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Understanding the dynamics of COVID-19; implications for therapeutic intervention, vaccine development and movement control

Salvamani S, Tan HZ, Thang WJ, Ter HC, Wan MS, Gunasekaran B, et al.

Br J Biomed Sci, 2020 Oct;77(4):168-184.
PMID: 32942955 DOI: 10.1080/09674845.2020.1826136

The COVID-19 disease is caused by the SARS-CoV-2 virus, which is highly infective within the human population. The virus is widely disseminated to almost every continent with over twenty-seven million infections and over ninety-thousand reported deaths attributed to COVID-19 disease. SARS-CoV-2 is a single stranded RNA virus, comprising three main viral proteins; membrane, spike and envelope. The clinical features of COVID-19 disease can be classified according to different degrees of severity, with some patients progressing to acute respiratory distress syndrome, which can be fatal. In addition, many infections are asymptomatic or only cause mild symptoms. As there is no specific treatment for COVID-19 there is considerable endeavour to raise a vaccine against SARS-CoV-2, in addition to engineering neutralizing antibody interventions. In the absence of an effective vaccine, movement controls of varying stringencies have been imposed. Whilst enforced lockdown measures have been effective, they may be less effective against the current strain of SARS-CoV-2, the G614 clade. Conversely, other mutations of the virus, such as the Δ382 variant could reduce the clinical relevance of infection. The front runners in the race to develop an effective vaccine focus on the SARS-Co-V-2 Spike protein. However, vaccines that produce a T-cell response to a wider range of SARS-Co-V-2 viral proteins, may be more effective. Population based studies that determine the level of innate immunity to SARS-CoV-2, from prior exposure to the virus or to other coronaviruses, will have important implications for government imposed movement control and the strategic delivery of vaccination programmes.
British Journal of Biomedical Science in 2020. What have we learned?

Brown NW, Orchard G, Rhodes A

Br J Biomed Sci, 2020 Oct;77(4):159-167.
PMID: 33252323 DOI: 10.1080/09674845.2020.1827578

Each year the British Journal of Biomedical Science publishes a 'What have we learned' editorial designed to introduce readers within the major disciplines of laboratory medicine to developments outside their immediate area. In addition it is designed to inform a wider readership of the advances in the diagnosis and treatment of disease. To this end, in 2020 the journal published 39 articles covering the disciplines within Biomedical Science in the 4 issues comprising volume 77. These included a review of COVID-19 in this issue, 27 original articles, 6 Biomedical Science 'In Brief' and 4 case histories. 27 of the articles involved molecular techniques, with one of these comparing results with a mass spectrometry based method. The preponderance of molecular genetic studies gives us a good idea of the likely future direction of the disciplines.
British Journal of Biomedical Science in 2021. What have we learned?

Orchard G, Rhodes A, Brown NW

Br J Biomed Sci, 2021 10;78(4):159-166.
PMID: 34850663 DOI: 10.1080/09674845.2021.1982279
Role of interleukin-1beta and tumour necrosis factor-alpha on hydroxyapatite-induced phagocytosis by murine macrophages (RAW264.7 cells)

Gopinath VK, Musa M, Samsudin AR, Sosroseno W

Br J Biomed Sci, 2006;63(4):176-8.
PMID: 17201208
Hybridisation analysis for serum hepatitis B virus DNA

Yap SF, Wong PW, Kenneth-Raj

Br J Biomed Sci, 1994 Dec;51(4):336-40.
PMID: 7756940

A study was carried out to determine optimal assay conditions for an in-house hybridisation assay for detection of hepatitis B virus (HBV) genome in serum samples. Pre-treatment of samples, blot treatment and hybridisation conditions were found to affect assay performance. The indirect serum blot procedure was more robust and reliable than direct serum blotting. In the former, viral particles were isolated from the sample, lysed and then extracted. In comparison, no approaches to the direct serum spot method performed adequately. Sensitivity studies showed that labelling of the nucleic acid probe with dCTP was more efficient than with dATP. Using probes labelled to a specific activity of > 1 x 10(8) and an autoradiography period of about 48 h we could achieve a detection limit of < 1 pg. Specificity was achieved by use of a highly purified probe and moderately stringent hybridisation and wash conditions. Background binding was minimal and there was no non-specific binding of probe to negative control samples. Factors affecting speed of the assay were studied to identify steps that could be modified to shorten assay time without sacrificing performance. A shorter centrifugation step and the use of a high specific-activity probe permitted completion of an assay within four days.
Immunoassay of gonadotropins using a fully-automated benchtop analyser

