bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of M Cells in Intestinal Barrier Function
Authors: KUCHARZIK T. , LÜGERING N. , RAUTENBERG K. , LÜGERING A. , SCHMIDT M. A. , STOLL R. , DOMSCHKE W.
Published: July 2010

Abstract:M cells are known as specialized epithelial cells of the follicle‐associated epithelium of the gastrointestinal tract. As M cells have a high capacity for transcytosis of a wide range of microorganisms and macromolecules, they are believed to act as an antigen sampling system. The primary physiological role of M cells seems to be the rapid uptake and presentation of particular antigens and microorganisms to the immune cells of the lymphoid follicle to induce an effective immune response. In contrast to absorptive enterocytes, M cells do not exert direct defense mechanisms to antigens and pathogens in the gut lumen. Therefore, they provide functional openings of the epithelial barrier. Although M cells represent a weak point of the epithelial barrier, even under noninflamed conditions, there seems to be a balance between antigen uptake and immunological response. The low number of M cells in the gastrointestinal tract and the direct contact to immune cells in the lamina propria usually prevent the occurrence of mucosal inflammation. During chronic intestinal inflammation we observe an increase of M cell number and apoptosis selectively in M cells. M cell damage seems to be responsible for the increase of the uptake of microorganisms that is observed during intestinal inflammation. Under inflammatory conditions in the intestine, the maintenance of the epithelial barrier is broken and M cells seem to play a major role during this process.
Nutrient Transporter Function Studied in Heterologous Expression Systems
Authors: DANIEL HANNELORE
Published: July 2010

Abstract:Although a large number of plasma cell nutrient transport proteins has been cloned in the last couple of years, much remains to be learned about their structure‐function relationships, membrane topology, posttranslational regulation, and bioenergetics of transport. Major progress in the study of the human and animal transporters has come from heterologous expression systems, which offer the benefits of ease of genetic selection and manipulation, short generation time of the organisms in which transporters are expressed, and comparatively high levels of expression of the recombinant proteins. Because our main focus is mammalian peptide transporters, the intestinal peptide transporter, PEPT1, and its renal counterpart, PEPT2, will serve here as models for the analysis of their structure and function when they are heterologously expressed in different cell systems.
Epithelial Barrier Defects in HT‐29/B6 Colonic Cell Monolayers Induced by Tumor Necrosis Factor‐α
Authors: GITTER ALFRED H. , BENDFELDT KERSTIN , SCHMITZ HEINZ , SCHULZKE JöRG‐DIETER , BENTZEL CARL J. , FROMM MICHAEL
Published: July 2010

Abstract: The barrier function of intestinal epithelia relies upon the continuity of the enterocyte monolayer and intact tight junctions. After incubation with tumor necrosis factor‐α TNF‐α, however, the number of strands that form the tight junctions decreases, and apoptosis is induced in intestinal epithelial cells. These morphological changes lead to a rise of transepithelial ion permeability, because the paracellular ion permeability increases and leaks associated with sites of apoptosis increase by number and magnitude. Thus apoptosis and degradation of tight junctions contribute to the increased permeability observed after exposure to TNF‐α. These mechanisms explain clinical manifestations in the inflamed intestinal wall containing cytokinesecreting macrophages‐for example, leak flux diarrhea and invasion of bacterial enterotoxins.
Increased Tight Junction Permeability Can Result from Protein Kinase C Activation/Translocation and Act as a Tumor Promotional Event in Epithelial Cancers
Authors: MULLIN JAMES M. , LAUGHLIN KATHLEEN V. , GINANNI NICOLE , MARANO COLLEEN W. , CLARKE HILARY M. , PERALTA SOLER ALEJANDRO
Published: July 2010

Abstract: Exposure of LLC‐PK1 epithelial cell cultures to phorbol ester tumor promoters causes immediate translocation of protein kinase C‐α (PKC‐α) from cytosolic to membrane‐associated compartments. With a very similar time course, a dramatic and sustained increase in tight junctional (paracellular) permeability occurs. This increased permeability extends not only to salts and sugars but macromolecules as well. Fortyfold increases of transepithelial fluxes of biologically active EGF and insulin occur. Recovery of tight junction barrier function coincides with proteasomal downregulation of PKC‐α. The failure to downregulate activated membrane‐associated PKC‐α has correlated with the appearance of multilayered cell growth and persistent leakiness of tight junctions. Accelerated downregulation of PKC‐α results in only a partial and transient increase in tight junction permeability. Transfection of a dominant/ negative PKC‐α results in a slower increase in tight junction permeability in response to phorbol esters. In a separate study using rat colon, dimethylhydrazine (DMH)‐induced colon carcinogenesis has been preceded by linear increases in both the number of aberrant crypts and transepithelial permeability, as a function of weeks of DMH treatment. Adenocarcinomas of both rat and human colon have been found to have uniformly leaky tight junctions. Whereas most human colon hyperplastic and adenomatous polyps contain nonleaky tight junctions, adenomatous polyps with dysplastic changes did possess leaky tight junctions. Our overall hypothesis is that tight junctional leakiness is a late event in epithelial carcinogenesis but will allow for growth factors in luminal fluid compartments to enter the intercellular and interstitial fluid spaces for the first time, binding to receptors that are located on only the basal‐lateral cell surface, and causing changes in epithelial cell kinetics. Tight junctional leakiness is therefore a promotional event that would be unique to epithelial cancers.
Immunologically Mediated Transport of Ions and Macromolecules
Authors: YU LINDA C. H. , PERDUE MARY H.
Published: July 2010

