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  1. Hamidi LR, Saaid R, Samberkar PN, Wong YP, Tan GC
    Malays J Pathol, 2024 Apr;46(1):117-118.
    PMID: 38682853
    No abstract available.
  2. Luena Victorio CB, Chua IL, Xu Y, Ng Q, Chua BH, Chow VTK, et al.
    Malays J Pathol, 2024 Apr;46(1):51-62.
    PMID: 38682844
    Small animal models play an important role in investigating and revealing the molecular determinants and mechanisms underlying neuro-virulence of enterovirus A71 (EV-A71). In our previous study, we successfully developed two mouse cell-line replication competent EV-A71 strains (EV71:TLLm and EV71:TLLmv) which were capable of inducing neuro-invasion in BALB/c mice. The more virulent EV71:TLLmv exhibited ability to induce acute encephalomyelitis accompanied by neurogenic pulmonary oedema. EV71:TLLcho virus strain was generated from EV71:TLLm by a series of passages in CHO-K1 cells. EV71:TLLcho demonstrated a broader range of infectivity across various mammalian cell lines and exhibited complete cytopathic effects (CPE) within 48 hours post-inoculation in comparison to EV71:TLLm or EV71:TLLmv. EV71:TLLcho consistently yielded higher levels of viral replication at all time points examined. In comparison to EV71:TLLm, EV71:TLLcho consistently induced more severe disease and increased mortality in one-week old BALB/c mice. However, unlike mice challenged with EV71:TLLmv, none of the mice challenged with EV71:TLLcho progressed to severe acute encephalomyelitis and developed neurogenic pulmonary oedema.
  3. Wong YP, Tan GC, Khong TY
    Malays J Pathol, 2024 Apr;46(1):41-49.
    PMID: 38682843
    INTRODUCTION: Identification of acute funisitis, a sign of foetal inflammatory response (FIR), is crucial as their presence is associated with ominous neonatal outcomes. Recommendation on which part of umbilical cord should be sampled to facilitate optimal identification of acute funisitis is limited.

    METHODS: This is a retrospective cross-sectional study over a seven-month duration recruiting all patients with clinical suspicion of chorioamnionitis and/or maternal intrapartum pyrexia. The distribution and the degree of cord inflammation were assessed. The cases were also evaluated for maternal inflammatory response (MIR) and chorionic vasculitis (CV).

    RESULTS: Of the 191 placentas, 88 (46.1%) had some degree of cord inflammation. Forty-nine (55.7%) had a differential in cord inflammation, with distal cord section (n = 38) demonstrating significant greater inflammation than that of proximal cord section (n = 11) (p<0.001). There were 20 cases with phlebitis only and 8 cases demonstrated arteritis only in either proximal or distal cord sections. Increasing magnitude of cord inflammation was significantly associated with increasing severity of MIR and the rate of CV (p<0.001). CV was observed in 25 (24.3%) cases showing absence of cord inflammation, while 12 (13.6%) cases with cord FIR demonstrated no CV.

    DISCUSSION: Inflammatory reaction can occur variably throughout the length of the umbilical cord and chorionic plate vessels, with greater inflammation seen in the distal cord section. We affirm the current Amsterdam recommendation of submitting at least two cross sections of the cord representing proximal and distal sites and two sections from placental parenchyma to facilitate the identification of FIR.

