bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of HLA class I alterations in tumors: choosing a strategy based on known patterns of underlying molecular mechanisms
Authors: Cabrera T. , Maleno I. , Collado A. , Lopez Nevot M. A. , Tait B. D. , Garrido F.
Published: April 2007

The application of peptide‐based immunotherapy in the treatment of cancer has known limitations in patients with loss or downregulation of human leukocyte antigen (HLA) class I expression on tumor cells. These alterations diminish the ability of cancer cells to present tumor peptides to T cells and therefore lead to failure of peptide‐based cancer vaccination. Abnormal expression of HLA class I molecules in malignant cells is a frequent event that ranges from total loss of class I molecules to partial loss of HLA‐specific haplotypes or alleles. Different mechanisms underlie these alterations and might require different therapeutic approaches. A complete characterization of molecular defects may suggest strategies for the selection and follow‐up of patients undergoing T‐cell based immunotherapy. Moreover, a precise identification of the mechanism leading to HLA class I defects in patients with cancer will help develop new, personalized patient‐tailored treatment protocols. Here, we describe several examples showing the necessity and feasibility of making detailed individual analysis of HLA alteration mechanisms based on previously described molecular patterns in different types of malignancy. We recommend using this approach, at least in some patients, to enhance the therapeutic benefit of cancer immunotherapy.
Canine DLA diversity: 1. New alleles and haplotypes
Authors: Kennedy L. J. , Barnes A. , Short A. , Brown J. J. , Lester S. , Seddon J. , Fleeman L. , Francino O. , Brkljacic M. , Knyazev S. , Happ G. M. , Ollier W. E. R.
Published: April 2007

The aim of this component was to establish the range of DLA diversity in as many dog breeds as possible. In particular, we wanted to collect breeds that had not previously been studied. Data were submitted of 937 dogs of over 80 different breeds, and these included 17 ‘new’ breeds. Twenty‐eight new alleles were identified including 21 DLA‐DRB1, 2 DLA‐DQA1 and 5 DLA‐DQB1 alleles. These occurred in many new haplotype combinations. One haplotype was identified that appeared to lack DQB1. Two other haplotypes carry two DQB1 genes. It was clear that each dog breed has a restricted range of DLA alleles and haplotypes, and no breed had all 88 haplotypes identified in this study.
Canine DLA diversity: 3. Disease studies
Authors: Kennedy L. J. , Barnes A. , Short A. , Brown J. J. , Seddon J. , Fleeman L. , Brkljacic M. , Happ G. M , Catchpole B. , Ollier W. E. R.
Published: April 2007

There are many millions of dogs worldwide, and these dogs have many different functions. The most obvious use is providing companionship, but there are also many working dogs, including guide dogs for the blind, hearing dogs, guard dogs and farm dogs, to mention a few. The health and welfare of these dogs is of great concern to dog owners, dog breeders and to those who use dogs in their work. Dogs spontaneously develop many diseases that are very similar to their human counterparts. Dogs may, therefore, provide exceptional animal models for such diseases. Identifying genetic markers in the dog may be easier than in humans, and may then provide useful information about genes that can be transferred to humans. This study looked for associations between DLA and two autoimmune diseases of the dog, diabetes and hypothyroidism. DLA associations were found for both of these diseases.
14th International HLA and Immunogenetics Workshop: Report from the reproductive immunology component
Authors: Varla‐Leftherioti M. , Keramitsoglou T. , Spyropoulou‐Vlachou M. , Papadimitropoulos M. , Kontopoulou‐Antonopoulou V. , Tsekoura C. , Sankarkumar U. , Paparistidis N. , Ghosh K. , Pawar A. , Vrani V. , Daniilidis M. , Parapanissiou E. , Diler A. S. , Carin M. , Stavropoulos‐Giokas C.
Published: April 2007

The aim of the study was to investigate whether human leukocyte antigen (HLA) allele sharing between partners or the maternal killer immunoglobulin‐like receptor (KIR) repertoire is associated with recurrent spontaneous abortion (RSA) and repeated implantation failure after in vitro fertilization (IVF)/embryo transfer. From a total population of 158 RSA couples, 40 couples with repeated implantation failures (IVF) and 81 control couples, reported by five different laboratories, analysis was performed for (a) HLA sharing in 50 RSA, 31 IVF and 31 control couples, (b) DQA1*0505 sharing/homozygosity among partners in 108 RSA, 40 IVF and 36 control couples, and (c) the women’s KIR repertoire in 46 RSA, 26 IVF and 36 control wives. RSA couples were divided into alloimmune aborter (RSAallo) and autoimmune aborter (RSAauto). The results oppose to the suggestion that increased HLA sharing per se or a limited maternal KIR repertoire predisposes to RSA or IVF failure. However, the observation of a slightly higher percentage of DQA1*0505 sharing in the RSAauto and the IVF group needs further investigation. The ratio of inhibitory to activating KIR (actKIR) was slightly lower in RSAallo and IVF women (1.9 vs 2.6 in controls), while in a high percentage of these women, the standard receptors of the KIR A haplotype were combined with actKIR/s of the haplotype B (66.6% and 45.4% vs 20% and 15.3% in RSAauto and control groups). This may suggest a possible involvement of actKIRs in embryo implantation and the maintenance of pregnancy and also requires further investigation.
An apportionment of human HLA diversity
Authors: Sanchez‐Mazas Alicia
Published: April 2007

