bluuebunny/crossref_metadata_2025 huggingface dataset:
miR172 regulates stem cell fate and defines the inner boundary of APETALA3 and PISTILLATA expression domain in Arabidopsis floral meristems
Authors: Zhao Li , Kim YunJu , Dinh Theresa T. , Chen Xuemei
Published: June 2007

In Arabidopsis, two floral homeotic genes APETALA2 (AP2) and AGAMOUS (AG) specify the identities of perianth and reproductive organs, respectively, in flower development. The two genes act antagonistically to restrict each other to their proper domains of action within the floral meristem. In addition to AG, which antagonizes AP2, miR172, a microRNA, serves as a negative regulator of AP2. In this study, we showed that AG and miR172 have distinct functions in flower development and that they largely act independently in the negative regulation of AP2. We uncovered functions of miR172‐mediated repression of AP2 in the regulation of floral stem cells and in the delineation of the expression domain of another class of floral homeotic genes. Given the antiquity of miR172 in land plants, our findings have implications for the recruitment of a microRNA in the building of a flower in evolution.
Donor‐specific antibody in chronic rejection is associated with glomerulopathy, thickening of peritubular capillary basement membrane, but not C4d deposition
Authors: Miura Masayoshi , Ogawa Yayoi , Kubota Kanako C. , Harada Hiroshi , Shimoda Naohiko , Ono Takenori , Morita Ken , Watarai Yoshihiko , Hirano Tetsuo , Nonomura Katsuya
Published: June 2007

Abstract:  The impact of post‐transplant donor‐specific antibody (DSA) on the development of chronic rejection has been focused recently. The aim of this study was to evaluate the significance of DSA, graft function and pathological factors of chronic rejection. Seventy‐three kidney recipients who underwent protocol biopsy were included in the study. The median follow‐up period after transplant was 40 months. The presence of anti‐HLA antibody (aHLAAb) and DSA was tested using flow beads analysis (FlowPRA®). The patients were divided into a group with DSA, a group with non‐donor‐specific aHLAAb and a group without aHLAAb. Protocol biopsy specimen were compared for transplant glomerulopathy (cg), vasculopathy (cv), C4d deposition at peritubular capillary (PTC), peritubular capillaritis (ptc score 0–3) and thickening of PTC basement membrane (ptcbm score 0–3) as recently proposed. The presence of DSA was significantly associated with the presence of cg, ptcbm. The group with non‐donor‐specific aHLAAb had ptcbm but did not have cg. The group without aHLAAb rarely showed ptcbm. The presence of DSA was associated with impaired graft function. C4d was not specific for the patients with DSA. These histopathological markers are useful in the detection of immunological chronic rejection. Early detection by screening tests will be important for treatment before irreversible change occurs.
The difference in histopathology of antibody‐mediated rejection between ABO incompatible and pre‐sensitized cases
Authors: Shimoda Naohiko , Miura Masayoshi , Kubota Kanako C , Hotta Kiyohiko , Iwami Daiki , Itoh Tomoo , Morita Ken , Watarai Yoshihiko , Nonomura Katsuya
Published: June 2007

Abstract:  Suppression of antibody‐mediated rejection (AMR) is mandatory for the acceptance of renal allograft in ABO blood type incompatible and pre‐sensitized combinations. The aim of this study was to evaluate the difference in histopathology of AMR between ABO incompatible (ABOI) and pre‐sensitized cases. Among 69 kidney recipients who underwent transplant surgery at our institute since 2002, four patients who manifested AMR were included in this study. They initially received quadrant immunosuppressants, tacrolimus, mycophenolate mofetil, methylprednisolone and basiliximab. Two patients received grafts from ABOI donors and the other two received grafts from flow T‐cell crossmatch‐positive donors. Although satisfying antibody removal was achieved by pre‐transplant plasmapheresis, all four cases manifested acute AMR, within two wk post‐transplant. Antibody titer and panel reactive antibody increased at the time of AMR. ABOI cases showed slight cellular infiltration. These cases showed diffuse, strong and linear deposition of C4d at peritubular capillaries (PTC). On the other hand, pre‐sensitized cases showed more intense cellular infiltration, especially in glomerulus but only faint and focal deposition of C4d at PTC. All four cases were treated with corticosteroid pulse therapy in conjunction with several sessions of plasmapheresis.
A case of nephrotic syndrome 11 yr post‐kidney transplantation
Authors: Nishi S. , Imai N. , Nakamura G. , Ueno M. , Kawamura K. , Kaneko Y. , Goto S. , Alchi B. , Saito K. , Takahashi K. , Gejyo F.
Published: June 2007

Abstract:  We present here a male patient who had developed nephrotic syndrome 11 yr after kidney transplantation. Nephrotic syndrome suddenly occurred after severe sunburn he got in Hawaii. Such a clinical course seemed very rare in kidney transplantation, and multifactorial etiology was suspected. The histological findings of graft biopsy were intricate. On light microscopy, there were mesangial expansion and endocapillary proliferation with duplication of GBM and crescent formation. Deposits of IgM in mesangium were the most prominent finding on immunofluorescence microscopy, but IgA and C3 deposits were also detected. Electron microscopy revealed paramesangial and a few subepithelial dense deposits. Additionally, small organized deposits were found in the subepithelial space. Based on these findings, a provisional diagnosis of IgA nephropathy superimposed on chronic transplant glomerulopathy was made. However, hepatitis C virus related nephropathy could not be excluded.
Recurrence of Henoch–Schönlein purpura nephritis superimposed on severe pre‐eclampsia in a kidney transplant patient
Authors: Tanno Yudo , Yamamoto Hiroyasu , Yamamoto Izumi , Yaginuma Tatsuhiro , Mitome Jun , Kawamura Yoshimi , Miyazaki Yoichi , Yokoyama Keitaro , Utsunomiya Yasunori , Yamaguchi Yutaka , Hosoya Tatsuo
Published: June 2007

