间质干细胞与免疫调节

目的:间质干细胞能够逃避免疫识别,抑制免疫反应特征。文章就近年来间质干细胞及其免疫调节作用进行综述。资料来源:应用计算机检索PUBMED 1976-01/2006-01期间的相关文章,检索词为"mesenchymal stem cells,immune modulation",并限定文章语言种类为English。资料选择:对资料进行初审,并查看每篇文献后的引文。纳入标准:文章所述内容应与间质干细胞及其免疫调节作用相关。排除标准:重复研究或Meta分析类文章。资料提炼:共收集到263篇相关文献,68篇文献符合纳入标准,排除的195篇文献为内容陈旧或重复。符合纳入标准的68篇文献中,分别涉及间质干细胞的免疫原性、免疫抑制作用及机制、应用等内容。资料综合:间质干细胞广泛存在于各种组织中,本身具有免疫原性低的特点,可以逃避同种异基因免疫识别。间质干细胞在体外、体内均有明确的免疫抑制作用,与间质干细胞对树突状细胞、T细胞、自然杀伤细胞等的调控作用有关。间质干细胞尚可对转化生长因子、白细胞介素、基质细胞来源因子、NF-κB配体、前列腺素、吲哚胺2,3-二氧酶等可溶性因子产生影响。由于间质干细胞多方面的免疫调节活性,使其拥有良好的应用前景,目前已在移植物抗宿主病及自身免疫疾病的治疗中发挥了作用。结论:间质干细胞无论在体内或体外均对T细胞的活化有抑制作用,可调节在同种异体抗原的识别和清除过程中主要细胞群的免疫功能,包括抗原递呈细胞、T细胞和自然杀伤细胞,但其调节免疫抑制作用的分子机制尚未被完全阐明。     

山东沿海地区高尿酸血症患者SLC22A12基因的多态性

目的:观察山东沿海地区人群SLC22A12基因的多态性,分析其与高尿酸血症的关系。方法:该实验于2005-11/2006-04收集病历于2006-05/07完成实验室部分。纳入青岛大学医学院附属医院门诊或青岛市社区高尿酸血症患者138例为高尿酸血症组,同时选取青岛市区健康者117人健康对照组。两次来访,初访时进行详细的记录,包括用药情况、身高、体质量、腰围、腹围、体质量指数、血压以及家族史。再访时隔夜空腹12h抽血测血尿酸、血糖、血脂、肝酶等,分析两组生化指标的差异。所有标本采用PCR、DNA序列分析、病历对照等方法对138例高尿酸血症者和117例健康对照者基因进行分析。结果:高尿酸血症组患者138例,健康对照组117人全部进入结果分析,无脱失。①健康对照组和高尿酸血症组一般情况比较,年龄、血肌酐、空腹血糖两组比较差异无统计学意义(P>0.05)。体质量指数、腰臀围比、血压、血尿酸、总胆固醇、三酰甘油空腹血糖两组比较差异有显著性意义(P<0.001)。②健康对照组CC CT基因型和TT基因型频率与高尿酸血症组比较差异有非常显著性意义(77.8%,97.1%;22.2%,2.9%;P<0.001)。③健康对照组CC CT基因型和TT基因型相对应的血尿酸值比较差异有显著性意义[(271±33.5),(301±37.8)mmol/L,P<0.01]。高尿酸血症组CC CT基因型和TT基因型相对应的血尿酸比较差异无统计学意义[(457±71.2),(459±80.1)mmol/L,P>0.05]。结论:高尿酸血症和正常人hURAT1基因同样存在多个突变位点,基因的多态性与血清尿酸水平有关。SLC22A12基因C258T位点多态性与中国沿海地区高尿酸血症有关。     

An unusual case of autoimmune hemolytic anemia with reticulocytopenia, erythroid dysplasia, and an IgG2 autoanti-U

