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C Lee

Publications and source records attributed to C Lee.

At least 73 records · Page 4Linked to original sources
PubMed2004

Genome-wide detection of alternative splicing in expressed sequences using partial order multiple sequence alignment graphs.

We present a method for high-throughput alternative splicing detection in expressed sequence data. This method effectively copes with many of the problems inherent in making inferences about splicing and alternative splicing on the basis of EST sequences, which in addition to being fragmentary and full of sequencing errors, may also be chimeric, misoriented, or contaminated with genomic sequence. Our method, which relies both on the Partial Order Alignment (POA) program for constructing multiple sequence alignments, and its Heaviest Bundling function for generating consensus sequences, accounts for the real complexity of expressed sequence data by building and analyzing a single multiple sequence alignment containing all of the expressed sequences in a particular cluster aligned to genomic sequence. We illustrate application of this method to human UniGene Cluster Hs.1162, which contains expressed sequences from the human HLA-DMB gene. We have used this method to generate databases, published elsewhere, of splices and alternative splicing relationships for the human, mouse and rat genomes. We present statistics from these calculations, as well as the CPU time for running our method on expressed sequence clusters of varying size, to verify that it truly scales to complete genomes.

Alternative Splicing↗
PubMed2004

Evaluation of intra- and inter-fraction motion in breast radiotherapy using electronic portal cine imaging.

Breast irradiation is one of the most challenging problems in radiotherapy due to the complex shape of the target volume, proximity of radiation sensitive normal structures and breathing motion. It was the aim of the present study to use electronic portal imaging (EPI) during treatment to determine intra- and inter-fraction motion in patients undergoing radiotherapy and to correlate the magnitude of motion with patient specific parameters. EPI cine images were acquired from the medial tangential fields of twenty radiotherapy patients on a minimum of 5 days each over the course of their treatment. The treatments were administered using 10 MV X-rays and dynamic wedges on a Varian Clinac 2100CD linear accelerator. Depending on the incident dose and the angle of the wedge, between 4 and 16 images could be acquired in one session using an EPI device based on liquid ionization chambers (Varian). The border between lung and chest-wall could be easily detected in all images and quantitative measurements were taken for the amount of lung in the field and the distance of the breast tissue from the field edges. Inter-fraction variability was found to be about twice as large as intra-fraction variability. The largest variability was detected in cranio/caudal direction (intra-fraction: 1.3 +/- 0.4 mm; inter-fraction: 2.6 +/- 1.3 mm) while the lung involvement varied by 1.1 +/- 0.2 mm and 1.8 +/- 0.6 mm intra- and inter-fraction, respectively. This indicates that the effect of breathing motion on the amount of radiated lung was not of major concern in the patients studied. Of other patient specific parameters such as body weight, breast separation, field size and location of the target, only increasing age was significantly correlated with larger inter-fraction motion. Acquisition of EPI cine loops proved to be a quick and easy technique to establish the amount of patient movement during breast radiotherapy. The relatively small variability found in the present pilot study justifies considerations for more conformal dose delivery.

Aged↗
PubMed2004

A risk reduction approach for schizophrenia: the Early Psychosis Intervention Programme.

Schizophrenia is a serious mental disorder with a profound impact on patients, their caregivers and society. Most patients who develop schizophrenia experience a prodromal phase where there is a change in premorbid functioning prior to the onset of frank psychotic symptoms. Once psychosis sets in, the subsequent course can be variable but schizophrenia tends to run a chronic course, resulting in considerable disabilities. The prognosis of schizophrenia could potentially be improved by reducing the duration of untreated psychosis (DUP). The Early Psychosis Intervention Programme (EPIP) in Singapore adopts a risk-reduction approach. It seeks to reduce the DUP through public education, networking with the primary healthcare providers (general practitioners, counsellors, traditional healers), and the screening of conscripts into the Singapore Armed Forces. Integral to this programme is a service for those in the prodromal phase of psychosis, that addresses the concerns of stigmatisation and pharmacotherapeutic interventions. Our tertiary prevention strategies aim to reduce mortality and morbidity, and to improve the quality of the lives of the individuals diagnosed with this disorder through a comprehensive and holistic management programme that comprises case-management, the judicious use of antipsychotics, and various psychosocial interventions. Since EPIP's initiation in April 2001, there has been a steady increase in the number of individuals screened and accepted into the programme. Our networking strategy is gaining momentum and there has been a significant increase in the number of primary healthcare providers whom we have trained to identify early signs of psychosis. However, there remain various challenges which we are yet to overcome.

