bluuebunny/crossref_metadata_2025 huggingface dataset:
A polymorphism within the equine CRISP3 gene is associated with stallion fertility in Hanoverian warmblood horses
Authors: Hamann H. , Jude R. , Sieme H. , Mertens U. , Töpfer‐Petersen E. , Distl O. , Leeb T.
Published: April 2007

Fertility of stallions is of high economic importance, especially for large breeding organisations and studs. Breeding schemes with respect to fertility traits and selection of stallions at an early stage may be improved by including molecular genetic markers associated with traits. The genes coding for equine cysteine‐rich secretory proteins (CRISPs) are promising candidate genes because previous studies have shown that CRISPs play a role in the fertilising ability of male animals. We have previously characterised the three equine CRISP genes and identified a non‐synonymous polymorphism in the CRISP1 gene. In this study, we report one non‐synonymous polymorphism in the CRISP2 gene and four non‐synonymous polymorphisms in the CRISP3 gene. All six CRISP polymorphisms were genotyped in 107 Hanoverian breeding stallions. Insemination records of stallions were used to analyse the association between CRISP polymorphisms and fertility traits. Three statistical models were used to evaluate the influence of single mutations, genotypes and haplotypes of the polymorphisms. The CRISP3 AJ459965:c.+622G>A SNP leading to the amino acid substitution E208K was significantly associated with the fertility of stallions. Stallions heterozygous for the CRISP3 c.+622G>A SNP had lower fertility than homozygous stallions (P = 0.0234). The pregnancy rate per cycle in these stallions was estimated to be ∼7% lower than in stallions homozygous at this position.
A QTL study of growth and body shape in the inter‐species hybrid of Père David's deer (Elaphurus davidianus) and red deer (Cervus elaphus)
Authors: Maqbool N. J. , Tate M. L. , Dodds K. G. , Anderson R. M. , McEwan K. M. , Mathias H. C. , McEwan J. C. , Hall R. J.
Published: April 2007

An interspecies deer hybrid resource population developed from a cross of Père David's and red deer was used to detect QTL that account for species differences. A genome scan, coupled with composite interval mapping, was conducted to search for QTL controlling body measurements at pre‐pubescent age (6 months of age) and puberty (15 months of age) in this interspecies hybrid. Five linkage groups that harbour QTL affecting morphology were identified. A joint‐traits analysis was used to search for putative pleiotropic QTL on four of these linkage groups, and three were significantly associated with pleiotropic QTL for nose width and foot length (metacarpal and phalanges), which collectively accounted for 29–58% of the phenotypic difference between the two deer species. This study suggests that a few loci with large pleiotropic effects may be responsible for species‐specific differences in growth and structure‐related traits.
An advanced sheep (Ovis aries, 2n = 54) cytogenetic map and assignment of 88 new autosomal loci by fluorescence in situ hybridization and R‐banding
Authors: Di Meo G. P. , Perucatti A. , Floriot S. , Hayes H. , Schibler L. , Rullo R. , Incarnato D. , Ferretti L. , Cockett N. , Cribiu E. , Williams J. L. , Eggen A. , Iannuzzi L.
Published: April 2007

Presented herein is an updated sheep cytogenetic map that contains 452 loci (291 type I and 161 type II) assigned to specific chromosome bands or regions on standard R‐banded ideograms. This map, which significantly extends our knowledge of the physical organization of the ovine genome, includes new assignments for 88 autosomal loci, including 74 type I loci (known genes) and 14 type II loci (SSRs/microsatellite marker/STSs), by FISH‐mapping and R‐banding. Comparison of the ovine map to the cattle and goat cytogenetic maps showed that common loci were located within homologous chromosomes and chromosome bands, confirming the high level of conservation of autosomes among ruminant species. Eleven loci that were FISH‐mapped in sheep (B3GAT2, ASCC3, RARSL, BRD2, POLR1C, PPP2R5D, TNRC5, BAT2, BAT4, CDC5L and OLA‐DRA) are unassigned in cattle and goat. Eleven other loci (D3S32, D1S86, BMS2621, SFXN5, D5S3, D5S68, CSKB1, D7S49, D9S15, D9S55 and D29S35) were assigned to specific ovine chromosome (OAR) bands but have only been assigned to chromosomes in cattle and goat.
Low‐dose lenograstim is as effective as standard dose in shortening neutrophil engraftment time following myeloablative chemotherapy and peripheral blood progenitor cell rescue
Authors: Nolan L. , Lorigan P. , Chilton S. , Newman J. , Else R. , Smith P. , Linch D. , Sweetenham J. W. , Johnson P. W.
Published: April 2007

Granulocyte colony‐stimulating factor (G‐CSF) is widely used following myeloablative chemotherapy (high‐dose therapy; HDT) and peripheral blood progenitor cell rescue (PBPCR) to reduce neutrophil engraftment time. The dose and duration required to gain maximum clinical and economic benefit has not been fully investigated. This double blind placebo‐controlled randomised trial was performed to determine whether short course low‐dose or standard‐dose Lenograstim (L) would influence recovery of haematopoiesis following HDT and PBPCR. Sixty‐one patients were randomised between May 1999 and November 2004, to receive standard‐dose lenograstim (263 μg/d), low‐dose lenograstim (105 μg/d) or placebo injections. These commenced on day +5 following PBPCR and continued until neutrophil engraftment [absolute neutrophil count (ANC)] ≥ 0·5 × 109/l. Patients received standard supportive care until haemopoietic recovery. Both standard‐ and low‐dose lenograstim resulted in a significantly shorter median time to neutrophil recovery (ANC ≥ 0·1 × 109/l:10·0 vs. 11·0 d, P = 0·025; ANC ≥ 0·5 × 109/l:11·0 vs. 14·0 d, P = 0·0002) compared with placebo. There was no significant difference in blood product support, antibiotic usage, documented infection, overall survival or relapse‐free survival between the groups. Short course low‐dose lenograstim is as effective as standard‐dose in reducing neutrophil engraftment time following HDT and PBPCR.
Hybrid genetic algorithms in view of the evolution theories with application for the electrical sounding method
Authors: Başokur Ahmet T. , Akça Irfan , Siyam Nedal W.A.
Published: April 2007

