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Biomedical subjects

S J Lim

Publications and source records attributed to S J Lim.

31 records · Page 2Linked to original sources

Role of protein kinase C isozymes in activation of human immunodeficiency virus type 1 in chronically infected promonocytic cells: evidence against a role of PKC beta 1.

Protein kinase C (PKC) plays an important role in activation of human immunodeficiency virus type 1 (HIV-1). Because of a molecular and biochemical heterogeneity of PKC, we have studied the effects of PKC isozymes in HIV-1 activation in a latently infected promonocytic cell line, U1, using various PKC isozyme agonists. 12-Deoxyphorbol 13-phenylacetate (dPP), an agonist of both Ca(++)-dependent and Ca(++)-independent isozymes, and thymeleatoxin (TT), an agonist of Ca(++)-dependent PKC isozymes, induced HIV-1 production at 10 nM with increase in a concentration dependent manner, whereas 12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA), an PKC beta I isozyme agonist, did not induce viral production at 100 nM. We verified that dPPA induced translocation of PKC beta isozyme with the isozyme-specific monoclonal antibody using flow cytometry. This study demonstrates that activation of PKC isozymes leads to an induction of latent HIV-1 in U1 cells whereas PKC beta I isozyme may not be important.

Cell Survival↗

Liposome immunoassay (LIA) with antigen-coupled liposomes containing alkaline phosphatase.

Immunoliposomes were prepared and their immunoassay applications investigated. Liposomes were prepared from cholesterol and phospholipids including maleimidobenzoylphosphatidylethanolamine (MBPE) for conjunction with thiol-containing antigens. Alkaline phosphatase (APase) was entrapped in the liposome and BSA, the antigen, was modified by reaction with 3-(2-pyridyl-dithio)propionyl N-hydroxysuccinimide ester (SPDP) to introduce thiol groups for efficient coupling. BSA-coupled liposomes (immunoliposomes) were incubated with anti-BSA serum, complement, and then with APase substrate. The amount of coupled BSA was affected by the reaction time, the composition of the liposome and the BSA concentration in the reactant. The amount of enzyme released from immunoliposomes as a final result of the immunoreaction increased with increasing concentrations of complement and antibody. The liposome immunoassay offers a relatively rapid and simple testing procedure to quantitatively or qualitatively determine the presence or absence of antibodies, or antigenic materials for diagnostic purposes.

Alkaline Phosphatase↗

Water resource development and prevention of malaria.

The construction of dams across the mouths of major tidal rivers in the development of the Kranji Reservoir, Western Catchments Scheme and the Sungei Seletar Reservoir in Singapore created suitable environmental conditions for the propagation of anopheline brackish-water breeders. The employment of foreign contract workers from malarious areas for the projects further increased the potential risk of malaria transmission. However, constant vigilance and environmental management aimed at the permanent elimination of vector breeding habitats, supplemented with chemical control and anti-parasite measures successfully prevented the reintroduction of malaria in these highly receptive and vulnerable areas.

Animals↗

Epidemiological aspects of an outbreak of dengue fever/dengue haemorrhagic fever in Singapore.

A nation-wide outbreak of 260 cases of DF/DHF with 1 death occurred in Singapore from Apr-Sept 1986. The outbreak originated from 3 separate foci of transmission at the western, south-eastern and north-eastern parts of the island and then spread to other dengue receptive urban and suburban areas. The morbidity rate was highest in young male Chinese adults between 15 and 24 years of age. The outbreak was rapidly brought under control through destruction of adult Aedes mosquitoes, surveys and source reduction of larval breeding habitats, health education and to a certain extent law enforcement. The Aedes population was high in the main foci of transmission although the overall house index was only 1.1. Other factors which could have precipitated the outbreak included waning herd immunity of the human population and continuous introduction of dengue virus into the country.

Aedes↗

Recanalization of obstructed Tenckhoff peritoneal dialysis catheter: wire/stylet manipulation combined with endoluminal electrocauterization.

We report the results of fluoroscopically guided wire/stylet manipulation combined with endoluminal electrocauterization in seven patients with obstructed Tenckhoff peritoneal dialysis catheters. In preparation for clinical application, electrocauterization was performed using a stone basket to recanalize surgically removed Tenckhoff catheters obstructed with omental fat ingrowing through the side holes. All ingrowing omental fat was removed easily by electrocauterization with the rotating movement of a stone basket. The technique was then applied in vivo in seven cases with ingrowing omental fat and malpositioned catheter; six (86%) were successfully recanalized. Among those six cases with initial success, four maintained good catheter function with durable patency (mean 261.3 days). No significant complication was noted.

Adult↗

Altered pharmacokinetics and liver targetability of methotrexate by conjugation with lactosylated albumins.

