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Biomedical subjects

A Wang

Publications and source records attributed to A Wang.

At least 325 records · Page 18Linked to original sources

Serial delayed cutaneous hypersensitivity skin testing with multiple recall antigens in healthy volunteers: booster effect study.

Booster effects on delayed cutaneous hypersensitivity (DCH) responses have been demonstrated for various antigens when DCH is measured by the Mantoux technique. In the present study, we investigated this possibility when assessing DCH responses using the Multitest CMI multipuncture technique with simultaneous injections of seven test antigens and a control. The DCH responses were quantified for each antigen and for the overall DCH response expressed as a DCH score. In a group of healthy volunteers, DCH was repeatedly tested either 1 month apart or 2 months apart at least six times. When volunteers remained healthy, DCH variations were observed with only two of seven tested antigens: streptococcus which slowly decreased (P = .012) and proteus which slowly increased (P = .04). Responses to the other antigens and the DCH score remained stable. In contrast, greater DCH variations were observed when infections occurred. The results with the Multitest CMI multipuncture show that repeated application had minimal booster effect on DCH responses and may be used to evaluate and follow immunocompetence of patients.

Arm↗

Site-specific mutagenesis of the human interleukin-2 gene: structure-function analysis of the cysteine residues.

The gene encoding human interleukin-2 (IL-2) has been cloned from human spleen cells, peripheral blood lymphocytes, and the Jurkat cell line. Nucleotide sequence analysis of the gene revealed that the encoded IL-2 protein has three cysteines located at amino acid residues 58, 105, and 125 of the mature protein. Site-specific mutagenesis procedures were used to modify the IL-2 gene by changing each of the cysteine codons individually to serine codons. Substitution of serine for cysteine residues at either position 58 or 105 of the IL-2 protein substantially reduced biological activity, indicating that the cysteines at these positions are necessary for maintenance of the biologically active conformation and may therefore be linked by a disulfide bridge. The modified IL-2 protein containing a substitution at position 125 retained full biological activity, suggesting that the cysteine at this position is not involved in a disulfide bond and that a free sulfhydryl group at that position is not necessary for receptor binding.

Amino Acid Sequence↗

Osteosarcoma: intra-arterial treatment of the primary tumor with cis-diammine-dichloroplatinum II (CDP). Angiographic, pathologic, and pharmacologic studies.

Intra-arterial CDP was utilized to treat the primary tumor in 11 pediatric patients with osteosarcoma and in one with malignant fibrous histiocytoma. The investigation commenced with a phase I-II pilot study in four osteosarcoma patients. A dose of 150 mg/m2 was found to be safe and effective in producing a clinical response. This was followed by a definitive study in the remaining seven osteosarcoma patients and in the one malignant fibrous histiocytoma patient. The results were assessed by specific clinical, pharmacologic, radiographic and pathologic criteria. The overall response in the definitive study was 50% with two patients exhibiting total tumor destruction. The success of intra-arterial CDP was attributed to its ability to achieve high local drug concentration and tumor penetration. This was demonstrated by pharmacologic studies.

Adolescent↗

Transductional instability of Tn5-induced mutations: generalized and specialized transduction of Tn5 by bacteriophage P1.

Generalized transduction is commonly used to move transposon-induced mutations among bacterial strains by selecting for inheritance of a transposon-encoded resistance determinant. Although complete cotransduction of the resistance determinant and the chromosomal mutation might be expected, it is often found that when Tn5(Kan) insertion mutations are transduced by bacteriophage P1 most of the nonmutant kanamycin-resistant transductants area due to specialized transduction of Tn5. Such P1::Tn5 specialized transducing phage are not found when a mutant Tn5 element lacking a functional transposase is employed.

Coliphages↗

[Retrospective study of 290 cases of hyperthyroidism after 55 years of age without previously documented thyroid disorders].

Previous studies having shown differences in the clinical presentation of hyperthyroidism in the young and in the over sixty-years old patients, we studied the presentation of hyperthyroidism of late onset without previous thyroid disorder to determine if it continued to change with age after 55 years. Two hundred and ninety cases of hyperthyroidism presenting after the age of 55 years without a previous history of goitre, collected in the Department of Nuclear Medicine of the Pitié Hospital between January 1976 and May 1980, were analysed retrospectively. There was no significant correlation between age and heart rate or total circulating thyroxine (T4) and triiodothyronine (T3) concentration. A positive correlation with weight loss and a negative correlation with I 131 fixation were observed. It was higher in cases of atrial fibrillation and hyperthyroidism with normal thyroid scintigraphy. Graves' disease with goitre was associated with the most overt signs of thyrotoxicosis and the highest hormonal concentrations, contrarily to toxic adenoma. The T3 but not T4 concentration correlated positively with heart rate. T3 and T4 were positively correlated with weight loss, and this correlation remained significant at constant T4 and T3 concentrations.

Age Factors↗

Mitochondrial DNA sequences of primates: tempo and mode of evolution.

