Comparison of haemoglobin H inclusion bodies with embryonic ζ globin in screening for α thalassaemia

Aims - To compare the haemoglobin (Hb) H inclusion test with immunocytochemical detection of embryonic ζ chains in screening for a thalassaemia. Methods - Blood samples from 115 patients with relevant clinical history and hypochromic microcytic indexes were screened using the HbH inclusion test and the Variant Hemoglobin Testing System (BioRad, Hercules, CA, USA). Results - The HbH inclusion test was positive in 61 of 115 cases, three of whom had HbH disease confirmed by electrophoresis. The remaining 58 had α thalassaemia 1. All three HbH cases and 56 of 58 cases of a thalassaemia 1 expressed embryonic ζ chains, giving a specificity of 96.7%. Fifty four of 115 cases had a negative HbH inclusion test, of whom 50 had β thalassaemia trait and three had iron deficiency. No diagnosis was reached for the remaining patient. Conclusion - The immunocytochemical test is as sensitive as the HbH inclusion test in screening for a thalassaemia. The presence of ζ chains is highly specific for a thalassaemia I incorporating the (--/SEA) deletion. The specificity and simplicity of the immunocytochemical test make it the test of choice in screening for α thalassaemia.published_or_final_versio

Comparison of the HbH inclusion test and a PCR test in routine screening for α thalassaemia in Hong Kong

Aim - To compare the haemoglobin (Hb) H inclusion test with a polymerase chain reaction CPCR) test in routine screening for or thalassaemia. Methods - Ninety nine peripheral blood samples from Chinese patients with mean corpuscular volume below 80fl were screened for a thalassaemia using the HbH inclusion test and by PCR utilising primers bridging the common deletion breakpoint of the South East Asian (--SEA/) deletion. Results - The HbH inclusion test was positive in 78 (79%) patients, 73 (93.7%) of whom carried the (--SEA/) deletion on analysis of their DNA by PCR, as did one patient with a negative HbH inclusion test. Conclusions - These results suggest that in areas with a high prevalence of the (--SEA/) deletion, such as Hong Kong, the HbH inclusion test can be replaced by PCR as the investigation of choice in screening for a thalassaemia.published_or_final_versio

Detection and characterisation of β-globin gene cluster deletions in Chinese using multiplex ligationdependent probe amplification

Background: Deletions in the β-globin cluster causing thalassaemia and hereditary persistence of fetal haemoglobin (HPFH) are uncommon and difficult to detect. Data in Chinese are very scarce. Aims: To use a recently available technique to investigate the frequencies and nature of β-globin cluster deletions in Chinese. Methods: 106 subjects with phenotypes of thalassaemia or HPFH and suspected to have deletions in the β-globin cluster were studied. A commercially available kit employing multiplex ligation-dependent probe amplification (MLPA) was used to screen for deletions. Gap PCR and direct nucleotide sequencing were used to characterise deletions detected. Results: 17 deletions in the β-globin cluster were found in 17 patients: 8 of Chinese (Aγδβ)0 thalassaemia, 7 of Southeast Asian (Vietnamese) deletion and 2 of Thai (Aγδβ) 0 thalassaemia. The only type of deletion detected in δβ-thalassaemia was Chinese (Aγδβ) 0 thalassaemia. The deletional form of HPFH was rarely seen in only 1 case of Thai (Aγδβ)0 thalassaemia. Deletions presenting as β-thalassaemia trait and raised HbF were all of the Southeast Asian (Vietnamese) deletion type. When these deletions were co-inherited with classical β-thalassaemia mutations in compound heterozygous states, the phenotypes could be very variable. Conclusions: In the Chinese population, there are only relatively few types of deletions seen in the β-globin cluster. MLPA is a fast and effective way of screening for these deletions. Characterisation of these deletions allows the development of simpler and more specific PCR-based tests for routine diagnostic use. Accurate prediction of phenotype is not always feasible. The molecular defects in many cases of HPFH still await discovery.published_or_final_versio

Identification and characterization of EBP, a novel EEN binding protein that inhibits Ras signaling and is recruited into the nucleus by the MLL-EEN fusion protein

The chimeric MLL-EEN fusion protein is created as a result of chromosomal translocation t(11;19)(q23;p13). EEN, an Src homology 3 (SH3) domain-containing protein in the endophilin family, has been implicated in endocytosis, although little is known about its role in leukemogenesis mediated by the MLL-EEN fusion protein. In this study, we have identified and characterized EBP, a novel EEN binding protein that interacts with the SH3 domain of EEN through a proline-rich motif PPERP. EBP is a ubiquitous protein that is normally expressed in the cytoplasm but is recruited to the nucleus by MLL-EEN with a punctate localization pattern characteristic of the MLL chimeric proteins. EBP interacts simultaneously with EEN and Sos, a guanine-nucleotide exchange factor for Ras. Coexpressoin of EBP with EEN leads to suppression of Ras-induced cellular transformation and Ras-mediated activation of Elk-1. Taken together, our findings suggest a new mechanism for MLL-EEN-mediated leukemogenesis in which MLL-EEN interferes with the Ras-suppressing activities of EBP through direct interaction. © 2004 by The American Society of Hematology.postprin

A dual colour dual fusion fluorescence in situ hybridisation study on the genesis of complex variant translocations in chronic myelogenous leukaemia

