Displaying publications 1 - 20 of 39 in total

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  1. Lee WC, Mokhtar SS, Munisamy S, Yahaya S, Rasool AHG
    Cell Mol Biol (Noisy-le-grand), 2018 May 30;64(7):60-69.
    PMID: 29974854
    Diabetes mellitus is an epidemic that is gaining global concern. Chronic hyperglycemia in diabetes induces the excess production of free radicals. The deleterious effects of excess free radicals are encountered by endogenous antioxidant defense system. Imbalance between free radicals production and antioxidants defense mechanisms leads to a condition known as "oxidative stress". Diabetes mellitus is associated with augmented oxidative stress that induced micro- and macrovascular complications, which presents a significant risk for cardiovascular events. Low vitamin D levels in the body have also been reported to be associated with the pathogenesis of diabetes and enhanced oxidative stress. The article is to review available literature and summarize the relationship between oxidative stress and vitamin D levels in diabetes. We also review the effects of vitamin D analogs supplementation in improving oxidative stress in diabetics.
  2. Kim DY, Toan BN, Tan CK, Hasan I, Setiawan L, Yu ML, et al.
    Clin Mol Hepatol, 2023 Apr;29(2):277-292.
    PMID: 36710606 DOI: 10.3350/cmh.2022.0212
    Even though the combined use of ultrasound (US) and alpha-fetoprotein (AFP) is recommended for the surveillance of hepatocellular carcinoma (HCC), the utilization of AFP has its challenges, including accuracy dependent on its cut-off levels, degree of liver necroinflammation, and etiology of liver disease. Though various studies have demonstrated the utility of protein induced by vitamin K absence II (PIVKA-II) in surveillance, treatment monitoring, and predicting recurrence, it is still not recommended as a routine biomarker test. A panel of 17 experts from Asia-Pacific, gathered to discuss and reach a consensus on the clinical usefulness and value of PIVKA-II for the surveillance and treatment monitoring of HCC, based on six predetermined statements. The experts agreed that PIVKA-II was valuable in the detection of HCC in AFP-negative patients, and could potentially benefit detection of early HCC in combination with AFP. PIVKA-II is clinically useful for monitoring curative and intra-arterial locoregional treatments, outcomes, and recurrence, and could potentially predict microvascular invasion risk and facilitate patient selection for liver transplant. However, combining PIVKA-II with US and AFP for HCC surveillance, including small HCC, still requires more evidence, whilst its role in detecting AFP-negative HCC will potentially increase as more patients are treated for hepatitis-related HCC. PIVKA-II in combination with AFP and US has a clinical role in the Asia-Pacific region for surveillance. However, implementation of PIVKA-II in the region will have some challenges, such as requiring standardization of cut-off values, its cost-effectiveness and improving awareness among healthcare providers.
  3. Chen FS, Chen CC, Tsai CC, Lu JH, You HL, Chen CM, et al.
    Front Endocrinol (Lausanne), 2023;14:1173449.
    PMID: 37334296 DOI: 10.3389/fendo.2023.1173449
    BACKGROUND: Organophosphate flame retardants (OPFRs) are widely distributed in the environment and their metabolites are observed in urine, but little is known regarding OPFRs in a broad-spectrum young population from newborns to those aged 18 years.

    OBJECTIVES: Investigate urinary levels of OPFRs and OPFR metabolites in Taiwanese infants, young children, schoolchildren, and adolescents within the general population.

    METHODS: Different age groups of subjects (n=136) were recruited from southern Taiwan to detect 10 OPFR metabolites in urine samples. Associations between urinary OPFRs and their corresponding metabolites and potential health status were also examined.

    RESULTS: The mean level of urinary Σ10 OPFR in this broad-spectrum young population is 2.25 μg/L (standard deviation (SD) of 1.91 μg/L). Σ10 OPFR metabolites in urine are 3.25 ± 2.84, 3.06 ± 2.21, 1.75 ± 1.10, and 2.32 ± 2.29 μg/L in the age groups comprising of newborns, 1-5 year-olds, 6-10 year-olds, and 11-18 year-olds, respectively, and borderline significant differences were found in the different age groups (p=0.125). The OPFR metabolites of TCEP, BCEP, DPHP, TBEP, DBEP, and BDCPP predominate in urine and comprise more than 90% of the total. TBEP was highly correlated with DBEP in this population (r=0.845, p<0.001). The estimated daily intake (EDI) of Σ5OPFRs (TDCPP, TCEP, TBEP, TNBP, and TPHP) was 2,230, 461, 130, and 184 ng/kg bw/day for newborns, 1-5 yr children, 6-10 yr children, and 11-17 yr adolescents, respectively. The EDI of Σ5OPFRs for newborns was 4.83-17.2 times higher than the other age groups. Urinary OPFR metabolites are significantly correlated with birth length and chest circumference in newborns.