Abstract:There is increasing evidence supporting the involvement of immune cells and mediators in the control of intestinal physiology. Cell coculture systems and epithelial cell lines have provided convenient model systems for the study of immunomodulation of epithelial function. Abundant cytokines and immune mediators have been shown to directly or indirectly alter epithelial transport of ions and macromolecules. Animal models of hypersensitivity have shown that luminal antigen challenge in the intestine of sensitized rats induces a rapid ion secretory response due to enhanced transepithelial transport of antigen. Transport of ions and macromolecules is highly regulated and an important component of host defense. Dysregulation of epithelial function may play a role in several intestinal disorders, such as inflammatory bowel diseases and food allergy.
Mechanisms of Epithelial Barrier Impairment in HIV Infection
Authors: STOCKMANN MARTIN , SCHMITZ HEINZ , FROMM MICHAEL , SCHMIDT WOLFGANG , PAULI GEORG , SCHOLZ PETER , RIECKEN ERNST‐OTTO , SCHULZKE JÖRG‐DIETER
Published: July 2010

Abstract: Diarrhea and malabsorption due to intestinal dysfunction are common symptoms in HIV infection. The pathophysiologic mechanisms of these alterations are often not known, and the role of HIV per se is still controversially discussed. We measured the epithelial transport and barrier function by means of a miniaturized Ussing chamber system in the duodenum of HIV‐infected patients in different disease stages, determined by the CD4 cell count in the serum as well as symptoms in patients with and without diarrhea. We could show that diarrhea induced by HIV per se is caused by a leak flux mechanism due to impaired epithelial barrier function. Antisecretory therapy does not seem to be useful in these patients, because we did not find increased active ion secretion. Along the course of the HIV infection, the epithelial transport and barrier function varies with HIV disease stage (expressed by CD4 cell status). In addition, an in vitro model was studied to characterize the effect of HIV‐infected human immune cells on the epithelial barrier function using the human colonic epithelial cell line HT‐29/B6. HIV infection of human immune cells induced an increase in cytokine release‐for example, TNF‐α, IL‐1β, IFN‐α, and IFN‐γ‐downregulating the epithelial barrier function of the human colonic epithelial cell line HT‐29/B6. Taken together we postulate a specific stage‐dependent cytokine pattern released from HIV‐infected immune cells in the mucosa, which, corresponding to the HIV disease stage, is responsible for the variation in epithelial function.
Diarrhea in Ulcerative Colitis: The Role of Altered Colonic Sodium Transport
Authors: GREIG EMMA , SANDLE GEOFFREY I.
Published: July 2010

Abstract: In normal human colon, water and sodium (Na+) absorption are directly related. Defective Na+ absorption may therefore be an important factor in the pathogenesis of diarrhea in ulcerative colitis (UC). Electrophysiological studies have revealed profound decreases in channel‐mediated apical Na+ entry and Na+‐K+‐ATPase‐mediated basolateral Na+ extrusion in surface epithelial cells in inflamed human distal colon. Recent molecular biological studies indicate that mucosal inflammation in UC leads to significant decreases in Na+ channel β‐ and γ‐subunit expression in the apical membrane of surface colonocytes, with a marked reduction in the levels of β‐ and γ‐subunit‐specific mRNAs. In addition, basolateral expression of the Na+‐K+‐ATPase α1‐isoform is reduced along the surface cellOcrypt cell axis in UC, although there is no change in the level of the corresponding mRNA. Diarrhea in ulcerative colitis is therefore related, at least in part, to a major defect in electrogenic Na+ absorption, which reflects changes in the levels of expression of critical subunits of both the apical Na+ channel and basolateral Na+‐K+‐ATPase.
Barrier Dysfunction and Crohn's Disease
Authors: MEDDINGS JON
Published: July 2010

Abstract: Crohn's disease is a debilitating illness of unknown etiology. A current hypothesis of disease pathogenesis suggests that this illness represents an abnormal immunological reaction to a luminal antigen. As part of this theory it is suggested that the luminal antigen is delivered to the mucosal immune system by a paracellular route. If this theory is correct several testable predictions can be made. In this manuscript these predictions are presented and the evidence to support or refute them is presented.
Emerging Diseases of Africa and the Middle East
Authors: RWEYEMAMU MARK , PASKIN ROGER , BENKIRANE ABDELALI , MARTIN VINCENT , ROEDER PETER , WOJCIECHOWSKI KRIS
Published: July 2010

Abstract: The term “emerging diseases” has been used recently to refer to different scenarios, all of which indicate changes in the dynamics of disease in the population. Of the OIE List A diseases, major changes have been experienced with rinderpest, peste des petit ruminants (PPR), contagious bovine pleuropneumonia (CBPP), foot‐and‐mouth disease, African swine fever, lumpy skin disease, and Rift Valley fever. Rinderpest represents a success story of the 1990s, thanks to the programs of the Pan African Rinderpest Campaign (PARC). The situation has changed from that of the 1980s when rinderpest was widespread throughout most of Tropical Africa and the Middle East. PPR is a disease that has become of increasing importance throughout Tropical Africa and the Middle East. CBPP, which had previously been reduced to sporadic incidence within endemic areas, invaded new areas, causing heavy mortality. African swine fever has extended to West Africa and to Madagascar, in both regions resulting in heavy losses. Climatic changes in both East and West Africa were associated with an upsurge of Rift Valley fever. Deficiencies in national veterinary services have contributed to failures in early detection and response; in many regions investigation and diagnosis services have deteriorated. The continuing structural adjustment program for national veterinary services will need to take into account their transformation from providers of services (e.g., vaccinations, medicines) to inspection and quality assurance services. Surveillance, early warning, and disease emergency preparedness will need to be pursued more vigorously in Africa and the Middle East as vital components of national veterinary services.
Mitigation of Bioterrorist Threats in the 21st Century
Authors: LOGAN‐HENFREY LINDA
Published: July 2010

