13 research outputs found
Clinical, morphological and molecular biological examination of the myocardium in COVID-19 patients
The presence of coronavirus-associated myocarditis remains controversial despite elevations in cardiac troponin and natriuretic peptide in many patients.Aim.Β To assess the morphological changes in the myocardium of patients who died due to coronavirus disease 2019 (COVID-19) and compare them with the intravital level of cardiac biomarkers.MaterialΒ andΒ methods. A total of 420 hospital charts and 77 autopsies of those who died from COVID-19 were analyzed. In 15 of 77 cases (19%) with histologically suspected myocarditis, an immunohistochemical examination of the myocardium with antibodies to CD3, CD45, CD8, CD68, CD34, Ang1, VWF, VEGF, HLA-DR, MHC1, C1q, VP1 of enteroviruses was performed, and in 8 patients with immunohistochemically confirmed myocarditis (10%) β polymerase chain reaction for SARS-CoV-2.Results. Hemorrhage, intramural thrombosis, necrosis of non-coronary origin, myocardial infarction and lymphocytic myocarditis were detected in 43%, 10%, 17%, 19% and 10% of cases, respectively, without coronavirus N and E gene sequences in the myocardium. Dysplasia, hyperplasia and hypertrophy of the vascular endothelium, expression of Ang1, VWF, VEGF, MHC1, C1q, VP1 of enteroviruses were determined in 100, 100, 87, 100, 75 and 62% of cases of myocarditis, respectively. There were no significant correlations between inflammatory biomarkers and myocarditis.Conclusion. The main morphological manifestation of COVID-19 in the myocardium is the so-called endotheliitis with dysplasia and endothelial activation, leading to hemorrhages, intramural thrombosis and necrosis. There is no convincing evidence of a direct involvement of coronavirus in myocarditis induction
ΠΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½Π°Ρ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ° ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ: ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Ρ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠΈ ΡΡΠ°Π½Π΄Π°ΡΡΠ½ΠΎΠ³ΠΎ ΠΎΠ±ΡΠ°Π·ΡΠ° ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΡ Π³Π΅Π½Π° HER2
Cancer is the leading cause of death in the world. The development of oncopathology is closely related to various changes in the genetic material that occur in malignantly transformed cells. Medical decision-making requires a clear differentiation between normal and pathological indicators, which are, among other things, the results of application of quantitative methods in laboratory medicine. Studies of DNA isolated from a patientβs biological material, identification and measurement of the content of nucleotide sequences acting as oncopathology biomarkers allow to solve the problems of determining the genetic prerequisites for cancer, its early diagnosis, determining the treatment strategy, monitoring, and confirming the patientβs cure.The purpose of this research is to develop the main approaches to the design of DNA reference materials (RMs) for metrological support of molecular diagnostics of oncopathology through the example of the RM for the HER2 gene sequence content in the human genome, with the value of Β«the number of copies of the DNA sequenceΒ» which is