    CONCLUSION: To our knowledge, this is the first investigation of urinary OPFR metabolite levels in a broad-spectrum young population. There tended to be higher exposure rates in both newborns and pre-schoolers, though little is known about their exposure levels or factors leading to exposure in the young population. Further studies should clarify the exposure levels and factor relationships.

  4. Lee WC, Anton BP, Wang S, Baybayan P, Singh S, Ashby M, et al.
    BMC Genomics, 2015;16:424.
    PMID: 26031894 DOI: 10.1186/s12864-015-1585-2
    The genome of the human gastric pathogen Helicobacter pylori encodes a large number of DNA methyltransferases (MTases), some of which are shared among many strains, and others of which are unique to a given strain. The MTases have potential roles in the survival of the bacterium. In this study, we sequenced a Malaysian H. pylori clinical strain, designated UM032, by using a combination of PacBio Single Molecule, Real-Time (SMRT) and Illumina MiSeq next generation sequencing platforms, and used the SMRT data to characterize the set of methylated bases (the methylome).
  5. Ng YL, Lee WC, Lau YL, Fong MY
    Trop Med Infect Dis, 2023 Jan 10;8(1).
    PMID: 36668963 DOI: 10.3390/tropicalmed8010056
    Plasmodium knowlesi has emerged as an important zoonotic parasite that causes persistent symptomatic malaria in humans. The signs and symptoms of malaria are attributed to the blood stages of the parasites, which start from the invasion of erythrocytes by the blood stage merozoites. The apical membrane protein 1 (AMA-1) plays an important role in the invasion. In this study, we constructed and expressed recombinant PkAMA-1 domain II (PkAMA-1-DII) representing the predominant haplotypes from Peninsular Malaysia and Malaysian Borneo and raised specific antibodies against the recombinant proteins in rabbits. Despite the minor amino acid sequence variation, antibodies raised against haplotypes from Peninsular Malaysia and Malaysian Borneo demonstrated different invasion inhibition (46.81% and 39.45%, respectively) to P. knowlesi A1-H.1, a reference strain derived from Peninsular Malaysia. Here, we demonstrated how a minor variation in a conserved parasite protein could cast a significant impact on parasite invasion biology, suggesting a complex host-switching of P. knowlesi from different locations. This may challenge the implementation of a standardized One Health approach against the transmission of knowlesi malaria.
  6. Lee WC, Khoo BE, Bin Abdullah AF, Abdul Aziz ZB
    J Forensic Sci, 2013 May;58(3):658-63.
    PMID: 23488634 DOI: 10.1111/1556-4029.12103
    Bloodstain photography is important in forensic applications, especially for bloodstain pattern analysis. This study compares the enhancement effect of bloodstain photography using three different types of light source: fluorescent white light, near-ultraviolet (UV) light-emitting diode (LED) light, and 410 nm LED light. Randomized complete block designs were implemented to identify the lighting that would statistically produce the best enhancement results for bloodstains on different types of surfaces. Bloodstain samples were prepared on white cotton, brown carpet, tar road, and wood. These samples were photographed in darkroom conditions using a Canon EOS 50D digital SLR camera, with Canon EFS 60 mm f/2.8 Macro USM lens. Two-way analysis of variance and Fisher's least significant difference test were used to analyze the contrast of the images. The statistical analysis showed that 410 nm light is the best among the tested lights for enhancing bloodstains on the tested surfaces, where the contrast of bloodstain to background was the highest.
