bluuebunny/crossref_metadata_2025 huggingface dataset:
Antigen‐Pulsed, Interleukin‐4‐Treated B Cells Activate Primed T Cells In Vitro but not Naive T Cells In Vivo
Authors: GRAINGER R. , HART D. N. J. , WATSON J. D. , BAIRD M. A.
Published: July 2006

The ability of B cells to act as effective antigen‐presenting cells is a source of debate which centres on the degree of activation of either B cells or T cells. We have investigated whether B cells treated with interleukin 4 (IL‐4) can express the two signals required to activate T cells: MHC Class 2/antigenic peptide complexes(signal 1) and the costimulatory molecules B7‐1 and B7‐2 (signal 2). We have also determined whether these cells could activate atitigen‐experienced T cells in vitro and whether they could prime naive T cells in vivo. We found that B cells expressed abutidant MHC Class 2 molecules and moderate levels of B7‐2 after 24 h culture in IL‐4 with or without purified protein derivative (PPD) but B7‐1 was not detectable. PPD‐pulsed, IL‐4 treated B cells induced antigeti‐experienced T cells to proliferate in vitro but these cells failed to prime naive T cells in vivo when injected itito mice. We conclude that signals, in addition to those mduced with IL‐4, are required for B cells to initiate an immutie respotise to atitigen.
Immunobiological Studies on Experimental Visceral Leishmaniasis IV. Kinetics of Evolution of Disease‐Promoting Versus Host‐Protective Cells of Monocyte‐Macrophage Lineage and their Characterization
Authors: SAHA B. , BANDYOPADHYAY D. , ROY S. , Roy Dr Syamal
Published: July 2006

The evolution of cells of the monocyte‐macropbage lineage (MML cells) in the spleen of Leishmania donovani (LD) infected BALB/c mice was studied. Spleen cells were fractionated on a discontinuous percoll gradient and adherent cells (AC) were purified from fractionated spleen cells by adherence steps that appeared at the interfaces of 25–35%, 35–40%, 40–45% and 45–50% percoll gradients. The AC were characterized as MML cells on the basis of positive staining for non‐specific esterase. Adherent cells that appeared at the interfaces of 25–35% and 40–45% were defined as A and C, respectively, and both of them showed extreme variation in a progressive infection. It was observed that A supported parasite replication whereas C remained refractory when infected with LD in vitro. Furthermore, when A cells and C cells were used as antigen‐presenting cells to stimulate mixed population of IFN‐γ producing and IL‐4 producing T‐cells, it was observed that IL‐4 and IFN‐γ were the predominating cytokine in the T‐cell supernatant, respectively. Both A and C were found to be increased hand‐in‐hand up to 5 months of infection and from then on A decreased and C increased in their numerical strength (A‐C reciprocity). The evolution of A‐C reciprocity coincided with the gradual reduction in the parasitaemia in the spleen suggesting that this may contribute to the acquisition of anti‐leishmania immunity.
Calprotectin‐Mediated Zinc Chelation as a Biostatic Mechanism in Host Defence
Authors: CLOHESSY P. A. , GOLDEN B. E.
Published: July 2006

The S‐100 Ca2+ binding protein, calprotectin, isolated from neutrophil lysates, has been reported to exhibit zinc reversible biostatic activity in vitro. We verified these findings with C. albicans and investigated whether the growth inhibition resulted from zinc deprivation due to chelation by calprotectin. Calprotectin concentrations of 250 μg/ml significantly inhibited the growth of C. albicans. This was reversed by supplementing culture medium with 10 μM ZnSO4. Incubation of calprotectin in culture medium for 24 h prior to inoculation significantly reduced the minimum inhibitory concentration. When this latter medium was ultrafiltered to remove the calprotectin and then inoculated with C. albicans, significant growth inhibition was still present: again it was reversed by zinc. These findings implicate zinc chelation as a novel, potentially important host defence function of an abundant neutrophil protein.
Distributions of HLA Class II Alleles in Autoantibody Subsets Among Norwegian Patients with Systemic Lupus Erythematosus
Authors: SKARSVÅG S. , HANSEN K. E. , MOEN T. , EGGEN B. M.
Published: July 2006

In order to find potential correlations between HLA class II alleles and anti‐SS‐A, ‐SS‐B, ‐Sm and anti‐snRNP responses among Norwegian patients with systemic lupus erythematosus (SLE), HLA‐DRB1, ‐DRB3*0101, ‐DQA1 and ‐DQB1 alleles were determined by DNA typing 50 patients and 108 controls. HLA distributions were analysed in the following autoantibody subgroups: anti‐SS‐A with ‐SS‐B, anti‐SS‐A without ‐SS‐B, anti‐snRNP without ‐Sm, anti‐SS‐A without ‐snRNP and anti‐snRNP without ‐SS‐A. The autoantibodies were detected by EIA (enzyme immunuassay). Patients with anti‐SS‐A and ‐SS‐B had significantly increased frequencies of DRB1*03, DRB3*0101, DQA1*0501, DQB 1*0201 (in linkage disequilibrium) versus controls and versus patients without anti‐SS‐A and ‐SS‐B. No differences in HLA distribution were found when the group with anti‐SS‐A alone was compared to the group with anti‐SS‐A and concomitant ‐SS‐B. Comparing the groups with and without anti‐SS‐A and ‐SS‐B, the highest RR were found for the alleles DRB1*03, DRB3*0101, DQB1*0501, DQB1*0201 (in linkage disequilibrium) with RR: 16.8, 5.0, 19.6, 10.3, respectively, P<0.05). RR for DQw2/DQw6 heterozygotes was 3.5 (Ns.), and RR for cases having DQa molecules with glutamine in position 34 and DQ/3 molecules with leucine in position 26 on both chains was 6.3 (P <0.05). No HLA associations were observed in the group with anti‐snRNP without concomitant ‐Sm or without concomitant ‐SS‐A. These results show that production of anti‐SS‐A and ‐SS‐B is associated to the HLA alleles DRB1*03, DRB3*0101, DQA1*0501, DQB1*0201, and that this haplotype shows stronger correlation to these responses than DQw2/DQw6 heterozygosity or HLA molecules having glutamine in position 34 (DQa) and leucine in position 26 (DQ/3). The failure to observe any correlation with DRB1*15, 16 (DR2) in the group with anti‐SS‐A alone may demonstrate ethnic differences concerning this response. The failure to identify any HLA associations for the anti‐snRNP response may reflect the heterogeneity of the molecules that constitute this antigen.
Correlation of IgG Fc Receptors on Granulocytes with Serum Immune Complex Level in Systemic Lupus Erythematosus
Authors: SZÜCS G. , KÁVAI M. , KISS E. , CSIPÖ I. , SZEGEDI GY.
Published: July 2006

