bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple mechanisms underlie HLA dysregulation in cervical cancer
Authors: Brady C.S. , Bartholomew J.S. , Burt D.J. , Duggan‐Keen M.F. , Glenville S. , Telford N. , Little A‐M. , Davidson J.A. , Jimenez P. , Ruiz‐Cabello F. , Garrido F. , Stern P.L. 
Published: March 2003

Abstract:The consistent dysregulation of HLA expression in cervical neoplasia is likely to influence the natural history of the disease and prospects for cell‐mediated vaccine therapies. We have studied the underlying mechanisms in eight new cervical cancer cell lines derived from primary tumour biopsies. At least five independent mechanisms leading to changes in HLA expression were seen: HLA class I allelic transcription but no protein; abnormal HLA class I allelic transcription; no HLA‐B locus transcription; loss of heterozygosity (LOH); no γIFN‐mediated upregulation of HLA class I expression, and/or no interferon‐gamma (γIFN)‐mediated HLA class II induction. These were evident in different combinations in 7/8 cell lines showing that multiple, mostly irreversible mechanisms not overridden by γIFN, are responsible for HLA dysregulation in cervical neoplasia. Point mutations were responsible for lack of HLA‐A2 expression in two cases. In cell line 808, the mutation encodes a stop codon in exon 3; in cell line 778, mutation of the first intron acceptor site leads to use of an alternative AG site in exon 2, resulting in a frameshift and a stop codon after the translation of only 38 amino acids. Tumour cells showing specific HLA class I loss may have selective advantage in the face of tumour‐specific cytotoxic T cells (CTL). Such immune escape mechanisms present a major obstacle for the success of CTL‐mediated therapies in cervical cancer.
Novel HLA‐B*15 alleles identified in potential marrow donors
Authors: Williams T.M. , Wu J. , Bassinger S. , Montoya G.D. , Yee J. , Griffith B.B. , Kearns J. , McKeen M. , Birkos S. , Gourley I.S. , Kamoun M. 
Published: March 2003

Abstract:Several methods for low‐resolution class I typing of potential bone marrow donors are available. The National Marrow Donor Program® (NMDP) has initiated pilot projects for large‐scale DNA‐based class I typing to initially characterize donors. Sequence‐specific oligonucleotide probe hybridization and sequence‐specific primer polymerase chain reaction (PCR) screening of 3,500 NMDP potential donors suggested the presence of variants of known HLA‐B*15 variants in 3 donors. PCR products encompassing HLA‐B locus exons 1 through 3 were prepared and subcloned. Sequencing revealed 3 alleles differing from known HLA‐B*15 alleles by nucleotide substitutions resulting in predicted novel HLA‐B antigens. The new alleles occur in distinct ethnic groups. These findings further illustrate the substantial genetic variation present at the HLA‐B locus within human populations ( Note).
Serological and nucleotide sequence analysis of HLA‐A*6812
Authors: Faé I. , Gleißner B. , Kriks D. , Leitner D. , Fischer G.F. 
Published: March 2003

Abstract:We describe a novel HLA‐A allele, HLA‐A*6812. HLA‐typing of a patient was performed by serology and by DNA‐based analyses. Cloning and sequencing of exons 2 and 3 revealed that the genotype consisted of a common HLA‐A*0101 allele and the novel HLA‐A*6812 allele. HLA*6812 is identical to HLA‐A*68012 except for a single non‐synonymous nucleotide substitution leading to an exchange of a threonine to an isoleucine residue at position 142 of the HLA‐class I alpha chain. The allele was also found in the patient’s mother. The novel HLA‐A68 molecule is recognised by some but not all of our HLA‐A28‐specific sera. These results confirm that position 142 is important for the serological properties of the HLA‐A molecule ( Note).
Soluble HLA‐DR antigen levels in serum correlate with rheumatoid arthritis disease activity and the presence of disease‐associated epitopes
Authors: Verbruggen L.A. , Dumarey N. , Van de Velde H. , Rebmann V. , Flament J. , Van Wayenberge C. , Grosse‐Wilde H. , Demanet C. 
Published: March 2003

