Clear-cell myoepithelial carcinoma of the salivary glands: a clinicopathologic, immunohistochemical, and ultrastructural study of two cases involving the submandibular gland with review of the literature

Myoepithelial carcinoma (MC) is an uncommon neoplasm of the salivary glands, and cases of the clear-cell (CC) variant are extremely rare. Two cases of MC of the CC variant arising in the left submandibular gland are described herein. Both cases, which involved elderly women, almost exclusively consisted of large glycogen-rich CCs. Both cases were immunopositive for several epithelial and myoepithelial markers, and electron microscopy (EM) demonstrated hybrid epithelial and myoid differentiation in both. Case 1 arose in a pre-existing pleomorphic adenoma ("ex mixed tumor MC"), while Case 2 was a "de novo MC". CC-MC is an aggressive tumor with frequent recurrence, lymph node, and systemic metastases. A total of 14 cases of this type of neoplasm have been reported so far in the salivary glands, two arising from the submandibular gland. To date, only four cases have been studied using EM. The cases of CC-MC presented here are the third and fourth ones, respectively, originating from the submandibular glands, and the first two cases arising from this location, in which EM investigation succeeded in demonstrating myoepithelial differentiation. CC-MC needs to be distinguished from diverse primary and secondary CC neoplasms.     

Extracellular survivin up-regulates adhesion molecules on the surface of leukocytes changing their reactivity pattern

Rheumatoid arthritis (RA) is an autoimmune disease with joints as a principal target of inflammation. We have shown recently that the extracellular expression of the antiapoptotic protein survivin is associated with a destructive course of RA. Here, we address the potential impact of extracellular survivin on peripheral blood leukocytes (PBL). The binding of survivin to the surface of human PBL as well as the expression of adhesion molecules were assessed by FACS. The expression of adhesion molecules on leukocytes as a function of circulating survivin was analyzed in blood of 24 patients with RA and compared with eight healthy individuals. We show that extracellular survivin expresses immunomodulatory properties. It binds to the surface of the majority of granulocytes and a significant part of lymphocytes and monocytes inducing the activation of alpha-chains of beta-integrins and their ligand ICAM-1. Survivin-induced expression of alpha-chains of beta 2-integrins is regulated by p38 MAPK and PI-3K but not by the NF-kappaB signaling pathway. Clinical relevance of our findings is supported by the in vivo association of high circulating survivin levels with an increased expression of CD11c on monocytes and granulocytes in RA patients. The results of our study demonstrate that extracellular survivin affects the phenotype of leukocytes having a possible impact on homing of inflammatory cells during arthritis.     

B-cell non-Hodgkin lymphomas in Uganda: an immunohistochemical appraisal on tissue microarray

The most common non-Hodgkin lymphomas in Uganda are neoplasms of B-cell derivation. The field of B-cell lymphoma immunophenotype has rapidly progressed because of the increasing availability of markers applicable to routine sections. Although the latter have allowed the identification of distinctive lymphoma entities in the developed countries, such approach has not yet been used in Uganda. One hundred twenty-nine formalin-fixed, paraffin-embedded tissue samples from the Department of Pathology of Makerere University were used for tissue micro-array (TMA) construction. Four-micrometer-thick sections were cut from TMAs and stained with hematoxylin and eosin and Giemsa. They were also used for immunohistochemistry and in situ hybridization. According to morphology and immunohistochemistry, lymphoid neoplasms were classified as Burkitt's lymphoma (BL) (95 cases), diffuse large B-cell lymphoma (19 cases), mantle cell lymphoma (4 cases), and B-cell lymphoblastic lymphoma (1 case). In BL, a homogeneous phenotype (CD10(+), Bcl-6(+), Bcl-2(-), MUM1/IRF4-, and Ki-67 approximately 100%) and a stable Epstein-Barr virus integration were found. A distinctive and unusual feature was the frequent plasma cellular differentiation, along with the positivity for CD30 and CD138 (recorded in 35 and 43 cases, respectively). According to our findings, most non-Hodgkin B-cell tumors in Uganda are endemic BLs followed by diffuse large B-cell lymphomas. The rest consist of rare but clinically important entities such as mantle cell lymphoma and B-cell lymphoblastic lymphoma. The availability of TMAs and immunohistochemistry has enabled us to precisely categorize tumors that have so far been diagnosed in Uganda as "high-grade/aggressive" lymphomas on the basis of cell morphology alone.     

