Biomedical subjects

M K Chan

Publications and source records attributed to M K Chan.

At least 19 recordsLinked to original sources

PubMed2006

Computed tomography-guided percutaneous radiofrequency ablation of osteoid osteoma: local experience.

Osteoid osteoma is a slow-growing tumour with limited growth potential. In the past, treatment comprised open surgery with en-bloc resection or curettage of the tumour. In recent years, various minimally invasive percutaneous treatments have gained popularity. We report on six patients who underwent computed tomography-guided percutaneous radiofrequency ablations of osteoid osteomas between January 2000 and December 2003 in a regional hospital in Hong Kong. Technical success was achieved in all procedures, with a mean follow-up of 40 months (range, 18-65 months). Five of the six patients achieved complete pain relief after the procedure and remained pain-free on subsequent follow-up. One patient with persistent symptoms after the first ablation was successfully treated with a second ablation. The mean in-hospital stay was 2.4 days. Progress in radiological healing was observed in all patients. There was one complication of skin burn over the needle entry site. Our experience shows that percutaneous computed tomography-guided radiofrequency ablation is a minimally invasive and cost-effective treatment for osteoid osteoma.

Adolescent↗

PubMed2006

Uterine fibroid embolisation in Chinese women: medium-term results.

OBJECTIVE: To evaluate the medium-term results of uterine fibroid embolisation in Chinese women with symptomatic uterine fibroids. DESIGN: Prospective case series study. SETTING: Gynaecology and Interventional Radiology units in a public hospital, Hong Kong. PATIENTS: Patients with symptomatic fibroids who underwent uterine fibroid embolisation in Queen Elizabeth Hospital from October 1998 to June 2004. RESULTS: Fifty women (mean age, 42.9 years; median follow-up period, 27.5 months) were recruited. Most (82%) had menorrhagia as the chief presenting symptom. Embolisation was successful in 49 (98%) women. Complications occurred in 12 (24%) patients, but were all self-limiting. Significant decrease in the median clinical uterine size (14 weeks vs 10 weeks) and median volume of the largest fibroid on magnetic resonance imaging (157.9 mL vs 45 mL) were observed during the first year. The reduction seemed to be maintained till the last follow-up. Menorrhagia improved in 34 (84%) patients, dysmenorrhoea in 28 (88%), pelvic pain in 18 (82%) and abdominal mass in 15 (83%). Poor response was found for urinary symptoms (29% improvement). Eight (16%) patients underwent hysterectomies after uterine fibroid embolisation. On logistic regression analysis, the only significant predictive factor for symptomatic improvement was fibroid volume reduction at 6 months (P=0.03). CONCLUSION: Uterine fibroid embolisation is an effective uterine-preserving therapy in patients with symptomatic fibroids; overall symptomatic improvement was estimated as 80%. Uterine or fibroid size reduction correlated well with clinical outcome. The impact of uterine fibroid embolisation on young women wishing to conceive is yet to be determined.

Adult↗

PubMed2005

Combined orbital irradiation and systemic steroids compared with systemic steroids alone in the management of moderate-to-severe Graves' ophthalmopathy: a preliminary study.

OBJECTIVE: To assess the efficacy and safety of combined orbital irradiation and systemic steroids in the management of moderate-to-severe Graves' ophthalmopathy. DESIGN: Single-blind randomised prospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: Sixteen patients with active moderate-to-severe Graves' ophthalmopathy who were randomly assigned to steroid therapy (ST group) or combination therapy of orbital irradiation and systemic steroids (SRT group) between June 2000 and June 2003. MAIN OUTCOME MEASURES: NOSPECS scoring system, total eye score, subjective eye score, and extra-ocular muscle thickness as determined by either computed tomographic or magnetic resonance imaging scans. RESULTS: The study was completed by 15 of 16 patients. Both groups experienced improvement in total eye score, soft tissue swelling, ocular motility, visual acuity, and subjective eye score at 52-week follow-up. Total eye score improved earlier in the SRT group, achieving statistical significance (P<0.05) at as early as 4 weeks of follow-up. Improvement in ocular parameters was greater and led to a significantly greater reduction in total eye score than in the ST group at weeks 16, 24, and 52. Maximum extra-ocular muscle thickness was significantly reduced in the SRT group only. No change was observed in proptosis in either group. No serious adverse effect was observed with the addition of orbital irradiation to steroid therapy. CONCLUSION: A combination of orbital irradiation and systemic steroids is well tolerated and more effective than steroids alone in the treatment of active moderate-to-severe Graves' ophthalmopathy. It achieves greater and more rapid improvement in soft tissue swelling, ocular motility, and visual acuity.

