Prevalence of antibody to human T cell leukaemia/lymphoma virus in women attending antenatal clinic in southeast London: retrospective study.
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Female↗
Biomedical subjects
T Leung
Publications and source records attributed to T Leung.
A validity study of Ullanlinna Narcolepsy Scale in Hong Kong Chinese.
OBJECTIVE: To validate the Chinese version of Ullanlinna Narcolepsy Scale (CUNS). METHODS: A total of 234 subjects [163 male (69.7%) and 71 female (30.3%)] including 17 patients with narcolepsy, 21 normal controls and 196 patients with various sleep and psychiatric disorders were studied. The diagnoses of these patients were independently ascertained with sleep laboratory confirmation whenever indicated. All the subjects were interviewed through the telephone by a trained lay interviewer who was blind to the diagnosis. The questionnaire included demographic information, sleep habits and CUNS. RESULTS: Narcoleptic patients had a significantly higher CUNS score (18.6+/-4.7; 95% confidence interval (CI) 16.2-21.0) and differentiated well from all the other groups (F(6,227)=28.4, P<0.001). The CUNS has a satisfactory internal consistency with Cronbach's alpha of 0.75. The principal component analysis with varimax rotation revealed two factors, namely sleepiness and cataplexy factors, which accounted for 45.5% of the total variance. The best cut-off point for the CUNS scale was found to be at 13/14 with high specificity (93.5%), sensitivity (94.1%), negative predictive value (NPV, 99.5%) and modest positive predictive value (PPV, 53.3%). The AUC of receiver operating characteristic (ROC) analysis was 0.97 (95% CI 0.95-0.99). CONCLUSIONS: The CUNS was validated with satisfactory psychometric properties. The cross-cultural validation of UNS scale suggested that it could be used across the ethnic groups.
Adolescent↗
Phosphorylation of ERM proteins at filopodia induced by Cdc42.
BACKGROUND: ERM (ezrin, radixin, and moesin) proteins function as membrane-cytoskeletal linkers, and are known to be localized at filopodia and microvilli-like structures. We have shown that Rho-associated kinase (Rho-kinase)/ROKalpha/ROCK II phosphorylates moesin at Thr-558 at the lower stream of Rho, and the phosphorylation is crucial to the formation of microvilli-like structures (Oshiro, N., Fukata, Y. & Kaibuchi, K. (1998) Phosphorylation of moesin by Rho-associated kinase (Rho-kinase) plays a crucial role in the formation of microvilli-like structures. J. Biol. Chem. 273, 34663- 34666). However, the role of ERM proteins in the formation of filopodia is less well characterized. RESULTS: Here we examined the phosphorylation state of ERM during filopodia formation induced by Cdc42 using the antibody recognizing ERM proteins phosphorylated at COOH (C)-terminal threonine. When NIH 3T3 cells were transfected with constitutively active Cdc42 (Cdc42V12), filopodia formation was induced and phosphorylation of ERM at C-terminal threonine was observed at the tip of filopodia, while the phosphorylation levels of ERM were lower and phosphorylated ERM was distributed throughout the cytoplasm in the control cells. We also showed that Myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK) which has been identified as an effector of Cdc42, phosphorylated moesin at C-terminal threonine in a cell-free system. Coexpression of the dominant negative form of MRCK inhibited both the formation of filopodia and accumulation of C-terminal threonine-phosphorylated ERM proteins at filopodia induced by Cdc42V12. CONCLUSION: The formation of filopodia induced by Cdc42 is accompanied by phosphorylation of ERM proteins, and MRCK is a candidate for the kinase that phosphorylates ERM proteins at filopodia.
3T3 Cells↗
Regulation of meristem organization and cell division by TSO1, an Arabidopsis gene with cysteine-rich repeats.
