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P W Wong

Publications and source records attributed to P W Wong.

At least 19 recordsLinked to original sources
PubMed2002

Identification and characterization of C6orf37, a novel candidate human retinal disease gene on chromosome 6q14.

We have identified a novel human gene, chromosome 6 open reading frame 37 (C6orf37), that is expressed in the retina and maps to human chromosome 6q14, a genomic region that harbors multiple retinal disease loci. The cDNA sequence contains an open reading frame of 1314 bp that encodes a 437-amino acid protein with a predicted molecular mass of 49.2 kDa. Northern blot analysis indicates that this gene is widely expressed, with preferential expression observed in the retina compared to other ocular tissues. The C6orf37 protein shares homology with putative proteins in R. norvegicus, M. musculus, D. melanogaster, and C. elegans, suggesting evolutionary conservation of function. Additional sequence analysis predicts that the C6orf37 gene product is a soluble, globular cytoplasmic protein containing several conserved phosphorylation sites. Furthermore, we have defined the genomic structure of this gene, which will enable its analysis as a candidate gene for chromosome 6q-associated inherited retinal disorders.

Amino Acid Sequence↗
PubMed2002

The frequency of pre-core gene mutations in chronic hepatitis B infection: a study of Malaysian subjects.

A retrospective study was carried out to determine the frequency of the pre-core stop codon mutant virus in a group of chronic hepatitis B carriers: 81 cases were considered [33 hepatits B e antigen (HBe) positive and 48 HBe negative]. All of the HBe positive cases had detectable viral DNA by hybridization analysis; in the case of the HBe negative cases, one third had detectable viral DNA by hybridization analysis and two thirds had HBV DNA detectable by polymerase chain reaction (PCR) amplification. Pre-core stop codon mutant detection was carried out on all specimens using allele-specific oligonucleotide hybridization following PCR amplification of the target sequence. The pre-core mutant was detected in 13/33 (39.4%) of HBe positive cases and in 32/48 (66.7%) of HBe negative cases. Sequence analysis was carried out on 8 of the 16 HBe negative specimens that did not carry the pre-core mutant virus to determine the molecular basis for the HBe minus phenotype in these cases: the 1762/1764 TA paired mutation in the second AT rich region of the core promoter was detected in five cases; a start codon mutation was detected in one case. The predominant mutation resulting in the HBe minus phenotype in our isolates was the 1896A pre-core ("pre-core stop codon") mutation; other mutations responsible for the phenotype included the core promoter paired mutation and pre-core start codon mutation. In view of the high frequency of the pre-core mutant virus, sequence analysis was performed to determine the virus genotype on the basis of the nucleotide sequence of codon 15. The sequences of 21 wild type virus (14 HBe positive and 7 HBe negative cases) were examined: 15 were found to be codon 15 CCT variants (71.4%); the frequency in the HBe positive group was 12/14 (85.7%), while that in the HBe negative group was 3/7 (42.9%). The high frequency of the codon 15 CCT variant in association with the frequent occurrence of the pre-core mutant in our isolates concurs with the results of other studies.

Base Sequence↗
PubMed2001

Nutritional support in critically ill patients with cancer.

Nutritional depletion is a common problem seen in critically ill patients with cancer and is associated with increased morbidity and mortality. Infection and injury activate a cascade of metabolic events that leads to a poor nutritional state and wasteful energy consumption. The goals of nutritional support entail minimizing starvation, preventing nutrient deficiencies, supporting or improving immune function, and facilitating tissue repair and wound healing. Further understanding of the metabolic changes of illness will improve effective regulation of the inflammatory events occurring in critically ill patients. Multiple clinical parameters are available to assess the nutritional status in critically ill patients, but no standard recommendations can be made at this time. The use of these parameters can be appropriate, provided that their limitations are understood clearly. The development and standardization of objective parameters to identify patients at risk or with subclinical malnutrition are needed. Enteral and parenteral feedings are safe and effective methods to deliver nutrients to critically ill patients with cancer who are unable to ingest adequate amounts orally. Early nutritional support should be instituted in the appropriate clinical setting. Specialized nutritional solutions and supplements require careful consideration in patients with renal, hepatic, cardiac, or pulmonary disorders. The unselective use of nutritional support is not indicated in well-nourished patients with cancer undergoing surgery, chemotherapy, or radiotherapy in whom adequate oral intake is anticipated. Nutritional support remains an important adjunctive therapy in the overall management of critically ill patients. Continued clinical investigations in nutrition are necessary to identify other groups of patients who can benefit from nutritional interventions.

Critical Illness↗
PubMed2001

A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy.