BACKGROUND: Autoantibodies with anti-U specificity, usually in combination with autoantibodies of other specificities, have occasionally been identified in association with autoimmune hemolytic anemia. A case of life-threatening autoimmune hemolytic anemia, characterized by several atypical features, including apparent intravascular hemolysis associated with an IgG2 anti-U, reticulocytopenia, and bone marrow dyserythropoiesis is described. CASE REPORT: A 36-year-old man with a severe case of acute-onset autoimmune hemolytic anemia was admitted to another hospital; he had a hematocrit of 15 percent, elevated bilirubin and lactate dehydrogenase, and positive direct and indirect antiglobulin tests. He received 7 units of incompatible red cells without improvement in hematocrit, and he was transferred to University Hospitals of Cleveland (OH). He was jaundiced and became syncopal in the sitting position. His serum was reddish pink; he had a hematocrit of 11.8 percent and a reticulocyte count of 2.5 percent. No spherocytes were observed in the peripheral blood smear. Shortly after admission, the hematocrit fell to 6.9 percent. He was given 3 units of “least-incompatible” red cells and was started on prednisone, with little improvement. An IgG2 autoanti-U was detected in his serum. Seven units of U- red cells were transfused over the next 4 days. The hematocrit improved to 23 percent and continued to rise without further transfusion. A bone marrow examination, initially revealing erythroid hyperplasia accompanied by dyserythropoiesis, became morphologically normal. Drug studies failed to show evidence of drug-related hemolysis. He remains well 2 years after discharge without evidence of recurrent hemolysis. CONCLUSION: Severe life-threatening autoimmune hemolytic anemia, in this instance induced by an autoanti-U, may be associated with IgG2 autoantibody and characterized by apparent intravascular hemolysis and bone marrow dyserythropoiesis. Early treatment with U- blood, in addition to steroids, may be beneficial.     

Fibrin sheath enhances central venous catheter infection

OBJECTIVE: To determine whether fibrin-coated central venous catheters have a higher infection rate, and spawn more septic emboli, than uncoated catheters after exposure to bacteremia. DESIGN: Animal study comparing catheter infection and blood cultures of fibrin-coated and uncoated catheters exposed to bacteremia. SETTING: Animal laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: A total of 210 rats had catheters placed with the proximal end buried subcutaneously. Rats were divided into three groups: tail vein bacterial injection on day 0 (no fibrin group) or on day 10 (fibrin group), or no injection/saline injection (control, n = 40). Bacterial injections were 1 x 108 colony forming units of either Staphylococcus epidermidis (n = 100) or Enterobacter cloacae (n = 60). Animals were killed 3 days after injection. Blood cultures were obtained via cardiac puncture, and catheters were removed via the chest. Half of the catheter was rolled onto agar and the other half was placed in trypticase soy broth. Plates and broth were incubated at 37 degrees C for 48 hrs. The presence of >15 colonies on roll plates, or growth in broth, was accepted as a positive sign of infection. Microscopy was performed on day 20-10 catheters. Thirty animals without catheters had bacterial injections and underwent blood culture 3 days after injection. MEASUREMENTS AND MAIN RESULTS: Catheter infection with S. epidermidis occurred in 32% of roll plates and 80% of broth from the fibrin group vs. 4% and 20% from the no fibrin group (p <.01 for each). Catheter infection with E. cloacae occurred in 50% of roll plates and 80% of broth from the fibrin group vs. 0% and 12% from the no fibrin group (p <.01 for each). Positive blood cultures occurred in 47 of 68 animals from the fibrin group vs. 8 of 68 from the no fibrin group (p <.01). Microscopy showed a fibrin sheath on 20 of 20 catheters. Without catheters, 30 of 30 blood cultures were negative. CONCLUSION: The fibrin sheath significantly enhanced catheter-related infection and persistent bacteremia.     

Corticotrophin releasing hormone levels in human plasma and amniotic fluid during gestation

