Most of human papilomavirus (HPV) infections are "cleared" by the immune system, however, in case... more Most of human papilomavirus (HPV) infections are "cleared" by the immune system, however, in cases of immune system suppression infections could lead to development of malignancies. The aim of this study was to find out the frequency of HR-HPV infection in early period after renal transplantation in recipients receiving immunosuppressive therapy and to follow the progression of the infection up to one year. METHODS: 43 female renal transplant recipients and 79 healthy female individuals as a control group were enrolled in this investigation. For the detection of HPV infection patients' samples (blood and vaginal swabs) where collected two weeks after transplantation with following collection of six months and one year. Different polymerase chain reactions for HR-HPV genomic sequences detection and ELISA kit for detection of anti-HPV IgG antibodies were used. RESULTS: In this study we show that frequency rate of HR-HPV infection has increased by the one year after transplantation from early stage of immunosuppressive therapy (from 24% to 36%). Also an increase of HR-HPV load was detected over time, showing the highest median viral load at sixth month after transplantation. CONCLUSIONS: From the obtained data, it follows that it is very important to carefully monitor patients receiving immunosuppression therapy on progression of HR-HPV.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
The majority of the studies where the antisense approach has been used to inhibit retroviral infe... more The majority of the studies where the antisense approach has been used to inhibit retroviral infection deal with the antiviral activity of antisense (as) nucleic acids [3, 4, 18, 2125]. The transfer into cells of as-genes complementary to functionally important regions of a viral genome confers intracellular immunity to the corresponding virus. Gene engineering allows constructions of as-genes complementary to practically any viral gene, and effective promoter systems ensure high levels of as-gene expression. Our previous studies [16, 26] demonstrated that BLV replication in chronically infected FLK cells is inhibited by as-nucleic acids targeted at LTR R-U5 and pX regions of the viral genome. The functions of as-nucleic acids in gene regulation strongly depend on the target sequences selected in the viral genome. Our studies [26], as well as the observations of [3, 4], showed that the
Proceedings of the Latvian Academy of Sciences. Section B, Natural, Exact and Applied Sciences, Aug 1, 2016
Human herpesvirus-6 (HHV-6) is a ubiquitous betaherpesvirus with immunomodulating properties that... more Human herpesvirus-6 (HHV-6) is a ubiquitous betaherpesvirus with immunomodulating properties that have been suggested to play an important role in the development of several autoimmune disorders. Although the primary targets for HHV-6 replication, both in vitro and in vivo, are CD4+ and CD8+ T lymphocytes, some studies have reported the presence of HHV-6 sequences in different solid organs, including in the thyroid gland, showing possible involvement of this herpesvirus in development of autoimmune thyroid disease. The aim of this study was to determine loads of HHV-6 in thyroid gland tissue in comparison to those in peripheral blood of patients with autoimmune thyroiditis. Seven patients [women mean age 45 (28-65)] with histologically confirmed autoimmune thyroiditis were enrolled in this study. Fluorescence-activated cell sorting was used to distinguish and sort lymphocyte populations from peripheral blood mononuclear cells of patients. HHV-6 load was determined by real-time PCR for peripheral blood and thyroid gland tissue samples. Additionally, all results from molecular analyses were compared with histological results obtained by light microscopy. Viral load was detected only in one (46 viral copies/ 1×10 6 cells) blood sample; others were under the detection limit of the used kit. However, in all HHV-6 positive tissue samples viral load was detected in the range of 132-1620 viral copies/10 6 cells. Substantial HHV-6 load in lymphocyte subpopulations was detected in two of seven patients. HHV-6 load was detected in NK and CD95 + cells of two patients. The obtained results show that thyroid gland cells (tyrocytes) act as target cells for HHV-6.
