Anatomy Learning from Prosected Cadaveric Specimens Versus Plastic Models: A Comparative Study of Upper Limb Anatomy.

Human cadaveric prosections are a traditional, effective, and highly appreciated modality of anatomy learning. Plastic models are an alternative teaching modality, though few studies examine their effectiveness in learning of upper limb musculoskeletal anatomy. The purpose of this study is to investigate which modality is associated with a better outcome, as assessed by students' performance on examinations. Overall, 60 undergraduate medical students without previous knowledge of anatomy participated in the study. Students were assigned into two groups. Group 1 attended lectures and studied from cadaveric prosections (n = 30) and Group 2 attended lectures and used plastic models in the laboratory (n = 30). A knowledge assessment, including examination with tag questions (spot test) and written multiple-choice questions, was held after the end of the study. Students' perceptions were also investigated via an anonymous questionnaire. No significant difference in students' performance was observed between the group using prosections and the group using plastic models (32.2 ± 14.7 vs 35.0 ± 14.8, respectively; P = 0.477). Similarly, no statistically significant difference was found regarding students' satisfaction from using each learning modality (P = 0.441). Plastic models may be a valuable supplementary modality in learning upper limb musculoskeletal anatomy, despite their limitations. Easy to use and with no need for maintaining facilities, they are highly appreciated by students and can be useful when preparing for the use of cadaveric specimens.

Magnetic resonance morphometry of the adult normal lumbar intervertebral space.

PURPOSE: This study aims to: (a) quantify and evaluate normal relationships between neighboring spinal units using MR imaging indices, (b) propose an easy-to-apply-and-reproduce method of estimating the correct amount of distraction when surgically restoring a collapsed intervertebral disc, based on individualized measurements. METHODS: This is a retrospective cross-sectional MR imaging study of 119 adult subjects, aged 18-54, asymptomatic for low back pain. Each of the examinees should demonstrate two or more consecutive intervertebral discs classified as Pfirrmann grade I or II to be included. We measured and studied the relationships of disc height index, Dabbs index, Farfan index, disc convexity index and mean and posterior disc height per spinal level using multiple regression analysis. All measurements were tested for intra- and interobserver agreement by two raters. RESULTS: DHI, Dabbs, Farfan, and mean disc height had a statistically significant correlation with the spinal level and age. Our results were highly reproducible, with excellent inter- and intraobserver agreement and reliability between two raters (ICC = 0.992 and 0.994, respectively). Furthermore, we expressed each intervertebral space as a percentage of its adjacent space, introducing the coefficient α factor for every intervertebral space. CONCLUSIONS: Our results suggest that a normal values' database to refer during preoperative planning of correction of a degenerated intervertebral disc is feasible. Our study offers new anatomical and radiological insight in terms of spinal measurements and their potential correlation with current surgical techniques. A new approach for calculating disc space as an expression of its adjacent disc has been introduced with various potential applications.

Anatomy learning from prosected cadaveric specimens versus three-dimensional software: A comparative study of upper limb anatomy.

INTRODUCTION: Modern, three-dimensional (3D) anatomy software is a promising teaching method, though few studies examine its effectiveness on upper limb and musculoskeletal anatomy learning. The purpose of this study is to investigate which method is associated with a better outcome, as assessed by students' performance on examinations, when comparing learning with prosections to the use of 3D software. MATERIALS AND METHODS: Two groups of undergraduate, first-year medical students without previous knowledge of anatomy were compared. Overall, 72 students attended lectures and cadaveric prosections in the laboratory (n=40), or lectures and the BioDigital Human software (n=32). Four hours of lectures and four hours of laboratory work, combining brief demonstration and independent study in small teams, were completed by each group. An anonymous examination, including tag questions from both cadaveric and 3D images, and multiple-choice questions, was held after the end of the educational process. Students' perceptions were also investigated via an anonymous questionnaire, which comprised 15 questions. Chi-square and student's t-test were used for comparisons. RESULTS: Students using the 3D software showed better performance in examinations, compared to students using prosection (mean: 55.88±19.60 vs. 48±16.11; p=0.05, Cohen's d=0.5). No statistically significant difference was found regarding students' satisfaction from using each learning method (p=0.39). CONCLUSIONS: Although prosection is the most common method of teaching anatomy, recent technologies, such as 3D software, are also considered useful teaching tools. However, further research has to be done before they can be safely used as a part of a multimodal curriculum, since results from this study are limited to the upper limb musculoskeletal anatomy.

