Biomedical subjects

D T Wong

Publications and source records attributed to D T Wong.

At least 55 records · Page 3Linked to original sources

PubMed1999

Direct measures of large, anisotropic strains in deformation of the erythrocyte cytoskeleton.

The erythrocyte's spectrin-actin membrane skeleton is directly shown to be capable of sustaining large, anisotropic strains. Photobleaching of an approximately 1-micrometer stripe in rhodamine phalloidin-labeled actin appears stable up to at least 37 degrees C, and is used to demonstrate large in-surface stretching during elastic deformation of the skeleton. Principal extension or stretch ratios of at least approximately 200% and contractions down to approximately 40%, both referenced to an essentially undistorted cell, are visually demonstrated in micropipette-imposed deformation. Such anisotropic straining is seen to be consistent at a qualitative level with now classic analyses (Evans. 1973. Biophys. J. 13:941-954) and is generally nonhomogeneous though axisymmetric down to the submicron scale. Local, direct measurements of stretching prove quantitatively consistent (within approximately 10%) with integrated estimates that are based simply on a measured relative density distribution of actin. The measurements are also in close agreement with direct computation of mean spectrin chain extension in full statistical mechanical simulations of a coarse-grained network held in a micropipette. Finally, as a cell thermally fragments near approximately 48 degrees C, the patterned photobleaching demonstrates a destructuring of the surface network in a process that is more readily attributable to transitions in spectrin than in F-actin.

Actins↗

PubMed1999

Eosinophil-derived transforming growth factors (TGF-alpha and TGF-beta 1) in human periradicular lesions.

Inflammatory mediators of periradicular lesions are poorly understood. Transforming growth factors-alpha and -beta 1 (TGF-alpha and TGF-beta 1) have been linked with the cellular processes for both soft and hard tissue wound healing. The purpose of this study is to demonstrate the cellular sources of TGF-alpha and TGF-beta 1 mRNA and protein in periapical lesions by in situ hybridization and immunohistochemistry. Nine periapical granulomas and nine periapical cysts were examined. TGF-alpha mRNA and protein were not detectable in the granulomas examined. However, eosinophils surrounding the periapical cysts demonstrated both TGF-alpha mRNA and protein. The vast majority of eosinophils present in the periapical granulomas and cysts also demonstrated TGF-beta 1 mRNA and protein. Other cells producing TGF-beta 1 were lymphocytes, fibroblasts, and monocytes. The presence of wound repair cytokines, such as TGF-alpha and TGF-beta 1, suggests a mechanism by which the host inflammatory response may participate in the repair and remodeling of periapical tissues.

Adult↗

PubMed1999

Successful treatment of chloral hydrate cardiac toxicity with propranolol.

A case of chloral hydrate overdose causing resistant ventricular arrhythmias is presented. Our case and other case reports suggest that chloral hydrate-induced arrhythmias are resistant to standard antiarrhythmic agents and that intravenous beta blockers should be the firstline treatment for these arrhythmias.

Adult↗

PubMed1999

Eosinophil ablation and tumor development.

Tissue eosinophilia in squamous cell carcinoma has long been recognized; however, the role of eosinophils in tumor development remains unclear. Studies have reported both favorable and unfavorable prognoses for patients with tumors exhibiting tumor-associated tissue eosinophilia (TATE). This study seeks to elucidate the potential role of the eosinophil in squamous cell carcinoma development and provide an experimental model for future studies. The carcinogen-induced hamster oral cancer model was found to fulfill these objectives. Eosinophils progressively infiltrate into this carcinogen-induced oral cancer model. We now demonstrate that TATE is completely abolished by the use of an anti-interleukin-5 monoclonal antibody (mAb) preparation, TRFK-5. Clinical observations revealed that TRFK-5-treated hamsters exhibited smaller tumor burden and delayed onset of tumor development. The results suggest that anti-interleukin-5 antibody treatment may delay and/or inhibit tumor development, and that eosinophils may have a tumor-promoting role.

Animals↗

PubMed1999

Messenger RNA level and protein localization of transforming growth factor-beta1 in experimental tooth movement in rats.

