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F Christiansen

Publications and source records attributed to F Christiansen.

At least 19 recordsLinked to original sources
PubMed2005

Does a central MHC gene in linkage disequilibrium with HLA-DRB1*0401 affect susceptibility to type 1 diabetes?

Subtypes of HLA-DR4 are associated with susceptibility or protection against type 1 diabetes (T1DM). We addressed whether this reflects linkage disequilibrium with the true susceptibility locus by studying broader MHC haplotypes marked by alleles of HLA-B, IKBL (adjacent to TNFA) and complement C4. The study used a largely Caucasian cohort from Western Australia. HLA-DRB1*0401 and HLA-DRB1*0405 marked susceptibility to T1DM. In Caucasians, DRB1*0401 occurs predominantly in the 44.1 ancestral haplotype (AH; HLA-A2,B44, DRB1*0401,DQB1*0301) and the 62.1AH (HLA-A2,B15(62),DRB1*0401,DQB1*0302). HLA-B15 marked susceptibility and HLA-B44 marked with resistance to T1DM in patients and controls preselected for HLA-DRB1*0401. A gene between TNFA and HLA-B on the 8.1AH (HLA-A1,B8,;DR3,DQ2) modifies the effects of the class II alleles. Here, alleles characteristic of the 62.1AH (C4B3, IKBL+446*T and HLA-A2,B15) were screened in donors preselected for HLA-DRB1*0401. C4B3 was associated with diabetes, consistent with a diabetes gene telomeric of MHC class II. However, increases in carriage of IKBL+446*T and HLA-A2,B15 were marginal, as too few control subjects were available with the diabetogenic alleles. However, with these tools, selection of HLA-DRB1*0401, DQB1*0302 donors who are positive and negative for C4B3 will allow bidirectional mapping of diabetes genes in the central MHC.

Adolescent↗
PubMed2002

High-dimensional interior crisis in the Kuramoto-Sivashinsky equation.

An investigation of interior crisis of high dimensions in an extended spatiotemporal system exemplified by the Kuramoto-Sivashinsky equation is reported. It is shown that unstable periodic orbits and their associated invariant manifolds in the Poincaré hyperplane can effectively characterize the global bifurcation dynamics of high-dimensional systems.

Journal Article↗
PubMed2002

Common HLA-B8-DR3 haplotype in Northern India is different from that found in Europe.

The aim of this study was to determine whether a common diabetic haplotype, including human leukocyte antigen (HLA)-B8 and HLA-DR3, in Northern India is the same haplotype as the European HLA-B8-DR3 haplotype. DNA samples from Northern Indian subjects selected on the basis of HLA-B8 and HLA-DR3 were tested for microsatellite and single nucleotide polymorphism alleles throughout the major histocompatibility complex (MHC). It was found that the Indian samples represent a conserved haplotype in which all alleles were shared by Indian subjects with HLA-B8 and HLA-DR3, but were different to those that are characteristic of the European 8.1 ancestral haplotype. The Indian and European haplotypes share HLA-B*0801, HLA-DRB1*0301 and HLA-DQB1*02 but differ for subtypes of HLA-Cw*07 and HLA-DRB3 and all central MHC alleles tested. In contrast, Indian subjects selected on the basis of HLA-B58 ( 1-17) and HLA-DR3 shared the same alleles at other MHC loci as have been described in the common Chinese haplotype with HLA-B58/17 and HLA-DR3. A third haplotype, HLA-B50/21 and HLA-DR3, was also found to be highly conserved but shares little in common with the other two HLA-DR3-containing Indian haplotypes.

Diabetes Mellitus, Type 1↗
PubMed2001

Variation in behavioural responses of ewes towards predator-related stimuli.

