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Long-Term Health Outcome and Quality of Life Post-HSCT for IL7Rα-, Artemis-, RAG1- and RAG2-Deficient Severe Combined Immunodeficiency: a Single Center Report

Abd Hamid IJ, Slatter MA, McKendrick F, Pearce MS, Gennery AR

J Clin Immunol, 2018 08;38(6):727-732.
PMID: 30105620 DOI: 10.1007/s10875-018-0540-9

Hematopoietic stem cell transplantation (HSCT) is curative for severe combined immunodeficiency (SCID), but data on long-term impact of pre-HSCT chemotherapy, immune reconstitution and quality of life (QoL) of specific SCID genotypes are limited. We evaluated the long-term immune-reconstitution, health outcome and QoL in IL7Rα SCID, Artemis and RAG1 and 2 SCID survivors > 2 years post-HSCT in our center. Clinical data and immune reconstitution parameters were collated, and patients/families answered PedsQL generic core scale v4.0 questionnaires. Thirty-nine patients with a diagnosis of IL7Rα SCID (17 patients), Artemis SCID (8 patients) and RAG1/2 SCID (13 patients) had undergone HSCT with median age at last follow up for IL7Rα SCID, 14 years (range 4-27) and Artemis and RAG1/2 SCID, 10 years (range 2-18). Many patients have ongoing medical issues at latest follow-up [IL7Rα (73%), Artemis (85%), RAG1/2 (55%)]. Artemis SCID patients experienced more sequela than RAG1/2 SCID. Conditioned recipients with Artemis and RAG SCID had more CD4+ naïve lymphocytes compared to unconditioned recipients. All patients except those of IL7Rα SCID reported lower QoL; further subset group analysis showed parents and Artemis and RAG1/2 survivors without ongoing medical issues reported normal QoL. Conditioned recipients have superior long-term thymopoiesis, chimerism and immunoglobulin-independence. QoL was normal in those who did not have medical issues at long-term follow-up.

Matched MeSH terms: DNA-Binding Proteins/deficiency*
Molecular investigation of Anaplasma spp. in domestic and wildlife animals in Peninsular Malaysia

Koh FX, Panchadcharam C, Sitam FT, Tay ST

Vet Parasitol Reg Stud Reports, 2018 08;13:141-147.
PMID: 31014863 DOI: 10.1016/j.vprsr.2018.05.006

Anaplasma spp. are Gram-negative obligate intracellular, tick-borne bacteria which are of medical and veterinary importance. Little information is available on Anaplasma infection affecting domestic and wildlife animals in Malaysia. This study investigated the presence of Anaplasma spp. in the blood samples of domestic and wildlife animals in Peninsular Malaysia, using polymerase chain reaction (EHR-PCR) assays targeting the 16S rRNA gene of Anaplasmataceae. High detection rates (60.7% and 59.0%, respectively) of Anaplasma DNA were noted in 224 cattle (Bos taurus) and 78 deer (77 Rusa timorensis and one Rusa unicolor) investigated in this study. Of the 60 amplified fragments obtained for sequence analysis, Anaplasma marginale was exclusively detected in cattle while Anaplasma platys/Anaplasma phagocytophilum was predominantly detected in the deer. Based on sequence analyses of the longer fragment of the 16S rRNA gene (approximately 1000 bp), the occurrence of A. marginale, Anaplasma capra and Candidatus Anaplasma camelii in cattle, Candidatus A. camelii in deer and Anaplasma bovis in a goat was identified in this study. To assess whether animals were infected with more than one species of Anaplasma, nested amplification of A. phagocytophilum, A. bovis and Ehrlichia chaffeensis DNA was performed for 33 animal samples initially screened positive for Anaplasmataceae. No amplification of E. chaffeensis DNA was obtained from animals investigated. BLAST analyses of the 16S rDNA sequences from three deer (R. timorensis), a buffalo (Bubalus bubalis) and a cow (B. taurus) reveal similarity with that of Candidatus Anaplasma boleense strain (GenBank accession no.: KX987335). Sequence analyses of the partial gene fragments of major surface protein (msp4) gene from two deer (R. timorensis) and a monitor lizard (Varanus salvator) show the detection of a strain highly similar (99%) to that of A. phagocytophilum strain ZJ-China (EU008082). The findings in this study show the occurrence of various Anaplasma species including those newly reported species in Malaysian domestic and wildlife animals. The role of these animals as reservoirs/maintenance hosts for Anaplasma infection are yet to be determined.

