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Biomedical subjects

S J Cho

Publications and source records attributed to S J Cho.

At least 55 records · Page 3Linked to original sources
PubMed1998

Prostaglandin F2alpha-induced luteolysis of aging corpora lutea in hysterectomized pigs.

Prostaglandins primarily of uterine origin play an important role in parturition. Hysterectomy of nongravid pigs early in the luteal phase maintains luteal function until about Day 150, whereas the duration of normal pregnancy is about 114 days. A precisely timed peak release of relaxin and coincident decrease in progesterone secretion in unmated hysterectomized gilts are similar to hormonal changes that occur a few hours before parturition. It is hypothesized that prostaglandin F2alpha (PGF2alpha) in hysterectomized pigs mimics abrupt changes in ovarian and pituitary hormone secretion seen before normal parturition and in early lactation. Unmated Yorkshire gilts were hysterectomized on Days 6-8 of a normal estrous cycle, and at 1200 h on Day 113, they were given an i.m. injection of 30 mg PGF2alpha-trihydroxymethylaminomethane (THAM) salt or PBS. None of these gilts expressed behavioral estrus immediately after PGF2alpha or vehicle treatment. On Day 113, PGF2alpha increased peak relaxin (60 ng/ml) compared with that of controls (34 ng/ml; p < 0.01), whereas progesterone decreased abruptly (4 vs. 16 ng/ml in PGF2alpha and PBS; p < 0.01). Prolactin remained at < 5 ng/ml from Day 98 to 120 in controls but peaked at 33 ng/ml immediately after PGF2alpha treatment on Day 113, and then decreased to levels similar to those of controls on Day 120. Sequential bleeding revealed an acute growth hormone release (4.5 ng/ml) immediately after PGF2alpha injection and return to basal levels (< 0.6 ng/ml) on Days 114-120. PGF2alpha induced abrupt shifts in progesterone, relaxin, prolactin, and growth hormone secretion in hysterectomized gilts that mimicked hormone changes seen in late pregnancy, parturition, and early lactation. These findings provide new insight into the role of PGF2alpha in abruptly changing hormone secretions by aging corpora lutea and the pituitary gland even in the absence of conceptuses or the uterus in the pig.

Animals↗
PubMed1998

Two uterine arterial management methods in laparoscopic hysterectomy.

OBJECTIVE: The purpose of this study was to evaluate whether laparoscopic separation with coagulation of the uterine arteries and uterosacral ligaments can be used in an attempt to improve the operative procedure when hysterectomy is carried out by laparoscopic and vaginal method. METHOD: A prospective study was carried out in 70 women who underwent laparoscopic hysterectomy excluding total laparoscopic hysterectomy. Laparoscopic uterine arterial separation with coagulation (include laparoscopic reperitonization) was performed after laparoscopic detachment of the bladder and resection of the broad ligament (or adnexa) in 39 cases (Group 1). Uterine artery was coagulated by bipolar electrocoagulator and separated from the uterine side wall by scissors. Endoloop tie was applied to the arterial pedicle, if bleeding occurred. Uterine arterial management was performed through the vaginal route (include vaginal reperitonization) after laparoscopic procedure which was finished at the lower part of broad ligament with bladder detachment in 31 cases (Group 2). RESULTS: The average duration of operation was 84.0 min and 101.8 min in Groups 1 and 2, respectively (p < 0.05). The average amount of bleeding was 154.8 ml and 298.4 ml in Groups 1 and 2, respectively (p < 0.05). Hemoglobin decreased in average by 0.9 g/100 ml and 1.6 g/100 ml in Groups 1 and 2, respectively (p < 0.05). CONCLUSION: These results demonstrate that laparoscopic management of uterine arterial pedicles after bladder detachment could reduce the duration of operation time and amount of bleeding in laparoscopic hysterectomy.

Adult↗
PubMed1998

Focus-2D: a new approach to the design of targeted combinatorial chemical libraries.

