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Fulltext Anterior chamber implantation at University Hospital, Kuala Lumpur

Lim TK

Med J Malaysia, 1984 Sep;39(3):205-9.
PMID: 6544921

50 cases of anterior chamber intraocular lens implantation at the University Hospital, Kuala Lumpur were studied. 80% of the cases achieved visual acuity of 6/9 or better. The percentage would be higher if cases with pre-existing pathology are excluded and the period of follow-up is longer. Complications, mainly minor and non sight-threatening, are discussed.
Fulltext The use of ultrasound in ocular biometry

Kuan BB, Lim TK

Med J Malaysia, 1984 Dec;39(4):280-4.
PMID: 6544933

Ultrasound measurement of ocular dimension is the chosen method for assessing axial length when determining dioptric power for intraocular lens. From the current results of 30 cases studied, the mean axial length ranges from 22 to 23 mm. Despite the limitation of the accuracy of the ultrasonic measurements with the 7.5 mHz transducer, the power of intraocular lens can. be determined satisfactorily in accordance with the knowledge of keratometric reading. Hence, high refractive errors could be avoided post-operatively.
Fulltext Factors influencing pulse oximetry as compared to functional arterial saturation in multi-ethnic Singapore

Lee KH, Hui KP, Tan WC, Lim TK

Singapore Med J, 1993 Oct;34(5):385-7.
PMID: 8153680

Noninvasive oximetry provides continuous monitoring of arterial oxygen saturation and hence, early detection of hypoxia. This has proved to be a useful adjunct to patients' safety, and is considered indispensable in certain settings. However, errors may be present in the pulse oximeter estimation (SpO2) of arterial oxygen saturation (SaO2), which may be due to various parameters. We have studied a multi-ethnic population where the skin pigmentation is different, and also under different conditions comparing SpO2 with SaO2. Our results showed that SpO2 estimation of SaO2 amongst the three racial groups (Chinese, Malays, and Indians) varied significantly (ANOVA, p < 0.05). The over-estimation was more pronounced by hypoxic conditions and jaundice. Haemoglobin and systolic blood pressure did not affect the difference between SpO2 and SaO2.
Potential protein hydrolysates from the white and purple flower varieties of Orthosiphon aristatus leaves

Chua LS, Abdullah FI, Lim TK, Lin Q

Food Chem, 2024 Jan 30;432:137261.
PMID: 37651783 DOI: 10.1016/j.foodchem.2023.137261

This study was aimed to extract bioactive peptides from the white and purple flower varieties of Orthosiphon aristatus leaves. The herb is well known for its pharmacological importance, possibly attributed to its plant proteins. Phenol based extraction was used to extract plant proteins, and then hydrolysed by proteolytic enzymes such as trypsin (serine protease) and pepsin (aspartic protease). MS/MS analysis revealed that 145 and 125 proteins were detected from the white and purple flower varieties, respectively. Trypsin hydrolysates were showed to have a higher degree of hydrolysis (24-33%), resulting in higher antioxidant and antibacterial activities. The white flower of trypsin hydrolysates showed a higher radical scavenging activity which could be attributed to its higher content of stress proteins (19%). However, trypsin hydrolysates from the purple flower showed higher ferric reducing power and bacterial growth inhibition. The performance of hydrolysates was better than ampicillin in inhibiting Acinetobacter baumanni and Staphylococcus aureus.
Cytotoxic mechanisms of panduratin A on A375 melanoma cells: A quantitative and temporal proteomics analysis

Lai SL, Wong PF, Lim TK, Lin Q, Mustafa MR

Proteomics, 2015 May;15(9):1608-21.
PMID: 25594392 DOI: 10.1002/pmic.201400039

Melanoma is a lethal form of skin cancer with rising global incidence. However, limited treatment options are available for advanced melanoma and this is further compounded by the development of resistance toward existing drugs. Panduratin A (PA), a cyclohexanyl chalcone found in Boesenbergia rotunda, was investigated for its cytotoxic potentials against human malignant melanoma A375 cells. Our initial findings revealed that mitochondrion is the primary acting site of PA on A375 cancer cells and the cytotoxic mechanisms of PA were further investigated using a temporal quantitative proteomics approach by iTRAQ 2D-LC-MS/MS. Comprehensive proteomics analysis identified 296 proteins that were significantly deregulated in PA-treated A375 cells and revealed the involvement of mitochondrial oxidative phosphorylation, secretory and ER stress pathway, and apoptosis. We further confirmed that the PA-induced apoptosis was mediated by prolonged ER stress at least in part via the PERK/eIF2α/ATF4/CHOP pathway. Pretreatment with cycloheximide, an ER stress inhibitor rescued PA-induced cell death, which was accompanied by the suppression of ER-stress-related HSPA5 and CHOP proteins. The present study provides comprehensive mechanistic insights into the cytotoxic mechanisms of PA.
iTRAQ-based proteomic identification of proteins involved in anti-angiogenic effects of Panduratin A on HUVECs

Lai SL, Wong PF, Lim TK, Lin Q, Mustafa MR

Phytomedicine, 2015 Jan 15;22(1):203-12.
PMID: 25636890 DOI: 10.1016/j.phymed.2014.11.016

