PubMed Health⌕ Search

Biomedical subjects

Y Lee

Publications and source records attributed to Y Lee.

At least 19 recordsLinked to original sources
PubMed1997

Leptin normalizes the impaired response of proinsulin mRNA to long chain fatty acids in heterozygous Zucker diabetic fatty rats.

To determine if underleptinization of islets of Zucker diabetic fatty (ZDF) rats is the proximal cause of their inability to compensate for obesity, we compared the proinsulin/beta-actin mRNA ratio in heterozygous (fa/+) ZDF rats with that of wild-type (+/+) and homozygous (fa/fa) ZDF rats. In +/+ islets cultured with 2 mM free fatty acids (FFA) the proinsulin mRNA ratio rose 2.4-fold at 12 h. In fa/+ islets, the ratio rose only 65% above normal. There was no change in fa/fa islets. The presence of leptin (20 ng/ml) in the culture medium increased the FFA-induced response of proinsulin mRNA of fa/+ islets to that of +/+ islets while reducing FFA incorporation into triglycerides. The leptin-induced improvement in the proinsulin mRNA response was independent of any changes in glucose usage. These findings support a causal relationship between diminished leptin action on islets and the impaired beta-cell response to FFA in ZDF rats.

Actins↗
PubMed1997

Detection of a dup(17q) and inv(16) by fluorescence in situ hybridization in acute myelomonocytic leukemia.

Two cases of acute myelomonocytic leukemia (AMMoL) of FAB type M4Eo are described in which a primary subclone containing a dup(17)(q21q25) and a subclone containing dup(17)(q21q25), inv(16)(p13q22) were seen in one patient, and -7, dup(17)(q21q25) in another. Fluorescence in situ hybridization (FISH) was carried out for the confirmation of the duplicated segment and breakpoint of inv(16). Inv(16) is a well known anomaly in AMMoL, whereas dup(17q) is rare though as not yet confirmed, this anomaly could be a nonrandom or novel change in AMMoL.

Child↗
PubMed1997

Leptin- or troglitazone-induced lipopenia protects islets from interleukin 1beta cytotoxicity.

Interleukin 1beta (IL-1beta)-induced beta cell cytotoxicity has been implicated in the autoimmune cytotoxicity of insulin-dependent diabetes mellitus. These cytotoxic effects may be mediated by nitric oxide (NO). Since long-chain fatty acids (FFA), like IL-1beta, upregulate inducible nitric oxide synthase and enhance NO generation in islets, it seemed possible that islets might be protected from IL-1beta-induced damage by lowering their lipid content. We found that IL-1beta-induced NO production varied directly and islet cell viability inversely with islet triglyceride (TG) content. Fat-laden islets of obese rats were most vulnerable to IL-1beta, while moderately fat-depleted islets of food-restricted normal rats were less vulnerable than those of free-feeding normal rats. Severely lipopenic islets of rats made chronically hyperleptinemic by adenoviral leptin gene transfer resisted IL-1beta cytotoxicity even at 300 pg/ml, the maximal concentration. Troglitazone lowered islet TG in cultured islets from both normal rats and obese, leptin-resistant rats and reduced NO production and enhanced cell survival. We conclude that measures that lower islet TG content protect against IL-1beta-induced NO production and cytotoxicity. Leptin or troglitazone could provide in vivo protection against insulin-dependent diabetes mellitus.

Animals↗
PubMed1997

The binding of two dimers of IciA protein to the dnaA promoter 1P element enhances the binding of RNA polymerase to the dnaA promoter 1P.

Transcription of the dnaA gene from the promoter 1P has been shown to be activated in vitro and in vivo by the binding of IciA protein to two sites on the dnaA promoter region [Lee, Y. S., Kim, H., and Hwang, D. S. (1996) Mol. Microbiol . 19, 389-396; Lee, Y. S., and Hwang, D. S. (1997) J. Biol. Chem. 272, 83-88]. In vitro transcription assays using DNA fragments carrying variable combinations of two IciA binding sites revealed that IciA binding site I (IciA I site), which is located upstream of the promoter 1P, is responsible for the transcriptional activation. Binding of one dimeric IciA protein to the IciA I site is followed by binding of the second dimer. Two dimers of IciA protein, rather than one dimer, on the IciA I site appeared to enhance the binding of RNA polymerase to the promoter 1P, resulting in the activation of transcription from the promoter 1P.

Bacterial Proteins↗
PubMed1997

Diversity among clinical isolates of Helicobacter pylori in Korea.