Combined Modality Therapy↗
PubMed2003

Grammatical and resource components of sentence processing in Parkinson's disease: an fMRI study.

BACKGROUND: Sentence comprehension requires linguistic processing as well as cognitive resources such as working memory (WM) and information-processing speed (IPS). The authors hypothesize that sentence comprehension difficulty in patients with mild PD is due to degradation of the large-scale neural network that supports cognitive resources during sentence processing. OBJECTIVE: To understand the neural basis for sentence comprehension difficulty in PD. METHOD: Regional brain activity with blood oxygenation level-dependent fMRI was monitored while seven PD patients and nine healthy seniors answered a simple probe about written sentences that vary in their grammatical and cognitive resource properties. RESULTS: Healthy seniors recruited posterolateral temporal and ventral inferior frontal regions of the left hemisphere, brain regions associated with grammatical processing that were also activated by PD patients. Healthy seniors also recruited left dorsal inferior frontal, right posterolateral temporal, and striatal regions that are associated with cognitive resources during sentence processing. Direct contrasts showed that striatal, anteromedial prefrontal, and right temporal regions are recruited to a significantly lesser degree in PD, but these patients have increased activation of right inferior frontal and left posterolateral temporal-parietal areas during sentence comprehension. CONCLUSION: These findings associate impaired sentence comprehension in PD with interruption of a large-scale network important for cognitive resources during sentence processing. These results also imply compensatory up-regulation of cortical activity that allows patients with mild PD to maintain sentence comprehension accuracy.

Aged↗
PubMed2003

Measurement of strain-dependent toxicity in the indene bioconversion using multiparameter flow cytometry.

The bionconversion of indene to cis-(1S,2R)-indandiol, a potential key intermediate in the synthesis of Merck's HIV protease inhibitor, CRIXIVAN trade mark, can be achieved using Rhodococcus, Pseudomonas putida, and Escherichia coli strains. This study reports on the application of multiparameter flow cytometry for the measurement of cytoplasmic membrane integrity and membrane depolarization as indicators of toxic effects of the substrate, product, and by-products using each of these strains. Measurements of oxygen uptake rate (OUR) and optical density (OD) as indicators of metabolic activity and biomass growth, respectively, were also made. Measurements of the cytoplasmic membrane potential, cell viability, and respiratory activity provided a sensitive set of parameters to assess toxicity in the indene bioconversion and provided the basis for process improvements and strain selection. The toxic concentrations of the substrate, product, and by-products for each strain have been determined. The results show that it is possible to accumulate cis-(1S,2R)-indandiol and cis-1-amino-2-indanol up to 20 g/L without significant negative effects on cell physiology using any of the strains tested. The Gram-negative P. putida (421-5 and GM 730) and E. coli strains were more resistant to indene and the isolated chemicals of the biotransformation than the Gram-positive Rhodoccoccus I24 strain, possibly due to the presence of the outer membrane and efflux pump mechanisms. P. putida GM 730 and the E. coli TDO 123 strains responded similarly to toxic effects, and the E. coli TDO 123 strain was more resistant than the P. putida 421-5 strain. In addition to the recommendations for strain selection, the identified targets for bioprocess improvement include a combination of genetic as well as process engineering approaches.

Bioreactors↗
PubMed2003

Expression of angiogenic factors during distraction osteogenesis.

