PhD

thesis1. The carbohydrate components of human gamma-globulin, fraction II-1,2 were identified and quantitatively estimated. 2. Three glycopeptides were isolated from a papain digest of human gamma-globulin and characterized by chemical and physical methods. 3. The amino acid of the three glycopeptides was determined. 4. The three glycopeptides were found to represent a single carbohydrate group which was attached to the protein by a single aspartic acid residue. The carbohydrate group contained 3 galactose, 5 mannose, 2 fucose, 6 to 8 glucosamine, and 2 sialic acid residue. 5. The significance of these findings was discussed in relation to glycol-proteins and antibodies

Solution Structures of the C-Terminal Domain of Cardiac Troponin C Free and Bound to the N-Terminal Domain of Cardiac Troponin I

The N-terminal domain of cardiac troponin I (cTnI) comprising residues 33−80 and lacking the cardiac-specific amino terminus forms a stable binary complex with the C-terminal domain of cardiac troponin C (cTnC) comprising residues 81−161. We have utilized heteronuclear multidimensional NMR to assign the backbone and side-chain resonances of Ca2+-saturated cTnC(81−161) both free and bound to cTnI(33−80). No significant differences were observed between secondary structural elements determined for free and cTnI(33−80)-bound cTnC(81−161). We have determined solution structures of Ca2+-saturated cTnC(81−161) free and bound to cTnI(33−80). While the tertiary structure of cTnC(81−161) is qualitatively similar to that observed free in solution, the binding of cTnI(33−80) results mainly in an opening of the structure and movement of the loop region between helices F and G. Together, these movements provide the binding site for the N-terminal domain of cTnI. The putative binding site for cTnI(33−80) was determined by mapping amide proton and nitrogen chemical shift changes, induced by the binding of cTnI(33−80), onto the C-terminal cTnC structure. The binding interface for cTnI(33−80), as suggested from chemical shift changes, involves predominantly hydrophobic interactions located in the expanded hydrophobic pocket. The largest chemical shift changes were observed in the loop region connecting helices F and G. Inspection of available TnC sequences reveals that these residues are highly conserved, suggesting a common binding motif for the Ca2+/Mg2+-dependent interaction site in the TnC/TnI complex

Cost effectiveness of initiating dialysis early: A randomized controlled trial

Background: Planned early initiation of dialysis therapy based on estimated kidney function does not influence mortality and major comorbid conditions, but amelioration of symptoms may improve quality of life and decrease costs. Study Design: Patients with progressive chronic kidney disease and a Cockcroft-Gault estimated glomerular filtration rate of 10-15 mL/min/1.73 m were randomly assigned to start dialysis therapy at a glomerular filtration rate of either 10-14 (early start) or 5-7 mL/min/1.73 m (late start). Setting & Population: Of the original 828 patients in the IDEAL (Initiation of Dialysis Early or Late) Trial in renal units in Australia and New Zealand, 642 agreed to participate in this cost-effectiveness study. Study Perspective & Timeframe: A societal perspective was taken for costs. Patients were enrolled between July 1, 2000, and November 14, 2008, and followed up until November 14, 2009. Intervention: Planned earlier start of maintenance dialysis therapy. Outcomes: Difference in quality of life and costs. Results: Median follow-up of patients (307 early start, 335 late start) was 4.15 years, with a 6-month difference in median duration of dialysis therapy. Mean direct dialysis costs were significantly higher in the early-start group ($10,777; 95$313 to $22,801). Total costs, including costs for resources used to manage adverse events, were higher in the early-start group ($18,715; 95% CI, -$3,162 to$43,021), although not statistically different. Adjusted for differences in baseline quality of life, the difference in quality-adjusted survival between groups over the time horizon of the trial was not statistically different (0.02 full health equivalent years; 95% CI, -0.09 to 0.14). Limitations: Missing quality-of-life questionnaires and skewed cost data, although similar in each group, decrease the precision of results. Conclusion: Planned early initiation of dialysis therapy in patients with progressive chronic kidney disease has higher dialysis costs and is not associated with improved quality of life