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Biomedical subjects

D W Lee

Publications and source records attributed to D W Lee.

At least 73 records · Page 4Linked to original sources
PubMed1999

Identification of a gene, SOO1, which complements osmo-sensitivity and defect in in vitro beta1,3-glucan synthase activity in Saccharomyces cerevisiae.

The soo1-1 (for suppressor of osmo-sensitivity) mutation results in a temperature-dependent osmo-sensitive phenotype at non-permissive temperature (37 degrees C), makes yeast cells more susceptible to Zymolyase and affects in vitro beta1,3-glucan synthase activity level. Transformation of soo1-1 mutant by SOO1 gene reverses these effects. Nucleotide sequencing of SOO1 revealed that this gene is identical to the recently reported alpha-COP that is involved in the intracellular protein translocation from endoplasmic reticulum to Golgi and vice versa. Although the soo1-1 mutant strain showed osmotically remediable growth at 37 degrees C, SOO1 disruptants could not grow in any culture conditions. Analysis of cell wall fractions revealed that the soo1-1 mutation causes a decrease in in vitro beta1,3-glucan synthase activity, and, thus, a subsequent alteration of the cell wall composition.

Cell Wall↗
PubMed1999

Endoscopic retreatment compared with surgery in patients with recurrent bleeding after initial endoscopic control of bleeding ulcers.

BACKGROUND AND METHODS: After endoscopic treatment to control bleeding of peptic ulcers, bleeding recurs in 15 to 20 percent of patients. In a prospective, randomized study, we compared endoscopic retreatment with surgery after initial endoscopy. Over a 40-month period, 1169 of 3473 adults who were admitted to our hospital with bleeding peptic ulcers underwent endoscopy to reestablish hemostasis. Of 100 patients with recurrent bleeding, 7 patients with cancer and 1 patient with cardiac arrest were excluded from the study; 48 patients were randomly assigned to undergo immediate endoscopic retreatment and 44 were assigned to undergo surgery. The type of operation used was left to the surgeon. Bleeding was considered to have recurred in the event of any one of the following: vomiting of fresh blood, hypotension and melena, or a requirement for more than four units of blood in the 72-hour period after endoscopic treatment. RESULTS: Of the 48 patients who were assigned to endoscopic retreatment, 35 had long-term control of bleeding. Thirteen underwent salvage surgery, 11 because retreatment failed and 2 because of perforations resulting from thermocoagulation. Five patients in the endoscopy group died within 30 days, as compared with eight patients in the surgery group (P=0.37). Seven patients in the endoscopy group (including 6 who underwent salvage surgery) had complications, as compared with 16 in the surgery group (P=0.03). The duration of hospitalization, the need for hospitalization in the intensive care unit and the resultant duration of that stay, and the number of blood transfusions were similar in the two groups. In multivariate analysis, hypotension at randomization (P=0.01) and an ulcer size of at least 2 cm (P=0.03) were independent factors predictive of the failure of endoscopic retreatment. CONCLUSIONS: In patients with peptic ulcers and recurrent bleeding after initial endoscopic control of bleeding, endoscopic retreatment reduces the need for surgery without increasing the risk of death and is associated with fewer complications than is surgery.

Aged↗
PubMed1999

Effect of pineal indoles on the chick embryo.

In a study on the embryotoxicity of pineal indoles on developing chick embryos in vivo, the pineal indoles--namely, melatonin (MEL), methoxytryptamine (MTA) and methoxytryptophol (MTP)--were injected into the yolk sacs of the chick embryos through the air chambers of the eggs on the 4th day of incubation. The eggs were opened and the embryos examined after 6, 10 or 14/15 days of incubation. Abnormalities were found to occur mainly in the 6- and 10-day-old embryos, which exhibited external malformations such as twisted vertebral column, abdominal hernia, exteriorization of heart and viscera, defects of eye, beak and limb. From the results obtained from embryos on the 14th or 15th day of incubation, MEL was found to be the most toxic indole in regard to the mortality induced, whereas MTA had the highest teratogenicity because of the frequent incidence of abnormal embryos. Effect of MTP treatment on the development of chick embryos varied greatly between doses, and there were no abnormal embryos found on the 14th or 15th day of incubation.

