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Biomedical subjects

C W Wong

Publications and source records attributed to C W Wong.

At least 19 recordsLinked to original sources

Immunosuppressive effects of Marek's disease virus (MDV) and herpesvirus of turkeys (HVT) in broiler chickens and the protective effect of HVT vaccination against MDV challenge.

Much of the impact of Marek's disease in broiler chickens is considered to be due to immunosuppression induced by Marek's disease virus (MDV). The present study evaluates the effects of an Australian isolate of pathogenic MDV (strain MPF 57) and a non-pathogenic vaccinal strain of herpesvirus of turkeys (HVT) (strain FC 126) on the immune system of commercial broiler chickens for 35 days following challenge at days 0 or 3 of age. It also investigates the extent of protection provided by HVT vaccine against MDV-induced immunosuppression. Immune system variables, including relative lymphoid organ weight, blood lymphocyte phenotype (CD45+/CD3+, putatively T, and CD45+/LC+, putatively B) and antibody production following vaccination against infectious bronchitis (IB) at hatch, were used to assess the immune status of chickens. Immunosuppression was also assessed by susceptibility to secondary challenge with pathogenic Escherichia coli on day 29 post-MDV challenge. MDV infection reduced the weight of the thymus and bursa of Fabricius, the numbers of circulating T lymphocytes and B lymphocytes, and IB antibody titre. The timing of these effects varied. MDV infection greatly increased susceptibility to E. coli infection. HVT alone caused mild depletion of T and B lymphocytes but no effect on immune organ weight or IB titre. Vaccination with HVT provided good protection against most of the immunosuppressive effects of MDV but not against MDV-induced growth impairment and reduced responsiveness to IB vaccination, suggesting that recent Australian strains of MDV may be evolving in virulence to overcome the protective effects of HVT.

Animals↗

Structure-function evaluation of ER alpha and beta interplay with SRC family coactivators. ER selective ligands.

Analysis of estrogen receptor alpha and beta interplay with other transcription factors is critical to the understanding of how small molecules, the cognate ligands for these receptors, selectively regulate the mode and amplitude of gene transcription by affecting receptor activity. To better understand the molecular mechanisms of selective action of estrogen receptor ligands, we characterized estrogen receptor alpha and beta (ER) interaction with the p160 family of coactivators. We also investigated how these interactions are affected by binding of specific ligands. We show that ER alpha and beta utilize different LXXLL motifs for their interaction with p160 family members. We found that significant differences exist between the affinity of the nuclear receptor interacting domain (NRID) and interaction of separate LXXLL motifs with ERs. This result indicates that a single LXXLL motif is unlikely to be sufficient for interaction with receptors, and that regions other than LXXLL motifs also participate in ER-p160 complex formation. We found that ER alpha and beta have strong affinity preferences for particular coactivators. These results suggest that ER-mediated transcription is not driven by a random mixture of ER-coactivator complexes. We also show that some ER ligands are functionally specific. We describe a ligand that binds to both receptors, but enhances only ER beta interaction with SRC1 and SRC3 while exhibiting little effect on the ER alpha interaction with these proteins. Finally, we provide data that suggest how genistein may selectively recruit coactivators when liganded to ERs. It enhances the interaction of ERs with SRC1 and SRC3, but demonstrates a minimal effect on receptor interaction with DRIP205 and CBP.

Acetyltransferases↗

Apoptosis: an early event in metastatic inefficiency.

Whereas large numbers of cells from a primary tumor may gain access to the circulation, few of them will give rise to metastases. The mechanism of elimination of these tumor cells, often termed "metastatic inefficiency," is poorly understood. In this study, we show that apoptosis in the lungs within 1-2 days of introduction of the cells is an important component of metastatic inefficiency. First, we show that death of transformed, metastatic rat embryo cells occurred via apoptosis in the lungs 24-48 h after injection into the circulation. Second, we show that Bcl-2 overexpression in these cells inhibited apoptosis in culture and also conferred resistance to apoptosis in vivo in the lungs 24-48 h after injection. This inhibition of apoptosis led to significantly more macroscopic metastases. Third, comparison between the extent of apoptosis by a poorly metastatic cell line to that by a highly metastatic cell line 24 h after injection in the lungs revealed more apoptosis by the poorly metastatic cell line. These results indicate that apoptosis, which occurs at 24-48 h after hematogenous dissemination in the lungs is an important determinant of metastatic inefficiency. Although prior work has shown an association between apoptosis in culture and metastasis in vivo, this work shows that apoptosis in vivo corresponds to decreased metastasis in vivo.

Animals↗

Effects of dietary protein types on immune responses and levels of infection with Eimeria vermiformis in mice.

The present study reports the dietary effects of bovine alpha whey fraction, bovine casein and soy protein isolate on the immune responsiveness of C57BL/6J mice infected with Eimeria vermiformis. During the patent period, mice fed alpha whey fraction had significantly higher blood total white cell, CD4+ and CD8+ lymphocyte counts and higher Con A-stimulated IFN-gamma production by spleen cells than those fed other protein sources, but there was no significant difference in output of faecal oocysts. Casein-fed mice had significantly higher levels of Con A- stimulated IFN-gamma production and a lower output of faecal oocysts than soy-fed mice. The study demonstrated that dietary proteins have different impacts on immune responsiveness and level of parasitic infection in the gut; however, the mechanisms affecting level of infection are not clear. These effects appeared not to be solely related to nutritional properties of the diets. Further research into the underlying immune mechanisms and possible direct interactions between bioactive proteins and the parasite E. vermiformis should be fruitful.

Animals↗

Functional interactions between the estrogen receptor and DRIP205, a subunit of the heteromeric DRIP coactivator complex.

