Enhancement by dimethyl myleran of donor type chimerism in murine recipients of bone marrow allografts

A major problem in using murine models for studies of bone marrow allograft rejection in leukemia patients is the narrow margin in which graft rejection can be analyzed. In mice irradiated with greater than 9 Gy total body irradiation (TBI) rejection is minimal, whereas after administration of 8 Gy TBI, which spares a significant number of clonable T cells, a substantial frequency of host stem cells can also be detected. In current murine models, unlike in humans, bone marrow allograft rejection is generally associated with full autologous hematopoietic reconstitution. In the present study, we investigated the effect of the myeloablative drug dimethyl myleran (DMM) on chimerism status following transplantation of T cell-depleted allogenic bone marrow (using C57BL/6 donors and C3H/HeJ recipients, conditioned with 8 Gy TBI). Donor type chimerism 1 to 2 months post-transplant of 1 to 3 x 10(6) bone marrow cells was markedly enhanced by using DMM one day after TBI and prior to transplantation. Conditioning with cyclophosphamide instead of DMM, in combination with 8 Gy TBI, did not enhance engraftment of donor type cells. Artificial reconstitution of T cells, after conditioning with TBI plus DMM, by adding mature thymocytes, or presensitization with irradiated donor type spleen cells 1 week before TBI and DMM, led to strong graft rejection and consequently to severe anemia. The anti-donor responses in these models were proportional to the number of added T cells and to the number of cells used for presensitization, and they could be neutralized by increasing the bone marrow inoculum. These results demonstrate the potential of DMM to facilitate engraftment in unsensitized mice in which the host stem cells may compete with donor type cells; the use of DMM to create models in which mechanisms of immune rejection can be studied without interference due to stem cell competition; and that bone marrow allograft rejection may be overcome by increasing the bone marrow inoculum in these stringent models.     

von Willebrand factor and von Willebrand disease [published erratum appears in Blood 1988 Mar;71(3):830]

Progress has occurred in the past several years in the understanding of the structure and function of von Willebrand factor (vWF). This multimeric glycoprotein exhibits a dual role, that of mediating platelet adhesion and aggregation onto thrombogenic surfaces, and that of functioning as carrier in plasma for the factor VIII procoagulant protein. New insights into the nature of the several functional domains of vWF have led to the identification of the regions of the molecule that interact with factor VIII, heparin, the glycoprotein lb of platelets, and collagen. Alterations of vWF are the cause of von Willebrand disease (vWD), a congenital bleeding disorder. In the majority of patients, the plasma levels of vWF are decreased, but there is no demonstrable structural or functional alteration of the protein. In other patients, however, the structure of vWF is abnormal. This review summarizes the current knowledge on vWF and vWD.     

一氧化氮在神经退行性疾病中的作用:非类固醇性抗炎药的治疗前景(英文)

一氧化氮(nitric oxide, NO)是一类胞内信使。研究表明,神经退行性病人脑组织中催化合成NO的酶的表达水平显著提高,提示NO与神经退行性疾病密切相关。此外,在这些组织中还检测到硝化的蛋白,提示NO在这些组织中具有生物活性。在神经免疫应答中,神经元和胶质细胞(包括小胶质细胞和星形胶质细胞)内都发生了NO水平的改变。很多神经退行性疾病都伴随有神经炎症,抑制神经炎症的信号通路能延迟这些疾病的发展。因此,NO及其释放通路已逐渐成为神经退行性疾病研究领域的热点,对它们的理解能帮助我们找到合适的方案来预防、减缓或者治愈这些疾病。     

Vitamin D Deficiency as a Factor Influencing Asthma Control in Children

Objective

To study the association between asthma control and serum 25OH Vitamin D levels in children with moderate persistent asthma on preventer therapy.

Methods

Children aged 6–18 years, with moderate persistent asthma, on preventer therapy for ≥2 months were included. Control was categorized as good, partial or poor as per GINA guidelines. Serum 25 (OH) Vitamin D levels were measured and their relationship with the level of control was studied.

Results

Out of 50 children enrolled, 22 had well-controlled asthma, and 21 had partially controlled asthma. Vitamin D was deficient in 30 children and insufficient in 18 children. Children with vitamin D deficiency had significantly less wellcontrolled asthma as compared to those with insufficient or sufficient levels of 25 (OH) vitamin D (13.3% vs 88.9 % vs 100%).

Conclusion

Vitamin D deficiency is associated with suboptimal asthma control.

     

Correction: Propensity-matched analysis of patients with intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma and hepatocellular carcinoma undergoing a liver transplant

Rereading the article “Propensity-matched analysis of patients with intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma and hepatocellular carcinoma undergoing a liver transplant” (DOI: 10.5306/wjco.v13.i8.688), published on August 24, we observe, with concern, that figures 3 and 4 are wrong. The authors have attached the correct figures for correction.