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Biomedical subjects

W S Lee

Publications and source records attributed to W S Lee.

At least 19 recordsLinked to original sources

Pulsatility of ascending aorta and restenosis after coronary angioplasty in patients >60 years of age with stable angina pectoris.

A recent study has demonstrated that the pulsatility of the ascending aorta is a strong predictive factor for restenosis after coronary angioplasty. However, whether the pulsatility of the ascending aorta is still a significant predictor for restenosis in elderly patients with a stiffer aorta is unknown. We investigated the relation between arterial pulsatility in the ascending aorta and restenosis after coronary angioplasty in patients aged > 60 years. Eighty-seven consecutive patients (80 men, aged 72.5 +/- 5.1 years) with stable angina were included. Before angioplasty, the arterial systolic, diastolic, and mean pressure waveforms of the ascending aorta were measured. We used fractional pulse pressure (PPf, the ratio of pulse pressure to mean pressure) and pulsatility index (PI, the ratio of pulse pressure to diastolic pressure) to estimate the pulsatility of the ascending aorta. Angiographic restenosis occurred in 39 patients. Pulse pressure, PPf, and PI were significantly higher in patients with restenosis after coronary angioplasty (restenosis vs without restenosis: pulse pressure, 77.6 +/- 12.2 vs 66.1 +/- 15.4 mm Hg [p < 0.001]; PPf, 0.80 +/- 0.09 vs 0.69 +/- 0.11 [p < 0.001]; PI, 1.19 +/- 0.20 vs 0.98 +/- 0.21 [p < 0.001]). After multivariate stepwise adjustment of risk factors of restenosis and using receiver-operating characteristic analysis, the odds ratio (OR) of restenosis was: pulse pressure > 66 mm Hg, OR 5.88 (95% confidence interval [CI] 2.17 to 15.93); PPf > 0.72, OR 13.71 (95% CI 4.81 to 39.05); PI > 1.06, OR 13.56 (95% CI 4.67 to 39.38). Moreover, among patients aged > 70 years (n = 60), the predictive values of PPf and PI were even higher than those in patients aged < or = 70 years (n = 27). Thus, in elderly patients with stable angina, the pulsatility of the ascending aorta is a powerful predictor of restenosis after coronary angioplasty.

Aged↗

Liquid crystalline polysiloxane polymer as stationary phase in gas chromatography capillary column for the separation of dioxin/furan compounds.

A side-chain liquid crystalline polysiloxane polymer (PS3DBDE1) with high purity and high isotropic transition temperature served as a stationary phase in an attempt to chromatographize the dioxin/furan compounds. The polymer was coated on the inner surface of a 0.25 mm I.D. capillary column by using the static coating method, forming a film with a thickness of df approximately 0.25 microm. A commercial standard solution (US EPA 1613 standard solution 1613CS4) containing polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) was used to test the chromatographic behavior of the laboratory-made capillary column. Two commercial capillary columns HP-5MS (Hewlett-Packard) and RTX-5MS (RTX) were chosen to compare their chromatographic behavior. The results show that by the use of PS3DBDE1 the isomeric pair compounds 1,2,3,4-TeCDD vs. 2,3,7,8-TeCDD and 1,2,3,4,7,8-HxCDD vs. 1,2,3,6,7,8-HxCDD and the same substituted-chlorine number compounds 1,2,3,4,6,7,8-HpCDF vs. 1,2.3,4,6,7,8-HpCDD and 1,2,3,4,6,7,8,9-OCDD vs. 1,2,3,4,6,7,8,9-OCDF had higher resolution than HP-5MS and RTX-5MS as suggested by the column makers.

Chromatography, Gas↗

Asymmetric inter- and intramolecular cyclopropanation of alkenes catalyzed by chiral ruthenium porphyrins. Synthesis and crystal structure of a chiral metalloporphyrin carbene complex.