metrologically traceable to the natural SI unit Β«oneΒ».In the course of the research, a technique for measuring the HER2 gene amplification (the number of copies of the gene sequence per genome) was developed based on the use of the digital PCR method (dPCR). Comparability of measurement results for the method developed by the authors, and the results obtained using a commercial kit by the MLPA method on samples of human biological material is shown.Five permanent cell lines obtained from the CUC Β«Vertebrate Cell Culture CollectionΒ» were characterized in relation to the copy number ratios of HER2 gene sequence and CEP17 and RPPH1 genes sequences. A cell line with the HER2 gene amplification was identified. The results obtained will be used to create the RM for the copy number ratio of the HER2 gene sequences and the RPPH1 and CEP17 gene sequences. Creation of matrix DNA RMs based on human cell cultures certified using dPCR will allow transferring the unit of copy numbers of the DNA sequence to calibrators included in medical devices, thereby ensuring the required reliability and comparability of measurement results in the laboratory diagnostics of oncopathology, as well as the possibility of calibrating routine methods of DNA diagnostics and intralaboratory quality control.ΠΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ ΡΠ²Π»ΡΡΡΡΡ ΠΎΡΠ½ΠΎΠ²Π½ΠΎΠΉ ΠΏΡΠΈΡΠΈΠ½ΠΎΠΉ ΡΠΌΠ΅ΡΡΠ½ΠΎΡΡΠΈ Π² ΠΌΠΈΡΠ΅. Π Π°Π·Π²ΠΈΡΠΈΠ΅ ΠΎΠ½ΠΊΠΎΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΠΉ ΡΠ΅ΡΠ½ΠΎ ΡΠ²ΡΠ·Π°Π½ΠΎ Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠΌΠΈ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡΠΌΠΈ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Π°, Π²ΠΎΠ·Π½ΠΈΠΊΠ°ΡΡΠΈΠΌΠΈ Π² Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎ ΡΡΠ°Π½ΡΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΊΠ»Π΅ΡΠΊΠ°Ρ
. ΠΡΠΈΠ½ΡΡΠΈΠ΅ ΠΌΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΠΈΡ
ΡΠ΅ΡΠ΅Π½ΠΈΠΉ ΡΡΠ΅Π±ΡΠ΅Ρ ΡΠ΅ΡΠΊΠΎΠΉ Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΠ°ΡΠΈΠΈ Π½ΠΎΡΠΌΠ°Π»ΡΠ½ΡΡ
ΠΈ ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Π΅ΠΉ, ΡΠ²Π»ΡΡΡΠΈΡ
ΡΡ Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ°ΠΌΠΈ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² Π² Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠ½ΠΎΠΉ ΠΌΠ΅Π΄ΠΈΡΠΈΠ½Π΅. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΠΠ, Π²ΡΠ΄Π΅Π»Π΅Π½Π½ΠΎΠΉ ΠΈΠ· Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Π° ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ°, Π²ΡΡΠ²Π»Π΅Π½ΠΈΠ΅ ΠΈ ΠΈΠ·ΠΌΠ΅ΡΠ΅Π½ΠΈΡ ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΡ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠ΅ΠΉ Π½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ΄ΠΎΠ², Π²ΡΡΡΡΠΏΠ°ΡΡΠΈΡ
Π² ΡΠΎΠ»ΠΈ Π±ΠΈΠΎΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² ΠΎΠ½ΠΊΠΎΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΠΉ, ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡΡ ΡΠ΅ΡΠ°ΡΡ Π·Π°Π΄Π°ΡΠΈ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠ΅Π΄ΠΏΠΎΡΡΠ»ΠΎΠΊ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΡΠ°ΠΊΠ°, Π΅Π³ΠΎ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ Π½Π° ΡΠ°Π½Π½Π΅ΠΉ ΡΡΠ°Π΄ΠΈΠΈ, ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΡΡΡΠ°ΡΠ΅Π³ΠΈΠΈ Π»Π΅ΡΠ΅Π½ΠΈΡ, Π΅Π³ΠΎ ΠΌΠΎΠ½ΠΈΡΠΎΡΠΈΠ½Π³Π°, ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠΆΠ΄Π΅Π½ΠΈΡ ΠΈΠ·Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ°.Π¦Π΅Π»ΡΡ Π΄Π°Π½Π½ΠΎΠ³ΠΎ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΡΠ²Π»ΡΠ΅ΡΡΡ Π²ΡΡΠ°Π±ΠΎΡΠΊΠ° ΠΎΡΠ½ΠΎΠ²Π½ΡΡ
ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ΠΎΠ² ΠΊ ΡΠΎΠ·Π΄Π°Π½ΠΈΡ ΡΡΠ°Π½Π΄Π°ΡΡΠ½ΡΡ
ΠΎΠ±ΡΠ°Π·ΡΠΎΠ² (Π‘Π) ΠΠΠ Π΄Π»Ρ ΠΌΠ΅ΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΎΠ±Π΅ΡΠΏΠ΅ΡΠ΅Π½ΠΈΡ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ ΠΎΠ½ΠΊΠΎΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΠΉ Π½Π° ΠΏΡΠΈΠΌΠ΅ΡΠ΅ Π‘Π ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΡ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ Π³Π΅Π½Π° HER2 Π² ΡΠΎΡΡΠ°Π²Π΅ Π³Π΅Π½ΠΎΠΌΠ° ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°, Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅ Π²Π΅Π»ΠΈΡΠΈΠ½Ρ Β«ΡΠΈΡΠ»ΠΎ ΠΊΠΎΠΏΠΈΠΉ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΠΠΠΒ» ΠΊΠΎΡΠΎΡΠΎΠ³ΠΎ ΠΌΠ΅ΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈ ΠΏΡΠΎΡΠ»Π΅ΠΆΠΈΠ²Π°Π΅ΡΡΡ ΠΊ Π΅ΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠΉ Π΅Π΄ΠΈΠ½ΠΈΡΠ΅ SI Β«ΠΎΠ΄ΠΈΠ½Β».Π Ρ
ΠΎΠ΄Π΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π° ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠ° Π²ΡΠΏΠΎΠ»Π½Π΅Π½ΠΈΡ ΠΈΠ·ΠΌΠ΅ΡΠ΅Π½ΠΈΠΉ ΠΊΠΎΠΏΠΈΠΉΠ½ΠΎΡΡΠΈ (ΡΠΈΡΠ»Π° ΠΊΠΎΠΏΠΈΠΉ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ Π³Π΅Π½Π° Π½Π° Π³Π΅Π½ΠΎΠΌ) Π³Π΅Π½Π° HER2, ΠΎΡΠ½ΠΎΠ²Π°Π½Π½Π°Ρ Π½Π° ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠΈ ΠΌΠ΅ΡΠΎΠ΄Π° ΡΠΈΡΡΠΎΠ²ΠΎΠΉ ΠΠ¦Π (ΡΠΠ¦Π ). ΠΠΎΠΊΠ°Π·Π°Π½Π° ΡΡ
ΠΎΠ΄ΠΈΠΌΠΎΡΡΡ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠΎΠ² ΠΈΠ·ΠΌΠ΅ΡΠ΅Π½ΠΈΠΉ Π΄Π»Ρ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π½ΠΎΠΉ Π°Π²ΡΠΎΡΠ°ΠΌΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠΈ ΠΈ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠΎΠ², ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ
Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΊΠΎΠΌΠΌΠ΅ΡΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π½Π°Π±ΠΎΡΠ°, ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΡΡΠ΅Π³ΠΎ ΠΌΠ΅ΡΠΎΠ΄ MLPA Π½Π° ΠΎΠ±ΡΠ°Π·ΡΠ°Ρ
Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Π° ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°.ΠΡ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΠΎΠ²Π°Π½Ρ ΠΏΡΡΡ ΠΏΠΎΡΡΠΎΡΠ½Π½ΡΡ
ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ
Π»ΠΈΠ½ΠΈΠΉ ΠΈΠ· Π¦ΠΠ Β«ΠΠΎΠ»Π»Π΅ΠΊΡΠΈΡ ΠΊΡΠ»ΡΡΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΏΠΎΠ·Π²ΠΎΠ½ΠΎΡΠ½ΡΡ
Β» ΠΏΠΎ ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΡ ΡΠΈΡΠ»Π° ΠΊΠΎΠΏΠΈΠΉ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠ΅ΠΉ Π³Π΅Π½Π° HER2 ΠΈ Π³Π΅Π½ΠΎΠ² CEP17 ΠΈ RPPH1. ΠΡΡΠ²Π»Π΅Π½Π° ΠΊΠ»Π΅ΡΠΎΡΠ½Π°Ρ Π»ΠΈΠ½ΠΈΡ Ρ ΠΏΠΎΠ²ΡΡΠ΅Π½Π½ΠΎΠΉ ΠΊΠΎΠΏΠΈΠΉΠ½ΠΎΡΡΡΡ Π³Π΅Π½Π° HER2. ΠΠΎΠ»ΡΡΠ΅Π½Π½ΡΠ΅ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ Π±ΡΠ΄ΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½Ρ ΠΏΡΠΈ ΡΠΎΠ·Π΄Π°Π½ΠΈΠΈ Π‘Π ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΡ ΡΠΈΡΠ»Π° ΠΊΠΎΠΏΠΈΠΉ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠ΅ΠΉ Π³Π΅Π½Π° HER2 ΠΈ Π³Π΅Π½ΠΎΠ² RPPH1 ΠΈ CEP17. Π‘ΠΎΠ·Π΄Π°Π½ΠΈΠ΅ ΠΌΠ°ΡΡΠΈΡΠ½ΡΡ
Π‘Π ΠΠΠ Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΠΊΡΠ»ΡΡΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°, Π°ΡΡΠ΅ΡΡΠΎΠ²Π°Π½Π½ΡΡ
