bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of Galanin in Memory Pathways
Authors: MILLER MARGARET A.
Published: February 2006

Abstract: Based on early immunocytochemical findings, galanin (GAL) was postulated to function as an inhibitory cotransmitter in rat cholinergic memory pathways. However, recent studies indicate that in the basal state GAL is not widely expressed by forebrain cholinergic neurons in rats. Inhibition of cholinergic transmission by cosecreted GAL may be enhanced under certain conditions, because GAL gene expression in the cholinergic basal forebrain is significantly increased prior to puberty and following nerve growth factor treatment. Other sources of GAL in rat septohippocampus that could interact with cholinergic pathways include noradrenergic neurons in the locus ceruleus and vasopressinergic neurons in the bed nucleus of the stria terminalis (BST) and medial amygdala (Me). GAL is extensively colocalized within these steroid‐sensitive cell groups where its expression is upregulated by gonadal hormones. GAL, acting via the GALR1 receptor subtype, does not appear to directly regulate the activity of cholinergic neurons, but it may regulate the release of vasopressin and GAL into septohippocampus from BST/Me neurons.
Modulation of Acetylcholine and Serotonin Transmission by Galanin: Relationship to Spatial and Aversive Learning
Authors: ÖGREN S. O. , SCHÖTT P. A. , KEHR J. , YOSHITAKE T. , MISANE I. , MANNSTRÖM P. , SANDIN J.
Published: February 2006

Abstract:This paper presents evidence that galanin is a potentin vivomodulator of basal acetylcholine release in the rat brain with qualitatively and quantitatively differential effects in the dorsal and ventral hippocampus. Galanin perfused through the microdialysis probe decreased basal acetylcholine release in the ventral hippocampus, while it enhanced acetylcholine release in the dorsal hippocampus. Galanin (3 nmol/rat) infused into the ventral hippocampus impaired spatial learning acquisition, while it tended to facilitate acquisition when injected into the dorsal hippocampus. These effects appear to be related to activation of GAL‐R1 (ventral hippocampus) and GAL‐R2 (dorsal hippocampus) receptors, respectively. However, the effects of galanin on acetylcholine release and on spatial learning appear not to be directly related to cholinergic mechanisms, but they may also involve interactions with noradrenaline and/or glutamate transmission. Galanin administered into the lateral ventricle failed to affect acetylcholine release, while this route of administration produced a long‐lasting reduction in 5‐HT release in the ventral hippocampus, indicating that galanin is a potent inhibitor of mesencephalic 5‐HT neurotransmissionin vivo. Subsequent studies supported this hypothesis, showing that the effects on 5‐HT releasein vivoare most likely mediated by a galanin receptor in the dorsal raphe. The implications of these findings are discussed in relation to the role of acetylcholine in cognitive functions in the forebrain and the role of the raphe 5‐HT neurons in affective disorders.
PCR Analysis and Spatial Repartition of Trypanosomes Infecting Tsetse Flies in Sidéradougou Area of Burkina Fasoa
Authors: DE, LA ROCQUE S. , LEFRANCOIS T. , REIFENBERG J. M. , SOLANO P. , KABORE I. , BENGALY Z. , AUGUSSEAU X. , CUISANCE D.
Published: February 2006

ABSTRACT: A parasitological and entomological survey was conducted in the Sideradougou area (south of Bobo Dioulasso, Burkina Faso) in order to identify transmission factors of African trypanosomosis. A total of 3600 tsetse flies (Glossina tachinoides, Glossina palpalis gambiensis) were captured along 120 km of linear gallery forest and half of them were dissected. PCR analysis was undertaken on parasitologically positive flies (161 G. tachinoides, 92 G. palpalis gambiensis) to characterize the different trypanosomes. All the results were integrated in a GIS (Geographical Information System). Spatial repartition of the characterized trypanosomes enabled to recognize different areas with specific patterns of infection. Relations with environmental factors are discussed.
Detection of Theileria lestoquardi (hirci) in Ticks, Sheep, and Goats Using the Polymerase Chain Reaction a
Authors: KIRVAR EROL , ILHAN TULIN , KATZER FRANK , WILKIE GWEN , HOOSHMAND‐RAD PARVIZ , BROWN DUNCAN
Published: February 2006

ABSTRACT: Theileria lestoquardi (=T. hirci) is a protozoan parasite of sheep and goats that is morphologically and biologically similar to T. annulata, the causative agent of bovine tropical theileriosis. Both parasites are transmitted by ixodid ticks of the genus Hyalomma. However, because of their morphological similarity, they cannot be distinguished in the salivary glands of infected ticks by traditional staining methods such as Feulgen or Methyl green‐pyronin. Thus a need has arisen for sensitive and specific diagnostic tests that will distinguish between the two species in the vector tick, allowing the epidemiology of both diseases to be clearly defined. A contribution to this has been the development of a polymerase chain reaction using specific primers which amplify, only in T. lestoquardi‐infected ticks, a 785 bp fragment of the gene that codes for a 30 kD merozoite surface protein. The sensitivity of this test and its application to the detection of T. lestoquardi in infected H. anatolicum anatolicum ticks, in the blood of three species of domestic ruminants and in cell cultures established in mononuclear cells of sheep and goats is also discussed.
A PCR‐based Field Evaluation of Theileria Infections in Cattle and Ticks in Kenya a
Authors: WATT D. , KIARA H. , SPARAGANO O. A. E.
Published: February 2006