Extensive investigations of asymmetric intermolecular cyclopropanation of terminal alkenes with diazoacetates catalyzed by ruthenium porphyrin [Ru(P*)(CO)(EtOH)] (1, H2P = 5,10,15,20-tetrakis[(1S,4R,5R,8S)-1,2,3,4,5,6,7,8-octahydro-1,4:5,8-dimethanoanthracene-9-yl]porphyrin) and the application of catalyst 1 to asymmetric intramolecular cyclopropanation of allylic or homoallylic diazoacetates are described. The intermolecular cyclopropanation of styrene and its derivatives with ethyl diazoacetate afforded the corresponding cyclopropyl esters in up to 98% ee with high trans/cis ratios of up to 36 and extremely high catalyst turnovers of up to 1.1 x 10(4). Examination of the effects of temperature, diazoacetate, solvent, and substituent in the intermolecular cyclopropanation reveals that (i) both enantioselectivity and trans selectivity increase with decreasing temperature, (ii) sterically encumbered diazoacetates N2CHCO2R, such as R = Bu(t), and donor solvents, such as diethyl ether and tetrahydrofuran, are beneficial to the trans selectivity, and (iii) electron-donating para substituents on styrene accelerate the cyclopropanations, with the log(k(X)/k(H)) vs sigma(+) plot for para-substituted styrenes p-X-C6H4CH=CH2 (X = MeO, Me, Cl, CF3) exhibiting good linearity with a small negative rho(+) value of -0.44 +/- 0.09. In the case of intramolecular cyclopropanation, complex 1 promoted the decomposition of a series of allylic diazoacetates to form the cyclopropyl lactones in up to 85% ee, contributing the first efficient metalloporphyrin catalyst for an asymmetric intramolecular cyclopropanation. Both the inter- and intramolecular cyclopropanations were proposed to proceed via a reactive chiral ruthenium carbene intermediate. The enantioselectivities in these processes were rationalized on the basis of the X-ray crystal structures of closely related stable chiral carbene complexes [Ru(P*)(CPh2)] (2) and [Ru(P*)(C(Ph)CO2CH2CH=CH2)] (3) obtained from reactions of complex 1 with N2CPh2 and N2C(Ph)CO2CH2CH=CH2, respectively.

Journal Article↗

Molecular mechanisms of apoptosis induced by magnolol in colon and liver cancer cells.

Magnolol has been reported to have anticancer activity. In this study we found that treatment with 100 microm magnolol induced apoptosis in cultured human hepatoma (Hep G2) and colon cancer (COLO 205) cell lines but not in human untransformed gingival fibroblasts and human umbilical vein endothelial cells. Our investigation of apoptosis in Hep G2 cells showed a sequence of associated intracellular events that included (a) increased cytosolic free Ca(2+); (b) increased translocation of cytochrome c (Cyto c) from mitochondria to cytosol; (c) activation of caspase 3, caspase 8, and caspase 9; and (d) downregulation of bcl-2 protein. Pretreatment of the cells with the phospholipase C inhibitor 1-[6-[[(17 beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1 H-pyrrole-2,5-dione (U73122) or the intracellular chelator of Ca(2+) 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA/AM) inhibited the subsequent magnolol augmentation of [Ca(2+)](i) and also the activation of caspase-8 and caspase-9, so that the occurrence of apoptosis in those cells was greatly reduced. Pretreatment of the cells with ZB4 (which disrupts the Fas response mechanism) also decreased the subsequent magnolol-induced caspase-8 activation and reduced the occurrence of apoptosis. We interpreted these findings to indicate that the above-listed sequence of intracellular events led to the apoptosis seen in Hep G2 cells and that [Ca(2+)](i), Cyto c, and Fas function as intracellular signals to coordinate those events.

Antineoplastic Agents, Phytogenic↗

Induction of cyclooxygenase-2 protein by lipoteichoic acid from Staphylococcus aureus in human pulmonary epithelial cells: involvement of a nuclear factor-kappa B-dependent pathway.

