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Biomedical subjects

K Lee

Publications and source records attributed to K Lee.

At least 955 records · Page 53Linked to original sources

Disposition of epirubicin in an oily contrast medium after intravenous and intrahepato-arterial administration in liver cancer: a preliminary report.

The present study reports findings on the disposition of epirubicin after an intrahepato-arterial administration of the Lipiodol-drug complex, prepared by mixing the drug-aqueous phase with the iodized oil by ultra-sonification, in 14 patients with histologically proven hepatoma or hepatomegaly with serum alpha-fetoprotein level above 500 micrograms.l-1. The volume of Lipiodol used was 5 ml and the epirubicin dose was 50 mg.m-2. Blood samples were obtained at various time intervals up to 72 h post-dose. Serum concentrations of epirubicin were measured by liquid chromatography with fluorometric detection. The area under serum concentration-time curve (AUCinfinity0) was higher in the Lipiodol-epirubicin group (n = 8) while the clearance was faster and elimination t1/2 and mean residence time shorter in the plain epirubicin group (n = 3). However, interindividual variation in metabolism of epirubicin would affect serum level of the drug. In three patients who were given intravenous and intrahepato-arterial injections (90 mg.m-2) of plain epirubicin and Lipiodol-drug complex, the relative bioavailability of Lipiodol-epirubicin complex (F = 0.76 and 0.45) was lower than that of plain epirubicin (F = 0.80 and 0.73) in two patients while it was approximately 100% (F = 1.06 and 1.20) in one patient. It is likely that liver function of the patients might be modified by the disease state over a period of 3 months in the cross-over study. Further studies with larger patient samples are required to confirm if there is a targeting effect of the Lipiodol-drug complex toward hepatoma using a better formulation of the drug in Lipiodol.

Adult↗

In situ localization of PTH/PTHrP receptor mRNA in the bone of fetal and young rats.

We characterized cells that express parathyroid hormone/parathyroid hormone related peptide (PTH/PTHrP) receptor mRNA in bones of fetal and postnatal rats by in situ hybridization. During endochondral development of fetal bones, PTH/PTHrP receptor transcripts were highly expressed both in maturing chondrocytes and in osteoblasts in the periosteum and ossification center, but not in fully hypertrophic chondrocytes. Similar to the localization in the fetal bones, PTH/PTHrP receptor mRNA expression was highly localized to maturing chondrocytes in the articular cartilage and growth plate, and to osteoblasts in the femur of young rats. In both young and fetal rats, transcripts for Type X collagen were localized to hypertrophic chondrocytes, mostly between chondrocytes and bone cells both of which express PTH/PTHrP receptor mRNA. Transcripts for PTH/PTHrP receptors and alkaline phosphatase co-localized in the bone of young rats, but they did not co-localize in fetal bones at the early stages of endochondral ossification. These results show that PTH/PTHrP receptor mRNA is expressed in a cell-type and stage-specific manner during skeletal development.

Animals↗

Use of the Comet assay to assess DNA damage in hemocytes and digestive gland cells of mussels and clams exposed to water contaminated with petroleum hydrocarbons.

Oil spills can result in the deposition of large quantities of petroleum hydrocarbons into intertidal and shallow waters seriously impacting bivalve populations. Petroleum hydrocarbons are enriched in polycyclic aromatic hydrocarbons (PAH) and PAH analogs many of which may have potential to damage DNA. The Comet assay is useful for assessing DNA damage and has been used to a limited degree with aquatic organisms, but mostly with studies in vitro. We have carried out studies with the Comet assay to assess the DNA damaging potential of complex mixtures of petroleum hydrocarbons for bivalves. Experiments were carried out with mussels (Mytilus edulis) and clams (Mya arenaria) with dispersions and water soluble fractions of an Arabian crude oil which was also chemically characterized in detail by GC-MS. Pilot studies were first conducted to evaluate test performance and reproducibility. An interindividual coefficient of variation ranging from 17 to 30% was established for the assay with hemocytes and digestive gland cells of both species. Exposure to hydrocarbon fractions had no significant impact on clams. However, an increase in DNA damage was observed at P < 0.1 with digestive gland cells of mussels exposed to aqueous fractions of a light crude oil. These studies have demonstrated a potential for DNA damage in bivalves exposed to oil spills in inshore waters as well as potential for interspecies sensitivity.

Animals↗

Comparison of infrared spectra of CLL cells with their ex vivo sensitivity (MTT assay) to chlorambucil and cladribine.