Matched MeSH terms: DNA, Bacterial/genetics
Fulltext Biosafety evaluation of culture-expanded human chondrocytes with growth factor cocktail: a preclinical study

Al-Masawa ME, Wan Kamarul Zaman WS, Chua KH

Sci Rep, 2020 12 09;10(1):21583.
PMID: 33299022 DOI: 10.1038/s41598-020-78395-y

The scarcity of chondrocytes is a major challenge for cartilage tissue engineering. Monolayer expansion is necessary to amplify the limited number of chondrocytes needed for clinical application. Growth factors are often added to improve monolayer culture conditions, promoting proliferation, and enhancing chondrogenesis. Limited knowledge on the biosafety of the cell products manipulated with growth factors in culture has driven this study to evaluate the impact of growth factor cocktail supplements in chondrocyte culture medium on chondrocyte genetic stability and tumorigenicity. The growth factors were basic fibroblast growth factor (b-FGF), transforming growth factor β2 (TGF β2), insulin-like growth factor 1 (IGF-1), insulin-transferrin-selenium (ITS), and platelet-derived growth factor (PD-GF). Nasal septal chondrocytes cultured in growth factor cocktail exhibited a significantly high proliferative capacity. Comet assay revealed no significant DNA damage. Flow cytometry showed chondrocytes were mostly at G0-G1 phase, exhibiting normal cell cycle profile with no aneuploidy. We observed a decreased tumour suppressor genes' expression (p53, p21, pRB) and no TP53 mutations or tumour formation after 6 months of implantation in nude mice. Our data suggest growth factor cocktail has a low risk of inducing genotoxic and tumorigenic effects on chondrocytes up to passage 6 with 16.6 population doublings. This preclinical tumorigenicity and genetic instability evaluation is crucial for further clinical works.

Matched MeSH terms: DNA Damage/drug effects
Lack of methylation on transgene leads to high level and persistent transgene expression in induced pluripotent stem cells

Alhaji SY, Nordin N, Ngai SC, Al Abbar A, Mei L, Abdullah S

Gene, 2020 Oct 20;758:144958.
PMID: 32683073 DOI: 10.1016/j.gene.2020.144958

Short-lived therapeutic gene expression in mammalian cells by DNA methylation is one of the major challenges in gene therapy. In this study, we assessed the implication of DNA methylation on the duration of GFP expression in mouse embryonic stem (ES) and mouse induced pluripotent stem (iPS) cells. The cells were transduced with lentivirus (LV) carrying green fluorescent protein (GFP) driven by either human elongation factor (EF1α) or cytomegalovirus (CMV) promoter. Transduced iPS cells exhibited higher percentage of GFP+ cells with persistent mean fluorescent intensity than transduced ES cells. Analysis on the integrated copy of transgene in the population of the transduced cells demonstrated similar copy number. However, significant increase in GFP intensity following 5-azaC treatment was observed in transduced ES cells only, suggesting the influence of DNA methylation in transgene silencing. Subsequent DNA methylation analysis showed that the promoter and the GFP region of the provirus in iPS cells had negligible methylation profile compared to transduced ES cells. Interestingly, sustained transgene expression was observed upon directed differentiation of transduced iPS cells towards CD34+ CD45+ cells. Hence, this study has shown that favourable transgene activity from lentiviral transduced iPS cells was due to the lack of methylation at the proviral regions.

