Salehlang7655

The co-administration of kisspeptin or RF9 with paroxetine prevented the paroxetine-induced negative effects on seminal vesicle fluid components. These results suggest that reduction in sperm fertilising ability caused by changes in seminal vesicle fluid can be seen in long-term antidepressant use. RF-9 and kisspeptin might have positive effects on long-term antidepressant use-induced infertility. © 2020 Blackwell Verlag GmbH.Neutropenia (NP), that is, an absolute blood neutrophil count (ANC) 370 000 individuals, we identified and followed neutropenic subjects for the next 4 years for novel ICD-10 based diagnoses of viral infections and hematological malignancies (ie, previously identified major outcomes in NP individuals) in Danish nationwide health registers. Risk estimates were assessed for children/adolescents (1-18 years) and adults (19-90 years) in relation to NP severity, and for isolated NP, bi- or pancytopenias. We found that NP was observed in 4.9% of children and in 1.9% of adults. The lower the ANC, the likelier was a diagnosis of viral infections or hematological malignancies established during the ensuing 4 years. Among neutropenic children, unspecified viral infections predominated, followed by mononucleosis (with other cytopenias in only 7% and 25% of the cases, respectively). All NP children with acute leukemia presented with bi- or pancytopenia from start of follow-up. In NP adults, hepatitis, followed by HIV, were the most common infections, and acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDSs) the predominating hematological malignancies. Adult NP patients, subsequently diagnosed with hepatitis, HIV or AML, MDS, were bi- or pancytopenic in 42%, 47%, 90% and 91% of cases, respectively. Thus, presence of NP in even one CBC may be the first sign of a latent viral or hematological disorder requiring careful follow-up. © 2020 Wiley Periodicals, Inc.The cellular origin of CD4- CD8- (double negative, DNT) TCR-α/β+ T cells remains unknown. Available evidence indicates that they may derive from CD8+ T cells, but most published data have been obtained using cells that bear an invariant transgenic T cell receptor that recognizes an Ag that is not present in normal mice. click here Here, we have used complementary fate mapping and adoptive transfer experiments to identify the cellular lineage of origin of DNT cells in wild-type mice with a polyclonal T cell repertoire. We show that TCR-α/β+ DNT cells can be traced back to CD8+ and CD4+ CD8+ double positive cells in the thymus. We also demonstrate that polyclonal DNT cells generated in secondary lymphoid organs proliferate upon adoptive transfer and can regain CD8 expression in lymphopenic environment. These results demonstrate the cellular origin of DNT cells and provide a conceptual framework to understand their presence in pathological circumstances. ©2020 Society for Leukocyte Biology.CD137 is a potent costimulatory receptor. Several agonistic anti-CD137 antibodies are currently in clinical trials for tumor immunotherapy. Soluble forms of CD137 (sCD137) are generated by differential splicing and antagonize the activities of membrane-bound CD137 (mCD137) and of therapeutic CD137 agonists. sCD137 is found in sera of patients suffering from autoimmune diseases where it is a natural regulator of immune responses, and which has therapeutic potential for immune-mediated diseases. This review summarizes the current knowledge on sCD137, highlights its potential role in immunotherapy against cancer and in autoimmune diseases, and presents important issues to be addressed by future research. ©2020 Society for Leukocyte Biology.CCR4 is the sole receptor for the chemokines CCL22 and CCL17. Clinical studies of asthmatic airways have shown levels of both ligands and CCR4+ Th2 cells to be elevated, suggestive of a role in disease. Consequently, CCR4 has aroused much interest as a potential therapeutic target and an understanding of how its cell surface expression is regulated is highly desirable. To this end, receptor expression, receptor endocytosis, and chemotaxis were assessed using transfectants expressing CCR4, CCR4+ human T cell lines, and human Th2 cells polarized in vitro. CCL17 and CCL22 drove rapid endocytosis of CCR4 in a dose-dependent manner. Replenishment at the cell surface was slow and sensitive to cycloheximide, suggestive of de novo synthesis of CCR4. Constitutive CCR4 endocytosis was also observed, with the internalized CCR4 found to be significantly degraded over a 6-h incubation. link2 Truncation of the CCR4 C-terminus by 40 amino acids had no effect on cell surface expression, but resulted in significant impairment of ligand-induced endocytosis. Consequently, migration to both CCL17 and CCL22 was significantly enhanced. In contrast, truncation of CCR4 did not impair constitutive endocytosis or degradation, suggesting the use of alternative receptor motifs in these processes. We conclude that CCR4 cell surface levels are tightly regulated, with a degradative fate for endocytosed receptor. We postulate that this strict control is desirable, given that Th2 cells recruited by CCR4 can induce the further expression of CCR4 ligands in a positive feedback loop, thereby enhancing allergic inflammation. © 2020 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals, Inc. on behalf of Society for Leukocyte Biology.BACKGROUND The aim of this study was to compare the macular and peripapillary vessel densities in eyes of young Chinese adults with different degrees of myopia and to evaluate the association of macular and peripapillary vessel densities with axial length and retinal nerve fibre layer thickness. METHODS A total of 128 eyes (mild myopia, 42; moderate myopia, 45; severe myopia, 41) underwent optical