Great trochanter bursitis vs sciatica, a diagnostic-anatomic trap: differential diagnosis and brief review of the literature.

PURPOSE: The purpose of this study is to point out the difficulty of differentiating great trochanter bursitis (GTB) from sciatica and estimating the prevalence of GTΒ, in patients poorly diagnosed with sciatica in their first visit to the general practitioner and referred to a spine infirmary. METHODS: The diagnosis of GTΒ was made based on history and physical examination, and was confirmed by ultrasonography and/or response to an anesthetic plus corticosteroid injection to the trochanteric bursa. Demographic and clinical characteristics of the study group were evaluated. The statistical analysis was held with the SPSS pc package (version 24.0). RESULTS: In a total of 657 referrals for sciatica, 72 patients (10.95%) were incorrectly diagnosed as suffering from sciatica, whereas, in fact, they were suffering from GTΒ. In addition, 18 patients (2.74%) were diagnosed as suffering from persistent sciatica with coexisting GTΒ. More women than men had GTΒ (79-11). Mean age for patients with sciatica diagnosis but suffering from GTΒ was 60 years. Mean age for patients with both sciatica and GTΒ was 61 years. CONCLUSIONS: The GTB is a common clinical entity in middle-aged women, which can escape from the physician in cases of incomplete medical history and clinical examination, leading to unnecessary imaging tests and treatment approaches, burdening both the patient and the health system. Early diagnosis of GTB may dramatically reduce cost, prevent unwanted and inappropriate imaging exams and treatment, and make the patient free of symptoms immediately. These slides can be retrieved under Electronic Supplementary Material.

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.

Computer-based automated estimation of breast vascularity and correlation with breast cancer in DCE-MRI images.

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) with gadolinium constitutes one of the most promising protocols for boosting up the sensitivity in breast cancer detection. The aim of this study was twofold: first to design an image processing methodology to estimate the vascularity of the breast region in DCE-MRI images and second to investigate whether the differences in the composition/texture and vascularity of normal, benign and malignant breasts may serve as potential indicators regarding the presence of the disease. Clinical material comprised thirty nine cases examined on a 3.0-T MRI system (SIGNA HDx; GE Healthcare). Vessel segmentation was performed using a custom made modification of the Seeded Region Growing algorithm that was designed in order to identify pixels belonging to the breast vascular network. Two families of features were extracted: first, morphological and textural features from segmented images in order to quantify the extent and the properties of the vascular network; second, textural features from the whole breast region in order to investigate whether the nature of the disease causes statistically important changes in the texture of affected breasts. Results have indicated that: (a) the texture of vessels presents statistically significant differences (p<0.001) between normal, benign and malignant cases, (b) the texture of the whole breast region for malignant and non-malignant breasts, produced statistically significant differences (p<0.001), (c) the relative ratios of the texture between the two breasts may be used for the discrimination of non-malignant from malignant patients, and (d) an area under the receiver operating characteristic curve of 0.908 (AUC) was found when features were combined in a logistic regression prediction rule according to ROC analysis.

IFNs-signaling effects on lung cancer: an up-to-date pathways-specific review.

IFNs have found important applications in clinical medicine, including the treatment of lung malignancies. The biological effect of the IFN-receptor signaling is regulated essentially by three factors: the expression profile of the IFN itself, the profile of the receptor, and the expression of target genes. IFNs initiate their signaling by binding to specific receptors. The activated IFNs can directly induce gene transcription and/or multiple downstream signaling that both induce diverse cellular responses including the cell cycle arrest and the apoptosis in tumor cells. We provided evidence that IFN-γ enhances the pro cell death effects of Fas/CD95 in human neoplastic alveolar epithelial cell line, A549. We also found that p27 protein plays a pivotal role in the inducing cell death of IFNγ-CH-11-treated A549 cells, since it is involved in the Ras/Raf signaling pathway. This article discusses recent insights into these possible additional functions of IFNs in lung cancer treatment.