The classical genetic algorithm is a stochastic process which operates by natural selection. Although the algorithm may localize a point around the global minimum of the misfit function, it is not efficient at finding the precise solution. This paper suggests some hybrid genetic algorithms, derived from evolution theories, to overcome this problem. Firstly, sexual selection has been incorporated in the classical genetic algorithm to obtain a full representation of the Darwinist evolution concept. The simulation of sexual selection is performed by assigning a higher probability of surviving to some parameters that satisfy some algebraic relationships. This method is called the ‘marked constraints’ algorithm since it permits us to insert geological and geophysical constraints into the problem. The algorithm implementation is realized by progressively shrinking the parameter search space through successive generations. In this way, the genetic algorithm gains some degree of determinism. Secondly, since the evolution theory of Lamarck postulates that the acquired traits are passed on to the next generation, a hybrid use of the damped least‐squares method and the genetic algorithm is called Lamarckian inversion. Lamarckian inversion involves some improvement procedures that simulate the reduction of the misfit with the help of a derivative‐based method between two generations. Finally, although there is no correspondence in nature, Lamarckian and Darwinist evolution concepts are combined to strengthen the deterministic part of the solution algorithm. This is called the Lamarckian‐marked‐constraint algorithm. The merits and behaviours of the suggested algorithms are discussed using two examples. The first is a hypothetical example affected by a multiminima problem. The second examines the equivalence problem using vertical electrical sounding data.
Fluid‐dependent shear‐wave splitting in a poroelastic medium with conjugate fracture sets
Authors: Galvin Robert J. , Gurevich Boris , Sayers Colin M.
Published: April 2007

The dependence of shear‐wave splitting in fractured reservoirs on the properties of the filling fluid may provide a useful attribute for identifying reservoir fluids. If the direction of wave propagation is not perpendicular or parallel to the plane of fracturing, the wave polarized in the plane perpendicular to the fractures is a quasi‐shear mode, and therefore the shear‐wave splitting will be sensitive to the fluid bulk modulus. The magnitude of this sensitivity depends upon the extent to which fluid pressure can equilibrate between pores and fractures during the period of the deformation. In this paper, we use the anisotropic Gassmann equations and existing formulations for the excess compliance due to fracturing to estimate the splitting of vertically propagating shear waves as a function of the fluid modulus for a porous medium with a single set of dipping fractures and with two conjugate fracture sets, dipping with opposite dips to the vertical. This is achieved using two alternative approaches. In the first approach, it is assumed that the deformation taking place is quasi‐static: that is, the frequency of the elastic disturbance is low enough to allow enough time for fluid to flow between both the fractures and the pore space throughout the medium. In the second approach, we assume that the frequency is low enough to allow fluid flow between a fracture set and the surrounding pore space, but high enough so that there is not enough time during the period of the elastic disturbance for fluid flow between different fracture sets to occur. It is found that the second approach yields a much stronger dependence of shear‐wave splitting on the fluid modulus than the first approach. This is a consequence of the fact that at higher wave frequencies there is not enough time for fluid pressure to equilibrate and therefore the elastic properties of the fluid have a greater effect on the magnitude of the shear‐wave splitting.
Elastic‐impedance analysis constrained by rock‐physics bounds†
Authors: Tsuneyama Futoshi , Mavko Gary
Published: April 2007

By applying seismic inversion, we can derive rock impedance from seismic data. Since it is an interval property, impedance is valuable for reservoir characterization. Furthermore, the decomposition of the impedance into two fundamental properties, i.e. velocity and density, provides a link to the currently available rock‐physics applications to derive quantitative reservoir properties. However, the decomposition is a challenging task due to the strong influence of noise, especially for seismic data with a maximum offset angle of less than 30°. We present a method of impedance decomposition using three elastic impedance data derived from the seismic inversion of angle stacks, where the far‐stack angle is 23.5°. We discuss the effect of noise on the analysis as being the most significant cause of making the decomposition difficult. As the result, the offset‐consistent component of noise mostly affects the determination of density but not the velocities (P‐ and S‐wave), whereas the effect of the random component of noise occurs equally in the determination of the velocities and density. The effect is controlled by the noise enhancement factor 1/A, which is determined by a combination of stack angles. Based on the results of the analysis, we show an innovative method of decomposition incorporating rock‐physics bounds as constraints for the analysis. The method is applied to an actual data set from an offshore oilfield; we demonstrate the result of analysis for sandbody detection.
Overburden complexity and repeatability of seismic data: Impacts of positioning errors at the Oseberg field, North Sea
Authors: Misaghi Ali , Landrø Martin , Petersen Steen A.
Published: April 2007

