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Biomedical subjects

J A Hansen

Publications and source records attributed to J A Hansen.

At least 19 recordsLinked to original sources
PubMed2003

Inheritable variable sizes of DNA stretches in the human MHC: conserved extended haplotypes and their fragments or blocks.

The difference in sizes of conserved stretches of DNA sequence within the major histocompatibility complex (MHC) in human individuals constitutes an underappreciated genetic diversity that has many practical implications. We developed a model to describe the variable sizes of stretches of conserved DNA in the MHC using the known frequencies of four different kinds of small (< 0.2 Mb) blocks of relatively conserved DNA sequence: HLA-Cw/B; TNF; complotype; and HLA-DR/DQ. Each of these small blocks is composed of two or more alleles of closely linked loci inherited as one genetic unit. We updated the concept of the conserved extended haplotype (CEH) using HLA allele identification and TNF microsatellites to show that specific combinations of the four blocks form single genetic units (>/= 1.5 Mb) with a total haplotype frequency in the Caucasian population of 0.30. Some CEHs extend to the HLA-A and -DPB1 loci forming fixed genetic units of up to at least 3.2 Mb of DNA. Finally, intermediate fragments of CEHs also exist, which are, nevertheless, larger than any of the four small blocks. This complexity of genetic fixity at various levels should be taken into account in studies of genetic disease association, immune response control, and human diversity. This knowledge could also be used for matching CEHs and their fragments for patients undergoing allotransplantation.

Alleles↗
PubMed2003

Tissue typing in support of unrelated hematopoietic cell transplantation.

The success of unrelated hematopoietic cell transplantation (HCT) for the treatment of hematologic malignancies has closely paralleled development of robust typing methods for comprehensive and precise donor-recipient matching. The application of molecular methods in clinical research has led to a more complete understanding of the immunogenetic barriers involving host-vs-graft (HVG) and graft-vs-host (GVH) reactions. Along with the development of less toxic transplant regimens, advances in the prevention and treatment of graft-vs-host disease (GVHD) and in the supportive care of the transplant recipient, improved HLA matching of potential unrelated donors has led to clinical results that begin to compare favorably with that of HLA-identical sibling transplants.

Alleles↗
PubMed2003

Hydrogenated dietary fat improves pork quality of pigs from two lean genotypes.

Pork quality is influenced by nutrition, genetics, management, and pork-processing procedures. Pigs of lean genotype fed diets high in unsaturated fat may have thinner, lower-quality bellies with a soft fat composition. Therefore, we investigated the effects of supplementing 5% choice white grease that had been chemically hydrogenated to iodine values of 80, 60, 40, or 20 on pork quality. Diets were fed to barrows and gilts of two genotypes (NPD [Ham-line x Manor hybrid] and PIC [406, 419, or 420 x C22]; n = 240) in a 4 x 2 x 2 factorial design. Pigs (76.8 kg of mean initial weight) were placed on test at a common age and were fed dietary treatments for 52 d. Pigs of PIC genotype were heavier at trial initiation, had higher feed intake and feed conversion ratio (F/G; P < 0.05), and greater backfat (26.3 vs. 24.0 mm; P < 0.001) and loin depth (59.0 vs. 55.3 mm; P < 0.001) compared with the NPD genotype pigs. As the iodine value of dietary fat was reduced, belly thickness increased (P < 0.05) and length decreased linearly (P < 0.05). Congruently, belly fat iodine value decreased from 73.9 to 67.4 (linear effect; P < 0.001) and belly fat C18:2 concentration declined from 20.6 to 16.3% (linear and quadratic effect; P < 0.001). The belly mono- and polyunsaturated fat ratio increased 29% as diet iodine value declined from 80 to 20 (linear and quadratic effect; P < 0.001). Further, there was a linear increase (P < 0.001) in saturated fatty acid concentration of belly fat (C14:0, C16:0, and C18:0) as dietary fat iodine value declined. Quadratic (P < 0.005) effects were detected in the level of C18:1trans as iodine value decreased from 80 to 20, paralleling dietary content. Dietary fat iodine value did not affect fat digestibility, ADFI, or F/G. Pork belly quality was improved as defined by reduced iodine value, C18:2 content, increased saturated fatty acid content, increased thickness, and decreased length as dietary iodine value decreased. Results indicate that reduction of dietary fat iodine value by chemical hydrogenation has the desirable effect of improving pork quality and does not alter growth performance.

Abdomen↗
PubMed2002

The effects of long-term cadmium exposure on the growth and survival of juvenile bull trout (Salvelinus confluentus).

