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Biomedical subjects

M H Lee

Publications and source records attributed to M H Lee.

At least 109 records · Page 6Linked to original sources
PubMed2001

A deubiquitinating enzyme, UCH/CeUBP130, has an essential role in the formation of a functional microtubule-organizing centre (MTOC) during early cleavage in C. elegans.

BACKGROUND: Deubiquitinating enzymes generate monomeric ubiquitin in protein degradation pathways and are known to be important for the early development in many organisms. RESULTS: RNA interference experiments targeted for a UBP homologue, UCH/CeUBP130, in C. elegans resulted in cell division defective embryos. Immunostaining localized UCH/CeUBP130 in the sperm and at the microtubule-organizing centre (MTOC) during early cleavage. Furthermore, the embryonic lethal phenotype was rescued by mating with wild-type males. CONCLUSIONS: Since it is known that the MTOC in the fertilized embryo is contributed by sperm asters in C. elegans, we suggest that UCH/CeUBP130 and ubiquitin protein degradation pathways may be involved in microtubule-based sperm aster formation. Therefore UCH/CeUBP130 is necessary for the formation of a functional MTOC in the fertilized embryo of C. elegans.

Amino Acid Sequence↗
PubMed2001

Effect of proteasome inhibition on cellular oxidative damage, antioxidant defences and nitric oxide production.

The ubiquitin/proteasome pathway plays an essential role in protein turnover in vivo, and contributes to removal of oxidatively damaged proteins. We examined the effects of proteasome inhibition on viability, oxidative damage and antioxidant defences in NT-2 and SK-N-MC cell lines. The selective proteasome inhibitor, lactacystin (1 microM) caused little loss of viability, but led to significant increases in levels of oxidative protein damage (measured as protein carbonyls), ubiquitinated proteins, lipid peroxidation and 3-nitrotyrosine, a biomarker of the attack of reactive nitrogen species (such as peroxynitrite, ONOO(-)) upon proteins. Higher levels (25 microM) of lactacystin did not further increase the levels of carbonyls, lipid peroxidation, 3-nitrotyrosine, or ubiquitinated proteins, but produced increases in the levels of 8-hydroxyguanine (a biomarker of oxidative DNA damage) and falls in levels of GSH. Lactacystin (25 microM) caused loss of viability, apparently by apoptosis, and also increased production of nitric oxide (NO.) (measured as levels of NO2- plus NO3-) by the cells; this was inhibited by N-nitro-L-arginine methyl ester (L-NAME), which also decreased cell death induced by 25 microM lactacystin and decreased levels of 3-nitrotyrosine. The NO. production appeared to involve nNOS; iNOS or eNOS were not detectable in either cell type. Another proteasome inhibitor, epoxomicin, had similar effects.

Acetylcysteine↗
PubMed2001

Modulation of QT interval by cardiac sympathetic nerve sprouting and the mechanisms of ventricular arrhythmia in a canine model of sudden cardiac death.

INTRODUCTION: We previously reported that there is a high incidence of sudden cardiac death (SCD) in dogs with myocardial infarction (MI), complete AV block (CAVB), and nerve growth factor (NGF) infusion to the left stellate ganglion (LSG). Whether or not QT interval prolongation underlines the mechanism of SCD was unclear. METHODS AND RESULTS: We analyzed QT intervals in three groups of dogs. All dogs had CAVB and MI. The LSG group (n = 9) and right stellate ganglion (RSG) group (n = 6) received NGF infusion via the osmotic pumps over a 5-week period to LSG and RSG, respectively. The control group (n = 6) received no NGF. The dogs either died suddenly or were sacrificed within 2 to 3 months after MI. Heart rhythm and QT and RR intervals were monitored using implantable cardioverter defibrillator ECG recordings. There was a time-dependent increase of QTc intervals in the LSG group and a time-dependent decrease of QTc intervals in the RSG group. At the end of NGF infusion, QTc intervals in the LSG group (408 +/- 41 msec) were significantly longer than those in the control (350 +/- 41 msec; P < 0.05) and RSG groups (294 +/- 23 msec; P < 0.01). In the LSG group, 4 of 9 dogs died of SCD. There was no SCD in either the RSG or control group. Immunocytochemical staining showed NGF infusion to LSG and RSG resulted in left and right ventricular sympathetic nerve sprouting and hyperinnervation, respectively. CONCLUSION: NGF infusion to the LSG in dogs with MI and CAVB resulted in increased QT interval and incidence of ventricular tachycardia, ventricular fibrillation, and SCD, whereas NGF infusion to the RSG shortened QT interval and reduced the incidence of ventricular tachycardia. These findings indicate that QT interval prolongation is causally related to the occurrence of ventricular arrhythmia in dogs with nerve sprouting, MI, and CAVB.

