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Fulltext Practice patterns of some gynaecologists in Malaysia with regards to prophylactic oophorectomy and hormone replacement therapy

Ravindran J, Leow CH

Med J Malaysia, 1996 Dec;51(4):409-14.
PMID: 10968026

This study aimed to look at the prevailing practice patterns of gynaecologists with regards to prophylactic oophorectomy and usage of hormone replacement therapy. Questionnaires were sent to the first 200 gynaecologists listed in the membership list of the Obstetrical and Gynaecological Society of Malaysia. The response rate was 30%. The results showed that most gynaecologists would perform prophylactic oophorectomy after the age of 49 years. The result was equivocal for the ages between 45 to 49 years. Of those who retained the ovaries at the age of 45 to the menopause, 55% did so because the ovaries were still functional. Almost all gynaecologists would prescribe hormone replacement therapy (HRT) after oophorectomy and the most commonly prescribed form was the oral type. Thirty-five per cent of gynaecologists claimed that more than 80% of their patients were compliant to HRT. The reasons perceived for the poor compliance were mainly poor knowledge and misconception.
Gemcitabine and carboplatin in the treatment of locally advanced and metastatic non-small cell lung cancer

Leow CH, Liam CK

Respirology, 2005 Nov;10(5):629-35.
PMID: 16268917

The aim of the study was to evaluate the response, survival advantage and toxicity profile of gemcitabine-carboplatin combination cytotoxic chemotherapy in patients with locally advanced and metastatic non-small cell lung cancer (NSCLC).
Advancements in the preparation and application of monolithic silica columns for efficient separation in liquid chromatography

Khoo HT, Leow CH

Talanta, 2021 Mar 01;224:121777.
PMID: 33379011 DOI: 10.1016/j.talanta.2020.121777

Fast and efficient separation remains a big challenge in high performance liquid chromatography (HPLC). The need for higher efficiency and resolution in separation is constantly in demand. To achieve that, columns developed are rapidly moving towards having smaller particle sizes and internal diameters (i.d.). However, these parameters will lead to high back-pressure in the system and will burden the pumps of the HPLC instrument. To address this limitation, monolithic columns, especially silica-based monolithic columns have been introduced. These columns are being widely investigated for fast and efficient separation of a wide range of molecules. The present article describes the current methods developed to enhance the column efficiency of particle packed columns and how silica monolithic columns can act as an alternative in overcoming the low permeability of particle packed columns. The fundamental processes behind the fabrication of the monolith including the starting materials and the silica sol-gel process will be discussed. Different monolith derivatization and end-capping processes will be further elaborated and followed by highlights of the performance such monolithic columns in key applications in different fields with various types of matrices.
Epidermal growth factor receptor targeted therapy with gefitinib in locally advanced and metastatic primary lung adenocarcinoma

Liam CK, Pang YK, Leow CH

Respirology, 2006 May;11(3):287-91.
PMID: 16635086

To describe the efficacy of monotherapy with the epidermal growth factor receptor-tyrosine kinase inhibitor, gefitinib in patients with locally advanced and metastatic primary lung adenocarcinoma.
Generation of soluble, disulfide-rich JEV NS1 protein recognizable by anti-NS1 antibodies through a simplified, in vitro refolding approach

Chong HY, Leow CY, Leow CH

Int J Biol Macromol, 2021 Aug 31;185:485-493.
PMID: 34174313 DOI: 10.1016/j.ijbiomac.2021.06.146

Co-existence of Japanese Encephalitis virus (JEV) with highly homologous antigenic epitopes results in antibody-based serodiagnosis being inaccurate at detecting and distinguishing JEV from other flaviviruses. This often causes misdiagnosis and inefficient treatments of flavivirus infection. Generation of JEV NS1 protein remains a challenge as it is notably expressed in the form of inactive aggregates known as inclusion bodies using bacterial expression systems. This study evaluated two trxB and gor E. coli strains in producing soluble JEV NS1 via a cold-shock expression system. High yield of JEV NS1 inclusion bodies was produced using cold-shocked expression system. Subsequently, a simplified yet successful approach in generating soluble, active JEV NS1 protein through solubilization, purification and in vitro refolding of JEV NS1 protein from inclusion bodies was developed. A step-wise dialysis refolding approach was used to facilitate JEV NS1 refolding. The authenticity of the refolded JEV NS1 was confirmed by specific antibody binding on indirect ELISA commercial anti-NS1 antibodies which showed that the refolded JEV NS1 was highly immunoreactive. This presented approach is cost-effective, and negates the need for mammalian or insect cell expression systems in order to synthesize this JEV NS1 protein of important diagnostic and therapeutic relevance in Japanese Encephalitis disease.
Fulltext Tracheobronchial stenting is safe and effective in relieving upper airway obstruction

