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Biomedical subjects

E Lau

Publications and source records attributed to E Lau.

At least 37 records · Page 2Linked to original sources
PubMed2000

Isolation and sequencing of cDNAs for the XL-I and XL-III forms of bovine liver xenobiotic-metabolizing medium-chain fatty acid:CoA ligase.

The XL-I form of xenobiotic-metabolizing medium-chain fatty acid:CoA ligase was previously purified to apparent homogeneity from bovine liver mitochondria, and the amino acid sequence of a short segment of the enzyme was determined. This sequence was used to develop a probe for screening a bovine cDNA library from which a 1.6 kb cDNA was isolated. This cDNA was sequenced and found to contain the code for the known amino acid sequence. The complete open reading frame was not present in this cDNA, but it was estimated to code for approximately 75% of the XL-I sequence. The XL-III ligase was purified to apparent homogeneity from bovine liver mitochondria. The enzyme eluted from a gel filtration column as a single peak with an apparent molecular weight of ca. 55,000. It ran as a single band on SDS-polyacrylamide gel electrophoresis (SDS-PAGE) with an apparent molecular weight of 62 kDa. N-Terminal sequence analysis of the enzyme gave no sequence, which indicates a blocked N-terminus. The enzyme was chemically cleaved using CNBr. The resulting peptides were separated by SDS-PAGE. The cleavage pattern revealed two large peptides of ca. 21 and 25 kDa, plus several smaller peptides including a prominent 6 kDa peptide. The N-terminus of the 6, 21, and 25 kDa peptides was sequenced and the 21 and 25 kDa sequences were identical indicating incomplete cleavage. The sequences were used to design probes for screening a bovine liver cDNA library. This resulted in the isolation of a 2,065 bp cDNA. This cDNA was sequenced and found to contain the initiation and termination codons, as well as the requisite amino acid sequences. The open reading frame coded for a 64,922 Da protein. The sequence of XL-III cDNA was markedly different from that of XL-I, indicating the genetic uniqueness of the two ligases. They are, however, 64% homologous, which suggests a common evolutionary origin.

Amino Acid Sequence↗
PubMed2000

Monovalent cation effects on the activity of the xenobiotic/medium-chain fatty acid:CoA ligases are substrate specific.

The effect of monovalent cation on the activity of the XL-I and XL-III forms of xenobiotic/medium-chain fatty acid:CoA ligase (XM-ligase) was investigated using a variety of different carboxylic acid substrates. With benzoate or p-hydroxybenzoate as substrate, the XL-I ligase was essentially inactive in the absence of monovalent cation. However, with phenylacetic acid and medium-chain fatty acids as substrate, the enzyme retained 3 to 10% activity upon removal of monovalent cation. Further, while Na+ was ineffective with benzoate and p-hydroxybenzoate as substrates, it was effective with other substrates, although still less effective than K+. For XL-III, activity toward benzoate, hydroxybenzoate, and salicylate was insignificant in the absence of monovalent cation, but this rate was 10% of the K(+)-supported rate for hexanoate and 20% for decanoate. Also, with decanoate as substrate, XL-III was activated more by Na+ than by K+. Thus, the nature of the dependence on monovalent cation for activity is substrate-selective. Kinetic analysis of the effect of K+ on the activity of XL-I and XL-III revealed that activation by K+ was not the result of alteration of the affinity of the enzymes for either ATP or the carboxylic acid. For both forms of XM-ligase, K+ was found to enhance the affinity of the enzyme for CoA, regardless of the substrate, although the extent of the enhancement was substrate-specific. In almost all cases there was further activation, even at saturating concentrations of CoA, which indicates an additional effect of monovalent cation on the catalytic rate constant for the reaction. The exception was activation of XL-III activity toward decanoate, which was solely the result of enhanced binding affinity for CoA.

Animals↗
PubMed2000

A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia-a preliminary report.

