Behavioral effects of melanocyte stimulating hormone release-inhibiting factor-1 (MIF-1)

Consideration of the isolation, structure, localization, and behavioral effects of melanocyte stimulating hormone release inhibiting factor (MIF-1) is followed by a review of its opiate antagonistic and clinical effects. Evidence pertaining to various hypotheses offered in explanation of these behavioral effects is examined and evaluated. It is concluded that MIF-1 affects behavior in many instances with possible antagonistic effects as well as clinical possibilities.     

Substance P-immunoreactive processes on 5HT/SP-immunoreactive medullary cells

Two-color immunoperoxidase staining has been used to localize substance P (SP)-immunoreactive processes on neurons in the caudal medulla that exhibited both serotonin (5HT)- and SP-immunoreactivity (5HTI/SPI cells). The punctate SP-immunoreactive processes were present on 5HTI/SPI cells in the raphe nuclei and ventral reticular formation. This close association suggests that activity in bulbospinal 5HT/SP pathways, which can influence sympathetic preganglionic neurons, may be affected by the release of SP in the brainstem.     

Toll-like receptors and antimicrobial peptides expressions of psoriasis: correlation with serum vitamin D level

To evaluate the association of Toll-like receptors (TLRs), antimicrobial peptides (AMPs) and vitamin D receptors (VDRs) in psoriasis, lesional (PP) and perilesional skin (PN) from psoriasis, atopic dermatitis (AD) patients and healthy controls (NN) were studied by immunohistochemistry. Compared with PN, AD and NN skin, dysregulated expression of TLRs, AMPs and VDR was detected in PP skin. Noteworthy, our results showed altered correlation between TLR2 and VDR expression in PP and PN skin. Human beta defensin 2 (HBD2) and cathelicidin (LL-37) expressions in the PP skin were higher in serum vitamin D sufficient (VDS) groups than serum vitamin D deficient (VDD) groups. Negative correlation was found between TLR2 and VDR expression in the PP skin of VDD groups. However, positive correlation was noted in the PP skin of VDS groups. Based on the present results, therapies targeting the activity of TLRs, AMPs and vitamin D, including modulation of the TLR-VDR pathways, might provide new therapeutic approaches to the psoriasis and other inflammatory skin diseases.     

应用MALDI-TOF-MS技术分析HIV感染者血清多肽变化

目的用基质辅助激光解析电离飞行时间质谱 （matrix-assisted laser desorption/ionization ti me offlight mass spectrometry,MALDI-TOF-MS）技术,分析艾滋病病毒（HIV）感染者和健康人血清多肽图谱的变化。方法选取20例HIV感染者、24例健康对照者的血清,经Zipplate C18层析预分离后,运用MALDI-TOF-MS分析检测,获得HIV感染者和健康人血清标本的多肽指纹图谱,并用SPSS 13.0软件对数据进行分析。随后,用质谱串联技术（MS/MS）对两个差异表达显著的多肽峰测定肽序列,在SWISS-PROT数据库进行多肽鉴定。结果在分子量为800~4 000D范围内,共发现500个多肽峰,其中11个多肽峰在HIV感染者组、正常对照组中表达均有显著差异（P〈0.05）,5个差异多肽在HIV感染者组中表达上调（m/z 1 418.67、1 465.67、1 777.82、1 864.82和2 080.23）,6个差异多肽在HIV感染者组中表达下调（m/z 904.71、920.73、1 076.73、1 521.79、1 552.75和2 080.78）;经质谱串联技术对两个表达显著差异的多肽峰测定肽序列,鉴定结果分别是纤维蛋白多肽（Fibrino-peptide）、激肽原（Kininogen processor）。结论HIV感染者和健康人血清标本的多肽指纹图谱有显著差异,通过多肽指纹图谱找到的HIV相关多肽,为今后开发HIV诊断试剂和治疗药物,提供科学依据。     

HLA class II influences humoral autoimmunity in patients with type 2 autoimmune hepatitis

