Prevalence of ankylosing spondylitis in Spain: EPISER2016 Study.

Objective: The aim of this study was to estimate the prevalence of ankylosing spondylitis (AS) in Spain.Method: This is a cross-sectional, population-based study of people aged 20 years or older in Spain. Randomly selected individuals were contacted by telephone and rheumatic disease screening was performed. If the first screening was positive, medical records were then reviewed and/or a telephone questionnaire was conducted by a rheumatologist, followed by an appointment if necessary. Cases had to fulfil the modified New York (mNY) criteria.Results: In total, 4916 individuals were included, of whom 355 had a positive screening result for AS. Of these, 11 were classified as AS. An additional individual who reported a prior diagnosis of rheumatoid arthritis had a diagnosis of AS confirmed on review of the medical records. Estimated prevalence was 0.26% (95% CI 0.14-0.49).Conclusion: EPISER2016 is the first population-based study to estimate the prevalence of AS in Spain, which has been estimated as being similar to that in other European countries.

Systemic blockade of TNF-α does not improve insulin resistance in humans.

The purpose of this study was to determine whether long-term modulation of inflammatory activity by tumor necrosis factor (TNF)-α inhibitors has some influence on insulin resistance (IR). 16 active rheumatoid arthritis (RA) patients without CV risk factors treated with anti-TNF-α agents were included in this study. RA activity by disease activity score 28, IR by HOMA2-IR, body composition by impedance analysis, physical activity by accelerometry, abdominal fat distribution by magnetic resonance imaging, and serum level of key adipokines by ELISA were measured at baseline and during a 1-year follow-up period. Patient body mass index increased significantly (26.94 ± 3.88 vs. 28.06 ± 4.57 kg/m2, p=0.02) after 1 year of treatment. Body composition, in terms of fat and fat-free mass, remained unchanged except for a significant elevation in body cell mass (25.50 ± 4.60 vs. 26.60 ± 3.17 kg, p=0.02). Basal levels of IR in the RA patients included in this study were significantly higher than healthy controls (1.6 ± 0.8 vs. 1.11 ± 0.56, p=0.011) but did not change during the follow-up. Nor did basal concentrations of adiponectin, visfatin, leptin, ghrelin, resistin, and apelin in response to anti-TNF-α treatment; only retinol-binding protein 4, showed a significant increase (51.7 ± 32.7 vs. 64.9 ± 28.4 µg/ml, p=0.03) at the end of the study. IR, adiposity distribution, and serum levels of most adipokines are not significantly affected by long-term inhibition of TNF-α in RA patients. Our data suggest that although systemic blockade of TNF-α exerts an anticachectic effect in RA patients, it does not seem to play a major role in IR.

An open-label pilot study of infliximab therapy in diffuse cutaneous systemic sclerosis.

AIM: The safety and potential efficacy of a chimaeric anti-tumour necrosis factor alpha monoclonal antibody (infliximab) were examined in diffuse cutaneous systemic sclerosis (dcSSc). METHODS: A 26-week open-label pilot study in which 16 cases of dcSSc received five infusions of infliximab (5 mg/kg). Clinical assessment included skin sclerosis score, scleroderma health assessment questionnaire, self-reported functional score and physician global visual analogue scale. Collagen turnover, skin biopsy analysis and full safety evaluation were performed. RESULTS: There was no significant change in skin score at 26 weeks but a trend for lower modified Rodnan skin score at 22 weeks (OR 17, 95% CI 6 to 46) compared with peak value (OR 29, 95% CI 11 to 44; p = 0.10). Serum aminoterminal propeptide of type III collagen level was significantly lower at week 26 compared with baseline (p = 0.03). Secretion of type I collagen by dermal fibroblasts was reduced at 26 weeks compared with baseline (p = 0.02). There were no deaths during the study and no suspected unexpected serious adverse reactions. 21 serious adverse events (AE) occurred in seven subjects, mostly attributable to dcSSc. 127 distinct AE occurred in 16 subjects. Of these, 19 AE (15%) were probably or definitely related to infliximab treatment. Eight (50%) patients prematurely discontinued infliximab. Anti-infliximab antibodies developed during the study in five subjects and were significantly associated with suspected infusion reactions (p = 0.025). CONCLUSION: In dcSSc infliximab did not show clear benefit at 26 weeks but was associated with clinical stabilisation and a fall in two laboratory markers of collagen synthesis. The frequency of suspected infusion reactions may warrant additional immunosuppression in any future studies in systemic sclerosis.

