Development and results of the Spanish registry of patients with alpha-1-antitrypsin deficiency

The Spanish registry of alpha-1 antitrypsin deficiency was founded in 1993 and became a member of the International Registry (AIR) in 1999. We describe the updating process following its incorporation into AIR and compare the data collected in the first period (1993–1999) and the second period (1999–2005), during which time patients were included exclusively by internet.The registry included 301 patients during period 1, 69% males and 46% had a history of smoking. Their mean age was 46 years (SD = 13) and 284 (94%) had the ZZ phenotype, 49% received augmentation therapy. During period 2, 161 new cases were included, 63% of whom were males with a mean age of 44 years (SD = 16). A total of 126 (78%) had the ZZ phenotype. Only 12% received augmentation therapy. A total of 462 different patients were included in both periods. Significant differences were observed in the number of cases with the SZ phenotype and the severity of FEV₁ impairment between the two periods.Implementation of an internet-based collection of data did not result in a lower rate of reporting to the registry. However, data from a significant number of patient included in period 1 could not be actualized in the new data base.     

Prevalence of autoimmune diseases in islet transplant candidates with severe hypoglycaemia and glycaemic lability: previously undiagnosed coeliac and autoimmune thyroid disease is identified by screening.

AIMS: Autoimmune diseases such as Addison's or coeliac disease can contribute to hypoglycaemia or malabsorption and are more common in Type 1 diabetes (T1DM). This brief report describes the prevalence of known and newly detected autoimmune disease in clinical islet transplant candidates with longstanding T1DM and severe hypoglycaemia and/or glycaemic lability who are routinely screened for coexisting autoimmune disease. METHODS: One hundred and twenty-four C-peptide negative T1DM subjects [77 (62%) female, mean age 44 +/- 9 years, diabetes duration 28 +/- 11 years, body mass index 24.9 +/- 3.5 kg/m(2)] with indications for clinical islet transplantation at the University of Alberta were screened for autoimmune disease by history and measurement of anti-transglutaminase antibodies (positive > 10 U/ml), 09.00 h cortisol (followed by adrenocorticotrophic hormone-stimulation if < 495 nmol/l) and thyroid-stimulating hormone to determine the prevalence of coeliac disease, Addison's disease and autoimmune thyroid disease, respectively. RESULTS: Forty per cent of subjects had one or more coexisting autoimmune disease. The prevalence of autoimmune disease was 35%, coeliac disease 8% and Addison's disease 1.6%. In 11 individuals (9%), one or more autoimmune disease were newly detected (seven coeliac disease and five thyroid disease). Seven of 10 cases of coeliac disease were newly detected. A gluten-free diet in individuals with newly diagnosed coeliac disease reduced gastrointestinal symptoms, but indications for clinical islet cell transplantation persisted. CONCLUSIONS: Coexisting autoimmune disease is common in candidates for clinical islet cell transplantation. Screening in this group identified a substantial number of previously unrecognized cases. Clinicians should consider the presence of autoimmune disease even in the absence of classical symptoms.     

胃良性和恶性病变组织中β-半乳糖凝集素3和接骨木凝集素的表达及其临床病理意义

Objective To study the expressive levels of galectin-3(gal-3) and sambucus nigra agglutinin (SNA) and their clinicopathological significance in the benign and malignant lesions of stomach. Methods EnVisonTM immunohistochemistry for assaying gal-3 expressive level and ABC cytochemistry for determining SNA expressive level were used in conventional paraffin-embedded sections from specimens of gastric cancer(n=49), peritumoral tissues(n=20), metastastic foci of lymph nodes(n=36), and different types of benign lesions(n=80). Results The positive rates of gal-3 and SNA were significantly higher in gastric cancer tissues than those in peritumoral tissues and different types of benign lesions (P<0.05, P<0.01). The positive cases of gal-3 and/or SNA in peritumoral tissues and benign lesions showed mild- to severe-atypical hyperplasia of mucous epithelial cells. No difference was found between the primary foci and metastatic foci in gal-3 and SNA expressions (P>0.05). The positive rates of gal-3 and SNA were significantly lower in histologic grade Ⅱ, infitrating depth T1,T2 and no-metastasis of regional lymph node than those in histologic grade Ⅲ, Ⅳ, infitrating depth T3,T4 and metastasis of lymph node in gastric cancer(P<0.05). The positive rates of gal-3 and SNA were higher in lymphnede metastatic site N1 and no-metastasis of distant organs than those in lymphnede metastatic site N2, N3 and metastasis of distant organs, but no significant difference was found (P>0.05). The consistence was found between the expression of gal-3 and SNA in gastric cancer tissues (χ2=6.59,P<0.05). Conclusions The expressive levels of gal-3 and SNA may be important molecular markers of lectins for reflecting the carcinogenesis, progression and biological behaviors in gastric cancer.     

