Biomedical subjects

C E Tan

Publications and source records attributed to C E Tan.

At least 19 recordsLinked to original sources

PubMed2000

Making the diagnosis of biliary atresia using the triangular cord sign and gallbladder length.

BACKGROUND: To evaluate the accuracy and utility of the triangular cord sign and gallbladder length in diagnosing biliary atresia by sonography. MATERIALS AND METHODS: Sixty fasted infants with cholestatic jaundice aged 2-12 weeks were examined sonographically using a 5-10 MHz linear array transducer, focusing on the triangular cord sign (as described by Choi et al. [1]), the gallbladder, and ducts. The triangular cord is defined as a triangular or tubular echogenic density seen immediately cranial to the portal vein bifurcation; it represents the fibrotic remnant of the obliterated cord in biliary atresia. The findings were blinded to blood chemistry, (99 m)Tc-DISIDA hepatobiliary scintigraphy, and liver biopsy. Diagnosis of biliary atresia was confirmed at surgery and histology. Non-biliary atresia infants resolved medically. Comparative charges of the various investigations was made. RESULTS: ++ Twelve infants had biliary atresia, and ten demonstrated a definite triangular cord. The two false-negatives had small or nonvisualized gallbladders. No false-positives were recorded. Gallbladder length ranged from 0-1.45 cm with a mean of 0. 52 cm in biliary atresia compared to a mean of 2.39 cm in nonbiliary atresia infants. (99 m)Tc-DISIDA hepatobiliary scintigraphy showed no excretion (false-positive) in 23 % of nonbiliary atresia cases. Scintigraphy and liver biopsy charges were 2 and 6 times that of sonography, respectively. CONCLUSION: The triangular cord sign and gallbladder length together are noninvasive, inexpensive, and very useful markers for biliary atresia.

Bile Ducts, Extrahepatic↗

PubMed1999

A study in the relationships between leptin, insulin, and body fat in Asian subjects.

OBJECTIVE: To study the relationship of leptin concentrations with indices of obesity, fasting insulin, insulin resistance and lipid profiles (total cholesterol, low density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)- cholesterol and triglyceride) in an Asian cohort. DESIGN: Cross sectional study. SUBJECTS: A total of 133 healthy volunteers were enrolled (64 female: age: 25-61 y, body mass index (BMI): 18.7-45.1 kg/m2 and 69 male: age: 25-61 y, BMI: 19.3-35.0 kg/m2). MEASUREMENTS: Weight, height, waist and hip circumferences, blood pressure, lean body mass (by bioelectric impedence analysis (BIA)), plasma leptin and lipid profiles were taken after a 10 h fast. RESULTS: Percentage of body fat measured by bioelectric impedance was the strongest determinant of plasma leptin (r = 0.844, P < 0.0001). Females had higher leptin concentrations than males for the same fat mass. In a multiple linear regression model, body fat percentage, (percentage body fat* gender), hip circumference and fasting insulin were significant determinants of leptin concentration (r = 0.882, P < 0.0001). CONCLUSION: Leptin concentration correlated closely with percentage body fat in Asian subjects. Hip circumference as a corollary for peripheral obesity, was better associated with leptin than waist circumference or waist-to-hip ratio (WHR). Distribution of fat in females tended to be peripheral and may partly explain the gender difference. Fasting insulin level and central obesity were correlated with HDL-cholesterol, triglyceride and blood pressure, while fasting leptin had little correlation with these metabolic parameters. Therefore, insulin resistance was a better guide to cardiovascular risk assessment than plasma leptin.

Adipose Tissue↗

PubMed1999

Isolated low HDL cholesterol: an insulin-resistant state only in the presence of fasting hypertriglyceridemia.

