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Biomedical subjects

P W Ng

Publications and source records attributed to P W Ng.

At least 19 recordsLinked to original sources
PubMed2005

Impaired transcriptional upregulation of Parkin promoter variant under oxidative stress and proteasomal inhibition: clinical association.

We provided data to show that the transcriptional activity of wildtype -258T in the parkin promoter region was significantly higher than the -258G variant in human cell lines. The transcriptional activity of wildtype -258T was significantly increased under oxidative stress by hydrogen peroxide, but this was not observed for the -258G variant. The transcriptional upregulation was significantly higher for wildtype -258T compared to -258G variant at 0.1, 0.2 and 0.4 mM of hydrogen peroxide. Similar results were obtained when the cells were treated with a proteasome inhibitor, MG132.Furthermore, in a case control study involving 753 subjects, we demonstrated that the parkin promoter -258G variant was associated with an increased risk of sporadic Parkinson's disease (PD) in the elderly ethnic Chinese population. Our clinical and laboratory data provide corroborative evidence that some older individuals who have the -258G variant may have a higher risk of developing PD.

Age Factors↗
PubMed2004

Consensus statement on ischaemic stroke care in Hong Kong.

OBJECTIVE: To issue guidelines for the care of acute stroke in Hong Kong, with the target audience of all health care professionals who are involved in acute stroke care. PARTICIPANTS: The Hong Kong Neurological Society and the Hong Kong Stroke Society. EVIDENCE: The panel applied the 'rule of evidence' used by the United States Agency for Health Care Policy and Research. When there is insufficient evidence, the recommendation was based on customary practice and was circulated among the members and fellows of the two societies before coming to a consensus. CONSENSUS PROCESS: Group meetings were held in 2002 to review the literature about acute care for patients with ischaemic stroke and to issue a consensus statement with reference to the local health care system. Participants of the meetings were appointed by the councils of The Hong Kong Neurological Society and the Hong Kong Stroke Society. The draft statement was circulated among the members and fellows of the two societies for comments before it was finalized. CONCLUSIONS: Ischaemic stroke is a heavy health care burden to Hong Kong. The current consensus statement provides a framework to establish a multidisciplinary approach towards its acute management.

Aged↗
PubMed2002

Lack of association between CYP1A1 polymorphism and Parkinson's disease in a Chinese population.

Apart from very few families who have a direct cause from genetic mutation, causes of most Parkinson's disease (PD) remain unclear. Many allelic association studies on polymorphism of different candidate genes have been studied. Although these association studies do not imply a causal relationship, it does warrant further studies to elucidate the pathophysiologic significance. CYP1A1 polymorphisms have been reported to be associated with PD in a Japanese population sample. Since CYP1A1 transforms aromatic hydrocarbons into products that may be neurotoxic and perhaps lead to PD, we therefore undertook a study to look at the possible association of CYP1A1 polymorphism and PD in a Chinese population. Contrary to the Japanese result, we did not find any statistically significant difference between the PD group and the control group in our study with a bigger sample size.

Aged↗
PubMed2001

Genome-wide expression changes induced by HTLV-1 Tax: evidence for MLK-3 mixed lineage kinase involvement in Tax-mediated NF-kappaB activation.

The Tax protein of human T-lymphotropic virus type 1 (HTLV-1), an oncoprotein that transactivates viral and cellular genes, plays a key role in HTLV-1 replication and pathogenesis. We used cDNA microarrays to examine Tax-mediated transcriptional changes in the human Jurkat T-cell lines JPX-9 and JPX-M which express Tax and Tax-mutant protein, respectively, under the control of an inducible promoter. Approximately 300 of the over 2000 genes examined were differentially expressed in the presence of Tax. These genes were grouped according to their function and are discussed in the context of existing findings in the literature. There was strong agreement between our results and genes previously reported as being Tax-responsive. Genes that were differentially expressed in the presence of Tax included those related to apoptosis, the cell cycle and DNA repair, signaling factors, immune modulators, cytokines and growth factors, and adhesion molecules. Functionally, we provide evidence that one of these genes, the mixed-lineage kinase MLK-3, is involved in Tax-mediated NF-kappa-B signaling. Our current results provide additional insights into Tax-mediated signaling.

Apoptosis↗
PubMed2001

Clinical characteristics of adult epilepsy patients in the 1997 Hong Kong epilepsy registry.

