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Biomedical subjects

L Chan

Publications and source records attributed to L Chan.

At least 433 records · Page 24Linked to original sources
PubMed1985

Translational control of the circadian rhythm of liver sterol carrier protein. Analysis of mRNA sequences with a specific cDNA probe.

The striking changes in amount of rat liver SCP (sterol carrier protein) during a 24-h dark-light cycle are due to alterations in the relative synthetic rate of SCP. However, functional SCP mRNA, measured by a cell-free translational assay, does not fluctuate in the dark-light cycle. Since cell-free translational assays do not always reflect the actual abundance of an mRNA molecule, a specific cDNA hybridization assay was used to directly quantitate SCP mRNA sequences. The cDNA probe was selected from a rat liver library by hybridization to a mixture of synthetic oligonucleotides containing a portion of the sequence of SCP mRNA. The relative amount and size distribution of the SCP mRNA species (approximately 700-800 nucleotides) does not change during the diurnal cycle. To explore possible mechanisms of this translational control, the polysomal distribution of SCP mRNA was compared at the maximum and minimum points of SCP synthesis. No significant amounts of SCP mRNA were present in nonpolysomal ribonucleoprotein particles. Furthermore, no alteration in the relative level of SCP mRNA associated with polysomes or in polysome size occurs at the maximum and minimum points of SCP synthesis. Thus, changes in total SCP mRNA levels or its polysomal distribution cannot account for the diurnal variation in SCP synthesis.

Animals↗
PubMed1985

Human liver fatty acid binding protein cDNA and amino acid sequence. Functional and evolutionary implications.

Human liver fatty acid binding protein (L-FABP) cDNA clones were identified in a liver cDNA library. The two longest clones were completely sequenced. The nucleotide sequence predicts a protein of 127 amino acid residues. Identity of the clones was confirmed by limited amino acid sequence analysis of purified human L-FABP peptides and Edman degradation of radiolabeled in vitro translated FABP. Statistical analysis of the amino acid and mRNA sequences of human L-FABP, rat L-FABP, rat intestinal (I-) FABP, and mouse 422 protein indicates that the human and rat L-FABPs are highly homologous and that L-FABP and I-FABP diverged a long time ago (approximately 650-690 million years ago), although they are more closely related to each other than either of them is to 422 protein. Secondary structure predictions from the primary sequence of human and rat L-FABP reveal a region (residues 12-30) that might be the putative fatty acid binding domain of the two L-FABPs. Knowledge of the primary amino acid sequence of L-FABP and possible functional domains will be pivotal in further defining and understanding the mechanism of ligand binding and transfer by this protein.

Amino Acid Sequence↗
PubMed1985

A novel monoclonal antibody BI-3C5 recognises myeloblasts and non-B non-T lymphoblasts in acute leukaemias and CGL blast crises, and reacts with immature cells in normal bone marrow.

A MCA raised against the human acute myelogenous leukaemia cell line KG1 reacted with only KG1 among 26 haematopoietic cell lines covering the major lineages. It reacted with early myeloid (M1/2), 1 of 2 acute myelomonocytic (M4) and most non-B non-T leukaemias, including blast crises of CGL. Among M1-AML cells, both MPO+ and MPO- blasts were BI-3C5+. Blasts in 3 Tdt+ M1-AMLs were simultaneously BI-3C5+. BI-3C5 reacted with 4% cells in normal BM, many of which were histologically recognisable as myeloid precursors. 8-15% of BI-3C5+ cells in BM were simultaneously Tdt+, and all were weakly Ia antigen+. BI-3C5 was unreactive with all peripheral leucocytes, with M3 and M5 AMLs, with lymphoid and myeloid leukaemias of "mature" phenotype (T-ALL, B-ALL, CLL, CGL) and with non-haematopoietic cell lines. BI-3C5 precipitated a 120K moiety from 125I-labelled KG1 membranes. It was not blocked by J5 anti-cALLA. The potential use of BI-3C5 in the classification of acute leukaemias is discussed.

Animals↗
PubMed1985

Molecular cloning and expression of partial cDNAs and deduced amino acid sequence of a carboxyl-terminal fragment of human apolipoprotein B-100.