Abstract:  Henoch–Schönlein purpura nephritis (HSPN) frequently recurs in patients following kidney transplantation, and pregnancy has been reported to be an exacerbating factor. However, little is known about the recurrence of HSPN during pregnancy in patients with superimposed pre‐eclampsia having excellent graft function who had experienced kidney transplantation. Here, we report a case of recurrent HSPN complicating severe pre‐eclampsia six yr after transplantation. A 31‐yr‐old woman who had received a living‐related kidney transplant at age 25 became pregnant. The cause of her end‐stage renal disease was biopsy‐proven HSPN. She had an excellent clinical course after transplantation, with good allograft function (serum creatinine <0.9 mg/dL, no proteinuria or hematuria, no episode of rejection), and normal blood pressure. We discontinued the angiotensin II receptor blocker that had been prescribed to prevent glomerular hyperfiltration. After week 17 of pregnancy, proteinuria and blood pressure increased markedly, and then her kidney function deteriorated progressively with intermittent mild microhematuria. At week 28 of pregnancy, umbilical blood flow and fetal growth were impaired, prompting preterm cesarean delivery. Subsequently, her blood pressure and serum creatinine normalized immediately, although the urinary protein excretion decreased insufficiently from 6.0 to 1.0 g/d at six months postpartum. In general, hematuria has a predictive value for the recurrence of HSPN. Clinically, we considered this case to be superimposed pre‐eclampsia, not recurrent HSPN. However, a biopsy conducted seven months postpartum suggested recurrent HSPN on her renal allograft. In addition, focal segmental membranous nephropathy with C1q deposition was observed. It was difficult to determine when the HSPN and membranous lesions occurred. This case suggests that a pathological evaluation is important in HSPN patients after transplantation to reduce adverse risks during and after pregnancy.
A case of massive kidney graft calcification that developed early in a child recipient with hyperparathyroidism
Authors: Kanetsuna Yukiko , Hisano Masataka , Miura Kenichiro , Tanaka Eriko , Hattori Motofumi , Teraoka Satoshi , Yamaguchi Yutaka
Published: June 2007

Abstract:  A boy aged six yr and six months with end‐stage renal disease because of focal segmental glomerulosclerosis underwent cadaveric renal transplantation. Ischemic injury during the operation resulted in a severely dysfunctional graft. A renal graft biopsy was performed on post‐operative day (POD) 21. The biopsy specimen showed the presence of many intratubular calcium crystals, patchy tubular injury, and focal aggressive tubulointerstitial rejection. Pelvic computed tomography performed on POD 23 also showed prominent calcification in and around up to two‐thirds of the graft. After the biopsy, the graft function recovered, and hemodialysis was stopped on POD 22. A second graft biopsy was performed on POD 52. This biopsy specimen showed recovery from rejection, although the nephrocalcinosis remained. It was suggested that secondary hyperparathyroidism and hyperphosphatemia provoked nephrocalcinosis in this patient.
A case of ABO‐incompatible renal transplantation with smoldering antibody‐mediated rejection that led to chronic vascular rejection 14 months after transplantation
Authors: Fujii Akiko , Yamaguchi Yutaka , Horita Shigeru , Tanabe Kazunari
Published: June 2007

Abstract:  A 55‐year‐old female patient with chronic renal failure received an ABO‐incompatible secondary renal transplantation from her husband. She had positive pre‐operative flow panel reactive antibody reactivity to classes I and II. Donor‐specific antibody (DSA) was also positive in classes I and II. She was treated with rituximab, plasma exchange, and splenectomy before transplantation. The serum creatinine (sCr) level rose to 1.26 mg/dL on post‐operative day (POD) 17, and the episode graft biopsy specimen was diagnosed as mild acute vascular rejection. On POD 31, the protocol biopsy showed mild transplant glomerulitis and peritubular capillaritis (ptc2) with positive C4d, suggestive of antibody‐mediated rejection (AMR). She had cytomegalovirus (CMV) infection and was treated with ganciclovir. When the sCr rose to 1.7 mg/dL, two months post‐operatively, the episode biopsy showed mild AMR and no evidence of CMV infection. Since then, no clinical evidence of rejection has been observed, but protocol biopsy specimens obtained six and nine months postoperatively showed histologic findings suggestive of smoldering, persistent AMR. The patient was treated with deoxyspergualin and steroid pulse therapy after each protocol biopsy. Fourteen months after her operation, the protocol biopsy specimen revealed chronic allograft nephropathy with chronic rejection. It showed sclerosing vasculopathy with neomedia formation in the interlobular arteries and mild thickening of the peritubular capillary basement membrane with ptc1. DSA was not detected post‐operatively. With strategies using recently available immunosuppressive agents, the long‐term survival rate of renal grafts does not differ between ABO‐incompatible and ABO‐compatible cases. Anti‐human leukocyte antigen (HLA) antibody may have been the cause of smoldering AMR and consequent chronic rejection in this case. Further research is needed to devise a more successful desensitization regimen for organ transplantation in highly sensitized recipients.
HLA‐A*68020103 shows an eight nucleotides deletion within intron 2 but has normal mRNA splicing and serological recognition
Authors: Balas A. , Sánchez‐García F. , Bustamante L. , García‐Sánchez F. , Vicario J. L.
Published: June 2007