A strategy for rational design of targeted combinatorial libraries is described. The aim of this approach is to select a subset of available building blocks for the library synthesis that are most likely to be present in the active compounds. Building blocks that are used in the underlying combinatorial chemical reaction are randomly assembled to produce virtual combinatorial library compounds, which are represented by various chemical descriptors. Stochastic algorithms (simulated annealing, genetic algorithms, neural net methods) are used to search the potentially large structural space of virtual chemical libraries in order to identify compounds similar to lead compound(-s). The selection of a virtual molecule as a candidate for the targeted library is based either on its chemical similarity to a biologically active probe or on its biological activity predicted from a pre-constructed QSAR equation. Frequency analysis of building block composition of the selected virtual compounds identifies building blocks that can be used in combinatorial synthesis of chemical libraries with high similarity to the lead compound(-s). This method is applied to rational design of the library with bradykinin potentiating activity. Twenty eight bradykinin potentiating pentapeptides were used as a training set for the development of a QSAR equation, and, alternatively, two active pentapeptides, VEWAK and VKWAP, were used as probe molecules. In each case, the frequency distribution of amino acids in the top 100 peptides suggested by the method resembles the frequency distribution of amino acids found in the active peptides. The results obtained after GA optimization also compared favorably with those obtained by the exhaustive analysis of all possible 3.2 millions pentapeptides.

Algorithms↗
PubMed1997

Characterization of Erwinia carotovora subsp. carotovora LY34 endo-1,4-beta-glucanase genes and rapid identification of their gene products.

Genomic DNA of the phytopathogenic Erwinia carotovora subsp. carotovora LY34 was partially digested with Sau3AI, ligated into the BamHI site of pBlue-script II SK+, and introduced into E. coli. Two clones that were able to hydrolyse carboxymethylcellulose were selected. 1.5 kb and 1.2 kb fragments containing the celA and celB genes, respectively, were subcloned and sequenced. The celA and celB genes had open reading frames of 1,161 bp and 792 bp encoding 487 and 264 amino acid residues with calculated molecular weights of 42,003 Da and 29,890 Da, respectively. Each, CelA and CelB, carried a typical prokaryotic signal peptide of 32 and 36 amino acid residues, respectively. The apparent molecular masses of the proteins when expressed in E. coli cells were approximately 39 kDa (CelA) and 26 kDa (CelB) as assessed by CMC-SDS-PAGE. Activity staining of CMCase in an SDS-PAGE gel containing 0.1% CMC revealed that the cloned endoglucanase isozymes comigrated with the corresponding ones present in Erwinia carotovora subsp. carotovora LY34.

Amino Acid Sequence↗
PubMed1997

Blood flow velocity changes in the middle cerebral artery as an index of the chronicity of hypertension.

This study was designed to demonstrate cerebral hemodynamic changes related to hypertension using transcranial Doppler ultrasonography. We measured the flow velocities and the Gosling pulsatility index of the middle cerebral artery and the internal carotid artery in 94 stroke-free, hypertensive patients and 81 age- and gender-matched healthy controls. Compared with the control subjects, patients with a longer duration (> or = 5 years) of hypertension showed significantly lower flow velocities of the middle cerebral artery and a higher Gosling pulsatility index of the middle cerebral- and the internal carotid artery. These differences were not observed in patients with a shorter duration of hypertension (<5 years). In the patient group, the mean velocity of the middle cerebral artery was significantly and inversely correlated with the duration of hypertension. Decreased flow velocity with increased pulsatility observed in this study suggest that alterations in the small cerebral vessels and arterioles contribute primarily to cerebral hemodynamic changes occurring in long-standing hypertension and also suggest the possible usefulness of transcranial Doppler in monitoring the progression of cerebral atherogenesis related to hypertension.

Adult↗
PubMed1997

Continuous infusion of relaxin on periparturient progesterone, oxytocin and relaxin plasma concentrations and time of parturition in beef heifers.

