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Biomedical subjects

C H Lee

Publications and source records attributed to C H Lee.

At least 73 records · Page 4Linked to original sources
PubMed2002

Reference ranges and factors affecting the human corticotropin-releasing hormone test in preterm, very low birth weight infants.

This prospective study aims to investigate the factors that influence the human CRH (hCRH) test and to provide reference ranges for plasma corticotropin (ACTH) and serum cortisol concentrations of the stimulation test in preterm, very low birth weight (VLBW) infants. Two hundred twenty-six hCRH tests were performed on 137 VLBW infants at d 7 and 14 of life. Plasma ACTH did not differ significantly between infants whose mothers did not receive antenatal corticosteroids (group 1) and those whose mothers received one or two doses (group 2) or more than two doses (group 3) of the drug. However, plasma ACTH levels at d 7 were found to be significantly higher in infants with severe lung disease who required intermittent positive-pressure ventilation (IPPV) or high-frequency oscillation ventilation (HFOV), compared with those who had milder pulmonary disease and did not require mechanical ventilation or needed only continuous positive airway pressure (CPAP) support (P < 0.011). A significantly higher rate of increase in plasma ACTH concentration at d 7 was also observed in infants whose mothers suffered from antepartum hemorrhage (P < 0.016). In contrast, infants in group 2 had significantly lower serum cortisol, compared with group 1 infants (P < 0.05), whereas group 3 infants did not have serum cortisol levels significantly different from those of patients in group 1 or 2. Significant positive correlation between serum cortisol at d 7 and the time interval between the last dose of antenatal dexamethasone and delivery was also observed in group 3 infants (r > 0.33, P < 0.045). In addition, infants who required IPPV or HFOV had significantly lower serum cortisol at d 7 (P < 0.0001), but this pattern of cortisol response was reversed on d 14, with infants requiring IPPV or HFOV having significantly higher serum cortisol (P < 0.036). The reference ranges for plasma ACTH and serum cortisol concentrations of the hCRH test at d 7 and 14 were also provided for group 1 and group 2 infants. This study demonstrates that even one or two doses of antenatal corticosteroids cause adrenal suppression in VLBW infants. Maternal antepartum hemorrhage also influences the pituitary response of preterm newborns in the first week of life. The change in the pattern of cortisol response in sick ventilated (IPPV or HFOV) infants during the first 2 wk of life suggests that a proportion of preterm infants may have inadequate adrenal response to stress in early postnatal life, but it is likely that rapid adaptation of the hypothalamic-pituitary-adrenal axis results in enhanced and more appropriate cortisol response by d 14. The percentile distribution of plasma ACTH and serum cortisol responses provides useful statistical reference data for interpretation of the hCRH test in VLBW infants and may also assist in facilitating the use of corticosteroids replacement therapy in cases with clinical manifestations suggestive of adrenal insufficiency.

Adrenal Cortex Hormones↗
PubMed2002

Comparing fasting plasma glucose against two-hour post-load glucose concentrations for the diagnosis of diabetes mellitus and glucose intolerance in Singaporean hospital patients.

INTRODUCTION: Several studies have assessed the impact of the 1997 American Diabetes Association (ADA) recommendation, of using fasting plasma glucose (FPG) concentration, to diagnose diabetes mellitus in population-based cohorts. However, data concerning the impact of this recommendation in the hospital setting are limited. As the performance characteristics of diagnostic tests vary depending on the prevalence of diabetes in the population studied, we have examined the clinical impact of adopting the ADA recommendations in comparison to the traditional 2-hour post-load glucose (2HPG) concentration used by the World Health Organisation (WHO) in diagnosing diabetes and other categories of glucose intolerance in Singaporean hospital patients. MATERIALS AND METHODS: We analysed the results of the standard 75 g oral glucose tolerance test (OGTT) performed on 625 patients in our hospital from 1994 to 1999. RESULTS: The prevalence of diabetes amongst these 625 patients was 36.8% (230) based on the ADA recommendation of using FPG, 42.8% (263) on using the 2HPG and 52.0% (325) on using the full 1998 WHO criteria. The degree of agreement (kappa) in establishing the diagnosis of diabetes between the FPG and 2HPG cut-offs was 0.48. Ninety-five (15.2%) individuals had diabetes based on the 2HPG alone, 62 (9.9%) based on the FPG alone and 168 (26.9%) based on both the FPG and 2HPG. Eighty-six (13.8%) individuals had impaired fasting glucose (IFG) and 123 (19.7%) had impaired glucose tolerance (IGT). The kappa-value between IFG and IGT was 0.08. CONCLUSION: Fasting plasma glucose concentration was an inadequate parameter in diagnosing diabetes and intermediate categories of glucose intolerance in our cohort of subjects. Our findings suggest that the OGTT remains an important diagnostic tool for classifying glucose tolerance in our hospital patients.