Matched MeSH terms: DNA Methylation/genetics*
Fulltext DNA methylation mediates genotype and smoking interaction in the development of anti-citrullinated peptide antibody-positive rheumatoid arthritis

Meng W, Zhu Z, Jiang X, Too CL, Uebe S, Jagodic M, et al.

Arthritis Res Ther, 2017 03 29;19(1):71.
PMID: 28356135 DOI: 10.1186/s13075-017-1276-2

BACKGROUND: Multiple factors, including interactions between genetic and environmental risks, are important in susceptibility to rheumatoid arthritis (RA). However, the underlying mechanism is not fully understood. This study was undertaken to evaluate whether DNA methylation can mediate the interaction between genotype and smoking in the development of anti-citrullinated peptide antibody (ACPA)-positive RA.

METHODS: We investigated the gene-smoking interactions in DNA methylation using 393 individuals from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA). The interaction between rs6933349 and smoking in the risk of developing ACPA-positive RA was further evaluated in a larger portion of the EIRA (1119 controls and 944 ACPA-positive patients with RA), and in the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) (1556 controls and 792 ACPA-positive patients with RA). Finally, mediation analysis was performed to investigate whether DNA methylation of cg21325723 mediates this gene-environment interaction on the risk of developing of ACPA-positive RA.

RESULTS: We identified and replicated one significant gene-environment interaction between rs6933349 and smoking in DNA methylation of cg21325723. This gene-smoking interaction is a novel interaction in the risk of developing ACPA-positive in both Caucasian (multiplicative P value = 0.056; additive P value = 0.016) and Asian populations (multiplicative P value = 0.035; additive P value = 0.00027), and it is mediated through DNA methylation of cg21325723.

CONCLUSIONS: We showed that DNA methylation of cg21325723 can mediate the gene-environment interaction between rs6933349 and smoking, impacting the risk of developing ACPA-positive RA, thus being a potential regulator that integrates both internal genetic and external environmental risk factors.

Matched MeSH terms: DNA Methylation/genetics*
Fulltext Melatonin ameliorates the adverse effects of leptin on sperm

Almabhouh FA, Osman K, Ibrahim SF, Gupalo S, Gnanou J, Ibrahim E, et al.

Asian J Androl, 2016 10 18;19(6):647-654.
PMID: 27748315 DOI: 10.4103/1008-682X.183379

This study examined the effects of melatonin on leptin-induced changes in sperm parameters in adult rats. Five groups of Sprague-Dawley rats were treated with either leptin or leptin and melatonin or melatonin for 6 weeks. Leptin was given daily via the intraperitoneal route (60 μg kg-1 body weight) and melatonin was given in drinking water (10 mg kg-1 or 20 mg kg-1 body weight per day). Upon completion, sperm count, sperm morphology, 8-hydroxy-2-deoxyguanosine, Comet assay, TUNEL assay, gene expression profiles of antioxidant enzymes, respiratory chain reaction enzymes, DNA damage, and apoptosis genes were estimated. Data were analyzed using ANOVA. Sperm count was significantly lower whereas the fraction of sperm with abnormal morphology, the level of 8-hydroxy-2-deoxyguanosine, and sperm DNA fragmentation were significantly higher in rats treated with leptin only. Microarray analysis revealed significant upregulation of apoptosis-inducing factor, histone acetyl transferase, respiratory chain reaction enzyme, cell necrosis and DNA repair genes, and downregulation of antioxidant enzyme genes in leptin-treated rats. Real-time polymerase chain reaction showed significant decreases in glutathione peroxidase 1 expression with increases in the expression of apoptosis-inducing factor and histone acetyl transferase in leptin-treated rats. There was no change in the gene expression of caspase-3 (CASP-3). In conclusion, the adverse effects of leptin on sperm can be prevented by concurrent melatonin administration.