These studies were designed to determine whether continuous i.v. infusion of increasing dosages of porcine relaxin during late pregnancy in beef heifers would influence circulating blood concentrations of relaxin, progesterone and oxytocin, and time of onset of parturition. Beef heifers were bred by artificial insemination and, on Day 277, fitted with indwelling jugular cannulas for hormone infusion and blood sampling from Day 277 to Day 286. Intravenous infusion of purified porcine relaxin (pRLX, 3000 U mg-1) was started in heifers (n = 8) at increasing dosages (200 U h-1 on Days 277 and 278, 300 U h-1 on Days 279 and 280, 500 U h-1 on Day 281, 600 U h-1 on Day 282, and 700 U h-1 on Days 283-286). Phosphate-buffered saline (PBS, 10 ml h-1) was infused during these same times to control animals (n = 6). Relaxin treatment steadily increased the circulating plasma concentration of immunoreactive relaxin to more than 120 ng ml-1 compared with less than 0.5 ng ml-1 in PBS-treated controls. Relaxin infusion in increasing dosages over the treatment time was associated with a significant decrease (P < 0.01) in plasma progesterone concentration compared with the PBS controls. The rate of change in progesterone levels between pRLX and PBS groups differed (P < 0.05) at 300 U h-1, 600 U h-1 and 700 Uh-1 dosage intervals, respectively. Plasma levels of oxytocin at 4 h intervals remained similar (P > 0.05) during the pretreatment period and throughout continuous infusion of pRLX and PBS. Mean concentrations of oxytocin in PBS control heifers peaked at 0.95 pgml-1 during the corresponding infusion of 700 Uh-1 pRLX, which peaked at 0.77 pgml-1. Although continuous i.v. infusion of relaxin resulted in a decrease in circulating blood levels of progesterone, it did not significantly reduce the interval between the beginning of pRLX treatment and parturition compared with the PBS-infused control heifers. These results indicate that continuous i.v. infusion of high levels of porcine relaxin resulted in a decrease in progesterone secretion in late pregnant beef heifers.

Animals↗
PubMed1997

A new approach to protein fold recognition based on Delaunay tessellation of protein structure.

We propose new algorithms for sequence-structure compatibility (fold recognition) searches in multi-dimensional sequence-structure space. Individual amino acid residues in protein structures are represented by their C alpha atoms; thus each protein is described as a collection of points in three-dimensional space. Delaunay tessellation of a protein generates an aggregate of space-filling, irregular tetrahedra, or Delaunay simplices. Statistical analysis of quadruplet residue compositions of all Delaunay simplices in a representative dataset of protein structures leads to a novel four body contact residue potential expressed as log likelihood factor q. The q factors are calculated for native 20 letter amino acid alphabet and several reduced alphabets. Two sequence-structure compatibility functions are computed as (i) the sum of q factors for all Delaunay simplices in a given protein, or (ii) 3D-1D Delaunay tessellation profiles where the individual residue profile value is calculated as the sum of q factors for all simplices that share this vertex residue. Both threading functions have been implemented in structure-recognizes-sequence and sequence-recognizes-structure protocols for protein fold recognition. We find that both profile and total score based threading functions can distinguish both the native fold from incorrect folds for a sequence, and the native sequence from non-native sequences for a fold.

Amino Acid Sequence↗
PubMed1996

Structure-based alignment and comparative molecular field analysis of acetylcholinesterase inhibitors.

The method of comparative molecular field analysis (CoMFA) was used to develop quantitative structure-activity relationships for physostigmine, 9-amino-1,2,3,4-tetrahydroacridine (THA), edrophonium (EDR), and other structurally diverse inhibitors of acetylcholinesterase (AChE). The availability of the crystal structures of enzyme/inhibitor complexes (EDR/AChE, THA/AChE, and decamethonium (DCM)/AChE) (Harel, M.; et al. Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 9031-9035) provided information regarding not only the active conformation of the inhibitors but also the relative mutual orientation of the inhibitors in the active site of the enzyme. Crystallographic conformations of EDR and THA were used as templates onto which additional inhibitors were superimposed. The application of cross-validated R2 guided region selection method, recently developed in this laboratory (Cho, S.J.; Tropsha, A. Cross-Validated R2 Guided Region Selection for Comparative Molecular Field Analysis (CoMFA): A Simple Method to Achieve Consistent Results. J. Med. Chem. 1995, 38, 1060-1066), to 60 AChE inhibitors led to a highly predictive CoMFA model with the q2 of 0.734.

