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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
PubMed2006

Involvement of phenobarbital and SKF 525A in the hepatotoxicity of antifungal drugs itraconazole and fluconazole in rats.

Itraconazole and fluconazole are potent wide spectrum antifungal drugs. Both of these drugs induce hepatotoxicity clinically. The mechanism underlying the hepatotoxicity is unknown. The purpose of this study was to investigate the role of phenobarbital (PB), an inducer of cytochrome P450 (CYP), and SKF 525A, an inhibitor of CYP, in the mechanism of hepatotoxicity induced by these two drugs in vivo. Rats were pretreated with PB (75 mg/kg for 4 days) prior to itraconazole or fluconazole dosing (20 and 200 mg/kg for 4 days). In the inhibition study, for 4 consecutive days, rats were pretreated with SKF 525A (50 mg/kg) or saline followed by itraconazole or fluconazole (20 and 200 mg/kg) Dose-dependent increases in plasma alanine aminotransferase (ALT), gamma-glutamyl transferase (gamma-GT), and alkaline phosphatase (ALP) activities and in liver weight were detected in rats receiving itraconazole treatment. Interestingly, pretreatment with PB prior to itraconazole reduced the ALT and gamma-GT activities and the liver weight of rats. No changes were observed in rats treated with fluconazole. Pretreatment with SKF 525A induced more severe hepatotoxicity for both itraconazole and fluconazole. CYP 3A activity was inhibited dose-dependently by itraconazole treatment. Itraconazole had no effects on the activity of CYP 1A and 2E. Fluconazole potently inhibited all three isoenzymes of CYP. PB plays a role in hepatoprotection to itraconazole-induced but not fluconazole-induced hepatotoxicity. SKF 525A enhanced the hepatotoxicity of both antifungal drugs in vivo. Therefore, it can be concluded that inhibition of CYP may play a key role in the mechanism of hepatotoxicity induced by itraconazole and fluconazole.

Animals↗
PubMed2006

Long-term effects of early-life dietary L-carnitine on lymphoid organs and immune responses in Leghorn-type chickens.

The long-term effects of supplementing Leghorn-type chickens with dietary L-carnitine after hatching for 4 weeks on growth, lymphoid organ weights, humoral and cell-mediated immune responses were assessed in a 12-week study. A commercial starter feed supplemented with 0 (control), 100 (LC) or 1,000 (HC) mg L-carnitine/kg was offered to day-old ISA Brown cockerels for 4 weeks, then all birds were given a commercial pullet grower feed for another 8 weeks. No differences (p > 0.05) in growth rates, feed intake or feed utilisation efficiency existed among the dietary treatments throughout the study. Compared with control birds, HC-fed birds had a lower (p < 0.05) thymus weight relative to bodyweight (BW) at Week 4, but a higher (p < 0.05) relative thymus weight at Week 12. A higher (p < 0.05) serum primary antibody response to sheep red blood cells (SRBC) in HC-fed birds than in the other two groups was also detected at Week 12. Relative spleen or bursa weights and cutaneous responses of toe webs to phytohaemagglutimin (PHA) (an in vivo indicator of cell-mediated immune responses) did not differ (p > 0.05) among dietary treatments at any time. It is concluded that a short-term supply of dietary L-carnitine to a conventional commercial feed after hatching enhanced subsequent humoral immunity in Leghorn-type chickens. Further study is warranted to confirm such a long-term effect.

Animal Feed↗
PubMed2006

Use of avian influenza vaccination in Hong Kong.