Matched MeSH terms: DNA Fragmentation/drug effects
Identification and functional analysis of variants in the human concentrative nucleoside transporter 2, hCNT2 (SLC28A2) in Chinese, Malays and Indians

Li L, Tan CM, Koo SH, Chong KT, Lee EJ

Pharmacogenet Genomics, 2007 Sep;17(9):783-6.
PMID: 17700367

The human concentrative nucleoside transporter (hCNT2), also known as SLC28A2, plays an important role in the cellular uptake across intestinal membrane of some naturally occurring nucleosides and nucleoside analogs. This study aims to determine the genetic variability of hCNT2 (SLC28A2) in three major Asian ethnic groups residing in Singapore: Chinese, Malay and Indian, and functionally characterize the variants of hCNT2. Healthy participants (n=96) from each group were screened for genetic variations in the exons of hCNT2 (SLC28A2) using denaturing high performance liquid chromatography and sequencing analyses. A total of 23 polymorphisms were identified in the exonic and flanking intronic regions, and ethnic differences in single nucleotide polymorphism frequencies were evident. Five novel nonsynonymous variants (L12R, R142H, E172D, E385K, M612T) were constructed by mutagenesis and functionally characterized in U-251 cells. Expression of these variants in U-251 cells revealed that all except E385K can uptake various substrates of hCNT2: inosine, ribavirin and uridine.

Matched MeSH terms: DNA Primers/genetics
Cardamonin from Alpinia rafflesiana inhibits inflammatory responses in IFN-γ/LPS-stimulated BV2 microglia via NF-κB signalling pathway

Chow YL, Lee KH, Vidyadaran S, Lajis NH, Akhtar MN, Israf DA, et al.

Int Immunopharmacol, 2012 Apr;12(4):657-65.
PMID: 22306767 DOI: 10.1016/j.intimp.2012.01.009

The increasing prevalence of neurodegenerative diseases has prompted investigation into innovative therapeutics over the last two decades. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the therapeutic choices to control and suppress the symptoms of neurodegenerative diseases. However, NSAIDs-associated gastropathy has hampered their long term usage despite their clinical advancement. On the natural end of the treatment spectrum, our group has shown that cardamonin (2',4'-dihydroxy-6'-methoxychalcone) isolated from Alpinia rafflesiana exerts potential anti-inflammatory activity in activated macrophages. Therefore, we further explored the anti-inflammatory property of cardamonin as well as its underlying mechanism of action in IFN-γ/LPS-stimulated microglial cells. In this investigation, cardamonin shows promising anti-inflammatory activity in microglial cell line BV2 by inhibiting the secretion of pro-inflammatory mediators including nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). The inhibition of NO and PGE(2) by cardamonin are resulted from the reduced expression of inducible nitric oxide synthase (iNOS) and cycloxygenase-2 (COX-2), respectively. Meanwhile the suppressive effects of cardamonin on TNF-α, IL-1β and IL-6 were demonstrated at both protein and mRNA levels, thus indicating the interference of upstream signal transduction pathway. Our results also validate that cardamonin interrupts nuclear factor-kappa B (NF-κB) signalling pathway via attenuation of NF-κB DNA binding activity. Interestingly, cardamonin also showed a consistent suppressive effect on the cell surface expression of CD14. Taken together, our experimental data provide mechanistic insights for the anti-inflammatory actions of cardamonin in BV2 and thus suggest a possible therapeutic application of cardamonin for targeting neuroinflammatory disorders.

Matched MeSH terms: DNA/immunology
Coxiella Detection in Ticks from Wildlife and Livestock in Malaysia

Khoo JJ, Lim FS, Chen F, Phoon WH, Khor CS, Pike BL, et al.

