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Biomedical subjects

K W Cho

Publications and source records attributed to K W Cho.

At least 55 records · Page 3Linked to original sources

New acetylenic enol ethers of glycerol from the sponge Petrosia sp.

Ten acetylenic enol ethers of glycerols, including six new compounds (1-6) and a linear acetylenic alcohol (7), have been isolated from a sponge of the genus Petrosia. The structures of the novel compounds were elucidated by spectroscopic methods. The absolute stereochemistry of 1-7 was determined by chemical transformations and the Mosher method. Some of these compounds exhibited weak cytotoxicity against a human leukemia cell-line (K-562).

Acetylene↗

Modulation of endocardial natriuretic peptide receptors in right ventricular hypertrophy.

Natriuretic peptide (NP) receptors (NPRs) located at the endocardial endothelium are suggested to be involved in regulating myocardial contractility. However, the characteristics and modulation of NPRs in relation to cardiac failure are not well defined. This study examined the properties of NPRs in ventricular endocardium using quantitative receptor autoradiography, RT-PCR, Southern blot analysis, and activation of particulate guanylyl cyclase (GC) by NPs. In control rats, specific 125I-labeled rat atrial NP (rANP)(1-28) binding sites were localized in right (RV) and left ventricular (LV) endocardium. Binding affinities of 125I-rANP(1-28) were remarkably higher in RV than LV endocardium. Radioligand binding at these sites was mostly inhibited by des[Gln18,Ser19,Gly20,Leu21, Gly22]ANP(4-23), a specific NP clearance receptor ligand. mRNAs for all three recognized NPRs were detected in endocardial cells by RT-PCR and confirmed by Southern blot analysis. Production of cGMP by particulate GC in endocardial cell membranes was stimulated by NPs with a rank order of potency of C-type NP(1-22) >> brain NP (BNP)(1-26) > ANP(1-28). We also examined the modulation of these NPRs during cardiac hypertrophy induced by monocrotaline (MCT). In MCT-treated rats with pulmonary hypertension, specific (125)I-rANP(1-28) binding to hypertrophied RV endocardium almost disappeared and cGMP production by NPs was significantly decreased. In rats with pulmonary hypertension, plasma levels of ANP and BNP were increased by fivefold compared with controls. The results indicate that there is a differential distribution of NPRs in the cardiac chambers, with the most abundant binding sites in RV endocardium, that NPR-B is the predominant GC-coupled NPR in ventricular endocardium, and that endocardial NPRs are downregulated with ventricular hypertrophy. Downregulation of NPRs may be associated with an increment of endogenous NP production caused by mechanical overload in hypertrophied ventricle.

Animals↗

Involvement of the small GTPases XRhoA and XRnd1 in cell adhesion and head formation in early Xenopus development.

The Rho family of small GTPases regulates a variety of cellular functions, including the dynamics of the actin cytoskeleton, cell adhesion, transcription, cell growth and membrane trafficking. We have isolated the first Xenopus homologs of the Rho-like GTPases RhoA and Rnd1 and examined their potential roles in early Xenopus development. We found that Xenopus Rnd1 (XRnd1) is expressed in tissues undergoing extensive morphogenetic changes, such as marginal zone cells involuting through the blastopore, somitogenic mesoderm during somite formation and neural crest cells. XRnd1 also causes a severe loss of cell adhesion in overexpression experiments. These data and the expression pattern suggest that XRnd1 regulates morphogenetic movements by modulating cell adhesion in early embryos. Xenopus RhoA (XRhoA) is a potential XRnd1 antagonist, since overexpression of XRhoA increases cell adhesion in the embryo and reverses the disruption of cell adhesion caused by XRnd1. In addition to the potential roles of XRnd1 and XRhoA in the regulation of cell adhesion, we find a role for XRhoA in axis formation. When coinjected with dominant-negative BMP receptor (tBR) in the ventral side of the embryo, XRhoA causes the formation of head structures resembling the phenotype seen after coinjection of wnt inhibitors with dominant-negative BMP receptor. Since dominant-negative XRhoA is able to reduce the formation of head structures, we propose that XRhoA activity is essential for head formation. Thus, XRhoA may have a dual role in the embryo by regulating cell adhesion properties and pattern formation.

Amino Acid Sequence↗

An AI approach to dynamic visual field testing.