Distraction osteogenesis is a unique and effective way to treat limb length inequality resulting from congenital and posttraumatic skeletal defects. However, despite its widespread clinical use, the cellular and molecular mechanisms by which this surgical treatment promotes new bone formation are not well understood. Previous studies in distraction osteogenesis have noted increased blood flow and vessel formation within the zone of distraction. These observations suggest that distraction osteogenesis may be driven in part by an angiogenic process. Using immunohistological analysis, the expression of two different angiogenic factors (VEGF and bFGF) was shown to localize at the leading edge of the distraction gap, where nascent osteogenesis was occurring. These cells were spatially adjacent to new vessels that were identified by staining for factor VIII. Microarray analysis detected maximal mRNA expression for a wide variety of angiogenic factors including angiopoietin 1 and 2, both Tie receptors, VEGF-A and -D, VEGFR2, and neuropilin 1. Expression of these factors was found to be maximal during the phase of active distraction. Expression of mRNA for extracellular matrix proteins and BMPs was also maximal during this period. A comparison between the patterns of gene expression in fracture healing and distraction osteogenesis revealed similarities; however, the expression of a number of genes showed selective expression in these two types of bone healing. These data suggest that bone formation during distraction osteogenesis is accompanied by the robust induction of factors associated with angiogenesis and support further investigations to elucidate the mechanisms by which angiogenic events promote bone repair and regeneration.

Angiogenesis Inducing Agents↗
PubMed2003

Enhanced immunogenicity of human papillomavirus 16 L1 genetic vaccines fused to an ER-targeting secretory signal peptide and RANTES.

To increase the potency of human papillomavirus (HPV) DNA vaccines, we constructed a series of HPV16 L1 vaccines genetically fused with a secretion signal and/or immune cell-recruiting RANTES. The DNA vaccines encoding secretory HPV L1 were constructed by inserting HPV L1 gene into a vector with an ER-targeting secretory signal sequence. The expression plasmid encoding secretory HPV L1 (pER/L1) was fused with cDNA of RANTES, generating pER/L1/R. For comparison, HPV L1 genes were cloned into pVAX1 vector with no signal sequence (pL1), and further linked to the N-terminus (pL1/R) or C-terminus of RANTES (pR/L1). The secretion of L1 proteins was observed in the pER/L1, pER/L1/R, and pR/L1-transfected cells, except the pL1/R-transfected group. Cytoplasmic localization of L1 protein was observed in the cells transfected with pL1/R, but not with pER/L1/R at 48 h after transfection. In mice, RANTES-fused vaccines more effectively elicited the levels of HPV16 L1-specific IgG and IgG2a antibodies than pL1. Of RANTES-fused vaccines, pER/L1/R encoding the secreted fusion protein induced the highest humoral and CD8(+) T-cell-stimulating responses. These results suggest that the immunogenicity of HPV L1 DNA vaccines could be enhanced by genetic fusion to a chemokine and secretory signal peptide sequences.

Antibodies, Viral↗
PubMed2003

Social adjustment in three cultures: data from families affected by chronic blood disorders. A sibling study.

This study explores the rate of psychosocial dysfunction in affected and unaffected children from families with haemophilia or beta-thalassaemia, as part of a cross-sectional, multicentre study into the resilience of 115 families with blood disorders. Sociodemographic and developmental data were collected from the parents using a standardized and semi-structured interview format, and medical data were obtained from the clinician. The children's social functioning over the year prior to the assessment was assessed with The Social Adjustment Scale adapted for school-aged children. Children with beta-thalassaemia showed significantly higher rates of social dysfunction than their unaffected siblings or children with haemophilia and their siblings. Older children showed significantly higher social dysfunction at school. The high rate of social dysfunction in children with beta-thalassaemia compared with unaffected siblings is likely to have a basis in the negative experiences associated with their medical problems. In contrast, the therapeutic advances in haemophilia allows boys to lead an almost normal life. Overall, the rates of social dysfunction in families with both these disorders proved commoner than reported in population surveys, but with the unavailability of local population controls, caution needs to be exercised in the interpretation of this finding.

Adolescent↗
PubMed2003

The prevalence of lower urinary tract symptoms in men and women in four centres. The UrEpik study.

