Studies on the induction and expression of T-cell-mediated immunity. XIII. Membrane-associated antigens of cytotoxic T lymphocytes involved in cytotoxicity

An xenogeneic rat anti-mouse T-cell serum, designated RAT*, has been shown to block the cytolytic activity of cytotoxic T lymphocytes (CTL) at a postbinding step. RAT* serum or the IgG fraction was extensively absorbed with the target cell, P815, a DBA mastocytoma, and used with or without further absorption to immunoprecipitate specific molecules from radiolabeled membrane extracts of CTL derived from either in vivo-allosensitized mice or from cytotoxic clones maintained in in vitro cultures. Cell surface sialic acid residues were labeled by oxidation with sodium periodate (NaIO4) and reduction with tritiated sodium borohydride ([3H]NaBH4). Alternatively, cell surface proteins were labeled with 125I by lactoperoxidase-catalyzed iodination. Nonidet P-40 (NP-40)-solubilized radiolabeled membranes were then immunoprecipitated with RAT* serum and analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE). Three membrane-associated molecules of 95,000, 140,000 and 180,000 Mr were found by such analysis. The sensitivity of these three molecules to trypsinization and their susceptibility to labeling with [3H]NaBH4 suggested that they are glycoproteins. Moreover, when RAT* serum or the IgG fraction was absorbed with various cell types, its ability to immunoprecipitate the three molecules correlated with its ability to block cytolysis. Adsorption of RAT* serum with CTL, but not with nonimmune thymocytes, significantly reduced the ability of RAT* serum to inhibit cytotoxicity and to immunoprecipitate the 95k, 140k, and 180k molecules. Thus, these findings suggest that one or more of these cell surface molecules of CTL may be involved in the cytolytic process.     

Inhibition of human lymphocyte activation by wheat germ agglutinin: a model for saccharide-specific suppressor factors

The suppressive effect of wheat germ agglutinin (WGA) on lectin-stimulated blastogenesis and immunoglobulin production was studied. Addition of WGA at 10 micrograms/ml inhibited phytohemagglutinin (PHA)-, concanavalin-A (Con-A)-, and pokeweed mitogen (PWM)-induced mitogenic responses by 70-80%. PWM-driven immunoglobulin synthesis was suppressed by 45% with WGA. The inhibitory effects of WGA were not due to cell death or to interference with lectin binding at the cell surface. Inhibition was dependent on the presence of WGA in the cell culture during the first 24 hr of mitogen exposure and was observed in cultures of both monocyte-depleted peripheral blood mononuclear cells as well as T-cell-enriched populations. WGA-induced inhibition of blastogenesis was blocked by the addition of N-acetylglucosamine (GluNAc) which prevents WGA binding to the cell surface. WGA was found to mimic the suppressive effect of a soluble immune suppressor supernatant (SISS) derived from Con-A-activated mononuclear cell cultures. PHA responses were inhibited by 80 and 95% with SISS and WGA, respectively. The inhibition by both WGA and SISS was totally reversed with addition of GluNAc. Furthermore, WGA and SISS demonstrated competition for the same cell surface receptor site. WGA may therefore be useful as an in vitro model of a saccharide-specific, biologically relevant, soluble mediator for the investigation of mechanisms of immunologic suppression.     

Behavior of lactating rats in a dual-chambered maternity cage

Videotape sampling of behavior in a dual-chambered apparatus indicates that the continuous monitoring of the amount of time a mother spends in the cage with its litter can be taken as a valid reflection of maternal behavior. Nursing is the principal behavior of lactating females while in the compartment with their litters; lying still, consummatory behavior, and activity occur with greater frequency in the cage away from the litter. Both the time that mothers spend with their litters and nursing behavior displayed a 24-hr rhythm with crest values occurring during the period of light.     