We initially observed a phenomenon of reduced in vitro binding of exogenous cobalt [Co(II)] to the N-terminus of human serum albumin (HSA) in emergency chest pain patients with early onset unstable angina and myocardial infarction. We then developed a colorimetric assay to measure cobalt-HSA binding and record the results in absorbance units (ABSU). In a preliminary clinical study of 139 emergency patients with acute chest pain, 99 patients with evidence of myocardial ischemia (Group 1) had elevated assay levels (mean ABSU +/- SD; 0.519 +/- 0.086) compared to 40 patients (Group 2) with no evidence of ischemia (0.316 +/- 0.092) (p < 0.00001). In Group 1, 95 of 99 (96.0%) patients had levels higher than a decision threshold of 0.400 ABSU and in Group 2, 37 of 40 (92.5%) samples had higher cobalt binding capacity (ABSU </= 0.400). Further studies are warranted to determine if an assay measuring altered cobalt-HSA binding is a clinically useful diagnostic test to rule out myocardial ischemia.

Aged↗
PubMed2000

Thermocoagulation for selective reduction of conjoined twins at 12 weeks of gestation.

Conjoined twins occur rarely. Most of the prenatally diagnosed cases are terminated either because of extensive organ sharing or because of the presence of major structural abnormalities. We present a case of omphalopagus conjoined twins diagnosed at 10 weeks of gestation with selective reduction performed at 12 weeks. The twins were conjoined at the umbilicus with vascular communication demonstrated at the conjunction. Twin A was normal but twin B was growth restricted and hydropic. Thermocoagulation of twin B was performed at 12 weeks by passing an insulated electric wire through a 18-gauge needle placed close to the fetal heart. Reassessment at 15 weeks showed that twin A was growing normally with a small dead twin B attached at its umbilicus. Twin B was subsequently sloughed off from this attachment and could be seen lying free in the amniotic cavity at 17 weeks. Twin A was delivered at term and was healthy. A small scar could be seen just above the umbilical cord insertion. This case represents the first antenatal example of selective reduction of conjoined twins by thermocoagulation.

Adult↗
PubMed1998

A genome-wide search for chromosomal loci linked to mental health wellness in relatives at high risk for bipolar affective disorder among the Old Order Amish.

Bipolar affective disorder (BPAD; manic-depressive illness) is characterized by episodes of mania and/or hypomania interspersed with periods of depression. Compelling evidence supports a significant genetic component in the susceptibility to develop BPAD. To date, however, linkage studies have attempted only to identify chromosomal loci that cause or increase the risk of developing BPAD. To determine whether there could be protective alleles that prevent or reduce the risk of developing BPAD, similar to what is observed in other genetic disorders, we used mental health wellness (absence of any psychiatric disorder) as the phenotype in our genome-wide linkage scan of several large multigeneration Old Order Amish pedigrees exhibiting an extremely high incidence of BPAD. We have found strong evidence for a locus on chromosome 4p at D4S2949 (maximum GENEHUNTER-PLUS nonparametric linkage score = 4.05, P = 5. 22 x 10(-4); SIBPAL Pempirical value <3 x 10(-5)) and suggestive evidence for a locus on chromosome 4q at D4S397 (maximum GENEHUNTER-PLUS nonparametric linkage score = 3.29, P = 2.57 x 10(-3); SIBPAL Pempirical value <1 x 10(-3)) that are linked to mental health wellness. These findings are consistent with the hypothesis that certain alleles could prevent or modify the clinical manifestations of BPAD and perhaps other related affective disorders.

Adult↗
PubMed1998

Glycated haemoglobin and cardiovascular risk factors in Chinese subjects with normal glucose tolerance.

Increased plasma glucose concentration is a predictive factor for mortality in both diabetic and non-diabetic subjects. Although glycated haemoglobin (HbA1c) is a useful index of mean blood glucose concentrations over the preceding 1 to 3 months, there are few data regarding its relationship to cardiovascular risk. We have examined the relationship between HbA1c and cardiovascular risk factors in 1280 subjects with normal glucose tolerance. Based on HbA1c tertiles (tertile 1: n = 427, 262 men and 165 women, HbA1c level: 2.9-4.7% in men and 3.2-4.2% in women; tertile 2: n = 426, 261 men and 165 women, HbA1c level: 4.7-5.1% in men and 4.2-4.6% in women; tertile 3: n = 427, 262 men and 165 women, HbA1c level: 5.1-6.7% in men and 4.6-6.9% in women), increasing HbA1c was associated with increasing age, blood pressure, waist-hip ratio, fasting and 2-h plasma glucose, 2-h insulin, cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and urate concentrations. When age and sex were included as covariates, increasing HbA1c remained associated with increasing fasting and 2-h plasma glucose, 2-h insulin, total cholesterol, and low-density lipoprotein cholesterol concentrations. These findings emphasize the importance of hyperglycaemia, as reflected by HbA1c, as a continuum in the evaluation of cardiovascular risk. Furthermore, these findings support the hypothesis that cardiovascular disease risk commences with rising glucose concentrations before 'conventionally-defined' glucose intolerance occurs.