The expression of FcγRI, FcγRII and FcγRIII on granulocytes in the blood of patients with systemic lupus erythematosus was investigated. The relationship between the receptor expression and serum immune complex (IC) concentration was analysed. The decrease in mean fluorescence intensity of both FCγRII and FcγRIII of patients' granulocytes stained by specific monoclonal antibodies (using MoAb IV. 3 and 3G8) was significant. The detected decrease of FcγRII was inversely correlated with the high circulating IC level in patients' sera.
High Expression of Membrane Cofactor Protein of Complement (CD46) in Human Leukaemia Cell Lines: Implication of an Alternatively Spliced Form Containing the STA Domain in CD46 Up‐Regulation
Authors: HARA T. , SUZUKIt Y. , SEMBAJ T. , HATANAKA M. , MATSUMOTO M. , SEYA T.
Published: July 2006

Human membrane cofactor protein (MCP, CD46) is a receptor for the measles virus and serves as a complement regulator which protects host cells from autologous complement attack. MCP is highly polymorphic due to a variety of mRNA splice products. The levels of MCP expression on T and myeloid cell lines are usually two‐eightfold higher than those on their normal counterparts, whereas Burkitt's lymphoma B cell lines express less MCP than B cell lineages carrying no EB virus. The molecule has a Ser/Thr‐rich (ST) domain adjacent to the functional domain, namely short consensus repeats (SCR). The ST domain and a cytoplasmic tail (CYT) contribute to the MCP polymorphism. The ST domain is encoded by three exons (A, B and C) and major ST iscforms are STABC, STBC and STC. The authors investigated the relationship between the expression levels and isoform usage of MCP by flow cytometry using specific antibodies against STA and STC, by reverse transcriptase‐polymerase chain reaction (RT‐PCR) with size markers for each splice variant, and by RT‐PCR/Southern blotting using a specific probe for STA. The results were (1) the profiles of mean shifts of myeloid and T cell lines were STC < STA on flow cytometry while those of B cell lines and normal blood cells were STa < STC; (2) all cell lines tested by RT‐PCR expressed the messages for the isoforms STBC/CYTl, STC/CYTl, STBC/CYT2, and STC/CYT2. The band for STABC/CYT2 overlapped that for STC/CYTl, and the band for STABC/CYTl was marginal in all cell lines examined; (3) semi‐quantitative analysis of the STABC isoforms by Southern blotting indicated the presence of high levels of the STABC messages in myeloid and T‐cell lines in comparison with B lymphoid cells and normal leucocytes. Thus, the quantity of MCP expressed parallels the STABC message level, which is up‐regulated in T and myeloid leukaemia cell lines.
Engraftment and Humoral Immunity in SCID and RAG‐2‐Deficient Mice Transplanted with Human Peripheral Blood Lymphocytes
Authors: STEINSVIK T. E. , GAARDER P. I. , AABERGEf I. S. , LØVIK M.
Published: July 2006

SCID and RAG‐2 deficient mice were transplanted intraperitoneally with human peripheral blood lymphocytes (hu‐PBL‐SCID and hu‐PBL‐RAG mice). Seven days after transplantation tbe mice were immunized with a pneumococcal polysaccharide vaccine. Flow cytometry analysis of cells from the peritoneal cavity and the spleen after 8–10 weeks revealed that human cells had more limited engraftment in RAG than in SCID recipient mice, and that more human cells were found in the spleen than in the peritoneal cavity. Functionality of the human cells recovered from these two locations was explored by the counting of human immunoglobulin secreting cells (hu‐ISC). A total of 83% of the hu‐PBL‐SCID mice and 29% of the hu‐PBL‐RAG mice had detectable hu‐ISC in the peritoneal cavity and/or the spleen. The kinetic profiles of human immunoglobulins in the mouse sera during the experiment showed donor dependency. More than 90% of the hu‐PBL‐SCID mice had detectable levels of human IgG, IgM and IgA, while 78% had detectable levels of IgE, whereas detectable levels of IgG, IgM, IgA and IgE were measured in 37%, 64%, 68% and 23% of the hu‐PBL‐RAG mice, respectively. Forty‐seven per cent of immunized hu‐PBL‐SCID mice showed a human antipneumococcal IgG level that was significantly above the background level in non‐immunized mice, while none of the hu‐PBL‐RAG mice produced any detectable levels of human antipneumococcal IgG. In short, human PBL showed a better engraftment and a better antibody response when transplanted into SCID mice than into RAG mice.
Sehistosoma Mansoni in the Baboon: Modulation of Pathology After Vaccination with Polyclonal Anti‐Idiotypic Antibodies
Authors: NYINDO M. , BORUS P. K. , FARAH I. O. , OGUYA F. O. , MAKAWITI D. W.
Published: July 2006

