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Biomedical subjects

S Tong

Publications and source records attributed to S Tong.

At least 19 recordsLinked to original sources
PubMed2002

Regulation of fusion activity by the cytoplasmic domain of a paramyxovirus F protein.

SER virus is a member of the family Paramyxoviridae, genus Rubulavirus, which has been isolated from pigs. It is very closely related to SV5 virus serologically, in protein profile, and in nucleotide sequence. However, unlike SV5, SER induces minimal syncytium formation in infected CV-1 or BHK cells. Fluorescence transfer experiments between labeled erythrocytes and infected MDBK cells revealed that SER also induces hemifusion and pore formation with reduced efficiency. The virion polypeptide profiles of SER and SV5 are very similar, except that the SER F1 subunit shows an apparent molecular weight that is about 2 kDa higher than that of SV5. Comparison of the deduced amino acid sequences revealed the SER F (551 aa) to be longer than SV5 F (529 aa) by 22 residues in the cytoplasmic tail (CT) domain. The HN and M gene sequences of the viruses were found to be very similar. The SER F showed minimal fusion activity when coexpressed with either SV5 or SER HN. In contrast, SV5 F was highly fusogenic when coexpressed with either HN protein, indicating that the restricted fusion capacity of SER virus is a property of its F protein. Truncation in the CT of SER F by 22 residues completely rescued its ability to cause syncytium formation, whereas other truncations rescued syncytium formation partially. These results demonstrate that an elongated CT of a paramyxovirus F protein suppresses its membrane fusion activity.

Animals↗
PubMed2002

Myopathy with lobulated muscle fibers: evidence for heterogeneous etiology and clinical presentation.

The clinico-pathological features of 17 patients displaying a myopathy with lobulated (trabeculated) fibers are reported. All these patients had a limb girdle phenotype and at least 20% of lobulated fibers in their muscle biopsies. There were ten females and seven males. The onset of symptoms ranged from 2 to 55 years (mean 24). The average age at the time of muscle biopsy was 39 (range 3-63). Interestingly, in six patients, high prevalence of lobulated fibers was observed at the second biopsy only, performed on average 11 years after the first or in another muscle. Six patients had a suggestively positive family history. Facial weakness was noted in two patients (genetic study confirmed FSH dystrophy). The course and the severity of weakness varied from one patient to another. Immunohistochemistry and Western blot analyses revealed one Duchenne carrier, one alpha-sarcoglycanopathy, no dysferlinopathy and four calpain deficiencies (including one patient with FSH dystrophy), but SSCP revealed mutation in the calpain gene in only one of the patients. These results show that (1) myopathies with lobulated fibers are clinically and genetically heterogeneous, (2) lack of calpain expression by Western blot analysis is not always associated with null mutation, (3) a molecular diagnosis is made in less than 40% of myopathy with lobulated fibers, (4) when observed, lobulated fibers are most prominent in proximal muscles and require time to appear.

Adolescent↗
PubMed2002

Maternal and foetal activin A levels: associations with normal and abnormal labour.

In pregnancy the feto-placental unit is the major source of activin A. However, the role(s) of activin A in late pregnancy remain uncertain and controversial. In particular, whether activin A levels alter in association with labour is unclear. In a cross-sectional cohort study, maternal serum samples were collected from women at term prior to elective Caesarean section (n=11), during labour prior to a spontaneous vaginal delivery (n=31), an instrumental vaginal delivery (n=16) or an emergent Caesarean section (n=7). Umbilical artery blood samples were collected from 75 pregnancies, after an elective Caesarean section (n=9), a normal vaginal delivery (n=37), an instrumental vaginal delivery (n=15) or an emergent Caesarean section (n=14). Levels of activin A were measured and compared according to modes of delivery. Maternal, but not foetal, serum activin A was increased significantly in women who were delivered by an intrapartum Caesarean section compared to other modes of delivery. Foetal, but not maternal, serum activin A was significantly correlated with umbilical artery pH. Maternal serum activin A is increased in women undergoing an intrapartum Caesarean section compared to either a vaginal delivery or an elective Caesarean section. The mechanism(s) underlying this observation are not clear.

Activins↗
PubMed2002

Climate variability and Ross River virus transmission.

