Thyroid carcinomas comprise a broad spectrum of tumors with different clinical behaviors. On the one side, there are occult papillary carcinomas (PTC), slow growing and clinically silent, and on the ...other side, rapidly growing anaplastic carcinomas (ATC), which are among the most lethal human neoplasms. We have analysed the microRNA (miR) profile of ATC in comparison to the normal thyroid using a microarray (miRNACHIP microarray). By this approach, we found an aberrant miR expression profile that clearly differentiates ATC from normal thyroid tissues and from PTC analysed in previous studies. In particular, a significant decrease in miR-30d, miR-125b, miR-26a and miR-30a-5p was detected in ATC in comparison to normal thyroid tissue. These results were further confirmed by northern blots, quantitative reverse transcription-PCR analyses and in situ hybridization. The overexpression of these four miRs in two human ATC-derived cell lines suggests a critical role of miR-125b and miR-26a downregulation in thyroid carcinogenesis, since a cell growth inhibition was achieved. Conversely, no effect on cell growth was observed after the overexpression of miR-30d and miR-30a-5p in the same cells. In conclusion, these data indicate a miR signature associated with ATC and suggest the miR deregulation as an important event in thyroid cell transformation.
Summary
Background Interstitial granulomatous dermatitis (IGD) is a rare disease for which a clinical–pathological correlation is essential to establish diagnosis.
Objectives To describe the ...histological and clinical features of patients with IGD seen in our department from 2004 to 2010, and to undertake a literature review and critical analysis of additional cases.
Methods Twelve adult patients (nine women and three men; mean age 58·5 years; range 32–73 years) with IGD were enrolled. Lesions consisted of asymptomatic erythematous papules and plaques, symmetrically distributed on the trunk and the proximal limbs. Two patients had skin‐coloured papules. Six patients had articular involvement (arthralgias, spondyloarthritis, rheumatoid arthritis) and three patients had cancer.
Results All cases showed a predominant CD68‐positive macrophage infiltrate distributed between collagen bundles of the mid‐ and deep dermis. Macrophages were also surrounding degenerated collagen fibres. A few neutrophils and/or eosinophils were also present. No vasculitis or significant mucin deposition was observed. Of the 62 cases of IGD reported since 1993, 53 fulfilled stringent diagnostic criteria. Erythematous papules and plaques on the trunk and proximal limbs were the dominant manifestation. Approximately 10% of patients had cord‐like lesions. More than 50% of patients with IGD had arthralgia or arthritis, and less commonly other rheumatic disorders. Disease duration is months to years, but long‐term prognosis seems favourable.
Conclusions IGD is a distinct entity with a typical histological and clinical pattern. The importance and the nature of the association with extracutaneous diseases remains to be clarified. Patients should be screened for rheumatic and autoimmune diseases.
•Monocyte-derived macrophages from 110 goats were challenged with B. melitensis 16 M.•MDMs restrictive or permissive to Brucella intracellular growth were identified.•“Restrictive” macrophages showed ...enhanced phagocytosis in vitro.•A tendency to greater induction of reactive species was observed in these cells.•Natural antibodies did not show any particular distribution between groups.
Caprine brucellosis is a chronic, world-wide distributed disease which causes reproductive failure in goats and Brucella melitensis, its causative agent, bears a great zoonotic potential. There is evidence suggesting that some cattle and pigs have an innate ability to resist Brucella infection, but this has not yet been investigated in goats. In this study, we compared caprine macrophages that exhibit extreme restriction and permissiveness to B. melitensis’ intracellular growth in vitro. Monocyte derived macrophages (MDMs) from 110 female goats were cultured and challenged in vitro with B. melitensis 16 M. After initial screening, 18 donor goats were selected based on their macrophages ability to restrict or allow bacterial intracellular growth and some elements of humoral and cellular immunity were studied in depth. MDMs that were able to restrict the pathogen’s intracellular growth showed enhanced bacterial internalization, although there were no differences between groups in the production of reactive oxygen and nitrogen intermediates following 48 h treatment with heat-killed B. melitensis. Moreover, there were no differences between groups in the level of antibodies reacting with keyhole limpet hemocyanin (natural antibodies, NAbs) or with Brucella LPS antigens (cross-reacting antibodies, CrAbs), although a strong positive correlation between individual levels of IgM NAbs and IgM CrAbs was detected. Altogether, these results represent an initial step in understanding innate primary host response to B. melitensis, and deciphering which mechanisms may determine a successful outcome of the infection in goats.
