Serotonin transporter characteristics in lymphocytes and platelets of male aggressive schizophrenia patients compared to non-aggressive schizophrenia patients

A large body of literature indicates that disturbances of central serotonin (5-HT) function play an important role in aggressive behavior. Results from open-label and placebo-controlled trials as well as the reported inverse relationship between 5-HT function and aggression in human subjects, suggest that reduced 5-HT activity is associated with aggressive behavior. The activity of the 5-HT transporter (5-HTT), as determined by [³H]5-HT uptake to blood lymphocytes, was measured in 20 currently aggressive and 20 non-aggressive male schizophrenia patients. In addition, the pharmacodynamic characteristics of platelet 5-HTT were assessed by [³H]citalopram binding.

There were no significant differences in the density (B_max) of platelet [³H]citalopram binding sites between the two groups. Similarly, the dissociation constant (K_d) values were indistinguishable. The maximum uptake velocity (V_max) of [³H]5-HT to fresh lymphocytes and the K_m values of the 5-HT to the transporter were significantly higher in currently aggressive compared to the non-aggressive schizophrenia patients. The association of high V_max values with current aggressive behavior provides further support to the involvement of the 5-HTT in aggressive behavior as well as to the efficacy of 5-HTT blockers in the control of aggression. The role of the various components of the serotonergic system in the pathophysiology and treatment of aggressive behavior in schizophrenia needs to be further evaluated.     

黄芪对新生儿脐血淋巴细胞凋亡特性的影响

目的探讨黄芪(astragalusmenbranaceus,AM)对新生儿脐血淋巴细胞凋亡的影响及其机制。方法收集并分离30例正常足月新生儿脐血单个核细胞(cordbloodmononuclearcells,CBMC),分别经(phytohemagglutinin,PHA)、PHA+IL-6和PHA+AM刺激培养48h,采用丫啶橙-溴化乙锭染色法测定细胞凋亡水平,间接免疫荧光法测定CD38+和CD25+细胞百分率,ELISA方法检测培养液上清中IL-6水平。结果(1)PHA+AM、PHA+IL-6和单纯PHA组细胞凋亡率(x±s)分别为(16．5±3．5)％、(16．9±4．0)％和(32．4±2．8)％,PHA+AM和PHA+IL-6组均明显低于单纯PHA组(q=25．16,24．54;P<0．01),而前二者间差异无统计学意义(q=0．62,P>0．05);(2)PHA+AM、PHA+IL-6和单纯PHA组CD38+细胞百分率分别为(9．8±1．8)％、(9．9±0．6)％和(22．3±1．5)％,PHA+AM和PHA+IL6组明显低于单纯PHA组(q=48．95,48．42;P<0．01),但前二者间差异无统计学意义(q=0．53,P>0．05);PHA+AM、PHA+IL-6和单纯PHA组CD25+细胞百分率分别为(83．2±2．4)％、(82．1±3．0)％和(65．8±4．9)％,PHA+AM和PHA+IL-6组明显高于单纯PHA组(q=26．60,24．86;P<0．01),而前二组间比较差异无统计学意义(q=1．74,P>0．05);CBMC中CD38+细胞百分率与细胞凋亡率呈正相关(r=0．68,P<0．01),而CD25+细胞百分率与细胞凋亡率呈负相关(r=-0．65,P<0．01);(3)PHA+AM组培养上清液中IL-6水平[(253．0±30．8)ng／L]明显高于单纯PHA组[(37．9±12．2)ng／L](t=6．50,P<0．01),CBMC凋亡率与培养上清液中IL-6浓度呈负相关(r=-0．75,P<0．01)。结论黄芪能明显抑制CBMC体外经PHA激活后的细胞凋亡,其机制可能与促进CBMC中胸腺细胞向T淋巴细胞分化、增强脐血淋巴细胞活化和增加IL-6产生水平等有关。     