5-Methoxytryptamine↗
PubMed1999

Thermolabile 8-hydroxyguanine DNA glycosylase with low activity in senescence-accelerated mice due to a single-base mutation.

8-hydroxyguanine (8-oxoguanine; oh8Gua) DNA glycosylase (OGG1) repairs oh8Gua, a highly mutagenic oxidative DNA damage. In the present study, we compared two strains of senescence-accelerated mouse (SAM) expressing senescence-prone phenotypes, SAMP1 and SAMP8, with one strain of SAM expressing senescence-resistant phenotype, SAMR1. We found three distinct characteristics of OGG1 in SAMPs: (i) low activity (10-40% of the SAMRI enzyme in all organs and ages observed), (ii) thermolability, and (iii) mutation from Arg (CGG) in SAMR1 to Trp (TGG) at codon 304. There was no difference in the levels of mRNA and protein. As expected, oh8Gua level in tissues was higher in the SAMPs. In contrast, O6-methylguanine-DNA methyltransferase, which repairs alkylated DNA, showed no difference in its activity. The impairment of oh8Gua repair activity caused by the 304 mutation in OGG1 may be one of the factors contributing to the high somatic mutation rate and the accelerated senescence observed in these strains.

Aging↗
PubMed1999

A comparative molecular field analysis and molecular modelling studies on pyridylimidazole type of angiotensin II antagonists.

A large number of compounds known as "AII (Angiotensin II) antagonists" have been developed for the treatment of various heart diseases such as hypertension, congestive heart failure, and chronic renal failure. Most of the currently known AII receptor antagonists share a similar chemical structure, consisting of nitrogen atoms, a lipophilic alkyl side chain and an acidic group. As a new series, we have designed and synthesized various pyridylimidazole derivatives. In this report we would like to discuss the structure-activity relationship of these series of compounds using the comparative molecular field analysis (CoMFA) methods. We could come up with a good CoMFA model (cross-validated and conventional r2 values equal to 0.702 and 0.991, respectively) and the validity of the model was confirmed by synthesizing and measuring their biological activity of additional 6 compounds suggested by the model. This result provides additional information on the structural requirement for structurally diverse group of AII receptor antagonists.

Angiotensin II↗
PubMed1999

Solution structure of a new hypothalamic neuropeptide, human hypocretin-2/orexin-B.

Orexin-A and orexin-B (also called hypocretin-1 and hypocretin-2, respectively) are novel hypothalamic neuropeptides encoded by a single mRNA transcript; they stimulate food intake. We have determined the three-dimensional solution structure of human hypocretin-2/orexin-B using two-dimensional 1H-NMR data and dynamical simulated annealing calculations. On the basis of NOEs, 3JHNalpha coupling constants and hydrogen-deuterium exchange rates together with chemical shift indices, human hypocretin-2/orexin-B was deduced to consist of two alpha-helices connected with a short linker in both H2O and 30% trifluoroethanol solutions. The helical axis of helix I is oriented about 60-80 degrees relative to helix II. Hybrid distance geometry and simulated-annealing protocols were used to generate an ensemble of 30 structures with no constraint violations greater than 0.03 nm for distances and 3 degrees for angles. In addition, human hypocretin-2/orexin-B shares a similar secondary-structural motif with human neuropeptide Y. This result can form the basis for further study on ligand-receptor recognition of human orexin receptors.

Amino Acid Sequence↗
PubMed1999

ERCP and pyogenic liver abscess.

BACKGROUND: Liver abscess is commonly biliary in origin. We assessed the role of endoscopic retrograde cholangiopancreatography (ERCP) in patients with pyogenic liver abscesses. METHODS: Between January 1986 and December 1997, 63 patients with pyogenic liver abscesses were referred for ERCP. Twenty-one patients had a history of previous biliary procedures including cholecystectomy (21), biliary-enteric bypass (9), surgical sphincteroplasty (5), and endoscopic sphincterotomy (2). Demographic data, clinical features, biochemical parameters, treatment, clinical progress, and follow-up were recorded and analyzed. RESULTS: Two patients required laparotomy and 61 patients underwent guided aspiration and/or drainage at a median interval of 3 days after presentation. ERCP was performed at a median of 8 days (range 1 to 69 days) after initial treatment and succeeded in 90% of cases with no associated complication or death. Abnormalities were shown in 29 (46%) patients: biliary obstruction due to stones or strictures (15), ductal dilatation alone (7), spontaneous choledochoduodenal fistula (3), communication between abscesses and biliary tree (3), and splaying of biliary ducts by space-occupying effect (2). No abnormality was found in 34 patients. Eight patients underwent endoscopic therapy including sphincterotomy (5), stone extraction (6), and nasobiliary drainage (2). Overall mortality rate from liver abscesses was 6%. CONCLUSIONS: ERCP is useful in the treatment of patients with pyogenic liver abscesses.