Acknowledgments:This study was supported by a grant from the Belgian Red Cross. The authors thank Prof. W. Duquet for valuable help with the statistical analysis of the results.Abstract:We investigated correlations between soluble HLA‐DR (sHLA‐DR) molecules and several clinical, biological and genetic parameters associated with rheumatoid arthritis (RA) disease activity. Serum sHLA‐DR concentrations were determined in 146 samples from 89 RA patients by an ELISA format, using an antibody combination of mouse and rat monoclonal anti‐human HLA‐DR antibodies. The mean sHLA‐DR serum level in RA patients was significantly increased with 277±19 ng/ml compared to 142±13 ng/ml of 80 healthy controls (P<0.001). In ascending order of significance, correlations were found between serum sHLA‐DR and EULAR swelling and pain scores, Waaler‐Rose, RA factor, ESR and CRP (P=0.025 to P<0.001). High sHLA‐DR levels were defined above 374 ng/ml that was the 95% confidence interval of the controls. Thirty‐seven blood samples (25%) in 31 RA patients were above this level. The EULAR pain and swelling scores, erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP) and RA factor were higher (P=0.044 to P<0.001) at the moment of high sHLA‐DR concentrations, compared to the lower concentrations. Higher disease activity was further found in groups of RA patients respectively heterozygous or homozygous for the disease‐associated epitope (Q)R/KRAA within the HLA‐DRB1 chain, compared to the group without this epitope (P<0.017 for part of the results). Likewise, sHLA‐DR was respectively 169±17 (no disease associated epitope), 324±34 (heterozygous) and 442±69 ng/ml (homozygous for the disease‐associated epitope on HLA‐DRB1 alleles) (P<0.017). In conclusion, this study shows significant correlations between serum sHLA‐DR levels and RA disease activity parameters, as well as increased sHLA‐DR in patients with disease‐associated epitope on HLA‐DRB1 alleles.
Sequence of a new class I null allele within the HLA‐B44 specificity
Authors: Bettens F. , Tiercy J.‐M. 
Published: March 2003

Acknowledgments:We thank the blood donor ALBA and her mother for their cooperation to this study. We also thank B. Kervaire and R. Zanone for expert technical assistance. This work was supported by the Swiss National Science Foundation (grant no. 32–52061.97 and no. 31–57557.99).Abstract:A new HLA class I null allele has been identified within the B44 group by combined serological and molecular typing of a blood donor. Based on full‐length cDNA sequencing, this novel HLA‐B*4419N allele was found to differ from B*4402 by one single base pair deletion at position 7 of exon 1 which results in a stop at codon 19. This mutation was confirmed by polymerace chain reaction‐sequence‐specific oligonucleotide probe (PCR‐SSOP) hybridization on genomic DNA. Based on family typing, this new allele segregates with the haplotype A*01‐B*4419N‐Cw*0501‐DRB1*1301‐DRB3*0101. Since nonsense codons are generally associated with increased mRNA decay, we investigated B*4419N mRNA by semi‐quantitative reverse transcriptase (RT)‐PCR and by cDNA cloning efficiency. Comparison of B*4419N cDNA to B*4402 control cDNA and to B35 cDNA levels in the same donor, as well as the analysis of cloned inserts, revealed that the exon 1 mutation did not significantly influence B*4419N steady‐state mRNA.
Rapid identification of minor histocompatibility antigen HA‐1 subtypes H and R using fluorescence‐labeled oligonucleotides
Authors: Kreiter S. , Wehler T. , Landt O. , Huber C. , Derigs H.‐G. , Heß G. 
Published: March 2003

Acknowledgments:We thank Brigitte Schuch and Karola Schmidt for excellent technical assistance. This work was supported by a grant of the Deutsche Krebshilfe (Nr. 70‐2427 and Nr. 70‐2428).Abstract:Donor‐recipient disparitiy of the minor histocompatibility antigen HA‐1 is relevant for the development of graft‐versus‐host disease after HLA‐matched sibling allogeneic bone marrow transplantation in HLA‐A*0201‐positive individuals. Two different alleles of HA‐1 with a single amino acid polymorphism have been identified. Here we describe a time‐ and cost‐efficient method for HA‐1 typing of genomic DNA, using site‐specific hybridization probes with the LightCycler. This method was compared with standard techniques as sequencing or allele‐specific polymerase chain reaction (PCR) and proved to be specific, reliable and reproducible. We conclude that HA–1‐subtyping using fluorescent‐labeled oligonucleotides represents a attractive method for the screening of samples before allogeneic transplantation in HLA‐A*0201‐positive individuals.
Further diversity at HLA‐A and ‐B loci identified in Afro‐Caribbean potential bone marrow donors
Authors: Cox S.T. , McWhinnie A.J. , Koester R.P. , Heine U. , Holman R. , Madrigal J.A. , Little A.‐M. 
Published: March 2003