Adolescent↗
PubMed2002

Sirolimus eluting stent in the treatment of atherosclerosis coronary artery disease.

Stent implantation represents the most commonly performed percutaneous coronary intervention nowadays. However, instent restenosis due to exaggerated neointimal hyperplasia remains a problem to overcome. Neointimal hyperplasia is a vascular response to stent injury; it mainly consists of smooth muscle cells proliferation. The underlying molecular mechanisms of restenosis were explained in this review article. Recently, drug-eluting stent has been proposed as a potential method to prevent instent restenosis. Animal studies have confirmed safety and efficacy of sirolimus-eluting stent implantation in vivo. The FIM trial, which was the first clinical study on sirolimus-eluting stent in de novo lesions, has shown an astonishing 0% restenosis rate. The RAVEL trial was the first prospective, double-blind, multi-center trial that randomized 238 patients at 19 institutions with de novo lesions into sirolimus-eluting versus bare Bx velocity stent. Six-month binary restenosis rate in the sirolimus-group was again 0% compared to 26.6% in the control group. Angiographic late loss and major cardiac event were also significantly lower in the sirolimus-group. The SIRIUS trial is an ongoing study conducted in 53 US centers that randomized 1100 patients with de novo lesion into sirolimus-eluting and bare stents. Preliminary results also showed a significant reduction in binary restenosis, late loss and repeat revascularization rates. Apart from de novo lesions, early experience of sirolimus-eluting stent implantation for instent restenosis in non-randomized study was also promising, achieving a single-digit repeat restenosis rate. As compare with standard coronary stent, a sirolimus-eluting stent shows considerable promise for the prevention of neointimal proliferation, restenosis and associated clinical events.

Angioplasty, Balloon, Coronary↗
PubMed2002

A proposed referral centre based on HL7/XML.

With the growth of the Inteernet, hospitals have also applied HL7 (Health Level Seven) to exchange data between them. The referral system is identified as an appropriate application system. The effect of referral is to transfer the patient to a suitable hospital in a timely fashion, and to arrange appropriate treatment for the patient. Taking advantage of the Internet to exchange referral data can, not only accelerate the process of patient referral, but also avoid the unnecessary repeat examinations to decrease the waste of medical resources. This article builds up a referral-related message according to the HL7 standard, and develops a referral centre using the Internet environment, making use of XML (eXtensible Markup Language) standard to transform the referral-related data to XML format and exchange referral data between platforms. This electronic referral mechanism is expected to offer other hospitals experience of improved referral practice.

Access to Information↗
PubMed2001

Synthesis of substituted-(l)-tryptophanols from an enantiomerically pure aziridine-2-methanol.

Enantiomerically pure (l)-tryptophanol (5) was synthesized from 4(R)-iodomethyl-2-oxazolidinone (2) and indolylmagnesium bromide in three steps (52% overall yield). Using this procedure, we also prepared various tryptophanols with substituent(s) on the indole ring. Furthermore, optically active 4(R)-iodomethyl-2-oxazolidinone was readily prepared from an enantiomerically pure aziridine-2(S)-methanol in high yield. [reaction: see text]

Journal Article↗
PubMed2001

Two inv dup(15) chromosomes in a woman with repeated abortions.

A 40-year-old, phenotypically normal woman, with a history of two repeated abortions and no child, had two additional, small, bisatellited, and apparently metacentric chromosomes. Various banding and microsatellite analyses indicated that the additional chromosomes were inv dup(15)(q11q11) without the Prader-Willi/Angelman syndromes critical region, and therefore without phenotypic effects. Her father had a single, identical additional inv dup(15) chromosome. Her husband was chromosomally normal, but sperm analysis indicated a reduced motility and a reduced frequency of morphologically normal sperm. In view of these findings, it was deduced that the inv dup(15) chromosome in the father was transmitted in duplicate to the woman. Individuals with two additional inv dup(15) chromosomes in the literature were reviewed, and possible correlation of the two additional inv dup(15) chromosomes in the woman and her repeated abortions was discussed.

Abortion, Spontaneous↗
PubMed2001

Potentiation of cadmium-induced cytotoxicity by sulfur amino acid deprivation through activation of extracellular signal-regulated kinase1/2 (ERK1/2) in conjunction with p38 kinase or c-jun N-terminal kinase (JNK). Complete inhibition of the potentiated toxicity by U0126 an ERK1/2 and p38 kinase inhibitor.