Bull trout (Salvelinus confluentus) have been listed recently as threatened in the United States under the federal Endangered Species Act. This species currently resides, or historically resided, in several waterways that either are impacted or are under threat of impact from metals mining activities. We conducted a 55-day sub-chronic (i.e. sublethal) cadmium (Cd) exposure in water at 30 mg l(-1) (as CaCO(3)) hardness, pH 7.5, and 8 degrees C. Exposures were conducted using six replicate exposure tanks for each of the six treatments (five Cd concentrations and one control). Measured Cd concentrations were <0.013 (control), 0.052, 0.089, 0.197, 0.383, and 0.786 microg Cd l(-1). Exposure to 0.786 microg Cd l(-1) caused increased mortality (37%) and reduced growth (28% reduction in weight change) in fish exposed for 55 days. All Cd exposure concentrations caused significant whole body accumulation of Cd compared with controls. Our results indicate that even though fish are significantly accumulating Cd in each non-control treatment, growth reductions in bull trout occurred only at Cd concentrations that also caused significant mortality. The Cd concentration that reduced growth and survival in this long-term exposure (0.786 microg Cd l(-1)) is greater than the recently-revised US federal aquatic life criteria (ALC) value for the corresponding hardness concentration (ALC=0.62 microg Cd l(-1) for acute effects and 0.11 microg Cd l(-1) for chronic effects).

Animals↗
PubMed2002

Relationship between exposure duration, tissue residues, growth, and mortality in rainbow trout (Oncorhynchus mykiss) juveniles sub-chronically exposed to copper.

We conducted a 56-day sub-chronic test on the effects of Cu on rainbow trout (Oncorhynchus mykiss) fry at a nominal water hardness of 100 mg l(-1) (as CaCO(3)). Response measures were growth, whole body Cu concentrations, and mortality. Significant mortality was observed in fish exposed to 54.1 microg Cu l(-1) (47.8%) and 35.7 microg Cu l(-1) (11.7%). Growth was dose-dependent over the range of Cu treatments (0-54 microg Cu l(-1)), and was modeled as a function of Cu exposure concentration and exposure duration. Calculated inhibition concentrations (based on change in wet weight through a 56-day Cu exposure) were IC(50)=54.0 microg Cu l(-1), IC(20)=21.6 microg Cu l(-1), IC(10)=10.8 microg Cu l(-1), and IC(01)=1.1 microg Cu l(-1). Measured whole body Cu was also dose-dependent, and growth of trout fry was readily modeled as a function of tissue Cu and exposure duration. This model was virtually identical to a model previously developed for rainbow trout exposed to Cu at a hardness of 25 mg l(-1). Following the 56-day exposure period, we performed a 96-h acute challenge to Cu and Cd to evaluate the effects of Cu acclimation on acute Cu and Cd toxicity. Sensitivity to Cu was dependent on the 'acclimation dose'; trout previously held in control aquaria (i.e. not acclimated to Cu) suffered over 80% mortality, whereas trout previously exposed to 35.7 microg Cu l(-1) for 56 day suffered 20% mortality. These fish also showed somewhat reduced sensitivity to Cd, suggesting acclimation to Cu can enhance tolerance to other metals. Finally, the relationship between growth response and hardness (derived from several studies) appeared to have a different slope than the hardness relationship previously observed for lethality responses.

Adaptation, Physiological↗
PubMed2002

Simultaneous genotyping of single nucleotide polymorphisms in the IL-6, IL-10, TNFalpha and TNFbeta genes.

Single nucleotide polymorphisms (SNP) in the human IL-6, IL-10, TNFalpha and TNFbeta genes have been associated with gene function and susceptibility to disease. In this study, primers containing mismatches at 1-3 nucleotide positions were designed to incorporate a new restriction site recognized by endonucleases AlwNI, BcgI, BglI, BsaBI, BslI, BstXI, EcoNI or XcmI for genotyping SNPs in the IL-6 gene (position - 174), IL-10 gene (positions -592 and -1082), TNFalpha gene (positions -238, - 308 and -863) and TNFbeta gene (position + 249) by mismatched polymerase chain reaction and restriction fragment length polymorphism (PCR/RFLP). Our results show that appropriately designed BslI-based mismatched PCR/RFLP assays can be successfully used to determine the genotypes for approximately 40% of SNPs. The mismatched PCR strategy can be coupled with multiplex-amplification to enable simple and rapid determination of several SNP genotypes in a single reaction.

Cytokines↗
PubMed2002

Efficient cloning and expression of HLA class I cDNA in human B-lymphoblastoid cell lines.