Transforming growth factor-beta1 (TGF-beta1) is known to be associated with local bone remodeling. We hypothesize that TGF-beta1 is induced in bone and regulates adaptive alveolar bone modeling during tooth movement. To test this hypothesis, we examined the steady-state mRNA level of TGF-beta1 and the protein localization of TGF-beta1 and its type II receptor (TbetaR-II) during experimental tooth movement. Maxillary right molars, M1, M2 and M3, of rats were moved palatally for 1, 3 and 7 d by a finger coil spring anchored to the upper incisors. The contralateral side was used as a control. After 3 d of tooth movement, intense immunostaining for TGF-beta1 and TbetaR-II was observed in cuboidally shaped osteoblasts in the tension zone, and in bone-resorbing osteoclasts in the compression zone. On the control side, few active osteoblasts and osteoclasts were observed. Reverse transcriptase-competitive polymerase chain reaction revealed significant increases in TGF-beta1 mRNA in alveolar bone cells on the tooth movement side on day 3 and day 7. Taken together, our data indicate that TGF-beta1 is induced during tooth movement and we propose that this may regulate adaptive alveolar bone modeling.

Alveolar Process↗

PubMed1999

Risk factors of delayed extubation, prolonged length of stay in the intensive care unit, and mortality in patients undergoing coronary artery bypass graft with fast-track cardiac anesthesia: a new cardiac risk score.

BACKGROUND: Risk factors of delayed extubation, prolonged intensive care unit (ICU) length of stay (LOS), and mortality have not been studied for patients administered fast-track cardiac anesthesia (FTCA). The authors' goals were to determine risk factors of outcomes and cardiac risk scores (CRS) for CABG patients undergoing FTCA. METHODS: Consecutive CABG patients undergoing FTCA were prospectively studied. Outcome variables were delayed extubation > 10 h, prolonged ICU LOS > 48 h, and mortality. Univariate analyses were performed followed by multiple logistic regression to derive risk factors of the three outcomes. Simplified integer-based CRS were derived from logistic models. Bootstrap validation was performed to assess and compare the predictive abilities of CRS and logistic models for the three outcomes. RESULTS: The authors studied 885 patients. Twenty-five percent had delayed extubation, 17% had prolonged ICU LOS, and 2.6% died. Risk factors of delayed extubation were increased age, female gender, postoperative use of intraaortic balloon pump, inotropes, bleeding, and atrial arrhythmia. Risk factors of prolonged ICU LOS were those of delayed extubation plus preoperative myocardial infarction and postoperative renal insufficiency. Risk factors of mortality were female gender, emergency surgery, and poor left ventricular function. CRSs were modeled for the three outcomes. The area under the receiver operating characteristic curve for the CRS-logistic models was not significantly different: 0.707/0.702 for delayed extubation, 0.851/0.855 for prolonged ICU LOS, and 0.657/0.699 for mortality. CONCLUSION: In CABG patients undergoing FTCA, the authors derived and validated risk factors of delayed extubation, prolonged ICU LOS, and mortality. Furthermore, they developed a simplified CRS system with similar predictive abilities as the logistic models.

Aged↗

PubMed1999

Utilization of intensive care unit days in a Canadian medical-surgical intensive care unit.