A novel A*68020103 allele was completely characterized by sequencing in a Spanish bone marrow donor. A*68020103 has an eight nucleotides deletion at the 5′‐end of intron 2, when compared with other A*6802 alleles. This alteration does not affect either its mRNA splicing process or serological detection.
Analysis of HLA class I–II haplotype frequency and segregation in a cohort of patients with advanced stage ovarian cancer
Authors: Gamzatova Z. , Villabona L. , Van Der Zanden H. , Haasnoot G. W. , Andersson E. , Kiessling R. , Seliger B. , Kanter L. , Dalianis T. , Bergfeldt K. , Masucci G. V.
Published: June 2007

In solid tumors, human leucocyte antigen (HLA)‐A2 has been suggested to be a risk factor and a negative prognostic factor. The HLA‐A2 allele in Scandinavia has a high prevalence; it decreases with latitude and also with ovarian cancer mortality in Europe. Furthermore, an association of the HLA‐A2 allele with severe prognosis in serous adenocarcinoma of the ovary in stages III–IV was found. Thirty‐two unrelated Swedish women with relapsing or progressive ovarian cancer were analysed for the genotypes at the HLA‐A, HLA‐B, HLA‐Cw, and HLA‐DRB1 loci by the polymerase chain reaction/sequence–specific primer method. The frequencies of HLA alleles of healthy Swedish bone marrow donors provided by the coordinating centre of the Bone Marrow Donors Worldwide Registries, Leiden, the Netherlands were used as controls. When this cohort of epithelial ovarian cancer patients was compared with healthy Swedish donors, the frequency of HLA‐A1 and HLA‐A2 gene/phenotype appears, although not statistically significant, to be increased in patients with ovarian carcinoma, while HLA‐A3 was decreased. HLA‐A2 homozygotes were twofold higher in patients. The A2‐B8 haplotype was significantly increased (corrected P value). A2–B5, A2–B15, A2–DRB1*03, A2–DRB1*04, A2–B15–Cw3, and A2–B8–DRB1*03 had odds ratio as well as the level of the lower confidence interval above 1 and significant P value only when considered as single, non‐corrected analysis. HLA‐B15 and HLA‐Cw3 were only present in HLA‐A2‐positive patients showing that the HLA‐A2–HLA‐Cw3 and HLA‐B15 haplotypes were segregated. In this selected cohort with advanced disease, there are indications of an unusual overrepresentation of HLA class I and II genes/haplotypes as well as segregation for the HLA‐A2–HLA‐Cw3 and HLA‐B15 haplotypes. These findings are presented as a descriptive analysis and need further investigations on a larger series of ovarian cancer patients to establish prognostic associations.
The MHC2TA−168A/G and +1614G/C polymorphisms and risk for multiple sclerosis or chronic inflammatory arthropathies
Authors: O’Doherty C. , Hawkins S. , Rooney M. , Vandenbroeck K.
Published: June 2007

The −168A‐G polymorphism has been shown to influence transcription of the MHC2TA gene and has been implicated in several inflammatory/autoimmune disorders. Attempts to reproduce these findings have been inconclusive. We investigated the role of this promoter single nucleotide polymorphism (SNP) in 440 multiple sclerosis (MS), 293 rheumatoid arthritis (RA), 74 juvenile idiopathic arthritis (JIA) patients and 316 healthy controls from Northern Ireland. We also genotyped a non‐synonymous SNP in exon 11, +1614G/C. There was no significant difference in the −168G allele frequencies and carriage rates in the separate RA, JIA, or MS collections compared with the control group [odds ratio (OR) = 1.1, 95% confidence intervals (CI) = 0.86–1.44; OR = 1.1, 95% CI = 0.75–1.68; OR = 1.1, 95% CI = 0.84–1.35, respectively]. Assessment of the common phenotype (chronic inflammatory disease; n = 807 vs 316 controls) was negative as well. Carriage of +1614C was protective against JIA (OR = 0.6, 95% CI = 0.3–1.0) and showed a similar trend in RA and MS (OR = 0.7, 95% CI = 0.5–1.0; OR = 0.8, 95% CI = 0.6–1.0, respectively). The common phenotype (chronic inflammatory disease) was also significant (OR = 0.7, 95% CI = 0.6–1.0).
Analysis of the HFE gene (C282Y, H63D and S65C) mutations in a general Chinese Han population
Authors: Lin A. , Yan W. H. , Xu H. H. , Zhu M. , Zhou M. Y.
Published: June 2007

Hereditary hemochromatosis (HH) is one of the most common autosomal recessive genetic disorders of iron metabolism in white populations, which leads to inappropriately high iron absorption. C282Y, H63D, and S65C are three major missense mutations of the hemochromatosis gene (HFE). In the present study, C282Y, H63D, and S65C mutations in 395 normal Chinese Han populations from Zhejiang province were investigated. No C282Y, S65C mutations, and H63D homozygote was observed, while the genotype frequency of H63D heterozygote was 4.6% and the allelic frequency 2.3% in this population. This was the first report to analyze the prevalence of C282Y, H63D, and S65C mutations in the HFE gene in a Chinese Han population. Low incidence of the HFE gene mutations could be a reason for the rarity of HH in the Chinese Han population studied.
HLA‐associated genetic resistance and susceptibility to type I diabetes in French North Africans and French natives
Authors: Guérin V. , Léniaud L. , Pédron B. , Guilmin‐Crépon S. , Tubiana‐Rufi N. , Sterkers G.
Published: June 2007