Repeatability of seismic data plays a crucial role in time‐lapse seismic analysis. There are several factors that can decrease the repeatability, such as positioning errors, varying tide, source variations, velocity changes in the water layer (marine data) and undesired effects of various processing steps. In this work, the complexity of overburden structure, as an inherent parameter that can affect the repeatability, is studied. A multi‐azimuth three‐dimensional vertical‐seismic‐profiling data set with 10 000 shots is used to study the relationship between overburden structure and repeatability of seismic data. In most repeatability studies, two data sets are compared, but here a single data set has been used because a significant proportion of the 10 000 shots are so close to each other that a repeatability versus positioning error is possible. We find that the repeatability decreases by a factor of approximately 2 under an overburden lens. Furthermore, we find that the X‐ and Y‐components have approximately the same sensitivity to positioning errors as the Z‐component (for the same events) in this three‐dimensional vertical‐seismic‐profiling experiment. This indicates that in an area with complex overburden, positioning errors between monitor and base seismic surveys are significantly more critical than outside such an area. This study is based on a three‐dimensional three‐component vertical‐seismic‐profiling data set from a North Sea reservoir and care should be taken when extrapolating these observations into a general four‐dimensional framework.
Elastic behaviour of North Sea chalk: A well‐log study
Authors: Gommesen L. , Fabricius I.L. , Mukerji T. , Mavko G. , Pedersen J.M.
Published: April 2007

We present two different elastic models for, respectively, cemented and uncemented North Sea chalk well‐log data. We find that low Biot coefficients correlate with anomalously low cementation factors from resistivity measurements at low porosity and we interpret this as an indication of cementation. In contrast, higher Biot coefficients and correspondingly higher cementation factors characterize uncemented chalk for the same (low) porosity. Accordingly, the Poisson's ratio–porosity relationship for cemented chalk is different from that of uncemented chalk.

We have tested the application of the self‐consistent approximation, which here represents the unrelaxed scenario where the pore spaces of the rock are assumed to be isolated, and the Gassmann theory, which assumes that pore spaces are connected, as tools for predicting the effect of hydrocarbons from the elastic properties of brine‐saturated North Sea reservoir chalk. In the acoustic impedance–Poisson's ratio plane, we forecast variations in porosity and hydrocarbon saturation from their influence on the elastic behaviour of the chalk. The Gassmann model and the self‐consistent approximation give roughly similar predictions of the effect of fluid on acoustic impedance and Poisson's ratio, but we find that the high‐frequency self‐consistent approach gives a somewhat smaller predicted fluid‐saturation effect on Poisson's ratio than the low‐frequency Gassmann model. The Gassmann prediction for the near and potentially invaded zone corresponds more closely to logging data than the Gassmann prediction for the far, virgin zone. We thus conclude that the Gassmann approach predicts hydrocarbons accurately in chalk in the sonic‐frequency domain, but the fluid effects as recorded by the acoustic tool are significantly affected by invasion of mud filtrate.

The amplitude‐versus‐angle (AVA) response for the general North Sea sequence of shale overlying chalk is predicted as a function of porosity and pore‐fill. The AVA response of both cemented and uncemented chalk generally shows a declining reflectivity coefficient versus offset and a decreasing normal‐incidence reflectivity with increasing porosity. However, for the uncemented model, a phase reversal will appear at a relatively lower porosity compared to the cemented model.
On the retrieval of moment tensors from borehole data
Authors: Vavryčuk Václav
Published: April 2007

The complete moment tensors of seismic sources in homogeneous or vertically inhomogeneous isotropic structures cannot be retrieved using receivers deployed in one vertical borehole. The complete moment tensors can be retrieved from amplitudes of P‐waves, provided that receivers are deployed in at least three boreholes. Using amplitudes of P‐ and S‐waves, two boreholes are, in principle, sufficient. Similar rules also apply to transversely isotropic media with a vertical axis of symmetry.

In the case of limited observations, the inversion can be stabilized by imposing the zero‐trace constraint on the moment tensors. However, this constraint is valid only if applied to observations of shear faulting on planar faults in isotropic media, which produces double‐couple mechanisms. For shear faulting on non‐planar faults, for tensile faulting, and for shear faulting in anisotropic media, the zero‐trace constraint is no longer valid and can distort the retrieved moment tensor and bias the fault‐plane solution.

Numerical modelling simulating the inversion of the double‐couple mechanism from real data reveals that the errors in the double‐couple and non‐double‐couple percentages of the moment tensors rapidly decrease with increase in the number of boreholes used. For noisy P‐ and S‐wave amplitudes with noise of 15% of the top amplitude at each channel and for a velocity model biased by 10%, the errors in the double‐couple percentage attain 25, 13 and 6% when inverting for the double‐couple mechanism from one, two and three boreholes.
Triacylated lipoproteins derived from Mycoplasma pneumoniae activate nuclear factor‐κB through toll‐like receptors 1 and 2
Authors: Shimizu Takashi , Kida Yutaka , Kuwano Koichi
Published: April 2007

