Hypermethylation of the 5' region of the calcitonin gene is a property of human lymphoid and acute myeloid malignancies

An abnormal increase in numbers of CCGG sites methylated in the 5' region of the human calcitonin (CT) gene occurred in tumor cell DNA samples from 90% (17 of 19) of patients with non-Hodgkin's T and B cell lymphoid neoplasms and in 95% (21 of 22) of tumor cell DNA samples from patients with acute nonlymphocytic leukemia (ANLL). The changes were not seen in patients with chronic myelogenous leukemia (0 of 9). The abnormal methylation patterns appear to be a property only of transformed or malignant cells since they were not found in DNA from nonneoplastic adult tissues including sperm, early myeloid progenitor cells, benign lymphoid hyperplasia, peripheral lymphocytes stimulated to divide, or early myeloid progenitor cells (obtained by immunoaffinity using anti-My-10 antibody), but they did appear after Epstein-Barr virus transformation of lymphocytes. Moreover, during the course of therapy in patients with ANLL, the hypermethylation pattern reflects the presence of the leukemic clone even in normal-appearing granulocytes derived from this clone. The increased methylation of the CT gene may then provide an important molecular marker for biologic events in human cell transformation or tumor progression and may prove clinically useful in monitoring patients with lymphoid and acute myelogenous neoplasms.     

唇腭裂患者AF-BF距及AXB角的测量分析

目的 研究唇腭裂患者AF-BF距和AXB角.方法 选取20例替牙期及30例恒牙期唇腭裂患者拍摄头颅定位侧位X线片,测量其AF-BF距及AXB角与北京市同龄、同性别正常儿童、青少年的AF-BF距及AXB角值进行比较.结果 替牙期和恒牙期唇腭裂患者AF-BF距及AXB角值无性别差异(P > 0.05).新疆地区替牙期和恒牙期唇腭裂患者AF-BF距小于北京市正常儿童、青少年(P < 0.05),而AXB角值差异无统计学意义(P > 0.05).结论 AF-BF距可以作为评价唇腭裂患者上下颌骨间矢状关系的指标之一,但最好进行综合分析.     

Pathologic effects of plasma from patients with thrombotic thrombocytopenic purpura on platelets and cultured vascular endothelial cells

The pathologic hallmarks of thrombotic thrombocytopenic purpura (TTP) include endothelial cell proliferation and subendothelial hyalin deposits in the microvasculature leading to symptomatic thrombotic occlusions. Plasma or sera from three consecutive patients with TTP were subjected to multiple analyses to determine whether they induce endothelial injury and/or platelet activation, two pathogenic mechanisms that may account for this disorder. Sera were utilized in a microcytotoxicity assay against cultured human umbilical vein endothelial cells (EC). These cells were assessed ultrastructurally and with immunofluorescence techniques to ascertain the nature of inflicted cell damage. Control plasmas were obtained from healthy volunteers as well as patients with immune complex disease and the adult hemolytic uremic syndrome. In the presence of TTP serum, cell kill of 3H-proline- labeled EC averaged 42% versus 8.6% for control sera. Cytotoxicity induced by an IgG fraction of TTP sera averaged 70% versus 16.8% for control IgG. Removal of IgG by immune precipitation diminished cytotoxicity by 70%. Using indirect immunofluorescence, IgG was detected on EC incubated with TTP serum but not on EC treated with control serum. Ultrastructural changes became apparent within 30 min after exposure of cultured EC to TTP serum. Virtually every cell developed numerous cytoplasmic inclusions rarely seen in EC in the presence of normal serum. Prolonged incubation with the TTP serum led to progressive cytolysis, terminating with complete cytoplasmic and nuclear degeneration. Plasma from all three patients with TTP caused spontaneous aggregation of normal washed platelets as monitored by aggregometry. No spontaneous aggregation occurred in response to control plasmas. These results indicate that the sera of the three TTP patients studied were able to mediate time-dependent immune destruction of human cultured endothelial cells and that their plasmas were capable of causing spontaneous aggregation of normal human platelets in vitro. It would seem likely that these mechanisms are also operative in vivo to produce the endothelial destruction as well as the thrombotic vascular occlusions seen in this disorder.     

