Dynamic in vivo interactions among Myc network members.

Members of the Myc oncoprotein network (c-Myc, Max, and Mad) play important roles in proliferation, differentiation, and apoptosis. We expressed chimeric green fluorescent protein (GFP) fusions of c-Myc, Max, and three Mad proteins in fibroblasts. Individually, c-Myc and Mad proteins localized in subnuclear speckles, whereas Max assumed a homogeneous nuclear pattern. These distributions were co-dominant and dynamic, however, as each protein assumed the pattern of its heterodimeric partner when the latter was co-expressed at a higher level. Deletion mapping of two Mad members, Mad1 and Mxi1, demonstrated that the domains responsible for nuclear localization and speckling are separable. A non-speckling Mxi1 mutant was also less effective as a transcriptional repressor than wild-type Mxi1. c-Myc nuclear speckles were distinct from SC-35 domains involved in mRNA processing. However, in the presence of co-expressed Max, c-Myc, but not Mad, co-localized to a subset of SC-35 loci. These results show that Myc network proteins comprise dynamic subnuclear structures and behave co-dominantly when co-expressed with their normal heterodimerization partners. In addition, c-Myc-Max heterodimers, but not Max-Mad heterodimers, localize to foci actively engaged in pre-mRNA transcription/processing. These findings suggest novel means by which Myc network members promote transcriptional activation or repression.

Making the transition: the role of helical CT in the evaluation of potentially acute thoracic aortic injuries.

OBJECTIVE: The purpose of this study was to show that helical CT could be used at our center in lieu of routine aortography to examine patients who have had serious blunt chest trauma. We also wanted to assess the potential savings of using CT to avoid unnecessary aortography. MATERIALS AND METHODS: The institutional review board approved the parallel imaging-CT immediately followed by aortography-of patients presenting with blunt chest trauma between August 1997 and August 1998. To screen patients for potential aortic injuries, we performed parallel imaging on 142 patients, and these patients comprised our patient population. CT examinations of the patients were reviewed for signs of injury by radiologists who were unaware of each other's interpretations and the aortographic results. Findings of CT examinations were classified as negative, positive, or inconclusive for injury. Aortography was performed immediately after CT. The technical and professional fees for both transcatheter aortography and helical CT were also compared. RESULTS: Our combined kappa value for all CT interpretations was 0.714. The aortographic sensitivity and negative predictive value were both 100%. Likewise, the sensitivity and negative predictive value of CT were 100%. The total costs of performing aortography were estimated at approximately $402,900, whereas those for performing helical CT were estimated at $202,800. CONCLUSION: Helical CT has a sensitivity and negative predictive value equivalent to that of aortography. Using CT to eliminate the possibility of mediastinal hematoma and to evaluate the cause of an abnormal aortic contour in a trauma patient allows us to use aortography more selectively. Avoiding the performance of unnecessary aortography will expedite patient care and reduce costs. We report the results of our experience with CT and how our center successfully made this transition in the initial examination of patients with serious thoracic trauma.

Promotion of growth and apoptosis in c-myc nullizygous fibroblasts by other members of the myc oncoprotein family.

c-myc nullizygous fibroblasts (KO cells) were used to compare the abilities of c-myc, N-myc and L-myc oncoproteins to accelerate growth, promote apoptosis, revert morphology, and regulate the expression of previously described c-myc target genes. All three myc oncoproteins were expressed following retroviral transduction of KO cells. The proteins all enhanced the growth rate of KO cells and significantly shortened the cell cycle transition time. They also accelerated apoptosis following serum deprivation, reverted the abnormal KO cell morphology, and modulated the expression of previously described c-myc target genes. In most cases, L-myc was equivalent to c-myc and N-myc in restoring all of the c-myc-dependent activities. These findings contrast with the previously reported weak transforming and transactivating properties of L-myc. Myc oncoproteins may thus impart both highly similar as well as dissimilar signals to the cells in which they are expressed.

Intensive radiation therapy concurrent with up to 7-week continuous-infusion paclitaxel for locally advanced solid tumors: phase I studies.

Patients with locally advanced solid tumors of the lung, head and neck, and malignant astrocytomas usually succumb to their disease despite aggressive standard therapy. Laboratory data suggest that the addition of 1.0 to 10 nmol/L paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), a microtubule stabilizing drug, to radiation therapy may result in significant radiation sensitization, perhaps due to accumulation of cells at G2/M. Relatively low concentrations (1.0 to 10 nmol/L) appear to be optimal for direct cytotoxicity and radiosensitization in vitro. Within this dose range, more prolonged exposure seems to result in higher response rates. The phase I trials reported here are designed to test the combination of paclitaxel, administered by continuous intravenous infusion (24 hours a day, 7 days a week), and standard, curative-intent radiation therapy. The ultimate goal of this study is to improve local and systemic control and survival for patients with these three tumor types. To date, 39 evaluable patients are enrolled in this study; there has been no dose-limiting toxicity up to 6.5 mg/m2/d. Observed toxicities include anemia, lymphopenia, mucositis, and cutaneous toxicities.

