Pulmonary Kaposi's sarcoma after heart transplantation: a case report

ABSTRACT: INTRODUCTION: Kaposi's sarcomas have been associated with different conditions of immunosuppression and are also known to be a typical complication of solid organ transplantations. CASE PRESENTATION: We report of a 65 year old man of Turkish origin with a history of heart transplantation 10 months ago who presented for clarification of his dyspnoea. The patient had a known history of chronic obstructive pulmonary disease and a smoking history of 40 pack years. Radiologically, three progressively growing intrapulmonary nodules were detected. The histology was diagnostic for a Kaposi's sarcoma. Visceral and especially primary intrapulmonary Kaposi's sarcomas are very rare and have been described to have a rather unfavourable prognosis. CONCLUSION: Even with a history suggestive for conventional lung cancer, Kaposi's sarcomas should be considered in patients after transplantation of solid organs. It should be noticed that in a minority of cases this tumour exists in the absence of the typical cutaneous lesions

Molecular Mimicry of Human Cytochrome P450 by Hepatitis C Virus at the Level of Cytotoxic T Cell Recognition

Hepatitis C virus (HCV) is thought to be involved in the pathogenesis of autoimmune hepatitis (AIH) type 2, which is defined by the presence of type I antiliver kidney microsome autoantibodies directed mainly against cytochrome P450 (CYP)2D6 and by autoreactive liver infiltrating T cells. Virus-specific CD8+ cytotoxic T lymphocytes (CTLs) that recognize infected cells and contribute to viral clearance and tissue injury during HCV infection could be involved in the induction of AIH. To explore whether the antiviral cellular immunity may turn against self-antigens, we characterized the primary CTL response against an HLA-A*0201–restricted HCV-derived epitope, i.e., HCV core 178–187, which shows sequence homology with human CYP2A6 and CYP2A7 8–17. To determine the relevance of these homologies for the pathogenesis of HCV-associated AIH, we used synthetic peptides to induce primary CTL responses in peripheral blood mononuclear cells of healthy blood donors and patients with chronic HCV infection. We found that the naive CTL repertoire of both groups contains cross-reactive CTLs inducible by the HCV peptide recognizing both CYP2A6 and CYP2A7 peptides as well as endogenously processed CYP2A6 protein. Importantly, we failed to induce CTLs with the CYP-derived peptides that showed a lower capacity to form stable complexes with the HLA-A2 molecule. These findings demonstrate the potential of HCV to induce autoreactive CD8+ CTLs by molecular mimicry, possibly contributing to virus-associated autoimmunity

Deletions within the 5′UTR of coxsackievirus B3: Consequences for virus translation and replication

AbstractKey features of an ideal RNA-based vaccine against coxsackievirus B3 (CVB3) are (i) limited genome replication/virus production (to minimize vaccine-related pathology) and (ii) abundant virus protein synthesis (to maximize immunogenicity). These attributes may apply to CVB3 RNAs lacking up to 250 nucleotides (nt) from their 5′ terminus; these RNAs do not give rise to infectious progeny, but they have been reported to retain the entire CVB3 IRES (mapped to nt ∼432–639) and to produce large quantities of viral protein in transfected cells. Here, we constructed five 5′ RNA deletion variants that, to our surprise, failed to protect against CVB3 challenge. We investigated the reasons for this failure and conclude that (i) a 5′ terminal deletion as short as 32 nt abolishes CVB3 RNA replication in transfected cells; (ii) this deleted RNA, and others with longer deletions, do not direct abundant protein synthesis in transfected cells, probably as a consequence of their replicative incapacity; and (iii) the CVB3 IRES is substantially larger than previously thought, and its 5′ boundary lies between residues 76 and 125, very closely approximating that of the poliovirus IRES

Two-year outcomes of intravitreal aflibercept in a Swiss routine treat and extend regimen for patients with neovascular age-related macular degeneration.

The aim of this observational study was to assess the use and outcome of intravitreal aflibercept in a treat and extend regimen in treatment-naïve neovascular AMD patients in routine practice. This both retrospective and prospective study was conducted in four larger Swiss retina clinics (ASTERIA study). The primary endpoint was the mean change in best-corrected visual acuity (BCVA) in ETDRS letters from baseline to 12 months. Between December 2017 and August 2018, 160 patients were included. For patients with available data, the mean change in BCVA was + 8.4 (± 14.4) letters at month 12 (n = 139) and + 5.0 (± 11.4) letters at month 24 (n = 95). A mean number of 8.3 (± 2.4) injections were administered within the first year and 5.4 (± 2.9) injections during the second year. On average, the observed treatment interval at month 12 was 63.3 (± 22.0) days and increased to 69.1 (± 28.6) days at month 24. For 37% of the patients, a treatment interval ≥ 12 weeks was attained at month 24. In conclusion,  intravitreal aflibercept in a Swiss real-life treat and extend regimen resulted in comparable anatomic and functional outcomes as were observed in the prospective registration trials of aflibercept for nAMD treatment

Effects of sevoflurane and propofol on left ventricular diastolic function in patients with pre-existing diastolic dysfunction.

