CTLA-4 is required for the induction of high dose oral tolerance

Mucosal and systemic administrations of high dose antigens induce long- lasting peripheral T cell tolerance. We and others have shown that high dose peripheral T cell tolerance is mediated by anergy or deletion and is preceded by T cell activation. Co-stimulatory molecules B7-1 (CD80)/B7-2 (CD86) and their counter-receptors CD28/CTLA-4 play pivotal roles in T cell activation and immune regulation. In the present study, we examined the roles of the B7 co-stimulation pathway in the generation of high dose peripheral T cell tolerance. We found that blocking B7:CD28/CTLA-4 interaction at the time of tolerance induction partially prevented T cell tolerance, whereas selective blockade of B7:CTLA-4 interaction completely abrogated peripheral T cell tolerance induced by either oral or i.p. antigens. These results suggest that CTLA-4-mediated feedback regulation plays a crucial role in the induction of high dose peripheral T cell tolerance.      

Morphological and functional changes in spinal ganglion neurons after epidural clopheline administration

The aim of this chronic experimental study performed in 16 dogs was to determine the effect of epidural infusion of 0.01% clopheline solution on the morphological and histoenzymological characteristics of spinal ganglion neurons. Daily infusions of clopheline at the dose of 15 mg/kg for 14 days caused a decrease in capillary permeability in the spinal ganglia at the injection site and its increase in the intact areas. This finding suggests the changes in the activity of the microcirculatory bed with a disturbed interaction in capillary-neuron system. Analysis of morphometric parameters has demonstrated the presence of some functional and reversible dystrophic changes in spinal ganglion neurons, which were associated with epidural infusion of both clopheline and isotonic solution of sodium chloride. Determination of the activity of oxidation-reduction enzymes, which reflect the course of aerobic and anaerobic processes in spinal ganglion neurons, has shown no significant differences between the groups of animals infused with or isotonic solution of sodium chloride. In conditions of chronic experiment no significant variations were found in RNA content in ganglionic cells at and outside the sites of infusion of clopheline and of isotonic solution of sodium chloride.     

Iliac mucosa changes in late periods after total colectomy in patients with syndromes of gastro-intestinal polyposis

We studied follow-up iliac mucosa biopsies from 11 patients with juvenile polyposis and 4 patients with familial adenomatous polyposis who had undergone total colectomy with mucosal proctoectomy with creation of straight ileoanal anastomosis. The biopsies that have been taken from the posterior wall of the terminal ileum show incomplete and focal neocolonic transformation of iliac mucosa. Nevertheless, in most cases iliac mucosa preserved its architectural and histochemical characteristics. Chronic inflammation in iliac mucosa is not typical for patients with polyposis.     

Pancreatic hormone amylin and integrity of the gastric mucosa

The paper presents experimental findings of some possible mechanisms of protective antiulcerous action of amyline. Amyline is the second beta-cell pancreatic hormone, which has been just recently discovered. The authors have studied the effects of amyline on gastric secretion, mast cell functions, mesenteric lymphatic microvascular contractility, i.e. on individual aggressive and protective factors of the gastric mucosa. Amyline has been found to inhibit basal acid gastric secretion and the secretion stimulated by vagal irritation. The peptide reduces the secretory activities of mast cells. Amyline given to animals increases the heparin saturation index of mast cells and decreases the degranulation index. Amyline-induced stabilization of mast cells appears to followed by the decreased release of histamine and other damaging substances. The stimulating effect of amyline on the contractile activity of mesenteric lymphatic vessels was recorded in rats. Amyline increases both the frequency and amplitude of their contractions. The increased lymph flow that is closely associated with microcirculation promotes the maintenance of tissue homeostasis. Therefore, the protective antiulcerous properties of amyline reduce the action of aggressive agents on the gastric mucosa and stimulate protective ones.     

Immunocytochemical demonstration of brain neurons using NeuN as a selective marker

The aim of the present study was to find optimal protocol of immunocytochemical reaction to NeuN nuclear protein for light and laser confocal microscopy, which would exclude the antigen heat unmasking procedure that results in deteriorating the state of the tissue and requires expensive adhesive-coated slides. Best preservation of the antigen was found to be provided by fixation in zinc-formalin and Bouin's fixative (for a period of less than 24 hrs). Two protocols allowing to avoid antigen heat unmasking procedure during demonstration of the NeuN neuronal label in paraffin sections by the light and confocal microscopy are presented.     

