Malaysian Journal of Pathology最新文献

Introduction: Candida albicans and Streptococcus mutans co-exist in biofilms in the oral cavity. In this study, the impact of S. mutans on the growth of C. albicans within a mixed-species biofilm was examined.

Materials and methods: Single species C. albicans biofilms and mixed species biofilms containing C. albicans and S. mutans at 1:3 and 1:10 ratios were constructed in 6-well microtiter plates. After 24 hours of incubation, the density of resuspended biofilm cells was determined as CFU/ml and used to compare the growth of C. albicans in single species and mixed species biofilms.

Results: The CFU/ml of C. albicans in mixed-species biofilms was found to be higher than that in single-species biofilms.

Conclusion: S. mutans promotes the growth of C. albicans in a co-inhabited biofilm.

Introduction: Leukaemia is the most common cancer in children, however, there is still a big gap in knowledge about the genomic alterations in childhood acute myeloid leukaemia (AML) compared to adult AML. Relapsed AML remains as a leading cause of cancer deaths among children. This study aims to understand the molecular mechanisms of relapsed AML by elucidating the mutational landscape before and during relapse.

Materials and methods: Whole genome sequencing was performed on matched samples collected at diagnosis, remission and relapse from three patients of de novo childhood AML. Sanger sequencing was performed for validation in 47 patients' samples, followed by functional analysis.

Results: Overall, we identified 312 somatic mutations including synonymous single nucleotide variants (SNVs), missense SNVs, deletions and insertion frameshifts, stopgains and splice sites. After prioritisation, only 46 variants were present at diagnosis (13-17 mutations per patient) and 49 variants at relapse (12-20 mutations per patient). Out of 81 variants, there were 35 new variants detected at relapse but not present at diagnosis. Six potential driver mutations (KIT, CDC73, HNF1A, RBM10, ZMYM4 and ETV6) were identified in predicting relapse for the 3 patients, with recurrent mutations of the ETV6 gene in 2 patients. Functional analysis of the ETV6 mutation showed that ETV6 lost its tumour suppressive function when both mutant ETV6 p.P25fs and ETV6 p.N75fs were tested in vitro.

Conclusion: This study has uncovered the mutational landscape in three local childhood AML patients and contributes to a better understanding of the molecular mechanisms of relapsed AML.

No abstract available.

Introduction: Haemoglobin (Hb) Quong Sze is a non-deletional α-thalassaemia subtype that occurs due to missense mutation at codon 125 of the HBA2 gene. Interaction between Hb QS with Southeast Asian double α-globin gene deletion results in non-deletional HbH disease, which is more severe than deletional HbH.

Case report: A 3-month-old baby boy was presented with neonatal anaemia and mild hepatomegaly. Full blood count revealed severe hypochromic microcytic anaemia. There was an abundance of HbH inclusion bodies in his red blood cells. High-performance liquid chromatography showed a reduced HbA2 level with the presence of pre-run peak. Capillary electrophoresis showed the presence of HbH and Hb Barts. Molecular analysis found a common α⁰-thalassaemia (--^SEA) in one allele and mutation in codon 125 in the other allele.

Discussion: Non-deletional HbH disease due to a combination of deletional and non-deletional mutations may present with severe clinical manifestations than those with deletion mutations, which warrants accurate diagnosis using molecular techniques.

Congenital Adrenal Hyperplasia (CAH) is primarily caused by mutations in genes responsible to produce enzymes involved in the synthesis of cortisol, aldosterone, or both. This study aims to determine the prevalence, sociodemographic distributions, and clinical factors associated with CAH in the Malaysian population. This retrospective study reviewed laboratory records of 17-hydroxyprogesterone (17OHP) test requests received at the Institute for Medical Research, Kuala Lumpur from January 2021 to December 2021. Descriptive statistics were employed for most variables, and logistic regression analysis was conducted to determine factors associated with CAH. The dataset included a total of 775 patients (64.2%) from 1,207 test requests screened. The prevalence of newly diagnosed CAH in the year 2021 was 13.5% (n=105). The majority were Malays (15.1%), neonates (13.8%), and females (45.7%). Higher baseline 17-OHP (cOR:1.31, 95% CI:1.19, 1.45), unknown gender at birth (cOR:7.82, 95% CI:2.86, 21.37), and neonatal age group at presentation (cOR:29.3, 95% CI:12.07, 71.03) independently predict CAH. The high prevalence of CAH in our region has been speculated to be due to the cultural consanguinity norms, resulting in genetic aberrations. CAH may manifest as ambiguous genitalia, particularly in females, due to the overproduction of androgens in-utero, resulting in atypical genitalia, necessitating thorough investigation. To the best of our knowledge, the data presented are the latest report on CAH prevalence, distribution, and description of positive CAH cases in the Malaysian population. These findings are essential for further public health planning to improve the diagnostic capacity and clinical management of CAH.

