Pathological Migration Research Articles

Biological properties of cardiac stem cells in normal and pathological conditions - matrix makes a difference

Cardiac cells and extracellular matrix (ECM) are reciprocally related and their characteristics are modified in response to developmental or pathophysiological cues. Adult human cardiac tissue regeneration mediated by cardiac stem cells (CSCs) is strictly regulated and, hypothetically, impaired by the ECM-CSC signalling in the pathological conditions. To test this hypothesis, we isolated cardiac fibroblasts (CFs) and CSCs from the atria of age-matched adult human normal (n=9) and pathological hearts (ischemic cardiomyopathy, n=11). The CFs were cultured in order to obtain ECM coating and conditioned medium, which were characterized by immunoblotting and ELISA, respectively. Next, we examined the effects of CF-derived ECM and CF-conditioned medium on normal and pathological CSC proliferation, apoptosis, and migration in vitro. The ECM produced by CFs from normal heart was composed mainly of fibronectin, laminin α2 and collagen I, while that produced by CFs from hearts with ischemic cardiomyopathy contained also laminin α1 and tenascin X. Compared to the normal CF-conditioned medium, that conditioned by pathological CFs contained twice as much IGF1 and HGF, and it stimulated proliferation and migration, while reducing apoptosis of CSCs. In the presence of pathological CF-derived ECM, there was a nearly 2-fold increase (p<0.05) in proliferation of normal and pathological CSCs, when compared to normal CF-derived ECM. Moreover, pathological CF-derived ECM reduced CSC apoptosis, specifically in cells from pathological heart. However, in the same conditions, the migration of pathological CSCs was significantly lower. These results indicate that the activity of CFs and its modification in chronic ischemic conditions determines biological properties of CSCs. Such an influence should be taken into consideration when attempting ischemic cardiac tissue stem cell-based regeneration.

Tetraspan TM4SF5-dependent direct activation of FAK and metastatic potential of hepatocarcinoma cells

Transmembrane 4 L six family member 5 (TM4SF5) plays an important role in cell migration, and focal adhesion kinase (FAK) activity is essential for homeostatic and pathological migration of adherent cells. However, it is unclear how TM4SF5 signaling mediates the activation of cellular migration machinery, and how FAK is activated during cell adhesion. Here, we showed that direct and adhesion-dependent binding of TM4SF5 to FAK causes a structural alteration that may release the inhibitory intramolecular interaction in FAK. In turn, this may activate FAK at the cell's leading edge, to promote migration/invasion and in vivo metastasis. TM4SF5-mediated FAK activation occurred during integrin-mediated cell adhesion. TM4SF5 was localized at the leading edge of the cells, together with FAK and actin-organizing molecules, indicating a signaling link between TM4SF5/FAK and actin reorganization machinery. Impaired interactions between TM4SF5 and FAK resulted in an attenuated FAK phosphorylation (the signaling link to actin organization machinery) and the metastatic potential. Our findings demonstrate that TM4SF5 directly binds to and activates FAK in an adhesion-dependent manner, to regulate cell migration and invasion, suggesting that TM4SF5 is a promising target in the treatment of metastatic cancer.

Recurrence of posterior polymorphous corneal dystrophy is caused by the overgrowth of the original diseased host endothelium

Posterior polymorphous corneal dystrophy (PPCD) is a rare, bilateral autosomal dominant disorder affecting primarily the corneal endothelium and descemet membrane (DM). The aim of this study was to establish the origin of abnormal endothelium in a patient with PPCD exhibiting cornea graft failure after keratoplasty surgery. A sex-mismatched graft obtained from a patient with PPCD who underwent repeat penetrating keratoplasty and the patient's original cornea were investigated. Combined fluorescent immunohistochemistry for cytokeratin (CK) 19 (a marker of aberrant PPCD endothelium) with fluorescence in situ hybridization (FISH) of the sex chromosomes were used in order to characterize the cells on the posterior graft surface. The pathological endothelium of the failed PPCD cornea revealed strong positivity for CK19 using fluorescent immunohistochemistry. In all the CK19-positive cells, both X and Y chromosomes were simultaneously detected using FISH. The results clearly showed the original cells of the patient (XY), within 3.5years, almost totally overgrown the posterior corneal surface of the graft (XX). Moreover, an abnormal posterior collagenous layer populated by fibroblast-like cells was observed between DM and the endothelium in the failed graft, but its exact origin could not be established due to the low number of cells. Simultaneous detection of CK19 using fluorescent immunohistochemistry together with the detection of gonosomes using FISH was performed for the first time in the cornea and allowed us to prove that the recurrence of PPCD was caused by pathological abnormal proliferation and migration of recipient cells into donor graft.

