title: Characteristic features of the SERA multigene family in the malaria parasite

text: Serine repeat antigen (SERA) is conserved among species of the genus Plasmodium. Sera genes form a multigene family and are generally tandemly clustered on a single chromosome. Although all Plasmodium species encode multiple sera genes, the number varies between species. Among species, the members share similar sequences and gene organization. SERA possess a central papain-like cysteine protease domain, however, in some members, the active site cysteine residue is substituted with a serine. Recent studies implicate this gene family in a number of aspects in parasite biology and induction of protective immune response. This review summarizes the current understanding on this important gene family in several Plasmodium species. The Plasmodium falciparum (Pf)-sera family, for example, consists of nine gene members. Unlike other multigene families in Plasmodium species, Pf-sera genes do not exhibit antigenic variation. Pf-sera5 nucleotide diversity is also low. Moreover, although Pf-sera5 is highly transcribed during the blood stage of malaria infection, and a large amount is released into the host blood following schizont rupture, in malaria endemic countries the sero-positive rates for Pf-SERA5 are low, likely due to Pf-SERA5 binding of host proteins to avoid immune recognition. As an antigen, the N-terminal 47 kDa domain of Pf-SERA5 is a promising vaccine candidate currently undergoing clinical trials. Pf-SERA5 and Pf-SERA6, as well as P. berghei (Pb)-SERA3, and Pb-SERA5, have been investigated for their roles in parasite egress. Two P. yoelii SERA, which have a serine residue at the protease active center, are implicated in parasite virulence. Overall, these studies provide insight that during the evolution of the Plasmodium parasite, the sera gene family members have increased by gene duplication, and acquired various functions that enable the parasite to survive and successfully maintain infection in the host. [Image: see text]


title: Evaluating the impact of the weather conditions on the influenza propagation

text: BACKGROUND: Predicting the details of how an epidemic evolves is highly valuable as health institutions need to better plan towards limiting the infection propagation effects and optimizing their prediction and response capabilities. Simulation is a cost- and time-effective way of predicting the evolution of the infection as the joint influence of many different factors: interaction patterns, personal characteristics, travel patterns, meteorological conditions, previous vaccination, etc. The work presented in this paper extends EpiGraph, our influenza epidemic simulator, by introducing a meteorological model as a modular component that interacts with the rest of EpiGraph’s modules to refine our previous simulation results. Our goal is to estimate the effects of changes in temperature and relative humidity on the patterns of epidemic influenza based on data provided by the Spanish Influenza Sentinel Surveillance System (SISSS) and the Spanish Meteorological Agency (AEMET). METHODS: Our meteorological model is based on the regression model developed by AB and JS, and it is tuned with influenza surveillance data obtained from SISSS. After pre-processing this data to clean it and reconstruct missing samples, we obtain new values for the reproduction number of each urban region in Spain, every 10 minutes during 2011. We simulate the propagation of the influenza by setting the date of the epidemic onset and the initial influenza-illness rates for each urban region. RESULTS: We show that the simulation results have the same propagation shape as the weekly influenza rates as recorded by SISSS. We perform experiments for a realistic scenario based on actual meteorological data from 2010-2011, and for synthetic values assumed under simplified predicted climate change conditions. Results show that a diminishing relative humidity of 10% produces an increment of about 1.6% in the final infection rate. The effect of temperature changes on the infection spread is also noticeable, with a decrease of 1.1% per extra degree.Conclusions: Using a tool like ours could help predict the shape of developing epidemics and its peaks, and would permit to quickly run scenarios to determine the evolution of the epidemic under different conditions. We make EpiGraph source code and epidemic data publicly available.


title: In vivo voltammetric studies on release mechanisms for cocaine with γ-butyrolactone

text: The effect of cocaine (20 mg/kg SC) on presynaptic mechanisms of release for dopamine (DA) and for serotonin (5-HT) was studied in nucleus accumbens of unrestrained rats (Rattus norvegicus). The studies were done by assaying synaptic concentrations of DA and 5-HT in the presence of the neuronal impulse flow inhibitor, γ-butyrolactone (γ-BL). The results were compared with cocaine effects on accumbens DA and 5-HT in the freely moving rat, without γ-BL treatment. A neurochemical time course profile showed that the cocaine-induced increase in accumbens synaptic concentrations of DA was significantly blocked (p<0.0001) after DA impulse flow was significantly inhibited (p<0.0038) by γ-BL (35.8%). The neurochemical time course profile concurrently showed that the cocaine-induced decrease in accumbens synaptic concentrations of 5-HT was significantly blocked (p<0.0004) after impulse flow was significantly inhibited (p<0.025) by γ-BL (50.6%). The findings show that cocaine's effects on synaptic concentrations for DA and for HT in accumbens are dependent on neuronal impulse flow. The findings indicate that presynaptic releasing mechanisms, which may be different for DA vis-à-vis 5-HT, play a role in the mechanism of action of cocaine.


title: Chapter 18 Expression of nitric oxide synthase-2 in glia associated with CNS pathology

text: This chapter discusses the expression of nitric oxide synthase-2 (NOS-2) in glia associated with central nervous system (CNS) pathology. The production of nitric oxide (NO) in the nervous system is catalyzed by three, highly homologous isoforms of NO synthase (NOS). NOS-2, the dimeric, heme-containing, soluble protein whose activity is independent of a rise in intracellular calcium, is variously termed ‘inducible,’ ‘immunologic,’ and ‘macrophage NOS (macNOS).’ Nitric oxide inhibits not only NOS-2 activity but also regulates the level of NOS-2 messenger RNA (mRNA) expression through a mechanism involving NF-(K) B. There is specific evidence for the glial expression of NOS-2 associated with neuronal injury and infection of the CNS and in neurodegenerative and demyelinating diseases. Direct injury in the CNS results in a reactive gliosis, characterized by the induction of the glial fibrillary acidic protein gene and changes in astrocyte morphology.


Potential therapeutic approach for the hormonal treatment of lacrimal gland dysfunction in Sjögren's syndrome


title: Structural Elements in RNA

text: This chapter describes the RNA structural characteristics that have emerged so far. Folded RNA molecules are stabilized by a variety of interactions, the most prevalent of which are stacking and hydrogen bonding between bases. Many interactions among backbone atoms also occur in the structure of tRNA, although they are often ignored when considering RNA structure because they are not as well-characterized as interactions among bases. Backbone interactions include hydrogen bonding and the stacking of sugar or phosphate groups with bases or with other sugar and phosphate groups. The interactions found in a three-dimensional RNA structure can be divided into two categories: secondary interactions and tertiary interactions. This division is useful for several reasons. Secondary structures are routinely determined by a combination of techniques discussed in chapter, whereas tertiary interactions are more difficult to determine. Computer algorithms that generate RNA structures can search completely through possible secondary structures, but the inclusion of tertiary interactions makes a complete search of possible structures impractical for RNA molecules even as small as tRNA. The division of RNA structure into building blocks consisting of secondary or tertiary interactions makes it easier to describe RNA structures. In those cases in which RNA studies are incomplete, the studies of DNA are described with the rationalization that RNA structures may be analogous to DNA structures, or that the techniques used to study DNA could be applied to the analogous RNA structures. The chapter focuses on the aspects of RNA structure that affect the three-dimensional shape of RNA and that affect its ability to interact with other molecules.


title: Sialic Acids in Molecular and Cellular Interactions

text: Sialic acids (Sias) are terminal components of many glycoproteins and glycolipids especially of higher animals. In this exposed position they contribute significantly to the structural properties of these molecules, both in solution and on cell surfaces. Therefore, it is not surprising that Sias are important regulators of cellular and molecular interactions, in which they play a dual role. They can either mask recognition sites or serve as recognition determinants. Whereas the role of Sias in masking and in binding of pathogens to host cells has been documented over many years, their role in nonpathological cellular interaction has only been shown recently. The aim of this chapter is to summarize our knowledge about Sias in masking, for example, galactose residues, and to review the progress made during the past few years with respect to Sias as recognition determinants in the adhesion of pathogenic viruses, bacteria, and protozoa, and particularly as binding sites for endogenous cellular interaction molecules. Finally, perspectives for future research on these topics are discussed.


title: The Confined Function Model of the Golgi Complex: Center for Ordered Processing of Biosynthetic Products of the Rough Endoplasmic Reticulum

text: The organized and characteristic elements of the Golgi complex (GC) are the stacked smooth-surfaced cisternae, which are found in the centrosphere of all eukaryotic cells. These cisternae, in conjunction with other associated smooth-surfaced membranes, are responsible for executing net unidirectional intracellular transport (ICT) from the rough endoplasmic reticulum (RER) toward more distally located structures. This chapter focuses on the broad range of accessory activities that occur during transport, the family of “posttranslational modifications.” These events are, in all likelihood, not essential for the “primary” function of the GC yet they are crucial in allowing the cell to tailor its biosynthetic products for its own needs and the needs of the organism as a whole. In addition to modifying products of the rough endoplasmic reticulum, the GC may be involved in processing events because of its participation in other routes of vesicular traffic—for example, centripetal traffic from the cell surface. Various nonequivalent criteria have been used to ascribe processing events to the GC-autoradiography, preparative or analytic subcellular fractionation, interruption by ICT inhibitors, and delay in the impact of cycloheximide.


title: Chemical and Computer Probing of RNA Structure

text: Ribonucleic acids (RNAs) are one of the most important types of biopolymers. RNAs play key roles in the storage and multiplication of genetic information. They are important in catalysis and RNA splicing and are the most important steps of translation. This chapter describes experimental methods for probing RNA structure and theoretical methods allowing the prediction of thermodynamically favorable RNA folding. These methods are complementary and together they provide a powerful approach to determine the structure of RNAs. The three-dimensional (tertiary) structure of RNA is formed by hydrogen-bonding among functional groups of nucleosides in different regions of the molecule, by coordination of polyvalent cations, and by stacking between the double-stranded regions present in the RNA. The tertiary structures of only some small RNAs have been determined by high-resolution X-ray crystallographic analysis and nuclear magnetic resonance analysis. The most widely used approach for the investigation of RNA structure is chemical and enzymatic probing, in combination with theoretical methods and phylogenetic studies allowing the prediction of variants of RNA folding. Investigations of RNA structures with different enzymatic and chemical probes can provide detailed data allowing the identification of double-stranded regions of the molecules and nucleotides involved in tertiary interactions.