Analysis of HLA restriction specificity is one of the important steps in characterizing T cell clones. This usually requires either a panel of HLA-typed cells or HLA cDNA transfectants. Although preparation of HLA cDNA transfectants is laborious, utilization of transfectants is advantageous when a suitable panel is not available due to linkage disequilibrium or rarity of the HLA allele of interest. In this report, we describe an efficient and rapid HLA cloning and expression system. Three sets of PCR primers specific for HLA-A, B and C loci were designed by extensively sequencing 5'- and 3'- untranslated regions of HLA class I genes. The PCR-amplified products were introduced into modified Phoenix retrovirus vectors containing a puromycin resistant gene under the control of a LTR promotor. Gibbon ape leukemia virus (GALV)-pseudotyped retrovirus was produced and infected into B-lymphoid cell lines. Following expansion in selection media, more than 80% of cells expressed transduced HLA at a comparable level to that normally expressed. These results indicate that locus-specific PCR cloning and utilization of GALV-pseudotyped retroviral vector can be an effective and relatively efficient tool for constructing a panel of different HLA transfectants.

Antibodies, Monoclonal↗
PubMed2002

The effects of dietary fat sources, levels, and feeding intervals on pork fatty acid composition.

Two experiments investigated the quantitative relationship between dietary fat and fatty acid composition of pork. Experiment 1 was designed to establish the rate of decline for linoleic acid and iodine value of pork fat during the late fattening phase following a dietary reduction. Gilts (n = 288) were fed diets varying in linoleic acid content from 4.11 to 1.56% for 4, 6, or 8 wk prior to slaughter. The maximum rate of decline was 2% 18:2 per week and 2.5 iodine value units per week. Experiment 2 evaluated the effects of dietary fat source and level on carcass fatty acid composition and on pork quality characteristics. Barrows (n = 147) and gilts (n = 147) were allocated to seven dietary treatments for the last 6 wk of the finishing phase. Diets contained 0, 2.5, or 5% dietary fat comprised of 100, 50, or 0% beef tallow. The balance was provided by animal-vegetable blended fat. As the level of tallow increased there was a linear decrease (P < 0.05) in 18:2 content and iodine value of carcass fat. Conversely, 16:1 and 18:1 increased linearly (P < 0.05) as tallow increased. However, 16:1 decreased linearly (P < 0.05) as level of fat increased. As the level of tallow was increased a greater reduction in 18:2 and iodine value was observed in diets with 5% dietary fat compared to diets with 2.5% fat (P < 0.05). These results indicate that reduction of dietary PUFA content had the desired effect of lowering 18:2 content and iodine value of pork fat and that significant alterations could be elicited in as little as 6 to 8 wk of feeding.

Adipose Tissue↗
PubMed2001

Major-histocompatibility-complex class I alleles and antigens in hematopoietic-cell transplantation.

BACKGROUND: Successful engraftment of hematopoietic stem cells from unrelated donors is influenced by disparities between the donor and recipient for HLA-A, B, and C alleles. Disparities between HLA sequence polymorphisms that are serologically detectable are termed antigen mismatches, whereas those that can be identified only by DNA-based typing methods are termed allele mismatches. Whether both kinds of polymorphisms are important in transplantation is not known. We tested the hypothesis that allele mismatches that are detectable only at the DNA level are less immunogenic than those that are serologically detectable and thereby are associated with a lower risk of graft failure after hematopoietic-cell transplantation METHODS: We used DNA sequencing to define the HLA-A, B, and C alleles in 471 patients who received bone marrow from unrelated donors for the treatment of chronic myeloid leukemia after myeloablative conditioning therapy. The odds ratios for graft failure were determined for recipients of transplants from donors with a single class I allele mismatch, a single class I antigen mismatch, or two or more class I mismatches, as compared with those with no mismatch RESULTS: A single HLA allele mismatch did not increase the risk of graft failure, whereas a single antigen mismatch significantly increased the risk. The risk was also increased if the recipient was HLA homozygous at the mismatched class I locus or if the donor had two or more class I mismatches CONCLUSIONS: HLA class I antigen mismatches that are serologically detectable confer an enhanced risk of graft failure after hematopoietic-cell transplantation. Transplants from donors with a single class I allele mismatch that is not serologically detectable may be used without an increased risk of graft failure.

Genes, MHC Class I↗
PubMed2001

[Posttraumatic hyphema induced by tossed frozen caramel candy].

The tossing of caramels is a traditional part of the celebrations on the last day of school. A case in which a 14-year-old boy suffered a secondary posttraumatic hyphaemia induced by a caramel tossed at the patient's left eye is described. The condition remitted spontaneously without loss of eyesight.

