Periphery Of Nodules Research Articles

Differentiation of benign from malignant thyroid nodules with acoustic radiation force impulse technique

The aim of our study was to assess the performance of acoustic radiation force impulse (ARFI) imaging to differentiate benign from malignant thyroid nodules. 182 patients who needed thyroid surgery were examined. All patients and 50 healthy volunteers underwent ARFI sonoelastography, which quantitatively analysed the elasticity and hardness of the nodule's centre and periphery. ARFI values showed a statistical significance between malignant nodules and benign nodules and common thyroid parenchyma, in both the centre and periphery of nodules (p < 0.01). There was no significant difference between benign nodules and common thyroid parenchyma in either the nodule's centre or periphery (p > 0.05). There was no significant difference between the nodule's centre and periphery of the elastic parameters in both the benign and malignant nodules. There was a statistically significant difference among the two areas (the central group and the peripheral group) under the receiver operating characteristic curve, and the optimal model was the peripheral group. For differentiation of malignant from benign nodules, the sensitivity and specificity were 96.3% and 96.2%, respectively, when 2.545 m s(-1) was chosen as a cut-off value in the peripheral group. ARFI imaging may be helpful to differentiate benign nodules from malignant thyroid nodules. The selecting measurement position is important in ARFI imaging, and it has good diagnostic value in clinical applications. This study shows the diagnostic contribution of ARFI imaging in thyroid lesions.

Dupuytren’s disease

Dupuytren’s disease is a chronic inflammatory process which produces contractures of the fingers. The nodules present in Dupuytren’s tissue contain inflammatory cells, mainly lymphocytes and macrophages. These express a common integrin known as VLA4. The corresponding binding ligands to VLA4 are vascular cell adhesion molecule-1 (VCAM-1) present on the endothelial cells and the CS1 sequence of the fibronectin present in the extracellular matrix. Transforming growth factor-beta (TGF-ß) is a peptide hormone which has a crucial role in the process of fibrosis. We studied tissue from 20 patients with Dupuytren’s disease, four samples of normal palmar fascia from patients undergoing carpal tunnel decompression and tissue from ten patients who had received perinodular injections of depomedrone into the palm five days before operation. The distribution of VLA4, VCAM-1, CS1 fibronectin and TGF-ß was shown by immunohistochemistry using an alkaline phosphorylase method for light microscopy. In untreated Dupuytren’s tissue CS1 fibronectin stained positively around the endothelial cells of blood vessels and also around the surrounding myofibroblasts, principally at the periphery of many of the active areas of the Dupuytren’s nodule. VCAM-1 stained very positively for the endothelial cells of blood vessels surrounding and penetrating the areas of high nodular activity. VCAM-1 was more rarely expressed outside the blood vessels. VLA4 was expressed by inflammatory cells principally in and around the blood vessels expressing VCAM-1 and CS1 but also on some cells spreading into the nodule. TGF-ß stained positively around the inflammatory cells principally at the perivascular periphery of nodules. These cells often showed VLA4 expression and co-localised with areas of strong production of CS1 fibronectin. Normal palmar fascia contained only scanty amounts of CS1 fibronectin, almost no VCAM-1 and only an occasional cell staining positively for VLA4 or TGF-ß. In the steroid-treated group, VCAM-1 expression was downregulated in the endothelium of perinodular blood vessels and only occasional inflammatory cell expression remained. Expression of CS1 fibronectin was also much reduced but still occurred in the blood vessels and around the myofibroblast stroma. VLA4-expressing cells were also reduced in numbers. A similar but reduced distribution of production of TGF-ß was also noted. Our findings show that adherence of inflammatory cells to the endothelial wall and the extravasation into the periphery of the nodule may be affected by steroids, which reduce expression of VCAM-1 in vivo. This indicates that therapeutic intervention to prevent the recommencement of the chronic inflammatory process and subsequent fibrosis necessitating further surgery may be possible.

Dupuytren's disease. A model for the mechanism of fibrosis and its modulation by steroids.

Dupuytren's disease is a chronic inflammatory process which produces contractures of the fingers. The nodules present in Dupuytren's tissue contain inflammatory cells, mainly lymphocytes and macrophages. These express a common integrin known as VLA4. The corresponding binding ligands to VLA4 are vascular cell adhesion molecule-1 (VCAM-1) present on the endothelial cells and the CS1 sequence of the fibronectin present in the extracellular matrix. Transforming growth factor-beta (TGF-beta) is a peptide hormone which has a crucial role in the process of fibrosis. We studied tissue from 20 patients with Dupuytren's disease, four samples of normal palmar fascia from patients undergoing carpal tunnel decompression and tissue from ten patients who had received perinodular injections of depomedrone into the palm five days before operation. The distribution of VLA4, VCAM-1, CS1 fibronectin and TGF-beta was shown by immunohistochemistry using an alkaline phosphorylase method for light microscopy. In untreated Dupuytren's tissue CS1 fibronectin stained positively around the endothelial cells of blood vessels and also around the surrounding myofibroblasts, principally at the periphery of many of the active areas of the Dupuytren's nodule. VCAM-1 stained very positively for the endothelial cells of blood vessels surrounding and penetrating the areas of high nodular activity. VCAM-1 was more rarely expressed outside the blood vessels. VLA4 was expressed by inflammatory cells principally in and around the blood vessels expressing VCAM-1 and CS1 but also on some cells spreading into the nodule. TGF-beta stained positively around the inflammatory cells principally at the perivascular periphery of nodules. These cells often showed VLA4 expression and co-localised with areas of strong production of CS1 fibronectin. Normal palmar fascia contained only scanty amounts of CS1 fibronectin, almost no VCAM-1 and only an occasional cell staining positively for VLA4 or TGF-beta. In the steroid-treated group, VCAM-1 expression was downregulated in the endothelium of perinodular blood vessels and only occasional inflammatory cell expression remained. Expression of CS1 fibronectin was also much reduced but still occurred in the blood vessels and around the myofibroblast stroma. VLA4-expressing cells were also reduced in numbers. A similar but reduced distribution of production of TGF-beta was also noted. Our findings show that adherence of inflammatory cells to the endothelial wall and the extravasation into the periphery of the nodule may be affected by steroids, which reduce expression of VCAM-1 in vivo. This indicates that therapeutic intervention to prevent the recommencement of the chronic inflammatory process and subsequent fibrosis necessitating further surgery may be possible.