Apolipoprotein (apo) B-100 cDNAs were identified in a human liver cDNA library cloned in the expression vector lambda gt11. The beta-galactosidase-apoB-100 fusion protein was detected by two independently produced low density lipoprotein polyclonal antisera and by three apoB-100 monoclonal antibodies that crossreact with apoB-74. It was not recognized by two apoB-100 monoclonal antibodies that crossreact with apoB-26. The longest clone, lambda B8, was completely sequenced. It contains a 2.8-kilobase DNA fragment containing the codons for the carboxyl-terminal 836 amino acid residues of apo-B-100, as well as the 3' untranslated region of apoB-100 mRNA. We have thus mapped apoB-74 to the carboxyl-terminal portion of apoB-100. The deduced amino acid sequence of the cloned DNA matches the sequences of 14 apoB-100 peptides determined in our laboratory. Minor differences in amino acid sequence were noted in three of the peptides, suggesting polymorphism of apoB-100 at the protein and DNA levels. Secondary structure predictions reveal an unusual pattern for apolipoproteins, consisting of beta-structure (24%), alpha-helical content (33%), and random structure (30%). Ten amphipathic helical regions of 10-24 residues were identified. This carboxyl-terminal fragment of apoB-100 is considerably more hydrophobic than other apolipoproteins with known structure. Its lipid binding regions might include stretches of highly hydrophobic beta-sheets as well as amphipathic helices. Our findings on apoB structure might be important for understanding the role of apoB-100-containing lipoproteins in atherosclerosis.

Amino Acid Sequence↗
PubMed1985

The effect of verapamil on renal function after warm and cold ischemia in the isolated perfused rat kidney.

The potential usefulness of verapamil, a calcium channel blocker to renal allograft preservation, was investigated using the isolated perfused rat kidney. Two models of ischemic injury were used. In the first model, rat kidneys were exposed to 40 min of 37 degrees C ischemia on the perfusion circuit. Addition of verapamil in doses of 2.5, 5, and 100 microM concentration to the perfusate significantly improved inulin clearance (Cin) and total sodium absorption (TNa) in the hour of reperfusion following ischemia. Regeneration of adenosine triphosphate (ATP) and total adenine nucleotide TAN levels during reperfusion following warm ischemia were also significantly higher in verapamil-treated kidneys. In the second model, rat kidneys were flushed in situ with Collins C2 solution and stored at 0 degrees C for 8 hr. After this period of cold ischemia, they were perfused on a perfusion circuit with perfusion media. Verapamil 2.5 microM was absent from both flush and perfusate (control), or added to just the flush, both the flush and perfusate, or just the perfusate. Addition of verapamil to the flush or the flush and perfusate significantly improved Cin, urine flow rate (V) and TNa during reperfusion, compared with control. Addition of verapamil to just the perfusate did not effect Cin, TNa, or V but did significantly increase RPF. These findings suggest the verapamil may protect against organ damage occurring during both warm and cold ischemia in the absence of any systemic effects and thus may be useful for renal allograft preservation.

Adenine Nucleotides↗
PubMed1985

The (4;11) translocation in acute leukaemia of childhood: the importance of additional chromosomal aberrations.

Case reports of four girls and one boy with acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML) and t(4;11) are presented. The incidence of t(4;11) ascertained at diagnosis in ALL was 2.6% and in AML 5.3%. Four of the children were under 2 years and one was 11 years at diagnosis. Leucocyte counts above 71 X 10(9)/l and liver, spleen and node enlargement were found in all cases. Blasts of the four cases tested at diagnosis were negative to the c-ALL antigen and either TdT+ (ALL) or TdT- (AML M1). Maximum survival was less than 8 months. Additional chromosomal change was found at diagnosis in two cases and in relapse in a third. In the case of AML t(4;11) (q21;p15) was present as a second translocation. Additional numerical changes, in these and other reported cases, included + 6, commonly found in ALL, +8, +19, more often reported in AML. It is suggested that additional chromosomal changes in these cases support cytochemical and surface marker evidence that t(4;11) has a pluripotent target cell, similar to that of the Philadelphia translocation.

Adolescent↗
PubMed1985

Insulin secretory capacity in Singapore diabetic subjects.