Animals↗
PubMed2001

Reflex sympathetic dystrophy with hidradenitis suppurativa exacerbation: a case report.

Reflex sympathetic dystrophy (RSD) or complex regional pain syndrome type 1, is characterized by spontaneous pain or allodynia and hyperalgesia disproportionate to the inciting event, multiperipheral nerve involvement, edema, vasomotor or sudomotor change, and possible loss of function. It has been described in relation to various insults, including a number of infectious and inflammatory conditions. We report a case of a patient who developed RSD 1 week after an exacerbation of hidradenitis suppurativa, a rare chronic inflammatory disease of apocrine sweat glands. The patient responded well to a combination of range-of-motion exercises, thermal modalities, and oral steroids. Hidradenitis suppurativa should be considered when searching for an etiology of new onset RSD.

Aged↗
PubMed2001

Endoscopic factors predisposing to rebleeding following endoscopic hemostasis in bleeding peptic ulcers.

BACKGROUND AND STUDY AIMS: Various clinical and endoscopic factors have been proposed and used as predictors of endoscopic treatment failure in bleeding peptic ulcers. Recently, several endoscopic factors have been considered to be more significant than various clinical factors, except for shock. Detailed knowledge of which endoscopic factors can be classified as predictors of rebleeding following endoscopic hemostasis is needed. This study describes newly defined endoscopic variables and evaluates their usefulness as predictors of endoscopic treatment failure. PATIENTS AND METHODS: Between January 1996 and April 1999, diagnostic and therapeutic endoscopies were carried out in 143 patients with active bleeding peptic ulcers. Nine clinical and eight endoscopic variables were studied. Endoscopic factors were classified by three types of stigmata bleeding, 14 locations, two ulcer sizes, three ulcer bases, three visible vessel colors, two ulcer depths, two margin shapes, and three endoscopic treatment methods (injection, hemoclipping, and combination). RESULTS: 36 patients experienced rebleeding (25.2 %), 11 patients needed operations (7.7 %) and five deaths occurred (3.5 %). In univariate analysis, rebleeding was significantly related to: i) presence of spurting activity (odds ratio [OR] = 4.91, P = 0.006), ii) ulcer size larger than 2 cm (OR = 2.78, P = 0.017); and iii) location in stomach (OR = 2.81, P = 0.026). Clinical variables including age, shock, and initial hemoglobin levels were not significantly related to rebleeding. In multiple logistic regression using selected significant variables, presence of spurting activity remained a significant independent predictor of rebleeding (adjusted OR = 6.48, P = 0.003). CONCLUSION: Our data support the hypothesis that endoscopic factors are more important than clinical ones when predicting rebleeding of peptic ulcers. Based on statistical analysis of risk factors, the ulcers most likely to rebleed after endoscopic therapy are those which are located in the stomach, are greater than 2 cm in diameter and exhibit oozing or spurting of blood.

Adolescent↗
PubMed2001

Genetic basis of sitosterolemia.

