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Biomedical subjects

W K Ho

Publications and source records attributed to W K Ho.

At least 37 records · Page 2Linked to original sources
PubMed2001

Phosphatidylinositol 4,5-bisphosphate is acting as a signal molecule in alpha(1)-adrenergic pathway via the modulation of acetylcholine-activated K(+) channels in mouse atrial myocytes.

We have investigated the effect of alpha(1)-adrenergic agonist phenylephrine (PE) on acetylcholine-activated K(+) currents (I(KACh)). I(KACh) was recorded in mouse atrial myocytes using the patch clamp technique. I(KACh) was activated by 10 microm ACh and the current decreased by 44.27 +/- 2.38% (n = 12) during 4 min due to ACh-induced desensitization. When PE was applied with ACh, the extent of desensitization was markedly increased to 69.34 +/- 2.22% (n = 9), indicating the presence of PE-induced desensitization. I(KACh) was fully recovered from desensitization after a 6-min washout. PE-induced desensitization of I(KACh) was not affected by protein kinase C inhibitor, calphostin C, but abolished by phospholipase C (PLC) inhibitor, neomycin. When phophatidylinositol 4,5-bisphosphate (PIP(2)) replenishment was blocked by wortmannin (an inhibitor of phophatidylinositol 3-kinase and phophatidylinositol 4-kinase), desensitization of I(KACh) in the presence of PE was further increased (97.25 +/- 7.63%, n = 6). Furthermore, the recovery from PE-induced desensitization was inhibited, and the amplitude of I(KACh) at the second exposure after washout was reduced to 19.65 +/- 2.61% (n = 6) of the preceding level. These data suggest that the K(ACh) channel is modulated by PE through PLC stimulation and depletion of PIP(2).

Acetylcholine↗
PubMed2001

Management of extensive cervical nodal metastasis in nasopharyngeal carcinoma after radiotherapy: a clinicopathological study.

OBJECTIVES: To evaluate the efficacy of afterloading brachytherapy following radical neck dissection (RND) in the management of extensive cervical lymph node disease in nasopharyngeal carcinoma after radiotherapy; and to examine prospectively prognostic factors and the pathologic behavior of neck disease. PATIENTS: Twenty-seven patients with nasopharyngeal carcinoma who had extensive cervical lymph node metastasis following external radiotherapy were treated with RND. Thirteen of them also underwent afterloading brachytherapy with iridium wire (Ir 192). The RND specimens of the 27 patients were also examined with step serial whole-specimen sectioning. RESULTS: All patients survived and their wounds healed primarily. Pathologic examination revealed 183 tumor-bearing lymph nodes that contained tumors in the neck: level I, 4% (8/183); level II, 53% (96/183); level III, 34% (62/183); level IV, 5% (9/183); and level V, 4% (8/183). Extracapsular tumor extension was seen in 84% of patients. Multivariate analysis identified the number of tumor-bearing lymph nodes detected in the specimens to be the only significant factor that affected control of disease. Although the neck disease in the group of patients who had afterloading brachytherapy was more extensive, the 3-year actuarial tumor control for the groups with and without brachytherapy were 60% and 61%, respectively. CONCLUSIONS: Recurrent cervical lymph nodes after radiotherapy in nasopharyngeal carcinoma are extensive and RND is mandatory for a successful salvage. When the nodal metastasis infiltrate or adhere to surrounding tissue, afterloading brachytherapy with iridium wire can provide satisfactory local tumor control.

Adult↗
PubMed2001

Prognostic significance of serum p53 protein and p53 antibody in patients with surgical treatment for head and neck squamous cell carcinoma.

