慢粒白血病abl癌基因表达的研究

选择分别位于ｂｃｒ／ａｂｌ嵌合基因的Ｍｂｃｒｌ第二外显子和ａｂｌ的第二外显子上的两条引物，对１８例慢粒白血病及２例急淋白血病标本进行逆转录ＰＣＲ（ＲＴ－ＰＣＲ）检测。结果：在１８例包括ｐｈ（＋）和ｐｈ（－）不同病期的慢粒白血病患者血中均检出ｂｃｒ／ａｂｌ嵌合基因的表达，其中１４例为Ｋ－２８型表达，１例为Ｌ－６型表达，３例为Ｋ－２８型，Ｌ－６型同时表达；２例急淋白血病标本中１例为Ｋ－２８型表达。研究结果表明，１．ｂｃｒ／ａｂｌ嵌合基因是慢粒白血病的一个重要分子生物学特征；２．ｐｈ（＋）和ｐｈ（－）慢粒白血病的分子生物学基础相同，即均有ｂｃｒ／ａｂｌ嵌合基因；３．至少部分急淋白血病与慢粒白血病有相同的分子生物学基础；４．ｂｃｒ的断裂点位置可能有一定的临床意义，但有待进一步研究；５．同时表达Ｌ－６型和Ｋ－２８型的情况多见于急变区，此现象提示体内可能同时有两类不同嵌合的白血病细胞或白血病急变期ｂｃｒ出现新的重排。     

A cation binding motif stabilizes the compound I radical of cytochrome c peroxidase.

Cytochrome c peroxidase reacts with peroxide to form compound I, which contains an oxyferryl heme and an indolyl radical at Trp-191. The indolyl free radical has a half-life of several hours at room temperature, and this remarkable stability is essential for the catalytic function of cytochrome c peroxidase. To probe the protein environment that stabilizes the compound I radical, we used site-directed mutagenesis to replace Trp-191 with Gly or Gln. Crystal structures of these mutants revealed a monovalent cation binding site in the cavity formerly occupied by the side chain of Trp-191. Comparison of this site with those found in other known cation binding enzymes shows that the Trp-191 side chain resides in a consensus K+ binding site. Electrostatic potential calculations indicate that the cation binding site is created by partial negative charges at the backbone carbonyl oxygen atoms of residues 175 and 177, the carboxyl end of a long alpha-helix (residues 165-175), the heme propionates, and the carboxylate side chain of Asp-235. These features create a negative potential that envelops the side chain of Trp-191; the calculated free energy change for cation binding in this site is -27 kcal/mol (1 cal = 4.184J). This is more than sufficient to account for the stability of the Trp-191 radical, which our estimates suggest is stabilized by 7.8 kcal/mol relative to a Trp radical in solution.     

Subtypes of alpha 1-adrenoceptors in rat blood vessels

Two alpha 1-adrenoceptor subtypes (alpha 1A and alpha 1B) have been distinguished by competitive antagonists and the alkylating agent chloroethylclonidine. The chloroethylclonidine-insensitive subtype (alpha 1A) has been suggested to selectively activate Ca2+ influx through dihydropyridine-sensitive channels in smooth muscle. We compared the effects of chloroethylclonidine and nifedipine on contractile responses to norepinephrine (NE) in rat blood vessels. Pretreatment with chloroethylclonidine caused a large shift to the right and decrease in maximum for NE-induced contractions of rat aorta, however, nifedipine had no effect in this tissue. Chloroethylclonidine had no effect on NE-induced contractions of rat renal arteries, which were almost completely abolished by nifedipine. Both chloroethylclonidine and nifedipine partially attenuated NE-induced contractions in rat mesenteric artery and portal vein. Addition of nifedipine abolished residual contractions remaining after chloroethylclonidine pretreatment in all four types of vessels. The pA2 for the competitive antagonist WB 4101 was highest in renal artery and lowest in aorta. These results suggest that the sensitivity of rat blood vessels to chloroethylclonidine is inversely related to their sensitivity to nifedipine, and support the existence of two alpha 1-adrenoceptor subtypes in rat blood vessels. Rat aorta appears to contain primarily alpha 1B receptors, renal artery primarily alpha 1A, and mesenteric artery and portal vein mixtures alpha 1A of and alpha 1B.     

