Complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) cooperate in the binding of hydrolyzed complement factor 3 (C3i) to human B lymphocytes

The C3b-binding receptor, CR1/CD35, supports CR2/CD21-mediated activation of complement by human B lymphocytes, possibly by associating with CR2 to promote or stabilize the binding of hydrolyzed C3 (C3i), the primary component of the AP convertase, C3i-Bb. To evaluate this hypothesis, we examined the uptake kinetics and binding equilibria for C3i dimer interaction with human blood cells in the absence and presence of CR1- and CR2-blocking mAb. C3i displayed dual uptake kinetics to B lymphocytes, comprising of rapid binding to CR1 and slower binding to CR2. The forward rate constants (k(1)) for CR1 and CR2, operating independently, differed ca. 9-fold (k(1)=193+/-9.4 and 22.2+/-6.0 x 10(3) M(-1)s(-1), respectively). Equilibrium binding of C3i to B lymphocytes was also complex, varying in strength by ca. 13-fold over the C3i concentration range examined. The maximum association constant (K(a, max)=109+/-27.2 x 10(7) l/mole) was ca. 9- and 6-fold greater, respectively, than those for CR1 or CR2 acting alone (K(a)=13.2+/-5.3 and 18.5+/-3.5 x 10(7) l/mole). The high avidity of the CR1-CR2 complex for C3i is consistent with its rates of C3i uptake and release being determined by CR1 and CR2, respectively.     

Serum protein concentration and oncotic pressure relationship in the rat

Summary A formula relating oncotic pressure torat serum protein concentration was derived and found to be in complete agreement with the Landis-Pappenheimer formula derived from measurements onhuman plasma.This study was supported by the Danish Medical Research Council and Johan and Hanne Weimann's legacy.     

Evolution of resource competition between mutually dependent digital organisms

We study the emergence and dynamics of competing strains of digital organisms in a world with two depletable resources. Consumption of one resource produces the other resource as a by-product, and vice versa. As a consequence, two types of mutually dependent organisms emerge that each prey on the waste product of the other. In the absence of mutations, that is, in a purely ecological setting, the abundances of the two types of organisms display a wide range of different types of oscillations, from regular oscillations with large amplitude to irregular oscillations with amplitudes ranging from small to large. In this regime, time-averaged abundance levels seem to be controlled by the relative fitness of the organisms in the absence of resources. Under mutational pressure, on the other hand, populations evolve that seem to avoid the oscillations of intermediate to large amplitudes. In this case, the relative fitness of the organisms in the presence of resources plays an important role in the time-averaged abundance levels as well.     

Mizolastine provides effective symptom relief in patients suffering from perennial allergic rhinitis: a double-blind, placebo-controlled study versus loratadine.

BACKGROUND: Mizolastine is a nonsedating H1 histamine receptor antagonist with additional antiallergic properties currently marketed in Europe for the treatment of seasonal and perennial allergic rhinitis (PAR) and urticaria. OBJECTIVE: This multicenter, randomized, double-blind, parallel-group study was conducted to evaluate the efficacy and safety of mizolastine in PAR compared with loratadine and placebo. METHODS: After a 1-week placebo run-in period, 428 adult PAR patients received placebo (146 of 428), mizolastine 10 mg (141 of 428), or loratadine 10 mg (141 of 428) once daily for 28 days. Symptoms were evaluated by patients and physicians using a total nasal score, evaluating itching, rhinorrhea, nasal blockade, and sneezing severity. RESULTS: Mizolastine treatment resulted in a significantly greater decrease in patient-rated total nasal score than placebo after 2 weeks (D14; -42%, P < 0.001) and at the end of the treatment period (-46%, P = 0.01), and significantly greater than that observed with loratadine at D14 (P = 0.031). No significant difference in change in total nasal score was observed between loratadine and placebo at 2- and 4-week visits. The global safety was satisfactory and the incidence of adverse events was similar in the three treatment groups. CONCLUSIONS: Mizolastine provides effective symptom relief in PAR together with a satisfactory safety profile. Improvement with mizolastine was significantly greater than placebo throughout the study despite a large placebo effect. Also mizolastine's effects were greater those observed with loratadine after 2 weeks of treatment.     

The phosphatidylinositol 3-kinase/protein kinase B signaling pathway is activated by lipoteichoic acid and plays a role in Kupffer cell production of interleukin-6 (IL-6) and IL-10

Sepsis caused by gram-positive bacteria lacking lipopolysaccharide (LPS) has become a major and increasing cause of mortality in intensive-care units. We have recently demonstrated that the gram-positive-specific bacterial cell wall component lipoteichoic acid (LTA) stimulates the release of the proinflammatory cytokines in Kupffer cells in culture. In the present study, we have started to assess the signal transduction events by which LTA induces the production of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and the anti-inflammatory cytokine IL-10 in rat Kupffer cells. LTA was found to trigger phosphorylation of mitogen-activated protein kinases (MAPK) (p38 MAPK and ERK 1/2) and protein kinase B (PKB). Compared to LPS, LTA was more potent in inducing PKB phosphorylation after 40 min, although we found that the cytokine responses were similar. For both bacterial molecules, blocking phosphatidylinositol 3-kinase (PI3-K; Ly294002) or Janus kinase 2 (JAK-2; AG490) particularly affected the induction of IL-6 and IL-10 release, whereas TNF-alpha levels were strongly reduced by inhibition of Src family tyrosine kinases (PP2). All three cytokines were reduced by inhibition of p38 MAPK (SB202190) or the broad-range tyrosine kinase inhibitor genistein, whereas IL-6 release was particularly blocked by inhibition of ERK 1/2 (PD98059). Divergences in the regulatory pathways controlling TNF-alpha, IL-10, and IL-6 production in Kupffer cells following LPS or LTA stimulation may create a basis for understanding how the balance between pro- and anti-inflammatory cytokines is regulated in the liver following infections by gram-positive or gram-negative bacteria.     

Synthesis and properties of molecularly uniform oligourethanes with chain-folding units in the center

The study of a series of molecularly uniform poly(N-alkylurethanes) with a systematically varied and tailored chain architecture has shown that the packing and superstructure can be controlled by the primary structure of the urethane chain and reversibly altered by the sample treatment, respectively. Depending on the conformation or the stereogeometry of the constitutive unit built in the middle of the otherwise symmetrical oligourethane, chain-extended and/or chain-folded crystallization of the urethane chain can occur. The packing order, i. e., adjacent recentry chain-folding or chain-extended crystallization, and the thermal properties of the oligourethanes are related to the chemical structure of the central constitutive unit.     

Spontaneous reanastomosis between lymphatic vessels following syngeneic transplantation of the small intestine in the rat

Abstract Spontaneous lymphvascular reanastomosis (SLR) following small bowel transplantation in rats is of clinical relevance for the resorption of long chain fatty acids. Detailed morphological and molecular data concerning the process of lymphvascular reanastomosis are not available in the literature. In this study SLR was investigated using microradiology and scanning electron microscopy. Between the 8^th and 21^st postoperative days following transplantation SLR does not occur between the intestinal trunk of the transplant and the thoracic duct of the recipient. Instead, an indirect connection was observed between the inserted advential lymphatic vessels of the mesenteric artery and lymphatic vessels of the aorta or ductus deferens, which are connected with the thoracic duct.