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Biomedical subjects

P S Wong

Publications and source records attributed to P S Wong.

At least 19 recordsLinked to original sources

Event-related brain correlates of associative learning without awareness.

Controversy exists about whether associative learning occurs without awareness. In an earlier study using subthreshold (subliminal) stimuli, we reported evidence that such learning could occur as measured by event-related brain potentials [ERP; Cons. Cognit. 6 (1997) 519]. In the present study, we extend these findings by changing several aspects of the methodology in order to provide a more stringent test of this effect and to examine its generality. We used two matched words (murder and cancer) as conditional stimuli (CS); a 100 dB white noise blast as unconditional stimulus (US); a CS-US interval of 3 s; and a full-factorial design with CSs counterbalanced. The conditioning-acquisition phase occurred when the CSs were perceptually unconscious, as confirmed by a subsequent behavioral task. The conditioning-acquisition and postconditioning-extinction phases were examined for ERP evidence of associative learning. The clearest and strongest evidence for associative learning without awareness was observed in the ERP component measures (up to 1 s, poststimulus) in the postconditioning-extinction phase. The CS+ was significantly more positive than the CS- in the P3b-LP component region, which is highly consistent with the results of our earlier study. Differences also were observed in the P1-P2 components. In an unexpected finding, we observed a significant positive slow potential shift for the CS+ in the region between 1 and 3 s poststimulus. We discuss these results and their implications for our understanding of associative learning and awareness.

Adult↗

Dynamic variations in affective priming.

The present study investigates the dynamics of emotional processing and awareness using an affective facial priming paradigm in conjunction with a multimodal assessment of awareness. Key facial primes are visually masked, and are presented for brief (unconscious) and extended (conscious) durations. Using a preference measure, we examine whether the effects of the primes differ qualitatively (Murphy & Zajonc, 1993). We show that: (a) unconscious affective priming with faces emerges strongly in initial presentations and diminishes rapidly with repetition; (b) conscious affective priming also emerges strongly in initial presentations, however it persists in strength with repetition; and (c) in contrast to other reports on the salience of negative stimuli, happy faces appear more salient than sad faces when presented outside awareness. We discuss the limits and extensions of unconscious affective priming with faces, and consider several methodological and conceptual questions concerning emotional processing out of awareness.

Adolescent↗

Inactivation of glutathione S-transferases by nitric oxide-derived oxidants: exploring a role for tyrosine nitration.

Reactive intermediates derived from nitric oxide ((*)NO) are thought to play a contributing role in disease states associated with inflammation and infection. We show here that glutathione S-transferases (GSTs), principal enzymes responsible for detoxification of endogenous and exogenous electrophiles, are susceptible to inactivation by reactive nitrogen species (RNS). Treatment of isolated GSTs or rat liver homogenates with either peroxynitrite, the myeloperoxidase/hydrogen peroxide/nitrite system, or tetranitromethane, resulted in loss of GST activity with a concomitant increase in the formation of protein-associated 3-nitrotyrosine (NO(2)Tyr). This inactivation was only partially (<25%) reversible by dithiothreitol, and exposure of GSTs to hydrogen peroxide or S-nitrosoglutathione was only partially inhibitory (<25%) and did not result in protein nitration. Thus, irreversible modifications such as tyrosine nitration may have contributed to GST inactivation by RNS. Since all GSTs contain a critical, highly conserved, active-site tyrosine residue, we postulated that this Tyr residue might present a primary target for nitration by RNS, thus leading to enzyme inactivation. To directly investigate this possibility, we analyzed purified mouse liver GST-mu, following nitration by several RNS, by trypsin digestion, HPLC separation, and matrix-assisted laser desorption/ionization-time of flight analysis, to determine the degree of tyrosine nitration of individual Tyr residues. Indeed, nitration was found to occur preferentially on several tyrosine residues located in and around the GST active site. However, RNS concentrations that resulted in near complete GST inactivation only caused up to 25% nitration of even preferentially targeted tyrosine residues. Hence, nitration of active-site tyrosine residues may contribute to GST inactivation by RNS, but is unlikely to fully account for enzyme inactivation. Overall, our studies illustrate a potential mechanism by which RNS may promote (oxidative) injury by environmental pollutants in association with inflammation.