In this study, we estimate the amount of human leukocyte antigen (HLA) genetic diversity in the global human population at three levels of population hierarchy: within populations; among populations within continents and among continents on large sets of HLA population data gathered during the last international histocompatibility and immunogenetics workshops and conferences. The results indicate that loci HLA‐A, B, C, DRB1, DQA1 and DQB1 exhibit a higher amount of diversity among individuals of the same population than observed for neutral polymorphisms (average diversity of 90.3% compared with 84.4%–87.6% for neutral DNA markers). On the other hand, the value (84%) obtained for HLA‐DPB1 is very similar to those observed for non‐HLA nuclear markers, in agreement with other results suggesting the neutrality of this locus. In addition to the results of the hierarchical analysis of variance, selective neutrality tests indicate that loci B, C and DRB1 are the most affected by balancing selection. However, one cannot discriminate between a direct selective effect acting on those loci or a general effect of associative overdominance acting over the large HLA region (in linkage disequilibrium) encompassing those loci.
Typing of potential and selected donors for transplant: methodology and resolution
Authors: Oudshoorn M. , Horn P. A. , Tilanus M. , Yu N.
Published: April 2007

The goal was to establish the best typing techniques and strategies for donors selected as potential donors for a specific patient. Complete sequence of exons 2 and 3 for class I and exon 2 for class II molecules by sequencing‐based typing was deemed the best technique in reducing problems with ambiguities and null alleles as well as the possibility to establish a completely automated system. Focusing on multiple approaches for typing was regarded as a better strategy than continued usage of serological methods although the latter technique was still considered to be useful by some for detection of null alleles. The patient and finally the selected donor, including the back‐up donor, should be typed for at the highest level and typing ambiguities should be resolved. In very difficult cases, race, haplotype information and allele frequency in the population should help to decide whether or not to resolve the ambiguity. Cellular techniques such as the cytotoxic T lymphocyte precursor test may help to choose between single class I mismatched donors in experienced laboratories only.
Immune response gene polymorphisms in unrelated donor hematopoietic cell transplantation
Authors: Malkki M. , Gooley T. , Dubois V. , Horowitz M. , Petersdorf E. W.
Published: April 2007

Immune response genes (IRG) play an important role in inflammation and control of infection after allogeneic transplantation. The International Histocompatibility Working Group (IHWG) in hematopoietic cell transplantation took a candidate gene approach to define the risks associated with genetic variation for a panel of well‐characterized IRG.
A community standard XML message format for sequencing‐based typing data
Authors: Maiers M.
Published: April 2007

An electronic messaging format has been developed and is proposed as a community standard. This format allows explicit representation of typing results for polymorphic immunogenetic gene systems such as killer cell immunoglobulin‐like receptor and human leukocyte antigen. Primary data in the form of Sequence Specific Oligonucleotide (SSO)/Sequence Specific Primer (SSP) reactivities and sequencing‐based typing sequences can be linked with nomenclature‐based results allowing complete representation of the permanent information.
Sequencing‐based typing identifies novel alleles due to single nucleotide polymorphisms in ‘conserved’ regions
Authors: Smith L. K. , Sayer D. C. , Whidborne R. S. , Christiansen F. T.
Published: April 2007

The Royal Perth Hospital laboratory has been using sequencing‐based typing for all HLA loci since 2002. In the period to October 2005, approximately 12,000 HLA A and HLA B, 5000 HLA C and DQB1, and 17,000 DRB1 requests have been processed. Twenty nine novel alleles have been identified in that time. These comprise 10 HLA‐A (including one null allele), five HLA‐B, six HLA‐C, six DRB1 (including a null allele), and one DQB1 novel allele. (At the time of identifying the DRB1 null allele, there were no other reported examples.) In addition, we have seen one example of a blast‐specific HLA‐A null allele. One HLA‐A allele (HLA‐A*0264) and one HLA‐B allele (HLA‐B*400104) were subsequently identified in other laboratories and submitted to the international ImMunoGeneTics project (IMGT) database.
Pilot study: assessment of interlaboratory variability of sequencing‐based typing DNA sequence data quality
Authors: Sayer D. C. , Goodridge D. M.
Published: April 2007

This pilot study showed that variability in the sequence quality scores exists within and between laboratories performing human leukocyte antigen typing by sequence‐based typing (SBT). It also showed that the base call score (BCS) system in Assign‐SBT is a useful tool for comparing sequence quality between laboratories.
Diversity of HLA‐DQA1 gene in the Korean population
Authors: Lee K. W. , Jung Y.‐A. , Oh D. H.
Published: April 2007

Genotype of the human leukocyte antigen (HLA)‐DQA1 locus was analyzed in Koreans (n= 467) using the 14th International Workshop protocol established to characterize the sequences of exons 1–4 of the gene. Unexpectedly, it appeared that the DQA1 (19 alleles) was more diverse than DQB1 (15 alleles) in the study population. DQA1*010201, DQA1*0303, DQA1*0103, and DQA1*0302 appeared to be major alleles exhibiting more than 10%. Among six allele groups, DQA1*01–*06, DQA1*01 showed highest diversity exhibiting seven different alleles. Analysis using maximum likelihood method showed numerous multi‐locus HLA haplotypes. High relative linkage disequilibrium values (RLD) of the two‐locus haplotypes and exclusive association of a specific DQA1 allele with a specific DRB1 and/or DQB1 alleles suggested tight linkage of DQA1 to DRB1 and DQB1. In HLA‐matching process for hematopoietic stem cell transplantation, however, DQA1 typing would be informative for individuals carrying specific DRB1 allele (DRB1*0802, DRB1*1201, or DRB1*1403) that could be associated with multiple DQA1 alleles in the study population. Information obtained in this study will be useful in medical and forensic areas as well as in anthropology.
Relevance of KIR gene matching in unrelated hematopoietic stem cell transplantations
Authors: Gagne K. , Busson M. , Balere‐Appert M. L. , Absi L. , Jollet I. , Bignon J.‐D. , Bois M. , Dormoy A. , Dubois V. , Gebuhrer L. , Loiseau P. , Masson D. , Moine A. , Perrier P. , Reviron D. , Charron D. , Raffoux C. ,   ARS 2000 FRM and FGM group
Published: April 2007