Abstract:Two novel HLA‐A and three novel HLA‐B alleles were identified within a group of Afro‐Caribbean individuals who were recruited as potential donors for the Anthony Nolan Bone Marrow Trust Register. HLA typing was performed on DNA extracted from peripheral blood mononuclear cells using sequence‐specific oligonucleotide (SSO) probes for HLA‐A and ‐B loci. Eight individuals analysed exhibited hybridisation patterns for which a type could not be assigned. DNA from these individuals was further typed by two methodologies: direct sequencing of PCR products and reference strand conformation analysis (RSCA). The direct sequencing results allowed the identification of new alleles but did not allow confirmation of the cis/trans orientation of the new sequence motifs identified. RSCA analysis confirmed the results obtained by SSO and direct sequencing and in addition confirmed the cis/trans orientation of the new sequences. One individual possesses a new A*30 allele – A*3008 and two individuals possess an identical new A*74 allele – A*7404. The three novel HLA‐B alleles were identified in three individuals: B*0812, B*1554 and B*4503 respectively. For the remaining two samples, A*2612 was identified. At present Caucasoid individuals, and therefore Caucasoid phenotypes, are predominantly represented on the various different volunteer bone marrow donor registries. The examples presented here highlight the potential for identification of further polymorphisms within the HLA system as more individuals from the much‐needed ethnic minorities are recruited onto bone marrow donor registers.
A novel HLA allele, B*4104, identified in a cord blood donor
Authors: Turner D.M. , Vlachos G. , Cavanna S.L. , Brown J. , Brown C. , Navarrete C.V. 
Published: March 2003

Abstract:Results from a number of HLA typing methods prompted the DNA sequencing (SBT) of a cord blood sample at the HLA‐B locus. A novel HLA‐B allele, B*4104, was identified. This was confirmed by sequencing the mother of the cord blood unit for HLA‐B (Note).
Changes in activity of antioxidative enzymes in wheat (Triticum aestivum) seedlings under cold acclimation
Authors: Scebba Francesca , Sebastiani Luca , Vitagliano Claudio 
Published: March 2003

Activated oxygen species such as superoxide radicals, singlet oxygen, hydrogen peroxide and hydroxyl radicals can be produced in plants exposed to low, non‐freezing, non‐injurious temperatures. To prevent or alleviate oxidative injury, plants have evolved several mechanisms which include scavenging by natural antioxidants and enzymatic antioxidant systems such as superoxide dismutases, catalase and peroxidases.Although overproduction of hydrogen peroxide and increased tolerance to oxidative stress can be induced in wheat by low‐temperature treatments, data concerning changes in the enzymatic antioxidant systems are almost absent.With the aim to provide this information, antioxidant enzyme (superoxide dismutases, catalase and peroxidases) activities were analysed in leaves and roots of Triticum aestivum cvs Brasilia (frost resistant in field) and Eridano (less frost resistant in field) seedlings grown at day/night temperatures of 24/22°C (control treatment) and 12/5°C (low‐temperature treatment).Our data showed that superoxide dismutase activities were unaffected by low‐temperature treatment both in leaves and roots. Catalase activity in leaves and roots was decreased in 12/5°C‐grown seedlings, but Brasilia maintained higher catalase activity than Eridano. Differences were also observed in guaiacol peroxidase activities between control and acclimated seedlings: Higher guaiacol peroxidase activities were found in the leaves of 12/5°C‐grown seedlings while in roots these activities were lower. Moreover, Brasilia guaiacol peroxidase activities were higher than Eridano. Superoxide dismutase and peroxidase zymogram analyses showed that synthesis of new isoforms was not induced by low‐temperature treatment.Changes in the activities of antioxidant enzymes induced by cold acclimation support the hypothesis that a frost‐resistant wheat cultivar, in comparison with a less frost‐resistant one, maintains a better defence against activated oxygen species during low‐temperature treatment.
Current antiviral strategies for controlling cytomegalovirus in hematopoietic stem cell transplant recipients: prevention and therapy
Authors: Boeckh M. 
Published: March 2003

