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Biomedical subjects

D J Choi

Publications and source records attributed to D J Choi.

18 recordsLinked to original sources
PubMed2005

Prognostic significance of glycaemic control in patients with HBV and HCV-related cirrhosis and diabetes mellitus.

AIMS: Diabetes mellitus (DM) is frequently observed in patients with cirrhosis, particularly that due to hepatitis C virus (HCV) infection. However, no studies have focused on the clinical significance of glycaemic control in cirrhotic patients because of their short life expectancy and poor hepatic function. The aim of this study was to evaluate the prognostic impact of glycaemic control in patients with hepatitis B virus (HBV) and HCV-related cirrhosis and DM. METHODS: A total of 434 patients with HCV-related (HCV group, n = 88) or HBV-related (HBV group, n = 346) cirrhosis were studied retrospectively. We determined the prevalence of DM and treatment methods for hyperglycaemia and status of glycaemic control, and the patients' outcome. RESULTS: The prevalence of DM was 43.2% (38/88) in the HCV group and 19.7% (68/346) in the HBV group. Patients in the HCV group were older with a female preponderance. DM was detected before the diagnosis of cirrhosis or simultaneously in 92% and 79% in the HCV and HBV groups, respectively. Most patients were treated with insulin or oral hypoglycaemic agents. However, blood glucose levels were maintained within the normal range in 34.2% of the HCV group and in 23.5% of the HBV group. Forty-six patients died during the observation period in both groups. Hepatic failure was the most common cause of death, and sepsis and variceal bleeding were more frequent in the HCV group than in the HBV group. Multivariate analysis showed that Child-Pugh class was the most important factor for survival in both groups. In the HCV group, the status of glycaemic control was a significant independent factor of survival (P = 0.018). In the HBV group, age and the development of spontaneous bacterial peritonitis were significant. CONCLUSION: DM is more frequent in patients with HCV-related cirrhosis than in patients with HBV. Strict control of blood glucose levels could improve survival in HCV patients. A precise assessment of the risks and benefits of glycaemic control is required to reduce the mortality and morbidity of patients with cirrhosis and DM.

Adult↗
PubMed2001

A hybrid artificial neural network as a software sensor for optimal control of a wastewater treatment process.

For control and automation of biological treatment processes, lack of reliable on-line sensors to measure water quality parameters is one of the most important problems to overcome. Many parameters cannot be measured directly with on-line sensors. The accuracy of existing hardware sensors is also not sufficient and maintenance problems such as electrode fouling often cause trouble. This paper deals with the development of software sensor techniques that estimate the target water quality parameter from other parameters using the correlation between water quality parameters. We focus our attention on the preprocessing of noisy data and the selection of the best model feasible to the situation. Problems of existing approaches are also discussed. We propose a hybrid neural network as a software sensor inferring wastewater quality parameter. Multivariate regression, artificial neural networks (ANN), and a hybrid technique that combines principal component analysis as a preprocessing stage are applied to data from industrial wastewater processes. The hybrid ANN technique shows an enhancement of prediction capability and reduces the overfitting problem of neural networks. The result shows that the hybrid ANN technique can be used to extract information from noisy data and to describe the nonlinearity of complex wastewater treatment processes.

Automation↗
PubMed2000

Estrogen affects vascular tone differently according to vasoactive substances in ovariectomized Sprague-Dawley rat.

The favorable effects of estrogen on cardiovascular diseases can be explained by several mechanisms such as changes in serum lipid profiles and thrombogenecity. Estrogen also affects the vascular tone, but there has been no report in which the effect of estrogen was tested comprehensively for several vasoactive substances, especially after long-term administration. Two weeks after bilateral ovariectomy in 8-week old female Sprague-Dawley rats, placebo or 17 beta-estradiol (E2) pellets (0.5 mg; released over 3 weeks) were implanted subcutaneously. Two weeks after pellet implantation, organ chamber experiments were performed using aortae. Compared with control, E2-treated vessels showed impaired endothelium-dependent relaxation to acetylcholine. E2 enhanced the contraction to norepinephrine and U46619 and had no effect on endothelin-1-induced contraction. In contrast, the contraction to angiotensin (AT)-II was inhibited by E2. Northern blot analysis for AT1 receptor expression using cultured aortic smooth muscle cells showed no difference between control and E2-treated cells, suggesting that AT1 receptor downregulation is not the likely mechanism. These results suggest that E2 affects the vascular tone variably according to vasoactive substances.