Abstract: There is a raising level of awareness and concern that agriculture and food supplies might serve as targets for bioterrorists. To minimize such threats a number of new initiates are urgently needed: 1. Greater levels of financial commitment from federal, state, and international organizations for research on highly infectious diseases and for emergency response infrastructure; 2. Well‐orchestrated emergency response plans based on inter‐agency, inter‐departmental and stakeholder working groups; 3. Teams prepared for risk assessment and risk communication; 4. Modern systems of animal identification and accurate trace‐back for animal movement; 5. Increased biosecurity in intensive production operations; 6. accurate intelligence as to what pathogens pose the highest risks for economic and social impact; 7. Establishment of new international animal and plant disease research networks and partnerships; 8. Strengthen international disease surveillance networks for early detection and intervention; 9. New generations of rapid diagnostic tests for pathogen detection that are practical for field and diagnostic laboratories; 10. Increased level of commitment to pathogen genomics research for molecular epidemiology and vaccine development; 11. New chemical and immunological intervention strategies to prevent or control disease outbreaks; 12. Increased level of training on exotic and emerging animal diseases in basic veterinary education and through continuing education for veterinarians, state and federal field personnel and laboratory diagnosticians.
Culture‐Derived Parasites in Vaccination of Cattle against Tick‐Borne Diseases
Authors: SHKAP VARDA , PIPANO EUGENE
Published: July 2010

Abstract:The major economically important tick‐borne diseases of cattle are theileriosis, babesiosis, anaplasmosis, and cowdriosis. Culture‐derived attenuated schizonts ofTheileria annulatahave proved to be safe for all types of cattle and they protect against tick‐borne theileriosis.T. parvawas also successfully grownin vitro; however, inoculation of cattle with allogeneic schizont‐infected cells resulted in rejection and destruction of the parasites together with the host cells. The number of schizont‐infected cells needed for immunization is greater than forT. annulatatheileriosis. Culture‐propagatedBabesia bovisandB. bigeminawere used for large scale vaccination in the field. An avirulent population ofBabesiaspp. was obtained byin vitrocloning; inoculation of cattle did not induce clinical babesiosis, but produced specific antibodies. Culture‐derived exoantigens ofBabesiaspp. proved to be completely safe for cattle, however, they conferred less protection than live parasites. Cell‐culturedCowdria ruminantiumwas highly infective for susceptible animals but, attenuatedin vitro, could offer a potential source for vaccination.Anaplasma marginale, successfully grown in tick cell culture, may be developed for vaccines. Factors that should be considered in the developing of vaccines against tick‐borne diseases include: the protective immune response to the pathogenic parasite developmental stages, virulence, immunological strain differences, and antigenic variations in cattle and in culture.
Biocontrol of Ticks
Authors: SAMISH MICHAEL
Published: July 2010

Abstract:The increasing resistance of arthropodes to pesticides, their high price, and the growing public demand for safer food and a cleaner environment are obliging animal growers to minimize the use of pesticides by introducing alternative means for tick control. The development of a biological tick control method has been neglected as compared to the control of plant pests or dipterous insects harmful to men and animals. There are abundant observations, but only a few studies have as yet been conducted on pathogens, parasitoides, and predators of ticks. A first attempt at tick biocontrol was made with the introduction of tick‐parasitic wasps from France to the USA and Russia. During the past decade, interest in developing antitick biocontrol agents such as birds (Brazil, Kenya, and Zimbabwe), parasitoides (Kenya and USA), entomopathogenic nematodes (Egypt, Israel, Guadeloupe, and USA), entomopathogenic fungi (Brazil, Cuba, Israel, Kenya, and USA), and bacteria (Brazil) has gained momentum. The reintroduction of oxpecker birds in some areas of Zimbabwe remains up to now the only known successful attempt at tick biocontrol.
International Approach to Eradication and Surveillance for Foot‐and‐Mouth Disease in the Americas
Authors: RODRIGUEZ‐TORRES JOSÉ G.
Published: July 2010

