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Biomedical subjects

A W Tan

Publications and source records attributed to A W Tan.

At least 19 recordsLinked to original sources
PubMed2005

High-dose intravenous immunoglobulin in the treatment of toxic epidermal necrolysis: a study of ocular benefits.

PURPOSE: To compare acute ocular complications of toxic epidermal necrolysis (TEN) following treatment with high-dose human intravenous immunoglobulin (IVIG) with a historical cohort not treated with IVIG. METHODS: Retrospective, historically controlled study. In all, 10 consecutive patients with TEN (treatment cohort) presenting between 1 July 2001 and 30 June 2002. Totally, 18 consecutive patients with TEN (historical cohort). SettingTan Tock Seng Hospital, Singapore. The treatment cohort received high-dose IVIG (2 g/kg body weight over 2 days). Patients' records were retrospectively reviewed for their demographic characteristics, causative drug, treatment, ocular involvement (if any, as assessed by an ophthamologist), and its severity. The historical cohort comprised patients coded with a diagnosis of TEN (ICD Code 695.1) between 1 July 1995 and 30 June 2001. RESULTS: Nine (90%) of 10 patients treated with IVIG had ocular involvement. Phenytoin was the implicated drug in three (37.5%) patients. Of the nine patients, 1 died of septic shock. Of the eight survivors, IVIG was initiated immediately upon onset of TEN as all the patients were hospitalized by the time of onset of an exanthema. Acute ocular complications were mild in two (25%) (lid oedema or mild conjunctival injection), moderate in four (50%) (pseudomembranes) and severe in two (25%) (nonhealing epithelial defect with visual loss and symblepharon). In total, 10 (55.6%) of 18 patients in the historical cohort with TEN had acute ocular involvement. Two patients died. Ocular involvement in survivors was mild in five (62.5%) cases and moderate in three (37.5%), with no severe cases. CONCLUSIONS: IVIG did not appear to reduce the severity of visually significant ocular complications. Larger studies are needed to confirm this finding.

Acute Disease↗
PubMed2004

A case of nephrogenic fibrosing dermopathy.

INTRODUCTION: Nephrogenic fibrosing dermopathy is a recently recognised fibrosing disorder originally identified as a scleromyxoedema-like cutaneous disease in patients with renal disease. CLINICAL PICTURE: A 45-year-old lady with systemic lupus erythematosus presented with well-defined erythematous, non-tender, indurated plaques on both legs 4 months after haemodialysis for rapidly progressive glomerulonephritis and acute renal failure. Skin biopsy showed dermal fibrosis with increased proliferation of dermal fibroblasts and collagen bundles separated by clefts. There were increased dermal deposits of mucin and an increase in elastic fibres. TREATMENT AND OUTCOME: Haemodialysis was instituted for 2 weeks followed by monthly intravenous cyclophosphamide. Skin lesions remained unchanged 8 months later despite normalisation of renal function. CONCLUSION: Nephrogenic fibrosing dermopathy appears to be a definite new entity in patients with underlying renal insufficiency. Further multi-centre collaborative study is necessary to identify the prevalence, cause, treatment and prognosis of this disorder.

Acute Kidney Injury↗
PubMed2001

Assessment of hypercholesterolemia control in a managed care organization.

To determine the extent of achievement of goal low-density lipoprotein cholesterol (LDL) as defined by National Cholesterol Education Program-Adult Treatment Panel II (NCEP-ATP 11) and American Diabetes Association (ADA) 2000 guidelines, we conducted a retrospective study by integrating data from medical, laboratory, and pharmacy claims databases. Subjects were selected from a 232,000-member staff-model managed care organization consisting of 19 clinics in the Minneapolis-St. Paul, Minnesota, metropolitan area. A total of 124,971 members aged 18 years and older, who had been continuously enrolled from July 1, 1996-June 6, 1998, were included. Outcome measures were the extent of achievement of goal LDL as defined by NCEP-ATP II and the use of antihyperlipidemic drugs for patients with and without diabetes at various levels of risk for coronary heart disease (CHD). Of 124,971 subjects, 6538 had a history of CHD, 1523 of whom met their LDL goal. Of the population with CHD who did not achieve goal, 1141 (43%) missed by over 30 mg/dl; 621 (54%) of these patients were not receiving drug therapy A total of 17,267 had no history of CHD but had two or more risk factors; 3,298 of these achieved their LDL goal. Of those who did not achieve goal, 1,136 (35%) missed by over 30 mg/dl; 897 (79%) of these were not receiving drug therapy A total of 6,586 had a history of diabetes; 1,004 and 2,340 reached an LDL of 100 mg/dl or lower and less than 130 mg/dl, respectively Of those with diabetes who had an LDL greater than 100 mg/dl, 1,276 (49%) missed their goal by over 30 mg/dl; 898 (70%) of these were not receiving drug therapy. Inadequate use of pharmacologic agents plays a significant role in failure to achieve goal LDL for patients with CHD, without CHD, and with diabetes. Analysis of the data based on the new ADA guidelines for LDL demonstrates the need for continued vigilance. Finally, the successful merging of medical, laboratory, and pharmacy claims databases provides a benchmark for other institutions.

