Browsing by Author "Groma, Valerija"
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Item Analysis of the occurrence and distribution of primary and recurrent basal cell carcinoma of head and neck coupled to the assessment of tumor microenvironment and Sonic hedgehog signaling(2020) Moisejenko-Golubovica, Jelena; Volkov, Oleg; Ivanova, Anna; Groma, Valerija; Rīga Stradiņš University; Institute of Anatomy and AnthropologyOften, basal cell carcinoma (BCC) displays local aggressiveness, and when developed in the head and neck presents with deep tissue invasion and recurrence. Previous studies have pointed out the necessity of systematic assessment of primary and recurrent BCC based on a better understanding of the biology and function of its microenvironment. Although hedgehog-dependent tumor cells signaling to the underlying stroma, and vice versa, have been demonstrated to be implicated in the pathogenesis of BCC, little is known about peculiarities of the tumor microenvironment and the above-mentioned signaling in the head and neck. The occurrence and distribution of 79 primary and recurrent BCCs developed in the head and neck region were estimated. The data were coupled with the immunohistochemical assessment of type IV collagen, laminin, alpha-smooth muscle actin (α-SMA), and Sonic hedgehog (Shh). The frequency of the mixed BCCs and the predominance of the nose and cheek region affection by primary and recurrent tumors were demonstrated. Furthermore, the increase of peritumoral and entire stromal α-SMA immunoreactivity in the mixed recurrent BCC was confirmed using statistics. We found the increase of strong levels of Shh immunoexpression in the aggressive variants of BCC - infiltrative, mixed, and micronodular. Surprisingly, we confirmed the upregulation of Shh paralleled by the downregulation of α-SMA immunoexpression in the superficial subtype of the tumor. Our results suggest the necessity of further studies assessing the nature of the tumor along with the peculiarities of signaling in BCCs of head and neck.Item Comparison of outcome between blood culture positive and negative infective endocarditis patients undergoing cardiac surgery(2021-05-27) Meidrops, Kristians; Zuravlova, Arina; Osipovs, Janis Davis; Kalejs, Martins; Groma, Valerija; Petrosina, Eva; Reinis, Aigars; Strike, Eva; Dumpis, Uga; Erglis, Andrejs; Stradins, Peteris; Rīga Stradiņš University; Statistics Unit; Department of Biology and MicrobiologyBackground: Up to 30% or even more of all infective endocarditis (IE) cases are recognized as blood culture negative, meaning that the causative agent is left unidentified. The prompt diagnosis together with the identification of causative microorganism and targeted antibiotic treatment can significantly impact the prognosis of the disease and further patient’s health status. In some studies, blood culture negative endocarditis has been shown to be associated with delayed diagnosis, worse outcome and course of the disease, and a greater number of intra and postoperative complications. Methods: We retrospectively analysed the medical records of all patients who underwent cardiac surgery for endocarditis between years 2016 and 2019. The aim of this study was to analyse short and long-term mortality and differences of laboratory, clinical and echocardiography parameters in patients with blood culture positive endocarditis (BCPE) and blood culture negative endocarditis (BCNE) and its possible impact on the clinical outcome. Results: In our study population were 114 (55.1%) blood culture positive and 93 (44.9%) blood culture negative cases of infectious endocarditis. The most common pathogens in the blood culture positive IE group were S.aureus in 36 cases (31.6%), Streptococcus spp. in 27 (23.7%), E.faecalis in 24 (21.1%), and other microorganisms in 27 (23.7%). Embolic events were seen in 60 patients (28.9%). In univariate analyses, detection of microorganism, elevated levels of procalcitonin were found to be significantly associated with intrahospital death, however it did not reach statistical significance in multivariate analyses. Among microorganisms, S.aureus was significantly associated with intrahospital death in both univariate and multivariate analyses. Conclusions: There are no statistically significant differences