麦冬类中药组织切片计算机三维重建图鉴

利用计算机技术实现麦冬类中药组织连续切片三维重建与动态显示,为计算机辅助生药学鉴定和教学提供了新的三维图像技术和研究资料。     

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.     

Low-artifact intravascular devices: MR imaging evaluation

Flow-phantom magnetic resonance (MR) imaging, with use of both spin-echo (SE) and gradient-echo (GRE) techniques at 1.5 T, was performed on the percutaneous Greenfield (beta-III titanium alloy [TMA wire]), Amplatz (MP32-N alloy), and Simon nitinol filters and TMA wire facsimiles of the bird's nest, Gunther, new retrievable, and Amplatz vena caval filters. SE imaging allowed detection of thrombi as small as 5 X 5 mm trapped within the percutaneous Greenfield, Simon nitinol, and TMA-wire facsimile filters; with the MP32-N Amplatz filter, a larger volume of thrombus (10 X 20-mm clots) was necessary for clot detection. GRE imaging allowed detection of intraluminal tilting of the percutaneous Greenfield and facsimile Amplatz (TMA-wire) filters. GRE imaging was useful for demonstrating postfilter turbulence due to clots, which was greatest for the Amplatz filter. Imaging of facsimile vascular devices made of tantalum or TMA wire did not cause the severe "black-hole" MR artifacts typical of the stainless-steel devices. SE and GRE imaging were very useful for determining caval patency in two patients with previously placed Mobin-Uddin filters. Noninvasive MR evaluation of blood vessels in the presence of a variety of low-artifact intravascular devices appears feasible.     

Mechanisms of carcinogenicity/chemotherapy by O6-methylguanine

Alkylating agents are a structurally diverse group of compounds that cause a wide range of biological effects, including cell death, mutation and cancer. DNA damaged by these agents contains widely different amounts of 12 alkylated purines/pyrimidines and two phosphotriester isomers. The biological effects appear to be mediated predominantly by attack at the O(6) position of guanine. DNA extracted from various normal human tissues contains detectable levels of O(6)-alkylguanine, the source of which has not been defined. Given that, following DNA replication, this lesion cannot only generate point mutations but can also initiate mismatch repair-mediated DNA recombination and cell death, it seems worthwhile to consider the possible contribution of these events and cell killing to the aetiology of human cancer. There is increasing evidence that point mutations are not the only mechanism involved in malignant transformation by alkylating agents. Some cancer chemotherapeutic agents exploit the cytotoxic effects of O(6)-alkylguanine and an understanding of the processing of this lesion has allowed strategies to be developed that should increase the effectiveness of such agents.     

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.      

Protection of Chinese hamster cells against the cytotoxic and mutagenic effects of alkylating agents by transfection of the Escherichia coli alkyltransferase gene and a truncated derivative

The cytotoxic and mutagenic effects of various monofunctionaland bifunctional alkylating agents have been assessed in V79Chinese hamster cells that express either the entire O⁶-alkylguanine(O⁶AG) and alkylphosphotriester alkyltransferase (ATase) gene(clone 8 cells) or a truncated form that codes only for O⁶AGATase activity (clone SB cells). Protection ratios, as determinedby D₃₇ values, were greater for clone 8 cells than for SB cells.Significant protection against the mutagenic effects of N-methyl-N-nitrosoureaand ethylmethanesulphonate at the hypoxanthine phosphoribosyltransferase(HPRT) locus was observed in clone 8 and SB cells. Streptozotocinand the haloethyl nitrosoureas, chlorozotocin and bis-chloroethylnitrosoureawere less efficient in inducing HPRT-deficient mutants and asmaller degree of protection was afforded by the transfectedgenes. This is possibly due to the propensity of these compoundsto induce multi-locus deletions. Southern analysis of DNA fromclone 8 and SB cells indicated the presence of multiple copiesof the plasmid integrated into clone 8 cells but few copiesin clone SB cells. The copy number did not change but ATaselevels fell when cells were grown in the absence of G418. ²Present address: Corporate Biosciences Laboratory, ICI plc,The Heath, Runcorn, Cheshire, UK      

O6-Methylguanine methyltransferase activity is increased in rat tissues by ionising radiation

The effect of whole body ionising radiation from a linear acceleratoron rat tissue O⁶-methylguanine (O⁶-meG) methyl-transferase (MT)activity has been assessed using an assay which measures thetransfer of ³H-radioactivity from ³H-methylated substrate DNAto protein. The maximal effect occurred 2 days after a 1 kraddose, at which time activity in liver extracts was increased5-fold in two different rat strains. Activity in lung and kidneywas increased 4- and 2-fold, respectively. Similar degrees ofenhancement were found in these three tissues using an h.p.l.c.method for measuring MT activity. The increase in activity wasreflected in an increased capacity to repair O⁶-meG producedin liver DNA by administration of [¹⁴C]dimethylnitrosamine (DMN):this effect was dose dependent, being detectable after 30 radsand maximal after 600 rads. Incorporation of labelled breakdownproducts of the DMN into adenine in DNA increased as the doseradiation increased suggesting an inhibition of DNA synthesis.The implications of these results for the mechanism of enhancingO⁶-meG repair are discussed.     

Clinical pharmacology of oral and intravenous 4-demethoxydaunorubicin

Summary The clinical pharmacology of 4-demethoxydaunorubicin (4-DMDNR) was studied in 28 patients with advanced breast cancer, using a sensitive reverse-phase HPLC technique. All patients had normal renal and hepatic function. The serum levels of 4-DMDNR after a single i.v. bolus injection followed a triple exponential decay curve (T1/2=9.6 min, T1/2=3.2 h and T1/2=34.7 h) and conformed to a three-compartment model. Comparison of the area under the curve (AUC) and urinary excretion for the oral and i.v routes suggests an oral bioavailability of approximately 24%. In patients treated with a schedule of weekly oral administration for periods of up to 12 months there was no significant alteration in either AUC or elimination half-life for the parent drug or its principal metabolite 13-OH4DMDNR. Moreover, there was no evidence of accumulation of the metabolite although measurable amounts were present 7 days after administration of 4-DMDNR.This work was supported by the Cancer Research Campaign and Farmitalia Carlo Erba Ltd