Adult↗
PubMed2000

Quantitation of peripheral blood cytomegalovirus DNA for monitoring recurrent cytomegalovirus retinitis in pediatric solid organ transplant recipients.

Cytomegalovirus (CMV) infection is a major concern following solid organ transplantation, especially in the pediatric population who remain at high risk of primary infection. CMV disease leads not only to increased patient and graft morbidity, but also to increased health care costs. This study describes the usefulness of a quantitative CMV polymerase chain reaction (PCR) technique for monitoring peripheral blood CMV DNA in pediatric recipients of kidney and liver allografts who had recurrent CMV retinitis. The incidence of CMV disease in 28 pediatric transplant recipients was 28.6%, one-half of whom developed retinitis. Two of these patients had recurrent retinitis on cessation of anti-viral treatment. A peripheral blood CMV DNA copy number of > or =500/microg of DNA was associated with recrudescence of the retinitis in these patients. We conclude that the measurement of peripheral blood CMV DNA by PCR is a useful tool for the surveillance of disease resolution and recurrence. This is particularly important in patients with CMV retinitis, who may remain asymptomatic for a period of time, despite recurrences.

Adolescent↗
PubMed1999

Obesity, fitness, willingness to communicate and health care costs.

BACKGROUND: Obesity and low levels of physical fitness are independently associated with a variety of diseases and disorders. These conditions are modifiable and affect health care utilization. The degree to which these health risks are modifiable is directly related to the readiness of individuals to change the underlying behaviors. This study analyzes the relationship between health care costs, obesity, physical fitness, and willingness to communicate. In addition, we tested the hypothesis that willingness to communicate is directly associated with an individual's readiness to change behavior. METHODS: Multiple regression was used to estimate the relationship between adverse behavioral health outcomes, willingness to communicate, and annualized health care costs incurred over a period of 33 months before the completion of a health risk assessment survey in an employed population enrolled in a Midwestern managed care organization (N = 8822). RESULTS: High body mass index (BMI), low physical fitness (predicted VO2max), and greater willingness to communicate were directly and significantly (P < 0.05) associated with higher health care costs. Relative to low-risk, annualized health care costs for each of the high-risk factors were 8% higher for BMI (rate ratio, 1.08; 95% confidence interval, 1.01-1.15), 10% higher for low predicted VO2max (rate ratio 1.10, 95% confidence interval, 1.02-1.18), and 22% higher for willingness to communicate (rate ratio, 1.22, 95% confidence interval, 1.14-1.30). The association between these health risks and health care costs was independent of age, sex, age-sex interaction, role-mental and role-physical limitations, and nine chronic conditions. Furthermore, willingness to communicate was directly related to a greater readiness to change behavior. CONCLUSIONS: The prevalence of obesity and low physical fitness is high, and these health risks are directly related to health care costs. Willingness of health plan members to communicate around health improvement opportunities appears greatest among those who incur higher costs, and these patients also have more favorable readiness to change profiles. Effective, proactive population-based health improvement efforts appear to have significant potential for positive economic impact.

Adult↗
PubMed1990

The primary structure of rat liver glycogen synthase deduced by cDNA cloning. Absence of phosphorylation sites 1a and 1b.

The cDNA for rat liver glycogen synthase was isolated by screening a rat liver cDNA library constructed in lambda gt11. The cDNA was 2.4 kilobases in length and encoded a protein of 703 amino acid residues with a molecular mass of 80.5 kDa. Comparison of the rat liver and the human muscle sequences show that the amino- and carboxyl-terminal regions are quite divergent as compared to the internal sequences which show an 80% identity. The rat liver carboxyl-terminal region is truncated by 33 residues and has only 46% identity with the muscle sequence but retains the common feature of a low content of hydrophobic amino acids (13%). Phosphorylation sites 1a and 1b, which are the primary targets for phosphorylation by cAMP-dependent protein kinase, are absent in the liver sequence. The presence of these divergent, structurally anomalous carboxyl-terminal regions in liver and muscle glycogen synthase suggests the absence of the requirement that they possess a tertiary structure that is integral to that of the protein core. A model is proposed in which this region interacts with a catalytic core to maintain the I state, and in which phosphorylation serves to uncouple this interaction.

