Cerebrovascular disorders in the prenatal period

Fetal stroke can occur between the 14th week of pregnancy and the beginning of labor. The incidence is approximately 17-35 of 100,000 live births. Risk factors are correlated to the mother, the pregnancy, or the factors associated with the fetus itself. Computerized tomography and magnetic resonance imaging are the most commonly used imaging techniques. The authors studied 3 cases with neurological symptoms by magnetic resonance imaging and magnetic resonance-angiography. In these cases, the authors found massive involvement of the left hemisphere that was presumptively correlated with the persistence of the oval foramen. Magnetic resonance-angiography showed a flow reduction in the left cerebral vessels, and in 1 case, there was also persistence of the fetal primitive trigeminal artery. The discrepancy between the extent of the cerebral lesions and the neurological symptoms is associated with cerebral plasticity, which is greater in damage occurring early in fetal life.     

DnIKK2-transfected dendritic cells induce a novel population of inducible nitric oxide synthase-expressing CD4+CD25- cells with tolerogenic properties

BACKGROUND: We previously documented that rat bone marrow-derived dendritic cells (DCs), transfected with an adenovirus encoding a dominant negative form of IKK2 (dnIKK2), have impaired allostimulatory capacity and generate CD4 T cells with regulatory function. Here we investigate the potency, the phenotype, and the mechanism of action of dnIKK2-DC-induced regulatory cells and we evaluated their tolerogenic properties in vivo. METHODS: Brown Norway (BN) transfected dnIKK2-DCs were cultured with Lewis (LW) lymphocytes in primary mixed lymphocyte reaction (MLR). CD4 T cells were purified from primary MLR and incubated in secondary coculture MLR with LW lymphocytes. Phenotypic characterization was performed by fluorescence-activated cell sorting and real-time polymerase chain reaction. The tolerogenic potential of CD4 T cells pre-exposed to dnIKK2-DCs was evaluated in vivo in a model of kidney allotransplantation. RESULTS: CD4 T cells pre-exposed to dnIKK2-DCs were CD4CD25 and expressed interleukin (IL)-10, transforming growth factor-beta, interferon-gamma, IL-2, and inducible nitric oxide synthase (iNOS). These cells (dnIKK2-Treg), cocultured (at up to 1:10 ratio) with a primary MLR, suppressed T-cell proliferation to alloantigens. The regulatory effect was cell-to-cell contact-independent since it was also observed in a transwell system. A nitric oxide synthase inhibitor significantly reverted dnIKK2-Treg-mediated suppression, whereas neutralizing antibodies to IL-10 and TGF-beta had no significant effect. DnIKK2-Treg given in vivo to LW rats prolonged the survival of a kidney allograft from BN rats (the donor rat strain used for generating DCs). CONCLUSIONS: DnIKK2-Treg is a unique population of CD4CD25 T cells expressing high levels of iNOS. These cells potently inhibit T-cell response in vitro and induce prolongation of kidney allograft survival in vivo.     

Deregulated overexpression of hCdt1 and hCdc6 promotes malignant behavior

The accurate execution of DNA replication requires a strict control of the replication licensing factors hCdt1 and hCdc6. The role of these key replication molecules in carcinogenesis has not been clarified. To examine how early during cancer development deregulation of these factors occurs, we investigated their status in epithelial lesions covering progressive stages of hyperplasia, dysplasia, and full malignancy, mostly from the same patients. Abnormal accumulation of both proteins occurred early from the stage of dysplasia. A frequent cause of unregulated hCdc6 and hCdt1 expression was gene amplification, suggesting that these components can play a role per se in cancer development. Overexpression of hCdt1 and hCdc6 promoted rereplication and generated a DNA damage response, which activated the antitumor barriers of senescence and apoptosis. Generating an inducible hCdt1 cellular system, we observed that continuous stimulus by deregulated hCdt1 led to abrogation of the antitumor barriers and resulted in the selection of clones with more aggressive properties. In addition, stable expression of hCdc6 and hCdt1 in premalignant papilloma cells led to transformation of the cells that produced tumors upon injection into nude mice depicting the oncogenic potential of their deregulation.     

