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.

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.

Evaluation of ultrasound in the diagnosis of acute and chronic biliary tract disease.

Oral cholecystography and intravenous cholangiography are the two studies most frequently used to confirm the diagnosis of biliary tract disease. Since it is not always practical to obtain these in acutely ill patients, gray scale sonography was evaluated to determine its accuracy. One hundred eight patients had sonography performed prior to operation. The sonogram was correct in 96 of the 108 patients (89%). There were four false-negatives (3.7%), one false-positive (0.9%), and seven patients (6.4%) in whom the study was nondiagnostic. Stones were seen in 88 patients and confirmed in 87 patients for an accuracy of 98.9% Sonography is a simple, noninvasive procedure by which cholelithiasis can be accurately detected. Because of the high correlation between sonography and operative findings, we suggest that cholecystosonography be used as the initial screening study in patients suspected of having biliary tract disease.

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)

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.

Trichophyton verrucosum in Indiana. Infection in two cases.

Presented herein are two cases of dermatomycosis that occurred in Indiana. The causative agent in each case was Trichophyton verrucosum. The first patient had onychomycosis, tinea pedis, and tinea cruris. Although of long duration, his condition cleared readily after the administration of griseofulvin. The second patient, a recent immigrant from Yugoslavia, had erythematous, minimally scaling lesions was more typical, since T. verrucosum is commonly found on exposed parts of the skin. In this patient, also, lesions cleared after the administration of griseofulvin therapy.

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.

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.