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Biomedical subjects

W K Ho

Publications and source records attributed to W K Ho.

At least 91 records · Page 5Linked to original sources
PubMed1996

Comprehensive analysis of nodal recurrence of advanced laryngeal carcinoma following surgery.

The problems of nodal recurrence after surgical treatment of T3-4 laryngeal carcinoma were analysed. There were 133 N0 and 66 N+ patients. The 5-year actuarial nodal recurrence rate of N0 patients was 18% and N+ patients was 31%. Nodal recurrence was the commonest site of recurrence. The sites of nodal recurrence of N0 patients were at the level II, III, and IV nodes. Both ipsilateral and contralateral nodal recurrences were common. Of those patients who developed nodal recurrence, 63% patients were feasible for surgical salvage. Surgical salvage with radical neck dissection was the preferred treatment for nodal recurrence with 38% 5-year survival rate. The 'watchful waiting policy' in the management of N0 neck is an acceptable option with eventual nodal failure rate of 10% after surgical salvage. Close follow-up of patients is mandatory for the early detection of surgically salvageable nodal recurrence.

Adult↗
PubMed1996

Primary closure of pharyngeal remnant after total laryngectomy and partial pharyngectomy: how much residual mucosa is sufficient?

After total laryngectomy with or without partial pharyngectomy, the remaining pharyngeal defect can be repaired either by primary closure or with additional tissue, depending on the amount of pharyngeal tissue remnant available. The aim of this study was to determine the minimum width of the pharyngeal remnant that could be safely closed primarily without causing difficulty in swallowing. A total of 52 consecutive patients who underwent total laryngectomy were entered into the study. The relaxed and stretched widths of the pharyngeal remnant were measured after removal of the specimen. The widths of the pharyngeal mucosa ranged from 1.5 to 5.0 cm relaxed (mean, 3.24 cm) and from 2.5 to 8.0 cm stretched (mean, 4.83 cm). All neopharynx was reconstructed by closing the pharynx primarily. Seven of the 52 patients developed recurrent tumor with concomitant dysphagia. Two of the 45 patients without recurrence presented with acute dysphagia from food bolus obstruction, and 1 patient developed benign inflammatory stricture following an episode of fish-bone impaction. The narrowest widths of the pharyngeal remnant in this group of 45 were 1.5 cm relaxed and 2.5 cm stretched. As these patients do not have swallowing difficulty, we conclude that in the absence of tumor recurrence, this amount of residual pharyngeal tissue is sufficient both for primary closure of the pharynx and in restoring swallowing function.

Adult↗
PubMed1996

The effect of taurine on the activation osmolality of the osmosensitive current in single ventricular myocytes of rabbits.

An osmosensitive current was identified in rabbit ventricular cells and the effects of taurine on osmotic stress were examined. The osmosensitive current was measured with the whole-cell patch clamp technique and all known currents were blocked using Ba2+, Cd2+, Ni2+, diltiazem, ouabain, Cs+ and tetraethyl ammonium. When hyposmotic solution (200 mosmol/kg) was applied, the background current increased gradually. This osmosensitive current was dependent on Cl-. When the conductance of the activated current reached three times the control conductance, the osmolality was arbitrarily named the activation osmolality. The activation osmolality was regarded as an indication of cell volume expansion. With 20 mM taurine in the pipette solution, the activation osmolality was lowered significantly. With high [Na+] (32.5 mM) in the pipette solution, the effect of taurine in reducing the activation osmolality was larger than that in low [Na+] (2.5 mM). From these results, we conclude that taurine reduces the activation osmolality and this effect is more pronounced in the presence of high [Na+] in the pipette solution. It is suggested that Na+-dependent taurine transport could be involved in reducing osmotic stress.

Animals↗
PubMed1995

Different modulation of Ca-activated K channels by the intracellular redox potential in pulmonary and ear arterial smooth muscle cells of the rabbit.