绝经前后女性冠心病患者HDL及LDL颗粒与冠状动脉病变程度的相关性研究

目的探讨绝经前后女性冠心病患者高密度脂蛋白(HDL)颗粒及低密度脂蛋白(LDL)颗粒与冠状动脉病变程度的关系。方法收集经冠状动脉造影确诊的女性冠心病患者79例,根据是否绝经分为绝经前组(n=37)和绝经后组(n=42)。Lipoprint脂蛋白分析仪对HDL颗粒及LDL颗粒进行检测分析,探讨两种脂蛋白颗粒与冠状动脉病变程度的关系。结果与绝经前组比较,绝经后组大颗粒HDL浓度(102.6±45.2 mg/L比143.8±49.7 mg/L,P0.05)及所占比例(23.34%±8.26%比31.15%±7.98%,P0.05)、LDL颗粒平均直径(259.5±8.1比265.7±3.7,P0.05)均降低,小颗粒HDL浓度(124.0±76.8 mg/L比87.0±34.9 mg/L,P0.05)及所占比例(27.26%±12.34%比18.62%±6.53%,P0.05)、LDL B型比例(73.8%比48.6%,P0.05)、Gensini积分(50.88±26.46比30.43±18.54,P0.05)均增高。绝经前组及绝经后组多支病变患者大颗粒HDL浓度、LDL颗粒平均直径均低于单支病变患者,Gensini积分高于单支病变患者;绝经后组大颗粒HDL浓度、LDL颗粒平均直径均低于绝经前组,小颗粒HDL所占比例及Gensini积分高于绝经前组。绝经前组和绝经后组LDL颗粒大小及大颗粒HDL浓度均与Gensini积分呈负相关。结论与绝经前组相比,绝经后组大颗粒HDL浓度较低,小颗粒HDL浓度较高,LDL颗粒平均直径较小,冠状动脉病变程度较严重;大颗粒HDL浓度及LDL平均直径与冠状动脉病变严重程度明显相关。     

IgA肾病血尿误诊为尿路感染血尿三例分析

目的 探讨IgA肾病的病理特点,提高诊断合格率.方法 回顾性分析3例有血尿症状的IgA肾病患者被误诊为尿路感染血尿的经过和原因.结果 3例患者均为系膜增生性IgA肾病患者,HaasⅠ级2例、HaasⅡ级1例,均于发病前出现过尿路感染,确诊后均已治愈.结论 IgA肾病的复杂性和隐匿性使其易被误诊,临床诊断要全面掌握IgA肾病的临床与病理特点,不能局限于表面症状的诊断.     

Recipient humoral immunity against leukoreduced allogeneic platelets is suppressed by aminoguanidine, a selective inhibitor of inducible nitric oxide synthase

Leukoreduced allogeneic platelet transfusions have been previously shown to initially stimulate an in vitro cellular cytotoxicity and subsequently Induce the formation of immunoglobulin G (IgG) antidonor alloantibodies. To further characterize these responses and determine if they are related, recipient BALB/c H-2d mice were treated with aminoguanidine (AMG), a selective inhibitor of inducible nitric oxide synthase (iNOS), and transfused weekly with 2 x 10(8) C57BL/6 H2b platelets. In control, non-AMG-treated mice, transfusion significantly (P < .01) increased serum levels of interferon-gamma (IFN-gamma) by day 1 posttransfusion (PT). IFN-gamma returned to pretransfusion levels by day 3 PT, and its production was not affected by AMG treatment. Serum interleukin-4 (IL-4), on the other hand, was undetectable before and during the transfusion protocol. By day 3 PT, recipient spleen cells could mediate in vitro anti-P815 (auto), anti-EL4 (allo), and anti-R1.1 (third-party MHC) cytotoxicity, and these responses were maximal by day 7 PT. Concurrently, a significant reduction in the vitro ability of recipient splenocytes to respond to Concanavalin A (ConA) was observed; this was not seen with lipopolysaccharide (LPS) stimulation. Elevated levels of NO2- were found in the ConA culture supernatants from transfused mice at day 3 PT. Serum antidonor alloantibodies were detected by the fifth platelet transfusion. AMG treatment of recipient mice significantly inhibited the transfusion. Induced cytotoxicity and ConA-stimulated NO2- production, and restored ConA-induced proliferation to normal levels. AMG appeared to selectively inhibit platelet-induced alloantibody production in that it did not affect antibody production induced by transfusions with 10(5) allogeneic leukocytes or by immunization with a foreign protein antigen, human gamma globulin, in adjuvant therapy. These results indicate that an in vivo AMG-sensitive mechanism is essential for recipients to initiate a humoral IgG immune response against allogeneic platelets.     

Platelet modulation of polymorphonuclear leukocyte shear induced aggregation

A cone and plate viscometer and Coulter Counter were used to study platelet modulation of polymorphonuclear leukocyte (PMNL) aggregation caused by controlled shear stress. As an index of aggregation, the large-particle percentage (LPP) was calculated. This represents the ratio of aggregated cell count to total cell count. PMNL suspensions in buffer (1.0 X 10(7) cells per milliliter, final concentration) did not show any aggregate formation at shear stresses below 150 dynes/cm2 for one minute exposure time (LPP less than 3%). However, there was PMNL aggregation in mixed PMNL and platelet-rich plasma suspensions in this shear stress range. Supernatant plasma from sheared platelets initiated PMNL aggregation at moderate shear stress (150 dynes/cm2 for one minute; LPP, 20.3% +/- 2.5%). In contrast, platelet release factors, such as adenosine diphosphate (2 mumol/L) and serotonin (2 mumol/L) did not cause PMNL aggregation (LPP, 2.9% +/- 1.2% and 3.3% +/- 0.8%, respectively). The use of a cyclo-oxygenase inhibitor (acetylsalicylic acid, 50 mumol/L) did not suppress the aggregation of PMNLs after shear (LPP, 20.1% +/- 2.4%). However, preincubation with nordihydroguaiaretic acid (10 mumol/L), an inhibitor of C-5 and C-12 lipoxygenase, and 6,9- deepoxy-6,9-(phenylimino)-6,8-prostaglandin I1 (U-60257, 10 mumol/L), an inhibitor of C-5 lipoxygenase in human leukocytes, suppressed this aggregation (LPP, 9.1% +/- 2.5% and 10.4% +/- 3.2%, respectively). Also, the formation of lipoxygenase products (5-HETE, 12-HETE, 15-HETE, and LTB4) activated by shear stress was documented by reversed phase- high-performance liquid chromatography (RP-HPLC). These data support the possibility of a cooperation between platelets and leukocytes in shear-induced PMNL aggregation that is dependent on C-12 or C-5 lipoxygenase activity, or both.     

