Displaying publications 1 - 20 of 39 in total

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  1. Chan SK, Asirvatham CV
    Med J Malaysia, 2001 Mar;56(1):71-6.
    PMID: 11503300
    A study on infant feeding practices was conducted during the implementation of the Baby Friendly Hospital Initiative (BFHI) in a district hospital. The aim was to identify which population subgroups had lower breastfeeding rates at 4 months and the effect of attendance of antenatal breastfeeding education on breastfeeding practices. All infants delivered in May 1996 were followed-up. 204 respondents were analyzed. This study demonstrated a higher exclusive and any breastfeeding rates at 4 months than some other studies. (48% and 76% respectively). It was found that the Malays were more likely to be breastfeeding exclusively at 4 months (72%) than the Indians (32%) and the Chinese (4%). (P < 0.01). There were more non-working mothers breastfeeding exclusively at 4 months than working mothers. (60% versus 26%) P < 0.01. Antenatal breastfeeding education in the form that was given appeared to improve breastfeeding rates at 4 months. Future efforts to promote breastfeeding should target the Chinese mothers and the working mothers.
  2. Chan SK, Lim TS
    Appl Microbiol Biotechnol, 2019 Apr;103(7):2973-2984.
    PMID: 30805670 DOI: 10.1007/s00253-019-09669-3
    Microbial transglutaminase (mTGase) is commonly known in the food industry as meat glue due to its incredible ability to "glue" meat proteins together. Aside from being widely exploited in the meat processing industries, mTGase is also widely applied in other food and textile industries by catalysing the formation of isopeptide bonds between peptides or protein substrates. The advancement of technology has opened up new avenues for mTGase in the field of biomedical engineering. Efforts have been made to study the structural properties of mTGase in order to gain an in-depth understanding of the structure-function relationship. This review highlights the developments in mTGase engineering together with its role in biomedical applications including biomaterial fabrication for tissue engineering and biotherapeutics.
  3. Lim TS, Chan SK
    Curr Pharm Des, 2016;22(43):6480-6489.
    PMID: 27669969 DOI: 10.2174/1381612822666160923111924
    BACKGROUND: Antibody phage display is highly dependent on the availability of antibody libraries. There are several forms of libraries depending mainly on the origin of the source materials. There are three major classes of libraries, mainly the naïve, immune and synthetic libraries.

    METHODS: Immune antibody libraries are designed to isolate specific and high affinity antibodies against disease antigens. The pre-exposure of the host to an infection results in the production of a skewed population of antibodies against the particular infection.

    RESULTS: This characteristic takes advantage of the in vivo editing machinery to generate bias and specific immune repertoire. The skewed but diverse repertoire of immune libraries has been adapted successfully in the generation of antibodies against a wide range of diseases.

    CONCLUSION: We envisage immune antibody libraries to play a greater role in the discovery of antibodies for diseases in the near future.

