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Biomedical subjects

V A Lesnikov

Publications and source records attributed to V A Lesnikov.

At least 19 recordsLinked to original sources
PubMed2006

Protection of human and murine hepatocytes against Fas-induced death by transferrin and iron.

Recent studies in a murine model show that transferrin (Tf) interferes with Fas-mediated hepatocyte death and liver failure by decreasing pro-apoptotic and increasing anti-apoptotic signals. We show here in vitro in murine and human hepatocyte cell lines and in vivo in mice that Fas-induced apoptosis is modulated by exogenous Tf and iron. The results obtained with iron-free Tf (ApoTf), iron-saturated Tf (FeTf), and the iron chelator salicylaldehyde isonicotinoyl hydrazone (SIH) in its iron-free and iron-saturated (FeSIH) forms indicate that apoptosis-modulating effects of Tf are not mediated by iron alone. Both the Tf molecule and iron affect multiple aspects of cell death, and the route of iron delivery to the cell may be critical for the final outcome of cellular Fas signaling. Survival of hepatocytes 'stressed' by Fas signals can be manipulated by Tf and iron and may be a target for prophylactic and therapeutic interventions.

Aldehydes↗
PubMed1996

Unresponsiveness to human leukocytes in immunosuppressed mice by combined donor-derived human transferrin and antigens.

Previous work on the facilitation of xenogeneic and allogeneic bone marrow engraftment in irradiated mice and dogs with transferrins allowed the development of a model for induction of an apparently durable state of immunological unresponsiveness or 'tolerance' in chemically immunosuppressed mice. The system is based on the simultaneous and combined administration of donor-derived cell antigens, namely human leukocytes, and specific donor-derived or plasma pool human transferrin into BALB/c or C57BL/6 mice previously treated with prednisolone and cyclophosphamide on day 0 and day 1 of the experiment. A properly timed presentation of both donor-specific or plasma pool transferrin and leukocyte antigens into the mice on day 3 and day 16 of the experiment, in the course of initial restoration of their lymphohaemopoietic tissues and cells after severe immunosuppression, results 1-3 months later, in their inability to 'recognize' human donor lymphocytes and to mount an immediate or a delayed-type immune response against human antigens. This durable state of unresponsiveness was evaluated by a complement-mediated cytotoxicity assay, with a mixed lymphocyte culture method and confirmed by the abrogation of the humoral (antibody response to human erythrocytes) and of the cell-mediated (popliteal lymph node test) immune responses in vivo. Our findings demonstrate the capacity of human plasma-derived transferrins to induce a state of durable unresponsiveness (xenogeneic tolerance?) in mice when administered with human antigens in the course of regeneration of stem cells in the bone marrow and lymphatic organs.

Animals↗
PubMed1994

Pineal cross-transplantation (old-to-young and vice versa) as evidence for an endogenous "aging clock".

Circadian (night), chronic administration of melatonin and young-to-old pineal grafting into the thymus have provided evidence for the existence of an endogenous, primary and central "aging clock" in the pineal gland. The new model described here serves to definitely demonstrate that the replacement of the pineal gland of an old mouse with the pineal from a young, syngeneic donor mouse remarkably prolongs its life and, conversely, the "old" pineal transplanted into a younger mouse will considerably shorten its life span. Pineal cross-transplantation thus provides clear-cut evidence for the central role of the pineal gland in the initiation and progression of senescence. It offers a novel basis for interventions in the aging process.

Aging↗
PubMed1994

Pyrogenic activity of human native and human recombinant interleukins-1 beta: stabilization with albumin enhances the pyrogenic action of recombinant IL-1 beta delivered into the rabbit brain.

The pyrogenic potential of natural and recombinant human IL-1 beta in rabbits was found to be very similar when the substances were given intravenously. Under these conditions, stabilization of rIL-1 beta with human serum albumin (HSA) failed to affect the pyrogenic activity of recombinant IL-1 beta. When the two preparations were administered directly into the PO/AH area of the brain, recombinant IL-1 beta was less pyrogenic than its natural counterpart. This lower pyrogenicity of recombinant IL-1 beta was corrected if the injected material contained HSA, which is known to stabilize in vitro the biological activities of IL-1 beta against slow degradation. The possibility is now considered that the central and peripheral systems for IL-1 inactivation are different. The existence of an intrabrain IL-1 pool is suggested and its significance for neuroimmunomodulation is stressed.

Animals↗
PubMed1993

[The pyrogenic activity of native and recombinant human interleukin-1 beta].