Amino Acid Sequence↗
PubMed1988

Regulation of glycogen synthesis in the liver.

The glycogen synthase-mediated reaction is rate-limiting for glycogen synthesis in the liver. Glycogen synthase has been purified essentially to homogeneity and has been shown to be a dimer composed of identical subunits. It is regulated by a phosphorylation-dephosphorylation mechanism, catalyzed by kinases and a phosphatase. The subunits of synthase D, the most phosphorylated form, each contain approximately 17 phosphates. The subunits of synthase I, the least phosphorylated form, each contain 14 phosphates. Thus, during the transition between these two forms, a net of three phosphoryl groups is added or removed. In synthase D, six of the phosphates are alkali-labile. In synthase I, three of the phosphates are alkali-labile. Therefore, all of the phosphorylation sites important in the interconversion of these two forms are alkali-labile (attached to serine or threonine residues). In short-term experiments using isolated hepatocytes, [32P]phosphate was only incorporated into the alkali-labile sites and the phosphate in these sites was shown to turn over rapidly. Glucose addition, which is known to reduce the proportion of synthase in the D form when assayed kinetically, also reduced the [32P]phosphate content. Glucagon addition, which increases the proportion of synthase in the D form, increased it. These changes do not appear to be site-specific. Ingestion or administration of fructose, or galactose, as well as glucose, result in a shift in synthase equilibrium in favor of the less phosphorylated forms. Possible mechanisms by which synthase phosphatase activity may be increased after ingestion of glucose or fructose, and thus shift the equilibrium in favor of the less phosphorylated forms, are discussed. The mechanism by which galactose may stimulate the phosphatase reaction is completely unknown.

Animals↗
PubMed1985

L-type glycogen synthase. Tissue distribution and electrophoretic mobility.

We previously reported (Kaslow, H.R., and Lesikar, D.D.FEBS Lett. (1984) 172, 294-298) the generation of antisera against rat skeletal muscle glycogen synthase. Using immunoblot analysis, the antisera recognized the enzyme in crude extracts from rat skeletal muscle, heart, fat, kidney, and brain, but not liver. These results suggested that there are at least two isozymes of glycogen synthase, and that most tissues contain a form similar or identical to the skeletal muscle type, referred to as "M-type" glycogen synthase. We have now used an antiserum specific for the enzyme from liver, termed "L-type" glycogen synthase, to study its distribution and electrophoretic mobility. Immunoblot analysis using this antiserum indicates that L-type glycogen synthase is found in liver, but not skeletal muscle, heart, fat, kidney, or brain. In sodium dodecyl sulfate-polyacrylamide gels of crude liver extracts prepared with protease inhibitors, rat L-type synthase was detected with electrophoretic mobility Mapp = 85,000. In contrast, the M-type enzyme in crude skeletal muscle extracts with protease inhibitors was detected with Mapp = 86,000 and 89,000. During purification of L-type synthase, apparent proteolysis can generate forms with increased electrophoretic mobility (Mapp = 75,000), still recognized by the antiserum. These M-type and L-type antisera did not recognize a protein with Mapp greater than phosphorylase. The anti-rat L-type antisera recognized glycogen synthase in blots of crude extracts of rabbit liver, but with Mapp = 88,000, a value 3,000 greater than that found for the rat liver enzyme. The anti-rat M-type antisera failed to recognize the enzyme in blots of crude extracts of rabbit muscle. Thus, in both muscle and liver, the corresponding rat and rabbit enzymes are structurally different. Because the differences described above persist after resolving these proteins by denaturing sodium dodecyl sulfate electrophoresis, these differences reside in the structure of the proteins themselves, not in some factor bound to the protein in crude extracts.

Animals↗
PubMed1985

In vivo phosphorylation of liver glycogen synthase. Isolation of the 32P-labeled enzyme and studies on the nature of the bound [32P]phosphates.