OBJECTIVES: To analyze the utilization of intensive care unit (ICU) days in a Canadian medical-surgical ICU and to identify ICU patients with prolonged ICU length of stay (LOS). DESIGN: Prospective descriptive study. SETTING: A Canadian tertiary care medical-surgical ICU. PATIENTS: Consecutive patients admitted to an adult medical-surgical ICU. Neurosurgical, cardiac surgical, and coronary care unit patients were excluded. MEASUREMENTS: For each ICU admission, patient demographics, diagnosis, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, ICU LOS, and hospital mortality were collected. The patients' risk of death was calculated using the APACHE II equation. Admissions were stratified by ICU LOS into four groups: 1 to 2, 3 to 6, 7 to 13, and > or = 14 days. Among the four LOS groups, the number of ICU days and observed and predicted death rates were compared. Admissions were also stratified by risk of death into five probability range quintiles. Among the five risk groups, ICU LOS was compared between survivors and nonsurvivors. RESULTS: A total of 1,960 admissions utilized 9,298 ICU days. ICU LOS (mean +/- SEM) was 4.74 +/- 0.2 (median, 2; range, 1 to 178) days. Short-stay patients (ICU LOS < or = 2 days) accounted for 60.3% of total admissions but consumed only 16.4% of total ICU days. Long-stay patients (ICU LOS > or = 14 days) accounted for 7.3% of total admissions but consumed 43.5% of total ICU days. Among the long-stay patients, the most common reasons for admission were pneumonia, multiple trauma, neuromuscular weakness, and septic shock. The mortality for long-stay patients approached 50%. When analyzed by patients' mortality risks, those with a risk of death >0.8 (predicted to die) or <0.2 (predicted to live) whose outcomes were opposite to that predicted had twice the ICU LOS compared with patients whose outcomes were consistent with prediction. CONCLUSION: In a Canadian medical-surgical ICU, patients with ICU LOS > or = 14 days accounted for 7.3% of total admissions but consumed 43.5% of total ICU days. Identification of patients with prolonged ICU LOS who would ultimately die in the ICU may lead to earlier withdrawal of therapy in these patients, resulting in a substantial reduction in suffering and cost savings. In our study population, outcome prediction using the APACHE II equation did not provide sufficient power to accurately discriminate between nonsurvivors and survivors.

APACHE↗

PubMed1999

A quantitative assessment of how Canadian intensivists believe they utilize oxygen in the intensive care unit.

OBJECTIVES: To investigate attitudes and practices regarding oxygen therapy in intensive care units (ICUs) and to devise quantitative descriptive indices. SETTING: Canadian university-affiliated adult ICUs. PARTICIPANTS: Fifty-two medical directors of ICUs in 48 institutions. INTERVENTION: Structured postal questionnaire returned by 48 participants. MEASUREMENTS AND MAIN RESULTS: Attitudes, beliefs, and stated practices relating to oxygen use in ICUs were determined. Novel descriptors S-50min (minutes of oxygen saturation [Sao2] acceptable to >50% of respondents), F-50max (maximum F(IO)2 above which <50% of respondents would increase F(IO)2), and F-50min (minimum F(IO)2 below which <50% of respondents would decrease F(IO)2) were determined. All respondents believed that oxygen toxicity was a concern. Twenty-nine percent of respondents indicated that they did not always assess tissue oxygenation in critical cases. A stepwise reduction in acceptance of progressive desaturation and increasing duration of hypoxemia was found. Presented with a stable patient with Sao2 of 98%, the maximum level of F(IO)2 above which respondents stated that they would not increase the F(IO)2 was 0.41+/-0.17 (mean +/- SD). For stable patients with Sao2 of 85%, the minimum F(IO)2 below which respondents would not reduce F(IO)2 was 0.59+/-0.23 (mean +/- SD). F-50max was 0.8 vs. 0.5 for Sao2 of 80%-85% vs. 85%-90%, respectively; F-50min was 0.6 vs. 0.21 for Sao2 of 90%-95% vs. 95%-100%, respectively. CONCLUSIONS: Considerable variation exists in the attitudes, beliefs, and stated practices relating to the management of oxygen therapy in the ICU. These data are amenable to quantitative description and illustrate the necessity for documentation of actual practice and development of support systems for decision-making in this and similar areas.

Adult↗

PubMed1999

Epidermal growth factor receptor (EGFR) biology and human oral cancer.

Dysregulation of the epidermal growth factor receptor (EGFR) is one of the most frequently studied molecular events leading to oral carcinogenesis. Overexpression of EGFR is a common event in many human solid tumors. Elevated levels of EGFR mRNA in human cancer occur with and without gene rearrangement. Structural alterations in the receptor can also result in the dysregulation of the EGFR pathway. EGFR overexpression without gene re-arrangement is frequently observed in human oral cancers. However, little is known whether structural alterations in the receptor or perturbations in the EGFR pathway contribute to oral carcinogenesis. Several preliminary studies suggest that EGFR-targeted therapeutic approaches might be successful in controlling oral cancer.

ErbB Receptors↗

PubMed1999

Olanzapine: a basic science update.

