Gastro-oesophageal reflux disease: Medical or surgical treatment? Report of an interactive workshop

Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper.     

Cultured chinese-hamster ovary cells lack a transferable x-radiation resistance factor

We determined if we could transfer X-radiation resistance from CHO AA8 cells to their radiosensitive, mutant V3 cells by several methods. These methods include co-incubating the two cell lines for three days before irradiation, adding heavily-irradiated AA8 to V3 cells following irradiation of the latter and then co-incubating these cells for at least eight days during the colony-forming assay and lastly, adding conditioned medium from unirradiated, subconfluent AA8 cells to V3 cultures and incubating for two days before irradiation. None of these procedures enhanced the clonogenic survival of the V3 cells to a single dose of 4 Gy X-radiation. Adding heavily-irradiated V3, instead of AA8, cells did not increase the clonogenic survival of the 4 Gy-irradiated V3 cells either, indicating that there was no autocrine mode of action. Moreover, adding conditioned medium from a related CHO cell line, K1, to its own radiosensitive, mutant 5-11 and incubating for two days before irradiation did not enhance clonogenic survival of the latter to a single dose of 3 Gy X-radiation. We therefore conclude that it is unlikely that CHO cells have the X-radiation resistance factor that has been reported in some mouse melanoma cell lines by other investigators.     

Bacterial and mammalian DNA alkyltransferases sensitize Escherichia coli to the lethal and mutagenic effects of dibromoalkanes

Here we confirm and extend our previous studies demonstrating that the mutagenic potency of 1,2-dibromoethane (DBE) and dibromomethane (DBM) is markedly enhanced (not prevented) in bacteria expressing the O6- alkylguanine-DNA alkyltransferase (ATase) encoded by the Escherichia coli ogt gene. We demonstrate that, in close parallel with mutagenesis, the Ogt ATase sensitizes the bacteria to the lethal effects of these carcinogens, suggesting that one or more of the potentially mutagenic lesions induced by DBE and DBM in the presence of Ogt has additional lethal capacity. We further demonstrate that the sensitization to both lethality and mutagenesis by DBE and DBM is a property shared by other DNA alkyltransferases. This objective was accomplished by quantifying the induction of mutations and lethal events in ogt- ada- E. coli expressing an exogenous bacterial or mammalian ATase from a multicopy plasmid. Mammalian recombinant ATases enhanced the lethal and mutagenic actions of DBE and suppressed the lack of sensitivity of the vector- transformed bacteria to DBM. In most cases the order of effectiveness of the ATases ranked: murine > human > Ogt > rat. Further comparisons included the full-length Ada ATase from E. coli and a truncated Ada version (T-ada) that retains the O6-methylguanine binding domain of the protein. The full-length Ada ATase was effective in enhancing the lethality but not the mutagenicity induced by DBE and DBM. The T-ada ATase provided less sensitization than Ada to lethality by DBE, but of the three bacterial ATases T-ada yielded the highest sensitization to mutagenesis by this compound. T-ada and Ada ATases were in general less effective than the mammalian versions, with the exception of the rat recombinant ATase. The effectiveness of the different mammalian and bacterial ATases in promoting the deleterious actions of dibromoalkanes was compared with the effectiveness of these proteins in suppressing the lethal and mutagenic effects induced by N-nitroso-N-methylurea. The ability to sensitize E. coli to the lethal and mutagenic effects of DBE and DBM seems restricted to DNA alkyltransferase, since overexpression of thioredoxin (Trx) or glutaredoxin (Grx1) in ogt- ada- cells showed no effect, in spite of the reported potential of bioactive dihaloethane- derived species to alkylate Trx.      

Sequence comparison of human and yeast telomeres identifies structurally distinct subtelomeric domains

We have sequenced and compared DNA from the ends of three human chromosomes: 4p, 16p and 22q. In all cases the pro-terminal regions are subdivided by degenerate (TTAGGG)n repeats into distal and proximal sub- domains with entirely different patterns of homology to other chromosome ends. The distal regions contain numerous, short (<2 kb) segments of interrupted homology to many other human telomeric regions. The proximal regions show much longer (approximately 10-40 kb) uninterrupted homology to a few chromosome ends. A comparison of all yeast subtelomeric regions indicates that they too are subdivided by degenerate TTAGGG repeats into distal and proximal sub-domains with similarly different patterns of identity to other non-homologous chromosome ends. Sequence comparisons indicate that the distal and proximal sub-domains do not interact with each other and that they interact quite differently with the corresponding regions on other, non- homologous, chromosomes. These findings suggest that the degenerate TTAGGG repeats identify a previously unrecognized, evolutionarily conserved boundary between remarkably different subtelomeric domains.      

老年人血浆溶血磷脂酸和磷脂酸水平综合干预后的效果比较

目的:通过对老年人进行血浆溶血磷脂酸和磷脂酸的筛检,从而认识血浆溶血磷脂酸和磷脂酸在血栓预防中的作用。方法:对2004-04/07期间的1657名和2005-04/07期间的1748名离休干部进行血浆溶血磷脂酸和磷脂酸含量测定,并对溶血磷脂酸>3.0μmol/L和磷脂酸>5.0μmol/L的阳性人员进行药物干预。同时,选择2004年溶血磷脂酸和/或磷脂酸阳性人员119人,随机分为两组:①干预组(n=72):男63人,女9人,平均年龄78岁。口服阿司匹林100mg/d,持续1个月。②对照组(n=47):男42人,女5人,平均年龄76岁。干预后,测定两组血浆中溶血磷脂酸和磷脂酸的含量。结果:纳入对象全部进入结果分析。2005年磷脂酸及血浆溶血磷脂酸 磷脂酸阳性率均明显低于2004年(P<0.01),尤其是磷脂酸的阳性率降低的更为明显。2005年血浆溶血磷脂酸和磷脂酸的平均值均明显低于2004年(P<0.01)。干预组干预后血浆溶血磷脂酸和磷脂酸明显低于干预前及对照组(P<0.01)。结论:①血浆溶血磷脂酸和磷脂酸的测定可作为血栓预警和了解抗血栓药物疗效的一种手段。②阿司匹林干预后,血浆溶血磷脂酸和磷脂酸的含量均降低,可作为一种降低缺血性疾病发生率的有效途径。