The molecular mechanisms regulating the amount of dietary cholesterol retained by the body, as well as the body's ability to exclude other dietary sterols selectively, are poorly understood. An average Western diet will contain approximately 250-500 mg of dietary cholesterol and approximately 200-400 mg of non-cholesterol sterols, of which plant sterols are the major constituents. Approximately 50-60% of dietary cholesterol is absorbed and retained by the normal human body, but less than 1% of the non-cholesterol sterols are retained. There thus exists a subtle mechanism that allows the body to distinguish between cholesterol and non-cholesterol sterols. In sitosterolemia, a rare autosomal recessive disorder, affected individuals hyperabsorb and retain not only cholesterol but also all other sterols, including plant and shellfish sterols from the intestine. Consequently, patients with this disease have very high levels of plant sterols in the plasma, and develop tendon and tuberous xanthomas, accelerated atherosclerosis, and premature coronary artery disease. The STSL locus has been mapped to human chromosome 2p21. Mutations in two tandem ABC genes, ABCG5 and ABCG8, encoding sterolin-1 and -2, respectively, are now known to be mutant in sitosterolemia. The identification of these genes should now lead to a better understanding of the molecular mechanism(s) governing the highly selective absorption and retention of cholesterol by the body. Indeed, it is the very existence of this disease that has given credence to the hypothesis that there is a molecular pathway that regulates dietary cholesterol absorption and sterol excretion by the body.

ATP-Binding Cassette Transporters↗
PubMed2001

Colonic motility abnormality in patients with irritable bowel syndrome exhibiting abdominal pain and diarrhea.

OBJECTIVES: Although colon dysmotility is recognized as a pathophysiological factor in irritable bowel syndrome (IBS), it has not been characterized. We have investigated motility patterns in IBS patients with abdominal pain and frequent defecation or diarrhea and in healthy volunteers. METHODS: A recording catheter that had six polyvinyl tubes with infusion ports was placed in the transverse, descending, and sigmoid colon under fluoroscopy. After 2-h basal recordings, motility responses to cholecystokinin octapeptide (CCK-8) and a meal were studied for 3 h. The motility index (MI) and number of high amplitude propagating contractions (HAPCs) in 10 IBS patients were compared with those of 10 controls. HAPCs were correlated with abdominal pain, and colon transit time using radio-opaque markers was determined. Using human colon muscle strips, the effect of CCK-8 on muscle contractions was also studied. RESULTS: The MI and mean number and peak amplitude of HAPCs in IBS patients were significantly greater than in controls. These abnormalities paralleled markedly shortened colonic transit time. Abdominal pain coincided with >90% of HAPCs. Dose-dependent muscle contraction by CCK-8 was profoundly suppressed both by loxiglumide and atropine. CONCLUSIONS: The dysmotility in this subset of IBS patients was characterized by significantly increased occurrences of powerful HAPCs that paralleled rapid colon transit and were accompanied by abdominal pain. Thus, it is suggested that this powerful contraction is one of the causes of abdominal pain. The action of CCK-8 seems to be mediated via the colon enteric nervous system.

Abdominal Pain↗
PubMed2001

Effects of diacetyl monoxime and cytochalasin D on ventricular fibrillation in swine right ventricles.

Whether or not the excitation-contraction (E-C) uncoupler diacetyl monoxime (DAM) and cytochalacin D (Cyto D) alter the ventricular fibrillation (VF) activation patterns is unclear. We recorded single cell action potentials and performed optical mapping in isolated perfused swine right ventricles (RV) at different concentrations of DAM and Cyto D. Increasing the concentration of DAM results in progressively shortened action potential duration (APD) measured to 90% repolarization, reduced the slope of the APD restitition curve, decreased Kolmogorov-Sinai entropy, and reduced the number of VF wave fronts. In all RVs, 15-20 mmol/l DAM converted VF to ventricular tachycardia (VT). The VF could be reinduced after the DAM was washed out. In comparison, Cyto D (10-40 micromol/l) has no effects on APD restitution curve or the dynamics of VF. The effects of DAM on VF are associated with a reduced number of wave fronts and dynamic complexities in VF. These results are compatible with the restitution hypothesis of VF and suggest that DAM may be unsuitable as an E-C uncoupler for optical mapping studies of VF in the swine RVs.

