bluuebunny/crossref_metadata_2025 huggingface dataset:
A critical review of daily sedation interruption in the intensive care unit
Authors: O’Connor Mark , Bucknall Tracey , Manias Elizabeth
Published: December 2008

Background. Daily sedation interruption (DSI) has been proposed as a method of improving sedation management of critically ill patients by reducing the adverse effects of continuous sedation infusions.

Aim. To critique the research regarding daily sedation interruption, to inform education, research and practice in this area of intensive care practice.

Design. Literature review.

Method. Medline, CINAHL and Web of Science were searched for relevant key terms. Eight research‐based studies, published in the English language between 1995–December 2006 and three conference abstracts were retrieved.

Results. Of the eight articles and three conference abstracts reviewed, five originated from one intensive care unit (ICU) in the USA. The research indicates that DSI reduces ventilation time, length of stay in ICU, complications of critical illness, incidence of post‐traumatic stress disorder and is reportedly used by 15–62% of ICU clinicians in Australia, Europe, USA and Canada.

Conclusions. DSI improves patients’ physiological and psychological outcomes when compared with routine sedation management. However, research relating to these findings has methodological limitations, such as the use of homogenous samples, single‐centre trials and retrospective design, thus limiting their generalisability.

Relevance to clinical practice. DSI may provide clinicians with a simple, cost‐effective method of reducing some adverse effects of sedation on ICU patients. However, the evidence supporting DSI is limited and cannot be generalised to heterogeneous ICU populations internationally. More robust research is required to assess the potential impact of DSI on the physical and mental health of ICU survivors.
Lecturers’ and students’ perceptions of portfolios in an English School of Nursing
Authors: Williams Glenn A , Park Jennifer R , Traynor Victoria , Nairn Stuart , O’Brien Elisabeth , Chapple Mary , Johnson Stacy
Published: December 2008

Aims.  This study was aimed at comparing perceptions of portfolios between student nurses at the early and latter stages of their training and how they compare with their lecturers’ perceptions.

Background.  Portfolios are used widely in nurse education. There has been research into how portfolios are perceived and understood, but there is little evidence into how student nurses and lecturers compare quantitatively in perceptions of portfolio use.

Design.  Survey.

Method.  Forty‐eight nursing lecturers and 413 nursing students, from a multi‐centred School of Nursing in the UK, completed a questionnaire. Data were analysed with exploratory factor analysis, varimax rotation of the factor solution, internal consistency analysis, and analysis of variance.

Results.  Five factors were extracted, which were labelled: (1) portfolios as a means of skills acquisition, (2) other means of teaching and learning beyond using portfolios, (3) processes of showing the portfolio to others, (4) having favourable attitudes towards portfolios and (5) lecturers’ ability to share knowledge about portfolios. Scales developed from these five factors had high levels of internal consistency. Lecturers were the most positive of the three respondent groups in their views of portfolios, whereas third‐ and fourth‐year students were the least positive. There were significant differences between student nurses and their lecturers, concerning how information on portfolios is communicated by the lecturer.

Conclusion.  There were significant discrepancies between lecturers and student nurses in their views on how portfolios are used. The value of portfolios becomes less salient to student nurses towards the end of their training.

Relevance to clinical practice.  Lecturers and clinical mentors need to look at students’ perceptions and why some nursing students’ views on portfolios deteriorate. There could be regular discussions with students to see how and why the students begin to see portfolios as less useful for their education and continual professional development.
Incidence and risk factors for pressure ulcers in the intensive care unit
Authors: Nijs Nele , Toppets Adinda , Defloor Tom , Bernaerts Kris , Milisen Koen , Van Den Berghe Greet
Published: December 2008

Aims.  To determine the incidence of pressure ulcers occurring at least 48 hours after admission and risk factors for pressure ulcers grade 2–4 in a long‐stay surgical Intensive Care Unit (ICU) population.

Background.  The incidence of pressure ulcers in intensive care units is larger than in non‐intensive environments.

Design.  Prospective descriptive research design.

Methods.  Using pressure ulcers grade 2–4 as an outcome measure, a multivariate logistic regression analysis was used to identify the risk factors. Data were obtained on a daily basis in a surgical intensive care unit of the University Hospital Leuven between November 2003–March 2004. A total of 520 long‐stay (≥ 24 hours) intensive care patients were included.

Results.  Cumulative incidence of pressure ulcers grade 2–4 was 20·1%. The following variables were positively associated with pressure ulcers grade 2–4: history of vascular disease, treatment with Dopamine® or Dobutamine®, intermittent haemodialysis (IHD) or continuous veno‐venous haemofiltration (CVVH), mechanical ventilation. Also preventive measures were statistically positively associated with pressure ulcers grade 2–4: turning, floating heels, alternating mattresses, adequate prevention. The use of sedatives, body temperature above 38·5 °C and sitting in chair where negatively associated with pressure ulcers. Pressure ulcers are statistically associated with different risk factors and preventive measures.

Conclusion.  The identified risk factors are eligible to be included in a new risk assessment scale for patients admitted to intensive care units.

Relevance to clinical practice.  The novel insights have implications for risk assessment for patients in intensive care units. Patients admitted to intensive care units have other risk factors for pressure ulcers which are eligible to be included in a new risk assessment scale.
A developmental approach to the treatment of bipolar disorder: IPSRT with an adolescent
Authors: Crowe Marie , Inder Maree , Joyce Peter , Moor Stephanie , Carter Janet , Luty Sue
Published: December 2008

Aim.  This case study explains how a psychotherapy previously used with adults can be used with adolescents by focusing on the specific developmental issues associated with adolescence.

