Biomedical subjects
Publications and source records attributed to P Cheung.
A case of a young male Chinese recent migrant with anorexia nervosa and schizophrenia is presented. The relevant diagnostic issues relating to anorexia nervosa among Chinese males and the nature of the relationship between anorexia nervosa and schizophrenia are discussed.
A community survey of the relationship between minor psychiatric morbidity and life events, chronic post-migration stressors, social support and coping style among adult Cambodians living in Dunedin was conducted using the 28-item version of the General Health Questionnaire (GHQ-28) as the case identification instrument. Chronic post-migration stressors, life events, poor coping style and poor social support were all associated with minor psychiatric morbidity. Social support or coping style did not moderate the relationship between life events/post-migration stressors and GHQ caseness, but had an independent relationship with the latter.
OBJECTIVE: The objectives of this study were to determine, among all adult Cambodians living in Dunedin: prevalence of illness aetiology beliefs; psychiatric and physical health status; pattern of use of health services; relationships between use of health services and demographic factors, illness aetiology constructs and health status; and problems encountered and improvements desired in the local health services. METHOD: 223 (i.e. 93.3% of all) adult Cambodians living in Dunedin were assessed, using a structured interview, in relation to their sociodemographic status, illness aetiology beliefs, physical health status and use of health services. The 28-item version of the General Health Questionnaire was used to assess psychiatric status. RESULTS: Subjects held multiple indigenous and Western illness aetiology constructs. Psychiatric morbidity using the 28item of the General Health Questionnaire (GHQ28) cutoff of 3/4 was 15.7%; despite this only six subjects had ever used specialist psychiatric services. Malaria, intestinal parasitic infestations and heart conditions were the three most frequently reported physical problems. Most subjects had used traditional services in Cambodia but very few had used them in New Zealand. Health service was related to duration of stay in New Zealand. Socio-economic status, both physical and psychiatric health status and some illness aetiology constructs. One hundred and forty-two (63.7%) subjects reported problems with use of health services in Dunedin. CONCLUSION: Despite methodological limitations, some useful preliminary data on factors pertaining to use of and satisfaction with health services among Cambodians were collected. Future research should examine family characteristics and the decision-making processes that determine service use.
Viremia, fecal shedding and antibody responses to hepatitis E virus (HEV) infections are poorly understood. To better characterize HEV infections, these responses were examined in 67 patients with acute markers for hepatitis E who were admitted to the Infectious Disease Hospital in Kathmandu, Nepal in 1993. A single stool and multiple sera from each patient were examined using polymerase chain reaction to detect HEV RNA. Sera were also examined for antibodies to HEV. Viremia, fecal shedding, and IgM and IgG to HEV were detected in 93%, 70%, 79%, and 87% of 67 patients, respectively. Viremia or fecal shedding (or both) were detected in 14 patients from whom IgM and IgG to HEV were not detected. Viremia lasted at least 2 weeks in nearly all subjects and at least 39 days in 1 subject. Our results suggest that viremia is a common occurrence in patients infected with HEV.
A community survey examining the relationship between acculturation and minor psychiatric morbidity among 223 Cambodians living in Dunedin, New Zealand was conducted. Most subjects would like to retain their parent culture but would also like to assimilate into the host culture, indicating a preference for an integrated mode of acculturation. Those who were older, widowed, less educated, had shorter duration of stay in New Zealand, and of lower socioeconomic status, were less acculturated. Overall, the least acculturated were found to have the highest rate of psychiatric morbidity. When age and sex were controlled, the association between acculturation and psychiatric morbidity remained significant only for women aged 31 to 50. Overall, the associations between psychiatric morbidity and acculturation held true for marital status, duration of stay in N.Z., educational level, and socioeconomic status. The relevant conceptual and methodological issues in acculturation studies were discussed.