between groups of BCPE and BCNE in terms of intrahospital mortality, hospital and ICU stay or 3-year mortality. There were higher levels of procalcitonin in BCPE group, however procalcitonin failed to show independent association with mortality in multivariate analysis. The most common microorganism in the BCPE group was S.aureus. It was associated with independently higher intrahospital mortality when compared to other causative microorganisms.Item Effect of Human Herpesviruses 6 and 7 Infection on the Clinical Course of Rheumatoid Arthritis(2016-08-01) Kadiša, Anda; Nora-Krūkle, Zaiga; Kozireva, Svetlana; Svirskis, Simons; Studers, Peteris; Groma, Valerija; Lejnieks, Aivars; Murovska, Modra; Department of Internal Diseases; Institute of Microbiology and Virology; Joint Laboratory of Traumatology and Orthopaedics; Institute of Anatomy and AnthropologyRheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease affecting joints and causing symmetrical chronic progressive aseptic synovitis and erosive-destructive changes. Viruses and viral infections are considered to be the main risk factors for autoimmune disease development (especially for individuals with genetic predisposition). The goal of this study was to evaluate the frequency of HHV-6 and HHV-7 persistent infection and its activity phase in RA and osteoarthritis (OA) patients, and healthy persons. We examined also the influence of HHV-6 and-7 infections on RA activity, aggressiveness, radiographical stage, and frequency of complications as well as the presence of HHV-6 infection markers in synovial fluid and synovial tissues of RA joints of affected patients. Despite the lack of significant correlation between frequency of persistent single HHV-6, single HHV-7, and concurrent HHV-6 and HHV-7 infection and RA clinical course, we found that both active and latent HHV-6 and/or HHV-7 infection increased RA activity and progression in several clinical and laboratory parameters. Regarding the severity of the course of RA, we observed also a high prevalence of RA complications in the patient group with active single HHV-6 infection and also a more severe radiographical stage in RA patients with active concurrent HHV-6 and HHV-7 infection. Moreover, viral infection markers were found in synovial fluid and synovial tissues of affected joints of RA patients. This suggests that HHV-6 and/or HHV-7 infection has effect on the disease clinical course, but virus reactivation may be a consequence of immunosuppressive treatment.Item Effect of infliximab induction therapy on secondary systemic amyloidosis associated with Crohn's disease : Case report and review of the literature(2013-09) Pukitis, Aldis; Zake, Tatjana; Groma, Valerija; Ostrovskis, Evalds; Skuja, Sandra; Pokrotnieks, Juris; Institute of Anatomy and Anthropology; Department of Internal DiseasesSecondary systemic (AA) amyloidosis is reported as a serious complication that occurs in long-standing Crohn's disease (CD), with an incidence of 0.3-10.9%. Various therapeutic approaches using medicines and elemental diet have been recomended, but still there are no established standards of treatment for secondary systemic amyloidosis in CD. Only a few studies have shown the role of TNFα ihibitors in the treatment of AA amyloidosis over a long term period. We report the case of a 24-year-old male with CD complicated by AA amyloidosis with renal and gastrointestinal tract involvement treated with infliximab as induction therapy. Intestinal AA amyloidosis progression occurred at the same time with the development of CD as an early complication, whereas duration of CD prior to the diagnosis of renal AA amyloidosis was 6 years. Infliximab therapy (3 infusions) caused a significant decrease of serum amyloid A protein (by 97.9%), C-reactive protein (by 70%), improvement of disease activity index, and CD caused clinical symptoms. At the same time gradual progression of the renal damage (reduction of renal function) was not affected by the treatment. Direct efficacy of infliximab infusions on serum amyloid protein level may support the hypothesis of TNFα induced reduction on the progression of AA amyloidosis described in previous study reports. Targeted histological analysis of tissue biopsy is crucial to clarify the presence of AA amyloidosis