bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of habitat heterogeneity on the distribution of larval Pacific lamprey (Lampetra tridentata) at two spatial scales
Authors: Torgersen Christian E. , Close David A. 
Published: April 2004

Summary1. Spatial patterns in channel morphology and substratum composition at small (1–10 metres) and large scales (1–10 kilometres) were analysed to determine the influence of habitat heterogeneity on the distribution and abundance of larval lamprey.2. We used a nested sampling design and multiple logistic regression to evaluate spatial heterogeneity in the abundance of larval Pacific lamprey, Lampetra tridentata, and habitat in 30 sites (each composed of twelve 1‐m2 quadrat samples) distributed throughout a 55‐km section of the Middle Fork John Day River, OR, U.SA. Statistical models predicting the relative abundance of larvae both among sites (large scale) and among samples (small scale) were ranked using Akaike's Information Criterion (AIC) to identify the ‘best approximating’ models from a set of a priori candidate models determined from the literature on larval lamprey habitat associations.3. Stream habitat variables predicted patterns in larval abundance but played different roles at different spatial scales. The abundance of larvae at large scales was positively associated with water depth and open riparian canopy, whereas patchiness in larval occurrence at small scales was associated with low water velocity, channel‐unit morphology (pool habitats), and the availability of habitat suitable for burrowing.4. Habitat variables explained variation in larval abundance at large and small scales, but locational factors, such as longitudinal position (river km) and sample location within the channel unit, explained additional variation in the logistic regression model. The results emphasise the need for spatially explicit analysis, both in examining fish habitat relationships and in developing conservation plans for declining fish populations.
Restricted movement by mottled sculpin (pisces: cottidae) in a southern Appalachian stream
Authors: Petty J. Todd , Grossman Gary D. 
Published: April 2004

Summary1. We used direct observation and mark‐recapture techniques to quantify movements by mottled sculpins (Cottus bairdi) in a 1 km segment of Shope Fork in western North Carolina. Our objectives were to: (i) quantify the overall rate of sculpin movement, (ii) assess variation in movement among years, individuals, and sculpin size classes, (iii) relate movement to variation in stream flow and population size structure, and (iv) quantify relationships between movement and individual growth rates.2. Movements were very restricted: median and mean movement distances for all sculpin size classes over a 45 day period were 1.3 and 4.4 m respectively. Nevertheless, there was a high degree of intrapopulation and temporal variation in sculpin movement. Movement of juveniles increased with discharge and with the density of large adults. Movement by small and large adults was not influenced by stream flow, but large adults where more mobile when their own density was high. Finally, there were differences in the growth rates of mobile and sedentary sculpins. Mobile juveniles grew faster than sedentary individuals under conditions of low flow and high density of large adults, whereas adults exhibited the opposite pattern.3. Our results support the hypothesis that juvenile movement and growth is influenced by both intraspecific interactions with adults and stream flow. In contrast, adult movement appears to be influenced by competitive interactions among residents for suitable space. The relationship between movement and growth may provide a negative feedback mechanism regulating mottled sculpin populations in this system.
Possession of human leucocyte antigen DQ6 alleles and the rate of CD4 T‐cell decline in human immunodeficiency virus‐1 infection
Authors: Vyakarnam Annapurna , Sidebottom David , Murad Shahed , Underhill James A. , Easterbrook Philippa J. , Dalgleish Angus G. , Peakman Mark 
Published: April 2004