In higher plants, meristem organization and cell division regulation are two fundamentally important and intimately related biological processes. Identifying and isolating regulatory genes in these processes is essential for understanding higher plant growth and development. We describe the molecular isolation and analyses of an Arabidopsis gene, TSO1, which regulates both of these processes. We previously showed that tso1 mutants displayed defects in cell division of floral meristem cells including partially formed cell walls, increased DNA content, and multinucleated cells (Liu, Z., Running, M. P. and Meyerowitz, E. M. (1997). Development 124, 665-672). Here, we characterize a second defect of tso1 in influorescence meristem development and show that the enlarged influorescence in tso1 mutants results from repeated division of one inflorescence meristem into two or more influorescence meristems. Using a map-based approach, we isolated the TSO1 gene and found that TSO1 encodes a protein with cysteine-rich repeats bearing similarity to Drosophila Enhancer of zeste and its plant homologs. In situ TSO1 mRNA expression pattern and the nuclear localization of TSO1-GFP are consistent with a regulatory role of TSO1 in floral meristem cell division and in influorescence meristem organization.
Amino Acid Sequence↗
Control of jaw closing forces: a comparison between natural tooth and osseointegrated implant.
The aim of this in vivo study was to compare the precision of control of jaw closing forces through implants versus natural teeth. Ten partially dentate subjects with fixed implant prostheses in their mandibles took part in the study. A force transducer was used to assess the ability of the subjects to follow pre-determined jaw closing cycles. The error in tracking the target increased as the force increased for both implant and tooth sites. Within the range of forces tested, there was no significant difference in the error between the implant and natural tooth sites.
Bite Force↗
Control of jaw closing forces: a comparison between implant-stabilised overdenture wearers and complete denture wearers.
This study compared the precision of control of jaw closing forces in two groups of edentulous subjects: ten patients wearing implant-stabilised mandibular overdentures and ten complete denture wearers who were satisfied with their prostheses. A force transducer was used to assess the ability of the subjects to follow pre-determined jaw closing cycles. The error in tracking the target increased as the force increased for both the implant and denture group. In this experiment, the overdenture wearers were less able to control jaw closing forces than successful wearers of conventional complete dentures.
Aged↗
Sleep problems in Chinese elderly in Hong Kong.
BACKGROUND: To examine the sleep habits and one-year prevalence of sleep disturbance (difficulty in falling asleep, broken sleep and early morning wakening) as well as insomnia (subjectively inadequate or poor sleep) in an elderly Chinese population in Hong Kong. METHOD: In Phase 1, a representative sample of elderly aged 70 years or above were interviewed with a sleep questionnaire, and Cantonese versions of the Mini-Mental State Examination (CMMSE) and Geriatric Depression Scale(CGDS). In Phase 2, those with scores suggestive of cognitive impairment on CMMSE or depression on CGDS were interviewed by psychiatrists for making clinical diagnoses according to DSM IV. RESULTS: 1,034 elderly were interviewed in Phase 1. Occasional or persistent sleep disturbance were reported by 75% and insomnia in 38.2% of elderly. Slightly less than half of elderly with sleep disturbance complained of insomnia. Advancing age was associated with a higher rate of sleep disturbance while females had a higher rate of insomnia. Factors associated with sleep disturbance and insomnia included poor perceived health, past history of smoking, current depressive disorders, more chronic physical illness, more life events and more somatic complaints. Only 2.8% of the sample had taken sleeping pills within a one-year period. CONCLUSIONS: Sleep disturbance and insomnia are two separate but overlapping constructs and should be differentiated. Sleep disturbance is very common in the elderly and may be due to physiological changes with ageing. In contrast, those with a concommitant complaint of insomnia have impaired physical and mental health and may merit more medical attention.
Aged↗
The myotonic dystrophy kinase-related Cdc42-binding kinase is involved in the regulation of neurite outgrowth in PC12 cells.
The myotonic dystrophy kinase-related Cdc42-binding kinase (MRCKalpha) has been implicated in the morphological activities of Cdc42 in nonneural cells. Both MRCKalpha and the kinase-related Rho-binding kinase (ROKalpha) are involved in nonmuscle myosin light-chain phosphorylation and associated actin cytoskeleton reorganization. We now show that in PC12 cells, overexpression of the kinase domain of MRCKalpha and ROKalpha resulted in retraction of neurites formed on nerve growth factor (NGF) treatment, as observed with RhoA. However, introduction of kinase-dead MRCKalpha did not result in NGF-independent neurite outgrowth as observed with dominant negative kinase-dead ROKalpha or the Rho inhibitor C3. Neurite outgrowth induced by NGF or kinase-dead ROKalpha was inhibited by dominant negative Cdc42(N17), Rac1(N17), and the Src homology 3 domain of c-Crk, indicating the participation of common downstream components. Neurite outgrowth induced by either agent was blocked by kinase-dead MRCKalpha lacking the p21-binding domain or by a minimal C-terminal regulatory region consisting of the cysteine-rich domain/pleckstrin homology domain plus a region with homology to citron. The latter region alone was an effective blocker of NGF-induced outgrowth. These results suggest that although ROKalpha is involved in neurite retraction promoted by RhoA, the related MRCKalpha is conversely involved in neurite outgrowth promoted by Cdc42 and Rac.