Stargardt-like macular dystrophy (STGD3, MIM 600110) and autosomal dominant macular dystrophy (adMD) are inherited forms of macular degeneration characterized by decreased visual acuity, macular atrophy and extensive fundus flecks. Genetic mapping data suggest that mutations in a single gene may be responsible for both conditions, already known to bear clinical resemblance. Here we limit the minimum genetic region for STGD3 and adMD to a 0.6-cM interval by recombination breakpoint mapping and identify a single 5-bp deletion within the protein-coding region of a new retinal photoreceptor-specific gene, ELOVL4, in all affected members of STGD3 and adMD families. Bioinformatic analysis of ELOVL4 revealed that it has homology to a group of yeast proteins that function in the biosynthesis of very long chain fatty acids. Our results are therefore the first to implicate the biosynthesis of fatty acids in the pathogenesis of inherited macular degeneration.

Amino Acid Sequence↗
PubMed2001

ortho-substituted PCB95 alters intracellular calcium signaling and causes cellular acidification in PC12 cells by an immunophilin-dependent mechanism.

ortho-Substituted PCBs mobilize Ca2+ from isolated brain microsomes by interaction with FKBP12/RyR complexes. Investigation into the cellular importance of this mechanism was undertaken using PC12 cells by fluoroimaging the actions of specific PCB congeners on [Ca2+]i and pH. RyR and IP3R share a common intracellular Ca2+ store in PC12 cells. Perfusion of nM to low microM PCB95 caused a transient rise of [Ca2+]i that was not completely dependent on extracellular Ca2+. Pre-incubation of the cells with ryanodine or FK506 completely eliminated PCB95 responses, suggesting a primary action on the FKPP12/RyR-sensitive store. PCB95, but not PCB126, induced a gradual decrease in cytosolic pH that could be completely eliminated by FK506 pre-incubation of the cells. Direct respiration measurement using isolated brain mitochondria demonstrated that neither of the PCBs directly altered any stage of mitochondrial respiration. These results revealed that PCB95 disrupts intracellular Ca2+ signaling in PC12 cells by interaction with the FKBP12/RyR complex that in turn accelerated cellular metabolism, possibly affecting signaling between ER and mitochondria. Since ortho-substituted PCBs have been shown to be neurotoxic and may affect neurodevelopment, studies on the molecular mechanism by which they alter cellular signaling may provide valuable information on the physiological roles of FKPB12 and RyR on neuronal functions.

Acidosis↗
PubMed2000

Antithrombotic and hemostatic capacity of factor Xa versus thrombin inhibitors in models of venous and arteriovenous thrombosis.

Thrombin plays a central role in venous and arterial thrombosis. We utilized two different rabbit models of in vivo thrombosis to investigate the effect of inhibitors of thrombin generation and thrombin activity. The agents tested were specific inhibitors of factor Xa (fXa) [N2-[(phenylmethyl)sulfonyl]-D-arginyl-N-[(1S)-4-[(aminoiminomethyl++ +)a mino]-1-(2-thiazolylcarbonyl)butyl]-glycinamide (C921-78)] and thrombin [D-phenylalanyl-N-[4-[(aminoiminomethyl)amino]-1-(chloroacetyl)but yl]-L-prolinamide (PPACK)], as well as drugs that affect both thrombin and fXa, unfractionated and low molecular weight (enoxaparin) heparin. The agents administered as constant intravenous infusion were evaluated for antithrombotic efficacy in anesthetized rabbits. All four agents were capable of dose dependent inhibition of thrombosis in venous and arteriovenous thrombosis models. However, due to the more aggressive nature of thrombotic stimulation in the arteriovenous shunt model, complete cessation of thrombus growth was not achieved for any of the agents at the doses tested. Comparison between the agents focused on the differences in extension of coagulation parameters (activated partial thromboplastin time, prothrombin time, thrombin clotting time), changes in hematological parameters, and extension of rabbit cuticle bleeding time at doses required to produce maximum inhibition in the thrombosis models. In the venous thrombosis model at the maximally effective dose, C921-78 had minimal extension of ex vivo clotting parameters, while enoxaparin and unfractionated heparin demonstrated a two to sevenfold increase in activated partial thromboplastin times, and PPACK had a threefold extension of thrombin clotting times. In addition, unlike the other three agents, which exhibited no significant changes in hematological parameters, PPACK demonstrated dose dependent thrombocytopenia. A standardized cuticle bleeding time was used as a measure of perturbation of hemostasis. The agents were evaluated for significant increases in bleeding time at doses up to eight times that needed to completely inhibit venous thrombus formation. Unfractionated heparin displayed a significant bleeding time effect at the dose required to inhibit venous thrombosis (100 u/kg+2 u/kg/min). Enoxaparin and PPACK caused significant bleeding time extensions at four times the fully efficacious venous dose (800 u/kg+8 u/kg/min and 30 microg/kg/min). By contrast, C921-78 did not significantly increase bleeding time even at eight times the maximally effective dose (240 microg/kg+7.2 microg/kg/min). Our results demonstrate that specific inhibition of fXa can be utilized to derive potent antithrombotic activity without disrupting extravascular hemostasis.

