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Biomedical subjects

A Cheng

Publications and source records attributed to A Cheng.

At least 19 recordsLinked to original sources

Implications of hyperglycaemia and ethnicity in patients with acute coronary syndromes in New Zealand.

BACKGROUND: Admission blood glucose (ABG) is an independent predictor of death in patients with acute ST elevation myocardial infarction (STEMI). In New Zealand, mortality following myocardial infarction is disproportionally higher in Maori. Little information, however, exists concerning the predictive value of ABG in non-ST elevation acute coronary syndromes (NSTEACS) events or indeed if similar ethnic differences exist in outcome in this patient population. AIM: To assess the predictive value of ABG and ethnicity in individuals admitted with acute coronary syndromes (ACS) on mortality. METHODS: A retrospective analysis of hospital discharge diagnosis of all ACS between 1 January 1999 and 31 December 2002 at Waikato hospital, Hamilton, New Zealand. The primary outcome was all-cause mortality. RESULTS: There were 4408 episodes of ACS with 1091 (25%) due to STEMI. There were 806 (18%) deaths. The presence of diabetes mellitus (DM) or an elevated ABG, in the absence of a history of DM, was associated with poor patient outcome. Early mortality is seen in individuals presenting with STEMI. People in the highest glucose category were older, more likely to be Maori, had a higher percentage of people with diabetes and remained in hospital longer, regardless of ACS type, than those in the lowest glucose category. Diabetes was more common in Maori (33%) than in Europeans (17.5%); p < 0.001. Significant risk factors for mortality were age, gender, diabetes, ethnicity, glucose and STEMI. For each mmol/l increase in glucose there is a 4.3% increase risk of dying. Adjusting for age and gender, Maori have a much higher mortality than Europeans (RR 2.12; p < 0.00001) regardless of ACS type (STEMI or NSTEACS). CONCLUSIONS: Our study confirms the higher mortality following ACS, of Maori compared to New Zealanders of European origin. A raised ABG is a marker of this increased risk in all patients with ACS.

Aged↗

Construction of a primary RH panel of Italian ryegrass genome via UV-induced protoplast fusion.

Symmetric and asymmetric somatic hybrids were produced via protoplast fusion between common wheat ( TRITICUM AESTIVUM L.) cv. "Jinan 177" and Italian ryegrass ( LOLIUM MULTIFLORUM Lam.). The ryegrass without or with UV irradiation was used as a donor, providing a small amount of chromatin. In these somatic hybrids, most ryegrass chromosomes have been confirmed preferential elimination and the somatic hybrid calli and plants showed wheat-like morphology. Some of the hybrid lines were used for the analysis of distribution and heredity of donor DNA in the hybrid genome and the possibility of establishing a radiation hybrid (RH) panel of the ryegrass in the present experiment. These hybrids, subcultured for two and three years, retained the ryegrass DNA examined by RFLP and GISH analysis, respectively. Distribution of the ryegrass DNA in the wheat genomes of 20 single-cell individuals, randomly selected from hybrid cell lines produced, were analyzed by 21 ryegrass genome specific SSR markers. The average frequencies of molecular marker retention in symmetric hybrid lines (UV 0), as well as asymmetric hybrid lines from UV 30 s and 1 min were 10.88, 15.48 and 33.86, respectively. It was suggested that the UV dose increased the introgression of donor DNA into wheat genome. The ryegrass SSR fragments in most asymmetric hybrid cell lines remained stable over a period of 2 approximately 3 years. This revealed that those asymmetric somatic hybrids are suitable for the introgression of ryegrass DNA into wheat, and for RH panel and RH mapping.

Base Sequence↗

Ethnicity-specific prevalences of refractive errors vary in Asian children in neighbouring Malaysia and Singapore.

