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Biomedical subjects

A Cheng

Publications and source records attributed to A Cheng.

At least 37 records · Page 2Linked to original sources
PubMed2000

Modulation of insulin signaling by protein tyrosine phosphatases.

Non-insulin-dependent diabetes mellitus (NIDDM) is a worldwide endocrine disorder afflicting persons of all races and age groups. At the molecular level NIDDM is often characterized by impaired insulin action on peripheral tissues. One important mechanism in regulating insulin signaling is mediated by protein tyrosine phosphatases, which may act on the insulin receptor itself and/or its substrates. Understanding the molecular events triggered by insulin has undoubtedly provided important clues in the treatment of NIDDM. In particular, the use of mouse models has helped us to focus on specific gene targets that are involved in the onset and progression of diabetes. Here we present an overview of the biochemical and genetic evidence supporting the role of five protein tyrosine phosphatases in insulin-mediated responses.

Animals↗
PubMed2000

Epidemiology of cervical and trochanteric fractures of the proximal femur in 1994 in Tangshan, China.

The purpose of this study was to determine the incidence of cervical and trochanteric fractures of the proximal femur in 1994 in Tangshan City, China. There are many reports on hip fracture incidence in many countries, suggesting that there are many factors affecting hip fractures. We visited 15 hospitals with an orthopaedic department within Tangshan City, and reviewed the medical records and radiographs of all patients with hip fractures occurring between January 1 and December 31, 1994. The population of Tangshan in 1994 was determined to be 1,454,543 (746,015 males and 708,528 females). The population of those over 65 years of age was 88,490 (41,519 males and 46,971 females), representing 6.08% of the total population. This study detected 184 cervical and trochanteric fractures of the proximal femur in 1994 in Tangshan (127 men and 57 women). The overall incidence or rate of the combined number of cervical and trochanteric fractures was 25 fractures per 100,000 population per year for men and 12 for women. There were a total of 147 cervical fractures (80%) and 37 trochanteric fractures (20%). The incidence of the combined number of cervical and trochanteric fractures in patients over 70 years of age increased to 108 for men and 156 for women. The incidence of hip fractures increased with age in both sex groups, especially in women over 65. Severe trauma fractures happened more often in younger groups, and mainly occurred in men, which may be a result of the particular composition of the population in Tangshan, which is young and male dominated. In addition, because Tangshan is an industrial city, many of its citizens are involved in occupations requiring a high level of physical activity.

Age Distribution↗
PubMed2000

Laparoscopy in the "normal" infertile patient: a question revisited.

STUDY OBJECTIVE: To determine the prevalence of reproductive pathology in a group of infertile women thought to be at low risk for altered pelvic anatomy. DESIGN: Retrospective chart review and follow-up (Canadian Task Force classification II-2). SETTING: Academic-affiliated, private reproductive endocrinology practice. PATIENTS: One hundred infertile women. INTERVENTION: Diagnostic and/or therapeutic laparoscopy. MEASUREMENTS AND MAIN RESULTS: Of 100 patients with a negative reproductive work-up up to the point of laparoscopy, 68 had pathology of reproductive significance: intrinsic tubal disease 24, peritubal adhesive disease 34, and endometriosis 43, some in combination. Laparoscopy was especially helpful in establishing treatment protocols for older women, who were referred for assisted reproductive techniques earlier than otherwise might have been the case. Women conceived after hormone therapy and after operative intervention. Although the hysterosalpingogram was read as normal in all women, tubal disease was diagnosed laparoscopically, independent of endometriosis, in 27 patients, with 2 having complete obstruction. Endometriosis stage I-II was found in 22 patients, stage III in 13, and stage IV in 6. CONCLUSION: Even in women thought to be at low risk for significant pelvic pathology affecting reproduction, the yield was high. Although some pregnancies were achieved after operative intervention, frequently laparoscopy was helpful in making a decision to go to assisted reproductive technology, particularly when infertility had been of long duration and in older women. Frequently the degree of pathology was such that a full operating suite was necessary to provide adequate instrumentation and anesthesia for operative intervention, which would not have been the case with office laparoscopy.