Action Potentials↗
PubMed2001

Patterns of wave break during ventricular fibrillation in isolated swine right ventricle.

Several different patterns of wave break have been described by mapping of the tissue surface during fibrillation. However, it is not clear whether these surface patterns are caused by multiple distinct mechanisms or by a single mechanism. To determine the mechanism by which wave breaks are generated during ventricular fibrillation, we conducted optical mapping studies and single cell transmembrane potential recording in six isolated swine right ventricles (RV). Among 763 episodes of wave break (0.75 times x s(-1) x cm(-2)), optical maps showed three patterns: 80% due to a wave front encountering the refractory wave back of another wave, 11.5% due to wave fronts passing perpendicular to each other, and 8.5% due to a new (target) wave arising just beyond the refractory tail of a previous wave. Computer simulations of scroll waves in three-dimensional tissue showed that these surface patterns could be attributed to two fundamental mechanisms: head-tail interactions and filament break. We conclude that during sustained ventricular fibrillation in swine RV, surface patterns of wave break are produced by two fundamental mechanisms: head-tail interaction between waves and filament break.

Action Potentials↗
PubMed2001

Enzyme-linked immunosorbent assay for screening the plasma residues of tetracycline antibiotics in pigs.

The recommended therapeutic doses of three kinds of tetracyclines, oxytetracycline (OTC, withdrawal period, 10 days), chlortetracycline (CTC, withdrawal period, 5 days) and tetracycline (TC, withdrawal period, 5 days), were each administered to a group of 15 pigs. Blood was sampled before drug administration and during the withdrawal period. The concentration of tetracyclines in plasma, determined by semi-quantitative ELISA, was compared with that of internal standard (10 ppb as oxytetracycline). The absorbance ratio of internal standard to sample (B/Bs) was employed as an index to determine the tissue residues in pigs. All 45 plasma samples from nontreated pigs showed negative in the residue of any of three tetracycline antibiotics. OTC was detected in plasma of pigs treated until the 8th day, CTC until the 4th day, and TC was detected until the 3rd day of its withdrawal period. The present study showed that the semi-quantitative ELISA easily be adopted in predicting tissue residues for tetracycline antibiotics in live pigs.

Animals↗
PubMed2001

Antimicrobial resistance surveillance of bacteria in 1999 in Korea with a special reference to resistance of enterococci to vancomycin and gram-negative bacilli to third generation cephalosporin, imipenem, and fluoroquinolone.

The trend of antimicrobial resistance of bacteria isolated from patients in 30 Korean hospitals in 1999 was analyzed with a particular attention to cefotaxime- or fluoroquinolone-resistant gram-negative bacilli, imipenem-resistant Pseudomonas aeruginosa, and vancomycin-resistant enterococci. Adequacy of susceptibility testing, and any change in the frequencies of isolated species were also analyzed. The results showed that only 20% and 30% of hospitals tested the piperacillin-tazobactam and cefoxitin susceptibility of Enterobacteriaceae, respectively, only 24% of hospitals the piperacillin-tazobactam susceptibility of P. aeruginosa, and 17% of hospitals the fusidic acid susceptibility of staphylococci. Among the isolates 26.3% were glucose-nonfermenting gram-negative bacilli, and 34.7% of Enterococcus were Enterococcus faecium. Slight decline of cefotaxime-resistance rate to 20% was noted in Klebsiella pneumoniae, while fluoroquinolone-resistance rate was 68% in Acinetobacter baumannii. The ceftazidime- and imipenem-resistance rates were 17% and 18%, respectively in P. aeruginosa. The vancomycin-resistance rate of E. faecium rose significantly to 15.1%, but the rates varied significantly depending on hospitals suggesting presence of different degree of selective pressure or nosocomial spread. In conclusion, the prevalence of imipenem-resistant P. aeruginosa and the increase of vancomycin-resistant E. faecium were the particularly worrisome phenomena observed in this study.