Animals↗

Identification and determination of nucleosides in rat brain microdialysates by liquid chromatography/electrospray tandem mass spectrometry.

A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method has been developed for the determination of brain basal nucleosides (inosine, guanosine and adenosine) in microdialysates from the striatum and cortex of freely moving rats. A microdialysis probe was surgically implanted into the striatum or cortex of individual rats and Ringer's solution was used as the perfusion medium at a flow rate of 0.3 or 0.5 microl/min. The samples were then analyzed off-line by LC/MS/MS experiments. The separation of inosine, guanosine and adenosine was carried out on a cyano column using a mobile phase of 10 mM ammonium acetate, 1% acetic acid and 8% methanol at a flow rate of 0.4 ml/min. Analytes were detected by electrospray ionization tandem mass spectrometry in the positive ion mode. The detection limit for inosine, guanosine and adenosine was 80, 80 and 40 pg on column, respectively. With this method, the intercellular basal inosine, guanosine and adenosine concentrations in striatum and cortex of rat were determined.

Animals↗

Renal cell carcinoma and malignant phase hypertension.

Many cross-sectional and follow-up studies of large numbers of patients with hypertension have demonstrated an increased prevalence and mortality from renal cancer. We report the details of three patients with renal cell carcinoma from a series of 254 consecutive patients with malignant phase hypertension, an excess over the expected number reported from several large published series with non-malignant hypertension. In view of this excess we investigated the prevalence of hypertension in a series of 192 consecutive patients who presented with a diagnosis of renal cell carcinoma, in comparison with a local unselected population screening survey. Hypertension was found in 43% of the renal carcinoma patients and 20% of the local population, also a clear excess. The mechanism of the association between renal cancer and malignant and non-malignant hypertension is unclear.

Adult↗

Inactivation of creatine kinase by S-glutathionylation of the active-site cysteine residue.

Protein S-thiolation, the formation of mixed disulphides of cysteine residues in proteins with low-molecular-mass thiols, occurs under conditions associated with oxidative stress and can lead to modification of protein function. In the present study, we examined the site of S-thiolation of the enzyme creatine kinase (CK), an important source of ATP in myocytes. Inactivation of this enzyme is thought to play a critical role in cardiac injury during oxidative stress, such as during reperfusion injury. Reaction of rabbit CK M isoenzyme with GSSG, used to model protein S-thiolation, was found to result in enzyme inactivation that could be reversed by GSH or dithiothreitol. Measurement of GSH that is released during the thiolation reaction indicated that the maximum extent of CK thiolation was approx. 1 mol of GSH/mol of protein, suggesting thiolation on one reactive cysteine residue. Accordingly, matrix-assisted laser-desorption ionization MS confirmed that the molecular mass of CK was increased, consistent with addition of one GSH molecule/molecule of CK. Using trypsin digestion, HPLC and MS analysis, the active-site cysteine residue (Cys(283)) was identified as the site of thiolation. Reversal of thiolation was shown to be rapid when GSH is abundant, rendering dethiolation of CK thermodynamically favoured within the cell. We conclude that S-glutathionylation of CK could be one mechanism to explain temporary reversible loss in activity of CK during ischaemic injury. The maintainance of GSH levels represents an important mechanism for regeneration of active CK from S-glutathionylated CK.

Amino Acid Sequence↗

In vivo microdialysis and reverse phase ion pair liquid chromatography/tandem mass spectrometry for the determination and identification of acetylcholine and related compounds in rat brain.

A method using liquid chromatography/tandem mass spectrometry (LC/MS/MS) has been developed for the determination of basal acetylcholine (ACh) in microdialysate from the striatum of freely moving rats. A microdialysis probe was surgically implanted into the striatum of the rats and Ringer's solution was used as the perfusion medium at a flow rate of 2 microL per minute. The samples were then analyzed off-line by LC/MS/MS experiments. The separation of ACh and choline (Ch) was carried out using reverse phase ion pair liquid chromatography with heptafluorobutyric acid as a volatile ion pairing reagent. Analytes were detected by electrospray ionization tandem mass spectrometry in the positive ion mode. The detection limit for ACh was 1.4 fmol on column, which is at least three times lower than previously reported. Three quaternary ammonium compounds in the rat brain microdialysate were also identified by tandem mass spectrometry experiments in which the unknown mass spectra were compared with standard reference compounds. These compounds were identified as carnitine, acetylcarnitine and (3-carboxypropyl)trimethylammonium. This is the first known report of the compound (3-carboxypropyl)trimethylammonium being found in rat brain.