The effects of anaesthetics on left ventricular (LV) diastolic function in patients with pre-existing diastolic dysfunction are not well known. We hypothesized that propofol but not sevoflurane will worsen the pre-existing LV diastolic dysfunction. Of 24 randomized patients, 23 fulfilled the predefined echocardiographic criterion for diastolic dysfunction. They received general anaesthesia with sevoflurane 1 MAC (n=12) or propofol 4 mug ml(-1) (n=11). Echocardiographic examinations were performed at baseline and in anaesthetized patients under spontaneous breathing and under positive pressure ventilation. Analysis focused on peak early diastolic velocity of the mitral annulus (E(a)). During spontaneous breathing, E(a) was higher in the sevoflurane than in the propofol group [mean (95% CI) 7.0 (5.9-8.1) vs 5.5 (4.7-6.3) cm s(-1); P<0.05], reflecting an increase of E(a) from baseline only in the sevoflurane group (P<0.01). Haemodynamic findings were similar in both groups, but the end-tidal carbon dioxide content was more elevated in the propofol group (P<0.01). During positive pressure ventilation, E(a) was similarly low in the sevoflurane and propofol groups [5.3 (4.2-6.3) and 4.4 (3.6-5.2) cm s(-1), respectively]. During spontaneous breathing, early diastolic function improved in the sevoflurane but not in the propofol group. However, during positive pressure ventilation and balanced anaesthesia, there was no evidence of different effects caused by the two anaesthetics

The flagellin N-methylase gene fliB and an adjacent serovar-specific IS200 element in Salmonella typhimurium

The cloning and molecular genetic analysis of a locus mapping within the flagellar gene (fli) complex of Salmonella typhimurium is reported. A copy of the insertion element IS200 was located in a noncoding stretch of DNA upstream of the fliA gene. Comparative nucleotide sequence analysis showed that this copy of IS200 was 711 bp long and that its flanking regions contained no features common to other characterized insertion sites of this element. The element was located 37 bp downstream of an ORF whose product was shown by interspecific transfer and amino acid analysis to carry out N-methylation of selected lysine residues in Salmonella flagellin. The sequence and phenotype of this ORF identified it as fliB, encoding the only prokaryotic N-methylase acting on amino groups to have been characterized to date. It was found to be conserved among all clinically significant serovars of Salmonella. The IS200 insertion site is of particular interest since it was conserved in all but two rare evolutionary lines of S. typhimurium, and was absent from 85 Salmonella strains belonging to 37 other serovars. It is thus a phylogenetically significant marker at the serovar level.</jats:p

In vitro studies of core peptide‐bearing immunopotentiating reconstituted influenza virosomes as a non‐live prototype vaccine against hepatitis C virus

Evidence from both animal and human viral diseases indicate that cytotoxic T lymphocytes (CTL) are crucial in antiviral defense. However, a major problem to generate cytotoxic immunity is that in vivo exogenous antigens are usually presented via MHC class II pathway and normally fail to induce CTL. The aim of this study is to describe a novel non‐live prototype vaccine based on immunopotentiating reconstituted influenza virosomes (IRIV) as vehicles to deliver HLA‐A*0201‐restricted hepatitis C virus (HCV) peptides (core 35-44 and 131-140) into the cytoplasm of at least three different target cell types [including T2, a transporter associated with antigen processing (TAP)‐deficient cell line] resulting in MHC class I peptide presentation and lysis by peptide‐specific CTL lines. Comparison of kinetics and analysis of the influence of peptide‐stripping and Brefeldin A (BFA) reveal that there exists an endogenous, TAP‐independent and BFA‐sensitive pathway for virosomally delivered peptides. Moreover, virosomes containing influenza matrix peptide 58-66 can efficiently re‐stimulate in vivo primed CTL and, importantly, IRIV containing HCV core peptides can even prime CTL from peripheral blood mononuclear cells of HCV- healthy blood donors in vitro. The fact that in vitro primed CTL are also able to specifically lyse target cells infected with recombinant vaccinia virus encoding the HCV core protein is of great importance for future studies based on in vivo mouse models. One of the most evident advantages of the virosomes in vivo will be their capability to protect the incorporated peptide from a large variety of degrading protease