Individuals with isolated low HDL cholesterol are at increased risk of coronary artery disease. It has been reported previously that this is an insulin-resistant state. We analyzed data from the 1992 Singapore National Health Survey with the objective of defining the clinical and metabolic parameters associated with isolated low HDL cholesterol. A total of 3,568 individuals were selected by stratified random sampling. Subjects with low HDL cholesterol (<0.9 mmol/l) and "ideal" total cholesterol (<5.2 mmol/l) were identified. Data on anthropometry, blood pressure (BP), insulin resistance, glucose tolerance, sex, smoking habit, and ethnic group were examined. We found that this group was heterogeneous. Those with fasting triglyceride (TG) >1.7 mmol/l (low HDL/high TG) displayed features of the insulin resistance syndrome characterized by obesity, higher diastolic BP, greater insulin resistance, and a greater tendency to have diabetes or impaired glucose tolerance (IGT). If fasting TG was <1.7 mmol/l (isolated low HDL cholesterol), individuals were similar to the general population in terms of insulin resistance and obesity. Both groups were more commonly men and Asian Indian. The ethnic difference in prevalence could not be explained by differences in diet, exercise, alcohol ingestion, or smoking. Our data support the view that Asian Indians are genetically predisposed to isolated low HDL cholesterol as well as the insulin resistance syndrome. The higher prevalence of isolated low HDL cholesterol, the young age at which individuals exhibit this phenotype (mean age 32.5 years), along with the greater propensity for Asian Indians to develop insulin resistance and IGT contribute to the threefold increased incidence of myocardial infarction in those <65 years of age in this ethnic group.

Adolescent↗

PubMed1999

Prevalence of diabetes and ethnic differences in cardiovascular risk factors. The 1992 Singapore National Health Survey.

OBJECTIVE: The purpose of the 1992 Singapore National Health Survey was to determine the current distribution of major noncommunicable diseases and their risk factors, including the prevalence of diabetes and dyslipidemia, in Singapore. RESEARCH DESIGN AND METHODS: A combination of disproportionate stratified sampling and systematic sampling were used to select the sample for the survey. The final number of respondents was 3,568, giving a response rate of 72.6%. All subjects fasted for 10 h and were given a 75-g glucose load, except those known to have diabetes. Blood was taken before and 2 h after the glucose load. Diagnosis of diabetes was based on 2-h glucose alone. RESULTS: The age-standardized prevalence of diabetes in Singapore residents aged 18-69 years was 8.4%, with more than half (58.5%) previously undiagnosed. Prevalence of diabetes was high across all three ethnic groups. The prevalence of impaired glucose tolerance was 16.1%, that of hypertension was 6.5%, and 19.0% were regular smokers. The total cholesterol (mean +/- SD) of nondiabetic Singaporeans was 5.18 +/- 1.02 mmol/l; 47.9% had cholesterol > 5.2 mmol/l, while 15.4% had levels > 6.3 mmol/l. Mean LDL cholesterol was 3.31 +/- 0.89 mmol/l; HDL cholesterol was 1.30 +/- 0.32 mmol/l, and triglyceride was 1.23 +/- 0.82 mmol/l. CONCLUSIONS: Prevalence of diabetes was high across all three ethnic groups. Ethnic differences in prevalence of diabetes, insulin resistance, central obesity, hypertension, smoking, and lipid profile could explain the differential coronary heart disease rates in the three major ethnic groups in Singapore.

Adolescent↗

PubMed1999

Development of the human intrahepatic biliary system.

