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A high incidence of serum IgG antibodies to the Epstein-Barr virus replication activator protein in nasopharyngeal carcinoma

Mathew A, Cheng HM, Sam CK, Joab I, Prasad U, Cochet C

Cancer Immunol Immunother, 1994 Jan;38(1):68-70.
PMID: 8299121

The BamHI Z EBV replication activator (ZEBRA) protein is involved in the switch from latency to productive cycle of Epstein-Barr virus. A recombinant ZEBRA protein was synthesized and assessed in enzyme-linked immunosorbent assay (ELISA) for serum IgG response in nasopharyngeal carcinoma (NPC) patients. In 100 NPC serum samples that were positive for IgA to the EBV viral capsid antigen (VCA), 75% had IgG anti-ZEBRA antibodies. In contrast, only 3/83 (3.6%) serum samples from healthy donors and 2/50 (4%) from other cancers were positive for IgG to ZEBRA. Interestingly, in a selected group of 100 NPC sera negative for IgA to VCA, 25% contained IgG anti-ZEBRA antibodies. This suggests that the ELISA for IgG anti-ZEBRA may also identify earlier cases of NPC not detected by the conventional immunofluorescence test for IgA to VCA.
Fulltext Alpha-tocotrienol is the most abundant tocotrienol isomer circulated in plasma and lipoproteins after postprandial tocotrienol-rich vitamin E supplementation

Fairus S, Nor RM, Cheng HM, Sundram K

Nutr J, 2012;11:5.
PMID: 22252050 DOI: 10.1186/1475-2891-11-5

Tocotrienols (T3) and tocopherols (T), both members of the natural vitamin E family have unique biological functions in humans. T3 are detected in circulating human plasma and lipoproteins, although at concentrations significantly lower than α-tocopherol (α-T). T3, especially α-T3 is known to be neuropotective at nanomolar concentrations and this study evaluated the postprandial fate of T3 and α-T in plasma and lipoproteins.
An investigation of aeroallergens affecting urban Malaysian asthmatics

Sam CK, Soon SC, Liam CK, Padmaja K, Cheng HM

Asian Pac J Allergy Immunol, 1998 Mar;16(1):17-20.
PMID: 9681124

We investigated the aeroallergens affecting 200 asthmatics from the University Hospital in Kuala Lumpur, Malaysia and found 164 (82%) patients with skin prick test (SPT) reactivity to one or more of a panel of 14 allergens, which included indoor and outdoor animal and plant aeroallergens. Reactivity was most frequent to the indoor airborne allergens, with 159 (79.5%) reacting to either or both house dust mite (Dermatophagoides) species and 87 (43.5%) to cockroach. The SPT reactivity to house dust mites corresponded with the finding that patients found house dust to be the main precipitant of asthmatic attacks.
Fulltext Angiotensin receptor neprilysin inhibitor as a novel antihypertensive drug: Evidence from Asia and around the globe

Lin DS, Wang TD, Buranakitjaroen P, Chen CH, Cheng HM, Chia YC, et al.

J Clin Hypertens (Greenwich), 2021 03;23(3):556-567.
PMID: 33305531 DOI: 10.1111/jch.14120

Hypertension is a worldwide epidemic that continues to grow, with a subset of patients responding poorly to current treatment available. This is especially relevant in Asia, which constitutes 61% of the global population. Hypertension in Asia is a unique entity that is often salt-sensitive, nocturnal, and systolic predominant. Sacubitril/valsartan is a first-in-class angiotensin receptor neprilysin inhibitor that was first used in heart failure with reduced ejection fraction. Sacubitril inhibits neprilysin, a metallopeptidase that degrades natriuretic peptides (NPs). NPs exert sympatholytic, diuretic, natriuretic, vasodilatory, and insulin-sensitizing effects mostly via cyclic guanosine monophosphate (cGMP)-mediated pathways. As an antihypertensive agent, sacubitril/valsartan has outperformed angiotensin II receptor type 1 blockers (ARBs), with additional reductions of office systolic blood pressures ranging between 5 and 7 mmHg, in multiple studies in Asia and around the globe. The drug was well tolerated even in the elderly or those with chronic kidney disease. Its mechanisms of actions are particularly attractive for treatment of hypertension in Asia. Sacubitril/valsartan offers a novel, dual class, single-molecule property that may be considered as first-line antihypertensive therapy. Further investigations are needed to validate its safety for long-term use and to explore other potentials such as in the management of insulin resistance and obesity, which often coexist with hypertension in Asia.
Anti-phospholipid antibody isotypes in normal human sera