Summary Pathogenesis of Mycoplasma pneumoniae infection is considered to be in part attributed to excessive immune responses. Recently, a mycoplasma lipoprotein has been shown to induce nuclear factor κB (NF‐κB) activation through toll‐like receptor 1 (TLR1), TLR2 and TLR6. In this study, we examined the ability of lipoproteins from M. pneumoniae to activate NF‐κB through TLR1‐ and TLR2‐dependent, but TLR6‐independent, pathways, and the active components responsible for the NF‐κB activation through the TLR6‐independent pathway were identified. The active lipoproteins were found to be MPN611 and MPN162 of M. pneumoniae (designated N‐ALP1 and N‐ALP2, respectively). Purified N‐ALP1 and N‐ALP2 from M. pneumoniae and triacylated partial synthetic lipopeptides of N‐ALP1 and N‐ALP2 augmented the levels of NF‐κB induction through TLR1‐ and TLR2‐dependent pathways, whereas diacylated partial synthetic lipopeptides of N‐ALP1 and N‐ALP2 activated NF‐κB through TLR1‐, TLR2‐ and TLR6‐dependent pathways. These data suggest that N‐ALP1 and N‐ALP2 would be triacylated lipoproteins. The activity of N‐ALP1 and N‐ALP2 was decreased with a pretreatment of lipoprotein lipase, and partially decreased by protease treatment, indicating that the lipid moiety of N‐ALP1 and N‐ALP2 is critical for the NF‐κB activation. Thus, triacylated lipoproteins derived from M. pneumoniae might activate NF‐κB through TLR1 and TLR2, but not TLR6.
Disruption of Rxra gene in thymocytes and T lymphocytes modestly alters lymphocyte frequencies, proliferation, survival and T helper type 1/type 2 balance
Authors: Stephensen Charles B. , Borowsky Alexander D. , Lloyd Kevin C. Kent
Published: April 2007

Retinoid X receptor (RXR) agonists, including the vitamin A metabolite 9‐cis retinoic acid, decrease T‐lymphocyte apoptosis and promote T helper type 2 (Th2) development ex vivo. To examine the in vivo role of RXR‐α in T‐lymphocyte development and function, we disrupted the Rxra gene in thymocytes and T lymphocytes using cyclization recombinase (Cre)‐loxP‐mediated excision of Rxra exon 4. Expression of Cre was targeted to these cells using the Lck promoter. Successful disruption of exon 4 was seen in thymus and T lymphocytes. Mice were healthy and the thymus, spleen and lymph nodes appeared normal. However, knockout mice had a lower percentage of double‐positive (CD4+ CD8+) and a higher percentage of double‐negative thymocytes than wild‐type mice. The percentage of splenic B lymphocytes was lower in unimmunized and ovalbumin‐immunized knockout mice and the percentage of T lymphocytes was lower in immunized knockout mice. Ex vivo proliferation was decreased and apoptosis was increased in T lymphocytes from knockout mice. Memory CD4+ T lymphocytes from knockout mice produced more interferon‐γ and interleukin‐2 (IL‐2) and less IL‐5 and IL‐10 than memory cells from wild‐type mice, indicating a Th1 bias in vivo. However, Rxra disruption did not similarly bias ex vivo differentiation of naive CD4+ T lymphocytes, nor did Rxra disruption alter the serum immunoglobulin G1/immunoglobulin G2a response to immunization. In summary, disruption of Rxra altered the percentages of T and B lymphocytes, produced a Th1 bias in vivo, and altered T‐lymphocyte proliferation and apoptosis ex vivo. These differences were modest in magnitude and their impact on disease resistance is yet to be examined.
A method for assessment of quality of life in relation to prosthodontics. Partial edentulism and removable partial dentures
Authors: ÖZHAYAT E. B. , STOLTZE K. , ELVERDAM B. , ÖWALL B.
Published: April 2007

summary The aim of this study was to evaluate the possible use in prosthodontics of a method for an interview technique allowing maximal individuality within the cultural boundaries. The impact of partial edentulism and removable partial denture (RPD) wearing on quality of life was chosen as the target question. The interview included patient generated selection of five quality of life cues. The current status/intensity of each cue was measured by use of a Visual Analogue Scale (VAS), the relative weight/importance between the cues by a direct‐weighting (DW) instrument, and a summarized quality of life score was calculated. One hundred and one participants with partial edentulism with or without RPDs were included in the study. No correlation was found between the VAS‐ and DW‐scores, indicating that different aspects are measured with these two instruments. Sixty to seventy per cent of the participants answered positively to questions about the test method, including self‐knowledge, consciousness and identification of needs and wishes. The ‘Schedule for the Evaluation of Individual Quality of Life – Direct Weighting’ turned out to be a useful instrument for assessing patients’ priorities, and fulfils in many ways the demands for individualized problem identification, decision‐making and treatment planning. The results of the comparison of RPD wearers and non‐RPD wearers showed that aesthetics is a major factor and that the overall quality of life between the experienced RPD wearers and non‐RPD wearers in this study did not differ significantly.
Genetic diversity, but not hatching success, is jointly affected by postglacial colonization and isolation in the threatened frog, Rana latastei
Authors: FICETOLA GENTILE FRANCESCO , GARNER TRENTON W. J. , DE BERNARDI FIORENZA
Published: April 2007

