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David T Wong

Publications and source records attributed to David T Wong.

At least 37 records · Page 2Linked to original sources
PubMed2005

Advances toward new antidepressants beyond SSRIs: 1-aryloxy-3-piperidinylpropan-2-ols with dual 5-HT1A receptor antagonism/SSRI activities. Part 5.

A series of 1-aryloxy-3-piperidinylpropan-2-ols possessing potent dual 5-HT1A receptor antagonism and serotonin reuptake inhibition was discovered. 1-(1H-Indol-4-yloxy)-3-(4-benzo[b]thiophen-2-ylpiperidinyl)propan-2-ols exhibited selective and high affinities at the 5-HT1A receptor and serotonin reuptake site in vitro. In vivo evaluation of this series of compounds demonstrated elevated extracellular serotonin levels from the basal and quick recovery of neuron firing that was presumably suppressed by the initial acute activation of 5-HT1A somatodendritic autoreceptors.

Animals↗
PubMed2005

Anterior cervical screw extrusion leading to acute upper airway obstruction: case report.

STUDY DESIGN: Case report of late postoperative complication. SUMMARY OF BACKGROUND DATA: There have been a number of reports of migration and extrusion of cervical fusion instrumentation. The majority of such cases have a benign outcome. To our knowledge, cervical instrumentation extrusion resulting in prevertebral abscess and acute airway obstruction has not been reported. METHODS: A 56-year-old man who had undergone a prior C3-C6 anterior cervical decompression and fusion presented to a hospital with dysphagia and acute airway obstruction requiring an emergency tracheostomy. His neck radiograph showed that a C6 screw was missing compared to prior films. Magnetic resonance imaging showed a large prevertebral abscess anterior to C2-C7 causing complete upper airway obstruction. RESULTS: He underwent surgical drainage of the abscess and had a good neurologic recovery. CONCLUSIONS: We report a case of acute upper airway obstruction from prevertebral abscess, likely secondary to a loosened anterior cervical screw penetrating the prevertebral soft tissue. In contrast to case reports in the literature involving instrumentation extrusion with a usually benign outcome, our case presented with a life-threatening condition.

Airway Obstruction↗
PubMed2005

Mutation of Cys105 inhibits dimerization of p12CDK2-AP1 and its growth suppressor effect.

p12(CDK2-AP1) (p12) is a CDK2-associated protein that negatively regulates its kinase activity. Growth arrest of normal diploid cells by contact inhibition resulted in an induction of p27(kip1) and reduction of CDK2 levels. Interestingly, we observed concomitantly in growth-arrested cells, there was a reduction of nuclear p12 and the appearance of a nuclear 25-kDa molecule (p25) recognized by anti-p12 polyclonal antibody. Biochemical analysis showed that bacterial His-tagged p12 could be converted into a dimeric p25 in a reducing agent-dependent manner, and mutating the only cysteine residue of p12 (Cys(105) --> Ala(105)) abolished the dimerization. Transient transfection of wild type p12 into U2OS cells showed a reducing agent-sensitive dimerization that was also abolished by the C105A mutation. Furthermore, reduction of p12 expression by a short interfering RNA resulted in a parallel reduction of p25. These data supports the possibility that p25 is a homodimeric form of p12 through the cysteine residue. More interestingly, transient transfection of p12 (C105A) into the normal diploid lung fibroblast CCD18LU cells resulted in a reduction of the growth-inhibitory effect of p12 and abolished the inhibitory effect of p12 on CDK2 kinase activity. In addition, we found that the C105A mutation did not alter nuclear localization of p12, but it prevented association with CDK2. Taken together, our data suggest that p12 forms a nuclear homodimers in contact inhibited normal diploid cells and dimerization of p12 is a necessary process for the growth inhibition effect by p12.

Alanine↗
PubMed2005

p12(CDK2-AP1) mediates DNA damage responses induced by cisplatin.