BACKGROUND/AIMS: Type 2 autoimmune hepatitis (AIH) is characterized by the presence of anti-liver kidney microsome (anti-LKM-1) and/or anti-liver cytosol type 1 (anti-LC1) autoantibodies. However, the correlation between these autoantibodies and the genetic background has not been studied. METHODS: Frequencies of HLA class II alleles were compared between the 60 Caucasian children with type 2 AIH and 313 control subjects. The anti-LKM1 antibody reactivity directed against antigenic sites of CYP2D6 was analysed by ELISA. RESULTS: HLA-DQB1 *0201 allele was found to be the primary genetic determinant of susceptibility to type 2 AIH by conferring the highest odd-ratio (OR = 6.4). HLA-DRB1 *03 allele was significantly increased (P < 0.0001) among patients with both anti-LKM1 and anti-LC1 autoantibodies as well as in those with only anti-LC1(+) compared to those with anti-LKM1(+) alone. In contrast, HLA-DRB1 *07 allele was significantly associated (P < 0.0001) with anti-LKM1(+) alone compared to groups with both anti-LKM and anti-LC1 or with LC1+ alone. Children with the DRB1 *07 allele develop anti-LKM1 autoantibodies having a more restricted specificity (2 epitopes) than to those having HLA-DRB1 *03 allele (5 epitopes). CONCLUSIONS: The HLA-DR locus is involved in autoantibody expression, while the DQ locus appears to be a critical determinant for the development of type 2 AIH.     

抗环瓜氨酸肽抗体联合类风湿因子检测在类风湿关节炎诊断中的应用

目的探讨抗环瓜氨酸肽抗体联合类风湿因子检测在类风湿关节炎（RA）诊断中的临床应用价值。方法分别用电化学发光法及免疫散射法同时检测90例（临床已确诊为RA患者48例、其他疾病患者22例及健康对照组20例）血清中的抗环瓜氨酸肽抗体及类风湿因子。结果抗环瓜氨酸肽抗体对RA诊断敏感性为72．92％,特异性为97．61％：类风湿因子对RA诊断的敏感性为85．42％,特异性为71．43％;抗环瓜氨酸肽抗体与类风湿因子联合平行试验对RA诊断的敏感性为96．05％,特异性为69．72％。结论抗瓜氨酸肽抗体与类风湿因子联合检测可提高RA诊断的敏感性且具有较高的特异性．有利于RA的早期诊断。     

抗核抗体和抗环瓜氨酸肽抗体在风湿性疾病中的应用

目的探讨抗核抗体（ANA）和抗环瓜氨酸肽（CCP）抗体在风湿性疾病中的敏感性及相关性。方法收集浏阳市人民医院2010年9月至2013年2月433例已确诊为风湿性疾病患者和60例健康体检人员的血清．采用间接免疫荧光试验（IIFA）检测ANA,判断荧光核型,免疫印迹试验（UA）抗核抗体谱（ANAs）12项检测特异性抗体,胶体金法测定抗CCP抗体,并对结果进行相关分析。结果（1）在433例风湿性疾病患者血清标本中,ANA核型阳性共258例．其中系统性红斑狼疮阳性率为83．03％（137／165）,类风湿关节炎（RA）阳性率为26．85％（40／149）,原发性干燥综合征阳性率为64．15％（34／53）,混合结缔组织病阳性率为[00．00％（20／20）,多肌炎／皮肌炎阳性率为33．33％（8,24）,进行性系统性硬化症阳性率为86．36％（19／22）;健康对照组阳性率为0．00％。（2）抗双链DNA（ds—DNA）抗体、抗史密斯（Sm）抗体、抗核糖体P蛋白抗体（ARPA）、抗组蛋白抗体和核小体抗体阳性标本中均质型所占比例最高：抗尿嘧啶-1低相对分子质量核糖核蛋白（抗U1．nRNP）抗体、抗干燥综合征抗原A（SS—A）抗体、抗SS．B抗体阳性标本中,斑点型所占比例最高;抗硬皮病-70（Sel-70）抗体主要见于均质核仁混合型;抗组氨酰．tRNA合成酶（Jo．1）抗体阳性标本中,胞浆型所占比例最高;抗着丝点B（CENPB）抗体则全为着丝点阳性;（3）在175例IIFA．ANA阴性（IIFA—ANA-）标本中,UA．ANAs阳性（LIA—ANAs-）1例;（4）433例风湿性疾病患者中,抗CCP抗体阳性82例,其中RA组阳性率为51．68％（77／149）,非RA组阳性率为1．76％（5／284）。结论ANAs中抗ds．DNA抗体、抗Jo．1抗体、抗CENPB抗体与ANA的荧光模式和风湿性疾病类型有一定关联：ANA核型以斑点型所占比例最高;IIFA—ANA-者检出LIA．ANAs-的可能性较小;抗CCP抗体对RA的诊断具有较好的灵敏度和特异性,是诊断RA的特异性血清学标志。     