Abstract: Foot‐and‐mouth disease (FMD) was introduced into the Americas in 1870. At that time the disease was described simultaneously in the North coast of the United States of North America, the Province of Buenos Aires in Argentina, the central region of Chile, Uruguay, and South Brazil. At the beginning of the twentieth century the disease spread to the rest of Brazil, Bolivia, Paraguay, and Perú. In 1950 the disease was introduced into Venezuela, and in the same year to Colombia, and from there to Ecuador. The United States of America eradicated an outbreak of FMD in 1929. Outbreaks of FMD were also eradicated from Mexico in 1947 and from Canada in 1952. The last outbreak that occurred in Mexico in 1954 was also eradicated. In 1951 the Americas Animal Health Authorities decided to establish a Pan‐American Foot‐and‐Mouth Disease Center (PANAFTOSA), initially as a special program within the American States Organization (OAS). The center was later transferred to the Pan‐American Health Organization (PAHO). In the early 1970s PANAFTOSA developed a proposal for a continental surveillance system for vesicular diseases, which was approved by Agriculture Ministers at an International Meeting for FMD and Zoonoses (RICAZ). Since then, PANAFTOSA dedicated all efforts to collaborate with each country in the implementation of the system and to receive, analyze, and distribute a weekly report of vesicular diseases. The model was elaborated using coordinate grid maps, one for the South American Continent, others for each country in the region. The reports from each country consist of the grid location for any suspicious outbreak of vesicular disease. Using the information gathered during visits to the countries, as well as weekly reports, and by studying the most frequent animal movements within the region, PANAFTOSA developed a proposal for FMD eradication. This plan was approved by the Government of South America and implemented in cooperation with PANAFTOSA. The hemispheric plan for FMD eradication (PHEFA), has been implemented and today Chile and Uruguay are FMD free without vaccination; Argentina, Paraguay, and the states of Rio Grande do Sul and Santa Catarina in Brazil are also recognized by the OIE to be FMD Free, with vaccination. The use of the continental surveillance system is the main strategy for achieving the eradication of FMD in South America. At this time PANAFTOSA is working to improve the system, and to add other diseases indicated by the governments of the Americas.
Rapid Recovery and Identification of Anthrax Bacteria from the Environment
Authors: KIEL JOHNATHAN L. , PARKER JILL E. , ALLS JOHN L. , KALNS JOHN , HOLWITT ERIC A. , STRIBLING LUCILLE J.V. , MORALES PEDRO J. , BRUNO JOHN G.
Published: July 2010

Abstract: Bacillus anthracis has been recognized as a highly likely biological warfare or terrorist agent. We have designed culture techniques to rapidly isolate and identify “live” anthrax from suspected environmental release. A special medium (3AT medium) allows for discrimination between closely related bacilli and non‐pathogenic strains. Nitrate was found to be a primary factor influencing spore formation in Bacillus anthracis. Nitrate reduction in anthrax is not an adaptation to saprophytic environmental existence, but it is a signal to enhance environmental survival upon the death of the anthrax host, which can be mimicked in culture.
Ticks Associated with Wild Animals in the Nhecolândia Pantanal, Brazil
Authors: BECHARA G. H. , SZABÓ M. P.J. , DUARTE J. M.B. , MATUSHIMA E. R. , PEREIRA M. CAMPOS , RECHAV Y. , KEIRANS J. E. , FIELDEN L. J.
Published: July 2010

Abstract:A study of ticks associated with wild animals was carried out from September 1996 to April 1998 at the Fazenda Alegria (21,000 ha), in the Nhecolândia Pantanal, State of Mato Grosso do Sul, Brazil, a sunken plain bordering the upper Paraguay river, located 19 × 08′S; 56 × 46′W. A total of 81 wild animals (13 species, 6 orders) were captured with the aid of nets, and ticks were found on 63 (78%). Tick species identified includedBoophilus microplus(Canestrini),Amblyomma cajennense(F.),A. parvum(Aragão),A. pseudoconcolor(Aragão),A. scalpturatum(Neumann),A. nodosum(Neumann),A. ovale(Koch), andA. tigrinum(Koch). Dragging from grasslands (campos) yielded negative results compared to the high concentration of ticks, mainly nymphs, that were collected from leaves in the forests (capão). Predominance of immature instars (Amblyomma genera) was observed in the end of winter (August‐September). Ticks were associated mainly with coatis, deer (Mazama gouazoubira) and anteater, and these animals may play a role in the epidemiology of tick‐transmitted pathogens in the Pantanal if one considers their co‐existence with local domestic animals.
Laboratory Evaluation of Pathogenicity of Entomogenous Nematodes to African Tick Species
Authors: KAAYA GODWIN P. , SAMISH MICHAEL , GLAZER ITAMAR
Published: July 2010

Abstract: Five strains of entomogenous nematodes, Steinernema carpocapsæ strains DD, Mexican, SR, and Heterorhabditis bacteriophora strains 1S5 and HP88, were tested for their pathogenicity to various developmental stages of five African tick species namely; Rhipicephalus appendiculatus, R. evertsi, Amblyomma variegatum, A. gemma, and Boophilus decoloratus. In engorged female R. appendiculatus, all nematodes at a concentration of 1,000 infective juveniles (IJ)/dish, except S. carpocapsæ Mexican strain, induced high mortalities (56‐100%), whereas in engorged female R. evertsi, only S. carpocapsæ DD and H. bacteriophora HP88 induced high mortalities (78% and 56%, respectively). In engorged B. decoloratus, S. carpocapsæ DD, Mexican, SR and H. bacteriophora HP88 (100 IJ/dish) induced mortalities of 85%, 65%, 80%, and 100%, respectively. In all cases, except for S. carpocapsæ Mexican strain, a higher concentration (5,000 IJ/dish) did not result in higher mortality than occurred with 1,000 IJ/dish. Unfed females and immature stages of ticks were found to be generally resistant to the nematodes. The feasibility of using entomogenous nematodes for biological control of African tick species are briefly discussed.
The Eradication of Contagious Bovine Pleuropneumonia from South Western Africa: A Plan for Action
Authors: WINDSOR ROGER S.
Published: July 2010

Abstract: Contagious bovine pleuropneumonia (CBPP) caused by the Mycoplasma mycoides subspecies mycoides SC is one of the major plagues affecting cattle. With the imminent eradication of rinderpest from Africa, CBPP will become the major epidemic disease on the continent, because the majority of countries in sub‐Saharan Africa have the infection in their cattle. There is an enclave of CBPP on the borders of Angola, Botswana, Namibia, and Zambia. There has been endemic infection in the cattle herds on the borders of Angola and Namibia for more than 100 years, with irregular spread from these animals to the cattle of Botswana or Zambia. However, much of Angola and Namibia and all of Botswana and Zambia are currently free from the disease. This paper explains the origins of the problem and describes the current disease situation. A plan for the eradication of CBPP from this area is proposed and discussed. If this plan is successful it will release valuable resources to tackle other constraints on livestock and food production. Furthermore, it will act as a model for the eradication of CBPP from the remainder of the continent.
Emergence of Nipah Virus in Malaysia
Authors: UPPAL P. K.
Published: July 2010