Animals↗
PubMed1998

Control of myocardial contractile function by the level of beta-adrenergic receptor kinase 1 in gene-targeted mice.

We studied the effect of alterations in the level of myocardial beta-adrenergic receptor kinase betaARK1) in two types of genetically altered mice. The first group is heterozygous for betaARK1 gene ablation, betaARK1(+/-), and the second is not only heterozygous for betaARK1 gene ablation but is also transgenic for cardiac-specific overexpression of a betaARK1 COOH-terminal inhibitor peptide, betaARK1(+/-)betaARKct. In contrast to the embryonic lethal phenotype of the homozygous betaARK1 knockout (Jaber, M., Koch, W. J., Rockman, H. A., Smith, B., Bond, R. A., Sulik, K., Ross, J., Jr., Lefkowitz, R. J., Caron, M. G., and Giros, B. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 12974-12979), betaARK1(+/-) mice develop normally. Cardiac catheterization was performed in mice and showed a stepwise increase in contractile function in the betaARK1(+/-) and betaARK1(+/-)betaARKct mice with the greatest level observed in the betaARK1(+/-)betaARKct animals. Contractile parameters were measured in adult myocytes isolated from both groups of gene-targeted animals. A significantly greater increase in percent cell shortening and rate of cell shortening following isoproterenol stimulation was observed in the betaARK1(+/-) and betaARK1(+/-)betaARKct myocytes compared with wild-type cells, indicating a progressive increase in intrinsic contractility. These data demonstrate that contractile function can be modulated by the level of betaARK1 activity. This has important implications in disease states such as heart failure (in which betaARK1 activity is increased) and suggests that betaARK1 should be considered as a therapeutic target in this situation. Even partial inhibition of betaARK1 activity enhances beta-adrenergic receptor signaling leading to improved functional catecholamine responsiveness.

Adrenergic beta-Agonists↗
PubMed1998

Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice.

Heart failure is accompanied by severely impaired beta-adrenergic receptor (betaAR) function, which includes loss of betaAR density and functional uncoupling of remaining receptors. An important mechanism for the rapid desensitization of betaAR function is agonist-stimulated receptor phosphorylation by the betaAR kinase (betaARK1), an enzyme known to be elevated in failing human heart tissue. To investigate whether alterations in betaAR function contribute to the development of myocardial failure, transgenic mice with cardiac-restricted overexpression of either a peptide inhibitor of betaARK1 or the beta2AR were mated into a genetic model of murine heart failure (MLP-/-). In vivo cardiac function was assessed by echocardiography and cardiac catheterization. Both MLP-/- and MLP-/-/beta2AR mice had enlarged left ventricular (LV) chambers with significantly reduced fractional shortening and mean velocity of circumferential fiber shortening. In contrast, MLP-/-/betaARKct mice had normal LV chamber size and function. Basal LV contractility in the MLP-/-/betaARKct mice, as measured by LV dP/dtmax, was increased significantly compared with the MLP-/- mice but less than controls. Importantly, heightened betaAR desensitization in the MLP-/- mice, measured in vivo (responsiveness to isoproterenol) and in vitro (isoproterenol-stimulated membrane adenylyl cyclase activity), was completely reversed with overexpression of the betaARK1 inhibitor. We report here the striking finding that overexpression of this inhibitor prevents the development of cardiomyopathy in this murine model of heart failure. These findings implicate abnormal betaAR-G protein coupling in the pathogenesis of the failing heart and point the way toward development of agents to inhibit betaARK1 as a novel mode of therapy.

Animals↗
PubMed1997

Calicheamin-mediated DNA damage in a reconstituted nucleosome is not affected by histone acetylation: the role of drug structure in the target recognition process.

