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Biomedical subjects

W H Sun

Publications and source records attributed to W H Sun.

At least 19 recordsLinked to original sources
PubMed2005

Surgical intervention for benign prostatic hyperplasia in Hong Kong.

OBJECTIVES: To review the treatment of benign prostatic hyperplasia in Hong Kong. DESIGN: Questionnaire study and review of previous presentations at the Hong Kong Urological Association meetings. SETTING: Urology centres in the public sector, Hong Kong. PARTICIPANTS: Thirteen public urology centres replied to the questionnaire survey. Thirty-two papers on benign prostatic hyperplasia presented at past annual scientific meetings of the Hong Kong Urological Association were identified. This would provide an overview of the development of surgical interventions for the treatment of benign prostatic hyperplasia carried out in Hong Kong. RESULTS: Most known surgical techniques have been practised in Hong Kong. Many 'minimally invasive procedures' have now fallen out of favour. Some newer techniques are now available and have produced favourable results. Nonetheless, transurethral resection of the prostate remains the standard surgical intervention in 12 of 13 centres in Hong Kong. CONCLUSION: Transurethral resection of the prostate remains the technique of choice for the treatment of benign prostatic hyperplasia in Hong Kong. New techniques should be comprehensively studied and evaluated before being introduced into regular practice.

Humans↗
PubMed2004

Low dose BCG as adjuvant therapy for superficial bladder cancer and literature review.

BACKGROUND: Bacillus Calmette-Guerin (BCG) at low doses has long been employed as prophylactic and therapeutic treatment for superficial cancer of the urinary bladder, aiming at reducing toxicity while maintaining efficacy. A retrospective review was reported, together with a review of the literature with respect to a low dose BCG regimen. METHODS: Forty-five consecutive patients with superficial bladder cancer (Ta or T1) with one or more of the appropriate criteria (grade above 1, stage above a, size >1 cm, multiple or recurrent), after complete transurethral resection, received 27 mg Connaught strain BCG weekly for 6 weeks. There was no maintenance therapy. Patients were evaluated with urine cytology and cystoscopy. Recurrence, progression and death were analysed. RESULTS: With a median follow up of 14 (range 3-61) months, 24 (53%) of the 45 patients responded to one course of 6 weekly BCG without recurrence. A further group of 13 (29%) patients responded to a second course of BCG on recurrence. Disease progressed in one (2.2%) patient. Two (4.4%) patients died of an unrelated condition. There was no disease specific mortality. Side-effects were common but well tolerated, with only two (4.4%) cases of treatment interruption. CONCLUSIONS: Low dose BCG could be an alternative option of adjuvant therapy for superficial bladder cancer with acceptable toxicity and good compliance.

Adjuvants, Immunologic↗
PubMed2001

Suppression of zeaxanthin formation does not reduce photosynthesis and growth of transgenic tobacco under field conditions.

Tobacco (Nicotiana tabacum cv. Xanthi) transformed with an antisense cDNA construct of violaxanthin de-epoxidase (VDE) was examined for the effects of suppressed xanthophyll-cycle activity on photoinhibition, photosynthesis and growth under field conditions. De-epoxidation of violaxanthin and non-photochemical quenching were highly inhibited in antisense plants relative to vector-control and wild-type plants. However, no differences were observed between antisense and control plants in photosynthetic CO(2) uptake and maximum photochemical yield [(F(m)-F(o))/F(m)] measured at predawn or in actual photochemical yield [(F(m)'-F(s))/F(m)'] measured at midday. Moreover, growth rates of the plants were the same, as were the leaf area ratio, plant height and leaf number. Similarly, antisense plants did not exhibit greater susceptibility to photoinhibition than controls under field conditions. In contrast, when chloroplast protein (D1) synthesis was inhibited by lincomycin, antisense plants were more vulnerable to photoinhibition than wild-type plants. These results indicate that photoprotection under field conditions is not strictly dependent on the levels of the de-epoxidized xanthophylls, antheraxanthin and zeaxanthin.

Journal Article↗
PubMed2001

Heterogeneity in nuclear transport does not affect the timing of DNA synthesis in quiescent mammalian nuclei induced to replicate in Xenopus egg extracts.

