Faculty Bibliography

In this study we present data on the spatial relationship between neural crest-derived cells (NCC) and the specialized cardiac conduction system (CCS) in the developing murine heart. Using Wnt1-Cre/R26R conditional reporter mice that express beta-galactosidase from ROSA26 upon Cre-mediated recombination, two populations of NCC are seen: one migrates through the arterial pole and contributes to the bundle branches, whereas the second population enters by way of the venous pole and provides cells to the sinoatrial and atrioventricular node areas. The CCS/ lacZ construct is found in the myocardium of the early embryonic heart and afterward only persists in the definitive CCS and is acknowledged as a reporter for the developing conduction system. The contiguous expression of both reporters is suggestive for a potential role of cardiac NCC in the induction of the final differentiation of the CCS

The use of five histochemical stains (cresyl violet, thionin, hematoxylin & eosin, silver stain, and acridine orange) was evaluated in combination with an expression profiling paradigm that included regional and single cell analyses within the hippocampus of post-mortem human brains and adult mice. Adjacent serial sections of human and mouse hippocampus were labeled by histochemistry or neurofilament immunocytochemistry. These tissue sections were used as starting material for regional and single cell microdissection followed by a newly developed RNA amplification procedure (terminal continuation (TC) RNA amplification) and subsequent hybridization to custom-designed cDNA arrays. Results indicated equivalent levels of global hybridization signal intensity and relative expression levels for individual genes for hippocampi stained by cresyl violet, thionin, and hematoxylin & eosin, and neurofilament immunocytochemistry. Moreover, no significant differences existed between the Nissl stains and neurofilament immunocytochemistry for individual CA1 neurons obtained via laser capture microdissection. In contrast, a marked decrement was observed in adjacent hippocampal sections stained for silver stain and acridine orange, both at the level of the regional dissection and at the CA1 neuron population level. Observations made on the cDNA array platform were validated by real-time qPCR using primers directed against beta-actin and glyceraldehyde-3 phosphate dehydrogenase. Thus, this report demonstrated the utility of using specific Nissl stains, but not stains that bind RNA species directly, in both human and mouse brain tissues at the regional and cellular level for state-of-the-art molecular fingerprinting studies

Amyloid-associated protein (AA)-type systemic amyloidosis has been referred to as secondary amyloidosis because it is secondary to an associated inflammatory condition. It is extremely rare in patients with non-Hodgkin's lymphoma (NHL). Here we report an autopsy case of follicular small cleaved cell lymphoma with focal large B-cell lymphoma transformation in association with systemic AA-type amyloidosis. Formalin-fixed, paraffin-embedded tissues from autopsy and the patient's previous surgical specimen were studied by Congo red stain; electron microscopy; and immunostaining with antibodies against AA protein, P component, and kappa and lambda light chains. There was a marked AA amyloid deposition in the glomeruli of both kidneys, the retroperitoneal lymphoma mass, the blood vessels, the adrenal glands, and the adipose tissues. The patient's previous surgical specimens were negative for amyloid. We propose that this patient's systemic AA-type amyloidosis developed along the course of his NHL

The fission yeast Schizosaccharomyces pombe rad9 gene promotes cell survival through activation of cell cycle checkpoints induced by DNA damage. Mouse embryonic stem cells with a targeted deletion of Mrad9, the mouse ortholog of this gene, were created to evaluate its function in mammals. Mrad9(-/-) cells demonstrated a marked increase in spontaneous chromosome aberrations and HPRT mutations, indicating a role in the maintenance of genomic integrity. These cells were also extremely sensitive to UV light, gamma rays, and hydroxyurea, and heterozygotes were somewhat sensitive to the last two agents relative to Mrad9(+/+) controls. Mrad9(-/-) cells could initiate but not maintain gamma-ray-induced G(2) delay and retained the ability to delay DNA synthesis rapidly after UV irradiation, suggesting that checkpoint abnormalities contribute little to the radiosensitivity observed. Ectopic expression of Mrad9 or human HRAD9 complemented Mrad9(-/-) cell defects, indicating that the gene has radioresponse and genomic maintenance functions that are evolutionarily conserved. Mrad9(+/-) mice were generated, but heterozygous intercrosses failed to yield Mrad9(-/-) pups, since embryos died at midgestation. Furthermore, Mrad9(-/-) mouse embryo fibroblasts were not viable. These investigations establish Mrad9 as a key mammalian genetic element of pathways that regulate the cellular response to DNA damage, maintenance of genomic integrity, and proper embryonic development

