Expression of MMPs and TIMP-1 in smoker and nonsmoker chronic periodontitis patients before and after periodontal treatment.

BACKGROUND AND OBJECTIVE: Nonsurgical periodontal treatment controls periodontal inflammation. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are implicated both in the destruction and in the healing of periodontal tissues. The aim of the present study was to compare the mRNA expression of MMP-1, -3, -8, -9 and -13 and TIMP-1 in chronic periodontitis before and after initial periodontal treatment. MATERIAL AND METHODS: Ninety gingival samples were harvested from 30 patients with chronic periodontitis (15 nonsmokers and 15 smokers) before and after nonsurgical treatment and from 30 periodontally healthy control subjects (15 nonsmokers and 15 smokers). Clinical parameters were assessed before and after treatment. Total RNA was isolated, and mRNA expression of MMPs and TIMP-1 was assessed by RT-PCR. RESULTS: Periodontal treatment significantly increased TIMP-1 expression and decreased the ratios of MMPs/TIMP-1. Post-treatment, nonsmokers with periodontitis had significantly higher MMP-8 and TIMP-1 expression than healthy nonsmokers, and smokers with periodontitis had significantly higher MMP-13 and TIMP-1 expressions than healthy smokers. Post-treatment, smokers had significantly higher TIMP-1 expression and lower MMP-8/TIMP-1 ratio than nonsmokers. Post-treatment, there was no correlation among MMPs, and the expression of MMPs and TIMP-1 was not correlated with clinical measurements. CONCLUSION: Periodontal treatment increased TIMP-1 expression and decreased the ratios of MMPs/TIMP-1 in chronic periodontitis. The post-treatment increase in TIMP-1 expression was higher for smokers. The TIMP-1 expression was higher post-treatment than in health. Post-treatment, MMP-8 expression was higher in nonsmokers with periodontitis than in healthy nonsmokers, whereas MMP-13 expression was higher in smokers with periodontitis than in healthy smokers.

The effect of smoking on the mRNA expression of MMPs and TIMP-1 in untreated chronic periodontitis patients: a cross-sectional study.

BACKGROUND AND OBJECTIVE: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are important for extracellular matrix. Expression of MMPs has been evaluated in gingiva without studying smoking. The aim of this study was to explore the effect of smoking on mRNA expression of MMP-1, -3, -8, -9 and -13 and TIMP-1 in untreated chronic periodontitis and in periodontal health. MATERIAL AND METHODS: Gingival samples were harvested from 30 subjects with untreated chronic periodontitis (15 nonsmokers and 15 smokers) and 30 periodontally healthy subjects (15 nonsmokers and 15 smokers). Full-mouth plaque score, gingival index, bleeding on probing, probing depth and clinical attachment level were recorded. Total RNA was isolated, and the mRNA expression of MMPs and TIMP-1 was assessed by RT-PCR. RESULTS: Periodontitis groups were comparable in clinical measurements. Nonsmoker subjects with periodontitis had statistically significantly higher MMP-1, lower MMP-9 and TIMP-1 expression and higher MMP-1/TIMP-1 ratio than smokers; and higher MMP-8 expression and MMP-8/TIMP-1 and MMP-1/TIMP-1 ratios than healthy nonsmokers. Healthy nonsmokers had statistically significantly higher MMP-13 expression than healthy smokers. Smoker periodontitis and healthy subjects had similar expression levels of MMPs and TIMP-1 and MMPs/TIMP-1 ratios. There was correlation among the MMPs only for smoker periodontitis subjects. Expression of MMP-13 was correlated with mean clinical attachment level. CONCLUSION: Within its limits, this study demonstrated that smoking affected mRNA expression of MMPs and TIMP-1, MMPs/TIMP-1 ratios and relationships among MMPs in untreated chronic periodontitis and expression of MMPs in health. In the absence of smoking, chronic periodontitis affected expression of MMPs and MMPs/TIMP-1 ratios.

Syndecan-1 immunohistochemical expression in gingival tissues of chronic periodontitis patients correlated with various putative factors.

