Functional asymmetry of the cerebral hemispheres: its role in the pathogenesis of ectromelia and melanoma in (CBAxC57BL/6)F1 mice.

The aim of the present work was to identify the role of functional asymmetry in the cerebral hemispheres in the pathogenesis of infectious and oncological pathology in (CBAxC57BL/6)F1 mice. Mice with lefthemisphere dominance of motor functions ("right-handers") were found to be more resistant to infection with ectromelia virus and to show slower growth of tumors after subcutaneous injection of B-16 melanoma than animals with right-hemisphere dominance of motor control ("left-handers"). Thus, this report provides the first evidence for the role of functional asymmetry of the nervous system in the pathogenesis of ectromelia and melanoma (B-16) in (CBAxC57BL/6)F1 mice.

[Functional asymmetry of the brain hemispheres: the role in pathogenesis of ectromelia and melanoma in (CBAxC57BL/6)F1 mice].

The object of the research was to identify role of functional nervous asymmetry in formation of pathology in experimental animals. The role of functional asymmetry of the brain hemispheres in development of ectromelia and melanoma at (CBAxC57BL/6)F1 mice was investigated. It has been established, that mice with domination of motor functions in the left hemisphere ("right-handed") are more resistant against infection with ectromelia virus, and melanoma B-16 grows more slowly in these mice as compated with animals with domination of motor functions of the right hemisphere ("left-handed"). Hence, for the first time the role of functional nervous asymmetry in pathogenesis of ectromelia and melanoma (B-16) in mice (CBAxC57BL/6)F1 is established.

Effect of transplantation of splenic lymphoid cells on functional activity of the immune and nervous system in experimental animals.

We studied the effect of transplantation of splenic lymphoid cells on functional activity of the nervous (orientation and exploratory behavior and expression of genes for interleukin-1beta, type 1 interleukin-1 receptor, and erythropoietin in the brain) and immune system (cellular and humoral immune response, proliferative activity of immunocompetent cells, and expression of cytokine genes in splenocytes) in syngeneic animals with different behavioral characteristics. Intravenous injection of the lymphoid fraction of splenocytes from donor mice with a certain behavioral pattern in the open-field test had a modulatory effect on vertical locomotor activity of syngeneic recipient mice. The increase or decrease in vertical locomotor activity due to transplantation of immunocompetent cells was accompanied by specific changes in mRNA level for erythropoietin receptor and type 1 interleukin-1 receptor in brain cells of recipient mice. The regulation of orientation and exploratory behavior was also accompanied by changes in functional activity of the immune system in recipient animals. It was manifested in modulation of proliferative activity of thymic and splenic cells and cytokine gene expression in splenocytes.

[Cytokine--factors of the neuroendocrine regulation].

The given review is devoted to studying of a role cytokine in immune, nervous and endocrine systems. Ways of cytokine action in a brain are described. Are discussed neurotrophic and behavioural effects cytokine in a brain and mechanisms of their action. Acentuated, that there are groups cytokine which mainly show activity, operating in immune system, other groups cytokine are most active in nervous system, carrying out neurotrophic, neuroprotection functions or expressed and are produced in endocrine system and in a greater degree function as hormones. New approaches to functional classification cytokine are discussed.

[Immunological indices in gastric cancer].

Immunological indices were assayed in 167 patients with gastric cancer. Tumor growth involved reduction in levels of neutrophil peroxide (p<0.05), CD3+ and CD19+-cells (p<0.05) as well as intensification of apoptosis of lymphocytes (p<0.05). As monocytic and granulocytic phagocytosis (p<0.001) and HLA-DR-expression in monocytes (p<0.001) diminished, and mitogen-induced proliferative activity of mononuclear cells suppressed (p<0.05), total and relative levels of CD8+-cells (p<0.05) and spontaneous proliferative activity of mononuclear cells (p<0.05) in peripheral blood increased. Such changes should not be reganded as expression of immunosuppression alone. Mechanisms of immunological failure inherent in tumor growth need to be investigated further.

Effect of transplantation of immunocompetent cell on orientation and exploratory behavior and cytokine gene expression in the brain of experimental animals.

Intravenous injection of adherent splenocyte fraction from donor (CBAxC57Bl/6)F(1) mice characterized by specific open-field behavior modified this behavior in syngeneic recipient mice. This was paralleled by appropriate changes in the levels of IL-1b and type 1 IL-1 receptor mRNA in the brain cells of recipient mice. Hence, we demonstrated the possibility of directed regulation of orientation and exploratory behavior in mice by transplantation of immunocompetent cells. Mononuclear phagocytes play an important role in this phenomenon.

[A state of immune system in patients with acute stroke].