Background.  Bipolar disorder is a damaging disorder to experience during the developmental phase of adolescence. Interpersonal social rhythm psychotherapy has been developed as an adjunct to medication for managing bipolar disorder and shows some promising outcomes in adults.

Design.  This is a single case study design drawn from a larger randomised control trial of two psychotherapies for bipolar disorder. The case study addressed the question: How can Interpersonal social rhythm therapy be applied with adolescents who have bipolar disorder?

Method.  This study used a purposeful sampling process by selecting the youngest adolescent participating in the randomised control trial. All the subject’s sessions of Interpersonal social rhythm therapy were taped, transcribed and analysed. The analysis involved describing the process of psychotherapy as it occurred over time, mapping the process as a trajectory across the three phases of psychotherapy experience and focusing the analysis around the impact of bipolar disorder and IPSRT on adolescent developmental issues, specifically the issue of identity development.

Results.  Interpersonal social rhythm therapy allowed the therapist to address developmental issues within its framework. As a result of participation in the psychotherapy the adolescent was able to manage her mood symptoms and develop a sense of identity that was age‐appropriate.

Conclusion.  Interpersonal social rhythm therapy provided the adolescent in the case study the opportunity to consider what it meant to have bipolar disorder and to integrate this meaning into her sense of self.

Relevance to clinical practice.  Bipolar disorder is a chronic and recurring disorder that can have a serious impact on development and functioning. Interpersonal social rhythm therapy provides an approach to nursing care that enables adolescents to improve social functioning.
Evidence‐based nursing: clarifying the concepts for nurses in practice
Authors: Scott Kay , McSherry Rob
Published: December 2008

Aim.  To provide a critical analysis of key concepts associated with evidence‐based nursing (EBN) to substantiate an operational definition for nurses to use in practice.

Background.  Despite the plethora of literature surrounding what evidence‐based nursing is and is not and how it differs from its cousins, evidence‐based medicine and evidence‐based practice, nurses still struggle to get evidence into practice. Several reasons for this have been reported, for example, a lack of understanding about what evidence‐based nursing means or time to engage with and apply the evidence into practice.

Design.  An in‐depth critical review and synthesis of literature was undertaken.

Method.  Using the key words; evidence‐based nursing, evidence‐based medicine and evidence‐based practice 496 articles were yielded. These articles were limited to 83. Using Burns and Grove’s (2001) phased approach to reviewing the literature the articles were critically reviewed and categorised into key concepts and themes.

Results.  The in‐depth critical review and synthesis of the literature demonstrated that evidence‐based nursing could be defined as a distinct concept. The review clearly shows that for evidence‐based nursing to occur, nurses need to be aware of what evidence‐based nursing means, what constitutes evidence, how evidence‐based nursing differs from evidence‐based medicine and evidence‐based practice and what the process is to engage with and apply the evidence.

Conclusion.  The in‐depth critical review and synthesis of the evidence‐based nursing literature reinforces the need to consolidate a position for nursing in the evidence‐based field. The review confirms that evidence‐based nursing can be defined and conceptualised; however, for nurses to engage and apply with the evidence‐based processes they need to be informed of what these are and how to engage with them in practice.

Relevance to clinical practice.  This paper examines the concept of evidence‐based nursing and its application to clinical practice.
A role for plant microtubules in the formation of transmission‐specific inclusion bodies of Cauliflower mosaic virus
Authors: Martinière Alexandre , Gargani Daniel , Uzest Marilyne , Lautredou Nicole , Blanc Stéphane , Drucker Martin
Published: December 2008

Interactions between microtubules and viruses play important roles in viral infection. The best‐characterized examples involve transport of animal viruses by microtubules to the nucleus or other intracellular destinations. In plant viruses, most work to date has focused on interaction between viral movement proteins and the cytoskeleton, which is thought to be involved in viral cell‐to‐cell spread. We show here, in Cauliflower mosaic virus (CaMV)‐infected plant cells, that viral electron‐lucent inclusion bodies (ELIBs), whose only known function is vector transmission, require intact microtubules for their efficient formation. The kinetics of the formation of CaMV‐related inclusion bodies in transfected protoplasts showed that ELIBs represent newly emerging structures, appearing at late stages of the intracellular viral life cycle. Viral proteins P2 and P3 are first produced in multiple electron‐dense inclusion bodies, and are later specifically exported to transiently co‐localize with microtubules, before concentrating in a single, massive ELIB in each infected cell. Treatments with cytoskeleton‐affecting drugs suggested that P2 and P3 might be actively transported on microtubules, by as yet unknown motors. In addition to providing information on the intracellular life cycle of CaMV, our results show that specific interactions between host cell and virus may be dedicated to a later role in vector transmission. More generally, they indicate a new unexpected function for plant cell microtubules in the virus life cycle, demonstrating that microtubules act not only on immediate intracellular or intra‐host phenomena, but also on processes ultimately controlling inter‐host transmission.
Surviving floods: leaf gas films improve O2 and CO2 exchange, root aeration, and growth of completely submerged rice
Authors: Pedersen Ole , Rich Sarah Meghan , Colmer Timothy David
Published: December 2008

