Genetic control of mitogen-induced B-cell hyperproliferation in SM/J mice

Previous studies have shown that B cells from SM/J mice exhibit hyperproliferative responsiveness to several bacterial-derived B-cell mitogens. This hyperresponse trait was found to be under autosomal, polygenic control by non-H-2 genes. We have now estimated the number of genes involved by statistical analysis of the proliferative responses of splenocytes from SM/J and low-responder C57BL/6J strains, and progeny from the (B6 × SM)F₁, F₂ and (F₁ × B6) crosses. The number of loci involved was ascertained using two different statistical approaches. An estimate of two loci was determined using chi-squared statistics. The second approach, based on an additive model in the natural log scale, also pointed to a lower bound of two genes. We conclude that the hyperresponse to B-cell mitogens in SM/J mice is determined by two autosomal genes which are not linked to the H-2 major histocompatibility complex.Abbreviations used in this paper LPS a bacterial lipopolysaccharide - AVIS a mitogenic preparation from Actinomyces viscosus - B6 C57BL/6J mice - ¹²⁵IUdR ¹²⁵Iodo-deoxyuridine     

CHARACTERIZATION OF HUMAN RECOMBINANT INTERLEUKIN 2 BINDING TO HEPARIN AND HEPARAN SULFATE USING AN ELISA APPROACH

We have developed an enzyme-linked immunosorbent assay (ELISA) approach for the study of interactions between cytokines and glycosaminoglycans. This involves, as solid phase, a synthetic heparin–bovine serum albumin (BSA) complex in which the heparin is coupled via its reducing terminus to the protein using sodium cyanoborohydride. We have investigated the sensitivity and specificity of this experimental technique, employing antithrombin (AT III) and fibroblast growth factor 2 (FGF-2) as well-characterized heparin binding proteins. Using this ELISA method, we have established that human recombinant interleukin (IL-2) binds to heparin in a concentration-dependent manner. Soluble heparin competes for the binding of IL-2 to the complex with 50% inhibition at 5 μg/ml. This IC₅₀value provides an estimate of the binding constant of around 0.5 μM. This value is at least two orders of magnitude larger than that for the binding of IL-2 to its dimeric and trimeric cell surface receptors, but similar to that for binding to the IL-2 receptor β polypeptide acting alone. Our ELISA shows that in addition to soluble heparin, fuciodan also competes for IL-2 binding, but chondroitin sulfate and dermatan sulfate are inactive. Of six heparan sulfates tested, only one highly sulfated preparation competed for IL-2. The interaction between IL-2 and heparin-like glycosaminoglycans is likely to be an important mechanism for retaining IL-2 close to its sites of secretion, thus giving rise to localized concentration gradients in the tissues.     

Making Their Way: Four Books on Youth, Culture, and Identity

Peer Power: Preadolescent Culture and Identity. Patricia A. Adler and Peter Adler. New Brunswick, NJ: Rutgers University Press, 1998. 257 pp.
Angels' Town: Chero Ways, Gang Life, and Rhetorics of the Everyday. Ralph Cintron. Boston: Beacon Press, 1997. 264 pp.
Everyday Courage: The Lives and Stories of Urban Teenagers. Niobe Way. New York: New York University Press, 1998. 310 pp.
At Home in the Street: Street Children of Northeast Brazil. Tobias Hecht. New York: Cambridge University Press, 1998. 267 pp.     

Population density-dependent metal tolerance: One possible basis and its ecological implications

A population density-dependent copper (Cu) resistance mechanism in a gram-negative soil bacterium, strain TDCd1, was shown to be inducible and was accompanied by changes in the protein composition of the outer membrane of the cell envelope. Characteristically, following inoculation of TDCd1 into Cu-supplemented growth media, there was a period of growth inhibition during which the number of individuals tolerant to Cu gradually increased, even though microcultural experiments indicated that some cells died during this period. We concluded that the population density dependency of the resistance mechanism resulted from the interactions between the rate of cell death, the time taken for Cu resistance to develop, and the size of the initial population. Therefore, the ability of relatively large populations of microorganisms to grow in metal-supplemented media under laboratory conditions may have little ecological significance for sparse populations in natural environments.     

