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Biomedical subjects

R H Liu

Publications and source records attributed to R H Liu.

85 records · Page 5Linked to original sources

Hemoglobin Chongqing [alpha 2(NA2)Leu----Arg] and hemoglobin Harbin [alpha 16(A14)Lys----Met] found in China.

Hemoglobin Chongqing is a new slowly-moving and unstable hemoglobin variant with a high oxygen affinity, that was discovered in five members of a Chinese family in the suburb of Chongqing. Hemoglobin Harbin is another new rapidly-moving hemoglobin variant with slightly reduced stability and slightly increased oxygen affinity, found in a Chinese woman living in Harbin. The relative amounts of these two variants in the propositi were about 9% and 18%, respectively. Sequence analyses identified a Leu----Arg substitution at position alpha 2(NA2) of Hb Chongqing, and a Lys----Met substitution at position alpha 16(A14) of Hb Harbin.

Adult↗

Interaction of inferior olivary nucleus with reflex bradycardia and tachycardia in the cat.

In chloralose-urethane anesthetized cats, stimulation of the ION, apart from directly producing cardioinhibition, was capable of interacting antagonistically with reflex tachycardia (induced by nitroglycerin) and synergistically with reflex bradycardia (induced by phenylephrine). The degree of the potentiation or antagonism was greater than the sum of the individually elicited responses. It was also directly related to the dose of the drugs and the intensity of the stimulating pulse frequency delivered to the nucleus. The similarity in natures of both cardio-inhibitory mechanisms of the ION and gigantocellular reticular nucleus (GRN) has been discussed. We infer that the ION, GRN, nitroglycerin-induced reflex tachycardia and phenylephrine-induced reflex bradycardia may share a final common neural mechanism which function to suppress heart rate. The neurons in the dorsal motor (DM)/solitary (SN) nuclei may be a good candidate, because bilateral vagotomy or unilateral vagotomy with a contralateral DM/SN destruction substantially abolished the cardio-inhibitory effect of both GRN and ION.

Animals↗

Comparative in vitro antitumor activity of homoharringtonine and harringtonine against clonogenic human tumor cells.

Harringtonine and its derivative homoharringtonine are ester-containing anti-leukemic alkaloids isolated from the tree Cephalotaxus harringtonia. In order to compare their antitumor activity against solid tumors, in vitro culture of fresh tumor cells from 23 patients was carried out with a soft agar assay system. Tumor cells were exposed to 0.001-1.0 micrograms/ml of each agent for either 1 h prior to plating or by continuous exposure. Significant antitumor activity was noted for harringtonine in ovarian and endometrial carcinoma at the 0.01 micrograms/ml concentration. In the continuous exposure studies, homoharringtonine proved to be more potent than harringtonine. Significant antitumor activity of homoharringtonine was noted in sarcoma and breast cancer as well as in ovarian and endometrial carcinoma. In the continuous exposure studies the mean area under the survival-concentration curve was significantly less for homoharringtonine than for harringtonine (5.04 +/- 3.87 and 6.15 +/- 3.46, respectively (p less than 0.005). The ratio of mean ID50 (harringtonine/homoharringtonine) was 5.2. However, there was no significant difference between those two agents with a 1 h exposure. Our results suggest that homoharringtonine and harringtonine may be of use in selected solid tumors, and that homoharringtonine has a greater degree of colony inhibition with continuous exposure.

Alkaloids↗

Antitumor activity of didemnin B in the human tumor stem cell assay.

In vitro studies of the schedule dependency and cytotoxicity of didemnin B, a novel depsipeptide isolated from a Carribean tunicate (Didemnidae), were carried out in fresh tumor cells obtained from biopsies from 39 cancer patients using the human tumor stem cell assay. Two schedules of drug exposure were examined (1 h and continuous exposure in the agar). Tumor cells from nine of 26 patients (34.6%) showed reduced survival of tumor-colony forming units to 30% of control or less at the 0.01 microgram level in the continuous exposure studies. Cells from eight of 17 patients (47%) showed a similar degree of sensitivity to didemnin after a 1-h exposure to 0.1 microgram prior to plating. The median ID50 values were 4.2 X 10(-3) micrograms/ml and 46 X 10(-3) micrograms/ml for continuous and 1-h exposures, respectively. A clear dose-response relationship was observed with both dosage schedules. Comparison of the slopes of the continuous and 1-h exposures and of the ID50 of the drug schedules suggests that didemnin is a cell-cycle-non-specific cytotoxic agent. Significant in vitro antitumor activity was observed at low concentrations against carcinomas of the breast, ovary, and kidney, and also mesothelioma and sarcoma. These results can provide pharmacologic goals to be achieved in phase I clinical trial. Further in vitro testing should help select tumor types for study in phase II trials of this very promising new anticancer drug.

Antibiotics, Antineoplastic↗

Correlations on radioimmunoassay, fluorescence polarization immunoassay, and enzyme immunoassay of cannabis metabolites with gas chromatography/mass spectrometry analysis of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid in urine specimens.