Our previous study (Tan, A. W. H., and Nuttall, F. Q. (1983) J. Biol. Chem. 258, 9624-9630) indicated that liver synthase D contained a large number of endogenous phosphates, 12 of which were stable and 6 labile to alkali treatment. We wished to investigate the nature of the phosphates on synthase which became isotopically labeled when inorganic [32P]phosphate was given either to intact rats or to isolated liver cells. An antibody against liver synthase D was used for the isolation of synthase. The antibody recognized both the phosphorylated and dephosphorylated form of the enzyme, native as well as partially cleaved species. A large enzyme form, with Mr of 90,000 as well as one with Mr of 73,000 was observed. A 61% decrease in [32P]phosphate was found in synthase when prelabeled liver cells were treated with glucose, whereas a 25% increase was seen in cells treated with glucagon. After [32P]synthase D was converted to synthase I by synthase phosphatase, 95% of the [32P]phosphate was lost. All of the bound [32P]phosphates were found to be labile to alkali. Thus, under the in vivo conditions used, the [32P]phosphates incorporated into synthase were characterized by their fast turnover rate, alkali lability and susceptibility to the action of synthase phosphatase, both in vivo and in vitro. These criteria serve to distinguish them from the slower turning-over, alkali-stable phosphates found previously in both synthases D and I.

Animals↗
PubMed1983

Endogenous phosphates on liver glycogen synthase D and synthase I. Studies on the number and location.

Synthase D and synthase I of high specific activity have been isolated from rabbit liver, with subunit Mr = 78,000 and 85,000, respectively. Minor bands of Mr = 78,000 and 71,000 were also observed, and these were shown to be proteolytic products containing synthase activity. Incubation with trypsin resulted in no activity changes, but there was a conversion of synthase I to the Mr = 78,000 species. Incubation with chymotrypsin produced no change in total synthase activity, but both enzymes were converted to the Mr = 71,000 species. Synthase I, after chymotrypsin treatment, became dependent on glucose-6-P for activity. Kinetic studies indicated that the chymotrypsin-treated synthase D and synthase I were not the same species. Synthase D contained 5.7 mol of alkali-labile phosphate/subunit and synthase I, 2.9 mol/subunit. With trypsin treatment there was little loss of phosphate from synthase. With chymotrypsin treatment, there was a loss of 3.1 and 1.5 mol of phosphate/subunit from synthase D and I, respectively. Some conversion to synthase I still occurred when chymotrypsin-treated synthase D was incubated with crude extract, suggesting that the phosphates which remained were still removable by synthase phosphatase. The presence of additional alkali-stable phosphates was indicated when the synthase samples were ashed. The total phosphates were 17.3 mol/subunit for synthase D and 13.4 mol/subunit for synthase I. Our results indicate that the liver synthase enzymes are highly phosphorylated and extremely susceptible to endogenous and exogenous proteolysis. The alkali-labile phosphates are distributed in chymotrypsin-sensitive as well as chymotrypsin-insensitive sites. Both sites are involved in the conversion of synthase D to synthase I.

Animals↗
PubMed1982

Liver phosphorylase kinase: characterization of two interconvertible forms and partial purification of phosphorylase kinase a.

The presence of two interconvertible forms of phosphorylase kinase has been confirmed in rat liver extracts. The pH optimum of the nonactivated form (PhK b) was lower than the pH optimum of the activated form (PhK a) as reported by others (2). In the absence of calcium the Km of PhK b for phosphorylase b was 53 +/- 10 U/ml with a Vm of 17 +/- 1 U/gm of tissue. The Km of PhK a for phosphorylase b was 20 +/- 2 U/ml with a Vm of 65 U/gm. Calcium stimulated both forms of phosphorylase kinase (A0.5 approximately 0.03 micro). In the presence of 0.1 microM calcium the Km for phosphorylase b of both forms of the enzyme was reduced. In addition, calcium increased the Vm of both forms, but the effect was greater for PhK b than for PhK a. The Km of both forms of phosphorylase kinase for ATP was 0.05 mM and was unaffected by calcium. All of these studies were done using liver phosphorylase b as substrate. Conditions for assaying PhK a activity virtually independent of PhK b activity also are indicated. This will enable the monitoring of interconversion reactions in tissue extracts. Phosphorylase kinase a was purified to near homogeneity using DEAE-cellulose, Sepharose 4B gel filtration and ATP affinity chromatography. The molecular weight was approximately 1 x 10(6). The pH profile, calcium requirements and kinetic constants were the same as those for PhK a in the crude extract.

Animals↗
PubMed1982

Glycogen synthase R in livers of starved rats and starved rats given glucose.

We reported that when synthase D was converted to synthase I in a rat liver extract, it progressed through a synthase form with activity characteristics which could not be explained by a mixture of synthase D and synthase I (Tan, A. W. H. (1981) Biochem. J. 200, 169-172). In this study we will borrow the "R" nomenclature to describe this "non-D" and "non-I" activity. Using activities measured at five different conditions and simultaneous equations, the amount of the three synthase forms in liver extracts can be estimated. During incubation of the liver extract, the amount of synthase R was found to increase with time and then to decrease as synthase I was generated, a profile typical of an enzyme intermediate. We investigated for the presence of synthase R in rat liver under different in vivo conditions. In contrast to the liver of fed rats which had very little synthase R, the liver of fasted rats was found to have 30% of its synthase in the R form. This synthase R was increased 2-fold when glucose was given and decreased to a very low level when glucagon was given. Synthase I was not detected, even in the livers of starved rats given glucose. Using conditions which were closer to those of the cell, synthase R was found to have relatively high activity, up to 70% that of synthase I. Based on these results, synthase R is proposed to be an active enzyme form responsible for glycogen synthesis in rat liver.

