PubMed Health⌕ Search

Biomedical subjects

P K Chan

Publications and source records attributed to P K Chan.

At least 19 recordsLinked to original sources
PubMed2000

Risk of influenza A (H5N1) infection among health care workers exposed to patients with influenza A (H5N1), Hong Kong.

The first outbreak of avian influenza A (H5N1) occurred among humans in Hong Kong in 1997. To estimate the risk of person-to-person transmission, a retrospective cohort study was conducted to compare the prevalence of H5N1 antibody among health care workers (HCWs) exposed to H5N1 case-patients with the prevalence among nonexposed HCWs. Information on H5N1 case-patient and poultry exposures and blood samples for H5N1-specific antibody testing were collected. Eight (3.7%) of 217 exposed and 2 (0.7%) of 309 nonexposed HCWs were H5N1 seropositive (P=.01). The difference remained significant after controlling for poultry exposure (P=.01). This study presents the first epidemiologic evidence that H5N1 viruses were transmitted from patients to HCWs. Human-to-human transmission of avian influenza may increase the chances for the emergence of a novel influenza virus with pandemic potential.

Adult↗
PubMed2000

Hepatitis B virus reactivation in patients undergoing cytotoxic chemotherapy for solid tumours: precore/core mutations may play an important role.

Reactivation of the hepatitis B virus (HBV) is a rare, but well described complication of cytotoxic chemotherapy that may result in hepatic failure. Patients who are chronic carriers of the HBV and who have a G to A mutation at nucleotide 1896 in the precore region may develop more severe liver disease, possibly because of rapid selection and enhanced replication ability of the mutant strain. Such mutant viruses have been implicated occasionally in chemotherapy induced reactivation of hepatitis B virus. In this report, 5 patients with solid tumours were identified to have developed severe hepatitis B virus related liver disease during treatment with cytotoxic agents (with dexamethasone as anti-emetic). All had clinical and serological evidence of reactivation of the HBV. Three patients developed icteric hepatitis; 2 fully recovered, and 1 had died from progressive metastatic disease while recovering from the reactivation. The other two died from progressive liver failure. Direct sequencing of the polymerase chain reaction (PCR) products of the precore (preC) and precore promoter region of the HBV-DNA was carried out on the patients' serum samples taken during the episode of reactivation. In each case, similar mutations (G to A) in nucleotide 1896 of the preC region were found, together with additional mutations in the preC promoter. The present findings suggest that reactivation involving a mutant hepatitis B virus may lead to liver failure, which is possibly more severe than that caused by wild type HBV, and can be triggered by cytotoxic chemotherapy, or the administration of corticosteroids. In Eastern Asia the HBV carriage rate in adults is high. HBV reactivation and severe liver disease during cytotoxic treatment may become a serious and common problem in this region as cytotoxic chemotherapy is more widely used. Patients should be screened routinely for HBsAg in endemic areas of chronic hepatitis B virus infection prior to receiving cytotoxic treatment. The possibility of HBV reactivation should be considered in patients developing liver dysfunction. Patients who are HBeAg negative/Anti-HBe positive, and are suspected to be having an HBV reactivation, should have HBV-DNA levels measured for confirmation as they may carry a mutant HBV.

Adult↗
PubMed1999

The N-terminal half of NPM dissociates from nucleoli of HeLa cells after anticancer drug treatments.

NPM (nucleophosmin/B23) is a nucleolar phosphoprotein abundant in tumor cells. It dissociates from nucleoli of cells after treatments with various anticancer drugs. To determine the domain of NPM responsible for nucleolar binding, the N- and C-terminal halves of NPM were fused to GFP (green fluorescent protein) and introduced into HeLa cells. The N-terminal half (aa 1-150) of NPM (GFP-NPM(N)) was found localized in the nucleoli. A stable transformant of GFP-NPM(N) in HeLa cells was prepared and tested for association to nucleoli after anticancer drug treatments. GFP-NPM(N) dissociates from nucleoli after treatments with daunomycin, actinomycin D, camptothecin, and toyocamycin. The dissociation is time- and dose-dependent, and correlates with the cytotoxicity induced by the drugs. These results indicate that a stable transformant of GFP-NPM(N) in HeLa cells may be useful for the screening of anticancer drugs.