Kamariah K, Lopez JB, Satgunasingam N

Br J Biomed Sci, 1994 Sep;51(3):296-8.
PMID: 7881328

We assessed the analytical performance of the Abbott IMxTM immunoassay analyser for total beta human chorionic gonadotropin (Beta hCG), follicle-stimulating hormone (FSH) and luteinising hormone (LH). The within-run CVs for various analyte concentrations were 2% to 6% while those for between-run imprecision in routine assay ranged from 4% to 10%. IMxTM values correlated well with radioimmunoassay for beta hCG, and immunoradiometric assay for FSH and LH; the correlation coefficients (r) were 0.97, 0.99 and 0.98 for total beta hCG, FSH and LH respectively. The average sensitivities were approximately 3.1, 0.2 and 0.5 iu/l for beta hCG, FSH and LH, respectively. Sample carry-over was not detected and there was negligible cross-reaction between LH and beta hCG in the respective assays. The automatic sample dilution protocol for beta hCG was superior to the manual procedure. The IMxTM is easy to operate and is able to process 24 samples in 40-45 minutes.
Hepatitis markers in Malaysians with hepatocellular carcinoma

Lopez JB, Thambyrajah V, Balasegaram M, Satgunasingam N

Br J Biomed Sci, 1994 Jun;51(2):177-80.
PMID: 7519505

Sera from 80 Malaysians with confirmed hepatocellular carcinoma were tested for five markers of the hepatitis B virus, anti-HCV and anti-HDV by enzyme immunoassay, and alpha fetoprotein (AFP) was measured by radioimmunoassay. Of the patients, 98.8% had evidence of HBV infection and 75% were positive for HBsAg--which latter correlated with AFP raised above cut-off values of 500 ng/ml (P = 0.0001) and 200 ng/ml (P = 0.005). Males correlated significantly with the presence of HBsAg (P = 0.002). Thirty-one per cent of HBsAg positive patients were also positive for HBeAg and 74% for anti-HBe. Twenty per cent of the cases were concurrently positive for both HBsAg and anti-HBs. Six of 70 (8.6%) patients were positive for anti-HCV, of whom four were also positive for HBsAg. None of 67 patients tested for anti-HDV were positive. The results strongly indicate an important aetiological role for hepatitis B virus in causation of hepatocellular carcinoma among Malaysians.
Expression of WT1 and PAX8 in the epithelial tumours of Malaysian women with ovarian cancer

Rhodes A, Vallikkannu N, Jayalakshmi P

Br J Biomed Sci, 2017 Apr;74(2):65-70.
PMID: 28367736 DOI: 10.1080/09674845.2016.1220709

BACKGROUND: Ovarian cancer is particularly lethal due to late stage at presentation. The subtypes behave differently with respect to their biology and response to treatment. Two recent markers reported to be useful in assisting in the diagnosis are WT1 and PAX8. Malaysia, with its multi-ethnic population provides an opportunity to study the expression of these biomarkers in ovarian cancer in the three most populous ethnicities in Asia and ascertain their usefulness in the diagnosis of ovarian carcinoma.
MATERIALS AND METHODS: Tissues from ovarian epithelial neoplasms diagnosed between 2004 and 2012 were tested using antibodies to WT1 and PAX8. The slides were assessed to determine levels of marker expression and related to ethnicity, ovarian tumour type, grade and stage.
RESULTS: Serous tumours were the main histological type (n = 44), the remaining being endometrioid (n = 15), mucinous (n = 15) and clear cell tumours (n = 7). Late stage at diagnosis was significantly associated with serous (p
Multiplex PCR for detection of Helicobacter pylori infection in gastric biopsies with lower inflammatory score