Administration, Oral↗

PubMed2002

Induction of a putative metallothionein gene in the blood cockle, Anadara granosa, exposed to cadmium.

The relationship between a putative metallothionein gene (MT) and exposure to cadmium (Cd) in blood cockles (Anadara granosa) is reported. In a 96-h dose-response experiment, mortality of cockles was found to proportionately increase in the range of 0.2-5.0 mg/l Cd with a calculated LC(50) of 2.94 mg/l. Exposure to 0.25 mg/l Cd for 16 days caused significant increases (P<0.05) in Cd concentrations in whole tissues, gills and hepatopancreas, and the accumulation of Cd in these tissues increased with the duration of exposure. Two cDNA libraries constructed using the hepatopancreas from control and Cd-treated cockles gave titres of 5.62 x 10(5) and 1.94 x 10(5) pfu/microg vector, respectively. A putative MT gene, AnaMT, of 510 nucleotides in length, was isolated from the treated cDNA library using a heterologous probe MT20 from the blue mussel, Mytilus edulis. Northern analyses using AnaMT as a probe indicated low expression of the MT mRNA in control animals. In cockles treated with 0.25 mg/l Cd for 4 days, MT mRNA level increased to approximately 168%, but declined to 108% at day 8. After 12 and 16 days of Cd treatment, expression of the MT gene was 138% and 187%, respectively, compared to the controls. These observations suggest that induction of the MT gene by a sublethal dose of Cd is rapid, occurring within 4 days of treatment.

Amino Acid Sequence↗

PubMed2002

Idiopathic myelofibrosis with extramedullary haemopoiesis involving the urinary bladder in a Chinese lady.

Extramedullary haemopoiesis (EMH) associated with idiopathic myelofibrosis most commonly involves the reticuloendothelial organs, such as the spleen and liver, although ectopic haemopoietic tissue has also been described rarely in the lymph nodes, skin, gastrointestinal tract, pleura, peritoneum, central nervous system, and genital and urinary tracts. We report on a 54-year-old Chinese lady with a long history of idiopathic myelofibrosis who presented with gross haematuria and left hydronephrosis due to EMH in the bladder trigone. Cystoscopic examination revealed a sessile necrotic papillary growth at the trigone, obstructing the left ureteric orifice. Transurethral resection of the bladder tumour was performed, and microscopic examination of the tumour chips demonstrated atypical megakaryocytes, immature granulocytes and normoblasts, confirming the presence of EMH. The residual bladder tumour responded well to low dose radiotherapy, with subsequent disappearance of haematuria and normalization of ultrasonogram findings.

Cell Lineage↗

PubMed2001

Chondroblastoma of the lumbar vertebra.

Chondroblastoma of the vertebra is a very rare condition. To our knowledge fewer than 20 cases have been reported in the world literature. We report a 54-year-old man with chondroblastoma of the fifth lumbar vertebra. The clinical and radiological aspects of the tumor are discussed, emphasizing the presence of an extraosseous mass suggestive of locally aggressive behavior.

Chondroblastoma↗

PubMed2001

Nodular fasciitis: MRI appearance and literature review.

OBJECTIVE: To describe the MRI features of nodular fasciitis and to review the clinical, MRI and histologic aspects of the tumor. DESIGN AND PATIENTS: Three patients with biopsy-proven nodular fasciitis were selected for a retrospective study. A literature review was also carried out. RESULTS AND CONCLUSIONS: All the lesions appeared slightly hyperintense to skeletal muscle on T1-weighted images, and hyperintense on T2-weighted images with fat saturation [either frequency saturation or Short TI Inversion Recovery (STIR) sequences]. Two enhanced homogeneously after intravenous gadolinium, whereas the third showed heterogeneous enhancement with a nonenhancing area. Despite the difference in enhancing patterns, the histologic appearances of these lesions were similar. Our study shows that the MRI appearance of nodular fasciitis may not be related to the location of lesion. It is thought that the age of nodular fasciitis may reflect its gross morphology, and it is possible that the MRI and histologic appearances could correlate with the age of the lesion, but it would require a larger series to evaluate this concept.