Leflunomide is a novel immunosuppressive compound that is effective in the treatment of animal models of autoimmune disease and human rheumatoid arthritis. The mechanism of action is unknown. Here we show that leflunomide blocked 1) increases in nucleolar size and number, 2) upregulation of the nuclear protein antigens (PCNA and Ki-67), 3) increases in uridine incorporation and total RNA and DNA content, 4) cell cycle progression and 5) proliferation in mitogen-stimulated rat spleen mononuclear cells and human peripheral blood mononuclear cells (HPBMC). Exogenous uridine reversed the leflunomide-dependent inhibition of the normal increase in total RNA and DNA content in mitogen-stimulated HPBMC and rat spleen cells. Uridine reversed the leflunomide-dependent inhibition of cell cycle progression in stimulated rat cell cultures. Either uridine or cytidine, which can be converted to uridine by cytidine deaminase, reversed the antiproliferative effect of leflunomide in HPBMC. Dihydroorotate accumulated in leflunomide-treated human T-lymphoblastoid cells, suggesting that the compound inhibited the fourth enzyme in the pyrimidine biosynthetic pathway, dihydroorotate dehydrogenase. The results support the hypothesis that the in vitro effects of leflunomide on T-lymphocytes are due to inhibition of de novo pyrimidine synthesis.
Actomyosin interactions were examined by using yeast actin mutants with alanines replacing charged amino acid pairs D24/D25, E99/E100, D80/D81, and E83/K84. In the in vitro motility experiments, actin filaments of D24A/D25A or E99A/E100A mutants moved in the presence of 0.7% methylcellulose at the velocities of wild-type actin. Without methylcellulose, these mutant filaments, but not the D80/D81 or E83/K84 filaments, dissociated from the assay surface upon addition of ATP. Measurements of myosin subfragment-1 (S1) binding to D24A/D25A- and E99A/E100A-polymerized actins in the presence of ATP revealed a three- and twofold decrease in their binding constant, respectively, compared with wild-type actin. In contrast to this, all monomeric actins had the same binding affinity for S1. The rates and extents of polymerization of D24A/D25A and E99A/E100A actins by S1 were reduced in comparison to wild-type actin. The local structure of subdomain-2 on actin, as probed by subtilisin cleavage, was not altered for either mutant. A twofold decrease in nucleotide exchange was detected for the D24A/D25A mutant actin. These results demonstrate the involvement of the D24/D25 and E99/E100 residues in the weak binding of myosin to actin and reveal that residues D80/D81 and E83/K84 do not modulate actomyosin interactions.
Explore the source record for details and available documents.
The atomic structure of myosin subfragment-1 (S1) has been recently solved for crystals of extensively methylated S1 [Rayment et al. (1993) Science 261, 50-58]. In this study, the effect of such a modification on S1 structure and function was examined. According to the far- and near-ultraviolet CD spectra, the methylation does not affect the secondary structure of S1 but causes limited changes in its tertiary structure. The methylation significantly decreases the affinity of S1 for actin in rigor and, to a lesser degree, that of S1 to actin in the presence of MgATP gamma S. This modification, like the trinitrophenylation of Lys-83, accelerates the dissociation of a nucleotide trapped on S1 either by phosphate analogs or by cross-linking of the SH1 and SH2 thiols. Methylation strongly impairs the coupling between the actin- and nucleotide-binding sites as revealed by the reduced effect of actin on the release of epsilon ADP from the active site. It also causes a complete loss of in vitro motility of actin filaments over methylated HMM. In addition to this, methylation also impairs the communication between other sites on S1 including that between the nucleotide-binding site and SH1, and the actin-binding site and the 27/50 kDa junction and a site at 74 kDa from the N-terminus of S1. These changes are revealed in SH1 modification, thermolysin digestion, and vanadate-dependent photocleavage experiments, respectively. The increased rate of thermal denaturation of S1 and the loss of S1 protection by ADP and actin from this process also indicate flawed communications in methylated S1. It is concluded that these relatively mild but numerous and important changes impair the function of methylated S1.