Vector Borne Zoonotic Dis, 2016 12;16(12):744-751.
PMID: 27763821

Recent studies have shown that ticks harbor Coxiella-like bacteria, which are potentially tick-specific endosymbionts. We recently described the detection of Coxiella-like bacteria and possibly Coxiella burnetii in ticks found from rural areas in Malaysia. In the present study, we collected ticks, including Haemaphysalis bispinosa, Haemaphysalis hystricis, Dermacentor compactus, Dermacentor steini, and Amblyomma sp. from wildlife and domesticated goats from four different locations in Malaysia. Coxiella 16s rRNA genomic sequences were detected by PCR in 89% of ticks tested. Similarity analysis and phylogenetic analyses of the 16s rRNA and rpoB partial sequences were performed for 10 representative samples selected based on the tick species, sex, and location. The findings here suggested the presence of C. burnetii in two samples, each from D. steini and H. hystricis. The sequences of both samples clustered with published C. burnetii sequences. The remaining eight tick samples were shown to harbor 16s rRNA sequences of Coxiella-like bacteria, which clustered phylogenetically according to the respective tick host species. The findings presented here added to the growing evidence of the association between Coxiella-like bacteria and ticks across species and geographical boundaries. The importance of C. burnetii found in ticks in Malaysia warrants further investigation.

Matched MeSH terms: DNA, Bacterial/genetics
Fulltext Shigella flexneri serotype 1c derived from serotype 1a by acquisition of gtrIC gene cluster via a bacteriophage

Tang SS, Carlin NI, Talukder KA, Cam PD, Verma NK

BMC Microbiol, 2016 Jun 27;16(1):127.
PMID: 27349637 DOI: 10.1186/s12866-016-0746-z

BACKGROUND: Shigella spp. are the primary causative agents of bacillary dysentery. Since its emergence in the late 1980s, the S. flexneri serotype 1c remains poorly understood, particularly with regard to its origin and genetic evolution. This article provides a molecular insight into this novel serotype and the gtrIC gene cluster that determines its unique immune recognition.
RESULTS: A PCR of the gtrIC cluster showed that serotype 1c isolates from different geographical origins were genetically conserved. An analysis of sequences flanking the gtrIC cluster revealed remnants of a prophage genome, in particular integrase and tRNA(Pro) genes. Meanwhile, Southern blot analyses on serotype 1c, 1a and 1b strains indicated that all the tested serotype 1c strains may have had a common origin that has since remained distinct from the closely related 1a and 1b serotypes. The identification of prophage genes upstream of the gtrIC cluster is consistent with the notion of bacteriophage-mediated integration of the gtrIC cluster into a pre-existing serotype.
CONCLUSIONS: This is the first study to show that serotype 1c isolates from different geographical origins share an identical pattern of genetic arrangement, suggesting that serotype 1c strains may have originated from a single parental strain. Analysis of the sequence around the gtrIC cluster revealed a new site for the integration of the serotype converting phages of S. flexneri. Understanding the origin of new pathogenic serotypes and the molecular basis of serotype conversion in S. flexneri would provide information for developing cross-reactive Shigella vaccines.

Matched MeSH terms: DNA, Bacterial/genetics*
Fulltext Germline mutation analysis of MLH1 and MSH2 in Malaysian Lynch syndrome patients

Zahary MN, Kaur G, Abu Hassan MR, Singh H, Naik VR, Ankathil R

World J Gastroenterol, 2012 Feb 28;18(8):814-20.
PMID: 22371642 DOI: 10.3748/wjg.v18.i8.814

To investigate the protein expression profile of mismatch repair (MMR) genes in suspected cases of Lynch syndrome and to characterize the associated germline mutations.

Matched MeSH terms: DNA Mutational Analysis; DNA Mismatch Repair
Fulltext XPC Lys939Gln polymorphism, smoking and risk of sporadic colorectal cancer among Malaysians

Ahmad Aizat AA, Siti Nurfatimah MS, Aminudin MM, Ankathil R

World J Gastroenterol, 2013 Jun 21;19(23):3623-8.
PMID: 23801864 DOI: 10.3748/wjg.v19.i23.3623

To investigate the risk association of xeroderma pigmentosum group C (XPC) Lys939Gln polymorphism alone and in combination with cigarette smoking on colorectal cancer (CRC) predisposition.

Matched MeSH terms: DNA-Binding Proteins/genetics*
Micromanipulation of culture niche permits long-term expansion of dental pulp stem cells--an economic and commercial angle

Govindasamy V, Ronald VS, Totey S, Din SB, Mustafa WM, Totey S, et al.