Pang YK, Liam CK, Leow CH, Shyamala P, Zal AR

Med J Malaysia, 2006 Jun;61(2):147-50.
PMID: 16898303 MyJurnal

Many studies have shown that tracheobronchial stenting is effective in relieving respiratory distress secondary to major airway obstruction due to lung or oesophageal cancer. A retrospective review on the benefits and complications of self-expandable metallic stent (SEMS) insertion through flexible bronchoscopy for the palliative treatment of upper airway obstruction in University Malaya Medical Centre was performed. Ten patients underwent this procedure. Relief of dyspnoea was immediate following stent insertion in all patients. Stent migration occurred in one patient and three patients had restenosis of the central airway. We conclude that tracheobronchial stenting via flexible bronchoscopy is feasible and safe.
Flavivirus infection-A review of immunopathogenesis, immunological response, and immunodiagnosis

Chong HY, Leow CY, Abdul Majeed AB, Leow CH

Virus Res, 2019 12;274:197770.
PMID: 31626874 DOI: 10.1016/j.virusres.2019.197770

Flaviviruses are group of single stranded RNA viruses that cause severe endemic infection and epidemics on a global scale. It presents a significant health impact worldwide and the viruses have the potential to emerge and outbreak in a non-endemic geographical region. Effective vaccines for prophylaxis are only available for several flaviviruses such as Yellow Fever virus, Tick-borne Encephalitis Virus, Dengue Virus and Japanese Encephalitis Virus and there is no antiflaviviral agent being marketed. This review discusses the flavivirus genome, replication cycle, epidemiology, clinical presentation and pathogenesis upon infection. Effective humoral response is critical to confer protective immunity against flaviviruses. Hence, we have also highlighted the immune responses elicited upon infection, various diagnostic facilities available for flaviviral disease and monoclonal antibodies available to date against flavivirus infection.
Molecular characterization of Schistosoma mansoni tegument annexins and comparative analysis of antibody responses following parasite infection

Leow CY, Willis C, Leow CH, Hofmann A, Jones M

Mol Biochem Parasitol, 2019 12;234:111231.
PMID: 31628972 DOI: 10.1016/j.molbiopara.2019.111231

Schistosomes are parasitic blood flukes that infect approximately 250 million people worldwide. The disease known as schistosomiasis, is the second most significant tropical parasitic disease after malaria. Praziquantel is the only effective drug currently licensed for schistosomiasis and there are concerns about resistance to the drug. There has been much effort to develop vaccines against schistosomiasis to produce long-term protection in endemic regions. Surface-associated proteins, and in particular, those expressed in the body wall, or tegument, have been proposed as potential vaccine targets. Of these, annexins are thought to be of integral importance for the stability of this apical membrane system. Here, we present the structural and immunobiochemical characterization of four homologous annexins namely annexin B30, annexin B5a, annexin B7a and annexin B5b from S. mansoni. Bioinformatics analysis showed that there was no signal peptide predicted for any annexin in this study. Further analysis showed that each of all four annexin protein possesses a primary structure consisting of a short but variable N-terminal region and a long C-terminal core containing four homologous annexin repeats (I-IV), which contain five alpha-helices. The life cycle expression profile of each annexin was assessed using quantitative PCR. The results showed that the overall transcript levels of the each of four homologous annexins were relatively low in the egg stage, but increased gradually after the transition of cercariae (the invasive schistosome larvae) to schistosomula (the post-invasive larvae). Circular dichroism (CD) demonstrated that rAnnexin B30, rAnnexin B5a and rAnnexin 7a were folded, showing a secondary structure content rich in alpha-helices. The membrane binding affinity was enhanced when rAnnexin B30, rAnnexin B5a and rAnnexin 7a was incubated in the presence of Ca2+. All annexin members evaluated in this study were immunolocalized to the tegument, with immunoreactivity also occurring in cells and in muscle of adult parasites. All four recombinant annexins were immunoreactive and they were recognized by the sera of mice infected with S. mansoni. In conclusion, the overall results present the molecular characterization of annexin B30, annexin B5a, annexin B7a and annexin B5b from S. mansoni in host-parasite interactions and strongly suggest that the molecules could be useful candidates for vaccine or diagnostic development.
Insights into the chicken IgY with emphasis on the generation and applications of chicken recombinant monoclonal antibodies