Cheng HM, Wong KK

Immunol Lett, 1990 Jan;23(3):183-6.
PMID: 2307490

Heat-sensitive serum masking cofactor(s) of antiphospholipid antibody (aPL) in normal human sera (NHS) are specifically inactivated at 56 degrees C. The degree of binding in ELISA by unmasked aPL in NHS was equivalent to that in non-heated, aPL-reactive autoimmune SLE sera. Previously "negative" SLE sera also reacted equally strongly in the aPL ELISA when similarly heat-inactivated. Isotype studies by ELISA of the heat-potentiated aPL in 36 NHS revealed the presence of specific IgG (34/36), IgM (11/36) and IgA (24/36) aPL antibodies. 11/36 (31%) NHS had all three aPL isotypes while 13/36 (36%) had both IgG and IgA antibodies to phospholipid.
Anticoagulant activity of heat-unmasked antiphospholipid autoantibody in normal human plasma?

Ismail R, Cheng HM

Thromb Res, 1994 Jan 15;73(2):143-7.
PMID: 8171414 DOI: 10.1016/0049-3848(94)90090-6
Fulltext Antioxidant and cytotoxic activities of three species of tropical seaweeds

Chia YY, Kanthimathi MS, Khoo KS, Rajarajeswaran J, Cheng HM, Yap WS

BMC Complement Altern Med, 2015;15:339.
PMID: 26415532 DOI: 10.1186/s12906-015-0867-1

Three species of seaweeds (Padina tetrastromatica, Caulerpa racemosa and Turbinaria ornata) are widely consumed by Asians as nutraceutical food due to their antioxidant properties. Studies have shown that these seaweeds exhibit bioactivities which include antimicrobial, antiviral, anti-hypertensive and anticoagulant activities. However, investigations into the mechanisms of action pertaining to the cytotoxic activity of the seaweeds are limited. The aim of this study was to determine the antioxidant and cytotoxic activities of whole extracts of P. tetrastromatica, C. racemosa and T. ornata, including the cellular events leading to the apoptotic cell death of the extract treated-MCF-7 cells. Bioassay guided fractionation was carried out and the compounds identified.
Antioxidant status following postprandial challenge of two different doses of tocopherols and tocotrienols

Fairus S, Cheng HM, Sundram K

J Integr Med, 2020 Jan;18(1):68-79.
PMID: 31812339 DOI: 10.1016/j.joim.2019.11.005

OBJECTIVE: Tocotrienols (T3s) have been hypothesized to have greater antioxidant capacity than tocopherols (Ts) due to differences in biokinetics that affect their absorption and function. The present trial compares the antioxidant effectiveness following postprandial challenge of two different doses of α-T or palm T3-rich fraction (TRF) treatments and evaluates their dose-response effects on antioxidant status.
METHODS: Ten healthy volunteers were given four different doses of vitamin E formulations (268 mg α-T, 537 mg α-T, 263 mg TRF or 526 mg TRF) in a cross-over postprandial trial. Blood was sampled at 0, 2, 4, 5, 6 and 8 hours after meal consumption and plasma antioxidant status including total glutathione, superoxide dismutase, malondialdehyde (MDA), ferric reducing antioxidant potential and trolox-equivalent antioxidant capacity, was analyzed.
RESULTS: Supplementation with the different doses of either α-T or TRF did not significantly improve overall antioxidant status. There was no significant difference in overall antioxidant status among treatments at the different doses compared. However, a significant dose-response effect was observed for plasma MDA throughout the 8-hour postprandial period. MDA was significantly lower after the 537 mg α-T treatment, compared to the 268 mg α-T treatment; it was also lower after the 526 mg TRF treatment compared to the 263 mg TRF treatment (P
Fulltext Antiphospholipid antibodies and stroke in the young--a study of three cases