Adolescent↗
PubMed1999

Alteration of free radical metabolism in the brain of mice infected with scrapie agent.

Alteration of free radical metabolism in the mouse brain by scrapie infection was evaluated. The infection of mice with scrapie agent, 87V strain, slightly increased the activities of catalase and glutathione-S-transferase, while it had no effect on glutathione peroxidase, glutathione reductase, and Cu, Zn-superoxide dismutase. Results show that the scrapie infection decreased the activity of mitochondrial Mn-superoxide dismutase by 50% but increased that of monoamine oxidase (p < 0.05). Scrapie infection also increased the rate of mitochondrial superoxide generation (p < 0.05). Following scrapie infection, the level of free-sulfhydryl compounds in brain homogenates slightly decreased, but the content of thiobarbituric-acid-reactive substances and malondialdehyde increased significantly. Electron microscopy indicated that the ultrastructure of mitochondria was destroyed in the brain of scrapie-infected mice. These results suggest that elevated oxygen free radical generation and lowered scavenging activity in mitochondria might cause the free radical damage to the brain. Such deleterious changes in mitochondria may contribute to the development of prion disease.

Animals↗
PubMed1999

Inhibitory effects of leptin-related synthetic peptide 116-130 on food intake and body weight gain in female C57BL/6J ob/ob mice may not be mediated by peptide activation of the long isoform of the leptin receptor.

We recently reported that intraperitoneal administration of leptin-related synthetic peptide 116-130 [LEP-(116-130)] resulted in reduced food intake and significant weight loss in homozygous female C57BL/6J ob/ob mice. In this study, we used two in vitro bioassays to show that the interaction of LEP-(116-130) with the long form of the leptin receptor (OB-Rb), the receptor isoform that is predominantly expressed in the hypothalamus, is not required for the observed in vivo effects of the peptide on energy balance. LEP-(116-130) was unable to compete the binding of alkaline phosphatase-leptin fusion protein to OB-R. Moreover, LEP-(116-130) was unable to activate signal transduction by OB-Rb in vitro. In homozygous female C57BLKS/J-m db/db mice that do not express OB-Rb, intraperitoneal administration of LEP-(116-130) reduced body weight gain and blood glucose levels but not food intake, which further supports a mechanism of action that does not require peptide interaction with OB-Rb.

Animals↗
PubMed1998

Determination of organophosphorus pesticides in wheat flour by supercritical fluid extraction and gas chromatography with nitrogen-phosphorus detection.

Application of supercritical fluid extraction (SFE) for selective isolation of organophosphorus pesticides from a real-world matrix (wheat flour) has been described. The method uses extraction with supercritical carbon dioxide at 206.8 bar and 60 degrees C, followed by quantitation by gas chromatography with nitrogen-phosphorous detection without clean-up of the extracts. Comparison of SFE with a method currently employed for sample preparation (i.e., organic solvent extraction followed by liquid-liquid extraction and gel permeation chromatography clean-up) shows that the SFE technique simplifies the sample preparation step and speeds up the determination of organophosphorus pesticides in flour. Extraction times were 60 min for a 7 g sample size. This technique was able to determine organophosphorus pesticides (ethoprophos, diazinon, chlorpyrifos methyl, fenitrothion, parathion, phenthoate, EPN) in samples at the 10 ng/g level.

Chlorpyrifos↗
PubMed1998

Bacteria in semen used for IVF affect embryo viability but can be removed by stripping cumulus cells by vortexing.

