Faculty Bibliography

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

OBJECTIVE: To provide background and evaluate the role of herpesviruses in benign lymphoepithelial cysts (BLC) of the parotid gland. STUDY DESIGN: Case series derived from review of pathology specimens. METHODS: Radiolabeled polymerase chain reaction (PCR) analysis was used to detect for the presence of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpes virus 8 (HHV-8) DNA sequences in 14 paraffin embedded specimens and 1 freshly aspirated BLC specimen. Thirteen normal parotid tissue specimens obtained from paraffin embedded blocks were used as a control group. RESULTS: CMV was detected with nearly equal frequency between the two groups (23% of normal vs. 20% in BLC). HHV-8 was found in 13% of the BLC group and in none of the normal group (P =.4841). There was significant difference in EBV detection between the normal (0%) and the BLC (33%) groups (P =.0437). CONCLUSION: CMV and HHV-8 does not appear to be associated with BLCs. Although EBV is found more frequently in BLC than in normal parotid controls, further studies are needed to elucidate the role of this virus in BLC pathogenesis

We present a new technique that uses a custom-built ink-jet printer to fabricate precise micropatterns of cell adhesion materials for neural cell culture. Other work in neural cell patterning has employed photolithography or "soft lithographic" techniques such as micro-stamping, but such approaches are limited by their use of an un-alterable master pattern such as a mask or stamp master and can be resource-intensive. In contrast, ink-jet printing, used in low-cost desktop printers, patterns material by depositing microscopic droplets under robotic control in a programmable and inexpensive manner. We report the use of ink-jet printing to fabricate neuron-adhesive patterns such as islands and other shapes using poly(ethylene) glycol as the cell-repulsive material and a collagen/poly-D-lysine (PDL) mixture as the cell-adhesive material. We show that dissociated rat hippocampal neurons and glia grown at low densities on such patterns retain strong pattern adherence for over 25 days. The patterned neurons are comparable to control, un-patterned cells in electrophysiological properties and in immunocytochemical measurements of synaptic density and inhibitory cell distributions. We suggest that an inexpensive desktop printer may be an accessible tool for making micro-island cultures and other basic patterns. We also suggest that ink-jet printing may be extended to a range of developmental neuroscience studies, given its ability to more easily layer materials, build substrate-bound gradients, construct out-of-plane structure, and deposit sources of diffusible factors.