Smad7 is inactivated through a direct physical interaction with the LIM protein Hic-5/ARA55.

We recently reported that hydrogen peroxide-inducible clone-5 (Hic-5, also named androgen receptor-associated protein 55) can bind to the transforming growth factor-beta (TGF-beta)-signaling regulator Smad3, thereby inhibiting certain Smad3-dependent TGF-beta responses. We now show that Hic-5 can also control TGF-beta responses through an alternative mechanism involving Smad7, a key negative regulator of TGF-beta signaling. Hic-5 binds directly to Smad7. This interaction requires the LIM3 domain of Hic-5, and enhances TGF-beta signaling through causing loss of Smad7 protein but not mRNA. Enforced expression of Hic-5 reverses the ability of Smad7 to suppress TGF-beta-induced phosphorylation of Smads 2 and 3 and activation of the plasminogen activator inhibitor-1 promoter (in NRP-154 and PC3 prostate carcinoma and WPMY-1 prostate myofibroblast cell lines). Lentiviral-mediated small-hairpin RNA silencing of endogenous Hic-5 reduced TGF-beta responses in PC3 and WPMY-1 cells. Further work suggests that the level of Smad7 is modulated by its physical interaction with Hic-5 and targeted to a degradation pathway not likely to be proteasomal. Our findings support that Hic-5 functions as a cell-type-specific activator of TGF-beta signaling through its ability to physically interact with and neutralize Smad7.

Rb/E2F4 and Smad2/3 link survivin to TGF-beta-induced apoptosis and tumor progression.

Survivin is a prosurvival protein overexpressed in many cancers through mechanisms that remain poorly explored, and is implicated in control of tumor progression and resistance to cancer chemotherapeutics. Here, we report a critical role for survivin in the induction of apoptosis by transforming growth factor-beta (TGF-beta). We show that TGF-beta rapidly downregulates survivin expression in prostate epithelial cells, through a unique mechanism of transcriptional suppression involving Smads 2 and 3, Rb/E2F4, and the cell-cycle repressor elements CDE and CHR. This TGF-beta response is triggered through a Smad2/3-dependent hypophosphorylation of Rb and the subsequent association of the Rb/E2F4 repressive complex to CDE/CHR elements in the proximal region of the survivin promoter. Viral-mediated gene delivery experiments, involving overexpressing or silencing survivin, reveal critical roles of survivin in apoptosis induced by TGF-beta alone or in cooperation with cancer therapeutic agents. We propose a novel TGF-beta/Rb/survivin axis with a putative role in the functional switch of TGF-beta from tumor suppressor to tumor promoter.

MR imaging of the thoracoabdominal junction.

Recent advances in MR imaging techniques and its multiplanar capability allow for improved detection and characterization of benign and malignant processes occurring in the thoracoabdominal region. It is important to the staging process of patients with known malignancy to correctly diagnose incidental masses in this region, including hepatic or adrenal lesions, which initially may be identified by other imaging modalities. MR imaging provides a complimentary role in lesion detection and diagnosis that may ultimately affect therapeutic management and outcome.

Liver and bone window settings for soft-copy interpretation of chest and abdominal CT.

OBJECTIVE: We evaluated whether the use of multiple window and level settings on a soft-copy workstation improves diagnostic accuracy on chest and abdominal CT. We hypothesized that routinely using window and level settings during soft-copy interpretation would beneficially affect the final diagnosis without compromising efficiency. MATERIALS AND METHODS: Two hundred three randomly selected abdominal and chest CT scans were interpreted by three radiologists using a four-monitor soft-copy workstation (images per screen, nine; resolution, 2K). After the initial interpretations, all scans were reevaluated by the same radiologists using additional liver and bone window and level settings. Differences in conspicuity and characterization of abnormalities were graded on a three-point scale. RESULTS: Conspicuity and characterization of abnormalities were improved in 67% of abnormal findings (81/121; p = 0.01). Improvement (a finding that substantially affected the final diagnosis) was present in 18% of abnormal findings (22/121; p = 0.04). On average, the evaluation of images at multiple window and level settings required an additional 40 sec per case. CONCLUSION: The use of multiple window and level settings during soft-copy interpretation resulted in improved lesion detectability and characterization with greater diagnostic efficacy. Using soft-copy workstations, radiologists can evaluate images using multiple settings without compromising efficiency.

Imaging features of posttransplantation lymphoproliferative disorder in pancreas transplant recipients.

OBJECTIVE: The purpose of this study was to describe the imaging features of posttransplant lymphoproliferative disorder (PTLD) in pancreas transplant recipients. CONCLUSION: The prominent image finding of PTLD in pancreas transplant recipients is diffuse allograft enlargement, an appearance that may be indistinguishable from the image findings of acute pancreatitis or transplant rejection. However, failure of response to immunosuppressive therapy, presence of intraallograft or extraallograft focal masses, or organomegaly may suggest the diagnosis of PTLD.

MR imaging of prostate cancer.