In the development of the human biliary system, the extrahepatic bile ducts (EHBD) develop from the embryonic hepatic diverticulum, while the intrahepatic bile ducts (IHBD) originate within the liver from the ductal plate. The ductal plate is a flat muralium of primitive biliary epithelium that develops in the mesenchyme along the branches of the portal vein, by a process which requires a delicate balance between cell proliferation and death. The ductal plate is thus remodelled into the adult system of tubular anastomosing bile ducts and this process is called ductal plate remodelling. Computerised three-dimensional reconstruction of the developing ductal plate has shown that the ductal plate remodelling process starts at the porta hepatis around 11 weeks of gestation and progresses towards the periphery of the liver. The extrahepatic biliary system is in direct luminal continuity with the developing intrahepatic biliary system throughout gestation and does not have a "solid stage" as suggested previously. The ductal plate remodelling is controlled by many biochemical and molecular factors, some of which have been identified and studied. It has been suggested that abnormalities in the development of the IHBD could lead to a spectrum of diseases called ductal plate malformation. Biliary atresia is one of the conditions in this spectrum. Currently, we are studying the IHBD in biliary atresia in comparison to the normal developing IHBD, the results of which are presented in this review. Both morphologically and biochemically the IHBD in biliary atresia resembles the primitive foetal ductal plate suggesting a disruption in ductal plate remodelling.

Bile Ducts↗

PubMed1999

Experimental models of hepatic fibrosis in the rat.

The rat is a frequently used experimental model in studies involving human disease. We review several methods of inducing hepatic fibrosis and cirrhosis in rats. These include induction by hepatotoxins and hepatocarcinogens such as carbon tetrachloride, dimethylnitrosamine, thioacetamide and furan; the hepatoxin-cum-nutrient, alcohol; a high fat-low choline-low protein diet; immunologic agents such as heterologous serum or bacterial cell wall products; and obstructive jaundice and biliary cirrhosis by common bile duct ligation.

Animals↗

PubMed1999

A study to assess the effect of dietary supplementation with soluble fibre (Minolest) on lipid levels in normal subjects with hypercholesterolaemia.

Hypercholesterolaemia is one of the major risk factors in the development of coronary artery disease. In recent years, many nonprescription treatments have become available for cholesterol lowering. Minolest is a product that contains guar gum and psyllium as the principal active ingredients. We conducted a randomised, placebo-controlled, double-blind, parallel-group study to assess the efficacy of Minolest as a lipid-lowering agent. Secondary aims included assessment of the effect on blood pressure and obesity. We also looked at the acceptability of the product and side effects associated with its ingestion. After a 4-week run-in period, 83 subjects were randomised to receive placebo or Minolest (16.5 g/day) for 3 months. Seven subjects defaulted follow up, 5 in the placebo group and 2 in the active treatment group. In addition, 9 subjects (5 on active treatment and 4 on placebo) had total cholesterol fall into the optimal range (< 5.2 mmol/l) during the run-in phase and were removed from the study. At baseline in the active treatment group, total cholesterol was 6.1 (5.43 to 8.06) mmol/l, triglyceride 1.54 (0.56 to 4.19) mmol/l, HDL cholesterol 1.32 +/- 0.43 mmol/l and LDL cholesterol 4.1 (3.10 to 6.27) mmol/l. In the placebo group, total cholesterol was 5.84 (5.32 to 8.38) mmol/l, triglyceride 1.47 (0.69 to 11.0) mmol/l, HDL cholesterol 1.15 +/- 0.33 mmol/l and LDL cholesterol 3.87 (2.46 to 5.14) mmol/l. The differences in the baseline characteristics were not statistically significant except the LDL-cholesterol. Minolest produced a 3.24% (SD = 7.85%, P = 0.020) decrease in total cholesterol and 5.45% decrease in LDL cholesterol (SD = 10.25%, P = 0.0034) but no significant difference in serum triglyceride, weight, body mass index or blood pressure. This was not seen in the placebo group. The percentage fall in LDL cholesterol increased to 7.16% and 7.37% in subjects who consumed at least 50% and 70% of the treatment respectively. There were few side effects. The authors conclude that this product has a small impact on the lipid profile and may be useful only in subjects with mild hypercholesterolaemia and a low risk of coronary artery disease.

Adult↗

PubMed1999

Measurement of obesity by anthropometry and bioelectric impedance analysis: correlation with fasting lipids and insulin resistance in an Asian population.