When completely submerged, the leaves of some species retain a surface gas film. Leaf gas films on submerged plants have recently been termed ‘plant plastrons’, analogous with the plastrons of aquatic insects. In aquatic insects, surface gas layers (i.e. plastrons) enlarge the gas–water interface to promote O2 uptake when under water; however, the function of leaf gas films has rarely been considered. The present study demonstrates that gas films on leaves of completely submerged rice facilitate entry of O2 from floodwaters when in darkness and CO2 entry when in light. O2 microprofiles showed that the improved gas exchange was not caused by differences in diffusive boundary layers adjacent to submerged leaves with or without gas films; instead, reduced resistance to gas exchange was probably due to the enlarged water–gas interface (cf. aquatic insects). When gas films were removed artificially, underwater net photosynthesis declined to only 20% of the rate with gas films present, such that, after 7 days of complete submergence, tissue sugar levels declined, and both shoot and root growth were reduced. Internal aeration of roots in anoxic medium, when shoots were in aerobic floodwater in darkness or when in light, was improved considerably when leaf gas films were present. Thus, leaf gas films contribute to the submergence tolerance of rice, in addition to those traits already recognized, such as the shoot‐elongation response, aerenchyma and metabolic adjustments to O2 deficiency and oxidative stress.
Feasibility of satellite image‐based sampling for a health survey among urban townships of Lusaka, Zambia
Authors: Lowther Sara A. , Curriero Frank C. , Shields Timothy , Ahmed Saifuddin , Monze Mwaka , Moss William J.
Published: December 2008

Objectives  To describe our experience using satellite image‐based sampling to conduct a health survey of children in an urban area of Lusaka, Zambia, as an approach to sampling when the population is poorly characterized by existing census data or maps.

Methods  Using a publicly available Quickbird™ image of several townships, we created digital records of structures within the residential urban study area using ArcGIS 9.2. Boundaries were drawn to create geographic subdivisions based on natural and man‐made barriers (e.g. roads). Survey teams of biomedical research students and local community health workers followed a standard protocol to enrol children within the selected structure, or to move to the neighbouring structure if the selected structure was ineligible or refused enrolment. Spatial clustering was assessed using the K‐difference function.

Results  Digital records of 16 105 structures within the study area were created. Of the 750 randomly selected structures, six (1%) were not found by the survey teams. A total of 1247 structures were assessed for eligibility, of which 691 eligible households were enroled. The majority of enroled households were the initially selected structures (51%) or the first selected neighbour (42%). Households that refused enrolment tended to cluster more than those which enroled.

Conclusions  Sampling from a satellite image was feasible in this urban African setting. Satellite images may be useful for public health surveillance in populations with inaccurate census data or maps and allow for spatial analyses such as identification of clustering among refusing households.
Targeting the MHC class II pathway of antigen presentation enhances immunogenicity and safety of allergen immunotherapy
Authors: Martínez‐Gómez J. M. , Johansen P. , Rose H. , Steiner M. , Senti G. , Rhyner C. , Crameri R. , Kündig T. M.
Published: December 2008

Background:  Current s.c. allergen‐specific immunotherapy (SIT) leads to amelioration of IgE‐mediated allergy, but it requires numerous allergen injections over several years and is frequently associated with severe side‐effects. The aim of this study was to test whether modified recombinant allergens can improve therapeutic efficacy in SIT while reducing allergic side‐effects.

Methods:  The major cat allergen Fel d 1 was fused to a TAT‐derived protein translocation domain and to a truncated invariant chain for targeting the MHC class II pathway (MAT‐Fel d 1). The immunogenicity was evaluated in mice, while potential safety issues were assessed by cellular antigen stimulation test (CAST) using basophils from cat‐dander‐allergic patients.

Results:  MAT‐Fel d 1 enhanced induction of Fel d 1‐specific IgG2a antibody responses as well as the secretion of IFN‐γ and IL‐2 from T cells. Subcutaneous allergen‐specific immunotherapy of mice using the modified Fel d 1 provided stronger protection against anaphylaxis than SIT with unmodified Fel d 1, and MAT‐Fel d 1 caused less degranulation of human basophils than native Fel d 1.

Conclusion:  MAT‐Fel d 1 allergen enhanced protective antibody and Th1 responses in mice, while reducing human basophil degranulation. Immunotherapy using MAT‐Fel d 1 allergen therefore has the potential to enhance SIT efficacy and safety, thus, shortening SIT. This should increase patient compliance and lower treatment costs.
Asthma in Latin America: a public heath challenge and research opportunity
Authors: Cooper P. J. , Rodrigues L. C. , Cruz A. A. , Barreto M. L.
Published: December 2008

Asthma has emerged as an important public health problem in many Latin American countries over the past decade. In Brazil and Costa Rica, the prevalence of asthma and associated morbidity is as great or greater as reported in traditional high prevalence countries such as the US, but remains neglected as a public health priority. Asthma in Latin America is associated particularly with underprivileged populations living in cities but remains relatively rare in many rural populations. The causes of asthma in Latin America are likely to be associated with urbanization, migration, and the adoption of a modern ‘Westernized’ lifestyle and environmental changes that follow these processes that include changes in diet, physical activity, hygiene, and exposures to allergens, irritants, and outdoor and indoor pollutants. Because of the enormous social, genetic, and environmental contrasts within and between Latin American countries, and the large differences in prevalence associated with these differences, the investigation of asthma in Latin America provides important research opportunities to identify the social and biological mechanisms that underlie asthma development. Asthma in Latin America poses enormous challenges for health policy makers, health services, and researchers to respond to and alleviate the growing burden of asthma disability, particularly among marginalized urban populations.
The influence of HLA‐A,B and ‐DR matching and pregraft blood transfusions on graft and patient survival after renal transplantation in a single centre
Authors: Ting Alan , Morris Peter J.
Published: December 2008

The influence of HLA‐A,B and DR matching and pregraft blood transfusions on the graft and patient survival rate of 305 recipients of first cadaver grafts in a single centre has been studied.