Acetylcholinesterase↗
PubMed1996

Microbial cyanide sensor for monitoring river water.

A microbial cyanide sensor using Saccharomyces cerevisiae for monitoring a river water is described. This sensor is based on the inhibition of S. cerevisiae's respiration by cyanide. This sensor is a reactor type flow system and composed of two oxygen electrodes and a reactor which contains S. cerevisiae immobilized beads. The S. cerevisiae's respiration activity is measured using the oxygen electrodes. The sensor showed a linear response in the range from 0 to 15 microM and maintained stable response for 9 days at ambient temperature. The sensor was optimized for the monitoring of river water and was applied to river water analysis.

Biosensing Techniques↗
PubMed1996

Antitumor agents. 163. Three-dimensional quantitative structure-activity relationship study of 4'-O-demethylepipodophyllotoxin analogs using the modified CoMFA/q2-GRS approach.

Analogs of 4'O-demethylepipodophyllotoxin are considered as potential anticancer agents. We have applied comparative molecular field analysis (CoMFA) and a novel CoMFA/q2-GRS technique recently developed in our group to identify the essential structural requirements for increasing the ability of these compounds to form cellular protein-DNA complex. In addition, a new method to incorporate different types of probe atoms as part of q2-GRS routine has been developed. The best final model with 101 compounds using a combination of four different sets of probe atoms and charges [C (sp3, +1), C (sp3, 0), H (+1), and O (sp3, -1)] yielded a q 2 of 0.584 and the standard error of prediction of 0.660 at 5 principal components. The steric and electrostatic contour plots of the final model were compared with the DNA phosphate backbone environment of the DNA-4'O-demethylepipodophylltoxin analog complex, which was generated using the X-ray structure of the DNA-nogalamycin complex. The comparison reveals that the CoMFA steric and electrostatic fields are compatible with stereochemical properties of the DNA backbone. The results obtained from this study shall guide our future synthetic efforts.

Antineoplastic Agents↗
PubMed1996

Antitumor agents. 164. Podophenazine, 2'',3''-dichloropodophenazine, benzopodophenazine, and their 4 beta-p-nitroaniline derivatives as novel DNA topoisomerase II inhibitors.

We report here the synthesis and biological evaluation of novel DNA topoisomerase II inhibitors, podophenazine (8), 2'',3'' "-dichloropodophenazine (9), and benzopodophenazine (10), and their 4beta-p-nitroaniline derivatives 13-15. Among these, 4'-0-demethyl-4beta-(4'''- nitroanilino)-4-desoxypodophenazine (13) and 4'-O-demethyl-2'',3''-dichloro-4beta-(4-'''-nitroanilino)-4- desoxypodophenazine (14) were found to inhibit KB cells at sub-micromolar concentrations (IC50 = 0.11 +/- 0.03 and 0.48 +/- 0.17 microM, respectively. Against KB/7d cells (a pleiotrophic multiple drug-resistant subclone selected with etoposide which has reduced level of topoisomerase II), only compound 13 out of a target series maintained activity in the sub-micromolar concentration range with a IC 50 value of 0.56 +/- 0.13 mu M. The differential toxicity ratio for 13 [IC 50 (KB/7d)/IC 50 (KB)] was approximately 5. Unlike etoposide and its congeners, compounds 13 and 14 were found to be weak inhibitors of the catalytic activity of topoisomerase II (IC100 = > 100 and > 150 microM, respectively). In vitro protein-linked DNA complex formation assay revealed that 13 and 14, respectively, induced marginal response (13 at 1 microM, 320.3 +/- 124.5 cpm; 13 at 50 microM, 308.8 +/- 139.9 cpm; 13 at 100 mu M, 446.0 +/- 153.5 cpm) and no response (14 at 1 microM, 104.9 +/- 52.6 cpm; 14 at 50 microM, 103.3 +/- 42.6 cpm; 14 at 100 microM, 101.4 +/- 35.2 cpm) compared to the enzyme control. On the basis of these results, we conclude that the mechanism of enzyme inhibition of these compounds is distinct from that of etoposide and its congeners. We are currently investigating the mechanism(s) of action of compounds 13 and 14 as well as synthesizing other derivatives in order to better characterize structure-activity relationships of this series of compounds.