Lee W, Syed Atif A, Tan SC, Leow CH

J Immunol Methods, 2017 08;447:71-85.
PMID: 28502720 DOI: 10.1016/j.jim.2017.05.001

The advantages of chicken (Gallus gallus domesticus) antibodies as immunodiagnostic and immunotherapeutic biomolecules has only been recently recognized. Even so, chicken antibodies remain less-well characterized than their mammalian counterparts. This review aims at providing a current overview of the structure, function, development and generation of chicken antibodies. Additionally, brief but comprehensive insights into current knowledge pertaining to the immunogenetic framework and diversity-generation of the chicken immunoglobulin repertoire which have contributed to the establishment of recombinant chicken mAb-generating methods are discussed. Focus is provided on the current methods used to generate antibodies from chickens with added emphasis on the generation of recombinant chicken mAbs and its derivative formats. The advantages and limitations of established protocols for the generation of chicken mAbs are highlighted. The various applications of recombinant chicken mAbs and its derivative formats in immunodiagnostics and immunotherapy are further detailed.
Immunogenicity, antibody responses and vaccine efficacy of recombinant annexin B30 against Schistosoma mansoni

Leow CY, Willis C, Chuah C, Leow CH, Jones M

Parasite Immunol., 2020 03;42(3):e12693.
PMID: 31880816 DOI: 10.1111/pim.12693

AIMS: Schistosomes infect approximately 250 million people worldwide. To date, there is no effective vaccine available for the prevention of schistosome infection in endemic regions. There remains a need to develop means to confer long-term protection of individuals against reinfection. In this study, an annexin, namely annexin B30, which is highly expressed in the tegument of Schistosoma mansoni was selected to evaluate its immunogenicity and protective efficacy in a mouse model.
METHODS AND RESULTS: Bioinformatics analysis showed that there were three potential linear B-cell epitopes and four conformational B-cell epitopes predicted from annexin B30, respectively. Full-length annexin B30 was cloned and expressed in Escherichia coli BL21(DE3). In the presence of adjuvants, the soluble recombinant protein was evaluated for its protective efficacy in two independent vaccine trials. Immunization of CBA mice with recombinant annexin B30 formulated either in alum only or alum/CpG induced a mixed Th1/Th2 cytokine profile but no significant protection against schistosome infection was detected.
CONCLUSION: Recombinant annexin B30 did not confer significant protection against the parasite. The molecule may not be suitable for vaccine development. However, it could be an ideal biomarker recommended for immunodiagnostics development.
Fulltext Diagnostic and therapeutic potential of shark variable new antigen receptor (VNAR) single domain antibody

Cheong WS, Leow CY, Abdul Majeed AB, Leow CH

Int J Biol Macromol, 2020 Mar 15;147:369-375.
PMID: 31926922 DOI: 10.1016/j.ijbiomac.2020.01.039

Conventional monoclonal antibodies (mAbs) have been widely used in research and diagnostic applications due to their high affinity and specificity. However, multiple limitations, such as large size, complex structure and sensitivity to extreme ambient temperature potentially weaken the performance of mAbs in certain applications. To address this problem, the exploration of new antigen binders is extensively required in relation to improve the quality of current diagnostic platforms. In recent years, a new immunoglobulin-based protein, namely variable domain of new antigen receptor (VNAR) was discovered in sharks. Unlike conventional mAbs, several advantages of VNARs, include small size, better thermostability and peculiar paratope structure have attracted interest of researchers to further explore on it. This article aims to first present an overview of the shark VNARs and outline the characteristics as an outstanding new reagent for diagnostic and therapeutic applications.
Exploring shark VNAR antibody against infectious diseases using phage display technology