The drug resistance of leukemic cells from 21 patients with chronic lymphocytic leukemia (CLL) to the alkylating agent chlorambucil (CLB) and the nucleoside analog cladribine or 2-chlorodeoxyadenosine (CdA) was investigated by infrared spectroscopy. Drug sensitivities, determined in vitro with the tetrazolium dye (MTT) assay, were correlated with the infrared spectra of the CLL cells, applying linear discriminant analysis (LDA). The 63 spectra (three from each of the 21 samples), obtained before drug exposure, were successfully partitioned into drug-sensitive and drug-resistant groups; the LDA-based ex vivo prediction of the sensitivity to CdA or CLB was 85.7% and 80.3%, respectively. Similar changes in the composition/structure of DNA were observed between the spectra of the drug-sensitive and drug-resistant CLL cells for both CdA and CLB. However, CdA-resistant CLL cells could also be differentiated from CdA-sensitive CLL cells by spectral changes associated with membrane lipids; these differences were much less pronounced between CLB-resistant and CLB-sensitive CLL cells. We demonstrate here for the first time that infrared spectroscopy can be used as a new tool for predicting ex vivo drug response (sensitivity/resistance).

Adult↗

The fear of cloning.

Explore the source record for details and available documents.

Animals↗

The effects of lateral geniculate nucleus, area V4, and middle temporal (MT) lesions on visually guided eye movements.

Visually guided saccadic eye movements to singly presented stationary targets form a bimodal distribution. After superior colliculus lesions, the so called "express saccades" that form the first mode of the distribution are no longer obtained. The aim of this study was to determine what role several other neural systems play in the generation of express and regular saccades, with the latter being those that form the second mode in the bimodal distribution. Lesions were made in the parvocellular and magnocellular portions of the lateral geniculate nucleus to disrupt either the midget system or the parasol system that originates in the retina and areas V4 and MT. The effects of the lesions were examined on the accuracy and latency of saccadic eye movements made to stationary and to moving visual targets. Following magnocellular and MT lesions deficits were observed in smooth pursuit and in the amplitude of saccades made to moving targets. However, none of the lesions produced significant changes in the bimodal distribution of saccadic latencies to stationary targets. The results suggest that express saccades and regular saccades are not selectively mediated by either the midget or the parasol systems or by areas V4 and MT. Neither are the frontal eye fields involved as had previously been shown. We suggest that the superior colliculus plays a central role in producing both express and regular saccades by virtue of highly convergent input from numerous cortical structures.

Animals↗

Trauma history of sheltered battered women.

The purpose of this nursing research was to describe the trauma experience of sheltered battered women. Trauma history was operationalized as the participant's experience with traumatic life events in general (Trauma History Questionnaire [B. L. Green, 1995]) and with battering specifically (Conflict Tactics Scale, including a Physical Injury Severity scale). A convenience sample of 50 ethnically diverse women in the San Francisco Bay area was obtained from those residing in 2 shelters. Participants had experienced an average of 8.1 +/- 4.6 traumatic events (battering and nonbattering) over the course of their lives. Analysis of relationships between selected biopsychosocial and trauma history variables revealed the importance and beneficial effects of spiritual beliefs to many sheltered battered women.

Adolescent↗

New classes of fluorinated L-nucleosides; synthesis and antiviral activity.

The synthesis of 3'-fluorinated apionucleosides 7 and 2'-fluoro-2',3'-unsaturated L-nucleosides 8 via common synthon, 2-fluoro-butenolide 2, has been described. Among the newly synthesized nucleosides, L-2'-F-d4C, L-2'-F-d4FC and L-2'-F-d4A exhibit significant anti-HIV and anti-HBV activities.

Antiviral Agents↗

Ribose modified nucleosides and nucleotides as ligands for purine receptors.

Molecular modeling of receptors for adenosine and nucleotide (P2) receptors with docked ligand, based on mutagenesis, was carried out. Adenosine 3',5'-bisphosphate derivatives act as selective P2Y1 antagonists/partial agonists. The ribose moiety was replaced with carbocyclics, smaller and larger rings, conformationally constrained rings, and acyclics, producing compounds that retained receptor affinity. Conformational constraints were built into the ribose rings of nucleoside and nucleotide ligands using the methanocarba approach, i.e. fused cyclopropane and cyclopentane rings in place of ribose, suggesting a preference for the Northern (N) conformation among ligands for P2Y1 and A1 and A3ARs.

Animals↗