  4. Chan SK, Lim TS
    Adv Exp Med Biol, 2017;1053:61-78.
    PMID: 29549635 DOI: 10.1007/978-3-319-72077-7_4
    The incident of two children in Europe who died of diphtheria due to a shortage of anti-toxin drugs has highlighted the need for alternative anti-toxins. Historically, antiserum produced from immunised horses have been used to treat diphtheria. Despite the potential of antiserum, the economical and medial concerns associated with the use of animal antiserum has led to its slow market demise. Over the years, new and emerging infectious diseases have grown to be a major global health threat. The emergence of drug-resistant superbugs has also pushed the boundaries of available therapeutics to deal with new infectious diseases. Antibodies have emerged as a possible alternative to combat the continuous onslaught of various infectious agents. The isolation of antibodies against pathogens of infectious diseases isolated from immune libraries utilising phage display has yielded promising results in terms of affinities and neutralizing activities. This chapter focuses on the concept of immune antibody libraries and highlights the application of immune antibody libraries to generate antibodies for various infectious diseases.
  5. Das Gupta M, Chan SK, Monteiro A
    PLoS One, 2015;10(7):e0132882.
    PMID: 26173066 DOI: 10.1371/journal.pone.0132882
    Commonly used visible markers for transgenesis use fluorescent proteins expressed at the surface of the body, such as in eyes. One commonly used marker is the 3xP3-EGFP cassette containing synthetic binding sites for the eyeless/Pax6 conserved transcription factor. This marker cassette leads to fluorescent eyes in a variety of animals tested so far. Here we show that upon reaching adulthood, transgenic Bicyclus anynana butterflies containing this marker cassette exponentially loose fluorescence in their eyes. After 12 days, transgenic individuals are no longer distinguishable from wild type individuals. The decreased eye fluorescence is likely due to significantly decreased or halted eyeless/Pax6 expression observed in wild type animals upon adult emergence. Implications from these findings include care in screening transgenic animals before these reach adulthood, or shortly thereafter, and in using adult animals of the same age for quantitative screening of likely homozygote and heterozygote individuals.
  6. Kho SS, Chan SK, Tie ST
    Respir Med, 2024;234:107805.
    PMID: 39265839 DOI: 10.1016/j.rmed.2024.107805
    BACKGROUND: Tuberculosis frequently poses diagnostic challenge when it presents as a peripheral pulmonary lesion (TB-PPL). The growing use of radial endobronchial ultrasound (rEBUS) for PPL biopsy highlights the need to identify predictive factors for TB-PPL, which is crucial for procedure safety.

    METHODS: A six-year retrospective review at our institution on adult patients with TB and malignant-PPL diagnosed from rEBUS procedure from October 1, 2016, to December 31, 2022. Clinical, radiological, procedural, histological and microbiological data were extracted and analysed.

    RESULTS: 387 PPLs were included in our cohort, 32 % were TB-PPL and 68 % were malignant-PPL. The median age was 63 (IQR 55-70) years, with the TB-PPL group significantly younger. The median size of the target lesion was 2.90 (IQR 2.26-4.00) cm. The overall rEBUS diagnostic yield was 85.3 %, with a 1.3 % pneumothorax risk. Multivariate analysis identified independent predictors for TB-PPL, including age <60 years (adj OR 2.635), target lesion size <2 cm (adj OR 2.385), upper lobe location (adj OR 2.020), presence of a cavity on pre-procedural CT (adj OR 4.186), and presence of rEBUS bronchogram (adj OR 2.722). These variables achieved an area under the curve of 0.729 (95 % CI 0.673-0.795) with a diagnostic accuracy of 75.49 % (95 % CI 70.68-79.88).

    CONCLUSIONS: Despite non-specific radiological findings in TB-PPL, our study identifies younger age, target lesion size less than 2 cm, upper lobe location, the presence of cavitation, and rEBUS bronchogram were independent clinical predictors for TB-PPL. This prediction model potentially helps mitigate the risk of accidental TB exposure during bronchoscopic procedures. A future prospective cohort study to validate these findings is essential to allow proper triaging of patient planning for rEBUS procedure.

  7. Soong JX, Chan SK, Lim TS, Choong YS
    J Comput Aided Mol Des, 2019 03;33(3):375-385.
    PMID: 30689080 DOI: 10.1007/s10822-019-00186-z
    Mycobacterium tuberculosis (Mtb) 16.3 kDa heat shock protein 16.3 (HSP16.3) is a latency-associated antigen that can be targeted for latent tuberculosis (TB) diagnostic and therapeutic development. We have previously developed human VH domain antibodies (dAbs; clone E3 and F1) specific against HSP16.3. In this work, we applied computational methods to optimise and design the antibodies in order to improve the binding affinity with HSP16.3. The VH domain antibodies were first docked to the dimer form of HSP16.3 and further sampled using molecular dynamics simulation. The calculated binding free energy of the HSP16.3-dAb complexes showed non-polar interactions were responsible for the antigen-antibody association. Per-residue free energy decomposition and computational alanine scanning have identified one hotspot residue for E3 (Y391) and 4 hotspot residues for F1 (M394, Y396, R397 and M398). These hotspot residues were then mutated and evaluated by binding free energy calculations. Phage ELISA assay was carried out on the potential mutants (E3Y391W, F1M394E, F1R397N and F1M398Y). The experimental assay showed improved binding affinities of E3Y391W and F1M394E against HSP16.3 compared with the wild type E3 and F1. This case study has thus showed in silico methods are able to assist in optimisation or improvement of antibody-antigen binding.
  8. Kho SS, Chan SK, Yong MC, Tie ST
    Med J Malaysia, 2020 05;75(3):254-259.
    PMID: 32467541
    INTRODUCTION: Pleural effusion is frequently encountered in respiratory medicine. However, despite thorough assessment including closed pleural biopsy, the cause of around 20% of pleural effusions remains undetermined. Medical thoracoscopy (MT) is the investigation of choice in these circumstances especially if malignancy is suspected. The aim of this study is to evaluate the diagnostic yield of MT in exudative pleural effusions in a single center from East Malaysia.

