Lytic Growth of Human Herpesvirus 8: Morphological Aspects

The human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus, is a gamma herpesvirus associated with AIDS-related body cavity-based lymphomas (BCBL), also called primary effusion lymphomas (PEL). These are a rare form of non-Hodgkin lymphomas in which HHV-8 is present, often associated with Epstein-Barr virus (EBV) infection. HHV-8 is also present in a latent state or in a state of low-level persistence in different primary effusion lymphoma-derived cell lines, such BCBL-1 cells, that lack EBV infection. This cell line was induced to produce mature virions by treatment with 12- O -tetradecanoyl phorbol-13-acetate (TPA) and the characteristic ultrastructural features of HHV-8 lytic replication were identified and compared to those of the other members of Herpesviridae family.     

Detection of Epstein–Barr virus‐specific memory CD4+ T cells using a peptide‐based cultured enzyme‐linked immunospot assay

Approaches to evaluate T‐cell responses to Epstein–Barr virus (EBV) include enzyme‐linked immunospot (ELISPOT), which quantifies cells capable of immediate interferon‐γ secretion upon antigen stimulation. However, evaluation of expandable EBV‐specific memory T cells in an ELISPOT format has not been described previously. We quantified EBV‐specific T‐cell precursors with high proliferative capacity by using a peptide‐based cultured interferon‐γ ELISPOT assay. Standard and cultured ELISPOT responses to overlapping peptide pools (15‐mers overlapping by 11 amino acids) covering the lytic (BZLF1 and BMRF1) and latent (EBNA1, EBNA3a, EBNA3b, EBNA3c, LMP1 and LMP2) EBV proteins were evaluated in 20 healthy subjects with remote EBV infection and, for comparison, in four solid organ transplant recipients. Cultured ELISPOT responses to both lytic and latent EBV antigens were significantly higher than standard ELISPOT responses. The distribution of EBV‐specific T‐cell responses detected in healthy virus carriers showed more consistent cultured ELISPOT responses compared with standard ELISPOT responses. T‐cell responses quantified by cultured ELISPOT were mainly mediated by CD4⁺ T cells and a marked pattern of immunodominance to latent‐phase antigens (EBNA1 > EBNA3 family antigens > LMP2 > LMP1) was shown. Both the magnitude and distribution of EBV‐specific T‐cell responses were altered in solid organ transplant recipients; in particular, cultured ELISPOT responses were almost undetectable in a lung‐transplanted patient with EBV‐associated diseases. Analysis of T‐cell responses to EBV by ELISPOT assays might provide new insights into the pathogenesis of EBV‐related diseases and serve as new tools in the monitoring of EBV infection in immunocompromised patients.     

Worrisome Trend of New Multiple Mechanisms of Linezolid Resistance in Staphylococcal Clones Diffused in Italy

In order to assess the frequency of clinically relevant linezolid-resistant staphylococcal isolates, and the role of linezolid in maintaining and coselecting multiple resistance mechanisms (cfr, 23S rRNA, L3/L4 mutations), a prospective Italian study was performed from 2010 to 2011 to confirm the diffusion of three major multidrug-resistant clones (ST2, ST5, ST23).     

Lack of evidence for an association between seminoma and human papillomavirus infection using GP5+/GP6+ consensus primers

Testicular germ cell tumors account for about 1% of all cancers. The incidence of these tumors is increasing and they represent the most common solid malignancies of young men aged 15–40 years with seminoma being one of the most common histotype. Pathogenesis of testicular germ cell tumors remains unknown and, although cryptorchidism is considered the main risk factor, there is evidence of an association with environmental and genetic risk factors. Human papillomaviruses (HPV) are a family of DNA viruses and represent a major risk factor for cervical cancer. In addition, they have been associated with other human non‐malignant and malignant diseases, including breast and head and neck cancer. HPV sequences have been detected throughout the male lower genitourinary tract as well as in seminal fluid and an increased testicular tumorigenesis has been reported in HPV transgenic mice. Aim of this study was to evaluate the potential involvement of HPV in human testicular tumorigenesis. Real‐time PCR employing GP5+/GP6+ consensus HPV primers was used to examine the presence of HPV sequences in a subset of human seminoma (n = 61) and normal testicles (n = 23). None of the specimens tested displayed the presence of HPV DNA. These findings do not support an association between HPV and human seminoma and warrant further studies to assess definitively the role of these viruses in human testicular tumorigenesis. J. Med. Virol. 85:105–109, 2012. © 2012 Wiley Periodicals, Inc.     