AIM: To compare the prevalences of refractive errors in Malay, Chinese and Indian children in Malaysia and Singapore. METHODS: Children aged 7-9 years from three schools in the Singapore Cohort study of the Risk factors for Myopia (n = 1962) and similarly aged children from a random cluster sample in the metropolitan Kuala Lumpur area in the Malaysia Refractive Error Study in Children (n = 1752) were compared. Cycloplegic autorefraction was conducted in both countries. RESULTS: The prevalence of myopia (spherical equivalent of at least -0.5 diopters (D) in either eye) was higher in Singapore Malays (22.1%) than in Malays in Malaysia (9.2%; 95% confidence interval (CI) 11.2 to 14.7; p<0.001). Similarly, Singapore Chinese (40.1%) had higher prevalences than Malaysian Chinese (30.9%; 95% CI 1.5 to 16.9). Singapore Indians had a higher prevalence (34.1%) than Malaysian Indians (12.5%; 95% CI 17.4 to 25.9). The multivariate odds ratio of astigmatism (cylinder at least 0.75 D in either eye) in Singapore Malays compared with Malaysian Malays was 3.47 (95% CI 2.79 to 4.32). Ethnicity-specific hyperopia rates did not differ in Singapore and Malaysia. CONCLUSION: The ethnicity-specific prevalences of myopia in Singapore Malays, Chinese and Indians are higher than those in Malaysian Malays, Chinese and Indians. As Malays, Chinese and Indians in Malaysia have genetic make-up similar to that of Malays, Chinese and Indians in Singapore, environmental factors may contribute to the higher myopia rates.

Asian People↗

Resistance development over 144 weeks in treatment-naive patients receiving tenofovir disoproxil fumarate or stavudine with lamivudine and efavirenz in Study 903.

OBJECTIVE: Study 903 was a 144-week, randomized, double-blind, active-controlled study of tenofovir disoproxil fumarate (TDF) therapy in treatment-naive HIV-1-infected patients. Patients received either TDF (n = 299) or stavudine (d4T) (n = 301) with lamivudine (3TC) and efavirenz (EFV). Resistance analyses were performed at baseline and at virological failure to determine the effects of baseline resistance and the patterns of resistance at virological failure. METHODS: Plasma HIV-1 from patients at baseline and at virological failure (>400 HIV-1 RNA copies/mL at week 144 or early discontinuation) was analysed phenotypically and by population sequencing. RESULTS: Sixteen per cent of patients were classified as having virological failure (47 on TDF and 49 on d4T; P = 0.91). Patients with non-B HIV-1 subtypes or baseline nucleoside reverse transcriptase inhibitor (NRTI)-associated mutations responded similarly to the overall population. Resistance to EFV (K103N and others) or 3TC (M184V) developed most frequently (8.3% and 5.8%, respectively) and similarly in the two arms. In the d4T arm, a variety of NRTI mutations developed: K65R (n = 2), L74V (n = 2), V75M (n = 1), and T69A + Y115H (n = 1). K65R developed in eight TDF patients (2.7%); in seven of these eight patients, within 48 weeks. All eight patients began new regimens with a protease inhibitor (PI) and NRTIs, including two patients who remained on TDF; five of the eight patients achieved HIV RNA <50 copies/mL in second-line therapy with the remaining patients having no follow-up or being nonadherent. CONCLUSIONS: Treatment of HIV-1 with TDF, 3TC and EFV was highly effective, with <3% of patients developing resistance to TDF over 144 weeks.

Adenine↗

The efficacy of a malarial antibody enzyme immunoassay for establishing the reinstatement status of blood donors potentially exposed to malaria.

