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Biomedical subjects

C T Peng

Publications and source records attributed to C T Peng.

At least 37 records · Page 2Linked to original sources

Molecular characterization of secretor type alpha(1, 2)-fucosyltransferase gene deficiency in the Philippine population.

We analyzed the seven mutations which are responsible for the deficiency of the secretor type alpha(1,2)-fucosyltransferase gene product, Se enzyme, in the Philippine population. One hundred and one unrelated Filipinos in Taiwan were studied. A new mutation, a 3-base pair deletion from nt 688 through 690, was found in two (0. 1%) of 202 chromosomes. The frequencies of six other mutated alleles were as follows: 71/202 (35.2%) were cDNA 385 A-->T missensed mutation (se2), 28/202 (13.9%) were C571T nonsense mutation (se3), 16/202 (7.9%) were G849A nonsense mutation (se4), 4/202 (1.9%) were G428A nonsense mutation (se1), and 81/202 (40.1%) were wild-type allele (Se). No C628T nonsense mutations (se5) or fusion genes of pseudogene and FUT2 gene (se 6) were found in this population. For the molecular basis of phenotype Le(a+ b-): eight cases had se2/se2, six cases had se2/se3, two cases had se3/se4, one case was homozygous of se4, one case was se3/se1, and two cases were se2/se7. For the Le(a+ b+) phenotype: four cases had se2/se2, two cases had se2/se3, one case was se3/se3, and one case was se2/se4. For the Le(a- b+) phenotype: 16 cases were Se/Se, 21 cases were Se/se2, six cases were Se/se3, five cases were Se/se4, and two cases had Se/se1. Our results suggest that the genotypes of the alpha(1, 2)-fucosyltransferase gene in phenotypes Le(a+ b+) and Le(a+ b-) are the same. Other factors that play important roles may cause the differences between these two phenotypes. Several hotspot mutations in the alpha(1,2)-fucosyltransferase gene are responsible for the nonsecretor phenotype.

Fucosyltransferases↗

Molecular analysis of secretor type alpha(1,2)-fucosyltransferase gene mutations in the Chinese and Thai populations.

BACKGROUND: The human Lewis histo-blood group system belongs to a family of structurally related oligosaccharides. The mutations of fucosyltransferase genes alpha(1,2)-fucosyltransferase (FUT2 or Se) and alpha(1,3/1,4)-fucosyltransferase (FUT3 or Le), are responsible for the polymorphism of Lewis blood group phenotypes. However, a population study of the FUT2 mutation in Chinese and Thais has not yet been done, and there is some controversy about the phenotypes of Le(a+b+) and Le(a+b-). STUDY DESIGN AND METHODS: One hundred twentyfour Chinese and 70 Thais were phenotyped for Lea and Le(b). DNA samples were studied by polymerase chain reaction and then by a restriction enzyme digestion method to distinguish wild-type and six known mutations. Direct sequencing was done for controls and some uncertain cases. RESULTS: A new mutation, C302T mutation, was found in 2 of 136 chromosomes in the Thai population; none were discovered in Chinese. The frequencies of the normal and six mutant alleles among Chinese and Thais, respectively, were as follows: 134 (54.0%) of 248 and 58 (41.4%) of 140 were wild-type (Se); 0 of 248 and 2 of 140 (both 1.4%) had the G428A mutation; 120 (48.4%) of 248 and 75 (53.6%) of 140 had the A385T mutation; 2 (0.81%) of 248 and 0 of 140 had the C571T mutation; and 1 (0.4%) of 248 and 3 (2.2%) of 140 had the G849A mutation. Only 1 Chinese (0.4%) of 248 had the C628T mutation, and none had fusion gene mutation. CONCLUSION: The FUT2 genes encoding for the phenotypes Le(a+b+) and Le(a+b-) are the same. The function and character of the mutant enzyme may play an important role in the phenotype. The methods used in this study are clinically applicable in population studies of the FUT2 gene polymorphism to explore relationships among different ethnic groups and correlations between phenotype and genotype.

China↗

Different race, different face: minor anomalies in Chinese newborn infants.