OBJECTIVES: (1) To examine the feasibility to link climate data with monthly incidence of Ross River virus (RRv). (2) To assess the impact of climate variability on the RRv transmission. DESIGN: An ecological time series analysis was performed on the data collected between 1985 to 1996 in Queensland, Australia. METHODS: Information on the notified RRv cases was obtained from the Queensland Department of Health. Climate and population data were supplied by the Australian Bureau of Meteorology and the Australian Bureau of Statistics, respectively. Spearman's rank correlation analyses were performed to examine the relation between climate variability and the monthly incidence of notified RRv infections. The autoregressive integrated moving average (ARIMA) model was used to perform a time series analysis. As maximum and minimum temperatures were highly correlated with each other (r(s)=0.75), two separate models were developed. RESULTS: For the eight major cities in Queensland, the climate-RRv correlation coefficients were in the range of 0.12 to 0.52 for maximum and minimum temperatures, -0.10 to 0.46 for rainfall, and 0.11 to 0.52 for relative humidity and high tide. For the whole State, rainfall (partial regression coefficient: 0.017 (95% confidence intervals 0.009 to 0.025) in Model I and 0.018 (0.010 to 0.026) in Model II), and high tidal level (0.030 (0.006 to 0.054) in Model I and 0.029 (0.005 to 0.053) in Model II) seemed to have played significant parts in the transmission of RRv in Queensland. Maximum temperature was also marginally significantly associated with the incidence of RRv infection. CONCLUSION: Rainfall, temperature, and tidal levels may be important environmental determinants in the transmission cycles of RRv disease.

Alphavirus Infections↗
PubMed2002

Management of spinal trauma in 69 cats.

This study sought to evaluate a series of clinical and radiological findings on spinal trauma in cats and the outcome that emerged from conservative or surgical treatment using 2 types of spinal stapling: stabilization using a Steinmann pin and coated polypropylene. Case records were reviewed for their diagnostic approaches on the basis of physical and neurological conditions, and concurrent disorders in addition to spinal trauma. Radiological examinations of the vertebral column were carried out using survey radiography, myelography and epidurography. All cases were classified according to etiopathogenesis of the disease. Surgical treatment consisted of decompression (laminectomy, hemilaminectomy and durotomy), or decompression with stabilization which was performed by one of two methods. The first one was the employment of translaminar stapling at the base of a spinous process and the other involved spinal stapling at the spinous process. The spinal lesions were identified as cervical (n = 2), thoracic (n = 35), lumbar (n = 22), sacral and caudal (n = 10). While 19 out of 30 conservatively managed cases recovered, the rest had persistent residual paresis and ataxia. Complete recovery was seen in 4 cats that underwent hemilaminectomy and 3 subjected to laminectomy. Partial recovery was observed in 5 cases involving laminectomy; however, there was no improvement observed in another 2 cases. Each animal was followed for at least a 3-month period to evaluate the clinical assessment of the results following treatment. The results of conservative and operative management of spinal trauma indicated that the type and degree of spinal cord degradation strongly influenced any prognosis. The results emerging from decompressive procedures seemed satisfactory for those cases where instability was not an issue. Both stabilization techniques were not ideal in terms of their methodological versatility or regarding weaknesses of bone structure observed in intra- and postoperative periods. However, translaminar stapling at the base of a spinous process was deemed to be the superior technique.

Animals↗
PubMed2001

The discovery of sulfonylated dipeptides as potent VLA-4 antagonists.

Directed screening of a carboxylic acid-containing combinatorial library led to the discovery of potent inhibitors of the integrin VLA-4. Subsequent optimization by solid-phase synthesis afforded a series of sulfonylated dipeptide inhibitors with structural components that when combined in a single hybrid molecule gave a sub-nanomolar inhibitor as a lead for medicinal chemistry. Preliminary metabolic studies led to the discovery of substituted biphenyl derivatives with low picomolar activities. SAR and pharmacokinetic characterization of this series are presented.

Animals↗
PubMed2001

Removal of ECG interference from the EEG recordings in small animals using independent component analysis.

