Displaying publications 401 - 420 of 522 in total

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  1. Endogenous and induced angiogenic characteristics of human chorion-derived stem cells
    Nur Fariha MM, Chua KH, Tan GC, Lim YH, Hayati AR
    Cell Biol Int, 2012;36(12):1145-53.
    PMID: 22957758 DOI: 10.1042/CBI20120044
    Cell-based therapy using stem cells has emerged as one of the pro-angiogenic methods to enhance blood vessel growth and sprouting in ischaemic conditions. This study investigated the endogenous and induced angiogenic characteristics of hCDSC (human chorion-derived stem cell) using QPCR (quantitative PCR) method, immunocytochemistry and fibrin-matrigel migration assay. The results showed that cultured hCDSC endogenously expressed angiogenic-endogenic-associated genes (VEGF, bFGF, PGF, HGF, Ang-1, PECAM-1, eNOS, Ve-cad, CD34, VEGFR-2 and vWF), with significant increase in mRNA levels of PGF, HGF, Ang-1, eNOS, VEGFR-2 and vWF following induction by bFGF (basic fibroblast growth factor) and VEGF (vascular endothelial growth factor). These enhanced angiogenic properties suggest that induced hCDSC provides a stronger angiogenic effect for the treatment of ischaemia. After angiogenic induction, hCDSC showed no reduction in the expression of the stemness genes, but had significantly higher levels of mRNA of Oct-4, Nanog (3), FZD9, ABCG-2 and BST-1. The induced cells were positive for PECAM-1 (platelet/endothelial cell adhesion molecule 1) and vWF (von Willebrand factor) with immunocytochemistry staining. hCDSC also showed endothelial migration behaviour when cultured in fibrin-matrigel construct and were capable of forming vessels in vivo after implanting into nude mice. These data suggest that hCDSC could be the cells of choice in the cell-based therapy for pro-angiogenic purpose.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/analysis; Intercellular Signaling Peptides and Proteins/genetics*
  2. Fulltext Role of Delta-like 4 in Jagged1-induced tumour angiogenesis and tumour growth
    Oon CE, Bridges E, Sheldon H, Sainson RCA, Jubb A, Turley H, et al.
    Oncotarget, 2017 Jun 20;8(25):40115-40131.
    PMID: 28445154 DOI: 10.18632/oncotarget.16969
    Delta-like 4 (DLL4) and Jagged1 (JAG1) are two key Notch ligands implicated in tumour angiogenesis. They were shown to have opposite effects on mouse retinal and adult regenerative angiogenesis. In tumours, both ligands are upregulated but their relative effects and interactions in tumour biology, particularly in tumour response to therapeutic intervention are unclear. Here we demonstrate that DLL4 and JAG1 displayed equal potency in stimulating Notch target genes in HMEC-1 endothelial cells but had opposing effects on sprouting angiogenesis in vitro. Mouse DLL4 or JAG1 expressed in glioblastoma cells decreased tumour cell proliferation in vitro but promoted tumour growth in vivo. mDLL4-expressing tumours showed fewer but larger vessels whereas mJAG1-tumours produced more vessels. In both tumour types pericyte coverage was decreased but the vessels were more perfused. Both ligands increased tumour resistance towards anti-VEGF therapy but the resistance was higher in mDLL4-tumours versus mJAG1-tumours. However, their sensitivity to the therapy was restored by blocking Notch signalling with dibenzazepine. Importantly, anti-DLL4 antibody blocked the effect of JAG1 on tumour growth and increased vessel branching in vivo. The mechanism behind the differential responsiveness was due to a positive feedback loop for DLL4-Notch signalling, rendering DLL4 more dominant in activating Notch signalling in the tumour microenvironment. We concluded that DLL4 and JAG1 promote tumour growth by modulating tumour angiogenesis via different mechanisms. JAG1 is not antagonistic but utilises DLL4 in tumour angiogenesis. The results suggest that anti-JAG1 therapy should be explored in conjunction with anti-DLL4 treatment in developing anti-Notch therapies in clinics.
    Matched MeSH terms: Intracellular Signaling Peptides and Proteins/genetics; Intracellular Signaling Peptides and Proteins/metabolism*
  3. Fulltext Antimicrobial activities of Bacillus velezensis strains isolated from stingless bee products against methicillin-resistant Staphylococcus aureus
    Baharudin MMA, Ngalimat MS, Mohd Shariff F, Balia Yusof ZN, Karim M, Baharum SN, et al.
