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Biomedical subjects

A Cheng

Publications and source records attributed to A Cheng.

At least 91 records · Page 5Linked to original sources
PubMed1997

Evidence for DNA-PK-dependent and -independent DNA double-strand break repair pathways in mammalian cells as a function of the cell cycle.

Mice homozygous for the scid (severe combined immune deficiency) mutation are defective in the repair of DNA double-strand breaks (DSBs) and are consequently very X-ray sensitive and defective in the lymphoid V(D)J recombination process. Recently, a strong candidate for the scid gene has been identified as the catalytic subunit of the DNA-dependent protein kinase (DNA-PK) complex. Here, we show that the activity of the DNA-PK complex is regulated in a cell cycle-dependent manner, with peaks of activity found at the G1/early S phase and again at the G2 phase in wild-type cells. Interestingly, only the deficit of the G1/early S phase DNA-PK activity correlated with an increased hypersensitivity to X-irradiation and a DNA DSB repair deficit in synchronized scid pre-B cells. Finally, we demonstrate that the DNA-PK activity found at the G2 phase may be required for exit from a DNA damage-induced G2 checkpoint arrest. These observations suggest the presence of two pathways (DNA-PK-dependent and -independent) of illegitimate mammalian DNA DSB repair and two distinct roles (DNA DSB repair and G2 checkpoint traversal) for DNA-PK in the cellular response to ionizing radiation.

Animals↗
PubMed1997

Correlation between retinal fluorescein angiography and blood viscosity and other factors in patients with primary open angle glaucoma.

OBJECTIVE: To investigate the correlation among retinal fluorescein angiography, blood viscosity, and other factors in patients with open angle glaucoma (POAG). METHODS: Multiple step regression analysis was made to investigate the correlation between each of the following blood vessel filling times: the arm-choroid (A-CT), arm-retinal artery (A-AT), and retinal artery-venous (A-VT) of the fundus fluorescein angiography (FFA) in 122 eyes with POAG and each of the following related factors in hemorrheology: whole blood apparent viscosity at low, medium and high shear rates, plasma viscosity and hematocrit. Also, the same analysis was applied to investigate the correlation between each of the A-AT, A-VT of the FFA in 70 eyes with POAG and the following factors: systolic blood pressure, diastolic blood pressure, age and whole blood apparent viscosity at low shear rate. RESULTS: The whole blood apparent viscosity at low shear rate was closely related to A-CT and A-AT, while hematocrit was closely related to A-VT of the FFA. The whole blood apparent viscosity at low shear rate and age, especially the whole blood apparent viscosity, was closely related to A-AT, A-VT of the FFA. CONCLUSION: Blood viscosity can affect the filling times of the FFA in POAG.

Blood Viscosity↗
PubMed1997

[A preliminary report on clinical application of biopoly ester ligament].

Sixty-one cases of fracture or dislocation were treated with France-made biopolyester ligament. They consisted of 18 cases of fracture of patella, 13 cases of fracture of olecranon, 8 cases of fracture of distal clavicle, 10 cases of dislocation of acromino-clavicular joint, 6 cases of separation of lower tibio-fibular joint, 3 cases of rapture of cruciate ligament and 3 cases of fracture of upper third of ulna with dislolcation of radial head. The follow-up period lasted from 3 to 12 months with an average of 7.3 months. The result showed that of the 56 follow-up cases, 49 were excellent and 7 were satisfactory. There was no redisplacement occured in this group. The Biopolyester ligament was believed to be a good and safe material for fractures or dislocations and was of good strength of extension and easy to use.

Adolescent↗
PubMed1996

Prospective clinical evaluation of an electronic portal imaging device.