OBJECTIVE: To evaluate the epidemiology of lower urinary tract symptoms (LUTS) among men and women, as there are significant unanswered questions about the prevalence and impact of LUTS in different populations. SUBJECTS AND METHODS: A population-based, cross-sectional survey was completed in Boxmeer (the Netherlands), Auxerre (France), Birmingham (UK) and Seoul (Republic of Korea), using culturally and linguistically validated versions of the International Prostate Symptom Score (IPSS). The aim was to estimate the distribution of symptoms of LUTS in men and women. Stratified random samples of men aged 40-79 years in each community were collected. Postal questionnaires were used in Europe and direct interviews in Korea. RESULTS: In all, 4979 index men and 3790 women were recruited, with age-adjusted response rates among men of 72% in Boxmeer, 28% in Auxerre, 60% in Birmingham and 68% in Seoul. The percentages of men and women with an IPSS of 8-35, indicating moderate to severe symptoms, were, respectively, 20.7 and 18.0 (Boxmeer); 19.2 and 12.6 (Auxerre); 25.1 and 23.7 (Birmingham); 16.2 and 19.9 (Seoul). Among women the relationship between symptoms and age was not as strong as in men. The percentages of men and women with moderate to severe symptoms were by age group, respectively, 10.6, 15.5 (40-49); 19.0, 18.2 (50-59); 30.5, 23.8 (60-69); 40.4, 28.7 (70-79). Among those aged 40-49 the main differences between men and women were in the questions about frequency of urination during the day and holding back urine. Among the older groups men reported more symptoms on all questions apart from urination at night and difficulty in holding back urine, both of which were equally prevalent among men and women. CONCLUSIONS: The overall prevalence of LUTS was high and showed no marked cultural variation. Prevalence increased with age, with severe LUTS commoner in older men. Women reported similar levels of the symptoms traditionally associated with LUTS in men. In each age group there were no major cultural differences in the frequency of LUTS. There were differences with age between men and women; younger men had a lower prevalence of LUTS than younger women but older men a much higher prevalence than older women. These findings emphasize that the IPSS should be confined to within-patient comparisons and not used as a diagnostic tool. The IPSS performs very similarly regardless of gender.

Adult↗
PubMed2003

The relationship between lower urinary tract symptoms and health status: the UREPIK study.

OBJECTIVES: To assess the hypothesis that as lower urinary tract symptoms (LUTS) increase in severity, the impact as measured by the BPH impact index (BII) would also increase. SUBJECTS AND METHODS: The UREPIK survey collected information on this relationship from men and their partners in the Netherlands, Korea, France and the UK. Culturally and linguistically validated versions of three standard questionnaires, the SF-12, the BII and the International Prostate Symptom Score (IPSS) were used to assess the distribution of symptoms and the impact on health status. Stratified random samples of men aged 40-79 years in each community were recruited. Response rates were 72% in Boxmeer, 28% in Auxerre, 60% in Birmingham and 68% in Seoul. Regression analyses were undertaken on total SF-12, BII and IPSS. RESULTS: In all, 4800 index men and 3674 women responded; the BII increased with increasing IPSS. The correlation coefficients were; Boxmeer 0.69, Auxerre 0.56, Birmingham 0.60 and Seoul 0.68. For women, the correlations were slightly lower except in Birmingham, at 0.65 (Boxmeer), 0.44 (Auxerre), 0.71 (Birmingham), 0.57 (Korea). BII scores were higher in women than in men with the same level of IPSS. Adjusting for IPSS there was no association between age and BII. There was an association between IPSS quality-of-life (QoL) score and BII; for men the correlation was 0.62 and for women 0.60. Men and women with the same score on the IPSS QoL reported the same bother. Among those with an IPSS of 20-35 women expressed significantly more bother (P < 0.001). The SF-12 scores decreased as the IPSS and the BII increased in both men and women. Furthermore, the SF-12 mental score decreased with increasing symptoms in the partner. CONCLUSIONS: The relationship between the severity of LUTS and BII was similar in all centres. There is a clear association between the BII and the IPSS QoL question in men and women. The BII discriminates between people who are unhappy about their urinary condition compared with those who are pleased. Although designed for use in men with benign prostatic hyperplasia, the index also appears to be a useful among women. The severity of symptoms of LUTS has an adverse effect on the health status of the individual and his/her partner.