Vaccination of five baboons with an anti‐idiotypic vaccine to irradiated Schistosoma mansoni cercariae resulted in nearly 19% protection compared to 39% protection conferred to five baboons vaccinated with an irradiated vaccine. Vaccination with the anti‐idiotypic antibodies resulted in a significant reduction of pathology and granuloma size following challenge with live unattenuated cercariae. Results presented in this work are considered highly significant because the anti‐idiotypic vaccine markedly influenced schistosomiasis morbidity which is the main consideration in this disease.
Human Intestinal B‐Cell Blasts and Plasma Cells Express the Mucosal Homing Receptor Integrin α4β7
Authors: FARSTAD I. N. , HALSTENSEN T. S. , LAZAROVITS A. I. , NORSTEIN J. , FAUSA O. , BRANDTZAEG P.
Published: July 2006

Interactions between homing receptors on circulating leucocytes and endothelial addressins regulate tissue‐specific cellular extravasation. Although integrin á4β7 appears to be the main receptor for guthoming T lymphocytes, less is known about molecules mediating mucosal B cell homing. Expression of integrin α4β7 on B lymphocytes, B cell blasts, and plasma cells in human gut‐associated lymphoid tissue (GALT; the Peyer's patches and appendix) and lamina propria was studied by multi‐colour immunofluorescence applied on cryosections. Isolated mononuclear cells from the same tissue compartments were examined by flow cytometry and compared with peripheral blood B cells. Integrin α4β7 was expressed by IgA+ B cell blasts and plasma cells (CD38high) in the lamina propria, B cell blasts in GALT, and sIgD+ B lymphocytes in peripheral blood. In contrast, GALT sIgD+ B lymphocytes were negative or only weakly positive for α4β7. These results suggested that B lymphocytes down‐regulate αAβ7 upon extravasation in GALT but up‐regulate this integrin after antigen‐priming. Thus, α4β7 may be a homing receptor also for B cell blasts extravasating in the gut lamina propria, where this integrin is maintained on plasma cells, perhaps as a local retention factor.
Tenidap, but not Nonsteroidal Anti‐Inflammatory Drugs, Inhibits T‐Cell Proliferation and Cytokine Induction
Authors: DOLHAIN R. J. E. M. , DE KUIPER P. , VERWEIJ C. L. , FENDERS J. M. A. , BREEDVELD F. C. , DIJKMANS B. A. C. , MILTENBURG A. M. M.
Published: July 2006

T‐lymphocytes are involved in the inflammatory response that occurs in affected joints of patients with rheumatoid arthritis (RA). Some second‐line disease modifying anti‐rheumatic drugs used in the treatment of patients with RA are known to block T‐cell activation. The present study assessed whether tenidap, an investigational anti‐rheumatic drug, affects in vitro T‐cell responses such as proliferation and cytokine production. It was found that tenidap, in contrast to several nonsteroidal anti‐inflammatory drugs, inhibits anti‐CD3 or IL‐2 driven proliferative responses of cloned human T‐cells. Furthermore, tenidap was found to inhibit IFN‐γproduction as well as the induction of mRNA encoding IFN‐γ or TNF‐α. The results indicate that tenidap may exert at least part of its anti‐inflammatory activity via inhibition of T‐cell function and cytokine production.
Lyme Neuroborreliosis: Evidence for Persistent Up‐Regulation of Borrelia Burgdorferi‐Reactive Cells Secreting Interferon‐γ
Authors: WANG W.‐Z. , FREDRIKSON S. , SUN J.‐B. , LINK H.
Published: July 2006

The T‐cell response to the aetiologic pathogen Borrelia (B.) burgdorferi in patients with Lyme neuroborreliosis (LN) and in control patients with other neurological diseases was examined by enumerating B. burgdorferi‐reactive T cells secreting interferon‐γ (IFN‐γ) with an ELIspot assay. LN patients had elevated numbers of B. burgdorferi‐reactive IFN‐γ secreting cells in blood and approximately 20‐fold enriched in the cerebrospinal fluid (CSF). A positive correlation existed in CSF between B. burgdorferi‐reactive IFN‐γ secreting cells and B cells secreting anti‐B. burgdorferi IgG antibodies. The up‐regulation of antigen‐specific IFN‐γ secreting cells persisted in peripheral blood up to at least 9 months and in the CSF for at least 4 months after termination of treatment with antibiotics, when the patients were mostly free from clinical signs and symptoms due to LN. How IFN‐γ interplays with other cytokines and influences the pathogenesis of LN remains to be studied.
Arabidopsis cpFtsY mutants exhibit pleiotropic defects including an inability to increase iron deficiency‐inducible root Fe(III) chelate reductase activity
Authors: Durrett Timothy P. , Connolly Erin L. , Rogers Elizabeth E.
Published: July 2006

All plants, except for the grasses, must reduce Fe(III) to Fe(II) in order to acquire iron. In Arabidopsis, the enzyme responsible for this reductase activity in the roots is encoded by FRO2. Two Arabidopsis mutants, frd4‐1 and frd4‐2, were isolated in a screen for plants that do not induce Fe(III) chelate reductase activity in their roots in response to iron deficiency. frd4 mutant plants are chlorotic and grow more slowly than wild‐type Col‐0 plants. Additionally, frd4 chloroplasts are smaller in size and possess dramatically fewer thylakoid membranes and grana stacks when compared with wild‐type chloroplasts. frd4 mutant plants express both FRO2 and IRT1 mRNA normally in their roots under iron deficiency, arguing against any defects in systemic iron‐deficiency signaling. Further, transgenic frd4 plants accumulate FRO2‐dHA fusion protein under iron‐deficient conditions, suggesting that the frd4 mutation acts post‐translationally in reducing Fe(III) chelate reductase activity. FRO2‐dHA appears to localize to the plasma membrane of root epidermal cells in both Col‐0 and frd4‐1 transgenic plants when grown under iron‐deficient conditions. Map‐based cloning revealed that the frd4 mutations reside in cpFtsY, which encodes a component of one of the pathways responsible for the insertion of proteins into the thylakoid membranes of the chloroplast. The presence of cpFtsY mRNA and protein in the roots of wild‐type plants suggests additional roles for this protein, in addition to its known function in targeting proteins to the thylakoid membrane in chloroplasts.
Arabidopsis MAP kinase 4 regulates salicylic acid‐ and jasmonic acid/ethylene‐dependent responses via EDS1 and PAD4
Authors: Brodersen Peter , Petersen Morten , Bjørn Nielsen Henrik , Zhu Shijiang , Newman Mari‐Anne , Shokat Kevan M. , Rietz Steffen , Parker Jane , Mundy John
Published: July 2006