灵芝孢子和破壁孢子多糖对体外培养的小鼠脾淋巴细胞及腹腔巨噬细胞免疫调节活性的比较

目的:比较体外给药时灵芝孢子多糖(Gl-SP)和灵芝破壁孢子多糖(Gl-BSP)对小鼠脾淋巴细胞及腹腔巨噬细胞免疫调节活性的影响.方法:噻唑蓝(MTT)法检测淋巴细胞增殖、混合淋巴细胞培养反应(MLR)、自然杀伤细胞(NK细胞)活性;比色分析检测巨噬细胞吞噬中性红的能力;流式细胞术测定脾T细胞亚群;ELISA法测定白细胞介素-2(IL-2)、γ干扰素(IFN-γ)含量,生物法测定肿瘤坏死因子α(TNF-α)活性,Griess法测定NO含量.结果:当质量浓度为0.2～12.8 mg/L时两种多糖均可促进淋巴细胞增殖及丝裂原诱导的淋巴细胞增殖,提高NK细胞活性,增强腹腔巨噬细胞吞噬能力并促进TNF-α和NO分泌.两种多糖均可促进MLR,在质量浓度为12.8 mg/L时,Gl-BSP促增殖作用明显强于Gl-SP,Gl-SP或Gl-BSP(0.2～12.8 mg/L)可显著增加IL-2、IFN-γ的分泌,但相同浓度的Gl-BSP增加IL-2和IFN-γ分泌的作用均强于Gl-SP.在一定的浓度范围内,两种多糖均可显著增加双向MLR反应中CD3 T、CD4 T和CD8 T细胞百分率,Gl-BSP在质量浓度为0.2～12.8 mg/L或3.2～12.8 mg/L时,增加CD4 或CD8 T细胞的作用较Gl-SP更为显著.在质量浓度为0.2～0.8 mg/L时,Gl-BSP组的CD4 T和CD8 T细胞的比值大于Gl-SP组.结论:Gl-SP和Gl-BSP在体外试验中具有相似的免疫调节活性,Gl-BSP的某些免疫调节作用强于Gl-SP.     

The monoclonal antibody GZS-1 detects a maturation-associated antigen of human spermatozoa that is also present on the surface of human mononuclear blood cells

A monoclonal antibody (GZS-1) has been generated by fusion of mouse myeloma cells with spleen cells from BALB/c mice immunised with human sperm cells. The antibody was determined to be an IgG₁. The corresponding antigen is present on the whole surface of ejaculated human spermatozoa. It is not detectable on spermatozoa of other mammalian species (rabbit, cat, dog, sheep, boar, bull, horse). In human male genital organs, immunostaining with GZS-1 is observed on sperm cells in the epididymis and the ductus deferens together with the lining epithelium of those organs. No reactivity of sperm cells or germ cell precursors in the testis has been detected. Functional tests using the antibody show a strong inhibitory effect on human sperm in the hamster egg penetration assay. Furthermore, the GZS-1 antigen is detectable on the surface of human lymphocytes and monocytes by immunogold electron microscopy and FACS analysis. By Western blotting of human sperm and seminal plasma performed under reducing conditions immunostaining was detected at 21–25, 31, 51–54, and 62 kDa. The reaction with human lymphocytes shows one major band at 62 kDa and additional bands at 31 and 54 kDa. The results suggest that the monoclonal antibody GZS-1 may recognise an antigen which is secreted from the epithelial cells of the epididymis and binds to ejaculated spermatozoa as a sperm coating antigen. This component may be involved in the capacitation of the sperm and the acrosome reaction. Molecules that are expressed both on sperm and on immunocompetent cells may be relevant for the regulation of immunological processes or for the development of the related immunological tolerance of sperm in the female reproductive tract.     

抑郁症患者细胞免疫功能的研究

目的研究抑郁症患者细胞免疫学功能。方法收集符合国际疾病分类第１０版单相抑郁症的门诊患者２７例，正常对照者２２例，采血作淋巴细胞增殖反应、自然杀伤细胞活性测定。结果抑郁症患者淋巴细胞增殖反应、自然杀伤细胞活性（效应细胞、靶细胞之比为２０∶１，１０∶１）明显低于正常对照（Ｐ＜０．０１），而与年龄、性别、病期、抑郁程度（汉密尔顿抑郁量表总分）和免疫学指标差异无显著性（Ｐ＞０．０５）。结论提示抑郁症患者细胞免疫功能低下，精神－神经－免疫系统可能存在复杂的相互联系。     

Vasopressin is located within lymphocytes in the rat spleen

Using dual antigen immunocytochemical staining with a specific antiserum for arginine vasopressin (AVP), we have detected AVP immunoreactivity in clusters of large immunoglobulin (Ig) G-containing cells, probably plasma cells, within the rat spleen, and in smaller cells which are IgG-negative. Vasopressin-positive cells were detected principally throughout the white pulp areas in the subcortical region of the spleen. IgG staining could only be detected within the cells and not on the cell surface, demonstrating that the antiserum is recognising genuine intracellular IgG and not cell surface antigens. Reversed-phase HPLC of spleen tissue extract revealed a single peak of AVP immunoreactivity which co-eluted with the standard. This is the first evidence that AVP is found within lymphocytes of the immune system and provides further information about the important interaction between the endocrine and immune systems.     

