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Biomedical subjects

C T Chang

Publications and source records attributed to C T Chang.

At least 91 records · Page 5Linked to original sources
PubMed1979

Enzyme affinity of the 5,6-dihydro derivatives of the substrate and product of thymidylate synthetase catalysis.

The 5,6-dihydro derivatives of 2'-deoxyuridine 5'-phosphate (2) and 2'-deoxythymidine 5'-phosphate (3) were synthesized and characterized. The affinities of 2 and 3 were compared to those of the substrate (2'-deoxyuridine 5'-phosphate) and product (2'-deoxythymidine 5'-phosphate) of the reaction catalyzed by thymidylate synthetase. In both cases, the enzyme affinity of the 5,6-dihydro derivatives was 50 times less than that of the substrate or product. The conclusions from this study are that a noncovalent complex of enzyme and a dihydro substrate or dihydro product is improbable in thymidylate synthetase catalysis and the covalent enzyme--substrate complex is more reasonable.

Chemical Phenomena↗
PubMed1979

5-[(4-Methyl-1,2,3,4-tetrahydroquinoxalyl)methyl]-2'-deoxyuridine 5'-phosphate: an analogue of a proposed intermediate in thymidylate synthetase catalysis.

In a study of the sequence steps involved in the mechanism of thymidylate synthetase catalysis, 5-[(N-methyl-piperazinyl)methyl]- (5) and 5-[(4-methyl-1,2,3,4-tetrahydroquinoxalyl)methyl]-2'-deoxyuridine 5'-phosphate (6) were synthesized. Compound 6 has high affinity for the Lactobacillus casei enzyme (Ki = 0.75 microM, KI/Km - 0.23), which is 50 times stronger than that of the piperazinyl derivative 5. Compound 6, a possible multisubstrate inhibitor, is an analogue of a proposed intermediate in the reaction mechanism wherein the enzyme is eliminated from the covalent complex (enzyme--substrate--cofactor) prior to the redox reaction leading to the products 2'-deoxythymidine 5'-phosphate and 7,8-dihydrofolic acid.

Deoxyuracil Nucleotides↗
PubMed1979

Abnormal neutrophil chemotaxis and random migration induced by aminoglycoside antibiotics.

Gentamicin and amikacin, administered in therapeutic doses to normal healthy adults, caused a transient decrease in chemotactic migration of their PMNs. In contrast, RM of leukocytes obtained from these individuals was increased significantly. The magnitude of these changes did not correlate with the serum antibiotic concentrations. Separate in vitro experiments with gentamicin, however, revealed an inverse dose-response relationship with chemotactic suppression. The mechanism(s) involved in modifications of these leukocyte functions is not well understood. These findings may be of clinical significance in patients, especially those with altered host defense mechanisms, who require therapy with these aminoglycoside antimicrobial agents.

Adult↗
PubMed1978

Circular dichroic analysis of protein conformation: inclusion of the beta-turns.

The mean residue ellipticity, [theta], at any wavelength, lambda, of a protein in aqueous solution is expressed as [theta]lambda = fH[theta]H infinity(1-k/n) + f beta[theta]beta + ft[theta]t + fR[theta]R with two constraints: 1 > or = fj > or = 0 and sigma fj = 1. The subscripts H, beta, t, and R refer to the helix, beta-form, beta-turn, and unordered form. The fractions, fj's, of 15 proteins are based on X-ray crystallography, ft refers to the net beta-turn after cancelling those residues having dihedral angles of opposite sign. The [theta]H infinity of an infinite helix and its chain-length dependence factor, k, were computed from the myoglobin data (Chen et al., 1974, Biochemistry 13, 3350). The average number of residues per helical segment, n, for 15 proteins was about 10, which can be used for proteins of unknown structure. The reference spectra of other three structural elements are computed by a least-squares method. Once the reference spectra are chosen, the same equation above can be used to estimate the fractions of the secondary structure of a protein from its CD data points between 190 and 240 nm at 1-nm intervals. The computed helical content is usually good to excellent (concanavalin A is a notable exception). Inclusion of the beta-turn in the analysis improves the correlation for the estimates of the beta-form, but the computed beta t values are not significantly correlated with the X-ray results. Matrix formulation proves the equivalence of the least-squares method and the integral curve-fitting.

Animals↗
PubMed1978

Pharmacokinetics and safety of cefamandole in infants and children.

Cefamandole, a new cephalosporin antibiotic, has greater activity against common pathogens, including Escherichia coli, Haemophilus influenzae, and Proteus (including indole-positive strains), than available cephalosporin drugs. We have evaluated the safety and pharmacokinetics of this drug in 30 infants and children. Blood levels and urinary excretion of the drug were similar to those previously found in adults. The only side effects were mild and transient elevation of serum glutamic oxalacetic transaminase in 12 patients and of blood urea nitrogen in 1 patient in whom serum creatinine remained normal and unchanged.

Adolescent↗
PubMed1977

Bacterial colonization of infants raised in incubators and under radiant heaters.

To assess the effect of open radiant heaters on bacterial colonization of neonates, 24 infants were raised under radiant heaters and 34 in standard incubators. Cultures of the nose, groin, and umbilicus were taken daily for the first 3 days of life. For infants raised in incubators, colonization rates with Staph. aureus ranged up to 47%. Among infants raised under radiant heaters (8 of whom had topical antibiotics applied to the umbilicus), only one was colonized with this organism. Even if the 8 treated infants were excluded, the prevalence of Staph. aureus was significantly greater at the umbilicus and groin in infants raised in incubators.

Bacteria↗
PubMed1976

Amikacin pharmacokinetics in the therapy of childhood urinary tract infection.

Amikacin, a new aminoglycoside antibiotic with a spectrum similar to that of gentamicin, has been used mainly in adults. This report summarizes the first use of this drug in children with urinary tract infection. Organisms were eradicated in all cases and recurrent infection occurred in one half after one week. No evidence of ototoxicity or nephrotoxicity was found. Four children developed transient elevation of serum glutamic oxaloacetic transaminase. Serum level (17 mug/ml) of the drug at one hour and its urinary excretion in six hours (60% of the dose) was comparable to those of adults. This antibiotic is potentially valuable and has thus far not shown major toxicity when given for up to 11 days in patients with normal renal and liver functions.

Amikacin↗