Amino Acid Chloromethyl Ketones↗
PubMed2000

Autosomal dominant Stargardt-like macular dystrophy segregating in a large Canadian family.

BACKGROUND: Inherited macular dystrophies account for a major fraction of the cases of retinal degenerative disease that lead to permanent blindness. We describe the clinical and genetic findings in a Canadian family with a form of macular dystrophy resembling autosomal dominant Stargardt-like macular dystrophy. METHODS: Standard ophthalmologic examinations were performed in members of a single five-generation Alberta family. Tests of visual acuity and colour vision, fundus photography, fluorescein angiography and electroretinography were performed in 15 affected people. Blood was collected from 24 family members, and DNA was extracted for genotyping. Genetic linkage analysis was performed using polymorphic short tandem repeat microsatellite markers located on chromosome 6q, a region containing loci for several macular disorders. RESULTS: Affected family members display clinical characteristics resembling autosomal dominant Stargardt-like macular dystrophy, previously assigned to chromosome 6q (STGD3). Linkage analysis generated a peak lod score of 5.50 at an estimated recombination fraction of 0.00 for marker locus D6S300. INTERPRETATION: The family described has an autosomal dominant macular dystrophy that resembles Stargardt-like macular dystrophy. The disease locus for this family maps to an interval on chromosome 6q that overlaps that for STGD3 and other retinal dystrophy loci. These findings provide further evidence that human chromosome 6q represents a "hot spot" for retinal disorders.

Adolescent↗
PubMed2000

The effect of varying inspiratory flow waveforms on pulmonary mechanics in critically ill patients.

PURPOSE: Ten mechanically ventilated patients were evaluated to determine the effect of three different inspiratory flow patterns on pulmonary mechanics. MATERIALS AND METHODS: Ten consecutive mechanically ventilated critically ill patients with acute respiratory failure admitted to the intensive care unit were evaluated to assess the effects of decelerating, square, and sine waveforms on pulmonary mechanics. The variables measured were peak airway pressure (PaW), pleural pressure (Ppl), change in peak airway pressure (dPaW), inspiration time/total ventilation cycle time (Vi/tot), dynamic compliance (Cdyn), respiratory rate (RR), minute ventilation (Ve), and work of breathing (WOB). RESULTS: The PaW, Ppl, and dPaW (cm H2O) were significantly lower using the decelerating inspiratory flow waveform (P<.05) compared with sine or square waveform patterns. Ti/Ttot was also lower with the decelerating waveform (P<.05) with better dynamic compliance compared with the other waveforms (P<.10). CONCLUSIONS: These results indicate that critically ill mechanically ventilated patients show improved respiratory mechanics with decelerating inspiratory waveform that may have beneficial clinical implication.

Adult↗
PubMed2000

The utility of open lung biopsy in patients with hematologic malignancies.

The yield and impact of open lung biopsies in patients with hematologic malignancies and unexplained pulmonary processes were assessed and analyzed to determine factors that affected the yield. Records of 63 patients with hematologic malignancy, who underwent 67 open lung biopsies for diagnosis of an unknown pulmonary process from 1996 to 1998 at Memorial Sloan-Kettering Cancer Center, were retrospectively reviewed. A specific diagnosis was found in 41 (62%) of the biopsies. Changes in therapy were made in 37 (57%) of patients after biopsy results, but in 69% of those with a specific diagnosis. Survival at 30 and 90 d was increased in those with specific rather than a nonspecific pulmonary diagnosis. The factor most predictive of finding a specific diagnosis was the presence of a focal rather than a diffuse radiographic abnormality (79% versus 36%, p = 0.003). Neutropenic patients or those on mechanical ventilation had a low chance of finding a specific diagnosis. Having received pulmonary toxic chemotherapy in the 6 mo before the biopsy was associated with finding a nonspecific lung injury. Specific pulmonary diagnoses found were inflammatory diseases in 23% of cases, infections in 21%, and malignancy in 18%. Bronchiolitis obliterans with organizing pneumonia (BOOP) was the most common inflammatory disorder and fungi and bacteria were the most frequent infectious pathogens. Complications occurred in 13% of the biopsies, including five patients who required mechanical ventilation post-procedure; one death was associated with the biopsy. The risk was increased in those with less than 50,000 platelets. Complications were similar with video-assisted thoracoscopy (VATS) compared with thoracotomy. We conclude that open lung biopsy in patients with hematologic malignancy has a significant yield and impact on management of patients with hematologic malignancy.