Both postglacial colonization and habitat fragmentation can reduce the genetic diversity of populations, which in turn can affect fitness. However, since these processes occur at different spatial and temporal scales, the consequences of either process may differ. To disentangle the relative role of isolation and postglacial colonization in determining genetic diversity and fitness, we studied microsatellite diversity of 295 individuals from 10 populations and measured the hatch rate of 218 clutches from eight populations of a threatened frog, R. latastei. The populations that were affected by fragmentation to a greater extent suffered higher embryo mortality and reduced hatch rate, while no effects of distance from glacial refugium on hatch rate were detected. Altogether, distance from glacial refugium and isolation explained > 90% of variation in genetic diversity. We found that the genetic diversity was lowest in populations both isolated and far from the glacial refugium, and that distance from refugium seems to have the primary role in determining genetic diversity. The relationship between genetic diversity and hatch rate was not significant. However, the proportion of genetic diversity lost through recent isolation had a significant, negative effect on fitness. It is possible that selection at least partially purged the negative effects of the ancestral loss of genetic diversity.
Age‐dependent genetic effects on a secondary sexual trait in male Alpine ibex,Capra ibex
Authors: VON HARDENBERG ACHAZ , BASSANO BRUNO , FESTA‐BIANCHET MARCO , LUIKART GORDON , LANFRANCHI PAOLO , COLTMAN DAVID
Published: April 2007

Secondary sexual traits, such as horns in ungulates, may be good indicators of genetic quality because they are costly to develop. Genetic effects on such traits may be revealed by examining correlations between multilocus heterozygosity (MLH) and trait value. Correlations between MLH and fitness traits, termed heterozygosity–fitness correlations (HFC), may reflect inbreeding depression or associative overdominance of neutral microsatellite loci with loci directly affecting fitness traits. We investigated HFCs for horn growth, body mass and faecal counts of nematode eggs in wild Alpine ibex (Capra ibex). We also tested if individual inbreeding coefficients (f′) estimated from microsatellite data were more strongly correlated with fitness traits than MLH. MLH was more strongly associated with trait variation thanf′. We found HFC for horn growth but not for body mass or faecal counts of nematode eggs. The effect of MLH on horn growth was age‐specific. The slope of the correlation between MLH and yearly horn growth changed from negative to positive as males aged, in accordance with the mutation accumulation theory of the evolution of senescence. Our results suggest that the horns of ibex males are an honest signal of genetic quality.
Intramuscular hepatitis B immunoglobulin (HBIG) and nucleosides for prevention of recurrent hepatitis B following liver transplantation: comparison with other HBIG regimens
Authors: Anderson Robert D , Chinnakotla Srinath , Guo Linsheng , Perrillo Robert P , Klintmalm Göran B , Davis Gary L
Published: April 2007

Abstract:  High titer hepatitis B immunoglobulin (HBIG) has significantly reduced the recurrence of hepatitis B virus (HBV) infection after liver transplantation. We compared our experience with intramuscular (IM) HBIG prophylaxis to our earlier outcomes with intravenous (IV) HBIG and other regimens.

Methods:  One hundred and twenty‐three patients with acute or chronic hepatitis B underwent liver transplant at the Baylor Regional Transplant Center between July 1985 and July of 2005. Of these, 63 (43%) received long‐term low‐dose IM (n = 17) or high‐dose IV (n = 46) HBIG. All patients in IM group also received a nucleoside before and after transplant. These patients were compared with those transplanted earlier who received either no prophylaxis (n = 16) or HBIG on day zero and one only (n = 44).

Results:  HBV recurrence was significantly lower in patients who received long‐term HBIG [9/38 (23.7%) for IV and 1/17 (5.9%) for IM] compared with patients who received no treatment (8/11; 72.7%) or only two doses of HBIG (32/40; 80.0%). Two‐yr actuarial survivals were 89%, 88%, 54%, and 64%, respectively. Patients on long‐term HBIG by either parenteral route survived as well as patients transplanted for other indications. Post‐transplant recurrence of hepatitis B in the long‐term HBIG groups was usually controlled by intensifying antiviral therapy.

Conclusion:  Long‐term low‐dose IM and high‐dose IV HBIG are equally efficacious with similar survival and early hepatitis recurrence rates. Graft loss is usually avoidable when recurrence is discovered early and aggressively treated. The IM route is preferable to IV administration due to its ease of administration and lower cost.
Post‐transplant ischemic injury is associated with up‐regulated AlloMap gene expression
Authors: Yamani M.H. , Taylor D.O. , Haire C. , Smedira N. , Starling R.C.
Published: April 2007

Abstract:  Background:  The AlloMap gene expression test is used for the non‐invasive detection of rejection. However, the impact of early post‐transplant ischemic injury on subsequent AlloMap gene expression analysis has not been evaluated before.

Methods:  Sixty seven heart transplant recipients, mean age 53 years, were evaluated at a mean 34 months post‐transplant. AlloMap score was determined on the same day of heart biopsies. Nineteen patients had evidence of early post‐transplant ischemic injury (Injury group). These were compared with the remaining 48 patients, Control group.

Results:  Using multiple regression model with a backward selection method, post‐transplant ischemic injury was found to be associated with significant increased AlloMap score compared with controls (31.5 ± 4.6 vs. 26 ± 6.2, p < 0.001). The Injury group had increased transplant vasculopathy (KM 5‐year freedom from vasculopathy: 34% vs. 52%, p = 0.015), than Controls.