Adult↗
PubMed2000

GB/SA water model for the Merck molecular force field (MMFF).

A revised generalized Born/surface area (GB/SA) continuum solvation model has been developed for water that is compatible with the Merck molecular force field (MMFF). This model gives free energies of aqueous solvation that are comparable in accuracy to the original water model when the OPLS* force field is employed. The average unsigned error in aqueous deltaGsol using the new water model and MMFF is 0.62 kcal/mol for a training set of 82 solutes compared to 1.24 kcal/mol for the original GB/SA water model and MMFF. The average unsigned errors for 47 neutral solutes outside the training set and 10 ions are 0.96 and 2.32 kcal/mol, respectively. By comparison, the average errors for the test set and ions using the original GB/SA water model are 1.76 and 5.32 kcal/mol. This revised parameter set provides a more accurate representation of aqueous solvation for use with MMFF.

Artificial Intelligence↗
PubMed2000

Pathways from emotional adjustment to glycemic control in youths with diabetes in Hong Kong.

OBJECTIVE: To examine factors that influence emotional adjustment, adherence to diabetic care, and glycemic control in Hong Kong youths with insulin-dependent diabetes mellitus (IDDM). METHODS: Seventy youths, their mothers, and matched controls provided information on health beliefs, authoritarian parenting style, parent-child conflict, emotional adjustment, and adherence to medical regimen. Glycosylated hemoglobin levels were obtained to measure glycemic control. RESULTS: Predictors explained 34% of the variance in emotional adjustment and 39% of the variance in glycemic control. The data supported a pathway from emotional adjustment to self-efficacy to adherence behaviors to glycemic control. In contrast to Western culture and consistent with prediction, parenting style did not associate with negative outcomes, and even relatively low levels of parent-child conflict correlated negatively with emotional adjustment in this culture. CONCLUSIONS: Management of conflict and self-efficacy enhancing interactions are suggested interventions to enhance adherence to diabetic care in Hong Kong youths with IDDM.

Adaptation, Psychological↗
PubMed2000

Complex effects of naturally occurring mutations in the JAK3 pseudokinase domain: evidence for interactions between the kinase and pseudokinase domains.

The structure of Janus kinases (JAKs) is unique among protein tyrosine kinases in having tandem, nonidentical kinase and pseudokinase domains. Despite its conservation in evolution, however, the function of the pseudokinase domain remains poorly understood. Lack of JAK3 expression results in severe combined immunodeficiency (SCID). In this study, we analyze two SCID patients with mutations in the JAK3 pseudokinase domain, which allows for protein expression but disrupts the regulation of the kinase activity. Specifically, these mutant forms of JAK3 had undetectable kinase activity in vitro but were hyperphosphorylated both in patients' Epstein-Barr virus-transformed B cells and when overexpressed in COS7 cells. Moreover, reconstitution of cells with these mutants demonstrated that, although they were constitutively phosphorylated basally, they were unable to transmit cytokine-dependent signals. Further analysis showed that the isolated catalytic domain of JAK3 was functional whereas either the addition of the pseudokinase domain or its deletion from the full-length molecule reduced catalytic activity. Through coimmunoprecipitation of the isolated pseudokinase domain with the isolated catalytic domain, we provide the first evidence that these two domains interact. Furthermore, whereas the wild-type pseudokinase domain modestly inhibited kinase domain-mediated STAT5 phosphorylation, the patient-derived mutants markedly inhibited this phosphorylation. We thus conclude that the JAK3 pseudokinase domain is essential for JAK3 function by regulating its catalytic activity and autophosphorylation. We propose a model in which this occurs via intramolecular interaction with the kinase domain and that increased inhibition of kinase activity by the pseudokinase domain likely contributes to the disease pathogenesis in these two patients.

