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Biomedical subjects

W K Ho

Publications and source records attributed to W K Ho.

At least 73 records · Page 4Linked to original sources
PubMed1998

Dual effect of nitric oxide on the hyperpolarization-activated inward current (I(f)) in sino-atrial node cells of the rabbit.

Using the whole-cell voltage-clamp technique, we have investigated the effect of nitric oxide (NO) donor (sodium nitroprusside, SNP) on hyperpolarization-activated inward current, I(f), in isolated rabbit sinoatrial node (SAN) cells. I(f) in the basal state increased when NO was applied but decreased when I(f) was pre-stimulated by isoproterenol (ISO) or by adding cAMP to the pipette solution. Both the stimulatory and the inhibitory effects of NO were abolished by guanylyl cyclase inhibitor, methylene blue (MB), suggesting that the effect of NO is mediated by cGMP. The inhibitory effect of NO was abolished when I(f) was pre-stimulated by 3-isobutyl-1-methylxanthine (IBMX), which is a phosphodiesterase (PDE) inhibitor, or by adding 8Br-cAMP (which is resistant to PDE) to the pipette solution. An analogue of cGMP, 8Br-cGMP, which is a potent stimulator of cGMP-dependent protein kinase (PKG) but has little effect on PDE, did not inhibit I(f) when I(f) was pre-stimulated by ISO. In its basal state, I(f) was still increased by 8Br-cGMP, and this effect was not prevented by the pretreatment with H-7, PKG inhibitor. The effect of acetylcholine (ACh) was not identical to that of NO: I(f) decreased when pre-stimulated not only by ISO, but also by IBMX. The above results suggest that via cGMP, NO exerts a dual effect on I(f): the inhibitory effect is mediated by cGMP-stimulated PDE, and the stimulatory effect may be attributable to direct binding of cGMP to I(f) channels.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

cGMP facilitates calcium current via cGMP-dependent protein kinase in isolated rabbit ventricular myocytes.

The effect of guanosine 3',5'-cyclic monophosphate (cGMP) on L-type Ca current (ICa) was investigated in a study of rabbit ventricular myocytes using the whole-cell patch-clamp technique. Intracellular application of cGMP (100 MUm) increased ICa in the absence of isoprenaline or forskolin. 8-Bromo-cGMP (100 muM) and 8-(4-chlorophenylthio)-cGMP (8-pCPT-cGMP, 400 muM), relatively specific stimulators of cGMP-dependent protein kinase (cGMP-PK), also increased ICa. The stimulatory effect of 8-pCPT-cGMP was suppressed by Rp-8-chlorophenylthio-cGMP (400 muM), a phosphodiesterase-resistant cGMP-PK inhibitor. When ICa was increased by bath application of the non-specific phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX, 100 muM), 8-pCPT-cGMP (400 muM) resulted in additional stimulation of ICa. In the presence of 8-pCPT-cGMP, additional applications of isoprenaline (1 muM) or forskolin (1 muM) induced a further increase in ICa. From these results, it could be concluded that the activation of cGMP-dependent protein kinase is involved in the facilitation of ICa by cGMP in rabbit ventricular myocytes.

1-Methyl-3-isobutylxanthine↗
PubMed1998

Endothelium-dependent relaxation induced by hawthorn extract in rat mesenteric artery.