Lee MK, Cheng HM, Ng SC, Menaka N, Tan CT, Wang F

Med J Malaysia, 1993 Sep;48(3):330-5.
PMID: 8183147

Cerebral infarction in the young is likely to be non-atheromatous. While in previous studies no cause has been found in 40% to 50% of patients, an increasing role for haemorheological factors is becoming apparent. Among these, an association between antiphospholipid antibodies (aPLs) and ischaemic cerebrovascular disease is now well-recognised. This entity has not been previously reported in Malaysian patients. In a study of 80 patients with stroke below the age of 50 years who were seen at the University Hospital, Kuala Lumpur, between January 1982 and May 1992, 3 patients with ischaemic cerebral infarction were found to have aPLs. aPLs was detected using ELISA method for anticardiolipin antibodies (aCLs), and presence of lupus anticoagulant (LA) was established by kaolin clotting time, thromboplastin inhibition test and platelet neutralisation procedure. Only 1 patient had active systemic lupus erythematous. Cerebrovascular events were recurrent in one of the 2 non-lupus patients. aPL-related stroke should be considered in young patients who have cerebral ischaemia occurring without obvious cause. More cases are likely to emerge in Malaysia with active screening.
Fulltext Applications of artificial intelligence for hypertension management

Tsoi K, Yiu K, Lee H, Cheng HM, Wang TD, Tay JC, et al.

J Clin Hypertens (Greenwich), 2021 03;23(3):568-574.
PMID: 33533536 DOI: 10.1111/jch.14180

The prevalence of hypertension is increasing along with an aging population, causing millions of premature deaths annually worldwide. Low awareness of blood pressure (BP) elevation and suboptimal hypertension diagnosis serve as the major hurdles in effective hypertension management. The advent of artificial intelligence (AI), however, sheds the light of new strategies for hypertension management, such as remote supports from telemedicine and big data-derived prediction. There is considerable evidence demonstrating the feasibility of AI applications in hypertension management. A foreseeable trend was observed in integrating BP measurements with various wearable sensors and smartphones, so as to permit continuous and convenient monitoring. In the meantime, further investigations are advised to validate the novel prediction and prognostic tools. These revolutionary developments have made a stride toward the future model for digital management of chronic diseases.
Fulltext Assessment of antioxidant capacity and cytotoxicity of selected Malaysian plants

Ling LT, Radhakrishnan AK, Subramaniam T, Cheng HM, Palanisamy UD

Molecules, 2010 Apr;15(4):2139-51.
PMID: 20428033 DOI: 10.3390/molecules15042139

Thirteen Malaysian plants; Artocarpus champeden, Azadirachta indica, Fragaria x ananassa, Garcinia mangostana, Lawsonia inermis, Mangifera indica, Nephelium lappaceum, Nephelium mutobile, Peltophorum pterocarpum, Psidium guajava and Syzygium aqueum, selected for their use in traditional medicine, were subjected to a variety of assays. Antioxidant capability, total phenolic content, elemental composition, as well as it cytotoxity to several cell lines of the aqueous and ethanolic extracts from different parts of these selected Malaysian plants were determined. In general, the ethanolic extracts were better free radical scavengers than the aqueous extracts and some of the tested extracts were even more potent than a commercial grape seed preparation. Similar results were seen in the lipid peroxidation inhibition studies. Our findings also showed a strong correlation of antioxidant activity with the total phenolic content. These extracts when tested for its heavy metals content, were found to be below permissible value for nutraceutical application. In addition, most of the extracts were found not cytotoxic to 3T3 and 4T1 cells at concentrations as high as 100 microg/mL. We conclude that although traditionally these plants are used in the aqueous form, its commercial preparation could be achieved using ethanol since a high total phenolic content and antioxidant activity is associated with this method of preparation.
Bacterial immunity and immunogenesis of normal human salivary IgA and serum IgG2 antiphospholipid autoantibody: a link?

Cheng HM, Sam CK

Immunol Lett, 1990 Oct;26(1):7-10.
PMID: 2276764

The anti-phospholipid antibody (aPL) in 26 heat-inactivated normal human sera (NHS) was tested for IgG subclass in ELISA. The specific antibody in NHS included all four IgG antibody subclasses, as well as IgA. The incidence of IgG subclasses ranged from 50% (13/26) for IgG1 to 92% (24/26) for IgG2. Specific IgA anti-phospholipid antibody (aPL) was detected by ELISA in 38% (28/73) of normal human saliva. The salivary IgA aPL bound preferentially to anionic phospholipids including cardiolipin, phosphatidylserine and phosphatidic acid but not to phosphatidylcholine or sphingomyelin. Unlike aPL in normal human sera, aPL in saliva was predominantly not associated with the previously described heat-labile inhibitor of aPL. This may indicate a role of salivary IgA aPL in local immunity by binding to cross-reactive bacterial cell surface components including phospholipids.
Fulltext Cardiovascular risk assessment tools in Asia

Zhang Y, Miao H, Chia YC, Buranakitjaroen P, Siddique S, Shin J, et al.

