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Biomedical subjects

J C Chang

Publications and source records attributed to J C Chang.

At least 235 records · Page 13Linked to original sources
PubMed1979

Suppression of the nonsense mutation in homozygous beta 0 thalassaemia.

The common form of beta thalassaemia associated with elevated haemoglobin A2 levels can be broadly classified as beta + or beta 0 type according to the presence or absence of beta-globin chain synthesis in the homozygous state. The molecular pathology of each type is heterogeneous. Apart from a subgroup of Indo-Pakistani patients, the beta-globin structural gene is intact in the majority of patients with beta 0 thalassaemia. The amount of beta-globin mRNA present in the reticulocytes of these patients varies: in some it is absent or barely detectable; in others, a substantial amount is present, but it is nonfunctional. We recently demonstrated that the molecular lesion in a Chinese patient with nonfunctional beta-globin mRNA was due to the mutation of the normal lysine codon AAG at amino acid 17 to the amber terminator codon UAG, which prematurely terminates the beta-globin chain. In the present study we demonstrate the first example of a nonsense mutation in humans which can be suppressed in vitro by the suppressor tRNA, as has been found in other eukaryotic cells and viruses.

Codon↗
PubMed1979

Origin of observed changes in 14N hyperfine interaction accompanying R leads to T transition in nitrosylhemoglobin.

Theoretical investigations of electronic distributions in eight different structural forms of nitrosylhemoglobin were carried out to study the changes in (14)N hyperfine interaction observed with the transition from R to T structures under the influence of inositol hexaphosphate or changing pH. Four of the eight forms studied consisted of protonated and deprotonated N(pros) in the proximal imidazole ligand with linear and bent Fe-N-O structures. Two other forms had a straight Fe-N-O structure and Fe-Im bond stretched by 0.5 and 1.0 A. The other two systems we have studied are five-liganded NO-heme with bent and straight Fe-N-O structures. Our investigations show that arrangements of energy levels did not differ significantly among all the structures, the unpaired electron always occupying an antibonding orbital with d(z)2 symmetry. The protonated and deprotonated systems with either linear or bent Fe-N-O structure showed substantial hyperfine interaction of the (14)N nuclei of the NO group and the N(epsilon) atom of the proximal imidazole, indicating that a 9-line electron spin resonance hyperfine pattern (R structure) would be expected in all four cases. On the other hand, the extensions of the Fe-Im bond produce a sizeable decrease in the (14)N(epsilon) hyperfine interaction, indicating that an extension beyond 1.0 A would provide a 3-line hyperfine pattern close to that found for the five-liganded NO-heme system. Our results thus provide quantitative support for the model of severe extension or cleavage of the Fe-N(epsilon) bond proposed in the literature for explaining the R-to-T transition of the alpha-chain of nitrosylhemoglobin.

Electron Spin Resonance Spectroscopy↗
PubMed1979

beta 0 thalassemia, a nonsense mutation in man.

We determined the complete nucleotide sequence of the 5' noncoding region and the first 74 amino acids of the nonfunctional beta-globin mRNA in a patient with homozygous beta 0 thalassemia. We identified the molecular defect as a single nucleotide substitution in the coding region of the mRNA. At the position corresponding to amino acid 17, replacement of an adenine by a uracil changes the triplet AAG, which codes for lysine in the normal beta chain, to an amber termination codon, UAG. This type of beta 0 thalassemia represents an example of a nonsense mutation in man.

Base Sequence↗
PubMed1978

Theory of proton hyperfine interactions in bacterial photosynthetic systems. Bacteriopheophytin cation and anion.

The electronic structures of the cation and anion of bacteriopheophytin alpha monomer are investigated by the self-consistent charge extended Hückel procedure including both pi and sigma electrons in the molecule. The calculated electron distributions are tested by comparison of the predicted hyperfine fields at proton sites with experimental data in both the ions and most important, by their ability to explain the observed trend in the hyperfine fields in going from the cation bacteriopheophytin+ alpha to the anion, a trend that is similar in many respects to the corresponding observed trend for the bacteriochlorophyll alpha cation and anion. Good agreement is obtained with experiment both for the absolute values of the observed proton hyperfine fields in both bacteriopheophytin a cation and anion as well as the ratio of the corresponding fields for the two systems. In particular, our calculated electron distributions in the two molecules lead, for the cation, to substantially different proton hyperfine fields for the two methyl groups attached to rings I and III, while for the anion, the corresponding fields are much closer to each other, a trend in good agreement with recent data. Also explained are the features of larger methine hyperfine constants in the anion as compared to the cation and the reverse trend for the protons in rings II and IV. Other features of the calculated electron distributions in the cation and anion are discussed and compared with each other. Possible additional measurements in the two systems that could provide further tests of the theoretically obtained electron distribution will be pointed out.