The aim of this collaborative study was to evaluate the impact of killer cell immunoglobulin‐like receptor (KIR) gene disparities on unrelated hematopoietic stem cell transplantations (HSCT) outcome. To address this question, we have determined the presence or absence of 14 functional KIR genes in HLA‐matched (n= 164) or HLA‐mismatched (n= 100) donor/recipient pairs and investigated whether KIR gene disparities had an impact on both the occurrence of acute graft‐vs‐host‐disease incidence and overall survival. In a univariate analysis, our preliminary results suggest a detrimental effect of a few KIR gene disparities on patient survival that should be avoided in unrelated HSCT.
Distribution of the killer cell immunoglobulin‐like receptors in Mexican Mestizos
Authors: Contreras G. , Aláez C. , Murguía A. , García D. , Flores H. , Gorodezky C.
Published: April 2007

Understanding the complex interaction between human leukocyte antigen (HLA) and killer immunoglobulin‐like receptor (KIR) requires study of both HLA and KIR diversity in the same population. The presence of KIR genes 2DL1, 2, 3, 4, 5, KIR3DL1, 3DL2, 3DL3, KIR2DS1, 2DS2, 2DS3, 2DS4, 2DS5, KIR3DS1, KIR3DP1, KIR2DP1 was determined in 54 unrelated Mexican Mestizo donors. The PCR sequence‐specific oligonucleotide probe One Lambda kit (Luminex) kindly given by J. Lee was used for typing. The software analyses the combination obtained for each of the five exons. Five controls (UCLA DNA exchange) were run as quality control. The gene frequency (GF) was calculated for the 16 KIR loci; the GF of individual genes was 100% for 2DL4, 3DL1, 3DL2, 3DL3, 3DP1. KIR2DL1 (76.43%), KIR2DL2 (37.64%), KIR2DL3 (76.43%), KIR2DL5 (29.29%), KIR3DS1 (23.02%), KIR2DS1 (21.83%), KIR2DS2 (37.64%), KIR2DS3 (50.93%), KIR2DS4 (86.93%), KIR2DS5 (29.29%), KIR2DP1 (86.39%). We observed similar frequencies with Caucasians and Mediterraneans, with exceptions: KIR3DL1 which was present in 100% Mexicans, ranged from 62% to 75% in Caucasians; 2DS3 (50.9%) vs 14–20% 2DS4 (86.39%) vs 65–79% and 2DS5 (29.29%) vs 11–18% in Caucasians. The finding of 23 phenotypes in 54 individuals accounting for both chromosomes, demonstrates the enormous diversity. We found 14 different combinations of stimulatory KIRs in the phenotypes; every subject had at least one stimulatory KIR; in all of them, 2DS4 existed except for one person who may have some new combination: 2DS2 2DS3. Extended family data will offer accurate and precise haplotypes to provide an insight on the significance of ethnic distribution and KIR repertoire.
Modelling KIR–HLA genotype disparities in type 1 diabetes
Authors: Van Der Slik A. R. , Alizadeh B. Z. , Koeleman B. P. C. , Roep B. O. , Giphart M. J.
Published: April 2007

We previously reported that a disparate distribution between killer cell immunoglobulin‐like receptor (KIR) and human leukocyte antigen (HLA) class 1 genes is associated with susceptibility to develop type 1 diabetes. Here we compare multiple models which reflect the combined genotype effects of combinations of functional inhibitory and activating KIRs in relation to HLA in an extended cohort of patients with juvenile‐onset type 1 diabetes and non‐diabetic control subjects. Our results suggest that autoimmunity in type 1 diabetes is mainly associated with a decrease in inhibitory KIR–HLA genotype combinations, while the influence of activating KIR genotypes seems redundant. However, logistic regression showed that activating KIR genotypes do influence the overall hierarchy of protection/susceptibility as reflected by composite inhibitory and activating KIR–HLA genotype models.
KIR receptors and HLA‐C in the maintenance of pregnancy
Authors: Flores A. C. , Marcos C. Y. , Paladino N. , Arruvito L. , Williams F. , Middleton D. , Fainboim L.
Published: April 2007

The present study demonstrated that patients who have recurrent spontaneous abortions (RSA) presented a decreased number of killer immunoglobulin‐like inhibitory receptors (KIR), in particular KIR2DL2. The KIR AA genotype was found increased in comparison with controls. Individuals AA will also be homozygous for 2DL3, which in contrast to 2DL2, show a weaker interaction with C1 ligands and therefore a weaker inhibition. The present study might support that in RSA patients, the balance between inhibitory and activating receptors present in natural killer cells is inclined toward an activating state that may contribute to pregnancy loss.
HLA‐E polymorphism in Amerindians from Mexico (Mazatecans), Colombia (Wayu) and Chile (Mapuches): evolution of MHC‐E gene
Authors: Arnaiz‐Villena A. , Vargas‐Alarcon G. , Serrano‐Vela J. I. , Reguera R. , Martinez‐Laso J. , Silvera‐Redondo C. , Granados J. , Moscoso J.
Published: April 2007

