Kinetics of MHC class II and transferrin receptor expression by colostral cells stimulated in vitro with concanavalin A and myelin basic protein.

The colostral cells, regarded generally as being protective, have been shown to differ in a number of membrane properties (rosetting, adherence, mobility) from the corresponding peripheral blood mononuclear cells. After in vitro stimulation with Con A or MBP 50% to 70% of the human colostral cells appeared HLA-DR positive at the first 24 h of culturing. The CD71 expression reached a maximum on culture days 2-3 coinciding with the maximal proliferative response. With regard to the phenotypic characteristics and their kinetics, the human colostral cells did not show significant differences from the peripheral blood mononuclear cells.

Analysis of suppressor activity in experimental allergic encephalomyelitis inhibited by graft-versus-host reaction.

The induction of local graft-versus-host reaction (GvH) prior to the encephalitogenic challenge resulted in the conversion of acute experimental allergic encephalomyelitis (EAE) to the chronic-like EAE. This inhibitory effect of GvH on EAE development was cyclophosphamide (CY) sensitive. Cell-free supernatants of peripheral blood lymphocytes (PBL) isolated from guinea pigs with chronic-like EAE and during recovery from EAE showed suppressor activity on the in vitro proliferative response of myelin basic protein (MBP) sensitized PBL. The appearance of anaphylactic anti-MBP antibodies and a change in the ratio complement fixing: haemagglutinating (CF/HA) antibodies was also registered.

[Suppression of cellular immunity in patients with carcinoma in situ and microinvasive cancer of the cervix uteri]. / Supressiia kletochnogo immuniteta u bol'nogo s kartsinomoi in situ i mikroinvazivnym rakom sheiki matki.

Monoclonal antibodies (Ortho type) were used for immunocytochemical evaluation of cell-mediated immunity in peripheral blood from 29 patients with in situ (TisNoMo) and microinvasive (T1aNoMo) cervical carcinoma. The total number of T cells (OKT3+) was decreased in both patient groups compared to healthy volunteers. Marked difference between OKT4+ (helper/inducer) and OKT8+ (suppressor/cytotoxic) cells was observed OKT8+ level rose with advancement of disease, resulting in inverted OKT4+/OKT8+ ratio in T1aNoMo cancer patients. Antitumor immune resistance proved inhibited in both study groups manifesting itself in suppression of cell-mediated immunity.

Positive effect of cyclophosphamide on the expression of MHC class II antigens.

Wistar rats, 6-8 weeks old, were treated intraperitoneally (i.p.) with a single dose of 20 or 200 mg/kg cyclophosphamide (CY), one day before their immunization with 50 mg/kg ovalbumin (OVA). On the third day after CY administration, cytological slides from peritoneal cells, obtained by lavaging the peritoneal cavity and cryosection from the mesenterial lymph nodes and spleen were prepared. The slides were stained by the method of peroxidase-antiperoxidase with monoclonal antibodies OX6 (Sera-Lab) against constant region determinant of rat class II antigens. The results obtained demonstrated a strong hyperexpression of MHC class II antigens in the peritoneal cells as well as in the lymph nodes and spleen from animals treated with CY and a stronger one, when after CY administration the animals were immunized with OVA. However, immunization with OVA alone did not stimulate notable augmentation of Class II antigen expression compared to healthy nontreated animals. The hyperexpression of class II antigens in animals treated with CY resulted from a pronounced lymphocytes depletion. This suggests that it is not lymphocytic gamma-interferon, as is commonly accepted, but some other factor(s), released from the accessory cells, that takes part in the mechanism of class II antigen hyperexpression.

Abrogation of induced resistance to experimental allergic encephalomyelitis in guinea pigs by host-versus-graft reaction.