Transitional cell carcinoma of the endometrium and endometrial carcinoma with transitional cell differentiation: a clinicopathologic study of 5 cases and review of the literature

To date, only 16 cases of transitional cell carcinoma of the endometrium and endometrial carcinoma with transitional cell differentiation have been reported in the literature. We reviewed the clinicopathologic features of 5 cases of endometrial carcinoma with transitional cell differentiation. The mean age was 68 years, and all patients presented with postmenopausal bleeding. Macroscopically, the tumors were intracavitary and friable. Microscopically, the tumors were composed of tightly packed papillary structures with thin fibrovascular cores, resembling a transitional cell carcinoma of the urinary tract. One tumor showed exclusively transitional cell differentiation, whereas the remaining 4 neoplasms showed that the transitional cell carcinoma was admixed with a variable proportions of endometrioid adenocarcinoma. Four cases were in FIGO stage IB, whereas the remaining tumor infiltrated the uterine cervix (FIGO stage IIB). Immunoreactivity was typical of müllerian derivatives (cytokeratin 7 positive, cytokeratin 20 negative). p16 protein was positive in all cases, but human papillomavirus DNA was not detected in any of the tumors. None of the patients developed local recurrence or distant metastases, even though there are too few cases of transitional cell carcinoma of the endometrium reported to make any statistically valid conclusions about response to therapy and prognosis. Transitional cell carcinoma is an unusual variant of endometrial carcinoma, with distinctive histologic and immunophenotypic features. Identification of this variant broadens the morphological spectrum of epithelial neoplasms of the endometrium.     

Combination of biomarkers to predict mortality in elderly patients with myocardial infarction

OBJECTIVE: The elderly subjects affected by Acute Myocardial Infarction (AMI) have the highest risk of mortality. Our study was designed to improve the capability of mortality risk stratification in elderly AMI patients through the concurrent evaluations of different biomarkers, including genetic markers. METHODS AND RESULTS: One-year follow-up study was performed in 250 elderly AMI patients. The combination of high total Homocysteine (tHcy), low folate and vitamin B12 plasma levels (18.0+/-9.0 micromol/l; 4.4+/-1.2 ng/ml; 404.2+/-287.5 pg/ml, respectively) and elevated CRP plasma levels (> or =6 mg/dl) identify the highest-risk pathway of heart mortality (RR=4.20, IC 95% 1.62-10.89, P<0.002) with respect to the combination of low total tHcy, high folate and vitamin B12 plasma levels (12.4+/-5.2 micromol/l; 8.9+/-2.5 ng/ml; 546.9+/-379.8 pg/ml, respectively) and low CRP plasma levels (<6 mg/dl). CONCLUSION: In elderly AMI patients the concomitant elevation of CRP and tHcy, associated with folate and vitamin B12 low levels, could be considered a significant predictive heart mortality risk factor.     

Lovastatin induces apoptosis of k-ras-transformed thyroid cells via inhibition of ras farnesylation and by modulating redox state

Transformation of thyroid cells with either K-ras or H-ras viral oncogenes produces cell types with different phenotype and different response to the inhibition of the prenylation pathway by 3-hydroxy-3-methylglutaryl-CoA reductase or farnesyltransferase inhibitors. These inhibitors induce apoptosis in K-ras-transformed FRTL-5 cells (FRTL-5-K-Ras) whereas cell cycle arrest is induced in H-ras-transformed FRTL-5 (FRTL-5-H-Ras). In FRTL-5-K-Ras cells, the product of K-ras gene is implicated in the scavenging of reactive oxygen species (ROS) through the activation of extracellular-signal-regulated kinase (ERK)1/2 kinases. We observed that lovastatin blocked ras activation through inhibition of farnesylation and induced apoptosis, increasing ROS levels through inhibition of ERK1/2 signaling and Mn-SOD expression. Lovastatin-induced apoptosis was due to intracellular ROS increase since both, the antioxidant compound pyrrolidinedithiocarbamate or the SOD-mimetic compound, antagonized apoptosis. Moreover, both p38 mitogen-activated protein kinase and nuclear factor κB pathways, activated as a consequence of high ROS levels, are involved in the apoptotic effect, indicating that cell death induced by lovastatin was dependent on oxidative stress. Lovastatin antitumor efficacy in K-ras-dependent thyroid tumors was further confirmed in vivo, proposing a new therapeutic strategy for those tumor diseases that are sustained by an inappropriate K-ras expression. C.L. and L.F. contributed equally to this work.     