Antineoplastic Agents↗
PubMed1999

Inhibitory postsynaptic currents of rat substantia nigra pars reticulata neurons: role of GABA receptors and GABA uptake.

Whole-cell patch-clamp recordings were made from substantia nigra pars reticulata neurons in midbrain slices of young rats to study the characteristics of spontaneous and evoked inhibitory postsynaptic currents and factors which govern their decay kinetics. In the presence of the glutamate receptor antagonists D, L-2-amino-5-phosphonopentanoic acid (20 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (20 microM), bicuculline-sensitive spontaneous inward inhibitory postsynaptic currents were often observed using high Cl(-) electrodes. Application of the selective GABA(B) receptor antagonist CGP55845A (2 microM) did not alter the half decay time of these inhibitory postsynaptic currents, which however was prolonged by the potent GABA uptake blocker tiagabine (1 microM). In addition, the frequencies and amplitudes of the inhibitory postsynaptic currents were significantly reduced by tiagabine but these effects were prevented by CGP55845A. Inhibitory postsynaptic currents with similar sensitivity to bicuculline could also be evoked intranigrally. Similar to the spontaneous currents, the decay time of evoked inhibitory postsynaptic currents was not affected by 2 microM CGP55845A. However, in the absence of CGP55845A, tiagabine shortened the IPSC decay time but had an opposite effect if CGP55845A was present. These data suggest that the spontaneous and evoked inhibitory postsynaptic currents recorded from substantia nigra pars reticulata neurons are mediated mainly by GABA(A) receptors. Uptake of GABA helps to terminate these currents. When the uptake mechanism is blocked, accumulation of GABA would lead to activation of presynaptic GABA(B) receptors and reduction in GABA release. The role of postsynaptic GABA(B) receptors in substantia nigra pars reticulata of young rats seems to be minimal.

Animals↗
PubMed1999

Monoclonal antibody to prostate cancer nuclear matrix protein (PRO:4-216) recognizes nucleophosmin/B23.

BACKGROUND: The nuclear protein B23, nucleophosmin, is an RNA-associated nucleolar phosphoprotein reported to be more abundant in malignant and growing cells than in normal nondividing cells. We examined the levels of B23 in fresh human prostate tissue and in five human prostate cancer cell lines with monoclonal antibodies (mAb) to nucleophosmin (alpha-B23) and to human prostate cancer nuclear matrix proteins (PRO:4-216). METHODS: mAb PRO:4-216 and mAb alpha-B23 were used for protein level detection. Nuclear matrix proteins (NMPs) were prepared from prostate tumor and five human prostate cancer cell lines: LNCaP, TSU, DU145, PC-3, and PPC-1. The NMPs were run on one-dimensional and two-dimensional (2D) electrophoresis gels for Western blot analysis with the two mAbs. Histologic sections from paraffin-embedded normal and cancerous prostate tissue were stained immunohistochemically with both mAbs. RESULTS: PRO:4-216 and B23 mAbs identified a 40-kD protein (pI approximately 5.0) by Western blot analysis in the human prostate cancer cell lines and on two-dimensional blots of human prostate cancer NMPs. Immunohistochemical staining demonstrated large punctate nuclear dots in most cancer nuclei, while staining of normal tissue was less intense or absent. Predominant reactivity was of epithelial nuclei, with some minor reactivity of stromal nuclei. Red blood cells (RBCs) and white blood cells (WBCs) were routinely negative. CONCLUSIONS: PRO:4-216, previously characterized as recognizing prostate cancer nuclear matrix proteins, recognized B23/nucleophosmin. PRO:4-216 and alpha-B23 showed intense immunohistochemical staining of B23/nucleophosmin in cancer nuclei compared to adjacent normal cells in paraffin-embedded prostate tissue. This preliminary study showed the potential of B23 as a tumor marker for human prostate cancer.