Intact G0 nuclei from quiescent mammalian cells initiate DNA synthesis asynchronously in Xenopus egg extracts, despite exposure to the same concentration of replication factors. This indicates that individual nuclei differ in their ability to respond to the inducers of DNA replication. Since the induction of DNA synthesis requires the accumulation of replication factors by active nuclear transport, any variation in the rate of transport among nuclei could contribute to the variability of DNA replication. Using the naturally fluorescent protein allophycocyanin (APC) coupled with the nuclear localization sequence (NLS) of SV40 T antigen, as a marker of nuclear uptake, we show here that individual G0 nuclei differ in their rate of transport over a range of more than 20-fold. Surprisingly, this variation has no direct influence on the timing or extent of DNA synthesis. Similar results were obtained by monitoring the uptake of nucleoplasmin, a nuclear protein present at high levels in egg extracts. These experiments show that the initiation of DNA synthesis is not driven merely by the accumulation of replication factors to some threshold concentration. Instead, some other explanation is needed to account for the timing of initiation.

Amino Acid Sequence↗
PubMed2001

Effects of osutidine (T-593) and its enantiomers on gastric mucosal hemodynamics and mucosal integrity in anesthetized rats.

T-593 (osutidine, CAS 140695-21-2) is a new anti-ulcer agent that consists of two enantiomers, (+)-(R)-T-593 and (-)-(S)-T-593. The present study was designed to investigate the effects of T-593, (+)-(R)-T-593 and (-)-(S)-T-593 on ethanol-induced gastric damage in rats. Rats were given intraperitoneal administration of vehicle, racemic T-593, (+)-(R)-T-593 or (-)-(S)-T-593. 30 min later, the rats intragastrically received a 1-ml solution of 40% ethanol, and 30 min thereafter, they were sacrificed for assessment of gastric damage. Gastric hemodynamics were assessed by reflectance spectrophotometry and laser Doppler flowmetry during the experiment. Gastric damage was significantly suppressed by racemic T-593 in a dose-dependent manner. While 60 mg/kg of (+)-(R)-T-593 and (-)-(S)-T-593 also suppressed ethanol-induced gastric injury, the same dose of racemic T-593 exerted the most potent anti-ulcerative activity. Both (+)-(R)-T-593 and racemic T-593 increased gastric mucosal blood flow and abolished gastric mucosal blood flow stasis induced by 40% ethanol. Although (-)-(S)-T-593, which antagonizes histamine H2-receptors, exerts an antiulcerative effect, (+)-(R)-T-593 also protects the gastric mucosa from ethanol-induced injury, possibly by influencing gastric mucosal hemodynamics. Thus racemic T-593 may protect the gastric mucosa by antagonizing H2-receptors and by enhancing gastric circulation in rats.

Anesthesia↗
PubMed2000

Selective instability of Orc1 protein accounts for the absence of functional origin recognition complexes during the M-G(1) transition in mammals.

To investigate the events leading to initiation of DNA replication in mammalian chromosomes, the time when hamster origin recognition complexes (ORCs) became functional was related to the time when Orc1, Orc2 and Mcm3 proteins became stably bound to hamster chromatin. Functional ORCs, defined as those able to initiate DNA replication, were absent during mitosis and early G(1) phase, and reappeared as cells progressed through G(1) phase. Immunoblotting analysis revealed that hamster Orc1 and Orc2 proteins were present in nuclei at equivalent concentrations throughout the cell cycle, but only Orc2 was stably bound to chromatin. Orc1 and Mcm3 were easily eluted from chromatin during mitosis and early G(1) phase, but became stably bound during mid-G(1) phase, concomitant with the appearance of a functional pre-replication complex at a hamster replication origin. Since hamster Orc proteins are closely related to their human and mouse homologs, the unexpected behavior of hamster Orc1 provides a novel mechanism in mammals for delaying assembly of pre-replication complexes until mitosis is complete and a nuclear structure has formed.

Amino Acid Sequence↗
PubMed2000

Induction of DNA synthesis or apoptosis in mammalian nuclei by Xenopus egg extracts that fail to support the replication of sperm chromatin.

Cell-free extracts of Xenopus eggs are widely used to study DNA replication in higher eukaryotes. However, with Xenopus sperm chromatin as template, it is a common experience that the efficiency of replication varies from extract to extract, for reasons that are unclear. Here we show that the majority of extracts unable to support sperm replication are nevertheless able to induce DNA synthesis in intact mammalian nuclei. Those that do not, induce apoptosis.

