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Biomedical subjects

R Y Lee

Publications and source records attributed to R Y Lee.

30 records · Page 2Linked to original sources
PubMed1996

The molecular genetics of retinoic acid receptors: cardiovascular and limb development.

The vitamin A metabolite retinoic acid (RA) is utilized as a signalling molecule in wide variety of developmental processes, defined by defects which occur after nutritional vitamin A deficiency or after exposure to excess vitamin A. We have initiated a genetic analysis of RA function through the establishment of lines of mice which carry germline mutations in the genes which encode retinoid receptors. Defects which result from developmental RA deficiency or excess have been recovered in embryos which are deficient in various combinations of retinoid receptors. In this chapter, our current understanding of the role of RA and retinoid receptors in cardiovascular and limb development are described, as for these our level of understanding is most advanced.

Animals↗
PubMed1995

Peptides which bind to E-selectin and block neutrophil adhesion.

E-selectin is an inducible cell adhesion molecule which mediates rolling of neutrophils on the endothelium, an early event in the development of an inflammatory response. Inhibition of selectin-mediated rolling is a possible means for controlling inflammation-induced diseases, and several classes of compounds have been tested for this use. We describe here the use of recombinant peptide library screening for identification and optimization of novel ligands which bind to E-selectin. Several of these peptides bind with Kd values in the low nanomolar range and block E-selectin-mediated adhesion of neutrophils in static and flow-cell assays. Administration of the peptide to mice undergoing an acute inflammatory response reduced the extent of neutrophil transmigration to the site of inflammation, demonstrating the utility of this compound as a potential therapeutic. The identification of a peptide ligand for E-selectin suggests that the complete natural ligand for this adhesion molecule may include protein as well as carbohydrate moieties.

Amino Acid Sequence↗
PubMed1995

Interacting genes required for pharyngeal excitation by motor neuron MC in Caenorhabditis elegans.

We studied the control of pharyngeal excitation in Caenorhabditis elegans. By laser ablating subsets of the pharyngeal nervous system, we found that the MC neuron type is necessary and probably sufficient for rapid pharyngeal pumping. Electropharyngeograms showed that MC transmits excitatory postsynaptic potentials, suggesting that MC acts as a neurogenic pacemaker for pharyngeal pumping. Mutations in genes required for acetylcholine (ACh) release and an antagonist of the nicotinic ACh receptor (nAChR) reduced pumping rates, suggesting that a nAChR is required for MC transmission. To identify genes required for MC neurotransmission, we screened for mutations that cause slow pumping but no other defects. Mutations in two genes, eat-2 and eat-18, eliminated MC neurotransmission. A gain-of-function eat-18 mutation, ad820sd, and a putative loss-of-function eat-18 mutation, ad1110, both reduced the excitation of pharyngeal muscle in response to the nAChR agonists nicotine and carbachol, suggesting that eat-18 is required for the function of a pharyngeal nAChR. Fourteen recessive mutations in eat-2 fell into five complementation classes. We found allele-specific genetic interactions between eat-2 and eat-18 that correlated with complementation classes of eat-2. We propose that eat-18 and eat-2 function in a multisubunit protein complex involved in the function of a pharyngeal nAChR.

Animals↗
PubMed1995

Mutations in the Caenorhabditis elegans Na,K-ATPase alpha-subunit gene, eat-6, disrupt excitable cell function.

We have cloned a Na,K-ATPase alpha-subunit gene from Caenorhabditis elegans and discovered that it is identical to the gene eat-6, eat-6 mutations cause feeble contractions and slow, delayed relaxations of pharyngeal muscle. The resting membrane potential of eat-6 mutant pharynxes is consistently depolarized compared to wild-type. The action potentials are smaller, and the return to resting potential is slower. To explain these abnormalities, we propose that a reduction of Na,K-ATPase activity in eat-6 mutants leads to a reduction of the ion concentration gradients that power membrane potential changes.

Amino Acid Sequence↗
PubMed1992

Intrarectal tear from water skiing.

We report a case of intrarectal tear and hemorrhage after a fall while water skiing. The injury resulted from rectal douche, or jet enema, which is dangerous because of the high pressure of the water jets forced into the rectum. The patient, a middle-aged woman, had colonoscopy, which revealed a deep rectal laceration. During subsequent colostomy, a full-thickness laceration and an extensive pelvic and retroperitoneal hematoma with some free blood were found. The patient's recovery was uneventful, and she subsequently had reanastomosis of her colostomy. We recommend protective apparel to prevent these injuries.

Accidental Falls↗
PubMed1990

Differential utilization of calcitonin gene regulatory DNA sequences in cultured lines of medullary thyroid carcinoma and small-cell lung carcinoma.

Regulation of expression of the human calcitonin gene was found to differ between two tumor lines of different tissue origin, medullary thyroid carcinoma (TT line) and small-cell lung carcinoma (DMS53 line). Distal 5' DNA elements between -750 and -2000 exhibited a stronger basal activity in DMS53 than in TT cells, whereas proximal DNA sequences between -132 and -252 mediated a dramatic cyclic AMP response in TT but not DMS53 cells.

