Detection of O-Linked-N-Acetylglucosamine Modification and Its Associated Enzymes in Human Degenerated Intervertebral Discs

Study DesignHuman herniated discs were obtained from discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT).PurposeThis study aimed to quantify the extent of O-GlcNAcylation and its associated enzymes (OGT/OGA) in human degenerated intervertebral discs.Overview of LiteratureThe O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications are currently the focus of extensive research. O-GlcNAcylation is believed to contribute to the etiology of chronic illnesses by acting as a nutrient and stress sensor in the cellular environment. Mature intervertebral disc cells are chondrocyte-like cells, and O-GlcNAc has been shown to promote chondrocyte apoptosis in vitro. We believe that O-GlcNAcylation is a key regulator of disc degeneration.MethodsFifty-six specimens were fixed for 24 hours in a 10% solution of neutral-buffered formaldehyde, dehydrated, and embedded in paraffin. Tissue slices (4-µm-thick) were used for hematoxylin-eosin staining and immunohistochemistry.ResultsWe found that O-GlcNAcylation of cytoplasmic proteins was less than that of nuclear proteins in both single cells and cell clusters. Cytoplasmic O-GlcNAcylation occurs subsequent to nuclear O-GlcNAcylation and is directly proportional to disc degeneration. OGT and O-GlcNAc expression levels were identical in all specimens examined.ConclusionsO-GlcNAc and OGA/OGT expression is shown to correlate for the first time with intervertebral disc cell degeneration. Increasing disc degeneration is associated with increasing O-GlcNAcylation in both nuclear and cytoplasmic proteins in human disc cells

Incidental Non-Cardiac Findings of a Coronary Angiography with a 128-Slice Multi-Detector CT Scanner: Should We Only Concentrate on the Heart?

Objective: To evaluate the spectrum, prevalence, and significance of incidental non-cardiac findings (INCF) in patients referred for a non-invasive coronary angiography using a 128-slice multi-detector CT (MDCT). Materials and Methods: The study subjects included 1,044 patients; 774 males (mean age, 59.9 years) and 270 females (mean age, 63 years), referred for a coronary CT angiography on a 128-slice MDCT scanner. The scans were acquired from the level of the carina to just below the diaphragm. To evaluate INCFs, images were reconstructed with a large field of view (> 300 mm) covering the entire thorax. Images were reviewed in the axial, coronal, and sagittal planes, using the mediastinal, lung, and bone windows. The INCFs were classified as severe, indeterminate, and mild, based on their clinical importance, and as thoracic or abdominal based on their locations. Results: Incidental non-cardiac findings were detected in 56% of patients (588 of 1,044), including 435 males (mean age, 65.6 years) and 153 females (mean age, 67.9 years). A total of 729 INCFs were observed: 459 (63%) mild (58% thoracic, 43% abdominal), 96 (13%) indeterminate (95% thoracic, 5% abdominal), and 174 (24%) severe (87% thoracic, 13% abdominal). The prevalence of severe INCFs was 15%. Two severe INCFs were histologically verified as lung cancers. Conclusion: The 128-slice MDCT coronary angiography, in addition to cardiac imaging, can provide important information on the pathology of the chest and upper abdomen. The presence of severe INCFs is not rare, especially in the thorax. Therefore, all organs in the scan should be thoroughly evaluated in daily clinical practice

Association of Claudin-1 with E-Cadherin/Catenin Complex, Microvessel Density (MVD)-Related Markers, and Clinicopathological Features in Colorectal Carcinoma

Objectives: Intercellular adhesion mediated by claudin and cadherin/catenin complex is a prerequisite of epithelial integrity and differentiation and has been suggested to be frequently disturbed in cancers. Endoglin (CD105) has been shown to be a more useful marker to identify proliferating endothelium involved in angiogenesis than pan-endothelial markers such as CD31. The aim of this study was to assess the relationship between these markers and clinicopathological features of colorectal carcinomas. Materials and Methods: Surgical specimens from 69 patients with colorectal cancer were immunostained for claudin-1, E-cadherin, beta-catenin, endoglin and CD31. Results: Forty-six (66.7%), 67 (97.1%), and 67 (97.1%) of the tumors, expressed immunostaining for claudin-1, E-cadherin and beta-catenin, respectively. A significant association was seen between claudin-1 and E-cadherin expression (p=0.002), as well with beta-catenin (p=0.009). High beta-catenin expression appeared to reduce the risk of poor outcome. Endoglin vessel expression was correlated significantly with vessel invasion (p<0.0001), lymph node metastases (p=0.039), liver metastases (p<0.0001) and recurrence of the disease (p<0.010). Endoglin tumor cell expression was associated with E-cadherin and beta-catenin expression (p=0.001 and p=0.068), but not with claudin-1 expression (p=0.299). Conclusions: Loss of the expression of claudin-1, E-cadherin/beta-catenin downregulation, and high CD105-MVD counts may play a significant role in the high incidence of angiolymphatic invasion, metastases and prognosis in colorectal-cancer patients, but further studies are needed to clearly define their role in colorectal carcinoma. [J Interdiscipl Histopathol 2014; 2(3.000): 135-144

How reliable is MRCP with an SS-FSE sequence at 3.0 T: comparison between SS-FSE BH and 3D-FSE BH ASSET sequences

Purpose: The purpose of the present study was to evaluate the visibility and the image quality of the biliary and pancreatic duct system on magnetic resonance cholangiopancreatography (MRCP) images based on two breath-hold (BH) methods using array spatial sensitivity technique: a single-shot fast spin-echo (SS-FSE) sequence and a three-dimensional single slab fast spin-echo (3D-FSE) sequence. Materials and methods: In the present prospective comparative study, 47 patients (22 male and 25 female, mean age=50 years, age range=22-82 years) that were referred for MRCP during a 12-month period are included. All of them were referred with suspected pancreaticobiliary disease. All patients underwent MRCP with both a SS-FSE BH sequence and a 3D-FSE BH sequence. Qualitative evaluation regarding the depiction of three segments of the pancreaticobiliary tree and the frequency of artifacts was performed. Two radiologists graded each sequence of the obtained studies in a blinded fashion. Quantitative evaluation including calculation of relative signal intensity (rSI) and relative contrast (RC) ratios at seven segments of the pancreaticobiliary tree between fluid-filled ductal structures and organ parenchyma at the same ductal segments was performed. In order to evaluate the parameters' differences of the two sequences, either in qualitative or in quantitative analysis, the Wilcoxon paired signed-rank test was performed. Results: On quantitative evaluation, both rSI and RC ratios of all segments of the pancreaticobiliary tree at SS-FSE BH sequence were higher than those at 3D-FSE BH sequences. This finding was statistically significant (P0.60) between the two radiologists. Conclusion: The SS-FSE sequence is performed faster and significantly improves image quality; thus, it should be included into the routine MRCP sequence protocol at 3.0 T. Furthermore, we recommended SS-FSE BH MRCP examination to be applied to uncooperative patients or patients in emergency because of its short acquisition time (1 s). (c) 2013 Elsevier Inc. All rights reserved