Bacterial contamination of in vitro vs in vivo produced embryos presents a particular danger because of the alteration of the zona pellucida and the use of various biological products during culture. Our objective was to investigate the effects of semen contaminated with bacteria on IVF of bovine oocytes and to determine if removal of cumulus cells by vortexing as opposed to pipetting would reduce contamination and improve subsequent embryonic development. Semen from 5 bulls of the Native Korean breed (Bulls A, B, C, D, E) was used for IVF of matured oocytes. Preliminary studies had shown that the semen from Bulls A, B, D and E but not Bull C was contaminated with various species of common bacteria. After IVF, the cumulus cells surrounding the oocytes were removed either by pipetting or vortexing. Viability and cleavage rates of the resulting zygotes was assessed after 44 h in culture. When cumulus cells were removed by pipetting, only zygotes derived from oocytes that were fertilized with uncontaminated semen from Bull C developed to morula and blastocyst stages; zygotes derived from oocytes that were fertilized with contaminated semen from Bulls A, B, D and E started to degenerate, and the culture media became noticeably turbid. When cumulus cells were removed by vortexing, zygotes derived from oocytes fertilized with either contaminated or uncontaminated semen showed good rates of development (16 to 32%) to morula or blastocyst stages. From these results it can be concluded that the bacteria introduced with the semen contaminated the in vitro system and severely reduced the viability of the embryos. In contrast, complete removal of the cumulus cells with vortexing, as opposed to pipetting, reduced the contamination of the culture medium, allowing embryonic development to take place.

Animals↗
PubMed1998

Biological, immunological, and genetic analysis of Bacillus thuringiensis isolated from granary in Korea.

To isolate a naturally occurring novel Bacillus thuringiensis strain, we investigated the distribution, toxicity, morphology, H serotype, and gene type of B. thuringiensis from residue samples of granary in Korea. A total of 163 B. thuringiensis isolates out of 411 samples producing spore and crystal were obtained. In toxicity tests, 80% of all isolates were toxic to lepidoptera, and 12% were not toxic to any of tested insects. And dipteran-active and lepidopteran/dipteran-active isolates were rare (2% and 6%, respectively). 152 B. thuringiensis isolates produced typical rhomboidal crystals, and the remainder produced parasporal inclusions with various morphologies. Serological test showed that B. thuringiensis isolates in granary represented 12 H serotypes, indicating varied distribution of B. thuringiensis. Of these, the serotype 3ab predominated, followed by the serotype 7 and 4ac. B. thuringiensis isolates of the serotype 3ab, 4ac, 5ab, 7, 8ab, 9, and 23 were toxic to lepidoptera, and the serotype 8bd, 12, 18, and 20ac were nontoxic, while 14 isolates were untypable by 33 B. thuringiensis H antisera. The frequency of toxicity against lepidoptera and diptera was primarily highly toxic. PCR analysis using cryI gene type-specific primers showed that cryIA(b) genes are frequently found and cryIE gene exists in only one isolate. Analysis of B. thuringiensis crystals and plasmid DNAs indicated a diversity of crystal and gene types.

Animals↗
PubMed1998

Distribution, serological identification, and PCR analysis of Bacillus thuringiensis isolated from soils of Korea.

A total, 58 strains of Bacillus thuringiensis were isolated from soils of various regions in Korea. Serological tests showed that B. thuringiensis isolates represented 10 H serotypes, indicating a varied flora of B. thuringiensis. But the H serotypes did not have a significantly uneven distribution, ranging from 1 to 11 isolates. In toxicity tests, 35% of all isolates were toxic to lepidoptera, 20% were toxic to diptera, and 9% were non-toxic isolates. Especially, a large number of lepidopteran/dipteran-active isolates (36%) were found. Forty all lepidopteran-active isolates produced typical rhomboidial inclusions, and the remainder, which belong to dipteran-active and non-toxic isolates, were spherical in shape. In addition, lepidopteran/dipteran-active isolates produced rhomboidal or spherical inclusions. PCR analysis using cryI, II, III, IV, and V gene-specific primers showed that the frequency of the cryIC gene (57%) predominated, followed by the cryIA(b) (45%) and cryIIA genes (34%). But, the cryIE, cryIF, cryIII, cryIVC and cryV genes were not reactive. Several isolates had unusual PCR products and multiple insecticidal crystal protein genes. PCR results showed varied distribution of the cry-type gene. Seven isolates were selected for evaluation of novel activity according to the following criteria: flagellar serotypes, parasporal inclusion morphology, SDS-PAGE, plasmid DNA patterns, toxicity, and the cry-type gene in PCR analysis. Two isolates, named S333 (H7) and S225 (H7), among them synthesized PCR products of the cryIC gene, but the S333 isolate producing rhomboidal inclusion was toxic to both Plutella xylostella and Culex pipiens, whereas the S225 isolate having toxicity to only C. pipiens produced spherical inclusion.