Adult↗

PubMed2001

Definitive identification of mammalian 5-hydroxymethyluracil DNA N-glycosylase activity as SMUG1.

Purification from calf thymus of a DNA N-glycosylase activity (HMUDG) that released 5-hydroxymethyluracil (5hmUra) from the DNA of Bacillus subtilis phage SPO1 was undertaken. Analysis of the most purified fraction by SDS-polyacrylamide gel electrophoresis revealed a multiplicity of protein species making it impossible to identify HMUDG by inspection. Therefore, we renatured the enzyme after SDS-polyacrylamide gel electrophoresis and assayed slices of the gel for DNA N-glycosylase activity directed against 5hmUra. Maximum enzymatic activity was identified between molecular mass markers 30 and 34 kDa. Protein was extracted from gel slices and subjected to tryptic digestion and analysis by mass spectrometry. Analysis revealed the presence of 11 peptides that were homologous or identical to the sequence of the recently characterized human single-stranded monofunctional uracil DNA N-glycosylase (hSMUG1). The cDNA of hSMUG1 was isolated and expressed as a recombinant glutathione S-transferase fusion protein that was shown to release 5hmUra with 20x the specific activity of the most purified bovine fraction. We conclude that hSMUG1 and HMUDG are the same protein.

Amino Acid Sequence↗

PubMed2001

Structural, magnetic and catalytic properties of a self-recognized mu-oxo-bridged diiron(III) bis(benzimidazole) complex.

The inherent nonplanarity and C(2) symmetry of the dimethyl-substituted bis(benzimidazole) ligand (Me(2)BBZ) results in two distinct atropisomers that, when separated, have been suggested to have potential for chiral recognition and catalysis. Here is reported the synthesis and characterization of a diiron mu-oxo-bridged bis(benzimidazole) complex, 1, that provides indirect support for this hypothesis. Dimerization of a racemic solution of iron-Me(2)BBZ monomers via the mu-oxo bridge yields (+,+) and (-,-) diastereomers whose complementary association can be attributed to the inherent sidedness of the metal-Me(2)BBZ interaction surface, and to the differences in the torsional angles of the phenyl(benzimidazole) units (34 degrees) and the Schiff base linkages (54 degrees). These results highlight the steric differences between the phenyl(benzimidazole) and Schiff-base portions of the ligand, features that could be important in the chiral recognition of ligands and in differentiating substrate trajectories as required for asymmetric catalysis. For completeness, studies of 1 in the catalytic epoxidation of styrene are also reported.

Journal Article↗

PubMed2001

Insight into the catalytic mechanism of DNA polymerase beta: structures of intermediate complexes.

The catalytic reaction mediated by DNA polymerases is known to require two Mg(II) ions, one associated with dNTP binding and the other involved in metal ion catalysis of the chemical step. Here we report a functional intermediate structure of a DNA polymerase with only one metal ion bound, the DNA polymerase beta-DNA template-primer-chromium(III).2'-deoxythymidine 5'-beta,gamma-methylenetriphosphate [Cr(III).dTMPPCP] complex, at 2.6 A resolution. The complex is distinct from the structures of other polymerase-DNA-ddNTP complexes in that the 3'-terminus of the primer has a free hydroxyl group. Hence, this structure represents a fully functional intermediate state. Support for this contention is provided by the observation of turnover in biochemical assays of crystallized protein as well as from the determination that soaking Pol beta crystals with Mn(II) ions leads to formation of the product complex, Pol beta-DNA-Cr(III).PCP, whose structure is also reported. An important feature of both structures is that the fingers subdomain is closed, similar to structures of other ternary complexes in which both metal ion sites are occupied. These results suggest that closing of the fingers subdomain is induced specifically by binding of the metal-dNTP complex prior to binding of the catalytic Mg(2+) ion. This has led us to reevaluate our previous evidence regarding the existence of a rate-limiting conformational change in Pol beta's reaction pathway. The results of stopped-flow studies suggest that there is no detectable rate-limiting conformational change step.

Animals↗

PubMed2001

Stimulation of human endonuclease III by Y box-binding protein 1 (DNA-binding protein B). Interaction between a base excision repair enzyme and a transcription factor.