MR imaging technology is continually evolving and improving. Endorectal MR imaging provides excellent anatomic detail and is the most accurate imaging modality for staging prostate cancer with the ability to affect therapy and cure in many men. Failure to detect microscopic disease and microscopic capsular invasion remain significant weaknesses. MR spectroscopy has great potential for improving the sensitivity and specificity of MR imaging and expanding its diagnostic and staging usefulness.

Percutaneous abdominal and pelvic interventional procedures using CT fluoroscopy guidance.

OBJECTIVE: The purpose of our study was to assess the use of low-milliamperage CT fluoroscopy guidance for percutaneous abdominopelvic biopsy and therapeutic procedures. MATERIALS AND METHODS: We reviewed the clinical records and relevant imaging studies of 97 patients who underwent 119 percutaneous CT fluoroscopy-guided abdominal or pelvic procedures: fluid collection aspiration or drainage catheter insertion (n = 59), biopsy (n = 49), hepatocellular carcinoma ethanol ablation (n = 6), chemoneurolysis (n = 4), and brachytherapy catheter insertion (n = 1). These procedures were guided using a helical CT scanner providing real-time fluoroscopy reconstruction at six frames per second. A control panel and video monitor beside the gantry allowed direct operator control during all interventional procedures. RESULTS: One hundred twelve (94.1%) procedures were successfully performed using either a stand-off needle holder and continuous real-time CT fluoroscopy guidance or incremental manual insertion and intermittent CT fluoroscopy to confirm position. Image quality using low milliamperage was adequate for needle or drainage tube placement in all but two low-contrast liver lesions. Two hematomas were accessed but yielded no fluid on aspiration; one drainage procedure was abandoned after the patient developed endotoxic shock. Imaging of ethanol distribution during injection facilitated tumor ablation and neurolytic procedures. CT fluoroscopy allowed rapid assessment of needle, guidewire, dilator, and catheter placement, especially in nonaxial planes. Average CT fluoroscopy time for biopsy and therapeutic procedures was 133 sec (range, 35-336 sec) and 186 sec (range, 20-660 sec), respectively. CONCLUSION: CT fluoroscopy is a practical clinical tool that facilitates effective performance of percutaneous abdominal and pelvic interventional procedures.

MammoWeb continuing medical education (CME): a web-based breast imaging CME program.

The ubiquity of the world-wide web allows unique educational opportunities for continuing medical education (CME). We have designed a comprehensive breast imaging CME curriculum to permit individual physicians in their homes or offices to use personal computers to ease the burden of this process. Category 1 CME credits can be earned off-hours without having the physician travel out of town. In addition, since the course is computer-based, the overall costs to the participant are substantially reduced. The program can be updated on an ongoing basis to include new technology or to provide additional information requested by the users.

Acute pancreatic transplant rejection: evaluation with dynamic contrast-enhanced MR imaging compared with histopathologic analysis.

PURPOSE: To evaluate the use of dynamic contrast material-enhanced gradient-recalled-echo MR imaging for the diagnosis of acute pancreatic transplant rejection, as confirmed at histopathologic analysis. MATERIALS AND METHODS: Thirty MR imaging studies were performed in 25 patients within 3 days of percutaneous biopsy or pancreatectomy. The mean percentage of parenchymal enhancement (MPPE) at dynamic contrast-enhanced MR imaging was calculated. RESULTS: Biopsy findings were no evidence of rejection (n = 7 [23%]), mild rejection (n = 10 [33%]), moderate (n = 6 [20%]) and severe (n = 2 [7%]) acute rejection, and infarction (n = 5 [17%]). The corresponding MPPEs at 1 minute were 106%, 66%, 62%, 57%, and 3%, respectively. Overlap of cases in the normal and rejection groups occurred; however, using an MPPE cutoff of 100% resulted in a sensitivity of 96%. An MPPE over 120% was seen in the normal group only. The MPPE was significantly greater in the normal group than in the rejection or infarction group (P < .05). CONCLUSION: Dynamic contrast-enhanced MR imaging is highly sensitive for the detection of acute pancreatic transplant rejection. Because of overlap of cases in the normal and rejection groups, percutaneous biopsy may be needed in some cases. Pancreatic allografts with infarction can be clearly identified.

Evaluation of biopsy needles and prototypic needle guide devices for percutaneous biopsy with CT fluoroscopic guidance in simulated organ tissue.

The authors evaluated accuracy and success rates for placement of fine-aspiration, core, and coaxial biopsy needles in pork meat with three needle guide devices and computed tomographic fluoroscopic guidance. Accuracy and reliability with a metallic sponge-forceps needle holder was equal to or greater than those with other devices, and it was preferred by operators due to its lighter weight and single-handed manipulation. All needle holders functioned poorly with thin-walled needles.

Frequency of abdominal CT findings in AIDS patients with M. avium complex bacteraemia.