In experiments involving small animals, the electroencephalogram (EEG) recorded during severe injury and accompanying resuscitation exhibit the strong presence of electrocardiogram (ECG). For improved quantitative EEG (qEEG) analysis, it is therefore imperative to remove ECG interference from EEG. In this paper, we validate the use of independent component analysis (ICA) to effectively suppress the interference of ECG from EEG recordings during normal activity, asphyxia and recovery following asphyxia. Two channels of EEG from five rats were recorded continuously for 2 h. Simultaneous recording of one channel ECG was also made. Epochs of 4 s and 1 min were selected from baseline, asphyxia and recovery (every 10 min) and their independent components and power spectra were calculated. The improvement in normalized power spectrum of EEG obtained for all animals was 7.71+/-3.63 db at the 3rd minute of recovery and dropped to 1.15+/-0.60 db at 63rd minute. The application of ICA has been particularly useful when the power of EEG is low, such as that observed during early brain hypoxic-asphyxic injury. The method is also useful in situations where accurate indications of EEG signal power and frequency content are needed.

Algorithms↗
PubMed2001

Three membrane-proximal amino acids in the human parainfluenza type 2 (HPIV 2) F protein are critical for fusogenic activity.

In this study, we investigated the role of the membrane-proximal region of the human parainfluenza virus type 2 (HPIV2) F protein by mutational analysis, including deletion, insertion, and substitution. Deletion or replacement of the entire 12 amino acid region (aa 474-485) of the HPIV2 F protein completely abolished its fusion activity when coexpressed with the HPIV2 HN protein. Deletion of groups of four of aa 478-485, single alanine, or other amino acid substitutions among aa 478-485 had minimal or limited effects on HPIV2 F/HN-induced cell fusion. However, a significant reduction in, or complete inhibition of, fusion activity was observed when aa 474-477 were deleted, or the N475, F476, or F477 residues were singly substituted with alanine. In addition, insertions of four amino acids at this region or deletion of eight or more amino acids significantly reduced F protein fusion activity. The oligomerization patterns and levels of cell surface expression of the mutant F proteins were compared to those of the wild-type HPIV2 F protein. The mutant HPIV2 F proteins defective in fusion were also found to be unable to initiate hemifusion, indicating that there is a specific requirement for three specific amino acids as well as the spacing in this region for initiating lipid mixing.

Amino Acids↗
PubMed2001

Numerical simulations of angiogenesis in the cornea.

Angiogenesis plays important roles in many physiologic and pathologic processes in the body. To understand mechanisms of angiogenesis, we developed a mathematical model for quantitative analysis of various biological events involved in angiogenesis. Our model was focused on two-dimensional angiogenesis in the cornea. The model considered diffusion of angiogenic factors, uptake of these factors by endothelial cells, and randomness in the rate of sprout formation and the direction of sprout growth. Our simulation results indicated that redistribution and uptake of angiogenic factors during angiogenesis had significant effects on the structure of vascular networks. A decrease in the uptake rate resulted in increases in vessel density, self-loop formation, and front migration speed of vascular networks. The randomness in the direction of sprout formation determined the curvature of vessels, whereas the probability of sprout formation from a vessel segment had a significant effect on the total number of vessels in vascular networks. The vascular networks generated in numerical simulations were similar to those observed experimentally. The mathematical model developed in this study can be used to evaluate effects of individual factors on angiogenesis, understand mechanisms of interactions among different factors during angiogenesis, and generate experimentally testable hypotheses.

Animals↗
PubMed2001

Dosimetric validation for multileaf collimator-based intensity-modulated radiotherapy: a review.

The creation of intricate dose distributions produced by intensity-modulated radiotherapy (IMRT) depends on complex planning systems and specialized mechanical devices. The many possible sources of inaccuracy and the complexity of the dose maps themselves require that a substantial effort be made to ensure that calculated and delivered dose distributions agree. This review provides an overview of the current status of the validation of dose predictions of IMRT planning systems by comparisons with measurements. Emphasis is placed on multileaf collimator- (MLC) based IMRT. Discrepancies between calculations and measurements may be due to any of 3 causes: errors and uncertainties in the dose calculation algorithm, in measurements, or in beam delivery by the accelerator/MLC combination. Some of the factors affecting dosimetry include: the technique employed for modulating the fluence, the dose calculation algorithm and other aspects of the planning system, mechanical limitations of the MLC hardware, dosimetric characteristics of the MLC, such as MLC leakage and rounded leaf ends, the choice of dosimeter, and the measurement geometry and technique. The advantages and drawbacks of various dosimeters including film, ion chambers, thermoluminescent dosimetry, and electronic portal imaging devices are discussed. The steps involved in validating dosimetrically a planning system are outlined, including the various fields that need to be measured, the phantoms that may be used, and measurement techniques. The achievable accuracy of dosimetry for IMRT is discussed.