Arabidopsis MPK4 has been implicated in plant defense regulation because mpk4 knockout plants exhibit constitutive activation of salicylic acid (SA)‐dependent defenses, but fail to induce jasmonic acid (JA) defense marker genes in response to JA. We show here that mpk4 mutants are also defective in defense gene induction in response to ethylene (ET), and that they are more susceptible than wild‐type (WT) to Alternaria brassicicola that induces the ET/JA defense pathway(s). Both SA‐repressing and ET/JA‐(co)activating functions depend on MPK4 kinase activity and involve the defense regulators EDS1 and PAD4, as mutations in these genes suppress de‐repression of the SA pathway and suppress the block of the ET/JA pathway in mpk4. EDS1/PAD4 thus affect SA–ET/JA signal antagonism as activators of SA but as repressors of ET/JA defenses, and MPK4 negatively regulates both of these functions. We also show that the MPK4–EDS1/PAD4 branch of ET defense signaling is independent of the ERF1 transcription factor, and use comparative microarray analysis of ctr1, ctr1/mpk4, mpk4 and WT to show that MPK4 is required for induction of a small subset of ET‐regulated genes. The regulation of some, but not all, of these genes involves EDS1 and PAD4.
The Arabidopsis pex12 and pex13 mutants are defective in both PTS1‐ and PTS2‐dependent protein transport to peroxisomes
Authors: Mano Shoji , Nakamori Chihiro , Nito Kazumasa , Kondo Maki , Nishimura Mikio
Published: July 2006

Peroxisome biogenesis requires various complex processes including organelle division, enlargement and protein transport. We have been studying a number of Arabidopsis apm mutants that display aberrant peroxisome morphology. Two of these mutants, apm2 and apm4, showed green fluorescent protein fluorescence in the cytosol as well as in peroxisomes, indicating a decrease of efficiency of peroxisome targeting signal 1 (PTS1)‐dependent protein transport to peroxisomes. Interestingly, both mutants were defective in PTS2‐dependent protein transport. Plant growth was more inhibited in apm4 than apm2 mutants, apparently because protein transport was more severely decreased in apm4 than in apm2 mutants. APM2 and APM4 were found to encode proteins homologous to the peroxins PEX13 and PEX12, respectively, which are thought to be involved in transporting matrix proteins into peroxisomes in yeasts and mammals. We show that APM2/PEX13 and APM4/PEX12 are localized on peroxisomal membranes, and that APM2/PEX13 interacts with PEX7, a cytosolic PTS2 receptor. Additionally, a PTS1 receptor, PEX5, was found to stall on peroxisomal membranes in both mutants, suggesting that PEX12 and PEX13 are components that are involved in protein transport on peroxisomal membranes in higher plants. Proteins homologous to PEX12 and PEX13 have previously been found in Arabidopsis but it is not known whether they are involved in protein transport to peroxisomes. Our findings reveal that APM2/PEX13 and APM4/PEX12 are responsible for matrix protein import to peroxisomes in planta.
The central coiled‐coil domain and carboxyl‐terminal WD‐repeat domain of Arabidopsis SPA1 are responsible for mediating repression of light signaling
Authors: Yang Jianping , Wang Haiyang
Published: July 2006

Arabidopsis constitutive photomorphogenic 1 (COP1) is an E3 ubiquitin ligase that directly binds and targets for degradation a number of photomorphogenesis‐promoting transcription factors, including HY5 and HFR1, to desensitize light signaling. Arabidopsis suppressor of phyA‐105 (SPA1), which encodes a protein structurally related to COP1, also acts to repress photomorphogenesis under various light conditions. Here we show that overexpression of Arabidopsis SPA1 results in a hyperetiolation phenotype and reduced accumulation of HY5 and HFR1. In addition, we show that both COP1 and SPA1 are each dependent on the presence of the other for their repressive effect on light signaling. Moreover, we demonstrate that both the central coiled‐coil and the C‐terminal WD‐repeat domains of SPA1 are necessary, and together these two domains are sufficient for repressing photomorphogenesis. However, the N‐terminal kinase‐like domain of SPA1 contributes to its full activity and promotes destabilization of the SPA1 protein. Together, our results substantiate the notion that COP1 and SPA1 act in concert to form a functional E3 ubiquitin ligase complex and provide a molecular basis for understanding the structure–function relationship of SPA1.
Tricuspid valve replacement after cardiac transplantation
Authors: Raghavan Ramya , Cecere Renzo , Cantarovich Marcelo , Giannetti Nadia
Published: July 2006

Abstract:  Background:  Tricuspid regurgitation (TR) occurs commonly in transplanted hearts. Although theoretically attractive, tricuspid valve replacement (TVR) has not been widely investigated as a possible therapy in post‐transplant patients. The purpose of this study was to determine the safety of TVR in heart transplant patients and its effects on measurable clinical endpoints.

Methods:  We acquired data by both retrospective chart review and prospective data collection in all patients who underwent TVR after cardiac transplantation.