Permanent neonatal diabetes caused by a homozygous nonsense mutation in the glucokinase gene.

Glucokinase deficiency is an unfrequent cause of permanent neonatal diabetes (PND), as only seven patients have been reported, either homozygous for a missense or frameshift mutation or compound heterozygous for both of them. We report here the first known case caused by a homozygous nonsense mutation (Y61X) in the glucokinase gene (GCK) that introduces a premature stop codon, generating a truncated protein that is predicted to be completely inactive as it lacks both the glucose- and the adenosine triphosphate-binding sites. The proband, born to consanguineous parents, was a full-term, intra-uterine growth-retarded male newborn who presented with a glycaemia of 129 mg/dL (7.16 mmol/L) on his second day of life, increasing thereafter up to 288 mg/dL (15.98 mmol/L) and 530 mg/dL (29.41 mmol/L) over the next 24 h, in the face of low serum insulin (<3 muIU/mL; <20.83 pmol/L). He was put on insulin on the third day of life. Insulin has never been discontinued since then. The patient was tested negative for anti-insulin and islet cell antibodies at age 5 months. His father had non-progressive, impaired fasting glucose for several years. The mother was found to be mildly hyperglycaemic only when her glucose was checked after the child was diagnosed. In conclusion, biallelic GCK loss should be considered as a potential cause of PND in children born to consanguineous parents, even if they are not known to be diabetic at the time of PND presentation.

Contralateral lymph neck node metastasis of primary squamous cell carcinoma of the tongue: a retrospective analytic study of 203 patients.

In primary squamous cell carcinoma (SCC) of the oral cavity, many clinical and histopathological factors have been described as predictive for cervical lymph-node metastasis, but there are no data available on this association for surgical resection of lateral tongue primary SCC. The aim of this study was to analyse factors related to contralateral neck relapse in a series of 203 consecutive patients with SCC of the lateral aspect of the tongue treated by surgery with or without adjuvant radiotherapy. Several clinical features were analyzed. Histological study included pTNM classification, tumour size, surgical margins, extracapsular spread of lymph-node metastasis, perineural infiltration, peritumoral inflammation and bone involvement. The mean duration of follow up for surviving patients was 70.9+/-49.6 months; 47 patients eventually died of the disease and 116 patients are alive with no evidence of recurrence. The mean disease-specific survival time was 149+/-7 months. Twenty (9.8%) patients developed ipsilateral and nine (4.4%) contralateral neck recurrence. The mean period of time from surgery to contralateral neck recurrence was 11.4 months (range 3-27 months). Fourteen of the 20 ipsilateral and 8 of the 9 contralateral neck relapse patients eventually died of the disease. Histopathological grading and peritumoral inflammation were found to be statistically significant (P<0.05). Clinical and pathological lymph neck node status was not found to be associated with the appearance of contralateral lymph neck node relapse. Due to the increased risk of contralateral neck relapse within the first 2 years of surgery, close surveillance is mandatory at this time.

Radial forearm free flap for reconstruction of the oral cavity: clinical experience in 55 cases.