Radiometry↗
PubMed2001

The use of echocardiographic colour kinetic wall motion to differentiate broad complex tachycardia.

Discrimination between supraventricular tachycardia (SVT) with aberrant conduction from ventricular tachycardia (VT) is vital for the safe and effective management of both conditions. Electrocardiographic algorithms for the differentiation of broad complex tachycardia are complex and difficult to implement in the acute setting, with misdiagnosis occurring in up to 40% of acute presentations. This case study shows the potential for echocardiographic colour kinesis (eck) to support electrocardiographic differentiation. A 74-year old man in sinus rhythm with left bundle branch block (lbbb), a history of myocardial infarction and recurrent sustained VT underwent eck analysis of wall motion propagation during a programmed electrical ventricular stimulation study. Sequential 40 ms time frames of echocardiographic colour coded endocardial wall motion velocity were recorded on video during both induced VT of lbbb configuration and near isochronic atrially paced tachycardia in lbbb. During VT there was initial eck propagation of ventricular septal wall motion from the apex to the atria secondary to electrical depolarisation. During atrially paced tachycardia initial eck motion developed in the interatrial septum and atrial wall followed by propagation in the ventricular endocardial septal wall motion from the atria toward the ventricular apex. This eck technique potentially could be used to support the electrocardiographic diagnosis of a broad complex tachycardia.

Aged↗
PubMed2001

Serum vitamin A concentrations and growth in children and adolescents in Gansu Province, China.

The association between serum vitamin A concentration and growth was assessed in a random sample of 650 children aged 0-14 years and 143 adolescents aged 15-19 years from the four prefectures of Jiayuguan, Linxia, Lanzhou and Tianshui in Gansu Province, China. Serum vitamin A concentrations were measured using a high performance liquid chromatograph. Height and weight were measured with standard methods. The results show that serum vitamin A concentration appeared to be the lowest in the age group 5-9 years which was only 0.28 mg/mL (95% confidence interval [CI]: 0.27-0.30) in males and 0.30 mg/mL (95% CI: 0.28-0.32) in females; and then it gradually increased with age. There was no statistically significant difference between males and females in any of the age groups. There were statistically significant correlations between vitamin A and weight (r = 0.37; P <0.001) and body mass index (r = 0.26; P < 0.001). This study suggests that serum vitamin A concentrations in children and adolescents may affect child growth. Concerted efforts to improve vitamin A status from a very early age become increasingly important if vitamin A has a genuine impact on child growth.

Adolescent↗
PubMed2001

A practical approach to inverse planning for high-precision dose escalated conformal prostate radiotherapy.

The problem of choosing the best gantry angles and beam weights for dose-escalated conformal prostate treatment planning is formulated using a mixed-integer linear programming approach, to account for tumour dose homogeneity and dose-volume constraints. The formulation allows the number of beams to be restricted and for some of the beams to be compulsory. The present planning algorithm interfaces with and utilizes the three-dimensional planning capabilities of a commercial treatment planning system. A case study is illustrated, which represents a particularly challenging planning problem due to a large planning target volume and an unusually small bladder. Treatment plans with different numbers of beams are generated to compare with each other and with the standard six-field plan. Significant improvement is shown in the reduction of hot regions within the femoral heads and rectal wall, while not unduly compromising homogeneity constraints for the tumour.

Humans↗
PubMed2001

Determinants of smoking and cessation during and after pregnancy.

Smoking during pregnancy is harmful to both the foetus and the woman herself. However, in spite of educational efforts, a substantial proportion of pregnant women continue to smoke and many women who do stop smoking during pregnancy resume smoking following childbirth. To foster successful maternal smoking cessation, public health professionals need to focus on the major determinants of smoking and cessation during and after pregnancy, and then to address these with their intervention efforts. It is important to review contemporary epidemiological evidence on this significant public health issue. We have identified nine cohort studies, published in international peer-reviewed journals, that have examined determinants of smoking and cessation in pregnant women. The results indicate that the determinants of pregnant smoking and cessation include maternal age, dose and duration of smoking, partner's smoking habit, socioeconomic status, level of education, age to start smoking, level of addiction, parity and passive smoking. However, many other psychosocial factors, which may affect smoking status among pregnant women, remain to be identified. Evidence reviewed here suggests that a more focused, integrated approach and a more comprehensive assessment of major determinants of smoking and cessation during pregnancy will be required as part of any future intervention effort.