PURPOSE: To determine whether the clinical implementation of an electronic portal imaging device can improve the precision of daily external beam radiotherapy. METHODS AND MATERIALS: In 1991, an electronic portal imaging device was installed on a dual energy linear accelerator in our clinic. After training the radiotherapy technologists in the acquisition and evaluation of portal images, we performed a randomized study to determine whether online observation, interruption, and intervention would result in more precise daily setup. The patients were randomized to one of two groups: those whose treatments were actively monitored by the radiotherapy technologists and those that were imaged but not monitored. The treating technologists were instructed to correct the following treatment errors: (a) field placement error (FPE) > 1 cm; (b) incorrect block; (c) incorrect collimator setting; (d) absent customized block. Time of treatment delivery was recorded by our patient tracking and billing computers and compared to a matched set of patients not participating in the study. After the patients radiation therapy course was completed, an offline analysis of the patient setup error was planned. RESULTS: Thirty-two patients were treated to 34 anatomical sites in this study. In 893 treatment sessions, 1,873 fields were treated (1,089 fields monitored and 794 fields unmonitored). Ninety percent of the treated fields had at least one image stored for offline analysis. Eighty-seven percent of these images were analyzed offline. Of the 1,011 fields imaged in the monitored arm, only 14 (1.4%) had an intervention recorded by the technologist. Despite infrequent online intervention, offline analysis demonstrated that the incidence of FPE > 10 mm in the monitored and unmonitored groups was 56 out of 881 (6.1%) and 95 out of 595 (11.2%), respectively; p < 0.01. A significant reduction in the incidence of FPE > 10 mm was confined to the pelvic fields. The time to treat patients in this study was 10.78 min (monitored) and 10.10 min (unmonitored). Features that were identified that prevented the technologists from recognizing more errors online include poor image quality inherent to the portal imaging device used in this study, artifacts on the portal images related to table supports, and small field size lacking sufficient anatomical detail to detect FPEs. Furthermore, tools to objectively evaluate a portal image for the presence of field placement error were lacking. These include magnification factor corrections between the simulation of portal image, online measurement tools, image enhancement tools, and image registration algorithms. CONCLUSION: The use of an electronic portal imaging device in our clinic has been implemented without a significant increase in patient treatment time. Online intervention and correction of patient positioning occurred rarely, despite FPEs of > 10 mm being present in more than 10% of the treated fields. A significant reduction in FPEs exceeding 10 mm was made in the group of patients receiving pelvic radiotherapy. It is likely that this improvement was made secondarily to a decrease in systematic error and not because of online interventions. More significant improvements in portal image quality and the availability of online image registration tools are required before substantial improvements can be made in patient positioning with online portal imaging.

Brain Neoplasms↗
PubMed1996

Free radical mediated x-ray damage of model membranes.

The damaging effects of synchrotron-derived x rays on aqueous phospholipid dispersions have been evaluated. The effect of degree of lipid hydration, phospholipid chemical structure, mesophase identity, aqueous medium composition, and incident flux on the severity and progress of damage was quantified using time-resolved x-ray diffraction and chromatographic analysis of damage products. Electron spin resonance measurements of spin-trapped intermediates generated during irradiation suggest a free radical-mediated process. Surprisingly, radiation damage effects revealed by x-ray diffraction were imperceptible when the lamellar phases were prepared under water-stressed conditions, despite the fact that x-ray-induced chemical breakdown of the lipid occurred regardless of hydration level. Of the fully hydrated lipid systems studied, saturated diacyl-phosphatidylcholines were most sensitive to radiation damage compared to the ester- and ether-linked phosphatidylethanolamines and the ether-linked phosphatidylcholines. The inclusion of buffers or inorganic salts in the dispersing medium had only a minor effect in reducing damage development. A small inverse dose-rate effect was found when the x-ray beam intensity was changed 15-fold. These results contribute to our understanding of the mechanism of radiation damage, to our appreciation of the importance of monitoring both structure and composition when evaluating biomaterials radiation sensitivity, and to the development of strategies for eliminating or reducing the severity of damage due to an increasingly important source of x rays, synchrotron radiation. Because damage is shown to be free radical mediated, these results have an important bearing on age-related accumulation of free radicals in cells and how these might compromise membrane integrity, culminating in cell death.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1996

The risks of hip fracture in older people from private homes and institutions.

This study aimed to determine whether the incidence of hip fracture is greater among those living in institutions compared with those living in private homes. Over two and a half years of surveillance, 1832 hip fractures were identified, of which 58% were sustained by those living in private homes and 42% by those living in institutions. The risks of hip fracture, unadjusted for age and sex, were 10.5 times greater for those living in institutions compared with those living in private homes. After adjusting for age and sex, these greatly increased risks were maintained, although for both men and women the risks decreased with age, such that at ages over 90 years the risks were not significantly different. Given these findings, hip fracture prevention strategies that focus particularly on individuals within institutions are highly commended.

Aged↗
PubMed1996

Systematic verification of a three-dimensional electron beam dose calculation algorithm.

