Effects of two major activating lesions on the structure and conformation of human ras oncogene products.

ras oncogenes are frequently activated in human tumors by mutations at codon 12 or 61 in their coding sequences. To investigate how these subtle alterations exert such profound effects on the biologic activities of these genes, we studied structural and conformational properties of human ras-oncogene-encoded 21-kDa proteins (p21s). We observed striking differences in the electrophoretic mobilities of the proteins under reducing and nonreducing conditions. These findings imply that intramolecular disulfide bonds affect native p21 conformation. The two activating lesions were shown to induce distinctly different alterations in p21 electrophoretic mobility that were unmasked only under reducing conditions. These results suggest that regions of the molecule containing such alterations are either not exposed or under conformational constraints in the native p21 molecule. We confirmed the opposing effects on protein mobility induced by the two activating lesions by using a recombinant gene containing both lesions. The recombinant gene's high-titer transforming activity further established that the two lesions do not negatively complement one another with respect to transforming-gene function. Our findings of distinct alterations in electrophoretic mobilities of position-12- and position-61-altered p21 molecules should be applicable to the rapid immunologic diagnosis of ras oncogenes in human malignancies.     

Pulmonary Metastasis From Breast Cancer With an 18-Year Disease-Free Interval: Implication of the Role of Surgery

The appearance of pulmonary metastasis more than 15 years after primary treatment for breast cancer is rare. We herein report the case of a breast cancer patient with solitary pulmonary metastasis, after an 18-year disease-free period, treated with resection. A 66-year-old Japanese woman was found to exhibit an abnormal shadow on a chest X-ray. She had undergone a left mastectomy for breast cancer 18 years previously. The nodule was suspected to be either metastatic or primary lung cancer, and thus thoracoscopic surgery was performed. The histologic diagnosis was metastasis from breast cancer. Pulmonary resection in breast cancer recurrence is an important diagnostic tool that allows for a differential diagnosis with primary lung cancer. The clinical implication of surgery for a solitary pulmonary metastasis from breast cancer is discussed in this report.     

Long-term outcome for surgically treated cervical spondylotic radiculopathy and myelopathy

Long-term follow-up results were examined to verify the efficacy of anterior osteophytectomy for cervical spondylotic myelopathy and radiculopathy, in particular the outcome for patients with developmentally narrow cervical canals and patients with associated ossification of the posterior longitudinal ligament (OPLL). One hundred thirty-nine patients who had undergone anterior osteophytectomy with interbody fusion between 1976 and 1990 were followed up for 1 to 22.5 years (mean 11.4 years). Overall results evaluated by the neurosurgical cervical spine scale scoring and grading showed significant improvement in both improvement score (2.7 +/- 2.3) and improvement rate (52.3 +/- 45.7%). Lower extremity motor function improved in 66.1% of patients, upper extremity motor function in 82.0%, and sensory/pain function in 70.5%. Improvement ranged from one to three grades. Severely affected patients showed good recovery. Outcome for patients with narrow cervical canals (41 patients, 29.5%) did not differ significantly from that for patients with normal canals (98, 70.5%). Patients with associated OPLL (32 patients, 23.0%) had approximately the same outcomes as those with only spondylosis (107, 77.0%). Fifteen patients (10.8%) underwent reoperation because of myelopathy due to disc degeneration adjacent to the fused level (11 patients) or OPLL (4 patients). Anterior osteophytectomy with interbody fusion can achieve good outcomes in patients with cervical spondylotic myelopathy and radiculopathy, regardless of the size of the spinal canal and association with OPLL.     

Autosynchronized systolic unloading during left ventricular assist with a centrifugal pump

OBJECTIVES: The purpose of this study was to investigate how the inflow cannulation site of the left ventricular assist system with a centrifugal pump would influence cardiac function on failing heart models. METHODS: In 10 sheep, a left ventricular assist system was instituted by an outflow cannula in the descending aorta, two inflow cannulas in the left atrium and the left ventricle, and connecting those cannulas to a magnetically suspended centrifugal pump. A conductance catheter and a tipped micromanometer for monitoring the pressure-volume loop were also inserted into the left ventricle. Myocardial oxygen consumption was directly measured. Heart failure was induced by injection of microspheres into the left main coronary artery. The assist rate was varied from 0% to 100% at each inflow cannulation site. RESULTS: The pump flow with left ventricular cannulation increased during the systolic phase and decreased during the diastolic phase, whereas it was constant with left atrial cannulation. Ejection fraction with left atrial cannulation decreased as the assist rate increased, whereas that with left ventricular cannulation was maintained up to 75% assist. The external work with left atrial cannulation decreased gradually as the assist rate increased, whereas the external work with left ventricular cannulation did not decrease until the assist rate reached 75%. The myocardial oxygen consumption in both cannulations decreased proportionally as the assist rate increased; they were significantly less with left ventricular cannulation at the 100% assist rate than with left atrial cannulation. CONCLUSION: Left ventricular cannulation during left ventricular assistance maintains ejection fraction and effectively reduces oxygen consumption.     

IgG-class anti-PF4/heparin antibodies and symptomatic DVT in orthopedic surgery patients receiving different anti-thromboembolic prophylaxis therapeutics

Background  

Heparin-induced thrombocytopenia (HIT) is a thromboembolic complication that can occur with unfractionated heparin (UFH) or low molecular weight heparin (LMWH). Our objective was to determine and compare the incidence of IgG-class HIT antibodies in patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) with different antithrombotic prophylaxis therapies and their contributions to the occurrence of venous thromboembolism (VTE).     

Three-dimensional computed tomography for lung cancer in a patient with three right vein ostia

Some variations in pulmonary vein anatomy can have serious consequences in patients undergoing lung surgery, but clinicians rarely encounter patients with these variations. We report here a thoracoscopic lobectomy for right lung cancer in a patient with three right vein ostia. Preoperative review of three-dimensional 64-row multidetector computed tomography (3D-MDCT) of the patient showed a variation that was not confirmed in transverse plane computed tomography films. However, the variant anomaly was confirmed during thoracoscopic right lower lobectomy. The postoperative course was uneventful, and the patient was discharged on postoperative day 10. Preoperative 3D-MDCT of the pulmonary vein produced a precise preoperative simulation for the surgeon and clearly showed the orientation of the patient’s vascular variant during surgery. This imaging technology contributes to safer thoracic surgery, especially thoracoscopic surgery.