Biomedical subjects

S Lee

Publications and source records attributed to S Lee.

At least 343 records · Page 19Linked to original sources

PubMed2001

Inhibition of rac1 reduces PDGF-induced reactive oxygen species and proliferation in vascular smooth muscle cells.

In vascular smooth muscle cells, reactive oxygen species (ROS) were known to mediate platelet-derived growth factor (PDGF)-induced cell proliferation and NADH/NADPH oxidase is the major source of ROS. NADH/NADPH oxidase is controlled by rac1 in non-phagocytic cells. In this study, we examined whether the inhibition of rac1 by adenoviral-mediated gene transfer of a dominant negative rac1 gene product (Ad.N17rac1) could reduce the proliferation of rat aortic vascular smooth muscle cells (RASMC) stimulated by PDGF via decreasing intracellular ROS. RASMC were stimulated by PDGF (80 ng/mL) with or without N-acetylcysteine 1 mM or infected with 100 mutiplicity of infection of Ad.N17rac1. Intracellular ROS levels were measured at 12 hr using carboxyl-2', 7'-dichlorodihydrofluorescein diacetate confocal microscopy. At 72 hr, cellular proliferation was evaluated by cell number counting and XTT assay. Compared with control, ROS levels were increased by 2-folds by PDGF. NAC and Ad.N17rac1 inhibited PDGF-induced increase of ROS by 77% and 65%, respectively. Cell number was increased by PDGF by 1.6-folds compared with control. NAC and Ad.N17rac1 inhibited PDGF-induced cellular growth by 45% and 87%, respectively. XTT assay also showed similar results. We concluded that inhibition of rac1 in RASMCs could reduce intracellular ROS levels and cellular proliferation induced by PDGF.

Adenoviridae↗

PubMed2001

Association of chronic hepatitis C virus infection and diabetes mellitus in Korean patients.

BACKGROUND: It has been suggested that chronic hepatitis C virus (HCV) infection is associated with diabetes. The aim of this study was to establish a potential relationship between chronic HCV infection and diabetes mellitus in Korean patients. METHODS: We performed a prospective analysis of 404 patients with chronic viral hepatitis or liver cirrhosis who visited our hospital and analyzed whether age, sex, body mass index, alcohol consumption, hepatitis B virus (HBV) infection, HCV infection and cirrhosis were associated with diabetes. We also enrolled 627 diabetic patients and the seroprevalence of HBV surface antigen (HBsAg) and anti-HCV was determined. RESULTS: Diabetes was observed more frequently in individuals with HCV infected chronic liver disease (24.0%) than in those with HBV infected (10.4%) (p < 0.05). Univariate analyses revealed that age, alcohol consumption and HCV infection were significant independent predictors for diabetes. The mean age of the patients with HCV infected chronic liver disease was higher than that of HBV infected (56 +/- 16 vs 44 +/- 13, p < 0.05). The prevalence of diabetes in HCV infected group was higher than that in HBV infected group in the age of 41-60 (p < 0.05). In diabetic group, the seroprevalence of HBsAg positivity was 4.5% and that of anti-HCV was 2.1%. CONCLUSION: Our study demonstrates an association between diabetes and chronic HCV infection in Korean patients. The prevalence of diabetes in patients with HCV infected chronic liver disease is higher than that in those with HBV infected. Age and alcohol consumption are another risk factor for diabetes in patients with chronic viral liver disease.

Adult↗

PubMed2001

Clinical features of vivax malaria.

Plasmodium vivax malaria reemerged in the Republic of Korea in 1993 near the Demilitarized Zone (DMZ). We reviewed clinical features of 101 symptomatic patients with vivax malaria. Of the patients, 77 patients (76.3%) were veterans who had served near the DMZ; their median age was 23 years. The duration of the minimum latent period was > 6 months in 66.2% (51 of 77) of the patients (median, 278 days). Tertian fever developed in 69 patients (68.3%). Severe thrombocytopenia with platelet counts < 60,000/microL was common (29.6% of patients). The parasite densities ranged 32-52,127 parasites per microliter of blood (geometric mean, 1,287). The only complication was a splenic rupture in one patient. All patients responded promptly to chloroquine therapy. Our data suggest that the clinical features of reemerging vivax malaria may be similar to those of Korean vivax malaria reported in the past.