    METHODS: Retrospective chart review of all adult patients who underwent MT for undiagnosed exudative pleural effusion in a 24-month duration.

    RESULTS: Our cohort comprised of 209 patients with a median age of 61 years old (IQR 48.5-69.5). There were 92 (44%) patients with malignant pleural effusion (MPE) and 117 (56%) benign effusions; which included 85 tuberculous pleural effusion (TBE) and 32 cases of non-tuberculous exudative pleural effusion. Conclusive pathological diagnosis was made in 79.4% of the cases. For diagnosis of MPE, MT had a sensitivity of 89.1% (95% CI 80.4-94.3), specificity of 100% (95% CI 96.0-100.0), and positive predictive value (PPV) of 100% (95% CI 94.4-100) and negative predictive value (NPV) of 92.1% (95% CI 85.6-95.9). For TBE, MT had a sensitivity of 90.5% (95% CI 81.8-95.6), specificity of 100% (95% CI 96.3- 100.0) PPV of 100% (95% CI 94.1-100) and NPV of 93.9% (95% CI 88.0-97.2). Overall complication rate was 3.3%.

    CONCLUSIONS: MT showed excellent sensitivity and specificity in the diagnosis of exudative pleural effusion in this region. It reduces empirical therapy by providing histological evidence of disease when initial non-invasive investigations were inconclusive.

  9. Ch'ng ACW, Chan SK, Ignatius J, Lim TS
    Eur J Immunol, 2019 08;49(8):1186-1199.
    PMID: 30919413 DOI: 10.1002/eji.201747328
    The application of human TCR in cancer immunotherapy has gained momentum with developments in tumor killing strategies using endogenous adaptive immune responses. The successful coverage of a diverse TCR repertoire is mainly attributed to the primer design of the human TCR V genes. Here, we present a refined primer design strategy of the human TCR V gene by clustering V gene sequence homolog for degenerate primer design based on the data from IMGT. The primers designed were analyzed and the PCR efficiency of each primer set was optimized. A total of 112 alpha and 160 beta sequences were aligned and clustered using a phylogram yielding 32 and 27 V gene primers for the alpha and beta family. The new primer set was able to provide 93.75% and 95.63% coverage for the alpha and beta family, respectively. A semi-qualitative approach using the designed primer set was able to provide a relative view of the TCR V gene diversity in different populations. Taken together, the new primers provide a more comprehensive coverage of the TCR gene diversity for improved TCR library generation and TCR V gene analysis studies.
  10. Kho SS, Yong MC, Chan SK, Tie ST
    Thorax, 2018 10;73(10):994-995.
    PMID: 29599199 DOI: 10.1136/thoraxjnl-2018-211729
  11. Kho SS, Chan SK, Yong MC, Tie ST
    BMC Res Notes, 2017 Jul 21;10(1):304.
    PMID: 28732541 DOI: 10.1186/s13104-017-2635-4
    BACKGROUND: Massive hemoptysis is a common encounter in respiratory medicine. Bronchoscopy plays an important role in localizing the origin of bleeding, as well as endoscopic treatment of centrally located lesions. Endobronchial embolization is a novel technique enabling the management of hemoptysis arising even from peripheral lesions, via occlusion of the culprit bronchus, thereby securing the airway. Endobronchial Watanabe Spigot had been advocate in the treatment of bronchopleural fistula and the use of this novel technique had since then been expanded into the management of massive hemoptysis. To the best of our knowledge, this is the first reported case in Malaysia.

