Biomedical subjects

S Joo

Publications and source records attributed to S Joo.

8 recordsLinked to original sources

PubMed2004

Should erectile dysfunction be considered as a marker for acute myocardial infarction? Results from a retrospective cohort study.

The association between erectile dysfunction (ED) and acute myocardial infarction (AMI) among men was examined in the Integrated Healthcare Information Services National Managed Care Benchmark Database (IHCIS). The IHCIS is a fully de-identified, HIPAA-compliant database and includes complete medical history for more than 17 million managed care lives; data from more than 30 US health plans, covering seven census regions; and patient demographics, including morbidity, age and gender. A total of 12,825 ED patients and an equal number of male patients without ED were included in the retrospective cohort study. Logistic regression analyses were performed to assess the adjusted risk of AMI that accounted for age at ED diagnosis, smoking, obesity and medications including ACE inhibitors, beta blockers and statins. The cohort of men with ED were observed to have a two-fold increase in the risk for AMI (OR=1.99, 95% CI=1.17, 3.38) after adjusting for age at ED diagnosis, smoking, obesity, and use of ACE inhibitors, beta blockers and statins. Some evidence of a possible trend toward increased risk was detected by age group. After controlling for the aforementioned covariates and compared to men 30-39 y of age, it was noted that patients 40-44 y of age were 3.8 times more likely to develop an AMI (OR=3.76, 95% CI=1.21, 11.7), 45- to 49-y-old men were also more than three times as likely to have an AMI (OR=3.14, 95% CI=1.03, 9.64), and 50- to 55-y-old patients had a four-fold increased risk of developing AMI (OR=4.04, 95% CI=1.39, 11.7). The risk becomes more pronounced with increasing age, indicating the need for cardiologists and internists to monitor ED patients who may not necessarily present with cardiovascular symptoms.

Acute Disease↗

PubMed2003

Is erectile dysfunction predictive of peripheral vascular disease?

The association between erectile dysfunction (ED) and peripheral vascular disease (PVD) among men was examined in the Integrated Healthcare Information Services National Managed Care Benchmark Database (IHCIS). The IHCIS is a fully de-identified, Health Insurance Portability and Accountability Act compliant database and includes complete medical histories for more than 17 million managed-care lives; data from more than 30 US health plans, covering seven census regions; and patient demographics, including morbidity, age and gender. A total of 12 825 ED patients and an equal number of male patients without ED were included in the retrospective cohort study. Logistic regression analyses were performed to assess the adjusted risk of PVD that accounted for age at ED diagnosis, smoking, obesity and medications including angiotensin converting enzyme (ACE) inhibitors, beta blockers and statins. The cohort of men with ED were observed to have a 75% increase in risk for PVD (odds ratio (OR) = 1.75, 95% confidence interval (CI) = 1.06, 2.90) after adjusting for age at ED diagnosis, smoking, obesity and use of ACE inhibitors, beta blockers and statins. Some evidence of a possible trend towards increased risk was detected by age group. After controlling for the aforementioned covariates and compared to men aged 30-39 years, it was noted that patients aged 40-44 years were 2.1 times more likely to develop PVD (OR = 2.07, 95% CI = 0.89, 4.81), 45-49-year-old men were also more than twice as likely to have PVD (OR = 2.32, 95% CI = 1.03, 5.22), and 50-55-year-old patients had a three-fold increased risk of developing PVD (OR = 3.00, 95% CI = 1.40, 6.43). The results of this study indicate that ED may serve as a marker for PVD. The risk becomes more pronounced with increasing age, indicating the need for cardiologists and internists to monitor ED patients who may not necessarily present with cardiovascular symptoms.

Adult↗

PubMed1999

Roles of active site aromatic residues in catalysis by ketosteroid isomerase from Pseudomonas putida biotype B.

The aromatic residues Phe-54, Phe-82, and Trp-116 in the hydrophobic substrate-binding pocket of Delta(5)-3-ketosteroid isomerase from Pseudomonas putida biotype B have been characterized in their roles in steroid binding and catalysis. Kinetic and equilibrium binding analyses were carried out for the mutant enzymes with the substitutions Phe-54 --> Ala or Leu, Phe-82 --> Ala or Leu, and Trp-116 --> Ala, Phe, or Tyr. The removal of their bulky, aromatic side chains at any of these three positions results in reduced k(cat), particularly when Phe-82 or Trp-116 is replaced by Ala. The results are consistent with the binding interactions of the aromatic residues with the bound steroid contributing to catalysis. All the mutations except the F82A mutation increase K(m); the F82A mutation decreases K(m) by ca. 3-fold, suggesting a possibility that the phenyl ring at position 82 might be unfavorable for substrate binding. The K(D) values for d-equilenin, an intermediate analogue, suggest that a space-filling hydrophobic side chain at position 54, a phenyl ring at position 82, and a nonpolar aromatic or small side chain at position 116 might be favorable for binding the reaction intermediate. In contrast to the increased K(D) for equilenin, the enzymes with any substitutions at positions 54 and 116 display a decreased K(D) for 19-nortestosterone, a product analogue, indicating that Phe-54 and Trp-116 might be unfavorable for product binding. The crystal structure of F82A determined to 2.1-A resolution reveals that Phe-82 is important for maintaining the active site geometry. Taken together, our results demonstrate that Phe-54, Phe-82, and Trp-116 contribute differentially to the stabilization of steroid species including substrate, intermediate, and product.

