Hepatocyte growth factor (HGF) is a plasminogen-like protein thought to be a humoral mediator of liver regeneration. A 145-kilodalton tyrosyl phosphoprotein observed in rapid response to HGF treatment of intact target cells was identified by immunoblot analysis as the beta subunit of the c-met proto-oncogene product, a membrane-spanning tyrosine kinase. Covalent cross-linking of 125I-labeled ligand to cellular proteins of appropriate size that were recognized by antibodies to c-met directly established the c-met product as the cell-surface receptor for HGF.

BACKGROUND Accurately estimating surgical risks is critical for shared decision making and informed consent. The Centers for Medicare and Medicaid Services may soon put forth a measure requiring surgeons to provide patients with patient-specific, empirically-derived estimates of postoperative complications. Our objectives were (1) to develop a universal surgical risk estimation tool, (2) to compare performance of the universal vs. prior procedure-specific Surgical Risk Calculators, and (3) to allow surgeons to empirically adjust the estimates of risk. STUDY DESIGN Using standardized clinical data from 393 ACS NSQIP hospitals, a web-based tool was developed to allow surgeons to easily enter 21 preoperative factors (demographics, comorbidities, procedure). Regression models were developed to predict 8 outcomes based on the preoperative risk factors. The universal model was compared to procedure-specific models. To incorporate surgeon input, a subjective Surgeon Adjustment Score, allowing risk estimates to vary within the estimate's confidence interval, was introduced and tested with 80 surgeons using 10 case scenarios. RESULTS Based on 1,414,006 patients encompassing 1,557 unique CPT codes, a universal Surgical Risk Calculator model was developed which had excellent performance for mortality (c-statistic=0.944; Brier=0.011[ where scores approaching zero are better]), morbidity (c-statistic=0.816, Brier=0.069), and 6 additional complications (c-statistics>0.8). Predictions were similarly robust for the universal calculator vs. procedure-specific calculators (e.g., colorectal). Surgeons demonstrated considerable agreement on the case scenario scoring (80-100% agreement), suggesting reliable score assignment between surgeons. CONCLUSIONS The ACS NSQIP Surgical Risk Calculator is a decision-support tool based on reliable multi-institutional clinical data which can be used to estimate the risks of most operations. The ACS NSQIP Surgical Risk Calculator will allow clinicians and patients to make decisions using empirically derived, patient-specific postoperative risks.

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The tyrosine kinasee activity of p60c-src, the protein product of the c-src gene, increases during mitosis; this may be important in initiating at least some of the cellular changes that occur during this phase of the cell cycle. Although there is evidence that p60c-src is phosphorylated at several sites during mitosis, phosphorylation in vitro does not increase its kinase activity. We now report that the kinase activity of a p60c-src mutant with residue tyrosine 527 changed to phenylanine does not change during the cell cycle, suggesting that changes in the phosphorylation state of this residue may be responsible for the activation of p60c-src at mitosis. Although changes in phosphorylation at Tyr 527 cannot be detected with the wild-type protein we find that phosphorylation at Tyr 527 of a mutant with reduced kinase activity decreases threefold during mitosis. On the basis of these results we suggest that activation of p60c-src at mitosis results from decreased phosphorylation on Tyr 527, and that p60c-src may be or may activate the kinase that phosphorylates Tyr 527.