Research Articles (Haematology and Cell Biology)

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Open Access
A case study of GM maize gene flow in South Africa
(Springer, 2011) Viljoen, Chris; Chetty, Lukeshni
Background: South Africa has been growing first-generation commercial genetically modified (GM) maize since 1997. Despite a requirement for non-GM food, especially for export, there is no system for coexistence of GM and non-GM crop. Gene flow is a major contributor to commingling, and different distances of cross-pollination have been recorded for maize, using a variety of field-trial designs under different environmental conditions, with the furthest distance being 650 m. However, these trials have usually been small plots and not on the scale of commercial farming. There are also no published data regarding the extent of cross-pollination for maize in South Africa, even after a decade of commercialization of GM. Thus, the aim of this study, conducted from 2005 to 2007, was to determine the extent of GM maize cross-pollination under South African conditions in the context of commercial farming practice. Materials and methods: Field trials were planted with a central plot of yellow GM maize (0.0576 ha) surrounded by white non-GM maize (13.76 ha), in two different geographic regions over two seasons with temporal and spatial isolations to surrounding commercial maize planting. Cross-pollination from GM to non-GM maize was determined phenotypically across 16 directional transects. Pollen counts during flowering were compared to weather data as well as percentage cross-pollination. The data were transformed logarithmically, and mean percentage cross-pollination was compared to high cross-pollination. Results and discussion: Although there was a general congruency between wind data, pollen load and crosspollination, it is evident that wind data and pollen load do not solely explain the directional extent of crosspollination and that swirling winds may have contributed to this incongruence. Based on the logarithmic equations of cross-pollination over distance, 45 m is sufficient to minimize cross-pollination to between <1.0% and 0.1%, 145 m for <0.1% to 0.01% and 473 m for <0.01% to 0.001%. However, compared to this, a theoretical isolation distance of 135 m is required to ensure a minimum level of cross-pollination between <1.0% and 0.1%, 503 m for <0.1% to 0.01% and 1.8 km for <0.01% to 0.001% based on high values of cross-pollination. Conclusions: Based on the results of this study, the use of mean values of cross-pollination over distance may result in an underestimation of gene flow. Where stringent control of gene flow is required, for example, for non- GM seed production or for GM field trials under contained use, the high values of cross-pollination should be used to determine isolation distance. However, this may not be practical in terms of the isolation distance required. We therefore suggest that temporal and distance isolations be combined, taking into account the GM maize pollen sources within the radius of the most stringent isolation distance required.
Open Access
Chakalaka-induced vasodilatation in patients with chronic myeloid leukemia on tyrosine kinase inhibitors
(Health and Medical Publishing Group, 2009) Coetzee, J.; Louw, Vernon J.; Gartrell, Kevin; Viljoen, Chris D.
Open Access
Clinical haematology training in South Africa
(Health and Medical Publishing Group, 2010) Coetzee, M. J.
Abstract not available
Open Access
Cucurbitacin B inhibits growth, arrests the cell cycle, and potentiates antiproliferative efficacy of cisplatin in cutaneous squamous cell carcinoma cell lines
(Spandidos Publications, 2010) Chen, Weikai; Leiter, Amanda; Yin, Dong; Meiring, Muriel; Louw, Vernon J.; Koeffler, H. Phillip
Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer with a substantial risk of metastasis which causes clinical treatment failure. This study investigated the anti-CSCC effects of a triterpenoid compound, Cucurbitacin B (CuB). Dose-response studies showed that CuB inhibited 50% growth (ED50) of the CSCC cell lines (SRB1, SRB12, SCC13, COLO16) in liquid culture at 4x10-7 -10-5 M. Soft-agar assays demonstrated that nearly all of the CSCC clonogenic cells were inhibited at 10-7 M CuB. FACS analysis found that the compound (10-7 M, 48 h) caused G2/M arrest. The CSCC cells underwent profound morphologic changes within 60 min after exposure to CuB (10-7 M), rounding up and losing their pseudopodia. CuB (10-7 M) caused prominent multinucleation of the cells after they were pulse-exposed (24 h) to the drug, washed and cultured in normal medium for an additional 24 h. The drug (10-8-10-6 M, 3-24 h) decreased levels of CDC2 and cyclin B1 in SRB1 and SRB12 cell lines as seen by Western blot analysis. Migration of SRB1 and SRB12 cells was inhibited by 10-7 M CuB. Interestingly, CuB synergistically potentiated the anti-proliferative effect of cisplatin in CSCC. In summary, CuB has a prominent anti-proliferative activity on CSCC cells. In vivo studies and clinical trials of this drug should be pursued in CSCC.