Human leukocyte antigen (HLA)‐E is a nonclassical class I (Ib) gene with a restricted polymorphism. Only eight DNA alleles and three proteins of this gene have been described and their frequencies analyzed in Caucasian, Oriental, Asian Indian, and Negroid populations. In the present study, HLA‐E polymorphism has been analyzed in six Amerindian and Mestizo populations from North and South America and compared with previously described populations. HLA‐E*0101 is the most frequent allele found in all populations except in Afrocolombian and Wayu Amerindians, in which blood group analyses show a high admixture with Caucasian and African populations. Mazatecan and Mapuche (two Amerindian groups from North and South America, respectively) presented similar HLA‐E frequencies, whereas Wayu Indians are more similar to the Afrocolombian population. The Mexican and Colombian Mestizo show similar allele frequencies to Amerindians with high frequencies of HLA‐E*0101 and HLA‐E*010302 alleles. Also, frequencies in Negroids and Asian Indians present a similar distribution of HLA‐E alleles. These data are in agreement with worldwide restricted polymorphism of HLA‐E because no new allele was detected in the six populations studied. The allelic frequencies show differences among Caucasian, Oriental, Mestizo and Indian populations. Ape major histocompatibility complex‐E allelism is also very restricted: common chimpanzee (one allele); bonobo (two alleles); gorilla (two alleles); orangutan (one allele); rhesus monkey (eight alleles); cynomolgus monkey (two alleles); and green monkey (two alleles).
HLA‐G levels in serum and plasma
Authors: Rudstein‐Svetlicky N. , Loewenthal R. , Horejsi V. , Gazit E.
Published: April 2007

Soluble human leukocyte antigen (HLA)‐G levels are in most cases higher in the plasma than in the serum obtained from the same individual. This is probably due to trapping of the protein during clot formation. In studies where soluble HLA‐G is quantified, it is therefore recommended that plasma or serum levels should be compared with the same blood product, namely, serum to serum and plasma to plasma. Because of possible gender differences in HLA‐G levels it is also recommended that this should be considered in the construction of a control group especially in studies where there is a preponderance of one of the sexes.
Quantification and identification of soluble HLA‐G isoforms
Authors: Rebmann V. , LeMaoult J. , Rouas‐Freiss N. , Carosella E. D. , Grosse‐Wilde H.
Published: April 2007

In order to clarify the diagnostic relevance of soluble human leukocyte antigen‐G (sHLA‐G) molecules, reliable methods for the measurement of sHLA‐G in various body fluids are of interest. Therefore, the aims of the ‘Wet‐Workshop for Quantification of Soluble HLA‐G’ held in Essen, Germany (at the Institute of Immunology, 18–20 October 2004) were to select and to validate HLA‐G‐specific enzyme‐linked immunosorbent assay (ELISA) formats and purified standard HLA‐G proteins, which can be easily generated and used as consensual references. We chose two ELISA formats, one for the simultaneous determination of shed HLA‐G1 + sHLA‐G5 (sHLA‐G1 + G5) and one for the exclusive detection of HLA‐G5 molecules. The first ELISA uses the antibody pair monoclonal antibody (mAb) MEM‐G/9 + anti‐β2‐microglobulin (β2m), whereas the latter uses mAbs 5A6G7 + W6/32. Purified and well‐defined HLA‐G5 protein derived from insect SF9 cells transfected with HLA‐G5 + human β2m served as standard reagent. Twenty‐five members of 13 international laboratories participated in the 3‐day Wet‐Workshop. The workshop demonstrated that the HLA‐G5 protein was equally detected by both ELISA formats allowing direct comparison of quantitative results obtained by these two ELISA formats, and that sHLA‐G1 + G5 and HLA‐G5 molecules, respectively, were specifically and reproducibly quantified by the two ELISA formats. The comparison of the two ELISA results obtained allows the conclusion that sHLA‐G1 and HLA‐G5 molecules can exist in the blood of healthy donors. Moreover, there was evidence for a novel soluble HLA‐G structure recognized by the mAbs 5A6G7 + W6/32 antibody combination but not by the one of mAb MEM‐G/9 + anti‐β2m.
Recurrent spontaneous abortions patients have more −14 bp/+14 bp heterozygotes in the 3′UT region of the HLA‐G gene in a Chinese Han population
Authors: Xue S. , Yang J. , Yao F. , Xu L. , Fan L.
Published: April 2007

Although human leukocyte antigen (HLA)‐G gene polymorphism is low, it may influence levels of protein expression and, in some cases, has been associated with pregnancy diseases. Apart from the 23 HLA‐G alleles, including a null allele known as HLA‐G*0105N, a 14‐bp deletion or insertion in the 3′UT region also contributes to the HLA‐G gene polymorphism. In order to discover any correlation between the 14‐bp deletion polymorphism and pregnancy diseases, we isolated the genomic DNA from 24 recurrent spontaneous abortions (RSA) patients and 88 normal fertile control individuals using the salted out method. Exon‐8 of HLA‐G gene of the two groups was amplified by polymerase chain reaction, respectively, and analyzed by electrophoresis on 9% nondenaturing polyacrylamide gel and stained with ethidium bromide. Differences between the two groups were compared using the χ2 test. The results were there was no significant difference in allelic frequencies of 14‐bp deletion polymorphism between normal control and RSA patients; frequency of −14 bp/+14 bp heterozygotes was significantly increased in RSA patients as compared with normal fertile controls. Our results are similar to a study of Indian women but contradictory to a study of Danish women. This discrepancy may be due to ethnic differences.
HLA‐G polymorphism and evolution
Authors: Arnaiz‐Villena A. , Martinez‐Laso J. , Serrano‐Vela J. I. , Reguera R. , Moscoso J.
Published: April 2007