Visual field test results are crucial to the accuracy and efficiency of diagnosing blinding diseases such as glaucoma. Herein, a method of integrating self-organizing neural networks and empirical heuristics is used to perform visual field tests via a dynamic test strategy, which can lead to a reduction in the number of trials in a perimetric test. Experiments performed using clinical test records show that we are able to reduce by 20% to 30% the number of trials per test without much adverse effect on the accuracy of the tests.

Algorithms↗

Localization of atrial natriuretic peptide receptors in the rat tongue and hard palate.

Atrial natriuretic peptide (ANP) receptors were characterized in rat oral mucosa using quantitative in vitro autoradiography and activation of particulate guanylyl cyclase (GC) by natriuretic peptides. Competition-binding analysis performed by quantitative in vitro autoradiography demonstrated specific [125I]rANP(1-28) binding sites in the tongue and hard palate. The precise location of this binding was revealed on the basal and parabasal cells of the epithelia by microautoradiography. The dissociation constant (Kd) and maximal binding capacity (Bmax) of these sites were 3.34+/-1.35 nM and 2.71+/-2.21 fmol/mm2 on the epithelium of the tongue, and 4.09+/-1.52 nM and 3.45+/-3.01 fmol/mm2 on the epithelium of the hard palate, respectively. Receptor subtypes were characterized by competition with des [Gln18, Ser19, Gly20, Leu21, Gly22] ANP(4-23) (C-ANP), a specific ligand for the clearance receptor (NPR-C). These binding sites were displaced by C-ANP with inhibition constant (Ki) of 8.96+/-3.18 nM and Bmax of 2.89+/-2.45 fmol/mm2 on the epithelium of the tongue, and Ki of 9.12+/-2.71 nM and Bmax of 3.08+/-2.94 fmol/mm2 on the epithelium of the hard palate, respectively. Production of cyclic GMP by particulate GC in the epithelial membranes of the tongue and hard palate was stimulated by rANP(1-28), porcine brain natriuretic peptide (BNP)(1-26), and C-type natriuretic peptide (CNP)(1-22) in a dose-dependent manner. These results indicate that ANP-binding sites in the epithelium of the tongue and hard palate are mainly clearance receptors (NPR-C) but biological receptors (NPR-A and/or NPR-B) with GC activity are also present, and suggest that ANP may have a role in the proliferation of the oral epithelial cells, especially in the tongue and hard palate.

Analysis of Variance↗

Clinicopathological and immunological characteristics of six cats with granular lymphocyte tumors.

Clinical and immunological characteristics were investigated in six cases of feline granular lymphocyte (GL) tumor. The ages of the affected cats were relatively old, ranging from 4 to 13 years of age. Gastrointestinal signs were commonly observed in these cases. Only one of the six GL tumor cases was positive for feline leukemia virus (FeLV) antigen. Phenotypic analysis revealed that the GL tumor cells from all of the six cases lacked the T- or B-cell markers. These GL tumor cells were examined by Southern blot analysis using feline immunoglobulin (Ig) and T-cell receptor (TCR) gene probes. GL tumor cells obtained from two cases were identified as cells of T-cell lineage by the presence of a rearranged TCR beta gene, whereas those from the other four cases were considered to be derived from non-T- non-B-cell lineage because of the absence of rearrangement of these genes. These findings indicated that feline GL tumors can be considered as a specific disease entity in feline lymphomas because the cases examined in this study showed onset at an older age, a low incidence of FeLV infection and frequent involvement of gastrointestinal lesions, which are not found in typical FeLV-associated lymphomas. Although no specific phenotypes was observed by phenotypic analysis, the feline GL tumor cells were divided into two consistent genotypes of T-cell or non-T- non-B-cell lineages.

Abdominal Neoplasms↗

New secosteroids from a gorgonian of the genus Muricella.

Calicoferols F-I (2-5), four new 9,10-secosteroids, have been isolated from a gorgonian of the genus Muricella collected from Jaeju Island, Korea. The structures of these compounds have been determined by combined spectroscopic methods. Calicoferols exhibited significant cytotoxicity and inhibitory activity against PLA2.

Animals↗

Presence and biological activity of C-type natriuretic peptide-dependent guanylate cyclase-coupled receptor in the penile corpus cavernosum.

