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

STUDY DESIGN: Human herniated discs were obtained from discectomy specimens for the immunohistochemical detection of O-GlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT). PURPOSE: This study aimed to quantify the extent of O-GlcNAcylation and its associated enzymes (OGT/OGA) in human degenerated intervertebral discs. OVERVIEW OF LITERATURE: The 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. METHODS: Fifty-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. RESULTS: We 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. CONCLUSIONS: O-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.