In Vitro Cell Dev Biol Anim, 2010 Oct;46(9):764-73.
PMID: 20725801 DOI: 10.1007/s11626-010-9332-0

Stem cells isolated from dental pulp possess the capacity for self-renewal and the potential for multi-lineage differentiation. However, dental pulp stem cells have different characteristics in terms of their culture conditions. The success of stem cells culture is governed by its micro-environmental niche. Therefore, we studied the effects of culture niche on long-term expansion of dental pulp stem cells in terms of cell morphology, growth kinetics, senescence pattern, cell surface marker expression differentiation capacity, and seeding plating density of dental pulp stem cells in four different, widely used media composition Among the various basal media tested, α-minimum essential media and knock out-minimum essential media supplemented with 10% fetal bovine serum were found to be the most optimal media composition in preserving the phenotypic characteristics and differentiation potential for prolonged periods as compared with DMEM-F12 and DMEM-LG. Plating density has been shown to affect overall yield. As a conclusion, the adoption of an appropriate culture system significantly improved cell yield, thus enabling the attainment of sufficient yields for therapeutic applications economizing in terms of cost of production and minimizing seeding cell density for maximum yield.

Matched MeSH terms: DNA Primers/genetics
Fenitrothion alters sperm characteristics in rats: ameliorating effects of palm oil tocotrienol-rich fraction

Taib IS, Budin SB, Ghazali AR, Jayusman PA, Mohamed J

Exp Anim, 2014;63(4):383-93.
PMID: 25030881

Exposure to organophosphate insecticides such as fenitrothion (FNT) in agriculture and public health has been reported to affect sperm quality. Antioxidants may have a potential to reduce spermatotoxic effects induced by organophosphate. The present study was carried out to evaluate the effects of palm oil tocotrienol-rich fraction (TRF) in reducing the detrimental effects occurring in spermatozoa of FNT-treated rats. Adult male Sprague-Dawley rats were divided into four equal groups: a control group and groups of rats treated orally with palm oil TRF (200 mg/kg), FNT (20 mg/kg) and palm oil TRF (200 mg/kg) combined with FNT (20 mg/kg). The sperm characteristics, DNA damage, superoxide dismutase (SOD) activity, and levels of reduced glutathione (GSH), malondialdehyde (MDA), and protein carbonyl (PC) were evaluated. Supplementation with TRF attenuated the detrimental effects of FNT by significantly increasing the sperm counts, motility, and viability and decreased the abnormal sperm morphology. The SOD activity and GSH level were significantly increased, whereas the MDA and PC levels were significantly decreased in the TRF+FNT group compared with the rats receiving FNT alone. TRF significantly decreased the DNA damage in the sperm of FNT-treated rats. A significant correlation between abnormal sperm morphology and DNA damage was found in all groups. TRF showed the potential to reduce the detrimental effects occurring in spermatozoa of FNT-treated rats.

Matched MeSH terms: DNA Damage/drug effects
An unusual mutation in RECQ4 gene leading to Rothmund-Thomson syndrome

Balraj P, Concannon P, Jamal R, Beghini A, Hoe TS, Khoo AS, et al.

Mutat Res, 2002 Oct 31;508(1-2):99-105.
PMID: 12379465

Rothmund-Thomson syndrome (OMIM #268400) is a severe autosomal recessive genodermatosis: characterised by growth retardation, hyperpigmentation and frequently accompanied by congenital bone defects, brittle hair and hypogonadism. Mutations in helicase RECQ4 gene are responsible for a subset of cases of RTS. Only six mutations have been reported, thus, far and each affecting the coding sequence or the splice junctions. We report the first homozygous mutation in RECQ4 helicase: 2746-2756-delTGGGCTGAGGC in IVS8 responsible for the severe phenotype associated with RTS in a Malaysian pedigree. We report also a 5321 G-->A transition in exon 17 and the updated list of the RECQ4 gene mutations.

