K-Ras associates with the plasma membrane (PM) through farnesylation that functions in conjunction with an adjacent polybasic sequence. We show that phosphorylation by protein kinase C (PKC) of S181 within the polybasic region promotes rapid dissociation of K-Ras from the PM and association with intracellular membranes, including the outer membrane of mitochondria where phospho-K-Ras interacts with Bcl-XL. PKC agonists promote apoptosis of cells transformed with oncogenic K-Ras in a S181-dependent manner. K-Ras with a phosphomimetic residue at position 181 induces apoptosis via a pathway that requires Bcl-XL. The PKC agonist bryostatin-1 inhibited the growth in vitro and in vivo of cells transformed with oncogenic K-Ras in a S181-dependent fashion. These data demonstrate that the location and function of K-Ras are regulated directly by PKC and suggest an approach to therapy of K-Ras-dependent tumors with agents that stimulate phosphorylation of S181.
Background: Duodenal diverticuli are present in up to 22% of the population. However, perforation of a duodenal diverticulum with spillage of enteric contents into the retroperitoneum is rare. Methods: We report three cases of perforated duodenal diverticulitis. Results: Clinical presentations varied widely from patients with acute abdominal findings and generalized sepsis to a patient with mild symptoms of abdominal discomfort. CT scanning was the imaging modality used to make an accurate diagnosis. Treatment approaches for the most stable patient included nonoperative management with antibiotics, bowel rest and parenteral alimentation, while the less stable patients underwent definitive surgery with complete diversion of gastric contents and biliary flow from the affected area of duodenum. Conclusions: This report highlights the salient issues in the presentation, diagnosis and modern management of patients with this potentially catastrophic disease.
Introduction Positioning of implant components for total hip arthroplasty (THA) is important for polyethylene liner wear, prosthesis joint stability, and range of motion. The introduction of fluoroscopy for the direct anterior approach has been shown to improve physician accuracy for component positioning. Few studies compare the use of intraoperative fluoroscopy for THA component positioning in posterior THA. The purpose of this project is to retrospectively evaluate the effect of intraoperative fluoroscopy on component positioning for THA using posterior and direct anterior approach (DAA). Materials and Methods A retrospective review of postoperative weight-bearing X-ray films of THAs was performed over a 2-year period where a single fellowship–trained total joint surgeon introduced direct anterior approach into his practice while expanding the intraoperative use of fluoroscopy for all THA procedures, regardless of approach. Component position was evaluated through radiographic measurement of acetabular cup inclination (goal of 40 degrees), limb length discrepancy (goal of 0 mm), and femoral component offset difference (goal of 0 mm). Radiographic analysis was performed by two independent providers. Statistical analysis was performed using Student’s t-tests. Results A total of 107 patients with an average age of 62 years were identified during the 2-year period surrounding the THA practice change, adding fluoroscopy to posterior and DAA THA. Three cohorts were identified: cohort A: 44 patients who underwent posterior THAs without the use of intraoperative fluoroscopy, cohort B: 35 patients who underwent direct anterior approach THAs with the use of intraoperative fluoroscopy, and cohort C: 18 patients who underwent posterior THAs with the use of intraoperative fluoroscopy. The use of intraoperative fluoroscopy for the posterior approach versus unguided posterior approach increased accuracy of both cup inclination (44 degrees vs 50 degrees, P < .05) and femoral offset (4 mm vs 7 mm, P < .05). A comparison of DAA with fluoroscopy versus posterior approach without fluoroscopy showed improvement in cup inclination (48 degrees vs 50 degrees, P < .05). Fluoroscopy with posterior approach versus fluoroscopy with DAA was found to have improved cup inclination (44 degrees vs 48 degrees, P < .05). Conclusion Intraoperative use of fluoroscopy can improve component positioning for posterior THA.
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