title: Distinguishing effects of cocaine IV and SC on mesoaccumbens dopamine and serotonin release with chloral hydrate anesthesia

text: The effect of IV cocaine (0.5 and 1.0 mg/kg) was studied on synaptic concentrations of dopamine (DA) and serotonin [5-hydroxytryptamine (5-HT)] in the mesoaccumbens nerve terminal, the nucleus accumbens (NAcc), in chloral hydrate-anesthetized, male Sprague-Dawley rats (Rattus norvegicus) with in vivo electrochemistry (voltammetry). In further in vivo voltammetric studies, the effects of SC cocaine on synaptic concentrations of DA and 5-HT were studied in the chloral hydrate-anesthetized paradigm in two neuroanatomic substrates, NAcc and mesoaccumbens somatodendrites, the ventral tegmental area (VTA-A(10)), in a dose-response fashion (10, 20 and 40 mg/kg) in six separate studies. Moreover, in two additional in vivo voltammetric studies, again using the chloral hydrate-anesthetized paradigm, the impulse flow blocker, γ-butyrolactone (γ-BL) (750 mg/kg, IP), was studied alone and in combination with SC cocaine (20 mg/kg) to determine whether or not cocaine can act by presynaptic releasing mechanisms for DA and 5-HT. The results show that IV cocaine concurrently and significantly increased DA and 5-HT release in the NAcc (p < 0.001, p < 0.0005, respectively) at both doses tested. Moreover, IV cocaine effects on DA and 5-HT release were significantly and positively correlated (p < 0.01). On the other hand, SC cocaine concurrently and significantly decreased DA and 5-HT release in NAcc (p < 0.0001) and VTA (p < 0.0001) at each separate dose tested. SC cocaine effects on DA and 5-HT release were significantly and positively correlated across dose and neuroanatomic substrate (p < 0.01). Furthermore, the γ-BL studies indicate that cocaine's action includes a presynaptic release mechanism for the biogenic amines. Summarily, the data show that a consideration of the route of cocaine administration is crucial in determining the underlying neurochemical basis for cocaine.


Sequential morphology of graft-versus-host disease in the rat radiation chimera()


title: 8 The Development of the Kidney

text: This chapter describes the earlier stages of development of the vertebrate metanephric kidney. It focuses on the mouse and descriptive morphology is used for considering both molecular mechanisms, underpinning kidney morphogenesis and differentiation, and the ways in which these processes can go awry and lead to congenital kidney disorders—particularly in humans. The mature kidney is a fairly complex organ attached to an arterial input vessel and two output vessels, the vein and the ureter. Inside, the artery and vein are connected by a complex network of capillaries that invade a large number of glomeruli, the proximal entrance to nephrons, which are filtration units that link to an arborized collecting-duct system that drains into the ureter. The ability of the kidney and isolated metanephrogenic mesenchyme, to develop in culture means that the developing tissues can be subjected to a wide variety of experimental procedures designed to investigate their molecular and cellular properties and to test hypotheses about developmental mechanisms.


title: Functions of alphavirus nonstructural proteins in RNA replication

text: Alphaviruses are enveloped positive-strand RNA viruses transmitted to vertebrate hosts by mosquitoes. Several alphaviruses are pathogenic to humans or domestic animals, causing serious central nervous system infections or milder infections, for example, arthritis, rash, and fever. The structure and replication of Semliki Forest virus (SFV) and Sindbis virus (SIN) have been studied extensively during the past 30 years. Alphaviruses have been important probes in cell biology to study the translation, glycosylation, folding, and transport of membrane glycoproteins, as well as endocytosis and membrane fusion mechanisms. A new organelle, the intermediate compartment, operating between the endoplasmic retieulum and the Golgi complex has been found by the aid of SFV. During the past 10 years, alphavirus replicons have been increasingly used as expression vectors for basic research, for the generation of vaccines, and for the production of recombinant proteins in industrial scale. The main approaches of laboratories in the recent years have been twofold. On one hand, they have discovered and characterized the enzymatic activities of the individual replicase proteins and on the other hand, they have studied the localization, membrane association, and other cell biological aspects of the replication complex.


Erosion of physician autonomy and public respect for the profession()


title: The Role of the 5′ Untranslated Region of Eukaryotic Messenger RNAs in Translation and Its Investigation Using Antisense Technologies

text: This chapter discusses the recent advances in the field of translational control and the possibility of applying the powerful antisense technology to investigate some of the unanswered questions, especially those pertaining to the role of the 5’untranslated region (UTR) on translation initiation. Translational regulation is predominantly exerted during the initiation phase that is considered to be the rate-limiting step. Two types of translational regulation can be distinguished: global, in which the initiation rate of (nearly) all cellular messenger RNA (mRNA) is controlled and selective, in which the translation rate of specific mRNAs varies in response to the biological stimuli. In most cases of global regulation, control is exerted via the phosphorylation state of certain initiation factors, whereas only a few examples of selective regulation have been characterized well enough to define the underlying molecular events. Interestingly, cis-acting regulatory sequences, affecting translation initiation, have been found not only in the 5’UTRs of selectively regulated mRNAs, but also in the 3’UTRs. Thus, in addition to the protein encoding open reading frames, both the 5’ and 3’UTRs of mRNAs must be considered for their effect on translation.


title: Subacute Sclerosing Panencephalitis: Are Antigenic Changes Involved in Measles Virus Persistence?

text: Subacute sclerosing panencephalitis (SSPE) is a rare, fatal complication of measles virus infection arising years after acute measles. During this chronic disease process, characteristic measles virus inclusions are present in the cells of the central nervous system (CNS). During SSPE, infectious virus is not present either in the CNS or other tissues, but it has proved possible, in some cases, to rescue a measles-like virus by cocultivation techniques. These viruses may differ from measles virus, and from each other, but no single, stable property differentiates them. Differences between various strains of measles virus are of a similar magnitude to those observed between SSPE and measles viruses. This chapter discusses experiments to differentiate these agents using monoclonal antibodies raised against purified measles virus Edmonston. In no case is an isolate of measles virus available from the acute phase of infection preceding the develoment of SSPE by the same patient. This event is modeled in vitro by using a tissue culture of Vero cells persistently infected with an SSPE virus “Lec,” and this system is compared to other carrier cultures. These in vitro persistent infections differ from any in vivo persistence, because they are maintained in the absence of an immune response and may provide an insight into the importance of that phenomenon in the development of SSPE.


[1] Purification of viral polymerases: General considerations


title: Cocaine: On-line analysis of an accumbens amine neural basis for psychomotor behavior

text: Dose-response studies on subcutaneous cocaine were done to ascertain its effects in nucleus accumbens in dopaminergic and serotonergic neuronal circuitry in the behaving rat with in vivo voltammetry. Simultaneously, and at each dose of cocaine, unconditioned psychomotor stimulant behavior induced by cocaine was studied in terms of multiple concurrent measures of spontaneous behavior and by activity patterns of locomotion. Time course studies showed that the neurochemical effects of cocaine (10, 20, and 40 mg/kg SC) significantly (p<0.001) increased accumbens synaptic concentrations of dopamine (DA) and concurrently and significantly (p<0.0001) decreased accumbens synaptic concentrations of serotonin (5-HT) in a dose response manner. Simulataneous behavioral time course studies showed that cocaine (10, 20, and 40 mg/kg SC) significantly (p<0.0001) increased ambulations (locomotor activity), fine movements (stereotypic movements of sniffing and grooming) and rearing behavior, while significantly decreasing agoraphobic behavior, as measured by a statistically significant increase in central ambulations (p<0.0001). The high dose of cocaine (40 mg/kg SC) significantly increased fine movements over those produced by the lower doses of cocaine (p<0.0002). One import of the findings is that the DA and 5-HT biogenic amine response occurs in a behavioral paradigm of psychomotor stimulation, which is a known measure of reinforcement. Another is that the biogenic amines DA and 5-HT are affected by cocaine in this reinforcement paradigm with exactly opposite directionality. Finally, acute cocaine administration is shown to produce a dose response inhibition of agoraphobia (fear),w hich is highly correlated (ϱ=.983, p<0.01) with the opposing effects of cocaine on the accumbens biogenic amines, DA and 5-HT.


title: Viruses and Evolution

text: This chapter discusses the role of viruses in nature. Viral transduction of structural and regulatory genes provides a means for information to leave the body of an organism other than through the germ cells. Natural selection acts upon the cell–virus nucleic acid coupling and the rate and direction of the evolution of any species depends upon the number of associated viruses and the extent to and speed with which they allow information to be cycled through the total gene pool of that population. There are three mechanisms by which gene material can be transferred from cell to cell: (1) transformation, (2) transduction, and (3) sexual conjugation. Transformation is the most random and inefficient process; it requires the laws of diffusion and the existing chemistry of the cell membrane, modified in contemporary cells by the development of transport systems, which facilitate membrane penetration. Transduction requires the development of genes for capsomere proteins to encapsidate nucleic acid and a sophistication of the process of membrane evagination to package nucleic acid into free particles, These are relatively modest genetic adaptations. However, true sexual union as it occurs in modern eukaryotes, requires such a high degree of cytological organization that it is inconceivable that it could have operated efficiently during the first billion or so years of cell evolution.