  4. Lim KG, Sumera A, Venkateswaran SP, Burud IAS, Albazah NIJ
    Malays J Pathol, 2024 Apr;46(1):11-20.
    PMID: 38682841
    Lymphomas are a diverse group of malignant proliferations that arise as discrete tissue masses. The most widely accepted taxonomy for lymphoma is the World Health Organization classification of tumours of haematopoietic and lymphoid tissues, the 5th edition of which was released in June 2022. Most (85% to 90%) lymphoid neoplasms are of B cell origin. Mature B-cell neoplasms are a heterogeneous group of malignancies with similar disease courses and treatment paradigms. This review focuses on the various mature B-cell lymphomas in Malaysia, including Hodgkin lymphoma. A literature search was performed in various bibliographic databases. A total of 64 papers were included in this review. We found 15 papers on Hodgkin lymphoma, 14 on follicular lymphoma, 12 on Burkitt lymphoma, 5 on mucosa-associated lymphoid tissue (MALT) lymphoma, 4 on plasmablastic lymphoma, 3 on mantle cell lymphoma, 1 each on primary mediastinal large B-cell lymphoma, B-lymphoblastic lymphoma, and 3 on other unspecified B-cell lymphomas. The site, age, distribution, prognostic markers, and the various subclassification of B cell lymphomas were studied from these papers. Prognostic genetic markers in B-cell lymphomas include C-MYC, BCL2 and BCL6 as they are the most prevalent mutations in this condition. Anecdotal outcomes range from rapid fatality to unexplained spontaneous remission. This review adds to the existing literature on lymphoma in Malaysia by compiling the evidence that may lead to further research on the diagnosis and treatment of lymphoma in Malaysia and worldwide.
  5. Paramanantham Y, B M Said NA, Mun KS
    Malays J Pathol, 2023 Apr;45(1):19-29.
    PMID: 37119243
    INTRODUCTION: Although epithelial-mesenchymal transition (EMT) and p53 have been established to play a pivotal role in the aggressiveness of muscle-invasive bladder cancer (MIBC), its pathological correlation to cisplatin treatment in the Malaysian patient cohort is lacking. This study aimed to evaluate the association of EMT markers, e-cadherin, vimentin and actin, as well as tumour suppressor gene, p53, in cisplatin-receiving MIBC patients.

    MATERIALS AND METHODS: Formalin-fixed paraffinembedded (FFPE) blocks of muscle-invasive bladder cancer patients receiving cisplatin-based chemotherapy between January 2010 to December 2020 were traced. Immunohistochemistry staining was performed on traced blocks using antibodies to e-cadherin, vimentin and actin, and p53.

    RESULTS: p53 and e-cadherin were stained positive in most cases (p=0.515 and 0.242 respectively), although e-cadherin showed stronger positive expression in pre-cisplatin receiving MIBC cases. All the cases stained negative for actin and vimentin except for faint staining observed in one pre-cisplatin case.

    CONCLUSION: Although this study does not show a significant correlation between EMT markers and p53 with cisplatin-responsiveness in MIBC patients, the results serve as preliminary findings on the heterogeneous outcomes of molecular staining in the Malaysian MIBC patient cohort.

  6. Chen Y, Chen K, Zhu W, Chen J, Huang Z
    Malays J Pathol, 2024 Aug;46(2):279-286.
    PMID: 39207004
    INTRODUCTION: Diabetic retinopathy is characterised by retinal vascular impairment. A number of aberrant microRNAs (miRNAs) have a role in the pathophysiology of vascular dysfunction. However, the relevance of miR-424 in retinal vascular endothelial cell dysfunction during hyperglycemia stress remains unknown. The purpose of this study is to investigate this issue.

    MATERIALS AND METHODS: Rhesus macaque choroid retinal endothelial cell line (RF/6A) cells were cultivated in normal glucose (NG) and high glucose (HG) conditions. The mRNA expression of miR-424 and Cyclin D1 (CCND1) was quantified using qPCR, and the protein quantity of CCND1 was detected using Western Blot. miR-424 mimics, miR-424 inhibitors, miR-424 inhibitor+ siRNA-CCND1 or vehicle molecules were transfected into RF/6A cells. MTT test was used to assess cell proliferation, and flow cytometric analysis was used to assess cell cycle. The interaction between miR-424 and CCND1 was predicted using bioinformatics and validated using dual luciferase reporter analysis.

    RESULTS: miR-424 was up-regulated, and cell viability was reduced in HG compared to NG. By reversing the expression of miR-424 in certain situations, the phenotypes can be changed. CCND1 has been identified as a miR-424 target gene, and it may be regulated at the transcriptional and translational levels. Manipulation of silencing CCND1 can counteract the effect of transfecting miR-424 inhibitor into RF/6A cells under HG such as proliferation stimulation.

    CONCLUSIONS: Our findings indicate that miR-424 plays an important role in hyperglycemia induced ARPE-19 cells damage, and it could be a new therapeutic target for DR by preventing retinal vascular cells from HG-induced injury.