Bacteriochlorophylls↗
PubMed1978

The nucleotide sequence of the 5' untranslated region of human gamma-globin mRNA.

The nucleotide sequence of the entire 5' untranslated region of human gamma-globin mRNA has been determined. This was accomplished by analyzing complementary DNA (cRNA) synthesized from the mRNA with reverse transcriptase. The CDNA was labeled at its 3' end with 32"p using terminal deoxynucleotidyl transferase, digested with the restriction endonuclease Hae III and the end-labeled fragment isolated ans sequenced by the method of Maxam and Gilbert. Including the initiation codon AUG, the 5' untranslated region of human gamma-globin mRNA contains 57 nucleotides, compared to 41 in alpha- and 54 in beta-globin mRNA. There is very little homology between alpha and gamma sequences in the 5' region. There is considerable homology between beta- and gamma-globin mRNAs in the regions proximal and distal to the initiation codon, but the entire sequence shows less homology than the human and rabbit beta-globin mRNAs. The hexanucleotide sequence CUUCUG is found near the 5' ends of all three human globin mRNAs, suggesting a possible role of this sequence or ribosomal binding. Both guanosine and cytidine were found at the 19th nucleotide position from the 5' end of the gamma mRNA. We believe this heterogeneity arises from the difference in nucleotide sequence between the A gamma and G gamma loci.

Base Sequence↗
PubMed1977

Critical appraisal of electronic structure of metmyoglobin. 14N and 57Fe hyperfine interactions.

The electronic structure of metmyoglobin is subjected to a critical examination by comparison of results of recent ENDOR measurements of nitrogen hyperfine interaction constants on the porphyrin ring and on the proximal histidine linking the heme to the protein with theoretical values for these properties from calculated electronic wavefunctions for this molecule. The observed interesting trends of the 14N hyperfine data as well as available 57Fe data are both successfully explained showing that theory has provided a satisfactory description of the electronic distribution in this important molecule.

Ferric Compounds↗
PubMed1977

The nucleotide sequences of the untranslated 5' regions of human alpha- and beta-globin mRNAs.

The complete sequences of the untranslated 5' regions of human alpha- and beta-globin mRNAs were determined by sequence analysis of full-length cDNAs. The single-stranded cDNAs were digested with the restriction endonuclease Hae III, and the two 3'-terminal fragments of 75 and 132 nucleotides, complementary to the 5' termini of the alpha- and beta-globin mRNAs, respectively, were isolated and sequenced. Including the initiation codon AUG, the untranslated 5' regions of human alpha- and beta-globin mRNAs contain 41 and 54 nucleotides, respectively, and exhibit striking homologies with the corresponding sequences in the rabbit. Human alpha- and beta-globin mRNAs have five bases in the region of the initiation codon that may form base pairs with the 3' terminus of 18S rRNA. Stable secondary structures with hairpin loops can be constructed in the untranslated 5' regions.

Base Sequence↗
PubMed1977

Authentic beta-globin mRNA sequences in homozygous betaO-thalassemia.

In a patient with homozygous betaO-thalassemia in whom studies of reticulocyte hemoglobin synthesis showed no beta-globin chain synthesis in vivo and in vitro, molecular hybridization studies revealed RNA sequences complementary to beta-globin cDNA. The fact that these sequences were authentic beta-globin mRNA was shown by fingerprint analysis of T1 ribonuclease-digested mRNA and by sequencing of oligonucleotides unique to beta-globin mRNA. The beta-mRNA that failed to direct beta-globin chain synthesis was not detectably shortened or degraded and contained poly(A) sequences.

Adult↗