Progressive multifocal leukoencephalopathy (PML) is a neurological disease caused by infection of... more Progressive multifocal leukoencephalopathy (PML) is a neurological disease caused by infection of the central nervous system (CNS) with the JC polyomavirus (JCV). JCV is endemic and infects a large proportion (70-90%) of healthy individuals worldwide, but infection is latent. JCV reactivation may occur, if the immune function is compromised. Aim: To present a PML case in a CLL patient after a long course of disease and treatment with fludarabine. JCV virus infection in this patient was proven both in brain biopsy material and blood. Methods: Patient with a nine-year history of CLL was hospitalized with the weakness in the right leg and left hand, tremors, speech difficulties. An MRI diagnosed infiltrative glial tumor of the left hemisphere, proliferating predominantly in the frontal lobe, more in the gyrus frontalis superior region. CNS tumor biopsy performed. Results: Morphology and immunoprofile of the lesion consistent with progressive multifocal leukoencephalopathy. The material from biopsy was diagnosed as positive for JCV DNA. JCV and HHV-7 genomic sequences were found in patient's PBL DNA sample. In a plasma DNA sample, only genomic sequences were detected. Conclusion: The present case draws attention to the fact that the use of fludarabine and its combinations in CLL therapy increases the risk of JCV infection reactivation and development of serious complications like PML.
Parvovirus B19 infection increases proliferative activity of non-permissive cells
ABSTRACT Parvovirus B19 (B19) is associated with a wide spectrum of diseases in humans, including... more ABSTRACT Parvovirus B19 (B19) is associated with a wide spectrum of diseases in humans, including autoimmune disorders and is possibly involved in the pathogenesis of some carcinomas. The appearance of B19 infection in non-permissive cells is poorly explored. Our study demonstrates that B19 virus is able to infect epithelial-like HOS TE85 cells. Although the virus particles were not found, the virus genomic DNA was detected in HOS cells during 3-11 passages. Moreover, the expression of B19 VP1 and NS1 mRNAs and the presence VP1/VP2 proteins were revealed in infected cells. The manifestation of B19 infection was dependent on virus dose. At the high dose (5000-8000 virus genomes/cell) massive apoptosis developed on the 6th day after infection and the cells were lost. Morphological and electron microscopy studies showed that the cytopathic effect was associated with apoptotic alteration in HOS cells. At the lower virus dose (100-1000 virus genomes/cell) the B19 infection in HOS cells was accompanied by a 1.5-1.8 times elevated IL-6 level and by 1.5-1.9 times increased proliferative activity of the infected cells. An intact VP1 unique region and a VP1u with a point mutation in the sPLA(2) catalytic site were expressed in E. coli. The intact VP1u protein increased the cells proliferative activity by up to 2-3.5 times in a dose-dependent manner while mutated sPLA2 deficient VP1u had no effect on the cell proliferation. We suggest that the stimulation of the cells' proliferation is associated with phospholipase A(2)activity of B19 capside protein VP1.
1071 (IDO1) expression was analysed by Western Blot and expression of enzymes of the kynurenine p... more 1071 (IDO1) expression was analysed by Western Blot and expression of enzymes of the kynurenine pathway by real-time PCR. Tryptophan/ kynurenine levels in culture supernatants were quantified by HPLC. Results: SF strongly inhibited the proliferation of co-cultured Th cells. Tryptophan was completely depleted within a few days in co-cultures of SF and Th cells, resulting in eukaryotic initiation factor (eIF)2α phosphorylation, TCRζ-chain downregulation and proliferation arrest. Blocking of IDO1 completely restored Th cell proliferation, indicating that SF suppressed the proliferation of Th cells through IDO1-mediated tryptophan catabolism. Interestingly, RASF showed a significantly lower IDO1 expression, tryptophan metabolism and a weaker Th cell suppressive capacity compared to OASF. Under hypoxic conditions, the secretion of IFNg, the expression of IDO1, the tryptophan metabolism and the Th cell suppressive capacity of both OASF and RASF were significantly reduced. Conclusions: SF suppressed Th cell growth through IDO1-mediated tryptophan catabolism. This mechanism may play an important role in preventing inappropriate Th cell responses under normal conditions. The reduced tryptophan metabolism under hypoxia together with the inferior efficiency of RASF to restrict T cell proliferation likely supports the development of synovitis in RA.