in CD induced multiorgan damage cases.Item Evidence of human parvovirus B19 infection in the post-mortem brain tissue of the elderly(2018-11) Skuja, Sandra; Vilmane, Anda; Svirskis, Simons; Groma, Valerija; Murovska, Modra; Institute of Anatomy and Anthropology; Institute of Microbiology and VirologyAfter primary exposure, the human parvovirus B19 (B19V) genome may remain in the central nervous system (CNS), establishing a lifelong latency. The structural characteristics and functions of the infected cells are essential for the virus to complete its life cycle. Although B19V has been detected in the brain tissue by sequencing PCR products, little is known about its in vivo cell tropism and pathogenic potential in the CNS. To detect B19V and investigate the distribution of its target cells in the CNS, we studied brain autopsies of elderly subjects using molecular virology, and optical and electron microscopy methods. Our study detected B19V in brain tissue samples from both encephalopathy and control groups, suggesting virus persistence within the CNS throughout the host’s lifetime. It appears that within the CNS, the main target of B19V is oligodendrocytes. The greatest number of B19V-positive oligodendrocytes was found in the white matter of the frontal lobe. The number was significantly lower in the gray matter of the frontal lobe (p = 0.008) and the gray and white matter of the temporal lobes (p < 0.0001). The morphological changes observed in the encephalopathy group, propose a possible B19V involvement in the demyelination process.Item Heterogeneity of tissue IL-17 and tight junction proteins expression demonstrated in patients with autoimmune thyroid diseases(2018-06-01) Zake, Tatjana; Skuja, Sandra; Kalere, Ieva; Konrade, Ilze; Groma, Valerija; Department of Internal Diseases; Institute of Anatomy and AnthropologyTh17 cells together with their hallmark cytokine interleukin (IL)-17 were identified as crucial contributing factors in the pathogenesis of thyroid autoimmunity. The cytokine-regulated tight junction (Tj) disruption is thought to be essential in the initiation and/or development of several diseases. Still, the role of IL-17 maintaining Tj integrity in autoimmune thyroid diseases (AITDs) has not yet been evaluated. We aimed to investigate integrity of the thyroid follicle by studying immunoexpression of cellular Tj - zonula occludens (ZO)-1 and claudin-1 proteins coupled to IL-17A and CD68 detection in AITD patients compared with controls. Thirty-five adult patients undergoing thyroidectomy and presenting 18 cases of Hashimoto thyroiditis (HT), 7 of Graves' disease (GD) as well as 10 subjects of colloid goiter without autoimmune component served as controls were enrolled in this study. An immunohistochemical analysis including IL-17A, ZO-1, claudin-1, and CD68 detection was performed in each case. The correlation of IL-17A with Tj and CD68 in patients with AITD was also analyzed. Apart from inflammatory cells, we evidenced a stronger expression level of IL17A in the thyroid follicular cells in HT patients when compared with GD or colloid goiter. A significant reduction of ZO-1 immunoreactivity was observed in the thyrocytes in HT patients, whereas no significant differences were found in claudin-1 expression in HT and GD compared with colloid goiter patients. A significantly higher number of thyroid follicles with CD68-positive cells was found in HT patients than that in patients with GD or colloid goiter. In HT patients, the expression of IL-17A in the follicular cells was positively correlated with CD68 immunopositivity, whereas no association with claudin-1 or ZO-1 expression was found. GD patients did not reveal any significant correlation of IL-17A with Tj and CD68. Strong overexpression of IL-17A observed in the thyroid epithelial cells is associated with the presence of intrafollicular CD68-positive cells in HT patients. We evidenced the changes in molecules of thyrocyte junctional complexes highlighting impairment of the thyroid follicle integrity in HT, but no association with IL-17A was found.Item Identification of High-Risk Human Papillomavirus DNA, p16, and E6/E7 Oncoproteins in Laryngeal and Hypopharyngeal Squamous Cell Carcinomas(2021-06) Lifsics, Andrejs; Groma, Valerija; Cistjakovs, Maksims; Skuja, Sandra; Deksnis, Renars; Murovska, Modra; Department