  7. Hoo R, Shelat VG
    Malays J Pathol, 2023 Aug;45(2):285-292.
    PMID: 37658538
    INTRODUCTION: Hepatocellular carcinoma is the most common primary liver malignancy, and sarcomatoid hepatocellular carcinoma is a rare malignancy containing both carcinomatous and sarcomatous components.

    CASE REPORT: We report a 64-year-old male patient treated with open right trisectionectomy for a 16cm right hemiliver tumour. The diagnosis of sarcomatoid hepatocellular carcinoma was confirmed on histology. Five months after hepatic resection, patient had symptoms suggestive of Horner's syndrome along with left sided shoulder pain, hand weakness, reduced power of the intrinsic hand muscles and reduced pain perception over the C8/T1 dermatome. Magnetic Resonance Imaging (MRI) showed a mass at the left lung apex/superior sulcus involving the left C8, T1 nerve roots, scalene muscles, and brachial plexus. The mass closely abutted the left first rib and partially encased the left subclavian artery. The patient was managed with palliative chemoradiotherapy for Pancoast syndrome.

    DISCUSSION: Hepatocellular carcinoma pulmonary metastasis causing Pancoast syndrome is a rare occurrence with only four prior reports, and to the best of our knowledge, pulmonary metastasis from sarcomatoid hepatocellular carcinoma causing Pancoast syndrome is unreported. In this report, we will discuss the clinicopathological characteristics of this case which may provide insight into diagnosis and management of other sarcomatoid hepatocellular carcinoma patients.

  8. Mohd Kasim NA, Mohd Nor NS, Wen MT, Syed Kamaruddin SKA, Sheikh Abdul Kadir SH
    Malays J Pathol, 2023 Aug;45(2):293-296.
    PMID: 37658539
    INTRODUCTION: A 1-year-old Malay girl presented with pallor, failure to thrive and hepatosplenomegaly. Her blood was sent for thalassaemia screening and it was incidentally found that her blood appeared lipaemic.

    CASE REPORT: Primary and secondary causes of hyperlipidaemia were investigated. Her blood was sent for fasting lipid profile, thyroid function test (TFT), fasting plasma glucose (FPG), liver function test (LFT), renal profile (RP) and HIV screening. Lipaemic interference was removed by high-speed centrifugation. She is a product of non-consanguineous marriage. She is staying together with her stepfather who is HIV positive. Her mother's infective status was negative with no dyslipidaemic features and a normal lipid profile. Lipid profile of her biological father was not known. No other lipid stigmata such as eruptive xanthoma or lipaemia retinalis was seen in the patient. Haemoglobin analysis showed Hb E-Beta thalassaemia major. Her triglycerides was 9.05 mmol/L with normal total cholesterol, 2.85 mmol/L and high-density lipoprotein cholesterol (HDL-c), 0.26 mmol/L. Calculated low-density lipoprotein cholesterol (LDL-c) was invalid as triglycerides was >4.5 mmol/L. TFT, RP, FPG, LFT were normal and HIV status was negative. She was transfused with 10 ml/kg packed cell and her blood post transfusion appeared non lipaemic.

    CONCLUSION: Primary hypertriglyceridaemia was excluded based on insignificant family history of dyslipidaemia. Secondary causes of hypertriglyceridaemia were ruled out based on unremarkable laboratory investigations. Thus, we conclude that this patient is having hypertriglyceridaemia thalassaemia syndrome (HTS) which is a rare disorder with unknown pathogenesis. Further research may be required to explore this unknown association.

  9. Ng CT, Yip WK, Mohtarrudin N, Jabar MF, Seow HF
    Malays J Pathol, 2023 Aug;45(2):195-204.
    PMID: 37658529
    INTRODUCTION: Extracellular vesicles (exosome-like vesicles) are small membrane vesicles ranging from 20-200nm in size that are released by various cells into the extracellular space. These extracellular vesicles play a major role in cell-to-cell communication and contain materials, such as proteins, mRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). The effect of exosomes derived from an invasive colon cancer cell line on angiogenesis is unclear. Hence, the aim of this study is to investigate the effect of exosomes derived from an invasive colon cancer cell line on angiogenesis of endothelial cells.

    MATERIALS AND METHODS: In the present study, the exosomes from the cell culture supernatants of an invasive colon cancer cell line SW480-7 were characterised. The effect on tube formation and expression of angiogenic genes in a microvascular endothelial cell, telomerase-immortalised microvascular endothelial cell (TIME) was examined after co-cultured with exosomes secreted from SW480-7.