BACKGROUND AND OBJECTIVE: Limited information is available on the expression and distribution of syndecan-1 within human gingival tissues/cells and on putative factors that might affect its expression. Therefore, the objective of the present study was to determine immunohistochemically the expression and distribution of syndecan-1 in the gingival tissues of patients with chronic periodontitis and to examine the correlation of syndecan-1 expression with various putative factors (environmental, patient/systemic and local factors). MATERIAL AND METHODS: Gingival specimens were surgically excised from the area of the junctional/pocket epithelium (study group 1, including 30 chronic periodontitis patients) or the gingival oral epithelium (study group 2, comprising another 30 chronic periodontitis patients), adjacent to teeth with poor prognosis. Standard two-step immunohistochemistry and semi-quantitative evaluation of immunohistochemical staining were used to determine syndecan-1 expression. Statistical analyses on the impact of various putative factors were performed. RESULTS: In the junctional/pocket epithelium or the oral epithelium, syndecan-1 expression was weak to moderate in the suprabasal and basal epithelial cells and absent to weak in the internal basal lamina, external basal lamina and gingival connective tissue matrix. Syndecan-1 expression in the junctional/pocket epithelium was statistically significantly stronger than in the oral epithelium in inflammatory cells within the underlying gingival connective tissue (primarily plasma cells and lymphocytes) and in scattered fibroblast-like cells. CONCLUSIONS: Syndecan-1 expression in the junctional/pocket epithelium or the oral epithelium can exhibit a significant positive correlation with the severity/degree of histologically evaluated local gingival inflammation, but in general is not significantly correlated with age, smoking, full-mouth and local clinical (probing pocket depth and clinical attachment level) and radiographical parameters (radiographical bone loss) of periodontal status.

Brown tumor of the fibula: unusual presentation of an uncommon manifestation. Report of a case and review of the literature.

Brown tumors are erosive bony lesions caused by rapid osteoclastic activity and peritrabecular fibrosis due to hyperparathyroidism, resulting in a local destructive phenomenon. Although brown tumors are the most pathognomonic sign of hyperparathyroidism, they are very rarely observed at present as a result of early detection of hypercalcemia and elevated parathyroid hormone levels. The rare appearance of this entity in everyday practice is troublesome for both patients and physicians, because whenever it emerges, diagnosis could be mistaken for a giant cell tumor of the bone. However, clinical, biochemical, and radiologic findings can easily guide the diagnosis if one considers the full continuum of findings and their association with subject's medical history, instead of focusing only on bone lesion. In this report we present a case of brown tumor in the fibula with a short literature review, whose aggressive presentation and unawareness of the skeletal findings of hyperparathyroidism puzzled the caring doctors. This case illustrates the need for continuous vigilance of any physician, regardless of his specialty or his position in medical services structures.

Tenascin-C protein expression and mRNA splice variants in thyroid carcinoma.

Tenascin-C (Tn-C) is a matricellular protein involved in the initial and intermediate stages of cell adhesion. The present study is the first undertaken to comparatively investigate Tn-C in neoplastic, non-neoplastic thyroid lesions and normal thyroid tissues. Forty-eight thyroid specimens were studied immunohistochemically using a monoclonal antibody against Tn-C. Immunohistochemistry was supplemented by RT-PCR analysis of the two Tn-C mRNA splice variants in 13 thyroid cancer cell lines. Normal and non-neoplastic tissues were devoid of Tn-C, as well as follicular neoplasms, Huerthle-cell and anaplastic carcinomas. Most papillary carcinomas showed a focally intensive extracellular staining, localized in the connective tissue stroma, whereas most medullary carcinomas showed a staining in the connective tissue but also in intracellular location mainly. RT-PCR analysis detected Tn-C mRNA in all thyroid cancer cell lines with prevalence of the large splice variant in all but the medullary line, characterized by a higher Tn-Csmall:Tn-Clarge ratio. In conclusion, Tn-C re-expression has been observed in papillary and medullary thyroid carcinomas with different staining patterns accompanied by the prevalence of different mRNA splice variants in cell cultures. It seems possible that Tn-C is rather synthesized by tumor cells than by activated stromal cells.

The development of the chicken small intestine: a scanning electron microscopy study.

The surface pattern of the small intestine of the chicken was studied using SEM in stages ranging from 11th day of foetal development to 60 days of post-natal life. The definite villi of the small intestine were preceded by the development of the previllous ridges. The villi were finger like and of unequal length during incubation. After hatching, gradually, the villi were longer, well formed with furrows along their sides. Respectively, the crypts, being present at late incubation, increased with age. Columnar epithelial cells with dense microvilli lined the luminal surface of the intestine with obvious goblet cells openings among them.

