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Biomedical subjects

C W Wong

Publications and source records attributed to C W Wong.

At least 37 records · Page 2Linked to original sources
PubMed2000

PECAM-1/CD31 trans-homophilic binding at the intercellular junctions is independent of its cytoplasmic domain; evidence for heterophilic interaction with integrin alphavbeta3 in Cis.

PECAM-1/CD31 is a cell adhesion and signaling molecule that is enriched at the endothelial cell junctions. Alternative splicing generates multiple PECAM-1 splice variants, which differ in their cytoplasmic domains. It has been suggested that the extracellular ligand-binding property, homophilic versus heterophilic, of these isoforms is controlled by their cytoplasmic tails. To determine whether the cytoplasmic domains also regulate the cell surface distribution of PECAM-1 splice variants, we examined the distribution of CD31-EGFPs (PECAM-1 isoforms tagged with the enhanced green fluorescent protein) in living Chinese hamster ovary cells and in PECAM-1-deficient endothelial cells. Our results indicate that the extracellular, rather than the cytoplasmic domain, directs PECAM-1 to the cell-cell borders. Furthermore, coculturing PECAM-1 expressing and deficient cells along with transfection of CD31-EGFP cDNAs into PECAM-1 deficient cells reveal that this PECAM-1 localization is mediated by homophilic interactions. Although the integrin alphavbeta3 has been shown to interact with PECAM-1, this trans-heterophilic interaction was not detected at the borders of endothelial cells. However, based on cocapping experiments performed on proT cells, we provide evidence that the integrin alphavbeta3 associates with PECAM-1 on the same cell surface as in a cis manner.

Alternative Splicing↗
PubMed2000

Effect of the grapefruit flavonoid naringin on pharmacokinetics of quinine in rats.

The effect of the grapefruit flavonoid naringin, an inhibitor of CYP3A4, on the pharmacokinetics of quinine in rats after oral or intravenous (i.v.) dosing of quinine was investigated. Female Wistar rats (wt 190-220 g) were used in two separate studies, i.e. oral and i.v. administration of quinine. The animals were divided into two groups, one served as control and the other group was pretreated with 25 mg/kg naringin once a day for 7 consecutive days before the pharmacokinetic study. On the study day, quinine (25 mg/kg) was administered to the rats by either the oral or i.v. route. Blood samples were collected at different times, up to 6 h after quinine administration. Plasma quinine concentration was assayed by HPLC. Pretreatment with naringin did not cause any significant change in the pharmacokinetics of quinine after the i.v. dose. However pretreatment with naringin led to a 208% increase in peak plasma concentration (Cmax), a 93% increase in time to reach Cmax (tmax), and a 152% increase in the area under the plasma concentration-time curve (AUC) of quinine after oral administration. Consequently, the oral bioavailability of quinine was significantly increased (p < 0.05) from 17% (control) to 42% after pretreatment with naringin. There was no significant difference in the elimination half-life (t(1/2)beta) of quinine between the two groups. These results suggest that pretreatment with the grapefruit flavonoid naringin is associated with increased oral bioavailability of quinine in rats.

Administration, Oral↗
PubMed2000

Metastatic solitary fibrous tumor of the meninges. Case report.

Solitary fibrous tumor (SFT) is a unique tumor composed of interstitial dendritic cells that was first described in the thorax and subsequently reported in diverse organs. Extrathoracic SFTs are predominantly benign but rare malignant cases have been documented. In the nervous system, SFT has been described as a meningeal lesion although all 14 previously reported cases were benign. The authors report the first case of a meningeal SFT occurring in a 55-year-old woman. The tumor first presented as a meningeal lesion that after three recurrences over a 10-year period metastasized to the soft tissues and lungs. The potentially malignant nature of cranial SFTs, especially those with atypical histological features and high mitotic counts, should be recognized.

Female↗
PubMed1999

Left stellate stimulation increases left ventricular ejection fraction in patients with essential palmar hyperhidrosis.