Conclusions:  Post‐transplant ischemic injury is associated with up‐regulated AlloMap gene expression, and hence, may provide another explanation for a high score in the absence of rejection.
Clinical outcomes of renal transplant recipients treated with enteric‐coated mycophenolic acid vs. mycophenolate mofetil as a switch agent using a primary steroid‐free rapamune and microemulsion cyclosporine protocol
Authors: Pelletier R.P. , Soule J. , Henry M.L. , Rajab A. , Ferguson R.M.
Published: April 2007

Abstract:  Since 2002 our transplant program has utilized a steroid free, cyclosporine (CSA)‐ and rapamycin (RAPA)‐based maintenance immunosuppression regimen. In cases where it has been desirable to avoid the potential nephrotoxicity with this regimen we have used mycophenolic acid (MPA) as our “switch” drug of choice. Both mycophenolate mofetil (MMF) (Roche Inc., Nutley, NJ, USA) and enteric‐coated MPA (ECM) (Novartis, East Hanover, NJ, USA) have been used. In this study, we retrospectively compared the tolerability of the two formulations of MPA. Thus we compared 103 recipients switched to RAPA/MMF (RMM group) to 114 switched to RAPA/ECM (REC group). There was a significantly higher incidence of patients requiring dose changes and drug discontinuation in the RMM group, as well as an increased frequency of dose changes. There were significantly more acute rejection episodes and kidney losses in the dose adjustment vs. no dose adjustment patients. However, when comparing the incidence of acute rejection and kidney loss between the RMM and REC groups, there was no significant difference. We conclude that in this cohort of recipients, the ECM formulation of MPA was better tolerated than the MMF formulation, resulting in fewer patients requiring dose adjustments or drug discontinuation.
Neurologic complications in adult living donor liver transplant recipients
Authors: Kim Bum‐Soo , Lee Sung‐Gyu , Hwang Shin , Park Kwang‐Min , Kim Ki‐Hun , Ahn Chul‐Soo , Moon Deok‐Bog , Ha Tae‐Yong , Song Gi‐Won , Kim Dong‐Sik , Moon Ki‐Myung , Jung Dong‐Hwan
Published: April 2007

Abstract:  Background:  Neurologic complications (NC) after liver transplantation are not uncommon, with serious complications such as central pontine myelinolysis (CPM), often causing disability.

Objective:  We investigated the incidence and features of NC following liver transplantation in adult recipients.

Patients and methods:  We retrospectively reviewed the medical records of 319 adult patients who underwent liver transplantation between January 2004 and May 2005 at the Asan Medical Center.

Results:  Neurologic complications developed in 49 of 319 patients (15.4%). Although most of these complications were minor, including tremor and foot drop, three patients developed CPM, and one each developed posterior leukoencephalopathy, cerebral hemorrhage, and cerebral infarction. One‐yr survival rates were 95.9% in patients without NC and 83.7% in patients with NC (p = 0.004). Hospital stay was prolonged in patients with NC. Graft‐to‐recipient body weight ratio (GRWR) did not affect occurrence of NC.

Conclusions:  Neurologic complications were not uncommon in liver transplant recipients. These complications contributed to prolongation of hospital stay, increased in‐hospital mortality, and decreased graft and patient survival. Every effort should be made to prevent NC, as well as to detect and treat them as soon as possible.
Clinical trial on the cost‐effectiveness of T‐tube use in an established deceased donor liver transplantation program
Authors: Amador A. , Charco R. , Martí J. , Navasa M. , Rimola A. , Calatayud D. , Rodriguez‐Laiz G. , Ferrer J. , Romero J. , Ginesta C. , Fondevila C. , Fuster J. , García‐Valdecasas J.C.
Published: April 2007

Abstract:  The aim of our study was to assess the advantages and disadvantages of T‐tube use in liver transplantation, with also paying attention to the economic costs derived from its use. Patients were prospectively randomized to T tube or no T tube. One hundred and seven patients, 53 with T tube and 54 without T tube, were analyzed. Minimum follow‐up was three months. Nine patients (8.4%) had bile leak: six in the T‐tube group (11.3%) and three in the group without T tube (5.5%), p = ns. Four patients (3.5%) had anastomotic biliary stenosis: one in the T‐tube group (1.8%) and three in the group without T tube, p = ns. Twenty of the 53 patients (37.7%) with T tube had T‐tube‐related complication. The number of diagnostic and therapeutic resources were higher in the T‐tube group compared with non‐T tube (81 and 17 vs. 18 and 10, respectively, p <0.05). The costs of therapeutic procedures required for the treatment of complications were 28 232 € in the T‐tube group vs. 16 088 € in the no T‐tube group, p <0.05. In conclusion, the systematic use of the T tube in biliary reconstruction in liver transplantation cannot be justified.
Health preparations and travel‐related morbidity of kidney transplant recipients traveling to developing countries
Authors: Roukens A.H.E. , Van Dissel J.T. , De Fijter J.W. , Visser L.G.
Published: April 2007

Abstract:  A cross‐sectional, descriptive study was conducted among Dutch kidney transplant recipients to investigate travel health knowledge, attitudes and practices while staying abroad. A total of 290 individuals visiting the nephrology outpatient clinic completed the questionnaires. Thirty four percent of the responders had traveled outside Western Europe (WE) and Northern America (NA); 22% of these travelers did not seek pre‐travel health advice. Transplant physicians were most frequently consulted for pre‐travel advice (53%). Of the responders traveling outside WE and NA 29% were ill during their most recent journey. Diabetic transplant recipients were at the highest risk. Four of seventeen ill recipients (24%) were hospitalized, reflecting the high morbidity of travel‐related disease in this patient group. Our data show that there is need for improvement of pre‐travel healthcare, and suggest an important role for transplant physicians in providing adequate counseling.
14th International HLA and Immunogenetics Workshop: Report on understanding antibodies in transplantation
Authors: Zachary A. A. , Montgomery R. A. , Jordan S. C. , Reinsmoen N. L. , Claas F. H. J. , Reed E. F.
Published: April 2007