Six proteins, one null allele and 22 human leukocyte antigen (HLA)‐G alleles were found in humans. Bonobo, chimpanzee and gorilla only show one allele and orangutan shows five alleles. All Cercopithecus alleles show stop codons at position 164 (Macaca mulatta with seven DNA alleles, Macaca fascicularis with seven DNA alleles and Cercopithecus aethiops with three DNA alleles). Cotton‐top tamarin New World monkeys showed 20 DNA and protein alleles; the major histocompatibility complex (MHC)‐G New World sequences seem to be closer to MHC‐E and lack typical MHC‐G primates intron 2‐specific deletion. This seems to suggest that MHC‐G genes in New World primates are not orthologous and that their function may be similar to that of classical presenting MHC genes.
Mycobacterial infections: PARK2 and PACRG associations in leprosy
Authors: Schurr E. , Alcais A. , Singh M. , Mehra N. , Abel L.
Published: April 2007

An overview of investigations indicating an important role of host genetics, both major histocompatibility complex (MHC) and non‐MHC, in leprosy.
Association of variants in the IL12B gene with leprosy and tuberculosis
Authors: Morahan G. , Kaur G. , Singh M. , Rapthap C. C. , Kumar N. , Katoch K. , Mehra N. K. , Huang D.
Published: April 2007

There is a great range in outcomes after mycobacterial infections, and this is probably due to individual variation in immune responses. One of the key cytokine regulators of the immune response is interleukin (IL‐) 12. The IL12B gene encodes the p40 chain of both IL‐12 and IL‐23 and it has two major variant sites at which different alleles are associated with increased levels of gene expression and with susceptibility to a range of immune‐related diseases. We hypothesized that IL12B variants associated with increased expression would be as associated with susceptibility to persistent mycobacterial infection. We tested this hypothesis by genotyping Indian subjects, having either leprosy or tuberculosis (TB), as well as ethnically matched controls. Subjects with leprosy were less likely to have the 3’UTR genotype associated with lower IL12B expression (P= 0.001). Subjects with TB were not only more likely to have the high‐expressing IL12B promoter genotype (P= 0.01) but also more likely to have this in the same haplotype with the high expressing 3’UTR allele (P= 0.0009). These results suggest these infectious diseases may be improved by modulating IL‐l2p40 production.
Influence of inhibitory killer immunoglobulin‐like receptors and their HLA‐C ligands on resolving hepatitis C virus infection
Authors: Rauch A. , Laird R. , McKinnon E. , Telenti A. , Furrer H. , Weber R. , Smillie D. , Gaudieri S. ,   the Swiss HIV Cohort Study
Published: April 2007

An estimated 2%–3% of the world’s population is chronically infected with hepatitis C virus (HCV) and this is a major cause of liver disease worldwide. Following acute infection, outcome is variable with acute HCV successfully resolved in some individuals (20%–30%), but in the majority of cases the virus is able to persist. Co‐infection with human immunodeficiency virus has been associated with a negative impact on the course of HCV infection. The host’s immune response is an important correlate of HCV infection outcome and disease progression. Natural killer (NK) cells provide a major component of the antiviral immune response by recognising and killing virally infected cells. NK cells modulate their activity through a combination of inhibitory and activatory receptors such as the killer immunoglobulin‐like receptors (KIRs) that bind to human leukocyte antigen (HLA) Class I molecules. In this workshop component, we addressed the influence of KIR genotypes and their HLA ligands on resolving HCV infection and we discuss the implications of the results of the study of Lopez‐Vazquez et al. on KIR and HCV disease progression.
Interactions of temperature and photoperiod in the control of flowering of latitudinal and altitudinal populations of wild strawberry (Fragaria vesca)
Authors: Heide Ola M. , Sønsteby Anita
Published: April 2007

Floral induction and development requirements of a range of latitudinal and altitudinal Norwegian populations of the wild strawberry Fragaria vesca L. have been studied in controlled environments. Rooted runner plants were exposed to a range of photoperiods and temperatures for 5 weeks for floral induction and then transferred to long day (LD) at 20°C for flower development. A pronounced interaction of temperature and photoperiod was shown in the control of flowering. At 9°C, flowers were initiated in both short day (SD) and LD conditions, at 15 and 18°C in SD only, whereas no initiation took place at 21°C regardless of daylength conditions. The critical photoperiod for SD floral induction was about 16 h and 14 h at 15 and 18°C, respectively, the induction being incomplete at 18°C. The optimal condition for floral induction was SD at 15°C. A minimum of 4 weeks of exposure to such optimal conditions was required. Although the populations varied significantly in their flowering performance, no clinal relationship was present between latitude of origin and critical photoperiod. Flower development of SD‐induced plants was only marginally advanced by LD conditions, while inflorescence elongation and runnering were strongly enhanced by LD at this stage. The main shift in these responses took place at photoperiods between 16 and 17 h. Unlike all other populations studied, a high‐latitude population from 70°N (‘Alta’) had an obligatory vernalization requirement. Although flowering and fruiting in its native Subarctic environment and after overwintering in the field in south Norway, this population did not flower in the laboratory in the absence of vernalization, even with 10 or 15 weeks of exposure to SD at 9°C. Flowering performance in the field likewise indicated a vernalization requirement of this high‐latitude population.
Ocular manifestations of natural canine monocytic ehrlichiosis (Ehrlichia canis): a retrospective study of 90 cases
Authors: Komnenou Anastasia A. , Mylonakis Mathios E. , Kouti Vassiliki , Tendoma Lina , Leontides Leonidas , Skountzou Eugenia , Dessiris Angelos , Koutinas Alex F. , Ofri Ron
Published: April 2007

Objective  To investigate the spectrum, prevalence and treatment response rate of ocular manifestations associated with natural canine monocytic ehrlichiosis (CME) due to Ehrlichia canis.

