Determination of malondialdehyde-induced DNA damage in human tissues using an immunoslot blot assay

Malondialdehyde (MDA) is a product of lipid peroxidation and prostaglandin biosynthesis. It is mutagenic and carcinogenic and the major adduct formed by reaction with DNA, a highly fluorescent pyrimidopurinone (M1-dG), has been detected in healthy human liver and leukocyte DNA. Analytical methods used so far for the detection of M1- dG have not been applied to a large number of individuals or variety of samples. Often, only a few microg of DNA from human tissues are available for analysis and a very sensitive assay is needed in order to detect background levels of M1-dG in very small amounts of DNA. In this paper, the development of an immunoslot blot (ISB) assay for the measurement of MI-dG in 1 microg of DNA is described. The limit of detection of the assay is 2.5 adducts per 10(8) bases. A series of human samples were analysed and levels of 5.6-9.5 (n = 8) and 3.1-64.3 (n = 42) of M1-dG per 10(8) normal bases were detected in white blood cell and gastric biopsy DNA, respectively. Results on four human samples were compared with those obtained using an HPLC/32P-post- labelling (HPLC/PPL) method previously developed and indicated a high correlation between M1-dG levels measured by the two assays. The advantages of ISB over other assays including HPLC/PPL, such as the possibility of analysing 1 microg DNA/sample and the fact that it is less time-consuming and laborious, means that it can be more easily used for routine analysis of a large number of samples in biomonitoring studies.      

肿瘤治疗存在的问题及中西医结合的研究重点

目前的肿瘤治疗主要存在以下几个问题：(1)肿瘤的过度治疗普遍存在；(2)急功近利而缺乏长远规划；(3)综合治疗缺乏合理的内涵；(4)缺少有效的个体化治疗方案；(5)对中医药的优势认识不足、发挥不够。中西医结合在肿瘤防治中大有可为，应重点围绕以下几个方面开展研究工作：(1)加强中医对恶性肿瘤基础知识的认识和研究；(2)加强中西医结合治疗肿瘤合理化、规范化方案的研究；(3)加强中西医结合治疗恶性肿瘤疗效标准的研究；(4)加强中西医结合防治肿瘤术后复发、转移的研究。     

Reimagining care for young adults living with type 1 diabetes

Young adults living with type 1 diabetes often struggle to achieve what clinicians consider to be optimal levels of metabolic control. Despite the impact that this can have on a young person''s future risk of complications, there are relatively few studies reporting new ways of organizing or delivering care to this cohort. In this article, we explore some of the reasons why young adult diabetes care is challenging, and describe approaches to “re‐imagining” how care might be improved. The work is informed by the ‘Making Care Fit’ collaborative and by a program of research, entitled D1 Now, involving co‐design of a complex person‐centered intervention with young adults.     

严重烧伤患者外周血T淋巴细胞亚群、NK细胞活性及sIL-2R水平的变化

目的观察严重烧伤患者伤后T淋巴细胞亚群、NK细胞活性和sIL2R水平的变化,探讨其免疫功能改变的可能机制。方法测定35例严重烧伤患者伤后T淋巴细胞亚群,NK细胞活性和sIL2R的水平,并与正常对照组进行比较。结果与正常对照组比较,烧伤组:CD3+、CD4+和CD4+/CD8+比值均明显下降(P均<0.01),CD8+明显升高(P<0.05),烧伤组NK细胞活性明显下降(P<0.05),sIL-2R明显升高(P<0.01)。结论严重烧伤患者T淋巴细胞亚群中细胞比例发生了明显改变,NK细胞活性降低sIL-2R水平升高,三者互相影响,共同构成烧伤患者伤后免疫功能紊乱的因素之一。     

A comparison of the adverse reactions associated with isosulfan blue versus methylene blue dye in sentinel lymph node biopsy for breast cancer

BACKGROUND: Sentinel lymph node biopsy (SLNB) is an established means of staging the axilla in patients with breast cancer. Recently, methylene blue dye has been shown to be an efficacious and cost-effective alternative to isosulfan blue. With the increasing popularity of SLNB, the potential complications of isosulfan blue use must be appreciated. METHODS: A literature search for English language articles available on MEDLINE from 1985 to November 2002 using the search terms allergy, allergic reaction, anaphylactic reactions, anaphylaxis, blue dye, breast cancer, isosulfan blue, methylene blue, and sentinel lymph node biopsy identified 24 reports. CONCLUSIONS: The use of isosulfan blue due for SLNB is associated with a significant number of allergic reactions, some of which are life-threatening. Because methylene blue dye has been shown to be equally effective and does not pose a serious risk of serious allergic reactions, it offers an improved technique above isosulfan blue dye for SLNB.     