OBJECTIVES: This study aims at investigating the prognostic values of serum p53 protein and anti-p53 antibody in patients undergoing surgical treatment for head and neck squamous cell carcinoma (HNSCC). METHODS: Serum p53 protein and anti-p53 antibody concentrations were determined by an enzyme-linked immunosorbent assay (ELISA) in 75 patients with HNSCC and 28 healthy controls. In 28 patients, formalin-fixed tumor tissues were also available for immunohistochemical staining by an anti-p53 DO7 monoclonal antibody. The results were correlated with the clinicopathologic parameters. RESULTS: The mean preoperative serum concentration of p53 protein in patients with HNSCC was significantly higher than healthy controls (59.45 pg/mL vs 16.4 pg/mL, p =.007). Preoperative serum p53 antibody was present in 23 (31%) patients and was present in one healthy control. Eighteen (62%) tumor tissues showed p53 overexpression by immunohistochemistry. The presence of serum anti-p53 antibody before operation was associated with a significantly higher incidence (65%) of nodal metastasis compared with 27% nodal metastasis in patients with absence of serum anti-p53 antibody (p =.002). CONCLUSION: Preoperative serum p53 antibody was a significant prognostic factor for nodal metastasis of HNSCC.

Adult↗
PubMed2001

A comparative study of the clinicopathological significance of E-cadherin and catenins (alpha, beta, gamma) expression in the surgical management of oral tongue carcinoma.

PURPOSE: E-cadherin and catenins are important epithelial adhesion molecules in normal epithelium. Loss of E-cadherin-catenin adhesion is an important step in the progression of many epithelial cancers. E-cadherin and catenins expression in carcinoma of the tongue were evaluated in relation to their clinicopathological features and prognostic values. METHOD: Immunohistochemical staining was carried out with E-cadherin and (alpha, beta, gamma)-catenin monoclonal antibodies for 85 surgical specimens of oral tongue carcinoma, nine matched metastatic lymph nodes, and seven locally recurrent tumours. RESULTS: There was under-expression in 85% of E-cadherin, 94% of alpha-catenin, 89% of beta-catenin, and 83% of gamma-catenin in the primary tumours. There was no correlation of E-cadherin/catenin expression with sex, age, cancer stage, and differentiation. Nodal metastasis was found in 68% of patients with weak expression of gamma-catenin compared with 9% with strong expression in primary tumours (chi-square, P = 0.02). E-cadherin was a significant prognostic factor for survival and recurrence; patients with weak E-cadherin expression had 53% 5-year survival compared with 85% with strong expression (Wilcoxon, P = 0.0159). CONCLUSIONS: Both E-cadherin and catenins were highly under-expressed in oral tongue carcinoma, metastatic lymph node, and recurrent tumour. gamma-catenin had predictive value for nodal metastasis. E-cadherin was, however, a more important prognostic factor for recurrence and survival.

Adolescent↗
PubMed2001

Inhibition of acetylcholine-activated K(+) currents by U73122 is mediated by the inhibition of PIP(2)-channel interaction.

1. We have investigated the effect of U73122, a specific inhibitor of phospholipase C (PLC), on acetylcholine-activated K(+) currents (I(KACh)) in mouse atrial myocytes. 2. In perforated patch clamp mode, I(KACh) was activated by 10 microM acetylcholine. When atrial myocytes were pretreated with U73122 or U73343, I(KACh) was inhibited dose-dependently (half-maximal inhibition at 0.12+/-0.0085 and 0.16+/-0.0176 microM, respectively). The current-voltage relationships for I(KACh) in the absence and in the presence of U73122 showed that the inhibition occurred uniformly from -120 to +40 mV, indicating a voltage-independent inhibition. 3. When U73122 was applied after I(KACh) reached steady-state, a gradual decrease in I(KACh) was observed. The time course of the current decrease was well fitted to a single exponential, and the rate constant was proportional to the concentration of U73122. 4. When K(ACh) channels were directly activated by adding 1 mM GTP gamma S to the bath solution in inside-out patches, U73122 (1 microM) decreased the open probability significantly without change in mean open time. When K(ACh) channels were activated independently of G-protein activation by 20 mM Na(+), open probability was also inhibited by U73122. 5. Voltage-activated K(+) currents and inward rectifying K(+) currents were not affected by U73122. 6. These findings show that inhibition by U73122 and U73343 of K(ACh) channels occurs at a level downstream of the action of G beta gamma or Na(+) on channel activation. The interference with phosphatidylinositol 4,5-bisphosphate (PIP(2))-channel interaction can be suggested as a most plausible mechanism.