The distribution of human leukocyte antigen (HLA)‐DRB1–DQA1–DQB1 haplotypes was analyzed separately in two distinct French ethnic groups with type I diabetes (T1D), i.e. French North African migrants (n= 64, mean age at diagnosis = 8.25 years) and ancient French natives (n= 60, mean age at diagnosis = 7.42 years). HLA associations were determined by calculating odds ratios (ORs) between patients and two ethnic‐matched control populations. Results show highly similar ORs for the conservative DRB1*0301–DQA1*0501–DQB1*0201 haplotype of susceptibility (OR: 3.22 and 3.93 in migrants and natives, respectively) and the DRB1*1501–DQA1*0102–DQB1*0602 haplotype of resistance (OR: 0.05 and 0.03, respectively). In contrast, among the more variable DRB1*04–DQB1*0302 haplotypes of susceptibility, the DRB1*0402 (OR: 3.10 and 32.84) and 0405 (OR: 5.90 and 16.25, respectively) were associated with T1D in migrants and natives, whereas an increase of DRB1*0401, a rare allele in migrants, was significant in natives only. Also, among the DRB1*11–DQA1*0505–DQB1*0301 haplotypes of resistance, the OR observed for DRB1*1104–DQA1*0505–DQB1*0301, common in migrants, was lower (OR: 0.08) than for DRB1*1101–DQA1*0505–DQB1*0301 (OR: 0.32), common in natives. How DRB1*11 subtypes might affect differently the risk conferred by DQA1*0505–DQB1*0301 will be discussed.
Analysis of BTNL2 genetic polymorphisms in British and Dutch patients with sarcoidosis
Authors: Spagnolo P. , Sato H. , Grutters J. C. , Renzoni E. A. , Marshall S. E. , Ruven H. J. T. , Wells A. U. , Tzouvelekis A. , Van Moorsel C. H. M. , Van Den Bosch J. M. M. , Du Bois R. M. , Welsh K. I.
Published: June 2007

Sarcoidosis is a heterogeneous disorder, both phenotypically and genetically. Two independent studies have recently shown that a functional polymorphism within butyrophilin‐like 2 (BTNL2) gene predisposes to sarcoidosis independently of the human leukocyte antigen (HLA)‐DRB1 alleles. However, in both studies, data analysis was not stratified by Löfgren’s syndrome, a clinically and genetically distinct sarcoidosis subset. BTNL2, potentially encoding an immune coreceptor, is adjacent and in linkage disequilibrium (LD) with HLA‐DRB1. We investigated six BTNL2 variants, including the functional rs2076530 (G > A), as well as HLA‐DRB1 alleles, by sequence‐specific primers–polymerase chain reaction, in 288 patients and 446 controls from two European countries. In the patient group as a whole, the HLA‐DRB1*14 [odds ratio (OR) = 3.1, Pc = 0.0003], DRB1*12 (OR = 2.5, Pc = 0.003), and BTNL2 rs2076530 A allele (OR = 1.49, Pc = 0.002) were all associated with disease susceptibility. However, after exclusion of patients presenting with Löfgren’s syndrome and after adjusting for HLA‐DRB1 alleles, the association between BTNL2 rs2076530 A and disease disappeared (P = 0.23). By contrast, both HLA‐DRB1*14 and DRB1*12 remained strongly significant (OR = 3.60, P < 0.0001 and OR = 3.03, P = 0.003, respectively). BTNL2 haplotype 4, tagged by the rs2076530 G allele, also remained associated with non‐Löfgren sarcoidosis after adjusting for HLA‐DRB1 alleles (OR 0.37, P = 0.016). In summary, HLA‐DRB1*14, DRB1*12, and BTNL2 haplotype 4 – but not rs2076530 A – are associated with non‐Löfgren sarcoidosis. However, the tight LD across the HLA complex makes it difficult to identify the precise location of the susceptibility locus/i. Larger sample sets from different ethnic groups, finer mapping, and more robust LD analyses across the HLA region are needed.
KIR3DL2: diversity in a hematopoietic stem cell transplant population
Authors: Gedil M. A. , Steiner N. K. , Hurley C. K.
Published: June 2007

Exons 2 through 9 of KIR3DL2 were amplified from genomic DNA from 79 bone marrow transplantation patients and their unrelated donors. Sequencing of heterozygotes and isolated alleles identified 9 of the 17 known alleles. The alleles provide confirmation of previously submitted sequences and are carried by transformed B‐cell lines that can be used as references for assay development. Alleles 3DL2*001, *002, *007 and *009 accounted for 111 of the total 144 possible alleles and were the only ones found in a homozygous state. New alleles (3DL2*017, *018, *019, *020, and *021) were found in seven transplant samples and one workshop cell. This study describes the development of reagents and protocols for sequencing of KIR3DL2 alleles from genomic DNA.
Analysis of interleukin‐23 receptor (IL23R) gene polymorphisms in systemic lupus erythematosus
Authors: Sánchez E. , Rueda B. , Callejas J. L. , Sabio J. M. , Ortego‐Centeno N. , Jimenez‐Alonso J. , López‐Nevot M. A. , Martín J.
Published: June 2007