Adolescent↗
PubMed2001

Genomics of unrelated-donor hematopoietic cell transplantation.

Unrelated-donor hematopoietic cell transplantation is a proven curative modality for hematologic malignancies. The success of unrelated-donor transplantation has been achieved through a better understanding of the immunobiology of the HLA system and through more precise and comprehensive matching of donors and recipients. The extensive polymorphism of HLA genes confers important biological implications affecting engraftment, graft-versus-host disease and overall survival. Although more-complete HLA identity of the donor and recipient is associated with optimal transplant outcome, new information suggests that not every HLA disparity is functionally relevant. Future advances in unrelated-donor transplantation must include the identification of tolerable HLA mismatches, so that more patients may benefit from this therapeutic modality. Furthermore, the role of cytokine-gene polymorphisms and minor histocompatibility genes in transplant outcome requires investigation. Delineation of the function of these markers as transplantation determinants may provide alternative means for optimizing the results of hematopoietic cell transplantation.

Animals↗
PubMed2001

HLA-DRB1 and -DQB1 alleles in the Brazilian population of the northeastern region of the state of São Paulo.

The HLA-DRB1 and -DQB1 alleles in 161 healthy unrelated individuals, including Caucasians, Blacks and Mulattos (mixed Caucasian and Black), from the Northeastern region of the state of São Paulo, Brazil were analysed. The 36 different DRB1 alleles detected included not only common Caucasian alleles, but also DRB1*0411, 0807 and 1402, typical of Amerindians, and DRB1*0302, 1503, and 0804, typical of African American Blacks.

Alleles↗
PubMed2001

Single nucleotide polymorphisms in intron 2 of the human interleukin-1 receptor antagonist (IL-1Ra) gene: further definition of the IL-1 beta and IL-1Ra polymorphisms in North American Caucasians and Taiwanese Chinese.

Previous studies have suggested that a variable number tandem repeat (VNTR) polymorphism in the second intron of the interleukin-1 receptor antagonist (IL-1Ra) gene and the single nucleotide polymorphisms at positions -511 and +3954 of the IL-1beta gene might be associated with increased risks of chronic inflammatory diseases, autoimmune diseases and gastric cancer. In the present study, IL-1beta and IL-1Ra genotypes were analyzed among Asians in Taiwan and Caucasians in North America. We identified a novel polymorphism with 3 nucleotide substitutions in the IL-1Ra VNTR 2-repeat allele. One of the substitutions corresponds with the fourth 3' end nucleotide of the reverse primer that is often used for analysis of the IL-1Ra-associated VNTR locus. Mismatching between this primer and the 2-repeat allele can cause misleading amplification results when stringent conditions are used for annealing. The estimated haplotype frequencies of the variant IL-1 genes were significantly different between Taiwanese and Caucasians. The frequency of the pro-inflammatory IL-1Ra 2-repeat allele was significantly lower in Taiwanese than in Caucasians. In contrast, the frequencies of the pro-inflammatory IL-1beta -511T allele and +3954C allele were significantly higher among Taiwanese compared with Caucasians.

Asian People↗
PubMed2001

The biological significance of HLA-DP gene variation in haematopoietic cell transplantation.

Although it has been over 25 years since HLA-DP was mapped to the major histocompatibility complex (MHC), its biological functions remain ill-defined. We sought to test the hypothesis that HLA-DP functions in a manner similar to that of other class II genes by measuring the risk of clinically severe grades III-IV acute graft-vs.-host disease (GVHD) associated with recipient HLA-DP disparity after haematopoietic cell transplantation. HLA-DPB1 exon 2 was sequenced in 205 patients who underwent transplantation from HLA-A, -B, -C, -DRB1 and -DQB1 allele-matched unrelated donors. HLA-DPB1 mismatched recipients experienced a significantly increased risk of acute GVHD compared with HLA-DP-identical transplants. Patients who were mismatched for a single HLA-DPB1 allele had an odds ratio (OR) of 1.0 (0.5, 2.2; P = 0.99) and patients who were mismatched for two alleles had an OR of 2.2 (1.0, 4.9; P = 0.06) for developing acute GVHD. Compared with matched and single-allele mismatched transplants, patients who were mismatched for two DPB1 alleles had an OR of 2.2 (1.2, 4.1; P = 0.01). HLA-DP plays an important role in the alloimmune response. A threshold effect of multiple HLA-DP disparities is evident in determining the risk of acute GVHD after haematopoietic cell transplantation from unrelated donors.

Adolescent↗