Expression of osteopontin in Meckel's cartilage cells during phenotypic transdifferentiation in vitro, as detected by in situ hybridization and immunocytochemical analysis.

The localization of osteopontin (OP) was examined in Meckel's cartilage cells that bipotentially expressed cartilage and bone phenotypes during cellular transformation in vitro. Cultured cells were analyzed by in situ hybridization, immunostaining followed by light and electron microscopy, electron microscopy, and electron probe microanalysis. The combination of ultrastructural analysis and immunoperoxidase staining indicated that OP-synthesizing cells were cells that were autonomously undergoing a change from chondrocytes to bone-forming cells at the top of nodules. Double immunofluorescence staining of 2-week-old cultures revealed that OP was first synthesized by chondrocytic cells at the top of nodules. After further time in culture, the distribution of OP expanded from the central toward the peripheral regions of the nodules. Electron probe microanalysis revealed that the localization of OP was associated with matrices of calcified cartilage and osteoid nodules that contained calcium and phosphorus. Immunoperoxidase electron microscopy revealed that, in addition to the intracellular immunoreactivity in chondrocytes and small round cells that were undergoing transformation, matrix foci of calcospherites and matrix vesicles, in particular, included growing crystals that were immunopositive for OP. An intense signal due to mRNA for OP in 3-week-old cultures was detected in nodule-forming round cells, while fibroblastic cells, spreading in a monolayer over the periphery of nodules, were only weakly labeled. These findings indicate that OP might be expressed sequentially by chondrocytes and by cells that are transdifferentiating further and exhibit an osteocytic phenotype, and moreover, that expression of OP is closely associated with calcifying foci in the extracellular matrix.

Autoradiographic Evaluation of Monoclonal Antibodies Access to Melanoma-Associated Antigens in Melanoma Xenografts

Autoradiography of nude mice bearing human malignant melanoma xenografts was performed to characterize the distribution pattern of radioiodinated anti-melanoma monoclonal antibodies (MoAb) and fragments in macroscopic tumor nodules. Non-uniformity of radioactivity distribution was seen in all MoAb-xenograft combinations. The predominant patterns were marked deposition of radioactivity either in the periphery of nodules or in sharply delimited intra-tumoral foci. These patterns were generated by limitations in the accessibility of melanoma tissue rather than gross necrosis or heterogeneity of antigen expression. Computer-aided densitometry of autoradiograms was used to elaborate the difference of accumulation in intra-tumoral hot spots versus cold areas. It was found that increasing uniformity was achieved by increasing the dose of MoAb (i.e., intact IgG) injected, whereas a reduction in the size of MoAb (IgG greater than F(ab')2 greater than Fab) showed no such effect.

Nodulin Gene Expression and ENOD2 Localization in Effective, Nitrogen-Fixing and Ineffective, Bacteria-Free Nodules of Alfalfa.

Alfalfa plants form bacteria-free nodules in response to a number of agents, including Rhizobium meliloti exo mutants, Agrobacterium tumefaciens transconjugants carrying cloned R. meliloti nodulation genes, and compounds that function as auxin transport inhibitors, N-( 1-naphthyl)phthalamic acid or 2,3,5-triiodobenzoic acid. These bacteria-free nodules contain transcripts for the nodulins Nms30 and MsENOD2; transcripts for late nodulins like leghemoglobin are not detected. In situ hybridization studies demonstrated that ENOD2 transcripts were localized in parenchyma cells at the base and along the periphery of nitrogen-fixing alfalfa root nodules. The ENOD2 gene was also expressed in a tissue-specific manner in nodules elicited by N-( 1-naphthyl)phthalamic acid and 2,3,5-triiodobenzoic acid. In bacteria-free nodules induced by R. meliloti exo mutants and A. tumefaciens transconjugants carrying either one or both R. meliloti symbiotic plasmids, ENOD2 transcripts were also detected but were usually localized to parenchyma cells at the base instead of along the periphery of the nodule. On the basis of the pattern of ENOD2 gene expression, we conclude that the developmental pathway of bacteria-free nodules, whether bacterially or chemically induced, is the same as that of nitrogen-fixing nodules, and, furthermore, that the auxin transport inhibitors in their action mimic some factor(s) that trigger nodule development.