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Biomedical subjects

A Cheng

Publications and source records attributed to A Cheng.

At least 55 records · Page 3Linked to original sources

The use of abciximab in coronary angioplasty--an Asian centre's experience.

BACKGROUND: Abciximab, a monoclonal antibody to platelet glycoprotein IIb/IIIa receptor, has been shown to be effective in reducing ischemic complications after coronary angioplasty in recent trials. However, little is known about its efficacy and safety when used in Asian patients. METHODOLOGY: Based on our abciximab registry, we performed a retrospective analysis of 115 Asian patients who received the antiplatelet agent while undergoing percutaneous coronary intervention in our centre. They constituted 18.4% of the total number of patients undergoing percutaneous revascularisation during the corresponding period. The majority of the patients were males (84%). The mean age of the cohort was 54 and the mean weight was 70 kg. The ethnic composition of the study population was: Chinese 54%, Indians 21%, Malays 19% and Others 6%. All patients received aspirin 100 mg and weight-adjusted heparin before the procedure. Abciximab may be administered on a preplanned basis prior to the procedure or be given as a 'bailout' strategy. RESULTS: There was a high clinical success rate of 95.8% and low incidence of ischemic complications when abciximab was given during coronary angioplasty. There were 0% Q myocardial infarction, 3.3% non-Q myocardial infarction and 0.8% death in our series. Bleeding complications were uncommon at 7.6%, predominantly involving the groin and gingiva. Thrombocytopenia occurred in 5.8% of patients. Abciximab was noted to increase the procedural activated clotting time (ACT) by 38 seconds when given concomitantly with heparin. The mean maximal procedural ACT achieved was 323 +/- 51 seconds. CONCLUSIONS: Abciximab may be used safely and efficaciously in Asian patients undergoing coronary angioplasty. The drug confers protection against ischemic complications during the procedure whether it is administered electively or as a 'bailout'. There is however, a need to redefine the heparin regime for our patients, given the high ACT obtained when abciximab is administered.

Abciximab↗

Development of an affordable diaphragmatic pump for cardiopulmonary bypass: an in vivo evaluation.

A new diaphragmatic pump (L-Y pump) and its drive unit were developed in our institute. The pump has a priming volume of 80 ml. The pump housing is 72 mm in diameter and 42 mm in height. Its total weight is 139 g. To assess and confirm the function and controllability of this pump, comparative studies of cardiopulmonary bypass (CPB) with L-Y pump (group A) and conventional roller pump (Group B) were performed using dogs. Both pumps provided pump flow of 90 to 100 ml/kg/min. The hemodynamics of both groups were stable and within the normal range. No leakage or thrombus formation was observed in the L-Y pump. All biochemistry data showed no significant differences between the 2 groups. This data demonstrated low plasma-free hemoglobin levels in the L-Y pump group; after 120 min of CPB, mean plasma free hemoglobin levels were 48.7 +/- 8.6 mg/dl in the roller pump group and 21.4 +/- 7.1 mg/dl in the L-Y pump group, and minimal hemolysis was indicated. In conclusion, this L-Y pump and its controller system might be useful for CPB in terms of its low hemolysis and good pump quality. This pump demonstrated easy manipulation, good controllability, and provided a sufficient pulsatile flow. This pump is suitable not only for CPB, but also as a long-term circulatory support system.

Animals↗

Menopausal symptoms and symptom clustering in Chinese women.

OBJECTIVES: this paper aims to report the prevalence of symptoms in the Hong Kong Chinese perimenopausal women; to construct reported symptoms into symptom groupings; and to clarify whether the symptom groups are associated with menopausal status. METHODS: a random telephone survey of perimenopausal women aged 44-55 years was conducted in 1996. Eligible subjects were identified through telephone dialing of a random sample of the numbers listed in the residents' telephone directory. Standardized questionnaire, including a 22-item symptom check list, was administered over the telephone. The principal component analysis method followed by varimax rotation was used to examine the relations among the symptoms. RESULTS: differences in the prevalence of menstrual problems across the menopausal status were noted with perimenopausal women having the most complaints. Musculoskeletal conditions were the top complaints reported by the respondents, followed by headaches and psychological symptoms. About 10% of the women complained of hot flushes, and less than 5% of cold sweats. Five symptom clusters, namely psychological, musculoskeletal/gastrointestinal, non-specific somatic, respiratory, and vasomotor, have been identified. After adjustment for age, the analysis of variance showed that psychological, non-specific somatic and vasomotor symptoms were significantly associated with menopausal status, while musculoskeletal and respiratory were of borderline statistical significance. CONCLUSIONS: compared with pre- and post-menopausal women, perimenopausal women had the highest reports of symptom complaints. Musculoskeletal complaints were the most prevalent complaints, followed by psychological symptoms. While vasomotor symptoms were significantly associated with menopausal status, their prevalence was comparatively lower than that reported in Caucasian populations.