OBJECTIVE: Since the advent of modern microvascular techniques, the radial forearm free flap (RFFF) has become a reliable method for reconstruction of defects within the oral cavity. The purpose of the present study was to evaluate our experience with the use of the RFFF for the reconstruction of oral cavity defects after tumor resection. STUDY DESIGN: During a 9-year period, 103 consecutive patients were treated in our department for the reconstruction of oral defects after tumoral ablation by means of microvascularized free flaps. Fifty-five patients were reconstructed by means of the RFFF. Patients were treated for benign (n = 1) and malignant (n = 54) entities. All the patients underwent an abdominal split-thickness skin graft for the closure of the donor site. RESULTS: Fifty-five patients underwent reconstruction by means of the RFFF after resection of the oral cavity. Squamous cell carcinoma was present in 54 patients. A mean age of 55.5 years was observed (range 16-78). Thirty-nine patients (70.9%) were men and 16 (29.1%) women. Primary reconstruction was achieved in 52 patients (96.3%). A fasciocutaneous graft was used in all of the cases, with a mean size of 7.39 x 5.17 cm. The mean flap ischemic time was 56.02 minutes. During the immediate follow-up period, revision of the vascular anastomosis was necessary in 18.9% of the cases owing to flap ischemia. CONCLUSION: Our results revealed that the RFFF is a reliable method for reconstructing a wide range of oral cavity defects with an acceptable low morbidity rate. It provides adequate bulkiness and pliability, resulting in adequate reconstruction of a wide variety of defects within the oral cavity.

Intraoral mandibular distraction osteogenesis: special attention to treatment planning.

PURPOSE: To demonstrate our experience using internal devices for unidirectional distraction osteogenesis in treating different mandibular hypoplasias (with or without maxillary deformities). An algorithmic table for diagnosis, and treatment planning is presented. PATIENTS AND METHODS: Twenty internal distraction devices were used in 16 patients with mandibular hypoplasia. Deficiency in length of the mandible was calculated on three-dimensional computed tomography scans. The device was activated by a transcutaneous pin on the fifth postoperative day. Distraction was achieved at rates of 0.5 mm/12 h. After a variable period of consolidation the devices were removed. Mean follow-up was 18 months. RESULTS: Successful distraction osteogenesis was achieved in all patients. No premature consolidation or pseudoarthrosis was observed. Improvement of facial aesthetics was produced in all cases. Final occlusion was excellent in those cases where no simultaneous maxillary deformity was present. Orthodontic treatment was applied in all cases. Results remained stable one year postoperatively. CONCLUSIONS: The occlusal results obtained in this series show that we can plan distraction as a definitive treatment in cases with isolated mandibular hypoplasia. When an additional maxillary deformity is present, mandibular distraction must be performed first if indicated, but a maxillary procedure will be necessary later.

Vascularized free fibular flap for mandibular reconstruction: a report of 26 cases.

PURPOSE: Mandibular reconstruction represents a challenge to the oral and maxillofacial surgeon and has been revolutionized by the modern microvascular techniques. Rehabilitation using techniques such as reconstruction plates frequently produce a functional and cosmetic defect. The primary objective of the current study was to evaluate the usefulness of the osteomuscular free fibular flap for this purpose. PATIENTS AND METHODS: The results of 26 vascularized free fibula flaps with or without a skin paddle that were used for mandibular reconstruction is presented. The "double barrel" technique was used in 6 cases. The donor site was closed directly in 2 cases and with an abdominal full-thickness skin graft in 24 cases. RESULTS: All flaps except 1 were viable. There was partial necrosis of the skin island in 1 patient. The average length of the fibula graft was 10.96 cm, and the number of osteotomies ranged from 0 to 3. In the donor site, the most significant problem was unsatisfactory scarring related to the use of a skin graft. There were no long-term functional complications in the lower leg. Two patients have been secondarily rehabilitated with osseointegrated implants. CONCLUSION: The fibula flap provides a successful bone graft for mandibular restoration with an acceptably low complication rate. This method meets most of the requirements for oral and mandibular replacement.

Down-regulation of L-selectin expression in neutrophils by nonsteroidal anti-inflammatory drugs: role of intracellular ATP concentration.