of Otorhinolaryngology; Institute of Anatomy and Anthropology; Institute of Microbiology and VirologyHuman papillomavirus (HPV) was proven to play a significant role in cancer development in the oropharynx. However, its role in the development of laryngeal (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC) remains to be clarified. High-risk HPV (HR-HPV) viral proteins E6 and E7 are considered to be pertinent to HPV-related carcinogenesis. Hence, our aim was to estimate LSCC and HPSCC for HR-HPV DNA, p16, and E6/E7 oncoprotein status by using molecular virology and immunohistochemistry methods. The prevalence of HPV16 infection was 22/41 (53.7%) and 20/31 (64.5%) for LSCC and HPSCC, accordingly. The majority of HPV16+ tumor samples were stage III or IV. In most samples, the presence of either HPV16 E6 or HPV16 E7 viral protein in dysplastic or tumor cells was confirmed using immunohistochemistry. Our results suggest a high prevalence of HPV16 as a primary HR-HPV type in LSCC and HPSCC. The lack of HPV E6/E7 oncoproteins in some tumor samples may suggest either the absence of viral integration or the presence of other mechanisms of tumorigenesis. The utilization of p16 IHC as a surrogate marker of HR-HPV infection is impractical in LSCC and HPSCC.Item Immunological mechanisms of autoimmune thyroid diseases : A shift in the traditional TH1/TH2 paradigm(2019-05-01) Zaķe, Tatjana; Skuja, Sandra; Lejnieks, Aivars; Groma, Valerija; Konrade, Ilze; Institute of Anatomy and Anthropology; Department of Internal DiseasesAutoimmune thyroid diseases (AITD) mainly include Hashimoto's thyroiditis (HT) and Graves' disease (GD), which are characterised by the presence of circulating antibodies against various thyroid autoantigens and infiltration of the thyroid gland by autoreactive lymphocytes. Despite the significant advancement in the knowledge of AITD pathogenesis in the last decade, the specific immunological mechanisms responsible for development of the disease are not thoroughly understood. Classically, HT has long been considered as a T helper (Th)1-mediated disease, while a Th2-driven autoimmune response is dominant for GD development. However, this classification has changed due to the description of Th17 lymphocytes, which suggested participation of these cells in AITD, particularly HT pathogenesis. Moreover, a shift in the balance between Th17 and T regulatory (Treg) cells has been observed in thyroid autoimmunity. We have observed overexpression of IL-17, the prominent effector cytokine of Th17, within thyroid tissues from HT and GD patients in our studies. The present review will focus on recent data regarding the role of Treg and Th17 lymphocytes in AITD pathogenesis. In addition, the impact and proposed mechanisms of the predominant environmental factors triggering the autoimmune response to the thyroid will be discussed.Item Inflammatory Cytokine-Producing Cells and Inflammation Markers in the Synovium of Osteoarthritis Patients Evidenced in Human Herpesvirus 7 Infection(2020) Groma, Valerija; Tarasovs, Mihails; Skuja, Sandra; Semenistaja, Sofija; Nora-Krukle, Zaiga; Svirskis, Simons; Murovska, ModraA direct association between joint inflammation and the progression of osteoarthritis (OA) has been proposed, and synovitis is considered a powerful driver of the disease. Among infections implicated in the development of joint disease, human herpesvirus 7 (HHV-7) infection remains poorly characterized. Therefore, we assessed synovitis in OA patients; determined the occurrence and distribution of the HHV-7 antigen within the synovial membrane of OA-affected subjects; and correlated plasma levels of the pro-inflammatory cytokines tumor necrosis factor (TNF), interleukin-6 (IL-6), and TNF expressed locally within lesioned synovial tissues with HHV-7 observations, suggesting differences in persistent latent and active infection. Synovial HHV-7, CD4, CD68, and TNF antigens were detected immunohistochemically. The plasma levels of TNF and IL-6 were measured by an enzyme-linked immunosorbent assay. Our findings confirm the presence of persistent HHV-7 infection in 81.5% and reactivation in 20.5% of patients. In 35.2% of patients, virus-specific DNA was extracted from synovial membrane tissue