Amino Acid Sequence↗
Association between CYP2A6 and CYP2C19 mutant alleles.
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Alleles↗
Child sexual abuse in Hong Kong: double victimization?
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Adolescent↗
Bone marrow transplantation for chronic granulomatous disease: long-term follow-up and review of literature.
Chronic granulomatous disease (CGD) is a heterogeneous group of disorders with defective respiratory burst activity in phagocytes which results in recurrent pyogenic infections. We report an 8-year-old boy with X-linked CGD who received an HLA-identical BMT from his sister. The nitroblue tetrazolium test returned to normal 3 months post transplant. Neutrophil engraftment has been stable for 7 years post BMT. Our patient was the eighth case of CGD successfully treated by BMT. Conditioning regimens in these patients have consisted mainly of BU and CY. We suggest that BMT is a safe and effective method of cure for patients with CGD. BMT should be considered for patients with HLA-identical siblings.
Bone Marrow Transplantation↗
Sleep paralysis in the elderly.
Isolated sleep paralysis (SP) is a common sleep phenomenon that is highly colored by indigenous beliefs. In Hong Kong Chinese, the 'ghost oppression phenomenon' (GO) has been shown to be descriptively identical to SP. The prevailing concept is that the majority of cases with SP have their onset during adolescence, but the lack of any systematic study on an older population means that late-onset cases can not be excluded. In a study investigating the prevalence of mental disorders in Chinese elderly aged above 70 y in Hong Kong, we employed the revised GO questionnaire to study the prevalence of SP in this group of elderly as well. One hundred and fifty-eight subjects were finally analyzed for the study. Almost 18% (95% C.I. 11.77%, 23.68%) of the subjects reported experiences of GO. Their description of the features of GO showed striking similarity to those of SP. There was a clear bimodal distribution of onset of GO with peaks during adolescence and after age 60 y. At least one-third of the cases were late onset. In concordance with the rapid eye movement (REM)/wakefulness dissociation hypothesis of SP, those elderly with GO+ experiences also had more frequent nocturnal sleep disturbances. A family history was reported in 10% of subjects.
Age of Onset↗
Gradual withdrawal of long-term anticholinergic antiparkinson medication in Chinese patients with chronic schizophrenia.
Previous antiparkinson drug withdrawal studies involving white subjects have yielded inconclusive findings, whereas there is a paucity of data concerning Asian patients. A double-blind, placebo-controlled, randomized trial using gradual withdrawal of antiparkinson medication was conducted to evaluate the need for maintenance antiparkinson therapy for clinically stable Chinese patients with chronic schizophrenia. Seventy-five schizophrenic subjects who had received a diagnosis according to DSM-IV who had been ill for at least 5 years and on antipsychotic and antiparkinson medication for a minimum of 2 years entered the study. After baseline assessment, 58 subjects were matched according to age, sex, age at onset, length of illness, dose and length of antipsychotic and antiparkinson medication, and the presence of various extrapyramidal side effects. Randomly assigned dose-reduction and control groups were formed consisting of 29 subjects each. Trihexyphenidyl (THP), the only oral antiparkinson drug used in the study, was reduced by 1 mg every 2 weeks, whereas other psychotropic medication remained unchanged. Monthly assessment was performed using the Brief Psychiatric Rating Scale, Hamilton Rating Scale for Depression, Abnormal Involuntary Movement Scale, Simpson-Angus Scale, Barnes Akathisia Rating Scale, and the Nursing Observation Scale for Inpatient Evaluation-30. Complete withdrawal of THP was possible in 25 (90%) of the 28 subjects who completed the study, whereas considerable dose reduction was achieved in the remaining 3 subjects. There were no significant differences between dose reduction and control groups on any of the rating scales at the completion of the study. Our results suggest that long-term prophylactic administration of antiparkinson medication is unnecessary in the treatment of the majority of Chinese patients with chronic schizophrenia because withdrawal was accomplished without adverse mental or motor effects.