Gut microbiota imbalance and chaperoning system malfunction are central to ulcerative colitis pathogenesis and can be counteracted with specifically designed probiotics: a working hypothesis

In this work, we propose that for further studies of the physiopathology and treatment for inflammatory bowel diseases, an integral view of the conditions, including the triad of microbiota–heat shock proteins (HSPs)–probiotics, ought to be considered. Microbiota is the complex microbial flora that resides in the gut, affecting not only gut functions but also the health status of the whole body. Alteration in the microbiota’s composition has been implicated in a variety of pathological conditions (e.g., ulcerative colitis, UC), involving both gut and extra-intestinal tissues and organs. Some of these pathologies are also associated with an altered expression of HSPs (chaperones) and this is the reason why they may be considered chaperonopathies. Probiotics, which are live microorganisms able to restore the correct, healthy equilibrium of microbiota composition, can ameliorate symptoms in patients suffering from UC and modulate expression levels of HSPs. However, currently probiotic therapy follows ex-adiuvantibus criteria, i.e., treatments with beneficial effects but whose mechanism of action is unknown, which should be changed so the probiotics needed in each case are predetermined on the basis of the patient’s microbiota. Consequently, efforts are necessary to develop diagnostic tools for elucidating levels and distribution of HSPs and the microbiota composition (microbiota fingerprint) of each subject and, thus, guide specific probiotic therapy, tailored to meet the needs of the patient. Microbiota fingerprinting ought to include molecular biology techniques for sequencing highly conserved DNA, e.g., genes encoding 16S RNA, for species identification and, in addition, quantification of each relevant microbe.     

Effects of Lactobacillus rhamnosus GG on proliferation and polyamine metabolism in HGC-27 human gastric and DLD-1 colonic cancer cell lines

Previous in vitro and in vivo studies have suggested that lactobacilli can exert antiproliferative effects on the gastrointestinal epithelium. However, their role in affecting the cellular proliferative mechanisms is not completely clear. The aim of this study was to investigate the effects of increasing concentrations of Lactobacillus rhamnosus strain GG (L. GG) homogenate on cell growth and proliferation (by MTT, [³H]-thymidine incorporation and polyamine biosynthesis) in neoplasms originating from different gastrointestinal tracts. Thus, HGC-27 human gastric cancer cells and DLD-1 human colonic adenocarcinoma cells were evaluated. Besides, in order to verify which bacterial fraction was involved in the antiproliferative effects, the cytoplasm and cell wall extracts were tested separately. Gastric HGC-27 and colonic DLD-1 cells showed significant differences in their proliferative behavior, in particular in their polyamine profile and biosynthesis. Notwithstanding, one and the other proved to be sensitive to the growth inhibition by the highest concentrations of bacterial homogenate. Both HGC-27 and DLD-1 cells were resistant to the bacterial cell wall fractions, whereas increasing cytoplasm fraction concentrations induced an evident antiproliferative effect. These data suggest that cytoplasm extracts could be the responsible for L. GG action on proliferation in these two cell lines from gastric and colonic neoplasms.     

Amyloid beta and the longest-lived rodent: the naked mole-rat as a model for natural protection from Alzheimer's disease

Amyloid beta (Aβ) is implicated in Alzheimer's disease (AD) as an integral component of both neural toxicity and plaque formation. Brains of the longest-lived rodents, naked mole-rats (NMRs) approximately 32 years of age, had levels of Aβ similar to those of the 3xTg-AD mouse model of AD. Interestingly, there was no evidence of extracellular plaques, nor was there an age-related increase in Aβ levels in the individuals examined (2–20+ years). The NMR Aβ peptide showed greater homology to the human sequence than to the mouse sequence, differing by only 1 amino acid from the former. This subtle difference led to interspecies differences in aggregation propensity but not neurotoxicity; NMR Aβ was less prone to aggregation than human Aβ. Nevertheless, both NMR and human Aβ were equally toxic to mouse hippocampal neurons, suggesting that Aβ neurotoxicity and aggregation properties were not coupled. Understanding how NMRs acquire and tolerate high levels of Aβ with no plaque formation could provide useful insights into AD, and may elucidate protective mechanisms that delay AD progression.     

Impact of COVID-19 lockdown on sleep quality in university students and administration staff

Journal of Neurology - In Italy, lockdown due to COVID-19 health emergency started on March 10 and partially ended on May 3rd, 2020. There was a significant increase of psychological distress and...     

A Review on Joint Carotid Intima-Media Thickness and Plaque Area Measurement in Ultrasound for Cardiovascular/Stroke Risk Monitoring: Artificial Intelligence Framework

Journal of Digital Imaging - Cardiovascular diseases (CVDs) are the top ten leading causes of death worldwide. Atherosclerosis disease in the arteries is the main cause of the CVD, leading to...