Absence of peripheral clonal deletion and anergy in immune responses of T cell-reconstituted athymic mice

Superantigens induce clonal deletion of reactive T cells in the thymus and clonal deletion and anergy in the periphery of euthymic mice. In this report we have assessed the ability of Staphylococcal enterotoxin B (SEB) to induce peripheral tolerance in nude mice reconstituted with normal, syngeneic T cells. Immunization of reconstituted nude mice with SEB resulted in lethal toxic shock in a large fraction of the animals. Such lethality was never observed in the normal donor mouse strain. Analysis of lymphokine production in response to SEB showed that reconstituted nude mice produced higher levels of interleukin-2 and tumor necrosis factor-α, but lower levels of interleukin-4, than euthymic control mice. Furthermore, SEB was unable to promote either clonal elimination or induction of anergy in the SEB-responsive peripheral T cells, despite the fact that reconstituted nude mice did produce high levels of corticosterone upon treatment with SEB. These results imply a lack of control over immune responses to superantigen in T cell-reconstituted athymic mice.     

Evaluation of the mutagenic and cytotoxic effects of mercurous chloride by the micronuclei technique in golden Syrian hamsters

The aims of this study were to evaluate the mutagenic and cytotoxic activity of mercurous chloride by the micronucleus technique in vivo on the bone marrow of golden Syrian hamsters after a single i.p. drug administration. Forty male golden Syrian hamsters were classified into eight groups: negative control, positive control and six groups treated with different doses of mercurous chloride (1.25, 2.5, 5, 10, 20 and 40 mg/kg). The negative control was injected with physiological saline i.p. and the positive control with cyclophosphamide at a dose of 80 mg/kg i.p. With respect to mutagenic effect, the average number of micronucleated polychromatic erythrocytes (MPE) in hamsters treated with different doses of mercurous chloride was not significant compared with the negative control. With respect to cytotoxic effect, the average polychromatic erythrocyte/red blood cell ratio showed a significant decrease when the doses were higher than the 2.5 mg/kg dose compared with the negative control. In conclusion, this preliminary study shows a cytotoxic effect but not a mutagenic effect of calomel in vivo at one time point (24 h).     

From rafts to crafts: membrane asymmetry in moving cells

Many important biological events, including the leukocyte-mediated immune response, wound repair, axon guidance and developmental patterning, involve persistent cell movement towards a directional signal, a process termed chemotaxis. Establishment of functional and spatial cell polarity is an absolute requirement for this response. We propose that redistribution of specific membrane microdomains, termed rafts, during cell migration is a pivotal step in achieving polarity. On the one hand, partitioning of molecules into rafts might help to localize proteins at the front or the rear of moving cells, and on the other hand, rafts might function as platforms for local activation and coordination of the signaling pathways involved in cell migration.     

The effects of blood osmolality changes on cat carotid body chemoreceptors in vivo

The possibility that carotid chemoreceptors respond to changes in plasma osmolality was investigated in the cat, perfusing the carotid artery with blood made hyper- or hypo-osmotic and recording chemoreceptor activity from carotid nerve fibers. Blood made hyperosmotic with sucrose or NaCl reduced the chemoreceptor discharge, while hypoosmotic blood increased chemoreceptor activity. The minimal osmolality variation necessary to obtain a detectable frequency change was 3–8% of the control. Frequency changes of 30% of the control were obtained with a 20% variation in osmolality. The frequency variations produced by the osmotic changes lasted as long as the infusion was maintained (up to 15 min). In some instances a rebound was observed when iso-osmotic saline was perfused again. A transient change in frequency and a clear rebound were obtained when blood made hyperosmotic with glycerol was perfused. These effects probably reflect a rapid change in intracellular osmolality due to the free passage of glycerol across cellular membranes.The modifications in chemoreceptor activity consecutive to osmolality variations are the opposite of those observed in isolated and superfused carotid bodies. As it is known that osmolality values affect the smooth muscle of the blood vessels, we conclude that our results are mainly produced by changes in carotid body blood flow due to a direct effect of hyper- and hypo-osmotic solutions on vascular muscle tone. Chemoreceptor excitation during a decrease in blood osmolality may contribute reflexly to the increased vascular resistance observed during acute osmolality reductions in man.     

Expression of the proteoglycans versican and mel-CSPG in dysplastic nevi

Nevi with architectural disorder and cytologic atypia of melanocytes (NAD) (also called dysplastic nevi) have been controversial with regard to their relationship with melanoma risk and to their gradation in 3 degrees of atypia. Versican and the melanoma-associated proteoglycan (mel-CSPG) are 2 major proteoglycans expressed by malignant melanoma, and they have a role in the regulation of cell adhesion, migration, and differentiation. We evaluated the differences in versican and mel-CSPG expression in nevi, NAD with several degrees of atypia, and primary malignant melanoma. Immunoreactivity for versican was negative in benign melanocytic nevi, positive in NAD (ranging from weakly to intensely positive), and intensely positive in malignant melanoma. Immunostaining for mel-CSPG was negative in benign melanocytic nevi and mild to moderately positive in NAD and melanoma. Our results suggest that versican expression may be of value for distinguishing NAD from benign melanocytic nevi and for distinguishing severe NAD from mild and moderate NAD.     