J Clin Hypertens (Greenwich), 2022 Jan 04.
PMID: 34981620 DOI: 10.1111/jch.14336

Cardiovascular disease (CVD) is becoming the most important burden to health care systems in most part of the world, especially in Asia. Aiming at identifying high risk individuals and tailoring preventive treatment, many cardiovascular risk assessment tools have been established and most of them were developed in Western countries. However, these cardiovascular risk assessment tools cannot be used interchangeably without recalibration because of the different risk factor profiles (ie, greater absolute burden of hypertension and lower level of total-cholesterol in Asians and higher prevalence of metabolic disorders in South Asians) and different CVD profiles (higher ratio of stroke/coronary heart disease in Asians) between Western and Asian populations. Original risk models such as Prediction for ASCVD Risk in China (China-PAR) and Japan Arteriosclerosis Longitudinal Study (JALS) score have been developed and well validated for specific countries, while most of countries/regions in Asia are using established models. Due to higher incidence of stroke in Asians, risk factors like hypertension should weigh more in cardiovascular risk assessment comparing with Western populations, but their actual proportions should be based on CVD profiles in specific countries/regions. The authors encourage the development of new cardiovascular risk assessment tools for Asians, if possible. Still, modifying established models with native epidemiological data of risk factor as well as CVD is acceptable in regions where health care resources are insufficient.
Fulltext Central blood pressure for the management of hypertension: Is it a practical clinical tool in current practice?

Cheng HM, Chuang SY, Wang TD, Kario K, Buranakitjaroen P, Chia YC, et al.

J Clin Hypertens (Greenwich), 2020 03;22(3):391-406.
PMID: 31841279 DOI: 10.1111/jch.13758

Since noninvasive central blood pressure (BP) measuring devices are readily available, central BP has gained growing attention regarding its clinical application in the management of hypertension. The disagreement between central and peripheral BP has long been recognized. Some previous studies showed that noninvasive central BP may be better than the conventional brachial BP in association with target organ damages and long-term cardiovascular outcomes. Recent studies further suggest that the central BP strategy for confirming a diagnosis of hypertension may be more cost-effective than the conventional strategy, and guidance of hypertension management with central BP may result in less use of medications to achieve BP control. Despite the use of central BP being promising, more randomized controlled studies comparing central BP-guided therapeutic strategies with conventional care for cardiovascular events reduction are required because noninvasive central and brachial BP measures are conveniently available. In this brief review, the rationale supporting the utility of central BP in clinical practice and relating challenges are summarized.
Fulltext Characteristics and control of the 24-hour ambulatory blood pressure in patients with metabolic syndrome

Huang JF, Li Y, Shin J, Chia YC, Sukonthasarn A, Turana Y, et al.

J Clin Hypertens (Greenwich), 2021 03;23(3):450-456.
PMID: 33629806 DOI: 10.1111/jch.14229

Asian countries are facing an increasing prevalence of metabolic syndrome (MetS), which may aggravate the burden of cardiovascular diseases in this region. MetS is closely associated with ambulatory blood pressure (BP). Patients with MetS, compared to those without, had a twofold higher risk of new-onset office, home, or ambulatory hypertension. Furthermore, the risk of new-onset MetS in patients with white-coat, masked and sustained hypertension was also doubled compared to normotensives. High-risk masked hypertension and blunted nighttime BP dipping are common in patients with MetS, suggesting perfect 24-hour BP control with long-acting antihypertensive drugs and early initiation of combination therapy might be especially important for patients with MetS.
Fulltext Characteristics of hypertension in obstructive sleep apnea: An Asian experience

Hoshide S, Kario K, Chia YC, Siddique S, Buranakitjaroen P, Tsoi K, et al.