The mechanisms of cadmium-induced toxicity may include oxidative stress, altered redox homeostasis, and injuries to organelles. The current study was designed to study the effect of decreased cellular glutathione (GSH) content by sulfur amino acid deprivation on cadmium toxicity and to identify the signaling pathways responsible for the cytotoxicity. GSH content was increased by cadmium in H4IIE cells prior to cell death, which was prevented by excess GSH or cysteine. Cell viability, however, was not improved by GSH or cysteine complexation of cadmium. Cadmium-induced cytotoxicity was 40-fold potentiated in cells with decreased GSH by sulfur amino acid deprivation. Cadmium in combination with decreased GSH markedly increased apoptotic cell death. Mitogen-activated protein kinases including extracellular signal-regulated kinase 1/2, p38 kinase and c-Jun N-terminal kinase (JNK) were all activated 1-12 hr after sulfur amino acid deprivation. U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene), which inhibited activation of extracellular signal-regulated kinase1/2 and p38 kinase in cells under sulfur amino acid deprivation, completely prevented potentiation in Cd-induced cytotoxicity and apoptosis. Potentiation of cadmium toxicity by sulfur amino acid deprivation was prevented in part by either PD98059 or SB203580, or in cells stably expressing dominant negative mutant of JNK1, and to greater extents by PD98059 in combination with either SB203580 or JNK1(-) transfection. These results demonstrated that decreased cellular GSH content potentiated cytotoxicity induced by cadmium at the level of human exposure, and that the potentiation of cytotoxicity resulted from activation of extracellular signal-regulated kinase1/2 in conjunction with p38 kinase or JNK.

Amino Acids↗
PubMed2001

Drosophila LAR regulates R1-R6 and R7 target specificity in the visual system.

Different classes of photoreceptor neurons (R cells) in the Drosophila compound eye connect to specific targets in the optic lobe. Using a behavioral screen, we identified LAR, a receptor tyrosine phosphatase, as being required for R cell target specificity. In LAR mutant mosaic eyes, R1-R6 cells target to the lamina correctly, but fail to choose the correct pattern of target neurons. Although mutant R7 axons initially project to the correct layer of the medulla, they retract into inappropriate layers. Using single cell mosaics, we demonstrate that LAR controls targeting of R1-R6 and R7 in a cell-autonomous fashion. The phenotypes of LAR mutant R cells are strikingly similar to those seen in N-cadherin mutants.

Animals↗
PubMed2001

Effect of water activity and immobilization on fatty acid selectivity for esterification reactions mediated by lipases.

The effect of water activity (a(w)) and immobilization on fatty acid (FA) selectivity of Burkholderia (formerly Pseudomonas) cepacia, Rhizomucor miehei, Candida antarctica (type B), and Candida rugosa lipases in esterification reactions was determined. Studies were based on measuring ester formation in multicompetitive reaction mixtures containing either the homologous series of even carbon number n-chain saturated FA (C4-C18) or a series of n-chain (un)saturated FA (C18:X, where X = 0-3 double bonds) as cosubstrates with 1,3-propanediol in ter-butyl methyl ether at a(w) of 0.19, 0.69, and 0.90. Activity and FA selectively patterns were similar for free and Celite-adsorbed lipases in response to changes in a(w'), although specific effects were observed for selectivity of B. cepacia and C. rugosa lipases toward C16 and C4/C6 FA, respectively. Also, selectivity toward unsaturated C18:X FA as a group was modulated by changes in a(w) for three of the four lipase studied. Resin-fixed lipases from R. miehei and C. antarctica exhibited profound differences in activity and FA selectively in response to changes in a(w'), relative to free and Celite-bound forms. These findings suggest that FA selectivity for lipid modification is influenced by a(w) and immobilization, but that each lipase has a characteristic response to these factors in a manner that cannot be predicted.

Anion Exchange Resins↗
PubMed2001

Low-frequency collective chain dynamics in a model biomembrane.

Proton NMR was employed as a probe for the collective hydrocarbon chain dynamics in decylammonium chloride (C10H21NH3Cl), a model biomembrane undergoing an irreversible structural phase transition sequence. Our rotating frame spin-lattice relaxation measurements revealed a low-frequency critical collective chain dynamics in the kHz regime, which is associated with the interdigitated to noninterdigitated chain configurational phase transition.

Amines↗
PubMed2001

Synthesis and biological evaluation of clitocine analogues as adenosine kinase inhibitors.