Acetylcholine↗
PubMed2001

The clinicopathological significance of bcl-2 expression in the surgical treatment of laryngeal carcinoma.

Bcl-2 expression was studied by immunohistochemistry on laryngectomy specimens from 176 patients. Of the 176 tumours, 11% had positive bcl-2 staining. Bcl-2 expression was significantly correlated with tumour grade: 5% of well-differentiated tumours, 12% of moderately-differentiated tumours and 23% of poorly-differentiated tumours had positive expression of bcl-2. Nodal metastases were also found to be significantly related to bcl-2 expression: 36% of nodal metastases for negative bcl-2 expression compared with 70% for positive expression. The risk of nodal metastases increased significantly with the presence of bcl-2 expression, moderate or poor differentiation and supraglottic involvement. The risk of nodal metastases increased significantly with the presence of increasing numbers of risk factors: 11% without risk factor, 21% with one risk factor, 49% with two risk factors and 77% with three risk factors. Bcl-2 expression in laryngeal carcinoma is significantly correlated with tumour grade and nodal metastases. It has added prognostic value for nodal metastases together with tumour grade and site of tumour involvement.

Carcinoma, Squamous Cell↗
PubMed2001

Development of follicular dendritic cell sarcoma in hyaline-vascular Castleman's disease of the nasopharynx: tracing its evolution by sequential biopsies.

AIMS: Hyaline-vascular Castleman's disease (HVCD) and follicular dendritic cell (FDC) sarcoma occurring in the nasopharynx are both extremely rare. We report the first case of transformation of the former into the latter as documented by sequential biopsies. The steps involved in the transformation were described in detail and the possible role of p53 studied. METHODS AND RESULTS: The patient presented at the age of 23 years with nasopharyngeal HVCD. Hyaline- vascular Castleman's disease with FDC overgrowth was diagnosed in a recurrence 8 years later, and a frank FDC sarcoma developed at the same site 11 years after initial presentation. The patient remained disease-free 3 years after excision and adjuvant chemotherapy. The FDC sarcoma comprised swirling fascicles of spindly cells with indistinct cell borders. The tumour cells expressed the FDC markers CD21, CD35 and CNA.42 and in-situ hybridization for Epstein-Barr virus-encoded RNAs was negative. Over-expression of p53 protein was observed in the FDC sarcoma and an increased number of weakly p53-positive spindly cells could also be demonstrated in the HVCD specimen. This finding suggested a possible role of p53 in the evolution from HVCD to FDC sarcoma. Critical analysis of the literature shows that, among the 13 reported cases of FDC sarcoma associated with Castleman's disease, possible progression from the latter to the former is documented in only two cases. CONCLUSIONS: The sequential changes observed in the current case provide further evidence to strengthen the role of HVCD as a possible precursor of FDC sarcoma. There is a possible role of p53 in the transformation process but confirmation by future studies is needed.

Adult↗
PubMed2001

Prospective randomized study of post-operative chemotherapy with levamisole and UFT for head and neck carcinoma.

AIMS: A prospective randomized study was conducted to evaluate the benefit of adjuvant levamisole/UFT (futraful and uracil) chemotherapy in head and neck squamous cell carcinoma. METHODS: Sixty-five patients with stage III and IV squamous cell carcinomas of oral cavity, oropharynx, hypopharynx and larynx with no distant metastasis were randomized for the chemotherapy study. Thirty-one patients were randomized for chemotherapy and two of them were subsequently excluded. In this study, a total of 29 patients on levamisole/UFT therapy and 34 patients on the control group were analysed. The main outcome was measured by the 5-year disease-free actuarial survival rate. RESULTS: The rates of distant metastasis were 10% for chemotherapy group and 32% for control group (P=0.06). The 5-year disease-free actuarial survival rates for patients with and without adjuvant chemotherapy were 57% and 39% respectively (P=0.207). CONCLUSIONS: A trend of better distant control in head and neck cancer patients with post-operative adjuvant oral chemotherapy was observed. The side effects were minimal. However, there was no statistically significant improvement in the overall long-term survival. It may be of value to conduct a large-scale multi-centre prospective randomized study to verify the efficacy of levamisole and UFT as post-operative adjuvant chemotherapy for the control of distant metastasis in high-risk population.