Background The aim of this study was to explore the tolerability and effect of static stretching ... more Background The aim of this study was to explore the tolerability and effect of static stretching (SS) and whole body cryotherapy (WBC) upon fatigue, daytime sleepiness, cognitive functioning and objective and subjective autonomic nervous system functioning in those with Chronic Fatigue Syndrome (CFS) compared to a control population. Methods Thirty-two CFS and eighteen healthy controls (HC) participated in 2 weeks of a SS + WBC programme. This programme was composed of five sessions per week, 10 sessions in total. Results A significant decrease in fatigue was noted in the CFS group in response to SS + WBC. Some domains of cognitive functioning (speed of processing visual information and set-shifting) also improved in response to SS + WBC in both CFS and HC groups. Our study has confirmed that WBC is well tolerated by those with CFS and leads to symptomatic improvements associated with changes in cardiovascular and autonomic function. Conclusions Given the preliminary data showing th...
Результаты хирургической коррекции врожденного псевдоартроза большеберцовой кости в зависимости от активации вирусной инфекции HHV-6/HHV-7 у ребенка с нейрофиброматозом 1-го типа
Neurofibromatosis type-1 (NF-1) — is a common genetic disease effecting the skin, subcutaneous ti... more Neurofibromatosis type-1 (NF-1) — is a common genetic disease effecting the skin, subcutaneous tissue peripheral nerves and bones (tibia pseudarthrosis). Immunomodulatory viruses HHV-6 and HHV-7 are classifying as a genus of roseoloviruses of subfamily β-herpesviruses. Reactivation of HHV-6 and HHV-7 inhibits immune system and indirectly promote to other infectious agents. The article deals with a unique case repot of two repeated transplantations of fibula due to congenital tibia pseudarthrosis caused by NF-1. Results of the transplantations, related to active and latent HHV-6 and HHV-7 infection in a 6 years old child are discussed in the paper.
In this study we set out to define the characteristics of autonomic subgroups of patients with Ch... more In this study we set out to define the characteristics of autonomic subgroups of patients with Chronic Fatigue Syndrome (CFS). The study included 131 patients with CFS (Fukuda criteria). Participants completed the following screening symptom assessment tools: Chalder Fatigue Scale, Fatigue Impact Scale, Fatigue Severity Scale, Epworth Sleepiness Scales, the self-reported Composite Autonomic Symptom Scale. Autonomic parameters were measured at rest with a Task Force Monitor (CNS Systems) and arterial stiffness using an Arteriograph (TensioMed Kft.). Principal axis factor analysis yielded four factors: fatigue, subjective and objective autonomic dysfunction and arterial stiffness. Using cluster analyses, these factors were grouped in four autonomic profiles: 34% of patients had sympathetic symptoms with dysautonomia, 5% sympathetic alone, 21% parasympathetic and 40% had issues with sympathovagal balance. Those with a sympathetic-dysautonomia phenotype were associated with more severe ...
SAT0339 Virologic and Morphologic Evidences of Human Parvovirus B19 Infection in Osteoarthritis
Annals of the Rheumatic Diseases, 2013
ABSTRACT Background Viral infections play a role in the pathogenesis of various forms of osteoart... more ABSTRACT Background Viral infections play a role in the pathogenesis of various forms of osteoarthritis (OA). The advanced stage of disease often manifests with severe inflammation and lesions of joint tissues related to the parvovirus B19 (B19) infection. Objectives This study aimed to demonstrate the spectra of synovial and supporting tissue damage in OA patients in association with the presence of B19 infection markers. Methods 60 OA patients and 27 age and gender matched practically healthy persons were enrolled in this study and peripheral blood (PB) samples collected. RecomLine test was used to detect of B19-specific antibodies, nPCR – to detect virus-specific sequences, proliferation test – to detect T-lymphocytes’ response to B19 antigens. From 30OA patients synovial, cartilaginous and osseous samples were obtained and conventionally processed for histopathology. B19 capsid proteins’ VP1/VP2 expression and joint tissue remodeling was assessed by immunohistochemistry, COX2 mRNA expression – by RT-PCR. Results Application of serological, molecular and immunohistochemical techniques sets up the presence of greatly varying results. No difference in the B19 specific IgG antibodies’ prevalence was found between OA patients and control group persons (83.3 and 76%, respectively), however antibodies to B19 NS1 were detected in 41.7% of OA patients vs. 3.7% of healthy persons. Anti-B19 IgM antibodies were revealed in OA patients significantly more often (30.5 vs. 8% in healthy persons). In peripheral blood/plasma DNA of 11 OA patients (18.3%) B19 genomic sequences were found. B19 