Ρ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ΠΌ ΡΠΠ¦Π , ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΡ ΠΏΠ΅ΡΠ΅Π΄Π°Π²Π°ΡΡ Π΅Π΄ΠΈΠ½ΠΈΡΡ Π²Π΅Π»ΠΈΡΠΈΠ½Ρ ΡΠΈΡΠ»Π° ΠΊΠΎΠΏΠΈΠΉ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΠΠΠ ΠΊΠ°Π»ΠΈΠ±ΡΠ°ΡΠΎΡΠ°ΠΌ, Π²Ρ
ΠΎΠ΄ΡΡΠΈΠΌ Π² ΡΠΎΡΡΠ°Π² ΠΌΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΠΈΡ
ΠΈΠ·Π΄Π΅Π»ΠΈΠΉ, ΠΎΠ±Π΅ΡΠΏΠ΅ΡΠΈΠ²Π°Ρ ΡΠ΅ΠΌ ΡΠ°ΠΌΡΠΌ ΡΡΠ΅Π±ΡΠ΅ΠΌΡΡ Π΄ΠΎΡΡΠΎΠ²Π΅ΡΠ½ΠΎΡΡΡ ΠΈ ΡΠΎΠΏΠΎΡΡΠ°Π²ΠΈΠΌΠΎΡΡΡ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠΎΠ² ΠΈΠ·ΠΌΠ΅ΡΠ΅Π½ΠΈΠΉ Π² Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠ½ΠΎΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ΅ ΠΎΠ½ΠΊΠΎΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΠΉ, Π° ΡΠ°ΠΊΠΆΠ΅ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΠΊΠ°Π»ΠΈΠ±ΡΠΎΠ²ΠΊΠΈ ΡΡΡΠΈΠ½Π½ΡΡ
ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊ ΠΠΠ-Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ ΠΈ Π²Π½ΡΡΡΠΈΠ»Π°Π±ΠΎΡΠ°ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΠΊΠΎΠ½ΡΡΠΎΠ»Ρ ΠΊΠ°ΡΠ΅ΡΡΠ²Π°
Genetic instability and anti-HPV immune response as drivers of infertility associated with HPV infection
Funding Information: RFBR grant 17β54-30002, Ministry of Science and Higher Education of the Russian Federation (Agreement No. 075β15β2019-1660) to Olga Smirnova. Publisher Copyright: Β© 2021, The Author(s).Human papillomavirus (HPV) is a sexually transmitted infection common among men and women of reproductive age worldwide. HPV viruses are associated with epithelial lesions and cancers. HPV infections have been shown to be significantly associated with many adverse effects in reproductive function. Infection with HPVs, specifically of high-oncogenic risk types (HR HPVs), affects different stages of human reproduction, resulting in a series of adverse outcomes: 1) reduction of male fertility (male infertility), characterized by qualitative and quantitative semen alterations; 2) impairment of couple fertility with increase of blastocyst apoptosis and reduction of endometrial implantation of trophoblastic cells; 3) defects of embryos and fetal development, with increase of spontaneous abortion and spontaneous preterm birth. The actual molecular mechanism(s) by which HPV infection is involved remain unclear. HPV-associated infertility as Janus, has two faces: one reflecting anti-HPV immunity, and the other, direct pathogenic effects of HPVs, specifically, of HR HPVs on the infected/HPV-replicating cells. Adverse effects observed for HR HPVs differ depending on the genotype of infecting virus, reflecting differential response of the host immune system as well as functional differences between HPVs and their individual proteins/antigens, including their ability to induce genetic instability/DNA damage. Review summarizes HPV involvement in all reproductive stages, evaluate the adverse role(s) played by HPVs, and identifies mechanisms of viral pathogenicity, common as well as specific for each stage of the reproduction process.publishersversionPeer reviewe
Postpericardiotomy syndrome: the role of genetic factors in the pathogenesis of a systemic inflammatory response after open-heart surgery