Thrombolytic therapy with tissue plasminogen activator or streptokinase induces transient thrombin activity

We have determined the plasma level of fibrinopeptide A as a specific index of thrombin activity during the infusion of a thrombolytic agent in patients with acute myocardial infarction. Peripheral venous plasma levels of fibrinopeptide A increased following the initiation of thrombolytic therapy from 2.7 nmol/L to a peak of 13.0 nmol/L at 30 minutes with streptokinase and from 1.1 nmol/L to a peak of 10.7 nmol/L at 90 minutes with tissue plasminogen activator. The amount of fibrinogen converted to fibrin I was determined by integration of the plasma level of fibrinopeptide A over time. The amount of fibrin I formed over the five-hour period from the start of drug infusion was approximately 10 mg/dL in response to either streptokinase or recombinant tissue plasminogen activator. We conclude that activation of coagulation occurs in response to thrombolytic therapy despite heparin administration. This thrombin action, though transient, would be sufficient to cause rethrombosis if localized and incompletely opposed by fibrinolytic activity.     

自体富血小板血浆对Stanford A型主动脉夹层手术中输血和短期转归的影响

目的观察自体富血小板血浆(autologous platelet-rich plasma,aPRP)对深低温停循环(deep hypothermic circulatory arrest,DHCA)下的Stanford A型主动脉夹层手术中输血量和术后短期转归的影响。方法选择2016年6月至2017年8月在本院接受手术治疗的急性Stanford A型主动脉夹层患者83例,男60例,女23例,年龄24～81岁,BMI 19.0～41.9kg/m2,ASAⅣ级。根据是否制备aPRP将患者分为观察组(n=35)和对照组(n=48)。两组患者于麻醉诱导插管后经右侧颈内静脉置入三腔中心静脉导管和Swan-Ganz导管外鞘。随后,观察组于手术开始前完成aPRP制备,对照组开始手术。记录麻醉、手术、心肺转流(cardiopulmonary bypass,CPB)、主动脉阻断和DCHA时间。记录血栓弹力图反应时间(R)、α角和最大振幅(MA);记录术中出血量和红细胞、血浆、冷沉淀和血小板用量;记录术后机械通气时间、ICU留观时间、30d内严重并发症(神经系统并发症、需要持续肾脏替代治疗的急性肾功能不全、二次插管或气管切开、胸骨后感染或胸骨愈合不良、开胸止血)发生率和死亡率。结果观察组手术时间明显短于对照组(P0.05)。麻醉、CPB、主动脉阻断时间差异无统计学意义。观察组DCHA时间明显短于对照组(P0.05)。观察组TEGα角和MA明显大于对照组(P0.05)。观察组术中红细胞、血浆和冷沉淀用量明显少于对照组(P0.05)。两组术后机械通气时间、ICU留观时间、术后30d严重并发症发生率和死亡率差异无统计学意义。结论在DCHA下的Stanford A型主动脉夹层手术,aPRP可减少术中红细胞、血浆和冷沉淀的用量,但对术后机械通气时间、ICU时间、术后30d内严重并发症发生率和死亡率无明显影响。     

Lithium augments GM-CSA generation in canine cyclic hematopoiesis

Cyclic hematopoiesis in gray collie dogs can be cured by lithium treatment. We examined the mechanism of lithium's effect by developing an assay for the canine equivalent of GM-CSF (called GM-CSA). Phytohemagglutinin (PHA)-stimulated canine blood mononuclear cells produce GM-CSA in a dose-dependent manner; this GM-CSA stimulates more neutrophil-containing colonies than does endotoxin-treated dog serum. Production of GM-CSA by PHA-stimulated normal dog cells was not altered by lithium. However, cells from gray collies during their neutrophilic period increased their GM-CSA when lithium (2 mEq/L) was added to low doses of PHA, whereas neutropenic gray collie cells did not. These data suggest that lithium could modulate cyclic hematopoiesis by increasing intramedullary GM-CSA at the time when marrow neutrophilic progenitor cells are at their nadir.