Enhancement by mild cold stress of the antibody forming capacity in euthymic and athymic hairless mice.
Explore the source record for details and available documents.
Acclimatization↗
Biomedical subjects
M Holub
Publications and source records attributed to M Holub.
Simultaneous intracranial and extracranial recording of interictal epileptiform activity in patients with drug resistant partial epilepsy: patterns of conduction and results from dipole reconstructions.
Ten patients with complex partial epileptic seizures undergoing invasive video/EEG-monitoring were recorded with a combination of 10 subdural strip electrode contacts (subtemporal + lateral temporal), and 22 extracranial recording sites. In each patient several spikes with different intracranial distributions were identified, and spikes with similar distributions were averaged together with their extracranial activity. Dipole analysis of the extracranial activity was performed with the BESA program (Scherg, Garching Instrumente, München). In the horizontal plane subtemporal spikes gave oblique posterior, and lateral temporal spikes straight lateral or oblique anterior dipole orientations. In the coronal plane all spikes had an elevated orientation, most pronounced for medial subtemporal spikes. Dipole locations did not separate as well as dipole orientations. In our opinion our results would be difficult to explain without postulating a substantial degree of volume conduction from deep temporal areas to the surface. We conclude that dipole analysis of the interictal epileptiform activity does provide substantial information about which parts of the temporal lobe are involved in the epileptogenic process, making the method a useful tool in the preoperative investigation of patients with drug resistant partial epilepsy.
Adult↗
Autoimmune reactions induced by gliadin.
Explore the source record for details and available documents.
Animals↗
The importance of the hydroxyl moieties for inhibition of the Ca(2+)-ATPase by trilobolide and 2,5-di(tert-butyl)-1,4-benzohydroquinone.
Trilobolide and 2,5-di(tert-butyl)-1,4-benzohydroquinone (BHQ) are potent inhibitors of the Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum. Desoxytrilobolide and 2,5-di(tert-butyl)-1,4-diacetylphenol (acetyl-BHQ) have much lower potencies than their parent compounds and 2,5-di(tert-butyl)-1,4-benzoquinone (BQ) has no effect on ATPase activity. Studies using the ATPase labelled with 4-nitrobenzo-2-oxa-1,3-diazole (NBD) suggest that both trilobolide and BHQ bind more strongly to the E2 conformation of the ATPase than to the E1 conformation. Desoxytrilobolide, acetyl-BHQ and BQ have little effect on the E1/E2 equilibrium. Studies with mixtures of trilobolide and desoxytrilobolide suggest that the inactive derivatives are unable to bind to the ATPase.
Adenosine Triphosphatases↗
Cold-induced changes in brown adipose tissue thermogenic capacity of immunocompetent and immunodeficient hairless mice.
Mild cold acclimation (22 degrees C, 3 weeks) of hairless mice was shown to increase 5-fold the brown adipose tissue uncoupling protein content in immunodeficient BALB/c nu/nu mice, but by only 2.3-fold in immunocompetent BFU mice. The difference in activation of brown adipose tissue thermogenic capacity was due to a 2-fold increase in the content of brown adipose tissue in nu/nu mice only, which was paralleled by an increase in brown adipose tissue protein but not DNA content. Likewise, only in nu/nu mice the cold acclimation increased the reaction of natural killer cells in blood and peritoneal exudate with a shift from spleen to lymph nodes and increased the phagocytic index. The results indicate that the immune system may influence the defence against cold at the level of brown adipose tissue thermogenesis.
Acclimatization↗
Immunological properties of heterozygous nu/+ mice: changes in antibody response and inducibility of tolerance to protein antigens.
Heterozygous nu/+ mice are not fully identical in their immunological properties with the mice of wild +/+ genotype. A colony of nu/nu, nu/+ and +/+ mice from the same breeding nucleus was established and their immune reactivity to human serum albumin, inducibility of adult immune tolerance to hen egg lysozyme (HEL), sensitivity of their lymphoid cells to stimulation by mitogens and ratio of CD3, CD4 and CD8 positive cell populations was studied. Both the numbers of antibody-forming cells in regional lymph nodes and the antibody titres in sera of nu/+ mice were highly variable, between undetectable values of nu/nu and high values of +/+ homozygotes. Intravenous pretreatment with soluble HEL, leading in +/+ mice to a deep hyporeactivity to subsequent immunization with the same antigen, did not decrease the response of nu/+ mice significantly. These results indicate that the immunological alteration of nu/+ mice is not only quantitative and that T cell subpopulations might be differentially modified by the presence of nu allele. The finding of decreased CD4:CD8 ratio in nu/+ mice also supports this idea.
Animals↗
Influence of anti-inflammatory drugs on adhesion of neutrophils to endothelial cells cultured on microcarriers: a novel in vitro system as an alternative to animal experimentation.