We investigated the electrical responses of Ca-activated K (KCa) currents induced by hypoxia and reduction or oxidation of the channel protein in pulmonary (PASMC) and ear (EASMC) arterial smooth muscle cells using the patch-clamp technique. In cell-attached patches, in the presence of a high K solution (containing 0.316 microM Ca2+), the activity of KCa channels from PASMC was decreased (by 49 +/- 7% compared to control, pipette potential = -70 mV) by changing to a hypoxic solution (1 mM Na2S2O4, aeration with 100% N2 gas). EASMC channels did not respond to hypoxia. In order to investigate the possible mechanisms involved, using inside-out patches bathed symmetrically in 150 mM KCl, we applied redox couples to the intracellular side. Reducing agents, such as dithiothreitol (DDT, 5 mM), reduced glutathione, (GSH, 5 mM), and nicotinamide adenine dinucleotide reduced (NADH, 2 mM) decreased PASMC, but not EASMC, KCa channel activity. However, oxidizing agents such as 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB, 1 mM), oxidized glutathione (GSSG, 5 mM) and NAD (2 mM) increased KCa channel activity in both PASMC and EASMC. The increased activity due to oxidizing agents was restored by applying reducing agents. From these results, we could suggest that the basal redox state of the EASMC KCa channel is more reduced than that of the PASMC channel, since the response of KCa channels of the EASMC to intracellular reducing agents differs from that of the PASMC. This difference may be related to the different responses of PASMC and EASMC KCa channels to hypoxia.

Animals↗
PubMed1995

Redox agents as a link between hypoxia and the responses of ionic channels in rabbit pulmonary vascular smooth muscle.

Ca(2+)-activated K+ currents (IK(Ca)) and voltage-dependent Ca(2+)-insensitive K+ currents (IK(V)) were recorded using the patch clamp technique to study the pulmonary (PASMC) and ear arterial smooth muscle cells (EASMC) of the rabbit and the possible regulatory mechanisms related to hypoxia. When a hypoxic solution (1 mM Na2S2O4, gassed with 100% N2) was superfused, the activity of Ca(2+)-activated K+ channels (KCa channels) recorded at a pipette potential of -70 mV in cell-attached mode was decreased to 49 +/- 7% in PASMC, whereas EASMC KCa channels did not respond to hypoxia. In inside-out patches (bathed symmetrically in 150 mM KCl), reducing agents such as dithiothreitol (DTT; 5 mM), reduced glutathione (GSH; 5 mM) and NADH (2 mM) decreased KCa channel activity in PASMC, but they did not affect the EASMC KCa channel. However, oxidizing agents such as 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB; 1 mM), oxidized GSH (GSSG; 5 mM) and NAD (2 mM) increased KCa channel activity in both PASMC and EASMC. In the whole-cell configuration, using a pipette solution containing a high concentration of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA; 10 mM), PASMC IK(V) were activated by depolarizing step pulses to voltages more positive than -30 mV (holding potential, -80 mV). IK(V) was increased by application of a membrane-permeable oxidizing agent, 2,2'-dithio-bis(5-nitropyridine) (DTBNP; 200 microM), whereas it was decreased by application of DTT (5 mM). From these results, it could be suggested that hypoxic pulmonary vasoconstriction is attributable, at least in part, to a change of cellular redox state, which decreases outward K+ currents. This hypothesis is further supported by the observation that the basal redox state of EASMC KCa channels is more reduced than that of PASMC KCa channels. The distinct responses to hypoxia of pulmonary and systemic arterial smooth muscle could be explained by this difference.

Animals↗
PubMed1994

Effects of adriamycin on ionic currents in single cardiac myocytes of the rabbit.

Adriamycin has been widely used as an anticancer drug, but its clinical use is limited by a dose-dependent cardiac toxicity. Proposed mechanisms for the adriamycin-induced cardiomyopathy include increasing the Ca current, inhibiting the Na/Ca exchange and dysfunction of the sarcoplasmic reticulum (SR). Using the whole cell voltage clamp technique in single isolated atrial and ventricular myocytes of the rabbit, we have investigated the effect of adriamycin on various current systems which are related to regulating intracellular Ca concentration: the Ca current, the Na/Ca exchange current and [Ca2+]i-dependent currents (ouabain-induced transient inward current and the inward tail current). Adriamycin, 0.05 mg/ml, increased Ca current (L-type) by 61%. Adriamycin inhibited the inward tail current in a dose-dependent manner between 0.02 and 0.1 mg/ml and when low concentration was used the effect was reversible. Ouabain-induced transient inward current was also suppressed by 0.05 mg/ml adriamycin. Na/Ca exchange current which is partly responsible for inducing [Ca2+]i-dependent currents was, however, not affected by adriamycin, suggesting that the effect adriamycin on [Ca2+]i-dependent currents is due to inhibition of SR function. From these results it is suggested that the increase of Ca current and inhibition of SR function cause adriamycin-induced cardiac toxicity: SR dysfunction not only causes a decrease of myocardial contractility, it can also accelerate the Ca overload process which might originate from the increase of Ca current.

4-Aminopyridine↗
PubMed1994

High selectivity of the i(f) channel to Na+ and K+ in rabbit isolated sinoatrial node cells.