Immunohistochemical detection of cell cycle regulators, Fhit protein and apoptotic cells in parathyroid lesions.

OBJECTIVE: The pathological distinction between parathyroid neoplasms and hyperplasias remains difficult. Changes in cell cycle control may lead to clonal proliferation and precede tumorigenesis. The parathyroid adenoma 1 oncogene, subsequently identified as the gene encoding cyclin D1, has been shown to be important to parathyroid tumour development. In addition to cell proliferation, the mechanisms of parathyroid cell turnover include apoptosis. The tumour-suppressor activity of the fragile histidine triad gene (FHIT) is linked to its proapoptotic function and cell cycle control. We attempted to evaluate the cellular proliferative kinetics and apoptotic function of the parathyroid glands in patients with non-familial hyperparathyroidism (HPT). DESIGN: TIssue specimens were taken from 40 patients with primary HPT (17 adenomas, two carcinomas and 21 primary hyperplasias) and from 30 patients with secondary HPT. Normal glands served as controls. METHODS: In a standard immunohistochemical procedure, monoclonal antibodies to Ki-67 antigen and single-stranded DNA were applied to detect cycling and apoptotic cells respectively; polyclonal antibodies to cyclin D1 and Fhit protein were used. Immunostaining was estimated by image analysis and statistical analysis was subsequently performed. RESULTS: Significantly higher proliferative and apoptotic indexes were detected in the diseased glands in comparison with normal controls. In neoplastic and secondarily hyperplastic glands, apoptotic indexes were higher than in primarily hyperplastic glands; the difference between neoplastic and primarily hyperplastic glands was statistically significant (P=0.034). Cyclin D1 was overexpressed in a considerable proportion of tumours (68.4%). A reduction of Fhit protein immunoreactivity was selectively noticed in carcinomas. CONCLUSIONS: In primary hyperplasia, the remarkable proliferation of parathyroid glands may be due to the reduction of the apoptotic process. FHIT gene abnormalities are worthy of investigation in parathyroid carcinogenesis.

Pre-operative Tc-99m-sestamibi scanning and intra-operative nuclear mapping: are they accurate in localizing parathyroid adenomas?

PURPOSE: Presentation of the results of Tc-99m-sestamibi imaging in the pre-operative localization of parathyroid adenomas and the intra-operative localization of those lesions using a gamma detector (prospective study). PATIENTS & METHODS: Eighteen consecutive patients aged 27-75 years with primary hyperparathyroidism (PHPT) underwent Tc-99m-sestamibi scanning 1-2 hours before the operation and the presence of a single adenoma was recognized. All our patients underwent bilateral neck exploration based on pre-operative scanning and intra-operative gamma detector guidance and the adenoma was detected in the positions shown by both methods. RESULTS: In 16 patients we found a single adenoma localized in the same position shown by pre-operative scanning, while the intra-operative method accurately revealed all abnormal glands. In one of the two patients where an inaccurate pre-operative localization technique had been carried out, we performed thyroid lobectomy (the adenoma proved to be intrathyroidal), while the other one had an adenoma which was not close to the site indicated by the pre-operative scintigraphy. Serum calcium reverted to normal within a few days postoperatively. CONCLUSION: Patients with true-positive scans for single parathyroid adenoma could be eligible for minimally invasive operations since the abnormal gland is easily identified by the above-mentioned methods.

Scanning electron microscopic observations of the development of the chicken caecum.

The surface pattern of the caeca of the chicken was examined using the scanning electron microscope (SEM) in stages ranging from 11th day of foetal development to 60 days of post-natal life. During incubation the proximal region (basis) of the caecum presented a few irregular elevations, which were later regarded as villi and after hatching, gradually, became longer and wider. These structures were found to be similar to those of the small intestine. The middle (corpus) and distal (apex) regions of caecum presented ridges/folds with short and blunt villi that were even shorter in the apex. The ridges/folds were running longitudinally the inner surface of the corpus while those of the apex were not so well developed.

Computerized nuclear morphometry and quantitation of angiogenesis in thyroid neoplasms.