Alanine↗

PubMed1999

Auxin and brassinosteroid differentially regulate the expression of three members of the 1-aminocyclopropane-1-carboxylate synthase gene family in mung bean (Vigna radiata L.).

Indole-3-acetic acid (IAA) markedly increased ethylene production by inducing the expression of three 1aminocyclopropane-1-carboxylate (ACC) synthase cDNAs (pVR-ACS1, pVR-ACS6 and pVR-ACS7) in mung bean hypocotyls. Results from nuclear run-on transcription assay and RNA gel blot studies revealed that all three genes were transcriptionally active displaying unique patterns of induction by IAA and various hormones in etiolated hypocotyls. Particularly, 24-epibrassinolide (BR), an active brassinosteroid, specifically enhanced the expression of VR-ACS7 by a distinct temporal induction mechanism compared to that of IAA. In addition, BR synergistically increased the IAA-induced VR-ACS6 and VR-ACS7 transcript levels, while it effectively abolished both the IAA- and kinetin-induced accumulation of VR-ACS1 mRNA. In light-grown plants, VR-ACS1 was induced by IAA in roots, and VR-ACS6 in epicotyls. IAA- and BR-treatments were not able to increase the VR-ACS7 transcript in the light-grown tissues. These results indicate that the expression of ACC synthase multigene family is regulated by complex hormonal and developmental networks in a gene- and tissue-specific manner in mung bean plants. The VR-ACS7 gene was isolated, and chimeric fusion between the 2.4 kb 5'-upstream region and the beta-glucuronidase (GUS) reporter gene was constructed and introduced into Nicotiana tabacum. Analysis of transgenic tobacco plants revealed the VR-ACS7 promoter-driven GUS activity at a highly localized region of the hypocotyl-root junction of control seedlings, while a marked induction of GUS activity was detected only in the hypocotyl region of the IAA-treated transgenic seedlings where rapid cell elongation occurs. Although there was a modest synergistic effect of BR on the IAA-induced GUS activity, BR alone failed to increase the GUS activity, suggesting that induction of VR-ACS7 occurs via separate signaling pathways in response to IAA and BR. A scheme of the multiple regulatory pathways for the expression of ACC synthase multigene family by auxin and BR is presented.

Brassinosteroids↗

PubMed1999

A novel member of murine Polycomb-group proteins, Sex comb on midleg homolog protein, is highly conserved, and interacts with RAE28/mph1 in vitro.

The Polycomb group of (PcG) genes were originally described in Drosophila, but many PcG genes have mammalian homologs. Genetic studies in flies and mice show that mutations in PcG genes cause posterior transformations caused by failure to maintain repression of homeotic loci, suggesting that PcG proteins have conserved functions. The Drosophila gene Sex comb on midleg (Scm) encodes an unusual PcG protein that shares motifs with the PcG protein polyhomeotic, and with a Drosophila tumor suppressor, lethal(3)malignant brain tumor (l(3)mbt). Expressed sequence tag (EST) databases were searched to recover putative mammalian Scm homologs, which were used to screen murine cDNA libraries. The recovered cDNA encodes two mbt repeats and the SPM domain that characterize Scm, but lacks the cysteine clusters and the serine/threonine-rich region found at the amino terminus of Scm. Accordingly, we have named the gene Sex comb on midleg homolog 1 (Scmh1). Like their Drosophila counterparts, Scmh1 and the mammalian polyhomeotic homolog RAE28/mph1 interact in vitro via their SPM domains. We analyzed the expression of Scmh1 and rae28/mph1 using northern analysis of embryos and adult tissues, and in situ hybridization to embryos. The expression of Scmh1 and rae28/mph1 is well correlated in most tissues of embryos. However, in adults, Scmh1 expression was detected in most tissues, whereas mph1/rae28 expression was restricted to the gonads. Scmh1 is strongly induced by retinoic acid in F9 and P19 embryonal carcinoma cells. Scmh1 maps to 4D1-D2.1 in mice. These data suggest that Scmh1 will have an important role in regulation of homeotic genes in embryogenesis and that the interaction with RAE28/mph1 is important in vivo.