    PLoS One, 2021;16(5):e0251514.
    PMID: 33974665 DOI: 10.1371/journal.pone.0251514
    Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) have reached epidemic proportions globally. Therefore, there is an urgent need for a continuous supply of antibiotics to combat the problem. In this study, bacteria initially identified as species belonging to the Bacillus amyloliquefaciens operational group were re-identified based on the housekeeping gene, gyrB. Cell-free supernatants (CFS) from the strains were used for antimicrobial tests using the agar well diffusion assay against MRSA and various types of pathogenic bacteria. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and physicochemical characteristics of the CFS were determined. Based on gyrB sequence analysis, five strains (PD9, B7, PU1, BP1 and L9) were identified as Bacillus velezensis. The CFS of all B. velezensis strains showed broad inhibitory activities against Gram-negative and -positive as well as MRSA strains. Strain PD9 against MRSA ATCC 33742 was chosen for further analysis as it showed the biggest zone of inhibition (21.0 ± 0.4 mm). The MIC and MBC values obtained were 125 μl/ml. The crude antimicrobial extract showed bactericidal activity and was stable at various temperatures (40-80°C), pH (4-12), surfactants (Tween 20, Tween 80, SDS and Triton X-100) and metal ions (MgCI2, NaCI2, ZnNO3 and CuSO4) when tested. However, the crude extract was not stable when treated with proteinase K. All these properties resembled the characteristics of peptides. The antimicrobial compound from the selected strain was purified by using solvent extraction method and silica gel column chromatography. The purified compound was subjected to High Performance Liquid Chromatography which resulted in a single peak of the anti-MRSA compound being detected. The molecular weight of the anti-MRSA compound was determined by using SDS-PAGE and zymogram. The size of the purified antimicrobial peptide was approximately ~ 5 kDa. The antimicrobial peptide produced from B. velezensis strain PD9 is a promising alternative to combat the spread of MRSA infections in the future.
    Matched MeSH terms: Antimicrobial Cationic Peptides/isolation & purification*; Antimicrobial Cationic Peptides/pharmacology
  4. Squamous odontogenic tumor of the mandible: a case report demonstrating immunoexpression of Notch1, 3, 4, Jagged1 and Delta1
    Siar CH, Nakano K, Ng KH, Tomida M, Nagatsuka H, Kawakami T
    Eur J Med Res, 2010 Apr 08;15(4):180-4.
    PMID: 20554499
    BACKGROUND: Squamous odontogenic tumor (SOT) is a rare benign odontogenic epithelial neoplasm. A slow-growing painless expansive swelling is the common presenting symptom. Histopathologically, SOT can be easily misdiagnosed as an acanthomatous ameloblastoma. Although Notch receptors and ligands have been shown to play a role in cell fate decisions in ameloblastomas, the role of these cell signaling molecules in SOT is unknown.

    CASE REPORT: This paper describes a case of SOT affecting the anterior mandible of a 10-year-old Indian female. The patient was treated by local surgical excision and there has been no follow-up clinical record of recurrence 5 years after primary treatment. Histo?pathological examination revealed a solid, locally-infiltrative neoplasm composed of bland-looking squamatoid islands scattered in a mature fibrous connective tissue stroma and the diagnosis was SOT. Immunohistochemical evaluation showed positive reactivity of varying intensity in the neoplastic epithelial cells for Notch1, Notch3, Notch4, and their ligands Jagged1 and Delta1. Expression patterns showed considerable overlap. No immunoreactivity was detected for Notch2 and Jagged2.

    CONCLUSIONS: Present findings suggest that Notch receptors and their ligands play differential roles in the cytodifferentiation of SOT.

    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism*; Intracellular Signaling Peptides and Proteins
  5. A critical role of TRPM2 channel in Aβ42 -induced microglial activation and generation of tumor necrosis factor-α
    Alawieyah Syed Mortadza S, Sim JA, Neubrand VE, Jiang LH
    Glia, 2018 03;66(3):562-575.