Adult↗

Dephosphorylation of cyclin-dependent kinases by type 2C protein phosphatases.

Activating phosphorylation of cyclin-dependent protein kinases (CDKs) is necessary for their kinase activity and cell cycle progression. This phosphorylation is carried out by the Cdk-activating kinase (CAK); in contrast, little is known about the corresponding protein phosphatase. We show that type 2C protein phosphatases (PP2Cs) are responsible for this dephosphorylation of Cdc28p, the major budding yeast CDK. Two yeast PP2Cs, Ptc2p and Ptc3p, display Cdc28p phosphatase activity in vitro and in vivo, and account for approximately 90% of Cdc28p phosphatase activity in yeast extracts. Overexpression of PTC2 or PTC3 results in synthetic lethality in strains temperature-sensitive for yeast CAK1, and disruptions of PTC2 and PTC3 suppress the growth defect of a cak1 mutant. Furthermore, PP2C-like enzymes are the predominant phosphatases toward human Cdk2 in HeLa cell extracts, indicating that the substrate specificity of PP2Cs toward CDKs is evolutionarily conserved.

CDC28 Protein Kinase, S cerevisiae↗

Estimating the mass of asteroid 433 eros during the NEAR spacecraft flyby

The Near Earth Asteroid Rendezvous (NEAR) spacecraft flew within 3830 kilometers of asteroid 433 Eros on 23 December 1998. The gravitational perturbation on NEAR was evident in the spacecraft tracking data. Ground-based Doppler and range tracking of the spacecraft as well as spacecraft images of the asteroid's center of figure and surface features were used to determine the mass and rotation pole of Eros. The mass of Eros is (7.2 +/- 1.8) x 10(18) grams and, coupled with a volume estimate provided by the NEAR imaging team, this mass suggests a bulk density of 2.5 +/- 0.8 grams per cubic centimeter. The rotation pole position is 15.6 (+/-3.7) degrees in right ascension and 16.4 (+/-1.8) degrees in declination, which is consistent with ground-based and NEAR imaging team observations.

Journal Article↗

Imaging of asteroid 433 eros during NEAR's flyby reconnaissance

During the 23 December 1998 flyby of asteroid 433 Eros, the Near-Earth Asteroid Rendezvous (NEAR) spacecraft obtained 222 images of Eros, as well as supporting spectral observations. The images cover slightly more than two-thirds of Eros (best resolution is approximately 400 meters per pixel) and reveal an elongated, cratered body with a linear feature extending for at least 20 kilometers. Our observations show that Eros has dimensions of 33 x 13 x 13 kilometers. The volume, combined with the mass determined by the NEAR radio science experiment, leads to a density of 2.5 +/- 0.8 grams per cubic centimeter. This relatively high density, and the presence of an extensive linear feature, suggest that Eros may be a structurally coherent body.

Journal Article↗

In vivo human brachial artery elastic mechanics: effects of smooth muscle relaxation.

BACKGROUND: The effects of smooth muscle relaxation on arterial wall mechanics are controversial. We used a new, in vivo, noninvasive technique to measure brachial artery wall mechanics under baseline conditions and following smooth muscle relaxation with nitroglycerin (NTG). METHODS AND RESULTS: Eight healthy, normal subjects (6 male, 2 female; age 30+/-3.1 years) participated in the study. The nondominant brachial artery was imaged through a water-filled blood pressure cuff using an external ultrasound wall-tracking system at baseline and following 0.4 mg sublingual NTG. Simultaneous radial artery pressure waveforms were recorded by tonometry. Transmural pressure (TP) was reduced by increasing water pressure in the cuff. Brachial artery area, unstressed area, compliance, stress, strain, incremental elastic modulus (Einc), and pulse wave velocity (PWV) were measured over a TP range from 0 to 100 mm Hg. Baseline area versus TP curves generated 30 minutes apart were not significantly different. NTG significantly shifted area versus TP (P<0.0001) and compliance versus TP (P<0.001) curves upward, whereas the Einc versus TP (P<0.05) and PWV versus TP (P<0. 01) curves were shifted downward. NTG also significantly shifted stress versus strain (P<0.01) and Einc versus strain (P<0.01) curves to the right. CONCLUSIONS: We conclude that brachial artery elastic mechanics can be reproducibly measured over a wide range of TP and smooth muscle tone using a new noninvasive ultrasound technique. Smooth muscle relaxation with NTG increases isobaric compliance and decreases isobaric Einc and PWV in the human brachial artery.

