Monocyte chemotactic protein-3 (MCP3) interacts with multiple leukocyte receptors: binding and signaling of MCP3 through shared as well as unique receptors on monocytes and neutrophils

The diversity of monocyte chemotactic protein (MCP)3 target cell types, as well as the capacity of MCP3 to desensitize leukocyte responses to other CC chemokines, suggested that MCP3 may interact with multiple CC chemokine receptors. The purpose of this study is to establish how MCP3 binds and activates monocytes and neutrophils. We show that human monocytes exhibit high-affinity binding for ¹²⁵I-MCP3 with an estimated Kd of 1–3 nM and about 10000 binding sites/cell. The binding of ¹²⁵I-MCP3 to monocytes was progressively less well competed by CC chemokines macrophage inflammatory protein (MIP)lα (Kd = 5–10 nM), RANTES (Kd = 5–10 nM), MCP1 (monocyte chemoattractant and activating factor, or MCAF) (Kd = 60 nM) and MIP1β (Kd > 100 nM). On the other hand, unlabeled MCP3 displaced the binding of radiolabeled MIP1α, RANTES, MCP1 and MIP1β as effectively as the isologous CC chemokines. In agreement with the binding data, pretreatment of monocytes with MCP3 completely desensitized the calcium flux in response to MIP1α and RANTES. However, MIP1α and RANTES failed to desensitize the response of monocytes to MCP3. MCP3 and MCP1 partially desensitized each other's effects on monocytes. These binding and cross-desensitization results suggest that MCP3 binds and signals through other binding sites in addition to those shared with MIP1α, RANTES and MCP1. The unidirectional competition for MIP1β binding and signaling by MCP3 suggests the existence of an as-yet unidentified site for MCP3 shared with MIP1β. The existence of another unique binding site(s) for MCP3 was further shown by the failure of any of the other CC chemokines to compete effectively for MCP3 binding on neutrophils. MCP3 in our study was also the only human CC chemokine that consistently chemoattracted neutrophils. These results suggest that MCP3 is a ligand that can bind and activate a broad range of target cells through receptors shared by other CC chemokines as well as its own receptor.     

Topographical study of the neurons containing hpGRF immunoreactivity in monkey hypothalamus

Hypothalamic neurons producing growth hormone-releasing factor (GRF) have been characterized by immunohistochemistry in monkey hypothalamus, using an antiserum raised against hpGRF1-40, a peptide with GRF activity isolated from a human pancreatic tumor. Cell bodies with hpGRF immunoreactivity were found in arcuate and ventromedial nuclei. From these neurons, bundles of fibers innervate median eminence and appear to terminate in contact with portal vessels. In addition to median eminence, hpGRF immunoreactive fibers were found mostly in the anterior hypothalamus and the arcuate and ventromedial nuclei where they give perineuronal endings. These results correlate with earlier physiological data on hypothalamic control of growth hormone secretion and suggest that GRF is also involved in interneuronal relationships related or unrelated to neurohumoral control of pituitary secretions.     

吗氯贝胺与米帕明治疗抑郁症多中心双盲对照试验

目的 :以经典抗抑郁药物米帕明为阳性对照药采用随机双盲双模拟方法对吗氯贝胺和米帕明治疗抑郁症的疗效和安全性进行研究。方法 :共纳入病人 2 0 0例 ,分别口服吗氯贝胺 3 0 0 -60 0mg d或米帕明75 -2 5 0mg d。结果 :两组病人Hamilton抑郁量表 (HAMD)以及Hamilton焦虑量表 (HAMA)总分在治疗结束时均显著下降 (P <0 0 0 1)。两组之间疗效无显著差异 (p >0 0 5 )。治疗结束时HAMD减分率分别为吗氯贝胺组 0 74± 0 2 4,米帕明组 0 74± 0 2 4(P >0 0 5 ) ;有效率吗氯贝胺组 79 4% ,米帕明组 85 4% (P >0 0 5 )。吗氯贝胺组有 10种不良反应发生频率显著低于米帕明组 ,主要是抗胆碱能、中枢神经系统及心血管系统不良反应。吗氯贝胺的疗效指数也显著高于米帕明组。结论 :吗氯贝胺是一种安全有效的抗抑郁药物     

Functional evidence of decreased tumorigenicity associated with monochromosome transfer of chromosome 14 in esophageal cancer and the mapping of tumor-suppressive regions to 14q32

Despite the abundant evidence of high allelic loss of chromosome arm 14q in human cancers, tumor-suppressor genes mapped to this chromosome have yet to be identified. To narrow the search for candidate genes, we performed monochromosome transfer of chromosome 14 into an esophageal carcinoma cell line, SLMT-1 S1. Statistically significant suppression of the tumorigenic potential of microcell hybrids containing the transferred chromosome 14 provided functional evidence that tumor-suppressive regions of chromosome 14 are essential for esophageal cancer. Tumor segregants emerging in nude mice during the tumorigenicity assay were analyzed by detailed PCR-microsatellite typing to identify critical nonrandomly eliminated regions (CRs). A 680-kb CR mapped to 14q32.13 and an approximately 2.2-Mb CR mapped to 14q32.33 were delineated. Dual-color BAC FISH analysis of microcell hybrids and tumor segregants verified the selective loss of the 14q32.13 region. In contrast, similar transfers of an intact chromosome 11 into SLMT-1 S1 did not significantly suppress tumor formation. These functional complementation studies showing the correlation of tumorigenic potential with critical regions of chromosome 14 validated the importance of the 14q32 region in tumor suppression in esophageal cancer. The present study also paved the path for further identification of novel tumor-suppressor genes that are relevant to the molecular pathogenesis of esophageal cancer.     