OBJECTIVE Corticotrophin releasing hormone, a hypothalamic neuropeptide also made in placenta, may regulate fetal maturation in a stress-responsive manner. The objectives of this study were: (1) to determine if levels of corticotrophin releasing hormone in the amniotic fluid correlate with fetal lung maturation; (2) to confirm that third trimester plasma levels of corticotrophin releasing hormone are increased in patients with pregnancy-induced hypertension compared to normotensives, and (3) to increase the recovery of extracted corticotrophin releasing hormone from plasma and amniotic fluid. DESIGN (1) Levels of corticotrophin releasing hormone in amniotic fluid during the third trimester were compared with those of saturated phosphatidyl choline. (2) Corticotrophin releasing hormone levels were measured in a group of normotensive pregnant women during the entire gestation period. Corticotrophin releasing hormone levels during the third trimester were compared in normotensives and patients with pregnancy-induced hypertension. PATIENTS Twenty-one non-pregnant normal volunteers and 63 pregnant women. MEASUREMENTS Blood pressure, corticotrophin releasing hormone in plasma and amniotic fluid, and saturated phosphatidyl choline in amniotic fluid. RESULTS Corticotrophin releasing hormone levels in amniotic fluid samples during the third trimester ranged from 12 to 98 pmol/l and positively correlated with the saturated phosphatidyl choline levels, but not with gestational age. A significant difference existed in plasma corticotrophin releasing hormone concentration between gestational age-matched third trimester normotensive and hypertensive gravids: corticotrophin releasing hormone levels were significantly lower in normotensives (223 ± 65 pmol/l) than in patients with pregnancy-induced hypertension (544 ± 106 pmol/l, P= 0.001). Plasma corticotrophin releasing hormone increased with gestational age from 51 pmol/l (range 8.4–85) at 25–32 weeks to 375 pmol/l (range 35–1386) at 33–40 weeks. During the third trimester the rise in plasma corticotrophin releasing hormone conformed to an exponential mathematical model of a positive feedback loop between placental corticotrophin releasing hormone and fetal adrenal Cortisol. CONCLUSIONS During the third trimester of pregnancy there is a positive correlation between the level of amniotic fluid corticotrophin releasing hormone and that of saturated phosphatidyl choline. The positive correlation between amniotic fluid corticotrophin releasing hormone and saturated phosphatidyl choline, but not between amniotic fluid corticotrophin releasing hormone and gestational age, suggests that a factor(s), such as stress, may affect both amniotic fluid corticotrophin releasing hormone and saturated phosphatidyl choline in parallel. Furthermore, our data are consistent with the hypothesis that the rise in placental corticotrophin releasing hormone is coupled to an increase in fetal glucocorticoid and lung maturation, and that stresses such as pregnancy-induced hypertension may accelerate this process.     

EUS-guided fine needle aspiration of pancreatic cysts: a retrospective analysis of complications and their predictors.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine-needle aspiration (EUS FNA) of pancreatic cysts is considered safe, however, data are conflicting regarding complication rates. The aim of this study was to determine the complication rate of EUS-guided pancreatic cyst aspiration and predictors of these complications. METHODS: Results of pancreatic cyst EUS FNA at 2 academic institutions from March 1996 to October 2003 were reviewed. A total of 603 patients with 651 pancreatic cysts were evaluated. Complications were identified from clinic, emergency department, and discharge notes, and laboratory and radiologic data. Data collected were as follows: cyst size, location, septations, diagnosis, number of passes, needle size, status as inpatient or outpatient, performance of same-day endoscopic retrograde cholangiopancreatography (ERCP), and use of prophylactic antibiotics. RESULTS: Complications were identified in 13 patients (2.2%, 13 of 603): 6 patients had pancreatitis, 4 patients had abdominal pain, 1 patient had a retroperitoneal bleed, 1 patient had an infection, and 1 patient had bradycardia. Twelve patients required hospitalization, with an average length of stay of 3.8 +/- 1.1 days. Type of cyst, size, presence of septations or mass, and same-day ERCP were not predictors of complications. CONCLUSIONS: EUS-guided pancreatic cyst aspiration carries a low complication rate similar to that reported for solid pancreatic lesions. No patient or cyst characteristics appear to be predictive of adverse events.     

Laparoscopic Features and Repair of a Combined left Spigelian Hernia and left Morgagni Diaphragmatic Hernia

Both Spigelian and Morgagni hernias cause serious morbidity so early diagnosis and timely treatment are necessary. These two types of hernia are more commonly found on the right side of patients. They are rare individually in adults and even rarer in combination. So far, an association between the two hernias has only been reported on the right. We describe the first case of a Spigelian hernia and a Morgagni hernia in a 62-year-old woman, both occurring on the left side. Our accompanying video describes several laparoscopic features that will help lead to early detection and diagnosis.     