Adenosine kinase (AK) is the primary enzyme responsible for adenosine metabolism. Inhibition of AK effectively increases extracellular adenosine concentrations and represents an alternative approach to enhance the beneficial actions of adenosine as compared to direct-acting receptor agonists. Clitocine (3), isolated from the mushroom Clitocybe inversa, has been found to be a weak inhibitor of AK. We have prepared a number of analogues of clitocine in order to improve its potency and demonstrated that 5'-deoxy-5'-amino-clitocine (7) improved AK inhibitory potency by 50-fold.

Adenosine Kinase↗
PubMed2001

Frequent epigenetic inactivation of RASSF1A in human bladder carcinoma.

Allelic deletion or transcriptional silencing of RASSF1, a putative tumor suppressor at 3p21.3, has been found in a considerable proportion of lung, breast, and ovarian cancers. In this study, we analyzed the expression and mutation status of three RASSF1 isoforms (-A, -B, and -C) in 55 primary bladder carcinomas and 10 bladder and prostate cancer cell lines. The RASSF1A transcript was not found in 80% (4 of 5) and 100% (4 of 4) of bladder and prostate cell lines, respectively. Compared with normal bladder tissues, loss or significant reduction of RASSF1A was identified in 62% (34 of 55) of primary bladder carcinomas and 10 (83%) of 12 matched sets showed tumor-specific alteration of RASSF1A expression. Moreover, loss or abnormal down-regulation of RASSF1A correlated with advanced tumor stage. RASSF1B was undetectable in 60% (3 of 5) of bladder cell lines and in 31% (17 of 55) of primary tumors, but none of these tumors showed altered expression exclusively in RASSF1B. RASSF1C transcript was detected in all cell lines and primary tumors we examined. Expression of RASSF1A and RASSF1B was reactivated in all nonexpressor cell lines by treatment with the demethylating agent 5-aza-2'-deoxycytidine. Bisulfite DNA sequencing analysis revealed that aberrant hypermethylation at the CpG island in the RASSF1A promoter is strongly associated with the loss of RASSF1A expression in cell lines and uncultured primary tumors. Methylation-specific PCR and BstUI digestion analyses also demonstrated that 97% (33 of 34) of RASSF1A-nonexpressing primary tumors are methylated. Although somatic mutations were not identified in RASSF1 transcripts expressed in unmethylated tumors, 24% (9 of 37) of methylated cell lines and primary tumors showed detectable reductions in genomic levels of RASSF1, suggesting that RASSF1A inactivation might be caused by both epigenetic and genetic mechanisms in a subset of bladder tumors. Together, our data suggest that RASSF1A inactivation may play a critical role in the malignant progression of human bladder carcinomas.

Adult↗
PubMed2001

Quantification of bacterial polysaccharides by the purpald assay: measurement of periodate-generated formaldehyde from glycol in the repeating unit.

We have adapted the purpald assay for measurement of bacterial polysaccharides (PS) containing substituted and/or unsubstituted glycol (SG or UG) in residues such as glycerol, ribitol, arabinitol, furanosyl galactose, and sialic acid. For the purpald assay of UG-containing PS, 50 microL of PS samples was consecutively reacted with 50 microL of 16 mM NaIO4 for 20 min, 50 microL of 136 mM purpald reagent in 2 N NaOH for 20 min, and 50 microL of 64 mM NaIO4 for 20 min in a 96-well tissue culture plate followed by a measurement of absorbance at 550 nm with a plate reader. For SG-containing PS, conversion of SG to UG with 25 micro;L of 0.3 N NaOH, 1 h at room temperature for de-O-acetylation followed by 25 microL of 0.6 M H2SO4, 1 h at 80 degrees C for acid hydrolysis of PS precedes the periodate treatment in the purpald assay. The concentration of the samples can be calculated from the sample absorbance and the reference standard curve constructed from the reference concentrations of the same PS (well-characterized) and their corresponding absorbance values assayed in the same plate. The purpald assay provides a tool in addition to the existing ones for the measurement of glycol-containing PS. Among the usefulness of this method are the determinations of the glycerol content in the phospho-glycerol-containing PS and the SG and UG contents and structural integrity in PS and conjugate vaccines.

Bacteria↗
PubMed2001

Role of cAMP-dependent protein kinase in the regulation of DNA repair.

Enhanced DNA repair is an important factor in drug resistance in cancer. Using cell-free extracts derived from the fission yeast, Schizosaccharomyces pombe, we demonstrate in an in vitro system DNA repair system that increased cAMP levels, which activates cAMP-dependent protein kinase (PKA), inhibits repair of ultraviolet (UV)-damaged DNA. Supplementing the cell-free system with the catalytic kinase subunit of PKA also inhibits DNA repair. In contrast, addition of the PKA inhibitor H-89 enhances repair activity. These results show that PKA regulates DNA repair synthesis, thus implicating the cAMP signaling pathway in DNA damage response and repair of UV-damaged DNA lesions.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2001

The mechanism of phenylephrine-mediated [Ca(2+)](i) oscillations underlying tonic contraction in the rabbit inferior vena cava.