ABSTRACT: Theileria parva is a hemoprotozoan parasite responsible for causing East Coast fever in east and central Africa. The vaccine currently available is an “infection and treatment” procedure which involves the injection of live sporozoites followed by drug therapy to prevent clinical illness. Before introducing potentially new strains of parasite into an area, however, it is crucial to check the disease situation in the field first. We looked at three different areas in Kenya: Limuru in which many cattle have already been vaccinated and Kitale and Kakamega which so far have not been vaccinated. Genus and species specific primers were used to test for the presence of Theileria species in blood and tick samples collected from the three areas. Limuru showed a cattle and tick infection prevalence of 27% and 2.3% respectively with T. parva. Kitale showed a cattle and tick infection prevalence of 100% and 14.2% respectively while Kakamega showed 100% and 0% respectively. Reasons for variations between areas involving vaccination status and epidemiological data are discussed.
Selection for Antigenic Diversity of Tams1, the Major Merozoite Antigen of Theileria annulataa
Authors: KATZER F. , MCKELLAR S. , BEN MILED L. , D'OLIVEIRA C. , SHIELS B.
Published: February 2006

ABSTRACT: Tams1, the major merozoite/piroplasm surface antigen of Theileria annulata has the potential to be a component of a diagnostic ELISA test and be included in a recombinant subunit vaccine. However, the observation that this antigen displays diversity could constrain these applications. In this paper we have extensively characterized Tams1 diversity at the DNA level, using a PCR/sequencing strategy. Up to 44 alleles have been cloned and sequenced. The comparison of these alleles has identified regions of sequence conservation, variability and hyper‐variability. Computer analysis of these alleles has indicated that positive selection may operate on certain regions of Tams1. Expression and Western blot analysis of selected alleles has indicated that sequence diversity is reflected in altered antigenicity and a continuum of relatedness and antibody cross recognition may exist. The possible function of the sequence conservation and polymorphism within Tams1 is discussed in relation to protein structure, host cell invasion and immune evasion.
PCR Amplification and Sequence of the p33 Piroplasm Surface Antigen Gene of a Theileria Species Isolated from Cattle in West Java, Indonesiaa
Authors: GOVAERTS M. M. , VOET M. , VOLCKAERT G. , GODDEERIS B. M.
Published: February 2006

ABSTRACT: Oriental theileriosis, a parasitic disease of cattle caused by protozoa of the Theileria orientalis/sergenti/buffeli group, has been reported in Indonesia but its causal agent had not yet been characterized. This study was carried out to isolate and characterize the parasite through comparison of its p33 piroplasm surface antigen gene sequence, with known p32 sequences of T. sergenti and T. buffeli isolates. A Theileria spp. isolate was collected from an Ongole cow in Jonggol, West‐Java, and transferred into a splenectomized calf for antigen production. Piroplasms were extracted from erythrocytes by ammonium chloride‐lysis, separated from unlysed leukocytes and parasitic DNA was phenol‐extracted. Polymerase chain reaction (PCR) was carried out on genomic DNA with a pair of 20 bp primers showing consensus for the p32‐35 nucleotide sequence of 7 known T. orientalis/sergenti/buffeli isolates. An 875 bp fragment was amplified, and further sequenced on both strands by the dye‐labeled terminators method. It showed an 88% homology with the p33 nucleotide sequence of the Japanese T. sergenti Ikeda stock and a lesser homology with 6 other sequences of Australian T. buffeli or Japanese T. sergenti stocks. It was shown to share the presence of the Pst 1 and the absence of the HindIII restriction sites of the T. sergenti Ikeda stock and of one Australian T. buffeli stock, respectively. In conclusion, the affiliation to and the relative position of this Indonesian isolate within the T. orientalis/sergenti/buffeli group has been elucidated.
A Stage‐specific, Parasite‐induced, “Window” of in Vivo Interferon‐γ Production Is Associated with Pathogenesis in Theileria annulata Infection
Authors: CAMPBELL J.D. M. , NICHANI A. K. , BROWN D. J. , GLASS E. J. , SPOONER R. L.
Published: February 2006

ABSTRACT: The tick‐borne protozoan parasite Theileria annulata causes tropical theileriosis, a severe leukoproliferative disease of cattle, which naive susceptible animals fail to control. The parasite infects and transforms macrophages, developing in the local draining lymph node. IFNγ has been shown to block parasite development in newly infected cells, and inhibits the growth of fully differentiated macroschizont stage‐infected cells in vitro. However, the parasite has been found to specifically induce IFNγ production by T cells and appears to flourish in the face of this T cell‐derived response in vivo. Here we show that the production of IFNγin vivo is tightly controlled by the parasite. Induction of cytokine production by T cells is not initiated until the parasite has developed beyond the IFNγ sensitive trophozoite stage. Cytokine production is kept high as infected macrophages develop, and IFNγ appears to play an active role in maintaining the growth of these cells. Once the infection is fully established, IFNγ is down regulated, avoiding potential inhibitory effects. Thus by controlling T cell IFNγ production, the parasite induces a “window” of cytokine expression which promotes its own growth, but avoids potential inhibitory effects of the cytokine.
Babesia bovis Immunity: In Vitro and in Vivo Evidence for IL‐10 Regulation of IFN‐γ and iNOSa
Authors: GOFF W. L. , JOHNSON W. C. , CLUFF C. W.
Published: February 2006

ABSTRACT: IL‐10 has been shown to have profound immunoregulatory attributes and in the bovine appears to downregulate both Th1‐ and Th2‐like responses. Using RT‐PCR, we demonstrate IL‐10 in vitro down‐regulation of mRNA expression of iNOS, the cytokines involved in nitric oxide signal transduction initiation (IFN‐γ and TNF‐α), and other mononuclear phagocyte associate cytokines. In addition, using RT‐PCR with peripheral blood leukocytes and spleen leukocytes, the Griess reaction, and a killing assay, we provide evidence for the importance of iNOS in a successful immune response to B. bovis infection and for high and persistent IL‐10 mRNA expression when the immune response is unsuccessful. We also provide evidence that antibody developed early after an initial infection appears to lack protective attributes (neutralizing and opsonic). Together, the data suggests that IL‐10 and IFN‐γ are critical molecules involved in the response to this intraerythrocytic protozoan infection.
Drug Sensitivity of Trypanosoma evansi and the Use of Immunoassays in Diagnosing Infections with T. evansi in Buffaloes in Vietnama
Authors: MY LE NGOC , WUYTS N. , LUCKINS A. G. , DUNG NGUYEN ANH , THANH NGUYEN THI GIANG
Published: February 2006