保罗样激酶基因沉默体外抑制胶质瘤细胞侵袭与生长

目的观察保罗样激酶1基因(plk1)沉默对胶质瘤细胞株-H4体外生长的抑制作用,探讨plk1基因作为胶质瘤治疗靶点的可行性。方法化学合成小片断干扰RNA(siRNA)抑制plk1基因的表达,Western blot检测plk1蛋白质的表达变化,流式细胞仪检测H4细胞周期分布及凋亡程度的变化,体外侵袭实验检测H4细胞侵袭能力的变化,MTT法检测H4细胞增殖速度的变化。结果经siRNA作用48h后,plk1蛋白质水平明显降低;较多的H4细胞聚集于G2/M期附近(P<0.05);细胞凋亡明显上升(P<0.05);细胞体外侵袭能力下降(P<0.05);增殖速度明显缓于对照组(P< 0.05)。结论靶向plk1的siRNA可在体外抑制胶质瘤细胞H4的侵袭与增殖,plk1有可能成为新的潜在胶质瘤治疗靶点。     

小肠吸收胆固醇的分子生物学研究进展

胆固醇通过分布于十二指肠和近段空肠黏膜上皮细胞刷状缘膜的Niemann—Pick C1样蛋白1摄取，ATP结合盒G5、G8抑制小肠对胆固醇的摄取过程。进入上皮细胞的胆固醇大多数被乙酰辅酶A，胆固醇转乙酰基酶2酯化，随后通过组装形成乳糜微粒，经淋巴管进入血循环；另一部分胆固醇则以未酯化形式直接进入血循环形成高密度脂蛋白颗粒。这些过程受核受体——肝脏X受体的调控。年龄、性别、黏膜屏障和小肠传输速度也影响胆固醇的吸收。     

爆炸伤创面IL-1、IL-6、TNF-α、CRP的测定

[目的]检测兔肢体爆炸伤创面组织IL-1、IL-6、TNF-α和CRP含量。[方法]新西兰大白兔24只,随机分为炸伤后即刻取材组（A组,n=12）和炸后1h取材组（B组,n=12）;0.9g铜壳单质猛黑索金炸药（RDX）以海绵间隔5cm,绑于左下肢股部中段前外侧,电引爆,分别取爆炸中心区（Ⅰ区）、爆炸边缘区（Ⅱ区）、爆震区（Ⅲ区）的肌肉组织,测IL-1、IL-6、TNF-α、CRP的含量并取对侧肢体肌肉组织做对照研究。[结果]炸伤后两组各区标本IL-1、IL-6、TNF-α、CRP含量均比正常组织高,差异显著（P〈0.05）,且从Ⅰ区、Ⅱ区到Ⅲ区,含量依次降低,差异显著（P〈0.05）：A组：Ⅱ区与Ⅲ区的IL-1含量差别有显著意义（P〈0.05）。Ⅰ区与Ⅲ区、Ⅱ区与Ⅲ区的IL-6含量差别有极显著意义（P〈0.01）。Ⅰ区与Ⅲ区的TNF-α、CRP含量差别有极显著意义（P〈0.01）,Ⅰ区与Ⅱ区、Ⅱ区与Ⅲ区的含量差别有显著意义（P〈0.05）。其余各区的含量无统计学差异（P〉0.05）;B组：Ⅱ区与Ⅲ区的Ⅱ-1、IL-6、TNF-α含量差别有显著意义（P〈0.05）。Ⅰ区与Ⅲ区、Ⅰ区与Ⅱ区、Ⅱ区与Ⅲ区的CRP含量差别有显著意义（P〈0.05）。其余各区的含量无统计学差异（P〉0.05）。A、B两组比较,炸后组织中上述因子表达虽有增强,但差异无显著意义（P〉0.05）。[结论]肢体爆炸伤1h内,创面组织中IL-1、IL-6、TNF-α、CRP表达增强,不同区域间表达有差异。     