1. This study investigated the role of protein kinase C (PKC) and transcription factor nuclear factor-kappaB (NF-kappaB) in cyclooxygenase-2 (COX-2) expression caused by lipoteichoic acid (LTA), a cell wall component of the gram-positive bacterium Staphylococcus aureus, in human pulmonary epithelial cell line (A549). 2. LTA caused dose- and time-dependent increases in COX-2 expression and COX activity, and a dose-dependent increase in PGE(2) release in A549 cells. The LTA-induced increases in COX-2 expression and COX activity were markedly inhibited by dexamethasone, actinomycin D or cyclohexamide, but not by polymyxin B, which binds and inactivates endotoxin. 3. The phosphatidylcholine-phospholipase C (PC-PLC) inhibitor (D-609) and the phosphatidate phosphohydrolase inhibitor (propranolol) reduced the LTA-induced increases in COX-2 expression and COX activity, while phosphatidylinositol-phospholipase C inhibitor (U-73122) had no effect. The PKC inhibitors (Go 6976, Ro 31-8220 and GF 109203X) and NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), also attenuated the LTA-induced increases in COX-2 expression and COX activity. 4. Treatment of A549 cells with LTA caused an increase in PKC activity in the plasma membrane; this stimulatory effect was inhibited by D-609, propranolol, or Go 6976, but not by U-73122. 5. Exposure of A549 cells to LTA caused a translocation of p65 NF-kappaB from the cytosol to the nucleus and a degradation of IkappaB-alpha in the cytosol. Treatment of A549 cells with LTA caused NF-kappaB activation by detecting the formation of NF-kappaB-specific DNA-protein complex in the nucleus; this effect was inhibited by dexamethasone, D-609, propranolol, Go 6976, Ro 31-8220, or PDTC. 6. These results suggest that LTA might activate PC-PLC and phosphatidylcholine-phospholipase D to induce PKC activation, which in turn initiates NF-kappaB activation, and finally induces COX-2 expression and PGE(2) release in human pulmonary epithelial cell line.

Cyclooxygenase 2↗

A bone replaceable artificial bone substitute: osteoinduction by combining with bone inducing agent.

Bone inducing agent (BIA) isolated from Saos-2 human osteosarcoma cells was added to an artificial bone substitute composed of 980 degrees C-heated carbonate apatite (CAp) and Type I atelocollagen (AtCol) extracted from bovine tail skins (88/12 in wt/wt %), and a CAp-AtCol-BIA substitute was prepared as an osteoinductive bone substitute. Rat calvaria osteoblasts treated by the isolated BIA demonstrated significantly increased alkaline phosphatase (ALP) activity after 3 days (p < 0.05). In vitro cell attachment and proliferation and ALP activity were investigated for the bone substitute combined with BIA. Osteoblasts cultured onto the surface of the CAp-AtCol-BIA substitute demonstrated remarkable morphological changes such as radial spreading, flattening, and projecting filopodia after 5 days. In comparison with the substitute without BIA, osteoblasts grown in the BIA-combined CAp-AtCol substitute expressed significantly increased proliferation and ALP activity, respectively (p < 0.05). Both the substitutes combined with and without BIA were implanted into artificial defects created in rabbit radii. After 4 weeks, the CAp-AtCol-BIA substitute implanted lesion was completely replaced by regenerated host bone in radiological observation whereas the substitute without BIA was partially resorbed. No histologic abnormalities appeared in the substitute either with or without BIA.

Alkaline Phosphatase↗

Effect of bone morphogenetic protein-7 on folliculogenesis and ovulation in the rat.