Aim. To assess the predictive value of polymorphic variants analyzing of interleukin-6Β (IL-6)Β geneΒ in patientsΒ with postpericardiotomyΒ syndromeΒ (PPS) during open-heart surgery.Material and methods. The study included 200 patients. All patients were analyzed for acuteΒ phaseΒ Β parameters in serum,Β effusionΒ fluid andΒ regionΒ of IL-6Β gene promoter sequence.Results. When analyzing the effusion fluid, in 15% of patientsΒ with early PPS,Β in accordance with the Light RW criteria, transudate was detected. Application of the RothΒ BJΒ criteriaΒ increased thisΒ proportionΒ toΒ 32%.Β An increaseΒ Β in theΒ level of C-reactiveΒ proteinΒ (CRP), procalcitonin,Β andΒ adenosine deaminase (ADA) activity indicated a systemic inflammatory response. The viral genome of cardiotropic viruses was detected in the effusion fluid in 10-12% of patients with PPS. Scanning mutations in the IL-6 500 bp region revealed one polymorphism of -174G>C. The frequency ofPPSΒ in patientsΒ with differentΒ genotypes (-174GC,Β -174GG andΒ -174CC)Β did not significantly differ. An association of the -174GG genotype of the IL-6 gene with a high risk of developing systemic inflammation in open-heart surgery and more frequent postoperative infectious complications has been established. In addition, the -174GG genotype was more often detected in patients with late PPS (p=0,017). There was nocorrelation betweenΒ the occurrence of genotypes, as well as the distribution of IL-6 geneΒ and coronaryΒ obstructionΒ index. However, carriageΒ of the G allele was more often detected in patients with injury of left main coronary artery.Conclusion. The presence of the -174GG genotype of the IL-6 gene and cardiotropic viruses contribute to the systemic inflammation during cardiosurgical interventions in extracorporeal circulation, but do not have predictive value for the PPS development
HPV Type Distribution in Benign, High-Grade Squamous Intraepithelial Lesions and Squamous Cell Cancers of the Anus by HIV Status
The incidence of anal cancer is increasing, especially in high-risk groups, such as PLWH. HPV 16, a high-risk (HR) HPV genotype, is the most common genotype in anal high-grade squamous intraepithelial lesions (HSIL) and squamous cell carcinoma (SCC) in the general population. However, few studies have described the distribution of HR HPV genotypes other than HPV 16 in the anus of PLWH. HPV genotyping was performed by DNA amplification followed by dot-blot hybridization to identify the HR and low-risk (LR) genotypes in benign anal lesions (n = 34), HSIL (n = 30), and SCC (n = 51) of PLWH and HIV-negative individuals. HPV 16 was the most prominent HR HPV identified, but it was less common in HSIL and SCC from PLWH compared with HIV-negative individuals, and other non-HPV 16 HR HPV (non-16 HR HPV) types were more prevalent in samples from PLWH. A higher proportion of clinically normal tissues from PLWH were positive for one or more HPV genotypes. Multiple HPV infection was a hallmark feature for all tissues (benign, HSIL, SCC) of PLWH. These results indicate that the development of anal screening approaches based on HPV DNA testing need to include non-16 HR HPVs along with HPV 16, especially for PLWH. Along with anal cytology, these updated screening approaches may help to identify and prevent anal disease progression in PLWH
A study of comparability in AFLP profiling using a simple model system.