samples. We evidenced the absence of histopathologically detectable synovitis and low-grade changes in the majority of OA patients enrolled in the study, in both HHV-7 PCR+ and HHV-7 PCR‒ groups. The number of synovial CD4-positive cells in the HHV-7 polymerase chain reaction (PCR)+ group was significantly higher than that in the HHV-7 PCR‒ group. CD4- and CD68-positive cells were differently distributed in both HHV-7 PCR+ and HHV-7 PCR‒ groups, as well as in latent and active HHV-7 infection. The number of TNF+ and HHV-7+ lymphocytes, as well as HHV-7+ vascular endothelial cells, was strongly correlated. Vascular endothelial cells, especially in the case of infection reactivation, appeared vulnerable. The balance between virus latency and reactivation is a long-term relationship between the host and infectious agent, and the immune system appears to be involved in displaying overreaction when a shift in the established equilibrium develops.Item Inflammatory cytokine-producing cells and inflammation markers in the synovium of osteoarthritis patients evidenced in human herpesvirus 7 infection(2020-09-01) Groma, Valerija; Tarasovs, Mihails; Skuja, Sandra; Semenistaja, Sofija; Nora-Krukle, Zaiga; Svirskis, Simons; Murovska, Modra; Joint Laboratory of Electron Microscopy; Institute of Anatomy and Anthropology; Department of Internal Diseases; Institute of Microbiology and VirologyA direct association between joint inflammation and the progression of osteoarthritis (OA) has been proposed, and synovitis is considered a powerful driver of the disease. Among infections implicated in the development of joint disease, human herpesvirus 7 (HHV-7) infection remains poorly characterized. Therefore, we assessed synovitis in OA patients; determined the occurrence and distribution of the HHV-7 antigen within the synovial membrane of OA-affected subjects; and correlated plasma levels of the pro-inflammatory cytokines tumor necrosis factor (TNF), interleukin-6 (IL-6), and TNF expressed locally within lesioned synovial tissues with HHV-7 observations, suggesting differences in persistent latent and active infection. Synovial HHV-7, CD4, CD68, and TNF antigens were detected immunohistochemically. The plasma levels of TNF and IL6 were measured by an enzyme-linked immunosorbent assay. Our findings confirm the presence of persistent HHV-7 infection in 81.5% and reactivation in 20.5% of patients. In 35.2% of patients, virusspecific DNA was extracted from synovial membrane tissue samples. We evidenced the absence of histopathologically detectable synovitis and low-grade changes in the majority of OA patients enrolled in the study, in both HHV-7 PCR+ and HHV-7 PCR‒ groups. The number of synovial CD4positive cells in the HHV-7 polymerase chain reaction (PCR)+ group was significantly higher than that in the HHV-7 PCR‒ group. CD4-and CD68-positive cells were differently distributed in both HHV-7 PCR+ and HHV-7 PCR‒ groups, as well as in latent and active HHV-7 infection. The number of TNF+ and HHV-7+ lymphocytes, as well as HHV-7+ vascular endothelial cells, was strongly correlated. Vascular endothelial cells, especially in the case of infection reactivation, appeared vulnerable. The balance between virus latency and reactivation is a long-term relationship between the host and infectious agent, and the immune system appears to be involved in displaying overreaction when a shift in the established equilibrium develops.Item Low cardiac content of long-chain acylcarnitines in TMLHE knockout mice prevents ischaemia-reperfusion-induced mitochondrial and cardiac damage(2021-12) Liepinsh, Edgars; Kuka, Janis; Vilks, Karlis; Svalbe, Baiba; Stelfa, Gundega; Vilskersts, Reinis; Sevostjanovs, Eduards; Goldins, Niks Ricards; Groma, Valerija; Grinberga, Solveiga; Plaas, Mario; Makrecka-Kuka, Marina; Dambrova, Maija; Rīga Stradiņš UniversityIncreased tissue content of long-chain acylcarnitines may induce mitochondrial and cardiac damage by stimulating ROS production. N6-trimethyllysine dioxygenase (TMLD) is the first enzyme in the carnitine/acylcarnitine biosynthesis pathway. Inactivation of the TMLHE gene (TMLHE KO) in mice is expected to limit long-chain acylcarnitine synthesis and thus induce a cardio- and mitochondria-protective phenotype. TMLHE gene deletion in male mice