Blood immune cells as potential biomarkers predicting relapse-free survival of stage III/IV resected melanoma patients treated with peptide-based vaccination and interferon-alpha.

Introduction: Despite the recent approval of several therapies in the adjuvant setting of melanoma, tumor relapse still occurs in a significant number of completely resected stage III-IV patients. In this context, the use of cancer vaccines is still relevant and may increase the response to immune checkpoint inhibitors. We previously demonstrated safety, immunogenicity and preliminary evidence of clinical efficacy in stage III/IV resected melanoma patients subjected to a combination therapy based on peptide vaccination together with intermittent low-dose interferon-α2b, with or without dacarbazine preconditioning (https://www.

Exploiting natural antiviral immunity for the control of pandemics: Lessons from Covid-19.

The outbreak of coronavirus disease 2019 (COVID-19), triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the disruptive global consequences in terms of mortality and social and economic crises, have taught lessons that may help define strategies to better face future pandemics. Innate and intrinsic immunity form the front-line natural antiviral defense. They involve both tissue-resident and circulating cells, which can produce anti-viral molecules shortly after viral infection.

Antiviral and immunomodulatory interferon-beta in high-risk COVID-19 patients: a structured summary of a study protocol for a randomised controlled trial.

Objectives: The primary objective of the study is to demonstrate the efficacy of low-dose IFN-β in reducing the risk of SARS-CoV-2 recently infected elderly patients to progress towards severe COVID-19 versus control group within 28 days. Secondary objectives are: 1) To assess the reduction in Intensive Care Unit (ICU) admission in patients treated with IFN-β versus control group within 28 days of randomization 2) To assess the reduction in number of deaths in IFN- β compared to control group (day 28) 3) To evaluate the increase in proportion of participants returning to negative SARS-CoV-2 RT-PCR in IFN-β -treated versus control group at Day 14 and Day 28 4) To assess the increase in SARS-CoV-2-specific binding antibody titers in IFN-β compared to control group (day 28) 5) To assess the safety of IFN-β -treated patients versus control group TRIAL DESIGN: Randomized, Open-Label, Controlled, Superiority Phase II Study. Patients, who satisfy all inclusion criteria and no exclusion criteria, will be randomly assigned to one of the two treatment groups in a ratio 2:1 (IFN-treated versus control patients).

Expression of different forms of transglutaminases by immature cells of Helianthus tuberosus sprout apices.

Immature cells of etiolated apices of sprouts growing from Helianthus tuberosus (H. t.) tubers showed Ca(2+)-dependent transglutaminase (TG, EC 2.

Subclinical erectile dysfunction: proposal for a novel taxonomic category in sexual medicine.

The definition of erectile dysfunction currently used and accepted worldwide does not encompass all possible changes to male erection. Partial, temporary, or episodic absence of erection is not considered as true erectile dysfunction. This leads to a lack of diagnosis and therapy and perhaps even the risk of the subsequent development of overt impotence.

The effect of benzodiazepines and flumazenil on motor cortical excitability in the human brain.

In the present study, the effects of benzodiazepines (diazepam) were evaluated in terms of cortical excitability changes, as tested with transcranial magnetic simulation (TMS). In particular, analyzed were drug-induced changes regarding two selected parameters of TMS: (1) the cortical excitability threshold and (2) the silent period duration (SP). For this purpose, we evaluated the effects of long-term therapy with diazepam in the patients affected by anxiety disorders and the changes induced by single oral doses of diazepam in both healthy controls and patients.

Inhibition of melanoma pulmonary metastasis by methylxanthines due to decreased invasion and proliferation.

Theophylline- and caffeine-treated B16-F10 cells exhibited low adhesion to laminin/collagen type IV and reduced invasion through Matrigel in an in vitro assay. In contrast, theobromine appeared ineffective. When young adult C57BL/6 mice were injected intravenously with theophylline-treated B16-F10 cells, the number of surface lung tumours was markedly reduced.

Reduction of excitation by interleukin-1 beta in rat neocortical slices visualized using infrared-darkfield videomicroscopy.