Ortho-perio integrated approach in periodontally compromised patients

It is an undisputed fact that sound and strong periodontal health is a must in patients seeking orthodontic treatment. Does this mean that we are going to deny orthodontic treatment for those adults whose number is rising, more often secondary to periodontal deterioration and pathological migration of teeth resulting in aesthetic and functional problems? Need of the hour is to have an integrated approach where in periodontal treatment precedes orthodontic treatment to restore periodontal health. Orthodontic treatment should be performed under strict plaque control measures to place the teeth in a structurally balanced and functionally efficient position. Aim of this article is to familiarize the practicing clinicians both in the field of orthodontics and periodontics with current thoughts and successful clinical techniques used in the field of periodontology to regenerate lost periodontal structures. Furthermore, it aims to integrate such techniques into the orthodontic treatment of patients with severe bone loss.

Rapports réciproques entre orthodontie et parodontologie. Intérêt d'une synergie d'action effective

The aim of this article is to review evidence on the reciprocal relationships between orthodontics and periodontics. Normal intra-arch and inter-arch relationships have long been considered as an anatomic prerequisite for the preservation of dental health and function. Certain malocclusion traits are associated with difficulties in maintaining good oral hygiene and as a consequence to poor periodontal condition. Therefore, proper alignment of the teeth provided by orthodontic treatment may promote good control of soft deposit and calculus and subsequent periodontal inflammation. The tendency of orthodontic appliances, particularly the brackets and bands to promote the accumulation of plaque and thus increasing the risk of developing localized periodontal disease must however be constantly emphasized. Periodontitis involves progressive loss of the alveolar bone around the teeth, pathological tooth migration and gingival recession with pathological tooth migration and gingival recession as a possible outcome. The effectiveness of orthodontics in conjunction with periodontics in the management of these esthetic and functional defects is highlighted in this review.

Combined periodontal and orthodontic treatment of pathologic migration of anterior teeth

There is an ever increasing concern for dentofacial esthetics in adult population. The primary motivating factor for seeking orthodontic treatment is dental appearance [1]. Pathologic migration of anterior teeth is a common cause of esthetic concern among adults. Pathologic migration is defined as change in tooth position resulting from disruption of the forces that maintain teeth in normal position in relation to their arch. The disruption of equilibrium in tooth position may be caused by several etiologic factors. These include periodontal attachment loss, pressure from inflamed tissues, occlusal factors, oral habits such as tongue thrusting and bruxism, loss of teeth without replacement, gingival enlargement and iatrogenic factors. However, according to the literature, destruction of tooth supporting structures is the most relevant factor associated with pathologic migration. Periodontal disease in the upper anterior region can be in isolation or may affect more teeth. The periodontal disease and its sequale such as diastema, pathological migration, labial tipping or missing teeth often lead to functional and esthetic problems either alone or with restorative problems [2]. Advanced periodontal disease is characterized by severe attachment loss, reduced alveolar bone support, tooth mobility and gingival recession. Orthodontic treatment is initiated only after periodontal disease is brought under control [3]. This communication highlights good treatment outcome achieved in a patient with impaired dentofacial aesthetics and advanced periodontal disease.

Chemokines and their receptors as potential targets for the treatment of asthma

Asthma is a chronic and sometimes fatal disease, which affects people of all ages throughout the world. Important hallmarks of asthma are airway inflammation and remodelling, with associated bronchial hyperresponsiveness and variable airflow obstruction. These features are orchestrated by cells of both the innate (eosinophils, neutrophils and mast cells) and the adaptive (T(H)2 T cells) immune system, in concert with structural airway cells. Chemokines are important for the recruitment of both immune and structural cells to the lung, and also for their microlocalisation within the lung tissue. Specific blockade of the responses elicited by chemokines and chemokine receptors responsible for the pathological migration of airway cells could therefore be of great therapeutic interest for the treatment of asthma.