Methods  The medical records of 90 dogs that were admitted for primary ocular problems and reacted positive for E. canis serum antibodies were reviewed. All the dogs were treated with oral doxycycline. In 79 dogs, a combination of systemic corticosteroids and/or topical anti‐inflammatory, mydriatics/cycloplegics and antibacterial agents were applied.

Results  The dogs ranged from 0.5 to 15 years in age; 55 were male and 35 female. A total of 19 breeds were represented. In the majority of dogs, ocular abnormalities were noticed in conjunction with other CME‐induced clinical signs. In 30/90 dogs, ophthalmic signs were the sole presenting complaint. Unilateral (22/90, 24.5%) and bilateral (68/90, 75.5%) uveitis was the most common ophthalmic diagnosis and was classified as anterior, posterior or panuveitis in 58 (64.5%), 8 (8.9%) and 24 (26.6%) of the dogs, respectively. Bilateral uveitis was significantly more common than unilateral uveitis (P < 0.0001), and anterior significantly more common than posterior uveitis (P < 0.0001) or panuveitis (P < 0.0001). In addition, corneal ulceration (12/90, 13.3%), necrotic scleritis (10/90, 11.1%), low tear production (8/90, 8.9%) and orbital cellulitis (3/90, 3.3%) were seen. Of the 45 (50%) dogs with a satisfactory follow‐up, 25 (55.5%), 11 (24.5%), and 9 (20%) showed complete, partial and poor response to treatment, respectively. The number of dogs exhibiting complete resolution of the ocular manifestations was significantly higher than those with partial (P < 0.0001) or poor (P < 0.0001) response.

Conclusions  CME should be considered a major differential for a wide range of ocular manifestations exhibited by dogs residing in the endemic areas of the disease. Anterior bilateral uveitis appears to be the most prevalent ocular lesion and a favorable outcome to systemic and topical treatment may be expected in the majority of the affected dogs.
Evaluation of the clinical efficacy of subconjunctival injection of clindamycin in the treatment of naturally occurring infectious bovine keratoconjunctivitis
Authors: Senturk Sezgin , Cetin Cengiz , Temizel Mutlu , Ozel Ebru
Published: April 2007

Objective To determine the clinical efficacy of subconjunctival injection of clindamycin in the treatment of naturally occurring infectious bovine keratoconjunctivitis (IBK).

Animals studied Clinically, out of 81 animals examined, 46 were found to be suffering from IBK of variable severity. The ocular secretions were collected and cultured forMoraxella bovis. The study included 36 Holstein cattle from whichM. Boviswas isolated. These animals ranged between 4 and 28 months of age.

Procedures The severity of the clinical findings were scored as normal, mild, moderate, and severe. Clindamycin was injected subconjunctivally at a total dose of 150 mg (1 mL), once daily for 3 days to the test group (n = 18); isotonic saline solution (1 mL) was administered to the control group. After treatment, all cattle were re‐examined and clinical response was evaluated on days 3, 7 and 15 post‐treatment.

Results Compared with the control group and prior to treatment, all active lesions such as blepharospasm, epiphora, photophobia, chemosis, corneal edema, and corneal ulceration were generally resolved by day 15 after subconjunctival injection of clindamycin. Severity of IBK lesions increased on days 3 and 7, compared to baseline in the control group administered isotonic saline solution.

Conclusions The results of this study suggest that subconjunctival injection of clindamycin is effective in the treatment of naturally occurring infectious bovine keratoconjunctivitis.
Maximizing anticholinergic therapy for overactive bladder: has the ceiling been reached?
Authors: MacDiarmid Scott A.
Published: April 2007

Urinary incontinence affects an estimated 20–33% of adults the USA and 55% of the country’s elderly [1], having a more substantial impact on the physical and mental dimension of quality of life than other common chronic diseases. Muscarinic receptor antagonists, including oxybutynin, tolterodine, trospium chloride, darifenacin, and solifenacin, are front‐line therapies for overactive bladder (OAB), with an efficacy of 65–75% in reducing major symptoms. Strategies to increase the therapeutic index have included behavioural therapy, flexible dosing, and dose escalation, as well as newer formulations that reduce anticholinergic side‐effects. Among approved OAB agents, the oxybutynin transdermal‐delivery system has been associated with a lower incidence of dry mouth than immediate‐ and extended‐release formulations of traditional agents. With a low propensity for drug interactions and dry mouth, it is a likely candidate for older patients taking multiple medications. The transdermal patch bypasses systemic and first‐pass metabolism, avoiding higher plasma concentrations of the active metabolite (N‐desethyloxybutynin) thought to be associated with dry mouth symptoms. Anticholinergics have a significant role to play in the management of OAB; newer drugs targeted toward muscarinic receptors, and novel delivery systems, continue to increase the therapeutic index for this condition.
The prognostic significance of p53, Ki‐67, epithelial cadherin and matrix metalloproteinase‐9 in penile squamous cell carcinoma treated with surgery
Authors: Zhu Yao , Zhou Xiao Y. , Yao Xu D. , Dai Bo , Ye Ding W.
Published: April 2007

OBJECTIVE

To evaluate the prognostic significance of p53, Ki‐67, epithelial cadherin (E‐cadherin) and matrix metalloproteinase‐9 in primary penile cancer, as the presence of lymph node metastasis and long‐term survival are hard to define in penile squamous cell carcinoma.

