A Potential Role for Shed Soluble Major Histocompatibility Class I Molecules as Modulators of Neurite Outgrowth

The neurobiological activities of classical major histocompatibility class I (MHCI) molecules are just beginning to be explored. To further examine MHCI's actions during the formation of neuronal connections, we cultured embryonic mouse retina explants a short distance from wildtype thalamic explants, or thalami from transgenic mice (termed “NSE-Db”) whose neurons express higher levels of MHCI. While retina neurites extended to form connections with wildtype thalami, we were surprised to find that retina neurite outgrowth was very stunted in regions proximal to NSE-Db thalamic explants, suggesting that a diffusible factor from these thalami inhibited retina neurite outgrowth. It has been long known that MHCI-expressing cells release soluble forms of MHCI (sMHCI) due to the shedding of intact MHCI molecules, as well as the alternative exon splicing of its heavy chain or the action proteases which cleave off it's transmembrane anchor. We show that the diffusible inhibitory factor from the NSE-Db thalami is sMHCI. We also show that COS cells programmed to express murine MHCI release sMHCI that inhibits neurite outgrowth from nearby neurons in vitro. The neuroinhibitory effect of sMHCI could be blocked by lowering cAMP levels, suggesting that the neuronal MHCI receptor's signaling mechanism involves a cyclic nucleotide-dependent pathway. Our results suggest that MHCI may not only have neurobiological activity in its membrane-bound form, it may also influence local neurons as a soluble molecule. We discuss the involvement of complement proteins in generating sMHCI and new theoretical models of MHCI's biological activities in the nervous system

Acute splenic torsion in children: which is the best treatment? A case report

Wandering spleen is a clinical entity which rarely affects children and adolescents. This condition can be asymptomatic or responsible of chronic pain, but it appears as a surgical emergency when an acute twisting occurs. The risk of post-splenectomy sepsis in the pediatric population suggests a conservative approach whenever possible, and also in case of acute torsion, most authors prefer to preserve the spleen and perform a splenopexy. The Authors describe a case of a child with acute splenic torsion, in whom a conservative surgical approach was initially adopted. The conservative option has to be balanced with the risk of prolonged thrombocytopenia, multiple transfusions and a possible second procedure to remove the spleen

HEMATOMETRA IN UTERUS DIDELPHIS: A PITFALL IN TEENAGERS WITH LOWER ABDOMINAL MASS. REPORT OF TWO CASES

M\ufcllerian malformations represent a wide spectrum of anomaly of the female reproductive tract, usually detected at birth or at puberty. The presence of uterus didelphys and obstructed hemivagina, associated with ipsilateral renal agenesis, is known as Herlyn-Werner-Wunderlich syndrome, a rare congenital anomaly. Two cases of uterus didelphic and hematometra caused by vaginal septum are reported; the girls had a delayed diagnosis due to absence of a specific clinical feature. Clinicians must be aware of the existence of these malformations. An adequate radiological study is mandatory to assess the anatomic conformation, and to optimize the therapeutic procedure

Concurrent fibroadenoma and intraductal papilloma - A recurring complex lesion in a premenarcheal girl

Breast diseases are rare in childhood and adolescence, most lesions being fibroadenomas and papillomas. We report the case of an 11-year old girl with a complex breast lesion with hybrid features of fibroadenoma and intraductal papilloma with an early recurrence. Microscopically, the lesion was composed of dilated ducts showing intraluminal papillary projections with small to broad fibrovascular stalks. The typical leaf-like appearance of fibroadenoma was determined by the presence at the periphery of ducts compressed and distorted by the prominent stromal component. Despite its florid epithelial hyperplasia and mild cytological atypia (more evident in the relapse), immunohistochemical staining for p63 and smooth muscle actin highlighted a continuum outer myoepithelial layer, confirming the non-invasive appearance of the lesion. Two pathogenetic links have been hypothesized: one is based on the morphological continuum between these two entities, which may represent different evolutive stages in the same lesion; the other is based on epithelial/mesenchymal interactions. The possible malignant transformation of such complex lesion is also discussed, along with its differential diagnoses. The relevance of this case lies in its rarity, as well as in the therapeutic strategies related to its biological potential and to the necessity of a conservative treatment, due to the young age of the patient