Experimental allergic encephalomyelitis (EAE) effector cells known to exist in guinea pigs with myelin basic protein-incomplete Freund's adjuvant (MBP-IFA)-induced resistance to EAE could be activated in vivo by means of allogeneic confrontation (local host-versus-graft reaction (HVGR)). The abrogation of the resistance was observed only when HVGR was combined with encephalitogenic challenge (myelin basic protein-complete Freund's adjuvant (MBP-CFA)) in a certain order and at certain time intervals. The injection of 20 x 10(7) gamma-irradiated allogeneic lymphoid cells 7 or 4 days prior to or along with MBP-CFA treatment resulted in development of EAE with delayed onset and protracted course. The effect was most prominent when HVGR was induced on day -4. Histological examination revealed inflammatory lymphoid cell infiltrations in spinal cord. Serum level of total and anaphylactic anti-MBP antibodies correlated with the clinical picture.

Anti-oxidant capacity of spinal cord and erythrocytes of guinea pigs in case of experimental allergic encephalomyelitis and after disease suppression.

In the lumbar spinal cord of EAE guinea pigs a significant increase in SOD activity, lipid hydroperoxides content (more than 60%) and Fe2(+)-ascorbate-induced lipid peroxidation was observed. Multiple injections of cytochrome C-vitamin B2-vitamin PP (CV-combination) during the disease latent period resulted in suppression of EAE development. Supplementation with vitamin C, vitamin B12 or ATP eliminated this suppressive effect. Upon treatment with CV-combination beginning on the day of the first EAE clinical signs a half of the sick animals recovered. In their erythrocytes the ratio between SOD and catalase activities was normalized, though on a higher level. In the lumbar spinal cord the concentration of lipid hydroperoxides was decreased to the control one. Oxidative damage of the central nervous system is one of the mechanisms underlying the pathogenesis of lethal EAE.

Interleukin production by human colostral cells after in vitro mitogen stimulation.

Human colostral cells were pulsed with PHA, Con A, or LPS and cultivated in serum-free medium. The culture supernatants were tested for IL-1 activity in C3H/HeJ thymocyte assay and for IL-2 activity on human lymphoblasts. The IL-1 activity was the highest at the 24th h of cultivation and IL-2 activity at the 48th h of cultivation.

Relationship between the effect of cyclophosphamide on adjuvant arthritis severity, skin allograft rejection and spleen cell cytotoxic activity in rats.

Cyclophosphamide, which has a poor immunosuppressive effect on adjuvant arthritis in rats, evokes an aggravating form of the disease when applied at a single low dose before rats' sensitization with complete Freund's adjuvant. However, cyclophosphamide administered by this method of treatment has no such enhancement effect on skin allograft rejection reaction; on the contrary, the rejection reaction was inhibited. Spleen cell cytotoxic activity against 51-Cr labelled chondrocytes significantly decreased in adjuvant arthritis, while in skin allograft rejection it increased during the latent period before the rejection reaction appeared. The addition of cyclophosphamide to the rats' treatment decreased more strongly spleen cell cytotoxic activity, especially in rats with adjuvant arthritis. We conclude that cyclophosphamide-sensitive spleen cytotoxic cells are playing a dual role in the pathogenesis of these two cell-mediated immunological processes: as immunosuppressive regulatory cells in adjuvant arthritis and as effector cells in skin allograft rejection reaction.

Modulation of experimental allergic encephalomyelitis by a host-versus-graft reaction: a clinicopathological study.

The effect of timing of a local host-versus-graft reaction on the induction of acute experimental allergic encephalomyelitis (EAE) was studied in guinea pigs. 20 x 10(7) gamma-irradiated allogeneic cells injected 4 days after encephalitogenic challenge resulted in the development of EAE with an earlier onset, an increased delayed-type hypersensitivity (DTH) response and an increase in lymphoid cell infiltration in the spinal cord. Challenge with allogeneic cells on days -4 and -7, however, produced a delay in onset and a protracted course of disease, with 30-40% of the animals recovering. Evidence of disease was confirmed histologically.