Acetylcholine↗

Pneumonia presenting as acute abdomen in children: a report of three cases.

From 10th September 1998 till 5th June 1999, the Paediatric and Cardiothoracic Surgery Units of Sultanah Aminah Hospital Johor Bahru managed three children with lung collapse secondary to pneumonia. The dominant initial clinical presentation in all three cases was acute abdominal pain. Basal pneumonia was diagnosed in two cases post-operatively after surgical contributory causes were excluded intra-operatively. Thoracotomy, evacuation of infected debris and decortication of the collapsed lung was done in all three cases. In children presenting with acute abdominal pain, basal pneumonia should be considered as a possible contributory cause.

Abdomen, Acute↗

Effect of acute saline volume loading on renal sympathetic nerve activity in anaesthetised fructose-fed and fat-fed rats.

Experiments were conducted to investigate the effects of activation of cardiopulmonary vagal afferent nerve endings by acute saline volume expansion on sympathetic efferent renal nerve activity in anaesthetised fat-fed and fructose-fed Wistar rats. Four weeks of fat feeding caused obesity in the Wistar rats which was associated with a mild elevation in blood pressure (118 +/- 4 mmHg vs. 105 +/- 1 mmHg in the lean control rats, P < 0.05). Fructose feeding in Wistar rats for 4 weeks also elicited an elevation of blood pressure (113 +/- 4 mmHg, P < 0.05) and plasma glucose levels (6.3 +/- 0.3 mmol/l vs. 4.0 +/- 0.3 mmol/l lean control rats, P < 0.01). The fat-fed rats displayed a higher basal renal sympathetic nerve activity (RSNA) value when compared with the lean rats (3.9 +/- 0.4 mV/s vs. 2.8 +/- 0.4 mV/s, P < 0.05) whereas the RSNA levels were similar in all the other rat groups. The power spectral analysis of RSNA showed the basal values of percentage power at heart rate frequency were significantly higher in Wistars fed ad lib (P < 0.01), rats fed on fructose for 2 or 4 weeks (P < 0.01 and P < 0.05, respectively) and fat-fed rats (P < 0.01) when compared to the lean diet-controlled rats. Acute volume expansion (10% body wt) over 40 min caused efferent renal sympatho-inhibition in all the animal groups. The pattern and magnitude of response in MAP, RSNA, and power spectral analysis parameters to the volume expansion were similar in the lean control rats, the Wistar and fructose fed rats but was greater in the fat-fed rats (P < 0.05) as compared to the lean control rat. The profile of the reduction in percentage power at heart rate frequency to volume expansion was greater (P < 0.05) in the fat-fed rat than in the lean control rats. The present data demonstrates that the reflex efferent renal sympatho-inhibition to volume expansion was impaired in the diet-induced obese rat but not in the fructose fed rats. This suggests that a defect in the neuro-humoral regulation of kidney control of extracellular fluid volume is present which may contribute to the mild hypertension in the obese rat.

Anesthesia↗

In vivo microdialysis/liquid chromatography/tandem mass spectrometry for the on-line monitoring of melatonin in rat.

Liquid chromatography/tandem mass spectrometry (LC/MS/MS) has been coupled to in vivo microdialysis for on-line monitoring of melatonin in a freely moving rat for a period of 15 hours. A microdialysis probe was surgically implanted into the jugular vein of the rat, and deionized water was used as the perfusion medium at a flow rate of 1.0 microL/min. Microdialysis samples were collected in an on-line injector with sample injection every 30 minutes. Melatonin was dosed by intraperitoneal (i.p.) injection and then monitored by microdialysis/LC/MS/MS. The whole experiment, including the microdialysis sampling and sample injection into the LC/MS system, was fully automated. Metabolites of melatonin were identified off-line by LC/MSn experiments. Two metabolites were identified as 6-hydroxymelatonin and cyclic 2-hydroxymelatonin, consistent with ones found previously in the literature.