Eleven strains of Helicobacter pylori were isolated from biopsy specimens obtained at the A-San Medical Center from December, 1995 to February, 1996. Every H. pylori positive patient was diagnosed to have chronic, erosive, or mild superficial gastritis. To determine the diversity in clinical isolates, the following were studied: total protein profile, plasmid profile, presence of cagA, and variation in DNA sequence. Protein profiles of nine isolates were similar to each other while two isolates had a 35 kDa protein which did not appear in others. The presence of cagA was detected with PCR in seven isolates (63%). Among eleven isolates, seven (63%) carried plasmids. Each isolate showed a big diversity with a PCR-based randomly amplified polymorphic DNA method. Even though all H. pylori isolates used in this study were isolated from gastritis patients at the same hospital, their molecular and biological characteristics were quite different from another showing a big diversity in H. pylori.

Antigens, Bacterial↗
PubMed1997

Cloning and expression of a cDNA encoding a novel protein serine/threonine kinase predominantly expressed in hematopoietic cells.

We have isolated a cDNA clone of a new member of protein serine/threonine kinases, MPK38, from a cDNA library constructed from the murine teratocarcinoma PCC4 cell line by the polymerase chain reaction. MPK38 was transcribed as an approx. 2.5 kb mRNA encoding for a protein of 643 amino acids. N-terminus of MPK38 contains the kinase catalytic domain which exhibits approximately 60% protein sequence identity with the SNF1 serine/threonine kinase family. The MPK38 cDNA directs the in vitro translation of two protein species of approx. 70 and approx. 50 kDa, which appear to result from an internal initiation of translation. MPK38 was predominantly expressed in thymus and spleen, but was not detectable in kidney, liver, and muscle in the adult tissues. In addition, MPK38 was apparently expressed in T lineage cells and a macrophage/monocyte cell, but was not detectable in a B cell line and an embryonic cell line. However, a low level of MPK38 transcript was detectable in a mast cell line after a longer exposure. Furthermore, MPK38 gene product showed the kinase activity which was assessed by immune complex kinase assay. Thus, MPK38 gene product seems to play an important role in signal transduction of certain lineages of hematopoietic cells.

Amino Acid Sequence↗
PubMed1997

Induction of uncoupling protein-2 mRNA by troglitazone in the pancreatic islets of Zucker diabetic fatty rats.

Because troglitazone, like leptin, lowers the triglyceride (TG) content of pancreatic islets, we searched for other leptinomimetic actions. Leptin upregulates the expression of uncoupling protein-2 (UCP-2) mRNA in islets of normal rats, but has no effect in islets of obese Zucker Diabetic Fatty (ZDF) rats with mutated leptin receptors. We report here that troglitazone also increases the UCP-2/beta-actin mRNA ratio by 115% in wild type ZDF rats and by 400% in obese ZDF rats.

Animals↗
PubMed1997

Role of the septum in the excitatory effect of corticotropin-releasing hormone on the acoustic startle reflex.

Intracerebroventricular administration of corticotropin-releasing hormone (CRH) elicits a constellation of behavioral, autonomic, and endocrinological changes typically observed in stress. One of the behavioral changes after intracerebroventricular CRH is a profound increase of startle amplitude (CRH-enhanced startle). The present study examined the role of the septum in CRH-enhanced startle. The septum has direct and indirect connections to the amygdala and inhibits the amygdala. Electrophysiological data show that CRH in the septum is inhibitory. Therefore, it has been hypothesized that intracerebroventricular CRH inhibits the septum, which in turn disinhibits the amygdala, resulting in a constellation of changes via activation of amygdala efferent targets. In testing this hypothesis, it was found that electrolytic lesions of the medial septum, but not the lateral septum, blocked CRH-enhanced startle. However, fiber-sparing chemical lesions of the medial septum did not block CRH-enhanced startle, suggesting that the blockade seen with the electrolytic lesions was caused by damage to fibers of passage. A major fiber bundle passing through the medial septum is the fornix, the primary efferent pathway for the hippocampus. Fimbria transection blocked CRH-enhanced startle almost completely, whereas the large electrolytic lesions of the dorsal hippocampus did not block CRH-enhanced startle. Taken together, these data suggest that perhaps the ventral hippocampus and its efferent target areas, which communicate via the fimbria, may be critically involved in CRH-enhanced startle.

Acoustic Stimulation↗
PubMed1997

Role of the hippocampus, the bed nucleus of the stria terminalis, and the amygdala in the excitatory effect of corticotropin-releasing hormone on the acoustic startle reflex.