We have previously established the presence of a functional bone morphogenetic protein (BMP) system in the ovary by demonstrating the expression of BMP ligands and receptors as well as novel cellular functions. Specifically, BMP-4 and BMP-7 are expressed in theca cells, and their receptors by granulosa cells. These BMPs enhanced and attenuated the stimulatory action of FSH on estradiol and progesterone production, respectively. To investigate the underlying mechanism of the differential regulation, we analyzed mRNA levels for key regulators in the steroid biosynthetic pathways by RNase protection assay. BMP-7 enhanced P450 aromatase (P450(arom)) but suppressed steroidogenic acute regulatory protein (StAR) mRNAs induced by FSH, whereas mRNAs encoding further-downstream steroidogenic enzymes, including P450 side-chain cleavage enzyme and 3beta-hydroxysteroid dehydrogenase, were not significantly altered. These findings suggest that BMP-7 stimulation and inhibition of P450(arom) and StAR mRNA expression, respectively, may play a role in the mechanisms underlying the differential regulation of estradiol and progesterone production. To establish the physiological relevance of BMP functions, we investigated the in vivo effects of injections of recombinant BMP-7 into the ovarian bursa of rats. Ovaries treated with BMP-7 had decreased numbers of primordial follicles, yet had increased numbers of primary, preantral, and antral follicles, suggesting that BMP-7 may act to facilitate the transition of follicles from the primordial stage to the pool of primary, preantral, and antral follicles. In this regard, we have also found that BMP-7 caused an increase in DNA synthesis and proliferation of granulosa cells from small antral follicles in vitro. In contrast to the stimulatory activity, BMP-7 exhibited pronounced inhibitory effects on ovulation rate and serum progesterone levels. These findings establish important new biological activities of BMP-7 in the context of ovarian physiology, including folliculogenesis and ovulation.

Animals↗

Marie Unna hypotrichosis in an Asian family.

We report on two patients from one family with Marie Unna hypotrichosis who showed a diffuse hair defect which typically occurs as an isolated phenomenon. The ultrastructural hair findings consisted of longitudinal grooving of the hair shafts and a flattening in cross-section. Characteristically, scalp hair had been lost from the scalp margins and a high frontal and nuchal hairline had been present at birth. Eyelashes were absent, and eyebrows, axillary, and pubic hair were very sparse. Other affected cases have been reported in Caucasian families; however, this is the first case in the English medical literature of a family from Asia affected by Marie Unna hypotrichosis.

Adult↗

The effects of famciclovir and epidural block in the treatment of herpes zoster.

In our previous study, we concluded that an epidural blockade combined with intravenous acyclovir is very effective in treating the acute pain in herpes zoster and postherpetic neuralgia. We evaluated the efficacy of oral famciclovir and epidural blockade on the pain of herpes zoster, compared to acyclovir administered intravenously and epidural blockade. For this purpose, we examined a new group treated with famciclovir and epidural blockade to compare with the group treated with acyclovir and epidural blockade in our previously study. The changes in the intensity of pain, the number of days required for relief of pain, and the total duration of pain were checked. We compared the days required for relief of pain (DRP) and the total duration of pain (TDP) of this group with those of the previous studied group treated with acyclovir and epidural blockade. DRP was significantly less, but TDP was similar. DRP and TDP were significantly lower, if the patients were treated within 7 days of symptom onset. The patients had a shorter DRP regardless of pain type than the previously studied group treated with acycolvir and epidural blockade. For the severe and moderate pain grades, there was a shorter DRP from 100 to 10. TDP was not significantly different for the groups regardless of pain type or grade. We believe that famciclovir and epidural blockade are very effective in treating the pain of herpes zoster, with a view to shortening the period of acute pain, providing similar effects on the prevention of postherpetic neuralgia, and being convenient to administer, compared to intravenous acyclovir and epidural blockade in our previous study.

2-Aminopurine↗

Bile bilirubin pigment analysis in disorders of bilirubin metabolism in early infancy.