Adult↗
The zebrafish bozozok locus encodes Dharma, a homeodomain protein essential for induction of gastrula organizer and dorsoanterior embryonic structures.
The dorsal gastrula organizer plays a fundamental role in establishment of the vertebrate axis. We demonstrate that the zebrafish bozozok (boz) locus is required at the blastula stages for formation of the embryonic shield, the equivalent of the gastrula organizer and expression of multiple organizer-specific genes. Furthermore, boz is essential for specification of dorsoanterior embryonic structures, including notochord, prechordal mesendoderm, floor plate and forebrain. We report that boz mutations disrupt the homeobox gene dharma. Overexpression of boz in the extraembryonic yolk syncytial layer of boz mutant embryos is sufficient for normal development of the overlying blastoderm, revealing an involvement of extraembryonic structures in anterior patterning in fish similarly to murine embryos. Epistatic analyses indicate that boz acts downstream of beta-catenin and upstream to TGF-beta signaling or in a parallel pathway. These studies provide genetic evidence for an essential function of a homeodomain protein in beta-catenin-mediated induction of the dorsal gastrula organizer and place boz at the top of a hierarchy of zygotic genes specifying the dorsal midline of a vertebrate embryo.
Animals↗
Hematogenous dissemination of hepatocytes and tumor cells after surgical resection of hepatocellular carcinoma: a quantitative analysis.
The only hope of long-term survival for patients with hepatocellular carcinoma (HCC) is surgical resection or liver transplantation. However, recurrence or metastasis formation is common after surgery. We aim to assess whether surgical resection leads to hematogenous dissemination of malignant and nontumor hepatocytes and determine the quantity and timing of hepatocyte shedding into the circulation. Using semiquantitative reverse transcription-PCR for alpha-fetoprotein (afp) and albumin (alb) mRNAs, we measured the mass of malignant and nontumor hepatocytes in 53 peripheral blood samples collected preoperatively, intraoperatively, and postoperatively from 13 HCC patients. We compared these data with those in 54 control samples collected from 24 healthy subjects and patients with chronic hepatitis/cirrhosis and 10 hepatocellular adenoma patients who underwent resection. Clinicopathological information of HCC patients was obtained during 3-year follow-up. In 100% (23 of 23) of HCC and adenoma patients, alb mRNA levels increased 10-10(6)-fold intraoperatively and then markedly declined within 8 weeks after operation. Levels of afp mRNA increased 5-7600-fold preoperatively in 8% (1 of 13) and postoperatively in 70% (9 of 13) of HCC patients. All five HCC patients with persistently elevated afp mRNA levels died from intrahepatic/extrahepatic metastasis, liver recurrence, or persistent HCC within 1 year after surgery. The absence/clearance of afp mRNA in 75 % (six of eight) of survivors was strongly associated with the absence of metastasis/recurrence (P = 0.02). We present evidence that alb-expressing hepatocytes are released intraoperatively into the circulation, and afp-expressing tumor cells are disseminated mostly postoperatively that may potentially be the source of recurrence or metastasis. Sequential quantification of both alb and afp mRNAs may provide insights for risk assessment and prognostic indication.
Adenoma↗
Cellularization in Drosophila melanogaster is disrupted by the inhibition of rho activity and the activation of Cdc42 function.
