B-1a B cells that link the innate and adaptive immune responses are lacking in the absence of the spleen

Splenectomized individuals are prone to overwhelming infections with encapsulated bacteria and splenectomy of mice increases susceptibility to streptococcal infections, yet the exact mechanism by which the spleen protects against such infections is unknown. Using congenitally asplenic mice as a model, we show that the spleen is essential for the generation of B-1a cells, a B cell population that cooperates with the innate immune system to control early bacterial and viral growth. Splenectomy of wild-type mice further demonstrated that the spleen is also important for the survival of B-1a cells. Transfer experiments demonstrate that lack of these cells, as opposed to the absence of the spleen per se, is associated with an inability to mount a rapid immune response against streptococcal polysaccharides. Thus, absence of the spleen and the associated increased susceptibility to streptococcal infections is correlated with lack of B-1a B cells. These findings reveal a hitherto unknown role of the spleen in generating and maintaining the B-1a B cell pool.     

Reduced expansion rate of abdominal aortic aneurysms in patients with diabetes may be related to aberrant monocyte-matrix interactions

Aims: Diabetes increases the risk of atherothrombosis, but reducesthe risk of abdominal aortic aneurysm (AAA). The reason forthis difference is unknown. We examined the role of diabetesand glycation on AAA expansion and extracellular matrix–monocyteinteractions. Methods and results: We followed 198 patients (20 with diabetes) who had 30–45mm AAAs with yearly aortic ultrasound for 3 years. Diabeteswas independently associated with reduced AAA growth (β= –0.17, P = 0.01; OR for expansion above median 0.18,95% confidence interval 0.06–0.57). In vitro incubationof resting human monocytes with glycated bovine serum albuminor monomeric type I collagen increased matrix metalloproteinase(MMP) secretion. In contrast, exposure of activated monocytesto glycated type I collagen lattices induced a marked reductionin MMP and interleukin-6 secretion. This de-activating effectwas also demonstrated in cross-linked non-glycated collagenlattices, healthy decellularized aortic media, and decellularizedaortic media from diabetes patients with atherosclerosis. Incontrast, decellularized aortic media from patients with atherosclerosis,but no diabetes, induced increased MMP secretion. Conclusion: These findings confirm that the progression of AAA is slowerin patients with diabetes and suggest a mechanism by which theaortic media may be protected from degradation in these individuals.     

Setting the stage for acute-on-chronic kidney injury

Acute-on-chronic kidney disease will be familiar to many nephrologists. Hsu et al. quantify the risk of acute-on-chronic disease across the stages of preexisting chronic kidney disease. Their study demonstrates the valuable insights that large epidemiological studies can bring to the field of acute kidney injury.     

Chronic arsenic exposure and adverse pregnancy outcomes in bangladesh

BACKGROUND: Chronic exposure to arsenic through drinking water has the potential to cause adverse pregnancy outcomes, although the association has not been demonstrated conclusively. This cross-sectional study assessed the association between arsenic in drinking water and spontaneous abortion, stillbirth, and neonatal death. METHODS: In this cross-sectional study, 533 women were interviewed. Information on sociodemographic characteristics, drinking water use, and adverse pregnancy outcomes was obtained through a structured pretested interviewer-administered questionnaire. The respondents reported use of a total of 223 tube wells; for 208 wells, water samples were measured using an ultraviolet/visible spectrophotometry method, whereas 15 were measured by flow-injection hydride generation atomic absorption spectrometry (FIHG-AAS). RESULTS: Excess risks for spontaneous abortion and stillbirth were observed among the participants chronically exposed to higher concentrations of arsenic in drinking water after adjusting for participant's height, history of hypertension and diabetes, and (for neonatal death only) age at first pregnancy. Comparing exposure to arsenic concentration of greater than 50 microg/L with 50 microg/L or less, the odds ratios were 2.5 (95% confidence interval=1.5-4.3) for spontaneous abortion, 2.5 (1.3-4.9) for stillbirth, and 1.8 (0.9-3.6) for neonatal death. CONCLUSIONS: These study findings suggest that chronic arsenic exposure may increase the risk of fetal and infant death.     