OBJECTIVE: To study the clinical characteristics of 2952 patients with epilepsy who had received drug treatment from the neurology outpatient clinics of eight major hospitals in Hong Kong. METHODS: Retrospective review of outpatient records. RESULTS: 1601 (54.3%) males and 1351 (45.7%) females with a median age of 35.8 years (range, 10-94.8) were studied. Seizure types included generalized tonic-clonic in 80.7% of patients, complex partial in 28.3%, simple partial in 14.4%, atypical absence in 2.6% and myoclonic in 1.4%, and 30.4% of patients had more than one seizure type. EEG, CT brain, MRI brain and neuropsychological evaluation were obtained in 81.2%, 61.7%, 17.0% and 2.2% of patients, respectively. The etiology of epilepsy was cryptogenic in 59.9%, symptomatic in 35.1% and idiopathic in 3.9%; the commonest were intracranial infection, cerebral vascular disease, cranial trauma and perinatal insult. Phenytoin, carbamazepine and valproate were the most frequently used drugs and 25.9% of patients were taking more than two drugs. 48.3% of patients had active seizures in the past six months and 26.4% were considered to have unsatisfactory control of their epilepsy. Medical refractoriness of epilepsy was associated with a history of perinatal insult, intracranial infection, congenital brain malformation, intracranial neoplasm, cerebral vascular disease, hippocampal sclerosis, mental retardation and a history of status epilepticus (P < 0.05). CONCLUSION: In this local cohort of adult patients with epilepsy under specialist care, there were a considerable number of patients falling into the category of cryptogenic epilepsy. Risk factors associated with medical refractoriness are similar to previous studies.

Adolescent↗
PubMed2000

The alpha-synuclein gene and Parkinson disease in a Chinese population.

OBJECTIVE: To study the Ala53Thr and Ala30Pro mutations of the alpha-synuclein gene in a large number of Chinese patients with Parkinson disease (PD) as well as controls. METHODS: We recruited 183 Chinese patients with sporadic PD, 17 with younger-onset PD (onset age <50 years), and 7 with PD and a positive family history as well as 227 unaffected Chinese control subjects from the outpatient departments of 2 major hospitals in Hong Kong. All subjects were assessed for the the diagnosis of PD by a consultant neurologist or geriatrician. Subjects were interviewed with a standard questionnaire that also questioned for family history. Venous blood samples were obtained from the subjects and genomic DNA was extracted and studied for the presence of Ala53Thr mutation in exon 4 and Ala30Pro mutation in exon 3 of the alpha-synuclein gene using a polymerase chain reaction restriction fragment length polymorphism method. RESULTS: None of the Chinese PD patients or controls had either the Ala53Thr (exon 4) or Ala30Pro (exon 3) mutation of the alpha-synuclein gene. CONCLUSION: We failed to discover Ala53Thr or Ala30Pro mutations in a large number of Chinese patients with PD and control subjects, adding to the emerging consensus that variations in the alpha-synuclein gene are associated with PD in few families worldwide.

Alleles↗
PubMed2000

Fornix-based trabeculectomy with Wise's suture technique in Chinese patients.

OBJECTIVE: To assess the safety and efficacy of fornix-based trabeculectomy with Wise's suture technique in Chinese subjects. DESIGN: A retrospective noncomparative case series. PARTICIPANTS: Forty-eight eyes of 44 Chinese subjects that underwent fornix-based trabeculectomy combined with intraoperative 0.4 mg/ml mitomycin-C for 3 to 5 minutes were studied. INTERVENTION: Conjunctival wound closure of all eyes was with the Wise's technique using 9-0 nylon suture to prevent leakage at the corneolimbal interface. MAIN OUTCOME MEASURES: The success rate, with or without antiglaucoma medication, the complication rate, and the longevity of the drainage blebs were analyzed. RESULTS: At a mean follow-up period of 21.8 +/- 4.5 months, 75% (36 eyes) had postoperative intraocular pressure of 21 mmHg or less. Of these, 23 eyes (47.9%) required no antiglaucoma medication, 7 eyes (14.6%) required one medication, 3 eyes (6.3%) required two medications, and 3 eyes (6.3%) required three medications. Ten eyes (21%) had early wound leak. Two eyes (4.2%) required surgical repair. Two eyes (4%) had hypotonous maculopathy. No other major complications were encountered. CONCLUSIONS: Fornix-based trabeculectomy with adjunctive mitomycin-C using Wise's suture technique appears to be both safe and effective in Chinese subjects.