3T3 Cells↗
PubMed2000

Antisense suppression of violaxanthin de-epoxidase in tobacco does not affect plant performance in controlled growth conditions.

Violaxanthin de-epoxidase (VDE) catalyzes the de-epoxidation of violaxanthin to antheraxanthin and zeaxanthin in the xanthophyll cycle. Tobacco was transformed with an antisense VDE construct under control of the cauliflower mosaic virus 35S promoter to determine the effect of reduced levels of VDE on plant growth. Screening of 40 independent transformants revealed 18 antisense lines with reduced levels of VDE activity with two in particular (TAS32 and TAS39) having greater than 95% reduction in VDE activity. Northern analysis demonstrated that these transformants had greatly suppressed levels of VDE mRNA. De-epoxidation of violaxanthin was inhibited to such an extent that no zeaxanthin and only very low levels of antheraxanthin could be detected after exposure of leaves to high light (2000 mumol m(-2) s(-1) for 20 min) with no observable effect on levels of other carotenoids and chlorophyll. Non-photochemical quenching was greatly reduced in the antisense VDE tobacco, demonstrating that a significant level of the non-photochemical quenching in tobacco requires de-epoxidation of violaxanthin. Although the antisense plants demonstrated a greatly impaired de-epoxidation of violaxanthin, no effect on plant growth or photosynthetic rate was found when plants were grown at a photon flux density of 500 or 1000 mumol m(-2) s(-1) under controlled growth conditions as compared to wild-type tobacco.

Journal Article↗
PubMed2000

Cyclo-oxygenase-2 inhibitors suppress epithelial cell kinetics and delay gastric wound healing in rats.

BACKGROUND AND AIMS: The present study examined the effects of NS-398, a specific cyclo-oxygenase-2 inhibitor, on gastric mucosal cell kinetics and gastric wound healing following acid-induced injury. METHODS: Male Sprague-Dawley rats were fasted for 24 h and then 0.6 mol/L hydrochloric acid (HCl; 1 mL) was administered into the stomach; NS-398 or indomethacin was administered to the animals 10 min after the acid. Levels of constitutive cyclo-oxygenase (COX-1) and mitogen-inducible cyclo-oxygenase (COX-2) in the gastric mucosa were analysed using western blotting and immunohistochemical staining. The grade of the lesion was assessed using planimetry and histological examination, including immunohistochemistry for proliferating cell nuclear antigen (PCNA). RESULTS: Although there was strong expression of COX-1, there was minimal expression of COX-2 in the gastric mucosa. Expression of COX-2 was enhanced mainly in surface epithelial cells and neck cells following HCl administration. Gastric mucosal ulcers and erosions healed within 48 h, during which time the proliferative zone expanded in the control animals. Indomethacin and NS-398 suppressed the expansion of the proliferative zone and delayed the healing of the gastric injury. CONCLUSION: The present study demonstrated that cyclo-oxygenase-2 inhibitors delay gastric wound healing by suppressing expansion of the mucosal proliferative zone. These results provide evidence that cyclo-oxygenase-2 has an important role in gastric mucosal regeneration.

Animals↗
PubMed2000

Induction of cyclooxygenase-2 in rat gastric mucosa by rebamipide, a mucoprotective agent.

Recent studies indicate an expression of mitogen-inducible cyclooxygenase (COX-2) in gastric mucosa. Rebamipide, a mucoprotective agent enhances prostaglandin (PG) synthesis. The present study was designed to clarify the mechanism for rebamipide-induced mucosal protection. Male Sprague-Dawley rats were administered 5, 15, or 50 mg/kg/day rebamipide for 14 days. The expression of constitutive cyclooxygenase (COX-1) and COX-2 in gastric mucosa was determined using Western blot analysis. Another series of rats was used to examine 1) the levels of PGE(2) in stomach with and without pretreatment with a COX-2 inhibitor; 2) the protective action of rebamipide against gastric damage caused by 0.6 N HCl; and 3) the effects of a COX-2 inhibitor on rebamipide-induced gastric mucosal protection. COX-2 expression was enhanced, whereas COX-1 expression did not change significantly in the gastric mucosa of rats after treatment with rebamipide. The gastric mucosal PGE(2) was higher in the rebamipide groups than in the vehicle-treated group. Rebamipide also suppressed gastric damage induced by HCl in a dose-dependent manner. A COX-2 inhibitor blocked the rebamipide-induced increase in mucosal PGE(2), and mucosal protection induced by rebamipide. The results indicate that rebamipide induces COX-2 expression, increases PGE(2) levels, and enhances gastric mucosal defense in a COX-2-dependent manner. Thus, COX-2 has an important role in the effects of rebamipide on gastric mucosal protection.