The extract prepared from hawthorn (Crataegus fruit) was examined for its relaxant effect in rat isolated mesenteric arteries. Hawthorn extract induced concentration-dependent relaxation of the U46619-precontracted artery with an IC50 of 0.22 +/- 0.02 mg/ml. Removal of the functional endothelium reduced by approximately 85% the maximum relaxant response to hawthorn extract. Pretreatment of the arterial tissues with N(G)-nitro-L-arginine methyl ester (3-10 microM) or methylene blue (3-10 microM) inhibited the relaxation induced by hawthorn extract, while indomethacin (10 microM) had no effect. L-arginine (3 mM) did not affect the relaxation induced by hawthorn extract but partially reversed the effect of 10 microM N(G)-nitro-L-arginine methyl ester. Iberiotoxin (100 nM) slightly but significantly inhibited the relaxant effect of hawthorn extract whilst glibenclamide (3 microM) was ineffective. Glibenclamide at 3 microM reversed the relaxation induced by pinacidil. N(G)-nitro-L-arginine methyl ester and methylene blue markedly inhibited acetylcholine-induced relaxation in endothelium-intact arteries. Hawthorn extract also reduced the contraction induced by phenylephrine (1 microM) or high Ki (60 mM) with respective IC50 values of 0.13 +/- 0.01 mg/ml and 0.11 +/- 0.01 mg/ml. In high K+-contracted arteries, hawthorn extract induced only 55% of relaxation while it caused a complete inhibition of the U46619- or phenylephrine-induced contraction. These results suggest that hawthorn contains active components which cause vasorelaxation in rat isolated mesenteric arteries. Nitric oxide but not other endothelium-derived vasoactive factors was probably involved in the relaxation induced by hawthorn extract.

Animals↗
PubMed1998

Effects of intracellular N+, M2+ and metabolites on C2+-activated K+ channels in pulmonary and ear arterial smooth muscle cells of the rabbit.

Hypoxic pulmonary vasoconstriction (HPV) is an important mechanism for matching the ventilation/perfusion ratio in the lung, but the signal transduction pathway through which hypoxia induces vasoconstriction remains unclear. We hypothesized that the decrease in K+ current induced by hypoxia is a key mechanism for HPV, and examined the effects of the substances which are expected to accumulate during hypoxia on the activity of large conductance Ca2+-activated K+ (BKCa) channels. Pulmonary and ear arterial smooth muscle cells were isolated from the rabbit using enzymatic digestion, and large conductance Ca2+-activated K+ current (IBK,Ca) was recorded in symmetrical K+ concentrations using the inside-out mode of the patch-clamp technique. Increasing the Na+ concentration on the intracellular side suppressed IBK,Ca dose dependently: 4.6, 20.9, 35.5 and 44.6 % reduction with 4, 8, 12 and 16 mM Na+, respectively. Mg2+ also reduced IBK,Ca, and the maximum reduction was obtained at 0.5 mM. Lactate, adenosine, ADP and ATP did not significantly affect IBK,Ca. There was no difference between pulmonary and ear arterial smooth muscle cells in their response to the above substances; this finding rules out modulation of BKCa channels by the various factors thought to accumulate during hypoxia as a major mechanism involved in the decrease in the K+ conductance of pulmonary arteries in hypoxia.

Adenosine↗
PubMed1997

Antigenic determination fragments of alpha-momorcharin.

Alpha momorcharin is a protein isolated from the bitter gourd. It has a number of biological activities including induction of abortion, inhibition of tumor growth and anti-HIV. All these activities may be related to the ribosome-inhibiting activity of the protein. Repeated use of alphaMMC can elicit an antigenic response which may neutralize its biological activity. To overcome this problem, we need to know which part of the molecule is the antigenic determinant. In this study, we constructed a random fragment expression library from the alphaMMC cDNA and screened it with three anti-alphaMMC sera. A total of 9 positive clones were picked and sequenced. Based on the sequence information obtained, we were able to deduce three regions at which antibodies raised against native alphaMMC seem to interact. These regions are residues 1-14, residues 71-136 and residues 195-222. Mapping of these regions against a 3D model of alphaMMC indicates that they all are located on the surface of the molecule. As residues 71-136 are found to be in close proximity to the active site involved in ribosome inactivation, treatment with a monoclonal antibody directed to this area was shown to be effective in inactivating the inhibitory effect of alphaMMC on in vitro protein synthesis.

Abortifacient Agents, Nonsteroidal↗
PubMed1997

Assessment of tracheoesophageal speech in a tonal language. A prospective study.

