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Copyright of Acta Facultatis Medicae Naissensis is the property of Nis University, Faculty of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Selenium (Se) is an essential trace element that is involved in numerous biological processes in the form of a selenoprotein such as iodothyronine deiodinase (DIO). Se deficiency may prevent the conversion of T4 to T3 through reducing DIO expression and thereby affecting thyroid hormone status. However, this has not been well documented in humans. In this study, to clarify the association between Se and thyroid hormone status, we investigated the thyroid hormone levels in patients with severe Se deficiency (< 2 μg/dl). Severe Se deficiency was associated with increases in free T4 levels, but not with decreases and increases in free T3 and thyroid stimulating hormone (TSH) levels, respectively. Increases in free T4 levels during Se deficiency were reduced with Se supplementation; however, neither free T3 nor TSH levels were affected. Taken together, these findings indicate that free T4 may be a useful biomarker for Se status when serum Se levels are severely low. [ABSTRACT FROM AUTHOR]

In the fruit fly optic lobe, T4 and T5 cells represent the first direction-selective neurons, with T4 cells responding selectively to moving brightness increments (ON) and T5 cells to brightness decrements (OFF). Both T4 and T5 cells comprise four subtypes with directional tuning to one of the four cardinal directions. We had previously found that upward-sensitive T4 cells implement both preferred direction enhancement and null direction suppression (Haag et al., 2016). Here, we asked whether this mechanism generalizes to OFF-selective T5 cells and to all four subtypes of both cell classes. We found that all four subtypes of both T4 and T5 cells implement both mechanisms, that is preferred direction enhancement and null direction inhibition, on opposing sides of their receptive fields. This gives rise to the high degree of direction selectivity observed in both T4 and T5 cells within each subpopulation. [ABSTRACT FROM AUTHOR]

The perception of visual motion is critical for animal navigation, and flies are a prominent model system for exploring this neural computation. In Drosophila, the T4 cells of the medulla are directionally selective and necessary for ON motion behavioral responses. To examine the emergence of directional selectivity, we developed genetic driver lines for the neuron types with the most synapses onto T4 cells. Using calcium imaging, we found that these neuron types are not directionally selective and that selectivity arises in the T4 dendrites. By silencing each input neuron type, we identified which neurons are necessary for T4 directional selectivity and ON motion behavioral responses. We then determined the sign of the connections between these neurons and T4 cells using neuronal photoactivation. Our results indicate a computational architecture for motion detection that is a hybrid of classic theoretical models. [ABSTRACT FROM AUTHOR]

Virtually all studies of phage infections investigate bacteria growing exponentially in rich media. In nature, however, phages largely encounter non-growing cells. Bacteria entering stationary phase often activate well-studied stress defense mechanisms that drastically alter the cell, facilitating its long-term survival. An understanding of phagehost interactions in such conditions is of major importance from both an ecological and therapeutic standpoint. Here, we show that bacteriophage T4 can efficiently bind to, infect and kill E. coli in stationary phase, both in the presence and absence of a functional stationary-phase sigma factor, and explore the response of T4-infected stationary phase cells to the addition of fresh nutrients 5 or 24 h after that infection. An unexpected new mode of response has been identified. "Hibernation" mode is a persistent but reversible dormant state in which the infected cells make at least some phage enzymes, but halt phage development until appropriate nutrients become available before producing phage particles. Our evidence indicates that the block in hibernation mode occurs after the middle-mode stage of phage development; host DNA breakdown and the incorporation of the released nucleotides into phage DNA indicate that the enzymes of the nucleotide synthesizing complex, under middle-mode control, have been made and assembled into a functional state. Once fresh glucose and amino acids become available, the standard lytic infection process rapidly resumes and concentrations of up to 1011 progeny phage (an average of about 40 phage per initially present cell) are produced. All evidence is consistent with the hibernation-mode control point lying between middle mode and late mode T4 gene expression. We have also observed a "scavenger" response, where the infecting phage takes advantage of whatever few nutrients are available to produce small quantities of progeny within 2 to 5 h after infection. The scavenger response seems able to produce no more than an average of one phage per originally available cell, and few if any further progeny are produced by cells in this mode even if fresh nutrients are made available later. [ABSTRACT FROM AUTHOR]