Adult↗

MAP5 expression in proliferating neuroblasts.

MAP5, a microtubule-associated protein present in immature neurons, was found to be expressed in the embryonic mouse telencephalic ventricular zone (VZ). Since the VZ contains proliferating neuroblasts, the source of most of the neurons of the cerebral cortex, this observation raised the possibility that MAP5 is expressed by proliferating neuronal progenitors. MAP5-positive mitotic cells were observed at the ventricular surface, a finding consistent with progenitors expressing MAP5 prior to their last division. This possibility was investigated using dissociated, cortical cells in vitro by measuring the expression of MAP5 and the neuroepithelial marker nestin, together with the incorporation of bromodeoxyuridine (BrdU), a thymidine analogue that labels the DNA of proliferating cells in the S-phase of the cell cycle. All of the proliferating cells expressed nestin. A population of MAP5-positive cells was also found to incorporate BrdU; some cells expressed MAP5 within 30 min of BrdU labeling. The results suggest that uncommitted neuroblasts express only nestin, with expression of MAP5 occurring near the time the cell commits to become a postmitotic neuron after the next cell division. Subsequently, cells expressing both MAP5 and nestin leave the cell cycle and exit the VZ, lose nestin, and differentiate into neurons. Since some cells expressed MAP5 during or shortly after S-phase but before mitosis, MAP5 may be the earliest marker to identify neuronal progenitors that will become post-mitotic neurons following their next mitosis.

Animals↗

Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene.

Protein tyrosine phosphatase-1B (PTP-1B) has been implicated in the negative regulation of insulin signaling. Disruption of the mouse homolog of the gene encoding PTP-1B yielded healthy mice that, in the fed state, had blood glucose concentrations that were slightly lower and concentrations of circulating insulin that were one-half those of their PTP-1B+/+ littermates. The enhanced insulin sensitivity of the PTP-1B-/- mice was also evident in glucose and insulin tolerance tests. The PTP-1B-/- mice showed increased phosphorylation of the insulin receptor in liver and muscle tissue after insulin injection in comparison to PTP-1B+/+ mice. On a high-fat diet, the PTP-1B-/- and PTP-1B+/- mice were resistant to weight gain and remained insulin sensitive, whereas the PTP-1B+/+ mice rapidly gained weight and became insulin resistant. These results demonstrate that PTP-1B has a major role in modulating both insulin sensitivity and fuel metabolism, thereby establishing it as a potential therapeutic target in the treatment of type 2 diabetes and obesity.

Animals↗

Secondary prevention of myocardial infarction: role of beta-adrenergic blockers and angiotensin-converting enzyme inhibitors.

beta-Blockers reduce cardiovascular death and reinfarction in patients with a history of myocardial infarction (MI), and angiotensin-converting enzyme (ACE) inhibitors provide an overall survival benefit in patients with signs or symptoms of left ventricular (LV) dysfunction and a history of acute MI. Despite this, these agents remain underused in clinical practice. Appropriate patient selection in standard clinical practice should be encouraged in order to achieve a mortality rate reduction comparable to that seen in clinical trials. It appears from the findings of recent studies that the greatest benefit from beta-blocker therapy is achieved in patients who are more than 60 years of age and in patients at moderate or high risk for reinfarction and death (eg, patients with LV dysfunction or arrhythmias or both). Patients with class I-IV heart failure treated with ACE inhibitors have fewer recurrent infarctions, a lower incidence of severe congestive heart failure, and a reduced incidence of total cardiovascular death and sudden cardiac death. In addition to the studies completed in patients with MI, there are ongoing studies evaluating whether or not ACE inhibitors can reduce myocardial ischemic events in patients without a prior infarction who have coronary artery disease or hypertension and preserved LV function. There is also growing evidence that concomitant therapy with a beta-blocker and an ACE inhibitor may reduce mortality rates beyond that observed with ACE inhibitors alone in survivors of MI who have LV dysfunction.

