巨噬细胞集落刺激因子对小鼠腹腔巨噬细胞清道夫受体途径和细胞内胆固醇酯积聚的影响

为探索巨噬细胞集落刺激因子、清道夫受体、氧化型低密度脂蛋白与动脉粥样硬化的关系，观察了重组人巨噬细胞集落刺激因子对小鼠腹腔巨噬细胞清道夫受体途径的影响以及重组人巨噬细胞集落刺激因子对氧化型低密度脂蛋白所致细胞内胆固醇酯积聚的影响．结果发现重组人巨噬细胞集落刺激因子能增加培养的小鼠腹腔巨噬细胞表面的清道夫受体数目，使之对氧化型低密度脂蛋白的结合和降解呈现剂量和时间依赖性增加，并使细胞内胆固醇酯积聚增多．表明巨噬细胞集落刺激因子可通过增加清道夫受体数目使小鼠腹腔巨噬细胞对氧化型低密度脂蛋白的结合和降解增多，从而增加细胞内胆固醇酯含量，促进动脉壁内泡沫细胞形成．     

蛋白激酶C抑制剂对宫颈癌细胞化疗药物耐药的影响

目的观察蛋白激酶C抑制剂星形孢菌素对经紫杉醇处理的宫颈癌细胞增殖、凋亡及蛋白激酶C、P-糖蛋白（P-gp）表达的变化,探讨蛋白激酶C抑制剂对宫颈癌细胞紫杉醇耐药的影响。方法培养人宫颈癌Hela细胞,设立星形孢菌素组、紫杉醇组、联合组及对照组。星形孢菌素组加入星形孢菌素0.6μmol/L;紫杉醇组加入紫杉醇0.1μmol/L;联合组先加入星形孢菌素0.6μmol/L,随后加入紫杉醇0.1μmol/L;对照组不加入星形孢菌素及紫杉醇。四组细胞干预后继续培养48 h,采用MTT法检测细胞增殖能力,流式细胞术检测细胞凋亡率,Western blot法检测蛋白激酶C及P-gp蛋白表达。结果星形孢菌素组、紫杉醇组及联合组增殖抑制率分别为38.11%±0.70%、49.96%±1.60%及60.31%±1.80%,联合组增殖抑制率高于星形孢菌素组及紫杉醇组（P均〈0.05）,星形孢菌素组增殖抑制率低于紫杉醇组（P〈0.05）。对照组、星形孢菌素组、紫杉醇组及联合组细胞凋亡率分别为7.13%±0.56%、17.73%±0.59%、36.51%±0.34%、56.72%±0.68%,星形孢菌素组、紫杉醇组及联合组细胞凋亡率均高于对照组（P均〈0.05）,联合组细胞凋亡率高于其他三组（P均〈0.05）。星形孢菌素组、联合组蛋白激酶C及P-gp蛋白表达均低于对照组（P均〈0.05）,联合组蛋白激酶C及P-gp蛋白表达均低于星形孢菌素组、紫杉醇组（P均〈0.01）。结论星形孢菌素可抑制经紫杉醇处理后的宫颈癌细胞的增殖、促进其凋亡,改善宫颈癌细胞对紫杉醇的耐药性。星形孢菌素可能通过减少P-gp蛋白表达改善宫颈癌细胞对紫杉醇的耐药性。     

A类清道夫受体N端第1～27位氨基酸胞浆结构域缺失对功能的影响

目的确定A类清道夫受体胞浆域中的信号序列，探讨其对于受体功能的影响。方法构建A类清道夫受体N端第1～27位氨基酸胞浆结构域缺失体的表达质粒，并将其经脂质体介导瞬时转染入CHO细胞中。用Western blot检测A类清道夫受体在细胞中的表达，并用流式细胞仪定量检测转染后的蛋白表达效率。用DiI标记的乙酰化低密度脂蛋白与转染的细胞共孵育，激光共聚焦显微镜下观察乙酰化低密度脂蛋白在细胞内的分布，并进行荧光定量分析。结果A类清道夫受体N端第1～27位氨基酸胞浆结构域缺失体可大量表达于转染细胞膜和细胞浆。在高浓度乙酰化低密度脂蛋白刺激下，A类清道夫受体N端第1～27位氨基酸胞浆结构域缺失体的细胞内定位发生变化，也可存在于转染细胞核内。A类清道夫受体N端第1～27位氨基酸胞浆结构域缺失体摄取DiI标记乙酰化低密度脂蛋白的能力较全长相比下降约60％，细胞粘附能力较全长A类清道夫受体相比则下降约8．9％。结论A类清道夫受体的N端第1～27位氨基酸结构对于A类清道夫受体在细胞内的定位表达、结合和摄取配体以及调节细胞粘附的功能具有重要的作用。     