The ionic selectivity of the hyperpolarization-activated inward current (i(f)) channel to monovalent cations was investigated in single isolated sinoatrial node cells of the rabbit using the whole-cell patch-clamp technique. With a 140 mM K+ pipette, replacement of 90% external Na+ by Li+ caused a -24.5 mV shift of the fully activated current/voltage I/V curve without a significant decrease of the slope conductance. With a 140 mM Cs+ pipette, the i(f) current decreased almost proportionally to the decrease in external [Na+]o as Li+ was substituted. These responses are practically the same as those observed with N-methyl glucamine (NMG+) substitution, suggesting that the relative permeability of Li+ compared with Na+ for the i(f) channel is as low as that of NMG+. When Cs+ or Rb+ was substituted for internal K+, the fully activated I/V relationship for i(f) showed strong inward rectification with a positive reversal potential, indicating low permeability of the i(f) channel for Cs+ and Rb+. These results show that the i(f) channel is highly selective for Na+ and K+ and will not pass the similar ions Li+ and Rb+. Such a high degree of selectivity is unique and may imply that the structure of the i(f) channel differs greatly from that of other Na+ and K+ conducting channels.

Animals↗
PubMed1993

Hypothermia, hyperhidrosis, myokymia and increased urinary excretion of catecholamines associated with a thymoma.

OBJECTIVE: To report a rare syndrome associated with a thymoma and its first successful treatment with gammaglobulin. CLINICAL FEATURES: A 49-year-old white male presented with marked hypothermia, hyperhidrosis, myokymia and increased urinary excretion of catecholamines four weeks after complete excision of a malignant thymoma. He became increasingly drowsy, obtunded and required ventilatory support. INTERVENTION AND OUTCOME: A catecholamine secreting tumour was excluded and he was treated with intravenous gammaglobulin for five days, with dramatic improvement in his condition. Six months later he remains in remission. CONCLUSION: The response to treatment in this patient suggests an immunological pathogenesis for this rare group of symptoms associated with a thymoma.

Catecholamines↗
PubMed1993

Internal K ions modulate the action of external cations on hyperpolarization-activated inward current in rabbit isolated sinoatrial node cells.

We have investigated the effect of change in external Na+ concentration on the hyperpolarization-activated inward current (I(f)) in the presence of different internal cations. Rabbit single isolated sinoatrial node cells were studied using the whole-cell patch-clamp technique. With 140 mM K+ pipettes, lowering [Na+]o causes the fully activated I/V curve for I(f) to shift in a negative direction without a significant decrease of the slope conductance. The PNa/PK ratio, as defined by the Goldman-Hodgkin-Katz equation, is concentration-dependent: the lower the [Na+]o, the higher PNa/PK. The conductance/concentration relationship for I(f) shows saturation at low [Na+]o or [K+]o, indicating that the channel has a strong affinity for external cations. With 140 mM Cs+ pipettes, the I/V curve shows strong inward rectification and inward I(f) current decreases almost proportionally to the decrease in [Na+]o; the conductance/concentration relationship for I(f) shifts to the right suggesting that the binding affinity of the external binding site is reduced. These results suggest that the I(f) channel is a multi-ion channel with a high-affinity external binding site, the affinity of which is modulated by internal cations.

Animals↗
PubMed1993

Immunological relatedness of ribosome-inactivating proteins from the Cucurbitaceae family.

The immunological relatedness of various ribosome-inactivating proteins (RIPs) from the Cucurbitaceae family was examined using enzyme-linked immunosorbent assay (ELISA). The proteins studied included trichosanthin (TCS), beta-trichosanthin (beta-TCS), alpha-momorcharin (alpha-MMC), beta-momorcharin (beta-MMC), momorcochin (MCC), luffaculin (LFC) and Mirabilis antiviral protein (MAP). In general, an antigen exhibited the highest immunoreactivity in an assay using it own antibodies when compared with others RIPs, and MAP demonstrated the lowest immunoreactivity in most ELISAs employing antibodies raised against the other RIPs. LFC also exhibited very low immunoreactivity in most assays, TCS and beta-TCS are immunologically disparate in a number of ELISAs. alpha-MMC and beta-MMC are immunologically related but not identical. MCC manifested immunological relatedness to the momorcharins to a certain extent.

Animals↗
PubMed1992

Extranodal Rosai-Dorfman disease: an uncommon cause of persistent nodule in the ear.