Antineoplastic Agents↗
PubMed1995

Cross-validated R2-guided region selection for comparative molecular field analysis: a simple method to achieve consistent results.

Comparative Molecular Field Analysis (CoMFA) is one of the most powerful modern tools for quantitative structure-activity relationship studies. The CoMFA predictability is conventionally characterized by a cross-validated correlation coefficient R2 (q2). Our CoMFA investigation of 4 datasets, including 7 cephalotaxine esters, 20 5-HT1A receptor ligands, 59 inhibitors of HIV protease, and 21 steroids reveals that the q2 value is sensitive to the overall orientation of superimposed molecules on a computer terminal and can vary by as much as 0.5q2 units when the orientation is varied by systematic rotation. To optimize CoMFA, we have developed a new routine, cross-validated R2-guided region selection (q2-GRS). We first subdivide the rectangular lattice obtained initially with conventional CoMFA into 125 small boxes and perform 125 independent analyses using probe atoms placed within each box with the step size of 1.0 A. We then select only those small boxes for which a q2 is higher than a specified optimal cutoff value. Finally, we repeat CoMFA with the union of small boxes selected at the previous step. Four datasets described above were used to validate this new q2-GRS routine. In each case we have obtained an orientation-independent, high q2, exceeding the one obtained with the conventional CoMFA. This method shall be used routinely in the future CoMFA studies to guarantee the reproducibility of the reported q2 values.

Algorithms↗
PubMed1995

Conformational energies of substrates and inhibitors for carboxypeptidase A: stereoelectronic effect.

Because of the complexity involved in binding of a ligand to an enzyme the conformational preference of the bound ligand has not been well understood yet. We have examined the conformational energies of ligands for carboxypeptidase A using ab initio calculations. Considering the large stereoelectronic effect of 4-5 kcal/mol, the energetic preference of the unbound ligand conformers which arises from the stereoelectronic effect appears to play a significant role in determining the bound ligand conformations.

3-Mercaptopropionic Acid↗
PubMed1992

Inhibitory effect of sulfhydryl group on Ca(2+)-ATPase activity in the plasma membrane-rich fraction from bovine parotid gland.

1. The present study demonstrated that the Ca(2+)-ATPase activity of the plasma membrane-rich fraction from bovine parotid gland was decreased by the addition of reducing agents. 2. Ca(2+)-ATPase activity staining on SDS-PAGE gels was lost in the presence of 2-mercaptoethanol. 3. Among all the reducing agents tested, GSH was the most effective in inhibiting Ca(2+)-ATPase. 4. The Ca(2+)-ATPase activity decreased by the GSH was restored by the addition of an oxidizing reagent. However, oxidation with an oxidizing reagent subsequent to alkylation of the reduced enzyme with iodoacetamide resulted in no restoration of activity. 5. The decrease of Ca(2+)-ATPase activity by GSH is due to a decrease in the Vmax of the enzyme. 6. These results suggest that the disulfide bond in this enzyme protein is necessary to maintain the activity of this enzyme.

Animals↗
PubMedDate not supplied

The length of the polyoxyethylene chain in the Triton X detergents modulates the apparent activation of neurosteroid sulfatase in bovine brain.

The effect of the Triton X series on the solubilization and enzyme activity of neurosteroid sulfatase (NSS) in the bovine midbrain was investigated. Triton X-100 and X165 stimulated NSS activity in the bovine midbrain, while Triton X-305 did not. This apparent activation was attributed to the action of the detergents, and not to the latency of the enzyme or the removal of some inhibitory substance from the microsomes. The maximum stimulation was obtained when the length of the polyoxyethylene chain of the detergent was 16.

Animals↗