PURPOSE: To retrospectively compare quantitative and qualitative methods of assessing magnetic resonance (MR) imaging contrast enhancement as the basis for diagnosing renal malignancy. MATERIALS AND METHODS: MR imaging was performed by using a gadolinium-enhanced breath-hold fat-suppressed three-dimensional T1-weighted gradient-echo sequence in 71 patients (48 men and 23 women; mean age, 62 years; age range, 26-87 years) with 93 renal lesions for which pathologic correlation was available. For quantitative measurements of enhancement, the relative increase in signal intensity values was measured by one investigator with manually defined regions of interest, and the threshold of an increase of 15% or greater was used to distinguish malignant from benign masses. For qualitative assessment, two investigators independently reviewed the subtracted images of all lesions and subjectively determined whether enhancement was present or absent. The sensitivity, specificity, and positive and negative predictive values for each method were calculated and compared. Mean (+/- standard deviation) and median values of relative enhancement were also calculated for benign and malignant lesions. RESULTS: At pathologic analysis, 74 (80%) of the 93 lesions were malignant, and 19 (20%)-including seven oncocytomas-were benign. For diagnosing malignancy based on enhancement alone, sensitivity and specificity, respectively, were 95% (70 of 74 lesions) and 53% (10 of 19 lesions) at quantitative analysis and 99% (73 of 74 lesions) and 58% (11 of 19 lesions) at qualitative analysis. All seven oncocytomas were considered to be malignant with both methods. When the oncocytomas were excluded, specificities increased to 83% (10 of 12 lesions) and 92% (11 of 12 lesions) for the quantitative and qualitative evaluations, respectively. Three of the four malignant lesions incorrectly characterized as benign at quantitative assessment were hyperintense on unenhanced MR images; all were diagnosed correctly at qualitative evaluation. CONCLUSION: Image subtraction enables accurate assessment of renal tumor enhancement, particularly in the setting of masses that are hyperintense on unenhanced MR images

MR imaging is the only noninvasive test that may provide a complete picture of renal status with minimal risk to the patient, simultaneously improving diagnosis and lowering costs. This article reviews several MR renography techniques, including approaches for quantifying renal perfusion and glomerular filtration rate. Also discussed are clinical applications for the diagnosis and follow-up of renovascular disease, hydronephrosis,and renal transplant dysfunction. The article concludes with an overview of technical problems and challenges facing MR renography

Our objective was to investigate the coexistence of vascular and biliary anatomic variants, the latter of which are known to increase the risk of biliary complications in living liver donor transplantation. A total of 108 consecutive liver donor candidates were examined by magnetic resonance (MR) imaging that included 2 MR cholangiography methods, T2-weighted MR cholangiography and mangofodipir-enhanced T1-weighted three-dimensional (3D) MR cholangiography, as well as gadolinium-enhanced MR angiography and venography of the liver. Images were interpreted by at least 2 investigators in consensus for definition of hepatic arterial, portal venous, and biliary anatomy. A subset of 51 subjects underwent laparotomy for right hepatectomy. Of the 108 subjects examined, 50 (46%) demonstrated normal hepatic artery, portal vein, and biliary anatomy. Variants of the hepatic artery were found in 27 of 108 (25%) subjects, of the portal vein in 12 of 108 (11%) subjects, and of the bile ducts in 30 of 108 (28%) subjects. Of the 27 subjects with hepatic arterial variants, 8 (30%) also had variant biliary anatomy. The association between hepatic arterial variants and biliary variants was not statistically significant (P >.5). However, of the 12 subjects with portal vein variants, 7 (58%) had biliary variants, and in 6 of 7 cases, the right posterior hepatic duct was anomalous. By chi-square analysis, the association between portal venous and biliary variants was significant (P =.012). In conclusion, over half of subjects with portal vein variants were found to have anomalous biliary anatomy, which always involved the hepatic ducts of the right lobe. The association between portal venous and biliary variants is statistically significant, while there is no significant association between hepatic arterial and biliary variants

MR imaging is useful in differentiating and characterizing renal masses. A careful evaluation of the signal characteristics and morphology of a renal mass combined with the ancillary imaging findings and patient history should assist the radiologist in making the proper diagnosis or recommending the appropriate treatment in most cases. This pictorial essay demonstrates the typical MR imaging features of common renal masses including renal cell carcinoma (RCC), oncocytoma, angiomyolipoma, metastases, transitional cell carcinoma (TCC), lymphoma, and arteriovenous malformation (AVM), and highlights several potential diagnostic pitfalls in making the proper diagnosis

MRI may be used for detecting cartilage invasion in patients with laryngeal carcinoma. However, the normal laryngeal ossification pattern has not been studied. Our purpose was to examine the normal age-related signal patterns in the cricoid, thyroid and arytenoid cartilages on T1-weighted images. Signal in the cartilages was assessed by two radiologists in a blinded fashion using three-point scales for intensity and symmetry. Statistical analysis consisted of logistic and monotonic regression. There was excellent interobserver agreement (>85%) for all categories. The cartilages predominantly ossify symmetrically and the extent of high signal from all three increases with age. The latter may help in detection of cartilage invasion by tumor in older patients. Normal symmetry may be helpful when comparing sides for tumor invasion