The aim of this study was to investigate the nuclear and angiogenetic profile in different types of thyroid neoplasms and to make any possible statistical comparison between the different nuclear morphometric and angiogenetic parameters, in order to search for new diagnostic and prognostic criteria. Sixty two cases of thyroid neoplasms were classified as follows: 31 papillary carcinomas, 10 follicular neoplasms (5 adenomas and 5 carcinomas), 5 undifferentiated carcinomas, 6 Huerthle-cell carcinomas and 10 medullary carcinomas. Using an image analysis system, six nuclear morphometric and eight angiogenetic variables were measured for each case. Concerning nuclear morphometric variables, statistical differences were found mainly between undifferentiated and overall subtypes of differentiated carcinomas, as well as between follicular adenomas and carcinomas. Concerning angiogenesis variables, statistical differences were found only in the vessel's minor axis length between undifferentiated and overall subtypes of differentiated carcinomas, between MVD of follicular adenomas and carcinomas respectively, as well as between MVD of medullary carcinoma and follicular cell carcinomas generally. In conclusion nuclear morphometry and quantitation of angiogenesis could offer two additional parameters in the distinction between follicular adenomas and carcinomas. However, they cannot serve as absolute diagnostic criteria since they are only based on statistical differences. From a prognostic point of view, nuclear morphometry may have some relevance as far as follicular-cell neoplasms are concerned since the more aggressive anaplastic carcinomas have a distinct morphometric profile. Moreover, our study revealed differences in the angiogenetic profile between medullary and follicular cell carcinomas.

Thyroid gland neurofibroma in a NF1 patient.

Neurofibromas are a hallmark of neurofibromatosis type 1 (NF1). They are usually benign and rarely present in the thyroid gland region. There is a suspected association between NF1 and intramedullary thyroid carcinoma and there is a well-known association between NF1 and pheochromocytoma. Here, we present a 55-year-old man with typical symptoms of NF1, whose course was complicated by a neurofibroma of the thyroid gland. His clinical spectrum of symptoms included bilateral cataract established before the age of 35 years, quadriparesis and an intrathoracic mass. The patient died because of abdominal carcinomatosis of unknown origin. The rarity of thyroid gland neurofibroma is discussed here, emphasizing the importance of early detection of these and other NF1 complications, also including the risk of malignant transformation with lethal outcome.

Immunodetection and clinico-pathological correlates of two tumour growth regulators in laryngeal carcinoma.

Activation of telomerase, present in the vast majority of all human cancers, is associated with elongation of chromosomal telomeres and consequent cell immortalization. Telomere length homeostasis is a dynamic process governed by the negative feedback mechanism of the telomeric repeat binding factor 1 (TRF1) which inhibits the action of telomerase in telomerase-positive cells. In an attempt to investigate markers of tumour growth as possible prognostic indicators in laryngeal cancer, we studied the expression of TRF1 and of the proliferation marker Ki67 on 96 invasive squamous carcinomas of the larynx. A standard three step immunoperoxidase staining method was applied on paraffin sections incubated with appropriate polyclonal antibodies. The percentages of Ki67- and TRF1-immunopositive cancerous cells were calculated by image analysis. Univariate and multivariate statistical analysis of the staining results were performed in order to detect any association of the examined immunomarkers with the tumours' classical clinicopathological variables including nuclear morphometric features as well as with patients' disease-free survival. Ki67 immunostaining was positively linked with advanced patients' age, nodal involvement as well as presence of early recurrence. No relation was found between proliferative fraction and TRF1 immunoexpression. TRF1 was expressed in 55.2% of all cases and was positively linked only to tumour size. Multivariate statistical analysis revealed the presence of lymph nodal metastasis and Ki67 immunopositivity index > or = 20% as significant predictors of relapse. Increased Ki67 immunostaining appears to be a promising marker of tumour aggressiveness in laryngeal cancer. After one point at the tumour's natural history, the maintenance of tumour growth does not seem to depend on cell proliferation but on TRF1 immunoexpression. Whether the latter can be used for the identification of immortalized cells in every-day practice is worth investigating.

High plasma amylin/islet amyloid polypeptide levels in patients with residual medullary thyroid carcinoma after total thyroidectomy.

