Human Ovarian Tumor Cells Escape γδ T Cell Recognition Partly by Down Regulating Surface Expression of MICA and Limiting Cell Cycle Related Molecules

Background: Mechanisms of human Vc2Vd2 T cell-mediated tumor immunity have yet to be fully elucidated. Methods and Findings: At least some tumor cell recognition is mediated by NKG2D-MICA interactions. Herein, by using MTT assay and PI-BrdU co-staining and Western-blot, we show that these Vc2Vd2 T cells can limit the proliferation of ovarian tumor cells by down regulation of apoptosis and cell cycle related molecules in tumor cells. Cell-to-cell contact is critical. cd T cell-resistant, but not susceptible ovarian tumor cells escape cd T cell-mediated immune recognition by up-regulating pErk1/2, thereby decreasing surface MICA levels. Erk1/2 inhibitor pretreatment or incubation prevents this MICA decrease, while up-regulating key cell cycle related molecules such as CDK2, CDK4 and Cyclin D1, as well as apoptosis related molecules making resistant tumor cells now vulnerable to cd T cell-mediated lysis. Conclusion: These findings demonstrate novel effects of cdT cells on ovarian tumor cells

Mitral valve prolapse: «Much Ado About Nothing», or a real unsolved problem?

The paper discusses the modern state of the mitral valve prolapse (MVP) problem. Controversial and unresolved issues on terminology, diagnostics, and tactics for different MVP variants are considered on the basis of the “Heritable disorders of connective tissue” recommendations (2009) by Expert Committee, the Society of Cardiology of the Russian Federation (VNOK). The modern diagnostic criteria of MVP are discussed, as well as echocardiography-estimated MVP prevalence while using those diagnostic criteria, and the comparison of Framingham Heart Study results to the authors’ own data. The interrelation between autonomic dysfunction and MVP is assessed, and different approaches to the stratification of MVP complication risk are compared, based on the echocardiography results and clinical data. The modern methods of MVP treatment and management strategy are also described

SYSTEMIC INVOLVEMENT OF CONNECTIVE TISSUE AND THE HEART AS IMPORTANT CHARACTERISTICS OF PRIMARY MITRAL VALVE PROLAPSE

Aim. To evaluate systemic involvement of connective tissue (SICT) in young adultswith mitral valve prolapse (MVP) without significant mitral regurgitation (MR).Material and methods. We studied 78 asymptomatic young subjects (mean age19,7±1,6, 72% male) with MVP in comparison with 80 sex- and age-matchedhealthy subjects. We performed phenotypic examination of MVP patients andcontrol group subjects, and echocardiographic study to identify the minor heartanomalies. Longitudinal strain and strain rate (SR) were determined using spackletracking (Vivid 7 Dimension GE, EchoPAC’08).Results. We identified two clusters of patients with MVP. In the first cluster (17subjects, 28% of the MVP group) a significant reduction of longitudinal systolicstrain observed comparing to the control group and the second cluster (61 subjects,72%). Global strain in the second cluster did not differ significantly from the controlgroup. Echocardiographic study showed nonsignificant increase in the averagenumber of SICT points in the first cluster and highly significant increase of the minorheart anomalies’ number in this group of patients.Conclusion. Myocardial deformation assessment allowed to identify the signs ofcardiomyopathy in quarter of young asymptomatic patients with MVP. Increasingnumber of minor heart anomalies in the group with primary MVP and cardiomyopathyallows considering other valve prolapses, dilatation of major vessels, basal and thickLV chords as features of the SICT in primary MVP. A great number of minor heartanomalies in primary MVP may indicate a change in the heart extracellular matrixthat can cause the development of cardiomyopathy in primary MVP

Autonomous dysfunction in young patients with mitral valve prolapse and Marfanoid habitus