Adolescent↗

PubMed2001

A phylogenetic analysis of Prunus and the Amygdaloideae (Rosaceae) using ITS sequences of nuclear ribosomal DNA.

The economically important plum or cherry genus (PRUNUS:) and the subfamily Amygdaloideae of the Rosaceae have a controversial taxonomic history due to the lack of a phylogenetic framework. Phylogenetic analysis using the ITS sequences of nuclear ribosomal DNA (nrDNA) was conducted to construct the evolutionary history and evaluate the historical classifications of PRUNUS: and the Amygdaloideae. The analyses suggest two major groups within the Amygdaloideae: (1) PRUNUS: s.l. (sensu lato) and MADDENIA:, and (2) EXOCHORDA:, Oemleria, and PRINSEPIA: The ITS phylogeny supports the recent treatment of including EXOCHORDA: (formerly in the Spiraeoideae) in the Amygdaloideae. MADDENIA: is found to be nested within PRUNUS: s.l. in the parsimony and distance analyses, but basal to PRUNUS: s.l. in the maximum likelihood analysis. Within PRUNUS:, two major groups are recognizable: (1) the AMYGDALUS:-PRUNUS: group, and (2) the CERASUS:-LAUROCERASUS:-PADUS: group. The clades in the ITS phylogeny are not congruent with most subgeneric groups in the widely used classification of PRUNUS: by Rehder. A broadly defined PRUNUS: is supported.

Journal Article↗

PubMed2001

Effect of repeated exposure to alcohol on the response of the hypothalamic-pituitary-adrenal axis of the rat: II. Role of the length and regimen of alcohol treatment.

BACKGROUND: Prior exposure to alcohol alters the adrenocorticotropin hormone (ACTH) response to a second drug challenge administered several days later. We used three models of alcohol treatment to investigate the mechanisms that may be involved in this phenomenon. METHODS: Adult male rats were exposed to alcohol vapors daily for 3 days (4-4.5 hr/day) and then were exposed to shocks or an intragastric injection of alcohol 7 days later (group A); were injected daily with alcohol (4.5 g/kg intragastrically) for 3 days and then exposed to shocks or an intragastric injection of alcohol 7 days later (group B); or were exposed to alcohol vapors for 6 days and exposed to shocks or an intragastric injection 24 hr later (group C). Control animals were not exposed to the vapors or received the appropriate vehicle. RESULTS: Compared with animals administered the vehicle, rats of groups A and B that had been exposed to alcohol all exhibited a significantly decreased ACTH response to a second drug challenge. In contrast, their ACTH response to footshocks was statistically comparable to that of vehicle-pretreated animals. Rats of group C that had been exposed to alcohol for 6 days also showed decreased ACTH release when injected with alcohol 7 days later while responding normally to shocks. Measurement of anterior pituitary pro-opiomelanocortin indicated that alcohol pretreatment had produced a 54% increase of these transcripts in group C and a 27% decrease in group A. There were no changes in pituitary receptors type 1 for corticotropin-releasing factor (CRFR1) in any of the groups. CONCLUSION: Regardless of whether they are delivered shortly before an acute alcohol injection or several days earlier, alcohol vapors or injections interfere with the ACTH response to the drug but not to shocks. Our results also suggest that changes in ACTH responses may not be correlated directly with small changes in pituitary pro-opiomelanocortin or CRFR1 mRNA levels.

Adrenocorticotropic Hormone↗

PubMed2001

Effect of repeated exposure to alcohol on the response of the hypothalamic-pituitary-adrenal axis of the rat: I. Role of changes in hypothalamic neuronal activity.