BACKGROUND AND OBJECTIVES: The two key objectives of the study were, first, to evaluate the sensitivity and specificity of a recombinant antigen-based malarial enzyme-linked immunoassay (EIA) and, second, to estimate the risk associated with implementing this test with a shortened cellular component restriction period (6 months rather than the standard 12-36 months) for blood donors with a malarial risk exposure. MATERIALS AND METHODS: Blood donors were recruited into four distinct groups [non-exposed (control), malarial area 'visitors', 'residents' and 'previous infection') and screened by using the Newmarket malarial antibody EIA. Assay specificity was evaluated in unexposed blood donors, and sensitivity was determined in acute clinical samples. RESULTS: No parasitaemic donors were detected amongst 337 malarial 'visitors' who had returned from a malaria-endemic area less than 6 months previously, or for 402 'visitors' or 'residents' who had returned from a malaria-endemic area more than 6 months previously. The incidence of malarial antibodies within the exposed blood donor groups was 1.33% (10/751). In acute clinical non-donor samples, the Newmarket EIA detected 106/108 (98.1; 93.5-99.5%) 'film' positive Plasmodium falciparum infections and 12/12 (100, 75.7-100.0%) P. vivax infections. The estimated additional risk exposure of the proposed new strategy was one infectious P. falciparum donation per 175 years or 1 per 4.2 years for P. vivax. CONCLUSIONS: The study findings support the efficacy and safety of a targeted screening strategy combining antibody screening with a 6-month cellular component restriction period for donors with a declared malarial risk.

Algorithms↗

The dental implications of bisphosphonates and bone disease.

In 2002/2003 a number of patients presented to the South Australian Oral and Maxillofacial Surgery Unit with unusual non-healing extraction wounds of the jaws. All were middle-aged to elderly, medically compromised and on bisphosphonates for bone pathology. Review of the literature showed similar cases being reported in the North American oral and maxillofacial surgery literature. This paper reviews the role of bisphosphonates in the management of bone disease. There were 2.3 million prescriptions for bisphosphonates in Australia in 2003. This group of drugs is very useful in controlling bone pain and preventing pathologic fractures. However, in a small number of patients on bisphosphonates, intractable, painful, non-healing exposed bone occurs following dental extractions or denture irritation. Affected patients are usually, but not always, over 55 years, medically compromised and on the potent nitrogen containing bisphosphonates pamidronate (Aredia/Pamisol), alendronate (Fosamax) and zolendronate (Zometa) for non-osteoporotic bone disease. Currently, there is no simple, effective treatment and the painful exposed bone may persist for years. The main complications are marked weight loss from difficulty in eating and severe jaw and neck infections. Possible preventive and therapeutic strategies are presented although at this time there is no evidence of their effectiveness. Dentists must ask about bisphosphonate usage for bone disease when recording medical histories and take appropriate actions to avoid the development of this debilitating condition in their patients.

Adult↗

Intraocular pressure associations with refractive error and axial length in children.

AIM: To assess whether intraocular pressure (IOP) is associated with refractive error or axial length in children. METHODS: Of subjects from the Singapore Cohort Study of the Risk Factors for Myopia (SCORM), 636 Chinese children aged 9-11 years from two elementary schools underwent non-contact tonometry, cycloplegic autorefraction, and A-scan biometry during 2001. For analyses, refractive error was categorised into four groups; hypermetropia (spherical equivalent refraction (SE) > or = +1.0D), emmetropia (-0.5D<SE< +1.0D), low myopia (-3.0D<SE< or = -0.5D) and high myopia (SE< or = -3.0D). RESULTS: Of the 636 children examined, 50.6% were male. The mean IOP was 16.6 (SD 2.7) mm Hg. There were no significant IOP differences between low (mean IOP = 16.4 (2.8) mm Hg) or high myopes (16.7 (2.5) mm Hg) and emmetropes (16.7 (2.9) mm Hg), p = 0.57. IOP was not correlated with spherical equivalent refraction (Spearman correlation, r = 0.009) or axial length (r = 0.030). In regression analyses adjusting for diastolic blood pressure, neither spherical equivalent (regression coefficient = 0.014) nor axial length (regression coefficient = 0.027) were significantly associated with IOP. CONCLUSION: These findings do not support an association between IOP and refractive error or axial length in children. This questions postulated roles of IOP in the pathogenesis of myopia.