Pharmacological control of inflammation by steroidal (SAIDs) and nonsteroidal (NSAIDs) antiinflammatory drugs is of substantial clinical importance. To reduce the number of animals used in pharmacological and toxicological evaluation of these drugs we developed a novel assay to determine adhesion of bovine neutrophils (PMN) to bovine aortic endothelial cells (BAEC) cultured on microcarriers in a flow-through system. Pretreatment of BAEC with thrombin (10(-7)-10(-4) M) led to a dose-dependent increase of PMN-adhesion (10(-6)-10(-4) M:P < 0.05); platelet-activating factor (10(-9) M) and 1:200 diluted zymosan-activated serum (ZAS) had similar effects (P < 0.001). Pretreatment of PMN with SAIDs (50.9 and 509 microM dexamethasone, 12.2 and 24.4 microM flumethasone) did inhibit adhesion to ZAS-treated BAEC dose-dependently. Pretreatment of PMN with NSAIDs had a less consistent influence on adhesion to ZAS-stimulated BAEC. While phenylbutazone (0.33 and 3.3 mM), diclofenac (0.392 and 0.574 mM), indomethacine (0.436 and 0.872 mM), and acetylsalicylic acid (3.47 and 16.94 mM) induced dose-dependent inhibition of PMN-adhesion to ZAS-treated BAEC, piroxicam (0.377 and 0.754 mM) inhibited PMN-adhesion strongly (P < 0.001) but not dose-dependently, and ketoprofene (0.614 and 1.228 mM) had no effect on PMN-adhesion. The method presented here is efficient for evaluating the pharmacological modulation of PMN interaction with endothelial cells, and useful for studying further aspects of endothelial cell biology.
Animal Testing Alternatives↗
Hairlessness does not influence growth retardation in nude mice. Computer image analysis study.
Ossification in 4-week-old nu/nu and nu/+ BALB/c and BFU mice was studied by X-ray analysis and by measurement of the thickness of the proximal tibial growth cartilage using CUE 4 Olympus computer image analysis. Not only altered architecture but also a significantly thinner proximal tibial growth plate was observed in athymic nu/nu as opposed to nu/+ and BFU mice. On the other hand, no significant differences were found between nu/+ and BFU littermates. Higher X-ray density of tail vertebrae was observed in nu/+ and BFU than in nu/nu mice. This comparison between athymic nu/nu and hairless euthymic BFU mice indicates that altered postnatal ossification in nude mice is not caused by hairlessness, but is due to other (immunological or endocrinological) differences.
Animals↗
Effect of ambient temperature on phenotype and functions of professional phagocytes of athymic nude mice.
Cytofluorometric analysis of surface marker expression was performed on myeloid cells isolated from bone marrow, spleen and lymph nodes of nude mice and nu/+ and +/+ mice (haired controls) exposed for various time periods to ambient temperature of 22 degrees C or 28 degrees C. A rise in the proportion of cells bearing macrophage markers (MAC-1, MAC-3 and F4/80) in the spleen and of FcR+ cells in all tissues tested was found in 22 degrees C-exposed nudes with high nonshivering thermogenesis. Numbers of MAC-1+ macrophages and actively phagocytic cells increased also in peritoneal exudates. There was a conspicuous predominance of large macrophages in the exudates and the specific markers decreased in density on their surface. Ia expression declined in all tissues tested with the length of exposure to cold. In the granulocytic series (BP-2+ cells), there was a decrease in the bone marrow and lymph nodes and an increase in the spleen and circulation, which suggested an enhanced mobilization and increased production at extramedullary sites in cold-exposed nude mice. The changes in haired mice were negligible.
Animals↗
Development of the cellular response in the mouse omentum after intraperitoneal immunization.
Using computer image analysis we studied the development of dense cellular and dense lymphoid areas ("milky spots") and of pendant lymphatic nodules in mouse omenta after intraperitoneal immunization with sheep red blood cells. In both euthymic (BALB/c and hairless BFU) and athymic hairless nu/nu BALB/c mice the proportion of newly developing activated omental areas (AOA) was biphasic, with distinct peaks on days 3-4 and 8-12 after immunization, and a trough on days 5 and 14. There was a small difference between athymic and euthymic BALB/c mice. In comparison with the nu/nu BALB/c mouse, the BFU mutant had a lower proportion of AOA on days 4 and 10. The athymic state is not thought to have a great influence on the AOA development; this depends on a basic macrophage defence, which is well developed in the athymic model, and is self-regulated and shaped by a sequence of cell immigration, settling, differentiation and emigration.
Animals↗
Effect of ambient temperature on immune functions of athymic nude mice.