Results obtained from three commercial immunoassay kits, Abuscreen, TDx, and EMIT, commonly used for the initial test of urine cannabinoids (and metabolites) were correlated with the 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (9-THC-COOH) concentration as determined by GC/MS. Correlation coefficients obtained based on 26 (out of 1359 total sample population) highly relevant samples, are 0.601 and 0.438 for Abuscreen and TDx. Correlation coefficients obtained from a parallel study on a different set of 47 (out of 5070 total sample population) highly relevant specimens are 0.658 and 0.575 for Abuscreen and Emit. The immunoassay concentration levels, that correspond to the commonly used 15 ng/ml GC/MS cutoff value for 9-THC-COOH, as calculated from the regression equations are 82 ng/ml and 75 ng/ml for TDx and EMIT and 120 ng/ml and 72 ng/ml for Abuscreen manufactured at two different time periods. The difference of these calculated corresponding concentrations provides quantitative evidence of the reagent specificity differences.

Cannabinoids↗

Selection of an appropriate initial test cutoff concentration for workplace drug urinalysis--Cannabis example.

Apparent analyte concentration (equivalent of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid [9-THC-COOH]) obtained by radioimmunoassay (RIA) for cannabinoids using reagents manufactured at four different periods (from the same manufacturer) and specific 9-THC-COOH concentration as determined by GC/MS are examined for the significance of their correlation. The resulting regression equations are then used to estimate the apparent RIA analyte concentrations of reagents manufactured at different time periods that are equivalent to a specific 9-THC-COOH concentration. Correlation coefficients of the regression analysis improve from approximately 0.4 to 0.7 in parallel with the increasing reagent specificity. The apparent RIA analyte concentrations that correspond to 15 ng/mL 9-THC-COOH decrease from about 110 to 50 ng/mL again in parallel with the increasing reagent specificity. These findings empirically demonstrate that reagent specificity is the determining factor of the resulting apparent RIA analyte concentration when testing samples that contain 9-THC-COOH and other metabolites (derived from marijuana exposure). Thus, if the 9-THC-COOH concentration as determined by GC/MS is of primary concern, the initial test cutoff concentration should be adjusted in accordance with the specificity of the reagent used.

Dronabinol↗

Chemical derivatization and the selection of deuterated internal standard for quantitative determination--methamphetamine example.

Use of an isotopic analogue of the analyte as the internal standard in a quantitative gas chromatography-mass spectrometry targeted-compound-analysis protocol is often hindered by the availability of an adequate number (typically three for the drug/metabolite and two for the isotopic analogue) of sufficiently high mass ions that can be attributed to each member of the pair and are sufficiently free of interference by the contribution from the other component of the pair, a phenomenon termed "cross-contribution". Methamphetamine (MA) is selected as the exemplar compound to examine the effectiveness in using different chemical derivatization routes to produce derivatized analyte-isotopic analogue pairs that can generate more favorable mass spectrometric data to meet this analytical requirement. Trimethylsilyl-, trichloroacetyl-, and pentafluoropropionyl-derivatization and MA-d5, MA-d8, and MA-d9 are studied. Data resulting from this study indicate that the number of ion pairs suitable for quantitation and the degree of cross-contribution of these ions vary significantly. These data empirically demonstrate that derivatization methods play a significant role in deciding which deuterated analogue of the analyte provides the most suitable ion pairs that cause the least cross-contribution. The most suitable internal standard varies with the derivatization route adapted for an analytical protocol.

Central Nervous System Stimulants↗

Mechanistic studies on the use of 2H- and 13C-analogues as internal standards in selected ion monitoring GC-MS quantitative determination--butalbital example.

As a part of our study on the use of isotopic analogues as the internal standard (IS) for the quantitation of drug analytes, this article reports on the performance characteristics of 2H5-butalbital and 13C4-butalbital with particular focus on (1) determining and comparing the effectiveness of the 2H- and 13C-analogues in serving as the ISs for quantitation; (2) understanding the "cross-contribution" phenomenon underlying the effectiveness of selected ion pairs used for quantitation purpose; and (3) examining whether the same characteristics, observed in our preliminary report for the secobarbital/2H5-secobarbital/13C4-secobarbital system, also exist in the butalbital/2H5-butalbital/13C4-butalbital system. Adapting similar procedures applied to our previous study on the secobarbital system, we observed that (1) both labeled analogues (13C4-butalbital and 2H5-butalbital) cause more significant cross-contributions to ions designated for butalbital than butalbital to the labeled analogues; (2) compared to 2H5-butalbital, 13C4-butalbital appears to cause less cross-contributions to ions designated for butalbital; (3) cross-contribution between the following ion pairs are minimal: m/z 200/196, 199/195, 185/181 (13C4-butalbital as the IS) and m/z 201/196 (2H5-butalbital as the IS). It is also concluded that the butalbital/2H5-butalbital system exhibits the same concentration dependency phenomenon observed in the secobarbital/ 2H5-secobarbital system, that is, ratios of ion pairs designated for these two isotopic analogues (resulting from routine gas chromatography-mass spectrometry protocol) increase as their concentrations are diluted. (In parallel with the secobarbital/13C4-secobarbital system, the butalbital/13C4-butalbital system does not exhibit this phenomenon.)

Barbiturates↗