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Biomedical subjects

C Li

Publications and source records attributed to C Li.

At least 1,225 records · Page 68Linked to original sources

Synthesis and biological evaluation of tetramisole analogues as inhibitors of alkaline phosphatase of the 6-thiopurine-resistant tumor sarcoma 180/TG.

Tetramisole and its analogues are potent inhibitors of alkaline phosphatase, including isoenzymes of Sarcoma 180/TG which appear to be involved in the mechanism of resistance of this neoplastic cell line to the 6-thiopurines. To determine the requirement for the thiazole ring system of tetramisole for inhibitor potency, 2,3,5,6-tetrahydro-6-phenylimidazo[2,1-b]oxazole, 2,3-dihydro-6-phenylimidazo[2,1-b]oxazole, and 2,3,5,6-phenylimidazo[2,1-a]imidazole were synthesized and tested for inhibitory activity against alkaline phosphatase isolated from Sarcoma 180/TG. The results indicate that 2,3,5,6-tetrahydro-6-phenylimidazo[2,1-b]oxazole caused 50% inhibition at 0.21 mM, while the other synthesized compounds were inactive at a concentration of 1 mM; in contrast, tetramisole required only 0.045 mM for 50% inhibition of alkaline phosphatase activity. The findings support the concept that the thiazole ring system of the tetramisole structure is required for maximum inhibitory potency of this series against alkaline phosphatase.

Alkaline Phosphatase↗

Immunologic and biologic activity of oxytocin in midtrimester pregnancy.

Immunologic and biologic activity of oxytocin (OT) were studied by simultaneous monitoring of plasma OT measured by radioimmunoassay (RIA) and uterine contractility measured by recording of intrauterine pressures during the step-up rate of infusion of synthetic OT. The results in 11 patients with midtrimester pregnancy and step-up increase of OT infusion by 20 mU. showed a positive correlation of the increase of plasma OT and uterine contractility only at the plasma OT levels of 20 to 60 muU. per milliliter and only with hypertonic contractility but no correlation at plasma levels below and above this range. The lack of correlation of "dose and response" either prior to OT infusion or during low or very high rate of infusion suggests that other factors than merely the quantity of plasma OT are involved in determining the degree of uterine response.

Abortion, Induced↗

Disposition of pirprofen, a new anti-inflammatory drug.

Plasma and urine concentrations of 2-(3-chloro-4[3-pyrrolinyl]phenyl) propionic acid, pirprofen, a new nonsteroidal anti-inflammatory compound, are described for normal male volunteers receiving one or more doses of the drug. Orally administered pirprofen is rapidly and almost completely absorbed from the gastrointestinal tract, resulting in maximum plasma levels in 1 to 2 hr. Mean peak levels are 23 microng/ml after an oral pirprofen dose of 200 mg; lower doses given proportionally lower levels. Administration 1 hr after a meal slightly delays the peak plasma level, but the extent of absorption is not affected significantly. Administration of pirprofen, 150 mg, 4 times daily, or 200 mg, 3 times daily, results in nearly identical plasma levels at steady-state. Pirprofen has an apparent elimination half-life of about 7 hr. The results obtained from a 200-mg pirprofen-14C dose indicate that excretion of the drug occurs primarily by the renal route in the form of metabolites and is essentially complete within 24 hr. In urine, less than 5% of the administered dose is accounted for as unchanged drug.

Adolescent↗

Chiral resolution of four major flavanones in post-administrative urine of Chinese herbal medicines by HPLC on macroporous silica gel coated with cellulose tris(3,5-dimethylphenylcarbamate).

Direct chiral resolution of four major flavanones recovered from post-administrative urine of the traditional Chinese medicines Daisaiko-to and Shosaiko-to was achieved by high-performance liquid chromatography (HPLC) on macroporous silica gel coated with cellulose tris(3,5-dimethylphenylcarbamate), Chiralcel OD. Chromatographic conditions were optimized so as to attain satisfactory enantiomeric resolution of the polysubstituted flavanones. Urinary liquiritigenin and naringenin were considerable mixtures of R and S-enantiomers, while S-enantiomers of dihydrowogonin and dihydrooroxylin A were predominantly excreted. Our chiral HPLC techniques can be applied to pharmacokinetical evaluation of the chiral flavanone enantiomers following oral administration of the herbal medicines.

Administration, Oral↗

Stopping a clinical trial early: frequentist and Bayesian approaches applied to a CALGB trial in non-small-cell lung cancer.

In May 1984, the Cancer and Leukemia Group B (CALGB) opened a phase III clinical trial for patients with stage III non-small-cell lung cancer (NSCLC). The experimental design entailed randomization of 240 patients equally to one of two treatments: radiotherapy alone or chemotherapy followed by radiotherapy. The original design was a fixed sample size design with the intent to analyse the results after 190 deaths. Shortly after the trial began, it was decided to apply group sequential concepts by using a truncated O'Brien-Fleming stopping rule, implemented via a Lan-DeMets alpha-spending function. A study monitoring committee was established to review the analyses as they were produced. The study was stopped at the fifth interim analysis in May 1987 after 155 eligible patients had been entered. This paper reviews the statistical and other considerations leading to this decision and presents later follow-up information on these patients. Some Bayesian alternatives to the standard frequentist approaches are also explored and it is demonstrated how these alternatives provide a natural way to address many of the issues raised in monitoring clinical trials.