Abstract: A pig‐borne virus causing viral encephalitis amongst human beings in Malaysia was detected in 1997 by the Ministry of Health. Initially, the disease was considered to be Japanese encephalitis. Subsequently, it was thought to be a Hendra‐like viral encephalitis, but on 10th April, 1999 the Minister of Health announced this mysterious and deadly virus to be a new virus named Nipah virus. The virus was characterized at CDC, Atlanta, Georgia. The gene sequencing of the enveloped virus revealed that one of the genes had 21% difference in the nucleotide sequence with about 8% difference in the amino acid sequence from Hendra virus isolated from horses in Australia in 1994. The virus was named after the village Nipah. In all, the Ministry of Health declared 101 human casualties, and 900,000 pigs were culled by April, 1999. The worst affected area in Malaysia was Negri Sembilan. The symptoms, incubation period in human being and pigs, animal to human transmission, threat of disease to other livestock, and control program adopted in Malaysia is described.
Survey of Small Rodents and Hematophagous Flies in Three Sentinel Farms in a Costa Rican Vesicular Stomatitis Endemic Region
Authors: JIMENEZ ANA E. , HERRERA FLOR VARGAS , SALMAN MO , HERRERO MARCO V.
Published: July 2010

Abstract: A survey of rodents and hematophagous flies was conducted on three farms located in an area endemic for vesicular stomatitis to determine the species composition of each zoological group occurring in these areas. Eleven species of small rodents were collected and identified. Individuals from forty‐nine species of hematophagous flies of the families Ceratopogonidæ, Culicidæ, and Phlebotominæ were captured and identified. The species compositions in each group were compared between farms. Rodents were tested for antibodies to vesicular stomatitis, New Jersey and Indiana serotypes. Seven species had antibody titers greater than 1:10. Attempts to isolate the virus produced negative results for all the species tested.
Laboratory and Field Evaluation of Entomogenous Fungi for Tick Control
Authors: KAAYA GODWIN P.
Published: July 2010

Abstract: Aqueous and oil‐based formulations of two entomogenous fungi, Beauveria bassiana and Metarhizium anisopliæ were tested for their efficacy against the three major species of African ticks; namely, Amblyomma variegatum, Rhipicephalus apendiculatus, and Boophilus decoloratus. Both fungal species and formulations were observed to induce high mortalities, especially in the larvæ. The oil‐based formulation was found to be more effective than the aqueous formulation. Monthly application of aqueous formulations of B. bassiana and M. anisopliæ on vegitation in paddocks significantly reduced numbers of the tick R. appendiculatus on cattle. Possibilities for using entomogenous fungi in tick control, alone, or in combination with the conventional acaricides are discussed.
Present and Future Technologies for Tick Control
Authors: GEORGE JOHN E.
Published: July 2010

Abstract: Arsenic dips were the first effective method for controlling ticks and tick‐borne diseases, and were used in many parts of the world for over 50 years before resistance to the chemical became a problem. Until organochlorine products became available about 1946 as alternatives to arsenic, significant losses occurred in cattle herds exposed to arsenic‐resistant tick strains. Since the discovery of organochlorines, virtually every chemical group of pesticides developed for the control of arthropods is represented among the list of products employed for the control of ticks on cattle. The evolution of tick resistance to acaricides has been a major determinant of the need for new products. The variety of procedures for treating animals with acaricides ranges from dipping cattle to injecting systemic acaricides, but regardless of the treatment method used, producers need to know and follow proper application procedures to derive maximum benefits. The possibility of stocking with cattle breeds that acquire pronounced resistance to ticks or using recombinant antigen antitick vaccines are the most promising alternatives to acaricides. Most ranchers depend completely on acaricides to control ticks, but do not have access to guidelines on how to make a profit from their tick control program or how to detect and resolve problems with resistance to acaricides. Extension programs are needed to help ranchers manage animal health problems, including how to control ticks and tick‐borne diseases.
Generation of Cytotoxic T Lymphocytes and Cytostatic Acting Cells in T. annulata‐Immune Cattle
Authors: AHMED J. S. , WIEGERS P. , RITZ H. , HARTWIG H. , SCHEIN E. , SCHNITTGER L.
Published: July 2010

Abstract: Cattle immunized against Theileria annulata with schizont containing autologous cell lines are immune to challenge with a homologous parasite strain. Two cell types have been detected in the peripheral blood of the immunized animals: cytotoxic T lymphocytes (CTL) and cytostatic acting cells (CAC). Killing the target cells by CTL is infection associated and is MHC class I restricted. Hence, no cytotoxicity was observed against target cells that were treated with the theilericidal drug buparvaquone or autologous Con A‐blasts. The growth inhibition of CAC is MHC unrestricted, and not mediated by cytokine interferon gamma (IFN‐γ).
Immunological Control of Ticks through Vaccination with Boophilus microplus Gut Antigens
Authors: DELA FUENTE JOSÉ , RODRÍGUEZ MANUEL , GARCÍA‐GARÍ JOSÉ C.
Published: July 2010