BACKGROUND: Prior (3-12 days) injection of alcohol significantly blunts the response of the hypothalamic-pituitary-adrenal (HPA) axis to a second drug challenge without measurably altering responses to other stressors. We therefore determined whether adaptation in hypothalamic neurons underlies this decreased activity. METHODS: Adult male rats were administered alcohol (4.5 g/kg intragastrically) or vehicle daily for three consecutive days and then were challenged with the vehicle or alcohol 7 days later. Levels of adrenocorticotropin hormone (ACTH) in the circulation, corticotropin-releasing factor (CRF), CRF receptors type 1 (CRFR1) and vasopressin (VP) transcripts in the paraventricular nucleus (PVN) of the hypothalamus, and CRF/VP peptide in the median eminence were measured. RESULTS: Resting PVN levels of CRF, CRFR1, and VP were comparable in all animals on day 7 of recovery, whereas CRF and VP stores in the external zone of the median eminence were decreased in animals previously exposed to alcohol. After the acute alcohol challenge on day 7, rats previously exposed to the drug exhibited a significant (p < 0.01) dampening of their PVN CRF and CRFR1, but not VP neuronal response, compared with vehicle-pretreated rats. CONCLUSION: Blunted neuronal activity of PVN CRF neurons may be responsible for the decreased ACTH response that we previously reported in rats that had been injected with alcohol several days earlier. In addition, and despite comparable PVN VP transcript levels, the lower levels of this peptide in the median eminence also may participate in the blunted ACTH response that we observed.

Adrenocorticotropic Hormone↗

PubMed2001

Mice that lack corticotropin-releasing factor (CRF) receptors type 1 show a blunted ACTH response to acute alcohol despite up-regulated constitutive hypothalamic CRF gene expression.

BACKGROUND: The purpose of this work was to determine the influence of acute alcohol treatment, injected intraperitoneally, on the hypothalamic-pituitary-adrenal axis of mice that lack type 1 receptor for corticotropin-releasing factor (CRFR1). METHODS: CRFR1-deficient (CRFR1-/-), heterozygous (CRFR1+/-), and wild-type (CRFR1+/+) mice were generated and maintained under standard conditions. Homozygous, heterozygous, and wild-type offspring were identified by polymerase chain reaction analysis of tail DNA. Experiments were performed on 9- to 16-week-old male and female mice. All blood samples were obtained by rapid decapitation of conscious mice conducted between 10 AM-12 PM. Blood sample collection was completed within 20 to 30 sec of disturbing the animals, and all samples were terminal. Preliminary experiments were conducted to determine the time-course of the ACTH and hypothalamic responses to alcohol in all three groups of mice, and a single time point (30 min and 2 hr, respectively), corresponding to peak responses, was chosen to measure the corresponding parameters in all subsequent studies. RESULTS: In vehicle-injected animals, basal ACTH and corticosterone levels were statistically comparable in heterozygotes and mice with a null allele for the CRFR1 gene, although values of this latter hormone were slightly lower in the mutants. Alcohol (4.0 g/kg) elicited the expected significant (p < 0.01) increase in plasma ACTH and corticosterone levels in heterozygous mice. These responses were virtually abolished or markedly decreased, respectively, in CRFR1-deficient animals. As previously reported, constitutive CRF mRNA levels were elevated in the paraventricular nucleus (PVN) of the hypothalamus in mice that lacked CRFR1, compared to wild-type control mice. Interestingly, this was not the case for transcripts of the immediate early gene NGFI-B. When measured 2 hr after alcohol, PVN NGFI-B gene expression was significantly (p < 0.01) increased in both control and mutant mice, as were CRF mRNA levels in mutant mice, but the hypothalamic responses of the mutants were larger (p < 0.01) than those of the control mice. This difference may be due, at least in part, to the lack of steroid feedback in the mutants. CONCLUSION: These results indicate that although the intraperitoneal injection of alcohol remains capable of eliciting PVN CRF neuronal activation in mice that lack CRFR1, the ACTH and corticosterone responses are significantly blunted, a phenomenon believed to be due to the lack of CRFR1 in the pituitary of these animals.