Obesity is associated with increased coronary artery disease risk. This is at least partially mediated by increased prevalence of other risk factors such as dyslipidaemia and insulin resistance. Various anthropometric indices have been used to quantify generalised and central obesity. Correlations between these measurements and risk factors are specific to the population and findings cannot be extrapolated to other ethnic groups. Bioelectric impedance analysis (BIA) is a simple means of estimating percentage body fat. We compared body mass index (BMI), waist circumference, waist-hip ratio (WHR) and percentage body fat measure by BIA as predictors of fasting lipid profiles and insulin resistance in 109 Singaporean Chinese. BMI was significantly correlated with insulin resistance and there appeared to be a threshold at 26 kg/m2 above which the regression line became more steep. WHR best predicted fasting triglyceride in both men and women. In women, it was inversely correlated with high density lipoprotein cholesterol. A similar association was seen in men but this did not reach statistical significance. We conclude that measurement of BMI and WHR should be part of the assessment of cardiovascular risk in our population as they connote different aspects of risk. BIA was not found to be a useful tool for the prediction of coronary artery disease risk factors in our population.

Adult↗

PubMed1998

Salvia miltiorrhiza reduces experimentally-induced hepatic fibrosis in rats.

BACKGROUND/AIMS: Hepatic fibrosis occurs as a result of injury to the liver parenchyma and biliary system. We have studied the effect of the traditional Chinese medicinal herb, Salvia miltiorrhiza, in an experimental model of hepatic fibrosis and evaluated its effect on various paradigms involved in hepatic fibrosis. METHODS: Liver fibrosis was induced in male Wistar rats by chronic administration of carbon tetrachloride for 10 weeks. The carbon tetrachloride-treated rats were randomly assigned to three groups: no treatment, Salvia for 12 weeks from the onset of carbon tetrachloride treatment, and Salvia for 2 weeks after the completion of the 10-week course. The normal control groups in the study were: neither carbon tetrachloride nor Salvia, and Salvia only for 12 weeks. The livers were graded histologically and analyzed by reverse transcription-polymerase chain reaction for the transcription of genes involved in liver fibrosis, namely, transforming growth factor-beta1 and the extracellular matrix components procollagens I and III, tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-13. The transcripts were normalized against that of glyceraldehyde-3-phosphate dehydrogenase and analyzed statistically. RESULTS: The histological evaluation showed that Salvia could reverse the fibrosis caused by carbon tetrachloride treatment. Rats treated with the herb had reduced levels of transforming growth factor-beta1, procollagens I and III and tissue inhibitor of metalloproteinase-1 transcripts and an increased level of matrix metalloproteinase-13 transcript, when compared to the disease control. CONCLUSION: Salvia miltiorrhiza, a cheap and widely available herb, significantly reduces carbon tetrachloride-induced hepatic fibrosis in rats.

Animals↗

PubMed1998

Associations of indices of adiposity with atherogenic lipoprotein subfractions.

OBJECTIVE: To investigate the associations of indices of adiposity with cardiovascular risk factors. SUBJECTS: 93 men and 98 women aged 18-69 y. OUTCOME MEASURES: Body mass index (BMI), waist to hip ratio (WHR), waist circumference, waist to height ratio, blood pressure, fasting concentrations of blood glucose, insulin, plasma lipids and lipoprotein subfractions, apoproteins, lipoprotein(a) and post-heparin lipases. RESULTS: BMI and waist showed similar associations (P < 0.01) with a cluster of major cardiovascular risk factors including total cholesterol, low density lipoprotein-cholesterol and very low density lipoprotein-cholesterol in men, and ratio of low density lipoprotein-/high density lipoprotein-cholesterol for both genders. Large waist circumference was significantly (P < 0.01) associated (controlled for age and smoking) with features of the metabolic syndrome, including raised insulin concentration (men: r=0.37, women: r=0.49), reduced high density lipoprotein2 (men: r=-0.30, women: r=-0.34), increased very low density lipoprotein1 mass (men: r=0.31, women: r=0.42), raised small, dense low density lipoprotein (men: r=0.30, women: r=0.31), elevated blood pressure (men: r=0.27, women: r=0.28), increased triglyceride (men: r=0.43, women: r=0.48) and apolipoprotein-B (men: r=0.32, women: r=0.35). Waist circumference also correlated with hepatic lipase/lipoprotein lipase ratio in women (r=0.52). Height adjustment did not substantially change relationships between waist circumference and risk factors. WHR correlated with fewer risk factors. CONCLUSION: For the purpose of health promotion to prevent cardiovascular disease associated with overweight and intra-abdominal fat accumulation, the general public should be advised to be aware of the risk associated with large waist circumference.