lowered acylcarnitine concentrations in blood and cardiac tissues by up to 85% and decreased fatty acid oxidation by 30% but did not affect muscle and heart function in mice. Metabolome profile analysis revealed increased levels of polyunsaturated fatty acids (PUFAs) and a global shift in fatty acid content from saturated to unsaturated lipids. In the risk area of ischemic hearts in TMLHE KO mouse, the OXPHOS-dependent respiration rate and OXPHOS coupling efficiency were fully preserved. Additionally, the decreased long-chain acylcarnitine synthesis rate in TMLHE KO mice prevented ischaemia-reperfusion-induced ROS production in cardiac mitochondria. This was associated with a 39% smaller infarct size in the TMLHE KO mice. The arrest of the acylcarnitine biosynthesis pathway in TMLHE KO mice prevents ischaemia-reperfusion-induced damage in cardiac mitochondria and decreases infarct size. These results confirm that the decreased accumulation of ROS-increasing fatty acid metabolism intermediates prevents mitochondrial and cardiac damage during ischaemia-reperfusion.Item Plexus brachialis strain and compression deformation in the costo-axillary-brachial region : A cadaveric study(2011) Vasilevskis, Edgars; Skuja, Sandra; Evansa, Irina; Šteina, Eva; Pilipa, Anna Sondore; Vabels, Grigorijs; Teibe, Uldis; Jansons, Haralds; Groma, Valerija; Vanags, Indulis; Rīga Stradiņš University; Department of Morphology; Department of Anaesthesiology, Intensive Care and Clinical simulationsObjective: The aim of this study was to clarify the role of different mechanisms in nerve injury during arm abduction positions. The tasks were to determine the strain deformation of the plexus brachialis during arm abduction, to measure the pressures in the neurovascular bundle in the cervico-costoclavicular-axillary area, and evaluate the histological changes of nerve after the stretch test. Material and Methods: During the cadaveric study on 7 specimens 7-20 h after death, strain deformation of plexus brachialis as well as compression deformation caused by the surrounding structures of the neurovascular bundle were investigated in the arm abduction position of 0°, 90°, 12°, 150°, and 180°. One nerve sample was studied histologically after 15% stretch on the bench. Results: The relative strain deformation of 3%-23% was documented during 0° to 180° abduction tests. The strain deformation from 0° to 90° was significant (P<0.001). The mean pressure change in the bundle was 13.6 mm Hg at 90°, 53.7 mm Hg at 120°, 73.4 mm Hg at 150°, and 89.0 mm Hg at 180° arm abduction. An increase in pressure was significant in the intervals: 0°-90° (P<0.001), 91°-120° (P<0.001), 121°-150° (P<0.001) and 151°-180° (P<0.05). Conclusions: Nerve traction and tissue compression arising during the arm abduction above 90° were found to be sufficient to induce lesions in neural bundles of the plexus brachialis.Item The Role of the p16 and p53 Tumor Suppressor Proteins and Viral HPV16 E6 and E7 Oncoproteins in the Assessment of Survival in Patients with Head and Neck Cancers Associated with Human Papillomavirus Infections(2023-05-11) Lifsics, Andrejs; Cistjakovs, Maksims; Sokolovska, Liba; Deksnis, Renars; Murovska, Modra; Groma, Valerija; Department of Otorhinolaryngology; Institute of Microbiology and Virology; Institute of Anatomy and AnthropologyThe role of HPV in the survival prognosis of patients with head and neck squamous cell carcinoma, especially patients with laryngeal squamous cell carcinoma (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC), is still somewhat ambiguous. The present study aimed to explore the significance of tumor suppressor proteins and HPV16 E6 and E7 oncoproteins in the assessment of survival in patients with oropharyngeal squamous cell carcinoma (OPSCC), LSCC, and HPSCC associated with high-risk (HR-) and low-risk (LR-) HPV infections. By utilizing molecular and immunohistochemical investigations of HNSCC samples and patient data, univariate and multivariate survival analyses were conducted. The presence of HPV DNA (LR- and HR-HPV) was associated with a better 5-year OS and DSS for OPSCC and LSCC. The IHC overexpression of HPV16 E6 protein and p16 protein was associated with better survival in the univariate (for OPSCC) and multivariate (OPSCC and HPSCC) survival