Adrenocorticotropic Hormone↗

PubMed2001

Role of basement membrane in tumor growth and metastasis.

The basement membrane is a thin extracellular matrix produced by epithelial and endothelial cells. It is biologically active for normal epithelial cell differentiation. Basement membrane promotes the growth of tumor cells in vitro and in vivo when coinjected. Laminin, the major biologically active component, also increases tumor growth and the malignant phenotype by promoting increased cell growth and protease activity. Using systematic peptide screening with synthetic peptides covering the entire laminin molecule, several active sites in laminin have been identified that regulate tumor growth and metastasis.

Basement Membrane↗

PubMed2001

Beta-blockers to reduce mortality in patients with systolic dysfunction: a meta-analysis.

OBJECTIVE: The researchers reviewed published clinical trials and performed a meta-analysis to assess if therapy with adrenergic beta-antagonists (beta-blockers) reduces the risk of mortality in patients with systolic dysfunction. STUDY DESIGN: A systematic review was performed with meta-analysis where appropriate. Clinical trials were reviewed with respect to the quality of the research methods, including patient population and end points. Two independent reviewers calculated relative risk, relative risk reduction, absolute risk reduction, and number needed to treat for the total mortality end point reported in each trial. A meta-analysis was performed. DATA SOURCES: The study team searched pertinent indexing services and references from published articles for relevant literature. The selected clinical trials were randomized, double-blinded, and controlled, and included patients with systolic heart failure. Mortality was assessed as a primary or secondary end point. OUTCOMES MEASURED: The primary outcome was mortality. RESULTS: Statistically and clinically significant improvement, including a statistically significant reduction in mortality, has been noted in patients receiving therapy with either bisoprolol, carvedilol, or metoprolol. Pooled analysis revealed a statistically significant reduction in the risk of total mortality (odds ratio [OR]MH=0.66; 95% confidence interval [CI], 0.58-0.75) and sudden death (ORMH=0.61; 95% CI, 0.5-0.75) for patients receiving beta-blocker therapy. CONCLUSIONS: All patients with New York Heart Association class II and III heart failure should receive beta-blocker therapy with bisoprolol, carvedilol, or metoprolol. Additional clinical trials are ongoing and will provide further data on which patients receive the greatest benefit from therapy and which beta-blocker may be preferred.

Adrenergic beta-Antagonists↗

PubMed2001

Confirmation that offspring from families with alcohol-dependent individuals have greater hypothalamic-pituitary-adrenal axis activation induced by naloxone compared with offspring without a family history of alcohol dependence.

BACKGROUND: This study was designed to confirm our previous findings that nonalcoholic offspring from families with alcohol-dependent individuals have greater hypothalamic-pituitary-adrenal axis activation induced by opioid blockade compared with nonalcoholic subjects without a family history of alcohol dependence. METHODS: Sixty-four nonalcoholic subjects aged 18 to 25 years were enrolled in the protocol. Twenty-seven subjects were offspring from families with alcohol dependence and were designated as family history-positive subjects (FHP). Thirty-seven subjects were biological offspring of non-alcohol-dependent parents and were designated as family history-negative subjects (FHN). Subjects received naloxone hydrochloride (0, 50, 125, 375, and 500 microg/kg) in double-blind, randomized order; adrenocorticotropin (ACTH) and cortisol were monitored over 120 min. RESULTS: No hormone differences at baseline or during placebo administration were identified between FHP and FHN subjects. FHP subjects had greater ACTH and cortisol response to opioid receptor blockade induced by naloxone hydrochloride compared with FHN subjects. CONCLUSIONS: These observations confirm previous findings that differences in ACTH and cortisol dynamics between FHP and FHN subjects can be unmasked by opioid receptor blockade.

Adolescent↗

PubMed2001

Rapid allergen delivery with photomechanical waves for inducing allergic skin reactions in the hairless guinea pig animal model.