The determination of serum C-peptide has been found to be a sensitive indicator of endogenous insulin secretion, and serves to define diabetic patients who require insulin therapy i.e., insulin-dependent (Type I, IDDM) and those non-insulin dependent (Type II, NIDDM). The aim of our study is to establish the types of diabetes mellitus with C-peptide measurement in a group of diabetic subjects on different modes of therapy. Eighty-eight diabetic patients (60 males, 28 females) were studied. Thirty-four were on insulin (age 40 +/- 2 years; means +/- SEM), 35 on oral agents (54 +/- 1 years), and 19 on diet alone (46 +/- 3 years). Twenty healthy subjects (10 males, 10 females) serve as normal controls (37 +/- 3 years). Blood samples for serum C-peptide and blood glucose estimations were obtained after an overnight fast and one hour after a 75 grams oral glucose load. Fasting C-peptide levels obtained for the various groups were: 0.62 +/- 0.07 (nmol/L, means +/- SEM) (normal), 0.16 +/- 0.02 (insulin), 0.79 +/- 0.06 (oral), 2.15 +/- 0.15 (diet). The C-peptide values after oral glucose were 1.80 +/- 0.20 (normal), 0.23 +/- 0.05 (insulin), 1.72 +/- 0.02 (oral), 2.15 +/- 0.15 (diet). Both the fasting and post-glucose C-peptide concentrations were significantly lower (p less than 0.001) in the insulin group compared to the normals, whereas values for the diet and oral groups were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Infections in diabetes with special reference to diabetics in Singapore.

Most physicians believe that the diabetic patient is predisposed to infections and that infections complicate the control of the diabetes. Despite the lack of scientific proof, certain infections (such as tuberculosis, bacteriuria in females, malignant external otitis, rhinocerebral mucormycosis, emphysematous cholecystitis, emphysematous pyelonephritis, acute papillary necrosis etc) are widely regarded to be associated with the diabetic. Foot infections, infections of the respiratory tract and the urinary tract are very important in the diabetic. The reasons why diabetics are susceptible to infections are unclear: although the production of humoral antibody appear intact, defective function of the polymorphonuclear leucocytes has been demonstrated. Successful treatment of infections in the diabetic requires early and exact diagnosis, the exhibition of the correct antimicrobials, the treatment of the diabetic state and associated disorders and prompt surgical intervention where required. Good control of blood glucose in diabetic patients is a desirable goal in the prevention of certain infections and to ensure maintenance of normal host defense mechanisms that determine resistance and response to infection.

Abscess↗
PubMed1985

The current status of magnetic resonance spectroscopy--basic and clinical aspects.

Magnetic resonance (MR) spectroscopy is a well-established method of chemical analysis in which the magnetic moment and radio-frequency emission characteristics of each atom and molecule are subjected to a high-intensity magnetic field. This method is now established as a noninvasive way of studying metabolism in vivo. With the development of wide-bore, high field (1.5 tesla or above) magnets, studies of human metabolism are now possible. Most metabolic MR spectroscopic studies have focused on the phosphorus 31 nucleus. Spectra can be obtained from phosphorylated metabolites such as adenosine triphosphate, phosphocreatine, inorganic phosphate and sugar phosphate. In addition, (31)P nuclear magnetic resonance spectra can provide a continuous monitor of the intracellular pH. The other nuclei used for metabolic studies are hydrogen 1, carbon 13 and, to a lesser extent, sodium 23. Much additional research is required before an assessment can be made of the extent to which MR spectroscopy can be used to provide diagnostically useful information. The noninvasive biochemical approach to human metabolism may involve as-yet-undiscovered metabolic features of disease processes.

Brain↗
PubMed1985

Protein-sparing diet for severely obese adolescents: design and use of an equivalency system for menu planning.

When severe, obesity in adolescence demands effective treatment, thus justifying use of a protein-sparing, low-energy diet for periods of 3 to 4 months. When properly planned and supervised, this diet is safe and effective, even if only to maintain a functional body weight. The regimen used at the Hospital for Sick Children, Toronto, provides 2.0 to 2.5 gm protein per kilogram ideal body weight, plus adequate fluid and nutrient supplements. The amounts of meat, poultry, and fish that supply this allocation of protein are determined using a protein equivalency system developed for the diet. The system allows both dietitians and patients to plan meals that minimize energy intake while maintaining protein adequacy and dietary variety. With prolonged use of the diet, limited carbohydrate may be added in the form of selected vegetables measured using a similar carbohydrate equivalency system. Recent use of the diet for 21 patients, 8 to 20 1/2 years old and averaging 211% ideal body weight, resulted in acceptable weight control.

