Methylation of miR-34a, miR-34b/c, miR-124-1 and miR-203 in Ph-negative myeloproliferative neoplasms

BACKGROUND: MicroRNA (miR) miR-34a, -34b/c, -124-1 and -203 are tumor suppressor miRs implicated in carcinogenesis. METHODS: We studied DNA methylation of these miRs in Philadelphia-negative (Ph-ve) myeloproliferative neoplasms (MPNs). Methylation-specific PCR (MSP), verified by direct sequencing of the methylated MSP products, was performed in cell lines, normal controls and diagnostic marrow samples of patients with MPNs. RESULTS: Methylation of these miRs was absent in the normal controls. miR-34b/c were homozygously methylated in HEL cells but heterozygously in MEG-01. In HEL cells, homozygous miR-34b/c methylation was associated with miR silencing, and 5-aza-2'-deoxycytidine treatment led to re-expression of both miR-34b and miR-34c, consistent with that both miRs are under the regulation of the same promoter CpG island. miR-34a was heterozygously methylated in MEG-01 and K-562. miR-203 was completely unmethylated in K-562 and SET-2 but no MSP amplification was found in both HEL and MEG-01, suggestive of miR deletion. In primary samples, four each had miR-34b/c and -203 methylation, in which two had concomitant methylation of miR-34b/c and -203. miR-34a was methylated in one patient and none had methylation of miR-124-1. Seven patients (15.6%) had methylation of at least one of the four miRs. miR methylation did not correlate with clinical parameters, disease complications or JAK2 V617F mutation. CONCLUSION: This is the first report of miR hypermethylation in MPNs. miR-203 hypermethylation is not specific to Ph+ve leukemias but also present in Ph-ve MPNs. miR-34b/c methylation was associated with reversible miR silencing. There was no correlation of miR methylation with clinical demographic data or outcome.published_or_final_versio

Methylation of TET2, CBL and CEBPA in Ph-negative myeloproliferative neoplasms

A loss-of-function mutation of TET2, CBL and CEBPA has been implicated in the pathogenesis or leukaemic transformation of myeloproliferative neoplasm. As tumour suppressor genes may potentially be inactivated by promoter hypermethylation, the authors studied the methylation status of these genes in three cell lines and diagnostic marrow samples from 45 patients with myeloproliferative neoplasm (MPN) (essential thrombocythaemia, N=34; polycythaemia vera, N=7 and primary myelofibrosis, N=4) by methylation-specific PCR. TET2 was heterozygously methylated in MEG-01 and K562 but completely unmethylated in HEL. On the other hand, both CBL and CEBPA were completely unmethylated in all three cell lines. In the primary marrow samples, methylation of TET2 occurred in two (5.9%) patients with essential thrombocythaemia (4.4% of all patients), both without JAK2 V617 mutation, but not in polycythaemia vera or primary myelofibrosis. There was no association between TET2 methylation with the type of MPN (p=0.713). Hypermethylation of CBL or CEBPA was not detected in any patients. In summary, methylation of TET2, CBL and CEBPA is infrequent in MPN at diagnosis. The role of methylation of these genes at the time of leukaemic transformation warrants further study.published_or_final_versio

A postgraduate diploma course in community geriatrics for primary care doctors: Experience of first three years

This paper describes the setting up of a postgraduate diploma course in Community Geriatrics for primary care physicians and the experience gained in its first three years of running. This study programme was set up in response to the rapidly rising elderly population in Hong Kong and the fact that most of the primary care doctors practising today had an inadequate undergraduate curriculum in the health care issues that are relevant to older people. The objectives of the Course are to improve the knowledge, skills and confidence of primary care physicians in the care of elderly people. It also emphasises the aspects of care that are unique to elderly people. The Course is delivered by different modes of learning: distance learning, face-to-face problem-orientated seminars and small group clinical teaching. Learning centres are established in different regional hospitals in Hong Kong in order to allow small group clinical teaching while, at the same time, reducing travelling time for the students. Information technology is also used to facilitate teaching and learning, as well as to encourage communication among teachers and students. The Course was oversubscribed for all its intakes in the first three years of running. Some graduates have taken on visiting medical officer positions at elderly homes.published_or_final_versio

Hyaluronic Acid Instillation Following Arthroscopic Anterior Cruciate Ligament Reconstruction: A Double-blinded, Randomised Controlled Study.

PURPOSE: To assess the effect of hyaluronic acid instillation after arthroscopic anterior cruciate ligament (ACL) reconstruction for improving pain, range of movement, and function of the knee. METHODS: 28 men and 4 women underwent arthroscopic ACL reconstruction for isolated ACL rupture (partial or complete) and instability after recreational sports injury 2 to 120 months earlier. They were randomised to undergo arthroscopic ACL reconstruction followed by intra-articular viscoseal instillation (13 men and 3 women) or arthroscopic ACL reconstruction alone (15 men and 1 woman). The knee injury osteoarthritis outcome score (for pain, symptoms, activities of daily living, sport and recreation function, and quality of life), range of movement, knee circumference, and analgesic use were assessed on days -1, 1, and 2, and weeks 2, 6 and 12. RESULTS: Patient demographics were similar at baseline. At postoperative days 1 and 2, all subscales of the knee injury osteoarthritis outcome score (except for quality of life) were significantly higher in the viscoseal group. At weeks 2, 6, and 12, improvement in both groups equalised. Knee swelling (change in knee circumference) was significantly less in the viscoseal group at days 1 and 2 (p=0.009 and p=0.038, respectively, Mann-Whitney U test). Only one patient in the viscoseal group had a limited range of movement. No patient developed any adverse reaction. CONCLUSION: Intra-articular viscoseal instillation improved pain control and swelling 2 days after arthroscopic ACL reconstruction.published_or_final_versio

Examination of square-wave modulated voltage dip restorer and its harmonics analysis

Author name used in this publication: S. L. HoAuthor name used in this publication: K. W. E. Cheng2006-2007 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Somatostatin in the treatment of acute pancreatitis: A prospective randomised controlled trial

A prospective study was carried out to evaluate the efficacy of somatostatin in the treatment of acute pancreatitis. Seventy one patients were randomised to control (h = 36), or to the somatostatin group (h = 35) who received somatostatin 100 μg/h after a 250 μg bolus for the first two days. The following were compared in the two groups on admission and two days later: laboratory tests of prognostic significance, severity of pancreatitis, and also morbidity and mortality. Of the nine laboratory tests compared, the white blood cell count, lactate dehydrogenase, and urea concentrations were significantly lower in the somatostatin group two days after admission. Severity of pancreatitis after hospitalisation increased in fewer patients given somatostatin (NS). There was a trend toward fewer complications, especially local, in the somatostatin group. Mortality in both groups was low. Somatostatin appeared to reduce the local complications of acute pancreatitis. A larger trial is necessary to show its beneficial effect conclusively.published_or_final_versio

Investigation of voltage dip restorer using square wave inverter

Author name used in this publication: K. W. E. ChengAuthor name used in this publication: S. L. HoAuthor name used in this publication: K. P. WongRefereed conference paper2004-2005 > Academic research: refereed > Refereed conference paperVersion of RecordPublishe

A gene signature based method for identifying subtypes and subtype-specific drivers in cancer with an application to medulloblastoma

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Both male and female identity influence variation in male signalling effort

Conclusion: Despite the plasticity in male courtship effort, courtship displays had the potential to reliably convey information about the male to mate-searching females. Our experiment therefore underscores the importance of addressing the different sources contributing to variation in the expression of sexually-selected traits.</p