PURPOSE: To investigate the presence of C-type natriuretic peptide 1-22 (CNP)-dependent guanylyl cyclase (GC)-coupled receptor and its biological function in the penile erectile smooth muscle. MATERIALS AND METHODS: Experiments have been done in rabbit and rat to detect cyclic GMP (cGMP) generation by the activation of particulate GC by natriuretic peptides (NPs) in cavernosal membrane, to localize precise receptor using a quantitative in vitro autoradiography of the snap frozen sections, to define natriuretic peptide receptor (NPR) mRNA using a reverse transcriptase-polymerase chain reaction (RT-PCR) technique and to monitor changes of erectile smooth muscle tone by NPs in the penile tissue strips. RESULTS: Productions of cGMP by particulate GC in the corpus cavernosum membranes of rabbit and rat were stimulated by CNP, atrial natriuretic peptide 1-28 (ANP) and brain natriuretic peptide 1-26 (BNP) with a rank order of potency of CNP > BNP > ANP. HS-142-1, a selective antagonist for the GC-coupled NPR, inhibited the CNP-stimulated cGMP production in corpus cavernosal membrane of rabbit and rat. Specific 125I-(Tyr[0])-CNP bindings were localized in the corpus cavernosal smooth muscle of rabbit with Kd of 19.92+/-3.38 nM. and Bmax of 734.64+/-139.63 amol./mm2. B-subtype of NPR mRNA was detected in the penile corpus cavernosum of rat using RT-PCR technique. CNP relaxed the smooth muscle contracted by Nomega-nitro-L-arginine methylester (L-NAME). CONCLUSIONS: These results suggest for the first time that CNP modulates the erectile smooth muscle tone of penis by predominant activation of B-subtype of NPR with augmentation of cGMP production via particulate GC.

Animals↗

Production of a DPP activity gradient in the early Drosophila embryo through the opposing actions of the SOG and TLD proteins.

During early Drosophila embryogenesis, several zygotic gene products act to establish a posttranscriptional activity gradient of the morphogen DPP. Among these molecules, Tolloid, a putative metalloprotease related to BMP-1, enhances DPP function, while SOG, an ortholog of the Xenopus organizer Chordin, inhibits DPP function. Using epistasis tests and a Xenopus secondary axis induction assay, we show that TLD negates the inhibitory effects of SOG/CHD on DPP/BMP-type ligands. In transient transfection assays, we demonstrate that TLD cleaves SOG and that cleavage is stimulated by DPP. We propose that formation of the embryonic DPP activity gradient involves the opposing effects of SOG inhibiting DPP and TLD processing SOG to release DPP from the inhibitory complex.

Animals↗

Cloning and chromosome mapping of the feline genes p21WAF1 and p27Kip1.

For investigation of the relation of cell cycle regulation with tumorigenesis in cats, we carried out molecular cloning of feline p21WAF1 and p27Kip1 cDNAs and chromosomal mapping of these genes on the cat genome. The feline p21WAF1 cDNA clone obtained in this study encoded 164 amino acids (aa) showing 83.5% and 76.8% sequence similarity with those of the human and mouse counterparts, respectively. The cat p27Kip1 cDNA clone isolated here encoded 198 aa, showing sequence similarities of 93.4% and 90.4% with its human and mouse counterparts, respectively. Using a panel of feline x rodent somatic cell hybrids, the feline CDKN1A (p21WAF1) and CDKN1B (p27Kip1) loci were assigned to feline chromosomes B2 and B4, respectively. Southern-blot analyses of 17 feline spontaneous leukemia and lymphoma cases using these cDNAs as probes did not reveal any rearrangements in either the p21WAF1 or the p27Kip1 gene. RT-PCR/SSCP (single strand conformation polymorphism) analysis of p27Kip1 cDNA did not uncover any amino acid substitutions in the 10 feline leukemia and lymphoma cases that were examined.

Amino Acid Sequence↗

Overlapping distribution of receptors for atrial natriuretic peptide and angiotensin II in the kidney and the adrenal gland of the freshwater turtle, Amyda japonica.

