Pharmacological characterization of BDNF promoters I, II and IV reveals that serotonin and norepinephrine input is sufficient for transcription activation.

Compelling evidence has shown that the effects of antidepressants, increasing extracellular serotonin and noradrenaline as a primary mechanism of action, involve neuroplastic and neurotrophic mechanisms. Brain-derived neurotrophic factor (BDNF) has been shown to play a key role in neuroplasticity and synaptic function, as well as in the pathophysiology of neuropsychiatric disorders and the mechanism of action of antidepressants. The expression of BDNF is mediated by the transcription of different mRNAs derived by the splicing of one of the eight 5' non-coding exons with the 3' coding exon (in rats). The transcription of each non-coding exon is driven by unique and different promoters. We generated a gene reporter system based on hippocampal and cortical neuronal cultures, in which the transcription of luciferase is regulated by BDNF promoters I, II, IV or by cAMP response element (CRE), to investigate the activation of selected promoters induced by monoaminergic antidepressants and by serotonin or noradrenaline agonists. We found that incubation with fluoxetine or reboxetine failed to induce any activation of BDNF promoters or CRE. On the other hand, the incubation of cultures with selective agonists of serotonin or noradrenaline receptors induced a specific and distinct profile of activation of BDNF promoters I, II, IV and CRE, suggesting that the monoaminergic input, absent in dissociated cultures, is essential for the modulation of BDNF expression. In summary, we applied a rapidly detectable and highly sensitive reporter gene assay to characterize the selective activation profile of BDNF and CRE promoters, through specific and different pharmacological stimuli.

Met signaling mutants as tools for developmental studies.

The Met receptor is widely expressed in embryonic and adult epithelial tissues; its ligand (hepatocyte growth factor/scatter factor, HGF/SF) is expressed in the mesenchymal component of various organs. The generation of hgf and met null mice has revealed an essential role for this ligand-receptor pair in the development of the placenta, liver, and limb muscles. However the early lethality of the null mutants has precluded analysis of Met function in late development. To extend the possible observation period, we generated mutant metalleles of different severity. This was done by impairing the ability of the receptor to transduce the HGF/SF signal, via mutation of consensus sequences in the multifunctional docking site present in the C-terminal tail of the receptor. Mice expressing a Met mutant still active as a kinase, but unable to recruit its effectors, died in mid-gestation with the same phenotype as the metknockout, proving the importance of phosphotyrosine-SH2 interactions in vivo. Mice expressing a Met receptor with partial loss of signaling function survived until birth and revealed novel aspects of HGF/SF-Met function during muscle development.

ErbB-3 and ErbB-4 expression in the mouse olfactory system.

The interplay between neuregulins and the ErbB receptor family has a pivotal role in the development of several tissues, including the nervous system, and is maintained in the adult olfactory system where extensive plasticity and neurogenesis are retained. In the present work we show the immunohistochemical localization of ErbB-3 and ErbB-4 in the olfactory system of adult normal and lesioned mice. The expression of ErbB-3 is demonstrated to be restricted to the ensheathing cells of the olfactory nerve and to a few substentacular cells of the olfactory epithelium (OE). ErbB-3 staining circumvents the glomeruli but is never observed inside them or elsewhere in the adult olfactory bulb. Conversely, ErbB-4 immunoreactivity is found in all the periglomerular and mitral/tufted cells of the olfactory bulb (OB) and to a minor extent in the olfactory neurons and basal cells of the OE. Interestingly enough, cells coming out from the rostral migratory stream of the subependymal layer (SEL), as well as isolated cells in the granule cell layer, possibly migrating cells, strongly stained for ErbB-4 expression. Lesions of the olfactory epithelium have been performed by unilateral intranasal irrigation with ZnSO4 and 3 weeks after the irrigation, the olfactory bulbs were analyzed for olfactory marker protein (OMP), tyrosine hydroxylase (TH), ErbB-3 and ErbB-4 expression. In the deafferented OB, the drastic loss of immunoreactivity for OMP was accompanied by a strong reduction of ErbB-3 expression. Most of the deafferented dopaminergic interneurons switched off TH expression. In the deafferented periglomerular and mitral/tufted cells ErbB-4 expression was turned off and down, respectively. No differences were noted at the granular cell layer level in the deafferented OB with respect to control. Taken together our results suggest that, in normal conditions, neuregulins are involved in the survival of the ensheathing cells of the olfactory nerve through ErbB-3 activation and in the functional activity of postsynaptic neurons through ErbB-4 activation.

Plexiform neurofibroma of the cervical portion of the vagus nerve.