Amino Acid Sequence↗
PubMed2000

Cardiovascular drug therapy in patients with hepatic diseases and patients with congestive heart failure.

Hepatic impairment can alter the pharmacokinetic profiles of cardiovascular drugs, which can lead to unwanted toxicity. In the presence of cirrhosis, portosystemic shunting occurs and cytochrome P450 activity is reduced. Impaired oxygen uptake caused by changes in the liver's sinusoids, as proposed by the oxygen limitation theory, may also explain the alteration of drug metabolism seen in cirrhosis. With congestive heart failure, sinusoidal congestion and hypoperfusion of the liver are seen. Similar to cirrhosis, the common pathway for hepatic damage in congestive heart failure seems to be liver hypoxia, which may explain the disease's effect on drug metabolism. Since routine hepatic function tests do not always relate to the liver's ability to eliminate drugs, existing guidelines for dosing cardiovascular drugs in patients with hepatic impairment are limited. This article provides guidance for dosing cardiovascular drugs in cirrhotic and heart failure patients based on available research data. Altered drug metabolism, especially in congestive heart failure, tends to be overlooked or not realized in clinical practice. Therefore, further research is needed in congestive heart failure to better elucidate safe prescribing patterns.

Cardiovascular Agents↗
PubMed2000

Phenotypic features, androgen receptor binding, and mutational analysis in 278 clinical cases reported as androgen insensitivity syndrome.

Androgen insensitivity syndrome (AIS) is the most common single entity that results in male under-masculinization, but large cohort studies of AIS have rarely been performed. Over the last decade, nationwide cooperation between pediatric endocrinologists in the United Kingdom has allowed the creation of a database of cases of intersex and ambiguous genitalia where detailed clinical information on every notified case has been collected via a questionnaire. Among the 816 entries recorded by January 1999, there were 105 clinically diagnosed cases of complete AIS (CAIS) and 173 cases of partial AIS (PAIS). A masculinization score was devised by scoring the external phenotype, and a score of 12 represented normal masculinization. Androgen receptor (AR) binding was determined by studying binding capacity (Bmax) and receptor affinity (K(d)), and cases were classified as either zero, abnormal, or normal binding. Mutation screening of all eight exons of the AR gene was performed by single-strand conformational polymorphism analysis, followed by direct DNA sequencing. All cases of PAIS presented within the first month of birth. The median age at presentation of children with CAIS was 1 yr (P10,P90: 0.1,10.4). The testes were palpable in the labioscrotal folds or the inguinal region in 77% and 41% of cases of CAIS and PAIS, respectively. There was marked overlap between the masculinization score of those children with PAIS reared as girls [2.5(P10,P90:1, 6)] and those reared as boys [3(P10,P90:2, 7.5)]. Gonadectomy was performed prepubertally in 66% and postpubertally in 29% of the cases of CAIS. The median age of the latter group was older at 14 yr (P10,P90:0.1,18). No cases of malignancy or carcinoma in situ were reported in the 121 cases of AIS where histology results were available. Biochemical endocrine investigations were reported to have been performed in a greater number of cases of PAIS than CAIS (98% vs. 48%). AR binding was abnormal in 44 of 51 (86%) and 40 of 113 (35%) cases of CAIS and PAIS, respectively. Zero binding was encountered in 29 of 43 (67%) and 1 of 55 (2%) cases of CAIS and PAIS, respectively. Mutational analysis of the AR gene, performed in 102 index cases was positive in 57 of 69 (83%) cases of CAIS and 12 of 43 (28%) cases of PAIS. In 24 of these cases, the mutation identified was novel. The mutations in PAIS cases were all missense, whereas in CAIS the mutations were more diverse. AR binding was only normal in 3 of 69 mutation-positive cases. In the PAIS group, mutation-positive cases had a significantly higher Kd and Bmax compared to the mutation negative cases. The clinical diagnosis of AIS can be confirmed in a significant number of cases by a combination of androgen-binding studies and mutational analysis. There is some correlation between the phenotypic features and the abnormalities discovered on mutational analysis of the AR gene, but there is a need to improve this further by developing optimal bioassays of AR function. The phenotypic heterogeneity among clinically diagnosed cases of AIS emphasizes the need for appropriate comprehensive evaluation of male under-masculinization.