Alanine↗
PubMed2000

[Application of autotransfusion hemodilution in laryngectomy].

OBJECTIVE: To study the application and clinical significance of autotransfusion hemodilution in laryngectomy. METHOD: Autotransfusion hemodilution was adopted in 30 patients with III or IV stage laryngeal carcinoma during operation as the experimental group, and the blood transfusion only was adopted in the patients with excessively blood loss. The other 30 patients with the same stages of disease and the same kinds of operation were performed as the control group, without autotransfusion hemodilution and the blood transfusion was adopted if necessary. RESULT: Blood transfusion was necessary to be performed only in 8 patients of the experimental group, on the contrary, it was necessary in 19 of 30 patients of the control group (P < 0.01). There were no complications during the operations, and the postoperative complications were no significance (P > 0.05) between two groups. CONCLUSION: The application of autotransfusion hemodilution may be of help to a plenty of patients with laryngeal carcinoma in advanced stage to keep off the blood transfusion during laryngectomy.

Adult↗
PubMed1998

Estrogen inhibits phorbol ester-induced I kappa B alpha transcription and protein degradation.

Estrogen (E2) is known to prevent bone loss and the mechanism is, at least in part, mediated by inhibition of expression of cytokines such as interleukin-6 (IL-6). Expression of IL-6 is tightly regulated and the transcription factor NF kappa B can upregulate IL-6 gene expression by binding to its promoter region. NF kappa B is kept in an inactive state by associating with its cytoplasmic inhibitor I kappa B alpha. Upon mitogenic stimulation, I kappa B alpha becomes phosphorylated, followed by a rapid protein degradation. As a result, NF kappa B is released and translocate to the nucleus where DNA binding occurs. It has been shown that E2 treatment downregulates mitogen-induced IL-6 expression by inhibiting NF kappa B activity. Here, we sought to determine whether E2 regulates IL-6 gene expression by modulating the levels of I kappa B alpha. Our results show that E2 treatment almost completely inhibits phorbol ester-induced I kappa B alpha protein degradation. In addition, E2 inhibits phorbol ester-stimulated I kappa B alpha gene expression. Taken together, our results suggest that E2 maintains steady state levels of I kappa B alpha upon mitogen stimulation, resulting in inhibition of NF kappa B activation and IL-6 gene expression. This may explain the protective effect of E2 on bone loss.

DNA-Binding Proteins↗
PubMed1998

Interferon-alpha resistance in a cutaneous T-cell lymphoma cell line is associated with lack of STAT1 expression.

Interferon-alpha (IFN alpha) mediates its biological effects through activation of the JAK-STAT signaling pathway and it has been shown to be one of most effective therapeutic agents for a number of hematological malignancies, including cutaneous T-cell lymphoma (CTCL). Nevertheless, its efficacy is limited by the development of clinical resistance but the reasons for resistance in CTCL are unknown. Here, we report the development of an IFN alpha-resistant CTCL cell line (HUT78R), characterized by its ability to proliferate in high concentration of recombinant IFN alpha, which can be used as a model system to study IFN resistance. The levels of IFN receptor expression and binding affinity were found to be comparable between the parental sensitive (HUT78S) and resistant (HUT78R) cells. However, IFN alpha stimulation failed to induce interferon-stimulated gene factor 3 (ISGF3) complex formation in HUT78R cells. In addition, the expression of the IFN-inducible 2-5 OAS gene was significantly reduced in HUT78R cells, suggesting the presence of a defect in the Jak-STAT signaling pathway. Our results showed that the IFN alpha-activated form of a latent transcriptional factor STAT1 was not found in HUT78R cells, whereas activated STAT2 and STAT3 were clearly detectable. By Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses, we found that HUT78R cells do not express any STAT1 protein or mRNA, suggesting the possibility of a null mutation in the STAT1 gene. Resistance to the growth inhibitory effect of IFN alpha in CTCL cells may result from lack of STAT1 expression.