Previously, we demonstrated that transection of the fimbria/fornix blocked the excitatory effect of corticotropin-releasing hormone (CRH) on startle (CRH-enhanced startle), suggesting that the hippocampus and its efferent target areas that communicate via the fimbria may be critically involved in CRH-enhanced startle. The bed nucleus of the stria terminalis (BNST) receives direct projections from the ventral hippocampus via the fimbria/fornix. Therefore, the role of the ventral hippocampus, the BNST, and the amygdala in CRH-enhanced startle was investigated. NMDA lesions of the BNST completely blocked CRH-enhanced startle, whereas chemical lesions of the ventral hippocampus and the amygdala failed to block CRH-enhanced startle. However, the same amygdala-lesioned animals showed a complete blockade of fear-potentiated startle, a conditioned fear response sensitive to manipulations of the amygdala. In contrast, BNST-lesioned rats had normal fear-potentiated startle. This indicates a double dissociation between the BNST and the amygdala in two different paradigms that enhance startle amplitude. Microinfusions of CRH into the BNST, but not into the ventral hippocampus, mimicked intracerebroventricular CRH effects. Furthermore, infusion of a CRH antagonist into the BNST blocked CRH-enhanced startle in a dose-dependent manner. Control studies showed that this blockade did not result from either leakage of the antagonist into the ventricular system or a local anesthetic effect caused by infusion of the antagonist into the BNST. The present studies strongly suggest that CRH in the CSF can activate the BNST, which could lead to activation of brainstem and hypothalamic BNST target areas involved in anxiety and stress responses.

Acoustic Stimulation↗
PubMed1997

Inhibition of mouse thymidylate synthase promoter activity by the wild-type p53 tumor suppressor protein.

The p53 tumor suppressor protein is an important negative regulator of the G1 to S transition in mammalian cells. We have investigated the effect of p53 on the expression of the mouse thymidylate synthase (TS) gene, which normally increases as cells enter S phase. A luciferase indicator gene that was driven by the wild-type or various modified forms of the TATA-less mouse TS promoter was transiently cotransfected with a p53 expression plasmid into TS-deficient hamster V79 cells and the level of luciferase activity was determined. We found that wild-type p53 inhibited TS promoter activity by greater than 95% but had a strong stimulatory effect on an artificial promoter that contained multiple p53-binding sites. In contrast, an expression plasmid that encodes a mutant form of p53 or a wild-type retinoblastoma tumor suppressor protein had little effect on TS promoter activity. Deletion of sequences upstream or downstream of the TS essential promoter region, or inactivation of each of the known elements within the essential promoter region, had no effect on the ability of wild-type p53 to inhibit TS promoter activity. Our observations indicate that the inhibition of TS promoter activity by p53 is not due to the presence of a specific p53 negative response element in the TS promoter. Rather, it appears that p53 inhibits the TS promoter by sequestering ("squelching") one or more general transcription factors.

Animals↗
PubMed1997

Role of nitric oxide in obesity-induced beta cell disease.

Here we report that free fatty acid-induced suppression of insulin output in prediabetic Zucker diabetic fatty (ZDF) rats is mediated by NO. When normal islets were cultured in 2 mM FFA, NO production and basal insulin secretion increased slightly. In cultured prediabetic ZDF islets, FFA induced a fourfold greater rise in NO, upregulated mRNA of inducible nitric oxide synthase (iNOS), and reduced insulin output; both nicotinamide and aminoguanidine, which lower NO, prevented the FFA-mediated increase in iNOS mRNA, reduced NO, and minimized the loss of insulin secretion. In vivo nicotinamide or aminoguanidine treatment of prediabetic ZDF rats prevented the iNOS expression in islets and decreased beta cell dysfunction while blocking beta cell destruction and hyperglycemia. We conclude that NO-lowering agents prevent adipogenic diabetes in obese rats.

Animals↗
PubMed1997

In vivo analyses of upstream promoter sequence elements in the 5 S rRNA gene from Saccharomyces cerevisiae.

Upstream promoter elements of the Saccharomyces cerevisiae 5 S rRNA gene have been characterized by genomic DNase I "footprinting" and by in vivo mutational analyses using base substitutions and deletions. A high copy shuttle-vector was used to efficiently express the mutant 5 S rRNA genes in vivo and a structural mutation in the 5 S rRNA, which was previously shown to be functionally neutral but easily detected by gel electrophoresis, allowed for an accurate measure of gene expression. The results provide direct evidence for upstream regulatory elements which confirms a start site element (sse) from -1 to -8 and identifies a new independent upstream promoter element (upe) centered from about -17 to -20. In contrast to previous reports with reconstituted systems, both elements dramatically affect the efficiency of gene expression and suggest that the saturated conditions which are used in reconstituted studies mask sequence dependence; a dependency that could be physiologically significant and play a role in the regulation of 5 S rRNA expression. The footprint analyses support an extended region of protein interaction as recently observed in reconstituted systems but again provide evidence of significant structural rearrangements when the upstream sequence is changed.

Base Sequence↗
PubMed1997

Bcl-2 does not protect Burkitt's lymphoma cells from oxidant-induced cell death.