Adolescent↗
PubMed1999

Inhibition of factor Xa by a peptidyl-alpha-ketothiazole involves two steps. Evidence for a stabilizing conformational change.

Recently, peptidylketothiazoles have been shown to be potent inhibitors of proteases, but the details of the interaction have not yet been studied. In the work presented here, the interaction of factor Xa, a coagulation protease, with the transition state inhibitor BnSO(2)-D-Arg-Gly-Arg-ketothiazole (C921-78) is characterized. C921-78 is a tight and selective inhibitor of the coagulation protease factor Xa (K(d) = 14 pM). The hydrolytic activity of factor Xa was inhibited by C921-78 in a time-dependent manner. The rate-limiting step of the bimolecular combination of inhibitor and enzyme was competitive with the substrate. Conversely, the inhibitor could be displaced from the active site of the enzyme after exposure of the preformed complex to an excess of substrate or to the active site inhibitor dansyl-Glu-Gly-Arg-chloromethyl ketone (DEGR-CMK) in a slow reaction. The formation of the C921-78-factor Xa complex resulted in a 60% increase in the magnitude of the fluorescence emission spectrum. Rapid mixing of the enzyme and inhibitor produces a monophasic fluorescence increase, compatible with spectral transition in a single step. The rate constant for this reaction increased hyperbolically with the concentration of C921-78, but the amplitude remained constant. These results are consistent with the initial formation of an enzyme-inhibitor complex (EI), followed by a unimolecular conversion of EI to EI linked to a spectral transition. The rate constants of the isomerization provide an estimate of 300000-fold stabilization. Thus, the inhibition of factor Xa by C921-78 follows a mechanism similar to that described classically for slow tight binding inhibitors. However, the two steps of the reaction cannot be kinetically separated by the rapid equilibrium assumption, and therefore, the formation of EI is partially rate-limiting, too. The driving energy for the unusually fast isomerization step may result from the highly favorable interactions of the inhibitor in the primary binding site.

Amino Acid Sequence↗
PubMed1999

Acute effect of nicotine patch on gastric emptying of liquid and solid contents in healthy subjects.

The effect of nicotine on gastric emptying remains controversial. Gastric emptying is delayed in chronic smokers after smoking high-dose nicotine cigarettes, but it is unchanged after chewing nicotine gums. No information is available on the effect of transdermal nicotine patches on the gastric emptying of solid and liquid contents in healthy nonsmokers. Our objective was to prospectively evaluate the effect of the nicotine patch on gastric emptying of liquid and solid contents in healthy nonsmokers. Ten healthy nonsmoking volunteers underwent a baseline dual-isotope gastric scintigraphy with [111In]-diethylenetriaminepantaacetic acid (DTPA) and [99mTc]sulfur colloid isotopes to evaluate prospectively the gastric emptying of liquid and solid contents, respectively. The gastric scintigraphy was repeated after placing a transdermal nicotine patch (Habitrol) for 12 hr designed to deliver 14 mg of nicotine per day. Plasma nicotine level was measured prior to baseline gastric scintigraphy and after 12 hr placing the nicotine patch. Plasma nicotine was absent in all subjects at baseline and but was significantly elevated after 12 hr of nicotine patch (P < 0.009). The mean half-emptying times (T1/2) for the gastric emptying of liquids before and after nicotine patch placement were 31.2+/-23.3 and 25.6+/-8.4 min, respectively (P = 0.498). The mean T1/2s for the gastric emptying of solids before and after nicotine patch placement were 70.1+/-34.0 and 59.7+/-31.4 min, respectively (P = 0.202). There was no correlation between the plasma nicotine level and gastric emptying of liquid and solid contents (correlation coefficient = -0.23 and -0.01, respectively). In conclusion, acute transdermal delivery of nicotine does not affect the gastric emptying of solid and liquid contents in healthy nonsmoking subjects.

Administration, Cutaneous↗
PubMed1999

How to deal with chronic constipation. A stepwise method of establishing and treating the source of the problem.