Bayes Theorem↗

Microarray profiling of gene expression patterns in bladder tumor cells treated with genistein.

Microarray technology was used to gain an insight into the molecular events of tumor cell growth inhibition mediated by the soy isoflavone genistein. For this, a susceptible bladder tumor line TCCSUP was treated with the inhibitory dose (50 microM) of genistein for various periods of time, followed by mRNA isolations, cDNA probe preparations, and hybridization individually to cDNA chips containing 884 sequence-verified known human genes. After analyzing the hybridization signals with a simple quantitative method developed by this study, we detected that egr-1, whose expression has been associated with proliferation and differentiation, was transiently induced and this expression pattern was later confirmed by RT-PCR. Thus, microarray technology is a reliable and powerful tool for profiling gene expression patterns in many biological systems related to cancer. We further detected many groups of genes with distinct expression profiles and most of them encode for proteins that regulate the signal transduction or the cell cycle pathways. These genes warrant further investigation as regards their roles in the susceptibility of the tumor cell line to the antitumor drug.

Antineoplastic Agents↗

Carotid ligation alters cholecystokinin-8 (CCK-8) immunoreactivity in gerbil brains.

The unilateral or bilateral carotid arteries were ligated in gerbils used as a model of cerebral ischemia. The effect of different times of bilateral ischemia on the content of CCK-8 in fore regions of gerbil brain and the effect of 30 min of unilateral ischemia on the content of CCK-8 of the same regions in gerbils with or without neurological signs were observed. Our results show that the content of CCK-8 of cortex, basal ganglia, thalamus and hypothalamus decreased significantly. But, in brain stem it remained basically unchanged no matter whether the ischemia was unilateral or bilateral. This suggests that there is a close relationship between CCK-8 and cerebral ischemia, and raises the possibility that CCK-8 may be involved in cerebral ischemia through a yet unclear mechanism.

Animals↗

The flp-1 propeptide is processed into multiple, highly similar FMRFamide-like peptides in Caenorhabditis elegans.

Previously, we described a gene, flp-1, that encodes seven FMRFamide-like peptides from two alternatively spliced transcripts in the nematode Caenorhabditis elegans. To determine whether all or a subset of the predicted peptides coded for by flp-1 are produced in vivo, we undertook the isolation of FMRFamide-like peptides from C. elegans. Six FLRFamide-containing peptides, all contained within the putative translation products of the flp-1 gene, were isolated from extracts of mixed stage animals. By quantitative PCR analysis of RNA from mixed stage animals, we found that the shorter transcript of flp-1 has a higher level of expression than the longer transcript.

Amino Acid Sequence↗

Leptin receptor expression increases in placenta, but not hypothalamus, during gestation in Mus musculus and Myotis lucifugus.

In addition to effects on appetite and metabolism, the hormone leptin is required for reproduction in mammals. Maternal plasma leptin is increased above non-pregnant levels in all mammals thus far examined, including humans. The increase in plasma leptin appears to result in part from upregulation of adipose leptin secretion (e.g., in mice), or from production and secretion of leptin from the placenta (e.g., in humans and some bats). The placenta may also modulate maternal leptin levels via production of a plasma leptin-binding protein (mice, humans). Thus, the placenta plays a coordinating role in regulation of maternal leptin during pregnancy. In this study, the hypothesis that the placenta is also a target organ for leptin in diverse taxa was tested by examining the expression of leptin receptors (Ob-R) in placentae from species of distantly related mammalian taxa, Mus musculus (the laboratory mouse) and Myotis lucifugus (the little brown myotis, also called the little brown bat). A partial sequence of M. lucifugus Ob-R cDNA was first obtained and found to share approximately 78-88% homology at the nucleotide level with known mammalian Ob-R cDNAs. Using probes and primers designed from this sequence, receptor expression was detected in numerous tissues of M. lucifugus, including placenta, which expressed two major receptor isoforms as judged by molecular size. In both species, Ob-R mRNA expression in placenta significantly increased from early to late gestation. Expression of Ob-R mRNA was not affected by cAMP treatment in vitro. The increase in Ob-R mRNA expression in placenta was specific, since Ob-R mRNA expression did not change during gestation in either species in hypothalamus, the major site of the central actions of leptin. Thus, Ob-R is expressed in placenta throughout gestation in mice and bats, and its expression increases over the course of gestation, which raises the possibility that leptin may exert temporally distinct effects on placental growth or function throughout gestation. Because similar placenta-specific changes in leptin receptor expression occurred in species from distantly related mammalian taxa which collectively comprise approximately 70% of all known mammalian species, it is possible that placental actions of leptin are conserved across mammals, even in those species (such as the Swiss-Webster strain of mouse) in which the placenta does not itself produce leptin.

Animals↗

Force analysis of the belly gutter and Capener splints.

In the management of hand injuries resulting from trauma or diseases like rheumatoid arthritis, hand therapists often design static and dynamic splints to rest and protect joints, provide stability, and enhance joint motion. However, the literature provides little help in analyzing the forces of a splint acting on a digit. This paper studies the forces generated by two different finger splints acting on the proximal interphalangeal joint (PIP) of the finger. The principles of force analysis are based on the Fess and Philips model of mechanics. Factors that affect the resultant forces generated by each splint design are identified, and the properties of each splint are discussed. Although the force generated by the two types of splints may vary only slightly, special features of each splint should be seriously taken into consideration in clinical application.

Contracture↗