Open Access
Differential sensitivity of von Willebrand factor (VWF) 'activity' assays to large and small VWF molecular weight forms: a cross-laboratory study comparing ristocetin cofactor, collagen-binding and mAb-based assays
(International Society on Thrombosis and Haemostasis, 2012) Favaloro, E. J.; Bonar, R.; Chapman, K.; Meiring, M.; Funk, D.
Background: von Willebrand disease (VWD), the most common inherited bleeding disorder, is caused by deficiencies and/or defects in von Willebrand factor (VWF). An effective diagnostic and VWD typing strategy requires plasma testing for factor VIII, and VWF antigen plus one or moreVWF'activity' assays. VWFactivity is classically assessed by using VWF ristocetin cofactor activity (VWF:RCo), although VWF collagen-binding (VWF:CB) and VWF mAbbased (VWF activity [VWF:Act]) assays are used by some laboratories. Objective: To perform a cross-laboratory study to specifically evaluate these three VWF activity assays for comparative sensitivity to loss of high molecular weight (HMW) VWF, representing the form of VWF that is most functionally active and that is absent in some types of VWD, namely 2A and 2B. Methods: A set of eight samples, including six selectively representing stepwise reduction in HMW VWF, were tested by 51 different laboratories using a variety of assays. Results: The combined data showed that the VWF:CB and VWF:RCo assays had higher sensitivity to the loss of HMW VWF than did the VWF:Act assay. Moreover, withinmethod analysis identified better HMW VWF sensitivity of some VWF:CB assays than of others, with all VWF:CB assays still showing better sensitivity than the VWF:Act assay. Differences were also identified between VWF:RCo methodologies on the basis of either platelet aggregometry or as performed on automated analyzers. Conclusions: We believe that these results have significant clinical implications for the diagnosis of VWD and monitoring of its therapy, as well as for the future diagnosis and therapy monitoring of thrombotic thrombocytopenic purpura.
Open Access
Laboratory diagnosis and management of von Willebrand disease in South Africa
(Thieme Medical Publishers, 2011) Meiring, Muriel; Coetzee, Marius; Kelderman, Mareli; Badenhorst, Philip
Patients with von Willebrand disease (VWD) in South Africa are cared for in 17 Hemophilia Treatment Centers. The exact prevalence of the disease is uncertain, but 539 patients are annotated in registries. VWD patients are mostly diagnosed in the five largest academic centers, and the classification of the subtypes is performed by one of these, the VWD testing facility. An algorithm is used for the diagnosis of VWD. The distribution of subtypes diagnosed by the VWD reference center is 38%, 58%, and 4% for type 1, 2, and 3, respectively, and ~15% of plasma samples received are rejected due to poor storage and transport conditions. A novel single nucleotide polymorphism has been found in an African patient with type 2B VWD. From the type 1 VWDpatients who were diagnosed by the VWD testing facility, 45% seem to have an increased VWF clearance phenotype with a propeptide-to-antigen ratio of 1.9±0.3. VWD patients are treated with desmopressin, factor (F)VIII/VWF concentrate (Haemosolvate FVIII; National Bioproducts Institute, Durban, South Africa), and tranexamic acid. Haemosolvate FVIII contains a VWF antigen concentration of 167±27 IU/mL, a ristocetin cofactor activity of 100±29 IU/mL, a collagen binding activity of 99±29 IU/mL, normal VWF multimers, and a FVIII concentration of 50 IU/mL. Not all patients with VWD are currently classified, and many VWD patients in South Africa are probably undiagnosed.
Open Access
Phase I, randomized, double-blind, placebo-controlled, single-dose escalation study of the recombinant factor VIIa variant BAY 86-6150 in hemophilia
(International Society on Thrombosis and Haemostasis, 2012) Mahlangu, J. N.; Coetzee, M. J.; Laffan, M.; Windyga, J.; Yee, T. T.; Schroeder, J.; Haaning, J.; Siegel, J. E.; Lemm, G.