ABSTRACT: The biological characteristics of isolates of T.evansi collected from buffalo in different provinces in North Vietnam was determined in terms of their sensitivity to drugs currently used in the treatment of trypanosomosis. Five isolates were collected from buffalo, cloned and then tested against Trypamidium, Samorine, Naganol and Veriben. All isolates were sensitive to Naganol and Veriben. An isolate from a buffalo in Ha bac province (Hb1) was the least sensitive with trypamidium at a CD80 > 128mg/kg, more than 8 times the CD 100 of the remining isolates (16mg/kg). An antigen‐detection enzyme immunoassay (Ag‐ELISA) based on a T.evansi‐specific monoclonal antibody was evaluated for its ability to detect infections with T.evansi in buffalo. The sensitivity of the Ag‐ELISA was 63% and the specificity 75%. The positive predictive value of this assay was too low to allow identification of individual infected animals on the results of a single test in the districts investigated. For definitive diagnosis, a serial testing protocol was used, where a more specific test, the card agglutination test (CATT) was used initially and any positive samples was then checked by the Ag‐ELISA.
Studies on Host Resistance to Tick Infestations among Trypanotolerant Bos indicus Cattle Breeds in East Africaa
Authors: MWANGI E. K. , STEVENSON P. , NDUNG'U J. M. , STEAR M. J. , REID S.W. J. , GETTINBY G. , MURRAY M.
Published: February 2006

ABSTRACT: Recent epidemiological studies carried out in East Africa have indicated that some Bos indicus cattle breeds such as the Orma Boran and Maasai Zebu have a degree of trypanotolerance worth exploitation by their introduction into trypanosomosis endemic areas where other cattle breeds cannot survive. However, in most areas of East Africa, trypanosomosis, ticks, and tick‐borne diseases occur together. It is therefore important to obtain information on the susceptibility of these breeds to tick infestation and tick‐borne diseases. This study was therefore designed to determine the susceptibility of these cattle breeds to tick infestations. They were compared with the Galana Boran (trypanosusceptible) and the Friesian (susceptible to tick infestations, tick‐borne diseases, and trypanosomosis). The four breeds of cattle were exposed to natural tick challenge for a period of seven months and whole body weekly tick counts were done on each animal. Significant differences to tick infestations among the four breeds were observed. For both Rhipicephalus appendiculatus and Boophilus decoloratus, susceptibility to infestation increased in the order, Maasai Zebu, Orma Boran, Galana Boran and Friesian.

The results generated by this pilot study so far suggest that variation in susceptibility to tick infestations exists among the four breeds. The Orma Boran and Maasai Zebu showed greater resistance to tick‐infestations than the Galana Boran and Friesian. This suggests that utilization of these trypanotolerant cattle breeds could be feasible even in the face of tick challenge and should therefore be considered when planning integrated trypanosomosis and tick control strategies.
Bovine Babesiosis: Seroprevalence and Ticks Associated with Cattle from Two Different Regions of Moroccoa
Authors: SAHIBI H. , RHALEM AB. , BERRAG B. , GOFF W. L.
Published: February 2006

ABSTRACT: A total of 475 bovine sera collected in 1995‐1996 from 10 areas belonging to two different bioclimatic strata were tested for antibody activity to Babesia bigemina and Babesia bovis using indirect immunofluorescence (IIF). In the Gharb, the B. bovis seroprevalence was 21.7% and for B. bigemina, 10.8%. The infection rate for either or both species as determined microscopically with Giemsa‐stained blood films was 18.9%. The Tiflet area was considered an endemic focus, and the seroprevalence was 42.2% for B. bovis and 40% for B. bigemina. The infection rate by stained blood film microscopy was 66.6%. In the Haouz region, only B. bovis was found, and the seroprevalence was 10.1% with 9.4% microscopically positive blood films. More than 80% of the cattle surveyed were infested by ticks and the mean infestation rate was 36 ticks per animal and 21 ticks per animal in the Gharb and Haouz, respectively. Six species were identified. Hyalomma marginatum, Hyalomma detritum, Hyalomma anatolicum Rhipicephalus bursa, Rhipicephalus sanguineous and Boophilus annulatus. Boophilus annulatus was found in both regions with high prevalence in the Gharb (31.3%). No further correlation was made between the identified species as vectors and the presence of B. bovis and B. bigemina in these areas.
Different Vaccine Strategies Used to Protect against Theileria annulataa
Authors: BOULTER N. R. , BROWN C.G. D. , KIRVAR E. , GLASS E. , CAMPBELL J. , MORZARIA S. , NENE V. , MUSOKE A. , D'OLIVEIRA C. , GUBBELS M. J. , JONGEJAN F. , HALL F. R.
Published: February 2006