Thirty-two groups of six sheep, classified into three breed categories according to their weight class (L: light, one breed (n=7); M: medium light, two breeds (n=10); H: heavy, three breeds (n=15)) were tested for antipredatory behaviour towards seven stimulus regimes. Tests were performed on 2-5-years-old ewes with lambs inside standardised and fenced home pastures. Stimulus regimes were: man in rain poncho, trolley, ball on trolley (blind stimuli), stuffed wolverine on trolley, stuffed lynx on trolley, stuffed bear on trolley, and man in rain poncho with a dog on leash (carnivore stimuli). The L breed showed the longest recovery time, the longest flight distance and the tightest flocking behaviour. Significant regressions indicate that there were negative linear relationships between sheep weight and recovery time and between sheep weight and flight distance. Carnivore stimuli caused longer recovery times (P<0.001) and longer flight distances (P<0.001) than the blind stimuli. Our results confirm the hypothesis that lighter sheep breeds display stronger antipredatory reactions than heavier breeds.

Journal Article↗
PubMed2001

HLA-DRB1 DNA sequencing based typing: an approach suitable for high throughput typing including unrelated bone marrow registry donors.

The HLA-DRB1 sequencing based typing strategies reported to date require separate amplifications of each sample with a series of group-specific primers followed by sequencing of any resulting polymerase chain reaction (PCR) products. Whilst this results in high resolution typing in the majority of cases, a number of unnecessary amplifications are performed. We report here a novel approach where amplification of the second exon of HLA-DRB1 is performed in a single tube for all alleles. Retrospective analysis of 642 consecutive Western Australian unrelated bone marrow registry donors has shown that this approach results in unambiguous typings in 71.1% of cases. Ambiguities can be readily resolved if necessary with a single additional sequencing reaction on the original PCR product.

Alleles↗
PubMed2000

Unrelated donors selected prospectively by block-matching have superior bone marrow transplant outcome.

Previous retrospective studies have demonstrated improved outcome in patients whose donors were matched for non-HLA markers in the MHC as well as for HLA genes. Forty patients receiving transplants from unrelated donors were typed prospectively for HLA and non-HLA markers. Non-HLA markers near HLA-B (beta-block markers) and in the DRB1 introns (delta-block markers) were used to assess MHC match between donors and recipient. Patients whose donors were matched at the beta- and delta-blocks had improved event free survival (63%) compared to patients whose donors were mismatched at one or both blocks (25%) (p < 0.05). Patients whose donors were matched at the beta-block had significantly less severe acute graft versus host disease (p < 0.05). In order to investigate the basis for improved outcome block matching was correlated with HLA matching as determined by DNA sequencing. Beta-block matching was highly correlated with matching for exons 2 and 3 of HLA-B but less so for HLA-C. Delta-block matching was highly correlated with matching for exon 2 of HLA DRB1. It is concluded that matching for non-HLA markers in the MHC improves matching for HLA genes. Further studies are required to determine whether matching for non-HLA markers improves outcome to a greater extent than matching for the HLA genes alone.

Adolescent↗
PubMed1999

[Spiral computed tomography--solution to diagnostic problems in pulmonary embolism?].

Clinical diagnosis of pulmonary embolism is difficult and often dependent on radiological methods. In Sweden scintigraphy has hitherto been the method most commonly used, though all too often it leaves the diagnosis in doubt. Spiral computed tomography, performed during continuous infusion of contrast medium, clearly depicts the pulmonaries arteries, emboli appearing as filling defects. The examination takes less than one minute. Although the method has yet to be fully evaluated, it is already available at most Swedish hospitals. Results presented so far suggest that the technique has great potential, and may become the method of choice in the diagnosis of pulmonary embolism.

Contrast Media↗
PubMed1999

A special report: histocompatibility testing guidelines for hematopoietic stem cell transplantation using volunteer donors. Quality Assurance and Donor Registries Working Groups of the World Marrow Donor Association.