Adjuvants, Immunologic↗
PubMed2001

Relationship between the size of neopharynx after laryngectomy and long-term swallowing function: an assessment by scintigraphy.

OBJECTIVES: To study the relationship between the size of neopharynx after total laryngectomy and long-term swallowing function by means of scintigraphy. STUDY DESIGN: The width of pharyngeal remnant was measured during surgery in 11 patients. Their swallowing function was assessed by scintigraphy 8 to 10 years after surgery. METHODS: The width of pharyngeal remnant at its narrowest point in both relaxed and stretched state was measured during surgery. Postoperative scintigraphy data on swallowing were obtained and computed along 3 lines, (1) transit time through neopharynx, (2) percentage of bolus transferred, and (3) swallowing efficiency. The relationship between the 2 sets of data was analyzed by linear regression analysis. RESULTS: (1) No statistically significant relationship was found between the size of neopharynx and swallowing function. (2) All patients are clinically asymptomatic. CONCLUSIONS: The swallowing function is not affected by the size of the neopharynx in 11 patients with pharyngeal remnant width ranging from 3 to 8 cm (stretched).

Aged↗
PubMed2001

The clinicopathologic significance of p53 and p21 expression in the surgical management of lingual squamous cell carcinoma.

The aim of the present study was to evaluate the clinicopathologic significance of p53 and p21 expression in lingual squamous cell carcinomas. Immunohistochemical staining was performed with p53 and p21 monoclonal antibodies on surgical specimens from 87 patients who underwent primary surgical treatment for lingual carcinoma between 1976 and 1996. We found positive expression of p53 in 45 (52%) of 87 cases and of p21 in 49 (56%) of 87 cases. There was no correlation of p53 and p21 expression with cancer stage, T stage, nodal metastasis, and tumor grade. Univariate analysis revealed that p21 expression, tumor stage, T stage, and nodal stage were significant prognostic factors for survival. However, only p21 expression and tumor stage were significant independent prognostic factors for survival in a multivariate Cox regression analysis. Overexpression of p21 but not p53 has prognostic value for survival in the surgical treatment of lingual carcinomas. The combination of stage with p21 expression is recommended for evaluation of prognosis and for management planning.

Adult↗
PubMed2000

Stretch-activated and background non-selective cation channels in rat atrial myocytes.

1. Stretch-activated channels (SACs) were studied in isolated rat atrial myocytes using the whole-cell and single-channel patch clamp techniques. Longitudinal stretch was applied by using two patch electrodes. 2. In current clamp configuration, mechanical stretch of 20 % of resting cell length depolarised the resting membrane potential (RMP) from -63.6 +/- 0.58 mV (n = 19) to -54.6 +/- 2.4 mV (n = 13) and prolonged the action potential duration (APD) by 32.2 +/- 8.8 ms (n = 7). Depolarisation, if strong enough, triggered spontaneous APs. In the voltage clamp configuration, stretch increased membrane conductance in a progressive manner. The current-voltage (I-V ) relationship of the stretch-activated current (ISAC) was linear and reversed at -6.1 +/- 3.7 mV (n = 7). 3. The inward component of ISAC was abolished by the replacement of Na+ with NMDG+, but ISAC was hardly altered by the Cl- channel blocker DIDS or removal of external Cl-. The permeability ratio for various cations (PCs:PNa:PLi = 1.05:1:0.98) indicated that the SAC current was a non-selective cation current (ISAC,NC). The background current was also found to be non-selective to cations (INSC,b); the permeability ratio (PCs:PNa:PLi = 1.49:1:0.70) was different from that of ISAC,NC. 4. Gadolinium (Gd3+) acted on INSC,b and ISAC,NC differently. Gd3+ inhibited INSC,b in a concentration-dependent manner with an IC50 value of 46.2 +/- 0.8 microM (n = 5). Consistent with this effect, Gd3+ hyperpolarised the resting membrane potential (-71.1 +/- 0.26 mV, n = 9). In the presence of Gd3+ (0.1 mM), stretch still induced ISAC,NC and diastolic depolarisation. 5. Single-channel activities were recorded in isotonic Na+ and Cs+ solutions using the inside-out configuration. In NMDG+ solution, outward currents were abolished. Gd3+ (100 microM) strongly inhibited channel opening both from the inside and outside. In the presence of Gd3+ (100 microM) in the pipette solution, an increase in pipette pressure induced an increase in channel opening (21.27 +/- 0.24 pS; n = 7), which was distinct from background activity. 6. We concluded from the above results that longitudinal stret in rat atrial myocytes induces the activation of non-selective cation channels that can be distinguished from background channels by their different electrophysiology and pharmacology.