To enhance the liver targetability, methotrexate (MTX) was conjugated with albumin previously substituted with varying content of lactose (L0, L5, and L24). The uptake of MTX by rat hepatocytes in vitro increased according to the increase in the lactose content on the albumin conjugates. The MTX level in the plasma and various organs was determined by counting the radioactivity of [3H]MTX and by HPLC assay, separately, to monitor the in vivo fate of MTX not only as total, regardless of forms of MTX, but also as free/intact MTX level. Conjugation of MTX with albumin alone provided the enhanced delivery of MTX to the liver, accompanied by decreased accumulation in the kidney, but by increased accumulation in other nontarget organs such lung, heart, and spleen. Lactosylation of albumin conjugates further enhanced the delivery of MTX to the liver in a lactose content-dependent manner, accompanied by decreased accumulation of MTX in the lung and heart as well as kidney. The total MTX level accumulated in the liver was 2.9-, 4.1-, and 11.0-fold higher at 1 h and 5.4-, 7.0-, and 16.5-fold higher at 4 h after injection of MTX-L0, L5, L24 albumin conjugates compared with MTX alone. MTX conjugates with lactosylated albumin provided low but prolonged level of free/intact MTX in the liver. Taken together, the pharmacokinetics and liver targetability of MTX could be favorably modulated by controlling the lactose content on the albumin conjugates. Lactosylated albumin conjugation might also provide prolonged and targeted delivery of other drugs for the treatment of liver diseases.

Animals↗

Prolonged blood circulation of methotrexate by modulation of liposomal composition.

Prolonged circulation by liposomal incorporation has been shown to enhance the therapeutic efficacy of drugs in many cases. The purpose of this study was to investigate whether the prolonged circulation of methotrexate (MTX) can be achieved by modulating the liposomal compositions. Various compositions of liposomes were prepared with 2:1 of phosphatidylcholine (PC) and cholesterol (CH) with or without distearoylphosphatidyl-ethanolamine-N-poly(ethyleneglycol) 2000 (DSPE-PEG). The MTX encapsulation efficiency depended on the type of PC used. It also appeared to increase by inclusion of DSPE-PEG. The size of liposomes decreased by the inclusion of DSPE-PEG. The inclusion of DSPE-PEG lowered the plasma-induced release of MTX from EggPC/CH and DPPC/CH liposomes, suggesting its enhancement effect on the liposomal stability. After intravenous injection to rats, the pharmacokinetics and biodistribution of MTX were significantly changed by liposomal incorporation and also by the composition of liposomes. The total body clearance of MTX incorporated in EggPC/CH, DPPC/CH, EggPC/CH/DSPE-PEG, and DPPC/CH/DSPE-PEG liposomes decreased 4.4-, 14.9-, 24.5-, and 53.1-fold, compared with that of free MTX. The ratio of MTX concentration in blood to liver and spleen after injection of DPPC/CH, EggPC/CH/DSPE-PEG, and DPPC/CH/DSPE-PEG liposomes was 5.4-, 8.5-, and 13.5-fold higher than that of EggPC/CH liposomes. Furthermore, the accumulation of MTX in the kidney, one of the organs in which MTX exhibits its toxicity, was significantly lowered by liposomal incorporation, especially by DSPE-PEG-containing liposomes. Taken together, DPPC/CH/DSPE-PEG liposomes most effectively prolonged the blood circulation, and reduced hepatosplenic and kidney uptake of MTX. DPPC/CH/DSPE-PEG liposomes may have potential as an efficient delivery system for MTX.

Animals↗

Nocardia keratitis after traumatic detachment of a laser in situ keratomileusis flap.

PURPOSE: Nocardia are gram-positive bacteria existing ubiquitously in the environment; they can cause keratitis. Nocardia asteroides keratitis occurred in the interface between the stromal bed and flap after traumatic detachment of the flap 4 months after an initially uncomplicated laser in situ keratomileusis (LASIK) procedure. METHODS: Nocardia asteroides keratitis was confirmed by culture. Therapy included topical and oral trimethoprim-sulfamethoxazole. RESULTS: Thirteen months after the trauma, the patient's spectacle-corrected visual acuity was 20/20 with a manifest refraction of -2.25 -1.00 x 30 degrees. CONCLUSIONS: The immediate steps of management consisting of surgically lifting the corneal flap, rapid microbial identification, and proper treatment with specific antibiotics resulted in the successful treatment of Nocardia asteroides keratitis in a traumatized eye after LASIK.

Adult↗

Effect of 0.2% brimonidine in preventing intraocular pressure elevation after Nd:YAG laser posterior capsulotomy.

BACKGROUND AND OBJECTIVE: To determine the prophylactic effect of 0.2% brimonidine in reducing the elevated intraocular pressure (IOP) in patients undergoing Nd:YAG laser posterior capsulotomy. PATIENTS AND METHODS: The 81 patients (81 eyes), who underwent Nd:YAG laser posterior capsulotomy, were allocated to two treatment groups. One drop of 0.2% brimonidine or vehicle was instilled 1 hour preoperatively and one drop immediately after capsulotomy. IOPs were measured preoperatively and 1, 2, 3, and 24 hours postoperatively. RESULTS: Intraocular pressure decreased from the baseline in the brimonidine group by the third postoperative hour (P<0.05), while the vehicle group exhibited an increase. Intraocular pressure elevations of 5 mm Hg or greater occurred in 7.3% (3/41) in the brimonidine group compared to 20.0% (8/40) in the vehicle group. IOP elevations of 10 mm Hg or greater occurred in 2.4% (1/41) in the brimonidine group compared to 7.5% (3/40) in the vehicle group. CONCLUSIONS: One drop of 0.2% brimonidine instilled 1 hour preoperatively and immediately after capsulotomy was found to be efficacious and safe in preventing IOP elevations that frequently follow Nd:YAG laser posterior capsulotomy.

Adrenergic alpha-Agonists↗