Olanzapine, an atypical antipsychotic, has a broad receptor binding profile, which may account for its pharmacological effects in schizophrenia. In vitro receptor binding studies showed a high affinity for dopamine D2, D3, and D4 receptors; all 5-HT2 receptor subtypes and the 5-HT6 receptor; muscarinic receptors, especially the M1 subtype: and alpha 1-adrenergic receptors. In vivo studies showed that olanzapine had potent activity at D2 and 5-HT2A receptors, but much less activity at D1 and muscarinic receptors, and that it inhibited dopaminergic neurons in the A10 but not the A9 tract, suggesting that this agent will not cause extrapyramidal side-effects (EPS). Microdialysis studies showed that olanzapine increased the extracellular levels of norepinephrine and dopamine, but not 5-HT, in the prefrontal cortex, and increased extracellular dopamine levels in the neostriatum and nucleus accumbens, areas of the brain associated with schizophrenia. Studies of gene expression showed that olanzapine 10 mg/kg also increased Fos expression in the prefrontal cortex, the dorsolateral striatum, and the nucleus accumbens. These findings are consistent with the effectiveness of olanzapine on both negative and positive symptoms and suggest that, with careful dosing, olanzapine should not cause EPS.

Animals↗

PubMed1998

Reduction of ornithine decarboxylase antizyme (ODC-Az) level in the 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis model.

Ornithine decarboxylase (ODC) activity is elevated in and necessary for oral carcinogenesis, but the mechanism for its deregulation is unclear. Using subtractive hybridization, a 1029 bp full-length cDNA encoding a 222 amino acid open reading frame has been isolated from normal hamster oral keratinocytes. The hamster cDNA is homologous to the human, mouse and rat ornithine decarboxylase antizyme gene (ODC-Az). The hamster ODC-Az gene demonstrated a restriction fragment length polymorphism (RFLP) upon Southern blot analysis comparing normal and tumor hamster genomic DNA. Northern blot analysis revealed that normal hamster oral keratinocytes express readily detectable level of ODC-Az mRNA. Malignant oral keratinocytes demonstrate reduced expression of the ODC-Az mRNA. In contrast, malignant hamster oral keratinocytes have elevated ODC mRNA levels and lengthened ODC protein half-life when compared to the normal counterparts. This was corroborated by direct measurement of ODC enzymatic activity. These data support the hypothesis that the reduced and/or loss of expression and function of the ODC-Az gene is an important event for the early de-regulation of cellular proliferation during oral tumor development.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1998

IL-4-dependent regulation of TGF-alpha and TGF-beta1 expression in human eosinophils.

TGFs play important roles in wound healing and carcinogenesis. We have previously demonstrated that eosinophils infiltrating into different pathologic processes elaborate TGF-alpha and TGF-beta1. Eosinophils infiltrating hamster cutaneous wounds were found to express TGFs sequentially. In this study, we examined the biologic mediators that may regulate the expression of TGF-alpha and -beta1 by eosinophils. Eosinophils were isolated from the peripheral blood of healthy donors and cultured in the absence or presence of IL-3, IL-4, and IL-5. Cells were analyzed by in situ hybridization and immunohistochemistry. Supernatants from these cultures were assayed for secreted TGF-alpha and TGF-beta1 using TGF-specific ELISAs. IL-3, IL-4, and IL-5 independently up-regulated TGF-beta1 mRNA and product expression by eosinophils in all donors. Interestingly, TGF-alpha production by eosinophils was up-regulated by IL-3 and IL-5 but was down-regulated by IL-4. Consistent with the ability of IL-4 to regulate eosinophil responses, IL-4 signaling molecules are present in human eosinophils. The observation that IL-4 can differentially regulate the expression of TGF-alpha and TGF-beta1 suggests that IL-4 may serve as a physiologic molecular switch of TGF expression by the infiltrating eosinophils in wound healing and carcinogenesis.

Adult↗

PubMed1998

Optimized conditions for gene transfection into the human eosinophilic cell line EoL-1 by electroporation.

Eosinophils are emerging as an increasingly important cell in the immunoregulatory network of normal and pathological processes. No studies has yet described optimized experimental strategies to transfect DNA into human eosinophils. Using a frequently employed in vitro model of human eosinophil, the EoL-1 cells, we now described the optimal transfection of DNA into these cells by electroporation. Our results indicate that electroporation can efficiently and reproducibly transfect DNA into EoL-1 cells. Optimal electroporation conditions consist of the use of 1 X RPMI medium 1640 with 10% FBS, voltage setting at 275 V, 1150 microF capacitance, 40 mg of DNA and 4.0 X 10(7) cells/ml per electroporation in a total volume of 0.5 ml in 0.4 cm gap cuvettes. These conditions may be a useful protocol for transfecting eosinophil cell lines.