Antibodies, Monoclonal↗
PubMed1999

A study of correlation between NPM-translocation and apoptosis in cells induced by daunomycin.

Human leukemia K562 and HeLa cells were treated with daunomycin (DA) for 1-4 hr. With the indirect immunofluorescence technique, we observed that the nucleolar protein nucleophosmin/B23 (NPM) shifted its location from the nucleolus to the nucleoplasm (NPM-translocation). The degree of NPM-translocation was determined by the relative immunofluorescent intensity in the nucleoli vs the nucleoplasm (defined as localization index, LI). We found that NPM-translocation, as determined by the decrease of LI, correlates with cytotoxicity. The degrees of NPM-translocation, chromatin condensation, and DNA fragmentation in HeLa cells were determined after treatment with 0.1, 0.5 and 1 microg/mL DA for 1 hr. We found that NPM-translocation (LI < 2.5) was observed in cells during the treatment with 0.5 and 1 but not with 0.1 microg/mL DA. Also, cells treated with 1 microg/mL remained in an NPM-translocated state for a longer time (5-6 hr) than those cells treated with 0.5 microg/mL (1-2 hr). Cells treated with 0.5 and 1 microg/mL DA showed increased levels of chromatin condensation beginning at 5 hr after the drug treatment. The number of cells with condensed chromatin increased with both time and drug concentration. No cells with condensed chromatin were observed in samples treated with 0.1 microg/mL DA, which also showed no significant NPM-translocation. Similar results were observed for induction of DNA fragmentation. We found that the drug concentration required for induction of DNA fragmentation and chromatin condensation coincided with the drug concentration required for NPM-translocation. Taken together, these results indicate that NPM-translocation correlates with apoptosis induced by daunomycin.

Antibiotics, Antineoplastic↗
PubMed1999

Lamivudine in the treatment of hepatitis B virus reactivation during cytotoxic chemotherapy.

Hepatitis B virus (HBV) reactivation has been described in cancer patients who received cytotoxic/immunosuppressive therapy and may result in liver damage of varying degrees of severity. There is no known effective treatment. Lamivudine, a nucleoside analogue, has been found to suppress HBV replication and to improve histology in chronic carriers of hepatitis B virus. The outcome of lamivudine therapy (at doses of 100 or 150 mg/day) in eight patients who developed HBV reactivation while receiving cytotoxic chemotherapy is described. Each of the eight patients had >98% suppression of the pretreatment HBV DNA levels. Three of the five patients who were initially HBeAg positive underwent seroconversion. Five patients had normalization of liver function tests and improvement in clinical condition. However, one patient died of hepatic failure due to HBV-related submassive liver necrosis, and two died of widespread metastases (including liver) from the primary malignancies. It is concluded that early commencement, i.e., at the onset of HBV reactivation before severe hepatic decompensation, of lamivudine may be effective in the control of HBV reactivation during chemotherapy. In Hong Kong, where hepatitis B infection is endemic, we propose to screen all cancer patients for hepatitis B surface antigen before immunosuppressive/cytotoxic therapy, and to closely monitor liver function of those who are found to be HBsAg seropositive.

Adult↗
PubMed1999

Presence of human herpesviruses 6, 7, and 8 DNA sequences in normal brain tissue.

The three novel human herpesviruses (HHV) 6, 7, and 8 are predominantly, but not exclusively, lymphotropic. In an attempt to elucidate their neurotropism in vivo, viral DNA sequences present in fresh autopsy cortical brain tissues obtained from 84 consecutive Chinese subjects (mean age, 66.9 years; range, 21-98 years) were detected by a nested polymerase chain reaction. These patients were apparently immunocompetent and free of clinical signs of viral diseases. HHV-6 DNA was detected in 36 of 84 (42.9%) patients, and the DNA-positive and -negative groups did not show a significant difference in age or sex distribution. Of the 36 HHV-6 DNA-positive cases, 9 (25%) were variant A and 27 (75%) were variant B. In view of the lower prevalence of variant A than variant B in the adult population, the two variants may share a comparable neuroinvasive potential. HHV-7 and HHV-8 DNA were detected respectively in three and two patients. The low positive rates of HHV-7 and HHV-8 may represent a relatively lower neuroinvasive potential of the viruses. Alternatively, the localization of HHV-7 and HHV-8 may be more restricted and the sampled cortical tissues may not represent the most abundant site of persistence in the nervous system. The results provide molecular evidence of the presence of the three newly identified herpesviruses in brain tissue. The pathogenic role for HHV-7 and HHV-8, as with HHV-6, in neurological diseases should not be overlooked.