Adult↗
PubMed1998

Development of a radiolabeled ATP assay for carboxylic acid:CoA ligases and its use in the characterization of the xenobiotic carboxylic acid:CoA ligases of bovine liver mitochondria.

A radiolabeled ATP assay was developed for measuring carboxylic acid:CoA ligase activity. The assay was designed to measure the formation of [gamma-33P]pyrophosphate from [gamma-33P]ATP in the course of the reaction. The assay was linear with protein concentration, and rates as low as 1 pmol/min were measurable. Rates determined with this assay were in agreement with rates determined with [14C]carboxylic acids. The assay was used to characterize the substrate specificity of the XL-I, XL-II, and XL-III ligases from bovine liver mitochondria. Forty carboxylic acids were tested for activity. The enzymes differed in their substrate specificities with XL-I and XL-II being the most similar and XL-III having the broadest specificity. This study has uncovered 19 new carboxylic acids that are substrates for these enzymes.

Adenosine Triphosphate↗
PubMed1998

Determination of the sequence of the arylacetyl acyl-CoA:amino acid N-acyltransferase from bovine liver mitochondria and its homology to the aralkyl acyl-CoA:amino acid N-acyltransferase.

The arylacetyl acyl-CoA:amino acid N-acyltransferase was previously purified to homogeneity from bovine liver mitochondria, and partial sequences were obtained for peptides generated by cyanogen bromide cleavage of the enzyme. One of these sequences was used to design an oligonucleotide probe that was utilized to screen a bovine liver cDNA library. Several clones were isolated and sequenced, and the sequence is given. The cDNA contains 346 bases of 5'-untranslated region and 439 bases of 3' untranslated region. The cDNA codes for an enzyme containing 295 amino acid residues. The sequence gives a molecular weight for the enzyme of 38,937, which is larger than that previously estimated for the functional enzyme, which suggests the existence of ca. 5 kDA of signal peptide. The molecular weight of the enzyme was slightly lower than that of the aralkyltransferase, which was previously determined to be 39,229. Comparison of this sequence with that which we previously obtained for the aralkyltransferase indicated that the coding regions were of identical length and that the sequences were 78% homologous. However, the 5' and 3' untranslated regions had less than 29% homology. The derived amino acid sequences were 71% homologous. This high homology indicates a common origin for the two enzymes. There are, however, significant differences in amino acid compositions, and these are discussed.

Acetyltransferases↗
PubMed1998

Lack of an association between a dopamine-4 receptor polymorphism and attention-deficit/hyperactivity disorder: genetic and brain morphometric analyses.

Although the etiology of attention-deficit/hyperactivity disorder (ADHD) is likely multifactorial, family, adoption, and twin studies suggest that genetic factors contribute significantly. Polymorphisms of the dopamine 4 receptor (DRD4) affect receptor binding, and one allele with seven tandem repeats in exon 3 (DRD4*7R) has been associated with ADHD. We examined this putative association in 41 children with severe ADHD and 56 healthy controls who were group matched for ethnicity and sex. The frequency of the DRD4*7R allele did not vary by diagnosis (0.220 vs 0.205 in patients and controls, respectively). Behavioral and brain anatomic MRI measures, previously found to discriminate patients from controls, did not differ significantly between subjects having and those lacking a DRD4*7R allele. These data do not support the reported association between DRD4*7R and the behavioral or brain morphometric phenotype associated with ADHD.

Alleles↗
PubMed1998

Nutritional status of elderly Chinese vegetarians.