Proton pump inhibitors prescribing following the introduction of generic drugs

Eur J Clin Invest 2012; 42 (10): 1068-1078 ABSTRACT: Background In many countries, the introduction of generic proton pump inhibitors (PPIs) onto the pharmaceutical market increased the phenomenon of therapeutic substitution in acid-related disorders (ARDs). Aim To investigate the treatment of ARDs in an Italian primary care setting from 2005 to 2008 by verifying: (i) dynamics of PPI prescribing; (ii) predictors of PPI switching; and (iii) healthcare resource consumption costs. Methods This was a retrospective cohort study of 102 general practitioners (GPs) who managed an average of 150?000 inhabitants in Naples. Multilevel logistic regression was used to assess the potential predictors of both PPI switching and termination. Primary care costs were expressed as the cost of ARD management per PPI user year. Results The percentage of PPI users with ARD increased from 5·5% (2005) to 7·0% (2008) (P?相似文献   

Intra- and interoperator reproducibility of acoustic radiation force impulse (ARFI) elastography--preliminary results

Our study assessed acoustic radiation force impulse (ARFI) reproducibility and the factors influencing it. The intra- and interoperator reproducibility were studied in 33 and 58 patients, respectively. Intraclass correlation coefficient (ICC) was used to assess ARFI reproducibility. The overall intraoperator agreement was better than the interoperator one: ICC 0.90 vs. ICC 0.81. The correlation of repeated ARFI measurements was higher, but not significantly so, in cases in which intraoperator reproducibility was assessed compared with the ones in which interoperator reproducibility was studied: r = 0.848 vs. r = 0.694 (p = 0.08). For both intra- and interoperator reproducibility, the ICCs were smaller in women vs. men (0.88 vs. 0.91 and 0.67 vs. 0.86, respectively), in patients with high body mass index (BMI) ≥25 kg/m2 vs. <25 kg/m2 (0.88 vs. 0.91 and 0.79 vs. 0.82, respectively), in patients with ascites vs. no ascites (0.80 vs. 0.93 and 0.78 vs. 0.84, respectively) and in noncirrhotic vs. cirrhotic patients (0.77 vs. 0.82 and 0.70 vs. 0.83, respectively).     

Oxygen tension and formation of cervical-like tissue in two-dimensional and three-dimensional culture

Cervical dysfunction contributes to a significant number of preterm births and is a common cause of morbidity and mortality in newborn infants. Cervical dysfunction is related to weakened load bearing properties of the collagen-rich cervical stroma. However, the mechanisms responsible for cervical collagen changes during pregnancy are not well defined. It is known that blood flow and oxygen tension significantly increase in reproductive tissues during pregnancy. To examine the effect of oxygen tension, a key mediator of tissue homeostasis, on the formation of cervical-like tissue in vitro, we grew primary human cervical cells in both two-dimensional (2D) and three-dimensional (3D) culture systems at 5% and 20% oxygen. Immunofluorescence studies revealed a stable fibroblast phenotype across six passages in all subjects studied (n=5). In 2D culture for 2 weeks, 20% oxygen was associated with significantly increased collagen gene expression (p<0.01), increased tissue wet weight (p<0.01), and increased collagen concentration (p=0.046). 3D cultures could be followed for significantly longer time frames than 2D cultures (12 weeks vs. 2 weeks). In contrast to 2D cultures, 20% oxygen in 3D cultures was associated with decreased collagen concentration (p<0.01) and unchanged collagen gene expression, which is similar to cervical collagen changes seen during pregnancy. We infer that 3D culture is more relevant for studying cervical collagen changes in vitro. The data suggest that increased oxygen tension may be related to significant cervical collagen changes seen in pregnancy.