BACKGROUND: Tracheoesophageal puncture followed by insertion of a voice prosthesis is an increasingly popular method for voice rehabilitation after total laryngectomy. OBJECTIVE: To perform a functional assessment of voice produced by means of the Blom-Singer valve in a tonal language (Cantonese). DESIGN: Prospective study. SETTING: Hospital referral center. MAIN OUTCOME MEASURE: A 5-point scoring scale was adopted for 15 test items of speech assessment grouped into 4 categories: phonatory skills, articulation, additional factors, and general judgment. The sum of the scores for the 15 items was the final speech score. The final speech score was rated as poor, satisfactory, or excellent if it was in the range of less than 30, 31 to 45, or 46 to 75, respectively. RESULTS: Forty-four users of the Blom-Singer valve who had undergone total laryngectomy and primary tracheoesophageal puncture were available for functional assessment. The final speech score was poor in 2 patients (5%), satisfactory in 4 (9%), and excellent in 38 (86%). CONCLUSION: Chinese patients can speak satisfactory tonal language with the Blom-Singer voice prosthesis.

Adult↗
PubMed1997

Modulation of voltage-dependent K+ channel by redox potential in pulmonary and ear arterial smooth muscle cells of the rabbit.

It has been suggested that hypoxic pulmonary vasoconstriction (HPV) results from the depolarization that is induced by the suppression of K+ current in pulmonary arterial smooth muscle cells (PASMC). We tested the hypothesis that the effect of the cellular redox potential on voltage-sensitive K+ (Kv) current is involved in HPV as a primary sensing mechanism. Kv current in PASMC and ear arterial smooth muscle cells (EASMC) of the rabbit was recorded using the whole-cell patch-clamp technique, and the effect of redox agents [dithiothreitol, DTT and 2,2'-dithio-bis(5-nitropyridine), DTBNP] was tested. Kv current was decreased by DTT, but increased by DTBNP. DTT accelerated the inactivation kinetics, but did not affect steady-state activation and inactivation, whereas DTBNP accelerated activation kinetics. Kv current has a non-inactivating window in the range of from -40 mV to +10 mV. The resting membrane potential measured using the nystatin-perforated-patch method, however, lay between -50 mV and -30 mV and was not depolarized by 5 mM 4-aminopyridine. The membrane-impermeable oxidizing agent DTNB has no effect on Kv current, suggesting that redox modulation sites are intracellular sulphydryl groups. In EASMC, Kv current was decreased by DTT, but increased by DTBNP, indicating that the redox-potential-induced modulation of Kv current in EASMC and in PASMC is the same. It is therefore concluded that Kv current is modulated by the cellular redox potential, but that this modulation is not involved in HPV as a primary sensing mechanism.

Animals↗
PubMed1997

Myelin basic protein is a zinc-binding protein in brain: possible role in myelin compaction.

The zinc-binding proteins (ZnBPs) in porcine brain were characterized by the radioactive zinc-blot technique. Three ZnBPs of molecular weights about 53 kDa, 42 kDa, and 21 kDa were identified. The 53 kDa and 42 kDa ZnBPs were found in all subcellular fractions while the 21 kDa ZnBP was mainly associated with particulate fractions. This 21 kDa ZnBP was identified by internal protein sequence data as the myelin basic protein. Further characterization of its electrophoretic properties and cyanogen bromide cleavage pattern with the authentic protein confirmed its identity. The zinc binding properties of myelin basic protein are metal specific, concentration dependent and pH dependent. The zinc binding property is conferred by the histidine residues since modification of these residues by diethyl-pyrocarbonate would abolish this activity. Furthermore, zinc ion was found to potentiate myelin basic protein-induced phospholipid vesicle aggregation. It is likely that zinc plays an important role in myelin compaction by interacting with myelin basic protein.

Animals↗
PubMed1997

Results of surgical salvage of locoregional recurrence of carcinoma of the tongue after radiotherapy failure.