NRC publication: Ye
HPV Type Distribution in Benign, High-Grade Squamous Intraepithelial Lesions and Squamous Cell Cancers of the Anus by HIV Status
The incidence of anal cancer is increasing, especially in high-risk groups, such as PLWH. HPV 16, a high-risk (HR) HPV genotype, is the most common genotype in anal high-grade squamous intraepithelial lesions (HSIL) and squamous cell carcinoma (SCC) in the general population. However, few studies have described the distribution of HR HPV genotypes other than HPV 16 in the anus of PLWH. HPV genotyping was performed by DNA amplification followed by dot-blot hybridization to identify the HR and low-risk (LR) genotypes in benign anal lesions (n = 34), HSIL (n = 30), and SCC (n = 51) of PLWH and HIV-negative individuals. HPV 16 was the most prominent HR HPV identified, but it was less common in HSIL and SCC from PLWH compared with HIV-negative individuals, and other non-HPV 16 HR HPV (non-16 HR HPV) types were more prevalent in samples from PLWH. A higher proportion of clinically normal tissues from PLWH were positive for one or more HPV genotypes. Multiple HPV infection was a hallmark feature for all tissues (benign, HSIL, SCC) of PLWH. These results indicate that the development of anal screening approaches based on HPV DNA testing need to include non-16 HR HPVs along with HPV 16, especially for PLWH. Along with anal cytology, these updated screening approaches may help to identify and prevent anal disease progression in PLWH
HPV Type Distribution in Benign, High-Grade Squamous Intraepithelial Lesions and Squamous Cell Cancers of the Anus by HIV Status.
The incidence of anal cancer is increasing, especially in high-risk groups, such as PLWH. HPV 16, a high-risk (HR) HPV genotype, is the most common genotype in anal high-grade squamous intraepithelial lesions (HSIL) and squamous cell carcinoma (SCC) in the general population. However, few studies have described the distribution of HR HPV genotypes other than HPV 16 in the anus of PLWH. HPV genotyping was performed by DNA amplification followed by dot-blot hybridization to identify the HR and low-risk (LR) genotypes in benign anal lesions (n = 34), HSIL (n = 30), and SCC (n = 51) of PLWH and HIV-negative individuals. HPV 16 was the most prominent HR HPV identified, but it was less common in HSIL and SCC from PLWH compared with HIV-negative individuals, and other non-HPV 16 HR HPV (non-16 HR HPV) types were more prevalent in samples from PLWH. A higher proportion of clinically normal tissues from PLWH were positive for one or more HPV genotypes. Multiple HPV infection was a hallmark feature for all tissues (benign, HSIL, SCC) of PLWH. These results indicate that the development of anal screening approaches based on HPV DNA testing need to include non-16 HR HPVs along with HPV 16, especially for PLWH. Along with anal cytology, these updated screening approaches may help to identify and prevent anal disease progression in PLWH
Quantification of cells with specific phenotypes II: Determination of CD4 expression level on reconstituted lyophilized human PBMC labelled with antiβCD4 FITC antibody
This report focuses on the characterization of CD4 expression level in terms of equivalent number of reference fluorophores (ERF). Twelve different flow cytometer platforms across sixteen laboratories were utilized in this study. As a first step the participants were asked to calibrate the fluorescein isothiocyanate (FITC) channel of each flow cytometer using commercially available calibration standard consisting of five populations of microspheres. Each population had an assigned value of equivalent fluorescein fluorophores (EFF denotes a special case of the generic term ERF with FITC as the reference fluorophore). The EFF values were assigned at the National Institute of Standards and Technology (NIST). A surface-labelled lyophilized cell preparation was provided by the National Institute of Biological Standards and Control (NIBSC), using human peripheral blood mononuclear cells (PBMC) pre-labeled with a FITC conjugated anti-CD4 monoclonal antibody. Three PBMC sample vials, provided to each participant, were used for the CD4 expression analysis. The PBMC are purported to have a fixed number of surface CD4 receptors. On the basis of the microsphere calibration, the EFF value of the PBMC samples was measured to characterize the population average CD4 expression level of the PBMC preparations. Both the results of data analysis performed by each participant and the results of centralized analysis of all participants' raw data are reported. Centralized analysis gave a mean EFF value of 22,300 and an uncertainty of 750, corresponding to 3.3% (level of confidence 68%) of the mean EFF value. The next step will entail the measurement of the ERF values of the lyophilized PBMC stained with labels for other fluorescence channels. The ultimate goal is to show that lyophilized PBMC is a suitable biological reference cell material for multicolor flow cytometry and that it can be used to present multicolor flow cytometry measurements in terms of ABC (antibodies bound per cell) units. Β© 2015 International Society for Advancement of Cytometr