    PMID: 29143372 DOI: 10.1002/glia.23265
    Amyloid β (Aβ)-induced neuroinflammation plays an important part in Alzheimer's disease (AD). Emerging evidence supports a role for the transient receptor potential melastatin-related 2 (TRPM2) channel in Aβ-induced neuroinflammation, but how Aβ induces TRPM2 channel activation and this relates to neuroinflammation remained poorly understood. We investigated the mechanisms by which Aβ42 activates the TRPM2 channel in microglial cells and the relationships to microglial activation and generation of tumor necrosis factor-α (TNF-α), a key cytokine implicated in AD. Exposure to 10-300 nM Aβ42 induced concentration-dependent microglial activation and generation of TNF-α that were ablated by genetically deleting (TRPM2 knockout ;TRPM2-KO) or pharmacologically inhibiting the TRPM2 channel, revealing a critical role of this channel in Aβ42 -induced microglial activation and generation of TNF-α. Mechanistically, Aβ42 activated the TRPM2 channel via stimulating generation of reactive oxygen species (ROS) and activation of poly(ADPR) polymerase-1 (PARP-1). Aβ42 -induced generation of ROS and activation of PARP-1 and TRPM2 channel were suppressed by inhibiting protein kinase C (PKC) and NADPH oxidases (NOX). Aβ42 -induced activation of PARP-1 and TRPM2 channel was also reduced by inhibiting PYK2 and MEK/ERK. Aβ42 -induced activation of PARP-1 was attenuated by TRPM2-KO and moreover, the remaining PARP-1 activity was eliminated by inhibiting PKC and NOX, but not PYK2 and MEK/ERK. Collectively, our results suggest that PKC/NOX-mediated generation of ROS and subsequent activation of PARP-1 play a role in Aβ42 -induced TRPM2 channel activation and TRPM2-dependent activation of the PYK2/MEK/ERK signalling pathway acts as a positive feedback to further facilitate activation of PARP-1 and TRPM2 channel. These findings provide novel insights into the mechanisms underlying Aβ-induced AD-related neuroinflammation.
    Matched MeSH terms: Amyloid beta-Peptides/administration & dosage; Amyloid beta-Peptides/metabolism*
  6. Fulltext Pluripotent Human embryonic stem cell derived neural lineages for in vitro modelling of enterovirus 71 infection and therapy
    Yap MS, Tang YQ, Yeo Y, Lim WL, Lim LW, Tan KO, et al.
    Virol J, 2016 Jan 06;13:5.
    PMID: 26738773 DOI: 10.1186/s12985-015-0454-6
    The incidence of neurological complications and fatalities associated with Hand, Foot & Mouth disease has increased over recent years, due to emergence of newly-evolved strains of Enterovirus 71 (EV71). In the search for new antiviral therapeutics against EV71, accurate and sensitive in vitro cellular models for preliminary studies of EV71 pathogenesis is an essential prerequisite, before progressing to expensive and time-consuming live animal studies and clinical trials.
    Matched MeSH terms: Peptides/pharmacology
  7. Fulltext Identification of protein markers in patients infected with Plasmodium knowlesi, Plasmodium falciparum and Plasmodium vivax
    Mu AK, Bee PC, Lau YL, Chen Y
    Int J Mol Sci, 2014;15(11):19952-61.
    PMID: 25372941 DOI: 10.3390/ijms151119952
    Malaria is caused by parasitic protozoans of the genus Plasmodium and is one of the most prevalent infectious diseases in tropical and subtropical regions. For this reason, effective and practical diagnostic methods are urgently needed to control the spread of malaria. The aim of the current study was to identify a panel of new malarial markers, which could be used to diagnose patients infected with various Plasmodium species, including P. knowlesi, P. vivax and P. falciparum. Sera from malaria-infected patients were pooled and compared to control sera obtained from healthy individuals using the isobaric tags for relative and absolute quantitation (iTRAQ) technique. Mass spectrometry was used to identify serum proteins and quantify their relative abundance. We found that the levels of several proteins were increased in pooled serum from infected patients, including cell adhesion molecule-4 and C-reactive protein. In contrast, the serum concentration of haptoglobin was reduced in malaria-infected individuals, which we verified by western blot assay. Therefore, these proteins might represent infectious markers of malaria, which could be used to develop novel diagnostic tools for detecting P. knowlesi, P. vivax and P. falciparum. However, these potential malarial markers will need to be validated in a larger population of infected individuals.
    Matched MeSH terms: Peptides/metabolism
  8. Fulltext IGF-1 enhances cell proliferation and survival during early differentiation of mesenchymal stem cells to neural progenitor-like cells
    Huat TJ, Khan AA, Pati S, Mustafa Z, Abdullah JM, Jaafar H
    BMC Neurosci, 2014;15:91.