    CASE PRESENTATION: 78-year-old lady who presented with life-threatening hemoptysis leading rapidly to cardiac arrest upon arrival. Spontaneous circulation was restored after resuscitation with an urgent thoracic computed tomography angiogram revealed bleeding likely from the posterior basal segment of left lower lobe, with bronchiectatic changes. Urgent flexible bronchoscopy revealed airway flooding, with bleeding originating from the lingular and posterior-basal segment of the left lower lobe. Airway toileting was performed and two 7 mm Endobronchial Watanabe Spigots were plugged into the culprit bronchi. Urgent bronchial artery embolization was then attempted, but was unsuccessful. She was managed conservatively, as surgical resection was deemed high risk. The spigots were removed 4 days later uneventfully. There was no recurrence of hemoptysis, and patient remained well during 1-month follow up.

    CONCLUSIONS: The utmost priority in managing life-threatening hemoptysis is to prevent airway flooding. Endobronchial embolization with Endobronchial Watanabe Spigot is useful as a temporary measure before definitive therapy, or can itself be the main therapeutic player in the hemoptysis armament for high-risk patients.

  12. Chan SK, Kuzuya A, Choong YS, Lim TS
    SLAS Discov, 2019 01;24(1):68-76.
    PMID: 30063871 DOI: 10.1177/2472555218791743
    The inherent ability of nucleic acids to recognize a complementary pair has gained wide popularity in DNA sensor applications. DNA molecules can be produced in bulk and easily incorporated with various nanomaterials for sensing applications. More complex designs and sophisticated DNA sensors have been reported over the years to allow DNA detection in a faster, cheaper, and more convenient manner. Here, we report a DNA sensor designed to function like a switch to turn "on" silver nanocluster (AgNC) generation in the presence of a specific DNA target. By defining the probe region sequence, we are able to tune the color of the AgNC generated in direct relation to the different targets. As a proof of concept, we used dengue RNA-dependent RNA polymerase conserved sequences from all four serotypes as targets. This method was able to distinguish each dengue serotype by generating the serotype-respective AgNCs. The DNA switch was also able to identify and amplify the correct target in a mixture of targets with good specificity. This strategy has a detection limit of between 1.5 and 2.0 µM depending on the sequence of AgNC. The DNA switch approach provides an attractive alternative for single-target or multiplex DNA detection.
  13. Kho SS, Chan SK, Phui VE, Tie ST
    Breathe (Sheff), 2019 Jun;15(2):e62-e68.
    PMID: 31777566 DOI: 10.1183/20734735.0352-2018
    Acute chest pain and breathlessness in a haemodialysis patient is a common but challenging clinical scenario, can you diagnose and manage it? http://bit.ly/2Qf1mXr.
  14. Kho SS, Chan SK, Yong MC, Tie ST
    ERJ Open Res, 2019 Oct;5(4).
    PMID: 31649952 DOI: 10.1183/23120541.00135-2019
    Background: Radial endobronchial ultrasound (R-EBUS) is an effective technique in the diagnosis of peripheral pulmonary lesions (PPL). However, lesion orientation with regards to the radial probe remains an important factor for effective biopsy. "Within" orientation was associated with significantly higher diagnostic yield. Cryobiopsy is a novel technique in obtaining larger tissue samples with the frozen tip allowing biopsy in a 360° direction, thus potentially achieving more effective biopsy in eccentrically and adjacently orientated lesions. We aimed to evaluate the performance and safety of transbronchial cryobiopsy versus forceps biopsy in eccentrically and adjacently orientated R-EBUS lesions.

    Methods: Retrospective review of R-EBUS transbronchial biopsy for PPL over 17 months.