Over the last years the data on the changes of immunological parameters in traumatic and pathological lesions of brain hemispheres has been obtained by neuroimmunology, a science investigating mechanisms, principles, regularities as well as interaction and integration of immune and nervous systems. However many aspects of the field remain unclear and need further study. In this context parameters of immune system in patients with acute stroke have been examined. These parameters proved to correlate with the disease severity suggesting that the main parameters of cell and humoral patterns of immune system depend on the structural and functional state of brain hemispheres.

[Immunogenetic prognosis and long-term results of surgery for gastric cancer].

A link between HLA allelic variants and long-term results of surgery for gastric tumors was established on the basis of a 10-years follow-up of 112 cancer patients (stage I-II--37.9, III-IV--62.1%; radical surgery--44.6%). HLA class I was studied in a lymphocytotoxic test; HLA class II--gene DRBI specificity using polymerase chain reaction of peripheral blood cell DNA. The control group included healthy subjects living in the city of Novosibirsk (n = 341). High frequency of antigens HLA-B41, -DR1, -DR7 (p < 0.01) co-occurred with HLA-A2, -B12, -B13 and -B18 presence (p < 0.05) in breast cancer patients. Clinical manifestations of cancer were shown to develop in HLA-A1, -B8, -B15, -DR3 and -DR5 carriers at early stages. Tumor development at later stages (III-IV) was associated with HLA-A2, -B12, -B17, -B35, -B41 and -DR7. A link was registered between lethality rate, on the one hand, and HLA-A3, -B22, and, in particular, DR4, on the other, while remission of more than 7-years--with HLA-A11, -B13, -B21 and -DR5. HLA-B22/DR3 phenotype involved worse prognosis in radically-treated patients whereas that of HLA-B8/DR3--a better one.

Immunomorphological characteristics of animals with different levels of orientation and exploratory behavior.

We revealed some relationships between the level of orientation and exploratory behavior, functional activity of the immune system, and structural and functional organization of the CNS in animals. Significant differences in brain morphology and expression of cytokine IL-1 beta, type I IL-1 receptor, and erythropoietin receptor genes in brain cells were detected in (CBA x C57Bl/6)F1 mice with different initial levels of orientation and exploratory behavior. Immunocompetent cells of mice with high and low levels of exploratory behavior differ by spontaneous and mitogen-induced proliferative activity. The formation of humoral and cellular immune response in these animals causes opposite changes in exploratory behavior and the type of these changes depends on the initial level of this behavioral reaction.

[Immunotherapy of lung tumors in Balb/c mice]. / Immunoterapiia opukholei lëgkikh u myshei Balb/c.

Tissue-specific immune reactions were used to develop a method of dealing with malignant tumors. Injection of proteins isolated from lung tissue of mice (CBAxC57BL/6)F1, of varying age, into mice Balb/c with urethane-induced lung tumors cut the number of such tumors by half. Direct correlation was found between the magnitude and nature of effect and level of lung protein injection.

[Adenocarcinoma of the stomach: clinical and immunologic features]. / Adenokartsinoma zheludka: kliniko-immunologicheskie osobennosti.

Lower natural killer cells activity (NKCA), varying stage of anemia and in vitro depressed colony-forming ability of committed precursors of hemopoiesis were identified in 50 gastric cancer patients. The patients with different patterns of the vegetative nervous system had tumors with a range of adenocarcinoma cell differentiation. A relationship was established between anemia stage, colony-forming ability of committed precursors of hemopoiesis, on the one hand, and vegetative nervous system pattern, stage of tumor cell differentiation and, to a less extent, NKCA, on the other.

Asymmetry of delayed type hypersensitivity reaction in mice.

The intensity of delayed type hypersensitivity reactions in the left and right paws was studied in mice divided into left- and right-pawed by the motor asymmetry of the brain. The reaction was more pronounced in the left paw in all animals irrespective of motor asymmetry. Motor asymmetry of the brain hemispheres little contributed to the manifestation of differences in the delayed type hypersensitivity reactions in the left and right paws. The authors concluded that asymmetry of cellular immunity is determined by functional asymmetry of cells in regional lymph nodes.

Modulation of orientation and exploratory behavior in mice during development of humoral immune response.

We demonstrated opposite changes in the orientation and exploratory behavior of (CBAxC57Bl/6)F(1) mice in the open field test during the formation of primary humoral immune response. These changes depended on initial behavioral activity: the exploratory behavior was suppressed in animals with initially high activity, stimulated in animals with medium reaction, and remained unchanged in mice with initially low activity. The detected changes in the exploratory behavior during the formation of immune response were leveled in the total population (not divided by initial behavioral status).

Functional asymmetry of the brain and bone marrow in hemopoiesis in (CBAxC57Bl/6)F(1) mice.