Development and characerization of cell lines from subhuman primates

Summary Seven epithelial cell lines derived from kidney and 20 fibroblastic cell lines deriving from lung, heart, muscle, kidney, and skin tissue of five rhesus and six African green monkey fetuses have been established and propagated in culture. Four epithelial cell two fibroblastic cell lines resumed cell multiplication after a period of growth decline, and these lines developed cytogenetic changes and growth characteristics of cells capable of unlimited growth in vitro. Sixteen of the fibroblastic lines derived from lung, heart, muscle, or skin were characterized by a finite life consisting of a period of active cell multiplication, followed by growth decline, senescence, and cell death. Fibroblasts derived from lung appeared to have the greatest growth potential in terms of total population doublings, and fibroblastic lines from rhesus monkeys were usually capable of more doublings than similar lines from African green monkeys. All fibroblastic lines were predominantly diploid during active growth from passages 1 to 30, but several lines developed karyological changes preceding or during growth decline and senescence. All lines tested were found sensitive to a number of human viruses. All tests on these cells for microbial agents and for tumorigenicity have been negative, and the have been preserved by freezing without loss of properties. These cell lines may be useful as standardized substrates in studies requiring nonhuman primate cells. The research upon which this publication is based was performed pursuant to Contract No. NIH-69-100 with the Division of Biologics Standards of the National Institutes of Health.     

Anesthesia for prairie dogs

The combination of 20 mg xylazine/kg of body weight and 100-150 mg ketamine/kg of body weight provided satisfactory levels of anesthesia in 63 prairie dogs, and the combination was tolerated well with a mortality rate of 3.2%.     

Current concepts of basement-membrane structure and function

Conclusion In this brief review we have attempted to describe the known components of basement membranes in relation to the morphology and function of these matrices. Further details of the molecular structures and biosynthesis of these components may be found in original papers and in various reviews (Kefalides, 1973; Spiro, 1976; Kefalides et al., 1979; Heathcote & Grant, 1981).Although basement membranes appear to contain essentially similar protein and carbohydrate moieties, the proportions and organization of these may differ and, in the opinion of the authors, the key to an understanding of basement membranes lies in the recognition of this heterogeneity. At present, structural models of basement membrane are far from satisfactory and should be regarded with reservation.     

Effects on glucose homeostasis and insulin secretion of long term activation of the glucose-dependent insulinotropic polypeptide (GIP) receptor by N-AcGIP(LysPAL37) in normal mice

Glucose-dependent insulinotropic polypeptide (GIP) is a key hormone of the enteroinsular axis. The present study was designed to assess the metabolic effects in healthy mice of long term activation of the GIP receptor by N-AcGIP(LysPAL37), a potent long-acting GIP receptor agonist. Daily injection of N-AcGIP(LysPAL37) (25 nmol/kg body weight) for 14 days had no significant effect on food intake, body weight, glycated hemoglobin levels, non-fasting plasma glucose and insulin concentrations compared to saline treated controls. No significant differences in post-prandial plasma glucose and insulin concentrations were observed between the two groups following 15 min feeding. However, after 14 days, the glycemic response to intraperitoneal (i.p.) glucose was significantly improved in the N-AcGIP(LysPAL37) treated mice compared to controls (P < 0.01). In keeping with this, glucose-mediated insulin secretion was significantly enhanced in the N-AcGIP(LysPAL37) treated group (P < 0.05). No changes in insulin sensitivity or pancreatic insulin content of the N-AcGIP(LysPAL37) treated mice were detected. No adverse reactions were noted and the effects of N-AcGIP(LysPAL37) were reversed by 14 days cessation of treatment. These data indicate that long term activation of the GIP receptor by daily treatment with N-AcGIP(LysPAL37) improved glucose tolerance due to enhancement of pancreatic beta cell glucose responsiveness and insulin secretion.