L-selectin is an adhesion molecule that plays an essential role in the early events of the inflammatory response. Our group has recently described that several nonsteroidal anti-inflammatory drugs (NSAIDs) are able to induce both in vivo and in vitro the shedding of L-selectin in neutrophils through an unknown mechanism. In this work, we have studied potential mechanisms involved in the shedding of L-selectin induced by NSAIDs. This effect of NSAIDs did not involve any detectable intracellular calcium flux. Pretreatment of neutrophils either with Ro 31-8220 and H7, 2 specific inhibitors of protein kinase C (PKC), or with inhibitors of protein tyrosine kinases such as tyrphostin A25 or herbimycin A did not prevent the NSAID-mediated L-selectin shedding. However, the KD-IX-73-4, an inhibitor of L-selectin proteolysis was able to block the effect of NSAIDs on L-selectin expression. Remarkably, NSAIDs caused a variable reduction in the neutrophil intracellular ATP concentration that highly correlated with the differential ability of NSAIDs to trigger L-selectin shedding (r = 0.8, P <.01). In agreement with this finding, azide plus 2-deoxy-D-glucose, 2 metabolic blockers, also induced a rapid L-selectin shedding (65% +/- 8%) without affecting the neutrophil viability, activation, or expression level of other surface molecules with soluble isoforms such as CD16 and CD59. These data indicate that the maintenance of L-selectin on the neutrophil surface requires energy consumption, which suggests that L-selectin is shed in neutrophils by default. Interestingly, NSAIDs seem to cause the shedding of L-selectin, at least in part, through the reduction of the intracellular ATP concentration.

Distraction osteogenesis of the ascending ramus for mandibular hypoplasia using extraoral or intraoral devices: a report of 8 cases.

PURPOSE: This report presents the results of distraction osteogenesis using unidirectional extraoral and intraoral devices in 8 patients with different grades of vertical mandibular ramus hypoplasia. PATIENTS AND METHODS: Eight patients with hypoplastic mandibles underwent unilateral lengthening of the ascending ramus using unidirectional extraoral or intraoral devices. Intraoral mandibular distraction was performed on 5 patients with deficiencies of the vertical ramus up to 24 mm. External devices were used in 3 patients with more severe hypoplasias. An intraoral osteotomy was performed, and progressive distraction at rates of 0.5 mm/12 hours was initiated after 5 days. Once the desired length was reached, the device was maintained in place for 8 to 12 weeks. Three-dimensional computed tomography scans were taken in all the patients to plan the procedure and to compare the changes postoperatively. RESULTS: Successful distraction osteogenesis was achieved in all patients. The amount of mandibular lengthening ranged from 17 to 32 mm. Complications with the external devices such as rotation of the proximal bony fragment (2 cases) and loosening of the external screws at the end of the consolidation period (1 case) were observed. CONCLUSIONS: The results suggest that the intraoral device can be used as the method of choice for distraction osteogenesis of the ascending ramus of the mandible in patients with large deficiencies. Preoperative and postoperative 3-dimensional computed tomographic scans are essential in treatment planning.

A new transfacial approach for lesions of the clivus and parapharyngeal space: the partial segmented Le Fort I osteotomy.

Tumors of the clival and parapharyngeal areas are a challenge because of their location. They used to be considered inaccessible because the aggressive approaches employed caused elevated levels of morbidity. This fact led to more conservative approaches that attempted to preserve the exposure of the lesion. These approaches were a combination of cranial and facial procedures, thus utilizing a combined effort between neurosurgeons and maxillofacial surgeons. We described our experience with a partial segmented Le Fort I osteotomy added to a transmandibular approach to expose a chordoma of the clivus and left parapharyngeal space. A three-dimensional imaging was used as a diagnostic tool and to plan the optimal surgical approach. The operative technique was described in this case study. Some important technical details of the approach are described. The global outcome was favorable.

Tumor DNA content as a prognostic indicator in squamous cell carcinoma of the oral cavity and tongue base.