Background: BAY 86-6150 is a new human recombinant factor VIIa variant developed for high procoagulant activity and longer action in people with hemophilia with inhibitors. Objectives: To investigate the safety, tolerability, pharmacodynamics, pharmacokinetics and immunogenicity of BAY 86-6150 in non-bleeding hemophilia subjects. Methods: The study included non-bleeding men (18–65 years of age)withmoderate or severe hemophilia AorBwith or without inhibitors. Sixteen subjects were randomized 3 : 1 to four cohorts of escalating doses of BAY 86-6150 (6.5, 20, 50 or 90 lg kg)1 [n = 3 per cohort]) or placebo (n = 1 per cohort); an independent data-monitoring committee reviewed previous cohort data before the next dose escalation. Blood samplingwas performed predose and postdose; subjects were monitored for 50 days postdose. Results: At the tested doses, BAY 86-6150 was not associated with clinically significant adverse events or dose-limiting toxicities. BAY 86-6150 pharmacokinetics exhibited a linear dose response, with a half-life of 5–7 h. Subjects demonstrated consistent, dose-dependent thrombin generation ex vivo in platelet-poor plasma (PPP) (mean peak effect, 26– 237 nMthrombin from 6.5 to 90 lg kg)1). Peak thrombin levels over time paralleled BAY 86-6150, with thrombin kinetics appearing to be slightly shorter; thus, circulating BAY 86-6150 retained activity. There were corresponding decreases in activated partial thromboplastin and prothrombin times. No subject developed de novo anti-BAY 86-6150 neutralizing antibodies during the 50-day follow-up. Conclusions: In this first-in-human, multicenter, randomized, double-blind, placebo- controlled, single-dose escalation study, BAY 86-6150 was tolerated at the highest dose (90 lg kg)1), with no safety concerns. Safety and efficacy will be further evaluated in phase II/III studies.
Open Access
Reducing unnecessary blood smear examinations: can Sysmex blood cell analysers help?
(The Society of Medical Laboratory Technologists, 2014-06) Joubert, J.; Weyers, R.; Raubenheimer, J.
Background: The microscopic assessment of a peripheral blood smear is an essential diagnostic tool. Many haematology laboratories currently assess smears microscopically for every full blood count request, many of which may however be assessed unnecessarily – an important consideration in resource-constrained settings. Modern blood cell analysers are increasing in sophistication and can flag abnormal specimens that may require microscopy. Objectives: To evaluate the flagging efficiency of the Sysmex haematology analysers and to determine whether this potentially labour-saving technology could assist in safely reducing the number of unnecessary microscopic blood smear assessments. Methods: A total of 427 full blood count specimens collected consecutively over a 24-hour period at NHLS Pelonomi and NHLS Kimberley, were evaluated microscopically and compared with the instruments' abilities to flag potential morphological abnormalities. Results: The Sysmex blood cell analysers flagged 63.7% of specimens as "positive" and 36.3% as "negative". After microscopy, false positive flags were found to constitute 18.5% and false negative flags 5.4% of the total number of smears reviewed, giving a total of 23.9% incorrect assessments. No false negative flag was clinically critical. Conclusion: False negative results occurring with the Sysmex instruments' flagging systems in our settings are relevant, although not critical. The potential time and monetary savings of a flagging-based smear review policy may weigh heavier than occasional false negatives. In the African milieu, where laboratories are faced with the challenges posed by staff- and other shortages, relying on instrumentation flagging to guide smear review policy should be considered.
Open Access
Screening for calreticulin mutations in a cohort of patients suspected of having a myeloproliferative neoplasm
(Health and Medical Publishing Group (HMPG), 2016) De Kock, A.; Booysen, C.
Background. The discovery of calreticulin (CALR) has shown it to be the second most frequent mutation after the Janus Kinase 2 (JAK2) mutation in myeloproliferative neoplasms (MPNs). Its structure indicates various functions, of which two are to ensure calcium homeostasis and proper folding of other target proteins. Over 36 types of CALR mutations have been identified, all causing a recurrent frameshift in the C-terminal domain affecting CALR’s localisation and calcium-binding function. Objective. To screen a cohort of 89 patients suspected of having an MPN for the CALR mutations. Methods. Capillary and gel electrophoresis were used in conjunction as confirmatory tests to screen the cohort of patients. Results. Of three samples containing a type 1 CALR mutation, two were heterozygous and one homozygous for a 52-base pair deletion in CALR. Conclusions. Most studies report CALR mutations to be present only in patients with primary myelofibrosis or essential thrombocythaemia, with mutual exclusivity to JAK2 mutations. The findings of this study indicate that JAK2 and CALR mutations are no longer considered mutually exclusive. Similarly, patients with a polycythaemia vera phenotype could also carry a CALR mutation.
Open Access
The use of topical crushed tranexamic acid tablets to control bleeding after dental surgery and from skin ulcers in haemophilia
(Wiley, 2007) Coetzee, M. J.

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