SummaryPolymorphism amongst the human leucocyte antigen (HLA) class II genes could influence antigen presentation and the ability to control human immunodeficiency virus (HIV)‐1 by modulating the virus specific CD4 immune response. To examine the effect of such polymorphisms on disease progression, we studied a cohort of 46 HIV‐1 infected long‐term non‐progressors (LTNPs), 87 intermediate progressors (IPs) and 26 rapid progressors. Kaplan–Meier survival analysis of all patients in the cohort on time to a CD4 count less than 350 cells/µl, showed a trend for a slower rate of CD4 decline in patients with, compared to those without, the DRB1*15‐DQB1*06 haplotype (hazard ratio (HR) 0·69, 95% CI 0·46–1·01, P = 0·06). A similar effect was not observed with the DRB1*13‐DQB1*06 haplotype (HR 1·18, 95% CI 0·75–1·88, P = 0·46), but was observed when DQB1*06 alleles were considered irrespective of their DR association (HR 0·74, 95% CI 0·52–1·05, P = 0·06). Major HLA‐DQ6 alleles encode aspartate (Asp) at position 57 on the DQβ chain, a phenotype associated with protection from other immune disorders. We therefore examined the frequency of all DQβ57 Asp+ alleles, but could not detect a significant effect on the rate of CD4 decline. To examine whether the genotype associated with slower CD4 decline was over‐represented in patients with a slow rate of disease progression, we conducted a categorical analysis of a subset of patients with an extended follow‐up of 14+years. We found a higher proportion of LTNPs at 14+ years possessed the DRB1*15‐DQB1*06 haplotype compared to IPs at 14+ years (38·46 versus 18·18%), though this difference did not reach statistical significance. When DQB1*06 alleles irrespective of their DR association were considered, the protective effect was greater (76·9% LTNPs versus 18·18% IPs, P = 0·04). Our results highlight the potential protective effect of HLA DQB1*06 alleles on the course of HIV disease.
Interferon‐γ activation of polymorphonuclear neutrophil function
Authors: Ellis Terri N. , Beaman Blaine L. 
Published: April 2004

SummaryAs current research illuminates the dynamic interplay between the innate and acquired immune responses, the interaction and communication between these two arms has yet to be fully investigated. Polymorphonuclear neutrophils (PMNs) and interferon‐γ (IFN‐γ) are known critical components of innate and acquired immunity, respectively. However, recent studies have demonstrated that these two components are not entirely isolated. Treatment of PMNs with IFN‐γ elicits a variety of responses depending on stimuli and environmental conditions. These responses include increased oxidative burst, differential gene expression, and induction of antigen presentation. Many of these functions have been overlooked in PMNs, which have long been classified as terminal phagocytic cells incapable of protein synthesis. As this review reports, the old definition of the PMN is in need of an update, as these cells have demonstrated their ability to mediate the transition between the innate and acquired immune responses.
CpG‐ODN‐stimulated dendritic cells act as a potent adjuvant for E7 protein delivery to induce antigen‐specific antitumour immunity in a HPV 16 E7‐associated animal tumour model
Authors: Kim Tai‐Gyu , Kim Chang‐Hyun , Won Eun Ha , Bae Su Mi , Ahn Woong‐Shick , Park Jae‐Bok , Sin Jeong‐Im 
Published: April 2004

SummaryWe previously reported that both E7 and CpG‐oligodeoxynucleotide (ODN) are required for protecting animals from human papillomavirus (HPV) 16 E7‐associated tumour challenge. Here we investigate dendritic cells (DC)‐based approach in this protection. In the study, we isolated bone marrow‐derived DC and stimulated DC with E7 and ODN. In vitro stimulation of DC with E7 plus ODN resulted in more production of interleukin‐12, as compared to that with E7 or ODN alone. Further injection with E7+ODN‐stimulated DC resulted in more significant tumour protection, as compared to stimulation with E7 or ODN alone. We further evaluated the levels of immune responses induced by DC stimulated with E7+ODN. We observed little enhancement of E7‐specific antibody and T helper cell proliferative responses by E7+ODN stimulation, as compared to E7 stimulation. However, there was some enhancement of interferon‐γ (IFN‐γ) production from CD4+ T cells and a more significant production of IFN‐γ from CD8+ T cells by E7+ODN stimulation, as compared to E7 stimulation alone. This was consistent with intracellular IFN‐γ staining levels of CD8+ T cells. Tumour protection further appeared to be mediated by CD8+ T cells, as determined by in vivo T‐cell depletion. Thus, these data suggest that upon ODN stimulation DC might function as a potent adjuvant for E7 protein delivery for induction of protective cellular immunity against HPV E7‐associated tumour challenge.
Identification, functional analysis and expression in a heterotopic heart transplant model of CXCL9 in the rat
Authors: Mitsuhashi Noboru , Kearns‐Jonker Mary , Wu Gordon D. , Bowdish Michael E. , Jin Yang‐Sun , Mencel Robert , Zahorsky‐Reeves Joanne , Fischer‐Lougheed Jacqueline , Weinberg Kenneth I. , Starnes Vaughn A. , Cramer Donald V. 
Published: April 2004