  7. van Enter BJD, Lau YL, Ling CL, Watthanaworawit W, Sukthana Y, Lee WC, et al.
    Am J Trop Med Hyg, 2017 Jul;97(1):232-235.
    PMID: 28719309 DOI: 10.4269/ajtmh.16-0999
    Toxoplasma gondii primary infection in pregnancy is associated with poor obstetric outcomes. This study aimed to determine the seroprevalence of Toxoplasma infection in pregnant migrant and refugee women from Myanmar attending antenatal care in Thailand. A random selection of 199 residual blood samples from first antenatal screen in 2014-2015 was tested for Toxoplasma IgG and IgM antibodies. Seroprevalence of Toxoplasma infection was 31.7% (95% confidence interval = 25.6-38.4). Avidity testing in the three positive IgM cases indicated all were past infections. Multiparity (≥ 3 children) was significantly associated with higher Toxoplasma seropositivity rates. Seroprevalence of T. gondii infection in this pregnant population is similar to the only other report from Myanmar, where multiparity was also identified as a significant association. Toxoplasma infection is important in pregnant women. Nevertheless, in this marginalized population, this infection may be given less priority, due to resource constraints in providing the most basic components of safe motherhood programs.
  8. Lee WC, Russell B, Lau YL, Nosten F, Rénia L
    Am J Trop Med Hyg, 2022 Apr 11;106(6):1670-4.
    PMID: 35405642 DOI: 10.4269/ajtmh.21-1229
    In malaria, rosetting is a phenomenon involving the cytoadherence of uninfected erythrocytes to infected erythrocytes (IRBC) harboring the late erythrocytic stage of Plasmodium spp. Recently, artesunate-stimulated rosetting has been demonstrated to confer a survival advantage to P. falciparum late-stage IRBC. This study investigated the rosetting response of P. falciparum and P. vivax clinical isolates to ex vivo antimalarial treatments. Brief exposure of IRBC to chloroquine, mefloquine, amodiaquine, quinine, and lumefantrine increased the rosetting rates of P. falciparum and P. vivax. Furthermore, the ex vivo combination of artesunate with mefloquine and piperaquine also resulted in increased the rosetting rates. Drug-mediated rosette-stimulation has important implications for the therapeutic failure of rapidly cleared drugs such as artesunate. However, further work is needed to establish the ramifications of increased rosetting rates by drugs with longer half-lifves, such as chloroquine, mefloquine, and piperaquine.
  9. Zhang R, Lee WC, Lau YL, Albrecht L, Lopes SC, Costa FT, et al.
    PLoS Negl Trop Dis, 2016 08;10(8):e0004912.
    PMID: 27509168 DOI: 10.1371/journal.pntd.0004912
    Malaria parasites dramatically alter the rheological properties of infected red blood cells. In the case of Plasmodium vivax, the parasite rapidly decreases the shear elastic modulus of the invaded RBC, enabling it to avoid splenic clearance. This study highlights correlation between rosette formation and altered membrane deformability of P. vivax-infected erythrocytes, where the rosette-forming infected erythrocytes are significantly more rigid than their non-rosetting counterparts. The adhesion of normocytes to the PvIRBC is strong (mean binding force of 440pN) resulting in stable rosette formation even under high physiological shear flow stress. Rosetting may contribute to the sequestration of PvIRBC schizonts in the host microvasculature or spleen.
  10. Lee WC, Yusof MM, Lau FN, Phua VC
    Asian Pac J Cancer Prev, 2013;14(6):3941-4.
    PMID: 23886211
    BACKGROUND: The use of preoperative chemoirradiation is the commonest treatment strategy employed in Malaysia for locally advanced rectal cancer. We need to determine the local control and survival rates for comparison with established rates in the literature.

