Publications by authors named "Tatiana Kochetkov"
Article Synopsis
- * This deficiency results in the impaired translation of important proteins like JAK2, affecting cellular responses to specific cytokines such as IL-23 and IL-12, particularly in T lymphocytes and phagocytes.
- * The impaired response to IL-23 reduces the production of IFN-γ by certain immune cells during mycobacterial infections, highlighting a crucial link between MCTS1 deficiency and mycobacterial disease susceptibility.
Article Synopsis
- Patients with autosomal recessive (AR) IL-12p40 or IL-12Rβ1 deficiencies are prone to mycobacterial diseases (MSMD) due to low IFN-γ production, and may also experience chronic mucocutaneous candidiasis (CMC) from reduced IL-17A/F production.
- The study identifies six patients with AR IL-23R deficiency, all showing MSMD symptoms, but CMC only in two, linked to specific genetic variants affecting IL-23's function.
- IL-23 is essential for stimulating IFN-γ immunity in certain immune cells and plays a more limited role in IL-17A production, shedding light on why some patients have a higher incidence of
Article Synopsis
- Researchers have identified a connection between haploinsufficiency of the OTULIN gene and severe responses to staphylococcal infections in patients, leading to life-threatening necrosis.
- This condition is similar to the symptoms seen in Cri-du-Chat syndrome, which involves a deletion on chromosome 5p.
- The impairment from OTULIN causes an accumulation of linear ubiquitin in skin cells, leading to increased vulnerability to the staphylococcal toxin α-toxin, despite no changes in blood immune cells.
Autosomal recessive IRF7 and IRF9 deficiencies impair type I and III IFN immunity and underlie severe influenza pneumonitis. We report three unrelated children with influenza A virus (IAV) infection manifesting as acute respiratory distress syndrome (IAV-ARDS), heterozygous for rare variants (P554S in two patients and P680L in the third) causing autosomal dominant (AD) TLR3 deficiency. AD TLR3 deficiency can underlie herpes simplex virus-1 (HSV-1) encephalitis (HSE) by impairing cortical neuron-intrinsic type I IFN immunity to HSV-1.
View Article and Find Full Text PDFApproximately 90% of patients with isolated agammaglobulinemia and failure of B cell development have mutations in genes required for signaling through the pre–B cell and B cell receptors. The nature of the gene defect in the majority of remaining patients is unknown. We recently identified 4 patients with agammaglobulinemia and markedly decreased numbers of peripheral B cells.
View Article and Find Full Text PDFChronic mucocutaneous candidiasis disease (CMCD) may be caused by autosomal dominant (AD) IL-17F deficiency or autosomal recessive (AR) IL-17RA deficiency. Here, using whole-exome sequencing, we identified heterozygous germline mutations in STAT1 in 47 patients from 20 kindreds with AD CMCD. Previously described heterozygous STAT1 mutant alleles are loss-of-function and cause AD predisposition to mycobacterial disease caused by impaired STAT1-dependent cellular responses to IFN-γ.
View Article and Find Full Text PDFUnlabelled: PURPOSE/EXPERIMENTAL DESIGN: Treatment of cerebral tumors and peritumoral brain edema remains a clinical challenge and is associated with high morbidity and mortality. Dexamethasone is an effective drug for treating brain edema, but it is associated with well-documented side effects. Corticorelin acetate (Xerecept) or human corticotrophin-releasing factor (hCRF) is a comparatively new drug and has been evaluated in two orthotopic glioma models (U87 and C6), by a direct comparison with dexamethasone and temozolomide.
View Article and Find Full Text PDFPurpose: To determine whether treatment response to the Aurora B kinase inhibitor, AZD1152, could be monitored early in the course of therapy by noninvasive [(18)F]-labeled fluoro-2-deoxyglucose, [(18)F]FDG, and/or 3'-deoxy-3'-[(18)F]fluorothymidine, [(18)F]FLT, PET imaging.
Experimental Design: AZD1152-treated and control HCT116 and SW620 xenograft-bearing animals were monitored for tumor size and by [(18)F]FDG, and [(18)F]FLT PET imaging. Additional studies assessed the endogenous and exogenous contributions of thymidine synthesis in the two cell lines.