Objectives Low normal thyroid function may promote the development of atherosclerotic cardiovascular disease by thus far poorly defined mechanisms. We tested the impact of thyroid function on HDL antioxidative capacity, a metric of its antiatherogenic functionality, in euthyroid subjects with varying degrees of glucose tolerance. Design and Subjects Seventy subjects with Type 2 diabetes mellitus (T2 DM), 37 subjects with impaired fasting glucose ( IFG) and 31 subjects with normal fasting glucose ( NFG) (revised NCEP- ATPIII criteria) participated in a cross-sectional study. Measurements HDL antioxidative capacity (standardized for HDL cholesterol) was measured as the percentage inhibition of low-density lipoprotein oxidation in vitro. Results TSH, free T4 and HDL antioxidative capacity were not different among NFG, IFG and T2 DM subjects ( P > 0·25 for each). HDL antioxidative capacity was correlated positively with free T4 ( r = 0·320, P = 0·007), and negatively with plasma glucose ( r = −0·394, P < 0·001) in T2 DM only. Taking account of age and sex, the relationship of HDL antioxidative functionality with free T4 was modified by glucose tolerance status ( P = 0·040 and P = 0·008 for interactions of IFG and T2 DM with free T4 respectively). Prevailing plasma glucose also interacted positively with free T4 on HDL antioxidative capacity ( P = 0·054). Conclusions In the context of chronic hyperglycaemia, low free T4 within the euthyroid range confers diminished HDL antioxidative capacity, a pathophysiologically relevant metric of HDL functionality. [ABSTRACT FROM AUTHOR]

During persistent viral infections, chronic immune activation, negative immune regulator expression, an elevated interferon signature, and lymphoid tissue destruction correlate with disease progression. We demonstrated that blockade of type I interferon (IFN-I) signaling using an IFN-I receptor neutralizing antibody reduced immune system activation, decreased expression of negative immune regulatory molecules, and restored lymphoid architecture in mice persistently infected with lymphocytic choriomeningitis virus. IFN-I blockade before and after establishment of persistent virus infection resulted in enhanced virus clearance and was CD4 T cell-dependent. Hence, we demonstrate a direct causal link between IFN-I signaling, immune activation, negative immune regulator expression, lymphoid tissue disorganization, and virus persistence. Our results suggest that therapies targeting IFN-I may help control persistent virus infections. [ABSTRACT FROM AUTHOR]

Type I interferons (IFN-I) are critical for antiviral immunity; however, chronic IFN-I signaling is associated with hyperimmune activation and disease progression in persistent infections. We demonstrated in mice that blockade of IFN-I signaling diminished chronic immune activation and immune suppression, restored lymphoid tissue architecture, and increased immune parameters associated with control of virus replication, ultimately facilitating clearance of the persistent infection. The accelerated control of persistent infection induced by blocking IFN-I signaling required CD4 T cells and was associated with enhanced IFN-y production. Thus, we demonstrated that interfering with chronic IFN-I signaling during persistent infection redirects the immune environment to enable control of infection. [ABSTRACT FROM AUTHOR]

The expression of the CD11b antigen and the presence of the S-100 (and, specifically, its β subunit) protein within the T4- subpopulation of normal human peripheral blood lymphocytes were investigated by panning techniques, itnmunofluorescence analysis and immunoelectronmicroscopy. Both antigens are known to be absent in the T4+ lymphocytes. However, CD11b+ T lymphocytes represented about 30% of the T4- population; a part of them (over 1/3) belonged to and completely filled up the T4- T8- subpopulation, whereas the remaining part (almost 2/3) shared the T8 positivity. Interestingly, S-100+ T lymphocytes, which always were CD11b+ too, represented about one half of the CD11b+ T cells, but were excluded from the T4- T8- CD11b+ subpopulation, whereas they represented up to 80% of theT4- T8- CD11 b+ subset. Such findings demonstrate that the S-100+ T lymphocytes are exclusively restricted to a discrete T cell compartment which shows the T8+ CD11b+ immunophenotype. Since such T8+ CD11b+ cells had been shown to possess suppressive capabilities, we herein propose that S-100+ lymphocytes might to some extent modulate the immune responses. However, the exact functional significance of the S-100 protein stilt remains unknown. [ABSTRACT FROM AUTHOR]