1. We characterized the mechanisms in vascular smooth muscle cells (VSMCs) that produce asynchronous, wave-like Ca(2+) oscillations in response to phenylephrine (PE). Confocal imaging was used to observe [Ca(2+)](i) in individual VSMCs of intact inferior vena cava (IVC) from rabbits. 2. It was found that the Ca(2+) waves were initiated by Ca(2+) release from the sarcoplasmic reticulum (SR) via inositol 1,4,5-trisphosphate-sensitive SR Ca(2+) release channels (IP(3)R channels) and that refilling of the SR Ca(2+) store through the sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase (SERCA) was required for maintained generation of the repetitive Ca(2+) waves. 3. Blockade of L-type voltage-gated Ca(2+) channels (L-type VGCCs) with nifedipine reduced the frequency of PE-stimulated [Ca(2+)](i) oscillations, while additional blockade of receptor-operated channels/store-operated channels (ROCs/SOCs) with SKF96365 abolished the remaining oscillations. Parallel force measurements showed that nifedipine inhibited PE-induced tonic contraction by 27 % while SKF96365 abolished it. This indicates that stimulated Ca(2+) entry refills the SR to support the recurrent waves of SR Ca(2+) release and that both L-type VGCCs and ROCs/SOCs contribute to this process. 4. Application of the Na(+)-Ca(2+) exchanger (NCX) inhibitors 2',4'-dichlorobenzamil (forward- and reverse-mode inhibitor) and KB-R7943 (reverse-mode inhibitor) completely abolished the nifedipine-resistant component of [Ca(2+)](i) oscillations and markedly reduced PE-induced tone. 5. Thus, we conclude that each Ca(2+) wave depends on initial SR Ca(2+) release via IP(3)R channels followed by SR Ca(2+) refilling through SERCA. Na(+) entry through ROCs/SOCs facilitates Ca(2+) entry through the NCX operating in the reverse mode, which refills the SR and maintains PE-induced [Ca(2+)](i) oscillations. In addition some Ca(2+) entry through L-type VGCCs and ROCs/SOCs serves to modulate the frequency of the oscillations and the magnitude of force development.

Animals↗
PubMed2001

All-optical measurements of the bending rigidity of lipid-vesicle membranes across structural phase transitions.

By exploiting the nanometer sensitivity of the confocal response to the position of an in-focus reflecting surface, we measured the bending rigidity of lipid-bilayer vesicles with a noninvasive all-optical method. The vesicles were weakly deformed with femtonewton optical force, and the bending rigidity was measured continuously from the L(alpha) through the P(beta(')) to the L(beta(')) phases on the same specimen for the first time. The bending modulus is found to increase by an order of magnitude from the L(alpha) phase to the L(beta(')) phase, as a result of the increasing area-compressibility modulus and bilayer thickness. The dips of bending modulus give precisely the main-transition and pretransition temperatures, which supports the recently proposed chain-melting model of pretransition.

Elasticity↗
PubMed2001

Increase in the expression of human leukocyte antigen class I in human fibroblasts by soluble factors secreted from human cytomegalovirus-infected cells.

The human cytomegalovirus (HCMV) is known to downregulate the expression of the human leukocyte antigen (HLA) class I for escape from immune surveillance. In order to understand the HCMV immune evasion mechanism, expression of HLA class I on the surface of HCMV-infected cells was investigated. A decrease in the HLA class I expression was observed at higher MOI; whereas at a lower MOI a slight increase in the HLA class I expression was observed. When HCMV-infected and uninfected cells were separately prepared on coverslips and co-cultured, the increased HLA class I expression was observed in uninfected cells. Treatment of the uninfected cells with the culture supernatant from HCMV-infected cells resulted in an increase in the HLA class I expression. A biochemical analysis of the HCMV-infected cell culture supernatant revealed the presence of interferon (IFN) beta interleukin (IL)-1beta, and IL-6. The HLA class I-enhancing activity of the culture supernatant was mimicked by IFN beta, but not by IL1-beta or IL-6, and was partially reversed by pretreatment with an antibody to IFN beta. Therefore, it appears that the HCMV infection of human foreskin fibroblast cells induces interferon beta and other soluble factor(s) that are responsible for the up-regulation of the HLA class I expression.

Cells, Cultured↗