ABSTRACT: SPAG‐1, a sporozoite surface antigen of T. annulata, has previously been shown to elicit partial protection when used, as an hepatitis B core antigen fusion, to immunize cattle. The objective of this study was to try and improve the protective capacity of this antigen by enlisting different vaccine strategies. Cattle were immunized with SPAG‐1, as a fusion protein with a His6 tag, either incorporated into ISCOMs, with or without the merozoite antigens TAMS 1‐1 and 1‐2, or with RWL as adjuvant three times at monthly intervals. Another group of cattle were immunized with p67, the T. parva sporozoite antigen, in RWL to assess whether any cross‐protection could be induced. The animals were then challenged with an estimated LD50 of T. annulata sporozoites, and their ability to resist the infection was investigated. Serum responses and T‐cell proliferative responses were analyzed throughout the trial. Post‐challenge analyses included lymph node biopsies and blood smears to check for the presence of parasites, routine hematological parameters, and observation for clinical manifestations of the disease. The results of this trial will be discussed.
Evaluation of Anaplasma marginale from Tick Cell Culture as an Immunogen for Cattle a
Authors: BLOUIN EDMOUR F. , SALIKI JEREMIAH T. , KOCAN KATHERINE M. , RODGERS SANDY J.
Published: February 2006

ABSTRACT: Anaplasma marginale has been propagated and continuously passaged in an Ixodes scapularis cell line. Anaplasma development was characterized and cultures with a high density of rickettsiae were harvested at a predictable rate. Culture‐derived A. marginale (CAM) remained infective for cattle and was used effectively as antigen in diagnostic tests with the sensitivity to identify bovine carriers of A. marginale. This study presents results of an initial trial using the CAM as an immunogen for cattle. CAM was mechanically disrupted, frozen at −70°C, and inactivated with β‐propiolactone. Two intact yearling cattle were immunized with CAM and Freund's adjuvant, receiving 4 subcutaneous injections at 3‐4 week intervals. Two control yearling cattle received adjuvant and PBS. Serum samples were evaluated by competitive ELISA (C‐ELISA) using CAM as antigen and the standard complement fixation test (CFT). All cattle were subsequently challenged with A. marginale‐infected blood from a carrier cow. An additional intact calf was inoculated with live CAM from the same passage and screened by C‐ELISA and CFT. Sera collected from immunized cattle were negative or suspicious by CFT throughout the immunization study. The same sera were strongly positive by C‐ELISA two weeks after the first injection and throughout the study. All cattle became infected following challenge‐exposure with blood, but immunized cattle exhibited longer prepatent periods as well as lower parasitemias and percent reduction of packed cell volumes as compared with the controls. The calf receiving live CAM became infected and underwent a mild clinical reaction with positive C‐ELISA and CFT results and did not become clinically ill following blood challenge. This preliminary study suggests that the CAM antigen is highly immunogenic in cattle. Furthermore, the CFT did not identify immunized animals whereas the C‐ELISA (using CAM) was highly sensitive for detection of both immunized and infected animals.
Validation and Comparison of Three Enzyme‐linked Immunosorbent Assays for the Detection of Antibodies to Cowdria ruminantium Infection a
Authors: MONDRY R. , MARTINEZ D. , CAMUS E. , LIEBISCH A. , KATZ J. B. , DEWALD R. , VAN VLIET A. H.M. , JONGEJAN F.
Published: February 2006

ABSTRACT: Serological tests for Cowdria ruminantium infection have been hampered by low specificity. Here, an indirect ELISA based on purified antigen, a competitive ELISA using a recombinant major antigenic protein (MAP‐1) and an indirect ELISA based on the MAP‐1B region of the recombinant MAP‐1 were compared. The tests were validated using 3000 sera of ruminants from 14 islands of the Lesser Antilles as well as sequential serum samples from 10 cattle, 17 goats and 10 sheep vaccinated with inactivated C. ruminantium in ISA 50 adjuvant and from 14 goats infected with a virulent culture supernatant. All tests detected significantly higher percentages of positives on Antigua, Guadeloupe and Marie‐Galante, where C. ruminantium had been isolated before. Overall specificity calculated with sera from the other 11 heartwater‐free islands was 98.1%, 98.5%, and 99.4% for the ELISA based on crude antigen, recombinant MAP‐1 and MAP‐1B, respectively. Sensitivities observed with sequential serum samples were similar for all tests. Tests based on recombinant antigens, especially the MAP‐1B, showed improved specificity, suggesting their use for epidemiological studies in regions where the distribution of cowdriosis is unknown. In addition, the competitive ELISA is useful for studies in wildlife for which species‐specific conjugates do not exist.
The CARICOM/FAO/IICA Caribbean Amblyomma Programa
Authors: PEGRAM R. G. , DE CASTRO J. J. , WILSON D. D.
Published: February 2006

ABSTRACT: The objective of the Caribbean Amblyomma Program is to eradicate the tropical bont tick (TBT), Amblyomma variegatum, from the Caribbean. Field activities directed to eradication of the TBT were initiated in May 1995 commencing in northern Caribbean islands. Plans have been finalized for the remaining islands to the south to start eradication activities in early 1997. The components of the program include tick control and surveillance, adaptive research, training, communications, and extension. Despite uncertain financial support, substantial progress has been made so far with strong participation by farmers and livestock owners who have been made responsible for the compulsory treatment of all ruminant livestock.
Molecular Basis of Intestinal Adaptation: The Role of the Insulin‐like Growth Factor System
Authors: LUND P. KAY
Published: February 2006

ABSTRACT: Ongoing and future approaches to the cellular and molecular actions of insulin‐like growth factor I (IGF‐I) and growth hormone (GH) in intestinal adaptation are reviewed. This is highly relevant to understanding the benefits and risks associated with increasing use of GH and IGF‐I in patients with short bowel syndrome or other bowel diseases. As other growth factors share some of the properties of IGF‐I including local expression in bowel, activation of signaling pathways common to other growth factors or cytokines, and modulation of action by growth factor‐binding proteins or secreted receptor isoforms. The general issues and approaches outlined for IGF‐I should, therefore, serve as a model for studies aimed at understanding the cellular and molecular mechanisms of action of other growth factors that are implicated in intestinal adaptation.
Interaction of Microorganisms, Epithelium, and Lymphoid Cells of the Mucosa‐Associated Lymphoid Tissue
Authors: HAMZAOUI NADIM , PRINGAULT ERIC
Published: February 2006