The World Marrow Donor Association has formulated guidelines for establishing the extent and quality of histocompatibility testing for unrelated donor registries, umbilical cord blood banks, and transplant centers involved in international exchange of hematopoietic stem cells for allogeneic transplantation. Registry and cord blood bank guidelines suggest that, at a minimum, initial HLA typing should be performed for three HLA loci, HLA-A, -B, and -DR, at low resolution/split antigen level. DNA-based testing methods should be utilized for HLA-DR typing. DNA-based testing for HLA-A and -B should replace serologic testing of new volunteer donors and cord blood units as robust protocols and reagents become available to the laboratories. Transplant center guidelines for typing of patient, family and to confirm the HLA types of potential unrelated donors should include, at the minimum, typing HLA-A, B, and -DR loci using primarily DNA-based testing methods at allele level resolution for DRB1 and low resolution/split antigen level for HLA-A and -B. It is strongly recommended that the typing of a patient and the selected donor be performed using the same set of reagents, methodology, and interpretation criteria with fresh tissue samples to ensure HLA identity. Guidelines for laboratory accreditation, approaches to quality assurance and quality control for HLA testing, and suggestions for the format of the HLA database of donor types are also outlined.

Bone Marrow Transplantation↗
PubMed1999

Matching for TNF microsatellites is strongly associated with matching for other non-HLA MHC sequences in unrelated bone marrow donor-recipient pairs.

The use of unrelated donors for bone marrow transplantation is associated with an increased morbidity and mortality when compared with HLA identical siblings. We have demonstrated previously that matching of unrelated donors and recipients for TNFa microsatellites is correlated with lower CTLp frequencies. Matching of unrelated donors and recipients for other non-HLA sequences in the major histocompatibility complex has been reported to result in less graft-versus-host disease and improved survival. It has been argued that matching for non-HLA sequences in the MHC in addition to the HLA genes themselves results in matching for the entire MHC and is therefore the equivalent of providing an HLA identical sibling donor. In order to test this hypothesis we have examined TNFa microsatellites of unrelated donor recipient pairs in whom matching for HLA loci, non-HLA sequences near HLA B (beta-block markers) and non-HLA sequences near DRB1 (delta-block markers) had been determined. All 17 patients who were matched for HLA and non-HLA markers were also matched for TNF microsatellites. This data supports the idea that matching for HLA genes and non-HLA markers results in matching at all other loci in the MHC.

Bone Marrow Transplantation↗
PubMed1999

A special report: histocompatibility testing guidelines for hematopoietic stem cell transplantation using volunteer donors.

The World Marrow Donor Association has formulated guidelines for establishing the extent and quality of histocompatibility testing for unrelated donor registries, umbilical cord blood banks, and transplant centers involved in international exchange of hematopoietic stem cells for allogeneic transplantation. Registry and cord blood bank guidelines suggest that, at a minimum, initial HLA typing should be performed for three HLA loci, HLA-A, -B, and -DR, at low resolution/split antigen level. DNA-based testing methods should be utilized for HLA-DR typing. DNA-based testing for HLA-A and -B should replace serologic testing of new volunteer donors and cord blood units as robust protocols and reagents become available to the laboratories. Transplant center guidelines for typing of patient, family and to confirm the HLA types of potential unrelated donors should include, at the minimum, typing HLA-A, B, and -DR loci using primarily DNA-based testing methods at allele level resolution for DRB1 and low resolution/ split antigen level for HLA-A and -B. It is strongly recommended that the typing of a patient and the selected donor be performed using the same set of reagents, methodology, and interpretation criteria with fresh tissue samples to ensure HLA identity. Guidelines for laboratory accreditation, approaches to quality assurance and quality control for HLA testing, and suggestions for the format of the HLA database of donor types are also outlined.

Hematopoietic Stem Cell Transplantation↗
PubMed1999

Histocompatibility testing guidelines for hematopoietic stem cell transplantation using volunteer donors: report from The World Marrow Donor Association. Quality Assurance and Donor Registries Working Groups of the World Marrow Donor Association.