Quadratus femoris tear as an unusual cause of hip pain: a case report.

PURPOSE: To show that quadratus femoris muscle partial or complete tear is an extremely rare if not underdiagnosed cause of hip pain. METHODS: We present the case of a 75-year-old Caucasian woman with spontaneous non-traumatic quadratus femoris tear. RESULTS: Computed Tomography showed quadratus femoris tear with occult underlying ischiofemoral impingement pathology. CONCLUSIONS: Quadratus femoris muscle is a hip external rotator and adductor and is situated along the posterior aspect of the hip joint and its proximity of anatomy with other external rotators leads to diagnostic pitfalls for radiologists. Identification of the exact muscle tear will establish the diagnosis, guide the proper physical therapy and reliably inform the patient what to expect after treatment.

Fast sequences MR imaging at the investigation of painful skeletal sites in patients with hip osteonecrosis.

BACKGROUND: Multiple osteonecrotic foci can be clinically silent when located in metaphyses and becomes painful when it affects juxta-articular areas. The purpose of this study was to assess the value of fast MR imaging to depict the underlying pathology in cases with skeletal pain other than the already diagnosed hip osteonecrosis. METHODS/DESIGN: Between 2008 and 2013, 49 patients with already diagnosed hip osteonecrosis reported symptoms of deep skeletal pain in an anatomical site different from the affected hip joint. All patients after thorough history & clinical examination underwent evaluation with x-rays and a single fat suppressed sequence with MR Imaging applying either T2-w TSE or STIR-TSE at the painful site. False positive and false negative findings were recorded for the conventional x-rays and compared to MRI. DISCUSSION: Forty four (89.8%) patients were positive for osteonecrotic lesions in this study and 76 symptomatic osteonecrosis lesions were revealed at 14 distinct anatomic sites. The agreement between the x-ray findings and the MR imaging regarding osteonecrosis was 46.9%. Plain x-rays showed 43.4% sensitivity, 100% specificity, 100% positive predictive value and 10.4% negative predictive value. Fast MR imaging with fat suppressed sequences is necessary and adequate as a single method for the investigation of painful skeletal sites in patients with already diagnosed hip osteonecrosis. It allows early diagnosis of the potentially debilitating multiple juxta-articular lesions and consequently their prompt management.

CNS myelin sheath is stochastically built by homotypic fusion of myelin membranes within the bounds of an oligodendrocyte process.

Myelin - the multilayer membrane that envelops axons - is a facilitator of rapid nerve conduction. Oligodendrocytes form CNS myelin; the prevailing hypothesis being that they do it by extending a process that circumnavigates the axon. It is pertinent to ask how myelin is built because oligodendrocyte plasma membrane and myelin are compositionally different. To this end, we examined oligodendrocyte cultures and embryonic avian optic nerves by electron microscopy, immuno-electron microscopy and three-dimensional electron tomography. The results support three novel concepts. Myelin membranes are synthesized as tubules and packaged into "myelinophore organelles" in the oligodendrocyte perikaryon. Myelin membranes are matured in and transported by myelinophore organelles within an oligodendrocyte process. The myelin sheath is generated by myelin membrane fusion inside an oligodendrocyte process. These findings abrogate the dogma of myelin resulting from a wrapping motion of an oligodendrocyte process and open up new avenues in the quest for understanding myelination in health and disease.

Comparison of PD BLADE with fat saturation (FS), PD FS and T2 3D DESS with water excitation (WE) in detecting articular knee cartilage defects.