Outbreaks of H5N1 highly pathogenic avian influenza (HPAI) that occurred in Hong Kong up until February/March 2002 were controlled by stamping out. With endemic presence of the virus in the region and large daily importation of poultry to Hong Kong, the Administration considered that further risk management measures, in addition to improved biosecurity and enhanced surveillance, were necessary to prevent outbreaks. Vaccination using a killed H5N2 vaccine was evaluated over a 12-month period in the district with the last HPAI cases in the early 2002 outbreak. The vaccination trial showed that farmer-administered killed H5N2 vaccine produced suitable flock antibody responses; vaccinated birds were protected against H5N1 HPAI virus challenge and excreted significantly less H5N1 virus; and vaccination was able to control virus excretion in flocks during field outbreaks. Universal vaccination of local chicken farms was introduced in June 2003 and by the end of 2003 all chickens entering the live poultry markets in Hong Kong were vaccinated by killed H5N2 vaccine. In addition to vaccination, an enhanced biosecurity programme on farms and in live poultry markets and a comprehensive surveillance programme in poultry, wild birds, recreation park birds and pet birds were in place. Vaccination use and performance is closely monitored. This programme was successful in protecting local farms and live poultry markets from H5N1 outbreaks during the regional H5N1 outbreaks in 2004.

Animals↗
PubMed2005

Long-term effects of early life L-arginine supplementation on growth performance, lymphoid organs and immune responses in Leghorn-type chickens.

The effects of a short-term dietary arginine supplementation after hatching on subsequent growth and the immune system were assessed in growing male Leghorn-type chickens. An arginine-deficient basal diet (67 g/kg) supplemented with 0 (control), 2.7 (LA) or 5.4 (HA) g L-arginine/kg, was offered ad libitum to 1-d-old male ISA Brown chicks for 4 weeks, then all birds were offered ad libitum a commercial pullet grower feed (8.9 g arginine/kg) for another 8 weeks. Supplemented birds had higher growth rates and feed intake than control birds during the 4-week supplementation period, but these effects did not persist into the subsequent periods. When the supplementation ceased at week 4, no differences in lymphoid organ weights relative to body weight (BW), primary serum antibody levels against sheep red blood cells (SRBC) or cutaneous reactivity of toe webs to phytohaemagglutinin (PHA) were detected. LA-fed birds had lower immunoglobulin (Ig) G levels against bovine serum albumin (BSA) than the control at week 4, but this effect did not persist at weeks 8 and 12. No difference in anti-BSA IgM levels was detected among birds at week 4; at week 12, however, the LA-fed birds had a significantly higher anti-BSA IgM level than the control. An increased anti-SRBC antibody level and a reduced relative bursa weight in HA-fed birds were evident at week 8, without any prior effects. It is concluded that short-term supplementary L-arginine had minimal effects on immunity, but some enhancement of SRBC antibody responses in later stages of growth was observed with previous L-arginine administration.

Aging↗
PubMed2005

Carry-over effects of dietary yeast RNA as a source of nucleotides on lymphoid organs and immune responses in Leghorn-type chickens.

1. The carry-over effects of supplementing Leghorn-type chickens with yeast RNA as a dietary source of nucleotides for 4 weeks on growth, lymphoid organ weights and immune responses were assessed in a 12-week study. 2. A commercial starter feed supplemented with 0 (control), 5 (LR) or 10 (HR) g yeast RNA/kg was offered to 1-d-old male ISA Brown chicks for 4 weeks, and then all birds were given a commercial pullet grower feed for another 8 weeks. Growth performance, antibody responses to sheep red blood cells (SRBC) and cutaneous reactivity of toe webs to phytohaemagglutinin (PHA)-M were measured at 4-week intervals. 3. Growth rates, feed intake and feed efficiency were not affected by dietary yeast RNA during the supplementary period, but birds previously offered the HR diet grew faster than control birds during weeks 4 to 8.4. LR-fed birds had a higher spleen weight relative to body weight (BW) than control birds at week 4, but this effect was not detected at other times. 5. Serum primary antibody levels against SRBC were not affected by dietary yeast RNA at any time. 6. The toe-web PHA response was significantly higher at week 8 in control birds than in birds previously given the LR diet, although no difference among dietary treatments was observed at other times. 7. It is concluded that the addition of yeast RNA as a source of nucleotides to a commercial diet selectively stimulated the development of the spleen in young birds, but this effect did not persist into a later stage of the bird's life.

Animal Feed↗
PubMed2005

BRAF and NRAS mutations are uncommon in melanomas arising in diverse internal organs.