AIM: To study the nutritional status of elderly Chinese vegetarians. SUBJECTS AND METHOD: Dietary intake (using the 24-h recall method), anthropometric indices and some nutritional laboratory parameters were studied in 131 elderly Chinese vegetarian women with a mean age of 81 years. Data from age- and sex-matched omnivore subjects from previous elderly surveys were used for comparison. RESULTS: Total energy, fat and protein calorie, thiamine, riboflavin and niacin intakes were lower in vegetarians than in non-vegetarians, while carbohydrate calorie, calcium, potassium, retinol equivalent and ascorbic acid intakes were higher. The 25th, 50th and 75th percentile for total body fat were lower and those for corrected arm muscle area were higher in vegetarians. Both urinary Na/Cr and K/Cr ratios were higher but the Na/K ratio was similar to that in non-vegetarians, as were mean systolic and diastolic blood pressures. Serum total cholesterol was lower, while serum triglyceride concentration was similar. The mean haemoglobin level was lower in vegetarians, the prevalence of anaemia being 30%, with deficiencies in B12 and/or iron accounting for 64% of the anaemia, compared with only 30% in non-vegetarians. Serum B12 concentration below the reference range occurred in 54% of the vegetarian subjects. Vegetarians also had a lower prevalence of a history of ischaemic heart disease; however, the prevalence of smoking was also lower. CONCLUSION: While the Chinese vegetarian diet may result in a favourable risk-factor profile for ischaemic heart disease, it is deficient in many B vitamins and gives rise to a high frequency of nutritional anaemias.

Aged↗
PubMed1998

Mycobacterial lymphadenitis in eastern Sydney.

BACKGROUND: There has been a resurgence of tuberculosis (TB) in the developed world, especially extrapulmonary manifestations, of which lymphadenitis is the most common. We reviewed all cases of mycobacterial lymphadenitis notified in the eastern suburbs of Sydney from 1989 to 1996. AIMS: To review all cases of mycobacterial adenitis in eastern Sydney. METHODS: This was a retrospective review of the medical records of 54 patients (aged 1.2 to 84 years), recruited from all notifications of TB presenting as lymphadenitis at Prince of Wales, Sydney Children's and St Vincent's Hospitals. RESULTS: There were two distinct groups: Group 1, patients with Mycobacterium tuberculosis (MTB), n = 37 (68.5%), Group 2, patients with atypical mycobacteria, n = 17 (31.5%). For Group 1, 83.3% were foreign born and 18.9% were positive for the human immunodeficiency virus (HIV). Disease involved single node groups in 73% (the cervical chain was involved in 70.1%). Complete resolution of lymphadenopathy at conclusion of treatment occurred in 73.1%. Outcome was not documented in 13.5%, of the rest; 83.8% completed treatment; 2.7% were lost to follow up before treatment concluded; 2.7% were still being seen at the time of writing and 10.8% died within six months of treatment starting (all were HIV positive). HIV positive patients had more diffuse disease. Group 2 were all Australian born. They comprised children less than six years who were all HIV negative and adults (aged 30-55 years) who were all HIV positive. The children were all treated surgically with 80% having complete resolution of their modes. Those adults with HIV had a mortality of 83.3% during treatment. CONCLUSIONS: In eastern Sydney lymphadenitis caused by MTB in the HIV negative population is mostly seen in those who are immigrants. Our large proportion of HIV positive patients tended to have diffuse disease and a high mortality. The reporting of outcomes was poor and in a greater than expected number of outcome and follow up were inadequately documented.

AIDS-Related Opportunistic Infections↗
PubMed1998

The reproducibility and usefulness of the oral glucose tolerance test in screening for diabetes and other cardiovascular risk factors.

