Three-state opinion model with mobile agents.

We study an agent-based opinion model with two extreme (opposite) opinion states and a neutral intermediate one. We adjust the relative degree of conviction between extremists and neutrals through a dimensionless parameter called the "neutrality parameter" to investigate its impact on the outcome of the system. In our model, agents move randomly on a plane with periodic boundary conditions and interact with each other only when they are within a fixed distance threshold. We examine different movement mechanisms and their interplay with the neutrality parameter. Our results show that in general, mobility promotes the global consensus, especially for extreme opinions. However, it takes significantly less time to reach a consensus on the neutral opinion.

Vitamin D receptor expression and acid sphingomyelinase activity in prefrontal region of a learning animal model.

Contextual fear conditioning (CFC) paradigm is routinely used to study fear-based learning in animals and it provides a useful model for understanding fear and anxiety in human. In the present study, such model was used following the previously established CFC protocol, and immunohistochemistry, enzymatic activity and western blotting analysis approaches were used to identify the expression of acid sphingomyelinase (aSMase) and vitamin D receptor (VDR) in prefrontal region brain of rat. Results revealed an increase of aSMase activity in conditioned rats, suggesting an apoptotic condition in such animals. In addition, an increase of density and organization of axonal neurofilaments and of VDR expression has been observed in brain of conditioned rats, supporting an induction of growth and organization of new neurons in prefrontal regions, whose contribution to various aspects of contextual fear learning is still largely unknown.

Reinterpretation of mouse thyroid changes under space conditions: the contribution of confinement to damage.

During space missions, astronauts work in a state of separation from their daily social environment and in physical confinement. It has been shown that confinement influences mood and brain cortical activity, but no data has been obtained with regard to its effect on the thyroid gland, the structure and function of which change during spaceflights. Here, we report the results of a study on the effects of confinement on mouse thyroid, which was implemented with the Mice Drawer System Facility maintained on the ground, a system used for spaceflight experiments. The results show that confinement changes the microscopic structure of the thyroid gland and that it exhibits symptoms similar to those that result from physiological and/or pathological hyperfunction. What is left unchanged, however, is the sphingomyelinase-thyrotropin receptor relationship, which is important for thyrotropin response with a consequential production of hormones that act on the metabolism of almost all tissues and reduces the production of calcitonin, a hormone involved in bone metabolism. During space missions, the overexpression of pleiotrophin, a widespread cytokine up-regulated after tissue injury that acts on bone remodeling, attenuates changes to the thyroid that are spaceflight-dependent; therefore we studied the thyroids of pleiotrophin-transgenic mice in the Mice Drawer System Facility. In confinement, pleiotrophin overexpression does not protect from the loss of calcitonin. The contribution of confinement to thyroid damage during spaceflights is discussed.

Observing the mouse thyroid sphingomyelin under space conditions: a case study from the MDS mission in comparison with hypergravity conditions.

This is a case report of apparent thyroid structural and functional alteration in a single mouse subjected to low Earth orbit spaceflight for 91 days. Histological examination of the thyroid gland revealed an increase in the average follicle size compared to that of three control animals and three animals exposed to hypergravity (2g) conditions. Immunoblotting analysis detected an increase in two thyroid gland enzymes, sphingomyelinase and sphingomyelin-synthase1. In addition, sphingomyelinase, an enzyme confined to the cell nucleus in the control animals, was found in the mouse exposed to hypogravity to be homogeneously distributed throughout the cell bodies. It represents the first animal observation of the influence of weightlessness on sphingomyelin metabolism.

The thyroid lobes: the different twins.