The effect of iron (Fe3+) and normal human liver ferritin on the proliferative response of normal human lymphocytes to tetanus toxoid was examined. This proliferative response involved memory T4+ lymphocytes as shown by a selective depletion study. Limit dilution analysis revealed that iron, present as ferric citrate, affected the initiation of clone development, and that concentrations of ferric citrate from 30 μM to 1 mM were able to reduce significantly the cloning efficiency of precursor T cells (up to 90% reduction). The reduced cloning frequency was not due to immunological suppression. Clone size was also reduced when iron was present during culture. In contrast, the presence of normal human liver ferritin during culture (concentration range: 300μg/l-10,000 /μg/1) had no effect on lymphocyte proliferation. The data indicate that low molecular weight iron (as ferric citrate) in concentrations similar to those which have been reported in the serum of patients with iron overload diseases, can interfere with antigen-specific lymphocyte responses and this may have implications for the development of infections and neoplasia in diseases of iron-overload. [ABSTRACT FROM AUTHOR]

We studied the possible in vivo influence of cimetidine on peripheral blood lymphocyte (PBL) subpopulations defined with monoclonal antibodies (MoAb) in eight haematologically normal patients with uncomplicated duedenal ulcers before cimetidine treatment, 1 week after the start, and finally 1 week following cessation of therapy. Alter cimetidine had been given for 3-5 weeks there was a significant decrease, compared with pretreatment numbers, in the proportion of T3+ cells (64.6±8.1 (mean ± s.d.) v 51.0 ± 7.8%) and in T4+ cells (47. 3 ± 4 .3 v 30. 8 ± 4.7%). The number of T8+ cells was not affected (20. 3 ± 4 .3 v 20.1 ±6.7%). These changes resulted in a significant reduction in the T4/T8 ratio (2.46 ± 0.8 v 1.67 ± 0.6). The total numbers of lymphocytes and monocytes as well as the percentage of B1+ lymphocytes did not change significantly. The observed decrease in T4/T8 ratio after cimetidine treatment is explained by a reduction in the number of T4+ cells and the appearance of a new subpopulation of T3-, T4-, T8-, B1- lymphocytes. The underlying mechanism, however, is not clear. Cimetidine does not seem to have a direct receptor-modulating effect, since in vitro exposure of normal lymphocytes to the drug did not change the proportions of the T cell subsets. [ABSTRACT FROM AUTHOR]

Twenty-two patients with active pulmonary sarcoidosis had the subpopulations of the lymphocytes in the bronchoalveolar lavage (BAL) fluid measured. All 12 with hypergammaglobulinaemia had a ratio less than 2.0 (χ²=5.18, P<0.025). When an increased number of T4 lymphocytes was present in the BAL fluid, there was a significant decrease in the absolute number of T4 lymphocytes in the peripheral blood (χ²=6.84, P<0.01). The number of T4 lymphocytes in the BAL fluid correlated with the subsequent response to daily steroid therapy for 2 months, as assessed by improvement in vital capacity (r=0.89, P<0.01). [ABSTRACT FROM AUTHOR]