Antineoplastic Agents↗
PubMed1998

Interleukin 12 administration enhances Th1 activity but delays recovery from influenza A virus infection in mice.

Interleukin 12 (IL-12) directs the differentiation of undifferentiated T helper (Th0) cells to T helper type 1 (Th1) cells and induces a cell-mediated immune response. To evaluate the effect of IL-12 on the course of influenza A virus infection, BALB/c mice were administered a daily intraperitoneal dose of 1000 ng of IL-12 or saline on days -1 to +4 for a total of six treatments. The treatment generally enhanced Th1-mediated responses. IFNgamma lung concentrations were 1193 +/- 275 pg/100 microl in controls and 3693 +/- 745 pg/100 microl in IL-12-treated mice at day 5. IFNgamma levels were undetectable at day 13 in controls and 1335 +/- 220 pg/100 microl in IL-12-treated mice. Cytokine production was also assessed at the single-cell level for mediastinal lymph nodes. IL-12 treatment increased the number of IL-2- and IFNgamma-producing cells and decreased the number of IL-4- and IL-10-producing cells. IL-12 treatment decreased the anti-influenza antibody response, especially anti-influenza IgG1 antibody resulting in an increased IgG2a/IgG1 ratio. Primary pulmonary CTL activity on day 5 was low for both groups (10% specific lysis). Secondary CTL activity at day 11 was higher for control mice than for IL-12-treated mice on day 11 (44 versus 34%), but not on day 13. Despite this overall enhancement of Th1-mediated immune functions, the IL-12 treatment increased severity of the disease. Following infection, control and IL-12-treated mice decreased their body weight to approximately 75% of their initial weight. After day 5, the control mice started to recover, while IL-12-treated mice did not begin recovering until day 9. Pulmonary viral titers were 1.6 +/- 0.3 TCID50 in controls at day 5 compared to 2.4 +/- 0.3 for IL-12-treated mice (P < 0.01). In addition, control mice had significantly less severe inflammation and damage on histologic examination. Serum TNFalpha concentrations, undetectable in control mice, were elevated by IL-12 treatment up to 80 pg/ml at day 5 and decreased to zero at day 13. It is concluded that IL-12 administration to influenza-infected mice induces a switch from a Th2- to a Th1-mediated response, but inhibits recovery probably through induction of TNFalpha.

Animals↗
PubMed1997

Helicobacter pylori and gastric carcinogenesis.

This article consists of three independent studies regarding Helicobacter pylori-related gastric carcinogenesis. Ammonia, a Helicobacter product, promoted chemically induced gastric carcinogenesis in animals. Moreover, an extract of Helicobacter stimulated inflammatory production of nitric oxide (NO), a potent mutagen that causes G:C-->A:T transition. Meta-analysis of recent studies demonstrated that G:C-->A:T transition is one of the most common mutations in the p53 tumor suppressor gene in early phases of human gastric carcinogenesis. Therefore, bacterial factors such as ammonia and host factors, including inflammatory NO production, might play important roles in H. pylori-induced gastric carcinogenesis.

Ammonia↗
PubMed1996

Gene gun-mediated skin transfection with interleukin 12 gene results in regression of established primary and metastatic murine tumors.

Particle-mediated (gene gun) in vivo delivery of the murine interleukin 12 (IL-12) gene in an expression plasmid was evaluated for antitumor activity. Transfer of IL-12 cDNA into epidermal cells overlying an implanted intradermal tumor resulted in detectable levels (266.0 +/- 27.8 pg) of the transgenic protein at the skin tissue treatment site. Despite these low levels of transgenic IL-12, complete regression of established tumors (0.4-0.8 cm in diameter) was achieved in mice bearing Renca, MethA, SA-1, or L5178Y syngeneic tumors. Only one to four treatments with IL-12 cDNA-coated particles, starting on day 7 after tumor cell implantation, were required to achieve complete tumor regression. This antitumor effect was CD8+ T cell-dependent and led to the generation of tumor-specific immunological memory. By using a metastatic P815 tumor model, we further showed that a delivery of IL-12 cDNA into the skin overlying an advanced intradermal tumor, followed by tumor excision and three additional IL-12 gene transfections, could significantly inhibit systemic metastases, resulting in extended survival of test mice. These results suggest that gene gun-mediated in vivo delivery of IL-12 cDNA should be further developed for potential clinical testing as an approach for human cancer gene therapy.

Animals↗