Matched MeSH terms: DNA Helicases/genetics*
Quantitative analysis of fetal DNA in maternal plasma in gestational diabetes mellitus, iron deficiency anemia and gestational hypertension pregnancies

Zamanpoor M, Rosli R, Yazid MN, Husain Z, Nordin N, Thilakavathy K

J Matern Fetal Neonatal Med, 2013 Jul;26(10):960-6.
PMID: 23339569 DOI: 10.3109/14767058.2013.766710

OBJECTIVE: To quantify circulating fetal DNA (fDNA) levels in the second and third trimesters of normal healthy pregnant individuals and pregnant women with the following clinical conditions: gestational diabetes mellitus (GDM), iron deficiency anemia and gestational hypertension (GHT).
METHODS: The SRY gene located on the Y chromosome was used as a unique fetal marker. The fDNA was extracted from maternal plasma and the SRY gene concentrations were measured by quantitative real-time polymerase chain reaction (PCR) amplification using TaqMan dual labeled probe system.
RESULTS: No significant differences were observed in the mean fDNA concentration between normal and GDM pregnancy samples (p > 0.05) and also between normal and anemic pregnancy samples (p > 0.05) in both trimesters, but significant differences were observed between the third trimester normal and GHT pregnancy samples (p = 0.001). GDM and iron deficiency anemia do not affect the levels of fDNA in maternal plasma while GHT significantly elevates the levels of fDNA in maternal plasma.
CONCLUSIONS: Increased amount of circulating fDNA in maternal plasma could be used for early identification of adverse pregnancies. GDM and anemia do not affect the levels of fDNA in maternal plasma while GHT significantly elevates the levels of fDNA in maternal plasma. Hence, the elevated fDNA values could be used as a potential screening marker in pregnancies complicated with GHT but not with GDM and iron deficiency anemia.

Matched MeSH terms: DNA/blood*
Two new monofunctional platinum(II) dithiocarbamate complexes: phenanthriplatin-type axial protection, equatorial-axial conformational isomerism, and anticancer and DNA binding studies

Imran M, Rehman ZU, Hogarth G, Tocher DA, Chaudhry GE, Butler IS, et al.

Dalton Trans, 2020 Nov 10;49(43):15385-15396.
PMID: 33140800 DOI: 10.1039/d0dt03018j

The syntheses of two platinum(ii) dithiocarbamate complexes (1 and 2) that show quinoplatin- and phenanthriplatin-type axial protection of the Pt-plane are described. The Pt-plane of complex 2 is axially more protected than that of complex 1. Furthermore, both complexes adopt two different stereochemical conformations in the solid state (based on single-crystal X-ray structures) owing to the structurally flexible piperazine backbone; i.e., C-e,e-Anti (1) and C-e,a-Syn (2), where "C" stands for the chair configuration, "e" and "a" stand for the equatorial and axial positions and "Anti" (opposite side) and "Syn" (same side) represent the relative orientations in space of the terminal substituents on the piperazine ring. In complex 2, the C-e,a-Syn conformation may provide additional steric hindrance to the Pt-plane. Despite the lower lipophilicity of 2 as compared to that of 1, the in vitro anticancer action against selected cancer cell lines is better for the former revealing the superior role of the axial protection over lipophilicity in modulating anticancer activity. The activity against the cancer promoting protein NF-κB signifies that the mode of cancer cell death may be the result of hindering the activity of NF-κB in the initiation of apoptosis. The apoptotic mode of cell death has been established earlier in a study using Annexin V-FITC. Finally, DNA binding studies revealed that the complex-DNA adduct formation is spontaneous and the mode of interaction is non-intercalative (electrostatic/covalent).

Matched MeSH terms: DNA/metabolism*
Right atrial tuberculoma: a diagnosis too late

Ngow HA, Khairina WM

Cardiol J, 2011;18(5):560-3.
PMID: 21947994

Solitary intra-cardiac cavity tuberculoma is extremely rare and often only diagnosed during a post-mortem. We report a case of right atrial tuberculoma causing right atrial outflow tract obstruction in an immune-compromised man. The diagnosis of cardiac tuberculoma was made through the detection of mycobacterium tuberculosis DNA by tuberculosis-polymerase chain reaction in the pericardial fluid. The patient succumbed five days after admission but an autopsy was refused by his family.