The World Marrow Donor Association has formulated guidelines for establishing the extent and quality of histocompatibility testing for unrelated donor registries, umbilical cord blood banks, and transplant centers involved in international exchange of hematopoietic stem cells for allogeneic transplantation. The ability to identify unrelated stem cell donors in one country for patients in another country requires cooperation and standardization in many areas. The adoption of guidelines for histocompatibility testing, such as those summarized in this report, will facilitate these opportunities and rapidly provide accurately typed donors for patients in need.

Adult↗
PubMed1999

The genetic basis for the association of the 8.1 ancestral haplotype (A1, B8, DR3) with multiple immunopathological diseases.

An individual's major histocompatibility complex (MHC) ancestral haplotype (AH) is the clearest single determinant of susceptibility to MHC associated immunopathological disease, as it defines the alleles carried at all loci in the MHC. However, the direct effects of any of the 150-200 genes that constitute the MHC are difficult to determine since recombination only occurs at defined hotspots. This review concerns the 8.1 AH (HLA-A1, C7, B8, C4AQ0, C4B1, DR3, DQ2), which is carried by most Caucasians with HLA-B8. It is associated with accelerated human immunodeficiency virus (HIV) disease, and susceptibility to insulin-dependent diabetes mellitus (IDDM), systemic lupus erythematosus, dermatitis herpetiformis, common variable immunodeficiency and IgA deficiency, myasthenia gravis and several other conditions. We have mapped susceptibility genes for HIV, IDDM and myasthenia gravis to the central MHC between HLA-B and the tumour necrosis factor or complement genes. Here we consider which of the remaining 8.1-associated diseases are more closely associated with HLA-DR3 and/or DQ2. Several candidate genes in the central MHC have the potential to modulate immune or inflammatory responses in an antigen-independent manner, as is seen in studies of cultured cells from healthy carriers of the 8.1 AH. Hence these genes may act as a common co-factor in the diverse immunopathological conditions associated with the 8.1 AH.

Animals↗
PubMed1997

Rater agreement at lung scintigraphy after consensus training.

PURPOSE: Using the PIOPED criteria in the interpretation of lung scintigraphy, perfect agreement between experienced raters with training in consensus interpretation has been demonstrated. In a previous paper we found a kappa value of 0.54 (0.45-0.63) between experienced raters with no experience of interpretation in consensus; this is significantly lower than the perfect agreement described between consensus-trained raters. The purpose of this study was to reinvestigate the same study population with the same raters, but this time after they had undergone consensus training. MATERIAL AND METHODS: Lung scintigrams of 192 patients were reviewed and categorized according to the PIOPED criteria by 2 raters after consensus training. The 2 raters reviewed a training material of 59 cases, which was not part of the study population, in order to reach a full consensus interpretation. RESULTS: After consensus training the kappa value was 0.57 (0.48-0.66). Three cases had a discrepancy of 2 categories (1.6%), and the remaining discrepancies were of one category. CONCLUSION: Consensus training did not significantly improve the agreement rate between experienced raters from different hospitals. A substantial improvement in agreement rates between hospitals may make heavy demands on resources.

Humans↗
PubMed1997

Adding a visual linear scale probability to the PIOPED probability of pulmonary embolism.

PURPOSE: Reporting a lung scintigraphy diagnosis as a PIOPED categorical probability of pulmonary embolism offers the clinician a wide range of interpretation. Therefore the purpose of this study was to analyze the impact on lung scintigraphy reporting of adding a visual linear scale (VLS) probability assessment to the ordinary PIOPED categorical probability. MATERIAL AND METHODS: The study material was a re-evaluation of lung scintigrams from a prospective study of 170 patients. All patients had been examined by lung scintigraphy and pulmonary angiography. The scintigrams were re-evaluated by 3 raters, and the probability of pulmonary embolism was estimated by the PIOPED categorization and by a VLS probability. The test was repeated after 6 months. RESULTS: There was no significant difference (p > 0.05) in the area under the ROC curve between the PIOPED categorization and the VLS for any of the 3 raters. Analysis of agreement among raters and for repeatability demonstrated low agreement in the mid-range of probabilities. CONCLUSION: A VLS probability estimate did not significantly improve the overall accuracy of the diagnosis compared to the categorical PIOPED probability assessment alone. From the data of our present study we cannot recommend the addition of a VLS score to the PIOPED categorization.