Translumbar catheter redirection using a tip-deflector technique

A new technique is described for reversing the direction of the catheter tip during translumbar aortography, without the need for partial withdrawal of the catheter from the aortic lumen. The method ensures optimal delivery of contrast medium at the desired level, while avoiding the risk of retroperitoneal bleeding or dislodgement during catheter manipulation.     

Tryptophan 650 of human granulocyte colony-stimulating factor (G-CSF) receptor, implicated in the activation of JAK2, is also required for G- CSF-mediated activation of signaling complexes of the p21ras route

Granulocyte colony-stimulating factor (G-CSF) induces rapid phosphorylation of JAK kinases as well as activation of the p21ras route through interaction with its specific receptor (G-CSF-R). The cytoplasmic membrane-proximal region of G-CSF-R (amino acids 631 to 684) is necessary for proliferation induction and activation of JAK2. In contrast, activation of Shc and Syp, signaling molecules implicated in the p21ras signaling route, depends on the phosphorylation of tyrosine residues located in the membrane-distal region (amino acids 685 to 813) of G-CSF-R. We investigated whether G-CSF-induced activation of signaling complexes of the p21ras route depends on the function of the membrane-proximal cytoplasmic region of G-CSF-R. A G- CSF-R mutant was constructed in which tryptophan 650 was replaced by arginine and expressed in BAF3 cells (BAF/W650R). In contrast to BAF3 cell transfectants expressing wild-type G-CSF-R, BAF/W650-R cells did not proliferate and did not show activation of JAK2, STAT1, or STAT3 in response to G-CSF. Immunoprecipitations with anti-Shc and anti-Grb2 antisera showed that mutant W650R also failed to activate Syp and Shc. These data indicate that the membrane-proximal cytoplasmic domain of G- CSF-R is not only crucial for proliferative signaling and activation of JAK2 and STATs, but is also required for activation of the p21ras route, which occurs via the membrane-distal region of G-CSF-R.     

Effects of interleukin-11 on the proliferation and cell cycle status of myeloid leukemic cells

Interleukin-11 (IL-11) is a pleiotropic cytokine with effects on many different targets. Within the hematopoietic system, the effects of IL- 11 are largely manifest only through combination with other cytokines, including IL-3 and Steel factor (SF). In the present study, we addressed the question of IL-11 responsiveness within the different types of human leukemic cells, as well as the mechanism of action of IL- 11 at the cellular level. Analysis of a panel of samples from different patients with acute myeloblastic leukemia (AML) and myeloid leukemic cell lines indicated that IL-11 alone was ineffective in supporting myeloid leukemic cell growth but frequently enhanced growth supported by IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), or SF. In contrast, three acute pre-B lymphocytic leukemia (pre-B-ALL) and two acute T lymphocytic leukemia (T-ALL) lines failed to respond to IL- 11 alone or when combined with other cytokines. The growth enhancement of IL-11 among the AML patient samples was dose dependent and remarkably constant with half-efficient concentrations in the range of 0.3 to 0.4 ng/mL. The thymidine suicide studies with the patient samples revealed that 40% to 50% of the blast cells were in S-phase when exposed for 16 hours to IL-3 and this level was increased to 70% to 90% in response to either IL-11 or IL-6. Our data suggest that the latter two interleukins act synergistically with the direct mitogenic factor, IL-3, in triggering AML blast-cell proliferation. Detailed analysis with several patient samples further revealed that SF and IL- 11 both enhance IL-3-supported clonogenic growth of AML blasts and the combination of all three growth factors yields optimal growth. In contrast, IL-6 does not further enhance the effect of IL-11. These results indicate that SF and IL-11 enhance IL-3-dependent clonogenic growth through two distinct pathways, whereas IL-6 and IL-11 may trigger the same pathway.