Adipose Tissue↗

PubMed1998

The effect of smoking on post-heparin lipoprotein and hepatic lipase, cholesteryl ester transfer protein and lecithin:cholesterol acyl transferase activities in human plasma.

INTRODUCTION: Smoking is associated with dyslipidaemia, particularly raised plasma triglycerides and reduced high-density lipoprotein (HDL)-cholesterol and a delayed clearance of triglyceride in fat tolerance tests. The aim of this study was to investigate whether these phenomena could be explained by a reduced lipoprotein lipase activity in smokers. METHODS: A group of 40 healthy individuals [plasma cholesterol 5.07 (SD 0.90) mmol L-1, plasma triglyceride 1.02 (SD 0.39) mmol L-1)] was studied to examine the effects of smoking on plasma enzyme activities, particularly post-heparin lipase activities. The group comprised 20 smokers and 20 non-smokers, who were matched for age, gender and body mass index (BMI). RESULTS: Post-heparin lipoprotein lipase (LPL) activity [3.89 (SD 1.58) vs. 5.85 (SD 2.30) mumol free fatty acids (FFA) mL-1 h-1, P < 0.005], but not post-heparin hepatic lipase (HL) activity, was reduced in smokers. Plasma cholesteryl ester transfer protein (CETP) activity and lecithin: cholesterol acyl transferase (LCAT) activity were measured in a subgroup of 18 individuals, comprising nine smokers with nine matched non-smokers. There was no difference in CETP activities between two groups, but smokers had a significantly reduced plasma LCAT activity [112 (SD 23) vs. 152 (SD 24) nmol cholesterol mL-1 h-1, P < 0.005]. In both smokers (r=-0.53, P < 0.05) and non-smokers (r=-0.54, P < 0.05), HDL2 concentration was negatively associated with HL activity. In non-smokers, HDL3 concentration was negatively associated with CETP activity (r= -0.77, P < 0.05), whereas in smokers HDL3 concentration was negatively associated with LCAT activity (r= -0.78, P < 0.050). CONCLUSION: It was shown by direct measurement that the activity of plasma post-heparin LPL is reduced in smokers, independently of age, gender and BMI. It is concluded that this enzyme perturbation associated with smoking may contribute to the development of the atherogenic lipoprotein phenotype seen in smokers.

Adult↗

PubMed1998

Survey of aerobic bacterial infections in paediatric surgical intensive care unit patients.

Infections cause a significant amount of morbidity and mortality in paediatric surgical patients requiring intensive care. The study aims to describe the epidemiology of infection among these patients, to correlate the source of infection with the underlying medical condition, and to determine the antibiotic sensitivity pattern of the organisms. Through a retrospective review over a period of one year, 133 cases were analysed. The overall incidence of infection was 35%. Those who had emergency surgery had the highest infection rate (47%). Respiratory tract infections were the commonest source of infection, and were associated with ventilator therapy rather than the underlying medical condition. The Enterobacteriaceae were the most common isolates seen. From antibiotic sensitivity tests, the empirical antibiotics of choice are gentamicin for suspected gram-negative infection and vancomycin for severe infections where methicillin-resistant Staphylococcus aureus is a likely cause. A high rate of resistance to ampicillin was seen and its use as a first-line monotherapy drug should be discontinued in our patient population.

