蛋白质Z与动脉粥样硬化性脑梗死的相关性

目的 观察蛋白质Z（Protein Z,PZ）在动脉粥样硬化性脑梗死（Atherosclerotic cerebral infarction,ACI）患者急性期内的变化,分析PZ与D-二聚体（DD）、纤维蛋白原（FIB）在ACI患者中变化的相关性及血浆PZ的检测在ACI患者中的诊断价值及临床意义.方法 病例组选择发病在72h之内的ACI患者;对照组来自本院健康体检者.所有受检者均于入院即时及入院第14天抽取静脉血测定PZ和相关血凝因素等资料.另采用头颅CT或MRI测量与症状和体征相对应的最大低密度影面积,以及美国国立卫生研究院卒中量表（NIHSS）进行神经功能缺损评分.结果 ACI患者发病3d内血浆PZ、DD、FIB水平明显高于对照组;入院第14天所测的PZ、DD明显高于入院即时所测水平;在诊断ACI的过程中PZ的曲线下面积（AUC）、灵敏度和特异度均高于其他凝血因素,ACI患者血浆PZ浓度与梗死面积及NIHSS评分无相关性.结论 本研究证实了ACI急性期患者体内存在凝血-纤溶系统异常;PZ是脑梗死的一个的危险因素;通过对ACI急性期患者血浆PZ水平及其他血凝因素的检测,结合临床症状、体征及影像学检查,有助于对ACI的诊断和对病情作出判断.     

The relationship between blood leptin level and bone density is specific to ethnicity and menopausal status

Leptin, the obesity hormone, has been linked to bone mineralization and tumorigenesis. In addition, both bone mineral density (BMD) and postmenopausal breast cancer are associated with obesity, but the interrelationships between obesity, leptin, BMD, and breast cancer are not yet clear. In particular, there is little published research comparing white and black women in terms of these variables. We obtained blood specimens for leptin analysis from a group of 320 breast cancer patients and controls with an ethnic composition of 49% white women and 51% black women. Distal and proximal radial BMD (DBMD and PBMD) were measured by dual-energy X-ray absorptiometry, and age- and ethnicity-specific standardized scores (Z-scores) were calculated for bone density. Blood leptin levels were determined by radioimmunoassay. Blood leptin level was not linked to breast cancer risk. Leptin levels were significantly higher in black women than in white women and were also significantly higher in obese and overweight women than in normal-weight women. Black women weighed more and had a higher body mass index (BMI) than white women. After controlling for BMI, leptin was correlated with DBMD ( r = .17; P < .05) and PBMD ( r = .21; P < .05) in whites, but not in blacks. Leptin was also correlated with both distal and proximal Z-scores in postmenopausal women ( r = .14 and .13; P < .05). Thus leptin may be a predictor for BMD in a population that is prone to have a low BMD, and this relationship is independent of the effect of body weight on leptin levels. Our results suggest that ethnicity and menopausal status should be considered when comparing results from different studies.     

Low protein Z levels, but not the intron F G79A polymorphism, are associated with unexplained pregnancy loss

Introduction

The present case-control study was designed in order to investigate the association between plasma protein Z (PZ) levels, the intron F G79A polymorphism and unexplained pregnancy loss.

Materials and Methods

51 women with at least two consecutive or three non-consecutive fetal losses between the 8th and 12th week of gestation and 47 apparently healthy parous women of reproductive age with no history of pregnancy loss (controls) were enrolled. Allele frequencies of the PZ intron F G79A polymorphism and PZ levels were measured.

Results

PZ levels (mg/L) were significantly lower in cases (mean±S.D. 1.28 ± 0.56) than controls (1.97 ± 0.76, p < 0.001) and in carriers of the A allele (1.46 ± 0.62), compared to GG homozygous subjects (1.72 ± 0.81, p = 0.044). A higher proportion of cases (41.2%) were PZ-deficient (< 1 mg/L), compared to controls (10.6%, p = 0.001). No significant difference in the frequency of at least one A allele carriers was observed between cases (39.2%) and controls (40.4%).

Conclusion(s)

It is possible that low PZ levels are a novel risk factor for unexplained recurrent miscarriage or fetal death. The presence of the F 79A allele is associated with significantly lower PZ levels, but, in the present study, was unrelated to unexplained early pregnancy loss.     

妊娠高血压孕妇血清PZ和hsCRP含量分析

目的研究妊娠高血压孕妇血清蛋白Z(PZ)和超敏C反应蛋白(hsCRP)含量变化及临床意义。方法分别对妊娠早期、中期、晚期、分娩期的妊娠高血压孕妇及同期正常孕妇(对照)进行血清PZ和hsCRP检测,分析不同妊娠期、不同血压下各组别PZ和hsCRP的差异及其相关性。结果不同妊娠期孕妇血清PZ和hsCRP含量与对照组比较差异有统计学意义(P<0.05或P<0.01);轻、中、重度高血压孕妇的血清PZ含量分别为(1.62±0.41),(1.38±0.32),(1.16±0.26)mg/L,且两两比较差异有统计学意义(P<0.01),血清hsCRP含量分别为(3.69±0.33),(3.90±0.37),(4.16±0.41)mg/L,两两比较差异亦有统计学意义(P<0.05或P<0.01);不同妊娠期孕妇血清PZ和hsCRP含量呈负相关(r=-0.795,P<0.01),不同程度血压孕妇血清PZ和hsCRP含量呈负相关(r=-0.799,P<0.01)。结论血清PZ含量降低和hsCRP含量升高可导致孕妇血压升高,同时血清PZ含量与hsCRP含量呈负相关,检测孕妇血清PZ与hsCRP对临床治疗和预防妊娠高血压有一定意义。     

CYP1B1 and hormone-induced cancer

Cancers in hormone-responsive tissues (e.g., breast, ovary, endometrium, prostate) occur at high incidence rates worldwide. However, their genetic basis remains poorly understood. Studies to date suggest that endogenous/exogenous oestrogen and environmental carcinogens may play a role in development and/or progression of hormone-induced cancers via oxidative oestrogen metabolism. Cytochrome P450 1B1 is a key enzyme in its oestrogen metabolism pathway, giving rise to hydroxylation and conjugation. Although CYP1B1 is expressed in many cancers, particularly high levels of expression are observed in oestrogen-mediated disease. CYP1B1 is more readily found in tumour tissue compared to normal. Given the role of CYP1B1 in pro-carcinogen and oestrogen metabolism, polymorphisms in CYP1B1 could result in modifications in its enzyme activity and subsequently lead to hormone-mediated carcinogenesis. CYP1B1 may also be involved in progression of the disease by altering the tissue response to hormones and clinical response to chemotherapy. The exact mechanism behind these events is complex and unclear. Only a few functional single nucleotide polymorphisms of CYP1B1 are known to result in amino acid substitutions and have been extensively investigated. Studies examining the contribution of different CYP1B1 alleles to hormone-mediated cancer risks are inconsistent. The main focus of this review is to appraise the available studies linking the pathogenesis of the hormone-induced cancers to various CYP1B1 polymorphisms. Additionally, we explore the role of a neuronal protein, γ-synuclein, in CYP1B1-mediated pathogenesis.