analyses. The overexpression of p53 was associated with better survival in OPSCC. HPV infection plays a significant role in the tumorigenesis of HNSCC, and the immunohistochemical assessment of HPV16 E6 protein expression should be interpreted as a useful prognostic marker for OPSCC and HPSCC.Item Structural and ultrastructural alterations in human olfactory pathways and possible associations with herpesvirus 6 infection(2017-01) Skuja, Sandra; Zieda, Anete; Ravina, Kristine; Chapenko, Svetlana; Roga, Silvija; Teteris, Ojars; Groma, Valerija; Murovska, Modra; Institute of Anatomy and Anthropology; Institute of Microbiology and VirologyStructural and ultrastructural alterations in human olfactory pathways and putative associations with human herpesvirus 6 (HHV-6) infection were studied. The olfactory bulb/tract samples from 20 subjects with an unspecified encephalopathy determined by pathomorphological examination of the brain autopsy, 17 healthy age-matched and 16 younger controls were used. HHV-6 DNA was detected in 60, 29, and 19% of cases in these groups, respectively. In the whole encephalopathy group, significantly more HHV-6 positive neurons and oligodendrocytes were found in the gray matter, whereas, significantly more HHV-6 positive astrocytes, oligodendrocytes, microglia/macrophages and endothelial cells were found in the white matter. Additionally, significantly more HHV-6 positive astrocytes and, in particular, oligodendrocytes were found in the white matter when compared to the gray matter. Furthermore, when only HHV-6 PCR+ encephalopathy cases were studied, we observed similar but stronger associations between HHV-6 positive oligodendrocytes and CD68 positive cells in the white matter. Cellular alterations were additionally evidenced by anti-S100 immunostaining, demonstrating a significantly higher number of S100 positive cells in the gray matter of the whole encephalopathy group when compared to the young controls, and in the white matter when compared to both control groups. In spite the decreased S100 expression in the PCR+ encephalopathy group when compared to PCR- cases and controls, groups demonstrated significantly higher number of S100 positive cells in the white compared to the gray matter. Ultrastructural changes confirming the damage of myelin included irregularity of membranes and ballooning of paranodal loops. This study shows that among the cellular targets of the nervous system, HHV-6 most severely affects oligodendrocytes and the myelin made by them.Item Synovitis in osteoarthritic patients : Morphological and virological evidence of its contribution to development of the disease(2019-08-01) Tarasovs, Mihails; Skuja, Sandra; Semenistaja, Sofija; Murovska, Modra; Groma, Valerija; Institute of Anatomy and Anthropology; Department of Internal Diseases; Institute of Microbiology and VirologyThe role of inflammation in the development of osteoarthritic joint degeneration is not completely understood. Recent data suggest that processes that cause and orchestrate inflamed synovial lesions may be implicated in the development of the disease. The morphological changes of the synovium in patients with osteoarthritis (OA), as well as the level of synovial inflammation cautiously graded, in association to the presence of human parvovirus B19 (B19V) infection markers, were evaluated. Qualitative and quantitative detection of B19V genomic sequence was performed in OA and rheumatoid arthritis (RA) groups. The expression of CD68, S100 (Ca2+ binding proteins soluble in 100% ammonium sulfate) and B19 VP1/VP2 capsid proteins found in the synovium were investigated by single and double immunolabeling, whereas fine features of synoviocytes - by electron microscopy. One-third of OA and RA patients demonstrated synovial expression of B19V antigen, which was confirmed in both types of synoviocytes. The overall expression of B19V in OA patients was weaker than that found in RA subjects. Positive correlation between B19V-positive vascular endothelial cells, sublining infiltrating lymphocytes, macrophages, and B19V-positive synoviocytes was established. No correlation between synovitis score indices as well as the expression of S100 and expression of B19V was found. The results suggest that the synovial membrane maintains local