The aim of this study was to evaluate the association between systemic lupus erythematosus (SLE) and polymorphisms in the interleukin‐23 receptor (IL23R) gene, which have been previously found to be associated with two autoimmune diseases: inflammatory bowel disease and psoriasis. Our study includes 224 SLE patients and 342 healthy controls. The genotyping of IL23R variants was carried out using a polymerase chain reaction system with predeveloped TaqMan allelic discrimination assays. No statistically significant differences were observed between SLE patients and healthy controls with any of the IL23R genetic variants. In addition, we did not find any significant differences when we stratified SLE patients according to their clinical and demographic features. These results suggest that IL23R polymorphisms do not appear to play an important role in the susceptibility or severity of SLE in the Spanish population.
A novel hybrid allele (B*3563) originated from B*350101 and B*4001‐like alleles
Authors: Lee K. W.
Published: June 2007

The B*3563 showed a hybrid sequence carrying B*4001‐like sequence (exon 2) on B*350101 background.
Identification of a novel allele HLA‐A*9206 by sequence‐based typing in the Chinese population
Authors: Zhu F.‐M. , He J.‐J. , Yan L.‐X
Published: June 2007

A novel human leukocyte antigen‐A*9206 allele was identified by sequence‐based typing in China.
Cyclosporine monitoring in the early post‐transplant period in pediatric liver transplant recipients
Authors: Frauca E. , Diaz M. C. , De La Vega A. , Hierro L. , Camarena C. , Bartolo G. Muñoz , Díez R. , Murcia J. , Gámez M. , Peinado C. Sanchez , Santamaría M. López , Andrés I. , Jara P.
Published: June 2007

Abstract:  Monitoring of CsA blood levels two h post‐dose (C2) has shown a higher correlation to drug exposure than monitoring of trough levels (C0) at least in adults, but initial doses and target blood levels of CsA have yet to be established in pediatric transplant patients. The objectives of the study were to describe the pharmacokinetics of CsA administered by NGT in the first days after transplantation and the dose of Sandimmun Neoral® required to achieve minimum therapeutic range blood levels. This study included 20 pediatric liver transplant recipients (mean age of 3.2 yr) treated with CsA administered by NGT from day one post‐transplant until they were able to ingest oral medication. The study was continued until one yr of post‐transplant follow‐up. Eight h pharmacokinetic profiles were performed on days one, three, and five post‐transplant to determine the minimum dose required to achieve the therapeutic range. All children received an initial dose of 15 mg/kg/day of CsA by NGT. Mean CsA doses administered on days one, three, and five were 16.8, 29.5, and 36.5 mg/kg/day, respectively. Mean C0 levels of 119, 310, and 337 ng/mL and mean C2 levels of 213, 753, and 888 ng/mL were obtained. No correlation was found between C0 and C2 levels and the AUC0–8 h. Intravenous administration of CsA was required in 55% of patients. The biopsy‐confirmed acute rejection rate was 45%, with graft and patient survival rates of 95 and 100%, respectively. Conclusions: Poor absorption of CsA in small children requires a considerable increase in dose. CsA exposure cannot be estimated by single C0 or C2 determinations in the early post‐transplant period.
Italian experience of pediatric liver transplantation
Authors: Guariso Graziella , Visonà Dalla Pozza Laura , Manea Silvia , Salmaso Laura , Lodde Veronica , Facchin Paola ,   SIGENP Group of Liver Transplantation
Published: June 2007

Abstract:  The SIGENP Group has created an Italian Liver Transplantation database. The study considers all patients under 18 yr of age on the waiting list or transplanted between 1984 and 2005. Demographic and clinical data were collected and a descriptive analysis was conducted. Kaplan–Meier survival curves were calculated and Cox’s proportional‐hazards regression analysis were performed to identify predictors of death after transplantation. Twenty‐two Italian centers took part and data were collected on 622 cases: only 53.8% of the transplants performed up until 1998 were carried out in Italy, while this was true of 97.7% of the operations performed between 1999 and 2005. Recipient survival curve analysis revealed one‐, two‐ and five‐yr survival rates of 88, 87 and 84%, respectively, and a significant improvement in survival after 1998 (p = 0.0322). Cox’s analysis identified the following risk factors for death after liver transplantation, i.e. transplantation before 1998, neoplasms or fulminant hepatic failure as indications, being in intensive care at the time of transplantation and retransplantation. The center where the transplant is performed also revealed an influence on patient survival. Thanks to a better patient follow‐up and more cooperation between specialists, the mean survival after liver transplantation is improving and Italian children can be transplanted in Italy.
A pediatric case of transfusion‐related acute lung injury following bone marrow infusion
Authors: Yui Yoshihiro , Umeda Katsutsugu , Kaku Haruna , Arai Masato , Hiramatsu Hidefumi , Watanabe Ken‐ichiro , Saji Hiroh , Adachi Souichi , Nakahata Tatsutoshi
Published: June 2007

Abstract:  TRALI is a rare but serious complication associated with transfusion, and known to occur following infusion of all types of plasma‐containing blood products. However, only one adult case of TRALI after allogenic marrow graft has been reported. In this study, we present a pediatric case possibly associated with allogenic marrow infusion. A 10‐yr‐old girl was referred to our hospital for the treatment of acute myeloid leukemia. She underwent allogenic bone marrow transplantation from her HLA‐2‐loci‐mismatched mother. During conditioning, she suffered from bacterial sepsis, but it had improved with antibiotics until day 0 of transplantation. Two h after starting the marrow infusion, she developed severe hypoxia. We discontinued the infusion and started steroids, which improved her respiratory condition. However, she developed respiratory failure again after resuming infusion of the graft. Despite intensive care with mechanical ventilation, the patient died of endotoxin shock five days after transplantation. Although we could not identify the antibody which might have been involved in the respiratory distress, the clear temporal relationship between marrow infusion and respiratory distress suggested that similar acute lung injury to TRALI might have occurred following allogenic marrow infusion in the present case.
Tc‐99m DTPA renography in children following renal transplantation – Its value in the evaluation of rejection
Authors: Sundaraiya S. , Mendichovszky I. , Biassoni L. , Sebire N. , Trompeter R. S. , Gordon I.
Published: June 2007