Results:  Nine patients were identified and followed for a period of six months. The age of patients at time of TVR was 62 ± 6.1 yr and their average time since transplantation was 12 ± 3.2 yr. Most patients demonstrated a reduction in their furosemide dose (105 ± 63 mg/d pre‐TVR vs. 67.5 ± 65 mg/d post‐TVR, p = 0.001) with a reduction in serum creatinine levels (188 ± 72 μmol/L pre‐TVR vs. 143 ± 42 μmol/L post‐TVR, p = 0.06). Additionally, we found a significant improvement in albumin values (32 ± 5 g/L pre‐TVR vs. 42 ± 3 g/L post‐TVR, p = 0.002) as well as an improvement in total bilirubin (35 ± 18 μmol/L pre‐TVR vs. 18 ± 5 μmol/L post‐TVR, p = 0.05). There was only one death in our series, in the only patient with known severe graft atherosclerosis.

Conclusions:  TVR appears to be a safe procedure in patients without severe graft atherosclerosis with improvements in serum creatinine, albumin and total bilirubin values, in addition to a reduction in furosemide dose. This may reflect improved forward flow, improved symptomatology from TR as well as possible beneficial effects on nutritional status.
Quantification of a low cellular immune response to aid in identification of pediatric liver transplant recipients at high‐risk for EBV infection
Authors: Lee Timothy C. , Goss John A. , Rooney Cliona M. , Heslop Helen E. , Barshes Neal R. , Caldwell Yvette M. , Gee Adrian P. , Scott Jaymee D. , Savoldo Barbara
Published: July 2006

Abstract:  Objective:  Uncontrolled EBV infection leading to lymphoproliferative disease is a significant cause of morbidity in pediatric orthotopic liver transplant (OLT) recipients. Herein, we describe the use of a novel immune assay, which quantifies the lymphocyte immune response and correlates the value to risk for EBV infection.

Methods:  All patient data were prospectively collected between 2003 and 2005. The study included 18 pediatric liver transplant recipients, seven males and 11 females with a mean follow‐up of 47 months post‐OLT. Patient EBV load was monitored using real‐time quantitative PCR (qPCR). The ATP release (ng/mL) of CD3+ lymphocytes after mitogenic stimulation with phytohemagluttinin (PHA; Cylex Corporation) was used to quantitate patient immune response. Patients were stratified by EBV load: low (<1000 copies/μg DNA), medium (1000–4000 copies/μg DNA), and high (>4000 copies/μg DNA).

Results:  Patients with low EBV loads had a significantly (p < 0.04) stronger immune response to PHA than patients with EBV load >1000 copies/μg DNA. Further analysis demonstrated that patients with ATP level <125 ng/mL had 100% probability of an EBV titer >4000 copies/μg DNA, when compared with 22% if the ATP level was between 125 and 400 ng/mL or only 15% if >400 ng/mL (p < 0.05). When immunosuppression was reduced, we observed an increase of the ATP release that correlated with a decrease of the EBV viral load.

Conclusion:  In conclusion, this study investigates the use of a lymphocyte activation assay to closely measure the immunosuppression status of pediatric liver transplant recipients. Because measurement of EBV DNA load as a single parameter has a poor positive predictive value for development of PTLD, the association of these assays may be of help in the identification of patients at risk for PTLD.
PCR assays for the early detection of BKV infection in 125 Spanish kidney transplant patients
Authors: Vera‐Sempere Francisco J. , Rubio Luis , Felipe‐Ponce Vanesa , García Ana , Mayordomo Fernando , Sánchez‐Plumed Jaime , Beneyto Isabel , Ramos David , Zamora Isabel , Simón José
Published: July 2006

Abstract:  BK virus (BKV) reactivation arises from immunocompromised conditions and can produce a tubulointerstitial nephropathy (BKVN) in kidney transplant recipients (KTR). Approximately 5% of KTR develop BKVN, and about 45% of these lose their graft. Therefore, using molecular tools to test for BKV may be helpful in early detection. A series of 125 Spanish KTR, originating from a single transplant center, were studied in relation to BKV infection in the first post‐transplant year. First, we carried out a urinary cytological study, looking for decoy cells as a possible marker of virus replication. Secondly, in all positive cytological samples and in some negative cytological samples (selected at random), we performed qualitative polymerase chain reaction (PCR) assays in serum and urine amplifying two different genome regions (LT and VP1). A transcription control region (TCR)‐BK polymorphism sequence analysis was also performed in those BK PCR positive cases. Twenty‐three of 125 (18.4%) KTR presented decoy cells in at least one urinary cytological sample. Molecular studies revealed that 10 of 125 (8%) KTR were BK PCR‐serum positive cases (seven LT+/VP1− and three LT+/VP1+); and 13 of 40 (32.5%) KTR were BK PCR‐urine positive cases (five LT+/VP1− and eight LT+/VP1+). When we compared PCR‐urine and cytological results in 40 KTR, only 15% (six cases) revealed simultaneous positivity in both studies. In the context of clinical graft dysfunction, three patients demonstrated BK DNA presence in the renal biopsy. Finally, sequence analysis of the TCR was performed in 13 BK‐PCR positive cases determining the AS, JL, WW, and WW‐like viral variants. TCR sequence analysis, allows us to demonstrate the possible implication of the donor in BK infection studying four BK‐PCR positive patients paired by donor.
SDF‐1 expression is elevated in chronic human renal allograft rejection
Authors: Hoffmann U. , Banas B. , Krüger B. , Banas M. , Bergler T. , Böger C. , Kammerl M. , Obed A. , Rümmele P. , Segerer S. , Riegger G. A. J. , Krämer B. K.
Published: July 2006