Female↗
PubMed2001

Antioxidant properties of carvedilol and metoprolol in heart failure: a double-blind randomized controlled trial.

Animal and human studies have shown that carvedilol has significant antioxidant properties compared with other beta-blockers. The objective of this study was to determine if these antioxidant effects are detectable in patients with heart failure and to compare carvedilol with the selective beta-blocker metoprolol. Twenty-four patients with chronic heart failure were randomly assigned to receive either carvedilol or metoprolol in a double-blind control trial for 12 weeks in a University teaching hospital clinic. Blood pressure, heart rate, exercise tolerance, left ventricular ejection fraction, plasma total antioxidant status, erythrocyte superoxide dismutase, and glutathione peroxidase activities were determined at baseline and every 4 weeks up to 12 weeks. The results showed that erythrocyte superoxide dismutase and glutathione peroxidase were significantly reduced in carvedilol treated patients after 12 weeks of therapy, whereas metoprolol had no significant effect, although the clinical improvement over the short-term was similar with both drugs. Thus carvedilol, in addition to improving symptoms in heart failure, also possesses significant antioxidant properties. Whether this additional action influences long-term outcome is at present unknown.

Adrenergic beta-Antagonists↗
PubMed2001

Available space and extracellular transport of macromolecules: effects of pore size and connectedness.

Molecular exclusion in tumor tissues is one of the limiting factors for drug delivery to tumor cells. It can be quantified by the available volume fraction of solutes (K(AV)). We found in a previous study that K(AV) of dextran in tumor tissues decreased sharply when the molecular weight (MW) of dextran was increased from 40,000 to 70,000. Outside this range, K(AV) was less sensitive to the MW of dextran. To understand the mechanisms of the MW dependence of K(AV), we investigated K(AV) in tissue phantoms composed of tumor cells in 1% agarose gels, and performed numerical simulations of the available volume fraction in pore networks. We found that the MW dependence of K(AV) in tissue phantoms was similar to that in tumor tissues when the volume fraction of cells in the former was approximately 30%. Our numerical simulations revealed that the sharp decrease in K(AV) required two necessary conditions: (i) the existence of at least two populations of pores and (ii) the lack of connectedness of available pores in the interstitial space. Furthermore, results in this study suggest that it is important to consider not only the local structures of pores but also their connectedness in analyses of molecular transport in tissues.

Biological Transport, Active↗
PubMed2001

Acceleration of dose calculations for intensity-modulated radiotherapy.

The requirements and trade-offs between accuracy and speed for radiotherapy dose computations have been discussed for decades. Inverse planning used for intensity-modulated radiotherapy (IMRT) optimization imposes additional demands on dose calculation since it is an iterative process in which dose calculations might be repeated many (10's to 1000's) of times. This work discusses the accuracy and speed issues as related to IMRT dose calculations. A hybrid dose calculation method which accelerates the optimization process is proposed and applied in which a fast-pencil beam (PB) model is used for initial optimization iterations, followed by superposition/convolution (SC) calculations. Optimization dose results are compared for pure PB optimization, pure SC optimization, and PB optimization followed by SC optimization. Plans were evaluated in terms of isodose coverage, dose-volume histograms, and total dose calculation time for five head and neck cases with diverse locations, sizes, and shapes for tumors and critical structures. Patient plans were designed for nine equispaced beams. For one patient, an additional five-beam configuration was tested. We found that gross features of intensity distributions resulting from all schemes were similar, however there were differences in the fine detail. Differences were small between composite dose distributions optimized with PB and SC methods, yet differences in individual beam dose distributions were quite significant. When the SC method was used to compute dose following optimization with PB method, dose differences were reduced significantly both for composite plans and for individual beams. Substantial overall timesavings were observed, allowing IMRT dose planning to become a more interactive activity.

Algorithms↗