ABSTRACT:Differentiation of specific epithelial cell lineages during development, as well as epithelial plasticity in response to heterologous cell‐to‐cell cross talk during adult life, accounts for the large variety of functions which are performed by the mucosal surfaces found in the human body. Among its functions, the digestive mucosa is able to sample antigens and microorganisms through M cells of Peyer's patches follicle‐associated epithelium, in order to trigger the development of either tolerance or immune responses. At least in the gut, M‐cell formation is immunoregulated. Close contact between immune cells and intestinal epithelium modifies the permeability of the epithelial barrier by inducing the conversion of enterocytes into M cells, offering at the same time an opportunistic way of invasion for pathogens. These lympho‐epithelial interactions triggering M‐cell formation have now been modeled in culture.
HIV/SIV Enteropathy
Authors: ZEITZ M. , ULLRICH R. , SCHNEIDER T. , KEWENIG S. , HOHLOCH K. , RIECKEN E. O.
Published: February 2006

ABSTRACT: Evidence is increasing that HIV/SIV‐induced changes in the highly differentiated gut‐associated immune system play a central role in the pathogenesis of gastrointestinal manifestations in HIV/SIV infection. It has been shown in both humans infected with HIV and in nonhuman primates infected with SIV that a rapid, very early, and more pronounced loss of CD4+ T‐cells occurs in the mucosa in comparison to the peripheral blood. The loss of this important regulatory T‐cell subset might explain mucosal immunodeficiency with the consequence of opportunistic mucosal infections. In addition, there is evidence that small intestinal damage occurs independently of secondary infections (HIV/SIV enteropathy). In late‐stage human disease, HIV enteropathy is characterized by villous atrophy with hyporegeneration and dysmaturation of intestinal epithelial cells. In SIV infection of macaques, villous atrophy is a very early event; however, it is accompanied by crypt cell hyperproliferation. Early‐ and late‐stage enteropathy in immunodeficiency virus infection may represent two types of immunologically mediated mucosal transformation in which the number and state of activation of regulatory T cells determine whether hypo‐ or hyperproliferative villous atrophy occurs.
Cytokine Gene Transcription By NF‐κB Family Members in Patients with Inflammatory Bowel Disease
Authors: NEURATH MARKUS F. , FUSS IVAN , SCHÜRMANN GUIDO , PETTERSSON SVEN , ARNOLD KARL , MÜLLER‐LOBECK HELMUT , STROBER WARREN , HERFARTH CHRISTIAN , ZUM BÜSCHENFELDE KARL‐HERMANN MEYER
Published: February 2006

ABSTRACT: We examined the expression of the transcription factor NF‐κB, a nuclear trans‐acting factor known to play a key role in cytokine gene regulation, in patients with inflammatory bowel disease (IBD). It was found that LP macrophages in Crohn's disease (CD) and ulcerative colitis (UC) display high levels of NF‐κB DNA‐binding activity accompanied by an increased production of interleukin (IL)‐1, IL‐6, and tumor necrosis factor (TNF)α. Western blot studies showed an increased expression of the p50 and c‐rel subunits of NF‐κB; however, the most striking finding was an increased expression level of NF‐κB p65 in patients with CD and UC. Selective downregulation of p65 in IBD macrophages by a specific antisense phosphorothioate oligonucleotide was sufficient to considerably reduce production of proinflammatory cytokines. These results demonstrate a characteristic increase of NF‐κB binding levels in patients with IBD. The data suggest that antisense DNA targeting NF‐κB p65 can be used as a novel molecular approach for the treatment of patients with IBD.
Solution Structure Comparison of the VIP/PACAP Family of Peptides by NMR Spectroscopy
Authors: WRAY VICTOR , NOKIHARA KIYOSHI , NARUSE SATORU
Published: February 2006

Abstract: The current status of structural studies of the VIP/PACAP family of peptides in solution by NMR spectroscopy is briefly reviewed. The structural elucidation methodology is described with examples from recent work and finally general structural conclusions are drawn from data from the now extensive literature.
Induction of Type I PACAP Receptor Expression by the New Zinc Finger Protein Zac1 and p53
Authors: HOFFMANN ANKE , CIANI ELISABETTA , HOUSSAMI SOUHEIR , BRABET PHILIPPE , JOURNOT LAURENT , SPENGLER DIETMAR
Published: February 2006

Abstract: We reported recently the cloning of the type I PACAP receptor by a functional expression cloning technique. Unexpectedly, we observed additional PACAP‐positive pools that turned out to encode the wild‐type form of the tumor suppressor gene p53 and the novel zinc finger protein Zac1, which regulates apoptosis and cell cycle arrest. 1 Both Zac1 and p53 caused, under transient or stably regulated expression, induction of the type I PACAP receptor by transcriptional mechanisms. Transactivation of the type I PACAP receptor gene by Zac1 and p53 points to a subtle balance between death promoting and protective mechanisms. The control of these processes is central to various physiological conditions ranging from development to senescence, whereas dysregulation may lead to overt pathological outcomes, notably cancer, immune deficiency syndromes, and neurodegenerative disorders.
PACAP Protects Hippocampal Neurons against Apoptosis: Involvement of JNK/SAPK Signaling Pathwaya
Authors: SHIODA SEIJI , OZAWA HIROSHI , DOHI KENJI , MIZUSHIMA HIDEKATSU , MATSUMOTO KIYOSHI , NAKAJO SHIGEO , TAKAKI ATSUSHI , ZHOU CHENG JI , NAKAI YASUMITSU , ARIMURA AKIRA
Published: February 2006