    RESULTS: Zetasizer result showed average diameter of exosomes derived from SW480-7 was 246.2 nm and morphological analysis showed the size of majority of exosomes were less than 200 nm. Results showed that exosomes derived from SW480-7 increased tube formation and up-regulated FGFR3 mRNA expression in TIME.

    CONCLUSION: Our findings suggest that exosomes derived from SW480-7 increased tube formation and up-regulated expression of FGFR3 mRNA in TIME.

  10. Ali U, Zainal M, Zainol Z, Tai CW, Tang SF, Lee PC, et al.
    Malays J Pathol, 2023 Aug;45(2):215-227.
    PMID: 37658531
    INTRODUCTION: Acute respiratory infection (ARI) contributes to significant mortality and morbidity worldwide and is usually caused by a wide range of respiratory pathogens. This study aims to describe the performance of QIAstat-Dx® Respiratory Panel V2 (RP) and RespiFinder® 2SMART assays for respiratory pathogens detection.

    MATERIALS AND METHODS: A total of 110 nasopharyngeal swabs (NPS) were collected from children aged one month to 12 years old who were admitted with ARI in UKMMC during a one-year period. The two qPCR assays were conducted in parallel.

    RESULTS: Ninety-seven samples (88.2%) were positive by QIAstat-Dx RP and 86 (78.2%) by RespiFinder assay. The overall agreement on both assays was substantial (kappa value: 0.769) with excellent concordance rate of 96.95%. Using both assays, hRV/EV, INF A/H1N1 and RSV were the most common pathogens detected. Influenza A/H1N1 infection was significantly seen higher in older children (age group > 60 months old) (53.3%, p-value < 0.05). Meanwhile, RSV and hRV/EV infection were seen among below one-year-old children. Co-infections by two to four pathogens were detected in 17 (17.5%) samples by QIAstat-Dx RP and 12 (14%) samples by RespiFinder, mainly involving hRV/EV. Bacterial detection was observed only in 5 (4.5%) and 6 (5.4%) samples by QIAstat-Dx RP and RespiFinder, respectively, with Mycoplasma pneumoniae the most common detected.

    CONCLUSION: The overall performance of the two qPCR assays was comparable and showed excellent agreement. Both detected various clinically important respiratory pathogens in a single test with simultaneous multiple infection detection. The use of qPCR as a routine diagnostic test can improve diagnosis and management.

  11. Abd Rahim A, Muhammad R, Ismail F, Wong YP, Che Abdul Aziz R, Chong GY, et al.
    Malays J Pathol, 2023 Aug;45(2):275-283.
    PMID: 37658537
    Thyroid carcinoma is uncommon. Papillary thyroid carcinoma (PTC) represents the majority of differentiated thyroid carcinoma and is a recognised complication of prior exposure to ionizing radiation. Even more uncommon is the synchronous occurrence of PTC with Hodgkin lymphoma (HL) as multiple primary malignancies. We report a 33-year-old mother of three who developed asymptomatic thyroid nodule for four years, and neck swelling for the recent ten months. She denied constitutional symptoms or B symptoms, and thyroid profiles were normal. Initially, metastatic thyroid cancer was suspected based on ultrasound scan findings of enlarged left thyroid gland and enlarged supraclavicular lymph nodes (LN). However, fine needle aspiration examinations of the thyroid nodule were inconclusive, and the supraclavicular LN was suspicious of HL. Computerised tomography scan detected a large mass at the thyroid glands and lymphadenopathies in the mediastinal, hilar, subcarinal and axilla with dimensions up to 6 cm. Left hemi-thyroidectomy with left supraclavicular LN biopsy revealed PTC in the left thyroid lobe measuring 38 x 25 x 18 mm, and the left supraclavicular LN was not definitive of HL. Completion thyroidectomy on the right side, bilateral central neck dissection and excision biopsy of the right supraclavicular LN revealed the presence of HL in the right supraclavicular LN, and both HL and metastatic PTC in right central LN. After multidisciplinary discussions, the patient received chemotherapy at four weeks postoperatively and achieved complete remission. This report highlights the importance of patient-centered approach and multidisciplinary consensus within lack of established guidelines, given rarity of the case.
  12. Faiz M, Rashid F
    Malays J Pathol, 2023 Aug;45(2):205-214.
    PMID: 37658530
    INTRODUCTION: Mutations in FLT3 are the most commonly reported genetic changes in AML patients. These mutations are normally identified in approximately one third of newly diagnosed patients and are reported to have prognostic significance.

