Citations

Epimorphin (also known as syntaxin 2) acts as an epithelial morphogen when secreted by stromal cells of the mammary gland, lung, liver, colon, pancreas and other tissues, but the same molecule functions within the cell to mediate membrane fusion. How this molecule, which lacks a signal sequence and contains a transmembrane domain at the C-terminus, translocates across the plasma membrane and is secreted to become a morphogen, and how it initiates morphogenic events is not clear. Here, we show that epimorphin is secreted through a non-classical mechanism, similar to that previously described for secretion of the leaderless protein FGF1, and we identify the key molecular elements responsible for translocation and secretion from the cell. We also show that secreted epimorphin binds to αv-integrin-containing receptors on target epithelial cells, leading to activation of specific downstream signaling pathways and induction of epithelial morphogenesis. These findings provide key insight into how epimorphin functions as an epithelial morphogen.

Nitric oxide (NO) is a highly diffusible and short-lived physiological messenger. Despite its diffusible nature, NO modifies thiol groups of specific cysteine residues in target proteins and alters protein function via S-nitrosylation. Although intracellular S-nitrosylation is a specific posttranslational modification, the defined localization of an NO source (nitric oxide synthase, NOS) with protein S-nitrosylation has never been directly demonstrated. Endothelial NOS (eNOS) is localized mainly on the Golgi apparatus and in plasma membrane caveolae. Here, we show by using eNOS targeted to either the Golgi or the nucleus that S-nitrosylation is concentrated at the primary site of eNOS localization. Furthermore, localization of eNOS on the Golgi enhances overall Golgi protein S-nitrosylation, the specific S-nitrosylation of N -ethylmaleimide-sensitive factor and reduces the speed of protein transport from the endoplasmic reticulum to the plasma membrane in a reversible manner. These data indicate that local NOS action generates organelle-specific protein S-nitrosylation reactions that can regulate intracellular transport processes.

Background— Coronary bypass surgery (CABG) and angioplasty (PTCA) have been compared in several randomized trials, but data about long-term economic and quality-of-life outcomes are limited. Methods and Results— Cost and quality-of-life data were collected prospectively from 934 patients who were randomized in the Bypass Angioplasty Revascularization Investigation (BARI) and followed up for 10 to12 years. CABG had 53% higher costs initially, but the gap closed to <5% during the first 2 years; after 12 years, the mean cumulative cost of CABG patients was $123 000 versus $120 750 for PTCA, yielding a cost-effectiveness ratio of $14 300/life-year added. CABG patients experienced significantly greater improvement in their physical functioning for the first 3 years but not in later follow-up. Recurrent angina substantially reduced all quality-of-life measures throughout follow-up. Cumulative costs were significantly higher among patients with diabetes, heart failure, and comorbid conditions and among women; costs also were increased by angina, by the number of revascularization procedures, and among patients who died. Conclusion— Early differences between CABG and PTCA in costs and quality of life were no longer significant at 10 to 12 years of follow-up. CABG was cost-effective as compared with PTCA for multivessel disease.

Abstract OBJECTIVE AND IMPORTANCE Cerebellar hemorrhage remote from the site of surgery may complicate neurosurgical procedures. We describe our experience with two cases of cerebellar hemorrhage after spinal surgery and review the three cases previously reported in the literature to determine whether these cases provide insight regarding the pathogenesis of remote cerebellar hemorrhage. CLINICAL PRESENTATION One of our patients developed cerebellar hemorrhage in the vermis and right hemisphere after transpedicular removal of a partially intradural T9–T10 herniated disc with the patient in the prone position. The other patient developed cerebellar hemorrhage in the vermis and bilateral hemispheres after L3–S1 decompression and instrumentation with the patient in the prone position, during which the dura was inadvertently opened. INTERVENTION The first patient was treated conservatively and had mild residual dysarthria and gait ataxia 2 months after surgery. The second patient underwent exploration and revision of the lumbar wound with primary dural repair. The cerebellar hemorrhage was treated conservatively, and the patient had mild dysarthria and ataxia 1 month after surgery. CONCLUSION Cerebellar hemorrhage must be considered in patients with unexplained neurological deterioration after spinal surgery. Dural opening with loss of cerebrospinal fluid has occurred in every reported case of cerebellar hemorrhage complicating a spinal procedure, supporting the hypothesis that loss of cerebrospinal fluid is central to the pathogenesis of this condition. Because remote cerebellar hemorrhage can occur after procedures with the patient in the supine, sitting, and prone positions, patient positioning seems unlikely to play a causative role in its occurrence.

ABSTRACT OBJECTIVE Remote cerebellar hemorrhage (RCH) is an infrequent and poorly understood complication of supratentorial neurosurgical procedures. We retrospectively compared 42 patients who experienced RCH with a case-matched control cohort, to delineate risk factors associated with the occurrence of this complication. METHODS Between 1988 and 2000, 42 patients experienced RCH after supratentorial neurosurgical procedures at our institution. Diagnoses were made on the basis of postoperative computed tomographic or magnetic resonance imaging findings in all cases. The medical records for these patients were reviewed and compared with those for a control cohort of 43 patients, matched for age, sex, surgical lesion, and type of craniotomy, who were treated during the same period. RESULTS RCH most commonly occurred after frontotemporal craniotomies for unruptured aneurysm repair or temporal lobectomy and was frequently an incidental finding on postoperative computed tomographic scans. However, some cases of RCH were associated with significant morbidity, and two patients died. Preoperative aspirin use and elevated intraoperative systolic blood pressure were significantly associated with RCH (P = 0.026 and P = 0.036, respectively). Pathological findings for two cases demonstrated hemorrhagic infarctions in both. CONCLUSION RCH most commonly follows supratentorial neurosurgical procedures, performed with the patient in the supine position, that involve opening of cerebrospinal fluid cisterns or the ventricular system (such as unruptured aneurysm repair or temporal lobectomy). Preoperative aspirin use and moderately elevated intraoperative systolic blood pressure are potentially modifiable risk factors associated with the development of RCH. Although RCH can cause death or major morbidity, most cases are asymptomatic or exhibit a benign course. Cerebellar “sag” as a result of cerebrospinal fluid hypovolemia, causing transient occlusion of superior bridging veins within the posterior fossa and consequent hemorrhagic venous infarction, is the most likely pathophysiological cause of RCH.

OBJECTIVEThis study reviewed patients with unilateral facial paralysis and normal clinical and imaging findings who underwent diagnostic facial nerve exploration.STUDY DESIGN AND SETTINGFifteen patients with facial paralysis and normal findings were seen in the Mayo Clinic Department of Otorhinolaryngology.RESULTSEleven patients were misdiagnosed as having Bell palsy or idiopathic paralysis. Progressive facial paralysis with sequential involvement of adjacent facial nerve branches occurred in all 15 patients. Seven patients had a history of regional skin squamous cell carcinoma, 13 patients had surgical exploration to rule out a neoplastic process, and 2 patients had negative exploration. At last follow‐up, 5 patients were alive.CONCLUSIONSPatients with facial paralysis and normal clinical and imaging findings should be considered for facial nerve exploration when the patient has a history of pain or regional skin cancer, involvement of other cranial nerves, and prolonged facial paralysis.SIGNIFICANCEOccult malignancy of the facial nerve may cause unilateral facial paralysis in patients with normal clinical and imaging findings. (Otolaryngol Head Neck Surg 2004;130:459–65.)