Antimetabolites, Antineoplastic↗
PubMed1999

Molecular cloning and characterization of two novel pro-apoptotic isoforms of caspase-10.

Caspase-10/a (Mch4) and caspase-10/b (FLICE2) are related death effector domain-containing cysteine aspartases presumed to be at or near the apex of apoptotic signaling pathways. We report the cloning and characterization of two novel proteins that are splice isoforms of the caspase-10 family. Caspase-10/c is a truncated protein that is essentially a prodomain-only form of the caspase that lacks proteolytic activity in vitro but efficiently induces the formation of perinuclear filamentous structures and cell death in vivo. Caspase-10/c mRNA is specifically up-regulated upon TNF stimulation, suggesting a potential role of this isoform in amplifying the apoptotic response to extracellular stimuli such as cytokines. Caspase-10/d is a hybrid of the known caspases Mch4 and FLICE2, as it is identical to FLICE2 except for the small (p12) catalytic subunit, which is identical to Mch4. Caspase-10/d is proteolytically active in vitro and also induces cell death in vivo, although it is less active than Mch4. The mRNAs for all known isoforms of caspase-10 are abundantly expressed in fetal lung, kidney, and skeletal muscle but are very poorly expressed or absent in these tissues in the adult, implying a possible role for the caspase-10 family in fetal development.

Amino Acid Sequence↗
PubMed1999

One-week ranitidine bismuth citrate versus colloidal bismuth subcitrate-based anti-Helicobacter triple therapy: a prospective randomized controlled trial.

OBJECTIVE: The efficacy of 1 wk bismuth triple therapy is adversely influenced by the presence of metronidazole resistance. In vitro studies suggest that ranitidine bismuth citrate (RBC) plus metronidazole exhibit synergistic activity against metronidazole resistant strains of Helicobacter pylori (H. pylori). Whether this confers a superior clinical efficacy remains unproven. This study compared the efficacy of RBC-based triple therapy with bismuth triple therapy in eradication of H. pylori. METHODS: Patients with H. pylori-related ulcer disease or gastritis were randomized to receive either 400/mg of RBC twice daily plus 400/mg of metronidazole and 500/mg of tetracycline four times daily for 1 wk (RMT) or 120/mg of colloidal bismuth subcitrate, 400/mg of metronidazole, and 500/mg of tetracycline, all given four times daily for 1 wk (BMT). Metronidazole susceptibility was determined by the E-test and pretreatment resistance was defined as minimum inhibitory concentration > or = 32/mg/L. RESULTS: Of 100 consecutive patients randomized, two patients were lost to follow-up in each group. Forty-three of 85 (51%) H. pylori isolates were metronidazole resistant. Per-protocol cure rate for RMT and BMT was 40 of 41 (98%) and 37 of 44 (84%), respectively (p = 0.058). Intent-to-treat cure rate for RMT and BMT was 46 of 50 and 41 of 50, respectively (92% vs 82%, p = 0.23). A significantly higher eradication of metronidazole resistant H. pylori was observed in the RMT group (25 of 25, 100%) than in the BMT group (12 of 16, 75%), (p = 0.018). Side effects observed in the two treatment groups were comparable. CONCLUSIONS: One week of RBC triple therapy with metronidazole and tetracycline is an effective anti-Helicobacter therapy. This regimen is more appropriate in areas of high prevalence of metronidazole resistance.

Adolescent↗
PubMed1998

Mutations which abolish phosphorylation of the TRAF-binding domain of TNF receptor 2 enhance receptor-mediated NF-kappa B activation.

We demonstrate that a 41 amino acid region (amino acids 379 to 419) in the cytoplasmic domain of tumor necrosis factor receptor 2 (TNFR2) is phosphorylated by unidentified kinase(s) both in vitro and in vivo. This domain (denoted x1c) corresponds almost exactly to the previously identified TRAF-binding domain and is by itself sufficient as a substrate for phosphorylation. In addition, the x1c domain is also crucial for TNFR2-mediated NF-kappa B activation. The cytoplasmic domain of TNFR2 lacks tyrosines, and conversion of all 12 potential serine and threonine phosphorylation targets in x1c to alanines either had no effect on NF-kappa B activation or resulted in enhanced NF-kappa B activity, depending on the structural context of x1c. The results show that while the TRAF-binding domain of TNFR2 is a major target of kinases, its phosphorylation is not required for NF-kappa B activation. Our data moreover suggest that phosphorylation of x1c negatively regulates the activation of NF-kappa B.