Lim HT, Kok BH, Leow CY, Leow CH

Fish Shellfish Immunol, 2023 Sep;140:108986.
PMID: 37541634 DOI: 10.1016/j.fsi.2023.108986

Antibody with high affinity and specificity to antigen has widely used as a tool to combat various diseases. The variable domain of immunoglobulin new antigen receptor (VNAR) naturally found in shark contains autonomous function as single-domain antibody. Due to its excellent characteristics, the small, non-complex, and highly stable have made shark VNAR can acquires the antigen-binding capability that might not be reached by conventional antibody. Phage display technology enables shark VNAR to be presented on the surface of phage, allowing the exploration of shark VNAR as an alternative antibody format to target antigens from various infectious diseases. The application of phage-displayed shark VNAR in antibody library and biopanning eventually leads to the discovery and isolation of antigen-specific VNARs with diagnostic and therapeutic potential towards infectious diseases. This review provides an overview of the shark VNAR antibody, the types of phage display technology with comparison to the other types of display system, as well as the application and case studies of phage-displayed shark VNAR antibodies against infectious diseases.
Magnetophoresis of iron oxide nanoparticles at low field gradient: the role of shape anisotropy

Lim J, Yeap SP, Leow CH, Toh PY, Low SC

J Colloid Interface Sci, 2014 May 1;421:170-7.
PMID: 24594047 DOI: 10.1016/j.jcis.2014.01.044

Magnetophoresis of iron oxide magnetic nanoparticle (IOMNP) under low magnetic field gradient (<100 T/m) is significantly enhanced by particle shape anisotropy. This unique feature of magnetophoresis is influenced by the particle concentration and applied magnetic field gradient. By comparing the nanosphere and nanorod magnetophoresis at different concentration, we revealed the ability for these two species of particles to achieve the same separation rate by adjusting the field gradient. Under cooperative magnetophoresis, the nanorods would first go through self- and magnetic field induced aggregation followed by the alignment of the particle clusters formed with magnetic field. Time scale associated to these two processes is investigated to understand the kinetic behavior of nanorod separation under low field gradient. Surface functionalization of nanoparticles can be employed as an effective strategy to vary the temporal evolution of these two aggregation processes which subsequently influence the magnetophoretic separation time and rate.
Changes in the distribution of lung cancer cell types and patient demography in a developing multiracial Asian country: experience of a university teaching hospital

Liam CK, Pang YK, Leow CH, Poosparajah S, Menon A

Lung Cancer, 2006 Jul;53(1):23-30.
PMID: 16690159

A comparison of patients with lung cancer diagnosed at the University of Malaya Medical Centre, Kuala Lumpur, Malaysia from October 1991 to September 1999 with another group of lung cancer patients diagnosed at the same hospital during an earlier period of 1967-1976 was undertaken to determine whether there had been a change in the distribution of lung cancer cell types and patient demography. The number of histologically and/or cytologically proven lung cancer cases was 583 from October 1991 to September 1999 and 278 from 1967 to 1976. The mean (S.D.) age of the patients during the period 1991-1999, 60.1 (12.0) years was similar to that of patients during the period 1967-1976, 60.3 (12.2) years. There was no shift of the peak age distribution of lung cancer (i.e., the 7th decade) between the two periods. In the recent period, the percentage of patients with adenocarcinoma had increased significantly to 43.2% from 25.2% while that of large cell carcinoma had decreased to 3.3% from 11.9%. The percentages of patients with squamous cell carcinoma (SCC) and small cell lung cancer remained stable. In the period 1967-1976, SCC was the commonest cell type in men and in smokers while adenocarcinoma was the commonest cell type in women and in never smokers. In the period 1991-1999, adenocarcinoma was the commonest cell type in both men and women as well as in smokers and never smokers.
Analysis of differentially expressed proteins in cancerous and normal colonic tissues