Penetratin analogues acting as antifungal agents

The synthesis, in vitro evaluation, and conformational study of penetratin analogues acting as antifungal agents are reported. Different peptides structurally related with penetratin were evaluated. Analogues of penetratin rich in Arg, Lys and Trp amino acids were tested. In addition, HFRWRQIKIWFQNRRM[O]KWKK-NH₂, a synthetic 20 amino acid peptide was also evaluated. These penetratin analogues displayed antifungal activity against human pathogenic strains including Candida albicans and Cryptococcus neoformans. In contrast, Tat peptide, a well-known cell penetrating peptide, did not show a significant antifungal activity against fungus tested here. We also performed a conformational study by means experimental and theoretical approaches (CD spectroscopic measurements and MD simulations). The electronic structure analysis was carried out from Molecular Electrostatic Potentials (MEP) obtained by using RHF/6-31G ab initio calculations. Our experimental and theoretical results permitted us to identify a topographical template which may provide a guide for the design of new peptides with antifungal effects.     

慢性心力衰竭脂联素和血浆氧化低密度脂蛋白相关性研究

目的探讨慢性心力衰竭(CHF)患者血浆脂联素(APN)和氧化低密度脂蛋白(oxLDL)与心功能的关系。方法选择124例CHF患者,按NYHA心功能分级分为3组(心功能Ⅱ级,Ⅲ级,Ⅳ级组),40例健康体检者为对照组,应用酶联免疫法测定2组血浆APN和oxLDL水平,进行组间统计学比较及各参数之间的相关分析。结果 CHF患者基础血浆APN和oxLDL水平明显高于健康对照组(P<0.01),且随NYHA级别的增加而增高(P<0.01);CHF患者的血浆APN和oxLDL水平经治疗后较治疗前均明显下降(P<0.01);缺血型心肌病心衰和扩张型心肌病心衰两组之间血浆APN和oxLDL水平差异无统计学意义(P<0.01);血浆APN与oxLD两者呈正相关(r=0.627,P<0.01)。结论 CHF患者血浆APN和oxLDL显著增高,并与CHF严重程度存在正相关性;缺血性心肌病心衰与扩张型心肌病心衰两组之间血浆APN与oxLD均升高,且无相关性。     

^99Tc^m标记亲肿瘤三肽的实验研究

目的 进行99Tcm-精氨酸-谷氨酸-丝氨酸（RES）的亲肿瘤实验研究.方法 采用标准Fmoc固相合成法合成RES,在不同的试剂和温度（100 ℃或室温）条件下,以氯化亚锡为还原剂进行RES的99Tcm标记,优化标记条件.进行荷A549肺癌裸鼠99Tcm-RES显像并测定%ID/g,研究99TcmRES在荷瘤裸鼠体内的分布.比较兔炎性反应和肿瘤模型显像结果.结果 （1）酒石酸钠及氢氧化钠为缓冲剂,氯化亚锡为还原剂,100 ℃水浴10 min,RES放化纯最高达到85%;99Tcm-RES性能稳定,室温下放置6 h,放化纯仍达75%.（2）注射后0.5 h,99Tcm-RES多分布于心、肝、肾等血供丰富脏器,2 h血液的放射性（0.36%ID/g）降幅明显,仅相当于0.5 h（2.35%ID/g）的1/7;心、肝、肺的放射性降幅稍慢,但明显快于肿瘤;注射后0.5 h肿瘤放射性摄取为2.32%ID/g,6 h为1.54%ID/g,6 h后仍有超过60%的放射性滞留.99Tcm-RES注射后6 h肿瘤/血、肿瘤/心、肿瘤/肝、肿瘤/肺、肿瘤/脾和肿瘤/骨骼肌放射性比值分别为5.31,1.88,1.57,3.58,4.16和5.92.（3）荷瘤鼠显像发现肿瘤部位明显浓聚99Tcm-RES,而201Tl、99Tcm-MIBI在肿瘤部位未见明显浓聚.（4）兔炎性反应和肿瘤模型显像示肿瘤部位放射性明显浓聚,而炎性反应部位放射性无明显浓聚,注药后6 h肿瘤/炎性反应部位放射性比值为3.12.结论 用放射性组合化学文库筛选出的小分子RES是一种与肿瘤高亲和力的多肽,有望成为一种肿瘤显像剂.