Mitochondrial DNA and Y-Chromosome Variation in the Caucasus

We have analyzed mtDNA HVI sequences and Y chromosome haplogroups based on 11 binary markers in 371 individuals, from 11 populations in the Caucasus and the neighbouring countries of Turkey and Iran. Y chromosome haplogroup diversity in the Caucasus was almost as high as in Central Asia and the Near East, and significantly higher than in Europe. More than 27% of the variance in Y‐haplogroups can be attributed to differences between populations, whereas mtDNA showed much lower heterogeneity between populations (less then 5%), suggesting a strong influence of patrilocal social structure. Several groups from the highland region of the Caucasus exhibited low diversity and high differentiation for either or both genetic systems, reflecting enhanced genetic drift in these small, isolated populations. Overall, the Caucasus groups showed greater similarity with West Asian than with European groups for both genetic systems, although this similarity was much more pronounced for the Y chromosome than for mtDNA, suggesting that male‐mediated migrations from West Asia have influenced the genetic structure of Caucasus populations.     

HLA and hypocretin studies in Korean patients with narcolepsy

STUDY OBJECTIVES: Very few studies have evaluated narcolepsy in Asian countries, outside of Japan. Our goal was to study narcolepsy at the genetic, clinical and pathophysiological level in Korea. DESIGN: Prospective study of consecutive patients and age matched controls. Clinical data ascertained from the Stanford Sleep Inventory, Polysomnography and MSLT data, as well as clinical notes. High resolution DRB1 and DQB1 typing in all subjects and studies of CSF hypocretin-1 was also evaluated in a subset of patients. PARTICIPANTS AND SETTING: 20 patients diagnosed at St. Vincent and Korea University Hospitals (Seoul, Korea). 21 Korean control subjects. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: For narcoleptic subjects, mean age was 28.2 years old and 45% were female. Mean BMI was 23.9+/-3.4 kg/m2, a significantly higher value than that expected in an age- and sex-matched sample (p<0.01). All patients had sleepiness and cataplexy while the prevalence of other symptoms ranged from 60-75%. All but 2 subjects were HLA-DR15 (DR2), DQB1*0602 positive (90%). This high DQB1*0602 percentage compared with 24% DQB1*0602 positivity in 21 control Koreans. Protective effects were observed for the DQB1*0601 and DRB1*0406 alleles, Hypocretin (orexin) CSF studies were also performed in 6 cataplectic subjects, all of which had undetectable CSF hypocretin levels. Two of these subjects had started narcolepsy less than 1 year before analysis yet had undetectable hypocretin levels. CONCLUSION: These results illustrate the similarity of narcolepsy-cataplexy in Korea in comparisons with other more studied populations. We also identified a new potential HLA protective subtype, HLA-DRB1*0406.     

PCOS患者AMH水平与性激素及胰岛素抵抗的相关性研究

目的 探讨多囊卵巢综合征(PCOS)患者血清抗苗勒管激素(AMH)水平与性激素及胰岛素抵抗(IR)的相关性.方法 选取2019年1月至12月在西安交通大学第一附属医院妇科内分泌门诊及西北工业大学医院妇科确诊的PCOS患者109例,测定患者血清AM H、性激素水平,应用稳态模型评估胰岛素抵抗指数(HOMA-IR),分析PCOS患者不同AM H水平的性激素及IR值的差异,以及性激素、IR对AM H的影响.结果 对PCOS患者,根据血清AM H检测值按百分位(<25％,25％ ～75％,>75％)进行分层,随着AMH百分位逐渐升高,体质量指数(BMI)、HOMA-IR值均降低(F值分别为3.354、3.712,P<0.05),同时黄体生成素(LH)、睾酮(T)值均升高(F值分别为3.355、3.317,P<0.05).相关性分析显示,血清AMH水平与BMI、HOMA-IR均呈显著负相关(r分别为-0.228、-0.214,P<0.05),与L H、T均呈显著正相关(r分别为0.344、0.327,P<0.01).进一步多元回归分析显示,在控制BMI后,LH及T对AMH存在显著正向影响(β=0.258,P<0.05;β=0.291,P<0.01).结论 PCOS患者血清AMH水平与LH、T均呈正相关,其与HOMA-IR的负相关关系可以由BMI解释.     

重点高中生的心理状态与高考成绩的相关性研究

目的;了解重点高中学生的心理状态与高考成绩之间的关系。方法：以398例应届生为对象,应用16PF人格测验,气质测量工具（STI,TTI）及焦虑自评量表（SAS）,对考生进行测试分析,结果：文理科学生的16PF的人格特质有明显的差别,判别分析和多因素回归分析显示16PF人格特质中的Q1因素（实验性F＝8．76,P＜0．01）,Q2因素（独立性F＝8．23,P＜0．01）,与高考成绩呈正相关,与M因素（幻想性F＝4．88,P＜0．01）,呈负相关;气质中的神经过程灵活性（F＝8．15,P＜0．01）和时间特质中的灵活性（F＝12．36,P＜0．01）与高才成绩呈正相关。结论：高考生的实验性,独立性高分及幻想性低分的个性特质和气质上的灵活性有助于高考成绩的发挥,学生文理科分班宜参考学生人格特质这一特点,。