A three-dimensional electron beam dose calculation algorithm implemented on a commercial radiotherapy treatment planning system is described. The calculation is based on the M. D. Anderson Hospital (M.D.A.H.) pencil beam model, which uses the Fermi-Eyges theory of thick-target multiple Coulomb scattering. To establish the calculation algorithm's accuracy as well as its limitations, it was systematically and extensively tested and evaluated against a set of benchmark measurements. Various levels of dose and spatial tolerances were used to validate the calculation quantitatively. Results are presented in terms of the percentage of data points meeting a specific tolerance level. The algorithm's ability to accurately simulate commonly used clinical setup geometries, including standard or extended SSDs, blocked fields, irregular surfaces, and heterogeneities, is demonstrated. Regions of disagreement between calculations and measurements are also shown. The clinical implication of such disagreements is addressed, and the algorithmic assumptions involved are discussed.

Algorithms↗
PubMed1996

Telecardiology: supporting the decision-making process in general practice.

To assess the initial phase of a telecardiology diagnostic service for general practitioners (GPs), we provided 93 GPs in 26 health centres with direct telephone access to a cardiologist, and equipped them with hand-held, automatic standard 12-lead electrocardiogram (ECG) transmitters for on-line cardiac consultations and ECG interpretation in their daily practice. Clinical details, reason for consultation and the ECG signal were transmitted from the GPs' practices or the patients' homes. A consultation followed and a full report, including ECG print-out, was then sent to the GP. During an 18-month study period, 2563 consultations were carried out. The system allowed the identification of 479 patients (19%) with urgent cardiac problems and the remaining 2084 (81%) in whom admission or outpatient investigation was unnecessary. Following the study, we distributed a questionnaire asking the GPs to rate the quality, define the use and consider the benefit of the service to their daily practice. We conclude that a telecardiology diagnosis and ECG interpretation service is simple, reliable and efficacious in routine primary care. It offers instant access to cardiac assessment and supports the decision-making process of GPs. A preliminary cost comparison with a conventional referral indicated that a teleconsultation was substantially cheaper. We expect that the future incorporation of teleechocardiography would expand the scope of telecardiology even further and allow comprehensive cardiology consultations.

Cardiology↗
PubMed1995

Fletcher Challenge-University of Auckland Heart & Health Study: design and baseline findings.

AIMS: The aims of this prospective observational study are to determine the relationship of sociodemographic factors, psychological factors and several factors measured in blood, with the risk of coronary heart disease (CHD) in a New Zealand population. METHODS: Participants were recruited from two sources: employees of the Fletcher Challenge Group and individuals listed on the general electoral roll for the Auckland region. Baseline and follow up risk factor data were obtained from a questionnaire, blood samples and a simple physical examination. Outcome data on deaths and hospitalisations due to coronary heart disease will be obtained primarily through linkage of participant identifiers to data collected nationally by the New Zealand Health Information Service. RESULTS: A total of 10,529 individuals agreed to participate (8011 from Fletcher Challenge and 2518 from the electoral roll), representing a response rate of 74%. Within the study population, there was a broad distribution of sociodemographic characteristics including ethnicity-10% of participants were Maori and 5% were of Pacific Islands origin. There was also wide heterogeneity of coronary heart disease risk as judged from the distributions of established risk factors at baseline-5% of participants had evidence of existing coronary heart disease, a quarter were current smokers, a sixth were nondrinkers, almost a half were overweight, a fifth had blood pressure > or = 150/95 mmHg or were receiving antihypertensive treatment and a sixth had cholesterol levels > or = 6.5 mmol/L. CONCLUSIONS: This is the first, large scale prospective observational study of the determinants of coronary heart disease in a New Zealand population. The study participants represent a broad cross section of society, with wide variation in sociodemographic characteristics and coronary heart disease risk. Initial results concerning the relationships of primary interest should be available within 5 years when sufficient coronary heart disease events have been documented to allow reliable analyses.

Adult↗
PubMed1995

Tissue- and species-specific expression of sp56, a mouse sperm fertilization protein.

Mouse sperm recognize and bind to ZP3, one of three glycoproteins in the egg's zona pellucida. A mouse sperm protein, sp56, was identified that has the characteristics expected of the sperm protein responsible for recognition of ZP3. The complementary DNA encoding sp56 was isolated, and its primary sequence indicates that sp56 is a member of a superfamily of protein receptors. It was shown that sp56 expression is restricted to mouse spermatids and that the presence or absence of sp56 on sperm from different species accounts for species specificity of sperm-egg recognition in mice.