Adult↗
PubMed1999

Parvovirus B19 infection causing red cell aplasia in renal transplantation on tacrolimus.

Parvovirus B19 infection is known to cause chronic anemia in immunocompromised hosts, including organ transplant recipients. Most reported cases of parvovirus B19-associated aplastic anemia in renal transplant recipients responded to intravenous immunoglobulin (IVIG) infusion. Tacrolimus is of special interest; it was proposed to be associated with pure red cell aplasia (PRCA) on its own because resolution of anemia on withdrawal of tacrolimus was previously observed. Interaction between parvovirus B19 infection and tacrolimus has not been reported. We report a case of parvovirus B19-associated PRCA in a renal transplant recipient treated with tacrolimus who failed to clear the virus despite repeated courses of IVIG. She showed complete recovery promptly after tacrolimus was switched to cyclosporine A. A well-documented concomitant decrease in serum parvovirus DNA polymerase chain reaction titer was also observed. This shows another mechanism by which tacrolimus can aggravate PRCA because of impaired clearance of parvovirus B19 infection in transplant recipients. For those patients receiving tacrolimus who have parvovirus B19 infection with refractory anemia and who fail to recover with IVIG, replacement of tacrolimus with cyclosporine A can be considered.

Adult↗
PubMed1999

Epidemiology of respiratory syncytial virus infection among paediatric patients in Hong Kong: seasonality and disease impact.

In a 5-year retrospective survey of respiratory syncytial virus (RSV) infections among hospitalized children, 1340 cases were identified of which, 98.4% were children < 5 years old with a male:female ratio of 1.5: 1. Most cases occurred from April to September showing a significant positive correlation with temperature and relative humidity. Community-acquired infections accounted for 92.5% of the cases with a mean hospital stay of 5 days. The estimated annual incidence of RSV infection requiring hospitalization was 2.5/1000 children < 5 years old with a mortality of 0.15% among hospitalized cases. On average, 248 children were admitted each year to the 1400-bed acute regional hospital accounting for an expenditure of HK S1.94 ((approximately US +/-0.25) million for hospitalization costs which equates to an annual cost in excess of HK $6.67 (approximately US $0.86) million for the whole of Hong Kong. An RSV vaccine should be a priority.

Child, Preschool↗
PubMed1999

Rubella immune status among healthcare workers in the Department of Obstetrics and Gynaecology of a regional hospital in Hong Kong: the need for a vaccination policy.

Rubella infection in early pregnancy is associated with severe consequences in the developing fetus. In Hong Kong, 8-11% of women of child-bearing age are still susceptible to rubella infection. Therefore, rubella immune status of healthcare workers who may have contact with pregnant women is of particular concern. Rubella immunity of healthcare workers in a Department of Obstetrics and Gynaecology was analysed. In the one and a half years of study, 134 healthcare workers voluntarily submitted blood samples for immunity determination and 16.4% of them were susceptible to rubella infection. A substantial proportion of healthcare workers of childbearing age (14%) was negative for rubella antibody. Susceptible healthcare workers have a risk of acquiring and subsequently transmitting the potentially teratogenic rubella infection to their patients. There is a need to review the rubella immunization policy for healthcare workers in Hong Kong.

Adult↗
PubMed1999

Detection of human herpesviruses 6 and 7 genomic sequences in brain tumours.