OBJECTIVE: We have previously reported that amylin/islet amyloid polypeptide (IAPP) mRNA is detected in a substantial subset of medullary carcinomas of the thyroid (MTCs). The aim of this study was to determine if the amylin/IAPP gene is expressed as the IAPP peptide in MTC tissues. DESIGN AND METHODS: In 10 patients with a histological diagnosis of MTC and with persisting or recurrent disease (basal calcitonin levels >250 pg/ml), the fasting serum insulin and plasma glucose, IAPP and calcitonin levels were measured and compared with those of 18 normal control subjects matched for age and body mass index. IAPP expression was studied by immunohistochemistry in MTCs and lymph-node metastasis tissues. RESULTS: Seven of ten MTC patients had abnormally elevated IAPP levels. Plasma IAPP and serum insulin levels were correlated in both patients and controls, but the slope of the regression line was significantly higher for MTC patients. IAPP staining was detected in four out of 12 random MTC samples and in two out of five lymph-node metastases, using immunohistochemistry. CONCLUSIONS: These results indicate that MTC cells express IAPP at the peptide level and that this raises the peripheral plasma levels. Further studies may reveal whether this is a feature of malignant disease.

Autoimmune thyroid disease in women with breast carcinoma.

AIMS: Estimation of prevalence of autoimmune thyroid disorders in Greek breast cancer patients (prospective study). METHODS: The prevalence of autoimmune thyroiditis was estimated in 310 Greek breast cancer patients, in 100 women with benign breast disease and in 190 women without any breast disease, by submitting them to clinical examination, ultrasound thyroid evaluation, serum thyroid antibody determination and fine needle aspiration (FNA) of the thyroid gland. RESULTS: Autoimmune thyroiditis was found in 136/310 (43.9%) breast cancer women: 95 were diagnosed by positive autoantibodies, 19 had positive FNA findings and 22 had both positive autoantibodies and positive FNA findings. In 117 cases, thyroid autoantibodies were positive (37.7% whereas the control groups had respective rates of 19% and 18.4% autoantibody positivity). CONCLUSIONS: There is evidence of high incidence of autoimmune thyroiditis in Greek breast cancer patients, increasing in relation to cancer stage.

Circulating thyroglobulin transcytosed by thyroid cells in complexed with secretory components of its endocytic receptor megalin.

After its endocytosis from the colloid, some thyroglobulin (Tg) is transcytosed intact across thyrocytes, accounting in part for its presence in the circulation. We previously showed that megalin (gp330), an endocytic Tg receptor, mediates apical to basolateral Tg transcytosis. Here we investigated whether a portion of megalin remains combined with Tg after its transcytosis, using studies with cultured thyroid cells and in vivo observations. FRTL-5 cells, a rat thyroid cell line, cultured on filters in dual chambers form tight junctions and exhibit features of polarity, with expression of megalin exclusively on the upper (apical) surface. After the addition of unlabeled Tg to the upper chamber and incubation at 37 C, some Tg was transcytosed intact across FRTL-5 cells into the lower chamber. Two antimegalin ectodomain antibodies precipitated transcytosed Tg in fluids collected from the lower chamber. After the addition of Tg to surface-biotinylated FRTL-5 cells, an anti-Tg antibody and the two antimegalin ectodomain antibodies precipitated high molecular mass biotinylated material in fluids collected from the lower chamber, corresponding to much of the megalin ectodomain, as well as smaller amounts of lower molecular mass material. The results indicate that Tg transcytosed across FRTL-5 cells remains complexed with megalin ectodomain components, which we refer to as megalin secretory components. In aminotriazole-treated rats, which develop increased megalin-mediated Tg transcytosis, antimegalin antibodies precipitated some of the Tg in the serum. Tg was also precipitated by antimegalin antibodies in sera from patients with Graves' disease, in which we found increased megalin expression on the apical surface of thyrocytes. In contrast, in thyroidectomized patients with metastatic papillary thyroid carcinoma, in whom Tg is directly secreted by neoplastic thyroid cells into the circulation rather than transcytosed, serum Tg was not precipitated by antimegalin antibodies. The detection of Tg-megalin complexes may help identify the source of serum Tg in patients with thyroid diseases.

Fas ligand expression in thyroid follicular cells from patients with thionamide-treated Graves' disease.