Bcl-2 is an oncogene that confers deregulated growth potential to B lymphocytes through its ability to inhibit apoptotic cell death. A specific molecular activity for the Bcl-2 protein has not been identified, but several lines of evidence have supported a role in protection of cells from oxidative stress. We investigated whether there is a correlation between expression of high levels of Bcl-2 and susceptibility of human Burkitt's lymphoma cell lines to H2O2-induced killing. The amount of H2O2 required to kill 50% of cells in 24 hours varied widely in the seven different lymphoma cell lines that were tested, ranging from 35 to 500 micromol/L H2O2. However, expression of high levels of endogenous Bcl-2 did not protect the cells from H2O2-induced killing, even though it was effective in protecting the cells from apoptosis induced by agents such as A23187. Thus, Bcl-2 was functional in preventing apoptosis but did not act in an antioxidant capacity. The results were confirmed using a Burkitt's lymphoma cell line overexpressing transfected bcl-2. The results may be explained by the observation that H2O2 was inefficient at inducing apoptosis in these mature B-cell lines. Nonapoptotic death induced by H2O2 was not prevented by Bcl-2.

Apoptosis↗
PubMed1997

Ribosomal 5 S rRNA maturation in Saccharomyces cerevisiae.

The maturation of the ribosomal 5 S RNA in Saccharomyces cerevisiae is examined based on the expression of mutant 5 S rRNA genes, in vivo, and a parallel analysis of RNA processing, in vitro. Both types of analysis indicate that 5 S rRNA processing is not dependent on the nucleotide sequence of either the external transcribed spacer or the mature 5 S rRNA. The results further indicate the RNA is processed by an exonuclease activity which is limited primarily or entirely by helix I, the secondary structure formed between the mature and interacting termini. The 5 S RNA binding protein (YL3) also appears not to influence directly the maturation process, but rather to play a role in protecting the rRNA from further degradation by "housekeeping" nucleases. Taken together, the results continue to support a "quality control" function which helps to ensure that during maturation only normal precursors are processed and assembled into active ribosomes.

Nucleic Acid Conformation↗
PubMed1997

Induction by leptin of uncoupling protein-2 and enzymes of fatty acid oxidation.

We have studied mechanisms by which leptin overexpression, which reduces body weight via anorexic and thermogenic actions, induces triglyceride depletion in adipocytes and nonadipocytes. Here we show that leptin alters in pancreatic islets the mRNA of the genes encoding enzymes of free fatty acid metabolism and uncoupling protein-2 (UCP-2). In animals infused with a recombinant adenovirus containing the leptin cDNA, the levels of mRNAs encoding enzymes of mitochondrial and peroxisomal oxidation rose 2- to 3-fold, whereas mRNA encoding an enzyme of esterification declined in islets from hyperleptinemic rats. Islet UCP-2 mRNA rose 6-fold. All in vivo changes occurred in vitro in normal islets cultured with recombinant leptin, indicating direct extraneural effects. Leptin overexpression increased UCP-2 mRNA by more than 10-fold in epididymal, retroperitoneal, and subcutaneous fat tissue of normal, but not of leptin-receptor-defective obese rats. By directly regulating the expression of enzymes of free fatty acid metabolism and of UCP-2, leptin controls intracellular triglyceride content of certain nonadipocytes, as well as adipocytes.

Adipocytes↗
PubMed1997

Serotonin1A receptor agonists induce Fos protein expression in the locus coeruleus of the conscious rat.

The azapirones, which are partial agonists of the serotonin (5-HT)1A receptor, possess anxiolytic activity. These agents may act at the pre- or postsynaptic 5-HT1A receptors, and involve the noradrenergic system. To determine whether these drugs activate noradrenergic neurons via 5-HT1A receptors, we have evaluated the expression of the immediate early gene c-fos in the locus coeruleus. Tandospirone and ipsapirone each induced expression of Fos protein in the noradrenergic neurons of the locus coeruleus of conscious rats. This effect was reversed by pretreatment with (+)-WAY100135, a specific 5-HT1A antagonist. These results clearly demonstrate that azapirones activate noradrenergic neurons via 5-HT1A receptors.

Animals↗
PubMed1997

Function of the repeated sequence in the 3' flanking region of the Escherichia coli rnpB gene on transcription termination and RNA processing.

The 3' flanking region of the Escherichia coli rnpB gene-encoding M1 RNA, the RNA component of RNase P, contains a 113 bp repeated sequence. This sequence, successively reiterating 3.5 times, includes the region for intrinsic termination. In vivo termination of transcription occurs mostly at the first terminator (T1). Analysis of deletions at the 3' flanking region revealed that the second terminator (T2) and third (T3) are functional in vivo and that the sequences preceding the region coding for an RNA-terminator hairpin and U-rich 3' tail are essential for efficient termination. Transcripts terminating at T2 and T3 were also processed at the 3' end in a manner similar to those terminating at T1.

Base Sequence↗