Beryllium fluoride (BeFx) has been widely used as a phosphate analogue in nucleotide-binding proteins. It was found to bind tightly to F- but not G-actin (Combeau C., and Carlier M. F. (1988) J. Biol. Chem. 263, 17429-17436) and to affect the three-dimensional structure of filaments by stabilizing the subdomain 2 region of the actin promoter (Orlova, A., and Egelman, E. H. (1992) J. Mol. Biol. 227, 1043-1053). In this work we examined the BeFx-induced structural and functional changes in G- and F-actin by using proteolysis, chemical modifications, ATPase, and in vitro motility assays. The results of proteolysis studies show that BeFx binds also to MgADP-G-actin and renders its subdomain 2 region more similar to that in MgATP-G-actin. This is manifested in enhanced subtilisin and decreased tryptic digestions in subdomain 2 of G-actin. BeFx had a strong effect on the proteolysis of MgADP-F-actin: both the tryptic and subtilisin digestions in subdomain 2 were completely inhibited. Significant protection against proteolysis in this region was observed even at 1:14 molar ratios of BeFx to actin indicating cooperative effects on the structure of the actin filament. A similar although milder effect of phosphate on the proteolysis of F-actin suggests that BeFx acts as a phosphate analogue in this system. BeFx also induces changes in the subdomain 1 region of F-actin. This is revealed via reduced rates of Cys-374 alkylation with 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin and an increased subtilisin cleavage near the C terminus of actin in the presence of BeFx. The BeFx-induced structural changes in actin have little effect on its interactions with myosin. BeFx inhibits only slightly the actin-activated ATPase activity of S1 by decreasing Vmax without affecting KM. Additionally, the binding of BeFx to actin does not change the sliding velocity of actin filaments in the in vitro motility assays. The BeFx-induced specific and distinct changes in G- and F-actin point to the dynamic nature of actin structure and the local differences between monomeric and polymeric forms of actin.
This study confirmed the reliability and validity of a Cambodian version of the 28-item General Health Questionnaire (GHQ-28). The GHQ-28 was tested on 223 adult Cambodians living in Dunedin, New Zealand, who were examined independently by a psychiatrist (P.C.) using the short Present State Examination (PSE). There were satisfactory internal consistencies for the whole scale and the subscales except the C scale. It correctly identified 84.4% of cases with a 3/4 cut-off (sensitivity 87.5%, specificity 82.8%), suggesting a discriminative power as good as its English version when used among Caucasian women in Dunedin. The four subscales were by no means independent, and concurrent validity tests with the PSE suggested that they provided additional information regarding somatic symptoms and anxiety, but not about social dysfunction and depression.
In this study, we use fluorescent probes and proteolytic digestions to demonstrate structural coupling between distant regions of actin. We show that modifications of Cys-374 in the C-terminus of actin slow the rate of nucleotide exchange in the nucleotide cleft. Conformational coupling between the C-terminus and the DNasal loop in subdomain II is observed in proteolytic digestion experiments in which a new C-terminal cleavage site is exposed upon DNasel binding. The functional consequences of C-terminal modification are evident from S-1 ATPase activity and the in vitro motility experiments with modified actins. Pyrene actin, labeled at Cys-374, activates S-1 ATPase activity only half as well as control actin. This reduction is attributed to a lower Vmax value because the affinity of pyrene actin to S-1 is not significantly altered. The in vitro sliding velocity of pyrene actin is also decreased. However, IAEDANS labeling of actin (also at Cys-374) enhances the Vmax of acto-S-1 ATPase activity and the in vitro sliding velocity by approximately 25%. These results are discussed in terms of conformational coupling between distant regions in actin and the functional implications of the interactions of actin-binding proteins with the C-terminus of actin.
The author's objective was to determine the amount of trauma, prevalence and diagnostic features of posttraumatic stress disorder (PTSD), and to study the relationship between PTSD and demographic variables, trauma experiences, coping style and post-migration stresses among adult Cambodian refugees in New Zealand. Information on basic sociodemographic data, trauma experiences, posttraumatic stress symptoms, General Health Questionnaire 28-item version (GHQ-28) scores, coping style, and post-migration stresses were gathered from 223 adult Cambodian refugees living in Dunedin, New Zealand. Most subjects had experienced multiple, severe traumas. The prevalence of PTSD was 12.1%. The most frequently reported posttraumatic stress symptom was recurrent intrusive recollection of trauma. There was a significant association between PTSD and amount of trauma, coping style, and post-migration stresses.
