Acute effects on systemic circulation after intratracheal instillation of Curosurf or Survanta in surfactant-depleted newborn piglets

Systemic vasodilatation in surfactant-depleted newborn piglets is induced by 200 mg/kg of modified porcine lung surfactant (Curosurf™). The aim of this investigation was to study whether this effect is dependent on dose and could further be induced by instillation of a bovine surfactant preparation (Survanta™). Twenty-two 3–5-d old piglets were subjected to repeated saline lung lavage and then randomized to one of three groups. Instillation of either Curosurf 100 mg/kg ( n = 8), Survanta 100 mg/kg ( n = 7) or Curosurf 200 mg/kg ( n = 7) was performed through the endotracheal tube. Systemic vascular resistance decreased 7 (± 4)%, 15 (± 12)% and 18 (± 6)% in the three groups, respectively ( p < 0:05 in all three groups). A significant difference between the high and low dose Curosurf groups was found ( p < 0:05), whereas no significant difference was seen between the Curosurf 100 mg group and the Survanta group. The decrease in vascular resistance was compensated by an increase in cardiac output, resulting in a stable mean arterial blood pressure. In conclusion, both Curosurf and Survanta induce a significant decrease in systemic vascular resistance in surfactant-depleted newborn piglets. A more pronounced effect was observed after 200 mg/kg than after 100 mg/kg of Curosurf.     

Familial hyperproinsulinaemia due to a mutation substituting histidine for arginine at position 65 in proinsulin: identification of the mutation by restriction enzyme mapping

Familial hyperproinsulinaemia is a rare genetic disorder characterized by point mutations in the insulin gene which impair the conversion of proinsulin to insulin. We report here three members of a two-generation Caucasian family in whom this syndrome was identified by unexplained hyperinsulinism associated with normal glucose tolerance and normal insulin sensitivity. Plasma insulin immunoreactivity showed a reduced affinity for the insulin receptor and eluted mainly, on Biogel chromatography, at the position of proinsulin. Analysis of the PCR-amplified insulin gene by restriction enzyme mapping revealed a new recognition site for the enzyme Nla III, indicating a Arg⁶⁵ to His mutation. Sequence analysis of exon 3 confirmed this mutation in one allele of the gene. Conclusion This study reports a two-generation European-Caucasian family with hyperproinsulinaemia due to a substitution of His for Arg at position 65 in proinsulin, the seventh now identified worldwide and the second from Europe. The mutation generated a new restriction site on the insulin gene suggesting the usefulness of restriction enzyme mapping as a screening procedure. Received: 27 June 1997 / Accepted in revised form: 28 November 1997     

A longitudinal,functional study of peripheral nerve recovery in the mouse

Objectives: To verify the validity of the recently described sciatic functional index for mice to monitor neuronal functional recovery over time using a blinded, randomized, and controlled evaluation. Study Design: Surgery was performed on the left sciatic nerves of 62 C57/BL mice after randomly assigning them to one of four surgical groups: sham surgery, sciatic nerve crush, nerve transection without repair, and nerve transection followed by epineurial suture repair. Sciatic functional indices were measured before surgery and then after surgery at 10-day intervals for 90 days, using a previously described formula. Results: Sham surgery did not affect nerve function when compared with preoperative values (P > .24). Crush surgery produced a reversible nerve injury that fully recovered after 20 days. Nerve transection without repair resulted in complete functional disability without recovery of function during the 90-day follow-up interval. When transected nerves were repaired, complete functional disability was noted at day 10, with subsequent functional recovery to 26% of function at day 30. This level of recovery persisted until the 60th postoperative day when muscle contractures resulted in progressive worsening of the index. There were statistically significant differences between the sciatic functional indices of each of the groups (P < .05). Conclusions: The previously described sciatic functional index for mice is an accurate indicator of the level of sciatic neuronal function during recovery. This index represents a method of evaluating neuronal function that may provide a better reflection of the recovery parameters that are important in clinical situations. The sciatic functional index will allow for study of sciatic nerve functional recovery in genetically engineered transgenic mice.     

No evidence of significant activity of the multidrug resistance gene product in primary human breast cancer