Biometry↗

Duplex ultrasonography after total hip or knee arthroplasty.

We prospectively studied all patients admitted for total hip (THR) or knee (TKR) arthroplasty from July 2000 to February 2001. No pharmacological anticoagulation was given. All patients received a standardized postoperative rehabilitation regimen. Forty-six patients with known risk factors for deep vein thrombosis (DVT) were excluded. Eighty patients were studied (22 THR, 58 TKR; 55 women, 25 men). Mean age was 68 (30-90) years. Duplex ultrasonography on both lower limbs was performed on days 5-7 postoperatively. Location and extent of any thrombus were documented. In patients with distal DVT, a follow-up scan was done on days 10-14. If proximal propagation was observed, patients received full anticoagulation. If no propagation was detected, the distal thrombus was considered stable and clinical observation was continued. In the THR group, 1/22 and in the TKR group 9/58 were found to have distal DVT. All were asymptomatic. On follow-up scanning, none showed proximal propagation. All patients were followed up for at least 18 months, and none showed postthrombotic symptoms. Isolated distal DVT in "low-risk" Chinese patients after THR or TKR is not uncommon. Clinically they are usually "silent." If routine perioperative pharmacologic antithrombotic prophylaxis is not practiced, monitoring with duplex ultrasonography may need to be considered.

Adult↗

Homocysteine, folate and vitamin B12 as risk factors for acute myocardial infarction in a Southeast Asian population.

INTRODUCTION: Hyperhomocysteinaemia is an emerging risk factor for coronary artery disease (CAD) and most studies done to date are in Caucasian populations. We aimed to determine whether hyperhomocysteinaemia is a risk factor for acute myocardial infarction (AMI) in a Southeast Asian population comprising different ethnic groups and relate it to the traditional risk factors and plasma vitamin B12 and folate levels. MATERIALS AND METHODS: This was a case-control study comprising 168 AMI patients and 141 controls with a median age of 55 years (range, 27 to 77 years), living in Singapore. Homocysteine was measured by fluorescence polarisation immunoassay and vitamin B12 and folate were measured by electrochemiluminescence immunoassay. Logistic regression analysis was use to test the association of homocysteine, vitamin B12 and folate with the occurrence of AMI. The study was approved by the Tan Tock Seng Ethics Committee. RESULTS: We found that the odds of having AMI was higher for subjects with hypertension, smoking habit, lower plasma folate and vitamin B12 levels and non-Chinese ethnic group. On the other hand, plasma homocysteine level was not significantly associated with AMI. The baseline levels of plasma total homocysteine in both AMI patients and controls were higher than other studies (median values between 12 and 14 umol/L). CONCLUSION: In our population, plasma total homocysteine levels were not associated with AMI but low plasma levels of folate and vitamin B12 were independently associated.

Adult↗

A preliminary study of the utility of combined cardiac markers in the evaluation of patients presenting early with suspected acute coronary syndrome.

OBJECTIVE: The aim of the study was to investigate and compare the usefulness and accuracy of various cardiac markers [troponin I, creatine kinase MB (CKMB) mass, creatine kinase (CK), CKMB activity] to aid early diagnosis of myocardial infarction. We also examined the ability of the various cardiac markers to prognosticate future adverse cardiac events. MATERIALS AND METHODS: Patients admitted within 8 hours of maximal chest pain suggestive of acute coronary syndrome with non-diagnostic electrocardiograms were recruited. Blood samples were obtained on admission to the wards and repeated 4 hours later. These results were later correlated to the final hospital discharge diagnosis. RESULTS: The 37 patients in the study were a high-risk population with over 50% presenting with a Thrombolysis in Myocardial Infarction (TIMI) risk score of greater or equal to 3. Myoglobin was the most sensitive marker (100% sensitivity) in early prediction of patients who were subsequently diagnosed to have a myocardial infarction. Patients with an elevated troponin I level but normal CK and myoglobin levels had a significantly higher risk of developing a major adverse clinical event (MACE) within 3 months of the initial presentation. CONCLUSION: Myoglobin is the most sensitive marker when compared to CK, CKMB and troponin I for diagnosing patients presenting early with chest pain and a non-diagnostic electrocardiogram and who subsequently develop either a ST-elevation myocardial infarction or non-ST elevation myocardial infarction. Patients with an elevated troponin I level but normal CK and myoglobin levels are at higher risk of an adverse clinical event.