[5] Characterization of coronavirus RNA polymerase gene products


title: Cocaine's colocalized effects on synaptic serotonin and dopamine in ventral tegmentum in a reinforcement paradigm

text: The effect of subcutaneous (SC) cocaine (20 mg/kg) on synaptic concentrations of the biogenic amines, dopamine (DA), and serotonin (5-HT) in Ventral Tegmental Area, (VTA-[A(10)]) was studied in freely moving and behaving rats (rattus norvegicus) with in vivo voltammetry (in vivo electrochemistry). The actual detection of the biogenic amines was on-line and within a temporal resolution of seconds. Simultaneously, the psychostimulant behavior induced by cocaine was studied by infrared photocell beam detection. The results show that cocaine concurrently and significantly increased synaptic concentrations of DA (p < 0.0001) and 5-HT (p < 0.004) in VTA. Serotonin changes were accompanied by a notable oscillatory pattern. Importantly, DA and 5-HT changes in VTA were significantly and positively correlated (p < 0.01). Moreover, psychostimulant behaviors induced by cocaine were significantly increased over control values (p < 0.0001). Psychostimulant behaviors were significantly correlated with concurrently changing synaptic concentrations of DA (p < 0.01) and also with 5-HT to a lesser degree. Additionally, behavioral data indicate that cocaine may exhibit an anxiolytic effect during acute administration because agoraphobic behavior, as shown by increased central ambulatory behavior, was dramatically reduced by cocaine. Summarily, the present findings show that cocaine increased synaptic concentrations of DA in VTA, an action that is correlated with cocaine-induced psychostimulant behavior. The DA-ergic effect appears to be tonically maintained. Furthermore, new findings demonstrate a colocalized, cocaine induced 5-HT-ergic effect in VTA, which keeps pace with cocaine-induced alterations in DA-ergic neurotransmission. Thus, 5-HT may be a relay or a gating mechanism for a DA reward signalling pathway for cocaine.


title: Real time detection of acute (IP) cocaine-enhanced dopamine and serotonin release in ventrolateral nucleus accumbens of the behaving Norway rat

text: Cocaine (10 mg/kg), administered intraperitoneal (IP), was studied for its effects on dopamine (DA) and serotonin (5-HT) release in ventrolateral nucleus accumbens (vlNAcc) of conscious and behaving male, virus-free, Sprague-Dawley rats with in vivo electrochemistry (voltammetry). Miniature stearate probes detected DA and 5-HT release, on line and within a temporal resolution of seconds. Psychostimulant behaviors, in the form of four behavioral components (i.e., the classically DA-dependent behaviors of locomotor activity [ambulations], rearing, and stereotypy, and a 5-HT-ergic behavior, central ambulations) were studied concurrently with infrared photobeam detection. The results show that (IP) cocaine significantly increased vlNAcc DA release (p < 0.0001) and 5-HT release (p < 0.0012). Each of the four parameters of cocaine-induced psychostimulant behavior was concurrently and significantly increased as well (ambulations: p < 0.0001; rearing: p < 0.0008; stereotypy: p < 0.0004; central ambulations: p < 0.0082). Moreover, exactly coincident data points for DA and 5-HT release occurred 10 and 40 min after (IP) cocaine administration. Cocaine-induced DA and 5-HT release were highly and positively correlated during the first hour of study (p < 0.01). As expected, increased DA release in vlNAcc after cocaine administration was significantly and positively correlated with classically DA-dependent behaviors (first- and second-hour effects) (p < 0.01) and with the 5-HT-ergic behavior, central ambulations (p < 0.01). Also, cocaine-induced 5-HT release was significantly and positively correlated with 5-HT behavior (p < 0.01). However, not as expected, classically DA-dependent behaviors were more positively correlated with cocaine-induced 5-HT release in vlNAcc throughout the two-hour period of study. Thus, the present findings show that 5-HT is a comediator with DA in the cocaine response in vlNAcc. Importantly, 5-HT may signal the known DA response to cocaine.


title: Glycosylation in Intestinal Epithelium

text: This chapter reviews the glycosylation reactions in the intestinal epithelium. The intestinal epithelium represents a good model system in which the glycosylation process can be studied. The intestinal epithelium is composed of two basic epithelial cell types: the absorptive enterocyte and the mucus-producing goblet cell. Gastrointestinal epithelial renewal ensues through the processes of cell proliferation, migration, and differentiation. This renewal occurs in discrete proliferative zones along the gastrointestinal tract. In the small intestine, this proliferative zone is restricted to the base of the crypts, whereas in the large intestine it is less restrictive, occurring in the basal two thirds of the crypt. A longitudinal section along the crypt-to-surface axis, cells in various degrees of differentiation is observed, providing a unique in vivo system in which to investigate differentiation-related glycosylation events. The glycoconjugate repertoire displayed by a given cell reflects its endogenous expression of glycosyltransferases. The role played by terminal oligosaccharide structures in cell–cell recognition phenomena and the expression of glycosyltransferases occupy a key position in the post-translational processing of glycoconjugates and thus influence cellular function.


title: Protease-dependent virus tropism and pathogenicity

text: Viral tissue tropism in a susceptible host is often determined by virus-receptor interactions. Nevertheless, closely related viruses utilizing the same receptor molecules can display striking differences in tropism, or a virus can cause a localized infection despite the widespread occurrence of the receptor. These events are now explained by another mechanism of tropism, in which host proteases play a major role by activating viral fusion glycoproteins.


The role of RNA priming in viral and trypanosomal mRNA synthesis


A paradigm for virus-induced demyelinating disease


title: Épidémiologie des diarrhées aiguës infectieuses en France et en Europe

text: Acute infectious diarrhoea can be linked to various pathogens among which viruses are responsible for more than a half cases. Rotaviruses and caliciviruses are the most frequently encountered, in close to 60 % of viral gastroenterititis. Rotaviruses account for more than 50 % of severe diseases and caliciviruses, especially norovirus are reponsible for less severe sporadic gastroenteritis and water-or food- borne epidemics. Astroviruses and adenoviruses are minority, excepted for immunocompromised patients. Viral or Bacterial and viral co- infections are frequent (up to 15 %). To date, the first rotavirus vaccine assays did not reveal any shift from a viral genus to another, such as calicivirus or adenovirns, according to the fact that epidemiologic features of these viruses are quite different. Progress in viral diagnosis and genotyping enabled to analyse viral diversity and to follow viral recombination events, and emergence of new variants that could propagate among various countries. This dynamic evolution that concerns not only Europe but also developing countries should be carefully surveyed at the era of rotavirus vaccination.


Macromolecular assemblages


title: Mise au point : évolution des indications de la coloscopie chez l’enfant en 2012()

text: Indications for ileocolonoscopy were defined in 2002 by the Groupe Francophone d’Hépatologie Gastroentérologie et Nutrition. These recommendations were updated with new data and technical innovations appearing over the last decade. Ileocolonoscopy is primarily indicated for digestive bleeding or anemia and for suspected inflammatory bowel disease. It is now indicated in inflammatory bowel disease for control of mucosal healing after medical treatment and relapse after surgical resection. Iterative ileocolonoscopy is primarily indicated for genetic polyposis and well defined for familial adenomatous polyposis. The contraindications were not modified.


title: Genetic engineering of animal RNA viruses

text: The ability to genetically manipulate viruses has led to extraordinary advances in understanding virus biology and to the establishment of useful vector systems. Initially confined to DNA viruses and retroviruses, RNA viruses have more recently become attractive candidates for expression of heterologous genes and offer promising perspectives for biomedical applications.


title: Toxicological implications of extended space flights

text: The dominant reason for exposing humans to the risks of space flight is their ability to perform complex tasks and make complex decisions. To fulfill such a role, crews must be shielded against even incipient degradation of performance capacity. The space environment contains potential hazardsranging from microgravity to infectious microorganisms to chemical toxicants. An extensive literature indicates that incipient disruptions of function may occur at low levels of exposure to toxic agents and degrade performance. Such questions need to be pursued before irreversible decisions are made about space vehicle design.


title: Two mRNAs that differ by two nontemplated nucleotides encode the amino coterminal proteins P and V of the paramyxovirus SV5

text: The “P≓ gene of the paramyxovirus SV5 encodes two known proteins, P (M(r) ≈ 44,000) and V (M(r) ≈ 24,000). The complete nucleotide sequence of the “P≓ gene has been obtained and is found to contain two open reading frames, neither of which is large enough to encode the P protein. We have shown that the P and V proteins are translated from two mRNAs that differ by the presence of two nontemplated G residues in the P mRNA. These two additional nucleotides convert the two open reading frames to one of 392 amino acids. The P and V proteins are amino coterminal and have 164 amino acids in common. The unique C terminus of V consists of a cysteine-rich region that resembles a cysteine-rich metal binding domain. An open reading frame that contains this cysteine-rich region exists in all other paramyxovirus “P≓ gene sequences examined, which suggests that it may have important biological significance.


title: Enteric Infectious Disease in Neonates: Epidemiology, Pathogenesis, and a Practical Approach to Evaluation and Therapy

text: There are many bacterial and viral pathogens that have been associated with enteric disease during the newborn period. These pathogens have widely different mechanisms of action on the intestinal epithelium and are associated with a spectrum of clinical findings. Infected infants can be asymptomatic, have gastroenteritis, or have a fulminant sepsis picture. To determine therapy and institute appropriate infection control measures requires the ability to recognize the clinical syndrome and correctly interpret laboratory results. All of these principles can be applied to the premature infant in the neonatal intensive care nursery as well as the full-term infant at home.


What roles do growth factors play in CNS remyelination?


title: Antibody-mediated clearance of viruses from the mammalian central nervous system

text: The novel role of antibody in clearing virus from the central nervous system without the help of other immune effectors is an important phenomenon that has only recently been documented. Possible routes for antibodies across the blood-brain barrier and how they work in the CNS are discussed here.


title: [2] Families of serine peptidases

text: This chapter examines families of serine peptidases. Serine peptidases are found in viruses, bacteria, and eukaryotes. They include exopeptidases, endopeptidases, oligopeptidases, and omega peptidases. On the basis of three-dimensional structures, most of the serine peptidase families can be grouped together into about six clans that may have common ancestors. The structures are known for members of four of the clans, chymotrypsin, subtilisin, carboxypeptidase C, and Escherichia D-Ala-D-Ala peptidase A. The peptidases of chymotrypsin, subtilisin, and carboxypeptidase C clans have a common “catalytic triad” of three amino acids—namely, serine (nucleophile), aspartate (electrophile), and histidine (base). The geometric orientations of these are closely similar between families; however the protein folds are quite different. The arrangements of the catalytic residues in the linear sequences of members of the various families commonly reflect their relationships at the clan level. The members of the chymotrypsin family are almost entirely confined to animals. 10 families are included in chymotrypsin clan (SA), and all the active members of these families are endopeptidases. The order of catalytic residues in the polypeptide chain in clan SA is His/Asp/Ser.


Notes to applicants for marketing authorizations on the production and quality control of monoclonal antibodies of murine origin intended for use in man


Gene expression and differentiation


title: Necrotizing Enterocolitis and Infection

text: Infections are considered to play an important role in the pathogenesis of necrotizing enterocolitis (NEC). The evidence for infectious causes of NEC is reexamined, with special attention to the clinical definition and reported outbreaks of NEC. Future areas of study are proposed.