We have examined the role of drug structure and histone acetylation in DNA damage produced by the enediyne antibiotic calicheamicin gammaII in nucleosomes reconstituted onto the 5S rRNA gene of Xenopus borealis. Consistent with previous observations, calicheamicin damage at the 3'-end of a purine tract (positions -13 and -14) was enhanced in the nucleosome compared to the naked DNA while damage at other sites was somewhat reduced in the nucleosome. However, damage produced by esperamicin C, an analog of calicheamicin missing the terminal sugar-aromatic ring in the side chain, showed no enhancement at positions -13 and -14, and its sequence selectivity in naked DNA was markedly different from that of calicheamicin. This highlights the importance of the intact tetrasaccharide side chain in the recognition of the structural deformation occurring at the 3'-ends of purine tracts. Both drugs produced identical cleavage patterns in normal and hyperacetylated nucleosomes. Given the sensitivity of calicheamicin to local DNA conformation, this observation is consistent with other studies that suggest that histone acetylation alone does not significantly affect the local conformation of core DNA in the nucleosome.

Acetylation↗
PubMed1997

Overexpression of the rat sarcoplasmic reticulum Ca2+ ATPase gene in the heart of transgenic mice accelerates calcium transients and cardiac relaxation.

The Ca2+ ATPase of the sarcoplasmic reticulum (SERCA2) plays a dominant role in lowering cytoplasmic calcium levels during cardiac relaxation and reduction of its activity has been linked to delayed diastolic relaxation in hypothyroid and failing hearts. To determine the contractile alterations resulting from increased SERCA2 expression, we generated transgenic mice overexpressing a rat SERCA2 transgene. Characterization of a heterozygous transgenic mouse line (CJ5) showed that the amount of SERCA2 mRNA and protein increased 2. 6-fold and 1.2-fold, respectively, relative to control mice. Determination of the relative synthesis rate of SERCA2 protein showed an 82% increase. The mRNA levels of some of the other genes involved in calcium handling, such as the ryanodine receptor and calsequestrin, remained unchanged, but the mRNA levels of phospholamban and Na+/Ca2+ exchanger increased 1.4-fold and 1.8-fold, respectively. The increase in phospholamban or Na+/Ca2+ exchanger mRNAs did not, however, result in changes in protein levels. Functional analysis of calcium handling and contractile parameters in isolated cardiac myocytes indicated that the intracellular calcium decline (t1/2) and myocyte relengthening (t1/2) were accelerated by 23 and 22%, respectively. In addition, the rate of myocyte shortening was also significantly faster. In isolated papillary muscle from SERCA2 transgenic mice, the time to half maximum postrest potentiation was significantly shorter than in negative littermates. Furthermore, cardiac function measured in vivo, demonstrated significantly accelerated contraction and relaxation in SERCA2 transgenic mice that were further augmented in both groups with isoproterenol administration. Similar results were obtained for the contractile performance of myocytes isolated from a separate line (CJ2) of homozygous SERCA2 transgenic mice. Our findings suggest, for the first time, that increased SERCA2 expression is feasible in vivo and results in enhanced calcium transients, myocardial contractility, and relaxation that may have further therapeutic implications.

Animals↗
PubMed1997

Mechanism of beta-adrenergic receptor desensitization in cardiac hypertrophy is increased beta-adrenergic receptor kinase.

Pressure overload cardiac hypertrophy in the mouse was achieved following 7 days of transverse aortic constriction. This was associated with marked beta-adrenergic receptor (beta-AR) desensitization in vivo, as determined by a blunted inotropic response to dobutamine. Extracts from hypertrophied hearts had approximately 3-fold increase in cytosolic and membrane G protein-coupled receptor kinase (GRK) activity. Incubation with specific monoclonal antibodies to inhibit different GRK subtypes showed that the increase in activity could be attributed predominately to the beta-adrenergic receptor kinase (betaARK). Although overexpression of a betaARK inhibitor in hearts of transgenic mice did not alter the development of cardiac hypertrophy, the beta-AR desensitization associated with pressure overload hypertrophy was prevented. To determine whether the induction of betaARK occurred because of a generalized response to cellular hypertrophy, betaARK activity was measured in transgenic mice homozygous for oncogenic ras overexpression in the heart. Despite marked cardiac hypertrophy, no difference in betaARK activity was found in these mice overexpressing oncogenic ras compared with controls. Taken together, these data suggest that betaARK is a central molecule involved in alterations of beta-AR signaling in pressure overload hypertrophy. The mechanism for the increase in betaARK activity appears not to be related to the induction of cellular hypertrophy but to possibly be related to neurohumoral activation.