Anti-Bacterial Agents↗
PubMed2001

Frequencies of fetal chromosomal abnormalities at prenatal diagnosis: 10 years experiences in a single institution.

We present frequencies of fetal chromosomal abnormalities in 4,907 prenatal cytogenetic examinations at Samsung Cheil Hospital from 1988 to 1997 for 10 yr duration. Prenatal karyotypes were undertaken in 3,913 amniotic fluid samples, 800 chorionic villi samples, and 194 percutaneous umbilical blood samples. The frequency of fetal abnormal karyotypes was 3.1% (150 cases). Numerical chromosome abnormalities were 87 cases (1.8%) and structural aberrations of chromosomes were 63 cases (1.3%). In the numerical chromosomal abnormalities, the frequency of trisomy 21 was by far the highest (36 cases), followed by trisomy 18 in 22 cases and sex chromosome aneuploidies in 19 cases. In the structural chromosomal aberrations, 5 cases had the inversions in chromosome 2, 7, 17, and Y. Chromosomal deletions in 6 cases and additions in 4 cases were analysed. Of the remaining 47 translocation in abnormal fetuses, reciprocal translocation was in 26 cases and Robertsonian translocation in 21 cases. Among them, 41 cases were balanced translocation and 6 were unbalanced. Thirty five cases of translocation were inherited from one of the parents. Four had de novo chromosome rearrangements, and 8 cases were unknown.

Chromosome Aberrations↗
PubMed2001

What is the best method to diagnose Helicobacter infection in bleeding peptic ulcers?: a prospective trial.

BACKGROUND: It has been debated which diagnostic test should be preferred for the diagnosis of Helicobacter pylori (HP) in patients with peptic ulcer diseases. Several limitations are reported in bleeding peptic ulcers because of intragastric blood and possibility of changed numbers of organisms by medication. This study was designed to find out the best method for diagnosis of HP infection, in aspect of deciding the times of detection and the specific tests in bleeding peptic ulcers. METHODS: We prospectively examined histology, rapid urease test (CLO test), urea breath test (13C-UBT) and serology in HP diagnostics in 32 patients with bleeding peptic ulcers to detect HP infection. Each test was performed two times (four methods at first 24 hours and former three methods at 7th day after initial therapeutic endoscopy). We evaluated the sensitivity of each test, compared the two-times results and evaluated the effect of these tests to an outcome of endoscopic hemostasis. RESULTS: Diagnostic sensitivities of histology, CLO test, 13C-UBT and serology are 75%, 67.8%, 100% and 100% at first endoscopy, and 71.4%, 78.5%, 89.3% at 7th day endoscopy, respectively. Histologic study and CLO test had diagnostic limitation at emergent first endoscopy contrary to UBT (p < 0.01). Histologic study, CLO test and UBT have limitations at 7th day endoscopy. Only 3 patients (9.4%) rebled with subsequent complete endoscopic hemostasis and all diagnostic tests at initial endoscopy did not influence the outcome of hemostasis. CONCLUSION: First day histologic and CLO tests are inadequate methods in detecting HP infection in patients with bleeding peptic ulcers. 7-day histologic, CLO test and UBT have a low sensitivity. First-day UBT can be a standard test to diagnose HP infection in patients with bleeding peptic ulcers.

Biopsy, Needle↗
PubMed2001

Fine-mapping, mutation analyses, and structural mapping of cerebrotendinous xanthomatosis in U.S. pedigrees.