Abstract:Cytomegalovirus (CMV) remains a cause of significant morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Ganciclovir prophylaxis, or preemptive treatment based on detection of antigenemia or CMV DNA by PCR, effectively prevents CMV disease during the first 100 days after transplant in allograft recipients. In recipients of T‐cell depleted transplant or if severe acute graft‐versus‐host disease is present, ganciclovir prophylaxis or preemptive treatment should be started with an induction course of ganciclovir (5 mg/kg BID) and given at least 5 days per week and continued until day 100 after transplant. Although prevention of CMV disease before day 100 is highly effective, there is a continued risk of late‐onset CMV disease after day 100. In CMV‐seropositive recipients, the incidence of late CMV disease may be as high as 17%. Strategies to prevent late CMV infection and disease are needed. In seronegative recipients, seronegative or leukocyte‐reduced blood products are effective in preventing acquisition of CMV through blood products. Controversy exists about the optimal strategy of preventing CMV disease in seropositive autologous HSCT recipients. The outcome of CMV pneumonia remains poor despite treatment with ganciclovir in combination with CMV hyperimmune globulin or intravenous immunoglobulin. Owing to continued clinical significance of CMV in the HSCT setting, new and more effective anti‐CMV drugs with improved pharmacokinetic properties are urgently needed.
Heterotopic cardiac xenotransplantation: fish‐to‐rat
Authors: Yu Weiming , Wright Jr James R. 
Published: March 2003

AbstractThe purpose of this study was to determine whether a vascularized organ transplanted from a teleost fish to a rodent would be hyperacutely rejected. Previous reports describing the results of discordant xenotransplantation are almost exclusively across orders within the class Mammalia. We chose a species combination that crosses many phylogenetic barriers (i.e. species, genus, family, order, and class) as well as several hundred million years on an evolutionary timescale. Because no published methodology existed, we developed a microvascular surgical method for fish (tilapia)‐to‐rat heterotopic cardiac xenotransplantation. To minimize the blood pressure to which the graft would be exposed, the tilapia heart was placed on the venous side of the rat circulation between the left kidney and the inferior vena cava by end‐to‐side anastomoses of the donor aorta to the recipient inferior vena cava and by end‐to‐end anastomosis of the donor sinus venosus to the recipient left renal vein. Tilapia hearts were rejected hyperacutely, based on both routine histopathological examination and immunofluorescent staining for immunoglobulin and complement, but rejection required hours rather than minutes.
The target antigens of naturally occurring human anti‐β‐galactose IgG are cryptic on porcine aortic endothelial cells
Authors: Lucq Julia , Tixier Denis , Guinault Anne Marie , Greffard Anne , Loisance Daniel , Pilatte Yannick 
Published: March 2003

Abstract: The identification of the xeno‐antigens/xeno‐antibodies combinations involved in pig‐to‐human xenograft rejection is an essential step for understanding this process and for the development of procedures to prevent it. Although it is widely accepted that the terminal disaccharide Galα1,3Gal‐R is by far the major epitope recognized by human natural antibodies reactive with pig tissues, there is also evidence that other carbohydrates epitopes might be important in xenograft rejection.In an attempt to further improve our knowledge of the repertoire of human natural antibodies with anti‐pig specificity we sought to determine whether naturally occurring human anti‐β‐galactose IgG could interact with porcine aortic endothelial cells (PAEC). Histochemical analysis of porcine aorta sections revealed that the carbohydrate structures recognized by the anti‐β‐galalactose IgG are present on endothelial cells but in a cryptic form that can be unmasked by sialidase treatment. These structures were also found to be cryptic in cultured PAEC. In addition we demonstrated that PAEC may adsorb fetal calf serum (FCS) glycoproteins when cultured in FCS‐supplemented medium, a process susceptible to generating artifactual observations in carbohydrate antigens analysis.In conclusion, despite their abundance, human anti‐β‐galactose IgG do not represent a primary concern in pig‐to‐human xenotransplantation as the carbohydrate structures to which they bind are normally masked by sialic acid residues on porcine endothelial cells. However, whether these cryptic epitopes might be exposed on endothelial cells from genetically engineered animals should be further investigated because, if so, additional approaches will be needed to suppress their interaction with human anti‐β‐galactose IgG.
Comparative study of efficacy of removal of anti‐ABO and anti‐gal antibodies by double filtration plasmapheresis
Authors: Kobayashi Takaaki , Yokoyama Itsuo , Morozumi Kunio , Nagasaka Takaharu , Hayashi Shuji , Uchida Kazuharu , Takagi Hiroshi , Nakao Akimasa 
Published: March 2003