Abstract:  A retrospective analysis of the value of Tc‐99m DTPA DRS in children requiring renal biopsy following transplantation. Thirty‐one children following renal transplantation with possible rejection underwent thirty‐nine DRS and biopsy within a 72‐h period and clinical followed up for 12 months. The biopsy was classified according to the Banff 97. The DRS assessed semi‐quantitatively images of renal perfusion and filtration, and the balance between these two images. The clinical notes were reviewed. Based on the biopsy results 15 children had acute rejection, three children chronic rejection, nine children a mixed appearance of both acute and chronic rejection while 12 children had no rejection. Based on the long‐term clinical outcome, the DRS had an overall sensitivity of 76% and specificity of 86%. While renal biopsy remains the gold standard for the diagnosis of rejection, if the perfusion and filtration phases of the DRS are analysed separately and the results integrated, there is a possibility of suggesting that acute rejection is not the cause of the increase in creatinine. The DRS provides useful information to the nephrologist when taken in conjunction with the biopsy result and other investigations.
No evidence of PERV infection in healthcare workers exposed to transgenic porcine liver extracorporeal support
Authors: Levy Marlon F. , Argaw Takele , Wilson Carolyn A. , Brooks James , Sandstrom Paul , Merks Harriet , Logan John , Klintmalm Goran
Published: June 2007

Background:  Clinical xenotransplantation holds great promise by providing one solution to the shortage of human organs for transplantation, while also posing a potential public health threat by facilitating transmission of infectious disease from source animals to humans. One potential vector for infectious disease transmission is healthcare workers (HCW) who are involved in administering xenotransplantation procedures. Methods:  In this study, we studied 49 healthcare workers involved in the care of two subjects who participated in a study of porcine liver perfusion as treatment of fulminant hepatic failure. We looked for serologic and virologic evidence of transmission of porcine endogenous retrovirus, and found that HCW had no evidence of infection. Conclusions: Results of our survey demonstrate that application of standard precautions may be sufficient to prevent transmission of porcine endogenous retrovirus, an agent of concern in ex vivo xenotransplantation products.
Effect of various immunosuppressive monotherapies on survival and histopathology of monkey islet xenografts in rats
Authors: Balamurugan A. N. , Nelson Everette J. R. , Ramakrishna Banumathi , Gunasekaran S.
Published: June 2007

Abstract:  Background:  The isolation and testing of monkey islets after transplantation in small animal models provides basic information about their functional capacity. We describe the effect of cyclosporine A (CsA), tacrolimus (FK506) or prednisolone monotherapy on preventing monkey islet graft rejection after xenoTx in a rat model. Histopathological aspects are reported.

Methods:  Indian bonnet monkey (Macaca radiata radiata) islets were isolated by a simple stationary digestion technique using collagenase. The islets were purified with dextran density gradients and were transplanted under the renal capsule of normal or diabetic rats. The rats received a daily dose of CsA, or FK506, or prednisolone, and the grafts were removed at different intervals to determine islet survival. The effect of discontinuation of CsA on islet graft survival was also monitored. Histological examination of islets transplanted into normal or streptozotocin‐induced diabetic rats was carried out. In diabetic rats, islet survival was determined by the graft’s ability to achieve euglycemia.

Results: Reversal of diabetes was achieved in all transplanted diabetic rats, demonstrating the efficacy of the isolated monkey islets. Histological examination indicated that monkey islets survived in the presence of continuous high‐dose immunosuppressive monotherapy in rats. Various types of infiltrating cells were observed in the grafted area at varying times after transplantation, depending on the immunosuppressive treatment. After discontinuation of CsA, the grafts were protected for a short period.

Conclusions:  This study provided evidence for monkey islet survival after transplantation into rats receiving immunosuppressive monotherapy. Basic information on infiltrating cell types may be important in the study of xenograft rejection.
Soluble Galα(1,3)Gal conjugate combined with hDAF preserves morphology and improves function of cardiac xenografts
Authors: Brandl Ulrike , Erhardt Matthias , Michel Sebastian , Jöckle Hannah , Burdorf Lars , Bittmann Iris , Rössle Matthias , Mordstein Volker , Brenner Paolo , Hammer Claus , Reichart Bruno , Schmoeckel Michael
Published: June 2007