Induction of resistance to experimental allergic encephalomyelitis in newborn guinea pigs.

It was observed that treatment of mother guinea pigs with myelin basic protein (MBP) in encephalitogenic form during pregnancy (1) (5) and in nonencephalitogenic form during pregnancy and/or lactation (3) resulted in a temporary resistance to experimental allergic encephalomyelitis (EAE) in their offspring. The nature of the factor(s) transferred from the mother to the progeny and responsible for induction of the unresponsiveness to an EAE-provoking challenge at maturity, is not known. These might be antibodies, cells or tolerogenic fragments of the MBP molecule. The aim of the present study was to prove the possibility for active induction of resistance to EAE in newborn guinea pigs by their immunization with MBP or spinal cord homogenate (SCH) in nonencephalitogenic form. The stability of thus induced resistance was tested by cyclophosphamide (CY) and host versus graft reaction (HVGR).

Oxidation stability and fatty acid composition of selected storage and structural lipids: influence of different high fat diet compositions.

The oxidation stability of storage lipids from adipose tissue and of structural lipids from liver was compared to the coefficients of oxidizability of the pure fat used: lard (L); lard + sunflower oil 2:1 (LS); butter (B) and partially hydrogenated oil (H). The oxidation stability of the corresponding high-fat dietary regimens (50 energy-%) was also investigated. The experimental groups L, LS, B and H were compared to the control group (C) fed low-fat laboratory pellet-food. The coefficients of oxidizability were calculated from the fatty-acid composition of the used pure fats. The oxidation stability was performed in condition of accelerated oxidation under kinetic regimen, assaying the peroxide concentration in appropriate time intervals. The coefficients of oxidizability of dietary fats and storage lipids were very similar. This is explained by the fact that the fatty-acid composition of storage lipids reflected that of the corresponding high-fat diets. The oxidation stabilities in storage lipids were markedly lower than these in the respective dietary regimens. The highest oxidation stability in lipids from adipose tissue was found in group B, and the lowest in group LS. Contrarywise, the oxidation stability in liver lipid showed the following declining sequence: C greater than H greater than L greater than LS greater than B. The discrepancies in oxidation stability of the various specimens (pure fats, dietary fats, storage and structural lipids) may be explicated by an intervention of factors with pro- and anti-oxidative action. The large deviations in fatty acid composition in the examined tissues in comparison to the composition of the respective high-fat diets may also play an important role in this respect. These parallel studies on oxidation stability at different levels could improve our possibilities for evaluation of the stability and biological value of fats.

UV spectroscopy studies of the oxidation changes in depot and structural lipids in high-fat feeding.

The degree of incorporation of conjugated dienes, trienes and tetraenes into reserve (depot fats) and structural liver lipids of rats is studied depending on the type of high-fat feeding (50 energy%): lard, lard + sunflower oil (2:1), butter, hydrogenated sunflower oil. It is found that in adipose tissue there are only conjugated dienes whose concentration is lower than that of lipids of the respective diets and of the liver. Structural lipids are characterized by a high concentration of conjugated tri- and tetraenes. It is established that the fatty acid compositions of the diets and their oxidizability coefficients, respectively, do not correlate with the degree of accumulation of conjugated fatty acid structures in living organisms. The disequilibrated high-fat regimens based on butter and partially hydrogenated sunflower oil create conditions for more intensive incorporation of oxidized fatty acid products into the tissues.

[Indications for and the therapeutic action of hypolipidemic agents in patients with hyperlipoproteinemias]. / Pokazaniia i lechebno vuzdeistvie na niakoi khipolipidemichni sredstva pri bolni s khiperlipoproteinemii.