The role of functional asymmetry of the brain and bone marrow in the formation of exogenous 8-day splenic CFU was studied in (CBAxC57Bl/6)F(1) mice. The intensity of hemopoiesis depended on the motor asymmetry of donors and recipients of bone marrow cells and differed for bone marrow transplantations from the right and left femoral bones.

Cytokine gene expression in cerebral hemispheres and behavioral reactions of (CBAxC57Bl)F1 mice.

Interleukin-1beta mRNA, interleukin-1beta receptor mRNA, and erythropoietin receptor mRNA are expressed in the brain of (CBAxC57Bl)F1 mice. Immunization with sheep erythrocytes stimulated the expression of these cytokines in the cerebral hemispheres. Injection of recombinant erythropoietin reduced expression of interleukin-1beta, interleukin-1beta receptor, and erythropoietin receptor genes in the brain of experimental animals and considerably increased their motor activity in the open field test.

Modulation of orientation and exploratory behavior of (CBAxC57Bl/6)F1 mice by immunocompetent cells.

The present investigation develops a previously published concept on integration of the immune, endocrine, and nervous systems in a universal structural and functional block (IMEN system). Splenocytes from donor (CBAxC57Bl/6)F1 mice characterized by specific behavior in the open field test modified the behavior of syngeneic recipient mice after intravenous infusion.

[Expression of erythropoietin receptor mRNA in mouse brain hemispheres]. / Ekspressiia mRNK retseptorov éritropoétina v polushariiakh golovnogo mozga myshei.

Now there is a growing evidence that erythropoietin receptors (Epo-R) are present also in some nonhematopoietic tissues such as endothelial cells and fetal cells of neural origin, although the physiological role of Epo-R at these sites is unclear. There are some speculations that Epo-R may be expressed on cells only in the developing CNS. The objective of this study was to determine whether Epo-R mRNA may be expressed in the brain hemispheres of Balb/c mice of different age groups: 1) newborn mice, 2) young 2 months old mice, 3) old 1.8 year old mice. We also studied the in vivo effect of recombinant erythropoietin on the expression of Epo-R mRNA in the brain hemispheres of (CBA x C57BL)F1 mice by RT-PCR. We have detected the existence of Epo-R mRNA expression in brain hemispheres of all the groups, but in old mice this expression was significantly higher. We have discovered a decrease in Epo-R mRNA expression in brain hemispheres of (CBA x C57BL)F1 mice 24 h after in vivo administration of recombinant erythropoietin. The Epo-R mRNA expression in the left brain hemispheres of (CBA x C57BL)F1 was considerably higher than in the right one.

Asymmetry in cerebral hemispheres and thymus lobes during realization of humoral immune response in mice.

We studied the role of functional asymmetry in mouse brain and thymus in the realization of humoral immune response. We concluded that not only nervous system asymmetry, but also immune system asymmetry and the relationship between cerebral hemispheres and cells of the right and left thymus lobes play an important role in the regulation of immune response.

Functional asymmetry of thymus and the immune response in mice.

We have studied the capability of the mouse thymus for asymmetrical formation. Concanavalin A (Con A)-stimulated proliferation of thymocytes from the right and left lobes of the thymus appeared to be significantly different. The direction of the differences depends on the dominance of the brain hemispheres with regard to motor asymmetry. In mice with right-dominant hemispheres, thymocytes from the left lobe of the thymus demonstrate a higher level of Con A-stimulated proliferation than those from the right lobe. In mice with left-dominant hemispheres, we found the opposite dependence. The in vivo experiments showed that the properties of cells from the contralateral lobes of the thymus proved to be a deciding factor that defines the differences at the level of the immune response in recipient mice with left-dominant hemispheres. This effect was less pronounced in mice with right-dominant hemispheres. Further analysis showed that left and right-dominant hemisphere mice differ according to the immune response only if mice from both groups received cells from the left but not from the right lobe of the thymus. That is, in the formation of the immune response to sheep red blood cells, the functional asymmetry of both the brain and thymus is of great importance. The experiments show that brain hemispheres and cells from different lobes of the thymus are able to interact in the regulatory effect on the immune response. The injection of cells from the thymus lobe ipsilateral to the dominant hemisphere, results in a significant excess of the immune response in left-dominant hemisphere mice in comparison with the response of right-dominant hemisphere mice. It can be concluded that this work demonstrates, for the first time, the asymmetrical function of a bilateral immune organ--the thymus. The asymmetry is shown not only at the level of Con A-induced proliferative activity but also at the level of the influence on the humoral T-dependent immune response in mice. Besides, we have found the interaction of brain hemispheres and thymus lobes in the regulation of the immune response.