Activation of complement by trypanosomes

Summary Factors exhibiting anti-complementary activity released from trypanosomes after incubation at 20°C were described. The active material was shown to consume the first component of bovine complement. While the anticomplementary factor(s) from T. lewisi could activate bovine, human and guinea pig complement, the factor(s) from T. congolense was observed to activate bovine complement, but not guinea pig and only slightly human complement. The roles of complement activating factor(s) of trypanosomes in the pathology of the disease are discussed.This project is supported by National Research Council of Canada grant A 0068 and a grant from the International Development Research Centre.     

Degradation by phytohemagglutinin of the antiviral state induced by interferon]

Phytohaemagglutinin (PHA M and P forms), when added to L 929 cells previously treated by murine interferon, degrades the antiviral state and restores virus sensitivity in the cells. This degradation depends on the amount of the lectin, the contact period with the cell and the presence of PHA membrane receptors. The importance of membrane configuration not only in the induction but also in the maintenance of the antiviral state is discussed.     

ACTH response induced by interleukin-1 is mediated by CRF secretion stimulated by hypothalamic PGE

We investigated whether hypothalamic prostaglandin E2 (PGE2) and corticotropin releasing factor (CRF) are responsible for the development of the adrenocorticotropic hormone (ACTH) response induced by interleukin-1 alpha (IL-1 alpha). The present results show that ACTH responses induced by intravenous injection of IL-1 alpha were suppressed by systemic pretreatment with indomethacin and that intrahypothalamic injection of PGE2 stimulates the secretion of ACTH. Furthermore, systemic pretreatment with anti-CRF antibody significantly suppressed the ACTH response induced by intrahypothalamic injection of PGE2. These data suggest that the ACTH response induced by IL-1 is mediated by CRF secretion stimulated by hypothalamic PGE2.     

Reductive dechlorination of chlorobiphenylols by rats

Summary Dechlorinated products were isolated from the urine of rats that were administered chlorobiphenylols, the primary hydroxylated metabolites of PCB in mammals. The mechanism of chlorine loss from chlorobiphenylols is different from the mechanism of dechlorination via arene oxides whereby concomitant hydroxylation is always observed.A fellowship to the first author by the Organisation for the Advancement of Pure Research (stichting Z. W. O., The Netherlands) is gratefully acknowledged.     

Forecasting volatility by means of threshold models

The aim of this paper is to compare the forecasting performance of competing threshold models, in order to capture the asymmetric effect in the volatility. We focus on examining the relative out‐of‐sample forecasting ability of the SETAR‐Threshold GARCH (SETAR‐TGARCH) and the SETAR‐Threshold Stochastic Volatility (SETAR‐THSV) models compared to the GARCH model and Stochastic Volatility (SV) model. However, the main problem in evaluating the predictive ability of volatility models is that the ‘true’ underlying volatility process is not observable and thus a proxy must be defined for the unobservable volatility. For the class of nonlinear state space models (SETAR‐THSV and SV), a modified version of the SIR algorithm has been used to estimate the unknown parameters. The forecasting performance of competing models has been compared for two return time series: IBEX 35 and S&P 500. We explore whether the increase in the complexity of the model implies that its forecasting ability improves. Copyright © 2007 John Wiley & Sons, Ltd.     

Enhanced depressor reflex by stimulation of superior cervical ganglion and by propranolol

Summary The systemic depressor reflex in cats evoked by inflation of an intrasinusal balloon is enhanced by stimulation of the superior cervical ganglion and by close infusion of 20g/ml/min of (d, 1) propranolol.This work was supported by grant No. 22600-1 NIH, Heart, Lung and Blood Institute, Bethesda, MD.     

Solubilization of unconjugated bilirubin by bile salts

Summary Freshly precipitated uncojugated bilirubin (UCB) is solubilized rapidly and to a large extent by the sodium salts of di- and trihydroxy bile acids. The solubilization effect depending on bile salt concentration, pH and ionic strength is based on micellar mechanisms.     

Hydrolysis of histones by horse urinary kallikreins

Summary Horse urinary kallikrein was shown to hydrolyze histones from calf thymus and chicken nuclei erythrocytes. The hydrolysis is inhibited by benzamidine and hyposulfite but not by soy-bean trypsin inhibitor; horse plasma kallikrein also produces this hydrolysis.Work supported by grants from Projeto BIOQ/FAPESP (São Paulo), FINEP (Rio) and CNPq (Rio).Fellow from CNPq, from Instituto Biológico (São Paulo).     

Modulation by flavonoids of cell multidrug resistance mediated by P-glycoprotein and related ABC transporters

Cancer cell resistance to chemotherapy is often mediated by overexpression of P-glycoprotein, a plasma membrane ABC (ATP-binding cassette) transporter which extrudes cytotoxic drugs at the expense of ATP hydrolysis. P-glycoprotein (ABCB1, according to the human gene nomenclature committee) consists of two homologous halves each containing a transmembrane domain (TMD) involved in drug binding and efflux, and a cytosolic nucleotide-binding domain (NBD) involved in ATP binding and hydrolysis, with an overall (TMD-NBD)2 domain topology. Homologous ABC multidrug transporters, from the same ABCB family, are found in many species such as Plasmodiumfalciparum and Leishmania spp. protozoa, where they induce resistance to antiparasitic drugs. In yeasts, some ABC transporters involved in resistance to fungicides, such as Saccharomyces cerevisiae Pdr5p and Snq2p, display a different (NBD-TMD)2 domain topology and are classified in another family, ABCG. Much effort has been spent to modulate multidrug resistance in the different species by using specific inhibitors, but generally with little success due to additional cellular targets and/or extrusion of the potential inhibitors. This review shows that due to similarities in function and maybe in three-dimensional organization of the different transporters, common potential modulators have been found. An in vitro 'rational screening' was performed among the large flavonoid family using a four-step procedure: (i) direct binding to purified recombinant cytosolic NBD and/or full-length transporter, (ii) inhibition of ATP hydrolysis and energy-dependent drug interaction with transporter-enriched membranes, (iii) inhibition of cell transporter activity monitored by flow cytometry and (iv) chemosensitization of cell growth. The results indicate that prenylated flavonoids bind with high affinity, and strongly inhibit drug interaction and nucleotide hydrolysis. As such, they constitute promising potential modulators of multidrug resistance.     