Summary
Objective Serum thyroglobulin (Tg) represents a highly specific biomarker for detecting residual thyroid tissue/recurrence/metastases after treatment for differentiated thyroid cancer (DTC). ...We evaluated the clinical impact of a highly sensitive Tg assay during routine follow‐up of DTC patients.
Design Tg values were measured by a highly sensitive Tg assay during L‐T4 suppressive therapy and after recombinant human thyrotropin (rh‐TSH) stimulation and were compared with those obtained by using a routinely employed Tg assay.
Patients One hundred and sixty consecutive DTC‐treated patients (papillary carcinoma n = 124, follicular carcinoma n = 36) were studied.
Measurements Measured variables included neck ultrasonography, 131I whole body scanning, and Tg assayed by Immulite (Diagnostic Products Corporation, Los Angeles, CA) and by the highly sensitive Access assay (Beckman Coulter, Brea, CA).
Results During L‐T4 therapy, measurable Tg was found in only two patients (1% of total) by Immulite and in 23 patients (14% of total) by Access assay. Using the institutional cut‐off of 2 µg/l after rh‐TSH, a negative response was associated with undetectable Immulite Tg during L‐T4 therapy in all patients (negative predictive value, NPV, 100%) and in 137 out of 152 patients with Access assay (NPV 90%). Measurable Tg during L‐T4 therapy was found in 17% of positive patients with Immulite and in 100% of patients with Access, respectively.
Conclusions The use of a highly sensitive Tg assay may represent a useful diagnostic tool for improving the interpretation of Tg results during monitoring of DTC‐treated patients for the early detection of recurrence and for optimizing the use of the more expensive rh‐TSH test.
Introduction:
Human leukocyte antigen-G (HLA-G), a nonclassical major histocompatibility complex class I antigen, plays a pivotal role in immune tolerance and a paradoxical role in cancers.
Aims:
Our ...aims were to evaluate plasma soluble HLA-G (sHLA-G) concentrations and the 14-bp insertion/deletion polymorphism of the HLA-G gene in patients with papillary thyroid carcinoma (PTC) or Hashimoto's thyroiditis (HT) and to assess the possible association of these parameters with PTC aggressiveness.
Methods:
Samples for the analysis of sHLA-G and +14/−14-bp HLA-G polymorphism were obtained from 121 patients with HT and 183 with PTC; 245 gender- and age-matched healthy subjects served as controls. PTC histopathological aggressiveness was defined according to the last American Thyroid Association guidelines.
Results:
Positive serum antithyroid antibody titers were observed in 22% of PTC patients and lymphocyte infiltration of thyroid parenchyma at histological examination in 21%, whereas both circulating and histological autoimmunity was detectable in 12% of PTC patients. No differences in the +14/−14-bp polymorphism frequencies were observed between the study groups. The prevalence of detectable sHLA-G was lower in healthy controls (52%) as compared with both HT (57%) and PTC (62%) patients. By stratifying the study groups according to sHLA-G level of positive subjects, significantly higher plasma sHLA-G values in PTC (42.9 ± 3.3 ng/ml; P = 0.002) and HT patients (49.1 ± 2.6 ng/ml; P < 0.002) as compared with healthy controls (8.5 ± 1.8 ng/ml) were obtained. Moreover, PTC patients with detectable plasma sHLA-G levels showed a higher aggressive behavior (P < 0.04) than those without.
Conclusions:
Although confirming the frequent association between PTC and chronic autoimmune thyroiditis, these data suggest that elevated circulating sHLA-G levels, besides an important signal of alterations of immune homeostasis, may be considered a potential, novel marker of PTC histopathological aggressiveness at diagnosis. Additional studies are needed to confirm the actual role and clinical relevance of the HLA-G complex in PTC development and progression.
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