Immunoglobulin isotype in the murine response to polysaccharide antigens

Murine antisera specific for the α (1→3) and α (1→6)-linked glucosyl determinants of dextran, as well as for meningococcal polysaccharide group C, have been examined for the distribution of their immunoglobulin classes and subclasses. Whereas the thymus-independent anti-α (1→3) dextran response in BALB/c mice was found to be IgM > IgG₃ > IgA, thus corresponding to previously published work, neither the α (1→6) response in its thymus-dependent or-independent form, nor the response to purified meningococcal polysaccharide, corresponded to this pattern. No preference for any of the IgG subclasses appeared for these antigens when given as thymus-independent carbohydrates. On the other hand, thymus-dependent forms of α (1→6) dextran showed an IgG₁ > IgG₃ > IgG₂ pattern.     

Relative volume of sertoli cells in monkey seminiferous epithelium: A stereological analysis

Techniques of quantitative stereology have been utilized to determine the relative volume occupied by the Sertoli cells and germ cells in two particular stages (I and VII) of the cycle of the seminiferous epithelium. Sertoli cell volume ranged from 24% in stage I of the cycle to 32% in stage VII. Early germ cells occupied 3.4% in stage I (spermatogonia) and 8.7% in stage VII (spermatogonia and preleptotene spermatocytes). Pachytene spermatocytes occupied 15% (stage I) and 24% (stage VII) of the total volume of the seminiferous epithelium. In stage I the two generations of spermatids comprised 58% of the total epithelium by volume, whereas in stage VII, after spermiation, the acrosome phase spermatids occupied 35% of the total seminiferous epithelial volume.     

Histopathological findings in rabbits after experimental acute exposure to the Loxosceles intermedia (brown spider) venom

Loxoscelism, the term used to describe envenomation with brown spiders, is characterized by a dermonecrotic lesion at the bite site. In the present investigation we submitted albino rabbits to an acute experimental envenomation protocol using Loxosceles intermedia (brown spider) venom, with in order to determine the pathogenesic features of the lesion induced by this spider, which is the cause of several accidents throughout the world. Rabbits received intradermal injections of the venom and were monitored over the first 4 h, and then at 12 h and 1, 2 and 5 days after envenomation. Histological specimens from 3 rabbits per time point were collected from euthanized animals and processed for histological examination by light microscopy. Major findings observed during the first 4 h were oedema, haemorrhage, degeneration of blood vessel walls, plasma exudation, thrombosis, neutrophil accumulation in and around blood vessels with an intensive diapedesis, a diffuse collection of inflammatory cells (polymorphonuclear leucocytes) in the dermis, and subcutaneous muscular oedema. Over the following hours and up to 5 days after envenomation the changes progressed to massive neutrophil infiltration (with no other leucocytes) into the dermis and even into subcutaneous muscle tissue, destruction of blood vessels, thrombosis, haemorrhage, myonecrosis, and coagulative necrosis on the 5th day.     

Formation and specification of ventral neuroblasts is controlled by vnd in Drosophila neurogenesis

During Drosophila neural development, neuroblasts delaminate from the neuroectoderm of each hemisegment in a stereotypic orthogonal array of five rows and three columns (ventral, intermediate, and dorsal). Prevailing evidence indicates that the individual neuroblast fate is determined by the domain-specific expression of genes along the dorsoventral and anteroposterior axis. Here, we analyze the role of Vnd, a NK-2 homeodomain protein, expressed initially in the ventral neuroectoderm adjacent to the ventral midline, in the dorsoventral patterning of the neuroectoderm and the neuroblasts. We show that in vnd null mutants most ventral neuroblasts do not form and the few that form do not develop ventral fates, but instead develop intermediate-like fates. Furthermore, we demonstrate that Vnd influences the gene expression patterns in the ventral proneural clusters and neuroectoderm, and that its action in neuroblast formation includes, but is not exclusive to the activation of proneural AS-C genes. Through the use of GAL4/UAS gene-expression system we show that ectopic Vnd expression can promote ventral-like fates in intermediate and dorsal neuroblasts and can suppress certain normal characteristics of the intermediate and dorsal neuroectoderm. Our results are discussed in the context of the current evidence in dorsoventral patterning in the Drosophila neuroectoderm.