OBJECTIVE: To define the nature and incidence of minor anomalies in Chinese newborn infants and to evaluate the validity of the hypothesis that infants with three or more minor surface anomalies will also have a major malformation. METHODS: A total of 3,345 Chinese newborn infants were examined based on a list of 67 items of minor anomalies. RESULTS: About 44.9% of the newborn infants had at least one minor anomaly that was unrelated to gender, maternal age, or gestational age, but significantly associated with fetal presentation. Breech-presented newborn infants had double the risk of minor anomalies. Simian crease, upward slant and frontal bossing could be considered normal variants for Chinese newborn infants, because the incidence of each was higher than 4%. CONCLUSIONS: Although some studies have shown that approximately 90% of infants having three or more minor anomalies are associated with a major malformation, we found only a 10.1% predictive value based on this study. Nevertheless, we suggest that infants with three or more minor anomalies be carefully evaluated for the possibility of major malformation in order to provide early management.

Abnormalities, Multiple↗

Echocardiographic flow pattern of patent ductus arteriosus: a guide to indomethacin treatment in premature infants.

AIM: To compare the efficacy and safety of an indomethacin treatment strategy based on serial echocardiographic measurement of patent ductus arteriosus (PDA) flow pattern with a standard protocol. METHODS: Neonates weighing less than 1500 g at birth, who required respiratory support, and who had developed symptomatic PDA, were studied. PDA was confirmed in all infants using colour Doppler echocardiography, and serial observations of the ductal flow pattern were made. Infants randomly assigned to receive conventional indomethacin treatment (protocol group) were given an initial dose of 0.2 mg/kg, followed by 0.1 or 0.2 mg/kg, depending on age, 12 hourly for two further doses, and were eligible for a second course. Those randomly assigned to the ductal flow pattern assessment (ECHO group) received further doses of indomethacin after 24 hours, only if their flow pattern was "pulsatile" or "growing." RESULTS: There was no significant difference in the primary outcome measures between the two groups. The closure rate was 89.1% and 87.2%, respectively, in the protocol and ECHO groups. The mean (SD) doses of indomethacin were significantly higher in the protocol group: 3.2 (1.4) doses compared with 1.6 (0.9) doses. There was a significantly higher incidence of hypoglycaemia, impaired urine output, and gastrointestinal bleeding in the protocol group. CONCLUSIONS: An indomethacin treatment strategy for PDA based on measurement of the ductal flow pattern is associated with a reduction in the total doses of indomethacin administered, and a reduced rate of complications, compared with a conventional protocol. There is no difference in closure rate.

Anti-Inflammatory Agents, Non-Steroidal↗

Early dexamethasone therapy and blood cell count in preterm infants.

OBJECTIVE: To assess the effects of early postnatal dexamethasone therapy on hematologic values in preterm infants. MATERIALS AND METHODS: We reviewed the hematologic data of 179 preterm infants who participated in a double-blind clinical trial of early postnatal dexamethasone therapy (<12 hours after birth) for the prevention of chronic lung disease. One group (86 infants) received saline and the other group (93 infants) received dexamethasone. Dexamethasone was given intravenously every 12 hours in tapering doses: 0.25 mg/kg on days 1 to 7, 0.12 mg/kg on days 8 to 14, 0.05 mg/kg on days 15 to 21, and 0.02 mg/kg on days 21 to 28. Blood samples were obtained on days 0, 3, 7, 10, 14, 21, and 28. None of the infants received prenatal steroid therapy. RESULTS: Multiple regression analysis revealed significant differences in the values versus time curves of the white blood cell, neutrophil, lymphocyte, basophil, and eosinophil counts between the two groups. The white blood cell count was significantly higher in the dexamethasone group on days 7 through 14, and this was associated with significantly higher numbers of segmented neutrophils and band forms and significantly lower numbers of lymphocytes and eosinophils. The hematocrit and platelet counts were similar in the two groups throughout most of the trial. Except for platelet count, steroid therapy did not alter the hematologic values for infants with bacteremia. CONCLUSION: Dexamethasone affects white blood cell, segmented neutrophil, lymphocyte, basophil, and eosinophil counts in neonates. This should be taken into consideration when evaluating preterm infants who are receiving dexamethasone.early dexamethasone therapy; neonatal blood count; preterm infant; respiratory distress syndrome.