Abstract: The control of tick infestations and the transmission of tick‐borne diseases remain a challenge for the scientific community. Traditional control methods have been only partially successful. Recently, vaccination with recombinant Boophilus microplus gut antigens has been shown to control tick infestations. Our Bm86‐containing vaccine formulation (Gavac™) has been effective for the control of artificial infestations of B. annulatus, B. decoloratus, and chemically sensitive and resistant B. microplus strains from Australia, Africa, America, and Iran. Preliminary results with Hyalomma spp. and Rhipicephalus spp. suggest partial cross protection. In field trials, vaccination with Gavac controlled B. microplus and B. annulatus infestations and reduced the transmission of babesiosis, resulting in important savings for the cattle industry. Different degrees of susceptibility to the vaccination with Bm86 and sequence variations in the Bm86 locus have been reported. The Bm95 antigen was isolated from the Argentinean Bm86‐resistant B. microplus strain A. A Bm95‐based vaccine was used to protect cattle against tick infestations under production conditions with similar results to that obtained with Gavac. The Bm95 antigen from strain A was able to protect against infestations with Bm86‐sensitive and Bm86‐resistant tick strains, thus suggesting that Bm95 could be a more universal antigen in protecting cattle against infestations by B. microplus strains from different geographical areas. These results clearly demonstrate the advantage and possibilities for the immunological control of ticks.
Bidirectional Heterologous Desensitization of Opioid and Chemokine Receptors
Authors: ROGERS T. J. , STEELE A. D. , HOWARD O. M.Z. , OPPENHEIM J. J.
Published: July 2010

Abstract:Opioids are known to suppress a number of elements of the immune response, including antimicrobial resistance, antibody production, and delayed‐type hypersensitivity. Phagocytic cells may be particularly susceptible to opioid administration, since reduced production of the cytokines IL‐1, IL‐6 and TNF‐α, monocyte‐mediated phagocytosis, and both neutrophil and monocyte chemotaxis have all been well established. Earlier studies have shown that both μ‐ and δ‐opioid agonists induce a chemotactic response in monocytes and neutrophils. In addition, μ‐ and δ‐opioid administration inhibited the chemotactic response of these cell populations to a number of chemokines through a process of heterologous desensitization. We report here that μ‐, δ‐, and κ‐opioid agonists also induce a chemotactic response in T lymphocytes. Using the human T‐cell line Jurkat, we have confirmed previous observations that pre‐incubation with met‐enkephalin (MetEnk), an endogenous opioid agonist, prevents the subsequent chemotactic response to the chemokine RANTES. On the other hand, treatment with MetEnk does not alter the response to the chemokine SDF‐1α. Moreover, we found that pretreatment with RANTES prevented a subsequent response of monocytes to the μ‐opioid agonist DAMGO. These results suggest that activation of members of the opioid and chemokine receptor families leads to downregulation of each other's leukocyte migratory activities.
Oncology in Neuroimmunomodulation: What Progress Has Been Made?
Authors: CONTI ARIO
Published: July 2010

Abstract: In 1987 in Dubrovnik, Yugoslavia, N.H. Spector named a new discipline: Neuroimmunomodulation. R. Ader called this new discipline psychoneuroimmunomodulation when the major emphysis was on its behavioral aspects. Neuroimmunomodulation (NIM) is devoted to the study of the interactions at different morphologic and functional levels among the immune, nervous, and endocrine systems. In fact, this science is the modern manifestation of an old science: in the words of B.D. Jankovic (1987), “Neuroimmunomodulation is a modern reflection in neurosciences and immunosciences of the ideas and experience of philosophers and ingenious observers of ancient Egypt, Greece, China, India, and other civilizations that the mind is involved in the defense against diseases.” Twelve years ago NIM was regarded by many conventional scientists almost as a form of witchcraft. Today it may be the fastest growing area of biomedical science research in the world. Important clinical applications will not be far behind. NIM research has also progressed in the field of oncology research. Topics such as treatment of hormone‐dependent cancer with analogues of hypothalamic hormones, the role of opioids and T cells in cancer, stress‐cancer‐immune connections, the anticancer role of melatonin and cytokines, immunotherapy of cancer, and the role of psychotherapy in cancer patients represent some lines of research that have been or are being investigated by scientists. Some areas remain to be thoroughly investigated such as the influence of physical exercise (sports), music (classical or modern), and/or relaxation techniques (e.g. yoga) on the development of human cancer. This paper reviews the role of NIM in oncology and provides some perspectives for further research and development of clinical applications.
Mechanisms of Behavioral and Neuroendocrine Effects of Interleukin‐1 in Mice
Authors: NEVEU PIERRE J. , LIÈGE STÉPHANE
Published: July 2010