All three factors significantly influenced the graft survival rate. The effect of HLA‐A,B matching became apparent only after a follow‐up period of 3 years whereas the effect of HLA‐DR matching was seen within 3 months after transplantation. The survival rate of HLA‐DR compatible grafts was not improved by additional HLA‐A,B matching, but that of HLA‐DR mismatched grafts was improved by HLA‐A,B matching. The HLA‐DR matching effect was seen in both transfused and in non‐transfused patients. However, the highest graft survival rate seen was in the pregraft transfused patients who received a DR compatible kidney (87% at 1 year and 80% at 5 years).

Both HLA‐A,B and DR matching significantly increased the patient survival rate whereas blood transfusion did not. The lower survival rate of patients receiving HLA poorly‐matched grafts was not related to the amount of methylprednisolone received during the first 3 months after transplantation, the age of the patient, or whether the patient was considered medically high risk at the time of transplantation.
Cross reaction of monoclonal antibodies to human MHC class I and class II products with bovine lymphocyte subpopulations
Authors: Spooner R. L. , Ferrone S.
Published: December 2008

Peripheral blood lymphocytes (PBL) from cattle have been separated into T & B cell subpopulations using a panning technique. These T and B cell preparations have then been tested by direct and indirect complement mediated cytotoxicity tests with a series of monoclonal antibodies (Moabs) reacting with HLA class I and class II products.

The anti‐class I monoclonals were monomorphic or non‐reactive and where reactive killed both B and T cells.

The anti‐class II monoclonals reacted only with B lymphocytes. There was no relationship between their reactivity pattern and any BoLA specificity.

This work was supported by the National Institutes of Health Grants AI21384 and CA38469.
Histocompatibility antigens HLA‐A, ‐B, ‐DR in Greek patients with Kaposi's sarcoma
Authors: Papasteriades Chrysa , Kaloterakis A. , Filiotou Anna , Economidou Joanna , Nicolis G. , Trichopoulos D. , Stratigos J.
Published: December 2008

Thirty‐two Greek patients with histologically documented Kaposi's sarcoma, aged 46 to 82 years, were typed for HLA‐A, B and DR antigens. None of them was homosexual and they had not been subjected to any immunosuppressive therapy. The study revealed a significant increase of HLA‐DR5 (53.1% vs. 21.4%, R.R. 4.1) and a decreased frequency of HLA‐DR1 (3.3% vs. 16.6%, R. R. 0.16). An increased frequency of HLA‐B18 was also noted (43.7% vs. 20.7% R.R. 2.96). These results indicate that the same positive association with HLA‐DR5 antigen is observed in Greek patients as in other patients of Mediterranean origin and support the view that HLA linked factor(s) may have a role in the development of the disease.
Predictability of alloreactivity among unrelated individuals
Authors: Awdeh Z. L. , Alper C. A. , Fici D. , Eynon E. , Bishara A. , Yunis E. J.
Published: December 2008

Abstract: Extended haplotypes are specific HLA‐B, BF, C2, C4A, C4B and DR allelic combinations that occur at high frequencies and show positive linkage disequilibrium among these highly polymorphic MHC markers. About 30% of all normal caucasian haplotypes are extended, and the matching of two extended haplotypes in unrelated individuals has been shown to match for the determinants of primary mixed lymphocyte reactivity (MLR‐I). In this work we report that the matching of one extended haplotype and a serologically defined HLA‐DR generic type on the second chromosome in unrelated individuals is associated with the absence of mixed lymphocyte reactivity in 15 to 30% of the cases studied. Our results suggest that, for those individuals who carry either one or two extended haplotypes, it is relatively easy to identify an unrelated MLR‐I‐matched subject. However, for individuals lacking at least one extended haplotype, it should be difficult to find an MLR‐I‐matched unrelated subject.
Rapid HLA‐DRB1 genotyping by nested PCR amplification
Authors: Bein G. , Gläser R. , Kirchner H.
Published: December 2008

Abstract: State of the art genotyping of HLA class II alleles with group‐specific DNA amplification by the polymerase chain reaction (PCR) (1) and subsequent probing with sequence‐specific oligonucleotides (2–4) is not suitable for typing cadaveric organ donors since the typing procedure takes far more than one working day. We designed specific oligonucleotide primer sets for nested PCR amplification which allowed typing for all serological HLA‐DR specificities (DR1‐DRw18) solely by the detection of amplified DNA in the reaction mixtures after agarose gel electrophoresis. Exon 2 of the DRB genes and a DRw52‐group‐specific part of DRB1 exon 2 was amplified directly from cell lysates without prior DNA extraction. The amplified DNA was subjected to a second round of amplification, which employed a set of 18 nested allele‐ or group‐specific primer pairs. All alleles which have at least a single mismatched base at the terminal 3′‐nucleotide of one primer were completely refractory to amplification. This assay is easy to perform and takes less than one working day to complete. Thus, this method may prove to be suitable for DNA typing of organ donors for prospective HLA‐DR matching in renal transplantation.
Soluble HLA class I and class II concentrations in commercial immunoglobuh preparations
Authors: Grosse‐Wilde H. , Blasczyk R. , Westhoff U.
Published: December 2008

Abstract: Soluble HLA class I (sHLA‐ABC) and class II (sHLA‐RQP) molecules were quantitated in 16 commercially available immunoglobulin (Ig) preparations by enzyme‐linked immunosorbent assays. Whereas three Ig preparations contained no detectable sHLA‐ABC, all preparations showed concomitant sHLA‐RQP molecules. There was a considerable variability with regard to the individual sHLA concentrations. For sHLA‐RQP the values exceeded that found in human plasma of healthy individuals, suggesting that the extraction procedure may concentrate not only Ig, but also HLA class II molecules. Based on the total dosage of intravenously administered immunoglobulins (i.v.Ig), contaminating sHLA molecules may become immunogenic. Furthermore, sHLA molecules are discussed in terms of participation in the well‐known immuno‐modulating effects of i.v.Ig therapy.
Studies of the HLA class II alleles involved in human responses to ragweed allergens Ambrosia artemisiifolia V (Ra5S) and Ambrosia trifida V (Ra5G)
Authors: Goldstein Rose , Yang William H. , Drouin Michel A. , Karsh Jacob
Published: December 2008

