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Biomedical subjects

R Liu

Publications and source records attributed to R Liu.

At least 379 records · Page 21Linked to original sources
PubMed1988

Amdinocillin: interaction with other beta-lactam antibiotics for gram-negative bacteria.

Amdinocillin was studied alone and in combination with three other beta-lactam antibiotics (aztreonam, cefoperazone, and ceftriaxone) for activity against gram-negative bacilli. These antibiotic combinations failed to show synergy by the checker-board double-dilution test or by killing kinetic studies. However, amdinocillin did show additive killing action when combined with the other beta-lactam antibiotics studied. Amdinocillin failed to induce or inhibit beta-lactamase production in species of Enterobacteriaceae, but with Pseudomonas aeruginosa, beta-lactamase production was induced. It is concluded that the activity of amdinocillin alone or in combination with another beta-lactam antibiotic should not be more effective in the treatment of infections by gram-negative bacilli than just using the beta-lactam antibiotic alone at a higher dose.

Amdinocillin↗
PubMed1987

Structurally different neuronal nicotinic acetylcholine receptor subtypes purified and characterized using monoclonal antibodies.

Acetylcholine receptors that bind nicotine with high affinity but do not bind alpha-bungarotoxin have recently been immunoaffinity purified from brains of chickens and rats (Whiting and Lindstrom, 1986a, b; Whiting and Lindstrom, 1987a). Antisera to these receptors bind to the nicotinic receptors that regulate cation channel opening on chick ciliary ganglion neurons (Stollberg et al., 1986) and rat PC12 cells (Whiting et al., 1987c). Here we report the preparation and characterization of monoclonal antibodies to chicken brain acetylcholine receptors. These monoclonal antibodies are used to identify 2 nicotinic receptor subtypes in the chicken brain. The 2 subtypes have very similar affinities for nicotine and other cholinergic agonists and antagonists. However, they are structurally distinct, having very similar or identical alpha subunits (Mr 49,000), but different beta subunits (Mr 59,000, or for beta' subunit, Mr 75,000). Evidence is presented that suggests that the subunit stoichiometry of these neuronal nicotinic acetylcholine receptors is alpha n = 2 - 3 beta n = 2 - 3. Different levels of receptor subtype expression were detected in embryonic, compared to adult, chicken brain.

Animals↗
PubMed1985

Salmonella infections in patients with acquired immunodeficiency syndrome.

Salmonella infections occurred in six patients with acquired immunodeficiency syndrome (AIDS) and one patient with probable AIDS. The immune system defects increase the susceptibility of patients with AIDS to salmonella infections. Recognition of salmonellosis in patients with AIDS is important because of a high propensity of this organism to invade the bloodstreams of these patients, and because, unlike other infections in patients with AIDS, this infection can be easily treated.

Acquired Immunodeficiency Syndrome↗
PubMed1984

The dorsal tegmental nucleus: an axoplasmic transport study.

The afferent and efferent connections of the dorsal tegmental nucleus (DTN) were studied in the rat using axoplasmic transport techniques. Horseradish peroxidase (HRP) and Fast Blue were injected stereotaxically into either pars centralis or pars ventromedialis of the DTN, two subdivisions of the nucleus with distinctive connections. The pars centralis is reciprocally connected with the ipsilateral lateral mammillary and interpeduncular nuclei; these projections constitute the major afferent and efferent systems of the DTN. Commissural fibers from the corresponding pars centralis and intrinsic fibers systems are massive and form a complex fiber meshwork within the subnucleus. The prepositus hypoglossi nucleus (ipsilateral) and supragenualis nuclei (bilateral) also project to the pars centralis. Smaller numbers of afferent fibers arise from the lateral habenular nucleus, the posterior hypothalamus and the brainstem reticular formation. The pars ventromedialis of the DTN receives diverse inputs which include the septal nuclei, diagonal band of Broca, preoptic area, anterior and lateral hypothalamus, lateral and medial habenular nuclei, medial mammillary nucleus and many nuclei of the brainstem reticular formation. Based on the differences of connections and cytoarchitecture between the pars centralis and the pars ventromedialis, the pars ventromedialis may be an entity separate from the dorsal tegmental nucleus.

Animals↗
PubMed1984

Antitumor activity of esorubicin in human tumor clonogenic assay with comparisons to doxorubicin.

The new anthracycline analog, esorubicin (4'deoxy-doxorubicin, ESO), was tested against fresh biopsies of human solid tumors in vitro in clonogenic assay and the results were contrasted to those obtained with doxorubicin (DOX). ESO appeared to be significantly more potent on a weight basis than DOX in these studies, and exhibited a spectrum of antitumor activity in vitro that was in general qualitatively similar to that observed with DOX. In vitro antitumor activity was observed in a wide variety of human cancers including anthracycline-sensitive tumor types. ESO has previously been reported to have decreased cardiac toxicity in preclinical models as compared to DOX. Comparative testing of these anthracyclines on granulocyte-macrophage colony-forming units (GM-CFUs) and tumor colony forming units (TCFUs) indicated that the in vitro GM-CFU assay is more sensitive to these myelosuppressive drugs than are TCFUs, and underscores the need for in vivo studies to determine normal tissue toxicity and the therapeutic index of a drug. Early results of phase I studies suggest that with respect to myelosuppression, the maximally tolerated dose of ESO will be about half that of DOX. The increased in vitro antitumor potency observed for ESO and a spectrum of activity (even at one half the dose of DOX) supports the broad testing of ESO in the clinic to determine whether it will prove to be a more effective and less toxic anthracycline.