J Clin Hypertens (Greenwich), 2021 03;23(3):489-495.
PMID: 33705599 DOI: 10.1111/jch.14184

Obstructive sleep apnea (OSA) is a risk of hypertension and is associated with cardiovascular disease (CVD) incidence. In Asian countries, the prevalence of OSA is high, as in Western countries. When blood pressure (BP) is evaluated in OSA individuals using ambulatory BP monitoring (ABPM), the BP phenotype often indicates abnormal BP variability, such as increased nighttime BP or abnormal diurnal BP variation, that is, non-dipper pattern, riser pattern, and morning BP surge, and all these conditions have been associated with increased CVD events. Asians have a higher prevalence of increased nighttime BP or morning BP surge than Westerners. Therefore, this review paper focused on OSA and hypertension from an Asian perspective to investigate the importance of the association between OSA and hypertension in the Asian population. Such abnormal BP variability has been shown to be associated with progression of arterial stiffness, and this association could provoke a vicious cycle between abnormal BP phenotypes and arterial stiffness, a phenomenon recognized as systemic hemodynamic atherothrombotic syndrome (SHATS). OSA may be one of the background factors that augment SHATS. An oxygen-triggered nocturnal oscillometric BP measurement device combined with a pulse oximeter for continuous SpO2 monitoring could detect BP variability caused by OSA. In addition to treating the OSA, accurate and reliable detection and treatment of any residual BP elevation and BP variability caused by OSA would be necessary to prevent CVD events. However, more detailed detection of BP variability, such as beat-by-beat BP monitoring, would further help to reduce CV events.
Fulltext Clinical significance of nocturnal home blood pressure monitoring and nocturnal hypertension in Asia

Fujiwara T, Hoshide S, Tomitani N, Cheng HM, Soenarta AA, Turana Y, et al.

J Clin Hypertens (Greenwich), 2021 03;23(3):457-466.
PMID: 33591641 DOI: 10.1111/jch.14218

Nocturnal home blood pressure (BP) monitoring has been used in clinical practice for ~20 years. The authors recently showed that nocturnal systolic BP (SBP) measured by a home BP monitoring (HBPM) device in a Japanese general practice population was a significant predictor of incident cardiovascular disease (CVD) events, independent of office and morning home SBP levels, and that masked nocturnal hypertension obtained by HBPM (defined as nocturnal home BP ≥ 120/70 mmHg and average morning and evening BP
Fulltext Comparison of guidelines for the management of hypertension: Similarities and differences between international and Asian countries; perspectives from HOPE-Asia Network

Chia YC, Turana Y, Sukonthasarn A, Zhang Y, Shin J, Cheng HM, et al.

J Clin Hypertens (Greenwich), 2021 03;23(3):422-434.
PMID: 33634570 DOI: 10.1111/jch.14226

Guidelines on the management of hypertension have been developed by various professional bodies and institutions to primarily address the issues of diagnosis, treatment, and control in order to rationalize and improve the management of hypertension. Hypertension guidelines across the world have recently been updated following the new and controversial lower blood pressure threshold of ≥130/80 mmHg for the diagnosis of hypertension adopted by the Americans. While there are differences between the major as well as between the Asian national guidelines, there were also many similarities. This paper discusses and highlights the differences and similarities between the major international guidelines of the American College of Cardiology/American Heart Association, of the European Society of Cardiology/European Society of Hypertension, and of the International Society of Hypertension and also compares them with the Asian guidelines.
Cryptic antiphospholipid autoantibodies and serum co-inhibitors

Cheng HM

Autoimmunity, 1994;19(2):127-33.
PMID: 7772702 DOI: 10.3109/08916939409009540
Cryptic natural autoantibodies and co-potentiators

Cheng HM, Chamley L

Autoimmun Rev, 2008 Jun;7(6):431-4.
PMID: 18558357 DOI: 10.1016/j.autrev.2008.03.011

Natural autoantibodies are normal components of the humoral arm of the immune system found in clinically healthy individuals. There are two subpopulations of natural antibodies, including an overt group of antibodies that are readily detected in unfractionated normal human sera. The other natural antibody subgroup is revealed by physico or biochemical treatment of normal human sera in vitro. Unmasking of this latter cryptic natural autoantibodies (cNA) may occur in vivo by local factors in the tissue environment of disease states. The masking cryptic factors may be immunoglobulin (Ig) or non-Ig in nature. These factors may either be co-inhibitors or co-enhancers of cNA. In the heat-potentiated binding of natural anti-phospholipid antibodies, apolipoprotein H (beta 2-glycoprotein I) appears to act as a co-enhancer. The immuno-relationship between the in vitro and in vivo cNA phenomenon remains to be elucidated.

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