    MATERIALS AND METHODS: This retrospective study analyzed all newly diagnosed patients with rectal adenocarcinoma who underwent long course preoperative radiotherapy (RT) at the Department of Radiotherapy and Oncology, Kuala Lumpur Hospital (HKL) between 1st January 2004 and 31st December 2010. The aim of the study was to determine the radiological response post radiotherapy, pathological response including circumferential resection margin (CRM) status, 3 years local control, 3 years overall survival (OS) and 3 years disease free survival (DFS). Statistical analysis was performed using the SPSS software. Kaplan-Meier and log rank analysis were used to determine survival outcomes.

    RESULTS: A total of 507 patients with rectal cancer underwent RT at HKL. Sixty seven who underwent long course preoperative RT were eligible for this study. The median age at diagnosis was 60 years old with a range of 26-78 years. The median tumour location was 6 cm from the anal verge. Most patients had suspicion of mesorectum involvement (95.5%) while 28.4% of patients had enlarged pelvic nodes on staging CT scan. All patients underwent preoperative chemo-irradiation except for five who had preoperative RT alone. Only 38 patients underwent definitive surgery (56.7%). Five patients were deemed to be inoperable radiologically and 3 patients were found to have unresectable disease intraoperatively. The remaining 21 patients defaulted surgery (31.3%). The median time from completion of RT to surgery was 8 weeks (range 5.6 to 29.4 weeks). Fifteen patients (39.5%) had surgery more than 8 weeks after completion of RT. Complete pathological response was noted in 4 patients (10.5%). The pathological CRM positive rate after RT was 18.4%. With a median follow-up of 38.8 months, the 3 year local control rate was 67%. The 3 years rate for CRM positive (<2 mm), CRM clear (>2 mm) and pCR groups were 0%, 88.1% and 100% respectively (p-value of 0.007). The 3 year OS and DFS were 57.3% and 44.8% respectively.

    CONCLUSIONS: In conclusion, the approach of long course preoperative chemoirradiation for rectal cancer needs to be re-examined in our local setting. The high rate of local recurrence is worrying and is mainly due to patient defaulting post-preoperative chemoirradiation or delayed definitive surgery.
  11. Lee WC, Russell B, Sobota RM, Ghaffar K, Howland SW, Wong ZX, et al.
    Elife, 2020 02 18;9.
    PMID: 32066522 DOI: 10.7554/eLife.51546
    In malaria, rosetting is described as a phenomenon where an infected erythrocyte (IRBC) is attached to uninfected erythrocytes (URBC). In some studies, rosetting has been associated with malaria pathogenesis. Here, we have identified a new type of rosetting. Using a step-by-step approach, we identified IGFBP7, a protein secreted by monocytes in response to parasite stimulation, as a rosette-stimulator for Plasmodium falciparum- and P. vivax-IRBC. IGFBP7-mediated rosette-stimulation was rapid yet reversible. Unlike type I rosetting that involves direct interaction of rosetting ligands on IRBC and receptors on URBC, the IGFBP7-mediated, type II rosetting requires two additional serum factors, namely von Willebrand factor and thrombospondin-1. These two factors interact with IGFBP7 to mediate rosette formation by the IRBC. Importantly, the IGFBP7-induced type II rosetting hampers phagocytosis of IRBC by host phagocytes.
  12. Lee WC, Russell B, Lee B, Chu CS, Phyo AP, Sriprawat K, et al.
    EBioMedicine, 2021 Nov;73:103680.
    PMID: 34749300 DOI: 10.1016/j.ebiom.2021.103680
    BACKGROUND: Artemisinin (ART) resistance in Plasmodium falciparum is thought to occur during the early stage of the parasite's erythrocytic cycle. Here, we identify a novel factor associated with the late stage parasite development that contributes to ART resistance.

    METHODS: Rosetting rates of clinical isolates pre- and post- brief (one hour) exposure to artesunate (AS, an ART derivative) were evaluated. The effects of AS-mediated rosetting on the post-AS-exposed parasite's replication and survival, as well as the extent of protection by AS-mediated rosetting on different parasite stages were investigated. The rosetting ligands, mechanisms, and gene mutations involved were studied.

    FINDINGS: Brief AS exposure stimulated rosetting, with AS-resistant isolates forming more rosettes in a more rapid manner. AS-mediated rosetting enabled infected erythrocytes (IRBC) to withstand AS exposure for several hours and protected the IRBC from phagocytosis. When their rosetting ability was blocked experimentally, the post-AS exposure survival advantage by the AS-resistant parasites was abrogated. Deletions in two genes coding for PfEMP1 exon 2 (PF3D7_0200300 and PF3D7_0223300) were found to be associated with AS-mediated rosetting, and these mutations were significantly selected through time in the parasite population under study, along with the K13 mutations, a molecular marker of ART-resistance.

    INTERPRETATION: Rapid ART parasite clearance is driven by the direct oxidative damages on IRBC by ART and the phagocytic destruction of the damaged IRBC. Rosetting serves as a rapid 'buying time' strategy that allows more parasites to complete schizont maturation, reinvasion and subsequent development into the intrinsically less ART-susceptible ring stage.

    FUNDING: A*STAR, NMRC-OF-YIRG, HRC e-ASIA, Wellcome.