    PMID: 25047045 DOI: 10.1186/1471-2202-15-91
    There has been increasing interest recently in the plasticity of mesenchymal stem cells (MSCs) and their potential to differentiate into neural lineages. To unravel the roles and effects of different growth factors in the differentiation of MSCs into neural lineages, we have differentiated MSCs into neural lineages using different combinations of growth factors. Based on previous studies of the roles of insulin-like growth factor 1 (IGF-1) in neural stem cell isolation in the laboratory, we hypothesized that IGF-1 can enhance proliferation and reduce apoptosis in neural progenitor-like cells (NPCs) during differentiation of MSCs into NCPs.We induced MSCs differentiation under four different combinations of growth factors: (A) EGF + bFGF, (B) EGF + bFGF + IGF-1, (C) EGF + bFGF + LIF, (D) EGF + bFGF + BDNF, and (E) without growth factors, as a negative control. The neurospheres formed were characterized by immunofluorescence staining against nestin, and the expression was measured by flow cytometry. Cell proliferation and apoptosis were also studied by MTS and Annexin V assay, respectively, at three different time intervals (24 hr, 3 days, and 5 days). The neurospheres formed in the four groups were then terminally differentiated into neuron and glial cells.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism
  9. Fulltext Effects of annatto-derived tocotrienol supplementation on osteoporosis induced by testosterone deficiency in rats
    Chin KY, Ima-Nirwana S
    Clin Interv Aging, 2014;9:1247-59.
    PMID: 25120355 DOI: 10.2147/CIA.S67016
    BACKGROUND: Previous animal models have demonstrated that tocotrienol is a potential treatment for postmenopausal osteoporosis. This study evaluated the antiosteoporotic effects of annatto-derived tocotrienol (AnTT) using a testosterone-deficient osteoporotic rat model.
    METHODS: Forty rats were divided randomly into baseline, sham, orchidectomized, AnTT, and testosterone groups. The baseline group was euthanized without undergoing any surgical treatment or intervention. The remaining groups underwent orchidectomy, with the exception of the sham group. AnTT 60 mg/kg/day was given orally to the AnTT group, while the testosterone group received testosterone enanthate 7 mg/kg per week intramuscularly for 8 weeks. Structural changes in trabecular bone at the proximal tibia were examined using microcomputed tomography. Structural and dynamic changes at the distal femur were examined using histomorphometric methods. Serum osteocalcin and C-terminal of type 1 collagen crosslinks were measured. Bone-related gene expression in the distal femur was examined.
    RESULTS: There were significant degenerative changes in structural indices in the orchidectomized group (P<0.05), but no significant changes in dynamic indices, bone remodeling markers, or gene expression (P>0.05) when compared with the sham group. The AnTT group showed significant improvement in structural indices at the femur (P<0.05) and significantly increased expression of bone formation genes (P<0.05). Testosterone was more effective than AnTT in preventing degeneration of bone structural indices in the femur and tibia (P<0.05).
    CONCLUSION: AnTT supplementation improves bone health in testosterone-deficient rats by enhancing bone formation. Its potential should be evaluated further by varying the dosage and treatment duration.
    KEYWORDS: bone remodeling; osteoporosis; testosterone; tocotrienol
    Matched MeSH terms: Peptides/blood
  10. Synthesis of α, β-unsaturated carbonyl based compounds as acetylcholinesterase and butyrylcholinesterase inhibitors: characterization, molecular modeling, QSAR studies and effect against amyloid β-induced cytotoxicity
    Bukhari SN, Jantan I, Masand VH, Mahajan DT, Sher M, Naeem-ul-Hassan M, et al.
    Eur J Med Chem, 2014 Aug 18;83:355-65.
    PMID: 24980117 DOI: 10.1016/j.ejmech.2014.06.034
    A series of novel carbonyl compounds was synthesized by a simple, eco-friendly and efficient method. These compounds were screened for anti-oxidant activity, in vitro cytotoxicity and for inhibitory activity for acetylcholinesterase and butyrylcholinesterase. The effect of these compounds against amyloid β-induced cytotoxicity was also investigated. Among them, compound 14 exhibited strong free radical scavenging activity (18.39 μM) while six compounds (1, 3, 4, 13, 14, and 19) were found to be the most protective against Aβ-induced neuronal cell death in PC12 cells. Compounds 4 and 14, containing N-methyl-4-piperidone linker, showed high acetylcholinesterase inhibitory activity as compared to reference drug donepezil. Molecular docking and QSAR (Quantitative Structure-Activity Relationship) studies were also carried out to determine the structural features that are responsible for the acetylcholinesterase and butyrylcholinesterase inhibitory activity.
