Hyperinsulinism of infancy associated with a novel splice site mutation in the SCHAD gene

Fatty acids play an important role in regulating insulin secretion, but the mechanisms are unclear. We report a case of a novel splice site mutation in the short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) gene associated with hyperinsulinism. This mutation resulted in a nearly complete absence of immunoreactive protein and a decrease in fibroblast SCHAD activity.     

Chemokine receptor expression in EBV-associated lymphoproliferation in hu/SCID mice: implications for CXCL12/CXCR4 axis in lymphoma generation

The mechanisms by which intraperitoneal injection of peripheral blood mono-nuclear cells (PBMCs) from Epstein-Barr virus (EBV)-seropositive donors into severe combined immunodeficient (SCID) mice gives rise to lymphomas (hu/SCID tumors) are far from clear. This study addressed whether chemokine receptors and their ligands could be implicated in this experimental model. CXCR4 was found to be highly expressed in hu/SCID tumors; surface expression of CXCR4 was prevalently limited to a tumor cell subset poorly expressing CD23, whereas the CXCR4 ligand, CXCL12, was predominantly expressed by the tumor subpopulation expressing CD23. In vitro inhibition of this autocrine/paracrine CXCL12/CXCR4 axis significantly inhibited lymphoma proliferation and survival. Furthermore, CXCL12 was expressed in cells recovered from the mouse peritoneal cavity early after PBMC transfer as well as by EBV-transformed B cells but not by resting or activated B lymphocytes; also, lymphoma development was associated with a dramatic increase in the levels of murine CXCL12 present in the peritoneal cavity. Finally, antagonizing the CXCL12/CXCR4 axis in vivo strongly counteracted lymphoma development. These studies demonstrate that CXCL12 expression may be associated with EBV infection and suggest that the CXCR4/CXCL12 axis may participate in the EBV-associated lymphomagenesis process in immunodeficient hosts.     

Phenotypic and functional analyses of dendritic cells in patients with lymphoproliferative disease of granular lymphocytes (LDGL)

We investigated whether dendritic cells (DCs) play a role in favoring granular lymphocyte (GL) proliferation in patients with lymphoproliferative disease of granular lymphocytes (LDGL). The presence of in vivo circulating DCs was studied in 11 patients (5 CD3+ and 6 CD3- LDGL). Autologous immature (iDCs) and mature (mDCs) DCs generated in vitro were studied for stimulatory activity on cell proliferation of CD3+ and CD3- GLs. The topographic organization of GLs and DCs was also studied in bone marrow (BM) biopsies. Peripheral blood (PB) CD3- GLs from patients showed significant proliferative activity in the presence of iDCs and mDCs. Conversely, monoclonal CD3+ GLs were unresponsive to autologous and allogeneic PB DCs. Analysis of BM biopsies demonstrated a topographic distribution of DCs and GLs that indicates contact between the 2 cell types. On functional assays, DCs obtained from BM were more efficient than PB DCs in stimulating CD3- GLs, and surprisingly, a low but definite stimulatory effect was demonstrated also on CD3+ GLs. The putative contact between DCs and GLs in the BM and, more crucial, the proliferative response of discrete GL populations to DC stimulation suggest the presence of a specific antigen within BM DCs, providing evidence for a role of DCs in the pathogenesis of LDGL.     

Role of gut microbiota-immunity axis in patients undergoing surgery for colorectal cancer: Focus on short and long-term outcomes

Human body is colonized by a huge amount of microorganisms mostly located in the gastrointestinal tract. These dynamic communities, the environment and their metabolites constitute the microbiota. Growing data suggests a causal role of a dysbiotic microbiota in several pathologies, such as metabolic and neurological disorders, immunity dysregulations and cancer, especially the well-studied colorectal cancer development. However, many were preclinical studies and a complete knowledge of the pathogenetic mechanisms in humans is still absent.The gut microbiota can exert direct or indirect effects in different phases of colorectal cancer genesis. For example, Fusobacterium nucleatum promotes cancer through cellular proliferation and some strains of Escherichia coli and Bacteroides fragilis produce genotoxins. However, dysbiosis may also cause a proinflammatory state and the stimulation of a Th17 response with IL-17 and IL-22 secretion that have a pro-oncogenic activity, as demonstrated for Fusobacterium nucleatum. Microbiota has a crucial role in several stages of postoperative course;dysbiosis in fact seems related with surgical site infections and Enterococcus faecalis(and other collagenase-producers microbes) are suggested as a cause of anastomotic leak. Consequently, unbalanced presence of some species, together with altered immune response may also have a prognostic role. Microbiota has also a substantial role in effectiveness of chemotherapy, chemoresistance and in the related side effects. In other words, a complete knowledge of the fine pathological mechanisms of gut microbiota may provide a wide range of new diagnostic tools other than therapeutic targets in the light of tailored medicine.     

Menstrual migraine: what it is and does it matter?

Journal of Neurology - The diagnostic criteria of menstrual migraine (MM), migraine related to menstruation and pure menstrual migraine, are placed in the appendix of the International...     

Evidence for interhemispheric imbalance in stroke patients as revealed by combining transcranial magnetic stimulation and electroencephalography

Interhemispheric interactions in stroke patients are frequently characterized by abnormalities, in terms of balance and inhibition. Previous results showed an impressive variability, mostly given to the instability of motor‐evoked potentials when evoked from the affected hemisphere. We aim to find reliable interhemispheric measures in stroke patients with a not‐evocable motor‐evoked potential from the affected hemisphere, by combining transcranial magnetic stimulation (TMS) and electroencephalography. Ninteen stroke patients (seven females; 61.26 ± 9.8 years) were studied for 6 months after a first‐ever stroke in the middle cerebral artery territory. Patients underwent four evaluations: clinical, cortical, corticospinal, and structural. To test the reliability of our measures, the evaluations were repeated after 3 weeks. To test the sensitivity, 14 age‐matched healthy controls were compared to stroke patients. In stroke patients, stimulation of the affected hemisphere did not result in any inhibition onto the unaffected. The stimulation of the unaffected hemisphere revealed a preservation of the inhibition mechanism onto the affected. This resulted in a remarkable interhemispheric imbalance, whereas this mechanism was steadily symmetric in healthy controls. This result was stable when cortical evaluation was repeated after 3 weeks. Importantly, patients with a better recovery of the affected hand strength were the ones with a more stable interhemispheric balance. Finally, we found an association between microstructural integrity of callosal fibers, suppression of interhemispheric TMS‐evoked activity and interhemispheric connectivity. We provide direct and sensitive cortical measures of interhemispheric imbalance in stroke patients. These measures offer a reliable means of distinguishing healthy and pathological interhemispheric dynamics.