Abstract: Successful clinical ABO‐incompatible renal transplantation has been achieved by the removal of anti‐A or anti‐B antibodies using double filtration plasmapheresis (DFPP). We have compared changes in the levels of anti‐donor antibodies and the histopathology of the renal grafts following human ABO‐incompatible allotransplantation and pig‐to‐baboon xenotransplantation using pretransplantDFPP.DFPP was performed on days −6, −4, −2 and −1 before the ABO‐incompatible transplants (n = 25) and on days −2 and 0 (immediately before reperfusion) in the xenotransplants (n = 4). In two baboons (XenoTx Group I) the extent of antibody removal was comparable to that in the ABO‐incompatible patients, and an even greater level of removal was achieved in another two baboons (XenoTx Group II). Anti‐A and anti‐B and anti‐pig IgM and IgG antibodies were measured by flow cytometry.All clinical ABO‐incompatible renal grafts are functioning, except two which were lost from recurrence of the original disease or from chronic rejection. Three other grafts underwent humoral rejection episodes, which were successfully treated. DFPP reduced the mean anti‐A/B IgM and IgG antibody levels to 8% and 13% of pre‐treatment levels, respectively. After kidney transplantation, they were maintained at 37% and 46% of pre‐DFPP level. No antibody binding to the transplanted kidney was detected at any time (1 h to 2 yr) after ABO‐incompatible allotransplantation. In contrast, in XenoTx Group I, the same extent of antibody removal (90%) prevented hyperacute rejection, but the two grafts were rejected on days 6 and 7, respectively, from acute vascular rejection. In XenoTx Group II, the additional DFPP that was required to deplete the remaining 10% of anti‐pig antibody was poorly tolerated and the two baboons died 4 h and 2 days, respectively, after renal transplantation. Although anti‐pig IgM antibodies were reduced to 2% of pre‐treatment level, IgM and C3 binding were detected in the graft as early as 1 h post‐transplantation.These data suggest that the concentration of xeno‐antigen epitopes expressed on pig organs may need to be reduced by genetic engineering to the much lower level of blood group A/B antigens on human kidneys if discordant xenotransplantation is to besuccessful.
A longitudinal evaluation of pulpal pain during orthodontic tooth movement
Authors: Leavitt AH , King GJ , Ramsay DS , Jackson DL 
Published: March 2003

Abstract Objectives – To examine the longitudinal changes in pulpal sensitivity to electrical stimulation and the relationship to pulpal sensitivity as measured by electrical stimulation and subjective reports of tooth pain after archwire insertion. Design – Non‐randomized, prospective trial, with matched controls. Setting and Sample Population – Regional Clinical Dental Research Center at the University of Washington School of Dentistry. Eighteen adult subjects of age 13–37 years. Nine experimental subjects planned for orthodontic treatment. Nine control subjects matched for gender and age who did not have orthodontic treatment. Experimental Variable – Fixed orthodontic appliances and initial archwire placement in experimental subjects compared with `no treatment' control subjects. Outcome Measure – Subjective assessments of orthodontic tooth pain were made using visual analogue scales. Electrically evoked detection and pain thresholds were determined using a computer‐controlled tooth stimulator. Data were gathered at five time points: after bracket placement (baseline), 1 h after placement of initial archwires, 1 day after archwire placement, 1 week after archwire placement, and 1 month after archwire placement. Comparable time intervals were used for the `no treatment' control subjects. Results – Subjective ratings of treatment‐evoked tooth pain in the experimental group were the greatest at the post‐archwire day 1 observation and progressively decreased for the remaining observations. Control subjects reported little pain at any of these observation times. The detection and pain threshold changes from baseline showed no statistical differences over time or between groups. While not statistically significant, a trend was noted where reports of greater orthodontic tooth pain were associated with increased sensitivity to electrical stimulation (i.e. lower detection and pain thresholds). Conclusion – Orthodontic patients experience significant pain and discomfort 1 day after initial archwire placement (i.e. activation). Future research should investigate whether self‐reports of treatment‐evoked tooth pain intensity are associated with pulpal sensitivity.
Regional size differences in four commonly used cephalometric atlases: the Ann Arbor, Cleveland (Bolton), London (UK), and Philadelphia atlases compared
Authors: Dibbets JMH , Nolte K 
Published: March 2003

Abstract Authors– Dibbets JMH, Nolte K Objective– To explore regional influence on size in roentgenocephalometric atlases. Design– Comparisons of the size of 10 linear distances in four atlases from geographically different regions, i.e. Ann Arbor Michigan, Cleveland Ohio, Philadelphia Pennsylvania and London, UK. Distances compared– anterior cranial base length (S–N), posterior cranial base length (S–Ba), total face height (N–Me), upper face height (N–ANS), lower face height (ANS–Me), mandibular diagonal (Ar–Gn), corpus length (Go–Pg), ramus height (Ar–Go), maxillary length (SNP–SNA), posterior face height (S–Go). Results– Correction for enlargement appeared to be a necessity before distances could be compared. After correction for enlargement, the anterior cranial base was longest in Ann Arbor, lower face height smallest in Cleveland (Bolton standards) and the maxilla was shortest in Philadelphia. Conclusion– Regional size variance in cephalometric data cannot be ignored.