Background: The discovery of the multidrug resistance (MDR1) gene product P-glycoprotein (P-gp) has been widely seen as an important milestone in our understanding of the mechanisms underlying the clinical phenomenon of the emergence of resistant cells. MDR1 expression has been shown for numerous solid tumors and for virtually all hematologic malignancies. Nevertheless, results regarding MDR1/P-gp expression in human breast cancer have been controversial and the results of clinical trials on modulation of P-gp activity have not been encouraging.Patients and methods: MDR1/P-gp expression and the function of the P-gp pump were investigated in 61 tumor samples from patients with primary breast cancers by multiparameter analysis using MDR1-RT-PCR, immunohistochemistry with two MAbs (UIC2 and MRK 16) and the rhodamine 123 (Rh123) efflux assay. The cellular composition of the tumor cell suspension was analyzed by using specific MAbs against the P-gp expressing lymphocyte subsets CD4, CD8 and CD56, as well as against the HER-2/neu gene product, which was used to identify breast carcinoma cells.Results: UIC2 and MRK16 revealed a staining positivity in 72% and 75% of samples, respectively. A positive MDR1-RT-PCR signal was detected in 62% of the samples. Nevertheless, no correlation between immunohistochemistry and RT-PCR could be established. Furthermore, there was no correlation between HER-2/neu expression and MDR1-RT-PCR or P-gp immunohistochemical assays. A contamination by CD8+ and CD4+ lymphocytes was established in 100% and 84% of tumor cell suspensions, respectively. As assessed by the Rh123 efflux assay CD8+ and the CD4+ lymphocytes exhibited marked P-glycoprotein activity, whereas such activity was not detectable in a single instance for the breast carcinoma cells. In MDR1-RT-PCR positive samples, contamination by CD8 lymphocytes averaged 4.3%, while the contamination of CD8 cells in the MDR1 mRNA-negative samples was only 2.4% (P = 0.007). This signal vanished after elimination of the lymphocyte subpopulations by T-cell rosetting.Conclusions: In primary breast cancer detection of MDR1 gene expression by means of RT-PCR or immunohistochemical assays is not indicative for the MDR phenotype, since there is no evidence of significant activity of the P-gp pump.     

ESTABLISHMENT OF CRITERIA FOR MEASURING MDR-1 GENE EXPRESSION LEVEL IN BREAST CANCER BY RT-PCR

ＥＳＴＡＢＬＩＳＨＭＥＮＴＯＦＣＲＩＴＥＲＩＡＦＯＲＭＥＡＳＵＲＩＮＧＭＤＲ１ＧＥＮＥＥＸＰＲＥＳＳＩＯＮＬＥＶＥＬＩＮＢＲＥＡＳＴＣＡＮＣＥＲＢＹＲＴＰＣＲＬｉｕＸｉａｏｑｉｎｇ刘晓晴ＳｏｎｇＳａｎｔａｉ宋三泰ＳｈｉＣｈｅｎｇｈｕａ石成华ＸｕＪ...     

急性早幼粒细胞白血病多药耐药基因mdrl的表达及其临床意义

为探讨急性早幼粒细胞白血病多药耐药基因mdrl与患者化疗疗效的关系利用反转录─聚合酶链反应（RT－PCR）方法，检测了31例APL患者mdrlmRNA的表达，同时检测了急性髓细胞白血病（AML）其他亚型37例及正常人20例。结果发现APL患者mdrl的阳性率，明显低于其他亚型（P＜0．005），APL患者mdrlmRNA的表达水平（0．218±0．07）也低于其他亚型（0．556±0．25）（P＜0．001）。12例初治APL患者mdrl全部阴性，完全缓解（CR）率为100％，4例复发ALP患者中3例mdrl阳性（75％）。在AML其他亚型，mdrl+与mdrlt-的CR1率分别为33．3％（3／9）和81．8％（9／11）。结果表明，mdrl的表达与患者化疗效果及预后密切相关，APL患者的mdrl为低表这。     

正常卵巢与多囊卵巢的颗粒细胞E_2和P的产生及其卵泡液中E_2和雄烯二酮(A)含量的比较

为了解正常卵巢与多囊卵巢(PCO)颗粒细胞功能的异同.本研究对12例正常人卵泡期的25个卵泡和7例PCO的约60个卵泡的颗粒细胞进行了培养,用放免法测定卵泡液中雌二醇(E_2)和雄烯二酮(A)及培养液中E_2和孕酮(P)的含量.结果表明PCO的颗粒细胞对FSH和LH刺激更敏感,产生更多的E_2和P.FSH(10ng/ml)作用下PCO组产生的E_2和P分别比正常组高8.8倍(P<0.001)和2.6倍(P<0.05).LH(10ng/ml)作用下PCO组产生的E_2和P也分别高4.8倍(P<0.01)和2.0倍(P>0.05);PCO卵泡液中A的含量明显高于正常对照(P<0.05).PCO的颗粒细胞甾体激素合成酶的活性增高,可能是PCOS病人的高LH和高INS血症起关键作用.     

针刺影响下丘脑性肥胖大鼠脂代谢相关因素的分析

目的:通过针刺肥胖大鼠并作相关实验分析,探讨针刺减肥效应的某些机理。方法:将实验大鼠分为正常组、模型组、针刺组、西布曲明组,观察各组大鼠体重指数(Lee’s指数)、左肾周脂肪重量和脂肪细胞体积、脂质代谢、胰岛素、瘦素及神经肽Y的变化,分析其相互作用与联系。结果:针刺组与模型组相比体重指数、脂质代谢有明显改善(P<0.01),左肾周脂肪湿重降低,脂肪细胞体积减小,与西布曲明组比较针刺组作用更好(P<0.05);针刺组与模型组比较血清胰岛素、瘦素水平明显降低(P<0.01),西布曲明组与模型组比较血清胰岛素、瘦素水平也趋降低(P<0.05);针刺组与模型组比较瘦素与神经肽Y之间有协调趋向,但分布并不一致,西布曲明组则无明显变化。结论:针刺具有减小体重指数、改变脂肪细胞体积、调节脂代谢功能的作用,且可能通过协调机体胰岛素、瘦素及神经肽Y分泌水平而达到降脂减肥目的。