BACKGROUND: Human herpesviruses 6 and 7 (HHV-6, HHV-7) are ubiquitous, with primary infection occurring early in life followed by persistence, which may involve neural tissue. While HHV-6 and HHV-7 are predominantly T lymphotropic, the extent of tissue tropism in persistent infection is not known. AIM: To investigate neuropersistence and the role of HHV-6 and HHV-7 in brain tumorigenesis. METHODS: Nested polymerase chain reaction was used to detect HHV-6 and HHV-7 genomic sequences in preparations of total DNA extracted from 98 formalin fixed, paraffin embedded primary brain tumours. HHV-6 detected was further characterized into variants A and B by restriction fragment length analysis. RESULTS: HHV-6 was detected in 8.2% of cases and HHV-7 in 14.3% (14/98). None of the positive samples contained both viruses. Among the eight HHV-6 positive tumours, three harboured variant A and five variant B. Four of the five ependymomas studied contained viral DNA. Otherwise, both HHV-6 and HHV-7 were present at similar low frequencies in most of the tumour types investigated. CONCLUSIONS: The findings do not support an aetiological role of HHV-6 and HHV-7 in primary brain tumour, but they suggest that HHV-6 and HHV-7 are neurotropic in vivo and that the central nervous system seems to be one of the reservoirs for persistent infection.

Adolescent↗
PubMed1999

The nucleolar phosphoprotein B23 redistributes in part to the spindle poles during mitosis.

B23 is a major phosphoprotein in the interphasic nucleolus where it is involved in the assembly of pre-ribosomes. Using several cultured animal cells, we report that, in addition to the known redistribution of the protein during mitosis, B23 also becomes associated with mitotic spindle poles starting from early prometaphase onwards. Colocalization of B23 with the protein NuMA (Nuclear Mitotic Apparatus protein) was studied in mitotic cells and taxol-arrested cells. During the onset of mitosis, we observed that a fraction of B23 associates with, and dissociates from, the poles later than NuMA. At metaphase, both proteins are colocalized at the poles. The polar redistribution of both B23 and NuMA is mediated by microtubules. In taxol-treated cells, B23 is associated with the microtubule minus ends in the center of mitotic asters together with NuMA. Association of B23 with microtubule minus ends of mitotic asters was further confirmed with an in vitro assay, where B23 was found by western blotting to co-sediment with taxol-induced microtubule asters formed in a mitotic cell extract. Immunolabeling demonstrated that B23 and NuMA were both present at the center of the asters. Furthermore, an additional hyperphosphorylated form of B23 appeared when microtubule asters formed and associated with the asters. Immunodepletion of B23 from the mitotic extract revealed that taxol-induced microtubule asters were still observed in B23-immunodepleted mitotic extract, indicating that the presence of B23 at the poles is unlikely to be essential for spindle formation or stabilisation.

Animals↗
PubMed1999

High prevalence of human papillomavirus type 58 in Chinese women with cervical cancer and precancerous lesions.

The prevalence of human papillomavirus (HPV) among 332 Hong Kong Chinese women with abnormal Papanicolaou smears were determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The overall HPV positive rate was 44.3% with 18.6% (16/86) for normal/inflamed cervices, 36.4% (32/88) for condyloma, 64.7% (33/51) for cervical intraepithelial neoplasia grade 1 (CIN 1), 37.9% (11/29) for CIN 2, 68.3 (41/60) for CIN 3, and 77.8% (14/18) for carcinoma. Double HPV infection was detected in 17 of the 147 positive samples, with a significantly higher proportion in patients with normal or inflamed cervices than those with CIN or carcinoma (31.3% vs 10.5%, P =.029). The six most commonly identified genotypes were HPV 16 (33.3%), HPV 58 (23.8%), HPV 11, 18, 31 (8.8% each), and HPV 33 (6.8%). The worldwide uncommon genotype HPV 58 was found to be the second most common genotype detected in patients with cervical carcinoma (6 of 18 patients). HPV 58 infection showed a significant association with CIN/carcinoma (odds ratio [OR] = 3.98; 95% confidence interval [CI] = 1.22-14.35) and a significant trend of increase in prevalence with increasing severity of cervical lesion (chi(2) = 5.84; P =.016). Among Hong Kong Chinese women with abnormal cervical cytology, the detection of HPV 58 carried a positive predictive value of 68.6% for a cervical lesion of CIN 1 or higher severity. The high prevalence of HPV 58 among Chinese women, particularly in patients with carcinoma, has an implication on the design of HPV detection methods and the development of vaccines.