Although differences in size of the right and left thyroid lobes are well defined, differences in morphology, follicles structure, cAMP production, thyrotropin receptor, and protein involved in cell signalling have not previously been reported. This study provides morpho-functional data of right and left thyroid lobes by biochemical, immunohistochemistry, immunoblotting and immunofluorescence analysis. We demonstrate that, in comparison with the left lobe, the right lobe has a higher activation index, is more sensitive to thyrotropin treatment, is rich in thyrotropin receptor and caveolin 1 involved in thyroid hormone synthesis as well as in epithelial thyroid cell homeostasis, is characterised by a high content of molecules involved in cell signalling such as stat3, raf1, sphingomyelinase and sphingomyelin-synthase whose activity ratio is necessary for epithelial cell activity and finally has more areas calcitonin-dependent. The relation between structure/function of right lobe and its susceptibility to the higher risk of pathological modifications with respect the left lobe is discussed.

EGFR, pMAPK, pAkt and PTEN status by immunohistochemistry: correlation with clinical outcome in HER2-positive metastatic breast cancer patients treated with trastuzumab.

BACKGROUND: In an attempt to identify markers of resistance to trastuzumab, we evaluated both the profiling of human epidermal growth factor receptor 2 (HER2)-positive tumor cells measuring the relative levels of EGFR, pMAPK, pAkt and PTEN and their correlations with clinical outcome in HER2-positive metastatic breast cancer patients treated with trastuzumab. PATIENTS AND METHODS: Tumor tissues for this retrospective analysis were available from 45 out of 76 patients with metastatic breast cancer treated from April 1999 to March 2006 with trastuzumab-based therapy at our Institution. Evaluations of EGFR, pMAPK, pAkt and PTEN status by immunohistochemistry (IHC) were carried out on all 45 tissue samples and their correlations with response to trastuzumab, incidence of central nervous system (CNS) metastases, time to progression (TTP), overall survival from diagnosis of breast cancer (OS1), from diagnosis of metastatic disease (OS2) and from the start of trastuzumab (OS3) were analyzed. RESULTS: We observed that TTP (P = 0.001) and median OS2 and OS3 were significantly longer in patients responsive to trastuzumab-based regimen compared with nonresponsive patients. EGFR, pMAPK, pAkt and PTEN status by IHC were not significantly associated with response to trastuzumab, TTP, overall survival (OS1, OS2, OS3) and CNS metastases incidence. A trend for shorter OS3 was observed for pMAPK-positive patients compared with pMAPK-negative patients (22.8 versus 31.2 months; P = 0.076). Median OS1 resulted shorter in 22 pAkt-positive patients (69.8 months) compared with 23 pAkt-negative patients (108.2 months); P = 0.091. It is likely that high expression of pMAPK (pMAPK-positive status) or pAkt (pAkt-positive status) could identify a subgroup of HER2-positive tumors with high activity of proliferation and survival pathways and with resistance to trastuzumab. CONCLUSIONS: In HER2-positive metastatic breast cancers, EGFR, pMAPK, pAkt and PTEN status evaluated by IHC was not significantly associated with response to trastuzumab, TTP, OS and CNS metastases incidence. However, HER2 status determined by IHC and/or FISH assays may not be sufficient to predict response to trastuzumab-based therapy.

Computer-assisted immunocytochemical determination of breast cancer steroid receptors. Frozen sections vs paraffin sections.

Previously we have demonstrated that determination of oestrogen (ER) and progesterone (PR) receptors by immunocytochemical assay (ICA) on frozen sections (FS) and cytological smears with image analysis is effective for evaluating steroid receptors. The aim of this study was to determine concordance between ER and PR assessed by ICA on FS and paraffin sections (PS) both evaluated by image analysis. There were 115 breast carcinomas selected. For all cases, ER and PR determination was performed on FS and PS. Computer-assisted image analysis was performed using CAS 200. Results were expressed as percent positive area of neoplastic nuclei compared with total nuclear area of the examined neoplastic cells. Good correlation was demonstrated for both ER (r=0.759; concordance=83.4%) and PR (r=0.800; concordance=87.8%). The unexpected relatively low concordance for ER led to further investigations. We divided the 115 cases in two groups. The first group included specimens from our hospital; the second group specimens from suburban hospitals. In the first group there was better correlation for both ER (r=0.897) and PR (r=0.915) with a concordance of 91.5% and 93.6%, respectively. In the second group, correlation was worse for both ER (r=0.724) and PR (r=0.708), with a concordance of 77.9% and 83.9% respectively. From analysis of discordant cases we conclude that reduction in correlation and concordance with increased false negative cases in group 2 are probably due to delayed fixation. Our data suggest that ICA with automated image analysis is efficient in evaluating ER and PR on paraffin section only when the tumour samples are correctly fixed.