The aim of this study was to evaluate the efficacy of surgical salvage of local and nodal recurrence of carcinoma of the oral tongue after radiotherapy failure. Of the 47 patients in this retrospective review (between 1980 and 1992), there were 25 with local recurrence alone, 11 with locoregional recurrence, and 11 with nodal recurrence alone. There was no operative mortality, and 17% of patients had one or more surgical complications, including wound infection, flap necrosis, anastomotic leakage, and chest infection. Twenty-nine (62%) patients developed recurrences in the head and neck region after the salvage operation, and 9 of them had second surgical salvage operations. At the last follow-up, 53% of patients had died of carcinoma of the tongue and the overall 5-year actuarial survival rate was 43%. The 5-year actuarial survival rates were 39% for local recurrence alone, 27% for locoregional recurrence, and 68% for nodal recurrence alone. Surgical salvage had satisfactory results for patients with oral tongue carcinoma after radiotherapy failure. Close follow-up and early surgical intervention are essential for patients primarily treated with radiotherapy.

Adult↗
PubMed1997

Variation of the CGG repeat in FMR-1 gene in normal and fragile X Chinese subjects.

The fragile X syndrome is believed to be caused by an expansion of a CGG trinucleotide repeat segment in the FMR-1 gene on the fragile X site of the long arm of the X-chromosome. To understand the variation of the CGG repeat in the FMR-1 gene in southern Chinese from the Hong Kong and Guangzhou area, we undertook the present study. A total of 83 normal and three fragile X subjects were examined. In the normal group, 16 distinct alleles, ranging in size from 272 bp to 332 bp with 17 to 37 CGG repeats were detected. A repeat size of 29 was the most frequent. Compared with data collected in the USA, the repeat size observed in this population was somewhat smaller. Whether this discrepancy is due to ethnic difference remains to be determined. The three fragile X patients examined in this study did not have a greatly expanded CGG segment. One of them may be a mosaic with one full and one premutation allele. The other two patients, although having clinical and cytological features of fragile X syndrome, had a CGG repeat size within normal range. To explain this, we infer that the mutation in these patients may be caused by other mechanisms, such as other types of FMR-1 mutation or mutation in another site. It is possible that the expansion of the CGG repeats may not be as frequent a cause of fragile X syndrome in southern Chinese as in other ethnic groups.

Child↗
PubMed1997

Reduced dihydroxyacetone sensitivity and normal sensitivity to glyceraldehyde and oxidizing agent of ATP-sensitive K+ channels of pancreatic beta cells in NIDDM rats.

The inhibition of ATP-sensitive K+(KATP) channels in pancreatic beta cells is a key step of insulin secretion induced by glucose. Glucose-induced insulin secretion from the beta cells is selectively impaired in patients with noninsulin-dependent diabetes mellitus (NIDDM) and in animal models of it. In order to clarify the site of this abnormal glucose response, we studied the effects of insulin secretagogues and sulfhydryl oxidizing agent, 2,2'-dithio-bis (5-nitropyridine) (DTBNP), on KATP channels in single beta cells of neonatally streptozotocin-induced NIDDM rats. We used the patch-clamp technique in cell-attached mode (Vpipette = 0 mV). The inhibitory response to glucose of KATP channels was lacking in NIDDM rats, indicating reduced sensitivity to glucose of the channels. Glyceraldehyde (2-5 mM) in the diabetic beta cells elicited the same KATP channel inhibition as that obtained in controls. In contrast, dihydroxyacetone (DHA, 2-10 mM) sensitivity of KATP channels was significantly reduced in the beta cells of NIDDM rats. KATP channels in the diabetic beta cells were rapidly inhibited by 50 microM DTBNP, just as in the normal beta cells, suggesting that KATP channel function was normal. This indicates that one of the sites responsible for impaired glucose-induced insulin secretion in the pancreatic beta cells of NIDDM rats is located in the glycerol phosphate shuttle.

Adenosine Triphosphate↗
PubMed1996

Effects of volatile anesthetic isoflurane on ATP-sensitive K+ channels in rabbit ventricular myocytes.

It has been suggested that volatile anesthetic, isoflurane mediates cardioprotective effects via activation of the ATP-sensitive K+ (KATP) channels. However, no direct evidence has been provided to define whether isoflurane activates cardiac KATP channels using patch-clamp technique. We examined the effects of isoflurane on the KATP channels in rabbit ventricular myocytes by use of patch-clamp technique. Contrary to the results of the in vivo experiments, isoflurane inhibited the channel activity without a change in the single-channel conductance. Isoflurane decreased the channel activity by a decrease in burst duration and an increase in the inter-burst duration. On the other hand, isoflurane diminished the ATP sensitivity of KATP channels, indicating an increased probability of KATP channel opening for a given concentration of ATP after isoflurane anesthesia. The result supports, at least in part, the hypothesis that isoflurane mediates cardioprotective effects via KATP channel activation.

