39 pg/ml. The clinical course was uneventful, on day 12 the patient could be discharged without sequelae. CSF filtration may be a highly effective method to reduce from the CSF pathogenetically important cytokines, such as TNF-alpha, being responsible for intrathecal/meningeal inflammatory processes and triggered by cell-wall components of bacteria, e.g. pneumococci.     

In vitro radiation sensitivity of the lncap prostatic tumor cell line

Because there is extremely limited information on the intrinsic radiosensitivity of human prostatic cancer cells, we have investigated the in vitro radiation response of exponentially growing LNCaP cells. Due to the very poor colony-forming potential of the LNCaP cells, radiation survival was investigated using the dose-dependent (0-6 Gy) changes seen after X-irradiation in the shapes of regrowth curves. Survival was described using both the single-hit, multitarget (SHMT) equation and the linear-quadratic (LQ) equation. The values and 95% confidence limits of the extrapolation number (n), quasi-threshold dose (D_q), and mean lethal dose (D_o) in SHMT terminology were respectively: 0.9 (0.7-1.0), 0.0 Gy, and 1.39 (0.11) Gy. The LQ alpha and beta parameters were respectively 6.80 (1.13) and -0.53 (2.89). The X-ray dose response of the LNCaP line is, therefore, purely exponential. The mean survival at the clinically relevant dose of 2 Gy (S₂) was 51.2% for the LNCaP line. Comparison of the S₂ value for the LNCaP line with previous investigations with other human prostatic cancer cell lines (DU145 and PC-3) indicates a mean S₂ value of 47.6%, which suggests that human prostate cancer cells might lie toward the resistant side of the spectrum for various classes of human neoplasms. © 1994 Wiey-Liss, Inc.     

Dyskeratosis congenita: Unusual onset with isolated neutropenia at an early age

A 3.5 year old male patient with dyskeratosis congenita (DC) presented at the age of 13 months with isolated neutropenia preceding characteristic skin findings. The average absolute neutrophil count of 500/mm³ persisted without the presence of anemia or thrombocytopenia during the follow up. Neutropenia responded to granulocyte-colony stimulating factor (G-CSF) at a dose of 10 μg/kg per day. Immunologic findings were normal as was the chromosomal stability and sister chromatid exchange.     

停跳或不停跳心脏手术对血清 S-100B蛋白表达的影响

【目的】研究心脏手术围术期血清S-100B蛋白表达及其与停跳或不停跳心肺转流方式和时间的关系。【方法】体外循环心脏手术患者23例,测转流前、转流10min、转流末、转流后24h的血清S-100B蛋白表达水平。【结果】①血清S-100B蛋白质量浓度在体外循环前后动态变化:转流前(M)为0.27μg/L,转流10min后升至0.57μg/L(P<0.01),转流末达峰值1.80μg/L(P<0.01),转流后24h降为0.22μg/L(P>0.05)。转流末的血清S-100B蛋白质量浓度与转流时间呈正相关(r=0.488,P<0.05)。②停跳组(n=6)转流前、转流10min、转流末、转流后24h平均血清S-100B蛋白质量浓度分别为(0.17±0.09)μg/L、(0.48±0.13)μg/L、(1.65±0.52)μg/L和(0.19±0.04)μg/L,不停跳组(n=6)分别为(0.26±0.14)μg/L、(0.71±0.41)μg/L、(1.59±0.84)μg/L和(0.23±0.11)μg/L,两组差别无统计学意义(P>0.05)。【结论】体外循环可导致血清S-100B蛋白表达增高,其表达水平与心肺转流时间呈正相关,但与停跳或不停跳转流方式无关。     

再生障碍性贫血患者血清一氧化氮与细胞因子水平分析

生物体内的一氧化氮 (NO)作为一种反应极强的效应分子 ,不仅参与免疫调控 ,而且也是造血祖细胞生长和分化不可缺少的调节因子 [1 ]。本文通过对再生障碍性贫血 (AA)患者血清 NO与白细胞介素 - 2 (IL- 2 )、肿瘤坏死子 (TNF)、血小板生成素 (TPO)、红细胞生成素 (EPO)、GM- CSF、5种细胞因子水平测定 ,分析其与外周血象及各细胞因子间的相互关系 ,并探讨 NO及 IL- 2等细胞因子在 AA发生发展过程中的作用。1　材料和方法1.1　材料1.1.1　标本来源　 AA患者 5 0例 ,以 2 0 0 2年 3月至 2 0 0 4年4月我院确诊为 AA的患者为研究对象…     

Editorial

Aim: Wall stress‐independent signalling pathways were studied for endothelin‐1 (ET‐1)‐induced c‐fos expression in rat intact mesenteric small arteries. Methods: Arteries were kept unmounted in Krebs buffer, equilibrated for 1 h and stimulated with vasoactive substances for 15–60 min. The c‐fos mRNA expression was determined by real‐time polymerase chain reaction. Results: Stimulation with fetal bovine serum (FBS), phorbol 12‐myristate 13‐acetate (PMA) and ET‐1 caused about a doubling of c‐fos mRNA. The ET‐1‐induced c‐fos expression was steady (15–60 min) and was inhibited by the inhibitor of the ET_A receptor, BQ‐123. Platelet‐derived growth factor‐B, angiotensin II and U46619 did not cause increased c‐fos mRNA levels. The broad specificity inhibitor staurosporine inhibited the response to ET‐1, but inhibitors of Rho‐A kinase and phosphatidylinositol 3‐kinase had no effect. However, inhibitors to tyrosine kinases, the MAP kinases [extracellular signal‐regulated kinase 1/2 (ERK1/2), c‐Jun amino‐terminal kinase, p38], and to conventional protein kinase C showed no inhibition. Consistent with these findings, ET‐1 did not cause activation of ERK1/2, a finding also seen in vessels held under pressure. In contrast, ET‐1‐induced c‐fos expression was inhibited by the calcium chelator BAPTA, suggesting a role for intracellular calcium. This possibility was supported by the finding that raising the extracellular K⁺ concentration caused increased expression of c‐fos in a concentration‐dependent manner. Conclusion: The results suggest that in the absence of wall stress, ET‐1 is able to induce increased expression of c‐fos independent of traditional growth pathways, such as MAP kinase. The mechanism appears to be calcium‐dependent.