Monoclonal antibody BE2 recognizes an antigen found on malignant T4+ lymphocytes from cutaneous T-cell lymphoma patients (CTCL). Normal peripheral blood lymphocytes do not express detectable levels of BE2 antigen. Forty-eight percent of patients with the acquired immunodeficiency syndrome (AIDS) had lymphocyte populations that were reactive with monoclonal antibody BE2. Peripheral blood lymphocytes from healthy homosexuals, patients with classical Kaposi's sarcoma or viral syndromes and healthy normal controls were BE2-. Double-labeling studies demonstrated that BE2+ cells were T lymphocytes This observation demonstrates that some AIDS patients as well as CTCL patients have circulating cells that express a common lymphocyte abnormality. [ABSTRACT FROM AUTHOR]

Infection with human immunodeficiency virus (HIV) causes an extensive array of immunologic abnormalities which ultimately lead to severe immunosuppression, opportunistic disease, and death. Many of the immunologic defects can be attributable to the quantitative and qualitative deficiencies of T4 lymphocytes caused by HIV. Other abnormalities may reflect chronic HIV exposure to or infection of other immunologic cells including B cells and monocyte/macrophages. A summary of the potential mechanisms of pathogenesis of HIV infection is shown in fig. 2. One of the most puzzling aspects of infection with HIV is the length and variability of time between initial infection and disease. It appears that activation of latent or chronic, smoldering infection into active disease may be the result of a variety of factors, including heterologous viruses and cytokines, whose common denominator is the ability to induce the production of DNA-binding proteins that interact with the HIV-LTR and induce transcription of virus. [ABSTRACT FROM AUTHOR]

The role of minimally invasive surgery (MIS) to treat clinically T4 (cT4) colorectal cancer (CRC) remains uncertain and deserves further investigation. A retrospective cohort study was conducted between September 2006 and March 2019 recruiting patients diagnosed as cT4 CRC and undergoing MIS at a university hospital and its branch. Patients' demography, clinicopathology, surgical and oncological outcomes, and radicality were analyzed. A total of 128 patients were recruited with an average follow-up period of 33.8 months. The median time to soft diet was 6 days, and the median postoperative hospitalization periods was 11 days. The conversion and complication (Clavien–Dindo classification ≥ II) rates were 7.8% and 27.3%, respectively. The 30-day mortality was 0.78%. R0 resection rate was 92.2% for cT4M0 and 88.6% for pT4M0 patients. For cT4 CRC patients, the disease-free survival and 3-year overall survival were 86.1% and 86.8% for stage II, 54.1% and 57.9% for stage III, and 10.8% and 17.8% for stage IV. With acceptable conversion, complication and mortality rate, MIS may achieve satisfactory R0 resection rate and thus lead to good oncological outcomes for selected patients with cT4 CRC. [ABSTRACT FROM AUTHOR]

The induction of HIV-1-specific antibodies that can neutralize a broad number of isolates is a major goal of HIV-1 vaccination strategies. However, to date no candidate HIV-1 vaccine has successfully elicited broadly neutralizing antibodies of sufficient quality and breadth for protection. In this review, we focus on the role of follicular helper CD4 T-cells (Tfh) in the development of such cross-reactive protective antibodies. We discuss germinal center (GC) formation and the dynamics of Tfh and GC B cells during HIV-1/SIV infection and vaccination. Finally, we consider future directions for the study of Tfh and offer perspective on factors that could be modulated to enhance Tfh function in the context of prophylactic vaccination. [ABSTRACT FROM AUTHOR]

The article discusses reports within the issue about the role of type 1 interferon (IFN) suppression in viral infections. Researchers J. R. Teijaro and team and E. B. Wilson and colleagues focused on the effect of lymphocytic choriomeningitis virus infection (LCMV) in mouse models on IFN production. Both teams found that inhibition of IFN receptors promoted virus replication and decreased immunosuppressive molecule expression, but also increased CD4* T cell activity against the virus and lymphoid organization. It is suggested that interferon displays both antiviral and immunoregulatory functions during infection and that these activities could be targeted for therapeutic applications.

Focuses on the implication of abnormal sweat electrolyte secretion in the diagnosis of the immunodeficiency virus infection of a child in Great Britain. Histological and epidemiological background of the disease; Verification of hyperglobulinemia neutropenia and T4 lymphocytes composition; Details of the diagnosis.