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder of bile acid biosynthesis. Clinically, CTX patients present with tendon xanthomas, juvenile cataracts, and progressive neurological dysfunction and can be diagnosed by the detection of elevated plasma cholestanol levels. CTX is caused by mutations affecting the sterol 27-hydroxylase gene (CYP27 ). CTX has been identified in a number of populations, but seems to have a higher prevalence in the Japanese, Sephardic Jewish, and Italian populations. We have assembled 12 previously unreported pedigrees from the United States. The CYP27 locus had been previously mapped to chromosome 2q33-qter. We performed linkage analyses and found no evidence of genetic heterogeneity. All CTX patients showed segregation with the CYP27 locus, and haplotype analysis and recombinant events allowed us to precisely map CYP27 to chromosome 2q35, between markers D2S1371 and D2S424. Twenty-three mutations were identified from 13 probands analyzed thus far; 11 were compound heterozygotes and 2 had homozygous mutations. Of these, five are novel mutations [Trp100Stop, Pro408Ser, Gln428Stop, a 10-base pair (bp) deletion in exon 1, and a 2-bp deletion in exon 6 of the CYP27 gene]. Three-dimensional structural modeling of sterol 27-hydroxylase showed that, while the majority of the missense mutations disrupt the heme-binding and adrenodoxin-binding domains critical for enzyme activity, two missense mutations (Arg94Trp/Gln and Lys226Arg) are clearly located outside these sites and may identify a potential substrate-binding or other protein contact site.

Adolescent↗
PubMed2001

Effects of nonylphenol, bisphenol A, and their mixture on the viviparous swordtail fish (Xiphophorus helleri).

A number of fish species have been used for studies on endocrine disrupting chemicals (EDCs). However, despite the widespread use of oviparous fish, relatively little attention has been given to viviparous species. This study investigated the effects of EDCs in a viviparous fish and examined the possible usefulness of the fish as an alternative model for the studies on EDCs. Swordtails (Xiphophorus helleri) were exposed to nonylphenol (NP), bisphenol A (BPA), and their mixture. Both short-term (3-d) and relatively long-term (60-d) exposures were carried out using adult male and 30-d-old juvenile fish, respectively. Following the short-term exposure, both NP and BPA caused vitellogenin mRNA expression. Flow cytometric analysis and terminal deoxynucleotidyl transferase assay on the testes of treated fish indicated reproductive damage. Histopathological analysis found degenerative and necrotic cells in seminiferous tubules following the exposure to 100 ppb NP. The testes with lesions were also associated with highly suppressed spermatogenesis. Following the long-term exposure, both NP and BPA exposures significantly affected the growth of swordtails. In all cases, the results showed that the mixture was always more potent than a single chemical and that swordtail fish can be a useful model for the study of endocrine disruptors.

Air Pollutants, Occupational↗
PubMed2001

Classic Kaposi sarcoma presenting as rapidly growing nodules.

Classic Kaposi sarcoma (KS) is a sporadic disease that usually affects persons older than 50 years, with a distinct male predominance. Although classic KS has a protracted, indolent course, there appears to be a rare disseminated fulminant type. This report describes a case of classic KS, presenting as a very rapid enlargement and dissemination of skin lesions, without evidence of human immunodeficiency virus (HIV) infection or involvement of other internal organs.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Oviductural carcinoma in B6C3F1 female mice exosed to 0.5 ppm ozone.

The toxicity and carcinogenecity of ozone was evaluated in B6C3F1 mice exposed to 0.5 ppm ozone via inhalation for 12 w, during which no ozone-related deaths occurred. Decreases in mean body weights of both genders exposed to ozone were sporadically seen, and mean absolute and relative weights of several organs from male and female groups receiving ozone were lower than those of respective air-control groups. No ozone-related increased neoplasm incidences were observed in most organs, including the lung; however, oviductural carcinomas were seen in the ozone-exposed females. Although ozone does not induce lung cancer under our experimental condition, it induces oviductural carcinomas in B6C3F1 mice.

Animals↗