Thionamides are used in the treatment of Graves' disease (GD) and act mainly by inhibiting the organification of iodide, but also lower the levels of thyroid autoantibodies, sometimes leading to long-term remission. Fas ligand (FasL) induces apoptosis of susceptible cells by cross-linking its own receptor, Fas. While Fas is present in a wide variety of normal tissues, FasL expression is limited mainly to cells of the immune system, where it acts as an effector molecule of cell-mediated cytotoxicity, and to the placenta, brain, eye, and testis where it presumably contributes to their immune-privileged status by eliminating infiltrating lymphocytes. We examined immunohistochemically the presence of FasL in thyroid tissue from 15 glands of thionamide-treated GD patients and in 8 normal thyroid control specimens. We also investigated the presence of FasL in thionamide-treated thyrocytes in vitro and their ability to induce Fas-mediated apoptosis in lymphocytes. We found that FasL expression was very weak to undetectable in normal thyroid tissue and cultured thyrocytes, whereas it was strong in thionamide-treated GD glands and cultured thyrocytes. Methimazole-treated thyrocytes induced FasL-dependent apoptosis in cocultured lymphocytes, whereas methimazole treatment of lymphocytes grown in the absence of thyrocytes had no such effect. We conclude that FasL is highly expressed in follicular cells of thyroid glands obtained from thionamide-treated Graves' patients and may contribute to the immunomodulatory effect of thionamides in this disease.

Computerized morphometric study on fine needle aspirates of cellular follicular lesions of the thyroid.

OBJECTIVE: To investigate the value of computerized nuclear morphometry in the differential diagnosis of cellular follicular lesions of the thyroid cytologically diagnosed on fine needle aspiration (FNA) smears. STUDY DESIGN: Sixty cases of FNA thyroid smears were cytologically diagnosed and classified as follows: 30 cases of follicular carcinoma, 20 cases of cellular hyperplastic nodules and 10 cases of follicular adenoma. Using an image analysis system, two morphometric variables, nuclear area and major axis length of the nucleus, were measured for each case. RESULTS: For both nuclear morphometric variables, statistical differences were found between carcinomas and hyperplastic nodules as well as between carcinomas and adenomas. No statistical differences were found between the nuclear variables in either hyperplastic nodules or adenomas. CONCLUSION: The results confirm the aim of our study, to establish nuclear morphometry by computerized image analysis as an additional tool in the differential diagnosis of thyroid follicular lesions cytologically diagnosed on FNA smears.

Thyroid carcinoma cells are resistant to FAS-mediated apoptosis but sensitive to tumor necrosis factor-related apoptosis-inducing ligand.

Fas (APO-1/CD95) is a transmembrane protein of the tumor necrosis factor (TNF)/nerve growth factor receptor superfamily that induces apoptosis in susceptible normal and neoplastic cells upon cross-linking by its ligand (FasL). TNF-related apoptosis-inducing ligand (TRAIL) is a more recently identified member of the TNF superfamily that has been shown to selectively kill neoplastic cells by engaging two cell-surface receptors, DR4 and DR5. Two additional TRAIL receptors (DcR1 and DcR2) do not transmit an apoptotic signal and have been proposed to confer protection from TRAIL-induced apoptosis. We addressed the expression of Fas, DR4, and DR5 in thyroid carcinoma cell lines and in 31 thyroid carcinoma specimens by Western blot analysis and immunohistochemistry, respectively, and tested the sensitivity of thyroid carcinoma cell lines to Fas- and TRAIL-induced apoptosis. Fas was found to be expressed in most thyroid carcinoma cell lines and tissue specimens. Although cross-linking of Fas did not induce apoptosis in thyroid carcinoma cell lines, Fas-mediated apoptosis did occur in the presence of the protein synthesis inhibitor cycloheximide, suggesting the presence of a short-lived inhibitor of the Fas pathway in these cells. Cross-linking of Fas failed to induce recruitment and activation of caspase 8, whereas transfection of a constitutively active caspase 8 construct effectively killed the SW579 papillary carcinoma cell line, arguing that the action of the putative inhibitor occurs upstream of caspase 8. By contrast, recombinant TRAIL induced apoptosis in 10 of 12 thyroid carcinoma cell lines tested, by activating caspase-10 at the receptor level and triggering a caspase-mediated apoptotic cascade. Resistance to TRAIL did not correlate with DcR1 or DcR2 protein expression and was overcome by protein synthesis inhibition in 50% of the resistant cell lines. One medullary carcinoma cell line was resistant to Fas-and TRAIL-induced apoptosis, even in the presence of cycloheximide, and to transfection of constitutively active caspase-8, suggesting a different regulation of the apoptotic pathway. Our observations indicate that TRAIL effectively kills carcinomas that originate from the follicular epithelium of the thyroid gland, by inducing caspase-mediated apoptosis, and may provide a potentially potent therapeutic reagent against thyroid cancer.