A session of the 14 International Histocompatibility Workshop brought together experts representing the major clinical protocols, clinical research, and basic research dealing with overcoming the barrier of alloantibody in transplantation and in understanding the mechanisms by which those antibodies exert their effect on a transplanted organ. This report is an integration of the presentations of those scientists.
14th International HLA and Immunogenetics Workshop: Report on the structural basis of HLA compatibility
Authors: Duquesnoy R. J. , Claas F. H. J.
Published: April 2007

Under auspices of the 14th International Human Leukocyte Antigen (HLA) and Immunogenetics Workshop, multilaboratory collaborative studies were organized addressing the following projects: (1) identification of structurally defined class I and class II HLA epitopes by human monoclonal antibodies, (2) assessment of the relative immunogenicity of structurally defined donor HLA mismatches in kidney transplantation, and (3) evaluation of the usefulness of structurally based HLA matching in platelet transfusion support of alloimmunized thrombocytopenic patients. This progress report describes a preliminary HLAMatchmaker‐based data analysis in each project. The findings support the clinical usefulness of structural HLA matching.
Fourier transform infrared imaging as a method for detection of HLA class I expression in melanoma without the use of antibody
Authors: Chew S. F. , Wood B. R. , Kanaan C. , Browning J. , MacGregor D. , Davis I. D. , Cebon J. , Tait B. D. , McNaughton D.
Published: April 2007

Human leukocyte antigen (HLA) class I expression in melanoma is usually assessed using immunohistochemical staining. Here we report on the use of Fourier transform infrared (FTIR) hyperspectral imaging, a method widely used in two‐dimensional analysis of chemical components, to study HLA class I expression in tissue. Two‐dimensional cluster colour images derived from unsupervised hierarchical cluster analysis of FTIR hyperspectral data on melanoma sections were compared with consecutive sections that were immunohistochemically stained for class I expression. HLA‐class‐I‐positive and ‐negative areas were differentiated by FTIR cluster images in all eight melanoma sections investigated without the need for antibody attachment. FTIR imaging enables the distinction of HLA‐class‐I‐positive from class‐I‐negative areas in melanoma. This method is accurate, rapid and cost‐effective.
14th International HLA and Immunogenetics Workshop: Report on joint study on canine DLA diversity
Authors: Kennedy L. J.
Published: April 2007

The canine DLA diversity component of the 14th International HLA and Immunogenetics (IHI) Workshop had three main aims: i) to establish the range of DLA class II (DRBI, DQA1, DQB1) diversity and their distribution in dog breeds, ii) to identify DLA class II haplotypes by segregation in families and iii) to examine DLA class II associations with disease susceptibility. Over 1600 dogs from seven participating laboratories were typed for three DLA class II loci as part of the workshop. Standard sequence‐based typing methods were used, and all the data were of high quality.
Canine DLA diversity: 2. Family studies
Authors: Kennedy L. J. , Barnes A. , Short A. , Brown J. J. , Lester S. , Seddon J. , Happ G. M , Ollier W. E. R.
Published: April 2007

The canine Major Histocompatibility Complex is referred to as DLA (for dog leukocyte antigen). There are no published studies on DLA segregation in the dog, so this part of the DLA workshop aimed to collect DNA from multigeneration families of different breeds of dogs. Twenty‐two families of dogs were submitted to the workshop, comprising 313 individuals, of which 247 had one or both parents available.
Tools for analysing ambiguous HLA data
Authors: Nunes José M.
Published: April 2007

Analyses of large projects involving human leukocyte antigen data often face the difficulty of having data sets gathered using distinct techniques and resolution levels. Furthermore, it is not infrequent that missing and ambiguous data arise at one or several loci. This article describes a set of computer programs that can be used to work efficiently with these kinds of data. The tasks of concern include format conversions, data recoding and replacement, and Expectation–Maximization (gene–counting) based frequency estimation for sets with ambiguous cases either under the assumption of Hardy–Weinberg equilibrium frequencies or when some deviation exists (measured by a one degree of freedominbreeding coefficient). This set of utilities is built on the top of a data format formally defined. The formal definition of the format allows to express all kinds of observable ambiguities, to define a simpler form for writing and manipulating data set files and to make substantial modifications of the actual symbols chosen to describe the data.
Strategies for new donor typing based on donor HLA type or donor characteristics
Authors: Little A.‐M. , Jindra P. , Raffoux C.
Published: April 2007

Registries of volunteer unrelated haematopoietic stem cell donors must make decisions on the procedures used to human leukocyte antigen type new donors based on various factors including available finances and donor diversity. This manuscript describes a comparison of new donor typing strategies for three European registries which was presented for discussion at the 14th International Histocompatibility Workshop.
Quality control for registry HLA data
Authors: Tiercy J.‐M. , Fischer G. , Setterholm M.
Published: April 2007

In this panel discussion, the following issues were addressed: the evaluation of the quality of the volunteer donors human leukocyte antigen (HLA) assignments, the quality criteria that should be met by the laboratories, the source of errors, the measures that registries can take to assess the quality of HLA testing, and the updating of the initial result with emphasis on resolution of typing discrepancies. Several relevant factors were put forward: the need for the registries to define the HLA loci and the level of resolution requested, and the importance of the accreditation programs with adequate external proficiency testing. The feasibility of annual quality controls of a national registry addressing the limitations of HLA class I serology, and the rules set up by a large registry to incorporate new data on donors HLA types and to rapidly track typing discrepancies, were reported.
Improving communication among the HLA typing laboratories, transplant centers, and coordinating center
Authors: Gordon S. , Holdsworth R. , Müller C. , Tiedemann K.
Published: April 2007