We cloned and sequenced a segment of mitochondrial DNA from human, chimpanzee, gorilla, orangutan, and gibbon. This segment is 896 bp in length, contains the genes for three transfer RNAs and parts of two proteins, and is homologous in all 5 primates. The 5 sequences differ from one another by base substitutions at 283 positions and by a deletion of one base pair. The sequence differences range from 9 to 19% among species, in agreement with estimates from cleavage map comparisons, thus confirming that the rate of mtDNA evolution in primates is 5 to 10 times higher than in nuclear DNA. The most striking new finding to emerge from these comparisons is that transitions greatly outnumber transversions. Ninety-two percent of the differences among the most closely related species (human, chimpanzee, and gorilla) are transitions. For pairs of species with longer divergence times, the observed percentage of transitions falls until, in the case of comparisons between primates and non-primates, it reaches a value of 45. The time dependence is probably due to obliteration of the record of transitions by multiple substitutions at the same nucleotide site. This finding illustrates the importance of choosing closely related species for analysis of evolutionary process. The remarkable bias toward transitions in mtDNA evolution necessitates the revision of equations that correct for multiple substitutions at the same site. With revised equations, we calculated the incidence of silent and replacement substitutions in the two protein-coding genes. The silent substitution rate is 4 to 6 times higher than the replacement rate, indicating strong functional constraints at replacement sites. Moreover, the silent rate for these two genes is about 10% per million years, a value 10 times higher than the silent rate for the nuclear genes studied so far. In addition, the mean substitution rate in the three mitochondrial tRNA genes is at least 100 times higher than in nuclear tRNA genes. Finally, genealogical analysis of the sequence differences supports the view that the human lineage branched off only slightly before the gorilla and chimpanzee lineages diverged and strengthens the hypothesis that humans are more related to gorillas and chimpanzees than is the orangutan.

Animals↗

The transposition properties of Tn2 in E. coli.

We report the characterization of Tn2 transpositions into the chromosome and into an F' lacproB episome of E. coli. When Tn2 transposes into the chromosome a proportion of the insertions result in auxotrophy. These insertions can revert to prototrophs and lose ampicillin resistance concomitantly. However, Tn2 insertions in F' lacproB are often associated with deletions, and it seems probable that insertion and deletion occur simultaneously.

Ampicillin↗

The structure of a DNA unwinding protein and its complexes with oligodeoxynucleotides by x-ray diffraction.

The structure of the gene 5 DNA unwinding protein from bacteriophage fd has been solved to 2.3 A resolution by x-ray diffraction techniques. The molecule contains an extensive cleft region that we have identified as the DNA binding site on the basis of the residues that comprise its surface. The interior of the groove has a rather large number of basic amino acid residues that serve to draw the polynucleotide backbone into the cleft. Arrayed along the external edges of the groove are a number of aromatic amino acid side groups that are in position to stack upon the bases of the DNA and fix it in place. The cleft then acts as an elongated pair of jaws that draws the DNA between them by charge interactions involving the phosphates with the interior lysines and arginines. The jaws then close on the DNA strand through small conformation changes and the rotation of aromatic side-chains into position to stack upon the purines and pyrimidines. Complexes of the gene 5 protein with a variety of oligodeoxynucleotides have been formed and crystallized for x-ray diffraction analysis. The crystallographic parameters of four different unit cells indicate that the fundamental unit of the complex is composed of six gene 5 protein dimers. We believe this aggregate has 622 point group symmetry and is a ring formed by end to end closure of a linear array of six dimers. From our results we have proposed a double helical model for the gene 5 protein-DNA complex in which the protein forms a spindle or core around which the DNA is spooled. 5.0-A x-ray diffraction data from one of the crystalline complexes is currently being analyzed by molecular replacement techniques to obtain what we believe will be the first direct visualization of a protein-deoxyribonucleic acid complex approaching atomic resolution.

Coliphages↗

Proteus vulgaris agglutination by cystic fibrosis sera.

The factor in sera of patients with cystic fibrosis (CF) and their parents which agglutinates Proteus vulgaris has characteristics similar to those of IgG antibody to this organism. Sera of patients without CF who have P. vulgaris infections agglutinate the organism similarly. At present there are too many false-positives in a control population for the test to be widely useful for heterozygote identification.

Adult↗

Antiglobulin antibody in the sera of contacts of children with leukaemia.

Healthy adults (parents, neighbours, and hospital staff) in close contact with children with leukaemia were found to have a high incidence of positive latex agglutination antiglobulin tests (probably an IgM antiglobulin antibody). This may explain a previous report of a high incidence of IgM anti-EB virus antibodies in parents of leukaemic children, which our results did not confirm (IgM antiglobulin, reacting with IgG anti-EB virus, could have been misinterpreted as IgM anti-EB virus). The antiglobulin antibody probably represents a nonspecific response to an infective agent. Other hospital staff, including those exposed to nonleukaemic children with infections, had a much lower incidence of the antibody, and it may represent a response to the leukaemic process itself, rather than to the infections to which such children are prone. Some leukaemic children have a similar antibody.

Adolescent↗

Influenzal acute myositis in the elderly.

We report an 84-year-old man with completely regressive acute myositis. The presumed etiology was an Influenza A virus infection, based on the serologic results.

Acute Disease↗