SummaryCXCR3 chemokines are of particular interest because of their potential involvement in a variety of inflammatory diseases, including the rejection of organ transplants. Although the rat is one of the most appropriate animals for using to study transplantation biology, the structural and functional characteristics of CXCL9 [monokine induced by interferon‐γ (Mig)] in this experimental model have not been described. Therefore, we recently conducted a series of experiments to identify and characterize the rat CXCL9 gene. Accordingly, we isolated rat CXCL9 cDNA and genomic DNA. The rat CXCL9 gene encodes a protein of 125 amino acids and spans a 3·5 kbp DNA segment containing four exons in the protein‐coding region. We then analysed mRNA expression in various tissues. Transcripts for the gene were found to be expressed at high levels in the lymph nodes and spleen. Then, to confirm the function of the identified gene, rat CXCL9 was transiently expressed in COS‐1 cells. Rat recombinant Mig displayed chemotactic properties and induced CXCR3 internalization in CD4+ T cells. Lastly, we analysed the expression of rat CXCL9 in a heterotopic heart allograft model. Both mRNA and protein levels of intragraft CXCL9 were significantly increased following transplantation of ACI to LEW hearts when compared with syngeneic controls. These findings indicate that rat CXCL9 has an in vivo role in the infiltration of CD4+ T cells in the transplanted graft.
Major histocompatibility complex class I‐restricted alloreactive CD4+ T cells
Authors: Boyle Louise H. , Goodall Jane C. , Gaston J. S. Hill 
Published: April 2004

SummaryAlthough it is well established that CD4+ T cells generally recognize major histocompatibility complex (MHC) class II molecules, MHC class I‐reactive CD4+ T cells have occasionally been reported. Here we describe the isolation and characterization of six MHC class I‐reactive CD4+ T‐cell lines, obtained by co‐culture of CD4+ peripheral blood T cells with the MHC class II‐negative, transporter associated with antigen processing (TAP)‐negative cell line, T2, transfected with human leucocyte antigen (HLA)‐B27. Responses were inhibited by the MHC class I‐specific monoclonal antibody (mAb), W6/32, demonstrating the direct recognition of MHC class I molecules. In four cases, the restriction element was positively identified as HLA‐A2, as responses by these clones were completely inhibited by MA2.1, an HLA‐A2‐specific mAb. Interestingly, three of the CD4+ T‐cell lines only responded to cells expressing HLA‐B27, irrespective of their restricting allele, implicating HLA‐B27 as a possible source of peptides presented by the stimulatory MHC class I alleles. In addition, these CD4+ MHC class I alloreactive T‐cell lines could recognize TAP‐deficient cells and therefore may have particular clinical relevance to situations where the expression of TAP molecules is decreased, such as viral infection and transformation of cells.
Functional characterization of human natural killer cells responding to Mycobacterium bovis bacille Calmette‐Guérin
Authors: Esin Semih , Batoni Giovanna , Pardini Manuela , Favilli Flavia , Bottai Daria , Maisetta Giuseppantonio , Florio Walter , Vanacore Renato , Wigzell Hans , Campa Mario 
Published: April 2004

SummaryThe kinetics of activation and induction of several effector functions of human natural killer (NK) cells in response to Mycobacterium bovis bacille Calmette‐Guérin (BCG) were investigated. Owing to the central role of monocytes/macrophages (MM) in the initiation and maintenance of the immune response to pathogens, two different experimental culture conditions were analysed. In the first, monocyte‐depleted nylon wool non‐adherent (NW) cells from healthy donors were stimulated with autologous MM preinfected with BCG (intracellular BCG). In the second, the NW cells were directly incubated with BCG, which was therefore extracellular. In the presence of MM, CD4+ T lymphocytes were the cell subset mainly expressing the activation marker, CD25, and proliferating with a peak after 7 days of culture. In contrast, in response to extracellular BCG, the peak of the proliferative response was observed after 6 days of stimulation, and CD56+ CD3– cells (NK cells) were the cell subset preferentially involved. Such proliferation of NK cells did not require a prior sensitization to mycobacterial antigens, and appeared to be dependent upon contact between cell populations and bacteria. Following stimulation with extracellular BCG, the majority of interferon‐γ (IFN‐γ)‐producing cells were NK cells, with a peak IFN‐γ production at 24–30 hr. Interleukin (IL)‐2 and IL‐4 were not detectable in NK cells or in CD3+ T lymphocytes at any time tested. IL‐12 was not detectable in the culture supernatant of NW cells stimulated with extracellular BCG. Compared to the non‐stimulated NW cells, the NW cells incubated for 16–20 hr with BCG induced the highest levels of expression of apoptotic/death marker on the NK‐sensitive K562 cell line. BCG also induced expression of the activation marker, CD25, and proliferation, IFN‐γ production and cytotoxic activity, on negatively selected CD56+ CD3− cells. Altogether, the results of this study demonstrate that extracellular mycobacteria activate several NK‐cell functions and suggest a possible alternative mechanism of NK‐cell activation as the first line of defence against mycobacterial infections.
Thyroglobulin as an autoantigen: what can we learn about immunopathogenicity from the correlation of antigenic properties with protein structure?
Authors: Gentile Fabrizio , Conte Marisa , Formisano Silvestro 
Published: April 2004