Abstract:  Background:  Cytotoxic anti‐Galα(1,3)Gal antibodies play a key role in the rejection of pig organs transplanted into primates. Regimens reducing anti‐Galα(1,3)Gal antibodies were associated with severe side effects unable to prevent antibody rebound until soluble synthetic oligosaccharides with terminal Galα(1,3)Gal inhibiting antigen binding became available. We displayed kinetics of anti‐pig and anti‐Galα(1,3)Gal IgM and IgG antibody levels using GAS914, a Galα(1,3)Gal trisaccharide conjugated to poly‐l‐lysine, and investigated corresponding changes of parameters of heart function. Methods:  Using a working heart model, hDAF pig hearts were perfused with human blood containing GAS914 (group 1). As controls hDAF pig hearts (group 2) and landrace pig hearts (group 3) were perfused with human blood only. Levels of anti‐Galα(1,3)Gal (IgM, IgG) and anti‐pig antibodies were assessed to prove the effectiveness of GAS914. As parameters of heart function, cardiac output (CO), stroke work index (SWI), coronary blood flow (CBF) and coronary resistance were measured. Creatine phosphokinases, lactate dehydrogenase and aspartate aminotransferase were evaluated as markers of myocardial damage. Histological and immunohistochemical investigations were performed at the end of perfusion. Results: In group 1 an immediate and extensive reduction in both IgM and IgG anti‐Galα(1,3)Gal was found. Anti‐pig antibodies were eliminated accordingly. Antibody binding to GAS914 was complete before the start of organ perfusion. Corresponding to rapid antibody elimination in group 1 GAS914 not only was able to significantly prolong the beating time of the heart in hDAF pigs, but also to clearly improve functional parameters. When switching to the working heart mode hDAF pig hearts perfused with human blood containing GAS914 (group 1) revealed a CO starting at a significantly higher level than hDAF (group 2) and non‐transgenic pig hearts (group 3) perfused with human blood only. Similarly, in group 1 SWI was significantly increased at the beginning of perfusion compared to that of group 2 and group 3. The increase in CBF during perfusion and the corresponding fall of coronary resistance occurred without significant differences between the groups revealing the independence of hDAF and GAS914. Conclusions: Due to an immediate and profound reduction in Galα(1,3)Gal‐specific antibodies, soluble Galα(1,3)Gal conjugates not only prolong survival, but also improve the hemodynamic performance of the heart in DAF pigs.
Delayed functional maturation of neonatal porcine islets in recipients under strict glycemic control
Authors: Kin Tatsuya , Korbutt Gregory S.
Published: June 2007

Abstract:  Background:  The aim of this study was to compare the functional maturation of neonatal porcine islet (NPI) grafts exposed to long‐term hyperglycemia with those implanted under euglycemic conditions.Methods:  mice Neonatal porcine islets were transplanted under the left renal capsule of diabetic SCID mice (group H), or in diabetic SCID mice who were also implanted with 500 BALB/c islets under the right renal capsule (group N). On day 42, the right kidneys were removed in both groups. Results:  No animals in group H achieved euglycemia within 3 weeks after transplantation. Thus, these mice were exposed to long‐term hyperglycemia. Mice in group N became euglycemic immediately after transplantation, however after removal of BALB/c grafts on day 42 they exhibited significantly higher blood glucose levels than in group H and showed glucose intolerance after glucose administration. Cellular insulin content of NPI grafts harvested on day 58 or 72 was significantly lower in group N mice compared to group H. Conclusions:  These results suggest that tight control of glycemia reduces the functional maturation of NPI grafts.
Sexual selection maintains whole‐body chiral dimorphism in snails
Authors: SCHILTHUIZEN M. , CRAZE P. G. , CABANBAN A. S. , DAVISON A. , STONE J. , GITTENBERGER E. , SCOTT B. J.
Published: June 2007

Although the vast majority of higher animals are fixed for one chiral morph or another, the cause for this directionality is known in only a few cases. In snails, for example, rare individuals of the opposite coil are unable to mate with individuals of normal coil, so directionality is maintained by frequency‐dependent selection. The snail subgenus Amphidromus presents an unexplained exception, because dextral (D) and sinistral (S) individuals occur sympatrically in roughly equal proportions (so‐called ‘antisymmetry’) in most species. Here we show that in Amphidromus there is sexual selection for dimorphism, rather than selection for monomorphism. We found that matings between D and S individuals occur more frequently than expected by chance. Anatomical investigations showed that the chirality of the spermatophore and the female reproductive tract probably allow a greater fecundity in such inter‐chiral matings. Computer simulation confirms that under these circumstances, sustained dimorphism is the expected outcome.
The spread of apomixis and its effect on resident genetic variation
Authors: ADOLFSSON S. , BENGTSSON B. O.
Published: June 2007

In a simulation model we investigated how much of the initial genetic variation that is retained in a population after a dominant mutation has brought apomixis to fixation in it. A marker allele associated with the apomixis mutation is generally retained after the fixation of apomixis, particularly if the two alleles are closely linked. The spread of asexuality, however, normally leads to almost no loss of genetic variation, neither with respect to cytotypes nor with respect to genotypes. This holds for large populations and apomixis mutants with strong pollen production. In smaller populations, and with apomicts with reduced pollen production, the outcome is more variable, ranging from no genetic variation retained to only weakly reduced variability compared with the initial state. These results help explain the high genetic variability in many apomicts. They also imply that natural selection will have many genotypes to act on even after the spread of apomixis.
How to separate genetic and environmental causes of similarity between relatives
Authors: KRUUK L. E. B. , HADFIELD J. D.
Published: June 2007

Related individuals often have similar phenotypes, but this similarity may be due to the effects of shared environments as much as to the effects of shared genes. We consider here alternative approaches to separating the relative contributions of these two sources to phenotypic covariances, comparing experimental approaches such as cross‐fostering, traditional statistical techniques and more complex statistical models, specifically the ‘animal model’. Using both simulation studies and empirical data from wild populations, we demonstrate the ability of the animal model to reduce bias due to shared environment effects such as maternal or brood effects, especially where pedigrees contain multiple generations and immigration rates are low. However, where common environment effects are strong, a combination of both cross‐fostering and an animal model provides the best way to avoid bias. We illustrate ways of partitioning phenotypic variance into components of additive genetic, maternal genetic, maternal environment, common environment, permanent environment and temporal effects, but also show how substantial confounding between these different effects may occur. Whilst the flexibility of the mixed model approach is extremely useful for incorporating the spatial, temporal and social heterogeneity typical of natural populations, the advantages will inevitably be restricted by the quality of pedigree information and care needs to be taken in specifying models that are appropriate to the data.
Variable visual habitats may influence the spread of colourful plumage across an avian hybrid zone
Authors: UY J. A. C. , STEIN A. C.
Published: June 2007