Severe acute respiratory syndrome (SARS)


Alternative readings of the genetic code


title: Adaptive surface variation in mycoplasmas

text: Mycoplasmas excel as infectious agents, despite their very small genomes. In one mycoplasma species, adaptive flexibility is enhanced by an elegant genetic system that diversifies the membrane surface through a set of variable lipoproteins (Vlps). A family of vlp genes supplies divergent coding sequences and undergoes high-frequency mutations, thus creating large repertoires of surface mosaics and structural variants.


NASAL DISORDERS AND SINUSITIS


Mechanisms of virus replication, persistence, and regulation of immune responses


title: Viral strategies of translation initiation: Ribosomal shunt and reinitiation

text: Due to the compactness of their genomes, viruses are well suited to the study of basic expression mechanisms, including details of transcription, RNA processing, transport, and translation. In fact, most basic principles of these processes were first described in viral systems. Furthermore, viruses seem not to respect basic rules, and cases of “abnormal” expression strategies are quiet common, although such strategies are usually also finally observed in rare cases of cellular gene expression. Concerning translation, viruses most often violate Kozak's original rule that eukaryotic translation starts from a capped monocistronic mRNA and involves linear scanning to find the first suitable start codon. Thus, many viral cases have been described where translation is initiated from noncapped RNA, using an internal ribosome entry site. This review centers on other viral translation strategies, namely shunting and virus-controlled reinitiation as first described in plant pararetroviruses (Caulimoviridae). In shunting, major parts of a complex leader are bypassed and not melted by scanning ribosomes. In the Caulimoviridae, this process is coupled to reinitiation after translation of a small open reading frame; in other cases, it is possibly initiated upon pausing of the scanning ribosome. Most of the Caulimoviridae produce polycistronic mRNAs. Two basic mechanisms are used for their translation. Alternative translation of the downstream open reading frames in the bacilliform Caulimoviridae occurs by a leaky scanning mechanism, and reinitiation of polycistronic translation in many of the icosahedral Caulimoviridae is enabled by the action of a viral transactivator. Both of these processes are discussed here in detail and compared to related processes in other viruses and cells.


Hyperleucocytose au cours des urgences pédiatriques


Chromosomes and expression mechanisms


title: Long-term humoral immunity against viruses: revisiting the issue of plasma cell longevity

text: Despite extensive documentation of prolonged antibody responses following vaccination or acute viral infection, the mechanisms behind long-term antibody production are not fully understood. We propose the hypothesis that long-lived plasma cells are an important, yet largely overlooked, component of long-term humoral immunity.


Risque de méthémoglobinémie après application d'Emla® chez les prématurés


Protein sorting by selective retention in the endoplasmic reticulum and Golgi stack


Oncogenes and cell proliferation


Infection respiratoire nosocomiale par le coronavirus dars une unité de réanimation néonatále: évaluation prospective


Place des infections virales dans la crise d'asthme


title: Problems and prospects of developing effective therapy for common cold viruses

text: No effective treatment for common colds has yet been developed. Combination antiviral and anti-inflammatory therapies are the best hope for intervention after the onset of symptoms. Prophylaxis, especially in the form of vaccination, would have a major impact in disease prevention. These approaches offer new avenues for treating populations at risk and are of particular significance to those with asthma or chronic bronchitis.


Differentiation and gene regulation


title: La légionellose chez l'enfant immunocompétent : À propos d'un cas

text: We report a case of Legionella pneumonia in an immunocompetent child. Legionella pneumonia is a rare pathology among children,and even rarer when they are immuno-competent; a few cases have been reported in the literature. This is explained by the fact that infection occurs primarily to immuno-suppressed patients. Legionella bacteria are not systematicaly sought for in front of child's atypical pneumonia, contrary to Mycoplasma or Chlamydiae. In addition, a number of cases are probably not even noticed because either not serious (Pontiac fever), spontaneously cured, or cured with macrolides prescribed in the case of suspected pneumonia with Mycoplasma.


Un service de soins urgents externes de kinésithérapie respiratoire pédiatrique à l'hôpital


Viral genetics


Communications libres


Antibiothérapie et asthme de l'enfant


title: Targeting of viral glycoproteins to the Golgi complex

text: Certain enveloped viruses are known to assemble on membranes of the Golgi complex. Intracellular budding is facilitated by targeting of the viral glycoproteins to this organelle. It is likely that these viral glycoproteins are retained in the Golgi by the same means as are endogenous Golgi proteins. Consequently, the study of Golgi-specific viral proteins has provided important clues to the nature of Golgi retention signals.


title: RNA viruses: genome structure and evolution

text: The explosive pace of sequencing of RNA viruses is leading to rapid advances in our understanding of the evolution of these viruses and of the ways in which their genomes are organized and expressed. New insights are coming not only from genomic nucleotide sequence comparisons, but also from direct sequencing of transcribed mRNAs and of RNAs that serve as intermediates in replication.


Crystal structure of the Yersinia tyrosine phosphatase


Conclusions reached at the IABS Symposium on Immunity to infections of the respiratory system in man and animals: London 22–25 April, 1974


Vaccination of man and animals by the non-parenteral route: Isle-of-Man, September 1975 Summary and conclusion


Sorting of membrane proteins in the secretory pathway


title: Use of macromolecular assemblies as expression systems for peptides and synthetic vaccines

text: The past decade has witnessed the development of numerous systems for the presentation of antigens on the surface of self-assembling macromolecules. Although the sites for insertion were initially chosen empirically, the determination of the three-dimensional structures of a number of carrier macromolecules has enabled structure-based insertional mutagenesis to be used increasingly. Furthermore, it is now feasible to determine the structure of an inserted sequence as presented in a heterologous environment, making it possible to correlate the detailed structure of a peptide with its immunological properties.


title: Epidemiology of Necrotizing Enterocolitis

text: The descriptive epidemiology of necrotizing enterocolitis (NEC) is presented. Areas addressed include incidence, race, sex, age of onset, mortality rates, and endemic versus epidemic disease. Both descriptive and case control studies are reviewed to uncover clues relevant to the causes, pathogenesis, and prevention of NEC.


title: Year of the genome

text: Small Genomes: Sequencing, Functional Characterization and Comparative Genomics (TIGR Science Education Foundation conference) held at Hilton Head, SC, USA, 25–28 January 1997.


Endogenous retroviruses: are they the cause of multiple sclerosis?


title: Molecular mimicry in T cell-mediated autoimmunity: Viral peptides activate human T cell clones specific for myelin basic protein

text: Structural similarity between viral T cell epitopes and self-peptides could lead to the induction of an autoaggressive T cell response. Based on the structural requirements for both MHC class 11 binding and TCR recognition of an immunodominant myelin basic protein (MBP) peptide, criteria for a data base search were developed in which the degeneracy of amino acid side chains required for MHC class 11 binding and the conservation of those required for T cell activation were considered. A panel of 129 peptides that matched the molecular mimicry motif was tested on seven MBP-specific T cell clones from multiple sclerosis patients. Seven viral and one bacterial peptide efficiently activated three of these clones. Only one peptide could have been identified as a molecular mimic by sequence alignment. The observation that a single T cell receptor can recognize quite distinct but structurally related peptides from multiple pathogens has important implications for understanding the pathogenesis of autoimmunity.


Infections virales et à germes atypiques au cours des crises d'asthme de l'enfant


Bien évaluer l'épidémie à VRS


Infection à coronavirus du nourrison: atteinte des voies aériennes basses, apnée et mort subite?


La maladie de Kawasaki sous toutes ses facettes


title: An alternative approach to characterize the topology of complex networks and its application in epidemic spreading

text: Based on the mean-field approach, epidemic spreading has been well studied. However, the mean-field approach cannot show the detailed contagion process, which is important in the control of epidemic. To fill this gap, we present a novel approach to study how the topological structure of complex network influences the concrete process of epidemic spreading. After transforming the network structure into hierarchical layers, we introduce a set of new parameters, i.e., the average fractions of degree for outgoing, ingoing, and remaining in the same layer, to describe the infection process. We find that this set of parameters are closely related to the degree distribution and the clustering coefficient but are more convenient than them in describing the process of epidemic spreading. Moreover, we find that the networks with exponential distribution have slower spreading speed than the networks with power-law degree distribution. Numerical simulations have confirmed the theoretical predictions.


Current bibliographies of Neuropeptides prepared by the University of Sheffield Biomedical Information Service


Prions and related neurological diseases


Health systems resilience: meaningful construct or catchphrase?


Singapore should play a strong leadership role in global health


Department of Error


The need for global R&D coordination for infectious diseases with epidemic potential


405-O. Emergency Preparedness Training – Emergency and Community Nurses' Perceived Needs


Patent reports


title: Social influence and spread dynamics in social networks

text: Social networks often serve as a critical medium for information dissemination, diffusion of epidemics, and spread of behavior, by shared activities or similarities between individuals. Recently, we have witnessed an explosion of interest in studying social influence and spread dynamics in social networks. To date, relatively little material has been provided on a comprehensive review in this field. This brief survey addresses this issue. We present the current significant empirical studies on real social systems, including network construction methods, measures of network, and newly empirical results. We then provide a concise description of some related social models from both macro- and micro-level perspectives. Due to the difficulties in combining real data and simulation data for verifying and validating real social systems, we further emphasize the current research results of computational experiments. We hope this paper can provide researchers significant insights into better understanding the characteristics of personal influence and spread patterns in large-scale social systems.