The purpose of this study, is to compare the sequences: 1) proton density (PD) BLADE (BLADE is a PROPELLER-equivalent implementation of the Siemens Medical System) with fat saturation (FS) coronal (COR), 2) PD FS COR, 3) multi-planar reconstruction (MPR) with 3mm slice thickness and 4) multi-planar reconstruction (MPR) with 1.5mm slice thickness, both from the T2 3D-double-echo steady state (DESS) with water excitation (WE) sagittal (SAG), regarding their abilities to identify changes in the femorotibial condyle cartilage in knee MRI examinations. Thirty three consecutive patients with osteoarthritis (18 females, 15 males; mean age 56years, range 37-71years), who had been routinely scanned for knee examination using the previously mentioned image acquisition techniques, participated in the study. A quantitative analysis was performed based on the relative contrast (ReCON) measurements, which were taken both on normal tissues as well as on pathologies. Additionally, a qualitative analysis was performed by two radiologists. Motion and pulsatile flow artifacts were evaluated. The PD BLADE FS COR sequence produced images of higher contrast between Menisci and Cartilage, Fluid and Cartilage, Pathologies and Cartilage as well as of the Conspicuousness Superficial Cartilage and it was found to be superior to the other sequences (p<0.001). The sequences T2 3D DESS 1.5mm and T2 3D DESS 3mm were significantly superior to the PD BLADE FS COR and the PD FS COR sequences in the visualization of Bone and Cartilage and the Conspicuousness Deep Surface Cartilage. This pattern of results is also confirmed by the quantitative analysis. PD FS BLADE sequences are ideal for the depiction of the cartilage pathologies compared to the conventional PD FS and T2 3D DESS sequences.

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 (P<.01). On qualitative evaluation, the two radiologists found intrahepatic ducts and pancreatic ducts to be better visualized with SS-FSE BH than with 3D-FSE BH sequence. This finding was statistically significant (P<.02). One of them found extrahepatic ducts to be significantly better visualized with SS-FSE BH sequence. Moreover, the frequency of artifacts was lower in the SS-FSE sequence, a finding that was of statistical significance. Interobserver agreement analysis found at least substantial agreement (κ>0.60) 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).

Application value of 3T ¹H-magnetic resonance spectroscopy in diagnosing breast tumors.

BACKGROUND: Assessment of breast lesions with magnetic resonance imaging (MRI) provides a means for lesion detection and diagnosis. Proton (hydrogen-1) magnetic resonance spectroscopy ((1)H-MRS) has been proposed as a useful diagnostic technique in providing metabolic information of suspicious breast lesions. PURPOSE: To determine the clinical significance of in-vivo single voxel (1)H-MRS at 3T in the assessment of benign and malignant breast lesions in combination with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MATERIAL AND METHODS: Twenty-four women with known breast abnormalities from conventional imaging (mammography, ultrasonography) underwent DCE-MRI at a 3T MR scanner and 26 breast lesions were detected. Breast lesions were assessed according BI-RADS classification. Single voxel (1)H-MRS was performed after gadolinium administration and choline peak was qualitatively evaluated. All lesions were confirmed histologically from the surgically excised specimens. Sensitivity, specificity, and accuracy of the (1)H-MRS, of the BI-RADS classification and of their combination (DCE-MRI + (1)H-MRS) were calculated. RESULTS: Fifteen out of 26 lesions proved to be malignant and 11 proved to be benign. In our study (1)H-MRS showed sensitivity 80%, specificity 81.8%, and accuracy 80.7%. DCE-MRI showed sensitivity 100%, specificity 63.6%, and accuracy 84.6%. The combination of DCE-MRI and (1)H-MRS provided higher accuracy (96.4%), as well as higher specificity 81.8% compared to BI-RADS classification. CONCLUSION: The combined use of (1)H-MRS and DCE-MRI found to have improved diagnostic performance in the assessment of equivocal breast lesions. (1)H-MRS can be used as a useful adjunct during lesion characterization in clinical routine in cases classified as BI-RADS 3 and 4.

A method for limiting pitfalls in the production of enhancement kinetic curves in 3T dynamic magnetic resonance mammography.