Adolescent↗
PubMed1985

A comparative study of three methods of glycosylated haemoglobin measurements.

This report summarizes our experience with 3 methods of glycosylated haemoglobin (HbA1) determinations. Glycosylated haemoglobin levels were determined using microcolumn chromatography (Boehringer Mannheim), agar gel electrophoresis (Corning GlytracTM) and colorimetry. The HbA1 values for 40 normal controls using chromatography, electrophoresis and colorimetry were 7.31 +/- 0.67 (+/- 1 S.D.), 7.98 +/- 0.81 and 8.54 +/- 1.09% respectively. The intra-assay coefficients of variation were 3.3, 4.5 and 2.0% respectively. There were also good correlations among the 3 methods of HbA1 measurements: electrophoresis vs chromatography, r = 0.91 (p less than 0.001) and electrophoresis vs colorimetry, r = 0.84 (p less than 0.001). Similarly, all 3 methods correlated well with the fasting and mean grouped blood glucose values (p less than 0.001). The chromatographic method is precise and well suited for small sample analysis. The colorimetric method, although the least expensive is labour intensive, suitable only for large batch analysis and in situations where results are not required immediately. The electrophoresis method is also precise, the least labour intensive and well suited for small and large volume laboratories. This study showed that since all 3 methods demonstrated similar precision and good correlation with fasting and grouped blood glucose values, the method of choice will depend on the requirements and support facilities of the individual laboratories.

Blood Glucose↗
PubMed1985

Home blood glucose monitoring, glycaemic control and diabetic complications.

The aim of this study was to evaluate the effect of home blood glucose monitoring on diabetic complications and metabolic control. Forty Chinese and Indian patients participated in the Diabetic Society of Singapore National Home Blood Glucose Monitoring (HBGM) Programme. The clinical progress, the blood glucose and glycosylated haemoglobin concentrations, and the platelet aggregation of the aforementioned patients were studied over a 6-month period; the results were compared with those from a matched, albeit smaller, control group of 18 diabetic patients who were on treatment but not in the HBGM programme. At the end of the six month period, three patients in the control group showed clinical deterioration of peripheral neuropathy in contrast to one patient on HBGM. Due to the small number of patients, the difference in the findings was not statistically significant. Patients on HBGM demonstrated significant improvement in mean grouped blood glucose profile values, 135 +/- 8 to 118 +/- 5 mg/dl, p less than 0.01, and glycosylated haemoglobin levels, 10.3 +/- 0.4 to 9.3 +/- 0.3%, p less than 0.01. The platelet aggregability was unchanged. In contrast, patients in the control group developed a significant increase in platelet aggregation (30 +/- 4% to 37 +/- 5%, p less than 0.05), although the blood glucose and glycosylated haemoglobin concentrations were not significantly altered. This study demonstrated that patients on a six-month HBGM programme were able to achieve improved glycaemic control associated with a trend towards decreased deterioration of diabetic neuropathy and platelet aggregability.

Adult↗
PubMed1984

Human apolipoprotein A-II: nucleotide sequence of a cloned cDNA, and localization of its structural gene on human chromosome 1.

Using the technique of oligonucleotide hybridization, we have isolated two dscDNA clones to human apolipoprotein A-II. One of the clones (pAII-1) has been completely sequenced. It has 433 nucleotides which includes a poly A tail of 10 adenylic acid residues, all the coding and 3'-non-translated regions of the mRNA and part of the 5'-non-translated region. The amino acid sequence derived from the cDNA clone includes 100 amino acids (including the 23 amino acid prepropeptide) which is very similar to the sequence reported by Brewer et al. (Proc. Natl. Acad. Sci. USA 69, 1304-1308). [32P]-labeled pAII-1 was used as a probe in chromosome mapping studies to detect the human apoAII structural gene sequence in human-Chinese hamster cell hybrids. Southern blot analysis of 10 hybrids localized the gene to human chromosome 1.

Amino Acid Sequence↗
PubMed1984

Oral potassium chloride and amiloride in hydrochlorothiazide-induced potassium loss.