We performed cytoflourometric analysis of the expression of various T and B surface markers on lymphocytes isolated from bone marrow, spleen and lymph nodes of nu/nu and +/+ mice kept at 22 or 28 degrees C for various time intervals. In bone marrow of nu/nu mice the cold exposure decreased the expression of sIg and CD4 molecules and increased expression of MHC class II antigens. In the spleen, the numbers of MHC class II and sIg expressing lymphocytes continually decreased with the length of cold exposure. At the same time, the number of CD4+ cells increased. The most pronounced changes in lymph nodes were observed in the expression of CD5 antigen. The values obtained from euthymic mice kept at cold temperature were always comparable to those found in mice kept at 28 degrees C. Exposure to lowered temperature caused in nu/nu mice also significant changes in appearance of subpopulations of cells differing in size and in density of antigens. The changes did not affect the antibody response to a thymus-independent antigen.
Animals↗
The effect of an antigenic stimulation on proliferative response in athymic mice.
The proliferation activity of the main cellular categories of bone marrow after infusion of 3H-thymidine was studied in nu/nu and +/+ 1-month- and 3-month-old BALB/c mice in comparison with lymphoid cells in the spleen and mesenteric lymph nodes. The stem cell defect in nu/nu mouse bone marrow is compensated by an increased proliferation in myeloid series and in agranulocytes. The increase of proliferation activity among lymphoid cells in peripheral lymphoid organs was observed only in the 3-month-old mice with a delay in the nudes.
Animals↗
An electron microscopic study of the development of the thymus anlage of athymic (nu/nu) mice.
Using electron microscopy, we examined the anlage of dysgenetic embryo thymuses of nu/nu mice aged 14.5-15 days, 16 days and 18 days p.c., with thymus anlage of nu/+ mice serving as controls. On comparing both types, we noted differences at all intervals which increased in a time-related manner. Lymphoid cells were found only very occasionally in dysgenetic thymus anlage up to day 16 p.c. while there were no capillaries at all in any of the stages investigated. In epithelial reticular cells, undemarcated (membrane non limited) spaces of varying size and containing PAS+ material were found in the cytoplasm (glycogen-like particles seen in electron microscopy). Based on our findings, and on general assumptions, we believe that the primary process occurring in the dysgenetic thymus is abnormal epithelial stroma differentiation resulting not only in a lack of lymphoid cells but, also, in a limited or probably absent vascular bed.
Animals↗
Impact of neonatal benzpyrene imprinting on thymocytic dexamethasone binding in ascitic tumor bearing rats.
1. Rats treated with a single dose of benzpyrene when newborn and inoculated with Walker's ascitic tumor cells when 6 weeks old showed 6 and 9 days later an unequivocal increase, whereas 15 and 20 days later an unequivocal decrease, in dexamethasone binding capacity (receptor number) relative to the control, i.e. a reversion of receptor activity in the course of tumor genesis. 2. The reversion of receptor activity showed a parallelism with the increase of tumor mortality over the control. 3. The experimental observations support the conclusion that neonatal exposure to benzpyrene has a depressive effect on general resistance that is reflected (or probably caused?) among others by a decrease in the binding capacity of glucocorticoid receptors.
Animals↗
Thy 1 expression in the brain of nude mice.
The expression and cell distribution of Thy 1 antigen was studied in the brain of both normal and athymic (nude) young adult mice of the BALB/c strain by immunochemistry. In nude animals Thy 1 fluorescence was less intense and less regularly distributed in the molecular layer of the cerebellum and hippocampus. Thy 1 content determined by ELISA was lower by 10-16% in the cerebellum and 20-25% in the olfactory bulbs of nude mice. The total wet weight of the brain was lower by 16% than in control animals; the deficit in body weight ranged from 34-45%. It is supposed that the changes in Thy 1 expression in nude animals are caused mainly by the underdevelopment of late developing brain regions due to thermoregulatory problems and other postnatal strains occurring in the mutants.
Animals↗
Ossification in nude mice. 2. A histological, histochemical and immunohistochemical study.
The autopodia of proximal limbs as well as the proximal growth plates of the tibia of newborn nu/nu including super nu/nu, nu/+ and +/+ mice were studied. No differences in the ossification of proximal limb autopodia (regarding the distribution of alkaline phosphatase, acid phosphatase or glycosaminoglycans) were observed in mice of genotypes studied. On the other hand, a thinner proximal tibial growth plate characterizes one-month-old nu/nu mice, and also the architecture and alkaline phosphatase pattern were altered. The results suggest a postnatal secondary effect of the nu/nu genotype on skeletal development.
Alkaline Phosphatase↗
Hematopoietic stem cells in +/+, nu/+, and nu/nu C57Bl/10 mice.
Mice with the nu mutation have been shown to have a reduced incidence of spleen colony-forming units (CFU-S), with a higher variability between individual mice compared to +/+ mice. The presence of these defects also in nu/+ mice indicates that this mutation is a codominant trait and that the hematopoietic changes may not be solely caused by thymus dysgenesis. The proportion of CFU-S synthesizing DNA (approximately 40%) has not been significantly different between +/+, nu/+, and nu/nu mice.
Animals↗