Comparative doses (100-180 ng/kg) of highly purified human native interleukin-1 beta (nIL-1 beta) and human recombinant IL-1 beta (rIL-1 beta) intravenously injected were found to cause similar changes in body temperature in rabbits. Under these conditions, stabilization of rIL-1 beta by human serum albumin (HSA) fails to affect rIL-1 beta pyrogenic activity. nIL-1 beta, 0.05-2.0 ng, injected into the PO/AH region of the brain causes dose-dependent fever in the animals. With intrahypothalamic nIL-1 beta (versus i.v. injection), the pyrogenic activity of rIl-1 beta is much lower than that of nIL-1 beta. Moreover, pyrogenicity appears to be dependent on the type of rIL-1 beta, namely on free or stabilized by HSA. The former has about 100-fold and the latter a 25-fold lower activity than the native cytokine (in terms of a dose-pyrogenic effect relationship). The findings are discussed in the light of the existence of various interleukin IL-1 beta pools.

Animals↗
PubMed1992

The involvement of pineal gland and melatonin in immunity and aging: II. Thyrotropin-releasing hormone and melatonin forestall involution and promote reconstitution of the thymus in anterior hypothalamic area (AHA)-lesioned mice.

A stereotactic electrolytic lesion of the anterior hypothalamic area in mice produces a rapid involution of the thymus and a reduction of lymphocytes in the peripheral blood. This effect on the thymus and blood lymphoid compartment can be prevented by postoperational administration of thyrotropin-releasing hormone (TRH) or melatonin. These activities of TRH or melatonin are antagonized by the opioid receptor blocker naltrexone. They do not seem to depend on stimulation of the thyroid gland or of the endogenous opioid system but rather on a direct activity of TRH on thymic targets or binding sites on lymphocytes.

Aging↗
PubMed1991

Fever produced by intrahypothalamic injection of interleukin-1 and interleukin-6.

Pure human interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6), both of natural origin, were found to cause fever in rabbits when injected into the PO/AH region of the brain. The threshold dose required for this effect was between 0.4 and 4 U, equivalent to 0.04 to 0.4 ng for IL-1 beta, and around 50 U, equivalent to 0.05 ng for IL-6. From this it was estimated that this area of the brain responds to a local concentration of approximately 1 ng/ml of these cytokines, a level which can easily be reached after intravenous administration of threshold pyrogenic doses of either cytokine. The observation supports the view that fever induced by systemic endogenous production of IL-1 and IL-6 is due to a direct effect on the thermoregulatory center and may not require production of mediators, such as prostaglandins, at sites distant from the center.

Animals↗
PubMed1990

[Effects of syngeneic UV-irradiated blood transfusion on the hemopoietic function of the bone marrow in normal state and in craniocerebral injuries in mice].

Experiments on mice (CBA X C57 Bl6)F1 using endo- and exogenous cloning have shown that ultraviolet irradiation of blood enhances colony stimulating properties of plasma. Stimulation of colony formation occurs both in vitro, on direct contact of UV-irradiated blood plasma with bone marrow cells, and in vivo, upon this injection to the whole organism. In the latter case, increased migration of colony forming hematopoietic cells from the bone marrow can be noted. Single intravenous injection of syngenic UV-irradiated blood prevents inhibition of hematopoietic function of the bone marrow induced by closed brain injury.

Animals↗
PubMed1989

[Endogenous colony formation in closed craniocerebral trauma in mice].

The model of closed brain trauma in mice using stem hematopoietic cell cloning methods has shown inhibited endogenous spleen colony formation and reduced number of reticulocytes in blood circulation during early periods subsequent to traumatic procedure. Maximal inhibition of bone marrow function occurs 4 days after trauma and is accompanied by a dramatic reduction of thymus weight and cellularity. The observed changes in bone marrow function can be one of the important factors leading to lower resistance of the organism to infections during early periods after brain trauma.

Animals↗
PubMed1988

[Differentiation and a change in the sensitivity to antibrain serum of circulating colony-forming units under the action of thymic factors].

The rabbit anti-mouse brain serum (RAMBS) that interacts with SC-1 marked cells, rather than with thymocytes and bone marrow cells, inhibits most of the blood and bone marrow colony-forming unit (CFU) population. A commercial thymus preparation thymalin increases the granulocytopoietic activity of the circulating CFU and decreases their sensitivity to RAMBS in thymectomized and normal animals. Differentiation of circulating CFU remains unchanged in thymalin-treated mice after RAMBS administration, while CFU erythroid activity of nontreated animals is lowered. The revealed changes in the CFU differentiation and sensitivity to RAMBS confirm the assumption that SC-1 antigen may mark Thy-1 lymphocytes of their microenvironment, rather than CFU.

Adjuvants, Immunologic↗