To compare the effect of amiloride with that of oral potassium chloride (KCl) in hypokalemia, metabolic balance studies were carried out in hospitalized subjects with mild hypertension without edema who developed negative potassium balance after 4 days on hydrochlorothiazide (HCTZ). Subjects' diets contained measured amounts of sodium and potassium. While HCTZ treatment continued, oral preparations of either KCl solution or amiloride was added for 5 additional days. Potassium balance in the KCl-treated group further decreased by -44.9 +/- 32.3 mEq K+, while subjects on amiloride went into positive balance that averaged +51.7 +/- 24.1 mEq K+. Hypokalemia after HCTZ did not respond to KCl, while K+ levels rose from 3.32 +/- 0.22 to 3.67 +/- 0.26 mEq/l after amiloride.

Administration, Oral↗
PubMed1984

Localization of the structural gene for human apolipoprotein A-I on the long arm of human chromosome 11.

Apolipoprotein A-I (apo A-I), the major apolipoprotein in human high density lipoproteins, is involved in the disease atherosclerosis. Cloned apo A-I cDNA (pA1-3) was used as a probe in chromosome mapping studies to detect the human apo A-I structural gene sequence in human-Chinese hamster cell hybrids. Southern blot analysis of 13 hybrids localized the gene to human chromosome 11. Confirmation of the chromosomal assignment was obtained by analysis of a hybrid (J1) containing a single human chromosome, no. 11. Regional mapping was achieved by using deletion subclones of J1 that localized the human apo A-I structural gene to the region 11q13 leads to qter. Since the human apolipoprotein C-III (apo C-III) structural gene is closely linked to apo A-I, it can be assigned to the same region on the long arm of chromosome 11. By extension of methods previously described, it now appears possible to carry out fine-structure analysis of this and related gene regions on chromosome 11 and to study the biochemical concomitants of these genes and of genes on other chromosomes for analysis of their role in atherosclerosis.

Animals↗
PubMed1984

Evidence for two distinct mechanisms of resistance to polymyxin B in Pseudomonas aeruginosa.

Pseudomonas aeruginosa H181 and H185 are resistant to initial exposure to polymyxin B and continue to grow in its presence. Growth of the strains in the presence of 50 U of polymyxin B per ml was characterized by a doubling time of 120 min, whereas the doubling time in the absence of polymyxin was 60 min. Growth for two generations in the presence of polymyxin caused a 23 to 31% increase in lipopolysaccharide content. In addition, a marked increase in susceptibility to the detergents sodium deoxycholate, Triton X-100, and sodium dodecyl sulfate was observed. The resistant mutants had a small but significant reduction in their levels of dodecanoic acid as compared with the parent strain; however, this was the only consistent alteration observed in levels of fatty acids or readily extractable lipids. Polymyxin was fluorescently labeled by coupling to 1-dimethylaminonaphthalene-5-sulfonyl chloride (dansyl chloride). Growth of strains H181 and H185 in the presence of dansylated polymyxin resulted in a stable association between the fluorescent antibiotic and the outer membrane. We postulate that these alterations are part of an adaptive response by the strains to the presence of polymyxin in the growth medium and reflect a resistance mechanism distinct from the mechanism affording polymyxin B resistance when these strains are initially exposed to the antibiotic.

Bacterial Proteins↗
PubMed1984

Acute renal failure due to leptospirosis: clinical features and outcome in six cases.

Six cases of severe leptospiral infection with renal failure are described. Five of the six patients had acute oliguric renal failure requiring dialysis. Renal function recovered over three weeks and by two months all patients had plasma creatinine levels less than 200 mumol/litre. The initial diagnosis of leptospirosis depended on clinical and epidemiological features because serological confirmation was not possible during the first week of the illness. All the patients had either high risk occupations or a history of exposure to external sources of infection. All had fever, myalgia, jaundice and muscle tenderness. Although bilirubin levels were high (greater than 350 mumol/litre in five) the elevations of aspartate transaminase and alkaline phosphatase levels, and prolongations of prothrombin times were relatively slight. Thrombocytopenia occurred in five of the six cases. Leptospira complement fixation tests were weakly positive or negative on admission in five cases but rose to significant levels subsequently. Penicillin treatment resulted in Jarisch-Herxheimer reactions in three cases. The important complications were: upper gastro-intestinal haemorrhage (five cases), thrombocytopenia less than 30 000 platelets/mm3 (four cases), atrial fibrillation (three cases), drowsiness with asterixis (four cases). All six patients were seriously ill and required intensive supportive therapy. All survived.

Acute Kidney Injury↗