Animals↗
PubMed1998

A randomized comparison of acute phase response and endotoxemia in patients with perforated peptic ulcers receiving laparoscopic or open patch repair.

BACKGROUND: In patients with peritonitis from perforated peptic ulcers, we compared acute stress responses, endotoxemia, and bacteremia following laparoscopic or open surgery. PATIENTS AND METHODS: Consecutive patients with peritonitis from perforated peptic ulcers were randomized to receive laparoscopic sutured or open omental repair. Undiluted peritoneal fluid was obtained at surgery for quantitative bacterial and endotoxin (Limulus Amoebocyte Lysate) assay. Serial blood samples were taken at 0, 30, 60, 90, 120, and 180 minutes, and at 12, 24, 48, 72, and 120 hours for determinations of quantitative bacterial and endotoxin assays, interleukin-6 (IL-6), C-reactive protein (CRP), and cortisol. RESULTS: Twenty-two patients were randomized: laparoscopy group (n = 12), open repair group (n = 10). Conversions were required in 3 patients assigned to laparoscopy, leaving 9 patients for analysis. The two groups were comparable in their demographic data, median duration of perforation (13.5 hours versus 10 hours), severity of peritoneal contamination as indicated by viable bacterial count (5.9 x 102 versus 1.5 x 10(2) colony forming unit/mL) and endotoxin concentration in peritoneal fluid (27.2 versus 24.6 EU/mL). No significant endotoxemia or bacteremia was detected in these patients. Median interleukin-6 was highest at 0 hour (1520 versus 962 pg/mL) and fell rapidly following surgery. C-reactive protein peaked at 24 hours and plateaued thereafter. Cortisol was highest intraoperatively and fell thereafter. No difference was noted between the two treatment groups with respect to these inflammatory markers (IL-6 P = 0.19, CRP P = 0.14, cortisol P = 0.56, multivariate analysis of variance). CONCLUSION: Endotoxemia and bacteremia are insignificant in most patients with perforated peptic ulcers. In patients with perforated peptic ulcers, laparoscopic patch repair does not reduce acute stress responses when compared with open surgery.

Acute-Phase Proteins↗
PubMed1998

Inhibition of 7-ethoxycoumarin O-deethylase activity in rat liver microsomes by naturally occurring flavonoids: structure-activity relationships.

1. The inhibitory effects of several naturally occurring flavonoids and related compounds on cytochrome P450-dependent 7-ethoxycoumarin O-deethylase (ECOD) and the structure-activity relationships were studied in liver microsomes from rats treated with 3-methylcholanthrene (MC). 2. All the flavonoids (flavone, apigenin, chrysin, flavonol, fisetin, kaempferol, morin, myrisetin, quercetin, flavanone, hesperetin and naringenin) studied inhibited microsomal ECOD activity in the following order: flavones > flavonols > flavanones, were mixed type inhibitors and had Ki in the range of 0.17-4.5 microM. (+/-)-Catechin had no effect. 3. The double bond between C2 and C3 of the C ring, the keto group and hydroxyl group of this ring in the flavonoids seem to play major roles in inhibiting the ECOD activity. 4. The hydroxyl groups in the C5 and C7 positions of A ring in the flavone and the hydroxyl group in the C3 position of C ring in the flavonol classes, respectively, were important factors for the inhibition of the enzyme. 5. In a series of 3, 5, 7-trihydroxyflavones, the hydroxyl group at the C4 in the B ring was also an important factor for the inhibition of ECOD activity, but hydroxyl groups in other positions of the B ring had little effect on the inhibition. 6. We conclude that all the flavonoids studied inhibit ECOD activity by interfering with the binding of substrate to the active site and other site(s) of the enzyme and that their structural differences lead to different binding affinities at the active site and possibly to binding at other site(s) of the enzyme for the flavonoids.

7-Alkoxycoumarin O-Dealkylase↗