Nuclear receptors regulate transcription in direct response to their cognate hormonal ligands. Ligand binding leads to the dissociation of corepressors and the recruitment of coactivators. Many of these factors, acting in large complexes, have emerged as potential chromatin remodelers through intrinsic histone modifying activities. In addition, other ligand-recruited complexes appear to act more directly on the transcriptional apparatus. The DRIP complex is a 15-subunit complex required for nuclear receptor transcriptional activation in vitro. It is recruited to the receptor in response to ligand through specific interactions of one subunit, DRIP205. We present evidence that DRIP205 interacts with another member of the steroid receptor subfamily, estrogen receptor (ER). This interaction occurs in an agonist-stimulated fashion which in turn is inhibited by several ER antagonists. In vivo, a fragment of DRIP205 containing only its receptor interacting region acts to selectively inhibit ER's ability to activate transcription in response to estradiol. These observations suggest a key role for the DRIP coactivator complex in estrogen-ER signaling.

Animals↗

Biosynthetic studies on the tropane ring system of the tropane alkaloids from Datura stramonium.

Isotopic labelling experiments have been carried out in Datura stramonium root cultures with the following isotopically labelled precursors; [2H3]- [2-13C, 2H3]-, [1-13C, 18O2]-acetates, 2H2O, [2H3-methyl]-methionine, [2-13C]-phenyllactate, [3-2H]-tropine and [2'-13C, 3-2H]-littorine. The study explored the incorporation of isotope into the tropane ring system of littorine 1 and hyoscyamine 2 and revealed that deuterium from acetate is incorporated only into C-6 and C-7, and not into C-2 and C-4 as previously reported. Oxygen-18 was not retained at a detectable level into the C(3)-O bond from [1-13C, 18O2]-acetate. The intramolecular nature of the rearrangement of littorine 1 to hyoscyamine 2 is revealed again by a labelling study using [2'-13C, 3-2H]-littorine, [2-13C]-phenyllactate and [3-2H]-tropine.

Alkaloids↗

Corpus callosum and cerebral laterality in a modular brain model.

This paper elaborates the function of corpus callosum in the brain model that contains encoding and modulating axons: the former encode data as presynaptic axonal 'on-off' patterns, and the latter help the former convert data into long-term memory through the development of long-term potentiation and depression. It is hypothesized that callosal axons transfer data codes as interhemispheric memory. Bisection of corpus callosum cuts off interhemispheric data transfer and results in strange-hand syndrome, decreased attention and difficulties in acquiring new interdependent bimanual skills. While uniting two hemispheres for a unitary consciousness, corpus callosum contributes to two similar sets of integrated abstract memory, one in each hemisphere. Therefore, it takes bilateral cerebral lesions to manifest a failure of converting short-term memory into long-term memory. The asymmetric callosal data transfer may correlate with cerebral laterality where a cerebral function, such as language, is conducted mainly in one hemisphere for the benefit of less interhemispheric data-traffic. Complete lateralization of a cerebral function is the rare occasion when the specialized neuron groups (modules) for that function all reside in one hemisphere. It is possible that many cerebral functions including language are incompletely lateralized, and corpus callosum links the non-lateralized modules with the lateralized ones. The more the cerebral lateralization, the fewer the non-lateralized modules to be linked, and the smaller the corpus callosum.

Corpus Callosum↗

Expression of one group of genes maintains one unit of long-term memory in a brain model.

In a brain model, a unit of long-term memory is stored in the encoding synapses of a neuron as a presynaptic axonal 'on-off' pattern through the establishment of long-term potentiation (LTP) and long-term depression (LTD). Repetitive activation of one presynaptic axonal 'on-off' pattern speeds up the subsequent re-activation of the same pattern by inducing expression of a corresponding group of genes in support of the enzymes, protein substrates, and second messengers for the LTP and LTD that encode the unit of long-term memory. Phantom limb pains are memorized and re-activated through the expression of the corresponding group of genes, and re-experiencing the stressful event in post traumatic stress syndrome results from the expression of another group of genes. The sense of requiring less time to experience the content of a successfully retrieved long-term memory reflects an increased speed of re-activating the presynaptic axonal 'on-off' patterns of the memory, or an increased speed of thinking. Giving rise to a sense of familiarity with new things, déjà vu may also be a mental state with increased speed of thinking. The speed of thinking may be decreased in jamais vu that is opposite to déjà vu. Progressive increases in the speed of thinking when engaging in a hobby may open up a previously unused neural pathway that turns a previously happy feeling into an aversive one.

Gene Expression↗

Rapid-eye-movement sleep involves the memory-conversion circuits in a brain model.

People can remember the content of a dream in rapid eye movement (REM) sleep but cannot do so in slow-wave sleep. According to a brain model, memory is stored in encoding synapses as presynaptic axonal 'on-off' patterns and modulating synapses help encoding synapses convert short-term memory into long-term memory. These lead to the hypothesis that REM sleep involves modulating synapses of the memory-conversion circuits including the anterior nuclei and dorsomedial nuclei of the thalamus. Cortical neurons get more rest in slow-wave sleep than in REM sleep. The locus coeruleus, raphe nuclei, and tuberomammillary nuclei get more rest during REM sleep when these nuclei cease to fire. The paralyses of peripheral muscles during REM sleep and cataplexy, and cessation of chorea, athetosis, hemiballismus, and parkinsonism tremor during sleep may result from spinal cord inhibition by the gigantocellular nuclei and raphe nuclei at the reticular formation. Sleep and wake relate to the light-dark cycle on the Earth. Were the light-dark cycle 50 hours a day, the human circadian clock might be around 50 hours. With increasing use of artificial light to keep people awake at night, it may affect the circadian rhythm and firing rate of neurons, the presynaptic axonal 'on-off' patterns as content of consciousness, and the mood.

Brain↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