PATIENTS AND METHODS

Paraffin‐embedded primary tumour samples were obtained from 73 Chinese patients who had penile amputation and regional lymphadenectomy. The expression of molecular markers was determined by immunohistochemistry. Logistic regression was used to identify factors associated with lymph node metastasis, and a Cox proportional‐hazards model was used to measure cancer‐specific survival (CSS).

RESULTS

Thirty (41%) patients presented with nodal disease and the 3‐year CSS rate for all patients was 72%. Lymph node metastasis was significantly correlated with tumour stage, histological grade, lymphatic and vascular embolization, and the expression of p53, Ki‐67 and E‐cadherin. By multivariate analysis, tumour embolization and the expression of p53 were independent predictors of metastasis. Survival analysis showed that the expression of p53 was an independent prognostic factor for CSS. In stage T1 tumours, high expression of p53 was significantly associated with metastasis and poor survival.

CONCLUSION

Lymphatic and vascular embolization, and p53 immunoreactivity, are helpful in establishing the probability of lymph node metastasis. The expression of p53 is an independent predictor of CSS in Chinese patients with penile cancer. In stage T1 tumours, p53 staining is an important variable determining the prognosis and treatment outcome.
Pelvic floor muscle training to improve urinary incontinence after radical prostatectomy: a systematic review of effectiveness
Authors: MacDonald Roderick , Fink Howard A. , Huckabay Chad , Monga Manoj , Wilt Timothy J.
Published: April 2007

OBJECTIVE

To evaluate the effectiveness of pelvic floor muscle training (PFMT) for treating urinary incontinence (UI) after radical prostatectomy (RP) by reviewing evidence from randomized trials.

METHODS

Randomized trials published in English were included if they involved men with UI after RP and compared PFMT with a control group. Data were abstracted onto a standardized form using a prospectively developed protocol.

RESULTS

Eleven trials randomizing 1028 men (mean age 64 years) met the inclusion criteria; the duration of the trials was 3–12 months. One trial of 300 men found that those assigned to PFMT achieved continence more quickly (after 1, 3 and 6 months) than men not assigned to PFMT. Men receiving biofeedback‐enhanced PFMT were more likely to achieve continence or have no continual leakage than those with no training within 1–2 months after RP (relative benefit increase 1.54; 95% confidence interval 1.01–2.34; four trials reporting). The relative benefit increase (1.19, 0.82–1.72; five studies) was no longer significant after 3–4 months. Biofeedback‐enhanced PFMT was comparable to written/verbal PFMT instruction. Extracorporeal magnetic innervation (ExMI) and electrical stimulation (ES) were found to be initially (within 1–2 months) more effective than PFMT in one trial, but there were no significant differences between groups at ≥ 3 months.

CONCLUSION

Based on available evidence, PFMT with or without biofeedback enhancement hastens the return to continence more than no PFMT in men with UI after RP. Additional trials are needed to confirm whether ExMI and ES are effective conservative treatment options.
DID THE MARKET‐CLEARING POSTULATE PRE‐EXIST NEW CLASSICAL ECONOMICS? THE CASE OF MARSHALLIAN THEORY*
Authors: DE VROEY MICHEL
Published: April 2007

Have new classicists invented market clearing or have they just rehabilitated it? This is the question addressed in the present paper. It is generally agreed that market clearing underpins Walrasian theory, so my exploration is limited to the question of whether this is also true for Marshallian theory. I will claim that this is broadly the case: once Marshallian theory is properly reconstructed, it exhibits market clearing as a constantly present result. Still, an important difference between market clearingà laWalras and market clearingà laMarshall exists: in the former market clearingisequilibrium, while in the latter market clearing can coexist with disequilibrium. Next, I investigate whether my conclusion extends to the labour market. Again the conclusion reached is affirmative both for Marshall's theory and for present‐day Marshallian models. As to the latter, I take Friedman's Phillips curve model as a case study. I show that this is a market‐clearing model in which, strictly speaking, there is no place for the concept of unemployment—quite an ironical result for the paper that introduced the notion of the natural rate of unemployment!
Antimicrobial activity of enterococci strains isolated from white cheese
Authors: HAJIKHANI RASTA , BEYATLI YAVUZ , ASLIM BELMA
Published: April 2007

Twelve strains of enterococci isolated from white cheese samples obtained from different regions of Turkey were screened for their antimicrobial activity against some Gram‐positive and Gram‐negative food‐borne pathogens and contaminating bacteria, also against themselves and some other lactic acid bacteria (LAB), including some species of lactococci, lactobacilli and Leuconostoc. Antimicrobial activity was confirmed for all 12 strains, including six Enterococcus faecium, two Enterococcus faecalis and four Enterococcus durans. Antimicrobial agents produced by these enterococci exhibited a spectrum of activity, which is mainly directed against food‐borne pathogens, specially Listeria monocytogenes and Bacillus cereus and some other Bacillus spp. and also some enterococci. Tested LAB was insensitive to inhibitory agents produced by them.
Survival of Escherichia coli O157:H7 in yogurt drink, plain yogurt and salted (tuzlu) yogurt: Effects of storage time, temperature, background flora and product characteristics
Authors: AKDEMİR EVRENDİLEK GÜLSÜN
Published: April 2007