Seventy three patients with hyperlipoproteinemia (HLP) type II and IV were divided into three groups and treated with different pharmaceuticals. The first group was treated with 300 mg Radecol daily, the second--with 750 mg Probucol and the third--with 600 mg Bezalip. Best results in the patients with HLP, type II A, as regards the effect on total cholesterol were obtained in those treated with Probucol, in type II B the results from the treatment with Radecol and Probucol are similar. In type IV HLP the reduction of triglycerides is best manifested in those treated with Bezalip. The tolerance and indications for the treatment of the patients with the three preparations are evaluated with a view to individualization of the medicamentous treatment.

[Clinical research on the hypolipidemic action of a probucol preparation]. / Klinichni prouchvaniia vurkhu khipolipidmichnoto deistvie na preparata probukol.

Probucol is a drug with hypolipidemic effect from the group of diphenols. The preparation has been administered to 33 patients with hyperlipoproteinemia--15 with type IIA, 17--with IIB and 1--with type III, in a dose of 750 mg for 28 days. The following serum indices were studied: total cholesterol (TCh), cholesterol in lipoproteins with high density (Ch-HDL), triglycerides (Tg), percentage of free cholesterol FCh) and ester cholesterol (ECh) in HDL and lipid-acid composition of ECh in HDL and lipoproteins with low density (LDL). The preparation has a good tolerance. By the end of the treatment, TCh was significantly reduced in the patients with type IIA--with 28.4% (p less than 0.001) and in IIB--with 23.3% (p less than 0.001). Ch-HDL was reduced with 19% on the average in type II ChLD (p less than 0.001). An essential reduction of serum Tg was established--with 32.2%. Significant reduction of lipid acids in the composition of ECh and HDL was established in type IIA ChLD.

Effect of cyclophosphamide on thyroid gland in mice and guinea pig.

Male BALB-/c mice and guinea pigs were given cyclophosphamide (CY)-either a single dose of 20 or 200 mg kg-1 or multiple doses of 2 or 20 mg kg-1 daily for 10 days. On the 1st, 3rd, 7th and 15th day after the last dose the serum levels of TSH, T4, T3 and rT3 were measured by RIA. The thyroids were processed for light and transmission electron microscopy. Both acute and chronic administration of CY resulted in a significant and prolonged decrease of serum T4 levels in mice and guinea pigs. In contrast, significant increase of rT3 level was found after long-term administration of 20 mg CY kg-1 and single administration of 200 mg CY kg-1 to mice or guinea pigs, while no changes in T3 and TSH levels were found. The thyroid 131I organifications was inhibited. In follicular cells mitochondrial damage, distention and vacuolization of the endoplasmic reticulum cisternae were established. A period of 15 days was neither long enough for serum T4 to return to the normal level nor for the morphological characteristics of the thyroid to be restored.

The experimental obesity by high-fat feeding--a model for evaluation of the biological value of fats.

The experimental obesity by high-fat feeding of rats, introduced after weaning, was found to be a suitable model for evaluation of the biological value of nutritional fats with different fatty acid composition: butter (group B), lard (L), partially hydrogenated oil (H), lard + sunflower oil 2:1 (LS). The differences in the fatty acid composition of these regimens affect: the efficiency in creating the model of obesity; the hormonal pattern of blood plasma; some metabolic pathways in liver and adipose tissue (especially in group H); the fatty acid composition of some structural, reserve and transport lipids; some biological tests indicative of membrane's phospholipid and fatty acid composition, i.e. the rate of platelets aggregation. A special attention should be paid to the striking differences in the cellularity and morphogenesis of adipose tissue in group B (hyperplastic obesity) in comparison with all other high-fat groups (hypertrophic obesity), irrespective of the identical energy and protein content of the diets. Thus, the early administration of a diet with butterfat (50% of energy) promoted a model of hyperplastic obesity, while the isocaloric diet with lard + sunflower oil caused a hypertrophic type of obesity. The authors have proved the regenerating capacity of the periepididymal fat pad in adult rats after partial lipectomy. The relative contribution of endogenic and exogenic (nutritional) factors in this process is discussed and the modifications in the cellularity of adipose tissue on these conditions are evaluated.