Adult↗

TYK2 and JAK2 are substrates of protein-tyrosine phosphatase 1B.

The reversible tyrosine phosphorylation of proteins, modulated by the coordinated actions of protein-tyrosine kinases and protein-tyrosine phosphatases (PTPs), regulates the cellular response to a wide variety of stimuli. It is established that protein kinases possess discrete sets of substrates and that substrate recognition is often dictated by the presence of consensus phosphorylation sites. Here, we have extended this concept to the PTPs and demonstrated that (E/D)-pY-pY-(R/K) is a consensus substrate recognition motif for PTP1B. We have shown that JAK2 and TYK2 are substrates of PTP1B and that the substrate recognition site within theses kinases is similar to the site of dephosphorylation previously identified within the insulin receptor. A substrate-trapping mutant of PTP1B formed a stable interaction with JAK2 and TYK2 in response to interferon stimulation. Expression of wild type or substrate-trapping mutant PTP1B inhibited interferon-dependent transcriptional activation. Finally, mouse embryo fibroblasts deficient in PTP1B displayed subtle changes in tyrosine phosphorylation, including hyperphosphorylation of JAK2. The closely related JAK family member, JAK1, which does not match the consensus dephosphorylation site, was not recognized as a substrate. These data illustrate that PTP1B may be an important physiological regulator of cytokine signaling and that it may be possible to derive consensus substrate recognition motifs for other members of the PTP family, which may then be used to predict novel physiological substrates.

Amino Acid Sequence↗

The landing of the NEAR-Shoemaker spacecraft on asteroid 433 Eros.

The NEAR-Shoemaker spacecraft was designed to provide a comprehensive characterization of the S-type asteroid 433 Eros (refs 1,2,3), an irregularly shaped body with approximate dimensions of 34 x 13 x 13 km. Following the completion of its year-long investigation, the mission was terminated with a controlled descent to its surface, in order to provide extremely high resolution images. Here we report the results of the descent on 12 February 2001, during which 70 images were obtained. The landing area is marked by a paucity of small craters and an abundance of 'ejecta blocks'. The properties and distribution of ejecta blocks are discussed in a companion paper. The last sequence of images reveals a transition from the blocky surface to a smooth area, which we interpret as a 'pond'. Properties of the 'ponds' are discussed in a second companion paper. The closest image, from an altitude of 129 m, shows the interior of a 100-m-diameter crater at 1-cm resolution.

Journal Article↗

p38 MAP kinase mediates nitric oxide-induced apoptosis of neural progenitor cells.

Neural progenitor cells (NPC) can proliferate, differentiate into neurons or glial cells, or undergo a form of programmed cell death called apoptosis. Although death of NPC occurs during development of the nervous system and in the adult, the underlying mechanisms are unknown. Here we show that nitric oxide (NO) can induce death of C17.2 NPC by a mechanism requiring activation of p38 MAP kinase, poly(ADP-ribose) polymerase, and caspase-3. Nitric oxide causes release of cytochrome c from mitochondria, and Bcl-2 protects the neural progenitor cells against nitric oxide-induced death, consistent with a pivotal role for mitochondrial changes in controlling the cell death process. Inhibition of p38 MAP kinase by SB203580 abolished NO-induced cell death, cytochrome c release, and activation of caspase-3, indicating that p38 activation serves as an upstream mediator in the cell death process. The anti-apoptotic protein Bcl-2 protected NPC against nitric oxide-induced apoptosis and suppressed activation of p38 MAP kinase. The ability of nitric oxide to trigger death of NPC by a mechanism involving p38 MAP kinase suggests that this diffusible gas may regulate NPC fate in physiological and pathological settings in which NO is produced.