The survival of Escherichia coli O157:H7 at 4 and 22°C in yogurt drink, plain yogurt and salted yogurt (yogurt native to Hatay, Turkey) was studied. Total aerobic plate count (TPC), total mould and yeast count, pH and titratable acidity during the storage period were measured. pH and TPC count of the samples at 22°C were significantly higher than those of samples at 4°C (P < 0.01). E. coli O157:H7 survived in the products at both 4 and 22°C, whereas survival of E. coli O157:H7 was significantly lower at 4°C than at 22°C (P < 0.05). Multiple linear regression models were used to determine factors affecting the survival of E. coli O157:H7.
Functional attributes of native and thermized sour and sweet whey†
Authors: SHON JINHAN , HAQUE ZAHUR U
Published: April 2007

The functional attributes of sour (cottage) and sweet (Edam and Cheddar) whey powders and the effect of thermization (80°C/30 min) were investigated. Solubility of sour whey was significantly lower and oil‐holding capacity was higher than that of sweet whey samples. Thermization significantly enhanced thermostability (TS) of all powders, though solubility and emulsifying and foaming properties were depressed. Enhancement of TS was best demonstrated at acidic pH values of 3.0 and 4.5, where TS increased by 57 and 53%, 181 and 167%, and 31 and 48%, for cottage, Edam, and Cheddar, respectively. Thermization may be used to manufacture pasteurization and retort stable whey powders.
Heat sensitivity of Mycobacterium avium ssp. paratuberculosis in milk under pilot plant pasteurization conditions†
Authors: LYNCH DAVID , JORDAN KIERAN N , KELLY PHILLIP M , FREYNE THOMAS , MURPHY PATRICK M
Published: April 2007

Raw cow's milk inoculated with four laboratory strains (102−105 cfu/mL) of Mycobacterium avium ssp. paratuberculosis (Map) was pasteurized in a custom designed pilot plant pasteurizer having a maximum throughput of 580 L/h under turbulent flow conditions. Following 16 pasteurizer trials none of the Map strains survived high‐temperature short‐time conditions (72.5°C × 27 s) whether milk was homogenized or not. Two dairy herds containing animals which were faecal positive for Map were sourced and milk was collected for pasteurization studies. Milk collected from one herd on five occasions in the autumn did not contain any detectable Map organisms, and the second herd that was sampled on only one occasion in early winter was shown to contain Map at low concentration. Map was not detected in any of these milks following pasteurization at 72.5°C for 27 s. Two natural isolates of Map inoculated into milk were likewise inactivated on pasteurization.
Threatened Peripheral Populations in Context: Geographical Variation in Population Frequency and Size and Sexual Reproduction in a Clonal Woody Shrub
Authors: YAKIMOWSKI SARAH B. , ECKERT CHRISTOPHER G.
Published: April 2007

Abstract:  Geographically peripheral populations of widespread species are often the focus of conservation because they are locally rare within political jurisdictions. Yet the ecology and genetics of these populations are rarely evaluated in a broader geographic context. Most expectations concerning the ecology and evolution of peripheral populations derive from the abundant‐center model, which predicts that peripheral populations should be less frequent, smaller, less dense, and have a lower reproductive rate than central populations. We tested these predictions and in doing so evaluated the conservation value of peripheral populations for the clonal shrub Vaccinium stamineum L. (Ericaceae, deerberry), which is listed as threatened in Canada. Based on 51 populations sampled from the center to the northern range limits over 2 years, population frequency and size declined toward the range limit, but ramet density increased. Sexual reproductive output varied widely among populations and between years, with many populations producing very few seeds, but did not decline toward range margins. In fact seed mass increased steadily toward range limit, and this was associated with faster germination and seedling growth, which may be adaptive in seasonal northern environments. Our results did not support the prediction that clonal reproduction is more prevalent in peripheral populations or that it contributed antagonistically to the wide variation in seed production. Peripheral populations of V. stamineum are as productive as central populations and may be locally adapted to northern environments. This emphasizes the importance of a broad geographical perspective for evaluating the ecology, evolution, and conservation of peripheral populations.
Population Adaptive Index: a New Method to Help Measure Intraspecific Genetic Diversity and Prioritize Populations for Conservation
Authors: BONIN AURELIE , NICOLE FLORENCE , POMPANON FRANÇOIS , MIAUD CLAUDE , TABERLET PIERRE
Published: April 2007

Abstract:  In conservation biology genetic diversity is recognized as an important criterion to consider when prioritizing populations for protection. Today, population genomics offers the opportunity to evaluate both neutral and adaptive components of genetic diversity directly at the genome level with molecular tools. By screening the genome with many genetic markers, it is possible to detect loci supposedly under natural selection and thus of adaptive significance. We devised a new diversity index, the population adaptive index (PAI), which accounts for the adaptive value of the population it refers to. To estimate this index, we performed a genome scan with amplified fragment length polymorphism markers to identify neutral and selected loci in several populations of a widespread amphibian (common frog, Rana temporaria) and a threatened plant (Austrian dragonhead, Dracocephalum austriacum L.). We then investigated four different conservation strategies aimed at protecting the maximum amount of genetic diversity (neutral or selected). In particular we explored the relevance of the principle of complementarity, usually applied to the protection of species, in the management of intraspecific diversity. This principle advocates the conservation of sets of units that together maximize the species' or genetic diversity, which is in opposition to the traditional approach of targeting populations that are the most diverse individually. Four major conclusions emerged from these results. First, the PAI seemed to be a valuable index to evaluate the adaptive diversities within populations. Second, in the two species, the neutral and adaptive diversities within and among populations were not correlated, so conservation strategies based on the neutral and adaptive indexes would not select the same populations for protection. Third, because of its efficiency in conserving genetic diversity, the principle of complementarity deserves to be used more often for this purpose. Fourth, when neutral and adaptive results conflict, additional arguments (e.g., demography, ecology, and geographic proximity) should be considered together with levels of genetic diversity to determine a conservation strategy.