Adrenergic beta-Antagonists↗

Janus kinases and their role in growth and disease.

Janus kinases (JAK) play a crucial role in the initial steps of cytokine signaling. Each of the four members (JAK1, JAK2, JAK3, TYK2) of this non-receptor tyrosine kinase family is indispensable for the effects of distinct cytokines. Moreover, recent reports have added to our knowledge on their highly specific functions: JAK3 knockout mice and JAK3 deficient patients cannot signal through the interleukin-2,4,7,9, or 15 receptors and suffer from severe combined immunodeficiency (SCID). JAK1 and JAK2 knockout mice do not survive, their cells again showing distinct patterns of cytokine signaling deficits. At the other end of the spectrum, JAK fusion proteins have been shown to play a role in leukemias. In addition, a new class of JAK-specific inhibitors was described by several groups, the CIS/SOCS/Jab family. This review on the rapidly growing field focuses on JAK function and regulation, and on their emerging role in development and human disease.

Animals↗

A patient-derived mutant form of the Fanconi anemia protein, FANCA, is defective in nuclear accumulation.

Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with at least eight complementation groups (A-H). Three FA genes, corresponding to complementation groups A, C, and G, have been cloned, but the function of the encoded FA proteins remains unknown. We recently demonstrated that the FANCA and FANCC proteins bind and form a nuclear complex. In the current study, we identified a homozygous mutation in the FANCA gene (3329A>C) in an Egyptian FA patient from a consanguineous family. This mutant FANCA allele is predicted to encode a mutant FANCA protein, FANCA(H1110P), in which histidine 1110 is changed to proline. Initially, we characterized the FANCA(H1110P) protein, expressed in an Epstein Barr virus (EBV)-immortalized lymphoblast line derived from the patient. Unlike wild-type FANCA protein expressed in normal lymphoblasts, FANCA(H1110P) was not phosphorylated and failed to bind to FANCC. To test directly the effect of this mutation on FANCA function, we used retroviral-mediated transduction to express either wild-type FANCA or FANCA(H1110P) protein in the FA-A fibroblast line, GM6914. Unlike wild-type FANCA, the mutant protein failed to complement the mitomycin C sensitivity of these cells. In addition, the FANCA(H1110P) protein was defective in nuclear accumulation in the transduced cells. The characteristics of this mutant protein underscore the importance of FANCA phosphorylation, FANCA/FANCC binding, and nuclear accumulation in the function of the FA pathway.

Amino Acid Substitution↗

Residential characteristics influence Der p 1 levels in homes in Melbourne, Australia.

BACKGROUND: Exposure to house dust mite (HDM) allergens is an important risk factor for childhood asthma. Knowledge of environmental determinants of HDM allergen levels is essential before designing rational avoidance measures. AIM: To investigate the effect of domestic characteristics on HDM allergen (Der p 1) levels in Melbourne homes. METHODS: Dust was collected from bed and floor of the bedrooms in 485 houses over a period of one year. Dust was analysed for Der p 1 levels using an enzyme-linked immunosorbent assay. Temperature and relative humidity were measured at the visit. Details of residential characteristics were collected using a questionnaire. Statistically significant predictors of Der p 1 levels (P < 0.05) were identified using multiple linear regression. RESULTS: High levels of Der p 1 were observed in the floors (geometric mean 17.2 microg/g fine dust) as well as in the beds (geometric mean 20.3 microg/g fine dust). Der p 1 levels in the floor dust were significantly lower in winter and spring. They were higher in houses built before 1980 and those with central heating, weather board walls, damp bedrooms or fitted old wool carpets. Der p 1 levels in bed dust were significantly higher in houses built before 1980, with wooden floors built on stumps, with high relative humidity, with visible mould in the room, in beds with an old mattress or in beds without a quilt. CONCLUSIONS: We would encourage construction of homes without carpets, wooden floors on stumps or weather board walls.

Allergens↗

Seasonal differences in risk factors for sudden infant death syndrome. The New Zealand Cot Death Study Group.

The aim of this study was to explore whether the risk of sudden infant death syndrome (SIDS) associated with prone sleeping position and other risk factors varies with season. The study was a large nation-wide case-control study, which compared 485 cases with 1800 controls. Parents of 393 (81.0%) cases and 1591 (88.4%) controls were interviewed. Obstetric records were also examined. Infants dying in winter were older and had lower birthweights than those dying in summer. The increased risk of SIDS associated with prone sleeping position was greater in winter than in summer. In contrast, the increased risk of SIDS associated with excess thermal insulation and bed sharing was less in winter than in summer. Prone sleeping position accounts for about half of the difference between the mortality rate in summer and that in winter. This suggests that some factor related to season modifies the effect of prone sleeping position.

