PubMed · 13995347
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Y UMEGAKI, M TAKIZAWA. 1963-05-25. [Scanning automatic isodose plotter].. https://pubmed.ncbi.nlm.nih.gov/13995347/
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The synthesis of N4-benzoyl-5'-O-dimethoxytrityl-2',3'-dideoxy-3'-thiocytidine and its phosphorothioamidite is described for the first time, together with a shortened procedure for the preparation of 5'-O-dimethoxytrityl-3'-deoxy-3'-thiothymidine and its corresponding phosphorothioamidite. The first fully automated coupling procedure for the incorporation of a phosphorothioamidite into a synthetic oligodeoxynucleotide has been developed, which conveniently uses routine activators and reagents. Coupling yields using this protocol were in the range of 85-90% and good yields of singularly modified oligonucleotides were obtained. Coupling yields were also equally good when performed on either a 0.2 or 1 micro mol reaction column, thus facilitating large scale syntheses required for mechanistic studies.
B cell chronic lymphocytic leukemia (B-CLL) is characterized by a highly variable clinical course. Recurrent chromosomal imbalances provide significant prognostic markers. Risk-adapted therapy based on genomic alterations has become an option that is currently being tested in clinical trials. To supply a robust tool for such large scale studies, we developed a comprehensive DNA microarray dedicated to the automated analysis of recurrent genomic imbalances in B-CLL by array-based comparative genomic hybridization (matrix-CGH). Validation of this chip in a series of 106 B-CLL cases revealed a high specificity and sensitivity that fulfils the criteria for application in clinical oncology. This chip is immediately applicable within clinical B-CLL treatment trials that evaluate whether B-CLL cases with distinct chromosomal abnormalities should be treated with chemotherapy of different intensities and/or stem cell transplantation. Through the control set of DNA fragments equally distributed over the genome, recurrent genomic imbalances were discovered: trisomy of chromosome 19 and gain of the MYCN oncogene correlating with an elevation of MYCN mRNA expression.
Tar and nicotine deliveries of cigarettes measured using current standardized smoking machine protocols provide poor estimates of smoke exposure. The characteristics of human smoking behavior vary considerably and differ from the rigid parameters used with current standardized smoking machine protocols. Current alternatives, including measurement of biomarkers, are invasive, time-dependent, and can be too expensive to be used as mechanisms for carrying out large-scale investigations required to help determine the influence of cigarette design on smoking behaviors. To obtain more reasonable estimates of mainstream smoke exposure, we developed a method to quantitatively measure solanesol, a naturally occurring component in tobacco that is deposited during smoking in the cigarette filter butt. Quantification of solanesol extracted from the filters using liquid chromatography and tandem mass spectrometry is efficient, rapid, and extremely reliable. We found that the amount of solanesol deposited in a cigarette filter is related to the mainstream smoke deliveries of tar and nicotine under a variety of smoking conditions. In addition, the amount of solanesol trapped in the filter remains stable at least 4 weeks after smoking. Measuring solanesol in cigarette filters as an exposure marker provides a noninvasive means to obtain reasonable estimates of mainstream tar and nicotine smoke deliveries under a wide variety of smoking conditions.