Application of a classical model of competitive business strategy to orthodontic practice.

This study explored how market forces might affect the business aspects of orthodontic practices; in particular, profitability. The forces identified were (1) intensity of rivalry, (2) threat of new entrants, and (3) bargaining power of buyers and suppliers. A mail survey instrument was used to collect the data. Results showed that more than half the surveyed practices show an increase in new case starts despite weak economic conditions. Although satellite offices and marketing increase the overhead, they do not add to net profit. New entrants are a threat to existing practices, as are the substitute discretionary spending by the consumer. Interestingly, while some orthodontic practices have joined the managed care programs, a majority of them realize neither increased patient load nor profit. Our data seem to indicate that orthodontic practices have not been successful in "cost containment" with their marketing, number of employees, computerization or inventory. Collectively, the results of this study suggest that success in an orthodontic office is primarily dependent on the practitioner's personality traits, rather than rigidly applied business principles.

Anterior clear space: how clear? How often? How come?

PURPOSE: To compare the opacity of the retrosternal clear space with that of the retrocardiac region on normal lateral chest radiographs, to measure the clear space, and to evaluate the reasons for these findings. MATERIALS AND METHODS: Left lateral chest radiographs and computed tomographic scans of 38 patients with normal studies were evaluated and the results were correlated. RESULTS: In 19 (50%) patients, retrosternal and retrocardiac opacity were equal. In 16 (42%), the retrosternal region was more opaque than the retrocardiac region (10 of 12 women, six of 26 men). The difference between the sexes was statistically significant (P = .002). In only nine (24%) patients was the anterior margin of the ascending aorta defined on the lateral study. Mean sternum-to-aorta distance in these patients was 29 mm. CONCLUSIONS: Retrosternal opacity greater than retrocardiac opacity on lateral chest radiographs is a frequent normal finding, especially in women. Sternum-to-aorta distance may be difficult to measure, and distance greater than 2.5 cm may be normal in some persons.

Chronic traumatic pseudoaneurysm of the thoracic aorta: a report of two cases following gunshot injury.

Gunshot injury to the thoracic aorta is nearly always fatal. Although the victim usually will succumb to exsanguination or tamponade in the minutes following injury, unusual cases of occult injury occur when a pseudoaneurysm, occlusion, or fistula forms at the site of injury. We report two patients with gunshot injury to the thoracic aorta that resulted in chronic pseudoaneurysms that went undetected for 325 and 46 days, respectively. Computed tomography and aortography were utilized to verify these pseudoaneurysms, and both patients underwent successful surgical repair.

Cardiac valve reconstruction and replacement: a brief review.

Surgical methods for improving the function of diseased cardiac valves are valve reconstruction (valvuloplasty) and valve replacement with mechanical prostheses, biologic prostheses, or homograft (donor) valves. Reconstruction is used primarily for incompetent mitral and tricuspid valves and addresses each part of the valve apparatus individually. Annuloplasty rings are often used to restore the size and shape of the valve orifice. Long-term anticoagulation therapy is not necessary. The designs of mechanical prostheses have evolved since the early caged-ball prostheses. Current models are noted for their durability. Patients who undergo implantation of these prostheses must also undergo long-term anticoagulation therapy. Biologic prostheses made from porcine valves or bovine pericardium are not as durable as their mechanical counterparts, but they do not require long-term anticoagulation therapy. Homografts are used in relatively few centers. They have good hemodynamics and do not necessitate long-term anticoagulation therapy. Radiologists should be familiar with the radiographic appearance of the various valve prostheses and annuloplasty rings and with the advantages and disadvantages of their use in cardiac valvular surgery.

"Hyperdense" aortic wall: potential pitfall in CT screening for aortic dissection.

Opacity of the aortic wall as compared with the nonopacified blood in the lumen has been utilized as one of the criteria for the diagnosis of aortic dissection. It has also been suggested that this finding may be indicative of severe anemia. We evaluated the frequency and implications of aortic wall hyperdensity in 107 consecutive chest CT examinations in patients with no indication of aortic dissection clinically or by other imaging modalities, and whose hematocrit was known. The density of the wall correlated with the patient's age and presence of calcification. Presence or absence of anemia was not a statistically significant factor, although marked conspicuousness of the wall below the age of 60 years did suggest anemia. Atherosclerosis is the most likely explanation for wall visibility in nonanemic patients.

Apparatus seen on chest radiographs after cardiac surgery in adults.