    MATERIALS AND METHODS: Peripheral blood samples was collected from 63 AML patients to study their morphological, cytogenetic and molecular features. PCR was used to determine the prevalence of FLT3 mutations; internal tandem duplication (ITD) and tyrosine kinase domain (TKD) in AML patients.

    RESULTS: Among 63 AML patients, 42 were males and 21 were females with male to female ratio 2:1 with median age of 32 years. AML-M2 was the predominant French-American-British (FAB) subtype (42%) followed by M4 (27%), M3 (8%), M1 (8%), M0 (8%) and M5 (7%) respectively. Cytogenetic analysis of 60 patients showed 58% as cytogenetically normal (CN) whereas 42% had aberrant karyotype.The most frequent aberrations were trisomy8, t(8;21), t(15;17) (8.3%) each, inversion16 (5%), and different deletions (12%) respectively. FAB-M4 subtype showed most of the chromosomal anomalies. Among 63 AML patients, 22% showed FLT3/ITD while 6.4% had D835 mutation after molecular analysis. FLT3 mutations were found in most of the FAB subtypes and cytogenetic groups. FLT3/ITD mutations were more common in patients with normal karyotype (26%) and usually present with hyperleukocytosis but association between two was not significant.

    CONCLUSION: The cytogenetic data of adult AML from Pakistan showed presence of favourable prognostic karyotype with comparable prevalence as reported in international data. Moreover, FLT3/ITD mutations are commonly found in our patients as determined by molecular analysis. Therefore, inclusion of this unfavourable prognostic marker should be routine in molecular diagnostic testing of AML.

  13. Goh JJ, Ong HT, Lee BS, Teoh HK
    Malays J Pathol, 2023 Aug;45(2):247-259.
    PMID: 37658534
    INTRODUCTION: Mesenchymal stromal cells (MSCs) are promising vehicles for cancer therapy due to their homing ability and potency to be genetically manipulated through either viral or non-viral methods. Interleukin-12 (IL-12) is one of the key immunomodulatory cytokines which has anti-tumour effect. However, systemic administration of the cytokine at therapeutic dosage can cause serious toxicity in the host system due to the high systemic level of interferon-γ (IFN-γ) induced.

    OBJECTIVES: This study aimed to investigate the in vitro growth inhibition of genetically engineered human umbilical cord-derived mesenchymal stromal cells (hUCMSC) expressing IL-12 on H1975 human lung adenocarcinoma cells.

    MATERIALS AND METHODS: Both adenoviral method and electroporation which used to generate hUCMSC-IL12 were compared. The method with better outcome was selected to generate hUCMSC-IL12 for the co-culture experiment with H1975 or MRC-5 cells. Characterisation of hUCMSC and hUCMSC-IL12 was performed.

    RESULTS: Adenoviral method showed superior results in transfection efficiency (63.6%), post-transfection cell viability (82.6%) and hIL-12 protein expression (1.2 x 107 pg/ml) and thus was selected for the downstream experiments. Subsequently, hUCMSC-IL12 showed significant inhibition effect on H1975 cells after 5 days of co-culture. No significant difference was observed for all other co-culture groups, indicating that the inhibition effect was because of hIL-12. Lastly, the integrity of hUCMSC-IL12 remained unaffected by the transduction through examination of their surface markers and differentiation properties.

    CONCLUSION: This study provided proof of concept that hUCMSC can be genetically engineered to express hIL-12 which exerts direct growth inhibition effect on human lung adenocarcinoma cells.

  14. Poh KY, Jackson N
    Malays J Pathol, 2023 Aug;45(2):187-194.
    PMID: 37658528
    INTRODUCTION: Inappropriate use of blood and blood products has been well reported from many countries including Malaysia and may be due to a deficit of transfusion medicine (TM) knowledge. This study is aimed to assess TM knowledge among clinicians in a tertiary hospital.