Abstract: Interleukin‐1β is a key molecule in brain‐immune interactions that, apart from its immune effects, stimulates the hypothalamo‐pituitary‐adrenal (HPA) axis and induces behavioral alterations. However, its physiological role during stress responses remain to be elucidated. The possible mechanisms involved in IL‐1‐mediated stimulation of the HPA axis during stress were assessed by using different approaches. They were first studied in mice deficient for the IL‐1β‐converting enzyme (ICE) gene. Mature IL‐1β derives from a precursor, the pro‐IL‐1β, devoid of any conventional signal sequence that is mainly processed by ICE. After immune or stress stimulation, ICE‐deficient mice were shown to have a hyperactive HPA axis and to able to produce immunoreactive IL‐1β. This indicates that the greater reactivity of the HPA axis could result from a higher sensitivity to non‐ICE‐matured IL‐1β, as suggested by a higher basal transcription of hypothalamic IL‐1 receptor type I (IL‐1 RI) in ICE‐deficient mice. The biological effects of IL‐1β are mediated by IL‐1 RI associated with the IL‐1 receptor accessory protein (IL‐1RAcP). IL‐IRAcP is an essential component for IL‐1 action at the periphery, but its role in the brain is not well known. Therefore, the effects of i.c.v. IL‐1β were studied in IL‐1RAcP‐deficient mice. In normal mice, i.c.v. IL‐1β depresses peripheral immune responses, induces the production of plasma IL‐6, and stimulates the HPA axis. None of these effects were observed in IL‐1RAcP‐deficient mice, indicating that IL‐1RAcP is necessary for the induction of the main neuroendocrine and immune effects of central IL‐1β. In normal mice, the role of IL‐1β was assessed by pretreating the animal with the IL‐1 receptor antagonist (IL‐1Ra). IL‐1Ra did modify the activation of the HPA axis observed during stress, except when the animals were previously sympathectomized. This suggests that the sympathetic nervous system can downregulate the IL‐1β‐induced stimulation of the HPA axis. Finally, the modulation of the production and physiological activities of IL‐1 were studied in normal mice, taking advantage of interindividual differences in brain‐immune interactions linked to cerebral lateralization. Behavioral/brain lateralization was shown to be related to behavioral response to peripheral administration of IL‐1, and to the production of IL‐1 and IL‐6 in response to LPS. This suggests that cytokines, and especially IL‐1β, may represent one of the factors responsible for interindividual differences in brain‐immune interactions.
Tumor Necrosis Factor‐α Induces Neuronal Death by Silencing Survival Signals Generated by the Type I Insulin‐Like Growth Factor Receptor
Authors: VENTERS H. D. , DANTZER R. , KELLEY K. W.
Published: July 2010

Abstract: Within the central nervous system, the proinflammatory cytokine tumor necrosis factor (TNF)‐α is best characterized by its ability to directly foment signals of death. However, recent evidence suggests that TNF‐α also promotes neurodegeneration through inhibition of a vital survival signal, insulin‐like growth factor‐I (IGF‐I). By inhibiting essential components of the IGF‐I survival response, such as phosphatidylinositol 3′‐kinase (PI 3‐kinase), low nontoxic concentrations of TNF‐α indirectly trigger the death of neurons. We suggest that this inhibition of survival signaling is a pathophysiologically relevant action of TNF‐α in the brain. This type of cross‐talk by which vastly different receptors utilize shared intracellular substrates is potentially applicable to a broad number of receptors that are coexpressed on the same cell. The use of neuronal growth factors in the treatment of neurodegenerative diseases, such as cerebral ischemia and the AIDS dementia complex, may prove much more effective if the elevated expression of TNF‐α in these disorders is neutralized.
The Role of α‐MSH as a Modulator of Cutaneous Inflammation
Authors: LUGER T. A. , BRZOSKA T. , SCHOLZEN T. E. , KALDEN D.‐H. , SUNDERKÖTTER C. , ARMSTRONG C. , ANSEL J.
Published: July 2010

Abstract: Among various neuropeptides such as substance P, calcitonin gene‐related peptide and others, α‐melanocyte‐stimulating hormone (α‐MSH) was found to be produced in the skin. Moreover, melanocortin receptor 1 (MC‐1R), which is specific for α‐MSH and ACTH, is expressed in the skin on keratinocytes, dendritic cells, macrophages and endothelial cells. In monocytes, macrophages and dendritic cells α‐MSH inhibits the production and activity of immunoregulatory and proinflammatory cytokines such as IL‐2, IFN‐γ, TNF‐α, and IL‐1. It downregulates the expression of costimulatory molecules such as CD86 and CD40 and induces the production of suppressor factors such as the cytokine synthesis inhibitory factor IL‐10. On endothelial cells α‐MSH is capable of downregulating the LPS‐induced expression of adhesion molecules such as vascular cell adhesion molecule (VCAM) and E‐selectin. Moreover, the LPS‐induced activation of transcription factors such as NFκB is downregulated by α‐MSH. In a mouse model i.v. or topical application of α‐MSH was found to inhibit the induction phase as well as the effector phase of contact hypersensitivity (CHS) reactions and to induce hapten‐specific tolerance. These findings indicate that the production of immunosuppressing neuropeptides such as α‐MSH by epidermal cells may play an essential role during the pathogenesis of immune and inflammatory reactions in the skin.
Neuropeptide Regulation of Immunity: The Immunosuppressive Activity of Alpha‐Melanocyte‐Stimulating Hormone (α‐MSH)
Authors: TAYLOR A. W. , YEE D. G. , NISHIDA T. , NAMBA K.
Published: July 2010

Abstract: The ocular microenvironment is an extreme example of regional immunity. Within its microenvironment, expression of delayed type hypersensitivity (DTH) is suppressed. This immunosuppression is mediated in part by the constitutive expression of α‐MSH. Previously we have found that α‐MSH suppresses the production of IFN‐γ by activated effector T cells. Recently we have found that α‐MSH can mediate induction of TGF‐β‐producing T cells that act as regulatory T cells. This has encouraged us to further examine the potential for α‐MSH to suppress T cell‐mediated inflammation (autoimmune disease) and to regulate lymphokine production by effector T cells. When α‐MSH was injected i.v. into mice at the time of peak retinal inflammation, the severity of experimental autoimmune uveitis (EAU) was significantly suppressed. Effector T cells activated in vitro in the presence of α‐MSH proliferated and produced IL‐4 and enhanced levels of TGF‐β while their IFN‐γ and IL‐10 production was suppressed. The α‐MSH‐treated T cells functioned as regulatory T cells by suppressing in vitro IFN‐γ production by other inflammatory T cells. This regulatory activity was the function of α‐MSH‐treated CD4+ CD25+ T cells. Therefore, α‐MSH mediates immunosuppression by inducing a differential expression of lymphokine production and by inducing activation of regulatory functions in T cells. This implies that α‐MSH may take part in regional mechanisms of immunosuppression and possibly peripheral tolerance. Thus, α‐MSH can be used to suppress autoimmune disease and possibly reestablish tolerance to autoantigens.
Nerve Growth Factor and Neuroimmune Interactions in Inflammatory Diseases
Authors: STANISZ ANDREW M. , STANISZ JOLANTA A.
Published: July 2010