Complex variant 9;22 translocations occur in a significant minority of chronic myelogenous leukaemia (CML) patients. Different mechanisms of their formation have been described. We report dual colour dual fusion fluorescence in situ hybridisation data in 12 Chinese CML patients with complex translocations. Three previously reported breakpoint hotspots in a third partner chromosome (14q32, 17q25, 1q2l) were observed. In 10/12 (83.3%) patients, the abnormality occurred as a single step 3-break event. Only a single abnormal clone harbouring the complex translocation was seen in this group. The remaining 2 cases in the chronic phase showed a 4-break mechanism (2/12,16.7%). Deletion of 5' ABL at der(9) was not observed in any of the 12 patients, however, the loss of 3' BCR was observed in 1 patient (1/12, 8.3%). Together with previous findings, these data suggest that these variant translocations occur more often as a 3-break single-step process with no reciprocal ABL-BCR fusion. On the other hand, a 4-break event is also regularly seen during the initial stages of leukaemogenesis, which likely predisposes to der(9) deletion. The observed difference in rates of der(9) deletion reported in a series of CML patients with variant translocations may be related to a difference in rates of a 4-break event.published_or_final_versio

The effect of magnetic nanoparticles on the morphology, ferroelectric, and magnetoelectric behaviors of CFO/P(VDF-TrFE) 0–3 nanocomposites

Author name used in this publication: J. X. ZhangAuthor name used in this publication: J. Y. DaiAuthor name used in this publication: C. L. SunAuthor name used in this publication: C. Y. LoAuthor name used in this publication: S. W. OrAuthor name used in this publication: H. L. W. Chan2008-2009 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Common association of haemolytic uraemic syndrome with invasive Streptococcus pneumoniae infection in five Chinese paediatric patients

Haemolytic uraemic syndrome is an important cause of acute renal impairment in childhood. We review the incidence, and clinical and laboratory features of haemolytic uraemic syndrome in a Chinese population. Five patients were identified from 2006 to 2008. All patients were young children with associated invasive Streptococcus pneumoniae pulmonary infection. Serotypes 3, 14, and 19A were confirmed in four patients. The classical post-diarrhoeal form associated with Escherichia coli (O157:H7) infection was not seen. One patient died of acute respiratory failure. Streptococcus pneumoniae infection, as an associated condition in haemolytic uraemic syndrome, is important and relatively common in Chinese patients, especially among children. The acute clinical picture is similar to that reported in the western literature, except for an uncommon association with meningitis. The medium-term renal outcome of the Chinese population appears to be more favourable than the Caucasians. Widespread vaccination against Streptococcus pneumoniae may have resulted in changes in bacterial epidemiology and clinicians should be continuously aware of this severe disease. The use of washed blood components for transfusion in the acute stage requires further study.published_or_final_versio

Buried Thermoplastic Layer Diagnostics by the Use of Photo-Thermo-Acoustic Radiometry

Nondestructive evaluation of buried layers finds important applications in industry. In this paper we describe a fast, non-contact photothermal technique for thermoacoustic characterization of a thermoplastic layer sandwiched between two metal foils used in heat sealed food containers. For this particular application a non-contact measurement was required of the thickness of the polymer layer between two layers of aluminum in a heat sealed container rim at a speed of four locations of the container in 60 sec

Targeting aberrant epigenetic networks mediated by PRMT1 and KDM4C in acute myeloid leukemia

SummaryTranscriptional deregulation plays a major role in acute myeloid leukemia, and therefore identification of epigenetic modifying enzymes essential for the maintenance of oncogenic transcription programs holds the key to better understanding of the biology and designing effective therapeutic strategies for the disease. Here we provide experimental evidence for the functional involvement and therapeutic potential of targeting PRMT1, an H4R3 methyltransferase, in various MLL and non-MLL leukemias. PRMT1 is necessary but not sufficient for leukemic transformation, which requires co-recruitment of KDM4C, an H3K9 demethylase, by chimeric transcription factors to mediate epigenetic reprogramming. Pharmacological inhibition of KDM4C/PRMT1 suppresses transcription and transformation ability of MLL fusions and MOZ-TIF2, revealing a tractable aberrant epigenetic circuitry mediated by KDM4C and PRMT1 in acute leukemia

Gastrointestinal helminths in calves and cows in an organic milk production system

The main aim of this study was to determine the distribution of populations of gastrointestinal helminths in lactating crossbred cows and calves during the grazing season in an organic milk production system. In addition, the potential importance of the peripartum in relation to the parasite load was examined. Between January 2007 and December 2008, parasitological fecal examinations were performed on cattle belonging to the Integrated Animal Production Program of Embrapa Agrobiology. The cows' parasite load remained low during the study period, and there were no statistical differences (p > 0.05) in comparisons between the seasons. The average egg count showed a positive correlation (0.80) with the peripartum, such that egg elimination per gram (p < 0.05) was higher during the week of labor than during the pre and postpartum periods. Calves showed low parasite loads, with significantly higher egg elimination (p < 0.05) during the winter. The study indicated that infection with gastrointestinal helminths was not a limiting factor for milk production in the organic system. Specifically, it was concluded that the nematode load can be maintained at moderate levels throughout the production system, even in the absence of anthelmintic treatment