Aim. To assess autonomous regulation status in young patients with mitral valve prolapse (MVP), Marfanoid habitus (MH), and signs of systemic connective tissue involvement (SCTP). Material and methods. The study included 59 young men with MVP, MH, and SCTP. All participants underwent phenotypical and clinical examination, anthropometry, electrocardiography (ECG), echocardiography (EchoCG), Holter monitoring (HM) of ECG and blood pressure (BP), treadmill test, heart rate variability (HRV) assessment, and additional cardiovascular tests. Results. In patients with MVP, MH, and particularly SCTI, a significant decrease in daytime parameters of sinus arrhythmia was observed. These individuals were also characterized by significantly reduced spectral HRV parameters. A pathologic reaction to active orthostatic test was registered in 50% of the participants with MVP and MH. The overall assessment of autonomous regulation tests demonstrated the presence of abnormalreactions in more than 50% of MH individuals and in 80% of MVP patients. Conclusion. Autonomous dysfunction is common among young patients with MVP, MH, and SCTI

Left ventricular remodelling and diastolic dysfunction in mitral valve prolapse

Aim. To assess the severity and potential mechanisms of left ventricular (LV) myocardial remodelling and diastolic dysfunction in symptom-free young patients with mitral valve prolapse (MVP), but no arterial hypertension or significant mitral regurgitation. Material and methods. The study included 78 patients with MVP (mean age 19,7±1,6 years; 72% males). The control group, comparable by age and sex distribution, included 80 healthy people. Longitudinal diastolic strain rate (SRe) was assessed using the speckle tracking method (Vivid 7 Dim, EchoPAC’06, GE). Serum levels of transforming growth factors (TGF

MINOR HEART ANOMALIES

The paper attempts to revise the working classification of minor heart anomalies (MHA). It is proposed to exclude some syndromes and abnormalities which clearly have an independent clinical significance. The need for exclusion of prevalent normal variants, as well as anatomical and physiological characteristics of child’s heart, is justified. The inverse dynamics of selected MHA in older vs. younger age groups is demonstrated. The authors suggest that the current working classification should be modified

VEGETATIVE DYSFUNCTION AND REPOLARIZATION DISORDERS ON RESTING ECG AND IN EXERTION IN YOUNGER PERSONS WITH MARFANOID PHENOTYPE AND MITRAL VALVE PROLAPSE

Aim. To estimate the prevalence of disordered repolarization and its relation with the character of vegetative dysfunction in younger persons with MP and MVP.Material and methods. Totally 285 persons studied of the young age (mean age 19,4+1,4 y.). Phenotypical, anthropometric and clinical investigation performed, ECG, EchoCG, Holter monitoring (HM) of ECG and BP, treadmill test. The heart rate variability (HRV) was assessed, cardiovascular tests performed.Results. MP and MVP are the most common dysplastic phenotypes in younger persons and have 15% ad 10% prevalence, respectively. The analysis of the treadmill test results, done for 140 of participants (80 males) showed that the youths studied had good tolerance of physical exertion (PET at the average or high level). In men with MVP and MP comparing to almost healthy individuals there was tendency to the decrease of PET and slowed down recovery of BP and pulse rate, that witnesses the decrease of adaptation abilities in the assessed persons of those groups. Disordered repolarization on resting ECG and during exercise test was found in MVP and MP, as in controls. However, the prevalence of T inversion during exercise test in MVP and MP was much higher, than in controls. HRV and vegetative tests analysis did not reveal significant differences in vegetative regulation in persons with EVRS on resting ECG and in the group of DR with PE

Diagnostics of inherited connective tissue disorders: achievements and future directions

The paper reviews general factors underlying the variety of clinical manifestations of inherited connective tissue disorders (ICTD). The authors make an attempt to harmonise the existing ICTD terminology with the standard international classification. It is proposed to use the Russian term “dysplasia” as a synonym of ICTD and to divide all ICTD into inherited syndromes (IS) and dysplastic phenotypes. An example of fibrillinopathies is used to consider the clinical polymorphism and genetic heterogeneity of IS. The clinical significance of Marfanoid habitus as a phenotype is also discussed