Identification of a novel gp100/pMel17 peptide presented by HLA-A*6801 and recognized on human melanoma by cytolytic T cell clones

Melanoma-associated peptides recognized by cytolytic T lymphocytes (CTL) in the context of several histocompatibility leukocyte antigens (HLA) are required for the development of specific immunotherapies. Using a transient transfection assay into COS-7 cells, we identified the gp100/pMel17 melanosomal protein as the shared antigen recognized by three independent CD8+ CTL clones in HLA-A*6801-restricted fashion. This finding was confirmed by the correlation between lack of gp100/pMel17 protein in a number of HLA-A*6801-positive melanomas and their resistance to lysis/cytokine production by the specific effectors. The gp100/pMel17 antigenic epitope was identified based on recognition of subfragments and on a computer-based prediction algorithm. Among a panel of gp100/pMel17-derived synthetic peptides only the 10-mer HTMEVTVYHR (gp100/pMel17182-191) induced tumor necrosis factor (TNF) release by CTL clones when pulsed on suitable target cells whereas both the 10-mer and the shorter 9-mer gp100/pMel17183-191 sensitized the same antigen-pulsed cells to lysis. In conclusion, the identification of the HTMEVTVYHR peptide will extend to HLA-A*6801 melanoma patients the possibility to exploit gp100/pMel17 melanosomal protein for experimental and clinical studies.     

A cell surface monoclonal antibody (H366) helps to discriminate human cytotoxic from suppressor T cells.

A study has been undertaken to differentiate T cytotoxic (Tc) and T suppressor (Ts) cell subsets using a monoclonal antibody termed H366 (mouse IgG2b) previously reported to phenotype natural killer and killer (NK/K) cells. Mononuclear cell suspensions from 14 normal subjects were depleted of H366+ cells by means of complement dependent cytotoxicity and the remaining cells were phenotyped with CD8 and CD4 monoclonal antibodies. The effects of depletion with H366 plus complement (C1) on the induction and activity of suppressor and cytotoxic T cells was also examined. The results indicate that H366 antibody recognizes in addition to NK/K cells, a population of Tc but not Ts or helper cells. Therefore, H366 antibody can be useful for obtaining Ts enriched lymphocyte subpopulations and this property may also be used for the enumeration of suppressor cells in the peripheral blood in disease states.     

Soluble CD30 serum antigen in Kawasaki disease

⁴Very high levels of sCD30, a glycoprotein surface antigen expressed by T lymphocytes and other mononuclear cells of the immune system, were found in serum samples from 10 children with typical Kawasaki disease (KD), but not in blood specimens from a vast cohort of paediatric control subjects. These data strongly support an involvement of CD30+T cells in the immune processes which take place at the level of lymphoid organs during the acute phase of KD.     

Nutritional Status after Roux-En-Y (Rygb) and One Anastomosis Gastric Bypass (Oagb) at 6-Month Follow-Up: A Comparative Study

Introduction: Roux-en-Y gastric bypass (RYGB) and one anastomosis gastric bypass (OAGB) are two effective bariatric surgical procedures with positive outcomes in terms of weight loss, comorbidities remission, and adverse events profiles. OAGB seems to carry a higher risk of malnutrition, but existing data are controversial. The aim of this study is to objectively evaluate and compare malnutrition in patients undergoing RYGB and OAGB. Methods: Retrospective monocentric study of obese patients undergoing RYGB or OAGB between the 15 September 2020 and the 31 May 2021. Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score and compared between groups. The primary outcome was the mean CONUT score at 6 months. The secondary outcomes included the incidence of malnutrition, comorbidities, including hypertension, insulin resistance and type II diabetes mellitus, and weight loss. Results: 78 patients were included: 30 underwent RYGB and 48 underwent OAGB. At 6-Month Follow-Up there was no difference between groups in the mean CONUT score nor in incidence of malnutrition. In both groups, the nutritional status significantly worsened 6 months after surgery (preoperative and postoperative score of 0.48 ± 0.9 and 1.38 ± 1.5; p = 0.0066 for RYGB and of 0.86 ± 1.5 and 1.45 ± 1.3; p = 0.0422 for OAGB). Type II Diabetes mellitus (DMII) and hypertension remission were significant in the OAGB group with a 100% relative remission in the DMII-OAGB group (p = 0.0265), and a 67% relative remission in the hypertension-OAGB group (p = 0.0031). Conclusions: No difference in nutritional status has been detected between patients undergoing RYGB or OAGB at the 6-Month Follow-Up. Both procedures may have significant mal-absorptive effects leading to decline in nutritional status. OAGB may be more efficacious in inducing DMII and hypertension remission. Larger prospective studies dedicated specifically to nutritional status after gastric bypass are needed to confirm the impact of different bypass procedures on nutritional status.     

Chronic rejection after liver transplantation: Opening the Pandora’s box

Chronic rejection (CR) of liver allografts causes damage to intrahepatic vessels and bile ducts and may lead to graft failure after liver transplantation. Although its prevalence has declined steadily with the introduction of potent immunosuppressive therapy, CR still represents an important cause of graft injury, which might be irreversible, leading to graft loss requiring re-transplantation. To date, we still do not fully appreciate the mechanisms underlying this process. In addition to T cell-mediated CR, which was initially the only recognized type of CR, recently a new form of liver allograft CR, antibody-mediated CR, has been identified. This has indeed opened an era of thriving research and renewed interest in the field. Liver biopsy is needed for a definitive diagnosis of CR, but current research is aiming to identify new non-invasive tools for predicting patients at risk for CR after liver transplantation. Moreover, the minimization or withdrawal of immunosuppressive therapy might influence the establishment of subclinical CR-related injury, which should not be disregarded. Therapies for CR may only be effective in the “early” phases, and a tailored management of the immunosuppression regimen is essential for preventing irreversible liver damage. Herein, we provide an overview of the current knowledge and research on CR, focusing on early detection, identification of non-invasive biomarkers, immunosuppressive management, re-transplantation and future perspectives of CR.     

Delirium in COVID-19 patients: a multicentric observational study in Italy

Neurological Sciences - Although recent data show that SARS-CoV-2 infection seems to affect the central nervous system (CNS), little is known about the neuropsychiatric effects resulting from this...     

Cerebral venous thrombosis without thrombocytopenia after a single dose of COVID-19 (Ad26.COV2.S) vaccine injection: a case report

Neurological Sciences - The coronavirus pandemic became the hard challenge for the modern global health system. To date, vaccination is the best strategy against Sars-Cov-2-related illness. About 3...     

Silicone index: an alternative approach for tooth fragment reattachment

Tooth fragment reattachment is a simple, conservative, fast, and affordable treatment option for fractured teeth when the fragment is available. However, this technique can present some difficulties, among which is the possibility of the fragment being positioned and bonded inadequately. To avoid this situation, it is necessary to establish a reference for the adequate positioning of the fragment using a silicone index. CLINICAL SIGNIFICANCE: This article presents an alternative approach for better handling of tooth fragments resulting from trauma by using a silicone index as a guide to proper positioning and bonding.     

A simplified approach for layering composite resin restorations

Although composite restorations can provide excellent results, it is possible that general dentists might find some of the currently proposed techniques to be complicated and demanding. This article reviews some of these concepts and presents a protocol that makes highly esthetic restorations simple yet predictable.