Several studies have shown that hybridization can be a creative process by acting as a conduit for the spread of adaptive traits between species, but few provide the mechanism that favours this spread. In the hybrid zone between the golden‐ (Manacus vitellinus) and white‐collared (Manacus candei) manakins, sexual selection drives the introgression of golden/yellow plumage into the white species; however, the mechanism for the yellow male's mating advantage and the reasons why yellow plumage has not swept further into the white species remain mostly speculative. We quantified the colour properties of male plumage, the background and the ambient light at the hybrid zone, and allopatric golden and white populations. As measured by the perceived difference in colour between plumage and background, we found that yellow plumage appears more conspicuous than white plumage in the hybrid zone and allopatric golden‐collar habitats, whereas white plumage appears more conspicuous than yellow plumage in the allopatric white‐collared habitat. These results suggest a mechanism for the unidirectional spread of yellow plumage across the hybrid zone but slowed movement beyond it.
Histopathological Study of the Alternaria solani Infection Process in Potato Cultivars with Different Levels of Early Blight Resistance
Authors: Dita M. A. , Brommonschenkel S. H. , Matsuoka K. , Mizubuti E. S. G.
Published: June 2007

Histopathological analyses of the infection process of Alternaria solani were accomplished in three potato cultivars with different levels of early blight resistance. Leaflets of Aracy (resistant), Delta (moderately resistant) and Bintje (susceptible) cultivars were inoculated at the beginning of the flowering stage. In order to study the effect of leaf age, leaf samples were collected separately, in the lower, middle and upper third of the plants. Conidia germination, appressoria formation, penetration and number of penetration sites exhibiting hypersensitive response (HR) were qualitatively and quantitatively assessed at 6, 12, 24, 48 and 72 h after inoculation. Penetration occurred most frequently through the junctions of the epidermal cells. Penetrations through stomata were rarely observed. There was no association between the events and the resistance levels, except for the number of penetration sites showing HR that was highest in Aracy, intermediate in Delta and lowest in Bintje. Similarly, the number of sites with HR was the only event associated with the leaf age. Regardless of cultivar resistance levels, the number of the penetration sites with HR was higher in leaves in the upper part of the plant. These results suggest that HR may be one of the mechanisms associated with age‐related and genetic resistance to early blight in potato.
Isolation of Pseudomonas spp. from Diseased Capsicum chinense (Habanero Pepper) Plants in Yucatan, Mexico
Authors: Moguel‐Salazar F. , Quijano‐Ramayo A. , Keb‐Llanes M. , Moreno‐Valenzuela O. , Islas‐Flores I.
Published: June 2007

Capsicum chinense (habanero pepper) grown in Yucatan, Mexico, is frequently diseased by plant bacterial pathogens, but the bacterial agents remain unidentified. Bacteria associated with diseased C. chinense were isolated and characterized. Two isolates, ChA11 and ChA14, induced hypersensitive response in C. chinense plantlets and caused rot in C. chinense fruit and potato slices. Molecular identification showed both to be Pseudomonas spp. This is the first report identifying Pseudomonas spp. associated with C. chinense grown in Yucatan, and may represent a first step towards developing control measures against this insidious pathogen.
Biocontrol and Plant Pathogenic Fusarium oxysporum‐Induced Changes in Phenolic Compounds in Tomato Leaves and Roots
Authors: Panina Y. , Fravel D. R. , Baker C. J. , Shcherbakova L. A.
Published: June 2007

The biocontrol fungus Fusarium oxysporum strain CS‐20 was previously shown to reduce the incidence of Fusarium wilt of tomato through an uncharacterized host‐mediated response. As phenolic compounds are involved in the defence response of tomato to pathogens and other stressors, this work was undertaken to determine whether biocontrol strains induced changes in phenolic compounds in leaves and roots of tomato seedlings in the presence and absence of pathogenic F. oxysporum f. sp. lycopersici. Roots of intact tomato seedlings were placed in water or aqueous fungal spore suspensions. Two biocontrol F. oxysporum strains [CS‐20 (host‐mediated mechanism) and 85SK‐1 (control mechanism unknown)] and two plant pathogenic strains of F. oxysporum f. sp. lycopersici Race 1 were used. After 24 or 72 h exposure, phenolic compounds were extracted from leaves and roots before identification by HPLC. There were significant qualitative and quantitative differences between the two sampling times. Compared with the control treatment, strain CS‐20 significantly altered (usually increasing) the ferulic, caffeic and vanillic acid contents, and concentrations once unidentified phenolic compounds recovered from leaves and roots. In another experiment, tomato seedlings growing in sterile sand were drenched with spores of strain CS‐20 the day before treating them with varying concentrations of spores of the pathogen for 24 or 72 h. The amount of pathogen present did not significantly affect the plant phenolic response to the presence of strain CS‐20. This work demonstrates that tomato responds within 24 h to the presence of the biocontrol strain CS‐20 by alterations in secondary metabolism that are typical of resistance responses in tomato.