Abstract: We have demonstrated that the ischemia‐induced apoptosis of neurons in the CA1 region of the rat hippocampus was prevented by either intracerebroventricular or intravenous infusion of pituitary adenylate cyclase‐activating polypeptide (PACAP). However, the molecular mechanisms underlying the anti‐apoptotic effect of PACAP remain to be determined. Within 3–6 h after ischemia, the activities of members of the mitogen‐activated protein (MAP) kinase family, including extracellular signal‐regulated kinase (ERK), Jun N‐terminal kinase (JNK)/stress‐activated protein kinase (SAPK), and p38 were increased in the hippocampus. The ischemic stress had a potent influence on the MAP kinase family, especially on JNK/SAPK. PACAP inhibited the activation of JNK/SAPK after ischemic stress. Secretion of interleukin‐6 (IL‐6) into the cerebrospinal fluid was intensely stimulated after PACAP infusion. IL‐6 inhibited the activation of JNK/SAPK, while it activated ERK. These observations suggest that PACAP and IL‐6 act to inhibit the JNK/SAPK signaling pathway, thereby protecting neurons against apoptosis.
Stimulatory Transducing Systems in Pancreatic Islet Cellsa
Authors: EMAMI SHAHIN , REGNAULD KARINE , FERRAND NATHALIE , ASTESANO ANY , PESSAH MARCIA , PHAN HUAN , BOISSARD CLAUDINE , GAREL JEAN‐MICHEL , ROSSELIN GABRIEL
Published: February 2006

Abstract: We have determined the cellular distribution of different alpha subtypes of G proteins and adenylyl cyclase (AC) isoforms in endocrine, exocrine, and established pancreatic cell lines. VIP, PACAP, and tGLP‐1 receptor proteins are expressed to varying extents in A and B cells, whereas the expression of Gα subunits is cell specific. Thus, Golfα is detected in normal rodent B cells and immortalized pancreatic B cell lines, whereas Gsα is more ubiquitously expressed. The cellular density of AC isoforms labeling (I, II, III, IV, V/VI) is also islet cell‐specific and their distribution is age‐ and species‐dependent. The identification of numerous signaling molecule subtypes, together with the discovery of their specific subcellular distribution, will help the functional characterization of their intraregulatory pathways, leading to the extrusion of insulin or glucagon secretory granules, and those leading to differentiation and apoptosis of islet cells.
A Critical View of the Methods for Characterization of the VIP/PACAP Receptor Subclassesa
Authors: ROBBERECHT PATRICK , WAELBROECK MAGALI
Published: February 2006

Abstract: The binding properties of the three cloned VIP/PACAP receptors and their coupling to G proteins and effectors can be studied in cells expressing each recombinant protein. The data obtained in these models must be critically evaluated:the expression of a high receptor density may reveal irrelevant receptors states and coupling to non‐cognate G protein, and entail a marked amplification of the response as well as distortions in the selectivity profile of full and partial agonists. These models are, however, of great interest in the design of selective agonists and antagonists for each receptor subtype. The availability of selective ligands will facilitate the identification of the receptor subtype responsible for PACAP and VIP actions in cells and tissues.
VIP Neurotrophism in the Central Nervous System: Multiple Effectors and Identification of a Femtomolar‐Acting Neuroprotective Peptide
Authors: BRENNEMAN DOUGLAS E. , GLAZNER GORDON , HILL JOANNA M. , HAUSER JANET , DAVIDSON ARIANE , GOZES ILLANA
Published: February 2006

Abstract: Vasoactive intestinal peptide has neurotrophic and growth‐regulating properties. As in the case of many neurotrophic molecules, VIP also has neuroprotective properties, including the prevention of cell death associated with excitotoxicity (NMDA), beta‐amyloid peptide, and gp120, the neurotoxic envelope protein from the human immunodeficiency virus. The neurotrophic and neuroprotective properties are mediated in part through the action of glial‐derived substances released by VIP. These substance include cytokines, pro tease nexin I, and ADNF, a novel neuroprotective protein with structural similarities to heat‐shock protein 60. Antiserum against ADNF produced neu ronal cell death and an increase in apoptotic neurons in cell culture. A 14 amino acid peptide (ADNF‐14) derived from ADNF has been discovered that mimics the survival‐promoting action of the parent protein. These studies support the conclusion that VIP, PACAP, and associated molecules are both important regulators of neurodevelopment and strong candidates for therapeutic development for the treatment of neurodegenerative disease.
Maxadilan Is a Specific Agonist and Its Deleted Peptide (M65) Is a Specific Antagonist for PACAP Type 1 Receptor
Authors: UCHIDA D. , TATSUNO I. , TANAKA T. , HIRAI A. , SAITO Y. , MORO O. , TAJIMA M.
Published: February 2006

Abstract: Maxadilan is a potent vasodilator peptide isolated from salivary glands extracts of the hematophagous sand fly. Recently, it was demonstrated that maxadilan binds to PACAP receptor type 1 in mammals, although maxadilan has no significant amino acid sequence homology with PACAP. In the present study, we demonstrated that maxadilan is a specific agonist of PACAP type 1 receptor (PACAP/VIP receptor 1; PVR1) as determined by the binding assay of [125I]PACAP27 and cAMP accumulation using CHO cells stably expressing PVR1, VIP1 receptor (PVR2), and VIP2 receptor (PVR3), and that the deleted peptide (#25‐41) of maxadilan (termed as M65) is a specific antagonist of PVR1. In addition, maxadilan shares the binding sites for PACAP and stimulates cAMP in cultured rat cortical neurons. VIP stimulates cAMP accumulation probably through the binding to PVR1 since M65 blocks the VIP‐induced cAMP accumulation in cultured rat cortical neurons.
Importance of Conserved Cysteines in the Extracellular Loops of Human PACAP/VIP1 Receptor for Ligand Binding and Stimulation of cAMP Productiona
Authors: KNUDSEN SANNE MØLLER , TAMS JEPPE WEGENER , WULFF BIRGITTE S. , FAHRENKRUG JAN
Published: February 2006