We examined the biological role of p12(CDK2-AP1) in cisplatin-mediated responses by using murine ES p12(CDK2-AP1) knockout clones generated by a targeted disruption of murine p12(CDK2-AP1). Homozygous knockout clones showed an increased cellular proliferation along with an increase in S and a decrease in G2/M phase populations. Interestingly, ES p12(CDK2-AP1) knockout clones showed a resistance to cisplatin treatment along with an increased DNA repair activity assessed by host cell reactivation assay using a cisplatin-damaged reporter DNA and a significant reduction of apoptosis upon cisplatin treatment. By using stable p12(CDK2-AP1) short interfering RNA (siRNA) clones from human normal oral keratinocytes, we confirmed that downregulation of p12(CDK2-AP1) resulted in a resistance to cisplatin. More interestingly, cisplatin treatment resulted in a reduction of CDK2 kinase activity in control clones, but p12(CDK2-AP1) knockout clones showed a sustained CDK2 kinase activity. These data suggest that p12(CDK2-AP1) plays a role in cisplatin-mediated cellular responses by modulating CDK2 activity. These data further suggest p12(CDK2-AP1) is a potential gene therapeutic agent for oral/head and neck cancer in conjunction with DNA-damaging agents such as cisplatin.

Animals↗
PubMed2005

Large-scale identification of proteins in human salivary proteome by liquid chromatography/mass spectrometry and two-dimensional gel electrophoresis-mass spectrometry.

Human saliva contains a large number of proteins and peptides (salivary proteome) that help maintain homeostasis in the oral cavity. Global analysis of human salivary proteome is important for understanding oral health and disease pathogenesis. In this study, large-scale identification of salivary proteins was demonstrated by using shotgun proteomics and two-dimensinal gel electrophoresis-mass spectrometry (2-DE-MS). For the shotgun approach, whole saliva proteins were prefractionated according to molecular weight. The smallest fraction, presumably containing salivary peptides, was directly separated by capillary liquid chromatography (LC). However, the large protein fractions were digested into peptides for subsequent LC separation. Separated peptides were analyzed by on-line electrospray tandem mass spectrometry (MS/MS) using a quadrupole-time of flight mass spectrometer, and the obtained spectra were automatically processed to search human protein sequence database for protein identification. Additionally, 2-DE was used to map out the proteins in whole saliva. Protein spots 105 in number were excised and in-gel digested; and the resulting peptide fragments were measured by matrix-assisted laser desorption/ionization-mass spectrometry and sequenced by LC-MS/MS for protein identification. In total, we cataloged 309 proteins from human whole saliva by using these two proteomic approaches.

Chromatography, Liquid↗
PubMed2005

Modified Mallampati test, thyromental distance and inter-incisor gap are the best predictors of difficult laryngoscopy in West Africans.

PURPOSE: To determine the ability to predict difficult visualization of the larynx (DVL) from the following preoperative airway predictive indices, in isolation and combination: modified Mallampati test (MMT), thyromental distance (TMD), sternomental distance (SMD), horizontal length of the mandible (HLM) and inter-incisor gap (IIG). METHODS: Three hundred and eighty consecutive patients undergoing general anesthesia were evaluated using the MMT, TMD, SMD, HLM and IIG and the cut-off points for the airway predictors were Mallampati III and IV; < or = 6.5 cm, < or = 13.5 cm, < or = 9.0 cm and < or = 4.0 cm respectively. During direct laryngoscopy, the laryngeal view was graded using the Cormack and Lehane (CL) classification. CL grades III and IV were considered difficult visualization. Sensitivity, specificity and positive predictive value for each airway predictor in isolation and in combination were determined. Logistic regression analysis was used to determine independent predictors of DVL. RESULTS: Difficulty to visualize the larynx was found in 13 (3.4%) patients. The sensitivity, specificity and the positive predictive value for the five airway predictors were: MMT (61.5%; 98.4%; 57.1%), TMD (15.4%; 98.1%; 22.2%), SMD (0%; 100%; 0%), HLM (30.8%, 76.0%; 4.3%) and IIG (30.8%; 97.3%; 28.6%). The best combination of predictors was MMT/TMD/IIG with a sensitivity, specificity and positive predictive value of 84.6%; 94.6%; 35.5% respectively. Logistic regression analysis showed that weight, MMT, IIG and TMD were independent predictors of DVL. CONCLUSION: MMT, TMD and IIG appear to provide the optimal combination in prediction of DVL in a West African population.