Abstract: Discovered almost 50 years ago, nerve growth factor (NGF) has been extensively studied in various biological systems. NGF has recently been suggested to play an important role in mediating and/or regulating immune response, in addition to its trophic and tropic effects on nerve growth and regeneration It is clear that in complex interactions between immune cells and nervous system NGF plays a central role. We have only just begun to identify and understand the direct mechanisms by which NGF activates target cells, the precise identity of the target cells, and the particular factors released from target cells. Nerve growth factor together with possibly other neurotrophins such as BDNF (brain‐derived nerve growth factor), GDNF (glial‐derived nerve growth factor) or NT3 are important modulators of immunity. More detailed studies are needed at the receptor, mediator and cellular levels to better understand the neuroimmunomodulatory properties of neurothrophins and NGF. The nature of the involvement of NGF in inflammation and inflammatory diseases remains a particularly interesting question. By blocking NGF or mediators released upon NGF activation, we are able to control the progress of inflammation, thereby opening many therapeutic opportunities for the future.
Neuropeptide Control of Bone Marrow Neutrophil Production: A Key Axis for Neuroimmunomodulation
Authors: BROOME CAROLINE S. , MIYAN JALEEL A.
Published: July 2010

Abstract:Nerve fibers project into the bone marrow and terminate in association with stromal cells. Nerve terminals are also associated with antigen‐processing and ‐presenting cells throughout the body and have been shown to be important in leukocyte trafficking and wound healing as well as hemopoiesis. Here we show that neuropeptide input to the bone marrow is vital to normal granulopoiesis and that deletion of the neuropeptides, substance P, and calcitonin gene‐related peptide (CGRP), with the neurotoxin, capsaicin, abrogates normal blood cell production. Norepinephrine, neurokininsaand 2, and vasoactive intestinal peptide all have inhibitory effects onin vitroCFU‐GM colony formation. Substance P, neurokinin 1, nerve growth factor, and CGRP have stimulatory effects on CFU‐GM. Furthermore,in vitroexperiments show that, apart from CGRP, all the neuroactive substances we tested operate through effects on accessory cells, stimulating the release of regulatory molecules that have a direct effect on purified CFU‐GM.
The Immune System and Schizophrenia: An Integrative View
Authors: MÜLLER NORBERT , RIEDEL MICHAEL , GRUBER RUDOLF , ACKENHEIL MANFRED , SCHWARZ MARKUS J.
Published: July 2010

Abstract:Immune alterations in schizophrenia have been described for decades. Modern immunological methods and new insights into the highly developed and functionally differentiated immune system allow an integrative view of both the older and the recent findings of immunological abnormalities in schizophrenia. Both the unspecific and the specific arms of the immune system seem to be involved in the dysfunction of the immune system in schizophrenia. The unspecific, “innate” immune system shows signs of over‐activation in unmedicated schizophrenic patients, as indicated by increased monocytes and γδ‐cells. Increased levels of interleukin‐6 (IL‐6) and the activation of the IL‐6 system in schizophrenia might be the result of the activation of monocytes/macrophages, too. On the other hand, several parameters of the specific cellular immune system are blunted, such as, for example, the decreased T helper‐1 (TH‐1)‐related immune parameters in schizophrenic patients bothin vitroandin vivo. It seems that a TH‐1‐TH‐2 imbalance with a shift to the TH‐2 system is associated with schizophrenia. During antipsychotic therapy with neuroleptics, the specific TH‐1‐related immune answer becomes activated, but in addition the B cell system and antibody production increase.
Prenatal Influences on Neuroimmune Set Points in Infancy
Authors: COE CHRISTOPHER L. , LUBACH GABRIELE R.
Published: July 2010

Abstract: Many factors during fetal life and early infancy have been found to affect the development of immune responses in animals. This study investigated whether acute exposure of the fetal monkey to high levels of corticosteroids would also have a lingering effect on the expression of immune responses still manifest postpartum in yearling juveniles. One month prior to parturition, pregnant rhesus monkeys were administered dexamethasone for two days. Lymphocyte proliferative responses to mitogen were then examined in their offspring when they were between 1.0‐1.5 years of age. In addition, cell sensitivity to corticosteroid feedback was assessed by testing the ability of a gradation of cortisol doses to inhibit proliferation. Monkeys generated from dexamethasone‐treated pregnancies tended to have lower responses to concanavalin A. Further, their cells were less sensitive to in vitro incubation with cortisol, suggesting that elevated adrenal activity in vivo had downregulated hormone receptors on their cells. These findings concur with the view that steroidal hormones in utero can influence the fetal immune system, resulting in prolonged effects on immune responses after birth. The similarity of the dexamethasone condition to the clinical treatment used in obstetrical practice raises a potential concern about the widespread antenatal exposure of premature infants to steroidal drugs.