Expression of amoebapores is required for full expression of Entamoeba histolytica virulence in amebic liver abscess but is not necessary for the induction of inflammation or tissue damage in amebic colitis

Entamoeba histolytica trophozoites produce amoebapores, a family of small amphipathic peptides capable of insertion into bacterial or eukaryotic membranes and causing cellular lysis. Recently, E. histolytica trophozoites that are totally deficient in the production of amoebapore-A were created through a gene silencing mechanism (R. Bracha, Y. Nuchamowitz, and D. Mirelman, Eukaryot. Cell 2:295-305, 2003). Here we tested the virulence of amoebapore A(-) trophozoites in models of the two major forms of amebic disease: amebic liver abscess and amebic colitis. We demonstrate that amoebapore expression is required for full virulence in the SCID mouse model of amebic liver abscess, but E. histolytica trophozoites that do not express amoebapore-A can still cause inflammation and tissue damage in infected human colonic xenografts. These data are consistent with the concept that tissue damage may proceed by different mechanisms in amebic liver abscess compared to amebic colitis.     

The great mimicker: Phenotypic overlap between constitutional mismatch repair deficiency and Tuberous Sclerosis complex

Constitutional mismatch repair deficiency is a rare cancer predisposition syndrome caused by biallelic mutations in one of the four mismatch repair genes. Patients are predisposed to various tumors including hematological malignancies, brain tumors and colorectal carcinomas. Phenotypic overlap with Neurofibromatosis-1 is well known, with most patients presenting with café-au-lait macules. Other common features include axillary and/or inguinal freckling and intracranial MRI foci of high T2W/FLAIR signal intensity similar to the typical FASI seen in Neurofibromatosis-1. In this cohort of eight patients with constitutional mismatch repair deficiency we describe overlapping phenotypical features with Tuberous Sclerosis complex. In addition to “ash-leaf like” hypomelanotic macules (five patients), we detected intracranial tuber-like lesions (three patients), renal cysts (three patients) and renal angiomyolipomas (two patients). All our patients also had Neurofibromatosis-1 like features, mainly café-au-lait macules. This study suggests that features of Tuberous sclerosis especially when overlapping with those of Neurofibromatosis 1 or malignancies atypical for these syndromes should raise the possibility of constitutional mismatch repair deficiency. Correct diagnosis is essential for appropriate genetic counseling and pre-emptive cancer surveillance.     

Purification and characterization of placental heparanase and its expression by cultured cytotrophoblasts

The role of different extracellular matrix (ECM)-degrading enzymesin the normal functioning of the placenta is well documented.Heparan sulphate proteoglycan (HSPG) is an integral constituentof the placental and decidual ECM. Because this proteoglycanspecifically interacts with various macromolecules in the ECM,its degradation may disassemble the matrix. Hence, in the caseof the placenta, this may facilitate normal placentation andtrophoblast invasion. Crude placental specimens were collectedfrom first and third trimester placentas. Heparanase (endo-P-glucuronidase)was isolated and purified by ammonium sulphate precipitationfollowed by sequential chromatographies on carboxymethyl-, heparin-and ConA-Sepharose columns. The placental enzyme was furthercharacterized for its molecular weight and specific inhibitionby heparin, and was shown to resemble heparanase expressed byhighly metastatic tumour cells and activated cells of the immunesystem. In order to locate the source of heparanase activityin the placenta, primary cytotrophoblast cultures were established.Intact cells, as well as conditioned medium and cell lysates,were analysed for heparanase activity using metabolically sulphate-labelledECM as a natural substrate. Heparanase was highly active inlysates of cytotrophoblasts. This activity was also expressedby intact cytotrophoblasts seeded on ECM, but no activity couldbe detected in the culture medium. Incubation of the cytotrophoblastsin contact with ECM resulted in release of ECM-bound basic fibroblastgrowth factor (bFGF). We propose that the cytotrophoblasticheparanase facilitates placentation, through cytotrophoblastextravasation and localized neovascularization. cytotrophoblast/extracellular matrix/heparanase/heparan sulphate proteoglycan/placenta     

Duplication of distal 22q

We report on three patients with duplication of distal 22q. One patient is a de novo carrier of the translocation t(21;22) (p13;q11), the other two are offspring of a translocation carrier t(10;22) (q26;q12). The clinical manifestations of these patients demonstrate the variability of the dup(22q) syndrome.     

A de novo translocation, 14q21q,with a microchromosome—14p21p

A familial translocation, t(14;21)(14p21p;14q21q), in a mother and her child is described. The translocation was ascertained through the birth of a Down syndrome baby with the chromosome constitution 47,XX,-14, +der 14, +der 21,t(14;21)(q11; p12) mat. A 1:3 segregation in the maternal meiosis is suggested for the evolution of the unbalanced chromosome state. The main translocated chromosome 14q21q mimics the product of a Robertsonian translocation, while the 14p21p chromosome has the morphology of a satellited microchromosome. The cytogenetic nature of this translocation is discussed.     

Cytokeratin polypeptide expression in a cloacogenic carcinoma and in the normal anal canal epithelium

Summary The aim of the present study was to explore the origin of cloacogenic carcinoma in the anal canal by immunohistochemical methods. We compared cytokeratin polypeptide expression of a cloacogenic carcinoma to normal anal epithelia, to anal squamous cell carcinoma and to basal and squamous cell carcinoma of the skin, using a battery of monoclonal anti-cytokeratin, polypeptide-specific antibodies. Our results indicate that cloacogenic carcinoma expresses cytokeratin polypeptides similar to those of the basal layer of anal squamous epithelium, of the anal transitional zone epithelium and of a layer of basal cells in the anal glands. Thus we concluded that each of the above cell types may be the cell of origin of cloacogenic carcinoma.     

Are cognitive–behavioral interventions effective in reducing occupational stress among nurses?

Despite the growing evidence regarding the effectiveness of cognitive–behavioral interventions in reducing occupational stress, very few studies have examined its effectiveness among nurses. This study investigated the impact of a cognitive–behavioral (CB) course on the nurses' well-being. The study compared the sense of coherence (SOC), perceived stress (PSS), and mood states of 20 nurses who had participated in the CB course to that of 16 control participants using a pre–post test design. At baseline (t1), no significant differences were found between the two groups in SOC, PSS, and mood states. The effects within each group controlling for t1 were examined by analysis of covariance. At t2, a significant increase in SOC and the mood state of vigor and a significant decrease in PSS and fatigue were found only among participants in the CB course. The results are discussed in relation to the conceptual framework of stress and coping theory.