Abstract: Previous studies have associated skin test sensitivity and specific IgE response to Ambrosia artemisiifolia V (Amb a V) with HLA‐DR2, and to Ambrosia trifida V (Amb t V) with HLA‐DRw52 haplotypes in atopic individuals. Using HLA class II typing by restriction fragment length polymorphism (RFLP) analysis with DRB, DQB and DQA DNA probes to define the HLA‐D alleles, we have demonstrated the association of the DQw6 in 16 out of 16 (100%) Amb a V‐responsive individuals, compared to 3 out of 18 (17%) ragweed‐sensitive but Amb aV‐nonresponsive individuals (p = 5.7 × 10‐6, RR>75). We suggest that the DQw6 association with Amb a V sensitivity may be a reflection of an association with the DQA*0102 allele. This suggests an association of a particular HLA class II allele with an immune response to a well characterized antigen (Amb a V). The HLA‐DRw52 haplotypes in the Amb t V‐sensitive individuals are not of one particular subtype. The HLA‐DRw52 association with Amb t V sensitivity may reside in homologous DRB1 alleles linked on HLA‐DRw52‐bearing haplotypes.
The HLA DQB 1*0502 allele is neutrally associated with insulin‐dependent diabetes mellitus in the Sardinian population
Authors: Muntoni F. , Congia M. , Cucca F. , Cossu P. , Porcu S. , Frau F. , Arnone M. , Songini M. , Muntoni S. , Gao A. , Pirastu M.
Published: December 2008

Abstract: In the Sardinian population a very high incidence of insulin‐dependent diabetes mellitus (IDDM) and the lack of HLA‐DR2 protective effect due to the high‐frequency of the A2, Cw7, B17, 3F31, DR2, DQw1 extended haplotype has been reported. This haplotype, carrying a Serine at position 57 of the DQB 1*0502 allele, has been previously reported to be underrepresented in patients when compared to controls. In order to provide an explanation for this finding, we defined by RFLP analysis the HLA haplotype of 45 Sardinian IDDM patients and 49 controls. All DR‐2DQw1 subjects were molecularly characterized at the HLA DQA and DQB loci. All DR2‐positive patients and the vast majority of the DR2‐positive controls had the DQB 1*0502 allele at the DR2‐linked DQB1 locus, with no statistically significant difference between the two groups. All DQA1 genes were the ones expected, with only two exceptions. Nine out of 10 of the DRZ‐positive patients were compound hetero‐zygotes for DQB 1*0201/DQB1*0502 alleles; only this allele combination was significantly increased (p< 0.0003). Our data suggests that a) the DQB 1*0502 allele is neutral for IDDM development and b) the susceptibility to IDDM in our DR2‐positive patients is related to the compound hetrozygous state between the neutral DQAl*0102/DQB1*0502 and the susceptibility DQA1*0501/DQB1*0201 alleles.
HLA‐DP polymorphism in northern Italian celiac patients
Authors: Mantovani V. , Corazza G. R. , Frisoni M. , Zaniboni M. G. , Bragliani M. , Valentini R. A. , Barboni P. , Lambertini A. , Gasbarrini G.
Published: December 2008

The contribution of HLA‐DP genes to celiac disease susceptibility has been investigated in 95 Italian patients, 41 with childhood and 54 with adult disease onset. Polymerase chain reaction amplification, sequence‐specific oligonucleotide probe hybridization and restriction fragment length polymorphism analyses have been carried out. All celiac patients and 56 out of 128 random healthy controls were DQw2‐positive. The frequency of the DPB1*0101 allele was significantly increased (pc = 0.002, relative risk 5.21) in patients with celiac disease (23.2%) compared to the whole panel of controls (5.5%), but not to the 56 controls bearing DQw2 (10.7%). No significant difference in the frequency of DPB1*0101 was found between celiac patients with pediatric (24.4%) or adult (22.2%) onset. The DPB1*0101 allele was associated with both the DR3‐DQw2 and DR7‐DQw2 haplotypes. Moreover, our study has not confirmed the association with DPB1*0402 and DPB1*0301 previously reported in celiac children from southern Italy. The linkage of the DPB1*0101 allele with the DQ locus and the observation that the DP but not the DQ association appears to be ethnically dependent strongly support a secondary role of DP molecules in celiac diseae susceptibility.
HLA Class I nucleotide sequences, 1992
Authors: Zemmour Jacqueline , Parham Peter
Published: December 2008

The HLA Class I sequences included in this compilation are taken from publications listed in the papers: Nomenclature for factors of the HLA system, 1991 (1), Nomenclature for factors of the HLA system, 1990 (2), and Nomenclature for factors of the HLA system, 1989 (3). Due to the increased number of sequences, we have only included sequences for exons 2, 3 and 4 in this compilation. Where discrepancies have arisen between reported sequences, the original authors have been contacted where possible, and necessary amendments to published sequences have been incorporated into this alignment. Future sequencing may identify errors in this list and we would welcome any evidence that helps to maintain the accuracy of this compilation. In the sequence alignments, identity between nucleotides is indicated by a hyphen (‐). An unavailable sequence is indicated by a period (.). Gaps in the sequence are inserted to maintain the alignment between different alleles showing variation in amino acid number
Expression of HLA class I‐encoded cell surface antigens in transitional cell carcinoma of the urinary bladder
Authors: Levin Israel , Klein Baruch , Segal Shraga , Eyal Arnona , Gopas Jacob , Kaneti Jacob , Saadon M. , Kuperman Oded
Published: December 2008