    Matched MeSH terms: Amyloid beta-Peptides/toxicity*
  11. Thymoquinone prevents β-amyloid neurotoxicity in primary cultured cerebellar granule neurons
    Ismail N, Ismail M, Mazlan M, Latiff LA, Imam MU, Iqbal S, et al.
    Cell Mol Neurobiol, 2013 Nov;33(8):1159-69.
    PMID: 24101432 DOI: 10.1007/s10571-013-9982-z
    Thymoquinone (TQ), a bioactive constituent of Nigella sativa Linn (N. sativa) has demonstrated several neuropharmacological attributes. In the present study, the neuroprotective properties of TQ were investigated by studying its anti-apoptotic potential to diminish β-amyloid peptide 1-40 sequence (Aβ1-40)-induced neuronal cell death in primary cultured cerebellar granule neurons (CGNs). The effects of TQ against Aβ1-40-induced neurotoxicity, morphological damages, DNA condensation, the generation of reactive oxygen species, and caspase-3, -8, and -9 activation were investigated. Pretreatment of CGNs with TQ (0.1 and 1 μM) and subsequent exposure to 10 μM Aβ1-40 protected the CGNs against the neurotoxic effects of the latter. In addition, the CGNs were better preserved with intact cell bodies, extensive neurite networks, a loss of condensed chromatin and less free radical generation than those exposed to Aβ1-40 alone. TQ pretreatment inhibited Aβ1-40-induced apoptosis of CGNs via both extrinsic and intrinsic caspase pathways. Thus, the findings of this study suggest that TQ may prevent neurotoxicity and Aβ1-40-induced apoptosis. TQ is, therefore, worth studying further for its potential to reduce the risks of developing Alzheimer's disease.
    Matched MeSH terms: Amyloid beta-Peptides/toxicity*
  12. Genetic polymorphisms of TP53-binding protein 1 (TP53BP1) gene and association with breast cancer risk
    Naidu R, Har YC, Taib NA
    APMIS, 2011 Jul;119(7):460-7.
    PMID: 21635553 DOI: 10.1111/j.1600-0463.2011.02753.x
    In the present study, we evaluated the association between the TP53BP1 Glu353Asp and T-885G polymorphisms and breast cancer risk as well as with the clinicopathological characteristics of the patients. Genotyping of these polymorphisms was performed on 387 breast cancer patients and 252 normal and healthy women who had no history of any malignancy using PCR-RFLP method in a hospital-based Malaysian population. Breast cancer risk was not observed among women who were heterozygous (OR(adj) = 0.887; 95% CI, 0.632-1.245) or homozygous (OR(adj) = 1.083; 95% CI, 0.595-1.969) for Asp allele, and those carriers of Asp allele (OR(adj) = 0.979; 95% CI, 0.771-1.243). Similarly, women who were TG heterozygotes (OR(adj) = 1.181; 95% CI, 0.842-1.658) or GG homozygotes (OR(adj) = 1.362; 95% CI, 0.746-2.486) and carriers of G allele (OR(adj) = 1.147; 95% CI, 0.903-1.458) were not associated with increased risk of breast cancer. Asp allele genotype was significantly associated with ER negativity (p = 0.0015) and poorly differentiated tumours (p = 0.008), but G allele genotype was not associated with the clinicopathological characteristics. In conclusion, Glu353Asp and T-885G polymorphic variants might not have an influence on breast cancer risk, thus might not be potential candidates for cancer susceptibility. Glu353Asp variant might be associated with tumour aggressiveness as defined by its association with ER negativity and poorly differentiated tumours.
    Matched MeSH terms: Intracellular Signaling Peptides and Proteins/genetics*
  13. Prevalence of anti cyclic citrullinated peptide antibodies in Malaysian rheumatoid arthritis patients and its correlation with disease activity
    Sockalingam S, Chow SK, Sthaneshwar P
    Int J Rheum Dis, 2009 Sep;12(3):211-5.
    PMID: 20374348 DOI: 10.1111/j.1756-185X.2009.01412.x
    AIM: The objectives of this study are to provide data regarding the prevalence of anti-cyclic citrullinated peptide (CCP) antibodies in Malaysian rheumatoid arthritis (RA) patients and to correlate the levels of anti-CCP antibody with the Disease Activity Score (DAS).