BACKGROUND: Nuclear deoxyribonucleic acid (DNA) content is a prognostic factor in several tumors, and decisions regarding treatment have been made using this parameter. Nevertheless, there is no agreement in head and neck cancer. The purpose of the present study was to ascertain whether tumor DNA content correlated with prognosis in cases of primary squamous cell carcinoma (SCC) of the oral cavity and tongue base. METHODS: A retrospective study of formalin-fixed, paraffin-embedded tissue from patients with histologically confirmed SCC of the oral cavity and tongue base was performed using flow cytometry. Tumor DNA content was studied in 109 sets of specimens from previously untreated patients. All of them underwent surgical resection at the University "Hospital de La Princesa" between 1982 and 1992. Clinical parameters (age, sex, site of primary tumor, clinical stage, adjuvant therapy received, and disease-free and overall survival) and histologic parameters (histopathologic stage, tumor differentiation, type of inflammatory infiltration, presence of perineural invasion) were recorded in all cases. An exhaustive statistical analysis was applied. RESULTS: Only the histograms of 93 patients were adequate for consideration. In flow cytometric analysis, DNA aneuploidy was observed in 51 tumors (55%). The proportion of aneuploid tumors was significantly higher in advanced-stage carcinomas (p < .05), tumors with perineural invasion (p < .05) and in men (p < .05). In the 24 patients with lymph node metastasis, the incidence of aneuploidy was 82% (19 of 24) (p < .05). The rate of metastasis and aneuploidy increased as the degree of differentiation decreased (p < .05 for both). Patients with aneuploid carcinomas in both early and advanced stages had shorter relapse-free and overall survival periods than did the patients with diploid tumors (p < .001 for both). A Cox regression analysis demonstrated that ploidy was the single most important prognostic factor in determining relapse and death (p < .001 for both). CONCLUSIONS: The results indicate that tumor DNA analysis by flow cytometry appears to be useful as a supplement to clinical and histologic evaluation in predicting the tendency of SCC of the oral cavity and tongue base to metastasize to regional lymph nodes and to predict the outcome of the disease.

Analysis of the tetraspanin CD9-integrin alphaIIbbeta3 (GPIIb-IIIa) complex in platelet membranes and transfected cells.

The platelet integrin, alphaIIbbeta3 (GPIIb-IIIa), and the tetraspanin, CD9, are integral membrane proteins that are abundant in platelet membranes. We have identified several proteins, including CD9, which were co-precipitated by anti-alphaIIbbeta3 antibody from untreated, resting platelets that were solubilized with the poly(oxyethylene) non-ionic detergent, Brij-35. Immunoblot and quantitative immunoprecipitation showed that the association of alphaIIbbeta3 with CD9 is specific and stoichiometric. The interaction between CD9 and alphaIIbbeta3 is probably hydrophobic, as Triton X-100 and hydrophobic detergents of the Brij series completely dissociated the CD9-alphaIIbbeta3 complex. Recombinant CD9 and alphaIIbbeta3 can associate after transfection into Chinese hamster ovary cells, as seen by co-immunoprecipitation and co-localization in the periphery of spreading cells and in the lamellipodia of cells plated on fibrinogen. This co-localization is absent from focal adhesions. Furthermore, anti-CD9-coated latex beads clustered alphaIIbbeta3 with CD9. This work indicates that the tetraspanin, CD9, is associated with beta3 integrins in resting platelets and transfected cells.

Squamous cell carcinoma of the oral cavity in patients younger than 40 years.

Squamous cell carcinoma of the head and neck has been regarded as a disease affecting the elderly. Several etiologic factors have been demonstrated, such as tobacco and alcohol use and premalignant lesions, whereas others have been suspected, such as genetic or immunodeficiency disorders. Recently, some reports have addressed a tendency toward an increase in the incidence of squamous cell carcinoma in young patients. In recent years we have observed an increase in the number of squamous cell carcinomas in patients younger than 40 years. Therefore we retrospectively reviewed our clinical experience of cancer in those patients younger than 40 years. After screening 505 clinical charts, 294 patients met the criteria to enter our study. Twenty-four (8.2%) patients were aged 40 years or younger. Data collected included the history of premalignant lesions, etiologic factors, TNM stages, treatment modalities, and histopathologic issues. Statistical analysis with Kaplan-Meier survival rates and log-rank tests between various variables were applied. A significant association in survival was observed between patterns of recurrence (p = 0.031) and presence of neoplastic cells 5 mm or closer to the specimen margin. On the other hand, a lack of association was assessed in carcinogenic-related habits and in premalignant lesions. Likewise, although men showed a slightly worse prognosis than women, statistically no significant differences were found (p = 0.27).