Human endonuclease III (hNth1) is a DNA glycosylase/apurinic/apyrimidinic (AP) lyase that initiates base excision repair of pyrimidines modified by reactive oxygen species, ionizing, and ultraviolet radiation. Using duplex 2'-deoxyribose oligonucleotides containing an abasic (AP) site, a thymine glycol, or a 5-hydroxyuracil residue as substrates, we found the AP lyase activity of hNth1 was 7 times slower than its DNA glycosylase activity, similar to results reported for murine and human 8-oxoguanine-DNA glycosylase, which are also members of the endonuclease III family. This difference in rates contrasts with the equality of rates found in Escherichia coli and Saccharomyces cerevisiae endonuclease III homologs. A yeast two-hybrid screen for potential modulators of hNth1 activity revealed interaction with the damage-inducible transcription factor Y box-binding protein 1 (YB-1), also identified as DNA-binding protein B (DbpB). The in vitro addition of His(6)YB-1 to hNth1 increased the rate of DNA glycosylase and AP lyase activity. Analysis revealed that YB-1 affects the steady state equilibrium between the covalent hNth1-AP site Schiff base ES intermediate and the noncovalent ES intermediate containing the AP aldehydic sugar and the epsilon-amino group of the hNth1 active site lysine. This equilibrium may be a checkpoint in modulating hNth1 activity.

Base Pair Mismatch↗

PubMed2001

The use of brush cytology and directed biopsies for the detection of nasopharyngeal carcinoma and precursor lesions.

BACKGROUND: It has been proposed that nasopharyngeal carcinoma (NPC) has an early noninvasive stage, designated nasopharyngeal intraepithelial neoplasia (NPIN). Hence, the detection and treatment of NPIN will prevent NPC from developing, and this would be similar to the strategies used for cervical cancer prevention. We wanted to ascertain the feasibility of using a brush sampler to collect cells for the cytologic diagnosis of NPIN and NPC. If successful, the technique could be used as a screening test in endemic areas. METHODS: A disposable sampler (Uterobrush) was used to collect nasopharyngeal mucosal brushings from 546 patients for cytologic examination. After this, most patients had biopsies, and this allowed histologic-cytologic correlation to be undertaken. RESULTS: In 528 patients (96.7%) there were satisfactory cytologic and biopsy specimens for evaluation. There were 149 cases with positive histology and 103 had positive cytology (specificity was 100% and the sensitivity was 69.1%). One case of NPC with concurrent NPIN was seen among the biopsy specimens, but no case of NPIN was detected cytologically. CONCLUSIONS: The cytologic pickup of NPC was substantially lower than that obtained on biopsy. More importantly, NPIN was uncommon. Therefore, a screening test that depends on the collection of cells for the microscopic diagnosis of NPIN and NPC is unlikely to have a major impact on the incidence of NPC. Furthermore, obtaining a good cytologic specimen from the nasopharynx is not simple, and this further limits this technique for mass screening purposes. The concept of a cytologic test for NPC, similar to the Pap test for the prevention of uterine cervix cancer, has still to be realized.

Adult↗

PubMed2001

Neurologic injury after endovascular stent-graft and bilateral internal iliac artery embolization for infrarenal abdominal aortic aneurysm.

The authors report a rare neurologic complication after the implantation of a bifurcated stent-graft for abdominal aortic aneurysm. The stent-graft was extended to both external iliac arteries after embolization of both internal iliac arteries. The patient subsequently had weakness and numbness of both lower limbs with bowel and bladder incontinence. He probably had ischemic injury to the nerve roots or the lumbosacral plexus, which was related to extensive occlusion of their supplying arteries. The mechanism of spinal cord and neurologic ischemia after aortic stent-graft implantation is discussed.

Aged↗

PubMed2001

Recent advances in heme-protein sensors.

In recent years, an increasing number of proteins have been discovered which utilize heme cofactors to sense oxygen, carbon monoxide and nitric oxide. The identification and characterization of these proteins are revising our understanding of heme-mediated allostery first established in the early 1960s. Biochemical and structural studies are revealing new mechanisms for heme-driven conformational changes distinct from the classical hemoglobin model.

Allosteric Regulation↗

PubMed2001

Uterine artery embolisation for treatment of fibroids: experience in Chinese women.