Animals↗

Management of pulmonary thrombo-embolism using catheter manipulation: a report of four cases and review of the literature.

To date the management of pulmonary thrombo-embolism is still largely limited to anticoagulation. Heparin and oral anticoagulation have been shown to be effective in reducing recurrence and death in venous thrombo-embolism. During the acute stage, systemic thrombolytic therapy has also been advocated for the rapid dissolution of the thrombus in patients with haemodynamic instability. We describe four patients with acute pulmonary thrombo-embolism who were managed with catheter-based thrombus manipulation with intrapulmonary thrombolysis. This management strategy should be considered in patients with pulmonary thrombo-embolism who continue to deteriorate despite conventional management with anticoagulation or systemic thrombolysis.

Adolescent↗

Anxiety, signal anxiety, and unconscious anticipation: neuroscientific evidence for an unconscious signal function in humans.

A central tenet of psychoanalysis, and arguably of any comprehensive theory of mind, is the existence of a psychological unconscious. Years of clinical investigation into the nature of unconscious processes have facilitated the development of psychoanalysis as a clinical method. Empirical investigations of unconscious mental processes, however, have lagged behind clinical inquiry. With few exceptions, attempts to understand unconscious processes using rigorous experimental controls have remained sequestered in scientific domains other than psychoanalysis, where they have proliferated recently. In view of this recent upsurge of research on unconscious processes outside of psychoanalysis, efforts to integrate such knowledge into general theories of psychopathology and clinical investigation are critical. In this paper, an interdisciplinary approach is taken to the study of one aspect of unconscious mental functioning--what Freud originally termed signal anxiety. Signal anxiety is examined using information from cognitive psychology and learning theory, psychophysiology, behavioral neuroscience, and psychoanalytic theory. Though the original concept of signal anxiety is supported by recent research, it is concluded that signal anxiety is probably best thought of not as the affect of anxiety but as a subset of unconscious mental processes that have a signal function of anticipating danger. Such unconscious anticipatory processes are a general feature of the mind that includes responses to both real and imagined (neurotic) appraisals of a situation. The neurophysiological structures and processes associated with unconscious anticipation in humans are just beginning to be understood.

Anxiety↗

Reaction of organic nitrate esters and S-nitrosothiols with reduced flavins: a possible mechanism of bioactivation.

Organic nitrate esters, such as glyceryl trinitrate and isosorbide dinitrate, are a class of compounds used to treat a variety of vascular ailments. Their effectiveness relies on their ability to be bioactivated to nitric oxide (NO) which, in turn, relaxes vascular smooth muscle. Although there have been many biological studies that indicate that NO can be formed from organic nitrate esters in a biological environment, the chemical mechanism by which this occurs has yet to be established. Previous studies have implicated both flavins and thiols in organic nitrate ester bioactivation. Thus, we examined the chemical interactions of flavins and thiols with organic nitrate esters as a means of determining the role these species may play in NO production. Based on these studies we concluded that a reasonable chemical mechanism for organic nitrate ester bioactivation involves reduction to the organic nitrite ester followed by conversion to a nitrosothiol. The release of NO from nitrosothiols can occur via a variety of processes including reaction with dihydroflavins and NADH.

Biotransformation↗

Multiple coronary artery bypass grafting in dextrocardia: case report.

This is a case report of an unusual case of a patient with dextrocardia and "situs inversus totalis" who presented with unstable angina. Coronary angiography revealed severe main stem and severe triple vessel coronary artery disease. The patient later underwent successful emergency coronary artery bypass graft surgery. To the authors' knowledge this is the first reported case in Malaysia and also, the first ever report in the literature of multiple vessel coronary artery grafting, including the use of the right internal mammary artery.

Aged↗

Traumatic herniation of the heart into the right hemithorax.

Pericardial rupture after blunt chest trauma is described in the literature. This case report summarises our experience with a 22-year old male patient who suffered blunt chest trauma during a motor vehicle accident. On admission no serious injuries could be detected, but 3 hours later, displacement of the heart to the right hemithorax combined with sudden cardiac failure appeared. Emergency thoracotomy revealed a right-sided rupture of the pericardium with complete herniation of the heart into the right pleural cavity and consequent strangulation by the margins of the pericardial defect.

Accidents, Traffic↗