Abstract: The importance of two highly conserved cysteines in the human pituitary adenylate cyclase activating polypeptide (PACAP)/vasoactive intestinal peptide 1 (VIP1) receptor was examined. Using site‐directed mutagenesis, each Cys residue was converted into Ala or Ser. The mutant and wildtype genes were transfected into HEK293 cells and tested for the ability to bind VIP and to activate cAMP production. Cys215Ala/Ser and Cys285Ala/Ser showed at least a tenfold decrease in binding affinity and receptor potency when compared to the wildtype. In contradiction to the wildtype receptor, both mutations were insensitive to dithiothreitol (DTT). The results indicate the existence of a disulfide bond between Cys215 and Cys285, which is important for stabilizing the receptor in the correct conformation for ligand binding and activation.
Multiple Actions of a Hybrid PACAP Antagonist: Neuronal Cell Killing and Inhibition of Sperm Motilitya
Authors: GOZES ILLANA , PERL ORLY , ZAMOSTIANO RACHEL , RUBINRAUT SARA , FRIDKIN MATI , SHOCHAT LEAH , LEWIN LAWRENCE M.
Published: February 2006

Abstract: Pituitary stimulating adenylate cyclase (PACAP) is a major regulatory peptide with two active molecular forms: PACAP‐27 and PACAP‐38. Both molecular forms promote neuronal survival and protect against neurotoxicity. Based on our previous hybrid peptide strategy in designing vasoactive intestinal peptide (VIP) antagonists, novel PACAP analogues were synthesized (neurotensin6‐11 PACAP7‐27 and neurotensin6‐11 PACAP7‐38). In addition to the hybrid modification, the methionine in position 17 was replaced by norleucine (Nle). Treatment of rat cerebral cortical cultures for five days with the putative PACAP antagonists (1 nM) resulted in a 35‐45% reduction in neuronal cell counts as compared to controls. Neuronal cell death was already obtained at picomolar concentrations for the neurotensin6‐11PACAP7‐27 antagonist with 70% death at 10−8 M. Co‐administration of the PACAP hybrid analogue with picomolar amounts of PACAP‐27 or Nle17‐PACAP‐27 attenuated the reduction in neuronal cell counts. While the protective effects of both analogues exhibited a peak at 1 pM concentrations, the Nle‐containing agonist displayed a broader range of active concentrations (10−12 M‐10−9 M)

The putative PACAP antagonist also inhibited sperm motility (golden hamster) in a dose‐dependent manner as assessed in vitro. Complete inhibition was observed at 10 μM, suggesting a role for PACAP in sperm motility and sexual function. Thus, previous findings of a large number of PACAP and PACAP receptors in the nervous system and the reproductive system are now correlated with a function in neuronal survival and sperm motility. The structure‐activity studies suggest that the methionine in position 17 and the first six amino acids are important in the determination of PACAP activity, knowledge that may facilitate PACAP‐based drug design.
VIP and Breast Cancer
Authors: MOODY T. W. , LEYTON J. , GOZES I. , LANG L. , ECKELMAN W. C.
Published: February 2006

Abstract: VIP1 receptors are present In breast cancer cells. VIP elevates the cAMP and stimulates nuclear oncogene expression In MCF‐7 cells. VIPhybrid is a VIP receptor antagonist that Inhibits breast cancer proliferation. A VIP analog has been developed for imagIng breast tumors. Therefore VIP1 receptors may be utilized for the early detection and treatment of breast cancer.
Coordinated Role of Vasoactive Intestinal Peptide and Nitric Oxide in Cardioprotectiona
Authors: DAS DIPAK K. , KALFIN RENI , MAULIK NILANJANA , ENGELMAN RICHARD M.
Published: February 2006

Abstract: The present study sought to examine the interrelationship between nitric oxide (NO) and vasoactive intestinal peptide (VIP) in myocardial protection. Isolated rat hearts were perfused for 15 min with buffer only (Group I); 0.3 μM VIP (Group II); 3 μM L‐arginine (a precursor of NO) (Group III); VIP and aminoguanidine (iNOS blocker) (Group IV); or L‐arginine plus VIP 10‐28 (VIP inhibitor) (Group V). Each heart was then made globally ischemic for 30 min followed by 2 h reperfusion. Both VIP and NO were found to provide cardioprotection during ischemia and reperfusion. However, the beneficial effects of VIP and NO were reduced by inhibition of NO and VIP, respectively, suggesting that cardioprotection by VIP is modulated by NO and vice versa. The results of this study suggested a coordinated regulation by cardioprotection by NO and VIP.
Is There Appetite after GLP‐1 and PACAP?
Authors: CHRISTOPHE JEAN
Published: February 2006

Abstract: Anitobesity drugs must increase the sensitivity of the hypothalamic satiety center towards leptin and antagonize the synthesis and action of NPY. The array of pharmacologic tools available is vast and presently ineffective. Among peptide analogs considered for evaluation [NPY‐5 antagonists and CCK‐A, bombesin, amylin and melanocyte‐stimulating hormone‐4 (or melanin‐concentrating hormone?) agonists], is there a place for GLP‐1 and PACAP? GLP‐1 receptors present in ARC, PVN, VMN, and SON are the target for both central and blood‐borne GLP‐1 in those hypothalamic neurons endowed with GLUT‐2 and glucokinase. GLP‐1, hypersecreted by L‐cells after a meal, is a potent insulinotropic agent and, together with glucose, reduces food intake and induces c‐fos in the ARC. PACAP is present in the ARC, PVN, and SCH, and its hypothalamic type I receptor elevates cAMP and inositol triphosphate in the PVN, where it may perhaps antagonize NPY‐induced food intake and hyperinsulinemia. However, irrelevant neuroendocrine, autonomic, and circadian functions are also activated by this peptide, making it a less than ideal base on which to build an obesity treatment.
From Quasars to ExtraordinaryN‐body Problems
Authors: LYNDEN‐BELL D.
Published: February 2006