Twelve women with symptomatic fibroids were treated with transcatheter uterine artery embolisation with the use of polyvinyl alcohol (PVA) particles. For the nine women who were due for follow-up, reduction in uterine volume and dominant fibroid size were observed on magnetic resonance imaging. All the nine women had normal luteinising hormone (LH) and follicle stimulating hormone (FSH) levels before the procedure and during the follow-up. Seven of the nine women reported noticeable symptomatic improvement during the follow-up. Pain experienced was of variable level, but well controlled. Adequate analgesia is essential for the procedure. Longer follow-up and prospective fertility studies are required to evaluate the long-term effects before this procedure could be safely extended to younger age groups.

Adult↗

PubMed2000

Synthesis and characterization of the dimethyl-substituted bisbenzimidazole ligand and its manganese complex.

Macrocycles with unique properties provide new avenues for the design of novel catalysts and materials. Here, we report, for the first time, the synthesis and characterization of the dimethyl-substituted bisbenzimidazole ligand (Me2BBZ) and its manganese complex (Mn-Me2BBZ). The Me2BBZ ligand is similar to porphyrin and phthalocyanine macrocycles in terms of its cavity size and metal-binding mode, but owing to electronic and charge differences, it exhibits properties that make it distinct from its structural counterparts. For instance, the optical spectra of bisbenzimidazoles lack transitions in the 500-900 nm region. Perhaps the most significant feature of the Me2BBZ ligand, however, is its inherent nonplanarity. Geometric restraints within this nonplanar ligand give rise to two atropisomers, which, when separated, could have potential in chiral catalysis and recognition. In addition, here we show that this nonplanarity can help to promote unusual crystal-packing interactions. Within the structure of the Mn-Me2BBZ complex, intermolecular pi-stacking interactions of the phenyl and benzimidazole groups lead to the formation of a distinct two-dimensional "staircase" lattice comprised of alternating Mn-Me2BBZ atropisomers. The potential significance of this structural arrangement is revealed by temperature-dependent magnetic studies that indicate weak antiferromagnetic coupling between the metal ions in the crystal. Fine-tuning of these long-range electronic and magnetic interactions could be useful for the design of novel molecular materials.

Journal Article↗

PubMed2000

New mechanistic insights from structural studies of the oxygen-sensing domain of Bradyrhizobium japonicum FixL.

The FixL heme domain serves as the dioxygen switch in the FixL/FixJ two-component system of Rhizobia. Recent structural studies of the Bradyrhizobium japonicum FixL heme domain (BjFixLH) have suggested an allosteric mechanism that is distinct from the classical hemoglobin model. To gain further insight into the FixL sensing mechanism, structures of BjFixLH bound to dioxygen, imidazole, and nitric oxide have been determined. These structures, particularly the structure of BjFixLH bound to its physiological ligand, dioxygen, have helped to address a number of important issues relevant to the BjFixLH sensing mechanism. On the basis of the oxy-BjFixLH structure, a conserved arginine is found to stabilize the dioxygen ligand in a mode reminiscent of the distal histidine in classical myoglobins and hemoglobins. The structure of BjFixLH bound to imidazole elucidates the structural requirements for accommodating sterically bulky ligands. Finally, the structure of BjFixLH bound to nitric oxide provides evidence for a structural intermediate in the heme-driven conformational change.

Animals↗

PubMed2000

Structural trends in first-row transition-metal bis(benzimidazole) complexes.

Dimethyl-substituted bis(benzimidazole) (Me2BBZ) is a novel macrocyclic ligand that possesses an intrinsic nonplanarity. To examine how metal-ion binding affects the magnitude of this nonplanarity, we have determined the structures of a periodic series of Me2BBZ complexes bound to Mn(II), Fe(II), Co(II), Ni(II), and Cu(II). These studies demonstrate that the extent of ligand ruffling and metal doming is indeed influenced by the nature of the metal. Concomitant with the periodic decrease of the ionic radii of the encapsulated divalent metal ion, a decrease in the magnitude of both the ligand nonplanarity and the metal out-of-the-plane distance is observed. For the metal out-of-the-plane distance, this correlation persists until the metal finally moves into the mean ligand plane. For the nonplanar distortion, the extent of the nonplanarity decreases to a limiting value that is intrinsic to the Me2BBZ ligand due to steric factors. These observations indicate that the relative sizes of the metal ion and the Me2BBZ ligand cavity have profound effects on the structural features of the metal-ligand complex.

Journal Article↗