Inhibition of uridinediphosphate glucuronyltransferase caused by furosemide

Summary The diuretic agent, furosemide, inhibits liver microsomal uridinediphosphate glucuronyltransferase (EC. 2.4.1.17), in monkey and rat. Inhibition is of the non-competitive type.     

Inhibition of uridinediphosphate glucuronyltransferase caused by furosemide

The diuretic agent, furosemide, inhibits liver microsomal uridinediphosphate glucuronyltransferase (EC. 2.4.1.17), in monkey and rat. Inhibition is of the non-competitive type.     

ACTH response induced by interleukin-1 is mediated by CRF secretion stimulated by hypothalamic PGE

Summary We investigated whether hypothalamic prostaglandin E₂ (PGE₂) and corticotropin releasing factor (CRF) are responsible for the development of the adrenocorticotropic hormone (ACTH) response induced by interleukin-1 (IL-1). The present results show that ACTH responses induced by intravenous injection of IL-1 were suppressed by systemic pretreatment with indomethacin and that intrahypothalamic injection of PGE₂ stimulates the secretion of ACTH. Furthermore, systemic pretreatment with anti-CRF antibody significantly suppressed the ACTH response induced by intrahypothalamic injection of PGE₂. These data suggest that the ACTH response induced by IL-1 is mediated by CRF secretion stimulated by hypothalamic PGE₂.     

Regulation of Toll-like receptor signaling by NDP52-mediated selective autophagy is normally inactivated by A20

Toll-like receptor (TLR) signaling is linked to autophagy that facilitates elimination of intracellular pathogens. However, it is largely unknown whether autophagy controls TLR signaling. Here, we report that poly(I:C) stimulation induces selective autophagic degradation of the TLR adaptor molecule TRIF and the signaling molecule TRAF6, which is revealed by gene silencing of the ubiquitin-editing enzyme A20. This type of autophagy induced formation of autophagosomes and could be suppressed by an autophagy inhibitor and lysosomal inhibitors. However, this autophagy was not associated with canonical autophagic processes, including involvement of Beclin-1 and conversion of LC3-I to LC3-II. Through screening of TRIF-interacting ‘autophagy receptors’ in human cells, we identified that NDP52 mediated the selective autophagic degradation of TRIF and TRAF6 but not TRAF3. NDP52 was polyubiquitinated by TRAF6 and was involved in aggregation of TRAF6, which may result in the selective degradation. Intriguingly, only under the condition of A20 silencing, NDP52 could effectively suppress poly(I:C)-induced proinflammatory gene expression. Thus, this study clarifies a selective autophagic mechanism mediated by NDP52 that works downstream of TRIF–TRAF6. Furthermore, although A20 is known as a signaling fine-tuner to prevent excess TLR signaling, it paradoxically downregulates the fine-tuning effect of NDP52 on TLR signaling.     

Initiation of germination of Clostridium difficile spores by lysozyme]

The germination rate of spores of C. difficile which is usually lower than 10(-5) is raised to about 5.10(-3) in presence of lysozyme. All spores are initiated by lysozyme when previously treated by sodium thioglycolate. These spores are indeed lysozyme-dependent for germination.     

Inhibition of rat liver transglutaminase by nucleotides

Summary Tissue-type transglutaminase (TGase) was purified from rat liver, and the effects of nucleotides on its activity were examined. The enzyme activity is inhibited by ATP in a concentration-dependent way, with complete inhibition by 3 mM ATP. Partially-purified TGase from human brain was inhibited by ATP in a manner similar to that observed with the rat liver enzyme. This suggests that the inhibition is a common phenomenon for tissue-type TGase in all species and tissues. The inhibition is reversible since full activity is restored by lowering the ATP concentration. CTP has a TGase-inhibitory potency equivalent to that of ATP, whereas GTP and UTP possess about 50% of the inhibitory activity of ATP. ADP inhibits TGase activity to the same extent as ATP, but AMP causes much less inhibition, and there is no inhibition by adenosine or adenine. The inhibition by ATP is insensitive to ionic strength and is non-competitive with the substrate putrescine. Since ATP levels in cells are of mM order, these results suggest that TGase activity is controlled by ATP in vivo.     

Solubilization of unconjugated bilirubin by bile salts.

Freshly precipitated unconjugated bilirubin (UCB) is solubilized rapidly and to a large extent by the sodium salts of di- and trihydroxy bile acids. The solubilization effect depending on bile salt concentration, pH and ionic strength is based on micellar mechanisms.     

The reactivation of human interferons by guanidine thiocyanate

The addition of 1.5 M guanidine thiocyanate (GuSCN) reactivates inactive human leukocyte interferon. The biological activity of inactivated human fibroblast interferon can be only partially recovered with GuSCN if additional (thermal) energy is supplied.