Preparing ED Nurses to Use the Canadian Triage and Acuity Scale With Web-based Learning()


title: On the analysis of a multi-regions discrete SIR epidemic model: an optimal control approach

text: In this paper, we devise a discrete time SIR model depicting the spread of infectious diseases in various geographical regions that are connected by any kind of anthropological movement, which suggests disease-affected people can propagate the disease from one region to another via travel. In fact, health policy-makers could manage the problem of the regional spread of an epidemic, by organizing many vaccination campaigns, or by suggesting other defensive strategies such as blocking movement of people coming from borders of regions at high-risk of infection and entering very controlled regions or with insignificant infection rate. Further, we introduce in the discrete SIR systems, two control variables which represent the effectiveness rates of vaccination and travel-blocking operation. We focus in our study to control the outbreaks of an epidemic that affects a hypothetical population belonging to a specific region. Firstly, we analyze the epidemic model when the control strategy is based on the vaccination control only, and secondly, when the travel-blocking control is added. The multi-points boundary value problems, associated to the optimal control problems studied here, are obtained based on a discrete version of Pontryagin’s maximum principle, and resolved numerically using a progressive-regressive discrete scheme that converges following an appropriate test related to the Forward-Backward Sweep Method on optimal control.


title: Evaluation of immunity to feline infectious peritonitis in cats with cutaneous viral-induced delayed hypersensitivity()

text: Delayed-type hypersensitivity (DTH)-like reactions to feline infectious peritonitis (FIP) virus (FIPV) were induced in the skin of nine cats that were asymptomatic after a previous challenge-exposure with FIPV. Four of the nine previously challenge-exposed cats were negative for virus-neutralizing antibodies against FIPV at the time of intradermal (ID) testing for DTH. Two other cats tested for DTH when acutely ill with clinical FIP did not have cutaneous DTH responses to FIPV. Gross skin reactions to FIPV injected ID were observed in six of nine asymptomatic cats (67%) at postintradermal inoculation hours (PIH) 24, 48, and/or 72. The reactions consisted of focal, 1–5-mm to 2.5-cm diameter indurated or semi-firm, nonerythematous, slightly raised nodules. Microscopically, DTH-like reactions were observed in biopsies taken from the FIPV-inoculated skin of asymptomatic cats at PIH 24 to 72. The lesions consisted of perivascular and diffuse dermal infiltrations by macrophages, lymphocytes, and polymorphonuclear leukocytes (PMN). The dermal infiltrates, which were maximal at PIH 48 or 72, were predominantly mixed inflammatory cells (five of nine cats) or PMN (four of nine cats) at PIH 24, but later were predominantly mononuclear cells (six of nine cats) or mixed inflammatory cells (two of nine cats) at PIH 72. Five of nine cats (56%) with positive DTH skin responses had increased survival times after lethal ID challenge-exposure with FIPV compared to mean survival times in FIPV-naive, non-immune control cats that were DTH-negative when ID challenge-exposed. Four of nine DTH-positive cats (44%) resisted an ID challenge-exposure dose of FIPV that was fatal in both control cats, and two of the four remaining DTH-positive cats survived a third challenge-exposure with highly lethal doses of FIPV given intraperitoneally. Four of the six DTH-positive cats (67%) that died after re-challenge and were necropsied had lesions of noneffusive FIP, suggesting that cellular immunity may also be involved in the pathogenesis of noneffusive disease, whereas both control cats and both DTH-negative cats with clinical disease succumbed to effusive FIP. Seemingly, DTH responses to FIPV can be associated with an increased level of resistance to disease; however, this state of immunity is variable and apparently can be lost with time in some cats.


title: Clinical features of rotavirus gastroenteritis

text: Five hundred and eighteen children under the age of five years admitted to hospital with a diagnosis of gastroenteritis over a twelve-month period were studied prospectively. Rotaviruses were demonstrated by stool electron microscopy (EM) in 132 of these cases (25·4 per cent), but in none of io8 age- and sex-matched controls. Non-specific cases, where no potentially pathogenic organism could be demonstrated in stools submitted for EM, viral and bacterial culture accounted for 46 per cent of cases. If EM of the stools had not been performed the proportion of non-specific cases would have risen to 85 per cent, thus demonstrating the importance of this technique in diagnosis. Rotaviruses were most commonly found in winter and between the ages of six and eighteen months. A history of contact with an adult with diarrheoa, vomiting occuring before diarrhoea, accompanying upper respiratory tract infection (URTI), otitis media and pyrexia and the need for administration of intravenous fluids were all significantly more prominent features of the rotavirus than the non-specific cases of gastroenteritis, and are suggested as pointers to such a diagnosis. Pneumonia is described in three patients as an accompanying illness with rotavirus gastroenteritis.


title: Chronic diarrhoea among HIV-infected adult patients in Nairobi, Kenya

text: OBJECTIVES: Chronic diarrhoea and wasting are well recognized features of AIDS in Africa. However, because of resource constraints few ocmprehensive aetiological studies have conducted in sub-Saharan Africa which have included a broad range of microbiological investigations. We undertook a prospective cross-sectional study of adult patients admitted to a government hospital in Nairobi, Kenya, to determine possible bacterial, mycobacterial, parasitic and viral causes of diarrhoca; to consider which may be treatable; and to relate microbiological findings to clinical outcome. METHODS: Stool specimens from 75 consecutive HIV-seropositive patients with chronic diarrhoca admitted to a Nairobi hospital were subjected to microbiological investigation and results were compared with clinical findings and outcome. Stool samples were cultured for bacteria and mycobacteria and underwent light and electron microscopy; lawns of Escherichica coli were probed for pathogenic types and aliquots were tested for the presence of Clostridium difficile cytotoxin. Blood cultures for mycobacteria and other bacterial pathogens were performed as clinically indicated. RESULTS: Thirty-nine (52%) patients yielded putative pathogens, the most common being Cryptosporidium sp. (17%), Salmonella typhimurium (13%), and Mycobacterium tuberculosis (13%). Of 41 patients investigated for pathogenic Escherichia coli, enteroaggregative E. coli and diffusely adherent E. coli were each found in four patients. Thirty-one (41%) patients died. Detection of cryptosporidium cysts was the single most significant predictor of death (X(2) = 5.2, P<0.05). Many patients did not improve (21; 285) or self-discharged whilst still sick (5; 7%) but five (7%) were diagnosed ante mortem with tuberculosis and treated and a further 13 (17%) showed improvement by time of discharge. CONCLUSIONS: HIV-infected patients with chronic diarrhoea in Nairobi have a poor outcome overall, and even with extensive investigation a putative pathogen was identified in only just over half the patients. The most important step is to exclude tuberculosis: and the most useful investigation appears to be Ziehl-Neelsen staining. Other potentially treatable Gram-negative bacterial pathogens, S. typhimurium, Shigella sp. and adherent E. coli were, however, common but require culture facilities which are not widely accessible for definitive identification. Further studies focussing on simple ways to identify sub-groups of patients with treatable infections are warranted.


title: A patchy model for the transmission dynamics of tuberculosis in sub-Saharan Africa

text: Tuberculosis (TB) spreads through contact between a susceptible person and smear positive pulmonary TB case (TPM+). The spread of TB is highly dependent on people migration between cities or regions that may have different contact rates and different environmental parameters, leading to different disease spread speed in the population. In this work, a metapopulation model, i.e., networks of populations connected by migratory flows, which overcomes the assumption of homogeneous mixing between different regions was constructed. The TB model was combined to a simple demographic structure for the population living in a multi-patch environment (cities, towns, regions or countries). The model consist of a system of differential equations coupling TB epidemic at different strength and mobility between the patches. Constant recruitment rate, slow and fast progression to the disease, effective chemoprophylaxis, diagnostic and treatment are taken into account to make the model including the reality of people in the sub-Saharan African countries. The basic reproduction number ([Formula: see text] ) was computed and it was demonstrated that the disease-free equilibrium is globally asymptotically stable if [Formula: see text] . When [Formula: see text] , the disease-free equilibrium is unstable and there exists one endemic equilibrium. Moreover, the impact of increasing migration rate between patches on the TB spread was quantified using numerical implementation of the model. Using an example on 15 inter-connected patches on the same road, we demonstrated that most people was most likely to get infected if the disease starts in a patch in the middle than in border patches.


Mohs surgery: proclamation, proof, principles, and promise


title: Bovine monoclonal antibody specific for Brucella abortus lipopolysaccharide

text: The development of a bovine monoclonal antibody against Brucella abortus smooth lipopolysaccharide (BM-8) by interspecies fusion of bovine peripheral lymphocytes from an immunized cow and a murine plasmacytoma cell line is described. The twice cloned cell line secreted bovine IgG(1) subclass antibody. Ascites fluid was prepared in pristane treated nu/nu mice by intraperitoneal injection. The pooled ascites fluid was purified by affinity chromatography and the functions of the antibody assessed in various serological tests. The BM-8 antibody did not agglutinate well at a neutral pH, however, under acid conditions it was efficient at agglutinating B. abortus cells. The antibody did not precipitate B. abortus LPS in double agar gel immunodiffusion but was very active in the direct complement fixation test and the indirect enzyme immunoassay, although it was unable to compete with a murine monoclonal antibody in a competitive enzyme immunoassay.


Severe respiratory disease with rhinovirus detection: Role of bacteria in the most severe cases


title: Natural killer (NK) activity and interferon (IFN) production by a fraction of spleen and blood lymphocytes in swine

text: After carbonyl iron treatment and gradient isolation, spleen and blood pig lymphocytes exhibited NK activity and produced IFN after viral induction. Removal of plastic-adherent cells, including the majority of B cells, did not change these activities. The plastic-non-adherent cells were further separated into two subsets of roughly similar size by panning using a monoclonal, anti-T, and anti-null cell antibodies (81+cells). NK activity and IFN production were found in the 81 − cell fraction. A significantly higher proportion of null lymphocytes from blood and of splenic Fc-gamma receptor-bearing lymphocytes was also found among the 81 − cell fraction as compared to the 81 + fraction, without any change among other subsets. Similar proportions of helper (PT4+), cytotoxic (PT8+) and total T cells (MSA4+) were found among lymphocytes bound to target K562 cells and among the whole lymphocyte population. In contrast, lymphocytes that bound K562 cells demonstrated a striking increase in the proportion of Fc-gamma receptor-positive cells of high affinity. These results show that NK cells and IFN-producing cells are mainly included in the same blood and spleen fraction, and suggest that among 81 − cells only those expressing an Fc-gamma receptor of high affinity are active.