Adolescent↗
PubMed1998

Occlusion of the presynaptic action of cannabinoids in rat substantia nigra pars reticulata by cadmium.

Whole-cell patch-clamp recordings were made from substantia nigra pars reticulata (SNR) neurones in rat midbrain slices to characterise the presynaptic action of cannabinoids on GABA neurotransmission and to study the involvement of calcium channels. The cannabinoid agonist WIN55212-2 at 10 microM reduced the amplitudes of GABA(A) receptor mediated spontaneous postsynaptic currents (IPSCs). This effect was fully reversed by the selective cannabinoid CB1 receptor antagonist SR141716A (20 microM). WIN55212-2 also caused a reduction in the evoked IPSC amplitude, which was associated with a significant increase in the paired pulse ratio over a 50 ms interval. In addition, the reduction in spontaneous IPSC amplitude by WIN55212-2 could be largely occluded by the presence of extracellular Cd2+ (200 microM). These observations suggest that cannabinoids exert a presynaptic inhibition on GABAergic transmission to SNR neurones via CB1 receptor, an action which involves inhibition of Cd2+-sensitive presynaptic Ca2+ channels.

Animals↗
PubMed1998

Differential expression of pre- and postsynaptic GABA(B) receptors in rat substantia nigra pars reticulata neurones.

Whole-cell recordings were made from substantia nigra pars reticulata in rat midbrain slices to study the functional expression of pre- and postsynaptic GABA(B) receptors in GABA output neurones. Baclofen (up to 300 microM) dose-dependently activated a weak current which was insensitive to tetrodotoxin and Ca2+-free solution but blocked by Ba2+ and 2-OH-saclofen. The maximum current activated by baclofen (30 microM) was 43.0 +/- 4.5 pA (n = 27), representing only 23% of that in dopamine neurones. Baclofen (1-30 microM) also reduced the frequency of the GABA(A) receptor-mediated miniature inhibitory postsynaptic currents while the distribution of their amplitudes was unaffected. This presynaptic effect of baclofen, prominent at a concentration as low as 1 microM, was sensitive to 2-OH-saclofen and occluded by Cd2+, but was unaffected by Ba2+. The results suggest a predominant role of the presynaptic GABA(B) receptors in substantia nigra pars reticulata. The relative abundance of pre- and postsynaptic GABA(B) receptor subtypes in this brain region may also be important in mediating the anticonvulsant effect of baclofen in rats.

Animals↗
PubMed1998

Presynaptic inhibition of GABAergic inputs to rat substantia nigra pars reticulata neurones by a cannabinoid agonist.

Whole-cell patch-clamp recordings were made from substantia nigra pars reticulata (SNR) neurones in rat midbrain slices to investigate the electrophysiological effects of cannabinoids. The cannabinoid receptor agonist WIN 55212-2 (10 microM) significantly reduced intranigrally evoked and spontaneous inhibitory post-synaptic currents (IPSCs) which were mediated by GABA(A) receptors. The postsynaptic current induced by bath application of GABA was not affected by the presence of WIN 55212-2. The actions of WIN 55212-2 were not mimicked by the inactive enantiomer WIN 55212-3. WIN 55212-2 also hyperpolarized the membrane of SNR neurones in a tetrodotoxin/0-Ca2+-insensitive manner. These data suggest that cannabinoids modulate the activity of SNR neurones by presynaptic inhibition of GABA inputs. They may also exert a direct post-synaptic inhibition on these neurones.

Animals↗