The authors describe a rare case of plexiform neurofibroma of the cervical portion of the vagus nerve, and discuss its aetiopathogenesis, clinical, histological and therapeutic features, emphasizing the difference from other benign tumours of the vagus nerve. The clinical characteristics of the mass, ultrasound tomography, CT scanning and digital subtraction angiography were useful in defining its extension and relationships with the surrounding structures. Surgery is the treatment of choice. After mentioning the most commonly employed surgical approaches, they emphasize the advantages of the lateral-cervical approach which allows a wide exposure of the possible sites of origin of the tumour and its complete removal. Finally they stress the need of an accurate histological and immunohistochemical examination in order to differentiate neurofibromas from neurilemmomas.

[Transformation of Waldenström disease into chronic myeloid leukemia]. / Trasformazione di malattia di Waldenström in leucemia mieloide cronica.

The authors describe a case of a 83 years old patient affected with Waldenström disease whose shift in chronic myelogenous leukaemia is surprising because the quickness of the fact and, even more, because the following very fast appearance of quickly fatal paravertebral granulocytic sarcoma, as extramedullary blast crisis expression. This feature appears unusual in old subject.

[Endometriosis of the abdominal wall. A report of a case secondary to cesarean section]. / Endometriosi della parete addominale. Descrizione di un caso secondario a parto cesareo.

The Authors report a case of endometriosis of the surgical scar following caesarean section. The patient, arrived at surgical observation for a doubtful foreign body granuloma, underwent a diagnostic biopsy of the lesion. Histological examination confirmed the endometriosis nature of the lesion. Before surgical removal, adjuvant therapy based on GnRH analog was performed with the aim to reduce the volume of the lesion. After removal a cycle of therapy with GnRH analog was performed in oder to exclude possible residual pathologic microscopic lesions.

[Immunohistochemistry in cytologic diagnosis using fine needle aspiration]. / L'immunoistochimica nella diagnostica citologica per aspirazione con ago sottile.

The role of immunocytochemistry in fine-needle aspiration cytology. The Authors review the literature about fine-needle aspiration biopsy cytology in different organs and show the feasibility of the application to cytological specimen of immunocytochemical methods. Thus, they analyze 15 cases of tumors of various localization diagnosed by F.N.A.C. where immunocytochemistry succeeded in their correct typization. They also show the encouraging results of the immunocytochemical search of specific hormones in pituitary adenomas. Therefore the Authors emphasize the great usefulness of immunocytochemical techniques for the improvement of the diagnostic possibilities in the fine-needle aspiration cytology.

Cervical cord compression due to atypical primary neuroectodermal tumor (PNET): one-stage removal and combined cervical spine stabilization. Case report.

INTRODUCTION: The neuroectodermal tumor of bone constitutes a recently isolated neoplasm, which morphologically resembles the peripheral neuroepithelioma of soft tissue. The diagnosis is made by excluding readily classified small round cell neoplasms and then demonstrating the neural origin of the tumor by means of ultrastructural or immunocytochemical studies. CLINICAL CASE: We report a case of a primary neuroectodermal tumor (PNET) with atypical findings (primary cervical location, massive vertebral body infiltration and isolated neurological symptomatology). Total tumor removal was achieved by means of a one-stage three-level laminectomy (partial C5, total C6-C7), C6 somatectomy, and combined anterior and posterior cervical spinal instrumentation and fusion. CONCLUSIONS: Our case presents three peculiar features: 1) isolated myelopathic symptomatology (first case described); 2) primary isolated massive vertebral cervical involvement with intraspinal epidural extension (first case described); 3) one-stage tumor resection, fusion and instrumentation. Since radiation therapy causes tumor shrinkage but is not curative, radical removal is mandatory even with complex instrumentation procedures.

Morphologic and planimetric diagnosis of follicular thyroid lesions on fine needle aspiration cytology.

During 1989-1992, 2,729 fine needle aspiration biopsies were performed; 585 with histologic controls were reviewed. The aim of the study was to demonstrate the incidence of carcinoma in follicular-structured smears without nuclear enlargement, evaluated with planimetric techniques, and to suggest a new cytodiagnostic classification. Of 398 follicular-structured smears, 188 were colloid nodules, 38 were thyreocytic hyperplasias without nuclear atypia, 146 were predominantly follicular lesions (PFL) and 26 were follicular lesions with nuclear pleomorphism. The last showed a high incidence of neoplasia (69.2%) and carcinoma (46.1%) and the largest planimetric values for nuclear area, perimeter and maximum diameter. The second and third categories showed only a difference in the incidence of benign neoplasms (32.9 vs. 15.8%). These results suggest that six months of expectant management might be useful in simple follicular lesions, whereas a follicular pattern with nuclear enlargement requires surgical treatment for the strong possibility of carcinoma.