Adult↗
PubMed2003

The association between lower urinary tract symptoms and erectile dysfunction in four centres: the UrEpik study.

OBJECTIVE: To report a large-scale multinational investigation of lower urinary tract symptoms (LUTS) and sexual function, designed to investigate the independent association between them, as recent small-scale epidemiological studies suggest an association between benign prostatic hyperplasia and sexual dysfunction; both conditions are strongly associated with age and no study has been able to exclude age as a confounding factor in this relationship. SUBJECTS AND METHODS: Culturally and linguistically validated versions of standard questionnaires were used to estimate the prevalence of LUTS (using the International Prostate Symptom Score, IPSS) and erectile dysfunction (ED) score (using O'Leary's Sexual Function Inventory) in regions of the UK (Birmingham), the Netherlands (Boxmeer), France (Auxerre) and Korea (Seoul). In each centre, stratified random samples were selected from population registers to provide representative samples of the population of men aged 40-79 years (and their partners) in each community. Direct interviews were held in Seoul and postal questionnaires used in the three European centres. The samples were selected randomly, providing representative samples in each community. RESULTS: In all, 4800 men and 3674 women responded; the response rates among men were 77% in Boxmeer, 21% in Auxerre, 42% in Birmingham and 65% in Seoul. The overall prevalence of ED for men aged 40-79, estimated as an ED score of 0-4, was 21.1%. There was evidence of a linear increase with age (P < 0.001) and the pattern was very similar in the four centres. From the weighted logistic model, there was evidence of an association between sexual dysfunction, other self-reported diseases and lifestyle. From the ED score, after adjusting for age and country, men with diabetes were more likely to score of 0-4 (odds ratio 1.57, 95% confidence interval 1.09-2.25), as were those with high blood pressure (1.38, 1.09-1.75) and with an IPSS of 8-35 (1.39, 1.10-1.74). For lifestyle, smokers were more likely to score 0-4 (1.54, 1.23-1.92), while physical activity during leisure time was slightly associated with a reduction in the chance of scoring 0-4 (0.87, 0.77-0.99). The analysis gave the same results when repeated using self-reported ED instead of the dichotomised score. CONCLUSIONS: ED is clearly age-related and a problem for a large proportion of men in the community. It can have a profound impact on the quality of life of the man and on his partner. Were all men with this problem to seek medical help there would be a large burden on healthcare systems. There are cultural and age effects on the assessment of this problem.

Adult↗
PubMed2003

The prevalence of male urinary incontinence in four centres: the UREPIK study.

OBJECTIVES: To report the results of the prevalence and health status associated with male urinary incontinence (UI) in a population-based, multicentre study in four countries, and to assess the epidemiology of this condition. SUBJECTS AND METHODS: A standard questionnaire asking about frequency and amount of urine loss, use of pads and stress incontinence, was used to measure the prevalence of UI among men in four countries (Boxmeer, The Netherlands; Auxerre, France; Birmingham, UK; and Seoul, Korea). Self-reported urinary leakage was also recorded, with details of visits to the doctor for the symptoms. The samples were selected randomly from population registers of men aged 40-79 years, which provided representative samples in each community. RESULTS: In all, 4979 men responded; from incontinence symptom scores, 7.3% of men aged 40-79 years in Auxerre, 16.3% in Boxmeer, 14.4% in Birmingham and 4.3% in Seoul reported mild to severe UI. On a self-reported question, 14.8% and 14.5% of men in Birmingham and Boxmeer thought that they had urinary leakage, compared with 7.5% and 7.1% of men in Auxerre and Seoul, but typically the reported incontinence was leaking drops of urine a few times a week. Of men with urinary leakage in the three European centres, 25.9% visited the doctor with this problem, compared with only 9.0% of men in Seoul. Of men in the European centres, 5.9% used pads at least occasionally, compared with only 1.6% of men in Seoul. UI was age-related and the reporting of it varied among centres, with 14.4% of men in Birmingham and 12.7% of men in Boxmeer aged 40-49 years reporting mild to severe UI, compared with 5.2% in Auxerre and 1.9% in Seoul. Among men aged 60-69 years the corresponding percentages were 13.7% in Birmingham, 22.6% in Boxmeer, 9.2% in Auxerre and 8.0% in Seoul. CONCLUSIONS: UI is more common in older men and relatively uncommon among younger men. Some men reported no problems on the symptom questionnaire but replied positively to a direct question. Surprisingly many men wear protective pads at least occasionally as a result of their problem. UI appears to be a problem for men and which remains largely untreated; this may partly be a result of cultural differences.