骨质疏松性椎体骨折模型的建立

目的:建立大鼠的骨质疏松性椎体骨折模型,探讨骨折愈合程度与X射线、骨结构和力学性能的相互关系,以期能为临床治疗提供科学的指导和理论依据。方法:实验于2005-07/2006-07在解放军兰州军区总医院骨研所完成。实验动物:选择雌性SPF级8个月龄SD大鼠54只。实验分组:采用随机数字法将大鼠分为2组:骨质疏松组和对照组,每组27只。实验干预:骨质疏松组经双背侧手术切除卵巢,对照组行伪手术。术后3个月,所有动物麻醉下,采用L5椎体手术开窗刮除术区内松质骨方法建立人工椎体骨折模型。实验评估:于术后1,2,4,6,8,12周观察两组大鼠腰椎影像学、骨组织切片组织学与受累椎体力学性能。结果:54只SD大鼠全部进入结果分析。①影像学观察:术后两组X射线片示L5椎体有一骨折缺损透光区。对照组在术后6周时原透光区与周围骨质无明显差别,而骨质疏松组原透光区仍清晰可见,于8周时无明显差别。②组织学观察:两组软骨细胞在骨愈合1周时出现,形成软骨岛,但骨质疏松组软骨细胞每高倍视野数量明显少于对照组,另外,软骨细胞改建成成熟骨细胞,骨小梁形成数量,胶原纤维排列与对照组比较有显著性差异。③力学性能:在骨质愈合6～12周,L5椎体的最大载荷、弹性模量、最大应力明显低于同期对照组,差异有显著性意义(P<0.05)。结论:骨质疏松性椎体骨折SD大鼠模型,符合动物模型标准,可用于研究新骨形成与正常骨质结构关系,观察骨质疏松性椎体骨折愈合机制,并证明骨质疏松性松质骨骨折修复过程中,骨折愈合质量降低。     

7-溴乙氧苯四氢巴马汀对离体豚鼠工作心脏的作用

用Tris-丙酮酸钠液灌流离体豚鼠工作心脏,记录左室压的导管从左房灌流管插入,可使心脏有效工作时间达70min。用Tris-丙酮酸钠液加0.5%的氟碳液能使有效工作时间延长至90min。7-溴乙氧苯四氢巴马汀(7-bromoethyoxybenzene tetrahydropalmatine,EBP)及哌唑嗪0.1μmol/L对工作心脏各项指标均无显著影响。甲氧胺1μmol/L,多巴胺1μmol/L对LVP,ABF,T-CO等指标均有明显的药理作用。EBP 10μmol/L能对抗甲氧胺、多巴胺对上述指标的影响。     

Spectrum of ENU-induced mutations in phenotype-driven and gene-driven screens in the mouse

N-ethyl-N-nitrosourea (ENU) mutagenesis in mice has become a standard tool for (i) increasing the pool of mutants in many areas of biology, (ii) identifying novel genes involved in physiological processes and disease, and (iii) in assisting in assigning functions to genes. ENU is assumed to cause random mutations throughout the mouse genome, but this presumption has never been analyzed. This is a crucial point, especially for large-scale mutagenesis, as a bias would reflect a constraint on identifying possible genetic targets. There is a significant body of published data now available from both phenotype-driven and gene-driven ENU mutagenesis screens in the mouse that can be used to reveal the effectiveness and limitations of an ENU mutagenesis approach. Analysis of the published data is presented in this paper. As expected for a randomly acting mutagen, ENU-induced mutations identified in phenotype-driven screens were in genes that had higher coding sequence length and higher exon number than the average for the mouse genome. Unexpectedly, the data showed that ENU-induced mutations were more likely to be found in genes that had a higher G + C content and neighboring base analysis revealed that the identified ENU mutations were more often directly flanked by G or C nucleotides. ENU mutations from phenotype-driven and gene-driven screens were dominantly A:T to T:A transversions or A:T to G:C transitions. Knowledge of the spectrum of mutations that ENU elicits will assist in positional cloning of ENU-induced mutations by allowing prioritization of candidate genes based on some of their inherent features.