Angiography↗
PubMed1997

Observer agreement and accuracy for lung scintigraphy: a comparison with pulmonary angiography.

This study investigated whether the moderate observer agreement rate for lung scintigraphy, when using the PIOPED criteria, reflects significant variations in accuracy. In a prospective study, 170 patients were investigated with lung scintigraphy and pulmonary angiography. The lung scintigrams were read according to the PIOPED criteria by three skilled observers from different hospitals who had no experience of consensus interpretation. The scintigrams were reinterpreted 6 months later. The inter-observer agreement rates were moderate and fair, with kappa values of 0.49 (0.44-0.54) for the first reading and 0.36 (0.31-0.41) for the second reading. The intra-observer agreement rates were good and moderate, with kappa values of 0.62 (0.51-0.73), 0.52 (0.42-0.62) and 0.54 (0.44-0.64). There were no significant differences between the observers in the areas under the ROC curves. However, one observer showed a significant difference between his first and second reading (P = 0.02). All three observers showed good accuracy. Although there were substantial variations in the inter- and intra-observer agreement rates, this was only reflected to a minor degree in the accuracy.

Angiography↗
PubMed1997

Diagnostic imaging of acute pulmonary embolism.

The common strategy of combining clinical information, lung scintigraphy and pulmonary angiography in the diagnosis of acute pulmonary embolism (PE), has many limitations in clinical use. The major causes are that pulmonary angiography and lung scintigraphy are not universally available, and that pulmonary angiography is very expensive. The purpose of this thesis was to analyse different aspects of validity in regard to lung scintigraphy, pulmonary angiography, spiral CT, and ultrasound of the legs, with the subsequent intention of discussing new diagnostic strategies. Observer variations in lung scintigraphy interpretation when applying the PIOPED criteria were tested in 2 studies with 2 and 3 observers respectively and expressed as kappa values. The ability to improve agreement in lung scintigraphy interpretation was tested by training 2 observers from different hospitals. The impact of 3 observers' variations in lung scintigraphy interpretation when compared to pulmonary angiography, was tested by comparing the ROC areas of the observers. The value of combining subjectively derived numerical probabilities and the PIOPED categorical probabilities in lung scintigraphy reporting was compared to using the PIOPED categorization only, and this was tested by comparing ROC areas. The sensitivity and specificity of detecting an embolic source in the deep veins of the legs by ultrasound as a sign of PE when lung scintigraphy is inconclusive, was tested by comparison with pulmonary angiography. The sensitivity and specificity of spiral CT, compared to pulmonary angiography, was tested by comparison to pulmonary angiography. The inter- and intra-observer kappa values were in the range of moderate and fair. It was not possible to achieve better kappa values after training. Although observer variations were substantial, the accuracy did not differ significantly between the 3 observers. Incoorporating subjectively derived probabilities into lung scan reporting could not reduce the number of inconclusive investigations. Sensitivity and specificity of ultrasound in detecting PE was 0.70 and 0.97, respectively. However, 2 patients (of 9) had deep venous thrombosis and no pulmonary emboli at angiography. The sensitivity and specificity of spiral CT was 0.90 and 0.96, respectively. The observer variations at lung scintigraphy are substantial and may be difficult to improve between hospitals, even though the accuracy of observers in general is good. Although subjectively derived interpretation criteria did not show to be useful when added to categorical interpretation criteria, they may be useful when substituting established criteria. Despite recent progress in refining interpretation criteria, a substantial fraction of the patients still need pulmonary angiography to be performed. However, in many patients pulmonary angiography is not performed as prescribed. Spiral CT and ultrasound of the legs is a new favourable diagnostic strategy with a high validity in detecting venous thromboembolic disease, and a good availability and cost-effectiveness.

Acute Disease↗