The cytokine interleukin-1 beta (IL-1 beta) is thought to be critically involved in the neuroendocrine and behavioral changes which occur in response to systemic infection. In the present study, we have employed the novel technique of infrared-darkfield videomicroscopy to examine the effect of IL-1 beta on the intrinsic optical signal (IOS), an indicator of the spread of neuronal excitation and synaptic transmission in the mammalian central nervous system. Low doses of IL-1 beta delivered exogenously to rat neocortical slices produced a reduction of the area of the column-like IOS evoked by orthodromic stimulation.

Towards a neurophysiological marker of amyotrophic lateral sclerosis as revealed by changes in cortical excitability.

Motor evoked potentials (MEPs) to magnetic trans cranial stimulation (TCS) were recorded in 47 patients with amyotrophic lateral sclerosis (ALS) in order to evaluate both excitability and conductivity changes relating to central motor pathways. The results were compared with those obtained from a control population of 43 subjects, 34 patients with definite multiple sclerosis (MS) and 15 patients with a rigid early from of Parkinson's disease (PD). The excitability threshold to TCS was higher in ALS patients for both upper and lower limbs compared with both controls and PD patients, but lower than that of MS patients.

Identification of a substrate site for transglutaminases on the human protein synthesis initiation factor 5A.

Protein synthesis initiation factor 5A (eIF-5A) from human erythrocytes was found to be a substrate for both plasma transglutaminase (Factor XIIIa) and guinea pig liver transglutaminase (GPLTG). When purified eIF-5A was incubated with GPLTG or Factor XIIIa in the presence of succinylated beta-casein, a covalent complex was identified. By isolating and analysing the product of the transglutaminases (TGases) reaction, the site of modification on eIF-5A has been identified as the unique amino acid hypusine.

Myocardial release of malondialdehyde and purine compounds during coronary bypass surgery.

Background: Free radicals and lipid peroxidation have been suggested to play an important role in the pathophysiology of myocardial reperfusion injury. The purpose of the present study was to monitor myocardial malondialdehyde (MDA) production as an index of lipid peroxidation during ischemia-reperfusion sequences in patients undergoing elective coronary bypass grafting. There has been a lot of debate on the role of xanthine oxidase as a potential superoxide anion generator and thus lipid peroxidation in human myocardium.

Optimization of pre-, intra- and postoperative hyperthermic treatment in inoperable lower bowel and liver tumors.

Traditional therapies in malignant tumors are often inadequate, either because the tumors aren not responsive or because the tolerance dosage has little effect. With this in mind, our study examined advanced tumors of the lower bowel and liver. We evaluated the results of 10 cases of anorectal epidermoid cancer.

Phospholipase A2 affects the activity of fusicoccin receptors.

Biochemical properties of fusicoccin receptors are strongly influenced by the phospholipid environment. In this report we have studied the effect of different exogenous phospholipases on fusicoccin binding ability of both plasma membrane and solubilised receptors. Among the phospholipases tested only phospholipase A2 showed an inhibitory effect on fusicoccin binding.

Corneal topographic analysis of photorefractive keratectomy in 175 myopic eyes.

Videokeratography is a useful method for postoperative evaluation of photorefractive keratectomy (PRK). The aim of this study was to evaluate the percentage of decentration, the relationship between decentration relative to the corneal apex, postoperative astigmatism, and the relationship between decentration and best corrected Snellen visual acuity. Using the TMS-1 videokeratoscope we analyzed the corneal topography of 175 myopic eyes treated with PRKs ranging between -1.

Simultaneous occurrence of monoclonal gammopathy and acute secondary leukemia with overexpression of P-glycoprotein.

A 52-year-old woman, previously treated with chemo- and radiotherapy for Hodgkin's disease, developed an acute non-lymphoid leukemia and, contemporarily, an IgG-kappa paraproteinemia. Cytogenetic analysis showed a major clone, representing 90% of observed metaphases, with monosomy of chromosomes 5 and 14. In addition, leukemic cells exhibited a high expression of the P-glycoprotein, a transmembrane glycoprotein involved in the multidrug-resistance mechanism.

Age-related changes of motor evoked potentials in healthy humans: non-invasive evaluation of central and peripheral motor tracts excitability and conductivity.