Gam LH, Leow CH, Man CN, Gooi BH, Singh M

World J Gastroenterol, 2006 Aug 21;12(31):4973-80.
PMID: 16937492

AIM: To identify and analyze the differentially expressed proteins in normal and cancerous tissues of four patients suffering from colon cancer.
METHODS: Colon tissues (normal and cancerous) were homogenized and the proteins were extracted using three protein extraction buffers. The extraction buffers were used in an orderly sequence of increasing extraction strength for proteins with hydrophobic properties. The protein extracts were separated using the SDS-PAGE method and the images were captured and analyzed using Quantity One software. The target protein bands were subjected to in-gel digestion with trypsin and finally analyzed using an ESI-ion trap mass spectrometer.
RESULTS: A total of 50 differentially expressed proteins in colonic cancerous and normal tissues were identified.
CONCLUSION: Many of the identified proteins have been reported to be involved in the progression of similar or other types of cancers. However, some of the identified proteins have not been reported before. In addition, a number of hypothetical proteins were also identified.
Plasmodium falciparum protein kinase as a potential therapeutic target for antimalarial drugs development

Mahmud F, Lee PC, Abdul Wahab H, Mustaffa KMF, Leow CH, Azhar R, et al.

Trop Biomed, 2020 Sep 01;37(3):822-841.
PMID: 33612795 DOI: 10.47665/tb.37.3.822

Malaria is one of the most dangerous infectious diseases due to its high infection and mortality rates, especially in the tropical belt. Plasmodium falciparum (P. falciparum), the most virulent malaria parasite in humans, was recently reported to develop resistance against the final efficient antimalarial drug, artemisinin. Little is known about the resistance mechanisms, which further complicates the problem as a proper counteraction is unable to be taken. Hence, the understanding of drug mode of action and its molecular target is valuable knowledge that needs to be considered to develop the next generation of antimalarial drugs. P. falciparum protein kinase (Pf PK) is an attractive target for antimalarial chemotherapy due to its vital roles in all P. falciparum life stages. Moreover, overall structural differences and the presence of unique Pf PKs that are absent in human kinome, suggesting specific inhibition of Pf PK without affecting human cells is achievable. To date, at least 86 eukaryotic protein kinases have been identified in P. falciparum kinome, by which less than 40 were validated as potential targets at the erythrocytes stage. In this review, recent progress of the furthest validated Pf PKs; Pf Nek-1, Pf CDPK1, Pf CDPK4, Pf PKG, and Pf CLK-3 will be briefly discussed.
Isolation and characterization of a novel anti-salbutamol chicken scFv for human doping urinalysis

Lee W, Syed A A, Leow CY, Tan SC, Leow CH

Anal Biochem, 2018 08 15;555:81-93.
PMID: 29775561 DOI: 10.1016/j.ab.2018.05.009

Anti-salbutamol antibodies remain as important tools for the detection of salbutamol abuse in athletic doping. This study evaluated the feasibility and efficiency of the chicken (Gallus gallus domesticus) as an immunization host to generate anti-salbutamol scFv antibodies by phage display. A phage display antibody library was constructed from a single chicken immunized against salbutamol-KLH conjugate. After a stringent biopanning strategy, a novel scFv clone which was inhibited by free salbutamol recorded the highest affinity. This scFv was expressed as soluble and functional protein in Escherichia coli T7 SHuffle Express B (DE3) strain. Cross-reactivity studies of the scFv towards other relevant β2-agonists revealed that the scFv cross-reacted significantly towards clenbuterol. The determined IC50 of the scFv towards the two β2-agonists were; IC50 salbutamol = ∼0.310 μg/ml, IC50 clenbuterol = ∼0.076 μg/ml. The generated scFv demonstrated poor stability based on accelerated stability studies. The scFv was used to develop an competitive indirect ELISA (LOD = 0.125 μg/ml) for detection of parent salbutamol in spiked human urine (n = 18) with ∼83.4% reliability at the cut-off of 1 μg/ml currently implemented by WADA and may be of potential use in human doping urinalysis.
Differential expression of cytokine genes in THP-1-derived macrophages infected with mild and virulence strains of Shigella flexneri 2a

Shabani NRM, Mokhtar M, Leow CH, Lean QY, Chuah C, Singh KKB, et al.