Anesthetics, Inhalation↗
PubMed1996

Sensorineural hearing loss in patients treated for nasopharyngeal carcinoma: a prospective study of the effect of radiation and cisplatin treatment.

PURPOSE: The pattern of sensorineural hearing loss (SNHL) after primary treatment for nasopharyngeal carcinoma (NPC) was studied, and the effect of cisplatin, radiotherapy does, and fractionation were evaluated. METHODS AND MATERIALS: One hundred thirty-two patients, 227 ears, and 1100 audiogram reports were analyzed. Radiotherapy dose ranged from 59.5 to 76.5 Gy. Fifty-two patients received preirradiation cisplatin, total dose 100-185 mg/m(2). Serial postirradiation bone conduction thresholds at 0.5 kHz, 1 kHz, 2 kHz, and 4 kHz were compared with pretreatment thresholds at respective frequencies. Increase of at least 15 dB was considered as significant and was further grouped as transient or persistent SNHL. Univariate and multivariate analyses were performed to identify predicting factors for persistent SNHL. RESULTS: At median follow-up of 30 months, 24.2% of ears developed persistent SNHL. High frequency was more affected than low frequencies, 22 vs. 5.3%. Males were more affected than females, 29.4 vs. 15.5%, p = 0.0132. Incidence of persistent SNHL increased with age, with 0, 17.2, and 37.4% of patients aged under 30, between 30-50 and over 50 affected, respectively, p = 0.0001. High incidence was found in patient with postirradiation serous otitis media (SOM), 46.9%. Chemotherapy with cisplatin and radiation dose or fractionation had no significant effect. Multivariate analysis confirmed age, sex, and postirradiation SOM as significant prognostic factors for persistent SNHL. CONCLUSIONS: Transient and persistent SNHL occurred after radiotherapy, more commonly affecting high frequency. A low dose of preirradiation cisplatin did not increase the risk. A dose fractionation effect of radiotherapy was not confirmed in this study.

Adolescent↗
PubMed1996

Voltage- and time-dependent block of delayed rectifier K+ current in rabbit sino-atrial node cells by external Ca2+ and Mg2+.

1. The properties of the delayed rectifier K+ current (IK) of rabbit isolated sino-atrial node cells were investigated in high (140 mM) [K+]o using the whole-cell-clamp technique. 2. Hyperpolarizing clamp pulses from 0 mV induced an instantaneous current jump (I-V relation linear) followed by a time-dependent increase in inward current to a peak, whereas depolarizing clamp pulses induced little outward current. The peak I-V relation showed a strong inward rectification. The inwardly rectifying current was blocked by E-4031. 3. The inward K+ current induced by hyperpolarizing clamp pulses from 0 mV relaxed after reaching its peak. The rate of the relaxation increased as the membrane potential became more negative and concentrations of external Ca2+ or Mg2+ were increased. The steady-state current was smaller as the relaxation of the current accelerated on increasing [Ca2+]o or [Mg2+]o. 4. Depolarizing clamp pulses from -80 mV induced an increase in inward current, reaching a steady state. The amplitude of the steady-state current became smaller and the rate of current increase became slower as [Ca2+]o or [Mg2+]o was increased. 5. The effects of Ca2+ and Mg2+ are well explained by a time- and voltage-dependent blockade of the K+ channel by these ions. The fractional electrical distance of the binding site calculated from the voltage dependence of the blocking rate constant is 0.69 for Ca2+ and 0.88 for Mg2+. The blocking rate constant at 0 mV for Ca2+ is about 15 times faster than that for Mg2+, indicating stronger effects of Ca2+. 6. A re-interpretation of IK in sino-atrial node cells is proposed: there are two independent gates (an activation gate which opens on hyperpolarization and an inactivation gate which closes on hyperpolarization) and a binding site for Ca2+ and Mg2+ inside the channel. Binding of these ions, which is facilitated by hyperpolarization, causes channel blockade, resulting in the observed voltage dependence of IK in physiological concentrations of Ca2+ and Mg2+.