    MATERIALS AND METHODS: The validated exam developed by the BEST collaborative group was used to assess TM knowledge of doctors, from junior residents up to senior specialists. Scores of 42%, 62%, and 82%, corresponding to basic, intermediate, and expert levels of knowledge, respectively. Convenience sampling was done from eight blood-using departments at University Malaya Medical Centre. The Kruskal-Wallis test was used to compare the candidates' exam scores between different variables.

    RESULTS: A total of 184 doctors were assessed. The overall mean score was 40.1% (SD 12.7%). The most senior doctors had a significantly lower mean score compared with resident trainees and specialists. Doctors from haematology, anesthesiology, and internal medicine had significantly higher scores (51%, 47.4%, and 46.4% respectively, p<0.05). No correlations were found between the exam scores and the self-reported amount, or quality of prior TM teaching, nor with the year of postgraduate training. Participants did poorly on questions related to transfusion reactions, especially the question on transfusion-related acute lung injury.

    CONCLUSION: Inadequate transfusion medicine knowledge was found across all the departments and levels of appointment. It is concerning that the most senior decision-making doctors had especially poor knowledge. TM training is needed by all residents, and regular updates should be given to established specialists.

  15. Tan CX, Yeo SW, Wong YP, Tan GC
    Malays J Pathol, 2023 Aug;45(2):271-273.
    PMID: 37658536
    INTRODUCTION: Lymphangiomatous polyp of the tonsil is generally accepted as a hamartomatous lesion. Its differential diagnosis includes fibroepithelial polyp, squamous papilloma, angiofibroma, haemangioma, arteriovenous malformation, hamartoma and lymphangioma.

    CASE REPORT: A 33-year-old man presented with 2 months history of feeling of foreign body sensation in the throat. Examination revealed a nodular red coloured polyp on the left tonsil. Histologically, the polyp was covered by squamous epithelium and is composed of numerous vascular channels containing lymphocytes and eosinophilic material, in a fibrous stroma. Immunohistochemically, the endothelial cells were positive toward CD31 and D2-40.

    DISCUSSION: The characteristic histological features of a lymphangiomatous polyp are benign vascular proliferation with variable fibrous, adipose and lymphoid stromal components. Nested intraepithelial epidermotropism of lymphocytes can be observed. The vascular channels are typically thin-walled and contain eosinophilic proteinaceous material and lymphocytes. There is no reported incidence of recurrent or malignant transformation.

  16. Anthony R, Rajandram R, Yap NY, Mun KS, Samberkar PN, Kuppusamy S
    Malays J Pathol, 2023 Aug;45(2):261-269.
    PMID: 37658535
    BACKGROUND: Ubiquitously Transcribed Tetracopeptide Repeat on X Chromosome (UTX) and Jumonji Domain-Containing Protein 3 (JMJD3) are histone H3 lysine 27 (H3K27) demethylases that are found to play tumour suppressor or oncogenic roles in many cancers. However, their roles in urothelial carcinoma (UC) have not been well studied.

    OBJECTIVE: This study investigated UTX and JMJD3 protein expression patterns in UC and assess their clinical significance.

    PATIENTS AND METHODS: Immunohistochemistry (IHC) method was performed on formalin-fixed paraffin-embedded (FFPE) of UC tissues and compared to the normal bladder tissues from the autopsy specimen. The staining intensity of FFPE tissues were captured with the nuclear and overall positive pixels quantified using Aperio ImageScope software.

    RESULTS: JMJD3 protein uptake was present in both nucleus and cytoplasm but UTX protein was predominantly seen in the cytoplasm of UC tissue. UTX was under expressed whereas JMJD3 was over expressed in UC compared to normal bladder. UTX and JMJD3 were not related to clinical stage and grade. However, significant association between JMJD3 expression and invasiveness of tumour (p<0.05) was noted, especially in MIBC group (88.9%). UTX and JMJD3 did not yield any significance as prognostic factors for diseasespecific survival.

    CONCLUSIONS: Low expression of UTX protein in UC may indicate possible loss of its tumour suppressor activity and higher JMJD3 protein expression may indicate oncogenic activity. Hence, JMJD3 protein could be a potential diagnostic biomarker in detecting bladder UC of higher stages. Further investigation needed to study the dysregulation of this protein expression with associated gene expression.

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