Prevention of cytokine-induced changes in leukocyte adhesion receptors by nonsteroidal antiinflammatory drugs from the oxicam family.

OBJECTIVE: To explore the effect of the nonsteroidal antiinflammatory drugs (NSAIDs) piroxicam and meloxicam on quantitative and qualitative changes in leukocyte adhesion receptors induced by cytokines and other activation stimuli. METHODS: The expression of CD11b and L-selectin during neutrophil activation with tumor necrosis factor alpha (TNF alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), FMLP, phorbol myristate acetate (PMA), and calcium ionophore A23187 was assessed by flow cytometry. Enzyme-linked immunosorbent assays were used to quantitate soluble L-selectin shed after neutrophil stimulation. Enzyme release was measured to determine neutrophil degranulation by proinflammatory stimuli. Changes in affinity state of beta 1 and beta 2 integrins after neutrophil and T lymphocyte stimulation were assessed, by flow cytometry, using the monoclonal antibodies (MAb) HUTS-21 (anti-beta 1) and CBRM1/5 (anti-CD11b), which recognize activation-dependent epitopes on these two integrins. RESULTS: Pretreatment of neutrophils with either NSAID prevented the changes in L-selectin and CD11b expression induced by TNF alpha, GM-CSF, and FMLP, but not those induced by PMA or A23187. Furthermore, piroxicam significantly decreased the amount of L-selectin shed by cytokine-treated neutrophils, whereas it did not exert this effect on PMA- or A23187-treated neutrophils. Piroxicam also decreased the release of gelatinase and lysozyme induced by TNF alpha, but not by PMA. Interestingly, piroxicam prevented the conformational changes that beta 2 integrins underwent upon activation of neutrophils: the appearance of the activation epitope of CD11b, detected by the CBRM1/5 MAb, was blocked by piroxicam in TNF alpha-treated neutrophils. Moreover, in chemokine-treated T lymphocytes, the expression of activation epitopes on beta 1 integrins was also diminished by piroxicam. In contrast, this NSAID did not affect the beta 1 integrin conformational changes induced by PMA or Mn++. CONCLUSION: Our results indicate that members of the oxicam family are able to interfere with events of neutrophil function, such as their degranulation and cytokine-mediated activation changes in adhesion molecules, both in neutrophils and in lymphocytes. Such effects may significantly contribute to the antiinflammatory activity of these drugs.

Aceclofenac, a new nonsteroidal antiinflammatory drug, decreases the expression and function of some adhesion molecules on human neutrophils.

OBJECTIVE: To study the effect of aceclofenac, a new nonsteroidal antiinflammatory drug (NSAID), on the expression and function of adhesion molecules in human neutrophils. METHODS: We used flow cytometry analysis to determine peripheral blood neutrophil expression of L-selectin, CD11a, CD11b, CD31, CD43, CD44, and intercellular adhesion molecule 2 (ICAM-3) surface adhesion molecules after treatment with aceclofenac, diclofenac, or dexamethasone. Granular enzyme activity was quantitated in extracellular medium of neutrophils treated with different NSAID: In vitro adhesion assays were developed to examine the effects of aceclofenac on both neutrophil adhesion to tumor necrosis factor alpha stimulated human umbilical vein endothelial cells under nonstatic conditions, and homotypic neutrophil aggregation induced by anti-ICAM-3 and anti-CD18 monoclonal antibodies (Mab). RESULTS: Aceclofenac induced a dramatic decrease of L-selectin expression, whereas a moderate and slight decrement of CD43 and ICAM-3 expression was also observed. In contrast, the expression of other adhesion molecules by neutrophils was unaffected (CD11a, CD31, CD44) or slightly increased (CD11b). Cell adhesion assays, performed under nonstatic conditions, revealed that aceclofenac significantly diminished the L-selectin dependent neutrophil adhesion to endothelial cells. Neutrophil aggregation induced with anti-CD43 Mab was also significantly inhibited by aceclofenac. CONCLUSION: Aceclofenac had a faster and more potent effect than the other NSAID studied, mainly on the expression of cell adhesion molecules. This new NSAID efficiently interferes with neutrophil adhesion to endothelium and this effect may represent an additional relevant mechanism in its antiinflammatory activity.