Abstract: I. Levin, B. Klein, S. Segal, A. Eyal, J. Gopas, J. Kaneti, M. Saadon, O. Kuperman. Expression of HLA class I‐encoded cell surface antigens in transitional cell carcinoma of the urinary bladder.
Strong linkage disequilibrium of HLA DPw11 with the HLA B44‐DR7‐DQw2 extended haplotype*
Authors: Bignon J. D. , Cheneau M. L. , Herry P. , Bonneville F. , Cesbron A. , Muller J. Y.
Published: December 2008

Abstract: J. D. Bignon, M. L. Cheneau, P. Herry, F. Bonneville, A. Cesbron, J. Y. Muller. Strong linkage disequilibrium of HLA DPw11 with the HLA B44‐DR7‐DQw2 extended haplotype. Tissue Antigens 1992: 39: 35‐37.
HLA‐DPB1 alleles correlate with risk for multiple sclerosis in Caucasoid and Cantonese patients lacking the high‐risk DQB1*0602 allele
Authors: Dekker J. W. , Eastsal S. , Jakobson I. B. , Gao X. , Strwart G. J. , Buhler M. M. , Hawkins B. R. , Higgins D. A. , Yu Y. L. , Serjeantson S. W.
Published: December 2008

Multiple Sclerosis (MS) is a demyelinating disease associated with the HLA‐DR2‐related haplotype DRB1*1501, DQB1*0602 in Caucasoids and with DQB1*0602 in DR2‐positive Cantonese. However, many MS patients do not have the high‐risk HLA‐D determinants and alternative genes may contribute to the pathogenesis of MS. One candidate gene is HLA‐DPB1. Our reanalysis of five earlier reports of HLA‐DPB1 antigen distributions in Caucasoid MS patients shows a consistent and highly significant increase (p = 1.5 × 10‐5) in frequency of HLA‐DPw3 in the combined data set. This study tests whether HLA‐DPw3 (DPB1*0301) is also increased in frequency in Australian and Cantonese MS patients and whether any distortion in DPB1 allelic distributions can be attributed to linkage disequilibrium with DQB1*0602. PCR‐RFLPs were used to determine distributions of 20 HLA‐DPB1 alleles in 41 Australian MS patients and 67 controls of known DQB1*0602 status and in 11 Cantonese MS patients and 33 controls positive for HLA‐DR2. HLA‐DP distributions in Australian MS patients and controls positive for DQB1*0602 did not differ, but in those MS patients lacking DQB1*0602, the DPB1*0301 antigen (phenotype) frequency was significantly (p = 0.006) increased (50.0%) when compared with DQB1*0602‐negative controls (9.1%). DPB1*0301 was associated (p = 0.003) with DQB1*0402 (DR8) in Caucasoid MS patients. In Cantonese MS patients positive for DQB1*0602, there was an increase in frequency of DPB1*0201 (66.7%) compared with HLA‐DR2‐positive controls negative for DQB1*0602 (10.0%), possibly due to linkage disequilibrium (p = 0.06) with the DRB1*1501, DQB1*0602 haplotype. In DR2‐positive Cantonese lacking DQB1*0602, DPB1*1301 was increased in MS patients (80%) when compared with controls (13.3%) although the association did not reach statistical significance when the p value was corrected for multiple comparisons; the increase could not be accounted for by linkage disequilibrium with any HLA‐DR2‐related haplotypes. This study suggests that the HLA‐DPB1 locus, or a closely‐linked locus, may contribute to inherited susceptibility for MS in those lacking high‐risk HLA‐DR,DQ region determinants.
HLA‐DQA1, DQB1 and DPB1 alleles on HLA‐DQ2‐ and DQ9‐carrying extended haplotypes
Authors: Yunis Juan J. , Salazar Marcala , Delgado Maria B. , Alper Chaster A. , Bing David H. , Yunis Edmond J.
Published: December 2008

DQA1, DQB1 and DPB1 alleles were investigated in a large panel of samples carrying HLA‐DQ2‐ and HLA‐DQ9‐bearing extended haplotypes. Every instance of the [HLA‐B8, SCO1, DR3, DQ2a] and [HLA‐B18, F1C3, DR3, DQ2b] extended haplotypes carried the DQA1*‐0501 allele, while every instance of [HLA‐844, F1C31, DR7, DQ2c], (HLA‐B47, FC91,0, DR7, DQ2c] and [HLA‐B57, SC61, DR7, DQ2d] carried the DQA1*0201 allele. All HLA‐DR3, DQ2 and HLA‐DR7, DQ2 extended haplotypes carried the DQB1*0201 allele. Every example of [HLA‐B57, SC61, DR7, DQ9] carried the DQB1*0303 allele. Several associations between the DPB1 alleles and some HLA‐DQ2‐ and DQ9‐carrying extended haplotypes were identified. HLA‐DPw2‐encoding alleles. DPB1*0202 (50%, p < 0.001) and 0201 (30%). were found on the [HLA‐B18, F1C30, DR3, DQ2b] extended haplotype. Every instance of the [HLA‐B57, SC61, DR7, DQ9] extended haplotype carried the DPB 1*0401 allele. Also, we have confirmed the associations of the DPB1*0101 and DPB1*0401 alleles with the [HLA‐B8, SC01. DR3, DQ2a] extended haplotype. The analysis of hornozygous typing cells carrying the [HLA‐B44. FC31, DR7, DQ2c] extended haplotype showed that the DPB1*0401 and 0201 alleles were present at similar frequencies (37.5%). while the DPB1*1101 allele was found in only 25% of these haplotypes analyzed. Our results suggest that the constancy of the DNA of the HLA‐B, DR, DQ regions may extend to the DP region and that the extent of such fixity varies, perhaps as the result of ethnic variability of the population studied.
Structural diversity in the HLA‐A10 family of alleles: Correlations with serology
Authors: Madrigal J. Alejandro , Hildebrand William H. , Belich Mônica P. , Benjamin Richard J. , Little Ana‐Margaret , Zemmour Jacqueline , Ennis Peter D. , Ward Frances E. , Petzl‐Erler Marla Luiza , du Toit Ernette D. , Parham Peter
Published: December 2008