两种细胞因子和表皮生长因子、纤维母细胞生长因子对血管平滑肌细胞清道夫受体活性的影响

为探讨有关的细胞因子和生长因子是否影响平滑肌细胞清道夫受体与氧化型低密度脂蛋白结合活性，以Ｃｕ２＋氧化法制备的氧化型低密度脂蛋白免疫豚鼠，制备抗氧化型低密度脂蛋白抗体，在培养的小牛主　动脉平滑肌细胞中，用细胞酶联免疫吸附检测法测定清道夫受体结合氧化型低密度脂蛋白的活性。结果发现，碱性纤维母细胞生长因子、表皮生长因子、肿瘤坏死因子可提高血管平滑肌细胞表面清道夫受体活性，而粒细胞－巨噬细胞集落刺激因子对清道夫受体活性无影响。此结果提示，某些细胞因子、生长因子对平滑肌细胞清道夫受体活性具有调节作用。     

两种细胞因子和表皮生长因子、纤维母细胞生长因子对血管平滑肌细胞清道夫受体活性的影响

为探讨有关的细胞因子和生长因子是否影响平滑肌细胞清道夫受体与氧化型低密度脂蛋白结合活性，以Ｃｕ＾２＋氧化法制备的氧化型低密度脂蛋白免疫豚鼠，制备抗氧化型低密度脂慢白抗体，在培养的小牛主动脉平滑肌细胞中，用细胞酶联免疫吸附检测法测定清道夫受体结合氧化型低密度脂蛋白的活性。结果发现，碱性纤维母细胞生长因子、表皮生长因子、肿瘤坏死因子可提高血管平滑肌细胞表面清道夫受体活性，而粒细胞－巨噬细胞集落刺激因子     

硫酸乙酰肝素蛋白聚糖及肝素对巨噬细胞脂质蓄积的抑制作用

用苏丹Ⅳ染色观察巨噬细胞内脂质聚积的变化；通过酶－荧光法检测巨噬细胞内胆固醇含量并检测125Ⅰ标记氧化型低密度脂蛋白降解量来反映巨噬细胞清道夫受体的活性，以探讨硫酸乙酸肝素蛋白聚糖及肝素对巨噬细胞脂质蓄积的影响及机制。结果发现，氧化型低密度脂蛋白（100mg／L）组巨噬细胞的胞浆内可见较多苏丹Ⅳ着色红染颗粒，氧化型低密度脂蛋白（100mg／L）十硫酸乙酰肝素蛋白聚糖（15．5mg／L）组0及氧化型低密度脂蛋白（100mg／L）十肝素（200mg／L）组巨噬细胞内红色颗粒明显少于氧化型低密度脂蛋白组；氧化型低密度脂蛋白十硫酸乙酰肝素蛋白聚糖组及氧化型低密度脂蛋白十肝素组巨噬细胞内总胆固醇和胆固醇酯的含量明显低于氧化型低密度脂蛋白组（P＜0．05，P＜0．01）；硫酸乙酰肝素蛋白聚糖组及肝素组125Ⅰ标记的氧化型低密度脂蛋白降解量均低于对照组。结果提示，硫酸乙酰肝素蛋白聚糖和肝素可能是通过下调清道夫受体活性减少了巨噬细胞对氧化型低密度脂蛋白的摄取而抑制脂质在巨噬细胞内的聚集和泡沫细胞的形成。     

表皮生长因子受体抑制剂与肺纤维化

酪氨酸蛋白激酶(tyrosine protein kinase，TPK)是一类能催化蛋白质酪氨酸磷酸化的蛋白激酶，其活性最早是在癌基因src产物上发现的。该酶能催化ATP的γ磷酸基转移到自身或底物的酪氨酸残基上，使酚羟基磷酸化，通过蛋白质磷酸化的级联反应传递信息，导致生物效应。酪氨酸蛋白激酶介导的细胞内信号传导TPK为一个大的结构多样的酶家族，分为受体型和非受体型两种。受体型TPK(receptor tyrosine kinase，RTK)是细胞内段具有酪氨酸激酶活性的一类跨膜受体，如血小板衍生生长因子受体(PDGFR)、成纤维细胞生长因子受体(FGFR)、表皮细胞生长因子受体(EGFR)等，非受体型TPK是细胞浆中具有酪氨酸激酶活性的蛋白质。     

