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Biomedical subjects

D Guo

Publications and source records attributed to D Guo.

9 recordsLinked to original sources

Inhibition of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-DNA binding by chlorophyllin: studies of enzyme inhibition and molecular complex formation.

Chlorophyllin (CHL), a copper/sodium salt of chlorophyll used in the treatment of geriatric patients, is an anti-mutagen that has been demonstrated to inhibit carcinogen--DNA binding in vivo. To study the mechanism of inhibition, the microsomal metabolism of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and the kinetics of IQ--DNA binding were investigated in the presence and absence of CHL. In time-course studies, CHL produced greater than 80% inhibition of IQ--DNA binding and blocked the metabolism of IQ, such that 80% of the initial dose of carcinogen was recovered unmetabolized from the incubations after 1 h. Kinetic constants were determined for the in vitro DNA binding reaction, with the reaction rate measured as 'pmol IQ bound/mg DNA/min/mg microsomal protein'. Without altering V(max), the Km of the IQ--DNA binding reaction was increased by CHL, and the replot of Km/V(max) versus CHL concentration yielded a straight line with an inhibitor constant of 58.3 microM CHL. Spectrophotometric studies provided evidence in vitro for the formation of a non-covalent complex between CHL and IQ. The CHL--IQ complex had a stoichiometric ratio of 2:1 (mole ratio method) and an apparent dissociation constant from the Benesi-Hilderbrand plot of 1.41 x 10(-4)M at pH 7.4. These results are discussed in the context of a CHL inhibitory mechanism involving enzyme inhibition and molecular complex formation.

Animals

[Textual study of Chinese drug loulu].

Through a critical study of Loulu in ancient Chinese herbals, it is concluded that the botanical origin of Loulu should be Qizhou Loulu, the dried root of Rhaponticum uniflorum of family Compositae, while the dried root of Echinops latifolius, which is also one of the species specified in Chinese Pharmacopoeia, should not be used as Loulu because of its deficiency of herbal evidences and totally different chemical constituents from those of the former. It is therefore recommended the latter plant be deleted from the Chinese Pharmacopoeia.

Drugs, Chinese Herbal

Comparison of different information content models by using two strategies: development of the best information algorithm for Iliad.

Iliad is a diagnostic expert system for internal medicine. Iliad's "best information" mode is used to determine the most cost-effective findings to pursue next at any stage of a work-up. The "best information" algorithm combines an information content calculation together with a cost factor. The calculations then provide a rank-ordering of the alternative patient findings according to cost-effectiveness. The authors evaluated five information content models under two different strategies. The first, the single-frame strategy, considers findings only within the context of each individual disease frame. The second, the across-frame strategy, considers the information that a single finding could provide across several diseases. The study found that (1) a version of Shannon's information model performed the best under both strategies---this finding confirms the result of a previous independent study, (2) the across-frame strategy was preferred over the single-frame strategy.

Algorithms

Exploring a new best information algorithm for Iliad.

Iliad is a diagnostic expert system for internal medicine. One important feature that Iliad offers is the ability to analyze a particular patient case and to determine the most cost-effective method for pursuing the work-up. Iliad's current "best information" algorithm has not been previously validated and compared to other potential algorithms. Therefore, this paper presents a comparison of four new algorithms to the current algorithm. The basis for this comparison was eighteen "vignette" cases derived from real patient cases from the University of Utah Medical Center. The results indicated that the current algorithm can be significantly improved. More promising algorithms are suggested for future investigation.

Algorithms

New hydrophilicity scale derived from high-performance liquid chromatography peptide retention data: correlation of predicted surface residues with antigenicity and X-ray-derived accessible sites.

A new set of hydrophilicity high-performance liquid chromatography (HPLC) parameters is presented. These parameters were derived from the retention times of 20 model synthetic peptides, Ac-Gly-X-X-(Leu)3-(Lys)2-amide, where X was substituted with the 20 amino acids found in proteins. Since hydrophilicity parameters have been used extensively in algorithms to predict which amino acid residues are antigenic, we have compared the profiles generated by our new set of hydrophilic HPLC parameters on the same scale as nine other sets of parameters. Generally, it was found that the HPLC parameters obtained in this study correlated best with antigenicity. In addition, it was shown that a combination of the three best parameters for predicting antigenicity further improved the predictions. These predicted surface sites or, in other words, the hydrophilic, accessible, or mobile regions were then correlated to the known antigenic sites from immunological studies and accessible sites determined by X-ray crystallographic data for several proteins.

Amino Acids

The adverse effect of marginally higher lead level on intelligence development of children: a Shanghai study.

We surveyed 128 preschool children in a lead-polluted area in Shanghai to study the relationship between blood lead level and neuropsychological functions, assessed by age-appropriate psychological tests. The geometric means of blood lead level was 21.7 + -10.8 micrograms/dl. Of 47 children aged below 30 months, there was no significant difference in BSID indices between the high and low lead subjects, although the high lead children tended to have poorer development scores than the low lead ones. On the other hand, of 81 children older than 46 months, the WPPSI IQ scores showed highly significant negative correlation with blood lead level. Step-wise regression and multiple analysis of covariance techniques were employed to find out and control the confounding factors. Even when 21 non-lead variables were considered, the IQ difference between high and low lead groups remained statistically significant. We concluded that the children, especially those older than 46 months, in the area investigated, did suffer from lead toxicity causing impairment in intelligence development. We support the view that marginally higher lead level in children should be taken seriously.

Age Factors