A 40-year-old woman presented with a nodule over the tragus of the right ear. A biopsy was initially reported as showing non-specific inflammation. In view of the persistence of the lesion, the histological material was reviewed, leading to revision of the diagnosis to Rosai-Dorfman disease, a diagnosis further confirmed by immunoreactivity of the histiocytes for S-100 protein. This case represented the extranodal form of Rosai-Dorfman disease in the absence of lymph node involvement.

Adult↗
PubMed1991

Effects of Ca(2+)-buffer concentration and stimulus interval on the voltage dependence and timecourse of calcium-release-dependent inward current in rabbit atrial myocytes.

To investigate the kinetics of the inward Na-Ca exchange tail current activated by internal calcium in rabbit atrial cells, the whole-cell patch-clamp technique with intracellular perfusion was used. We recorded the inward phase of this current during repolarizations following a brief 2-5 ms depolarizing pulse to +40 mV from a holding potential of -70 mV. Peak activation of the current occurs about 10 ms from the beginning of the depolarizing pulse, and it decays spontaneously with a slow timecourse. The voltage dependence of the process that activates the inward current from -40 mV to +40 mV has a very steep slope between -40 and -20 mV and then virtually saturates between -10 mV and +40 mV. The voltage dependence of the process that activates the inward current is steeper than that which activates the sarcolemmal calcium current, iCa.L, and the timecourse of the current relaxation is much slower at low-frequency stimulation and when using low concentrations of Ca-buffer. The magnitude and timecourse of the calcium transients estimated by the inward tail current are smaller and faster, and the slow component of decay was abolished by the presence of high intracellular concentrations of Ca-buffer or by high frequency stimulation. These observations suggest that calcium release from the sarcoplasmic reticulum may be triggered by only a small fraction of the sarcolemmal calcium current.

Animals↗
PubMed1991

Cloning and sequencing of the grass carp (Ctenopharyngodon idellus) growth hormone gene.

An enriched lambda gt11 library for screening the grass carp (Ctenopharyngodon idellus) growth hormone gene was constructed using HindIII digested genomic DNA extracted from the spleen of the fish. Probing this library with a homologous cDNA, a clone carrying the growth hormone gene was obtained. The gene is 2501 bp long and consists of five exons and four introns. The sequence of nucleotide in the exons is almost identical to that of the cDNA except for ten positions. Analysis of the 5' sequence up to 1220 bp from the +1 position reveals the presence of a TATA box as well as a number of consensus regulatory sequences. Comparison of the grass carp growth hormone gene with those of other fish indicates that there is a high degree of homology with the gene from the common carp but not with those from the rainbow trout and Atlantic salmon.

Animals↗
PubMed1991

Activation and inhibition of human alcohol dehydrogenase by monoclonal antibodies.

The human class I alcohol dehydrogenase isozyme beta 2 beta 2 was used as the antigen to raise monoclonal antibodies. Altogether seven lines of hybridomas secreting monoclonal antibodies were obtained. None of the antibodies was isozyme specific and all of them exhibited a similar affinity against all isozymes of the human class I ADH. Five out of the seven monoclonal antibodies had no effect on beta 2 beta 2 activity. Antibody G3 acted as a non-competitive inhibitor with a KI of 3 micrograms/ml at pH 7.5. Increasing pH was effective in reducing the level of inhibition. On the other hand, antibody 1D4 exhibited a pH-dependent activation of ADH activity. In the presence of this antibody, the pH optimum of beta 2 beta 2 was shifted from 9 to 8.5 and total activity was increased by 70% at this optimal pH. Kinetic analysis indicates that 1D4 probably acts as a non-competitive activator and may exert its action by interacting with the coenzyme binding site.

Alcohol Dehydrogenase↗
PubMed1991

Cloning of the cDNA of alpha-momorcharin: a ribosome inactivating protein.

Using a lambda gt11 cDNA library constructed from the seeds of the bitter melon (Momordica charantia), we have obtained a full length cDNA containing the entire sequence of alpha-momorcharin by immunoscreening. The length of this cDNA is 1044 basepairs long and it consists of an open reading frame coding for a polypeptide of 286 amino acids. The first 23 residues of this polypeptide probably code for a signal sequence. The N-terminal sequence of the deduced protein is exactly identical to that determined by peptide sequencing. The sequence identity between alpha-momorcharin and other ribosome inactivating proteins, such as trichosanthin and ricin A chain, is high, i.e., 34-63%. Examination of the predicted secondary structure of alpha-momorcharin and trichosanthin indicates that these proteins have regions of high structural similarities and this may account for the common biological activities that they share, viz., abortificant, immunosuppressive, antitumor and inhibition of HIV-1.

Amino Acid Sequence↗