Lymphoscintigraphic localization of sentinel node in early colorectal cancer: results of a monocentric study

BACKGROUND AND OBJECTIVES: Evaluation of the feasibility of the sentinel node technique in early colorectal neoplasms and its overall accuracy in predicting nodal metastases. METHODS: Thirty-five patients with colon or rectal lesions or degenerate polyps not radically excised by endoscopy were included. Lymphatic mapping was performed with 99mTc labeled albumin colloid injected submucosally by an endoscopic route the afternoon before the surgical procedure. The day of the intervention, 2.5% patent blue V dye (S.A.L.F: Italy) was injected circumferentially around the tumor. A hand held gamma detecting probe (Scintiprobe m100, Pol-Hi-Tech, Italy) was employed to detect "hot" nodes, in vivo and ex vivo. All sentinel nodes were embedded separately for haematoxylin and eosin staining. No IHC or PCR techniques were employed. RESULTS: Sentinel lymph nodes (SLN) were successfully identified in 35 out of 35 patients. Concordance between SLN and nodal status was observed in 32 out of 35 cases (91.4%); four patients (11.4%) were upstaged. Three skip nodal metastases were observed (false-negative rate: 8.5%). CONCLUSIONS: The sentinel node technique with blue dye and radiotracer seems valuable in early colorectal cancers detected by screening programs: a good organization and a learning curve are needed, as further multicentric studies.     

Mutations of the Apc gene in experimental colorectal carcinogenesis induced by azoxymethane in F344 rats.

We investigated in the rat the role of the Apc gene, which is mutated in familial adenomatous polyposis and sporadic colon cancer in the process leading from normal colonic mucosa to aberrant crypt foci (ACF) and finally to adenomas and adenocarcinomas. We analysed mutations in exon 15 of the rat Apc gene using in vitro synthesized protein assay in 66 ACF and in 28 colon tumours induced by azoxymethane. No Apc mutations were found in ACF, whereas five mutations were found in the tumours. The data suggest that mutations of the Apc gene are associated with the transition from ACF to adenoma and adenocarcinoma and not from normal mucosa to ACF.     

Clinico-pathologic correlations of myofibroblastic tumors of the oral cavity. II. Myofibroma and myofibromatosis of the oral soft tissues

BACKGROUND: Myofibroma is a solitary benign tumor of myofibroblasts. Myofibromatosis describes multiple, simultaneous myofibromas at different sites in various organs. The clinico-pathologic correlations of myofibroma/myofibromatosis confined only to oral soft tissues were analyzed. METHODS: In the English language literature, 41 myofibroma and 12 myofibromatosis cases involving the oral soft tissues were found. From our files, three new myofibroma cases were added. RESULTS: Age at time of diagnosis of oral mucosa myofibroma ranged from birth to 70 years (mean 21.7 years), considerably higher than myofibroma in other parts of the body. Lesions occurred during the first decade (44%) and in the first year of life (17%). Male:female ratio was 1:1.6, contrary to the male predominance in other parts of the body. Common sites were the tongue (32%) and buccal mucosa (18%). Treatment was local excision, either complete (n = 13) or partial (n = 3), wide excision (n = 4), surgery, and chemotherapy (n = 1). Myofibromatosis involving oral soft tissues was diagnosed at birth in nine (75%) patients, within the first year in two, and as a young adult in one. Male:female ratio was 2:1. The tongue was the most common site (50%). Half the patients died of disseminated disease within a few days from birth, three were cured by partial or complete excision, and three experienced spontaneous regression. Histologically, oral mucosa myofibroma/myofibromatosis appearance agreed with findings in the literature. CONCLUSIONS: Myofibroma should be included in the clinical differential diagnosis of masses of the oral soft tissues, especially in the tongue and buccal mucosa of children and adolescents. Histological differential diagnosis includes benign and malignant spindle-shaped lesions. Treatment of choice is local excision.