Interleukin-1 alpha gene-transcription in murine keratinocytes is inhibited by HSV-1 infection

The effect of in vitro infection with herpes simplex virus 1 (HSV-1) on the Interleukin-1 (IL-1) activity of murine keratinocytes was investigated. IL-1 alpha mRNA synthesis was measured by the Northern blot technique, and the IL-1 protein production was measured in terms of the ability of dialysed supernatants from cultures of uninfected and HSV-1 infected keratinocytes to enhance mitogen-induced murine thymocyte proliferation. IL-1 alpha mRNA-synthesis in uninfected keratinocytes was detected 24 h and 48 h after isolation of the keratinocytes. IL-1 protein secretion by these keratinocytes was measureable at 18 h and reached a peak of 73 h, whereas intracellular and membrane-bound IL-1 protein production reached a maximum after 25 h. Keratinocytes, which had been cultured in vitro for 18 h, were infected with HSV-1 for 2 h and further cultured for an additional 4 h or 22 h before IL-1 measurements. A marked reduction of IL-1 alpha gene-expression was noted 6 hours after HSV-1-infection of keratinocytes, and nearly total shut-off was detected after infection for 24 h. Reduced gene-expression was paralleled by a reduction in the IL-1 protein secretion from the HSV-1 infected keratinocytes.     

高效液相色谱法测定右旋儿茶素血浆浓度及药代动力学参数

本文建立了体液中右旋儿茶素的RP-HPLC测定方法。采用C_(18)键合相硅胶为填料的固相提取柱进行样品预处理,右旋儿茶素的提取回收率为79.8%.应用二极管阵列检测器对色谱峰纯度进行鉴定。该法精密度好,方法回收率近100%,日内、日间的变异系数为2.4～5.6%,血浓69.6～1160 ng/ml范围内呈线性关系,r=0.9993。家兔静注右旋儿茶素18mg/kg,其药代动力学过程符合二室模型,分布相半衰期为0.129 h,消除相半衰期为1.19h。     

Role of Langerhans cells and Thy. 1+ effector cells in herpes simplex virus-1 infection in the skin of newborn mice

Summary Langerhans cells function in the epidermis as very potent accessory cells. Their role as antigen-presenting cells in the immune response following herpes simplex virus type 1 (HSV-1) skin infection of newborn mice was studied. Newborn C 57 BL/6 mice were found to be susceptible while adult mice are resistant to HSV-1 infection in the skin. Because the immune response to HSV-1 infection in the skin is mainly cell-mediated, and therefore dependent on the presence of functional accessory cells, the state of Langerhans cells in the skin of newborns was studied. Staining of whole epidermal mounts revealed similar numbers of Ia⁺ and ATPase⁺ Langerhans cells in the epidermis of newborn and adult mice. In a skin lymphocyte reaction assay, Langerhans cells derived from newborn mice were shown to stimulate proliferation of T cells derived from adult allogeneic mice to the same degree as adult-derived Langerhans cells. HSV-1 was injected into the skin of C 57 BL/6 newborn mice together with various preparations of adult-derived spleen cells devoid of antigen-presenting cells. The injected adult-derived lymphocytes were found to confer protection against HSV-1 infection in newborn mice, despite the lack of detectable antigen-presenting cell (APC) function in this cell preparation. The cell subset involved in the transfer of resistance was found to be Ia^– and Thy. 1⁺.     

Radiologically placed temporary hepatic artery catheter for treatment of liver cancer

Hepatic artery infusion (HAI) chemotherapy is associated with higher response rates compared to systemic chemotherapy in those patients with unresectable liver malignancies. Operative hepatic artery catheter (HAC) insertion has significant morbidity and mortality, especially in patients with high‐volume disease, some of whom may not respond to HAI chemotherapy. We report our experience in 45 patients with high‐volume liver disease who were initially treated with HAI chemotherapy via a radiologically placed temporary HAC to try to select the responders who then went on to have an operative HAC. In these 45 patients who had 62 radiologically placed HAC, we found very few major complications, and certainly no complications such as cholecystitis, vascular or malperfusion problems.     

Procoagulant activity of reversibly acylated human factor Xa

The plasma clotting factors used to treat hemophiliacs who have developed inhibitory antibodies have a shared history of limited clinical safety and utility. To improve on existing bypass factors, we have developed a reversibly acylated form of human plasma factor Xa capable of providing a time-dependent release of procoagulant activity. Factor Xa was treated with p-amidinophenyl p'-anisate to generate anisoyl Xa. The chemical modification of the protein involves acylation of the active site serine residue of factor Xa. Anisoyl Xa deacylated in a time, pH, and temperature-dependent manner. Active factor Xa generated on deacylation of anisoyl Xa exhibited amidolytic and prothrombinase complex activities in in vitro assays, the level being comparable to those of untreated factor Xa. When Anisoyl Xa was infused into rabbits, active factor Xa was generated on deacylation of the acylated enzyme, which shortened the activated partial thromboplastin time (APTT) in a dose-dependent manner. The duration of effect on rabbit APTT could be directly correlated to the level of human plasma factor Xa. Because anisoyl Xa bypasses the "tenase" complex that is compromised in hemophilia A and B and is unaffected by inhibitory antibodies, it has the potential to be used as an effective bypass therapy.     

Effects of combination cholestyramine-neomycin treatment on plasma lipoprotein concentrations in type II hyperlipoproteinemia

Recent prospective clinical trials have established that cholesterol reduction in patients with elevated (upper 90th percentile) concentrations of low-density lipoproteins (LDL) reduces the incidence of myocardial infarction and sudden death. Because the level of protection from these cardiovascular sequelae is directly related to the degree of LDL reduction, combination therapy using different hypolipidemic agents has been used in patients with type II hyperlipoproteinemia (HLP). Neomycin is as effective as cholestyramine in reducing LDL levels and combination neomycin-niacin treatment normalizes the plasma lipoproteins in 92% of patients with type II HLP. Because neomycin could theoretically ameliorate some of the gastrointestinal side effects of cholestyramine in addition to further affecting cholesterol levels, the effects of combination cholestyramine-neomycin treatment on the plasma lipoprotein were assessed in 18 patients with type II HLP in a 9-month clinical trial. Compared with diet-only treatment, cholestyramine reduced total and LDL cholesterol levels by 77 mg/dl (22%) and 78 mg/dl (31%), respectively. In addition to relieving cholestyramine-induced constipation, neomycin further reduced the total cholesterol level by 20 mg/dl (6%). However, this further reduction in total cholesterol concentration was the result of a decrease in the concentration of high-density lipoprotein cholesterol. These findings indicate that combination therapy does not have an additive LDL cholesterol-lowering effect and that neomycin and cholestyramine is not a useful drug combination. In addition, these results illustrate the importance of determining the high-density lipoprotein cholesterol concentration to fully interpret the effects of hypolipidemic treatment.