Abstract:  The exact mechanism of acute and chronic allograft rejection still remains unclear. The chemokine SDF‐1 as mediator of allograft rejection has been under intensive investigation in liver, cardiac and bone marrow transplantation, whereas in renal transplantation, there are no reports about SDF‐1 to date. This study was performed to evaluate if SDF‐1 might also play an important role in human renal graft biopsies. One hundred and ninety formalin‐fixed, paraffin‐embedded renal allograft biopsies were included in the analysis from patients with normal renal graft morphology (according to Banff 97 classification grade 1, n = 84), with acute interstitial rejection (Banff grade 4 type I, n = 10), with acute vascular rejection (Banff grade 4 type II, n = 21), with chronic allograft nephropathy (CAN, Banff grade 5, n = 23), and without rejection but with various other lesions (Banff grade 6, n = 42). SDF‐1 was localized by immunohistochemistry. In biopsies with CAN, SDF‐1 expression was significantly elevated in interstitial infiltrates and infiltrating neointimal cells of arteries compared with biopsies with normal renal graft morphology. This is the first study describing a role of SDF‐1 in human renal allograft rejection. We were able to demonstrate in a large number of biopsies an upregulation of SDF‐1 in patients with CAN. Whether SDF‐1 has pro‐inflammatory or protective properties in this setting has to be evaluated in further trials.
Attitude of kidney patients on the transplant waiting list toward related‐living donation. A reason for the scarce development of living donation in Spain1
Authors: Martínez‐Alarcón L. , Ríos A. , Conesa C. , Alcaraz J. , González M.J. , Ramírez P. , Parrilla P.
Published: July 2006

Summary:  Introduction:  Most Spanish transplant centers have on‐going living kidney transplant programs. However, such transplants are not increasing as a proportion of the total number of kidney transplants. The objective of this study is to analyze the attitude of kidney patients on the kidney transplant waiting list toward living kidney donation.

Materials and methods:  The patients studied were selected from those included on the kidney transplant waiting list from November 2003 until September 2005 (n = 221). Attitude toward living donation was evaluated using a psychosocial questionnaire. It was completed in a direct personal interview with an independent health‐care worker from the Transplant Unit. Student's t‐test and the chi‐squared test were applied.

Results:  Two hundred and fourteen patients completed the questionnaire (97%), of which 35% would accept a related living kidney if it were offered to them, 60% would prefer to wait on the waiting list and the remaining 5% are undecided. Up to 66% (n = 134) of patients report that a member of their family or a friend have offered them an organ for donation. Eighty‐nine percentage believe that there is some risk involved in living kidney donation, although it is not a factor that affects whether an organ would be accepted or not (p = 0.767). The psychosocial variables that affect attitude toward accepting a related living kidney are: (i) age: the youngest are those who are most likely to accept (40 vs. 45‐yr‐old; p = 0.010); (ii) descendents: patients without descendents are more likely to accept a living organ (56% vs. 27%; p < 0.000); (iii) marital status: a greater percentage of single respondents would be prepared to receive this type of transplant compared to the group of married respondents (55% vs. 30%. p = 0.007); and (iv) level of education: those with a higher level of education are more likely to accept a living organ (43% have secondary or university studies vs. 28% who only have primary education; p = 0.040).

Conclusion:  Patients on the waiting list for a kidney transplant do not have a very favorable attitude toward receiving a related‐living donor organ, although members of their family have offered them one of their organs. The profile of a patient who would accept a related‐living donated kidney is a young, single person, without descendents, and with a high level of education.
Secondary focal segmental glomerulosclerosis following kidney transplantation in a patient with type I diabetes mellitus
Authors: Yamamoto Izumi , Yamamoto Hiroyasu , Mitome Jun , Tanno Yudo , Utsunomiya Yasunori , Miyazaki Yoichi , Yamaguchi Yutaka , Hosoya Tatsuo
Published: June 2006

Abstract:  Although recurrent diabetic nephropathy is common in patients with type I diabetes after kidney transplantation, the development of focal segmental glomerulosclerosis (FGS) is rare, and its development generally takes several years. We report here a case of type I diabetes mellitus with secondary FGS accompanied by proteinuria 10 months following kidney transplantation. Episode biopsy showed secondary FGS, evidenced by glomerular capillary collapse and large epithelial cells with ballooning degeneration. Exudative dense deposition of IgM in a diffuse global mesangial pattern and enlarged glomerular diameters were observed, suggestive of glomerular hyperfiltration which can lead to secondary FGS. An imbalance in body size between donor and recipient and/or uncontrolled diabetes are potential causes of glomerular hyperfiltration. We administered angiotensin‐converting enzyme inhibitor and angiotensin II receptor blocker to reduce hyperfiltration‐induced renal damage; the combination therapy reduced proteinuria from 2346 to 258 mg/d. Secondary FGS should be a consideration after kidney transplantation in patients with type I diabetes mellitus.
Early and late histopathological changes in renal allografts procured by laparoscopic donor nephrectomy
Authors: Shimizu Tomokazu , Tanabe Kazunari , Miyamoto Naoshi , Tokumoto Tadahiko , Ishida Hideki , Toma Hiroshi , Yamaguchi Yutaka
Published: June 2006

Abstract:  Introduction:  Subcapsular cortical damage (SCCD) is a characteristic pathological change, which is seen in renal allograft biopsy specimen obtained immediately after laparoscopic donor nephrectomy (LDN). In this study we evaluated the early and late histopathological effect of SCCD examining renal allograft biopsy specimens obtained after kidney transplantation.

Materials and methods:  Laparoscopic donor nephrectomy was performed on 250 donors between July 2000 and September 2004 in our institution. Allograft biopsy of all 250 kidneys was performed immediately after LDN (zero hour biopsy). Of 250 biopsy specimens, 105 were diagnosed as SCCD and the allograft biopsy specimens obtained from 105 recipients after transplantation were enrolled in this study. All specimens were routinely examined by using light microscopy and immunofluorescence.