Left stellate stimulation increases cardiac contractility, heart rate, systolic blood pressure, and QT interval in experimental animals. To see if these changes occur in humans, we stimulated the left stellate ganglia with a monopolar coagulation power of 5 W in 10 patients with palmar hyperhidrosis, axillar hyperhidrosis, or both. We also stimulated the right stellate ganglia of the other 10 patients. The mean left ventricular ejection fraction (LVEF, measured with M-mode echocardiography), QT interval, heart rate and systolic blood pressure of the baseline were 54.72%, 403 ms, 65/min, and 115 mmHg, whereas those after 45 s of left stellate stimulation were 62.84%, 434 ms, 73/min, and 123 mmHg respectively. We compared these data with those of the baseline and the two-tailed P values were 0.005 for both LVEF and QT interval, 0.052 for heart rate, and 0.050 for systolic blood pressure respectively (Wilcoxon Matched-Pairs Signed-Ranks Test). The corresponding P-values for those of the right stellate stimulation were 0.721, 0.203, 0.260, and 0.326 respectively. All these suggest that the left stellate ganglia predominate the right ones in affecting LVEF, QT interval, heart rate and systolic blood pressure in humans, that left stellate stimulation increases LVEF and prolongs QT interval significantly, and that left stellate stimulation accelerates heart rate and elevates systolic blood pressure marginally.

Adult↗
PubMed1999

Chinese Frost Multidimensional Perfectionism Scale: a validation and prediction of self-esteem and psychological distress.

Recent research has shown that perfectionism is an important psychological variable in explaining various disorders. This study evaluated (a) the factor structure and psychometric properties of the Chinese Frost Multidimensional Perfectionism Scale (CFMPS) and (b) the relative predictive power of its subscales for self-esteem and psychological distress, including depressive, anxiety, and stress symptoms. Nine hundred and forty-seven Chinese adolescents from Hong Kong between 13 and 18 years of age participated in the study. Results indicated that five of the original six factors emerged in the factor analysis. The CFMPS and its subscales were found to have satisfactory internal consistencies. Replicating and extending previous findings, the factors "Concern over Mistakes" and "Doubt about Action" accounted for most of the variances of self-esteem and psychological distress. The factor "Organization" might have positive value on psychological health. Possible cultural influence on the development of perfectionism and limitations of the study are discussed.

Adolescent↗
PubMed1999

Far lateral approach with intraoperative ultrasound Doppler identification of the vertebral artery.

A 69-year-old woman presented with right hemiparesis and magnetic resonance imaging revealed a meningioma at the ventral aspect of the foramen magnum. We used a retromastoid curvilinear incision down the lateral aspect of the neck to expose the semispinalis and other muscles. Guided by ultrasound to avoid damage to the vertebral artery beneath the semispinalis, we incised the semispinalis muscle in a U-shape that hinged at the retromastoid curvilinear incision with its one limb along the border of the foramen magnum and the other limb along the posterior arch of the atlas. The other muscles were divided in line with the curvilinear incision and retracted posteriorly with the bulk of semispinalis to expose the bones, not disturbing the U-shaped piece of semispinalis that covered the vertebral artery. Similarly guided by ultrasound, we performed far lateral suboccipital craniectomy and laminectomy, exposed the dura above and below the dural entry of the vertebral artery, opened the dura cephalad and caudal to the dural entry of the vertebral artery, and excised the tumor. This method provided adequate exposure to the lateral aspect of the cranio-vertebral junction and minimized the risks of dissecting the whole extradural segment of vertebral artery. It requires more cases to determine whether the results of this patient can be generalized.

Aged↗
PubMed1999

Data convergence in a brain model.

Assuming the existence of encoding synapses that record presynaptic axonal 'on-off' pattern as the content of memory, the author has presented a brain model. In this brain model, the synapses of a neuron work like a static random access memory (RAM) that may encode 2 the power of 10,000 'on-off' patterns, the cell body like a central processing unit (CPU) that produces a signal of 1 or 0 in response to different presynaptic axonal 'on-off' patterns, and the axon like a data bus to form synapse with another neuron. Accordingly, the brain is analogous with a computer made of serial static RAMs amid 14 billions of parallel processing CPUs. Such a brain model converges data with each tier of computation, because there are always more input presynaptic 'on-off' patterns than output axonal 'on-off' patterns in a cortical area. The more computations of the data from the primary perceptive cortices, the more likely the data involving the synapses of central cortices, and the more abstract the content of the memory--hence, in the retrieval of memory, parts of the 'on-off' patterns of the original stimulus may lead to the converged, abstract memory. This can be the mechanism of pattern recognition in the brain.