Action Potentials↗
PubMed2000

Preliminary study of in vivo autofluorescence of nasopharyngeal carcinoma and normal tissue.

BACKGROUND AND OBJECTIVE: In nasopharyngeal cancer, conventional white light endoscopy does not provide adequate information to detect the flat/small lesion and identify the margin of observable tumor. In the present study, we evaluate the potential of light-induced fluorescence spectroscopic imaging for the localization of cancerous nasopharyngeal tissue. STUDY DESIGN/MATERIALS AND METHODS: We built a multiple channel spectrometer specifically for the investigation of fluorescence collected by a conventional endoscopic system. Nasopharyngeal fluorescence were measured in vivo from 27 subjects during the routine endoscopy. The biopsy specimens for histologic analysis were taken from the tissue sites where the fluorescence were measured. RESULTS: Two algorithms to discriminate the nasopharyngeal carcinoma from normal tissue were created based on the good correlation between the tissue autofluorescence and histologic diagnosis. For the two-wavelength algorithm, carcinoma can be differentiated from normal tissue with a sensitivity and specificity of 93% and 92%, respectively. For the three-wavelength algorithm with compensation of variation of blood content in tissue, a sensitivity of 98% and specificity of 95% were achieved. CONCLUSION: Fluorescence endoscopic imaging used with the algorithms developed in this report is an efficient method for detecting the nasopharyngeal carcinoma.

Algorithms↗
PubMed2000

Evidence of enhancement of malate-aspartate shuttle activity in beta cells of streptozotocin-induced non-insulin-dependent diabetic rats.

Glucose-induced insulin secretion is selectively impaired in beta cells from animals with non-insulin-dependent diabetes mellitus (NIDDM). This study was performed to clarify whether the malate-aspartate shuttle among the glucose metabolic pathways is intact in beta cells of NIDDM rats. The insulin secretory capacity of the islets and the K(ATP) channel activity in single beta cells were measured in control and NIDDM rats injected with streptozotocin (STZ) during the neonatal period, using a radioimmunoassay and patch-clamp technique. The increase of insulin secretion induced by 11.1 mmol/L glucose or 10 mmol/L dihydroxyacetone (DHA) was significantly reduced in NIDDM islets, suggesting an impaired glycerol-phosphate shuttle. The application of glyceraldehyde (10 mmol/L) in NIDDM or control islets elicited an increase in insulin secretion, but the difference between the 2 groups was indistinguishable. On the contrary, the increase of insulin secretion and the inhibition of K(ATP) channel activity induced by aspartate, which preferentially participates in the malate-aspartate shuttle, were significantly greater in NIDDM versus the control. However, intracellularly applied aspartate in the inside-out mode did not inhibit K(ATP) channel activity. These findings show that malate-aspartate shuttle activity is potentiated in pancreatic beta cells of NIDDM rats, suggesting the development of a compensatory mechanism for the reduced activity of the glycerol-phosphate shuttle in NIDDM.

Adenosine Triphosphate↗
PubMed2000

Blockade of the HERG human cardiac K(+) channel by the antidepressant drug amitriptyline.