PURPOSE: The aim of the present study is to investigate means for the reduction or even elimination of enhancement kinetic curve errors due to breast motion in order to avoid pitfalls and to increase the sensitivity and specificity of the method. METHODS: 115 women underwent breast Magnetic Resonance Imaging (MRI). All patients were properly immobilized in a dedicated bilateral phased array coil. A magnetic resonance unit 3-Tesla (Signa, GE Healthcare) was used. The following sequences were applied: (I) axial Τ2-TSE, (II) axial STIR and (III) Vibrant axial T1-weighted fat saturation (six phases). Kinetic curves were derived semi-automatically using the software of the system and manually by positioning the regions of interest (ROI) from stable reference points in all the phases. RESULTS: 376 abnormalities in 115 patients were investigated. In 81 (21.5%) cases, a change of the enhancement kinetic curve type was found when the two different methods were used. In cases of large fatty breasts, a change of the enhancement kinetic curve type in 13 lesions was found. In cases of small and dense breasts, only in 4 lesions the kinetic curve type changed, whereas in cases of small and fatty breasts, the kinetic curve type changed in 64 lesions (50 were observed in left breasts and 14 in right breasts). CONCLUSIONS: The derivation of enhancement kinetic curves should be performed by controlling and verifying that the ROIs lay at the same location of the lesion in all the phases of the dynamic study.

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.

Characterization of breast lesions with CE-MR multimodal morphological and kinetic analysis: comparison with conventional mammography and high-resolution ultrasound.

OBJECTIVE: Evaluation of the diagnostic value of magnetic resonance mammography and comparison with conventional mammography and ultrasonography in cases of women with suspicious breast lesions. SUBJECTS AND METHODS: Sixty-nine women (age range 39-68 years) with 78 focal breast lesions were examined with mammography, ultrasonography and dynamic magnetic resonance mammography. The lesions were classified according to the Breast Imaging Reporting and Data System (BI-RADS) lexicon of the American College of Radiology for each diagnostic method. Histological reports were available after biopsy or surgical excision of the lesions. RESULTS: Pathological examination confirmed that 53 lesions were malignant and 25 benign. Conventional mammography estimated a total of 59/78 lesions as malignant with 44 true positive lesions, ultrasonography estimated a total of 50/78 lesions as malignant with 44 true positive lesions and magnetic resonance mammography estimated a total of 66/78 lesions as malignant with 52 true positive lesions. Sensitivity and specificity of magnetic resonance mammography in the diagnosis of malignancy was 98.1% and 44%, of conventional mammography 83% and 40% and of ultrasonography 83% and 76%. Negative predictive value for magnetic resonance mammography was 91.7%, for ultrasonography 67.9% and for mammography 52.6% for malignancies. CONCLUSION: Magnetic resonance mammography has the highest negative predictive value compared with mammography and ultrasound in cases of suspicious breast lesions. The combination of morphologic and enhancement criteria can improve the diagnostic capability of magnetic resonance mammography (MRM) in breast lesion characterization.

Nuclear localization of cytokeratin 8 and the O-linked N-acetylglucosamine-containing epitope H in epithelial cells of infiltrating ductal breast carcinomas: a combination of immunogold and EDTA regressive staining methods.

In a previous study, the authors have shown cytokeratin 8 (CK8) and epitope H ultrastructural localization in breast cancer cell nuclei. Epitope H contains an O-linked N-acetylglucosamine (O-GlcNAc) residue in a specific conformation and/or environment recognized by monoclonal antibody H. In this study, double immunogold labeling of CK8 and epitope H combined with the EDTA regressive staining method was applied in biopsy material from infiltrating ductal breast carcinomas and fibroadenomas, to localize both antigens in correlation to RNPs distribution in the nuclear subcompartments of cancer cells. CK8 and epitope H were localized mostly over condensed chromatin, whereas staining was weaker over interchromatin granule clusters and perichromatin fibers. These results revealed, the distribution of CK8 in the nucleus as MAR-binding protein, contributing in the organization of the nuclear DNA in the neoplastic cell, as well as the distribution of O-GlcNAc glycosylated polypeptides bearing the epitope H. The latter finding indicates that these polypeptides might play a significant role in the neoplastic behavior of breast cancer cells because they colocalize in the same nuclear subcompartments with proteins modified by O-GlcNAc, such as hnRNPs G and A1, RNA polymerase II, its transcription factors, and the oncogene product of c-myc. These proteins are known to participate in coordinated transcription/RNA processing events, contributing in the neoplastic behavior of breast cancer cells.