The effect of iodine administration on the development of thyroid autoimmunity in patients with nontoxic goiter.

OBJECTIVE: Previous studies, mostly performed in iodine-deficient areas, have suggested that the administration of iodine to patients with endemic goiter may be associated with the development of thyroid autoantibodies (ThAbs); however, this has not been a consistent finding. In this study, we evaluated the effect of iodine on thyroid function and on the development of indices of autoimmunity (ThAbs and lymphocytic infiltration) in an iodine replete area. METHODS: Iodized oil (1 mL) was administered intramuscularly to 40 euthyroid patients with nontoxic goiter, adequate iodine intake, and absent or normal levels of ThAbs. Blood and urinary samples were taken at time 0, 3, 6, and 12 months after iodine administration. Thyroid volume was evaluated and fine-needle aspiration (FNA) was performed at 0, 6, and 12 months. RESULTS: Seven patients developed abnormal levels of ThAbs at some time between 3 and 12 months after iodine administration (p = 0.017). Mean anti-thyroglobulin (Tg) antibody levels increased at 6 months without reaching abnormal levels, but did not reach statistical significance (p = 0.062). Lymphocytic infiltration was detected in FNA smears in 10 cases before and in 27 cases after treatment (p = 0.0003). Triiodothyronine (T3) decreased at 12 months of follow-up, while thyroxine (T4) and thyrotropin (TSH) levels did not change significantly. A decrease in the mean levels of thyroglobulin as well as a small reduction in goiter size was observed at 6 and 12 months. CONCLUSION: The administration of iodized oil to patients with small nontoxic goiter in an iodine-replete area was accompanied by the development of abnormal levels of ThAbs in some cases and by an increase in thyroid lymphocytic infiltration.

In situ expression of E-selectin and intercellular adhesion molecule-1 in chronic inflammatory diseases of the gastrointestinal tract.

AIM: The study of cell adhesion molecules contributes to our understanding of the inflammatory mechanisms which include the endothelial activation of newly formed or pre-existing vessels, the increase of inflammatory cells' adhesive capability and their migration into perivascular tissues. The aim of the present study was to investigate the local presence and the extent of expression of E-selectin and intercellular adhesion molecule-1 (ICAM-1) in the mucosa of patients with chronic gastritis, chronic inflammatory bowel disease, and controls, as well as to identify possible correlations between in situ expression of the above adhesion molecules and degree of inflammatory activity or therapeutic response. DESIGN: In cryostat tissue sections we examined the immunohistochemical expression and localization of E-selectin and the intercellular adhesion molecule-1 (ICAM-1). Our specimens consisted of 27 cases of chronic gastritis, 42 cases of ulcerative colitis, and 15 cases of Crohn's disease. RESULTS: E-selectin was expressed in capillary endothelia as well as on neutrophils, located either in the lamina propria or in the glandular epithelia or lumina. This marker's expression was associated with the active phase of ulcerative colitis (p<0.0005) and possibly of chronic gastritis (p=0.06). ICAM-1 immunolabelling was localized in endothelia and chronic inflammatory components which had passed through the vascular walls. This marker's immunoreactivity was generally increased in all our specimens compared to normal mucosa and generally tended to correlate with chronic phases of the inflammatory process (p<0.10). CONCLUSIONS: E-selectin regulates the accumulation of neutrophils in the early stages of the inflammatory process and is thus associated at least with the active phase of ulcerative colitis. Whether any post-therapy alteration of E-selectin immunopositivity seems to indicate a good response to drug therapy is well worth investigating in ulcerative colitis patients. ICAM-1 immunoreactivity in lymphoplasmacytic infiltrates might serve as a marker of chronic immune stimulation, which is potentially responsible for the persistence of the inflammatory disorders.