Adult↗
PubMed2005

Unilateral subcutaneous emphysema after percutaneous tracheostomy.

PURPOSE: Percutaneous tracheostomy techniques are widely used in intensive care units. Subcutaneous emphysema is a rare but well recognized complication associated with this procedure. We report an unusual presentation of sc emphysema after percutaneous tracheostomy. The clinical features, diagnosis and postulated mechanism are discussed. CLINICAL FEATURES: A 39-yr-old man had percutaneous tracheostomy done after prolonged intubation in the intensive care unit. Subcutaneous emphysema developed over the right neck fever mimicking deep sc infection resulted in neck exploration. No obvious lesion was found in the tracheobronchial tree. CONCLUSION: Subcutaneous emphysema occurring after percutaneous tracheostomy could occur without significant injury to the tracheobronchial tree. We postulate that air leaking from the tracheostomy site might have been prevented by the snug fit between the tracheostomy tube and the skin, resulting in accumulation in the neck. Asymmetric dilatation of the trachea may explain the unilateral localization of the sc emphysema.

Adult↗
PubMed2005

Progress in concurrent analysis of loss of heterozygosity and comparative genomic hybridization utilizing high density single nucleotide polymorphism arrays.

Genetic aberrations, such as deletions and amplifications are among the major pathogenetic mechanisms underlying many medical disorders. Analysis of chromosomal aberrations is particularly important in cancer research, where amplifications of oncogenes and deletions of tumor suppressor genes are major steps in the "multi-hit" process of tumorigenesis. Genome-wide molecular biological analyses, such as loss of heterozygosity (LOH) profiling and comparative genomic hybridization (CGH) have significantly enhanced our ability to detect chromosomal aberrations in cancer cells and assess their role in tumorigenesis. The recent introduction of high-density oligonucleotide arrays for measuring single nucleotide polymorphisms (SNP) has sparked a new wave of high-resolution genetic mapping studies, including LOH and CGH applications on various cancer types. This review highlights recent progress on concurrent LOH and CGH analyses utilizing high density SNP arrays and their application in cancer research.

Genome, Human↗
PubMed2005

In situ and non-invasive detection of specific bacterial species in oral biofilms using fluorescently labeled monoclonal antibodies.

Noninvasive in situ detection of suspected cariogenic bacterial species within dental biofilms could facilitate monitoring of the dynamic change of oral microbial flora and assist in the assessment of the treatment efficacy of therapeutic agents. In this study, we explore the possibility to use three well-characterized monoclonal antibodies (MAbs) against Streptococcus mutans, Actinomyces naeslundii, and Lactobacillus casei to identify these three important members of the oral microbial community in the complex environment of oral biofilms. These MAbs, which were conjugated to different fluorescent labels and visualized with confocal laser scanning microscopy (CLSM), proved to be an useful tool to identify the three species of interest (S. mutans, A. naeslundii, and L. casei) under various experimental conditions including in vitro and in vivo derived oral biofilms. Manifold addition of the MAbs on consecutive days did not alter the biofilm structure thus allowing monitoring of the same biofilm over extended time periods. Using this MAb-based method the effect of sucrose challenge on the biofilm composition and the distribution of S. mutans, A. naeslundii, and L. casei were examined. S. mutans was found to be the predominant species under the various biofilm conditions tested. These studies indicate that MAbs based bacterial detection with CLSM is a versatile tool which permits new insights into the ecology of oral biofilm development.

Actinomyces↗
PubMed2005

Surgical repositioning of dislocated capsular tension rings.