Bacteremia↗

Molecular diagnosis of patients with beta-thalassemia major in central Taiwan by amplified created restriction site analysis.

beta-Thalassemia, a hematologic disorder characterized by the deficiency or the absence of beta-globin production, is the most widespread inherited disorder in the world; it is also common in Taiwan. We studied 38 patients in central Taiwan with beta-thalassemia major, using amplified created restriction site analysis for detection. On analysis, six different point mutations were found among 76 chromosomes, of which 32 chromosomes (42.1%) had a C to T substitution at nucleotide 654, 30 (40%) had frameshift codons 41/42 with four nucleotides (TCTT) deletion, 7 (9.2%) had an A to T substitution at codon 17, 3 (3.9%) had frameshift codons 71/72 (insertion of A), 2 (2.6%) had an A to G substitution at position -28, and 2 (2.6%) had frame-shift codons 27/28 (insertion of C). The first two mutations accounted for 62 of the 76 beta-thalassemia mutations in this study. As to mutations in each individual with beta-thalassemia major, the incidence of compound heterozygotes of two different mutations was higher than that of homozygotes of a single mutation (60% vs 40%). Compound heterozygotes of C to T substitution at nucleotide 654 of IVS-2 and frameshift codons 41/42 with four-nucleotide deletion was the most common pattern of beta-thalassemia mutations in each individual (23.7%). Our results were unique compared with those from similar studies performed in southern China. Frequencies of beta-thalassemia mutations found in the current study were assessed and compared with frequencies found in previous studies conducted in northern and southern Taiwan.

Adolescent↗

Prolonged severe withdrawal symptoms after acute-on-chronic baclofen overdose.

INTRODUCTION: Baclofen is frequently used to treat muscle spasticity due to spinal cord injury and multiple sclerosis. Baclofen overdose can lead to coma, respiratory depression, hyporeflexia, and flaccidity. An abrupt decrease in the dose of baclofen due to surgery or a rapid tapering program may result in severe baclofen withdrawal syndrome manifesting hallucinations, delirium, seizures, and high fever. Severe baclofen withdrawal syndrome secondary to intentional overdose, however, has not received mention. CASE REPORT: A 42-year-old male receiving chronic baclofen therapy, 20 mg/d, attempted suicide by ingesting at least 800 mg of baclofen. He was found in coma 2 hours postingestion with depressed respirations, areflexia, hypotonia, bradycardia, and hypotension. Treatment with intravenous fluids, atropine, dopamine, and hemodialysis was associated with restoration of consciousness within 2 days but disorientation, hallucinations, fever, delirium, hypotension, bradycardia, and coma developed during the following week. Baclofen withdrawal syndrome was not diagnosed until hospital day 9, when reinstitution of baclofen rapidly stabilized his condition. Oral overdosage of baclofen causes severe neurological and cardiovascular manifestations due to its GABA and dominant cholinergic effects. Severe baclofen withdrawal syndrome is manifest by neuropsychiatric manifestations and hemodynamic instability. Caution should be exercised after a baclofen overdose in patients receiving chronic baclofen therapy.

Adult↗

Retrieval of structure information from retention index.

The chromatographic identity of a compound can be determined by four parameters, namely, I, A, Z and (GRF). These are interrelated in a linear regression equation, given in the paper as Eq. 8. The retrieval of structural information from retention data requires the introduction of a new meaning to the Kováts retention index, the use of column difference (delta I) to characterize functional groups, the redefinition of the role of electronegative oxygen and nitrogen atoms, and the division of retention index (I) into contributions from atoms and from functional groups. The separation of retention index (I) into molecular and interaction contributions is a necessary condition for retention index prediction from structure and also for structure information retrieval from retention data. According to Eq. 8 the retention index is uniquely determined by three parameters, namely A, Z and (GRF). For prediction of retention index, the A value is assigned a value of 100 index units (i.u.), the Z value is obtained directly from the compound, and the (GRF) value is pre-calibrated. In Eq. 10, the m and n values represent the pre-calibrated terms for a quantitative structure-retention index relationship. These terms account for the positive and negative retention contributions from polar and polarizable atom groups. All atom groups that are different from methylene and methyl groups will interact with the stationary phase and contribute to retention. The m and n values for various functional, polar and polarizable atom groups and their column differences (delta I values) are the results of interactions between the solute and the stationary phase and are structure dependent. The interaction increases with increasing polarities of the solute and the stationary phase. The column difference not only reflects the strength of the interaction, but is also characteristic of the functional and polarizable groups. The retrieval of structural information from retention data is equivalent to obtaining Z and (GRF) values from known I and delta I values, which is straightforward for monofunctional compounds. For multi-functional compounds, additional data will be needed for retrieval of structural information. These can be obtained from derivatization of the unknown compound, from its chemical reactions with other reagents, from GC-MS analysis and from structure match using internal or external standards. The additional data required will depend upon the complexity of the unknown structure. This approach demonstrates that a system can be devised to utilize GC retention characteristics uniquely for structure elucidation.