p27kip1在宫颈癌组织中的表达及意义

目的 研究p27^kip1在宫颈癌组织中的表达并探讨其在宫颈癌发生发展过程中的变化及意义。方法 采用免疫组化SP法对57例浸润性宫颈癌(IC)、11例宫颈原位癌(CLS)、18例宫颈上皮重度不典型增生(SD)和15例正常宫颈组织(NE)进行了细胞周期蛋白依赖性激酶抑制剂(CDKI）p27^kip1的检测。结果 15例正常宫颈上皮中p27^kip1蛋白全部高表达，而在SD和CLS以及浸润性宫颈癌中，其蛋白表达水平随病变的发展呈现了有意义的下降。在宫颈癌进展期，p27^kip1表达与宫颈癌的临床分期、组织分级、淋巴结转移呈显著负相关，单因素生存分析显示p27^kip1蛋白高表达组生存率明显优于低表达组。结论 p27^kip1蛋白表达的下降参与了宫颈癌的发生发展。其蛋白水平检测是宫颈癌早期诊断及判定预后的一个有价值的指标。     

Body composition in young female adults with Type 1 diabetes mellitus. A prospective case-control study.

AIMS: Overweight is common during late puberty in female patients with Type 1 diabetes. The aim of this study was to examine the change in body composition from late puberty to early adulthood in such female patients in comparison with age-matched control subjects. METHODS: Eighteen females with Type 1 diabetes and 19 healthy female control subjects were recruited for a case-control study at the age of 16-19 years (baseline). Six years later, 16 of the diabetic females and 17 of the control subjects were re-examined (follow-up). Body composition was assessed by dual energy X-ray absorptiometry. RESULTS: Body mass index (BMI) and fat mass index (total fat mass/height2) were significantly higher at baseline in the diabetic patients than in the control subjects (26.4 +/- 2.6 vs. 23.9 +/- 3.7 kg/m2, P < 0.05, and 10.0 +/- 2.4 vs. 8.0 +/- 2.8 kg/m2, P = 0.04, respectively). At follow-up, these parameters still tended to be higher in the diabetic group (27.8 +/- 4.9 vs. 24.6 +/- 5.7 kg/m2, P = 0.09, and 11.8 +/- 5.6 vs. 8.7 +/- 4.9 kg/m2, P = 0.05, respectively). BMI at baseline was strongly correlated to BMI at follow-up in both diabetic patients (r = 0.60; P < 0.05) and control subjects (r = 0.83; P < 0.01). CONCLUSIONS: Increased fat mass in pubertal girls with Type 1 diabetes seems to persist in young adulthood. This study emphasizes the need for new strategies to prevent the development of overweight during puberty in diabetic girls.     

氯沙坦通过下调单核细胞趋化蛋白1受体表达抑制单核细胞活化

目的探讨血管紧张素Ⅱ对单核细胞趋化蛋白1受体CCR2表达的影响及氯沙坦的干预作用。方法人单核细胞株与血管紧张素Ⅱ(10-7mol/L)孵育,加或不加氯沙坦(10-7、10-6和10-5mol/L),检测上清液中单核细胞趋化蛋白1水平、单核和内皮细胞粘附情况以及CCR2mRNA的表达。结果与对照组比较,血管紧张素Ⅱ明显增加单核细胞培养上清液中单核细胞趋化蛋白1水平(26.46±3.58ng/L比10.56±2.34ng/L,P<0.01),增加单核内皮细胞间粘附(596±27比268±16,P<0.01)。血管紧张素Ⅱ刺激细胞后明显上调CCR2mRNA表达,氯沙坦能显著抑制血管紧张素Ⅱ的作用,降低单核细胞趋化蛋白1的水平,减少单核内皮细胞间粘附,下调CCR2 mRNA表达。结论氯沙坦通过下调单核细胞趋化蛋白1受体CCR2基因表达抑制单核细胞活化。