Matched MeSH terms: DNA, Bacterial/analysis
Analytical performance of HPV assays on vaginal self-collected vs practitioner-collected cervical samples: the SCoPE study

Saville M, Hawkes D, Keung M, Ip E, Silvers J, Sultana F, et al.

J Clin Virol, 2020 06;127:104375.
PMID: 32361328 DOI: 10.1016/j.jcv.2020.104375

BACKGROUND: In the last decade, human papillomavirus (HPV) testing has been evaluated extensively for cervical screening, with studies finding increased sensitivity compared to cytology. Another advantage of HPV based-screening is the ability to test vaginal samples that can be collected by women themselves. Self-collection has the potential to extend cervical screening coverage by increasing participation rates, particularly among women who are under-screened or have never screened. This could have a significant impact on cervical cancer prevention, as the majority of invasive cervical cancer cases occur among under-screened women. Both the Netherlands and Australia have transitioned their national programs from cytology to HPV as the primary screening test and both countries include a pathway for self-collection.
OBJECTIVES: We evaluated the relative sensitivity for HPV detection of self-collection compared with practitioner-collected cervical specimens in the context of the Australian National Cervical Screening Program (NCSP).
STUDY DESIGN: 303 women aged ≥18 years attending a single tertiary referral centre took their own sample using a flocked-swab, and then had a practitioner-collected sample taken at colposcopy. All samples were tested at a single laboratory on the six PCR-based HPV assays which can be utilised in the NCSP; Roche cobas 4800 and cobas, Abbott RealTime, BD Onclarity, Cepheid Xpert, and Seegene Anyplex.
RESULTS: HPV16/18 results had high observed agreement between self- and practitioner-collected samples on all assays (range: 0.94-0.99), with good agreement for non-HPV16/18 oncogenic HPV types (range: 0.64-0.73).
CONCLUSIONS: Self-collection for HPV-based cervical screening shows good concordance and relative sensitivity when compared to practitionercollected samples across assays in the NCSP.

Matched MeSH terms: DNA, Viral/isolation & purification
Characterization of multidrug-resistant and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strains from Malaysian hospitals

Lim KT, Yeo CC, Md Yasin R, Balan G, Thong KL

J Med Microbiol, 2009 Nov;58(Pt 11):1463-1469.
PMID: 19589908 DOI: 10.1099/jmm.0.011114-0

The emergence of multidrug-resistant (MDR) and extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae poses a serious antibiotic management problem as resistance genes are easily transferred from one organism to another. Fifty-one strains of K. pneumoniae isolated from sporadic cases in various hospitals throughout Malaysia were analysed by antimicrobial susceptibility testing, PCR detection of ESBL-encoding genes and DNA fingerprinting. Although 27 of the 51 K. pneumoniae strains were MDR (i.e. resistant to three or more classes of antibiotics), the majority of the strains (98 %) were sensitive to imipenem. PCR detection using ESBL gene-specific primers showed that 46 of the K. pneumoniae strains harboured bla(SHV), 19 harboured bla(CTX-M), 5 harboured bla(OXA-1) and 4 harboured bla(TEM-1). Class 1 integron-encoded intI1 integrase was detected in 21 of the 51 K. pneumoniae strains and amplification of the integron 5'CS region showed the presence of several known antibiotic resistance gene cassettes of various sizes. Results of conjugation and transformation experiments indicated that some of the ESBL-encoding genes (i.e. bla(SHV), bla(CTX-M) and bla(TEM-1)) were transmissible and were likely plasmid-encoded. DNA fingerprinting using PFGE and PCR-based methods indicated that the 51 K. pneumoniae strains were genetically diverse and heterogeneous.

Matched MeSH terms: DNA Fingerprinting/methods

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