BACKGROUND: Early and accurate diagnosis of Crigler-Najjar syndrome, which causes prolonged unconjugated hyperbilirubinaemia in infancy, is important, as orthotopic liver transplantation is the definitive treatment. AIM: To determine whether bilirubin pigment analysis of bile in infants with prolonged unconjugated hyperbilirubinaemia provides useful diagnostic information in the first 3 months of life. METHODS: Retrospective review of patients with prolonged unconjugated hyperbilirubinaemia referred to the liver unit, Birmingham Children's Hospital, for the diagnosis of Crigler-Najjar syndrome. Bile bilirubin pigment composition was determined by high performance liquid chromatography. Initial diagnoses were made based on the result of bile bilirubin pigment composition. Final diagnoses were made after reviewing the clinical course, response to phenobarbitone, repeat bile bilirubin pigment composition analysis, and genetic studies. RESULTS: Between 1992 and 1999, nine infants aged less than 3 months of age with prolonged hyperbilirubinaemia underwent bile bilirubin pigment analyses. Based on these, two children were diagnosed with Crigler-Najjar syndrome (CNS) type 1, six with CNS type 2, and one with Gilbert's syndrome. Five children whose initial diagnosis was CNS type 2 had resolution of jaundice and normalisation of serum bilirubin after discontinuing phenobarbitone, and these cases were thought to be normal or to have Gilbert's syndrome. One of the initial cases of CNS type 1 responded to phenobarbitone with an 80% reduction in serum bilirubin consistent with CNS type 2. In all, the diagnoses of six cases needed to be reviewed. CONCLUSIONS: Early bile pigment analysis, performed during the first 3 months of life, often shows high levels of unconjugated bilirubin or bilirubin monoconjugates, leading to the incorrect diagnosis of both type 1 and type 2 Crigler-Najjar syndrome.

Bile Pigments↗

Restoration of vasodilation and CBF autoregulation by genistein in rat pial artery after brain injury.

This study determined whether, after fluid percussion injury (FPI), tyrosine kinase activation is coupled to inhibition of K(+) channels and alteration in cerebral blood flow (CBF) autoregulation in the rat pial artery. Injury of moderate severity (2--2.5 atm) was produced by FPI in anesthetized rats equipped with a closed cranial window. The suppressed vasodilation of the pial arterioles to calcitonin gene-related peptide (CGRP) and levcromakalim (LMK) and altered lower limit of CBF autoregulation after FPI were restored by genistein but not by daidzein, an inactive analog. Vasodilation to S-nitroso-N-acetyl penicillamine (0.1--10 micromol/l) was, however, little influenced after FPI. The restored vasodilation was decreased by sodium orthovanadate, suggesting the reciprocal action of tyrosine phosphorylation and dephosphorylation. After FPI, CGRP-induced vasodilation restored by genistein (10 micromol/l) was strongly antagonized by iberiotoxin but not by glibenclamide, whereas LMK-induced vasodilation was, in contrast, inhibited by glibenclamide but not by iberiotoxin. Taken together, we suggest that, after FPI, activation of tyrosine kinase links the inhibition of K(+) channels to impaired autoregulatory vasodilation in response to acute hypotension and alteration in CBF autoregulation in the rat pial artery.

Animals↗

Clinical significance of microvessel density in multiple myeloma patients.

To investigate the role of angiogenesis in multiple myeloma (MM), bone marrow biopsy from 75 adults with newly diagnosed, untreated MM were evaluated. Microvessels were scored in at least 3 areas ( x 200 fields) of the highest microvessel density in representative sections of each bone marrow specimen using immunohistochemistry for CD34. Prognostic variables were also evaluated for the overall survival. Microvessel counts were significantly higher in patients with MM (n=69.42+/-9.67), compared with control (n=26.81+/-2.85). Microvessel density had a weak correlation with percentage of bone marrow plasma cells. By univariate analysis, age, beta2-microglobulin, serum albumin, serum creatinine, serum calcium, hemoglobin, platelet count, and bone marrow plasma cell percentage were correlated with survival. By multivariate analysis, age, serum albumin, serum creatinine, hemoglobin, platelet count and bone marrow plasma cell percentage were correlated with overall survival, whereas microvessel density was not. In summary, microvessel density in bone marrow of MM is significantly increased compared to control, but was not correlated with overall survival. Further studies regarding angiogeneic molecules are needed to determine the functional role of angiogenesis in MM.

Adult↗

Retrospective study of Aeromonas infection in a Malaysian urban area: a 10-year experience.