We examined the reproducibility of oral glucose tolerance tests (OGTT) using the World Health Organization criterion in 212 Chinese subjects (male 149, female 63) who underwent two 75 g OGTTs within a 6-week period. The overall reproducibility was 65.6% (139/212) of which 74 subjects had normal glucose tolerance, 24 had diabetes and 41 had impaired glucose tolerance (IGT) on two occasions. The subjects were divided into three groups [group 1: normal OGTTs on both occasions (n = 74); group 2: one abnormal OGTT (either diabetes or IGT (n = 51); group 3: 2 abnormal OGTTs (n = 87)]. Subjects in group 1 were younger, had lower blood pressure, body mass index (BMI), waist-to-hip ratio (WHR), fasting and 2 h plasma insulin levels, triglyceride, very-low density lipoprotein and apolipoprotein-B concentrations than both groups 2 and 3. Group 2 had similar characteristics as group 3 except for a lower glycated haemoglobin (HbA1c), fasting and 2 h plasma glucose during the two OGTTs. With receiver operating characteristic curve (ROC) analysis, a HbA1c of 5.3% gave an optimal sensitivity of 70.7% and specificity of 74.3% to predict diabetes as defined by a 2 h plasma glucose value > or = 11.1 mmol/L in the first OGTT. Of the 212 subjects, 73 had HbA1c > or = 5.3%. The reproducibility of OGTT was 56.2% for these 73 subjects. With ROC analysis, a BMI of 25 kg/m2 gave an optimal sensitivity of 53.7% and specificity of 56.7% to predict diabetes. For the 36 subjects with BMI > or = 25 kg/m2, the reproducibility of OGTT was 58.3%. Similarly, for the 140 subjects with WHR > or = 0.9, the reproducibility of OGTT was 57.9%. These findings confirmed the poor reproducibility of OGTT which was not improved even amongst subjects with high HbA1c, BMI or WHR. Furthermore, subjects with one abnormal OGTT, whether reproducible or not, had a higher cardiovascular risk profile compared to subjects who had two normal OGTTs.

Adult↗
PubMed1997

Pullback atherectomy with the Arrow-Fischell atherectomy device.

The Arrow-Fischell pullback atherectomy catheter is designed to circumferentially debulk and retrieve coronary atheroma. We performed pullback atherectomy before balloon angioplasty or stenting in 41 patients. The device crossed the target lesion in 38 (93%) and obtained tissue in 36 (88%). All procedures were completed successfully and without myocardial infarction, emergency cardiac surgery, or death. Complications included major spasm in 8 patients, postprocedural abrupt closure in 1, and otherwise uncomplicated arterial perforation in 2. Pullback atherectomy can be performed relatively safely, but is more difficult than balloon angioplasty, obtains less tissue than directional atherectomy, and is associated with significant limitations.

Aged↗
PubMed1997

Characterization of guanidine transport in human renal brush border membranes.

PURPOSE: Organic cation transporters in the renal proximal tubule are important in the secretion of many clinically used drugs and their metabolites. The goal of this study was to determine the mechanisms of guanidine transport in human kidney. METHODS: Brush-border membrane vesicles were prepared from donor human kidneys deemed unsuitable for renal transplantation. RESULTS: Uptake of [14C]-guanidine (50 microM) in the vesicles, as determined by rapid filtration, was significantly greater in the presence of an outwardly-directed proton gradient, at all early time points, than in the absence of the gradient. Proton-stimulated uptake of [14C]-guanidine at 30 sec (32.0 +/- 1.24 pmol/mg protein) was significantly inhibited by a number of organic cations including 5 mM unlabeled guanidine (14.8 +/- 1.84 pmol/mg protein) and 5 mM MIBA (9.14 +/- 3.80 pmol/ mg protein), but not by 5 mM TEA (28.4 +/- 5.67 pmol/mg protein). Guanidine, but not TEA, trans-stimulated [14C]-guanidine uptake. Conversely, TEA, but not guanidine, trans-stimulated [14C]-TEA uptake in the vesicles. The proton-dependent transport of guanidine was characterized by a Km of 3.52 +/- 0.42 mM (SE) and a Vmax of 34.6 +/- 8.64 pmol/mg protein/sec (SE). CONCLUSIONS: These results demonstrate that guanidine transport in human renal brush border membrane vesicles is stimulated by a proton gradient. Evidence was obtained suggesting that the transporter for guanidine is distinct from the previously described organic cation proton antiporter for TEA.

Biological Transport↗
PubMed1997

The reliability of upper limb anthropometry in older Chinese people.