PURPOSE: To present techniques and results of surgical repositioning of subluxed and dislocated capsular tension rings (CTRs). DESIGN: Retrospective interventional case series. PARTICIPANTS: Eleven patients with a previously implanted CTR in-the-bag for zonular weakness who presented with CTR-intraocular lens (IOL)-capsular bag decentration who underwent surgical repositioning. METHODS: Data from 11 patients who underwent surgical repositioning were evaluated retrospectively for underlying diagnosis, interval between initial surgery and decentration, surgical technique, clinical results, and complications. MAIN OUTCOME MEASURES: Capsular tension ring-IOL-capsular bag centration, final best-corrected visual acuity (BCVA), and surgical complications. RESULTS: Of the 11 patients with CTR decentration, 3 had it early in the postoperative period, and 8 had it late. Mean (+/- standard deviation) durations from cataract extraction and CTR implantation to surgical repositioning were 6.1+/-7.9 months for those with decentration early and 49.6+/-15.3 months for late decentrations (overall range, 0.7-74.7). Of the 11 patients, 7 had pseudoexfoliation, and 4 of the 7 had associated glaucoma. Nine patients had subluxation of the CTR-IOL-capsular bag complex, which was managed by an anterior segment approach. A pars plana vitrectomy and levitation of the CTR was required in 2 patients due to complete dislocation of the CTR into the posterior vitreous. Surgical techniques for repositioning included single, double, or 3-point scleral suture loop fixation of the CTR through the capsular bag complex (8 eyes); use of the capsular tension segment (CTS) placed within the capsular bag for scleral suture fixation (2); or iris suture fixation of the IOL haptics (1). All patients achieved successful anatomical repositioning of the CTR-IOL-capsular bag complex. Mean preoperative BCVA improved from 20/100 to 20/40 postoperatively. After repositioning surgery, BCVA improved in 7 patients, was maintained in 2, and worsened in 2 (due to advanced glaucoma). CONCLUSION: Postoperative CTR subluxation or dislocation is a risk for patients with severe or progressive zonulopathy. Decentrations may be effectively managed with scleral suture fixation of the CTR through the capsular bag or the use of the CTS.

Aged↗
PubMed2005

Case history: the discovery of fluoxetine hydrochloride (Prozac).

In the early 1970s, evidence of the role of serotonin (5-hydroxytryptamine or 5-HT) in depression began to emerge and the hypothesis that enhancing 5-HT neurotransmission would be a viable mechanism to mediate antidepressant response was put forward. On the basis of this hypothesis, efforts to develop agents that inhibit the uptake of 5-HT from the synaptic cleft were initiated. These studies led to the discovery and development of the selective serotonin-reuptake inhibitor fluoxetine hydrochloride (Prozac; Eli Lilly), which was approved for the treatment of depression by the US FDA in 1987. Here, we summarize this research and discuss the many challenges that we encountered during the development of fluoxetine hydrochloride, which has now been widely acknowledged as a breakthrough drug for depression.

Depression↗
PubMed2005

Late-onset macular degeneration and long anterior lens zonules result from a CTRP5 gene mutation.

PURPOSE: To identify the gene responsible for a complex ocular phenotype of late-onset macular degeneration, long anterior zonules (LAZ), and elevated intraocular pressure (IOP) and to study its expression. METHODS: Ocular examination, visual field, fluorescein angiography, and electrophysiology testing were performed. One affected individual was treated with vitamin A. DNA from 55 family members (UM:H389) was used for linkage, mapping, and mutation analysis. Linkage analysis of macular degeneration and LAZ phenotypes was performed independently. Mutations in candidate genes were screened by sequencing. mRNA expression of CTRP5 and MFRP, which are bicistronic genes, was studied by semiquantitative RT-PCR (qRT-PCR) in various human tissues. CTRP5 expression was also evaluated by in situ hybridization. RESULTS: Affected members had LAZ detectable by the third decade and/or macular degeneration by the fourth to fifth decade. A six-month treatment with vitamin A shortened dark adaptation considerably in one affected member. Both conditions mapped independently with zero recombination to 11q23, with maximum lod scores of 3.31 for macular degeneration and 5.41 for LAZ. The same CTRP5 missense mutation was identified in all affected individuals. Retinal pigment epithelium (RPE) and ciliary epithelium (CE) showed highest CTRP5 transcript expression, which was also true for MFRP. CTRP5 tissue expression was confirmed by in situ hybridization. CONCLUSIONS: A single locus at 11q23 is implicated in a complex ocular phenotype involving RPE and CE, tissues of neuroectodermal origin. All individuals with either LAZ and/or macular degeneration carry the same CTRP5 S163R mutation, which is transmitted in autosomal dominant manner.