Fadilah N, Hanafiah A, Razlan H, Wong ZQ, Mohamed Rose I, Rahman MM

Br J Biomed Sci, 2016 Oct;73(4):180-187.
PMID: 27922429

BACKGROUND: No gold standard has yet been established for the diagnosis of H. pylori infection. A multiplex polymerase chain reaction (mPCR) was developed in this study for rapid, sensitive and specific detection of H. pylori from gastric biopsies.
METHODS: H. pylori infections were determined by in-house rapid urease test (iRUT), culture, histology and multiplex PCR.
RESULTS: A total of 140 (60.9%) from 230 patients were positive for H. pylori infection. H. pylori were detected in 9.6% (22/230), 17% (39/230), 12.6% (29/230) and 60% (138/230) of biopsy specimens by culture, iRUT, histology and mPCR, respectively. mPCR identified H. pylori infection in 100% of biopsies with positive histology and culture. All biopsies with positive iRUT yielded positive PCR except two cases. mPCR also detected H. pylori in additional 116, 101 and 109 biopsies that were negative by culture, iRUT and histology, respectively. Positive samples by mPCR showed lower average in H. pylori density, activity and inflammation scores. The Indians showed the highest prevalence of H. pylori infection compared to the Chinese and the Malays. In addition, Chinese patients with older age were significantly infected compared to other ethnicities.
CONCLUSION: PCR was able to detect the highest numbers of positive cases although the lowest average scores were recorded in the activity, inflammatory and H. pylori density.
Anaplastic lymphoma kinase (ALK) mutations in patients with adenocarcinoma of the lung

Mohamad N, Jayalakshmi P, Rhodes A, Liam CK, Tan JL, Yousoof S, et al.

Br J Biomed Sci, 2017 Oct;74(4):176-180.
PMID: 28705139 DOI: 10.1080/09674845.2017.1331520

BACKGROUND: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death. Approximately 2-16% of NSCLC patients with wild-type epidermal growth factor receptor (EGFR) harbour anaplastic lymphoma kinase (ALK) mutations. Both EGFR and ALK mutations occur most commonly in Asian patients with NSCLC. As targeted therapy is available for NSCLC patients with these mutations, it is important to establish reliable assays and testing strategies to identify those most likely to benefit from this therapy.
MATERIALS AND METHODS: Patients diagnosed with adenocarcinoma of the lung between 2010 and 2014 were tested for EGFR mutations. Of these, 92 cases were identified as EGFR wild type and suitable candidates for ALK testing utilising immunohistochemistry and the rabbit monoclonal antibody D5F3. The reliability of the IHC was confirmed by validating the results against those achieved by fluorescence in situ hybridisation (FISH) to detect ALK gene rearrangements.
RESULTS: Twelve (13%) cases were positive for ALK expression using immunohistochemistry. Of the 18 evaluable cases tested by FISH, there was 100% agreement with respect to ALK rearrangement/ALK expression between the assays, with 11 cases ALK negative and 7 cases ALK positive by both assays. ALK tumour expression was significantly more common in female compared to male patients (29.6% vs. 6.2%, P
Biomedical Science in Brief

Lotfy M, Badra G, Burham W, Alenzi FQ, Bermejo-Martin JF, Bernardo D, et al.

Br J Biomed Sci, 2006 Jan;63(4):171-184.
PMID: 28700882 DOI: 10.1080/09674845.2006.11732742
Fulltext Changes in Mitochondrial Epigenome in Type 2 Diabetes Mellitus

Low HC, Chilian WM, Ratnam W, Karupaiah T, Md Noh MF, Mansor F, et al.

Br J Biomed Sci, 2023;80:10884.
PMID: 36866104 DOI: 10.3389/bjbs.2023.10884

Type 2 Diabetes Mellitus is a major chronic metabolic disorder in public health. Due to mitochondria's indispensable role in the body, its dysfunction has been implicated in the development and progression of multiple diseases, including Type 2 Diabetes mellitus. Thus, factors that can regulate mitochondrial function, like mtDNA methylation, are of significant interest in managing T2DM. In this paper, the overview of epigenetics and the mechanism of nuclear and mitochondrial DNA methylation were briefly discussed, followed by other mitochondrial epigenetics. Subsequently, the association between mtDNA methylation with T2DM and the challenges of mtDNA methylation studies were also reviewed. This review will aid in understanding the impact of mtDNA methylation on T2DM and future advancements in T2DM treatment.