    METHOD: We studied the prevalence of anti-CCP antibodies in 51 RA patients attending our clinic and 29 controls. We also looked for correlation between anti-CCP antibody levels with the DAS and parameters such as duration of disease, rheumatoid factor (RF) and disease-modifying anti rheumatic drug (DMARD) usage.
    RESULTS: None of the controls demonstrated anti-CCP antibodies. Forty-one out of 51 patients (80.4%) were positive for anti-CCP antibodies. Sensitivity and specificity were 80.4% and 100% respectively in this study. Anti-CCP levels correlated significantly with rheumatoid factor, but no correlation was observed with the other parameters.
    CONCLUSIONS: Anti-CCP antibody is prevalent in Malaysian RA patients at 80.4% and more sensitive than RF in our cohort of established RA patients. Even though the anti-CCP levels correlated with RF, it did not show correlation with DAS.
    Matched MeSH terms: Peptides, Cyclic/immunology*
  14. Fulltext Diagnostic value of anti-modified citrullinated vimentin in rheumatoid arthritis
    Maraina CH, Nurdayana AK, Rusni D, Azwany Y
    Int J Rheum Dis, 2010 Oct;13(4):335-9.
    PMID: 21199468 DOI: 10.1111/j.1756-185X.2010.01552.x
    BACKGROUND: Rheumatoid factors (RF) are currently used in the diagnosis of rheumatoid arthritis (RA). Several other autoantibodies found in RA are directed to epitopes in citrullinated proteins such as anti-cyclic citrullinated and recently anti-modified citrullinated vimentin (MCV).
    OBJECTIVE: In this study we determined the sensitivity and specificity of anti-MCV in comparison with anti-cyclic citrullinated peptide (CCP) antibodies and RF in RA patients and in a control group using the American College of Rheumatology (ACR) criteria as the gold standard.
    MATERIALS AND METHODS: A cross sectional study was conducted from January to December 2008 on 100 patients with RA and 153 patients with arthritis or arthralgia but not fulfilling ACR criteria for RA. Serum from each subject was tested for anti-MCV, anti-CCP antibodies and immunoglobulin G (IgG) RF by enzyme-linked immunosorbent assay. Sensitivity and specificity of the tests were evaluated using the ACR criteria as the gold standard.
    RESULTS: The sensitivity of RF was 85% with 74.5% specificity. For anti-CCP antibodies the sensitivity was 71% and the specificity was 94.8%. The sensitivity of anti-MCV antibodies was 80% with 59.5% specificity. The area under the curve for RF was 0.759, for anti-CCP antibodies was 0.866 and for anti-MCV antibodies was 0.681, while for at least one positive test it was 0.691.
    CONCLUSION: Anti-CCP antibodies have higher diagnostic specificity and positive predictive value than RF and anti-MCV antibodies. RF has the highest sensitivity when compared to anti-CCP and anti-MCV antibodies. Thus anti-MCV antibody is not a better marker when compared to RF or anti-MCV antibody in the diagnosis of RA patients.

    Study site: family medicine clinic, rheumatology clinic and immunology laboratory of Hospital Universiti Sains Malaysia (HUSM), Kubang Kerian, Kelantan, Malaysia
    Matched MeSH terms: Peptides, Cyclic/immunology
  15. Fulltext The prevalence of rheumatoid factor isotypes and anti-cyclic citrullinated peptides in Malaysian rheumatoid arthritis patients
    Gomez EL, Gun SC, Somnath SD, D'Souza B, Lim AL, Chinna K, et al.
    Int J Rheum Dis, 2011 Feb;14(1):12-7.
    PMID: 21303477 DOI: 10.1111/j.1756-185X.2010.01573.x
    AIM: The purpose of this study is to compare the prevalence of rheumatoid factor (RF) isotypes and second generation anti-cyclic citrullinated peptides (anti-CCP) in Malaysian rheumatoid arthritis (RA) patients.
    METHODS: In this cross-sectional study, 147 established RA patients from three ethnic groups were recruited from a major rheumatology clinic in Malaysia. Enzyme-linked immunosorbent assays (ELISA) for serum RF isotypes IgA, IgG and IgM as well as second-generation anti-CCP were performed and the prevalence of each auto-antibody was compared in the three ethnic groups.