Introduction: Thalassemia and haemoglobinopathies are relatively common among Malaysians. One of the rare haemoglobinopathies reported is Haemoglobin (Hb) Arya, which occurs due to substitution of aspartic acid at residue 47 of the alpha chain by asparagine. Here, we report the detection of Hb Arya in a Malaysian family, which was detected incidentally during family screening.

Case report: A 16 years-old girl, clinically asymptomatic was noted to have low mean corpuscular haemoglobin (MCV) with normal Hb level. Hb analysis using capillary electrophoresis (CE) showed reduced Hb A of 76.5%, Hb A2 of 1.6% with presence of small peak at Zone 1 likely A2'. There was also a small peak noted at Hb D zone and Hb S zones which quantified as 1.5% and 20% respectively. Supplementary test by high performance liquid chromatography (HPLC) showed a prominent peak at D-window (19.6%) and a small peak at S-window (0.6%). DNA analysis revealed a heterozygous state of α2 codon 47 Hb Arya mutation. Subsequent family study showed a similar mutation in the father and sister of the index case.

Conclusion: Very few reports are available up to date regarding Hb Arya. This report highlights the rare haemoglobinopathy in a Malay family in Malaysia that contributes to the growing literature of this rare haemoglobin variant.

Introduction: Electrocution related death remains an ambiguous judgement and requires numerous valid evidence for proper medico-legal diagnosis. While the presence of electrical burn marks is a significant macroscopic indicator, it can be absent, especially on moist skin. The electrical mark still represents a fundamental indicator above all in the medico-legal field, but the identification of pathognomonic elements and signs not limited to the skin alone could be a valid help in the future, especially in unclear cases.

Case report: The deceased was brought-in-dead to the hospital from their workplace, with no signs of fatal natural diseases. External examination revealed a Y-shaped burn mark on the right side of the neck and collapsed blisters with greying rings on both heels. Internal examination showed no alarming findings. Further, histopathological analysis of the foot blisters and neck burn revealed intraepidermal detachment, elongated nuclei, and coagulative necrosis. Notably, the presence of muscle fibre casts in kidney tubules and microthrombi in lung sections which indicate rhabdomyolysis and vascular thrombosis supported electrocution-related death.

Conclusion: These positive findings of the electrical burn marks externally and significant histopathological changes, collectively support the death was due to electrocution, after excluding any major, fatal injuries. Albeit, a detailed inspection of the crime scene plays an important role, in order to classify the electrocution related death.

Diagnosis of extraintestinal microsporidiosis is always hampered due to non-specific symptoms and difficulty in diagnosis. This study aimed to compare the diagnostic utility of blood and faecal-based polymerase chain reaction (PCR) to detect microsporidiosis in immunocompromised patients. A total of 42 immunocompromised patients consisting of HIV-infected and chemotherapy-treated patients were enrolled. Paired faecal and blood samples were collected and subjected to PCR to detect Enterocytozoon bieneusi and Encephalitozoon spp. Faecal samples were microscopically screened for microsporidia spores. Overall, 42.9% (18/42) of patients were positive for microsporidiosis. Of this, 19.0% (8/42) and 4.8% (2/42) were positive by blood and stool PCR respectively. Meanwhile, 33.3% (14/42) of the faecal specimens were microscopically positive. Among the positive patients, 22.2% (4/18) had microsporidia confirmed by blood PCR and stool microscopy, suggestive of dissemination. Interestingly, the stool specimen in which microsporidia spores were detected via microscopy is not positive via PCR method. This highlights the limitation of the faecal-based detection method and the important use of blood samples for diagnosing extraintestinal microsporidiosis. Only E. bieneusi species were detected in all PCR-positive samples. This study highlights the diagnostic value of blood PCR in diagnosing extraintestinal microsporidiosis infections.

Introduction: The prevalence of suicide presents a significant public health challenge globally, affecting diverse populations around the world. This study is motivated by the urgency to tackle suicide as a crucial public health issue on a global level, according to the United Nations Sustainable Development Goals and the General Programme of Work and Mental Health Action by the World Health Organization.

Materials and methods: The research was performed at the Forensic Unit of Hospital Canselor Tuanku Muhriz, spanning a retrospective analysis covering 2012 to 2021. A descriptive analysis was conducted to analyse the patterns of suicide and the sociodemographic characteristics of the cases.

Results: The findings show monthly variations and a recent increase in suicide rates, especially during the pandemic of COVID-19. Analysis of suicide methods indicates that hanging is the most common suicide method, which accounts for almost half of the sample population, followed by jumping from a height and burning charcoal. Adult males are primarily implicated in suicidal acts, and the study reveals unique trends among different age groups, genders and employment statuses.

Conclusion: This study aims to offer thorough insights and comprehension into suicide within the Malaysian sociodemographic framework. Consequently, it could furnish valuable insights for public health authorities and governmental bodies.

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.