joint homeostasis, and that virus mediated synovitis is implicated in the development of OA.Item Ultrastructural Characterization of the Frontal Lobe in the Case of Human Herpes Virus-6 Infection(2020-06-24) Skuja, Sandra; Groma, Valerija; Murovska, ModraThe vast majority of the world’s population is exposed to beta-herpesviruses during early childhood. After the primary infection, human herpesvirus-6 (HHV-6) can establish a lifelong persistence. The role of HHV-6 in the development of neurodegenerative disorders is not completely clarified. Postmortem samples of brain tissue obtained from 24 elderly subjects with unspecified encephalopathy were used in the study. Nested (nPCR) and real-time polymerase chain reaction (RT PCR) were used for the qualitative and quantitative detection of viral genomic sequences in isolated DNA from frontal lobe samples. For ultrastructural examination, transmission electron microscopy (TEM), nPCR, and immunohistochemically confirmed HHV-6-positive tissue samples were used. Immunogold (IG) labeling using anti-HHV-6 (20) mouse monoclonal antibodies, raised against viral lysate (Santa Cruz Biotechnology, dilution 1:30), was performed. HHV-6 DNA was detected in 38% (9/24) of the frontal lobe tissue samples. The HHV-6 load in the nPCR-positive samples ranged from 10 to 3878.5 (copies/106 cells). A TEM examination of the frontal cortex revealed lipofuscin containing neurons, glial cells, unmyelinated and small myelinated axons, and symmetric synapses. Subcortical brain regions revealed glial cells interspersed by myelinated axons. The expression of viral proteins was found in the nuclei of neurons, demonstrating disarranged chromatin. HHV-6 positivity was detected between the adjacent cisternae of the rough endoplasmic reticulum of neurons displaying IG labeling. Furthermore, products of IG labeling were found in nuclei and cytoplasm of oligodendrocytes. The cytoplasm of astrocytes was IG labeled as well. IG labeling was used to determine the presence and intracellular localization of HHV-6 proteins in the human brain. HHV-6 possibly contributes to the demyelination process via entry into and affection of oligodendrocytes. Finally, neural susceptibility to HHV-6 may be linked to an invalid cellular immune response, followed by the development of a persistent viral infection.Item Upregulated tissue expression of T helper (Th) 17 pathogenic interleukin (IL)-23 and IL-1β in Hashimoto’s thyroiditis but not in graves’ disease(2019) Zake, Tatjana; Skuja, Sandra; Kalere, Ieva; Konrade, Ilze; Groma, Valerija; Department of Internal Diseases; Institute of Anatomy and AnthropologyT helper (Th) 17 cells and interleukin (IL)-17 play a significant role in the pathogenesis of autoimmune thyroid disease (AITD). However, it has recently become clear that Th17 cells are more heterogeneous and exhibit two different phenotypes, whereas IL-23 and IL-1β are crucial for the generation of pathogenic Th17 lymphocytes. We aimed to investigate the association between IL-17 and Th17-promoting cytokines in AITD by studying the immunoexpression patterns of IL-17, IL-23, and IL-1β in thyroid tissue. Following thyroidectomy, 29 patients with AITD (21 cases of Hashimoto’s thyroiditis (HT) and 8 cases of Graves’ disease (GD)) and 18 patients with colloid goiter, as controls, were enrolled in this study, and immunohistochemistry was performed. The expression level of IL-17 in thyrocytes was significantly higher in HT and GD patients than in colloid goiter patients. Immunopositivity for both IL-23 and IL-1β was significantly increased in HT patients compared to GD and colloid goiter patients. However, no difference was found between IL-23 or IL-1β expression in patients with GD and colloid goiter. A positive correlation between IL-17 and IL-23 as well as IL-17 and IL-1β expression was observed in HT patients (r = 0.574, p = 0.007 and r = 0.461, p = 0.036, respectively). In the GD group, IL-17 was positively correlated with IL-1β (r = 0.817, p = 0.013) but not with IL-23 expression. We found increased IL-23 and IL-1β expression in the HT group but not in the GD group. Furthermore, both interleukins were correlated with IL-17 immunopositivity in thyroid tissue, suggesting that pathogenic Th17-promoting cytokines may play a role in HT pathogenesis.