DNA↗

PubMed1998

Cloning, mapping, expression, function, and mutation analyses of the human ortholog of the hamster putative tumor suppressor gene Doc-1.

doc-1 is a putative tumor suppressor gene isolated and identified from the hamster oral cancer model. Here, we report the molecular cloning and the functional characterization of the human ortholog of the hamster doc-1 gene. Human doc-1 cDNA is 1.6 kilobase pairs in length and encodes for a 115-amino acid polypeptide (12.4 kDa, pI 9. 53). Sequence analysis showed 98% identity between human and hamster doc-1 protein sequences. DOC-1 is expressed in all normal human tissues examined. In oral keratinocytes, expression of DOC-1 is restricted to normal oral keratinocytes. By immunostaining of normal human mucosa, DOC-1 is detected in both the cytoplasm and nuclei of basal oral keratinocytes; while in suprabasilar cells, it is primarily found in the nuclei. Human oral cancers in vivo did not exhibit immunostaining for DOC-1. Like murine DOC-1, human DOC-1 associates with DNA polymerase alpha/primase and mediates the phosphorylation of the large p180 catalytic subunit, suggesting it may be a potential regulator of DNA replication in the S phase of the cell cycle. Using a human doc-1 cosmid as a probe, human doc-1 is mapped to chromosome 12q24. We identified four exons in the entire human doc-1 gene and determined the intron-exon boundaries. By polymerase chain reaction and direct sequencing, we examined premalignant oral lesion and oral cancer cell lines and found no intragenic mutations.

Amino Acid Sequence↗

PubMed1998

IS1491 from Pseudomonas alcaligenes NCIB 9867: characterization and distribution among Pseudomonas species.

A new insertion sequence, IS1491, has been cloned and sequenced. The 2489-bp IS1491 was isolated from a Pseudomonas alcaligenes NCIB 9867 (strain P25X) 4.8-kb PstI chromosomal fragment. IS1491 is flanked by an imperfect inverted repeat of 23 bp and carries two overlapping open reading frames, ORF1 and ORF2. Both ORF1 and ORF2 displayed homology to the IstA-like and IstB-like transposases encoded by the IS21 family of insertion sequences, which include two IS elements previously isolated from P. alcaligenes P25X, IS1474, and IS1475 (Yeo, C. C., and Poh, C. L. (1997). FEMS Microbiol. Lett. 149, 257-263). Transposition assays showed that IS1491 transposed at a frequency of approximately 1.4 x 10(-6). Transposition of IS1491 into the target pRK415 replicon was observed but when ORF2 was disrupted, a fusion between the donor and target replicons was detected. IS1491-like sequences were detected in total DNA of Pseudomonas putida NCIB 9869 (strain P35X), Pseudomonas aeruginosa, Pseudomonas stutzeri, Pseudomonas syringae, Pseudomonas mendocina, Comomonas acidovorans, and Comomonas testosteroni by hybridization with IS1491 DNA.

Amino Acid Sequence↗

PubMed1998

The anaesthesia consult clinic: does it matter which anaesthetist sees the patient?

PURPOSE: The objectives of this multicentre survey were: first to ascertain whether the preoperative evaluation performed by anaesthetists in the preadmission anaesthesia consultation clinic (PACC) is influenced by the knowledge that they will or will not be the patient's attending anaesthetist; and second to determine the agreement among anaesthetists with regard to investigations requested. METHODS: A postal survey was designed in two different versions, equal numbers of which were sent to 522 anaesthetists in 39 Canadian hospitals. The anaesthetists contacted were asked to consider how they would investigate two hypothetical patients in a PACC. One version of the survey stated that they would be the attending anaesthetist for the first patient, but not for the second patient (group A). In the second version the situation was reversed (group B). RESULTS: A total of 281 eligible replies were received. For each of the two patients the decision to order an echocardiogram, cardiac stress test, arterial blood gas analysis, pulmonary function tests, or internal medicine referral was not affected by the knowledge that the respondent would or would not be the patient's attending anaesthetist. Within each of the two groups there was very little consensus with regard to the ordering of laboratory tests. CONCLUSION: The extent of investigation in the PACC scenarios was not affected by knowledge of whether or not the consulting anaesthetist would be the attending anaesthetist in the operating room. However, there was minimal agreement among anaesthetists concerning the preoperative evaluation of the patients, regardless of who would be the anaesthetist on the day of operation. Efficiency in preoperative evaluation could be increased if anaesthetists saw their own patients in the PACC, or if clinical guidelines for patient assessment were introduced by departments.