Expression of heregulin in human coronary atherosclerotic lesions.

BACKGROUND: Endothelial cells, monocytes/macrophages, and vascular smooth muscle cells contribute to the establishment and progression of atherosclerotic lesions by expressing growth and inflammatory factors. The aim of the present study was to determine whether heregulin (HRG) is associated with human coronary artery disease. METHODS: Twenty-six fresh human coronary artery segments were collected at autopsy. Expression of cysteine-rich 61 (CYR61) and VEGF in response to HRG was studied in the human endothelial cell line EA.hy926, and expression of CYR61 and HRG was evaluated in activated macrophages isolated from peripheral blood of healthy donors. RESULTS: We found that HRG was overexpressed at the protein and mRNA level in all lesions analyzed and gradually increased as the stages of the lesions progressed. Expression of HRG was observed in the intima primarily in macrophages. The same specimens were analyzed for the expression of CYR61, an angiogenetic factor regulated by HRG in breast cancer epithelial cells. CYR61 was expressed in both normal and atheromatic specimens, but its expression was significantly enhanced in macrophages of the intima. Activation of primary human macrophages results in increased expression of both HRG and CYR61. In addition, studies in endothelial cells where no endogenous HRG is present showed that HRG induces expression of CYR61 and secretion of VEGF. CONCLUSIONS: HRG may, therefore, play an important role in the development of coronary artery disease and the expansion of the atherosclerotic plaque and may locally regulate the expression of the angiogenetic factor CYR61.

Mitochondria-rich normal, metaplastic, and neoplastic cells show overexpression of the epitope H recognized by the monoclonal antibody H.

The epitope H contains an O-linked N-acetylglucosamine (O-GlcNAc) residue in a specific conformation and/or environment recognized by monoclonal antibody H (mAbH). We have previously shown that the epitope H is present in more than one polypeptide and in various types of normal and pathological cells. In the present study, we focused on mitochondria-rich normal, metaplastic, and neoplastic cells, prompted by our recent immuno-electron microscopy findings that mAbH clearly stains the mitochondria of breast epithelial cells in infiltrating ductal breast carcinomas and fibroadenomas. The indirect immunoperoxidase method was applied using the mAbH to investigate the distribution of the epitope H in mitochondria-rich normal cells and in metaplastic and neoplastic oncocytic cells. Immunohistochemical staining for the mAbH was observed in oxyphil cells of parathyroid glands, in striated duct cells of parotid glands, in urinary tubules of kidneys, in parietal cells of gastric body mucosa, in oxyphil cells of Hashimoto's thyroiditis, in epithelial cells of Warthin's tumors of the parotid gland, in neoplastic cells of oxyphil adenomas and carcinomas (Hürthle's tumors) of the thyroid gland, and in neoplastic cells of oncocytomas of the kidneys. The present study shows that the epitope H is strongly expressed in mitochondria-rich normal cells, as well as in metaplastic and neoplastic oncocytic cells, which are known to have cytoplasms packed with mitochondria. Since mAbH recognizes an O-GlcNAc residue, our findings indicate that O-GlcNAc-glycosylated polypeptides are present at mitochondria where the components of the respiratory chain and energy transduction are localized. These findings may be of interest for gaining insight into the histophysiology of mitochondria-rich normal cells and into the pathogenesis of oncocytic lesions, since O-GlcNAc glycosylation may modify proteins involved in oncogenesis such as tumor suppressor proteins and oncoproteins, as well as proteins with important biological functions such as cytoskeletal proteins, transcription factors, heat-shock proteins, and chromatin proteins.