A comparative analysis of the corticospinal tract nervous propagation and excitability threshold was carried out in young (25 subjects, age range 16-35 years) and in elderly (40 subjects, 51-86 years) populations of healthy volunteers. Motor evoked potentials (MEPs) were recorded from the hand and foot muscles following transcranial magnetic stimulation (TCS) during complete relaxation and active contraction of the target muscles. Threshold intensities corresponded to the stimulator's output eliciting liminal MEPs in about 50% of stimuli during relaxation.

Functionally active complement is present in human ovarian follicular fluid and can be activated by seminal plasma.

Human ovarian preovulatory follicular fluids (FF) from 10 women were analysed for their complement contents. Functionally active complement was detected in all the fluids studied in amounts similar to those present in normal human serum. Pooled FF was challenged by seminal plasma in order to determine whether seminal plasma could activate FF complement, the pattern of such an activation and the possible consequences on the reproductive function.

Selective inhibition of HIV replication by adriamycin in macrophages but not in lymphocytes.

Adriamycin (ADR) is an anticancer drug commonly used in the treatment of HIV-related cancers. Due to its effect on DNA metabolism, ADR might be able to modulate HIV replication in monocyte-macrophages (M/M), resting cells potentially less sensitive to the toxic effect of this drug. Thus, we assessed the efficacy of ADR against HIV replication in both lymphocytes and M/M.

Modulation of insulin secretion by diazepam binding inhibitor and its processing products.

The effect of purified rat brain diazepam binding inhibitor (DBI) and that of synthetic DBI fragments DBI33-50 [octadecaneuropeptide (ODN)], DBI17-50 [triakontatetraneuropeptide (TTN)], DBI42-50 and DBI53-62 were studied on glucose-induced secretion of insulin from isolated rat pancreatic islets in both static incubation and perifusion experiments. DBI and ODN did not affect the secretion of insulin in the presence of 2.8 mM glucose (basal condition) but reduced the release of insulin induced by 16.

Control of ColE1 plasmid replication by antisense RNA.

One of the two major classes of regulatory strategies that control plasmid copy number involves recognition via base pairing between two plasmid-encoded complementary RNAs. The detailed analysis of this control circuitry has revealed some features of regulatory mechanisms based on RNA-RNA interaction that distinguish them from those based on protein-nucleic acid interaction. These features provide a framework with which to understand other regulatory mechanisms based on RNA-RNA interaction, and will aid in the design of efficient artificial antisense RNA systems.

High amounts of beta-endorphin in peripheral blood mononuclear cells from HANE patients.

We measured peripheral blood mononuclear cells (PBMC) beta-endorphin (BE) in patients suffering from hereditary angioneurotic edema (HANE), a disease attributed to C1-esterase inhibitor (C1INH) deficiency inherited as an autosomal dominant trait. Two orders of considerations prompted us to undertake the study reported herein: the presence of elevated plasma BE concentrations in HANE and the demonstration of BE-immunoreactivity in human unstimulated peripheral blood leukocytes obtained from healthy volunteers. Our results show that patients suffering from HANE have a very high BE presence in uncultured, unstimulated PBMC and in unstimulated PBMC cultured for 48 h.

Structural chromosomal rearrangements in HpaII-treated human lymphocytes.

Restriction endonucleases have been shown to induce chromosome damage in a variety of cultured cells. We recently reported the coincidence between MspI-induced breakage and the location of common fragile sites. We have extended our study to HpaII, which induced a 4.

Expression of the mRNA for the ligand of c-kit in mouse Sertoli cells.

The expression of the mRNA for SLF (the c-kit ligand), a product of the "steel" locus, has been investigated in postnatal mouse testis and homogeneous populations of testicular cells. The message was found expressed in postnatal mouse testis but not in germ cells. Studies on primary mouse Sertoli cell cultures from 18 day old mice show that Sertoli cells are the site of SLF mRNA expression in the seminiferous tubules.

HTLV-I and HIV-1 infection in patients with lymphadenopathy syndrome detected during routine breast screening at a tumor prevention center.

Lymphadenopathy with no apparent cause had been reported in a group of women participating in a mammary tumor prevention program. A screening for retrovirus infection was organized to detect the virus as possible etiological agents. Data show a high percentage of positivity for HIV-1 among these lymphadenopathy patients, and surprisingly for HTLV-I, while no such positivity for either virus was found in matched controls or in patients where a different causal agent for lymphadenopathy was found.