Anesthesia↗

PubMed1998

Predictors of hospital mortality and mechanical ventilation in patients with cervical spinal cord injury.

PURPOSE: The objective of this study was to identify predictors of death and mechanical ventilation in patients with traumatic cervical spinal cord injury. METHODS: From 1981 to 1994, 72 patients with traumatic cervical spinal cord injury resulting in neurological deficits were identified in this retrospective study. For each patient, neurological and associated injuries, physiological variables, complications, hospital mortality and the need for mechanical ventilation were recorded. Univariate and multivariate logistic regression analyses were done to identify predictors of mortality and the need for mechanical ventilation. RESULTS: Fifteen patients (21%) died in the first three months after injury. Univariate analyses identified age, heart disease, neurological level at C4 and above, GCS < or = 13, forced vital capacity and cough, to be associated with mortality. Multivariate logistic regression identified age (P = 0.01), neurological level (P = 0.03) and GCS (P = 0.05) as independent predictors of mortality. In 41 patients (57%), the lungs were mechanically ventilated. Univariate analyses identified. The following predictors of the need for mechanical ventilation: neurological level at C5 and above, complete cord lesions, copious sputum, pneumonia and lung collapse. Multivariate logistic regression identified copious sputum (P = 0.01) and pneumonia (P = 0.01) as independent predictors of the need for mechanical ventilation. CONCLUSION: Age, neurological level and GCS are independent predictors of mortality in patients with traumatic cervical spinal cord injury. Copious sputum and pneumonia are independent predictors of the need for mechanical ventilation.

Adolescent↗

PubMed1998

Olanzapine increases in vivo dopamine and norepinephrine release in rat prefrontal cortex, nucleus accumbens and striatum.

The in vivo effects of olanzapine on the extracellular monoamine levels in rat prefrontal cortex (Pfc), nucleus accumbens (Acb) and striatum (Cpu) were investigated by means of microdialysis. Sequential doses of olanzapine at 0.5, 3 and 10 mg/kg (s.c.) dose-dependently increased the extracellular dopamine (DA) and norepinephrine (NE) levels in all three brain areas. The increases appeared 30 min after olanzapine administration, reached peaks around 60-90 min and lasted for at least 2 h. The highest DA increases in the Acb and Cpu were induced by olanzapine at 3 mg/kg but at 10 mg/kg in the Pfc. The peak DA increase in the Pfc (421% +/- 46 of the baseline) was significantly larger than those in the Acb (287% +/- 24) and Cpu (278% +/- 28). Similarly, the highest NE increase in the Pfc (414% +/- 40) induced by 10 mg/kg olanzapine was larger than those in the Acb (233% +/- 39) and Cpu (223% +/- 24). The DA and NE increases in the Pfc induced by olanzapine at 3 and 10 mg/kg (s.c.) were slightly larger than those induced by clozapine at the same doses. In contrast, haloperidol (0.5 and 2 mg/kg, s.c.) did not change Pfc DA and NE levels. Extracellular levels of a DA metabolite, DOPAC, and tissue concentrations of a released DA metabolite, 3-methoxytyramine, were also increased by olanzapine, consistent with enhanced DA release. However, olanzapine at the three sequential doses did not alter the extracellular levels of either 5-HT or its metabolite, 5-HIAA, in any of the three brain areas. In conclusion, the present studies demonstrate that in the case of sequential dosing olanzapine more effectively enhances DA and NE release in the Pfc than in the subcortical areas, which may have an impact on its atypical antipsychotic actions.

Animals↗