Refining the classification of chest pain: a logical next step in the evaluation of patients for acute cardiac ischemia in the emergency department.
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Biomedical subjects
Publications and source records attributed to T J Ryan.
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Patients with chronic lymphoedema are prone to develop chronic infections and various tumours in the lymphoedematous limb, suggesting that regional immune surveillance is impaired. To test the hypothesis that cutaneous cell-mediated immunity is impaired, 35 women with postmastectomy lymphoedema were investigated using dinitrochlorobenzene to test the afferent and efferent loops of the allergic contact immune response. The results support the role of lymphatics as an important component of the immune response to allergens by the demonstration of impairment of both the afferent and efferent loops of the allergic contact dermatitis reaction, and confirm that there is suppression of immune competence in a lymphoedematous limb.
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A cDNA encoding human gamma-glutamyl hydrolase has been identified by searching an expressed sequence tag data base and using rat gamma-glutamyl hydrolase cDNA as the query sequence. The cDNA encodes a 318-amino acid protein of Mr 35,960. The deduced amino acid sequence of human gamma-glutamyl hydrolase shows 67% identity to that of rat gamma-glutamyl hydrolase. In both rat and human the 24 amino acids preceding the N terminus constitute a structural motif that is analogous to a leader or signal sequence. There are four consensus asparagine glycosylation sites in the human sequence, with three of them conserved in the rat enzyme. Expression of both the human and rat cDNA in Escherichia coli produced antigenically related proteins with enzyme activities characteristic of the native human and rat enzymes, respectively, when methotrexate di- or pentaglutamate were used as substrates. With the latter substrate the rat enzyme cleaved the innermost gamma-glutamyl linkage resulting in the sole production of methotrexate as the pteroyl containing product. The human enzyme differed in that it produced methotrexate tetraglutamate initially, followed by the triglutamate, and then the diglutamate and methotrexate. Hence the rat enzyme is an endopeptidase with methotrexate pentaglutamate as substrate, whereas the human enzyme exhibits exopeptidase activity. Another difference is that the expressed rat enzyme is equally active on methotrexate di- and pentaglutamate whereas the human enzyme has severalfold greater activity on methotrexate pentaglutamate compared with the diglutamate. These properties are consistent with the enzymes derived from human and rat sources.
Purified gamma-glutamyl hydrolase secreted from rat H35 hepatoma cells has been characterized as a diffuse band of 55 kDa on SDS-polyacrylamide gel electrophoresis that is converted to bands of 35 and 33 kDa after enzymatic removal of N-linked carbohydrate. Polyclonal antibodies against 55-kDa gamma-glutamyl hydrolase captured the enzyme activity and recognized the glycosylated and both deglycosylated forms of gamma-glutamyl hydrolase. A complete cDNA sequence of gamma-glutamyl hydrolase was obtained using degenerate oligonucleotides derived from peptide sequences, screening of a rat hepatoma cDNA library, and reverse transcription polymerase chain reaction. Based upon the deduced amino acid sequence the peptide component of gamma-glutamyl hydrolase had a molecular weight of 33,400. The results of amino acid analysis of the purified protein agreed with the deduced amino acid sequence in which there are seven potential asparagine-containing glycosylation sites.
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The results of early trials indicate that angioplasty during the first hours after MI onset has a lower incidence of reinfarction, intracranial hemorrhage, and death than does thrombolysis. In fact, results have been so good that the procedure has been approved for use in hospitals that do not have coronary bypass backup programs. Is angioplasty about to become the intervention of choice in acute MI?
Many prior studies involving a predominantly male population have demonstrated the importance of exercise test results in determining the outcome of patients with coronary artery disease. The prognostic significance of exercise testing in women is unknown. In our study, a total of 3,086 men and 747 women underwent maximal treadmill exercise testing, coronary angiography, and were prospectively followed for up to 16 years. They were divided into 3 groups (high, intermediate, and low risk) on the basis of exercise testing. Sixteen-year survival based on exercise test groups ranged from 38% to 61% in men and from 44% to 79% in women (p < 0.001). Among men, 12-year survival was enhanced by coronary artery bypass surgery versus medical therapy in the high-risk subgroup (69% vs 55%, respectively, p = 0.0025), but the 2 therapies were similar in the intermediate- and low-risk subgroups. Among women, neither medical nor surgical therapy resulted in improved 12-year survival rates in any of the 3 subgroups. These results suggest that exercise testing is helpful in assessing long-term survival in men and women. However, only exercise testing in men could identify a high-risk subset whose survival was enhanced by coronary artery bypass graft surgery.
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