The HLA‐A10 crossreacting group consists of the A25, A26, A34, A43 and A66 antigens. Here, we report allelic sequences for A43 and for 2 subtypes of both A26 and A34. Combining these results with previously determined sequences for A25, A26 and A66 enables molecular comparison of all the serologically defined A10 antigens. They form a closely related and well‐defined group of alleles which may have originated with A*2601. Patterns of serological crossreactivity are correlated with sequence and a public epitope shared by A33 and members of the A10 family is localized to residues R62 and N63. The A*2501, A*4301 and A*6601 alleles appear to have derived from A*2601 by single gene conversion events with other HLA‐A alleles. In the case of A*4301, the donor allele was probably an A29 allele as A*4301 has a small element of sequence in the α1helix (residues L62 and Q63) uniquely shared with A29. The chimaeric structure of A43 explains the reactivity of A43 molecules with both A10 and A29 alloantisera. The rare Oriental variant of A26 (A26v*) is encoded by an allele (A*2602) that differs from A*2601 by a unique nucleotide substitution which changes aspartate to asparagine at position 116 in the floor of the peptide binding groove. Thus A*2602 is a functionally distinct allele that originated by a point mutation. Alleles encoding A34 and A66 antigens are found to have very similar structures, explaining the difficulty in their serological definition. Further illustration of serological difficulties in discriminating the antigens of the A10 group is the finding that the A26.2 electrophoretic variant of A26 is identical in structure to A*6601.
Serologic and molecular studies of two kindreds expressing recombinant HLA DR1/DR2 haplotypes
Authors: Wisecarver James , Shephed Shirley , Beisel Kirk , Rubocki Ronald
Published: December 2008

We have recently identified two unrelated kindreds in which DR1 and DR2 co‐segregate as a single haplotype spanning several generations. Serology, PCR‐RFLP and sequence‐specific oligonucleotide probes were used to characterize the presence and segregation of the DRB1 and DRB5 loci in these two kindreds. In both families, the recombination resulted in co‐expression of a DRB1 locus that encoded a DR1 serologic phenotype and a DRB5 locus that encoded a “short” DR2 serologic phenotype. One of these kindreds co‐expressed the DR1 and DR15 (DRB5*01). The other kindred co‐expressed the DR1 and DR16 (DRB5*02). Our data indicate that the recombination event occurred in the region between the DRB1 locus and the DRB5 locus. This recombinant haplotype produces a DR2 phenotype which lacks the epitopes normally encoded by the DRB1 locus, resulting in a serologic “short” antigen. The clinical significance of such a recombinational event becomes evident when patients with such a genotype require allogeneic bone marrow transplantation.
HLA matching of unrelated bone marrow transplant pairs: Direct sequencing of in vitro amplified HLA‐DRB1 and ‐DQB1 genes using magnetic beads as solid support
Authors: Spurkland Anne , Knutsen Ingebjrg , Markussen Gunnar , Vartdal Frode , Egeland Torstein , Thorsby Erik
Published: December 2008

Sequencing of HLA genes can offer complete information on the HLA class II genes relevant for the outcome of bone marrow transplantation (BMT). Genomic HLA matching of unrelated BMT patient/donor pairs is often based on PCR‐SSO typing of HLA class II alleles. Typing a small number of samples by this approach is both expensive and time‐consuming, due to the large number of SSO probes required to perform a complete class II typing. Moreover, only polymorphisms explicitly tested for will be found. We now provide the first report of the use of direct sequencing of HLA‐DRB1 and ‐DQB1 genes, using PCR‐amplified genomic DNA attached to magnetic beads, for clinical routine HLA matching. Sequencing ladders obtained by this procedure are easily readable, the patterns can be interpreted in HLA homozygous as well as heterozygous individuals, and sequence differences or similarities between the BMT donor and recipient can be directly identified. This genomic typing method is informative, relatively fast and therefore well‐suited for the small number of samples usually analyzed in matching of BMT pairs. Furthermore, this technique has the potential for automation.
A human monoclonal antibody that detects HLA‐A1, A23 and A24 antigens
Authors: Kubo K. , Tachino J. , Yamaguchi H. , Kurachi T. , Naoe T. , Ohno R. , Ueda K.
Published: December 2008

We report the production and characterization of a human monoclonal IgM (μ, μ) antibody recognizing the HLA A1, A23 and A24 antigens. B lymphocytes obtained from a multiparous Japanese woman were transformed in vitro by Epstein‐Barr virus, screened with an immune adherence assay, and fused with a murine myeloma cell line, P3‐X63‐Ag8.653. After subcloning by limiting dilution three times, a stable antibody‐secreting hybridoma cell line, 4‐35‐7, was identified. The culture supernant had a titer of 1:32‐64 against each of A1‐, A23‐ and A24‐positive lymphocyte panels, and showed complete correlation (r=1.00) with the A1, A23 and A24 antigens on a lymphocyte panel of 287 unrelated, class I HLA‐typed donors by the NIH cytotoxicity assay. Monoclonality of the antibody was ensured by Southern blot analysis of the human immunoglobulin heavy chain gene of 4–35–7. In view of the published data on HLA class I nucleotide sequences, the antibody may recognize an antigeneic determinant including two amino acid residues, Asp‐166 and Gly‐167, in the α2 helix of the class I molecule that are specific for A1, A23 and A24 so far analyzed.
HLA‐DR and ‐DQ genotyping by PCR‐SSO in Shanghai Chinese
Authors: Wang Fu Qing , Semana Gilbert , Fauchst Renée , Genetet Bernard
Published: December 2008