Amino Acid Sequence↗
PubMed1998

Genetic and environmental risk factors for Parkinson's disease in a Chinese population.

An epidemiological study of the environmental and genetic factors as well as the possible interplay between them was conducted among 215 patients with Parkinson's disease and 313 controls in a Chinese population in Hong Kong. In univariate analysis, a regular tea drinking habit was found to be a protective factor, which had not been reported before. Smoking (a protective factor), family history, duration of pesticide exposure (in years) in farming and pesticide exposure during farming in women (both risk factors) have been reported previously. In multivariate analysis, current smoking reached borderline significance at the 5% level and the variables, years exposed to pesticides and family history were significant at the 10% level. By contrast with the common occurrence of polymorphism of the CYP2D6 gene (a gene involved with xenobiotic metabolism) in white people, it is very rare in China and is not thought to be a significant factor contributing to Parkinson's disease in Chinese people.

Aged↗
PubMed1997

Anti-Helicobacter pylori treatment in bleeding ulcers: randomized controlled trial comparing 2-day versus 7-day bismuth quadruple therapy.

BACKGROUND: One-week bismuth triple therapy has been established to be highly effective in curing H. pylori infection, but patient compliance has been the major factor of success in therapy. For patients hospitalized for ulcer bleeding, an effective regimen that can completed before discharge will ensure full compliance. AIM: To compare 2-day versus 1-wk bismuth triple therapy plus omeprazole in curing H. pylori infection and bleeding peptic ulcers. METHODS: 100 patients with non-actively bleeding duodenal (DU) or gastric ulcers (GU) and confirmed H. pylori infection were randomized to receive either bismuth subcitrate 120 mg, tetracycline 500 mg, and metronidazole 400 mg four times daily for 1 wk (OBTM-7) or bismuth subcitrate 240 mg, tetracycline 500 mg, and metronidazole 400 mg four times daily for 2 days (OBTM-2). Both groups of patients also received omeprazole 20 mg twice daily for the first week. In the OBTM-2 group, the anti-Helicobacter therapy was finished during hospitalization. Endoscopy was repeated 5 wk after randomization to monitor ulcer healing and determine H. pylori status. Side effects related to the anti-Helicobacter therapy was graded as follows: A, mild discomfort, which did not affect daily activity; B, moderate discomfort affecting daily activity; and C, severe discomfort and patients discontinued therapy. RESULTS: Forty-six patients in the OBTM-2 group and 50 in the OBTM-7 group returned for follow-up endoscopy. With an intention-to-treat analysis, ulcer healing was achieved in 44 of 46 patients (95.7%) in the OBTM-2 group versus 49 of 50 (98%) in the OBTM-7 group, p = 0.61. H. pylori eradication was successful in 35 of 46 patients (76.1%) in the OBTM-2 and in all 50 patients (100%) in the OBTM-7 group, p = 0.00024. There was no difference in the severity of side effects experienced by the patients in the OBTM-2 group than in the OBTM-7 group (19 vs 32%, p = 0.16). None of the patients had rebled during the period of follow-up. CONCLUSION: Despite similar efficacy in ulcer healing, the 2-day quadruple therapy is less effective than the 1-wk regimen in curing H. pylori infection.

Activities of Daily Living↗
PubMed1994

Efficient and rapid affinity purification of proteins using recombinant fusion proteases.

In the affinity purification of recombinant fusion proteins, the rate-limiting step is usually the efficient proteolytic cleavage and removal of the affinity tail and the protease from the purified recombinant protein. We have developed a rapid, convenient and efficient method of affinity purification which can overcome this limitation. In one example of the method, the protease 3C from a picornavirus (3Cpro), which cleaves specific sequences containing a minimum of 6-7 amino acids, has been expressed as a fusion with glutathione S-transferase. The resultant recombinant 'fusion protease' cleaves fusion proteins bearing (from the amino-terminus) the same affinity tail as the fusion protease, a 3Cpro cleavage recognition site, and the recombinant protein of interest. The recombinant protein is purified in a single chromatographic step which removes both the affinity tail and the fusion protease. The advantages over existing methods include much improved specificity of proteolytic cleavage, complete removal of the protease and the affinity tail in one step, and the option of adding any desired amount of fusion protease to ensure efficient cleavage. The potential flexibility of the method is shown by the use of various affinity tails and alternative fusion proteases.

3C Viral Proteases↗