Age Distribution↗

A reliable and valid home visit report for studies of asthma in young adults.

Validated instruments are not available to assess the residential characteristics. The aim of this study was to assess the reliability and validity of an interviewer-administered home visit report. The validity of 48 items in the Home Visit Report was examined against: observations made by a researcher, measurements of relative humidity, cat allergen, and ergosterol, a biomaker of fungal exposure and a biochemical test. Test-retest reliability of 10 fixed residential characteristics was assessed comparing the responses obtained in the main study with the pilot study, Kappa, ANOVA and Wilcoxon Rank Sum tests were applied to assess the agreement and P < 0.05 was considered as statistically significant. Among 44 items examined for the validity against observations, there was a perfect or almost perfect agreement in 21 (kappa = 0.9-1) and substantial agreement (kappa = 0.6-0.8) in 19. Higher cat allergen levels were observed with cat ownership and cat being allowed indoors. Observed condensation was associated with relative humidity and observed mould was associated with ergosterol levels. The agreement on the type of carpet and the test was substantial (kappa = 0.6). Among 10 items examined for reliability, there was a perfect or almost perfect agreement in 9 (kappa = 0.9-1) and substantial agreement (kappa = 0.7) in one. In conclusion, the Home Visit Report validated in this study provides reliable and valid data.

Adult↗

Sexual dimorphism in the neonatal gonad.

The neonatal gonad has two distinct forms (i.e., is sexually dimorphic), as judged by morphological and endocrine characteristics. The dimorphic process begins early in embryogenesis. It is well established by the time of birth, by which time the genital ridge has developed into either a testis or an ovary. The mechanisms involved in sex determination involve the Y chromosome, autosomal genes, transcription factors and possibly other unidentified control networks. This review paper describes the morphological changes that occur and the endocrine functions in the developing gonads. It highlights a number of important differences in fetal and neonatal gonadal function. The testis has early histological definition, several determining genes, delayed germ cell maturation, early autonomous steroid secretion, luteinizing hormone (LH) receptor and steroid enzyme expression, high fetal testicular testosterone content, prominent postnatal Leydig and Sertoli cells and high postnatal serum testosterone levels. The ovary has a prolonged monomorphic state, probably one determining gene, germ cells in early meiotic arrest, delayed expression of LH receptor and aromatase, low ovarian oestradiol content, prominent postnatal follicles and low postnatal serum oestradiol levels.

Embryonic and Fetal Development↗

Assessment of the gonadotrophin-gonadal axis in androgen insensitivity syndrome.

OBJECTIVE: To study the value of measuring serum luteinising hormone (LH), follicle stimulating hormone (FSH), testosterone, and dihydrotestosterone (DHT) in androgen insensitivity syndrome (AIS). DESIGN: Retrospective study of patients on a nationwide register of AIS. PATIENTS: Sixty one cases of AIS with androgen receptor (AR) dysfunction (abnormalities of the AR gene and/or abnormal AR binding) were divided into three age groups: infants, < 1 year old; children, 1-13 years old; and postpubertal, > 13 years old. MEASUREMENTS: Age, dose of human chorionic gonadotrophin (hCG) stimulation, pre-hCG and post-hCG serum testosterone values, serum DHT values, and serum LH and FSH values before and after LH releasing hormone (LHRH) stimulation. RESULTS: In 23 of 30 infants testosterone was within age related reference ranges; six were above this range. The median testosterone rise following variable dosage of hCG was 9.5 times the basal value. The increment was not related to the hCG dose, age, or basal concentration of testosterone. The median basal and stimulated testosterone:DHT ratios were 2.5 and 6.1, respectively. The median increment in DHT was 2.2-fold. Seventeen of 18 FSH and 11 of 19 LH measurements were within age related ranges in infants; in seven patients LH values were above the range. LHRH stimulation performed in 39 patients showed an exaggerated LH in all age groups. The FSH response was not exaggerated in children. CONCLUSION: Although a positive hCG test excludes biosynthetic defects of testosterone, an inadequate response does not exclude AIS. Basal LH and testosterone may not be raised during early infancy. An LHRH stimulation test might be useful for evaluating cases of suspected AIS presenting in mid-childhood.

Adolescent↗