The effect of inflammatory cell-derived MCP-1 loss on neuronal survival during chronic neuroinflammation

Intracranial implants elicit neurodegeneration via the foreign body response (FBR) that includes BBB leakage, macrophage/microglia accumulation, and reactive astrogliosis, in addition to neuronal degradation that limit their useful lifespan. Previously, monocyte chemoattractant protein 1 (MCP-1, also CCL2), which plays an important role in monocyte recruitment and propagation of inflammation, was shown to be critical for various aspects of the FBR in a tissue-specific manner. However, participation of MCP-1 in the brain FBR has not been evaluated. Here we examined the FBR to intracortical silicon implants in MCP-1 KO mice at 1, 2, and 8 weeks after implantation. MCP-1 KO mice had a diminished FBR compared to WT mice, characterized by reductions in BBB leakage, macrophage/microglia accumulation, and astrogliosis, and an increased neuronal density. Moreover, pharmacological inhibition of MCP-1 in implant-bearing WT mice maintained the increased neuronal density. To elucidate the relative contribution of microglia and macrophages, bone marrow chimeras were generated between MCP-1 KO and WT mice. Increased neuronal density was observed only in MCP-1 knockout mice transplanted with MCP-1 knockout marrow, which indicates that resident cells in the brain are major contributors. We hypothesized that these improvements are the result of a phenotypic switch of the macrophages/microglia polarization state, which we confirmed using PCR for common activation markers. Our observations suggest that MCP-1 influences neuronal loss, which is integral to the progression of neurological disorders like Alzheimer's and Parkinson disease, via BBB leakage and macrophage polarization.     

Fulminant hepatic failure secondary to amebic abscesses

Summary A patient presented with fulminant hepatic failure which rapidly led to his death. At postmortem examination, he had several amebic abscesses secondarily infected with bacteria, one of which had ruptured intraperitoneally, and another of which had occluded major hepatic veins of the right lobe of the liver. In addition, pylephlebitis and occlusion of several right portal venous radicies were noted. Microscopic examination of the right lobe revealed marked sinusoidal congestion and large areas of infarction with severe panlobular necrosis. Fuiminant hepatic failure secondary to complications of amebic abscess has been reported infrequently but should be considered in patients with this presentation who have visited or inhabited areas endemic for amebiasis.     

Binge eating disorder in extreme obesity

OBJECTIVE: To determine whether extremely obese binge eating disorder (BED) subjects (BED defined by the Eating Disorder Examination) differ from their extremely obese non-BED counterparts in terms of their eating disturbances, psychiatric morbidity and health status. DESIGN: Prospective clinical comparison of BED and non-BED subjects undergoing gastric bypass surgery (GBP). SUBJECTS: Thirty seven extremely obese (defined as BMI > or = 40 kg/m(2)) subjects (31 women, six men), aged 22-58 y. MEASUREMENTS: Eating Disorder Examination 12th Edition (EDE), Three Factor Eating Questionnaire (TFEQ), Structured Clinical Interview for the Diagnostic and Statistical Manual-IV (SCID-IV), Short-Form Health Status Survey (SF-36), and 24 h Feeding Paradigm. RESULTS: Twenty-five percent of subjects were classified as BED (11% met full and 14% partial BED criteria) and 75% of subjects were classified as non-BED. BED (full and partial) subjects had higher eating disturbance in terms of eating concern and shape concern (as found by the EDE), higher disinhibition (as found by the TFEQ), and they consumed more liquid meal during the 24 h feeding paradigm. No difference was found in psychiatric morbidity between BED and non-BED in terms of DSM-IV Axis I diagnosis. The health status scores of both BED and non-BED subjects were significantly lower than US norms on all subscales of the SF-36, particularly the BED group. CONCLUSION: Our findings support the validity of the category of BED within a population of extremely obese individuals before undergoing GBP. BED subjects differed from their non-BED counterparts in that they had a greater disturbance in eating attitudes and behavior, a poorer physical and mental health status, and a suggestion of impaired hunger/satiety control. However, in this population of extremely obese subjects, the stability of BED warrants further study.