Infect Genet Evol, 2020 11;85:104532.
PMID: 32911076 DOI: 10.1016/j.meegid.2020.104532

Shigella is an intracellular bacterial pathogen that causes bacterial dysentery called shigellosis. The assessment of pro- and anti-inflammatory mediators produced by immune cells against this bacteria are vital in identifying the effectiveness of the immune reaction in protecting the host. In Malaysia, Shigella is ranked as the third most common bacteria causing diarrheal disease among children below 5 years old. In the present study, we aim to examine the differential cytokine gene expressions of macrophages in response to two types of clinical strains of Shigella flexneri 2a (S. flexneri 2a) isolated from patients admitted in Hospital Universiti Sains Malaysia, Kelantan, Malaysia. THP-1-derived macrophages, as the model of human macrophages, were infected separately with S. flexneri 2a mild (SH062) and virulence (SH057) strains for 6, 12, and 24 h, respectively. The gene expression level of inflammatory mediators was identified using real-time quantitative polymerase chain reaction (RT-qPCR). The production of nitric oxide (NO) by the macrophages was measured by using a commercialized NO assay kit. The ability of macrophages to kill the intracellular bacteria was assessed by intracellular killing assay. Induction of tumor necrosis factor-alpha (TNFα), interleukin (IL)-1β, IL-6, IL-12, inducible NO synthase (iNOS), and NO, confirmed the pro-inflammatory reaction of the THP-1-derived macrophages in response to S. flexneri 2a, especially against the SH507 strain. The SH057 also induced a marked increase in the expression levels of the anti-inflammatory cytokine mRNAs at 12 h and 24 h post-infection. In the intracellular killing assay, both strains showed less viable, indicating the generation of pro-inflammatory cytokines in the presence of iNOS and NO was crucial in the stimulation of macrophages for the host defense against shigellosis. Transcription analysis of THP-1-derived macrophages in this study identifies differentially expressed cytokine genes that correlated with the virulence factor of S. flexneri 2a.
Application of Reverse Vaccinology and Immunoinformatic Strategies for the Identification of Vaccine Candidates Against Shigella flexneri

Leow CY, Chuah C, Abdul Majeed AB, Mohd Nor N, Leow CH

Methods Mol Biol, 2022;2414:17-35.
PMID: 34784029 DOI: 10.1007/978-1-0716-1900-1_2

Reverse vaccinology (RV) was first introduced by Rappuoli for the development of an effective vaccine against serogroup B Neisseria meningitidis (MenB). With the advances in next generation sequencing technologies, the amount of genomic data has risen exponentially. Since then, the RV approach has widely been used to discover potential vaccine protein targets by screening whole genome sequences of pathogens using a combination of sophisticated computational algorithms and bioinformatic tools. In contrast to conventional vaccine development strategies, RV offers a novel method to facilitate rapid vaccine design and reduces reliance on the traditional, relatively tedious, and labor-intensive approach based on Pasteur"s principles of isolating, inactivating, and injecting the causative agent of an infectious disease. Advances in biocomputational techniques have remarkably increased the significance for the rapid identification of the proteins that are secreted or expressed on the surface of pathogens. Immunogenic proteins which are able to induce the immune response in the hosts can be predicted based on the immune epitopes present within the protein sequence. To date, RV has successfully been applied to develop vaccines against a variety of infectious pathogens. In this chapter, we apply a pipeline of bioinformatic programs for identification of Shigella flexneri potential vaccine candidates as an illustration immunoinformatic tools available for RV.
Fulltext Current progress of immunoinformatics approach harnessed for cellular- and antibody-dependent vaccine design

Kazi A, Chuah C, Majeed ABA, Leow CH, Lim BH, Leow CY

Pathog Glob Health, 2018 05;112(3):123-131.
PMID: 29528265 DOI: 10.1080/20477724.2018.1446773

Immunoinformatics plays a pivotal role in vaccine design, immunodiagnostic development, and antibody production. In the past, antibody design and vaccine development depended exclusively on immunological experiments which are relatively expensive and time-consuming. However, recent advances in the field of immunological bioinformatics have provided feasible tools which can be used to lessen the time and cost required for vaccine and antibody development. This approach allows the selection of immunogenic regions from the pathogen genomes. The ideal regions could be developed as potential vaccine candidates to trigger protective immune responses in the hosts. At present, epitope-based vaccines are attractive concepts which have been successfully trailed to develop vaccines which target rapidly mutating pathogens. In this article, we provide an overview of the current progress of immunoinformatics and their applications in the vaccine design, immune system modeling and therapeutics.

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