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Biomedical subjects

A D Lee

Publications and source records attributed to A D Lee.

5 recordsLinked to original sources

The effects of multiple amino acid substitutions on the polypeptide backbone of tuna and horse cytochromes c.

The cytochromes c provide a wide range of natural and mutant homologous proteins which may be used to study structure/function relationships in biological electron-transfer reactions. A description of the cytochrome c structure has been provided by high-resolution X-ray crystallography for the cytochromes from tuna, bonito, rice and yeast (Saccharomyces iso-1). Correlation of these structures with NMR parameters is necessary to confirm the structure of the protein in solution and to permit the routine characterisation of cytochromes c with novel sequences. We have previously reported a method based on the analysis of pseudocontact shifts which allowed us to compare the conformations of some amino acid side chains of tuna cytochrome c in solution and in the crystalline state. Here we report a comparison of the conformations of the polypeptide backbone of cytochromes c in proteins from tuna and horse, using the chemical shifts of the amide NH and C alpha H protons. It is found that the backbone conformation and hydrogen-bond network is closely conserved between these proteins, despite 19 amino acid substitutions. Appreciable differences occur in two regions, around Asn 31 and at the beginning of the 60s helix. Evidence for some rotational or translational motion of the C-terminal helix is also presented.

Amino Acid Sequence

Contraction-mediated inactivation of glycogen synthase is accompanied by inactivation of glycogen synthase phosphatase in human skeletal muscle.

Activities of glycogen synthase (GS) and GS phosphatase were determined on human muscle biopsies before and after isometric contraction at 2/3 maximal voluntary force. Total GS activity did not change during contraction (4.92 +/- 0.70 at rest versus 5.00 +/- 0.42 mmol/min per kg dry wt.; mean +/- S.E.M.), whereas both the active form of GS and the ratio of active form to total GS decreased by approximately 35% (P less than 0.01). GS phosphatase was inactivated in all subjects by an average of 39%, from 5.95 +/- 1.30 to 3.63 +/- 0.97 mmol/min per kg dry wt. (P less than 0.01). It is suggested that at least part of the contraction-induced inactivation of GS is due to an inactivation of GS phosphatase.

Adult

Transient increase in glucose 1,6-bisphosphate in human skeletal muscle during isometric contraction.

Changes in glucose 1,6-bisphosphate and regulators of glucose-1,6-bisphosphate synthase and phosphatase during isometric contraction have been determined. Biopsies were obtained from the quadriceps femoris muscle before and after 20 s of contraction and at fatigue. Glucose 1,6-bisphosphate increased by 35% after 20 s of contraction (P less than 0.001) with no further change at fatigue (P greater than 0.05 versus 20 s). Pi, fructose 1,6-bisphosphate and glycerate 3-phosphate, all inhibitors of the synthase, increased significantly during the first 20 s (P less than 0.05-0.001), whereas muscle pH (decrease in which inhibits synthase) decreased continuously. The decrease in the total adenine nucleotide pool, which is stoichiometric with the increase in IMP (an activator of phosphatase), was not significant after 20 s, but was 15% at fatigue (P less than 0.001). The rapid increase in glucose 1,6-bisphosphate, despite increases in the inhibitors of synthase, suggests that the synthase was activated, possibly by the substrate glycerate 1,3-bisphosphate and/or a yet unknown activator(s). The lack of any further change in glucose 1,6-bisphosphate during the latter part of contraction may be due to concomitant activation of the synthase and phosphatase.

Adult

Amputation: two views.

It has been over one year now since his surgery, and Allen has returned to school and work, ambulating on his prosthesis most of the time. As his phantom limb pain decreased and his proficiency in walking increased, his acceptance of his amputation has been demonstrated in his comments and references to himself and his relations with others. As he states, the more comfortable he is about his amputation, the easier it is for others to accept and relate to him. This, I think, is the key to approaching that final stage of acceptance mentioned earlier. The more we can help our patients accept their amputation initially by supporting them through this crisis period, the easier it will be for them to relate to others and grow emotionally from these relationships.

Adaptation, Psychological

[Results of early thoracotomy in the treatment of non-calcified solitary pulmonary nodules. Analysis of 19 cases].

We reviewed 19 patients who had undergone thoracotomy and resection of a noncalcified solitary pulmonary nodule over the past 7 years, to see if a policy of early thoracotomy was therapeutically valid. The average age of patients was 50 (range 10 to 73 years), 6 females and 13 males. All of them asymptomatic. In this study, there were 9 (47.3%) of primary bronchogenic carcinoma, the incidence was 54.5% in patients above 50 years. There were no postoperative deaths and 3 serious postoperative complications (15.7%). Post operatory followed up by all patients ranged from one to seven years. The patients with benign lesions are all well. 9 of the cases had primary lung cancer, 2 died, 3 1/2 years and 5 years after surgery. We conclude that pre-operative differential diagnostic procedure between benign and malign nodules may not always be decisive, and that an early thoracotomy in indicated every case, since the incidence of malign tumors is frequent. Very small primary lung cancers detected and treated early do not have the same poor prognosis as larger primary cancers.

Adolescent