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At least 73 records · Page 4Linked to original sources
PubMed1994

Localization of the binding site on plasma kallikrein for high-molecular-weight kininogen to both apple 1 and apple 4 domains of the heavy chain.

The C-terminal end of the heavy chain of human plasma prekallikrein or kallikrein contains a binding site for high-molecular-weight kininogen, the nonenzymatic procofactor of contact activation. To further map this binding site, a series of overlapping peptides were synthesized. The amount of kallikrein that bound to kininogen-coated microtiter plate wells in the presence of increasing concentrations of each peptide was determined by kallikrein amidolytic activity. A peptide encompassing Lys266-Gly295 of kallikrein, conformationally constrained by a disulfide bond, displayed the lowest Kd value (approximately 67 microM). The linear peptide, Leu262-Gly295, displayed lower affinity (129 microM). N-terminal or C-terminal truncation/extension peptides of this sequence diminished binding activity. Since the closely related protein, factor XI, has been shown to bind kininogen, a kallikrein-based peptide (Phe56-Gly86) homologous to the binding domain of FXI, was examined and found to possess less, but significant, binding affinity for kininogen (Kd 530 microM). Isothermal titration calorimetry was used to assess binding between the kallikrein-based peptides and a peptide encompassing the kallikrein binding domain in kininogen (Ser565-Lys595). Leu262-Gly295 possesses potent binding activity (Kd 52 microM), while Phe56-Gly86 displays poorer binding activity (Kd 400 microM). These interactions are endothermic and entropically favored, suggesting that a conformational rearrangement takes place upon binding. We conclude that the binding site for kininogen within prekallikrein is composed of discontinuous linear segments that form a contiguous surface in the folded protein.

Amino Acid Sequence↗
PubMedDate not supplied

Choosing between apples and apples: physicians' choices of prescription drugs that have similar side effects and efficacies.

OBJECTIVE: To examine physician choices of commonly used medications having similar side effects and efficacies, and to evaluate factors that may affect these choices. DESIGN/SETTING: Cross-sectional survey conducted in winter 1989-1990. PARTICIPANTS: 263 physicians at a university teaching hospital (response rate = 71%). MEASUREMENTS AND MAIN RESULTS: Physicians rated patient compliance, cost to patient, and patient preference as the three most influential factors in their selection of a particular agent from a class of similar drugs. Housestaff were less likely than faculty to consider cost to patient as a "very important" factor (33% vs. 60%; p less than 0.05), and only 11% of all physicians felt that cost to third-party payer was very important. Physicians reported that their choices of particular nonsteroidal anti-inflammatory drugs (NSAIDs), histamine-2 (H2) blockers, and inhaled beta-agonists were mainly determined by which drugs enhanced compliance or were used by others (the "traditional choice"); cost to patient was a less important influence in these instances. All physician subgroups were inaccurate in predicting the approximate prices of their first- and second-choice agents. For example, only 28% of those selecting naproxen as their preferred NSAID were within $10 of the range of the prices of a one-month supply, and 14% were within $10 for cimetidine. CONCLUSION: Although this group of physicians reported considering drug costs to be important when choosing between similar drugs, they acknowledged that cost was relatively unimportant in several specific instances studied and their knowledge of the absolute and relative prices of drugs they commonly prescribed was deficient.

Adrenergic beta-Agonists↗
PubMed2002

Comparing apples to apples: the relative financial performance of Manitoba's acute care hospitals.

This paper presents comparative financial ratios that can be adopted by health system administrators and policy analysts to begin to evaluate the performance of acute care hospitals. We combined financial, statistical and clinical information for 73 acute care hospitals in Manitoba for fiscal 1997/98 to calculate 15 indicators of financial performance. Our findings suggest that there is variability between hospital types in their average costs per weighted case, cost structure and financial performance.

Acute Disease↗
PubMed2002

Comparing apples with apples in clinical populations: applications of the adjusted Clinical Group System in British Columbia.

This article reviews the Adjusted Clinical Group Case-Mix System and describes how it is being applied in the management of physician services in British Columbia. Developed in the United States for management and research, adjusted clinical groups are used to measure the illness burden and health service needs of individuals and, when aggregated, of populations, by grouping the range of conditions coded on physician claims and hospital care records over a defined time period, typically one year. In Canadian and United States settings, adjusted clinical groups are up to five times more predictive of ambulatory resource use than are age and sex groups alone. The article describes how adjusted clinical groups are being applied to adjust capitation payments for physician groups in British Columbia's Primary Care Demonstration Project and profiles of physician practice activity.

Ambulatory Care↗
PubMed2006

Apples to apples: improving the performance of motif finders and their significance analysis in the Twilight Zone.

MOTIVATION: Effective algorithms for finding relatively weak motifs are an important practical necessity while scanning long DNA sequences for regulatory elements. The success of such an algorithm hinges on the ability of its scoring function combined with a significance analysis test to discern real motifs from random noise. RESULTS: In the first half of the paper we show that the paradigm of relying on entropy scores and their E-values can lead to undesirable results when searching for weak motifs and we offer alternate approaches to analyzing the significance of motifs. In the second half of the paper we reintroduce a scoring function and present a motif-finder that optimizes it that are more effective in finding relatively weak motifs than other tools. AVAILABILITY: The GibbsILR motif finder is available at http://www.cs.cornell.edu/~keich.

Algorithms↗