SummaryAutoantibodies against human thyroglobulin are a hallmark of autoimmune thyroid disease in humans, and are often found in normal subjects. Their pathogenic significance is debated. Several B‐cell epitope‐bearing peptides have been identified in thyroglobulin. They are generally located away from the cysteine‐rich regions of tandem sequence repetition. It is possible that our current epitopic map is incomplete because of the difficulty that proteolytic and recombinant approaches have in restituting conformational epitopes based upon proper pairing between numerous cysteinyl residues. Furthermore, the homology of cysteine‐rich repeats with a motif occurring in several proteins, endowed with antiprotease activity, suggests that these regions may normally escape processing and presentation to the immune system, and brings attention to the mechanisms, such as oxidative cleavage, by which such cryptic epitopes may be exposed. A number of T‐cell epitope‐bearing peptides, endowed with thyroiditogenic power in susceptible mice, were also identified. None of them was dominant, as none was able to prime in vivo lymph node cells that would proliferate or transfer autoimmune thyroiditis to syngeneic hosts, upon stimulation with intact thyroglobulin in vitro. More than half of them are located within the acetylcholinesterase‐homologous domain of thyroglobulin, and overlap B‐cell epitopes associated with autoimmune thyroid disease, while the others are located within cysteine‐rich repeats. The immunopathogenic, non‐dominant character of these epitopes also favours the view that the development of autoimmune thyroid disease may involve the unmasking of cryptic epitopes, whose exposure may cause the breaking of peripheral tolerance to thyroglobulin. Further research in this direction seems warranted.
Normal human pregnancy is associated with an elevation in the immune suppressive CD25+ CD4+ regulatory T‐cell subset
Authors: Somerset David A. , Zheng Yong , Kilby Mark D. , Sansom David M. , Drayson Mark T. 
Published: April 2004

SummaryCD4+ CD25+ T regulatory cells (TReg), suppress antigen‐specific immune responses and are important for allograft tolerance. During pregnancy the mother tolerates an allograft expressing paternal antigens (the fetus) requiring substantial changes in immune regulation over a programmed period of time. We analysed whether immune‐suppressive TReg cells were altered during pregnancy and therefore might play a part in this tolerant state. The presence of TReg cells was assessed in the blood of 25 non‐pregnant, 63 pregnant and seven postnatal healthy women by flow cytometry. We observed an increase in circulating TReg cells during early pregnancy, peaking during the second trimester and then a decline postpartum. Isolated CD25+ CD4+ cells expressed FoxP3 messenger RNA, a marker of TReg cells, and suppressed proliferative responses of autologous CD4+ CD25– T cells to allogeneic dendritic cells. These data support the concept that normal pregnancy is associated with an elevation in the number of TReg cells which may be important in maintaining materno‐fetal tolerance.
The use of dextromethorphan to treat repetitive self‐directed scratching, biting, or chewing in dogs with allergic dermatitis
Authors: Dodman N. H. , Shuster L. , Nesbitt G. , Weissman A. , Lo W.‐Y. , Chang W.‐W. , Cottam N. 
Published: April 2004