Regulation of cytoskeletal dynamics is essential for cell shape change and morphogenesis. Drosophila melanogaster embryos offer a well-defined system for observing alterations in the cytoskeleton during the process of cellularization, a specialized form of cytokinesis. During cellularization, the actomyosin cytoskeleton forms a hexagonal array and drives invagination of the plasma membrane between the nuclei located at the cortex of the syncytial blastoderm. Rho, Rac, and Cdc42 proteins are members of the Rho subfamily of Ras-related G proteins that are involved in the formation and maintenance of the actin cytoskeleton throughout phylogeny and in D. melanogaster. To investigate how Rho subfamily activity affects the cytoskeleton during cellularization stages, embryos were microinjected with C3 exoenzyme from Clostridium botulinum or with wild-type, constitutively active, or dominant negative versions of Rho, Rac, and Cdc42 proteins. C3 exoenzyme ADP-ribosylates and inactivates Rho with high specificity, whereas constitutively active dominant mutations remain in the activated GTP-bound state to activate downstream effectors. Dominant negative mutations likely inhibit endogenous small G protein activity by sequestering exchange factors. Of the 10 agents microinjected, C3 exoenzyme, constitutively active Cdc42, and dominant negative Rho have a specific and indistinguishable effect: the actomyosin cytoskeleton is disrupted, cellularization halts, and embryogenesis arrests. Time-lapse video records of DIC imaged embryos show that nuclei in injected regions move away from the cortex of the embryo, thereby phenocopying injections of cytochalasin or antimyosin. Rhodamine phalloidin staining reveals that the actin-based hexagonal array normally seen during cellularization is disrupted in a dose-dependent fashion. Additionally, DNA stain reveals that nuclei in the microinjected embryos aggregate in regions that correspond to actin disruption. These embryos halt in cellularization and do not proceed to gastrulation. We conclude that Rho activity and Cdc42 regulation are required for cytoskeletal function in actomyosin-driven furrow canal formation and nuclear positioning.
Animals↗
The nonreceptor protein tyrosine phosphatase PTP1B binds to the cytoplasmic domain of N-cadherin and regulates the cadherin-actin linkage.
Cadherin-mediated adhesion depends on the association of its cytoplasmic domain with the actin-containing cytoskeleton. This interaction is mediated by a group of cytoplasmic proteins: alpha-and beta- or gamma- catenin. Phosphorylation of beta-catenin on tyrosine residues plays a role in controlling this association and, therefore, cadherin function. Previous work from our laboratory suggested that a nonreceptor protein tyrosine phosphatase, bound to the cytoplasmic domain of N-cadherin, is responsible for removing tyrosine-bound phosphate residues from beta-catenin, thus maintaining the cadherin-actin connection (). Here we report the molecular cloning of the cadherin-associated tyrosine phosphatase and identify it as PTP1B. To definitively establish a causal relationship between the function of cadherin-bound PTP1B and cadherin-mediated adhesion, we tested the effect of expressing a catalytically inactive form of PTP1B in L cells constitutively expressing N-cadherin. We find that expression of the catalytically inactive PTP1B results in reduced cadherin-mediated adhesion. Furthermore, cadherin is uncoupled from its association with actin, and beta-catenin shows increased phosphorylation on tyrosine residues when compared with parental cells or cells transfected with the wild-type PTP1B. Both the transfected wild-type and the mutant PTP1B are found associated with N-cadherin, and recombinant mutant PTP1B binds to N-cadherin in vitro, indicating that the catalytically inactive form acts as a dominant negative, displacing endogenous PTP1B, and rendering cadherin nonfunctional. Our results demonstrate a role for PTP1B in regulating cadherin-mediated cell adhesion.
Actins↗
cAMP-induced morphological changes are counteracted by the activated RhoA small GTPase and the Rho kinase ROKalpha.
Dramatic transient changes resulting in a stellate morphology are induced in many cell types on treatment with agents that enhance intracellular cAMP levels. Thrombin fully protects cells from this inductive effect of cAMP through the thrombin receptor. The protective effect of thrombin was shown to be Rho-dependent. Clostridium botulinum C3 exoenzyme, which inactivates RhoA functions, abolished the ability of thrombin to protect cells from responding to increased cAMP levels. A constitutively activated RhoAV14 mutant protein also prevented cells from responding to cAMP. RhoA can be specifically phosphorylated at Ser-188 by the cAMP-activated protein kinase A (PKA). We demonstrate that RhoAV14A188, which cannot be phosphorylated by PKA in vitro, is more effective than RhoAV14 in preventing cells from responding to cAMP and in inducing actin stress fiber formation. This suggests that PKA phosphorylation of RhoA impairs its biological activity in vivo. ROKalpha, a RhoA-associated serine/threonine kinase can also prevent cells from responding to cAMP with shape changes. Phosphorylation of RhoA by PKA in vitro decreases the binding of RhoA to ROKalpha. These results indicate that RhoA and cAMP have antagonistic roles in regulating cellular morphology and suggest that cAMP-mediated down-regulation of RhoA binding to its effector ROKalpha may be involved in this antagonism.
Cell Line↗