Animals↗
PubMed1996

Incorrect base insertion and prematurely terminated transcripts during T7 RNA polymerase transcription elongation past benzo[a]pyrenediol epoxide-modified DNA.

DNA replication and transcription are affected adversely by the presence of bulky adducts that are generated by the covalent binding of a variety of metabolically activated environmental pollutants to cellular DNA. When these lesions are not cleared by cellular repair enzymes prior to replication, mutations and ultimately tumor initiation can occur. Transcription and DNA repair appear to be intimately connected, since certain adducts are more efficiently removed from the transcribed strands of active loci than from non-transcribed strands and other quiescent domains in the genome. The mechanism by which RNA polymerases deal with bulky adducts during DNA transcription is therefore of great interest. The availability of site-specifically modified and stereochemically defined oligodeoxyribonucleotides derived from the covalent reaction of 7r, 8t-dihydroxy-9, 10t-epoxy- 7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) with guanine residues prompted us to study the efficiencies of transcription past these lesions using bacteriophage T7 RNA polymerase. We show here that T7 RNA polymerase can bypass such lesions in a DNA template, providing that a cytosine residue is incorporated opposite anti-BPDE-modified guanine. However, when an incorrect base (most frequently a purine) is inserted opposite the modified site, the RNA polymerase stalls, and the complex dissociates, resulting in a truncated transcript. The ability of the T7 RNA polymerase to discriminate between a correct and an incorrect inserted base and, accordingly, to continue or terminate transcription, might constitute an important mechanism that ensures the fidelity of transcription past a modified base present on the transcribed strand of the DNA template.

Bacteriophage T7↗
PubMed1996

Receptor-specific in vivo desensitization by the G protein-coupled receptor kinase-5 in transgenic mice.

Transgenic mice were generated with cardiac-specific overexpression of the G protein-coupled receptor kinase-5 (GRK5), a serine/threonine kinase most abundantly expressed in the heart compared with other tissues. Animals overexpressing GRK5 showed marked beta-adrenergic receptor desensitization in both the anesthetized and conscious state compared with nontransgenic control mice, while the contractile response to angiotensin II receptor stimulation was unchanged. In contrast, the angiotensin II-induced rise in contractility was significantly attenuated in transgenic mice overexpressing the beta-adrenergic receptor kinase-1, another member of the GRK family. These data suggest that myocardial overexpression of GRK5 results in selective uncoupling of G protein-coupled receptors and demonstrate that receptor specificity of the GRKs may be important in determining the physiological phenotype.

Animals↗
PubMed1994

Site-specific benzo[a]pyrene diol epoxide-DNA adducts inhibit transcription elongation by bacteriophage T7 RNA polymerase.

Benzo[a]pyrene, an extremely potent procarcinogen and mutagen, is metabolized to a variety of products, including the ultimate carcinogen 7,8-dihydroxy-9,10-epoxy- 7,8,9,10-tetrahydrobenzo[a]pyrene. This product of biotransformation reacts with DNA, forming a series of adducts principally at the N2 position of guanine that differ in their stereochemistry and exhibit unique biological properties. In order to gain a better understanding of the effects on RNA synthesis of these adducts, we used purified bacteriophage T7 RNA polymerase to transcribe a series of templates containing one of four stereoisomerically pure BPDE-guanine lesions--(+)-trans-,(-)-trans-,(+)-cis-anti-N2-BPDE-guanine--or no damaged bases. To construct suitable double-stranded oligodeoxynucleotides for these studies, we annealed an 11-mer containing a site-specific stereoisomerically pure N2-BPDE-guanine adduct, a 37-mer, and a 10-mer to a complementary 58-base sequence of single-stranded DNA. The oligomers were ligated, purified, and reannealed. The resulting DNA template contained the promoter for T7 RNA polymerase and a BPDE adduct at position +16 following the transcription initiation site. The results of the transcription assays clearly demonstrate that each of the adducts inhibits elongation by T7 RNA polymerase, but they do so to significantly different extents, depending on the stereochemical characteristics of the BPDE-modified guanine. The order of inhibition is (+)-trans > (-)-trans > (+)-cis > (-)-cis, when the amount of full-length transcript for each is compared to that obtained for an unmodified template. Furthermore, premature termination of RNA synthesis occurs at or near the site of the BPDE lesion as evidenced by the formation of discrete, truncated transcripts. These results might be related to the fact that the pyrenyl moiety of the trans-BPDE adducts is situated in the minor groove of double-stranded DNA, but is quasi-intercalated into the double helix in the case of the cis stereoisomers.(ABSTRACT TRUNCATED AT 250 WORDS)

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1994

Effect of corticosteroid treatment on salicylate ototoxicity.