BACKGROUND: Patch testing is the confirmatory procedure for allergic contact dermatitis. The test requires the application of chemicals under occlusion for approximately 48 hours to maximize penetration, although it can also produce irritation. Photomechanical waves (PW) have been shown to render the stratum corneum transiently permeable and facilitate the delivery of macromolecules into the epidermis. This alternative might reduce prolonged occlusion of the skin to minimize irritancy, while retaining the sensitivity of the test. OBJECTIVE: PW was used to facilitate the delivery of an allergen into the skin in vivo. METHODS: The allergic skin reaction using PW delivery was compared with 5-minute and 21-hour occlusion in a sensitized hairless albino guinea pig model. The pigs were sensitized by intradermal injection of (0.01%) dinitrochlorobenzene (DNCB) and topical administration (0.1%, 1 week later) of the hapten. One month later, testing for the allergic response was performed by the administration with PW of 10 microL of 0.1% DNCB. RESULTS: Our results show that there was an allergic reaction for the 24 hour occlusion or PW delivery of the antigen. In contrast, no response was observed for the 5-minute occlusion with the antigen. CONCLUSION: The rapid delivery of antigens with PW can improve the test for the diagnosis of contact dermatitis.

Allergens↗

PubMed2001

High-throughput genomic and proteomic analysis using microarray technology.

BACKGROUND: High-density microarrays are ideally suited for analyzing thousands of genes against a small number of samples. The next step in the discovery process is to take the resulting genes of interest and rapidly screen them against thousands of patient samples, tissues, or cell lines to further investigate their involvement in disease risk or the response to medication. METHODS: We used a microarray technology platform for both single-nucleotide polymorphisms (SNPs) and protein expression. Each microarray contains up to 250 elements that can be customized for each application. Slides contained either a 16- or 96-microarray format (4000-24,000 elements per slide), allowing the corresponding number of samples to be rapidly processed in parallel. RESULTS: Results for SNP genotyping and protein profiling agreed with results of restriction fragment length polymorphism (RFLP) analysis or ELISA, respectively. Genotyping analyses, using the microarray technology, on large sample sets over multiple polymorphisms in the NAT2 gene were in full agreement with traditional methodologies, such as sequencing and RFLP analysis. The multiplexed protein microarray had correlation coefficients of 0.82-0.99 (depending on analyte) compared with ELISAs. CONCLUSIONS: The integrated microarray technology platform is adaptable and versatile, while offering the high-throughput capabilities needed for drug development and discovery applications.

Arylamine N-Acetyltransferase↗

PubMed2001

MRP8, a new member of ABC transporter superfamily, identified by EST database mining and gene prediction program, is highly expressed in breast cancer.

BACKGROUND: With the completion of the human draft genome sequence, efforts are now devoted to identifying new genes. We have developed a computer-based strategy that utilizes the EST database to identify new genes that could be targets for the immunotherapy of cancer or could be involved in the multistep process of cancer. MATERIALS AND METHODS: Utilizing our computer-based screening strategy, we identified a cluster of expressed sequence tags (ESTs) that are highly expressed in breast cancer. Northern blot and reverse transcriptase polymerase chain reaction (RT-PCR) analyses demonstrated the tissue specificity of the computer-generated cluster and comparison with the human genome sequence assisted in isolating a full-length cDNA clone. RESULTS: We identified a new gene that is highly expressed in breast cancer. This gene is expressed at moderate levels in normal breast and testis and at very low levels in liver, brain, and placenta. The gene has two major transcripts of 4.5 kb and 4.1 kb. The 4.5-kb transcript is very abundant in breast cancer, and has an open reading frame of 1382 amino acids. The predicted protein sequence of the 4.5-kb transcript reveals that it has high homology with MRP5, a member of multidrug resistant-associated protein family (MRP). There are seven reported members in the MRP family; we designate this gene as MRP8 (ABCC11). The 4.5-kb MRP8 transcript consists of 31 exons and is located in a genomic region of over 80.4 kb on chromosome 16q12.1. The smaller 4.1-kb transcript of MRP8 is found in testis and may initiate within intron 6 of the gene. CONCLUSION: The selective expression of MRP8 (ABCC11), a new member of ATP-binding cassette transporter superfamily could be a molecular target for the treatment of breast cancer.