Ampicillin Resistance↗

PubMed1998

A case report of a patient with bronchial carcinoid tumour and late presentation of Cushing's syndrome.

Bronchial carcinoid tumour with ectopic adrenocorticotrophin (ACTH) production is an uncommon cause of Cushing's syndrome. In most instances, the patient presents with clinical hyperglucocorticolism and a search for its underlying pathology leads to the discovery of an inconspicuous bronchial carcinoid tumour, if at all. Often the tumour is not immediately detectable. We report a patient who presented in the reverse order--she initially had a large asymptomatic bronchial carcinoid tumour that subsequently manifested as clinical Cushing's syndrome after remaining quiescent for four years.

Adrenocorticotropic Hormone↗

PubMed1997

Developing human biliary system in three dimensions.

BACKGROUND: In the development of the human biliary system, although the extrahepatic bile ducts develop from the embryonic hepatic diverticulum, there is increasing evidence to suggest that the intrahepatic bile ducts originate within the liver from the ductal plate. The ductal plate develops as a sheath of primitive biliary epithelium in the mesenchyme along the portal vein branches. Through an orderly process of selection and deletion, the ductal plate is remodelled into the adult system of anastomosing tubular bile ducts. The ductal plate remodelling process occurs at the porta hepatis between 11 and 13 weeks of gestation and progresses towards the periphery of the liver. METHODS: In this project, for the first time, we have used computerised three-dimensional reconstruction techniques to visualise the developing human biliary system. Paraffin-embedded tissue from eight human embryos or fetuses between 5.5 and 16 weeks of gestation were serially sectioned, and their images were aligned, digitised, and used for three-dimensional reconstruction. RESULTS AND CONCLUSIONS: Three-dimensional images of the extrahepatic and the intrahepatic biliary systems were obtained, and the following conclusions were drawn. (1) The intrahepatic biliary system, both at the porta hepatis and within the liver, developed from the ductal plate through a consistent pattern of remodelling. (2) Prior to the remodelling process, the ductal plate was of similar morphology irrespective of site and gestation. (3) The extrahepatic biliary system was in direct luminal continuity with the developing intrahepatic biliary system throughout gestation and did not show the presence of a "solid stage" in any of the embryos or fetuses studied.

Bile Ducts, Extrahepatic↗

PubMed1997

Thyroid stimulating hormone receptor antibody levels in Singaporean patients with autoimmune thyroid disease.

Stimulating thyrotrophin receptor antibodies (TRAbs) have been identified as the antibodies responsible for the pathogenesis of Graves' disease (GD) while blocking TRAbs have been implicated as the cause of hypothyroidism in some patients with chronic lymphocytic thyroiditis (CLT). TRAb positivity in patients with other thyroid disorders such as silent thyroiditis, toxic multinodular goitre and subacute thyroiditis has been reported but the role of TRAb in these disorders is unclear. A study was carried out to determine the prevalence of TRAb positivity in Singaporean patients with a spectrum of thyroid diseases. TRAb levels were measured in 181 patients with GD, 54 patients with CLT (37 goitrous and 17 agoitrous), 16 patients with thyroid nodules, 11 patients with subacute thyroiditis, 1 patient with hyperthyroidism due to a human chorionic gonadotrophin (HCG)-secreting tumour, 2 patients with thyroid stimulating hormone-secreting tumours and 2 patients with amiodarone-induced dysthyroidism. Using a cut-off of 10.0 U/L, TRAb levels were found to be positive in 79.0% of GD patients, 9.2% of CLT patients (euthyroid and hypothyroid) and no patients with other thyroid disorders. TRAb was a more sensitive marker of GD than anti-thyroglobulin antibodies (53.2%) but not anti-microsomal (78.3%) antibodies. TRAb levels > 10.0 U/L appear to be highly specific for autoimmune thyroid disease.

Biomarkers↗

PubMed1997

Aldosterone to renin ratios in the evaluation of primary aldosteronism.