    RESULTS: The anti-CCP was the most prevalent auto-antibody in each of the ethnic groups, followed closely by RF IgM and RF IgG. Rheumatoid factor IgA was the least prevalent across all three ethnic groups. The anti-CCP-RF IgM combination provided the best test sensitivity. Seroprevalence of anti-CCP was strongly associated with the presence of each of the RF isotypes. The seroprevalence of RF and anti-CCP did not increase or decrease with advancing age, age at onset and disease duration.
    CONCLUSION: When used alone, anti-CCP provides a diagnostic advantage over RF IgM on the basis of test sensitivity. Considering the high cost of the anti-CCP assay, step-wise serum testing with IgM RF followed by anti-CCP may provide a more economically sensible option to optimize test sensitivity for RA.
    Study site: Rheumatology clinic, Hospital Tuanku Jaafar, Seremban, Negeri Sembilan, Malaysia
    Matched MeSH terms: Peptides, Cyclic/immunology*
  16. Exploring the mechanism of endothelial involvement in acidosis-induced vasodilatation of aortic tissues from normal and diabetic rats
    Yeo JL, Tan BT, Achike FI
    Eur J Pharmacol, 2010 Sep 10;642(1-3):99-106.
    PMID: 20553918 DOI: 10.1016/j.ejphar.2010.05.040
    Acidosis modulates physiologic and pathophysiologic processes but the mechanism of acidotic vasodilatation remains unclear. We therefore explored this in aortic rings from normal and streptozotocin-induced diabetic Sprague-Dawley rats. Phenylephrine (PE)-induced contraction in endothelium-intact and -denuded rings were recorded under normal and acidotic pH with or without drug probes. Acidosis exerted a relaxant effect in endothelium-intact and -denuded euglycaemic and diabetic tissues. l-NAME or methylene blue partially inhibited acidotic relaxation in these endothelium-intact but not the -denuded tissues, with greater inhibition in the diabetic tissues, indicating that acidosis induces relaxation by endothelium-dependent and -independent mechanisms, the former being EDNO-cGMP mediated. Indomethacin had no effect on the tissues, indicating that cyclooxygenase products are neither involved in acidosis-induced vasodilatation nor in the modulation of phenylephrine-contraction. In euglycaemic tissues under normal pH, no K(+) channel blocker altered phenylephrine-contraction, but all (except glibenclamide) enhanced diabetic tissue contraction, indicating that normally, these channels (K(ir), K(V), BK(Ca), K(ATP)) do not modulate phenylephrine-contraction, but they (except K(ATP)) are expressed in diabetes where they attenuate phenylephine-induced contraction and modulate acidosis. Only the K(ir) channel modulates acidotic relaxation in euglycaemic tissues. Only tetraethylammonium and iberiotoxin enhanced phenylephrine-induced contraction in endothelium-denuded diabetic tissues indicating that BK(Ca) attenuates phenylephrine-contraction and that acidotic relaxation in this condition is modulated by a tetraethylammonium-sensitive mechanism. In conclusion, acidosis causes vasodilatation in normal and diabetic tissues via endothelium-dependent and -independent mechanisms differentially modulated by a combination of a NO-cGMP process and K(+) channels, some of which are dormant in the normal state but activated in diabetes mellitus.
    Matched MeSH terms: Peptides/pharmacology
  17. Fulltext Epstein-Barr virus latent membrane protein-1 (LMP-1) 30-bp deletion and Xho I-loss is associated with type III nasopharyngeal carcinoma in Malaysia
    See HS, Yap YY, Yip WK, Seow HF
    World J Surg Oncol, 2008;6:18.
    PMID: 18275617 DOI: 10.1186/1477-7819-6-18
    Nasopharyngeal carcinoma (NPC) is a human epithelial tumour with high prevalence amongst Chinese in Southern China and South East Asia and is associated with the Epstein-Barr virus (EBV). The viral genome harbours an oncogene, namely, the latent membrane protein 1 (LMP1) gene and known variants such as the 30-bp deletion and loss of XhoI restriction site have been found. Less is known about the relationship between these variants and the population characteristics and histological type.
    Matched MeSH terms: Intracellular Signaling Peptides and Proteins/genetics*
  18. A comparative study of the expression of Wnt-1, WISP-1, survivin and cyclin-D1 in colorectal carcinoma
    Khor TO, Gul YA, Ithnin H, Seow HF
    Int J Colorectal Dis, 2006 May;21(4):291-300.