Our previous studies showed that salicylate ototoxicity is associated with decreased levels of prostaglandins (PGs) and elevated levels of leukotrienes (LTs) in the perilymph. The purpose of this study was to determine whether or not pretreatment with corticosteroid, which suppresses both PGs and LTs in arachidonic acid metabolism, prevents salicylate ototoxicity. Salicylate ototoxicity was induced in chinchillas with or without treatment with dexamethasone. Hearing thresholds were measured by auditory brain stem response, and perilymph samples were assayed by high-performance liquid chromatography. Dexamethasone pretreatment, given by either systemic or local round window membrane application, partially prevented salicylate-induced hearing loss. Prevention of salicylate ototoxicity by dexamethasone seems to be correlated with increased PG levels and decreased LT levels in the perilymph. This is another piece of evidence that salicylate ototoxicity may be mediated by abnormal arachidonic acid metabolism in the inner ear.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

The characterization of Gardnerella vaginalis DNA using non-radioactive DNA probes.

DNA restriction profiles of various Gardnerella vaginalis isolates, generated by BamHI, EcoRI, PstI and other restriction enzymes, varied considerably. Only a few DNA fragments were identified as common in ethidium bromide fluorescence profile and Southern-blot hybridization patterns (employing a digoxigenin-labelled G. vaginalis DNA probe and an enzyme-linked immunoassay detection method). While the efficiencies of Southern-blot hybridization appeared inconsistent, in dot-blot assays, DNA from each isolate hybridized readily, enabling the detection of at least 10 ng DNA. A 5.7-kb DNA fragment from G. vaginalis ATCC 14018 genomic library, cloned in the BamHI site of pBR322, could replace the total genomic DNA probe. This specific DNA fragment was present in different sizes in 12 analysed G. vaginalis strains, describing a restriction fragment length polymorphism. In control studies, none of the DNA from bacteria other than G. vaginalis (including some genitourinary tract residents) hybridized with the G. vaginalis total or specific DNA probes. Non-radioactive G. vaginalis DNA probes can thus form the basis of a useful detection method for further studies of this organism.

Blotting, Southern↗
PubMed1991

Cisplatin based combination chemotherapy in the treatment of stage III ovarian epithelial tumors of low malignant potential.

Eleven patients diagnosed with Stage III epithelial ovarian tumors of low malignant potential were treated with a combination of cisplatin and cyslophosphamide with or without doxorubicin following primary cytoreductive surgery. Residual disease after initial cytoreduction was macroscopic in nine patients and not observable in two. Eight of the nine patients with macroscopic residual were assessed by second look laparotomy (one refused the procedure), seven showed tumor and one was found to be a complete responder. Of the two patients with no residual disease, one refused second look operation and one had a negative second look. Our findings plus those of other authors suggest that cisplatin based combination chemotherapy is of limited value in the treatment of metastatic ovarian epithelial tumors of low malignant potential.

Adult↗
PubMed1990

Adenosquamous carcinoma of the cervix: prognosis in stage IB.

The outcome of women with adenosquamous carcinoma of the cervix has been a controversial issue. To assess the prognostic significance of this cell type, the medical records of 29 patients with stage IB primary adenosquamous carcinoma of the cervix were reviewed. Twenty-six had cervical tumors measuring 3 cm or less. With a median follow-up of 60 months, the overall disease-free 5-year survival was 85%. Pelvic lymph node metastases were found in three of 19 patients (16%) with stage IB, and periaortic lymph nodes were negative in eight. A log-likelihood chi 2 test comparing lymphatic spread, recurrence rate, and 5-year disease-free survival in patients with stage IB disease and tumors less than 3 cm versus a similar group of 58 patients with pure squamous cell carcinoma of equivalent stage and comparable size treated during the same time disclosed no significant differences in any of the indicators analyzed. We conclude that stage IB adenosquamous carcinoma of the cervix does not differ in its metastatic potential or outcome from the more common pure squamous cell carcinoma.

Adenocarcinoma↗