Cell Survival↗
PubMed1984

Detection of IgG in supernatants of pokeweed mitogen-stimulated human lymphocyte cultures by one step solid-phase radioimmunoassay (SPRIA).

A one step solid phase radioimmunoassay is used as a simple and reproducible method of detection and quantitation of IgG produced by human PBL after stimulation with PWM. Modifications of culture conditions are necessary to make culture supernatants suitable for this assay. Pulsing with PWM must be performed in serum-supplemented culture medium for 4-5 days. After thorough washing, medium is then replaced with serum-free medium. Under these conditions, synthesis and secretion of IgG continues for at least 9 days. The amount of IgG produced by 10(6) normal adult PBL as detected in this system is 0.77 +/- 0.47 micrograms. No close correlation between cell proliferation and IgG synthesis was observed.

Culture Media↗
PubMed1983

A hypo-osmotic medium to disaggregate tumor cell clumps into viable and clonogenic single cells for the human tumor stem cell clonogenic assay.

A hypo-osmolar medium and tissue processing technique is described which is useful for disaggregation of residual human tumor cell clumps persisting after mechanical or enzymatic treatment of solid tumors and malignant effusions. The addition of the hypo-osmolar procedure to the standard methods for disaggregation increased the viable single cell yield in solid tumors by 47% and in malignant effusions by 67%. In 5 of the 26 solid tumor specimens tested in the human tumor stem cell assay, clonogenic single cells were obtained with the hypo-osmolar procedure, whereas no growth was observed using standard methods. Overall, the success rate for clonogenicity increased from 46% to 65% for the 26 solid tumors, with the major improvement occurring in ovarian cancer. Clonogenicity was obtained in 80% of malignant effusions both by standard methods and the hypo-osmolar techniques. The increased total yield of clonogenic cells obtained with this procedure enhances the opportunity for experimental versatility and in vitro drug testing.

Cell Aggregation↗
PubMed1983

Usefulness of abrin as a positive control for the human tumor clonogenic assay.

A series of approaches were tested in order to develop a simple technique for introducing a routine positive control into the Human Tumor Clonogenic Assay. Of the various techniques tested, the best proved to be the addition of the toxic plant lectin abrin to the culture system. When added to the agar underlayer of the culture system so that the final abrin concentration in culture was 10 micrograms/ml, survival of human tumor colony-forming units (TCFU) was reduced to less than 1% of control in 16/34 (47%) of human tumors, to less than 10% in 33/34 (97%) and to less than 30% in all tumors tested (100%). A clear dose-response relationship to fractional survival was observed for individual tumors tested at multiple dose levels of abrin. When the dosage of abrin was reduced to 1 micrograms/ml, survival of TCFU was reduced to less than 30% in 25/28 (89.2%) of experiments. Inclusion of abrin controls in clonogenic assays thus provides an excellent and reproducible positive control to which cytotoxic effects of a variety of therapeutic agents can be compared.

Abrin↗
PubMedDate not supplied

Development of quantitative structure-property relationship models for early ADME evaluation in drug discovery. 1. Aqueous solubility.

A simple QSPR model, based on seven 1D and 2D descriptors and artificial neural network, was developed for fast evaluation of aqueous solubility. The model was able to predict the molar solubility of a diverse set of 1312 organic compounds with an overall correlation coefficient of 0.92 and a standard deviation of 0.72 log unit between the calculated and experimental data. Considering the fact that the estimated uncertainty of the experimental data is no less than 0.5 log unit, the results demonstrate that carefully chosen physically meaningful 1D and 2D descriptors encode sufficient molecular information for fast and reasonably reliable prediction of aqueous solubility with a simple neural network. As a comparison, we calculated the solubility of a test set of 258 compounds, ranging from simple hydrocarbons to more complex multifunctional organic molecules, with a commercial program (QMPR+ version 2.0.1 of SimulationPlus Inc.) and compared the results with predictions from our model. Statistical parameters indicate that for small and simple organic compounds, QMPR+ outperforms our model. However for more complex multifunctional molecules, our model is superior.

Drug Design↗
PubMedDate not supplied

Development of quantitative structure-property relationship models for early ADME evaluation in drug discovery. 2. Blood-brain barrier penetration.

A new molecular lipoaffinity descriptor was introduced in this paper to account for the effect of molecular hydrophobicity on blood-brain barrier penetration. The descriptor was defined based on Kier and Hall's atom-type electrotopological state indices. Its evaluation requires 2-D molecular bonding information only. A multiple linear regression equation using this descriptor and molecular weight reproduces the experimental logBB values of 55 training set compounds and 11 test set compounds satisfactorily with statistical parameters nearly identical to the best models based on polar surface area and ClogP. The results indicate that the lipoaffinity descriptor defined in this paper may be a significant descriptor for molecular transport properties across lipid bilayers.

Blood-Brain Barrier↗