Morphological characteristics and immunophenotype of dendritic cells generated from monocytes of human peripheral blood

Morphological features and immunophenotype of mature dendritic cells (DC) generated from the monocytes of healthy donor blood after culture with GM-CSF and IL-4 with the addition of TNF, were studied using light and electron microscopy, as well as flow-cytometry. It was shown that DC were characterized by a number of morphological features such as: large size, eccentrically located nucleus, highly developed system of extensions, large vacuolated cytoplasm, prominent and activated Golgi complex and ribosomal apparatus. Mature DC are characterized by active surface expression of MHC and co-stimulatory molecules (MHC I, MHC II, CD40, CD80, CD86).     

The comparative characteristics of the safety,immunogenic activity and prophylactic potency of the adult and children types of live influenza vaccine in schoolchildren aged 7-14 years

In Russia for prevention of influenza in children, aged from 3 to 14 years, the children's live influenza vaccine (LIV), based upon A/Leningrad/134/47/57(H2N2) master strain (LIVI) is used. The need for double immunization appears to be one out of the faulties of this preparation. The study was aimed to comparing the safety, immunogenic activity and prevention of influenza by LIV for adults (LIVII) (A/Leningrad/134/17/57(H2N2 master strain) and LIVI in children aged from 7 to 17 years under similar administration schedule. The safety, the preventive efficacy, humoral and secretory immunity were studied. In total 2486 persons, including 539 children, twice inoculated with LIVI, 971 persons once inoculated with LIVII, and 840 treated by placebo were obserbed. From the data of the clinical observations during 7 days after immunization both vaccines appeared to be low reactogenic. The LIVII advantages in induction of the humoral and secretory antibodies in comparison with children's vaccine had been revealed. Both vaccines were highly efficacious, the efficiency of both preparations was more pronounced after serologic correction of the diagnosis. The results obtained permit to recommend the single immunization by the variant of LIV at the base on A/Leningrad/134/17/57/(H2N2) master strain for prevention of influenza in school children.     

Morphogenetic aspect of the influence of purified birch tar on skin

Changes of the histological structure of rat's skin were studied two weeks following the daily applications of native birch tar and of purified birch tar, devoid of the components that could be potentially dangerous for humans. The morphometric investigations were performed with the use of computer technologies on the apparatus-programme complex (DiaMorph, Russia). It has been established that the main morphological manifestations of specific dermatotropic activity of birch tar in the present experiment included: epidermal hypertrophy, hyperkeratosis, stimulation of the activity of all dermal cellular elements, intensification of blood supply, reduction of sebaceous glands. Analysis of morphological findings indicates the bioequivalence of the native and purified birch tar in terms of its specific dermatotropic activity.     

Structural basis for the regulation of the neuronal sensitivity

Using light and electron microscopy structural bases for intracellular, extracellular and integrative regulation of synaptic efficiency and neuron sensitivity were established in rat sensomotor cortex. Intracellular regulation is realized basically through modulation of postsynaptic components of the synapse, while extracellular one is provided by synaptic endings of "recurrent" axons on GABA-ergic relay and interneurons. Integrative regulation is realized by means of concentration of similar axonal terminals in restricted cortical area and arrangement of "neuromediatory" pool.     

Currently available blood saving methods in a patient at cardiac surgery under extracorporeal circulation

Different blood saving methods are analyzed in 2000 cardiac surgical patients undergoing coronary and vascular bypass surgery in 1993 to 2000. The basic blood saving methods are as follows: intraoperative autoreinfusion (normovolemic thermodilution), reinfusion of the patient's blood, preoperative autologous plasma donation in combination with aprotinine, aminocapronic acid, etc. An analysis revealed a decrease in homologous blood components intraoperatively. Red blood cell transfusion decreased from 100% in 1993 to 44% in 2000, fresh frozen plasma and platelet transfusions did from 98 to 39% and from 96 to 1%, respectively. Intraoperative homologous blood transfusion could be avoided in 70% of those undergone coronary bypass surgery.