Chemistry, Physical↗

Successful treatment with cyclosporin A in a child with acquired pure amegakaryocytic thrombocytopenic purpura.

Idiopathic acquired pure amegakaryocytic thrombocytopenic purpura (APATP) in young patients (non-neonates) is a rare disorder with a variable clinical course. Cure is unusual. A 13.5-year-old boy with idiopathic APATP was treated with cyclosporin A. Apparently effective, the treatment resulted in the reappearance of marrow megakaryocytes and normalization of platelet count.

Adolescent↗

Prediction of retention indexes. IV. Chain branching in alkylbenzene isomers with C10-13 alkyl chains identified in a scintillator solvent.

Twenty solvent components in a commercial scintillator were identified by chromatography on polar and non-polar columns and by gas chromatography-mass spectrometry (GC-MS) as isomeric 1-(alkyl)m(alkyl)nbenzenes with formulae C16H26, C17H28, C18H30 and C19H32. These isomers occur in four clusters of chromatographic peaks representing ca. 6, 44, 34 and 16% of the total solvent mass. The retention indexes of the isomers are influenced by the lengths of the alkyl chains in the molecule, and their polarity and polarizability can affect the column difference, which is the difference between retention indexes on polar and non-polar columns. 1-Methylalkylbenzenes have higher retention indexes and larger column differences than the evenly distributed isomers, such as 1-butylhexyl-1-pentylhexyl, 1-pentylheptyl- and 1-pentyloctylbenzene. The results demonstrate the effect of structural symmetry on the retention indexes of the isomers. This study shows that the ability to relate GC data and column differences to structures can facilitate the interpretation of GC-MS data in the structure identification of isomers.

Alkylation↗

Noma neonatorum: an unusual case of noma involving a full-term neonate.

Noma neonatorum is a gangrenous process that occurs in the oral, nasal or anal area and occasionally the eyelids and scrotum of the newborn. The disease is caused by Pseudomonas aeruginosa and usually affects premature ill babies during the first few weeks of life. A full-term neonate with nasal and scrotal noma is uncommon and is therefore reported.

Humans↗

Prediction of retention indexes. II. Structure-retention index relationship on polar columns.

A method is described for the prediction of the retention index (I) from chemical structure, using the number of atoms in the molecule (Z), the I increment for atom addition (A) and the group retention factors (GRFs) of the functional groups and substituents. This method can predict the retention indexes of a wide range of compounds, such as acids, alcohols, amines, acid esters, aldehydes, ketones, ethers, aromatic hydrocarbons, alicyclics, heterocyclics, etc. on polar as well as non-polar columns to within 3% error. Accurate A and GRF values are essential to the prediction. These values can be obtained from homologous series, but a system of arbitrarily assigned A value and adjusted GRFs are also used. The GRFs of the substituents and functional groups depend on the polarity and polarizability of the analyte and the stationary phase and also on the molecular connectivity of the atoms, namely, primary, secondary and tertiary carbon atoms or hydrogen atoms, to which these groups are attached. Highly polar and polarizable groups can alter the A value. When the functionality of a group is masked by substitution, the analyte molecule will tend to behave chromatographically like hydrocarbons. The difficulty in predicting the I values of compounds of multi-functionality by the rule of additivity is the unknown intramolecular interaction that can alter both A and GRF values.

Alcohols↗

Prediction of retention indexes. III. Silylated derivatives of polar compounds.

Polar compounds containing hydroxyl, amino and carboxyl groups, singly or in combination, can be chromatographed after the polar functional groups are silylated. The silylated derivatives of acids, alcohols, amines, diols, amino alcohols, amino acids are shown to behave chromatographically as hydrocarbons, and their retention indexes can be readily predicted from their base values. The column difference, namely, the difference between the retention indexes of the analyte on polar and non-polar columns is minimal for the silylated derivatives in comparison to that observed for the underivatized analytes. This minimal column difference is attributed to the hydrocarbon-like chromatographic characteristics of the silylated derivatives. The retention indexes of the silyl derivatives appear to correlate with the atom number Z of the analyte.