Beta 3 integrin-mediated fibrin clot retraction by nucleated cells: differing behavior of alpha IIb beta 3 and alpha v beta 3.

Fibrin clot retraction may be important in resolution of thrombi and, in platelets, is mediated by integrin alpha IIb beta 3 (GPIIb-IIIa). Nucleated cells that lack alpha IIb beta 3 can retract fibrin clots, and we now report that integrin alpha v beta 3 can support this process. In addition, we compared the capacities of recombinant beta 3 integrins to mediate clot retraction in Chinese hamster ovary and M21 melanoma cells. We found that alpha v beta 3, but not alpha IIb beta 3, could spontaneously support retraction. Transferring the cytoplasmic domain of alpha v to alpha IIb enabled the resulting chimeric alpha IIb beta 3 to support clot retraction. The capacity of the alpha v cytoplasmic domain to support clot retraction was not caused by activation of the ligand binding function of alpha IIb beta 3 or by enhancement of alpha IIb beta 3's capacity to stimulate the formation of focal adhesions or the tyrosine phosphorylation of pp125FAK. These experiments define requirements for alpha IIb beta 3-mediating clot retraction, establish the capacity of alpha v beta 3 to mediate this process, and suggest differing functional roles of the alpha v and alpha IIb cytoplasmic domains.

Adhesion molecules from the LFA-1/ICAM-1,3 and VLA-4/VCAM-1 pathways on T lymphocytes and vascular endothelium in Graves' and Hashimoto's thyroid glands.

Lymphocytic infiltration of the thyroid gland in autoimmune thyroid disorders requires, as a first step, their attachment to endothelial cells (EC) and subsequently, their interaction with thyrocytes and extracellular matrix proteins. A number of different ligand molecules have been identified to mediate the interaction between EC and leukocyte subpopulations. In this study, we examined by flow cytometry and immunohistochemical techniques, the expression of integrin receptors and their counter-receptors by infiltrating lymphocytes and vascular endothelium in thyroid glands from patients with Graves' disease (GD) and Hashimoto's thyroiditis (HT). A high proportion of GD intrathyroidal T lymphocytes expressed the CD69 and gp95/85 (Ea2) activation antigens as well as an increased number of LFA-alpha L, VLA-alpha 1, -alpha 4, -alpha 5, and beta 1 integrin receptors, as compared with peripheral blood T lymphocytes from the same patients. The expression of intercellular adhesion molecule (ICAM)-1 was increased in EC from GD and HT thyroids. In addition, an up-regulated de novo expression of vascular cell adhesion molecule (VCAM)-1 was found in EC in GD and HT thyroids, with no reactivity in control thyroids. Dendritic cells in thyroid lymphoid follicles were also positive for ICAM-1 and VCAM-1. In addition, most of intrathyroidal mononuclear cells expressed the ICAM-3 adhesion molecule. This enhanced expression of ICAM-1 and VCAM-1 by thyroid EC in GD and HT may reflect their ability to regulate leukocyte trafficking and activation by means of the expression of specific ligand molecules. Our data suggest that both the LFA-1/ICAM-1, ICAM-3 and VLA-4/VCAM-1 pathways could play a relevant role in localizing and perpetuating the autoimmune response in the thyroid gland in autoimmune thyroid disorders.