Brain↗
PubMed1999

Surface laser scanning of the cleft palate deformity--validation of the method.

Innovations in laser technology have led to the development of three-dimensional surface laser digitisation techniques capable of registering surface topology accurately. The clinical application of this technology in cleft palate documentation requires validation of the technique. This study determined the reliability of the surface laser scanning technique and assessed the reliability of interactive three-dimensional landmark localization. Original and duplicate plaster models of an infant with a complete unilateral cleft lip and palate were digitised with the Cyberware 3030R-HIREZ surface laser scanner. Seven anatomic landmarks were marked permanently on the palatal surface of the duplicate model only, which acted as visual cues for landmark localisation. Each model was scanned ten times serially, and ten composite three-dimensional images were obtained for each. On-line interactive computer landmark localisation permitted the assessment of variance for the x, y and z coordinates of each landmark. The precision of the laser scanning technique was found to be less than 0.06 mm in all three axes. Anatomic landmarks with the clearest visual cue were the least variable after ten rounds of scanning. Significant differences existed between visually aided and non-aided landmark localisation (P < 0.05). While landmarks could be localised repeatedly without the aid of a visual marker, landmarks well defined by a clearly visible visual cue on the three-dimensional image were more reliable.

Cleft Palate↗
PubMed1998

Components of the SMRT corepressor complex exhibit distinctive interactions with the POZ domain oncoproteins PLZF, PLZF-RARalpha, and BCL-6.

Many transcription factors function by repressing gene transcription. For a variety of these transcription factors the ability to physically recruit auxiliary proteins, denoted corepressors, is crucial for the ability to silence gene expression. We and others have previously implicated the SMRT corepressor in the actions of the PLZF transcription factor and in the function of its oncogenic derivative, PLZF-retinoic acid receptor (RARalpha), in promyelocytic leukemia. We report here that PLZF, and a structurally similar transcriptional repressor, BCL-6, can interact with a variety of corepressor proteins in addition to SMRT, including the mSin3A protein and (for PLZF) histone deacetylase-1. Unexpectedly, these additional interactions with corepressor components are nonequivalent for these otherwise similar oncoproteins, suggesting that transcriptional repression by BCL-6 and by PLZF may differ in mechanism. Furthermore, we demonstrate that the oncogenic PLZF-RARalpha chimera lacks several important corepressor interaction sites that are present in the native PLZF protein. Thus the t(11;17) translocation that creates the PLZF-RARalpha chimera generates an oncoprotein with potentially novel regulatory properties distinct from those of either parental protein. Our results demonstrate that otherwise similar transcription factors can differ notably in their interactions with the corepressor machinery.

Binding Sites↗
PubMed1998

Histone deacetylase associated with mSin3A mediates repression by the acute promyelocytic leukemia-associated PLZF protein.

The PLZF gene was identified first by its fusion with the retinoic acid receptor alpha gene in the t(11;17) translocation associated with a retinoic acid resistant form of acute promyelocytic leukemia (APL). It encodes a krüppel-like zinc finger protein with a POZ domain shared with a subset of regulatory proteins including the BCL6 leukemogenic protein. PLZF, like BCL6, strongly represses transcription initiated from different promoters. Here we show that PLZF associates in vitro and in vivo with the Mad co-repressor mSin3A and the histone deacetylase HDAC1. Two domains in PLZF and the PAH1 structure of mSin3A mediate these interactions. Trichostatin A, a specific inhibitor of histone deacetylases, significantly reduces PLZF repression. These data strongly suggest that, like nuclear receptors and Mad, PLZF represses transcription by recruiting a histone deacetylase through the SMRT-mSin3-HDAC co-repressor complex. We also show that BCL6 associates with HDAC1 indicating that this type of regulation might be common to POZ/Zinc finger proteins involved in human leukemias. This work supports a role for deregulated histone deacetylation in the development of both lymphoid and myeloid neoplasia in human and suggests that targeted histone deacetylase inhibitors may be useful for treatment of certain types of malignancies.

Binding Sites↗
PubMed1998

Variation in the immune status of two Australian pig breeds.