ABSTRACT:We outline reasoning that led to the current theory of quasars and look at George Contopoulos's place in the long history of theN‐body problem. Following Newton we find new exactly solubleN‐body problems with multibody forces and give a strange eternally pulsating system that in its other degrees of freedom reaches statistical equilibrium.
Negative Energy Modes and Gravitational Instability of Interpenetrating Fluids
Authors: CASTI A. R.R. , MORRISON P. J. , SPIEGEL E. A.
Published: February 2006

ABSTRACT: We study the longitudinal instabilities of two interpenetrating fluids interacting only through gravity. When one of the constituents is of relatively low density, it is possible to have a band of unstable wavenumbers well separated from those involved in the usual Jeans instability. If the initial streaming is large enough, and there is no linear instability, the indefinite sign of the free energy has the possible consequence of explosive interactions between positive and negative energy modes in the nonlinear regime. The effect of dissipation on the negative energy modes is also examined.
Invariants and Labels in Lie‐Poisson Systems
Authors: THIFFEAULT JEAN‐LUC , MORRISON P. J.
Published: February 2006

ABSTRACT: Reduction is a process that uses symmetry to lower the order of a Hamiltonian system. The new variables in the reduced picture are often not canonical: there are no clear variables representing positions and momenta, and the Poisson bracket obtained is not of the canonical type. Specifically, we give two examples that give rise to brackets of the noncanonical Lie‐Poisson form: the rigid body and the two‐dimensional ideal fluid. From these simple cases, we then use the semidirect product extension of algebras to describe more complex physical systems. The Casimir invariants in these systems are examined, and some are shown to be linked to the recovery of information about the configuration of the system. We discuss a case in which the extension is not a semidirect product, namely compressible reduced MHD, and find for this case that the Casimir invariants lend partial information about the configuration of the system.
N‐Body Simulations of Galaxies and Groups of Galaxies with the Marseille GRAPE Systems
Authors: ATHANASSOULA E.
Published: February 2006

ABSTRACT: I review the Marseille GRAPE systems and the N‐body simulations done with them. First I briefly describe the available hardware and software, their possibilities and their limitations. I then describe work done on interacting galaxies and groups of galaxies. This includes simulations of the formation of ring galaxies, simulations of bar destruction by a massive compact satellite, of merging in compact groups and of the formation of brightest members in clusters of galaxies.
Counterrotating Galaxies and Accretion Disks
Authors: LOVELACE R.V. E.
Published: February 2006

ABSTRACT:Theoretical interest in astrophysical disks with counterrotating components of stars and/or gas has been stimulated by recently discovered counterrotating spiral and S0 galaxies. A variety of physical processes can occur in counterrotating disks. We have shown that a strong two‐stream instability can occur for one armed (m= 1) tightly‐wrapped spiral waves between co and counterrotating stellar components and/or between a corotating stellar component and a counterrotating gaseous component. The instability of counterrotating stellar components has been clearly seen in computer simulations. The unstable two‐stream spiral waves can provide an effective viscosity for the gas causing its rapid accretion.

Accretion disks consisting of counterrotating gaseous components may exist with an intervening shear layer. Configurations of this type can arise from the accretion of newly supplied counterrotating gas onto an existing corotating gas disk. For example, the gas above the disk midplane can rotate with angular rate +Ω(r) while that well below has the same properties but rotates with rate −V(r). Using the Shakura‐Sunyaev alpha turbulence model, we find self‐similar solutions where a thin (relative to the full disk thickness) equatorial layer accretes very rapidly, essentially at free‐fall speed. This type of accretion flow has now been observed in hydrodynamic simulations.
Candidates for Abundance Gradients at Intermediate Red‐Shift Clusters
Authors: DUPKE RENATO A.
Published: February 2006

ABSTRACT: In this work I present evidence for the possible existence of central abundance enhancements in two clusters of galaxies at intermediate redshifts: Abell 1413 (z ∼ 0.14) and Abell 2390 (z ∼ 0.23). The results are based on ASCA (Advanced Satellite for Cosmolgy and Astrophysics) data reduction of x‐ray spatially resolved spectra. The Fe abundance for A1413 drops from 0.37 ± 0.08 (in the central 2 arcmin) to 0.20 ± 0.06 (in the outer 2‐6 arcmin), while in A2390 the very central abundance is 0.77 ± 0.45 (central arcmin) and drops to 0.12 ± 0.12 in the outer regions.
Scaling Regimes in the Distribution of Galaxies
Authors: MURANTE G. , PROVENZALE A. , SPIEGEL E. A. , THIEBERGER R.
Published: February 2006

ABSTRACT: If we treat the galaxies in published redshift catalogues as point sets, we may determine the generalized dimensions of these sets by standard means, outlined here. For galaxy separations up to about 5 Mpc, we find the dimensions of the CfA galaxy set to be about 1.2, with only a modest indication of multifractality. For larger scales, out to about 30 Mpc, there is also good scaling with a dimension of about 1.8. For even larger scales, the data seem too sparse to be conclusive, but we find that the dimension is climbing as the scales increase. We report simulations that suggest a rationalization of such measurements, namely that in the intermediate range the scaling behavior is dominated by flat structures (pancakes) and that the results on the smallest scales are a reflection of the formation of density singularities.