OBJECTIVE: To assess the feasibility of obtaining continuous wave Doppler measurements of aortic bloodflow from the suprasternal notch during upright treadmill exercise as an objective adjunct to cardiac performance and functional capacity in heart failure. DESIGN: Prospective descriptive study. SETTING: University teaching hospital out-patient heart failure clinic. PATIENTS: Fifty-three patients with New York Heart Association (NYHA) class II or III heart failure (left ventricular ejection fraction 9 to 37%) and 15 control subjects of similar age but without heart disease. INTERVENTION: Symptom-limited (or to completion of 22-min protocol) treadmill exercise using a modified Naughton protocol. RESULTS: Exercise duration was 11.3 +/- 0.6 mins for heart failure and 20.5 +/- 0.6 mins for normals. Both within subject and interobserver variability for the Doppler derived variables were satisfactory. There were no significant differences at rest between groups for any of the measured Doppler variables. In heart failure patients compared with normals, significant reductions in stroke distance and peak velocity occurred during stage I and in peak acceleration during stage II and persisted throughout exercise with reductions in maximum achieved peak velocity (0.64 +/- 0.02 versus 0.97 +/- 0.05 m/s, P < 0.001), peak acceleration (19.0 +/- 0.9 versus 37.3 +/- 2.4 m/s2, P < 0.001) and stroke distance (7.5 +/- 0.3 versus 11.2 +/- 0.6 cm, P < 0.001). Receiver operator curves had very favourable discriminating characteristics. No significant differences in Doppler indices were observed between patients due to etiology of heart failure or NYHA functional class. CONCLUSION: Aortic bloodflow indices can be reliably measured from the suprasternal notch during upright treadmill exercise in the majority of heart failure patients. Since the indices were abnormal even at very early stages of exercise, further studies are required to define their usefulness as an adjunct in the assessment of heart failure patients whose maximum exercise tolerance is limited by other factors such as arthritis, intermittent claudication or lung disease.
A cDNA (rc75) encoding a 75-kDa rabbit zona pellucida (ZP) glycoprotein (R75) has been cloned and sequenced. The predicted amino acid sequence consists of 676 amino acids including seven potential N-glycosylation sites. The cDNA hybridizes to a 2.4-kilobase mRNA in ovary that is not detectable in other rabbit tissues. The R75 mRNA was also found to be expressed during the early stages of rabbit ovarian development (2-6 weeks of age) when the ovary contains primordial, primary, and early secondary follicles. The deduced amino acid sequence of rc75 has 77% similarity to the mouse ZP2 protein but no similarity to mouse ZP3. R75 also contains regions with 35-55% similarity to a previously cloned rabbit 55-kDa ZP protein. Monte Carlo simulation comparison confirmed that R75 has a significant probability of homology with mouse ZP2 and the rabbit 55-kDa ZP protein. Antibodies were developed against a fragment of R75 (rc75a cDNA) expressed in the pEX expression vector. These antibodies were used to confirm that the expressed protein contained epitopes found in the native rabbit ZP glycoprotein. These data suggest that some, but not all, ZP proteins may be conserved among different species and that within a species ZP proteins may share similar regions.
The effect of prophylactic treatment with depot antipsychotic drugs was examined in 16 patients with bipolar affective disorder. The frequency and duration of illness episodes occurring during depot treatment was compared to that which occurred when these patients were treated with other agents over a corresponding time period. Treatment with depot antipsychotics was associated with a significant decrease in the frequency and duration of manic episodes, but not depressive episodes. Thus prophylactic treatment with depot antipsychotic drugs is likely to be of benefit in patients with bipolar illness who experience frequent manic episodes despite treatment with lithium and/or carbamazepine.
Three Cambodian patients with Depression and Post-traumatic Stress Disorder (PTSD) presenting with somatic complaints are described. Their case histories support previous observations that somatisation is the most common presentation of Cambodian patients with Depression and PTSD. The probable reasons why depressed, traumatised Cambodian patients somatise their psychiatric problems are discussed. These cases illustrate the difficulties involved in engaging such patients in Western style psychotherapy, but show the effectiveness of small doses of antidepressants in treating the depressive and post-traumatic stress symptoms.
A synthetic peptide corresponding to a sequence 632-642 (S632-642) on the myosin subfragment 1 (S-1) heavy chain and spanning the 50/20 kDa junction of S-1 binds to actin in the presence and absence of S-1. The binding of 1.0 mole of peptide per actin causes almost complete inhibition of actomyosin ATPase activity and only partial inhibition of S-1 binding to actin. The binding of S632-642 to the N-terminal segment of actin is supported by competitive carbodiimide cross-linking of S-1 and S632-642 to actin and the catalytic properties of cross-linked acto-S-1 and actin-peptide complexes. These results show that the sequence 632-642 on S-1 is an autonomous binding site for actin and confirm the catalytic importance of its interactions with the N-terminal segment of actin.