Clinical significance of Pneumocystis jirovecii DNA detection by real-time PCR in hematological patient respiratory specimens


title: Daptomycin: A cyclic lipopeptide antimicrobial agent

text: OBJECTIVES: The aims of this article were: to summarize the pharmacology, pharmacokinetics, and efficacy ofdaptomycin; to explore its safety profile; and to discuss its current and potential roles as an antimicrobial therapy. METHODS: A literature search was conducted using the MEDLINE (1966–August 2004) and InternationalPharmaceutical Abstracts (1970–August 2004) databases with the search terms daptomycin, LY146032, and lipopeptide antibiotics. Abstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy and documents submitted to the US Food and Drug Administration were also reviewed. RESULTS: Phase III study results suggest no difference in efficacy or tolerability between daptomycin 4 mg/kgIV QD and vancomycin or semisynthetic penicillins for complicated skin and skin-structure infections. Animal studies suggest daptomycin may be useful for the treatment of endocarditis. Daptomycin is not indicated for pneumonia, with poorer outcomes than conventional treatment It is available as an IV medication and exhibits 92% plasma protein binding in vitro. In healthy adult humans, daptomycin has a volume of distribution of 0.1 Ukg and a plasma elimination half-life of ∼9 hours, and is eliminated primarily by renal excretion (∼54%). In patients with reduced renal function, including those receiving hemodialysis and peritoneal dialysis, the dose interval should be 48 hours. No dosage adjustment appears to be necessary for mild to moderate hepatic impairment. The use of daptomycin in patients with severe hepatic impairment has not been assessed. The most commonly reported adverse events include constipation, nausea, injection-site reactions, headache, and diarrhea. Patients should also be monitored regularly for skeletal muscle toxicity. CONCLUSIONS: Daptomycin may be useful for complicated skin and skin-structure infections and gram-positive pathogens resistant to conventional antimicrobials. However, limited data are currently available for duration of treatment beyond 14 days and at doses >4 mg/kg QD.


title: Picornavirus inhibitors

text: Picornaviruses are among the best understood animal viruses in molecular terms. A number of important human and animal pathogens are members of the Picornaviridae family. The genome organization, the different steps of picornavirus growth and numerous compounds that have been reported as inhibitors of picornavirus functions are reviewed. The picornavirus particles and several agents that interact with them have been solved at atomic resolution, leading to computer-assisted drug design. Picornavirus inhibitors are useful in aiding a better understanding of picornavirus biology. In addition, some of them are promising therapeutic agents. Clinical efficacy of agents that bind to picornavirus particles has already been demonstrated.


title: Human natural interferon-α producing cells

text: Interferons (IFNs) are critical components of the host immune system, serving as antiviral agents, immunomodulators and inhibitors of cell growth. Among peripheral blood mononuclear cells, the primary IFN-α-producing cell is a light density, HLA-DR(+) cell negative for cell surface markers typical for T cells, B cells, monocytes, natural-killer or progenitor cells and has been tentatively the ‘natural’ IFN-producing cell' or NIPC. Although present in very low frequency (approximately 1:1000 among peripheral blood mononuclear cells), the NIPC are very potent, with an individual cell able to produce 1–2 IU of IFN. In this review, the characteristics, phenotype, regulation and relationship of NIPC to human disease are discussed.


Modification of proteins with covalent lipids


title: Rapid and accurate viral diagnosis

text: In recent years, there has been increased recognition of the importance of viral infections. In addition, new antiviral agents have become available. These factors have led to a marked increase in utilization of viral diagnositc services. In this review, both conventional and rapid methods for viral diagnosis are presented, with emphasis on recent advances. The antiviral agents currently available and the major drugs under investigation are also briefly discussed. It is hoped that this review will serve as a useful adjunct for the management of patients with virus infections.


title: Effect of faecal consistency on virological diagnosis

text: A study was set up to investigate the effect of consistency of routine faecal specimens on the diagnostic yield by electron microscopy (EM) and virus isolation. A total of 3078 specimens were characterized as solid, semisolid, or liquid. Of 2568 specimens processed by EM a virus was demonstrated in 8.6% of liquid, 19.9% of semisolid and 25.2% of solid specimens (Chi-squared for lienar trend, P value <0.0001). This observation was valid for both adenovirus (2.4%, 5.0% and 6.6%) and rotavirus (5.2% , 13.6% and 16.6%). Virus isolation was positive in 3.6% of liquid, 17.4% of semisolid and 18.1% of solid specimens. (Chi-squared for linear trend, P value <0.0001). We suggest that solid faecal specimens at the end of an episode of diarrhoea will have a higher diagnostic yield than liquid specimens at the peak of symptoms. Our findings repudiate the commonly held dogma that viruses of gastroenteritis are more likely to be found in liquid than in solid faecal specimens. This finding has important implications for those establishing diagnostic algorithms for the investigation of viral gastroenteritis.


The nature and classification of viruses of man


Poor transmission of seasonal cold viruses in a British Antarctic Survey base


title: A Bovine Monoclonal Antibody to Oestrone/Oestradiol Prepared by a (Murine×Bovine) ×Bovine Interspecies Fusion

text: A heterohybridoma was produced by the fusion of sensitized peripheral blood lymphocytes (PBLs) with a previously derived heteromyeloma, generated by the fusion of bovine PBLs with murine myeloma cells. The sensitized bovine PBLs were collected from a steer immunized with an oestradiol-ovalbumin conjugate. The cell lines resulting from the fusion were screened for the production of bovine antibodies to oestradiol. A stable heterohybridoma was isolated which secreted a bovine IgG(1) to oestrone/oestradiol. The use of sensitized PBLs together with heteromyeloma fusion partners has proved to be a reliable and simple way of producing monoclonal antibodies against specific haptens.


title: A review of enzyme immunoassay for detection of antibody to Brucella abortus in cattle

text: Enzyme immunoassay has gained wide acceptance for serological diagnosis of bovine brucellosis because of its ability to detect antibody of all isotypes unlike the conventional tests. The indirect enzyme immunoassay, however, presents several parameters that require careful analysis. These parameters include the choice of antigen and antiglobulin-enzyme conjugate reagents for use in the assay, dealing with the large amount of data the semi-automatic or automatic assay can generate and the inter-and intralaboratory standardization and quality control. This review considers the various methods described in the literature and, briefly, how some of the problems have been overcome or how they might be dealt with.


Diagnosis of viral disease and the advent of antiviral drugs


title: Hepatic circulation: Potential for therapeutic intervention

text: In recent years, knowledge of the physiology and pharmacology of hepatic circulation has grown rapidly. Liver microcirculation has a unique design that allows very efficient exchange processes between plasma and liver cells, even when severe constraints are imposed upon the system, i.e. in stressful situations. Furthermore, it has been recognized recently that sinusoids and their associated cells can no longer be considered only as passive structures ensuring the dispersion of molecules in the liver, but represent a very sophisticated network that protects and regulates parenchymal cells through a variety of mediators. Finally, vascular abnormalities are a prominent feature of a number of liver pathological processes, including cirrhosis and liver cell necrosis whether induced by alcohol, ischemia, endotoxins, virus or chemicals. Although it is not clear whether vascular lesions can be the primary events that lead to hepatocyte injury, the main interest of these findings is that liver microcirculation could represent a potential target for drug action in these conditions.


A cohort-study of patients suspected for MERS-CoV in a referral hospital in Saudi Arabia


A Tale of Two Systems: Health Reform in China and the United States


Recent developments in assessing and managing serious health threats


title: Bovine monoclonal antibodies to the F5 (K99) pilus antigen of E. coli, produced by murine/bovine hybridomas

text: Lymph node cells from calves immunized with purified pilus antigen of K99(+) enterotoxigenic E. coli (ETEC) were fused with mouse myeloma (NSO) cells, and with non-Ig producing mouse/calf hybridomas or with a bovine Ig-producing mouse/calf/calf secondary hybridoma. Lines secreting bovine monoclonal IgG(1) specific for K99 pilus antigen in an ELISA were obtained in each case. The two lines derived from xenohybridoma fusion partners have been secreting anti-K99 bovine monoclonal antibody for over one year in continual passage. None of the antibodies cross-reacted with other pilus types including K88, CFAI, CFAII, 987P or CP; they all inhibited agglutination of horse RBC (which have a K99 receptor) in the presence of K99 antigen; they showed positive fluorescence in an indirect binding assay on K99(+) ETEC and inhibited K99(+) ETEC adhesion to piglet enterocytes. These antibodies have potential prophylactic and therapeutic use in control and treatment of diarrhoea.


Pandemic Flu: Clinical management of patients with an influenza-like illness during an influenza pandemic


title: Activation of natural killer cells in newborn piglets by interferon induction

text: Natural killer (NK) cell activity in the peripheral blood lymphocytes (PBL) of newborn piglets, normally negligible, was stimulated by in vitro treatment with porcine type I interferon (IFN), and the NK activity of PBL from weaned piglets was augmented by the same treatment. Binding of the PBL to the PK-15 targets used in the single cell cytotoxicity assay for NK activity was not affected by age or by IFN treatment. When newborn piglets were treated with a single intravenous dose at 2 days of age of 0.5 mg/kg of polyinosinic: polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose (poly ICLC), a synthetic IFN inducer, their IFN levels peaked at 6 h post-induction, and NK activity in their PBL peaked at 24 h post-induction at the level normally found in weaned piglets. The NK activity then declined until 7 days post-induction, when it increased again in a similar manner to that in untreated control piglets. Target-binding of the PBL was not affected by poly ICLC treatment of the piglets. Newborn piglets treated with poly ICLC and subsequently exposed to infection with transmissible gastroenteritis (TGE) virus showed a delay in onset of clinical signs of TGE compared with untreated control piglets. It was concluded that NK cells in newborn piglets can be activated by treatment of the piglets with poly ICLC, and that the presence of active NK cells is associated with some increase in resistance to challenge with TGE virus.


title: Activated porcine alveolar macrophages: Are biological response modifiers the answer?

text: We report that 75% of conventionally housed 3- to 4-week-old swine already have detectable activated alveolar macrophages as measured by cytotoxicity of tumor cells. These macrophages can not be further activated by the biological response modifier N-acetylmuramyl-L-alanyl-D-isoglutamine-2H(2)O (MDP). These macrophages lose cytotoxic activity when cultured for 24 h and this loss of activity can not be reversed by MDP. We suggest that MDP biological response modifier therapy of swine alveolar macrophages may not be a useful technique in preventing respiratory disease in swine.


title: Isolation and characterization of lymphocytes from bovine intestinal epithelium and lamina propria

text: The lymphocyte populations of the bovine gut lamina proprial (LP) and epithelial tissues were isolated and characterized with respect to cells bearing surface and cytoplasmic immunoglobulin (Ig). Functional characteristics of cells from the two tissues, including responsiveness to Concanavalin A (Con A), anti-bovine immunoglobulin (anti-Ig), Con A supernatants of bovine peripheral blood lymphocytes (bConA sup) and recombinant human IL-2 (rhIL-2), were also assessed. Less than 1% of the mononuclear cells in the epithelial tissue (IEL) stained for cytoplasmic Ig, and 9% stained positively for surface Ig. IEL did not proliferate in response to anti-Ig, although cells of this population did respond to Con A, bConA sup, and rhIL-2. Twenty-seven percent of bovine gut LP lymphocytes stained for surface Ig, while 39% of these cells were positive for cytoplasmic Ig. LP lymphocytes proliferated in response to all four stimulants used, Con A, anti-Ig, bConA sup and rhIL-2.