BACKGROUND: Use of blood culture studies for early diagnosis of Mycobacterium avium complex (MAC) infection has become important due to the recent development of effective antibiotic therapy for this condition. This study assessed the abdominal computed tomography (CT) findings in patients with AIDS who presented with bacteraemic MAC infection. METHODS: A retrospective analysis of abdominal CT scans was performed in 24 patients who presented with MAC-positive blood culture. CT images were reviewed specifically to evaluate for lymph node enlargement and attenuation, hepatomegaly, splenomegaly, bowel wall abnormality and for any other pathological changes. Comparison was made to prior reports of the CT findings in this disease process. RESULT: Enlarged intra-abdominal mesenteric and/or retroperitoneal lymph nodes were found in 10 patients (42%). These nodes were characterized by homogeneous, soft-tissue attenuation in eight of the 10 patients. Hepatomegaly, splenomegaly and small bowel wall thickening were noted in 12 (50%), 11 (46%) and four (14%) patients, respectively. CT findings were evaluated as normal in six (25%) patients. CONCLUSIONS: Enlarged mesenteric and/or retroperitoneal lymph nodes in AIDS patients with bacteraemic MAC were observed much less frequently on CT than previously reported in AIDS patient populations. Normal abdominal CT findings do not exclude this diagnosis and may reflect a trend towards earlier detection of MAC disease.

Torsion of intraperitoneal renal transplants: imaging appearances.

OBJECTIVE: Torsion of a renal transplant is a rare complication with nonspecific clinical manifestations. Prompt detection is necessary to allow surgical treatment and to preserve renal function. We describe the radiologic appearances of torsion of intraperitoneal renal transplants in patients who have undergone simultaneous renal and pancreatic transplantation or dual renal transplantation. CONCLUSION: Renal transplant torsion should be suspected when a change in renal axis associated with abnormal perfusion occurs in an intraperitoneal kidney.

MR imaging of the adrenal gland: radiologic-pathologic correlation.

Complex physiologic and neoplastic processes affect the adrenal glands. An appreciation of the gross pathologic and histologic correlates of disease aids in understanding the mechanisms by which diagnostic imaging helps characterize adrenal masses. Computed tomographic (CT) densitometry and chemical shift magnetic resonance (MR) imaging would seem to be the most reliable tools in determining whether a given adrenal mass is specifically an adenoma. Such a determination is made on the basis of the presence of substantial amounts of intracytoplasmic lipid. Thus, although a homogeneous mass with a CT attenuation of less than 10 HU or a decrease in signal intensity at opposed-phase MR imaging is diagnostic for adenoma, lesions that do not have these features are indeterminate and may necessitate biopsy. Adrenal myelolipoma also has a distinctive imaging appearance that reflects the presence of macroscopic fat deposits. Diagnosis of adenoma or adrenal myelolipoma is very helpful in the assessment and treatment of asymptomatic patients with adrenal masses and may make biopsy unnecessary. In patients with clinical or biochemical evidence of adrenal disease, MR imaging helps confirm the presence of a mass and allows localization and further characterization of the lesion.

Clinical pathway for enhanced parent and preterm infant interaction through parent education.

The article discusses the importance of implementing a clinical pathway in the neonatal intensive care unit that emphasizes parent education. Through an extensive literature review, a clinical path was developed that incorporates parent education through an individualized, developmentally supportive model of interaction. The clinical path is designed to be utilized as a teaching tool from birth to discharge from the hospital. The path can serve as a guide for teaching and identifying learning objectives a long a time line as well as for providing consistent documentation.

Creating a digital video-based teaching file for interventional procedures using CT fluoroscopy.

A computerized radiology education teaching file application, MRW (Multimedia Radiology Workstation), was produced in our department as a collaboration of faculty, fellows and a doctoral student. This inexpensive and flexible system is novice-programmable and is capable of capturing images from multiple modalities (including still and cine image) and organizing them into individual electronic teaching cases. Help and tutorial functions support the main case display functions.

End stage renal transplant failure: allograft appearances on CT.

INTRODUCTION: Failed renal allografts often are left in situ in patients who revert to chronic dialysis therapy or who undergo retransplantation. These patients may be investigated with computed tomography (CT) imaging for allograft-related or other abdominopelvic disease. This study describes the appearances of failed renal transplants on CT. METHODS: A retrospective study was made of the clinical records and CT findings on 25 studies in 14 patients, 5-156 months (average, 44 months) following allograft failure. CT studies were reviewed for allograft position, size, shape, attenuation value, calcification, cyst formation, related abdominopelvic findings and the presence of other allografts. Correlation was made with clinical findings in all patients and with pathological findings in six. RESULTS: Global shrinkage was noted in eight failed allografts, all of which were asymptomatic. Enlargement of two failed allografts was due to symptomatic acute infarction of the allograft in one patient and subacute haemorrhagic infarction simulating a tumour mass in another. CT attenuation values in individual allografts varied markedly due to fatty replacement, hydronephrosis, haemorrhage or dense calcification. Both a failed longstanding and a functioning more recently placed renal allograft were present in seven patients, four of whom had acute complications related to the more recently transplanted kidney. Two of six calcified allografts were mistaken for opacified bowel on CT. CONCLUSION: A wide spectrum in size, shape and attenuation values may be detected in failed renal allografts by CT. These organs may be the site of acute disease despite their lack of physiological function or may be diagnostically confusing findings in patients with acute disease related to more recently transplanted organs.