    PMID: 16041507
    BACKGROUND AND AIMS: It is well accepted that activation of Wnt signalling occurs in colorectal carcinoma (CRC), but the correlation amongst the various proteins involved in primary tumours are still unclear. The expression of the inducer of this pathway, Wnt-1, and the downstream effectors, WISP-1, cyclin-D1 and survivin proteins, was compared in a series of CRC tissues with the apparently normal adjacent tissues to determine the relationship of these proteins.

    PATIENTS AND METHODS: Formalin-fixed, paraffin-embedded tissue samples of 47 CRCs surgically resected at the Kuala Lumpur Hospital (KLH) between 1999 and 2000 were used. Immunohistochemical staining with monoclonal antibodies against cyclin-D1 and survivin and polyclonal antibodies against Wnt-1 and WISP-1 was performed. Results of immunohistochemistry were analysed for correlation between biomolecules and histopathological data of the patients.

    RESULTS: Of the 47 CRCs, 26 (55.3%), 15 (31.9%), 5 (10.6%) and 28 (59.6%) of the tumours exhibited positivity for Wnt-1, WISP-1, cyclin D1 and survivin, respectively. A lower percentage of the 40 apparently normal adjacent tissues were found to be positive for Wnt-1 (7, 17.5%), WISP-1 (+/-5, 12.5%) and survivin (13, 32.5%), but cyclin D1 was not detected in any of them. Interestingly, the total scores of Wnt-1, WISP-1 and survivin were significantly higher in CRC tissues (p=0.001, 0.034 and 0.044, respectively). Using the Spearman rank correlation test, a positive linear relationship was found between total Wnt-1 score with total WISP-1 score (rho=0.319, p=0.003) and total survivin score (rho=0.609, p=or<0.001). The expression of WISP-1 in the CRC tissues was found to be positively correlated with patients older than 60 years old (p=0.011). In addition, nuclear cyclin-D1 expression was found to be associated with poorly differentiated CRC tissues (p<0.001, Table 5) and right-sided CRC tumour (p=0.019, Table 6). Total WISP-1 score was associated with well-differentiated CRC tissues (p=0.029).

    CONCLUSIONS: Overexpression and interplay between Wnt-1, WISP-1, survivin and cyclin-D1 may play a role in tumorigenesis, possibly by promoting cell cycle checkpoint progression, accelerating cell growth and inhibiting apoptosis. Our data may provide useful information towards the search for potent therapeutic targets towards the development of novel treatment strategies for CRC.

    Matched MeSH terms: Intracellular Signaling Peptides and Proteins/metabolism*
  19. Serum and salivary IgA antibodies against a defined epitope of the Epstein-Barr virus nuclear antigen (EBNA) are elevated in nasopharyngeal carcinoma
    Foong YT, Cheng HM, Sam CK, Dillner J, Hinderer W, Prasad U
    Int J Cancer, 1990 Jun 15;45(6):1061-4.
    PMID: 1693600
    The Epstein-Barr virus nuclear antigen I (EBNA I) is the only latent EBV antigen consistently expressed in malignant tissues of the nasopharynx. A 20-amino-acid synthetic peptide, p107 contains a major epitope of EBNA I. We tested sera from 210 patients with nasopharyngeal carcinoma (NPC) and from 128 normal individuals (NHS) for IgA antibodies to p107 using an enzyme-linked immunosorbent assay (ELISA). Whereas 191/210 (91%) of NPC patients had IgA antibodies to p107, only 17/128 (13.3%) of NHS had such antibodies and only 6/57 (10.5%) of sera from patients with malignancies other than NPC had IgA-p107 reactivity. Thirty-nine salivary samples from 46 NPC patients (84.8%) also contained IgA-p107 antibodies whereas only 3/42 (7.1%) of normal saliva samples were IgA-p107 positive. The results suggest that IgA antibodies to EBNA I may become a useful, easily measurable, marker for NPC.
    Matched MeSH terms: Peptides/immunology
  20. Fulltext Unstable haemoglobin Köln disease in members of a Malay family
    Eng LL, Lopez CG, Eapen JS, Eravelly J, Wiltshire BG, Lehmann H
    J Med Genet, 1972 Sep;9(3):340-3.
    PMID: 5079107 DOI: 10.1136/jmg.9.3.340
    Matched MeSH terms: Peptides/analysis
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