Increased dopaminergic innervation in the brain of conditional mutant mice overexpressing Otx2: effects on locomotor behavior and seizure susceptibility.

The homeobox-containing transcription factor Otx2 controls the identity, fate and proliferation of mesencephalic dopaminergic (mesDA) neurons. Transgenic mice, in which Otx2 was conditionally overexpressed by a Cre recombinase expressed under the transcriptional control of the Engrailed1 gene (En1(Cre/+); tOtx2(ov/+)), show an increased number of mesDA neurons during development. In adult mice, Otx2 is expressed in a subset of neurons in the ventral tegmental area (VTA) and its overexpression renders mesDA more resistant to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-HCl (MPTP) neurotoxin. Here we further investigated the neurological consequences of the increased number of mesDA neurons in En1(Cre/+); tOtx2(ov/+) adult mice. Immunohistochemistry for the active, glycosylated form of the dopamine transporter (glyco-Dat) showed that En1(Cre/+); tOtx2(ov/+) adult mice display an increased density of mesocortical DAergic fibers, as compared to control animals. Increased glyco-Dat staining was accompanied by a marked hypolocomotion in En1(Cre/+); tOtx2(ov/+) mice, as detected in the open field test. Since conditional knockout mice lacking Otx2 in mesDA precursors (En1(Cre/+); Otx2(floxv/flox) mice) show a marked resistance to kainic acid (KA)-induced seizures, we investigated the behavioral response to KA in En1(Cre/+); tOtx2(ov/+) and control mice. No difference was observed between mutant and control mice, but En1(Cre/+); tOtx2(ov/+) mice showed a markedly different c-fos mRNA induction profile in the cerebral cortex and hippocampus after KA seizures, as compared to controls. Accordingly, an increased density of parvalbumin (PV)-positive inhibitory interneurons was detected in the deep layers of the frontal cortex of naïve En1(Cre/+); tOtx2(ov/+) mice, as compared to controls. These data indicate that Otx2 overexpression results in increased DAergic innervation and PV cell density in the fronto-parietal cortex, with important consequences on spontaneous locomotor activity and seizure-induced gene expression. Our results strengthen the notion that Otx2 mutant mouse models are a powerful genetic tool to unravel the molecular and behavioral consequences of altered development of the DAergic system.

[Primary malignant schwannoma of the uterine cervix: a malignant tumor with unusual behaviour. A case report]. / Schwannoma maligno primitivo della cervice uterina: un tumore maligno a comportamento inusuale. Caso clinico.

Malignant tumors of peripheral nerves (MPNST) represent approximately 5-10% of all soft tissue sarcomas and usually are in relationship with a major nerve. Primary cervical malignant Schwannomas are very rare neural sheat tumors that, grossly and clinically, are misdiagnosed for other more frequent lesions of the uterine cervix. We report a case of primary cervical malignant Schwannoma in a 27 years old female with atypical bleeding. The lesion is characterized by densely packed spindle cells with nuclear atypia and high mitotic rate. Immuno-histochemical stains are positive for vimentin and S-100 but negative for HMB-45, keratins, desmin and actin. After 34 months the patient is disease free. To our knowledge, this is the seventh case described.

[Retroperitoneal Pacinian neuroma: report of a rare lesion in an uncommon location]. / Neuroma paciniano retroperitoneale: una lesione rara a localizzazione inusuale.

Pacinian neuroma is an extremely rare benign tumor which has only occasionally been reported in the literature. To date, this lesion has usually been observed in the hand and foot; only one had intra-abdominal localization. Local trauma is reported in the most of these cases. We describe the first case of retroperitoneal pacinian neuroma. The lesion was observed as an incidental finding in a 75-year-old man who underwent laparotomy for aortic aneurysm. Here are discussed the differential diagnosis and a complete literature review on the topic.

Phospholipase C delta2 expression characterizes the neoplastic transformation of the human gastric mucosa.

The expression, cellular distribution, and activity of PIP(2)-specific phospholipase C (PLC) in healthy human gastric-mucosa cells have been recently studied in our laboratories and a direct evidence for an almost exclusive expression of PLC beta isoforms, with the exception of PLC beta4, has been provided. These results addressed our attention to possible modification of PLC expression and activity during neoplastic transformation of the human gastric mucosa. In the present article we present results indicating that PLC delta2 is markedly expressed in type II intestinal metaplasia and in the adenocarcinoma whereas traces of other PLC isoforms were sometime detected. Interestingly, we found that type I intestinal metaplasia was in the majority of the cases PLC delta2-negative, but when expressed, this type of metaplasia generally considered as benignant, always evolved toward neoplastic transformation. These results therefore readdress the question of surveillance of the patients with type I intestinal metaplasia and suggest that PLC delta2 expression might be a possible marker of gastric malignant transformation.