BACKGROUND: Malignant melanoma arising from different body compartments may be associated with differing aetiological factors and clinical behaviour, and may manifest diverse molecular genetic profiles. Although many studies have focused on cutaneous melanoma, little is known of mucosal and other types of melanoma. In particular, malignant melanoma of soft parts is different from other melanomas in many respects, yet manifests a common melanocytic differentiation. Mutation of BRAF is now known to be common in cutaneous melanomas, and raises possible new therapeutic options of anti-RAF treatment for these patients. Few data are available for non-cutaneous melanomas. AIMS: To study the incidence of BRAF and NRAS mutations in melanomas arising in diverse internal organs. METHODS: Fifty one melanomas from various internal organs were investigated for BRAF and NRAS mutation by direct DNA sequencing. RESULTS: BRAF and NRAS mutations were found in two and five mucosal melanomas arising from the aerodigestive and female genital tracts (n = 36). Their occurrence is mutually exclusive, giving a combined mutation incidence rate of 19.4% in mucosal melanomas. Both BRAF and NRAS mutations were absent in malignant melanoma of soft parts (n = 7). BRAF mutation was also absent in uveal melanoma (n = 6), but was seen in two of five cutaneous melanomas. The incidence of BRAF or combined BRAF/NRAS mutations in all non-cutaneous groups was significantly lower than published rates for cutaneous melanomas. CONCLUSION: Each melanoma subtype may have a unique oncogenetic pathway of tumour development, and only a small fraction of non-cutaneous melanomas may benefit from anti-RAF treatment.

Adolescent↗
PubMed2005

Dynamic traction and passive mobilization for the rehabilitation of zone II flexor tendon injuries: a modified regime.

This retrospective study aims to evaluate the effectiveness of the modified regime for rehabilitation of Zone II flexor tendon injuries in Sibu Hospital. From January to December 2003, 8 patients with 15 injured digits were treated by using the combined method of dynamic traction and passive mobilization. According to Strickland's criteria, 14 (93.3%) digits achieved good to excellent outcomes and only 1 (6.7%) was rated as poor. No occurrence of tendon rupture was noted. The overall grip strength of the injured hand was 50.1% of the uninjured hand at 3 months after the repair. Our results compare favorably with the other published studies. We believed that this modified regime is as effective as other established regimes and suitable to be adopted in our setting. Further study with larger sample group will be required to consolidate our findings.

Adult↗
PubMed2004

Psychological distress and negative appraisals in survivors of severe acute respiratory syndrome (SARS).

BACKGROUND: Severe acute respiratory syndrome (SARS) is a novel disease. The authors have limited knowledge of its impact on mental health. The present study aimed to examine the level and extent of psychological distress of SARS survivors following 1-month recovery, to explore patients' negative appraisals of the impact of SARS, and to evaluate the associations between psychological distress and negative appraisals. METHOD: The Beck Anxiety Inventory, the Beck Depression Inventory, and a newly developed measure, the SARS Impact Scale (SIS), were mailed to 453 Hong Kong Chinese SARS survivors discharged from hospital for 4 weeks or more. RESULTS: A total of 425 patients received the questionnaires and 180 (mean age 36.9 years; 120 women) gave valid replies. The response rate was 42.4 %. The participants also represented 13.6 % of all adult survivors in Hong Kong. About 35 % of respondents reported 'moderate to severe' or 'severe' ranges of anxiety and/or depressive symptoms. It was found that those working as healthcare workers or having family members killed by SARS were more prone to develop subsequent high levels of distress. Factor analyses extracted three meaningful factors of the SIS, namely 'survival threat', 'physical impact', and 'social impact'. Negative appraisals at the acute phase and 1-month recovery significantly accounted for substantial portions of variances for anxiety and depressive symptoms, after the effects of other psychosocial variables were controlled. CONCLUSIONS: Psychological distress of SARS survivors at 1-month recovery is real and significant. Negative appraisals may play a pivotal role in the development of psychological distress for SARS survivors, at least in the short term.

Adaptation, Psychological↗
PubMed2002

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