Relationship of Protein Calorie Malnutrition to Alcoholic Liver Disease: A Reexamination of Data from Two Veterans Administration Cooperative Studies

The relationship of protein calorie malnutrition (PCM) to alcoholic liver disease was studied in 666 patients enrolled in two Veterans Administration Cooperative Studies. Some findings of malnutrition could be detected early in 62% of the comparison patients (43 subjects who were alcoholic, but had not yet developed clinical or laboratory evidence of liver injury). In those who had progressed to the stage of liver injury sufficient to manifest clinical jaundice (536 patients), some findings of malnutrition were present in every patient (100%). The degree of malnutrition correlated closely with the development of all the serious complications of the liver disease (ascites, encephalopathy, and hepatorenal syndrome), as well as the overall mortality. The degree of malnutrition was also important in predicting response to some forms of treatment. When prednisolone, a catabolic adrenal steroid, was used, efficacy was independent of the level of malnutrition. However, a relationship was observed with the severity of the liver injury [quantified by the level of jaundice and coagulopathy, i.e., Maddrey's discriminant function (DF_(Maddrey))]. For prednisolone, the response was seen only when the DF was 81-100 reducing mortality 45%. When oxandrolone, an androgenic anabolic steroid treatment was given, efficacy was observed only in those with moderate malnutrition (PCM score 60–79% of normal) and maximized with adequate caloric intake reducing mortality 86%. To simplify the method of calculating the PCM score for predicting response to anabolic therapy, a multiple logistic regression model was developed from the parameters used to assess nutritional status: DF_(PCM)= 0.098 (peripheral blood lymphocytes) + 0.078 (creatinine height index). Using the DF_(PCM), oxandrolone improved survival 42% when the DF_(PCM) exceeded 6.5, but was < 11.0. These results suggest that the two DFs should be determined in patients with life-threatening alcoholic liver injury and the appropriate therapy administered based on the observed results.     

Intraepithelial lymphocytes and macrophages in the normal breast

Summary In this study the presence of intraepithelial cells within the normal breast parenchyma was investigated by electron microscopy and immunocytochemistry. Cells were observed which could be differentiated from the epithelial and myoepithelial cells by their cytoplasmic and nuclear morphology and the absence of cell junctions. Two cell types (lymphocytes and macrophages) were identified ultrastructurally and the bone marrow origin of the cells was confirmed by immunocytochemistry. The intraepithelial lymphocytes and macrophages were present in all samples irrespective of the physiological state. In the resting, pregnant, and lactating breast the majority of cells were lymphocytes while in the involuting breast there was a marked increase in the proportion of macrophages. The rarity of lymphoma of the breast may be related to the relatively small amount of lymphoid tissue present and the passive nature of the environment.     

Purine metabolism in human lymphocytes

Summary In peripheral human blood lymphocytes the uptake and metabolism of adenine, guanine, and hypoxanthine was investigated. This was achieved by incubation of purified lymphocytes with¹⁴C-purine bases, separation of cells from the incubation medium by a rapid filtration technique, and subsequent separation of the acid soluble material by thin-layer chromatography. No preferential uptake for one of the purine bases was observed. In all cases only traces of¹⁴C-purine bases not added originally and labeled nucleosides could be demonstrated. Approximately 2/3 of adenine and 1/2 of guanine or hypoxanthine were converted to nucleotides. Separation of formed nucleotides showed that adenine and guanine were metabolized mainly to their corresponding nucleotides; hypoxanthine was converted to a considerable amount to adenine nucleotides and only to a small proportion into its own nucleotides. These results demonstrate the predominance of adenine nucleotide formation in normal human lymphocytes.The study was supported by a grant of Fonds zur Förderung der wissenschaftlichen Forschung Österreichs (project No. 3038)     

人类免疫缺陷病毒-1感染者外周血单个核细胞体外培养的免疫学及病毒学特点

目的观察人类免疫缺陷病毒(HIV)感染者外周血单个核细胞(PBMC)体外培养过程中免疫学及病毒学的动态变化特点,并评价培养的细胞体系抗病毒活性。方法采集14例HIV感染者和6名健康人的PBMC,体外经多种细胞因子诱导培养,每3天观察细胞增殖情况,同时检测细胞表型、上清中细胞因子浓度和病毒载量。结果培养的健康人PBMC在(35±5)d最大增殖(61±8)倍;7例培养成功的HIV感染者PBMC在(21±6)d最大增殖(17±13)倍,另7例HIV感染者PBMC培养失败;同时发现HIV感染者PBMC体外培养最大增殖时间与其培养前外周血基础CD4/CD8比值呈明显正相关(P<0.05)。表型分析发现,培养的PBMC为优先CD8细胞增殖的异质T细胞群,主要由CD4、CD8及CD3CD56细胞组成;部分HIV感染者PBMC培养期间分泌白细胞介素(IL)1α、IL12、肿瘤坏死因子(TNF)α和IL10等细胞因子能力较高;而11/12例HIV感染者PBMC体外培养初期可扩增出大量病毒,但随着培养时间的延长,病毒载量逐渐降低甚至低于检测限。结论体外大量扩增基础CD4/CD8比值较高的HIV感染者外周血PBMC是可行的,扩增的细胞具备较强的Th1细胞免疫反应能力,为进一步开展艾滋病的免疫细胞治疗提供必要的实验数据。