The authors review the purpose, radiographic appearance, and possible complications of various tubes, catheters, and wires seen on chest radiographs after cardiac surgery. Drainage tubes, temporary epicardial wire electrodes, surgical clips, intraaortic counterpulsation balloon, atrial pressure monitor catheters, and sternal wires are reviewed. Because recent articles have discussed the Swan-Ganz catheter and automatic implantable cardioverter defibrillator, these are not covered in depth.

Mediastinal histoplasmosis granuloma: evaluation with CT.

Mediastinal granuloma secondary to histoplasmosis was described in three patients. Computed tomographic scans in each patient demonstrated a large, low-attenuation mediastinal mass crossed by enhancing septae. Other granulomatous diseases may produce similar abnormalities. The differential diagnosis of such lesions was discussed.

Benign esophagorespiratory fistulas in adults.

Four benign esophagorespiratory fistulas, three secondary to granulomatous disease and one presumed to be congenital, have been diagnosed in adults at the authors' institution in the past year. The patients had symptoms of chronic or recurrent pulmonary infections, and two experienced coughing after swallowing. Chest radiographs demonstrated refractory consolidation, with or without cavitation and frequently accompanied by an air-distended esophagus. Barium studies were diagnostic. All patients responded well to antibiotic and surgical therapy.

Mediastinal carinal bronchogenic cyst: is its mere presence an indication for surgical excision?

A notion has prevailed that carinal bronchogenic cyst and other congenital mediastinal cystic lesions, particularly those occurring in older children and adults, are usually asymptomatic, innocuous, and frequently only an incidental finding on routine chest roentgenogram or postmortem examination. Some physicians, therefore, have adopted a policy of observation for these patients. Our experience, however, as demonstrated in three cases reported herein, and the experience of others, clearly shows that carinal bronchogenic cyst is far from being usually asymptomatic and innocuous, but in fact often produces a broad spectrum of clinical manifestations, some of which are life-threatening. Mere observation not only places these patients at serious risk, but also increases the possibility of missed diagnosis and delayed treatment of those lymphoproliferative malignancies involving mediastinal lymph nodes that can mimic a carinal bronchogenic cyst. Computerized tomography (CT) is the single most important method of making a diagnosis of carinal bronchogenic cyst. We believe strongly that the mere presence of a mediastinal carinal bronchogenic cyst is an indication for surgical excision.

Dental benefits and reimbursements.

This article analyzes and compares the various dental benefit reimbursement methodologies currently available in the dental marketplace. Emphasis is placed on the advantages and disadvantages of the capitation/HMO approach from the point of view of the patient, dentist, plan administrator, and purchaser/employer.

Retrocardiac phantom image on hypocycloidal chest tomograms.

A phantom image produced by displaced blur margins of the cardiac silhouette and mimicking a paraspinous retrocardiac mass was noted in 50% of 125 hypocycloidal full chest tomograms. It was reproduced on tomograms of a chest phantom. Careful comparison with routine posteroanterior and lateral chest radiographs prevents misinterpretation.

Another look at the "ring-around-the-artery" in pneumomediastinum.

Gas surrounding the right pulmonary artery has been observed in three patients, including two in whom it was demonstrated around the intrapericardial right pulmonary artery on frontal films. This would provide a pathway for occasional development of spontaneous pneumopericardium.

Blunt traumatic rupture of the right hemidiaphragm: experience in 12 patients.

In a 9-year period (1972 to 1981), 35 patients with blunt traumatic rupture of the diaphragm were seen in our institution; 12 had involvement of the right hemidiaphragm, an incidence of approximately 34%. In 9 of these 12 patients, the right-sided diaphragmatic injuries were seen soon after the accident (acute), and in 3, late after the accident (chronic). A large diaphragmatic rent, usually 10 cm or more, without any predilection to a specific area of the right hemidiaphragm, was a frequent operative finding. Expectedly, the most common viscus that was injured or herniated through the defect was the liver. Total or nearly total herniation of the liver was noted in 5 patients and partial herniation, in 1. Injury to the juxtahepatic vena cava or hepatic vein, or both, was also encountered in 5 patients. This highly lethal injury accounted for the 3 deaths in the series, all of which were directly related to an uncontrollable exsanguinating hemorrhage from the injured vena cava or hepatic vein. The surgical approach for repair of a ruptured right hemidiaphragm is best individualized. The right thoracotomy approach through a right posterolateral incision is preferred for chronic diaphragmatic injury. It is also our choice in patients in whom acute right-sided injuries are definitively diagnosed and who are hemodynamically stable. This approach not only provided the best exposure of the defect, but also made the repair of associated retrohepatic caval injury surprisingly easy in at least 2 of our patients.(ABSTRACT TRUNCATED AT 250 WORDS)