The polymorphism of HLA class II (HLA‐DRBI, ‐DQA1 and ‐DQBI) were investigated in 89 Shanghai Han Chinese using polymerasechain reaction amplification and oligonucleotide (PCR‐SSO) typing. Of the 43 DRB1 alleles tested, 24 were observed. DRBI *0901 (16.85%), *0803 (9.55%), *1202 (9.55%) and *1501 (12.92%) were most frequent and account for the high frequencies of DR9, DR8, DR5 and DR2 specificities in this population. The alleles DRB1 *0101. *0102 and *1001 had very low frequencies. Among the 8 DQA1 and 13 DQB1 alleles tested, only DQA1 *0401 and DQB1 *0402 were absent. DQA1 *0301, and DQB1 *0301 and *0303 were among the most common alleles of the two loci respectively. Unusual DRB1‐DQA1‐DQB1 haplotypes were observed and a DRB1 “new” allele was suggested.
HLA class II DNA typing in two Brazilian populations
Authors: Moraes M. Elisa , Fernandez‐Vińa Marcelo , Salatiel I. , Tsai Shwuyu , Moraes J. Roberto , Stastny Peter
Published: December 2008

Brazil constitutes a melting pot of populations arising from three major groups, including Amerindians, Africans, and Europeans predominantly from Portugal who were later supplemented by migrations from other European countries. Although every possible combination of racial mixture exists in Brazil, we have selected for this study two groups of subjects residing in Rio de Janeiro. A predominant White population, among whom some Amerindian admixture may exist, and a predominantly African population having little admixture from the other races. We have used the polymerase chain reaction (PCR) and hybridization with oligonucleotide probes to perform a complete typing of the HLA class II alleles. We report the allele frequencies for HLA‐DRB1, DQA1, DQB1 and DPB1. We also report on the postulated DR‐DQ haplotypes based on family studies and observations in homozygous B‐cell lines. These results may serve as background for various types of clinical studies in Brazilian populations.
Nucleotide sequences of the variable regions of a human monoclonal antibody against HLA‐A1, A23, and A24
Authors: Ichihashi Takuji , Kubo Kazuaki , Naoe Tomoki , Ohno Ryuzo
Published: December 2008

Nucleotide sequences of the heavy and light chain variable (VH and VL) regions of a human monoclonal antibody (4–35–7), which recognized HLA‐A1, A23 and A24, were determined by means of the reverse transcriptase‐polymerase chain reaction. This antibody was generated by Epstein‐Barr virus transformation of lymphocytes obtained from a multiparous donor, followed by fusion with mouse myeloma cells. The VH gene segment belonged to the VHIII gene Family, and used the DXP4 and JH4 gene segments. This VH gene segment had 92.9% homology to the germline gene VH26, and contained 21 nucleotide substitutions. Fourteen of them generated the replacements of amino acids. while 7 failed to generate the replacement. The ratio of replacement to silent mutations in complementarity determining regions (CDRs) was 7.0. The VL gene segment belonged to the VkI gene family, and used Jk4. This VL gene segment showed 96.1% homology to the germline gene HK102, and contained 11 nucleotide substitutions. Seven of them generated the replacement of amino acids, while 4 failed to generate the replacement. The high ratio of replacement to silent mutations in CDRs of the VH gene segment suggested that the multiparity caused the processes of antigenic selection and somatic mutation, and generated this anti‐HLA antibody.
Multiple sclerosis in the Faroe Islands VI. Studies of HLA markers
Authors: Jersild C. , Kurtzke J. F. , Riisom K. , Heltberg A. , Arbuckle J. , Hyllested K.
Published: December 2008

Abstract: Occurrence of clinical neurologic multiple sclerosis (CNMS) among resident Faroese began between 1943 and 1973 and comprised three epidemics. The occupation by British forces for 5 years during World War II was interpreted to have been of major importance for the Occurrence of these epidemics and led us to believe that CNMS is the rare, late result of a single, widespread, systemic and specific infectious disease which we have labelled the primary MS affection (PMSA). In this study we describe the occurrence of genetic markers of the HLA system in 16 Faroese MS patients, 25 of their siblings, 30 unrelated healthy neighbors and spouses to MS patients, 18 healthy controls from areas where no MS cases have been detected, and 80 unrelated normal Faroese. These studies show no significant deviations of HLA class I antigens, whereas the class II antigens do deviate: 50% of the Faroese MS patients carry the HLA‐DR2 (DQ1/DRB 15) antigen, compared to a frequency of 15–20% among the control groups. Also the group of siblings of MS patients showed an increased frequency of DR4 (72%) compared to normal frequency among MS patients and other normal controls (43–47%). However, if DR15‐positive individuals were excluded, this difference was further reduced. If PMSA was widespread within this group, DR4 or some closely associated genetic marker may confer protection against PMSA developing into CNMS. The occurrence of CNMS in these epidemics seems therefore associated to HLA class II‐linked genetic factors similar to those found in studies of other caucasians with MS. This observation seems important in understanding the pathogenesis of this disease.