1. Amitriptyline has been known to induce QT prolongation and torsades de pointes which causes sudden death. We studied the effects of amitriptyline on the human ether-a-go-go-related gene (HERG) channel expressed in Xenopus oocytes and on the rapidly activating delayed rectifier K(+) current (I(Kr)) in rat atrial myocytes. 2. The amplitudes of steady-state currents and tail currents of HERG were decreased by amitriptyline dose-dependently. The decrease became more pronounced at more positive potential, suggesting that the block of HERG by amitriptyline is voltage dependent. IC(50) for amitriptyline block of HERG current was progressively decreased according to depolarization: IC(50) values at -30, -10, +10 and +30 mV were 23.0, 8.71, 5.96 and 4.66 microM, respectively. 3. Block of HERG by amitriptyline was use dependent: exhibiting a much faster block at higher activation frequency. Subsequent decrease in frequency after high activation frequency resulted in a partial relief of HERG blockade. 4. Steady-state block by amitriptyline was obtained while depolarization to +20 mV for 0.5 s was applied at 0.5 Hz: IC(50) was 3.26 microM in 2 mM [K(+)](o). It was increased to 4. 78 microM in 4 mM [K(+)](o), suggesting that the affinity of amitriptyline on HERG was decreased by external K(+). 5. In rat atrial myocytes bathed in 35 degrees C, 5 microM amitriptyline blocked I(Kr) by 55%. However, transient outward K(+) current (I(to)) was not significantly affected. 6. In summary, the data suggest that the block of HERG currents may contribute to arrhythmogenic side effects of amitriptyline.

Amitriptyline↗
PubMed2000

Chinese tonal language rehabilitation following cochlear implantation in children.

Cantonese language rehabilitation in 28 prelingually deaf children who underwent cochlear implantation was evaluated. All patients were implanted with multichannel devices and the operations went smoothly. They all had improved scores on audiological assessments and speech perception tests. The speech evaluation tests included the recognition of sounds, vowels, consonants and tone. Sentence recognition and story comprehension were both improved after training for 2 years. Cochlear implantation is a useful measure for the speech rehabilitation of prelingually profound deaf children when hearing aids are of no benefit. The multichannel implant device is of clinical significance in the rehabilitation of those patients using tonal language.

Child↗
PubMed2000

Correlation of pure tone audiogram results and hearing benefit of tympanoplasty for chronic suppurative otitis media.

The aim of this study was to evaluate the correlation between pure tone audiogram results and the subjective sensation of hearing benefit of patients who had tympanoplasty for chronic suppurative otitis media. This is a prospective study of 115 patients who had tympanoplasty between 1992 and 1994. The outcome, including a pure tone audiogram and the subjective sensation of hearing benefit, was evaluated at 1 year after operation. There were 63 (55%) patients with subjective hearing benefit after the tympanoplasty. The subjective sensation of hearing benefit correlated with the magnitude of the air conduction (AC) threshold reduction, and increased from 39% for an AC reduction of less than or equal to 10 dB to 100% for an AC reduction of more than 30 dB. The effect of the interaural AC threshold difference on the subjective sensation of hearing was not significant; improvement was felt by 92% of patients when the operated ear became the better hearing ear, and by 73% of patients when the operated ear remained the worse hearing ear. There was considerable discrepancy between the subjective hearing benefit and the pure tone audiogram results. A combination of parameters, including the air-bone gap, the AC threshold, and the subjective hearing change, is recommended in reporting the results of tympanoplasty.

Audiometry, Pure-Tone↗
PubMed2000

The training of otorhinolaryngologists in Asia.

Asian nations differ from one another in population, cultural background, ethnic tradition and economic situation. The training of otorhinolaryngologists in Asia is not in any way uniform. A questionnaire survey of 26 leading institutions in 12 countries/regions was carried out. The emphasis of investigation is towards the training programme for specialists in Otorhinolaryngology and continuous medical education (CME). The response rate of the survey was 100 per cent. The duration of training for otorhinolaryngologists ranges from three to seven years and an exit assessment is held in seven countries/regions. The training programmes are modifications of either the British or the American pattern depending on tradition. Documentation of CME is available in eight countries/regions while a defined cycle has been established in only three. Medical/health authorities or professional societies in each country contribute towards its monitoring. Better communication and sharing of experience will improve the training of otorhinolaryngologists in Asia.

Asia↗