Chronic constipation is a common medical complaint encountered often in a primary care setting. Most patients can be treated successfully with simple measures, including education, bowel habit training, increased fluid and fiber intake, and use of laxatives. Chronic constipation is usually considered idiopathic, but secondary causes should be excluded. In about 1% of patients with severe, intractable constipation, further diagnostic testing (e.g., endoscopy, colonic transit study) is needed. Patients with colonic inertia can be treated with judicious use of laxatives, but surgery may be necessary in a few cases. Patients with outlet inertia should be referred for biofeedback treatment.

Anus Diseases↗
PubMed1998

An enzyme-linked immunosorbent assay for the detection of agents which interfere with the DNA binding activities of transcription factors--exemplified by NF-IL6.

Binding of transcription factors to DNA is usually detected by the electrophoretic mobility shift assay also known as gel-shift or band-shift assay. Recently the use of biosensors has allowed factor/DNA interactions to be followed in real time. However, neither of these approaches lends itself easily to high-throughput screening of agents which might interfere with this process. We have therefore developed a 96-well plate-based enzyme-linked immunosorbent assay for this purpose. Biotinylated oligonucleotides bound to streptavidin-coated plates are used to capture recombinant transcription factor proteins which can then be detected using specific antibodies which in turn are recognised by peroxidase-conjugated antisera. The peroxidase catalyzes conversion of a colorless substrate to a colored product which can be quantified by optical densitometry on a plate reader. Agents which interfere with the binding of the transcription factor to DNA reduce the optical density in the well. Using the NF-IL6 transcription factor we show that the assay can detect reductions to 86% at significant levels. The assay may be readily adapted for robotic manipulation, making it ideal for high-throughput screening.

Base Sequence↗
PubMed1998

The value of screening for psychiatric disorders prior to upper endoscopy.

Gastrointestinal (GI) complaints are among the most common symptoms in primary care yet are frequently unexplained and often lead to costly diagnostic testing. We sought to determine the prevalence of psychiatric disorders in patients with unexplained GI complaints undergoing upper endoscopy, and the likelihood of endoscopic abnormalities in patients with and without psychiatric diagnoses. We prospectively evaluated 116 adult patients who were undergoing upper endoscopy to evaluate GI complaints. All subjects received a structured psychiatric interview prior to endoscopy using PRIME-MD, and endoscopists were blinded to the PRIME-MD results. Psychiatric disorders were detected in 70 (60%) patients. Overall, there were 113 diagnoses (some patients had multiple disorders) with the most common being somatoform (44%), depressive (29%), and anxiety (19%) disorders. Only 29 patients had major endoscopic abnormalities, including esophageal disease (14), peptic ulcer (9), severe gastritis (4), gastric cancer (1), and esophageal cancer (1). There was a much higher prevalence of psychiatric disorders in patients without major endoscopic abnormalities (74% vs. 21%, p < 0.0001). Psychiatric disease was strongly predictive of endoscopic findings (OR for major abnormality = 0.11 in women, and 0.40 in men), especially if somatoform disorder was present (OR = 0.15). We conclude that, with a simple questionnaire, psychiatric disorders can be diagnosed in a large proportion of patients with unexplained GI complaints who are referred for upper endoscopy. The presence of a psychiatric disorder, particularly if somatoform, makes it unlikely that endoscopy will reveal significant GI disease.

Adult↗
PubMed1998

Stridor as a manifestation of supraglottic carcinoma in a patient with AIDS.

As patients with human immunodeficiency virus (HIV) infection are living longer, the differential diagnosis of stridor in acquired immunodeficiency syndrome (AIDS) patients should be broadened to include malignancies in addition to the common causes of infections and functional airway abnormalities. Herein, we describe a 50-year-old woman with AIDS who presented with stridor secondary to supraglottic squamous cell carcinoma.

Carcinoma, Squamous Cell↗
PubMed1998

Multiple organ toxicity from addition of erythromycin to long-term lovastatin therapy.

A patient who had taken lovastatin for 7 years received erythromycin before dental procedures. Multiple organ toxicity developed, manifested as rhabdomyolysis, acute renal failure, pancreatitis, ileus, livedo reticularis, and elevated aminotransferase values, without liver injury. No previous reports have identified multiple organ injury of this magnitude. A computer literature search identified only three other reported instances of erythromycin and lovastatin interaction. Manifestations in these previous cases consisted of rhabdomyolysis in all three, as well as elevated aminotransferase values and acute renal failure in two cases. In all the cases, the clinical presentation of organ toxicity occurred after the cessation of erythromycin therapy between day 1 and day 5. Advanced age and chronic renal insufficiency were identified as potential risk factors for drug interaction. Health care professionals should be aware of the potential interaction between these two commonly prescribed drugs, which can mimic sepsis.

Acute Kidney Injury↗