722: Pathological Characteristics and Stage Migration of Patients with Prostate Cancer and Lymph Node Invasion Undergoing an Extended Pelvic Lymph Node Dissection at a Single Institution Over a 15 Year Period

722: Pathological Characteristics and Stage Migration of Patients with Prostate Cancer and Lymph Node Invasion Undergoing an Extended Pelvic Lymph Node Dissection at a Single Institution Over a 15 Year Period

Role of fetal ultrasound and magnetic resonance imaging in the prenatal diagnosis of migration disorders

To evaluate the contribution and limitations of fetal ultrasonography (US) and magnetic resonance imaging (MRI) for the diagnosis and management of migration disorders. Over a 5-year period, 14 fetuses with pathological migration disorders, without an infectious context, were taken care of in our centre. All underwent US; nine underwent MRI as well. Sonographic and MRI data were compared with neuropathological data. The diagnosis of gyral disorders was obtained by US in 1/14 cases; other cerebral abnormalities were found suggesting neuronal disorder in the remainder. Cerebral MRI suggested gyral abnormality in eight of the nine cases. US performance is increasing. MRI appears to be a promising method for the diagnosis of fetal migration disorders, giving better results than US. It may be recommended in cases of abnormal cerebral US findings or familial clinical history. However, interpretation of MRI can be tricky and the resulting diagnosis occurs late within the pregnancy.

Myosin regulation in the migration of tumor cells and leukocytes within a three-dimensional collagen matrix

The migration of cells is a complex regulatory process which results in the generation of motor forces through the reorganization of the cytoskeleton. Here we present a comparative study of the expression and involvement of myosin in the regulation of the physiological migration of leukocytes and the pathological migration of tumor cells. We show that the involvement of myosin in the migration is distinct in these two cell types. In leukocytes, the activity of non-muscle myosin II is essential for both the spontaneous (matrix-induced) migration and the migration induced by ligands to G protein-coupled receptors, i.e. chemokines and neurotransmitters. In contrast, spontaneous tumor cell migration is largely independent of non-muscle myosin II activity, whereas the norepinephrine-induced migration is completely inhibited by either direct inhibition of non-muscle myosin II or of the kinases phosphorylating the myosin light chain, namely ROCK or the calcium/calmodulin-dependent myosin light-chain kinase.

Colorectal cancer diagnosis by a direct leukocyte migration test using a panel of tumour extracts

In a direct leukocyte migration test, peripheral blood leukocytes were pulsed with a high dose (2.5 and 0.5 mg/ml) of 3 M KCl extracts from 5 different colorectal tumours as well as with one 3 M KCl extract of normal colonic mucosa. Patients showing a pathological migration index (⩽0.80 and ⩾1.17), with 3 or more out of 5 tumour extracts, were considered as “positives”.

A modified leucocyte migration assay as indicator of malignant and non-malignant gastric mucosal alteration.

When gastric cancer patients' leucocytes were exposed to a panel of tumour extracts, leucocyte migration reactivity was "positive" before operation (90% of cases), it declined after surgery and it reappeared in patients with local recurrence or metastases. In patients with non-malignant gastric diseases, "positive" reactivity against tumour extracts was associated almost exclusively with atrophic gastritis with and without intestinal metaplasia (24/43 cases). "Positive" patients also showed a pathological migration index with an extract of normal gastric mucosa.

実験的外傷性咬合による歯周組織の変化に関するX線学的研究

The purpose of this investigation was to observe radiographically the periodontal tissue changes caused by occlusal trauma and to recognize the factors related to film viewing in diagnosis.Full cast crowns were designed on the fourth mandibular premolar in adult dogs, in order to produce injurious forces from three directions: distal, buccal and longitudinal occlusal forces.As a preliminary to this study, the most effective exposure factors for the periodontal tissue changes were determined.The standardized serial radiographs were taken at the same experimental site during 0-120 days period after cementing the full crown, and individual photograms were analyzed by the indirect radiographic image magnification and the microphotography as well as clinical observation.Results1. The most effective exposure factors to observe the periodontal tissue changes were as follows: 50 kilovoltage peak in case 15 milliamperage and 2 second exposure.2. The error seen in the standardized radiographic images was 0.6%.3. Clinical changes attributed to occlusal trauma include accumlation of dental plaque, redness and swelling of the gingiva, gingival bleeding and tooth mobility. The depth of the periodontal pocket was also increased.4. The direction of pathological migration depends upon the one of occlusal trauma.5. Radiographic changes of the periodontal tissue were as follows:increase or decrease of the width of the periodontal space, thickening or disappearance of the lamina dura, condensation or radiolucense of the bone trabeculae, and root resorption. Especially, observed in all cases, widening of the periodontal space is good objective to diagnose a occlusal trauma.6. It took about 7 to 20 days untill these radiographic evidences appear.7. The radiographic changes caused by traumatic occlusion flom three directions were characteristic respectively.The most common sites were mesio-distal cervical portion and furcation area.As above mentioned, the standardized radiographs with the most effective factors are necessary for the observation of the injurious effect upon the periodontal tissue.In addition, analysis of these radiagrams by the indirect radiographic image magnification and the microphotography is very effective.