Results:  In 87 patients 256 allograft biopsy specimens did not show post‐pathological changes of SCCD. Twenty biopsy specimens obtained from 18 recipients showed tubular necrosis and a partly tubular regeneration and patchy interstitial hemorrhage, which seemed to be caused by SCCD. Ten allograft biopsy specimens from nine recipients demonstrated residual pathologic changes in SCCD early after transplantation. The other 10 specimens from nine recipients had abnormal histopathologic changes including interstitial edema and fibrosis, tubular atrophy and glomerular sclerosis in the subcapsular cortex late after transplantation.

Conclusion:  The early change of SCCD after transplantation remained intact and partial regeneration and the late showed subcapsular fibrosis with glomerular sclerosis. The incidence of the subcapsular lesions due to SCCD after transplantation was 17% in 105 allografts.
Incidence of positive C4d deposition in long‐term survival cases over 10 yr after renal transplantation
Authors: Namba Yukiomi , Oka Kazumasa , Moriyama Toshiki , Kyo Masahiro , Imamura Ryoichi , Shi Yi , Ichimaru Naotsugu , Isaka Yoshitaka , Takahara Shiro , Okuyama Akihiko
Published: June 2006

Abstract:  Background:  The incidence of positive C4d deposition in peritubular capillaries (PTC) in long‐term survival cases remains controversial. Some incidences of positive C4d deposition in PTC in cases of long‐term survival less than 10 yr have been reported. We retrospectively examined the incidence of positive C4d deposition in long‐term survival cases over 10 yr after renal transplantation and the histological and clinical characteristics of the positive C4d staining cases.

Methods:  We examined 14 protocol biopsy cases performed at Osaka University Hospital between March 2004 and March 2005. The average interval between the operation and the day of biopsy was 15.4 yr. Histological diagnosis was made in accordance with the Banff 97 classification. Paraffin‐embedded tissue was stained with polyclonal anti‐C4d antibody. Detection of donor‐specific antibody (DSA) was determined by flow cytometric assay. The cases were divided according to C4d positivity.

Results:  Three of 14 cases (21.4%) were C4d positive and belonged to the C4d+/DSA+ group, while 11 cases were of the C4d−/DSA− group. There were no significant differences between the two groups in serum creatinine (sCr) or proteinuria at the time of biopsy. A trend towards decreasing rate of the inverse of sCr (1/sCr) in the C4d+/DSA+ group was noted. In the C4d+/DSA+ group, three transplant glomerulopathy (TGP) were identified. On the other hand, TGP were identified in six of 11 cases of the C4d−/DSA− group. We investigated the relevance of typical chronic rejection (CR) features and the positivity of C4d. No significant differences were observed between the CR features and C4d depositions in PTC (p = 0.26).

Conclusion:  In long‐term survival cases with positive C4d, a trend towards decreasing rate of 1/sCr was revealed, but their histological characteristic features was not recognized.
Early recurrence of lupus nephritis after renal transplantation – a case report
Authors: Fujii Akiko , Yamaguchi Yutaka , Horita Shigeru , Yumura Wako , Fuchinoue Shouhei , Teraoka Satoshi
Published: June 2006

Abstract:  The risk of recurrent lupus nephritis (LN) in renal transplant recipients with systemic lupus erythematosus (SLE) used to be rare (1–4%). However, recent studies have suggested a higher rate of recurrence in SLE patients after renal transplantation (up to 30%). The interval from transplantation to recurrence of LN has been reported to vary from five days to eight years. We report here a renal transplant recipient with SLE who had recurrent LN 10 d after transplantation.
Protected areas in fisheries: a two‐patch, two‐species model*
Authors: Greenville Jared , MacAulay T. Gordon
Published: July 2006

The use of marine protected areas as a fishery management tool has been suggested as a hedge against management failures and variation in harvests. A stochastic bioeconomic model of a hypothetical predator–prey fishery is used to test the performance of protected areas in a fishery with heterogenous environments. Protected areas are analysed under density‐dependent and sink‐source dispersal relationships between the subpopulations that occur within the fishery. Differing management structures governing resource extraction are analysed. The focus of the study is placed on the biological and management characteristics that yield benefits to both fishers and society. It is shown that the establishment of a protected area improves fishery rent and lowers harvest variation. This result is sensitive to both current management controls and the correlation between species and patches.
Measuring risk attitude of agricultural producers using a mail survey: how consistent are the methods?
Authors: Fausti Scott , Gillespie Jeffrey
Published: July 2006

A mail survey is used to examine the consistency of alternative risk preference elicitation procedures using five commonly used methods. These elicitation procedures have been used in previous studies to characterise risk preference. Results show little consistency across procedures, supporting strength‐of‐preference studies. A general recommendation for mail surveys is the development of relatively easy‐to‐understand risk‐preference elicitation procedures that are framed according to the situational construct in question.
Towards the measurement of the impacts of improving research capacity: an economic evaluation of training in wheat disease resistance*
Authors: Brennan John P. , Quade Kathryn J.
Published: July 2006

It is notoriously difficult to assess the economic value of research aimed at improving research capacity, particularly for the human capital component of research capacity. In this paper, a framework is developed and an analysis is undertaken of the value of training for scientists in wheat rust resistance. The value of improving human capital is assessed through a framework based on marginal analysis of the improvement in productivity outcomes flowing from the increased capacity. On that basis, the value of programs to build human capacity through training or further education can be estimated. Although such estimates are necessarily qualified, they provide a basis for quantifying the value of building research and development capacity.
Temperature and leaf wetness duration affect phenotypic expression ofRlm6‐mediated resistance toLeptosphaeria maculansinBrassica napus
Authors: Huang Yong‐Ju , Evans Neal , Li Zi‐Qin , Eckert Maria , Chèvre Anne‐Marie , Renard Michel , Fitt Bruce D. L.
Published: July 2006

Near‐isogenicBrassica napuslines carrying/lacking resistance geneRlm6were used to investigate the effects of temperature and leaf wetness duration on phenotypic expression ofRlm6‐mediated resistance.