  13. Sum JS, Lee WC, Amir A, Braima KA, Jeffery J, Abdul-Aziz NM, et al.
    Parasit Vectors, 2014;7:309.
    PMID: 24993022 DOI: 10.1186/1756-3305-7-309
    Molecular techniques are invaluable for investigation on the biodiversity of Anopheles mosquitoes. This study aimed at investigating the spatial-genetic variations among Anopheles mosquitoes from different areas of Peninsular Malaysia, as well as deciphering evolutionary relationships of the local Anopheles mosquitoes with the mosquitoes from neighbouring countries using the anopheline ITS2 rDNA gene.
  14. Wong ML, Zulzahrin Z, Vythilingam I, Lau YL, Sam IC, Fong MY, et al.
    Front Microbiol, 2023;14:1135977.
    PMID: 37025644 DOI: 10.3389/fmicb.2023.1135977
    The complex transmission profiles of vector-borne zoonoses (VZB) and vector-borne infections with animal reservoirs (VBIAR) complicate efforts to break the transmission circuit of these infections. To control and eliminate VZB and VBIAR, insecticide application may not be conducted easily in all circumstances, particularly for infections with sylvatic transmission cycle. As a result, alternative approaches have been considered in the vector management against these infections. In this review, we highlighted differences among the environmental, chemical, and biological control approaches in vector management, from the perspectives of VZB and VBIAR. Concerns and knowledge gaps pertaining to the available control approaches were discussed to better understand the prospects of integrating these vector control approaches to synergistically break the transmission of VZB and VBIAR in humans, in line with the integrated vector management (IVM) developed by the World Health Organization (WHO) since 2004.
  15. Lee WC, Chua T
    Malays Orthop J, 2021 Mar;15(1):138-140.
    PMID: 33880163 DOI: 10.5704/MOJ.2103.023
    Atypical femoral fractures (AFF) have low union rates. The use of teriparatide has been advocated for the post-operative healing of AFF, but the evidence is limited to case reports and some series due to its low incidence. We present a case series of four female patients to support the use of teriparatide after the surgical fixation of their AFF. Three of the patients had a complete AFF and one had an incomplete fracture. Their mean age was 70 (52 - 87) years, mean body mass index 24.6 (18.3 - 29.3), mean bone mineral density T-score of -2.3 (-4.8/-1.0), with a prior history of anti-resorptive therapy with bisphosphonates and denosumab. Teriparatide was started at an average of 8 (2-18) days post-fixation, with 20mcg daily for six months. Immediate full weight-bearing was permitted in three patients, while one was non-weight bearing for two months. The mean time to union was 12 (10 - 14) weeks. No side effects were observed over a mean follow-up of 58 (50 - 72) weeks. The use of teriparatide facilitated the quick union of AFF after surgical fixation. It appeared to be safe and promoted fracture healing in AFF.
  16. Braima KA, Sum JS, Ghazali AR, Muslimin M, Jeffery J, Lee WC, et al.
    PLoS One, 2013;8(10):e77924.
    PMID: 24194901 DOI: 10.1371/journal.pone.0077924
    BACKGROUND: The suburban transmission of malaria in Selangor, Malaysia's most developed and populous state still remains a concern for public health in this region. Despite much successful control efforts directed at its reduction, sporadic cases, mostly brought in by foreigners have continued to occur. In addition, cases of simian malaria caused by Plasmodium knowlesi, some with fatal outcome have caused grave concern to health workers. The aim of this study was to investigate the possibility of local malaria transmission in suburban regions of Selangor, which are adjacent to secondary rainforests.

    FINDINGS: A malaria survey spanning 7 years (2006 - 2012) was conducted in Selangor. A total of 1623 laboratory confirmed malaria cases were reported from Selangor's nine districts. While 72.6% of these cases (1178/1623) were attributed to imported malaria (cases originating from other countries), 25.5% (414/1623) were local cases and 1.9% (31/1623) were considered as relapse and unclassified cases combined. In this study, the most prevalent infection was P. vivax (1239 cases, prevalence 76.3%) followed by P. falciparum (211, 13.0%), P. knowlesi (75, 4.6%), P. malariae (71, 4.4%) and P. ovale (1, 0.06%). Mixed infections comprising of P. vivax and P. falciparum were confirmed (26, 1.6%). Entomological surveys targeting the residences of malaria patients' showed that the most commonly trapped Anopheles species was An. maculatus. No oocysts or sporozoites were found in the An. maculatus collected. Nevertheless, the possibility of An. maculatus being the malaria vector in the investigated locations was high due to its persistent occurrence in these areas.