Adult↗
PubMed2005

Cannot intubate-cannot ventilate and difficult intubation strategies: results of a Canadian national survey.

The purpose of this study was to determine the preferences of Canadian anesthesiologists in difficult intubation and cannot intubate-cannot ventilate (CICV) situations. Using a mailed survey, we asked anesthesiologists their preferences for and comfort level in using (a) alternative airway devices in a difficult intubation scenario and (b) infraglottic airway in a CICV scenario. Chi-square analysis and Student's t-test were used for categorical and continuous variables. Nine-hundred-seventy-one of 2066 surveys were returned. In the difficult intubation scenario, the preferred alternative airway devices were lighted stylet (45%), fiberoptic bronchoscope (26%), and intubating laryngeal mask airway (20%). Only 57% of respondents had encountered a CICV situation in real life. In the CICV scenario, preferred infraglottic airways were cricothyroidotomy by IV catheter (51%), percutaneous cricothyroidotomy (28%), and tracheostomy by surgeon (14%). Anesthesiologists had little experience and were uncomfortable with open surgical infraglottic airways. Anesthesiologists with experience using infraglottic airways on mannequins were more comfortable using them in patients (P < 0.001). In conclusion, in a difficult intubation scenario, the lighted stylet has emerged as the preferred alternative airway device. In a CICV scenario, respondents preferred cricothyroidotomy by IV catheter, followed by percutaneous cricothyroidotomy and tracheostomy by surgeon. Practice on mannequins was associated with improved comfort in using infraglottic airways in patients.

Adult↗
PubMed2004

Cyclin G2 dysregulation in human oral cancer.

Using expression microarray, we have previously shown that human cyclin G2 (hCG2) is significantly down-regulated in laser capture microdissected oral cancer epithelia. Western analysis showed detectable hCG2 protein in normal (2 of 2) but not in malignant (4 of 4) oral keratinocyte cell lines. Immunohistochemistry analysis done on oral cancers showed that normal oral mucosa (100%, 12 of 12) and 69.1% (47 of 68) of dysplastic oral epithelia expressed readily detectable hCG2 in the nuclei. However, only 11.1% of oral cancer epithelia (14 of 126) showed mild hCG2 nuclear staining. Interestingly, of the oral cancers devoid of nuclear hCG2 (112 cases), 58 cases (52%) showed cytoplasmic hCG2 immunostaining, whereas the other 54 cases (48%) exhibited neither nuclear nor cytoplasmic hCG2 staining. In vitro functional study by ectopic restoration of hCG2 expression in the human malignant squamous cell carcinoma (SCC) line SCC15 resulted in a significant inhibition of cellular proliferation (P < 0.001) and colony formation (P < 2 x 10(-5)) with increased population of G(1) phase and decreased in S phase (P < 0.01). Furthermore, stable down-regulation of hCG2 by short interference RNA-based gene silencing in immortalized normal oral keratinocytes resulted in enhanced cell growth with increase in S and prominently in G(2) phase. Because hCG2 has been implicated as a negative regulator in cell cycle progression, our results support that hCG2 dysregulation may play an important role in epithelial transformation and the early stages of human oral cancer development.

Animals↗
PubMed2004

Salivary transcriptome diagnostics for oral cancer detection.