AIMS: To describe the patterns of isolation of Aeromonas spp. and the resulting spectrum of infection, intestinal and extra-intestinal,from infants and children in an urban area in a hot and humid country from SoutheastAsia. MATERIALS AND METHODS: Retrospective review of all bacterial culture records from children below 16 years of age, from the Department of Medical Microbiology, University of Malaya Medical Centre, Kuala Lumpur, from January 1988 to December 1997. Review of all stool samples and rectal swabs obtained from children during the same period were carried out to ascertain the isolation rate of Aeromonas sp. from stools and rectal swabs. The case records of those with a positive Aeromonas culture were retrieved and reviewed. RESULTS: During the study period, 84 culture samples were positive of Aeromonas spp. (stools 48, rectal swabs 36). During the same period, 1,352 stool samples were positive for at least one enteropathogen. Aeromonas spp. constituted 0.62% of all stool samples. Of the 61 cases reviewed,four patterns of colonization were observed: (a) 17 cases of mostly asymptomatic nursery newborns with a positive rectal swab; (b) 9 children with no diarrhoea; (c) 23 cases, of who seven were immunocompromised, had acute, brief watery diarrhoea without severe dehydration or disturbances of serum electrolytes. No chronic diarrhoea or bacteraemia was noted. (d) 12 cases had a mixed infection with a second enteropathogen isolated from stool samples. Three had chronic diarrhoea No extra-intestinal infection attributed to Aeromonas spp. was identified in this study. CONCLUSION: Aeromonas was a rare cause of gastroenteritis in urban Malaysian children. It was isolated almost exclusively from gastro-intestinal tract, caused mostly by mild gastroenteritis with no serious complications. Asymptomatic stool carriage among newborns admitted to special care nursery and older children with no diarrhoea were observed.

Academic Medical Centers↗

Seroprevalence of anti-HCV in an urban child population: a preliminary study from Kuala Lumpur.

A pilot study to determine the seroprevalence of anti-HCV among children from Kuala Lumpur, Malaysia, was conducted using microparticle enzyme immunoassay. Serum samples were obtained randomly from children, aged between one to 16 years of age, admitted to the paediatric unit of University of Malaya Medical Centre, Kuala Lumpur for various medical reasons. Of the 179 samples assayed, only one was positive, giving the prevalence rate of 0.6%. It is reasonable to conclude that the seroprevalence of anti-HCV among children from Kuala Lumpur is low, less than 1%.

Adolescent↗

Ketoconazole induces G0/G1 arrest in human colorectal and hepatocellular carcinoma cell lines.

Ketoconazole is an oral-antifungal agent that has been used worldwide in the treatment of some hormone-dependent human cancer. In this study, we demonstrated that ketoconazole (20 microM) induced various types of human cancer cell growth arrest in the G0/G1 phase. Our results revealed that ketoconazole-induced growth arrest was more profound in COLO 205 and Hep G2 (with wild-type p53) than in HT 29 (p53 His(273) mutant) and Hep 3B (with deleted p53) cells. The protein levels of p53, p21/Cip1, and p27/Kip1 were significantly elevated by ketoconazole (10 microM) treatment in COLO 205 but not in HT 29 cells. The ketoconazole-induced G0/G1 phase arrest in COLO 205 cells was attenuated by p53-specific antisense oligodeoxynucleotides (20 microM) treatment. These results suggested that the p53-associated signaling pathway is involved in the regulation of ketoconazole-induced cancer cell growth arrest. By Western blot analysis, we demonstrated that cyclin D3 and CDK4 protein but not other G0/G1 phase regulatory protein levels were decreased by ketoconazole-treatment in both COLO 205 and HT 29 cells. Our study provides the basis of molecular mechanisms for ketoconazole in growth inhibition of human cancer cells and such results may have significant applications for cancer chemotherapy.

Animals↗

Airway obstruction caused by a congenital epiglottic cyst.

Congenital epiglottic cyst is a rare affliction with potential for airway obstruction. A newborn boy was referred to our department for evaluation of respiratory distress and inspiratory stridor 7 h after birth. Through a transnasal fiberoptic laryngoscopy examination, a diagnosis of an obstructive upper laryngeal cyst was made. Immediate endoscopic surgery was performed 20 h after birth to completely remove the lesion. Two days after surgery, the patient resumed normal breathing pattern and showed no further episodes of stridor or airway obstruction.

Airway Obstruction↗