Objective:  To evaluate the efficacy of oral dextromethorphan in dogs with a repetitive behavior problem (self‐licking, self‐chewing, and self‐biting associated with chronic allergic dermatitis).Animals:  Fourteen dogs with chronic allergic dermatitis were enrolled in the study. Twelve dogs completed the study.Procedure:  The dogs were treated for 2 weeks each with dextromethorphan (2 mg/kg BID) and placebo in a randomized, double blind, crossover designed study. A dermatology score, including an assessment of affected areas of the integument and the level of self‐directed behavior, was generated before and following each 2‐week phase of the study. Owners were required to record daily the amount of time they spent with their dog and the amount of time that the dog was observed to be engaged in any of the specified self‐directed behaviors.Results:  The percent of the observed time that the dogs were reported to be involved in self‐directed behaviors was significantly less during the 2‐week active drug treatment phase. The pruritus score component of the dermatology score also was significantly less during the active treatment phase. In addition, a dermatologist‐rated global assessment was more favorable in 11 of 12 dogs following the active treatment phase.Conclusions:  Dextromethorphan significantly reduces the percentage of time that allergic dogs spend self‐licking, self‐chewing, and self‐biting.Clinical relevance:  Dextromethorphan may be a useful adjunct in the management of self‐directed behaviors associated with allergic dermatitis and possibly in other repetitive behaviors as well.
Glucoprivation increases expression of neuropeptide Y mRNA in hindbrain neurons that innervate the hypothalamus
Authors: Li Ai‐Jun , Ritter Sue 
Published: April 2004

AbstractThe hypothalamus is jointly innervated by hindbrain and hypothalamic neuropeptide Y (NPY) cell bodies. While the specific roles of these distinct sources of innervation are not known, NPY neurotransmission within the hypothalamus appears to contribute to glucoregulatory feeding. Here we examine the involvement of hindbrain NPY neurons in glucoregulation using in situ hybridization to assess their responsiveness to glucoprivation. The hindbrain NPY innervation of the hypothalamus is derived from cell bodies that coexpress norepinephrine or epinephrine. Therefore, we quantified NPY mRNA hybridization signal in hindbrain catecholamine cell groups 90 min after subcutaneous administration of the glycolytic inhibitor 2‐deoxy‐d‐glucose (2DG, 250 mg/kg) to male rats. Catecholamine cell groups A1, A1/C1 and C2 (that provide the major NPY innervation of the hypothalamus) showed a basal level of NPY mRNA hybridization signal that was dramatically increased by 2DG. In C1 and C3, where basal NPY mRNA expression was close to or below our detection threshold, the hybridization signal was also significantly increased by 2DG. In cell groups A2, A5, A6 and A7, neither basal nor 2DG‐stimulated NPY mRNA expression was detected. Hypothalamic microinjection of the retrogradely transported catecholamine immunotoxin saporin conjugated to anti‐dopamine‐β‐hydroxylase destroyed hindbrain catecholamine/NPY neurons and abolished basal and 2DG‐stimulated increases in NPY expression in hindbrain cell groups. The responsiveness of hindbrain NPY neurons to glucose deficit suggests that these neurons participate in glucoprivic feeding or other glucoregulatory responses.
Thrombin reduces MuSK and acetylcholine receptor expression along with neuromuscular contact size in vitro
Authors: Faraut Brice , Ravel‐Chapuis Aymeric , Bonavaud Sylvie , Jandrot‐Perrus Martine , Verdière‐Sahuqué Martine , Schaeffer Laurent , Koenig Jeanine , Hantaï Daniel 
Published: April 2004

AbstractIn the course of studies on thrombin and its inhibitor(s) in synaptic plasticity, we addressed the question of their roles in the formation of neuromuscular junctions (NMJ) and used a model of rat neuron–myotube cocultures. We report that the size of acetylcholinesterase (AChE) patches used as a marker of neuromuscular contacts was decreased in the presence of either thrombin or SFLLRN, the agonist peptide of the thrombin receptor PAR‐1, whereas it was increased with hirudin, a specific thrombin inhibitor. In an attempt to relate these neuromuscular contact size variations to molecular changes, we studied muscle‐specific tyrosine kinase receptor (MuSK), acetylcholine receptor (AChR) and rapsyn expression in the presence of thrombin. We showed that thrombin did not change rapsyn gene and protein expression. However, the expression of MuSK and surface AChR proteins was diminished in both myotube cultures and neuron–myotube cocultures. These reductions in protein expression were associated with a decrease in MuSK and AChR α‐subunit gene expression in myotube cultures but not in neuron–myotube cocultures. Moreover, the expression of the AChR ε‐subunit gene, specifically enhanced by neuron‐released factors, was not modified by thrombin in neuron–myotube cocultures. This suggests that thrombin did not affect the expression of synaptic AChRs enhanced by neuron‐released factors but rather reduced the level of extrasynaptic AChRs. Taken together, these results indicate that thrombin in balance with its inhibitor(s) could modulate the formation of neuromuscular contacts in vitro by affecting the expression of two essential molecules in NMJ postsynaptic differentiation, MuSK and AChR.