Computer-assisted immunocytochemical determination of breast cancer steroid receptors on cytological smears of excised surgical specimens compared with frozen sections.

BACKGROUND: Due to the widespread use of fine needle aspirate biopsy the practice of determining estrogen (ER) and progesterone (PR) receptors in breast carcinoma from cytological smears (CS) is becoming very common. The aim of this study was to determine concordance between ER and PR assessed by immunocytochemical assay (ICA) on CS and FS both evaluated by image analysis since we have found no data in literature on this. METHODS: 104 breast carcinoma cases were selected. For all cases ER and PR determination was performed on CS, obtained by light scraping of the freshly cut surface of the excised surgical tumors at the time of frozen section diagnosis, and FS using the same monoclonal antibodies. Computer-assisted image analysis was performed in all cases using CAS 200. Results were expressed as percent positive area of neoplastic nuclei compared with total nuclear area of the examined neoplastic cells. RESULTS: Good correlation was demonstrated between percent positive nuclear neoplastic area by ER-ICA on CS and FS (r = 0.759; P < 0.0001). Concordance of results was 90.19% (P < 0.001). Good correlation was also demonstrated between percent positive nuclear neoplastic area by PR-ICA in CS and FS (r = 0.889; P < 0. 0001). Concordance of results was 97.02% (P < 0.0001). CONCLUSIONS: Our data suggest that ICA on CS with automated image analysis is efficient in evaluating ER and PR content in human breast cancer, especially when CS is the only method pathologists have to evaluate receptor status e.g. in advanced breast cancer cases when neoadjuvant therapy is necessary before surgery or when surgery is impossible.

Value of c-erbB-2 and p53 oncoprotein co-overexpression in human breast cancer.

p53 and c-erbB-2 protein expression was immunohistochemically examined in a consecutive series of 49 primary breast cancer patients with a 10-year follow-up. The study was performed on paraffin sections using the monoclonal antibodies DO7 and CBE1; the former recognizes both the wild-type and the mutant p53 forms, the latter recognizes the external domain of the transmembrane c-erbB-2 protein. Positive staining was expressed in 12.2% and 16.3% of cases for p53 and c-erbB-2 proteins, respectively. The results were related to clinicopathological parameters by the chi 2 test. A significant correlation was found between positive c-erbB-2 immunostaining and poor survival (P = 0.04) and between p53 and c-erbB-2 overexpression (P = 0.003); this co-overexpression correlated well with a poor clinical outcome (P = 0.040). From our results, we may speculate that simultaneous expression of p53 and c-erbB-2 oncoproteins could be a critical event in breast tumor progression, and therefore, of prognostic value to identify patients at high risk.

Combined overexpression of urokinase, urokinase receptor, and plasminogen activator inhibitor-1 is associated with breast cancer progression: an immunohistochemical comparison of normal, benign, and malignant breast tissues.