Calcitonin↗
PubMed1989

Bacterial chitinase is modified and secreted in transgenic tobacco.

The chiA gene of Serratia marcescens codes for a secreted protein, bacterial chitinase (ChiA). We have investigated the modifications and the cellular location of ChiA when it is expressed in transgenic tobacco plants. Immunoblots on total leaf protein probed with antibody to ChiA showed that when the bacterial chitinase is expressed in plants, it migrates as a series of discrete bands with either the same or a slower mobility than the secreted bacterial protein. Analysis of the vacuum infiltrate of leaves expressing ChiA showed that the modified forms of the protein are enriched in the intercellular fluid. Media recovered from suspension cultures of cell lines expressing the chiA gene were also enriched for the modified forms of ChiA. Washed protoplasts, however, contained only the nonmodified form. The molecular weight of these polypeptides is reduced by treatment with glycopeptidase F but not with endoglycosidase H. Treatment of the suspension cultures with tunicamycin also leads to reduction in the molecular weight of the chitinase bands. We suggest that some of the ChiA protein is N-glycosylated and secreted when expressed in plants, and that the modifications are complex glycans. These results show that a bacterial signal sequence can function in plant cells, and that protein secretion from plant cells probably operates by a default pathway.

Journal Article↗
PubMed1988

Chronic intracerebroventricular CRF infusion attenuates ACTH-corticosterone release.

Bolus intracerebroventricular delivery of corticotropin-releasing factor (CRF) elicits acute responses of both the pituitary-adrenal axis and the sympathetic nervous system. We examined whether these stresslike responses could be maintained over a period of days by central delivery of CRF in nonstressed rats, as would be predicted if this peptide participates in the central nervous system regulation of chronic stress. CRF (4.3 or 21.5 micrograms/day) was continuously delivered into the cerebral ventricle via Alzet minipumps. In contrast to saline-infused controls, rats receiving CRF exhibited elevated excretions of corticosterone, norepinephrine, and urea nitrogen for several days. Thereafter, an attenuation of CRF responsiveness occurred when corticosterone excretion returned to basal levels despite continued central CRF infusion. However, CRF delivered intravenously during attenuation stimulated adrenocorticotropic hormone and corticosterone secretion, implicating a hypothalamic rather than pituitary locus for central CRF resistance. The present data do not permit a conclusion on whether the attenuation of the CRF response with time is the result of an ultrashort-loop negative-feedback mechanism or CRF receptor desensitization.

Adrenocorticotropic Hormone↗
PubMed1987

Characterization of Acetate and Pyruvate Metabolism in Suspension Cultures of Zea mays by C NMR Spectroscopy.

Carbon-13 nuclear magnetic resonance (NMR) spectroscopy has been applied to the direct observation of acetate and pyruvate metabolism in suspension cultures of Zea mays (var Black Mexican Sweet). Growth of the corn cells in the presence of 2 millimolar [2-(13)C]acetate resulted in a rapid uptake of the substrate from the medium and initial labeling (0-4 hours) of primarily the intracellular glutamate and malate pools. Further metabolism of these intermediates resulted in labeling of glutamine, aspartate, and alanine. With [1-(13)C]acetate as the substrate very little incorporation into intermediary metabolites was observed in the (13)C NMR spectra due to loss of the label as (13)CO(2). Uptake of [3-(13)C]pyruvate by the cells was considerably slower than with [2-(13)C]acetate; however, the labelling patterns were similar with the exception of increased [3-(13)C] alanine generation with pyruvate as the substrate. Growth of the cells for up to 96 hours with 2 millimolar [3-(13)C]pyruvate ultimately resulted in labeling of valine, leucine, isoleucine, threonine, and the polyamine putrescine.

Journal Article↗
PubMed1983

Stability of three oral liquid drug products repackaged in unit dose containers.

Stability of oral liquid forms of cimetidine hydrochloride, furosemide, and theophylline repackaged in polypropylene oral syringes and glass vials was assessed. Commercial preparations of each product were used; 2-ml quantities were placed in both types of container and stored at 4, 25, 44, 60, and 76 degrees C. Six samples from each container type at each temperature were tested at various times. Stability was defined as no greater than 10% loss of labeled potency. Assay was by high-performance liquid chromatography. All three drugs retained more than 90% of label claim in both types of containers after 180 days at 4 degrees C and 25 degrees C. For cimetidine hydrochloride and furosemide at these temperatures, there was no significant difference in concentration by container type; at the higher storage temperatures, the degradation rate in polypropylene syringes was significantly faster. For theophylline, loss of volume of 10% or greater occurred after 60 days at temperatures greater than 25 degrees C for both container types. Drug loss at higher temperatures was attributed to precipitation of theophylline out of the elixir rather than chemical degradation. Oral liquid cimetidine hydrochloride, furosemide, and theophylline repackaged in either polypropylene oral syringes or glass vials can be stored at 4 degrees C and 25 degrees C for 180 days with less than 10% loss of potency.

Cimetidine↗