[Treatment of thrombotic thrombocytopenic purpura].

The review discusses approaches to treatment of congenital thrombotic thrombocytopenic purpura (TTP) or Upshaw-Schulman syndrome. In congenital TTP, plasma transfusions are sufficient. Such treatment options as plasma exchange, administration of clotting factor VIII concentrate, recombinant ADAMTS13, are also used. Separately discussed issues of management of patients with TTP during pregnancy, and pediatric patients with TTP.

[Treatment of thrombotic thrombocytopenic purpura].

The review discusses approaches to treatment of acquired thrombotic thrombocytopenic purpuгa (aTTP). In patients with aTTP plasma exchanges, glucocorticosteroids allow to stop an acute attack of TTP, and use of rituximab allows to achieve remission. In recent years, caplacizumab has been used. Treatment options such as cyclosporin A, bortezomib, splenectomy, N-acetylcysteine, recombinant ADAMTS13 are also described. Separately discussed issues of management of patients with TTP during pregnancy, and pediatric patients with TTP.

[Results of hematopoietic cell transplantation in the first complete remission in children with acute myeloid leukemia from an intermediate risk group].

AIM: To analyze the results of allogeneic and autologous hemopoietic cell transplantations (allo- and auto-HCT) in children with acute myeloid leukemia (AML) from an intermediate risk group, most of which were performed using lower-intensity conditioning modes. SUBJECTS AND METHODS. The study enrolled 36 children from an intermediate risk group, who had undergone auto-HCT (n = 22) or allo-HCT (n = 14) in December 1994 to December 2008. The patients' age was 0.7 to 16.6 years (median 12.8 years). Chemotherapeutic conditioning regimens were applied to all the patients. Melphalan was a basic myeloablative agent in 83.3% of cases. RESULTS: With a median follow-up of 4.6 years (1.1-13.8 years), three-year relapse-free survival (RFS) was 80.4%; overall survival (OS) was 65.6%. Recurrences were documented only in 6 (16.6%) patients from the auto-HCT. Transplantation-associated mortality (TAM) was 13.8% (five patients died). After allo-HCT versus auto-HCT, RFS, OS, and TAM were 100 and 68.7% (p = 0.03), 93.2 and 55.5% (p = 0.02), and 7.1 and 18.2%, respectively. Acute and chronic graft-versus-host reactions developed in 57.1 and 23.1%, respectively. CONCLUSION: Transplantation of allogeneic hemopoietic cells from a compatible related donor in the intermediate risk group children with AML, by using melphalan-based conditioning regimen, demonstrates a high survival rate with the minimum toxicity.

[Transplantation of the bone marrow from a HLA-compatible unrelated donor after immunoablative conditioning in children with acquired aplastic anemia unresponsive to combined immunosuppressive therapy: preliminary results].

AIM: To analyze the efficiency of transplantation of the bone marrow from a HLA-compatible unrelated donor and continued immunosuppressive therapy (IST) in children with aplastic anemia (AA) unresponsive to 2 courses of IST. SUBJECTS AND METHODS: The study enrolled 14 children aged 2-16 years (median 9 years). A control group comprised 26 patients in whom IST was continued. The median interval between the diagnosis of AA and transplantation was 26 months (9-156 months). The conditioning regimen consisted of thoracoabdominal irradiation in a dose of 2 Gy, fludarabin (Flu) 100-150 mg/m2, cyclophosphamide (Cy) 100-200 mg/kg, antithymocyte globulin (ATG) in 11 patients and Flu, Cy, and ATG in 3. A graft-versus-host reaction was prevented with mycophenolate mefetil in all the patients, tacrolimus in 11, and cyclosporin A in 3. Donors were compatible for high-resolution typing of 10/10 and 9/10 alleles in 8 and 6 patients, respectively; the source of a transplant was bone marrow in 13 patients and granulocyte colony-stimulating factor-mobilized peripheral blood precursors in one case. RESULTS: Thirteen patients achieved primary engraftment after single transplantation; one patient did after repeat transplantation. Grades I to II graft-versus-host reaction (GVHR) developed in 9 patients; postengraftment life-threatening infections in 3, extensive chronic GVHR in 2, circumscribed GVHR in 7. All fourteen hemopoietic cell transplant recipients followed for a median 17.5 months (range 1-71 months) were survivors. CONCLUSION: The likelihood of good survival after unrelated transplantations in AA is much higher than that after continued IST: 100% versus 15 +/- 11%.

[Reaction of the testicles of old animals on administration of human fetal tissues].

The aim of the work was to study the effect of fetal tissues on histological structure of testicles of the old mice. The data obtained suggest that the implantation of human fetal tissues postponed age degeneration of tissues.

Specific features of the immune response in old recipient mice to cell therapy.

Implantation of somatic cells from autopsy specimens (15-18 weeks gestation) had a modulatory effect on immunogenesis in old mice. Activation of the immune system in recipient animals after administration of somatic cells reflects a multistage influence of test preparation. The observed changes were reversible. A progressive decrease in activation of the immune system in recipient mice was not accompanied by the development of pathological changes. Repeated implantation was required to maintain these processes.

Embryological approach to studies of stem cells.