OBJECTIVE: To evaluate the validity of the Durnin-Womersley equations and to derive our local predictive equations for body fat from upper limb skinfold thicknesses in older Chinese people in Hong Kong. To evaluate the validity of mid-arm circumference and corrected arm muscle area in predicting lean tissue mass in the same population. DESIGN: Comparison of fat percentages predicted by Durnin-Womersley (D-W) equations with those estimated by Dual energy X ray absorptiometry (DXA). Predictive equations derived from regression between upper limb skinfold thicknesses and fat percentages estimated by DXA were similarly evaluated in internal and external validation groups. Mid-arm circumference (MAC) and corrected arm muscle area (CAMA) were correlated with the limb lean tissue mass, body lean tissue mass and fat percentage. SUBJECTS: 354 female and 263 male, apparently well, community dwelling subjects, aged 69-82 y; of which 40 subjects of each sex were randomly selected from the study population for internal validation of the local predictive equations; 60 female and 33 male hospital medical outpatients, aged 61-87 y, were recruited for external validation. MEASUREMENTS: Triceps and biceps skinfold thicknesses, mid-arm circumference, body mass index, fat percentages, limb and whole body lean tissue masses estimated by Hologic QDR-2000 bone densitometer. RESULTS: Fat percentages calculated by D-W equations were significantly different from those estimated by DXA (average difference -2.4 (s.d. 4.8)% and +2.1 (5.2)% in females and males respectively). The corresponding differences for our local predictive equations were not significant (-0.9 (4.7)% and -0.5 (5.0)% in females and males respectively). There was a trend of under-estimation of body fat with increasing fatness. In the hospital medical outpatients, there was a significant difference between fat percentages predicted by our equation and those by DXA in female (-2.9(5.3)%), but not in male (+0.3(4.3)%) subjects. In males, MAC correlated with limb and body lean tissue masses as well as with fat percentage (r = 0.60, 0.68, 0.65 respectively). CAMA correlated similarly well with lean tissue masses but was more independent of fat percentage (r = 0.61, 0.65, 0.44 respectively). In females, both MAC and CAMA correlated poorly with limb and body lean tissue masses. Moreover, MAC correlated well with fat percentage (r = 0.80). CONCLUSION: Upper limb skinfold thicknesses measurement is a valid means of predicting body fat in older Chinese people. Local predictive equations were more reliable that D-W equations. They were, however, subject to errors at the extreme ends of body fatness and in the presence of disease. In older females, MAC and CAMA were not reliable in predicting lean tissue mass, but MAC could be used to predict fat percentages. In older males, CAMA was more reliable than MAC in predicting lean tissue mass.

Absorptiometry, Photon↗
PubMed1997

Simple anthropometric indexes and cardiovascular risk factors in Chinese.

OBJECTIVE: Obesity is a major public health problem due to its associations with multiple cardiovascular risk factors. Although there are sophisticated methods, such as imaging, to document total body fat and its distributions, anthropometric measurements remain important in clinical practice. We examined the relationships between cardiovascular risk factors and the three commonest anthropometric measurements for obesity, body mass index (BMI), waist-hip ratio (WHR) and waist circumference (WC), in Hong Kong Chinese subjects. DESIGN AND SETTING: The data are obtained from a prevalence survey for glucose intolerance and lipid abnormality in a representative Hong Kong Chinese working population. All employees from a public utility company and a regional hospital were invited to participate. SUBJECTS: There were 1513 subjects (910 men and 603 women, mean age +/- s.e.m.: 37.5 +/- 0.2 y). All of them had no significant past medical history. MEASUREMENTS: BMI, WHR and WC of the 1513 subjects were assessed for their relationships with various cardiovascular risk factors. These include blood pressure, fasting and 2 h plasma glucose and insulin, glycated haemoglobin, total cholesterol, triglyceride, high density and low density lipoprotein cholesterol, and urine albumin concentration. RESULTS: After age adjustment, all three anthropometric indexes were significantly correlated with the major cardiovascular risk factors in both men and women. When BMI, WHR and WC were analysed according to quartiles, there was a significant trend for blood pressure, plasma triglyceride, fasting and 2 h plasma glucose and insulin to increase, and high density lipoprotein cholesterol to decrease, with increasing obesity after adjustment for age and smoking. Using stepwise regression analysis with the three indexes as independent variables, most of the variance in blood pressure, plasma lipid, insulin, glucose and urinary albumin concentration were explained either by WC or WHR. In women, BMI was the main explanatory variable for reduced high density lipoprotein cholesterol. CONCLUSIONS: In Hong Kong Chinese, BMI, WHR and WC provide important information in assessing cardiovascular risks. In men, central adiposity as reflected by WC and to some extent, WHR, explained most of the variance in blood pressure, plasma glucose, lipid, insulin and albuminuria. In women, all three indexes reflecting general and central obesity contribute to the variance in these risk factors.

Adult↗