Amino Acid Sequence↗
PubMed2000

Diagnosis of pacemaker lead infection using transoesophageal echocardiography: a case report.

INTRODUCTION: Vegetative lead infection is an uncommon complication of permanent pacemaker implantation. The diagnosis is difficult using conventional imaging methods. CLINICAL PICTURE: An elderly Indian woman with a history of diabetes mellitus developed Staphylococcus aureus infection after implementation of a permanent pacemaker. Following a non-diagnostic transthoracic echocardiogram, transoesophageal echocardiography was performed and showed a large vegetative mass attached to the pacemaker lead within the right atrium. TREATMENT: The pacemaker was removed and intravenous vancomycin administered for six weeks. OUTCOME: She was discharged well but demised two months later from a second episode of septicaemia. CONCLUSIONS: Pacemaker lead infection remains a challenging management problem. Transoesophageal echocardiography can facilitate its diagnosis.

Aged↗
PubMed2000

Hybrid cardiac revascularisation surgery.

Currently, 3 methods of myocardial revascularisation are available for the treatment of coronary artery disease: i) coronary artery bypass grafting (CABG); ii) percutaneous transluminal coronary angiography (PTCA), and iii) transmyocardial laser revascularisation (TMR). Until recently, these procedures were performed exclusive to one another. We report 2 cases of minimally invasive direct coronary artery bypass grafting with subsequent PTCA, and 1 case of staged PTCA followed by TMR performed at our institution. We discuss the role of hybrid procedures in the current era of treatment of ischaemic heart disease.

Aged↗
PubMed2000

Initial experience of radiofrequency catheter ablation of supraventricular tachycardia in paediatric patients.

INTRODUCTION: The management of supraventricular tachycardia (SVT) in paediatric patients until recently has frequently been pharmacologic therapy, but this approach suffers from the drawbacks of treatment failure, development of drug intolerance and/or side-effects. AIM: In keeping with recent advances in paediatric cardiology, we share our experience with radiofrequency catheter ablation as an alternative and definitive modality of therapy. MATERIALS AND METHOD: 4 young patients with recurrent SVT underwent electrophysiologic study followed by radiofrequency ablation of the accessory pathways. RESULTS: Resolution of symptoms was achieved in all patients and no major complication was encountered. CONCLUSIONS: The ability to ablate permanently the reentrant circuit responsible for SVT has now permitted cure by non-surgical means, and is an important alternative to drug therapy in the management of SVT in children.

Adolescent↗
PubMed2000

Biophysics and synchrotron radiation where the marriage fails. X-ray damage of lipid membranes and mesophases.

The call for brighter synchrotron X-radiation sources for use in structural biology research is barely audible as we enter the new millennium. Our brightest sources are already creating havoc when used at design specifications because of radiation damage. The time is long overdue to take stock of where we are and where we wish to go with regards to using existing sources and to designing new ones. The problem of radiation damage is particularly severe in studies involving kinetics and mechanism where cryotechniques are not always viable. Accordingly, we need to understand the very nature of radiation damage and to devise means for minimizing it. This is the thrust of the current study as applied to lipid membranes and mesophases. Here, we report on two very different types of radiation damage. One involves a dramatic phase transformation and the other a disordering of lamellar stacking. How beam energy and dose/rate affect damage is also discussed. The work highlights the nature of the damage process and the need for additional studies if we are to make most efficient use of an important resource, synchrotron radiation.

Biophysical Phenomena↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