Animals↗

Current indoor allergen levels of fungi and cats, but not house dust mites, influence allergy and asthma in adults with high dust mite exposure.

We assessed the influence of current indoor levels of fungi, house dust mite allergen (Der p 1), and cat allergen (Fel d 1) on sensitization and asthma in adults. A total of 485 adults answered a questionnaire and had skin prick tests and lung function tests. Dust and air samples were collected from their bedrooms. The dust was analyzed for Der p 1, Fel d 1, and fungal biomass (ergosterol). Fungal propagules were measured in air samples. Current asthma was defined as having wheezed during the past 12 mo plus bronchial hyperreactivity (BHR) to methacholine. High exposure to total airborne fungi was associated with increased BHR, but perhaps paradoxically with a lower risk of being sensitized to fungi. Ergosterol levels in floor dust were a risk factor both for being sensitized to fungi and having wheezed within the last year. High Fel d 1 levels in floor dust were found to increase the risk of being sensitized to cats and in beds to increase the risk of current asthma. Although Der p 1 levels in homes were high, people exposed to high Der p 1 levels in floor dust were less likely to be sensitized to house dust mites or to have wheezed within the past year. Current indoor levels of fungi and Fel d 1, but not Der p 1, influenced sensitization and asthma in adults with high dust mite exposure.

Adult↗

Attenuation of adhesion-dependent signaling and cell spreading in transformed fibroblasts lacking protein tyrosine phosphatase-1B.

Previous biochemical evidence has yielded conflicting models for the role of protein tyrosine phosphatase-1B (PTP-1B) in the regulation of integrin signaling. Thus, to establish the physiological relevance for such a role, we employed a genetic approach by generating embryonic fibroblasts from PTP-1B knockout mice. Both primary fibroblasts and their derived cell lines were used in this study. Immortalization of wild-type primary cells with the SV40 Large T antigen resulted in a dramatic increase in the endogenous expression of PTP-1B, suggesting a role during transformation. Moreover, the absence of PTP-1B in the transformed cell lines led to a more pronounced effect on different pathways of fibronectin-mediated signaling compared with the untransformed state. Specifically, p130(Cas) phosphorylation, Erk activation as well as cell spreading were delayed in PTP-1B-deficient cells, compared with their wild-type counterparts. Interestingly, this attenuation in integrin-mediated events closely resembles that of Src-deficient fibroblasts. Indeed, PTP-1B deficient, transformed fibroblasts held in suspension do exhibit a hyperphosphorylation of the inhibitory site (Tyr-527) of Src, compared with their wild-type counterparts. These results establish PTP-1B as a positive physiological regulator of integrin signaling in transformed cells, acting upstream of Src Tyr-527 dephosphorylation that leads to several adhesion-dependent events.

Animals↗

Imaging of small-scale features on 433 Eros from NEAR: evidence for a complex regolith.

On 25 October 2000, the Near Earth Asteroid Rendevous (NEAR)-Shoemaker spacecraft executed a low-altitude flyover of asteroid 433 Eros, making it possible to image the surface at a resolution of about 1 meter per pixel. The images reveal an evolved surface distinguished by an abundance of ejecta blocks, a dearth of small craters, and smooth material infilling some topographic lows. The subdued appearance of craters of different diameters and the variety of blocks and different degrees of their burial suggest that ejecta from several impact events blanketed the region imaged at closest approach and led to the building up of a substantial and complex regolith consisting of fine materials and abundant meter-sized blocks.

Journal Article↗