Primary aldosteronism, though an uncommon cause of hypertension, causes significant morbidity, making it important to diagnose and treat this condition. Its evaluation requires complex and time consuming investigative procedures in order to confirm the diagnosis and to differentiate between the subtypes of aldosterone producing adenoma and idiopathic hyperaldosteronism. Often, the values of renin and aldosterone are equivocal, and the diagnosis of primary aldosteronism is in doubt. In this study, we examine the use of aldosterone to renin ratios in confirming the diagnosis of primary aldosteronism when the usual criteria of suppressed renin and elevated aldosterone are not met. We have found that an aldosterone to renin ratio of 50 has a 100% specificity and 92% sensitivity for detecting primary aldosteronism. Also, an aldosterone to renin ratio of > 2000 is suggestive of an aldosterone producing adenoma.

Adrenocortical Adenoma↗

PubMed1996

Abnormal thyroid and adrenocortical function test results in intensive care patients.

A prospective, cohort study of 75 consecutive patients requiring management in the medical intensive care unit (MICU) of the Singapore General Hospital was carried out over a five-month period to determine thyroid and adrenocortical profiles and evaluate their use in predicting patient outcome. Up to 88% of patients had at least one abnormal thyroid function and 77% had abnormal adrenocortical function test results. There were significantly lower triiodothyronine, thyroxine and free thyroxine, but not thyrotropin levels, and higher cortisol levels in non-survivors compared to survivors (all P < 0.01). Of the endocrine parameters, triiodothyronine and cortisol concentrations were independent predictors of outcome. The overall predictive accuracy of combining these two variables on admission into the MICU was 74%. The APACHE II (acute physiology and chronic health evaluation II) score alone predicted outcome with 71% accuracy, and in combination with triiodothyronine and cortisol levels improved accuracy to 84%. The use of dopamine alone predicted outcome with 74% accuracy, and in combination with triiodothyronine and cortisol levels, improved accuracy to 84%. Measurements of total triiodothyronine and cortisol concentrations on admission to the MICU, and consideration of the use of dopamine improve on the APACHE II score in outcome prediction.

APACHE↗

PubMed1995

Distortion in TGF beta 1 peptide immunolocalization in biliary atresia: comparison with the normal pattern in the developing human intrahepatic bile duct system.

Biliary atresia is an important cause of neonatal obstructive jaundice in which there is inflammation, sclerosis and eventual obliteration of the bile duct system. Its onset may be antenatal, affecting the normal development of the biliary system. The intrahepatic biliary system is derived from the ductal plate, a sheath of cuboidal epithelium that appears at the hepatocyte-mesenchymal junction around the portal vein branches at 6 weeks gestation. This epithelial structure is moulded into a network of tubular bile ducts by the proliferating mesenchyme. Certain portions of the ductal plate are selected to become definitive bile ducts, while redundant biliary epithelium is deleted. The molecular dynamics controlling the intra-uterine development of the biliary system in humans are not yet clearly understood. Transforming growth factor-beta 1 is a cytokine that stimulates mesenchymal proliferation and inhibits epithelial growth, and has been shown to be important in organogenesis. In the present study, the pattern of TGF beta 1 peptide immunolocalization was investigated with the aid of computerized image analysis, in normal human bile duct development and in biliary atresia. TGF beta 1 peptide was detected within hepatocytes and ductal plate epithelium from 7 weeks gestation; increased TGF beta 1 immunoreactivity was present within the epithelium of developing bile ducts at 13 weeks gestation, and apical polarization of the cytokine was observed from 16 weeks gestation. In biliary atresia, the TGF beta 1 immunoreactivity pattern within the bile duct structures at the porta hepatis and within intrahepatic portal tracts resembled that of the primitive ductal plate, and there was no significant apical polarization. This may indicate a developmental arrest in the normal ductal plate remodelling process in biliary atresia, and suggests an underlying epithelial-mesenchymal interactive disorder.

Adolescent↗