Binding of the J 1 Adhesion Molecules to Extracellular Matrix Constituents

The J1 glycoproteins can be obtained in multiple forms in the soluble fraction of developing and adult mouse brain tissue. They are recovered as two forms of apparent molecular weights of 160,000 and 180,000 (J1-160) from adult mouse brain and as forms of apparent molecular weights of 200,000 and 220,000 (J1-220) from developing brain. J1-160 and J1-220 share common epitopes but are considered as separate entities, with J1-220 being immunochemically closely related if not identical to tenascin. Based on the observation that J1 immunoreactivity appears on basement membrane and interstitial collagens after denervation of the neuromuscular junction in adult rodents, we became interested in investigating the binding properties of J1 glycoproteins to extracellular matrix constituents in vitro. Both J1-160 and J1-220 bound to collagens type I-VI and IX but not to laminin, fibronectin, bovine serum albumin, or gelatin under hypotonic buffer conditions. Under isotonic buffer conditions, J1-220 bound to all collagen types, whereas J1-160 bound only to collagen types V and VI with values that could be examined by Scatchard analysis. Binding of J1-220 to collagens displayed two binding constants (KD) between 1.5 and 4.4 X 10(-9) and 1.8 and 5.5 X 10(-8) M, respectively, under hypotonic buffer conditions and a single KD of 2.1-8.0 X 10(-8) M under isotonic buffer conditions. Binding of J1-160 to collagens had an apparent KD of 1.9-8.0 X 10(-9) M under hypotonic buffer conditions. Under isotonic buffer conditions, binding constants of J1-160 to collagen types V and VI were approximately 2 X 10(-8) M. Binding of J1-220 to collagen type I could be inhibited by J1-220, J1-160, and collagen type VI but not by fibronectin or gelatin. Conversely, binding of J1-160 was inhibited by J1-220, J1-160, and collagen type VI (in order of decreasing efficacy of competition). J1-160 and J1-220 were retained on a heparin-agarose column and eluted in a salt gradient at approximately 0.5 M NaCl. The formation of the J1-heparin complexes was inhibited 100-fold more efficiently by heparin than by chondroitin sulfate. These experiments show that J1 glycoproteins resemble in many respects the extracellular matrix constituents fibronectin, laminin, vitronectin, and von Willebrand factor.     

The degradation of distance discrimination in big brown bats (Eptesicus fuscus) caused by different interference signals

The ability of two big brown bats (Eptesicus fuscus) to discriminate the distance to an electronically synthesized phantom target by echolocation was tested in the presence of interfering signals presented slightly before the target echo. Interfering signals were chosen to have differing degrees of similarity to the typical echolocation emission used by the bat in this task (which was the signal used to create the phantom target), and we predicted that the degree of disruption of ranging would be proportional to the similarity of the interference to the target echo. This prediction was not confirmed; rather, all interference signals not identical to the target echo increased the threshold to about twice that found with no interference. When the interference was identical to the target echo, the threshold increased to about 4 times that with no interference. When each bat was presented with phantom target echoes appropriate for the other bat, its range discrimination threshold increased about ten fold, and in this case the degree of interference of different signals was related to their similarity to the target echo, not to their similarity to the bat's normal signal. We suggest that Eptesicus may suppress interference by a more sophisticated strategy than simple linear matched filtering.Abbreviations E exemplar signal - M _f foreign model signal - M _r reversed self-model signal - M _s self-model signal - N noise signal - SPL sound pressure level     

Degenerative Joint Disease and enthesopathies in a Bronze Age population from Sindou cave (Senaillac-Lauzes,Lot, France)

The anthropological characteristics of the people who lived during the cultural period of the Late Bronze Age in South West France still remain practically unknown because very few sites have provided skeletal remains which permit of an exhaustive study. The cave of Sindou is, in that sense, one of the scarce exceptions. Although the sample of Sindou cannot be considered as representative of the whole regional population (N=50), we studied the presence and severity of DJD and enthesopathies of microtraumatic origin with the aim of finding some data which contribute to the knowledge of several biological aspects of this human group. From the results of the comparisons of the Sindou remains with two different medieval samples, a great similarity is deduced for these skeletal markers, but the higher frequency and severity of Achilles tendon enthesopathy in Sindou is a probable index of a higher level of physical stress at this specific localisation.     

Ernst Mayr: Biologist-historian

Ernst Mayr's historical writings began in 1935 with his essay Bernard Altum and the territory theory and have continued up through his monumentalGrowth of Biological Thought (1982) and hisOne Long Argument: Charles Darwin and the Genesis of Modern Evolutionary Thought (1991). Sweeping in their scope, forceful in their interpretation, enlisted on behalf of the clarification of modern concepts and of a broad view of biology, these writings provide both insights and challenges for the historian of biology. Mayr's general intellectual formation was guided by the GermanBildung ideal, with its emphasis on synthetic and comprehensive knowledge. His understanding of how to write history was inspired further by the example of the historian of ideas Arthur Lovejoy. Some strengths and limitations of this approach are explored here through attention to Mayr's treatment of the French biologist J.-B. Lamarck. It is contended that Mayr's contributions to the history of biology are not restricted to his own very substantial historical writings but also include his encouragement of other scholars, his development of an invaluable archive of scientific correspondence, and his insistence that historians who write about evolution and related subjects acquire an adequate understanding of the principles of Darwinian biology.This paper was originally delivered at the biennial meeting of the International Society for the History, Philosophy, and Social Studies of Biology, held in Brandeis in July 1993, in the special session organized by John Greene on Ernst Mayr's contributions to systematics, evolutionary theory, and the history and philosophy of biology. The paper is presented here with only slight modifications of the original, oral presentation. As indicated in the text, a full assessment of Mayr's historical work, including situating that work in the context of Mayr's other work and contemporary developments in the history of science, would require a much more extensive study than I have been able to undertake here.