Adult↗
PubMed2003

Comparison of myocardial infarction with sequential ligation of the left anterior descending artery and its diagonal branch in dogs and sheep.

We report a comparison of the effects of myocardial infarction in dogs and sheep using sequential ligation of the left anterior descending artery (LAD) and its diagonal branch (DA), with hemodynamic, ultrasonographic and pathological evaluations. Five animals were used in each group. After surgical preparation, the LAD was ligated at a point approximately 40% of the distance from the apex to the base of the heart, and after one hour, the DA was ligated at the same level. Hemodynamic and ultrasonographic measurements were performed preligation, 30 minutes after LAD ligation, and 1 hour after DA ligation. As a control, two animals in each group were used for the simultaneous ligation of the LAD and the DA. Two months after the coronary ligation, the animals were evaluated as previously, and killed for postmortem examination of their hearts. All seven animals in the dog group survived the experimental procedures, while in the sheep group only animals with sequential ligation of the LAD and DA survived. Statistically significant decreases in systemic arterial blood pressure and cardiac output, and an increase in the pulmonary artery capillary wedge pressure (PACWP) were observed one hour after sequential ligation of the LAD and its DA in the sheep, while only systemic arterial pressures decreased in the dog. Ultrasonographic analyses demonstrated variable degrees of anteroseptal dyskinesia and akinesia in all sheep, but in no dogs. Data two months after coronary artery ligation showed significant increases in central venous pressure, pulmonary artery pressure, and PACWP in the sheep, but not in the dog. Left ventricular end-diastolic dimension and left ventricular end-systolic dimension in ultrasonographic studies were also increased only in the sheep. Pathologically, the well-demarcated thin-walled transmural anteroseptal infarcts with chamber enlargement were clearly seen in all specimens of sheep, and only-mild-to-moderate chamber enlargements with endocardial fibrosis were observed in the dog hearts. In conclusion, this study confirms that the dog is not a suitable model for myocardial infarction with failure by coronary artery ligation despite negligent operative mortality, when compared directly with an ovine model.

Animals↗
PubMed2003

Undifferentiated sarcoma of the mitral valve with unique clinicopathologic presentation.

We report a case of undifferentiated sarcoma originating from the mitral valve in a 3-year-old boy who presented with embolic symptoms of the lower extremity. The tumor was demonstrated by echocardiography. The mass was removed under a mild hypothermic cardiopulmonary bypass with cold blood cardioplegia. Grossly, the mass was composed of multiple small nodules, and the histopathologic findings were compatible with an undifferentiated sarcoma. Postoperative chemotherapy was added. The patient remains without evidence of recurrence 18 months after surgery.

Cardiac Surgical Procedures↗
PubMed2002

Reversible sensorineural hearing loss.

We present an unusual case of temporary sensorineural hearing loss in a 6-year-old child due to carbon monoxide. This was shown on both the audiograms and confirmed with objective testing using otoacoustic emissions. Carbon monoxide poisoning is one of the few recognised causes of reversible sensorineural hearing loss, though it may also lead to a permanent deficit. This is discussed along with other potential causes of reversible sensorineural hearing loss.

Audiometry, Pure-Tone↗