PURPOSE: Oral fluid (saliva) meets the demand for noninvasive, accessible, and highly efficient diagnostic medium. Recent discovery that a large panel of human RNA can be reliably detected in saliva gives rise to a novel clinical approach, salivary transcriptome diagnostics. The purpose of this study is to evaluate the diagnostic value of this new approach by using oral squamous cell carcinoma (OSCC) as the proof-of-principle disease. EXPERIMENTAL DESIGN: Unstimulated saliva was collected from patients (n = 32) with primary T1/T2 OSCC and normal subjects (n = 32) with matched age, gender, and smoking history. RNA isolation was done from the saliva supernatant, followed by two-round linear amplification with T7 RNA polymerase. Human Genome U133A microarrays were applied for profiling human salivary transcriptome. The different gene expression patterns were analyzed by combining a t test comparison and a fold-change analysis on 10 matched cancer patients and controls. Quantitative polymerase chain reaction (qPCR) was used to validate the selected genes that showed significant difference (P < 0.01) by microarray. The predictive power of these salivary mRNA biomarkers was analyzed by receiver operating characteristic curve and classification models. RESULTS: Microarray analysis showed there are 1,679 genes exhibited significantly different expression level in saliva between cancer patients and controls (P < 0.05). Seven cancer-related mRNA biomarkers that exhibited at least a 3.5-fold elevation in OSCC saliva (P < 0.01) were consistently validated by qPCR on saliva samples from OSCC patients (n = 32) and controls (n = 32). These potential salivary RNA biomarkers are transcripts of IL8, IL1B, DUSP1, HA3, OAZ1, S100P, and SAT. The combinations of these biomarkers yielded sensitivity (91%) and specificity (91%) in distinguishing OSCC from the controls. CONCLUSIONS: The utility of salivary transcriptome diagnostics is successfully demonstrated in this study for oral cancer detection. This novel clinical approach could be exploited to a robust, high-throughput, and reproducible tool for early cancer detection. Salivary transcriptome profiling can be applied to evaluate its usefulness for other major disease applications as well as for normal health surveillance.

Biomarkers, Tumor↗
PubMed2004

Advances toward new antidepressants beyond SSRIs: 1-aryloxy-3-piperidinylpropan-2-ols with dual 5-HT1A receptor antagonism/SSRI activities. Part 4.

A series of 1-(1H-indol-4-yloxy)-3-(4-arylpiperidinyl)propan-2-ols possessing potent dual 5-HT(1A) receptor antagonism and serotonin reuptake inhibition was discovered. The fused aryl ring moiety contributed to the robust dual activities irrespective of the regiochemistry associated with its connectivity to the piperidine central ring.

Antidepressive Agents, Second-Generation↗
PubMed2004

Ambulatory surgery adult patient selection criteria - a survey of Canadian anesthesiologists.

PURPOSE: An increasing number of patients with complex medical problems are now considered suitable for ambulatory surgery. The purpose of this study was to identify the current clinical practice of ambulatory surgical patient selection. METHODS: A standardized questionnaire specifying 30 clinical conditions was sent to all practicing anesthesiologists who are members of the Canadian Anesthesiologists' Society. Recipients were asked to indicate if they would provide ambulatory anesthesia (yes/no answers) for an adult patient with each of those isolated conditions. A 75% agreement was considered a majority opinion. RESULTS: One thousand three hundred thirty-seven questionnaires were sent and 774 replies were received (57.8%). Over 75% of anesthesiologists were willing to include in their selection criteria American Society of Anesthesiologists' (ASA) physical status III, patients with low-grade angina pectoris (AP) and congestive heart failure (CHF), prior myocardial infarction, asymptomatic valvular disease, sleep apnea without use of narcotics, morbid obesity (MO) without co-morbidities, insulin dependent diabetes mellitus and malignant hyperthermia (MH) susceptible patients. Over 75% of responders found ASA IV patients, high grade AP and CHF, sleep apnea with postoperative narcotics, MO with co-morbidities and no patient escort to be unsuitable for ambulatory anesthesia. CONCLUSION: Our survey demonstrated that medical conditions with extreme grades of severity (mild or severe) are associated with majority opinion to proceed or not to proceed with ambulatory surgery. Issues with over 75% agreement reflect the common practice. Similar surveys may form a part of patient selection guidelines development in the future.

Adult↗