ATP-Binding Cassette Transporters↗

PubMed2001

Developing CD-ROM based multimedia digital textbook of 'San-Yin-Jiao(SP-6) pressure for reducing the labor pain and shortening the labor time'.

The computer-based textbook is a new educational tool that promises to play a prominent role in the coming years. Classical instructional technologies, such as video, stills, audio files and computer programs with a textbook orientation, have been merged into one multimedia computer system and have created additional opportunities for learning in medical, dental and nursing education. The authors developed a hypermedia textbook of â San-Yin-Jiao pressure for reducing the labor pain and shortening the labor time' using a personal computer with hypermedia software that contains texts, images, videos, audios and literature citations. The target population of this educational CD-ROM would be nurse-midwives, clinical nurses working for the obstetric units, and faculty members who teach the Maternity and Women's Health Nursing. Valuable and practical experiences were obtained and shared.

Acupressure↗

PubMed2001

Characterization of the selectivity and mechanism of cytochrome P450 inhibition by dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybiphenyl-2,2'-dicarboxylate.

In vitro studies with human liver microsomes and cytochrome P450 (P450) prototype substrates were performed to characterize the selectivity and mechanism of inhibition of P450 by dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybiphenyl-2,2'-dicarboxylate (DDB). DDB was found to be a strong inhibitor of testosterone 6beta-hydroxylation activity (CYP3A4) with a K(i) value of 0.27 +/- 0.21 microM. At higher concentrations, DDB marginally inhibited caffeine N(3)-demethylation (CYP1A2), diclofenac 4'-hydroxylation (CYP2C9), and dextromethorphan O-demethylation (CYP2D6) activities, but this compound had no effect on CYP2A6-, CYP2C19-, and CYP2E1-mediated reactions. Spectral analysis indicated that the formation of metabolite-P450 complex having absorbance at 456 nm was concentration-dependent; 5 to 33% of the total P450 was complexed in rat and human liver microsomes after a 5-min incubation with DDB. In addition, microsomal incubations with DDB in the presence of NADPH resulted in a loss of spectral P450 content, which was restored after adding K(3)Fe(CN)(6). This complex formation resulted in a time-dependent loss of CYP3A-catalyzed marker activity (testosterone 6beta-hydroxylation) in human liver microsomes. The inhibition was only partially restored upon dialysis. These results collectively suggest that formation of a metabolite-CYP3A complex with DDB was responsible for the CYP3A-selective time-dependent loss of catalytic function of CYP3A.

Animals↗

PubMed2001

Laboratory partnership with the Medical Devices Agency.

To improve the quality of the information and advice provided to the Health Service, the Medical Devices Agency (MDA) is actively seeking to increase the number of reports from hospital laboratories. The Medical Devices Agency relies heavily on laboratory reports of problems with in vitro diagnostic medical devices to investigate and take action where necessary. Laboratories are encouraged to report all suspected adverse incidents to the MDA.

Adverse Drug Reaction Reporting Systems↗

PubMed2001

A decade of interdisciplinary care.

A decade of organizing, implementing, and evaluating interdisciplinary care teams at St Luke's Regional Medical Center has reinforced the value of developing and maintaining clinical and nonclinical competencies. The value of consensus in task delegation cannot be overemphasized. Unit directors have expanded their scope of responsibility and must remain vigilant to avoid fragmentation of care in an interdisciplinary team delivery system.

Humans↗

PubMed2001

Putting a face on poverty--a tale of two counties.

Disparities in social and economic status create a wall between the well and well-off and those living on the other side of town: the poor, the chronically ill, and the dying. In some cases, the needy to whom we turn a blind eye, those who need healthcare the most, live next door to us or across the street, only a zip code away. The case studies presented in this article draw attention to these members of our community and the imperfections in our present system.

Delivery of Health Care↗