Panduratin A (PA), a cyclohexanyl chalcone from Boesenbergia rotunda (L.) Mansf. was shown to possess anti-angiogenic effects in our previous study. In the present study, the molecular targets and anti-angiogenic mechanisms of PA on human umbilical vein endothelial cells (HUVECs) were identified using an iTRAQ-based quantitative proteomics approach. A total of 263 proteins were found to be differentially regulated in response to treatment with PA. Ingenuity Pathway Analysis revealed that cellular growth and proliferation, protein synthesis, RNA post-transcriptional modification, cellular assembly and organization and cell-to-cell signaling and interaction were the most significantly deregulated molecular and cellular functions in PA-treated HUVECs. PA inhibited the expressions of ARPC2 and CTNND1 that are associated with the formation of actin cytoskeleton, focal adhesion and cellular protrusions. In addition, PA down-regulated CD63, GRB-2, ICAM-2 and STAB-1 that are implicated in adhesion, migration and tube formation of endothelial cells. The differential expressions of three targets, namely, ARPC2, CDK4, and GRB-2 were validated by western blot analyses. Furthermore, PA inhibited G1-S progression, and resulted in G0/G1 arrest in HUVECs. The blockage in cell cycle progression was accompanied with the suppression of mTOR signaling. Treatment of HUVECs with PA resulted in decreased phosphorylation of ribosomal S6 and 4EBP1 proteins, the two downstream effectors of mTOR signaling. We further showed that PA is able to inhibit mTOR signaling induced by VEGF, a potent inducer of angiogenesis. Taken together, by integrating quantitative proteomic approach, we identified protein targets in which PA mediates its anti-angiogenic effects. The present study thus provides mechanistic evidence to the previously reported multifaceted anti-angiogenic effects of PA. Our study further identified mTOR signaling as an important target of PA, and therefore highlights the potential of PA for therapeutic intervention against angiogenesis-related pathogenesis, particularly, metastatic malignancy.
Fulltext Entamoeba histolytica: Quantitative Proteomics Analysis Reveals Putative Virulence-Associated Differentially Abundant Membrane Proteins

Ng YL, Olivos-García A, Lim TK, Noordin R, Lin Q, Othman N

Am J Trop Med Hyg, 2018 12;99(6):1518-1529.
PMID: 30298805 DOI: 10.4269/ajtmh.18-0415

Entamoeba histolytica is a protozoan parasite that causes amebiasis and poses a significant health risk for populations in endemic areas. The molecular mechanisms involved in the pathogenesis and regulation of the parasite are not well characterized. We aimed to identify and quantify the differentially abundant membrane proteins by comparing the membrane proteins of virulent and avirulent variants of E. histolytica HM-1:IMSS, and to investigate the potential associations among the differentially abundant membrane proteins. We performed quantitative proteomics analysis using isobaric tags for relative and absolute quantitation labeling, in combination with two mass spectrometry instruments, that is, nano-liquid chromatography (nanoLC)-matrix-assisted laser desorption/ionization-mass spectrometry/mass spectrometry and nanoLC-electrospray ionization tandem mass spectrometry. Overall, 37 membrane proteins were found to be differentially abundant, whereby 19 and 18 membrane proteins of the virulent variant of E. histolytica increased and decreased in abundance, respectively. Proteins that were differentially abundant include Rho family GTPase, calreticulin, a 70-kDa heat shock protein, and hypothetical proteins. Analysis by Protein ANalysis THrough Evolutionary Relationships database revealed that the differentially abundant membrane proteins were mainly involved in catalytic activities (29.7%) and metabolic processes (32.4%). Differentially abundant membrane proteins that were found to be involved mainly in the catalytic activities and the metabolic processes were highlighted together with their putative roles in relation to the virulence. Further investigations should be performed to elucidate the roles of these proteins in E. histolytica pathogenesis.
Adjunctive pascolizumab in rifampicin-susceptible pulmonary tuberculosis: proof-of-concept, partially-randomised, double-blind, placebo-controlled, dose-escalation trial

Paton NI, Gurumurthy M, Lu Q, Leek F, Kwan P, Koh HWL, et al.

J Infect Dis, 2024 Mar 25.
PMID: 38527849 DOI: 10.1093/infdis/jiae104

BACKGROUND: Interleukin-4 (IL-4), increased in tuberculosis infection, may impair bacterial killing. Blocking IL-4 confers benefit in animal models. We evaluated safety and efficacy of pascolizumab (humanised anti-IL-4 monoclonal antibody) as adjunctive tuberculosis treatment.
METHODS: Participants with rifampicin-susceptible pulmonary tuberculosis received a single intravenous infusion of pascolizumab or placebo; and standard 6-month tuberculosis treatment. Pascolizumab dose increased in successive cohorts: [1] non-randomised 0.05 mg/kg (n = 4); [2] non-randomised 0.5 mg/kg (n = 4); [3] randomised 2.5 mg/kg (n = 9) or placebo (n = 3); [4] randomised 10 mg/kg (n = 9) or placebo (n = 3). Co-primary safety outcome was study-drug-related grade 4 or serious adverse event (G4/SAE); in all cohorts (1-4). Co-primary efficacy outcome was week-8 sputum culture time-to-positivity (TTP); in randomised cohorts (3-4) combined.
RESULTS: Pascolizumab levels exceeded IL-4 50% neutralising dose for 8 weeks in 78-100% of participants in cohorts 3-4. There were no study-drug-related G4/SAEs. Median week-8 TTP was 42 days in pascolizumab and placebo groups (p = 0.185). Rate of TTP increase was greater with pascolizumab (difference from placebo 0.011 [95% Bayesian credible interval 0.006 to 0.015] log10TTP/day.
CONCLUSIONS: There was no evidence to suggest blocking IL-4 was unsafe. Preliminary efficacy findings are consistent with animal models. This supports further investigation of adjunctive anti-IL-4 interventions for tuberculosis in larger phase 2 trials.