CD36介导氧化型低密度脂蛋白诱导U937细胞泡沫化和凋亡

为探讨清道夫受体ＣＤ３６在氧化型低密度脂蛋白诱导Ｕ９３７细胞泡沫化和凋亡中的作用,用氧化型低密度脂蛋白温育Ｕ９３７细胞,观察Ｕ９３７细胞泡沫化过程中ＣＤ３６的表达时序和泡沫细胞的凋亡;用ＣＤ３６单克隆抗体阻断Ｕ９３７细胞的吞噬作用,观察Ｕ９３７细胞吞噬蓄积胆固醇和细胞凋亡的改变。细胞胆固醇以修饰的酶荧光法测定;用流式细胞术检测异硫氰酸荧光素－抗ＣＤ３６单克隆抗体特异标记的ＣＤ３６和细胞的凋亡情况;用逆转录聚合酶链反应检测ＣＤ３６ｍＲＮＡ的表达。结果发现,８０ｍｇ／Ｌ氧化型低密度脂蛋白与Ｕ９３７细胞温育２４ｈ可增加细胞内总胆固醇,４８ｈ时可形成典型的泡沫细胞;ＣＤ３６表达呈现时序性改变,６ｈ即可检出ＣＤ３６表达增高,２４ｈ达到最高值,４８ｈ表达略有降低,ＣＤ３６ｍＲＮＡ的转录与ＣＤ３６的表达一致。用２００ｍｇ／Ｌ     

趋化因子CXC配体16的生物学效应研究进展

能与磷脂酰丝氨酸和氧化型低密度脂蛋白结合的清道夫受体和趋化因子CXC配体16是同一种基因的不同命名。该蛋白质属于CXC家族,主要在抗原呈递细胞、平滑肌细胞、内皮细胞和T细胞中表达。作为清道夫受体,它以跨膜结合型存在,能与氧化型低密度脂蛋白结合。可能参与了巨噬细胞源性泡沫细胞的形成,导致动脉粥样硬化。作为趋化因子,它以分泌型存在时,主要在免疫系统、中枢神经系统和肿瘤等方面起重要作用。     

CD36与动脉粥样硬化

CD36是在多种组织细胞上表达的跨膜糖蛋白,属于B族清道夫受体.单核巨噬细胞上的CD36是吞噬摄取氧化型低密度脂蛋白的主要受体.除介导泡沫细胞形成外,CD36还有促进凝血和单核细胞聚集,促进炎症反应和氧化、凋亡等多种功能,其表达可被高度调控,是巨噬细胞泡沫化和动脉粥样硬化发生发展的重要因素.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis： Randomized,placebo-controlled pilot study

AIM： To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine （NAC） co-administration with mesalamine in ulcerative colitis （UC） patients.
METHODS： Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine （2.4 g/d） plus N-acetyl-L-cysteine （0.8 g/d） （group A） or mesalamine plus placebo （group B）. Patients were monitored using the Modified Truelove-Witts Severity Index （MTWSI）. The primary endpoint was clinical remission （MTWSI ≤ 2） at 4 wk. Secondary endpoints were clinical response （defined as a reduction from baseline in the MTWSI of ≥ 2 points） and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS： Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine （group A） and mesalamine plus placebo （group B） respectively （OR = 1.71; 95% CI： 0.46 to 6.36; P = 0.19; NNT = 7.7）. Analysis of variance （ANOVA） of data indicated a significant reduction of MTWSI in group A （P = 0.046） with respect to basal condition without significant changes in the group B （P = 0.735） during treatment. Clinical responses were 66% （group A） vs 44% （group B） after 4 wk of treatment （OR = 2.5; 95% CI： 0.64 to 9.65; P = 0.11; NNT = 4.5）. Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.
CONCLUSION： In group A （oral NAC combined with mesalamine） contrarily to group B （mesalamine alone）, the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.     

Delorme's transrectal excision for internal rectal prolapse

Surgical therapy of functional outlet obstruction in patients with internal rectal intussusception may include abdominal, perineal, or transrectal procedures. Because abdominal procedures often result in significant physiologic impact but unrelieved constipation, the authors have elected Delorme's transrectal excision for management of these patients. Since a short-term placebo effect attends many therapies, this report describes results of transrectal excision only after a threeyear postoperative period. Delorme's transrectal excision of internal intussusception accomplished sustained symptomatic relief in over 70 percent of otherwise refractory constipated patients. The association of internal intussusception with other abnormalities underscores the importance of defining both anatomic and functional components when selecting patients whose constipation may require surgical therapy. Critical technical elements, surgical pitfalls, and potential complications of the procedure are discussed.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.     

The oral glucose tolerance test: A comparison of the time points on the basis of limit values,normal dispersion,and reproducibility

Summary Time points in the glucose tolerance test (GTT) are compared on the basis of limit values, dispersion within a reference population, and reproducibility. We suggest using the distance between a limit value and the median reference value as a measure of the magnitude of abnormality. The distance between 140 mg/100 ml and the median fasting plasma glucose value is chosen as a standard distance and limits for other points in the GTT are calculated to equal this standard distance of abnormality. We suggest that the probability of correctly interpreting an inividual result is directly related to the reproducibility of the test and inversely related to the percentage of the total range of values which is dispersed among the normal population. The ratio of reproducibility to percentage normal dispersion is proposed as an index of the probability of correctly interpreting an individual result. According to this index, the probability of correct interpretation varies in order: fasting plasma glucose concentration>3-h>2-h>0.5-h>1-h plasma glucose concentration.