Animals↗
PubMed1981

Presence of an intermediate synthase form during the conversion of glycogen synthase D into synthase I in rat liver extract.

When synthase D was converted into synthase I in a liver extract, it progressed through a synthase form with activity characteristics that could not be explained by a mixture of the original synthase D and the final product, synthase I. This form was distinguished by an affinity for UDP-glucose, in the absence of glucose 6-phosphate, which was intermediate between those of the two known forms.

Animals↗
PubMed1981

Effect of starvation and insulin treatment on glycogen synthase D and synthase D phosphatase activity in rat heart.

We have previously shown that synthase phosphatase activity was decreased in starved animals and was rapidly restored by insulin administration (1). In order to determine whether the decreased phosphatase activity was due to a decrease in phosphatase enzyme per se or to a change in the substrate, synthase D, phosphatase activity has been determined using purified synthase D substrate. Using purified heart or liver synthase D, phosphatase activity was lower in extracts from starved animals than in fed animals. Insulin administration rapidly increased phosphatase activity in extracts from the starved animals. The total amount of endogenous synthase D which was convertible to synthase I was lower in extracts from starved animals, but this was rapidly increased within 15 minutes following insulin administration. These data suggest that starvation and insulin have a direct effect on the phosphatase enzyme activity per se and probably on the substrate suitability of synthase D as well.

Animals↗
PubMed1980

Characterization of the glycogen synthase D found in liver of the adrenalectomized fasted rats.

We have previously shown that the synthase D (UDPglucose:glycogen 4-alpha-D-glucosyltransferase, EC 1.4.1.11) present in the liver of the adrenalectomized fasted rat was not converted to synthase I by synthase phosphatase from normal animals, suggesting the presence of a non-substrate form of synthase D (Tan, A.W.H. and Nuttall, F.Q. (1976) Biochim. Biophys. Acta 445, 118--130). The enzymatic properties of this synthase D have now been examined. Using optimal assay conditions, the total amount of synthase D activity in the adrenalectomized fasted rats was similar to that of normal fed rats when 1% glycogen was included in the homogenizing buffer. However, the two enzymes appeared to have different affinities for the substrate, UDPglucose and the modifier, glucose-6-P. The changes in kinetic properties were not due to differences in glycogen or to a dialyzable modifier in the extracts. Synthase D from adrenalectomized fasted and from normal fed rats was partially purified. After DEAE-cellulose chromatography, modification appeared to have occurred such that the enzyme from the adrenalectomized fasted rat had properties similar to that of the normal fed rat. The enzymes were cold-labile, had different properties from enzymes in the crude extract and they were both converted to synthase I by synthase phosphatase. We conclude from these studies that the phosphorylation site in the synthase is in a flexible region of the protein. Changes in the ability of the synthase D to interact and be dephosphorylated by synthase phosphatase can occur readily in vivo and in vitro. The molecular basis for the modification remains unknown.

Adrenalectomy↗
PubMed1979

Growth hormone effects on creatine uptake by muscle in the hypophysectomized rat.

Specific radioactive enzyme assays were developed to measure the effect of growth hormone on kidney transamidinase and liver methyltransferase in the hypophysectomized rat. In contrast to minimal changes (20%) in liver methyltransferase, kidney transamidinase was decreased threefold in the hypophysectomized rat. Enzyme activities were equal to normal values in those rats receiving growth hormone for three days. The formation of creatine from radioactive precursors and the uptake of 14C-creatine in muscle was examined under these conditions. After injection of 14C-arginine in the hypophysectomized rat, the 14C-creatine content of muscle was greatly decreased compared to sham operated controls and the 14C-creatine content was normal after growth hormone administration. After injection of 14C-guanidoacetate and of 14-creatine, the 14C-creatine content of muscle was decreased in the hypophysectomized rat, but was equal to sham control values in rats receiving growth hormone. These studies indicate that the uptake of newly synthesized creatine by muscle is impaired in the hypophysectomized rat and that growth hormone can have a role in controlling the rate of creatine uptake by muscle in addition to its effect on kidney transamidinase and to other factors involved in creatine metabolism.

Amidinotransferases↗