OBJECTIVE: To investigate the variation in immune competence of two Australian pig breeds. DESIGN: A panel of immune tests were used to assess breed and sire differences in weaner piglets of Large White and Duroc breeds. PROCEDURE: All piglets were immunised against porcine leptospirosis. Blood samples were taken for studies on lymphocyte phenotypes, mitogenic responses of blood cells and serological analysis. RESULTS: Significantly larger blood leucocyte numbers were found in Large White piglets compared with Duroc piglets after vaccinations. No significant difference in concanavalin A induced blood cell proliferation was found between these two breeds before or after vaccinations. Some significant breed variation in blood lymphocyte phenotypes was found. While the age-related changes of lymphocyte phenotypes were similar for the two breeds, the Large White breed had significantly larger numbers of CD2+ and CD4+ cells than the Duroc breed after the two vaccinations. There were also significant sire effects on CD8+ cells within the Large White breed after the first vaccination. No significant breed difference was detectable in serum IgG concentrations but sire differences within each breed before the primary vaccination were found. The serum antibody response to vaccination against leptospirosis was generally small, and showed no variations due to either breed or sire. No gender effects were found during the entire study. CONCLUSION: The study demonstrated significant differences in some important immune components of the pig breeds studied. This may in turn indicate the variation in their immune competence or disease resistance. However, further investigation into the heritability and correlation with specific immune responses is required.

Agglutination Tests↗
PubMed1998

Transcriptional silencing is defined by isoform- and heterodimer-specific interactions between nuclear hormone receptors and corepressors.

Nuclear hormone receptors are ligand-regulated transcription factors that play critical roles in metazoan homeostasis, development, and reproduction. Many nuclear hormone receptors exhibit bimodal transcriptional properties and can either repress or activate the expression of a given target gene. Repression appears to require a physical interaction between a receptor and a corepressor complex containing the SMRT/TRAC or N-CoR/RIP13 polypeptides. We wished to better elucidate the rules governing the association of receptors with corepressors. We report here that different receptors interact with different domains in the SMRT and N-CoR corepressors and that these divergent interactions may therefore contribute to distinct repression phenotypes. Intriguingly, different isoforms of a single nuclear hormone receptor class also differ markedly in their interactions with corepressors, indicative of their nonidentical actions in cellular regulation. Finally, we present evidence that combinatorial interactions between different receptors can, through the formation of heterodimeric receptors, result in novel receptor-corepressor interactions not observed for homomeric receptors.

Amino Acid Sequence↗
PubMed1998

Transcriptional repression by the SMRT-mSin3 corepressor: multiple interactions, multiple mechanisms, and a potential role for TFIIB.

A variety of eukaryotic transcription factors, including the nuclear hormone receptors, Max-Mad, BCL-6, and PLZF, appear to mediate transcriptional repression through the ability to recruit a multiprotein corepressor complex to the target promoter. This corepressor complex includes the SMRT/N-CoR polypeptides, mSin3A or -B, and histone deacetylase 1 or 2. The presence of a histone-modifying activity in the corepressor complex has led to the suggestion that gene silencing is mediated by modification of the chromatin template, perhaps rendering it less accessible to the transcriptional machinery. We report here, however, that the corepressor complex actually appears to exhibit multiple mechanisms of transcriptional repression, only one of which corresponds with detectable recruitment of the histone deacetylase. We provide evidence instead of an alternative pathway of repression that may be mediated by direct physical interactions between components of the corepressor complex and the general transcription factor TFIIB.

Animals↗
PubMed1998

Signaling by tyrosine kinases negatively regulates the interaction between transcription factors and SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) corepressor.