title: The production and application of non-rodent monoclonal antibodies in veterinary science

text: The requirement for monoclonal antibodies derived from species other than rats and mice is becoming increasingly realised in veterinary, as well as human, medicine. This paper reviews current knowledge of the production of inter-species hybridomas (heterohybridomas) by the fusion of rodent myeloma cell lines with lymphocytes from species of veterinary importance. To date a number of monoclonal immunoglobulins derived from sheep, cattle, pig, rabbit, mink and primate species have been produced to a variety of different bacterial, viral and nematode pathogens as well as to blood group and MHC determinants and to hormones. The technique opens up a number of possibilities for the future; some of these applications are discussed in relation to the antibodies produced thus far.


title: Methods for Rapid Detection of Human Ocular Viral Infections

text: Recent methods for detection of viruses in clinical specimens include immunofluorescence, immunoperoxidase, immune adherence hemagglutination, radioimmunoassay, enzyme-linked immunosorbent assay (ELISA), and immunoelectron microscopy. Some are useful for the detection of traces of viral antigens but are more complicated and timeconsuming than others. Simple techniques of immunofluorescence and negative stain electron microscopy are used for the rapid detection of viruses in human adenoviral, herpetic, rubella, molluscum contagiosum, and vaccinial infections.


High incidence of viral co-infections and atypical bacterial detection in acute respiratory infections among hospitalized children in the Central Department of Paraguay, 2010–2011


Ebola vaccines: keep the clinical trial protocols on the shelf and ready to roll out


title: Liver cytoprotection by prostaglandins

text: During the last decade intensive work on the relationships between the liver and the arachidonic acid cascade has greatly expanded our knowledge of this area of research. The liver has emerged as the major organ participating in the degradation and elimination of arachidonate products of systemic origin. The synthesis in the liver of arachidonate products derived from the cfyclooxygenase, lipoxygenase and cytochrome P450 system pathways has been demonstrated. The participation of leukotriene B(4) and cysteinyl-leukotrienes as mediators of liver damage and the possible therapeutic usefulness of prostaglandins (PGs) in acute liver injury has attracted the interest of clinicians. This article reviews the essential features regarding the role of arachidonate metabolites in liver disease and specially focuses on the cytoprotective effects on the liver displayed by PGE(2), PGE(1), PGI(2) and synthetic PG analogs in experimental models of liver damage induced by ischemia-reperfusion injury, carbon tetrachloride, bacterial lipopolysaccharide and viral hepatitis and on the possible mechanisms underlying liver cytoprotection in these experimental models. The therapeutic usefulness of PGs in clinical practice is critically analyzed on the basis of available evidence in patients with fulminant hepatic failure and primary graft nonfunction following liver transplantation.


title: The seasonality of rhinovirus infections and its implications for clinical recognition

text: Background: Rhinoviruses are the most common cause of acute respiratory infections. Isolation of rhinoviruses occurs in a distinct and consistent seasonal pattern that can be used to help determine whether an acute respiratory illness is caused by a rhinovirus. Objective: This article reviews information on the seasonality of rhinovirus infection derived from early and recent studies of rhinovirus occurrence and treatment. Methods: PubMed was searched from 1965 to the present to identify all potentially relevant papers. The search terms used were rhinovirus and seasonality. A total of 1998 papers were screened. Results: Rhinoviruses comprise more than three quarters of viruses circulating in early autumn. In some years and perhaps some geographic areas, spring is an even more important time for rhinovirus transmission. Although overall rates of respiratory illness are lower in summer, rhinoviruses are the most frequently isolated virus at this time of year. Other viral agents, including influenza viruses and respiratory syncytial virus (particularly with parainfluenza virus), predominate in the winter. Thus, for most of the year, rhinoviruses are the cause of the majority of acute viral respiratory infections. Conclusion: Understanding the seasonal incidence of rhinovirus infection may help determine how best to employ currently available antirhinoviral agents in patients presenting with symptoms of an acute viral respiratory infection.


title: Intestinal antibody response after vaccination and infection with rotavirus of calves fed colostrum with or without rotavirus antibody

text: The intestinal and systemic antibody response of calves vaccinated and/or challenged with rotavirus was studied employing isotype-specific ELISAs for the detection of IgG(1), IgG(2), IgM and IgA antibodies to rotavirus. Monoclonal antibodies to bovine immunoglobulin isotypes of proven specificity were used as conjugated or catching antibody. Five days after oral inoculation (dpi) of a 5-day-old gnotobiotic calf with rotavirus, IgM rotavirus antibodies were excreted in faeces, followed 5 days later by IgA rotavirus antibodies. The increase in IgM rotavirus antibody titre coincided with the inability to detect further rotavirus excretion. Faeces IgM and IgA rotavirus antibody titres fell to low levels within 3 weeks post infection. IgG(1) and IgG(2) rotavirus antibodies were not detected in faecal samples. In serum, antibodies to rotavirus of all four isotypes were detected, starting with IgM at 5 dpi. Two SPF-calves, which were fed colostrum free of rotavirus antibodies, were vaccinated with a modified live rotavirus vaccine and challenged with virulent rotavirus 6 days later. Upon vaccination, the calves showed an antibody response similar to the response of the infected gnotobiotic calf. Intestinal IgM rotavirus antibodies were excreted before or on the day of challenge and appeared to be associated with protection against challenge infection with virulent virus and rotavirus-induced diarrhoea. In 3 control calves, which were challenged only, the antibody patterns also resembled that of the gnotobiotic calf and again the appearance of IgM rotavirus antibodies coincided with the end of the rotavirus detection period. Two other groups of 3 SPF-calves were treated similarly, but the calves were fed colostrum with rotavirus antibodies during the first 48 h of life. These calves excreted passively acquired IgG(1) and IgG(2) rotavirus antibodies in their faeces from 2 to 6 days after birth. After vaccination, no IgM or IgA antibody activity in serum or faeces was detectable. Upon challenge, all calves developed diarrhoea and excreted rotavirus. Seven to 10 days after challenge low levels of IgM rotavirus antibody were detected for a short period. These data indicate that the intestinal antibody response of young calves to an enteric viral infection is associated with the excretion of IgM antibodies, immediately followed by IgA antibodies. This response is absent or diminished in calves with passively acquired specific antibodies which may explain the failure to induce a protective intestinal immune response by oral vaccination with modified live rotavirus of calves fed colostrum containing rotavirus antibodies.


Next-generation sequencing of the BALF in the diagnosis of community-acquired pneumonia in immunocompromised patients


title: Rapid detection of viral-specific antibodies by enzyme-linked immunosorbent assay (ELISA)

text: 1. 1.|A direct antigen assay using enzyme labelled anti-canine Ig for detecting antibodies to canine parvovirus, 2. 2.|A competitive ELISA using a feline infectious peritonitis virus-specific monoclonal antibody labelled with enzyme, and 3. 3.|A competitive ELISA using an equine infectious anemia virus-specific monoclonal antibody and enzyme labelled antigen, p. 26. The utility and benefits of each of the three approaches is emphasized.


The pathogenesis and frequency of viral infections of man


title: Rechtliche Grundlagen der Berufsausübungsgemeinschaft

text: In professional partnerships not only the premises of the practice, the practice furnishings and the nonmedical personnel are jointly utilized by two or more physicians, but medical personnel can also be jointly employed. As a rule, all income and expenditures are run jointly through the practice. Outwardly, the professional partnership forms a legal unit that is also reflected in the mutual liability of the partners. For the protection of this unit, the professional partnership is allowed to participate in the replacement of the licensing of a retiring partner through the successor, if the licensing is replaced within the professional partnership. Within the framework of the partnership contract, overall great care and in many aspects caution is also warranted. Additionally, the individual situation of the partnership and the individual partners must always be essentially taken into consideration. Even the local treatment situation has an important influence with respect to the requirements planning, particularly on regulation of retirement of a partner. In view of the complexity of the material, the partial aspects of the structure of a contract shown in this article and the appropriate regulatory options can only represent a small excerpt. In view of the legal overlaps from corporate law, laws concerning the medical profession and if necessary licensing laws, a lawyer with the appropriate experience and expertise should be commissioned with the construct of a medical partnership contract.


title: Comment évaluer, orienter et suivre un patient ayant une pneumonie aiguë communautaire ? Une exacerbation de bronchopneumopathie chronique obstructive ?: Évaluation des facteurs de risque d'acquisition, d'évolution compliquée et/ou de mortalité, des signes de gravité. Choix du lieu de la prise en charge et orientation du suivi

text: The purpose of this review was to analyze the literature concerning community-acquired pneumonia (CAP) and acute exacerbations of chronic obstructive pulmonary disease (AECOPD) published in the last five years. CAP and AECOPD are frequent diseases that are to this day still associated with high morbidity and mortality rates. Patient management, especially the choice of the management environment, outpatient or intensive care, depends on the knowledge and recognition of predictors of complications, mortality risk factors, and severity signs to the extent that predictive algorithms have been established. However, research and publications concerning discharge criteria and follow-up of CAP and AECOPD patients is more sparse.


title: Internal ribosome entry sites and dicistronic RNAs in mammalian transgenesis

text: Modification of the genetic content of cultured cells or of whole animals is now a key strategy in both basic biological research and applied biotechnology. Yet obtaining the desired level and specificity of expression of an introduced gene remains highly problematic. One solution could be to couple expression of a transgene to that of an appropriate intact genomic locus. The identification and functional characterization of RNA sequences known as internal ribosome entry sites now offer the possibility of achieving precise control of transgene expression through the generation of dicistronic fusion mRNAs.