coherence tomography angiography imaging. Parameters assessed were vessel densities in the superficial capillary plexus and deep capillary plexus of the macular area, peripapillary vessel density, retinal nerve fibre layer thickness, foveal thickness and foveal avascular zone area (mm2 ). RESULTS Vessel densities in the macular and peripapillary areas as well as peripapillary retinal nerve fibre layer thickness decreased significantly when comparing high myopia to mild myopia. Axial length was significantly associated with vessel density in the macular area (superficial capillary plexus r = -0.249, p = 0.008; deep capillary plexus r = -0.398, p  less then  0.001), peripapillary area (r = -0.204, p = 0.028), foveal avascular zone area (r = -0.309, p  less then  0.001), and foveal thickness (r = 0.354, p  less then  0.001). Negative correlations were found between axial length and peripapillary vessel density as well as retinal nerve fibre layer thickness at the nasal superior, nasal inferior and inferior nasal quadrants. CONCLUSION Varying degrees of myopia affected macular and peripapillary vessel densities as well as retinal nerve fibre layer thickness in young healthy adults. The high myopic group had the lowest vessel density in the superficial capillary plexus, deep capillary plexus of the macular area and the peripapillary area. With increased axial length, macular and peripapillary vessel densities, retinal nerve fibre layer thickness and foveal avascular zone area reduced while foveal thickness increased. © 2020 Optometry Australia.Male subfertility has been associated with bacterial infections and chronic inflammation. In this context, several studies investigated cytokine levels in seminal plasma, whereas interleukin-6 (IL-6) appears to be crucial. However, little is known about its receptor, the IL-6R expression on human spermatozoa. Thus, the aim of the present study was to screen spermatozoa for IL-6R expression and to identify its localisation. Semen samples of 137 patients (median age 37.69, SD ± 7.82) with subfertility were analysed. Sperm analysis including determination of IL-6 was performed following the World Health Organization criteria. Also, flow cytometry was performed for sperm IL-6R expression. IL-6R+ cells were used for immunofluorescence staining to identify receptor localisation. The results showed positive staining for IL-6R in the midpiece of spermatozoa. Furthermore, a significant correlation between sperm IL-6R expression, seminal plasma IL-6 and total sperm count could be demonstrated, whereas a negative correlation was observed in sperm IL-6R expression and motility. However, no statistical significance could be observed between IL-6R expression, vitality and morphology. Moreover, incubation of spermatozoa with IL-6 led to a slight but significant decrease in motility after 24 hr. These data suggest that IL-6R expression may play a role in impaired sperm function during inflammation. © 2020 The Authors. Andrologia published by Blackwell Verlag GmbH.Urelumab, a fully human, non-ligand binding, CD137 agonist IgG4 monoclonal antibody, enhances T-cell and natural killer-cell antitumor activity in preclinical models, and may enhance cytotoxic activity of rituximab. Here we report results in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and other B-cell lymphomas, in phase 1 studies evaluating urelumab alone (NCT01471210) or combined with rituximab (NCT01775631). Sixty patients received urelumab (0.3 mg/kg IV Q3W, 8 mg IV Q3W, or 8 mg IV Q6W); 46 received urelumab (0.1 mg/kg, 0.3 mg/kg, or 8 mg IV Q3W) plus rituximab 375 mg/m2 IV QW. The maximum tolerated dose (MTD) of urelumab was determined to be 0.1 mg/kg or 8 mg Q3W after a single event of potential drug-induced liver injury occurred with urelumab 0.3 mg/kg. Treatment-related AEs were reported in 52% (urelumab grade 3/4, 15%) and 72% (urelumab + rituximab grade 3/4, 28%); three led to discontinuation (grade 3 increased AST, grade 4 acute hepatitis [urelumab]; one death from sepsis syndrome [urelumab plus rituximab]). Objective response rates/disease control rates were 6%/19% (DLBCL, n = 31), 12%/35% (FL, n = 17), and 17%/42% (other B-cell lymphomas, n = 12) with urelumab and 10%/24% (DLBCL, n = 29) and 35%/71% (FL, n = 17) with urelumab plus rituximab. Durable remissions in heavily pretreated patients were achieved; however, many were observed at doses exceeding the MTD. link3 These data show that urelumab alone or in combination with rituximab demonstrated manageable safety in B-cell lymphoma, but the combination did not enhance clinical activity relative to rituximab alone or other current standard of care. © 2020 Wiley Periodicals, Inc.PURPOSE Imaging the carotid arteries at 7T ideally requires a flexible multichannel array that allows B1-shimming and conforms to different neck sizes. The major challenge is to minimize coupling between closely spaced coils and to make the coupling relatively insensitive to loading conditions. METHODS We have designed a five-channel flexible transceive array composed of shielded-coaxial-cable coils placed on the anterior part of the neck and conforming to the anatomy. In vivo imaging of the carotid arteries in three subjects has been performed. RESULTS The measured noise correlation matrices show the decoupling level between the individual elements to be -12.5 dB and better. Anatomical localizer imaging of the carotids shows both carotids in every subject well visualized after B1-shimming. In vivo black-blood, carotid images were acquired with very high in-plane spatial resolution (0.25 × 0.25 mm2 ) with clear depiction of the vessel walls. CONCLUSIONS The flexibility of the proposed coil has been demonstrated by imaging subjects with different neck circumferences.