BACKGROUND: A strong positive correlation exists between the breast cancer tissue content of either urokinase-plasminogen activator (uPA) or plasminogen activator, inhibitor type I (PAI-1), quantified in the tissue extracts by immunoassays, and the survival of patients with breast cancer. Furthermore, several studies assign to the urokinase-type plasminogen activator receptor (uPAR) a pivotal role in triggering the proteolytic activity of the urokinase pathway involved in tumor stroma degradation, tumor spread and metastasis. However, the pattern of distribution of uPAR in normal and cancerous human tissue and the pattern of coexpression of activators and inhibitors that occurs in breast cancer tissues is not completely known. METHODS: The immunohistochemical localization of uPAR, uPA, tPA) and PAI-1 was evaluated by using the avidin-biotin immunoperoxidase technique and affinity-purified monoclonal antibodies from American Diagnostica Inc. Studies were performed in formalin fixed, paraffin-embedded tissue prepared from 23 surgically excised non-neoplastic breast tissues and 18 ductal breast carcinomas. RESULTS: While the expression of uPAR protein represents a constant feature of invasive ductal breast cancer, it was also observed in most of the breast tissue samples, including the normal breast tissues. The staining for uPAR was mainly localized on normal or tumoral epithelial cells, even if the co-expression of uPAR in stromal cells was frequently observed in adjacent slides. A semiquantitative analysis of immunohistochemical results showed that uPAR and PAI-1 were overexpressed in invasive breast cancer in comparison with normal and benign breast tissues. In addition, uPA was higher in both invasive breast carcinomas and benign breast lesions with respect to normal breast tissues. CONCLUSIONS: We showed that overexpression of uPAR, uPA, and its main inhibitor, PAI-1, is a constant feature of invasive ductal breast carcinomas. However, the expression of the above fibrinolytic reactants is not specific for breast cancer since positive staining for these molecules was frequently observed in benign breast lesions as well as in normal breast tissues. The combined increased expression of uPA and its cellular receptor, uPAR on the surface of tumor epithelial cells may account for the activation of the proteolytic system which occurs in breast cancer.

Granular cell tumor: an immunohistochemical study.

AIMS AND BACKGROUND: Granular cell tumor, usually a benign neoplasm, has been the object of many studies because of its uncertain histogenesis and based on many immunohistochemical and ultrastructural studies it has been suggested that it originates from the Schwann cell. Our recent observation that granular cell tumor is positive with PG-M1, a new anti-macrophage monoclonal antibody, led us to further investigate the immunophenotypic profile of the tumor. STUDY DESIGN: We studied 11 granular cell tumors using a panel of 20 antibodies, 13 monoclonal and 7 polyclonal. RESULTS: The immunohistochemical study showed in all cases a constant diffuse positivity for S-100 protein, neuron-specific enolase, vimentin, KP1 and PG-M1, as well as occasional and focal positivity for alpha-1-antitrypsin, alpha-1-antichymotrypsin and lysozyme. CONCLUSIONS: The immunophenotypic profile constantly observed could be the expression, on one hand, of the neuroectodermic nature of the neoplasm, proven by positivity for S-100 protein, neuron specific enolase and vimentin, and on the other could be the expression of the phagocytic activity of the tumor cell, proven by positivity for KP1 and PG-M1 antibodies and also by the presence of numerous phagolysosomes.

Changing patterns in gastric carcinoma.

In order to document any modifications in age and sex distributions, tumor locations and histological types, a retrospective study was performed comparing 377 consecutive cases of gastric cancers observed from 1942 to 1956 with 359 cases diagnosed from 1986 to 1987. The mean age at diagnosis rose from 57 to 66 years with no significant male/female ratio variations (1.6 vs 1.7). Tumors located in the proximal stomach increased from 13 to 23% (p less than 0.001) whereas those arising in the distal stomach decreased from 66 to 50% (p less than 0.001). Intestinal type gastric carcinoma decreased from 65.6 to 52.6% (p less than 0.001). The diffuse type rose from 24 to 43% (p less than 0.001) and the mucoid type fell from 10.3 to 4.4% (p less than 0.001). In spite of the overall decline in intestinal type carcinomas, this form remained more common in the upper third area and increased from 55 to 70% (p less than 0.001). Significant modifications in the distribution of diffuse, mucoid and signet ring cell type carcinomas were also noted. The possible significance and implications of these observations are discussed.