Based on the findings of their own studies on embryonic histogenesis of human tissues and published reports, the authors determined the time limits of the existence of human embryonic stem cells and type of their determination in divergent development of tissues in different organs. Realization of genetic information of embryonic stem cells during tissue embryogenesis was studied. This information is realized by the cambium. Variability of all tissue processes is possible only within their own embryonic primordium; prospects of the mesenchyma development in an adult body is discussed.

New data on the involvement of ectodermal epithelium in extrathymic differentiation of human T-lymphocytes.

Thymalin accumulates only in young cells of the skin ectodermal epithelium and mucosa of the anterior portions of the digestive and respiratory systems. After appearance of keratin the cells no longer accumulate thymalin. Similarly as in the thymus, thymalin content in the ectodermal epithelium of the organs is subjected to age-associated involution.

Thymalin in developing respiratory organs of human fetus.

We studied the appearance of immunomodulator thymalin in human respiratory organs during early embryogenesis. Thymalin accumulated in young cells of airway epithelium. In the alveolar part thymalin-positive cells were diffusely spread. Mature T cells (CD3+) and the main regulatory elements (CD4+ and CD8+) were detected during the same period in the lungs in the absence of thymic microenvironment. The function of immune elements forming in fetal lungs is local protection of the fetus from potentially aggressive maternal cells and infectious agents entering the body through the trachea and fetal blood vessels.

Thymic hormones in human fetal skin epidermis.

Thymic hormone thymalin is detected in young epidermal cells of human fetuses. Its content varies with gestation age. Maturation of keratinocytes in the epidermis is paralleled by a decrease in the population of young thymalin-positive cells. By birth they are located on the basal membrane and in some adjacent layers. This regularity was seen in different parts of the body.

Age-related changes of thymalin content in human epidermis.

Immunomorphological analysis revealed the presence of thymalin in human epidermis and in fetal reticuloepithelium. These structures are developed from the common embryonic primordium ectoderm. In embryos and adult humans thymalin is present only in young epidermal cells, which undergo age-related involution. By the age of 70 years, the layer of thymalin-containing cells looks thinned and discontinuous. The content of thymalin, a thymic factor, decreases with age.

[Immunologic characteristics of the thymus of aged CBA mice after implantation of human fetal tissue]. / Immunologicheskaia kharakteristika timusa starykh myshei linii CBA posle implantatsii fetal'nykh tkanei cheloveka.

The effect of human fetal tissues (hypothalamic, liver, spleen, adrenal, ovarian, testicle, uterine, prostatic, gut, placental cells) collected from the fetuses at the 16-22 weeks of prenatal development, on the cytological structure of the thymus of 2-years old CBA mice in 7, 14, 42 and 64 days after start of treatment has been studied using morphological and immunological methods. The data obtained suggest that the implantation of human fetal tissues does not stop totally, but postponed age involution of thymus.

[The order of lymphatic organs involvement in developing immune system of human fetus and its significance in perinatal pathology]. / Posledovatel'nost' vstraivaniia limfoidnykh organov v razvivaiushchuiusia immunnuiu sistemu ploda cheloveka i ee znachenie v perinatal'noi patologii.

The liver, thymus, spleen, lymph nodes, palatine and pharyngeal tonsils, appendix and Peyer's patch were studied by morphological and immune methods in more than 100 human embryos of 3 to 34 weeks of development. The order of some organs development in the immune system is established. Key periods in the development of the thymus (5-12 weeks) and 18 weeks when peripheral organs enter the immune system are specified. Inherited perinatal pathology in abnormal lymphocytic composition in the organ is illustrated by the appendix.

[Expression of endometrial proteins in the uterine glands in physiological and non-developing pregnancy]. / Ekspressiia éndometrial'nykh belkov v matochnykh zhelezakh pri fiziologicheskoi i nerazvivaiushcheisia beremennosti.

It is established that at the 1st trimester of the progressing pregnancy uterine glands produce both endometrial proteins (placental al-microglobulin--PAMG) and alpha 2-fertility microglobulin (AFMB) but with different intensity: maximum level of PAMG is at early periods (4-5 weeks) but 8-9 weeks of gestation for AFMB. Production deficiency of PAMG and AFMB in the glands epithelium is found in 90% cases of non-developing pregnancy (4-7 weeks) and this is obviously one of the causes of early pregnancy interruption.

Development of endocrine and lymphocytopoietic functions of the thymus in human embryogenesis.

The endocrine function of the thymus develops earlier than lymphocytopoietic. Thymalin is produced by epithelial cells in the thymus primordium. It is released into the blood and regulates differentiation of T lymphocytes in the liver, the initial hemopoietic organ. The hormonal and lymphopoietic functions of human thymus are united on weeks 7.5-8 of embryonic life.

[Biological capabilities of the thymus of human fetus during normal development and during constant exposure to small doses of radiation after the accident at the Chernobyl power plant]. / Biologicheskie vozmozhnosti timusa ploda cheloveka v usloviiakh normal'nogo razvitiia i pri postoiannom vozdeistvii malykh doz radiatsii posle avarii na Chernobyl'skoo AES.

The literature information and the authors's data are presented on the lability of human fetus thymus changes under extremal conditions. In particular, the source of the thymus development is discussed determining its morphogenetic potencies, the sequences of its endocrine and lymphocytopoietic function appearance. Lymphocytes composition and kinetics of their quantity in the process of fetus development and thymus response to the unfavourable conditions of the mother are presented.