Good communication between the bone marrow registries, the donor centres, tissue typing laboratories and clinical units is paramount to ensure timely identification, testing and selection of donors for unrelated bone marrow transplants. This panel session focussed on how to improve communication so that there was a clear understanding of prioritization of requests from clinicians, typing strategies in the laboratories and requests for donors to the registries. This paper outlined some of the strategies discussed in this session.
Clinical importance of HLA‐DPB1 in haematopoietic cell transplantation
Authors: Shaw B. E. , Gooley T. , Madrigal J. A. , Malkki M. , Marsh S. G. E. , Petersdorf E. W.
Published: April 2007

There is increasing evidence for a significant effect of human leukocyte antigen (HLA)‐DPB1 mismatching on complications following unrelated donor haematopoietic cell transplantation (HCT). In this analysis of 5930 patient/donor pairs, we found that a DPB1 mismatch predicted significantly for an increased risk of acute graft‐vs‐host disease [hazard ratio (HR): 1.33; P‐value = <0.0001], while protecting against disease relapse (HR: 0.82, P‐value = 0.01). These data support an immunogenic role for HLA‐DPB1 in HCT and the need for pretransplant tissue typing at this locus.
Hematopoietic stem cell transplantation: killer immunoglobulin‐like receptor component
Authors: Hsu K. C. , Pinto‐Agnello C. , Gooley T. , Malkki M. , Dupont B. , Petersdorf E. W.
Published: April 2007

Recognition of recipient human leukocyte antigen (HLA) class I ligand by donor natural killer cell killer immunoglobulin‐like receptors (KIR) has been proposed as the basis for donor allograft reactivity against malignancy leading to reduction in posttransplant relapse and higher survival for acute myelogenous leukemia. Analysis of KIR ligand effects in 1770 patients undergoing myeloablative T‐replete hematopoietic cell transplantation (HCT) from HLA‐matched or mismatched unrelated donors showed that lack of KIR ligand in patients for inhibitory KIR was associated with lower hazards of relapse in leukemia patients with in HLA‐mismatched transplants [hazard ratio (HR): 0.061; 95% confidence interval (CI): 0.43–0.85; P‐value = 0.004]. Absence of HLA‐C group 2 or HLA‐Bw4 KIR ligands were each associated with lower hazards of relapse (HR: 0.47; 95% CI: 0.28–0.79; P‐value = 0.004; HR: 0.56; 95% CI: 0.33–0.97; P‐value = 0.04, respectively). Based on these analyses, recipient homozygosity for HLA‐B or ‐C epitopes that define KIR ligands is likely to be a predictive factor for leukemia relapse following myeloablative HCT from unrelated donors. KIR genotyping for unrelated donors and recipients will clarify the role of these receptors in transplant outcome.
14th International HLA and Immunogenetics Workshop: Report from the Sequencing‐Based Typing Group
Authors: Tilanus M. , Sayer D. C
Published: April 2007

Sequencing‐Based Typing (SBT) provides the golden standard for the identification of polymorphism among the human leukocyte antigen (HLA) alleles. Several SBT approaches have been published. Updated protocols for HLA‐DRB and ‐DQB were presented and an approach for DQA, covering all exons, validated. The highest level of allele typing can be realized with strategies for resolving allele and genotype ambiguities. Bioinformatics provides the tools for exchange and sharing data with a community standard in XML format.
HLA‐DRB sequencing‐based typing: an improved protocol which shows complete DRB exon 2 sequences and includes exon 3 of HLA‐DRB4/5
Authors: Van Dijk A. , Melchers R. , Hilkes Y. , Rozemuller E. , Tilanus M.
Published: April 2007

Several human leukocyte antigen (HLA)‐DRB protocols for sequencing‐based typing have been described. In general, the DRB1 amplification is performed using group‐specific amplification primers (GSAPs) located in HVR I or intron 1. Only some protocols include amplification of DRB3, DRB4, and DRB5. However, prior knowledge obtained by alternative methods such as PCR‐SSP is preferred for some protocols and a large amount of DNA is often required for adequate typing of HLA‐DRB1. We describe a new protocol that uses GSAPs located in the introns, includes also sequencing of exon 3 to enable high resolution. This protocol allows DRB typing without prior knowledge of the HLA type.
HLA‐DQB1 sequencing‐based typing updated
Authors: Van Dijk A. , Melchers R. , Tilanus M. , Rozemuller E.
Published: April 2007

The use of direct sequencing as a typing strategy is well acknowledged. Direct sequencing identifies all sequence motifs including new polymorphisms in heterozygous sequences. The earlier protocols for human leukocyte antigen HLA‐DQB1 Sequencing‐Based Typing (SBT) frequently encounter preferential amplification of one of the alleles that can lead to unreliable sequences or even to allelic dropout. In our new approach, the quality of the exon 2 sequences, now including both alleles to the same extend, was achieved by amplifying the HLA‐DQB1*05/06 group into two groups by changing the common 3′ amplification primer. In combination with exon 3 this updated HLA‐DQB1 protocol provides a reliable approach for heterozygous sequencing.