Acids↗

Mechanism-based inactivation of bovine adrenal cytochromes P450 C-21 and P450 17 alpha by 17 beta-substituted steroids.

A series of progesterone derivatives has been studied as potential inactivators of the bovine adrenocortical cytochromes P450, P450 17 alpha, and P450 C-21. Replacement of the 21-methyl group of progesterone with a difluoromethyl group resulted in a selective inactivator of P450 C-21 in a reconstituted system. The loss of 21-hydroxylase activity caused by this compound exhibits a number of characteristics of mechanism-based inactivation including NADPH dependence, pseudo-first-order kinetics, saturability, irreversibility, and protection by substrate. In addition to the difluoro compound, 21,21-dichloroprogesterone, the acetylenic compound pregn-4-en-20-yn-3-one, and the olefinic compound pregna-4,20-dien-3-one all inactivate P450 C-21. In contrast, the only compound to inactivate the rabbit adrenal progesterone 21-hydroxylase is 21,21-dichloroprogesterone. In binding studies, the 21,21-dihalo steroids produce a greater maximal type I spectral shift of P450 C-21 than the two 17 beta-unsaturated steroids. The dihalo compounds inactivate P450 C-21 by both heme destruction and protein modification as shown by significant decreases in residual 21-hydroxylase activity and spectrally detectable P450 after incubation with P450 C-21 in a reconstituted system. Liquid chromatographic and mass spectral analyses of the organic extracts from these incubations showed that 21-pregnenoic acid is a major metabolite of the dihalo compounds with a partition ratio of 5 nmol of acid produced/nmol of P450 C-21 inactivated. This supports the hypothesis that inactivation proceeds in part through an acyl halide intermediate. In contrast, the acetylenic compound pregn-4-en-20-yn-3-one inactivates P450 C-21 mainly by protein modification, producing an NADPH-dependent irreversible type I spectral shift. The stoichiometry of inactivation is approximately 1.5 nmol of compound bound/nmol of enzyme inactivated, indicating selective modification of the enzyme at or near the substrate binding site.

Adrenal Glands↗

Prediction of retention indexes. I. Structure-retention index relationship on apolar columns.

A simple method is reported for predicting the retention index (RI) of a chemical compound from the number of carbon and carbon equivalent atoms in the molecule, the RI increment for atom addition and the group retention factors (GRFs) for substituents and functional groups. Atoms other than carbon such as oxygen, nitrogen, sulfur, chlorine, bromine and iodine are assigned carbon atom equivalency of approximately 1, 1, 2, 2, 3 and 4, respectively and are counted for their contribution towards RI prediction. The GRFs of substituents and functional groups are derived from the RIs of reference compounds and series of homologues. Ring structures, ring fusion, ring connection, iso- and neo-carbons, chain branching and unsaturation are also assigned GRFs. The predicted RIs of a number of alicyclic, aliphatic and aromatic hydrocarbons, primary, secondary and tertiary alcohols, phenols, aliphatic amines, aromatic amines, heterocyclics, carboxylic acids, acid esters, aldehydes, ketones, and halogenated compounds, are found to be within +/- 3% of the observed values. The structure-retention index relationship thus developed is extremely useful in the tentative identification of radioactive side products formed in tritium labeling by radiation-induced methods.

Alcohols↗

Metabolic fate in the dog of the nitroxide moiety in a compound with potential utility as a contrast agent in MRI.

Nitroxides, paramagnetic compounds with demonstrated effectiveness as contrast agents in proton magnetic resonance imaging, shorten the relaxation times of protons and therefore cause an increase in image intensity in tissues into which they distribute. In this study, the metabolic fate of the nitroxide moiety was examined in the dog using a pyrrolidine nitroxide derivative, 2,2,5,5-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid, for which contrast-enhancing properties have been previously studied in animals. After radiolabeling by microwave discharge in the presence of tritium gas, the compound was administered intravenously to a dog. Ninety-four percent of the radioactivity injected was recovered in urine within 3 days; the majority (90%) was excreted during the first 6 h. The radioactivity in the urine was identified as either the unchanged nitroxide or its corresponding hydroxylamine. Neither complete reduction of the nitroxide moiety to the amine nor any other metabolic transformation was observed.

Animals↗