    Results: 114 R-EBUS scans were included for analysis during the study period. Forceps biopsy was performed in 76 (66.7%) cases and cryobiopsy in 38 (33.3%) cases. Baseline demographics and lesion characteristics did not differ between the two groups. Median (interquartile range) lesion size was 3.48 (2.63-4.51) cm. Overall, 41.2% of lesions were of eccentric orientation and 15.8% adjacent orientation; only 43% were concentric in orientation. Overall diagnostic yield was 67.5% (77 out of 114). Orientation remained an important factor affecting diagnostic yield. Transbronchial cryobiopsy significantly increased the diagnostic yield in eccentrically and adjacently orientated lesions to 75.0% (18 out of 24), compared to 48.8% (20 out of 41) obtained via forceps biopsy (p<0.05); but not in concentric lesions. Cryobiopsy was associated with more mild and moderate bleeding complications compared to the forceps biopsy group.

    Conclusions: Transbronchial cryobiopsy under R-EBUS guidance is a safe procedure which potentially increases diagnostic yield in eccentrically and adjacently orientated PPLs.

  15. Tong JWE, Kho SS, Chan SK, Tie ST
    Breathe (Sheff), 2022 Mar;18(1):220009.
    PMID: 36338255 DOI: 10.1183/20734735.0009-2022
    Clinicians should maintain a high level of clinical suspicion for invasive aspergillosis in patients receiving immunosuppression, as early diagnosis and treatment are essential to prevent significant morbidity and mortality https://bit.ly/3qLG9Yx.
  16. Kho SS, Chan SK, Yong MC, Tie ST
    Med J Malaysia, 2018 02;73(1):49-50.
    PMID: 29531204 MyJurnal
    Tuberculous pleural effusion (TBE) is a common encounter in our region. Up to 50% of patients with TBE will develop residual pleural thickening (RPT) which can lead to functional impairment. However, the need of drainage remains controversial. We report a case of end-stage renal failure patient who presented with right multiloculated tuberculous pleural effusion which was drained via a medical thoracoscope. Patient reports immediate relief of breathlessness post procedure and one month follow up shown significant improvement of RPT. We also discussed the current perspective on the rationale of TBE drainage and the role of medical thoracoscope in TBE management.
  17. Chan SK, Lai JY, Gan CY, Lim TS
    Food Chem, 2023 Mar 31;419:136070.
    PMID: 37030209 DOI: 10.1016/j.foodchem.2023.136070
    A higher specific activity of microbial transglutaminase (mTGase) is desirable for a broad range of applications ranging from food industry to biotechnology. Three-dimensional docking simulation of mTGase revealed that residues V65, W69, and Y75 were critical for substrate recognition. A semi-rational mutagenesis approach was applied to each residue to generate three separate mini mutant libraries. A high-throughput screening process identified five mutants that demonstrated improved specific activities than the wild type (WT) mTGase were isolated from the Y75 mini mutant library. Mutant Y75L showed approximately 60% increment in specific activity and improved substrate specificity. Conjugation of two heterologous single-chain fragment variable clones to generate a diabody with mutant Y75L was successfully performed and validated. This work demonstrates the successful application of semi-rational mutagenesis coupled with a high-throughput screening approach to identify mTGase mutants with improved specific activities and specificities which are beneficial for protein-protein conjugation.
  18. Chan SK, Rahumatullah A, Lai JY, Lim TS
    Adv Exp Med Biol, 2017;1053:35-59.
    PMID: 29549634 DOI: 10.1007/978-3-319-72077-7_3
    Many countries are facing an uphill battle in combating the spread of infectious diseases. The constant evolution of microorganisms magnifies the problem as it facilitates the re-emergence of old infectious diseases as well as promote the introduction of new and more deadly variants. Evidently, infectious diseases have contributed to an alarming rate of mortality worldwide making it a growing concern. Historically, antibodies have been used successfully to prevent and treat infectious diseases since the nineteenth century using antisera collected from immunized animals. The inherent ability of antibodies to trigger effector mechanisms aids the immune system to fight off pathogens that invades the host. Immune libraries have always been an important source of antibodies for infectious diseases due to the skewed repertoire generated post infection. Even so, the role and ability of naïve antibody libraries should not be underestimated. The naïve repertoire has its own unique advantages in generating antibodies against target antigens. This chapter will highlight the concept, advantages and application of human naïve libraries as a source to isolate antibodies against infectious disease target antigens.
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