title: Changing health in China: re-evaluating the epidemiological transition model

text: This paper reviews the changing health situation in China, which has shown remarkable improvement in the 50 years since the founding of the People’s Republic of China (PRC) in 1949. At first sight this improving health situation follows the classical epidemiological transition model. Just three decades ago health in China was characterised by high rates of infectious disease and early mortality (diseases of poverty) in a mainly peasant society. More recently infectious disease rates have decreased, with corresponding and extended morbidity and mortality associated with an aging population in a rapidly urbanising society. This process has given rise to new health problems, including chronic and degenerative diseases (diseases of affluence). Nonetheless, while there is some validity in the application of the epidemiological transition concept, further analysis demonstrates that China faces a new epidemiological phase, characterised by increasing life expectancy and diseases of affluence coupled with the emergence and re-emergence of infectious diseases. We demonstrate that China’s state policy plays a major role in defining the parameters of health in a Chinese context. We conclude that, today, China is faced with a new set of health issues, including the impact of smoking, hypertension, the health effects of environmental pollution and the rise of HIV/AIDS; however, state policy remains vital to the health of China’s vast population. The challenge for policy is to maintain health reform whilst tackling the problems associated with rapid urbanisation, widening social and spatial inequalities and the emergence of HIV/AIDS and other infectious diseases.


title: Prophylactic and therapeutic activities of 7-thia-8-oxoguanosine against Punta Toro virus infections in mice

text: The biological response modifier 7-thia-8-oxoguanosine was evaluated in mice against the hepatotropic Adames strain of Punta Toro virus. When administered intraperitoneally in divided doses, significant protection from death was conferred at doses of 50 and 100 mg/kg/day given 24 and 17 h pre-virus inoculation, 25–100 mg/kg/day administered 4 h pre- and 3 h post-virus challenge, and 12.5 to 100 mg/kg/day administered 24 and 31 h after virus inoculation. These doses preventing death reduced liver icterus scores, serum alanine aminotransferase and aspartate aminotransferase levels, and liver and serum virus titers relative to placebo controls. Full daily doses administered at 24 h were somewhat less protective to mice than divided daily doses starting at the same time. The initiation of treatment could be delayed as late as 36 h after virus inoculation, resulting in complete protection from mortality at 100 mg/kg/day. This prevention of death occurred despite the acute nature of the infection which resulted in deaths by 96 h in the placebo-treated controls. These results show that 7-thia-8-oxoguanosine has both prophylactic and therapeutic potential as an anti-Phlebovirus agent. Interferon induction appears to be the reason for antiviral activity in this model, since up to 10000 units of interferon/ml were induced in mice 1 h after treatment with 100 mg 7-thia-8-oxoguanosine per kg, and antibody to interferon α/β administered shortly after treatment with the nucleoside negated the antiviral effect.


title: Clinical results obtained in cattle and swine by means of biological immunostimulators()

text: The conditioned infections due to opportunistic organisms, can be controlled by biological immunostimulators. The POLI-IF (Newcastle virus plus endotoxin of E. coli and Freund's incomplete adjuvant) rapidly induces the aspecific immunity. Given twice with 7–10 days interval in between, on occasion of a programmed stress (weaning, transport, crowding) it proved its efficacy in artificially suckled calves and in weaning piglets. The field trials, carried out on 2,782 treated calves in comparison with 2,909 untreated controls and on 4,387 piglets in comparison with 4,461 untreated controls, revealed statistically significant differences for P < 0.005 among the groups of treated and control animals. The immunostimulator reduced the incidence of the disease, dead and discarded animals, as well as it shortened the mean duration of the disease in single heads. Though the way the POLI-IF acts is not perfectly known so far, yet it increases the serum bactericidal activity and the circulating leukocytes, while it induces high levels of IFN. In our opinion the activity of the POLI-IF is bound to 3 factors at least: activation of the complementary fractions, mobilization of the immunocompetent cells, induction of IFN.


title: Mechanism of action of the antiviral compound MDL 20,610

text: The purpose of this study was to probe the antirhinovirus (RV) mechanism of action of MDL 20,610. Evaluation of the compound's effects on RV RNA synthesis, uncoating of neutral red-sensitized RV, plasma membrane penetration by RV, stabilization of RV against heat (56°C) and low pH (5.0) inactivation, and studies with MDL 20,610-resistant RV mutants indicate that MDL 20,610 binds directly to the RV capsid with subsequent inhibition of acid-mediated virion uncoating.


Current research on respiratory viral infections: Third International Symposium


title: The membrane glycoprotein G1 of Uukuniemi virus contains a signal for localization to the Golgi complex

text: Members of the Bunyaviridae family acquire their envelopes by budding into the Golgi complex (GC). The accumulation of the membrane glycoproteins G1 and G2 in the GC probably determines the site of maturation. Here we have studied the intracellular transport and targeting to the GC of G1 and G2 of Uukuniemi virus, a member of the Phlebovirus genus, and report on their expression from cloned cDNAs either together or separately by using a T7 RNA polymerase-driven vaccinia virus expression system. When G1 and G2 were expressed together from a full-length cDNA as the p110 precursor, both proteins were localized to the Golgi complex, as evidenced by colocalization with the Golgi marker enzyme mannosidase II. Immunofluorescent staining indicated that G1 expressed alone also localized to the GC. However, pulse-chase experiments showed that G1 remained endoglycosidase H sensitive. G2 expressed alone remained associated with the endoplasmic reticulum (ER). G2 could be rescued from the ER and transported to the GC by coexpression with G1 from separate mRNAs. Coexpression also increased the efficiency of G1 transport to the GC. With none of the constructs could the glycoproteins be observed on the cell surface. These results show that efficient export of G1 and G2 from the ER requires coexpression of both proteins, in conformity with our previous results showing that G1 and G2 from heterodimeric complexes in the ER. Since G1 expressed alone is retained in the GC, we conclude that G1 contains a retention signal for localization to the GC. G2 might thus become associated with the GC indirectly via its interaction with G1.


title: Sequence and in vitro expression of the phosphoprotein gene of avian pneumovirus()

text: The phosphoprotein (P) gene of two subgroup A strains of avian pneumovirus comprised 855 nucleotides containing only one substantial open reading frame encoding a protein of 278 amino acids, with a predicted M(r) of 30,323. In vitro translation of P mRNA in a wheat germ system resulted in the synthesis of two polypeptides of M(r) 35,000 Comparison of the deduced P protein sequence with that of the known mammalian pneumoviruses revealed overall amino acid identities ranging from 31 to 34.5%, suggesting a distant relationship. However, there was a much higher identity (63.2–68.4%) in a region of 57 residues, which included a heptad repeat sequence.


title: A model for respiratory syncytial virus (RSV) infection based on experimental aerosol exposure with bovine RSV in calves

text: Five conventionally kept calves aged between 17 and 24 days were experimentally infected with bovine respiratory syncytial virus (BRSV) by aerosol in order to mimic the natural infection route. The calves were killed and autopsies performed 7 days after the first virus challenge. The BRSV isolate used induced tracheitis, bronchitis and atelectasis in infected calves. The only virus which could be isolated from the lungs of the calves was BRSV. In addition, Mycoplasma bovirhinis was isolated from the lung or/and trachea of two calves. The clinical and histopathological findings, as well as the detection of BRSV antigens by immunofluorescence in the epithelial cells of lung and trachea, and the reisolation of the virus from bronchoalveolar lavage fluids of all inoculated calves, provided confirmation of successful infection with BRSV.


title: An effective dosage regimen for prophylaxis against rhinovirus infection by intranasal administration of HuIFN-α(2)()

text: Before the prophylactic effect of human interferon α(2) (HuIFN-α(2)) can be tested against naturally acquired rhinovirus infection in a large-scale field trial, it is desirable to show that self-administration of the drug is practical, and to determine the smallest well-tolerated dose likely to produce a worthwhile effect. Here we report that self-administered intranasal interferon can be effective, and show how prophylaxis against rhinovirus infection is affected by both the quantity of interferon, and the interval between a dose and virus challenge. Finally, the medication regimen suggested for use in field trials (3.85 MU 3 times/day) was tested in a double-blind, placebo-controlled trial in volunteers. Although virus challenge was at a time when those being treated with interferon would be most susceptible, a substantial protective effect was still demonstrated.


SVEPM 2018 — Classic problems, future focus, and engagement of stakeholders in veterinary epidemiology and economics, Society of Veterinary Epidemiology and Preventive Medicine Conference, Tallinn, Estonia, 21st–23rd March 2018


title: Prevalence of group A and group B rotaviruses in the feces of neonatal dairy calves from California

text: 136 fecal samples, collected from 47 dairy calves on a calf ranch and in a dairy herd in California, were tested for the presence of group A and group B rotaviruses by reverse transcription-polymerase chain reaction (RT-PCR). Samples were collected from each calf at days 1, 7 and 14. Within the 14 day period, 44 calves (94%) were positive for group A rotavirus and an unexpectedly high number of calves (38 calves, 81%) were positive for group B rotavirus. When these samples were examined by polyacrylamide gel electrophoresis (PAGE), rotavirus was found in 21 calves and all of them had group A electropherotype. Among 25 PAGE positive samples from 21 calves, 17 (68%) were of short electropherotype, 4 (28%) were of long electropherotype and 4 (28%) contained both short and long electropherotype rotaviruses. Group B and short and long electropherotype group A rotaviruses were found in both normal and diarrheic calves.


title: Expression and distribution of the receptors for coxsackievirus B3 during fetal development of the Balb/c mouse and of their brain cells in culture

text: This study was designed mainly to determine the relationships between the expression and distribution of the cellular receptor proteins for coxsackievirus B3 (CVB3) and susceptibility of mouse brain cells during fetal development of Balb/c mice. Immunoblot analysis of fetal extracts demonstrated that the CVB3 receptor proteins were first expressed at day 14 of the fetal stage, and that maximal expression of the cellular receptor occurred at near term or newborn stage. Results also suggested that newborn mouse brain tissue expressed much larger quantities of viral receptor proteins, compared to other tissues. In vitro studies showed that both mouse neurons and astrocytes could be infected by two CVB3 strains, pantropic CVB3 Nancy strain (CVB3N) and myocardiotropic CVB3 Woodruff strain (CVB3W). CVB3N, however, replicated and grew to high titer in primary astrocyte cultures and in primary neuron cultures, whereas, primary astrocyte cultures were relatively resistant to CVB3W. Virus binding assays revealed that CVB3N bound faster and in greater amounts to mouse brain cells than CVBW. These two virus strains, however, were found to share the same receptor specificity by virus competition assays. The number of virus binding sites for CVB3 on newborn mouse brain cells was approximately 1.8 × 10(4) per cell. The data suggested that preferential expression of the cellular receptors on newborn mouse brain cells may be related to their high susceptibilities to CVB3 infection.