Animals↗
PubMed1996

Sulfhydryl redox modulates ATP-sensitive K+ channels in rabbit ventricular myocytes.

The properties of sulfhydryl redox modulation of the ATP-sensitive K+ K(ATP) channel have been examined in rabbit ventricular myocytes, using the patch-clamp technique. The sulfhydryl oxidizing agent 5.5'-dithio bis-(2-nitro-benzoic acid) (DTNB) induced an inhibition of the channel activity without change in the single channel conductance. DTNB had no effect on the inhibitory action by ATP. Analysis of the open and closed time distributions showed that DTNB decreased the life time of bursts and increased the interburst interval without changes in open and closed time distributions shorter than 5 ms. N-ethylmaleimide (NEM), a substance that reacts with sulfhydryl groups of cysteine residues in proteins, induced an irreversible closure of the channel. The results suggested that changes in the sulfhydryl redox also modulate K(ATP) channel activity of the K(ATP) channel in rabbit ventricular myocytes.

Adenosine Triphosphate↗
PubMed1996

Blockade of the ATP-sensitive potassium channel by taurine in rabbit ventricular myocytes.

Using patch-clamp techniques, the effects of taurine on properties of ATP-sensitive K+ (KATP) channel of rabbit ventricular myocytes were examined. Intracellular taurine (20 mM) markedly depressed the KATP channel activity. The taurine concentration for half-inhibition (apparent Kd) was 13.5 mM with a Hill coefficient, n, of 1.3. Intracellular taurine caused channel inhibition without affecting channel inhibition by ATP. In control conditions, the ATP concentration for half-inhibition (Ki) and n were 73 microM and 1.2 (n = 6), respectively. In the presence of taurine, Ki and n were 81 microM and 1.3 (n = 6), respectively. Analysis of the open and closed time distributions showed that taurine decreased the life time of bursts and increased the inter-burst interval and/or reduced the number of functional channels. 2,4-Dinitrophenol (DNP) activated KATP channel after a lag period. This lag period was much longer after pretreatment with taurine (6.6 +/- 1.2 min, n = 5) than in the absence of taurine (2.8 +/- 1.5 min, n = 12). When DNP was removed in the bath solution, channel activity showed a gradual reduction with time and this process was facilitated by the presence of external taurine (20 mM). From these results it is suggested that taurine blocks KATP channel activity in dose-dependent manner and the depletion of taurine during myocardial ischemia contribute to the early activation of the KATP channel.

2,4-Dinitrophenol↗
PubMed1996

Risk factors of tracheostomal recurrence after laryngectomy for laryngeal carcinoma.

BACKGROUND: Tracheostomal recurrence after total laryngectomy for laryngeal carcinoma has a poor prognosis. The independent risk factors of tracheostomal recurrence are, however, not well documented. METHODS: This is a multivariate analysis of the risk factors of tracheostomal recurrence after total laryngectomy for 322 laryngeal squamous cell carcinomas. The factors included in the analysis were sex, age, tumor stage, sites of tumor involvement, preoperative airway obstruction, preoperative tracheostomy, extent of surgical resection, radiotherapy, and pathological resection margin. RESULTS: Seventeen (5%) patients developed tracheostomal recurrence. Univariate analysis showed that preoperative airway obstruction, subglottic involvement, and postcricoid extension were significant factors associated with tracheostomal recurrence. Multivariate analysis using logistic regression method showed that both subglottic and postcricoid involvement were independent predisposing factors for tracheostomal recurrence. The tracheostomal recurrence rates were 2% in patients without the risk factor and 10% in patients with the presence of one or both risk factors. CONCLUSIONS: Subglottic and postcricoid involvement were independent risk factors for tracheostomal recurrence.

Adult↗