鼻内法鼻泪管阻塞切除术

本文介绍了鼻内法鼻泪管逆行切除术的切除器制备、应用器械、手术方法及术后处理。并应用本法治疗慢性泪囊炎１０６例１１３眼，术后随访１￣５年，痊愈９３．８％，无效６．２％。     

Financial Implications of Pancreas Transplant Complications: A Business Case for Quality Improvement

We quantified the financial implications of surgical complications following pancreas transplantation. We reviewed medical and financial records of 49 pancreas transplant recipients at the University of Michigan Health System (UMHS) between 1/6/2002 and 11/22/2004. The association of donor, transplant recipient and financial variables was assessed. The median costs to UMHS of procedures and follow-up were $92,917 for recipients without surgical complications versus $108,431 when a surgical complication occurred, a difference of $15,514 (p = 0.03). Median reimbursement by the payer was $17,363 higher in patients with a surgical complication (p = 0.001). Similar trends (higher insurer costs) were noted when stratifying by payer (public and private) and specific procedure (SPK and PAK). All parties (patient, physician, payer and medical center) should benefit from quality improvement, with payers having a financial interest in pancreas transplant surgical quality initiatives.     

Enhanced expression of adenovirus-mediated sodium iodide symporter gene in MCF-7 breast cancer cells with retinoic acid treatment.

Increased expression of the sodium iodide symporter (NIS) is required for effective radioiodine treatment and reporter gene imaging of breast cancer. We investigated the effect of retinoic acid on adenovirus-mediated expression of the human NIS gene in the MCF-7 breast cancer cell line. METHODS: The MCF-7 cell line was infected with recombinant adenovirus carrying the human NIS gene (Rad-NIS). Levels of NIS messenger RNA (mRNA) and protein expression and radioiodine ((125)I) uptake were measured to evaluate adenovirus-mediated NIS gene expression in wild-type and Rad-NIS-infected MCF-7 cells after treatment with all-trans-retinoic acid (ATRA; 10(-8)-10(-6) mol/L). RESULTS: The transduction efficiency of adenovirus in MCF-7 cells at a multiplicity of infection (MOI) of 50 was >60%. After incubation with 10(-6) mol/L ATRA, the mRNA level in Rad-NIS-infected MCF-7 cells increased to 118.5 times that of wild-type MCF-7 cells, whereas the mRNA level in wild-type MCF-7 cells showed only a 2.1-fold increase. Western blot, immunocytochemical staining, and flow cytometry analyses showed that NIS protein expression in MCF-7 cells infected with Rad-NIS increased after ATRA treatment. With ATRA treatment, the amount of (125)I uptake increased in a dose-dependent manner (P < 0.001). The (125)I uptake in wild-type MCF-7 cells increased 3.1-, 5.5-, and 7.6-fold with treatment with 10(-8), 10(-7), and 10(-6) mol/L ATRA, respectively. Rad-NIS-infected cells showed a 4.0-fold increase in (125)I uptake. Treatment of Rad-NIS-infected cells with 10(-8), 10(-7), and 10(-6) mol/L ATRA increased (125)I uptake by 4.9-, 8.2-, and 27.6-fold, respectively, compared with wild-type MCF-7 cells. The level of NIS expression in Rad-NIS-infected MCF-7 cells treated with 10(-6) mol/L ATRA (245.0 +/- 13.7 pmol/10(6) cells) was much greater than the sum of the expression levels seen in ATRA-treated wild-type cells and Rad-NIS-infected wild-type cells. CONCLUSION: Retinoic acid increases adenovirus-mediated NIS expression in MCF-7 cells. Our results indicate that improved efficiency of NIS gene therapy or reporter imaging in breast cancer may be possible with retinoic acid treatment.     

Anterior translocaton of pulmonary artery without aortic transection in repair of tetralogy of Fallot with absent pulmonary valve.

We developed a technique of translocation of the pulmonary artery anterior to the ascending aorta without transection of the aorta in the repair of tetralogy of Fallot with absent pulmonary valve. Our technique includes detachment of the main pulmonary artery (MPA) from the pulmonary annulus, vertical division of the MPA, anterior translocation of the pulmonary artery with patch augmentation between the vertically divided MPA.     

腹腔镜在胃癌根治术的应用进展

近年来有关早期胃癌的微创治疗进展很快，并已取得国内外的共识。对进展期胃癌应用腹腔镜行胃癌根治术尽管已经取得了较好的临床效果，但仍尚待前瞻性多中心临床随机对照研究。从应用前景看，随着术者技术的完善、观念的改变、经验的积累、手术器械的不断改进，腹腔镜胃癌根治术必将在胃癌手术中扮演越来越重要的角色。