sequences in PB leukocytes’ DNA were detected in OA patients only (7.7%). T-lymphocytes of OA patients responded to B19 antigens with proliferation more often and faster than control group persons confirming chronic activation of the first ones. Findings of B19 specific sequences in OA patients’ synovial tissues DNA were not unequivocal. B19 capsid protein expression was demonstrated in OA patients’ synovial, cartilaginous and osseous tissues. The red bone marrow erythroblasts, monocytes, megakaryocytes and endothelial cells showed affection evidenced by anti-B19 immunostaining. Inflammatory cells of synovial infiltrates also displayed the immunopositivity. The damage and remodeling of joint tissue was evidenced by strong immunoexpression of metalloproteinase-9 and transforming growth factor-beta found in the spongy bone, articular cartilage and synovial membrane compartments. In synovial tissues of OA patients with plasma viremia two times higher COX2 mRNA expression was shown in comparison with OA patients without viremia. Conclusions We suggest that B19 infection may contribute to the inflammatory and structural damage in the advanced stage of OA. The results proved by application of serological and molecular biological B19 infection markers should not be considered solely. These findings should be jointly implemented by immunohistochemistry data reflecting the local tissue damage and contribution of B19 to OA. Disclosure of Interest None Declared
Review | patient advocate was formed with the purpose of developing criteria based on current kno... more Review | patient advocate was formed with the purpose of developing criteria based on current knowledge. Thirteen countries and a wide range of specialties were represented. Collectively, members have approximately 400 years of both clinical and teaching experience, authored hundreds of peer-reviewed publications, diagnosed or treated approximately 50 000 patients with ME, and several members coauthored previous criteria. The expertise and experience of the panel members as well as PubMed and other medical sources were utilized in a progression of suggestions ⁄ drafts ⁄ reviews ⁄ revisions. The authors, free of any sponsoring organization, achieved 100% consensus through a Delphi-type process. The scope of this paper is limited to criteria of ME and their application. Accordingly, the criteria reflect the complex symptomatology. Operational notes enhance clarity and specificity by providing guidance in the expression and interpretation of symptoms. Clinical and research application guidelines promote optimal recognition of ME by primary physicians and other healthcare providers, improve the consistency of diagnoses in adult and paediatric patients internationally and facilitate clearer identification of patients for research studies.
Показана экспрессия антисмыслоеых (ас) по отношению к LTR BLV (район 341в !в п. н.) и гену X BLV ... more Показана экспрессия антисмыслоеых (ас) по отношению к LTR BLV (район 341в !в п. н.) и гену X BLV (район 6497-7929 п. н.) последовательностей в клонах культе рік клеток FLK, персистентно продуцирующих BLV. Выявленная экспрессия ас-последовательностей согласуется со снижением РНК-зависимой ДНК-полимеразной активности, концентрации главного внутреннего белка BLV р24 и продукции вирионов.
Background: Survival of oropharyngeal squamous cell carcinoma (OSCC) patients depends on the risk... more Background: Survival of oropharyngeal squamous cell carcinoma (OSCC) patients depends on the risk and environmental factors, tumor biology, achievements in diagnostics and treatment approaches. Aim: To perform a survival analysis of the patients with OSCC treated over a 10-year period in a single hospital in Latvia linking these data to histopathological findings, risk factors and received therapy. Materials and Methods: The main outcome measures were overall and disease-specific survival (OS and DS) along with histopathology analysis. Results: Kaplan-Meier survival analysis showed better survival for females, younger patients lacking bad habits, operated and received radiotherapy, with lower T grade and disease stage. Cox regression showed diminished early death risk in patients with lower T grade, no regional metastases (N0) and bad habits, operated and received radiotherapy. A vast majority of tumors were localized in palatine tonsils and the base of the tongue. The localization did not correlate with mean survival time/survival. Lower OS (p = 0.03) and DS (p = 0.026) were estimated for patients with pharyngeal wall and tonsillar involvement compared to tumors localized in the soft palate. A histological variant of tumor seemed irrelevant estimating OS and DS, whereas therapeutic modalities significantly affected survival. Conclusions: OSCC patients with lower T grade, N0 status, lacking bad habits, and surgically treated had better survival.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
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