    CONCLUSIONS: Malaria cases reported in this study were mostly imported cases. However the co-existence of local cases and potential Plasmodium spp. vectors should be cause for concern. The results of this survey reflect the need of maintaining closely monitored malaria control programs and continuous extensive malaria surveillance in Peninsula Malaysia.

  17. Lee WC, Chin PW, Lau YL, Chin LC, Fong MY, Yap CJ, et al.
    Malar J, 2013;12:88.
    PMID: 23496970 DOI: 10.1186/1475-2875-12-88
    Plasmodium knowlesi is a potentially life-threatening zoonotic malaria parasite due to its relatively short erythrocytic cycle. Microscopic identification of P. knowlesi is difficult, with "compacted parasite cytoplasm" being one of the important identifying keys. This report is about a case of hyperparasitaemic human P. knowlesi infection (27% parasitaemia) with atypical amoeboid morphology. A peninsular Malaysian was admitted to the hospital with malaria. He suffered anaemia and acute kidney function impairment. Microscopic examination, assisted by nested PCR and sequencing confirmed as P. knowlesi infection. With anti-malarial treatment and several medical interventions, patient survived and recovered. One-month medical follow-up was performed after recovery and no recrudescence was noted. This case report highlights the extreme hyperparasitaemic setting, the atypical morphology of P. knowlesi in the patient's erythrocytes, as well as the medical interventions involved in this successfully treated case.
  18. Lee WC, Wee L
    Malays Orthop J, 2019 Mar;13(1):42-44.
    PMID: 31001383 DOI: 10.5704/MOJ.1903.008
    We present a unique case of tibial post fracture of a posterior-stabilised total knee arthroplasty (PS-TKA) using highly crosslinked polyethylene (HXLPE) in the unafflicted limb of a patient who had poliomyelitis. The tibial post is an upright structure perpendicular to the PE insert articular surface which articulates with the cam of the femoral component to prevent excessive posterior translation of the tibia. We explore the choice of PS polyethylene (PE) inserts in patients with neuromuscular disorders (NMD). A 74-year old gentleman presented with recurrent knee pain seven years after the index PS-TKA with HXLPE. The TKA was performed on the unafflicted left limb (contralateral to the weak side affected by poliomyelitis). The posterior drawer test was positive. During the single-stage revision surgery, the HXLPE tibial post was noted to be broken. The liner was replaced with a thicker non-HXLPE. The patient achieved an excellent outcome at one-year post-surgery. This is the first report of HXLPE tibial post fracture in the unaffected knee of a patient with NMD affecting the lower limb. The HXLPE's reduced resistance to fatigue crack propagation might not be suitable in PS-TKA where there might be focal stress points on the tibial post, which was amplified in this case as it was the limb that the patient most depended on. When managing end-stage osteoarthritis with TKA in the unafflicted knee of a patient with NMD causing lower limb weakness, the selection of polyethylene material in PS-TKA may need more consideration than previously thought.
  19. Lee WC, Malleret B, Lau YL, Mauduit M, Fong MY, Cho JS, et al.
    Blood, 2014 May 01;123(18):e100-9.
    PMID: 24652986 DOI: 10.1182/blood-2013-12-541698
    Rosetting phenomenon has been linked to malaria pathogenesis. Although rosetting occurs in all causes of human malaria, most data on this subject has been derived from Plasmodium falciparum. Here, we investigate the function and factors affecting rosette formation in Plasmodium vivax. To achieve this, we used a range of novel ex vivo protocols to study fresh and cryopreserved P vivax (n = 135) and P falciparum (n = 77) isolates from Thailand. Rosetting is more common in vivax than falciparum malaria, both in terms of incidence in patient samples and percentage of infected erythrocytes forming rosettes. Rosetting to P vivax asexual and sexual stages was evident 20 hours postreticulocyte invasion, reaching a plateau after 30 hours. Host ABO blood group, reticulocyte count, and parasitemia were not correlated with P vivax rosetting. Importantly, mature erythrocytes (normocytes), rather than reticulocytes, preferentially form rosetting complexes, indicating that this process is unlikely to directly facilitate merozoite invasion. Although antibodies against host erythrocyte receptors CD235a and CD35 had no effect, Ag-binding fragment against the BRIC 4 region of CD236R significantly inhibited rosette formation. Rosetting assays using CD236R knockdown normocytes derived from hematopoietic stem cells further supports the role of glycophorin C as a receptor in P vivax rosette formation.
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