Amino Acid Sequence↗
PubMed1995

Alteration in nicotine binding sites in Parkinson's disease, Lewy body dementia and Alzheimer's disease: possible index of early neuropathology.

High-affinity nicotine binding, considered to primarily reflect the presence of CNS alpha 4 beta 2 nicotinic receptor subunits, was examined autoradiographically in brain regions most severely affected by Alzheimer and Parkinson types of pathology. In the midbrain, the high density of binding associated with the pars compacta of the substantia nigra was extensively reduced (65-75%, particularly in the lateral portion) in both Lewy body dementia and Parkinson's disease. Since loss of dopaminergic neurons in Lewy body dementia was only moderate (40%), loss or down-regulation of the nicotinic receptor may precede degeneration of dopaminergic neurons in this region. In the dorsolateral tegmentum, where diffuse cholinergic perikarya are located, nicotine binding was highly significantly decreased in both Lewy body dementia and Parkinson's disease with almost no overlap between the normal and disease groups, indicative of a major pathological involvement in or around the pedunculopontine cholinergic neurons. In the hippocampus, binding was decreased around the granular layer in Lewy body dementia and Alzheimer's disease, although unchanged in the stratum lacunosum moleculare, where binding was relatively higher. Dense bands of receptor binding in the presubiculum and parahippocampal gyrus--areas of highest binding in human cortex--were diminished in Alzheimer's disease but not Lewy body dementia. In temporal neocortex there were reductions in Alzheimer's disease throughout the cortical layers but in Lewy body dementia only in lower layers, in which Lewy bodies are concentrated. Abnormalities of the nicotinic receptor in the diseases examined appear to be closely associated with primary histopathological changes: dopaminergic cell loss in Parkinson's disease and Lewy body dementia, amyloid plaques and tangles in subicular and entorhinal areas in Alzheimer's disease. Loss or down-regulation of the receptor may precede neurodegeneration.

Acetylcholinesterase↗
PubMed1995

Kinetics of lipid phase changes.

In the past two years, the kinetics of transitions involving the assorted lamellar and inverted hexagonal and cubic phases in bulk hydrated lipid systems have been established using a variety of physical techniques. In several cases, the kinetic data have lead to a transition mechanisms being deciphered.

Crystallization↗
PubMed1995

Immuno-colloidal gold labeled surface replica, and its application to detect sp56, the egg recognition and binding protein, on the mouse spermatozoon.

Using immuno-colloidal gold surface replicas (IGSR), we developed a method to demonstrate surface antigens in a whole view of a cell at the EM level. In this study, a monoclonal antibody (MAB) 7C5 directed against sp56, which is a mouse sperm protein (M(r) = 56,000 daltons) and has specific affinity for the zona pellucida, was used as primary antibody. Fixed mouse spermatozoa were incubated with primary antibody and colloidal gold-labeled secondary antibody on a slide glass. Used gold particles were 10, 20 or 30 nm in diameter. The spermatozoa were then critical point dried, and replicated with platinum and carbon. Replicas were examined with a transmission EM. The result suggests that sp56 is located on the outer surface of the plasma membrane covering approximately 2/3 of dorsal edge of the sperm head, but it is virtually absent in the tapered apical tip. When 10 and 20 nm colloidal particles were used, about 500 particles were observed on one side of the flat sperm head. Although the large 30 nm particles were easily recognized in low magnification figures, the attached number on the sperm head was generally lower than the number of 10 or 20 nm particles observed. By this method, we could effectively demonstrate the localization of a surface antigen in a wide cell view with clear landmarks.

Animals↗
PubMed1995

Scrub typhus pneumonitis with delayed resolution.

A 35-year-old lady was admitted to hospital with fever and dry cough. Chest radiograph showed bilateral basal infiltrate. Her Weil-Felix test was strongly positive (OX-K > 1:160) and her fever came down with intravenous tetracycline. There was no improvement in the lung shadow and spirometry showed a severe restrictive defect. Open lung biopsy confirmed the diagnosis of interstitial pneumonitis. CT of thorax 6 months after presentation showed partial resolution of the interstitial shadow.

Adult↗