Nuclear hormone receptors are hormone-regulated transcription factors that bind to specific sites on DNA and modulate the expression of adjacent target genes. Many nuclear hormone receptors display bimodal transcriptional properties; thyroid hormone receptors, for example, typically repress target gene expression in the absence of hormone, but activate target gene expression in the presence of hormone. The ability to repress is closely linked to the ability of the apo-receptor to physically bind to auxiliary corepressor proteins denoted SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) and N-CoR (nuclear receptor corepressor), which, in turn, help mediate the actual molecular events involved in transcriptional silencing. We report here that repression by thyroid hormone receptors can be regulated not only by cognate hormone, but also by certain tyrosine kinase signal transduction pathways, such as that represented by the epidermal growth factor-receptor. Activation of tyrosine kinase signaling leads to inhibition of T3R-mediated repression with relatively little effect on activation. These effects appear to be mediated by a kinase-initiated disruption of the ability of T3R to interact with SMRT corepressor. Intriguingly, tyrosine kinase signaling similarly disrupted the interactions of SMRT with v-Erb A, with retinoic acid receptors, and with PLZF, a nonreceptor transcriptional repressor. We conclude that tyrosine kinase signaling exerts potentially important regulatory effects on transcriptional silencing mediated by a variety of transcription factors that operate through the SMRT corepressor complex.

Animals↗
PubMed1997

The second thoracic sympathetic ganglion determines palm skin temperature in patients with essential palmar hyperhidrosis.

Sympathectomy of the second (T2) and third (T3) thoracic ganglion is frequently performed for essential palmar hyperhidrosis and occasionally performed, in addition to stellectomy, for idiopathic Raynaud's disease. The increased palm skin temperature after the operation probably results from increased skin perfusion. To determine whether it was possible to limit the extent of sympathectomy for these patients, we recorded palm skin temperature after electric stimulation of stellate, T2 and T3 ganglia, and after randomized electrocautery of T2 and T3 ganglia in 20 patients. We analyzed the statistics according to paired t-test with Bonferroni adjustment. We found that palm skin temperature decreases significantly after stellate stimulation. While rising significantly after destruction of T2 ganglion in the presence of intact T3 ganglion (P = 0.00001), palm skin temperature did not rise significantly after T3 destruction in the presence of intact T2 (P = 0.779). Following T2 and T3 destruction, however, palm skin temperature rose despite stellate stimulation. This suggests that T2 ganglion determines palm skin temperature while stellate and other upper thoracic ganglia may play a minor role, that T2 sympathectomy suffices for the treatment of essential palmar hyperhidrosis, and that sympathectomy for Raynaud's disease might skip stellectomy.

Adolescent↗
PubMed1997

SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor alpha (RARalpha) and PLZF-RARalpha oncoproteins associated with acute promyelocytic leukemia.

Retinoic acid receptors (RARs) are hormone-regulated transcription factors that control key aspects of normal differentiation. Aberrant RAR activity may be a causal factor in neoplasia. Human acute promyelocytic leukemia, for example, is tightly linked to chromosomal translocations that fuse novel amino acid sequences (denoted PML, PLZF, and NPM) to the DNA-binding and hormone-binding domains of RARalpha. The resulting chimeric receptors have unique transcriptional properties that may contribute to leukemogenesis. Normal RARs repress gene transcription by associating with ancillary factors denoted corepressors (also referred to as SMRT, N-CoR, TRAC, or RIP13). We report here that the PML-RARalpha and PLZF-RARalpha oncoproteins retain the ability of RARalpha to associate with corepressors, and that this corepressor association correlates with certain aspects of the leukemic phenotype. Unexpectedly, the PLZF moiety itself can interact with SMRT corepressor. This interaction with corepressor is mediated, in part, by a POZ motif within PLZF. Given the presence of POZ motifs in a number of known transcriptional repressors, similar interactions with SMRT may play a role in transcriptional silencing by a variety of both receptor and nonreceptor transcription factors.

DNA-Binding Proteins↗
PubMed1997

Plasticity of tetramer formation by retinoid X receptors. An alternative paradigm for DNA recognition.

Retinoid X receptors (RXRs) are transcription factors that traditionally have been thought to bind DNA as protein dimers. Recently, however, it has been recognized that RXRs can also bind to DNA as protein tetramers. Receptor tetramers form cooperatively on response elements containing suitably reiterated half-sites, and play an important role in determining the specificity of DNA recognition by different nuclear receptors. We report here that RXR tetramers exhibit significant functional plasticity, and form on response elements possessing diverse half-site orientations and spacings. This ability of RXRs to form tetramers and related oligomers appears to contribute to the synergistic transcriptional activation observed when multiple, spatially separated response elements are introduced into a single promoter. Oligomerization may therefore be a common paradigm for DNA recognition and combinatorial regulation by several different classes of transcription factors.

Animals↗