The distribution of receptors for atrial natriuretic peptide (ANP) and angiotensin II (ANG II) in the kidney and adrenal gland of the freshwater turtle, Amyda japonica, was examined by quantitative in vitro autoradiography using 125I-labeled rat (r)ANP1-28 and 125I-labeled human ANG II as labeled ligands. Receptor subtypes were characterized by competition with des[Gln18,Ser19,Gly20, Leu21, Gly22] ANP(4-23) (C-ANP) as a selective ligand of the clearance receptors to specific 125I-rANP(1-28) binding, and with DuP 753 and PD 123319 as nonpeptide antagonists for ANG II receptors type 1 (AT1) and type 2 (AT2) subtypes, respectively, to 125I-ANG II binding. Specific 125I-rANP(1-28) binding with a single binding site was found overlying glomeruli of the kidney and the outer zone of the adrenal gland with dissociation constants (Kd) of 4.39 +/- 0.33 and 6.07 +/- 1.36 nM, respectively. C-ANP (10 microM) inhibited about 90% of the glomerular and adrenal 125I-rANP(1-28) binding. Specific 125I-ANG II binding was also localized in the glomeruli of the kidney and the outer zone of the adrenal gland with Kd of 1.02 +/- 0.22 and 0.37 +/- 0.04 nM, respectively. DuP 753 (10 microM) potently inhibited about 80% of glomerular and 90% of adrenal 125I-ANG II binding, whereas PD 123319 (10 microM) was very weak in competing for specific 125I-ANG II binding in both tissues. Therefore, these results indicate that specific ANP and ANG II receptors with high affinities have an overlapping distribution in glomeruli of the kidney and the outer zone of the adrenal gland of the freshwater turtle. They also suggest that biological and clearance ANP receptor-like subtypes coexist in both tissues, and the predominant ANG II receptor subtype in these tissues is the AT1-like receptor. The overlapping distribution of specific receptors for both peptides in these tissues provides the basis for possible receptor interactions to exert a functional antagonism between ANP and ANG II in the freshwater turtle.

Adrenal Glands↗

Glibenclamide suppresses stretch-activated ANP secretion: involvements of K+ATP channels and L-type Ca2+ channel modulation.

The mechanism by which glibenclamide regulates mechanically activated atrial natriuretic peptide (ANP) secretion was investigated using isolated perfused rat atria. A reduction in atrial pressure from an experimentally imposed distending pressure stimulated the secretion of ANP and caused concomitant translocation of extracellular fluid (ECF) into the atrial lumen. The activation of ANP secretion and ECF translocation were closely correlated with atrial volume changes and the increase in ANP secretion was a function of the ECF translocation. Glibenclamide (1, 10, 100 microM), an ATP-sensitive K+ (K+ATP) channel blocker, had no effect on the basal secretion of ANP, suppressed the stimulation of stretch-activated ANP secretion in a dose-dependent manner, but not the translocation of the ECF. Glipizide (100 microM) and tolbutamide (100 microM), other K+ATP channel blockers, had similar effects to those of glibenclamide. Suppression by glibenclamide (100 microM) of the stretch-induced ANP secretion was not observed in atria that had been pretreated with pinacidil (200 microM), an ATP-sensitive K+ channel opener: pinacidil alone had no effect on ECF translocation and ANP secretion. Furthermore, blocking Ca2+ influx by using the Ca2+ channel blocker diltiazem (10 nM), or a Ca2+-depleted medium prevented the suppression of stretch-induced ANP secretion by glibenclamide. In other experiments, atrial distension produced a slight membrane depolarization of cardiomyocytes; this was accentuated in the presence of glibenclamide. Furthermore, in single cardiomyocytes, glibenclamide increased the intracellular Ca2+ concentration ([Ca2+]i) in a dose-dependent manner. From these results, we suggest that glibenclamide suppresses atrial release of ANP by blocking K+ATP channels and increasing Ca2+ influx and that the K+ATP channels are associated with the regulation of the mechanically activated ANP secretion from the atria.

Adenosine Triphosphate↗

Genomic structure of the bovine mb-1 gene encoding the Ig-alpha subunit of the B cell antigen receptor complex.

The B cell antigen receptor, (BCR) comprises surface immunoglobulin and disulfide-bonded heterodimer of Ig-alpha and Ig-beta chains, which are the products of the mb-1 and B29 genes, respectively. In this study, we describe the isolation and analysis of a 6.2-kb genomic DNA clone containing bovine mb-1 gene encoding Ig-alpha. Sequence data revealed that the bovine mb-1 gene is composed of five exons and four introns, and that its overall structure is very similar to those of murine and human genes. The 5' upstream region of the bovine mb-1 gene contained potential protein binding motifs of transcription factors including EBF, Sp1, NF-kappa B, MUF/Ets-1 and AP 2. As with the murine and human mb-1 genes, the 5' region of the bovine mb-1 gene lacked a TATA box. The present study will be useful for understanding the regulated expression of the bovine mb-1 gene at different stages of development and activation as well as in bovine leukemia virus infection.

Amino Acid Sequence↗