Российский научный центр радиологии и хирургических технологий Минздрава РФ, Санкт-Петербург, Российская Федерация Соотношения субпопуляционного состава мононуклеарных клеток крови у 68 пациентов исследованы методом проточной цитометрии до и в течение первого месяца после трансплантации трупной печени с целью определения их возможного вклада в процессы приживления трансплантата. Полученные данные позволяют рассматривать изменения регуляторных Т-клеток после трансплантации как час-тный случай генерализованного смещения всего дифференцировочного процесса в лимфоцитопоэзе, начиная со стволовых гемопоэтических клеток и прелимфоцитов. Смещение сопровождается увели-чением юных гематопоэтических стволовых клеток, клеток предшественников лимфоцитарного ряда, клеток с ангиогенными свойствами и уменьшением большинства более зрелых дифференцирован-ных форм лимфоцитов. Ослабление «толерогенной» активности печени у больных в листе ожидания трансплантации печени и восстановление ее после трансплантации объяснено морфообразующим, трофическим механизмом. Основу этого механизма составляет увеличение в крови стволовых гемо-поэтических клеток и ангиогенных клеток, переносящих регенераторную информацию к трансплан-тату.Ключевые слова: трансплантация печени, лимфоциты, стволовые клетки, кинетика, дифференцировка клеток, морфогенез.
FEATURES OF SUBPOPULATION COMPOSITION OF BLOOD LYMPHOCYTES IN RECIPIENTS WITHIN THE FIRST MONTH AFTER LIVER TRANSPLANTATION
A.N. Shoutko, O.A. Gerasimova, L.P. Ekimova, F.K. Zherebtsov, A.M. Granov
Russian Scientifi c Center for Radiology and Surgical Technologies of the Ministry of Healthcare of the Russian Federation, St-Petersburg, Russian FederationRatios of subpopulations of mononuclear blood cells in 68 patients were registered by method of fl ow cytometry during one month before or after transplantation of a cadaveric liver with the aim of a comparative assessment of the contribution of cellular factors into graft acceptance. Results. The obtained data allow considering the changes of separate Treg subpopulation after transplantation as a partial outcome of generalized shift of the whole process of lymphocytes differentiation, involving hematopoietic stem cells and prelymphocytes. This shift is followed by an increase of young hematopoietic stem cells, precursors of lymphocytes, angiogenic cells, and by a concomitant reduction of the majority of more matured subpopulations of lymphocytes. Conclusion. Diminishment of «tolerogenic» liver activity of before transplantation and its restoration after the organ's replacement is explained by morphogenic/trophic mechanism. The basis of this mechanism is an increase in blood of hematopoietic stem cells and other cells transferring angiogenic and regenerative information to the graft.
Individual parameters of circulating hemopoietic stem cells (HSC) lymphoid origin were measured by cytofluorometry before treatment of patients with metastatic non-small cell lung cancer and were retrospectively compared with individual life span's (LS). The possibility of poor prognosis of treatment's results (LS
The mechanisms of antitumor effect of polychemotherapy and systemic radiation therapy in non-tumorocidal doses are considered in the article, the advantages and disadvantages of each of them are noted as well as the common points connecting them with each other. Equivalence of the therapeutic effect mediated by myelodepression is substantiated. Methods of systemic radiation therapy and technical solutions for their implementation are given. It is concluded that it is well tolerated and effective.
The earlier studies of some authors of this paper showed that, contrary to the theoretical expectations, the mortality rate of cancer patients treated with radio-or chemotherapy had not been changing monotonically with age, but experienced several repetitive cycles during the last 2-3 years of life [ESRB, 2004]. As the number of cases in this earlier investigation was limited, we tested the statistical validity of this finding using different data sets with a larger number of cases. For these purposes we investigated the survival curves for i) 3 different stages of breast cancer (T1N1-2M0 ,T2N1-2M0 ,T3-4N1-2M0) extracted from the Finnish Cancer Registry that covered a time period 1945-79(n=333) and ii) 12 different age groups of breast cancer (covering age interval 30-89 years) extracted from the U.S. Surveillance, Epidemiology and End Results (SEER) Registry (n=83536). Parametric methods were used to describe the survival curves by exponential functions (i.e., using one-compartment models with constant death rate k, or two-compartment models with k1 and k2 as death rates in each compartment), and harmonic function allowing for estimation of repetition period Tcycle of quasi-sinusoidal disturbances of the monotonic dumped exponential path. Nonparametric methods such as smoothing, spectral analysis, and a series of non-parametric tests were used to confirm the findings of parametric analyses and investigate statistical significance of the estimated periods. We found that there exists a life span region of 0-40 months in which fluctuations in survival curve and respective hazard rates are detectable. The period of such fluctuations, Tcycle, is in reciprocal relation with k value and varies within 5 -more, then 40 months. The Tcycle varies dependent on diagnosed cancer, or age at diagnosis. The Tcycle shows a maximum of 40-54 years-old subjects being described as n-order polynomial function of age. The Tcycle is shortening along as cancer stages increase. In the cases when the survival curves allow for decomposition into two compartments, associated with different rates of mortality k1 and k2, the Tcycle can be associated with k corresponding to dominant compartment. In view of this, the phenomenon of stable fluctuations in survival can be understood if to assume an existence of certain physiological processes correlated with or even defined by the probability of death. We formulate respective hypotheses about the relation of this phenomenon with regular predeath instabilities in physiological systems and first of all in stem and progenitor cells compartments of the hematopoietic system.
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