Amino Acid Sequence↗

PubMed1997

High-resolution crystal structures of delta5-3-ketosteroid isomerase with and without a reaction intermediate analogue.

Bacterial Delta5-3-ketosteroid isomerase (KSI) catalyzes a stereospecific isomerization of steroid substrates at an extremely fast rate, overcoming a large disparity of pKa values between a catalytic residue and its target. The crystal structures of KSI from Pseudomonas putida and of the enzyme in complex with equilenin, an analogue of the reaction intermediate, have been determined at 1.9 and 2.5 A resolution, respectively. The structures reveal that the side chains of Tyr14 and Asp99 (a newly identified catalytic residue) form hydrogen bonds directly with the oxyanion of the bound inhibitor in a completely apolar milieu of the active site. No water molecule is found at the active site, and the access of bulk solvent is blocked by a layer of apolar residues. Asp99 is surrounded by six apolar residues, and consequently, its pKa appears to be elevated as high as 9.5 to be consistent with early studies. No interaction was found between the bound inhibitor and the residue 101 (phenylalanine in Pseudomonas testosteroni and methionine in P. putida KSI) which was suggested to contribute significantly to the rate enhancement based on mutational analysis. This observation excludes the residue 101 as a potential catalytic residue and requires that the rate enhancement should be explained solely by Tyr14 and Asp99. Kinetic analyses of Y14F and D99L mutant enzymes demonstrate that Tyr14 contributes much more significantly to the rate enhancement than Asp99. Previous studies and the structural analysis strongly suggest that the low-barrier hydrogen bond of Tyr14 (>7.1 kcal/mol), along with a moderate strength hydrogen bond of Asp99 ( approximately 4 kcal/mol), accounts for the required energy of 11 kcal/mol for the transition-state stabilization.

Aspartic Acid↗

PubMed1997

Mutational analysis of the three cysteines and active-site aspartic acid 103 of ketosteroid isomerase from Pseudomonas putida biotype B.

In order to clarify the roles of three cysteines in ketosteroid isomerase (KSI) from Pseudomonas putida biotype B, each of the cysteine residues has been changed to a serine residue (C69S, C81S, and C97S) by site-directed mutagenesis. All cysteine mutations caused only a slight decrease in the k(cat) value, with no significant change of Km for the substrate. Even modification of the sulfhydryl group with 5,5'-dithiobis(2-nitrobenzoic acid) has almost no effect on enzyme activity. These results demonstrate that none of the cysteines in the KSI from P. putida is critical for catalytic activity, contrary to the previous identification of a cysteine in an active-site-directed photoinactivation study of KSI. Based on the three-dimensional structures of KSIs with and without dienolate intermediate analog equilenin, as determined by X-ray crystallography at high resolution, Asp-103 was found to be located within the range of the hydrogen bond to the equilenin. To assess the role of Asp-103 in catalysis, Asp-103 has been replaced with either asparagine (D103N) or alanine (D103A) by site-directed mutagenesis. For D103A mutant KSI there was a significant decrease in the k(cat) value: the k(cat) of the mutant was 85-fold lower than that of the wild-type enzyme; however, for the D103N mutant, which retained some hydrogen bonding capability, there was a minor decrease in the k(cat) value. These findings support the idea that aspartic acid 103 in the active site is an essential catalytic residue involved in catalysis by hydrogen bonding to the dienolate intermediate.

Aspartic Acid↗

PubMed1995

The role of contrast enhanced computed tomography in the diagnosis of low density pulmonary nodules.

Contrast enhanced CT manifestations of 141 pulmonary nodules having internal density less than 40 HU were evaluated to study the prevalence of causative disease and their differential points. Tuberculosis (n = 79) was most common, active in 96%. There were 22 cancers, 10 abscesses, 9 paragonimiases, 8 cysts, 7 metastases, 4 aspergillomas without air meniscus sign, and so on. 35% of the benign lesions were greater than 3 cm in diameter and 67% of benign lesions did not show a smooth outer margin. Lung cysts and aspergillomas showed relatively thin peripheral enhanced rim (PER), sharp transitional zone (TZ), a smooth inner border (IB), and homogeneous low densities (LD). Tuberculous nodules tended to be smaller in size with thin PER and most had smooth IB and homogeneous LD. Paragonimiasis, abscess, and cancer tended to present with thick PER and lobulated IB. Lung abscess and paragonimiasis both showed homogeneous LD and narrow TZ. However, in paragonimiasis, multiple locules were seen. Lung cancer showed wider TZ and heterogeneous LD. The size and outer margin of pulmonary nodules as a diagnostic criteria is less useful in LD pulmonary nodule. Therefore, CT can be more useful in differentiating the benign from the malignant lesions by observing a more specific and characteristic pattern of peripheral enhanced rim, transitional zone, inner border, and homogeneity of low density area.

Adolescent↗