Leaves were inoculated with ascospores or conidia ofLeptosphaeria maculanscarrying the effector geneAvrLm6. Incubation period to the onset of lesion development, number of lesions and lesion diameter were assessed. Symptomless growth ofL. maculansfrom leaf lesions to stems was investigated using a green fluorescent protein (GFP) expressing isolate carryingAvrLm6.

L. maculansproduced large grey lesions on Darmor (lackingRlm6) at 5–25 °C and DarmorMX (carryingRlm6) at 25°C, but small dark spots and ‘green islands’ on DarmorMX at 5–20°C. With increasing temperature/wetness duration, numbers of lesions/spots generally increased. GFP‐expressingL. maculansgrew from leaf lesions down leaf petioles to stems on DarmorMX at 25°C but not at 15°C.

We conclude that temperature and leaf wetness duration affect the phenotypic expression ofRlm6‐mediated resistance in leaves and subsequentL. maculansspread down petioles to produce stem cankers.
Comparison of Risk Factors Between Prehypertension and Hypertension in Korean Male Industrial Workers
Authors: Lee Ji Hyun , Hwang Seon Young , Kim Eun Jeong , Kim Mi Ja
Published: June 2006

ABSTRACT
Objectives: To compare risk factors for prehypertension and hypertension in male industrial workers in Korea.

Sample: Participants included 2,476 males aged 19–56 years who were employed in an airplane manufacturing industry.

Methods: Health records of all subjects were analyzed during a biennial employee physical checkup that included a health survey questionnaire and blood tests.

Results: Forty‐six percent of subjects had prehypertension and 15% had hypertension. Multivariate logistic regression analysis showed that, after adjustment for age, workplace, and risk variables, subjects who were currently alcohol drinkers, in blue collar jobs, body mass index (BMI) ≥25 kg/m2, and had cholesterol ≥201 mg/dl were 1.30, 1.28, 1.27, and 1.21 times more likely to have prehypertension respectively, compared with normotensives. Subjects with FBS≥121 mg/dl, BMI≥25 kg/m2, and age≥40 years were 2.47, 1.52, and 1.36 times more likely to have hypertension respectively, compared with prehypertensive subjects.

Conclusions: Nurses working in the industrial sector should focus on education and counseling regarding the risk factors for prehypertension and hypertension, and they should emphasize the importance of healthy lifestyles and curbing obesity to help arrest the progression of prehypertension to hypertension.
Teaching Emergency Preparedness to Restricted‐Budget Families
Authors: Mack Shannon E. , Spotts Daniel , Hayes Atraya , Warner Joanne Rains
Published: June 2006

ABSTRACT
Objectives: To fulfill the health teaching and promotion responsibilities of public health nurses, a teaching intervention was devised to prepare low‐income, low‐resource families to survive a worst‐case disaster scenario. The purpose of this study is to introduce that plan.

Design: Teaching sessions were held to increase awareness about disaster preparedness and to provide the resources necessary for preparing disaster kits on a restricted budget.

Sample: This project focused on families enrolled at the Children's Relief Nursery in Portland, Oregon's St. Johns District.

Measurements: Posttest assessments and client follow‐up at 3, 6, and 12 months were used to assess the effectiveness of the curriculum and follow‐through on kit preparation.

Results: A replicable teaching tool was successfully developed, and the interest and commitment of community partners dedicated to assisting restricted‐budget families was secured.

Conclusions: States' disaster plans hinge on individuals' implementation of their own survival plans, and it is vital that these individuals be made aware of their responsibility. It is truly a matter of life and death that families possess the skills, knowledge, and resources to carry out a disaster survival plan successfully, and it is the ethical responsibility of the public health nurse to intervene.
A Validation and Potential Modification of the Pneumonia Severity Index in Elderly Patients with Community‐Acquired Pneumonia
Authors: Naito Tateaki , Suda Takafumi , Yasuda Kazumasa , Yamada Takashi , Todate Akihito , Tsuchiya Tomoyoshi , Sato Jun , Chida Kingo , Nakamura Hirotoshi
Published: July 2006

OBJECTIVES: To evaluate the discriminatory power of the Pneumonia Severity Index (PSI) in elderly patients with community‐acquired pneumonia (CAP) and to improve its performance.

DESIGN: Retrospective review of 193 patients from 1999 to 2001 to derive prognostic rules. The rules were prospectively validated in 144 patients from 2002 to 2003.

SETTING: Iwata City Hospital, a 400‐bed general hospital.

PARTICIPANTS: Patients aged 80 and older who had CAP and were admitted to the hospital.

MEASUREMENTS: Predictors of 30‐day mortality were identified using logistic regression analysis, and several rules were constructed by combining the PSI and the independent predictors. Classification and regression tree analysis was also used for constructing rules. Sensitivity and specificity were calculated.

RESULTS: The original PSI, which defines PSI Class IV and V as a high‐risk group, did not perform well in discriminating survivors from nonsurvivors (sensitivity 100%, specificity 15%), whereas a modified PSI, which defines only PSI Class V as a high‐risk group, performed better (sensitivity 86%, specificity 63%). Three predictors for mortality were identified independent from the modified PSI: performance status (PS) Grade 3 or higher, anorexia, and partial pressure of carbon dioxide of 50 mmHg or greater. By combining the modified PSI and PS, the performance could be further improved (sensitivity 79%, specificity 80%).

CONCLUSION: The modified PSI could identify low‐risk patients more accurately than the original PSI. In addition, by combining the modified PSI with PS, higher performance was obtained. Such information would aid physicians in clinical decision‐making without overestimating the risk for elderly patients with CAP.